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Biomedical subjects

J Suzuki

Publications and source records attributed to J Suzuki.

At least 19 recordsLinked to original sources

Morphological onset and early diagnosis in apical hypertrophic cardiomyopathy: a long term analysis with nuclear magnetic resonance imaging.

OBJECTIVES: A long-term follow-up study with nuclear magnetic resonance (NMR) imaging was undertaken to detect the morphological onset and to establish the early diagnosis in apical hypertrophic cardiomyopathy (HCM). BACKGROUND: A spadelike configuration on left ventriculogram (LVG) is regarded as a diagnostic criterion for the classical apical HCM. There also exists a segmented hypertrophy at the apical level without indicating the spadelike features (a nonspade configuration). To detect the hypertrophied myocardium of the nonspade configuration, circumferential scrutiny of the apex is required. Although both configurations can be underlying causes of giant negative T waves, etiological relationship between the two is not clarified. METHODS: The criteria for the spadelike configuration defined on left ventricular short-axis NMR images were as follows: (apical maximal thickness > or = 15 mm), (apical anterior thickness over basal anterior thickness > or = 1.3) and (apical posterior thickness over basal posterior thickness > or =1.3). Thirteen patients who had predominant hypertrophy (> or = 15 mm) at the apical level without the spadelike configuration underwent NMR imaging twice before and after 54+/-10 months' follow-up. RESULTS: Apical hypertrophy that had been confined to the lateral wall in four, the anterior-lateral wall in two, and the septal-anterior wall in one developed to become circumferential hypertrophy that fulfilled the criteria for the spadelike configuration after the follow-up period. CONCLUSIONS: The spadelike configuration can begin with the nonspade configuration and therefore, both can constitute a single disease entity of apical HCM. The early diagnosis of apical HCM can be achieved by identifying the hypertrophy frequently confined to the lateral wall at the apical level.

Adult

Poor renal accumulation of 99mTc-DMSA in idiopathic tubular proteinuria.

In Japanese patients idiopathic tubular proteinuria presents mainly as asymptomatic tubular low molecular weight proteinuria. This disease has recently been shown to resemble Dent's disease which is characterized by tubular proteinuria, hypercalciuria, rickets and eventual renal failure. We report on 4 children with idiopathic tubular proteinuria. Although they had normal renal function, as evidenced by serum creatinine or creatinine clearance, they had very poor renal accumulation of 99mTc-DMSA and the presence of large amounts of tracer in the bladder. Additionally, the patient with the largest amounts of tubular proteinuria had the poorest renal accumulation of the 4 patients. The renal accumulation of tracer decreased with time from a maximum at 10 min after injection. These findings demonstrate that the tracer, once taken to be confined to the proximal tubular cells, is immediately excreted to the tubular lumen. We suggest that poor renal accumulation of 99mTc-DMSA is very important in elucidating the mechanism of idiopathic tubular proteinuria, and that 99mTc-DMSA renoscintigraphy is useful in the evaluation of the patient's renal function over time.

Adolescent

Early detection of anthracycline-induced cardiotoxicity by radionuclide angiocardiography.

For the early detection of myocardial damage associated with anthracycline therapy, electrocardiography, echocardiography, and radionuclide angiocardiography were used to assess cardiac function in 37 patients receiving anthracyclines (ie, adriamycin and daunorubicin at a total dose of 100-2,030 mg/m2). None of the patients developed clinical congestive heart failure. There were no significant changes of electrocardiographic and echocardiographic parameters after anthracycline administration. The left ventricular ejection fraction did not change significantly on radionuclide angiocardiography. However, the 1/3 peak filling rate (PFR) corrected by the end-diastolic count (EDC) (1/3 PFR/EDC) and the 1/3 filling fraction (1/3 FF), the indices of early diastolic function, showed a significant decrease. These findings suggest that the 1/3 PFR/EDC and 1/3 FF determined by radionuclide imaging are useful for detecting silent myocardial damage induced by anthracyclines.

