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Biomedical subjects

L Liu

Publications and source records attributed to L Liu.

At least 217 records · Page 12Linked to original sources
PubMed2001

Maternal glucocorticoid treatment programs HPA regulation in adult offspring: sex-specific effects.

Pregnant guinea pigs were treated with dexamethasone (1 mg/kg) or vehicle on days 40--41, days 50--51, and days 60--61 of gestation. Adult offspring were split into two groups. Group 1 guinea pigs were catheterized, and the hypothalamo-pituitary-adrenal (HPA) axis was tested in basal and activated states. Group 2 guinea pigs were euthanized with no further manipulation. In male offspring, prenatal dexamethasone exposure resulted in a significant reduction in brain-to-body weight ratio. Dexamethasone-exposed male offspring exhibited reduced basal and activated plasma cortisol levels, which was associated with elevated hippocampal mineralocorticoid receptor (MR) mRNA and increased plasma testosterone. In females exposed to glucocorticoids in utero, basal and stimulated plasma cortisol levels were higher in the follicular and early luteal phases of the cycle, but this effect was reversed in the late luteal phase, indicating a significant interaction of sex steroids. In female offspring (at estrus), glucocorticoid receptor mRNA levels were lower in the paraventricular nucleus and pars distalis but higher in the hippocampus in animals exposed to dexamethasone in utero. Hippocampal MR mRNA levels were significantly lower (approximately 50%) than in controls. In conclusion, repeated antenatal glucocorticoid treatment programs HPA function in a sex-specific manner, and these changes are associated with modification of corticosteroid receptor expression in the adult brain and pituitary.

Aging↗
PubMed2001

Epidermal growth factor induces Egr-1 promoter activity in hepatocytes in vitro and in vivo.

Early growth response-1 (Egr-1) is a transcription factor that couples short-term changes in the extracellular milieu to long-term changes in gene expression. Under in vitro conditions, the Egr-1 gene has been shown to respond to many extracellular signals. In most cases, these findings have not been extended to the in vivo setting. The goal of the present study was to explore the role of epidermal growth factor (EGF) in mediating Egr-1 expression in hepatocytes under both in vitro and in vivo conditions. In HepG2 cells, Egr-1 protein and mRNA were upregulated in the presence of EGF. In stable transfections of HepG2 cells, a 1,200-bp Egr-1 promoter contained information for EGF response via a protein kinase C-independent, mitogen-activated protein kinase-dependent signaling pathway. A promoter region containing the two most proximal serum response elements was sufficient to transduce the EGF signal. In transgenic mice that carry the Egr-1 promoter coupled to the LacZ reporter gene, systemic delivery of EGF by intraperitoneal injection resulted in an induction of the endogenous Egr-1 gene and the Egr-1-lacZ transgene in hepatocytes. Together, these results suggest that the 1,200-bp promoter contains information for EGF response in hepatocytes both in vitro and in intact animals.

Animals↗
PubMed2001

Capsaicin inhibits activation of voltage-gated sodium currents in capsaicin-sensitive trigeminal ganglion neurons.

Capsaicin, the pungent ingredient in hot pepper, activates nociceptors to produce pain and inflammation. However, repeated exposures of capsaicin will cause desensitization to nociceptive stimuli. In cultured trigeminal ganglion (TG) neurons, we investigated mechanisms underlying capsaicin-mediated inhibition of action potentials (APs) and modulation of voltage-gated sodium channels (VGSCs). Capsaicin (1 microM) inhibited APs and VGSCs only in capsaicin-sensitive neurons. Repeated applications of capsaicin produced depolarizing potentials but failed to evoke APs. The capsaicin-induced inhibition of VGSCs was prevented by preexposing the capsaicin receptor antagonist, capsazepine (CPZ). The magnitude of the capsaicin-induced inhibition of VGSCs was dose dependent, having a K(1/2) = 0.45 microM. The magnitude of the inhibition of VGSCs was proportional to the capsaicin induced current (for -I(CAP) < 0.2 nA). Capsaicin inhibited activation of VGSCs without changing the voltage dependence of activation or markedly changing channel inactivation and use-dependent block. To explore the changes leading to this inhibition, it was found that capsaicin increased cAMP with a K(1/2) = 0.18 microM. At 1 microM capsaicin, this cAMP generation was inhibited 64% by10 microM CPZ, suggesting that activation of capsaicin receptors increased cAMP. The addition of 100 microM CPT-cAMP increased the capsaicin-activated currents but inhibited the VGSCs in both capsaicin-sensitive and -insensitive neurons. In summary, the inhibitory effects of capsaicin on VGSCs and the generation of APs are mediated by activation of capsaicin receptors. The capsaicin-induced activation of second messengers, such as cAMP, play a part in this modulation. These data distinguish two pathways by which neuronal sensitivity can be diminished by capsaicin: by modulation of the capsaicin receptor sensitivity, since the block of VGSCs is proportional to the magnitude of the capsaicin-evoked currents, and by modulation of VGSCs through second messengers elevated by capsaicin receptor activation. These mechanisms are likely to be important in understanding the analgesic effects of capsaicin.

