Forty years under the central dogma.
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Animals↗
Biomedical subjects
S Sarkar
Publications and source records attributed to S Sarkar.
Lipid peroxidative damage on cadmium exposure and alterations in antioxidant system in rat erythrocytes: a study with relation to time.
Cadmium induced lipid peroxidation (LPO) and the activity of antioxidant enzymes after the administration of a single dose of CdCl2 (0.4 mg kg-1 body wt, i.p.) was studied in rat erythrocytes. Cd intoxication increased erythrocyte LPO along with a decrease in superoxide dismutase (SOD) up to three days of Cd treatment. The decrease in erythrocyte catalase (CAT) activity was marked within 9 h of Cd intoxication. After three days of Cd treatment, LPO decreased towards normal, along with an increase in erythrocyte SOC and CAT activity. Blood glutathione (GSH) decreased significantly within 24 h of Cd treatment, followed by an increase towards normal. Erythrocyte glutathione S-transferase (GST) activity increased up to 10 days of Cd intoxication, probably in an attempt to reduce Cd toxicity. Serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP) and serum bilirubin increased up to 10 days of Cd intoxication. Blood urea increased significantly up to three days, followed by a decrease towards normal. The results show that Cd induced LPO was associated with a decrease in antioxidant enzymes and GSH in erythrocytes; as these antioxidants increase in erythrocytes with recovery from Cd intoxication, the Cd induced LPO reversed towards normal. The increase in the SGPT, SALP and serum bilirubin correlated with LPO. The results suggest that Cd intoxication induces oxidative stress and alters the antioxidant system, resulting in oxidative damage to rat erythrocytes.
Alanine Transaminase↗
tRNA nuclear export in saccharomyces cerevisiae: in situ hybridization analysis.
To understand the factors specifically affecting tRNA nuclear export, we adapted in situ hybridization procedures to locate endogenous levels of individual tRNA families in wild-type and mutant yeast cells. Our studies of tRNAs encoded by genes lacking introns show that nucleoporin Nup116p affects both poly(A) RNA and tRNA export, whereas Nup159p affects only poly(A) RNA export. Los1p is similar to exportin-t, which facilitates vertebrate tRNA export. A los1 deletion mutation affects tRNA but not poly(A) RNA export. The data support the notion that Los1p and exportin-t are functional homologues. Because LOS1 is nonessential, tRNA export in vertebrate and yeast cells likely involves factors in addition to exportin-t. Mutation of RNA1, which encodes RanGAP, causes nuclear accumulation of tRNAs and poly(A) RNA. Many yeast mutants, including those with the rna1-1 mutation, affect both pre-tRNA splicing and RNA export. Our studies of the location of intron-containing pre-tRNAs in the rna1-1 mutant rule out the possibility that this results from tRNA export occurring before splicing. Our results also argue against inappropriate subnuclear compartmentalization causing defects in pre-tRNA splicing. Rather, the data support "feedback" of nucleus/cytosol exchange to the pre-tRNA splicing machinery.
Biological Transport↗
Application of magnetic resonance imaging for evaluation of the efficacy of SB 217242 in neointimal formation.
Although several factors have been implicated in the pathophysiology of vascular neointimal formation and restenosis after balloon angioplasty, current therapies have failed to alleviate these conditions. Because endothelin-1 (ET-1) has been implicated in the pathogenesis of the neointimal growth, this study examined the in vivo efficacy of SB 217242, a potent nonpeptide mixed ETA/ETB receptor antagonist with high oral bioavailability, in the rat carotid balloon angioplasty model. A novel magnetic resonance imaging (MRI) approach was used for evaluation. MRI is a high-resolution, noninvasive spatial imaging modality that can serially monitor arterial luminal caliber in vivo, along with histologic evaluation. In vivo luminal volumes for the left carotid artery (LCA) were measured by MRI at baseline (before surgery) and again at 14 days after angioplasty. SB 217242 (30 mg/kg/day p.o.) was administered daily for 14 days after angioplasty. On day 14, SB 217242 provided 20% protection (p < 0.05) on neointimal-mediated decrease in luminal volume as measured by MRI. The non-ballooned right carotid arteries of both groups had significantly increased luminal volume on day 14 with respect to baseline values, indicating compensation for the decreased luminal size of the LCA. Histologic analysis of the mean intimal-to-medial ratio demonstrated that SB 217242 provided 42% (p < 0.05) protection. These results demonstrate that ET receptor antagonism can inhibit neointimal formation after balloon angioplasty and that MRI technology can provide valuable insight for noninvasive assessment of vascular lesion development.
Angioplasty, Balloon↗
A vision-based technique for objective assessment of burn scars.
