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L R White

Publications and source records attributed to L R White.

At least 55 records · Page 3Linked to original sources
PubMed1998

[U-13C] aspartate metabolism in cultured cortical astrocytes and cerebellar granule neurons studied by NMR spectroscopy.

The metabolism of [U-13C]aspartate was studied in cultured cortical astrocytes and cerebellar granule neurons in the presence of glucose and during inhibition of glycolysis. Redissolved, lyophilized cell extracts and incubation media were analyzed by 13C nuclear magnetic resonance spectroscopy for the determination of metabolites labeled from aspartate. Uniformly labeled lactate was prominent in control media of astrocytes and cerebellar granule neurons. In both cell types, aspartate entered the tricarboxylic acid (TCA) cycle, as shown by labeling patterns in glutamate and, in astrocytes, in glutamine. From the complex labeling patterns in aspartate in astrocytic perchloric acid extracts it was clear that acetylcoenzyme A (acetyl-CoA) derived from aspartate via oxaloacetate and pyruvate could enter the TCA cycle. Such "recycling," however, could not be detected in cerebellar granule neurons. Inhibition of glycolysis reduced aspartate uptake and metabolism in both cell types. Most notably, lactate derived from aspartate showed a large reduction, and in astrocytes, incorporation of labeled acetyl-CoA into the TCA cycle was significantly reduced. Thus, astrocytes and cerebellar granule neurons differ in their handling of aspartate. Furthermore, inhibition of glycolysis clearly affected aspartate metabolism by such cells.

Acetyl Coenzyme A↗
PubMed1998

Increased endothelin ETB contractile activity in cultured segments of human temporal artery.

Contractions induced by endothelin-1, endothelin-3 and the selective ETB agonist, sarafotoxin S6c, were studied in segments of human temporal artery. The results in fresh arteries were compared with those obtained after 1 or 4 days in organ culture, and with the specific ETA antagonist FR 139,317, the specific, mixed antagonist bosentan, or the specific ETB antagonist, BQ 788. Sarafotoxin S6c induced no contractile activity in fresh artery segments, but elicited marked contractions after culture. This contraction was only slightly inhibited by FR 139,317, but was abolished by BQ 788. Contractions induced by endothelin-1 were antagonized by FR 139,317 and bosentan, but not by BQ 788. Organ culture did not change the overall pattern, but all concentration-response curves were shifted leftwards. Contractions induced by endothelin-3 were abolished by all antagonists in fresh arteries, but some activity was restored after organ culture. Sensitivity to endothelin-3 was markedly increased. The results suggest a change in endothelin receptors during organ culture, resulting in a marked increase in contractile ETB activity, and possibly some increase in ETA activity. Such changes illustrate the complexity of endothelin responses in this vascular bed.

Azepines↗
PubMed1998

Phonophobia in migraine.

Quantitative measurement of sound-induced discomfort and pain thresholds showed that migraineurs (n = 65) were significantly more sensitive than headache-free controls (n = 80), both during and outside attack (p < 0.0001). Patients tested with head pain had lower thresholds than those tested without pain (p < 0.01). Migraine with and without aura did not differ as to sound sensitivity. There were no significant differences in thresholds between the symptomatic and nonsymptomatic sides (p > or = 0.78). Patients with unilateral headache or pain of pulsating character were more sensitive than those with bilateral headache or pressing pain (p < 0.05). Phonophobia did not correlate significantly with duration, frequency, or severity of attacks. The main results were in accordance with a questionnaire study concerning subjective evaluation of sound sensitivity. Similarities between phonophobia and photophobia in migraine provide evidence that both phenomena share a common pathophysiological mechanism in this condition.

Adult↗
PubMed1998

In vitro and ex vivo 13C-NMR spectroscopy studies of pyruvate recycling in brain.

