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Biomedical subjects

S Nair

Publications and source records attributed to S Nair.

At least 145 records · Page 8Linked to original sources
PubMed1998

Cloning, expression and characterization of a gene which encodes a topoisomerase I with positive supercoiling activity in pea.

We have isolated and sequenced the full length cDNA for topoisomerase I. Using degenerate primers, based on the conserved amino acid sequences of five eukaryotic topoisomerase I, a 386 bp fragment was PCR amplified using pea cDNA as template. This fragment was used as a probe to screen a pea cDNA library. Two partial cDNA clones were isolated which were truncated at the 5' end. RACE-PCR was employed to isolate the remaining portion of the gene. The total size of the gene was 3055 bp with an open reading frame of 2676 bp. The deduced structure of pea topoisomerase I contain 892 amino acids with a calculated molecular weight of 100 kDa and an estimated pI of 9.3. A comparison of the deduced amino acid sequences of the pea topo I with the other eukaryotic topoisomerases clearly suggested that they are all related. Pea topoisomerase I has been overexpressed in E. coli system and the recombinant topoisomerase purified to homogeneity. The purified protein relaxes both positive and negative supercoiled DNA in the absence of divalent cation Mg2+. In the presence of Mg2+ ions the purified enzyme introduces positive supercoils a unique property not reported in any other organism except in archaebacterial topoisomerase I. Polyclonal antibodies were raised against recombinant topoisomerase I and western blotting with sub-cellular fractions indicated the localization of this topoisomerase in pea nuclei.

Amino Acid Sequence↗
PubMed1998

Purification and characterization of the MUC1 mucin-type glycoprotein, epitectin, from human urine: structures of the major oligosaccharide alditols.

The MUC1 glycoprotein, epitectin, a component of the human bladder epithelium, was purified from human urine. Sedimentation equilibrium analysis and gel filtration using polysaccharide or protein standards revealed a polydisperse preparation with molecular weights ranging from about 0.9 to 1.3 x 10(6). This suggests that in the native state epitectin exists as aggregates of three or four monomer units of 350-400 kDa. Epitectin was found to have significant affinity to hexyl-, octyl- or phenyl agarose indicating that hydrophobic interactions and possibly carbohydrate-carbohydrate interactions may be responsible for the self-association. Chemical and enzymic deglycosylation of [125I]-labeled urine epitectin and metabolically labeled H.Ep.2 epitectin resulted in extremely polydisperse products. The buoyant densities of epitectin purified from urine and H.Ep.2 cells were found to be 1.39-1.40 g ml(-1), suggesting that the total carbohydrate content of these preparations is not significantly different. The O-linked saccharides of epitectin were fractionated by HPLC and analyzed by permethylation and FAB-MS. The neutral saccharides from both sources contain three common structures, namely Gal1 --> 3GalNAc, GlcNAc1 --> 6 (Gal1 --> 3) GalNAc and Gal1 --> 4GlcNAc --> 6 (Gal1 --> 3)GalNAc. The sialic acid of urine epitectin consisted entirely of N-acetylneuraminic acid. The two sources of epitectin, in vitro labeled on sialic acid, were found to have the same sialyl oligosaccharides but in different proportions. Metabolic labeling and N-glycanase susceptibility experiments firmly established the presence of N-linked saccharides in epitectin as minor components. The remarkable similarities in the total carbohydrate content, the carbohydrate composition and structures of saccharides between epitectin from urine, a non-malignant source, and H.Ep.2 cells is surprising in view of the prevailing view that MUC1 glycoproteins of cancer cells are underglycosylated compared to those produced by non-malignant cells.

Amino Acids↗
PubMed1998

Expression of c-erbB3 protein in primary breast carcinomas.

