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Biomedical subjects

S Saxena

Publications and source records attributed to S Saxena.

At least 109 records · Page 6Linked to original sources
PubMed1998

Heat shock protein (HSP) expression and proliferation of tubular cells in end stage renal disease with and without haemodialysis.

BACKGROUND: Prolonged dialysis is associated with acquired cystic kidney disease (ACKD) and also higher incidence of renal cell carcinoma. Relationship among dialysis, tubular cell proliferation, development of cystic change and neoplastic transformation is not clearly known. Whether dialysis causes additional stress on tubular cells is also conjectural. Study of heat shock protein (HSP) expression which are rapidly synthesized in cells in response to a variety of stresses may be helpful in this regard. METHODS: To evaluate dialysis induced early changes in end stage renal disease (ESRD), kidneys from eight adult autopsied patients were examined (group I) who were on weekly maintenance haemodialysis for 3-12 months. The heat shock protein (HSP 72/73) expression of tubular epithelial cells and their proliferating cell nuclear antigen (PCNA) labelling index (LI) were studied by immunohistochemistry using monoclonal antibodies. For comparison similar study was carried out in 10 cases of ESRD (Group II) of similar age and sex distribution who were not dialysed. The atrophic tubules were subtyped morphologically into (1) classic, (2) thyroid, (3) endocrine and (4) super tubules. RESULTS: In the dialysed group (I) the percentage of hyperplastic super tubules (10.6 +/- 4.1%) was significantly higher than in the non-dialysed group (II) (5.2 +/- 1.3%) with a higher PCNA LI (6.8 +/- 2.04%) (group II 4.9 +/- 1.9%) (P < 0.01 to < 0.001). Though grossly not detected, but microscopic cysts and microadenoma like areas were seen in all the cases in group I with a mean diameter of 522.66 +/- 315.25 microns and 494.85 +/- 262.46 microns respectively. They were seen in one case of group II. PCNA LI of the cells in microadenoma (7.2 +/- 3.1%) and microcysts (6.6 +/- 2.6%) were similar to that of super tubules in group I. Quantitation of HSP expression by image analysis (optical density 2.309 +/- 0.155) showed a positive correlation (r = 0.7555) (P < 0.001) with PCNA LI in super tubules indicating a higher induction in the dialysed group. CONCLUSIONS: This study suggests that haemodialysis may cause injury to tubular cells and aggravate stress on an already compromised situation of ESRD leading to increased cell proliferation and more hyperplastic supertubule formation which may be the forerunner of cyst formation as well as neoplastic transformation.

Adult↗
PubMed1998

Diagnosis and management of idiopathic macular holes.

Modern vitreoretinal surgery is now one of the most effective tools for treating posterior segment diseases. Recent advances in the pathogenesis and classification and better indicators of visual outcome for idiopathic macular holes have led to a renewed interest in this clinical entity. Refinements in the techniques and instrumentation have led to improvement in surgical results. This article reviews the diagnosis and management of idiopathic macular holes.

Diagnosis, Differential↗
PubMed1998

Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder.

BACKGROUND: Neuroimaging studies provide strong evidence that the pathophysiology of obsessive-compulsive disorder (OCD) involves abnormal functioning along specific frontal-subcortical brain circuits. METHOD: A literature search was carried out for all brain imaging studies of patients with OCD. We also reviewed the basic science literature on the functional neuroanatomy of cortico-basal ganglia circuits, and integrated this information with neuroimaging data in OCD to formulate a theoretical model of brain mediation of OCD symptoms and response to treatment. RESULTS: At least a subgroup of patients with OCD may have abnormal basal ganglia development. Functional neuroimaging studies indicate that OCD symptoms are associated with increased activity in orbitofrontal cortex, caudate nucleus, thalamus and anterior cingulate gyrus. CONCLUSIONS: OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits, perhaps due to an imbalance of tone between direct and indirect striato-pallidal pathways. We present a model which describes how frontal-subcortical brain circuitry may mediate OCD symptomatology, and suggest a hypothesis for how successful treatments may ameliorate symptoms, via their effects on circuit activity.

Brain Diseases↗
PubMed1997

The E1B 19K/Bcl-2-binding protein Nip3 is a dimeric mitochondrial protein that activates apoptosis.

