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Biomedical subjects

J Y Chan

Publications and source records attributed to J Y Chan.

At least 145 records · Page 8Linked to original sources
PubMed1986

Protective role of thiols in carcinogen-induced DNA damage in rat liver.

Biological thiols are known to play an important role in the detoxification of xenobiotics, including chemical carcinogens. To determine the influence of cellular thiols on carcinogen induction of hepatic DNA damage in the rat, diethylmaleate (DEM) administration was used to deplete intracellular glutathione (GSH). The effects of administration of the synthetic thiols, N-acetylcysteine (NAC) and alpha-mercaptopropionylglycine (alpha MPG), on the induction of DNA lesions were also examined. Pretreatment with DEM reduced liver GSH levels by greater than 70%. As assessed by the technique of alkaline elution, subsequent administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) resulted in DNA damage 4 h post MNNG treatment which was 4- to 8-fold greater than that induced in the livers of rats treated with MNNG alone. However, DEM pretreatment had little effect on the extent of DNA damage induced by methylnitrosourea (MNU). DEM alone did not cause any measurable DNA damage. Pretreatment with alpha MPG or NAC reduced MNNG-induced DNA damage by as much as 77%. In contrast, MNU-induced DNA damage was increased by alpha MPG treatment whereas NAC treatment was without effect. These results indicated that in the rat liver, the activity of some DNA alkylating agents may be modulated in varying degree by the concentration of intracellular thiols. These data support the notion that thiols play an important role in protection against carcinogen damage, and that synthetic thiols such as alpha MPG and NAC may be useful as anti-carcinogenic agents against certain carcinogens.

Acetylcysteine↗
PubMed1986

Activated (Ia+) T-lymphocytes and their subsets in autoimmune thyroid diseases: analysis by dual laser flow microfluorocytometry.

Peripheral blood lymphocytes of patients with autoimmune thyroid diseases were studied using monoclonal antibodies reacting with cell surface antigens of activated T-cells (Ia+T), as well as their helper-inducer (Ia+TH/I) and suppressor-cytotoxic (Ia+TS/C) subsets, using two-color dye labeling and dual laser activated cell sorter analyses. Compared to normal subjects, hyperthyroid Graves' disease patients had significantly higher percent Ia+T values in association with an increase in percent Ia+TH/I as well as a reduction in percent Ia+TS/C; whereas patients with hypothyroid Hashimoto's thyroiditis as well as those with postpartum thyroiditis studied in the hyperthyroid phase also had a significant but lesser increase in percent Ia+T-cells, but their percent Ia+TH/I subset was significantly decreased, whereas the percent Ia+TS/C subset was increased; and patients with toxic nodular goiter or factitious hyperthyroidism (nonimmunogenic causes of hyperthyroidism) had a significant increase in percent Ia+T-cells without a significant difference in their Ia+T subsets or their ratios in comparison to controls. These studies demonstrated the feasibility of detecting Ia+T-cells and their subset characteristics using two-color dye labeling and dual laser flow microfluorocytometric methodology. In both the active and treated phases of Graves' disease, Hashimoto's thyroiditis, and postpartum thyroiditis, the percent Ia+T-cells was increased compared to normal subjects, with the highest values occurring in hyperthyroid Graves' disease. Furthermore, patients with hyperthyroid Graves' disease had the opposite changes in percent Ia+TH/I and Ia+TS/C subsets as compared to patients with either untreated hypothyroid Hashimoto's disease or the hyperthyroid phase of postpartum thyroiditis, suggesting that the pathogenic mechanisms involved in Hashimoto's disease and the destructive hyperthyroidism of painless thyroiditis are similar, and that they are both distinctly different from that of hyperthyroid Graves' disease.

Adult↗
PubMed1986

Activated (Ia+) T-cells and their subsets in Graves' disease and Hashimoto's thyroiditis using dual laser flow microfluorocytometric analysis.

