Biomedical subjects

W Tsai

Publications and source records attributed to W Tsai.

29 records · Page 2Linked to original sources

PubMed1997

Quality of life consequences of sleep-disordered breathing.

Sleep-disordered breathing occurs in approximately 2% to 4% of the adult population and includes conditions in which patients stop breathing completely (apnea) or have marked reductions in airflow (hypopnea) during sleep. Typical symptoms of sleep apnea include snoring, restless sleep, excessive daytime somnolence, nocturnal enuresis, irritability, depression, memory deficits, inability to concentrate, and decreased alertness. The clinically relevant outcomes of these symptoms include impairment in work efficiency, increased automobile accident rates, and decrements in quality of life. Treatment of sleep apnea, primarily with continuous positive airway pressure, reduces sleepiness and improves mood disturbances, neurocognition, and performance. Traditional measurements of sleep apnea severity do not correlate well with current tests and scales that are used to quantify alterations in alertness, performance, quality of life, or sleepiness. A disease-specific quality of life scale has been developed following patient and physician interviews and literature reviews. The Calgary Sleep Apnea Quality of Life Index is expected to capture aspects of quality of life important to sleep apnea patients, such as cognitive function, performance, and mood, that could be improved with appropriate treatment of sleep-disordered breathing.

Accidents, Traffic↗

PubMed1996

Structure of the human gene encoding the protein repair L-isoaspartyl (D-aspartyl) O-methyltransferase.

The protein L-isoaspartyl/D-aspartyl O-methyltransferase (EC 2.1.1.77) catalyzes the first step in the repair of proteins damaged in the aging process by isomerization or racemization reactions at aspartyl and asparaginyl residues. A single gene has been localized to human chromosome 6 and multiple transcripts arising through alternative splicing have been identified. Restriction enzyme mapping, subcloning, and DNA sequence analysis of three overlapping clones from a human genomic library in bacteriophage P1 indicate that the gene spans approximately 60 kb and is composed of 8 exons interrupted by 7 introns. Analysis of intron/exon splice junctions reveals that all of the donor and acceptor splice sites are in agreement with the mammalian consensus splicing sequence. Determination of transcription initiation sites by primer extension analysis of poly(A)+ mRNA from human brain identifies multiple start sites, with a major site 159 nucleotides upstream from the ATG start codon. Sequence analysis of the 5'-untranslated region demonstrates several potential cis-acting DNA elements including SP1, ETF, AP1, AP2, ARE, XRE, CREB, MED-1, and half-palindromic ERE motifs. The promoter of this methyltransferase gene lacks an identifiable TATA box but is characterized by a CpG island which begins approximately 723 nucleotides upstream of the major transcriptional start site and extends through exon 1 and into the first intron. These features are characteristic of housekeeping genes and are consistent with the wide tissue distribution observed for this methyltransferase activity.

Base Sequence↗

PubMed1996

The pneumoconioses.

The stringent industrial hygiene regulations that have been introduced in North America, Europe, and Australasia have led to a decline in the incidence and prevalence of silicosis, coal workers' pneumoconiosis, and asbestosis. Although new cases of asbestosis are not occurring, an appreciable number of mesotheliomata are still being diagnosed, and there has yet been little, if any, decline in the latter tumor. These new cases are nearly entirely due to exposure to amphiboles in the 1940s and 1950s. It is expected that by about the year 2000 the incidence of mesothelioma will begin to decrease in the United States and Canada. Meanwhile there is an undue preoccupation with more and more sensitive methods of detecting asbestosis, silicosis, and coal workers' pneumoconiosis, eg, magnetic resonance imaging, bronchoalveolar lavage, and so forth. Much effort is being made in trying to detect disease in groups of workers with extremely low exposures and no symptoms. Smaller and smaller effects are being detected, with the ultimate aim appearing to be detecting nothing at all. Efforts should be made at surveying other populations exposed to agents that have recently been introduced and that could conceivably have long-term effects.

Asbestos, Amphibole↗

PubMed1996

Adaptations of intestinal nutrient transport to chronic caloric restriction in mice.

Lifelong caloric restriction increases median and maximum life span and retards the aging process in many organ systems of rodents. Because the small intestine absorbs a reduced amount of nutrients each day, does lifelong caloric restriction induce adaptations in intestinal nutrient transport? We initially compared intestinal transport of sugars and amino acids between 24-mo-old mice allowed free access to food [ad libitum (AL)] and those provided a calorically restricted [40% less than ad libitum (CR)] diet since 3 mo of age. We found that CR mice had significantly greater transport rates for D-glucose, D-fructose, and several amino acids and had significantly lower villus heights. Total intestinal absorptive capacities for D-glucose, D-fructose, and L-proline were each 40-50% greater in CR mice; absorptive capacity normalized to metabolic mass (body weight 0.75) was approximately 80% greater in CR mice. Comparison of uptakes in aged AL and CR mice with previously published results in young AL mice suggests that caloric restriction delays age-related decreases in nutrient transport. In contrast to published studies in hibernation and starvation, chronic caloric restriction enhances not only uptake per milligram but also uptake per centimeter. We then switched 24-mo-old AL mice to a calorie-restricted diet for 1 mo and found that short-term caloric restriction has no effect on intestinal nutrient transport, intestinal mass, and total absorptive capacity. Thus chronic but not short-term caloric restriction increases intestinal nutrient transport rates in aged mice, and the main mechanism underlying these increases is enhanced transport rates per unit intestinal tissue weight.

