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Biomedical subjects

C Han

Publications and source records attributed to C Han.

At least 109 records · Page 6Linked to original sources

The antipsychotic drug sertindole is a specific inhibitor of alpha1A-adrenoceptors in rat mesenteric small arteries.

We have investigated the adrenergic antagonist effect of the antipsychotic sertindole in rat resistance vessels and in membranes of HEK293 cells transfected with alpha1-adrenoceptors. Segments of rat mesenteric small arteries or rat aorta were mounted on a myograph for isometric tension recording. In mesenteric small arteries, specific alpha1A-adrenoceptor antagonists (5-methyl urapidil and WB-4101 (2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane)) inhibited phenylephrine responses with high affinity (pA2 9.1 and 9.5, respectively). Chlorethylclonidine (alpha1B- and alpha1D-adrenoceptor antagonist) and BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro [4,5] decane-7,9-dione dihydrochloride, alpha1D-adrenoceptor antagonist) had little effect. This indicated that the adrenoceptor subtype in the mesenteric small arteries was of the alpha1A subtype. Sertindole inhibited the phenylephrine response of mesenteric small arteries (pA2 9.0), but had little effect on the phenylephrine response of aorta (which lacks alpha1A-adrenoceptors). The specific action of sertindole on alpha1A-adrenoceptors was supported by experiments with membranes of HEK293 (human embryonic kidney) cells transfected with the alpha1A-, alpha1B- and alpha1D-adrenoceptors. Here, with concurrent incubation, sertindole showed selective competitive inhibition of BE2254 (2-beta(4-hydroxyphenyl)-ethylaminomethyl)-tetralone) binding to alpha1A-adrenoceptors (Ki 8.9), compared to alpha1B-adrenoceptors (Ki 7.1) and alpha1D-adrenoceptors (Ki 6.8). Despite the apparent competitive action sertindole, it was not possible to wash out its antagonist effect within 6 h in the functional phenylephrine concentration-response experiments. Furthermore, in the membranes of HEK293 cells transfected with the alpha1A-adrenoceptors, binding of [125I]BE2254 was reduced by 45% following preincubation with sertindole (1 nM). We conclude that the alpha-adrenoceptors of rat mesenteric small arteries are of the alpha1A-type, and that sertindole is a specific pseudo-irreversible competitive antagonist of this adrenoceptor subtype.

Adrenergic alpha-Antagonists↗

Characterization of subtype of alpha1-adrenoceptor mediating vasoconstriction in perfused rat hind limb.

The subtype of alpha1-adrenoceptor mediating the exogenous noradrenaline-induced vasopressor response in perfused rat hind limb was determined by functional measurements and radioligand binding assays. The potencies (pA2 values) of alpha1A-adrenoceptor-selective antagonists, RS-17053 (N-[2-(2-cyclopropylmethoxy-phenoxy) ethyl]-5-chloro-alpha,alpha-dimethyl-1H-indole-3-ethanamine hydrochloride), WB 4101 (2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4 benzodioxane), 5-methyl-urapidil, and the alpha1D-adrenoceptor-selective antagonist, BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol[4.5]de cane-7,9-dione), to inhibit the noradrenaline-induced vasopressor response determined by Schild plot were 9.47 +/- 0.21, 9.48 +/- 0.19, 8.10 +/- 0.27 and 6.66 +/- 0.14, respectively, with no slope significantly different from unity. The affinities (K(i) values) of these antagonists were determined by displacement of 125I-BE 2254 (2-beta(4-hydroxyphenyl)-ethylaminomethyl)-tetralone) binding from the cloned alpha1a-, alpha1b-, alpha1d-adrenoceptor, stably expressed in human embryonic kidney (HEK) 293 cells. The pA2 values of the above antagonists correlated well with the binding K(i) values only for alphaIA-adrenoceptors (r = 0.93), but not for alpha1B-adrenoceptors (r = 0.51) and alpha1D-adrenoceptors (r = 0.13). The concentration-vasopressor response curve for noradrenaline was not significantly affected by pretreatment with 50 microM chloroethylclonidine for 30 min. The results suggest that only alpha1A-adrenoceptors mediate the noradrenaline-induced vasopressor response in perfused rat hind limb.