Adult

Synergistic action of R-Ras and IGF-1 on Bcl-xL expression and caspase-3 inhibition in BaF3 cells: R-Ras and IGF-1 control distinct anti-apoptotic kinase pathways.

R-Ras and insulin-like growth factor-1 (IGF-1) synergistically inhibit apoptosis of BaF3 cells upon interleukin-3 deprivation. To characterize the mechanism of this synergistic inhibition, we examined the effect of R-Ras and IGF-1 on several apoptosis-related proteins. Extracellular signal-regulated kinase (ERK) was activated by IGF-1, but not by R-Ras. In contrast, Akt was activated strongly by R-Ras, but weakly by IGF-1. It was also found that R-Ras and IGF-1 cooperatively induced Bcl-xL expression and inhibited caspase-3 activation.

Apoptosis

Omega-3 polyunsaturated fatty acids--modulation of voltage-dependent L-type Ca2+ current in guinea-pig tracheal smooth muscle cells.

Omega-3 polyunsaturated fatty acids have been reported to be associated with favorable changes in the respiratory system. To determine one of the mechanisms for this effect, membrane currents were recorded in guinea-pig tracheal myocytes by using the whole-cell voltage clamp technique. Without EGTA in the patch pipette containing the Cs-internal solution, command voltage pulses positive to +0 mV from a holding potential of -60 mV elicited a voltage-dependent L-type Ca2+ current (I(Ca x L)) and a subsequent outward current. Upon repolarization, slowly decaying inward tail currents were recorded. The outward currents and the inward tail current were enhanced by methyl-1,4,-dihydro-2,6-dimethyl-3-nitro-4-(2-trigluromethylphenyl )-pyridine-5-carboxylate, and blocked by Cd2+ or nifedipine. Inclusion of EGTA (5 mM) in the patch pipette also abolished these currents, indicating that they were Ca2+-dependent. When [Cl-]o or [Cl-]i was changed, the reversal potential of these currents shifted, thus behaving like a Cl(-)-sensitive ion channel. 4,4'-Diisothiocyanatostilbene-2,2'-disulphonic acid. a Cl- channel blocker, inhibited the currents. The omega-3 polyunsaturated fatty acids eicosapentaenoic acid (3-30 microM) and docosahexaenoic acid (30 microM) suppressed I(Ca x L) and then inhibited I(Ca x Cl) in a reversible manner. Similar inhibitory effects of eicosapentaenoic acid on I(Ca x L) were observed with 5 mM EGTA in the patch pipette. Neurokinin A (1 microM) and caffeine (10 mM) also transiently activated I(Cl x Ca), probably due to Ca2+ release from Ca2+ storage sites. Pretreatment of the cells with eicosapentaenoic acid markedly suppressed the activation of I(Cl x Ca) by neurokinin A or caffeine. These results suggest that omega-3 polyunsaturated fatty acids inhibit voltage-dependent L-type Ca2+ currents and also Ca2+-activated Cl- currents in tracheal smooth muscle cells from the guinea-pig, which may play a role in modulation of tracheal smooth muscle tone.

Animals

Heart rate variability during the first month of smoking cessation.

BACKGROUND: Heart rate variability (HRV) is known to increase after smoking cessation. However, no work has been performed concerning HRV immediately after smoking cessation. METHODS AND RESULTS: We studied HRV before and from 1 day to 1 month after smoking cessation and also determined whether there is a relation between HRV and the withdrawal syndrome immediately after smoking cessation. We determined HRV by using a two-channel 24-hour ambulatory ECG system before and 1, 2, 3, 7, 14, 21, and 28 days after smoking cessation in 20 healthy male volunteers who had smoked one or more packs per day for 2 or more years. One day after smoking cessation, heart rate decreased significantly, and all 24-hour time and frequency domain indices of HRV increased except the standard deviations of the normal R-R intervals and the 5-minute mean R-R. The magnitude of increase in these indices peaked 2 to 7 days after smoking cessation and gradually decreased thereafter. The increase in HRV persisted 1 month after smoking cessation. In the 16 subjects with signs of withdrawal syndrome and in the four subjects without evidence of withdrawal before and immediately and 1 month after smoking cessation, HRV increased immediately after smoking cessation and remained elevated after 1 month. CONCLUSIONS: HRV increases immediately after smoking cessation and gradually declines thereafter, which suggests that the effect of smoking on autonomic activity rapidly disappears immediately after smoking cessation. HRV remained unaffected by the presence or absence of the withdrawal syndrome.

