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Biomedical subjects

S Bhattacharya

Publications and source records attributed to S Bhattacharya.

At least 217 records · Page 12Linked to original sources
PubMed1998

Anterior polar cataract: clinical spectrum and genetic linkage in a single family.

Anterior polar cataract can occur as a sporadic finding, in association with other ocular abnormalities or as an inherited, autosomal dominant disorder. We have demonstrated linkage in a family with autosomal dominant anterior polar cataract to the short arm of chromosome 17, locating the gene to the region 17p12-13. All affected members of this large family had an opacity at the anterior pole of the lens that varied only in size and the effect on visual acuity. Anterior polar cataract is thought to have a minimal effect on visual acuity although in the affected members of this family there was a high incidence of unilateral amblyopia.

Cataract↗
PubMed1998

Characterization of cationic lipid-protamine-DNA (LPD) complexes for intravenous gene delivery.

A previous study has shown an efficient, systemic transgene expression in mice via intravenous administration of a LPD formulation composed of DOTAP liposomes, protamine sulfate and plasmid DNA. In this study, factors affecting the in vivo performance of this formulation were further evaluated. A protocol in which liposomes were mixed with protamine before the addition of plasmid DNA was shown to produce small condensed particles with a diameter of about 135 nm. These particles were stable over time and gave a high level of gene expression in all tissues examined including lung, heart, spleen, liver and kidney with the highest level of expression in the lung. Inclusion of dioleoylphosphatidylethanolamine (DOPE) as a helper lipid significantly decreased the in vivo activity of LPD. In contrast, inclusion of cholesterol as a helper lipid increased the in vivo transfection efficiency of LPD and more importantly, decrease the amount of cationic lipid required for the maximal level of gene expression. Studies on the interaction between mouse serum and LPD showed that LPD became negatively charged after exposure to serum, and LPDs containing different helper lipids varied in the amount of associated serum proteins. LPD containing DOPE was more enriched in a protein corresponding to albumin in molecular weight. These results suggest that the mechanism of LPD-mediated intravenous gene delivery might be different from that of in vitro lipofection and that serum protein association might be a major factor limiting the in vivo transfection by LPD.

Animals↗
PubMed1998

A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q.

CZP1, a locus for autosomal dominant "zonular pulverulent" cataract, previously had been linked with the Duffy blood-group-antigen locus on chromosome 1q. Here we report genetic refinement of the CZP1 locus and show that the underlying mutation is present in GJA8, the gene for connexin50. To map the CZP1 locus we performed linkage analysis using microsatellite markers on two distantly related branches of the original Ev. pedigree, which now spans eight generations. Significantly positive two-point LOD score (Z) values were obtained for markers D1S2669 (maximum Z [Zmax] = 4.52; maximum recombination frequency [thetamax] = 0) and D1S514 (Zmax = 4.48; thetamax = 0). Multipoint analysis gave Zmax = 5.22 (thetamax = 0) at marker D1S2669. Haplotyping indicated that CZP1 probably lies in the genetic interval D1S2746-(20.6 cM)-D1S2771. Sequence analysis of the entire protein-coding region of the GJA8 gene from the pedigree detected a C-->T transition in codon 88, which introduced a novel MnlI restriction-enzyme site that also cosegregated with the cataract. This missense mutation is predicted to result in the nonconservative substitution of serine for a phylogenetically conserved proline (P88S). These studies provide the first direct evidence that GJA8 plays a vital role in the maintenance of human lens transparency and identify the genetic defect believed to underlie the first inherited disease to be linked to a human autosome.

Cataract↗
PubMed1998

Mutations of the forkhead/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly.

Genetic linkage, genome mismatch scanning, and analysis of patients with alterations of chromosome 6 have indicated that a major locus for development of the anterior segment of the eye, IRID1, is located at 6p25. Abnormalities of this locus lead to glaucoma. FKHL7 (also called "FREAC3"), a member of the forkhead/winged-helix transcription-factor family, has also been mapped to 6p25. DNA sequencing of FKHL7 in five IRID1 families and 16 sporadic patients with anterior-segment defects revealed three mutations: a 10-bp deletion predicted to cause a frameshift and premature protein truncation prior to the FKHL7 forkhead DNA-binding domain, as well as two missense mutations of conserved amino acids within the FKHL7 forkhead domain. Mf1, the murine homologue of FKHL7, is expressed in the developing brain, skeletal system, and eye, consistent with FKHL7 having a role in ocular development. However, mutational screening and genetic-linkage analyses excluded FKHL7 from underlying the anterior-segment disorders in two IRID1 families with linkage to 6p25. Our findings demonstrate that, although mutations of FKHL7 result in anterior-segment defects and glaucoma in some patients, it is probable that at least one more locus involved in the regulation of eye development is also located at 6p25.

