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M Harada

Publications and source records attributed to M Harada.

At least 757 records · Page 42Linked to original sources
PubMed1993

[Study on the inhibitory effect of oral granisetron against nausea/vomiting induced by cytosine arabinoside containing chemotherapy for tumors in the hematopoietic organs].

We investigated the antiemetic effect, safety and usefulness of granisetron tablet on nausea/vomiting induced by cytosine arabinoside (Ara-C) in the chemotherapy for tumors in the hematopoietic organs. Out of 52 cases with malignant tumors in the hematopoietic organs including acute leukemia, 30 in granisetron group had no antiemetic treatment, were evaluated for the clinical efficacy of granisetron and 22 in control group. Their chemotherapies were combination therapy with Ara-C and daunorubicin (DNR), Ara-C and mitoxantrone (MIT), or Ara-C and etoposide (VP-16). In the trial, the dosage of granisetron tablet was 2 mg once a day, and the drug was given before each chemotherapy for 6 consecutive days. In clinical efficacy the effective rate of granisetron (the percentage of cases in which the trial drug was assessed as "Remarkably effective" or "Effective") was more than 80% on each day of administration. There was no adverse event. As the abnormal laboratory test value, only 1 case tested positive in urine protein, whose causal relation to the trial drug was judged as "Unassessable". Granisetron was judged as "Safe" in 31 out of 32 cases (96.9%). In terms of usefulness, the drug was rated "Extremely useful" or "Useful" in 26 out of 30 cases (86.7%). The above results have shown that granisetron tablet, when administered orally once daily at a dose of 2 mg, has an excellent antiemetic effect, and is a safe and useful drug.

Administration, Oral↗
PubMed1993

Biliary copper excretion in acutely and chronically copper-loaded rats.

Biliary copper excretion was examined in rats with acute, continuous and chronic copper loads. Copper was excreted into bile, and the concentration peaked 40 min after a venous injection of copper sulfate (127 ng/gm body weight). The excretion was significantly inhibited by colchicine. Therefore some copper may be transported in hepatocytes by a vesicular pathway and excreted into bile. Biliary copper output increased over time and reached a plateau 180 min after a continuous venous infusion of copper sulfate (318 ng/gm body weight/hr) had started, when the concentration of copper in bile was much higher than that in plasma; the bile/plasma ratio of copper concentrations was 4.32 +/- 0.46. These data support the idea that copper transport involves a specific uptake and transport system. In chronically copper-loaded rats, hepatic copper content was significantly increased compared with controls, and reaction products for copper were observed in hepatocyte granules by light microscopic examination with p-dimethylaminobenzylidene rhodanine stain. The number of lysosomes in hepatocytes increased and the shape changed. In chronically copper-loaded rats the number of tubular lysosomes was very high. However, other organelles appeared to be normal. In these rats biliary excretion of not only copper but also acid phosphatase, a lysosomal enzyme, was significantly greater than the control. Therefore hepatocyte lysosomes may play an important role in biliary copper excretion. Furthermore, when biliary lysosomal excretion increases, the tubular lysosomes actively participate in this excretion.

Acid Phosphatase↗
PubMed1993

Selective removal of beta 2-microglobulin from plasma specimens of long-term hemodialysis patients by high-performance immunoaffinity chromatography.

We examined the suitability of high-performance immunoaffinity chromatography (HPIAC) for removing beta 2-microglobulin (beta 2-MG) from plasma of patients (n = 26) undergoing long-term hemodialysis. We used immobilized antibody to beta 2-MG to prepare an immunoaffinity column with a 0.5-mL bed volume. Plasma samples of 0.5 mL were chromatographed at a flow rate of 0.5 mL/min and pressures < 7 kg/cm2. Although only a small amount of beta 2-MG can be removed with a conventional dialyzer, 92.1% +/- 0.4% of the globulin could be removed by HPIAC. The column could be reused after acid elution. After 50 cycles the efficiency of beta 2-MG trapping was 73% of the original efficiency.

Adult↗
PubMed1993

[Subrenal capsule assay of nude mice for testing the effectiveness of UFT for rat prostatic carcinoma (R3327)].

