Search PubMed⌕ Search

Biomedical subjects

R S Chapman

Publications and source records attributed to R S Chapman.

At least 19 recordsLinked to original sources
PubMed2007

High success rate of TB treatment among Bhutanese refugees in Nepal.

SETTING: Camps for refugees from Bhutan in south-east Nepal. OBJECTIVES: To evaluate the outcome of treatment of tuberculosis (TB) cases in the refugee camps. DESIGN: Cohort analysis of results of treatment of cases started on treatment from mid-July 1999 to mid-July 2004. RESULT: A total of 1214 patients with TB were notified in the programme. Among these, 631 (52%) were new smear-positive pulmonary tuberculosis (PTB) cases, 175 (14%) new smear-negative PTB cases, 290 (24%) new extra-pulmonary TB (EPTB) cases and 118 (10%) smear-positive retreatment cases. Treatment success was achieved in 1061 (94%). The proportion of new non-smear-positive cases who died on treatment was significantly higher than the corresponding figure for new smear-positive cases (RR 7.57, 95%CI 3.74-15.32 for new smear-negative and 4.22, 95%CI 2.08-8.55 for EPTB). CONCLUSION: High cure rates and low bacteriological failure rates can be achieved in refugee settings if there is close coordination and collaboration between the local health agencies and the National Tuberculosis Programme of the host country.

Antitubercular Agents↗
PubMed2006

Surveillance of sexually transmitted diseases in general practice: a description of trends in the Royal College of General Practitioners Weekly Returns Service between 1994 and 2001.

This paper describes the incidence of sexually transmitted infections (STIs) recorded in the Weekly Returns Service (WRS) between 1994 and 2001. There were approximately 76,500 new diagnoses of STIs (7500 males, 71,000 females) and associated syndromes. Candidiasis was the commonest condition reported in males and females followed by pelvic inflammatory disease. The ratio of males to females was 7.1 for non-specific urethritis, and 9.1 and 2.1 for Reiter's syndrome and pediculosis pubis, respectively. The incidence of anogenital warts and genital herpes changed little over time. New diagnoses of genital herpes were higher in females than in males (ratio 2.8:1), whereas the mean annual incidence of genital warts was similar in males and females. The WRS provides an insight into the burden of STI diagnoses, and diagnoses related to STIs that are managed in general practice, and as such has the potential to make a substantial contribution to STI surveillance in England.

Adolescent↗
PubMed2004

Gender difference in the incidence of shingles.

We investigated age- and gender-specific incidence of shingles reported in a large sentinel practice network monitoring a defined population over the years 1994-2001. In total, 5915 male and 8617 female incident cases were studied. For each age group, we calculated the relative risk of females to males presenting with shingles. Incidence rates of chickenpox and herpes simplex were examined similarly. Shingles incidence was greater in females in each age group (except for 15-24 years). Relative risks (female to male) were greatest in age groups 45-64 years (1.48) and 0-14 years (1.43). There were no gender differences in the incidence of chickenpox except in the 15-24 years age group (female excess): for herpes simplex there were female excesses in all age groups. Gender-specific age-standardized incidence rates of shingles were calculated for each year and showed a consistent female excess in each of the 8 years (average annual excess 28%).

Adolescent↗
PubMed2004

Predictors of parent-child language during novel task play: a comparison between typically developing children and individuals with Down syndrome.

Three questions were asked that explored the linguistic fine-tuning hypothesis and how parents might model language: (i) do parents significantly tune to their children's productive language or non-verbal cognition during play? (ii) is the level of the linguistic tuning different in the Down syndrome (DS) population compared to a typically developing (TD)-match group population? and (iii) do the two populations differ in requests for labels and the scaffolding responses to the requests? In an exploratory play condition, parents of children with DS used a mean length of utterance (MLU) significantly higher than the MLU used by the parents of younger TD children who were matched for MLU. Thus, the DS parents have a higher baseline MLU, but the non-significant correlations in the DS group do not support parental MLU tuning. There was evidence, however, for parental tuning to the children's lexicon using a number of different words when the DS children were at lower and average levels of receptive syntax and non-verbal cognition. In addition, DS and TD parents requested labels for novel toys with the same frequency, perhaps indicating that all groups of parents are still probing and building their children's lexicons. This is an important finding because it may help to explain why adolescents and young adults with DS have vocabulary comprehension skills greater than one would predict from measures of their production and non-verbal cognition.

Adolescent↗
PubMed2004

Surveillance of the bioterrorist threat: a primary care response.

