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H C Liang

Publications and source records attributed to H C Liang.

At least 37 records · Page 2Linked to original sources
PubMed1998

Role of CYP2A5 and 2G1 in acetaminophen metabolism and toxicity in the olfactory mucosa of the Cyp1a2(-/-) mouse.

Acetaminophen (AP) is a widely-used analgesic agent that has been linked to human liver and kidney disease with prolonged or high-dose usage. In rodents, the target organs that are affected include liver, kidney, and the olfactory mucosa. AP toxicity requires cytochrome P450(CYP)-mediated metabolic activation, and the isozymes CYP1A2, 2E1, and 3A are known to activate AP in the human. In the present study, we determined that olfactory mucosal toxicity of AP was not different between the Cyp1a2(+/+) wild-type and the Cyp1a2(-/-) knockout mouse, whereas the hepatic toxicity of AP was significantly diminished in Cyp1a2(-/-) mice. Western blots of olfactory mucosa revealed that CYP2E1 and CYP3A levels are similar between untreated Cyp1a2(+/+) and Cyp1a2(-/-) mice. Diallyl sulfide (DAS), a known inhibitor of CYP2E1 and of CYP2A10/2A11 (the rabbit orthologue of mouse CYP2A5), completely eliminated olfactory toxicity of AP in both the Cyp1a2(-/-) and wild-type mouse olfactory mucosa. We found that heterologously expressed mouse CYP2A5 and CYP2G1 enzymes (known to be present in olfactory mucosa) form 3-hydroxyacetaminophen (3-OH-AP) and 3-(glutathion-S-yl)acetaminophen (GS-AP); CYP2A5 is considerably more active than 2G1. Addition of GSH caused increases in GS-AP proportional to decreases in 3-OH-AP, suggesting that these two metabolites arise from a common precursor or are formed by way of competing pathways. We also found that both CYP2A5 and CYP2G1 are inhibitable by DAS in vitro. These studies provide strong evidence that, in addition to CYP2E1, CYP2A5 and 2G1 are important in AP bioactivation in the mouse olfactory mucosa and that CYP1A2 appears to be of minor importance for AP olfactory toxicity.

Acetaminophen↗
PubMed1998

Prevalence of proteinuria/microalbuminuria in an elderly urban, biethnic community.

INTRODUCTION: The purpose of this study was to compare the prevalences of urinary abnormalities, notably proteinuria and microalbuminuria, in a randomly selected, biethnic population of Hispanic and nonHispanic white males and females and to determine the effects of diabetes, hypertension, and coronary heart disease on these prevalence rates. METHODS: A survey of health and health related issues was conducted on 883 volunteers, mean age 74.1 years, selected randomly from the Medicare rolls of Bernallilo County (Albuquerque), New Mexico. The sample consisted of nearly equal numbers of Hispanic and nonHispanic white males and females. A dipstick urinalysis and test for microalbuminuria was performed on a clean void, untimed urine sample as a part of a 4-hour interview/examination. RESULTS: Of the 696 participants with complete databases, 10.5% had 1+ or greater proteinuria (30 mg/dL or more) by convential urinalysis dipstick and 19.8% had microalbuminuria (50 mg/L or more) by Micral Chemstrip methodology. Participants with diabetes mellitus (Odds Ratio (OR) 2.54, Confidence Interval (CI) 1.71-3.76, p < 0.001), and/or hypertension (OR 2.09, 95% CI 1.46-3.01, p < 0.001) were more likely to have microalbuminuria than participants without either of these conditions. After adjusting for the presence of diabetes and hypertension, there was a trend toward an increased prevalence of coronary heart disease (OR 1.23, 95% CI 0.84-1.81 p = 0.28) in those with microalbuminuria, but this did not reach levels of statistical significance. CONCLUSIONS: Hispanics, even after adjusting for a higher prevalence of diabetes, and for small differences in prevalences of hypertension and coronary heart disease, had more microalbuminuria than nonHispanic whites, and males had more microalbuminuria than females.