Expression of c-erbB3 protein was investigated in 104 primary breast carcinomas comprising nine comedo ductal carcinoma in situ (DCIS), 91 invasive ductal carcinomas and four invasive lobular carcinomas using two monoclonal antibodies, RTJ1 and RTJ2. Of the 91 invasive ductal carcinomas, seven contained the comedo DCIS component adjacent to the invasive component. An immunohistochemical technique was used to evaluate the association between expression of c-erbB3 and clinical parameters and tumour markers such as epidermal growth factor receptor (EGFR), c-erbB2, cathepsin-D and p53 in archival formalin-fixed paraffin-embedded tumour tissues. Our results indicated that RTJ1 and RTJ2 gave identical staining patterns and concordant results. It was found that the overexpression of c-erbB3 protein was observed in 67% (6/9) of comedo DCIS, 52% (44/84) of invasive ductal carcinomas, 71% (5/7) of carcinomas containing both the in situ and invasive lesions and 25% (1/4) of invasive lobular carcinomas. A significant relationship (P < 0.05) was observed between strong immunoreactivity of c-erbB3 protein and histological grade, EGFR and cathepsin-D, but not with expression of c-erbB2, p53, oestrogen receptor status, lymph node metastases or age of patient. However, we noted that a high percentage of oestrogen receptor-negative tumours (59%), lymph node-positive tumours (63%) and c-erbB2 (63%) were strongly positive for c-erbB3 protein. We have also documented that a high percentage of EGFR (67%), c-erbB2 (67%), p53 (75%) and cathepsin-D-positive DCIS (60%) were strongly positive for c-erbB3. These observations suggest that overexpression of c-erbB3 protein could play an important role in tumour progression from non-invasive to invasive and, also, that it may have the potential to be used as a marker for poor prognosis of breast cancer.

Adult↗
PubMed1998

The ClpC ATPase of Listeria monocytogenes is a general stress protein required for virulence and promoting early bacterial escape from the phagosome of macrophages.

Under stress conditions, the facultative intracellular pathogen Listeria monocytogenes produces a ClpC ATPase, which is a general stress protein encoded by clpC and belonging to the HSP-100/Clp family. A ClpC-deficient mutant was obtained by gene disruption in strain LO28, which became highly susceptible to stress conditions in vitro. Intracellular growth of this mutant was restricted within macrophages, one of the major target cells of L. monocytogenes, during the infectious process. A quantitative electron microscope study showed that, contrary to wild-type bacteria that rapidly gain access to the cytoplasm of macrophages, mutant bacteria remained confined to membrane-bound phagosomes. Only a few mutant bacteria disrupted the phagosome membrane after 4h of incubation, then polymerized actin filaments and multiplied within the cytoplasm. The ClpC ATPase, therefore, promotes early bacterial escape from the phagosome of macrophages, thus enhancing intracellular survival. The ClpC ATPase was produced in vivo during experimental infection by wild-type bacteria. The virulence of the ClpC-deficient mutant was severely attenuated in mice, with a three-log decrease in its 50% lethal dose compared with wild-type bacteria. Bacterial growth of mutant bacteria was strongly restricted in organs, presumably because of an impairment of intracellular survival in host tissues. Our results provide evidence that a general stress protein is required for the virulence of L. monocytogenes, which behaves as a virulence factor promoting intracellular survival of this pathogen.

Adenosine Triphosphatases↗
PubMed1998

Anaplastic ganglioglioma: case report and review of the literature.

A 10-year-old girl underwent radical decompression of a right temporal tumour extending to the insular cortex which proved to be a differentiated ganglioglioma. One year later, she presented with a bleeding right frontal tumour extending to the insula, the histology of which showed it to be the anaplastic variant of ganglioglioma. She underwent postoperative radiotherapy but died 6 months after the second operation. Anaplastic ganglioglioma is a rare variant of ganglioglioma and progression of the latter to anaplastic ganglioglioma is an extremely rare occurrence. The literature regarding ganglioglioma is reviewed.

Brain Neoplasms↗
PubMed1998

Combined levamisole with recombinant interleukin-2 (IL-2) in patients with advanced renal cell carcinoma: a phase II study.

