Search PubMed⌕ Search

Biomedical subjects

M Inada

Publications and source records attributed to M Inada.

At least 37 records · Page 2Linked to original sources
PubMed1995

Thyroid stimulating antibody in sera of Graves' ophthalmopathy patients as a possible marker for predicting the efficacy of methylprednisolone pulse therapy.

Nine patients with Graves' ophthalmopathy (GO) were treated with intravenous methylprednisolone pulse therapy and followed up by ophthalmological assessment, magnetic resonance imaging, and thyroid-associated autoantibody (thyroid stimulating antibody (TSAb), TSH binding inhibitor immunoglobulins (TBII), and anti-eye muscle antibody (EMAb)). Ophthalmological assessment was performed by the ophthalmopathy index (OI) which was made on the basis of the system recommended by the American Thyroid Association Committee. EMAb was expressed as the ratio of density of the 64 kDa band of eye muscle membrane to that of 92 kDa non-specific band found with all normal sera when assessed by western blotting. Five patients with mild ophthalmopathy (OI < 4) did not show progressive improvement in OI. Three of 4 patients with severe eye disease (OI > 4) showed a progressive and distinct improvement in OI. These 3 patients had high TSAb levels before methylprednisolone pulse therapy. One patient with severe ophthalmopathy did not respond to this pulse therapy; this patient's TSAb was negative. A significant positive correlation was observed between the activity of TSAb before treatment and the improvement in OI (delta OI) (r = 0.86, P < 0.01, n = 9). The relationship between delta OI and EMAb did not reach significance. These results suggest that TSAb in sera of GO patients can be a useful marker for predicting the efficacy of methylprednisolone pulse therapy.

Adolescent↗
PubMed1995

[Clinical significance of abnormal high signal intensity of left ventricular myocardium by gadolinium-diethylenetriaminepenta-acetic acid enhanced magnetic resonance imaging in hypertrophic cardiomyopathy].

The significance of abnormal high signal intensity observed in left ventricular myocardium by gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) enhanced magnetic resonance (MR) imaging in hypertrophic cardiomyopathy (HCM) patients was assessed by comparison with T1-weighted MR imaging, thallium-201 (201Tl) myocardial scintigraphy, radionuclide angiocardiography, M-mode echocardiography, electrocardiography, and chest radiography. The 16 patients were divided into three groups: 8 patients (group I) with abnormal high signal intensity before and after Gd-DTPA enhancement, 4 (group II) with abnormal high signal intensity only after enhancement and 4 (group III) without abnormal high signal intensity. Thallium-201 myocardial single photon emission computed tomography (SPECT) showed 4 of the 8 patients in group I, 3 of the 4 patients in group II and only 1 of the 4 patients in group III had abnormalities of regional 201Tl uptake in the left ventricular myocardium. No significant difference in left ventricular ejection fraction (LVEF) was seen between groups I, II, and III (64 +/- 13%, 67 +/- 17% and 71 +/- 7%, respectively) although three patients of group I had LVEF of less than 55%. Left ventricular peak filling rates (PFR) of groups I and II were significantly lower than that of group III (1.90 +/- 0.44, 2.41 +/- 0.43 and 3.37 +/- 0.48 EDV/sec, respectively). Group I had larger end-diastolic left ventricular dimension (LVDd), significantly larger end-systolic left ventricular dimension (LVDs), and smaller % fractional shortening (%FS) than group III (49 +/- 4 vs 42 +/- 6 mm, 31 +/- 5 vs 22 +/- 4 mm, and 38 +/- 8 vs 49 +/- 4%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Structural determinants of the action against Escherichia coli of a human inflammatory fluid phospholipase A2 in concert with polymorphonuclear leukocytes.

