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Biomedical subjects

J C Fang

Publications and source records attributed to J C Fang.

15 recordsLinked to original sources

Plasma alpha-tocopherol and coronary endothelium-dependent vasodilator function.

BACKGROUND: In the presence of atherosclerosis, the coronary endothelial vasomotor response to acetylcholine is frequently abnormal but is variable between patients. We tested the hypothesis that the plasma concentration of alpha-tocopherol is associated with the preservation of nitric oxide-mediated endothelium-dependent vasomotion. METHODS AND RESULTS: We studied 15 men and 6 women (mean age 61+/-10 years) at coronary angiography who were not taking vitamin supplements. Coronary endothelium-dependent and -independent vasomotion was assessed by intracoronary infusions of acetylcholine and nitroglycerin. The vasomotor responses were compared with the plasma concentration of alpha-tocopherol and the plasma alpha-tocopherol concentration relative to total lipid (total cholesterol plus triglycerides). The mean plasma alpha-tocopherol was 25.6+/-6.1 micromol/L, total cholesterol 193+/-27 mg/dL, triglycerides 115+/-66 mg/dL, and alpha-tocopherol to total lipid 4. 2+/-0.9 micromol. L(-1). (mmol/L)(-1). The mean vasomotor response to acetylcholine was -1% (range -33% to 28%) and to nitroglycerin 22% (range 0% to 54%). Plasma alpha-tocopherol was significantly correlated with the acetylcholine response (r=0.49, P<0.05) but not the nitroglycerin response (r=0.13, P>0.05). The acetylcholine response remained significant after adjustment for other potential sources of oxidant stress (total cholesterol, diabetes mellitus, smoking, angina class) (P<0.01). The relative concentration of alpha-tocopherol to total lipid was not related to endothelial function (r=0.24, P=0.3, n=20). CONCLUSIONS: alpha-Tocopherol may preserve endothelial vasomotor function in patients with coronary atherosclerosis. This effect may be related primarily to the action of alpha-tocopherol in the vascular wall. Further studies that assess the impact of alpha-tocopherol supplementation as therapy of endothelial dysfunction are justified.

Acetylcholine

Cholinergic blockade inhibits gastro-oesophageal reflux and transient lower oesophageal sphincter relaxation through a central mechanism.

BACKGROUND: Atropine, an anticholinergic agent with central and peripheral actions, reduces gastro-oesophageal reflux (GOR) in normal subjects and patients with gastro-oesophageal reflux disease (GORD) by inhibiting the frequency of transient lower oesophageal sphincter relaxation (TLOSR). AIMS: To compare the effect of methscopolamine bromide (MSB), a peripherally acting anticholinergic agent, with atropine on the rate and mechanism of GOR in patients with GORD. METHODS: Oesophageal motility and pH were recorded for 120 minutes in 10 patients with GORD who were studied on three separate occasions. For the first two recording periods, either atropine (15 microg/kg bolus, 4 microg/kg/h infusion) or saline were infused intravenously. MSB (5 mg orally, four times daily) was given for three days prior to the third recording period. RESULTS: Atropine significantly reduced basal LOS pressure (12.6 (0.17) mm Hg to 7.9 (0.17) mm Hg), and the number of TLOSR (8.1 (0.56) to 2.8 (0. 55)) and reflux episodes (7.0 (0.63) to 2.0 (0.43)) (p<0.005 for all comparisons). MSB reduced basal LOS pressure (12.6 (0.17) to 8.7 (0. 15) mm Hg, p<0.005), but had no effect on the frequency of TLOSR (8. 1 (0.56) to 7.5 (0.59)) and reflux episodes (7.0 (0.63) to 4.9 (0. 60)) (p>0.05). CONCLUSION: In contrast to atropine, MSB has no effect on the rate of TLOSR or GOR in patients with GORD. Atropine induced inhibition of TLOSR and GOR is most likely mediated through a central cholinergic blockade.

Adult

Chlamydia pneumoniae infection is frequent but not associated with coronary arteriosclerosis in cardiac transplant recipients.

