Sexual medicine. Models of integrated sexual health services already exist.
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Family Planning Services↗
Biomedical subjects
S Randall
Publications and source records attributed to S Randall.
A system for isolation, transport and storage of herpes simplex viruses.
A major difficulty with diagnostic virus isolation concerns the relative thermolability of certain viruses, e.g. herpes simplex virus type 2, which may, therefore, lose infectivity during transport to the laboratory. This study describes a system of virus isolation and transport, which depends on direct inoculation at the bedside or clinic, to a monolayer or suspension of susceptible cells with subsequent incubation for 10 h at approximately 32 degrees C, whereupon the newly synthesised virus becomes very stable if the cells are subsequently maintained at room temperature. This system was found to increase the sensitivity of isolation of herpes simplex virus, particularly under conditions of asymptomatic virus excretion or if there was significant delay in transportation of clinical samples to the virus laboratory. It is envisaged that this system will allow clinical self-sampling by the patient with application to epidemiological surveys in both the developed and underdeveloped world.
Animals↗
Mammalian mitogen-activated protein kinase pathways are regulated through formation of specific kinase-activator complexes.
Mammalian cells contain at least three signaling systems which are structurally related to the mitogen-activated protein kinase (MAPK) pathway. Growth factors acting through Ras primarily stimulate the Raf/MEK/MAPK cascade of protein kinases. In contrast, many stress-related signals such as heat shock, inflammatory cytokines, and hyperosmolarity induce the MEKK/SEK(MKK4)/SAPK(JNK) and/or the MKK3 or MKK6/p38(hog) pathways. Physiological agonists of these pathway types are either qualitatively or quantitatively distinct, suggesting few common proximal signaling elements, although past studies performed in vitro, or in cells using transient over-expression, reveal interaction between the components of all three pathways. These studies suggest a high degree of cross-talk apparently not seen in vivo. We have examined the possible molecular basis of the differing agonist profiles of these three MAPK pathways. We report preferential association between MAP kinases and their activators in eukaryotic cells. Furthermore, using the yeast 2-hybrid system, we show that association between these components can occur independent of additional eukaryotic proteins. We show that SAPK(JNK) or p38(hog) activation is specifically impaired by co-expression of cognate dominant negative MAP kinase kinase mutants, demonstrating functional specificity at this level. Further divergence and insulation of the stress pathways occurs proximal to the MAPK kinases since activation of the MAPK kinase kinase MEKK results in SAPK(JNK) activation but does not cause p38(hog) phosphorylation. Therefore, in intact cells, the three MAPK pathways may be independently regulated and their components show specificity in their interaction with cognate cascade members. The degree of intermolecular specificity suggests that mammalian MAPK signaling pathways may remain distinct without the need for specific scaffolding proteins to sequester components of individual pathways.
Animals↗
Antiviral properties of extract of Opuntia streptacantha.
An extract of the cactus plant Opuntia streptacantha inhibited intracellular virus replication and inactivated extracellular virus. Inhibition of virus replication also occurred following pre-infection treatment--a favourable finding in terms of in-vivo limitation of virus disease. There was inhibition of both DNA and RNA virus replication, for example, herpes simplex virus, equine herpes virus, pseudorabies virus, influenza virus, respiratory syncytial virus and human immunodeficiency virus, with normal protein synthesis in uninfected cells at extract concentrations which were 15-fold in excess of 50% viral inhibitory concentrations (1 mg/ml). The active inhibitory component(s) of the extract appeared to be protein in nature and resided mainly in the wall of the plant rather than in the cuticle or inner sap. The extract was non-toxic on oral administration to mice, horses and human patients; the non-toxicity of intravenous administration of 70 mg to a mouse representing at least fifty tissue culture 50% viral inhibitory dosages encourages clinical trial of this extract in virus disease of human and veterinary species.
Animals↗
Immunological studies of herpes simplex virus infection in children with atopic eczema.
This study examines the role of immune defence mechanisms in herpes simplex virus (HSV) infections in atopic eczema and whether impairment of these mechanisms explains the susceptibility of some children with atopic eczema to cutaneous HSV infections. Ten children with eczema herpeticum and 13 with atopic eczema and recurrent HSV infection affecting multiple skin sites were studied, together with relevant control groups. In all children with atopic eczema, in vitro lymphoproliferation in response to stimulation with concanavalin A (Con A) was significantly decreased and natural killer (NK) cells (CD16 + 56) were reduced compared with non-atopic controls. IL-2 receptors, a marker for lymphocyte activation, were decreased during the acute phase of eczema herpeticum, and for 1 month thereafter. A positive stimulation index (> 3) to HSV antigen, and high HSV IgG antibody titres measured by ELISA, Western blotting and neutralization assay, were seen in children with eczema herpeticum by 6 weeks, and also in children with atopic eczema and recurrent HSV infections. No evidence of an HSV-specific immune defect (either cell-mediated or humoral) was found in atopic eczema. Impairment of cell-mediated immunity in atopic eczema was suggested by the reduced response to Con A. It is likely that reduced numbers of circulating NK cells and a decrease in IL-2 receptors during early eczema herpeticum contribute to the susceptibility of children with atopic eczema to cutaneous HSV infections.
