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Biomedical subjects

S Raza

Publications and source records attributed to S Raza.

At least 37 records · Page 2Linked to original sources
PubMed1998

Do prognostic marker studies on core needle biopsy specimens of breast carcinoma accurately reflect the marker status of the tumor?

Core needle biopsies (CNB) are often used for the diagnosis of breast lesions. In some breast cancer patients, e.g., those treated with preoperative chemotherapy, the CNB specimen might be the only pretreatment tissue sample available for studies of prognostic and predictive markers. Our purpose was to evaluate whether marker studies performed on CNB specimens accurately reflect the marker status of the tumor. Immunostaining for five commonly used prognostic and predictive markers was performed on both CNB and subsequent excision specimens from 56 consecutive patients who had a CNB with carcinoma followed by excision of the tumor. None of the patients received radiotherapy or chemotherapy between the CNB and the excision. Paraffin sections of the CNB and excision specimens were immunostained for bcl-2, estrogen receptor (ER), c-erbB-2, and p53. These markers were scored as positive or negative. Microvessel density (MVD) was scored as a continuous variable on sections immunostained for Factor VIII-related antigen by calculating the average number of microvessels in three 224x fields of highest tumor vascularity ("hot spots"). Immunostaining results for bcl-2, ER, c-erbB-2, and p53 on the CNB and the corresponding excision specimens were 100% concordant. Although there was significant correlation between MVD on the CNB specimens and the corresponding excisions (r = 0.507, P = 0.0002), the mean MVD on the CNB and corresponding excision specimens differed by more than 10% in 85.7% of cases, with differences ranging from 4.3 to 233.3%. MVD was higher in the CNB than in the excision specimens in 30 (61.2%) of 49 cases. In conclusion, in all of the cases studied, accurate results for the dichotomously scored markers bcl-2, ER, c-erbB-2, and p53 were obtained on CNB specimens. In contrast, in most cases, MVD, which was scored as a continuous variable, could not be reliably assessed on the CNB specimen.

Biomarkers, Tumor↗
PubMed1997

Definition of the switch surface in the solution structure of Cdc42Hs.

Proteins of the rho subfamily of ras GTPases have been shown to be crucial components of pathways leading to cell growth and the establishment of cell polarity and mobility. Presented here is the solution structure of one such protein, Cdc42Hs, which provides insight into the structural basis for specificity of interactions between this protein and its effector and regulatory proteins. Standard heteronuclear NMR methods were used to assign the protein, and approximately 2100 distance and dihedral angle constraints were used to calculate a set of 20 structures using a combination of distance geometry and simulated annealing refinement. These structures show overall similarity to those of other GTP-binding proteins, with some exceptions. The regions corresponding to switch I and switch II in H-ras are disordered, and no evidence was found for an alpha-helix in switch II. The 13-residue insertion, which is only present in rho-subtype proteins and has been shown to be an important mediator of binding of regulatory and target proteins, forms a compact structure containing a short helix lying adjacent to the beta4-alpha3 loop. The insert forms one edge of a "switch surface" and, unexpectedly, does not change conformation upon activation of the protein by the exchange of GTP analogs for GDP. These studies indicate the insert region forms a stable invariant "footrest" for docking of regulatory and effector proteins.

Amino Acid Sequence↗
PubMed1997

Complement activation by heparin-protamine complexes during cardiopulmonary bypass: effect of C4A null allele.

OBJECTIVES: The first objective was to determine the effect of inherited differences in the classic pathway complement protein C4 on complement activation by heparin-protamine complexes in cardiac surgery. Specifically, we hypothesized that patients with heterozygous C4A null phenotype (A0BB), who have decreased amounts of C4A, may have increased complement activation because of reduced clearance of heparin-protamine complexes. The second objective was to determine whether heparin-protamine-induced complement activation correlated with postoperative pulmonary shunt fractions. METHODS: C4 typing was performed by agarose gel immunofixation and crossed immunoelectrophoresis. Complement activation was measured by radioimmunoassay of C3a and C4a before cardiopulmonary bypass, after bypass, and after protamine infusion. Shunt fractions were calculated from blood gases. RESULTS: Of the 79 patients, 18 expressed heterozygous C4A null allele (A0BB), 16 had heterozygous C4B null allele (AAB0), three had homozygous C4B null alleles (AA00), and the rest expressed both C4A and C4B alleles (AABB). Patients with heterozygous C4A null allele had significantly increased plasma levels of C4a after protamine neutralization of heparin (C4a of 2862 +/- 375 ng/ml; mean +/- standard error of the mean) when compared with patients with normal expression of C4 alleles (AABB) (C4a of 1580 +/- 141 ng/ml) or heterozygous C4B null allele (C4a 1526 +/- 208 ng/ml). Pulmonary shunt fractions obtained after the operation correlated with the classic pathway complement activation by heparin-protamine complexes, but not with alternative pathway complement activation during cardiopulmonary bypass. CONCLUSIONS: Patients with heterozygous C4A null phenotype have increased complement activation by heparin-protamine complexes during cardiac operations, possibly because of their defective clearance. The classic pathway complement activation by heparin-protamine interaction correlates with postoperative pulmonary shunt fractions.

Alleles↗
PubMed1997

Solid breast lesions: evaluation with power Doppler US.

