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Biomedical subjects

J K Lin

Publications and source records attributed to J K Lin.

At least 163 records · Page 9Linked to original sources
PubMed1991

Suppressive effect of geniposide on the hepatotoxicity and hepatic DNA binding of aflatoxin B1 in rats.

The effects of geniposide pretreatment on both hepatic aflatoxin B1 (AFB1)-DNA binding and AFB1 hepatotoxicity in rats has been examined. For these studies, male Sprague-Dawley rats were treated with AFB1 (2 mg/kg) by i.p. administration, and the different degrees of hepatic damage were revealed by the elevations of levels of serum marker enzymes such as aspartate aminotransferase (AST), alanine amino-transferase (ALT) and gamma-glutamyltranspeptidase (gamma-GT). After pretreatment of animals with geniposide (10 mg/kg) daily for 3 consecutive days, the enzyme elevations were significantly suppressed. This suggested that the geniposide possessed chemopreventive effects on the early acute hepatic damage induced by AFB1. Under these experimental conditions, consistent elevation of the activities of glutathione S-transferase (GST) and gamma-glutamylcysteine synthetase but not glutathione peroxidase (GSH-Px) and gamma-glutamyltranspeptidase were observed. Treatment of rats with geniposide significantly lowered hepatic GSH and GSSG levels, but the ratio of GSH to GSSG was not changed. Geniposide treatment also decreased AFB1-DNA adduct formation in AFB1-treated animals. From these results, we suggest that the protective effect of geniposide on AFB1 hepatotoxicity in rats might be due to the hepatic tissues' defense mechanisms that involve the enhanced GST activity for AFB1 detoxication and induction gamma-glutamylcysteine synthetase for GSH biosynthesis.

Aflatoxin B1↗
PubMed1991

Suppression of aflatoxin B1-induced hepatotoxic lesions by crocetin (a natural carotenoid).

The suppressive effects of crocetin (a natural carotenoid) on the hepatotoxic lesions induced by aflatoxin B1 (AFB1) were investigated in male Wistar rats. Rats were divided into five groups: groups I and II served as normal and solvent control respectively. Group III was given AFB1 (25 micrograms/day/rat) alone; group IV was given crocetin (0.1 mg/day/rat) alone; and group V received both AFB1 and crocetin. Rats received AFB1 and crocetin for 9 and 10 weeks respectively, and were maintained on basal diet for 35 weeks. At the end of the experiment (week 45), the incidence of liver lesions in rats of group V was significantly reduced by approximately 40% compared with group III. There were no liver lesions in rats of groups I, II and IV. A significant protective effect of crocetin on AFB1 hepatotoxicity was shown, as manifested by reduced effects on the activities of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase (P less than 0.01-0.001). From our previous results and present data, we suggest that the suppression of crocetin on AFB1 hepatotoxicity in the rats might be due to the defense mechanisms of hepatic tissues that elevated the GSH S-transferase activity and decreased the formation of hepatic AFB1-DNA adducts.

Aflatoxin B1↗
PubMed1991

Effects of crocetin on the hepatotoxicity and hepatic DNA binding of aflatoxin B1 in rats.

The effects of crocetin pretreatment on both hepatic aflatoxin B1 (AFB1)-DNA binding and AFB1 hepatotoxicity in rats has been examined. For these studies, male Wistar rats were treated with AFB1 (2 mg/kg) by i.p. administration, and the different degrees of hepatic damage were revealed by the elevations of levels of serum marker enzymes such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and gamma-glutamyltranspeptidase. After pretreatment of the animals with crocetin (2 or 6 mg/kg) daily for three consecutive days, the enzyme elevations were significantly suppressed. This suggested that the crocetin possessed chemopreventive effects on the early acute hepatic damage induced by AFB1. Under these experimental conditions, consistent elevations of hepatic glutathiones (GSH) and activities of glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) were observed. Crocetin treatment also decreased AFB1-DNA adduct formation in AFB1-treated animals. From these results, we suggest that the protective effect of crocetin on AFB1 hepatotoxicity in rats might be due to the hepatic tissues' defense mechanisms that elevated the cytosol GSH and the activities of GST and GSH-Px.

Aflatoxin B1↗
PubMed1990

Effect of ethanol on hepatotoxicity and hepatic DNA-binding of aflatoxin B1 in rats.

