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Background Some genes influenced by these variants are highly expressed in vascular tissues and dysfunction can play a role in migraine. The richest tissues are part of blood vessels. In this study, a novel biomarker to predict prevalent migraine by association and mechanisms was presented. Methods Using Microarray data collection and processing and migraine summary GWAS database. Then using gene set enrichment analysis (GSEA), heuristic fine mapping by FUMA GWAS, and identification of PAM in the position of chromosome 5q21 by Pheweb of the biobank and MR-based platform. Results GSEA identified positions that were significantly increased by PAM overexpression, and gene expression was assessed in migraine patients (GSE76242). On position chromosome 5q21, modules were enriched in migraine patients with an enrichment score - 0.50, the nominal enrichment score was 1.15, and the nominal p-value (0.30142567) migraine. In FUMAGWAS, we added an analyzer for gene set analysis by enrichment. One of the GeneSets was chromosome 5q21, N was 15, n was 2, the value of P was 2.14e-4, the adjusted P was 1.60e-2, and the genes were the PAM gene and were assigned by the SNP coding area rs73189054 (lead SNP). Conclusions In conclusion, this study provides a novel migraine rs73189054 from PAM rs73189054, in the position of chromosome 5q21. In particular, it could be determined to predict the susceptibility and vulnerability of migraine.

Background The prognosis of hepatocellular carcinoma (HCC) relies mainly on histopathological imaging examinations after surgical removal of the tumor. However, the rate of tumor recurrence is still high. Defining molecular signatures comprised of a number of distinct peptide ions specific for various tumor regions may improve the classification and prognosis of HCC patients. Methods MALDI imaging technology, cluster analysis and classification software were applied to investigate patients with hepatitis B virus (HBV)-related HCC to obtain differences in protein abundance and distribution from non-tumor to tumor regions. Results A number of mass spectra obtained from non-tumor and HCC tumor sections were readily distinguishable. Progressive change was found in a distance-dependent manner from non-tumor to tumor regions within the junction section of HCC. Fourteen of the peaks were determined from non-tumor and tumor sections as classifiers to classify various non-tumor and tumor regions of the junction section of HCC. The performance of the classification test for the tumor region with a coefficient of variation (CV) of 0.16 was better than the non-tumor region, which reached a CV of 0.53. Conclusions Our findings provide peptide information pertaining to the classification of various tumor regions to supplement current histopathological analysis in tumor margins.

In this study, we aimed at producing a MFNP consist of a dielectric core encapsulated fluorescein coating by a thin gold shell, which facilitate it with highly favorable optical and chemical properties for biomedical imaging and therapeutic applications. We have composed a novel multi-functional nanodesign, Sample A3, with fluorescein encapsulated in SiO2 nanoparticles with gold shell. The A3 nanoparticles were uniform in size, no aggregation, homogeneous and stable in the solution under the SEM image system. We have also investigated its cytotoxicity to A10 human smooth muscle cell line by MTT assay, and found that the novel sample A3 were of little cytotoxic to the cells. In conclusion, we have proposed a novel method of preparing multi-functional nanoparticles assemblies, which has added fluorescein to SiO2 in a gold shell, to make it simultaneously have the functions of photothermal therapy and tracer.

Ulcerative colitis (UC) is a chronic inflammatory disorder primarily affecting the colon mucosa. Its etiology and pathogenesis remain unclear. We used 2-DE and MS to identify differentially expressed proteins among the UC active, UC inactive, nonspecific colitis, and normal colon mucosa. Thirteen down-regulated and six up-regulated proteins were identified. Of the down-expressed proteins, eight (heat-shock protein 90 (HSPA9B), heat-shock protein 60 (HSPD1), H+-transporting two-sector ATPase (ATP5B), prohibitin (PHB), mitochondrial malate dehydrogenase (MDH2), voltage-dependent anion-selective channel protein 1 (VDAC1), thioredoxin peroxidase (PRDX1), and thiol-specific antioxidant (PRDX2)) were mitochondrial proteins, three (ATP5B, MDH2, triosephosphate isomerase) were involved in energy generation, three (PRDX1, PRDX2, SELENBP1) were cellular antioxidants, and six (HSPD1, HSPA9B, PRDX1, PRDX2, PHB, VDAC1) were stress-response proteins. Transmission electron microscopy revealed pathological alterations of mitochondrial ultrastructures even before the global colonocyte changes in the UC colon mucosa. PHB, an essential mitochondrial component protein, was down-expressed in the disease active as well as inactive colon mucosa from the patients of UC, indicative of an early event of mitochondrial changes during UC development. In contrast, aberrant activation of NFAT and ectopic expression of potential immunogenic proteins (tumor rejection antigen 1 and poliovirus receptor related protein 1) were found in the UC-diseased colon mucosa. Our findings suggest the implications of colonocyte mitochondrial dysfunction and perturbed mucosa immune regulation in the pathogenesis of UC and provide potential targets for the development of a new therapy.

To determine the genetic risk factors for venous thromboembolism (VTE), this study examined 14 genetic variants from 10 hemostatic genes in 186 Taiwanese VTE patients and the same number of matched controls, which demonstrated FGA (encoding alpha fibrinogen) Thr312Ala polymorphism was the only variant significantly associated with VTE. Nine genetic polymorphisms on the fibrinogen cluster region of chromosome 4q28 were further studied, in which four FGA polymorphisms were found in strong linkage disequilibrium and were significantly associated with VTE by genotype and allele frequency analyses. Haplotype analysis showed significantly different FGA haplotype frequencies between VTE patients and controls with the haplotype F1, containing -1051G, -3A, 312Ala and TaqI duplication alleles, significantly associated with susceptibility to VTE (P = 0.001). Haplotype-pair analysis results also indicated a strong association of the haplotype-pair F1F1 with VTE in various VTE patient subgroups. In vitro functional analysis indicated that FGA -1051G, -3A and TaqI duplication alleles enhanced significantly the transcription level of FGA; however, control subjects with FGA genotypes containing these alleles had no elevated plasma fibrinogen levels. In conclusion, our experimental data indicated that functional genetic variants in FGA are risk factors for VTE in Taiwanese populations. Determination of FGA genotypes will likely contribute to primary prevention of this condition.

Salmonella enterica serovar Choleraesuis (S. Choleraesuis), a highly invasive serovar among non-typhoidal Salmonella, usually causes sepsis or extra-intestinal focal infections in humans. S. Choleraesuis infections have now become particularly difficult to treat because of the emergence of resistance to multiple antimicrobial agents. The 4.7 Mb genome sequence of a multidrug-resistant S. Choleraesuis strain SC-B67 was determined. Genome wide comparison of three sequenced Salmonella genomes revealed that more deletion events occurred in S. Choleraesuis SC-B67 and S.Typhi CT18 relative to S. Typhimurium LT2. S. Choleraesuis has 151 pseudogenes, which, among the three Salmonella genomes, include the highest percentage of pseudogenes arising from the genes involved in bacterial chemotaxis signal-transduction pathways. Mutations in these genes may increase smooth swimming of the bacteria, potentially allowing more effective interactions with and invasion of host cells to occur. A key regulatory gene of TetR/AcrR family, acrR, was inactivated through the introduction of an internal stop codon resulting in overexpression of AcrAB that appears to be associated with ciprofloxacin resistance. While lateral gene transfer providing basic functions to allow niche expansion in the host and environment is maintained during the evolution of different serovars of Salmonella, genes providing little overall selective benefit may be lost rapidly. Our findings suggest that the formation of pseudogenes may provide a simple evolutionary pathway that complements gene acquisition to enhance virulence and antimicrobial resistance in S. Choleraesuis.

