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Biomedical subjects

L R White

Publications and source records attributed to L R White.

At least 73 records · Page 4Linked to original sources
PubMed1996

Pulmonary function measures as predictors and correlates of cognitive functioning in later life.

The relation between pulmonary function and cognitive functioning was investigated in a cohort of 3,036 Japanese-American men living in Hawaii. Pulmonary function, as indicated by forced expiratory volume in 1 second (FEV1), was measured at the baseline examination from 1965 to 1968. Cognitive function was assessed by the Cognitive Abilities Screening Instrument (CASI) test at least 23 years later (1991-1993). Baseline FEV1 was significantly correlated with follow-up CASI score (r = 0.22, p = 0.0001). Although the strength of the association was reduced by controlling for the effects of other factors, stepwise multiple linear regression showed that FEV1 during middle age was a significant predictor of CASI in later life, after taking into account the effects of age, education, stroke, sedentary job activity, nonmanual occupation, height, generation, and Japanese speaking ability. The mean CASI value was significantly greater for men whose FEV1 exceeded 2.8 liter compared with those whose FEV1 levels were in the lowest (<2.5 liters) quartile. Furthermore, the test on the effect of interaction between FEV1 and age was statistically significant (p = 0.0024), with subjects less than 55 years of age at the baseline examination showing a stronger direct association of FEV1 with CASI than the men aged 55 or older. These findings suggest that pulmonary function impairment may be associated with cognitive function impairment in later life.

Aged↗
PubMed1996

MRS study of glutamate metabolism in cultured neurons/glia.

[U-13C]Glutamate metabolism was studied in primary brain cell cultures. Cell extracts as well as redissolved lyophilized media were subjected to nuclear magnetic resonance spectroscopy in order to identify 13C labeled metabolites. Both neurons and astrocytes metabolized glutamate extensively with 13C label appearing in aspartate in all cultures. Additionally, GABA is synthesized in the GABAergic cortical neurons. Labeling of lactate and glutamine was prominent in medium from astrocytes, but not detectable in cerebral cortical neurons. Cerebellar granule neurons showed some labeling of lactate. Glutamate derived from the first turn of the tricarboxylic acid cycle (1,2,3-13C3-isotopomer) is present in all cell types analyzed. However, glutamate derived from the second turn of the cycle was only detected in granule neurons. In astrocytes, the transaminase inhibitor aminooxyacetic acid not only abolished the appearance of aspartate, but also of the 1,2,3-13C3-isotopomer of glutamate, thus showing that transamination is necessary for the conversion of 2-oxoglutarate to glutamate. The entry of glutamate into the tricarboxylic acid cycle was, however, not seriously impaired. 3-nitropropionic acid abolished the appearance of aspartate, the 1,2,3-13C3-isotopomer of glutamate and lactate in cerebellar granule neurons.

Animals↗
PubMed1996

Relaxation of human temporal artery by endothelin ETB receptors.

Endothelin receptors have been characterized in human temporal artery by molecular biological methods and in vitro pharmacology. Reverse transcriptase-polymerase chain reaction was used to detect mRNA encoding ETA and ETB receptors in normal and endothelium-denuded arteries. Vasomotor response experiments with a specific ETA antagonist (FR 139317) suggested the presence of ETA subtypes. Marked ETB-mediated relaxation was obtained with ET-3 when ETA activity was blocked in precontracted arteries. Relaxation was significantly reduced by bosentan, indomethacin, and a nitric oxide synthase inhibitor. It may be speculated that the relaxant activity is mediated through ETB1 receptors.

Azepines↗
PubMed1996

Protein kinase C inhibitors and PAF stimulate phosphatidylserine synthesis in human leucocytes.

To study the regulation and turnover of phosphatidylserine (PtdSer) in human leucocytes, we investigated the effect of 12-O-tetradecanoylphorbol 13-acetate (TPA), I-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3 or edelfosine), staurosporine and platelet activating factor (PAF) on [14C]serine incorporation into phospholipids. More than 80% of lipid radioactivity was in PtdSer. ET-18-OCH3 stimulated incorporation into PtdSer 5-fold, without increasing incorporation into other lipids. PAF stimulated PtdSer synthesis 3-fold after 1 h, while staurosporine stimulated the synthesis 2-fold after 3 h. TPA inhibited PtdSer synthesis. It abolished the ET-18-OCH3 stimulation, and reduced the staurosporine stimulation. ET-18-OCH3 and TPA did not significantly alter the incorporation of [14C]arachidonic acid into PtdSer, and did not increase PtdSer turnover judged from chase and stability experiments. The results demonstrate that PKC inhibitors and PAF induce increased incorporation of [14C]serine into PtdSer, while TPA inhibits stimulated PtdSer synthesis. This suggests that modulation of PtdSer synthesis may regulate PKC activity in PMN cells.

