Biomedical subjects

T Onodera

Publications and source records attributed to T Onodera.

At least 55 records · Page 3Linked to original sources

PubMed1999

Role of interleukin-2 in pancreatic islet-cell destruction in reovirus type 2-infected DBA/1 suckling mice.

Reovirus type 2 (Reo-2)-infected DBA/1 suckling mice develop insulitis, resulting in a diabetes-like syndrome. In this study, the role of interleukin-2 (IL-2) in the death (destruction) of pancreatic islet cells was examined. The endogenous IL-2 activity of splenic cells in infected mice was greater than that in uninfected mice. Treatment of infected mice with monoclonal antibody against IL-2 prevented the development of insulitis with impaired glucose tolerance, in a dose-dependent manner. These results suggest that IL-2 may participate in pancreatic islet-cell destruction in Reo-2-induced diabetes-like syndrome.

Animals↗

PubMed1999

Effect of hand paddles on anaerobic energy release during supramaximal swimming.

PURPOSE: Swimmers swim faster using hand paddles. In this study the effect of maximal performance using hand paddles on aerobic and anaerobic energy release during supramaximal swimming was examined by comparing the maximal accumulated O2 deficit, and the aerobic and anaerobic energy release during exhaustive swimming with paddles (P) to swimming without paddles (hands only, H). METHODS: The subjects were six trained college male swimmers. Experiments were carried out in a swimming flume. The water flow rate was set before each exercise bout such that exhaustion occurred in 30 s, 1 min, or 2-3 min. Accumulated O2 deficit during exercise was determined by the accumulated oxygen demand minus the accumulated O2 uptake. RESULTS: Water flow rates at which maximal accumulated O2 deficit was obtained were significantly higher in P than that in H. However, mean values of maximal accumulated O2 deficit during H and P were 2.40+/-0.42 L and 2.32+/-0.37 L, respectively, and there was no significant difference between these two values. Furthermore, during the supramaximal swimming to exhaustion in 30 s, 1 min, or 2-3 min, both accumulated O2 uptake and accumulated O2 deficit did not significantly differ between these conditions, although mean water flow rates of these supramaximal swimming bouts were significantly higher in P than those in H again. CONCLUSIONS: These results suggest that the faster swimming speed accomplished with hand paddles does not affect metabolic responses and that it may be realized by recruitment of roughly the same muscle mass. Therefore, the ability to swim faster with hand paddles might mainly be attributed to other than metabolic factors, i.e., a higher propelling efficiency.

Adult↗

PubMed1999

Leishmania amazonensis infection in nude mice.

Leishmania amazonensis is an intracellular protozoan parasite of macrophages. Cutaneous leishmaniasis in an immunocompetent host begins as papules or nodules followed by ulceration at the site of promastigote inoculation. In this study, the pathological changes of cutaneous leishmaniasis lesions in T cell deficient nude mice were examined. When infected with L. amazonensis promastigotes, nude mice developed non-ulcerative cutaneous nodules. By histological examination of cutaneous lesions, massive accumulation of vacuolated histiocytes containing amastigotes was observed in all the nude mice. Although infiltration of mononuclear and polymorphonuclear cells was seen in the lesions of immunocompetent mice, few such cells were observed in the lesions of nude mice. These results indicate the importance of T cells on the ulcer formation in cutaneous leishmaniasis.

Animals↗

PubMed1999

Hyaluronic acid suppresses the reduction of alpha2(VI) collagen gene expression caused by interleukin-1beta in cultured rabbit articular chondrocytes.

