Biomedical subjects

J Fang

Publications and source records attributed to J Fang.

At least 127 records · Page 7Linked to original sources

PubMed2000

Dietary potassium intake and stroke mortality.

BACKGROUND AND PURPOSE: An inverse relationship of dietary potassium to stroke mortality in a small community has been previously reported. To further assess this association in a larger sample, we examined data from the first National Health and Nutrition Examination Survey (NHANES I) Epidemiological Follow-up Study. METHODS: We analyzed baseline data during 1971-1975 and follow-up through 1992. Dietary potassium intake, determined by 24-hour dietary recall at baseline, was available for 9866 subjects. Stroke mortality was recorded through 1992 follow-up. RESULTS: Mean age and dietary potassium at baseline were 55 years and 2084 mg/d; blacks reported significantly lower potassium intake than whites (1606 versus 2178 mg/24 h). During an average of 16.7 years of follow-up, there were 304 stroke deaths. For men, stratified by tertile of dietary potassium intake, age-adjusted stroke mortality rates per 1000 person-years for the lowest dietary potassium group were significantly higher than for the highest intake group, for both whites (1.94 versus 1.17; relative risk, 1.66; 95% CI, 1.32 to 2.14) and blacks (5.08 versus 1.19; relative risk, 4.27; 95% CI, 1.88 to 9. 19). For women, there was no significant difference in stroke mortality between similar levels of potassium intake for either whites (1.61 versus 1.42; relative risk, 1.13; 95% CI, 0.84 to 1.66) or blacks (2.46 versus 3.04; relative risk, 0.80; 95% CI, 0.21 to 2. 01). After stratification by hypertensive status, stroke mortality rates were significantly different by tertile of dietary potassium only for hypertensive men. There was no stroke mortality difference by potassium intake among hypertensive women or nonhypertensive men and women. Multivariate analysis, in which we controlled for caloric intake and other baseline cardiovascular risk factors, revealed that only among black men and hypertensive men was lower dietary potassium intake a predictor of stroke mortality. CONCLUSIONS: The previous finding of an association of increasing dietary potassium intake with decreasing stroke mortality has been detected only among black men and hypertensive men in this study.

Adult↗

PubMed2000

Passive and iontophoretic delivery of three diclofenac salts across various skin types.

The in vitro permeation of three diclofenac salts--diclofenac sodium (DFS), diclofenac potassium (DFP) and diclofenac diethylammonium (DFD)-across skin by both passive and iontophoretic transport were investigated. Various skin types were used as the barriers to elucidate the mechanism controlling transdermal delivery of diclofenac salts. The importance of the intercellular (paracellular) route for both DFS and DFP in passive permeation was elucidated. The transfollicular route constitutes an important permeation pathway for DFS but not for DFP. The route and mechanism for transdermal iontophoresis of DFD across the skin was somewhat different to that of the other salts. Hair follicles may be a more important pathway for DFD than for DFS and DFP under iontophoresis, while the intercellular lipid pathway showed the opposite result. Combination of iontophoresis and a penetration enhancer, cardamom oil, did not show a synergistic effect on diclofenac salt permeation. The results of this investigation suggest that the transdermal mechanism and the route of diclofenac salt uptake via passive and iontophoretic transport can be affected by their counterions.

Animals↗

PubMed2000

Molecular basis and characterization of the hyperinsulinism/hyperammonemia syndrome: predominance of mutations in exons 11 and 12 of the glutamate dehydrogenase gene. HI/HA Contributing Investigators.

Glutamate dehydrogenase (GDH) is allosterically activated by the amino acid leucine to mediate protein stimulation of insulin secretion. Children with the hyperinsulinism/hyperammonemia (HI/HA) syndrome have symptomatic hypoglycemia plus persistent elevations of plasma ammonium. We have reported that HI/HA may be caused by dominant mutations of GDH that lie in a unique allosteric domain that is encoded within GDH exons 11 and 12. To examine the frequency of mutations in this domain, we screened genomic DNA from 48 unrelated cases with the HI/HA syndrome for exon 11 and 12 mutations in GDH. Twenty-five (52%) had mutations in these exons; 74% of the mutations were sporadic. Clinical manifestations included normal birth weight, late onset of hypoglycemia, diazoxide responsiveness, and protein-sensitive hypoglycemia. Enzymatic studies of lymphoblast GDH in seven of the mutations showed that all had reduced sensitivity to inhibition with GTP, consistent with an increase in enzyme activity. Mutations had little or no effect on enzyme responses to positive allosteric effectors, such as ADP or leucine. Based on the three-dimensional structure of GDH, the mutations may function by impairing the binding of an inhibitory GTP to a domain responsible for the allosteric and cooperativity properties of GDH.

