-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Areca nut (commonly known as betel nut) chewing has been shown to be associated with metabolic syndrome and cardiovascular disease (CVD). The mechanism by which betel nut ingestion could lead to development of CVD is not precisely known; however, dyslipidemia hyperhomocysteinemia, hypertriglyceridemia and inflammation could be some of the potential risk factors. This study was undertaken to investigate the effects of two dosages of betel nut on homocysteinemia, inflammation and some of the components of metabolic syndrome, such as hypertriglyceridemia, low HDL-cholesterol, obesity and fasting hyperglycemia in a rat model. METHODS: Thirty-six adult female Sprague Dawley rats, aged 10--12 weeks were divided into three equal groups. Group-1 served as the control group (n = 12) and received water, whereas groups 2 and 3 were given water suspension of betel nut orally in two dosages, 30 mg and 60 mg, respectively for a period of 5 weeks. At the end of the fifth week, the animals were weighed and sacrificed, blood was collected and liver, kidney, spleen and stomach were removed for histological examination.Plasma/serum was analyzed for glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, homocysteine, folate, vitamin B12 and N-acetyl-beta-D-glucosaminidase (NAG) -- a marker of inflammation. RESULTS: When the mean concentration values of 3 groups were compared using one way ANOVA followed by Tukey's HSD-test, there was a significant increase in the concentration of total cholesterol (p = 0.04) in the group receiving 30 mg/day betel nut compared to the control group. However, administration of a higher dose of betel nut (60 mg/day) had no significant effect on the serum concentrations of glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, and NAG. Histological examination of spleen revealed a dose-dependent extramedullary hematopoiesis. No other remarkable change in the tissues (liver, kidney and stomach) was observed.Mean serum/plasma levels of folate, vitamin B12 and homocysteine were not found to be significantly different in all the groups. Betel nut ingestion had no effect on the mean body weights of rats. CONCLUSIONS: Low dosage of betel nut is found to be associated with hypercholesterolemia. However, betel nut ingestion is not associated with hyperhomocysteinemia, hypertriglyceridemia, hyperglycemia, inflammation and increase in body weight in a rat model.
BMC Cardiovascular Disorders 10/2012; 12(1):94. · 1.52 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine BRCA1 status in breast carcinoma patients of Pakistani origin.
Observational study.
The Oncology Clinics of the Aga Khan University Hospital, Karachi, between May 2005 and December 2009.
Fifty three breast cancer patients based on clinical and laboratory diagnosis were recruited for this study. Moderate family history was defined as having a close relative (mother, daughter, sister) diagnosed with breast cancer under 45 years. Peripheral blood samples were collected from each patient in a 5 ml tube containing EDTA as anticoagulant. Subsequent to DNA extraction, mutational analysis of BRCA1 exons 2, 5, 6, 16, 20 and 22 was carried out using single strand conformation polymorphism (SSCP) assay while protein truncation test (PTT) was used to examine mutations in exon 11. All BRCA1 sequence variants were confirmed by DNA sequencing.
Twenty-three patients were diagnosed with early onset breast cancer, 30 patients had moderate family history. At the time of diagnosis, the median age of enrolled patients was 39 years (range 24-65 years). Out of 53 patients, analyzed by SSCP assay, mobility shift was detected in exon 6, 16 and 20 of three patients, whereas one patient was tested positive for mutation in exon 11 by PTT assays. All patients with BRCA1 mutations were further confirmed by DNA sequencing analysis. In exon 16 c.4837A > G was confirmed, which is a common polymorphism reported in several populations including Asians. Moreover, mutations in exon 6 (c.271T > G), exon 20 (c.5231 delG) and exon 11 (c.1123 T > G) were reported first time in the Pakistani population.
Several BRCA1 mutations were observed in Pakistani breast cancer patients with moderate family history. Therefore, mutation-based genetic counselling for patients with moderate family history can facilitate management, if one first or second degree relative or early onset disease is apparent.
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 11/2011; 21(11):680-4.
