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Biomedical subjects

C Lau

Publications and source records attributed to C Lau.

At least 109 records · Page 6Linked to original sources
PubMed1989

Prenatal alpha-difluoromethylornithine treatment: effects on postnatal renal growth and function in the rat.

DFMO (alpha-difluoromethylornithine) is a specific irreversible inhibitor of ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines, which in turn control macromolecule synthesis during cell proliferation. The current study was designed to investigate the effects of inhibition of ODC during discrete prenatal periods on renal growth and function. We administered 5 doses of 500 mg/kg DFMO or saline s.c. to timed pregnant Sprague-Dawley rats at 12 hr intervals beginning on gestation days (GD) 11, 14, or 17. Half the dams were killed on GD 20 for fetal morphological analyses and half were allowed to go to term. Renal function was assessed on postnatal days (PD) 3, 6, 10, and 14 by tests of basal renal clearance and urinary concentrating ability, and on PD 42-44 we measured serum chemistries. All three gestational treatment regimens resulted in postnatal deficits in general growth. Only in the GD 11-13 treatment group was there evidence of embryotoxicity and neonatal renal pathophysiology. Fetal weights and urogenital morphology were altered following GD 14-16 treatment and there were persistent deficits of renal growth. GD 17-19 treatment was associated only with transient postnatal deficits of renal growth. Thus, inhibition of ODC during critical prenatal periods induced distinct developmental effects. However, there were no associations between impaired renal growth and function. These data indicate that general tissue growth is not always a predictor of physiological development and support the necessity of multifaceted approaches to the understanding of adverse developmental effects.

Analysis of Variance↗
PubMed1989

Characterization of the mammalian toxicity of the crystal polypeptides of Bacillus thuringiensis subsp. israelensis.

Solubilized crystal polypeptide preparations of Bacillus thuringiensis subsp. israelensis (BTI) were fractionated by immunoaffinity chromatography using a bound monoclonal antibody formed against the 28K crystal polypeptide. The 28K polypeptide was confirmed to be hemolytic and to possess low mosquitocidal activity against Aedes aegypti larvae. By comparison, the 28K polypeptide was more potent than the solubilized BTI crystals in male Swiss Webster mice, as the LD50 values were (p less than 0.05) 0.77 and 2.33 mg protein/kg body wt, respectively. Acute administration of the 28K polypeptide (mg/kg, ip) produced severe hypothermia and bradycardia in the mouse. No evidence for cooperativity between the 28K and other crystal polypeptides was observed. Preliminary histological examination of the mouse hearts exposed to the 28K polypeptide did not reveal any specific lesion, suggesting that the deficient cardiac performance might be a secondary physiological response. Gross pathological examination of mice as well as Sprague-Dawley rats acutely treated with equivalent doses of solubilized BTI crystal preparations revealed focal to segmental reddened and edematous areas within the small intestine. Histopathology indicated that the major lesion was in the jejunum. Contrary to expectations from in vitro hemolysis assays, cytolysis of mouse red and white blood cells was not detectable after in vivo exposure to the BTI solubilized proteins. The present results indicate that the 28K polypeptide is the mammalian toxic component of BTI crystals.

Aedes↗
PubMed1989

A noninvasive method for determining patterns of milk intake in the breast-fed infant.

A noninvasive adaptation of the test-weighing method has been devised for continuously monitoring milk intake in breast-fed infants. This procedure consists of counting the number of swallows from videotaped sessions of individual feeds and correlating them to the corresponding pre- and postnursing weights of the infants. The method has been tested on four nursing sessions in twins aged 1 1/2 to 2 1/2 months. A high correlation was found between swallow counts and weight gain of the babies. The patterns of milk intake as monitored by these two parameters were similar. This method has the advantage of not disrupting the natural nursing process because test-weighing during the feeding session is not necessary. In addition, it allows for longitudinal studies and uses relatively simple equipment, i.e., a balance and a video camera. It is further suggested that monitoring swallowing in the manner described herein may be a valuable addition to studies on sucking behavior in human infants. Finally, it is noted from the data presented that the pattern of milk transfer in a mother breast-feeding twins is different from that observed in mothers breast-feeding singletons who were monitored by means of a cross-sectional test-weighing procedure.