Pyruvate recycling is a well established pathway in the liver, but in the brain, the cellular localization of pyruvate recycling remains controversial and its physiological significance is unknown. In cultured cortical astrocytes, pyruvate formed from [U-13C]glutamate was shown to re-enter the TCA cycle after conversion to acetyl-CoA, as demonstrated by the labelling patterns in aspartate C-2 and C-3, lactate C-2, and glutamate C-4, which provides evidence for pyruvate recycling in astrocytes. This finding is in agreement with previous studies of astrocytic cultures, in which pyruvate recycling has been described from [U-13C]glutamine, in the presence of glutamate, and from [U-13C]aspartate. Pyruvate recycling in brain was studied in fasted rats receiving either an intraperitoneal or a subcutaneous injection of [1,2-13C]acetate followed by decapitation 30 min later. Extracts of cortical tissue were analysed with 13C-NMR spectroscopy and total amounts of amino acids quantified by HPLC. Plasma extracts were analysed with 1H- and 13C-NMR spectroscopy, and showed a significantly larger amount of [1, 2-13C]acetate in the intraperitoneal group compared to the subcutaneous group. Furthermore, a small amount of label was detected in glucose in both groups. In the subcutaneously injected rats, [4-13C]glutamate and [2-13C]GABA were less enriched than plasma glucose, which might have been the precursor. In the intraperitoneally injected rats, however, pyruvate formation from [1, 2-13C]acetate, and re-entry of this pyruvate into the TCA cycle was demonstrated by the presence of greater 13C enrichment in [4-13C]glutamate and [4-13C]glutamine compared to the subcutaneous group, probably resulting from the significantly higher [1, 2-13C]acetate concentration in brain and plasma.

Acetates↗
PubMed1998

Height as a marker of childhood development and late-life cognitive function: the Honolulu-Asia Aging Study.

OBJECTIVE: Growing evidence suggests that structural and functional brain reserves, thought to develop in childhood and adolescence, may be crucial in determining when cognitive impairment begins. The purpose of this report is to examine the relationship of height, as a marker of childhood development, to late-life cognitive function in a sample of elderly Japanese-American men. METHOD: Cognitive performance was assessed from 1991 to 1993 in the Honolulu-Asia Aging Study in 3733 men aged 71 to 93 years and related to height that was measured 25 years earlier. RESULTS: Among the study sample, shorter men were older, leaner, and less educated than taller men. Shorter men also spent more years of their childhood living in Japan and were more likely to have had fathers in unskilled professions. After adjustment for age, the prevalence of poor cognitive performance declined consistently with increasing height from 25% in men shorter than 154 cm (61 in) to 9% in those taller than 174 cm (69 in). Excluding men with stroke or dementia did not alter the association between height and cognitive performance. Apolipoprotein E4 was unrelated to height and did not effect the association between height and cognitive function. The prevalence of Alzheimer's disease was higher in men who were 154 cm (61 in) or shorter as compared with men who were taller (4.7% vs 2.9%, respectively). There was no association between height and vascular dementia. CONCLUSION: Efforts to improve prenatal and early life conditions to maximize growth in childhood and adolescence could diminish or delay the expression of cognitive impairments that occur later in life. Prevention of some late-life cognitive impairments may have pediatric origins.

Aged↗
PubMed1998

Predictors of healthy aging in men with high life expectancies.

OBJECTIVE: The purpose of this study was to identify risk factors that consistently predict staying healthy in contrast to developing clinical illness and/or physical and mental impairments. METHODS: More than 8000 men of Japanese ancestry were followed for 28 years with repeat examinations and surveillance for deaths and incident clinical illness. Physical and cognitive functions were measured in 1993. Measures of healthy aging included surviving and remaining free of major chronic illnesses and physical and cognitive impairments. RESULTS: Of 6505 healthy men at baseline, 2524 (39%) died prior to the final exam. Of the 3263 available survivors, 41% remained free of major clinical illnesses, 40% remained free of both physical and cognitive impairment, and 19% remained free of both illness and impairment. The most consistent predictors of healthy aging were low blood pressure, low serum glucose, not smoking cigarettes, and not being obese. CONCLUSIONS: Beyond the biological effects of aging, much of the illness and disability in the elderly is related to risk factors present at midlife.

Aged↗
PubMed1997

Lactate formation from [U-13C]aspartate in cultured astrocytes: compartmentation of pyruvate metabolism.

