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Biomedical subjects

W Chin

Publications and source records attributed to W Chin.

At least 37 records · Page 2Linked to original sources

Abnormal spermatogenesis in RXR beta mutant mice.

We have generated mouse lines in which the RXR beta gene was disrupted by homologous recombination. Approximately 50% of the RXR beta homozygous mutants died before or at birth, but those that survived appeared normal except that the males were sterile, owing to oligo-astheno-teratozoospermia. Failure of spermatid release occurred within the germinal epithelium, and the epididymis contained very few spermatozoa that, in addition, exhibited abnormal acrosomes and tails. There was a progressive accumulation of lipids within the mutant Sertoli cells, which were histochemically characterized as unsaturated triglycerides. In old mutant males, progressive degeneration of the germinal epithelium occurred, ending with the formation of acellular lipid-filled tubules. The selective expression of RXR beta in Sertoli cells, together with the timing of appearance of the histological abnormalities, suggests that the primary defect resulting from the mutation resides in these cells.

Animals↗

Three novel mutations and two variants in the gene for Cu/Zn superoxide dismutase in familial amyotrophic lateral sclerosis.

Autosomal dominant inheritance is exhibited by about 10% of cases of amyotrophic lateral sclerosis (ALS), a paralytic disorder characterized by the death of motor neurons in the brain and spinal cord. A subgroup of these familial cases are linked to mutations in the gene which codes for Cu/Zn superoxide dismutase (SOD1). We report three additional mutations occurring in the SOD1 gene in ALS patients and two single base pair variant changes. The single base pair change in an ALS family causes a glycine 93 to valine substitution, which is the fifth distinct amino acid change reported for the glycine 93 residue. One missense mutation in exon 5 would substitute neutral valine for the negatively-charged aspartate 124 (aspartate 124 to valine). An individual with an apparently sporadic case of ALS carries a three base pair deletion in exon 5 of the SOD1 gene. These three mutations bring to 38 the total number of distinct SOD1 mutations associated with familial ALS.

Amyotrophic Lateral Sclerosis↗

Scintigraphic and electrocardiographic evidence of silent coronary artery disease in asymptomatic hypertension: a case-control study.

OBJECTIVES: This study was conducted to determine the incidence of physiologically significant coronary artery disease in a group of asymptomatic high risk men with essential hypertension and to assess the validity of noninvasive tests in a subset of these patients undergoing coronary arteriography. METHODS: Two hundred twenty-six asymptomatic men (mean age 61 +/- 8 years) with essential hypertension and no clinical evidence of coronary artery disease but with at least one additional coronary risk factor were studied prospectively. Fifty age- and risk factor-matched normotensive subjects were evaluated as a control group. After a minimum of 4 days without medication, subjects underwent stress thallium-201 scintigraphy, exercise and 48-h ambulatory electrocardiography, and echocardiography. Coronary angiography was performed in a subset of 34 (40%) of 84 patients with one or more positive test results. RESULTS: A positive thallium-201 scintigram (18% vs. 6%; odds ratio 3.4, confidence interval 0.95 to 10.8, p = 0.056), exercise electrocardiograms (ECGs) (37% vs. 13%; odds ratio 4.1, confidence interval 1.5 to 11.2, p < 0.003) and ambulatory ECG (15% vs. 0%, p < 0.05) were more common in the hypertensive group than in the control group. In the cohort undergoing coronary angiography, thallium-201 scintigraphy was both sensitive and specific for epicardial atherosclerotic coronary disease (90% and 79%, respectively), but positive exercise and ambulatory ECGs occurred frequently in the absence of significant coronary stenoses. In the 39% of hypertensive patients who had mild to moderate left ventricular hypertrophy, positive exercise and ambulatory ECGs occurred at a higher rate. CONCLUSIONS: These findings suggest that physiologically significant coronary artery disease occurs more frequently in asymptomatic hypertensive men than in comparable normotensive control subjects. In the subgroup undergoing coronary arteriography, reversible scintigraphic defects were both sensitive and specific for diagnosing epicardial coronary artery disease, but exercise and ambulatory ECGs appeared to yield frequent false positive results, especially when left ventricular hypertrophy was present. These results indicate that patients with "silent" coronary artery disease can be identified among high risk hypertensive patients, but the appropriate application of such screening in clinical practice remains to be determined.

