Intermittent positive pressure ventilation in a neonatal intensive care unit: Hyderabad experience.
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Female↗
Biomedical subjects
S Roy
Publications and source records attributed to S Roy.
Prevalence and determinants of central obesity and age-specific waist:hip ratio of people in five cities: the Indian Women's Health Study.
OBJECTIVE: To study the prevalence of central obesity and age-specific waist:hip ratio of urban women from five Indian cities. DESIGN AND SETTING: Cross-sectional surveys were conducted in 6-12 urban streets in different parts of India using similar methods of sample selection and criteria of diagnosis. SUBJECTS AND METHODS: We randomly selected 3212 women, aged 25-64 years, from Moradabad (n = 902), Trivandrum (n = 760), Calcutta (n = 365), Nagpur (n = 405), and Bombay (n = 780). Evaluation was by a questionnaire administered by a physician and a dietician, a physical examination, and anthropometric measurements. RESULTS: The overall prevalence of central obesity among the total number of women was 55.0%, with the highest prevalence in Calcutta (62.2%) and the lowest in Bombay (47.4%). Waist:hip ratio was 0.85 +/- 0.13 (mean +/- SD) with the highest ratio for women in Calcutta (0.87 +/- 0.12) and the lowest for women in Moradabad (0.84 +/- 0.16). After pooling of data from all five cities, multivariate logistic regression analysis showed that, regardless of age, body mass index (> 23 kg/m2; odds ratio 1.12), sedentary lifestyle (odds ratio 2.51), and family history of obesity (odds ratio 2.15) were strongly associated with central obesity. Excess intake of fat was weakly associated with central obesity but age was not a risk factor for central obesity, although the prevalence was highest among those aged over 55 years in Moradabad, Calcutta, and Nagpur. CONCLUSIONS: The overall prevalence of central obesity among the urban women of India has increased, more so in Calcutta and Trivandrum. Body mass index, sedentary lifestyle, and family history of excess intake of fat were significant risk factors for central obesity.
Adult↗
Outpatient anesthesia in oral and maxillofacial surgery.
An integral part of the specialty of oral and maxillofacial surgery is intra-operative anxiety and pain control with the use of inhalation and intravenous agents. The safety of these agents when used by trained practitioners and staff in properly equipped facilities is well-documented. The purpose of this article is to review the most common sedative agents currently used in the oral and maxillofacial surgery outpatient setting.
Ambulatory Surgical Procedures↗
Targeting the tumor vasculature: inhibition of tumor growth by a vascular endothelial growth factor-toxin conjugate.
Tumor-derived vascular endothelial growth factor (VEGF)/ vascular permeability factor (VPF) plays an important role in neovascularization and the development of tumor stroma. Furthermore, VEGF receptors are over-expressed in the endothelial cells of tumor vasculature and almost non-detectable in the vascular endothelium of adjoining normal tissues. The differential expression of receptor offers a selective advantage for targeting cytotoxic toxin polypeptides. We have prepared a vascular targeting reagent by chemically linking recombinant VEGF to a truncated form of diphtheria toxin. The VEGF-toxin conjugate was selectively toxic to endothelial cell lines and inhibited experimental neovascularization of the chick chorioallantoic membrane. In the present study, we examined the effects of VEGF-toxin conjugate on solid tumor growth. Athymic nude mice with established subcutaneous tumors were treated with daily intraperitoneal injections of the VEGF-toxin conjugate or free toxin. When compared with control animals treated with the toxin polypeptide alone, the conjugate-treated animals displayed a significant inhibition of tumor growth. Histological analysis of tumors from conjugate-treated animals revealed hemorrhagic necrosis consistent with a vascular-mediated injury. In contrast, highly vascularized normal tissues from conjugate-treated animals demonstrated no evidence of hemorrhage or tissue injury. The conjugate was well tolerated without apparent toxicities. Our results illustrate the anti-tumor activity of a VEGF-toxin conjugate selectively targeting the tumor neovasculature.