Extracellular 14-kDa phospholipases A2 (PLA2) in inflammatory exudates can contribute to bacterial phospholipid (PL) degradation during phagocytosis of Escherichia coli by polymorphonuclear leukocytes (PMN) and are highly active toward E. coli treated with the bactericidal/permeability-increasing protein (BPI) purified from PMN. PLA2 activity toward BPI-treated E. coli varies greatly among members of this conserved family of enzymes and apparently depends on a cluster of basic residues in a variable surface region near the NH2 terminus for recognition of this biological target (Weiss, J., Wright, G.W., Bekkers, A.C.A.P.A., van den Bergh, C.J., and Verheij, H.M. (1991) J. Biol. Chem. 266, 4162-4167). We have examined by site-specific mutagenesis of a recombinant PLA2 that is identical to an enzyme in human synovial fluid (containing His-6, Arg-7, Lys-10, and Lys-15 and a global net charge of +15) the role of basic residues in this region in PLA2 action against PLA-deficient (pldA-) E. coli. Substitution of Ser for Arg-7 +/- Gln for Lys-15 caused, respectively, about a 10- and 25-fold reduction in BPI-dependent PLA2 binding and activity to E. coli, but had no effect on hydrolysis of PL of autoclaved E. coli or dispersions of purified PL. PL degradation during phagocytosis was increased after pretreatment of E. coli (or PMN) with wild-type PLA2 followed by removal of unbound PLA2. Thus, the PLA2 binds to cells before phagocytosis followed by internalization of the enzyme along with E. coli and intracellular action. Mutant (e.g. R7S +/- K15Q) PLA2 show the same BPI-independent binding to E. coli as the wild-type enzyme but 10-30-fold reduced activity during phagocytosis, reflecting lower intracellular activity of these enzymes. Thus, structural determinants first implicated in PLA2 action toward E. coli treated with purified BPI apparently are also important in the intracellular action of PLA2 during phagocytosis by PMN.

Animals↗
PubMed1994

Determinants of the inhibitory action of purified 14-kDa phospholipases A2 on cell-free prothrombinase complex.

It has been suggested (Kini, R. R., and Evans, H. J. (1987) J. Biol. Chem. 262, 14402-14407) that the anticoagulant activity of members of the 14-kDa phospholipase A2 (PLA2) family depends on the presence of basic residues within a variable surface region (residues 54-77) distinct from both the conserved catalytic machinery and surface sites mediating the antibacterial action of these enzymes (see Weiss, J., Inada, M., Elsbach, P., and Crowl, R. M. (1994) J. Biol. Chem. 269, 26331-26337). To further define the determinants of the anticoagulant activity of PLA2, we have analyzed the inhibitory effects of purified native and recombinant PLA2 on cell-free prothrombinase. Both native and recombinant wild-type pig pancreas (net charge -1) and human "secretory" PLA2 (net charge +15) produced similar dose-dependent inhibition of prothrombinase activity that was significantly less potent than a toxic PLA2 purified from snake venom. Site-specific mutations that either increased or decreased PLA2 activity toward bactericidal/permeability-increasing protein-treated Escherichia coli by up to 50-fold had no effect on antiprothrombinase activity. In contrast, substitution of Arg for Asp-59/Gly for Ser-60 in the pig PLA2 increased antiprothrombinase activity by 5-10-fold without affecting catalytic activity toward a range of phospholipid substrates or antibacterial activity. Comparison of antiprothrombinase activity of catalytically active and inactive forms of the PLA2 and under a range of phospholipid conditions revealed that the potent antiprothrombinase activity of native toxic venom PLA2 and of the D59R.S60G mutant pancreatic PLA2 reflect combined catalytic and noncatalytic actions, the latter apparently dependent on basic residues at discrete surface sites in the enzyme.

Anticoagulants↗
PubMed1994

The effect of successful angioplasty on variables of signal-averaged electrocardiogram and ventricular wall motion in patients with a first myocardial infarction.

The correlation among three variables of late potentials (LPs) obtained by signal-averaged electrocardiography (SAECG) and improvement of ventricular wall motion estimated by echocardiography were studied in 66 patients with a first acute myocardial infarction (MI). Patients with bundle-branch block, intraventricular conduction delay, multi-vessel disease, previous MI, repeat percutaneous transluminal coronary angioplasty (PTCA), or evidence of reinfarction during a 6-month follow-up were excluded. A total of 66 patients was divided into two groups, with (Group 1: n = 27, age 56 +/- 11) or without (Group 2: n = 39, age 61 +/- 10) improvement of ventricular wall motion. Three variables of LPs and ventricular wall motion index (WMI) estimated and scored by echocardiography at admission (WMI 1) and at 6 months after MI (WMI 2) were compared in each group. In Group 1 (WMI 1 vs. WMI 2, p < 0.002), 20 of 27 patients underwent successful angioplasty; in Group 2 (WMI 1 vs. WMI 2, p = NS), 7 of 39 patients had successful emergency angioplasty. There were significant differences in three variables of LPs between the time of admission and at 6 months after MI in Group 1 but not in Group 2. Higher incidence of LPs and greater frequency of successful emergency PTCA were found in Group 1 compared with Group 2. These results suggest that because myocardial ischemia is reversed by successful angioplasty, ventricular wall motion is improved and the arrhythmogenic substrate that generates LPs is stabilized electrically. Stunned or hibernating myocardium may be the arrhythmogenic substrate that generates LPs.

