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Biomedical subjects

U Datta

Publications and source records attributed to U Datta.

At least 19 recordsLinked to original sources

Glomerular basement membrane thickness in normal adults and its application to the diagnosis of thin basement membrane disease: an Indian study.

Microscopic hematuria of non-urologic origin warrants ultrastructural study of renal biopsy. Thinning and variations in the texture of glomerular basement membrane (GBM) are difficult to be recognized under light microscope; transmission electron microscope (TEM) therefore plays a vital role in identifying such changes. Ultrastructural morphometry is a valuable diagnostic aid when GBM is suspected of being abnormally thin. In an effort to determine the normal GBM thickness (GBMT) in Indian adults and to determine the cutoff value of GBMT for a diagnosis of thin basement membrane disease (TBMD), we determined GBM thickness in 25 normal adults. Postmortem biopsies of 25 normal adults (16 males and 9 females) aging between 18-58 years were included in the study. GBM thickness was determined through ultrastructural morphometry on accurately enlarged electron micrographs as harmonic mean of 50 orthogonal intercepts across the GBM in each case. Study revealed a mean GBM thickness of 321 nm with a standard deviation (SD) of 28 nm. Mean-2SD (321-56), that is 265 nm, was fixed as cutoff value of GBMT for the diagnosis of TBMD. A systematic split study of control subjects revealed thicker GBM (329+/-38 nm) in higher age group (35-60 years) as compared to GBMT (316+/-21 nm) in lower age group (18-30 years). Males in higher age group also revealed thicker GBM (males: 343+/-39 nm versus females: 300+/-12 nm). Ten patients with non-urologic hematuria and having GBMT<265 nm were diagnosed as cases of TBMD. Patients with TBMD revealed significantly attenuated GBM as compared to age and sex matched controls (214 +/- 40 nm versus 311 +/- 17 nm; p<0.0005). No overlap was observed in the distribution of GBMT in patients of TBMD and age and sex matched controls. Ultrastructural morphometry is the ultimate and appropriate method for diagnosing TBMD.

Adolescent↗

Incidence of lamivudine resistance associated mutations in pol-gene of HIV-1 in patients from north India: a preliminary report.

Screening of drug-resistant variants is very important for the effective clinical management of HIV-infected patients and development of new strategies. The present study was aimed to detect codon-184 mutations in the pol-gene of HIV leading to resistance to lamivudine (3-TC) by nested cum ARMS-PCR approach in 10 treated and 9 treatment naive patients. For correlation the whole blood CD4/CD8 cell counts and the soluble TNFRII levels in plasma were also determined. Of the 19 patients tested, mutant variants were observed in 2 patients (Met Val in one and Met Val & lle in second) both being treated with 3-TC. No mutations were detected in the treatment-naive patients. The results confirmed that, drug resistant variants of codon-184 emerge rapidly in patients receiving 3-TC containing regimens including our population, which is mainly infected with subtypeC of the virus that could be detected along with wild viral population using sensitive approaches such as ARMS-PCR.

Anti-HIV Agents↗

Cellular and serological markers of disease activity in Indian patients with HIV/AIDS.

