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J Y Hong

Publications and source records attributed to J Y Hong.

70 records · Page 4Linked to original sources

Associative structure of differential inhibition: implications for models of conditioned inhibition.

Following A+/X- training (with A, X, and + being a light, tone, and footshock, respectively), rats received extinction of A and the training context, extinction of the training context alone, or no extinction. The inhibitory potential of X was then assessed with conditioned lick suppression in a neutral context using both summation and retardation tests. Extinction of the training context alone and extinction of A and the training context reduced the inhibitory potential of X appreciably and equally. Hence, what is traditionally called differential inhibition appears to depend not on the excitatory value of A but on the excitatory value of the training context. In conjunction with what is known about other inhibitory training procedures, these results suggest that a conditioned inhibitor is a stimulus that has been paired with little or no reinforcement in the presence of an accompanying stimulus that predicts greater reinforcement.

Animals↗

Enzyme mechanisms in the metabolism of nitrosamines.

Many nitrosamines are metabolized by cytochromes P450, one of which (P450IIE1) has received much attention because of its role in the metabolic activation of N-nitrosodimethylamine. This enzyme exists in man, rat, mouse, hamster and other animal species. It is inducible by fasting, diabetes and exposure to ethanol, acetone, isoniazid, benzene and other chemicals. P450IIE1 is responsible for the low Km form of N-nitrosodimethylamine demethylase and is the major enzyme catalysing the metabolic activation of this carcinogen. In addition, P450IIE1 is the most active P450 species known in the metabolism of N-nitrosoethylmethylamine and N-nitrosopyrrolidine. In the metabolism of N-nitrosobutylmethylamine, P450IIE1 preferentially oxidizes the methyl group over the butyl group, whereas P450IIB1 efficiently oxidizes both the methyl and butyl groups. P450IIB1 also catalyses the alpha-oxygenation of both the pentyl and methyl groups of N-nitrosopentylmethylamine, forming pentaldehyde and formaldehyde at a rate ratio of 2:1, as well as oxygenation at other carbons of the pentyl group. Many nitrosamines are effectively activated in nonhepatic target tissues. The metabolism of 4-(N-nitroso-methylamino)-1-(3-pyridyl)-1-butanone in lung and nasal microsomes is discussed.

Animals↗

Roles of pituitary hormones in the regulation of hepatic cytochrome P450IIE1 in rats and mice.

Cytochrome P450IIE1 (P450IIE1) is responsible for the metabolic activation of N-nitrosodimethylamine (NDMA), a potent environmental carcinogen. This P450 enzyme displays a high-affinity NDMA demethylase (NDMAd) activity and is known to be induced by fasting and acetone administration. In the present work, the effects of pituitary hormones on the regulation of P450IIE1 in the liver were investigated and compared in rats and mice. There was no difference in liver microsomal NDMAd activity (nmol/min/mg protein) in rats in the intact (0.38 +/- 0.12), sham-operated (0.44 +/- 0.06), and hypophysectomized (0.52 +/- 0.04) groups. However, hypophysectomy caused a 2-fold increase in hepatic P450IIE1 protein levels as determined by immunoblot analysis. The P450IIE1 mRNA level in hypophysectomized rat was also significantly increased. The levels of blood ketone bodies (acetone, acetoacetate, and beta-hydroxybutyrate) were not different in the intact, sham-operated, and hypophysectomized groups, suggesting that ketone bodies are not involved in the induction of P450IIE1 protein and its mRNA by hypophysectomy. The discrepancy between the NDMAd activity and the increased P450IIE1 protein in rat liver by hypophysectomy can be partially explained by the lower hepatic NADPH-P450 reductase activity (50% that of the control) in the hypophysectomized rats. Upon the induction of liver NDMAd activity by fasting and acetone, hypophysectomy attenuated the effect of acetone but abolished the effect of fasting completely. Nevertheless, fasting still caused a 3-fold increase in the liver P450IIE1 mRNA level. An involvement of pituitary hormones in the regulation of liver microsomal P450IIE1 in mouse, however, was not observed. There was no difference in constitutive NDMAd activity between genetically growth hormone-deficient (lit/lit) mice and their phenotypically normal heterozygotes (lit/+). Fasting for 48 h caused 1.5- to 2-fold induction and acetone caused 2- to 3-fold induction, in both groups. The above changes in enzyme activity were due to the changes of P450IIE1 levels as verified by the immunoblot analysis. In male BALB/c mice, neither the hepatic NDMAd activity nor the P450IIE1 protein level was altered by hypophysectomy. The effects of acetone on the liver NDMAd activity were also similar in hypophysectomized and sham-operated mice. The results suggest that pituitary hormones are important in the regulation of the expression and activity of hepatic P450IIE1 in rats but not in the mouse strains investigated.

