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Biomedical subjects

M Korenaga

Publications and source records attributed to M Korenaga.

At least 19 recordsLinked to original sources
PubMed1999

Differences in hypervariable region 1 quasispecies of hepatitis C virus in human serum, peripheral blood mononuclear cells, and liver.

Hepatitis C virus (HCV) has been reported to potentially replicate in peripheral blood mononuclear cells (PBMCs), but direct information on the pathogenic implication of HCV infection in PBMCs is still limited. To investigate this issue, we compared the complexity of HCV quasispecies in serum, PBMCs, and livers of 13 patients with type C chronic liver disease. Hypervariable region 1 (HVR 1) was amplified by reverse-transcription polymerase chain reaction (RT-PCR), and the PCR products were subcloned and sequenced. Considerable differences in the complexity of HVR 1 quasispecies were found in the serum, PBMCs, and liver in all patients, and the predominant sequences from each source were mutually different in 3 (23%) patients. An amino acid sequence unique to each source existed as well as a sequence common to serum and PBMCs, common to serum and livers, or common to PBMCs and liver. These results suggest infection of PBMCs by HCV, and that HCV in PBMCs may be differently exposed to host immunity from that in liver.

Adult↗
PubMed1999

Factors predicting progression to cirrhosis and hepatocellular carcinoma in patients with transfusion-associated hepatitis C virus infection.

The clinical progression of chronic hepatitis C is not uniform throughout the entire period of infection and is more rapid in patients with advanced histologic disease. Our study was designed to identify factors contributing to progression to cirrhosis and hepatocellular carcinoma by taking the entire period of infection into consideration. Two hundred thirteen patients with transfusion-associated hepatitis type C chronic liver disease were included in this study. They did not have either a history of antiviral therapy or any other potential causes of chronic liver disease except for transfusion. Hepatitis C virus genotype 1b was detected in 144 (68%) patients, followed by 2a in 51 (24%), 2b in 11 (5%), 1a in 4 (2%), and coinfection with 1b and 2a in 3 (1%). The log-rank test in the Kaplan-Meier method revealed that the cumulative percentage of cirrhosis-free or hepatocellular carcinoma-free patients became significantly lower as the transfusion age went up. Patient age at the time of transfusion was the only independent factor related to disease progression in multivariate analysis using Cox's proportional hazards model. Thus age at transfusion should be taken into consideration in designing the optimal follow-up schedule and therapy in patients with posttransfusion-associated chronic hepatitis C.

Adult↗
PubMed1998

Exogenous interleukin-3 enhances IL-4 production by splenic CD4+ cells during the early stages of a Trichinella spiralis infection.

Treatment with recombinant interleukin-3 (rIL-3) augmented IL-4 production of spleen cells in mice infected with Trichinella spiralis. In a previous report, we showed that treatment with rIL-3 accelerated IgE responsiveness in mice. We have examined IL-4 and interferon (IFN)-gamma production by spleen cells from both rIL-3-treated and untreated mice during the early stages of infection. The results indicated that IL-4 production was enhanced in rIL-3-treated mice compared to that in untreated mice. In contrast, there was no difference in IFN-gamma production between the two groups. Augmentation of IL-4 production was dependent on the dose of rIL-3 injected before infection. To examine if the treatment with rIL-3 affects T cell function, spleen cells from mice treated with various doses of rIL-3 were cultured under the stimulation with anti-CD3 (T cell receptor complex) mAb and then assessed for cytokine production. IL-4 production increased depending on the dose of rIL-3, while IFN-gamma production did not. Furthermore, spleen cells were separated by surface markers, Thy1.2, CD4 and CD8. Thy1. 2+ cell population responded significantly to produce IL-4 after anti-CD3 stimulation, when compared with IL-4 production of Thy1.2- cell population. A major producer of IL-4 in T cells was CD4+ cell population but not CD8+ cell population. IL-4 production was suppressed in rIL-3-treated mice injected with anti-CD4 mAb. These results suggest that IL-3 might play a role as Th2 amplifier in immune response to parasite infection.

Animals↗
PubMed1997

Differences in hypervariable region 1 quasispecies between immune complexed and non-immune complexed hepatitis C virus particles.