Threats from bioterrorism are of national and international concern. We outline a system of disease surveillance covering a selection of diseases linked to potential bioterrorist threats, based on the weekly returns service of the Royal College of General Practitioners and covering a surveillance population of 650,000 in England and Wales. Practices record working diagnoses and the episode type (distinguishing new episodes of illness from ongoing consultations) on patients' computerised medical records. These are interrogated twice weekly by using automated routines. The registered population and persons consulting for each Read code (group of codes) are counted in sex and age specific groups and the data forwarded electronically to the Research Unit, where the results are consolidated by region (North, Central, South). Weekly incidence rates between October 2001 and September 2002 were compared with the weekly average over the past seven years for 13 selected conditions. Detailed data are presented for three conditions (asthma, infections of the skin, disorders of the peripheral nervous system). For asthma increased incidence was reported in weeks 31 and 32 of 2002, predominantly in the Central region. For the other two conditions no unusual peaks of incidence were observed in any region. Operational research based on disciplined recording of morbidity in general practice can deliver timely surveillance data on bioterrorist threats.

Asthma↗
PubMed2001

p53-dependent apoptosis induced by proteasome inhibition in mammary epithelial cells.

We have examined the effects of inhibition of the 26S proteasome in a murine mammary cell line, KIM-2 cells using the peptide aldehyde inhibitor MG132. These studies have demonstrated a clear requirement for proteasome function in cell viability. Induction of apoptosis was observed following MG132 treatment in KIM-2 cells and this death was shown to be dependent on the cell actively traversing the cell cycle. KIM-2 cells were generated using a temperature sensitive T-antigen (Tag) and studies at the permissive temperature (33 degrees C) have shown that a Tag binding protein was essential for this apoptotic response. Studies in two additional cell lines, HC11, which is a mammary epithelial cell line carrying mutant p53 alleles and p53 null ES cells suggest that p53 is actively required for the apoptosis induced as a consequence of proteasome inhibition. These results suggest a pivotal role for the 26S proteasome degradation pathway in progression through the cell cycle in proliferating cells.

Animals↗
PubMed2001

Language, cognition, and short-term memory in individuals with Down syndrome.

The developmentally emerging phenotype of language and cognition in individuals with Down syndrome is summarized on the basis of the project's prior work. Identified are a) the emerging divergence of expressive and receptive language, b) the emerging divergence of lexical and syntactic knowledge in each process, and c) the emerging divergence within cognitive skills of auditory short-term memory and visuospatial short-term memory from other visuospatial skills. Expressive syntax and auditory short-term memory are identified as areas of particular difficulty. Evidence for the continued acquisition of language skills in adolescence is presented. The role of the two components of working memory, auditory and visual, in language development is investigated in studies of narrative and longitudinal change in language skills. Predictors of individual differences during six years of language development are evaluated through hierarchical linear modelling. Chronological age, visuospatial short-term memory, and auditory-short term memory are identified as key predictors of performance at study entry, but not individual change over time, for expressive syntax. The same predictors account for variation in comprehension skill at study outset; and change over the six years can be predicted by chronological age and the change in visuospatial short-term memory skills.

Cognition Disorders↗
PubMed2000

A novel role for IRF-1 as a suppressor of apoptosis.

The tumour suppressor IRF-1 is a transcription factor involved in the induction of apoptosis in several in vitro systems. Post-lactational involution of the mammary gland is characterized by extensive apoptosis of the epithelial cells. We have previously shown that signal transducer and activator of transcription (Stat) 3 drives apoptosis and involution in the mouse mammary gland. Since one of the downstream targets of the Stat signalling pathway is IRF-1, we have used IRF-1 knockout mice to address the potential role of this transcription factor in involution. Surprisingly, in the absence of IRF-1 significantly higher numbers of apoptotic cells were found in involuting glands at 48 h compared to control glands. In addition, the alveolar structure in IRF-1 null mammary glands had collapsed whereas in control glands the alveoli remained intact and distended. However, by 72 h control and null glands were morphologically similar suggesting that IRF-1 suppresses apoptosis only during the early, reversible, stage of involution. This suggests a survival role for IRF-1 in mammary epithelia and demonstrates a novel role for IRF-1 in vivo--suppression of premature epithelial apoptosis during mammary gland involution.

Animals↗
PubMed2000

A novel cell culture model for studying differentiation and apoptosis in the mouse mammary gland.