The hepatocarcinogen aflatoxin B1 is converted to reactive metabolites that bind covalently to cellular macromolecules. These metabolites may also react with glutathione, resulting in the formation of glutathione conjugates and detoxication of the reactive metabolite. When rats were pretreated with ethanol by gastric intubation at a dose of 100 mmol/kg, 6 hr (the time of maximal GSH depletion) before the administration of aflatoxin B1, the covalent binding of 8,9-epoxide-aflatoxin B1 to DNA in vivo was increased by 47% and the hepatotoxicity was also potentiated. However, the covalent binding was not increased by pretreatment with ethanol 18 hr (time with approximately normal GSH levels) before administration of the toxin, and no potentiation of hepatotoxicity was observed. Pretreatment with a non-toxic dose of ethanol had no effects on the activity of glutathione S-transferase and glutathione peroxidase. These results suggest that the depletion of GSH and the increased formation of DNA-adduct from the liver constitute an important mechanism for the potentiation of aflatoxin B1-induced hepatotoxicity by ethanol.

Aflatoxin B1↗
PubMed1990

Differential bleomycin susceptibility in cultured lymphocytes of fragile X patients and normal individuals.

The frequency of bleomycin-induced chromatid breaks was studied in cultured lymphocytes from ten fragile X patients and ten healthy controls. The results showed that the frequency of chromatid breaks was significantly higher among fragile X patients than among normal individuals. We suggest that the fragile X patients may be more susceptible to mutagens and carcinogens and, therefore, more prepotent to neoplastic induction.

Bleomycin↗
PubMed1990

Nitrosamines as potential environmental carcinogens in man.

Nitrosamines are ubiquitous in our environment and diet. Many nitroso compounds are carcinogenic in animals and most probably in man. Nitrosamines are formed from the reaction of nitrite with primary, secondary, or tertiary amines in an acid medium. Nitrate should be considered as a nitrosating agent because it can be converted to nitrite by microbial action. Many aliphatic and nitrogen-containing heterocyclic compounds can be nitrosated to form carcinogenic substances. The occurrence in food and in some drugs of several nitrosamines or their nitrosatable precursors is described. Several tobacco-specific nitrosamines have been considered as possible causative agents for human cancer. Nitrosamines may be implicated in the induction of certain human gastric cancers.

Animals↗
PubMed1990

Induction of ouabain-resistance mutation and cycle-dependent transformation of C3H/10T1/2 cells by N-nitroso-2-acetylaminofluorene.

Ouabain-resistance mutation and cell cycle-dependent transformation were studied concurrently in the C3H/10T1/2 cell line treated with N-nitroso-2-acetylaminofluorene (N-NO-AAF) or N-nitroso-N-2-fluorenylacetamide. N-NO-AAF is a new direct-acting mutagen that exhibits a very short half-life (34 min) in complete medium independent of cell number seeded. With 0.1-0.3 mM of N-NO-AAF, cytotoxicity was noted after exposure for 2 h, but another phase of cytotoxicity was observed between 8 and 24 h. N-NO-AAF was more toxic than its parent compound 2-AAF. Moreover, maximal mutation frequency at the Na+/K(+)-ATPase gene locus (ouar mutation) was attained within 30 or 40 min of exposure, dependent on dosage of N-NO-AAF. With 2-AAF, 2-AF and 2-nitrofluorene, however, no detectable mutants were found under the same conditions. In cell cycle-dependent transformation assays, cells were synchronized by release from confluence-induced arrest of proliferation, 2 concentrations of N-NO-AAF were added for 2 h at various intervals during the cell cycle. The results clearly revealed that cells in 2 specific time intervals were susceptible to malignant transformation, i.e., at 10 and 18 h (early S phase) after release from the block.

2-Acetylaminofluorene↗
PubMed1990

Sequential monitoring of cytogenetic damage in rat lymphocytes following in vivo exposure to aflatoxin B1 and N-nitrosophenacetin.

Rats were treated intraperitoneally with different concentrations of aflatoxin B1 (AFB1) or N-nitrosophenacetin (NP). Blood was sequentially drawn by venous puncture at 6, 24, 72, 120 h and 14 days after a single injection of AFB1 or NP. After AFB1 the frequency of SCEs and chromosome aberrations increased progressively and reached a maximum level after 24 h and then decreased with time. By 2 weeks post treatment, the SCE and chromosome aberration values were within the control range. A small but significant SCE induction was observed when rats were treated with NP, but no chromosome breakage was induced even at the highest dose (20 mg/kg). We suggest that the elimination of DNA damage by repair mechanisms and lymphocyte turnover is responsible for the reduction of SCEs and chromosome aberrations with time. This assay seems promising for sequential monitoring of cytogenetic damage in rat lymphocytes following in vivo exposure to genotoxicants.

