Heteroepitaxial growth of strained multilayer superconducting thin films of Nd1.83Ce0.17CuOx/YBa2Cu3O7- delta.
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Biomedical subjects
Publications and source records attributed to R Gross.
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The nutritional status according to anthropometric data was assessed in 756 schoolchildren from 5 low-income state schools and in one private school in the same part of Rio de Janeiro, Brazil. The prevalence of stunting and wasting (cut-off point: less than 90% ht/age and less than 80% wt/ht) ranged in the public schools from 6.2 to 15.2% and 3.3 to 24.0%, respectively, whereas the figures for the private school were 2.3 and 3.5%, respectively. Much more obesity was found in the private school (18.0%) than in the state schools (0.8-6.2%). Nutritional problems seem to develop more severely in accordance with the increasing age of the children. Therefore it appears advisable to assess schoolchildren within the context of nutritional surveillance system.
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Yohimbine hydrochloride, an alpha 2-adrenoceptor antagonist, was administered (3.3 mg/kg i.v.) to anesthetized normal dogs provided with a T-shaped catheter inserted in the pancreaticoduodenal vein. The effects on blood glucose levels and pancreatic hormones were investigated. We show that yohimbine induced an immediate and pronounced stimulatory effect on insulin secretion accompanied by a clear decrease in blood glucose levels. Yohimbine also stimulated the pancreatic secretion of somatostatin and glucagon. However, the secretion kinetics were not the same for the three hormones: the stimulation was rapid and immediate for insulin and somatostatin, whereas it was progressive for glucagon. All these stimulatory effects were suppressed by propranolol, thus implicating beta-adrenergic mechanisms. Bilateral cervical vagotomy markedly reduced the immediate effect of yohimbine on insulin secretion, suggesting that a central neural pathway was implicated. In contrast, the progressive elevation in glucagon secretion was not decreased by vagotomy. Our results suggest that yohimbine stimulates, at least in part, insulin secretion by blocking central alpha 2-adrenoceptors.
The basic pharmacology of dihydropyridine Ca-agonists published so far (BAY k8644, CGP 28-392, H 160/51, YC 170, and 202-791) is described. The importance of the potency of the enantiomeres for the effect of a racemic compound is underlined. The Ca agonist prototype BAY k8644 leads to an increase of the maximal rate of rise of left ventricular pressure (LV(dP/dt)) and an increase of left ventricular stroke work in conscious dogs. When the vascular effects of BAY k8644 are counterbalanced by intravenous injection of sodium-nitroprusside, the left ventricular functions curves show markedly increased stroke work against the same mean arterial blood pressure at the same filling pressure. BAY k8644 stimulates the heart economically: the net efficiency in isolated working guinea-pig hearts is about 20%, identical to a stimulation by calcium or ouabain. Cardiotonic drugs acting via cAMP-dependent mechanisms like isoprenaline, amrinone, or pimobendane however, stimulate the heart about 1/3 less economically. The mechanism of action of Ca-agonists is explained from electrophysiological findings: Ca-agonistic dihydropyridines increase the open probability of the Ca-channels by a shift of the open-probability curve to more negative membrane potentials. As a consequence, the steady-state inactivation curve of the Ca-channel is also shifted in the same direction. While the effect on open-probability is the underlying mechanism for Ca-agonism, the latter effect results in Ca-antagonism. Therefore, depending on drug concentration and on membrane resting potential, a single chemical compound can act either as a Ca-agonist or a Ca-antagonist. A kinetic model of dihydropyridine action on the Ca-channel is described.
The bvg locus of Bordetella pertussis is required for coordinate regulation of several factors associated with virulence. The control system is modulated by various environmental signals, including low temperature, MgSO4, and nicotinic acid. The nucleotide sequence of the bvg region has been determined and three open reading frames, bvgA, bvgB, and bvgC, are present. Twelve-base-pair linker insertion mutations in any of these open reading frames result in a Bvg- phenotype. The predicted protein products of bvgA and bvgC share homology with a family of prokaryotic regulatory proteins that respond to environmental stimuli and are members of two-component sensory transduction systems. We propose a model in which BvgB and the N-terminal portion of BvgC are localized in the periplasm. Environmental signals are recognized, transduced to the cytoplasmic portion of BvgC, and then transmitted to BvgA, a positive regulator of transcription.
