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1

Bhattacharya, Indroneel, Neepamanjari Barman, and Ranu Sarkar. "Ki67 Protein expression and correlation with the histological grade and pTNM stage of colorectal carcinoma." Panacea Journal of Medical Sciences 11, no. 2 (August 15, 2021): 204–8. http://dx.doi.org/10.18231/j.pjms.2021.044.

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: Colorectal cancer, is third most frequently encountered malignancy worldwide. Histological grade, stage, and proliferative index act as vital prognostic markers, playing a decisive role in patient care and prognosis. While histopathological examination can determine grade and stage, Ki67 protein expression by immunohistochemistry represents the proliferative capacity of the malignant cell population. : This Study was conducted to immunohistochemically analyze expression of Ki67 protein and its change with respect to different grades and stage of colorectal adenocarcinoma. : A total of 66 histologically diagnosed cases of colorectal carcinoma underwent histopathological examination followed by immunohistochemistry for Ki67 protein. : A statistically significant (p=0.04) correlation was obtained between Ki67 labelling index and histopathological grade, with higher values of Ki67 labelling index in poorly differentiated carcinomas (43.2±1.7). The Ki67 labelling index value was lowest in stage IV disease (11.4±2.4) with metastatic burden, with higher values in lower stage diseases, however this correlation was not found to be significant statistically (p=0.07). : The rate of cell division and proliferation measured by Ki-67 antibody is related to histological grade of the malignancy, demonstrating higher mitotic activity with loss of differentiation and anaplasia. Stage IV disease have lower mitotic activity, thus may be less amenable to cytostatic chemotherapy drugs, and require multimodality treatment with addition of radiotherapy and other drug regimes.
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Moore, H. C., K. M. Wood, M. S. Jackson, M. A. Lastowska, D. Hall, H. Imrie, C. P. F. Redfern, et al. "Histological profile of tumours from MYCN transgenic mice." Journal of Clinical Pathology 61, no. 10 (August 4, 2008): 1098–103. http://dx.doi.org/10.1136/jcp.2007.054627.

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Background:MYCN is the most commonly amplified gene in human neuroblastomas. This proto-oncogene has been overexpressed in a mouse model of the disease in order to explore the role of MYCN in this tumour.Aims:To report the histopathological features of neuroblastomas from MYCN transgenic mice.Methods:27 neuroblastomas from hemizygous transgenic mice and four tumours from homozygous mice were examined histologically; Ki67 and MYCN immunocytochemistry was performed in 24 tumours.Results:Tumours obtained from MYCN transgenic mice resembled human neuroblastomas, displaying many of the features associated with stroma-poor neuroblastoma, including heterogeneity of differentiation (but no overt ganglionic differentiation was seen), low levels of Schwannian stroma and a high mitosis karyorrhexis index. The tumours had a median Ki67 labelling index of 70%; all tumours expressed MYCN with a median labelling index of 68%. The most striking difference between the murine and human neuroblastomas was the presence of tingible body macrophages in the transgenic mouse tumours reflecting high levels of apoptosis. This has not previously been described in human or other murine neuroblastoma models.Conclusions:These studies highlight the histological similarities between tumours from MYCN transgenic mice and human neuroblastomas, and reaffirm their role as a valuable model to study the biology of aggressive human neuroblastoma.
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Verma, Kavita, Satya Raj Negi, and Sanjay Garhwal. "To study histopathological features, GFAP staining and Ki 67/ MIB-1 labelling index in diagnoses and histological grading of gliomas." Indian Journal of Forensic and Community Medicine 8, no. 2 (July 15, 2021): 115–19. http://dx.doi.org/10.18231/j.ijfcm.2021.023.

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: A group of tumors that develops in the brain and spinal cord is called glioma. Histologically gliomas are classified into astrocytoma, ependymoma, oligodendroglioma, brain stem glioma and oligoastrocytoma. The present study was conducted to study histological grading of gliomas and correlate it with patient’s age, sex, GFAP staining, role of the Ki-67/MIB-1 labelling indices (PIs). The present retrospective study was conducted on 50 biopsies received. All specimens were subjected to immunohistochemistory for GFAP and MIB-1 and correlated with WHO grading for glioma.: High incidence of glial tumours was seen in the 3 and 4 decade with slight male predominance (60%), with commonest site being frontal lobe. Glioblastomas (Grade IV) constitute the most common glial tumour. A statistically significant correlation was observed between GFAP staining and Ki-67/MIB-1 with histological grading.: The study can prove helpful in diagnosis and histological grading of gliomas and in planning treatment protocols and strategies.
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Erokhina, Maria V., Larisa N. Lepekha, Elena E. Voronezhskaya, Leonid P. Nezlin, Vadim G. Avdienko, and Atadzhan E. Ergeshov. "Application of Laser Scanning Confocal Microscopy for the Visualization of M. tuberculosis in Lung Tissue Samples with Weak Ziehl–Neelsen Staining." Journal of Clinical Medicine 8, no. 8 (August 7, 2019): 1185. http://dx.doi.org/10.3390/jcm8081185.

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One of the key requirements for the diagnosis of pulmonary tuberculosis is the identification of M. tuberculosis in tissue. In this paper, we present the advantages of specific fluorescent antibody labelling, combined with laser scanning confocal microscopy (LSCM), for the detection of M. tuberculosis in histological specimens of lung tissues. We demonstrate that the application of LSCM allows: (i) The automatic acquisition of images of the whole slice and, hence, the determination of regions for subsequent analysis; (ii) the acquisition of images of thick (20–40 μm) slices at high resolution; (iii) single bacteria identification; and (iv) 3D reconstruction, in order to obtain additional information about the distribution, size, and morphology of solitary M. tuberculosis; as well as their aggregates and colonies, in various regions of tuberculosis inflammation. LSCM allows for the discrimination of the non-specific fluorescence of bacteria-like particles and their aggregates presented in histological lung samples, from the specific fluorescence of labelled M. tuberculosis, using spectrum emission analysis. The applied method was effective in the identification of M. tuberculosis in lung histological samples with weak Ziehl–Neelsen staining. Altogether, combining immunofluorescent labelling with the application of LSCM visualization significantly increases the effectiveness of M. tuberculosis detection.
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MATTFELDT, T., S. ECKEL, F. FLEISCHER, and V. SCHMIDT. "Statistical analysis of labelling patterns of mammary carcinoma cell nuclei on histological sections." Journal of Microscopy 235, no. 1 (July 2009): 106–18. http://dx.doi.org/10.1111/j.1365-2818.2009.03187.x.

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6

Boulanger, Jenna J., William A. Staines, Véronique LeBlanc, Eve-Ling Khoo, Jacky Liang, and Claude Messier. "A simple histological technique to improve immunostaining when using DNA denaturation for BrdU labelling." Journal of Neuroscience Methods 259 (February 2016): 40–46. http://dx.doi.org/10.1016/j.jneumeth.2015.11.006.

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7

Strateva, M., and G. Penchev. "HISTOLOGICAL, PHYSICOCHEMICAL AND MICROBIOLOGICAL CHANGES IN FRESH AND FROZEN/THAWED FISH." BULGARIAN JOURNAL OF VETERINARY MEDICINE 23, no. 1 (2020): 69–80. http://dx.doi.org/10.15547/tjs.2020.01.012.

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The production and supply of fish as food is constantly growing worldwide. Various methods are applied to extend its shelf life, one of them being freezing. According to European Union legislation, the state of the food and its treatment must be indicated on the label. If the food had been frozen prior to marketing and then sold thawed, this information must be provided to the consumer by labelling it. Otherwise, this is considered a fraud to the consumer since freezing significantly degrades the quality of fish. Histological, physicochemical and microbiological changes in the muscle tissue of frozen fish occur. Different methods may be applied to distinguish between fresh and frozen and them thawed fish, of which histological examination is a reliable method.
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8

Liu, Y., G. Chen, Y. S. Liu, Z. Q. Wang, T. Zhu, and F. Qiao. "Distraction osteogenesis correction for tissue defects of cleft palate: histological, immunohistochemical and fluorescent labelling study." International Journal of Oral and Maxillofacial Surgery 38, no. 5 (May 2009): 456–57. http://dx.doi.org/10.1016/j.ijom.2009.03.216.

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9

Yahaya, B., G. McLachlan, and D. D. S. Collie. "BrdU Pulse LabellingIn Vivoto Characterise Cell Proliferation during Regeneration and Repair following Injury to the Airway Wall in Sheep." Scientific World Journal 2013 (2013): 1–5. http://dx.doi.org/10.1155/2013/871932.