Adult↗
PubMed1994

Alteration of glycosaminoglycans induced by cadmium in cultured vascular smooth muscle cells.

Alteration of glycosaminoglycans (GAGs) in cultured bovine aortic smooth muscle cells after exposure to cadmium was investigated. It was revealed that cadmium increased the accumulation of GAGs metabolically labeled with [3H]glucosamine but decreased that with [35S]sulfate in the cell fraction, the cell surface fraction and the medium fraction. This suggested that cadmium stimulated the biosynthesis of GAGs but inhibited their sulfation in the cells. A similar alteration was observed in cadmium-treated human aortic smooth muscle cell layer. Of tested cations including cadmium, bismuth, cobalt, copper, lead, manganese, nickel and zinc, only cadmium stimulated [3H]glucosamine incorporation, with a strong inhibition of the [35S]sulfate incorporation in the bovine cells. Characterization of bovine smooth muscle GAGs showed that the cadmium-induced increase in the [3H]glucosamine incorporation was mainly observed in heparan sulfate; the inhibition of the [35S]sulfate incorporation occurred non-selectively. Cadmium accumulated in bovine vascular smooth muscle cells in a dose-dependent manner with an increase in the leakage of lactate dehydrogenase into the medium. The present data suggest that vascular smooth muscle cells respond to the cytotoxicity of cadmium and promote the GAG synthesis with a reduction of their sulfation. It is postulated that this response may be a defensive one to the damage of the vascular tissue caused by cadmium but would be a component of the metal-induced atherosclerosis.

Animals↗
PubMed1994

Clinical significance of right ventricular dilatation in patients with right ventricular infarction.

BACKGROUND: Right ventricular infarction can be accurately diagnosed by ST-segment elevation in the right precordial leads. However, the clinical outcome of right ventricular infarction encompasses a wide spectrum, ranging from no hemodynamic compromise to cardiogenic shock. The present study examined the clinical significance of echocardiographic right ventricular dilatation in patients with right ventricular infarction. METHODS: We studied 60 consecutive patients with ECG evidence of right ventricular infarction (at least 1 mm ST-segment elevation and QS or QR in V4R) after their first acute Q-wave inferior infarction. They had been admitted to the coronary care unit within 24 h of the onset of chest pain. The presence of right ventricular dilatation was diagnosed when the end-diastolic ratio between right and left ventricle was more than 0.5 on two-dimensional echocardiogram. RESULTS: Of the 60 patients with ECG evidence of right ventricular infarction, 29 had right ventricular dilatation (group 1) and 31 did not (group 2). We used four clinical variables in multivariate analysis to determine the significant factors related to right ventricular infarction. Mean right atrial pressure and number of left ventricular segments with advanced asynergy were found to be the important factors. Furthermore, a significantly higher incidence of major complications (cardiogenic shock and need for temporary pacing) was observed in group 1 than in group 2. Right ventricular dilatation was found to be the significant factor related to major complications. CONCLUSION: Echocardiographic right ventricular dilatation is an important non-invasive sign obtained on admission in patients with right ventricular infarction, because it is associated with larger left ventricular infarct size and increased risk of major complications.

Aged↗
PubMed1994

Effect of FK-506 on xenografted human Graves' thyroid tissue is severe combined immunodeficient mice.

