Search PubMed⌕ Search

Biomedical subjects

C Winter

Publications and source records attributed to C Winter.

At least 109 records · Page 6Linked to original sources

Antigenic variation in the hemagglutinin-neuraminidase protein of human parainfluenza type 3 virus.

Sixteen monoclonal antibodies directed to the hemagglutinin-neuraminidase (HN) protein of a 1957 isolate of parainfluenza type 3 virus (PIV3) were produced and used to examine antigenic variation in clinical strains. Analysis of hemagglutination-inhibition reactivity patterns of antigenic variants selected in vitro in the presence of monoclonal antibodies indicated that there were a minimum of six distinct epitopes detectable on the HN molecule. Competitive-binding assays indicated that these epitopes were located in two topologically nonoverlapping antigenic sites. An additional four epitopes were detected when 37 PIV3 clinical strains isolated over a period of 26 years in three geographic regions were tested for reactivity with the antibodies. Of the 10 unique epitopes defined by our monoclonal antibodies, 5 did not undergo detectable antigenic variation in any of the 37 strains examined. These results were expected since PIV3 viruses have been characterized as being antigenically monotypic. In contrast, antigenic variation was detected in the remaining five epitopes. This variation was not characterized by the accumulation of antigenic alterations with time (as for influenza A viruses), but appeared to represent genetic heterogeneity within the PIV3 population.

Animals↗

A double-blind study of oral acyclovir for suppression of recurrences of genital herpes simplex virus infection.

Patients with frequently recurring genital herpes were enrolled in a double-blind placebo-controlled trial comparing 200-mg acyclovir capsules, given five or two times daily, with placebo. Of 47 placebo recipients, 44 (94 per cent) had recurrences during the 120-day treatment period, compared with 13 (29 per cent) of 45 patients treated with acyclovir five times daily and 18 of 51 (35 per cent) treated with acyclovir twice daily (P less than 0.001 for each regimen compared with placebo). The median time to the first clinical recurrence was 18 days in placebo recipients, compared with over 120 days in both acyclovir-treated groups (P less than 0.001 for both groups compared with placebo). The mean monthly recurrence rate during the medication period was 0.86 in placebo recipients, compared with 0.13 in patients treated with acyclovir five times daily and 0.14 in patients treated with acyclovir twice daily (P less than 0.001 for both groups compared with placebo). While receiving therapy, 86 of 96 acyclovir-treated patients had over a 50 per cent reduction in their pretreatment recurrence rate. Breakthrough recurrences in acyclovir recipients were of shorter duration and associated with a lower frequency of viral shedding than recurrences in placebo recipients. After medication was discontinued, the subsequent recurrence rate returned to pretreatment frequencies. Daily oral acyclovir was well tolerated. We conclude that oral acyclovir given for four months markedly reduces but does not completely prevent recurrences of genital herpes and does not influence the long-term natural history of the disease.

Acyclovir↗

The effects of long-term physical training in patients with coronary heart disease.

A previous trial was completed in 24 patients with coronary heart disease, randomly assigned to a group who undertook a 6-month exercise training programme (5BX/XBX) and a control (no training) group. It was shown that the patients in the training group were able to achieve during exercise a higher heart rate at ST segment depression of 0.1 mV (HR/ST threshold) and that the patients in the control group showed a reduction in the threshold as well as symptomatic deterioration; the results indicated that the training programme had resulted in a reduction in the severity of myocardial ischaemia. In the present trial 9 patients of the previous training group were followed up to examine the effect of long-term maintenance training (up to 4.5 years). The same methods were used to examine the effect of maintenance training in a further group of 8 patients with coronary heart disease, 6 of whom were on beta-blocker therapy. By the end of the study, the heart rate achieved during exercise in the 17 patients was still significantly greater (P less than 0.0004) by 12.1 +/- 2.85 beats/min (mean +/- SEM) than that at the beginning of the trial; similar results were obtained in the 6 patients on beta-blocker therapy. Therefore a maintenance exercise training programme in patients with coronary heart disease can result in a sustained improvement in the form of a reduction in the severity of myocardial ischaemia, and this can occur in patients on beta-blocker therapy.

Adrenergic beta-Antagonists↗

Secretory IgA antibody in cervicovaginal secretions from women with genital infection due to herpes simplex virus.