Amino Acid Sequence↗
PubMed1998

A new family of Greek origin maps to the CRD locus for autosomal dominant cone-rod dystrophy on 19q.

Retinal photoreceptor dystrophies (RD) are a highly heterogeneous group of genetic disorders of the retina, representing the most frequently inherited form of visual handicap, affecting approximately 1.5 million people world wide. To date, more than 40 genetic loci have been implicated in RD. One of them, the CORD2 locus, for an autosomal dominant form of cone-rod dystrophy (CRD), maps to chromosome 19q and has previously been reported in a single large family of British origin. We now report a new family with severe early onset CRD, phenotypically very similar to the British family, which also maps to 19q, but is of Greek origin. Haplotype data of the Greek family showed no recombination between and including markers D19S219 and D19S246 and linkage analysis gave a lod score of 2.7 (at theta=0) with marker D19S412, confirming the data obtained in the British family.

Chromosome Mapping↗
PubMed1998

Thyroid hormone stimulates progesterone release from human luteal cells by generating a proteinaceous factor.

Blood samples collected from 29 women (aged between 19 and 35 years) during the luteal phase of the menstrual cycle (between days 18 and 23 of the cycle) showed that deficiency in thyroid hormone level is related to a decrease in progesterone (P4) secretion. To observe the effect of thyroid hormone on human ovarian luteal cells, 3,5,3'-triiodothyronine (T3; 125 ng/ml) was added to luteal cells in vitro. T3 significantly stimulated progesterone release (P < 0.01) from luteal cells and this could be blocked by cycloheximide, indicating a protein mediator for the T3 effect. The T3 stimulatory effect was inhibited by anti-T3 antibody suggesting specificity of T3 action. Addition of T3 caused a more than threefold increase in cellular protein synthesis which was inhibited by cycloheximide. Preparation of partially purified thyroid hormone-induced factor (TIF) (from peak II of Sephadex G 100 chromatography of T3-incubated cells), and its addition to luteal cell incubations caused a significant increase in P4 release (P < 0.05). Incubation with trypsin or treatment with heat destroyed the stimulatory effect of TIF on P4 release, indicating the proteinaceous nature of TIF. Purified thyroid hormone-induced protein. (TIP) from rat granulosa cells and fish ovarian follicles greatly stimulated P4 release from human luteal cells. These results suggest that T3 stimulation of P4 release from human luteal cells is not direct, but is mediated through a putative protein factor, which appears to be a protein conserved through evolution as far as its biological activity is concerned.

Adult↗
PubMed1998

Trianthema portulacastrum restores the antioxidant defense enzyme levels and hepatic biotransformation patterns in experimental rat hepatocarcinogenesis.

The chloroform fraction of Trianthema portulacastrum L. has been found to be very effective in restoring glutathione levels and the levels of Phase I (cytochrome P-450 monooxygenase) and Phase II (UDPGT) enzymes, which undergo substantial changes during chemical rat hepatocarcinogenesis. Experimental heptocarcinogenesis was initiated by a single i.p. injection of Diethylnitrosoamine (DENA) at a dose of 200 mg/kg body weight in 0.9% normal saline. A single administration of the carcinogen is adequate to evoke the appearance of a neoplasm after 22 weeks. Various fractions of T. portulacastrum (crude aqueous, [ethanolEtOH] fraction, chloroform-fractions) in the form of plant extracts were administered to the control as well as to the experimental animals at a dose of 100 mg/kg body weight to the basal medium. After 22 weeks on this regimen, animals were sacrificed, and the different biomarkers were assayed from the hepatic tissues. The results obtained after treatment with the chloroform extract of T. portulacastrum were remarkable. The ethanol and crude aqueous extracts were less effective. Ethanol control, chloroform controls and Trianthema controls displayed similar values as that of normal untreated animals with regard to the different parameters tested. Our findings reflect strong anticarcinogenic potential of the chloroform extract of T. portulacastrum as far as these important biomakers are concerned.

Animals↗
PubMed1998

FNAC diagnosis of tuberculosis--an eight years study at Mangalore.

