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Biomedical subjects

M White

Publications and source records attributed to M White.

At least 163 records · Page 9Linked to original sources
PubMed1998

Detection of translocations involving the Y-chromosome in prospective prenatal screening of common chromosomal aneuploidies by FISH.

In the application of the fluorescence in situ hybridization (FISH) technique for prospective prenatal screening of common aneuploidies involving the autosomes 13, 18, and 21, and sex chromosomes, six cases of inconsistency between the results of FISH analysis and the results of karyotyping of cultured amniocytes have been observed, including two cases of translocation involving the Y-chromosome and chromosome 15 in a total of 904 cases of amniocentesis studied. In one case, the translocation was of maternal origin, and in the other, of paternal origin. In both cases, the couples decided to continue the pregnancy and normal babies were delivered. The data show the usefulness of applying the FISH technique in prospective prenatal screening of common trisomies for the possible detection of rare chromosome rearrangements involving the Y-chromosome.

Aneuploidy↗
PubMed1998

Physician-assisted suicide: reflections on Oregon's first case.

The authors analyze Oregon's first reported assisted suicide of Mrs. A as a real life application of the Oregon Death with Dignity Act. They critique the effectiveness of the Act's safeguards as illustrated by the case of Mrs. A. They point out that the Act does not require that physicians be adequately trained in palliative care in order to participate in assisted suicide. Most physicians do not have such training. Without it, they are not able to effectively present alternatives to patients requesting assisted suicide. Most physicians also lack the expertise to assess patients' decision-making capacity. Nor does the Act ensure that physicians will be in a position to assess coercion of patients' decisions. The Act requires physicians to report only minimal information about their cases, and there are no enforcement provisions to see that even this is done. Under the Act, a good faith standard rather than the more usual negligence standard immunizes physicians from civil or criminal liability even when they act negligently. The authors demonstrate that the Act protects physicians more than patients, and encourages secrecy. The authors conclude that secrecy will need to be replaced by openness to permit the kind of examination the practice of assisted suicide warrants.

Confidentiality↗
PubMed1997

Serum concentrations of vitamins A and E in impaired glucose tolerance.

Serum concentrations of vitamins A and E were measured in 32 subjects with impaired glucose tolerance (IGT) and 148 subjects with normal glucose tolerance using reversed-phase high-performance liquid chromatography. Fasting glucose, insulin and lipid concentrations were also measured. Serum vitamin A concentrations were higher in subjects with IGT 2.5 (1.1-3.4) vs. 2.1 (1.4-3.2) mumol/l [median (2.5-97.5 percentiles)] (P = 0.002), the difference remaining significant after adjustment for triglycerides (P = 0.028). There was a univariate association between vitamin A levels and insulin resistance (r = 0.164; P = 0.02) and in multivariate logistic regression analysis the relative risk of subjects with high vitamin A concentrations having IGT was 3.8 (P = 0.002). There were no differences in serum vitamin E concentrations between the groups. These data suggest that higher vitamin A concentrations found in non-insulin-dependent diabetes pre-date the onset of diabetes. Further studies are required to confirm this finding and to investigate the possibility of a role for vitamin A in the aetiology of diabetes and IGT.

Blood Glucose↗
PubMed1997

Protein binding and signaling properties of RIN1 suggest a unique effector function.

Human RIN1 was first characterized as a RAS binding protein based on the properties of its carboxyl-terminal domain. We now show that full-length RIN1 interacts with activated RAS in mammalian cells and defines a minimum region of 434 aa required for efficient RAS binding. RIN1 interacts with the "effector domain" of RAS and employs some RAS determinants that are common to, and others that are distinct from, those required for the binding of RAF1, a known RAS effector. The same domain of RIN1 that binds RAS also interacts with 14-3-3 proteins, extending the similarity between RIN1 and other RAS effectors. When expressed in mammalian cells, the RAS binding domain of RIN1 can act as a dominant negative signal transduction blocker. The amino-terminal domain of RIN1 contains a proline-rich sequence similar to consensus Src homology 3 (SH3) binding regions. This RIN1 sequence shows preferential binding to the ABL-SH3 domain in vitro. Moreover, the amino-terminal domain of RIN1 directly associates with, and is tyrosine phosphorylated by, c-ABL. In addition, RIN1 encodes a functional SH2 domain that has the potential to activate downstream signals. These data suggest that RIN1 is able to mediate multiple signals. A differential pattern of expression and alternate splicing indicate several levels of RIN1 regulation.