Summary This study describes a case of exercise-induced myocardial ischaemia accompanied by complete atrioventricular block (CAVB). A 59-year-old man with major depression, treated with regular imipramine and lithium for 20 years, experienced syncope episodes during exercise. Exercise, testing initially, identified ST depression in the inferior leads, and later found CAVB resulting in syncope and seizure. The patient recovered completely after resuscitation. Myocardial ischaemic markers were negative, but 35% stenosis was detected in the distal left main coronary artery by angiography. The combined use of verapamil, nitrate and aspirin was treated as the possible coronary spasm. Repeat treadmill caused negative ischaemic study or exercise-induced arrhythmia, 7 days later. The pathophysiology of the very rare exercise-induced paroxysmal CAVB has been reviewed.

Previous reports have suggested that high-dose L-arginine could be used in diabetic patients as a prophylactic blocker for the initial glycation reaction of proteins by methylglyoxal (MG), a reactive dicarbonyl compound of glucose metabolism. Here, we present several lines of evidence to substantiate that this prophylactic intervention may be inappropriate and should be used with care. First, we demonstrated that when various concentrations of L-arginine (2.0-8.0 mM) were added to a fixed concentration of MG (1.56 microM) in a buffered lucigenin solution, dose-dependent generation of superoxide anion (O(-)(2))-mediated ultraweak chemiluminescence (uwCL) occurs. The suppression of uwCL generation by exogenously added superoxide dismutase further substantiated that the interaction between MG and L-arginine generated O(-)(2). This phenomenon can also be demonstrated in a serum-based system. Furthermore, when a fixed concentration of L-arginine (8.0 mM) was added exogenously to a group of sera obtained from either diabetic patients (n = 10) or their matched nondiabetic controls (n = 10), a marked discrepancy in the generation of O(-)(2)-mediated uwCL could be demonstrated (12,534 +/- 3,147 vs. 950 +/- 350 counts; p0.001). Taken together, this evidence demonstrates that the appropriateness of using high-dose L-arginine for prophylactic measures in diabetic patients may be questioned, because the inhibition of the glycation reaction between MG and proteins by high-dose L-arginine unexpectedly produces plethoric O(-)(2) as a by-product, which may subsequently aggravate the preexisting oxidative stress status of diabetic patients.

Background— The 3D structure of the atrioventricular conduction axis incorporating detailed cellular and molecular composition, especially that relating to gap-junctional proteins, is still unclear, impeding mechanistic understanding of cardiac rhythmic disorders. Methods and Results— A 3D model of the rabbit atrioventricular conduction axis was reconstructed by combining histological and immunofluorescence staining on serial sections. The exact cellular boundaries, especially those between transitional cells and atrial myocardium, were demarcated by a dense and irregular desmin-labeling pattern in conductive myocardium. The model demonstrates that the atrioventricular conduction axis is segregated into 2 connecting compartments, 1 predominantly expressing connexin45 (compact node and transitional cells) and the other predominantly coexpressing connexin43 and connexin45 (His bundle, lower nodal cells, and posterior nodal extension). The transitional zone shows unique features of spatial complexity, including a bridging bilayer structure (a deep transitional zone connecting with a superficial atrial-transitional overlay) and asymmetrical continuity (wider atrial-transitional interfaces and shorter atrial-axial distances in the hisian portion than in the ostial portion). In the latter compartment, the His bundle, lower nodal cells, and posterior nodal extension form a continual axis and longitudinal transitional-axial interface. Conclusions— Key findings of the present study are the demonstration of a distinct anatomical border between transitional and atrial cells, connection between transitional cells and both lower nodal cells and posterior nodal extension, and distinctive connexin expression patterns in different compartments of the rabbit atrioventricular conduction axis. These features, synthesized in a novel 3D model, provide a structural framework for the interpretation of nodal function.

Premature coronary artery disease is very rare and complication with thrombus formation in the left ventricle is rarer still. A 23-year-old man was admitted to hospital for recent acute myocardial infarction after being struck by a basketball eight days previously. Echocardiography identified two peduncle thrombi at the apex of the left ventricle, which were confirmed with computed tomography. The proximal left anterior descending coronary artery was totally occluded. Following two weeks of treatment with heparin and warfarin, the patient agreed to undergo a coronary artery bypass graft and thrombectomy. The ecchymosed tissue around the coronary artery implied that a trauma injury might have been the cause of the coronary artery disease in this case. This work reviews the pathophysiology and natural history of coronary artery disease in a case of very young myocardial infarction.

Objectives: Hepatic lipase (HL) is involved in the metabolism of several lipoproteins and plays a key role in reverse cholesterol transport. The aim of the current study was to test the statistical association between two HL gene promoter polymorphisms (HL-514C/T and HL-250G/A) and lipoprotein profiles in a Taiwanese–Chinese population. Methods: A sample population of 716 Taiwanese–Chinese individuals was analyzed. DNA was extracted from the blood and genotypes were determined by polymerase chain reaction, restriction enzyme digestion, and agarose gel electrophoresis. Results: Analysis of the data revealed that these two polymorphisms are in strong linkage disequilibrium (D/Dmax=0.97, P

This article describes the additional use of incremental atrial burst pacing (A1A1) and double atrial extrastimulation with a predefined fast pathway conducted A2 (A1A2A3), rather than single atrial extrastimulation (A1A2) only, to characterize typical atrioventricular nodal reentrant tachycardia (AVNRT). The authors noted an additional 32% of patients had multiple anterograde AV nodal physiology demonstrated when A1A1 or A1A2A3 protocols were deployed compared to more conventional A1A2 protocols. The A2H2max (449 +/- 147 vs 339 +/- 94 ms) and A3H3max (481 +/- 120 vs 389 +/- 85 ms) were higher in 31 patients where multiple jumps in the AV nodal conduction curve were obtained (group 1) compared to 192 patients where only single jump was obtained (group 2) (both P0.01). Postablation, the degree of reduction of A2H2max (49%) and A3H3max (50%) in group 1 was greater than in group 2 (38% and 42%, respectively, P0.05). In seven of group 1 patients in whom A1A2A3 stimulation was required to reveal multiple jumps, the A2H2max remained unchanged after ablation (237 +/- 89 vs 214 +/- 59, P0.05). A3H3max was the only parameter that shortened significantly after ablation. Generally, successful ablation resulted in loss of multiple discontinuities in A1A1/A1H1 or A2A3/A3H3 curves. In conclusion, a combination of A1A2, A1A1, and A1A2A3 are required to fully elucidate AVNRT. Significant shortening of AHmax or loss of multiple jumps after ablation indicates successful elimination of AVNRT in these patients.

