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The cell-free system for biosynthesis of proteins is becoming an important tool for protein engineering. In particular, introduction of the unnatural amino acids is achieved though cell-free protein synthesis with the use of chemically acylated tRNA that recognizes a specific codon. In the original method, however, it was difficult to control the system through changing tRNA composition, as the endogenous tRNAs are involved in the reaction. Thus, in the present study, we digested the tRNA within Escherichia coli S30 extract with resin-bound RNase A, and estimated the protein synthesis activity. It was revealed that this digestion process does not damage the activity, if a protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), is present in the digestion reaction.

Management of acute viral myocarditis is still controversial. Amrinone, a noncatecholamine nonglycoside bipyridine agent, produces sustained improvement of cardiac function and symptomatology in congestive heart failure (CHF). Amrinone demonstrates phosphodiesterase inhibitory activity that is relatively selective for the major phosphodiesterase isozyme in cardiac muscles, PDE III, which specifically hydrolyzes cyclic 3'5' adenosine monophosphate (cAMP). We investigated the effects of amrinone in an animal model of acute CHF related to myocarditis caused by the encephalomyocarditis virus (EMCV). Female C3H mice were inoculated intraperitoneally (i.p.) with 500 plaque-forming units of EMCV in 0.1 ml of saline. A total of 96 mice were randomly assigned to four groups. Each animal was administered 0.2 ml of phosphate-buffered saline (PBS) containing amrinone at a concentration of 1, 10, or 50 mg/kg, or PBS as an infected control, injected i.p. once daily for 21 days, starting on day 1 after viral inoculation. Each group contains 20 to 30 mice. Infected untreated mice survived at 80% (n = 16), however, only 13% (n = 16) of mice treated with amrinone (50 mg/kg) survived (p0.01). Downregulation of cardiac cAMP occurred 1 day after the viral infection. Although amrinone (10 and 50 mg/kg) treatment significantly (p0.05) increased the cardiac cAMP content and the dose of 10 mg/kg could potentially retard death from CHF due to viral myocarditis. The higher (50 mg/kg) doses of amrinone may produce unfavorable effects when used to treat mammals with viral myocarditis and CHF.

An activated partial thromboplastin time (APTT) based method was developed to determine the anticoagulant response in patient plasma to added purified activated protein C (APC). On the other hand, Bertina et al. (1994) reported that one point mutation of amino acid 506 in the factor V was observed in such APC resistance patients. APC resistance for blood samples with known abnormal findings on the coagulation test also may be determined. Coagmaster II for the APTT assay system (Sankyo, Tokyo, Japan) was employed. The APC resistance assay system was a useful reagent as a screening test for lupus anticoagulant (LA), in addition to APC resistance.

Strains of methicillin-resistant Staphylococcus aureus (MRSA) are potential pathogens in patients undergoing major surgery and in patients who are immunocompromised. Some MRSA produce a viscous extracellular slime that may interfere with immune function. In this study, slime formation by MRSA was examined in cases of nosocomial infection by this pathogen at a single hospital. The antibacterial resistance, phage and enterotoxin characteristics of strains isolated from patients with fatal infections were determined. MRSA strains were classified as those associated with fatal infection; causing progressive infection; causing superficial infection; and those isolated from the nasal cavity of the health-care professionals as a control group. The incidence of slime formation was highest in the MRSA associated with fatal infection. The incidence of slime formation in the control group was significantly lower than that in the other groups. Results suggest that slime formation by MRSA may be associated with a more severe infection. Rapid identification of slime-forming MRSA may facilitate the initiation of appropriate treatment and improve the patient's prognosis.

We report the unusual case of an 87-year-old woman with cardiac myxoma and adenomatous goiter. She exhibited slight elevations of serum interleukin-6 (IL-6), but levels of thyroid hormones such as T3, free T3 and free T4 were all abnormally low. Interleukin-6 may potentiate the alteration of thyroid metabolism.

Purpose: Here we have evaluated the effect of an atherosclerosis-related gene on dyslipidemia with the aim of preventing the onset of atherosclerosis. Methods: We performed medical examination on the inhabitants of Goto city from July 2005 to June 2010 under the Goto city sponsorship, and 3,151 inhabitants, who provided informed consent, agreed to continue participating in the study. We divided the participants into groups as per their age and performed a comparative analysis; we collected and analyzed blood samples to determine the association between single nucleotide polymorphisms (SNPs) of 4 genes (MTHFR, Adiponectin, HDAC4, and CARKL) and lipid (Tchol, LDL, TG, HDL) levels. Results: In case of an SNP in the MTHER gene, Tchol and LDL levels were higher in the CC group (in men aged 65 y) than in the TT group (Tchol: CC vs TT, 197.6±34.0 vs 176.5±36.1; p = 0.0143; LDL: CC vs TT, 117.5±30.8 vs 97.6±30.5; p = 0.0115). TG levels were lower in the CC group (in women aged 65 y or older) than in TT group (CC vs TT, 119.5±60.9 vs 148.0±10.2; p = 0.0096), and HDL levels were higher in the CC group than in the TT group (CC vs TT, 59.4±15.9 vs 55.7±15.5; p = 0.0063). In case of SNP in the Adiponectin gene, TG and LDL levels were higher in the TT group (in men aged 65 y or older) than in the GG/GT group, and HDL levels were lower in the TT group than in the GG/GT group (TG: TT vs GG/GT, 137.6±75.7 vs 107.2±67.8; p = 0.0329; LDL: TT vs GG/GT, 133.7±35.6 vs 111.2±30.78; p = 0.0195; and HDL: TT vs GG/GT, 48.0±10.4 vs 56.1±16.3; p = 0.0390) In case of SNPs in the HDAC4 and CARKL genes, there were no significant differences in the lipid levels between the groups. Conclusions: The results show that healthy life expectancy in elderly individuals can be predicted by analyzing the genes with respect to fat metabolism and determining the SNPS associated with the onset of atherosclerosis.