UNLABELLED: Lymphocytes from patients with Graves' disease and Hashimoto's thyroiditis were analysed directly by a dual laser-activated cell-sorter for the percentage of activated T-cells and their subsets using two-colour dye-labelling with monoclonal antibodies specific for antigens of Ia+ T-cells, as well as either their T-helper/inducer (TH/I) or T-suppressor/cytotoxic (TS/C) subsets. Compared to normal subjects, patients with hyperthyroid Graves' disease had a significantly (p less than 0.0001) higher percentage of activated (Ia+ Leu 4+) T-cells (7.8 +/- 1.9 versus 1.9 +/- 0.4), wherein their percentage of Ia+ Leu 3a+ (Ia+ TH/I) subset was significantly increased (p less than 0.001) and the percentage of Ia+ Leu 2a+ (Ia+ TS/C) subset decreased; patients with hypothyroid Hashimoto's thyroiditis also had a significant (p less than 0.001) increase in the percentage of Ia+ T-cells (4.3 +/- 0.6 versus 1.9 +/- 0.4), wherein their percentage of Ia+ TH/I was significantly reduced (p less than 0.001), while the percentage of the Ia+ TS/C subset was increased compared to normal. Following a return of thyroid status to euthyroidism, the percentage of Ia+ T-cells decreased in both Graves' and Hashimoto's thyroiditis patients, but remained significantly higher (p less than 0.001) than normal subjects, while the Ia+ TH/I and Ia+ TS/C subsets were no longer different. CONCLUSIONS: (1) the feasibility of enumerating Ia+ T-cells and their subsets in autoimmune thyroid diseases using two-coloured dyes and dual laser flow microfluorometric analytical techniques has been demonstrated. (2) Percentage increases in Ia+ T-cells have been demonstrated in both hyperthyroid Graves' and hypothyroid Hashimoto's which, following restoration to euthyroidism, decreased but still remained significantly higher than normal. (3) Patients with hyperthyroid Graves' and hypothyroid Hashimoto's disease were demonstrated to have the opposite phenotypic changes within activated T-cell subsets, thereby indicating that their pathogenic mechanisms are different.

Adult↗
PubMed1985

Post-partum hyperthyroidism.

The importance of recognizing the frequent occurrence of the destructive (i.e. PPT) and stimulatory (i.e. PGD) causes of PH have been discussed. The estimated prevalence of PH in several geographical regions of Japan, North America and Europe ranges from 2.0-5%. Although the autoimmune basis for GD has been well-established, the clinical and laboratory features of PPT as well as the alterations of humoral and cellular thyroidal immune parameters, the typical needle biopsy evidence of lymphocytic infiltration, and the association with HLA and Gm allotypes associated with the PPT syndrome, favour the view that it is also likely a variant form of subclinical ATD which becomes transiently more active post-partum. Post-partum transient hyperthyroidism with or without transient or permanent hypothyroidism and relapse of GD thyrotoxicosis have been observed in patients with or without a previous history of GD. Hence, an RAIU test is the preferred diagnostic test in differentiating between these two entities, especially in the absence of associated stigmata of GD. When the RAIU test is suppressed, other causes such as thyrotoxicosis factitia and iodine exposure should be excluded. Without an RAIU test, only a rapid and spontaneous resolution of post-partum hyperthyroidism, accompanied by laboratory confirmation of a subsequent hypothyroid phase, can indirectly facilitate the differentiation between PGD and PPT. In the first trimester of pregnancy, an increased FT4I has been proposed as a risk factor for PGD and an increased AMA titre for PPT. Depending upon clinical manifestations, severity, patient and physician preferences, PGD can be treated by one of several choices of conventional therapy. The transient thyrotoxic phase of PPT when relatively asymptomatic may require no therapy, but when symptomatic, only conservative therapy with beta-adrenergic blockers, sedatives and/or tranquilizers is indicated. Close follow-up and long-term surveillance of mothers with PH due to PPT is essential for early detection and management of a possible subsequent hypothyroid phase, which may be symptomatic, but is seldom permanent. Treatment of recurrent episodes of PPT is controversial. Thyrotoxic symptoms are usually mild and transient and can best be managed by symptomatic therapy as indicated. In a few exceptional patients with recurrent episodes, prophylactic treatment with corticosteroid may be warranted but thyroidectomy and ablative radioactive iodine therapy is seldom justified.(ABSTRACT TRUNCATED AT 400 WORDS)

Antithyroid Agents↗
PubMed1985

DNA ligase activities during hepatocarcinogenesis induced by N-2-acetylaminofluorene.

