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Biomedical subjects

C Lau

Publications and source records attributed to C Lau.

At least 127 records · Page 7Linked to original sources

Cognitive and neurologic findings in subjects with diffuse white matter lucencies on computed tomographic scan (leuko-araiosis).

As part of a prospective clinicopathologic study, a cohort of 105 "normal" elderly volunteers was investigated with computed tomographic scans, psychometric testing (Extended Scale for Dementia [ESD]) and neurologic examination. Computed tomographic scans were evaluated for the presence or absence of white matter lucencies, termed leuko-araiosis. These are defined as patchy or diffuse areas of decreased attenuation involving only white matter and with no change in adjacent ventricles or sulci. The nine controls with leuko-araiosis had lower scores on the ESD than the 96 controls without leuko-araiosis (mean ESD with leuko-araiosis, 227.1 +/- 14; without leuko-araiosis, 237.1 +/- 8), and the difference remains significant even after adjusting for the possible confounding effects of age, sex, education, and infarct detected on computed tomography. Significant differences were also found comparing subjects with leuko-araiosis and those without in respect to abnormal gait, limb power, plantar response, and the rooting and palmomental reflexes. Leuko-araiosis may represent a marker for early dementia. The pathophysiology of this finding remains uncertain. Our results suggest that white matter abnormalities play a role in the development of intellectual impairment in the elderly.

Aged↗

Cognitive and neurologic findings in demented patients with diffuse white matter lucencies on computed tomographic scan (leuko-araiosis).

A series of patients referred to the University of Western Ontario, London, Dementia Study for investigation of possible dementia underwent computed tomographic scans, psychometric testing (Extended Scale for Dementia [ESD]), and neurologic examination. Thirty-nine of the 113 patients studied (ischemic score, less than or equal to 4) were found to have leuko-araiosis, which we have defined as patchy or diffuse lucencies in the white matter. Patients with leuko-araiosis had significantly lower mean scores on the ESD, 109.7 +/- 61.2, compared with mean scores of 148.5 +/- 78.0 in those without. However, only a trend toward lower scores on the ESD was observed when age, sex, education, and infarct were taken into account in the analysis of covariance. Leuko-araiosis was found to be associated with increasing age, hypertension, abnormalities of power in the limbs, and extensor-plantar responses in this sample of patients. In patients with Alzheimer's disease (AD) alone, diagnosed clinically, 29 out of 91 demonstrated leuko-araiosis on computed tomography, but scores on the ESD in this group overall were not significantly different when those with and without leuko-araiosis were compared. In less advanced cases, however, a highly significant trend was evident for leuko-araiosis to be associated with increased dementia in AD. The results are consistent with the hypothesis that leuko-araiosis is associated with dementia in AD, and that this is either most marked or most easily identifiable before the dementia becomes very severe.

Aged↗

Vascular risk factors and leuko-araiosis.

Leuko-araiosis was found in 49 of 140 demented patients compared with 12 out of 110 control subjects. Thirty-one of 95 patients with dementia of the Alzheimer's type had leuko-araiosis. A history of stroke was four times more frequent in patients with leuko-araiosis than in those without leuko-araiosis (17.4% and 4.4%, respectively). It occurred in 25% of controls with leuko-araiosis compared with only 2% of those without leuko-araiosis. Mean systolic blood pressure was associated with leuko-araiosis. No association was found for diastolic blood pressure, myocardial infarction, angina, diabetes, or carotid bruits. On logistic regression analysis, the strong association between dementia and leuko-araiosis was mainly explained by a history of stroke. There are common factors in leuko-araiosis and stroke, but stroke alone does not account for leuko-araiosis.

Aged↗

The electroencephalogram in Alzheimer-type dementia. A sequential study correlating the electroencephalogram with psychometric and quantitative pathologic data.

As part of a longitudinal cohort study of dementia, 139 patients with Alzheimer's disease (dementia of the Alzheimer type, senile dementia of the Alzheimer type, and mixed type [ischemic score, 4 to 7]) and 148 age-matched control subjects were evaluated for electroencephalographic (EEG) abnormalities and their evolution. Electroencephalograms were significantly different in the two groups; EEGs worsened overall in the two groups during a period of one to four years, but most subjects showed no alteration in their EEGs. Some patients showed improvement in their EEG findings during the follow-up period. A strong correlation between EEG grade and psychometric scores was consistently found over sequential studies. In a subgroup of patients on whom autopsies were performed, morphometric neuron loss correlated significantly with EEG severity.