To investigate the pathogenesis of hepatic osteodystrophy (HOD) in parenchymal liver disease, we developed a laboratory model in animals using carbon tetrachloride (CCl4) and thioacetamide. Biochemical and histological parameters in the model were measured. In rats with both chronic non-cirrhotic liver injury and CCl4-induced cirrhosis, tibial bone volume was significantly lower than in controls. In CCl4-treated cirrhotic rats, the osteoid volume decreased while the urinary calcium/creatinine ratio increased. In all CCl4-treated rats, bone volume was significantly correlated with both the serum albumin concentration and the number of goblet cells reflecting intestinal villous atrophy. The serum concentration of vitamin D metabolites was not correlated with bone volume. Whole body retention of 47Ca was significantly lower in CCl4-treated cirrhotic rats than in controls. Furthermore, the bone volume in thioacetamide-treated cirrhotic rats was significantly lower than in controls. These data demonstrate that chronic parenchymal liver injury itself causes osteoporosis (i.e. HOD) due to a combination of low bone formation rates and high resorption rates, that HOD begins at the stage of chronic non-cirrhotic liver injury, that bone volume in HOD parallels liver damage and that the principal pathogenesis of HOD seems to be intestinal Ca malabsorption due to lower serum albumin and villous atrophy, while serum levels of vitamin D metabolites have little influence on the pathogenesis of HOD.

The efficacy of the combination of artemether with doxycycline or azithromycin was evaluated in 60 patients with acute uncomplicated falciparum malaria who attended malaria clinic in Mae Sot, Tak Province (Thai-Myanmar border). Patients (30 each) were randomized to receive (a) 300 mg artemether together with 100 mg doxycycline as initial doses, followed by 100 mg artemether plus 100 mg doxycycline at 12 hours later, then 100 mg doxycycline every 12 hours for another 4 days, or (b) 300 mg artemether together with 500 mg azithromycin, followed by 250 mg azithromycin at 24 and 48 hours. The follow-up period was 28 days. Patients in either group had a rapid initial response to treatment with comparable PCT and FCT. The cure rate of artemether-azithromycin regimen was significantly lower than that of artemether-doxycycline regimen (14.8 vs 53.3%). Low cure rate from artemether-azithromycin combination in this study was likely to be due to inadequate azithromycin dosage. However, with the low incidence of gastrointestinal adverse effects, the once daily dose of azithromycin could still be increased in order to enhance its clinical efficacy. The simplicity of drug administration and lesser incidence of adverse effects make azithromycin a more proper partner of artemether than doxycycline. Further dose-finding and pharmacokinetic study with the artemether-azithromycin combination is encouraging.

The efficacy and safety of sulbactam/cefoperazone (SBT/CPZ) were evaluated in 42 patients with respiratory tract infections, including pneumonia (29 patients) and lower respiratory tract infections (5 patients). Overall clinical efficacy rates (excellent + good) were 79% in pneumonia and 80% in respiratory tract infections in 34 patients evaluated for clinical efficacy. It was excellent that the clinical efficacy rate was 92% in mild and moderate pneumonia. Pathogens isolated from sputa were 31 strains, including 8 strains of Pseudomonas aeruginosa, 7 of Streptococcus pneumoniae, 3 of Staphylococcus aureus and 3 of Haemophilus influenzae. Since the isolates were eradicated in 18 strains, replaced in 3, unchanged in 2 and unknown in 8, the overall eradication rate was 91%. The eradication rates were 89% in beta-lactamase producing strains and 100% in beta-lactamase positive sputum, and excellent or good in 19 (83%) of 23 patients with beta-lactamase negative sputum. The eradication rate was 88% in 5 patients with beta-lactamase positive sputum. One patient experienced a moderate rash. Abnormal laboratory test values were observed in 10 patients (26.3%), but these abnormalities were mild and transient. These results suggested that SBT/CPZ was effective and safe for the treatment of respiratory tract infections caused by beta-lactamase producing as well as beta-lactamase non-producing bacteria.

Sulfoglucuronosyl paragloboside (SGPG) is a member of the sulfated glucuronic acid-containing glycolipid (SGGL) family found primarily in peripheral nerves. These glycolipids contain the HNK-1 carbohydrate epitope and are recognized by monoclonal IgM from patients with chronic demyelinating neuropathy and paraproteinemia. Recent studies indicate that SGGLs may serve as ligands for selectins, amphoterin, and laminin, suggesting that these glycolipids may play an important role in cellular adhesion. To elucidate the biological function of these glycolipids, we produced a murine monoclonal antibody (mAb) and studied its antigenic specificity. Using an enzyme-linked immunosorbent assay (ELISA), we found that the mAb designated as NGR50 belonged to the IgG2a subclass, and that the minimal titer (2 SD above the mean optical density value of control) of this mAb was 1:640, with 20 ng of purified SGPG as the antigen. Thin-layer chromatography (TLC) immunoblotting revealed that this mAb reacted specifically with SGPG and sulfoglucuronosyl lactosaminyl paragloboside (SGLPG), which is a structural analogue of the former, but not with other glycolipids. Desulfated derivates of SGPG and SGLPG did not react with mAb NGR50. Western blot analysis showed crossreactivity with human myelin-associated glycoprotein (MAG), but not with rat MAG or rat glycoprotein P0. Unlike anti-HNK-1 monoclonal antibody, however, NGR50 reacted only weakly with several proteins in the 20-30-kD regions, including human P0, suggesting that mAb50 has a different fine specificity as an anti-HNK-1 antibody. Immunocytochemical study of rat sciatic nerve using mAb NGR50 revealed positive staining at the outer surface of the myelin sheath and Schwann cells, as well as in the intervening connective tissues. Faint staining was also visible at the axolemmal-myelin interface; however, compact myelin was not stained.