Antibody to the hypervariable region 1 of hepatitis C virus (HCV) is thought to have neutralizing activity. The complexity of hypervariable region 1 quasispecies was compared between immune complexed and non-immune complexed HCV particles. Immune complexes and non-immune complexes, including intact HCV virions, were separated by differential flotation centrifugation and immunoprecipitation, and immune complexes were observed in 9 of 11 patients with chronic hepatitis C. Considerable differences in both hypervariable region 1 quasispecies and predominant clones were demonstrated between immune complexes and non-immune complexes in 4 patients and not in 5 patients. These results suggest that the specificity of antibody to hypervariable region 1 is related to the formation of immune complexes and that escape mutants with highly different quasispecies are resistant to neutralization by antibody to hypervariable region 1.

Adult↗
PubMed1997

Correlation between relative number of circulating low-density hepatitis C virus particles and disease activity in patients with chronic hepatitis C.

Hepatitis C virus (HCV) circulates as particles having differing buoyant densities. Changes in the relative proportions of virus particles of different densities were examined in 19 patients with chronic hepatitis C: 6 without (group A) and 13 with (group B) abnormal serum alanine aminotransferase (ALT) levels. High- and low-density virus particles were separated by differential flotation centrifugation. The numbers of high-density particles consistently exceeded that of low-density particles in all patients in group A, whereas the titers of both types of particles were the same at least once in 7 of 10 patients sampled at two time points in group B. The ALT level significantly increased <2 months later (P < 0.05) when the titers of both types of particles were the same in patients in group B. Thus, we found a correlation between the relative numbers of circulating low-density HCV particles and disease activity in chronic hepatitis C patients.

Adult↗
PubMed1997

Longitudinal dissociation in the his bundle: a possible mechanism of two distinct cycle lengths in atrioventricular reentrant tachycardia.

Two wide QRS tachycardias with identical morphology but different cycle lengths (CLs) developed in a 63-year-old man. Electrophysiological study demonstrated inducible atrioventricular reentrant tachycardia (AVRT) due to a concealed left posterior accessory pathway (AP), which was successfully ablated by radiofrequency application. Neither dual AV nodal pathways nor other APs were documented. Splitting of the His-bundle electrogram was shown, and programmed stimulation induced sudden prolongation of intra-hisian conduction time. These results suggest longitudinal dissociation in the His bundle may be responsible for two distinct CLs in AVRT without dual AV nodal physiology.

Bundle of His↗
PubMed1996

Injection of recombinant interleukin 3 hastens worm expulsion in mice infected with Trichinella spiralis.

The effects of interleukin 3 (IL-3) on worm expulsion were studied in mice infected with Trichinella spiralis. C3H/He mice were treated with a total of 10(4) U IL-3 or saline by daily peritoneal injection from day-5 to day-1. Muscle larvae were given orally to both groups of mice on day 0. The muscle worn burden in infected mice was assessed on day 28. The worm burden in mice treated with recombinant IL-3 (rIL-3) was significantly suppressed as compared with that in control mice. A reduction in the worm burden was observed in mice treated with rIL-3 from day-5 to day-1 but not in those treated day 16 to day 20. This suggests that IL-3 could up-regulate the host defense response to intestinal worms but not to parenteral stage worms. When various doses of rIL-3 were given to mice and the intestinal worm burden was assessed on day 5, protection was observed only in mice treated with a total of 10(4) U rIL-3 but not in those given either 3.5 x 10(3) or 10(3) U. A kinetics study on the recovery of intestinal adult worms showed that rIL-3 treatment hastened worm expulsion. The mucosal mast-cell response observed in the small intestine of rIL-3-treated mice was induced earlier and was greater than that seen in the control. The host defense response induced by rIL-3 could not be inhibited by treatment with anti-IL-4 or anti-IL-5 monoclonal antibody. Under such an experimental condition in this study, at least, the numbers of mast cells per villus crypt unit observed in mice treated with rIL-3 and anti-IL-4 antibody were slightly lower than those seen in mice treated with rIL-3, but the difference was not significantly different. These results suggest that IL-3 can induce the expulsion of T. spiralis worms without the cooperation of IL-4 or IL-5 in mice.

Animals↗
PubMed1996

Acceleration of IgE responses by treatment with recombinant interleukin-3 prior to infection with Trichinella spiralis in mice.