-
[show abstract]
[hide abstract]
ABSTRACT: Association of Helicobacter pylori (H. Pylori) infection with gastric 'Mucosa Associated Lymphoid Tissue' (MALT) lymphomas (MALTomas) is well established. In this study the frequency and characteristics of gastric MALToma over a period of 18 years was evaluated. During this period 24 patients with gastric MALToma were diagnosed; out of them, 13 (54.2%) had active H. Pylori infection. The mean and median age was 49.7 and 53.5 years. The male: female ratio was 17:7. The common presenting complaints were epigastric pain (n=10) and dyspepsia (n=9). Endoscopic findings revealed mild gastric hyperemia (n=16), superficial erosions (n=4) and superficial ulcers (n=4). It was concluded that the prevalence of gastric MALToma was very low in contrast to a high H. pylori gastritis in the Pakistani population.
Journal of the College of Physicians and Surgeons--Pakistan: JCPSP 03/2011; 21(3):171-2. · 0.34 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The gallbladder specimens of patients who underwent cholecystectomy for symptomatic gallstones between 2003 and 2005 were evaluated for the presence of Intestinal Metaplasia. (IM) and its risk factors. IM was positive in 39% of 293 patients tested, and in the comparative analysis of 114 metaplasia positive versus 179 negative patients, a high risk was found in patients who were 60 years or older [adjusted odds ratio (aOR) = 3.0, 95% confidence interval (CI): 1.5, 6.2]. Other factors with aOR greater than 1 were moderate to excessive use of chilies (1.8) and ethnic origin of North India (1.7). Screening method has yet to be devised for early detection of gallbladder cancer by identifying metaplastic lesions early in life. We believe that large geographic variation and lifestyle environmental factors associated with the development of gallbladder metaplasia and cancer mortality are concealed in our study that needs to be further explored.
International journal of surgery (London, England) 01/2011; 9(6):482-5.
-
[show abstract]
[hide abstract]
ABSTRACT: HER2 gene amplification in invasive breast cancer is a robust predictive marker for response to transtuzumab therapy. This study was undertaken to measure concordance between immunohistochemistry (IHC) and FISH for HER2 gene amplification in invasive breast tumors, as well as the presence of polysomy 17 and possible correlation with demographics and histopathological variables, including ER and PR positivity. A total of 425 cases of infiltrating carcinoma of breast (99% IDC-NOS) were studied. HER2 over expression was tested by IHC and FISH methods. Association between IHC and FISH in both subsets was calculated by amplification ratio including polysomy 17. Out of 425 specimens, 128 (30%) were positive for HER2 amplification by FISH test, whereas only 78 (24%) tumors with 2+ expression showed amplification. In contrast, 39 (74%) demonstrated 3+ IHC score and HER2 gene amplification. The histological variables including tumor size, tumor type, and lymph node involvement did not influence the outcome of FISH analysis. The ER and PR status showed significantly greater positivity in patients negative for HER2 amplification. Polysomy 17 was detected in 23.7% patients and was positively associated with ER and PR expression (P= <0.05). Our study showed a concordance of 24% between 2+ IHC and FISH amplification, while in 3+ IHC cases the concordance was 74%. Significant links of HER2 amplification was seen with ER andPR negativity and higher tumor grade. In addition, non-significant correlations were noted with other variables like tumor type, size and lymph node status.
Asian Pacific journal of cancer prevention: APJCP 01/2011; 12(11):3069-73. · 0.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To study the prevalence and immunohistochemical profile of the subtypes of anaplastic large cell lymphomas (ALCLs) at a major referral center of Pakistan.
Epidemiological data for all mature T-cell non-Hodgkin's lymphoma (NHL) diagnosed between 1st January 2005 and 30th June 2010 at the Aga Khan University Department of Histopathology were reviewed and analyzed with SPSS v17.0.
A total of 178 specimens were diagnosed as mature T- and NK- cell NHL during the period. Of these 100 (56.2%) were diagnosed as systemic ALCL. These tumors were of either T- or null-cell type with consistent (100%) expression of CD30 (Ki-1). Forty three (43%) cases were further classified as ALK positive, fifty (50%) as ALK negative and seven (7%) were not tested for ALK expression. The mean age of the ALK positive group was 26.7 years as compared to the ALK negative of 35.6 years. The gender ratio of ALK positive cases was 2.3:1 (M:F) as compared to the 2.5:1 ratio seen in the ALK negative cases. There were no significant differences in the nodal and extra-nodal involvement patterns between ALK+ and ALK- groups but epithelial membrane antigen was positive more often in the ALK positive group.
Compared to other published studies, this proportion of ALCL within the mature T- and NK- cell lymphoma category was found to be alarmingly high and calls for attention. Further studies should be conducted in our region, which in turn would enable clinicians to successfully battle against this neoplastic disease.