In order to investigate how alpha2(VI) collagen gene is regulated by inflammatory cytokines in cultured rabbit articular chondrocytes, we examined the effect of interleukin-1beta (IL-1beta) on this collagen mRNA expression. Polylayer cultures of chondrocytes were exposed to IL-1beta (0.1, 1, 10 ng/ml). Quantitative detection of specific mRNA for this collagen was carried out by reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, to investigate the effect of hyaluronic acid (HA) on alpha2(VI) collagen mRNA expression by IL-1beta chondrocytes were exposed to IL-1beta (10 ng/ml) in the presence of HA (0.01, 0.1, 1 mg/ml) with molecular weight of 900 kDa. Chondrocytes were also exposed to IL-1beta (10 ng/ml) in the presence of HA (1 mg/ml) with molecular weights of 200, 900 and 2000 kDa. Alpha2(VI) collagen mRNA expression was decreased significantly in chondrocytes cultured with 1 and 10 ng/ml of IL-1beta. However, the addition of both IL-1beta and HA (0.1, 1 mg/ml) or both IL-1beta and HA (1 mg/ml) with all the molecular weight significantly suppressed these reduced mRNA levels. No tendency for this suppression to depend on the molecular weight was observed. These results suggest that suppression of transcriptional activity for type VI collagen will be associated with the reduction of cartilage matrix tissue and that HA will be associated with the suppression of the effect of IL-1beta.

Adjuvants, Immunologic↗

PubMed1999

Exacerbated spongiform lesions in the cerebral cortex in Japanese sheep, in an outbreak of scrapie during 1984-1987.

The present study dealt with the pathology of natural scrapie in Japanese Suffolk sheep in a certain selected area. Vacuolations in the cytoplasm of neurons were conspicuous. They were particularly evident in many areas of the medulla and pons, extending into and through pedunculus cerebri and thalamus to the septal area and olfactory tubercle. Proliferation of astrocytes was also easily observed with glial fibrillary acidic protein staining. Neural vacuolations in the cerebral cortex were observed in 73% of the cases. Abnormal prion protein deposits were seen in all cases observed by hydrolytic autoclaving, and subsequent peroxidase and anti-peroxidase immunostaining. Abnormal prion protein staining was the most conspicuous in the polymorphic layers of the hippocampus.

Animals↗

PubMed1998

Promoter analysis of the human mismatch repair gene hMSH2.

The human DNA mismatch repair gene homologue hMSH2 is involved in hereditary nonpolyposis colorectal cancer. We isolated and characterized the 5' upstream region, about 4.4kbp, of the hMSH2 gene. This region contains CpG islands and a number of elements involved in constitutive expression, but there is no TATA-box nearby the transcription start points. This is the typical structure for many promoters of housekeeping genes. Alu sequences and mononucleotide repeats are clustered in this region and there are two transcription start points. Deletion analysis revealed that less than 300bp was sufficient to initiate transcription. Although no mutation that influences promoter activity of this region was found, a polymorphism was detected by PCR-RFLP analysis. Because informative cases (C/T heterozygous) were relatively high ( approximately 30%), this polymorphism is suitable for a marker to examine allelic losses.

Alleles↗

PubMed1998

Regional myocyte hypertrophy parallels regional myocardial dysfunction during post-infarct remodeling.