BACKGROUND: This paper describes the derivation and characterization of a novel, conditionally immortal mammary epithelial cell line named KIM-2. These cells were derived from mid-pregnant mammary glands of a mouse harbouring one to two copies of a transgene comprised of the ovine beta-lactoglobulin milk protein gene promoter, driving expression of a temperature-sensitive variant of simian virus-40 (SV40) large T antigen (T-Ag). RESULTS: KIM-2 cells have a characteristic luminal epithelial cell morphology and a stable, nontransformed phenotype at the semipermissive temperature of 37 degrees C. In contrast, at the permissive temperature of 33 degrees C the cells have an elongated spindle-like morphology and become transformed after prolonged culture. Differentiation of KIM-2 cells at 37 degrees C, in response to lactogenic hormones, results in the formation of polarized dome-like structures with tight junctions. This is accompanied by expression of the milk protein genes that encode beta-casein and whey acidic protein (WAP), and activation of the prolactin signalling molecule, signal transducer and activator of transcription (STAT)5. Fully differentiated KIM-2 cultures at 37 degrees C become dependent on lactogenic hormones for survival and undergo extensive apoptosis upon hormone withdrawal, as indicated by nuclear morphology and flow cytometric analysis. KIM-2 cells can be genetically modified by stable transfection and clonal lines isolated that retain the characteristics of untransfected cells. CONCLUSION: KIM-2 cells are a valuable addition, therefore, to currently available lines of mammary epithelial cells. Their capacity for extensive differentiation in the absence of exogenously added basement membrane, and ability to undergo apoptosis in response to physiological signals will provide an invaluable model system for the study of signal transduction pathways and transcriptional regulatory mechanisms that control differentiation and involution in the mammary gland.

Animals↗
PubMed2000

Behavioral phenotype of individuals with Down syndrome.

Evidence is reviewed for a developmentally-emerging behavioral phenotype in individuals with Down syndrome that includes significant delay in nonverbal cognitive development accompanied by additional, specific deficits in speech, language production, and auditory short-term memory in infancy and childhood, but fewer adaptive behavior problems than individuals with other cognitive disabilities. Evidence of dementia emerges for up to half the individuals studied after age 50. Research issues affecting control group selection in establishing phenotypic characteristics are discussed, as well as the possible genetic mechanisms underlying variation in general cognitive delay, specific language impairment, and adult dementia. MRDD Research Reviews 2000;6:84-95. Wiley-Liss, Inc.

Adaptation, Psychological↗
PubMed2000

The role of Stat3 in apoptosis and mammary gland involution. Conditional deletion of Stat3.

STATs (signal transducer and activator of transcription) are a family of latent transcription factors which are activated in response to a variety of cytokines and growth factors. This family of signalling molecules have been implicated in growth, differentiation, survival and apoptosis. In this article, we will review work which highlights the role of individual STAT factors in mammary gland and demonstrate the value of genetically modified mice in defining the function of STAT3. Involution of the mouse mammary gland is characterised by extensive apoptosis of the epithelial cells and the activation of STAT3. STATs 3 and 5 have reciprocal patterns of activation throughout a mammary developmental cycle suggesting that STAT5 may be a survival factor and STAT3 a death factor for differentiated mammary epithelium. To clarify the role of STAT3 in mammary epithelial apoptosis, we have generated a conditional knockout using the lox/Cre recombination system. Mammary glands from crosses of transgenic mice expressing Cre recombinase under the control of the beta-lactoglobulin milk protein gene promoter with mice harbouring one floxed STAT3 allele and one null STAT3 allele, showed a decrease in epithelial apoptosis and a dramatic delay of the involution process upon forced weaning. This was accompanied by precocious activation of STAT1 and increases in p53 and p21 levels--these may act as a compensatory mechanism for initiating the eventual involution which occurs in STAT3 null mammary glands. This demonstrates for the first time the importance of STAT factors in signalling the initiation of physiological apoptosis in vivo and highlights the utility of the lox/Cre system for addressing the function of genes, which have an embryonic lethal phenotype, specifically in mammary gland.

Animals↗
PubMed2000

Predicting language production in children and adolescents with Down syndrome: the role of comprehension.

Predictors of language production skills in 12-minute narratives are investigated cross-sectionally in 48 children and adolescents with Down syndrome (trisomy 21), aged 5 to 20 years, in comparison to 48 control children aged 2 to 6 years matched statistically for nonverbal mental age and mother's years of education. Two models were evaluated by hierarchical regression analyses using predictors drawn from the domains of group membership, chronological age, cognition, socioeconomic status, and hearing screening status (Model I) and, additionally, comprehension performance (Model II). Results showed that Model II was more successful. In the DS group, it explained 68% of the variability in number of different words, 80% in MLU, and 32% in intelligibility. Corresponding percentages for the control group were 72%, 71%, and 26%. A mechanism linking comprehension of input to early stages of production practice through activation of the early speech motor area is proposed.

Adolescent↗
PubMed2000

The relationship between event representation and linguistic skill in narratives of children and adolescents with Down syndrome.

