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Biomedical subjects

S Pervez

Publications and source records attributed to S Pervez.

67 records · Page 4Linked to original sources
PubMed1993

Intraoperative frozen section consultation: an analysis of accuracy in a teaching hospital.

This is a retrospective quality assurance study of all frozen sections done at The Aga Khan University Hospital during a six year period (1986 to 1991). There were 1,031 frozen sections out of a cumulative total of 42,985 surgical specimens (2.39%). Nine hundred and severity-six (94.66%) were concordant. In 92 (8.9%) fresh specimens were brought from other hospitals of Karachi, in 37 cases (3.58%) the diagnosis was deferred till the evaluation of permanent paraffin sections and 18 (1.74%) were discordant with 7 (0.67%) false positive and 11 (1.06%) false negative. Among the discordant cases, 9 were attributed to misinterpretation, 7 due to sampling errors and 2 due to technical reasons. Some of these errors might have been avoided, but appear to be an irreducible minimum.

Frozen Sections↗
PubMed1992

The human squamous cervical carcinoma cell line, HOG-1, is responsive to steroid hormones.

Growth of the human squamous cervical carcinoma cell line, HOG-I, was stimulated in response to oestradiol in serum-containing and chemically defined medium. The oestradiol-stimulated growth could be inhibited by 4-OH tamoxifen, progesterone and medroxyprogesterone acetate; the last 2 compounds also inhibited basal cell growth in serum-containing and chemically defined media. The data are consistent with the sensitivity of human squamous cervical cancer to sex-steroid hormones and suggest that endocrine therapies may be of benefit in this disease.

Adult↗
PubMed1990

Intraperitoneal radio-localization of tumors pre-targeted by biotinylated monoclonal antibodies.

We describe 2-step and 3-step strategies for intraperitoneal tumor radio-localization by means of monoclonal antibodies (MAbs). Nude mice bearing intraperitoneal human colon carcinoma tumors were injected i.p. with biotinylated MAb AUAI, followed 24 hr later by radioiodinated streptavidin (2-step). The uptake of radioactivity in tumor and normal tissues was measured 4 hr after injection of radioactive compound. A 3-step strategy consisted in administering biotinylated antibody, cold avidin after 24 hr and 111In-labelled biotin after a further 4 hr; mice were then killed 2 hr later. Tumor localization of intraperitoneally-administered biotinylated antibody and direct targeting of radioactive streptavidin to biotinylated antibody bound to tumor sites were demonstrated using immunohistochemistry and autoradiography. Our results show that (i) the 2-step approach increased the percentage of radioactivity uptake by tumor with respect to directly labelled antibodies (24% vs. 6%) and improved the tumor/non-tumor ratio; (ii) the 3-step approach allowed faster blood clearance of the radioactive probe (111In-biotin) and yielded high tumor/non-tumor ratios. "Pre-targeting" methods appear to have advantages over the conventional 1-step approach with directly radiolabelled antibody.

Animals↗
PubMed1989

Effect of polarity and differentiation on antibody localization in multicellular tumour spheroid and xenograft models and its potential importance for in vivo immunotargeting.

