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Biomedical subjects

S Datta

Publications and source records attributed to S Datta.

At least 37 records · Page 2Linked to original sources
PubMed2002

A novel role of pedunculopontine tegmental kainate receptors: a mechanism of rapid eye movement sleep generation in the rat.

Considerable evidence suggests that pedunculopontine tegmental cholinergic cells are critically involved in normal regulation of rapid eye movement sleep. The major excitatory input to the cholinergic cell compartment of the pedunculopontine tegmentum arises from glutamatergic neurons in the pontine reticular formation. Immunohistochemical studies reveal that both ionotropic and metabotropic receptors are expressed in pedunculopontine tegmental cells. This study aimed to identify the role of endogenous glutamate and its specific receptors in the pedunculopontine tegmentum in the regulation of physiological rapid eye movement sleep. To identify this physiological rapid eye movement sleep-inducing glutamate receptor(s) in the pedunculopontine tegmental cholinergic cell compartment, specific receptors were blocked differentially by local microinjection of selective glutamate receptor antagonists into the pedunculopontine tegmental cholinergic cell compartment while quantifying the effects on rapid eye movement sleep in freely moving chronically instrumented rats. By comparing the alterations in the patterns of rapid eye movement sleep following injections of control vehicle and selective glutamate receptor antagonists, contributions made by each receptor subtype in rapid eye movement sleep were evaluated. The results demonstrate that when kainate receptors were blocked by local microinjection of a kainate receptor selective antagonist, spontaneous rapid eye movement sleep was completely absent for the first 2 h, and for the next 2 h the total percentage of rapid eye movement sleep was significantly less compared to the control values. In contrast, when N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid, groups I, II, and III metabotropic receptors were blocked, total percentages of rapid eye movement sleep did not change compared to the control values. These findings suggest, for the first time, that the activation of kainate receptors within the cholinergic cell compartment of the pedunculopontine tegmentum is a critical step for the regulation of normal rapid eye movement sleep in the freely moving rat. The results also suggest that the different types of glutamate receptors within a small part of the brainstem may be involved in different types of physiological functions.

Acetylcholine↗
PubMed2002

Vitamin D deficiency in pregnant women from a non-European ethnic minority population--an interventional study.

OBJECTIVE: To determine the vitamin D status of pregnant women from non-European ethnic minorities in South Wales. DESIGN: Prospective study. SETTING: Llandough Hospital, Cardiff, South Wales. SAMPLE: One hundred and sixty pregnant women from a non-European ethnic minority population in South Wales. METHODS: Biochemical screening of vitamin D status was carried out at the first antenatal visit. Women found to be deficient in vitamin D were subsequently supplemented and vitamin D status was rechecked at delivery. MAIN OUTCOME MEASURE: Vitamin D status at delivery. RESULTS: Eighty of 160 women had a vitamin D level below 8 ng/mL at their first antenatal visit and were treated with oral vitamin D. Factors that could influence vitamin D status such as religion, fluency in English and dressing habits did not appear to have any effect, although a higher proportion of women who had lived in Britain for longer than three years had subnormal vitamin D levels. In 58 of those checked at delivery, the mean plasma vitamin D level increased from 6 to 11 ng/mL although the mean parathyroid hormone level was unchanged. CONCLUSION: In view of the high incidence of subnormal vitamin D levels in women from ethnic minorities, we recommend biochemical screening of these women in early pregnancy, with subsequent supplementation where indicated.

Africa↗
PubMed2002

Molecular & evolutionary genetics & drug resistance of the gastric pathogen, Helicobacter pylori.

Helicobacter pylori colonizes the gastric mucosa of more than half of all people worldwide and is the major cause of peptic ulcer disease and an early risk factor for gastric cancer, even though most infections are asymptomatic. Infection occurs preferentially in early childhood and once established tends to persist for years or decades. Much of the pathology H. pylori causes probably results from the host response to infection, which is affected by bacterial genotype, human host characteristics and environmental conditions. H. pylori is one of the most genetically diverse of bacterial species, with different genotypes predominating in different parts of the world. In particular, strains from India differ from those of Europe and East Asia in DNA sequence of several diagnostic gene segments. This outcome invites speculation about H. pylori origins and the possibility of Indian-specific genes that might be uncommon in Western strains. Much has been learned from H. pylori genome sequences, along with epidemiological, mutational, molecular and immunologic analyses. Candidate bacterial colonization and virulence genes and host responses are being identified, and the hypotheses being developed are amenable to tests in cell culture and animal models. These research efforts, many of which are collaborative and international, provide insights into mechanisms of establishment and persistence of H. pylori infection and virulence, and should lead to new, far more potent and cost effective anti-Helicobacter therapies or vaccines, and thereby major improvement in human health worldwide.

