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Biomedical subjects

S M Brown

Publications and source records attributed to S M Brown.

At least 163 records · Page 9Linked to original sources

Herpes simplex virus in the cornea; an ultrastructural study on viral reactivation.

Infectious HSV was isolated from the corneal disc of a patient with chronic stromal keratitis. A morphological study was performed on the corneal tissue after detection of HSV by organ culture. The characteristic features of HSV replication were observed within the keratocytes, including formation of nucleocapsid structures; encapsidation of viral DNA; envelopment and egress of virons. The following effects of viral replication upon cells were seen, margination and condensation of nuclear chromatin, formation of aberrant viral structures, re-duplication of nuclear membranes and cellular destruction. This study demonstrates that HSV replication occurs within keratocytes. HSV replication is an important step in the evolution of disciform herpetic keratitis.

Adult↗

Isolation and characterization of deletion mutants of herpes simplex virus type 2 (strain HG52).

We provide evidence that: (i) two variants lacking the XbaI site at map coordinate 0.7 have been selected following XbaI treatment of the DNA of herpes simplex virus type 2 strain HG52; (ii) one of these mutants had lost the 0.7 restriction site due to a deletion of approximately 150 base pairs and in the other the site loss was due to a similar sized sequence insertion; (iii) following XbaI treatment, four variants with deletions ranging in size from 1.5 kb (in both TRL and IRL) to 9 kb in IRL were isolated; (iv) substantial deletions in the long terminal repeat regions of HG52 are present with a frequency of 24% of genomes in the elite stock, a variant with a 3.75 kb deletion in IRL making up 10% and one with a 1.5 kb deletion in both IRL and TRL making up 14%; (v) two of the variants isolated after XbaI treatment of viral DNA were identical to the deletion prototype within the elite stock, suggesting that these variants were not generated as a result of XbaI treatment but pre-existed in the viral DNA pool; (vi) the deletion variants were stably maintained during routine stock propagation, were viable and could be propagated as cloned populations; (vii) the deletions did not have a marked deleterious effect on the one-step growth kinetics of the virus.

Autoradiography↗

Recovery of herpes simplex virus genetic information from human trigeminal ganglion cells following superinfection with herpes simplex virus type 2 temperature-sensitive mutants.

Explant cultures of human trigeminal ganglia were derived from 36 individuals. Those cultures which failed to release herpes simplex virus (HSV) spontaneously were superinfected at various times after establishment in vitro with a range of HSV-2 temperature-sensitive (ts) mutants. Eight cultures from six individuals contained HSV-specific genetic information which could be detected or rescued following superinfection. Restriction enzyme analysis of ts+ virus recovered from the ganglia of two individuals following superinfection was identical to that of endogenous HSV-1 spontaneously released from parallel cultures. Retrieval of ts+ virus by this technique suggests products of the superinfecting virus activated expression of whole genomes or that spontaneous virus expression occurred unrelated to the act of superinfection.

Gene Expression Regulation↗

Isolation of restriction endonuclease site deletion mutants of herpes simplex virus.

We provide evidence that (i) variants lacking individual herpes simplex virus type 1 (HSV-1) XbaI sites can be selected following extensive XbaI treatment of the viral DNA and can be recombined to produce HSV-1 variants lacking two of the four sites normally found, (ii) all XbaI sites can be removed from a viable intertypic recombinant HSV genome, (iii) following XbaI treatment, different mutants with deletions (0.15 to 8.8 kb) in the long repeat ( TRL or IRL ) and long unique regions can be readily isolated, as well as mutants with novel XbaI sites, (iv) several mutants with deletions in one of the repeats ( TRL or IRL ) have a measurable growth disadvantage in tissue culture.

Binding Sites↗

Attachment of tail fibers in bacteriophage T4 assembly. Identification of the baseplate protein to which tail fibers attach.

A phage-neutralizing rabbit antiserum collected after immunization with tail-fiberless bacteriophage T4 particles was adsorbed with complete T4 phage. The resulting adsorbed serum inhibited tail fiber attachment in vitro. To identify the antigens against which this inhibitory activity was directed, blocking experiments were carried out with the adsorbed serum. Isolated complete baseplates and mutant-infected-cell extracts lacking known baseplate gene products but containing gene 9 product showed similar high levels of blocking activity. By contrast, both tail-fiberless particles lacking gene 9 product and infected-cell extracts made with gene 9 mutants showed 30-fold to 100-fold lower blocking activity. These results strongly support the conclusion that gene 9 product is the baseplate protein to which tail fibers attach.

Antigens, Viral↗

Lung cancer and occupation in Alameda County: a death certificate case-control study.

A case-control comparison of lung cancer deaths versus deaths from all other cancers occurring in Alameda County, California, between 1958 and 1962 was conducted to investigate possible associations between lung cancer and occupation. Age-adjusted, sex-specific analyses indicated that a history of work in certain industries and occupations was associated with an increased risk of lung cancer. Among males, a significant positive association was found for glass, metal, furniture, professional and photographic equipment, rubber, leather and plastic manufacturing; water and air transportation; auto repair services; and construction. Specific occupations associated with a significant positive risk for males were: electricians, aircraft mechanics, painters, plasterers, machine operators, construction workers, bus and truck drivers, and guards and nightwatchmen. Among females, beauticians had a significantly high risk associated with lung cancer. These results were consistent with other studies of lung cancer related to occupation.