Adult

Sensitive diagnosis of cardiac allograft rejection by detection of cytokine transcription in situ.

OBJECTIVE: In situ transcription of cytokines which are important in the development of cardiac rejection has not been evaluated for diagnosing rejection. The objective was to evaluate the usefulness of in situ reverse transcriptase polymerase chain reaction (RT-PCR) for sensitive detection of acute cardiac rejection. METHODS: We studied interferon (IFN)-gamma and interleukin (IL)-2 expression using immunohistochemistry and in situ RT-PCR in murine cardiac transplant models. Hearts were heterotopically transplanted (BALB/c to C3H/He) and some mice were not treated (n = 23); others were treated with anti-intercellular adhesion molecule (ICAM)-1 and anti-lymphocyte function associated antigen (LFA)-1 monoclonal antibodies (mAbs) (n = 23). Allografts were removed at days 1 to 7. For control, isografts were harvested at day 7 (n = 2). RESULTS: Mice without treatment rejected allografts within 7 days, while all mAb-treated recipients accepted allografts for the same period. At day 1, allografts of both groups showed scattered myocardial cell infiltration which increased in non-treated allografts, but remained stable in mAb-treated grafts thereafter. In situ RT-PCR showed that IL-2 and IFN-gamma mRNA positive cells were present in non-treated allografts, while few mRNA positive cells were expressed in infiltrating cells in the mAb-treated allografts (IL-2, day 3: 88.8 +/- 28.3 vs. 7.2 +/- 6.4, p < 0.05, positive cells within 10 fields per section). However, immunohistochemistry could not reveal the difference at day 3. CONCLUSION: In situ RT-PCR is a sensitive method for diagnosing acute rejection, and it reveals the characteristics of myocardial infiltrate cells to determine their role in the process of rejection.

Animals

Prognosis following acute myocardial infarction in patients with ECG evidence of left ventricular hypertrophy prior to infarction.

This study was designed to determine the relationship between prognosis after myocardial infarction (MI) and left ventricular hypertrophy (LVH). Left ventricular hypertrophy diagnosed by electrocardiography according to the criteria of Sokolow and Lyon was noted in 57 of 223 patients (25.6%) on the pre-MI electrocardiogram (ECG), in 11.2% on an early post-MI ECG, and in 11.3% on the discharge ECG. In-hospital and 1-year postdischarge mortalities were significantly greater in patients with LVH noted on pre-MI ECG than in patients without prior LVH. There was no relationship between the presence of LVH on early post-MI ECGs and in-hospital or postdischarge 1-year mortality. Multivariate analysis revealed that evidence of LVH on a pre-MI ECG and acute congestive heart failure were independent predictors of cardiac death within 1 year of MI in patients over 70 years old. It is concluded that in patients over 70 years of age, the presence of LVH on a pre-MI ECG is a reliable predictor of post-MI prognosis.

Cause of Death

Antiepileptic effects of allopurinol on EL mice are associated with changes in SOD isoenzyme activities.