Asian Pacific journal of cancer prevention: APJCP 01/2011; 12(3):685-9. · 0.66 Impact Factor
-
Zubair Ahmad,
Huma Arshad,
Sheema H Hasan,
Saira Fatima,
Romana Idrees,
Kanwal Aftab,
M Abrar Barakzai,
Arsalan Ahmed,
Rashida Ahmed, Shahid Pervez,
Naila Kayani
[show abstract]
[hide abstract]
ABSTRACT: The Section of Histopathology, Aga Khan University is the largest center for histopathology in Pakistan and is the major reporting and referral center for CNS neoplasms in the country. Over the years, a significant increase has been noted in the number of CNS neoplasms reported annually. This increase most likely represents increased number of neurosurgical procedures being performed. A major problem that we face as histopathologists is absence of clinical history or radiological films in a large number of cases.
Asian Pacific journal of cancer prevention: APJCP 01/2011; 12(1):317-21. · 0.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study describes the frequency, demographics, clinical presentation, endoscopic findings, histopathological features, treatment and outcome of 'Immunoproliferative small intestinal disease' (IPSID). Archives contained a total of 27 cases of IPSID diagnosed and treated over an 18-year period. A M: F ratio of 2.4:1 was seen with a mean and median ages of 28.7 and 25 years. Most patients (68.8%) presented with abdominal pain and diarrhoea. In the majority (62.5%), duodenum was the primary site of involvement. Endoscopy showed polypoidal, raised or flat lesions. Biopsy findings included blunting or flattening of villi with dense plasma cell infiltrate and lymphoepithelial lesions. Twenty-four cases were categorized as stage A and B (benign and intermediate) and three were categorized as stage C (malignant, diffuse large B-cell lymphoma with plasmacytoid features). Stage A and B patients responded well to antibiotic treatment (tetracycline) with regression of the lesions while for stage C patients standard CHOP chemotherapy was administered.
Journal of the College of Physicians and Surgeons--Pakistan: JCPSP 01/2011; 21(1):57-8. · 0.34 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We report the case of an 11-year-old girl with squamous cell carcinoma of the tongue. This is a very rare disease in children with only a few cases reported in the literature. There is a great need to create awareness of the harmful and potentially lethal effects of chewing paan and betel nut not only in adults but also in children. Pediatricians and family physicians should also be aware of the possibility of this disease entity occurring at an earlier age so as to decrease delay in diagnosis and initiation of treatment.
Journal of Pediatric Hematology/Oncology 07/2010; 32(5):e199-201. · 1.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Fascin is an actin cross-linking protein, which is part of the cytoskeleton and involved in cell motility in several cell types. The differentiation of epithelial cells is greatly influenced by cell-matrix and cell-cell interactions, which play an important role in the normal organisation and stabilisation of epithelial cells and maintain the cells in a non-migratory state. The malignant conversion of epithelial cells results from a phenotypic switch to a migratory state, which allows tumour invasion beyond the basement membrane, as well as metastasis. Such a switch requires complex rearrangements of the actin cytoskeleton and is governed by multiple actin-binding proteins including fascin. In non-neoplastic lymphoid tissue, fascin expression is highly selective and is predominantly localised in dendritic cells, while lymphocytes, plasma cells, etc are uniformly non-reactive. However, all or nearly all Reed-Sternberg cells and their variants in all types of Hodgkin's lymphoma express fascin and are strongly immunoreactive for fascin. CONCLUSION: Lymphomas (Hodgkin's and non-Hodgkin's) are among the commonest malignancies seen in our practice. The Section of Histopathology at the Aga Khan University, Karachi is the largest centre for histopathology in Pakistan, a densely populated country with an estimated population of 170 million. The authors wanted to test the utility of Fascin in distinguishing between Hodgkin's lymphoma and morphologically closely related forms of non-Hodgkin's lymphoma such as diffuse large B cell non-Hodgkin's lymphoma and anaplastic large cell lymphoma in difficult cases. If found useful, this antibody could help us in reaching a correct diagnosis in difficult cases and allow appropriate patient management.
Journal of clinical pathology 07/2010; 63(7):571-4. · 2.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the effects of lead and zinc on testes.
Randomized control trial. Place and DURATION OF STUDY: Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi, from August 2003 to December 2005.
