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Biomedical subjects

S Ghosh

Publications and source records attributed to S Ghosh.

At least 397 records · Page 22Linked to original sources
PubMed1998

A large sample of finnish diabetic sib-pairs reveals no evidence for a non-insulin-dependent diabetes mellitus susceptibility locus at 2qter.

In the first reported positive result from a genome scan for non-insulin-dependent diabetes mellitus (NIDDM), Hanis et al. found significant evidence of linkage for NIDDM on chromosome 2q37 and named the putative disease locus NIDDM1 (Hanis et al. 1996. Nat. Genet. 13:161-166). Their total sample was comprised of 440 Mexican-American affected sib-pairs from 246 sibships. The strongest evidence for linkage was at marker D2S125 and best estimates of lambdas (risk to siblings of probands/population prevalence) using this marker were 1.37 under an additive model and 1.36 under a multiplicative model. We examined this chromosomal region using linkage analysis in a Finnish sample comprised of 709 affected sib-pairs from 472 sibships. We excluded this region in our sample (multipoint logarithm of odds score </= -2) for lambdas >/= 1.37. We discuss possible reasons why linkage to 2q37 was not found and conclude that this region is unlikely to be playing a major role in NIDDM susceptibility in the Finnish Caucasian population.

Aged↗
PubMed1998

Digital video: a tool for correlating neuronal firing patterns with hand motor behavior.

This report describes the use of multimedia technology for simultaneous recording of single unit responses in cerebral cortex, and imaging of hand kinematics as monkeys grasp and manipulate objects. These imaging methods allow direct correlation of full-frame, full-field video images with the actual spike trains recorded with microelectrodes. Our implementation of digital video provides high-resolution snapshots of the hand motor behavior every 33.3 ms, and a precise calibration and display of the synchronously recorded electrophysiological activity digitized at rates up to 44.5 kHz on the same platform. These imaging methods permit non-invasive, non-traumatic monitoring of both trained and spontaneous activity in experimental animals, while providing synchronized digitized records of neuronal spike trains. We also describe software instruments that quantify and analyze the digitized spike trains. One instrument employs user-selectable objective criteria for distinguishing spikes from noise, separates individual action potential waveforms by their amplitude and duration, and compiles time stamps for each spike train. A second instrument constructs rasters and histograms of repeated behavioral trials using the timing of the corresponding video frame for alignment. These analyses reveal functional classes of cortical neurons signaling specific stages of prehension.

Animals↗
PubMed1998

Cdc2-independent induction of premature mitosis by okadaic acid in HeLa cells.

The induction of premature mitosis by okadaic acid (OA) in HeLa cells in S-phase or in G2-phase has been studied using light microscopy, immunofluorescence, and immunochemical techniques. The observations indicate an involvement of a cdc2-independent pathway in these cells. It has been claimed that inhibition of an OA-sensitive phosphatase, possibly of PP1, induces activation of a kinase which is sensitive to staurosporine and Zn2+. This kinase brings about mitosis-specific cytoskeletal rearrangements, chromosome condensation, and nuclear envelope breakdown, inducing a mitosis-like state. However, other mitotic events do not follow. The possibility that this kinase may be a NIMA-like Nek2 kinase is discussed.

CDC2 Protein Kinase↗
PubMed1998

Sustained stress disrupts the performance and acquisition of delayed alternation in rats.

The effects of sustained stress on acquisition and performance of a delayed alternation task were studied in male rats. Rats lived 24 h per day in operant cages where they earned all of their food via lever pressing. During the stress portion of each experiment, one group of rats was able to avoid or escape signaled intermittent footshock (Avoidance/Escape group), a second group (Yoked) did not have control over shock termination, a third group never received shock (Control). Shock trials were presented around-the-clock at approximately 5-min intervals and the stress portion of each study lasted 1 week. We have previously reported that rats tolerate this paradigm well and avoid/escape 99% of the shock trials. Three experiments were conducted. In Experiment 1, rats learned the delayed alternation task prior to stress onset; in Experiment 2, rats were exposed to stress and the alternation task concurrently; in Experiment 3, rats were stressed for 14 days prior to being required to perform the delayed alternation task. In the first experiment, stress decreased both food intake and the accuracy of responding during the first days of stress. In the second experiment (acquisition), stressed rats required more days to reach asymptotic performance on the alternation task. In Experiment 3, rats stressed for 14 days prior to acquisition of the delayed alternation task performed similarly to controls.

Animals↗
PubMed1998

Serum cholesterol and coronary artery disease in populations with low cholesterol levels: the Indian paradox.

