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Biomedical subjects

S Mukherjee

Publications and source records attributed to S Mukherjee.

At least 199 records · Page 11Linked to original sources
PubMed1996

Initial characterization of viral sequences from a SHIV-inoculated pig-tailed macaque that developed AIDS.

In this study, we report on the derivation of a pathogenic SIV-HIV chimeric virus (SHIV) and the initial characterization of the viral sequences from the first (macaque PPc) of a series of pig-tailed macaques that developed CD4+ T cell loss and AIDS. Viral genes were amplified by PCR from the brain, lymphoid, and kidney tissues and their sequences compared to the original SHIV used to initiate passages in macaques. Our results show that the vpu gene, which was nonfunctional in the original SHIV, now coded for functional protein in macaque PPc. The tat and rev genes had no consensus changes but the nef gene had 4-5 consensus changes, depending on the tissue examined. The gp 120 gene had the highest number of nucleotide and amino acid substitution rates that varied from 0.64% to 1.44% and 1.17% to 3.71%, respectively, again depending on the tissue examined. These results suggest that a constellation of changes accumulated at the genomic level during the derivation of a SHIV that was pathogenic for pig-tailed macaques.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Termination of pregnancy in rodents by oral administration of praneem, a purified neem seed extract.

PROBLEM: Development of an orally administered abortifacient. METHODS: Subjects were female Wistar rats, weighing 150 to 200 g at the time of experiments. Praneem (a purified extract of neem Azadirachta indica) at a dose of 0.6 ml was given orally from day 8 to 10 after confirming presence and number of implants surgically on day 7 of pregnancy. The animals were examined again under anesthesia on day 15 of pregnancy to check the number of developing embryos. Controls received an equivalent regime of peanut oil. The number and size of implants were counted five days after treatment. RESULTS: Complete resorption of embryos was observed on day 15 of pregnancy in every animal treated with Praneem in contrast to normally developing embryos in rats given peanut oil. In repeat batch experiments, it was established that the effect of the treatment was reversible and animals regained fertility in cycles subsequent to treatment with Praneem. Cytokines of Th1 type, i.e., gamma interferon and TNF, were raised on administration of Praneem, which may be the probable cause of pregnancy termination. CONCLUSIONS: Praneem on oral administration can cause termination of pregnancy in rodents, and the action is probably mediated by TH1 cytokines.

Abortifacient Agents, Nonsteroidal↗
PubMed1996

Cortical blood flow and negative symptoms in schizophrenia.

An association between negative symptoms and frontal cortex abnormalities has been suggested in schizophrenic patients. We tested whether this association can be found when patients' task performance is good and while controlling for possible cortical atrophy. We investigated regional cerebral blood flow with the xenon-133 inhalation method in 9 unmedicated schizophrenic patients at rest and during performance of the Continuous Performance Test. Negative symptoms were quantified with the Scale for Assessment of Negative Symptoms. All patients could attend to the test and performed it successfully with mean accuracy of 91 +/- 8%. Changes of the left hemisphere hyperfrontality ratio were significantly correlated with severity of negative symptoms, especially for the subscales of attention (r = -0.83) and anhedonia (r = -0.70). These results lend further support to the putative association between negative symptoms and physiological abnormalities of the frontal cortex in schizophrenic patients.

Adult↗
PubMed1996

Experimental Evaluation of a New Single Wire Stainless Steel Fishscale Coronary Stent (Freedomª).

