PubMed Health⌕ Search

Biomedical subjects

K Allen

Publications and source records attributed to K Allen.

At least 19 recordsLinked to original sources
PubMed2001

Phylogenetic analysis of multiple heterosexual transmission events involving subtype b of HIV type 1.

Between 1996 and 1999 thirteen cases of HIV infection were detected in Doncaster, a small town in the north of England (population approximately 250,000). A complex network of shared sexual histories involving local nightclubs linked these cases, with the only known risk factor being heterosexual intercourse. A series of frozen blood samples was collected in 1998-1999 and amplified by PCR to generate full-length gp120 clones. Sequencing demonstrated that all the transmission events in this heterosexual group involved the B subtype of HIV-1. When relationships between the samples were assessed it became clear that these 13 cases represented at least three separate strains of HIV-1, indicating that HIV is well established in this community. Eleven of the 13 cases were related, forming two distinct groups. Further investigation revealed that one group contained five patients whose general health was good and who were not receiving HAART. In contrast, the second group of six patients, including the putative index case, were symptomatic, receiving HAART, and may have been infected with a CXCR-4-utilizing virus. Several of the cases that were linked by genetic criteria were not linked by contact tracing, implying that further undiagnosed cases may exist in this community. To our knowledge, this is the largest outbreak of HIV studied within the heterosexual community in the United Kingdom to date, suggesting that this route of infection is becoming more common within the United Kingdom.

Disease Outbreaks↗
PubMed2001

The changing attitudes of health professionals and consumers towards a coordinated care trial--SA HealthPlus.

The national coordinated care trials have been a vehicle for health reform in Australia, driven by escalating health care costs and projections of an ageing population. The first round of trials conducted between 1997 and 1999 set the trials a challenge to reduce financial and system barriers to enable health professionals in all sectors and consumers to develop service delivery models which would give better outcomes for patients within existing resources. As part of a change management strategy, the developers of the SA HealthPlus trial assessed the attitudes of health professionals and consumers involved in designing the projects which made up the larger trial, prior to trial development and twelve months later. This paper reports on the results of the survey and how initial enthusiasm gave way to appropriate anxiety as the complexities of creating a new system of care from reactive to prospective patient centred care planning, became a reality. The survey enabled trial developers to show evidence of acceptability for the new model of care and identify areas of concern and appropriate strategies for the project teams. This type of survey and the issues identified may be of benefit to the second round coordinated care trials and health regions aiming to initiate coordinated care programs.

Attitude to Health↗
PubMed2001

A vestibular phenotype for Waardenburg syndrome?

OBJECTIVE: To investigate vestibular abnormalities in subjects with Waardenburg syndrome. STUDY DESIGN: Retrospective record review. SETTING: Tertiary referral neurotology clinic. SUBJECTS: Twenty-two adult white subjects with clinical diagnosis of Waardenburg syndrome (10 type I and 12 type II). INTERVENTIONS: Evaluation for Waardenburg phenotype, history of vestibular and auditory symptoms, tests of vestibular and auditory function. MAIN OUTCOME MEASURES: Results of phenotyping, results of vestibular and auditory symptom review (history), results of vestibular and auditory function testing. RESULTS: Seventeen subjects were women, and 5 were men. Their ages ranged from 21 to 58 years (mean, 38 years). Sixteen of the 22 subjects sought treatment for vertigo, dizziness, or imbalance. For subjects with vestibular symptoms, the results of vestibuloocular tests (calorics, vestibular autorotation, and/or pseudorandom rotation) were abnormal in 77%, and the results of vestibulospinal function tests (computerized dynamic posturography, EquiTest) were abnormal in 57%, but there were no specific patterns of abnormality. Six had objective sensorineural hearing loss. Thirteen had an elevated summating/action potential (>0.40) on electrocochleography. All subjects except those with severe hearing loss (n = 3) had normal auditory brainstem response results. CONCLUSION: Patients with Waardenburg syndrome may experience primarily vestibular symptoms without hearing loss. Electrocochleography and vestibular function tests appear to be the most sensitive measures of otologic abnormalities in such patients.

Adult↗
PubMed2001

Polycyclic aromatic hydrocarbons, aliphatic hydrocarbons, trace elements, and monooxygenase activity in birds nesting on the North Platte River, Casper, Wyoming, USA.

