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Biomedical subjects

K G Warren

Publications and source records attributed to K G Warren.

At least 55 records · Page 3Linked to original sources

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↗

Detection of multiple strains of latent herpes simplex virus type 1 within individual human hosts.

One hundred and fifteen isolates of herpes simplex virus were recovered from parallel explant cultures of trigeminal and vagus ganglia and trigeminal nerve roots derived from 20 unselected human cadavers. Restriction enzyme patterns of strains recovered from 18 of 20 individuals could be differentiated from individual to individual, although all isolates from a single host were identical. Isolates from two individuals differed among themselves in the number and location of certain restriction enzyme sites.

Base Sequence↗

Evidence for cardiovascular autonomic nerve dysfunction in multiple sclerosis.

In 21 patients with multiple sclerosis and 20 healthy controls, the following tests of autonomic function were examined: (1) variation in heart rate during deep breathing, (2) the variations in heart rate and systolic blood pressure during a standardised Valsalva manoeuvre, (3) the changes in heart rate and systolic blood pressure during arm ergometry starting at 30 W with increments of 20 W every 3 min. In the control subjects the maximum variation in heart rate from inspiration to expiration was greater than 16 beat/min (range 17-43). In patients with multiple sclerosis, five had a maximum variation in heart rate of less than 13 beat/min which was considered as the lower limit of normal. The Valsalva ratio in the control subjects ranged from 1.33-3.24. Four patients had Valsalva ratios of less than 1.30. In patients with multiple sclerosis the heart rate and systolic blood pressure responses to exercise were attenuated significantly in four and seven subjects respectively. It is concluded that a significant number of patients with multiple sclerosis show evidence of autonomic dysfunction involving the cardiovascular system.

Adult↗

CSF myelin basic protein levels in acute optic neuritis and multiple sclerosis.

Normal CSF-MBP levels as determined by a RIA were less than 6.2 ng/ml CSF (mean 3.9). Eighty percent of patients with acute optic neuritis have CSF-MBP levels greater than 6.2 ng/ml (mean 7.6 ng/ml CSF). Five of 7 patients with acute internuclear ophthalmoplegia due to an initial exacerbation of demyelination have CSF-MBP levels above 6.2 ng/ml (mean 6.8 ng/ml). Fifty percent of MS patients with chronic progressive disease have CSF-MBP levels above 6.2 ng/ml (mean 6.7 ng/ml). MS patients experiencing monosymptomatic exacerbations show elevated CSF-MBP levels in 75% in 75% of cases (mean 8.2 ng/ml). MS patients experiencing polysymptomatic exacerbations show significantly higher levels of CSF-MBP (mean 22.3 ng/ml) than the patients with monosymptomatic exacerbations. Ninety-five percent of MS patients experiencing polysymptomatic exacerbations have elevated levels of CSF-MBP.

Acute Disease↗

Myelin basic protein: a component of circulating immune complexes in multiple sclerosis.

Myelin basic protein (MBP) is an antigenic component of circulating immune complexes (CIC) in patients with multiple sclerosis (MS). Immune complexes were isolated from the sera by adsorption to Raji cells and then acid eluted. Final identification of MBP from Raji eluates was done by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by MBP radioimmunoassay (RIA) of gel eluates and by an immunoblot technique.

Antigen-Antibody Complex↗

Variable restriction endonuclease sites of herpes simplex virus type 1 isolates from encephalitic, facial and genital lesions and ganglia.

The distribution of restriction endonuclease (RE) sites was compared for 84 herpes simplex virus type 1 (HSV-1) isolates obtained from the ganglia, facial lesions, genital lesions and from brain tissue from herpes encephalitis cases. The isolates came from Canada, the U.K., the U.S.A. and Japan. Out of a total of 224 sites identified, 87 were variable. Three of the 30 most variable sites were at significantly (P less than 0.05) different frequencies in groups of isolates from distinct anatomical sites of isolation; one of these, and a further two sites, were at significantly different frequencies in groups from distinct geographical origins. There are at least two inter-related linkage groups. However, most of the site combinations appear to be random. The variability of RE sites in contiguous genome segments, which include both non-coding and coding sequences, show a marked heterogeneity, indicating that some viral gene sequences are more variable than others. The three RE sites at different frequencies in viral groups from distinct anatomical sites of isolation are in two genome segments: map units 27 to 35 and 50 to 57. We infer from the observed associations with anatomical site of viral isolation that part of at least one of these segments may modulate viral virulence in man following infection.

Base Sequence↗

A comparative analysis of restriction enzyme digests of the DNA of herpes simplex virus isolated from genital and facial lesions.

The restriction endonuclease (RE) cleavage patterns of the DNA of herpes simplex virus (HSV) genital isolates from two geographically distinct groups and from one group of facial isolates were examined. Eleven of 21 genital isolates from females, 1 of 27 genital isolates from males and all 17 of the facial isolates were HSV type 1 (HSV-1). The groups of isolates of the same serotype could not be distinguished by significant differences in the frequency of variable restriction endonuclease sites or molecular weight of variable length fragments. Simultaneous consideration of two or more variable sites has disclosed some which are apparently correlated in the HSV-1 isolates, and which could provide a useful marker for phylogenetic relationships. However, most pairs showed no correlation, while certain sites appeared more closely correlated in the genital than in the facial isolates. All 39 HSV-2 isolates could be distinguished from each other on the basis of a combination of variable RE sites and variable length fragments. Bg/II RE sites appeared less variable than other RE sites.

