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M Harada

Publications and source records attributed to M Harada.

At least 577 records · Page 32Linked to original sources
PubMed1995

Reduced N-acetylaspartate in the brain observed on in vivo proton magnetic resonance spectroscopy in patients with mental retardation.

Volume-selective proton magnetic resonance spectroscopy (1H-MRS) of the brain was performed with a 1.5T magnet in 28 patients with unclassified mental retardation (MR) and in 25 age-matched healthy children. Peaks of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr), but not of lactate, were observed in both groups on 1H-MRS. In all our subjects of this age range, 1H-MRS revealed an increase with advancing age in the ratio of NAA/Cho (P = .0031), but no developmental change in the NAA/Cr and Cho/Cr ratios. The NAA/Cho ratio was lower in patients with MR than in controls (P = .0016). The NAA/Cr ratio tended to be lower in the MR group, and the Cho/Cr ratio did not differ between patients with MR and controls. These results suggest that in patients with MR, NAA decreases and a disorder and/or dysfunction of neurons in the brain exists.

Adolescent↗
PubMed1995

Allogeneic peripheral blood stem cell transplantation for treatment of induction failure in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia.

We report a successful case of allogeneic peripheral blood stem cell transplantation (PBSCT) for the treatment of primary induction failure in acute lymphoblastic leukemia (ALL). The patient was a 46-year-old male with Ph-positive ALL and failed to achieve complete remission (CR). His HLA genotypically identical brother refused to donate bone marrow. Instead, PBSCs were collected by apheresis from the brother after administration of G-CSF at a dose of 10 micrograms/kg. For allogeneic PBSCT, the patient was conditioned with marrow ablative chemotherapy and received the PBSC harvest containing 7.8 x 10(4)/kg of CFU-GM, 1.8 x 10(6)/kg of CD34-positive cells and 2.7 x 10(8)/kg of T lymphocytes. After transplant, the neutrophil count exceeded 0.5 x 10(9)/l on day 16 and the platelet count exceeded 20 x 10(9)/l on day 22. CR was confirmed with tri-lineage engraftment in bone marrow samples on days 28 and 49; disappearance of the Ph-chromosome was documented. Sustained engraftment was also confirmed cytogenetically using a variable number of tandem repeat (VNTR) markers. Acute graft-vs.-host disease did not develop with conventional prophylaxis of methotrexate and cyclosporine. However, on day 85 the patient developed leukemia relapse and died on day 97. This clinical trial suggests that allogeneic PBSCT may be an alternative to allogeneic bone marrow transplantation in some limited situations.

Hematopoietic Stem Cell Transplantation↗
PubMed1995

Anti-metastatic activity induced by the in vivo activation of purified protein derivative (PPD)-recognizing Th1 type CD4+ T cells.

The Th1 type Cd4+ T cell clone (MH2), which is capable of recognizing purified protein derivative from Mycobacterium tuberculosis (PPD), was examined for its anti-metastatic activity against melanoma. In using an in vitro proliferative assay, MH2 was able to recognize PPD-derived antigen in a major histocompatibility complex class II-restricted manner. MH2 showed neither any natural killer (NK) activity nor cytolytic activity against syngeneic B16 melanoma. This clone produced interferon-gamma, tumor necrosis factor and interleukin-2, but not interleukin-4, when co-cultured with PPD and irradiated syngeneic C57BL/6 spleen cells, suggesting that this clone could thus be assigned to the Th1 subset. An intraperitoneal (i.p.) co-injection of 2 x 10(6) MH2 and 50 micrograms PPD increased the NK activity of the peritoneal exudate cells (PEC) and the percentage of NK1.1+ cells in the PEC. These activated NK cells showed a low but significantly cytolytic activity against B16 melanoma. The augmented NK activity induced by the co-injection of MH2 and PPD was maintained by the weekly additional i.p. injections of PPD alone. Using a murine metastatic model, and i.p. co-injection of MH2 and PPD-induced anti-metastatic activity against B16 melanoma. This anti-metastatic activity was then abrogated by the in vivo administration of anti-asialo GM1 serum. In addition, the NK activity in both peripheral blood and metastatic lungs was significantly augmented in the mice which were co-injected with MH2 and PPD. Taken together, these findings indicate that the in vivo activation of Th1 type CD4+ T cells augmented the NK activity in vivo and thus could potentially be an efficient immunotherapeutic weapon against metastasis of melanoma. These results also imply that adoptive immunotherapy could induce anti-metastatic activity through cytokine production but not through any direct cytolytic activity.