A progressive accumulation of DNA breaks has been reported to occur in nuclear DNA obtained from putative premalignant hepatic lesions induced by carcinogens. To determine if this alteration resulted from a defect in the level of, or functional activity of DNA ligases, we compared these enzymes in normal rat liver, 24-h regenerating liver, and hepatic nodules at intervals after cessation of N-2-acetylaminofluorene (AAF) treatment. Nuclear extracts of hepatocytes were separated into soluble and chromatin fractions, and multiple forms of DNA ligase activity were obtained by AcA34 gel filtration chromatography. In activities of the two largest species, DNA ligase Ia (480 kd) and DNA ligase Ib (240 kd), were present exclusively in soluble, nuclear fractions and were increased 4-fold and 2-fold, respectively, in 24-h regenerating livers. In AAF-induced nodules, these species were increased 3-fold and 1.5-fold, respectively, above those of normal rat liver, somewhat higher than predicted from the rate of cell division. In all of the test tissues, these ligase species demonstrated identical sensitivity to inhibition with 0.1 M NaCl or heating at 50 degrees C. DNA ligase II (80 kd) was found in both soluble nuclear fractions and chromatin at approximately identical levels in all tissues tested. Ligase II from all tissues also demonstrated identical responses to salt and heat. These data support the concept that DNA ligases Ia and Ib are related to DNA replication and suggest that ligase II may be a repair enzyme. The failure to detect significant alterations from expected values in the hepatic nodules and the lack of alteration in sensitivity to salt and heat indicate that the accumulation of DNA damage (presumably breaks) previously observed in carcinogen-induced altered hepatocytes is not due to an alteration in the level or the biochemical properties of DNA ligase.

2-Acetylaminofluorene↗
PubMed1985

Small peptides bound to polysomal RNA inhibit gene expression in cell-free systems, replication of stimulated lymphocytes and DNA repair in isolated chromatin.

Polysomal poly(A)+-RNA prepared from isolated calf liver polysomes by deproteinization and affinity chromatography on oligo(dT)-Sepharose at pH 6 contains low molecular weight peptides (between 600-1500 daltons) bound noncovalently. These peptides were extracted from the poly(A)+-RNA-peptides complex by precipitation of the nucleic acids with 80% (v/v) ethanol at alkaline pH (9.5) and purified on Sephadex G-25 and G-15 columns. Further fractionation was performed by silica gel chromatography and high performance liquid chromatography (h.p.l.c.). The amino acid composition of the isolated peptidic fraction was compared with similar peptides obtained from rat liver, rabbit reticulocyte and calf thymus polysomes. Effluent (ribosomal) RNA contains only negligible amount of peptides. Isolated polysomal RNA peptides were named "deprimerones" (from Latin "deprimere"), since they have a general depressing effect on gene expression in vitro (Hillar & Przyjemski, 1979). Isolated deprimerones not only inhibit DNA transcription, RNA translation in reconstituted cell-free systems, but also DNA replication by DNA polymerase beta with single- and double-stranded DNA template and synthetic deoxyribonucleotide polymers. The inhibitory effect on replication was correlated with the inhibition of [3H]-deoxyribonucleotide incorporation in isolated chromatin and in stimulated lymphocyte cell cultures. The isolated deprimerones are characterized by similar amino acid compositions in various species.

Amino Acids↗
PubMed1985

Nuclear peptides from calf liver: large scale isolation and fractionation; control of gene expression in cell-free systems, and inhibition of growth of cells in culture.