Pertussis toxin (PT) is the major virulence factor of Bordetella pertussis. The cloning and nucleotide sequencing of the PT genes from B. pertussis, Bordetella parapertussis and Bordetella bronchiseptica has elucidated the evolution of the Bordetella species and allowed considerable advances towards the understanding of their gene expression and the development of safer vaccines against pertussis.
Bacteria can respond to a variety of environmental stimuli by means of systems generally composed of two proteins. The first protein (sensor or transmitter) is usually a transmembrane protein with cytoplasmic and extracytoplasmic domains. The extracytoplasmic domain (sensor) senses the environment and transfers the signal through the transmembrane domain to the cytoplasmic domain (transmitter), which has kinase activity. The second protein is located in the cytoplasm and contains an amino-terminal domain (receiver), which can be phosphorylated by the transmitter, and a carboxy-terminal region (regulator), which regulates gene expression by binding to DNA. The transmitter and receiver modules (the kinase and its target) are conserved in all signal-transducing systems and are the 'core structure' of this two-component system. The sensors and the regulators vary according to the stimuli they respond to and the DNA structure they interact with. On the basis of their sequence homology, the proteins belonging to such two-component systems can be classified into different families, which are summarized in this review.
Previous studies have provided evidence for the presence on B cell membrane of adenosine receptors (P1-purinoceptors) of the A1-subtype which inhibit insulin secretion. In this work we have investigated the implication of a guanosine triphosphate (GTP) binding protein (G protein) in the A1 purinoceptor-induced inhibition of insulin secretion from the isolated perfused pancreas of the rat. A group of rats was treated with pertussis toxin (10 micrograms kg-1, i.v.) 28 h prior to pancreas extirpation. This treatment totally abolished the 50% decrease in insulin secretion induced by (+)-N6-phenylisopropyl adenosine (1.65 microM), a P1-purinoceptor agonist. These results indicate that the A1-receptor-mediated inhibition of insulin secretion involves a pertussis toxin-sensitive G protein.
The effect of a stable structural analogue of adenosine, 5'-N-ethylcarboxamidoadenosine (NECA), was studied on glucagon secretion induced by acetylcholine (ACh) in the isolated perfused pancreas of the newborn dog. The perfusion solution contained a physiological concentration of glucose (4.2 mM). In the first set of experiments, ACh (0.5 microM) infused alone for 10 min induced a significant rise of glucagon secretion (370 +/- 98%, 4 min after the beginning of infusion). In the second set, NECA (2.2 nM) infused 10 min before ACh administration, had no effect per se, but considerably increased the response to ACh (929 +/- 262% of basal value within 3 min). So, the more specific A2 purinoceptor agonist, NECA, potentiated glucagon secretion induced by the cholinoceptor agonist, ACh.
1. The effects of exogenous adenine nucleotides and structural analogues on the biphasic insulin response to an increase of glucose concentration in the physiological range (from 4.2 to 8.3 mM) were studied in the isolated perfused rat pancreas. Purinoceptor agonists were added either simultaneously or 15 min before increasing glucose. 2. ATP and ADP at 16.5 microM were ineffective per se in the presence of the non stimulatory glucose concentration (4.2 mM) but markedly potentiated the biphasic insulin response to glucose rise in both experimental protocols. 3. Two more stable analogues of ATP and ADP (adenylylimidodiphosphate and alpha, beta-methylene ADP (alpha, beta-MeADP)) at 16.5 microM behaved like the natural compounds: they were ineffective at a glucose concentration of 4.2 mM and potentiated both phases of insulin response to glucose rise. 4. alpha, beta-MeATP added simultaneously with the high glucose concentration, markedly potentiated the first phase of insulin response to glucose rise but did not potentiate the second one. When alpha, beta-MeATP infusion began 15 min before glucose rise, the biphasic response to glucose was not potentiated, in contrast to what occurred with ATP. 5. In the presence of alpha, beta-MeATP, the ATP potentiating effect was unaffected. 6. It is concluded that ATP and ADP, via activation of beta cell P2 gamma purinoceptors, potentiates the biphasic insulin response to an increase of glucose concentration. On the other hand, alpha, beta-MeATP did not behave like natural and other structural analogues of ATP and ADP: this difference appears not to be the consequence of desensitization of beta cell P2 gamma purinoceptors by alpha, beta-MeATP.