This study investigated the expression of nitric oxide (NO)-synthesizing enzymes and the glial reaction in the rat hippocampal formation following sleep deprivation for 5 days. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) reactivity was markedly reduced in the hippocampal CA1, CA2 and CA3 sectors as well as in the dentate gyrus, suggesting a suppression of NO production in these areas. Microglial cells were hypertrophic and showed an up-regulation of complement type 3 receptors as determined by antibody OX-42. However, expression of major histocompatibility complex class I and II antigens, and antigen of monocyte/macrophage lineage marked by OX-18, OX-6 and ED1, respectively, was undetected. Astrocytes also displayed hypertrophied processes with enhanced glial fibrillary acidic protein (GFAP) immunoreactivity. Western blots of hippocampal tissues corroborated the above-mentioned morphological findings in that expression of NO-synthase (NOS) was decreased while that of OX-42 and GFAP was increased in the sleep-deprived rats. Since NO is thought to be involved in memory consolidation processes in the hippocampus during sleep, the inhibition of NADPH-d and NOS reactivities may account for the memory decline after long-term sleep deprivation. The concomitant reactions in microglia and astrocytes suggest the involvement of these cells in the deleterious effect of prolonged sleep deprivation.

Adriamycin is a potent, broad-spectrum chemotherapeutic agent effective against solid tumors and malignant hematological disease. The major limiting factor for adriamycin is its cardiotoxicity. Thus, the objective of this study was to investigate the role of cardiomyocyte and endothelial cell apoptosis in adriamycin-induced cardiomyopathy, in vivo and in vitro. For in vivo study, intraperitoneal injections of adriamycin were administered to nine adult male Wistar rats and normal saline to six rats as control. Eight of the nine rats in the adriamycin group, but none in the control group, developed marked ascites and DNA ladders in agarose gel electrophoresis of genomic DNA extracted from the rat hearts (P

OBJECTIVES: Elevated homocysteine (Hcy) is considered an independent risk factor for cardiovascular disease (CVD). An elevated plasma Hcy level may interact with conventional CVD risk factors to further increase vascular disease risk. Therefore, we investigated the plasma levels of Hcy, vitamin B6 status (pyridoxal phosphate and pyridoxal), and lipid profile in patients with CVD. METHODS: Possible associations between sex, age, body mass index (BMI), and waist-to-hip ratio (WHR) to levels of plasma Hcy and plasma Hcy to vitamin B6 status and lipid profile were examined. RESULTS: Plasma Hcy level, body mass index, and waist-to-hip ratio were significantly higher in patients with CVD than in controls. Male CVD patients had significantly higher plasma Hcy levels than did female patients. Plasma levels of pyridoxal phosphate and total B6 aldehyde were significantly higher in male than in female patients. Plasma Hcy levels of patients did not correlate to their plasma vitamin B6 status or to their lipid profiles. Plasma Hcy level correlated positively with age, body mass index, and waist-to-hip ratio (P CONCLUSIONS: This suggested that patients with CVD have higher levels of plasma Hcy that are influenced by sex, age, body mass index, and waist-to-hip ratio and not by their plasma vitamin B6 status and lipid profiles.

Objectives. To quantify the dynamic behavior of the heel pad in type 2 diabetic patients and age-matched healthy individuals using mathematical modeling. Background. No single parameter can fully describe the heel-pad biomechanical properties during the loading–unloading process. Design. A descriptive study using pseudoelastic modeling was conducted to simulate the heel-pad stress–strain relationship in the loaded and unloaded states. Transmission electron microscope was used to examine six heel specimens taken from amputated legs in diabetic and non-diabetic patients. Methods. Energy dissipation ratio, loading curvature, and unloading curvature were calculated from the stress–strain curve-fits. Differences in ultrastructure between the heel pad of healthy subjects and those with diabetes were described. Results. The diabetic patients had a significantly higher mean energy dissipation ratio (mean 36.1% (SD, 8.7%) vs mean 27.9% (SD, 6.1%); P < 0:001) and mean unloaded curvatures (mean 11.8 (SD, 5.1) vs mean 8.46 (SD, 2.6); P < 0:001) than those of the control group. The collagen fibrils in diabetic heel samples were ruptured with unclear striation and uneven distribution. Conclusions. The curvature parameters may explain the poor rebound phenomenon resulting in the high impact energy in diabetic heel pads. Breakdown in collagen fibrils may be responsible for this observation. Relevance These findings can be integrated into the fabrication of orthotics that dissipate excessive heel impact energy and protect against injury. 2002 Elsevier Science Ltd. All rights reserved.

Paraoxonase (PON1) is a high density lipoprotein-associated enzyme capable of hydrolyzing lipid peroxides, and thus, might protect lipoproteins from oxidation. A common polymorphism due to an amino acid substitution (Gln–Arg) at codon 191 is considered to be a major determinant of variation in serum PON1 activity. Recent studies have suggested that the PON1-191 polymorphism is an independent risk factor for coronary atherosclerosis in patients with or without diabetes mellitus. The association of PON1-191 polymorphism genotypes and coronary artery disease (CAD) among Chinese subjects in Taiwan was examined. The genotype of 218 angiographically documented CAD patients and the same number of age- and sex-matched control subjects was determined. Genotypes AA, AB and BB were present in 25 (11%), 102 (47%) and 91 (42%) of control subjects, respectively, and in 30 (14%), 96 (44%) and 92 (42%) of CAD patients, respectively ( χ 2 =0.57, P =0.75 between groups). The frequency of the A allele was 0.36 for the control group and 0.35 for CAD patients ( P =0.94). No significant differences in the PON1-191 genotype frequencies could be found between groups when multivariate logistic regression analysis was performed, or different subgroups of age, sex or risk factors were analyzed. Among control subjects, there was also no significant difference between genotypes of the PON1-191 polymorphism and various clinical and lipid variables. In conclusion, our data suggest that there is no association between the Gln–Arg 191 polymorphism of the human PON1 gene and CAD among Chinese subjects in Taiwan.

We prospectively studied the gender differences of baseline variables, therapies, and outcomes among a cohort of 369 Chinese patients with acute myocardial infarction from 1990 to 1995. There were 277 male and 92 female patients. The male gender had a younger mean (+/-SD) age (61.5+/-10.7 vs. 67.1+/-11.7 years, P

This study describes in detail the technique and results of on-line multiplane transesophageal echocardiographic guidance of balloon mitral commissurotomy in 150 consecutive patients with symptomatic mitral stenosis. The mitral valve area improved significantly and there were no in-hospital deaths, strokes, or emergency valve operations.