Aflatoxin B1↗
PubMed1989

Inhibition of growth and development of the transplantable C-6 glioma cells inoculated in rats by retinoids and carotenoids.

Experimental data were provided to demonstrate the inhibitory effects of retinoids (retinal, retinoic acid, retinyl acetate and retinyl palmitate) and carotenoids (beta-carotene, lycopene and crocetin) on the growth and development of the C-6 glioma cells inoculated in rats. In the pretreatment experiments, most of these compounds could prolong the latency period of T50 (time for 50% tumor incidence). At week 7, the growth inhibition was 57-67% (P less than 0.02) with carotenoids and 40-55% (P less than 0.05) with retinoids. In the post-treatment experiments, the growth inhibition was 30-55% (P less than 0.05) with carotenoids and 21-42% (P less than 0.05) with retinoids. No significant hepatotoxic effect was observed in all treated groups as indicated by the constant levels of serum enzymes (e.g. aspartate amino-transferase, alanine amino-transferase and alkaline phosphatase) and bilirubin. The mechanisms of tumor inhibition through the enhancement of anti-tumor immunity by both carotenoids and retinoids were discussed.

Animals↗
PubMed1989

Anal manometric studies in hemorrhoids and anal fissures.

Manometric study with the use of continuous water perfusion system was performed on 50 patients with Grade III or IV hemorrhoids and for 29 patients with chronic anal fissure. Another 36 patients who had no anorectal symptoms or pathology were chosen as the control group. The maximal basal pressures for the controls, hemorrhoids, and chronic anal fissures were 71.2 +/- 24.9, 85.3 +/- 27.7, and 87.4 +/- 38.8 mmHg, respectively; the maximal contraction pressures for the controls, hemorrhoids, and fissures were 132.9 +/- 44.9, 158.8 +/- 58.0, and 162.1 +/- 64.5 mmHg, respectively; the lengths of the functional sphincter of the three groups were 3.7 +/- 0.5, 3.8 +/- 0.8, and 3.9 +/- 0.6 cm, respectively. The maximal basal pressures and maximal contraction pressures of the hemorrhoid and fissure patients were significantly greater than those of the control group (t test, P value less than 0.05); whereas the functional sphincter lengths of the three groups showed no significant difference.

Adolescent↗
PubMed1989

Anorectal abnormalities in progressive systemic sclerosis.

Seventeen patients with progressive systemic sclerosis (PSS) were evaluated with manometry for anorectal function, and an additional 36 age-matched normal subjects were collected as a control group. The study group had a significant decrement of maximum basal pressure (MBP), 42.6 +/- 27.0 mm Hg, in PSS as compared with the control group, 71.2 +/- 24.9 mm Hg (P = .0004). The difference in the functional length (FL) of the anal canal, PSS:control = 2.4 +/- 1.0 cm:3.7 +/- 0.5 cm (P = .0001); the volume of first defecating sensation, PSS:control = 66.3 +/- 35.2 ml:125.1 +/- 43.8 ml; the voluntary component, the difference between maximum squeeze pressure (MSP) and MBP, PSS:control = 116.6 +/- 73.6 mm Hg:61.8 +/- 35.9 mm Hg (P = .0087), were also found to be statistically significant. Nevertheless, the MSP and maximal tolerable capacity (Vmax) showed no difference in these two groups (MSP, PSS:control = 159.3 +/- 88.1 mm Hg:132.9 +/- 44.9 mm Hg, P = .259), (Vmax, PSS:control = 193.1 +/- 67.7 ml:230.0 +/- 60.9 ml, P = .0526). Twelve (71 percent) of 17 patients did not have rectoanal inhibitory reflex, and paradoxical contraction during rectal balloon inflation was noted in ten patients. Nine patients had different degrees of anal incontinence and abnormal anometric profiles were found in six of eight asymptomatic patients. Therefore, only two patients (12 percent) had neither symptoms nor anometric evidence of anorectal involvement in PSS. Two patients with long-standing disease received posterior anal repair for stool incontinence, the postoperative results were satisfactory both subjectively and objectively. The average MBP increased from 0 to 20 mm Hg, average FL from 0 to 1.5 cm. Patients complained less frequently about stool incontinence or soiling, and their daily life is now more comfortable. The analysis indicates that anorectal function in PSS is affected much more frequently and earlier than thought. Anorectal manometry can be used as an adjuvant in diagnosing controversial cases. Once anal incontinence occurs, posterior anal repair can achieve good results after six months of follow-up.