There has been an exponential rise of HIV positive patients as observed at the surveillance center of Nehru Hospital. Most patients are poor and cannot afford repeated viral load assays. Therefore, there is a need to identify cost effective and reliable surrogate markers of disease activity. In the present study absolute number of CD4 cells, beta2 micro-globulin, circulating nucleosomes were studied in 30 patients of AIDS, 30 seropositives and 30 healthy controls. In addition viral load, P-24 assay, and TNFR-II assays were done in seropositive and AIDS patients. The mean CD4 cells in patients with AIDS were 69.66 +/- 68.25 mm3 while in seropositives values was 370 +/- 201.29 mm3. The mean CD4 cells in healthy controls were however 690 +/- 198 mm3. The differences in all the groups were highly significant (p<0.001). The mean CD4 values in Indians are significantly lower than reported from the west. The lower number of CD4 cells in healthy population is interpreted to be due to immune activation. The CD8 cell number in controls was 650 +/- 207 mm3 this figure is also higher than that observed in the west. P-24 assay failed to delineate between seropositives and patients with AIDS. Although, beta2 microglobulin levels were significantly higher in AIDS than in seropositives and higher in seropositives than in controls yet with the best possible cut off, it had a sensitivity of only 70% in delineating the two conditions. The correlation between CD4 cells and viral load was more significant when the CD4 cells were below 200 mm3. Five out of 30 patients with a CD4 of 300-600 mm3 had a viral load of over 1 x 10(5) cop/ml. The difference in TNF R-II levels between seropositives and AIDS was however more impressive. With a cut off of 550 pg/ml it had a sensitivity of 95% in delineating HIV from AIDS. It is concluded that a combination of absolute number of CD4 cells and TNF R-II assay along with clinical evaluation may be used to monitor therapy in resource poor countries where frequent viral load assay is unaffordable.

Acquired Immunodeficiency Syndrome↗

Antimicrobial effect of protein(s) isolated from a marine mollusc Telescopium telescopium.

Ammonium sulfate precipitated protein (SF-50) isolated from the spermatheca gland of Telescopium telescopium, an invertebrate marine snail, showed antimicrobial effect on Escherichia coli. The antimicrobial effect varied with the concentration of "SF-50" used and the effect was found to be comparable to antibiotics like amikacin, contrimoxazole and gentamycin in disc diffusion test. The "SF-50" was devoid of erythrocyte haemolysis property.

Animals↗

Immune functions in splenectomized thalassaemic children.

A prospective study to assess the immune functions in splenectomized thalassaemic children. Children were those registered in the Thalassemia major. There were 10 splenectomized children (Group 1), 10 non-splenectomized children and 6 age-matched control (Group 3). All children were shown to be HIV seronegative. The mean concentrations of serum IgG and IgA were higher in Group 1 as compared to Groups 2 and 3 but the differences were not statistically significant. Nitroblue tetrazolium (NBT) dye reduction by stimulated polymorphonuclear leukocytes was normal in both study and control groups and the differences were not statistically significant. However, NBT reduction in the unstimulated state was much higher in Group 2 as compared to Groups 1 and 3. Phytohaemagglutinin induced mitogen proliferation was normal in all 3 groups. Children in Group 1 not only had a significantly higher absolute lymphocyte count but also had a lower CD4/CD8 ratio as compared to Groups 2 and 3. Splenectomy does appear to alter the immune status of thalassemic children but the exact mechanism by which this occurrence is not clear.

Child↗

Characterization of the regulatory region of the human testis-specific form of the pyruvate dehydrogenase alpha-subunit (PDHA-2) gene.

The alpha-subunit of human pyruvate dehydrogenase (E(1)) is encoded by two separate genes. The gene located on chromosome X (PDHA-1) is expressed in somatic tissues, whereas the second gene (PDHA-2), located on chromosome 4, is expressed only in post-meiotic spermatogenic cells. A genomic fragment harboring the human gene encoding PDHA-2 has been isolated and approximately 800 nucleotides of the promoter region have been characterized. Functional studies of the promoter indicate the presence of both enhancer and repressor elements that are common to other genes that are only expressed in mature sperm.

Base Sequence↗

Clinico-immunological profile of juvenile rheumatoid arthritis at Chandigarh.

OBJECTIVE: To study the clinical and immunological profile of children with juvenile rheumatoid arthritis (JRA). DESIGN: Retrospective hospital based study. SETTING: Tertiary level center of North India. SUBJECTS: 74 patients attending the Pediatric Rheumatology and Immunology Clinic over last 5 years. RESULTS: The patients were aged between 9 months to 12 years with male female ratio of 1.8:1. Eleven (14.9%) patients had systemic onset JRA, 28 (37.8%) had polyarticular onset type and 35(47.3%) had pauciarticular onset type JRA. Uveitis was present only in one patient and rheumatoid nodules were present in 4(5.4%) patients. Rheumatoid factor was positive in 2(2.7%) and antinuclear antibody was present in one patient only. HLA-B27 was positive in 4 children. Two patients developed amyloidosis. CONCLUSION: The clinico-immunological profile of JRA at Chandigarh appears to be some what different from that reported from other centers in India.

