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Biomedical subjects

H H Chung

Publications and source records attributed to H H Chung.

At least 19 recordsLinked to original sources
PubMed2001

A novel class of highly potent, selective, and non-peptidic inhibitor of Ras farnesyltransferase (FTase).

Design, synthesis and structure-activity relationship of a class of aryl pyrroles as farnesyltransferase inhibitors are described. In vitro and in vivo evaluation of a panel of these inhibitors led to identification of 2 (LB42908) as a highly potent (IC(50)=0.9 nM against H-Ras and 2.4 nM against K-Ras) antitumor agent that is currently undergoing preclinical studies.

Alkyl and Aryl Transferases↗
PubMed2001

Inactivation of farnesyltransferase and geranylgeranyltransferase I by caspase-3: cleavage of the common alpha subunit during apoptosis.

Caspase plays an important role in apoptosis. We report here that farnesyltransferase/geranylgeranyltransferase (FTase/GGTase)-alpha, a common subunit of FTase (alpha/beta(FTase)) and GGTase I (alpha/beta(GGTase)), was cleaved by caspase-3 during apoptosis. FTase/GGTase-alpha (49 kDa) was cleaved to 35 kDa (p35) in the Rat-2/H-ras, W4 and Rat-1 cells treated with FTase inhibitor (LB42708), anti-Fas antibody and etoposide, respectively. This cleavage was inhibited by caspase-inhibitors (YVAD-cmk, DEVD-cho). Serial N-terminal deletions and site-directed mutagenesis showed that Asp59 of FTase/GGTase-alpha was cleaved by caspase-3. The common FTase/GGTase-alpha subunit, but not the beta subunits, of the FTase or GGTase I protein complexes purified from baculovirus-infected SF-9 cells was cleaved to be inactivated by purified caspase-3. In contrast, FTase mutant protein complex [(D(59)A)alpha/beta(FTase)] was resistant to caspase-3. Expression of either the cleavage product (60-379) or anti-sense of FTase/GGTase-alpha induced cell death in Rat-2/H-ras cells. Furthermore, expression of (D(59)A)FTase/GGTase-alpha mutant significantly desensitized cells to etoposide-induced death. Taken together, we suggest that cleavage of prenyltransferase by caspase contributes to the progression of apoptosis.

Alkyl and Aryl Transferases↗
PubMed2001

The effects of postpartum stress and social support on postpartum women's health status.

BACKGROUND: Eastern sociocultural systems differ in many ways from Western ones, and these differences influence many aspects of the postpartum period. AIM: The purpose of this study was to determine postpartum women's health status in the wider social context of the Taiwanese family after women return home from the hospital or clinic. METHOD: A longitudinal study was conducted with data collected at the first, the third, and the fifth weeks of the postpartum period. Five hundred and twenty-six postpartum women were included in the study using stratified sampling from clinics and hospitals in Kaohsiung City in the southern part of Taiwan. The Hung Postpartum Stress Scale (HPSS), Smilkstein's Social Support Scale, and the Chinese Health Questionnaire were used to obtain information about the women's postpartum stress, social support, and health status at each time point. Data were analysed with factor analysis, repeated measures MANOVA, and multiple logistic regression. RESULTS: Three factors associated with postpartum stress were identified by factor analysis: (1) maternity role attainment, (2) lack of social support, and (3) body changes. Furthermore, the level of postpartum stress at the third and the fifth postnatal weeks was higher than at the first. Social support scores at this postnatal week were the highest among the three points in time. In addition, 29%, 41% and 41% of the women at the first, third, and fifth weeks, respectively, had minor psychiatric morbidity. CONCLUSIONS: Because the postpartum women's self-reported stress is relatively low whereas the social support is relatively high, especially from the family, this confirms Pillsbury's conclusion regarding the significance of social support during the Chinese women's postpartum period. The study also showed that the three factors associated with postpartum stress were important predictors of postpartum women's health status. Future studies should compare the level of postpartum stress, social support, and women's health status in both Western and Eastern cultures.