We inquired whether the type of diabetic glomerulosclerosis, diffuse or nodular, is of value as an alternative to microalbuminuria in predicting later progression of renal disease. To answer this question, we conducted a retrospective cohort study in eleven Japanese non-insulin-dependent diabetes mellitus patients with normo- to microalbuminuria. Nodular diabetic glomerulosclerosis was found in six patients, and diffuse diabetic glomerulosclerosis in five patients. The mean follow-up period was 41.5 months (range 12-65). Three patients developed persistent proteinuria and one developed chronic renal failure. Mean level of serum creatinine in all patients was elevated from 0.97 +/- 0.23 mg/dl (SD) to 1.10 +/- 0.37 mg/dl (P = 0.098). The rate of increase in serum creatinine was 0.068 +/- 0.115 mg/dl/year in nodular diabetic glomerulosclerosis, and 0.023 +/- 0.069 mg/dl/year in a diffuse one. No difference was found between these two types of diabetic glomerulosclerosis (P = 0.445). We conclude that in normo- to microalbuminuria diabetic nephropathy the type of diabetic glomerulosclerosis, diffuse or nodular, is not necessarily an alternative to microalbuminuria in predicting its later progression in Japanese non-insulin-dependent diabetes mellitus patients.

We investigated the effect of amiloride, a Na(+)-H+ exchange blocker, on ventricular hypertrophy in a murine model of dilated cardiomyopathy (DCM). Mice with DCM were given orally amiloride for 60 days. The ratio of heart weight to body weight and left ventricular cavity dimension were significantly smaller in both amiloride groups than those in furosemide and control (untreated DCM) groups (p0.05). The fiber diameter was significantly smaller in amiloride groups than that in furosemide group (p0.01). Plasma and cardiac angiotensin II (AII) levels were decreased in amiloride-treated groups compared with those in furosemide or control group (p0.05). Our findings suggest that amiloride prevents the development of myocardial hypertrophy and left ventricular dilatation in DCM in association with a reduction of AII.

Antibodies against sulfoglucuronosyl glycosphingolipids (SGGLs) are known to be present in sera of patients with chronic polyneuropathy associated with IgM paraproteinemia. We recently studied rats sensitized with sulfoglucuronosyl paragloboside (SGPG), a major SGGL species, emulsified with keyhold limpet hemocyanin and Freund's adjuvant. The titer of the IgM class antibodies against SGPG increased up to 1:1,600, while that of the IgG class increased up to 1:800 2 weeks after sensitization. The antibodies showed a high degree of antigenic specificity; no cross-reactivity with other brain glycolipids could be detected. They, however, reacted with human myelin-associated glycoprotein (MAG) by Western blot analysis, but not with rat MAG. These animal models showed minor but clear clinical signs of neuropathy, consisting of mild tail muscle tone loss and walking disabilities. Electrophysiological examination of the sciatic nerves revealed nerve conduction abnormalities which consisted of conduction block and mild decrease in conduction velocity. Thus, our results support the concept that anti-SGPG antibodies may play an important pathogenetic role in this type of chronic neuropathy.

In vitro susceptibility and clinical response of multidrug resistant Plasmodium falciparum to the combination artemether-pyrimethamine were evaluated in patients with acute uncomplicated falciparum malaria. Sixty patients were randomized to receive 3 oral regimens of the combination artemether-pyrimethamine as follows: Regimen-I: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then placebo on the two consecutive days; Regimen-II: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then artemether (150 mg) plus pyrimethamine (50 mg) on the second day, and placebo on the third day; Regimen-III: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then artemether (150 mg) plus pyrimethamine (50 mg) on the second and third days. All patients had a rapid initial response to treatments with 95% of parasitemia being cleared within the first 24 hours. PCT24hours and PCT48hours were similar among the three drug regimens (11 vs 4, 6 vs 12, and 9 vs 11 patients for a 1-day, 2-day, and 3-day combination regimen, respectively). Fever was cleared within 48 hours in all patients in either group. Transient mild nausea, vomiting and loss of appetite were found in a few patients during the first 2 days of treatment. Seven patients did not complete the 28 day follow-up period (5 vs 2 in a 1-day vs 2-day regimen), the reason for withdrawal was not associated with drug-related adverse effects. Only 53 patients were therefore qualified for the efficacy assessment. There was 15, 13 and 5 patients in a 1-day, 2-day and 3-day combination regimens, respectively, who had reappearance of the parasitemia between days 11 and 21. The cure rates of the 3 treatment groups were statistically significantly different (0, 27.8, and 75% for a 1-day, 2-day and 3-day combination regimen, respectively). Two patients developed P. vivax malaria on days 20 and 24. All of the isolates were highly resistant to pyrimethamine, with MIC of 10(-5) M. There is potential advantage of this combination therapy in reducing the dosage and treatment period of artemisinin derivative, which is therefore likely to improve complaince in clinical practice. The use of a 3-day combination regimen (300 mg artemether plus 100 mg pyrimethamine on the first day, then 150 mg artemether plus 50 mg pyrimethamine on the second and third days) seems to be a good alternative regimen to sulfadoxine/ pyrimethamine in areas where P. falciparum is sensitive to pyrimethamine eg in Africa.