Adaptation, Physiological↗

PubMed1996

Regulation of somatic growth and the somatotropic axis by gonadal steroids: primary effect on insulin-like growth factor I gene expression and secretion.

The site-specific regulation of somatic growth by sex steroids is poorly understood. The aim of the present study was to assess the influence of 17 beta-estradiol (E2) and 5 alpha-dihydrotestosterone (DHT) on somatic growth and pituitary GH and hepatic insulin-like growth factor I (IGF-I) secretion and synthesis in the adult female rat. Animals (200-250 g) underwent sham surgery or bilateral ovariectomy. Some ovariectomized (OVX) rats were given sc implants that provided almost physiological female E2 (OVX/E2) and male DHT (OVX/DHT) levels. Animals were killed 3, 7, 14, and 26 days later. Body weight gain was calculated, and pituitary GH content, pituitary GH messenger RNA (mRNA) levels, plasma GH, and circulating IGF-I concentrations were measured. Levels of hepatic IGF-I mRNA were measured at 26 days. Ovariectomy increased body weight gain (P < 0.001) in parallel with a significant elevation in plasma IGF-I (P < 0.001). Replacement of E2 markedly suppressed somatic growth (P < 0.001), plasma IGF-I concentrations (P < 0.001), and liver IGF-I gene expression (P < 0.002). However, circulating GH concentrations were high in OVX/E2 animals (P < 0.001), whereas pituitary GH stores were significantly attenuated (P < 0.05). In contrast, DHT exposure increased body weight gain (P < 0.001), circulating IGF-I concentrations (P < 0.05), and steady state hepatic IGF-I mRNA levels (P < 0.05). Pituitary GH stores were markedly elevated (P < 0.001) in DHT-treated animals, but circulating GH levels remained very low. Pituitary GH mRNA rose transiently at 7 days in OVX and OVX/E2 rats, but no consistent changes between the groups were observed thereafter. We conclude that 1) gonadal steroids have disparate effects on somatic growth in female rats, with E2 suppressing and DHT stimulating body weight gain; 2) these effects are likely to be primarily mediated at the level of IGF-I synthesis and secretion; and 3) changes in pituitary GH content and secretion probably reflect normal adjustment to changes in the intensity of IGF-I negative feedback.

Animals↗

PubMed1994

Amino acid polymorphisms of the human L-isoaspartyl/D-aspartyl methyltransferase involved in protein repair.

We have analyzed DNA from three exons of the human protein-L-isoaspartate(D-aspartate) O-methyltransferase gene in 30 individuals. We present evidence for two polymorphisms in these regions that result in amino acid changes. At a site corresponding to amino acid position 119, we find the ATA codon for Ile at a frequency of 0.77 and the GTA codon for Val at a frequency of 0.23. At the site corresponding to amino acid position 205, we find the AAG codon for Lys at a frequency of 0.98 and the AGG codon for Arg at a frequency of 0.02. These amino acid changes may affect the ability of this enzyme to recognize and catalyze the first step in the repair of proteins spontaneously damaged in the aging process.

Adult↗

PubMed1994

Effect of L-glutamic acid on acid secretion and immunohistochemical localization of glutamatergic neurons in the rat stomach.

Glutamatergic neurons in the rat stomach were localized immunohistochemically using antibodies against L-glutamate (L-Glu) as well as glutamate synthesizing enzyme, glutaminase (GLNase). Myenteric ganglia and nerve bundles in the circular muscle and the longitudinal muscle were found to contain GLU- and GLNase-positive nerve fibers, while submucosa and mucosa were devoid of glutamatergic innervation. The distribution of glutamatergic neurons and their processes in both myenteric ganglia and circular muscle is heterogeneous within the stomach. The effect of L-Glu on gastric acid secretion was investigated on an everted preparation of isolated rat stomach. L-Glu at 10(-7) and 10(-8) M alone had no effect on acid secretion. It was found that the oxotremorine-, histamine-, or gastrin-stimulated acid secretion was markedly reduced by L-Glu at 10(-8) M, whereas L-Glu had little effect on the acid secretion stimulated by dimethyl-phenylpiperazinium (DMPP) at this concentration. However, at higher concentration, e.g., 10(-7) M, L-Glu also markedly reduced DMPP-induced acid secretion. Among L-Glu receptor agonists tested, quisqualic acid (QA) is most potent, followed by kainic acid (KA) and N-methyl-D-aspartic acid (NMDA) in inhibiting oxotremorine-stimulated acid secretion. Furthermore, this inhibitory effect of L-Glu on oxotremorine-stimulated acid secretion is blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a specific non-NMDA receptor antagonist. All these results suggest that glutamatergic neurons are involved in the modulation of gastric acid secretion via ionotropic QA/KA receptors, probably through openings of Ca2+ channels.