Adult↗
PubMed2001

Relationship between the Val158Met polymorphism of catechol O-methyl transferase and breast cancer.

A case-control study was performed to assess the potential influence of catechol O-methyl transferase (COMT) genotype on the risk of breast cancer in Korean women. One hundred and sixty-three histologically confirmed incident breast cancer cases and 163 age- and menopausal status-matched control individuals with no present or previous history of cancer were selected as study subjects. COMT genetic polymorphism was determined by gel electrophoresis after NlaIII enzyme digestion of amplified DNA. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression after adjustment for known or suspected risk factors of breast cancer. Women with at least one COMT lower enzyme activity associated allele (COMT-L) were at elevated risk for breast cancer (OR = 1.7, 95% CI = 1.04-2.78) compared with those homozygous for high enzyme activity associated COMT-H alleles. Among women with low (> or = 23.1) body mass index the COMT-L allele containing genotypes posed a marginally significant increased risk of breast cancer compared to the COMT-HH genotype (OR = 1.8, 95% CI = 0.95-3.48). Women with at least one COMT-L allele who had experienced a full-term pregnancy when aged over 30 years or were nulliparous had 2.7-fold increased risk; however, this increase did not reach statistical significance (OR = 2.7, 95% CI = 0.64-11.35). Furthermore, never-drinking and never-smoking women with at least one COMT-L allele were at increased risk of breast cancer compared to those with COMT-HH genotype with ORs of 2.0 (95% CI = 1.23-3.38) and 1.7 (95% CI = 1.04-2.62), respectively. These results are consistent with studies showing that COMT genotype of lower enzyme activity might be related to increase in risk of breast cancer, and extend this finding to Korean women.

Adult↗
PubMed2001

A multidimensional assessment of insights in schizophrenic patients.

This study aims to construct a multidimensional instrument in assessing insight of schizophrenic patients and further to examine its relationships with other factors such as psychiatric symptoms, demographic characteristics, and course of illness. An instrument (the Schedule for assessment of Insight in Psychosis, SIP) with a 4-point rating scale was constructed to assess the insight of schizophrenic patients in five dimensions. One hundred schizophrenic patients were recruited for the study and all of them received a semi-structured interview using the SIP. Their demographic variables, length of illness and severity of psychotic symptoms were analyzed for insight. The reliability and validity of the SIP were satisfactory. Significant factors related to insight were psychotic symptoms, including both positive and negative symptoms. This study showed insight was affected by a multitude of factors, and it could be assessed quantitatively in various dimensions.

Hospitalization↗
PubMed2000

A broad-spectrum caspase inhibitor blocks concanavalin A-induced hepatitis in mice.

Fulminant hepatic failure (FHF) is a clinical syndrome resulting from massive death of liver cells or sudden and severe impairment of liver function. The causes of FHF are diverse and the overall mortality is very high. Recently, it became clear that apoptosis of hepatocytes is the critical cause of acute hepatic failure in FHF. It is well known that a family of cysteine proteases called caspase is one of the key mediators of the apoptotic pathway. Thus, caspases are attractive potential targets for the treatment of disorders resulting from excessive apoptosis. In this report, we examined the activity of a new caspase inhibitor, Xyz 033 mp. This nonpeptide inhibitor showed broad-spectrum caspase-inhibiting activity and protected primary rat hepatocytes from apoptotic death. In a mouse model of FHF induced by concavalin A (Con A), Xyz 033 mp suppressed elevated AST and ALT and specifically reduced IL-1 beta concentration. Also, Xyz 033 mp rescued mice from lethal experimental hepatitis induced by Con A. In addition, histological examinations indicated that Xyz 033 mp protected hepatocytes from the fatal apoptogenic effect of Con A. These results suggest that Xyz 033 mp may be a candidate therapeutic agent for FHF caused by massive apoptotic death of hepatocytes.

Animals↗
PubMed1999

Dynamic representation of eye position in the parieto-occipital sulcus.