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The response of S-phase cells labelled with bromodeoxyuridine (BrdU) in sheep airways undergoing repair in response to endobronchial brush biopsy was investigated in this study. Separate sites within the airway tree of anaesthetised sheep were biopsied at intervals prior to pulse labelling with BrdU, which was administered one hour prior to euthanasia. Both brushed and spatially disparate unbrushed (control) sites were carefully mapped, dissected, and processed to facilitate histological analysis of BrdU labelling. Our study indicated that the number and location of BrdU-labelled cells varied according to the age of the repairing injury. There was little evidence of cell proliferation in either control airway tissues or airway tissues examined six hours after injury. However, by days 1 and 3, BrdU-labelled cells were increased in number in the airway wall, both at the damaged site and in the regions flanking either side of the injury. Thereafter, cell proliferative activity largely declined by day 7 after injury, when consistent evidence of remodelling in the airway wall could be appreciated. This study successfully demonstrated the effectiveness ofin vivopulse labelling in tracking cell proliferation during repair which has a potential value in exploring the therapeutic utility of stem cell approaches in relevant lung disease models.
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Schatzker, J., G. Sumner-Smith, V. L. Fornasier, and J. R. Cockshutt. "Biological Fixation of a Porous-Coated, Metal-Backed Acetabular Component in Canine Total Hip Arthroplasty." Veterinary and Comparative Orthopaedics and Traumatology 01, no. 03/04 (October 1988): 141–45. http://dx.doi.org/10.1055/s-0038-1633277.

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A total hip surface replacement was successfully performed on eight adult dogs, using a porous-coated, cobalt-chromium- molybdenum alloy acetabular resurfacing component fixed to the acetabulum with 3.5 mm cortical screws. Functional, radiological, histological and fluorochrome labelling studies were used to assess tissue response to the implant. At four months after implantation, seven of the acetabular components were anchored with well organized fibrous tissue. Bone ingrowth had occurred in three components. Failures appeared to be due to technical difficulties encountered during the surgical procedure.
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11

Jankowski, J., R. McMenemin, D. Hopwood, J. Penston, and K. G. Wormsley. "Abnormal expression of growth regulatory factors in Barrett's oesophagus." Clinical Science 81, no. 5 (November 1, 1991): 663–68. http://dx.doi.org/10.1042/cs0810663.

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1. In order to assess potential abnormalities in the control of mucosal proliferation, 30 patients with Barrett's oesophagus were studied in order to evaluate the presence and distribution of epidermal growth factor, transforming growth factor-α and epidermal growth factor receptor to determine the Ki-67 labelling index in the affected oesophageal mucosa. Serial sections were analysed immunohistochemically. Ten of the patients had adenocarcinoma in the Barrett's mucosa and the other 20 had differing histological types of Barrett's mucosa (10, intestinal-type; 10, fundic-or cardiac-type). 2. The expression of transforming growth factor-α, epidermal growth factor and epidermal growth factor receptor was increased and the Ki-67 labelling index was higher in Barrett's mucosa compared with normal gastric mucosa. The ‘intestinal-type’ of Barrett's mucosa had the greatest expression of transforming growth factor-α, epidermal growth factor receptor and the highest Ki-67 labelling index compared with the other types of Barrett's metaplasia. Five cases of ‘intestinal-type’ Barrett's metaplasia had especially high Ki-67 labelling indices and these patients over-expressed both transforming growth factor-α and epidermal growth factor receptor. The patients with adenocarcinomas in the Barrett's mucosa also over-expressed transforming growth factor-α and epidermal growth factor receptor, but not epidermal growth factor, compared with normal gastric mucosa. 3. In conclusion, both normal gastric mucosa and Barrett's mucosa have potential autocrine growth regulatory mechanisms, but Barrett's mucosa has increased expression of both of the measured ligands and of the epidermal growth factor receptor.
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Ganesan, Sarumathy, Prathiba Arumugam, Nithya Ilanchezhian, and Saraswathi Manickam. "Evaluation of Ki67 Expression in Relation to Tumor Stage and Fuhrman Nuclear Grade of Renal Cell Carcinoma and MUC1 Expression in Clear Cell Renal Cell Carcinoma." Journal of Evolution of Medical and Dental Sciences 10, no. 33 (August 16, 2021): 2718–22. http://dx.doi.org/10.14260/jemds/2021/555.

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BACKGROUND Renal cell carcinoma (RCC) is the most common malignant renal tumour in adults. Prognosis of RCC depends on various factors like tumour stage, nuclear grade and histological type. For planning adjuvant therapy, accurate prediction of prognosis is mandatory. In many studies, ki67 and MUC1 has shown to be of prognostic significance and immunohistochemical expression of these two markers plays an important role in determining the prognosis of RCC. The purpose of this study was to evaluate the Ki67 expression in histologically confirmed cases of RCC and MUC1 expression in clear cell renal cell carcinoma, and to correlate them with the stage and Fuhrman nuclear grade of the tumour, in order to determine their role as prognostic markers in RCC. METHODS This study was a retrospective study. A total of 50 specimens of renal cell carcinoma were studied. The specimens were total and partial nephrectomy done in the department of urology for a period of 3 years. Expression of Ki67 and MUC1 in RCC were studied by immunohistochemistry (IHC). Statistical analysis was performed and P value < 0.05 was considered significant. RESULTS Out of 50 RCC studied, Ki67 labelling index ≥ 15 % was found in 35 cases. For MUC1, immunoreactivity of more than 10 % of tumor cell was found in 28/34 of clear cell RCC. In this study, Ki67 labelling index showed statistically significant expression with the stage of tumor and the nuclear grade. MUC1 expression also showed significant correlation with nuclear grade and stage of clear cell RCC. CONCLUSIONS High Ki67 labelling index in renal cell carcinoma is seen to correlate with higher nuclear grade and stage of tumor. High level expression with circumferential staining pattern of MUC1 is seen in high grade tumours with increased risk of metastasis. So MUC1 and Ki67 can be considered as a marker of prognosis of RCC. KEY WORDS Renal Cell Carcinoma, Immunohistochemistry, Ki67, MUC1
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13

ARNER, M., K. JONSSON, and P. ASPENBERG. "Complete Palmar Dislocation of the Lunate in Rheumatoid Arthritis." Journal of Hand Surgery 21, no. 3 (June 1996): 384–87. http://dx.doi.org/10.1016/s0266-7681(05)80210-4.

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We report a case of complete palmar dislocation of the lunate in a rheumatoid patient. X-rays showed a normal bone structure of the lunate without sclerosis or collapse and on MRI an almost normal signal intensity was found. The lunate was removed. Histological examination showed complete necrosis of both marrow and bone cells, and tetracycline labelling showed no fluorescence. This case illustrates that neither X-ray nor magnetic resonance imaging (MRI) can detect complete bone necrosis. When X-ray or MRI changes do occur, these are indications of cellular events following some degree of spontaneous revascularization.
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Aschoff, A., M. Jantz, and G. Jirikowski. "In-Situ End Labelling with Bromodeoxyuridine - an Advanced Technique for the Visualization of Apoptotic Cells in Histological Specimens." Hormone and Metabolic Research 28, no. 07 (July 1996): 311–14. http://dx.doi.org/10.1055/s-2007-979801.

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Lu, Y., J. Xiong, B. Yin, J. Wen, L. Liu, and D. Geng. "The role of three-dimensional pseudo-continuous arterial spin labelling in grading and differentiating histological subgroups of meningiomas." Clinical Radiology 73, no. 2 (February 2018): 176–84. http://dx.doi.org/10.1016/j.crad.2017.08.005.

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16

Madar, M., M. Slizova, J. Czerwinski, G. Hrckova, D. Mudronova, S. Gancarcikova, M. Popper, J. Pistl, J. Soltys, and R. Nemcova. "Histo-FISH protocol to detect bacterial compositions and biofilms formation in vivo." Beneficial Microbes 6, no. 6 (December 1, 2015): 899–907. http://dx.doi.org/10.3920/bm2015.0016.

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The study of biofilm function in vivo in various niches of the gastrointestinal tract (GIT) is rather limited. It is more frequently used in in vitro approaches, as an alternative to the studies focused on formation mechanisms and function of biofilms, which do not represent the actual in vivo complexity of microbial structures. Additionally, in vitro tests can sometimes lead to unreliable results. The goal of this study was to develop a simple approach to detect bacterial populations, particularly Lactobacillus and Bifidobacterium in biofilms, in vivo by the fluorescent in situ hybridisation (FISH) method. We standardised a new Histo-FISH method based on specific fluorochrome labelling probes which are able to detect Lactobacillus spp. and Bifidobacterium spp. within biofilms on the mucosal surface of the GIT embedded in paraffin in histological slices. This method is also suitable for visualisation of bacterial populations in the GIT internal content. Depending on the labelling probes, the Histo-FISH method has the potential to detect other probiotic strains or pathogenic bacteria. This original approach permits us to analyse bacterial colonisation processes as well as biofilm formation in stomach and caecum of BALB/c and germ-free mice.
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Barratt, Olivia, Melanie Simms, Miriam John, Michael Lewis, and Phil Atkin. "Improving diagnostic specimen management systems in an oral medicine department." BMJ Open Quality 9, no. 3 (July 2020): e000926. http://dx.doi.org/10.1136/bmjoq-2020-000926.