Aged↗

Regulation of adrenal chromaffin cell development by the central monoaminergic system: differential control of norepinephrine and epinephrine levels and secretory responses.

In the mature rat, reflex sympathetic stimulation by insulin-induced hypoglycemia resulted in profound depletion of adrenal epinephrine, and to a lesser extent, norepinephrine. In the developing rat, insulin evoked little or no secretory response from the adrenals prior to 1 week of age. By 7 days, a moderate depletion of epinephrine was seen and the magnitude of the response increased with age. In contrast, during the first 3 weeks of postnatal life, insulin failed to deplete norepinephrine from the adrenal medulla and in fact, produced an increase. This chiefly resulted from de novo biosynthesis of the amine, as the rise was blocked by alpha-methyl-p-tyrosine. These results suggest that the ontogeny of the two chromaffin cell types (norepinephrine and epinephrine-containing) in the adrenals and the maturation of their secretory responses are under differential regulation. Because descending supraspinal catecholaminergic and serotonergic systems have been implicated to play key roles in regulating adrenomedullary function, the ontogeny of the sympatho-adrenomedullary axis was evaluated after neonatal central lesioning with 6-hydroxydopamine or 5,7-dihydroxytryptamine. 6-Hydroxydopamine resulted in a preferential elevation of epinephrine in the developing adrenals as well as an increase in the responsiveness of the adrenals to reflex stimulation by insulin; the mature secretory pattern was obtained as early as at 4 days postnatally for epinephrine and 9 days for norepinephrine. In contrast, 5,7-dihydroxytryptamine led to a preferential reduction of basal adrenal norepinephrine content.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗

Platelet glycoprotein IIb. Chromosomal localization and tissue expression.

The GPIIb-IIIa complex functions as a receptor for cytoadhesive proteins on the platelet surface. Both GPIIb and GPIIIa are synthesized by a human erythroleukemia (HEL) cell line. We isolated several cDNA clones by screening a HEL cell cDNA library with an oligonucleotide derived from amino acid sequence of GPIIb. Nucleotide and amino acid sequences were determined from 703 bp of one of these clones. Amino acid sequence of purified platelet GPIIb peptides confirmed the identity of the clone. The cDNA encodes the carboxyl terminus of the large (alpha) subunit of GPIIb and all of the smaller (beta) subunit of GPIIb. By hybridizing the cDNA directly to chromosomes separated by dual laser chromosome sorting, the gene for GPIIb was mapped to chromosome 17. Northern blot analysis showed a approximately 3.4-kb GPIIb mRNA in HEL cells. We also compared the amino acid sequences determined from eight additional platelet GPIIb peptides with the derived amino acids from a published HEL cell GPIIb cDNA, and the platelet and HEL cell proteins appear to be the same. Despite previous reports that vascular endothelial cells and monocytes contain GPIIb, no GPIIb mRNA was observed in either type of cell. Thus, GPIIb appears to be specific for the platelet-megakaryocyte membrane and is distinct from the alpha subunits of the adhesion receptors in other normal tissues.

Amino Acid Sequence↗

Mammary resistance: a possible controlling factor in milk ejection.

At 8 and 13 days post partum, rats have the same total milk availability; yet, in response to suckling they release a greater amount of milk on day 13 than on day 8. Increased sensitivity to suckling in the more advanced lactators may result from a greater release of oxytocin or from changes in the mammary glands as lactation advances. The present study explores this latter possibility in anaesthetized dams at 8-9 and 13-15 days of lactation. Milk release and intramammary pressure were measured in anaesthetized dams in response to various doses of oxytoxin. Milk release was determined from the body weight gain of pups which had been fasted for 5 h before suckling on dams which had been isolated for 5 h. This parameter was significantly greater in 13- to 15-day lactators than in 8- to 9-day lactators over the range of oxytocin doses examined. In contrast, intramammary peak pressure and its dissipation time were significantly larger in the 8- to 9-day lactators than in the 13- to 15-day lactators. The compliance of the mammary glands was indirectly assessed at the two stages of lactation. When a constant pressure pulse was introduced into a cannulated gland, the resulting pressure peak was significantly greater in 8-day than in 13-day lactators, indicating a greater resistance in the former. Taken together, these results indicate that when endogenous oxytocin is inhibited (by anaesthesia) the greater milk release observed at the later stage of lactation in response to various doses of oxytocin may be due to a decline in mammary resistance as lactation progresses.