Age Distribution↗

Neutrophil functions in rheumatoid arthritis.

Neutrophils play an important role in the pathogenesis of rheumatoid arthritis by accumulation and liberation of active proteolytic enzymes. Despite the active participation of the neutrophils, the patients afflicted with rheumatoid arthritis are prone to multiple infections. We studied neutrophil functions in 20 rheumatoid arthritis patients in active disease and equal number in remission and 20 healthy normal controls. No change in neutrophil function was seen in patients in remission. Phagocytic capacity of the neutrophils in active disease was found to be significantly reduced (p < 0.05). This inversly correlated with the rheumatoid factor (r = -0.128, p = 1). Random migration and chemotaxis was statistically reduced when compared with either healthy controls (p < 0.01) or when compared with patients in remission (p < 0.01). The chemotaxis inhibition was further enhanced by autologus serum (p < 0.05). The serum from patients with active disease also reduced chemotaxis of neutrophils from normal individuals (p < 0.01), indicating reduced cellular response as well as inhibitors in serum. The positive correlation (r = 0.466, p < 0.01) with rheumatoid factor, suggests the inhibitory activity may be due to the circulating rheumatoid factor in the active disease. The postulate that prior saturation of neutrophil receptors with immune complexes lower phagocytosis as well as chemotaxis is sustained. Destruction of chemotaxis receptors by release of various strong oxidative enzymes by neutrophils may also be a factor. Normal leucocytes are seen to take up immunoglobulins from diseases serum but not from normal serum. This uptake of diseased serum may be responsible for reducing the chemotactic and phagocytic function of neutrophils and hence increased incidence of infection in these patients.

Adult↗

Concurrent elevation of the levels of expression of striatal preproenkephalin and preprodynorphin mRNA in the rat brain by chronic treatment with caffeine.

Caffeine is a widely consumed substance that elicits psychomotor stimulant effects and also displays addictive properties. In order to assess the effect of caffeine on striatal neuropeptide mRNA expression, male rats were injected (i.p.) with caffeine at 20, 40 or 80 mg/kg of body weight twice daily for 9 consecutive days. Preproenkephalin (PPE), preprotachykinin A (PPT-A) and preprodynorphin (PPD) mRNA levels were determined in coronal sections of brain tissue by in situ hybridization histochemistry. PPE mRNA levels were increased by chronic caffeine in all subdivisions of the striatum at 80 mg/kg (dorsolateral caudate-putamen (dlCPu), +139%; dorsomedial CPu (dmCPu), +42%; ventrolateral CPu (vlCPu), +102%; ventromedial CPu (vmCPu), +20%; and anterior CPu (aCPu), +75% relative to vehicle-injected controls that were normalized to 0% change). Similarly, PPD mRNA expression was increased in all aspects of the striatum at 80 mg/kg (dlCPu, dmCPu, vlCPu, vmCPu and aCPu, +98%, +25%, +104%, +9% and +85%, respectively). In contrast to PPE mRNA, PPD mRNA was increased +117% above control in the nucleus accumbens (NAc) at 20 mg/kg of caffeine. PPT-A mRNA expression was not significantly affected by caffeine treatment in the CPu or NAc. The data demonstrate that repeated exposure to caffeine selectively increases opioid neuropeptide mRNA expression in the striatum and the NAc of the rat brain by a dopamine-independent mechanism.

Animals↗

Low sensitivity of counter-current immuno-electrophoresis for serodiagnosis of typhoid fever.

