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Biomedical subjects

S Ghosh

Publications and source records attributed to S Ghosh.

At least 667 records · Page 37Linked to original sources
PubMed1993

Crystallization of the major coat protein of PRD1, a bacteriophage with an internal membrane.

The major multimeric coat protein, P3, of the bacterial virus PRD1 has been crystallized by vapor diffusion from polyethylene glycol 4000. The PRD1-P3 crystals belong to the orthorhombic space group P2(1)2(1)2(1) with unit cell dimensions a = 121.6 A, b = 123.2 A, c = 128.6 A and diffract to 3.0 A resolution. Density measurements show that there is one trimer (3 x 43.1 kDa) per asymmetric unit and a high solvent content of 67%. A self-rotation function calculation shows a pronounced peak indicating a non-crystallographic threefold axis. This indicates that the major viral capsomer is a trimer and allows the viral T-number to be postulated.

Bacteriophages↗
PubMed1993

Statistical mechanics of membrane channels.

Voltage-sensitive membrane channels show co-operative behaviour as evident from electrophysiological experiments. A statistical mechanical approach is suggested for a microscopic analysis of the system. A model of the Zimm-Bragg type is developed for a membrane with a large number of channels behaving co-operatively. The model is tested with voltage-dependent conductance data for gap-junction channels in embryonic cells.

Electrophysiology↗
PubMed1993

Sertoli cell cycle: a re-examination of the structural changes during the cycle of the seminiferous epithelium of the rat.

Seminiferous tubules in mammals are composed of cell associations that show a cyclic pattern of renewal and development. The cyclic nature of germ cell development suggests that the cells supporting the spermatogenic process, the Sertoli cells, might also differ structurally during the spermatogenic cycle in terms of the quantity of their constituents. In the present study, cyclic differences in volumes, and surface areas were determined using a sampling technique at the electron microscope level that proportionally samples the Sertoli cell within the seminiferous tubule. Among the many parameters studied, only the surface area of the cell, the volume of lipid, and the volume and surface area of the rough endoplasm reticulum were shown by statistical analysis to vary cyclically. Regarding rough endoplasm reticulum, the volume and surface area of this organelle peaked at mid-cycle and its low was recorded near the end of the cycle, exhibiting an approximate 15-fold difference between extremes. The rough endoplasm reticulum parameters generally correlated with known patterns of protein secretion within the tubule and with the secretion of specific proteins as well as the factors important in controlling protein secretion. Many Sertoli cell structural parameters suggested to be influenced cyclically in the rat in other studies could not be confirmed by the present study. Methodological differences in the present study and past studies are discussed as potential sources of error for these discrepancies.

Animals↗
PubMed1993

Hydrogen-bond patterns of dialkylpyridone iron chelators and their 1:1 formic acid solvates: description, prediction, and role in crystal packing.

The crystal structures (determined from single-crystal X-ray diffraction studies) and hydrogen-bond patterns of three crystalline 1,2-dialkyl-3-hydroxy-4-pyridones and their 1:1 formic acid solvates are elucidated. The primary hydrogen-bond connectivities observed are explained by a model that predicts that the best donor bonds to the best acceptor. Relative hydrogen-bond donating and accepting abilities of the functional groups observed in these compounds are evaluated by a combination of pKas, energy calculations, resonance arguments, and crystallographic evidence. The primary (O--H ... O) hydrogen-bond patterns are described by graph set notation, and brief explanations of the graph set assignments are also included. A total of 17 secondary (C--H ... O) hydrogen bonds are also observed in these six structures. Correlations are drawn between the observed C--H ... O hydrogen bonds and the molecular packing. The possible role of these secondary hydrogen bonds in influencing molecular packing is discussed.

Crystallography, X-Ray↗
PubMed1993

Failure of sister chromatid separation leads to formation of diplochromosomes in colcemid treated PtK1 cells.