We sought to explore the relation between Chlamydia pneumoniae, cytomegalovirus (CMV), and cardiac transplant-associated arteriosclerosis. Serologic evidence of past Chlamydia pneumoniae infection was investigated in 3 patient groups at the time of cardiac catheterization: cardiac transplant recipients (n=49), patients having coronary artery bypass grafting (CABG) (n=39), and a control group free of angiographic coronary artery disease (n=21). High Chlamydia pneumoniae immunoglobulin G titers (> or =1:160) were more frequently observed in cardiac transplant recipients (odds ratio[OR] 13.7; 95% confidence intervals [CI] 1.6 to 117.4, p <0.05) and CABG patients (OR 21.7; 95% CI 1.6 to 287.0, p <0.05) than in controls. However, high Chlamydia pneumoniae titers did not distinguish between cardiac transplant recipients with or without angiographic transplant-associated arteriosclerosis or CABG patients with or without bypass vein graft disease. Furthermore, there was no significant relation between elevated Chlamydia pneumoniae titers and the presence or progression of transplant-associated arteriosclerosis in the subgroup of patients who were also CMV positive. Yet, analysis of the same angiograms demonstrated an association between CMV infection and the recent progression of transplant-associated arteriosclerosis. Thus, patients with cardiac transplantation have evidence of past Chlamydia pneumoniae and CMV infection but Chlamydia pneumoniae does not appear to have an independent role or synergistic relation to CMV in the development of transplant-associated arteriosclerosis.

Adult

Recipient-to-donor atrioatrial conduction after orthotopic heart transplantation: surface electrocardiographic features and estimated prevalence.

Recipient-to-donor atrioatrial conduction across a suture line has been rarely reported after orthotopic heart transplantation. The relation of such conduction to symptomatic arrhythmias and its prevalence are not known. Recipient-to-donor atrioatrial conduction was demonstrated in a 28-year-old woman with paroxysmal supraventricular tachycardia 7 years after orthotopic heart transplantation. Atrial tachycardia in the recipient atria conducted 2:1 to the donor atria and was eliminated by radiofrequency catheter ablation of a left-sided atrioatrial electrical connection. The electrocardiogram at rest and during exercise, recorded before ablation of the recipient-to-donor connection, showed frequent atrial premature complexes, with variable coupling to the preceding sinus beats, and a change in P-wave morphology during exercise, which reverted to normal during the recovery period. These findings were eliminated by ablation of the recipient-to-donor connection. To determine the prevalence of recipient-to-donor atrioatrial conduction late after transplantation, we evaluated the exercise electrocardiograms of 50 subjects > 5 years after heart transplantation for these features of recipient-to-donor conduction. At least 1 feature was present in 5 subjects, and both were present in 1 subject. Electrical conduction can occur across surgical suture lines in the atria. Recipient-to-donor atrioatrial conduction may occur in < or = 10% of patients late after heart transplantation. It is a potential cause of arrhythmias that can be effectively treated with radiofrequency catheter ablation.

Adult

Noninvasive assessment of transplant-associated arteriosclerosis.

BACKGROUND: Transplant-associated arteriosclerosis is the major limitation to long-term survival in the cardiac transplant recipient, and annual surveillance angiography is used in many centers to monitor its progression. Noninvasive methods would be preferable because angiography is invasive, costly, and insensitive; however, the reliability of such methods has been questioned. METHODS: All publications relating to the assessment of the cardiac allograft by noninvasive testing were identified through MEDLINE and a review of references from the published literature on transplant-associated arteriosclerosis. RESULTS: Resting and stress ECG, radionuclide scintigraphy, echocardiography, and positron emission tomography have all been used in cardiac transplant recipients with variable results. Most techniques are insensitive, but this limitation may be improved with pharmacologic stress imaging like dobutamine echocardiography. Although insensitive, some methods have good specificity (i.e., radionuclide scintigraphy). The noninvasive measurement of absolute coronary blood flow is promising as a specific and sensitive technique but is limited by availability and cost. CONCLUSIONS: In general, noninvasive techniques to assess transplant-associated coronary arteriosclerosis are limited by variable sensitivity and specificity. However, certain methods, such as dobutamine echocardiography and radionuclide scintigraphy, can provide important adjunctive physiologic information to angiography. Such techniques can therefore help to guide the care and treatment of the cardiac transplant recipient with allograft coronary arteriosclerosis.