Animals↗
Prediction of Solubility of Nonpolar Gases in Micellar Solutions of Ionic Surfactants
The solubilities of methane, carbon dioxide, ethane, and propane have been determined experimentally at 1 atm partial pressure and 25°C in aqueous solutions of sodium dodecyl sulfate and cetyltrimethylammonium bromide. For this purpose a specially developed apparatus is used, which is relatively simple compared to those reported in the literature hitherto. Above the CMC, the solubility of each gas increases linearly with surfactant concentration indicating micellar solubilization. The degree of solubilization is greatest for propane and decreases in the order propane > ethane > carbon dioxide > methane. Both the length of the alkyl chain and the properties of the head-group region (i.e., the micelle-water interfacial tension) are observed to determine the intramicellar solubility. A method for estimating the solubilities is also proposed based on the rationale that the micellar phase may be represented by a droplet of a "model solvent" into which the solubilizate molecule dissolves as it would in a bulk solvent. The mixture of the solute species and the model solvent is assumed to behave as a regular solution. Accordingly, a characteristic solubility parameter is estimated for the model solvent from the interaction potential between two adjacent surfactant molecules in a micelle. The solubility computed using the regular solution approximation is further corrected for the Laplace pressure that acts across the curved micelle-water interface and generally reduces the intramicellar solubility. It is concluded that for small nonpolar solutes, micellar solubilities may be reasonably well predicted by assuming that the model solvent has a solubilizing capacity (i.e., solubility parameter) close to that of a bulk equivalent alkane. Copyright 1997 Academic Press. Copyright 1997Academic Press
Journal Article↗
Monochloramine inhibits phorbol ester-inducible neutrophil respiratory burst activation and T cell interleukin-2 receptor expression by inhibiting inducible protein kinase C activity.
Monochloramine derivatives are long lived physiological oxidants produced by neutrophils during the respiratory burst. The effects of chemically prepared monochloramine (NH2Cl) on protein kinase C (PKC) and PKC-mediated cellular responses were studied in elicited rat peritoneal neutrophils and human Jurkat T cells. Neutrophils pretreated with NH2Cl (30-50 microM) showed a marked decrease in the respiratory burst activity induced by phorbol 12-myristate 13-acetate (PMA), which is a potent PKC activator. These cells, however, were viable and showed a complete respiratory burst upon arachidonic acid stimulation, which induces the respiratory burst by a PKC-independent mechanism. The NH2Cl-treated neutrophils showed a decrease in both PKC activity and PMA-induced phosphorylation of a 47-kDa protein, which corresponds to the cytosolic factor of NADPH oxidase, p47(phox). Jurkat T cells pretreated with NH2Cl (20-70 microM) showed a decrease in the expression of the interleukin-2 receptor alpha chain following PMA stimulation. This was also accompanied by a decrease in both PKC activity and nuclear transcription factor-kappaB activation, also without loss of cell viability. These results show that NH2Cl inhibits PKC-mediated cellular responses through inhibition of the inducible PKC activity.
Ammonium Chloride↗
Glutathione regulation of tumor necrosis factor-alpha-induced NF-kappa B activation in skeletal muscle-derived L6 cells.
TNF alpha is implicated in several skeletal muscle pathologies including muscle wasting of cachexia. Muscle wasting and other conditions such as physical exercise and immobilization are also associated with disturbances in muscle glutathione status. Hence, it was of interest to investigate the role of endogenous glutathione status in TNF alpha induced NF-kappa B activation in skeletal muscle-derived cells. TNF alpha proved to be a potent inducer of transient NF-kappa B activation in L6 myoblasts. In buthioninesulfoximine (BSO) treated cells, TNF alpha induced NF-kappa B activation was markedly potentiated suggesting that such activation is sensitive to cellular GSH, but may have been independent of high levels of intracellular GSSG. Because this activation was inhibited by the antioxidant pyrrolidinedithiocarbamate (PDTC) the involvement of reactive oxygen species in this activation system seems likely. NF-kappa B activation in L6 cells was also observed in response to direct H2O2 treatment. Results from GSSG reductase inhibited cells suggest that GSSG may participate in, but is not required for, TNF alpha induced NF-kappa B activation. The inhibitory effect of PDTC on NF-kappa B activation correlated with its effect on ICAM-1 expression suggesting that this GSH status modifying agent not only influenced nuclear translocation of NF-kappa B proteins but also regulated kappa B dependent transcription.