Breast Feeding↗
PubMed1988

Thyroid hormone control of preganglionic innervation of the adrenal medulla and chromaffin cell development in the rat. An ultrastructural, morphometric and biochemical evaluation.

In the rat, functional connections between the splanchnic nerve and the adrenal medulla are immature at birth and do not become fully competent until the first postnatal week. Neonatal administration of triiodothyronine (T3) accelerates this process, and the present study was undertaken to elucidate the underlying mechanisms. Rats were given T3 (0.1 mg/kg, s.c.) daily for 9 days beginning 1 day after birth. Preganglionic innervation of the adrenal medulla was examined by retrograde axonal transport of horseradish peroxidase (HRP). At 10 days of age, there was an increased number of labeled perikarya in the spinal cord of the hyperthyroid pups. Ultrastructural examination revealed a corresponding increase in synaptic density in the adrenal medulla and in the activity of choline acetyltransferase, a marker for preganglionic cholinergic nerve terminals. These effects were attenuated by 25 days of age, whereupon deficits in HRP-labeled neurons and adrenomedullary synapses were noted. Similarly, replication of chromaffin cells was enhanced transiently in the T3 group during the initial stage of hyperthyroidism, but subsequent long-lasting deficits in cell numbers were noted, along with a corresponding retardation of ontogeny of adrenal catecholamine biosynthesis and storage. Thus, neonatal hyperthyroidism accelerates synaptic development in the sympatho-adrenal axis but suppresses maturation of the target chromaffin cells, ultimately leading to impaired adrenomedullary function.

Adrenal Medulla↗
PubMed1988

Teratogenic effects of nitrofen on cellular and functional maturation of the rat lung.

The herbicide nitrofen was administered to pregnant Sprague-Dawley and Fischer-344 rats on Days 10-13 of gestation (po, 20 or 40 mg/kg daily) and the effects of maturation of the perinatal lung were evaluated. Nitrofen interfered with the ontogenetic acquisition of lung cells as DNA, RNA, and protein content were subnormal. The hypoplastic lungs in the newborns were associated with structural deficits, resulting in a profound reduction of surface area available for gas exchange and depressed lung compliance. Other factors which influence pulmonary function and systemic delivery of oxygen were also considered. Adrenal catecholamines, which play an important role in surfactant production and fluid resorption in the lung during the transition to air-breathing, were markedly reduced. In addition, red blood cell concentration was significantly diminished. Taken together, these results suggest that the neonatal mortality observed in the nitrofen-treated rats is likely associated with respiratory distress caused by a number of cellular and functional aberrations. These include (a) hypoplasia and structural defects in the lung leading to deficient pulmonary function, (b) deficits in adrenal catecholamines potentially impeding the transition of the lung to air-breathing, and (c) impaired systemic delivery of oxygen due to reduced hemoglobin concentration.

Adrenal Medulla↗
PubMed1988

Sensitivity and specificity of the extended scale for dementia.

The Extended Scale for Dementia was introduced as a test for grading the intellectual function of patients with dementia. Its use in discriminating demented patients from nondemented control subjects has been explored. The test had a sensitivity of 93% and a specificity of 96% in patients over the age of 65 years, but the sensitivity fell to 75% in those younger than 65 years. The scale may be useful, particularly for patients over the age of 65 years, in helping to distinguish dementia from normality.

Aged↗
PubMed1988

A new method for the artificial raising of infant rats: the palate cannula.