DNA and nuclear RNA fractions contain small peptides (mol. wt. 600 - 1500) attached noncovalently. A large scale isolation procedure was developed for the extraction of such peptides directly from the lysed nuclei. Further purification and fractionation was performed with the chromatography on Sephadex, silica gel and h.p.l.c. C18 reverse phase columns. H.p.l.c. fractionation yielded eleven peaks. The peptides are rich in serine, glycine, alanine and acidic amino acids. They do not contain sulphur-containing amino acids. Only occasionally tyrosine, phenylalanine, histidine, arginine, and very moderate amount of lysine are found. These peptides are active in inhibiting gene expression in cell-free systems and incorporation of labeled thymidine in L 1210 murine leukemic cell culture. Thorough and exhaustive analysis demonstrated that the isolated peptides are not degradative products of histone or nonhistone chromosomal proteins.

Amino Acids↗
PubMed1985

Central angiotensin converting enzyme blockade and salt preference in renovascular hypertensive rats.

Previous studies have shown that the spontaneously hypertensive rat (SHR) has a preference for 0.9% NaCl solution over water as a drinking fluid. This preference was decreased by chronic treatment of SHR with intracerebroventricular captopril (an angiotensin converting enzyme inhibitor). Although other strains of rats were compared to SHR, no studies, that we are aware of, have been reported in renal hypertensive rats. Wistar-Kyoto rats were sham operated or had a silver clip (i.d., 0.20 mm) placed on the left renal artery to produce renovascular hypertension. Three weeks later the rats were operated upon again to implant osmotic minipumps to deliver captopril or saline either into the right lateral brain ventricle (i.c.v.) or into the peritoneal cavity (i.p.). The rats had a choice of 0.9% NaCl or tap water during the study. Blood pressures were measured by a tail plysmographic method in the conscious rats. The rats that became hypertensive showed a marked preference for saline. Treatment with captopril i.p. (24 mumol/kg/day) stimulated preference for saline but i.c.v. treatment (24 mumol/kg/day) decreased the preference for saline despite reductions in blood pressure in both groups of renal hypertensive rats. These changes were not seen in renal hypertensive rats infused with saline. The results suggest that captopril's antihypertensive effect in this model of renal hypertension may be independent of the effects of the drug on preference to drink saline.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

Esophageal carcinoma masquerading as recurrent acute suppurative thyroiditis.

A 61-year-old woman had clinical features of acute suppurative thyroiditis that was recurrent and refractory to antibiotic therapy. The diagnosis of acute suppurative thyroiditis was established by a fine-needle aspiration biopsy procedure, yielding suppurative material from which anaerobic and aerobic bacteria grew. Subsequent investigation with a barium swallow study followed by esophagoscopy and biopsy confirmed extensive esophageal carcinoma with a fistulous tract extending into the perithyroidal region.

Carcinoma↗
PubMed1985

Multiple roles of nucleus reticularis gigantocellularis in physiologic and pharmacologic regulation of cardiovascular functions.

This communication summarizes results from our laboratory during the past few years indicating that the nucleus reticularis gigantocellularis (NRGC) in the medulla oblongata plays an active role in the physiologic and pharmacologic regulation of cardiovascular functions. Apart from directly eliciting hypotension and cardioinhibition, the NRGC also assumes a modulatory role on the baroreceptor reflexes. Some gigantocellular reticular neurons exhibit electrophysiologic properties of cardiovascular neurons (neurons that alter their discharge frequencies in response to arterial pressure fluctuations), while others manifest cardiac rhythm-related activities. Pharmacologically, this reticular nucleus may be engaged by the centrally-acting antihypertensive agent, clonidine (Catapres, Boehringer Ingelheim), to produce hypotension and bradycardia. It may also participate in the cardiovascular suppressive effects of morphine and endogenous opioid peptides.

Animals↗
PubMed1984

Effect of laser microbeam irradiation of the nucleus on the cleavage of mouse eggs in culture.