Two monoclonal antibodies (MAbs) AUAI and HMFGI recognize antigens located on different membrane domains of polarized epithelial cells. We have assessed the accessibility of these antigens in multicellular tumour spheroids produced in culture using a well-polarized (HRA-19) and a non-polarized cell line (LoVo) of human large-bowel carcinoma origin. Multicellular spheroids of HRA-19 cells develop polarity, so that the membrane which is in contact with the culture medium (apical) becomes antigenically distinct from the membrane facing the centre of the spheroids (basolateral). This was confirmed by immunostaining sections of spheroids with 2 MAbs, AUAI and HMFGI. AUAI recognizes an antigen located exclusively on the basolateral membranes of polarized epithelial cells, and stained only internal membranes in spheroid sections. Conversely HMFGI, which recognizes an antigen located on the apical membranes, stained only the periphery of the spheroids. These 2MAbs were then radiolabelled with 125I and incubated with live spheroids for 4 hr at 37 degrees C. Autoradiographs of spheroid sections showed a marked difference between the 2 MAbs. 125I-HMFGI-radioantibody localized exclusively on the spheroid surface in a pattern identical to the in vitro immunostaining pattern, while 125I-AUAI radioantibody showed no binding in spite of the uniform presence of antigen on all tumour cells basolaterally. This appeared to be the result of the inaccessibility of basolateral antigenic sites in well-polarized epithelial cells because of the tight junctions connecting these cells at their apical surfaces. In contrast to the HRA-19 cell line LoVo, spheroids do not develop polarity; as a result, when stained with AUAI, variable antigenic expression all over the cell surface was seen. Autoradiographs of these spheroids showed 125I-AUAI binding with a penetration to a depth of about 1-3 cells, while HMFGI which shows no reactivity with this cell line in vitro, did not bind. This phenomenon was further investigated in xenografts of the HRA-19 cell line. It was shown that in a well-differentiated adenocarcinoma where the tumour cells forming acini are arranged in a polarized fashion, the luminal antigenic sites may be inaccessible to the injected MAb. The striking differences in binding of MAbs on polarized and unpolarized tumours indicate the importance of cell polarization and exact location of antigenic sites for in vivo immunotargeting.

Adenocarcinoma↗
PubMed1989

Kinetics, quantitative analysis and radioimmunolocalization using indium-111-HMFG1 monoclonal antibody in patients with breast cancer.

HMFG1 tumour associated monoclonal antibody IgG1 and F(ab')2 fragments were radiolabelled with indium-111 and used to study patients with breast cancer. In vitro and in vivo stability of the radiolabelled antibodies was shown to be satisfactory. Thirty patients with primary breast cancer underwent tumour resection and quantitative evaluation of the radioactivity in the tumour and normal tissues following administration of specific and non-specific antibodies. The mean tumour uptake of HMFG1 F(ab')2 fragments at 24 h was significantly higher (P less than 0.05) than the intact IgG but at 48 h there was no difference. The mean tumour uptake with the specific antibody was higher than the non-specific antibody of the same subclass (P less than 0.05). Lymph node metastases showed higher antibody uptake than the corresponding primary tumours (P less than 0.05). Fifteen patients with primary or metastatic breast cancer were investigated by external body scintigraphy using HMFG1 F(ab')2 fragments. Successful localisation was observed in approximately 50% of the primary and metastatic lesions with no false positive results. All the patients had observable concentration of 111In in the liver (20% of the injected dose), the kidneys and the spleen. Following i.v. administration, F(ab')2 fragments cleared from the blood more rapidly than the intact IgG. We conclude that HMFG1 F(ab')2 fragments can localise specifically and faster than intact IgG in breast cancer but the sensitivity of the radioimmunoscintigraphy is relatively low. This method needs further improvement before becoming clinically useful for detecting and staging breast cancer.

Adult↗
PubMed1989

Atrial natriuretic peptide levels in plasma and in cardiac tissues after chronic hypoxia in rats.

1. Atrial natriuretic peptide (ANP) levels were measured in cardiac tissues and in plasma from adult rats exposed to chronic alveolar hypoxia for periods of 2 h, 24 h and 7 days. Levels were also measured in rats that were maintained in hypoxia for 7 days and then returned to air for 24 h. 2. Plasma ANP was not altered at 2 h but was significantly increased at both 24 h and at 7 days. Plasma ANP in animals exposed to hypoxia for 7 days was normal 24 h after returning to air breathing, despite the persistence of indices of pulmonary hypertension. 3. No significant right atrial hypertrophy was observed under these conditions of chronic hypoxia. A reduction in right atrial ANP content was found at 24 h and was accompanied by a decrease in the number of electrondense granules per right atrial muscle cell. After exposure to hypoxia for 7 days, right atrial ANP and granule number was not different from control, and no alteration was found in right atrial ANP level after removal from the hypoxic environment. 4. No significant right ventricular hypertrophy was produced by exposure to hypoxia for 2 or 24 h. In the former group ventricular ANP had decreased significantly compared with control. Right ventricular hypertrophy was found in both the hypoxic groups after exposure for 7 days, when selective increases in right ventricular ANP content were found. 5. These findings are consistent with the hypothesis that ANP release occurs on exposure to chronic hypoxia and is independent of the associated cardiac hypertrophy and pulmonary vascular remodelling. The findings may have relevance to the natriuresis and reported changes in the renin-angiotensin-aldosterone axis under hypoxic conditions.

