Creutzfeldt-Jakob disease: report of a case from West Bengal.
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Biopsy↗
Biomedical subjects
S Mukherjee
Publications and source records attributed to S Mukherjee.
Characterization of a leucine-zipper-like domain in Vpr protein of human immunodeficiency virus type 1.
Human immunodeficiency virus type 1 (HIV-1) replicates productively in vitro in CD4(+)-T cells and/or macrophages. In the host, however, HIV-1 replication may be restricted by the quiescence of susceptible cells. Vpr is a 15-kDa late viral gene product, which is assembled in the virion and suspected to enhance HIV-1 replication in the infected host. We demonstrated previously that Vpr interacted specifically with the cellular transcription factor Sp1, and activated transcription from the HIV-1 long-terminal-repeat. Both Vpr-Sp1 interaction and trans-activation by Vpr required a central Leu/Ile-rich domain (LR domain, aa 60-81) in Vpr. This domain of Vpr was also found critical for Vpr interaction with another cellular protein of 180 kDa. We now provide biochemical evidence that the Vpr LR-domain has a leucine-zipper-like structure. The leucine-zipper structure has been found in a variety of cellular transcription factors, which use the leucine-zipper domain to form a specific dimer before they can bind to DNA through an upstream basic domain. The LR domain of HIV-1 Vpr, when fused to the basic domain of the cellular transcription factor CREB, was capable of supporting specific DNA binding by the CREB basic domain. Point mutational analysis of the Leu/Ile residues in the LR domain suggested that multiple Leu/Ile residues may be involved in maintaining the leucine-zipper-like structure. Mutagenesis in the context of the full-length Vpr also helped identify Leu/Ile residues may be involved in maintaining the leucine-zipper-like structure. Mutagenesis in the context of the full-length Vpr also helped identify Leu/Ile residues critical for Vpr interaction with the cellular 180-kDa protein. These results suggested that the leucine-zipper-like domain may be an important functional determinant for HIV-1 Vpr.
Amino Acid Sequence↗
Acute effects of haloperidol on cerebral cortex blood flow in normal and schizophrenic subjects.
To evaluate the effects of neuroleptic medications on cerebral blood flow (CBF), cortical perfusion was quantified by the 133xenon technique in 8 unmedicated schizophrenics and 9 healthy controls before, and 1 and 3 hours after, administration of haloperidol (5 mg per os). At 3 hours, the normal subjects, but not schizophrenic patients, showed a significant increase in global mean perfusion (17 +/- 13%). Changes in CBF were not associated with plasma haloperidol levels or the presence of extrapyramidal side effects, and remained significant after controlling for pCO2. The lack of change in CBF in schizophrenic patients following acute haloperidol administration may be due to prior neuroleptic exposure, absence of anxiety, or other nonspecific factors, or may reflect a more fundamental feature of underlying pathophysiology in schizophrenia.
Administration, Oral↗
Static and dynamic response of cluster glass in La0.5Sr0.5CoO3.
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Journal Article↗
Plasma membrane phospholipid fatty acid composition of cultured skin fibroblasts from schizophrenic patients: comparison with bipolar patients and normal subjects.
Recent studies have found lower red cell plasma membrane contents and composition of the long chain polyunsaturated essential fatty acid derivatives, particularly arachidonic acid and docosahexaenoic acid, in a subgroup of chronic schizophrenic patients. These fatty acids are particularly enriched in the brain. Red blood cell levels of fatty acids are influenced by diet, medications, and other factors. Cell plasma membrane compositions of arachidonic and docosahexaenoic acids were therefore examined in cultured skin fibroblasts from 12 schizophrenic patients, 8 of whom were drug-naive and in a first episode of psychosis, 6 bipolar patients, and 8 normal control subjects. Docosahexaenoic acid as well as total n-3 essential fatty acid contents were significantly lower in cell lines from schizophrenic patients than in cell lines from bipolar patients and normal subjects, with no difference between the latter two groups. Arachidonic acid levels did not differ across the groups. The essential fatty acid profile observed is consistent with deficient delta-4 desaturase activity in schizophrenic patients.
Adult↗
Prolonged infection in rhesus macaques with simian immunodeficiency virus (SIVmac239) results in animal-specific and rarely tissue-specific selection of nef variants.