The origin of diplochromosomes has been traced in multinucleate rat kangaroo cells (PtK1) obtained after colcemid treatment. In these cells the diplochromosomes were shown to originate from restitution nuclei, indicating that they were formed due to the omission or failure of sister chromatid separation and not due to endoreduplication. In this context the mechanism of sister chromatid separation has been discussed. The independence of this mitotic event from other associated processes, such as chromosome condensation, nuclear envelope breakdown or spindle formation has been stressed.

Animals↗
PubMed1993

Failure of centromere separation leads to formation of diplochromosomes in next mitosis in okadaic acid treated HeLa cells.

High concentrations of okadaic acid, sufficient to inhibit phosphatase 1 and 2A activities, induces formation of diplochromosomes in HeLa cells. It has been shown that this is due to a failure of sister chromatid separation in earlier mitosis in the presence of okadaic acid in the medium and not due to bypassing of mitosis (endoreduplication). Moreover, it has been demonstrated that the sister chromatid adherence does not depend on any under-replicated chromatin segment shared by the sister chromatids which might happen in okadaic acid induced premature mitosis, but due to the failure of the centromeres to separate at metaphase-anaphase transition. The role of phosphatase 1 in sister chromatid separation has been discussed.

Centromere↗
PubMed1993

Differential expression of the cellular retinaldehyde-binding protein in bovine ciliary epithelium.

Differential expression of the cellular retinaldehyde-binding protein (CRALBP), a likely component of the visual cycle, has been observed in the ocular ciliary epithelium, a bilayer of neurepithelial cells involved in the active transport of aqueous humor. Antibody probes raised to bovine ciliary epithelium were used to isolate a cDNA encoding CRALBP from a bovine ciliary epithelium cDNA expression library. Northern analysis of poly A+RNA isolated from three different regions of the neonate ciliary epithelium revealed a three-fold higher level of CRALBP expression in the most anterior portion of the pars plicata region relative to the posterior pars plana region. Western blot analysis using CRALBP-specific antibodies also demonstrated that the level of CRALBP expression was higher in the most anterior portion of the ciliary epithelium and gradually decreases toward the posterior region in both neonate and adult bovine eyes. Using indirect immunofluorescence and frozen-sectioned bovine ciliary epithelium, CRALBP was localized to the pigmented ciliary epithelial cell layer along the entire ciliary epithelium. In the nonpigmented ciliary epithelial cell layer, CRALBP was only detected in the pars plana region. Pigmented ciliary epithelial cells have also been cultured and CRALBP expression demonstrated for several continuous passages by Northern and Western analysis. These results raise questions regarding the physiological role of CRALBP in the ciliary epithelium and the involvement of the protein in the defining regional and functional boundaries with this tissue.

Animals↗
PubMed1993

Swine as a model of skin inflammation. Phospholipase A2-induced inflammation.

A predictive animal model of skin inflammation is needed for the development of potential therapeutic agents. The existing models of inflammation rely on animals whose skin physiology or biochemistry differs significantly from human. The objective of this investigation was to evaluate the swine as a potential model of inflammation, because its skin has been recognized to exhibit morphologic and functional similarities to human skin. In the swine, an inflammatory response was produced following intradermal injection of snake venom phospholipase A2 (PLA2). This response was characterized by transient erythema (2-3 h) and microscopic changes of cell infiltration, epidermal hyperplasia, and dermal damage, which were apparent two days after PLA2 and peaked by day 7. In general, these microscopic changes persisted up to 21 days. Treatment with the antiinflammatory steroid, betamethasone dipropionate (Diprolene), gave a significant reduction of the inflammatory responses. Heat-inactivated PLA2, ovalbumin, or saline did not provoke this reaction, although PLA2 inactivated by bromophenacyl bromide alkylation did produce an inflammatory response. The alkylated PLA2 was also able to provoke an inflammatory response in the mouse paw edema assay. These results demonstrate that PLA2 can stimulate an inflammatory response in the swine skin, but that phospholipid hydrolytic activity is not required.

Administration, Topical↗
PubMed1993

Higher environmental temperature-induced increase in body temperature: involvement of serotonin in GABA mediated interaction of opioidergic system.

