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P Bennett

Publications and source records attributed to P Bennett.

At least 73 records · Page 4Linked to original sources
PubMed1998

Direct genetic evidence for involvement of tau in progressive supranuclear palsy. European Study Group on Atypical Parkinsonism Consortium.

OBJECTIVE: To confirm whether a dinucleotide repeat sequence in an intron of the microtubule-associated protein tau is associated with progressive supranuclear palsy (PSP) in an independent study population and to establish an improved methodology for allelotyping. BACKGROUND: It has recently been reported that a genetic variant of tau, known as the A0 allele, was represented excessively in PSP patients when compared with control subjects. METHODS: In a multicenter study, the authors examined the allelic distribution of this dinucleotide repeat marker in a set of clinically ascertained PSP patients (n = 30), multiple system atrophy (MSA) patients (n = 35), and matched control subjects (n = 70). Individuals were allelotyped using automated analysis of fluorescently labeled PCR products. RESULTS: The A0 allele was significantly overrepresented in the PSP patients (93.3% versus 76.4%; p = 0.0067; odds ratio [OR] = 4.33; 95% confidence interval [CI], 1.36 to 13.60), but not in the MSA patients. Likewise, A0 homozygotes were overrepresented in the PSP group (86.7% versus 61.1%; p = 0.02; OR = 4.14; 95% CI, 1.19 to 14.48) compared with control subjects. CONCLUSIONS: The findings of this study, which is the largest to date, support those of a previous investigation that used pathologically confirmed PSP patients. These data provide additional strong evidence that genetic variation at or near the tau gene plays an important role in the pathogenesis of PSP.

Aged↗
PubMed1997

Expression of MCH and POMC genes in rainbow trout (Oncorhynchus mykiss) during ontogeny and in response to early physiological challenges.

The expression of the neuropeptide melanin-concentrating hormone (MCH) in two groups of hypothalamic neurones (NLT- and LVR-MCH neurones), and POMC in the pituitary corticotropes and melanotropes, has been examined in rainbow trout larvae using immunocytochemistry and quantitative in situ hybridization. The aim was to establish at what stage in ontogeny these cells first respond to two physiological challenges-background color and stress. Trout reared in black or white trays showed adaptive skin pigmentary changes at 10 days posthatching, when fish in a pale environment abruptly exhibited melanin aggregation from a prior dispersed state, although the pigment cells were already competent to respond to adrenalin and MCH in vitro at 3 days. Immunoreactive MCH was detectable in the neurohypophysis at hatching and MCH mRNA in the NLT-MCH neurones (which project to the pituitary) was enhanced at 7 days in the white-reared trout. Immunostainable POMC was also present in the pars intermedia at hatching but their POMC mRNA was unaffected by tank color until 28 days, when it was enhanced in the black-reared trout. It is suggested that early pigment concentration depends on neural signals from the sympathetic nervous system in conjunction with MCH from the NLT rather than on a reduction in alphaMSH secretion from the pars intermedia. MCH mRNA in the LVR-MCH neurones was increased on a pale environment only 28 days after hatching, suggesting that these cells play little role in the early adaptive pigment response. Previous studies on the ontogeny of cortisol secretion indicate the hypothalamopituitary-interrenal axis can respond to stress by about 14 days. However, the pituitary ACTH cells showed no stress-induced changes in POMC mRNA until 28 days. ACTH release may therefore be dissociated from POMC transcription in the early stages of development. The LVR- and NLT-MCH neurones were both stimulated by stress, LVR-MCH mRNA responding by 14 days and NLT-MCH mRNA by 21 days. Melanotrope POMC mRNA was reduced by stress but the physiological significance of this is not known.

Aging↗
PubMed1997

Inhibition of intermediate-term memory following passive avoidance training in neonate chicks by a presynaptic cholinergic blocker.

The effects of a specific presynaptic cholinergic antagonist, toosendanin, on memory formation following a passive avoidance training experience in day-old chicks was investigated. Bilateral injection of toosendanin into the neostriatal/hyperstriatal region of the chick forebrain produced memory impairment in a dose-dependent manner. Retention deficits were apparent from 20 min following training in chicks treated with toosendanin, regardless of the injection time relative to training. Chicks that received injections of the drug at corresponding times prior to retention tests showed normal retention levels, suggesting that toosendanin has no effect on performance and memory retrieval. These results indicate an involvement of cholinergic transmission during an early stage of memory formation.