Antineoplastic Agents↗
PubMed1996

Vasoactivity mediated by endothelin ETA and ETB receptors in isolated porcine ophthalmic artery.

Endothelin isopeptides and sarafotoxin S6b induced strong contractions in isolated porcine ophthalmic artery at basal tension, which were antagonized in a concentration-dependent manner by the specific ETA antagonist FR 139317. The maximum contraction and potency of endothelin-1 and sarafotoxin S6b were similar, whereas endothelin-3 was significantly less potent and induced weaker contractions. Schild plot analysis was only obtained for endothelin-1 and sarafotoxin S6b, but indicated competitive binding at the same ETA receptor site for these peptides. However, the slope obtained for endothelin-1 was significantly less than unity, suggesting more than one receptor. FR 139317 was a more potent antagonist of contractions induced by endothelin-3 than the other peptides. In arteries pre-contracted by prostaglandin F2 alpha high endothelin-3 concentrations induced additional contraction, except in the presence of FR 139317 when a marked relaxation was observed, an ability which was otherwise marked by the strong contractile activity. The relaxation was significantly reduced in endothelin-denuded segments. Both contraction and relaxation were abolished by the ETA/B antagonist bosentan. The results suggest the presence of ETB as well as ETA receptors in this artery type, though ETB receptor activity is only demonstrated at an unusually high concentration of endothelin in this preparation in vitro.

Animals↗
PubMed1996

Epidemiologic observations on Parkinson's disease: incidence and mortality in a prospective study of middle-aged men.

We determined age-specific and age-adjusted incidence rates and mortality rates of idiopathic Parkinson's disease (PD) in a cohort of men followed for 29 years. Since enrollment in 1965, the Honolulu Heart Study has followed 8,006 American men of Japanese or Okinawan ancestry. Rescreening of the entire cohort, completed in 1994, included attempts to detect all prevalent and incident cases of PD, parkinsonism, and related conditions. PD incidence rates and age-incidence patterns were similar to rates previously published for Caucasian men in Europe and the United States, and were higher than incidence rates published for Asian men living in Asian nations. Prevalence patterns appeared to correspond more closely to patterns observed in developed nations than in Asian nations. PD was associated with markedly increased mortality that appeared to result from effects of both absolute age and disease duration. There was no firm evidence for differences in birth cohort risks of PD. These data may have implications for maturational and environmental theories of PD etiology.

Aged↗
PubMed1996

Case-control study of idiopathic Parkinson's disease and dietary vitamin E intake.

A nested case-control study of 84 incident cases of patients with idiopathic Parkinson's disease (PD) detected by June 30, 1994 and 336 age-matched control subjects, compared previously-documented intake of total dietary vitamin E and of selected vitamin E-containing foods. All study subjects had been followed for 27 to 30 years after diet recording in the 8,006-man Honolulu Heart Study cohort. We determined PD outcomes by periodic cohort re-examination and neurologic testing, private physician reports, examination of O'ahu neurologists' office records, and continual death certificate and hospital discharge diagnosis surveillance. Data on vitamin E intake, obtained from three dietary data sets at the time of cohort enrollment (1965 to 1968), included a food-frequency questionnaire and a 24-hour photograph-assisted dietary recall administered by trained dietitians. Although absence of PD was significantly associated with prior consumption of legumes (adjusted OR = 0.27, 95% CI 0.09 to 0.78), a dietary variable preselected for high vitamin E content, neither food categories nor quartiles nor continuous variables of vitamin E consumption were significantly associated with PD occurrence. Though consistent with prior reports of PD protection afforded by legumes, and with speculation on the possible benefits of dietary or supplemental vitamin E in preventing PD, these preliminary data do not conclusively document a beneficial effect of dietary vitamin E on PD occurrence.

Aged↗
PubMed1995

Vasodilation in porcine ophthalmic artery: peptide interaction with acetylcholine and endothelial dependence.