Animals↗
PubMed1989

Invasive aspergillosis: clinical and pathological features of a new animal model.

A new animal model of invasive aspergillosis is described in which female New Zealand White rabbits were immunosuppressed with corticosteroids and cyclophosphamide and were given an intratracheal inoculation of 4 x 10(4) conidia of Aspergillus fumigatus. Thirteen of 15 animals survived during a 10-day-period of observation. Most had clinical signs of a respiratory infection (dyspnoea) and at autopsy there was macroscopic and microscopic evidence of invasive pulmonary aspergillosis. Six control animals (infected but not immunosuppressed) showed no such signs. The extent of hyphal invasion was assessed histologically and quantified by calculating the number of colony forming units (c.f.u.) g-1 of tissue: in the experimental group the mean c.f.u. value for the lungs was 1.25 x 10(3) compared to 73.3 c.f.u. g-1 of lung for the control group (P = 0.003). The infection was also quantified by a whole lung chitin assay: in the experimental group the mean chitin content (expressed as a glucosamine equivalent) was 3.05 micrograms g-1 lung tissue compared to a 0.53 micrograms g-1 lung tissue for the control group (P = 0.01). We conclude that this model of invasive aspergillosis in rabbits reflects closely the pathological features of the disease in man and that it may prove useful for studies of the pathogenesis and the treatment of invasive aspergillosis.

Animals↗
PubMed1988

Localization of monoclonal antibody AUA1 and its F(ab')2 fragments in human tumour xenografts: an autoradiographic and immunohistochemical study.

The mouse monoclonal antibody (MAb) AUA1, when applied on LoVo tumour sections, reacts by staining all tumour cells, on their cell surfaces. To investigate the accessibility of these sites to antibody when the tumour is present as a solid mass in vivo, subcutaneous xenografts of LoVo were first prepared in nude mice. The mice were then injected intravenously with either 125I-labelled AUA1, 125I AUA1 F(ab')2 or with 125I-labelled HMFG2 (negative control antibody). Animals were killed at various time intervals. Gross and micro-autoradiography as well as immunohistochemistry were performed on tissue samples of tumour and control organs. The in vivo injected antibody, in contrast to that studied in vitro, was localized only, as detected by autoradiography, on a thin layer of tumour cells adjacent to the vascularized stroma. On microscopically small tumour islands the antibody penetration was complete. Most of the radioactivity was on the cell surfaces, as seen on in vitro immunostaining. With intact antibody, similar autoradiographic results were obtained at days 1, 3 and 6. With F(ab')2 fragments there was deeper penetration into the tumour at days 1 and 3, though less radioactivity was found; by day 6 the activity had greatly decreased. Radioactivity in the control organs was limited to the blood pool. Negative control antibody HMFG2 showed no localization on the tumour cells. These results were not due to differences in antigenic expression of the tumour cells but reflect the problem of accessibility of antigenic sites in vivo.

Animals↗
PubMed1988

Localization of biotinylated monoclonal antibody in nude mice bearing subcutaneous and intraperitoneal human tumour xenografts.

To demonstrate the precise distribution and binding of in vivo injected monoclonal antibodies on histological tumour sections, we have biotinylated our primary antibody AUA1. Biotinylated antibody was injected into nude mice bearing simultaneous subcutaneous and intraperitoneal xenografts of the human tumour LoVo. Twenty-four hours after injection, the animals were killed, tumours and control organs were removed. Antibody was demonstrated on frozen sections by incubating sections with avidin biotin peroxidase complex. We compared the in vivo penetration and binding of this antibody on intraperitoneal and subcutaneous xenografts. The antibody penetration was mainly restricted to a thin layer of tumour cells adjacent to the vascularized stroma in large solid subcutaneous and intraperitoneal tumours, whereas in very small intraperitoneal tumours, antibody penetration was complete. These findings were similar to our autoradiographic results. This study demonstrates that employing the biotinylated antibodies for in vivo localization studies provides superior resolution of antibody binding for morphological assessment compared to autoradiography. Localization of a biotin label is more precise and will permit ultra-structural studies.