Exposure (2 h) of adult male albino rats to higher environmental temperature (HET, 40 degrees C) significantly increased body temperature (BT). Administration of (a) 5-HTP (5 mg/kg, i.p.) or morphine (1 mg/kg, i.p.) or physostigmine (0.2 mg/kg, i.p.) alone significantly increased and (b) methysergide (1 mg/kg, i.p.) or naloxone (1 mg/kg, i.p.) or atropine (5 mg/kg, i.p.) reduced the BT of both normal and HET exposed rats. Further, it was observed that morphine prevented the methysergide-induced hypothermia and 5-HTP potentiated the morphine-induced hyperthermia in both normal and HET exposed conditions. Biochemical study also indicates that serotonin metabolism was increased but GABA utilization was reduced following exposure to HET.5-HTP or bicuculline-induced hyperthermia in control and HET exposed rat was potentiated with the coadministration of bicuculline and 5-HTP. The cotreatment of bicuculline with methysergide prevented the methysergide-induced attenuation of BT of heat exposed rat, rather BT was significantly enhanced indicating that inhibition of GABA system under heat exposed condition may activate the serotonergic activity. Further (a) enhancement of (i) morphine-induced hyperthermia with physostigmine (ii) physostigmine- or morphine+physostigmine-induced increase of BT with 5-HTP and (b) reduction of (i) morphine- or morphine + 5-HTP-induced hyperthermia with atropine and (ii) atropine-induced hypothermia with 5-HTP in both normal and HET exposed conditions suggest that HET exposure activates the cholinergic system through the activation of opioidergic and serotonergic system and hence increased the BT. Thus, it may be concluded that there is an involvement of serotonergic regulation in the opioidergic-cholinergic interaction via GABA system in HET-induced increase in BT.

5-Hydroxytryptophan↗
PubMed1993

Distribution kinetics of inorganic mercury in the subcellular fractions of fish liver.

The present study tries to find out the kinetics of distribution of mercury in the different subcellular fractions of the liver in a freshwater perch Anabas testudineus over a period of 48 h after a single i.m. injection of [203Hg]mercuric nitrate at a dose of 4 mg/kg body weight. The fish were killed at 15 min, 2 h, 6 h and 48 h post injection. In addition the interaction of this metal with different biomolecules, viz., protein, DNA and RNA, was also investigated. Cytosol was found to be the major site of mercury accumulation. Moderate amounts of accumulation occurred in the nuclear, mitochondrial and microsomal fractions, although varying with time, while the lysosomal fraction did not reveal any spectacular retention of mercury. A significant increase in the protein content of nuclear, mitochondrial, lysosomal and cytosolic fractions was also noticed at different time periods of mercury injection. In the nuclear, microsomal and cytosolic proteins, mercury binding increased more significantly over time than the mitochondrial and lysosomal proteins. A biphasic binding pattern of mercury was seen in nuclear and mitochondrial DNA and mitochondrial and cytosolic RNA.

Animals↗
PubMed1993

Polygenic control of autoimmune diabetes in nonobese diabetic mice.

Partial exclusion mapping of the nonobese (NOD) diabetic mouse genome has shown linkage of diabetes to at least five different chromosomes. We have now excluded almost all of the genome for the presence of susceptibility genes with fully recessive effects and have obtained evidence of linkage of ten distinct loci to diabetes or the prediabetic lesion, insulitis, indicative of a polygenic mode of inheritance. The relative importance of these loci and their interactions have been assessed using a new application of multiple polychotomous regression methods. A candidate disease gene, interleukin-2 (Il-2), which is closely linked to insulitis and diabetes, is shown to have a different sequence in NOD, including an insertion and a deletion of tandem repeat sequences which encode amino acid repeats in the mature protein.

Amino Acid Sequence↗
PubMed1993

Effect on mortality and reinfarction of adding fruits and vegetables to a prudent diet in the Indian experiment of infarct survival (IEIS).