Acute Disease↗
Pregnant teenagers and contraception. The needs of older women are just as great.
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Adolescent↗
A dose-ranging study of the use of cyclical dydrogesterone with continuous 17 beta oestradiol.
OBJECTIVE: To establish the lowest dose of cyclical dydrogesterone that protects against endometrial hyperplasia induced by continuous 2 mg 17 beta oestradiol, and to study the dose effect on vaginal bleeding and side effects. DESIGN: Double-blind, prospectively randomised dose-ranging study. SETTING: Menopause clinics in the UK and The Netherlands. SUBJECTS: Three hundred and seventy-one postmenopausal women with intact uteri, aged 40 to 60. INTERVENTIONS: Administration of six 28-day treatment cycles of continuous daily micronised 17 beta oestradiol with a randomly allocated dose of 5 to 20 mg of dydrogesterone added for the last 14 days of each. MAIN OUTCOME MEASURES: Histological assessment of adequate progestational endometrial response, bleeding patterns and adverse effects. RESULTS: The study was completed by 320 subjects (86%). Endometrial transformation occurred in over 94% of those taking 5 mg of dydrogesterone, and in over 97% of those on higher doses, without significant differences between the 10, 15 and 20 mg groups. Acceptable bleeding patterns were found at all doses, with the incidence of withdrawal bleeding rising with increasing dose. The day of onset of bleeding was predictable from cycle to cycle, and occurred later in the 20 mg group than in the others. The incidence of noncyclic bleeding was about 6% at all doses. Withdrawal occurred in 3.3% due to unacceptable bleeding and in 5.4% due to side effects. There was no relation with dose. CONCLUSIONS: A dydrogesterone-17 beta oestradiol combination hormone replacement therapy confers endometrial protection with an acceptable bleeding pattern and few side effects At least 10 mg of dydrogesterone for 14 days is required for acceptable endometrial protection.
Adult↗
The neurokinin1 receptor antagonist CP-99,994 reduces catalepsy produced by the dopamine D2 receptor antagonist raclopride: correlation with extracellular acetylcholine levels in striatum.
The ability of the substance P (NK1) receptor antagonist CP-99,994 to alter catalepsy induced by a dopamine D1 or D2 receptor antagonist and the ability of CP-99,994 to influence acetylcholine (ACh) release in the striatum were investigated in rats. Catalepsy produced by the D1 antagonist SCH 23390 (0.5 mg/kg s.c.) was not altered by CP-99,994 (0.5, 2.5, or 10 mg/kg s.c.). In contrast, catalepsy induced by the D2 antagonist raclopride (2.5 mg/kg i.p.) was attenuated by CP-99,994 (2.5 and 10 mg/kg). CP-99,994 (10 mg/kg) did not stimulate locomotion when given alone. The less active enantiomer of CP-99,994, CP-100,263 (10 mg/kg), did not alter raclopride-induced catalepsy. Both systemic administration and intrastriatal perfusion of CP-99,994 alone decreased striatal ACh release. Bilateral intrastriatal perfusion of CP-99,994 (40 and 100 microM) reduced catalepsy produced by raclopride and attenuated raclopride-induced increases in striatal ACh release. The reductions in the duration of catalepsy and decreases in striatal ACh release associated with CP-99,994 perfusion were positively correlated. These findings suggest that blockade of striatal NK1 receptors reduces catalepsy induced by a dopamine D2 antagonist, an effect mediated, at least in part, by reducing striatal ACh release. Striatal NK1 receptors, therefore, may be a new therapeutic target for developing drugs that alleviate motor side effects associated with antipsychotic treatment.
Acetylcholine↗
Characterization and immunogenicity of a candidate subunit vaccine against varicella-zoster virus.
This study describes the properties of an inactivated subunit antigen preparation from varicella-zoster virus (VZV)-infected MRC-5 cells by treatment with detergent and formaldehyde, ultracentrifugation over sucrose and acetone precipitation. The method preserved the antigenicity of VZV proteins and several VZV-specific glycoproteins, while virus DNA was less than 20 pg/250 micrograms protein--a putative vaccine dose. The vaccine was immunogenic in rabbits and stimulated antibodies to the major capsid protein as well as to glycoproteins; an immunoprecipitin was shared with a known immune human serum. The preparation contained no infectious VZV with no evidence of side effects in a rabbit or in five human vaccinees during a follow-up period of 6-10 years.