Adult↗

[The effects of intracoronary injection of nitroglycerin on the coronary circulation: evaluation using a Doppler catheter].

To evaluate the effects of intracoronary injection of nitroglycerin (NTG) on the coronary circulation, we measured the flow velocity of the coronary artery using a Doppler catheter. The Doppler catheter was introduced into the region proximal to the left anterior descending artery (LAD) via an 8F guide catheter positioned at the orifice of the left coronary artery. We measured the flow velocity at a point of 3 mm distal to the catheter tip. One mg (2 ml) of NTG was injected via the 8F guide catheter for 10 sec, followed by injection of 3 ml of normal saline. Then the increasing rate of the diastolic coronary flow velocity in the LAD was calculated. Five ml of iopamidol (dye) was also injected for comparison. The subjects consisted of 14 normal persons (G-N), and 12 patients with angina pectoris accompanying critical stenoses of the LAD, who had no ECG changes or no abnormalities by left ventriculography. The subjects with angina pectoris were subclassified as 90% stenoses (G-A: 5 patients), and 99% stenoses (G-B: 7 patients) in the LAD. 1. After intracoronary injection of NTG, the aortic pressure dropped to various degrees in G-N. In 7 of the normal subjects, who had less than a 20% aortic pressure drop, the increased diastolic flow velocity was more rapid than the control diastolic flow velocity 30 sec after the peak velocity.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Lymphatic removal of dialysate from the peritoneal cavity of anesthetized sheep.

Several investigators have suggested that the lymphatic circulation reduces ultrafiltration in continuous ambulatory peritoneal dialysis (CAPD). The purpose of this study was to assess lymphatic drainage of the peritoneal cavity directly in anesthetized sheep under dialysis conditions. Lymph was collected from the caudal mediastinal lymph node and the thoracic duct, both of which are involved in the lymphatic drainage of the ovine peritoneal cavity, and from the prescapular lymph node, which is not involved in peritoneal lymphatic drainage. Fifty ml/kg volumes of a mildly hypertonic dialysis solution (Dianeal 1.5%) containing 25 microCi 125I-human serum albumin were instilled into the peritoneal cavity, and lymph flows and the appearance of labeled protein in the lymphatic and vascular compartments were monitored for six hours. Following the instillation of dialysis fluid there was a tendency for lymph flow rates from the thoracic duct to increase but these changes were not significant. However, flow rates from the caudal lymphatic demonstrated significant increases, especially in the final three hours of the monitoring period. Only about 8% of the radiolabeled albumin was removed from the peritoneal cavity over six hours (that is, 92% was left in the peritoneal space). Of the albumin removed, approximately 17% of this was drained by abdominal visceral lymphatics into the thoracic duct. About 25% passed through the diaphragm into the caudal mediastinal lymph node and into efferent lymph. Since the efferent lymphatic duct of the caudal mediastinal node empties directly into the thoracic duct, about 42% of all protein removed from the peritoneal cavity of the sheep was ultimately transported to the thoracic duct.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

DNA methylation in specific cells of rat liver by N-nitrosodimethylamine and N-nitrosomethylbenzylamine.

Dose-response curves for the O6-methylation of guanine in the hepatic DNA of Wistar and Sprague-Dawley rats were determined after administration of N-nitrosomethylbenzylamine (NMBzA) or N-nitrosodimethylamine (NDMA). Similar results were obtained for both rat strains but methylation of hepatic DNA by NDMA was approximately 9-fold more efficient than with NMBzA when doses were compared on a molar basis. Comparison by immunohistochemical analysis of the distribution of nuclei containing O6-methylguanine within the liver lobules showed that both agents tended to alkylate cells close to the central veins at the lower doses. With increasing doses, the band width of alkylated cells around the central vein increased, spreading in the case of NDMA virtually into the portal zones, whereas with NMBzA the zone of alkylated nuclei reached little more than halfway from the central vein to the portal zone. These differences in the distribution of alkylated cells may explain the differing hepatic responses to these two nitrosamines.

