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Biomedical subjects

M Silverman

Publications and source records attributed to M Silverman.

At least 379 records · Page 21Linked to original sources
PubMed1979

Phase variation in Salmonella: genetic analysis of a recombinational switch.

The alternative expression of Salmonella genes H1 and H2, which specify different flagellar antigens, results in the oscillation of phenotype known as phase variation. This alternation is controlled by the inversion of an 800-base-pair sequence of DNA adjacent to, or including part of, the H2 gene. The invertable region was presumed to regulate the function of a promoter and to include specific sites at which a recombinational event, resulting in the inversion, could occur. Here we report genetic manipulations of hybrid lambda phage carrying the H2 gene that were used to define the H2 promoter region and the recombinational sites. The H2 gene fragment was inserted on a hybrid lambda phage next to the cheW gene, which lacked a promoter element. In the resulting fusion, cheW gene activity was restored, the expression of the H2 and cheW genes was controlled coordinately by the inversion, and the polarity of transcription and location of the H2 gene could be determined. Evidence from this type of gene fusion suggested that the H2 gene promoter is included in the inversion region. Hybrid H2 phage were constructed that contained substitutions for regions of the H2 gene. In contrast to hybrid lambda containing the H2 gene, which alternate between "on" and "off" states, several substituted lambdaH2 were fixed in the "on" state. A site necessary for the recombinational event must have been removed in these fixed lambdaH2.

Bacterial Proteins↗
PubMed1979

Flagellar-phase variation: isolation of the rh1 gene.

In Salmonella, expression of flagellar antigen alternates between two serotypes (phases) encoded by two genes, H1 and H2. The mechanism which controls the alternative expression of the H1 and H2 genes was examined by cloning these genes and the genetic elements which control their activity on hybrid vehicles in Escherichia coli. H2 gene activity was shown to be controlled by a recombinational switch located adjacent to the H2 gene. Activity of the H1 gene is thought to be repressed, when the H2 gene is expressed, by the product of another gene, rh1 (repressor of H1), which is controlled coordinately with the H2 gene. In this report, we describe the construction of hybrid lambda vehicles which contain, in addition to the H2 gene, a genetic activity corresponding to rh1. Variation of flagellar antigens analogous to that observed in Salmonella was observed when E. Coli strains were transduced with the hybrid lambda. By using the lambdaH2rh1 hybrid to program protein synthesis in UV-irradiated cells, the synthesis of a polypeptide was correlated with rh1 gene product activity. We conclude that the H2 region consists of two cotranscribed genes, H2 and rh1. The expression of both gene products is regulated by the same recombinational event.

Bacterial Proteins↗
PubMed1979

New technique for servo-control of arterial oxygen tension in preterm infants.

Equipment has been developed for the servo-control of arterial oxygen tension in sick, newborn babies. Using an indwelling umbilical arterial oxygen electrode as sensor, the equipment successfully regulated the administration of oxygen to 12 newborn babies with respiratory distress syndrome, significantly improving the stability of arterial oxygen tension and lessening the duration of episodes of hypoxia and hyperoxia.

Arteries↗
PubMed1979

Running, walking, and hyperventilation causing asthma in children.

To examine further the relation between type of exercise, workload, ventilation, and exercise-induced asthma, we compared treadmill walking with treadmill running and treadmill running with isocapnic hyperventilation in separate studies in children and adolescents. Inspired air conditions were identical during each pair of tests. Walking and running with similar minute ventilation and oxygen consumption were followed by similar falls in peak expiratory flow rate as were running and hyperventilation with similar minute ventilation and end-tidal carbon dioxide tension. This study supports the concept that hyperventilation is a central mechanism in exercise-induced asthma.

Adolescent↗
PubMed1979

Vitamin B12 uptake in dog kidney: its use as an extracellular reference marker.