To understand the effects of the interaction between genetic polymorphisms and obesity on the risk of hypertriglyceridemia (HTG), two polymorphisms, an SstI polymorphism on the apolipoprotein CIII gene and a HindIII polymorphism on the lipoprotein lipase gene, were analyzed in 339 Chinese subjects with (82 cases in the HTG group) or without HTG (257 cases in the control group). Our data revealed that the frequencies of obesity, the SstI minor allele (S2), and the HindIII major allele (H+) in the HTG group were significantly higher than in the control group. Subgroup analysis revealed that the association between these two polymorphisms and HTG occurred predominantly in nonobese subjects and in subjects with the less hypertriglyceridemic genotype of another polymorphism. Multivariate logistic regression analysis showed that all three risk factors (obesity, S2-containing chromosome, and H+ homozygosity) were associated with HTG, and an interaction was found between obesity and H+ homozygosity for the occurrence of HTG. The risk of HTG increased significantly with combinations of risk factors. Subjects can be divided into low or high risk groups for HTG using such combinations. These results provide evidence of interaction between obesity and the HindIII polymorphism of the lipoprotein lipase gene on the risk of HTG.

A multicenter, double-blind, placebo-controlled trial with multifactorial design was conducted to evaluate the safety and efficacy of the calcium-channel blocker diltiazem, in a sustained release preparation, and the angiotensin converting enzyme inhibitor, lisinopril, in the treatment of elderly Chinese patients with mild-to-moderate hypertension. In addition to the hypotensive effects of combinations of both drugs compared with monotherapy, all given once daily, the effect on quality of life was also evaluated. This study consisted of a 3 x 2 multifactorial design in which 156 women and men with a sitting diastolic pressure of between 95 mm Hg and 114 mm Hg, after a 4-week placebo washout phase, were randomized to one of six treatment groups for 12 weeks of active treatment. Monotherapy with diltiazem 120 or 240 mg produced increasing reductions of systolic and diastolic blood pressure. Compared with placebo, lisinopril 10 mg had an effect intermediate between the diltiazem doses. The combinations of diltiazem 240 mg + lisinopril 10 mg and diltiazem 120 mg + lisinopril 10 mg showed increased efficacy in reducing systolic and diastolic blood pressure compared to these drug doses used in monotherapy, but the effect of the combinations was less than predicted by an additive model. Although the total number of other adverse events reported was similar for all active treatment groups compared to placebo, lisinopril-induced cough was common with an incidence of 31% after rechallenge. Premature drug withdrawal was necessary in four of 78 patients receiving lisinopril, due to intractable cough. The combination of diltiazem 240 mg and lisinopril 10 mg was significantly more effective at reducing blood pressure than either drug alone; this additive effect did not result in a higher rate of adverse effects or impairment of quality of life. Thus, combination therapy with these agents was well tolerated and resulted in increased efficacy in these elderly patients.

Objectives. Experiments were designed to determine whether coronary endothelial dysfunction after cardiac global ischemia and reperfusion could be prevented by warm blood cardioplegic solution. Background. The coronary endothelium produces endothelium-derived relaxing factor (EDRF) to prevent vasospasm and thrombosis. After ischemia and reperfusion, endothelium-dependent relaxation (EDR) is diminished as a result of G-protein dysfunction. Methods. Dogs were exposed to extracorporeal circulation in 37°C (group 1) or 28°C (groups 2 and 3). The heart was ischemic for 120 min while continuous warm blood cardioplegic solution (group 1) or intermittent cold (4°C) crystalloid cardioplegic solution (group 2) was infused into the aortic root. Cardioplegic solution was not used in group 3 animals. The heart was then allowed to function for 60 min of reperfusion. Results. Endothelium-derived relaxation in response to acetylcholine, adenosine diphosphate and sodium fluoride of the coronary rings of group 1 was significantly different from that of groups 2 and 3 but was not significantly different from that of group 4. In contrast, EDR in response to the receptor-independent calcium ionophore agonist A23187 was not significantly different between the four groups. Scanning electron microscopic studies showed that platelet adhesion and aggregation, area of microthrombi, disruption of endothelial cells and separation of the intercellular junction could be found in coronary segments of groups 2 and 3 but not in vessels of groups 1 and 4. Conclusions. These experiments suggest that cardiac global ischemia and reperfusion impair receptor-mediated release of EDRF from the coronary endothelium with G-protein dysfunction. This type of coronary endothelial dysfunction can be prevented by continuous anterograde infusion of warm blood cardioplegic solution during global ischemia. (J Am Coll Cardiol 1997;29:681–7)

Lovastatin is a popular drug for the treatment of hypercholesterolemia. Few serious complications are associated with its use although rhabdomyolysis with renal failure has been reported when lovastatin is combined with cyclosporine or other drugs following transplantation. We report the case of a patient who developed hepatopathy and rhabdomyolysis accompanied by acute renal failure after 4 weeks of lovastatin monotherapy. The pathogenesis and treatment of these complications are also discussed.

Left ventricular thrombus is one source of cardiogenic embolism. The protruding, mobile type is the highest risk subgroup but is rarely encountered. Thrombectomy is one choice of therapy, and variously recommended based primarily on the experience with myocardial infarction. We report a rare case of successful left ventricular thrombectomy for two protruding, mobile thrombi in a patient with idiopathic dilated cardiomyopathy in order to prevent repeat embolization.

Cardiac papillary fibroelastoma (CPF) is the second most common benign neoplasm of the heart. This study describes the case of an 81-year-old man who was admitted to the hospital for severe vertigo and in whom a tumor at the right ventricular outflow tract (RVOT) was identified incidentally during echocardiography. The CPF was excised smoothly following the confirmation of its position by computed tomography. The comprehensive pathologic findings of CPF were reviewed. Detailed immunohistochemical analyses of CD34 and factor VIII-related antigen were performed on the covering endocardial cells. The unique chondroid metaplasia of fibrous tissue in this CPF has never been reported. This work is the first to present an unusual CPF at the RVOT with reactive process of fibrous connective tissue.

A double-blind, placebo-controlled study was conducted to compare the efficacy and safety of low-dose (10 mg) prevastatin and squalene (860 mg), either alone or in combination therapy, with placebo in the treatment of elderly patients with hypercholesterolemia. Ambulatory elderly patients (N = 102) were assigned in randomized fashion to receive active treatment or placebo for 20 weeks after a single-blind placebo lead-in period of 8 weeks. Total cholesterol and triglyceride levels in plasma were at least 250 mg/dL and less than 300 mg/dL, respectively. Concentrations of lipids and lipoproteins were measured, and clinical laboratory tests included liver function and creatine kinase determinations. Pravastatin 10 mg daily was more effective than squalene in reducing total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides and in increasing levels of high-density lipoprotein (HDL) cholesterol. Combination therapy significantly reduced total cholesterol and LDL cholesterol and increased HDL cholesterol to a greater extent than either drug alone. Adverse events and clinical laboratory abnormalities were generally mild and transient in all groups, and all but two patients finished the study. The incidence of side effects was low; myopathy did not occur. Coadministration of pravastatin and squalene combined the specific effects of the two drugs on lipoprotein concentrations. This combination may be useful and more cost-effective in elderly patients with hypercholesterolemia, who might have a higher incidence of side effects when using larger doses of pravastatin alone.