Adenosine Diphosphate↗

PubMed2000

[Transfection and expression of HCV-NS(5)B gene in Huh-7 cells].

OBJECTIVE: Hepatitis C virus (HCV) is the major cause of blood-borne non-A, non-B hepatitis. An RNA-dependent RNA polymerase is encoded by HCV non-structural protein 5B (NS(5)B) gene. A full-length HCV RNA has been transfected into human hepatoma cells, and HCV NS(5)B has been expressed in E.Coli purified. But human hepatocyte line with high expression of NS(5)B has not been established yet. METHODS: The NS(5)B gene has been transfected into Huh-7 cells by Lipofectamine. The results of transfection were confirmed by PCR and Southern blot analysis, and the level of the NS(5)B protein in Huh-7 cells was detected by Western blot analysis. RESULTS: There were the NS(5)B sequence and the expression of HCV-RNA polymerase in Huh-7 cells transfected NS(5)B plasmids. CONCLUSIONS: We have established a HCV RNA polymerase expression system in Huh-7 cells that can be used to study the mechanism of HCV replication and to test gene therapy of hepatitis C.

Humans↗

PubMed2000

[Computer modeling and experimental research of interactions between two anti-hTNF alpha monoclonal antibody variable regions and hTNF alpha].

On SGI workstation, we constructed two anti-hTNF alpha McAbs by means of homologous protein-structure-prediction method. And then, on the basis of relative experimental results and the surface properties of hTNF alpha and two McAbs, we performed the docking of hTNF alpha into two anti-hTNF alpha McAbs. In order to confirm the models, we prepared two hTNF alpha mutants designed according to the binding models, analysed and predicted the possible changes in complexes resulted from hTNF alpha mutations. The experimental analysis results proved these complex models. This will make the base of our next antibody humanization and/or reshape work.

Antibodies, Monoclonal↗

PubMed2000

Transfection and expression of HCV-NS5B gene in Huh-7 cells.

OBJECTIVE: To study the mechanism of hepatitis C virus (HCV) replication and to test gene therapy for hepatitis C, a human liver cell line expressed HCV RNA polymerase has been established. METHODS: NS5B gene has been transfected into Huh-7 cells by lipofectamine. The results of transfection were confirmed by PCR and Southern blot analysis, and the level of the non-structural protein 5B (NS5B) in Huh-7 cells was detected by Western blot analysis. RESULTS: There were NS5B gene fragments and the expression of NS5B protein in Huh-7c cells transfected with pTeT-NS5B or pcDNA-NS5B plasmid. CONCLUSIONS: We have established a HCV RNA polymerase expression system in Huh-7 cells which can be further used to analyze the mechanism of HCV replication and provide a cell model for gene therapy in vitro.

Carcinoma, Hepatocellular↗

PubMed2000

[Analysis on the causes of burn among 17,339 patients].

OBJECTIVE: To find out the common causes of burn and to develop preventive measures to prevent or reduce the injury of burn. METHODS: Descriptive analysis was used to review the burn-cases in our Burn Department from 1970 to 1998 and to summarize the epidemic features and common causes of the injuries. RESULTS: From 1970 to 1998, a total number of 17 339 inpatients were seen in our Burn Department. According to the causes of injury, burn patients were categorized as heat-injured, electric-injured, chemical-injured, etc. Most patients were injured with heat, taking up 89.11% of the total patients (P < 0.01). Most of the heat-injured patients were scalded with hot water (49.31%, P < 0.01). Children being burnt, accounted for 32.82% of the total patients (P < 0.01), whom should not be ignored. CONCLUSION: Burn happens frequently in daily life, so the preventive methods should be taken seriously.

Adolescent↗

PubMed2000

[Effects of Salvia miltiorrhiza compound injection on serum endothelin, prostaglandin I2/thromboxane A2 ratio alteration following myocardial ischemia-reperfusion in patients undergoing intracardiac surgery].