Nip3 (nineteen kD interacting protein-3) is an E1B 19K and Bcl-2 binding protein of unknown function. Nip3 is detected as both a 60- and 30-kD protein in vivo and in vitro and exhibits strong homologous interaction in a yeast two-hybrid system indicating that it can homodimerize. Nip3 is expressed in mitochondria and a mutant (Nip3(163)) lacking the putative transmembrane domain and COOH terminus does not dimerize or localize to mitochondria. Transient transfection of epitope-tagged Nip3 in Rat-1 fibroblasts and MCF-7 breast carcinoma induces apoptosis within 12 h while cells transfected with the Nip3(163) mutant have a normal phenotype, suggesting that mitochondrial localization is necessary for induction of cell death. Nip3 overexpression increases the sensitivity to apoptosis induced by granzyme B and topoisomerase I and II inhibitors. After transfection, both Nip3 and Nip3(163) protein levels decrease steadily over 48 h indicating that the protein is rapidly degraded and this occurs in the absence of cell death. Bcl-2 overexpression initially delays the onset of apoptosis induced by Nip3 but the resistance is completely overcome in longer periods of incubation. Nip3 protein levels are much higher and persist longer in Bcl-2 expressing cells. In conclusion, Nip3 is an apoptosis-inducing dimeric mitochondrial protein that can overcome Bcl-2 suppression.

Adenovirus E1B Proteins↗
PubMed1997

Role for Bcl-xL as an inhibitor of cytosolic cytochrome C accumulation in DNA damage-induced apoptosis.

Cytochrome C is a mitochondrial protein that induces apoptosis when released into the cytosol or when added to cell-free extracts. Here we show that cells that overexpress the Bcl-2-related protein Bcl-xL fail to accumulate cytosolic cytochrome C or undergo apoptosis in response to genotoxic stress. Coimmunoprecipitation studies demonstrate that Bcl-xL associates with cytochrome C. Cytochrome C binds directly and specifically to Bcl-xL and not to the proapoptotic Bcl-xs protein. The results also demonstrate that Bcl-xs blocks binding of cytochrome C to Bcl-xL. Our findings support a role for Bcl-xL in protecting cells from apoptosis by inhibiting the availability of cytochrome C in the cytosol.

Apoptosis↗
PubMed1997

Absorption lineshapes in two-dimensional electron spin resonance and the effects of slow motions in complex fluids.

A methodology for obtaining pure absorption two-dimensional electron spin resonance spectra is presented for the case of large inhomogeneous broadening and/or slow motions. For slow motions, the spectra consist of "complex Lorentzians" superimposed with complex weighting factors, presenting a challenge to obtaining absorption spectra. It is shown how absorption-type spectra can be recovered for the two-pulse COSY and SECSY experiments in such cases. For three-pulse 2D ELDOR experiments, absorption lineshapes can be obtained for the autopeaks, whereas the cross peaks would be of mixed-mode character, in general. However, for practical cases the dispersive components in the cross peaks will be relatively small. Theoretical and experimental absorption spectra are provided to illustrate the method and to show the improved resolution obtained from absorption lineshapes. In particular, the variation in linewidths across a SECSY spectrum, which is a key component in elucidating motional dynamics, is clearly rendered in the pure absorption mode. A convenient method for introducing the necessary phase corrections for the slow-motional spectra is also provided.

Absorption↗
PubMed1997

Increased incidence of glomerulonephritis following spleno-renal shunt surgery in non-cirrhotic portal fibrosis.

In a prospective study of 200 non-cirrhotic portal fibrosis (NCPF) patients, 7% had mild proteinuria and their renal biopsies showed mild mesangial proliferative glomerulonephritis (mes-PGN). The remaining 93% biopsies were normal. However, following the insertion of a spleno-renal shunt (SRS) for portal hypertension 32% of these patients developed nephrotic syndrome in five years. Renal histology revealed mesangiocapillary glomerulonephritis (MCGN) (18.5%), mes-PGN (9%), minimal change nephropathy (3%), and chronic sclerosing GN (1.5%). Immunofluorescence showed granular deposition of IgA and C3. IgA2 was the predominant form of Ig in the glomerular deposits, indicating that IgA in the immune complexes was derived from the gastrointestinal tract. Electron microscopy revealed electron dense deposits in the mesangium. In contrast to the NCPF patients who underwent a SRS for portal hypertension, the 200 patients in our study who underwent spleno-renal shunting because of extra hepatic portal obstruction did not have renal disease, nor did they develop renal disease during the five-year post-operative follow-up. Fifty percent of the glomerulonephritis (GN) in the NCPF group progressed to renal failure in five years; 46.6% continued to have proteinuria. Low serum complement, C3 (40%) and circulating immune complexes (14.8%) were detected in the glomerulonephritis group. Our study shows that: (i) there is a high rate of the occurrence of GN following SRS in NCPF patients, but not in those with normal livers; (ii) the type of GN is primarily IgA nephropathy; and (iii) the GN could be the result of defective hepatic reticuloendothelial function in the NCPF group that is worsened by the shunting procedure.

Adolescent↗
PubMed1997

Specific antibodies to Trypanosoma cruzi among blood donors in Los Angeles, California.