We report an autopsy case of a central nervous system (CNS) B-cell type lymphoma followed by cardiac tamponade. In this case, lymphoma cells which occurred primarily in the pericardium appear to metastasize to the brain and gradually increase in size in spite of control of the CNS lesion. The serum carbohydrate antigen 125 (CA 125) level was highly elevated and the autopsy findings showed the involvement of lymphoma only in the pericardium rather than the CNS, and the pericardium, not the tumor cells, was immunohistochemically positive for CA 125. Through this rare case, two things are suggested: first, the serum CA 125 level is elevated when B-cell type lymphoma infiltrates the coelomic epithelium; second, CA 125 is overproduced and secreted by the pericardium but not the lymphoma cells. Measurement of the serum CA 125 level may become a diagnostic marker for the infiltration of malignant lymphoma in the coelomic epithelium such as the pericardium, peritoneum or pleura.

We encountered a 78-year-old female with jaundice induced by Lutembacher's syndrome, which, to our knowledge, is the first such case to be reported. Laboratory data and ultrasonographic examination revealed liver congestion with dilatation of the inferior vena cava and hepatic veins. A large atrial septal defect was found using two-dimensional echocardiography; the mitral valve area measured 1.6 cm2 by planimeter. Clinicians should be aware of congenital heart disease as an underlying cause of jaundice.

This study was designed to evaluate the effects of amlodipine, a new calcium channel blocker, on the development of right ventricular hypertrophy and thickening of the media of the pulmonary arteries in a rat model of pulmonary hypertension. Pulmonary hypertension was induced in rats by administering a single injection of monocrotaline, 80 mg/kg. The oral administration of amlodipine, 3, 10, or 30 mg/kg/day, was initiated 24 hours later (day 1). On day 28 of therapy, we determined the right ventricular systolic pressure (RVSP), the mass ratio of the right ventricle (RV) to the left ventricle, the thickness of the wall of the RV, the diameter of myocardial fibers in the RV, the percent thickness of the media of the pulmonary artery, and the percent area of smooth muscle in the pulmonary arteries. The magnitude of all parameters was significantly less in the rats administered amlodipine, 30 mg/kg/day, vs. the control group given monocrotaline alone. RVSP, the percent medial thickness, and the percent smooth muscle area, were significantly lower in rats administered a dose of amlodipine, 30 mg/kg/day vs. 10 mg/kg/day. The oral administration of amlodipine, 30 mg/kg/day, inhibited the development of RV hypertrophy and medial thickening of the pulmonary arteries in rats exposed to monocrotaline significantly more effectively vs. the untreated control exposed only to monocrotaline.

We have observed the emission spectra in collisions of bare and hydrogen-like C and O ions with helium atoms and hydrogen molecules as target gases in the soft X-ray region using a window-less Si(Li) detector at collision energies around 100 keV. Because it is found that the 1s-2p emission is dominant in each spectrum, we indicate that the cascade from the upper states give the large population of the 2p state after the consideration using state-selective capture cross sections calculated by the TC-AOCC method.

Treatment of the pyridinium salts of heparin with N-methyltrimethylsilyl-trifluoroacetamide (MTSTFA) in pyridine for 2 h at various temperatures caused specific 6-O-desulfations from trisulfated disaccharide units to various degrees without detectable depolymerization or other chemical changes. In order to assess the importance of 6-O-sulfate groups in N-sulfated glucosamine (GlcNS) residues to promote FGF-1 and FGF-2 activities, various 6-O-desulfated (6-O-DS-) heparins were quantitatively examined for activity as enhancers or inhibitors of specific FGF-1- and FGF-2-induced proliferation of BALB/c3T3 clone A31 (A31) cells and the chlorate-treated cells. The present results suggested that a high content of 6-O-sulfate groups in GlcNS residues was required for activation of FGF-1, but not FGF-2. However, complete 6-O-desulfation of trisulfated disaccharide units in heparin resulted in loss of the ability to activate FGF-2, although the desulfated product bound strongly to FGF-2.

The prognostic factor was identified by performing 123I-Metaiodobenzylguanidine (MIBG) myocardial scintigraphy on 17 patients with dilated cardiomyopathy (DCM). During 5 years period, 9 patients had cardiac events, four of whom died, six were admitted due to heart failure and five had ventricular tachycardiac events. At the starting point, we collected rest early and 3-hr-delayed MIBG SPECT along with rest 201T1 (T1) SPECT. In the SPECT, regional tracer uptake was scored using 4-grades defect score (0 = normal to 3 = uptake-defect), and summed up to total defect score (TDS). At the same time, we estimated left ventricular end-diastolic dimension/body surface area (LVDd/BSA), end-systolic dimension/body surface area (LVDs/BSA) and left ventricular ejection fraction (LVEF) by echo-cardiography, pulmonary arterial wedge pressure (PAWP) and New York Heart Association (NYHA) symptom class. We compared the clinical and hemodynamic parameters between the patients with cardiac events (group A) and the other patients (group B). TDS of delayed MIBG SPECT (p0.001), TDS of early MIBG SPECT (p0.05), TDS of T1 SPECT (p0.01), LVDd/BSA (p0.01), LVDs/BSA (p0.001) and NYHA class (p0.05) of group A were significantly larger than those of group B. But, LVEF of group A was significantly less than that of group B (p0.01). On multivariate analysis, the following parameters were independent predictors of cardiac events: TDS of delayed MIBG SPECT (p0.001), PAWP (p = 0.0124) and LVDd/BSA (p = 0.0026). These data suggest that delayed MIBG scintigraphy is thought to be important to predict cardiac events in patients with DCM.