1. FNAC is a very useful adjunct in the diagnosis of tuberculosis: 2. Diagnosis of tuberculosis can be made by the demonstration of epithelioid granulomas with or without caseation even in the absence of AFB. 3. Necrotic features whether acellular or accompanied by neutrophilic infiltrate are usually misdiagnosed as suppurative abscesses. Such smears however show high AFB positivity and thus the diagnosis of tuberculosis is still possible even in the absence of epithelioid granulomas. 4. Therefore all smears obtained by FNAC of suspected tuberculous lesions should be subjected to ZN staining for AFB.

Adolescent↗
PubMed1998

Prednisolone-induced alteration in hepatic and muscular protein and glycogen level: its correlation with blood glucose level in mice.

Prednisolone, a potent glucocorticoid, is well known for its immunosuppressive effects on animals. A single dose of 100 microg, 200 microg and 300 microg prednisolone/kg body weight was administered in Swiss albino male mice. Seven days after treatment, the animals were sacrificed to investigate the effect of prednisolone on hepatic and muscular protein contents and glycogen levels along with the level of blood glucose. A catabolic effect on the protein level was evidenced but at the same time the mice became hypoglycemic.

Animals↗
PubMed1998

Clinical profile of myasthenia gravis.

Seventy three patients with myasthenia gravis were studied over 9 years period (1987-1995) in departments of neuromedicine, respiratory care unit, cardiothoracic unit of Institute of Postgraduate Medical Education and Research and Bangur Institute of Neurology, Calcutta, with reference to their clinical presentations, laboratory findings and various modes of treatment. Commonest age of presentation was 5th decade in men and 3rd decade in women. Fifty five percent of patients belong to type 2A myasthenia gravis (Osserman classification). Presentation was insidious (67.2%) and course was slowly progressive (65.7%) in majority of cases. Fatigability and ptosis were commonest clinical presentation and diurnal variation was noticed in 60% of cases. Edrophonium test was positive in 90.4% of cases and repetitive nerve stimulation showed 93.5% positivity in 30 cases. 27 patients (36.9%) underwent thymectomy and out of these, 89% of patients showed hyperplastic change and thymoma in 11% of cases. Mortality rate including both operated and nonoperated patients was recorded to be 9.6%. We observed earlier onset of myasthenia in male, higher incidence of oculo-bulbar involvement and lower incidence of respiratory problem and thymoma.

Adolescent↗
PubMed1998

Role of DNA probes in characterization of pathogenic and non-pathogenic E. histolytica.

Various tests have been described to differentiate the pathogenic and non-pathogenic types of E. histolytica. Recently DNA hybridization has been described to differentiate between the two subtypes. Using common HMC probe the presence of E. histolytica in stool was confirmed. Then on the basis of hybridization with DNA probe P 145 (pathogenic) and B 133 (non-pathogenic) E. histolytica was characterized as being pathogenic and non pathogenic respectively. Out of 137 patients studied 88 were symptomatic and 49 asymtomatic. 65 patients harboured E. histolytica as proved by microscopic examination of stool. Sixty-eight stool samples tested positive for DNA hybridization with common HMC probe, this included 65 microscopy positive samples and 3 microscopy negative samples. This gives a sensitivity of 100% and 96% specificity. All the 68 samples were then subjected to hybridization with P 145 and B 133 DNA probes. Out of 88 symptomatic patients stool samples of 57 patients were microscopy positive, however 58 were positive by common HMC probe and all of these were P 145 (pathogenic) positive and B 133 (non-pathogenic) negative. Of the 49 asymptomatic cases 8 were E. histolytica positive on microscopy and 10 positive on hybridization with common HMC probe and all 10 were P 145 negative and B 133 positive. It can be thus concluded that DNA hybridization is a reliable way to differentiate between pathogenic and nonpathogenic E. histolytica.

Animals↗
PubMed1998

Prognostic significance of peripheral blood and bone marrow tyrosinase messenger RNA in malignant melanoma.

