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Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 55 records · Page 3Linked to original sources
PubMed2004

Excess accumulation of body fat is related to dyslipidemia in normal-weight subjects.

OBJECTIVE: To assess the relationship of fat mass (FM) and its distribution to hypertension and dyslipidemia in normal-weight Japanese individuals. DESIGN: Cross-sectional study. SUBJECTS: Apparently healthy Japanese subjects with a body mass index (BMI) between 20 and 23.5 kg/m(2) (265 males and 741 females, age 21-69 y). MEASUREMENTS: BMI, waist circumference (WC), waist-hip ratio (WHR), systolic and diastolic blood pressure, serum levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) were measured. Low-density lipoprotein-cholesterol (LDL-C) was calculated by the Friedewald formula. Percentage fat mass (%FM) and trunk fat mass-leg fat mass ratio (FM(trunk)/FM(legs)) were obtained by dual-energy X-ray absorptiometry. RESULTS: WC, WHR, %FM and FM(trunk)/FM(legs) were significantly correlated with TC, LDL-C, HDL-C and TG with the tendency of FM(trunk)/FM(legs) to show the strongest correlations. For %FM and FM(trunk)/FM(legs) in both sexes, odds ratios (ORs) of the third tertiles with respect to the first tertiles increased for LDL-C elevation, TG elevation and dyslipidemia. In males, ORs of the third tertiles of WC were significantly high for LDL-C elevation and dyslipidemia whereas those of WHR were high for TG elevation and dyslipidemia. ORs of the third tertiles of WC and WHR were significantly high for TG elevation in females. BMI was not associated with the risk of abnormal lipid levels. ORs for hypertension showed significant increases in none of the variables of obesity. CONCLUSIONS: Excess accumulation of FM, especially to the upper body, was related to dyslipidemia in normal-weight subjects. Simple anthropometric variables, WC and WHR, may be useful for screening and management of dyslipidemia in these subjects.

Absorptiometry, Photon↗
PubMed2004

Longevity-associated mitochondrial DNA 5178 A/C polymorphism and blood pressure in the Japanese population.

It has been reported that the mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism, also called NADH dehydrogenase subunit 2-237 methionine/leucine (ND2-237 Met/Leu) polymorphism, may be associated with longevity in Japanese individuals, and that the mt5178A genotype may have an antiatherogenic influence. To determine whether mt5178 A/C polymorphism influences blood pressure, we genotyped 412 healthy Japanese individuals and performed a cross-sectional study investigating the relationship between genotype and blood pressure. In women with mt5178A, the mean diastolic blood pressure was higher than in those with mt5178C by 3.2 mmHg (P=0.040). In men, no statistically significant difference in systolic or diastolic blood pressure was observed between mt5178 A/C genotypes. However, a significant correlation between mt5178 A/C genotypes and the effects of habitual drinking on blood pressure was found. After adjustment for several factors, in men carrying mt5178C, both systolic and diastolic blood pressure were significantly higher in daily drinkers than in occasional (P=0.002 and 0.002, respectively) as well as nondrinkers (P<0.001 and 0.001, respectively), whereas in men carrying mt5178A, no significant differences in blood pressure were detected, irrespective of alcohol consumption. These results suggest that mt5178 A/C (=ND2-237 Met/Leu) polymorphism may influence both diastolic blood pressure in Japanese women and the blood-pressure-increasing effect of drinking in Japanese men.

Alcohol Drinking↗
PubMed2004

Absence of association between the MCP-1 gene polymorphism and histological phenotype of lupus nephritis.

Lupus nephritis presents two polar histological patterns, diffuse proliferative glomerulonephritis (DPGN) and membranous glomerulonephritis (MGN). In the kidney tissue of DPGN, numerous mononuclear cells were seen in the interstitium and glomeruli; on the other hand in MGN, infiltrating cells were less frequent. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant for monocytes, T-cells, and natural killer cells. In this study we assessed the significance of the MCP-1 gene in determination of the histological phenotype in lupus nephritis. There was no association between the risk of DPGN and the MCP-1 gene genotype.

Adolescent↗
PubMed2004

Treatment of supracondylar fracture of the humerus in children by skeletal traction in a brace.