Previous analysis of the pertussis toxin (PT) promoter has shown that expression of PT requires a trans-activating factor encoded by the vir locus and a 170-base-pair DNA sequence upstream from the transcription start site containing a 21-base-pair direct repeat sequence crucial trans-activation (R. Gross and R. Rappuoli, Proc. Natl. Acad. Sci. USA 85:3913-3917, 1988). In this paper we extend the analysis to the modulative response to environmental stimuli. We show that modulation acts at the transcriptional level and occurs only in phase I bacteria. Modulation also requires a functional vir locus and the same promoter region of 170 base pairs. We show that, in addition to the previously identified direct repeat, even the sequences downstream from position -117 are required for trans-activation and modulation and that the deletion of four cytosine residues at position -31 causes the inactivation of the promoter. The kinetics of the change in transcription show that the PT promoter can be shut off very rapidly by adding 50 mM MgSO4 to the medium, whereas resumption of transcription after removal of the modulative agents from the medium is slow.
To investigate whether systemic insulin levels can influence somatostatin-like immunoreactivity and insulin-like immunoreactivity concentrations in the rat submandibular salivary glands, we measured the concentrations of the two peptides in an experimental group rendered diabetic by streptozotocin administration. The diabetic group showed a low plasma level of insulin compared with the control group: 0.5 +/- 0.1 vs 3.5 +/- 0.8 micrograms/l, (P less than 0.01). Concomitantly, they exhibited clear glucosuria and a blood glucose level which was four times higher than in normal animals: 35.5 +/- 1.4 vs 8.8 +/- 0.8 mmol/l, (P less than 0.001). The two peptide concentrations in the submandibular glands of diabetic rats showed an increase compared with controls: 42.9 +/- 4.7 protein vs 24.7 +/- 3.1 pg/mg protein (P less than 0.001) and 34.9 +/- 4.9 protein vs 18.4 +/- 4.0 pg/mg protein (P less than 0.01), for insulin-like immunoreactivity concentration and somatostatin-like immunoreactivity concentration, respectively. Chronic insulin treatment of diabetic rats reversed the increase in somatostatin, but had no effect on the increase in insulin-like immunoreactivity concentration. A negative correlation (r = 0.24, P less than 0.05) was found between the plasma insulin level and the somatostatin concentration of the submandibular glands. Our results suggest that the submandibular glands of rats may participate in the peripheral regulation of glucose homeostasis.
Insulin and pancreatic somatostatin secretions were studied after stimulation with an arginine infusion (5 mmol/l) in isolated perfused pancreata of adult streptozotocin-diabetic rats. In the presence of 2.8 mmol/l glucose, arginine clearly stimulated insulin and somatostatin secretions in diabetic rats, whereas it was ineffective in normal rats. Thus, not only the B-cells, but also the D-cells of the pancreas from streptozotocin-diabetic rats are hypersensitive to arginine. The infusion of insulin (4 U/l) did not modify this hypersensitivity of the D-cells to arginine in pancreata of streptozotocin-diabetic rats.
During the second half of 1986 the health and nutritional status of 254 children aged up to six years was studied, as well as the socio-economic situation of their parents in two favelas (shantytowns) in Belo Horizonte, Brazil. The nutritional status of the children was characterized by stunting (Z-score: 20.1% less than -2) but not by wasting (Z-score: 3.7% less than -2). Consideration was also given to how far stunting was caused by high morbidity such as acute respiratory infections (point prevalence: 38.5%), diarrheal diseases (point prevalence: 11.5%) and parasitosis (point prevalence: 70.3%). Furthermore, anemia (point prevalence: 29.7%) appeared as another health problem. The most important determinant of anthropometric indices turned out to be the mother's schooling. From the present data it can be hypothesized that the nutritional status of the children was limited less by the lack of food than by their poor health status.