This report presents serial echocardiographic changes recorded before and after anticoagulant therapy was administered to 2 patients with acute pulmonary embolism. Dilatation of the right ventricle, abnormal motion of the interventricular septum and mild tricuspid regurgitation were noted in both patients. The results of the echocardiogram suggested that the patients had right ventricular pressure overload resulting from pulmonary hypertension caused by an acute pulmonary embolism. Echocardiograms performed after the patients had received anticoagulant therapy revealed a normalization of the echocardiographic parameters in both patients. The reversal of the right ventricular strain pattern revealed by an echocardiogram occurred as the result of the regression of pulmonary hypertension after anticoagulant therapy. In conclusion, echocardiographic detection of right ventricular strain in patients who present acute cardiopulmonary manifestations with no previous history of severe pulmonary disease may indicate the possibility of a pulmonary embolism.

To evaluate the efficacy and safety of low dose (10 mg) pravastatin in hypercholesterolemic, hypertensive elderly subjects undergoing antihypertensive treatment, a randomized, double-blind, placebo-controlled 6-month trial was conducted. The subjects had a total plasma cholesterol of at least 250 mg/dL and had been, for at least 3 months, consuming a standard lipid-lowering diet (American Heart Association Step 1 Diet). Sixty elderly hypertensive patients randomly received placebo (n = 30) or pravastatin (n = 30) treatment. The dosage consisted of 10 mg of pravastatin daily during the 6-month trial. Over that period, in the pravastatin group, plasma levels of total cholesterol and LDL-cholesterol significantly (P < .01) dropped (-20% and -25%, respectively) compared to the placebo group. The plasma level of HDL-cholesterol increased (+5%) while triglycerides slightly decreased (-8%) (P < .05). No serious side effects occurred, and pravastatin was generally tolerated. Fasting hyperinsulinemia (11.0 +/- 0.8 v 9.3 +/- 0.7 microU/mL; P = .06) also improved, although not significantly, after 6 months of pravastatin therapy. Results from this study confirmed that a low dose (10 mg) of pravastatin daily is a safe and effective method of reducing plasma total and LDL-cholesterol in hypercholesterolemic, hypertensive elderly patients who are on concurrent antihypertensive drug therapy.

Coronary artery endothelium exhibits functional impairment after ischemia and reperfusion. Canine left anterior descending coronary arteries were exposed to ischemia (60 minutes) followed by reperfusion (60 minutes) through a left internal mammary artery graft. In organ chamber experiments, control (left circumflex coronary artery) and reperfused (left anterior descending coronary artery) arterial segments were contracted with prostaglandin F2 alpha and exposed to hypoxia (oxygen tension = 35 +/- 5 mm Hg). Reperfused coronary rings with endothelium exhibited contractions to hypoxia that were significantly greater than contractions in control rings with endothelium (+78% +/- 8% and +14% +/- 5%, respectively; p < 0.05). This phenomenon could be blocked by NG-monomethyl-L-arginine. Electron microscopic studies showed platelet adhesion and aggregation, denudation of the endothelium and disruption of the intercellular junctions, edematous subendothelial matrix, and vesiculation of the smooth muscle cells in reperfused LAD. Swelling, vacuole formation, and loss of neurofilament occurred in the nerve fibers accompanying the vessels. These phenomena were not observed in control vessels. This study demonstrates that early after coronary artery bypass grafting, hypoxia can induce coronary vasospasm mediated by an L-arginine-dependent metabolic pathway in the endothelium. The ultrastructural changes in the coronary endothelium include platelet adhesion, aggregation, and platelet-induced contraction of coronary smooth muscle. The endothelium-dependent hypoxic coronary vasospasm and ultrastructural changes in the coronary endothelium may play an important role in the pathogenesis of myocardial ischemia and infarction after coronary artery bypass grafting.

Background Acute exacerbations (AE) of serum alanine aminotransferase activities that are 5 times above the normal upper limit frequently occur during the immune clearance phase of hepatitis Be antigen (HBeAg)-positive chronic hepatitis B (CHB). It is unclear how the varying clinical severities of AE reflect differences in the underlying immune responses against the hepatitis B virus. Methods We utilized magnetic bead-based purification methods coupled with MALDI-TOF mass spectrometry to generate plasma peptide profiles from HBeAg-positive CHB patients experiencing AE without and with clinical decompensation. Results Hydrophobic interaction chromatography (HIC C18) provided a more discriminatory spectral profile than immobilized Cu2+ metal ion affinity chromatography did for diagnosis of a clinical spectrum of AEs. Using the sorting algorithm, Support Vector Machine, a classification model consisting of 5 classifiers was determined to give a sensitivity of 94.7% and a specificity of 75% for differentiating patients with and without decompensation. Classifiers identified as fragments derived from transthyretin and apolipoprotein A-IV were significantly decreased and increased in patients with decompensation, respectively. Conclusions Our study demonstrated that HIC C18 fractionation coupled with MALDI-TOF mass spectrometry can be used for differentiating AE with and without decompensation in patients with HBeAg-positive CHB.

The study was performed on 122 patients proved by catheterization to have dominant mitral stenosis so as to define proper endpoints of exercise testing for functional evaluation. This represents the 14-year experience with mitral stenosis in our exercise laboratory. Of them, we investigated 126 who completed clinically event-free Naughton treadmill exercise tests. Excess peak exercise heart rates (over 150 beats per minute, 63%) and exertional hypotensive responses (59%, probably including factitious responses due to unreliable indirect pressure readings) did not correlate with the severity of mitral stenosis. Without limiting symptoms and major ventricular arrhythmias, either of the above as endpoints may cause the test to be halted prematurely in half the cases. Ventricular arrhythmias (60%; in complex forms, 20%; possibly contaminated by aberrancy in atrial fibrillation and aggravated by digitalis/diuretics) did not correlate with severity of stenosis either, but the only one major complication we met was secondary to ventricular tachyarrhythmia. Limiting symptoms (83%; of them 94% being dyspnea/fatigue correlating with severity at P less than 0.01) and complex ventricular arrhythmias as endpoints terminated 85% of the tests safely in this series. Atrial thrombuses (34%, all non-floating) did not cause any related complications. Thus, we concluded that limiting symptoms and complex ventricular arrhythmias are the proper endpoints in evaluating the exercise capacity of patients with mitral stenosis after prior echocardiographic exclusion of those with potentially risky floating thrombus.

We reviewed our clinical experience in 24 patients with cardiac myxoma. There were 8 males and 16 females, their ages ranged from 14 to 73 (mean, 48) years. Prior to echocardiographic examination, cardiac myxoma was suspected clinically in only 2 cases. The remaining patients were initially diagnosed as having mitral valvar disease (9 cases), infective endocarditis (3 cases), congestive cardiomyopathy (4 cases), pericardial effusion (1 case), systemic embolism of unknown cause (1 case), cerebrovascular accident (2 cases), ventricular septal defect (1 case) and Ebstein's malformation (1 case). The tumor was in the left atrium in 16, in the right atrium in 2, in the biatrium in 1, while one was in the right ventricle and peripheral arterial occlusion had been produced by myxoma without demonstrable cardiac tumors in the other two. Twenty-two patients underwent open heart surgery for excision of myxoma and there was no surgical mortality. Abdominal embolectomy was carried out in 2 patients; one of these 2 patients survived and 1 died. Follow-up for a mean period of 32 months (range 2 to 99 months) was possible in 18 patients with no evidence of recurrence. We conclude that cardiac myxoma may mimic many cardiovascular diseases, so a high index of suspicion is important for its diagnosis. Echocardiography is the most useful diagnostic screening tool.