Aged↗
Lithium gamma-linolenate-induced cytotoxicity against cells chronically infected with HIV-1.
Lithium gamma-linolenate (Li-GLA), was evaluated for its activity in selectively killing H9 cells chronically infected with HIV-1RF. After 4 days incubation with Li-GLA approximately 90% of the H9RF cells were non-viable compared to 20% of uninfected H9 cells. The efficacy of the Li-GLA, in preferentially killing HIV infected cells also correlates with lipid peroxidation, as measured by the intracellular thiobarbituric acid-reactive material content. The addition of an antioxidant (vitamin E) to the culture medium reduced the toxicity of Li-GLA. These data indicate that this selective killing effect of cells chronically infected with HIV may be due to the enhanced extent of lipid peroxidation of the added Li-GLA.
Antiviral Agents↗
Interactions of avian myeloblastosis virus nucleocapsid protein with nucleic acids.
The retroviral nucleocapsid protein (NC) associates, histone-like, with genomic RNA within the viral capsid. NC, an essential component of replication competent retroviruses, is also associated with events leading both to virus assembly and to reverse transcription. The nucleic acid binding properties of NC are key to understanding these properties, yet only a minimal biochemical description of NC-nucleic acid interactions is available. We have used the anisotropy of the intrinsic fluorescence of NC from avian myeloblastosis virus to quantify its binding to a variety of nucleic acids. Using salt back-titrations, the intrinsic equilibrium association constant per nucleic acid site, K(obs), was determined for NC binding to single- and double-stranded RNAs and DNAs. In 0.125 M NaCl, 40 mM HEPES at pH 7.0 and 27 degrees C, the log K(obs) ranged from 3.3 to 4.0 (average 3.7) for these nucleic acids. From the salt dependence of K(obs), it was estimated that, on balance, 1 ion was displaced upon formation of each complex; it is likely that cation displacement from nucleic acid is offset by anion binding by protein during complex formation. The logarithm of the mean intrinsic affinity in the absence of polyelectrolyte effects, log KT, was 3.1, corresponding to a delta G of -4.2 kcal/mol. K(obs), KT, and the number of displaced ions were independent of pH between pH 5.6 and 8.9, indicating that NC residues that titrate in this pH range are not contributing to binding. K(obs) and KT increase with temperature, in the range 15 to 47 degrees C. From van't Hoff analysis, entropy was found to be the driving force for formation of the NC-poly(rA) complex, even in the absence of the polyelectrolyte effect. The general nature of NC interactions with nucleic acids is shown by the similarity of the K(obs) values for RNAs and DNAs in both single-stranded and double-stranded structures. This ability of NC to interact with all types of nucleic acids may provide it with the necessary versatility to function like a histone in facilitating the packaging of viral RNA and yet function early in infection, where it has been ascribed a role in facilitating reverse transcription.
Avian Myeloblastosis Virus↗
Excess dietary lysine increases skeletal muscle and plasma trimethyllysine in rats.
Trimethyllysine, a carnitine precursor, is a cation. This study was designed to determine whether dietary potassium and lysine concentration or oral lysine supplementation affects tissue carnitine and trimethyllysine concentration in rats. In Experiment 1, rats were fed a control diet, a low or high potassium diet, or a high lysine diet. In Experiment 2, rats were given by gavage a solution containing either L-proline (control) or L-lysine. In Experiment 1, rats fed the high lysine diet had significantly lower plasma total carnitine concentration than controls. Rats fed the high lysine diets had significantly higher concentrations of free trimethyllysine in skeletal muscle and plasma relative to control rats and rats fed the high potassium diet. Rats fed the low potassium diet had a similar increase in skeletal muscle free trimethyllysine. In Experiment 2, rats given lysine had significantly lower plasma total carnitine concentration, and significantly greater skeletal muscle and plasma trimethyllysine concentration relative to controls. We conclude that dietary potassium and lysine, and oral lysine, have a significant effect upon the distribution of carnitine and trimethyllysine in rats. The distributional changes caused by lysine, however, seem to be due to effects other than exchange of lysine for carnitine or trimethyllysine in tissues.
Animals↗
The effects of lithium and potassium on macromolecular synthesis in herpes simplex virus-infected cells.
