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Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 235 records · Page 13Linked to original sources

Lack of association between T-786-->C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene and essential hypertension.

Accumulating evidence strongly suggests that an alteration in nitric oxide metabolism is involved in the pathogenesis of hypertension. We recently found 2 polymorphisms in the endothelial nitric oxide synthase (eNOS) gene, a Glu298Asp missense variant in exon 7 and a T-786-->C variant in the 5'-flanking region, which are not linked to each other. In our previous reports, we showed a positive association between the Glu298Asp variant and essential hypertension, myocardial infarction, and coronary spastic angina. We also revealed that the T-786-->C variant is strongly associated with coronary spastic angina and leads to the reduction of the eNOS gene promoter activity. To further investigate the genetic involvement of the eNOS gene in essential hypertension, we examined the frequency of T-786-->C variant in two independent populations of persons with essential hypertension in Kyoto (n=215) and Kumamoto (n=186) and compared the frequency with that in each age- and gender-matched control (233 controls in Kyoto and 223 controls in Kumamoto). In both groups, the frequency of T-786-->C variant was similar in patients with hypertension and normal controls. In conclusion, the T-786-->C variant was not positively associated with essential hypertension. Given the evidence of positive association of another polymorphism in the eNOS gene, the Glu298Asp polymorphism, with essential hypertension, special attention will be required to interpret the results of a case-control study for genetic risk factors.

Adult↗

Magnetic resonance coronary angiography in patients with ischemic heart disease: analysis of coronary arterial blood flow velocity pattern.

Only a few reports evaluating coronary arterial blood flow velocity patterns using magnetic resonance (MR) coronary angiography have appeared to date. This study reports an evaluation of coronary arterial blood flow velocity patterns in patients with ischemic heart disease and in healthy subjects using MR coronary angiography. The subjects consisted of 20 patients with ischemic heart disease (IHD group) and 20 normal healthy subjects (N group). Using the fCARD PC method, ECG-gated MR coronary angiography was performed using an anteroposterior opposing phased array coil. Regions of interest were placed on bilateral coronary arteries to measure coronary arterial blood flow velocity patterns. The IHD group was divided into two subgroups, based on the presence (MI group) or absence (AP group) of infarcted myocardium using 99m Tc-methoxyisobutylisonitrile (MIBI) myocardial scintigraphy. Average diastolic peak velocity (ADPV) was lower in the IHD group than in the N group. In addition, the diastolic / systolic velocity ratio (DSVR) was significantly lower in the MI group. Moreover, in the AP group, both the ADPV and DSVR values were significantly increased in those who had undergone percutaneous transluminal coronary angioplasty postoperatively. Different from the Doppler guidewire method, MR coronary angiography facilitates noninvasive evaluation of coronary arterial blood flow velocity. Therefore, these results indicate that MR coronary angiography represents a potentially useful technique for diagnosing lesions of coronary arteries and evaluating their functions. This noninvasive method can be expected to replace the invasive Doppler guidewire method in the near future with development of MR coronary angiography technology.

Aged↗

Effects of short-term pulmonary rehabilitation on exercise capacity and quality of life in patients with chronic obstructive pulmonary disease.

Although the rehabilitation of patients with chronic obstructive pulmonary disease (COPD) improves both exercise capacity and quality of life, a standard protocol for COPD patients has not been established. To clarify whether physiologic and quality-of-life improvements can be achieved by an inpatient pulmonary rehabilitation program 5 days per week for 3 weeks, 18 patients with COPD were enrolled in a rehabilitation program. The physical exercise training regimen consisted of respiratory muscle stretch gymnastics and cycle ergometer exercise training. Pulmonary function tests, an incremental ergometer exercise test, a 6-min walking test, and a quality of life assessment by the Chronic Respiratory Questionnaire were administered before and after the program. The peak VO2, an indicator of maximal exercise capacity, did not increase, although the 6-min walking distance, an indicator of functional exercise capacity, increased significantly after rehabilitation. There was a significant improvement in the quality of life in terms of dyspnea, fatigue, and emotional state. These findings suggest that even a 3-week program may be beneficial for COPD patients. Increases in functional exercise capacity, even without an increase in maximal exercise capacity, are helpful for reducing dyspnea and improving quality of life parameters in patients with COPD.

Aged↗

Estimation of the sporozoite rate of malaria vectors using the polymerase chain reaction and a mathematical model.