Animals↗

Origin of defective T lymphocyte-suppressor activating factor interaction in patients with rheumatoid arthritis.

We previously examined the generation of T cell released suppressor activity (TRSA) from peripheral blood T cells from patients with rheumatoid arthritis (RA) in response to a soluble suppressor activating factor (SAF) produced by a 6-thioguanine resistant mutant of the human T cell line CEM. We reported (Lau et al., 1985 Clin. exp. Immunol. 61, 481) that T cells from a substantial proportion of RA patients exhibited impaired TRSA release. To delineate further the TRSA abnormality observed in patients with active RA, we evaluated the kinetics of SAF activation, precursor frequency of SAF reactive cells and quantity of activated SAF released on a per cell basis. The results showed that a lower precursor frequency of SAF reactive cells accounted for defective TRSA release in a majority of RA patients, while TRSA release on a per cell basis was normal. The defective TRSA response to SAF could not be explained by abnormal dose kinetics of SAF, time kinetics of TRSA release or prior in vivo lymphocyte activation of the RA T cells.

Adult↗

Electrocardiographic findings in 204 residents of homes for the aged.

Electrocardiograms from 204 subjects aged 60 and above, residing in homes for the aged, were analysed. 13% had evidence of cardiovascular disease. 55% of the electrocardiograms showed at least one abnormality. At least 10% of electrocardiograms showed left atrial hypertrophy, first degree atrioventricular block, right bundle branch block, pathologic Q waves, ST-T abnormalities, or prolonged QT interval. Findings predictive of cardiovascular disease were left ventricular hypertrophy patterns and ST-T abnormalities, or prolonged QT interval. Findings predictive of cardiovascular disease were left ventricular hypertrophy patterns and ST-T abnormalities. Increase of age from 60 to 100 years was associated with prolongation of PR and QT intervals, but shortening of the RR interval.

Aged↗

Effects of prenatal nitrofen exposure on cardiac structure and function in the rat.

The herbicide nitrofen was administered to pregnant Fischer-344 and Sprague-Dawley rats on Days 10-13 of gestation (po, 20 or 40 mg/kg daily) and its effects on cardiac structure and function were investigated in the offspring. In the 21-day fetuses, nitrofen did not influence intrauterine growth or basal heart rate. In contrast, the herbicide produced a marked depression of heart rate and abnormal electrocardiographic (ECG) profiles in the newborn rats, in conjunction with labored respiratory movements and a profound increase in postnatal mortality. A few animals displayed cardiac ventricular septal defects and diaphragmatic hernias but these malformations did not appear to be associated with the ECG changes. The chronotropic deficiencies seen in the nitrofen-treated pups were reversible by acute hyperoxia (40% oxygen). These results suggest that the teratogenic effects of nitrofen on cardiac physiology and on postnatal mortality cannot be accounted for solely by specific gross anatomical damages to the rat heart and diaphragm; rather, other more subtle morphological and physiological factors which contribute to improper systemic delivery and cellular utilization of oxygen may be involved.

Animals↗

Investigation of the nature of the "stretch response" in suckling rats.

The "stretch response" in suckling rats has commonly been used as an index of milk ejection and milk intake. In the current study, we have compared the behavior of pups suckling on dams with either full, empty or ligated mammary glands. In response to an IV bolus of oxytocin, pups suckling on both full and empty nipples displayed the characteristic stretch behavior. Lack of milk release from the latter nipples was confirmed by lack of weight gain by the pups. In contrast to pups suckling on intact nipples, those suckling on ligated nipples did not display the stretch response. It is concluded that this behavior occurs in response to erection of the nipple and is not necessarily associated with milk release.

Animal Population Groups↗

Development of serotonergic and adrenergic receptors in the rat spinal cord: effects of neonatal chemical lesions and hyperthyroidism.