Metabolism of [U-13C]aspartate in cultured astrocytes and the effects of inhibitors of malic enzyme and phosphoenolpyruvate carboxykinase (hydroxymalonate and 3-mercaptopicolinic acid, respectively) were studied using 13C nuclear magnetic resonance (NMR) spectroscopy. The labelling of glutamate and glutamine showed entry of aspartate into the tricarboxylic acid (TCA) cycle after conversion to oxaloacetate. Production of [U-13C]pyruvate from [U-13C]aspartate was revealed by the presence of [U-13C]lactate in incubation media. Furthermore, labelling patterns in C-2 and C-3 in intracellular aspartate showed entry of [1,2-13C]acetyl-CoA into the TCA cycle; evidence for pyruvate-recycling. No reduction in [U-13C]lactate was observed in the presence of either enzyme inhibitor. However, 3-mercaptopicolinic acid reduced incorporation of labelled acetyl-CoA into TCA cycle intermediates, indicating compartmentation of pyruvate production in astrocytes.

Animals↗
PubMed1997

Nuclear magnetic resonance spectroscopy of cerebrospinal fluid from patients with low back pain and sciatica.

STUDY DESIGN: This study was carried out to assess the metabolic differences between pain-free control subjects and patients with low back pain, either with or without disc protrusion or herniation. OBJECTIVES: To analyze various metabolites in human cerebrospinal fluid using proton nuclear magnetic resonance spectroscopy. The potential use of this technique as an additional tool for diagnostic assessment was also evaluated. SUMMARY OF BACKGROUND DATA: Inflammation is thought to play a major role in the generation of lumbar spine pain, a theory supported both by animal and in vitro studies. The effect of the inflammation in terms of increased metabolism has not yet been studied. METHODS: Cerebrospinal fluid was obtained from patients by lumbar puncture, frozen, redissolved, and analyzed for metabolites by proton nuclear magnetic resonance spectroscopy. RESULTS: Significantly lower values for several key metabolites were found in patients with low back pain or sciatica, with the lowest values in the subgroup of patients with myelographic signs of disc protrusion or herniation. CONCLUSIONS: The results indicate a higher level of metabolic activity in patients with low back pain or sciatica compared with pain-free control subjects, with this difference being most pronounced in the subgroup of patients with myelographic evidence of disc protrusion or herniation.

Adult↗
PubMed1997

Smoking history in middle age and subsequent cognitive performance in elderly Japanese-American men. The Honolulu-Asia Aging Study.

The associations between cigarette smoking history and later cognitive performance were examined among 3,429 Japanese-American participants of the Honolulu Heart Program (HHP) and its extension, the Honolulu-Asia Aging Study (HAAS). Cognitive performance was measured by the Cognitive Abilities Screening Instrument (CASI), administered as part of HAAS (mean age at HAAS exam (standard deviation (SD)): 77.7 (4.6) years). Information on smoking history was collected during the first and third HHP exams (mean age (SD) at Exam III: 58.6 (4.7) years). Compared with never-smokers, those who had smoked continuously between Exams I-III and those who had quit smoking during that period had significantly lower CASI scores, after adjustment for age, education, Japanese acculturation, and Exam III alcohol intake. In multiple logistic regression controlling for the above covariates, a significantly higher risk of cognitive impairment (CASI score < 82) was associated with continuous smoking (odds ratio (OR) = 1.36, 95% confidence interval (CI) 1.10-1.69) and quitting between Exams I-III (OR = 1.36, 95% CI 1.03-1.80) compared with never smoking. This excess risk of cognitive impairment among continuous smokers and Exam I-III quitters was slightly diminished by further adjustment for body mass index and several vascular covariates. Additional analyses suggested a reduced risk of cognitive impairment among the longer-term quitters. This study suggests a positive association between smoking during middle age and later risk of cognitive impairment.

Aged↗
PubMed1997

NMR spectroscopy study of the effect of 3-nitropropionic acid on glutamate metabolism in cultured astrocytes.

3-Nitropropionic acid (3-NPA) is a selective and irreversible inhibitor of succinate dehydrogenase. The effect of this compound on the metabolism of [U-13C]glutamate was studied in astrocytes using 13C nuclear magnetic resonance spectroscopy. The appearance of [1,2,3-13C]glutamate in cell extracts and [1,2,3-13C]glutamine and [U-13C]lactate in cell media demonstrated the metabolism of labeled glutamate via the tricarboxylic acid cycle. Such labeling was observed in the control situation and also in cells treated with 3 mM 3-NPA. In the cells treated with 3 mM 3-NPA, however, the labeling was significantly reduced, and with 10 mM 3-NPA no such labeling was observed. Labeled aspartate was observed in untreated cells only. Labeled succinate was not detectable under control conditions, but increased dose dependently in the presence of 3-NPA. Glutamate uptake and conversion of [U-13C]glutamate to [U-13C]glutamine was largely unaffected by 3-NPA, and ATP content was unchanged. In a previous study using cerebellar neurons, tricarboxylic acid cycle metabolism was blocked with 3 mM 3-NPA. The present results show that astrocyte metabolism is more adaptable to blockade of the tricarboxylic acid cycle by 3-NPA than neuronal metabolism.

