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Biomedical subjects

M Takamura

Publications and source records attributed to M Takamura.

At least 55 records · Page 3Linked to original sources

Treatment of aplastic anemia with antithymocyte globulin, cyclosporin A, methylprednisolone, danazol and recombinant human granulocyte-colony stimulating factor.

The main purpose of the present study was to determine the response rate to immunosuppressive therapy combined with recombinant human granulocyte-colony stimulating factor (rhG-CSF) and its efficacy for preventing infections in patients with severe aplastic anemia. The treatments included one course of antithymocyte globulin, cyclosporin A, methylprednisolone, danazole and rhG-CSF. Three patients had very severe aplastic anemia and two had moderate aplastic anemia. One patient relapsed 13 months following the first course of therapy and received a second course. Five patients received six courses of treatment and the response rate at 6 months was 83.3%. All patients achieved an absolute neutrophil count of greater than 1.0 x 10(9)/L within 40 days. All patients with a complete response are transfusion-free and doing well. All five patients are currently alive and have not had any episode of infection for 17-53 months. The results of the study indicate that this therapy may improve the poor prognosis of young patients with severe aplastic anemia. It has a good response rate and induces a rather rapid increase in the neutrophil count, which protects against life-threatening bacterial and fungal infections.

Adolescent↗

[Therapeutic effectiveness of combined microsurgery and radiosurgery in a patient with a huge trigeminal neurinoma].

A case of right trigeminal neurinoma extending from the cavernous sinus to the cerebellopontine angle in a 48-year-old male is reported. The patient first noticed right facial numbness in June 1993. Six months later, he experienced headaches with occasional nausea, diplopia, ataxic gait, tinnitus and dysphagia and was referred to our department on January 21, 1994. Neurological examination on admission showed multiple cranial nerve palsy from the 4th to 11th nerve on the right, and the cerebellar sign on the right. Initial CT and MRI revealed a large mass lesion extending from the right cavernous sinus to the right cerebellopontine angle. On February 16, 1994, radical resection of the tumor, except the lesion invading the cavernous sinus, was performed via a combined retroauricular and preauricular transpetrosal transtentorial approach. The histological diagnosis was neurinoma. The patient's postoperative course was uneventful and there was good clinical improvement, although the right facial numbness and mild diplopia persisted. On April 6, 1994, radiosurgery was performed with a maximum dose of 28 Gy and a marginal dose to 14 Gy to the remaining cavernous sinus lesion. Two weeks after radiosurgery, the patient achieved a complete return to his daily routine. Two-year follow-up CT and MRI showed a small residual les on in the right cavernous sinus alone. There was no evidence of tumor growth. No new neurological deficits had developed, and the patient's the double vision had resolved. Thus, the patient has been able to maintain a satisfactory level of activities of daily living. We wound like to emphasize the clinical value of the strategy used to treat this patient which combined microsurgery with subsequent radiosurgery.

Cranial Nerve Neoplasms↗

[Non-specific elevation of anti-dsDNA antibody measured by Farr method found in a patient with liver cirrhosis].

In a patient with liver cirrhosis, an elevation of serum anti-dsDNA antibody titer (100-193.3 IU/ml) measured by Farr method was found. This anti-dsDNA antibody was not identified by Crithidia Luciliae method, and the analysis using ELISA method showed that the DNA-antibody is an anti-ssDNA antibody (IgG) and that it is reactive only with ssDNA by the suppression test using purified DNA with lambda phage. Based on this finding, the high titer of anti-dsDNA antibody found in this patient using Farr method was considered to be non-specific cross-reaction with ssDNA.

Antibodies, Antinuclear↗

Nitric oxide induces c-fos gene expression via cyclic AMP response element binding protein (CREB) phosphorylation in rat retinal pigment epithelium.