Adult↗
PubMed1989

The relationship between DNA damage and mutation frequency in mammalian cell lines treated with N-nitroso-N-2-fluorenylacetamide.

The induction of DNA single-strand breaks in C3H10T1/2 mouse fibroblasts and Chinese hamster ovary (CHO) cells by N-nitroso-N-2-fluorenylacetamide (N-NO-2-FAA) was demonstrated by the alkaline elution technique. Without metabolic activating system (i.e., rat liver S9 fraction), N-NO-2-FAA exhibits more direct and strong damaging effects on DNA than its parent compound, 2-FAA, at equal concentration in both cell lines. To compare the DNA-damaging potency of N-NO-2-FAA with other well-known carcinogens, such as benzo[a]pyrene, 2-nitrofluorene, and N-methyl-N'-nitrosoguanidine (MNNG), the order of potency is as follows: MNNG (5 microM) greater than N-NO-2-FAA (150 microM) greater than benzo[a]pyrene (20 microM) at equitoxic concentrations, LD37, in the same cell system. Another parallel experiment indicated that N-NO-2-FAA could disrupt the superhelicity of circular plasmid DNA (pBR 322) at a dose range of 0.1-50 mM; however, a complete conversion to form III linear DNA was found at the highest concentration (50 mM). After treatment with various concentrations of N-NO-2-FAA, ouabain resistance (ouar) was induced in C3H10T1/2 cells, while both ouar and 6-thioguanine resistance (6-TGr) were induced in CHO cells. The mutation frequency in the Na+/K+-ATPase locus in CHO cells (1.5 X 10(-6) mutants/microM) is higher than that in C3H10T1/2 cells (1.0 X 10(-6) mutants/microM). The maximal mutation frequency at the Na+/K+-ATPase gene locus was attained with 30 min of exposure in C3H10T1/2 cells, whereas the mutation frequency in CHO cells continued to increase up to 80 min of treatment. Similarly, the maximal mutation frequency at the HPRT locus also continued to increase up to 80 min of treatment. Finally, a linear plot of alkali-labile lesions versus 6-TGr mutations was obtained; but the same relationship was not observed in the case of ouar mutation.

2-Acetylaminofluorene↗
PubMed1989

Potentiation of ferrous sulphate and ascorbate on the microbial transformation of endogenous trimethylamine N-oxide to trimethylamine and dimethylamine in squid extracts.

The levels of trimethylamine N-oxide (TMAO) in the New Zealand (Nototodarus sloani) species of squid extracts were extremely high (above 9200 ppm). When the extracts were incubated for 2 days at 25 degrees C, approximately 60% TMAO was converted to trimethylamine (TMA) and dimethylamine (DMA). This conversion was very low or negligible at 4 degrees C, but was potentiated by the presence of ferrous sulphate (0.014 M) and ascorbate (0.014 M). Citrobacter freundii and Aeromonas hydrophilia were isolated from the extracts. Cultures of these two micro-organisms and of Escherichia coli were active in catalysing the conversion of TMAO to TMA and DMA either in extract or in aqueous solution. Chloramphenicol (0.416 mg/ml) completely inhibited the growth of these micro-organisms and also effectively blocked the conversion of endogenous TMAO to TMA in the extracts. The present findings suggest that gastro-intestinal flora and dietary ferrous salts and ascorbate may play important roles in the conversion of TMAO to TMA and DMA in man following the ingestion of squid and other TMAO-containing seafoods.

Animals↗
PubMed1989

Inhibitory effects of carotenoids and retinoids on the in vitro growth of rat C-6 glioma cells.

The inhibitory effects of 4 retinoids, namely, retinal (Ral), retinoic acid (RA), retinyl acetate (RAc), and retinyl palmitate (RP), and 3 carotenoid including beta-carotene (BCT), lycopene (LCP), and crocetin (CCT) on the growth and DNA synthesis of rat C-6 glioma cells were studied. All the retinoids and carotenoids caused reduction of plating efficiency and inhibition of the cellular growth. RA was the most potent inhibitor of plating efficiency, followed in decreasing order by RAc, Ral, LCP, RP, BCT, and CCT. The effects of various doses of retinoids and carotenoids on the inhibition of DNA synthesis were clearly demonstrated in the growing C-6 glioma cells, whereas negligible effects of these compounds on the RNA and protein synthesis were observed. These results suggested that retinoids or carotenoids are biologically active as anti-tumor agents against brain tumor cells in culture, while carotenoids appeared to be less active.

