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Biomedical subjects

H Simmons

Publications and source records attributed to H Simmons.

35 records · Page 2Linked to original sources
PubMed1991

Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure.

Studies of the mode of action of the bisphosphonate alendronate showed that 1 d after the injection of 0.4 mg/kg [3H]alendronate to newborn rats, 72% of the osteoclastic surface, 2% of the bone forming, and 13% of all other surfaces were densely labeled. Silver grains were seen above the osteoclasts and no other cells. 6 d later the label was 600-1,000 microns away from the epiphyseal plate and buried inside the bone, indicating normal growth and matrix deposition on top of alendronate-containing bone. Osteoclasts from adult animals, infused with parathyroid hormone-related peptide (1-34) and treated with 0.4 mg/kg alendronate subcutaneously for 2 d, all lacked ruffled border but not clear zone. In vitro alendronate bound to bone particles with a Kd of approximately 1 mM and a capacity of 100 nmol/mg at pH 7. At pH 3.5 binding was reduced by 50%. Alendronate inhibited bone resorption by isolated chicken or rat osteoclasts when the amount on the bone surface was around 1.3 x 10(-3) fmol/microns 2, which would produce a concentration of 0.1-1 mM in the resorption space if 50% were released. At these concentrations membrane leakiness to calcium was observed. These findings suggest that alendronate binds to resorption surfaces, is locally released during acidification, the rise in concentration stops resorption and membrane ruffling, without destroying the osteoclasts.

Alendronate↗
PubMed1986

A newly identified hepatitis B type virus in tree squirrels.

Virus-associated particles have been isolated from the livers of three common gray tree squirrels (Sciurus carolinensis pennsylvanicus) that have histological evidence of hepatitis. Two of these livers were also positive by orcein staining, suggesting the presence of surface antigen in the cytoplasm of hepatocytes. Fractionation of these particles by CsCl density equilibrium gradient centrifugation and assay of the fractions for surface antigen, core antigen, and DNA polymerase activities demonstrate the presence of all three at an approximate density peak of 1.27. Electron microscopic examination of purified virus preparations showed spherical particles with a mean diameter of 25 nm. Initial characterization of the DNA polymerase product by gel electrophoresis showed a single DNase I sensitive band, migrating slightly faster than the woodchuck hepatitis virus DNA polymerase product. The presence of apparently cross-reacting antibodies was demonstrated by purified hepatitis B surface and/or core antigens binding to some squirrel sera in solid phase assays. Infected tree squirrels appear to lack detectable antigen in their sera. These results suggest that the tree squirrels studied are chronic carriers of a hepatitis B type virus. The host-virus interaction described herein may be useful in understanding the chronic carrier state associated with hepatitis B in man.

Animals↗
PubMedDate not supplied

Woodchuck hepatitis virus: experimental infection and natural occurrence.

Sera from 588 woodchucks were assayed for woodchuck hepatitis virus (WHV) markers using hepatitis B virus (HBV) reagents which have cross-reactivity with WHV markers. Twenty per cent of these woodchucks, trapped in Delaware, Maryland and Pennsylvania, had WHsAg; 50% of these had DNA polymerase. There are areas of high and low endemicity within these states. Female woodchucks may have a higher incidence of WHV markers than do males. Woodchuck hepatitis surface antigen (WHsAg) and anti-WHc often occur together but less commonly than HBsAg and anti-HBc do in human HBV infection. Experimental infection of woodchucks with WHV produced a prolonged infection (up to 40 weeks). WHsAg and DNA polymerase appeared to be more reliable indicators of infectivity than anti-WHc, woodchuck hepatitis e antigen (WHeAg) or anti-WHe. WHeAg was not detected throughout this period of infection, while anti-WHe appeared late in two of three experimentally infected animals. Four male and four female woodchucks which developed primary hepatocellular carcinoma in captivity were analyzed for WHV markers throughout their period of confinement. Seven were WHsAg and anti-WHc positive when captured. The animal that was free of WHV markers on capture converted to the WHsAg and anti-WHc positive state prior to the development of primary hepatocellular carcinoma. One primary hepatocellular carcinoma animal produced WHeAg and none anti-WHs or anti-WHe.

Animals↗
PubMedDate not supplied

Prevalence of pervasive developmental disorders in the British nationwide survey of child mental health.

The prevalence of pervasive developmental disorders (PDD) is not well established and needs monitoring. We investigated the prevalence of PDDs in the 1999 nationwide British survey of child and adolescent mental health. A randomized stratified sample of children (n = 12,529) aged 5-15 was generated from Child Benefit Records. Trained interviewers interviewed parents and youths aged 11 or older with a standardized diagnostic interview (Development and Well-Being Assessment) and questionnaire data (Strengths and Difficulties Questionnaire) were obtained from teachers and parents who also completed self-report measures of psychological distress. A team of experienced clinicians using all data sources achieved final diagnostic determination. A total of 10,438 (83%) interviews were conducted. There were two girls with Rett syndrome (weighted prevalence: 3.8/10,000 girls) and 27 children with other PDDs (weighted prevalence: 26.1/10,000). Compared to children with a psychiatric disorder other than PDD, social but not behavioural problems were more frequent in the PDD group. Parents of children with PDDs had higher rates of psychological distress than those from the two comparison groups. Consistent with other recent surveys, PDD rates are higher than those reported 30 years ago. The burden associated with PDDs is very high.

Adolescent↗
PubMedDate not supplied

Using the Strengths and Difficulties Questionnaire (SDQ) to screen for child psychiatric disorders in a community sample.

Child psychiatric disorders are common and treatable, but often go undetected and therefore remain untreated. To assess the Strengths and Difficulties Questionnaire (SDQ) as a potential means for improving the detection of child psychiatric disorders in the community, SDQ predictions and independent psychiatric diagnoses were compared in a community sample of 7984 5-15 year olds from the 1999 British Child Mental Health Survey. Multi-informant (parents, teachers, older children) SDQs identified individuals with a psychiatric diagnosis with a specificity of 94.6% (95% Cl, 94.1-95.1%) and a sensitivity of 63.3% (59.7-66.9%). The questionnaires identified over 70% of individuals with conduct, hyperactivity, depressive, and some anxiety disorders, but fewer than 50% of individuals with specific phobias, separation anxiety and eating disorders. Sensitivity was substantially poorer with single-informant rather than multi-informant SDQs. Community screening programmes based on multi-informant SDQs could potentially increase the detection of child psychiatric disorders, thereby improving access to effective treatments.

Adolescent↗
PubMedDate not supplied

Prevalence of obsessive-compulsive disorder in the British nationwide survey of child mental health.

Obsessive-compulsive disorder (OCD) is a disorder that appears to be under-diagnosed and under-treated, despite the evidence for effective treatments. There are variable estimates of OCD prevalence in the under-16s and published rates give little indication of age trends. The aim of this study was to establish the prevalence and associates of OCD in young people aged 5-15 years. The method was a nationwide (UK) epidemiological study of rates of psychiatric disorder in 5-15 year olds (1999 British Child Mental Health Survey): 10,438 children were assessed. Twenty-five children with OCD were identified (weighted overall prevalence 0.25%; 95% CI 0.14-0.35), with prevalence rising exponentially with increasing age. Compared with normal controls, children with OCD were more likely to be from lower socio-economic class and of lower intelligence. Only three of these children had been seen by specialist children's services. Although OCD is rare in young children, the rate increases towards the adult rates at puberty. Children with OCD have additional psychosocial disadvantage. The majority of the childhood cases identified in this survey appear to have been undetected and untreated.

Adolescent↗