OBJECTIVE: To investigate the effects of Salvia miltiorrhiza compound injection (SMCI) on serum endothelin (ET), prostaglandin I2(PGI2), thromboxane A2(TXA2), and PGI2/TXA2 ratio following myocardial ischemia-reperfusion in patients undergoing intracardiac surgery. METHODS: Twenty patients, scheduled for selective surgery, were randomly divided into the SMCI group (group A, 10 cases) and the control group (group B, 10 cases). SMCI 200 mg/kg was given intravenously in group A before starting the operation and at the time of rewarming respectively, and equivalent volumes of normal saline were administered to group B. The central venous blood samples were collected to measure the serum concentration of ET, PGI2, TXA2, and PGI2/TXA2 ratio. RESULTS: ET significantly reduced, while PGI2 and TXA2 obviously raised in both groups at the beginning (T1) of extracorporeal cardiopulmonary bypass (CPB) (P < 0.05). After cardiac ischemia-reperfusion, ET in group B increased rapidly and significantly (P < 0.05) and evidently higher than the corresponding value in group A 30 min after reperfusion (T3) till 24 hrs after reperfusion (T5). During reperfusion, PGI2 and TXA2 in group A decreased more rapidly than that of group B, while group A maintained higher PGI2/TXA2 ratio than that of group B. At T5, PGI2 and TXA2 in group A were significantly lower than those in group B, while PGI2/TXA2 ratio was higher than that in group B (P < 0.05). The serum ET level was obviously negatively correlated to PGI2/TXA2 ratio. The postoperative cardiac function recovered much better in group A than in that group B. CONCLUSION: SMCI can significantly reduce serum ET level, raise PGI2/TXA2 ratio, thus facilitate the postoperative cardiac function recovery following intracardiac surgery under CPB.

6-Ketoprostaglandin F1 alpha↗

PubMed2000

[Histological study of the local-regional invasion of pyriform sinus carcinoma].

OBJECTIVE: In order to offer the basis for the operation of the pyriform sinus carcinoma, the local-regional invasion patterns of the pyriform sinus carcinoma were investigated. METHODS: Twenty-six surgical specimens obtained from patients who undergone laryngopharyngectomy were subjected to a whole organ section study. RESULTS: Tumors located in the lateral wall of the pyriform sinus spread mainly towards the lateral wall of the hypopharynx. Tumors located in the inner wall of the pyriform sinus spread mainly towards the larynx and opposite side pyriform sinus, the paraglottic space and thyroid cartilage were particularly frequent invaded. It was rare of the invading of the cricoid cartilage. The invasion of the epiglottis and preepiglottic space across the midline had not been found. There were two invading routines, the paraglottic space and preepiglottic space. The invasion of the paraglottic space was through the aryepiglottic fold and the inner surface of the thyroid cartilage. The invading of the preepiglottic space was through the aryepiglottic fold and the upper part of the inner surface of the thyroid cartilage. CONCLUSIONS: The invading of the preepiglottic space was not the contraindication of the partial laryngectomy. It is practicable to preserve the laryngeal function in most of the patients while tumors located on the lateral or inner wall of the pyriform sinus. There was a tendency to the invading to the contralateral side in the inner wall of the pyriform or postcricoidarytenoid region. Attention should be paid to the submucosal spreading in the postcricoidarytenoid region.

Adult↗

PubMed1999

Effect of low frequency ultrasound on the in vitro percutaneous absorption of clobetasol 17-propionate.

The effect of low frequency ultrasound (20 kHz) on the permeation of clobetasol 17-propionate (CP) through skin (sonophoresis) was studied. The ultrasound was applied at either continuous or discontinuous modes and at different intensities. The results showed that low frequency ultrasound significantly enhanced the permeability of CP across hairless mouse skin in vitro. Delivering the same amount of ultrasonic energy in different modes of application markedly influenced the flux and skin residual of CP. The on/off discontinuous ultrasound had greater enhancement on CP permeation than the continuous ultrasound. The results of skin histopathology and permeation experiment using various membranes demonstrate that both disordering of stratum corneum and convective flow resulted from the cavitation effect were responsible for sonophoretic enhancement of CP. The permeation of CP through hair follicles and sweat ducts was susceptible to the application of ultrasound.

Administration, Topical↗

PubMed1999

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 1. Structure-activity relationship in dihydropyrimidinones.

Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K(i) = 0.2 nM) for alpha(1a) receptor and greater than 1500-fold selectivity over alpha(1b) and alpha(1d) adrenoceptors. The compounds were found to be functional antagonists in human, rat, and dog prostate tissues. Compound (+)-103 exhibited excellent selectively to inhibit intraurethral pressure (IUP) as compared to lowering diastolic blood pressure (DBP) in mongrel dogs (K(b)(DBP)/K(b)(IUP) = 40) suggesting uroselectivity for alpha(1a)-selective compounds.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1999

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 3. Approaches to eliminate opioid agonist metabolites by using substituted phenylpiperazine side chains.