Dynamic representation of eye position in the parieto-occipital sulcus. Area V6A, on the anterior bank of the parieto-occipital sulcus of the monkey brain, contains neurons sensitive both to visual stimulation and to the position and movement of the eyes. We examined the effects of eye position and eye movement on the activity of V6A neurons in monkeys trained to saccade to and fixate on target locations. Forty-eight percent of the neurons responded during these tasks. The responses were not caused by the visual stimulation of the fixation light because extinguishing the fixation light had no effect. Instead the neurons responded in relation to the position of the eye during fixation. Some neurons preferred a restricted range of eye positions, whereas others had more complex and distributed eye-position fields. None of these eye-related neurons responded before or during saccades. They all responded postsaccadically during fixation on the target location. However, the neurons did not simply encode the static position of the eyes. Instead most (88%) responded best after the eye saccaded into the eye-position field and responded significantly less well when the eye made a saccade that was entirely contained within the eye-position field. Furthermore, for many eye-position cells (45%), the response was greatest immediately after the eye reached the preferred position and was significantly reduced after 500 ms of fixation. Thus these neurons preferentially encoded the initial arrival of the eye into the eye-position field rather than the continued presence or the movement of the eye within the eye-position field. Area V6A therefore contains a representation of the position of the eye in the orbit, but this representation appears to be dynamic, emphasizing the arrival of the eye at a new position.

Animals↗
PubMed1998

A glycosidase antibody elicited against a chair-like transition state analog by in vitro immunization.

Antibodies were generated against the positively charged chair-like glycosidase inhibitor nojirimycin by in vitro immunization. A number of catalytic antibodies were isolated, one of which catalyzes the hydrolysis of p-nitrophenyl beta-D-glucopyranoside 3 with a rate enhancement (kcat/kuncat) of 10(5) M over the HOAC-catalyzed reaction. The antibody discriminates modifications in the pyranoside ring of substrate 3 at the C2, C4, and the anomeric positions. The pH dependence of the reaction and chemical modification studies suggest the presence of an active-site Asp or Glu residue that may function as a general acid. This study further defines those requirements necessary to generate antibodies that efficiently cleave glycosidic bonds.

1-Deoxynojirimycin↗
PubMed1998

[The effect of husband's childbirth participation on perinatal couples' psychological responses].

The purpose of this study was to examine couples' psychological responses toward husband's childbirth participation over time and to confirm the function of the curtain in the delivery room. By a quasi-experimental and prospective longitudinal study, data were collected at three points of time from 73 couples who planned to deliver their first child at one medical center in southern Taiwan. The Zung's Self-rating Anxiety scale and Zung's Self-rating Depression Scale, the Chinese Health Questionnaire, a Social Support Scale, and the Postpartum Stress Scale were used. The two-way ANOVA with repeated measures was used to compare the means of psychological responses between experimental and control groups at each point in time. The level of wife's depression was influenced by the interaction of groups and times significantly. However, the main effect of husband's childbirth participation on couples' anxiety, depression, health status, social support and the wife's postpartum stress was not found and the limitations of the study were discussed.

Anxiety↗
PubMed1997

[Correlates of couples' attitudes toward husband's childbirth participation].

The purpose of this study was to explore the couples' attitude toward husband's childbirth participation and its context. By a cross-sectional study, data were collected from 100 couples who plant to deliver at one medical center in southern Taiwan. The modified version of individual Traditionality-Modernity Scale, a Social Support Scale, Zung's Self-rating depression scale and Zung's Self-rating Anxiety Scale, and the Chinese Health Questionnaire were used. Findings indicated that 73.0% wives and 80.0% husbands showed a favorable attitude toward husband's childbirth participation. Four factors were identified to be associated with couples' favorable attitude: (1) wife's mental support; (2) welcome for newborn's coming; (3) share in the childbirth with the wife together; (4) curiosity about the labor. In contrast, four factors related to unfavorable attitude were found: (1) unhelpful for the wife; (2) folk taboo; (3) husband's psychological impact; and (4) wife's negative body image. Moreover, logistic multiple regression indicated that those wives who desired a boy or a girl and those husbands who had junior college or below education tended to anticipate husband's childbirth participation or tended to childbirth participation. In response to the social trend, it is necessary to conduct more childbirth classes and encourage husbands to be present in the delivery room in order to promote family-oriented care in our health care system.