In 1980, we developed a specially designed brace for treating supracondylar fractures of the humerus in children, along with an easy and safe technique of reduction by skeletal traction. This method, which takes into consideration only the medial tilting and anterior angulation of the distal fragment, achieves complete reduction, ignoring any lateral, posterior and minor rotational displacements of the fragment. Skeletal traction is applied through a screw inserted into the olecranon and the angulation at the fracture site is reduced regardless of the anatomical position without manipulation. We treated 193 children with displaced supracondylar fractures of the humerus using this method between 1980 and 2001. Only four children (2%) developed cubitus varus. The majority obtained an excellent range of movement at the elbow; one had a 25 degree limitation of flexion. This technique is an effective and easy method of treating supracondylar fractures of the humerus in children.

Braces↗
PubMed2004

[Aortic regurgitation due to nonpenetrating trauma of the chest; report of a case].

A 64-year-old man was admitted to our hospital with multiple traumas, caused by motorcycle accident. Six months later, he revisited our hospital, because he was found to have aortic regurgitation and subsequent congestive heart failure. Therefore, the aortic valve was excised and replaced with 23 mm CarboMedics prosthesis. His postoperative course was uneventful. Aortic regurgitation due to nonpenetrating trauma of the chest is rare.

Accidents, Traffic↗
PubMed2004

[Lobectomy for lung cancer in an elderly man on maintenance hemodialysis].

An 82-year-old man who had been undergoing hemodialysis for chronic renal failure, 3 times a week for the last 3 years, was admitted to our hospital for the treatment of lung cancer. Under careful perioperative management, we successfully performed a lobectomy. Histological examination revealed well differentiated squamous cell carcinoma and the postoperative staging was pT1N0M0. On postoperative day 1, he was commenced on hemodialysis with nafamostat mesilate instead of heparin sodium, and there was no postoperative bleeding. The patient had an uneventful postoperative course and was discharged 3 weeks after his operation.

Aged↗
PubMed2003

Phase I/II study of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer.

Recent studies have suggested the superiority of concomitant over sequential administration of chemotherapy and radiotherapy. Docetaxel and cisplatin have demonstrated efficacy in advanced non-small-cell lung cancer (NSCLC). This study evaluated the safety, toxicity, and antitumour activity of docetaxel/cisplatin with concurrent thoracic radiotherapy for patients with locally advanced NSCLC. Patients with locally advanced NSCLC (stage IIIA or IIIB), good performance status, age or=3 toxicities of 71, 60, 24, and 19%, respectively. Toxicity was significant, but manageable according to the dose and schedule modifications. Dose intensities of docetaxel and cisplatin were 86 and 87%, respectively. Radiotherapy was completed without a delay in 67% of 42 patients. The overall response rate was 79% (95% confidence interval (CI), 66-91%). The median survival time was 23.4+ months with an overall survival rate of 76% at 1 year and 54% at 2 years. In conclusion, chemotherapy with cisplatin plus docetaxel given on days 1, 8, 29, and 36 and concurrent thoracic radiotherapy is efficacious and tolerated in patients with locally advanced NSCLC and should be evaluated in a phase III study.

Adult↗
PubMed2003

Acute lymphoblastic leukemia with large molecular ACTH production.

Ectopic hormone production is very rare in hematological malignancy. Here, we describe an interesting case of acute lymphoblastic leukemia (ALL) with adrenocorticotropic hormone (ACTH) production. A 47-year-old man was admitted to our hospital with a 7-month history of hyperpigmentation. The plasma level of ACTH was markedly elevated without a circadian rhythm and the level of cortisol was normal. Examination of bone marrow aspiration revealed ALL, and no other disease as a cause of the elevated ACTH was detected. Sephadex G-75 chromatography of plasma ACTH extract revealed the existence of an abnormally large molecular ACTH (probably proopiomelanocortin) in addition to authentic 1-39 ACTH. Ectopic ACTH of low biological activity is considered to be the reason for a discrepancy in the plasma levels of ACTH and cortisol. Shortly after remission induction chemotherapy, blast cells in the peripheral blood disappeared, and the plasma level of ACTH became normal, leading to an improvement of skin pigmentation. These clinical findings and laboratory data suggested that leukemia cells in this case may produce the ACTH.

Adrenocorticotropic Hormone↗
PubMed2003

Diagnosis of acute brain-stem infarcts using diffusion-weighed MRI.

