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Biomedical subjects

K W Chung

Publications and source records attributed to K W Chung.

At least 55 records · Page 3Linked to original sources
PubMed1993

The expression of p53 antigen in primary malignant epithelial tumors of the liver: an immunohistochemical study.

We examined the expression of mutant p53 gene products in primary malignant epithelial tumors of the liver. Fourteen of 68 hepatocellular carcinomas, one of seven hepatoblastomas and one of nine intrahepatic cholangiocarcinomas showed nuclear staining for p53 proteins. None of the surrounding non-tumorous tissues expressed nuclear staining. The detection of p53 proteins in tumor cells was significantly higher in hepatocellular carcinomas of Oriental patients (31.6%) compared to non-Orientals (6.7%, p < 0.015). No significant differences were seen in p53 antigen expression between hepatitis B and non-hepatitis B associated hepatocellular carcinomas in Oriental patients. These results suggest a role for other environmental factors, such as aflatoxin, in the etiology of p53 mutation in hepatocellular carcinoma in Oriental patients.

Adenoma, Bile Duct↗
PubMed1993

Molecular typing of hepatitis C virus genome from sera and liver tissues of patients with anti-HCV positive chronic liver disease.

The authors investigated the distribution of HCV genotypes in patients with various chronic liver diseases in Korea. Study population was 70 individuals, positive for second generation anti-HCV EIA, consisting of 37 cases with sporadic non-A, non-B (NANB) chronic hepatitis (CH), 12 NANB hepatocellular carcinoma, 16 post-transfusion NANB hepatitis, 4 non-B blood donors and 1 healthy family member of a patient with sporadic CH. Molecular typing was performed by RT-nested PCR with type-specific primer sets deduced from the NS-5 region of HCV. The prevalence of type II was 75.0% and type III was 25.0% in sera. In liver tissues, type II HCV was shown in 63.0%, type III HCV in 3.7% and co-infections with type II and III HCV were observed in 18.5% of 27 samples biopsied. In the sera of patients with chronic hepatitis, typing results were relatively well correlated with those in tissues (75%), but type III could not be observed. Among 12 HCC patients, type III HCV appeared only in tissues, not in sera. These results suggest that type II HCV may be the major HCV type in Korea, and co-infections with type II and-III HCV may not be rare in chronic liver diseases with HCV.

Base Sequence↗
PubMed1991

The relationship between ovarian steroids and uterine estrogen receptors during late pregnancy.

Although a direct interdependence exists between the ovarian steroids, estrogen and progesterone, the exact role of these two hormones during pregnancy, especially late pregnancy, is not completely understood. Investigations have been conducted to determine whether the circulating levels of progesterone and estrogen or changes in the ratio of progesterone/estrogen in relation to the concentration of uterine estrogen receptors are associated with triggering parturition. Ninety-day old female rats were sacrificed at gestation days 14, 16, 18, 20 and two days post-partum. The plasma levels of estradiol and progesterone were measured by solid-phase radioimmunoassay. Uterine cytosol was subjected to a charcoal binding assay to determine the concentration of estrogen receptors. Our findings demonstrate that there is a significant (p less than 0.05) drop in both plasma progesterone and estradiol during late pregnancy. Also indicated is a significant (p less than 0.05) increase in uterine estrogen receptors throughout late pregnancy. Finally, during this period there is a direct correlation between the shift in the progesterone/estrogen ratio and the increase in the concentration of uterine estrogen receptors in late pregnancy.

Animals↗
PubMed1991

Effect of ursodeoxycholic acid on experimental hepatic porphyria induced by griseofulvin.