We have examined whether nitric oxide (NO) induces the expression of c-fos proto-oncogene and the phosphorylation of cyclic AMP response element binding protein (CREB) in the rat retina. NO donor sodium nitroprusside (SNP) was injected into the vitreal cavity of the eye, and the retina and retinal pigment epithelium (RPE) was analysed by in situ hybridization using single-stranded RNA probes for c-fos transcripts and by immunocytochemistry using an anti-phospho Ser-133 antibody 20 min after the injection of SNP, phosphorylated-CREB immunoreactivity was found in RPE cells and weakly in some cells of the INL. Forty-five min after the SNP injection, the expression of c-fos mRNA was detected in the RPE. These results suggested that NO induced the c-fos expression via the phosphorylation of CREB in RPE cells, as it has been demonstrated in PC12 cells that the transcription of c-fos gene was activated by the CREB phosphorylation.

Activating Transcription Factor 2↗

Comprehensive treatment of advanced neuroblastoma involving autologous bone marrow transplant.

Encouraging results are reported with high-dose chemotherapy and total body irradiation followed by autologous bone marrow transplantation in the treatment of advanced neuroblastoma. However, relapse remains a significant problem. We used high-dose chemotherapy, surgery, intraoperative radiation and an autologous bone marrow transplant treated in vitro to remove tumor cells followed by 13-cis-retinoic acid to treat 36 children with advanced neuroblastoma. This comprehensive treatment appears to improve the survival rate of patients with advanced neuroblastoma, including those with N-myc amplification and bony involvement. The disease-free survival rate was 66% (95% confidence interval, 49-84%) at 3 years. All patients who received 13-cis-retinoic acid developed cheilitis, but no bone marrow depression occurred in these patients. Five patients developed hemolytic uremic syndrome (HUS) post-transplant. This may have been related to the procedure used for total body irradiation. Patients who had their kidneys shielded during this procedure did not develop this syndrome. Patients who received local irradiation at the primary site showed no evidence of relapse in this region, indicating that such therapy may help to prevent a relapse. These data suggest a high rate of 3 year disease-free survival with this treatment strategy. The nonrandomized nature of the study and use of multiple modalities precludes analysis of the specific contribution of each.

Adrenal Gland Neoplasms↗

Type La glycogen storage disease with focal nodular hyperplasia in siblings.

Glycogen storage disease type I (GSD-I) is an inherited disorder that is due to a glucose-6-phosphatase (G6Pase) deficiency. There have been recent reports of hepatocellular tumors in adults with this disease. Hepatic adenoma is the most common tumor described but others, including hepatocellular carcinomas, hepatoblastomas, and focal nodular hyperplasia (FNH) have been reported. FNH of the liver is a rare benign lesion that has been reported in eight patients with GSD-I. Three of these eight patients, in addition to the patient in our study, had been treated with portacaval shunts. When these patients were compared with patients who had not received such treatment, it appeared that the portacaval shunts may have induced the development of FNH and may have been associated with earlier complications. FNH is a benign tumor that may coexist with adjacent fibrolamillar carcinomas and/or adenomas and requires careful follow-up.

Child↗

Successful autologous bone marrow transplant for relapsed Ki-1 lymphoma.

We report on a 16 year old girl with relapsed Ki-1 lymphoma and a very poor prognosis. The initial manifestation was multiple bone metastases and lymphadenopathy. The patient achieved remission with modified adriamycin, bleomycin, vincristine, daunomycine therapy. However, 14 months after the completion of therapy, relapse occurred in a new cervical lymph node on the left side. After preparation with chemotherapy and total lymphoid irradiation (TLI) the patient underwent autologous bone marrow transplantation (A-BMT). Ki-1 lymphoma shows clinically diverse symptoms, but hematopoietic stem cell transplantation should be performed in relapsed cases. It may be effective to give TLI followed by A-BMT for patients such as ours who have lymph node involvement without bone marrow metastasis.

Adolescent↗

[Pharmacokinetics of intratumoral interferon-gamma activity following subcutaneous administration of recombinant interferon-gamma in a patient with metastatic brain tumor derived from renal cancer].