Two-cell mouse eggs were irradiated by a helium-cadmium laser on a spot of about 4 micron2 (d = 2.2 micron) in one or both nuclei either continuously or repeatedly at 0.36 erg micron-2 sec-1 and then cultured to observe cellular development. After exposing one nucleus to the microbeam to five or seven 1-sec pulses (1.80 or 2.52 ergs micron-2, respectively), about 45% developed to the 3-cell stage in 24 hr of culture. In overnight cultures of the 2-cell eggs in which both nuclei were irradiated for 9 or 20 sec continuously, 40 (9 sec) and 50% (20 sec) of the eggs remained at the 2-cell stage, while 45 (9 sec) and 25% (20 sec) developed to the 4-cell stage. Irradiating only one nucleus in a 2-cell egg by seven pulses in a spot of 4 micron2 amounting to 10 ergs reduced cleavage 45%. When both nuclei were each irradiated by a 9-sec continuous laser beam (totaling 13 ergs), about 40% of the embryos of the 2-cell stage did not divide. The effect of seven pulses on the blastomere cleavage of 2-cell mouse eggs appeared to be comparable to that of continuous 9-sec laser irradiation. Both pulse and continuous laser microirradiation methods may be developed for inactivation of the nucleus as a nonpipetting , less injurious method for enucleation of mammalian eggs.

Animals↗
PubMed1983

Correlated effects of clonidine on single-neuron activities in the gigantocellular reticular nucleus, arterial pressure and heart rate in the cat.

In chloralose-urethane anesthetized cats, intravenous administration of clonidine (10 micrograms/kg) promoted an increase in single-neuron discharges in the gigantocellular reticular nucleus that exhibited a degree and time-course parallel to the hypotension and bradycardia produced by the imidazoline compound. This observation was taken to be a positive indication that clonidine may pharmacologically activate (or disinhibit) neurons in this reticular nucleus, which in turn elicits vasodepression and cardioinhibition.

Animals↗
PubMed1983

Qualitative analysis of intracellular characteristics of spontaneous neurons in the nucleus reticularis gigantocellularis of the cat.

The intracellular characteristics of spontaneous neurons in the nucleus reticularis gigantocellularis (NRGC) of cats were evaluated. Apart from an irregular pattern of spontaneous discharge, we demonstrated that out of 895 successfully impaled NRGC neurons, 744 had a relatively low transmembrane potential of -12 to -40 mV. Many reticular neurons manifested spontaneous pre-potentials and post-spike depolarizations, from which action potentials were observed to arise. It is discussed that the spontaneous nature of NRGC neuronal discharge may be the result of continuous presynaptic bombardments because of the special anatomic and physiologic features of the reticular formation. Alternatively, the NRGC neurons may possess pacemaker-like membrane properties.

Animals↗
PubMed1983

The protective role of thiol reducing agents in the in vitro inhibition of rat liver DNA methylase by direct acting carcinogens.

The direct-acting carcinogens N-acetoxy-N-acetyl-2-aminofluorene (AcAAF), methyl nitrosourea (MNU), and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were tested for their ability to inhibit highly purified, rat liver DNA methylase in vitro. Fifty percent inhibition of DNA methylase activity was achieved with 4.3 mM AcAAF, 47 mM MNU and 2.8 mM MNNG. When the enzyme was reassayed in the presence and absence of dithiothreitol, it was shown that DNA methylase was protected by increasing amounts of the thiol reducing agent. When other thiol reducing agents were tested for their ability to protect DNA methylase from carcinogen damage, a differential protective ability was observed. Dithiothreitol, beta-mercaptoethanol, and reduced glutathione were effective in protecting DNA methylase from carcinogen inhibition, while the effect of cysteine was intermediary and the effect of ergothioneine was minimal. These results may be related to the hypomethylation of DNA observed in several cancers, suggesting that the carcinogens achieve this effect at least in part by inhibiting crucial sulfhydryl group(s) in the methylase molecule. These data also suggest that various intracellular thiols may play an important role in protecting DNA-modifying enzymes from carcinogen damage.

Acetoxyacetylaminofluorene↗