OBJECTIVE: We studied the macrolide antibiotic FK-506, an immunosuppressive agent, in an attempt to ameliorate the lesion of autoimmune thyroid disease in human thyroid tissue xenografted into severe combined immunodeficient (SCID) mice. It was not felt appropriate to employ this agent directly in patients with autoimmune thyroid disease because adequate therapeutic modalities are available and the introduction of new, experimental agents could not be justified. Moreover, the study of the tissue before and after treatment could not have been undertaken directly in patients. DESIGN: Human thyroid xenografts from four patients with Graves' disease and two normal persons were xenografted into SCID mice. Two weeks after xenografting, human immunoglobulin G (IgG) was detectable in all SCID mice xenografted with Graves' thyroid tissue. Mice were divided into two groups with human IgG levels similar to each other. Mice in the first group were treated with FK-506 daily for 6 weeks; mice in the second (similar) group were given phosphate-buffered saline (PBS) only (control group). MEASUREMENTS: Blood samples were taken every 2 weeks from the tail veins for human IgG, thyroid stimulating antibody, thyroperoxidase antibodies, thyroglobulin antibodies, and interferon-gamma (IFN-gamma). After 8 weeks treatment, animals were sacrificed; thyroid tissue was examined histologically and for thyrocyte HLA-DR expression. FK-506 was also added to thyrocytes in in-vitro tissue culture conditions. RESULTS: After 4-6 weeks of FK-506 therapy, human IgG, all thyroid antibodies and IFN-gamma were suppressed, while the levels remained elevated in the control group. Lymphocytic infiltration virtually disappeared in the human thyroid tissue of the FK-506-treated mice and thyrocyte HLA-DR expression markedly declined; in the control mice, lymphocytic infiltration remained heavy and HLA-DR expression remained high. On the other hand, FK-506 added directly to thyrocytes in vitro (without lymphocytes) did not reduce thyrocyte HLA-DR expression. CONCLUSIONS: FK-506 appears to suppress the activation of intrathyroidal lymphocytes, but not thyrocytes. From these observations, it is concluded that this agent, by its action on intrathyroidal lymphocytes, is able to ameliorate the immunologically mediated histological and serological disturbance in human autoimmune thyroid disease, at least under these circumstances.

Animals↗
PubMed1994

Weight carrying effects on treadmill exercise response in persons without heart disease.

To evaluate the effect of weight carrying on dynamic exercise response, 12 normal subjects were studied during treadmill exercise using ear densitography in two ways: (1) no weight, (2) 10 kg weight in one hand. Although there were no significant differences in diastolic time (DT), tension-time index [TTI: systolic blood pressure x heart rate (HR) x left ventricular ejection time (LVET)] was significantly higher throughout the weight carrying exercise compared to dynamic exercise. The amount of change (delta) in TTI was significantly larger in the initial stage (control to 1 min) of weight carrying exercise compared to dynamic exercise, but there were no significant differences in the later stages (1-3 min and 3-6 min). A prolongation in LVET was observed despite increasing HR during the first minute of exercise in both type of exercise, but LVET was longer at any given HR in weight carrying compared to dynamic exercise. Thus, despite higher TTI throughout the weight carrying exercise, delta TTI was larger only in the initial stage which was caused by prolongation of LVET resulting from disproportionate increase in venous return of early exercise.

Adult↗
PubMed1994

Effect of ventriculoarterial coupling on residual left ventricular pump function in diabetic patients with myocardial infarction.

To study the ventriculoarterial coupling in diabetic patients with myocardial infarction (MI), 26 diabetic and 34 nondiabetic patients were investigated using radionuclide angiography in the 3rd week after acute MI. Effective arterial elastance was nearly one half of left ventricular end-systolic elastance in nondiabetic patients. On the other hand, effective arterial elastance was twice left ventricular end-systolic elastance in diabetic patients. These data suggest that a decrease in left ventricular contractility and an increase in effective arterial elastance lead to increased potential energy and decreased work efficiency in diabetic patients.

Arteries↗
PubMed1994

cAMP responsive element-mediated regulation of the gene transcription of the alpha 1B adrenergic receptor by thyrotropin.