There are many reports on acute cerebral infarcts diagnosed by diffusion-weighted MRI (DWI), but few describe brain-stem infarcts diagnosed by this method. Using the apparent diffusion coefficient (ADC), we studied 18 consecutive patients with brain-stem infarcts who underwent DWI during the acute phase. We calculated and compared the ADC ratio (lesion ADC/contralateral ADC) in 10 patients with brain-stem and 23 with supratentorial cortical infarcts examined within 24 h of the onset of stroke. Ischaemic brain-stem lesions were detected in all 15 patients who underwent DWI more than 3 h after the onset, but not in two who had DWI within 3 h of the onset; their ADC ratio was more than 0.95. ADC ratios in patients with brain-stem infarcts decreased as the interval between onset and DWI increased; the decrease was slower than in patients with supratentorial cortical infarcts.

Acute Disease↗
PubMed2003

A novel polymorphism of the human APRIL gene is associated with systemic lupus erythematosus.

OBJECTIVE: We investigated the association of gene polymorphisms in APRIL, a new member of the TNF family, with systemic lupus erythematosus. METHODS: To detect polymorphisms of the human APRIL gene by exon-specific polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis, we first determined the structure of the human APRIL gene. We designed exon-specific oligonucleotide primers according to the genomic DNA sequence of APRIL. All of the coding regions in exons of the APRIL gene were analysed by exon-specific PCR-SSCP in 148 SLE patients and 146 unaffected controls, then the nucleotide sequences of exons that displayed aberrant bands were determined. RESULTS: The human APRIL gene comprised at least six exons with five introns, spanning approximately 2.8 kilobases of the genomic DNA. By exon-specific PCR-SSCP, we identified two novel polymorphisms at codons 67 and 96. Both had amino acid substitutions: G67R and N96S respectively. Only the 67G allele was associated with SLE in 148 Japanese SLE patients, with allele frequency 0.662 compared with 0.575 for 146 unaffected controls (P=0.0302). The frequency of the individuals who possessed at least one 67G allele in SLE patients (91.9%) was significantly higher than that in the unaffected controls (80.1%) (P=0.0036). CONCLUSION: The 67G allele of APRIL may be a contributing factor in the pathogenesis of SLE.

Adolescent↗
PubMed2003

Plasma stromal cell-derived factor-1 during granulocyte colony-stimulating factor-induced peripheral blood stem cell mobilization.

In this report, we examined plasma stromal cell-derived factor-1 levels in normal healthy donors for allogeneic peripheral blood stem cell transplantation (PBSCT) and in patients for autologous PBSCT using an enzyme-linked immunosorbent assay. The average level of plasma stromal cell-derived factor-1 was 2197 pg/ml before granulocyte colony-stimulating factor administration and 1899 pg/ml on day 4, demonstrating a significant decrease in the peripheral blood of healthy donors (P=0.0003). In patients for autologous PBSCT, a significant decrease of plasma stromal cell-derived factor-1 in the peripheral blood was also observed (P=0.0464). However, the physiologic gradient of stromal cell-derived factor-1 between peripheral blood and bone marrow was never inverted in normal healthy donors or in autologous PBSCT patients. Our results suggest that stromal cell-derived factor-1 may not be involved in the granulocyte colony-stimulating factor-induced release of CD34(+) cells to the peripheral blood. Further studies of a possible additive effect of granulocyte colony-stimulating factor and stromal cell-derived factor-1 are warranted.

Adult↗
PubMed2003

Influence of transplanted dose of CD56+ cells on development of graft-versus-host disease in patients receiving G-CSF-mobilized peripheral blood progenitor cells from HLA-identical sibling donors.

We investigated effects of variations in the cellular composition of G-CSF-mobilized peripheral blood progenitor cell (G-PBPC) allografts on clinical outcomes of allogeneic PBPC transplantation. We retrospectively analyzed transplanted doses of various immunocompetent cells from 27 HLA-identical sibling donors in relation to engraftment, incidence of graft-versus-host disease (GVHD), and survival. Significant variability was documented in both absolute numbers and relative proportions of CD34+, CD2+, CD3+, CD4(high)+, CD4+25+, CD8(high)+, CD19+, CD56+, and CD56+16+ cells contained in these allografts. Stepwise Cox regression analysis revealed that the CD56+ cell dose was significantly inversely correlated with the incidence of GVHD. Thus, there was a significantly higher incidence of grade II acute GVHD in patients receiving a lower CD56+16+ cell dose (hazard ratio (HR) 0.0090; 95% confidence interval (CI), <0.00001-3.38; P=0.031), a higher incidence of chronic GVHD in those receiving allografts with a lower CD56+16+ to CD34+ ratio (HR <0.00001; 95% CI <0.00001-0.0007; P=0.0035), and a higher incidence of extensive chronic GVHD in those receiving allografts with a lower CD56+ to CD34+ ratio (HR <0.00001; 95% CI <0.00001-0.053; P=0.0083). These results suggest that CD56+ cells in G-PBPC allografts from HLA-identical sibling donors may play an important role in preventing the development of GVHD.