The objectives of this study were to evaluate the prognostic significance of reverse transcription PCR (RT-PCR) detection of tyrosinase mRNA in the peripheral blood (PB) and bone marrow (BM) of patients with stage II-IV malignant melanoma (MM). Seventy-three PB samples and 109 BM aspirates from 123 assessable patients with stage II-IV MM were analyzed for tyrosinase mRNA using nested RT-PCR. Twenty-five controls without MM were also evaluated. The RT-PCR results were correlated with overall survival (OS) and clinical stage. Overall, 23 of the 123 patients with MM (19%) had tyrosinase mRNA in their blood and/or BM. RT-PCR positivity was present in the PB of 9 of 73 patients (12%), whereas 18 of 109 (16.5%) had tyrosinase mRNA in their BM. All controls were tyrosinase PCR negative. There was no correlation between RT-PCR results and clinical stage. Within stage II, BM PCR-positive patients had a shorter median survival (24 months) than BM PCR-negative individuals (median not reached), with a P approaching significance (P = 0.06). There was a statistically significant correlation between blood PCR positivity and decreased overall survival (P = 0.03) in all patients. Blood PCR positivity was associated with a significantly decreased OS in stage II and III (P = 0.01 and 0.02, respectively) and was not a predictor of OS in stage IV. In multivariate analysis, blood RT-PCR for tyrosinase mRNA was found to be an independent predictor of survival (P = 0.03; risk ratio, 2.87). RT-PCR can specifically detect tyrosinase mRNA in the PB and BM of patients with MM. Blood RT-PCR is an independent predictor of overall survival in stage II-III MM. Additional studies are needed to define the potential role of this assay in the management of patients with advanced melanoma.

Adult↗
PubMed1998

Serology and immunoglobulin profile in rheumatoid arthritis.

One hundred and twenty cases of clinically diagnosed rheumatoid arthritis, 80 non-rheumatoid cases suffering from various other diseases and 40 healthy individuals were investigated for the presence of rheumatoid factor, quantitation of serum immunoglobulin, demonstration of ANA and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid factor showed 56.6% positivity in rheumatoid group and 3.7% positivity in non-rheumatoid group. All three serum immunoglobulins (IgG, IgM, IgA) were raised in serum in significant titre in cases of rheumatoid arthritis, whereas only IgA lever was elevated in the group of non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 11.7% and 4.4% cases of rheumatoid arthritis who had severe underlying disease. In non-rheumatoid group, only one of 6 cases of systemic lupus erythematosus showed rheumatoid factor and that too in an insignificant titre (less than 1:20). Synovium and synovial fluid contained plenty of plasma cells and lymphocytes. It has been observed that RF appears first in synovial fluid and it may take several months to a year to attain detectable level in serum.

Adolescent↗
PubMed1997

Thermodynamics of metal ion binding and denaturation of a calcium binding protein from Entamoeba histolytica.

The thermodynamics of the binding of calcium and magnesium ions to a calcium binding protein from Entamoeba histolytica was investigated by isothermal titration calorimetry (ITC) in 20 mM MOPS buffer (pH 7.0) at 20 degrees C. Enthalpy titration curves of calcium show the presence of four Ca2+ binding sites. There exist two low-affinity sites for Ca2+, both of which are exothermic in nature and with positive cooperative interaction between them. Two other high affinity sites for Ca2+ exist of which one is endothermic and the other exothermic, again with positive cooperative interaction. The binding constants for Ca2+ at the four sites have been verified by a competitive binding assay, where CaBP competes with a chromophoric chelator 5,5'-Br2 BAPTA to bind Ca2+ and a Ca2+ titration employing intrinsic tyrosine fluorescence of the protein. The enthalpy of titration of magnesium in the absence of calcium is single site and endothermic in nature. In the case of the titrations performed using protein presaturated with magnesium, the amount of heat produced is altered. Further, the interaction between the high-affinity sites changes to negative cooperativity. No exchange of heat was observed throughout the addition of magnesium in the presence of 1 mM calcium. Titrations performed on a cleaved peptide comprising the N-terminus and the central linker show the existence of two Ca2+ specific sites. These results indicate that this CaBP has one high-affinity Ca-Mg site, one high-affinity Ca-specific site, and two low-affinity Ca-specific sites. The thermodynamic parameters of the binding of these metal ions were used to elucidate the energetics at the individual site(s) and the interactions involved therein at various concentrations of the denaturant, guanidine hydrochloride, ranging from 0.05 to 6.5 M. Unfolding of the protein was also monitored by titration calorimetry as a function of the concentration of the denaturant. These data show that at a GdnHCl concentration of 0.25 M the binding affinity for the Mg2+ ion is lost and there are only two sites which can bind to Ca2+, with substantial loss of cooperativity. At concentrations beyond 2.5 M GdnHCl, at which the unfolding of the tertiary structure of this protein is observed by near UV CD spectroscopy, the binding of Ca2+ ions is lost. We thus show that the domain containing the two low-affinity sites is the first to unfold in the presence of GdnHCl. Control experiments with change in ionic strength by addition of KCl in the range 0.25-1 M show the existence of four sites with altered ion binding parameters.

Amino Acid Sequence↗
PubMed1997

Interaction of surfactants with DNA. Role of hydrophobicity and surface charge on intercalation and DNA melting.