Coronary Angiography

Central role for CD40/CD40 ligand (CD154) interactions in transplant rejection.

Major advances have been made in understanding the expression and function of CD40 and its ligand CD154. It is now clear that CD40/CD154 interactions are critical in many aspects of the immune response, including T cell activation, T cell-dependent macrophage activation, T cell-B cell interactions and endothelial activation. Moreover, increasing evidence supports a central role for CD40/CD154 interactions in the immune processes of allograft rejection. Functional studies using blocking monoclonal antibodies have revealed beneficial effects of interupting CD40/CD154 co-stimulation in animal models of transplantation, particularly in association with interuption of the CD28/B7 pathway. A next step is to develop new therapeutic approaches to interrupting this pathway in humans, either through the development of receptor antagonists or through the understanding of intracellular signaling pathways utilized by these molecules.

Animals

Prevalence of diabetes mellitus and associated risk factors in an adult urban population in Shanghai.

A cross-sectional study was conducted in an urban population 25 years of age and older to determine the prevalence of diabetes mellitus (DM), impaired glucose tolerance (IGT), and associated risk factors. A total of 13,940 subjects was surveyed (7,042 male, 6,898 female). The prevalence (DM 2.33%, IGT 1.30) was much higher than in a 1978 study. Age-standardised prevalence was not statistically different between males and females: respectively 2.54% and 2.14% for DM and 1.42% and 1.31% for IGT. Most diabetic patients were well-educated and performed mildly intensive labour. More patients showed a family history of diabetes during youth and risk factors associated with diabetes in old age, e.g. hypertension and an overweight condition. Microalbuminuria was found in 20.26% of newly diagnosed diabetic patients, i.e. a much higher proportion than in the normal population.

Adult

CD40 and CD40 ligand (CD154) are coexpressed on microvessels in vivo in human cardiac allograft rejection.

BACKGROUND: CD40 is expressed by a wide variety of cells in the immune system, including endothelial cells. It binds to CD40 ligand ([CD40L] CD154), which was originally reported to be restricted in its expression to early-activated T cells. We report here the expression of CD40 and CD40L in human cardiac allografts. METHODS: A total of 123 consecutive biopsies from 11 human cardiac allograft recipients were analyzed by immunohistochemistry for the expression of CD40 and CD40L. The expression of CD40L was also examined in vitro in homogeneous cultures of umbilical vein endothelial cells by reverse transcriptase-polymerase chain reaction and by flow cytometry. RESULTS: CD40 was expressed at low levels, and CD40L was minimal or absent in histologically normal biopsies in the absence of CD3+ T-cell infiltrates. In rejection, the expression of CD40 increased on vascular endothelial cells and on graft-infiltrating leukocytes throughout biopsy specimens. Induced expression of CD40 was strongly associated with the presence of CD3+ T-cell infiltrates, acute rejection, and ischemic injury (P<0.05). CD40L was expressed in biopsies with rejection and was prominent on a subset of infiltrating leukocytes as well as on microvascular endothelial cells. In contrast to CD40, staining of endothelial CD40L was focal in most biopsies. Overall, the expression of CD40L correlated with the presence of CD3+ T-cell infiltrates and rejection (P<0.05), but not ischemic injury (P=0.9). To confirm that the endothelium can synthesize CD40L, we also evaluated the expression of endothelial CD40L in vitro. Cultured endothelial cells were found to express little constitutive CD40L that markedly increased after 24 hr of treatment with supernatants from phytohemagglutinin-activated peripheral blood mononuclear cells or by the cytokines tumor necrosis factor-alpha, interleukin-1a, interleukin-4, or interferon-gamma. CONCLUSION: Both CD40 and CD40L are expressed in vivo on infiltrating leukocytes and on microvascular endothelium in human cardiac allograft rejection. We suggest that endothelial cell CD40 and CD40L play a role in human cell-mediated immune responses such as cardiac allograft rejection.

Biopsy

Pathogenic mechanisms of atherosclerosis: effect of lipid lowering on the biology of atherosclerosis.