After large myocardial infarction (MI), left-ventricular (LV) remodeling is characterized by cavity dilatation, eccentric hypertrophy, and regional mechanical dysfunction. We wished to correlate cellular hypertrophy chronically after MI with in vivo function on a regional basis within non-infarcted myocardium. Twelve sheep were studied. Seven underwent coronary ligation to create an anteroapical MI. Magnetic resonance imaging (MRI) was performed once in controls, and prior to and 8 weeks after infarction, for measurement of LV mass, volumes, ejection fraction, and regional intramyocardial circumferential shortening (%S). Myocyte morphometric indices (cell volume, length, cross-sectional area, width, and length/width ratios) were measured from myocytes isolated from regions adjacent to (within 2 cm of the infarct border) and remote from the infarct and at corresponding loci in the control animals. From baseline to 8 weeks after infarction in the infarcted animals, end-diastolic volume increased from (mean+/-s.d.) 1.9+/-0.4 ml/kg to 2.6+/-0.4 ml/kg (P<0.02) and EF fell from 49+/-6 to 35+/-6% (P<0.02). LV mass trended upwards from 2.2+/-0.4 to 2.6+/-0.4 g/kg (P=n.s.). Regionally, %S in the region adjacent to the infarct fell (from 19+/-3 to 13+/-3%, P<0.003) while remote %S did not change. Cell volume in adjacent non-infarcted regions was greater than that in remote non-infarcted regions (3.8+/-0.9x10(4) micrometer3 v 2.6+/-0. 8x10(4) micrometer3, P<0.006) and this difference (+1.2+/-0.7x10(4) micrometer3) was greater than the corresponding regional difference in controls (+0.4+/-0.2x10(4) micrometer3, P<0.05). Similarly, myocytes in adjacent non-infarcted regions were longer (138.0+/-10.1 micrometer) than in remote regions (123.7+/-10.1 micrometer, P<0.002), and this difference (+14.3+/-7.2 micrometer) was greater than that in controls (-1.4+/-5.6 micrometer, P<0.003). Adjacent %S correlated inversely with adjacent myocyte cell volume (r=-0.72, P<0.009) and cell length (r=-0.70, P<0.02). In mechanically dysfunctional non-infarcted regions adjacent to chronic transmural myocardial infarction in the remodeled LV, disproportionate cellular hypertrophy occurs, predominantly due to an increase in cell length. Mechanical dysfunction in these regions correlates with cell lengthening and hypertrophy.

Animals↗

PubMed1998

Correlation of myocyte lengthening to chamber dilation in the spontaneously hypertensive heart failure (SHHF) rat.

Chronic congestive heart failure of various etiologies is characterized by progressive chamber dilation. Although myocyte lengthening is involved, it is not known if this cellular change can account for all of the chamber dilation. The controversy is due largely to technical limitations in collecting data on chamber circumference, myocyte length, and sarcomere length simultaneously. To address this issue, the contributions of myocyte and sarcomere lengthening to progressive chamber dilation in spontaneously hypertensive heart failure (SHHF) rats was examined using a new approach. Female SHHF rats (n=31) were examined at various time points between 2 months of age and the onset of end-stage heart failure (18 months or older). A new method enabled simultaneous collection of data on myocyte length, sarcomere length, and chamber circumference using formalin-fixed tissue. Reliability of cellular measurements was confirmed with an alternate method. LV myocyte length increased linearly between 2 and 24 months of age due to series addition of sarcomeres. Myocyte length increased in direct proportion to chamber circumference during this period (r=0.93, P<0.001). Results suggest that myocyte lengthening alone can account for chamber dilation in the progression to heart failure. Excessive myocyte lengthening is a slow, progressive change that begins long before clinical signs and symptoms of heart failure appear in this model of hypertension and failure. Since myocyte remodeling in hypertensive humans with and without failure is known to resemble that in SHHF rats, these data should provide important insight into chamber dilation and the progression of heart failure in humans.

Animals↗

PubMed1998

New method to evaluate myocyte remodeling from formalin-fixed biopsy and autopsy material.

BACKGROUND: Excessive lengthening of cardiac myocytes attributed to series addition of sarcomeres is a consistent feature of left ventricular dilation in chronic heart failure. Currently, it is not feasible to assess myocyte dimensions, particularly myocyte length, in a manner that is of potential diagnostic usefulness. METHODS AND RESULTS: Isolated myocytes from three groups of normal rats (100, 200, and 300 g) were obtained by using two different methods: (1) digestion of formalin-fixed myocardial tissue using potassium hydroxide (KOH) and (2) retrograde aortic perfusion of fresh hearts with collagenase. There was no difference in mean cell length between the two methods. The KOH method was also used to isolate intact, rod-shaped myocytes from formalin-fixed human cadaver left ventricles (control, n = 3; heart failure, n = 3) and from human right ventricle biopsy specimens (n = 6). Confirming our previous work using collagenase-isolated myocytes from fresh human explants, left ventricular myocytes from failing hearts showed longer mean cell length compared with control hearts. Data from human right ventricle biopsy specimens confirmed our previous finding in rats that myocyte lengthening is less pronounced in this chamber in heart failure. CONCLUSIONS: The KOH method can be used to obtain reliable measurements of myocyte length and other cellular parameters from myocardial biopsies and autopsy material. Such data may be useful in the diagnostic assessment of remodeling associated with heart failure.