Adjuvants, Immunologic↗
PubMed1995

Intravascular hyperthermia: experimental study of transcatheter treatment.

RATIONALE AND OBJECTIVES: External hyperthermia has frequently been used to treat superficial malignant tumors. We postulated that transarterial internal hyperthermia may be effective for deeply located hypervascular tumors. We performed intravascular hyperthermia (IVH) for malignant hypervascular tumors that were transplanted into animals and evaluated the resulting histologic changes and antitumoral effects. METHODS: We designed a special catheter to heat the injected saline. Sixteen rabbits with hypervascular VX2 tumors ranging from 2 to 2.5 cm in diameter in their left hindlimb muscles served as subjects. IVH was performed via the left femoral artery (temperature = 50 degrees C) in 11 rabbits. Two sessions of IVH were performed during 1 week. Two weeks after the two sessions of IVH, the rabbits were sacrificed and their tumors and feeding arteries were resected. Five control rabbits had 37 degrees C saline infused using the same technique. RESULTS: The temperature in the central zone of the tumor increased markedly to 42.3 +/- 0.5 degrees C (mean +/- standard deviation), compared with 40.3 +/- 0.4 degrees C and 39.2 +/- 0.5 degrees C in the peripheral zones of the tumor and the surrounding tissue, respectively. Tumor sizes were calculated on angiograms as having decreased by 63 +/- 35% of their initial sizes during the 2 weeks after the two IVH sessions. However, tumor sizes increased to 171 +/- 41% in the control group (p < .01). Necrosis in the peripheral zones of the tumors in the IVH group was more severe than that in the control group (p < .05). Necrosis in the central zones of the tumors in the IVH group was slightly more severe. The surrounding tissue was not damaged. Although the femoral artery was not severely damaged, there was severe damage to the feeding arteries. CONCLUSION: IVH reduced the size of hypervascular tumors in our rabbits. The antitumoral effects are attributed to direct damage of the tumor vessels and to the effect of heat on the tumor cells.

Adenocarcinoma↗
PubMed1995

Transforming growth factor-alpha in human submandibular gland and saliva.

A sensitive sandwich enzyme immunoassay (EIA) for transforming growth factor-alpha (TGF-alpha) utilizing a polyclonal antibody that recognizes limited epitopes of both human TGF-alpha and rat TGF-alpha in combination with a monoclonal anti-TGF-alpha IgG1 galactosidase conjugate was developed. This assay shows no cross-reactivity with human epidermal growth factor. We can quantify the TGF-alpha level in not only human TGF-alpha (detection limit: 1 pg/ml), but also rat TGF-alpha (detection limit: 10 pg/ml) by virtue of cross-reactivity. Employing this assay system, we demonstrated that TGF-alpha is present in both human submandibular glands and submandibular/sublingual saliva.

Animals↗
PubMed1995

ATP-hydrolyzing excitation state of the reconstituted alpha 3 beta 3 complex of ATP synthase from the thermophilic bacterium PS3: structural characteristics shown by time-resolved small-angle X-ray scattering with synchrotron radiation.

The ATP-hydrolyzing excitation state of the alpha 3 beta 3 complex of the ATP synthase from the thermophilic bacterium PS3 was investigated using time-resolved small-angle X-ray scattering with synchrotron radiation. The results showed the presence of the alpha 3 beta 3 complex at a steady state during ATP hydrolysis when the alpha 3 beta 3 hexamer reacted with Mg-ATP. The radius of gyration of the complex in the steady state was significantly larger than that of the Mg-AMP-PNP-hexamer complex, indicating a conformational change to an expanded structure during catalysis. This alpha 3 beta 3 complex dissociated into alpha 1 beta 1 heterodimers with apparent first-order reaction kinetics after all the ATPs were converted to ADPs. In contrast, when the alpha 3 beta 3 complex reacted with Mg-ADP, the complex dissociated into dimers with apparent first-order reaction kinetics without showing the steady state of the complex. The dimers, however, re-associated into the hexamer when Mg-ATP was added. The results were well-explained by a computer simulation based on non-linear chemical dynamics, in which a reaction mechanism that incorporates the dynamic structure of the hexamer in the steady state was considered.

Adenosine Triphosphate↗
PubMed1995

Prevalence of antibodies to Borrelia spirochetes among wild small rodents in central and western Japan.

