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M Morimoto

Publications and source records attributed to M Morimoto.

At least 19 recordsLinked to original sources
PubMed1992

c-kit Gene was not transcribed in cultured mast cells of mast cell-deficient Wsh/Wsh mice that have a normal number of erythrocytes and a normal c-kit coding region.

The Wsh is a mutant allele at the W (c-kit) locus of mice. Mice of Wsh/Wsh genotype have white hairs and black eyes. Although adult C57BL/6-Wsh/Wsh mice were not anemic, they showed a remarkable depletion of mast cells. Most homozygous or double heterozygous mutant mice at the W (c-kit) locus, of which mast-cell depletion was comparable to that of Wsh/Wsh mice, are deficient in germ cells. However, male and female Wsh/Wsh mice have an appreciable number of germ cells in their gonads. We investigated the mechanism of specific depletion of mast cells in Wsh/Wsh mice. Cultured mast cells (CMC) derived from the spleen of Wsh/Wsh mice neither attached to normal (+/+) fibroblasts nor survived in the coculture with +/+ fibroblasts. The c-kit messenger RNA (mRNA) was strongly expressed in +/+ CMC, but not detectable in Wsh/Wsh CMC. Despite the lack of c-kit mRNA in Wsh/Wsh CMC, the c-kit mRNA was normally detectable in the cerebellum and weakly detectable in the testis and spleen of Wsh/Wsh mice. No significant changes were found in the nucleotide sequence of the c-kit transcripts obtained from the cerebellum of Wsh/Wsh mice. Development of mast cells, erythrocytes, and germ cells in Wsh/Wsh mice appeared to be parallel with the magnitude of the c-kit gene expression in each cell type.

Anemia↗
PubMed1992

New potent mitomycin derivatives: synthesis and antitumor activity of 7,7-(ethylenedioxy)mitomycins.

A series of 6,7-dihydro-7,7-(ethylenedioxy)mitomycins was synthesized and evaluated for antitumor and anticellular activities. These compounds were prepared by basic treatment of 7-methoxymitomycins with ethylene glycol, and were structurally novel mitomycin derivatives containing a masked quinone moiety. 5,6-Enol or 6-chloro derivatives of 6,7-dihydro-7,7-(ethylenedioxy)mitomycins were also prepared and the (allyloxy)carbonyl group at the aziridine nitrogen has proved to be an efficient protecting group in chemical modification of mitomycins. Most of these mitomycin derivatives displayed potent antitumor activity against P388 leukemia in mice and anticellular activity against HeLa S3 cells.

Animals↗
PubMed1992

Antitumor quinolones with mammalian topoisomerase II mediated DNA cleavage activity.

Ninety quinolones were evaluated to determine whether their ability to induce mammalian topoisomerase II mediated DNA cleavage in vitro correlated with their antitumor activity in vivo. Ten quinolones generated linear DNA at a yield of more than 10% of substrate supercoiled DNA in the mammalian topoisomerase II mediated DNA cleavage assay. All of these compounds showed a significant increase in life span (greater than 20%) in the murine leukemia P388 model. These antitumor quinolones have closely related structures: two halogens at C-6 and C-8; and cyclopropyl at N-1 of quinolone skeleton. In contrast, many analogues of the above quinolones, as well as new quinolones used clinically as an antibacterial drug, did not induce the cleavable complex in vitro or show antitumor activity in vivo. These findings indicate that quinolone derivatives can be a promising new class of antitumor agent targeting mammalian topoisomerase II.

Animals↗
PubMed1992

Antitumor effect of KT6124, a novel derivative of protein kinase inhibitor K-252a, and its mechanism of action.

Novel derivatives of K-252a, (8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl- 8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibe nzo[a,g]-cycloocta[cde]trinden-1-one, an inhibitor of protein kinases and calmodulin-dependent phosphodiesterase, were synthesized and evaluated for their antitumor activity in vitro and in vivo. Of ten derivatives tested, four were active against the P388 murine leukemia i.p.-i.p. system, although K-252a was inactive. Among these derivatives, KT6124 was selected for further biological evaluation studies because its efficacy was the highest. KT6124 was also active against sarcoma 180 and B16 melanoma. It exerted a relatively broad spectrum of antiproliferative activity against 20 human tumor cell lines in vitro. To determine the mechanism(s) of action underlying the antitumor activity of KT6124, we tested the drug for inhibition of protein kinases, including Ca(2+)- and phospholipid-dependent protein kinase (PKC), in intact A431 human epidermoid carcinoma cells in comparison with the PKC-inhibitory activity of K-252a. KT6124 did not antagonize the action of phorbol 12-myristate 13-acetate (PMA) in A431 cells, whereas K-252a did, suggesting that KT6124 may not act on protein kinases in the cells. The interaction of KT6124 with DNA in living cells was examined by the alkaline elution method. KT6124 apparently exhibited DNA scission both dose- and time-dependently in the target cells. The DNA breakage was dependent on proteinase K treatment, suggesting its possible interaction with DNA-related enzyme(s). These results indicate that KT6124 exerts antitumor activity by acting on DNA or on DNA-related enzyme(s) in tumor cells rather than via the inhibition of protein kinases.