In this paper a method for the objective assessment of burn scars is proposed. The quantitative measures developed in this research provide an objective way to calculate elastic properties of burn scars relative to the surrounding areas. The approach combines range data and the mechanics and motion dynamics of human tissues. Active contours are employed to locate regions of interest and to find displacements of feature points using automatically established correspondences. Changes in strain distribution over time are evaluated. Given images at two time instances and their corresponding features, the finite element method is used to synthesize strain distributions of the underlying tissues. This results in a physically based framework for motion and strain analysis. Relative elasticity of the burn scar is then recovered using iterative descent search for the best nonlinear finite element model that approximates stretching behavior of the region containing the burn scar. The results from the skin elasticity experiments illustrate the ability to objectively detect differences in elasticity between normal and abnormal tissue. These estimated differences in elasticity are correlated against the subjective judgments of physicians that are presently the practice.
Algorithms↗
Low HIV and high STD among commercial sex workers in a brothel in Bangladesh: scope for prevention of larger epidemic.
The present study documents the first systematic assessment of a brothel in Bangladesh in terms of sexually transmitted disease (STD) and human immunodeficiency virus (HIV). A cross sectional study was undertaken on brothel-based commercial sex workers (CSWs) selected systematic random sampling to assess the prevalence of STDs and HIV among CSWs in a brothel setting. Two hundred and ninety-six CSWs were selected from a brothel with a population of 593 women. Following informed consent, endocervical and blood samples were obtained for the diagnosis of genital chlamydia, gonorrhoea, HIV and syphilis respectively. In addition, another 170 consecutive blood samples were collected from the total CSW population for HIV tests. All blood samples for HIV testing were made anonymous by removing patient identifiers before testing. Endocervical specimens were tested by polymerase chain reaction (PCR) for the diagnosis of genital chlamydia and gonorrhoea. Syphilis and HIV infections were diagnosed by serology. One hundred and sixty-nine (57.1%) of the women were Treponema pallidum haemagglutination (TPHA)-positive, 20 (6.8%) of the women were Venereal Disease Research Laboratory (VDRL)-positive at a greater than 1:8 dilution. Eighty-two (28%) of the women were found to be infected either by gonorrhoea or chlamydia. No HIV antibody was found in any of the 466 blood samples. A high prevalence of STDs and low prevalence of HIV in the CSWs in Bangladesh suggest potential for the rapid spread of HIV once it is introduced in this high-risk population. The opportunity to control STD and HIV infection in this population should not be missed, in order to prevent a large epidemic in the future.
Bangladesh↗
India's polio eradication efforts at cross roads.
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Child↗
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↗
Chronic arsenic toxicity in west Bengal--the worst calamity in the world.
Since 1983 large number of people are being encountered with arsenic toxicity due to drinking of arsenic contaminated water (0.05-3.2 mg/l) in 6 districts of West Bengal. Clinical and various laboratory investigations were carried out on 156 patients to ascertain the nature and degree of morbidity and mortality that occurred due to chronic arsenic toxicity. All the patients studied had typical rain drop like skin pigmentation (being inclusion criteria) while thickening of palm and sole were found in 65.5% patients. Other features included weakness (70%), gastro-intestinal symptoms (58.6%), involvement of respiratory system (57.08%) and nervous system (50.6%). Lung function tests showed restrictive lung disease in 53% (9/17) and combined obstructive and restrictive lung disease in 41% (7/17) of patients. Abnormal electromyography was found in 34.8% (10/29) and altered nerve conduction velocity in 34.8% (10/29) of cases. Enlargement of liver was found in 120 cases (76.9%) while splenomegaly in 31.4% cases. Liver function test showed elevated globulin level in 15.8% and alkaline phosphatase in 51.3%, alanine amino transferase (ALT) in 11.8% and aspartate amino transferase (AST) in 27.6% of cases. Evidence of portal hypertension was found in 33.3% patients. Liver biopsy reports of 45 patients showed non-cirrhotic portal fibrosis in 41, cirrhosis in 2 and normal histology in 2 cases. There was no correlation between the quantity of arsenic taken through water and the level of arsenic in hair, nail, liver tissues and the degree of fibrosis. There were 5 deaths of which one had skin cancer. The various non-cancer manifestations which were observed in these patients were much severe than those reported in similar cases in other parts of the world.
Adolescent↗
Myospherulosis of maxillary sinus--a case report with review of literature.
Myospherulosis is a rare condition. The authors report a unique case of this entity arising in paranasal sinus. The review of literature with emphasis on pathogenesis is also discussed.
Adult↗
Clone 10d/BM28 (CDCL1), an early S-phase protein, is an important growth regulator of melanoma.