OBJECTIVE: To examine the relation between serum cholesterol and coronary artery disease prevalence below the range of cholesterol values generally observed in developed countries. DESIGN AND SETTING: Cross-sectional survey of two randomly selected villages from Moradabad district and 20 randomly selected streets in the city of Moradabad. SUBJECTS AND METHODS: 3575 Indians, aged 25-64 years including 1769 rural (894 men, 875 women) and 1806 urban (904 men, 902 women) subjects. The survey methods were questionnaires, physical examination and electrocardiography. RESULTS: The overall prevalences of coronary artery disease were 9.0% in urban and 3.3% in rural subjects and the prevalences were significantly (P<0.001) higher in men compared to women in both urban (11.0 vs. 6.9%) and rural subjects (3.9 vs. 2.6%). The average serum cholesterol concentrations were 4.91 mmol/l in urban and 4.22 mmol/l in rural subjects without any sex differences. The prevalences of coronary artery disease were significantly higher among subjects with low and high serum cholesterol concentration compared to subjects with very low cholesterol and showed a positive relation with serum cholesterol within the range of serum cholesterol level studied in both rural and urban in both sexes. Among subjects with low serum cholesterol, there was a higher prevalence of coronary risk factors, hypertension, diabetes, obesity and sedentary lifestyle. Serum cholesterol level showed a significant positive relation with low density lipoprotein cholesterol and triglycerides in all the four subgroups. Logistic regression analysis after pooling of data from both rural and urban, with adjustment of age showed that low serum cholesterol level (odds ratio: men 0.96, women 0.91) had a positive strong relation with coronary artery disease and there was no evidence of any threshold. Diabetes mellitus (men 0.73, women 0.74) and sedentary lifestyle (men 0.86, women 0.74) were significant risk factors of coronary disease in both sexes. Hypertension (men 0.82, women 0.64) and smoking (men 0.81, women 0.52) were weakly associated with coronary disease in men but not in women. CONCLUSION: Serum cholesterol level was directly related to prevalence of coronary artery disease even in those with low cholesterol concentration (<5.18 mmol/l). It is possible that some Indian populations may benefit by increased physical activity and decline in serum cholesterol below the range of desired serum cholesterol in developed countries.

Adult↗
PubMed1998

Consequences of intrathymic TCR engagement by partial agonist on selection events and peripheral T cell activation program.

Functions elicited from mature T cells depend on the nature of the Ag. Thus, an agonist induces a larger set of cytokine responses than a partial agonist. Additionally, Ags present in the thymus influence both the selection of TCRs generated by gene rearrangement and the potential functional program of developing thymocytes. This can be approached by analysing the development of T cells in mice expressing the same transgenic TCR (tgTCR) under different conditions of intrathymic selection. H-2Kbm8 was found to act as a partial agonist for CD8+ T cells expressing a tgTCR specific for the H-2Kb alloantigen. Intrathymic exposure to full or to partial agonist affected the development of thymocytes at different stages, consistent with the respective CD8-independent and -dependent characteristic of the tgTCR/Ag interaction. The presence of the partial agonist led to the accumulation of a major population of thymocytes (tgTCR(high) CD4- CD8(low)) originating from TCR engagement at the immature single-positive CD8(low) stage as evidenced by: 1) results from reaggregated thymic organ culture in the presence of H-2(k/bm8) thymic stromal cells; 2) the absence of CD4+ thymocytes, the development of which depends on rearrangements of endogenous TCR alpha genes; and 3) the identification of the CD8(low) thymocytes as cycling cells. Peripheral CD8(low) T cells selected in an H-2(k/bm8) thymus expressed a partial functional program in response to H-2Kb, akin to the response of CD8(high) T cells to a partial agonist. The analysis of the molecular bases for partial reactivity revealed a correlation with inefficient AP-1, but efficient NF-kappaB transactivation.

Animals↗
PubMed1998

The D arm of tRNATyr is necessary and sufficient for import into Leishmania mitochondria in vitro.

Transfer RNAs are selectively imported from the cytoplasm into mitochondria of kinetoplastid protozoa such as Leishmania . The specific structural features of tRNA which determine selectivity are largely unknown. Using an in organello system from Leishmania , the import signals on tRNATyrand on a synthetic transcript which binds to the same receptor, were studied by deletion and reconstruction analyses. In both cases, short oligoribonucleotides (minihelices) containing the sequence UGGYAGAG were imported with high efficiency in the presence of ATP. This motif is present in the D arm of tRNATyr, as well as in the majority of imported Leishmania tRNAs. Deletion of the D arm, or a point mutation in the conserved motif, reduces importability. The import signal coincides with the binding site for the mitochondrial receptor TAB. tRNAGln, which is not imported, forms non-productive, TAB-independent complexes with the mitochondrial surface. However, the observation that the imported:bound ratio of the D arm minihelix is higher than that of the entire molecule suggests that the post-binding translocation step is constrained in terms of size or structural flexibility. Kinetic studies of minihelix import indicate stepwise insertion of the molecule into import channels.

