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Biomedical subjects

A Shibata

Publications and source records attributed to A Shibata.

At least 109 records · Page 6Linked to original sources
PubMed1997

Expression of inducible nitric oxide synthase in rat experimental autoimmune myocarditis with special reference to changes in cardiac hemodynamics.

Excessive NO produced by an inducible NO synthase (iNOS) has been implicated in many types of immune-associated disorders of the cardiovascular system, but it remains to be determined whether NO plays a role in myocarditis. Thus, the significance of iNOS expression in the development of experimental autoimmune myocarditis (EAM), an animal model of human giant cell myocarditis, was investigated. Lewis rats were immunized with cardiac myosin and were killed 7, 14, 21, 28, and 49 days after immunization. The development of severe myocarditis was observed on days 14, 21, and 28 in association with significant deterioration of hemodynamics determined by cardiac catheterization, which peaked on day 21. In parallel with histological severity of myocarditis and deterioration of cardiac performance, iNOS activity in the heart measured by [14C]L-citrulline formation was markedly increased on days 14, 21, and 28. The expression of iNOS was confirmed by immunoblotting and was localized to the infiltrating inflammatory cells found in the vicinity of necrotic myocytes by immunohistochemical analysis. Aminoguanidine, a selective inhibitor of iNOS, significantly decreased the iNOS activity (1.04 +/- 0.37 compared with 29.1 +/- 8.62 pmol.min-1.mg protein-1 in untreated myosin-immunized rats, P < .01) and effectively attenuated histopathological changes of EAM on day 21. Hemodynamic parameters were also improved from 64 +/- 3 to 89 +/- 3 mm Hg for mean blood pressure, from 80 +/- 2 to 113 +/- 4 mm Hg for left ventricular systolic pressure, from 7.8 +/- 0.3 to 3.2 +/- 0.3 mm Hg for left ventricular end-diastolic pressure, from 2867 +/- 137 to 4180 +/- 102 mm Hg/s for +dP/dt, and from 2717 +/- 132 to 4180 +/- 184 mm Hg/s for -dP/dt (P < .01). The values after aminoguanidine treatment were not significantly different from the control values. These results suggest an important role for NO in mediating pathophysiological changes in myocarditis of autoimmune origin.

Animals↗
PubMed1997

Long-term evaluation of combined antihypertensive therapy with lisinopril and a thiazide diuretic in patients with essential hypertension.

For the treatment of hypertension, the combination of an angiotensin-converting enzyme (ACE) inhibitor and a thiazide diuretic is supported by multiple lines of evidence, because these drugs have synergistic action and are expected to cancel out each other's adverse side effects. However, the long-term outcome of this combination antihypertensive therapy is not entirely clear. In the present multicenter open trial, we investigated the long-term efficacy and safety of combined antihypertensive therapy with an ACE inhibitor, lisinopril, and a thiazide diuretic, trichlormethiazide. A total of 466 patients with essential hypertension were treated with lisinopril alone (monotherapy group, n = 360) or with a combination of lisinopril with trichlormethiazide (combination therapy group, n = 106) for 1 year. The average blood pressure was effectively lowered to below 150/90 mmHg in both the monotherapy and the combination therapy groups throughout the study period. The average maintenance dose of lisinopril was lower when combined with thiazide than when given alone (9.8 vs. 11.5 mg/day, p < 0.001). Dry cough was the major side effect of lisinopril; no severe adverse effects were observed. The incidence of cough was not significantly different between the monotherapy group (13.1%) and the combination therapy group (11.3%). The increase in serum potassium observed in the monotherapy group was reversed by the concurrent use of the thiazide diuretic in the combination therapy group. Fasting blood glucose was significantly reduced in the monotherapy group; the reduction observed in the combination therapy group was not significant. Thus, the present results provide useful information as to the effectiveness and safety of combined antihypertensive therapy with lisinopril and a thiazide in comparison with monotherapy with lisinopril.

Adult↗
PubMed1997

[Comparison of long-term survival between bone marrow transplantation and maintenance chemotherapy for adult acute lymphoblastic leukemia in first remission].

