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Biomedical subjects

L Liu

Publications and source records attributed to L Liu.

At least 415 records · Page 23Linked to original sources

Telerehabilitation at the University of Alberta.

We established a telerehabilitation system to link staff at the University of Alberta with clinicians and students located in Two Hills, a rural community approximately 180 km east of Edmonton. From February 1996 to March 1999, the faculty of Rehabilitation Medicine conducted a total of 254 telehealth sessions, most of which involved participants in the rehabilitation discipline. Of these connections, only 11 were unsuccessful owing to technical or telecommunication problems (i.e. 96% were successful). The average duration of a session was 1 h 15 min. There were benefits to the Faculty in the areas of clinical supervision of students, clinical consultation, undergraduate and graduate education as well as professional development. The future benefits of such an initiative will depend on how well we address challenges pertaining to training, human resource and infrastructure.

Alberta↗

Twenty-four hour urinary sodium and 3-methylhistidine excretion in relation to blood pressure in Chinese: results from the China-Japan cooperative research for the WHO-CARDIAC Study.

We examined the associations between sodium and blood pressure (BP), and between 3-methylhistidine (3MH) (a marker of animal protein intake) and BP in four Chinese population samples (Guiyang, Guangzhou, Shanghai and Shijiazhuang). This work was a constituent part of the World Health Organization (WHO) Cardiovascular Disease and Alimentary Comparison (CARDIAC) Study. Each population sample consisted of 100 men and 100 women aged 48-56 yr and randomly selected using a cross-sectional study design. Twenty-four hour urine samples were collected. Urinary sodium and potassium excretion levels were measured by the flame photometry method, and 3MH was measured using a Hitachi Amino Acid Analyzer 835 (Hitachi, Ibaraki, Japan). After excluding subjects who did not complete the 24-h urine collection (as assessed by urinary creatinine excretion in relation to weight), the total study group included 314 men and 355 women. The results showed that (1) Sodium was positively, and 3MH negatively associated with systolic and diastolic BP (SBP, DBP) in both the total sample and in those who were not administered anti-hypertensive drugs; these associations were all significant (p< 0.05), and remained so after adjustment for age, sex, body mass index [BMI, weight (kg)/height (m2)], alcohol intake and potassium excretion. Sodium and 3MH were also observed to exert a combined effect on BPs. In general, subjects who had higher sodium and lower 3MH levels had higher mean SBP and DBP. This combined effect was particularly clear on SBP. (3) A positive association between sodium and BP, and a negative association between 3MH and BP were also shown in subjects who had BMI less than 26 kg/m2. In conclusion, the study confirmed and further extended previous observations on the study of salt and animal protein intake in relation to BP in middle-aged Chinese. The results support recommendations for a reduction in high salt intake for the control of high BP in the general population and in those with lower BMI. The results also provide important evidence that adequate animal protein intake may have a favorable effect on BP.

Aging↗

Assessment of in vivo oxidative stress in hypertensive rats and hypertensive subjects in Tanzania, Africa.

Oxidative stress has been reported to be involved in not only cardiovascular diseases but in hypertension, which is a major risk for cardiovascular diseases. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been recognized as a sensitive biomarker of oxidative DNA damage and also of oxidative stress. In the present study, we assessed the oxidative stress in human subjects with hypertension and in hypertensive rats. In stroke-prone spontaneously hypertensive rats at the age of 14 weeks, the excretion of urinary 8-OHdG was significantly (p < 0.05) increased compared with that in age-matched normotensive Wistar-Kyoto rats. Next, we investigated the relationship between oxidative DNA damage and cardiovascular risk factors among Tanzanians aged 46-58 years in a population study carried out in 1998 in at Dar es Salaam, Tanzania, according to the WHO-CARDIAC Study Protocol. Sixty subjects (male/female, 28/32) were selected by SPSS Base 8.0 from those who completed a 24-h urine collection. The 24-h urinary 8-OHdG of the hypertensive subjects (SBP > or =140 mmHg and/or DBP > or =90 mmHg) was significantly (p < 0.05) higher than that of the normotensive subjects (SBP <140 mmHg and DBP <90 mmHg) after adjusting for age and gender (Hypertensives: 17.31 +/- 2.0 ng/mg creatinine, n=38; Normotensives: 10.10 +/- 2.64 ng/mg creatinine, n=22). Oxidative stress was thought to be involved in hypertensive subjects and in hypertensive rats.