Aged↗
PubMed1998

Prevalences of type 2 diabetes, the insulin resistance syndrome, and coronary heart disease in an elderly, biethnic population.

OBJECTIVE: To compare the prevalences of type 2 diabetes, the various cardiovascular risk factors encompassing the insulin resistance syndrome (IRS), and coronary heart disease (CHD) in elderly Hispanics compared with non-Hispanic whites. RESEARCH DESIGN AND METHODS: Elderly Hispanics (n = 414) and non-Hispanic whites (n = 469), randomly selected from the Medicare rolls of Bernalillo County (Albuquerque, NM; age > or = 65 years), underwent a home interview followed by an interview/examination by a nurse-practitioner, nurse, and nutritionist that included an evaluation of glucose tolerance. Prevalences of total and central obesity, dyslipidemia, hypertension, and microalbuminuria also were determined. History of myocardial infarction, recent angina, and/or coronary bypass graft, and electrocardiograms (ECGs) were used to document CHD. RESULTS: Elderly Hispanics had twice the prevalence of type 2 diabetes compared with non-Hispanic whites, but the prevalence of impaired glucose tolerance was not increased in Hispanics. Mean serum fasting and 2-h post-glucola insulin concentrations, fasting insulin resistance indexes, and HbA1c were higher in Hispanics. Hispanics were shorter, weighed less, and had more total body and central obesity. The higher prevalences of dyslipidemia in Hispanics could be explained by a higher prevalence of diabetes. The prevalences of hypertension and CHD were not different for the two ethnic groups. CONCLUSIONS: Elderly Hispanics had twice the prevalence of diabetes and higher prevalences of cardiovascular risk factors associated with IRS. Prevalences of hypertension and CHD were similar in the two ethnic groups.

Aged↗
PubMed1997

Sensitivity of CYP1A1 mRNA inducibility by dioxin is the same in Cyp1a2(+/+) wild-type and Cyp1a2(-/-) null mutant mice.

In mammals, the induction of experimental porphyria by halogenated aromatic hydrocarbons (HAHs) seems to be influenced by the levels of hepatic CYP1A2. The pharmacokinetics and relative rates of uptake and storage of HAHs in the liver are correlated with hepatic CYP1A2 concentrations. It is possible that these rates of HAH uptake and storage might affect the expression of other HAH-inducible genes. The differential inducibility of liver CYP1A1 mRNA by dioxin was therefore compared in Cyp1a2(+/+) wild-type mice, Cyp1a2(+/-) heterozygotes, and Cyp1a2(-/-) homozygous null mutants. Using doses of dioxin over eight orders of magnitude (from 10[-12] to 10[-4] g/kg), we could detect no differences in the sensitivity of CYP1A1 mRNA inducibility. These data indicate that the complete absence of the microsomal CYP1A2 enzyme has no measurable effect on hepatic expression of the Cyp1a1, gene, the only other known member of the mammalian CYP1A cytochrome P450 subfamily.

Animals↗
PubMed1997

Impact of HLA-H mutations on iron stores in healthy elderly men and women.