We measured RNA and DNA concentrations in cultured chick embryonal retinal pigment epithelial cells to investigate the effects of dopa and oxygen on DNA and RNA synthesis. RNA/DNA ratios were decreased by addition of 250 microM dopa. Decrease of RNA/DNA ratios was suppressed when the oxygen concentrations were reduced from 20% to 10%. Incubation with medium containing 100 microM dopa increased RNA/DNA ratios in 10% oxygen. Exposure of retinal pigment epithelial cells to 250 microM dopa caused the decrease of RNA concentrations in the retinal pigment epithelial cells, which was ameliorated by lowering oxygen concentrations. However, the addition of 100 microM dopa in 10% oxygen stimulated retinal pigment epithelial cells and seemed to increase RNA concentrations.

The effects of combination therapy with the immunomodulators OK432 (derived from the Su strain of Streptococcus pyogenes A3; 1 unit corresponds to 0.1 mg of dried streptococci dissolved in 0.1 ml of saline) and human recombinant interferon-alpha A/D (IFN) on cardiac atrial natriuretic peptide (ANP) gene expression and myocardial hypertrophy were examined in a murine model of viral myocarditis with congestive heart failure. Therapy was started 24 h after inoculation with encephalomyocarditis virus and was continued for 14 days. The plasma ANP concentration in untreated infected mice was significantly (P.01) increased on day 10 (115 +/- 48 pg/ml) and day 30 (43 +/- 22 pg/ml) after inoculation relative to that in uninfected controls (5 +/- 4 pg/ml), whereas plasma ANP levels in treated mice were significantly (P.01) reduced on day 10 (14 +/- 13 pg/ml) and day 30 (11 +/- 9 pg/ml) in comparison with untreated infected mice. The atrial and ventricular ANP messenger RNA (mRNA) concentrations in untreated mice showed increases of approximately 1.4- and 29.3-fold, respectively, on day 10 and increases of 1.8- and 34-fold, respectively, on day 30 compared with the concentration in uninfected controls. Combined OK432 and IFN significantly (P.01) reduced the increase in ANP mRNA concentration in ventricles to 6.0- and 6.7-fold on days 10 and 30, respectively. Neither OK432 nor IFN monotherapy reduced the ANP mRNA concentrations in atria and ventricles compared with those in untreated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of interferon-alpha A/D (IFN) therapy in combination with various immunosuppressants were investigated in a murine model of viral myocarditis. Viral infection is an important cause of morbidity in immunocompromised hosts and transplant recipients. Human IFN therapy reduces viral replication, reducing the virus-induced myocardial destruction. Groups consisting of 25 C3H/He mice received i.p. injections of prednisolone, azathioprine, 15-deoxyspergualin, cyclosporine or tacrolimus (FK506), for 16 days beginning 2 days before inoculation with 500 plaque-forming units of encephalomyocarditis virus (EMCV). IFN, 10(4) U/g daily, was administered i.p. alone or in combination with immunosuppressants to separate groups of mice beginning on the day of viral inoculation. Animals were sacrificed at random at 4 or 10 days after inoculation with EMCV. The survival rate was significantly higher in mice treated with azathioprine, 15-deoxyspergualin, cyclosporine or FK506 in combination with IFN than in infected controls (P.01) and was similar to the rate in the IFN monotherapy group. Survival in mice treated with prednisolone resembled that in infected controls and was significantly lower than in mice treated with IFN (P.01). Heart weight was lower and cellular infiltration in the myocardium was reduced in mice treated with both FK506 and IFN compared with mice given IFN monotherapy. The results suggest that the effect of IFN therapy in viral myocarditis differs depending on which immunosuppressants is used. The findings suggest that the combination of FK506 and IFN may have beneficial effects in hosts with viral myocarditis by reducing cellular infiltration of heart.

We reported a case of myokymia with abnormal F response. A 60-year-old male with chronic alcoholism was admitted to our hospital with complaint of muscle cramp in both legs just after drinking. Neurological examination revealed muscle pain and weakness of the legs, absence of bilateral Achilles tendon reflexes and prominent myokymia in his right quadriceps femoris and left calf muscles. The electrophysiological examination showed reduced conduction velocity, high amplitude, increased number of phases and long duration of F responses suggesting increased excitability of motoneuron pool. The epidural nerve block brought about a disappearance of the myokymia and an improvement of the abnormal features of F response. The myokymia gradually tended to be milder in the clinical course. The relationship between the myokymia and the abnormal F responses indicated that the increased excitability of spinal motoneurons might play an important role on the generation of myokymia of this patient.