To elucidate the molecular mechanism of the stimulatory effect of thyrotropin on the gene regulation of alpha 1B adrenergic receptor in functioning rat thyroid (FRTL-5) cells, we established a competitive reverse-transcriptase (RT) polymerase chain reaction (PCR) and nuclear run-off assay to quantify changes in mRNA levels and transcription rates. A binding assay showed that FRTL-5 cells predominantly expressed alpha 1B adrenergic receptor and that thyrotropin increased its expression sevenfold. By means of RT-PCR, we found that thyrotropin induced an 11-fold increase in alpha 1B receptor mRNA abundance. The nuclear run-off assay demonstrated that thyrotropin caused a ninefold increase at the gene transcriptional level, which occurred in the presence of the protein synthesis inhibitor cycloheximide. The half-life of the alpha 1B receptor mRNA in cells incubated with thyrotropin for 1 h increased 1.5-fold but returned to the original value after 12 h. Dibutyryl cAMP and forskolin mimicked the stimulatory effects of thyrotropin on the gene transcriptional level. The 5'-flanking region of the rat alpha 1B receptor gene contained a putative cAMP responsive element (CRE) at nucleotide -438 relative to the translation start site. The promoter analysis using the reporter gene indicated that the CRE motif confers the cAMP sensitivity to the transcription of the rat alpha 1B receptor gene. These results demonstrated that a CRE-mediated mechanism is involved in the transcriptional regulation of the alpha 1B receptor gene by thyrotropin without requiring new protein synthesis.

Animals↗
PubMed1994

Cadmium stimulation of glycosaminoglycan synthesis by cultured vascular endothelial cells: comparison of various cell types.

We investigated the effect of cadmium on the synthesis of glycosaminoglycans (GAGs) in confluent cultures of vascular endothelial cells derived from bovine aorta. Cadmium markedly increased the incorporation of [3H]glucosamine into GAGs in both the cell layer and the conditioned medium but decreased [35S]sulfate in the cell layer. This suggested that cadmium induced the GAG synthesis by endothelial cells accompanied by a reduction of the sulfation of cell-associated GAGs. Of the tested heavy metals, the [35S]sulfate incorporation in the cell layer was significantly decreased by lead; zinc slightly but significantly increased the [35S]sulfate incorporation; manganese and copper failed to change the [3H]glucosamine and [35S]sulfate incorporation; and the incorporation of [3H]glucosamine was increased only by cadmium. On the other hand, vascular smooth-muscle cells and fibroblastic Balb/3T3 cells responded to cadmium in a way similar to vascular endothelial cells, while fibroblastic IMR-90 cells, Chang liver cells and epithelial LLC-PK1 cells altered the [3H]glucosamine and [35S]sulfate incorporation after exposure to cadmium in different manners. The alteration of GAGs induced by cadmium may be involved in the pathogenesis of the metal.

Animals↗
PubMed1994

Nucleosides and nucleotides. 131. Synthesis and properties of oligonucleotides containing 5-formyl-2'-deoxyuridine.

Thymidine was converted into 5-formyl-2'-deoxyuridine (1), which was incorporated into oligonucleotides, 5'd(GGAGA1CTCC)3' (I-1) and 5'd(GCTGC1GCGAAAGCTG)3' (II-1). To avoid side-reactions and degradation, protection of the formyl group of 1 using a newly developed protecting group, N,N-di-(3,5-dichlorophenyl)ethylenediamine, was necessary. Compound 1 was unstable under the conditions employed for enzymatic complete digestion of oligonucleotides, so that a peak corresponding to 1 was not detected clearly by HPLC analysis of a nucleoside mixture obtained by complete hydrolysis of I-1. Therefore, the oligonucleotide I-1 was treated with cyanomethylene-triphenylphosphorane to give an oligonucleotide containing (E) and (Z)-5-(2-cyanovinyl)-2'- deoxyuridine, which was then hydrolyzed, and the newly generated nucleosides were detected by HPLC analysis. The Tm of the self-complementary oligonucleotide I-1 (40 degrees C) was higher than that of the parent oligonucleotide, 5'd(GGAGATCTCC)3', (31 degrees C) in a buffer containing 0.01 M sodium phosphate (pH 7.0) and 0.1 M NaCl. DNA replication study on a template-primer system [primer, 5'd(32P-CAGCTTTCGC)3'; template, 3'd(GTCGAAAGCGXCGTCG)5' (X = 1 or T)] showed that dATP was incorporated into the DNA strand at a site opposite to 1 by Klenow DNA polymerase, but with a reduced rate. The formyl group of 1 in the oligonucleotides reacted with amines to give Schiff base derivatives.