BACKGROUND: Trypanosoma cruzi, the cause of Chagas' disease, is often transmitted by transfusion in Latin America. Previous studies showed that at least 1 in 1000 eligible blood donors at the Los Angeles County+University of Southern California (LAC+USC) Medical Center Blood Bank had specific antibodies to T. cruzi. In June 1993, serologic screening of prospective allogeneic donors at epidemiologic risk for T. cruzi infection was begun voluntarily. STUDY DESIGN AND METHODS: The risk of T. cruzi infection in all eligible donors was assessed by questionnaire. At-risk donors were screened serologically for antibodies to T. cruzi with an enzyme immunoassay, and confirmatory testing was done with a radioimmunoprecipitation assay. RESULTS: During the 29-month study period 1311 (39.5%) of 3320 donors were judged to be at risk for T. cruzi infection. Seven donors (1/475) were reactive by an enzyme immunoassay, and six of these seven (1/ 553) were positive in a radioimmunoprecipitation assay. All radioimmunoprecipitation assay-positive donors had been born in countries in which Chagas' disease is endemic. One person in this group had received a transfusion in his homeland. CONCLUSION: These results demonstrate that a substantive proportion of eligible blood donors at our institution have antibodies specific for T. cruzi and that a commercially available assay can be used to detect these antibodies. Our data suggest that the risk of transmission of T. cruzi by transfusion could be eliminated by serologic testing limited to persons born in or transfused in countries in which Chagas' disease is endemic.

Adult↗
PubMed1997

Mutagenic and genotoxic activities of four pesticides: captan, foltaf, phosphamidon and furadan.

The mutagenic and genotoxic potential of four pesticides viz. captan, foltaf, phosphamidon and furadan was evaluated by the Ames mutagenicity assay and their DNA damaging ability on radiation repair defective E. coli K-12 strains respectively. The mutagenic spectrum revealed captan to be most mutagenic in the absence of metabolic activation, while the presence of S9 mix led to an attenuated mutagenic response. Foltaf, phosphamidon and furadan were detected as relatively weaker mutagens. A significant decrease in the survival of SOS defective mutants, recA, lexA and pol- of E. coli was observed as compared to their wild-type counterparts in the presence of the pesticides. The role of SOS repair genes gains further support from the Salmonella strains triggering the error-prone SOS response.

Captan↗
PubMed1997

Role of steroid hormone and growth factor receptors and proto-oncogenes in the behavior of human mammary epithelial cancer cells in vitro.

The cultivation of cells from primary breast cancers is very unpredictable. The majority of breast-cancer-derived cell lines are of metastatic origin. To define the characteristics of tumor cells which govern their ability to grow in vitro as primary cultures as well as continuous or established culture cell lineages, human mammary epithelial cancer (HMEC) cells from 18 cases of unselected primary breast cancer were propagated in culture. Propagation of HMEC cells in vitro as monolayers in primary culture was successful in 10 out of 18 (55.5%) cases, which showed continous proliferation of tumor cells only up to 6-8 passages before they reached senescence. An investigation of the effects of phenotypic expression of estrogen receptors (ER), the progesterone receptors, c-erbB-2 oncoprotein and epidermal growth factor receptors (EGFR) on the capacity of HMEC cells to grow in vitro as monolayers showed that expression of ER and EGFR is required for controlling tumor proliferative activity in vitro. Expression of ER protein made the growth of HMEC cells more difficult, while expression of EGFR protein made their growth in vitro easier. Phenotypic characteristics of floating HMEC cells were found to be different from those grown on cover slips as adherent cultures, suggesting a selective growth of HMEC cells of a specific phenotype in culture. Cultured HMEC cells in subsequent passages showed a decrease in their proliferative capacity, alterations in phenotypic characteristics and development of morphologic features of terminal differentiation, resulting in senescence.

Biomarkers, Tumor↗
PubMed1997

Treatment of acute rejection in live related renal allograft recipients: a comparison of three different protocols.

We present our experience on the comparison of three different modes of steroid therapy, oral prednisolone (OP), intravenous dexamethasone (IVDX) and intravenous methylprednisolone (IVMP) in the treatment of acute rejection (AR) in renal allograft recipients. Between January 1980 and January 1992, 206 patients underwent live related renal transplantation. Before 1990, all received prednisolone (PRED) and azathioprine (AZA) only. After 1990, patients were given PRED, AZA and cyclosporine (CsA). After 1 year, CsA was stopped and patients were converted to a two-drug regimen only. Of the 206 patients, 180 (87.4%) were male and mean age was 30.3+/-8.7 years (range 14-63). During the mean follow-up of 43.5 months, 178 episodes of AR were seen in 121 patients. Each episode was considered as a separate entrant in the study. Conventional immunosuppression was given in 151 episodes and 27 episodes were on triple-drug therapy. Diagnosis of AR was made by clinical, sonography, nuclear scan with or without graft biopsy evidence. Of the 178 AR, 110 (61.8%) were within 3 months, 36 (20.2%) were between 3 months and 1 year and 32 (18%) were after 1 year. OP was given in 11 cases while IVDX and IVMP were given in 48 and 119 cases respectively. Overall, 154 (86%) showed either a complete or partial response to antirejection therapy. Response to therapy was 91, 90 and 85% in OP, IVDX and IVMP groups respectively. There was no statistical difference in response rate in different groups. There was also no difference in side effects in three different groups. Our data suggest that it is the high dose of steroid rather than mode of therapy which is responsible for therapeutic benefit in treatment of AR.