We analyzed the sequence of nef genes from different tissues of three rhesus macaques that had been infected with molecularly cloned SIVmac239 for 88 to 92 weeks. Comparison of the predicted amino acid sequences revealed that each macaque had selected out specific amino acid substitutions and that most of this variation (70%) was confined to four regions, amino acids 39 to 75, 90 to 105, 153 to 167, and 191 to 217, comprising 36% of the protein. The nef genes in these animals underwent extensive genetic variation with average nucleotide and amino acid substitution rates varying from 0.86 to 2.84% and 2.47 to 6.27%, respectively, although tissue-specific selection of nef variants occurred in only 1 of 14 tissues examined in this study. Comparison of the rate of nucleotide and amino acid substitutions in the nef genes to those previously reported in the env in the central nervous system (CNS) and lymph node (LN) revealed that the predicted amino acid substitution rates for Nef were much higher than for the gp120 region of env in the CNS and LN tissues for one macaque. In the two other macaques, the predicted amino acid substitution rates were similar between these two proteins in LN tissues, but the amino acid substitution rates in Nef were significantly higher than in the gp120 from the CNS. Comparison of the nucleotide substitutions in the region of overlap between the env and the nef revealed that approximately 83% of the nucleotide substitutions in this area resulted in a Nef amino acid sequence change, 26% of the nucleotide substitutions resulted in a gp41 amino acid change, and 9.5% of nucleotide substitutions resulted in amino acid sequence changes in both proteins, suggesting a preference for the selection of amino acid substitutions in the Nef in these animals. Our results indicate that in animals infected with SIVmac239 for prolonged periods, variation in the nef occurs at rates similar to or exceeding that observed for the env gene.
Amino Acid Sequence↗
Modulation of binding characteristics of peripheral benzodiazepine receptors in vitamin A-deficient guinea pig lung.
Both vitamin A and peripheral benzodiazepine receptors (PBRs) are involved in the control of cell proliferation and differentiation. The objective of this study was to determine whether vitamin A deficiency causes any modulation in the binding characteristics of the PBRs. Forty-five weanling guinea pigs were divided into three groups (control, pair-fed control, and vitamin A-deficient). Vitamin A-deficiency status was achieved after 90 days of feeding. It caused atelectasis, hyperplasia and metaplasia of alveolar epithelium, acute inflammation of the tracheobronchial tree, and a significant increase in the number of alveolar type II cells. In comparison to the control and pair-fed control groups, the lung of vitamin A-deficient animals had 40.6 and 42.8% less PBR density, respectively. There was no significant difference in the equilibrium dissociation constant (KD) of PBRs between the control and the pair-fed control groups, whereas the KD value was 77.7 and 60% higher in the vitamin A-deficient groups than in the control and the pair-fed control groups, respectively. Furthermore, vitamin A-deficiency caused a decrease in the binding capacity of PBRs in both nuclear and mitochondrial fractions. These results may suggest a close functional relationship between vitamin A and PBRs.
Animals↗
Membrane organization at low cholesterol concentrations: a study using 7-nitrobenz-2-oxa-1,3-diazol-4-yl-labeled cholesterol.
Cholesterol is most often found distributed nonrandomly in the plane of the bilayer, giving rise to cholesterol-rich and -poor domains. Many of these domains are thought to be crucial for the maintenance of membrane structure and function. However, such well-characterized domains generally occur in the membranes that contain relatively large amounts of cholesterol. Cholesterol organization in membranes containing very low amounts of cholesterol has not been investigated extensively. Recent evidence from differential-scanning calorimetric studies suggest that cholesterol may not form uniform monodisperse solutions, as assumed earlier, in the membranes even at very low concentrations. Fluorescent cholesterol analogues, when chosen carefully, offer a powerful approach for studying the distribution and organization of cholesterol in membranes at low concentrations. In this paper, we have studied the organization of cholesterol in membranes at very low concentrations (up to 5 mol % of the total lipid) using a fluorescent cholesterol analogue (NBD-cholesterol) which is labeled with the 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) group at the flexible acyl chain, without any alteration in the structural features necessary for proper membrane incorporation. Our results show that NBD-cholesterol exhibits local organization even at very low concentrations. This is consistent with the recently suggested model of cholesterol organization in membranes at low concentrations, involving the formation of transbilayer, tail-to-tail dimers [Harris, J.S., Epps, D. E., Davio, S. R., & Kezdy, F.J. (1995) Biochemistry 34, 3851-3857]. The implications of such local cholesterol organization in membranes that have very low cholesterol content in vivo, such as the endoplasmic reticulum and the inner mitochondrial membrane, open up interesting possibilities.
1,2-Dipalmitoylphosphatidylcholine↗
Oxygen-dependent leishmanicidal activity of stimulated macrophages.
Peritoneal macrophages pretreated with different stimulants were analysed and compared with their respective controls for their ability to kill intracellular pathogenic L. donovani, (MHOM/IN/1983/AG83) an isolate from Indian subcontinent. Stimulation of macrophages by zymosan showed a higher microbicidal activity as compared to that by PMA. A correlation between microbicidal activity of the macrophages and the parameters related to respiratory burst activity such as liberation of O2-, production of H2O2 and consumption of O2 was sought. All the parameters showed a decrease in case of infected macrophages in comparison to those of the non-infected ones. Thus, it is possible that the impairment of macrophage activation by intracellular Leishmania contributes to their survival in the toxic environment of the host.