Sixty adult (90 days old) albino rats were obtained from animal house JPMC for the study and divided into 3 groups. Group A received injection normal saline 1 cc intraperitoneally daily for 8 weeks. Group B received lead chloride in a dose of 10 mg/kg body weight intraperitoneally daily. Group C received zinc chloride in a dose of 1 mg/kg body weight before half an hour of injection of lead chloride in a dose of 10 mg/kg body weight intraperitoneally daily so that to provide pre-treatment. On the day of completion of treatment the animals were sacrificed testes removed and fixed in Bouin's fluid. Testes were dehydrated in the ascending strength of alcohol, 5 mum thick sections were cut and stained with PAS Iron Hematoxylin. Student's t-test was used for statistical analysis with significance at p < 0.05.
The mean diameter of seminiferous tubule was 291.91 + or - 1.18, 198.53 + or - 1.67 and 288.77 + or - 1.11 microm in groups A, B and C respectively. Diameter of seminiferous tubules decreased by 31.99% in group B (p < 0.001; CI 89.023 to 97.736) as compared group A and while group B comparing with group C, the diameter of seminiferous tubules was decreased by 31.25% (p-value = 0.076; CI -94.264 to -86.203). Mean thickness of germinal epithelium was 96.19 + or - 1.01, 50.69 + or - 1.20 and 94.94 + or - 0.54 microm in groups A, B and C respectively. Thickness of germinal epithelium decreased by 47.30 in group B (P < 0.001; CI 42.503 to 48.496) as compared to group A and while comparing group B with group C, the thickness of germinal epithelium was decreased by 46.61% (p=-44.25; CI -46.704 to -41.787).
Zinc prevented toxic effects of lead on germinal epithelium in the albino rats.
Journal of the College of Physicians and Surgeons--Pakistan: JCPSP 06/2010; 20(6):377-81. · 0.34 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the scoring of Estrogen Receptor (ER) status in carcinoma breast by Allred method that is essentially bimodal and to compare the results with a conventional scoring system.
A retrospective, comparative study carried out at Aga Khan University Hospital Section of Histopathology over a period of 18 months, i.e., Jan 2005 to June 2006. Anti ER antibody (clone D07) was used for all IHC stains using envision detection system. ER stains of 860 consecutive breast cancer cases were reviewed and rescored by both conventional and Allred method of ER scoring.
Comparison of results showed that there was a substantial decrease in weak positive cases from 18% to 5% by rescoring using Allred scoring system compared to conventional scoring. The data was analyzed using chi square test.
The sensitivity and specificity of Allred method were calculated; Sensitivity of Allred method was 99.4% & Specificity of Allred method was 99.5% whereas sensitivity and specificity of conventional method was 88.0% and 84% respectively
Journal of the Pakistan Medical Association 05/2010; 60(5):350-3.
-
[show abstract]
[hide abstract]
ABSTRACT: Primary Mediastinal (Thymic) Large B-cell Lymphoma (PMLBL) frequently demonstrates clinical, morphologic and/or immunohistochemical (IHC) features that overlap with mediastinal-classical Hodgkin lymphoma (cHL). Our study compared the immunohistochemical profile of PMLBL versus mediastinal cHL in a cohort of 18 patients, 11 of whom were diagnosed as having PMLBL, and 7 were diagnosed as having mediastinal cHL. Biopsy slides and blocks of all patients were retrieved, and further immunohistochemical workup was done on all the cases. This included staining with a panel of antibodies, including LCA, CD(20), CD(3), CD(30), CD(15), and IRF4/MUM1. All PMLBL cases (100%) showed positivity both for LCA and Pan B (CD(20)), and negativity for Pan T (CD(3)). All mediastinal cHL cases (100%) showed negativity both for LCA and Pan T (CD(3)). Both entities showed variable positivity for IRF4/MUM1, i.e., 73% in PMLBL versus 100% in cHL. CD(30) was expressed in 36% cases of PMLBL versus 100% cases of cHL. CD(15) was expressed in a single case of PMLBL versus 86% cases of cHL. We conclude that 'Leucocyte Cell Antigen' (LCA) is the only marker that was consistently positive in PMLBL and negative in cHL. Other IHC markers, though still helpful, may be expressed in either entity.
Pathology - Research and Practice 02/2010; 206(6):365-7. · 1.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the association of Model for End stage liver disease (MELD) score to the outcome of cirrhotic patients with bacterial infection and to compare it with Child-Turcott-Pugh (CTP) score.
Descriptive study.