The sympathetic preganglionic neurons in the spinal cord receive dense serotonergic (5-HT) and catecholaminergic (CA) afferent inputs from the descending supraspinal pathways. In the rat spinal cord, the levels of these biogenic amines and their receptors are low at birth, but undergo rapid ontogenetic increases in the ensuing 2-3 postnatal weeks until the adult levels are reached. In many systems it has been shown that denervation of presynaptic neurons leads to an up-regulation of the number of postsynaptic receptors. To determine whether the 5-HT and CA receptors in the developing spinal cord are also subject to such transsynaptic regulation, we examined the ontogeny of serotonergic receptors and alpha- and beta-adrenergic receptors in thoracolumbar spinal cord of rats given neurotoxins which destroy serotonergic (5,7-dihydroxytryptamine (5,7-DHT)) or noradrenergic (6-hydroxydopamine (6-OHDA)) nerve terminals. Intracisternal administration of 5,7-DHT or 6-OHDA at 1 and 6 days of age prevented, respectively, the development of 5-HT and CA levels in the spinal cord. Rats lesioned with 5,7-DHT displayed a marked elevation of 5-HT receptors with a binding of 50% greater than controls at 1 week and a continuing increase to twice normal by 4 weeks. A similar pattern of up-regulation was also detected with the alpha-adrenergic receptor, as rats lesioned with 6-OHDA exhibited persistent increases in receptor concentration. However, in these same animals ontogeny of the beta-adrenergic receptor in the spinal cord remained virtually unaffected by the chemical lesion. In several other parts of the nervous system, it has been demonstrated that the beta-adrenergic sensitivity can be modulated by hormonal signals, particularly that of the thyroid hormones. This phenomenon was examined in the spinal cord and in confirmation with previous studies neonatal treatment of triiodothyronine (0.1 mg/kg, s.c. daily) was capable of evoking persistent increases in beta-adrenergic receptor binding. These results suggest that: (a) development of the postjunctional serotonergic and alpha-adrenergic receptors in the rat spinal cord can occur in the absence of the prejunctional nerve terminals and are subject to transsynaptic modulation; (b) beta-adrenergic receptors in the spinal cord also can develop after prejunctional lesions but are regulated by hormonal rather than neuronal factors.

Animals↗

Impaired release of a T-cell specific suppressor factor in rheumatoid arthritis.

Peripheral blood T cells from patients with rheumatoid arthritis (RA) and scleroderma (PSS) were assessed for their ability to release T-cell-specific suppressor activity (TRSA) upon incubation with a suppressor activating factor (SAF) derived from a human lymphoblastoid cell line (CEM). T cells from 11/20 (55%) RA patients exhibited impaired TRSA release in contrast to 1/12 (8%) of PSS patients. RA patients demonstrating impaired TRSA release exhibited more active arthritis than patients demonstrating normal TRSA release.

Adult↗

Regulation of milk ingestion in the infant rat.

The aim of this study was to differentiate between maternal and offspring factors involved in the control of milk ingestion. Specifically, we investigated: (1) the temporal pattern of milk ingestion in fasted and non-fasted sucklings; (2) the amount of milk released as compared to that of milk available; and (3) the roles of the age of pups and the lactational stage of the dam as determinants of milk release. There were three general findings. First, the temporal pattern of milk letdown following a 5-hr accumulation consisted of an initial rapid phase followed by a slow "maintenance" phase. Second, a limiting factor in the amount of milk released is the dam's sensitivity to the suckling stimulus which changes as lactation progresses. Third, the age of the pups does not appear to play a determining role in milk release, but the degree of their deprivation does. In summary, it is suggested that compensation for weight loss during a fast in infant rats depends on an interplay between the pups' ability to increase their own intake, the milk availability, and the maternal sensitivity to suckling.

Age Factors↗

Conditions influencing formation of 16:0/16:0 molecular species in membrane phospholipids of Escherichia coli.

Growth of a beta-oxidation-negative (fadE) strain of Escherichia coli in liquid culture with exogenous palmitate leads to the accumulation of 16:0/16:0 molecular species of phospholipid resulting in a temporary decrease in growth rate and lysis of a variable fraction of the cell population. Under the same growth conditions, this behavior is not seen in the closely related fadE+ parent strain which accumulates more modest levels of 16:0/16:0 together with 16:0/14:0. Based on differential scanning calorimetric measurements, 75.8 and 17.5% of the lipids from 16:0-enriched fadE and fadE+ cells, respectively, were found to be in the gel state at the growth temperature. Kinetic studies reveal the translocation of 16:0/16:0 molecular species from inner to outer membrane delays briefly the accumulation of this species in the inner membrane. This extreme and deleterious change in membrane-lipid composition precludes cloning of the fadE strain on solid media containing 16:0 and, therefore, these conditions provide the basis for selection of mutants altered in the mechanisms which determine the synthesis or accumulation of membrane lipid. Three such mutants are described which display alterations in the normal distribution of molecular species.

Calorimetry, Differential Scanning↗