Animals↗
PubMed1989

Mutagenicity of dipyridyls and their methylated derivatives in Salmonella typhimurium/rat liver microsome system.

The Salmonella/microsome assay with strains TA97, TA98, TA100, TA1535, TA1537 and TA1538 was used to examine the potential mutagenicity of 5 dipyridyls, 1 tripyridyl, 3 dipyridinium diiodides and 2 pyridinium monoiodides. The widely used herbicide paraquat (1,1-dimethyl-4,4'-dipyridinium diiodide) and its precursor 4,4'-dipyridyl gave weak and marginal mutagenic activity to Salmonella typhimurium TA1535 and TA1538 in the presence of S9-mix. Significantly high mutagenicity was obtained with 2,2'-, 3,3'-, 2,3'-, and 2,4'-dipyridyls, 2,2',2"-tripyridyl, and 5 pyridinium salts under the same conditions. The positive mutagenic response of 2,2',2"-tripyridyl suggests that higher polymers of pyridine contaminating paraquat preparations might be mutagenic. The dose-response curves of 1,1-dimethyl-3,3'-dipyridinium diiodide and 1,1'-dimethyl-2,2'-dipyridinium diiodide revealed an exponential relationship between the number of induced revertants and the compound concentrations. The results suggested that the mechanism of mutation induced by these two compounds might be attributed to the chain reactions of their free-radicals with molecular oxygen.

Animals↗
PubMed1989

Penicillinase-type of beta-lactamase responsible for the ampicillin resistance in Escherichia coli NTUH 9501-1.

beta-Lactamases which hydrolyze the amide bonds of beta-lactam rings of penicillins and cephalosporins are widely distributed among microorganisms and play an important role in microbial resistance to beta-lactam antibiotics. These enzymes have been classified into penicillinase-type and cephalosporinase-type on the basis of their substrate specificity. Several clinical isolates of Escherichia coli from National Taiwan University Hospital (NTUH) were shown to be ampicillin-resistant and found to contain the penicillinase-type of beta-lactamase. Escherichia coli NTUH 9501-1 was chosen for further genetic analysis by recombinant DNA technology. DNAs from NTUH 9501-1 were isolated and digested with Pst I. The cellular DNA fragments were then joined with the vector DNA fragments derived from pHC 79 cosmid by Pst I digestion and followed by calf intestine alkaline phosphatase treatment. The recombinant cosmid DNAs were transfected and propagated in the wild type of E. coli DH 5. The transduced cells were selected on the basis of growth on LB plates containing ampicillin. The recombinant cosmid DNAs were re-isolated from the transductant cells and digested with Pst I. The cellular DNA fragments isolated by gel electrophoresis were able to transform DH 5 (amp(s)) to amp(r) cells. The results suggested that transposon-like DNA sequences coding for the ampicillinase-type of beta-lactamases were responsible for the penicillin resistance in E. coli NTUH 9501-1.

Ampicillin Resistance↗
PubMed1989

Treatment of metastatic colorectal adenocarcinoma with fluorouracil and high-dose leucovorin: a pilot study.

In Veterans General Hospital-Taipei, 25 patients with metastatic or recurrent colorectal adenocarcinoma were treated with a 5-day course of 5-FU (370 mg/M2/d) and high dose leucovorin (200mg/M2/d), repeated every 28 days until a progression of disease was evident. Twenty-one patients had evaluate tumor response. Among the 16 patients with measurable disease, three patients achieved partial response (PR), and their response durations were 2 months, 6 months and 6+ months. Five patients had stable disease (SD) for 4,4,6,7, and 10 months before its progression. Among the 5 patients with documented abdominal carcinomatosis, four remained stable without any progression for 5,6,12 and 12 months after treatment. The overall response rate was 57% (3PRS, 9SDs). Seven of the 12 responders had prior 5-FU exposure. Nine patients had progressive disease and 7 of them died within a few months after the start of treatment. The median duration of response was 6.7 months. The median survival for responders was 9.8 months, and for non-responders, 3.7 months. Performance status (PS) was a main determinant of response. Among the patients with PS = 0 (6 patients), there were 2 PRs and 4 SDs and with PS = 1 (8 patients), 1PR and 4 SDs. When PS = 2 or 3 (7 patients), only 2 SDs were noted. All the 25 patients were put into toxicity test to find in a mild to moderate, easily controlled state. There were 3 (12%) patients with grade 2-3 mucositis, 6 (24%) with grade 2 diarrhea, 13 (50%) with nausea and vomiting. Only 3 cases developed leucopenia but without thrombocytopenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