The Aga Khan University Hospital, Karachi, from January 2005 to December 2007.
Patients with diagnosis of liver cirrhosis and bacterial infection were included. Demographic features, laboratory data and type of infection were recorded. Multiple logistic regression assays were applied to determine the factors associated with poor outcome in cirrhotics with infection. Receiver-Operating Characteristics (ROC) were used to determine the cut-off values of CTP score and MELD score with the best sensitivity and specificity.
A total of 530 patients, 313 male (59%) with a mean age of 53 +/- 13 years were analyzed. Spontaneous bacterial peritonitis was the predominant infection seen in 369 (69%) patients. One hundred and eighty six (35%) patients died. Factors associated with poor outcome were a CTP score of more than 11 (p=0.001), raised blood urea nitrogen (p=0.020), raised creatinine (p=0.004), shock (p=0.002), and MELD score > 22 (p=0.03). An eight percent increase in mortality rate was noticed with every one point rise in MELD score above 22. ROC curve showed that the specificity of CTP and MELD score to predict poor outcome in these patients was 36% and 59% respectively.
Child-Turcott-Pugh score more than 11, raised BUN and creatinine, shock and high MELD score were poor prognostic markers in cirrhotic patients with infection. MELD score had better specificity than CTP score in determining outcome.
Journal of the College of Physicians and Surgeons--Pakistan: JCPSP 11/2009; 19(11):694-8. · 0.34 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The objective of the study was to determine the incidence and type of endometrial abnormalities in long-term users of tamoxifen with breast cancer. All patients with a diagnosis of Oestrogen Receptor positive breast cancer on Tamoxifen therapy who had also undergone endometrial biopsy for abnormal bleeding or other symptoms were included. Among the 37 cases that had long-term follow up available, 21(57%) had evidence of endometrial pathology. There were seven cases of simple hyperplasia and thirteen of endometrial polyp. Only one case of endometrial carcinoma was seen. These findings support the association between prolonged tamoxifen therapy and endometrial pathology of possible neoplastic potential. Endometrial pathology is dependent on duration of exposure to Tamoxifen, therefore, close follow up of such patients is recommended.
Journal of the Pakistan Medical Association 05/2009; 59(4):249-50.
-
[show abstract]
[hide abstract]
ABSTRACT: The importance of immuno-histological detection of neuroendocrine differentiation in prostatic adenocarcinoma with respect to disease at presentation and Gleason grade is gaining acceptance. There is limited literature on the relative significance of three commonly used markers of NE differentiation i.e. Chromogranin A (CgA), Neuron specific enolase (NSE) and Synaptophysin (Syn). In the current work we have assessed the correlation of immuno-histological detection of neuroendocrine differentiation in prostatic adenocarcinoma with respect to disease at presentation and Gleason grade and to determine the relative value of various markers.
Consecutive samples of malignant prostatic specimens (Transurethral resection of prostate or radical retropubic prostatectomy) from 84 patients between January 1991 and December 1998 were evaluated by immunohistochemical staining (PAP technique) using selected neuroendocrine tumor markers i.e. Chromogranin A (CgA), Neuron specific enolase (NSE), and Synaptophysin (Syn). According to the stage at diagnosis, patients were divided into three groups. Group (i) included patients who had organ confined disease, group (ii) included patients with locally invasive disease, and group (iii) with distant metastasis. NE expression was correlated with Gleason sum and clinical stage at presentation and analyzed using Chi-Square test and one way ANNOVA.
The mean age of the patients was 70 +/- 9.2 years. Group I had 14 patients, group II had 31 patients and group III had 39 patients. CgA was detected in 33 cases, Syn in 8 cases, and NSE in 44 cases. Expression of CgA was seen in 7% of group I, 37% in group II and 35% of group III patients (p 0.059). CgA (p 0.024) and NSE (p 0.006) had a significantly higher expression with worsening Gleason grade.
CgA has a better correlation with disease at presentation than other markers used. Both NSE and CgA had increasing expression with worsening histological grade this correlation has a potential for use as a prognostic indicator. Limitations in the current work included small number and retrospective nature of work. The findings of this work needs validation in a larger cohort.