Recent randomized clinical trials revealed a significant reduction in angiographic restenosis rates when adjunctive stenting was performed after conventional coronary balloon angioplasty. Current approved coronary stents are however hampered by their rigidity, limiting their trackability in tortuous vessels and furthermore, needing high pressure deployment for optimal vessel apposition. New coronary stents are currently under development, using more biocompatible metal alloys and/or designs which better align to the vessel wall at moderate deployment pressures. We evaluated the safety, efficacy, angiographic and histological effect of a new stainless steel fishscale designed stent (Freedomª, Global Therapeutics, Co., USA) in a porcine coronary and peripheral artery model. Implantation in the right coronary artery was successful in all 20 pigs. Control angiograms at 6 weeks follow-up demonstrated patent vessels and morphologic evaluation showed only a mild fibromuscular neointimal response resulting in an area stenosis of 28.7 +/- 0.18% and a mean neointimal hyperplasia of 0.18 +/- 0.25 mm. Comparison with the Palmaz-Schatzª coronary stent in a porcine peripheral artery model demonstrated similar quantitative angiographic and morphologic vessel analysis results. Also the morphometric data were comparable. Area stenosis: Palmaz-Schatz: 37 +/- 0.24%, Freedom: 21 +/- 0.14%, p = 0.07. Mean neointimal hyperplasia: Palmaz-Schatz: 0.33 +/- 0.24 mm, Freedom: 0.18 +/- 0.08 mm, p = 0.08. CONCLUSION: Freedom coronary stent implantation in a porcine model resulted in a high procedural success without subacute thrombotic occlusions, despite no further anticoagulation nor antiplatelet therapy. Six weeks histopathological and morphometric evaluation demonstrated only a mild fibromuscular neointimal hyperplasia.

Journal Article↗
PubMed1996

Kinetics of entry of virulent and avirulent strains of Leishmania donovani into macrophages: a possible role of virulence molecules (gp63 and LPG).

Specific receptors may be involved in the process of attachment of Leishmania donovani promastigotes to macrophage surfaces and their subsequent internalization. Two virulent strains of Indian L. donovani (AG83 and GE-I) were found to enter into macrophages much faster than the avirulent ones (UR6). These virulent promastigotes express surface glycoprotein (gp63) and lipophosphoglycan (LPG) to a greater extent than avirulent strains. We examined their interaction with macrophages as a function of time by preblocking the macrophage receptors with the exogenous addition of gp33 or LPG. In experiments where gp63 was used as the blocking agent, the entry of one virulent strain (GE-I) was affected. In other experiments where LPG was used, the entry of another virulent strain (AG83) was affected. Entry of the avirulent strain (UR6) was unaffected by either of these treatments. Exposed LPG or gp63 on the surface of promastigotes thus appear to expedite their recognition and entry into the host cell. To assess the role of gp63 further in the entry of Leishmania into the macrophages, an avirulent UR6 strain was transfected with the gp63 gene cloned from L. amazonensis. The transfected UR6 as expected expressed more GP63 at a faster rate and entered into the macrophages like the virulent strain when compared to the nontransfected UR6 or UR6 transfected with vector alone. Thus, the expression of the gp63 gene is involved in the recognition and intracellular entry of visceral Leishmania into the macrophages in addition to the cutaneous species demonstrated previously.

Animals↗
PubMed1996

Infections in the immunocompromised host: a prospective multicenter survey in patients receiving chemotherapy for acute leukemia.

Patients receiving chemotherapy for acute leukemia were prospectively followed up to determine the frequency, nature and outcome, of episodes of infection during a 6 or 12 month period at each of the participating centres. A total of 605 cycles of chemotherapy were surveyed. Of these, 490 cycles were received by patients with acute lymphoblastic leukemia (ALL) and 115 by patients with acute non-lymphoblastic leukemia (ANLL). 241 episodes of infection were recorded during the survey: 179 among ALL patients and 62 among patients of ANLL. Infections were more common during chemotherapy for ANLL than for ALL, occurring in 54% (62/115) and 36% (179/490) of chemotherapeutic cycle respectively. A favorable response to empiric antibacterial agents was seen in 39% (23/59) of episodes in ANLL patients and 77% (134/174) of episodes among ALL patients. Infection presented as fever of unidentified origin in an overwhelming majority (63%) of episodes. Gastroenteritis and pneumonia occurred with a frequency of 11% and 10% while the frequency of all other diagnoses was 3% or less. Overall, E coli and Candida were the most frequently isolated organisms while Staphylococcus aureus and Group A Streptococci were the most frequent isolates from blood and throat swabs, respectively. A high degree of resistance to commonly used antimicrobial agents was seen among the most frequently isolated organisms. About 75% of episodes of infection which did not respond to antibacterial agents responded to empiric systemic antifungal therapy; although fungi were mycologically isolated in only a quarter of these instances. Oropharyngeal candidiasis occurred in association with 3% of chemotherapeutic cycles.

