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H Rosenberg

Publications and source records attributed to H Rosenberg.

At least 19 recordsLinked to original sources
PubMed1992

Mutational analysis of the Escherichia coli phosphate-specific transport system, a member of the traffic ATPase (or ABC) family of membrane transporters. A role for proline residues in transmembrane helices.

The Escherichia coli Pst system is a periplasmic phosphate permease. A mutational analysis of the requirement for function of specific charged residues or proline residues in the two hydrophobic subunits (PstC and PstA) has been carried out. No residues, among 19 charged residues altered, were found to be essential for phosphate uptake, although some alterations resulted in partial effects. Evidence was obtained that the 3 residues, R220 in the PstA protein and R237 and E241 in the PstC protein, previously shown to be required for phosphate transport (Cox, G. B., Webb, D., Godovac-Zimmermann, J., and Rosenberg, H. (1988) J. Bacteriol. 170, 2283-2286; Cox, G. B., Webb, D., and Rosenberg, H. (1989) J. Bacteriol. 171, 1531-1534), interact with each other. A feature of the proposed structures of the PstA and PstC proteins was 2 pairs of proline residues in putative transmembrane helices 3 and 4. While individual substitutions of these proline residues by leucine resulted in loss of phosphate transport activity substitution by alanine only had partial effects. However, if the proline to alanine changes were paired then, depending on the particular subunit, markedly different effects were obtained. The double mutation in the PstA protein resulted in a permanently "closed" system, whereas the double mutation in the PstC protein resulted in a permanently "open" transport system.

ATP-Binding Cassette Transporters↗
PubMed1992

Evidence for the localization of a malignant hyperthermia susceptibility locus (MHS2) to human chromosome 17q.

Malignant hyperthermia susceptibility is a lethal autosomal dominant disorder of skeletal muscle metabolism that is triggered by all potent inhalation anesthetic gases. Recent linkage studies suggest a genetic locus for this disorder on 19q13.1. We have previously reported three unrelated families diagnosed with MHS that are unlinked to markers surrounding this locus on 19q13.1. In this report we extend these observations and present linkage studies on 16 MHS families. Four families (25%) were found linked to the region 19q12-q13.2 (Zmax = 2.96 with the ryanodine receptor at theta = 0.0). Five families (31%) were found closely linked to the anonymous marker NME1 (previously designated NM23) on chromosome 17q11.2-q24 (Zmax = 3.26 at theta = 0.0). Two families (13%) were clearly unlinked to either of these chromosomal regions. In five additional families, data were insufficient to determine their linkage status (they were potentially linked to two or more sites). The results of our heterogeneity analyses are consistent with the hypothesis that MHS can be caused in humans by any one of at least three distinct genetic loci. Furthermore, we provide preliminary linkage data suggesting the localization of a gene in human MHS to 17q11.2-q24 (MHS2), with a gene frequency of this putative locus approximately equal to that of the MHS1 locus on 19q.

Adult↗
PubMed1992

Skin nodules and macules resembling vasculitis in the antiphospholipid syndrome--a report of two cases.

Two patients who demonstrated skin lesions in the presence of antiphospholipid antibodies are documented. The first had a long history of recurrent painful nodules. She had also suffered two deep vein thromboses. The second developed a rash on the lower limbs resembling vasculitis which did not respond to prednisolone, but to low dose salicylate therapy. Histology in both patients revealed microthrombosis of cutaneous vessels.

Adult↗
PubMed1992

Perinatal assessment of cerebral flow velocity wave forms in the human fetus and neonate.

The temporal relationship between changes in cerebral Doppler flow velocity wave forms, ductal patency, blood gases, and blood pressure during the transition from intrauterine to newborn life was assessed longitudinally in 16 healthy term fetuses and newborns. Doppler flow velocity wave forms were obtained from fetal cerebral arteries (anterior cerebral, internal carotid, and basilar) before birth, within 8 h after birth, and again at 24 and 48 h after birth. The resistance index was used as a measure of vascular resistance. The resistance index of the cerebral arteries studied increased significantly between the antenatal and 8-h study periods. This was followed by a significant decrease below fetal levels by the 24-h study period, with little change thereafter. We conclude that in the newborn human, as in the newborn lamb, the transition from fetal to immediate newborn life is associated with an increase in cerebral vascular resistance and thus a decrease in cerebral blood flow in response to the increase in arterial oxygenation. The subsequent decrease in the cerebral resistance index between 8 and 24 h of life cannot be explained by a loss of ductal shunting nor by associated changes in newborn blood gases or blood pressure, but may rather reflect a remodeling of the circulation due to impedance matching.