Counter-current immuno-electrophoresis was evaluated as a diagnostic test for the serodiagnosis of typhoid fever with somatic (O), flagellar (H) and capsular polysaccharide (Vi) antigens of Salmonella typhi on the sera of patients who were blood culture positive (confirmed typhoid cases) or had high Widal agglutination titres, > or = 320, (presumptive typhoid cases). Of the 37 sera from confirmed cases, 30% showed positivity with O antigen, 24% with H antigens and 51% with Vi antigen. In patients with a presumptive diagnosis, 45% were positive for O antibody, 27% for flagellar antibody and 52% for Vi antibody. When all three antigens were combined the reactivity to any of the antigens was found to be 59% in confirmed typhoid cases, 79% in presumptive typhoid cases and 93% in patients who were simultaneously positive by blood culture and Widal agglutination. However, none of the sera from 45 controls gave a positive precipitation reaction with any of the antigens. It is concluded that counter-current immuno-electrophoresis is a rapid test with low sensitivity and high specificity with Vi antigen, a panel of antigens being most effective, and is, therefore, recommended for rapid diagnosis of typhoid fever.

Agglutination Tests↗

Inhibition of host cell transcription by poliovirus: cleavage of transcription factor CREB by poliovirus-encoded protease 3Cpro.

Host cell RNA polymerase II-mediated transcription is inhibited by poliovirus infection. Previous studies from our laboratory showed that activated transcription from a cyclic AMP-responsive element (CRE)-containing promoter was severely inhibited in extracts prepared from poliovirus-infected HeLa cells compared to those from mock-infected cells. Here we demonstrate that the CRE-binding protein, CREB, is specifically cleaved by the poliovirus-encoded protease 3Cpro both in vitro and in virus-infected cells. The proteolytic cleavage of CREB leads to a significant loss of its DNA binding as well as transcriptional activity. Additionally, we demonstrate that the phosphorylated, transcriptionally active form of CREB is cleaved by the viral protease in vitro. The results presented here suggest that a direct cleavage of CREB by the viral protease 3Cpro leads to inhibition of CREB-activated transcription in poliovirus-infected HeLa cells.

Amino Acid Sequence↗

Accumulation of tyrosine hydroxylase messenger RNA molecules in the rat mesencephalon by chronic caffeine treatment.

In the present study we assessed the effect of chronic treatment with caffeine on the levels of the messenger RNA molecule encoding the enzyme tyrosine hydroxylase (TH) by in situ hybridization histochemistry in the ventral tegmental area (VTA) and the substantia nigra compacta (SNc) of the rat brain. Animals that received caffeine for nine consecutive days at doses of 20, 40 and 80 mg/kg of body weight displayed increased TH mRNA levels in the SNc (up to 64% above vehicle-injected controls) and the VTA (33% above controls). Moreover, the increases observed at 80 mg/kg of caffeine were prevented by concurrent administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (0.25 mg/kg). These results demonstrate that chronic exposure to caffeine, an adenosine A2 receptor antagonist, alters the levels of expression of the mRNA encoding the rate limiting enzyme in catecholamine biosynthesis.

Animals↗

Biology of Saryupari Brahmins of Chhattisgarh, central India.

In July-November, 1986, Saryupari Brahmins of Chhattisgarh (Central India) have been investigated for the distribution of ABO blood groups, Rh factor, ABH secretion, PTC taste sensitivity and seven morphological traits. The important findings in brief are as follows: 1. The frequency of O blood group is slightly dominant (38.91%) and gene frequency exhibit r > q > p pattern. Statistical analysis (D/sigma = 0.5447) show that the population is in genetic equilibrium. 2. Estimation of the expected rate of erythroblastosis foetalis occurred in this population is calculated to be 8-16 cases in every 10,000 pregnancies. 3. High incidence (53.82%) of non-secretors of ABH substances in saliva suggest that this group may belong to Caucasoid stock. 4. The ability to taste the chemical PTC has a high frequency (61.81%) in this group. 5. R/L type of handclasping (58.15%), leg folding (65.38%) and L/R type of arm folding (58.93%) is dominant. L-type of handedness (5.48%) is moderately high. 6. Tongue rollers (93.28%) and folders (53.77%) are more among them. 7. Free type of ear lobe (68.68%) is the common feature in this population. 8. The above observations were compared in details with other Brahmin populations reported from India with special reference to the descendant groups residing in Madhya Pradesh (Central India). Furthermore, the results obtained on growth studies, and dermatoglyphic studies (palm and sole) from our published literature were also included so as to have some idea on the genetical, behavioural, dermatoglyphic and growth norms of this group.