Animals↗
Activity of plasma membrane-recruited Raf-1 is regulated by Ras via the Raf zinc finger.
Ras recruits Raf to the plasma membrane for activation by a combination of tyrosine phosphorylation and other as yet undefined mechanism(s). We show here that the Raf zinc finger is not required for plasma membrane recruitment of Raf by Ras but is essential for full activation of Raf at the plasma membrane. Membrane targeting cannot compensate for the absence of the zinc finger. One facet of the zinc finger activation defect is revealed using a constitutively activated Raf mutant. Targeting Raf Y340D,Y341D to the plasma membrane increments activity, but full activation requires coexpression with activated Ras. This sensitivity to regulation by Ras at the plasma membrane is abrogated by mutations in the Raf zinc finger but is unaffected by mutation of the minimal Ras binding domain. These data show for the first time that Ras has two separate roles in Raf activation: recruitment of Raf to the plasma membrane through an interaction with the minimal Ras binding domain and activation of membrane-localized Raf via a mechanism that requires the Raf zinc finger.
Animals↗
ACE inhibition: postsynaptic adrenergic sympatholytic action in men.
BACKGROUND: The mechanisms by which ACE inhibitors produce a sustained clinical benefit are not entirely clear but may involve the sympathetic nervous system. We compared the effect of local brachial artery infusions of an ACE inhibitor (perindoprilat) with the effect of placebo (0.9% NaCl) on endogenously mediated (lower body negative pressure [LBNP]) and exogenously mediated (brachial artery infusions of norepinephrine) sympathetic vasoconstriction. METHODS AND RESULTS: Eight healthy, normotensive male volunteers (20 to 32 years) were studied on one occasion. Forearm blood flow (FABF; mL x dL forearm(-1) x min(-1)) responses to LBNP (-20 cm H2O) and increasing increments of norepinephrine (60, 120, and 240 pmol/min) were compared when coinfused with placebo and perindoprilat (5 nmol/mL). FABF was measured simultaneously in both arms by venous occlusion plethysmography with mercury-in-Silastic strain gauges with drugs infused locally at the left brachial artery. The right arm served as a control. Baseline FABFs did not differ between the infused and control arms (3.04+/-0.52 versus 3.05+/-0.42 mL x dL forearm(-1) x min(-1); P=.98). Perindoprilat did not alter FABF when infused alone, but the FABF response to LBNP in the infused arm was attenuated during the perindoprilat infusion compared with placebo (-17.8+/-4.3% versus -33.8+/-3.1%, respectively; P=.015). The FABF response to the maximum dose of norepinephrine was also attenuated during the perindoprilat infusion compared with placebo (-28.3+/-1.4% versus -36.9+/-2.8%, respectively; P=.015). The mean slope of the FABF (log transformed) versus norepinephrine dose-response curve was significantly attenuated by perindoprilat compared with placebo (-0.11+/-0.019 versus -0.02+/-0.02; P=.001). CONCLUSIONS: We conclude that ACE inhibition has a significant postsynaptic sympatholytic effect in the forearm circulation of men.
Adult↗
A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis.
There is compelling evidence that members of the caspase (interleukin-1beta converting enzyme/CED-3) family of cysteine proteases and the cytotoxic lymphocyte-derived serine protease granzyme B play essential roles in mammalian apoptosis. Here we use a novel method employing a positional scanning substrate combinatorial library to rigorously define their individual specificities. The results divide these proteases into three distinct groups and suggest that several have redundant functions. The specificity of caspases 2, 3, and 7 and Caenorhabditis elegans CED-3 (DEXD) suggests that all of these enzymes function to incapacitate essential homeostatic pathways during the effector phase of apoptosis. In contrast, the optimal sequence for caspases 6, 8, and 9 and granzyme B ((I/L/V)EXD) resembles activation sites in effector caspase proenzymes, consistent with a role for these enzymes as upstream components in a proteolytic cascade that amplifies the death signal.