All herpes simplex virus (HSV) infected cell-specific polypeptides (ICSPs) were synthesized in the presence of lithium at a concentration (60 mM) inhibitory to the production of infectious virus. Yields of certain ICSPs were increased and others, in particular glycoprotein C, decreased. HSV DNA synthesis was completely inhibited; synthesis and in vitro activities of HSV DNA polymerase and thymidine kinase were decreased but to a degree insufficient to account for the complete inhibition of HSV DNA synthesis. HSV DNA synthesis was inhibited to an equivalent degree by either incubation with 60 mM-lithium or by potassium starvation; both procedures decreased intracellular potassium by an equivalent amount as adjudged by X-ray microanalysis. We conclude that lithium inhibits HSV DNA synthesis by displacement of potassium from a potassium-dependent biochemical reaction or by other physiological changes brought about by the loss of cellular potassium. The possibility that lithium also directly inhibits a virus replicative event cannot be excluded.
Animals↗
Issues in the demography of Mongolian nomadic pastoralism.
"Taking a historical perspective this paper examines the ecological and political influences on Mongolian demography. Changes in political policy, domestic economy, health services, venereal diseases and shortages of men are considered in examining the unusual pattern of very low fertility, followed by a rise in the 1950s and 1960s and a gradual fertility decline, even in the absence of modern contraception. It is concluded that the lack of simultaneity between major political and demographic changes suggest that there are no direct responses to policy, despite the strong pronatalist stance, but that health services, particularly in the realms of venereal disease treatment, have had a major influence on Mongolian demographic patterns. The indirect consequences of government policy--education, health services in rural areas, rapid urbanisation--appear to have a stronger influence than the pronatalism, and ironically have led to rapid fertility decline."
Asia↗
Molecular genetic analysis of bacteriophage P22 gene 3 product, a protein involved in the initiation of headful DNA packaging.
Bacteriophage P22 DNA packaging events occur in processive series on concatemeric phage DNA molecules. At the point where such series initiate, the DNA is recognized at a site called pac, and most molecular left ends are generated within six short regions called end sites, which are present in a 120 base-pair region surrounding the pac site. The bacteriophage P22 genes 2 and 3 proteins are required for successful generation of these ends and DNA packaging during progeny virion assembly. Mutants lacking the 162-amino-acid gene 3 protein replicate DNA and assemble functional procapsids. In this report we describe the nucleotide changes and DNA packaging phenotypes of a number of missense mutations of gene 3, which give the phage a higher than normal frequency of generalized transduction. In cells infected by these mutants, more packaging events initiate on the host chromosome than in wild-type infections, so the mutations are thought to affect the specificity of packaging initiation. In addition to having this phenotype, these mutations affect the process of phage DNA packaging in detectable ways. They may: (1) alter the target site specificity for packaging; (2) make target site recognition more promiscuous; (3) affect end site utilization; (4) alter the pac site; and (5) cause apparent random DNA packaging series initiation on phage DNA.
Bacteriophage P22↗
Bacteriophage P22 portal protein is part of the gauge that regulates packing density of intravirion DNA.
The complex double-stranded DNA bacteriophages assemble DNA-free protein shells (procapsids) that subsequently package DNA. In the case of several double-stranded DNA bacteriophages, including P22, packaging is associated with cutting of DNA from the concatemeric molecule that results from replication. The mature intravirion P22 DNA has both non-unique (circularly permuted) ends and a length that is determined by the procapsid. In all known cases, procapsids consist of an outer coat protein, an interior scaffolding protein that assists in the assembly of the coat protein shell, and a ring of 12 identical portal protein subunits through which the DNA is presumed to enter the procapsid. To investigate the role of the portal protein in cutting permuted DNA from concatemers, we have characterized P22 portal protein mutants. The effects of several single amino acid changes in the P22 portal protein on the length of the DNA packaged, the density to which DNA is condensed within the virion, and the outer radius of the capsid have been determined. The results obtained with one mutant (NT5/1a) indicate no change (+/- 0.5%) in the radius of the capsid, but mature DNA that is 4.7% longer and a packing density that is commensurately higher than those of wild-type P22. Thus, the portal protein is part of the gauge that regulates the length and packaging density of DNA in bacteriophage P22. We argue that these findings make models for DNA packaging less likely in which the packing density is a property solely of the coat protein shell or of the DNA itself.
Base Sequence↗
The solar wind and hallucinations--a possible relation due to magnetic disturbances.
Data from the 19th century on hallucinations and magnetic disturbances were found to exhibit a direct and statistically significant correlation. The aa magnetic index over the period 1868-89 and concurrent visual hallucinatory activity were found to co-vary (Spearman coefficient = .64; P less than .05). Magnetic influences on the pineal hormone, melatonin, are suggested as a possible source of variation.
Hallucinations↗
Initiation of SV40 DNA replication: mechanism and control.
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Cell Cycle↗