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Histological, haematological and microbiological investigations are essential in the field of oral medicine and are a crucial adjunct to clinical findings, often being relied on to obtain a definitive diagnosis. Importantly, in some cases, these investigations can help exclude or confirm the presence of malignancy. This project highlighted some problems regarding labelling and recording of specimens in an oral medicine department and a lack of clear specimen management processes. It aimed to improve specimen management by reducing reported incidents surrounding diagnostic tests. Quality improvement methods such as process mapping were key to understanding the journey of specimens and the departments involved at each stage of the system. Initiatives included a recording log book, staff training, information signage around the clinic and delegation of responsibilities, all of which were implemented over multiple plan, do, study, act (PDSA) cycles. The project was extremely successful and since implementation there has been a clear and sustained reduction in reported incidents. The small number of incidents which did occur all involved transportation of specimens and none involved labelling or recording. One can conclude that the change in test management systems in terms of recording and labelling of specimens in the department has been sustained. Ongoing engagement with stakeholders and senior leaders is the priority to ensure further reduction in incidents in the future and that the improvements are maintained. This project demonstrates how simple, realistic, cost-effective, quality improvement initiatives can have a significant positive impact on patient care and hospital management systems.
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Qiao, Huilian, He Ma, Wanjun Cao, Hao Chen, Jinhua Wei, and Zhen Li. "Protective effects of polydatin on experimental testicular torsion and detorsion injury in rats." Reproduction, Fertility and Development 29, no. 12 (2017): 2367. http://dx.doi.org/10.1071/rd17046.

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Oxidative stress plays a critical role in the process of testicular torsion and detorsion (T/D). The purpose of the present study was to investigate the protective effect of polydatin (PD) on testicular T/D injury. Rats were randomly divided into three groups, a sham group, a group subjected to 2 h torsion followed by 24 h detorsion and a group subjected to T/D and injected i.p. with 20 mg kg−1 PD 30 min before detorsion. Unilateral orchiectomy was performed after 24 h of reperfusion. Half the testes were prepared for histological examination by haematoxylin–eosin staining and the terminal deoxyribonucleotidyl transferase-mediated dUTP–digoxigenin nick end-labelling (TUNEL) technique. In the remaining tissues, levels of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were determined, as was the expression of several apoptosis-related proteins. Compared with the T/D group, PD pretreatment significantly ameliorated the morphological damage, lowered the Cosentino histological score and increased the mean number of germ cell layers and Johnsen’s testicular biopsy score. In addition, PD treatment markedly decreased MDA levels and upregulated CAT, GPx and SOD activity. Furthermore, PD decreased T/D-induced germ cell-specific apoptosis, attenuated the activation of caspase-3, caspase-8, caspase-9 and poly(ADP-ribose) polymerase and increased the Bcl-2/Bax ratio. The findings indicate that PD has a protective effect against testicular T/D injuries, especially at the histological, antioxidative stress and antiapoptotic levels.
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Nagamine, Takeaki, Keiji Suzuki, T. Kondo, Kyoumi Nakazato, Satoru Kakizaki, Hitoshi Takagi, and Katsuyuki Nakajima. "Interferon-Alpha-Induced Changes in Metallothionein Expression in Liver Biopsies from Patients with Chronic Hepatitis C." Canadian Journal of Gastroenterology 19, no. 8 (2005): 481–86. http://dx.doi.org/10.1155/2005/262597.

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An association between reactive oxygen species and liver damage has been postulated in the course of hepatitis C virus (HCV) infection. Metallothionein (MT), induced by HCV core protein and interferon (IFN), plays a role in scavenging free radicals. MT expression in liver biopsies obtained from 21 patients with chronic HCV infection before and after IFN-alpha therapy was investigated. Changes in Knodell histological activity index (HAI) scores, MT protein levels (immunohistochemistry), MT-I and MT-II messenger (m)RNA expression levels (in situ hybridization) and proliferating cell nuclear antigen (PCNA) labelling index were determined and compared in serial liver specimens. MT staining was clustered around the portal tracts with inflammatory cells and fibrosis. The pattern of MT protein before IFN-alpha therapy was similar in all patients, but was higher in IFN-sustained responders than in nonresponders after IFN-alpha therapy. HAI scores and PCNA labelling indexes were significantly reduced after IFN-alpha therapy. MT-II mRNA expression correlated positively with PCNA index before therapy and with HAI scores after therapy ( P<0.05). No correlation was found between MT-I mRNA and HAI scores or PCNA index. The findings indicate that IFN-alpha-induced hepatic MT may participate in the therapeutic effects of IFN-alpha for HCV. In addition, MT-II mRNA expression may be involved in cell proliferation in the livers of patients with chronic HCV infection.
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Di Leo, Milena, Laura Poliani, Daoud Rahal, Francesco Auriemma, Andrea Anderloni, Cristina Ridolfi, Paola Spaggiari, et al. "Pancreatic Neuroendocrine Tumours: The Role of Endoscopic Ultrasound Biopsy in Diagnosis and Grading Based on the WHO 2017 Classification." Digestive Diseases 37, no. 4 (2019): 325–33. http://dx.doi.org/10.1159/000499172.

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Background: One of the controversial issues in the diagnosis of pancreatic neuroendocrine tumours (pNETs) is the accurate prediction of their clinical behaviour. Objectives: The aim of the study was to evaluate the role of endoscopic ultrasound (EUS) biopsy in the diagnosis and grading of pNETs in a certified ENETS Center. Methods: A prospectively maintained database of EUS biopsy procedures was retrospectively reviewed to identify all consecutive patients referred to a certified ENETS Center with a suspicion of pNET between June 2014 and April 2017. The cytological and/or histological specimens were stained and the Ki-67 labeling index was evaluated. In patients undergoing surgery, the grade obtained with EUS-guided biopsy was compared with the final histological grade. The grade was evaluated according to the 2017 WHO classifications and grading. Results: The study population included 59 patients. EUS biopsy material reached an adequacy of 98.3% and was adequate for Ki-67 evaluation in 84.7% of cases. Twenty-nine patients (49.2%) underwent surgery. Of these, 25 patients had Ki-67 evaluated on EUS biopsy: the agreement between EUS biopsy grading and surgical specimen grading was 84%. Conclusion: EUS biopsy is an accurate method for the diagnosis and grading of pNETs based on the WHO 2017 Ki-67 labelling scheme.
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Yan, Fengcai, Feng Shi, Xinbao Li, Hong Chang, Mulan Jin, and Yan Li. "Prognostic significance of CEA, Ki67 and p53 in pseudomyxoma peritonei of appendiceal origin." Journal of International Medical Research 49, no. 6 (June 2021): 030006052110222. http://dx.doi.org/10.1177/03000605211022297.

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Objective To determine the levels of carcinoembryonic antigen (CEA), proliferating nuclear antigen Ki67 and p53 in pseudomyxoma peritonei (PMP) of appendiceal origin and to correlate the levels with clinicopathological characteristics and overall survival. Methods This retrospective study collected data on clinicopathological features and immunohistochemical staining of CEA, Ki67 and p53 in patients with PMP of appendiceal origin. Overall survival was evaluated using Kaplan–Meier plots. Median survival time was estimated by Log-rank tests. Potential prognostic factors were evaluated by Cox proportional hazards regression models. Results A total of 141 patients with PMP of appendiceal origin were enrolled in the study with a median age of 54 years. Of these, 93 (66.0%) were diagnosed with low-grade mucinous carcinoma, 43 (30.5%) with high-grade mucinous carcinoma and five (3.5%) with high-grade with signet ring cells. CEA exhibited ubiquitous immunopositivity in most cases and was not associated with overall survival. Ki67 labelling index (LI) and p53 status were related to histological grade and overall survival. The main pathological indicators affecting survival included histological grade, lymph node involvement, angiolymphatic invasion, Ki67 LI and p53. Conclusion Combined analysis of high Ki67 LI and aberrant p53 may provide the basis for evaluating the biological behaviour of PMP and predicting clinical outcome.
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Wharton, S. B., K. K. Chan, J. R. Anderson, K. Stoeber, and G. H. Williams. "Replicative Mcm2 protein as a novel proliferation marker in oligodendrogliomas and its relationship to Ki67 labelling index, histological grade and prognosis." Neuropathology and Applied Neurobiology 27, no. 4 (August 2001): 305–13. http://dx.doi.org/10.1046/j.0305-1846.2001.00333.x.

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Degen, N., K. Brandle, and L. Peter. "Histological studies on the development of retinotectal projections from nasoventral quarter-eyes in Xenopus laevis." Development 118, no. 2 (June 1, 1993): 589–99. http://dx.doi.org/10.1242/dev.118.2.589.