The effects of antioxidant-rich foods as adjuncts to a prudent diet were compared for 12 weeks in a randomized, single-blind and controlled trial in 204 (group A) and 202 (group B) patients with acute myocardial infarction. There was a significant decrease in cardiac end points in group A compared to group B (37 vs 58, p < 0.01) after 12 weeks. Within intervention group A, those 108 patients with greater adherence to the intervention program showed a greater reduction in cardiac end points (14 vs 58, p < 0.001), and a significant decrease in total mortality (6 vs 28, p < 0.001), including cardiac mortality (6 vs 25, p < 0.01) compared to group B. Underlying these beneficial effects, antioxidant-rich foods caused a significantly smaller rise in lactate dehydrogenase (LDH) cardiac enzyme in group A than in group B (427.8 vs 561.6 IU/dL), indicating that the protective influence of such a diet may be observed within 1 week. The subset of group A patients showing reduction in mortality also had a lesser rise in LDH and greater reduction in blood lipids, blood glucose and blood pressures. Antioxidant-rich foods also caused a significant decrease in blood lipids with a lower decrease in high-density lipoprotein cholesterol in group A than in group B. Assay of serum level of antioxidants and long-term follow-up may confirm our observations.

Adult↗
PubMed1993

Chromosomal changes during the acquisition of resistance to adriamycin in tumorigenic human synovial cells.

Chromosome analysis of tumorigenic human synovial cells at different stages of acquisition of resistance to doxorubicin was undertaken. Exposure of the sensitive cells to adriamycin for 2h induced chromatid aberrations, while exposure to the drug for 6h did not show any mitosis. However, drug resistant cells continued to show high frequency of mitosis even in presence of the drug. High frequency of chromatid exchanges were seen during the process of the development of drug resistance by exposure to increased drug concentration. Double minutes, a characteristic feature of resistant cells appeared only when the drug resistance was established in the cells, which was confirmed by drug sensitivity assay.

Animals↗
PubMed1993

Cloning of the bovine plasma selenium-dependent glutathione peroxidase (GP) cDNA from the ocular ciliary epithelium: expression of the plasma and cellular forms within the mammalian eye.

In the anterior segment of the mammalian eye, the ocular ciliary epithelium produces the aqueous humor, a fluid that nourishes and protects the avascular tissues from oxidative stress. This report details the results of a study of molecular cloning, sequencing, and expression of plasma glutathione peroxidase (GPx-P) from the bovine ocular ciliary epithelium. The bovine GPx-P cDNA contains an open reading frame of 226 amino acids with a calculated molecular weight of 24,860. The corresponding amino acid sequence showed an overall identity of 88% with the human GPx-P, 88.5% with the rat GPx-P, and 46.4% with the cellular bovine glutathione peroxidase (GPx-1). The levels of GPx-P and GPx-1 transcripts in ocular tissues were analyzed and the ciliary epithelium was found to express the highest levels of GPx-P transcripts in human and bovine eyes, whereas the cornea of calf eyes expressed the highest levels of GPx-1 transcripts. Surprisingly, the lens, on which oxidants have profound effects leading to cataract formation, expressed the lowest levels of GPx-P and GPx-1 transcripts in human donor eyes. These results provide new evidence of differential gene expression of the GPx-P and GPx-1 forms in the mammalian eye and stresses the functional role of the ocular ciliary epithelium in protecting the anterior segment of the eye from oxidative damage.

Amino Acid Sequence↗
PubMed1993

Surface and surface-to-volume relationships of the Sertoli cell during the cycle of the seminiferous epithelium in the rat.