To clarify the efficacy of allogeneic bone marrow transplantation (BMT) for adult ALL in first remission we retrospectively studied long-term outcomes of adult ALL patients of age between 15 and 44 years who were treated in our institute from 1980 to 1990. In this period thirteen patients with HLA compatible donors were offered allogeneic BMT during the first remission, while 16 patients without HLA-compatible donor were treated with maintenance chemotherapy (Cancer Chemoth Pharmacology 33:359-365, 1994). Patient and disease characteristics (age, leukocyte count at presentation, immunophenotype, Ph1 chromosome, and duration to first remission) in the two groups were not significantly different (chi-square test p > 0.1). As causes of treatment failure, relapse was 90% for chemotherapy while relapse and therapy-related death were 67% and 33%, respectively, for transplantation. The leukemia-free survival (LFS) rates at 10 years were 52 +/- 13% for transplantation and 30 +/- 11% for chemotherapy (P > 0.2, g-Wilcoxon, Logrank). The 10-year-LFS rates of Ph1-negative patients of 15 to 29 year-old were 67 +/- 15% for transplantation (n = 9) and 62 +/- 15% for chemotherapy (n = 8) (P > 0.9). Although the present data are derived from a non randomized retrospective study and a relatively small number of patients, this study revealed no superiority of BMT over chemotherapy for the prolongation of first remission in adult ALL, especially, in a standard risk group such as young patients without Ph1 chromosome.

Adolescent↗
PubMed1997

Presence of p53 mutations in primary nasopharyngeal carcinoma (NPC) in non-Asians of Los Angeles, California, a low-risk population for NPC.

Mutatins of the p53 tumor suppressor gene are rare in nasopharyngeal carcinoma (NPC) patients who reside in high-risk areas, such as Southeastern China. Among this high-risk group, a pre-existing infection with the EBV and consumption of Cantonese salted fish are closely associated with NPC. We investigated the prevalence of p53 mutations in 28 primary NPC specimens from white (including Hispanic) and African-American patients in Los Angeles, who are at low risk for NPC. Using PCR-based single-strand conformational polymorphism and direct sequencing, we found four mutations (14%) in exons 5-8 of the p53 gene in four patients. All were C-to-T transition mutations: two were present in exon 5-one at codon 142 [CCT (Pro)-->CTT (Leu)] and another at codon 144 [CAG (Gln)-->TAG (stop codon)]. The other two mutations were identified in exon 8: one at codon 273 [CGT (Arg)-->CAT (His)], a CpG site, and one at codon 271, a silent mutation [GAG (Glu)-->GAA (Glu)]. This is the first report investigating the presence of p53 missense mutations in NPC among a low-risk population. Our data indicate that p53 is also an infrequent event among NPC patients at low risk for the disease.

Adolescent↗
PubMed1996

Myelin-associated glycoprotein inhibits neurite/axon growth and causes growth cone collapse.

We have previously shown that myelin-associated glycoprotein (MAG) inhibits neurite growth from a neuronal cell line. In this study we show that 60% of axonal growth cones of postnatal day 1 hippocampal neurons collapsed when they encountered polystyrene beads coated with recombinant MAG (rMAG). Such collapse was not observed with denatured rMAG. Neurite growth from rat embryonic hippocampal and neonatal cerebellar neurons was also inhibited about 80% on tissue culture substrates coated with rMAG. To investigate further the inhibitory activity of MAG in myelin, we purified myelin from MAG-deficient mice and separated octylglucoside extracts of myelin by diethylaminoethyl (DEAE) ion-exchange chromatography. Although there was no significant difference in neurite growth on myelin purified from MAG-/- and MAG+/+ mice, differences were observed in the fractionated material. The major inhibitory peak that is associated with MAG in normal mice was significantly reduced in MAG-deficient mice. These results suggest that although MAG contributes significantly to axon growth inhibition associated with myelin, its lack in MAG-deficient mice is masked by other non-MAG inhibitors. Axon regeneration in these mice was also examined after thoracic lesions of the corticospinal tracts. A very small number of anterogradely labeled axons extended up to 13.2 mm past the lesion in MAG-/- mice. Although there is some enhancement of axon generation, the poor growth after spinal cord injury in MAG-/- mice may be due to the presence of other non-MAG inhibitors. The in vitro studies, however, provide the first evidence that MAG modulates growth cone behavior and inhibits neurite growth by causing growth cone collapse.