Amino Acid Sequence↗
Morphine inhibits transcriptional activation of IL-2 in mouse thymocytes.
Chronic treatment of mice with morphine affects the proliferation, differentiation, and function of immune cells. In the present study, we investigated the mechanism by which morphine inhibits phytohemagglutinin (PHA)/interleukin-1 (IL-1)-induced thymocyte proliferation. When compared to control cultures, morphine-treated thymocytes showed decreased steady-state levels of bioactive IL-2 and IL-2 mRNA. The reduced IL-2 concentration and reduced transcript levels correlated well with a decreased rate of synthesis of IL-2 mRNA as determined by nuclear runoff assays. Subsequent studies showed that morphine treatment affected transcriptional control elements of the IL-2 promoter by inhibiting the synthesis of a specific trans-activating nuclear factor, c-Fos. c-Fos mRNA levels measured by semiquantitative RT-PCR were significantly decreased in thymocytes following treatment with morphine and activation with PHA and IL-1. Under identical conditions, c-Jun mRNA levels were not altered. Electrophoretic mobility shift studies with the AP-1 consensus oligonucleotide showed significantly decreased levels of AP-1-protein complex formation in nuclear extracts prepared from morphine-treated cells. These studies demonstrate for the first time that opioid alkaloids such as morphine can impair mitogen-lymphokine-activated thymocyte proliferation by interfering with transcriptional activation of the IL-2 gene.
Animals↗
Expression of human cholesterol 7alpha-hydroxylase in atherosclerosis-susceptible mice via adenovirus infection.
Adenovirus is a vector for the delivery of genes mainly to the liver. Short-term (approximately 3 days) studies using adenovirus transfection have provided valuable insights into how genes can complement normal and pathological phenotypes. When atherosclerosis-susceptible C57BL/6 mice were infected with an adenovirus vector containing the human 7alpha-hydroxylate cDNA (AV17h1) and fed on a chow diet, human 7alpha-hydroxylase mRNA and enzyme activity doubled compared with that in mice infected with an adenovirus vector (AV1Null) alone. In AV17h1-infected mice fed on a high fat cholic acid (HFCA) diet, mRNA expression and activity of both the endogenous and adenovirus (human) 7alpha-hydroxylase were repressed. AV17h1-infected mice fed on a HFCA diet and killed at mid-light had increased 7alpha-hydroxylase activity and mRNA compared with mice killed at mid-dark. Since expression of AV17h1 is driven by a constitutive Rous sarcoma virus promoter, the repression of human 7alpha-hydroxylase by the HFCA diet was unexpected. In spite of this post-transcriptional repression by the HFCA diet, AV17h1-infected mice expressed the human 7alpha-hydroxylase mRNA, causing its enzyme activity to be 3-fold greater than in AV1Null-infected mice. In AV17h1-infected mice, the 7alpha-hydroxylase enzyme activity varied as a linear function of human mRNA abundance. In conclusion, the accumulation of apolipoprotein B-containing lipoproteins in plasma of C57BL/6 mice fed on the HFCA diet was not reduced by longer-term (2 weeks) 7alpha-hydroxylase expression, probably because of its diminished expression caused by the diet and hepatic inflammation from the adenovirus infection. These results may suggest that adenovirus is effective in promoting longer-term (2 weeks) expression of 7alpha-hydroxylase.
Adenoviridae Infections↗
Positional isomers of monopegylated interferon alpha-2a: isolation, characterization, and biological activity.