The long-term effects of losartan, an angiotensin II subtype-I receptor antagonist, were compared with those of captopril in a murine model of dilated cardiomyopathy caused by encephalomyocarditis virus. Four weeks after viral inoculation, 42 DBA/2 mice were given oral losartan 1.2 mg/kg/day (n = 8), 12 mg/kg/day (n = 8) or 60 mg/kg/day (n = 8) or captopril 7.5 mg/kg/day (n = 8) in drinking water or distilled water (n = 10). Mice were killed at the end of the 12-wk treatment period. Heart weight, left ventricular thickness, left ventricular cavity dimension and myocardial fiber diameter were significantly lower in mice given losartan 60 mg/kg as compared with the infected untreated group. Captopril had a similar effect on all parameters. The pathologic score of cardiac fibrosis was significantly lower in the mice treated with captopril but was not reduced in the mice treated with losartan. Moreover, as compared with the age- and sex-matched normal mice, cardiac mass and myocardial fiber diameter were significantly lower in normal mice treated with losartan 60 mg/kg. This study suggests that long-term treatment with losartan may prevent thickening of left ventricular wall and cavity dimension in dilated cardiomyopathy caused by encephalomyocarditis virus. The potency, and perhaps the efficacy, of losartan appear to be less than those of captopril.

Mesenteric infarction and other acute ischaemic intestinal diseases are still a challenging diagnostic problem. Based on animal experiments, intestinal fatty acid binding protein (I-FABP), which is uniquely localised to the bowel, has recently been proposed as a new serum marker for intestinal ischaemia. This paper reports on two cases with acute intestinal ischaemic diseases, and the measurement of serum I-FABP by western blot analysis. The concentrations of ordinary serum markers were normal and the bowel necrosis was not diagnosed until surgical exploration. Immunochemical analysis showed that the I-FABP concentrations in the patients' serum samples were high at the time of admission, and that I-FABP was undetectable in the samples obtained after bowel resection and in healthy control subjects. This paper suggests that I-FABP is released into the circulation in the acute phase of intestinal ischaemia and that I-FABP can be used in establishing the diagnosis of ischaemic intestinal diseases.

Ornithine decarboxylase (ODC,EC 4.1.1.7), a rate-limiting enzyme in polyamine biosynthesis, is known to be induced by a beta-adrenoceptor agonist, isoproterenol (ISO). ODC activity and cardiac polyamine content are considered to be correlated with ISO-induced cardiac hypertrophy in rat hearts. To determine whether ISO-induced cardiac ODC activity is mediated through the renin-angiotensin system, especially at the AT1-receptor, we used a nonpeptide AT1 receptor antagonist, losartan, in this study. Losartan (10 mg/kg) suppressed both heart ODC and polyamine contents in ISO-treated rats. Although metoprolol (a selective beta-adrenoceptor antagonist) totally suppressed ODC activity, these results suggest that ISO-stimulated cardiac ODC activity may be regulated through beta 2-adrenoceptors coupled with AT1 receptors in rats.

Various vector control measures were applied in different endemic areas in two provinces, Saraburi and Chanthaburi, with comparison among different control measures. Application of IGR (insect growth regurator, pyriproxyfen) was introduced at Wat Tam Pra Pothisat, Tab-Kwang District, Saraburi Province. Some integration measures were performed at villages 6 and 8, Patavee, Makham District, Chanthaburi Province. In Tab-Kwang District with low malaria endemicity at the study site predators were not able to be released due to rapid velocity of running water. IGR could effectively control malaria compared to the basin released predators. Another endemic areas villagers 6 and 8, Patavee, Makham, Chanthaburi Province was chosen. Highly endemic multidrug resistant malaria has been prevalent for many years in this area. Integration of Kanda's trapping system, application of IGR, use of both residual spraying and impregnated bed-net methods with etofenprox successfully interrupted malaria infection. The application of these methods as an integrated control system could be adjusted to environmental conditions. The results of this study suggest rapid effective vector control.

All signals of 1H- and 13C NMR spectra of oleandomycin and the esterolitic cleavage compound of oleandomycin, and all signals of 1H-NMR spectra of oleandomycin 2'-phosphate were determined using two-dimensional methods as 1H-1H and 13C-1H COSY NMR, and DEPT NMR in D2O solution. The two modified products of oleandomycin were prepared by two strains of Escherichia coli highly resistant to erythromycin. These results are basically useful in determination of the structure of novel metabolites of oleandomycin inactivated by bacterial action.

We evaluated the diagnostic value of 123I-metaiodobenzylguanidine (MIBG) and 123I-labeled beta-methyliodophenyl pentadecanoic acid (BMIPP) myocardial SPECTs for evaluating coronary artery disease and left ventricular function, in comparison with the diagnostic value of 201Tl (Tl) SPECT. For forty-nine patients with coronary artery disease, resting MIBG and BMIPP SPECTs were performed to detect coronary artery stenosis, compared with the diagnostic value of exercise Tl. Left ventricular ejection fraction and regional wall motion were compared with the total US (TUS) and regional US (RUS) of resting MIBG and BMIPP SPECTs, and in turn, compared with resting Tl SPECT. The sensitivity of resting BMIPP SPECT for detecting coronary artery stenosis was lower, and the specificity of resting MIBG SPECT was lower than the other two methods. The accuracy of resting MIBG SPECT for evaluating coronary lesions was nearly the same as the accuracy of exercise Tl, but higher than that of BMIPP SPECT. Left ventricular ejection fraction was well correlated with TUS of resting MIBG SPECT (r = 0.80), resting BMIPP SPECT (r = 0.77), and resting Tl SPECT (r = 0.68). Regional wall motion was most correlated with RUS of resting BMIPP SPECT, compared with that of resting Tl and MIBG SPECTs. These data suggest that resting MIBG SPECT is useful for detecting coronary artery disease and that resting BMIPP SPECT is valuable in evaluating regional left ventricular function.