Animals↗
Distribution of time of first birth in presence of social customs regulating physical separation and coital frequency.
The interval between marriage and the first birth in India, particularly in rural areas, is much longer than what is observed in western countries. In eastern Uttar Pradesh, the mean interval is observed to be even longer, possibly due to traditional customs such as the female partner's visits to her parents in the early years of marriage and the smaller chance of coition because of the observance of rigid intercourse taboos. Thus the models to explain the length of the interval of marriage to first birth proposed by Western demographers, which assume that the period of cohabitation between marriage and first birth is uninterrupted, often do not describe the data satisfactorily when applied to rural India. In this paper a model to describe data on first birth interval is proposed that takes account of the distributions of timing and periods of physical separation and variation in fecundity with effective marriage duration.
Adolescent↗
Purified neem (Azadirachta indica) seed extracts (Praneem) abrogate pregnancy in primates.
The use of neem (Azadirachta indica) seed extracts (Praneem) given orally for abrogation of pregnancy in subhuman primates is described. Oral administration of Praneem was initiated after confirmation of pregnancy using Leydig cell bioassay estimating rising levels of chorionic gonadotropin (CG) in the blood from day 25 onwards of the cycle and continued for six days. Termination of pregnancy was observed with the appearance of blood in the vaginal smears and decline in CG and progesterone. Pregnancy continued in the control animals treated with peanut oil at the same dose. The effect was observed in both baboons and bonnet monkeys. The treatment was well tolerated; blood chemistry and liver function tests had normal values. The animals regained their normal cyclicity in the cycles subsequent to Praneem treatment.
Abortifacient Agents, Nonsteroidal↗
Free radical pathology and antioxidant defense in schizophrenia: a review.
There is increasing evidence that free radical-mediated CNS neuronal dysfunction is involved in the pathophysiology of schizophrenia. Free radicals (oxyradicals, such as superoxide, hydroxyl ions, and nitric oxide) cause cell injury when they are generated in excess or the antioxidant defense is impaired. Both of these processes seem to be affected in schizophrenia. Evidence of excessive oxyradical generation is premised on the assumption that there is increased catecholamine turnover, though there is little direct evidence to support such a view, which is further accentuated by neuroleptic treatment. However, antioxidant enzymes (superoxide dismutase, SOD; glutathione peroxidase, GSHPx; and catalase, CAT) which are constitutively expressed in all tissues, are found to be altered in erythrocytes of schizophrenic patients. Also, possible oxyradical-mediated injury to CNS is suggested by increased lipid peroxidation products in cerebrospinal fluid and plasma, and reduced membrane polyunsaturated fatty acids (PUFAs) in the brain and RBC plasma membranes. The brain is more vulnerable to oxyradical-mediated injury,because its membranes are preferentially enriched in oxyradical sensitive PUFAs, and damaged adult neurons cannot be replaced. In addition to their pathological role, oxyradicals have critical physiological functions in neuronal development, differentiation, and signal transduction, all of which may be altered in some cases of schizophrenia. It may be possible to define cellular injury processes, investigate underlying dynamic regulatory molecular processes, and find ways to prevent these injury processes using peripheral cell models, e.g., red blood cells, lymphocytes and cultured skin fibroblasts. Information on the clinical implications of these processes are valuable for developing new and innovative therapeutic strategies for schizophrenia.
Antioxidants↗
Photophysics of a neurotransmitter: ionization and spectroscopic properties of serotonin.
The neurotransmitter serotonin plays a modulatory role in the regulation of various cognitive and behavioral functions such as sleep, mood, pain, depression, anxiety, and learning by binding to a number of serotonin receptors present upon the cell surface. The spectroscopic properties of serotonin and their modulation with ionization state have been studied. Results show that serotonin fluorescence, as measured by its intensity, emission maximum, and lifetime, is pH dependent. These results are further supported by absorbance changes that show very similar pH dependence. Changes in fluorescence intensity and absorbance as a function of pH are consistent with a pK(a) of 10.4 +/- 0.2. The ligand-binding site for serotonin receptors is believed to be located in one of the transmembrane domains of the receptors. To develop a basis for monitoring the binding of serotonin to its receptors, its fluorescence in nonpolar media has been studied. No significant binding or partitioning of serotonin to membranes under physiological conditions was observed. Serotonin fluorescence in solvents of lower polarity is characterized by an enhancement in intensity and a blue shift in emission maximum, although the solvatochromism is much less pronounced than in tryptophan. In view of the multiple roles played by the serotonergic systems in the central and peripheral nervous systems, these results are relevant to future studies of serotonin and its binding to its receptors.
Hydrogen-Ion Concentration↗
Utilization of precursor essential fatty acids in culture by skin fibroblasts from schizophrenic patients and normal controls.