Field rodents serve as a reservoir for Lyme disease spirochetes. To evaluate the antibody responses of rodents against different Borrelia species in relation to fauna of vector ticks feeding on them, we examined 272 sera of wild rodents, Apodemus speciosus, A. argenteus, and Eothenomys smithii, obtained in 27 locations in central and western Japan from 1981 to 1994. As to prevalences by rodent species using immunoperoxidase test, A. speciosus, A. argenteus and E. smithii showed 29.4%, 11.6% and 30.8% reactivity to Borrelia japonica, 10.7%, 7.2% and 3.8% to B. afzelii, 0.6%, 1.4% and 0% to B. garinii, and 14.7%, 7.2% and 11.5% to an unknown Borrelia species designated as It type, respectively. Each antibody to B. japonica, B. afzelii and B. sp. It type was detected widely both in central and western Japan, but the antibody to B. garinii was scarcely detectable in any area and rodent species examined. Apodemus mice in high mountain altitudes tend to have antibody to B. afzelii or B. japonica, and those in lower altitudes tend to have B. japonica or B. sp. It type. All 13 Apodemus mice from which B. japonica or B. sp. It type were isolated showed higher titers of antibodies to each homologous Borrelia species. The present results indicate that these antibody prevalences among rodents may be associated with dominant Ixodes ovatus and sporadic I. persulcatus on the mainland of Japan, and that Apodemus mice may not be an efficient reservoir for B. garinii. Such a serosurvey is a useful measure to evaluate the natural distribution of the pathogen.

Animals↗
PubMed1995

Non-invasive characterization of brain tumor by in-vivo proton magnetic resonance spectroscopy.

We studied the feasibility of characterizing brain tumor tissue by localized proton magnetic resonance spectroscopy (1H-MRS). Twenty-six newly diagnosed tumors were examined by in-vivo 1H-MRS. The NAA (N-acetylaspartate)/Cho (choline) ratio of Grade 2 astrocytoma was higher than that of Grade 4. The Cho/Cr (creatine and phosphocreatine) ratio of meningioma was considerably higher than that of glioma of all grades. We have experienced only two cases of ependymoma and the Cho/Cr ratios of both were lower than that of glioma. It seems likely that 1H-MRS can be used to differentiate Grade 2 from Grade 4 in most cases of astrocytoma based on the NAA/Cho ratio, though a few cases will overlap. Meningioma can be distinguished easily from glioma, and the results of our study suggest that ependymoma shows a characteristic pattern on 1H-MRS, different from those of other brain tumors.

Aspartic Acid↗
PubMed1995

Quantitative analysis of AML1/ETO transcripts in peripheral blood stem cell harvests from patients with t(8;21) acute myelogenous leukaemia.

Peripheral blood stem cells (PBSC) have been used increasingly for haemopoietic reconstitution after marrow-ablative chemotherapy in patients with acute leukaemia because of the possibility that there is a lower risk of leukaemic contamination. We have developed a titration assay using a competitive reverse transcriptase polymerase chain reaction (RT-PCR) which is able to estimate the number of AML1/ETO transcripts so that minimal residual disease (MRD) can be monitored quantitatively in patients with t(8;21) acute myelogenous leukaemia (AML). Using a qualitative RT-PCR method, AML1/ETO transcripts could be detected in all samples from 15 first PBSC harvests and 11 second PBSC harvests obtained from 15 patients with t(8;21) AML. With our competitive RT-PCR assay, the number of AML1/ETO transcripts was found to be lower in the second PBSC harvest than that in the first in every individual. Furthermore, MRD in PBSC harvests was less than that in the corresponding bone marrow obtained on the day of PBSC collection in the individual patients studied. In 10 patients who received autologous blood stem cell transplantation (ABSCT), we could not find a relationship between the number of AML1/ETO transcripts in the infused PBSC harvests and the clinical outcome after ABSCT. The present study clearly indicates that although PBSC harvests collected after consolidation chemotherapy are contaminated by leukaemic cells, the degree of leukaemic contamination may decrease as chemotherapy is repeated. The mobilization of PBSC by repeated chemotherapy may provide an advantageous source of haemopoietic stem cells for ABSCT.

Adolescent↗
PubMed1995

Characterization of blasts from a patient with eosinophilic blast crisis of chronic myelogenous leukaemia.

We investigated the biological characteristics of 'eosinophilic' leukaemic blasts from a patient with eosinophilic blast crisis of chronic myelogenous leukaemia (CML). Southern blot analysis of the bcr gene demonstrated the identical single rearranged band in both the leukaemic blasts and mature eosinophils. IL-3, IL-5 and GM-CSF significantly enhanced proliferation and differentiation of these leukaemic blasts, and only eosinophils were generated from in vitro cultures. Those eosinophils expressed the B3A2 chimaeric messenger RNA seen in the leukaemic blasts. These observations indicate that eosinophil progenitors may be involved in the development of eosinophilic blast crisis of CML and that IL-3, IL-5 and GM-CSF act on the leukaemic eosinophil progenitors.