Aged↗

PubMed1998

Interferon-gamma plays a role in pancreatic islet-cell destruction of reovirus type 2-induced diabetes-like syndrome in DBA/1 suckling mice.

Reovirus type 2 (Reo-2) infection in DBA/1 suckling mice causes insulitis, which leads to pancreatic islet-cell destruction, resulting in a diabetes-like syndrome. T-helper (Th) 1 cytokines are thought to play a key role in islet inflammation in insulin-dependent diabetes mellitus. We examined this hypothesis in the Reo-2-induced diabetes-like syndrome. We used reverse transcriptase polymerase chain reaction (PCR) and quantitative PCR techniques to examine mRNA expression of interferon (IFN)-gamma (Th1 type cytokine), and interleukin (IL)-4 (Th2 type cytokine) in splenic cells. We observed that in Reo-2 infected mice the level of IFN-gamma expression increases with the development of insulitis, whereas expression of message for IL-4 is minimal to detectable with the immuno-inflammatory process 10 days after infection. The treatment of monoclonal antibody (mAb) against mouse IFN-gamma during the expansion phase of insulitis (5-9 days after infection) inhibited the development of insulitis and the elevation of blood glucose concentrations in a dose dependent manner. Furthermore altered CD4+/CD8+ cell ratio compared with uninfected mice in the splenic cells by the infection was recovered to the ratio of uninfected mice by the treatment of mAb against mouse IFN-gamma, suggesting normalization of T cell balance in immune system. These results suggest that Reo-2-triggered autoimmune insulitis may be mediated by Th1 lymphocytes and IFN-gamma may play a role in islet inflammation leading to islet cell destruction.

Animals↗

PubMed1998

Electrophysiologic and hemodynamic effects of a single oral dose of pilsicainide hydrochloride, a new class 1c antiarrhythmic agent.

To establish the clinical efficacy of pilsicainide, we evaluated its electrophysiologic and hemodynamic effects after a single oral administration to 18 patients with documented supraventricular tachycardia (SVT). To determine the minimal effective blood level, changes in efficacy with time were evaluated by serial reinduction studies with venous blood sampling for measurement of the plasma pilsicainide level. Sixty minutes after administration of a single oral dose of pilsicainide, the sinoatrial conduction time, AH and HV intervals, and the effective refractory period of the right ventricle were prolonged. Ventriculoatrial conduction was blocked in 11 patients [nine of 12 via accessory pathway and two of six via the atrioventricular (AV) node], resulting in the suppression of SVT induction in nine of 13 patients. Pilsicainide increased the heart rate and mean pulmonary arterial pressure and decreased the stroke volume index at 60 min. PQ interval, QRS width, and QTc were significantly prolonged after pilsicainide, and the percentage prolongations of the PQ interval were well correlated with the plasma pilsicainide levels. The plasma level effective for suppression of SVT was considered to be >0.5 microg/ml. We concluded that a single oral administration of pilsicainide is well tolerated and effective in suppressing SVT.

Administration, Oral↗

PubMed1998

Activation of 11 beta-hydroxysteroid dehydrogenase by dehydroepiandrosterone sulphate as an anti-hypertensive agent in spontaneously hypertensive rats.