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In Xenopus larvae, the size and location of the retinotectal projection of nasoventral quarter-eyes was analyzed in early stages (43–47), midlarval stages (50 and 53) and metamorphic stages (56 and 60), by labelling the optic nerve with the cobalt-lysine complex or with horseradish-peroxidase (HRP). For direct comparison, both fragment and normal eye projections were determined simultaneously in the same specimen in brain whole mounts. During early stages (up to stage 47), the projection fields of normal eyes and quarter-eyes are confined to the rostral part of the tectum. The extension of the projection in rostrocaudal direction of eye fragments does not differ from that of normal eyes. During later development up to metamorphosis, normal eyes expand their projection over the newly formed tectal surface in a caudal direction, whereas the fiber terminations of nasoventral quarter-eyes still remain in the rostral part of the tectum. Quantitative studies revealed that there is no difference in the size of both halves of the tectum. At least for quarter-eyes, however, a strict correlation between eye size and extension of the contralateral projection field could be established. According to our results, it is unlikely that during development local tectal markers are involved in determining the location of the projection field and the retinotopic ordering of the optic fibers. Instead we suggest that the optic fibers separate in accordance with their retinal specificity.
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S., Mithra, Archana Santhanam, Herald J. Sherlin, Gifrina Jayaraj, and Don K.R. "Diagnostic Utility of Ki-67 for Histopathological Typing of Conventional Ameloblastoma, Proliferative Ameloblastoma and Ameloblastic Carcinoma – A Retrospective Study." Journal of Evolution of Medical and Dental Sciences 10, no. 32 (August 9, 2021): 2592–96. http://dx.doi.org/10.14260/jemds/2021/531.

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BACKGROUND Ameloblastoma is a rare, benign odontogenic neoplasm which is locally aggressive and mostly present with a painless swelling. The enigma about the diagnosis of proliferative ameloblastoma and ameloblastic carcinoma is still a debate because the diagnostic criteria is not standardized or quantified which has a direct correlation on its biological behaviour and prognosis. Despite numerous studies, correlation between the histological patterns of ameloblastoma and tumour behaviour has not been consistently established. The present study was done to compare the expression levels of Ki-67 between conventional ameloblastoma, proliferative ameloblastoma and ameloblastic carcinoma and to assess the usefulness of these markers for diagnostic differentiation. METHODS A retrospective study of total of 18 cases of ameloblastoma were retrieved from the archives of Department of Oral and Maxillofacial Pathology, Saveetha Dental College from 2012 till 2019, which included conventional ameloblastoma, proliferative ameloblastoma and ameloblastic carcinoma. Immunohistochemical (IHC) analysis was done using the marker Ki-67 and labelling index were determined for the same. RESULTS The results of the current study showed that the cellular proliferative activity assessed using Ki-67 in follicular ameloblastoma was (55 %), 4 cases of plexiform ameloblastoma (22 %), 17 % of proliferative ameloblastoma and 6 % of ameloblastic carcinoma showed negative expression. CONCLUSIONS Immunophenotyping using the marker Ki-67 may be a useful tool for histological typing of ameloblastoma. KEY WORDS Ameloblastoma, Ki-67, IHC, Immunophenotyping
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JENSEN, V., M. HØYER, F. B. SØRENSEN, J. KELLER, and O. M. JENSEN. "MIB‐1 expression and iododeoxyuridine labelling in soft tissue sarcomas: an immunohistochemical study including correlations with p53, bcl‐2 and histological characteristics." Histopathology 28, no. 5 (May 1996): 437–44. http://dx.doi.org/10.1046/j.1365-2559.1996.333377.x.

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Merico, Valeria, Gabriela Diaz de Barboza, Chiara Vasco, Ruben Ponce, Valeria Rodriguez, Silvia Garagna, and Nori Tolosa de Talamoni. "A mitochondrial mechanism is involved in apoptosis of Robertsonian mouse male germ cells." REPRODUCTION 135, no. 6 (June 2008): 797–804. http://dx.doi.org/10.1530/rep-07-0466.

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The aim of this study was to determine whether the intrinsic mechanism of apoptosis is involved in the death of germ cells in Robertsonian (Rb) heterozygous adult male mice. Testes from 5-month-old Rb heterozygous CD1×Milano II mice were obtained and compared with those from homozygous CD1 (2n=40) and Milano II (2n=24) mice. For histological evaluation of apoptosis, TUNEL labelling and immunohistochemistry were used to localise Bax and cytochrome c. Expression of calbindin D28k (CB), an anti-apoptotic molecule, was also analysed by immunohistochemistry and immunoblotting. Testicular ultrastructure was visualised by electron microscopy. Morphology and cell associations were abnormal in the Rb heterozygous seminiferous epithelium. An intense apoptotic process was observed in tubules at stage XII, mainly in metaphase spermatocytes. Metaphase spermatocytes also showed Bax and cytochrome c redistributions. Mitochondria relocated close to the paranuclear region of spermatocytes. CB was mainly expressed in metaphase spermatocytes, but also in pachytene spermatocytes, spermatids and Sertoli cells at stage XII. The co-localisation of CB and TUNEL labelling was very limited. Sixty per cent of metaphase spermatocytes were apoptotic and calbindin negative, while 40% were calbindin positive without signs of apoptosis. Ten per cent of the Bax- and cytochrome c-positive cells were also calbindin positive. These data suggest that apoptosis of the germ cells in heterozygous mice occurs, at least in part, through a mitochondrial-dependent mechanism. Calbindin overexpression might prevent or reduce the apoptosis of germ cells caused by Rb heterozygosity, which could partially explain the subfertility of these mice.
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Ang, L. C., M. Plewes, L. Tan, H. Begley, A. Agranovich, and D. Shul. "Proliferating Cell Nuclear Antigen Expression in the Survival of Astrocytoma Patients." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 21, no. 4 (November 1994): 306–10. http://dx.doi.org/10.1017/s0317167100040877.

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Abstract:The PC 10, a monoclonal antibody against proliferating cell nuclear antigen (PCNA), is known to show immunoreactivity in routinely processed paraffin embedded tissue. This antibody was applied to 72 astrocytic tumours from surgical biopsy material obtained in a ten year period. The PCNA labelling index (LI) obtained by image analysis was compared with patient’s survival, age at diagnosis, and Karnofsky score as well as the histological grade of tumour. The survival analysis shows that patients with tumour PCNA LI of more than 6% have significantly poorer prognosis than those with 6% and below. In addition, there is also good correlation between PCNA LI with age, Karnofsky and tumour grade. This study suggests that although the PCNA expression of astrocytoma could be a useful predictor of patient’s outcome, it is not an independent prognostic factor but has derived its statistical association with survival secondarily through its relationship with tumour grade, age and Karnofsky score.
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Watanabe, Tatiane T. N., Laura L. de Almeida, Flademir Wouters, Angelica T. B. Wouters, Priscila Zlotowski, and David Driemeier. "Histopathological and immunohistochemical findings of swine with spontaneous influenza A infection in Brazil, 2009-2010." Pesquisa Veterinária Brasileira 32, no. 11 (November 2012): 1148–54. http://dx.doi.org/10.1590/s0100-736x2012001100013.

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Swine influenza (SI) is caused by the type A swine influenza virus (SIV). It is a highly contagious disease with a rapid course and recovery. The major clinical signs and symptoms are cough, fever, anorexia and poor performance. The disease has been associated with other co-infections in many countries, but not in Brazil, where, however, the first outbreak has been reported in 2011. The main aim of this study was to characterize the histological features in association with the immunohistochemical (IHC) results for influenza A (IA), porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) in lung samples from 60 pigs submitted to Setor de Patologia Veterinária at the Universidade Federal do Rio Grande do Sul (SPV-UFRGS), Brazil, during 2009-2010. All of these lung samples had changes characterized by interstitial pneumonia with necrotizing bronchiolitis, never observed previously in the evaluation of swine lungs in our laboratory routine. Pigs in this study had showed clinical signs of a respiratory infection. Swine samples originated from Rio Grande do Sul 31 (52%), Santa Catarina 14 (23%), Paraná 11 (18%), and Mato Grosso do Sul 4 (7%). Positive anti-IA IHC labelling was observed in 45% of the cases, which were associated with necrotizing bronchiolitis, atelectasis, purulent bronchopneumonia and hyperemia. Moreover, type II pneumocyte hyperplasia, alveolar and bronchiolar polyp-like structures, bronchus-associated lymphoid tissue (BALT) hyperplasia and pleuritis were the significant features in negative anti-IA IHC, which were also associated with chronic lesions. There were only two cases with positive anti-PCV2 IHC and none to PRRSV. Therefore, SIV was the predominant infectious agent in the lung samples studied. The viral antigen is often absent due to the rapid progress of SI, which may explain the negative IHC results for IA (55%); therefore, IHC should be performed at the beginning of the disease. This study has shown how important a careful histological evaluation is for the diagnosis. Since 2009, a new histological feature of swine pneumonia in animals with respiratory clinical signs has been observed in samples from pigs with clinical respiratory disease submitted to SPV-UFRGS. In addition, the results proved the importance of histological evaluation for swine herd health management.
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Voicu, Ioan Paul, Piero Chiacchiaretta, Massimo Caulo, Evelina Miele, Alessia Carboni, Andrea Carai, Francesca Diomedi-Camassei, et al. "IMG-19. RADIOMICS AND SUPERVISED DEEP LEARNING TO PREDICT MOLECULAR SUBGROUPS IN MEDULLOBLASTOMA BASED ON WHOLE TUMOR VOLUME LABELING: A SINGLE CENTER MULTIPARAMETRIC MR ANALYSIS." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii358—iii359. http://dx.doi.org/10.1093/neuonc/noaa222.354.