ABO Blood-Group System↗

Paraproteins and plasma cell dyscrasias.

Serum protein electrophoresis done on 1100 patients with various diseases in one year demonstrated M-band in 31 patients. Most (87%) had the classical features of plasma cell dyscrasia (PCD), however a few had unusual presentations which are highlighted. A 22-year-old male operated for a massive tumour of the scapula clinically diagnosed as chondrosarcoma revealed plasmacytoma with amyloid on histology. Another case of kala-azar presented with features akin to that of PCD and one case had dual malignancies. Such a high incidence of PCDs with varied picture in a short time is not usually seen in other parts of this country; a fact which may be due to lack of awareness.

Adult↗

Expression and subcellular localization of poliovirus VPg-precursor protein 3AB in eukaryotic cells: evidence for glycosylation in vitro.

The poliovirus-encoded, membrane-associated VPg-precursor polypeptide 3AB has been implicated in the initiation of viral RNA synthesis. We have expressed 3AB and 3A polypeptides in eukaryotic cells and examined their localization using indirect immunofluorescence and a direct in vitro membrane-binding assay. Results presented here demonstrate that both 3AB and 3A are capable of localizing in the endoplasmic reticulum and the Golgi apparatus in transfected HeLa cells in the absence of any other poliovirus protein. We have also shown that the carboxy-terminal 18 amino acids of 3A that constitute an amphipathic domain are important in membrane binding of 3A and 3AB. Additionally, we demonstrate that a significant fraction of both 3A and 3AB can be glycosylated in a membrane-dependent fashion during in vitro translation in reticulocyte lysate. We demonstrate that 6-diazo-5-oxo-L-norleucine, an inhibitor of glycoprotein synthesis, significantly inhibits poliovirus RNA synthesis in vivo. The implications of glycosylation of 3AB (and 3A) in viral replication are discussed.

Base Sequence↗

Importance of bone marrow culture for diagnosis of Kala azar.

Kala azar was diagnosed in 45 clinically suspected cases following bone marrow smear examination and in vitro culture of the aspirate. Bone marrow aspiration smear examination revealed amastigotes in 27 cases (60%). In vitro culture of the aspirate demonstrated leishmania parasites in 44 cases (97.8%). A total of 18 cases (40%) were negative for amastigotes in smear examinations but parasites could be demonstrated by culturing the same aspirates. The in vitro culture of bone marrow is necessary to diagnose Kala azar and is strongly recommended to be performed along with the bone marrow smear examination.

Adolescent↗

Immunoglobulin deficiency.

Twenty three patients with primary immunoglobulin(Ig) deficiency were seen during the last ten years. Nine had hypogamma globulinemia (hypo-Ig) and the rest, selective Ig deficiency. Most were in pediatric age group. There was preponderance of males with only one female. Clinical symptoms pertaining to gastrointestinal and sinupulmonary infections were most common. Complete absence of B cells was not observed in any patient with hypogammaglobulinemia. They could be typed as physiological in one patient, X-linked immunodeficiency in 2 patients and common variable immunodeficiency in the remaining six. Three patients with selective IgA deficiency were above 20 years of age. Two had only secretory IgA deficiency, confirmed by jejunal fluid examination and the rest had both secretory and serum IgA deficiency. Low IgM was seen in one patient. We see a spectrum of immunoglobulin deficiencies varying from subtle defects like absence of secretory IgA only, to severe depletion of all immunoglobulins. Therapy is still not ideal due to economic reasons.

Adolescent↗