The success of recombinant interferon alpha in the clinic in part is limited by two properties of the protein: short serum half-life and immunogenicity. To improve these properties, interferon alpha-2a was conjugated with polyethylene glycol (PEG-5000). A homogeneous preparation of monopegylated interferon alpha-2a was subjected to vigorous analytical and activity characterization. A newly developed ampholyte-free chromatofocussing-like cation-exchange HPLC method utilizing a sulfopropyl resin was used to separate the monopegylated protein into 11 species. Peptide mapping, sequencing, and mass spectrometric analyses indicated that these species are positional isomers where each isomer represents a single polymer molecule conjugated to one specific lysine residue. No species with a modification at the amino terminus was observed. All 11 isomers show antiviral and antiproliferative activities in the same range as the parent monopegylated interferon alpha-2a.
Animals↗
Elderberry (Sambucus nigra) bark contains two structurally different Neu5Ac(alpha2,6)Gal/GalNAc-binding type 2 ribosome-inactivating proteins.
A second NeuAc(alpha2,6)Gal/GalNAc binding type 2 ribosome-inactivating protein (RIP), called SNAI' has been isolated from elderberry (Sambucus nigra) bark. SNAI' is a minor bark protein which closely resembles the previously described major Neu5Ac(alpha2,6)Gal/GalNAc binding type 2 RIP called SNAI with respect to its carbohydrate-binding specificity and ribosome-inactivating activity but has a different molecular structure. Molecular cloning revealed that the deduced amino acid sequence of SNAI' is highly similar to that of SNAI and that the difference in molecular structure between both proteins relies on a single cysteine residue present in the B chain of SNAI but absent from SNAI'. The isolation of SNAI' not only identifies a minor bark protein as a type 2 RIP but also further emphasizes the complexity of the type 2 RIP/lectin mixture present in the bark of elderberry.
Amino Acid Sequence↗
Muscles in the Drosophila second thoracic segment are patterned independently of autonomous homeotic gene function.
BACKGROUND: In Drosophila, segment-specific muscle pattern is thought to be determined by the autonomous function of homeotic selector genes in the mesoderm in combination with inductive cues from the developing epidermis and nervous system. Here, we have examined the roles of homeotic genes in the patterning of the somatic muscles of the thoracic segments of Drosophila. RESULTS: We determined the expression patterns of homeoproteins in the mesoderm of the thoracic segments during embryonic and adult development. We found that, unlike the mesoderm of the first and third thoracic segments which express Sex combs reduced and Antennapedia (Antp), respectively, the mesoderm of the second thoracic segment does not express any known homeotic selector gene of the Antp or bithorax complex. In animals homozygous for Antp null mutations, the muscles of the second thoracic segment were affected in the embryo, probably as an indirect consequence of its requirement in the ectoderm. Animals that specifically lacked Antp function in the mesoderm, but expressed the gene in the epidermis, developed with a normal muscle pattern in the second thoracic segment. Furthermore, specific ectopic expression of Antp and other homeotic selector genes in the mesoderm of the second thoracic segment respecified its muscle pattern, indicating that these genes are not required autonomously during muscle development in this segment. Finally, we showed that Antp continues to be expressed in the mesoderm of the homeotically transformed third thoracic segment in the 'four-winged fly', and suggest that this is a likely reason for the failure of flight muscle development in the transformed segment. CONCLUSIONS: We present a model for muscle development in the second thoracic segment whereby mesodermal properties are specified entirely by induction, in contrast to muscle development in other segments, where autonomous function for homeotic selector genes is also required.
Animals↗
Interaction of Gal repressor with inducer and operator: induction of gal transcription from repressor-bound DNA.