Enteroviral myocarditis is often a relatively benign condition in adults. Physicians, therefore, may not always record detailed clinical and laboratory data in such patients. As such, they may not recognize viral involvement in organs beyond the heart. The purpose of this study was to examine the hepatic involvement of enteroviral peri-myocarditis and to compare the other diseases with congestive heart failure. We analyzed 18 patients (ages 15-64) who were diagnosed as having enteroviral myocarditis (n = 16) or pericarditis (n = 2). Serology was positive for coxsackie viruses in 11 patients and echoviruses in six patients. A diagnosis of hepatic involvement was made by the following laboratory data: rising levels of alanine amino transferase (ALT), aspartate amino transferase (AST) and exceeded serum ALT compared with AST levels. A ratio of ALT/AST more than 1.0 was greatly frequent in patients with peri-myocarditis (72%; 13/18) compared with acute myocardial infarction (0%; 0/10) and idiopathic dilated cardiomyopathy (3%; 3/10). In summary, hepatic involvement in the setting of acute enteroviral peri-myocarditis may be considerably more common in adults than previously suspected. The recognition of hepatic involvement in association with enteroviral peri-myocarditis may allow improvement of diagnostic sensitivity and alter approaches to treatments of acute viral myocarditis.

Atrial natriuretic peptide (ANP) may be an important factor in myocardial infarction and subsequent congestive heart failure. In the failing heart, ANP is expressed in both the atrium and the ventricle. ANP has now been localized with 125I-labeled monoclonal antibodies (MAbs) in vivo in a rat model of myocardial infarction. Myocardial infarction was produced in 3-month-old Wistar rats by ligating the left anterior coronary artery. Two MAbs to rat alpha-ANP accumulated in the infarcted left ventricles of treated rats to a significantly greater extent (p0.01) than in the noninfarcted left ventricles of control rats. However, an irrelevant MAb also accumulated to a significantly greater extent in infarcted myocardium than in control myocardium. Thus, the accumulation of the two MAbs to ANP in infarcted tissue seems to be nonspecific and may be due to increased permeability of the injured myocardium.

The increasingly long survival of cancer patients raises the question whether there might be an association between myocardial infarction (MI) and different types of cancer, especially since these different diseases share some of the same risk factors, like smoking. We describe a retrospective study in which we examined the autopsied hearts of 1642 cancer patients to determine the incidence of MI in different types of cancer and then studied the records of 106 of these cancer patients with complicated of fatal MI to determine their risk factors. The incidence of MI among the 1642 cancer patients was 6.5%. It was significantly higher in patients with squamous cell type cancers of the lung, head and neck, and urothelial tract cancer as compared with other types of cancers. The major coronary artery disease (CAD) risk factors in these patients were smoking, hypertension and left ventricular hypertrophy. Before therapy begins, cancer patients, especially those with squamous-cell-type cancer, should be screened for CAD risk factors, such as smoking, hypertension and left ventricular hypertrophy, and treated accordingly.

We determined the serum concentration of interleukin-8 (IL-8) in patients with chronic sarcoidosis and assessed its value as a marker of disease activity. The serum concentrations of IL-8 and tumor necrosis factor-alpha (TNF-alpha) were determined by enzyme-linked immunosorbent assays. Serum angiotensin-converting enzyme (ACE) activity was measured by a colorimetric assay in 16 patients with chronic sarcoidosis. Thirteen of the 16 patients with chronic sarcoidosis showed a serum IL-8 concentration higher than the normal range. The mean (+/- S. E.) serum IL-8 concentration in patients with active sarcoidosis (n = 6) was 18.7 +/- 1.3 pg/mL and that in patients with inactive sarcoidosis (n = 10) was 8.0 +/- 1.1 pg/mL; the difference was statistically significant (p = 0.002). An overall positive correlation between serum IL-8 concentration and serum ACE activity was apparent; however, only four of the 16 patients with sarcoidosis had a serum ACE activity greater than the normal range. TNF-alpha was detected in the serum of only two patients. The serum concentration of IL-8 may prove a useful marker for monitoring disease activity in sarcoidosis, especially in the chronic stage.

First, we longitudinally analyzed 177 cerebral-palsied children (CP) who were born in Kyoto City between 1977 and 1985. They were all visited St. Joseph Hospital for Crippled Children in Kyoto during the period 1977 to 1991 in order to investigate the relationship between the prognosis of perinatal care and the changing panorama of CP in Kyoto. The average occurrence rate of CP per 1,000 live birth during the 9 years in Kyoto was 1.12. 177 CP were divided into 3 groups according to their birth years: 1977-1979 (47 CP); 1980-1982 (62 CP); and 1983-1985 (68 CP). Then we compared the distribution of birthweights and gestational periods among the 3 groups. We found a significant increasing trend in the percentage of CP in babies with birthweight less than 2,000 g. Second, we examined 162 CP; 15 born outside of Kyoto were excluded because of extraneous influences of perinatal care. 162 were divided into 3 groups according to their birth years: 1977-1979 (44); 1980-1982 (56); and 1983-1985 (62). We also compared the risk factors and prognosis according to the birthweights and gestational ages among the 3 groups. This study revealed a decreasing trend in the frequency of convulsions of full term CP, dyspnea and oxygen administration of premature CP in the neonatal period. At the same time, the motor development of CP without mental retardation had improved significantly in the later period. However, in the last 3 years the distribution of the severity of motor disturbance at 4 years of age among CP with birthweight of 1,000-2,000 g was either mild or severe.(ABSTRACT TRUNCATED AT 250 WORDS)

A new side effect of interferon (IFN) therapy, glucose intolerance was investigated using insulin-clamp study. In 75 g oral glucose tolerance tests before and after the IFN therapy showed no significant difference, whereas clamp study showed a significant decrease of glucose disposal. Our data suggested that insulin resistance was the main reason for glucose intolerance observed during INF therapy in the patients with chronic active hepatitis C. Early detection and strict control of glucose intolerance could avoid the progress of glucose intolerance.

