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Biomedical subjects

G Sherman

Publications and source records attributed to G Sherman.

14 recordsLinked to original sources

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

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

Running limb varus.

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Foot Deformities

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

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

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

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

Cutaneous basosquamous carcinoma of the head and neck: a comparative analysis.

Considerable debate has taken place concerning cutaneous basosquamous carcinomas. Some authors believe they are merely a variant of basal cell carcinoma, based on the apparent rare occurrence of metastases. This comparative study of 33 cases of basosquamous, 1,796 cases of basal cell, and 736 cases of squamous carcinomas arising in the head and neck demonstrates that the basosquamous lesion has the potential to recur and to metastasize, which is similar to squamous cell lesions. An aggressive primary treatment program is recommended.

Adolescent

Effect of subarachnoid morphine on the incidence of spinal headache.

BACKGROUND AND OBJECTIVES: The addition of fentanyl to hyperbaric local anesthetics has been shown to reduce the incidence of post dural puncture headache in the obstetric patient. This study was undertaken to evaluate the effects of subarachnoid morphine on the incidence of headache. METHODS: Eighty-two healthy patients undergoing cesarean delivery with spinal anesthesia were studied. All patients were hydrated with 1500 ml lactated Ringer's solution. Patients were randomly assigned to receive, in a double-blind fashion, 0.2 mg of either morphine (Group 1, n = 40) or saline (Group 2, n = 42) in 0.2 ml volume mixed with 0.75% bupivacaine in 8.25% dextrose plus 0.2 ml 1:1000 epinephrine. Spinal anesthesia was induced using a 25-gauge spinal needle at L3-4 interspace with the bevel, in most cases, parallel to the dural fibers. Patients were followed for three days to evaluate the incidence and severity of headache using a four-category rank scale (none, mild, moderate, severe). Data were analyzed for statistical significance using Student's t-test or chi-square test as appropriate. A p value less than 0.05 was considered significant. Results. The incidence of post dural puncture headache did not differ significantly between groups. Eight patients in Group 1 versus nine patients in Group 2 developed headache (p greater than 0.05). Similarly, the use of blood patch or intravenous caffeine sodium benzoate to treat the headache did not differ significantly between groups. CONCLUSION: It is concluded from our study that subarachnoid morphine did not decrease the incidence of post dural puncture headache in the obstetric patient.

Adult

Epidural butorphanol augments lidocaine sensory anesthesia during labor.

To determine the efficacy and safety of epidural butorphanol combined with lidocaine, 50 healthy parturients were studied during labor and delivery. All patients received a test dose of 3 ml 1.5% lidocaine with 1:200,000 epinephrine. Patients were then randomly assigned to receive 7 ml of one of two epidural regimens in a double-blind fashion: Group 1 patients received 1.5% lidocaine plus 1 mg butorphanol plus 1:300,000 epinephrine; Group 2 patients received 1.5% lidocaine plus 1:300,000 epinephrine. Each group consisted of 25 patients. The study ended at the time of redosing. All subsequent epidural injections were made with one bolus of plain 0.25% bupivacaine followed by continuous infusion of 0.125% bupivacaine. Duration of anesthesia was significantly longer for Group 1 compared to Group 2 (p less than 0.01), 124 +/- 8 minutes versus 99 +/- 6 minutes (mean +/- SEM). There were no difference between groups in duration of first and second stages of labor, method of delivery or neonatal outcome. Umbilical cord acid-base status and neurologic adaptive capacity scores did not differ significantly between the two groups. The authors conclude that adding small doses of butorphanol to epidural lidocaine during labor is effective and safe.

Adult