Adrenergic alpha-1 Receptor Antagonists↗

Screening of anticarcinogenic ingredients in tea polyphenols.

A batch of short-term tests were used to test the antimutagenic activities of Chinese green tea water extract (TWE), tea polyphenols (TP), and tea catechins (EGCG, ECG, EGC, EC). In the V79 cell forward gene mutation and V79 cell cytokinesis-block micronuclei tests, all samples showed significant inhibitory effects on mitomycin, which indicates their effects on the initiation stage of chemical carcinogenesis. However, none of the catechins and TP had effects as strong as the TWE on the basis of their relative contents in tea. Of the four catechins, ECG and EGCG were the most potent. Using the V79 cell metabolic co-operation test as an indicator for the promotion stage, TWE and TP showed weak inhibitory effects and the individual catechins showed much stronger inhibition. The test samples also showed non-specific inhibitory effects on HeLa cell growth in soft agar, which was designed to test their effects on the progression stage.

3T3 Cells↗

Pediatric carve outs. The use of disease-specific conditions as risk adjusters in capitated payment systems.

OBJECTIVE: To address the issue of adverse selection in capitated payment systems by developing a list of disease-specific pediatric conditions (i.e., "carve outs") to be considered for separate reimbursement. DESIGN: A descriptive study using a large Medicaid database. INTERVENTION: With the use of fiscal year 1993 Washington State Medicaid cost data for 302,240 pediatric patients, a list of disease-specific carve outs was developed to meet the following criteria: high cost, low variability in cost, and association with a large proportion of medical spending. RESULTS: Six-hundred seventy-three patients (0.2%) in the database had annual costs totaling $25,000 or more. Ten percent of the cases accounted for approximately two thirds of spending, while the least expensive 70% of cases made up only 15% of the expenditures. Prematurity and complications of prematurity, neoplasms, congenital heart disease, organ transplantations, congenital anomalies, and respiratory problems were general categories of disease that met our criteria for a carve out. The association of a major surgical procedure with a diagnosis increased the predictive accuracy for high cost. CONCLUSION: Lists of disease-specific carve outs such as this one can be used by Medicaid plans and other insurers who are concerned about risk selection to identify conditions for separate reimbursement in capitated payment systems.

Adolescent↗

Differential expression of two functional serine/threonine protein kinases from soybean that have an unusual acidic domain at the carboxy terminus.

Two soybean cDNA clones, SPK-3 and SPK-4, encoding putative protein kinases were isolated and characterized. Both cDNAs encoded approximately 40-kDa serine/threonine kinases with unusual stretches of acidic amino acids in their carboxy-terminal regions, which are highly homologous to PKABA1 from wheat and ASKs from Arabidopsis. These kinases are encoded by one- or two-copy genes in the soybean genome. Notably, SPK-3 and -4 showed different patterns of expression in various soybean tissues. SPK-3 is highly expressed in dividing and elongating tissues of young seedlings but relatively weakly in tissues of mature plants. In contrast, SPK-4 showed relatively high and constitutive expression in all the tissues examined except for leaf tissues of mature plants. Although various stressors, such as dehydration and high salinity, increased the expression of both genes, the induction kinetics were different. The two genes also differed in their response to abscisic acid (ABA). SPK-3 was induced but SPK-4 was not affected by exogenously supplied abscisic acid. In accordance with these expression data analysis of the activity of a chimeric SPK-3 promoter::beta-glucuronidase (GUS) reporter gene by transient expression in tobacco leaves confirmed the inducibility of SPK-3 by salt and ABA. Polyclonal antibodies raised against a recombinant SPK-4 protein produced in Escherichia coli specifically recognized both recombinant SPK-3 and -4 proteins. Kinase assays using affinity-purified SPK-4/ antibody complexes with crude soybean extracts as substrate identified specific phosphorylation of two 41 and 170 kDa soybean proteins that were phosphorylated on serine residues. Taken together, our results suggest that SPK-3, and/or SPK-4 are functional serine protein kinase(s). Furthermore, SPK-3 and -4 may play different roles in the transduction of various environmental stresses.