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Abstract PURPOSE Medulloblastoma (MB) is a complex pathology. Four molecular subgroups have been unveiled (Wingless-WNT, Sonic Hedgehog-SHH, Group 3-G3 and Group 4-G4), characterized by significant differences in patient clinical outcome. We investigated the utility of a radiomic analysis to predict molecular subgroups in patients with MB. MATERIALS AND METHODS We retrospectively evaluated 42 patients with histological diagnosis of MB, known molecular subgroup, and diagnostic MRI scan performed in our Institution on a 3 Tesla magnet. For each patient, FLAIR, ADC, T2 and contrast-enhanced MPRAGE sequences were analysed. Solid tumor volumes were segmented semiautomatically. 107 features were extracted for each sequence (Pyradiomics, Python). Features were tested for stability against labelling variations, selecting those presenting Intraclass Correlation Coefficient (ICC)&gt;0.9 across all labelling variations and all sequences. Among the remaining features, relevant features were selected with an all-relevant wrapper algorithm (Boruta, R). Remaining features were used to predict MB subgroup with a Random Forest algorithm(R). The most relevant features were ranked based on Gini index (R). RESULTS 83/107 features presented ICC &gt;0.9 for all sequences. Boruta selected 10 features. Classification analysis yielded an out-of-bag (OOB) error rate of 0.6%, (99.4% accuracy). The most relevant features for classification were “simple” first-order features such as volume, major axis or shape. CONCLUSION This radiomic study yielded robust features, which showed high accuracy in predicting the molecular MB subgroups. Random forest algorithms are ideal for multiclass classification (eg. MB subgroups) and are intrinsically suited against overfitting. The most relevant for molecular classification were first-order features.
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Stevanovic, Lidija, Matthias Choschzick, Linda Moskovszky, and Zsuzsanna Varga. "Variability of predictive markers (hormone receptors, Her2, Ki67) and intrinsic subtypes of breast cancer in four consecutive years 2015–2018." Journal of Cancer Research and Clinical Oncology 145, no. 12 (October 18, 2019): 2983–94. http://dx.doi.org/10.1007/s00432-019-03057-0.

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Abstract Purpose Accurate monitoring of predictive markers is of utmost importance as oncological treatment decisions almost entirely depend on these factors. In this study, we conducted a quality control assessment on hormone receptors, Her2 status, Ki67 Labelling Index (LI) and histological grading in breast cancer over 4 years (2015–2018). Methods Altogether 2214 consecutive breast cancer cases were included. Data on estrogen (ER) and progesterone receptors (PR), Her2 and Ki67, were available in all cases and were tested mostly on preoperative biopsies, in selected cases on postoperative surgical specimens. ER, PR, and Ki67 were assessed with immunohistochemistry (IHC), Her2 status with IHC and fluorescence in situ hybridization. Results ER/PR were positive in 74–79% cases, ER/PR/Her2 negative in 6.16–10.70% and Her2 positive in 11.49–13.88%/year. Ki67 had median values as 15–17.5% in ER/PR-positive cases, 55–60% in triple-negative cases and 30–32.50% in Her2-positive cases. Histological grading distribution for well (G1), moderately (G2) and poorly (G3) differentiated carcinomas was 15.8–19.1% for G1, 54.2–54.8% for G2 and 21.7–23.7% for G3 cases. Variation in yearly distributions was not significant in any of these markers. Conclusions Predictive markers displayed a yearly similar distribution in breast cancer cases independently of grading or of intrinsic subtypes. These results point to a qualitative high performance of predictive marker assessment in breast cancer, corresponding to expected on average positivity rate per marker and per year. It is recommended to monitor positivity rate of ER, PR, Ki67 and Her2 yearly or periodically to comply with quality assurance requirements.
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Sikka, K., S. C. Sharma, A. Thakar, and S. Dattagupta. "Evaluation of epithelial proliferation in paediatric and adult cholesteatomas using the Ki-67 proliferation marker." Journal of Laryngology & Otology 126, no. 5 (December 14, 2011): 460–63. http://dx.doi.org/10.1017/s002221511100315x.

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AbstractIntroduction:The aggressiveness of cholesteatoma in children compared with adults is well known. However, the factors influencing the poorer prognosis of paediatric cholesteatoma are not well understood. This study compared the proliferative potential of paediatric cholesteatoma with that of adult cholesteatoma, using Ki-67 as a proliferation marker.Methods:A prospective study of 67 patients with aural cholesteatoma was performed. Thirty-eight adult and 29 paediatric cases were evaluated using clinical parameters including bone erosion, complications and extent of disease. A surgical specimen underwent histological evaluation and measurement of the proliferation index using Ki-67 labelling. Normal epithelium from a control group was also examined.Results:Cholesteatoma epithelium has a greater rate of proliferation than normal skin. There were however no statistical differences between the paediatric and adult cholesteatoma groups in terms of clinical behaviour or proliferation potential. Paediatric cholesteatoma was similar to adult cholesteatoma in terms of complications, bone erosion and disease spread.Conclusion:Cholesteatoma is a disorder of epithelial proliferation. Although postulated to be more aggressive in children than adults, this study found no clinicopathological differences between paediatric and adult cases.
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ISHII, Akiko, and S. Hao LO. "A role of tensin in skeletal-muscle regeneration." Biochemical Journal 356, no. 3 (June 8, 2001): 737–45. http://dx.doi.org/10.1042/bj3560737.

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Regeneration of skeletal muscle requires the activation, proliferation, differentiation and fusion of satellite cells to generate new muscle fibres. This study was designed to determine the role of tensin in this process. Cardiotoxin was used to induce regeneration in the anterior tibial muscles of tensin-knockout and wild-type mice. From histological analysis, we found that the regeneration process lasted longer in knockout than in wild-type mice. To investigate the mechanism involved in this delay, we examined each regeneration step in animals and cultured primary cells. We found fewer proliferating myogenic cells identified by bromodeoxyuridine and desmin double labelling in knockout mice on the first 2 days after injury. Expression of myosin, paxillin, dystrophin and dystrophin-associated proteins were delayed in knockout mice. Withdrawal from the cell cycle was less efficient in isolated knockout myoblasts, and the fusion capacity was reduced in these cells as well. These defects in regeneration most likely contributed to the 9-fold increase of centrally nucleated fibres occurring in the non-injected knockout mice. Our results demonstrated clearly that tensin plays a role in skeletal-muscle regeneration.
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Kitamoto, J., K. Sakamoto, K. Ozaki, Y. Mishina, and K. Arikawa. "Two visual pigments in a single photoreceptor cell: identification and histological localization of three mRNAs encoding visual pigment opsins in the retina of the butterfly Papilio xuthus." Journal of Experimental Biology 201, no. 9 (May 1, 1998): 1255–61. http://dx.doi.org/10.1242/jeb.201.9.1255.

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This paper describes the localization of newly identified visual pigment opsins in the tiered retina of the Japanese yellow swallowtail Papilio xuthus. We first cloned three cDNAs encoding visual pigment opsins, PxRh1, PxRh2 and PxRh3, and then carried out histological in situ hybridization to localize their mRNAs in the retina. By combining the present data with our previous electrophysiological results, we concluded that both PxRh1 and PxRh2 correspond to visual pigments expressed in photoreceptor cells sensitive in the green wavelength region (green receptors), whereas PxRh3 corresponds to a pigment in red receptors. The in situ hybridization studies showed that some photoreceptor cells express two opsin mRNAs. In the ventral half of the eye, all green receptors in the distal tier were labelled by both PxRh1 and PxRh2 probes. The labelling by the PxRh2 and PxRh3 probes was detected throughout the eye in the proximal tier; in 18 % of ommatidia, the probes labelled the same photoreceptor cell. These results suggest that the possible co-localization of two different visual pigments will broaden the sensitivity spectrum of the photoreceptor cells.
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Gerard, A., M. Egloff, H. Gerard, A. El Harate, M. Domingo, J. L. Gueant, C. D. Dang, and H. Degrelle. "Internalization of human sex steroid-binding protein in the monkey epididymis." Journal of Molecular Endocrinology 5, no. 3 (December 1990): 239–51. http://dx.doi.org/10.1677/jme.0.0050239.