Retinoic acid (RA) induces growth arrest and differentiation of many different tumor cells. RA activates RA receptors, which function as ligand-dependent transcriptional modulators. S91 murine melanoma cells stop proliferating and then reversibly differentiate into a melanocytic cell type after the administration of RA. The genetic changes that take place during this process serve as an excellent model for the etiology of melanoma. The use of subtractive hybridization techniques yielded several differentially expressed cDNAs that are associated with RA-induced growth arrest. One clone, cyclin D1, is repressed and is probably a differentiation marker. Two other cDNAs represent novel, RA-inducible genes. Expression of another cDNA, clone 10d, is strongly down-regulated. It is the homologue of the human gene BM28 (CDCL1) that is indispensable for entry into S phase and cell division. S91 cells that are permanently transfected with a plasmid that constitutively expresses clone 10d become significantly more resistant to RA, suggesting that repression of this gene is a critical event in RA-induced growth arrest. The use of reverse transcription-PCR for the detection of expression in human melanoma in vitro was performed to study the potential role of clone 10d/BM28 in this disease. It is expressed in 80% of melanoma cell lines but is virtually undetectable in primary melanocytes. The expression of BM28 is not regulated by RA in human, RA-resistant melanoma cells. These results suggest that clone 10d/BM28 functions as an important tumor cell growth promoter. The regulation of clone 10d may be directly mediated by RA receptors, and escape from negative regulation may, thus, contribute to the etiology of melanoma.
Base Sequence↗
B cell responses to a peptide epitope: IV. Subtle sequence changes in flanking residues modulate immunogenicity.
We examined modulation of primary humoral responses to a model synthetic peptide immunogen, peptide PS1CT3, as a consequence of single amino acid substitutions. Two analogues were employed, one in which the amino-terminal histidine (His1, peptide G28CT3) and another in which an internal proline (Pro14, peptide G41CT3) were replaced with glycine residues. Peptide G28CT3 displayed markedly enhanced immunogenicity relative to peptide PS1CT3 in BALB/c mice, whereas peptide G41CT3 was only poorly immunogenic. Nevertheless, in all three cases the mature polyclonal IgG response was predominantly directed against a tetrapeptide segment of sequence Asp-Pro-Ala-Phe between positions 4 and 7 of the sequence. While all three peptides proved equally capable of priming Ag-specific Th cells, they, however, displayed significant differences in their abilities to recall T cell responses. Regardless of the priming immunogen, in vitro challenge with either PS1CT3 or its analogues consistently gave a hierarchy of potencies as G28CT3 > PS1CT3 > G41CT3. This could also be correlated with B cell recall responses in which an identical hierarchy was obtained on restimulation of G41CT3-primed B cells in adoptive transfer experiments. Subsequent studies revealed that peptide-mediated modulation of Th cell recruitment by Ag-primed B cells was probably due to differences in on-rates for engagement of B cell Ag receptor by these analogues. This was despite the fact that all three peptides displayed equally randomized conformations in solution. These studies indicate that even subtle variations in the flanking sequences can markedly influence the immunogenicity of B cell epitopes.
Amino Acid Sequence↗
An NADH-dependent disulfide reductase activity in the endoplasmic reticulum of Dictyostelium discoideum.
A novel disulfide reductase activity was observed in the amoeba, Dictyostelium discoideum. Both 5,5'-dithiobis(2-nitro-benzoate) (DTNB) and insulin were substrates for reduction. NADH was utilized in preference to NADPH. The activity comigrated with NADPH-dependent cytochrome c reductase on sucrose gradients, suggesting localization in the endoplasmic reticulum (ER). The buoyant density of the disulfide reductase was not shifted when ribosomes were released from the ER nor was the activity solubilized when membranes were shocked with low osmotic buffer. It therefore appears that the reductase was membrane-bound in the lumen of the smooth ER.
Animals↗
Biochemical and molecular characterization of a manganese peroxidase isoenzyme from Pleurotus ostreatus.
In this study we purified and investigated the catalytic properties of a manganese peroxidase isoenzyme produced by the fungus Pleurotus ostreatus in liquid medium with peptone as nitrogen source. The isoenzyme was purified to homogeneity by chromatography on Bio-Rad Q-cartridge, Sephacryl S-200 and Mono-Q with activity yield of 59% and a purification factor of 36. The P. ostreatus MnP obtained had the same pI (3.75) and N-terminal sequence as MnP-1 of Pleurotus eryngii produced in the same medium (both exhibiting Mn-independent activities on phenolic and non-phenolic substrates). However, the N-terminal sequence of this P. ostreatus isoenzyme differed from a previous published sequence of MnP from this fungus. The results obtained show the importance of media composition in the production of different isoenzymes within the same fungal species. We have also demonstrated by Southern blots that the different isoenzymes are probably encoded by different genes, and that the MnP genes in both Pleurotus species are similar but different to those of Phanerochaete chrysosporium.
Blotting, Southern↗
Regulation of beta- and gamma-actin mRNA by thyroid hormone in the developing rat brain.