Chronic removal of infant rats from their mother prior to the onset of weaning is complicated by the fact that young rats do not easily suckle from an artificial nipple. Thus, a method of artificial raising is advantageous for developmental investigations of nutrition or ingestive behaviors during the suckling period. The intragastric cannula has become a popular method for this purpose. However, for many studies, it would be advantageous if the diet could be administered to the mouth and actually swallowed by the young rat. We developed a new cannulation procedure which accomplishes these goals. Infant rats were removed from their mother on postnatal day 13 and fitted with a cannula that opened into the oral cavity through the hard palate. Liquid diet was administered by an infusion pump through the cannula for the subsequent 5 days. Growth was assessed by daily measures of body and organ weight. The results indicate that from postnatal day 13 on, the palate cannula can allow the continuation of normal growth patterns and eliminates certain complicating factors associated with other forms of artificial raising.

Animals↗
PubMed1988

Nutritional influences on adrenal chromaffin cell development: comparison with central neurons.

Neurotransmitter systems in the developing brain are generally protected from growth retardation associated with nutritional deprivation. To investigate if such protective mechanisms extend to similar tissues in the peripheral sympathetic system, maturation of the chromaffin cells of the adrenal medulla and development of their centrally derived splanchnic innervation were evaluated in rats whose nutritional status had been altered during the neonatal period by increasing (16-17 pups/litter) or decreasing (five to six pups/litter) the litter size from the standard (11-12 pups/litter). Ontogeny of adrenal catecholamine stores and activities of catecholamine-biosynthetic enzymes tyrosine hydroxylase and phenylethanolamine N-methyltransferase were monitored, along with activity of choline acetyltransferase, a marker enzyme for the preganglionic neurons innervating the chromaffin cells. Neonatal nutritional deprivation slowed body weight gain and retarded development of the chromaffin cells, as evidenced by subnormal catecholamine stores, tyrosine hydroxylase and phenylethanolamine N-methyltransferase activities. The effects persisted despite the complete recovery of body weights postweaning. The developmental alterations were not caused by overcrowding stress, as plasma corticosterone levels were not elevated in the large litter group. Neonatal nutritional enrichment promoted body weight gain but failed to enhance development of adrenal catecholamines; tyrosine hydroxylase and phenylethanolamine N-methyltransferase activities were elevated only in the preweaning period. In contrast to effects on the chromaffin cells, altered neonatal nutritional status had only minor, transient effects on the development of the centrally derived cholinergic innervation of the adrenal and produced only small changes (less than 10%) in brain tyrosine hydroxylase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1988

Activation of the adrenal cortex or the peripheral sympatho-adrenomedullary system does not necessarily influence milk ejection in the rat.

Following a 5-h isolation period, primiparous rats have the same milk supply on days 8/9 and 13/14 post partum, yet in response to suckling they release a greater amount of milk at the latter time. Inasmuch as stress is known to inhibit lactation and handling of the pups is stressful to the dams, the question arose as to whether separation from pups before nursing constitutes a greater stress for the dam at the earlier stage of lactation. This possibility was explored in the present study: As an index of stress, changes in plasma corticosterone were measured from chronically cannulated dams. In addition, the role of adrenal hormones and the peripheral sympathetic nervous system in the regulation of milk ejection under these experimental conditions was assessed following bilateral adrenalectomy and treatment with pentolinium, a ganglionic blocker which does not cross the blood-brain barrier. Corticosterone pellets were implanted subcutaneously following adrenalectomy in order to maintain proper lactation. From the results obtained, lactators demonstrated a greater increase in plasma adrenocorticosteroid levels in response to nursing on day 8/9 than on day 13/14 post partum, but milk yield was significantly less at the earlier than at the later stage of lactation. Adrenalectomy in conjunction with corticosterone replacement pellets did not alter milk supply or milk release. The subsequent treatment with pentolinium did not affect milk ejection. Pups still ingested less milk on day 9 than on day 13/14. It is suggested here that the isolation/suckling condition imposed on lactators may be more stressful earlier in lactation. Inasmuch as removal of the adrenal hormones along with ganglionic blockade did not modify the amount of milk ingested by the pups, it is concluded that the smaller milk release observed on day 9 post partum does not result from a direct suppression by the adrenal hormones or by the peripheral sympathetic nervous system on milk ejection.