Animals↗
PubMedDate not supplied

Case control study of prognostic markers and disease outcome in inflammatory carcinoma breast: a unique clinical experience.

Inflammatory breast carcinoma (IBC) is a rare but aggressive form of breast cancer. In this first-ever study, we investigated the role of nine prognostic markers' expression (estrogen receptor [ER], progesterone receptor [PR], p53, C-erbB-2, epidermal growth factor receptor [EGFR], cathepsin D [CD], proliferating cell nuclear antigen [PCNA], DNA ploidy, and S-phase fraction [SPF]) and disease outcome in IBC cases compared with the control group. A case control study of IBC was conducted on 40 test cases with two controls per case matching age, grade, and number of axillary lymph nodes sampled. During 7 years of this study, 10% of all patients with breast cancer had IBC. In this study, 84% of IBC cases showed positive axillary lymph nodes compared with 63% in control group. The expression of nine prognostic markers, that is, ER, PR, p53, C-erbB-2, EGFR, CD, PCNA, SPF, and DNA ploidy, was studied by immunohistochemistry and flow cytometry. Hormone receptor status showed an inverse correlation (p < 0.05). Among p53, C-erbB-2, EGFR, and CD in the IBC group, only p53 showed a significant correlation, with 70% positivity in IBC versus 48% positivity in the control group (p < 0.05). Much higher SPF and PCNA positivity was seen in the IBC group compared with the control group (p < 0.05). DNA ploidy also showed a significant correlation compared with the control group (p < 0.05). After a median follow up of 18 months, median overall survival in the IBC group was 1.8 years (range 0.6-5.8 years) compared with 3.0 years (range 2.5-7.0 years), with a p value of 0.0001.

Adenocarcinoma↗
PubMedDate not supplied

Mantle cell lymphoma presenting as solitary polypoid colonic lesions.

Mantle cell lymphoma of the intestine is rare, usually presenting as multiple small polyps. We report three men with colonic mantle cell lymphoma in the form of single large polypoid mass. The clinical picture suggested adenocarcinoma; the diagnosis was made at histology and immunohistochemistry of the colectomy specimens.

Adult↗
PubMedDate not supplied

Flow cytometric and demographic analysis of t cell acute lymphoblastic leukemia in Pakistani population.

BACKGROUND: This study was carried out to analyze the proportion of T cell acute lymphoblastic leukemia (TALL) among all acute lymphoblastic leukemia (ALL) in Pakistani population and its correlation with the demographic features. Accuracy of cell surface markers used in flow cytometric analysis of the leukemic cells was also determined. METHODS: Data of 209 consecutive cases of acute lymphoblastic leukemia (ALL) presenting between July 1995 and July 2003 was analyzed. Flow cytometry was performed on all ALL cases using the standard protocols. TALL markers included CD3, CD5 and CD7. RESULTS: Proportion of TALL among known ALL Pakistani patients was 17.22%. Mean age of the TALL patients was 17.2 years. Proportion of TALL was higher in adults than in children (21.95% vs. 14.17%). Overall in this study there were more male patients affected by TALL (25/36 or 69.40%) than females (11/36 or 30.60%). The female to male ratio among TALL patients was 1:2.27. However, the proportion (%) of TALL in females was higher than males (18.96% vs. 15.82 %) i, e, 1.2:1. CD7 was found to be the most sensitive among both adults & children. It was positive in 94.4% of the TALL cases. CONCLUSION: Proportion of TALL among ALL in Pakistan is similar to that reported in this region, indicating a candidate association with geographical location and socioeconomic status. The reactivity of markers with TALL. cells was similar to what we expected based upon literature. However, due to some aberrant and cross reactivity displayed by each marker, we strongly recommend a panel approach including B and myeloid markers to ensure a correct diagnosis of TALL.

Acute Disease↗