Griseofulvin(GF) has become the drug of choice as an antifungal agent for patients who suffer from many kinds of fungal infection. In order to clarify hepatic injury by griseofulvin(GF) overload and the effect of UDCA on GF-induced hepatic injury, the authors carried out biochemical, histologic, and ultrastructural studies of liver following treatment with griseofulvin and ursodeoxycholic acid(UDCA) in mice. Urine porphobilinogen excretion in the group treated with GF alone was significantly increased and reached the highest level in the 4th week and declined thereafter. Biochemical studies of the liver function showed no remarkable changes of serum bilirubin levels throughout the experimental period in all groups, except for SGPT and alkaline phosphatase activities which were significantly elevated and reached the highest level in the second week. Then they slightly decreased in GF treated groups(GF alone and GF plus UDCA) in comparison with the control group. Pathologic findings in the group treated with GF alone include focal liver cell necrosis(esp, zone 3), Mallory bodies in hepatocytes(esp, zone 1), Kupffer cell activation, and brown protoporphyrin pigments in the hepatocytes, bile canaliculi and interlobular bile ducts with a marked inflammatory cell infiltration in the portal tracts. Under the polarizing light microscope, bile ductular and canalicular thrombi showed a "Maltese cross" birefringence in mice treated with GF alone. There is no definite finding of fatty change in hepatocyte. Under the microscope, the liver appeared normal with an intact lobular architecture in the GF plus UDCA treated group. Electron microscopically, GF-induced changes include swelling of mitochondria, globular protoporphyrin crystals in the hepatocyte cytoplasm, markedly dilated bile cannaliculi and bile ducts and the formation of a Mallory hyaline bodies in the hepatocytes. There were no noticeable structural changes in the GF plus UDCA-treated group. Therefore the results suggest that GF causes hepatic injury, namely porphyria and cholestasis, and the treatment of UDCA may have cytoprotective and choleretic effects on GF-induced hepatic injuries.

Alanine Transaminase↗
PubMed1990

Effects of chronic ethanol intake on aromatization of androgens and concentration of estrogen and androgen receptors in rat liver.

The present study was carried out to investigate if ethanol alters aromatization of androgens and concentrations of hepatic estrogen and androgen receptors. Hepatic aromatization of androgen to estrogen was significantly increased by ethanol administration. There was a significant increase in serum estrogen level but a decreased circulating testosterone level in alcohol-fed rats. Furthermore, the concentration of estrogen receptors in liver cytosol was significantly higher in alcohol-fed rats (37 +/- 5.3 fmol/mg protein), as compared to the intact control value (21 +/- 4.8 fmol/mg protein). However, hepatic androgen receptor levels were much lower (4.4 +/- 0.5) in alcohol-fed rats than those (10.2 +/- 1.4 fmol/mg protein) in control animals. Similarly, castration increased hepatic aromatization of androgens and concentrations of serum estrogen and hepatic estrogen receptors, but it decreased contents of circulating androgen and hepatic androgen receptors. These findings indicate that alcohol administration is considered a chemical form of castration, altering the hepatic steroid metabolism and sex hormone receptor contents and contributing to the pathogenesis of feminization. A combination of alcohol-feeding and castration has no synergistic effect on the hepatic steroid receptors and aromatization, but this combination does have a more profound effect in lowering the concentration of circulating androgen.

Administration, Oral↗
PubMed1989

Effect of ethanol on androgen receptors in the anterior pituitary, hypothalamus and brain cortex in rats.

The purpose of this study was to investigate ethanol-induced changes in androgen receptor sites in the anterior pituitary, hypothalamus, and brain cortex. Young adult male King-Holtzman rats were fed for 5 months a nutritionally complete liquid diet, with ethanol or isocaloric sucrose constituting 36% of the total calories. Androgen receptor sites were measured by sucrose density gradient and charcoal assay using tritiated dihydrotestosterone (DHT). Scatchard plot analysis of the data revealed that apparent dissociation constants of DHT-receptor complex for the anterior pituitary, hypothalamus, and brain cortex from alcohol-fed animals were estimated to be 0.7 +/- 0.13, 0.6 +/- 0.16 and 0.9 +/- 0.15 nM, respectively. These values are identical to those of their isocaloric controls. The concentrations of cytosol androgen receptors of the pituitary, hypothalamus, and brain cortex from alcohol-fed rats were 8.0 +/- 1.2, 6.2 +/- 1.0 and 4.9 +/- 0.7 fmol/mg protein, respectively. This represents about a 34, 24, and 22% reduction when compared to the values of the isocaloric control animals. In contrast to control rats, neither castration nor androgen or LHRH replacement to castrated alcohol-fed rats altered an alcohol-induced reduction of androgen receptor contents. Serum LH and testosterone levels were significantly decreased in alcohol-fed rats but these hormone levels were increased by administration of LHRH or norepinephrine. Such reduction of androgen receptors, serum LH and testosterone, but enhancement of these hormone levels by treatment with neurohormone and neurotransmitter in these animals suggests that ethanol exerts an adverse effect on the hypothalamic-pituitary unit and the neurotransmitter-hypothalamic hormone relationship, resulting in impairment of the androgen-induced sexual events and a suppression of the pituitary gonadotropin secretion.

