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Biomedical subjects

J Manson

Publications and source records attributed to J Manson.

At least 19 recordsLinked to original sources
PubMed1996

Pharmacokinetic and fetal cardiovascular effects of enalaprilat administration to maternal rhesus macaques.

OBJECTIVE: The purpose of this study was to determine the extent of placental transfer of the angiotensin-converting enzyme inhibitor enalaprilat and the effects on maternal and fetal cardiovascular parameters. STUDY DESIGN: Between gestational days 122 and 126 (term 167 days) five rhesus macaques underwent surgery for implantation of maternal and fetal vascular catheters. At least 4 days after surgery maternal and fetal blood pressures and heart rates were recorded for 1 hour. This was followed by a 5-minute maternal venous infusion of saline solution vehicle and recording for an additional hour. Enalaprilat was then infused over 5 minutes through the maternal femoral artery at doses of 0.05, 0.1, or 0.2 mg/kg. Maternal and fetal arterial blood samples were collected for determination of blood gas status and plasma enalaprilat concentrations. RESULTS: Enalaprilat rapidly crossed the placenta, and fetal values for areas under the concentration time curve were 50% to 65% of maternal values across dose groups. Drug was retained in the fetal plasma approximately threefold to fourfold longer than in maternal plasma. Maternal heart rate, blood pressure, arterial Po2 and pH were unchanged after enalaprilat infusion, as were fetal heart rate and blood gases. In contrast, fetal arterial pressure decreased significantly (19% to 23%, p < 0.01) after maternal treatment with 0.1 and 0.2 mg/kg and remained depressed throughout the 6-hour study interval. At 0.05 mg/kg fetal arterial pressure was decreased by 13% from baseline; differences were not significantly different (p > 0.05). CONCLUSIONS: Results from this study indicate that enalaprilat rapidly crosses the primate placenta with a single intravenous administration to the mother, resulting in significant and prolonged reduction of fetal arterial pressure. Because maternal cardiovascular parameters were unaffected, enalaprilat appears to have a direct effect on fetal arterial pressure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Prospective study of nutritional factors, blood pressure, and hypertension among US women.

We examined prospectively the relation of nutritional factors with hypertension and blood pressure levels among 41,541 predominantly white US female nurses, aged 38 to 63 years, who completed a detailed semiquantitative food frequency questionnaire in 1984 and were without diagnosed hypertension, cancer, or cardiovascular disease. During 4 years of follow-up, from 1984 to 1988, 2,526 women reported a diagnosis of hypertension. Age, relative weight, and alcohol consumption were the strongest predictors for the development of hypertension. Dietary calcium, magnesium, potassium, and fiber were not significantly associated with risk of hypertension, after adjusting for age, body mass index, alcohol, and energy intake. Among women who did not report hypertension during the follow-up period, calcium, magnesium, potassium, and fiber were each significantly inversely associated with self-reported systolic and diastolic pressures, after adjusting for age, body mass index, alcohol consumption, and energy intake. When the four nutrients were added simultaneously to the regression model, only fiber and magnesium intakes retained significant inverse associations with systolic and diastolic pressures. In analyses of food groups, intakes of fruit and vegetables were inversely associated with systolic and diastolic pressures, and intakes of cereals and meat were directly associated with systolic pressure. These results support hypotheses that age, body weight, and alcohol consumption are strong determinants of risk of hypertension in middle-aged women. They are compatible with the possibilities that magnesium and fiber as well as a diet richer in fruits and vegetables may reduce blood pressure levels.

Adult↗
PubMed1995

Migraine and subsequent risk of stroke in the Physicians' Health Study.

OBJECTIVE: To evaluate, in a prospective design, whether migraine is an independent risk factor for subsequent stroke. DESIGN: Evaluated as part of the Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in the primary prevention of cardiovascular disease and cancer begun in 1982. The aspirin component of the study was terminated in 1988, with average follow-up of 60.2 months. SETTING: Conducted by mail among male physicians throughout the United States. PARTICIPANTS: A total of 22,071 US male physicians aged 40 to 84 years in 1982 with no prior history of cancer or cardiovascular diseases who were enrolled in the Physicians' Health Study. INTERVENTIONS: Participants were randomized to receive 325 mg of aspirin or aspirin placebo every other day and to receive 50 mg of beta-carotene or placebo on alternate days. MAIN OUTCOME MEASURES: The primary outcomes of the Physicians' Health Study were cardiovascular disease and cancer. Because stroke was a main outcome, this provided the opportunity to evaluate the association between migraine headaches and stroke. RESULTS: Physicians reporting migraine (n = 1479) had significantly increased risks of subsequent total stroke and ischemic stroke compared with those not reporting migraine. After adjustment for age, aspirin and beta-carotene treatment assignment, and a number of cardiovascular risk factors, the relative risks were 1.84 (95% confidence interval, 1.06 to 3.20) for total stroke and 2.00 (95% confidence interval, 1.10 to 3.64) for ischemic stroke. There were too few hemorrhagic strokes in the study to evaluate this end point. No associations were seen between ordinary nonmigraine headache and subsequent stroke or between migraine and subsequent myocardial infarction or cardiovascular death. CONCLUSION: These data raise the possibility that vascular events associated with migraine may also have causative importance in stroke but require confirmation in other studies specifically designed to evaluate this question.

