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Biomedical subjects

S Ghosh

Publications and source records attributed to S Ghosh.

At least 361 records · Page 20Linked to original sources

The effect of immunization with porins on gut pathophysiological response in rats infected with Salmonella typhimurium.

Attachment of Salmonella typhimurium to epithelial surfaces elicit significant alterations in different cell signalling events which lead to the development of disease. The present investigation was conducted to evaluate the effect of immunization of rats with porins, on gut physiologic markers following challenge with S. typhimurium. Male albino Wistar rats were immunized with purified porins and challenged by intragastric infection with S. typhimurium. Electrolyte transport, levels of different second messengers and inflammatory mediators were studied. A net absorption of transepithelial fluxes of Na+ and Cl- in immunized-challenged group and secretion in infected group was found. Ca2+ and 3-O-methyl-D-glucose fluxes did not show any change. Significant increase in the levels of [Ca2+]i, cAMP, membrane form of protein kinase C, prostaglandins, NADPH oxidase, Glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, total oxygen free radicals, reactive nitrogen intermediates, citrulline and lipid peroxidation was found in the infected group. However, in the immunized-challenged group, the values of all the parameters were found to be almost the same as that of control as well as immunized groups. Na+, K+-ATPase and calmodulin levels were unaltered in all the groups of animals. The results of this study thus suggest that immunization of rats with purified Salmonella porins followed by subsequent challenge with the organism might be helpful for the prevention of multiple physiologic derangements in isolated ileal cells.

Animals↗

Establishment of synchronization in carrot cell suspension culture and studies on stage specific activation of glyoxalase I.

The present report summarizes and compares the effects of three cell cycle inhibitors, viz. aphidicolin, hydroxyurea and mimosine, in inducing synchronization of a rapidly proliferating suspension culture of carrot. These treatments efficiently synchronized the cell cycle as the doubling time of the cell population was roughly equal to the total length of one cell cycle. Protoplasts derived from mimosine treated cell suspension culture were resolved via flow cytometry to get an idea of the temporal organization of the cell cycle events. The biochemical analysis showed a rise in stage specific activity of glyoxalase I, an auxin inducible marker enzyme activated at G2-M. This activity peak could be shifted to an early phase of interphase in response to auxin treatment.

Cell Cycle↗

Presynaptic dopaminergic function in the nucleus accumbens following chronic opiate treatment and precipitated withdrawal.

Naloxone treatment at three days following implantation of pellets containing morphine base increased uptake of tritiated dopamine by the nucleus accumbens but did not alter efflux of tritiated dopamine by the nucleus accumbens or tritiated norepinephrine by the hippocampus. At six days following placement of pellets containing morphine base, withdrawal score was increased after treatment with either saline or naloxone, indicating that animals were undergoing spontaneous opiate withdrawal. Fractional efflux of tritiated dopamine was decreased at this time point following intermittent stimulation with 317 and 1000 microM 4-aminopyridine, for striatal slices obtained from animals pretreated with either saline or naloxone. For the nucleus accumbens at six days after placement of morphine pellets, similar decreases in the efflux of tritiated dopamine were only observed in slices obtained from naloxone treated animals. Fractional dopamine efflux was also diminished after in vitro exposure to rising concentrations of 4-aminopyridine, amphetamine, or cocaine for tissue obtained from the nucleus accumbens, but not for slices from the striatum at six days following morphine pellet implantation. In conclusion, deficits in dopamine efflux by the nucleus accumbens occur at a time when animals are undergoing spontaneous opiate withdrawal at six days following morphine pellet implantation, but do not occur at an earlier time point when withdrawal is precipitated by naloxone treatment. These deficits are apparent for brain slices obtained from the striatum or nucleus accumbens after exposure to rising concentrations of different in vitro treatments, with tissue obtained from the nucleus accumbens being more sensitive than the striatum to dopamine efflux produced by a wider range of treatments.

Animals↗

Laparoscopic management of ectopic pregnancy.