Adult↗
PubMed2003

Detection of cardiovascular risk factors by indices of obesity obtained from anthropometry and dual-energy X-ray absorptiometry in Japanese individuals.

OBJECTIVE: To determine the cut-off points of indices of obesity for detecting hypertension, dyslipidemia and diabetes mellitus in Japanese individuals. DESIGN: Cross-sectional study. SUBJECTS: A total of 2728 Japanese individuals (768 males and 1960 females, aged 20-79 y) who attended the Fukuoka Health Promotion Center, Japan for health check-up. MEASUREMENTS: Body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR) were measured. Percentage fat mass (%FM), trunk fat mass (FM(trunk)) and trunk fat mass-leg fat mass ratio (FM(trunk)/FM(legs)) were obtained by dual-energy X-ray absorptiometry (DXA). Cardiovascular risk factors were determined by blood pressure, serum lipids, fasting blood glucose and hemoglobin A(1C). RESULTS: The cut-off points of BMI, WC and WHR were around 23.5 kg/m(2), 84 cm and 0.9 for males, and 22.5 kg/m(2), 72 cm and 0.8 for females. The cut-off points of %FM, FM(trunk) and FM(trunk)/FM(legs) were around 24%, 8 kg and 1.6 for males, and 35%, 9 kg and 1.4 for females. WHR and FM(trunk)/FM(legs) most accurately detected the risk factors. CONCLUSIONS: For Japanese individuals, the cut-off points for detecting cardiovascular risk factors are lower than the criteria by the World Health Organization. Indices of fat distribution detected the cardiovascular risk factors more accurately than those of overall adiposity. The accuracy of detecting the risk factors was comparable between the anthropometric indices and indices obtained by DXA.

Absorptiometry, Photon↗
PubMed2003

In vitro expansion of human basophils by interleukin-3 from granulocyte colony-stimulating factor-mobilized peripheral blood stem cells.

BACKGROUND: A number of studies support the belief that human basophils play an important role in allergic inflammation. The exact mechanism of basophil activation at the site of allergic inflammation, however, has not been well understood, mainly due to their low number in blood and difficulty in obtaining a sufficient number of highly purified basophils for investigation. OBJECTIVE: The purpose of this study is to expand human basophils in vitro with high yield and purity by culturing peripheral blood stem cells (PBSCs). METHODS: We collected PBSC-rich mononuclear cells containing CD34+ cells (0.15-4.9%) by leukapheresis from patients with malignant lymphoma and lung cancer during haematopoietic recovery after chemotherapy plus granulocyte colony-stimulating factor-induced mobilization. PBSC-rich mononuclear cells were cultured in the presence of IL-3. RESULTS: When PBSC-rich mononuclear cells containing more than 1% of CD34+ cells were cultured, 20.0-83.3% of the cells, mostly with a yield of >10%, were metachromatic cells after 3 weeks of culture. These cells resembled mature peripheral blood basophils morphologically when examined by light and electron microscopy. Flow cytometric analysis showed that they expressed both FcepsilonRI and FcgammaRII. FcepsilonRI cross-linking resulted in intracellular calcium mobilization, histamine release and synthesis of cysteinyl leukotrienes. The intracellular histamine content and the release of these chemical mediators triggered by anti-IgE antibodies were comparable to those of peripheral blood basophils. CONCLUSION: These findings suggest that PBSC-derived basophils expanded in vitro are morphologically and functionally mature and will be a useful tool for the analysis of basophil functions.

Adolescent↗
PubMed2003

Pharmacokinetics and metabolism of NO-1886, a lipoprotein lipase-promoting agent, in cynomolgus monkey.