3T3 Cells↗
PubMed1997

Preimplantation diagnosis of single gene disorders by two-step oocyte genetic analysis using first and second polar body.

Previous work on preimplantation genetic diagnosis (PGD) of single gene disorders by the first polar body (IPB) analysis has demonstrated that the genotype of a considerable number of embryos resulting from heterozygous oocytes cannot be predicted without testing their second PB (IIPB). To overcome this limitation we introduce a two-step DNA analysis of oocytes using both IPB and IIPB to identify hemizygous mutation-free oocytes following the second meiotic division. In the application of the approach to PGD of cystic fibrosis (CF) Delta F-508 mutation, sickle cell disease, and hemophilia B, 80 oocytes were studied by both PBs, resulting in the identification and transfer of 32 homozygous normal embryos. A follow-up genotyping of 52 embryos, resulting from oocytes tested by both IPB and IIPB demonstrated the accuracy of the predicted genotypes. In addition to a nested PCR analysis of the mutant genes in PBs and resulting embryos, simultaneous amplification of different polymorphic markers was performed, demonstrating the reliability of the two-step polar body analysis of oocytes.

Alleles↗
PubMed1997

Effects of chromium on lymphocyte subsets and immunoglobulins from normal population and exposed workers.

Blood lymphocyte subsets and serum immunoglobulins were studied in 15 men (mean age: 35 years), not exposed to toxic agents, and in 15 healthy men, exposed to dust containing several compounds (including lead chromate), working in a factory producing plastic materials. Worker blood lead and urine chromium (Cr) levels were significantly higher than controls, while serum Cr concentration was unchanged. In the worker blood, CD4+ helper-inducer (mainly CD4+-CD45RO- "virgin"), CD5--CD19+ B, CD3--CD25+ activated B and CD3--HLA-DR+ activated B and natural killer (NK) lymphocytes were significantly reduced (about 30-50 %). The investigated workers were exposed to hexavalent Cr, as lead chromate, whereas normal population (control group) was mainly exposed to trivalent Cr. In the control group, urinary Cr showed a significant positive correlation with CD16+-56+ NK, CD5+-CD19+ B and HLA-DR+ activated T, B and NK lymphocytes and a negative correlation with serum IgA immunoglobulins; moreover, serum Cr was significantly correlated with all blood lymphocytes and HLA-DR+, CD3--HLA--DR+ and CD3--CD25+ lymphocyte subsets. These data suggest that trivalent Cr may be involved in mechanisms regulating the immune response in humans.

Adult↗
PubMed1997

Restoration of thymocyte development and function in zap-70-/- mice by the Syk protein tyrosine kinase.

The Syk family of protein tyrosine kinases, consisting of ZAP-70 and Syk, associate with the pre- and alphabeta T cell antigen receptors (TCRs) and undergo tyrosine phosphorylation and activation following receptor engagement. Thymocyte development in zap-70-/- mice is blocked at the CD4+CD8+ TCR(lo) stage. The presence of Syk in the thymus has raised the possibility that Syk may be able to mediate TCR function. To determine if Syk can play a role in thymocyte development, we generated zap-70-/- mice expressing a human syk cDNA. Syk expression restored both thymocyte development and function. In addition, Syk function required the CD45 transmembrane protein tyrosine phosphatase. Hence, ZAP-70 and Syk can play overlapping functions and exhibit similar regulatory mechanisms in mediating alphabeta T cell development.

Animals↗
PubMed1997

Second- and third-generation beta-blocking drugs in chronic heart failure.

The left-ventricular (LV) functional, hemodynamic, and antiadrenergic effects of metoprolol, bucindolol, and carvedilol have been compared in three concurrent placebo-controlled clinical trials in patients with symptomatic idiopathic dilated cardiomyopathy. All three drugs were well tolerated, all produced at least moderate degrees of beta-blockade as assessed by reduction in exercise heart rate, and all increased the left-ventricular ejection fraction. Compared with the beta 1-selective, second-generation compound metoprolol, the third-generation compounds bucindolol and carvedilol lowered indices of adrenergic activity and tended to improve LV function to a greater extent. In patients with chronic heart failure there may be important therapeutic response differences between second- and third-generation beta-blocking agents.

Adrenergic beta-Antagonists↗
PubMed1997

Age- and gender-related changes in endothelin and catecholamine release, and in autonomic balance in response to head-up tilt.