Adult↗
PubMed1994

Construction and characterization of a human chromosome 2-specific BAC library.

We have constructed a human chromosome 2-specific bacterial artificial chromosome (BAC) library using DNA from the somatic cell hybrid GM10826. The average size of the clones is about 63 kb. The coverage and distribution of the library were estimated by screening with known polymorphic genetic markers and fluorescence in situ hybridization (FISH). Twenty-one markers tested positive when DNA pools prepared from approximately one-sixth of the library were screened with 33 known markers. This is consistent with the theoretical calculation of 63% coverage at one genomic equivalent. This suggested that the coverage of the library is approximately 5-6x. FISH analysis with 54 BACs revealed single site hybridization to chromosome 2, and the clones were distributed randomly on the chromosome. We have also performed direct sequencing of the BAC insert ends to generate sequence-tagged sites suitable for mapping and chromosome walking. This is the first reported human chromosome 2-specific BAC library and should provide a resource for physical mapping and disease searching for this chromosome.

Base Sequence↗
PubMed1994

Does cardiovascular health mediate hearing ability?

Exercise and noise exposure causes temporary hearing loss. Yet, a direct relationship may exist between cardiovascular health and hearing. The purpose of this study was to determine whether noise and exercise caused different levels of hearing loss depending on one's cardiovascular fitness. Twenty-eight volunteers were considered: high fit VO2peak = 48.5 +/- 1.6 ml.kg-1.min-1, N = 10), moderately fit VO2peak = 38.1 +/- 0.9 ml.kg-1.min-1, N = 9), and low fit VO2peak = 30.4 +/- 0.9 ml.kg-1.min-1, N = 9). Hearing ability at 2000, 3000, and 4000 Hz was assessed following 10 min of noise (N), exercise (E), and noise-and-exercise (N&E). The high fit group consistently demonstrated better hearing after all conditions compared to the low fit group. Significant differences between the high and low fit groups always occurred during N&E and sometimes during N. E did not cause significant hearing loss in any group. Cardiovascular health as indicated by a mean VO2peak = 48.5 ml.kg-1.min-1 is associated with less hearing loss after 10 min of either N or N&E. Although the mechanisms have not been identified, these results support the existence of a cardiovascular health-hearing synergism.

Adult↗
PubMed1993

Toothfriendly.

Explore the source record for details and available documents.

Candy↗
PubMed1992

The prion protein gene: a role in mouse embryogenesis?

The neural membrane glycoprotein PrP (prion protein) has a key role in the development of scrapie and related neurodegenerative diseases. During pathogenesis, PrP accumulates in and around cells of the brain from which it can be isolated in a disease-specific, protease-resistant form. Although the involvement of PrP in the pathology of these diseases has long been known, the normal function of PrP remains unknown. Previous studies have shown that the PrP gene is expressed tissue specifically in adult animals, the highest levels in the brain, with intermediate levels in heart and lung and low levels in spleen. Prenatally, PrP mRNA has been detected in the brain of rat and hamster just prior to birth. In this study we have examined the expression of the PrP gene during mouse embryonic development by in situ hybridisation and observed dramatic regional and temporal gene expression in the embryo. Transcripts were detected in developing brain and spinal cord by 13.5 days. In addition, PrP gene expression was detected in the peripheral nervous system, in ganglia and nerve trunks of the sympathetic nervous system and neural cell populations of sensory organs. Expression of the PrP gene was not limited to neuronal cells, but was also detected in specific non-neuronal cell populations of the 13.5 and 16.5 day embryos and in extra-embryonic tissues from 6.5 days. This cell-specific expression suggests a pleiotropic role for PrP during development.

Animals↗
PubMed1991

The scrapie fibril protein and its cellular isoform.

Proteins need help to fold and attain their functional conformation (Ellis and Hemmingsen 1989), and mechanisms have evolved to prevent the accumulation of misfolded protein aggregates within cells (Pelham 1988). These mechanisms fail to prevent the formation of protease-resistant, misfolded forms of PrP (ScPrP) during the development of scrapie and other transmissible spongiform encephalopathies, and ScPrP is a biochemical marker of these diseases. Much is now known about the structure and expression of the PrP gene, but the physiological function of the PrP protein and the mechanism by which the TDE pathogen replicates and specifically interferes with PrP metabolism remain a mystery--a mystery which will entertain prion-ophiliacs for some time yet.