Animals↗
PubMed2001

Control of the epidermal growth factor receptor and its ligands during renal injury.

AIM: We studied control of the epidermal growth factor (EGF) receptor and its ligands during kidney injury, since they may be importantly involved in repair. METHODS: The folic acid model of renal injury was used in these studies. Messenger RNA (mRNA) was evaluated by solution hybridization. Immunohistochemistry of transforming growth factor alpha (TGF-alpha) was also performed. RESULTS: Twenty-four hours after folic acid induced acute renal injury, creatinine increased from 0.3 +/- 0.03 mg/dl in controls to 2.0 +/- 0.8 mg/dl in folic acid injured kidneys (n = 4, p < 0.03). mRNA for the EGF receptor was increased nearly sevenfold by 24 h, and mRNA for the receptor was increased as early as 1 h following folic acid treatment. EGF receptor ligand caused a profound downregulation of the receptors in proximal tubule basolateral membranes, but receptors returned rapidly to the membrane surface in injured kidneys. The mRNA levels for heparin-binding EGF and TGF-alpha, two EGF receptor ligands, increased within 1 h of injury. TGF-alpha mRNA increased from 1.0 +/- 0.09 (relative densitometry units) in control animals to 2.9 +/- 0.13 in folic acid treated rats at 24 h (n = 4, p < 0.01), and immunohistochemical staining for TGF-alpha increased in injured kidneys at distal nephron sites. CONCLUSIONS: These studies indicate that upregulation of the EGF receptor is related to an increase in mRNA. The rapid return of receptors to the membrane surface following ligand stimulation may be useful in maintaining a mitogenic stimulus. Multiple EGF-like ligands may be important in activating the upregulated EGF receptor during repair from renal injury.

Acute Disease↗
PubMed2001

Prognostic significance of serum creatinine and uric acid in older Chinese patients with isolated systolic hypertension.

We examined the relation of serum creatinine and uric acid to mortality and cardiovascular disease in older (aged >/=60 years) Chinese patients with isolated systolic hypertension (systolic/diastolic blood pressure >/=160/<95 mm Hg). We used Cox regression to correlate outcome with baseline serum creatinine and uric acid measured in 1880 and 1873, respectively, of the 2394 patients enrolled in the placebo-controlled Systolic Hypertension in China (Syst-China) TRIAL: Median follow-up was 3 years. In multiple Cox regression analysis with adjustment for gender, age, active treatment, and other significant covariates, serum creatinine was significantly associated with a worse prognosis. The relative hazard rates (95% CIs) associated with a 20-micromol/L increase in serum creatinine for all-cause, cardiovascular, and stroke mortality were 1.16 (1.05 to 1.27, P=0.003), 1.15 (1.01 to 1.31, P=0.03), and 1.37 (1.13 to 1.65, P=0.001), respectively. In a similar analysis, which also accounted for serum creatinine, serum uric acid was also significantly and independently associated with excess mortality of cardiovascular disease and stroke. The relative hazard rates associated with a 50-micromol/L increase of serum uric acid were 1.14 (1.02 to 1.27, P=0.02) for cardiovascular mortality and 1.34 (1.14 to 1.57, P<0.001) for fatal stroke. In conclusion, in older Chinese patients with isolated systolic hypertension, serum creatinine and serum uric acid were predictors of mortality.