Tree swallow (Tachycineta bicolor) and house wren (Troglodytes aedon) eggs and chicks were collected near a refinery site on the North Platte River, Casper. Wyoming, USA and at a reference site 10 km upstream. Total polycyclic aromatic hydrocarbon (PAH) concentrations in swallow and wren chicks were higher at the refinery site than at the reference site. Polycyclic aromatic hydrocarbon concentrations in sediment and chick dietary samples were consistent with these findings. The general lack of methylated PAHs in sediment, diet, and bird carcasses suggested that the PAHs were derived from combustion and not from petroleum. The predominance of odd-numbered aliphatic hydrocarbons and the low ratios (< or =0.25) of pristane:n-C17 and phytane:n-C18 in chick and diet samples also suggested that swallow and wren chicks were not being chronically exposed to petroleum. Mean ethoxyresorufin-O-dealkylase and benzyloxyresorufin-O-dealkylase activities in tree swallow livers averaged nine times higher at the refinery site than at the reference site and were probably induced by exposure to PAHs. Trace element concentrations in eggs and livers of swallows and wrens were similar or greater at the reference site than at the refinery site. Selenium, strontium, and boron concentrations were elevated in eggs and livers of swallows and wrens at both the refinery and reference sites.

Alkanes↗
PubMed2000

Missense mutation in PAK3, R67C, causes X-linked nonspecific mental retardation.

X-linked mental retardation is a very common condition that affects approximately 1 in 600 males. Despite recent progress, in most cases the molecular defects underlying this disorder remain unknown. Recently, a study using the candidate gene approach demonstrated the presence of mutations in PAK3 (p21-activating kinase) associated with nonspecific mental retardation. PAK3 is a member of the larger family of PAK genes. PAK proteins have been implicated as critical downstream effectors that link Rho-GTPases to the actin cytoskeleton and to MAP kinase cascades, including the c-Jun amino-terminal kinase (JNK) and p38. We screened 12 MRX pedigrees that map to a large region overlying Xq21-q24. Mutation screening of the whole coding region of the PAK3 gene was performed by using a combination of denaturing gradient gel electrophoresis and direct sequencing. We have identified a novel missense mutation in exon 2 of PAK3 gene (R67C) in MRX47. This confirms the involvement of PAK3 in MRX following the report of a nonsense mutation recently reported in MRX30. In the MRX47 family, all affected males show moderate to severe mental retardation. No seizures, statural growth deficiency, or minor facial or other abnormal physical features were observed. This mutation R67C is located in a conserved polybasic domain (AA 66-68) of the protein that is predicted to play a major role in the GTPases binding and stimulation of Pak activity.

Amino Acid Sequence↗
PubMed2000

Depression after stroke and lesion location: a systematic review.

BACKGROUND: There is conflicting evidence on the hypothesis that the risk of depression after stroke is influenced by the location of the brain lesion. We undertook a systematic review to examine the hypotheses that depression is more commonly associated with left-hemisphere strokes than with right-hemisphere strokes and with lesions of the left anterior brain than with other regions. METHODS: We did a computer-aided search of MEDLINE, BIDS ISI, and PsychLit databases supplemented by hand searches of key journals. We included all reports on the association of depression after stroke with the location of the brain lesion. Studies were systematically and independently examined by two investigators. Fixed-effects and random-effects meta-analyses were done. FINDINGS: 143 reports were identified by the search strategy. 48 were eligible for inclusion. Not all reports included original data. Only two reports of original data supported the hypotheses and seven clearly did not. The pooled (random-effects) relative risk of depression after a left-hemisphere stroke, compared with a right-hemisphere stroke, was 0.95 (95% CI 0.83-1.10). For depression after a left anterior lesion compared with all other brain areas the pooled (random-effects) relative risk was 1-17 (0.87-1.62). Restriction of the analyses to reports from high-quality studies or major depressive disorder did not substantially affect the findings. Nor were they affected by stratification of the time between stroke and the assessment of depression. Multiple publications from the same samples of patients were apparent. INTERPRETATION: This systematic review offered no support for the hypothesis that the risk of depression after stroke is affected by the location of the brain lesion.

Aphasia↗
PubMed2000

Android obesity at diagnosis and breast carcinoma survival: Evaluation of the effects of anthropometric variables at diagnosis, including body composition and body fat distribution and weight gain during life span,and survival from breast carcinoma.