Pharmacokinetic studies of intratumoral interferon (IFN)-gamma activity were performed 1 week and 1 month after subcutaneous (s.c.) administration of recombinant IFN-gamma (specific activity = 1 x 10(7) units/mg protein) to a patient with metastatic brain tumor in the right occipital lobe derived from primary renal cancer. The patient, a 54-year-old man, underwent total removal of the lesion on April 10, 1991, with placement of an indwelling Ommaya Reservoir in the tumor cavity. The histological diagnosis was clear-cell carcinoma. His postoperative course was uneventful. Due to detection of a new ring-like enhancing mass in the right temporal lobe on serial CT examination on May 27, radiotherapy was discontinued immediately after delivery of a total dose of 30 Gy. Recombinant IFN-gamma was then administered s.c. at a dose of 3 x 10(6) units/day for 6 weeks, and induced a partial response. During IFN-gamma therapy, IFN-gamma activity in intratumoral fluid was measured 0 min, 30 min, 90 min and 6 hours after s.c. injection of IFN-gamma. The level of IFN activity was determined by an enzyme-linked immunosorbent assay. Intra-tumoral IFN-gamma activity gradually increased, and showed the highest of measured values at 6 hours after administration, while serum IFN activity decreased rapidly with a half-life of 30 min. The patient was discharged on July 30, but died from complications of aspiration pneumonia on September 2, 1991.

Adenocarcinoma, Clear Cell↗

A case of sellar chordoma mimicking a non-functioning pituitary adenoma with survival of more than 10 years.

A rare case of sellar chordoma occurring in a 67-year-old woman who survived for more than 10 years is presented. Clinical signs and symptoms masqueraded as a non-functioning pituitary adenoma with visual disturbance and hypopituitarism. Initial computed tomography (CT) showed an intrasellar mixed dense mass with suprasellar extension, accompanied by non-homogeneous contrast enhancement. Partial removal of the mass was accomplished via right fronto-temporal craniotomy. Histological examination revealed a typical chordoma with no malignancy. After postoperative irradiation, the patient was discharged with clinical improvement. Serial CT and magnetic resonance imaging 8 years after treatment disclosed a regrowth of the intrasellar lesion, which extended to the sphenoid sinus and clivus, accompanied by non-homogeneous contrast enhancement. The patient underwent subtotal removal of the recurrent tumor through a sublabial transsphenoidal approach. Histological examination confirmed the previous diagnosis. Immunohistochemical study demonstrated positive cytoplasmic expression of vimentin, epithelial membrane antigen, keratin and S-100 protein, in contrast with a lack of appearance of carcinoembryonic antigen. After reoperation, she completely recovered and has survived for more than 10 years with good quality of life.

Adenoma↗

[Effect of Ca(2+)-channel antagonists on the corticoidogenesis in primary cultured bovine adrenocortical cells].

We investigated the effect of Ca(2+)-channel antagonists, Nicardipine(N), Verapamil(V) and Flunarizine(F), on the corticoidogenesis(CG) in primary cultured bovine adrenocortical cells. To examine the effect on receptor operated Ca(2+)-channel(ROC) and voltage operated Ca(2+)-channel(VOC), involved in corticoid synthesis, adrenocorticotropic hormone(ACTH) and high-K+ were used respectively. With or without the antagonists, cells were incubated at 37 degrees C for 1h in the presence of ACTH (100pM) or K+ (30mM). Corticoid was measured fluorometrically using cortisol as the standard. N and V inhibited not only ACTH-induced CG, but high K(+)-induced CG in a concentration-dependent manner. However, F inhibited only high K(+)-induced CG, and did not affect ACTH-induced CG. These inhibitions were observed at the low micromolar concentrations (below 40 microM) of the antagonists. In the regulation of corticoid synthesis, we indicate that F has an inhibitory effect on VOC without ROC; on the other hand, N and V inhibit both ROC and VOC.