Treatment of mice with recombinant interleukin-3 (rIL-3) accelerated an IL-4-dependent IgE production following infection with Trichinella spiralis. When mice were treated with a total of 1.5 x 10(4) units rIL-3 for 5 days before infection with 400 muscle larvae, the serum IgE level increased prominently on day 5. Acceleration of IgE responses was dependent on the dose of rIL-3 injected. Treatment of mice with a total of 10(3) units rIL-3 could accelerate IgE responses. IgE responses were detected by a sandwich enzyme-linked immunosorbent assay at least from day 3 in mice treated with rIL-3. Acceleration of IgE responses was inhibited by anti-IL-4 monoclonal antibody. In contrast to this, IgG1 and IgG2a responses were not suppressed by the anti-IL-4 treatment. IL-3 treatment could up-regulate IgE and IgG1 responses but not the IgG2a response. IL-3 treatment could also accelerate IgE responses in W/Wv mice infected with the parasites. These results suggest that IL-3 is involved in regulation of IgE responses in mice and that mast cells do not play an essential role in acceleration of IgE responses induced by rIL-3 treatment in this system.

Animals↗
PubMed1996

Second case of zoonotic Onchocerca infection in a resident of Oita in Japan.

A non-gravid female Onchocerca was found in histopathological sections of a biopsy specimen taken from a painful nodule in the wrist of a 57-year old woman in Oita, in southern Japan. Six species of Onchocerca have been found in animals in Japan: two in wild bovids, one in equids, and three in domestic bovids of which one, Onchocerca sp., is only known by the microfilaria and infective stage. Distinctive morphological features of the worm, including a three-layered thick cuticle with prominent annular ridges at wide intervals, high somatic muscles and narrow lateral chords, resembled those of O. gutturosa, one of the three bovine Onchocerca species transmitted in the Oita region. However Onchocerca sp., which is also transmitted in this region, cannot be excluded. An ELISA test of the patient serum suggests that infections by Onchocerca spp. might be distinguished from those by Dirofilaria immitis, of which the number of human cases is increasing in Japan.

Animals↗
PubMed1996

Does appropriate endurance exercise training improve cardiac function in patients with prior myocardial infarction?

OBJECTIVE: The objective of the present study was to determine whether appropriate endurance exercise training improves cardiac function in patients with prior myocardial infarction. METHODS: Twenty-nine patients with prior myocardial infarction were divided into three groups (Group 1: control, Group 2: low-intensity training, Group 3: high-intensity training). Low and high training intensities were determined according to the gas exchange threshold of each patient. The patients in Groups 2 and 3 performed 15 min of home-based physical training safely, twice a day, 5 days a week for 2 months. Prior to and following this training, each patient performed two constant work rate tests (moderate and heavy intensity) and a symptom-limited incremental exercise test. RESULTS: Heart rates at rest and during exercise were decreased significantly after 2 months in all three groups. Stroke volume at rest increased significantly after 2 months only in Group 3. Stroke volume after 6 min of heavy-intensity exercise increased significantly in Groups 2 and 3. However, the ejection fraction at 6 min of heavy-intensity exercise increased significantly only in Group 3. The maximal work rate attained during incremental exercise testing increased significantly in Groups 2 and 3. This parameter did not significantly change in the control group. CONCLUSIONS: Effects of physical training on maximal exercise capacity were noted in both exercise training groups. However, improvement in cardiac function (such as stroke volume), both at rest and during exercise, was noted only in the high-intensity training group. Our results suggest that relatively high-intensity training may improve exercise capacity and cardiac function of patients with prior myocardial infarction.

Adult↗
PubMed1996

[Effects of nicorandil on coronary collateral circulation depend on the donor arteries].

The effects of nicorandil on coronary collateral circulation during exercise-induced ischemia were compared between the different donor arteries in 13 patients with effort angina, 7 with complete obstruction of the left anterior descending artery (LAD) with well-developed collateral vessels from the right coronary artery (RCA) (LAD group), and 6 with complete occlusion of the RCA (segment 2-3) with well-developed collateral vessels from the LAD (RCA group). Initial percentage thallium (%TI) uptake (thallium-201 single photon emission computed tomography) and washout rate were measured in the anterior, septal and posterior regions during ergometer exercise. The submaximal treadmill exercise test was also performed using a cardiopulmonary monitoring system to measure Vo2 at anaerobic threshold (AT). After the controls were obtained, nicorandil (15 mg/day) was administered for 4 weeks, during which ergometer exercise and treadmill exercise tests were carried out repeatedly. A significant improvement of initial %TI uptake on exercise was observed in the LAD group with nicorandil therapy, but no improvement was shown in the RCA group. The AT significantly increased after nicorandil treatment in the LAD group (13.9 +/- 0.38-->16.8 +/- 1.18 ml/min/kg), reflecting the improvement of cardiac function through the increased collateral flow. However, in the RCA group, it remained unchanged, suggesting no improvement of cardiac function. Nicorandil was effective to increase collateral flow from the RCA, but ineffective on that from the LAD. Nicorandil is an effective coronary dilator and is reported to affect both large and small coronary arteries. The effect on the collateral circulation is dependent on the donor artery supplying different areas. The vasodilator effect of nicorandil is mainly on the LAD, which is large enough to supply blood to a wider area of the heart, rather than the RCA.