Animals↗

Lymphatic drainage of the peritoneal cavity in sheep.

Lymphatic drainage of the peritoneal cavity has been investigated in anesthetized sheep. Studies involving intraperitoneal administration of a complex of Evans blue dye and bovine serum albumin demonstrated the existence of three anatomically distinct pathways. In the first pathway, dye is removed from the peritoneal cavity by diaphragmatic lymphatics that pass into caudal sternal lymph nodes. Efferent lymphatics from these nodes transport the material to cranial sternal lymph nodes. Efferent cranial sternal lymphatics then convey the material either directly or indirectly, via tracheal lymphatic trunks, to the right lymph duct. In the second pathway, the complex is transported from the peritoneal cavity by diaphragmatic lymphatics that pass into the caudal mediastinal lymph node. Efferent lymphatic ducts from this node transport the material to the thoracic duct. The third pathway appears to involve transport of the dye across the mesothelial lining of the abdominal viscera and removal from the interstitium by afferent visceral lymphatics. Material taken up in this manner is ultimately transported to the thoracic duct by efferent visceral lymphatics. Experiments involving measurements of lymphatic absorption of 125I-labeled human serum albumin from the peritoneal cavity indicated that, over the 6-h period studied, 4.55 +/- 1.20 and 1.43 +/- 0.56% of the injected tracer could be recovered in thoracic duct lymph and caudal mediastinal efferent lymph, respectively, and the sum of these values represented 26% of the recovered radioactivity. On the other hand, 16.95 +/- 6.93% of the injected radioactivity could be found in the blood over the same period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Toxicity of N-nitrosodimethylamine, N-nitrosomethylbenzylamine, and 1,2-dimethylhydrazine in isolated rat hepatocytes.

N-Nitrosodimethylamine and 1,2-dimethylhydrazine were shown to injure lethally primary monolayer cultures of rat hepatocytes only after incubation periods in excess of 24 hr. The toxic action of these agents, therefore, mimics the time dependency of their hepatoxicity in vivo. The viability of hepatocytes treated with N-nitrosomethylbenzylamine was not different from controls at times up to 54 hr following treatment, a result which is also consistent with the inability of this compound to produce hepatotoxicity in vivo.

1,2-Dimethylhydrazine↗

[Tachycardia-induced cardiomyopathy: a case report].

A 30-year-old man with chronic sustained ventricular tachycardia (VT) lasting more than seven years was treated with propranolol, 30 mg/day. This resulted in controlled cardiac rates of 90 to 130/min during sleep, and 100 to 195/min while awake. However, he experienced Adams-Stokes attacks twice, in September and December, 1986. During the second attack, ambulatory heart monitoring showed his VT rate of 212/min. An electrophysiological study revealed that the VT focal point was in the lower-mid region of the interventricular septum in the right ventricle. The VT was characterized by abnormal enhanced automaticity. This VT could not be interrupted either by single or multiple combinations of antiarrhythmic drugs. Cardiac catheterization revealed a diffusely enlarged hypokinetic left ventricle, even at the rate of 120/min VT (EF 27%, C.I. 2.3 l/min/m2). Because of his severe hemodynamic state, we performed electrical catheter ablation successfully. After the ablation, his left ventricular wall motion gradually improved. Nine months after the ablation, his left ventricular diastolic dimension decreased from 64 to 48 mm and the left ventricular systolic dimension decreased from 57 to 28 mm on M-mode echocardiography, while ejection fraction increased from 27 to 73% on the left ventriculography. Bi-ventricular myocardial biopsy specimens obtained prior to the ablation revealed only cellular hypertrophy of varying degrees, and vacuole degeneration consistent with non-specific cardiomyopathy. However, nine months after the ablation, these findings were no longer present. Thus, this case was considered tachycardia-induced cardiomyopathy initiated by VT, lasting many years.

Adult↗

Failure of dipyridamole-thallium myocardial imaging to detect severe coronary disease.