Changes in plasma levels of atrial natriuretic peptide (ANP) and albumin, and blood hematocrit (Hct) during treadmill exercise were studied in 6 healthy men before and after beta-adrenergic blockade. Plasma ANP levels increased during exercise and then gradually decreased. There was a concomitant increase in both Hct and plasma albumin concentrations. Prior administration of a long-acting propranolol, 160 mg daily for 3 consecutive days, markedly elevated plasma ANP levels before, during and after exercise. In addition, the mean basal Hct increased significantly and further rose during exercise after propranolol administration. When increments in plasma ANP concentrations during exercise in individual subjects were compared with those in Hct, there was a significant positive correlation between the two variables before and after propranolol administration. The results indicate a close relationship between the changes in plasma ANP and those in Hct during exercise at different ANP levels, and suggest that ANP may be at least one of the factors involved in the hemoconcentration associated with exercise.

An electron microscopic immunocytochemical study of left ventricular myocardium was carried out in 16 patients with heart disease of various etiologies in order to characterize the secretory granules arising in the ventricular muscle cells. The electron-dense granules observed in the ventricular muscle cells were demonstrated only in 3 patients with dilated cardiomyopathy and chronic congestive heart failure. They were scattered throughout the cytoplasm of the ventricular muscle cells at paranuclear, interfibrillar and subsarcolemmal areas, and tended to be most numerous in the vicinity of the Golgi apparatus. These granules were often found to be bound by limiting membranes of homogeneous electron density. Protein A-gold electron microscopic immunocytochemistry with anti-α-human atrial natriuretic polypeptide resulted in specific staining of the granules. These findings, taken together indicate that the secretory granules containing atrial natriuretic polypeptide (ANP) exist in the ventricular muscle cells in a particular category of patients with dilated cardiomyopathy and chronic congestive heart failure. Thus, it is suggested that human ventricular muscle cells have retained the genetic ability to form specific ANP-containing granules in certain clinical disorders.

Two-dimensional (2-D) and Doppler echocardiographic features of three cases of coronary arteriovenous fistula (CAVF) were analyzed. The final diagnosis was confirmed by coronary angiography in each case. In cases 1 and 2, the CAVF arose from the right coronary artery and drained into the right atrium and right ventricle, respectively. The origin and draining site of the CAVF could be visualized by 2-D echocardiograms. The Doppler studies revealed a unidirectional flow within the lumen of the CAVF. In case 3, with a small CAVF originating from both the right coronary artery and left circumflex artery draining into the main pulmonary artery, no abnormal vascular structure could be detected by the 2-D echocardiogram; with Doppler study, a diastolic as well as systolic flow signal directed toward the distal pulmonary artery could be detected.

High-resolution electron microscopic investigation of cholesterol monohydrate crystals obtained from human atheroma was carried out for the purpose of characterization of the crystal lattice, demonstration of crystallization processes and identification of crystal disorders. By high-resolution electron microscopy the crystal structures of perfect cholesterol monohydrate crystals were characterized as regular lattice arrays which consisted of stacks of repetitive rod-shaped substructures ca 1.58 nm long and 0.16 nm wide, with the total thickness of bilayered substructures ca 3.36 nm. These substructures were in an end-to-end arrangement of approximately side-to-side parallel packing, with a centre-to-centre spacing ca 0.32 nm. At the atomic level the lattice arrays were made up of regularly spaced rows of dots ca 0.28 nm × 0.16 nm in size. These dots possessed a six-fold ring-like shape, and were arranged in a hexagonal structure with an additional dot in the centre. High-resolution electron microscopic observations of the partially crystallized particles of cholesterol monohydrate showed various stages of cholesterol crystallization, from very small short-ordered segment of lattice arrays to different sized nano- and microcrystallites in the amorphous matrix of the crystals. Furthermore, crystal growth was also demonstrated from detailed examination of the crystal surfaces, the interfaces between the crystals and the boundary structures between the amorphous and crystalline phases. In addition, high-resolution electron microscopy could clearly identify various kinds of crystal defect in the cholesterol monohydrate crystals, including considerable variations of lattice spacings with focal fragmentation of lattice fringes, derangement of atom-sized dots along the lattice fringes and marked alterations of the morphology of atom-sized dots with the vacancies along the lattice arrays. It is hoped that such information obtained from high-resolution electron microscopic observations of the crystalline cholesterol in human atheroma at the atomic or near-atomic level may be helpful by providing a more complete understanding of the pathogenetic mechanisms responsible for the formation, progression and regression of the acellular lipid-rich cores of advanced atherosclerotic plaques.

The present study was carried out to investigate the protective effects of Danshen (DS, Salvia miltiorrhiza) on adriamycin (ADR)-induced cardiac and hepatic toxicity. Wistar rats were divided into six groups: control group, 10 animals received saline (i.p.); 15 animals received ADR (3 mg/kg, i.p.) three times weekly, for 2 weeks; 10 animals each received DS(1) (20 mg/kg, oral) and DS(2) (100 mg/kg, oral) for 30 days; 15 animals each received DS(1) + ADR and DS(2) + ADR. The ADR-induced cardiac and hepatic toxicity and protective action of DS were determined and quantitated with the use of hemodynamic measurements, biochemical analyses of serum, synthesis rates of DNA, RNA and protein, myocardial antioxidants, lipid peroxidation and histopathological procedure. Liver function was damaged. Nucleic acid as well as protein synthesis was inhibited, while lipid peroxidation was increased. Myocardial glutathione peroxidase (GSHPx) activity and superoxide dismutase activities (SOD) were decreased and histopathology revealed myocardial lesions indicative of ADR-induced cardiac and hepatic toxicity. In contrast, administration of DS before and concurrent with ADR significantly attenuated these effects. In conclusion, DS is potentially protective against ADR-induced cardiac and hepatic toxicity.

We describe the genome sequence of the protist Trichomonas vaginalis , a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the ∼160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated in pathogenesis and phagocytosis of host proteins may exemplify adaptations of the parasite during its transition to a urogenital environment. The genome sequence predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria.