Humans↗
PubMed1995

Interaction of virion protein Vpr of human immunodeficiency virus type 1 with cellular transcription factor Sp1 and trans-activation of viral long terminal repeat.

Acquired immunodeficiency syndrome (AIDS) is a result of replication of the human immunodeficiency virus type 1 (HIV-1) predominantly in CD4+ T lymphocytes and macrophages. However, most of these cells in vivo are immunologically quiescent, a condition restricting HIV-1 replication. Vpr is an HIV-1 virion protein suspected to enhance HIV-1 replication in vivo. We demonstrate in this report that Vpr specifically activates HIV-1 long terminal repeat (LTR)-directed transcription. This effect is most pronounced on a minimal promoter from HIV-1 LTR containing the TATA box and binding motifs for the ubiquitous cellular transcription factor Sp1. Evidence is presented that Vpr interacts with Sp1 when Sp1 is bound to the Sp1 motifs within the HIV-1 LTR Both Vpr-Sp1 interaction and Vpr trans-activation require a central Leu/Ile-rich domain in Vpr. Our findings suggest that Vpr trans-activation through Sp1 is most critical for the immediate early transcription of HIV-1 when other positive regulators, such as NF-kappa B, are limited or inactive, a condition presumably present in vivo. By interacting with Sp1, Vpr also has the potential to influence cellular gene expression and cellular functions. Thus, therapeutic approaches directed toward blocking the Vpr trans-activation function could prove valuable in treating AIDS.

Base Sequence↗
PubMed1995

Monosialoganglioside cotreatment prevents haloperidol treatment-associated loss of cholinergic enzymes in rat brain.

Effects of monosialoganglioside (GM1 ganglioside) cotreatment with haloperidol (HAL) were studied in rat on the haloperidol treatment-associated changes in cholinergic enzymes, choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) in three brain regions of interest: striatum, hippocampus, and cerebral cortex. Short-term (8 days) haloperidol treatment significantly increased the levels of both ChAT and AChE in all the three regions of brain, as compared with controls (for ChAT: p < .0001 for all comparisons, and for AChE: striatum: p < .0001; hippocampus: p < .0003; cortex: p < .05). Cotreatment with GM1 ganglioside further increased the ChAT activity relative to haloperidol treatment alone in all three regions (p < .05). The AChE activity was also significantly higher than controls in all three regions (p < .05 for all comparisons) and higher than haloperidol treatment only in hippocampus (p < .02). After chronic haloperidol treatment (45 days), ChAT activity in cortex had returned to control values in both HAL and HAL + GM1 groups, with no significant group differences remaining (p = .10). By contrast, relative to control values, HAL and HAL + GM1 groups both showed lower ChAT activity in the striatum, as well as in the hippocampus (p < .0001 for both), with significantly lower ChAT activity in the HAL than in the HAL + GM1 group for both areas (p = < .0001 for both). AChE activity showed a significant difference only between the HAL and HAL + GM1 groups in the cortex (p = .003), but no significant effects of group were seen on AChE activity in either striatum or hippocampus. These data suggest that the protective effects of GM1 ganglioside cotreatment on haloperidol-induced alterations in cholinergic systems can be relevant for protecting against the complications of neuroleptic-induced parkinsonism.

Animals↗
PubMed1995

Regional cerebral blood flow in mood disorders: IV. Comparison of mania and depression.

Cortical regional cerebral blood flow (rCBF) was assessed in minimally medicated, relatively young adults in episodes of either acute mania (n = 11) or major depression (n = 11) and in matched normal control subjects (n = 11), using the 133xenon inhalation method, under eyes-closed, resting conditions. The three groups were equivalent in global CBF. Both patient groups showed significant reductions of rCBF in anterior cortical areas and reduction of the normal anteroposterior gradient. In addition, there was evidence of abnormal, albeit similar, patterns of flow lateralization on a regional basis in both clinical groups compared with normal subjects. An exploratory analysis revealed preliminary evidence of rCBF differences between the clinical groups, localized to the inferior frontal cortex. Otherwise, the evidence in this study suggests that young adult manic and depressed patients are predominantly similar in cortical rCBF parameters.