Base Sequence↗
PubMed1993

Shaker-related potassium channel, Kv1.4, mRNA regulation in cultured rat heart myocytes and differential expression of Kv1.4 and Kv1.5 genes in myocardial development and hypertrophy.

The multiple K+ channels are crucial for repolarization and configuration of the action potential in the neuronal and cardiac cells. In this study, we report the regulatory mechanisms of rapidly inactivating Shaker Kv1.4 channel transcript in the rat heart. Quantitative PCR analysis showed that stimulation with high concentration of KCl, BAY-K 8644, or 12-O-tetradecanoyl phorbol-13-acetate resulted in an immediate and substantial increase (two- to threefold) of Kv1.4 mRNA levels in spontaneously beating myocytes prepared from neonatal rat ventricles. The Kv1.4 mRNA in the ventricle remains at a steady state level after birth and gradually declines with maturation. These results suggest that the Kv1.4 mRNA level is not static and undergoes dynamic modulation by multiple factors that activate intracellular signals. In addition, the expression patterns of Kv1.4 as well as the delayed rectifier Shaker K+ channel Kv1.5 mRNAs were examined in hypertrophied ventricles in which a plateau phase of action potential is remarkably prolonged. The Kv1.5 mRNA level was dramatically repressed while the Kv1.4 mRNA level was remarkably increased. This differential regulation was completely reversed by the normalization of hypertrophy, suggesting that the pathological alterations of K+ channel gene regulation may be involved in the occurrence of ventricular arrhythmias in hypertrophic hearts.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Measurement of erythrocyte Na,K-ATPase activity in normal pregnant women.

To investigate the peripheral metabolic status during normal pregnancy, we measured the number of erythrocyte Na,K-ATPase units as well as the cation transport activity of the pump from 32 normal pregnant women and 12 normal controls. The number of pump units determined by maximal ouabain binding to erythrocyte in normal pregnancy was significantly higher than that in normal controls (mean +/- SEM: 0.52 +/- 0.03 vs. 0.39 +/- 0.04 pmol/10(9)RBC, P < 0.05). The total cation transport activity of the pump measured by 86Rb uptake also significantly increased during pregnancy (98.9 +/- 6.4 vs. 73.1 +/- 5.4 nmol/10(9) RBC, P < 0.01). However, the mean cation transport activity per pump unit, which was presumed to be an indicator of the peripheral metabolic status, was unchanged in any of three trimesters when compared with that in normal controls. Serum FT4 levels measured by two different methods were significantly lower in the third trimester than in the first trimester (P < 0.01). In conclusion, erythrocyte Na, K-ATPase activity per pump unit is normal in pregnant women, suggesting that the peripheral metabolic status in pregnancy seems to be normal. Increases in both the number and function of the pump may be influenced by factors other than thyroid function.

Adult↗
PubMed1993

Changes in plasma atrial natriuretic peptide during hemodialysis: mechanism of elevated levels in patients with chronic renal failure.

An elevated plasma atrial natriuretic peptide (ANP) concentration was observed in patients with chronic renal failure, and it was significantly (P < 0.01) decreased by hemodialysis with or without fluid removal. The ANP concentration was decreased by dialysis without fluid removal and the decrease was significantly (P < 0.01) correlated with the pre-dialysis value. The decrease in this peptide during fluid removal without diffusion was significantly (P < 0.05) correlated with the decrease in the circulating plasma volume measured by dye dilution. The decrease in the ANP level was therefore considered to be related to a fall in right atrial pressure caused by the decline in the circulating plasma volume. The circulating plasma volume, osmotic pressure, and blood pressure were not changed by hemodialysis without fluid removal. Moreover, the filtrate concentration of ANP (mean: 5.5 pg/ml) during fluid removal without dialysis was only about 8% of the plasma level, so filtration of ANP from the dialyzer was negligible. The decrease in ANP during hemodialysis without fluid removal may therefore have been caused by the removal of or a change in the level of substances, for example electrolytes, epinephrine, and uremic toxins. In addition to volume expansion, such a substance(s) might influence plasma ANP levels in patients with chronic renal failure.

Adult↗