PURPOSE: To evaluate power Doppler ultrasound (US) in detection of vascularity of solid breast lesions and to correlate patterns of vascular distribution with histopathologic findings. MATERIALS AND METHODS: Eighty-six solid breast masses, which were subsequently sampled for biopsy, were studied with gray-scale and power Doppler US. Patterns of vascular distribution were assigned before biopsy. RESULTS: There were 25 cancers, 38 fibroadenomas, and 23 other benign lesions. Seventeen (68%) cancers had penetrating vessels, four had peripheral vessels, and four had no vessels. Power Doppler US depicted no vessels in 21 fibroadenomas, peripheral vessels in 15, and penetrating vessels in two. Other benign lesions included 11 with no detectable vessels, nine with peripheral vessels, two with central vessels, and one with penetrating vessels. By using penetrating vessels to indicate malignancy, sensitivity for power Doppler US was 68%, specificity was 95%, positive predictive value was 85%, and negative predictive value was 88%. Two cancers were found to be malignant with power Doppler US only. CONCLUSION: The pattern of distribution and morphology of blood vessels in solid breast masses seen at power Doppler US is a potentially important feature to be considered along with other sonographic criteria to predict the likelihood of malignancy.

Breast Neoplasms↗
PubMed1996

Crystal structure of a PDZ domain.

PDZ domains (also known as DHR domains or GLGF repeats) are approximately 90-residue repeats found in a number of proteins implicated in ion-channel and receptor clustering, and the linking of receptors to effector enzymes. PDZ domains are protein-recognition modules; some recognize proteins containing the consensus carboxy-terminal tripeptide motif S/TXV with high specificity. Other PDZ domains form homotypic dimers: the PDZ domain of the neuronal enzyme nitric oxide synthase binds to the PDZ domain of PSD-95, an interaction that has been implicated in its synaptic association. Here we report the crystal structure of the third PDZ domain of the human homologue of the Drosophila discs-large tumour-suppressor gene product, DlgA. It consists of a five-stranded antiparallel beta-barrel flanked by three alpha-helices. A groove runs over the surface of the domain, ending in a conserved hydrophobic pocket and a buried arginine; we suggest that this is the binding site for the C-terminal peptide.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Effect of dolastatin 10 on human non-Hodgkin's lymphoma cell lines.

It is crucial to incorporate new and more potent antineoplastic agents in treating non-Hodgkin's lymphoma since standard chemotherapy fails to cause a significant increase in the survival rate. A potential chemotherapeutic agent is dolastatin 10; hence, the objective of our study is to investigate the effect of the antiproliferative agent dolastatin 10 on different grades of non-Hodgkin's lymphoma cell lines. All cell lines exposed to dolastatin 10 initiated an apoptosis process. Alteration of oncogenes and their product may direct the entry of the cells into apoptosis, among these oncogenes are bcl-2 and c-myc. All cell lines tested expressed c-myc and bcl-2 proteins. However, 24 h after exposing the cell lines to 1 ng/ml dolastatin 10, bcl-2 expression was abolished but there was no significant change in c-myc protein expression. The contradictory roles of c-myc in cell proliferation and death require that other gene(s) products regiment the outcomes of c-myc activity on a cell. A possible candidate for such a modifying gene is bcl-2, whose product prolongs cell survival and blocks apoptosis. Given the above, dolastatin 10 induction of cell arrest is the initiating signal to downregulate the antiapoptotic bcl-2 and reactivate the apoptotic pathway. The reductions in bcl-2 may stabilize the c-myc proliferative action and induce apoptosis.

Antineoplastic Agents↗
PubMed1995

Lactobacillus GG promotes recovery from acute nonbloody diarrhea in Pakistan.

A prospective, placebo-controlled, triple blind clinical trial was carried out in Pakistan to determine the effect of Lactobacillus GG on the course of acute diarrhea in hospitalized children. Forty children (mean age, 13 months) were enrolled and after rehydration received either oral Lactobacillus GG (n = 21) or placebo (n = 19) twice daily for 2 days, in addition to the usual diet. The clinical course of diarrhea was followed during the treatment period. Features on admission into the study groups were similar and were characterized by severe diarrhea, malnutrition and inappropriate management before presentation. Response was evident on Day 2 when the frequency of both vomiting and diarrhea was less in the Lactobacillus group. In those who had presented with acute nonbloody diarrhea (n = 32), the percentage of children with persistent watery diarrhea at 48 hours was significantly less in the Lactobacillus group: 31% vs. 75% (P < 0.01). No significant difference was observed by 48 hours in those presenting with bloody diarrhea. The relevance of this finding to the management of diarrhea in the tropics is discussed.

Acute Disease↗
PubMed1988

Effect of RBCs on the activation of human complement by heparin-protamine complexes.

Complement activation on red cells by heparin-protamine complexes was studied by using whole human serum. C3 bound to red cells was measured by radiolabeled monoclonal antibody to C3, and fluid-phase C5a was determined by radioimmunoassay. Heparin and protamine in clinically relevant concentrations caused the binding of C3 to red cell membranes, and the measurement of C3 binding provided a sensitive indicator of complement activation produced by these complexes. Complement activation by these reagents occurred at concentration ratios of protamine and heparin at which protamine neutralized the anticoagulant effect of heparin. Heparin-protamine complexes appeared to bind to red cells and produce complement activation by the classic pathway. C5a generation with heparin-protamine complexes in serum was greatly enhanced in the presence of red cells and increased with increasing red cell concentration. This enhancement of complement activation in the presence of red cells was also seen as measured by depletion of available C3 hemolytic complement units in the fluid phase. Thus red cells seem to play an important role in activation of complement by heparin-protamine complexes.

Complement Activation↗
PubMed1982

Diamminodichloroplatinum combination chemotherapy in non-oat cell carcinoma of the lung.

A comparison is made between four different but similar approaches to the chemotherapy of 250 patients with nonoat cell bronchogenic carcinoma of the lung. Combination chemotherapy, particularly in regimen where platinum is included, provided no significant advantages over single agent chemotherapy. Side effects attributed to platinum tend to distract from any modest therapeutic gains achieved through its use. Responses rates were not significantly increased through use of platinum in the chemotherapy combination reported in this study.

Carcinoma, Bronchogenic↗