The surface relationships of the Sertoli cell and the surface relationships of the Sertoli cell in comparison to the changing volumes of developing germ cells were studied using morphometric techniques at periods representing nine groupings of the fourteen defined periods in the cycle of the seminiferous epithelium of the adult rat. No cyclic variation in the total Sertoli plasma membrane surface area was noted. Cyclic variations were noted in the area of the Sertoli cell surface that faces the basal compartment germ cells, but not the basal lamina. No cyclic variations were noted in the amount of contact of the Sertoli cells with each other at the level of the Sertoli cell barrier. However, when areas in the adluminal compartment were studied, significantly less Sertoli-Sertoli contact was seen in stages V through VII than in other stages with the exception of stages II-IV. Surface contact of germ cells with Sertoli cells increased progressively as germ cells entered the intermediate compartment and progressed to late spermatids. However, a calculation of the surface-to-volume ratio showed that surface increases of the Sertoli cell in relation to the volume of germ cells were greatest in elongating spermatids past step 12 of spermiogenesis. The area in which Sertoli ectoplasmic specializations faced germ cells was determined throughout spermatogenesis, and these data demonstrated that the first appearance of ectoplasmic specialization was at the mid-pachytene phase. They also showed that stage VIII was a period when ectoplasmic specialization loss from the cell surface was evident. Less Sertoli ectoplasmic specialization face step 8 and step 19 spermatids than comparable germ cell types at other stages. In addition to Sertoli cell surface area changes during the cycle, volumes of individual germ cell types were determined for the first time. The data presented allow an objective understanding of the complex structure and relationships of the Sertoli cell and provide a basis for understanding functional changes and interpreting biochemical data.

Animals↗
PubMed1993

A prospective, randomized, blinded, and placebo-controlled trial of intraoperative intra-arterial urokinase infusion during lower extremity revascularization. Regional and systemic effects.

OBJECTIVE: This study was designed to evaluate the safety and regional and systemic effects of three doses of urokinase (UK) infused into the distal arterial circulation during routine operative lower extremity revascularization. METHODS: One hundred thirty-four patients were prospectively randomized to receive one of three bolus doses of UK (125,000, 250,000, or 500,000 U) or placebo (saline) infused into the distal circulation before lower extremity bypass for chronic limb ischemia. Regional (femoral vein) and systemic (arm) blood was sampled before drug infusion, prereperfusion, and postreperfusion, and systemic blood samples were obtained 2 hours postreperfusion. Assays evaluated plasma levels of fibrinogen, fibrin(ogen) degradation products (FDP), fibrin breakdown products (D-dimer and fragment B-beta 15-42), and plasminogen. Patients were monitored for clinically evident bleeding complications. The Wilcoxon rank-sum test was used to compare different drug doses with the placebo. RESULTS: Intraoperative bolus UK infusions produced no significant fibrinogen breakdown compared with placebo. There was a dose-related decline in plasminogen levels, which became significant at a dose of 500,000 U of UK (p < 0.001). There were dose-related increases in plasma FDP, which became significant at dose of 250,000 and 500,000 U (p < or = 0.005), and in plasma D-dimer, which were significant at all UK doses (p < 0.001). The changes in plasma fibrinogen and markers of fibrin breakdown were similar in the regional and systemic circulations. There was no increase in operative blood loss, blood replaced, or wound hematoma formation. There was an unexplained increased mortality in the placebo group (21.1% vs. 2.0%, p = 0.033). CONCLUSIONS: Intraoperative bolus UK infusion is safe, with no significant fibrinogen depletion or increased operative blood loss or wound hematoma formation. Dose-related plasminogen activation resulted in significant breakdown in cross-linked fibrin in the distal circulation. Intraoperative bolus UK infusion may be valuable as an adjunct in patients with chronic occlusive disease who are undergoing revascularization. Detailed randomized studies are indicated to establish clinical efficacy.

Aged↗
PubMed1993

Endotoxin-induced organ injury.

OBJECTIVE: To review the effects of endotoxemia on the major organ systems of the body and discuss potential mechanisms of tissue injury. DESIGN: Appraisal of 60 articles representing a cross section of studies relating to in vivo and in vitro responses to endotoxin. MAIN METHODS: Cell cultures, isolated tissue preparations, animal and human studies. RESULTS: Endotoxemia results in the activation of numerous cellular and hematogenous mediators. These mediators range from prostaglandins, thromboxanes, and leukotrienes, to complement components. Tumor necrosis factor may be responsible for initiating many of the observed responses to endotoxin. Species and tissue specificity are a prominent feature of the response to endotoxin. CONCLUSIONS: No single agent can yet be implicated as the common mediator of endotoxin-induced organ injury. Endotoxin initiates the elaboration of a cascade of secondary mediators that amplify the response to the initial insult. The relative importance of individual agents as mediators of the response to endotoxin varies with the experimental model studied.

Animals↗