Animals↗
PubMed1992

In vivo and in vitro antitumor activity of mitomycin C conjugates at 7-N position through a linker containing thiocarbamate bond with CD10 monoclonal antibody.

Through a linker containing thiocarbomate bound to the 7-N position of mitomycin C (MMC), conjugates with a monoclonal antibody to CD10 (NL-1) were prepared, and their antitumor activities were examined. All five conjugates, except one, showed in vitro cytotoxicity to two CD10+ lymphoid cell lines superior to MMC. The conjugate displaying the highest cytotoxicity was selected and further tested against three CD10+ and two CD10- lymphoid cell lines in vitro. The conjugate with NL-1 antibody demonstrated higher cytotoxic activity against CD10+ tumor cells than the control conjugate with normal immunoglobulin, while there was no significant difference, when tested against CD10- tumors. The cytotoxic activity of the NL-1 conjugate to CD10+ tumors was significantly blocked by NL-1 antibody. In vivo antitumor activity of the NL-1 conjugate was then tested against a CD10+ tumor transplanted to nude mice, and side effects were recorded. The NL-1 conjugate (4 mg/kg) showed an in vivo antitumor effect similar to MMC (2 mg/kg), which is at nearly maximal tolerable dose; the latter induced decreases in numbers of leukocytes and platelets, while the former did not, suggesting less side effect by the NL-1 conjugate. Since MMC demonstrates a broad spectrum of antitumor activity, the conjugate, as such, may be applicable for the treatment of cancer patients.

Animals↗
PubMed1992

Adjuvant radiotherapy after complete resection of thymoma.

Seventy patients were studied after undergoing complete resection of thymoma to determine the effect of postoperative adjuvant mediastinal radiotherapy on prognosis, with regard to clinical stage, histological type, and pleural factor. Pleural factor was defined as follows: p0, no adhesion to the mediastinal pleura; p1, fibrous adhesion to the mediastinal pleura without microscopic invasion; and p2, microscopic invasion of the mediastinal pleura. Recurrence of thymoma after complete resection was observed in 13 patients, 12 (92%) with pleural dissemination, 6 (46%) with local recurrence, and 2 (15%) with distant metastasis (types of recurrence are overlapping). In stage I and stage II p0 patients, no recurrence was observed, regardless of mediastinal radiotherapy. Whereas mediastinal irradiation completely prevented recurrence in stage II p1 patients, 4 (36.4%) nonirradiated stage II p1 patients experienced recurrence. In stage II p2 patients, 75% had pleural dissemination even after radiotherapy. A high incidence of recurrence was also observed in stage III, nonirradiated (25%) and irradiated (30%) patients. The results suggest that mediastinal irradiation for stage I and II p0 patients is not always necessary, and that therapy for stage II p1 is essential and also expected to decrease the recurrence rate. On the other hand, in stage II p2 and stage III thymomas, mediastinal irradiation is not sufficient to prevent pleural recurrence even after complete resection. Our classification based on pleural factor is useful for better selection of appropriate postoperative treatment for thymoma patients.

Adolescent↗
PubMed1992

Thin-rim enhancement in Gd-DTPA-enhanced magnetic resonance images of tuberculoma: a new finding of potential differential diagnostic importance.

The article describes rim enhancement seen on Gd-DTPA-enhanced magnetic resonance (MR) images of two patients with tuberculoma. Pathologic examination of the surgical specimens disclosed that the peripheral portion of the tuberculoma, which showed contrast enhancement, was composed mainly of a fibrous capsule and epithelioid granulomas and that the central zone, which showed no contrast enhancement, was composed of caseous necrotic material. In a retrospective study of MR images from 20 consecutive cases of surgically proven bronchogenic carcinoma, none showed a thin enhancing rim on postcontrast MR images. Although confirmation of these findings must await further experience, the postcontrast MR findings described here may prove to be of value in distinguishing tuberculoma and possibly other granulomatous lesions from bronchogenic carcinoma.