Age Factors↗
PubMed2001

Changes in stroke mortality rates for 1950 to 1997: a great slowdown of decline trend in Japan.

BACKGROUND AND PURPOSE: Stroke is the second leading cause of death in Japan. We sought to examine changes in stroke mortality rates by age, sex, and birth cohorts from 1950 to 1997. METHODS: The numbers of deaths from stroke and the population by age and sex in subjects aged 55 to 79 years between 1950 and 1997 were obtained from national vital statistics. Poisson regression analyses for annual percentage changes were used to explore these trends. RESULTS: Stroke mortality rates decreased since the mid-1960s for both men and women. Four periods of the decline are identified. In the first period (1950 to 1964), the age-adjusted annual percent changes averaged 0.9% for men (P<0.05) and -0.6% for women (P>0.05). In the second period (1965 to 1974), the annual change averaged -5.0% for men and -5.2% for women (both P<0.01). In the third period (1975 to 1989), the annual change averaged -8.6% for men and -8.7% for women (both P<0.01). In the fourth period (1990 to 1997), the annual change averaged -1.2% for men (P>0.05) and -3.0% for women (P<0.01). In the fourth period, the slowdown of the decline in stroke mortality was most evident in the older age groups of men. CONCLUSIONS: The findings suggested that along with an increasing aging population, the slowdown in the decline of stroke mortality rates, especially for men, is of considerable concern. Efforts to control stroke should be vigorously continued in the 2000s.

Age Distribution↗
PubMed2001

Increased cholesterol efflux in apolipoprotein AI (ApoAI)-producing macrophages as a mechanism for reduced atherosclerosis in ApoAI((-/-)) mice.

The concentration of apolipoprotein (apo) AI in the artery wall is thought to enhance cellular cholesterol efflux and protect against atherosclerosis. It has been shown that although macrophages do not make apoAI, they respond to it by increased cholesterol efflux. We hypothesized that macrophage production of apoAI would increase cholesterol efflux and reduce atherogenesis. In this study, we produced mice expressing human apoAI under the control of the macrophage-specific scavenger receptor-A promoter (mphi-AI). Human apoAI was detectable in the serum HDL fraction of mphi-AI transgenic mice at concentrations too low to affect serum cholesterol or HDL levels. Immunoblotting showed the presence of human apoAI in transgenic macrophage culture supernatants, mostly as lipoprotein-free protein, with a small component associated with HDL-like particles. Atherosclerosis studies using apoAI((-/-)) mice transplanted with mphi-AI bone marrow showed that in the absence of macrophage-derived apoE, local expression of apoAI reduced diet-induced lesions in the proximal aorta. Additionally, mphi-AI macrophages showed a 40% increase in cholesterol efflux compared with control macrophages. These data support the hypothesis that apoAI production by macrophages in the artery wall is protective against atherosclerosis. This protection is likely mediated by increased cholesterol efflux and decreased foam cell formation in vivo.

Animals↗
PubMed2001

Central melanocortin receptors regulate insulin action.

Energy balance and insulin action are tightly coregulated. Leptin regulates energy intake and expenditure partly by modulation of the melanocortin pathway in the hypothalamus. Here we demonstrate potent effects of the melanocortin pathway on insulin action and body distribution of adiposity. Conscious rats received week-long infusions of either a melanocortin receptor agonist, alpha-melanocyte-stimulating hormone (alpha-MSH), or antagonist, SHU9119, in the third cerebral ventricle while food intake was maintained constant in each group. alpha-MSH decreased intra-abdominal fat and markedly enhanced the actions of insulin on both glucose uptake and production, while SHU9119 exerted opposite effects. Our findings elucidate a neuroendocrine network that is likely to play a central role in the coupling of energy intake and insulin action.

Animals↗
PubMed2001

Interactions between simvastatin and troglitazone or pioglitazone in healthy subjects.