Dihydropyrimidinones, such as 1, represent a novel class of alpha(1a) adrenoceptor antagonists with potential for the treatment of benign prostatic hyperplasia (BPH) (see part 1 of this series). Analysis of the metabolites of 1 revealed that 4-methoxycarbonyl-4-phenylpiperidine is formed as the major metabolite and is an agonist at the mu-opioid receptor. To circumvent any potential liability resulting from the metabolite, we decided to identify alternate templates devoid of agonist activity at the mu-opioid receptor to replace the 4-methoxycarbonyl-4-phenylpiperidine moiety. The present study describes the synthesis and SAR of dihydropyrimidinones linked to substituted 4-phenylpiperazine containing side chains. Compound (+)-38 was identified as a lead compound with a binding and functional profile comparable to that of 1. The putative metabolite 2-carboxamidophenylpiperazine has negligible affinity for the mu-opioid receptor.

Adrenergic alpha-Antagonists↗

PubMed1999

Design and synthesis of novel dihydropyridine alpha-1a antagonists.

A series of analogs of SNAP 5150 containing heteroatoms at C2 or C6 positions is described. Herein, we report that the presence of alkyl substituted heteroatoms at the C2(6)-positions of the dihydropyridine are well tolerated. In addition, 15 inhibited the phenylephrine induced contraction of dog prostate tissue with a Kb of 1.5 nM and showed a Kb (DBP, dogs, microg/kg)/Kb (IUP, dogs, microg/kg) ratio of 14.8/2.5.

Adrenergic Antagonists↗

PubMed1999

Role of p53 and p21waf1/cip1 in senescence-like terminal proliferation arrest induced in human tumor cells by chemotherapeutic drugs.

Exposure of human tumor cell lines to moderate doses of anticancer agents induces terminal proliferation arrest accompanied by morphologic and enzymatic changes that resemble senescence of normal cells. We have investigated the role of p53 and p21waf1/cip1 in the induction of this response in drug-treated tumor cells. Doxorubicin treatment induced the senescence-like phenotype (SLP) and its associated terminal growth arrest in wild-type HCT116 colon carcinoma cells; this response was strongly decreased but not abolished in HCT116 lines with homozygous knockout of p53 or p21. Transduction of HT1080 fibrosarcoma cells with a genetic inhibitor of p53 also decreased the induction of SLP and increased drug-induced mitotic cell death. To determine if drug-stimulated p21 expression was responsible for senescence-like growth arrest, we have expressed different levels of p21 from an inducible promoter. While high-level overexpression of p21 was sufficient to induce SLP in HT1080 cells, the levels of p21 expressed in doxorubicin-treated cells could account for only a fraction of doxorubicin-induced SLP. Our results indicate that p53 and p21 act as positive regulators of senescence-like terminal proliferation arrest, but their function is neither sufficient nor absolutely required for this treatment response in tumor cells.

Antineoplastic Agents↗

PubMed1999

Age-dependent paraparesis in WKA rats: evaluation of MHC k-haplotype and HTLV-1 infection.

Human T-cell leukemia virus type 1 (HTLV-1) infection is shown to be closely associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the occurrence of HAM/TSP was reported to be associated with MHC class II, the mechanism is still unclear. The WKA(RT1k) strain of rats was reported to develop HAM/TSP-like paraparesis after HTLV-1 infection, and was suggested to be an animal model of HAM/TSP. We asked whether MHC k-haplotype is specifically involved in the pathogenesis of paraparesis of WKA(RT1k) rats. We injected the HTLV-1 producing human T cells (MT-2 cells) intravenously into WKA(RT1k) rats and MHC congenic WKA.1L(RT1l) rats which have MHC l-haplotype of LEW rats on the WKA background. Positive antibody response to HTLV-1 antigens and presence of provirus in peripheral blood mononuclear cells confirmed that MT-2 cell-injected rats were infected with HTLV-1. Two of 13 MT-2 cell-injected WKA(RT1k) rats and five of 13 MT-2 cell-injected WKA.1L(RT1l) rats developed HAM/TSP-like hindlimb paraparesis between 16 and 26 months old. Interestingly, three of 14 MT-2 cell-uninjected WKA(RT1k) rats and four of 13 MT-2 cell-uninjected WKA.1L(RT1l) rats showed similar paraparesis between 15 and 26 months old. MHC k-haplotype is not specific to the development of paraparesis in WKA(RT1k) rats. The role of aging, genetic background, HTLV-1 infection and other factors on the development of HAM/TSP-like paraparesis in rats are discussed.