The anti-hypertensive properties of dehydroepiandrosterone sulphate (DHEAS) have been investigated by studying its effects on blood pressure, on serum concentrations of corticosterone and dehydrocorticosterone, and on 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity in spontaneously hypertensive rats (SHR). SHR were given intraperitoneal injections of DHEAS (10 mg day-1 for 70 days) from six to 16 weeks of age. The blood pressure-time curve was significantly (P < 0.05) suppressed immediately after administration of DHEAS. There was no difference between the heart rates of control and DHEAS groups. Serum concentrations of corticosterone and dehydrocorticosterone in the DHEAS group were significantly (P < 0.05) lower than those of the control group. The dehydrocorticosterone/corticosterone concentration ratio was, however, significantly (P < 0.05) higher in the DHEAS group, suggesting that treatment with DHEAS enhanced the overall interconversion of corticosterone to dehydrocorticosterone. The activity of 11 beta-HSD in specific organs of the DHEAS group was affected, characteristic changes being increases in the kidney (14-58%), decreases in the liver (11-27%) and no change in the testis. Direct addition of DHEAS to 11 beta-HSD preparations from the kidneys of control SHR had the same effect as that observed in the in-vivo experiments. The fall in serum corticosterone in the DHEAS group is considered to be related, at least partly, to increased activity of kidney 11 beta-HSD. The inverse correlation of kidney 11 beta-HSD activity with serum corticosterone and blood pressure (-r = 0.628, P < 0.01, and -r = 0.478, P < 0.05, respectively) suggest that DHEAS delayed the development of hypertension in SHR by selective promotion of kidney 11 beta-HSD activity which in turn resulted in lower serum concentrations of corticosterone and its minimal aldosterone-like activity.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1998

Maladaptive remodeling of cardiac myocyte shape begins long before failure in hypertension.

Progression to failure in hypertension is associated with ventricular dilation, excessive myocyte lengthening, and an increase in myocyte length/width ratio. The temporal development of these changes in relation to impaired pump performance is unknown. We examined isolated myocytes from 1- to 12-month-old spontaneously hypertensive heart failure (SHHF) rats who develop heart failure at approximately 24 months of age. Left ventricular myocyte cross-sectional area reached a maximum of approximately 350 to 400 microm2 at 3 months of age and did not change significantly thereafter. Nonetheless, LV systolic wall stress, a known stimulus for myocyte transverse growth, increased progressively between 3 and 12 months of age. Unlike the situation in normally aging rats with stable body mass, myocyte length in SHHF rats continued to increase with aging (P<0.05 from 9 to 12 months of age). In summary, (1) left ventricular myocyte transverse growth reaches an upper limit by 3 months of age although systolic wall stress continues to rise; and (2) cell length is significantly increased by 12 months of age. This study suggests that maladaptive remodeling of cardiac myocyte shape begins long before pump failure in hypertension. Additionally, it appears that the left ventricle may be robbed of an important adaptive mechanism to normalize wall stress (eg, myocyte transverse growth) early in the progression to failure.

Aging↗

PubMed1998

Evaluation of equine infectious anemia virus core proteins produced in a baculovirus expression system in agar gel immunodiffusion test and enzyme-linked immunosorbent assay.

Equine infectious anemia virus (EIAV) core proteins (Gag and p26) obtained from a baculovirus expression system were used in agar gel immunodiffusion (AGID) and enzyme-linked immunosorbent assay (ELISA) antigens to test seventy-six horse sera. Those sera showed false-positive reaction in AGID test using Nisseiken antigen. However, none of them showed false-positive reaction with both of the expressed antigens. The 76 horse sera were also tested by ELISA. The sera gave a high background in ELISA using Nisseiken antigen. Gag and p26 reacted strongly against positive sera from horses immunized with Nisseiken antigen.

Animals↗

PubMed1998

Lipid peroxidation, antioxidative enzyme activities, and cytosolic free calcium levels in rat hippocampus-derived cells exposed to free radicals.