Drug Resistance, Microbial↗
PubMed2001

Structure of a quinohemoprotein amine dehydrogenase with an uncommon redox cofactor and highly unusual crosslinking.

The crystal structure of the heterotrimeric quinohemoprotein amine dehydrogenase from Paracoccus denitrificans has been determined at 2.05-A resolution. Within an 82-residue subunit is contained an unusual redox cofactor, cysteine tryptophylquinone (CTQ), consisting of an orthoquinone-modified tryptophan side chain covalently linked to a nearby cysteine side chain. The subunit is surrounded on three sides by a 489-residue, four-domain subunit that includes a diheme cytochrome c. Both subunits sit on the surface of a third subunit, a 337-residue seven-bladed beta-propeller that forms part of the enzyme active site. The small catalytic subunit is internally crosslinked by three highly unusual covalent cysteine to aspartic or glutamic acid thioether linkages in addition to the cofactor crossbridge. The catalytic function of the enzyme as well as the biosynthesis of the unusual catalytic subunit is discussed.

Amino Acid Sequence↗
PubMed2001

The effect of stabilizing additives on the structure and hydration of proteins: a study involving tetragonal lysozyme.

In order to elucidate the effect of stabilizing additives on the structure of proteins and the associated ordered water molecules in the hydration shell, the crystal structures of tetragonal lysozyme grown in the presence of sucrose, sorbitol and trehalose have been refined. Also refined are the structures of orthorhombic and monoclinic lysozyme grown under the conditions in which tetragonal lysozyme is normally grown. A comparison of the two sets of structures with the structure of native tetragonal lysozyme shows that the effect of the additives on the structure of the protein molecule is less than that of the normal minor changes associated with differences in molecular packing. Surprisingly, the same is true of the effect on the hydration shell, represented by the ordered water molecules attached to the protein. Thus, it appears that the cause of the stabilizing effect of the additives needs to be sought outside the immediate neighbourhood of the protein molecule. Sorbitol and trehalose do not coherently interact with the protein. One sucrose molecule binds at the active-site cleft of the enzyme.

Animals↗
PubMed2001

Excitation of the pedunculopontine tegmental NMDA receptors induces wakefulness and cortical activation in the rat.

Microinjection of the excitatory amino acid, L-glutamate into the brainstem pedunculo pontine tegmentum (PPT) has been shown to induce wakefulness, however, it has been unclear that receptors mediate this effect. The aim of this study was to test the hypothesis that in the PPT, L-glutamate induces cortical activation and wakefulness via activation of NMDA receptors. To test this hypothesis, three sets of micro-injections into the PPT were carried out on two different groups of rats that were then allowed to move freely although chronic instrumentation recorded sleep/wake states. Three days after the initial control injections of saline, in a contra-lateral site, Group I was micro-injected with saline + glutamate (saline first, and glutamate 15 min later); after another 3 days, the same rats were micro-injected with the NMDA-receptor-specific antagonist, 2-amino-5-phosphonopentanoic acid, (AP5) + glutamate. Group II received the same initial control injections (saline only), then AP5 + glutamate and the saline + glutamate micro-injections last. In rats that were not pretreated with AP5, microinjection of a 90 ng dose of L-glutamate (0.48 nmol in a volume of 0.1 microl vehicle) kept animals awake for 2-3 hr by eliminating both slow-wave sleep (SWS) and rapid eye movement (REM) sleep. These behavioral state changes were accompanied by concomitant increase in the power of gamma (gamma) frequency (20-60 Hz) waves in the cortical EEG. Pretreatment of L-glutamate injection sites with 0.48 nmol of AP5 blocked L-glutamate-induced-wakefulness and preserved a normal amount of wakefulness and sleep. Pretreatment with AP5 decreased the power of gamma-wave activity below its control level. These results support the hypothesis that the glutamate-induced-wakefulness and cortical activation effects are mediated via the NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed2001

Analysis of dynamic cohort data.