Gal repressor inhibits transcription from the gal promoter (P1) when it binds to the cognate operator (O(E)). The repression is relieved by the presence of the inducer D-galactose. Compared with its interaction with free repressor, D-galactose binds to the repressor-operator complex with 10-fold reduced affinity as determined by fluorescence enhancement measurements. Thermodynamic analysis and fluorescence anisotropy showed that the stability of the repressor-operator complex is reduced by only 7-fold by the presence of the inducer in the complex. The formation of the inducer-repressor-operator ternary complex has been confirmed by CD spectral analysis. Fluorescence spectroscopy and energy transfer experiments suggest that individual allosteric effects of the two ligands, inducer and operator, on Gal repressor are responsible for the slightly weakened stability of the ternary complex compared with the stability of the inducer-repressor and repressor-operator complexes. In vitro transcription results demonstrated full derepression of transcription of the P1 promoter under conditions in which the concentrations of the inducer-repressor binary complex are severalfold higher than the dissociation constant of the inducer-repressor-operator ternary complex into inducer-repressor and free DNA. These results strongly suggest that the inducer binding to the repressor-operator complex does not lead to dissociation of the repressor from the operator during transcription induction. Because Gal repressor inhibits transcription by modulating the alpha subunit of the P1-bound RNA polymerase, we conclude that the inducer binding to the operator-bound repressor only allosterically relieves the inhibitory effect of repressor on RNA polymerase without dissociating the repressor from DNA.
Circular Dichroism↗
Modulation of cellular reducing equivalent homeostasis by alpha-lipoic acid. Mechanisms and implications for diabetes and ischemic injury.
The therapeutic potential of alpha-lipoic acid (thioctic acid) was evaluated with respect to its influence on cellular reducing equivalent homeostasis. The requirement of NADH and NADPH as cofactors in the cellular reduction of alpha-lipoic acid to dihydrolipoate has been reported in various cells and tissues. However, there is no direct evidence describing the influence of such reduction of alpha-lipoate on the levels of cellular reducing equivalents and homeostasis of the NAD(P)H/NAD(P) ratio. Treatment of the human Wurzburg T-cell line with 0.5 mM alpha-lipoate for 24 hr resulted in a 30% decrease in cellular NADH levels. alpha-Lipoate treatment also decreased cellular NADPH, but this effect was relatively less and slower compared with that of NADH. A concentration-dependent increase in glucose uptake was observed in Wurzburg cells treated with alpha-lipoate. Parallel decreases (30%) in cellular NADH/NAD+ and in lactate/pyruvate ratios were observed in alpha-lipoate-treated cells. Such a decrease in the NADH/NAD+ ratio following treatment with alpha-lipoate may have direct implications in diabetes, ischemia-reperfusion injury, and other pathologies where reductive (high NADH/NAD+ ratio) and oxidant (excess reactive oxygen species) imbalances are considered as major factors contributing to metabolic disorders. Under conditions of reductive stress, alpha-lipoate decreases high NADH levels in the cell by utilizing it as a co-factor for its own reduction process, whereas in oxidative stress both alpha-lipoate and its reduced form, dihydrolipoate, may protect by direct scavenging of free radicals and recycling other antioxidants from their oxidized forms.
Cells, Cultured↗
Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization.
Lipoic acid (thiotic acid) is being used as a dietary supplement, and as a therapeutic agent, and is reported to have beneficial effects in disorders associated with oxidative stress, but its mechanism of action remains unclear. We present evidence that lipoic acid induces a substantial increase in cellular reduced glutathione in cultured human Jurkat T cells human erythrocytes, C6 glial cells, NB41A3 neuroblastoma cells, and peripheral blood lymphocytes. The effect depends on metabolic reduction of lipoic acid to dihydrolipoic acid. Dihydrolipoic acid is released into the culture medium where it reduces cystine. Cysteine thus formed is readily taken up by the neutral amino acid transport system and utilized for glutathione synthesis. By this mechanism lipoic acid enables cystine to bypass the xc- transport system, which is weakly expressed in lymphocytes and inhibited by glutamate. Thereby lipoic acid enables the key enzyme of glutathione synthesis, gamma-glutamylcysteine synthetase, which is regulated by uptake-limited cysteine supply, to work at optimum conditions. Flow cytometric analysis of freshly prepared human peripheral blood lymphocytes, using monobromobimane labeling of cellular thiols, reveals that lipoic acid acts mainly to normalize a subpopulation of cells severely compromised in thiol status rather than to increase thiol content beyond physiological levels. Hence lipoic acid may have clinical relevance in restoration of severely glutathione deficient cells.
Animals↗