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Biomedical subjects

M Baker

Publications and source records attributed to M Baker.

At least 55 records · Page 3Linked to original sources
PubMed2000

No association between TAU haplotype and Alzheimer's disease in population or clinic based series or in familial disease.

We and others have previously identified two distinct haplotypes of the TAU gene in Caucasian populations. In this study, we have assessed whether these haplotypes show an association with Alzheimer's disease in a variety of populations. They do not. These data are consistent with the view that the involvement of TAU in Alzheimer's disease is a downstream event.

Age of Onset↗
PubMed2000

Cumulative incidence of hepatitis C seroconversion in a cohort of seronegative injecting drug users.

AIM: To measure the cumulative incidence of hepatitis C virus seroconversion over a two year period in a group of seronegative injecting drug users. METHODS: The study involved follow-up, in 1996, of a cohort (n=85) of injecting drug users identified as hepatitis C virus seronegative in 1994. Participants were interviewed about risk factors for hepatitis C. A blood sample was also taken for anti-hepatitis C virus antibody and hepatitis C virus RNA testing. RESULTS: Forty-four participants were interviewed and 39 gave blood for testing. Most (80%) were aged 29 years or under and two thirds (n=26) were male. Around half reported borrowing (49%) or lending (57%) needles and syringes since 1994 and both of these behaviours were associated with seroconversion. The majority (88%) also reported sharing other injecting equipment. Nine were anti-hepatitis C virus positive giving a seroconversion rate over two years of 23% (13 per 100 person years). Four out of the nine seropositive specimens tested were also hepatitis C virus RNA positive. CONCLUSIONS: This study demonstrates a high rate of recent hepatitis C virus seroconversion amongst a group of New Zealand injecting drug users. Transmission of hepatitis C virus appears to be unabated by current control measures. These findings confirm the need to develop more effective policy and practices to prevent further spread, not just of hepatitis C, but of other blood-borne viruses in injecting drug user populations.

Adolescent↗
PubMed2000

Prospective memory and aging: forgetting intentions over short delays.

Retrieved intentions often cannot be performed immediately and must be maintained until there is an opportunity to perform them. In 3 experiments, on seeing a target event, younger and older participants were to withhold an action until they encountered the appropriate phase of the experiment. When initial retrieval was made facile by the use of a salient retrieval cue, the age-related decrements were often dramatic, even over unfilled delay intervals as brief as 10 s (Experiments 1 and 2). When initial retrieval was difficult, older adults showed no forgetting over the retention interval (Experiment 3). Several theoretical perspectives were offered as explanations for the age differences observed with salient retrieval cues, including those that focus on age differences in metamemory, the degree to which plans are reformulated, and the ability to nonstrategically maintain current concerns in working memory.

Adolescent↗
PubMed2000

Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein.

Neurofibrillary tangles (NFT) composed of the microtubule-associated protein tau are prominent in Alzheimer disease (AD), Pick disease, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Mutations in the gene (Mtapt) encoding tau protein cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), thereby proving that tau dysfunction can directly result in neurodegeneration. Expression of human tau containing the most common FTDP-17 mutation (P301L) results in motor and behavioural deficits in transgenic mice, with age- and gene-dose-dependent development of NFT. This phenotype occurred as early as 6.5 months in hemizygous and 4.5 months in homozygous animals. NFT and Pick-body-like neuronal lesions occurred in the amygdala, septal nuclei, pre-optic nuclei, hypothalamus, midbrain, pons, medulla, deep cerebellar nuclei and spinal cord, with tau-immunoreactive pre-tangles in the cortex, hippocampus and basal ganglia. Areas with the most NFT had reactive gliosis. Spinal cord had axonal spheroids, anterior horn cell loss and axonal degeneration in anterior spinal roots. We also saw peripheral neuropathy and skeletal muscle with neurogenic atrophy. Brain and spinal cord contained insoluble tau that co-migrated with insoluble tau from AD and FTDP-17 brains. The phenotype of mice expressing P301L mutant tau mimics features of human tauopathies and provides a model for investigating the pathogenesis of diseases with NFT.