Adult↗
PubMed1992

Functional heterogeneity of rat liver macrophages: interleukin-1 secretion and Ia antigen expression in contrast with phagocytic activity.

To clarify whether immunological heterogeneity exists among liver macrophages and whether this possible heterogeneity corresponds to varying degrees of phagocytic activity, we fractionated liver macrophages according to size via centrifugal elutriation and studied their ability to ingest latex beads, to express Ia antigen and to secrete interleukin-1 (IL-1) in vitro. Larger liver macrophages were found to be more active in ingesting latex beads than smaller ones (p less than 0.01), while smaller liver macrophages were more active in Ia antigen expression and evidenced greater fluorescence at cytofluorometric examination. In addition, smaller liver macrophages elaborated more IL-1 than the larger liver macrophages (p less than 0.05). These results indicate that liver macrophage heterogeneity is seen in at least two important macrophage functions: phagocytosis of large molecules, which provides an important scavenger function, and Ia antigen expression and IL-1 secretion, important components of the immune response.

Animals↗
PubMed1992

A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto).

We have identified a 65-yr-old nonobese Japanese man with diabetes mellitus, fasting hyperinsulinemia (150-300 pM), and a reduced fasting C-peptide/insulin molar ratio of 2.5-3.0. Fasting hyperinsulinemia was also found in his son and daughter. Analysis of insulin isolated from the serum of the proband and his son by reverse-phase high performance liquid chromatography revealed a minor peak coeluting with human insulin and a major peak of proinsulin-like materials. The insulin gene of the patient was amplified by the polymerase chain reaction and the products were sequenced. A novel point mutation was identified in which guanine was replaced by thymine. The substitution gives rise to a new HindIII recognition site and results in the amino acid replacement of leucine for arginine at position 65. These results indicate that the amino-acid replacement prevents recognition of the C-peptide-A chain dibasic protease and results in an elevation of proinsulin-like materials in the circulation. Furthermore, in this family the proinsulin-like materials is due to a biosynthetic defect, inherited as an autosomal dominant trait. Rapid detection of this mutation can be accomplished by HindIII restriction enzyme mapping of polymerase chain reaction-generated DNA, which enables us to facilitate the diagnosis and screening.

Adult↗
PubMed1992

MR imaging of thymoma: radiologic-pathologic correlation.

MR images in 17 patients with surgically proved thymomas (12 malignant and five benign) were reviewed and compared with pathologic specimens. In nine cases, MR images of excised specimens also were made and evaluated. On T2-weighted images, 11 of 12 malignant thymomas had an inhomogeneous signal intensity, half with and half without a lobulated internal architecture. None of the five benign thymomas had a lobulated internal architecture, and they all had a moderately or slightly inhomogeneous signal. Cystic regions and/or hemorrhage were noted pathologically, and corresponded to areas of inhomogeneous high signal intensity seen on T2-weighted images. Examination of the excised specimens in malignant thymomas showed that the lobulated configuration seen in the tumors was caused by thick fibrous septa. Our experience suggests that, although calcification cannot be identified, MR is helpful in making a differential diagnosis of mediastinal tumors and in determining malignancy of thymoma.

Adult↗
PubMed1992

Intrathoracic neurogenic tumors: MR-pathologic correlation.

An MR-pathologic correlation of nine intrathoracic neurogenic tumors (three neurofibromas, four schwannomas, and two ganglioneuromas) was performed to characterize their MR appearances. The three types of intrathoracic neurogenic tumor were found to have characteristic appearances on MR images that should be helpful when establishing the differential diagnosis of posterior mediastinal tumors. The MR and histologic features of these tumors are illustrated and described in this essay.

Adolescent↗
PubMed1992

[The clinical effect of intravenous regional sympathectomy with guanethidine in the management of sympathetically maintained pain].

We treated 25 patients suffering from sympathetically maintained pain with intravenous regional sympathectomy with guanethidine. Of these patients, 18 had reflex sympathetic dystrophy; 5 had causalgia; and 2 had shoulder hand syndrome. The visual analog scale before IRS therapy was 6.1 +/- 0.3, and after therapy, it was 2.3 +/- 0.4. The mean rate of improvement was 54.2% in reflex sympathetic dystrophy and 81.0% in causalgia. The therapy was particularly effective in patients with shoulder hand syndrome. These results suggest that intravenous regional sympathectomy with guanethidine could be effective for sympathetically maintained pain.