Acetylcholine↗
PubMed1997

Health locus of control and value for health in smokers and nonsmokers.

A representative sample of 11,401 persons completed a questionnaire, including measures of health locus of control, value for health, and smoking frequency. Smokers held stronger internal, chance, and powerful others beliefs than never smokers. Ex-smokers had lower scores on internal and chance dimensions and placed a higher value on their health than smokers. The interaction between chance health locus of control and value for health was a significant predictor of smoking status, suggesting that health value may moderate the relationship between health locus of control and smoking status. Within smokers, the health locus of control dimensions and value for health explained less than 1% of the variance in smoking frequency, with only the chance dimension emerging as a significant predictor.

Adolescent↗
PubMed1997

Human cysteine dioxygenase type I (CDO-I; EC 1.13.11.20): 5' flanking region and intron-exon structure of the gene.

AIM: The elucidation of the structure of the 5' flanking region and the exonic organisation of the human cysteine dioxygenase type I gene. METHODS: Material for sequence studies was generated by polymerase chain reaction (PCR) methods using human genomic DNA, a cosmid clone containing the entire gene, and a commercial gene walking kit. RESULTS AND CONCLUSIONS: The gene was found to be--12 kb in length and made up of five exons (418, 78, 155, 170, and 731 base pairs, respectively). The immediate 5' flanking region did not contain the canonical TATAA box. One DNA source (Clontech promoter finder kit) contained a liver specific nuclear factor response element approximately 550 base pairs from the transcription start site, whereas a second source did not. This and other cis acting factors in the 5' flanking region were identified by computer analysis. The physiological significance of such elements requires detailed experimental evaluation.

Base Sequence↗
PubMed1997

Intrahypothalamic growth hormone feedback: from dwarfism to acromegaly in the rat.

Two different dwarf rat models with primary (dw/dw, DW) or secondary (transgenic growth retarded, WF/Tgr) GH deficiency and contrasting hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIH) expression were implanted sc with GC cells. These form encapsulated rat GH-secreting tumors that maintain high plasma rat GH levels for several weeks. In both strains, GC cell tumors stimulated growth and raised GHBP levels, without affecting pituitary GH content. In DW rats, GC cell implants increased SRIH expression in the periventricular nucleus (PeV), but not in the arcuate nucleus (ARC), whereas their high GHRH expression in ARC was decreased by GC cells. In contrast, GC cell implants in WF/Tgr rats had little effect on the already high SRIH expression in PeV or low GHRH expression in ARC, although they reduced SRIH expression in ARC. GC cell implants also reduced GH receptor expression in both ARC and PeV in the WF/Tgr dwarves. Thus, chronic GH overexposure stimulates rapid growth in both dwarf strains, but has differential hypothalamic effects in these models. This experimental approach now makes it possible to study the effects of pathophysiological concentrations of GH ranging from dwarfism to acromegaly in the same animal model.

Acromegaly↗
PubMed1996

Central administration of a growth hormone (GH) receptor mRNA antisense increases GH pulsatility and decreases hypothalamic somatostatin expression in rats.

To test the hypothesis of the involvement of centrally expressed rat growth hormone receptors (rGH-R) in the ultradian rhythmicity of pituitary GH secretion, adult male rats were submitted to a 60 hr intracerebroventricular infusion of an antisense (AS) oligodeoxynucleotide (ODN) complementary to the sequence of rGH-R mRNA. Eight hour (10 A.M.-6 P.M.) GH secretory profiles, obtained from freely moving male rats infused with 2.0 nmol/hr of rGH-R AS, revealed a marked increase in GH peak amplitude (150 +/- 12 vs 101 +/- 10 ng/ml), trough levels (16.2 +/- 3.0 vs 5.4 +/- 1.4 ng/ml), and number of peaks (2.9 +/- 0.3 vs 1.8 +/- 0.2). No change was observed in rats treated with an ODN complementary to the prolactin receptor mRNA sequence (2.0 nmol/hr). Infusion of increasing ODN concentrations resulted in a dose-dependent stimulation of GH release. In parallel, somatogenic binding sites in the choroid plexus were decreased by 40%, and levels of rGH-R mRNA were increased in the periventricular nucleus (PeV) but unchanged in the arcuate nucleus (ARC). Levels of somatostatin mRNA, in the PeV but not in the ARC, were lowered by the treatment. Levels of GH-releasing hormone mRNA in the ARC were not affected. These data suggest that GH negative feedback results from a direct effect on central GH receptors and a subsequent activation of hypophysiotropic somatostatin neurons located in the anterior periventricular hypothalamus.