BACKGROUND: Although a large body of research exists concerning pathologic prognostic indicators of the rate of incidence and survival from breast carcinoma, to the authors' knowledge very few studies have examined the effects of anthropometric variables such as height, obesity, weight gain in adulthood, timing of weight gain, and body composition to survival, although these variables are related to the incidence rate. METHODS: The survival status of 166 patients diagnosed with primary breast carcinoma and followed for at least 10 years was obtained from the Cancer Center's registry, and significant anthropometric and other known prognostic indicators regarding survival after diagnosis were determined by Cox proportional hazards analysis. RESULTS: Eighty-three of 166 breast carcinoma patients (50%) with up to 10 years of follow-up died of disease. Android body fat distribution, as indicated by a higher suprailiac:thigh ratio, was a statistically significant (P < 0.0001) prognostic indicator for survival after controlling for stage of disease, with a hazards ratio of 2.6 (95% confidence interval [95% CI], 1.63-4.17). Adult weight gain, as indicated specifically by weight at age 30 years, was a statistically significant (P < 0.05) prognostic indicator for survival with a hazards ratio of 1.15 (95% CI, 1.0-1.28). In addition, the authors observed the Quatelet Index, a negatively significant (P < 0.01) prognostic indicator for survival with a hazards ratio of 0.92 (95% CI, 0.87-0.98). Other markers of general obesity such as weight at diagnosis, percent body fat, and body surface area were not significant markers influencing survival. Similarly, height; triceps, biceps; subscapular, suprailiac, abdominal, and thigh skinfolds; waist and hip circumferences; family history; and reproductive and hormonal variables at the time of diagnosis showed no apparent significant relation to survival. CONCLUSIONS: The results of the current study provide some evidence that android body fat distribution at diagnosis and increased weight at age 30 years increases a woman's risk of dying of breast carcinoma.

Adult↗
PubMed2000

Ca(2+) measurements in skinned cardiac fibers: effects of Mg(2+) on Ca(2+) activation of force and fiber ATPase.

In contrast to previous studies, a new fluorescent method was used to accurately determine the Ca(2+) concentration in test solutions used to activate skinned rat cardiac cells. This method used the calcium green-2 fluorescent indicator, which is shown to change its fluorescence over the Ca(2+) range responsible for Ca(2+) activation of force and ATPase. The dissociation constant (K(d)) of calcium green-2 for Ca(2+) was determined for three different Mg(2+) concentrations in solutions similar to those used in the experiment. Increasing Mg(2+) concentration from 1.0 to 8.0 mM had no significant effect on the Ca(2+) sensitivity of either force or actomyosin ATPase activity, in contrast to previous reported studies on force. The ATPase activity was activated at lower Ca(2+) concentration than the force. The ratio (ATPase/force) is proportional to the dissociation rate of force-generating myosin cross bridges and decreased during Ca(2+) activation. These findings are consistent with the hypothesis that cardiac muscle contraction is activated by a single Ca(2+)-specific binding site on troponin C.

Actomyosin↗
PubMed1999

Passive smoking and the risk of coronary heart disease--a meta-analysis of epidemiologic studies.

BACKGROUND: The effect of passive smoking on the risk of coronary heart disease is controversial. We conducted a meta-analysis of the risk of coronary heart disease associated with passive smoking among nonsmokers. METHODS: We searched the Medline and Dissertation Abstracts Online data bases and reviewed citations in relevant articles to identify 18 epidemiologic (10 cohort and 8 case-control) studies that met prestated inclusion criteria. Information on the designs of the studies, the characteristics of the study subjects, exposure and outcome measures, control for potential confounding factors, and risk estimates was abstracted independently by three investigators using a standardized protocol. RESULTS: Overall, nonsmokers exposed to environmental smoke had a relative risk of coronary heart disease of 1.25 (95 percent confidence interval, 1.17 to 1.32) as compared with nonsmokers not exposed to smoke. Passive smoking was consistently associated with an increased relative risk of coronary heart disease in cohort studies (relative risk, 1.21; 95 percent confidence interval, 1.14 to 1.30), in case-control studies (relative risk, 1.51; 95 percent confidence interval, 1.26 to 1.81), in men (relative risk, 1.22; 95 percent confidence interval, 1.10 to 1.35), in women (relative risk, 1.24; 95 percent confidence interval, 1.15 to 1.34), and in those exposed to smoking at home (relative risk, 1.17; 95 percent confidence interval, 1.11 to 1.24) or in the workplace (relative risk, 1.11; 95 percent confidence interval, 1.00 to 1.23). A significant dose-response relation was identified, with respective relative risks of 1.23 and 1.31 for nonsmokers who were exposed to the smoke of 1 to 19 cigarettes per day and those who were exposed to the smoke of 20 or more cigarettes per day, as compared with nonsmokers not exposed to smoke (P=0.006 for linear trend). CONCLUSIONS: Passive smoking is associated with a small increase in the risk of coronary heart disease. Given the high prevalence of cigarette smoking, the public health consequences of passive smoking with regard to coronary heart disease may be important.

Coronary Disease↗
PubMed1999

Tidal breathing parameters in young children: comparison of measurement by respiratory inductance plethysmography to a facemask pneumotachograph system.