Age Factors↗

PubMed1999

Vaginocervical stimulation inhibits female-female mounting in laboratory rats.

The objective of this study was to examine how vaginocervical stimulation (VCS) affects female-female mounting in laboratory rats. After receiving sexual stimulation from the male, the latency for the female to mount another female was significantly longer than that of control females. In the absence of any copulatory stimulation, the latency to initiate mounting of another female was about 3 min. However, following three mounts or three intromissions by a male, the latency for the experimental female to initiate mounting increased to about 10 min, and ejaculation abolished mounting for almost 2 h. Once females began mounting, regardless of the copulatory stimulation they received prior to testing, their mounting rate (mounting frequency/2 h) did not differ from stimulus control females. Artificial VCS also inhibited female mounting and anesthetization of the vaginocervical area diminished the inhibiting effect of ejaculation. Taken together, the present results provide evidence that VCS can temporarily inhibit female mounting, and that the duration of the inhibition is related to the amount of VCS received. These data are interpreted within the perspective that female mounting behavior is not a sexual behavior and is consequently suppressed within the context of normal copulation.

Animals↗

PubMed1999

Short-term effects of high-dose 17beta-estradiol in postmenopausal PD patients: a crossover study.

OBJECTIVE: To examine the effect of 17beta-estradiol on the severity of the cardinal signs of PD in postmenopausal women. BACKGROUND: Although the impact of estrogens on the manifestations of PD has not been subjected to rigorous study, their use is generally thought to be associated with a detrimental antidopaminergic effect. METHODS: A double-blind, placebo-controlled, two-arm crossover study of high-dose transdermal 17beta-estradiol was conducted in eight postmenopausal women with mild to moderate PD, all but one of whom exhibited levodopa-induced dyskinesias. Patients were randomized initially to either hormonal treatment or placebo for 2 weeks, followed by a 2-week washout period, and then another 2-week crossover treatment period. Active treatment employed four skin patches each releasing 0.1 mg of estradiol daily, replaced every 2 to 3 days. RESULTS: After 10 days of treatment a significant reduction was observed in the antiparkinsonian threshold dose of IV levodopa. Mean duration and magnitude of the antiparkinsonian response to threshold or high doses of levodopa were unchanged, and dyskinesia scores were unaltered during 17beta-estradiol treatment compared with placebo. No worsening in "on" time or motor ratings with estrogen treatment was documented. CONCLUSIONS: 17beta-estradiol appears to display a slight prodopaminergic (or antiparkinsonian) effect without consistently altering dyskinesias. Standard postmenopausal replacement therapy with transdermal 17beta-estradiol is likely to be well tolerated by many female parkinsonian patients.

Administration, Cutaneous↗

PubMed1999

Quantification and interpretation of total petroleum hydrocarbons in sediment samples by a GC/MS method and comparison with EPA 418.1 and a rapid field method.

Total petroleum hydrocarbons (TPH) as a lumped parameter can be easily and rapidly measured or monitored. Despite interpretational problems, it has become an accepted regulatory benchmark used widely to evaluate the extent of petroleum product contamination. Three currently used methods (GC/MS, conventional EPA 418.1, and a rapid field method PetroFLAG) were performed to quantify the TPH content in samples collected from a site contaminated by transformer oil. To standardize the method and improve the comparability of TPH data, crucial GC-based quantification issues were examined, e.g., quantification based on internal standards (ISTD) vs external standards (ESTD), single vs multiple ISTD, and various area integration approaches. The interpretation of hydrocarbon chromatographic results was examined in the context of field samples. The performance of the GC/MS method was compared with those of EPA 418.1 and PetroFLAG. As a result, it was observed that the ISTD quantification method was preferred to the ESTD method, multiple ISTD might be better than single ISTD, and three different area integration approaches did not have a significant effect on TPH results. Evaluation of the chromatograms between a reference sample and three unknown samples showed that the extent of contamination varied appreciably with sample depth. It was also found that there existed a good positive correlation between GC/MS and both EPA 418.1 and PetroFLAG, and that EPA 418.1 produced the higher overall estimate while GC/MS and PetroFLAG resulted in lower, more statistically comparable TPH values.

Chemistry Techniques, Analytical↗