Animals↗
PubMed1996

Identification of cis-acting elements involved in an alternative splicing of the amyloid precursor protein (APP) gene.

Our previous study demonstrated that a cis-acting element for neuron-specific splicing of human amyloid precursor protein (APP) gene existed in an intron region flanking to exon 8 (Yamada et al., 1993). In this study, we extended the analysis by deletion and mutagenesis experiments and identified two distinct cis-acting elements which modulate the splicing of exon 8 of the APP gene in a sequence-dependent manner. Both elements are located at the just upstream region of the so-called branchpoint sequence, the first (ATGTTT) at -42 to -47 nt and the second (TTT) at -36 to -38 nt upstream from exon 8. Our study suggested that the first one is a positive element for the splicing of exon 8 and the second a negative one for the splicing.

Alternative Splicing↗
PubMed1996

Transcriptional regulation of squalene epoxidase by sterols and inhibitors in HeLa cells.

Regulation of squalene epoxidase (SE) gene expression was studied in comparison with those of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and low density lipoprotein (LDL) receptor. An increased expression of SE mRNA and protein content in mouse L929 cells grown in 10% lipoprotein-deficient fetal bovine serum (LPDS) for 48 h was found by performing immunoblot and Northern blot analyses when compared with the culture in the presence of fetal bovine serum (FBS). The same results in mRNA levels were seen using human cell lines HepG2, HeLa, and Chang liver cells. The increase of SE mRNA in HeLa cells grown in LPDS was preventable in a dose-dependent manner by feeding cells with 25-hydroxycholesterol or cholesterol. When an SE inhibitor, NB-598, was fed to HeLa cells grown in LPDS, it caused further increases in mRNA levels of SE, HMG-CoA reductase, and LDL receptor. In contrast, NB-598 had no effect on the message levels of these genes when fed to HeLa cells grown in FBS. These results suggest that sterol produced endogenously can also regulate SE expression at the level of transcription.

Animals↗
PubMed1996

Clinical evaluation of serum amlodipine level in patients with angina pectoris.

Serum amlodipine levels were determined in 18 patients with vasospastic angina. Patients were divided into two groups: Group A (n = 9) received amlodipine 5 mg by single daily administration, and Group B (n = 9) received 10 mg given by single daily administration for the first 3 days, then 5 mg from the 4th day on. The serum amlodipine concentration in Group A took 7 days to reach a steady state of around 8 ng/ml. The level in Group B was 8.9 ng/ml at 3 days. From these results, the optimal dosage of amlodipine in the treatment of angina pectoris is 10 mg for the initial 3 days followed by 5 mg thereafter.

Aged↗
PubMed1996

Vascular thromboxane formation in hemostasis mechanism: correlation between bleeding time and vascular TXB2 in a patient with congenital platelet cyclo-oxygenase deficiency.

We encountered a patient with congenital platelet cyclo-oxygenase deficiency with normal ability to synthesize vascular prostaglandin I2 (PGI2) and thromboxane A2 (TXA2). The patient's peripheral blood monocytes did not show cyclo-oxygenase (COX) activity, but cultured bone marrow fibroblasts showed COX activity. To determine the mechanism of primary hemostasis in this patient, we examined the effect of oral administration of aspirin (1 g) on bleeding time and thromboxane B2 (TXB2), 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha) production in the blood emerging from the incision in this patient. The bleeding time was markedly prolonged by the administration of aspirin, and this prolongation was associated with the inhibition of TXB2 in the effluent blood, which seemed to be derived from the vessel wall. These findings suggest that vascular TXA2 production plays an important role in the maintenance of hemostasis.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Case Report: amyopathic dermatomyositis associated with transformed malignant lymphoma.

Amyopathic dermatomyositis is a disease of unknown origin characterized by the specific skin lesions of dermatomyositis but without clinical or laboratory evidence of myopathy. During the past 15 years, a great controversy between the different reports concerning a possible association of dermatomyositis with malignancy has been noted. In this report, the authors describe a patient with amyopathic dermatomyositis who presented first with a benign hyperplasia of the lymph node, which finally transformed into frank malignant lymphoma. In addition to follow-up care, screening tests to search for occult malignancy in patients with amyopathic dermatomyositis (or dermatomyositis) are recommended.