The DNA of 287 healthy white elderly volunteers in the New Mexico Aging Process Study, between 63 and 91 years of age, was examined for mutations of the HLA-H gene at nt 845 and nt 187. None were found to be homozygous for the 845A mutation and there were no gender differences in the percentage of the various mutations. The frequency of the 845A mutation was 0.061 resulting in a carrier frequency of 12.2%. The frequency of the 187G mutation was 0.136 resulting in a carrier frequency of 19.9% for a single mutation; 2.4% were compound heterozygous, 834A/187G and 2.4% were homozygous for the 187G mutation. After excluding 5 men and 4 women with microcytic or macrocytic anemia, mean percent transferrin saturation (PSAT) and iron stores, as estimated from serum ferritin concentrations, were calculated for each mutation. Estimated iron stores were normally distributed (range approximately 50 to 1,550 mg) with men (n=111) having significantly higher mean estimated iron stores than women (n=167), 826 +/- 318 and 753 +/- 287 mg, respectively. More men, 15 of 28, (54%) with estimated iron stores in the upper quartile, >/= 1,050 mg, had a HLA-H mutation compared to 25 of 83 (30%) who had a mutation and whose estimated iron stores were < ,050 mg, P<0.05. Seven were heterozygous for the 845A mutation with mean estimated iron stores of 1,300 +/- 127 mg, 7 were heterozygous for the 187G mutation with mean estimated iron stores of 1,439 mg. Similar differences were not noted in women. Even though the potential role of the 187G mutation in the phenotypic expression of HH is less certain than the 845A mutation, the increase in PSAT seen in men with the 187G mutation and the equal distribution of 845A and 187G mutations seen with iron stores >/= 1,050 mg lends support for the involvement of the 187G mutation, or a linked mutation, in iron metabolism. We concluded that men having either a single chromosomal 845A and/or 187G mutation results in higher PSAT's and estimated iron stores than if no HLA-H mutation were present.

Aged↗
PubMed1996

Cyp1a2(-/-) null mutant mice develop normally but show deficient drug metabolism.

Cytochrome P450 1A2 (CYP1A2) is a predominantly hepatic enzyme known to be important in the metabolism of numerous foreign chemicals of pharmacologic, toxicologic, and carcinogenic significance. CYP1A2 substrates include aflatoxin B1, acetaminophen, and a variety of environmental arylamines. To define better the developmental and metabolic functions of this enzyme, we developed a CYP1A2-deficient mouse line by homologous recombination in embryonic stem cells. Mice homozygous for the targeted Cyp1a2 gene, designated Cyp1a2(-/-), are completely viable and fertile; histologic examination of 15-day embryos, newborn pups, and 3-week-old mice revealed no abnormalities. No CYP1A2 mRNA was detected by Northern blot analysis. Moreover, mRNA levels of Cyp1a1, the other gene in the same subfamily, appear unaffected by loss of the Cyp1a2 gene. Because the muscle relaxant zoxazolamine is a known substrate for CYP1A2, we studied the Cyp1a2(-/-) genotype by using the zoxazolamine paralysis test: the Cyp1a2(-/-) mice exhibited dramatically lengthened paralysis times relative to the Cyp1a2(+/+) wild-type animals, and the Cyp1a2(+/-) heterozygotes showed an intermediate effect. Availability of a viable and fertile CYP1A2-deficient mouse line will provide a valuable tool for researchers wishing to define the precise role of CYP1A2 in numerous metabolic and pharmacokinetic processes.

Animals↗
PubMed1996

Vitamin supplementation and other variables affecting serum homocysteine and methylmalonic acid concentrations in elderly men and women.