Animals↗

PubMed1994

Negative feedback regulation of pulsatile growth hormone secretion by insulin-like growth factor I. Involvement of hypothalamic somatostatin.

To investigate the mechanisms of the negative feedback inhibition of growth hormone (GH) secretion by IGF-I, we studied parameters of GH pulsatility in six normal, fed men before and during a 48-h infusion of recombinant human IGF-I (rhIGF-I) (10-15 micrograms/kg per h). Plasma levels of IGF-I increased from the baseline value of 163.5 +/- 9.3 micrograms/liter (mean +/- SE) to a new steady state of 452.0 +/- 20.9 micrograms/liter during the infusion. Plasma GH concentrations were measured every 10 min for 24 h during both saline and rhIGF-I infusions using a sensitive chemiluminescent assay. Overall, GH concentrations were suppressed during the rhIGF-I infusion by 85 +/- 3%, mainly by attenuating spontaneous GH pulse amplitude (77 +/- 4% suppression). The apparent GH pulse frequency was attenuated from 7.8 +/- 0.9 to 4.7 +/- 0.6 pulses/24 h (P = 0.006). Administration of rhIGF suppressed GH responses to exogenous GH-releasing hormone by 82 +/- 3%, and thyroid-stimulating hormone responses to thyrotropin-releasing hormone were also suppressed by 44 +/- 9%. This constellation of hormonal effects is most compatible with the rhIGF-I-induced stimulation of hypothalamic somatostatin secretion.

Adolescent↗

PubMed1993

Action of myenteric GABAergic neurons in the guinea pig stomach.

GABAergic neurons in the guinea pig stomach were localized immunocytochemically using antibodies against its synthesizing enzyme, L-glutamate decarboxylase (GAD). Numerous ganglion cells and nerve bundles in the myenteric plexus were found to be GAD-positive, while the longitudinal muscle, submucosa and mucosa were largely devoid of GABAergic innervation. The distribution of GABAergic neurons and their processes in both myenteric ganglia and circular muscle is rather uneven throughout the stomach. GABA elicited contraction of the longitudinal fashion (LF) strips of the body and antrum of guinea pig stomach in a concentration-dependent fashion with a maximal response at 10(-7) M and 10(-5) M, respectively. GABA-induced contraction appears to be mediated by the GABAA receptor and not the GABAB receptor, since the action is blocked by bicuculline, a GABAA receptor antagonist. Furthermore, GABAA agonists e.g. muscimol produced even stronger responses than GABA itself while GABAB agonist, (-)baclofen had no effect in eliciting muscle contraction. The GABAA receptor is desensitized by prolonged exposure to its agonists such as GABA and muscimol. However, no such desensitization was observed for the muscarinic cholinergic receptor. The GABA action in eliciting smooth muscle contraction seems to involve two components, one is scopolamine and tetrodotoxin (TTX) sensitive, and the other one is insensitive to scopolamine and TTX. It is proposed that the scopolamine- and TTX-sensitive component acts through a direct or indirect interaction between GABAergic and cholinergic neurons whereas the scopolamine- and TTX-insensitive component acts directly upon the smooth muscle.

Animals↗

PubMed1991

Isospora belli infection in a patient with Hodgkin's disease: report of a case.

A 42-year-old woman with a history of documented Hodgkin's disease for 1 year presented with watery diarrhea for 6 months. She developed watery diarrhea following recurrence of the underlying disease and use of herbs. After institution of chemotherapy, watery diarrhea persisted despite remission of the underlying disease. Stool cultures and examinations for several pathogens were negative. Later, oocysts of Isopora belli were identified in the stool. The immunological status was typical of patients with Hodgkin's disease. However, HTLV-1 seropositivity and an intact skin test for delayed hypersensitivity were noted. Institution of co-trimoxazole led to prompt resolution of the gastrointestinal symptoms within the ensuing 24 hours. Later she developed recurrent isosporiasis after chemotherapy for the underlying disease, but institution of co-trimoxazole again resolved the symptoms. She remains on maintenance therapy with co-trimoxazole. Isospora belli infection should be considered in opportunistic infections in patients with Hodgkin's disease.

Adult↗

PubMed1978

Benzocaine diffusion from polyethylene glycol through human stratum corneum.

The diffusion, penetration, and surface effects of benzocaine incorporated in various polyethylene glycol ointment bases through human stratum corneum were studied. Benzocaine diffusion was measured by following the benzocaine concentration in the receiving compartment of a diffusion cell. The ointment was placed in the other cell compartment and was separated from the receiving compartment by sheets of human stratum corneum. Surface effects were monitored by scanning electron micrographs of the stratum corneum. Results showed a decrease in drug diffusion in the presence of relatively high amounts of the lower molecular weight portions of polyethylene glycol. Scanning electron microscope studies showed that both benzocaine and polyethylene glycol affect the surface structure of the stratum corneum. Thermal analysis indicated that benzocaine dissolves in polyethylene glycol.

Adult↗