Amino Acid Sequence↗

Comparison of the Ca2+ movement by activation of alpha1-adrenoceptor subtypes in HEK-293 cells.

We studied the Ca2+ movement induced by activation of alpha1A-, alpha1B- and alpha1D-adrenoceptor subtypes in transfected HEK-293 cells with the fura-2 probe. All these alpha1-AR subtypes induced both Ca2+ release and Ca2+ entry. The effect on Ca2+ release in alpha1b transfected HEK-293 cells was bigger than that in alpha1a and alpha1d transfected HEK-293 cells, and the effects on Ca2+ entry were the same in alpha1a, alpha1b and alpha1d transfected HEK-293 cells. The Ca2+ entry was inhibited by 1 mM NiSO4, but not by nifedipine. Cyclopiazonic acid (CPA) produced a biphasic Ca2+ signal response in Ca2+ medium, and only induced a transient response in Ca2+-free medium. After depletion of CPA-sensitive Ca2+ pool by 10 microM CPA in Ca2+-free medium, 10 microM adrenaline (Adr) still transiently increased [Ca2+]i in three different alpha1-adrenoceptor subtype transfected HEK-293 cells. However, after depletion of adrenaline-sensitive Ca2+ pool by 10 microM Adr, CPA transiently elevated [Ca2+]i only in alpha1a and alpha1d transfected HEK-293 cells, not in alpha1b transfected HEK-293 cells. U73122, a phospholipase C (PLC) inhibitor, inhibited both Ca2+ release and Ca2+ entry induced by activation of alpha1A alpha1B and alpha1D subtypes in transfected HEK-293 cells. These results suggest that HEK-293 cell line contains two functionally separate intracellular Ca2+ pools, CPA-sensitive and Adr-sensitive pools. Activation of alpha1B-AR stimulates Ca2+ release from both CPA-sensitive and Adr-sensitive Ca2+ pools. Alpha1A and alpha1D subtypes induce Ca2+ release only from Adr-sensitive Ca2+ pool.

Animals↗

ED use of rapid lactate to evaluate patients with acute chest pain.

STUDY OBJECTIVE: To test the hypothesis that ED arrival venous lactate levels can be used to diagnose acute myocardial infarction (AMI) and to identify patients with critical illness in the triage of ED patients presenting with chest pain. METHODS: This was a prospective, double-blind, clinical study in an urban, academic ED. We enrolled a convenience sample of adult patients who had chest pain or cardiac symptoms suggesting AMI that began within 24 hours of presentation. Patients underwent standard medical management for their chest pain. Venous lactate samples were analyzed in the ED on whole blood. An abnormal lactate level of 1.5 mmol/L or higher at the time of arrival was prospectively defined as indicating the presence of acute cardiac disease. ECG findings, levels of creatine phosphokinase (CK) and CK-MB, hospital stay data, and diagnosis of AMI by the cardiology admitting team were recorded. RESULTS: Of the 129 patients included in the study, 73 had an initial lactate level of 1.5 mmol/L or higher. The mean lactate level (+/- SD) for all patients was 1.8 +/- 1.2 mmol/L. A total of 28 patients (21%) were diagnosed with AMI and had a mean lactate level of 2.2 +/- .7 mmol/L, compared with 1.7 +/- 1.3 mmol/L in those patients who were not diagnosed with AMI (P < .03). The sensitivity of this lactate level in diagnosing AMI was 96% (95% confidence interval [CI], 89% to 100%), and the specificity was 55% (95% CI, 45% to 64%). The negative predictive value of blood lactate was 98% (95% CI, 95% to 100%). Lactate was elevated independent of the duration of chest pain symptoms, with a median time from onset to sampling of 3 hours. Lactate was elevated in patients who either died or required longer than 48 hours of ICU care, compared with survivors not requiring ICU care (4.5 +/- 4.3 mmol/L versus 1.4 +/- .6 mmol/L, respectively; P < .01). CONCLUSION: The blood lactate concentration obtained on ED arrival identifies those chest pain patients with critical cardiac illness (eg, AMI, severe congestive heart failure [CHF], decompensated arrhythmias). A normal blood lactate result has a high negative predictive value for AMI. An elevated lactate level used in conjunction with ECG and history distinguishes patients with significant myocardium at risk who are likely to benefit from more urgent attention and interventions by the attending physician. Additionally, hyperlactatemia clearly correlates with mortality and the need for ICU management in the acute cardiac patient presenting to the ED.