Adult↗
PubMed1995

Effects of nicorandil on kinetics of oxygen uptake at the onset of exercise in patients with coronary artery disease.

The beneficial effects of coronary vasodilators on exercise capacity in patients with angina pectoris are well known. However, their effects on oxygen uptake (VO2) kinetics at the onset of exercise have not been elucidated. The present study was undertaken to determine the acute effects of nicorandil, a newer coronary vasodilator, on the kinetics of VO2 at the onset of exercise in patients with ischemic heart disease. Ten patients with significant coronary stenosis performed constant mild-intensity cycle exercise (32 +/- 3 W) for 6 minutes after oral administration of 10 mg of nicorandil or an identical placebo in a double-blind, crossover manner. Nicorandil had no effect on resting heart rate, blood pressure, or VO2. However, the time constant for the increase in VO2 during constant work rate exercise was significantly shorter (the kinetics of VO2 were faster) after administration of nicorandil than after placebo (46.5 +/- 13.3 vs 51.1 +/- 11.9 seconds; p = 0.039). The increase in VO2 at 6 minutes compared with 3 minutes of constant work, which reflects the VO2 kinetics, also was reduced with nicorandil (3.8 +/- 37.9 vs 27.5 +/- 27.1 ml/min; p = 0.022). Nicorandil was found to increase the rate of VO2, increase during the onset of constant work rate exercise, probably as a result of an improved response in cardiac output. Analysis of VO2 kinetics provides new and useful parameters for the evaluation of circulatory adjustments at the onset of exercise in patients with ischemic heart disease.

Adult↗
PubMed1995

Cross-resistance between Strongyloides venezuelensis and S. ratti in mice.

Cross-resistance between Strongyloides venezuelensis and S. ratti was tested in mice. The mice were immunized with S. ratti and challenged with infective filariform larvae or larvae recovered from the lungs of mice, of a heterologous species, S. venezuelensis. In this system, cross-resistance was expressed to the intestinal stage but not to the migrating stage of the parasite. Anti-interleukin (IL)-5 monoclonal antibody (mAb) treatment showed that peripheral blood eosinophilia after infection with both species of the genus Strongyloides was dependent on IL-5. Cross-resistance expressed to the intestinal stages was inhibited partially by injection of anti-IL-5 mAb.

Animals↗
PubMed1994

Regulatory effect of anti-interleukin-5 monoclonal antibody on intestinal worm burden in a primary infection with strongyloides venezuelensis in mice.

The intestinal worm burden in Strongyloides venezuelensis-infected mice was influenced by treatment with anti-interleukin-5 (IL-5) monoclonal antibody (NC17) when NC17 was given to mice 3-7 days before infection. The present study has examined the involvement of IL-5 in susceptibility at different in the development of the parasite in the host. The results show that the number of tissue-migrating larvae recovered from the lungs in a primary infection was not affected by anti-IL-5 monoclonal antibody treatment, whereas intestinal worm counts increased in mice treated with 0.25-1 mg of NC17. In mice treated with 0.1 mg of NC17, adult worm recovery was not significantly different from non-treated controls. Peripheral and tissue eosinophilia were not observed in the early phase of infection (days 4-8). Six days after transfer of lung-stage larvae to NC17-treated mice, adult worm recovery was higher than that of control mice. These results suggest that non-eosinophil response(s), which were dependent on IL-5, were involved in the initial establishment of the intestinal stage of S. venezuelensis in mice. We discuss the mechanisms that control the susceptibility to the parasite from the viewpoint of host defence.

Animals↗
PubMed1994

Oxygen uptake kinetics are determined by cardiac function at onset of exercise rather than peak exercise in patients with prior myocardial infarction.