OBJECTIVE: An elevated serum concentration of the metabolite, homocysteine (Hcys): 1) can indicate folate or vitamin B12 deficiency, 2) is an independent risk factor for vascular disease. The metabolite, methylmalonic acid (MMA), is elevated in deficiency of vitamin B12, but not folate. The purpose of this study was to determine the effect of self-selected vitamin supplementation and other variables on serum Hcys and MMA concentrations in elderly men and women. METHODS: Serum concentrations of Hcys, MMA, folate and vitamin B12 were measured for elderly volunteers, age 68-96 years, and compared for those consuming (26 men, 25 women) and not consuming (24 men, 25 women) self-selected vitamin supplements. RESULTS: Compared with the nonsupplemented group, the supplemented group had lower mean serum MMA (208 +/- 162 vs. 241 +/- 98 nmol/L [+/- SD]) and Hcys (9.5 +/- 2.6 vs. 11.2 +/- 2.7 mumol/L); and higher serum vitamin B12 (391 +/- 174 vs 292 +/- 107 pmol/L), and serum folate (46 +/- 15 vs. 24 +/- 10 nmol/L) p < 0.05. Among all 100 subjects, the prevalence of serum vitamin B12 < 221 pmol/L (300 pg/mL) was 18; MMA > 271 nmol/L, 16; Hcys > 16.2 mumol/L, 3; folate < 5.0 nmol/L, none. Based on serum vitamin B12 < 221 nmol/L with elevated serum MMA, vitamin B12 deficiency was probable in seven subjects, of whom two were supplemented. All three subjects with elevated serum Hcys had elevated serum MMA as well, suggesting vitamin B12 deficiency or renal insufficiency. A stepwise linear regression model for serum Hcys explained 61.7% of the variance, and included (in order) serum creatinine, folate, vitamin B12, albumin, age and body mass index (BMI). A model with serum MMA replacing serum vitamin B12 explained 64.1% of the variance in serum Hcys. Folate did not enter the model for supplemented subjects, supporting a "threshold effect": serum Hcys was inversely related to serum folate at lower serum folate (nonsupplemented subjects), but at higher serum folate (supplemented subjects), the relationship was flat. In supplemented subjects, serum Hcys was still related to vitamin B12 status, confirming that tissue deficiency of the vitamin was present. CONCLUSIONS: Results showed potential usefulness of serum MMA and Hcys in identifying subclinical or tissue deficiency of vitamin B12. Clinicians should be aware of the risk of vitamin B12 deficiency in older people and of current screening algorithms using serum metabolites. These elderly volunteers had generally good folate status; nevertheless, some subjects seemed likely to benefit from an improvement in folate status that would reduce their serum Hcys within the normal range. The role of serum creatinine in the normal range in predicting serum Hcys, a vascular disease risk factor, remains unexplained.

Aged↗
PubMed1996

Mechanism of action of p-chlorobiphenyl on the inhibition of platelet aggregation.

p-Chlorobiphenyl (1-50 microM) concentration-dependently inhibited the aggregation and release reaction of rabbit washed platelets induced by arachidonic acid and collagen, but not those induced by platelet-activating factor (PAF), U46619 and thrombin. The IC50 values of p-chlorobiphenyl on the arachidonic acid and collagen-induced platelet aggregation were 2.9 +/- 0.5 and 12.8 +/- 2.3 microM, respectively. The formation of both platelet thromboxane B2 and prostaglandin D2 caused by arachidonic acid was inhibited by p-chlorobiphenyl concentration-dependently. In myo-[3H]inositol-labeled and fura-2-loaded platelets. [3H]inositol monophosphate generation and the rise in intracellular Ca2- stimulated by arachidonic acid were inhibited by p-chlorobiphenyl. In human platelet-rich plasma, p-chlorobiphenyl and indomethacin prevented the secondary aggregation and blocked ATP release from platelets induced by adenosine 5'-diphosphate and adrenaline without affecting the primary aggregation. It is concluded that p-chlorobiphenyl may be a cyclo-oxygenase inhibitor and its antiplatelet action is mainly due to the inhibition of thromboxane formation.

Adenosine Triphosphate↗
PubMed1994

[Triamcinolone acetonide in the prevention of experimental proliferative vitreoretinopathy].

Macrophages were used to induce an experimental model of proliferative vitreoretinopathy (PVR) for the evaluation of drug efficacy of triamcinolone acetonide in the prevention of PVR. After injection of macrophages into the rabbit vitreous, 1 mg of triamcinolone and 0.1 ml saline, respectively, were also injected into the vitreous of the treated group and the control group. Afterwards, on the 28th day, retinal detachment developed in 77% of the eyes in the control group and in 13% of the eyes in the treated group (n = 30, P < 0.01). The time of triamcinolone being cleared up from the vitreous was 35-63 days (average 45.5 days). Electroretinogram and transmission electron microscopic examinations demonstrated that up to 4 mg of triamcinolone was nontoxic to the retina. The results suggest that during inflammatory stage, the use of triamcinolone effectively and safely prevent the development of PVR.

Animals↗
PubMed1993

Corticosteroids and daunomycin in the prevention of experimental proliferative vitreoretinopathy induced by macrophages.