Animals↗
PubMed1998

Piezoelectric response of scleral collagen.

The piezoelectric coefficients (d31) for a number of bovine and human scleral collagen samples were determined as a function of drying time at room temperature. The measured values of d31 decreased with drying time. There were significant differences in the values of the d-coefficient between the human and bovine eyes as well as in the values obtained from different regions of the eye.

Animals↗
PubMed1998

Molecular cloning of the promoter for rat hepatic neutral cholesterol ester hydrolase: evidence for transcriptional regulation by sterols.

Neutral cholesterol ester hydrolase is a key enzyme in regulating hepatic free cholesterol. Using the CEH specific cDNA sequence in the 5'-untranslated region as a primer, we amplified and cloned 1.3 Kb of promoter sequence upstream of the ATG initiation codon. Analysis of the sequence revealed the presence of a consensus GC-box, which can bind the positive transcription factor Sp1, 35 bases upstream from the transcription start site. Transcriptional regulation by agents perturbing cholesterol metabolism was studied in HepG2 cells by transient transfection assays of the promoter activity in deletion constructs linked to the luciferase reporter gene. Three functional sterol response sequences were identified at positions-92, -160, and -280 of the CEH promoter. The sterol response sequence at position -92 was shown to bind SREBP-2. Therefore, the CEH gene is similar to other genes involved in regulation of cholesterol homeostasis, in that it appears to be transcriptionally regulated by sterols.

Animals↗
PubMed1998

Detection of intranucleolar chromatin using an ultrastructural immunolabelling technique.

The intranucleolar chromatin has been detected by feeding HeLa cells with bromodeoxyuridine and then using an immunocytochemical technique for its detection at the ultrastructural level. Labelling was mainly observed on the dense fibrillar component (DFC), which surrounds the fibrillar centres (FC). Labelling could also be seen on the network within the granular component (GC) of the nucleoli. Ring shaped nucleoli with large FCs showed labelling, in addition, on the FCs. Nucleoli from spread preparations of cells treated with hypotonic salt solution for different periods revealed a nucleolonemal network, consisting of units comparable to rDNA transcriptional units in length and associated with tufts of fibrils and granules. Thread-like axes could be detected running through the units and in between two units. Chromatin could also be identified within these units by the immunolabelling technique. The observations strongly indicate that these units are identical with the rDNA transcriptional units. A dynamic nature of the nucleolar chromatin and nucleolar organization has been discussed.

Bromodeoxyuridine↗
PubMed1998

Induction of premature mitosis in S-blocked onion cells.

Onion root-tip cells were blocked at S-phase by treating them with 5-aminouracil (5AU). These cells were then further treated with caffeine/2-aminopurine (Caf/2AP) or a combination of both in the presence of 5AU. These tyrosine kinase inhibitors were able to induce premature mitosis in the S-blocked cells as evident from the breaks and gaps in the metaphase chromosomes and the presence of laggards and fragments in anaphase. Immunofluorescence showed normal spindle formation in these cells. Immunoblotting of cyclin B revealed that the level of cyclin B was slightly higher in the recovered and treated samples than the S-blocked one. The level of p(34)was found to be almost equal in all three samples as expected. We failed to observe any significant difference in the level of p(34)containing phosphorylated tyrosine. Such premature induction of mitosis by the purine derivatives has also been reported in BHK cells. However, those cells failed to progress through mitosis. A comparative analysis indicates that the plant cells and the animal cells, perhaps, follow identical pathway for the initiation of mitosis. The possible causes for differential behaviour in mitotic progression in these cells have been discussed.

2-Aminopurine↗
PubMed1998

Selegiline prevents long-term changes in dopamine efflux and stress immobility during the second and third weeks of abstinence following opiate withdrawal.

Selegiline is an irreversible inhibitor of monoamine oxidase B with trophic and neuroprotective effects. Because of evidence for decreased dopaminergic function during the withdrawal syndromes associated with opiates and other medications with potential for abuse, we investigated effects of treatment with selegiline on in vitro measures of dopamine efflux following opiate withdrawal. Treatment with 2.0 mg/kg/day of selegiline did not modify the severity of opiate withdrawal, as assessed by weight loss over the first 3 days of abstinence. Opiate withdrawal increased immobility in response to a forced warm water swim test performed during the second and third weeks of abstinence following the onset of withdrawal. Brain slices obtained from the nucleus accumbens of opiate-withdrawn animals immediately following swim stress testing displayed diminished efflux of tritiated dopamine after two in vitro exposures to cocaine or amphetamine. Cocaine increases neurotransmitter efflux through blockade of dopamine reuptake, while amphetamine augments efflux by stimulating release of dopamine from intracellular storage vesicles. Although slices from opiate withdrawal subjects showed decreases in efflux after in vitro treatment with these agents, no differences were observed after exposure to 4-aminopyridine, which increases neurotransmitter release by prolonging action potential duration. These findings indicate mechanisms of action that are specific for catecholamine neurotransmitter systems are important for demonstrating long-term changes in dopaminergic function following opiate withdrawal. Selegiline prevented decreases in the efflux of tritiated dopamine in slices obtained from opiate-withdrawn subjects. In addition, selegiline decreased withdrawal-induced immobility during warm water swim testing. In conclusion, treatment with selegiline can prevent long-term changes in stress-induced immobility and deficits in presynaptic dopaminergic function that occur following the opiate withdrawal syndrome.