Animals↗
PubMed1990

Modulation of interleukin 1 beta gene expression using antisense phosphorothioate oligonucleotides.

The production of interleukin 1 beta (IL1 beta) in lipopolysaccharide (LPS) stimulated monocytes was inhibited by 98% using antisense phosphorothioate oligonucleotides complementary to the 5' untranslated and exon 6 regions of IL1 beta mRNA. A sense phosphorothioate oligonucleotide failed to inhibit IL1 beta production. The inhibition of IL1 beta synthesis was not due to reduced cell viability and [35S]methionine incorporation showed that it could not be accounted for by an overall inhibition in protein synthesis. Tumour necrosis factor (TNF) and IL1 alpha production was also inhibited but to a lesser extent than IL1 beta. The use of antisense phosphorothioate oligonucleotides to inhibit IL1 production should enable the complex pathways of IL1 regulation to be elucidated and provide information on the biological role of these cytokines.

Base Sequence↗
PubMed1988

Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years.

Two patients with infantile phytanic acid storage disease (infantile Refsum disease), one of whom showed the presence of morphologically normal peroxisomes in a liver biopsy, were treated with a low phytanic acid diet for more than 2 years and the effects of treatment on certain clinical, biochemical and ultrastructural parameters were examined. Both patients showed evidence of either an improvement or stabilisation in their clinical condition. Plasma phytanic acid levels decreased to near normal values in approximately 6 weeks after the introduction of the diet; plasma pipecolic acid also declined markedly but the decrease was not so rapid and its level remained abnormal. C26:C22 fatty acid ratios decreased very slowly and even after 2 years the values remained grossly abnormal. Despite the marked reduction of phytanic acid in the liver, there was an increase in the C26:C22 fatty acid ratios and this appeared to be paralleled by an increase in inclusion bodies. Our data suggest that some patients with the infantile form of Refsum disease may show some clinical benefit from dietary management and this is reflected biochemically by decreases in the plasma levels of phytanic acid and pipecolic acid.

Eicosanoic Acids↗
PubMed1988

Congenital blindness, porencephaly, and neonatal thrombocytopenia: a report of four cases.

Four unrelated infants with neonatal thrombocytopenia associated with congenital blindness and porencephaly have been seen over an 18-year period. The association of congenital blindness with neonatal thrombocytopenia has not previously been reported. All children had clinical purpura in the neonatal period; in three cases, thrombocytopenia was confirmed, while in one case, the diagnosis of thrombocytopenia was presumptive; in two cases, there was evidence of circulating maternal serum platelet isoantibodies. Extensive investigation for intrauterine infection was negative in the three cases with confirmed thrombocytopenia. The thrombocytopenia resolved spontaneously after the neonatal period. It is postulated that the porencephalies were the consequence of prenatal cerebrovascular episodes. The etiology of the optic atrophy is unclear. Serial cranial ultrasound investigation is recommended for all neonates with thrombocytopenia, even if neurologically asymptomatic in the neonatal period, and serial prenatal cranial ultrasound investigation is recommended for infants of mothers with a history of having previously had infants with neonatal isoimmune thrombocytopenia.

Adolescent↗
PubMed1986

Intracranial histiocytosis X: a case report.

A case of intracranial histiocytosis X that presented radiologically with thickening of the pituitary stalk is presented. The radiologic findings, including a blush seen on angiography, are described.

Adult↗
PubMed1982

Quantitative immunoassays for diagnosis and carrier detection in cystic fibrosis.

Quantitative immunoprecipitation and immunoradiometric assays have been developed for a protein present in the serum of cystic fibrosis homozygotes, and to a lesser extent in the serum of heterozygotes. When tested on a panel of sera from 14 cystic fibrosis patients, 29 heterozygotes and 23 controls, the immunoprecipitation assay allowed correct assignments to be made on 94% of occasions with one batch of antiserum and 95% with another. With the same panel of sera, the immunoradiometric assay allowed 94% correct assignments. It is suggested that such accuracy is the maximum that can be expected in the present state of knowledge of cystic fibrosis.

Blood Proteins↗
PubMed1978

Serum alphafetoprotein in cystic fibrosis of the pancreas.

Serum alphafetoprotein concentrations were measured by three different types of radioimmunoassay in 30 patients with cystic fibrosis of the pancreas and in 55 controls. The highest value obtained in cystic patient was 10.2 ng/ml and in a control 10.8 ng/ml. These are within published normal limits. Previously reported large increases in serum AFP in patients with cystic fibrosis and in heterozygote carriers have not been confirmed.

Cystic Fibrosis↗