To elucidate mechanisms of free radical-induced neuronal cell death, lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS), three antioxidative enzyme activities (superoxide dismutase, glutathione peroxidase, and catalse), and cytosolic free Ca2+ (Ca2+i) were examined in rat hippocampus-derived cells (HV16-4) exposed to free radicals generated by a hypoxanthine-xanthine oxidase system. The viability of cells decreased with an increase in numbers of free radical positive cells in a dose-dependent manner of xanthine oxidase. The protein-bound TBARS did not change, whereas free TBARS increased at 135% of initial value. No remarkable change was observed in three antioxidative enzyme activities. On the other hand, Ca2+i increased after exposure followed by cell death. Furthermore, the addition of Co2+, a nonspecific Ca2+ channel blocker, delayed the increase of Ca2+i and subsequent cell death. These findings suggested that the influx of Ca2+ played a crucial role for HV16-4 cell death induced by free radicals.

Animals↗

PubMed1998

Cloning and characterization of a new swine MHC (SLA) class II DQB allele.

Major histocompatibility complex (MHC) of pigs is known as swine leukocyte antigen (SLA). The cDNA encoding a new allele of SLA class II DQ beta-chain was successfully isolated from a CSK miniature pig (derived from Göttingen strain) and characterized by sequence analyses. SLA-DQB cDNA fragment encoding beta 2-domain was amplified by reverse transcriptase-polymerase chain reaction using the sequences preserved in a various vertebrates as primers. Using non-radioisotope technique with the PCR product as a probe, cDNA clone G01 was isolated from a spleen cDNA library, and nucleotide sequence of this clone was determined. This clone encompassed a whole SLA-DQ beta-chain coding region, containing a total length of 1161 nucleotides with an open reading frame (ORF) of 786 nucleotides, 5' untranslated region of 15 nucleotides, and 3' untranslated region of 360 nucleotides ending with a canonical polyadenylation signal, followed by a poly A tail. Sequence comparisons of the ORF of this clone with those of known SLA-DQB genes confirmed that this clone is a new allele (SLA-DQB*G01). Phylogenetic analysis of the nucleotide sequences of swine, human, and murine MHC class II genes indicated that SLA-DQB was more similar to HLA-DQB1 than H-2A beta. Comparison of the nucleotide and deduced amino acid sequences among SLA-DQB alleles showed that the SLA-DQ beta-chain polymorphism was found almost in beta 1-domain which contains the antigenic peptide binding sites.

Alleles↗

PubMed1997

Endometrial carcinoma in 45,X Turner's syndrome without hormone replacement therapy.

An endometrial carcinoma developing in a patient with pure Turner's syndrome was described. The patient showed typical Turner's phenotype and analysis of karyotype revealed only 45,X. Secondary sexual development had been seen until age 20 and she had no history of hormone replacement therapy (HRT). The enlarged uterus and normal appearance of bilateral ovaries were detected at laparotomy. A well-differentiated adenocarcinoma of the endometrium and a graafian follicle of the left ovary were histologically confirmed. This seems to be the first report of the occurrence of endometrial carcinoma in possibly pure Turner's syndrome without HRT.

Adult↗

PubMed1997

Dimethylthiourea reduces pancreatic islet-cell damage in DBA/1 sucking mice with reovirus type-2 infection.

Reovirus type 2 (Reo-2) infection in DBA/1 sucking mice causes pancreatic islet-cell destruction, which results in a diabetes-like syndrome. To investigate the role of reactive oxygen species (ROS), the protective effect of dimethylthiourea (DMTU) was examined, this substance being an effective scavenger of hydroxyl radicals. The degree of cellular infiltration in and around pancreatic islets was the same in mice receiving either virus only or virus and DMTU. The latter had no effect on (1) the number or type of white blood cells, (2) lymphocyte function-associated antigen 1-alpha-positive splenocytes, or (3) viral multiplication in the pancreas. However, treatment with DMTU inhibited the elevation of blood glucose concentrations and reduced pancreatic islet-cell damage (beta-cell degranulation and necrosis). These results suggest that ROS play a role in the pathogenesis of Reo-2-induced diabetes-like syndrome.

Animals↗