Adult↗
PubMed1996

The effect of child-birth class on first-time fathers' psychological responses.

The purpose of this study was to examine fathers' psychological responses to labor/delivery over time and to evaluate the effect of child-birth class on the father. A quasi-experimental and exploratory study was conducted with data collected at the 36th and the 39th weeks of pregnancy, and the first day of the postpartum period. 100 married, first-time expectant fathers in both the experimental and control groups were drawn from one medical center in southern Taiwan as a convenient sample. Three two-hour sessions of childbirth class, each lasting for one day, were conducted consecutively following the first data point for the experimental group. The "Chinese Health Questionnaire" and Zung's Self-rating Anxiety and Self-rating Depression Scales were used to obtain the first-time fathers' health status, anxiety, and depression scores at each data point. The two-way ANOVA with repeated measures was used to compare the means of psychological responses between experimental and control groups at each point in time. The main effect of classes on paternal health status, anxiety, and depression of the experimental group was not found and the limitations of the study were discussed.

Analysis of Variance↗
PubMed1995

[Infection status of anisakid larvae in anchovies purchased from local fishery market near southern and eastern sea in Korea].

A survey was carried out on the larval anisakis in anchovies (Engrauris japonica) which were caught from April to June in 1993 at the southern and eastern sea in Korea. Anisakids in anchovies were morphological classified into Anisakis type I and II and Contracaecum type B and C, after fixation in 70% alcohol and clearing in lactophenol. A total of 171 larval anisakids were collected from 150 anchovies (6.9%) out of 2,180 examined. The infection rates showed no relation with length of the anchovies. The numbers of anisakids by organs of anchovies were 96 (56.1%) from the muscle, 65 (38.0%) from the omentum, 7 (4.1%) from the intestine, 2 (1.7%) from the stomach and 1 (0.6%) from the testis. Infection rates of anchovies with anisakids by localities were 5.1% at Taebyon, 8.0% at Sokcho and 9.2% at Chungmu. The larval anisakids in anchovies may infect humans who often eat raw anchovies.

Animals↗
PubMed1995

[Risk factors related to alcohol use among adolescents of fathers with alcoholism].

The purposes of this study were: 1) to investigate the risk factors related to alcohol use among adolescents of fathers with alcoholism. 2) to compare their drinking behaviors with the adolescents whose fathers were non-alcoholics. Sixty-one adolescents, including 29 males and 32 females, aged from 12 to 22 whose fathers were alcoholics formed the case group. 122 age and sex matched adolescents in a ratio of 1:2 whose fathers were non-alcoholics were recruited as the comparison group (normal/control). Data were collected by interview during home visits or by mailing questionnaires to patients. The prevalence rates of drinking, smoking and betel-nut chewing among the adolescents of fathers with alcoholism were 67.2%, 19.7%, 18%. There was no significant difference in drinking behavior between the two groups. Beer was the most popular drink in adolescents' drinking habits. The most popular motivation of drinking was the peer pressure by friends. The significant risk factors of alcohol use among the adolescents included male poor mental health status adolescents with behavioral problems and alcohol use amongst classmates or friends.

Adolescent↗
PubMed1994

Changes in the antioxidative defensive system during open heart operations in humans.