1. The study was conducted to investigate the pharmacokinetics and metabolism of NO-1886 (diethyl 4-[(4-bromo-2-cyanophenyl) carbamoyl] benzylphosphonate) in cynomolgus monkeys. 2. After single intravenous administration of NO-1886 at a dose of 3 mg kg(-1), the total clearance (CL(tot)), area under the plasma concentration-time curve (AUC(0-)(t)), half-life (t(1/2)), and volume of distribution (V(d)) in cynomolgus monkeys were 531 ml h(-1) kg(-1), 5.63 micro g h ml(-1), 0.96 h and 679 ml kg(-1), respectively. The AUC(0-)(t) for oral administration of NO-1886 (3 mg kg(-1)) was 4.23 micro g h ml(-1) and the bioavailability was 75%. 3. M-2 (ethyl 4-[(4-bromo-2-cyanophenyl) carbamoyl] benzylphosphonate) and M-3 (4-[(diethoxy-phosphoryl) methyl)] benzoic acid) were present as metabolites in plasma and urine. In faeces, M-2 was present but M-3 was not. 4. The major metabolite of NO-1886 in liver S9 or microsomes was M-2 in the presence of NADPH. On the other hand, M-3 was formed in the absence of NADPH in liver S9 or microsomes and its formation was inhibited by bis-( p-nitrophenyl) phosphate (BNPP) in liver S9, suggesting that the formation of M-3 was catalysed by carboxylesterase. 5. The findings suggest that the main metabolic pathway of NO-1886 in cynomolgus monkeys is the O-deethylation of NO-1886 to M-2, as in rats and humans, and that the hydrolysis of the amide bond is a minor metabolic pathway.

Administration, Oral↗
PubMed2002

UDP-Gal: betaGlcNAc beta1, 3-galactosyltransferase, polypeptide 3 (GALT3) is a tumour antigen recognised by HLA-A2-restricted cytotoxic T lymphocytes from patients with brain tumour.

Patient prognosis in the case of malignant brain tumours is generally poor, despite significant improvements in the early detection of the tumours, and thus the development of new treatment modalities is needed. One of the most prominent modalities is specific immunotherapy, for which the elucidation of antigenic molecules of malignant brain tumours recognized by T cells is essential. We report here a gene, UDP-Gal: betaGlcNAc beta1, 3-galactosyltransferase, polypeptide 3, encoding three epitope peptides recognised by tumor-reactive cytotoxic T lymphocytes in an HLA-A2-restricted manner. Two of the three peptides possessed an ability to induce HLA-A2-restricted and tumour-reactive cytotoxic T lymphocytes from peripheral blood mononuclear cells of patients with brain tumours. These peptides may be useful in the peptide-based specific immunotherapy for patients with malignant brain tumours.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed2002

High-dose chemotherapy and autologous peripheral blood stem cell transplantation for treatment of unspecified peripheral T-cell lymphoma presented with hepatosplenomegaly and hypercytokinemia syndrome: report of three cases.

We report here three cases of peripheral T-cell lymphoma unspecified (PTCL-US), which presented with bone marrow infiltration and hepatosplenomegaly and were successfully treated with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (auto-PBSCT). The patients were all characterized by cytokine-induced symptoms such as fever, anasarca, cytopenia, poor general condition, and disseminated intravascular coagulation syndrome. Laboratory data showed extremely high levels of soluble interleukin-2 receptor, beta(2)-microglobulin, and ferritin. All three patients were negative for anti-adult T-cell leukemia antibody. In one patient, hemophagocytosis was revealed by a histological examination of the bone marrow. The International Prognostic Index was high for all three patients, and they all achieved complete remission after the intensive chemotherapy for remission induction. During complete remission, they were treated with HDCT [modified interleukin-converting enzyme regimen] followed by auto-PBSCT. The recovery of hematopoiesis after auto-PBSCT was prompt and sustained engraftment was obtained. No serious adverse effects other than myelosuppression were noted. One patient died due to cerebrovascular disease without relapse 18 months after auto-PBSCT. The other two patients are still alive and have not suffered from relapse. Our observations suggest that auto-PBSCT following HDCT may be an effective and safe therapeutic modality for high-risk PTCL-US patients characterized by hepatosplenomegaly and cytokine-induced syndrome.

Aged↗