Two randomized, two-period crossover studies were conducted to evaluate the effects of repeat oral dosing of troglitazone (Study I) and pioglitazone (Study II) on the pharmacokinetics of plasma HMG-CoA reductase inhibitors following multiple oral doses of simvastatin and of simvastatin on the plasma pharmacokinetics of troglitazone (Study I) in healthy subjects. In both studies, each subject received two treatments. Treatment A consisted of once-daily oral doses of troglitazone 400 mg (Study I) or pioglitazone 45 mg (Study II) for 24 days with coadministration of once-daily doses of simvastatin 40 mg (Study I) or 80 mg (Study II) on Days 15 through 24. Treatment B consisted of once-daily oral doses of simvastatin 40 mg (Study I) or 80 mg (Study II) for 10 days. In Study I, the area under the plasma concentration-time profiles (AUC) and maximum plasma concentrations (Cmax) of HMG-CoA reductase inhibitors in subjects who received both troglitazone and simvastatin were decreased modestly (by approximately 30% for Cmax and approximately 40% for AUC), but time to reach Cmax (tmax) did not change, as compared with those who received simvastatin alone. Simvastatin, administered orally as a 40 mg tablet daily for 10 days, did not affect the AUC or tmax (p > 0.5) but caused a small but clinically insignificant increase (approximately 25%) in Cmax for troglitazone. In Study II, pioglitazone, at the highest approved dose for clinical use, did not significantly alter any of the pharmacokinetic parameters (AUC, Cmax, and tmax) of simvastatin HMG-CoA reductase inhibitory activity. For all treatment regimens, side effects were mild and transient, suggesting that coadministration of simvastatin with either troglitazone or pioglitazone was well tolerated. The modest effect of troglitazone on simvastatin pharmacokinetics is in agreement with the suggestion that troglitazone is an inducer of CYP3A. The insignificant effect of simvastatin on troglitazone pharmacokinetics is consistent with the conclusion that simvastatin is not a significant inhibitor for drug-metabolizing enzymes. The lack of pharmacokinetic effect of pioglitazone on simvastatin supports the expectation that this combination may be used safely.

Administration, Oral↗
PubMed2001

Polymorphic forms of expressed bovine interferon-tau genes: relative transcript abundance during early placental development, promoter sequences of genes and biological activity of protein products.

Multiple interferon (IFN)-tau genes exist in cattle, but it has remained unclear how many are expressed, the extent of their variation, and whether different genes exhibit similar patterns of expression and code for proteins with similar biological activities. A total of 118 complementary DNA (cDNA) were bi-directionally sequenced from reverse-transcribed bovine (bo) conceptus RNA over the period from blastocyst formation until day 25 of pregnancy. Fourteen different cDNAs, encoding eight different IFN-tau, were confirmed unique. All showed high sequence conservation (>98% nucleotide identity; >96% amino acid identity). The cDNA fell into three, recently evolved, phylogenetic groups (tau1, 2, and 3). Mean concentrations of IFN-tau messenger RNA were greater at day 17 and day 19 than at day 14 and day 25, with different genes showing comparable expression patterns, although there appeared to be a major bias in expression of two genes (for boIFN-tau1c and tau3a) in blastocysts. Genes representing members of the three boIFN-tau groups were cloned. Their promoter regions were conserved over regions considered important for transcriptional activation. Recombinant protein generated in Escherichia coli from representative genes in the three groups had similar but not identical antiviral activities. In summary, many IFN-tau genes, which are probably under similar transcriptional control, are expressed in bovine trophoblast during the peri-implantation period of development.

Amino Acid Sequence↗
PubMed2001

Leisure-time physical activity and other factors in relation to blood pressure in Japanese-Americans in Hawaii, USA.