Aged↗
PubMed1996

Two cases of ventricular parasystole associated with ventricular tachycardia.

In two patients, ventricular parasystole (VP) was associated with ventricular tachycardia (VT), and in one patient, catheter ablation was successful. In patient 1, with dilated cardiomyopathy, VP led to VT, which converted to ventricular fibrillation. In patient 2, VP led to symptomatic nonsustained polymorphic VT. The origin of parasystolic focus was determined by endocardial mapping, and a radiofrequency current was delivered to patient 2. Both VP and VT disappeared immediately, and no recurrence has been observed during a follow-up of 8 months. Catheter ablation to the parasystolic focus was effective and a relationship between VP and VT was strongly suggested.

Cardiomyopathy, Dilated↗
PubMed1996

Electrophysiological findings in idiopathic recurrent ventricular fibrillation: special reference to mode of induction, drug testing, and long-term outcomes.

Electrophysiological studies can be useful in the presence of idiopathic ventricular fibrillation (VF) and may be used when selecting antiarrhythmic drugs. However, the yield, the mode, and the long-term reproducibility of the induction of VF have not yet been fully elucidated. Eight patients with idiopathic VF underwent electrophysiological study. The mean age (+/- SD) was 45 +/- 17 years. Six were males and two were females. Diagnosis was done by exclusion. VF was induced in 6 (75%) of 8 patients using double extra stimuli at coupling intervals of 233 +/- 39 and 191 +/- 20 ms for the first and second extra stimuli, respectively. Of note, VF was induced by stimulation exclusively at the origin of the premature ventricular beat, which was the first complex of VF in two patients. In another patient, VF was initiated by two premature stimuli and also by a pause produced by rapid pacing. The inducibility of VF was reproduced 9-18 months after the first induction in all of the four patients studied. When the ability of antiarrhythmic drugs to suppress VF inducibility was confirmed, no recurrence was observed during the follow-up period of 40-160 months, but a recurrence of VF was observed in one of two nonresponders. In one patient, amiodarone administration failed in preventing VF induction 9 months after initiation of therapy, and reassessment of long-term drug-efficacy might be indicated in some patients. In conclusion, idiopathic VF was highly inducible (75%) with double extra stimuli. In this study, it was induced from a specific site (2/8) or by a pause (1/8). Induction of VF seemed to be reproduced 9-18 months after the first study. The outcome was considered favorable when the inducibility of VF was suppressed by antiarrhythmic drugs.

Adolescent↗
PubMed1996

Drug-induced narrowing of the width of the zone of entrainment as a predictor of the subsequent non-inducibility of reentrant ventricular tachycardia after an additional dose of an antiarrhythmic drug.

BACKGROUND: The efficacy of drugs used to treat inducible monomorphic sustained ventricular tachycardia (VT) has been assessed by investigating their ability to suppress inducibility, but the mechanism of the drug action remains to be determined. OBJECTIVES: To determine electrophysiological variables that predict inducibility, divided doses of class I antiarrhythmic drugs were given and their effects were analysed, particularly the ability of the final dose to suppress inducibility. METHODS: The excitable gap was estimated by the zone of entrainment, which was defined as the difference between the cycle length of VT and the longest paced cycle length that interrupted VT during entrainment of VT with rapid pacing at paced cycle lengths in decrements of 10 ms. The cycle length of VT, the block cycle length, and the zone of entrainment were measured in the drug free state and after intermediate and final doses of procainamide, disopyramide, cibenzoline, and mexiletine. RESULTS: Sustained monomorphic VT with a mean (SD) cycle length of 285 (43) ms was induced in 8 patients. It was entrained and interrupted at the block cycle length of 231 (31) ms. The width of the zone of entrainment was 54 (23) ms. In 8 studies VT was not inducible at final doses of procainamide in 4, cibenzoline in 1, and mexiletine in 3. In another 10 studies (procainamide in 4, disopyramide in 1, cibenzoline in 2, and mexiletine in 3), VT remained inducible at the intermediate dose and at the final dose. The cycle length of VT was prolonged to a similar degree in studies of effective and ineffective drugs, but the cycle length that blocked VT was longer at the intermediate dose of the effective drugs. Consequently, the width of the zone of entrainment was significantly narrowed at the intermediate dose of effective drugs and the width of the zone of entrainment was narrower than when ineffective drugs were given (22 (13) ms v 76 (18) or 75 (37) ms at the intermediate and final doses respectively (P < 0.02). CONCLUSION: Drugs that narrowed the zone of entrainment were associated with non-inducibility of VT after the final dose of the drug was given. The baseline variables did not predict the responses to class I antiarrhythmic drugs.