Amino Acid Substitution↗
PubMed2000

Evidence for a unique expression of CD4 on murine vaginal CD4+ cells.

Mucosal cell-mediated immunity (CMI) by CD4+ T cells is postulated to be important for host defence against several vaginal pathogens. In addition to the recognized phenotypic distinctions of resident vaginal T lymphocytes, we recently provided evidence by fluorescence-activated cell sorter (FACS) that murine vaginal CD4+ T lymphocytes, are differentially recognized by two epitope-distinct anti-CD4 antibodies, suggesting that the CD4 protein on vaginal CD4+ cells is atypically expressed. In the present study, we confirm this by FACS and immunohistochemistry under non-denaturing conditions using two additional anti-CD4 antibodies. However, positive immunohistochemical staining of vaginal CD4+ cells under denaturing conditions revealed that the CD4 epitope in question is indeed present within the CD4 protein. Using reverse transcription polymerase chain reaction, amplification of CD3, T-cell receptor-beta (TCR-beta), and TCR-delta mRNA from lymph node and vaginal tissue, and CD4 mRNA from lymph node tissue was demonstrable. In contrast, amplification of CD4 mRNA from vaginal tissue, vaginal enriched lymphoid cells, or a purified (FACS-sorted) population of vaginal-specific CD4+ cells using two distinct primer sets was not demonstrable. Altogether, our results provide evidence that the CD4 protein on vaginal CD4+ T cells is conformationally distinct compared with its systemic counterpart, either as a result of a unique CD4 mRNA sequence or from a stable interaction of soluble CD4 with the surface of vaginal T cells.

Animals↗
PubMed2000

The use of a thrombus-specific ultrasound contrast agent to detect thrombus in arteriovenous fistulae.

RATIONALE AND OBJECTIVES: To evaluate the use of a new thrombus-specific ultrasound contrast agent, MRX-408, in the ultrasonic detection of thrombus in arteriovenous (AV) fistulae. METHODS: Six purpose-bred mongrels with two AV fistulae each were imaged with gray-scale ultrasound 7 weeks after graft implantation before and after the intravenous bolus injection of MRX-408 (a GPIIb receptor-targeted ultrasound contrast agent). Pre- and postcontrast videotaped segments were randomized and reviewed by four radiologists blinded to the presence of thrombus in the grafts. RESULTS: After the use of MRX-408, there was improved visualization of thrombus within the grafts (P < 0.0001). This was due to the enhancement of the thrombus (P < 0.0001). The improved visualization and contrast enhancement were more marked in the grafts that contained thrombus nonhyperechoic to surrounding soft tissues. CONCLUSIONS: MRX-408 demonstrated better visualization of thrombus within AV fistulae. This was shown in both patent and occluded grafts. These results are encouraging and suggest that this contrast agent merits further development.

Animals↗
PubMed2000

Household crowding a major risk factor for epidemic meningococcal disease in Auckland children.

BACKGROUND: New Zealand is in its ninth year of a serogroup B meningococcal disease epidemic with annual rates of up to 16.9 cases per 100,000. The highest incidence is in Maori and Pacific Island children in the Auckland region. We conducted a case-control study to identify potentially modifiable risk factors for this disease. METHODS: A case-control study of 202 cases of confirmed and probable meningococcal disease in Auckland children younger than 8 years of age recruited from May, 1997, to March, 1999, was undertaken. Controls (313) were recruited door-to-door by a cluster sampling method based on starting points randomly distributed in the Auckland region. They were frequency matched with the expected distribution of age and ethnicity in the meningococcal disease cases. RESULTS: With the use of a multivariate model and controlling for age, ethnicity, season and socioeconomic factors, risk of disease was strongly associated with overcrowding as measured by the number of adolescent and adult (10 years or older) household members per room [odds ratio (OR), 10.7; 95% confidence interval (CI), 3.9 to 29.5]. This would result in a doubling of risk with the addition of 2 adolescents or adults to a 6-room house. Risk of disease was also associated with analgesic use by the child, which was thought to be a marker of recent illness (OR 2.4, CI 1.5 to 4.0); number of days at substantial social gatherings (10 or more people for > 4 h; OR 1.8, CI 1.2 to 2.6); number of smokers in the household (OR 1.4, CI 1.0 to 1.8); sharing an item of food, drink or a pacifier (OR 1.6, CI 1.0 to 2.7); and preceding symptoms of a respiratory infection (cough, "cold or flu," runny nose, sneezing) in a household member (OR 1.5, CI 1.0 to 2.5). CONCLUSION: Some of these identified risk factors for meningococcal disease are modifiable. Measures to reduce overcrowding could have a marked effect on reducing the incidence of this disease in Auckland children.