Co-activation of cranial perivascular sensory and parasympathetic fibres in vivo induces simultaneous release of several vasodilatory substances with neurotransmitter or neuromodulatory roles. The role of the endothelium and possible interactions between such substances are poorly understood. The objective of this study was therefore to investigate these aspects with the sensory dilator calcitonin gene-related peptide (CGRP) and the parasympathetic dilators acetylcholine (ACh) and vasoactive intestinal peptide (VIP) in isolated porcine ophthalmic artery. Whilst ACh induced relatively rapid, endothelium-dependent dilation, CGRP and VIP induced slower dilations. Both CGRP and VIP were found to have partial endothelium-dependence in this artery. The simultaneous addition of ACh with CGRP potentiated the relaxation induced by CGRP, as has already been shown for substance P. ACh did not potentiate VIP relaxation, but the results generally indicate a potential role for ACh in initiating rapid dilation prior to strong, sustained relaxation by CGRP or VIP. The potential role of the endothelium and of substances like ACh or substance P in enhancing the rate of dilation of neuropeptides inducing strong and sustained relaxation is discussed.

Acetylcholine↗
PubMed1995

Large-scale expression, purification and characterization of small fragments of thrombomodulin: the roles of the sixth domain and of methionine 388.

Fragments of human thrombomodulin (TM) have been expressed in large quantities in the Pichia pastoris yeast expression system and purified to homogeneity. Fermentation of P. pastoris resulted in yields of 170 mg/l TM. Purification to homogeneity resulted in an overall 10% yield, so that quantities of approximately 20 mg purified fragments can be readily obtained. Smaller fragments of TM, such as the individual fourth or fifth domains, were not active, nor were equimolar mixtures of the two domains. These results demonstrate that the fourth and fifth epidermal growth factor (EGF)-like domains together comprise the smallest active fragment of TM. The fragment containing the fourth and fifth EGF-like domains [TMEGF(4-5)] had 10% the specific activity of rabbit TM. Comparison of the M388L mutant TMEGF(4-5) fragment with the same mutant TMEGF(4-5-6) fragment showed that the fragment with the sixth domain had a 10-fold better Km value for thrombin than the fragment that did not contain the sixth domain; this factor completely accounts for the higher specific activity of the fragments containing the sixth domain. Comparison of the wild-type and M388L mutants showed that the M388L mutation resulted in a 2-fold increase in kcat for the activation of protein C by the thrombin-TM fragment complex, completely accounting for the 2-fold increase in specific activity of these mutant fragments.

Amino Acid Sequence↗
PubMed1995

Respiratory studies in SUNCT syndrome.

Seven SUNCT patients (six men, one woman) took part in this study. In four patients, respiratory variables were compared during and outside attacks. In five patients, peripheral chemosensitivity was tested and compared with a control group matched with respect to age, sex, and smoking habits. The results indicate that SUNCT patients hyperventilate during attacks. Moreover, they appear to hyperventilate slightly under basal conditions. The tests for peripheral chemoreceptor activity indicated no differences between the SUNCT and the control groups except for one variable, namely the mean ventilatory response to a single breath of 13% CO2. It is possible that this indicates a blunted response of the peripheral chemoreceptors. On the other hand, it may also represent a chance finding, since none of the other results presented suggested such a conclusion, and the size of the test group was very small. The results do not indicate that a reduction in oxygen saturation can trigger SUNCT since low levels of oxygen saturation were only rarely accompanied by SUNCT, whereas many attacks were not associated with any appreciable lowering in arterial oxygen saturation.

Aged↗
PubMed1995

Cigarette smoking and protection from Parkinson's disease: false association or etiologic clue?

We reviewed 46 published reports associating cigarette smoking and Parkinson's disease. Although the majority indicated an approximate halving of smoking frequency in persons with Parkinson's disease, many observers have suggested that the effect could be a spurious result. That the association may be real is suggested by at least six observations: (1) the consistency of findings between independent studies of different design, conducted by different investigators, in different nations, over 35 years; (2) the association's predominance and strength in prospective studies; (3) the apparent detection of a dose-response relation; (4) the inability to explain the association by confounding variables; (5) the flaws in certain arguments against the association's validity; and (6) the identification of a similar association, of similar magnitude, between smoking and reduced occurrence of Alzheimer's disease. A protective association of cigarette smoking for Parkinson's disease may constitute an important etiologic clue.

Female↗
PubMed1994

[Peptide modulation in vascular headache].