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ABSTRACT Human sex steroid-binding protein (hSBP) has been purified from late-pregnancy serum and labelled either by iodination (125I) or by photoaffinity with [3H]Δ6-testosterone. Using a micromanipulator, each labelled protein was separately injected into the lumen of epididymal tubules isolated from the head epididymis of the cynomolgus monkey (Macaca fascicularis). Tubules were sampled from 3 to 90 min after the injection and processed for electron microscope autoradiography. Localization of the label occurred over the epididymal epithelium whichever tracer was used. The labelling was not randomly distributed over the different cell types constituting the epithelium, since only the 'principal cells' exhibited a silver grain count significantly greater than the background count. In these cells, labelled protein was found over endocytic organelles (coated structures, endosomes, multivesicular bodies and the trans Golgi network) and nuclei (including the nuclear envelope). Quantitative analysis demonstrated the same pattern of cellular and subcellular distribution for each tracer. Pretreatment with excess unlabelled protein significantly reduced the uptake of radioactivity by the principal cells, demonstrating the specificity of this phenomenon. This is the first study to show direct histological evidence for the internalization of hSBP in the primate epididymis, consistent with earlier immunohistochemical or biochemical localization of this protein. It is concluded that head epididymal cells are able to take up labelled hSBP across their apical membrane. The mechanism of internalization seems to involve endocytosis by the principal cells and leads to labelling of the nuclear compartment. This is strikingly similar to the pattern of uptake of rat androgen-binding protein (rABP) by rat epididymal cells previously demonstrated by our group. To what extent the chemical and structural homology between hSBP and rABP can be held responsible for the common cytophysiological behaviour of these sex steroid-binding proteins remains to be determined.
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Singh, Mahendra, Lubna Khan, and Ankita Kamthan. "Immunohistochemical Expression of Ki-67 and p53 in Surface Epithelial Ovarian Tumour." Journal of Evidence Based Medicine and Healthcare 8, no. 18 (May 3, 2021): 1241–45. http://dx.doi.org/10.18410/jebmh/2021/238.

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BACKGROUND Surface epithelial ovarian tumour (SEOT) develops from the outer surface of ovary. It accounts for more than 90 % of all the ovarian tumours. Most of the SEOT are benign. Few SEOT are of low malignant potential or high malignant potential. The purpose of this study was to assess the rate of expression of proliferative marker Ki-67 and staining pattern of p53 in various histological types of SEOT. METHODS It was a randomised type of study carried out in the Department of Pathology, GSVM Medical College, Kanpur, for 2 years. It included 100 random patients with surgically resected specimens of SEOT. Ki-67 immunohistochemistry (IHC) was performed on all malignant cases and few random benign cases; and the percentage of immunopositive cells in each case was expressed as Ki-67 labelling index (Ki-67 LI). p53 expression was interpreted as positive when cells showed diffuse and intense nuclear staining in malignant cases. RESULTS Out of 100 cases, 70 were benign and 30 were malignant. Cases comprised of serous and mucinous histological subtypes. In all malignant cases, Ki-67 expression was found to be positive (Ki-67 LI > 1 %). Highest Ki-67 LI of 52 % was associated with high grade serous cystadenocarcinoma. High grade serous carcinoma (HGSC) had higher p53 positivity. 88.8 % of HGSC were p53 positive. CONCLUSIONS Ki-67 is a cost-effective proliferative marker; therefore, its assessment can be included in routine histopathological report of SEOT for better understanding of the biologic behaviour and aggressiveness of the tumour. p53 expression was more common in HGSC and can help in discriminating between HGSC and lowgrade serous carcinoma (LGSC). KEYWORDS p53, Ki-67, Ovarian Tumour, Serous, Mucinous, SEOT
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HYOH, Y., M. NISHIDA, T. TEGOSHI, M. YAMADA, R. UCHIKAWA, S. MATSUDA, and N. ARIZONO. "Enhancement of apoptosis with loss of cellular adherence in the villus epithelium of the small intestine after infection with the nematode Nippostrongylus brasiliensis in rats." Parasitology 119, no. 2 (August 1999): 199–207. http://dx.doi.org/10.1017/s003118209900462x.

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It has been reported that infection with Nippostrongylus brasiliensis induces villus atrophy with various histological alterations. In N. brasiliensis-infected rats, villus length in the jejunum was reduced significantly at day 10 p.i., when serum levels of rat mast cell protease (RMCP) II had increased significantly. To determine whether the villus atrophy is associated with enhancement of apoptosis, apoptotic nuclei were labelled using the nick end-labelling method. Numbers of labelled cells were markedly increased in the villus epithelium at 7–10 days p.i., while the numbers returned to normal 14 days p.i. when worms were rejected from the intestine and villus length became normal. Examination of the expression of the adhesion molecule E-cadherin showed granular immunoreactivity in the cytoplasm of atrophic villus epithelium with loss of normal localization to epithelial cell borders. In mast cell-deficient Ws/Ws rats, villus length was reduced as significantly as in +/+ counterparts at day 10 p.i. with marked increases in the numbers of apoptotic cells. These results suggested that villus atrophy was closely associated with enhanced apoptosis and loss of adhesion in epithelial cells. Mast cell activation appears not to be involved in these alterations.
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Vanscheidt, W., A. Laubert, H. Laaff, J. M. Weiss, and E. Schöpf. "Immunohistochemical Localization of Factor XIIIa in Chronic Venous Insufficiency." Phlebology: The Journal of Venous Disease 9, no. 1 (March 1994): 41–45. http://dx.doi.org/10.1177/026835559400900112.

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Objective: Factor XIIIa (FXIIIa) of the coagulation cascade (fibrin stabilizing factor) plays a crucial role in wound healing. Its plasma activity is significantly decreased in patients suffering from diseases accompanied with pathologically increased uptake of fibrin. Design: Immunohistochemical localization of FXIIIa and immunofluorescent histological labelling of fibrin in patients' biopsies and in control specimens. Procedure: Twenty-five biopsies were taken from granulation tissue of venous ulcers. Specimens of unimpaired wound healing ( n = 10) served as controls. Concentrations of FXIIIa and fibrin were estimated in all biopsies. Additionally, 10 biopsies from ulcer edges were stained with FXIIIa. Results: The fibrin uptake in ulcer tissue exceeded the amount found in control biopsies. Specimens taken from the ulcer edges contained the greatest amount of FXIIIa in both pericapillary and interstitial regions, followed by the controls. Granulation tissue taken from venous ulcers showed less FXIIIa around capillaries and in the interstitium than specimens of both other groups. Conclusion: Local FXIIIa deficiency in ulcer tissue may contribute to impaired wound healing. Sclerosis found in ulcer edges may be the morphological correlate of the high enzymatic concentrations found in specimens from this area.
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Moreton, Fiona C., Breda Cullen, Christian Delles, Celestine Santosh, Rosario L. Gonzalez, Krishna Dani, and Keith W. Muir. "Vasoreactivity in CADASIL: Comparison to structural MRI and neuropsychology." Journal of Cerebral Blood Flow & Metabolism 38, no. 6 (May 24, 2017): 1085–95. http://dx.doi.org/10.1177/0271678x17710375.

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Impaired cerebrovascular reactivity precedes histological and clinical evidence of CADASIL in animal models. We aimed to more fully characterise peripheral and cerebral vascular function and reactivity in a cohort of adult CADASIL patients, and explore the associations of these with conventional clinical, imaging and neuropsychological measures. A total of 22 adults with CADASIL gave informed consent to participate in an exploratory study of vascular function in CADASIL. Clinical assessment, comprehensive vascular assessment, MRI and neuropsychological testing were conducted. We measured cerebral vasoreactivity with transcranial Doppler and arterial spin labelling MRI with hypercapnia challenge. Number and volume of lacunes, subcortical hyperintensity volume, microbleeds and normalised brain volume were assessed on MRI. Analysis was exploratory and examined the associations between different markers. Cerebrovascular reactivity measured by ASL correlated with peripheral vasoreactivity measured by flow mediated dilatation. Subjects with ≥5 lacunes were older, with higher carotid intima-media thickness and had impaired cerebral and peripheral vasoreactivity. Subjects with depressive symptoms, disability or delayed processing speed also showed a trend to impaired vasoreactivity. Impaired vasoreactivity and vascular dysfunction may play a significant role in the pathophysiology of CADASIL, and vascular assessments may be useful biomarkers of severity in both longitudinal and clinical trials.
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Tucker, Mary J., and David V. Jones. "Effects of cyproterone acetate in C57Bl/10J mice." Human & Experimental Toxicology 15, no. 1 (January 1996): 64–66. http://dx.doi.org/10.1177/096032719601500112.