The incidence of ectopic pregnancy has been rising over the last 20 years. The cause is multifactorial. The technical advancement in the field of minimal access surgery has greatly enhanced the possibility of both diagnosing and treating the condition effectively. The management of ectopic pregnancy can be expectant and surgical; the latter can be by open or laparoscopic methods. Laparoscopic surgery is usually performed when the patient is haemodynamically stable, the hCG is <6000 IU/L, the history is suggestive of minimal pelvic adhesions and when the pregnancy is confined within the tube. This procedure is, however, vastly dependent on the experience and expertise of the surgeon and the equipment facilities available. There are various means of treating ectopic pregnancy by laparoscopy. This includes laparoscopic salpingectomy, salpingotomy, and direct injection of cytotoxic agents. This article will present an overview to ascertain the effectiveness of minimal access surgery in managing ectopic pregnancy. There seems little doubt that laparoscopic management should be the first line of treatment. The way to realize its full potential is by formulating clear guidelines regarding the indication and implementation of laparoscopic surgery and emphasising the role of a fully structured training program to achieve the goals.

Female↗

The role of oxidized HDL in monocyte/macrophage functions in the pathogenesis of atherosclerosis in Rhesus monkeys.

The effect of oxidative modification of high-density lipoprotein (HDL) was assessed by incubation of normal HDL (obtained from Rhesus monkeys fed a stock diet) with 5 microM CuSO4 at 37 degrees C for 12 h/24 h. The physicochemical properties of oxidized-HDL (Ox-HDL) were found to be affected in terms of lipid peroxidation, as observed by the increased level of thiobarbituric acid reactive substances (nmol MDA/mg HDL protein). The biological properties of HDL were altered, since a decrease in the efflux of free cholesterol into the medium was found in the presence of Ox-HDL24h compared with normal HDL (N-HDL). The binding, uptake and degradation of 125I-LDL by macrophages increased in the presence of Ox-HDL24h. The activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione-peroxidase) was reduced in monocytes in the presence of Ox-HDL. However, in the presence of N-HDL, the levels of antioxidant enzymes were maintained at a higher level than in the control (in the absence of HDL) monocytes. Furthermore, the number of monocytes adhered to aortic endothelium were found to be increased in the presence of Ox-HDL. These findings suggest that HDL is susceptible to oxidative modification. Since the parameters selected in the present study are involved in the pathogenesis of atherosclerosis, it can be postulated that the in vivo protection of HDL in atherosclerosis can be reversed in the circumstances in which HDL undergoes oxidative modification like low-density lipoprotein (LDL).

Animals↗

Rhinovirus infections in myelosuppressed adult blood and marrow transplant recipients.

Scant data are available on the clinical significance of rhinovirus infections in immunocompromised patients. We reviewed the clinical courses of and outcomes for 22 myelosuppressed adult blood and marrow transplant recipients with rhinovirus infections who were hospitalized at the M.D. Anderson Cancer Center (Houston) from January 1992 to January 1997. In 15 patients (68%), illnesses remained confined to the upper respiratory tract. Seven patients (32%) developed fatal pneumonia. These patients had profound respiratory failure a mean of 12 days (range, 3-21 days) after the onset of symptoms. In six of these seven cases, rhinovirus was isolated before death from a bronchoalveolar lavage fluid specimen and/or an endotracheal aspirate. Five patients underwent autopsies, one of which revealed disseminated aspergillosis and four of which revealed interstitial pneumonitis and/or acute respiratory distress syndrome and no other organisms. In conclusion, rhinovirus infections may be associated with considerable pulmonary-related morbidity and mortality in severely myelosuppressed immunocompromised patients.

Adult↗

Chicken erythroid AE1 anion exchangers associate with the cytoskeleton during recycling to the Golgi.