We have investigated the potential antiepileptic action of superoxide dismutase (SOD) activities in the brain of the epileptic mutant EL mouse. EL mice which experienced frequent seizures (EL[s]) had abnormally low levels of SOD isoenzyme activity in the hippocampal area. Once epileptogenicity was established in these animals, activity of cyanide-sensitive Cu,Zn-SOD was maintained at significantly lower levels than in control mice. However, cyanide-insensitive Mn-SOD activity was not different from non-epileptic controls. In EL mice which had not experienced seizure provoking stimulations and exhibited no seizures (EL[ns]) there was moderately lower levels of SOD isoenzyme activities compared to controls. In spite of the low level of Cu,Zn-SOD activity in EL[s] mice, the Cu,Zn-SOD protein content was high in the hippocampus of these animals, suggesting that inactive Cu,Zn-SOD might be induced during development. After allopurinol (ALP) was given orally to EL[s] mice, Cu,Zn-SOD activities increased dramatically in the hippocampus and seizure activity was decreased. Even after 48 h, when antiepileptic action of ALP was lost, the SOD activity was maintained at the high level associated with initial ALP administration. EL[s] mice also showed DNA fragmentation in the hippocampal CA1 region and the parietal cortex, detected with in situ terminal transferase-mediated dUTP nick labeling with the aid of alkaliphosphatase or peroxidase. The degree of DNA fragmentation was less severe in EL[ns] mice. We propose that abnormalities in region specific Cu,Zn-SOD isoenzyme activity might produce free radicals, leading to DNA fragmentations and cell loss. This might contribute to hippocampal epileptogenesis in EL mice.

Allopurinol

Analysis of apoptotic cell death in human hair follicles in vivo and in vitro.

We analyzed changes of growth and apoptotic cell death in human hair follicles. In anagen hair follicles, terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick labeling-positive cells were observed in the keratogenous zone of the upper bulb matrix, the inner root sheath, and the companion layer of the outer root sheath. DNA ladder formation was also detected in anagen hair follicles. In catagen hair follicles, the lower bulb matrix cells around the dermal papilla and the outer layer cells of the outer root sheath became strongly positive, showing that apoptosis in catagen hair is distinct from that in anagen hair. We also confirmed the mRNA expression of four caspases (caspase-1, caspase-3, caspase-4, and caspase-7) in anagen hair follicles by reverse transcriptase-polymerase chain reaction and in situ hybridization. When human anagen hair follicles were cultured in the presence of transforming growth factor-beta or tumor necrosis factor-alpha in the serum-free medium, transforming growth factor-beta but not tumor necrosis factor-alpha induced catagen-like morphologic changes, which were indistinguishable from normal catagen hair follicles. Tumor necrosis factor-alpha, however, strongly inhibited the elongation of the hair shaft in a dose-dependent manner, accompanied by abnormal morphology and increased cell death in the bulb matrix cells. Our results suggest that apoptosis in hair follicles involves two different types. One is related to the terminal differentiation of follicular epithelial cells in anagen hair. The other occurs as a major driving force to eliminate the distinct portion of epithelial components in catagen hair. Furthermore, this study strongly indicates that the transforming growth factor-beta pathway is involved in the induction of catagen phase in human hair cycle.

Antibodies

Functional characterization of renal chloride channel, CLCN5, mutations associated with Dent'sJapan disease.

BACKGROUND: The annual urinary screening of Japanese children above three years of age has identified a progressive renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrocalcinosis, and this represents a variant of Dent's disease. Hitherto, 12 mutations of the X-linked renal specific chloride channel, CLCN5, have been reported in the Dent'sJapan variant. To further identify such CLCN5 mutations and to define the structure-function relationships of this channel, we have investigated five unrelated, non-consanguinous Japanese families with this disorder. METHODS: Leukocyte DNA from probands was used with CLCN5 primers for PCR amplification of the coding region, and the DNA sequences of the products determined. Functional studies were performed by expressing the mutants in Xenopus oocytes. RESULTS: Five CLCN5 mutations consisting of two nonsense (R648X and R704X), two missense (S270R and L278F) and one acceptor splice site mutation (ag-->cg) in intron 4 were identified. The missense and splice site mutations represent novel abnormalities. Heterologous expression in Xenopus oocytes of wild-type and the missense mutants demonstrated that the mutations, which were translated, either abolished or markedly reduced chloride conductance. CONCLUSIONS: These results expand the spectrum of CLCN5 mutations associated with this renal disorder and provide insight into possible structure-function relationships. For example, both the missense mutations are located within a short putative loop between two transmembrane domains, and our results suggest that this region may have an important functional role in the regulation of channel activity.