Blast Crisis↗
PubMed1995

Gene regulation of brain natriuretic peptide in cardiocyte hypertrophy by alpha1-adrenergic stimulation.

1. We previously demonstrated that brain natriuretic peptide (BNP) is a cardiac hormone mainly produced in the ventricle, while the major production site of atrial natriuretic peptide (ANP) is the atrium. The production and secretion of BNP and ANP in the hypertrophied ventricles were markedly augmented, serving as a compensation mechanism against ventricular overload by their natriuretic, diuretic and vasodilatory actions. 2. In the present study, we prepared an in vitro model of cardiocyte hypertrophy using cultured neonatal rat ventricular cardiocytes and alpha1-adrenergic stimulation, and examined the gene expressions of BNP and ANP during the process of cardiocyte hypertrophy. 3. The treatment of cultured ventricular cardiocytes with phenylephrine evoked cardiocyte hypertrophy around 24 h after the treatment, which was characterized by augmented expression of the myosin light chain-2 gene and increase in cell size. 4. In this model of cardiocyte hypertrophy, the steady-state level of BNP mRNA rapidly increased to the maximal level within 1 h after the treatment. In contrast, ANP mRNA began to increase at 3 h, and accumulated during the course of cardiocyte hypertrophy. The secretion of BNP from ventricular cardiocytes was also stimulated more rapidly than the ANP secretion. 5. These results indicate that the gene expression of BNP is distinctly regulated from that of ANP in cardiocyte hypertrophy, and suggest a discrete pathophysiological role of BNP as an 'emergency' cardiac hormone against ventricular overload.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1995

Numerical chromosome aberrations in bladder cancer detected by in situ hybridization.

OBJECTIVE: To investigate the relationship between interphase cytogenetics and the grade and stage of bladder cancer in patients with transitional cell carcinomas of the urinary bladder. PATIENTS AND METHODS: By use of in situ hybridization with chromosome-specific DNA probes, the copy number of pericentromeric sequences on chromosomes 7, 10, 11, 17, 18, X and Y was detected within interphase nuclei in formalin-fixed and paraffin-embedded sections of the routinely processed bladder cancers from 20 patients. The percentage of hyperdiploid cells (three or more spots) was estimated using light microscopy. RESULTS: The percentage of hyperdiploid cells for chromosomes 7, 11 and 17 was highly correlated with increasing tumour grade (P < 0.01, Spearman rank correlation) or increasing pathological stage (P < 0.01). The percentage of hyperdiploid cells for chromosome Y was not correlated with either grade or stage (P > 0.05). As high tumour grade and stage are both indicative of more aggressive tumour behaviour and a worse prognosis, these findings suggest that the percentage of hyperdiploid cells, especially for chromosomes 7, 11 and 17, may be highly predictive of bladder tumour aggressiveness. CONCLUSION: These preliminary results suggest that measurement of numerical chromosome aberrations using in situ hybridization in bladder cancer may offer a new objective and quantitative assay of the biological potential of individual tumours.

Aged↗
PubMed1995

Proliferating cell nuclear antigen cyclin in human transitional cell carcinoma.

OBJECTIVES: To confirm the value of the proliferating cell nuclear antigen (PCNA) labelling index in relation to histological grade, stage and prognosis. MATERIALS AND METHODS: Tissue specimens from 56 patients (49 men, 7 women; mean age 65 years [range 34-86]) with newly diagnosed transitional cell carcinoma of the urinary bladder were stained by an avidin-biotin peroxidase method using an anti-PCNA monoclonal antibody. Immunohistochemical analysis was performed on ethanol-fixed, paraffin-embedded tissue sections obtained by endoscopic biopsy or transurethral resection (TUR). The PCNA labelling index was determined by counting the number of PCNA-labelled cells in the tissue sections. RESULTS: Grade 1 tumours averaged 5.1 +/- 3.0% labelling versus 10.9 +/- 5.2% in grade 2 tumours, and grade 3 tumours had a PCNA labelling index of 21.8 +/- 10.4%. The average labelling indices for superficial tumour (37 patients) and invasive tumour (19 patients) were 7.5 +/- 5.3% and 20.8 +/- 10.0%, respectively. A distant metastatic bladder tumour showed an average labelling index of 42.3%. To analyse survival, tumours with PCNA indices above and below the median level (12%) were compared. Those patients with an index of < 12% (the mean of all of the PCNA values) had a worse prognosis than those with an index of > 12%. The mean PCNA labelling indices in recurrent and non-recurrent tumours were 6.4 +/- 0.7% and 8.2 +/- 1.7%, respectively, statistically not significant. CONCLUSION: The higher PCNA labelling index may indicate biological malignancy. These results suggest that measurement of the PCNA labelling index in bladder cancer may prove to be an objective and quantitative assay of biological aggressiveness and provide significant prognostic information, though it does not help to select patients at high risk of recurrence in superficial tumours.