Animals↗
PubMed1996

No association between Parkinson's disease and low-activity alleles of catechol O-methyltransferase.

Idiopathic Parkinson's disease (IPD) is characterised by the loss of pigmented neurones in the substantia nigra, leading to reduced tyrosine hydroxylase activity and depletion of dopamine. Treatments attempt to correct this deficit by the use of levodopa and inhibitors of dopamine metabolising enzymes such as catechol-O-methytransferase (COMT). A common amino-acid polymorphism in COMT, valine-108-methionine, results in a low activity form of the enzyme which we hypothesised may influence susceptibility to IPD. We examined this polymorphism in 139 Caucasian subjects with IPD and 173 control subjects, using a PCR-RFLP and a novel Amplification Refractory Mutation System (ARMS) assay. Allele and genotype frequencies were similar in the affected and control subjects, indicating that variation of COMT activity is not an aetiological factor in IPD. We have also characterised a new polymorphism, 256C/G, which is not associated with IPD. However it remains possible that allelic variation in COMT influences severity, type of pathology or treatment response to levodopa or COMT inhibitors.

Alleles↗
PubMed1996

[Prognostic markers for weight loss in the treatment of obesity].

The aim of the study was to identify prognostic metabolic markers for long-term weight loss outcome in obese women. Forty female obese patients underwent a dietary intervention of 36 weeks treatment with a 4.2 MJ/d low-fat high carbohydrate diet and were followed-up two and a half years after cessation of treatment. The maximum weight loss (mean 16.2 kg. 95% CI 14.2-18.2) was positively associated to pre-treatment 24-h energy expenditure (EE) (p < 0.01), fat oxidation (%) (p < 0.02), plasma dihydrotestosterone (DHT) (p < 0.01), and to postprandial noradrenaline concentration (p < 0.04). Together these factors could explain 41% of the variation in maximum weight loss. After 36 weeks only 24-h EE and DHT had predictive power on weight loss. Weight losses in upper and lower tertiles of DHT concentrations were 17.7 kg (14.1-21.4) and 9.8 kg (6.2-13.3) (p < 0.02) and the adjusted relative risk of losing < 10 kg in the upper compared to the lower DHT tertile was 12% (4-32%). At two and a half years follow-up 21 patients had maintained some of the weight loss (54%), while 14 patients had maintained > 5 kg weight loss (36%). High levels of pre-treatment DHT were also associated with better weight loss at two and a half years follow-up. The study suggests that long-term weight loss outcome may be predicted by pre-treatment metabolic and hormonal factors in obese women.

Adolescent↗
PubMed1996

Case report: uniparental disomy 16 in association with congenital heart disease.

Uniparental disomy (UPD) is the inheritance of both copies of a given chromosome from the same parent (Warburton, 1988; Anon., 1991). The exact disease associations of UPD of individual chromosomes have yet to be fully elucidated and the question of whether UPD of some chromosomes may be regarded as a benign finding remains unanswered. We report an infant with uniparental maternal disomy 16, the only such infant identified at King's College Hospital. The infant had intrauterine growth retardation and minor congenital heart disease.

Adult↗
PubMed1996

The involvement of Ca2+/calmodulin-dependent protein kinase in memory formation in day-old chicks.