It is known that reperfusion of the ischemic myocardium may intensify damage and increase the extent of myocardial necrosis. Oxygen free radicals and their metabolites have been implicated as possible elements in myocardial ischemia-reperfusion injury. In this study in cyanotic patients undergoing open heart operation for tetralogy of Fallot, the myocardial tissue activities of catalase, superoxide dismutase, glutathione peroxidase, and lactate dehydrogenase were determined together with the tissue contents of malondialdehyde, oxidized glutathione, and total glutathione using the spectrophotometric assay method. The tissue activities of catalase, superoxide dismutase, and glutathione peroxidase increased significantly after myocardial reperfusion (p < 0.05) when compared with the tissue activities of the control group (myocardial tissue taken immediately after aortic cross-clamping). The tissue content of malondialdehyde increased significantly after reperfusion (p < 0.05), but the tissue activity of lactate dehydrogenase and the ratio of oxidized glutathione to total glutathione showed an insignificant difference after reperfusion. These data suggest that peroxidation of the cardiac lipids was triggered by the reperfusion of the hypoxic heart, but the myocardial cellular damage was not significant enough to decrease the myocardial lactate dehydrogenase and total glutathione levels. These results also suggest that oxygen free radicals may play an important role in in-vivo myocardial reperfusion stress, but endogenous self-defensive enzyme systems to protect the cell against the cytotoxic oxygen metabolites also were triggered, and the resulting myocardial cellular damage was insignificant.

Catalase↗
PubMed1993

Probing the role of loop 2 in Ras function with unnatural amino acids.

The YDPT sequence motif (residues 32-35) in loop 2 (residues 32-40) of Ha-Ras p21 protein is conserved in the Ras protein family. X-ray crystal structures have revealed significant conformational differences in this region between the GTP- and GDP-bound forms. Moreover, mutations in this region block neoplastic transformation and prevent interaction with GTPase-activating protein (GAP), suggesting that this region may contribute to the effector function of Ras. To better understand the structural features required for GAP interaction and GTPase activity, the expanded repertoire of unnatural amino acid mutagenesis has been used to investigate the roles of the key residues, Pro-34, Thr-35, and Ile-36. A Pro-34-->methanoproline mutant, in which residue 34 is locked in the trans conformation, was found to retain high levels of intrinsic and GAP-activated GTPase activity, making unlikely conformational isomerization at this position. Deletion of a single methyl group from Ile (Ile-36-->norvaline) abolished GAP activation of Ras, revealing a remarkable specificity in this protein-protein interaction. Finally, replacement of Thr-35 with diastereomeric allo-threonine led to inactivation of Ras, demonstrating the importance of the orientation of this critical residue in Ras function.

Amino Acid Sequence↗
PubMed1993

Probing the structure and mechanism of Ras protein with an expanded genetic code.

Mutations in Ras protein at positions Gly12 and Gly13 (phosphate-binding loop L1) and at positions Ala59, Gly60, and Gln61 (loop L4) are commonly associated with oncogenic activation. The structural and catalytic roles of these residues were probed with a series of unnatural amino acids that have unusual main chain conformations, hydrogen bonding abilities, and steric features. The properties of wild-type and transforming Ras proteins previously thought to be uniquely associated with the structure of a single amino acid at these positions were retained by mutants that contained a variety of unnatural amino acids. This expanded set of functional mutants provides new insight into the role of loop L4 residues in switch function and suggests that loop L1 may participate in the activation of Ras protein by effector molecules.

Amino Acid Sequence↗
PubMed1992

Biochemical and biological activity of phosphorylated and non-phosphorylated ras p21 mutants.

In contrast to all cellular ras oncogenes which carry a single activating mutation at codon 12, 13 or 61, all known retroviral ras oncogenes have two mutations at codons 12 and 59. To understand the role of the mutation at codon 59, we have constructed plasmids containing genes for Harvey ras: p21(Gly-12,Thr-59) and p21(Val-12,Thr-59). Escherichia coli expressed proteins and their respective phosphorylated (Pi) and non-phosphorylated (non-Pi) proteins were purified to 95% homogeneity by ion-exchange chromatography and gel filtration. GTPase, autophosphorylation and nucleotide exchange activities of the mutants were studied. When the mutants were microinjected into Xenopus oocytes, the non-phosphorylated forms of p21(Gly-12,Thr-59) and p21(Val-12,Thr-59) showed high activity. Surprisingly, their phosphorylated forms were inactive. These results suggest that threonine at position 59 endows the protein with transforming activity but that phosphorylation of the residue inhibits biological activity. A structural interpretation of the observation is presented.

Animals↗