Adrenal Cortex↗
PubMed1988

Role of sympathetic neurons in biochemical and functional development of the kidney: neonatal sympathectomy with 6-hydroxydopamine.

Renal sympathetic function develops over the first 3 weeks of postnatal life in the rat. In the current study, the effects of neonatal sympathectomy with 6-hydroxydopamine were examined on renal biochemical and functional development. The completeness and persistence of sympathetic nerve loss were confirmed by direct measurement of norepinephrine levels and turnover. Evidence was obtained for adverse effects on cellular maturation, as shown by perturbations in the ornithine decarboxylase/polyamine system, which is controlled partially by beta adrenergic input and which regulates macromolecule synthesis in developing cells. A later phase of 6-hydroxydopamine-induced alterations in renal development was seen during the period in which synaptogenesis is prominent and sympathetic tone is high (end of the 2nd postnatal week to end of the 3rd week): the denervated kidneys displayed supersensitivity of beta adrenergically mediated cyclic AMP responses without changes in receptor binding. The alterations in biochemical indices of cellular maturation were accompanied by abnormalities of renal function. 6-Hydroxydopamine caused an increase in the fractional excretion of sodium and deficits in physiological responsiveness of the kidney to a vasopressin analog. Later on, alterations in glomerular filtration rate and basal urinary osmolality also were prominent. These results indicate that neonatal sympathectomy has an adverse effect on the biochemical and functional development of the kidney.

Animals↗
PubMed1988

Neonatal central catecholaminergic lesions with intracisternal 6-hydroxydopamine: effects on development of presynaptic and postsynaptic components of peripheral sympathetic pathways and on the ornithine decarboxylase/polyamine system in heart, lung and kidney.

Peripheral sympathetic neurons are thought to provide trophic regulatory signals for development of adrenergic target tissues. In the current study, we destroyed central catecholaminergic pathways in the neonatal rat by intracisternal administration of 6-hydroxydopamine, which compromises sympathetic tone without ablating peripheral nerve terminals. Measurements of norepinephrine levels and turnover confirmed the effectiveness of the treatment in projections to heart, lung and kidney. The impairment of sympathetic tone was associated with a deficit in cardiac beta adrenergic receptor binding capabilities; in contrast, binding sites in the lung were unaffected and renal receptors were up-regulated. Similarly, intracisternal administration of 6-hydroxydopamine produced tissue-selective alterations in ornithine decarboxylase activity and levels of the polyamines. These results support the view that neural activity exerts an influence on the biochemical development of sympathetic target tissues; however, other trophic factors may derive from the presence of intact nerve terminals themselves, as distinct from activity.

Animals↗
PubMed1988

Trophic control of lung development by sympathetic neurons: effects of neonatal sympathectomy with 6-hydroxydopamine.

The onset of peripheral sympathetic neuronal function is thought to provide trophic regulatory signals for development of adrenergic target tissues. In the current study, we examined the effects on lung development of neonatal sympathectomy with 6-hydroxydopamine. The completeness of the lesion and effectiveness in reducing sympathetic input to the tissue were confirmed by direct measurement of norepinephrine levels and turnover. Despite the denervation, no evidence of beta-receptor up-regulation was found; in fact, receptor binding sites tended to be reduced throughout development. The cyclic AMP response to isoproterenol challenge was initially suppressed in the lesioned animals, but became supersensitive even in the face of reduced receptor binding capabilities. Evidence was also obtained for ontogenetic abnormalities in the ornithine decarboxylase/polyamine system, which is partially controlled by beta-adrenergic input and which regulates macromolecule synthesis in replicating and differentiating cells. Eventually, the alterations were reflected in aberrant developmental patterns of DNA, RNA and protein in the lung. These results indicate that sympathetic neurons influence the biochemical development of the lung and may serve to program permanently the relationships among receptor sites, receptor coupling to cellular function, and control of cell maturation.

Animals↗
PubMed1987

Central and sympatho-adrenal responses to insulin in adult and neonatal rats.