Combination effect of UFT and CDDP against the rat prostatic carcinoma (R3327) was evaluated by the subrenal capsule assay in nude mice. The tumor growth of R3327 was inhibited in proportion to the UFT concentration. Anticancer effect of UFT was elevated by co-administration of CDDP. These data suggest a clinical usefulness of UFT administration with CDDP for hormonally refractory advanced prostatic carcinoma.

Animals↗
PubMed1993

[The growth activity and DNA ploidy in anaplastic carcinoma transplanted to nude mice].

Recently, nuclear DNA contents of various human tumors were studied, and DNA aneuploidy was thought to have prognostic significance in many kinds of malignant tumors. Although the same significance was reported in thyroid carcinoma, the anaplastic thyroid carcinoma which is one of the most aggressive tumor in human malignant neoplasms, not always shows DNA aneuploidy. Therefore, using 3 xenografts established from 3 patients with anaplastic thyroid carcinomas, we investigated their growth activity, DNA ploidy and chromosome abnormalities. Two of these xenografts grew relatively fast in nude mice showing diploid or near diploid state in a flow cytometric study, and also, showed many structural abnormalities in chromosome analysis by the G-banding technique. The remaining one xenograft showed slower growth and aneuploidy, and had extensive numerical but less structural variability in its chromosomal constitution. These results indicate that some tumors showed DNA diploidy and have structural chromosome abnormalities and also suggest that the prognostic value of quantitative DNA measurement is limited in such tumors.

Aneuploidy↗
PubMed1993

[Idiopathic interstitial pneumonitis possibly associated with chronic graft-versus-host disease].

We described two cases of idiopathic interstitial pneumonitis (IP) after allogeneic bone marrow transplantation (BMT), who were successfully treated with prednisolone (PSL). A 40-year-old male with AML (M3) in the first remission (case 1) and a 36-year-old male with CML in chronic phase (case 2) were treated with BMT from HLA genotypically identical female siblings. Both patients were conditioned with busulfan (16mg/kg) and cyclophosphamide (120mg/kg), and given a combination of cyclosporin A and methotrexate to prevent acute GVHD (aGVHD). Engraftment of donor marrow was documented in both cases. Grade I of aGVHE developed in case 1 and no aGVHD in case 2. Both patients had clinical manifestations of chronic GVHD (cGVHD), which were followed by dyspnea and cough without fever 120 days (case 1) or 100 days (case 2) after BMT. Abnormal lung function tests and radiographic infiltrates indicated that patients developed IP, but causative microorganisms could not be detected in the bronchoalveolar lavage (BAL) specimens. Subjective symptoms disappeared in a few days after administering PSL (1mg/kg/day). Laboratory data also improved thereafter. These observations, including the development of radiographic infiltrates along with clinical manifestations of cGVHD, absence of febrile episodes, absence of causative microorganisms in the BAL specimens, and effectiveness of immunosuppressive drugs, suggested that idiopathic IP observed in our cases might be a manifestation of cGVHD.

Adult↗
PubMed1993

[Effectiveness of a community-based education program on blood pressure reduction for cardiovascular disease prevention].

To evaluate the effectiveness of lifestyle modification community-based programs on blood pressure reduction, blood pressure changes were examined according to frequency of attendance at these adult classes. The subjects were 1,017 men and women aged 40-69 who participated in a survey from 1985 to 1987, whose blood pressure was > = 140 mmHg for systolic, and/or > = 90 mmHg for diastolic and/or with antihypertensive medication use in the earlier 1981-1984 surveys. Adult classes were conducted eleven times between 1982 and 1987, emphasizing primarily reduction of salt intake, weight control if necessary, and alcohol modification. Blood pressure changes between 1981-1984 and 1985-1988 were examined in relation to the number of classes attended, stratified by antihypertensive medication use. In the group with no medication use in both surveys (n = 347), there was a significantly larger decline in systolic and diastolic blood pressures with an increase in the number of classes attended (p < 0.001). A similar trend was observed in other groups: a starting medication group (n = 198), a quitting medication group (n = 100) and a continuous medication group (n = 372). The blood pressure trend in the no medication group remained significant after controlling for age, initial blood pressure, follow-up years and the number of follow-up screenings attended. For the no medication group, there was no significant association between the number of classes attended and changes in relative weight index and alcohol intake. The proportion of persons reporting dietary modification of reduction in salt was larger, and mean 24-hour urine sodium excretion was smaller, with increasing number of classes attended in the 1985-1988 surveys. Furthermore, the proportion of persons who were able to reduce salt intake between the two survey periods was higher with an increase in the number of classes attended. Mean urine sodium excretion was smaller in those who reported reduction of salt intake than those who did not. Although this study is not a randomized controlled trial, these results suggest that a community-based education program of adult classes can be effective in reduction of blood pressure levels through modification of diet.