Adoptive immunotherapy (AI) with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells is an antineoplastic modality in which immune-activated cells are administered to a host having cancer in an attempt to mediate tumor regression. Levamisole (LEV), an immune stimulant, has been suggested as having therapeutic effectiveness in a variety of cancers. After a phase I trial of recombinant IL-2 plus LEV, a phase II trial of this combination was conducted in patients who had advanced renal cell carcinoma. The regimen was IL-2 at 3 x 10(6) U/m2 daily x 5 plus LEV at 50 mg/m2 perorally three times a day x 5. Only one of the 22 eligible patients had a regression. It was a partial regression, 85 days in duration. The median time to treatment failure (refusal, progression, or off study because of toxicity) was 36 days. The only grade 4 toxicity reported was lethargy. This regimen is not recommended for further testing in patients who have advanced renal cell carcinoma.

Adjuvants, Immunologic↗
PubMed1998

Phase II trial of topotecan for the treatment of mesothelioma.

The North Central Cancer Treatment Group designed a phase II trial to assess the efficacy and toxicity of topotecan in patients with unresectable malignant pleural mesothelioma. Twenty-two previously untreated patients with unresectable pleural mesothelioma and good performance status (Eastern Cooperative Oncology Group performance status 0, 1, or 2) were enrolled on this trial from October 1993 through July 1994. Nineteen men and three women, median age 66 years (range, 44-78 years), were treated with topotecan 1.5 mg/m2 intravenously over 30 minutes daily for 5 days at 3-week intervals until toxicity, progression of disease, or a patient decided to discontinue treatment. There were seven patients with measurable disease and 15 with evaluable disease; all were assessable for response and toxicity. A total of 113 cycles of treatment were given, for a median of three cycles (range, 1-26 cycles). Myelosuppression was the most frequent toxicity. Eighteen of 21 patients (86%) experienced grade 3 or 4 neutropenia during the initial treatment cycle. The median neutrophil nadir was 0.5 x 10(3)/microl (range, 0.1-1.6 x 10(3)/microl), and the median platelet nadir was 127 x 10(3)/microl (range, 18-460 x 10(3)/microl). Other toxicities more than grade 2 included malaise (two patients), and anorexia, infection, fever, pulmonary, and cardiac in one patient each. There were no objective responses, and 18 patients had stable disease for a median of 74 days. The median survival for all patients was 230 days, with 23% alive at 1 year. Topotecan as administered in this trial is reasonably well tolerated; however, the response rate was insufficient to warrant additional study in pleural mesothelioma.

Adult↗
PubMed1998

Clostridium difficile colitis: factors influencing treatment failure and relapse--a prospective evaluation.

OBJECTIVE: The aim of this study was to identify patient related factors that may influence the treatment response and relapse following Clostridium difficile (C. difficile) colitis. METHODS: A total of 36 patients with C. difficile colitis were followed for 3 months. Age, sex, place of residence, severity of infection, treatment, underlying medical condition, and treatment were compared in patients who failed to respond to treatment in 14 days and in patients who relapsed after a successful treatment. Student's t test and Fisher's exact test were used to compare the groups. A p value of <0.05 was considered significant. RESULTS: A low serum albumin (p=0.016) and continuation of systemic antibiotic treatment were found to be associated with refractoriness to treatment. Continuation or restarting of antibiotics after successful treatment increases the risk of relapse (p=0.003). The age, sex place of residence, underlying medical condition, and type of precipitating antibiotics had no effect on the treatment response and relapse. The severity of colitis and the type of therapy (metronidazole vs vancomycin) did not influence the treatment response or relapse. CONCLUSION: Low serum albumin serves as a useful marker for patients who require prolonged treatment for C. difficile colitis. It is prudent to review the need for the continuation of systemic antibiotic treatment, as it adversely affects the treatment response and increases the risk of relapse.