Sequential samples of cervicovaginal secretions from women with untreated first and recurrent episodes of genital infection due to herpes simplex virus type 2 (HSV-2) were assayed for IgA antibodies to HSV-2 by using fluorescent antibodies to human secretory piece (sIgA) and human IgA. Among women with first-episode genital herpes, sIgA antibody to HSV-2 was detected in 20 of 31 women from whom HSV was isolated from the cervix, compared with four of 13 women from whom it was not (P less than .05). Among women with first-episode genital herpes, the mean titer of sIgA antibody to HSV-2 peaked between days 9 and 16 of disease, whereas among women with recurrent genital HSV, the peak occurred at days 3-8 of disease. HSV-2 was not isolated from the cervix from any of 130 samples taken when titers of sIgA antibody to HSV-2 were greater than or equal to 1:2, compared with 98 of 259 samples taken when titers were less than or equal to 1:2 (P less than or equal to .01).

Adult↗

Treatment of primary first-episode genital herpes simplex virus infections with acyclovir: results of topical, intravenous and oral therapy.

Three double-blind, placebo-controlled evaluations of acyclovir were performed in first-episode genital herpes infections. In one trial intravenous acyclovir or saline was administered in hospital over 5 days. In the other two trials, 10-day courses of oral, or 7-day courses of topical acyclovir and respective placebos were followed up in the outpatient department. Regular assessments included staging examinations, culture of lesions and blood and serum analyses. No patient discontinued medication because of an adverse reaction, although one quarter of topically treated patients complained of local irritation on application. The placebo-controlled evaluations indicate that, if given within the first 7 days after the onset of lesions, topical, intravenous and oral acyclovir are useful in shortening the course of first-episode primary genital herpes. The clinical and virological effects of intravenous and oral acyclovir were more marked than those of topical treatment in the reduction of viral shedding; the time to complete healing of lesions; and in the reduction of new lesion formation. Systemic preparations of acyclovir also decreased the symptoms of herpes simplex virus urethritis and intravenous acyclovir those of herpes simplex virus cervicitis. Neither systemic treatment, however, was effective in delaying or reducing the frequency of subsequent recurrences, which may be related to the development of early ganglionic infection. Despite this, acyclovir treatment is a significant advance in the management of primary genital herpes.

Acyclovir↗

Skin tumors induced by painting nitrosoalkylureas on mouse skin.

The carcinogenic action of nitrosamides has been investigated by applying a 0.04 M solution in acetone of 17 nitrosoalkylureas and one nitrosoalkylcarbamate to the shaved interscapular skin of female Swiss mice. Each of a group of 20 mice received 25 microliter of solution twice a week for 40 or 50 weeks, after which the animals were observed until death or 100 weeks. The appearance and progression of skin tumors within the painted area was charted for each animal. Nitroso-2-fluoroethylurea was toxic to the skin and was retested using a 0.01 M solution in acetone. No tumors was seen with nitrosoallylurea, nitroso-iso-butylurea, nitrosobenzylurea, and nitroso-2-phenylethylurea. The most potent compounds were nitrosomethylurea, nitrosoethylurea, and nitroso-2-fluoroethylurea. Nitroso-n-amylurea and nitroso-n-hexylurea were somewhat less potent, each inducing tumors in 11 of 20 mice. Nitrosocarbaryl gave rise to skin tumors in eight mice. The remaining compounds, nitroso-n-propylurea, nitroso-iso-propylurea, nitroso-n-butylurea, nictroso-sec-butylurea, nitroso-n-undecylurea, nitroso-n-tridecylurea, nitrosophenylurea, and nitrosocyclohexylurea were much less effective skin carcinogens, yielding tumors in from one to five mice. No good correlation was apparent between the relative stability of the compounds, their mutagenicity to Salmonella and their carcinogenicity to mouse skin.

Animals↗

Comparison of viral isolation, direct immunofluorescence, and indirect immunoperoxidase techniques for detection of genital herpes simplex virus infection.

Seventy-six consecutive patients presenting to a genital herpes simplex virus (HSV) clinic were enrolled in a study comparing viral isolation (VI), indirect immunoperoxidase (indirect IP), and direct immunofluorescence (direct FA) techniques for the detection of HSV antigen. Of the 76 patients, 61 (80%) demonstrated HSV by VI, compared with 66% by indirect IP and 55% by direct FA (P less than 0.05). Genital lesions from nine patients demonstrated HSV antigen by direct FA or indirect IP but were VI negative; eight of nine patients had subsequent episodes of genital HSV confirmed by VI. During the vesicular-pustular stage of the disease, VI was positive in 90%, indirect IP was positive in 76%, and direct FA was positive in 71% of the lesions, whereas with ulcerative lesions, VI was positive in 72%, indirect IP was positive in 55%, and direct FA was positive in 38%. These commercially available rapid viral diagnostic techniques are specific and useful, if adequate specimens are obtained from early genital lesions.