8-Hydroxy-2'-Deoxyguanosine↗

Angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism in hypertensive patients with different degrees of obstructive sleep apnea.

To investigate the role of the angiotensin-converting enzyme gene (ACE) insertion (I)/deletion (D) polymorphism in hypertensive patients with different degrees of obstructive sleep apnea (OSA). A case-control study was performed. One hundred seventy four Chinese subjects were divided into four groups depending on the severity of OSA as follows: 1) normal control group (NC, n=68), 2) isolated hypertension group (HT, n=45), 3) hypertensive patients with mild OSA group (MO, n=27), and 4) hypertensive patients with moderate to severe OSA group (MSO, n=34). The distribution of ACE gene I/D allele and genotypes were analyzed in the subject population, as was an OSA pedigree. The study showed that the frequency of ACE gene I/D polymorphism differed significantly among the four groups. The frequency of I allele and II genotype were significantly higher in the MSO group than in the other groups (p<0.05). The distribution of I allele and II genotype showed no significant difference between any of the other groups (p>0.05, respectively). Meanwhile the higher frequency of I allele and II genotype was observed in the OSA pedigree. The higher frequency of ACE gene I allele and II genotype were closely associated with the hypertensive patients with MSO. The inherited factors played an important role in the pathogenesis of hypertensive patients with MSO.

Adult↗

Comparative studies of diet-related factors and blood pressure among Chinese and Japanese: results from the China-Japan Cooperative Research of the WHO-CARDIAC Study. Cardiovascular Disease and Alimentary Comparison.

We aimed to compare the differences in diet-related factors and their associations with blood pressure (BP) between Chinese and Japanese. A total of 1,151 Chinese (M/F: 551/600) and 1,681 Japanese (782/899), aged 48-56 years, were studied using a multi-center cross-sectional study design. This work was a constituent part of the World Health Organization (WHO) Cardiovascular Disease and Alimentary Comparison (CARDIAC) Study. Measurements included in the present report were BP, body mass index (BMI), serum total cholesterol (TC), 24-h urinary sodium, potassium, calcium, magnesium, creatinine, 3-Methylhistidine (3MH, a marker of animal protein intake) and taurine (a marker of seafood intake) excretion levels. Results were as follows: (a) Japanese men had a significantly higher prevalence of hypertension than the Chinese (34.4% vs. 20.5%, p<0.01). After adjustment for age, Japanese men had a significantly higher mean systolic and diastolic BP (SBP, DBP), and Japanese women had a significantly higher DBP than the Chinese subjects overall (p<0.01, respectively). (b) Japanese had significantly higher mean BMI, TC and sodium excretion, and lower mean magnesium excretion than Chinese (p<0.01). (c) In the Japanese sample, multiple linear regression analyses (using a stepwise procedure) showed that SBP had a significant positive association with BMI and sodium excretion, and a significant negative association with magnesium excretion, while DBP had a significant positive association with BMI and a significant negative association with the 3MH to creatinine ratio (3MH/Cre). In the Chinese sample, both SBP and DBP showed a significant positive association with BMI and sodium, and a significant negative association with 3MH/Cre. In conclusion, Japanese had significantly higher mean BP than Chinese. The differences in BP may have been partly attributable to differences in various diet-related factors, particularly in BMI, sodium, magnesium-rich foods and animal protein intake, between the two populations.

Blood Pressure↗

Plasma endothelin-1 levels and circulating endothelial cells in patients with aortoarteritis.