Adolescent↗
PubMed2000

The association between abuse in childhood and STD/HIV risk behaviours in female genitourinary (GU) clinic attendees.

OBJECTIVES: To compare and contrast women with a history of child abuse with those who have no history of child abuse on STI/HIV risk behaviours and safer sex beliefs in an inner city UK sample. DESIGN: Cross sectional sample survey. METHODS: Routine female clinic attendees were invited to complete an anonymous self report questionnaire which included background information, sexual and drug risk behaviour, self reported sexually transmitted infections (STIs), psychological distress (Hospital and Anxiety Depression Scale; HADS), Sexual Risk Cognitions Questionnaire (SRCQ), and history of child sexual, physical, and emotional abuse. RESULTS: 137 (45%) of 303 women reported a history of child abuse; all three forms of child abuse--sexual (26%), physical (20%), and emotional (27%) abuse--overlapped. The majority of women reported one sexual partner in the past month, and the majority did not use condoms. Women reporting a history of child abuse were more likely to have had previous STIs (p = 0.007) and to have had more than one STI (p = 0.04) compared with women who had not experienced child abuse. Injecting drug use and commercial sex work were of low prevalence across the whole sample and no group differences were found. Women reporting a history of child abuse had higher HADS anxiety (p = 0.03) compared with women with no history of child abuse. Confidence in using condoms with a sexual partner was not related to child abuse. Women with a history of child abuse reported significantly higher frequency of thoughts reflecting anticipated negative reactions from partners to suggesting condom use (p = 0.02) and judging a partner's risk by their appearance (p = 0.05) compared with women with no history of child abuse. CONCLUSIONS: Comparable rates of child sexual abuse with US studies were found in this UK inner city population of women attending sexual health services. Women who had experienced child abuse were more likely to report ever having had an STI and having had more than one STI. Complex psychological and social factors contribute to difficulties for women in negotiating safer sex including emotional distress, abuse histories, and anticipating a negative reaction from partners. Multifaceted prevention models are needed.

Adolescent↗
PubMed2000

MHC polymorphism in rodent plantaris muscle: effects of mechanical overload and hypothyroidism.

In a previous study, it was shown that a combined treatment of hyperthyroidism and hindlimb suspension effectively converted the slow-twitch soleus muscle to a fast-twitch muscle. The objective of this study was to test the hypothesis that hypothyroidism [absence of triiodothyronine (-T(3))] and mechanical overload (OV) would convert the plantaris (Plan) muscle from a fast- to a slow-twitch muscle. Single-fiber analyses demonstrated that the normal rodent Plan muscle was composed of approximately 13 different fiber types as defined by myosin heavy chain (MHC) isoform content. The largest proportion of fibers ( approximately 35%) coexpressed the fast type IIX and IIB MHC isoforms (i.e., type IIX/IIB fibers). In this context, the combined intervention of -T(3) and OV produced a significant reduction in the relative proportion of the fast type IIB MHC isoform and a concomitant increase in the slow type I MHC isoform. These transitions were manifested by a large decrease in the proportion of type IIX/IIB fibers and a large increase in fibers coexpressing all four MHC protein isoforms. The mechanical consequences of these transitions, however, were modest, producing a 15% decrease in maximal shortening velocity. The findings of this study demonstrate that -T(3) + OV does produce a partial shift toward a slower phenotype; however, the high degree of polymorphism found in the Plan muscle represents a unique design that appears to minimize the functional consequences of these significant MHC transitions.