Based on the lower levels of long-chain polyunsaturated analogs of essential fatty acids (EPUFAs) in plasma membrane phospholipids of red blood cells, brain and cultured skin fibroblasts from schizophrenic patients, a defective utilization (uptake, conversion to EPUFAs and incorporation into membrane phospholipids) of precursor EFAs has been suggested. Utilization of radiolabeled linoleic (LA, 18:2(n-6)) and alpha-linolenic (ALA, 18:3(n-3)) acids was studied in cultured skin fibroblasts from patients with established schizophrenia and at the first episode of psychosis, and normal controls. Uptake and incorporation of both the EFAs were similar in fibroblasts from both groups of patients studied compared with normal controls. However, although the utilization of LA into arachidonic acid (AA, 20:4n-6) was similar in patients and controls, the utilization of eicosapentaenoic acid (EPA, 20:5(n-3)) into docosahexaenoic acid (DHA, 22:6(n-3)) was significantly lower in first-episode psychotic patients (patients, 96.33 +/- 27.16 versus normals, 161.66 +/- 26.33 nmoles per mg total protein; P = < 0.001). This data indicates that the level of delta 6- as well as delta 5-desaturase may be normal. However, the levels of delta 4-desaturase may be lower in fibroblasts from schizophrenic patients even at the first episode of psychosis.
Adult↗
Generation of biologically active anti-Cryptococcus neoformans IgG, IgE and IgA isotype switch variant antibodies by acridine orange mutagenesis.
Administration of MoAbs to Cryptococcus neoformans capsular glucuronoxylomannan (GXM) can alter the course of infection in mouse models. However, the effectiveness of these antibodies appears to depend on isotype and specificity. Comparison of isotype protection efficacy requires families of MoAbs with identical fine specificity and different constant region domain. The generation of such families by hybridoma technology is not always possible because the immune response produces MoAbs of limited classes or subclasses. In these instances isotype switch variants can be isolated in vitro. Unfortunately, standard methods of recovering spontaneous switch variants are often unsuccessful, mainly because of the low frequency of switching. In this study we demonstrate that acridine orange stimulation of an IgG3 anti-C. neoformans-producing hybridoma can be used to recover the entire set of isotype switch variants: IgGl, IgG2b, IgG2a, IgE and IgA. All isotype switch variants bind to GXM; fine specificity mapping, using an 11 amino acid peptide polysaccharide mimetope, revealed conservation of binding site specificity. Furthermore, all isotype switch variants reacted with an anti-idiotopic MoAb. The functional activity of this set of MoAbs was demonstrated by their ability to enhance phagocytosis and antifungal efficacy of human macrophage-like THP-1 cells, with IgG3 being the most effective and IgE being the least effective.
Acridine Orange↗
Age-related analysis of EcoRI generated satellite DNA-containing chromatin of rat liver.
EcoRI digestion of nuclei and their subsequent lysis with EDTA solubilizes 45% and 36% of chromatin DNA from the liver of young (18 +/- 2 weeks) and old (100 +/- 5 weeks) rats, respectively. After hybridization with 185 bp rat satellite I DNA, these soluble fractions are found to be enriched in specific DNA sequences such as satellite DNA. Besides regular repeat pattern, a major portion of the satellite chromatin forms higher order organization. Digestion kinetics confirms condensation of satellite DNA-containing chromatin similar to that of bulk chromatin in old age. Furthermore, densitometric scanning of the slot-blot of soluble chromatin fractions reveals loss of satellite DNA in the old. However, an increase in the linker histone H1 and its subfraction H1zero in the satellite DNA-enriched fraction of chromatin from old rats suggests greater compaction. These results provide the first evidence that the satellite DNA-containing chromatin differs in the liver of young and old rats.
Aging↗
J774 murine macrophage-like cell interactions with Cryptococcus neoformans in the presence and absence of opsonins.
The interaction of Cryptococcus neoformans with the murine macrophage-like cell line J774.16 was studied in the presence and absence of monoclonal antibodies (MAbs) to the capsular polysaccharide glucuronoxylomannan (GXM). In the absence of MAb 2H1 to GXM, coincubation of J774.16 cells with C. neoformans reduced fungal colony-forming units in only 26.6% of 21 independent experiments. In the presence of MAb 2H1, coincubation of J774.16 cells with C. neoformans reduced fungal colony-forming units in > 95% of experiments. Comparison of the relative efficacy of two IgG1 MAbs revealed that the higher affinity MAb was more effective at low concentrations. Antibody-mediated reductions of C. neoformans colony-forming units by J774.16 cells occurred despite inhibition of nitric oxide synthase, addition of reactive oxygen intermediate scavengers, or the use of a superoxide-deficient J774 mutant line.
Animals↗
Deuteron breakup at extreme forward angles: Failure of a pure Coulomb dissociation description.
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Journal Article↗