Adult↗
PubMed1996

Discrepant effects of mexiletine on cycle length of ventricular tachycardia and on the effective refractory period in the area of slow conduction.

OBJECTIVE: Monomorphic sustained ventricular tachycardia (VT) can often be entrained and interrupted at a critical paced cycle length. The aim was to evaluate a possible determinant of this phenomenon by observing the action of mexiletine on the critical paced cycle length and other variables. METHODS: Nine consecutive patients with symptomatic VT were studied. After induction of VT, the area of slow conduction was mapped as the earliest site of the activation or the site with mid-diastolic potential during the tachycardia. Rapid pacing was performed at a site distant from the tachycardia circuit to entrain the tachycardia, starting at a cycle length 10-20 ms shorter than the VT cycle length, and repeated after a decrement of the cycle length in steps of 10 ms to obtain the longest paced cycle length that interrupted the tachycardia: the block cycle length. The effective refractory period (ERP) was measured at the pacing site at which the myocardium was presumed to be normal and also in the area of slow conduction. The effects of mexiletine on the cycle length of VT, the block cycle length, and the ERP at two sites were obtained before and after mexiletine administration. The relation between the cycle length of VT and block cycle length and their changes were also analysed. RESULTS: 11 VTs with the same morphology were induced before and after mexiletine administration. The VT cycle length was prolonged by mexiletine from 309 (SD 53) to 361 (47) ms, and it was interrupted at block cycle lengths of 247 (37) and 307 (41) ms, respectively, the changes being 18 (12)% and 23 (8)% (both P < 0.001). All VTs were entrained, and during pacing at the block cycle length there was abrupt loss of fusion and change in the presystolic electrogram, always associated with interruption of VT on cessation of rapid pacing. A good correlation was observed between the VT cycle length and the block cycle length (r = 0.77 to 0.80). The ERP at the pacing site (normal myocardium) and in the area of slow conduction showed no significant change: 241 (21) v 240 (22) ms and 262 (9) v 252 (9) ms, respectively. The block cycle length was longer than the ERP after mexiletine administration: 362 (55) v 252 (9) ms (P < 0.02). CONCLUSIONS: Mexiletine prolonged the cycle length of VT and the VT-interrupting critical cycle length but not the ERP. The prolongation of the VT cycle length and the block cycle length by mexiletine seemed to be unrelated to the action potential duration, but related to depressed intercellular conduction.

Action Potentials↗
PubMed1996

Clockwise whirlpool sign at color Doppler US: an objective and definite sign of midgut volvulus.

PURPOSE: To evaluate the clockwise whirlpool sign at color Doppler ultrasound (US) in the diagnosis of midgut volvulus. MATERIALS AND METHODS: Pediatric patients (160 boys, 76 girls; age range, 0 day to 14 years) with possible midgut volvulus underwent abdominal gray-scale US and color Doppler US. Midgut volvulus was diagnosed by recognition of the whirlpool sign (wrapping of the superior mesenteric vein and the mesentery around the superior mesenteric artery). If the whirlpool rotated clockwise with caudal movement of the transducer, the direction of the whirlpool was defined as clockwise. RESULTS: Color Doppler US showed a whirlpool sign that was clockwise in 12 of 13 patients with surgically confirmed midgut volvulus and counterclockwise in three patients without midgut volvulus. Sensitivity, specificity, and positive predictive value of clockwise whirlpool sign for midgut volvulus were 92%, 100%, and 100%. CONCLUSION: The clockwise whirlpool sign is diagnostic of midgut volvulus. Color Doppler US should be performed as an initial imaging study in children suspected of having midgut volvulus.

Adolescent↗