Animals↗
PubMed2000

The work commitments of British general practitioners: a national survey.

Many qualified general practitioners (GPs) are choosing not to become principals. With the current problems in recruitment and retention of GPs, workforce planning for the future of general practice is contingent upon the work commitments of both GP principals and non-principals. A questionnaire survey of 5966 vocationally trained doctors in the UK suggests that shortfalls in the GP workforce will not be alleviated by relying on the non-principal pool increasing their time commitment to general practice work.

Career Choice↗
PubMed2000

Variant Alzheimer's disease with spastic paraparesis and cotton wool plaques is caused by PS-1 mutations that lead to exceptionally high amyloid-beta concentrations.

We describe 3 new families affected by Alzheimer's disease with spastic paraparesis. In affected individuals, including the earliest known patient with this clinical syndrome, neuropathological examination revealed large "cotton wool" plaques similar to those we have previously described in a Finnish family. In the families in which DNA was available, presenilin-1 mutations were observed. Transfection of cells with these mutant genes caused exceptionally large increases in secreted Abeta42 levels. Furthermore, brain tissue from individuals with this syndrome had very high amyloid-beta concentrations. These findings define the molecular pathogenesis of an important subgroup of Alzheimer's disease and have implications for the pathogenesis of the disease in general.

Alzheimer Disease↗
PubMed2000

Pick's disease is associated with mutations in the tau gene.

Recently, mutations within the tau gene have been associated with some familial forms of frontotemporal dementia. To investigate whether tau gene mutations are also associated with Pick's disease, we analyzed the tau gene in 30 cases of pathologically confirmed Pick's disease. Two coding mutations were identified in separate cases of Pick's disease. A glycine-to-arginine mutation at codon 389 was detected in 1 case and a lysine-to-threonine mutation at codon 257 was identified in another. Analysis of dephosphorylated tau from the brain of the patient with the codon 389 mutation revealed a prominent band representing tau, with four microtubule-binding domains and no amino terminal inserts. This is in contrast to Pick's disease without any tau gene mutations, which consist of tau with mainly three microtubule-binding domains and only a trace of tau, with four microtubule-binding domains. Functional analysis of tau with these two mutations demonstrated a reduced ability of tau to promote microtubule assembly. Surprisingly, these mutations increased tau's susceptibility to calpain I digestion, suggesting that this feature may be related to the formation of a Pick type of histology. Moreover, these data suggest that Pick's disease is not a separate entity but part of the frontotemporal dementia disease spectrum.

Adult↗
PubMed1999

Construction of a detailed physical and transcript map of the FTDP-17 candidate region on chromosome 17q21.

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is an autosomal dominant condition clinically characterized by behavioral, cognitive, and motor disturbances. Until now, at least 13 different FTDP-17 families that show linkage to chromosome 17q21 have been described. To characterize the FTDP-17 candidate region, flanked by the markers D17S1789 and D17S1804, we constructed a physical map in P1 and PAC clones. A detailed transcript map was generated by positioning known genes and EST clusters to the physical map. In total, we investigated 150 STSs mapped to this region. In addition, novel transcripts were isolated by exon-trapping. We were able to localize 19 known genes and a number of ESTs to this chromosomal region. Furthermore, seven novel genes were identified for which we isolated the full-length sequence.

Base Sequence↗
PubMed1999

No pathogenic mutations in the beta-synuclein gene in Parkinson's disease.

We present 11 families consistent with autosomal dominant inheritance of probable Parkinson's disease (PD). Although excluded as a cause of disease in these kindreds, mutations in the alpha-synuclein gene have been implicated in familial PD. The beta-synuclein gene is highly homologous, expressed in the nervous system and thus is a good candidate gene for PD. Multipoint linkage analysis was either equivocal or excluded 5q35 haplotype sharing among affected family members. Sequencing the translated exons of the beta-synuclein gene failed to identify any pathogenic mutation.

Adult↗