Blood Flow Velocity↗
PubMed1992

A 10-year follow-up survey of acceptability of controlled drinking in Britain.

This study was designed to reassess the acceptability of controlled drinking (CD) approximately 10 years after Robertson and Heather's (1982) survey of British treatment providers. Sixty percent of a wide range of almost 300 targeted alcohol service agencies in Scotland, England and Wales responded to a mailed questionnaire. Three-quarters of these respondents reported that nonabstinence was an acceptable outcome goal. About half of the respondents who accept CD reported it as acceptable for only 1-25% of their clientele. Within the subgroup of outpatient agencies, almost one-third reported CD as appropriate for at least 50% of their clientele. Respondents endorsing CD rated severity of dependence, client attitudes and beliefs about controlled drinking and abstinence, drinking history, liver function test results and social stability/social relationships as the most important factors of those listed in selecting outcome goals. Respondents reportedly based acceptance or rejection of CD most frequently on their own professional experience and, to a lesser extent, on research evidence for or against CD and on agency policy.

Adult↗
PubMed1991

Relationships between block-of-twitch and train-of-four fade in the mouse phrenic nerve-diaphragm preparation.

The relationships between the block-of-twitch and train-of-four fade in the presence of nondepolarizing neuromuscular blocking drugs (d-tubocurarine, vecuronium and pancuronium) were examined in vitro by measuring the contractile tension from mouse phrenic nerve-diaphragm preparations. The slope of the block/fade relationship differed between onset of and recovery from neuromuscular block following single doses of d-tubocurarine, vecuronium or pancuronium. Decreasing the dose of d-tubocurarine or using a divided dose technique to accelerate onset (i.e., priming) increased the amount of fade for a given amount of block. In addition, the block/fade relationships for cumulative dosing and sequential dilution were the same when measurements were made at steady-state for several doses. It is concluded that the block/fade relationship in the mouse phrenic nerve-diaphragm preparation is variable, and is related to the time course of the neuromuscular block. In addition, the block/fade relationships for d-tubocurarine, vecuronium and pancuronium did not differ when determined at steady-state.

Animals↗
PubMed1991

Expanding applicability of transplantation after multiple prior palliative procedures. The Paediatric Heart Transplant Group.

The number of heart transplantations performed over the past 3 years has plateaued. However, the number of pediatric transplantations continues to slowly increase. Unlike adult heart transplantation, for which cardiomyopathy remains the most frequent indication, structural congenital heart disease is the primary indication in children. This report reviews our experience with orthotopic heart transplantation in the presence of structural congenital heart disease with and without prior palliative repair. The diagnoses included transposition of the great arteries, common atrium, left superior vena cava with and without a bridging innominate vein, dextrocardia, and univentricular configurations. The palliative repairs included Blalock-Taussig shunt, bilateral Glenn shunt, Fontan repair, and Mustard and Rastelli procedure. There were no early deaths. Two rejection-related late deaths have occurred at 8 months and at 3 years postoperatively. Extended use of donor tissue and modifications to surgical technique allowed for successful orthotopic heart transplantation in these patients who had structural congenital heart disease with and without prior surgical palliation.

Child↗
PubMed1991

Fatty acids markedly lower the threshold for halothane-induced calcium release from the terminal cisternae in human and porcine normal and malignant hyperthermia susceptible skeletal muscle.

Malignant hyperthermia is caused by an abnormal increase in Ca2+ levels in skeletal muscle in response to anesthetics, including halothane. Since fatty acid production is elevated in skeletal muscle from individuals with malignant hyperthermia, the effects of fatty acids on the threshold of halothane-induced Ca2+ release were examined. In the absence of fatty acids halothane caused Ca2+ release from porcine and human heavy sarcoplasmic reticulum fractions, but only at concentrations above the clinically relevant range. Oleic acid (20 microM), an unsaturated fatty acid, reduced the threshold at which halothane induced Ca2+ release to concentrations used for anesthesia. Stearic acid, a saturated fatty acid had considerably less effect on the threshold of halothane action. The greater sensitivity of malignant hyperthermia muscle to halothane can be explained by elevated fatty acid production.

Animals↗
PubMed1991

Evidence for genetic heterogeneity in malignant hyperthermia susceptibility.