Adrenal Cortex↗

Procaine inhibits cyclic AMP-induced steroidogenesis in isolated bovine adrenocortical cells.

Effects of procaine on dibutyryl adenosine 3',5'-cyclic monophosphate ((Bu)2cAMP)-, Ca2(+)- or forskolin-induced steroidogenesis were examined in isolated bovine adrenocortical cells. Procaine (less than 1.0 mM) caused a marked suppression of (Bu)2cAMP- or forskolin-induced steroidogenesis in the absence of extracellular Ca2+, but did not affect on Ca2(+)-induced steroidogenesis in the cells. (Bu)2cAMP decreased the cell associated 45Ca2+. However, procaine (300 microM) inhibited this effect of (Bu)2cAMP. These results suggest that procaine may abolish (Bu)2cAMP-induced Ca2+ release from intracellular calcium store(s) and inhibits steroidogenesis.

Adrenal Cortex↗

Peripheral-type benzodiazepine receptors are involved in the regulation of cholesterol side chain cleavage in adrenocortical mitochondria.

In an attempt to elucidate the physiological relevance of the peripheral type of benzodiazepine receptor in adrenocortical mitochondria, we examined the effect of three different benzodiazepines (diazepam, Ro5-4864, and chlordiazepoxide) on the conversion of cholesterol to pregnenolone, the rate-limiting step in steroidogenesis, by using cholesterol-loaded mitochondria from bovine adrenal zona fasciculata. These benzodiazepines, except chlordiazepoxide, caused a dose-dependent stimulation of the cholesterol side chain cleavage in the mitochondria. The stimulatory effect of Ro5-4864 was approximately 10 times more potent than that of diazepam. No inhibitory effect of YM-684 (Ro15-1788), a potent antagonist to central-type benzodiazepine receptors, was observed in the stimulation induced by diazepam and Ro5-4864. Both external calcium ion and voltage-dependent calcium channel blocker, (+)-PN200-110, were without effect on the diazepam-induced steroidogenesis. By contrast, pretreatment of mitochondria with digitonin abolished the stimulatory effect of diazepam on the mitochondrial steroidogenesis. The present results indicate that the peripheral-type benzodiazepine receptor of adrenocortical mitochondria plays an essential role in regulating cholesterol side chain cleavage without any change of calcium channels.

Adrenal Cortex↗

Diazepam potentiates the corticoidogenic response of bovine adrenal fasciculata cells to dibutyryl cyclic AMP.

To provide a possible role of peripheral type benzodiazepine receptors in the regulation of glucocorticoid biosynthesis. We have examined the effect of diazepam on the corticoidogenic response to dibutyryl cyclic AMP in isolated bovine adrenal fasciculata cells. Diazepam alone (up to 100 microM) had no effect on the corticoidogenesis. Diazepam caused a dose-dependent potentiation of dibutyryl cyclic AMP-induced corticoidogenesis. However, diazepam had no effect on the corticoidogenic response to ACTH and a high concentration of KCl. The potentiating effect by diazepam was clearly detected after 90 min-incubation, and it was blocked by YM-684 (diazepam antagonist) and ML-236B (cholesterol de novo synthesis inhibitor). Diazepam caused no significant decrease of intracellular content of cholesteryl esters during the corticoidogenic response to dibutyryl cyclic AMP. When the cells were incubated in the presence of (+)-PN200-110, a potent voltage-dependent Ca channel inhibitor, the potentiating effect by diazepam was not affected in spite of a significant inhibition of dibutyryl cyclic AMP-induced corticoidogenesis. These results indicate that the potentiating effect of diazepam on dibutyryl cyclic AMP-induced corticoidogenesis is due in part to the activation of the intracellular cholesterol supply system (cholesterol de novo synthesis) without any change of voltage-dependent Ca channels.

Adrenal Cortex↗