BACKGROUND: Resting cardiac function does not necessarily affect exercise capacity. However, to determine whether it affects early dynamics of oxygen uptake (VO2) during exercise, we measured VO2 during a constant work rate and during incremental exercise testing in patients with a history of myocardial infarction. VO2 kinetics and exercise capacity were compared between patients with relatively high left ventricular ejection fractions (LVEF > or = 35%, group 1) and those with lower ejection fractions (LVEF < 35%, group 2). METHODS AND RESULTS: Forty patients with a history of prior myocardial infarction (age, 57 +/- 10 years) were monitored during 6 minutes of moderate constant work rate testing (40 +/- 8 W) and during symptom-limited incremental exercise testing with a cycle ergometer. VO2 was calculated from respired gas analysis on a breath-by-breath basis. Cardiac output determinations were made with a computerized cadmium telluride detector every 10 seconds during exercise. The VO2 time constant during constant work rate exercise was slower in group 2 (58.0 +/- 7.6 seconds) compared with group 1 (45.8 +/- 10.5 seconds, P = .0002), indicating slower kinetics in group 2. The time constant for the rise in cardiac output during exercise was also slower in patients with lower EFs (63.0 +/- 12.8 versus 50.0 +/- 12.2 seconds). However, there were no differences in exercise capacity parameters, such as the VO2 or cardiac output at peak exercise, obtained during incremental exercise testing among the two groups. CONCLUSIONS: The prolonged time constant of VO2, which is primarily determined during early parts of exercise, reflects delayed cardiac output response in patients with severely impaired LV function. The time constant of VO2 during submaximal constant work rate exercise can be used as a sensitive and discriminant measure of impaired cardiac reserve in these patients.

Adult↗
PubMed1991

In vivo administration of antibody to murine IL-5 receptor inhibits eosinophilia of IL-5 transgenic mice.

We investigated the in vivo role of interleukin 5 (IL-5) and its receptor (IL-5R) in eosinophil growth and differentiation. When mice were administered IL-5 i.p., an increase in the number of eosinophils was observed within 5 days in peripheral blood and the peritoneal cavity. Hypereosinophilia was observed in IL-5 transgenic mice who displayed constitutive production of IL-5. A binding assay with 35S-labeled IL-5 revealed the presence of two classes of IL-5 binding sites (low and high affinity) on the surface of eosinophils. IL-5Rs on eosinophils were recognized using mAbs against murine IL-5R. When the IL-5 transgenic mice were passively administered with anti-murine IL-5R mAbs, the number of recognizable eosinophils in peripheral blood dropped within 5 days to normal levels. The antibody treatment also prevented the increase in the number of eosinophils in IL-5-injected mice. The inhibition of the above experimental eosinophilia was also observed by the passive administration of anti-IL-5 mAb. The results of the in vivo experiments clearly demonstrate that IL-5 plays an essential role in in vivo eosinophilopoiesis and may be acting on eosinophils or their precursors directly through IL-5Rs, resulting in preferential growth of this lineage of hematopoietic cells. It can also be stressed that IL-5 regulates a specific lineage of hematopoietic cells (eosinophils).

Animals↗
PubMed1991

The role of interleukin-5 in protective immunity to Strongyloides venezuelensis infection in mice.

We depleted or neutralized interleukin-5 (IL-5) and IL-5 receptor of C57BL/6 mice, using rat anti-murine IL-5 monoclonal antibody (NC17) and anti-murine IL-5 receptor monoclonal antibody (H7). Mice treated with these monoclonal antibodies were infected with Strongyloides venezuelensis larvae. The time-course of faecal egg output and peripheral eosinophilia were monitored. In a primary infection, anti-IL-5 treatment did not affect faecal egg output, although the eosinophil count in peripheral blood was markedly reduced. There was no difference in intestinal worm burden or faecal egg output between anti-IL-5 treated and non-treated mice. In a secondary infection, worms were expelled from the small intestine of anti-IL-5-treated mice as well as from non-treated mice. Worm recovery from the lungs of mice treated with either anti-IL-5 or anti-IL-5 receptor monoclonal antibody was the same as that of normal controls. However, a marked reduction in worm recovery was observed in re-infected mice that had not been treated with monoclonal antibodies. Treatment with anti-IL-5 or anti-IL-5 receptor monoclonal antibody suppressed blood and tissue eosinophilia. Thus the results suggested that the host's protective immunity against tissue-migrating larvae was IL-5-dependent but intestinal immunity was not.

Animals↗