BMC Urology 01/2009; 8:21. · 1.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Background : This study was conducted to analyze the frequency, expression patterns, and the impact of individual proteins BCL2, BCL6, and p53 on overall survival (OS) in adult, diffuse large B-cell lymphoma (DLBCL) patients. BCL2 gene was further investigated for potential alterations at the DNA level and correlated with OS. Materials and Methods : A total of 117 adult well-characterized DLBCL cases were included. The panel of antibodies comprised CD45, CD20, CD79a, CD3, BCL2, BCL6, and p53. PCR was also employed to correlate the events at the DNA level in BCL2. Results : The mean and median ages were 47.74 and 49 with a M:F ratio of 2.07:1. The incidence of BCL2, BCL6, and p53 expression was observed in 64.10%, 37.60%, and 52.13% of cases, respectively. Amplifiable quality DNA was available from 90 cases. BCL2/IGH translocation was found in 35/90 patients (38.88%) with 24 cases showing BCL2 (MBR)/IGH and 11 cases BCL2 (mcr)/IGH translocation. No association between BCL2 overexpression and BCL2 /IGH translocation was seen. Clinical data were available for 52 patients treated by CHOP therapy. It was found that patients with p53 overexpression had decreased overall survival (P = 0.0004) whereas BCL2, BCL6 expression, and BCL2/IGH translocation had no impact on overall survival. Conclusion : Our data suggest that simple p53 protein expression by IHC at the time of diagnosis may help to identify high-risk patients, who may benefit with more aggressive and newer treatments in addition to standard CHOP.
Journal of Cancer Research and Therapeutics. 01/2009;
-
[show abstract]
[hide abstract]
ABSTRACT: A disrupted cell cycle progression of hepatocytes was reported in chronic hepatitis C virus (HCV) infection, which can contribute significantly in the associated pathogenesis. The present study aimed to further elaborate these disruptions by evaluating the expression of key cell cycle and apoptotic proteins in chronic HCV infection with particular reference to genotype 3. Archival liver biopsy specimens of chronic HCV-infection (n = 46) and normal histology (n = 5) were analyzed by immunohistochemistry using antibodies against proliferation marker Mcm-2, G1 phase marker Cyclin D1, S phase marker Cyclin A, cell cycle regulators p21 (CDK inhibitor) and p53 (tumor suppressor protein), apoptotic protein Caspase-3 and anti-apoptotic protein Bcl-2.
Elevated Mcm-2 expression was observed in hepatocytes in chronic HCV infection, indicating increased cell cycle entry. Cyclin D1 expression was higher than cyclin A, which suggests a slow progression through the G1 phase. Expression of cell cycle regulators p21 and p53 was elevated, with no concordance between their expressions. The Mcm-2 and p21 expressions were associated with the fibrosis stage (p = 0.0001 and 0.001 respectively) and that of p53 with the inflammation grade (p = 0.051). Apoptotic marker, Caspase-3, was mostly confined to sinusoidal lining cells with little expression in hepatocytes. Anti-apoptotic protein, Bcl-2, was negligible in hepatocytes and detected principally in infiltrating lymphocytes. Expression of all these proteins was unrelated to the HCV genotype and were detected only rarely in the hepatocytes of normal liver.
The results showed an arrested cell cycle state in the hepatocytes of chronic HCV infection, regardless of any association with genotype 3. Cell cycle arrest is characterized by an increased expression of p21, in relation to fibrosis, and of p53 in relation to inflammation. Furthermore, expression of p21 was independent of the p53 expression and coincided with the reduced expression of apoptotic protein Caspase-3 in hepatocytes. The altered expression of these cell cycle proteins in hepatocytes is suggestive of an impaired cell cycle progression that could limit the regenerative response of the liver to ongoing injury, leading to the progression of disease.
BMC Microbiology 02/2008; 8:133. · 3.04 Impact Factor
-
European Journal of Pediatrics 02/2008; 167(1):127-8. · 1.88 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hepatic angiosarcomas are rare tumours with poor prognosis, with patients usually dying within 6 months. Metastases mainly occur in lymph nodes, spleen, lungs, bones and adrenals. Metastasis to small intestine is even rarer. Similarly, primary or metastatic angiosarcomas in small intestine are extremely rare, often present with recurrent gastrointestinal bleeding and anemia, and have an extremely poor prognosis. Both primary or metastatic intestinal angiosarcomas may exhibit epithelioid morphology. It may be very difficult to differentiate between primary and secondary cases in intestine and especially when the tumour exhibits epithelioid morphology.
Journal of the College of Physicians and Surgeons--Pakistan: JCPSP 02/2008; 18(1):50-2. · 0.34 Impact Factor