The ratio of expiratory time at tidal peak flow to total expiratory time (t(ptef)/t(e)) correlates with conventional measures of airway obstruction. It is usually assessed using a facemask and pneumotachograph system which may be poorly tolerated in young children and hence limits the usefulness of this technique. We therefore determined in young asthmatic children the accuracy of t(ptef)/t(e), using an uncalibrated respiratory inductance plethysmograph (RIP), and compared the results with those from a facemask-pneumotachograph system. We also assessed whether age influenced the agreement between measurements using the two devices. Forty-seven children aged between 1 month and 12 years were recruited: 39 were inpatients recovering from an acute wheezy episode, and 8 were recruited from the asthma clinic. All were receiving bronchodilators. Tidal breathing parameters t(ptef)/t(e), the duty cycle (t(i)/t(tot)), and respiratory rate were initially measured using the Respitrace alone and then simultaneously with both the Respitrace and the facemask-pneumotachograph system. Eight children did not tolerate the facemask, and in two others it was impossible to analyze the Respitrace trace due to artefacts. In the remaining 37 children, the reliability coefficients and coefficients of variation of the two techniques were similar. Similar values of t(i)/t(tot) and respiratory rate were obtained using the two devices. The mean t(ptef)/t(e) obtained using the Respitrace was lower than with the facemask-pneumotachograph system (P < 0.01), although this was age group-dependent (P < 0.05), as the difference was less apparent in the 1 to 2-year-old children than in other age groups. Application of the facemask-pneumotachograph system did not significantly influence the results obtained using the Respitrace. We conclude that uncalibrated respiratory inductance plethysmography can measure tidal breathing parameters as reliably as a facemask-pneumotachograph system in young asthmatic children, and is better tolerated than the pneumotachograph system. The results obtained using the two devices are not interchangeable.

Age Factors↗
PubMed1999

Simian immunodeficiency virus and human immunodeficiency virus type 1 nef proteins show distinct patterns and mechanisms of Src kinase activation.

The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases. We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity. Unexpectedly, however, the interaction of SIV Nef with human Lck or Hck is not mediated via its consensus proline motif, which is known to mediate HIV-1 Nef binding to Src homology 3 (SH3) domains, and various experimental analyses failed to show significant interaction of SIV Nef with the SH3 domain of either kinase. Instead, SIV Nef can bind Lck and Hck SH2 domains, and its N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation. Our results provide evidence for multiple mechanisms by which Nef binds to and regulates Src kinases.

Amino Acid Sequence↗
PubMed1999

Evidence for a protein mutator in yeast: role of the Hsp70-related chaperone ssb in formation, stability, and toxicity of the [PSI] prion.

Propagation of the yeast protein-based non-Mendelian element [PSI], a prion-like form of the release factor Sup35, was shown to be regulated by the interplay between chaperone proteins Hsp104 and Hsp70. While overproduction of Hsp104 protein cures cells of [PSI], overproduction of the Ssa1 protein of the Hsp70 family protects [PSI] from the curing effect of Hsp104. Here we demonstrate that another protein of the Hsp70 family, Ssb, previously implicated in nascent polypeptide folding and protein turnover, exhibits effects on [PSI] which are opposite those of Ssa. Ssb overproduction increases, while Ssb depletion decreases, [PSI] curing by the overproduced Hsp104. Both spontaneous [PSI] formation and [PSI] induction by overproduction of the homologous or heterologous Sup35 protein are increased significantly in the strain lacking Ssb. This is the first example when inactivation of an unrelated cellular protein facilitates prion formation. Ssb is therefore playing a role in protein-based inheritance, which is analogous to the role played by the products of mutator genes in nucleic acid-based inheritance. Ssb depletion also decreases toxicity of the overproduced Sup35 and causes extreme sensitivity to the [PSI]-curing chemical agent guanidine hydrochloride. Our data demonstrate that various members of the yeast Hsp70 family have diverged from each other in regard to their roles in prion propagation and suggest that Ssb could serve as a proofreading component of the enzymatic system, which prevents formation of prion aggregates.

Adenosine Triphosphatases↗
PubMed1999

Should we genetically test everyone for haemochromatosis?

The increasing availability of DNA-based diagnostic tests has raised issues about whether these should be applied to the population at large in order to identify, treat or prevent a range of diseases. DNA tests raise concerns in the community for several reasons. There is the possibility of stigmatisation and discrimination between those who test positive and those who don't. High-risk individuals may be identified for whom no proven effective intervention is possible, or conversely may test "positive" for a disease that does not eventuate. Controversy concerning prenatal diagnosis and termination of affected pregnancies may arise. Haemochromatosis, however, is a disease that is not only treatable but also preventable if those at high risk are identified presymptomatically. This paper will identify and discuss key issues regarding DNA-based population screening for haemochromatosis, and argue that population-based genetic screening for haemochromatosis should be supported when a number of contentious issues are addressed. In the context of a health system with limited resources haemochromatosis is the paradigm of a disorder where there is an ethical and clinical imperative to encourage presymptomatic DNA testing for all in ethnically relevant communities.

Adolescent↗