We developed a sensitive polymerase chain reaction (PCR) method for the detection of Plasmodium falciparum DNA from mosquitoes collected in the field. Plasmodium falciparum was detected from 15.2% of 1-parous mosquitoes, Anopheles farauti, in the Solomon Islands through use of the PCR method. A novel mathematical model was developed to estimate the sporozoite rate based on the malaria-positive rate of 1-parous mosquitoes. Using this model, the sporozoite rate of Anopheles farauti in the Solomon Islands was calculated to be 0.09%. This method enables estimation of the sporozoite rate based on a relatively small number (100-200) of mosquitoes compared with the number needed for the ELISA method.

Animals↗

Cardiorespiratory responses during cycle ergometer exercise with different ramp slope increments in patients with chronic obstructive pulmonary disease.

OBJECTIVE: The ramp exercise test has been widely used to evaluate cardiopulmonary responses to an incremental exercise load. This study was performed to clarify whether different slopes of the ramp exercise test influence exercise tolerance, exercise limiting factors, and respiratory pattern in patients with chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: We applied three different slopes (5 W/min, 10 W/min and 20 W/min) of the ramp exercise test in 9 patients with COPD and evaluated cardiopulmonary responses. RESULTS: There were no significant differences in peak oxygen uptake, anaerobic threshold (AT), minute ventilation, heart rate, arterial oxygen saturation, expired tidal volume, or respiratory rate at the maximal load among the three different ramp exercises tested. AT could be determined in six of nine patients (67%) at the slope of 5 W/min, in 8/9 (89%) at the slope of 10 W/min, and in 9/9 (100%) at the slope of 20 W/min. CONCLUSION: The findings suggest that the ramp slope does not affect exercise tolerance, exercise limiting factors, or respiratory patterns and each of these ramp slopes is useful for the evaluation of COPD. Ramp slopes of 10 W/ min or 20 W/min should be appropriate for the determination of AT.

Aged↗

Myositis as a manifestation of chronic graft-versus-host disease.

We report a 22-year-old man who had myositis in the course of chronic graft-versus-host disease after bone marrow transplantation for acute monocytic leukemia. The distribution of muscular involvement was different from idiopathic polymyositis. Muscular atrophy and weakness were noted in the distal muscles as well as in the proximal muscles of the upper extremities but there was little weakness in the proximal muscles of the lower extremities. However, histological and immunohistochemical study of the biceps brachii muscle showed findings similar to those of idiopathic polymyositis. It was suggested that myositis can be a manifestation of chronic GVHD caused by a cellular immune reaction by donor T cells.

Adult↗

2,3-Butanedione monoxime suppresses primarily total calcium handling in canine heart.

Whether 2,3-butanedione monoxime (BDM, < or = 5mmol/l) suppresses primarily crossbridge cycling or total Ca(2+) handling in the blood-perfused whole heart remains controversial. Although BDM seems to suppress primarily total Ca(2+) handling in canine hearts, more evidence is lacking. We therefore analyzed the cardiac mechanoenergetics, namely, E(max) (contractility), PVA (total mechanical energy), and O(2) consumption of canine BDM-treated hearts by our recently developed integrative method to assess myocardial total Ca(2+) handling. This method additionally required the internal Ca(2+) recirculation fraction. We obtained this from the beat constant of the exponential decay component of the postextrasystolic potentiation. Our analysis indicated significant decreases in both internal Ca(2+) recirculation fraction and total Ca(2+) handling in the BDM-treated heart, but virtually no change in the reactivity of E(max) to total Ca(2+) handling. This result corroborates the view that BDM suppresses primarily total Ca(2+) handling rather than crossbridge cycling in the canine blood-perfused heart.

Animals↗

Reactivation of human herpesviruses after allogeneic peripheral blood stem cell transplantation and bone marrow transplantation.

Reactivation of latent herpesviruses results in outcomes ranging from asymptomatic shedding of viruses to severe diseases, depending on the immunological competence of the host. Severe and prolonged suppression of cellular and humoral immunity after hematopoietic stem cell transplantation is accompanied by a high incidence of symptomatic recurrent herpesvirus infections. Subclinical reactivation also occurs more frequently than previously expected in transplant recipients. An increasing viral load in the blood detected by an antigenemia assay or PCR and viral shedding in regional fluids have a predictive value for subsequent diseases. Monitoring of viral DNA in the peripheral blood after allogeneic bone marrow transplantation (allo-BMT) reveals unique temporal profiles of detection for each herpesvirus. Recent studies demonstrate that recovery of CD4+ T cells is enhanced within one month after allogeneic peripheral blood stem cell transplantation (allo-PBSCT) compared to allo-BMT. To clarify whether this immunological advantage could affect the reactivation of human herpesvirus (HHV), we monitored the emergence of viral DNA by a nested-double polymerase chain reaction in peripheral blood leukocytes. Detection rates of HHV-6 DNAs which peak at 3-4 weeks post-transplant, were significantly reduced after allo-PBSCT compared to allo-BMT, while those of other herpesviruses which tend to be reactivated later than this period (Epstein-Barr virus and cytomegalovirus) were similar between the two types of transplants. Detection of HHV-6 DNA within the first month after the transplant was associated with delayed platelet engraftment. These results underscore the important role of CD4+ T reconstitution in inhibiting virus reactivation post-transplant.