DNA Restriction Enzymes↗

Effects of prolonged cultivation in the presence of acyclovir on recovery of latent herpes simplex virus from human trigeminal ganglia.

The continuous presence of acyclovir prevented the in vitro reactivation of latent herpes simplex virus from cultures of human trigeminal ganglia derived from 23 randomly selected cadavers. When acyclovir was withdrawn after 30 days, herpes simplex virus was recovered from 3 of 18 cases. Herpes simplex virus was recovered in 9 of 20 (45%) control cases.

Acyclovir↗

Interferon production by lymphocytes from multiple sclerosis and non-MS patients.

Peripheral blood lymphocytes from MS patients and non-MS patients were induced to produce interferon by incubation with canine distemper, mumps, Sendai, herpes simplex I, and two strains of measles viruses. Lymphocytes from MS patients produced as much pH 2 stable interferon as did those from non-MS patients in response to induction with any of these viruses. In addition, there were no significant differences in amounts of interferon produced by lymphocytes from MS patients in three different clinical stages of the disease.

Adult↗

Optic neuritis, diabetes mellitus and multiple sclerosis: a three-way association.

Patients with multiple sclerosis (MS) and a history of optic neuritis were compared with MS patients who had no such history for other illnesses among themselves and their family members. Significantly more of the patients with a history of optic neuritis than of those without (70% v. 41%) were diabetic or reported that at least one first- or second-degree relative had diabetes mellitus. No differences were found with regard to any other illnesses.

Adult↗

How multiple sclerosis is related to animal illness, stress and diabetes.

At the University of Alberta's multiple sclerosis research clinic 100 patients with multiple sclerosis were matched to control patients for age, sex, race and zone of residence before the age of 15 years. Case and control subjects were interviewed and information was collected by questionnaire on factors that might play a role in the development of multiple sclerosis. The only factors found to be significantly associated with the development of this disorder were a history of leisure time spent in physical activities before the onset of symptoms, exposure to animal illness -- specifically canine distemper -- and a history of severe or prolonged emotional stress. The study also confirmed a familial predisposition to multiple sclerosis and suggested a relation between the disorder and a personal or family history of diabetes mellitus.

Adolescent↗

Emotional stress and the development of multiple sclerosis: case-control evidence of a relationship.

One hundred multiple sclerosis (MS) patients were compared to hospital controls, for life stress prior to onset age in the MS patients and controls did not differ on: the happiness of their childhood environment; their pre-onset age reaction to life's problems (relaxed and taking things in stride/tense or easily upset); or on their tendency to seek professional help with an emotional problem. However significantly more MS patients than controls reported that they were under unusual stress in the 2 yr period prior to onset age; and the MS patients described a greater number of stressful life situations, or single events, than the controls.

Adult↗

Plasma exchange of malignant multiple sclerosis.

A 17-year old female with "malignant" multiple sclerosis died 45 weeks after the onset of the disease. Postmortem examination confirmed the clinical diagnosis of multiple sclerosis. After 30 weeks of rapid clinical progression, the patient was treated with two courses of plasma exchange therapy without immunosuppression. This form of therapy caused a drop in cerebrospinal fluid myelin basic protein levels in one instance, but not in another. Controlled clinical trials are required to determine whether plasma exchange therapy is of value in the management of patients with multiple sclerosis, and the monitoring of cerebrospinal fluid myelin basic protein, if elevated, may be one useful marker to follow as part of these studies.

Adolescent↗

Multiple sclerosis and diabetes mellitus: further evidence of a relationship.

One hundred multiple sclerosis (MS) patients were compared to healthy controls to determine the prevalence of diabetes mellitus in their families. Significantly, more MS patients than controls were diabetic or reported at least one first degree relative (parent, sibling, child) with diabetes. The relationship between MS and diabetes persisted when second degree relatives (grandparents, aunts and uncles) were taken into consideration. A greater percentage of MS patients with another MS relative were diabetic or reported a first degree relative with diabetes mellitus than MS patients without an MS relative. However the difference was not statistically significant. Nor was there a significant difference when percentages reporting either a first or a second degree relative with diabetes were compared.

Adult↗

Factors affecting recovery of latent herpes simplex virus from human trigeminal ganglia.

The rate of recovery of herpes simplex virus (HSV) from human trigeminal ganglia explant monolayers is affected by two factors: (1) time elapsed from the death of an individual to the establishment of in vitro culture of ganglia and (2) surface area onto which ganglia are explanted. Spontaneous reactivation of HSV from human trigeminal ganglia can be maximized when ganglia are obtained within 12 h of death and explanted into surface area of 250 cm2. Viruses isolated by explantation of human trigeminal ganglia were found to be uniformly HSV type 1 by restriction enzyme analysis.

Adolescent↗

Circulating immune complexes in multiple sclerosis: relation with disease activity.

Two hundred fifty-four MS patients were studied for circulating immune complexes (CIC) by three different assays: Raji-RIA, Clq-PEG, and Conglutinin-BA. Thirty-five percent of the sera were positive by one or more of these tests; Raji-RIA had the highest sensitivity (29.4%). Incidence of CIC in acute relapse, progressive, remission, and stable state of MS was 33.3%, 30.2%, 26.1%, and 23.1%, respectively, by Raji-RIA, compared with 7.75% and 8.82% among normal and neurologic controls. The incidence of CIC in neurologic controls differed significantly from both acute relapse and progressive disease, and almost significantly from patients in remission. There was no significant difference between patients with stable MS and neurologic controls, and there was no association of CIC with HLA-B7.

Adolescent↗