Adult↗
PubMed1992

The alpha 3 beta 3 and alpha 1 beta 1 complexes of ATP synthase.

Two catalytic structures of H(+)-motive ATP synthase (Fig. 1), the alpha 3 beta 3 oligomer (M(r) = 319,581) and alpha 1 beta 1 promoter (M(r) = 106,527) (Fig. 2), were isolated using high pressure liquid chromatography (Fig. 3) and polyacrylamide gel electrophoresis (Figs. 4 and 5). These were reconstituted from the alpha and beta subunits of thermophilic F1 (TF1), and the alpha 3 beta 3 oligomer was also crystallized. Common to both F1 and the alpha 3 beta 3 oligomer were the nucleotide specificity, the two Km values, the presence of protomer-oligomer activities, and the one-hit--one-kill phenomenon. A synchrotron experiment on the ATP hydrolysis cycle revealed the dynamic shrinkage and expansion of F1(44) that correspond, respectively, to the ATP-induced association and ADP-induced dissociation of the alpha 3 beta 3 oligomer. The oligomer, like mitochondrial F1 and TF1, exhibited two kinds of ATPase activity: one was cooperative and was inhibited by only one inhibitor per hexamer, and the other was inhibited by three inhibitors per hexamer.

Adenosine Triphosphate↗
PubMed1992

[A case of panhypopituitarism with normal height manifesting the transection of the pituitary stalk and the formation of the ectopic and eutopic posterior lobes].

A 33-year-old man with hypopituitarism is documented. He was born at breech presentation without asphyxia. He was the shortest in his class throughout his school days. He kept slowly growing and reached 172.8 cm at the age of 33. He was devoid of secondary sexual characteristics. Endocrinological studies showed panhypopituitarism with elevated levels of plasma TSH (15.0 microU/ml). TRH administration resulted in a marked increase in plasma TSH. Posterior pituitary function was normal. MR imaging showed transection of the pituitary stalk and the presence of ectopic and eutopic posterior lobes. The replacement of corticosteroid was initiated, and exaggerated response of TSH to TRH disappeared. Delayed bone maturation due to hypogonadism and hypothyroidism was one of the reasons why he had normal height without GH therapy. The significance of his peculiar MRI findings remains to be determined.

Adult↗
PubMed1992

Prognostic significance of the expression of ras oncogene product in non-small cell lung cancer.

The clinical significance of ras oncogene expression in non-small cell lung cancer was evaluated in 116 surgically treated patients. Archival paraffin sections of the tumors were analyzed immunohistochemically using anti-ras p21 monoclonal antibody (MoAb) rp-35, and p21 staining was correlated with clinicopathologic parameters and survival. Positive reactions (+ and ++) were observed in 72.5% of the adenocarcinomas and 55.6% of the squamous cell carcinomas studied. The T1 tumors showed a ++ reaction less frequently than T2 and T3 tumors (P less than 0.05). Stage I tumors also were less reactive with MoAb rp-35 than tumors in more advanced stages (P less than 0.05). Survival analysis showed that patients with p21-negative tumors had significantly longer survival times (a 5-year survival rate of 64.1%) than those with p21 + tumors (38.0%, P less than 0.05) or those with p21 ++ tumors (11.5%, P less than 0.005). The significant correlation between p21 staining and patient survival was independent of histologic type, stage of disease, tumor or node status, and the resectability of tumors. On Cox's multivariate analysis, p21 staining was a major and independent prognostic determinant of survival. These results suggest that enhanced ras p21 expression may be one of the important biologic and clinical markers indicating the malignant potential of non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed1992

Analysis of the roles of CD4+ and CD8+ T cells in autoimmune diabetes of NOD mice using transfer to NOD athymic nude mice.