To investigate the correlation between plasma endothelin-1 (ET-1), circulating endothelial cells (CECs), and the disease activity in patients with aortoarteritis. In this study, radioimmunoassay was used to measure plasma levels of ET-1 in 56 patients with aortoarteritis. Circulating endothelial cell counts were also carried out as an indicator of vessel wall lesions. The plasma levels of ET-1 and CECs in the active disease patient group were significantly higher than those in inactive patient group (p<0.001). A significant positive correlation was found between plasma ET-1 levels and erythrocyte sedimentation rates (ESRs) in patients with aortoarteritis (r=0.645, p<0.001), as well as CECs (r=0.876, p<0.001). These results suggested that the ET-1 secreted during the active stages of aortoarteritis may cause constriction and proliferation of vascular smooth muscle cells, thus contributing to the pathogenesis of luminal narrowing. The increased CECs might serve as a marker of disease activity.

Adult↗

Optical detection of triggered atherosclerotic plaque disruption by fluorescence emission analysis.

Fluorescence emission analysis (FEA) has proven to be very sensitive for the detection of elastin, collagen and lipids, which are recognized as the major sources of autofluorescence in vascular tissues. FEA has also been reported to detect venous thromboemboli. In this paper we have tested the hypothesis that FEA can reproducibly detect in vivo and in vitro triggered plaque disruption and thrombosis in a rabbit model. Fluorescence emission (FE) spectra, recorded in vivo, detected Russell's viper venom (RVV)-induced transformation of atherosclerotic plaque. FE intensity at 410-490 nm 4 weeks after angioplasty was significantly lower (P < 0.0033 by analysis of variance) in RVV-treated rabbits when compared to control animals with stable plaque. FE spectral profile analyses also demonstrated a significant change in curve shape as demonstrated by polynomial regression analysis (R2 from 0.980 to 0.997). We have also demonstrated an excellent correlation between changes in FE intensity and the structural characteristics detected at different stages of "unstable atherosclerotic plaque" development using multiple regression analysis (R2 = 0.989). Thus, FEA applied in vivo is a sensitive and highly informative diagnostic technique for detection of triggered atherosclerotic plaque disruption and related structural changes, associated with plaque transformation, in a rabbit model.

Angioplasty, Balloon↗

pH-responsive swelling behavior of collagen complex materials.

This article deals with an natural collagen blended with chitosan, poly(vinyl alcohol)(PVA). We investigated the swelling properties of collagen and collagen complex in the solution with different pH, and the swelling/deswelling behavior of collagen and collagen-chitosan complex when changing the pH of the medium from 5.4 to 1.8 and in the reverse. The results show that the swelling degree of collagen and collagen complex are dependent to pH of the solution, and the swelling behavior of collagen and collagen-chitosan complex are pH-responsive.

Absorption↗

Design, expression, and renaturation of a lesion-targeted recombinant epidermal growth factor-von Willebrand factor fusion protein: efficacy in an animal model of experimental colitis.

In the present study, the mature epidermal growth factor (EGF) protein was engineered to incorporate a high affinity collagen-binding domain (CBD) derived from co-agulation von Willebrand factor, to specifically target EGF to colonic lesions. The fusion protein was expressed in an E. coli bacterial expression system, purified by metal chelate chromatography, and renatured by oxidative refolding into a soluble biologically active growth factor. The EGF-CBD fusion protein bound tightly to collagen matrices under conditions in which native non-targeted EGF was washed away. In biologic assays, the EGF-CBD fusion protein stimulated NIH3T3 cell proliferation with near wild-type biological activity. In vivo binding studies showed that the collagen-targeted EGF, but not the non-targeted EGF, accumulated at areas of exposed collagen on the luminal surface of the inflamed colon. Finally, a single colonic instillation of the collagen-targeted EGF-induced a more rapid regeneration of intestinal crypts 24 h after treatment (no. of crypts = 89.2+/-8.1) compared to the non-targeted EGF (no. of crypts = 52.2+/-29.8; p=0.027), and the PBS control (no. of crypts = 24. 0+/-22.9; p=0.001). Taken together, these findings indicate that intracolonic delivery of collagen-targeted EGF represents a potentially effective therapeutic strategy for acute or chronic inflammatory bowel disease.