Left-truncated and interval-censored data, termed dynamic cohort data, arise in longitudinal studies with rolling admissions and only occasional follow-up. The authors compared four approaches for analyzing such data: a constant hazard model; maximum likelihood estimation with flexible parametric models; the midpoint method, in which the midpoint of the last negative and first positive test result is used in a Cox proportional hazards model that accounts for left truncation; and a semiparametric method that uses imputed failure times in the Cox model. By using a simulation study, they assessed the performance of these approaches under conditions that can arise in observational studies: changes in disease incidence and changes in the underlying population. The simulation results indicated that the constant hazard model and midpoint method were inadequate and that the flexible parametric model was useful when enough parameters were used in modeling the baseline hazard. The semiparametric method ensured correct parameter (odds ratio) estimation when the baseline hazard was misspecified, but the trade-off increased computational complexity. In this paper, a study of the incidence of human immunodeficiency virus in patients repeatedly tested for the virus at a sexually transmitted disease clinic in New Orleans, Louisiana, illustrates the methods used.

Cohort Studies↗
PubMed2001

Induction of Tax i expression in MT-4 cells by 5-azacytidine leads to protein binding in the HTLV-1 LTR in vivo.

The Tax I trans-activator protein of the human T-cell leukemia virus I (HTLV-I) enhances viral gene expression through enhancer sequences in the viral LTR. These sequences consist of three imperfect 21-bp repeats (TRE-1) and a region between the promoter central and promoter proximal TRE-1 (known as TRE-2). We have previously described the in vivo footprint of the HTLV-I TRE-1s and TRE-2 in two HTLV-I-infected cell lines, MT-2 and MT-4. MT-2 is a high-level producer of virus and shows significant DNA-protein interactions within the TRE-1s and TRE-2. In contrast, the proviral DNA in MT-4 cells is heavily methylated and produces no detectable virus. In this report, we describe the footprints of the TRE-1s and TRE-2 in MT-4 cells that were induced to express high levels of viral proteins by treatment with 5-azacytidine, a potent inhibitor of methylation. The footprints of the TRE-1s in 5-azacytidine-treated MT-4 cells were virtually identical to those observed in MT-2 cells. In contrast, the footprints within the TRE-2 region of 5-azacytidine-treated MT-4 cells did not resemble those in either MT-2 or MT-4 cells.

Azacitidine↗
PubMed2001

Pesticidal properties of parthenin (from Parthenium hysterophorus) and related compounds.

Eleven sesquiterpene lactone derivatives of parthenin (1), obtained from wild feverfew, Parthenium hysterophorus, were prepared by chemical and photochemical transformations. The compounds tested were a pyrazoline adduct (2) of parthenin, its cyclopropyl (3) and propenyl (4) derivatives, anhydroparthenin (5), a dihydro-deoxygenated product (6), a formate (7) and its corresponding alcohol (8) and acetate (9), a rearranged product (10), lactone (11) and hemiacetal (12). All these derivatives, along with parthenin, were tried for their antifeedant action against sixth-instar larvae of Spodoptera litura, for insecticidal activity against the adults of store grain pest Callosobruchus maculatus, for phytotoxic activity against Cassia tora, and for nematicidal activity against the juvenile stage-II (J2) of the root knot nematode Meloidogyne incognita. Antifeedent bioassay revealed that parthenin is moderately antifeedant. Among the derivatives, the saturated lactone (11) was found to be about 2.25 times more active than parthenin. The pyrazoline adduct (2) was found to be the most effective as an insecticide, with LC50 values after 24, 48 and 72 h of 96, 43 and 32 mg litre-1, respectively, which are comparable with neem extract. Compound 4 was found to be the most effective inhibitor of germination and seedling growth of C tora, with ID50 values for germination, plumule length and radicle length of 136, 326 and 172 compared with 364, 738 and 427 mg litre-1, respectively, for parthenin. Compound 10 was found to be the most effective in terms of nematicidal activity. The LC50 values for this compound were 273 and 104 mg litre-1, respectively, after 48 and 72 h compared with 862 and 512 mg litre-1 observed for parthenin after 48 and 72 h.

Animals↗
PubMed2001

Effect of a herbal protein CI-1, purified from Cajanus indicus on the ultrastructural study of hepatocytes, in models of liver failure in mice.

Ultrastructural changes in acute liver damage models in swiss albino mice (male, 30 g +/-2) induced by CCl(4) (0.1 ml/100 g); beta-galactosamine (500 mg/kg); paracetamol (300-500 mg/kg) and 40% ethanol (2 ml/100 g) were studied. Electron microscopical studies of hepatocytes of treated (hepatotoxins) mice showed-dilation of ER of both rough and smooth type with swollen mitochondria. Ethanol treated mouse hepatocytes showed giant mitochondria and presence of balloon cells. Nuclear changes showed increase in size and striking anisonucleosis, especially in CCl(4) and paracetamol treated mouse hepatocytes. Condensation of chromatin, nucleoli were fragmented and dispersed in beta-galactosamine induced hepatotoxic mice. These changes are remarkably striking in contrast to control animals. Treatment with CI-1, the herbal protein isolated from Cajanus indicus inhibited the pathogenesis of a majority of lesions produced by the hepatotoxins. Slender mitochondria, array of granular ER, presence of binucleated cells are the salient features of CI-1 treated hepatotoxic mice. Ultrastructurally, the hepatocytes of CI-1 treated mice were near normal. Thus, the herbal protein CI-1, may be a useful approach in the treatment of liver disorders for its potential in clinical medicine.