Acute Disease↗
PubMed1997

Role of interferon-alpha-2b in the prevention of superficial carcinoma of the bladder recurrence.

In order to study the tolerability, toxicity and therapeutic efficacy of interferon-alpha2b (Intron-A), 20 patients with superficial transitional cell carcinoma (TCC) of the urinary bladder (Ta, T1) were given intravesically a low dose (9 million IU) of the drug mixed with 30 ml physiological saline for 8 weeks, starting 1 week after transurethral resection (TUR). Follow-up included urine cytology, ultrasonography of the abdomen and cystourethroscopy. Eleven patients (55%) had no signs of recurrence during a follow-up of 6-32 months (mean duration 24 months). Four patients (20%) had superficial tumor recurrence and 5 patients (25%) showed recurrence with progression to invasive tumors. Tolerability was very good, while toxicity in the form of mild flu-like symptoms was observed in only 3 patients. This pilot study showed that, at a low dose, intravesical interferon therapy can significantly lower the recurrence rate in superficial TCC of the urinary bladder with good tolerance and practically no side effects.

Administration, Intravesical↗
PubMed1997

Diagnosis of glomerular haematuria: role of dysmorphic red cell, G1 cell and bright-field microscopy.

Differentiation between glomerular and non-glomerular haematuria by observation of the changes in red cell morphology using phase-contrast microscopy is a well established technique. However, the method is not widely accepted in clinical practice because of controversy regarding the minimum percentage of dysmorphic red cells required to diagnose glomerular aetiology, as well as the need for specialized microscopes. Recently, a glomerular-specific morphological alteration of red cells has been described, which has the form of a doughnut shape with one or more blebs and which is termed the "G1" cell. In the present double-blind prospective study 250 urine samples were examined without any knowledge of diagnosis. Haematuria was detected in 122 cases. The type of haematuria was characterized by counting dysmorphic cells and G1 cells separately, in each case using a phase-contrast microscope as well as an ordinary bright-field microscope with and without staining of urinary sediments. The results were later correlated with the confirmed diagnosis. The study showed that the G1 cell is more specific than the dysmorphic cell for the diagnosis of glomerular haematuria. Evaluation of both dysmorphic red cells and G1 cells can be done using bright-field microscopy with 100% specificity and sensitivities of 82 and 100%, respectively. It has been concluded that the ordinary bright-field microscope can be used for the diagnosis of glomerular haematuria with an efficiency similar to that of a phase-contrast microscope.

Adolescent↗
PubMed1997

Alcohol, Europe and the developing countries.

Although most of the developing countries currently have a lower overall per capita consumption of alcohol than the European countries, the rapid rate of increase in recent years is highly significant from a public health perspective. Excessive alcohol consumption in developing countries leads to substantial negative effects on the health and also on the quality of life of the drinking individuals and their families. It also causes massive direct and indirect costs to these countries that they can ill-afford. Europe has played a major facilitatory role for alcohol consumption in the developing countries and its continues to have considerable influence directly and indirectly even now. Increased international cooperation on scientific as well as policy issues is likely to achieve the twin aims of limiting alcohol use and preventing alcohol-related health and social problems not only in Europe but all over the world, including in the developing countries. Important initial steps in this direction may be increased exchange of information, developing compatible policies and evolving culturally relevant public health measures. In order to achieve any success in limiting alcohol related problems, the need to keep a global perspective on alcohol is paramount.

Alcohol Drinking↗
PubMed1997

Screening of prostate cancer in males with prostatism.

Comparison of different screening methods including digital rectal examination (DRE) and estimation of serum prostate specific antigen (PSA) had been done for detection of cancer prostate at initial stages in 186 patients presenting with prostatism. The detection rate of raised serum PSA (> 4 ng/dl) was found significantly higher than that of abnormal DRE because it could detect cases of prostate cancer at very early stages. On the other hand using abnormal DRE alone as criteria for biopsy, large number of these cases, specially at early stages, would have remained undetected (36.9%) thereby giving false low incidence. Serum PSA was found raised in pre neoplastic conditions (73.9%) like PIN and AAH also, majority of which were missed on DRE (65.2%). Raised serum PSA was found in many benign conditions (36.7%, false positive) also, hence prostatic biopsy is advised to confirm malignancy.

Aged↗