The renal handling of [3H]cyanocobalamin has been investigated in dogs in vivo using the pulse injection multiple-indicator dilution technique. Simultaneous renal vein and urine outflow curves were obtained for [3H]cyanocobalamin relative to T-1824-albumin (plasma reference) and creatinine (extracellular reference). The renal vein recovery of [3H]cyanocobalamin relative to creatinine was significantly less than unity and increased with increasing intraarterial dose. This indicates a saturable postglomerular uptake mechanism. The urine recovery of [3H]cyanocobalamin relative to simultaneously filtered creatinine is also less than unity and increases with increasing intra-arterial doses. This indicates a saturable interaction at the luminal surface of the nephron. Saturation interaction at the luminal surface of the nephron. Saturation of postglomerular and luminal interactions can also be achieved by systemic preloading with unlabeled vitamin B12. After saturation the renal vein and urine recoveries for [3H]cyanocobalamin and creatinine become equal. However, significant differences can be observed between their renal vein mean transit times, depending on experimental conditions. During hydropenia [3H]cyanocobalamin behaves as a true extracellular marker and emerges in renal vein and urine outflows, superimposing on creatinine. During mannitol diuresis vitamin B12 still behaves as a glomerular marker, but its renal vein mean transit time is now significantly less than that of creatinine and its calculated postglomerular volume of distribution is reduced by approximately 15% of the available interstitial space.

Animals↗
PubMed1979

Cell volume decrease during Friend leukemia cell differentiation.

Friend leukemia cells (GM86, clone 745) were induced to differentiate with dimethyl sulfoxide or butyric acid. The kinetics of induction were measured by cell growth, cell volume distributions, and [3H]thymidine incorporation. From the volume distributions, it was found that the rate of induction was both agent sensitive and concentration dependent. The changes in volume distributions occurred approximately 4 hr earlier with dimethyl sulfoxide induction relative to butyric acid induction. However, the changes with the butyric acid induction were more dependent on concentration. A decrease in labeling indices during the 12- to 20-hr time period was correlated to a decrease in mean cell volume and an increase in the proportion of G1 cells. After the 20-hr time period of induction, an increase in labeling indices and in the percentage of large cells was observed. The data suggest that a transient block of cells in G1 occurred between 12 to 20 hr, and that the early differentiation involved a volume decrease which was related to a redistribution of cell cycle stages. The study was also shown that the changes of cell volume are a rapid monitor to determine the early events of the differentiation process.

Animals↗
PubMed1979

Allergy in cystic fibrosis.

Forty-four patients with cystic fibrosis, sixty-seven parents, and thirty-nine controls were compared with regard to their immediate cutaneous hypersensitivity, total and specific serum IgE and serum IgG4 concentrations. The patients had increased prick test reactions and specific IgE to Aspergillus fumigatus. The development of reactions to A. fumigatus correlated with the severity of the disease. There were no other significant differences when serum total IgE, specific IgE and IgG4 concentrations or skin test reactivity were compared in the patients, parents and controls.

Adult↗
PubMed1978

Sugar uptake into brush border vesicles from dog kidney. II. Kinetics.

The kinetics of D-glucose transport over the concentration range 0.07--20 mM have been investigated in a vesiculated membrane preparation from dog kidney cortex. 1. A sodium-dependent and a sodium-independent component of D-glucose uptake are observed. The sodium-dependent component is phlorizin sensitive (KI approximately 0.6 micron) and electrogenic. 2. The sodium-dependent component of D-glucose uptake yields non-linear Eadie-Hofstee plots consistent with the presence of high (GH) and low (GL) affinity sites (KH approximately 0.2 mM, KL approximately 4.5 mM, VL/VH approximately 7 at pH 7.4, 25 degrees C, 100 mM NaC1 gradient). Alternative explanations are cooperative effects of non-Michaelis-Menten kinetics. 3. The initial uptake of D-glucose increases as the intravesicular membrane potential become more negative but the numerical values of KH and KL show little, if any, change. 4. alpha-Methyl-D-glucoside transport is also sodium dependent and phlorizin sensitive (KI approximately 1.9 micron). 5. In contrast to the results for D-glucose, the sodium-dependent component of alpha-methyl-D-glucoside uptake exhibits a nearly linear Eadie-Hofstee plot consistent with a single carrier site with Km approximately 1.9 mM and Vmax approximately 27 nmol/min per mg protein at pH 7.4, 25 degrees C, 100 mM NaCl gradient. 6. The kinetics of D-glucose transport in newborn dog kidney are similar to those in the adult except that the low affinity (GL) system appears to be less well developed.