Acetaminophen↗
PubMed2001

Laparoscopic surgery during pregnancy.

Important factors in laparoscopic surgery during pregnancy are listed here: There is a risk of aspiration because of a hormonally induced decrease in lower esophageal sphincter tone and mechanical effects of a gravid uterus. Supine hypotensive syndrome because of aortocaval compression can be a major problem. Pneumoperitoneum during pregnancy results in more pronounced restrictive lung physiology. Avoid hypoxemia, hypotension, acidosis, hypoventilation, and hyperventilation. No anesthetic drugs have been proven to be teratogenic in humans. Surgery during pregnancy is associated with the delivery of low birth-weight, growth-restricted babies. Standard noninvasive monitoring could be sufficient for healthy parturients undergoing laparoscopic surgery. Fetal heart rate and uterine activity should be monitored pre- and postoperatively. Laparoscopic surgery during pregnancy is safe, has multiple advantages over open techniques, can be performed during all gestational ages, and does not require invasive or continuous fetal and uterine monitoring for routine cases; however, the anesthesiologist must be aware of the physiologic changes associated with pregnancy and the effects of positioning, and the consequences of CO2 pneumoperitoneum on the parturient and the fetus. Although no special monitoring is required in healthy parturients, each case must be assessed carefully, and invasive monitoring could be required in those patients with significant cardiovascular or pulmonary disease. Fetal heart rate should be assessed preoperatively and postoperatively. Surveillance with an external tocodynamometer should be instituted immediately preoperatively and postoperatively and tocolytic agents instituted if documented or perceived uterine activity is detected.

Female↗
PubMed2001

Can estrogen influence the response to noxious stimuli?

STUDY OBJECTIVES: To evaluate estrogen-induced alternations in noxious stimuli response. DESIGN: Randomized, prospective, double-blind study. SETTINGS: Tertiary-care academic medical center. PATIENTS: 40 ASA physical status I and II women at the beginning and conclusion of an in vitro fertilization stimulation cycle. INTERVENTIONS: Stimuli were applied to the fingers of the dominant hand via a Basile Analgesy-Meter, which applied increasing pressure (g/cm(2)) in a continuous fashion, and ice water immersion. MEASUREMENTS: Serum hormonal concentrations and responses to noxious (pressure and cold thermal) stimuli were studied. MAIN RESULTS: Estrogen and progesterone concentrations changed from 377 +/- 323.42 pg/mL to 2078.05 +/- 1175.92 pg/mL (p < 0.001) and 1.20 +/- 0.56 to 1.03 +/- 0.35 ng/mL (p = NS), respectively. Although no significant difference was noted in the response to pressure (16.92 +/- 4.41 to 17.85 +/- 4.95 g/cm(2)), a significant reduction in the tolerance to ice water immersion (34.18 +/- 28.29 to 24.05 +/- 23.02 s) was observed. CONCLUSIONS: High estrogen concentrations are associated with significantly lower tolerance to cold, but not pressure stimuli.

Adult↗
PubMed2001

Transcutaneous electrical nerve stimulation does not augment epidural labor analgesia.

STUDY OBJECTIVE: To evaluate whether transcutaneous electrical nerve stimulation (TENS) can increase the quality and duration of an initiation dose of bupivacaine used for the establishment of epidural labor analgesia. DESIGN: Randomized, double-blind study. SETTING: Tertiary-care academic medical center. PATIENTS: 40 ASA physical status I and II parturients in early, active spontaneous labor with a singleton, vertex term fetus, and requesting analgesia. INTERVENTIONS: A standardized epidural technique with either an active or inactive TENS unit was performed. Before epidural placement, TENS intensity thresholds were determined with electrodes placed over the paraspinus muscles at T(10)-L(1), and S(2)-S(4); TENS settings for mode, cycle, and pulse width were standardized. MEASUREMENTS: Data were collected at timed intervals on pain as measured by visual analog scale (VAS), sensory level (pinprick), motor blockade (Bromage score), cervical dilation, and duration of analgesia. MAIN RESULTS: The duration of analgesia produced by the initial dose of epidural bupivacaine did not differ between groups (TENS turned off 82.3 +/- 26 [mean +/- SD] vs. TENS activated 80.7 +/- 40 min, p = 0.88). Kaplan-Meier survival analysis and Mantel-Cox log rank analysis showed no difference between the two treatments (p = 0.75). No difference in the quality of analgesia was observed between the two groups. CONCLUSIONS: In healthy laboring parturients, the application of a TENS unit did not alter the quality or duration of an initiation dose of bupivacaine utilized for the establishment of epidural labor analgesia.