Acetone↗

Roles of dietary corn oil in the regulation of cytochromes P450 and glutathione S-transferases in rat liver.

To study the molecular mechanisms by which dietary lipids affect the levels of cytochrome P450 (P450) isozymes, male Sprague-Dawley rats were fed either fat-free (FF) or 20% corn oil (CO) diet in combination with one of the following three treatments: no inducer, phenobarbital (PB) and acetone. Dietary CO did not affect the constitutive level of P450IIB (PB-inducible), but it affected the induction of P450IIB by PB treatment. The induction of P450IIB by PB in the CO group as determined by 7-pentoxy-resorufin O-dealkylase activity and immunochemically detected protein level was twofold higher than that in the FF group, and this difference was also reflected in the level of mRNA for this enzyme. In contrast, dietary CO increased the constitutive level of P450IIE (ethanol-inducible) twofold as indicated by N-nitrosodimethylamine demethylase activity and immunochemically detectable protein, but it had no effect on the induction of P450IIE by acetone. The induced level of P450IIE by acetone in the CO group did not differ from that in the FF group as measured by the enzyme activity and protein level. It was demonstrated that dietary CO affects P450IIB and IIE activities by altering the concentration of the isozymes rather than by modulating their catalytic activities. In addition, dietary CO increased the microsomal testosterone 6 beta-hydroxylase activity but not 7 alpha- and 2 alpha-hydroxylase activities, suggesting an increase in P450IIIA and/or IIC13 but not in IIA1 and IIC11, respectively. Dietary CO also affected the constitutive and induced levels of glutathione S-transferase (GST) isozymes in a different manner: it increased the constitutive level of GST-B but not that of GST-A. Nevertheless, it was important for the induction of both GST-A and GST-B by PB treatment. The results suggest that lipid nutrition affects xenobiotic metabolism activities by altering constitutive and inducible levels of certain P450 and GST isozymes.

Acetone↗

Molecular basis for the sex-related difference in renal N-nitrosodimethylamine demethylase in C3H/HeJ mice.

Previous work with rat and rabbit liver enzymes has demonstrated that cytochrome P450IIE1 is responsible for the metabolism of N-nitrosodimethylamine (NDMA), a widely occurring carcinogen. The present study demonstrated that a similar enzyme also exists in the mouse kidney and is regulated by testosterone. These results can account for the reported sex-related difference in the renal metabolism of NDMA in mouse strains such as C3H/HeJ. NDMA demethylase activities (expressed as pmol/min/mg protein) in kidney microsomes of female and male C3H/HeJ mice were 3.0 +/- 0.7 and 51.9 +/- 11.2, respectively. After testosterone treatment (500 mg/kg b.w. in olive oil, s.c.) for 2 days, the renal NDMA demethylase activity of the female mice was elevated 17-fold. The difference and change in NDMA demethylase activity were accompanied by corresponding differences and changes in P450IIE1 as quantified by immunoblot analysis (using antibodies prepared against rat P450IIE1) as well as in the mRNA level for P450IIE1 as determined by Northern and slot blot analyses (using a cDNA probe containing the coding sequence of rat P450IIE1 gene). Based on gel electrophoresis, the molecular weight of mouse renal P450IIE1 was 52,000 and the size of mouse renal P450IIE1 mRNA was approximately 1.8 kilobases; both were similar to those found in rat liver and kidney. Renal P450IIE1 mRNA levels in female, male, and testosterone-treated female mice were at a ratio of 1:22:20. On the other hand, this testosterone-related difference was not observed in hepatic P450IIE1. In liver microsomes, there were no significant differences in NDMA demethylase activity, P450IIE1 content, and P450IIE1 mRNA level between male and female mice or between untreated and testosterone-treated female mice. The apparent Km value of NDMA demethylase in mouse kidney microsomes (22 to 27 microM NDMA) were similar to that in rat liver microsomes. Renal NDMA demethylase activity was inhibited by a monoclonal antibody prepared against rat P450IIE1. These results suggest that mouse renal P450IIE1 is similar to rat P450IIE1 and is responsible for the low Km form of NDMA demethylase activity. Nevertheless, only the mouse renal enzyme is regulated by testosterone.