Aged↗
PubMed1998

Giant true diverticulum of sigmoid colon.

A case of giant true diverticulum of the sigmoid colon, manifesting as pain and abdominal mass is presented. The patient is asymptomatic after resection of the diverticulum and end-to-end anastomosis of the colon.

Aged↗
PubMed1998

An adolescent girl with abnormal liver profile.

A 17-year-old previously healthy high school student who lived in a dormitory was referred to our office by her private physician for evaluation of abnormal liver function tests. She was sexually active with one partner but denied any current or past substance abuse. The patient was not taking any medications or nutritional supplements. Family history was unremarkable. Physical examination revealed scleral icterus and minimal hepatomegaly. Spleen was not palpable. The liver function tests are shown in table 1. Total leucocyte count was 6.3 x 10(9)/1 with 53% lymphocytes. The platelet count was normal. Anti-Hbc IgM antibody was negative, so were anti-HAV IgM and anti-HCV antibodies. HBsAg was negative and anti-HBs antibody was positive. Erythrocyte sedimentation rate was 16 mm in the first hour. An abdominal sonogram was done to evaluate a persistent elevation in alkaline phosphatase and it showed only hepatomegaly.

Adolescent↗
PubMed1998

Factors involved in the diagnosis of oral squamous cell carcinoma in Malaysia.

The delay in the diagnosis of oral cancer has been variously reported as being contributed by the clinicians, patients or both. The purpose of this study was to evaluate the referral pattern of 65 patients eventually diagnosed as having oral squamous cell carcinoma. The results showed that 50% of the patients delayed seeking professional help for more than 3 months after being aware of the lesion. The majority of the patients consulted medical practitioners as the first source of help. The mean clinicians' and patients' delay were 10.3 weeks and 28.9 weeks respectively. Dental practitioners showed a tendency to refer more advanced lesions compared to the medical practitioners. The findings raise the concern that lack of patients' awareness, misdiagnosis by clinicians and late detection by dental practitioners prevail thus calling for urgent measures towards early detection of the disease.

Aged↗
PubMed1998

Fenestration of the proximal anterior cerebral artery (A1) with aneurysm manifesting as subarachnoid hemorrhage--case report.

A 50-year-old female presented with rare fenestration of the proximal anterior cerebral artery (A1 segment). This rare congenital anomaly was associated with an aneurysm at the proximal end of A1 fenestration causing subarachnoid hemorrhage, and aplasia of the contralateral A1 segment. Surgical treatment to clip the aneurysm resolved her symptoms. Hemodynamic stress at the arterial fenestration probably caused the aneurysm, possible induced by aplasia of the contralateral A1 segment.

Aneurysm, Ruptured↗
PubMed1998

Antioxidant phenolics and flavonoids in common Indian foods.

To determine antioxidant phenolics and flavonoids in commonly consumed Indian foods we chemically analysed 85 food-stuffs comprising of cereals, pulses, nuts, oilseeds, vegetables, fruits and beverages. Total phenolics were measured biochemically and flavonoids were measured as a sum of quercetin, kaempferol, luteolin and pelargonidin. High flavonoid content (> 100 mg/100 gm) was present in tea, coffee, apple, guava, terminalia bark, fenugreek seeds, mustard seeds, cinnamon, red chili powder, cloves and turmeric. Medium levels (50-100 mg) were found in Indian gooseberry, omum, cumin, cardamom, betel leaf and brandy. Small but significant amounts were also present in food-items of large consumption such as kidney beans, soyabeans, grapes, ginger, coriander powder, bajra and brinjal.

Antioxidants↗
PubMed1998

Migrants in a maelstrom.

"The first victims of Asia's economic crisis are the millions of migrant workers whose labour is no longer required by the region's erstwhile ¿tigers'. Their repatriation raises serious political, economic and social issues for citizens and states in both home and host countries.... The issue of economic migration needs to be assessed if the possible socio-economic consequences of the present crisis are to be fully understood."

Asia↗