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Male and female C57BL/10J mice were fed 0 or 800 ppm cyproterone acetate (CPA) in the diet for 13 weeks. 1 Body weight was reduced (P>0.001 at 13 weeks) by approximately 33%. 2 Seminal vesicle weights were reduced (P>0.001) and showed histological atrophy, changes consistent with the anti-androgenic activity of the compound. 3 Liver weights were increased (P>0.001) by +90% of control mean weights; hepatocyte hypertrophy and increased fat and glycogen were seen by light microscopy, and hyperplasia of smooth endoplasmic reticulin by transmission electron microscopy. 4 Assessment of liver mixed function oxidase activity demonstrated induction of cytochrome P450 enzymes, and increased isozyme 2B1/2 in males and 3A1 in both sexes was confirmed by immunohistochemical staining of liver sections. 5 An increase in bromodeoxyuridine (BrdU) labelling index of the liver was seen in females only. 6 This study is the first in a programme of work with CPA designed to investigate the effects of the compound in mice. It demonstrates that the hepatic effects of the compound which have been described in the rat also occur in mice.
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Charhon, Sam A., Pascale Chavassieux, Georges Boivin, May Parisien, Marie-Claire Chapuy, Jules Traeger, and Pierre J. Meunier. "Deferoxamine-induced bone changes in haemodialysis patients: A histomorphometric study." Clinical Science 73, no. 2 (August 1, 1987): 227–34. http://dx.doi.org/10.1042/cs0730227.

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1. The histological effects of deferoxamine therapy were assessed on transiliac bone biopsies taken after double tetracycline labelling from 16 uraemic patients undergoing chronic haemodialysis, all having aluminium deposits in bone. Eight patients had osteomalacia, five had an ‘aplastic’ bone lesion and three a high bone turnover with a marked increase in osteoid volume. 2. Deferoxamine was administered intravenously once a week at doses ranging from 1 to 6 g for a mean duration of 7.6 ± 3.3 (sd) months. 3. Deferoxamine therapy was associated with significant reductions in stainable aluminium deposits, osteoid volume, osteoid surfaces and thickness index of osteoid seams. The osteoblastic osteoid surfaces as well as the bone formation rates also increased significantly. 4. A rise in resorption parameters and in serum parathyroid hormone levels was observed in patients with osteomalacia. The percentage reductions in stainable aluminium and in osteoid volume were correlated with the degree of hyperparathyroidism. 5. These data show that deferoxamine therapy reduces stainable bone aluminium and improves bone mineralization in low turnover osteomalacia and that the presence of hyperparathyroidism is associated with an increased response to deferoxamine therapy.
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Lengerer, Birgit, Marie Bonneel, Mathilde Lefevre, Elise Hennebert, Philippe Leclère, Emmanuel Gosselin, Peter Ladurner, and Patrick Flammang. "The structural and chemical basis of temporary adhesion in the sea star Asterina gibbosa." Beilstein Journal of Nanotechnology 9 (July 30, 2018): 2071–86. http://dx.doi.org/10.3762/bjnano.9.196.

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Background: Marine biological adhesives are a promising source of inspiration for biomedical and industrial applications. Nevertheless, natural adhesives and especially temporary adhesion systems are mostly unexplored. Sea stars are able to repeatedly attach and detach their hydraulic tube feet. This ability is based on a duo-gland system and, upon detachment, the adhesive material stays behind on the substrate as a 'footprint'. In recent years, characterization of sea star temporary adhesion has been focussed on the forcipulatid species Asterias rubens. Results: We investigated the temporary adhesion system in the distantly related valvatid species Asterina gibbosa. The morphology of tube feet was described using histological sections, transmission-, and scanning electron microscopy. Ultrastructural investigations revealed two adhesive gland cell types that both form electron-dense secretory granules with a more lucid outer rim and one de-adhesive gland cell type with homogenous granules. The footprints comprised a meshwork on top of a thin layer. This topography was consistently observed using various methods like scanning electron microscopy, 3D confocal interference microscopy, atomic force microscopy, and light microscopy with crystal violet staining. Additionally, we tested 24 commercially available lectins and two antibodies for their ability to label the adhesive epidermis and footprints. Out of 15 lectins labelling structures in the area of the duo-gland adhesive system, only one also labelled footprints indicating the presence of glycoconjugates with α-linked mannose in the secreted material. Conclusion: Despite the distant relationship between the two sea star species, the morphology of tube feet and topography of footprints in A. gibbosa shared many features with the previously described findings in A. rubens. These similarities might be due to the adaptation to a benthic life on rocky intertidal areas. Lectin- and immuno-labelling indicated similarities but also some differences in adhesive composition between the two species. Further research on the temporary adhesive of A. gibbosa will allow the identification of conserved motifs in sea star adhesion and might facilitate the development of biomimetic, reversible glues.
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Carbone, Antonino, Alessandro Poletti, Riccardo Manconi, Marzia Cozzi, Sandro Sulfaro, and Rachele Volpe. "Enzyme and Immunohistochemistry of Follicular Hyperplasia in AIDS-related Lymphadenopathy." International Journal of Biological Markers 2, no. 2 (May 1987): 87–94. http://dx.doi.org/10.1177/172460088700200206.

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We used a panel of monoclonal and polyclonal antibodies to analyze frozen and paraffin-embedded lymph node biopsy specimens from 25 intravenous drug abusers (IVDA) with acquired immunodeficiency syndrome (AIDS)-related lymphadenopathy histologically characterized by follicular hyperplasia. Our aim was to obtain diagnostic clues to this commonly occurring pattern. Double-labelling immunohistological studies were also performed on selected frozen sections and 13 plastic-embedded specimens were tested by a number of enzyme reactions. Consistent features in IVDA included abnormally high numbers of intrafollicular T-cells, positive for acid phosphatase and beta-glucuronidase, most of which had Leu-2a-positive phenotype; a marked reduction or loss of mantle zone B-cells (positive for surface IgD-IgM and alkaline phosphatase); and disarray of the network of follicular dendritic reticulum cells (DRCs), as revealed with DRC-1 and anti-S-100 protein antibodies or with reaction for 5'-nucleotidase. When present, distinctive intrafollicular clusters of Leu-2a-positive T-cells and mantle zone B-cells were nearly always associated with areas lacking DRCs in some patients. The intrafollicular hypervascularity invariably found in IVDA proved to be of a true capillary nature, as demonstrated by alkaline phosphatase, 5'-nucleotidase, and ATPase reactions. In control tissues, all showing absence of Leu-2a-positive intrafollicular T-cells, most of the above individual changes could be detected, although they were occasional, mild, and never associated within the same follicle. By contrast, combined immunohistological and enzyme histochemical findings in IVDA indicated that in most follicles such changes were marked and very often associated within the same follicle in each case. It can be concluded that on the basis of a combined analysis of lymphoid and non-lymphoid follicular constituents, the histological changes of AIDS-related lymphadenopathy with follicular hyperplastic pattern are further defined and corroborated.
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Grzanka, Alina, Renata Sujkowska, Alina Janiak, and Miros Adamska. "Immunogold labelling of PCNA and Ki-67 antigen at the ultrastructural level in laryngeal squamous cell carcinoma and its correlation with lymph node metastasis and histological grade." Acta Histochemica 102, no. 2 (January 2000): 139–49. http://dx.doi.org/10.1078/s0065-1281(04)70023-9.

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De Melo, McGinlay, Markus, Macri-Pellizzeri, Symonds, Ahmed, and Sottile. "Live Simultaneous Monitoring of Mineral Deposition and Lipid Accumulation in Differentiating Stem Cells." Biomimetics 4, no. 3 (July 10, 2019): 48. http://dx.doi.org/10.3390/biomimetics4030048.

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Mesenchymal stem cells (MSCs) are progenitors for bone-forming osteoblasts and lipid-storing adipocytes, two major lineages co-existing in bone marrow. When isolated in vitro, these stem cells recapitulate osteoblast or adipocyte formation if treated with specialised media, modelling how these lineages interact in vivo. Osteogenic differentiation is characterised by mineral deposits accumulating in the extracellular matrix, typically assessed using histological techniques. Adipogenesis occurs with accumulation of intracellular lipids that can be routinely visualised by Oil Red O staining. In both cases, staining requires cell fixation and is thus limited to end-point assessments. Here, a vital staining approach was developed to simultaneously detect mineral deposits and lipid droplets in differentiating cultures. Stem cells induced to differentiate produced mixed cultures containing adipocytes and bone-like nodules, and after two weeks live cultures were incubated with tetracycline hydrochloride and Bodipy to label mineral- and lipid-containing structures, respectively. Fluorescence microscopy showed the simultaneous visualisation of mineralised areas and lipid-filled adipocytes in live cultures. Combined with the nuclear stain Hoechst 33258, this approach further enabled live confocal imaging of adipogenic cells interspersed within the mineralised matrix. This multiplex labelling was repeated at subsequent time-points, demonstrating the potential of this new approach for the real-time high-precision imaging of live stem cells.
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Jang, Hoon, Su Jin Kim, Seung Mo Yuk, Dong Seok Han, U. Syn Ha, Sung Hoo Hong, Ji Yeol Lee, Tae Kon Hwang, Seong Yeon Hwang, and Sae Woong Kim. "Effects of anthocyanin extracted from black soybean seed coat on spermatogenesis in a rat varicocele-induced model." Reproduction, Fertility and Development 24, no. 5 (2012): 649. http://dx.doi.org/10.1071/rd11174.