Adult↗

compound A induces sister chromatid exchanges in Chinese hamster ovary cells.

BACKGROUND: Compound A [CF2 = C(CF3)OCH2F], a degradation product of sevoflurane [(CF3)2CHOCH2F], is a vinyl ether and may be an alkylating agent. Thus it is a potential genotoxin. METHODS: The capacity of compound A to produce sister chromatid exchanges was measured in Chinese hamster ovary cells with and without metabolic activation. Concentrations of 11 to 468 ppm compound A were applied for 2 h, the Chinese hamster ovary cells were incubated for a further 34 h in the presence of bromodeoxyuridine, and then colcemid was added to produce arrest in metaphase. Coded slides of cells were examined blindly, and 50 chromosome spreads were counted for each test concentration. RESULTS: The lowest concentration of compound A applied without metabolic activator (27 ppm) significantly increased (P < 0.001) sister chromatid exchanges, and increasing concentrations of compound A increased the incidence of exchanges. Metabolic activation did not increase the incidence of exchanges. CONCLUSIONS: Compound A increases sister chromatid exchanges at concentrations (27 ppm) obtained in low-flow systems when sevoflurane is used at concentrations approximating minimum alveolar concentration.

Anesthetics, Inhalation↗

Increase of calcitonin gene-related peptide (CGRP) release and mRNA levels in endotoxic rats.

Previously we showed that calcitonin gene-related peptide (CGRP) is released into the circulation during pathogenesis of septic shock in humans and endotoxicosis in rats and pigs. The present study examines the changes of both CGRP release and synthesis during endotoxicosis in rats. Endotoxin was administered as a bolus (5 mg/kg,i.v.) to rats lightly anesthetized with ether. Blood samples and lumbar dorsal root ganglia (DRG), neuronal cell bodies synthesizing CGRP, were taken from rats at 0, .5, 3, or 8 h after endotoxin administration. CGRP levels in plasma and the steady-state levels of mRNA for CGRP in DRG were determined by methods of radioimmunoassay and semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR), respectively. Endotoxin elevated plasma CGRP by 62%, but not mRNA at .5 h. Endotoxin increased plasma CGRP by 142% and CGRP mRNA in DRG by 36% at 3 h, and further increased plasma CGRP by 216% and CGRP mRNA in DRG by 88% at 8 h. The data suggest that both CGRP expression and release in sensory nerves are increased during development of endotoxicosis in rats. CGRP synaptic transmission may be maintained during the course of endotoxicosis in rats. DRG undergo an elevation of CGRP expression in response to endotoxicosis, presumably as an adaptation of CGRP release during the inflammation. CGRP, because of its extremely high potency in hypotensive, tachycardiac and immunosuppressive effects, may play an important role in the pathogenesis of septic shock.