Three patients referred for peripheral vascular surgery who died of coronary artery disease complications despite normal dipyridamole-thallium scans are discussed. Although recent literature has shown enthusiasm for this test in this clinical setting, the dipyridamole-thallium scans are not absolute and patients remain at risk for major coronary artery events. Careful clinical screening and awareness of the signs of left main coronary disease on thallium images are important in the evaluation of these patients.

Adult↗

T and B cells have similar recirculation kinetics in sheep.

T and B cells continually migrate around the body by recirculating between blood and lymph via lymphoid tissues. This is an important way of fostering the cell-cell interactions required for the initiation of an immune response. Data from previous studies of T and B cell recirculation, based on relatively complex approaches, have been interpreted as evidence that the recirculation of B cells is more sluggish than for T cells. We have shown from a study in sheep that this is not the case. Lymphocyte migration through both the intestine and the prescapular lymph node was analyzed by cannulating efferent lymphatics. The lymph cells were labeled in vitro with Hoechst 33342, or other fluorochromes, then injected i.v., and the rate of their recirculation into the lymph was determined by fluorescence microscopy. A multicolor immunofluorescence assay was used to classify each recirculated cell as either a T or B cell. This established that the T and B cells from intestinal lymph and from prescapular lymph recirculate with similar kinetics. The recovery of i.v. injected T and B cells was the same in prescapular lymph, but fewer injected B cells than T cells were recovered in intestinal lymph. Thus, although the recirculation kinetics are the same for T and B cells, the two populations are handled differently in intestinal tissues and a lymph node remote from the gut.

Animals↗

Malignant fibrous histiocytoma of prostate.

A prostatic tumor removed suprapubically in a sixty-three-year-old man was found to be a malignant fibrous histiocytoma. Various aspects of prostatic sarcomas and malignant fibrous histiocytomas are considered.

Histiocytoma, Benign Fibrous↗

A dual laser analysis of the migration of XRITC-labeled, FITC-labeled, and double-labeled lymphocytes in sheep.

Substituted rhodamine isothiocyanate (XRITC) has been used to study lymphocyte migration in sheep. After being labeled in vitro with XRITC, lymphocytes appeared in the efferent lymph of single lymph nodes with the same kinetics as cells labeled with fluorescein isothiocyanate (FITC). The recovery of intravenously injected XRITC-labeled cells was followed in lymph for several days. The kinetics and recoveries were compared with data obtained using FITC, chromium-51, and indium-111. XRITC was found to be a suitable label and, using dual laser (argon and krypton) flow cytometry, it could be analyzed simultaneously with FITC. In addition, it was possible to relabel FITC-stained cells with XRITC after they were recovered in lymph. The migratory characteristics of such double-labeled cells were not different from single-labeled cells.

Animals↗

Plasmodium fragile: inhibition of cultures by serum from rhesus monkeys immunized with homologous parasites.

Rhesus monkeys, Macaca mulatta, that had previously been immunized with the Nilgiri strain of Plasmodium fragile grown in culture, together with control monkeys with and without inoculation of Freund's adjuvant, were challenged with cultured parasites. After treatment with chloroquine, the monkeys were rechallenged. Serum specimens from three immunized monkeys caused a specific, dose-dependent inhibition of parasite growth in culture. Fifty percent inhibition of in vitro growth was obtained using 5% immune serum combined with 10% normal rhesus serum. The specific inhibitory component of immune serum was shown to be IgG antibody. Results of the study demonstrated that there is good correlation between the inhibitory activity of immune serum, parasite growth in vitro, the in vivo response to challenge, and the indirect fluorescent antibody titer.

Animals↗

Glucose-6-phosphate dehydrogenase deficiency in Southeast Asian refugees entering the United States.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited disorder of red blood cell metabolism. Affected individuals may suffer a severe hemolytic crisis when treated with primaquine, an antimalarial. A survey of 966 male Southeast Asian refugees determined that 50 (5.2%) were G6PD-deficient. This prevalence suggests that a G6PD assay should be performed prior to primaquine therapy in this high-risk population.

Adult↗