Androgens↗
PubMed1987

Effects of alcohol feeding on androgen receptors in the rat pituitary gland.

Specific binding of testosterone-1 beta, 2 beta-3H by cytosol from anterior pituitary gland of alcohol-fed, isocaloric control, and castrated control and alcohol-fed rats with or without testosterone treatment has been investigated by charcoal assay. The number of androgen binding sites was significantly reduced in alcohol-fed rats (8 +/- 1.0 fmoles/mg cytosol protein), when compared to the isocaloric control value (13.2 +/- 2.1 fmoles/mg protein), with no significant change in Kd (0.7 +/- 0.14 nM). Castration significantly increased the number of receptor sites in control rats and when castrated control animals were treated with testosterone the binding sites were decreased to the intact control level. In contrast, castration or testosterone given to castrated alcohol-fed rats did not alter alcohol-induced reduction of the receptor sites. The binding affinity (Kd) is identical in all groups. The concentration of serum luteinizing hormone (LH) was significantly lower in alcohol-fed rats when compared to that of normal controls. An increased serum LH level with a decreased testosterone level was noted in castrated control rats. However, castration of alcohol-fed rats had little or no effects on the concentrations of LH and testosterone. Administration of testosterone suppressed castration-induced high LH in control rats but alcohol-induced reduction of LH level was not altered by this treatment. These findings indicate that alcohol exerts a suppressive effect on the content of androgen receptors and secretory functions of gonadotropins in the pituitary gland.

Animals↗
PubMed1987

Absence of a 23 kd protein in testes of testicular feminization rat.

Cryptorchid testes of testicular feminization rats are very low in zinc in spite of normal zinc status of the animals. Analysis of the cytosol of the cryptorchid testes by gel permeation chromatography showed decreased zinc binding by proteins eluted at fractions corresponding to 30,000 dalton. Further analysis by sodium dodecylsulphate polyacrylamide gel electrophoresis indicated the absence of a protein with molecular weight of 23,000.

Androgen-Insensitivity Syndrome↗
PubMed1987

Safety and immunogenicity of a new heat-inactivated hepatitis B virus vaccine in adult recipients.

A new heat inactivated HBV vaccine has been evaluated for safety and immunogenicity in 203 adult recipients. The vaccine was found to be safe and highly immunogenic. Three doses of 3 micrograms given at 0, 1 and 6 months, resulted in 96% seroconversion. Three doses of 3 micrograms given at 0, 1 and 2 months produced, more rapidly, seroconversion in 92% of those immunized. Antibody to a pre-S determinant developed in four of six subjects tested.

Adult↗
PubMed1987

Independent regulatory influence of growth hormone on the hepatic synthesis of alpha 2u-globulin.