In the mature rat, subcutaneous administration of insulin (0.02 IU/g body wt.) produced hypoglycemia and a profound activation of the sympatho-adrenal pathway, as indicated by a marked depletion of adrenal catecholamines. Cellular glucopenia caused by administration of 2-deoxyglucose also produced a sympatho-adrenal response. In contrast, in 2-day-old rats, the systemic injection of insulin evoked only a small depletion of catecholamines even though severe hypoglycemia was present, and 2-deoxyglucose also produced a diminished response. The central administration of insulin at an equivalent dose (0.02 IU/g brain) stimulated brain ornithine decarboxylase activity in both neonates and adults, but was ineffective in evoking hypoglycemia or adrenal catecholamine release. These results suggest that: (a) direct interaction of insulin with its receptors in the central nervous system is not required for activation of the sympatho-adrenal pathway, and (b) the lack of sensitivity of neonatal adrenal catecholamine release to subcutaneous administration of insulin is likely associated with immaturity of splanchnic neurotransmission rather than with absence of central insulin receptors or impaired peripheral responsiveness to insulin.

Adrenal Cortex↗
PubMed1987

Central adrenergic receptor changes in the inherited noradrenergic hyperinnervated mutant mouse tottering.

Adrenergic receptor binding characteristics were analyzed in the mutant mouse tottering (tg/tg), a single gene locus autosomal recessive mutation causing hyperinnervation by locus coeruleus neurons of their target regions, which results in epilepsy. Instead of the expected down-regulation of receptors due to the hyperinnervation, both [3H]prazosin (alpha 1-receptor) and [125I]iodopindolol (beta-receptor) binding were normal in the tg/tg hippocampus, spinal cord and slightly increased in the cerebellum. This lack of postsynaptic receptor modulation in the target cells, combined with increased levels of norepinephrine due to the aberrant axon growth, may the critical factors in the expression of the abnormal spike-wave absence seizures in the tg/tg mouse.

Animals↗
PubMed1987

T cell-derived factor alone or in combination with immunosuppressive drugs augments prolongation of allogeneic skin graft survival in mice receiving donor-specific transfusion.

Limiting dilution cytotoxicity or proliferation assays were performed with cells taken from A/J mice pretransfused with BALB/c blood. The data obtained indicate that donor-specific transfusion decreased both the frequency of reactive precursors and their proliferative potential after activation. Additional studies implied that these changes may be associated with a serum- or cell-mediated antigen-specific suppressive mechanism. Further manipulations aimed at preferentially sparing or enhancing the activity of suppressor T cells prolonged skin graft survival in pretransfused mice and led to the presence of suppressor T cells in the spleen of such mice, which were active upon adoptive transfer. These manipulations included the use of pretransplant donor-specific transfusion, administration of ALS or cyclosporin-A, or the use of posttransplant injection with a T suppressor activating factor (SAF). Optimum graft survival was associated with combined treatment when using transfusion, SAF, and cyclosporin-A.

Animals↗
PubMed1987

The clinical diagnosis of Alzheimer's disease.

Clinical and pathologic diagnoses are compared in 65 patients who had dementia and who had been studied longitudinally during life. The sensitivity of diagnosis for dementia of the Alzheimer type (DAT) without any other diagnosis was 87%, and the specificity was 78%. The ischemic scale score did not discriminate well between patients with pure multi-infarct dementia and those with both DAT and multi-infarct dementia. However, 35 of 38 cases of pure DAT had a score of 4 or less on the ischemic scale.

Adult↗
PubMed1987

Interobserver variation in computed tomography of the brain.

As part of the University of Western Ontario Dementia Study, the computed tomographic brain scans of 16 patients were reviewed by three neuroradiologists. The size of the ventricles and sulci were rated using a six-point scale. Infarction and white matter changes were assessed in accordance with specified criteria. The interobserver correlations in this small series were statistically significant in 17 of 20 items, and good or acceptable for infarction, leuko-araiosis, and ventricular size. It is suggested that the use of rigid criteria for the definition of abnormality helps to promote interobserver agreement.

Brain↗