Day-old chicks trained on a single trial passive avoidance learning task showed a significant increase, relative to untrained controls, in activity of the Ca2+/calmodulin-dependent protein kinase (CaMK) in the particulate fraction from tissues from the intermediate medial hyperstriatum ventrale region of the forebrain. The increased kinase activity was observed within 10 min following training and persisted for at least 70 min posttraining. Amnesia for the task was induced by micromolar concentrations of the specific CAMK II antagonist, KN-62, administered into the neostriatal/hyperstriatal region of the forebrain. The effect of KN-62 was lateralized. In the right hemisphere, KN-62 induced amnesia only when injected within 2. 5 min following training, with memory loss evident by 5 min posttraining. In contrast, in the left hemisphere amnesia was induced by KN-62 administered as late as 5 min posttraining, with onset of amnesia occurring after 10 min posttraining. The findings were interpreted within the context of a three-stage model of memory formation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Molecular genetic etiology of twin reversed arterial perfusion sequence.

OBJECTIVE: Our purpose was to determine whether the twin reversed arterial perfusion sequence (acardiac anomaly) results from fertilization of the first or second polar body. STUDY DESIGN: Placental or fetal tissue was obtained from nine twin sets discordant for twin reversed arterial perfusion. After deoxyribonucleic acid extraction, the polymerase chain reaction was used to amplify five polymorphic microsatellite repeats. The products were differentiated by polyacrylamide gel electrophoresis, and patterns were compared within twin sets. RESULTS: Deoxyribonucleic acid fingerprinting patterns were identical in all twin sets for all primer pairs. It is calculated that the chance that any of the acardiac twins resulted from fertilization of either the first or second polar body is <4% and the chance that they all resulted from polar body fertilization is <0.001%. CONCLUSION: Twins discordant for the twin reversed arterial perfusion sequence anomaly are monozygous. Our results exclude polar body fertilization as a likely cause of this condition.

Autoradiography↗
PubMed1996

Cancer detection activities coordinated by nursing students in community health.

This article describes ongoing cancer screening in a low-income and ethnically diverse community (primarily Southeast Asian and Hispanic). These services are part of the comprehensive care provided in a district nursing community health clinical. Screening services occur within the refugee community and include mammograms, individualized breast self-exam (BSE) teaching, home follow-up on the BSE teaching, and assistance obtaining any additional screening or treatment, if necessary. Except for technician activities, students plan, implement, and evaluate all services. The first event was in spring 1995, the second in summer 1995, and the third in fall 1995. Thus far, 85 women have received services. Cambodian and Laotian women show the lowest level of knowledge and experience related to breast cancer detection. This article provides some of the first data on cancer screening for low-income Cambodian and Laotian women in the United States. The article also shows how ongoing cancer screening and prevention services can be provided to populations that have not been successfully reached through usual means, e.g., referral by nurse practitioner, physician, and electronic or print media. Specific means of overcoming barriers to screening, prevention, and learning are described in detail.

Breast Neoplasms↗
PubMed1996

Complete structural characterisation of the human aryl hydrocarbon receptor gene.

Aims-To clone and characterise the complete structural gene for the human aryl hydrocarbon receptor (AhR). This gene, located on chromosome 7, encodes a cytosolic receptor protein which, upon activation by various xenobiotic ligands, translocates to the nucleus, where it acts as a specific transcription factor.Methods-Primers, based on the AhR cDNA sequence, were used in conjunction with recently developed long range PCR techniques to amplify contiguous sections of the cognate gene. The amplicons produced were then cloned and characterised. A cDNA probe was also used to screen a human P1 library.Results-Using the cDNA primers, DNA fragments which mapped the entire coding region of the gene were amplified and cloned. All but one of these fragments were amplified directly from human genomic DNA. The remaining fragment was amplified using DNA prepared from a P1 clone as the PCR template. This P1 clone, obtained by screening a human P1 library, also contained the entire Ah locus. Characterisation of amplified and cloned DNA fragments provided sufficient information for the construction of a complete structural map of the gene. This also included 150 base pairs of nucleotide sequence data at all intronic termini.Conclusions-These data indicate that the human AhR gene is about 50 kilobases long and contains 11 exons. The overall intron/exon structure of the human gene is homologous to that of the previously characterised mouse gene; however, it is probably some 20 kilobases larger. These results demonstrate the need for further characterisation and provide the data to facilitate this.

Journal Article↗