Chicken erythroid AE1 anion exchangers receive endoglycosidase F (endo F)-sensitive sugar modifications in their initial transit through the secretory pathway. After delivery to the plasma membrane, anion exchangers are internalized and recycled to the Golgi where they acquire additional N-linked modifications that are resistant to endo F. During recycling, some of the anion exchangers become detergent insoluble. The acquisition of detergent insolubility correlates with the association of the anion exchanger with cytoskeletal ankyrin. Reagents that inhibit different steps in the endocytic pathway, including 0.4 M sucrose, ammonium chloride, and brefeldin A, block the acquisition of endo F-resistant sugars and the acquisition of detergent insolubility by newly synthesized anion exchangers. The inhibitory effects of ammonium chloride on anion exchanger processing are rapidly reversible. Furthermore, AE1 anion exchangers become detergent insoluble more rapidly than they acquire endo F-resistant modifications in cells recovering from an ammonium chloride block. This suggests that the cytoskeletal association of the recycling anion exchangers occurs after release from the compartment where they accumulate due to ammonium chloride treatment, and prior to their transit through the Golgi. The recycling pool of newly synthesized anion exchangers is reflected in the steady-state distribution of the polypeptide. In addition to plasma membrane staining, anion exchanger antibodies stain a perinuclear compartment in erythroid cells. This perinuclear AE1-containing compartment is also stained by ankyrin antibodies and partially overlaps the membrane compartment stained by NBD C6-ceramide, a Golgi marker. Detergent extraction of erythroid cells in situ has suggested that a substantial fraction of the perinuclear pool of AE1 is cytoskeletal associated. The demonstration that erythroid anion exchangers interact with elements of the cytoskeleton during recycling to the Golgi suggests the cytoskeleton may be involved in the post-Golgi trafficking of this membrane transporter.

Animals↗

Antigenic and immunogenic properties of totally synthetic peptide-based anti-fertility vaccines.

In this study we describe the results of experiments in which a variety of totally synthetic luteinizing hormone releasing hormone (LHRH) vaccines were assembled and examined for their abilities to elicit antibody responses and induce sterility in mice. It is shown that totally synthetic vaccines consisting of a 15 residue-defined T cell epitope and the 10 residue LHRH epitope not only induced high titers of antibody but also induced sterility. This effect did not appear to correlate with antibody titer, antibody isotype or comparative antibody affinity, but may be related to the length of time for which antibodies are present to exert their influence.

Amino Acid Sequence↗

The spectrum of ischaemic colitis.

OBJECTIVE: Ischaemic colitis is generally considered a disease of the elderly with considerable cardiovascular morbidity. We aimed to determine the effect of age, co-morbidity and clinical presentation on type, severity and anatomy of involvement of ischaemic colitis. Thrombophilic tendencies have been poorly studied and coagulation status was performed in available patients. DESIGN: Retrospective case identification with prospective follow-up. SETTING: University teaching hospital. PARTICIPANTS: Twenty-four patients (16 female, mean age 64 years) with ischaemic colitis. INTERVENTIONS: Blood analysis for clotting tendencies. MAIN OUTCOME MEASURES: Operation rates, death rates and frequency of clotting abnormalities. RESULTS: Five patients (21%) were below the age of 45, and seven of the 24 had died by the time of follow-up. Four had died of ischaemic colitis during the acute episode. The four patients that died of ischaemic colitis had a more extensive and more severe type of disease and presented with worse clinical features. The main predisposing factors were ischaemic heart disease in 12 (50%) and malignancy in five (21%). Six of the 24 cases (25%) had right-sided lesions and this conferred a good prognosis. Shock, peritonism, extensive disease and uncontrolled atrial fibrillation were all poor prognostic factors. Clotting factor abnormalities could be detected in three of nine patients despite a time lapse between assay and episode of ischaemic colitis. CONCLUSIONS: Ischaemic colitis appears to have two patterns of severity. Anatomical distribution is more variable than a developmental explanation of the vascular supply. Clotting abnormalities may be detected in a minority even on retrospective testing.

Acute Disease↗

Dysphagia in oesophageal intramural pseudo-diverticulosis: fibrosis, dysmotility or web?

We describe two cases of oesophageal intramural pseudo-diverticulosis associated with a cervical oesophageal web presenting as intermittent dysphagia. In both cases, disruption of the web endoscopically resulted in lasting relief from symptoms. This observation, together with a review of the literature written during the past 39 years, suggests that oesophageal web formation may be under-reported in this condition and may be more important than either dysmotility or submucosal fibrosis and stricturing in the aetiology of the dysphagia seen in these patients. All patients with a radiological diagnosis of oesophageal intramural pseudo-diverticulosis should have an endoscopic examination which may be both diagnostic and potentially therapeutic.

Aged↗

Immune effector responses to an excretory-secretory product of Giardia lamblia.