Adult↗
PubMed1995

Developmental brain changes investigated with proton magnetic resonance spectroscopy.

Volume-selective proton magnetic resonance spectroscopy (1H-MRS) of the brain was performed with a 1.5 Tesla magnet in 47 healthy children and in six healthy adults. Peaks of N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were observed in all cases, but a lactate peak was not observed. In the right parietal region. 1H-MRS revealed increases in the rations of NAAJCho and NAA/Cr and a decrease in Cho/Cr with advancing age. The most rapid changes were noted between one and three years of age. 1H-MRS of the right frontal region also was performed in 21 cases (20 children and one adult). In the right frontal region, there was an increase in the ratio of NAA/Cho and a decrease in Cho/Cr with advancing age, while a developmental change was not observed in the ratio of NAA/Cr. The ratios of both NAA/Cho and NAA/Cr were lower in the right frontal region than in the right parietal region. These results show that developmental changes and regional variation of metabolites are observed in 1H-MRS of the brain, and need to be considered in its application.

Adolescent↗
PubMed1995

Desmosomal dissolution in Grover's disease, Hailey-Hailey's disease and Darier's disease.

Proteins involved in the formation of desmosomes and simpler adherens junctions were studied in three types of non-immune acantholytic diseases; specifically, four cases of Grover's disease (GD), one case of Hailey-Hailey's disease (HHD) and one case of Darier's disease (DD), and these were compared to two cases of immune-mediated acantholytic disease pemphigus vulgaris (PV). The proteins studied included: 1. The intracellular desmosomal proteins, desmoplakin I and II and plakoglobin; 2. The intercellular desmosomal proteins, desmoglein and CD44; and 3. vinculin, which is a major intracellular protein of the simpler aherens junctions. In GD, HHD and DD, immunostaining showed a loss of desmoplakin I and II and plakoglobin from the desmosomes, and a diffuse staining in the cytoplasm. In contrast, in pemphigus vulgaris, these proteins seemed intact and were localized to dot-like spots on the cell surface. Also, desmoglein, and CD44 were slightly affected in GD, and moderately affected in HHD and DD. Absence of desmosomal attachment plaques, the lack of labeling with desmoglein in the affected desmosomes and a diffusion of the labels into cytoplasm were demonstrated with electron microscopy using an immunogold technique. In PV, desmoglein III is one of the target antigens for the autoantibodies in this disease and was only partially preserved in a small number of lesional cells, while CD44 was mostly preserved. Vinculin was intact in GD, HHD and DD, but was lost in PV. This study, our previous work, and that of others, suggest that: 1. In GD, HHD and DD, the proteins of the desmosomal attachment plaque are primarily affected; 2. In PV, the intercellular glycoproteins are primarily involved; and 3. Simple adherens junctions are intact in GD, HHD and DD, but are damaged in PV.

Acantholysis↗
PubMed1995

Adnexal masses: accuracy of characterization with transvaginal US and precontrast and postcontrast MR imaging.

PURPOSE: To determine the accuracy of transvaginal ultrasound (TVUS) and of precontrast and contrast material-enhanced magnetic resonance (MR) imaging in the differentiation of adnexal masses. MATERIALS AND METHODS: Five blinded readers analyzed images of 80 masses in 72 patients. MR and TVUS images were interpreted in separate sessions. Findings were confirmed at surgery or laparoscopy. RESULTS: Higher diagnostic accuracy was attained with MR imaging in mature cystic teratomas and endometriomas. However, better accuracy was achieved with contrast-enhanced MR imaging and TVUS in simple cysts, cystadenomas, and malignant tumors because internal details could be visualized. Receiver operating characteristic study indicated that observer confidence was significantly higher with contrast-enhanced MR imaging than with precontrast MR imaging (P = .011) or TVUS (P = .002) in the differentiation of benign and malignant masses. CONCLUSION: Contrast-enhanced MR imaging is superior to precontrast MR and TVUS imaging in the characterization and differentiation of adnexal masses.

Adnexal Diseases↗