The traditional Chinese medicine prescription "Sheng-Mai-San (SMS)" has been used for treating patients with coronary heart disease for a long time and was found to have antioxidative effects. Here, we applied adriamycin (doxorubicin, ADR), a highly effective anticancer agent, as an inducer to establish the animal model of dose-related cardiomyopathy due to inhibition of nucleic acid as well as protein synthesis, formation of free radicals, and lipid peroxidation. The objective of this study was to investigate the protective effects of SMS on adriamycin-induced cardiomyopathy. Wistar rats were divided into four groups: CONT (control), ADR, SMS, and ADR + SMS. ADR (cumulative dose, 15 mg/kg) was administered to rats in six equal intraperitoneal injections over a period of 2 weeks and SMS was administered via a feeding tube throughout the mouth once a day for 30 days (cumulative dose, 150 g/kg). At the end of the 5-week post-treatment period, the hearts of the rats were surgically removed for the study of synthesis rates of DNA, RNA and proteins. Besides myocardial antioxidants, lipid peroxidation and morphological ultrastructure were also evaluated. Three weeks after the treatment, cardiomyopathy and congestive heart failure were characterized according to assessment in ascites, congested liver, depressed cardiac function and myocardial cell damage. The results demonstrated that nucleic acid as well as protein synthesis was inhibited, while lipid peroxidation was increased. Myocardial glutathione peroxidase (GSHPx) activity was decreased and electron microscopic examination revealed myocardial lesion indicative of ADR-induced cardiomyopathy. In contrast, administration of SMS before and concurrent with ADR significantly attenuated the myocardial effects. It also lowered mortality as well as the amount of ascites. In addition, indexes in myocardial GSHPx, macromolecular biosynthesis and superoxide dismutase activities were increasing, with a concomitant decrease in lipid peroxidation and preserved myocardial ultrastructure. These results indicated that SMS may be partially protective against ADR-induced cardiomyopathy.

We studied the electrophysiological and antiarrhythmic actions of HA-7 [N-benzyl-7-methoxy-2,3,4,9-tetrahydrofuro[2,3-b]quinoline-3,4-dione], a furoquinoline alkaloid derivative, in guinea pig heart preparations. In the perfused whole heart model, HA-7 caused a prolongation in the basic cycle length, ventricular repolarization time, and the atrioventricular (AV) nodal Wenckebach cycle length and prolonged the refractory period of the atrium, AV node, and His-Purkinje system. The atrioventricular conduction interval was also prolonged in a frequency-dependent manner. In isolated hearts, HA-7 significantly raised the threshold for experimental atrial fibrillation and reduced the occurrence of reperfusion-induced ventricular fibrillation. Conventional microelectrode-recording study shows that HA-7, but not d-sotalol, prolonged the action potential duration (APD) and decreased the maximum rate of depolarization in isolated atrial strips. In ventricular papillary muscles, higher concentrations of HA-7 caused a prolongation of APD(90) in a frequency-independent manner, whereas d-sotalol exerted a reverse frequency-dependent action on this parameter. Whole-cell patch clamp results on ventricular myocytes indicate that HA-7 decreased both the slow (I(Ks)) (IC(50) = 4.8 muM) and fast component (I(Kr)) (IC(50) = 1.1 muM) of the delayed rectifier K(+) currents. Similar results could also be observed in atrial myocytes. The inward rectifier K(+) current (I(K1)) was also reduced somewhat by HA-7. HA-7 also suppressed the Na(+) inward current (I(Na)) (IC(50) = 2.9 muM) and inhibited the L-type Ca(2+) current (I(Ca)) (IC(50) = 4.0 muM, maximal inhibition = 69%) to a lesser extent. We conclude that HA-7 blocks multiple ionic currents and that these changes affect the electrophysiological properties of the conduction system as well as the myocardial tissues and may contribute to its antiarrhythmic efficacy.

Background Severe acute respiratory syndrome (SARS), a recent epidemic human disease, is caused by a novel coronavirus (SARS-CoV). First reported in Asia, SARS quickly spread worldwide through international travelling. As of July 2003, the World Health Organization reported a total of 8,437 people afflicted with SARS with a 9.6% mortality rate. Although immunopathological damages may account for the severity of respiratory distress, little is known about how the genome-wide gene expression of the host changes under the attack of SARS-CoV. Results Based on changes in gene expression of peripheral blood, we identified 52 signature genes that accurately discriminated acute SARS patients from non-SARS controls. While a general suppression of gene expression predominated in SARS-infected blood, several genes including those involved in innate immunity, such as defensins and eosinophil-derived neurotoxin, were upregulated. Instead of employing clustering methods, we ranked the severity of recovering SARS patients by generalized associate plots (GAP) according to the expression profiles of 52 signature genes. Through this method, we discovered a smooth transition pattern of severity from normal controls to acute SARS patients. The rank of SARS severity was significantly correlated with the recovery period (in days) and with the clinical pulmonary infection score. Conclusion The use of the GAP approach has proved useful in analyzing the complexity and continuity of biological systems. The severity rank derived from the global expression profile of significantly regulated genes in patients may be useful for further elucidating the pathophysiology of their disease.

Recently, a T/C polymorphism of the promoter region of the APOA5 gene at position -1131 and a G/T polymorphism at position 553 were found to be associated with increased levels of plasma triglyceride. Triglyceride plays a role in coronary artery disease (CAD), so this case-control study tested for a possible link between these two APOA5 polymorphisms, their common haplotypes and the risk of CAD. The subjects included 211 CAD patients and 677 unrelated controls. A significantly higher level of triglycerides and a lower level of high-density lipoprotein cholesterol (HDL-C) were noted for carriers with -1131C than for non-carriers (P0.001 and 0.013, respectively) among controls. Plasma triglyceride levels were significantly higher (P=0.014) in controls with genotypes that contained the c.553T allele than in homozygotes for the G allele. Subjects homozygous for the wild-type haplotype had significantly lower triglyceride levels and higher HDL-C levels than subjects with all other haplotype pairs. The -1131C homozygous carriers and c.553T heterozygous carriers were found more frequently in 211 patients with CAD than in the 317 age/sex-matched controls (P=0.008 and 0.023, respectively) in univariate analysis. The significant association between c.553T allele carriers with CAD remained in multivariate regression analysis (OR, 1.79; CI, 1.07-3.00; P=0.028), after adjustments were made for other risk factors. Notably, haplotype analysis further verified that the APOA5 -1131C and c.553T bi-loci haplotype was significantly overpresented in CAD, as compared to the controls. These results indicate that the variants of APOA5 gene modulate plasma triglyceride and may use them to predict CAD susceptibility in Taiwanese Chinese.

Electrophysiological characteristics of an accessory pathway (AP) with a long ventriculoatrial (VA) interval (arbitrarily defined as > or = 50 ms and absence of continuous electrical activity) and no retrograde decremental property are described in this study. Fifteen patients (group 1) were compared with 171 patients with normal VA conduction (group 2). Mean VA conduction time was 77 +/- 24 versus 34 +/- 12 ms in group 1 versus group 2, respectively. Group 1 patients were older (55 +/- 14 vs 40 +/- 14 years), the male to female ratio was higher (2.8 vs 1.6), and APs were more prevalent on the right (60%) but manifest APs were lower (20% vs 54%) compared to group 2 patients (P < 0.05 in all cases). QRS morphology during induced atrioventricular reciprocating tachycardia was identical in both groups but the tachycardia cycle length was longer in group 1 (373 +/- 29 vs 344 +/- 50 ms, P < 0.05). Retrograde AP block cycle length and effective refractory period were greater in group 1 (362 +/- 59 vs 293 +/- 57 ms; 330 +/- 58 vs 273 +/- 55 ms, both P < 0.05). Adenosine (up to 18 mg) and verapamil (5-10 mg) failed to block the VA conduction via AP during ventricular pacing. In group 1 the number of radiofrequency lesions for a successful ablation were significantly less (3 +/- 2 vs 6 +/- 5, P < 0.05). In conclusion, APs with a long VA interval and no decremental retrograde conduction have electrophysiological characteristics that are different from those with a short VA interval. Role of aging deserves further exploration.