Numerous trials have demonstrated that cholesterol-lowering therapy leads to marked reductions in cardiovascular and overall mortality and in the need for coronary revascularization. Angiographic regression trials have shown that cholesterol lowering can reduce progression and, in some instances, achieve regression of coronary atherosclerotic lesions. However, recent studies have contradicted the traditional view that the clinical course of coronary artery disease is closely linked to the severity of coronary artery stenosis. It is now apparent that stenoses responsible for myocardial infarction or unstable angina are typically mild rather than severe. These observations suggest that regression may not be the principal mechanism by which cholesterol lowering affects cardiovascular risk. Two mechanisms---plaque stabilization and improved endothelial function-have been examined in this regard. Basic studies suggest that cholesterol lowering favorably alters those features of atherosclerosis that promote plaque stability. Recent clinical studies have clearly established that aggressive lipid-lowering therapy improves endothelial function and reduces myocardial ischemia in patients with hypercholesterolemia.

Acetylcholine

[Study on the relationship between two second-messenger pathways on the regulation of proliferation and differentiation in MGc 80-3 cells].

By using an inducer of differentiation (HMBA) and blockers of signal pathways, the relationship between two second-messenger pathways (DG-PKC, cAMP-PKA) in inducer-mediated MGc80-3 cell differentiation was studied. Cells were treated with HMBA for 24 h, levels of DG decreased by 64.7%, activity of PKC decreased by 28.7%, while levels of cAMP and rate of it's protein binding increased by 62% and 32.6% respectively (after treated for 48 h, the result was more remarkable). PKA-R II distributed in nuclei. H7 (PKC inhibitor) was used to substitute for HMBA to block the DG-PKC pathway. After treatment for 24 h, the levels of DG and activity of PCK both decreased, while the levels of cAMP increased 1.04 times. On the contrary, PKA inhibitor was added while HMBA was used to induce cell differentiation, cAMP-PKA pathway was blocked, levels of cAMP and rate of it's protein binding decreased. But levels of DG and activity of PKC both increased to the levels of control cells. At this time, PKA-R II distributed only in cytoplasm. These results suggest that harmonious relations of the positive and negative regulation of cAMP-PKA and DG-PKC systems in cells during the proliferation and differentiation of cells. It also showed that positive regulation of PI system may play a leading role in MGc80-3 cells. It let to normal regulation of two signal pathway out of control to remain malignant phenotype of these cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Study on rat-rat hybridoma technique and production of rat monoclonal antibodies against HIV and HBsAg.

The rat-rat hybridoma technique has some definite advantages in the three systems (mouse, rat or human system) currently utilized for monoclonal antibody production. The study on rat-rat hybridoma technique and its application to the productions of monoclonal antibodies against human immunodeficiency virus (HIV) and hepatitis B virus surface antigen (HBsAg) are described as examples in this paper.

Animals

Diazepam and memory: evidence for spared memory function.

The effects of diazepam on several tests of memory were investigated in a double-blind study of 24 healthy young adults. Following a single oral administration of 0.3 mg/kg diazepam or placebo, subjects in the diazepam group showed marked impairment in immediate free recall of words as compared to placebo control subjects. However, diazepam-treated subjects demonstrated performance benefits from prior exposure to the same words on tests of memory priming using word completion and category-generation tasks. The two types of memory tests differ in their demand for conscious recollection. Tests of free recall have explicit (declarative) memory demands whereas the priming test places only implicit (procedural) demands upon memory. The results demonstrate that diazepam spares some forms of memory as does amnesia induced by neurological impairment.

Adolescent

Improvements in the NIOSH registry of toxic effects of chemical substances.

Subsequent to the publication of the 1977 edition of the NIOSH Registry of Toxic Effects of Chemical Substances (RTECS), several additions and changes were introduced that substantially improved the content and accessibility of the RTECS data file. Content additions included primary irritation data for both skin and eyes, in vitro mutagenicity data, and citations to toxicology review articles and to the Toxic Substances Control Act inventory. Also undertaken was a re-evalution of existing tumorigenic entries based on revised selection criteria. Accessibility to RTECS data has been facilitated by the introduction of on-line interactive computer searching, and the preparation and distribution of Computer Output Microfiche (COM-fiche) and magnetic tape copies of the file which supplement the annual publication.

Carcinogens