The relative sensitivity of the two isotypes of actin mRNA (beta and gamma) to thyroid hormone (T3) was examined by comparing the steady state levels of these mRNAs with their rates of transcription in cerebra from normal and hypothyroid rats of different ages, covering the period of synaptogenesis (days 1-20 postnatal). Hypothyroidism was associated with a reduction in the steady state level of beta-actin mRNA during the entire period, but levels of gamma-actin mRNA were reduced only during the early phase of synaptogenesis (first week). The rats of transcription of both beta- and gamma-actin mRNAs were stimulated by T3 during the early phase but that of beta-actin mRNAs was relatively more sensitive to T3 than gamma-actin mRNA. The lack of correlation between the rates of transcription of beta- and gamma-actin mRNA at different ages with their corresponding steady-state levels suggests additional post-transcriptional regulation.
Actins↗
Integration of high-risk human papillomavirus DNA is linked to the down-regulation of class I human leukocyte antigens by steroid hormones in cervical tumor cells.
A crucial event in the malignant progression of cervical intraepithelial neoplasia appears to be the up-regulation of high-risk human papillomavirus (HPV) early gene expression. Steroid hormones have been linked to the progression from premalignant to neoplastic status in HPV positive lesions. This report demonstrates that at physiological levels, the glucocorticoid hormone hydrocortisone consistently down-regulates class I human leukocyte antigen (HLA) surface expression in HPV-positive cervical tumor cells but can up-regulate expression in HPV-negative epithelial tumor lines. Suppression of HLA expression was also seen with progesterone, another steroid hormone. The hydrocortisone-mediated modulation of HLA expression is dependent on integration and transcription of the HPV genome and can be blocked by Ru38486, an antagonist of both glucocorticoid and progesterone receptors, indicating the role of these receptors in mediating HLA suppression. The data suggest that HPV integration events in cervical epithelia correlate with hormone-dependent HLA suppression, possibly contributing to the avoidance of tumor recognition by cytotoxic T cells. These studies imply that clinical use of steroids may be contraindicated in HPV-positive individuals who have early premalignant cervical disease or neoplasia but provide evidence that the antiprogestin Ru38486 may be useful in the management of early stage cervical disease.
Carcinoma↗
The plasma-membrane Ca2+-ATPase of Leishmania donovani is an extrusion pump for Ca2+.
Controlled exposure of Leishmania donovani promastigotes to hypotonic shock results in the formation of deflagellated unsealed ghosts of original polarity that largely retain the pellicular microtubular structure associated with plasma membrane of the parasite. Gentle shearing followed by suspension of the purified membrane in appropriate isotonic buffer containing Mg2+ (4mM) results in the formation of sealed everted vesicles. The presence of Mg2+ (4 mM) appears to be essential for efficient sealing and also to prevent leakiness. ATP-dependent Ca2+ accumulation can be demonstrated in these vesicles Km values for Ca2+ and ATP were 125 nM and 0.8 mM respectively. The accumulated Ca2+ reaches a concentration of 1.1 mM. Ca2+ uptake is completely inhibited by vanadate (40 microM) and several thiol-modifying agents. Using 5,5'-dithiobis-(2-nitrobenzoic acid) as the modifying agent, an excellent correlation between loss of enzyme activity and transport capability and their parallel regeneration in the presence of 2 mM dithiothreitol was demonstrated. Using 2'.7-bis(carboxyethyl)-5(6)-carboxyfluorescein as the fluorescent pH probe, it was observed that Ca2+ entry into the vesicles is accompanied by an outward movement of H+ from the vesicles. Taken together, this paper establishes that the high-affinity transmembrane Ca2+-ATPase [Ghosh, Ray, Sarkar and Bhaduri (1990) J. Biol. Chem. 265, 11345-11351; Majumdar, Mukherjee, Ray and Bhaduri (1992) J. Biol. Chem. 267, 18440-18446] is an extrusion pump for Ca2+ in this human pathogen.
Adenosine Triphosphate↗
Pneumocystis carinii pneumonia masquerading as tuberculosis.
Recent laboratory studies indicate that genetic diversity exists in human strains of Pneumocystis carinii. Structural and functional variability in infecting strains could result in differences in host-parasite interactions and the natural history of P carinii pneumonia. We report 5 unusual cases in which the clinical presentation mimicked tuberculosis. All patients were cared for at a university-based public hospital clinic in Los Angeles, Calif, during a 2-year period. These patients were chronically ill, had lost weight, and each had cavities or cystic spaces as the primary radiographic findings. None were receiving aerosol pentamidine and only one had a history of smoking. Four patients were initially treated for tuberculosis and the fifth for disseminated Mycobacterium avium complex. Pneumocystis carinii was the only pathogen identified in each case. The unusual clinical presentations delayed the diagnosis of P carinii in all 5 cases. Practitioners must be aware of the variable presentations of P carinii pneumonia.
Adult↗