An experimental model of proliferative vitreoretinopathy (PVR) induced by macrophages simulates a special form of wound healing process in the eye and mimics the development of PVR from its initial stage. We used this model for the evaluation of drug efficacy in the prevention of PVR. One mg triamcinolone acetonide (TA), 10 micrograms daunomycin-liposome (DL), 5 micrograms free daunomycin (FD) and 0.1 ml saline or empty liposomes (as controls) were injected into the vitreous in four groups of animals (30 or 40 rabbit eyes each) after macrophage injection. Retinal detachment developed in 77.5% of the control eyes on day 28, compared to 13.3% of the TA-treated eyes (P < 0.01), to 33.3% of the eyes treated with DL (P < 0.01), and 50% of the FD-treated eyes (P < 0.05). TA cleared up from the vitreous within 35-63 days (average 45.5 days). The half-time of FD clearance was 145.5 min. Although DL declined rapidly during the first 2 days, there was an average of 0.64 microgram/ml daunomycin in the vitreous on day 14. Transmission electron microscopy showed that FD at a dosage of over 5 micrograms or DL over 20 micrograms was toxic to the retina and that up to 4 mg TA was nontoxic. These results suggest that steroids such as TA, given at the inflammatory stage, can effectively and safely prevent the development of PVR, and that encapsulation in liposomes of cytotoxic agents such as daunomycin can enhance drug efficacy and reduce toxicity. The time course of initiation and development of PVR is important in the selection of particular drugs.

Animals↗
PubMed1992

"Oxidative stress" response in liver of an untreated newborn mouse having a 1.2-centimorgan deletion on chromosome 7.

The c14CoS/c14CoS mouse has a homozygous deletion of about 1.2 cM on chromosome 7 that includes the albino (c) locus. The untreated 14CoS/14CoS newborn has been reported to exhibit a marked transcriptional activation of the hepatic NAD(P)H:menadione oxidoreductase (Nmo-1; DT diaphorase; quinone reductase; azo dye reductase) gene, as well as elevated UDP glucuronosyl-transferase (UGT1*06) and glutathione transferase (GT1) activities, when compared with the cch/cch wild-type and the cch/c14CoS heterozygote. We show here that the newborn hepatic activities of seven enzymes that play a role in the oxidative stress response--NMO1, UGT1*06, GT1, copper-zinc superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase--are increased 1.5- to 25-fold in 14CoS/14CoS, as compared with ch/ch and ch/14CoS mice. The activities of four additional enzymes having no known association with the oxidative stress response--benzo[a]pyrene hydroxylase (CYP1A1, cytochrome P(1)450), acetanilide 4-hydroxylase (CYP1A2, cytochrome P(3)450), lactate dehydrogenase (LDH), and NADPH-cytochrome c reductase--are not significantly different among the three genotypes. These data suggest that there exists an "oxidative stress" response in the untreated 14CoS/14CoS newborn. We postulate that a chromosome 7 regulatory gene, which we have named Nmo-1n, might encode a trans-acting negative effector of the Nmo-1 gene, and genes corresponding to the other elevated enzymic activities described above. When both copies of Nmo-1n are deleted, as is the case in 14CoS/14CoS mice, a battery of genes involved in oxidative stress is released from negative control and becomes activated--despite the absence of any apparent oxidative insult by foreign chemicals.

Animals↗
PubMed1992

Induction of an organ-specific autoimmune disease, lymphocytic hypophysitis, in hamsters by recombinant rubella virus glycoprotein and prevention of disease by neonatal thymectomy.

Glycosylated, membrane-associated E1 (58-kDa) and E2 (47- to 49-kDa) rubella virus proteins and unglycosylated nucleoprotein C (33 kDa), from separately expressed vaccinia virus recombinants, were injected into golden Syrian hamsters. Rubella virus E1 and E2 glycoproteins consistently induced an organ-specific autoimmune disease, autoimmune lymphocytic hypophysitis, which was evidenced by the induction of autoantibodies against pituitary cells and by lymphocytic infiltration of the pituitary. Neonatal thymectomy prevented the disease. In contrast, rubella virus nucleoprotein C did not induce either autoantibodies against pituitary cells or lymphocytic infiltration of the pituitary. This finding raises the possibility that virus-specific protein itself can induce an organ-specific autoimmune disease in certain circumstances.