Advances in molecular and computational biology have led to the development of powerful, high-throughput methods for analysis of differential gene expression, which are opening up new opportunities in genomic medicine. DNA microarray technology has been enthusiastically integrated into basic biomedical research and will eventually become a molecular monitoring tool for various clinical courses.As a core research facility of Chang Gung University (CGU) and Chang Gung Memorial Hospital (CGMH), the Genomic Medicine Research Core Laboratory (GMRCL) welcomes investigators from every discipline to employ DNA microarray technology in the quest for knowledge of genomic medicine. The first tasks for GMRCL are to optimize the standard operating procedures (SOP) for each instrument and to assure the quality of every procedure.During the first year after the establishment of the GMRCL at the CGMH, we tested and adopted procedures that were satisfactory for our purposes. These procedures included: replication of bacterial stocks, amplification of human DNA clones, annotation of each DNA clone, production of cDNA microarrays, validation of RNA quality and quantity, labeling of target specimens, competitive hybridization, scanning of slides, data analysis, and post-microarray validation of results. We present a summarization of the materials and procedures used at the GMRCL and discuss the reasons for using them.The information about the cDNA microarray analysis system at the GMRCL is compliant with the minimal information about a microarray experiment (MIAME) format. The information may be useful to both the investigators who are using this core facility and researchers at other institutes, who will establish their own in-house cDNA microarray systems.

Summary Salmonella enterica serotype choleraesuis ( S choleraesuis ) usually causes systemic infections in man that need antimicrobial treatment. We isolated a strain of S choleraesuis that was resistant to ceftriaxone and ciprofloxacin from a patient with sepsis. Ciprofloxacin resistance was associated with mutations in gyrA and parC , whereas the ampC gene ( bla CMY-2 ), responsible for ceftriaxone resistance, was carried by a transposon-like mobile element. This element was found inserted into finQ of a potentially transmissible 140 kb plasmid, with an 8 bp direct repeat flanking the junction regions. The appearance of this resistant S choleraesuis is a serious threat to public health, and thus constant surveillance is warranted.

Atrial fibrillation (AF) is the most common cardiac arrhythmia seen in clinical practice. The understanding of the pathophysiology of AF has changed drastically during the last several decades. Recent observations have challenged the concept of the multiple circuit reentry model in favor of single focus or single circuit reentry models. Atrial electrical dysfunction provides a favorable substrate and transmembrane ionic currents are key determinants. Interest has also been generated in the role of angiotensin converting enzyme (ACE) inhibition in reversing the electrical and structural remodeling. Reverting to the sinus rhythm seems to be the best way for reverse remodeling of atria during atrial fibrillation. Antiarrhythmic drugs (AADs) are only modestly effective. Of these amiodarone seems to provide the most benefits. Drugs like verapamil and ACE inhibitors may also help as adjuvant therapies in the reverse remodeling of atria. Nonpharmacological methods have been used to control both rate and rhythm for patients with AF. Recently, there has been a surge in interest to focal ablation of atrial foci. Focal sources of AF are commonly found in pulmonary veins (PV). Ablation in pulmonary veins through identification of the earliest endocardial activation has met with variable success. Anatomical approaches have involved circumferential radiofrequency ablation of pulmonary vein ostia using novel techniques such as balloon based circumferential ultrasound ablation system and circular cryoablation catheter. Most recently the segmental approach is preferred because the myocardial fibers surrounding the PV are not continuous. Segments where musculature is present can be identified using high frequency depolarization signals recorded through multi-electrode loop catheter or even conventional catheters.

Background: The effect of percutaneous transluminal angioplasty (PTA) in the treatment of hemodialysis vascular access stenosis is attenuated by a high restenosis rate, which results mainly from neointimal hyperplasia. Cellular proliferation is one of the most important biological mechanisms involved in neointimal hyperplasia and may be a potential target of intervention to prevent restenosis. Methods: We investigated the activity of cellular proliferation of restenotic lesions by means of immunohistochemistry, using an antibody to the proliferating cell nuclear antigen. Specimens from 10 primary stenotic and 20 restenotic lesions of 30 Brescia-Cimino fistulae were obtained during revision. Results: The proliferation index of the restenotic group was strikingly significantly greater than that of the primary stenotic group (intima, P P = 0.001). Proliferation indices of patients with diabetes in the restenotic group were significantly higher than those of patients without diabetes (intima, P = 0.028; media, P = 0.002). In the restenotic group, proliferation indices correlated negatively with the interval from PTA to restenosis (intima, r = −0.741; P r = −0.589; P = 0.006) and positively with the number of PTAs per lesion (intima, r = 0.754; P r = 0.506; P = 0.004). Conclusion: We show markedly high cellular proliferation activity in early restenotic lesions of arteriovenous fistulae. These findings indicate that adjunctive antiproliferative therapy is mandatory in preventing restenosis after PTA, especially in patients with diabetes.

Cardiac hamartomas are very rare and are demarcated masses of enlarged, hypertrophied, mature myocytes and collagen tissue. Cardiac hamartomas are generally circumscribed in the right ventricle or atrium, but not reported in the crista terminalis (CRT). The CRT is crucial in electrophysiology, is related to arrhythmogenesis, and is targeted by radiofrequency catheter procedures. Previous works only described the benign natures of prominent CRT using non-invasive methods. This study describes an unusual cardiac hamartoma originating from the CRT and extending toward the tricuspid valve. Microscopically, this hamartoma comprised dense collagen and adipose tissue, mixed with hypertrophy, but with disarrayed cardiomyocytes. An irregular gap junction, connexin43, was demonstrated in this cardiac hamartoma.

This study was aimed to ascertain the effect of sleep deprivation on subsequent cerebral ischemia in the rat hippocampal formation. Seven days after transient global cerebral ischemia induced by four-vessel occlusion method, most of the pyramidal cells in the hippocampal CA1 subfield underwent disruption and pyknosis as detected by cresyl violet staining. With OX-42, OX-18, OX-6 and ED1 immunohistochemistry, robust microglia/macrophage reactions were observed in the CA1 and dentate hilus. The majority of reactive microglia was rod-shaped, bushy or amoeboidic cells bearing hypertrophic processes. Astrocytes also displayed hypertrophic processes, whose immunostaining for glial fibrillary acidic protein was markedly enhanced. The ischemia-induced neuronal damage and glial reactions, however, were noticeably attenuated in rats subjected to pretreatment with sleep deprivation for five consecutive days. The most drastic effect was the diminution of OX-18, OX-6 and ED1 immunoreactivities, suggesting that the immune potentiality and/or phagocytosis of these cells was suppressed by prolonged sleep deprivation prior to ischemic insult. It is postulated that sleep deprivation may have a preconditioning influence on subsequent lethal cerebral ischemia. Hence, sleep deprivation may be considered as a therapeutic strategy in brain ischemic damage.