Animals↗
PubMed1998

Effect of a mu-selective opioid antagonist on CCK-8-induced changes in thermoregulation in the rat.

We examined the effects of I.C.V. injection of CCK-8 alone and in combination with CTAP, a mu-selective antagonist, on brain surface temperature (Tb), oxygen consumption (VO2), and heat exchange (Q) in unrestrained male S-D rats at an ambient temperature of 20 +/- 0.5 degrees C. CCK-8 (300 ng, I.C.V.) produced hyperthermia (deltaTb: 0.86 +/- 0.22 degrees C) lasting for 30-60 min, which was associated with an increase in VO2 (1.42 +/- 0.28 ml/g/h). There was an increase in Q (1.87 +/- 1.2 cal/g/h) beginning 15 min after injection and lasting for 60 min. The CCK-8-induced hyperthermia was attenuated by a postinjection increase in Q. During the 60-120 min postinjection period, VO2 and Q returned to baseline followed by the return of Tb to preinjection levels. CCK-8-induced increases in Tb, Q, and VO2 were blocked by pretreatment with CTAP (0.75 nmol, I.C.V.) 15 min earlier. CTAP alone did not significantly affect deltaTb, deltaVO2, and deltaQ. These results suggest that, within the thermoneutral zone, the thermoregulatory effects of CCK-8 in the rat involve participation of mu-opioid receptors.

Analysis of Variance↗
PubMed1998

Effects of the serotonin agonists 8-OH-DPAT, buspirone, and DOI on water maze performance.

We have previously reported that the serotonin 5-HT1A agonist 8-OH-DPAT and the 5-HT2c agonist TFMPP impair performance on a water maze. In the present report we extended those studies by examining a second 5-HT1A agonist, buspirone, to see whether its effects paralleled those of 8-OH-DPAT, and by testing the effects of the 5-HT2 agonist DOI. Unlike the open pool Morris water maze, the maze used in these experiments has alleys and doorways. The maze can be easily reconfigured to present rats with both previously learned or new maze challenges. Performance is assessed by time to reach the maze exit platform and the number of wrong doorways entered (errors). At doses that did not affect performance in a previously learned maze, the 5-HT1A agonists 8-OH-DPAT (0.1 mg/kg) and buspirone (1 mg/kg) slowed acquisition of a new maze configuration as measured by both swim time to the exit platform and errors committed. A higher dose of buspirone (10 mg/kg) completely blocked acquisition of a novel maze. In contrast. DOI slowed performance as assessed by swim time on both a well-learned maze as well as acquisition of a new maze, but did not affect error rate on either task, suggesting that this 5-HT2 agonist impaired performance by depressing motor activity. These experiments demonstrate that serotonin agonists, especially the 5-HT1A subtype, can impair learning.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Structural and biological characterization of a novel spermicidal vanadium(IV) complex: bis(pi-cyclopentadienyl)-N,N-diethyl dithiocarbamato vanadium(IV) tetrafluoro borate, [VCp2(DeDtc)](BF4).

In a systematic search for vanadocene complexes with sperm immobilizing activity as a new class of contraceptive agents, we identified V(eta 5-C5H5)2((C2H5)2 NCS2)(BF4) (=[VCp2(DeDtc)](BF4)) as the most potent and stable spermicidal compound. Here we report the detailed biologic and physicochemical characterization of this lead spermicidal compound by computer-assisted sperm analysis, electron paramagnetic resonance spectroscopy, electrochemistry, and X-ray crystallography. [VCp2(DeDtc)](BF4) crystallized in the monoclinic space group P2(1)/c, with unit cell dimensions a = 7.0877(4) A, b = 22.2881(14) A, c = 11.8021(7) A, beta = 94.107(1) degree, V = 1859.6(2) A3. The final structure of [VCp2(DeDtc)](BF4) had an R factor of 0.0581 for 3191 independent reflections. The two sulfur atoms of the dithiocarbamate and centroids of the cyclopentadienyl rings in this vanadocene complex with unique contraceptive potential occupy four tetrahedral--like coordination sites about the central metal atom.

Crystallography, X-Ray↗