Children and adolescents with Down syndrome present with greater difficulty in expressive language than nonverbal cognitive domains. As narratives involve an understanding of the relationship(s) between events and their verbal expression, this divergence has implications for understanding narrative abilities in persons with Down syndrome. In this project, we investigated the relationship between event representation and linguistic expression in narratives of children and adolescents with Down syndrome (n = 31) and groups of typically developing children matched for mental age (n = 31), syntax comprehension (n = 28), or expressive language (n = 27). A short wordless film, the Pear Story (Chafe, 1980), was viewed individually by each participant and then each participant retold the story to an adult who (presumably) had not seen the film. Findings suggest a disparate relationship between linguistic expression and event representation in narratives of children and adolescents with Down syndrome. Participants with Down syndrome produced narratives that were significantly longer and more complex than the expressive-language-matched-group, with no differences observed in event structure when compared to the MA-matched group. Comparatively, use of linguistic devices and cohesion were poorer in the children and adolescents with Down syndrome than in the MA-matched children, with no differences observed in comparison to children matched for expressive language.

Adolescent↗
PubMed2000

Children's language learning: an interactionist perspective.

This review of children's language learning considers historical accounts of acquisition and individual variation, recent advances in methods for studying language learning, research on genetic and environmental input that have contributed to the interactionist perspective, and the relevance of cross-disciplinary work on language disorders and the biology of learning to future theories. It concludes that the study of children's language development is converging on an interactionist perspective of how children learn to talk, incorporating the contributions of both nature and nurture to emergent, functional language systems. Language learning is viewed as an integration of learning in multiple domains.

Child↗
PubMed1999

Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3.

Mammary gland involution is characterized by extensive apoptosis of the epithelial cells. At the onset of involution, Stat3 is specifically activated. To address the function of this signaling molecule in mammary epithelial apoptosis, we have generated a conditional knockout of Stat3 using the Cre-lox recombination system. Following weaning, a decrease in apoptosis and a dramatic delay of involution occurred in Stat3 null mammary tissue. Involution is normally associated with a significant increase in IGFBP-5 levels. This was observed in control glands, but not in the absence of Stat3. IGFBP-5 has been suggested to induce apoptosis by sequestering IGF-1 to casein micelles, thereby inhibiting its survival function. Our findings suggest that IGFBP-5 is a direct or indirect target for Stat3 and its upregulation is essential to normal involution. No marked differences were seen in the regulation of Stat5, Bcl-x(L), or Bax in the absence of Stat3. Precocious activation of Stat1 and increases in levels of p53 and p21 occurred and may act as compensatory mechanisms for the eventual initiation of involution observed in Stat3 null mammary glands. This is the first demonstration of the importance of a Stat factor in signaling the initiation of physiological apoptosis in vivo.

Animals↗
PubMed1998

Lack of correlation of free deoxypyridinoline excretion with Taq1 restriction length polymorphisms in the vitamin D receptor gene in males.

An association between allelic variants in the vitamin D receptor gene and bone mineral density has been previously described. A bimodal variation in the rate of bone resorption (as measured by urinary deoxypyridinoline excretion rate) has also been reported. We have recruited male volunteers, to minimise variation associated with ovarian function, to investigate a possible connection between these observations. Allelic variants in the vitamin D receptor gene were identified as Taq1 restriction fragment length polymorphisms. The ratio of variants TT:Tt:tt occurred with a frequency of 34%:47%:17%. Excretion rates of urinary free deoxypyridinoline, measured by immunoassay, were compared in age-matched males from each genetic group. There were no significant differences based on the paired Student's t-test. Excretion rates declined with age (P = 0.04) and the best fit model fits the same regression line to each group. Genetic variation in the vitamin D receptor is not linked with differences in bone resorption rates.

Adult↗
PubMed1998

Language skills of children and adolescents with Down syndrome: II. Production deficits.

Hypotheses that children and adolescents with Down syndrome show (a) a specific expressive language impairment, (b) a "critical period" for language acquisition, (c) a "simple sentence syntactic ceiling" in production, and (d) deficit in grammatical morphology were investigated cross-sectionally. Conversational and narrative language samples from 47 children and adolescents with Down syndrome (Trisomy 21), aged 5 to 20 years, were compared to those from 47 control children aged 2 to 6 years matched statistically for nonverbal mental age. Children with Down syndrome appear to have a specific language impairment, compared to control children, in number of different words and total words (in the first 50 utterances) and in mean length of utterance (MLU). Total utterance attempts per minute were more frequent in the Down syndrome group. Narrative samples contained more word tokens, more word types, and longer MLU than conversation samples, for both groups. Intelligibility of narratives was significantly poorer for the Down syndrome group than controls. Analyses of narrative language sample by age sub-group showed no evidence of a critical period for language development ending at adolescence, nor of a "syntactic ceiling" at MLUs corresponding to simple sentences for the Down syndrome group. Omissions of word tokens and types were more frequent in the older Down syndrome than the younger control sample, matched on MLU.

Adolescent↗