Bone Marrow Transplantation↗

Human T-lymphotropic virus type I provirus and T-cell prolymphocytic leukemia.

T-cell prolymphocytic leukemia (T-PLL) is a rare type of post-thymic T-cell neoplasm, the etiology of which is unknown. Patients with T-PLL have been found to be seronegative for human T-lymphotropic virus type-I (HTLV-I), and their leukemia cells do not retain monoclonally integrated HTLV-I provirus. Recently, we have demonstrated the presence of defective HTLV-I provirus by polymerase chain reaction in the DNA extracted from peripheral blood cells or affected lymph nodes of T-PLL patients. Although there is a possibility, from our observation, that an alternative mechanism is operating in HTLV-associated leukemogenesis, it is still unknown whether and how HTLV-I can contribute to the leukemogenesis of T-PLL. In this review, we describe controversial issues and discuss a role of HTLV-I in the leukemogenesis of T-PLL.

Cell Transformation, Viral↗

Antitumor activity of interleukin-12 against murine bladder cancer.

PURPOSE: We investigated the antitumor activity of interleukin-12 (IL-12) against MBT-2, a murine bladder carcinoma, to clarify whether or not IL-12 is effective against urothelial tumors. MATERIALS AND METHODS: MBT-2, a murine carcinogen-induced, poorly differentiated transitional cell carcinoma of C3H/He origin, was used. Three or 10 days after the subcutaneous administration of MBT-2 cells, C3H/He mice were injected intraperitoneally with IL-12 five times per wk. for 2 wk. Tumor growth was measured twice weekly. Spleen cells from the C3H/He mice that had rejected MBT-2 after the IL-12 treatment were examined for MBT-2-specific cytolytic T lymphocytes (CTL) activity and cytokine production. RESULTS: Tumor growth and acceptance was obviously suppressed when C3H/He mice were treated with IL-12 from 3 days after the tumor inoculation. In the spleen cells from the C3H/He mice that had rejected MBT-2, MBT-2-specific CTL activity and secretion of IL-2 and interferon (IFN)-gamma were clearly detected. However, the established MBT-2 tumor cells were not rejected when C3H/He mice were given IL-12 from 10 days after the tumor inoculation, although the tumor growth was transiently suppressed during the IL-12 treatment. CONCLUSION: These data demonstrate that IL-12 is considerably effective against murine bladder cancer and suggest the clinical application of IL-12 against human bladder cancer.

Adjuvants, Immunologic↗

Granulocyte colony-stimulating factor and lineage-independent modulation of VLA-4 expression on circulating CD34+ cells.

Although the use of allogeneic transplants of peripheral blood stem/progenitor cells (PBSCs) is increasing, the precise mechanism of PBSC mobilization has not yet been fully clarified. We examined the expression of some adhesion molecules on CD34+ cells from steady-state bone marrow (BM), granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCs, and cytotoxic drugs plus G-CSF-mobilized PBSCs. Irrespective of mobilization method, very late antigen (VLA)-4 expression on circulating CD34+ cells was significantly lower than on steady-state BM CD34+ cells. To elucidate the influence of lineage commitment on VLA-4 expression of circulating CD34+ cells, we analyzed VLA-4 expression on different subsets of CD34+ cells with or without CD33, CD38, CD5, or CD10 antigens, or Glycophorin A in G-CSF-mobilized PBSCs and steady-state BM from related donors, using 3-color flow cytometry. VLA-4 on circulating CD34+ subsets was less expressed than on each corresponding subset of steady-state BM CD34+ cells. Furthermore, VLA-4 positive rates showed no significant difference among the CD34+ subsets. Finally, the data comparing CD34+ cells from steady-state and G-CSF-mobilized PBSCs revealed no differences in terms of VLA-4 expression. These data suggest that reduced expression of VLA-4 may be a result of peripheralization of CD34+ cells from bone marrow, which occurs in a G-CSF- and lineage-independent fashion.

Anti-Allergic Agents↗

[Clinical evaluation of the diagnosis of neuronal reversibility with acute cerebral infarction using ADC by diffusion weighted echo planar imaging].