To examine physical activity at work and during leisure-time as well as other factors related to blood pressure (BP) in Japanese-Americans living in Hilo, Hawaii, USA, we performed a population-based cross-sectional study with a sample of 238 participants aged 42-64 years old. This survey was carried out between 19 February and 1 March 2000 in Hilo. All participants were invited to Hilo Medical Center for a free physical examination and experimental tests including an examination of blood and urine samples. A self-administered health questionnaire was used that included items related to demographics, smoking, alcohol consumption, and habitual physical activity at work and during leisure-time. A summary score of physical activity (PA) was calculated. BP was measured using an automated BP measurement system (Khi machine, VINE Co., Ltd., Kyoto, Japan). The results showed the following. 1) Mean (SD) PA scores at work (WPA) and during leisure-time (LTPA) were 2.9 (0.5) and 2.5 (0.5) in men, and 3.0 (0.5) and 2.4 (0.3) in women, respectively; 2) Pearson correlation analyses (adjustment for age) indicated that WPA and LTPA in men show significant negative associations with SBP and DBP (p<0.05 and p<0.01), while LTPA shows significant negative associations with SBP and DBP in women (p<0.05 and p<0.01). After further adjustment for education, occupation, smoking, and alcohol consumption status, LTPA continued to show significant and negative associations with both SBP and DBP in men (p<0.01) and with DBP alone in women (p <0.01). 3) Hypertensive subjects had significantly lower mean LTPA scores than normotensive men (2.39 vs. 2.61, p<0.05) and women (2.32 vs. 2.45, p<0.05). 4) Body mass index and the ratio of sodium to potassium excretion showed significant and positive associations with SBP and DBP in multiple linear regression analyses. In conclusion, the results further emphasize that the health benefits of LTPA, control of body weight, and reduction in salt intake should continually receive strong attention in population-based high BP control.

Adult↗
PubMed2001

Ethnic and environmental differences in various markers of dietary intake and blood pressure among Chinese Han and three other minority peoples of China: results from the WHO Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study.

Our aim was to examine differences in dietary intake and blood pressure (BP) and their associations in four different ethnic Chinese populations, the Han, the Uygur, the Kazak and Tibetan subjects. This study used a sub-database of the Chinese sample of the WHO-Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. The WHO-CARDIAC Study was a multicenter cross-sectional study. In each center, 100 men and 100 women aged 48-56 years were selected at random from the local population. Various markers of dietary intake and their relation with BP were studied. The results of the present study indicated the following. 1) There were significant differences in mean BP and prevalence rates of hypertension, with both being higher in the Kazak and Tibetan subjects than in Han and Uygur subjects. 2) The highest mean body mass index (BMI) was observed in the Kazak subjects, while the highest 24-h urinary sodium (Na) and sodium to potassium (Na/K) ratio excretion were observed in the Tibetan subjects. There were also significant differences in other factors, such as magnesium, 3-methylhistidine (3MH) (a biological marker of animal protein intake) and taurine (a biological marker of seafood intake) excretion levels among the four ethnic peoples. 3) In general, BMI, Na and/or Na/K ratios were positively, and 3MH/creatinine and taurine/creatinine ratios were negatively associated with BP. 4) After adjustment for age, sex and potassium, subjects with obesity (BMI > or =26 kg/m2) had significantly higher relative risk of being hypertensive (HT) than those with BMI<26 kg/m2 in the Han, Uygur and Kazak populations; and subjects with elevated sodium excretion (Na > or =244 mmol/day) had significantly higher relative risk of being HT than those with Na<244 mmol/day in the Han, Uygur and Tibetan populations. In conclusion, mean BP and prevalence rates of hypertension were significantly different among the four ethnic groups. These differences are likely to be due, at least in part, to the differences in several diet-related factors, which in turn are associated with culture and environmental differences. Different health promotion strategies might thus be emphasized in different populations.

Blood Pressure↗
PubMed2001

Distribution of twenty-four hour urinary taurine excretion and association with ischemic heart disease mortality in 24 populations of 16 countries: results from the WHO-CARDIAC study.

There is considerable interest in the association between taurine (2-aminoethanesufonic acid) and risk of ischemic heart disease (IHD), but little information has been made available on the distribution of taurine in populations around the world. The present study aimed to describe the differences in taurine excretion levels and their associations with IHD mortality rates in 24 populations in 16 countries worldwide. This was a multicenter cross-sectional study. In each center, 100 men and 100 women aged 48-56 years were selected randomly from the local populations. Twenty-four hour urinary taurine excretion was measured using an amino acid analyzer (Hitachi 835, Ibaragi, Japan). Age-adjusted IHD mortality rates in the relevant populations were calculated using the direct standard method. The results indicated that (a) percentiles 25%, 50% and 75% of the distributions of 24-h taurine excretion showed large variations in the study populations. Median values of taurine ranged from 191.6 micromol/day (St John, Canada) to 2,180.6 micromol/day (Beppu, Japan) in males, and from 127.5 micromol/day (Moscow, Russia) to 1,590.0 micromol/day (Beppu, Japan) in females. The highest overall median value of taurine was found in the Japanese population samples, followed by the Chinese samples (Shanghai and Taiwan). European, North American and oceanic Caucasians, however, had much lower median values of taurine, except in the cases of the samples from France and Spain. (b) Median values of taurine were significantly associated negatively with age-adjusted IHD mortality rates across the 24 study population samples in men (R2=0.42, p<0.01), and in women (R2=0.55, p<0.01). These negative associations remained significant after adjustment for serum total cholesterol, body mass index and urinary sodium to potassium ratios. In conclusion, the study provides, for the first time, a cross-sectional database on distribution of 24-h urinary taurine excretion in 24 population samples worldwide. A strong and inverse association between population levels of taurine excretion and IHD mortality was observed.