Animals↗

Alterations of mRNA levels of alpha 1-adrenoceptor subtypes with maturation and ageing in different rat blood vessels.

1. Alterations of mRNA levels of alpha 1-adrenoceptor subtypes during maturation and ageing were determined by reverse transcription-polymerase chain reaction (RT-PCR) in aortae and renal, pulmonary and mesenteric arteries isolated from 3, 12 and 24-month-old rats. 2. The steady state levels for alpha 1A-, alpha 1B- and alpha 1D-adrenoceptors in aorta declined with maturation and ageing. In renal artery there was a decrease in mRNA for the alpha 1B-adrenoceptor in aged rats. However, in mesenteric and pulmonary arteries there were no changes in mRNA levels for the three subtypes of alpha 1-adrenoceptors as a result of maturation and ageing. 3. The results suggest that expression of alpha 1-adrenoceptors is changed heterogeneously in different blood vessels during maturation and ageing in rats.

Aging↗

Alterations of cardiac alpha 1-adrenoceptor subtypes in hypothyroid rats.

1. Alterations in the cardiac alpha 1-adrenoceptor and its subtypes in hypothyroid rats were studied by radioligand binding assays and reverse transcription-polymerase chain reaction (RT-PCR). Hypothyroidism was created by feeding rats with 0.2% 2-thiouracil solution instead of daily drinking water for 20 days. 2. The density of cardiac alpha 1-adrenoceptors (Bmax) was increased from 67.5 +/- 4.3 fmol/mg in control rats to 81.1 +/- 7.2 fmol/mg (P < 0.05) in hypothyroid rats. 3. Compared with control rats, in hypothyroid rats the percentages of high-affinity sites for (+)-niguldipine and 5-methylurapidil were increased from 13.8 +/- 5.6 and 31.9 +/- 6.3%, respectively, to 24.9 +/- 7.3 and 45.5 +/- 2.4%, respectively (both P < 0.05), while those for BMY7378 were decreased from 37.2 +/- 8.9 to 23.8 +/- 8.4% (P < 0.05), respectively. The percentage of high-affinity sites for WB4101 was not significantly different in control and hypothyroid rats (43.3 +/- 9.1 and 39.4 +/- 3.6%, respectively). 4. Reverse transcription-PCR experiments revealed that the steady state levels of mRNA for alpha 1A- and alpha 1B-adrenoceptors were increased, while those for alpha 1D-adrenoceptor were decreased in the hearts of hypothyroid rats. 5. The concentration-contraction response curves for noradrenaline in the presence of a beta-adrenoceptor antagonist in control and hypothyroid rats showed that the maximal response was reduced from 344 +/- 58 to 200 +/- 23 mg, respectively (P < 0.05). 6. The data suggest that in hypothyroid rats the total number of cardiac alpha 1-adrenoceptors is increased. The change is subtype-selective, with levels of alpha 1A- and alpha 1B-adrenoceptors being increased and levels of alpha 1D-adrenoceptors being reduced. Furthermore, the positive inotropic response mediated by alpha 1-adrenoceptors is reduced in hypothyroid rats.

Adrenergic alpha-Antagonists↗

Detection of human papillomavirus type 16 DNA and of antibodies to human papillomavirus type 16 proteins in children.

We have measured markers of human papillomavirus type 16 (HPV 16) infection in children (1-10 years of age) who were hospitalized for reasons unrelated to papillomavirus infection. Genital and buccal swabs obtained from 79 children were tested for the presence of HPV 16 DNA by PCR. Low-level positivity was found in 34 donors, twice as often in oral than in genital swabs. There was no sex-specific difference, but there was a trend towards a higher positivity rate with young age. Serum antibodies (IgG) were measured by ELISA based on peptides derived from the HPV 16 early proteins E4 (one peptide), E6 (two peptides) or E7 (two peptides) in 75 children and by ELISA based on virus-like particles in 66 children. Low-positivity rates were found for E6 (5.1%), E7 (2.5%) or capsid proteins (1.5%), but 20.3% of the sera reacted with the E4-specific peptide. There was no correlation between sero-positivity and the detection of HPV 16 DNA. In those instances where HPV DNA positivity in young children represents true infection and not environmental contamination, we speculate that this infection is accompanied by low-level virus replication that does not induce a measurable antibody response. Reactivity to the E4 protein is likely due to cross-reacting antibodies directed either against E4 proteins of other HPV types or against unrelated antigens.