3T3 Cells↗

Disposition and pharmacokinetics of the antimigraine drug, rizatriptan, in humans.

The absorption and disposition of rizatriptan (MK-0462, Maxalt(TM)), a selective 5-HT(1B/1D) receptor agonist used in the treatment of migraine headaches, was investigated in humans. In a two-period, single i.v. (3 mg, 30-min infusion), and single oral (10 mg) dose study with [(14)C]rizatriptan in six healthy human males, total recovery of radioactivity was approximately 94%, with unchanged rizatriptan and its metabolites being excreted mainly in the urine (89% i.v. dose, 82% p.o. dose). Approximately 26 and 14% of i.v. and oral rizatriptan doses, respectively, were excreted in urine as intact parent drug. In a second, high-dose study (60 mg p.o.), five metabolites excreted into urine were identified using liquid chromatography-tandem mass spectrometry and NMR methods. They were triazolomethyl-indole-3-acetic acid, rizatriptan-N(10)-oxide, 6-hydroxy-rizatriptan, 6-hydroxy-rizatriptan sulfate, and N(10)-monodesmethyl-rizatriptan. Urinary excretion of triazolomethyl-indole-3-acetic acid after i.v. and oral administrations of rizatriptan accounted for 35 and 51% of the dose, respectively, whereas the corresponding values for rizatriptan-N(10)-oxide were 4 and 2% of the dose. Plasma clearance (CL) and renal clearance (CL(r)) were 1325 and 349 ml/min, respectively, after i.v. administration. A similar CL(r) value was obtained after oral administration (396 ml/min). The primary route of rizatriptan elimination occurred via nonrenal route(s) (i.e., metabolism) because the CL(r) of rizatriptan accounted for 25% of total CL. Furthermore, the CL(r) was higher than normal glomerular filtration rate ( approximately 130 ml/min), indicating that this compound was actively secreted by renal tubules. The absorption of rizatriptan was approximately 90%, but it experienced a moderate first-pass effect, resulting in a bioavailability estimate of 47%.

Administration, Oral↗

A mibefradil metabolite is a potent intracellular blocker of L-type Ca(2+) currents in pancreatic beta-cells.

It has been shown that mibefradil (Ro 40-5967) exerts a selective inhibitory effect on T-type Ca(2+) currents, although at higher concentrations it can antagonize high voltage-activated Ca(2+) currents. The action of mibefradil on Ca(2+) channels is use- and steady-state-dependent and the binding site of mibefradil on L-type Ca(2+) channels is different from that of dihydropyridines. By using conventional whole-cell and perforated patch-clamp techniques, we showed that mibefradil has an inhibitory effect on both T- and L-type Ca(2+) currents in insulin-secreting cells. However, the effect on L-type Ca(2+) currents was time-dependent and poorly reversible in perforated patch-clamp experiments. By using mass spectrometry, we demonstrated that mibefradil accumulates inside cells, and furthermore, a metabolite of mibefradil was detected. Intracellular application of this metabolite selectively blocked the L-type Ca(2+) current, whereas mibefradil exerted no effect. This study demonstrates that mibefradil permeates into cells and is hydrolyzed to a metabolite that blocks L-type Ca(2+) channels specifically by acting at the inner side of the channel.

Calcium Channel Blockers↗

Patients with both pancreatic adenocarcinoma and melanoma may harbor germline CDKN2A mutations.

Germline mutations of the CDKN2A tumor suppressor gene have been identified in melanoma kindreds linked to 9p21, and pancreatic adenocarcinoma is the second most common malignancy in some of these families. We hypothesized that unselected patients with both primary cancers, i.e., pancreatic cancer and malignant melanoma, have a genetic predisposition to tumor development, and that this susceptibility may be due to germline CDKN2A mutations. Fourteen patients, with both pathologically verified pancreatic adenocarcinoma and melanoma, were assessed for germline CDKN2A mutations by polymerase chain reaction amplification and sequencing of six overlapping fragments encompassing exons 1alpha and 2. A yeast two-hybrid assay was used to assess the functional consequences of CDKN2A variants. Germline CDKN2A mutations were identified in 2/14 patients: I49S, a novel substitution in exon 1alpha, and M53I, a previously reported missense mutation in exon 2. Both variants lead to compromised CDKN2A function. We conclude that the occurrence of both pancreatic cancer and melanoma, in the same patient, signals an inherited susceptibility to cancer, and that this predisposition is, in some cases, due to germline CDKN2A mutations. This finding has important implications not only for the proband, but also for other family members.