Administration of GH through sc injections to hypophysectomized male rats induces the hepatic mRNA for alpha 2u-globulin (a male-specific urinary protein) from an undetectable level to 43.4% of the normal male level. The same treatment administered to hypophysectomized-gonadectomized rats and androgen-insensitive Tfm rats induces alpha 2u-globulin mRNA to a level of only 5-10% of that in the normal male. However, none of these types of animals shows an appreciable response when GH is administered continuously through osmotic minipumps. Perfusion of the livers derived from hypophysectomized male rats with the blood from hypothyroid rabbits (also deficient in GH) was used to examine in vitro effects of GH on alpha 2u-globulin synthesis. Supplementation of the perfusion medium with GH and T4 failed to induce alpha 2u-globulin within the perfusion period of 120 min. These results show that GH can influence alpha 2u-globulin synthesis independent of the androgen and that the mode of administration of GH plays an important role in its biological response.

Alpha-Globulins↗
PubMed1986

Androgen receptors in ventral prostate glands of zinc deficient rats.

Androgen binding has been studied in the prostate cytosol of zinc deficient rats by charcoal assays. Rats were housed individually in plastic cages and maintained on a zinc deficient diet for 3 months. The cytosol fraction of prostate gland was incubated with various concentrations of tritiated methyltrienolone (3H-R1881, a synthetic androgen) alone or in the presence of 500-fold excess of radioinert R1881. Scatchard analysis of the data revealed that the number of androgen binding sites in the cytosol fraction of the zinc deficient rat prostate was 31 +/- 5.2 fmol/mg cytosol protein. This was significantly lower than that (84 +/- 11.5 fmol/mg protein) of the controls. Their dissociation constant (Kd = 1.6 +/- 0.6 nM) on the other hand was not different from that (1.7 +/- 0.7 nM) of control animals. This decrease in the concentration of cytosol receptor sites in the zinc deficient state suggests that this metal is involved in the androgen-binding process in the target cells.

Androstane-3,17-diol↗
PubMed1986

Abnormal zinc metabolism in unilateral maldescended testes of a mutant rat strain.

The status of zinc in a mutant rat strain with heritable maldescended testes was examined. In rats with unilateral maldescended testis, the ectopic testis consistently had decreased zinc content (121.0 +/- 23.0 micrograms zinc/g dry wt), while the eutopic testis had zinc content similar to that of normal rats (182.0 +/- 5.0 micrograms zinc/g dry wt). Uptake of zinc by the ectopic testis was comparable to normal. Sephadex gel chromatography showed greatly reduced zinc content of one of the endogenous zinc binding fractions with a mol wt of 30,000 of cytosol of the ectopic testis in spite of a near normal protein content. Incorporation of zinc-65 into this fraction was also shown to be greatly reduced in ectopic testis. Sodium dodecylsulphate-polyacrylamide gel electrophoresis demonstrated that a protein of 23,000 Da was greatly reduced in quantity. This 23-kDa protein in ectopic testis may play a role in reduced testicular function of the ectopic testis.

Animals↗
PubMed1984

Structural and functional abnormality of ectopic testes in rats.

Some males of a mutant strain of King-Holtzman rats exhibit an anomalous heritable defect manifested as either unilateral or bilateral ectopic testes. In the adult, these testes contain seemingly immature Sertoli and Leydig cells, seminiferous tubules greatly reduced in diameter, and exhibit arrested spermatogenesis. Thus, the affected testis is essentially sterile. An inability to produce normal amounts of testosterone and androstenedione by these gonads is probably a reflection of changes that have been effected in their Leydig cells. Thus, this study suggests that abnormal function of the Leydig and Sertoli cells and seminiferous tubule failure in these mutant animals result from the physiologically cryptorchid condition.

Animals↗
PubMed1983

Androgen receptors in the brain of neonatal normal male and androgen insensitive rats.

Androgen binding was investigated in the cytosol of brains from neonatal normal and tfm rats using sucrose gradient and charcoal assay. The neonatal normal rat brain contains androgen receptors which sediment at 8S in a sucrose gradient at low ionic strength and at 4S in the presence of 0.5M KC1. These receptors have a high affinity (Kd = 1.2 X 10(-9)M) for dihydrotestosterone (DHT), with a binding capacity of 7.3 X 10(-15) moles/mg cytosol protein. By contrast, there is very little, if any, high affinity androgen receptors in the neonatal tfm rat brain. Apparently, metabolism of testosterone does not affect androgen binding in the neonatal rat brain. The presence of these receptors and the occurrence of aromatization in the brain of neonatal rats are discussed in relation to their possible roles in sexual differentiation of the brain.