Antibodies, Viral↗

[Splenic artery embolization for the treatment of traumatic splenic rupture].

We used splenic artery gelfoam embolization to save the spleen Seldinger's method in 20 patients with traumatic rupture of the spleen. All patients had the spleen reserved by single embolizing hemostasis satisfactorily. We delineate the method, clinical value, indication and experience of embolism-hemostasis in detail.

Adult↗

[An experimental study on the effects of lingzhi spore on the immune function and 60Co radioresistance in mice].

Lingzhi spore (2 g.kg-1.d-1, 10 times) was orally administered to mice, and studies were carried out on the carbon clearance, delayed-type skin hypersensitivity (DTH), antibody hemagglutinin value and spleen weight. The results showed that Lingzhi spore could increase the immune function, inhibit the reduction of white blood cells and raise the survival rate of mice after they were radiated by 870 rad 60Co.

Animals↗

[Antisecretory effect of dl-(15R)-15 methyl-PGE2 methyl ester (PG6E) on perfusing rats in vivo].

The antisecretion effect of dl-(15R)-15 methyl-PGE2 methyl ester (PG6E) was studied in perfusing rats in vivo. The results showed that PG6E at the dose 0.1 mg.kg-1 decreased markedly the acid secretion and antagonized the gastric acid secretion induced by histamine, pilocarpin and pentagastrin in rats. This action of PG6E appeared to be similar to that of cimetidine (40 mg.kg-1).

Animals↗

Induction of ICE and inhibition of c-fos, jun D and zif 268 in 12-month old spontaneously hypertensive rats.

A semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay was used to examine ICE, c-fos, jun D and zif 268 mRNA expression in the aortic and renal artery of 12-month old SHRs and wistar rats. Using this assay system, it was observed that the levels of aortic and renal artery expression of ICE were markedly higher in SHRs than in wistar rats. In contrast, the aortic and renal artery expression of immediate early genes (IEGs), c-fos, jun D and zif 268, were significant lower in SHRs than in wistar rats. Thus, our results suggest that differential regulation of death gene ICE and IEGs such as c-fos, jun D and zif 268 might be involved in the mechanism of pathogenesis of hypertension.

Amino Acid Isomerases↗

[Study of environmental pollution and damage of cytogenetic materials in urban residents].

Recently, epidemiologic data have indicated that the number of deaths caused by malignant tumor presented a significantly rise in Beicun countryside of Datong city. In order to understand the causes of high incidence of cancer, factors were investigated and analysed related to air, river water, drinking water, vegetables and human serum. Results showed that Benzo (a)-pyrene (Bap), total suspended particulates (TSP) in air, nitrate, nitrite in drinking water and vegetables were all significantly higher in Beicun countryside region than those in controlled countryside region, respectively (P < 0.01-P < 0.001). The micronuclei (MN) and berration nucleus (AN) rates of cultured lymphocytes were significantly higher while cpm value of unscheduled DNA synthesis (UDS) test were significantly lower than those in controlled region among residents in Beicun countryside region, respectively (P < 0.01-P < 0.001). The micronuclei, abrerration nucleus rates and cpm value of cultured lymphocytes among residents in Beicun countryside were strongly correlated with Bap, TSP, nitrite and nitrate contents in determination samples. Our results suggest that the air and water source under serious pollution may serve as an important factor causing cytogenetic damage among residents and cancer death rise in Beicun countryside.

Benzo(a)pyrene↗