Adenocarcinoma↗

Effects of intestinal endotoxemia on pathogenesis of liver injury induced by thioacetamide.

OBJECTIVE: To study the effect of intestinal endotoxemia on pathogenesis of liver injury induced by thioacetamide (TAA). METHODS: Twenty-six male Wistar rats were divided into 4 groups, namely: normally control group (N), colectomy control group (C), colectomy+TAA group (C+T), TAA group (T). The changes in plasma biochemistry were measured. RESULTS: Plasma endotoxin levels were significantly higher in TAA group than normally control group. Plasma endotoxin levels in colectomy+TAA group were close to that of normally control group. Plasma ALT activity in colectomy+TAA group increased significantly compared with that of normal control group, but markedly lower than that in TAA group. Plasma endotoxin levels were positively correlated to ALT activity in T and C+T groups (r=0. 985, P<0.01). CONCLUSION: TAA itself has a deleterious effect to hepatic cells. It can also induce intestinal endotoxemia in which the liver injury is more inclined to occur and severe.

Alanine Transaminase↗

Novel trypanosomatid small nucleolar RNAs that guide methylation: their genome organization, expression and potential use to direct specific methylation on target RNA molecules.

Trypanosomatids are the causative agent of several major parasitic diseases including African trypanosomiasis, American trypanosomiasis, and leishmaniasis. These parasites possess unique RNA-processing mechanisms including trans-splicing of pre-mRNA and RNA editing of mitochondrial transcripts. In this study, we identified a trypanosomatid novel group of small nucleolar RNAs that belong to the box C/D snoRNA, which were shown to guide ribose methylation on rRNA. Three snoRNA genes were identified; snoRNA-2 carrying a single snoRNA and g2 and b2 coding for a single or multiple snoRNAs, respectively. Mapping of the methylation sites guided by snoRNA-2 using two different approaches suggest that snoRNA-2 has the potential to guide methylation on both 5.8S and 18S rRNAs. The trypanosomes follow the same guide-methylation rule established for yeast and for mammals. As a first attempt to change the methylation pattern of target RNAs, we generated transgenic parasites carrying the B2 and snoRNA-2, which were engineered to shift the methylation site on rRNA. Despite efficient expression of these tagged snoRNAs, the novel methylation site was not generated. However, efficient expression of tagged snoRNAs in transgenic parasites opens the possibility of engineering novel methylation sites on different target RNAs in vivo.

Animals↗

[Transcriptional expression of apoptosis suppression gene bcl-2 in non-small cell lung carcinoma].

OBJECTIVE: To investigate the role of Bcl-2 gene in oncogenesis and progression of non-small cell lung carcinoma(NSCLC). METHODS: The mRNA expressions of Bcl-2 gene in a series of 137 pulmonary tissues collected at various sites and with different properties were studied with Northern hybridization and non-radioactive digoxigenin labeling and detection system. RESULTS: According to the observations on benign lesions, non-cancer tissues distant from tumour, para-tumour tissues and cancer tissues, there was a tendency of mRNA expression increasing of Bcl-2 gene. Among them, Bcl-2 mRNA expression in lung cancer tissues was significantly increased, compared with that in benign lesions and tissues distant from tumour (P<0.01). The Bcl-2 mRNA expression in lymph node with cancer metastasis was significantly higher than that in lymph node without cancer metastasis(P<0.05). The Bcl-2 mRNA expression was relative to cell differentiation of the cancer, but not to the histological classification. CONCLUSION: Over expression of Bcl-2 gene might be involved in the oncogenesis and metastasis of NSCLC.

Carcinoma, Non-Small-Cell Lung↗