Circadian Rhythm↗
PubMed2001

Number of phase levels in a two-dimensional separable Talbot array illuminator.

The number of phase levels in a Talbot array illuminator (TAIL) is an important factor for estimation of practical fabrication complexity and cost. We show that the number of phase levels in a two-dimensional TAIL (2D-TAIL) has a simple relation to the prime number. When the output array is alternatively pi phase modulated, there are similar simple relations. These simple relations should be highly interesting for practical use. An experiment with the 2D-TAIL based on the joint-Talbot effect is given as well.

Journal Article↗
PubMed2001

Molecular characterization of DDX26, a human DEAD-box RNA helicase, located on chromosome 7p12.

DEAD-box proteins comprise a family of ATP-dependent RNA helicases involved in several aspects of RNA metabolism. Here we report the characterization of the human DEAD-box RNA helicase DDX26. The gene is composed of 14 exons distributed over an extension of 8,123 bp of genomic sequence and encodes a transcript of 1.8 kb that is expressed in all tissues evaluated. The predicted amino acid sequence shows a high similarity to a yeast DEAD-box RNA helicase (Dbp9b) involved in ribosome biogenesis. The new helicase maps to 7p12, a region of frequent chromosome amplifications in glioblastomas involving the epidermal growth factor receptor (EGFR) gene. Nevertheless, co-amplification of DDX26 with EGFR was not detected in nine tumors analyzed.

Amino Acid Sequence↗
PubMed2001

Nephrin is an important component of the barrier system in the testis.

Nephrin, a gene product of the congenital nephrotic syndrome of the Finnish type (NPHS1), is a 1242-residue putative transmembrane protein of the immunoglobulin family of cell adhesion molecules. The expression of this gene is localized in rat and human glomerular epithelial cells. Here we report the expression of nephrin in various tissues other than the kidneys in mice. The expression of nephrin mRNA in various tissues of mice, including the kidneys, testes, spleen, thymus and brain, were first investigated by the RT-PCR method, and it was shown that a high level of nephrin mRNA could be detected in the testes of mice 1-6 weeks old. In situ hybridization revealed the expression of the nephrin gene in the Sertoli cells. Additionally, immunofluorescent staining studies indicated that nephrin was colocalized with anchoring protein ZO-1 in the mouse testis. From these results, it is inferred that nephrin is an important component of the barrier system in testes.

Animals↗
PubMed2001

Blood pressure and urinary cations in a low-fat intake Chinese population sample.

BACKGROUND: The relationship between cation intake and blood pressure (BP) in populations with specific dietary habits such as a low fat intake, remains unclear. A low fat intake has been prevalent during human evolution. METHODS: The average of 6 BP readings and heart rate (HR) recordings has been calculated. Dietary intake was measured using the 24 h recall-method. A 24 h urine sample was collected. RESULTS: A highly significant correlation was found between the sodium/potassium ratio (Na/K), after adjustment for age, weight, height, heart rate, alcohol intake and sex and systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP). The same applies to the sodium/creatinine (Na/Cr) and potassium/creatinine (K/Cr) ratios, with a positive correlation for Na/Cr and a negative one for K/Cr. The partial regression coefficient was in absolute value about 4-5 times greater for K/Cr than for Na/Cr. Age correlates highly significantly and independently with both SBP and DBP. CONCLUSION: If a Na/K ratio of 1 is considered optimal, by achieving that goal mean SBP could be reduced by about 6 mm Hg and mean DBP by 3 mm Hg in this normotensive population.

Adolescent↗