Since a number of anti-glycosphingolipid (GSL) antibody activities have been demonstrated in patients with various neurological disorders, the presence of common antigens between brain microvascular endothelial cells (BMECs) and the nervous tissues presents a potential mechanism for the penetration of macromolecules from the circulation to the nervous system parenchyma. We first investigated GSL composition of cultured bovine BMECs. Bovine BMECs express GM3(NeuAc) and GM3(NeuGc) as the major gangliosides, and GM1, GD1a, GD1b, GT1b, as well as sialyl paragloboside and sialyl lactosaminylparagloboside as the minor species. Sulfoglucuronosyl paragloboside was also found to be a component of the BMEC acidic GSL fraction, but its concentration was lower in older cultures. On the other hand, the amounts of neutral GSLs were extremely low, consisting primarily of glucosylceramide. In addition, we analyzed the effect of anti-SGPG IgM antibody obtained from a patient of demyelinative polyneuropathy with macroglobulinemia against cultured BMECs. Permeability studies utilizing cocultured BMEC monolayers and rat astrocytes revealed that the antibody facilitated the leakage of [carboxy-14C]-inulin and 125I-labeled human IgM through BMEC monolayers. A direct cytotoxicity of this antibody against BMECs was also shown by a leakage study using [51Cr]-incorporated BMECs. This cytotoxicity depended on the concentration of the IgM antibody, and was almost completely blocked by preincubation with the pure antigen, sulfoglucuronosyl paragloboside. Our present study strongly supports the concept that immunological insults against BMECs induce the destruction or malfunction of the blood-nerve barrier, resulting in the penetration of the immunoglobulin molecule to attach peripheral nerve parenchyma.

We presented a 65-year-old man with the right occipital dural arteriovenous malformation (AVM) who first experienced photopsia in his left inferior quadrantanopic field and then developed formed hallucinations 8 days later. His visual hallucinations disappeared with saccadic eye movements. EEG showed no epileptic discharge. MRI revealed hyperintensity in the right medial occipital lobe on proton density image. 123I-IMP SPECT during the hallucinations revealed decrease of regional cerebral blood flow (r-CBF) not only in the right medial occipital lobe but also in the right lateral occipital and in the right medial temporal lobe. Both left inferior quadrantanopia and visual hallucinations disappeared following the treatment of the dural AVM by transarterial embolizations. Because the lesion on MRI improved after the treatment, we considered that the lesion was brain edema, not infarction. Additionally decreased r-CBF in the temporo-occipital lesion on SPECT improved after the treatment, we emphasized the role of the temporo-occipital lesion as the cause of visual hallucinations in the hemianopic field.

A 56-year-old Japanese male patient with Down's syndrome was bitten by a hepatitis B envelope antigen (HBeAg) carrier and become an asymptomatic HBeAg carrier without seroconversion. His mitogen response of T cells was poor compared with that of healthy controls. An impaired T cell response to hepatitis B virus infection may be responsible for the HBeAg carrier with Down's syndrome.

Giant magnetoresistance effect and structural properties of NiFeCo/Cu multilayers deposited by an rf magnetron sputtering method on glass substrates with Fe, NiFeCo, Cr and Zr buffer layers have been investigated. For all the buffer layers, the multilayers showed magnetoresistance which oscillated as a function of Cu layer thickness. The Fe and Cr buffered multilayers showed stronger antiferromagnetic coupling than the NiFeCo and Zr buffered ones. All the multilayers except for the Fe buffered ones exhibited more or less (111) preferred orientation. The Zr buffered multilayers showed especially strong orientation, where the X-ray (111) peak intensity was 20 times as large as for the NiFeCo, Cr or nonbuffered multilayers.

Foix–Chavany–Marie syndrome (FCMS) is characterised clinically by automatic voluntary dissociation of orofacial motility. It is caused by bilateral anterior opercular lesions and its aetiology is heterogeneous.1 Clinically, most cases of FCMS can be divided into three categories— developmental , acute/subacute , and transient .2 The most common cause of the developmental form is congenital bilateral anterior opercular dysplasia. The acute/subacute form is usually caused by infection in the CNS or cerebrovascular disease. The underlying pathogenesis of transient form is epilepsy. Rare variant cases of FCMS presenting with a slowly progressive clinical course have also been reported.3 We describe the clinical features of a patient with adult onset, slowly progressive FCMS, thought to be associated with chronic herpes simplex encephalitis. A 29 year old Japanese woman developed epilepsy of generalised tonic-clonic type at the age of 15 and had been taking anticonvulsants for 14 years. She had had a normal pregnancy and delivery. Developmental assessment during schooling showed normal motor and psychological ability. At the age of 27, she presented with dysarthria and dysphagia, which deteriorated gradually during the following 18 months. She also had difficulty with fine movements of her right arm at the age of 29. On admission, her voluntary orofacial motility was disturbed bilaterally, while emotional and involuntary facial movements …