Animals↗

Mechanism of induction of cytochrome P-450ac (P-450j) in chemically induced and spontaneously diabetic rats.

Previous studies demonstrated that a microsomal high-affinity N-nitrosodimethylamine demethylase activity and cytochrome P-450ac (an acetone/ethanol-inducible form) were induced by streptozotocin-induced diabetes in rats. In the present work, the induction was studied in detail in two chemically induced (by streptozotocin and alloxan) diabetic rat models and one spontaneously (BB/Wor) diabetic rat model. All the diabetic conditions caused increases in three parameters: (a) microsomal N-nitrosodimethylamine demethylase activity which is known to be a good indicator of the level of P-450ac; (b) the levels of P-450ac as determined by immunoblot analysis; and (c) the levels of mRNA of P-450ac as determined by hybridization assays with a cDNA probe for this enzyme. These increases were abolished by treatment of the diabetic rats with insulin. The results suggest that the pathophysiological condition of diabetes is responsible for the induction of P-450ac and elevation of mRNA is involved in all of the three diabetic models investigated.

Animals↗

Regulation of N-nitrosodimethylamine demethylase in rat liver and kidney.

In previous work, the low Km form of N-nitrosodimethylamine (NDMA) demethylase has been demonstrated to be due to a specific form of cytochrome P-450 (designated as P-450ac) and to be the enzyme required for the metabolic activation of NDMA. The present work deals with the regulation of P-450ac in rat liver during development as well as the mechanism of induction of P-450ac in rat liver and kidney by inducers. NDMA demethylase activity was almost undetectable in the liver of newborn rats, increased after day 4, and remained elevated throughout the first 17 days of the neonatal period. The enhancement of NDMA demethylase activity during development was accompanied by corresponding increases of P-450ac content and P-450ac mRNA levels as determined by Western and slot blot analyses, respectively. No sex differences with respect to this enzyme were observed in the developing rats. Acetone treatment on late-term pregnant rats for 2 days resulted in transplacental inductions of P-450ac and P-450ac mRNA in the newborn rats. Pretreatment of young male rats and adult female rats with acetone or isopropyl alcohol caused increases of NDMA demethylase activity and P-450ac content in the liver but no significant change in the P-450ac mRNA level. These facts suggest the possible existence of a posttranscription regulatory mechanism under these induction conditions. The presence of P-450ac in rat kidney was demonstrated by Western and Northern blot analyses. The renal form of P-450ac seemed to be regulated in a fashion similar to the hepatic P-450ac regarding its response to inducing factors such as fasting and acetone treatment.

Aging↗

The induction of a specific form of cytochrome P-450 (P-450j) by fasting.

In previous work we have demonstrated that liver microsomal N-nitrosodimethylamine demethylase (NDMAd) activity is increased in rats by fasting, and we have postulated that this is due to the induction of a specific form of cytochrome P-450. This communication provides evidence for such a hypothesis. Fasting for 24 and 48 h caused 59 and 116% increases, respectively, in NDMAd activity in male rats, and fasting for 48 h caused a 63% increase in female rats. These increases were accompanied by corresponding increases of cytochrome P-450j (P-450ac) determined by immunoblotting. Fasting for 24 and 48 h also increased the mRNA for P-450j by 153 to 250%, as determined by hybridization with a cDNA probe of this cytochrome. The results suggest that fasting affects the gene expression of P-450j.

Animals↗

Pseudo-inhibitors of neutrophil superoxide production: evidence that soybean-derived polypeptides are superoxide dismutases.

We have previously reported the purification of polypeptides from soybean which are potent inhibitors of superoxide production by human neutrophils. We now report that neither oxygen uptake nor hydrogen peroxide production by stimulated neutrophils is affected by these inhibitors. Furthermore, the E-1 and E-3 polypeptides inhibit ferricytochrome c reduction by a xanthine oxidase superoxide generation system. The inhibitory activity of E-3 in the model system is blocked by 1 mM KCN while E-1 is only slightly cyanide sensitive. Atomic absorption analysis of E-1 and E-3 polypeptides reveal copper in the latter and manganese in the former. Thus, E-3 is a copper-containing superoxide dismutase while E-1 appears to be a manganese-containing superoxide dismutase.