Adult↗

Differential susceptibility of human neural cell types in culture to infection with herpes simplex virus.

The ability of herpes simplex virus (HSV)-1 Glasgow (strain 17), HSV-2 (strain HG52), temperature sensitive mutants and a thymidine kinase negative mutant of Glasgow strain 17 to produce a cytopathic effect and induce viral antigen expression in primary and passaged human fetal brain cells was studied. No difference was detected between the behaviour of HSV-1 and HSV-2. Cell-type-specific markers and indirect immunofluorescence were used to define unambiguously the type of individual cells in culture. Cells characterized as astrocytes were present in passaged cultures. Neurons were only seen in primary cultures and were markedly nonpermissive for herpes simplex virus as defined by both cytopathic effect and antigen expression when compared with the other cell types. These techniques and observations are seen to have potential significance for a variety of clinical neurological and neurobiological studies.

Animals↗

Screening procedure for uric acid as indicator of infestation in spices.

Uric acid levels in selected spice products were determined by using a glucose analyzer, modified and calibrated for uric acid. In the method, uricase is used to decompose the uric acid; the reaction is monitored with an oxygen-sensitive electrode. Uric acid levels correlated with infestation as determined by AOAC methods.

Condiments↗

Bromocriptine suppresses ACTH secretion from human pituitary tumour cells in culture by a dopaminergic mechanism.

Bromocriptine (0.13-13 microM) significantly inhibited ACTH secretion in a dose-dependent manner when added to cell cultures of a human corticotrophic adenoma for 24 h. Haloperidol (13 microM), but not serotonin (13 microM), blocked this inhibition but had no significant effect when added alone. In addition, dopamine (10 microM) reduced ACTH secretion during a 4-h incubation, whereas serotonin (0.01-10 microM) was ineffective. An ectopic ACTH secreting lung carcinoid was non-responsive to doses of bromocriptine up to 13 microM. These results demonstrate a direct suppressive action of bromocriptine on a human pituitary corticotrophic adenoma through dopaminergic rather than serotoninergic mechanisms.

Adenoma↗

Terbutaline sulfate in the prevention of recurrence of premature labor.

Forty-six patients in premature labor were initially successfully treated with ethanol infusion. Twenty-three of these patients were then given prolonged oral terbutaline sulfate therapy until 38 weeks' gestation, and the remaining 23 patients were given placebo. The treated group gained significantly more time in gestation than the placebo group (P < .05), although the placebo group started with a higher Bishop score. In addition, idiopathic respiratory distress syndrome was seen significantly less often in the treated group. There was no perinatal mortality in either group.

Clinical Trials as Topic↗

Variations in herpes simplex virus isolated from human ganglia and a study of clonal variation in HSV-1.

Growth of human sensory ganglia in culture has led to the reactivation of herpes simplex virus from over 50% of cases studied. Infected cell polypeptide and restriction enzyme analysis has led to the conclusion that each individual has one unique latent strain of HSV-1 that can be present in more than one ganglion in the body. Analysis of 91 isolates has shown that the long region of the genome is variable in terms of DNA restriction sites, DNA sequences, and in coding for the majority of variable polypeptides. The short region is stable with only polypeptides Vmw 21 and 22, restriction sites HindIII-(M-N) and BglII-(G-H) and the DNA sequence BamHI-1' having been found to vary. The insertion and deletion of small DNA sequences at specific locations allows individual reactivation events to be distinguished. Detection of information able to complement and produce ts+ virus on superinfection of otherwise negative ganglia with ts mutants, has led to the conclusion that ganglion cells may harbor herpes virus-related information that is only detectable by use of such genetic probes.

Base Sequence↗

The use of epidemiologic data in the assessment of cancer risk.

Epidemiologic data can be extremely important in arriving at quantitative estimates of human cancer risk, expressed either as (a) attributable risk, or (b) relative risk. While case-control studies have a low cost/benefit ratio, cohort studies are more likely to yield data relating risk to amount of exposure, and to allow precise calculation of risk. However, cohort studies are long, expensive, and difficult to administer. Attrition and resultant unrepresentative composition can be major problems. Cohorts should be followed to extinction to permit accurate calculation of risk, which must take into account prolonged latency periods, competing risks, and the likelihood of increasing risk with time (or age). In view of certain limitations in epidemiologic and virologic methods, critical re-evaluation of the viral and oncogene theories are called for. The use of animal data for assessing human cancer risk requires further investigation of the assumptions and facts supporting two kinds of extrapolation: That from high to low dose carcinogen exposure, and cross-species extrapolation (i.e., from experimental animals to man). Large pieces of these two approaches rest on testable hypotheses which deserve further attention.

Costs and Cost Analysis↗