The prior immunisation of mice with purified excretory-secretory product (ESP) led to a complete failure of Giardia lamblia colonisation following challenge inoculation of these animals with trophozoites. The prior immunisation of mice with ESP resulted in a significant stimulation of local immunity as evidenced by a significant enhancement of T helper/inducer activity along with a significant increase in immunoglobulin A-bearing cells. Further, the presence of anti-ESP antibodies in the serum of immunised as well as immunised-challenged animals indicated the stimulation of the systemic lymphoid system. This suggests that the ESP is highly immunogenic and it could be one of the major antigens of G. lamblia responsible for protection against the infection.

Animals↗

Purification and characterization of novel toxin produced by Vibrio cholerae O1.

Vibrio cholerae WO7 (serogroup O1) isolated from patients with diarrhea produces an extracellular toxin despite the absence of ctx, zot, and ace genes from its genome. The toxin elongates Chinese hamster ovary cells, produces fluid accumulation in ligated rabbit ileal loops, and agglutinates freshly isolated rabbit erythrocytes. Maximal production of this toxin (WO7 toxin) was seen in AKI medium with the pH adjusted to 8.5 at 37 degrees C under shaking conditions. We purified this toxin to homogeneity by sequential ammonium sulfate precipitation, affinity chromatography using a fetuin-Sepharose CL-4B column, and gel filtration chromatography, which increased the specific activity of the toxin by 1.6 x 10(6)-fold. The toxin is heat labile and sensitive to proteases and has a subunit structure consisting of two subunits with molecular masses of about 58 and 40 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Agglutination of GM1-coated sheep erythrocytes by toxin suggests that GM1 might be the physiologic receptor for WO7 toxin on the enterocytes. An immunodiffusion test between the antiserum raised against the purified WO7 toxin and the purified toxin gave a well-defined precipitation band. In the immunoblot assay, two bands were observed in the 58- and 40-kDa region. At the same time, antiserum against WO7 toxin failed to show any cross-reactivity with cholera toxin or Escherichia coli heat-labile toxin (LT1) in an immunodiffusion test or immunoblot assay. The enterotoxic activity of WO7 toxin could be inhibited by antiserum against purified WO7 toxin. Our results indicate that WO7 toxin is structurally and functionally distinct from other cholera toxins and that the enterotoxic activities expressed by WO7 toxin appear to contribute to the pathogenesis of disease associated with V. cholerae O1 strains.

Amino Acid Sequence↗

Apoptosis induced by infection of primary brain cultures with diverse human immunodeficiency virus type 1 isolates: evidence for a role of the envelope.

Apoptosis of neurons and astrocytes is induced by human immunodeficiency type 1 (HIV-1) infection in vitro and has been demonstrated in brain tissue from patients with AIDS. We analyzed a panel of diverse HIV-1 primary isolates for the ability to replicate and induce neuronal and astrocyte apoptosis in primary human brain cultures. Apoptosis was induced three- to eightfold by infection with the blood-derived HIV-1 isolates 89.6, SG3, and ADA. In contrast, the brain-derived HIV-1 isolates YU2, JRFL, DS-br, RC-br, and KJ-br did not induce significant levels of apoptosis. The ability of HIV-1 isolates to induce apoptosis was independent of their replication capacity. Studies of recombinant chimeras between the SG3 and YU2 viruses showed that replacement of the YU2 Env with the SG3 Env was sufficient to confer the ability to induce apoptosis to the YU2 virus. Replacement of the Env V3 regions alone largely conferred the phenotypes of the parental clones. The SG3 Env used CXCR4 and CCR3 as coreceptors for virus entry, whereas YU2 used CCR5 and CCR3. The V3 regions of SG3 and YU2 conferred the ability to use CXCR4 and CCR5, respectively. In contrast, the 3' region of Env, particularly the C3V4 region, was required in conjunction with the V3 region for efficient use of CCR3. These results provide evidence that Env is a major determinant of neurodegenerative mechanisms associated with HIV-1 infection in vitro and raise the possibility that blood-derived viruses which emerge during the late stages of disease may affect disease progression in the central nervous system.

Animals↗

Hsp60 is targeted to a cryptic mitochondrion-derived organelle ("crypton") in the microaerophilic protozoan parasite Entamoeba histolytica.