The possibility of diagnosing neuronal reversibility with acute cerebral infarction was studied using ADC measured by diffusion weighted imaging (DWI). The subjects were eleven patients who underwent DWI within 24 hours of onset. The area of abnormal signal on DWI during the acute stage was visually compared with that on T2-WI in the subacute phase. ADC was calculated in the two different abnormal areas on DWI, which were differentiated by the presence or absence of abnormality on T2-WI in the subacute phase. The abnormal signals of three cases showed an obviously narrowed area on DWI in the acute phase compared with the abnormality on T2-WI in the sub-acute phase. ADCs of the ischemic areas in DWI abnormalities that showed no abnormality on subacute T2-WI were slightly higher than those of the infarct areas with remaining abnormal signals on T2-WI. However, no statistically significant difference was found between these two regions, because there were large variations within each pixel. We considered that the diagnosis of neuronal reversibility in acute cerebral infarction was difficult using ADC values only and that other parameters such as perfusion or blood volume will be necessary to improve diagnostic quality prior to determining therapy.

Acute Disease↗

Inhibition of disease flare with diethylstilbestrol diphosphate and chlormadinone acetate administration for two weeks prior to slow-releasing leuprolide acetate in prostatic cancer patients.

To determine whether administration of estrogen or gestagen prior to luteinizing hormone-releasing hormone (LH-RH) agonist prevents disease flare in prostate cancer patients, we pretreated the patients with either diethylstilbestrol diphosphate (DES-P) 300 mg daily (N = 17) or chlormadinone acetate (CMA) 100 mg daily (N = 16) or none (N = 16) for two weeks before the initial injection of leuprolide acetate (L). Blood samples for prostatic specific antigen (PSA), testosterone (T), and luteinizing hormone were collected before CMA and DES-P administration, before and at 2, 7, 14, 28, 56, and 84 days after the first administration of leuprolide. The treatment with DES-P and CMA prior to LH-RH agonist induced an early decline of PSA. The mean PSA level showed no significant secondary rise in those patients with pretreatment after L administration. In the patients pretreated with DES-P or CMA, the mean serum T level never exceeded the pretreatment baseline after L administration. On the other hand, in the patients without DES-P or CMA, both serum T and PSA levels increased after the first administration of L. These results clearly demonstrate that pretreatment with DES-P 300 mg daily or CMA 100 mg daily for 2 weeks is quite effective to prevent disease flare after the first administration of L in patients with prostatic cancer.

Aged↗

Hepatocellular carcinoma with extension into the right atrium: report of a successful liver resection by hepatic vascular exclusion using cardiopulmonary bypass.

We report a successful liver resection using cardiopulmonary bypass with, total hepatic vascular exclusion (THVE) for hepatocellular carcinoma (HCC), with extension into the right atrium. A 61-year-old man with a cirrhotic liver was referred to our department with HCC in the medial segment of the left lobe of the liver, and tumor thrombus extending into the right atrium. During surgery, a left lobe and caudate lobe of the liver were transected leaving the left lobe of the liver connected to the inferior vena cava (IVC) by only the left and middle hepatic trunks, and then the intracaval tumor thrombus and the left lobe of the liver were removed en bloc using cardiopulmonary bypass with total hepatic vascular exclusion (THVE). Cardiac arrest was not performed during THVE, and the patient had an uneventful postoperative course and was discharged from the hospital 2 months following surgery. He died of multiple pulmonary metastases 4 years and 8 months after surgery; however, imaging showed no evidence of recurrence in the remnant liver during that period. In conclusion, by performing dissection of the hepatic parenchyma to the hepatic vein prior to removal of the tumor thrombus, the period of extracorporeal circulation, duration of warm ischemic time to the liver, and intraoperative blood loss were all reduced and a radical operation could be performed safely without scattering tumor cells during extirpation of the tumor.

Carcinoma, Hepatocellular↗

How to spread out the satisfactory exposure: placement technique in right-sided maze procedure.

We have, whenever possible, substituted cryoablation for incisions in the maze procedure. Cryoablation helps prevent massive bleeding because the number of resuturing sites is reduced and aortic cross-clamp time decreased. We are careful not to injure the atrio-ventricular conduction system during incision at the side of the Koch triangle or cryoablation while manipulating the atrial septum. In prior versions of the right-sided maze procedure, the IVC return cannula has obstructed the surgical field approaching the IVC and the tricuspid valve annulus. This report describes a new modification of maze procedure that includes changing the venous return site. We have obtained a satisfactory surgical field without being afraid of the anatomical pitfall, between the appendage and the tricuspid valve, and between the right coronary artery and the extended T incision. We studied 12 patients (8 males and 4 females, mean age 61 years) who underwent the maze procedure. Sinus rhythm was restored in 11 patients, whose clinical condition was improved to NYHA class I status. This technique has proven effective in obtaining satisfactory exposure of the-right atrium during the maze procedure.

Aged↗