The NOD mouse, which spontaneously develops insulitis and overt diabetes, is a model of autoimmune type I diabetes mellitus. For the precise analysis of the roles of CD4+ and CD8+ T cells in the pathogenesis of this mouse, these subsets must be transferred into recipients that are completely free of T cells and pathological changes. We used athymic NOD nude mice, which congenitally lack mature T cells and are free of insulitis and hyperglycemia up to the age of 60 weeks, as recipients for this purpose. To the nude recipients we transferred either one of a highly purified CD4+ or CD8+ T cell subset derived from non-diabetic female NOD mice; any in vivo increase in the contaminating T cell subsets was prevented by injecting the antibody homologous to it. Most of the T cell-reconstituted recipients were treated with cyclophosphamide to promote the onset of overt diabetes. Transfer of the CD8+ T cell subset alone did not induce insulitis or hyperglycemia. In contrast, transfer of the CD4+ T cell subset alone produced insulitis, but not hyperglycemia, in all the recipients. However, the subsequent transfer of CD8+ T cells into CD4+ T cell-reconstituted recipients induced severe insulitis and hyperglycemia in almost all the recipients. In these diabetic recipients, we observed severe damage of the pancreatic islets and the infiltration of a large number of CD8+ T cells into the remaining islets; insulin-secreting beta cells were no longer detected. These results suggest that CD4+ T cells play a predominant role in the development of insulitis and that CD8+ T cells migrate into the islets and are subsequently, with the aid of CD4+ T cells, differentiated into killer cells which act against beta cells.

Animals↗
PubMed1992

Folinic acid does not mobilize hemopoietic progenitors following repeated consolidation chemotherapy for acute leukemia.

Folinic acid (FA) has been reported to expand the pool of peripheral blood stem cells (PBSC) after chemotherapy. We evaluated the efficacy of FA for harvesting PBSC following cytotoxic chemotherapy in 4 patients with acute leukemia. After achieving a complete remission (CR), 3 courses of chemotherapy for a consolidation of the CR were administered to the patients. Two successive cycles of leukapheresis were performed during the recovery phase from consolidation chemotherapy, which consisted of an intermediate dose of cytosine arabinoside. For the second cycle of leukapheresis, FA was administered intravenously at a dose of 50 mg/day following consolidation. The yields of either mononuclear cells or burst-forming units-erythroid (BFU-E) were not affected by FA administration. In contrast, the yields of colony-forming units-granulocyte/macrophage (CFU-GM) were significantly decreased in all patients compared to the CFU-GM yields after the first cycle of leukapheresis (P = 0.032). Thus FA is considered not to be effective in expanding the peripheral blood progenitor pool when given in a fashion different from the original report.

Acute Disease↗
PubMed1992

Analysis of bone metastasis of prostatic adenocarcinoma in 137 autopsy cases.

Metastatic frequency to various organ sites in 137 autopsy cases with histologically confirmed prostatic adenocarcinoma was examined retrospectively. Bone lymph node metastases were observed in 81% and 82.5% of the cases, respectively. Lung and liver metastases were noted in 46.7% and 30.7% of the cases respectively. Statistical analysis of the inter-relation among metastases to the bones, lymph nodes, lungs and liver revealed that 83.2% of cases with lymph node metastasis also had bone metastasis. Sixty out of 64 cases with lung metastasis also presented with bone metastasis. There was a significant correlation of metastases between bones and lymph nodes, bones and lungs, and lymph nodes and lungs. Although approximately 88% of cases with liver metastasis also had bone metastasis, this relationship was not statistically significant. there was a statistically significant relationship between lung metastasis and specific sites of bone metastases, i.e. vertebrae, ribs, and sternum. Using the Cochran-Mantel-Haenszel statistical method, we found that the metastatic combination between lung and bone was significantly related in cases with or without lymph node metastasis. These observations suggest that the Batson's vertebral system might play an important role in the metastatic spread of prostatic adenocarcinoma either to the bones or lungs.

