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Biomedical subjects

G Sherman

Publications and source records attributed to G Sherman.

At least 37 records · Page 2Linked to original sources
PubMed1992

The UL8 subunit of the herpes simplex virus helicase-primase complex is required for efficient primer utilization.

The herpes simplex virus (HSV) type 1 helicase-primase is a three-protein complex, consisting of a 1:1:1 association of UL5, UL8, and UL52 gene products (J.J. Crute, T. Tsurumi, L. Zhu, S. K. Weller, P. D. Olivo, M. D. Challberg, E. S. Mocarski, and I. R. Lehman, Proc. Natl. Acad. Sci. USA 86:2186-2189, 1989). We have purified this complex, as well as a subcomplex consisting of UL5 and UL52 proteins, from insect cells infected with baculovirus recombinants expressing the appropriate gene products. In confirmation of previous reports, we find that whereas UL5 alone has greatly reduced DNA-dependent ATPase activity, the UL5/UL52 subcomplex retains the activities characteristic of the heterotrimer: DNA-dependent ATPase activity, DNA helicase activity, and the ability to prime DNA synthesis on a poly(dT) template. We also found that the primers made by the subcomplex are equal in length to those synthesized by the UL5/UL8/UL52 complex. In an effort to uncover a role for UL8 in HSV DNA replication, we have developed a model system for lagging-strand synthesis in which the primase activity of the helicase-primase complex is coupled to the activity of the HSV DNA polymerase on ICP8-coated single-stranded M13 DNA. Using this assay, we found that the UL8 subunit of the helicase-primase is critical for the efficient utilization of primers; in the absence of UL8, we detected essentially no elongation of primers despite the fact that the rate of primer synthesis on the same template is undiminished. Reconstitution of lagging-strand synthesis in the presence of UL5/UL52 was achieved by the addition of partially purified UL8. Essentially identical results were obtained when Escherichia coli DNA polymerase I was substituted for the HSV polymerase/UL42 complex. On the basis of these findings, we propose that UL8 acts to increase the efficiency of primer utilization by stabilizing the association between nascent oligoribonucleotide primers and template DNA.

Adenosine Triphosphatases↗
PubMed1991

Body awareness and medical care utilization among older adults in an HMO.

This study investigated the association between the disposition of body awareness and medical care utilization among older adult members of a health maintenance organization (HMO). Results indicated that higher levels of body awareness are associated significantly with longitudinal increases in the volume of patient-initiated illness visits to the HMO, and with a greater likelihood of patient-initiated contact with the hospital emergency room, controlling for prior utilization, self-reported health status, and other factors. In contrast, body awareness was not associated significantly with longitudinal changes in physician-initiated follow-up visits, internal referrals, external referrals, or hospital inpatient days. Other findings indicated that higher levels of patient-initiated utilization were associated with greater physician-initiated utilization, controlling for prior utilization. These results illustrate how patient-initiated utilization may influence subsequent physician-initiated utilization.

Aged↗
PubMed1991

Running limb varus.

Explore the source record for details and available documents.

Foot Deformities↗
PubMed1988

Chemicals, birth defects and stillbirths in New Brunswick: associations with agricultural activity.

We describe a series of investigations that were conducted in support of the Task Force on Chemicals in the Environment and Human Reproductive Problems in New Brunswick. Geographic and temporal analyses and case-control studies, with the use of vital statistics, hospital records, the Canadian Congenital Anomalies Surveillance System and chemical databases, revealed no association between pesticides used in forestry and reproductive problems. Evidence of an association between the potential exposure to agricultural chemicals and three major anomalies combined as well as spina bifida without hydrocephalus was found. More plausible was an association between stillbirths and such exposure during the second trimester of pregnancy. This finding, along with the cyclic patterns of stillbirth in the agricultural Saint John River basin and the somewhat higher stillbirth rates in New Brunswick than in adjacent provinces or in Canada as a whole, suggests that further attention should focus on possible associations between agricultural activity and stillbirths.

Abnormalities, Drug-Induced↗
PubMed1988

Characterization of intranuclear capsids made by ts morphogenic mutants of HSV-1.

We have characterized capsids made by seven temperature-sensitive (ts) mutants of HSV-1 previously shown to be defective in viral DNA processing and packaging at the nonpermissive temperature (NPT). The empty capsids isolated from mutant-infected cells at the NPT were devoid of DNA, cosedimented in sucrose with wt B capsids, and contained the same structural proteins found in wt B capsids (W. Gibson and B. Roizman (1972). J. Virol. 10, 1044-1052). The presence of VP22a in empty capsids suggests that the processing of this protein from higher-molecular-weight precursors and its association with capsids is required, but not sufficient, for DNA encapsidation. Mutants made no detectable A capsids at the NPT, but did so at the permissive temperature (PT), suggesting that A particles are generated during or subsequent to, rather than prior to, encapsidation. In temperature-shift experiments, it was demonstrated that capsids of one of the mutants, F18, made at the NPT did not participate in DNA encapsidation when cells were subsequently shifted to the PT. Only those capsids made after temperature shift to the PT acquired viral DNA, implying that the ts mutation in F18 may lie in a gene coding for a structural protein, or in a protein involved in the processing of viral DNA.