Adult↗
PubMed2001

Use of variability in the stage-specific transcription levels of Plasmodium falciparum in the selection of target genes.

The malarial parasite Plasmodium falciparum exhibits several morphological and developmental stages. We have quantified the level of expression of a battery of genes in the ring and trophozoite stage-two of the most prominent stages in the erythrocytic development of the parasite. Using optimized RT-PCR, we observed that some of the genes show a large variation in stage-specific expression. We have also correlated the level of mRNA expression (of the target enzyme) to its metabolic requirement using specific inhibitors. This protocol gives us a handle to identify vulnerable target genes that could be used to develop antimalarials.

Animals↗
PubMed2001

Ultraviolet irradiation increases matrix metalloproteinase-8 protein in human skin in vivo.

Humans express three distinct collagenases, MMP-1, MMP-8, and MMP-13, that initiate degradation of fibrillar type I collagen. We have previously reported that ultraviolet irradiation causes increased expression of MMP-1, but not MMP-13, in keratinocytes and fibroblasts in human skin in vivo. We report here that ultraviolet irradiation increases expression of MMP-8 in human skin in vivo. Western analysis revealed that levels of the full-length, 85 kDa proenzyme form of MMP-8 increased significantly within 8 h post ultraviolet irradiation (2 minimal erythema doses). Increased full-length MMP-8 protein was associated with infiltration into the skin of neutrophils, which are the major cell type that expresses MMP-8. Immunofluorescence revealed coexpression of MMP-8 and neutrophil elastase, a marker for neutrophils. Immunohistology demonstrated MMP-8 expression in neutrophils in the papillary dermis between 4 and 8 h post ultraviolet irradiation, and in the epidermis at 24 h post radiation. MMP-8 mRNA expression was not detected in nonirradiated or ultraviolet-irradiated human skin, indicating that increased MMP-8 following ultraviolet irradiation resulted from preexisting MMP-8 protein in infiltrating neutrophils. Pretreatment of skin with the glucocorticoid clobetasol, but not all-trans retinoic acid, significantly blocked ultraviolet-induced increases in MMP-8 protein levels, and neutrophil infiltration. In contrast, all-trans retinoic acid and clobetasol were equally effective in blocking ultraviolet induction of MMP-1 and degradation of collagen in human skin in vivo. Taken together, these data demonstrate that ultraviolet irradiation increases MMP-8 protein, which exists predominantly in a latent form within neutrophils, in human skin in vivo. Although ultraviolet irradiation induces both MMP-1 and MMP-8, ultraviolet-induced collagen degradation is initiated primarily by MMP-1, with little, if any, contribution by MMP-8.

Adult↗
PubMed2001

Magnetization transfer MR imaging correlation with histopathology in intracranial tuberculomas.

OBJECTIVE: The purpose of this study was to correlate the differences in the magnetization transfer (MT) ratios of different components of the tuberculoma with histopathology and to see whether MT or conventional MR imaging correlates better with histopathology. METHODS: MT T1 and conventional spin echo MR imaging was performed in six patients with intracranial tuberculomas. The tuberculomas were excised as a single mass and ex vivo MR imaging was performed using the same protocol. The gross histopathology was compared with in vivo imaging with respect to the MR signal intensity (MT ratio) in all six specimens. RESULTS: The size of the tuberculomas was larger on MT T1-weighted images compared to T2-weighted images and matched the gross measurements of each specimen. The MT hyperintense rim matched the cellular component of the tuberculoma that was masked on T2-weighted images because of the associated perifocal oedema. The cellular component had a lower MT ratio compared to the necrotic components. CONCLUSION: The outer hyperintense rim and hyperintense strands are due to the cellular infiltrate, noncaseating granulomas, and gliosis while the hypointense core represents solid caseation. The cellular outer rim shows lower MT ratio compared to the core of the tuberculoma. Histological correlation of the cellular and necrotic components of tuberculomas is best shown with MT T1 imaging.

Adult↗