Animals↗
PubMed1983

Zinc metabolism in testicular feminization and surgical cryptorchid testes in rats.

Rats with testicular feminization (Tfm) had been reported to have a testis specific zinc deficiency. In this report it is demonstrated that this organ specific zinc deficiency was not corrected by intraperitoneal zinc administration. Normal littermates on the other hand showed a positive testicular response to zinc administration. The increased testicular zinc level in control animals returned to normal 1 week after the zinc treatment probably due to the fast turnover of this element in the testis. Not only surgically induced cryptorchidism but also surgical cryptorchidism and epididymodeferentectomy (to simulate Tfm conditions in normal adult rats) caused a drastic reduction in testicular zinc level. Unlike in Tfm rats, however, the decrease in zinc content in operated animals was not accompanied by a corresponding decrease in alkaline phosphatase activity. Zinc concentration and alkaline phosphatase activity in plasma or other organs were not affected by the surgical procedure. The testicular copper content in the operated animals was higher than that of the unoperated controls.

Alkaline Phosphatase↗
PubMed1983

Ectopic testes: a heritable mutation in the King-Holtzman rat: androgen-binding protein in testes and epididymides.

Assays of androgen-binding protein (ABP) were carried out on testes, and epididymal heads and tails. This strain of rat exhibits a heritable mutation physically manifested as unilateral or bilateral maldescended (ectopic) testes. When present, they are found immediately cranial to the external inguinal ring in the superficial connective tissue on the ventral body wall. Charcoal-extracted cytosols were preincubated with 16 nM tritiated 5 alpha-dihydrotestosterone ( [3H] DHT) for 16-20 h at 4 degrees C and ABP was separated by polyacrylamide gel electrophoresis under steady-state conditions in the presence of 2 nM [3H] DHT. The gels were transversely cut into 2.1-mm thick slices and serially counted in a liquid scintillation counter. Binding of [3H] DHT to ABP was assumed to be 1:1 and the sum dpm of the ABP-containing slices corrected for background was expressed as pmol DHT bound/mg protein. Compared to normal male siblings, cytosol ABP levels on the ectopic side in unilateral ectopic rats were 78% and 93% lower than normal in epididymal heads and tails, respectively; whereas similar values for either side in bilateral ectopic rats were 88% and 99%. The above differences indicated in the cytosol ABP levels were significant at P less than 0.0001. On the other hand, in no case were differences in ABP levels in normal and ectopic testes in bilateral ectopic, unilateral ectopic and normal male rats significant. Also, epididymal heads and tails on the descended side of unilateral ectopic rats demonstrated no significant difference when compared to corresponding tissues in normal male siblings.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen-Binding Protein↗
PubMed1982

Effect of aminoglutethimide on the structure and function of rat adrenals.

The effects of aminoglutethimide (AG) on adrenal ultrastructure, cholesterol accumulation, and steroidogenesis were studied in rats. AG was capable of altering the fine structure of the adrenocortical cells. In rats treated with this drug, adrenal mitochondria were polymorphic and their cristae were elongated and frequently showed unusual arrangement. These organelles tended to surround the lipid droplets and were often found to be gigantic in size. AG was also able to block the cholesterol side chain cleavage (CSCC) enzyme system, cause an accumulation of cholesterol in the adrenal gland, and cause decrease in serum testosterone concentration. When AG was administered along with adrenal-corticotropic hormone (ACTH), the effects were more apparent. However, there was no difference in serum testosterone concentration between animals treated with AG in the absence or presence of ACTH. ACTH can significantly increase in serum testosterone in castrated rats, suggesting that the low level of testosterone in operated animals causes a reflex rise in luteinizing hormone (LH) which interacts with ACTH to enhance the adrenal androgen secretion.

Adrenal Glands↗