A probe, 9-(anthrylmethyl)trimethylammonium chloride, 1. was prepared, 1 binds to caF-thymus DNA or Escherichia coli genomic DNA with high affinity, as evidenced from the absorption titration. Strong hypochromism, spectral broadening and red-shifts in the absorption spectra were observed. Half-reciprocal plot constructed from this experiment gave binding constant of 5 +/- 0.5 x 10(4) M-1 in base molarity. We employed this anthryl probe-DNA complex for studying the effects of addition of various surfactant to DNA. Surfactants of different charge types and chain lengths were used in this study and the effects of surfactant addition to such probe-DNA complex were compared with that of small organic cations or salts. Addition of either salts or cationic surfactants led to structural changes in DNA and under these conditions, the probe from the DNA-bound complex appeared to get released. However, the cationic surfactants could induce such release of the probe from the probe-DNA complex at a much lower concentration than that of the small organic cations or salts. In contrast the anionic surfactants failed to promote any destabilization of such probe-DNA complexes. The effects of additives on the probe-DNA complexes were also examined by using a different technique (fluorescence spectroscopy) using a different probe ethidium bromide. The association complexes formed between the cationic surfactants and the plasmid DNA pTZ19R, were further examined under agarose gel electrophoresis and could not be visualized by ethidium bromide staining presumably due to cationic surfactant-induced condensation of DNA. Most of the DNA from such association complexes can be recovered by extraction of surfactants with phenol-chloroform. Inclusion of surfactants and other additives into the DNA generally enhanced the DNA melting temperatures by a few degrees C and at high [surfactant], the corresponding melting profiles got broadened.

Animals↗
PubMed1997

Small hepatocellular carcinomas in cirrhotic explant livers: identification by macroscopic examination and lipiodol localization.

Small hepatocellular carcinomas (HCCs) in cirrhotic livers are difficult to detect. This study aimed to assess if small HCCs can be better identified using specific macroscopic sampling criteria and Lipiodol (iodized oil) localization on radiographs, and to evaluate thereby their incidence and morphology. Prospective cirrhotic recipients of orthotopic liver transplantation (OLT) were administered hepatic arterial Lipiodol at angiography. Posttransplantation, the explant livers were sliced and inspected as per routine for unusual nodules. If unusual nodules were found or HCC clinically suspected, the slices underwent soft-tissue radiography. Tissue samples were then taken as per protocol from all nodules with diameter > or =1 cm/unusual appearance/exophytic bulge, and from foci of radiographic Lipiodol uptake or high soft-tissue density. One hundred three lesions were assessed and classified histologically as HCC (n = 55) or regenerative nodule (n = 39) or borderline (n = 9). Sampling according to predetermined macroscopic criteria proved an effective method for identifying small HCCs: 44 cancers were detected, most <5 mm in diameter, additional to those picked up on routine assessment. Green nodules were more likely to be HCC (P < .0001). The cancers were all multifocal, and had characteristic histological features of HCC except for 12 unusual fibrotic cancers in livers with alcoholic cirrhosis. Lipiodolization alone identified one additional HCC. Lipiodol retention on x-ray is fairly specific for HCC (83%), and can even identify lesions 2 mm in diameter. But its sensitivity is poor (45%), and its routine use to identify HCCs in explant livers is not recommended.

Carcinoma, Hepatocellular↗
PubMed1997

Retinitis pigmentosa locus on 17q (RP17): fine localization to 17q22 and exclusion of the PDEG and TIMP2 genes.

This group has previously reported the mapping of a novel locus for autosomal dominant retinitis pigmentosa (adRP) in a South African kindred to 17q. Using a new series of microsatellite markers in this study, twopoint and multipoint analysis provide evidence for the localization of the disease gene to the 17q22 region. In addition, a second South African adRP family is shown to be linked to this 17q22 locus. Disease-associated haplotypes constructed for both families and multipoint linkage analysis place the gene in the 10-cM interval between D17S1607 and D17S1874. Three candidate genes on 17q were investigated: PDEG, the gamma subunit of rod phosphodiesterase; TIMP2, tissue inhibitor of metalloproteinases-2; and PRKCA, protein kinase C alpha. Recombination events between the adRP locus and: (1) a single-stranded conformation polymorphism in PDEG; and (2) a restriction fragment length polymorphism in TIMP2 provided evidence for the exclusion of these candidate genes as being responsible for adRP in the South African kindred.

3',5'-Cyclic-GMP Phosphodiesterases↗