Animals↗
PubMed1992

Erythrocyte sodium-lithium countertransport in Chinese: its relationship to family history of hypertension.

Rates of sodium (Na+)-stimulated lithium (Li+) efflux (Na(+)-Li+ countertransport) and ouabain-sensitive Na+ efflux (Na+ pump) were determined in erythrocytes of Chinese normotensive and hypertensive subjects. Near-maximal rate of Na(+)-Li+ countertransport was found to be significantly higher in hypertensive than normotensive subjects. No significant difference was observed for the rate of Na+ pump between them. A second series of study involved normotensive subjects without and with hypertensive parent(s) (group A and B, respectively) and hypertensive subjects (group C). We found that the rate of Na(+)-Li+ countertransport in group A was significantly lower than that of group B and C, while no difference existed between group B and C. No significant difference was observed for the rate of Na+ pump among the three groups. Our results suggested that Na(+)-Li+ countertransport activity could be a genetic marker for essential hypertension in Chinese, similar to that as proposed in Caucasians.

Adult↗
PubMed1992

The effect of total intravenous propofol on spontaneous respiration during anesthesia for minor surgery.

To evaluate adequate anesthetic depth without unacceptable respiratory consequences during total propofol intravascular anesthesia without intubation, the respiratory response was studied in 20 healthy patients (ASA class I or II), aged 20-50, premedicated with fentanyl 2 micrograms/kg. Anesthesia was induced in all patients with propofol 2.5 mg/kg, subsequently maintained by continuous propofol infusion at 12 mg/kg/h. An additional bolus of 20-60 mg propofol was given when anesthesia was considered inadequately. Assisted ventilation with 100% oxygen through a face mask was applied when apnea time was longer than 60 s. The mask was removed when patients regained spontaneous breathing. During induction stage, 7 patients developed apnea which required ventilatory support, although the period of apnea was short. Among them four regained spontaneous breathing within 5 min, and three within 10 min. PaCO2 significantly increased at both 10 min and 20 min after induction as compared with those before induction (p less than 0.05), while the change between 10 min and 20 min after induction was not statistically different. PaO2 showed little change and also it was not statistically significant. During maintenance of anesthesia spontaneous ventilation was stable and adequate. Though mild hypercapnia was noted, no medication was necessary. There was no episode of arterial oxygen desaturation throughout the course of maintenance. All patients could be adequately anesthetized except for six patients who required additional dose for insufficient anesthetic depth. No major adverse reactions occurred during or after induction. We concluded that the respiratory effect of propofol in total intravenous anesthesia could be divided into two stages: the induction stage and the maintenance stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Erythrocyte Li-Na countertransport in hypertension: lack of atrial natriuretic peptide effect.

The rate of erythrocyte Li-Na countertransport and cellular Na+ and K+ contents have been determined in normotensive (NT) and hypertensive (HT, essential hypertension) subjects in the presence and absence of atrial natriuretic peptide (ANP). The rate of Li-Na countertransport was significantly higher in erythrocytes of HT subjects, while the Na+ and K+ contents were not different between the NT and HT groups. We found that ANP (10(-9) and 10(-7) M) had no effect on either the rate of Li-Na countertransport or the cellular Na+ and K+ contents. Since ANP does not influence erythrocyte Na pump and Na-K-Cl cotransport, our results suggest that the Na transport systems of human erythrocytes do not respond to ANP and this lack of response in Li-Na countertransport is independent of the status of hypertension. These findings are consistent with the view that the rate of Li-Na countertransport of erythrocytes may serve as a useful genetic marker for essential hypertension in Chinese. However, the erythrocyte transport systems cannot provide further differentiation utilizing ANP response for essential hypertension.

Adult↗