Copper↗

A droplet medium selection for cultivation of Bacillus thuringiensis.

For an industrial fermentation system, design of a suitable medium for cultivation of cells is an important step. Medium selection is commonly carried out with a lot of experimental works. In the present study, a simple method was proposed for medium selection in cultivation of Bacillus thuringiensis for production of thuringiensin. A droplet of medium was employed to test the suitability of the medium.

Bacillus thuringiensis↗

Changing aetiologic patterns of acute viral hepatitis in Taiwanese children.

During 1981-86, 76 children were diagnosed as having acute viral hepatitis at the Department of Pediatrics, National Taiwan University Hospital, which is a major referral centre for hepatitis in children in northern Taiwan. The majority (64%) of children had acute hepatitis B which had occurred mainly during infancy. Perinatal transmission from a hepatitis B e negative surface antigen (HBsAg) carrier mother or infection through blood transfusion from a donor who had escaped notice by a less sensitive screening test (reverse passive haemagglutination test) for HBsAg were the two important modes of transmission of hepatitis B virus. The number of cases of acute hepatitis B declined after 1984, with the beginning of the nation-wide hepatitis B vaccination programme. Due to an outbreak of hepatitis A in northern Taiwan in 1982, the number of cases of hepatitis A peaked that year. Subsequently, cases of acute hepatitis A decreased remarkably. Better socio-economic conditions and improved hygiene might have contributed to the marked decrease of viral hepatitis A. The frequency of non-A, non-B hepatitis remained stable during the study period. It is possible to conclude that the aetiologic pattern of acute hepatitis in Taiwanese children changed during the past 6 years: clinical cases of hepatitis A and B decreased, probably because of more effective control of hepatitis A and B virus infections, whereas the control of non-A, non-B virus apparently requires further efforts.

Adolescent↗

Rapid diagnosis of streptococcal pharyngitis with enzyme immunoassay.

From June 1988 to May 1989, 444 throat swab specimens were tested with an enzyme immunoassay kit for rapid diagnosis of group A streptococcal pharyngitis. The results were compared with those of throat culture method. The rapid test was positive in 37 of 42 culture-positive specimens and negative in 379 of 402 culture-negative specimens, thus yielding a total agreement of 93.7%, sensitivity 88.1%, specificity 94.7%, positive predictive value 61.7%, negative predictive value 98.7%. According to this practical application, we suggest that enzyme immunoassay test can be applied in outpatient clinics by busy pediatricians for rapid diagnosis of group A streptococcal pharyngitis.

Adolescent↗

A clinical evaluation of sulbactam/ampicillin in the treatment of pediatric infections.

We have treated 42 episodes of pediatric infections with sulbactam/ampicillin since 1987. Included were 9 cellulitis, 9 urinary tract infections, 5 cervical lymphadenitis, 4 meningitis, 2 thoracic empyema, 2 osteomyelitis, 2 sepsis, 1 furuncle, 1 perianal abscess, 1 dental abscess, 1 peritonsillitis, 1 salmonellosis, 1 shigellosis, 1 peritonitis, 1 suppurative thyroiditis, 1 infective endocarditis. Responsible pathogens were Escherichia coli in 8, Staphylococcus aureus in 6, Hemophilus influenzae in 2, Streptococcus pneumoniae in 3, Streptococcus viridans in 2, Staphylococcus epidermidis in 1, Bacteroides fragilis in 1, Salmonella D1 in 1, Shigella sonnei in 1, Klebsiella pneumoniae in 1, Enterobacter agglomerans in 1, Acinetobacter calcoaceticus in 1, Enterobacter cloacae in 1, group A beta-hemolytic streptococcus in 1, and polymicrobial infection in 4 cases. Thirty-nine out of 41 (95%) clinically evaluable patients cured and all (34/34) bacteriologically evaluable patients eradicated their pathogens after treatment with sulbactam/ampicillin. Side reactions were seen in five patients; one maculopapular skin rash, one hemolytic anemia, two diarrhea, and one liver function impairment plus leukopenia. All these reactions were transient and did not require interruption of therapy. These results indicate that sulbactam/ampicillin is safe and effective in the treatment of common pediatric infections beyond the neonatal period.

Adolescent↗