Animals↗
PubMed1987

DNA processing in temperature-sensitive morphogenic mutants of HSV-1.

The anatomy of DNA synthesized by five HSV-1 mutants previously shown to accumulate predominantly empty capsids at the nonpermissive temperature (NPT) was analyzed with Bg/II restriction digestion. At the NPT, all five generated DNA lacking termini, indicating that in the absence of packaging, viral DNA is not processed to unit length. One mutant, F18, was able to process DNA made at the NPT to unit length molecules during a 6-hr period after shift to the permissive temperature. The appearance of unit length molecules correlated with the appearance of staphylococcal nuclease-resistant F18 DNA.

Capsid↗
PubMed1984

Selectivity of cholestyramine treatment on hepatic mixed function oxidase activity.

The possibility that oral cholestyramine treatment might indirectly increase hepatic drug oxidations was investigated in rats using pentobarbital, antipyrine, zoxazolamine, and aminopyrine as probes of the hepatic mixed function oxidase system and in humans using amobarbital and antipyrine as probes. Cholestyramine pretreatment of rats for 5 days (87.5 mg/kg twice daily by stomach tube) shortened pentobarbital sleep times, decreased antipyrine-induced hypothermia, but did not influence either zoxazolamine paralysis times or the in vitro N-demethylation of aminopyrine. Neither pentobarbital nor antipyrine pharmacokinetics in rats were affected by the cholestyramine pretreatment. Similarly, in two-way crossover studies with human subjects, a 5-day oral cholestyramine pretreatment (4 g 3 times daily) had no demonstrable effect on the pharmacokinetics of single doses of amobarbital (200 mg i.v.) or antipyrine (500 mg per os). After cholestyramine pretreatment, a trend toward diminished CNS depression produced by amobarbital was observed, but the effect was not statistically significant. The results suggest that hepatic mixed function oxidases in rats for which aminopyrine, antipyrine, pentobarbital, and zoxazolamine are substrates and that hepatic mixed function oxidases in humans for which amobarbital and antipyrine are substrates are not significantly affected by cholestyramine pretreatment.

Adult↗
PubMed1981

Discriminative response control by naloxone in morphine pretreated rats.

In an operant procedure using a lever press response 12 male, hooded rats were trained to discriminate 1.25 mg/kg naloxone from a saline injection. On certain days, according to a counterbalanced training schedule, naloxone was administered 8 h after 40 mg/kg morphine and 10 min prior to a trail in which food was available on an FR10 schedule from one of two levers in a dual lever operant chamber. On other days saline was administered 10 min prior to a trial in which food was made available by pressing the other lever. After criterion performance for acquisition of the discrimination had been reached, tests were carried out to determine its nature. Discrimination of naloxone was dose-dependent and was significantly diminished when naloxone was administered 36 h after morphine. Partial generalization of cyclazocine with naloxone was observed. Spontaneous withdrawal from morphine, tested during trials preceeded by an injection of saline instead of naloxone at various time intervals after morphine, did not generalize with the naloxone discriminative stimulus.

Animals↗
PubMed1980

Thick filament size changes in contraction of human muscles.

Measurements done on electron micrographs shows that in myofibres with sarcomeres contracted to below 2.1 micron, proportional shortening of the A bands occurs. In muscles from patients with idiopathic scoliosis very short A bands are especially prominent.

Cytoskeleton↗
PubMed1979

Primary malignant lymphoma of the small intestine in Israel. Changing incidence with time.

One hundred and eighty-one cases of primary small intestinal lymphoma were diagnosed in residents of Israel--145 Jews and 36 Arabs--during a 16-year period, 1960--75. The male:female ratio was 1.8:1. Incidence rates were higher in children, the middle-aged and the elderly than in teenagers or young adults. Crude and age-adjusted incidence rates were higher in Arabs than in Jews. The pattern among the subgroups of the Jewish population varied with age. In young adults of both sexes the rates were much higher among Jews born in North Africa or Asia than among those born in Europe or Israel. In elderly males, however, the rates were almost twice as high in European-born Jews than among those born in North Africa or Asia. The mean annual incidence of primary small intestinal lymphoma fell from 4.8 per million during 1960--67 to 3.6 per million during 1968--75. This was due to a marked fall in the rates in children and young adults, whereas the rates in those aged 40 years or more rose with time. The pattern of the change with time suggests that environmental conditions are an important factor in the causation of primary intestinal lymphoma in young adults.

Adolescent↗