Animals↗
PubMed1997

Frequency and characteristics of silent dementia among elderly Japanese-American men. The Honolulu-Asia Aging Study.

OBJECTIVE: To determine the frequency of unrecognized dementia in a group of men found to have dementia by population survey, and to identify factors associated with the failure of a family informant to recognize significant memory impairment. DESIGN AND SETTING: The Honolulu-Asia Aging Study, a population-based study of dementia among elderly Japanese-American men living on the island of Oahu, Hawaii. Data for this study were from the dementia prevalence survey, 1991-1993. STUDY PARTICIPANTS: A total of 191 noninstitutionalized men with dementia who had a reliable family informant. MAIN OUTCOME MEASURES: Failure of family informants to recognize a problem with thinking or memory in subjects with dementia. RESULTS: A total of 21% of family informants failed to recognize a problem with memory among subjects subsequently found to have dementia. Among subjects with very mild dementia, 52% of family informants failed to recognize a significant memory problem compared with 13% among more severely demented subjects. Of the subjects with dementia whose family informants did recognize a memory problem, 53% failed to receive a medical evaluation for this problem. For all family informants, increasing age, fewer years of education, less severe dementia, fewer behavioral complications, fewer functional disabilities, and better performance on certain tests of memory and language were significantly associated with the family informant's failure to recognize a problem with memory. When the family informants were wives living with husbands, less severe dementia, fewer behavioral complications, fewer functional disabilities, and intact remote memory were associated with unrecognized dementia. CONCLUSIONS: Unrecognized dementia was common in our population, especially among mild cases. Cognitive screening programs for the elderly and public education policies designed to increase awareness of early signs of dementia are needed if interventions for individuals with potentially treatable dementias are to be implemented.

Aged↗
PubMed1997

Light-induced discomfort and pain in migraine.

Quantitative thresholds for discomfort and pain with monocular and binocular light stimuli were measured in 67 controls and 67 migraine patients (37 migraine with aura and 30 migraine without aura). Patients were more photophobic during attack than outside attack (p < 0.03), and they were more sensitive to light than controls even between attacks (p < or = 0.0001). We found no differences in light sensitivity between migraine with aura and migraine without aura (p > or = 0.93). Unilateral pain affected light sensitivity on both sides. When asked with a questionnaire, 74% of patients answered that they were sensitive to light outside attack and 100% were sensitive during attack. Pain thresholds were generally lower among sensitive than non-sensitive patients (p = 0.004), indicating some agreement between subjective opinion and objective measurements of photophobia. Photophobia seems to be an intrinsic property of migraineurs. It is increased by migraine pain, but seems to be unrelated to migraine characteristics such as nausea, severity of attacks, pain character and pain laterality.

Adolescent↗
PubMed1997

Cerebrospinal fluid lactate and glutamine are reduced in multiple sclerosis.

OBJECTIVES: To analyse various metabolites in human cerebrospinal fluid from healthy controls and patients with multiple sclerosis. PATIENTS AND METHODS: Cerebrospinal fluid was obtained from patients by lumbar puncture, frozen, redissolved, and analysed for metabolites by proton nuclear magnetic resonance spectroscopy. RESULTS: Significantly lower values for lactate and glutamine were found in patients with multiple sclerosis in comparison with controls. No significant differences were found between patients with the relapsing-remitting and chronic progressive forms of the disease for any of the metabolites measured. CONCLUSION: There is a concomitant reduction in both lactate and glutamine in the cerebrospinal fluid of patients with multiple sclerosis compared to controls. This may be related to altered astrocytic metabolism during the disease. The results clearly show the diagnostic potential of magnetic resonance spectroscopy in diseases such as multiple sclerosis.