Adult↗
PubMed1992

[Results of patients in stage I and II primary lung cancer with curative resection].

We analyzed 91 patients who had curative resection from 1982 to 1989 for stage I and II primary lung cancer. The 5-year survival rates were 71.4% for stage I and 44.7% for stage II. The 5-year survival rates were 86.6% for T 1 N 0 M 0, 47.3% for T 2 N 0 M 0, 56.3% for T 1 N 1 M 0, and 37.9% for T 2 N 1 M 0. There was no cancer death in patients with squamous cell carcinoma of T 1 N 0 M 0. For stage I, tumor diameter was significant factor to influence survival. Although there was a statistically significant difference between stage I and II in patients with adenocarcinoma, there was no significant difference in those with squamous cell carcinoma. Chemotherapy had no significant improvement in survival for stage I and II lung cancer.

Adenocarcinoma↗
PubMed1992

[A case of aortic valve stenosis and regurgitation with idiopathic thrombocytopenic purpura].

A patient of aortic valvular disease with idiopathic thrombocytopenic purpura underwent aortic valvular replacement. We report a preventive measure against the intra and postoperative bleeding. The patient was a 67-year-old man. He was diagnosed as aortic valvular stenosis with regurgitation. There was no abnormal data about the coagulation test. Thrombocyte count was 8.2 x 10(4)/mm3, but thrombocytopenic life span had shortened 3.8 days. So, we used gamma-globulin 400 mg/kg/day for 5 days before the day of operation and infused blood platelets on the day of operation. There was no problem intra and postoperative period. On the 14th postoperative day thrombocyte count increased to 22.9 x 10(4)/mm3, and thrombocytopenic life span returned to normal range (7.6 days). But on the 45th day of postoperation, thrombocyte count decreased to 11.0 x 10(4)/mm3. We think that many gamma-globulin medication is a useful method to prevent intra and postoperative bleeding resulting from idiopathic thrombocytopenic purpura.

Aged↗
PubMed1992

Elevated interleukin-6 and gamma-globulin during interferon therapy of hepatitis B.

A 49-yr-old man with chronic hepatitis B manifested hypergammaglobulinemia, lymphadenopathy, and a high serum interleukin-6 level following treatment with recombinant human alpha-interferon. One month later, when the patient was treated with natural beta-interferon, serum levels of interleukin-6 and gamma-globulin increased again. The serum gamma-globulin decreased to the pretreatment level after discontinuation of interferon therapy. The serum alanine aminotransferase level remained normal for 6 months. In this case, hypergammaglobulinemia and lymphadenopathy, as well as the elevated serum interleukin-6 level, were considered to be signs of highly enhanced humoral immunity related to alpha- and beta-interferon therapy.

Alanine Transaminase↗
PubMed1992

[A case of malignant localized visceral pleural mesothelioma].

We experienced malignant localized mesothelioma of which origin was visceral pleura. According to, 1) the preoperative chest X-ray and chest CT which showed extra-pleural sign, 2) the rapid tumor growth, and 3) the result from needle biopsy, we diagnosed malignant localized mesothelioma of which origin was parietal pleura. Surgical treatment was performed, and diagnosed that its origin was visceral pleura. The tumor invaded the lung. It is dangerous to diagnose by means of needle biopsy because of malignant cell implantation. We recommend that firstly the surgical treatment should be carried out for malignant mesothelioma, which needs extended resection for preventing its recurrence.

Humans↗
PubMed1992

[The surgical treatment for the Stanford type A aortic dissection].

Twenty-nine patients who underwent operation at Shinshu University Hospital for the Stanford type A dissecting aneurysm were analysed. The patients were operated on in the acute stage within 2 weeks after onset. In 13 of these 26 acute cases, the graft replacement of the ascending and arch of the aorta was performed (group A). The patients were operated under a separate perfusion to the brain and the distal anastomosis to the proximal portion of the descending aorta was performed using the method of open distal anastomosis. In other 13 cases, the graft replacement of the ascending aorta was performed (group B). Operative mortality rate was 19% in this series (group A: 23%, group B: 15%). There was no significant difference in their operative mortality of acute stage. And there was also no significant difference in their post operative course of acute stage operations. We concluded that the graft replacement of the ascending and arch of the aorta was better than the graft replacement of the ascending aorta alone for the patients with Stanford type A acute aortic dissection.

Aged↗