Antigens, Viral↗

Husband involvement in the behavioral treatment of overweight women: initial effects and long-term follow-up.

This study investigated whether husband participation would augment the effectieness of the Sturart & Davis (1972) weight-reduction program for 37 obese women. Following a five-week baseline period, participants were taught behavioral weight-control techniques in eight 90-minute sessions over a 16-week period. Random assignment was made to conditions that required husbands to participate in all treatment sessions, the first four sessions, or not at all. Results indicated that although women in all three conditions lost significant amounts of weight and developed more adaptive eating habits, husband involvement fostered reliably greater weight loss, which was maintained through a six-week post-treatment assessment. Participant husbands became more accurate observers of changes in their wives' eating habits and were viewed as being more helpful than were noninvolved husbands. A three-year follow-up indicated that the wives had maintained their initial weight losses and reported changes in eating habits, while the effects engendered by husband involvement had dissipated.

Adult↗

The abdominal muscle receptor organ in Astacus leptodactylus (Crustacea).

The structure of both the slow- and the fast-adapting abdominal muscle receptor organ of Astacus leptodactylus is described with particular reference to differences between the two systems. The receptors are composed of a thin muscle that extends from the front edge of one segment to the front edge of the following and a sensory cell connected with this muscle. In the zone where the sensory cells enter their respective muscle, muscle fibers are reduced (zone of relative muscle exclusion = ZRME) and partly replaced by connective tissue. The occurrence of dendritic processes of both the slow and the fast neurons is confined to this zone. The following differences between the two receptor types are established: (1) The fast receptor muscle reveals a smaller sarcomere length than the slow receptor muscle and a higher myosin/actin filament ratio. (2) Muscle fibers that pass the ZRME are always found at its periphery in the fast system, separated from dendritic processes by layers of connective tissue, while in the slow system muscle fibers frequently are intermingled with the sensory elements. (3) The ZRME of the slow receptor is 20-30% longer than that of the fast receptor. (4) The dendritic varicosities of the slow neuron, on an average, contain many more mitochondria than those of the fast neuron. (5) Dendritic processes (fine twigs as well as varicosities) are juxtaposed to the sarcolemma of the muscle fibers only in the slow system; in the fast system dendrites and muscle are spatially separated by connective tissue. It is assumed that these differences between the two receptor types are at least in part responsible for the different thresholds observed in physiological experiments.

Abdominal Muscles↗

The inhibition of isocitrate oxidation by palmitoyl-l-carnitine and palmitoyl-C0 A in rat liver mitochondria.

Palmitoyl-L carnitine decreases the oxidation of isocitrate in rat liver mitochondria in state 3 by 25-30%. Palmitoyl-L-carnitine acts as an additional substrate raising the rate of oxidative phosphorylation, NAD reduction and ATP/ADP ratio in mitochondria. Palmitoyl-CoA added to mitochondria oxidizing isocitrate in state 3 causes a strong inhibition of isocitrate oxidation and of oxidative phosphorylation and a considerable elevation of intramitochondrial NADH/NAD and ATP/ADP ratios. The effect of palmitoyl-CoA is dependent on its concentration and is competitive with ADP. Carnitine restores only oxidative phosphorylation, but the oxidation of isocitrate remains inhibited. Evidence is presented that the transport of isocitrate is not affected by palmitoyl-CoA is due to the inhibition of adenine nucleotide translocation. The kinetic studies of NAD-dependent isocitrate dehydrogenase in the soluble fraction of sonicated mitochondria revealed that the enzyme is very sensitive towards the inhibition by NADH and only very slightly affected by ATP (Ki for NADH and ATP are 0.017 and 3.6 mM respectively). On the basis of the kinetic data the relative contribution of NADH and ATP in the inhibition of isocitrate oxidation by fatty acids was calculated. It is concluded that the inhibition of isocitrate oxidation caused by palmitoyl-L-carnitine and palmitoyl-CoA is primarily due to the increased reduction of NAD, whereas the increase of ATP/ADP ratio is much less important.

Adenosine Diphosphate↗