Animals↗
PubMed1978

Randomized phase II clinical trial of adriamycin, methotrexate, and actinomycin-D in advanced measurable pancreatic carcinoma: a Gastrointestinal Tumor Study Group Report.

Sixty-six patients with advanced pancreatic carcinoma were randomized to receive single agent chemotherapy with either adriamycin, methotrexate, or actinomycin-D using conventional dose, route and schedule of administration. All patients had measurable lesions which were used to objective assessment of response. For adriamycin, 2 of 25 patients (8%) evidenced a partial response (2 of 15 (13%) previously untreated patients). One of 25 patients treated with methotrexate and one of 28 received actinomycin-D responded. The duration of responses ranged from 43-64 days for those patients with no chemotherapy prior to study entry. The median survival of patients who received adriamycin as initial treatment was 12 weeks compared to 8 weeks for methotrexate and 6 weeks for actinomycin-D therapy.

Adult↗
PubMed1978

Identification of the structural gene for the hook subunit protein of Escherichia coli flagella.

Previous studies showed that the structural gene for the flagellar hook subunit protein (molecular weight 42,000) was one of a group of flagellar genes located on the Escherichia coli genome near pyrC. Several lines of evidence indicate that the flaK gene is the structural gene for the hook subunit protein. Fla+ strains that were insensitive to chi infection could be isolated as revertants of an FlaK- amber mutant strain but from no other Fla- strain. The hook subunit proteins isolated from such chi-sensitive revertants of the FlaK- strain were shown to be antigenically and electrophoretically different from the hook protein isolated from the wild-type strain. Thus, reversion of a mutation in the flaK gene resulted in alteration of the structure of the hook protein. Furthermore, in programming experiments with hybrid lambda containing flagellar genes, lambdafla with flaK genetic activity programmed the synthesis of a 42,000-molecular weight protein, whereas lambdafla without flaK genetic activity did not.

Bacterial Proteins↗
PubMed1978

Genes for the hook-basal body proteins of the flagellar apparatus in Escherichia coli.

Of the more than 30 genes required for flagellar function, 6 are located between pyrC and ptsG on the Escherichia coli genetic man. This cluster of genes is called flagellar region I. Four-point transductional crosses were used to establish the position and order of the region I flagellar genes with respect to the outside markers ptsG and pyrC. Bacteriophage lambda-E. coli hybrids that contained most of the genes necessary for flagellar formation were constructed. The properties of specific hybrids that carried the region I fla genes were examined by genetic complementation and by measuring the capacity of the hybrids to direct the synthesis of specific polypeptides. The results of these tests with lambda hybrids and with a series of deletion mutations derived from the lambda hybrids demonstrated the existence of at least six flagellar-specific cistrons. These directed the synthesis of polypeptides with the following apparent molecular weights: flaV, 11,000; flaK, 42,000; flaL, 30,000 and 27,000; flaM, 38,000; flS, 60,000; and flaT, 35,000. Plasmid ColE1-E. coli hybrids with region I flagellar genes were also used to program the synthesis of polypeptides in minicell-producing strains. The polypeptides synthesized in these experiments were identical to polypeptides of the hook-basal body structure and helped to confirm the assignment of genes to specific polypeptides. The synthesis of all of these polypeptides was regulated by the same mechanism that regulates the synthesis of other flagellar-related structural components.

Bacterial Proteins↗
PubMed1978

Cystic fibrosis, atopy, and airways lability.

In a survey of cystic fibrosis (CF) in the Avon area, 48 children with CF from 40 families together with 71 of their parents were studied by spirometry, exercise tests, and pinch tests. A control group of 42 young adults was similarly tested; control data for children were taken from previously published work. The prevalence of atopy (any positive prick test) in children with CF was 48%. Sensitivity to grass pollens and house dust mite was no more common in these children (29%) than in a normal population (34%). Hypersensitivity to Aspergillus fumigatus was found in 35% of children with CF and was associated with severe lung disease. The parents had a normal pattern and prevalence of atopy. Exercise-induced airways obstruction was present in only 22% of children with CF; its association with severe lung disease rendered interpretation difficult. The parents had a normal response to exercise. Both hypersensitivity to A. fumigatus and exercise-induced airways lability had the features of acquired characteristics. There was nothing in the present study to support the hypothesis that the possession of a CF gene predisposed to atopy.

Adult↗