1. There is an increase in circulating levels of vasoconstrictive hormones and an alteration in baroreceptor responsiveness with aging. The role of changes in endothelium-dependent and -independent vasoconstrictive hormones in relation to age and gender, with simultaneous assessment of autonomic balance in response to head-up tilt, has been incompletely studied. 2. Sixteen young [25 +/- 3 years (mean +/- SEM)] and 16 older normal volunteers (68 +/- 7 years) underwent a 30 min head-up tilt test at 60 degrees. Haemodynamics were measured every 5 min and blood samples for neurohormone measurement were drawn at baseline, 5, 10, 15 and 30 min into the test. Heart rate variability was analysed in 5 min segments at the baseline, and during the test. The younger subjects exhibited a greater increase in heart rate and diastolic blood pressure, despite lower absolute levels of noradrenaline (norepinephrine) and endothelin-1. Analysis of heart rate variability yielded a decrease in both high- and low-frequency bands in the aged; power at low-frequency decreased only in the young subjects. The age-related differences in blood pressure and noradrenaline levels were markedly attenuated in the female subjects. In addition, endothelin-1 levels and power spectral measurements at low frequency were the lowest in younger females throughout the tilt. 3. Despite attenuated cardiovascular response to tilt, both systemic adrenergic 'drive' and endothelin-1 levels increase in parallel with aging. Thus, endothelium-dependent and -independent vasoconstrictive hormone levels increase with age in the resting state and in response to neurohumoral stimulation in humans.

Adult↗
PubMed1997

Effects of age on cardiovascular responses to adrenaline in man.

AIMS: Whereas the effects of ageing on beta-receptor mediated responses have been extensively studied in vitro and in vivo using the beta-adrenoceptor agonist isoprenaline, little is known regarding ageing induced changes in responses to endogenous catecholamines. In the present study, we assessed age-related changes in cardiac responses to the endogenous beta-adrenoceptor agonist adrenaline and the influence of age-related changes in arterial baroreflex function on these responses. METHODS: Adrenaline alone was infused in 14 young subjects, age 30 +/- 2 years (eight males, six females), and 18 older subjects (six males, 12 females), age 60 +/- 2 years, and together with ganglionic blockade (trimetaphan) in seven young and 11 older subjects. Adrenaline was infused at 3-4 incremental rates, each rate for 8 min. Cardiac function was assessed by echocardiography. RESULTS: Adrenaline alone, at infusion rates 20-160 ng kg-1 min-1 caused similar increases in heart rate in the two groups. In contrast, adrenaline caused larger increases in stroke volume, ejection fraction, cardiac index and systolic blood pressure and larger decreases in end-systolic wall stress and diastolic blood pressure in the young compared with older subjects. Older females exhibited the smallest increases in stroke volume index and ejection fraction. With concomitant ganglionic blockade, all above cardiovascular responses to adrenaline were similar in the young and older group. Plasma adrenaline increased similarly in the two groups. CONCLUSIONS: We conclude that ganglionic blockade does not unmask an age-related decrease in cardiovascular responses to adrenaline (in contrast to isoprenaline). A concomitant ageing induced decrease in neuronal uptake (which applies to adrenaline, but not isoprenaline) may explain such a differential effect.

Adrenergic beta-Agonists↗
PubMed1997

International Conference for the Development of a Consensus on the Management and Prevention of Severe Candidal Infections.

Because of the rapidly increasing incidence of serious candidal infections, a consensus conference of 22 investigators from the United States, Europe, and Japan was held to discuss strategies for the prevention and treatment of deep-organ infections caused by Candida species. Commonly asked questions concerning the management of candidal infections were selected for discussion by the participating investigators. Possible answers to the questions were developed by the investigators, who then voted anonymously for their preferences. In certain instances, unanimity or a strong consensus was the result. In all cases, the full spectrum of responses was recorded and is presented in this report. The forms of candidal infection addressed included candidemia, candiduria, hepatosplenic candidiasis (chronic systemic candidiasis), candidal endophthalmitis, and candidal peritonitis. Prevention and treatment strategies were considered for patients who have undergone surgery, for neutropenic and nonneutropenic patients, and for patients who have undergone bone marrow and solid organ transplantation. The therapeutic roles of amphotericin B (standard and lipid formulations) and the azoles were considered.

Animals↗