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Varicocele is the most common cause of primary male infertility and is associated with oxidative stress. The aim of the present study was to investigate the effects of anthocyanin on a rat model of varicocele. Twenty-four male rats were divided into four experimental groups: a normal control group, a varicocele-induced control group and two varicocele-induced groups treated with either 40 or 80 mg kg–1, p.o., anthocyanin for 4 weeks. Varicocele was induced by the partial obstruction of the left renal vein. After 8 weeks, the testes and epididymides from rats in all groups were removed, weighed and subjected to histological examination and semen analysis. Apoptosis in the testes was determined by terminal deoxyribonucleotidyl transferase-mediated dUTP–digoxigenin nick end-labelling (TUNEL) and oxidative stress was assessed by measuring 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. Although no significant differences in sperm counts were observed among the groups, anthocyanin treatment of the varicocele-induced groups resulted in significantly increased testes weight, sperm motility and spermatogenic cell density (P < 0.05). Anthocyanin treatment also significantly decreased apoptotic body count and 8-OHdG concentrations (P < 0.05). We suggest that the antioxidant effect of anthocyanin prevented the damage caused by varicocele-induced reactive oxygen species.
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46

Benéton, M. N. C., A. J. P. Yates, S. Rogers, E. V. McCloskey, and J. A. Kanis. "Stanozolol stimulates remodelling of trabecular bone and net formation of bone at the endocortical surface." Clinical Science 81, s25 (October 1, 1991): 543–49. http://dx.doi.org/10.1042/cs0810543.

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1. We studied the mechanism of action of the anabolic steroid, stanozolol, in 23 patients with osteoporosis, using a combination of biochemical and histomorphometric techniques. 2. Treatment with stanozolol (5 mg/day) for 1 year was associated with a marked and significant decrease in the fasting urinary excretion of calcium (P < 0.01) but not with changes in the serum concentrations of calcium and phosphate, the serum activity of alkaline phosphatase, the renal tubular reabsorption of calcium or the urinary excretion of hydroxyproline. 3. Histological examination of trabecular bone showed an increase in bone turnover and the bone formation rate increased twofold (P < 0.02). There were no significant changes in bone volume or wall thickness after treatment. Tetracycline labelling was used to discriminate bone structural units completed before and during treatment. Measurements of the wall thickness of those bone structural units formed during treatment showed no significant change. 4. Measurements made on the endocortical surface also showed an increase in bone turnover, but in contrast to trabecular bone, the bone structural units formed at endocortical sites during treatment had a significantly greater wall thickness than those formed before treatment (P < 0.05). 5. We conclude that stanozolol increases the turnover of trabecular bone and increases the endocortical apposition of bone.
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Mousavinejad, M., S. Skidmore, F. G. Barone, P. Tyers, V. Pisupati, H. Poptani, A. Plagge, et al. "Assessing Human Embryonic Stem Cell-Derived Dopaminergic Neuron Progenitor Transplants Using Non-invasive Imaging Techniques." Molecular Imaging and Biology 22, no. 5 (May 6, 2020): 1244–54. http://dx.doi.org/10.1007/s11307-020-01499-4.

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Abstract Purpose Human pluripotent stem cell (hPSC)-derived dopaminergic neuron progenitor cells (DAPCs) are a potential therapy for Parkinson’s disease (PD). However, their intracranial administration raises safety concerns including uncontrolled proliferation, migration and inflammation. Here, we apply a bimodal imaging approach to investigate the fate of DAPC transplants in the rat striatum. Procedures DAPCs co-expressing luciferase and ZsGreen or labelled with micron-sized particles of iron oxide (MPIOs) were transplanted in the striatum of RNU rats (n = 6 per group). DAPCs were tracked in vivo using bioluminescence and magnetic resonance (MR) imaging modalities. Results Transgene silencing in differentiating DAPCs accompanied with signal attenuation due to animal growth rendered the bioluminescence undetectable by week 2 post intrastriatal transplantation. However, MR imaging of MPIO-labelled DAPCs showed that transplanted cells remained at the site of injection for over 120 days. Post-mortem histological analysis of DAPC transplants demonstrated that labelling with either luciferase/ZsGreen or MPIOs did not affect the ability of cells to differentiate into mature dopaminergic neurons. Importantly, labelled cells did not elicit increased glial reactivity compared to non-labelled cells. Conclusions In summary, our findings support the transplantation of hPSC-derived DAPCs as a safe treatment for PD.
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Ishizuka, Yumiko, Yoshiya Horimoto, Naotake Yanagisawa, Atsushi Arakawa, Katsuya Nakai, and Mitsue Saito. "Clinicopathological Examination of Metaplastic Spindle Cell Carcinoma of the Breast: Case Series." Breast Cancer: Basic and Clinical Research 15 (January 2021): 117822342110394. http://dx.doi.org/10.1177/11782234211039433.

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Background: Spindle cell carcinoma (SpCC) of the breast is a rare histological type, a subtype of metaplastic carcinoma characterized by atypical spindle cell and epithelial carcinoma. The proportions of the spindle cell and epithelial components vary among tumours. Due to its rarity, biological characteristics of this disease have been poorly studied. Methods: In total, 10 patients with SpCC were surgically treated at our institution from January 2007 to December 2018. We retrospectively investigated these SpCC cases, focusing on the differences between spindle cell and epithelial components. Microsatellite status was also examined. Results: Nine cases were triple-negative breast cancer (TNBC). The rates of high tumour grade were 70% in spindle cell components and 56% in epithelial components ( P = .65), while the mean Ki67 labelling index were 63% and 58%, respectively ( P = .71). Mean programmed death ligand 1 (PD-L1) expression in these components was 11% and 1%, respectively ( P = .20). All 10 tumours were microsatellite stable. Patient outcomes of triple-negative SpCC did not differ from those of propensity-matched patients with conventional TNBC. Conclusions: Spindle cell components showed higher values in factors examined, although there was no statistically significant difference. Our data reveal that these 2 components of SpCC may be of different biological nature.
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Patel, Chantal, Elizabeth Jones, Amir Ismail, and Vivek Mudaliar. "An Insight into The Variation of Marker Suture Placement and Labelling For Excisional Biopsies and Different Interpretations of Histological Reports By Plastic Surgeons and Pathologists in the UK." European Journal of Surgical Oncology 45, no. 11 (November 2019): 2200. http://dx.doi.org/10.1016/j.ejso.2019.09.023.

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Chuai, Yunhai, Fu Gao, Bailong Li, Luqian Zhao, Liren Qian, Fei Cao, Lei Wang, Xuejun Sun, Jianguo Cui, and Jianming Cai. "Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals." Biochemical Journal 442, no. 1 (January 27, 2012): 49–56. http://dx.doi.org/10.1042/bj20111786.

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Our recent studies suggest that H2 (hydrogen) has a potential as a novel radioprotector without known toxic side effects. The present study was designed to examine the underlying radioprotective mechanism of H2 and its protective role on irradiated germ cells. Produced by the Fenton reaction and radiolysis of H2O, hydroxyl radicals (•OH) were identified as the free radical species that were reduced by H2. We used a H2 microelectrode to dynamically detect H2 concentration in vivo, and found H2 significantly reduced in situ fluorescence intensity of hydroxyphenyl fluorescein; however, as we treated the mice with H2 after irradiation, the decrease is not significant. We found that pre-treatment of H2 to IR (ionizing radiation) significantly suppressed the reaction of •OH and the cellular macromolecules which caused lipid peroxidation, protein carbonyl and oxidatively damaged DNA. The radioprotective effect of H2 on male germ cells was supported by ameliorated apoptotic findings examined by morphological changes and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) in testicular tissue, and by preserved viability of stem spermatogonia examined for testicular histological parameters, daily sperm production and sperm quality; we used WR-2721 [S-2-(3-aminopropylamino)ethyl phosphorothioic acid] as a reference compound. Our results represent the first in vivo evidence in support of a radioprotective role of H2 by neutralizing •OH in irradiated tissue with no side effects.
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