Adolescent↗
PubMed1997

Evidence for a possible synergism between pituitary adenylate cyclase activating polypeptide and calcitonin gene-related peptide in porcine ophthalmic artery.

The activities of pituitary adenylate cyclase activating polypeptide (PACAP) and calcitonin gene-related peptide (CGRP) were investigated in isolated segments of porcine ophthalmic artery. In artery segments pre-contracted by prostaglandin F2alpha, PACAP induced a concentration dependent relaxation, but was clearly less potent than CGRP. When 2 x 10(-10) M CGRP (relaxation 4.3 +/- 0.8%, n = 11) and 10(-8) M PACAP (relaxation 12.4 +/- 3.8%, n = 10) were added together, the subsequent relaxation was substantially increased (33.6 +/- 5.6%, p<0.0005). In addition, the rate of relaxation was increased. The results indicate that there is synergism between low concentrations of CGRP and PACAP in isolated porcine ophthalmic artery.

Animals↗
PubMed1997

Computerized analysis of isometric tension studies provides important additional information about vasomotor activity.

Concentration-response curves of isometric tension studies on isolated blood vessels are obtained traditionally. Although parameters such as Imax, EC50 and pA2 may be readily calculated, this method does not provide information on the temporal profile of the responses or the actual nature of the reaction curves. Computerized data acquisition systems can be used to obtain average data that represent a new source of otherwise inaccessible information, since early and late responses may be observed separately in detail.

Animals↗
PubMed1996

Observations on serum uric acid levels and the risk of idiopathic Parkinson's disease.

Uric acid, an antioxidant found in high concentrations in serum and in the brain, has been hypothesized to protect against oxidative damage and cell death in Parkinson's disease. The authors tested this hypothesis among men participating in a 30-year prospective study known as the Honolulu Heart Program. Serum uric acid was measured in 7,968 men at the baseline examination held from 1965 to 1968. Of these men, 92 subsequently developed idiopathic Parkinson's disease (IPD). In analyses adjusted for age and smoking, men with uric acid concentrations above the median at enrollment had a 40% reduction in IPD incidence (rate ratio (RR) = 0.6; 95% confidence interval (CI) 0.4-1.0). Reduced IPD incidence rates persisted in analyses restricted to nonsmokers (RR = 0.5; 95% CI 0.3-1.0) and cases younger than age 75 years (RR = 0.5; 95% CI 0.3-0.9). Incidence rates were not notably affected when analyses were restricted to cases that occurred more than 5 years after uric acid measurement (RR = 0.6; 95% CI 0.4-1.0). Inclusion of known or computed correlates of uric acid in regression models did not substantially change risk of IPD. This study provides prospective evidence of an association between uric acid and reduced occurrence of IPD and indicates that further investigations of this association are warranted.

Aged↗
PubMed1996

Evidence against the operation of selective mortality in explaining the association between cigarette smoking and reduced occurrence of idiopathic Parkinson disease.

To investigate the association between idiopathic Parkinson disease (IPD) and reduced frequency of prior cigarette smoking, the authors compared the 29-year follow-up mortality rates and IPD incidence rates of men who were either cigarette smokers or nonsmokers at the time of enrollment in the Honolulu Heart Study (1965-1968). Based on IPD cases detected up to June 30, 1994, the age-adjusted incidence rate in smokers was less than half that in nonsmokers: 34.4 versus 94.2 cases per 100,000 person-years of pre-illness follow-up, respectively. When data were stratified by 5-year age group, lower IPD incidence in smokers was observed at all ages between 50 and 90 years. Age-specific mortality trends for smokers and nonsmokers with and without IPD suggested that increased mortality in IPD patients was mostly associated with IPD itself and not with smoking. The slight excess mortality in smokers without IPD, versus nonsmokers without IPD, appeared insufficient to account for the "missing" incident IPD cases in smokers. These IPD incidence and mortality data are not highly consistent with the "selective mortality" hypothesis, which attributes reduced prior smoking frequency, typically reported by persons with IPD, to accelerated mortality in undiagnosed IPD-affected persons who smoke. The "protective" association of cigarette smoking with IPD occurrence may thus be real, suggesting the need for further study of biologic mechanisms of protection.

Age Distribution↗