Malignant hyperthermia susceptibility (MHS) is a clinically heterogeneous pharmacogenetic disorder characterized by accelerated metabolism, hyperthermia, and frequently muscle rigidity. MHS is elicited by all commonly used potent inhalation anesthetics and depolarizing neuromuscular blockers and remains an important cause of death due to anesthesia. Recent linkage studies suggest a single genetic locus for this disorder on chromosome 19q13.1. The results of our linkage analyses exclude several loci on 19q13.1 as a site for the gene(s) that produces the MHS phenotype in three unrelated families and clearly establish genetic heterogeneity in this disorder. These results are consistent with the hypothesis that the genetic defect that alters thermoregulation may vary in MHS and that clinical variability in the expression of MHS may be explained by genetic heterogeneity.

Chromosomes, Human, Pair 19↗
PubMed1991

Comparison of North American and European malignant hyperthermia group halothane contracture testing protocols in swine.

Different in vitro halothane testing procedures have been used in the European malignant hyperthermia (MH) Group Protocol (EMHGP) and the North American MH Group Protocol (NAMHGP), whereas the caffeine-testing protocols are very similar. The present study compares the two halothane-testing protocols in ten MH susceptible swine and in four control swine. Halothane contracture testing was conducted in vitro 12-52 days following the barnyard challenge that established the MH susceptibility of the swine. There was one false positive and one false negative halothane test by the EMHGP. The MH-equivocal category in the EMHGP, which is treated clinically as MH-susceptible, affords a margin of safety in such cases. In contrast, there were no false halothane tests by the NAMHGP. While some skeletal muscle strips from MH pigs were normal by both protocols (NAMHGP 30%; EMHGP 10%), the outcome of halothane testing by the NAMHGP was unaffected. The response to halothane 3% is reduced if preceded by the EMHGP, suggesting that simply adding halothane 3% to the end of the EMHGP does not permit a direct quantitative comparison to the NAMHGP. However, the diagnostic outcomes of the two approaches are similar.

Animals↗
PubMed1991

A blinded comparison of noninvasive, in vivo phosphorus nuclear magnetic resonance spectroscopy and the in vitro halothane/caffeine contracture test in the evaluation of malignant hyperthermia susceptibility.

Malignant hyperthermia (MH) is a potentially fatal, anesthetic-induced syndrome. Currently, the only accurate means of diagnosing susceptibility to this syndrome is the testing of biopsied skeletal muscle for its contracture response to halothane and caffeine. A less invasive means of diagnosis is needed. The authors previously reported that MH-susceptible patients studied by in vivo phosphorus nuclear magnetic resonance (31P NMR) spectroscopy demonstrated a higher resting inorganic phosphate (Pi) to phosphocreatine (PCr) ratio in their skeletal muscle, as well as a slower postexercise recovery of PCr/Pi, when compared to normal controls. In the present blinded study, the authors compared in vivo 31P NMR determination of resting Pi/PCr and recovery rate of PCr/Pi in forearm muscles to in vitro halothane/caffeine contracture test results in 42 patients. Forty-three control subjects were studied to establish normal NMR values of resting Pi/PCr and recovery rate of PCr/Pi. Their findings were compared with those of 27 patients shown to be MH-susceptible and 15 patients MH-negative by contracture testing. The MH-susceptible group had a significantly (P less than 0.005) higher resting Pi/PCr value (0.202 +/- 0.044) than either the MH-negative (0.152 +/- 0.043) or the control (0.141 +/- 0.026) group. The MH-susceptible group also had a significantly (P less than 0.02) slower postexercise recovery rate of PCr/Pi (1.50 +/- 0.872 PCr.Pi-1.min-1) than either the MH-negative (2.11 +/- 1.07 PCr.Pi-1.min-1) or control (2.25 +/- 0.828 PCr.Pi-1.min-1) group. Twenty-six of the 27 MH-susceptible patients demonstrated abnormal NMR test results (a resting Pi/PCr greater than or equal to 0.18 or recovery rate less than 1.0 PCr.Pi-1.min-1), and 13 of the 15 MH-negative patients had normal NMR results. Although neither NMR parameter alone was diagnostically reliable, an NMR test utilizing both parameters was quite accurate. The NMR test and contracture test demonstrated an overall agreement of 93% with a copositivity of 96% and conegativity of 87%. The sensitivity and specificity of the NMR test is estimated to be 98.8% +/- 11.8% and 95.3% +/- 20.3%, respectively. The role of 31P NMR in the diagnosis of MH susceptibility and possible mechanisms underlying the observations are discussed.

Adolescent↗