Administration, Inhalation↗
PubMed1995

Characterization of two proteinase inhibitor (ATI) cDNAs from alfalfa leaves (Medicago sativa var. Vernema): the expression of ATI genes in response to wounding and soil microorganisms.

cDNAs encoding two Bowman-Birk proteinase inhibitors were isolated from the leaves of alfalfa (Medicago sativa). The cDNAs are derived from a small gene family (3 to 10 genes) encoding alfalfa trypsin inhibitors (ATIs). Each cDNA clone encoded a mature ATI that was part of a larger, putative preprotein. ATI mRNAs are continuously expressed in flower parts, but are mechanically wound-inducible in the stems and leaves. ATI mRNA is shown to be continuously present in roots of soil-grown plants, but its presence is primarily in response to microorganisms present in the soil. Additionally, while mechanical wounding of the alfalfa roots induced ATI mRNA synthesis both in the roots and in the leaves, microbial infection of the roots triggered ATI mRNA synthesis in the roots but not in the leaves. These results suggest that both local and systemic signalling pathways for proteinase inhibitor synthesis are present in alfalfa plants.

Amino Acid Sequence↗
PubMed1995

Partial purification of a phosphoethanolamine methyltransferase from rat brain cytosol.

The conversion of phosphoethanolamine to phosphocholine requires 3 separate N-methyltransferases. We had previously purified the enzyme catalyzing the last methylation, phosphodimethylethanolamine N-methyltransferase. We have successfully purified the enzyme catalyzing the initial methylation of phosphoethanolamine. A 434 fold purified enzyme from rat brain was obtained by the sequential use of ammonium sulfate fractionation, Q-Sepharose fast flow column chromatography and a omega-aminoethyl agarose column chromatography. The pH optimum was 11 or greater, the Km value for phosphoethanolamine was 167.8 +/- 41.7 microM and the Vmax was 487.3 +/- 85 mmoles/mg/hr. The kinetics for S-adenosyl-methionine, the methyldonor, has characteristics of cooperative binding with a Km of 1.805 +/- 0.59 mM and a Vmax of 16.9 +/- 3.6 mumoles/mg/hr. The activity was stimulated 6 fold by 2.5 mM MnCl2 and inhibited by DZA and S-adenosylhomocysteine. These results reinforce the early in vivo observations which had provided suggestive evidence for the existence of a pathway for the methylation of phosphoethanolamine to phosphocholine in rat brain.

Ammonium Sulfate↗
PubMed1995

Mainstream and sidestream cigarette smoke exposure increases retinol in guinea pig lungs.

We have studied in guinea pigs the effects of cigarette smoke exposure on vitamin A (retinol) levels in plasma, lung, lung lavage, and liver. Smoke was generated from 1R3F cigarettes in a smoke exposure instrument designed by University of Kentucky Tobacco and Health Research Institute. Three-week-old male guinea pigs were exposed to mainstream, sidestream, or sham smoke, generated twice daily from three cigarettes for 6 weeks. In addition, some animals were kept as room controls for some time. After 6 weeks of smoke exposure, some animals were allowed to recover for 6 weeks without smoke. After 6 weeks of smoking, the plasma retinol levels were lower in both smoke exposed groups when compared to the values in the sham group. Furthermore, in comparison to the sham group, the mainstream and sidestream smoke exposed groups showed a 7.6- and 8.3-fold increase in the levels of lung retinol, respectively. After the 6-week recovery period, plasma retinol of both smoke-exposed groups reached the control levels. In contrast, withdrawal of smoking did not show such an effect on the lung retinol level in both mainstream or sidestream groups. Electronmicroscopy of the lungs showed deleterious alterations in the morphology of the lungs in both mainstream and sidestream groups. Although the mechanism(s) involved in the elevation of retinol content of the lung due to smoke exposure remains to be elucidated, it is of interest that elevation of retinol content and alteration of lung morphology occurred not only in the mainstream smoke exposed but also in the sidestream group.

Animals↗