Entamoeba histolytica is a microaerophilic protozoan parasite in which neither mitochondria nor mitochondrion-derived organelles have been previously observed. Recently, a segment of an E. histolytica gene was identified that encoded a protein similar to the mitochondrial 60-kDa heat shock protein (Hsp60 or chaperonin 60), which refolds nuclear-encoded proteins after passage through organellar membranes. The possible function and localization of the amebic Hsp60 were explored here. Like Hsp60 of mitochondria, amebic Hsp60 RNA and protein were both strongly induced by incubating parasites at 42 degreesC. 5' and 3' rapid amplifications of cDNA ends were used to obtain the entire E. histolytica hsp60 coding region, which predicted a 536-amino-acid Hsp60. The E. histolytica hsp60 gene protected from heat shock Escherichia coli groEL mutants, demonstrating the chaperonin function of the amebic Hsp60. The E. histolytica Hsp60, which lacked characteristic carboxy-terminal Gly-Met repeats, had a 21-amino-acid amino-terminal, organelle-targeting presequence that was cleaved in vivo. This presequence was necessary to target Hsp60 to one (and occasionally two or three) short, cylindrical organelle(s). In contrast, amebic alcohol dehydrogenase 1 and ferredoxin, which are bacteria-like enzymes, were diffusely distributed throughout the cytosol. We suggest that the Hsp60-associated, mitochondrion-derived organelle identified here be named "crypton," as its structure was previously hidden and its function is still cryptic.

Alcohol Dehydrogenase↗

Effect of antioxidant vitamin E as a protective factor in experimental atherosclerosis in rhesus monkeys.

Atherosclerosis has been known for many years, yet its etiology remains unknown. Hypercholesterolemia is a major risk factor for atherosclerosis. The mechanism by which it triggers endothelial injury is not known. Since the role of the antioxidant vitamin E on experimental atherosclerosis is inconsistent, the present study was undertaken to evaluate platelet lipid peroxidation and the role of vitamin E (alpha-tocopherol) as protective factor in atherosclerosis in rhesus monkeys. A significant decrease in serum cholesterol and serum triglyceride levels was found in the group of animals which were reverted to stock diet along with vitamin E injections after 9 months of atherogenic diet feeding. Decreases in malonyldialdehyde levels and antioxidant enzyme activities were less significant in animals continued on an atherogenic diet feeding along with vitamin E as compared with animals fed a stock diet with vitamin E supplementation. The overall observations in this study suggest that antioxidant status and lipid peroxidation could be partly restored with vitamin E supplementation in experimental atherosclerosis. Damage to endothelial cells destroys their antithrombotic status and leads to fatal thrombosis. alpha-Tocopherol offers the best hope, but the question is how much of it should be administered for the prevention of atherosclerosis.

Animals↗

Familiality of quantitative metabolic traits in Finnish families with non-insulin-dependent diabetes mellitus. Finland-United States Investigation of NIDDM Genetics (FUSION) Study investigators.

Type 2 diabetes mellitus (NIDDM) is a complex disorder encompassing multiple metabolic defects. There exists strong evidence for a genetic component to NIDDM; however, to date there have been few reports of linkage between genetic markers along the genome and NIDDM or NIDDM-related quantitative traits. We sought to determine whether individual quantitative traits which determine glucose tolerance exhibit familiality in Finnish families with at least one NIDDM-affected sibling pair. Tolbutamide-modified frequently sampled intravenous glucose tolerance tests (FSIGT) were performed on unaffected offspring (n = 431) and spouses (n = 154) of affected sibling pairs sampled for the Finland-United States Investigation of NIDDM Genetics (FUSION) study. FSIGT data were analyzed using the Minimal Model to obtain quantitative measures of insulin sensitivity (SI), glucose effectiveness (SG), and insulin secretion assessed as the acute insulin response to glucose (AIR). The disposition index (DI), a measure of insulin resistance-corrected beta-cell function, was also derived as the product of SI and AIR. Variance components analysis was used to determine for each trait, the heritability (h2), the proportion of the total trait variance accounted for by additive genes. After adjustment for age, gender, and body mass index, h2 estimates were: SG: 18 +/- 9%, SI: 28 +/- 8%, AIR: 35 +/- 8%, and DI: 23 +/- 8%. We conclude that there is strong evidence for modest heritability of Minimal-Model-derived NIDDM-related quantitative traits in unaffected spouses and offspring of Finnish affected sibling pairs.

Adult↗