Adolescent

Assessment of a new triple agent regimen for the eradication of Helicobacter pylori and the nature of H. pylori resistance to this therapy in Japan.

BACKGROUND: Multiple regimens for the eradication of Helicobacter pylori have been tested, but the best therapy has not been determined yet. To determine the efficacy of a new triple agent regimen using a combination of lansoprazole, amoxicillin, and clarithromycin against Helicobacter pylori (H. pylori), and to examine H. pylori resistance to this therapy in ineffective cases. METHODS: We studied a total of 71 patients infected with H. pylori who had gastric ulcer (n = 37) or duodenal ulcer (n = 34) as confirmed by endoscopy. Patients received 1500 mg amoxicillin, 400 mg clarithromycin and 30 mg lansoprazole for 2 weeks followed by 30 mg lansoprazole for 6 weeks in patients with gastric ulcer or for 4 weeks in those with duodenal ulcer. Endoscopic examination was performed before treatment and at 1 month, 2 months, and 5 months after initiating treatment to check the status of ulceration and H. pylori infection. RESULTS: The eradication rate of H. pylori was 92% (CI, 83-100%) in the gastric ulcer group and 94% (CI, 86-100%) in the duodenal ulcer group at 5 months, as determined by per-protocol analysis. Resistance to clarithromycin was present in 1 of 71 (1%) patients before treatment and in 2 of 5 (40%) patients after treatment. No resistance to amoxicillin and lansoprazole was found in patients before or after treatment. The resistance to clarithromycin changed during the observation period. CONCLUSIONS: The new triple agent regimen was effective against H. pylori. Resistance to clarithromycin may not be permanent and it might be one of the risk factors which affect the efficacy of a clarithromycin-based therapy.

Adult

Kinetics of intraocular cytokines in the suppression of experimental autoimmune uveoretinitis by type I IFN.

The systemic administration of IFN-alpha/beta was previously found to suppress inflammation in rats with experimental autoimmune uveoretinitis (EAU); however, an effect on the systemic immune response was not identified. In order to investigate an immunological basis for suppression at the intraocular level, rats immunized with interphotoreceptor retinoid-binding protein (IRBP) were administered daily intramuscular injections of 10(5) IU IFN-alpha/beta and cytokines were measured by ELISA in intraocular extracts prepared by ultrasonification at various timepoints throughout the course of EAU. In control EAU, intraocular concentrations of IFN-gamma were found to be non-detectable on day 8 before the onset of inflammation, significantly elevated on day 12 at peak inflammation (182+/-106 pg/ml), then non-detectable again on day 16 after inflammation had begun to subside. In contrast, intraocular IFN-gamma in IFN-alpha/beta-treated rats remained non-detectable or low at all timepoints. Measurement of intraocular IL-2 revealed no difference between the two groups of rats. Intraocular IL-4 concentrations were elevated in rats treated with IFN-alpha/beta, although this cytokine was also detected in the same range in controls as well as normal rats. Finally, intraocular IL-10 was non-detectable on day 8, significantly elevated at peak inflammation on day 12 (588+/-139 pg/ml), then decreased to low levels on day 16 in control EAU rats, while remaining non-detectable or low in IFN-alpha/beta-treated rats. These results suggest that acute inflammation in IRBP-induced EAU in rats involves both IFN-gamma and IL-10 at the local intraocular level, and that systemic administration of IFN-alpha/beta inhibits EAU via a mechanism that involves suppression of both cytokines.

Animals