Adenocarcinoma↗
PubMed1992

Clinical study of bone-related relapse in prostate carcinoma.

Prostate carcinoma is usually highly responsive to initial endocrine therapy. However, when relapse occurs, the subsequent clinical course is very poor. In this study, we tried to reveal the clinical aspects of bone-related relapse in 392 patients who received endocrine therapy for prostate carcinoma. In 17 stage B patients who had relapsed, 76% experienced relapse within 4 years following the start of treatment, 76% within 3 years in 27 stage C patients, and 71% within 2.5 years found in 45 stage D patients. Pre-treatment levels of serum enzymes and initial response of the primary lesion and of serum enzymes failed to predict relapse. The Gleason sum tended to be correlated with relapse. In particular, patients with a Gleason sum of 9-10 had a lower non-relapse rate during the follow-up period than patients with lower sums. With the recent use of more sophisticated measurements of PSA and/or PAP, the reduction rate or interval to normalization of the markers must be more relevant to predicting relapse.

Acid Phosphatase↗
PubMed1992

Role of the vertebral venous system in metastatic spread of cancer cells to the bone.

Bromodeoxyuridine (BrdU) labeled human prostatic cancer cells, PC-3, and murine osteosarcoma cells, POS-1 were injected into the tail veins of male mice under concomitant temporal occlusion of inferior vena cava. Five minutes after release of the venous occlusion, animals were sacrificed and various tissues, organs and the vertebral bones were examined immunohistochemically using an application of BrdU-anti-BrdU methods. Obvious BrdU labeled tumor cells, isolated or clumped, were demonstrated within the venous channels along the vertebral column, the epidural venous channels around spinal nervous tissues, in the bone marrow of lumbo-sacral vertebrae and intra- and peri-prostatic venous channels. The results suggest that a blockade of short duration of venous flow at the inferior vena cava can result in the bypassing of tumor cells through the vena cava to the vertebral venous system, which has a close connection with the peri-prostatic venous plexus. Thus, the vertebral venous system may play an important role in the metastasis of prostatic carcinoma to bone. In addition this experimental procedure is a very valuable model for studying mechanisms and prevention of bone metastases from prostatic carcinoma.

Adenocarcinoma↗
PubMed1992

Calcium regulating activity of 26,27-dialkyl analogs of 1 alpha,25-dihydroxyvitamin D3.

A series of analogs of 1 alpha,25-dihydroxyvitamin D3[1,25(OH)2D3] with alkyl substitutions in 26- and 27-positions were tested for calcium (Ca) regulating activity. The potencies of dialkyl analogs in stimulating bone resorption in neonatal mouse calvaria cultures were the highest in 1 alpha,25-dihydroxy-26,27-dimethylvitamin D3[1,25(OH)2-(Me)2D3], followed by 1,25(OH)2D3, 1 alpha,25-dihydroxy-26,27-diethylvitamin D3[1,25(OH)2(Et)2D3], and 1 alpha,25-dihydroxy-26,27-dipropylvitamin D3[1,25(OH)2(Pr)2D3] in that order. A similar order of potential regarding formation of osteoclast-like cells in mouse bone marrow cell cultures and on bone Ca mobilization with long-term vitamin D-deficient rats was observed in the same series. The relative potencies of 1,25(OH)2D3, 1,25(OH)2(Me)2D3, 1,25(OH)2(Et)2D3, and 1,25(OH)2(Pr)2D3 in competing with 1,25(OH)2D3 for binding to chick intestinal cytosol receptors were 1:1:0.16:0.036. A similar order of potential in case of intestinal Ca transport in situ was observed in the same series. The potencies of dialkyl analogs in competing with 25-hydroxy-vitamin D3 for binding to rat serum vitamin D binding protein were much lower than that of 1,25(OH)2D3. Effect of 1,25(OH)2(Me)2D3 on osteopenia in rats induced by ovariectomy and right sciatic neurotomy was higher than that of 1,25(OH)2D3. From these results, the lengthening by one carbon at 26- and 27-positions was shown to maintain the Ca regulatory activity of 1,25(OH)2D3.

Animals↗