This article reviews recent developments in the field of vasoactive peptides in relation to certain types of headache. The equilibrium existing in the brain between contraction and dilatation of blood vessels is controlled by, among other factors, vasoactive peptides. Several of these have been discovered only recently and constitute a rapidly expanding field of research with exciting perspectives. Cranial blood vessels are innervated by sympathetic, parasympathetic and sensory nerve fibres, all of which contain certain vasoactive peptides as co-transmitters. Others, like endothelin, can be produced by the endothelium. There is evidence to suggest that vasoactive peptides of the trigeminovascular system are liberated in response to abnormal constriction of cranial blood vessels and contribute to headache. New drug therapies based on the activity of such substances are now being developed.

Cerebral Arteries↗
PubMed1994

Assessing cognitive abilities and dementia in a predominantly illiterate population of older individuals in Kinmen.

A community survey of dementia was conducted on a Chinese islet. A total of 221 men and 234 women in the age range of 50-92 were assessed. The Cognitive Abilities Screening Instrument (CASI), a 100-point cognitive test designed for cross-cultural studies and adapted in Chinese for individuals with little or no formal education, was administered twice by trained field workers with a retest interval of 3 to 4 weeks. In addition, all participants were assessed by physicians who did not know the CASI scores. The physicians' assessment included a complete neurological examination, plus semi-structured tests and interviews covering cognitive abilities, daily activities, depression, cerebrovascular disease, and Parkinson's disease. Dementia was diagnosed by consensus among the physicians according to the DSM-III-R criteria. Among the 455 participants, 16 cases of dementia were identified, including 13 with probable Alzheimer's disease and 1 each with vascular dementia, Parkinson's disease, and alcoholism. The rates of dementia were 0, 3.9 and 11.5% for the age groups of 50-69, 70-79 and 80-92; and 4.4, 2.0 and 0% for the education groups of 0-1, 2-6 and 7-15 years of schooling. No sex difference was found after controlling for education. The Chinese version of the CASI had an intraclass retest reliability of 0.90. Using a cut-off score of < or = 50 for dementia, the sensitivity was 0.88 and the specificity was 0.94. The preliminary study suggests that the CASI can be used in Chinese populations with generally low education levels and that Alzheimer's disease was the most common type of dementia in this population.

Aged↗
PubMed1994

Opportunities and challenges in international collaborative epidemiologic research of dementia and its subtypes: studies between Japan and the U.S.

Estimates of the prevalence rates for dementia vary significantly among countries. Such variation may be explained, at least in part, by methodologic differences in studies. The disparities in prevalence rates of dementia subtypes, particularly Alzheimer's disease and multi-infarct dementia, are especially apparent in studies conducted in Eastern and Western countries. In Japan and China, the prevalence of multi-infarct dementia exceeds that of Alzheimer's disease, whereas in the West, Alzheimer's disease predominates in the vast majority of studies. Clearly, cross-cultural studies of incidence using standard methods are needed to investigate whether a true difference in risk exists, and which risk factors differentially contribute to this variation. Migrant studies of genetically homogeneous populations offer a unique opportunity to answer these questions. This article explores the value of migrant studies, their application to etiologic questions of dementia and its subtypes, and recommendations concerning how to conduct such studies.

Aged↗
PubMed1994

Cluster headache: the peripheral chemosensitivity as indicated by the single-breath CO2 test.

A single-breath CO2 test was carried out in cluster headache patients both during bout and remission, and in matched healthy individuals (n = 10 for each group) to assess peripheral chemosensitivity. The test subjects inhaled one tidal breath of 13% CO2 in air. The response was expressed as the maximal increase in inspiratory minute ventilation (Vi) within 20 seconds from the exposure to CO2, divided by the increase in end-tidal PCO2 (PETCO2) (the difference in PCO2 between the test breath and the preceding control breaths): delta Vi/delta PETCO2. Under the initial resting condition, cluster headache patients within the bout showed a slight hyperventilation in that there was a significantly reduced PETCO2 (P < 0.05, Student's paired t-test), and during remission, higher Vi, and a lower PETCO2 (P < 0.05, Wilcoxon signed rank test), in comparison with the controls. There was no statistically significant difference as regards the peripheral chemosensitivity between cluster headache and control groups. These results indicate that cluster headache patients have an intact and properly-functioning carotid body.

Administration, Inhalation↗