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Biomedical subjects

K Nemoto

Publications and source records attributed to K Nemoto.

At least 181 records · Page 10Linked to original sources

Therapeutic activity of deoxyspergualin in comparison with cyclosporin A, and its combined use with cyclosporin A and prednisolone in highly allogeneic skin transplantation in the rat.

The present paper demonstrates the efficacy of a novel immunosuppressive agent, deoxyspergualin (DSG), in rat skin transplantation despite major histocompatible antigen differences, both by itself and in combination with cyclosporin A (CyA) and prednisolone (PD). DSG significantly prolonged the median survival time (MST) of WKAH skin on F344 rats, when given at daily doses of 1.5-12 mg/kg i.p. for 10 days starting from day one after grafting. A significant increase of the MST has been observed also in the rats orally receiving CyA at daily doses of 12.5-50 mg/kg according to the same dosing protocol. DSG was as effective as CyA in prolonging the MST. In contrast, when treatment started 4 days after grafting (at the time of the rejection crisis), DSG (6 mg/kg) was able to reverse the rejection, whereas CyA (50 mg/kg) was not. When DSG (1.5 mg/kg) and CyA (6.25 or 12.5 mg/kg) were given together from day one after grafting, the combined therapy was superior to each monotherapy. Similarly, when DSG (1.5 mg/kg) and PD (10 mg/kg) were given simultaneously from the rejection crisis, the combined therapy was demonstrated to have stronger activity than any of the monotherapies. Moreover, the skin-allografted rats could be switched successfully either from CyA to DSG treatment or from DSG to CyA treatment.

Animals↗

Intracellular signals in IgG-mediated anaphylactic contraction of single smooth muscle cells.

Single smooth muscle cells from the taenia coli of guinea pigs passively sensitized with anti-egg albumin IgG fraction were used to evaluate the intracellular signal transduction system during anaphylactic contraction. 125I-IgG was bound to single smooth muscle cells, and sensitized smooth muscle cells contracted in response to antigen treatment. In response to neuraminidase treatment, 125I-IgG binding to the cells was decreased, along with an inhibition of anaphylactic contraction. Pretreatment with islet-activating protein (IAP), neomycin, quercetin and H-7 inhibited anaphylactic contraction, whereas pretreatment with phorbol 12,13-dibutylate augmented the contraction. The signal produced by the interaction between IgG bound to the smooth muscle cells and antigen appears to be transmitted to the intracellular contractile element via the signal transduction system involving G protein. Phospholipase-C and -A2 appear to be the effectors in the signal transduction system for anaphylactic contractions. Protein kinase C, activated with reference to phospholipase-C, also may be involved in anaphylactic contraction.

Anaphylaxis↗

[Low-dose rate telecobalt therapy as a boost against esophageal carcinomas].

The results of treatment of 54 esophageal carcinomas managed with low-dose-rate telecobalt therapy (LDRT) as a boost were compared with those of 89 esophageal carcinomas treated with conventionally fractionated irradiation alone (CFI). The LDRT (1 Gy/hr, 5-7 Gy/day, to a total dose of 14-20 Gy) was boosted about 10 days after the CFI dose of 60 Gy. Although the LDRT group included more advanced cases than the CFI group, local effects and survival rate of the LDRT group, especially those with tumorous X-P and serrated types, were better than those of the CFI group. Late complications were more severe in the LDRT group. However, they were acceptable when the total dose in the LDRT group was brought under 80 Gy.

Aged↗

Elevation of nerve growth factor synthesis by constitutive expression of v-src oncogene in cultured rat fibroblasts.

Rat fibroblast 3Y1 cells transformed by Rous sarcoma virus (RSV) or transfected with the v-src gene showed a highly constitutive v-src gene expression. Simultaneously, marked increases in the cellular level of nerve growth factor (NGF) mRNA and NGF content in the culture medium were observed. The levels of NGF mRNA and NGF secreted into the medium were correlated with the expression level of v-src mRNA gene in both transformants and control 3Y1 cells. These results suggest that v-src gene expression is relevant to regulation of NGF synthesis in rat 3Y1 fibroblasts.

Animals↗

Glycolipid changes in murine myelogenous leukemias: neutral glycolipids as markers for specific populations of leukemias.

We have studied the glycolipid composition of six different murine myelogenous leukemias as well as that of T-cell leukemias and normal spleen cells. Neutral and acidic lipid fractions were isolated by column chromatography on DEAE-Sephadex and analyzed by high-performance thin-layer chromatography (HPTLC) and an HPTLC overlay method. Murine myelogenous leukemias were found to contain globo- and ganglio-series neutral glycolipids, e.g., glucosylceramide (Glc-cer), lactosylceramide (Lac-cer), globotriaosylceramide (Gb3), globoside (Gb4), Forssman glycolipid (Gb5), and asialo-GM1 (GA1). Monoblastic leukemia cells contained increased proportions of Gb3, Gb4, Gb5, and GA1. Monocytic and myelomonocytic leukemia cells contained increased proportions of Glc-cer and Lac-cer. Especially, Glc-cer accounted for approximately 60% of the total neutral glycolipids in monocytic leukemia cells. Gb3 was the major neutral glycolipid in reticulum cell neoplasm type A, and it accounted for approximately 75% of the neutral glycolipids. GA1 was the major neutral glycolipid in myeloblastic and granulocytic leukemia cells as well as T-cell leukemias. Especially, granulocytic leukemia cells contained predominantly GA1, and it accounted for approximately 80% of the total neutral glycolipids. The pattern of gangliosides in myelogenous leukemias was more complex when compared with that of the neutral glycolipids; murine myelogenous leukemias contained at least 13 gangliosides, including such major gangliosides as GM1, GM1b containing N-acetyl neuraminic acid and N-glycolyl neuraminic acid, and Ga1NAc-GM1b. Alterations of glycolipid composition in murine myeloid leukemias may be associated with cellular differentiation and maturation, and therefore these characteristic glycolipid species may be regarded as markers for specific populations of leukemia cells.

Animals↗

[Radiotherapy of intracranial germinomas].

Between 1978 and 1988, 28 patients with intracranial germinoma, verified or presumed, were treated with radiation. The diagnosis was made based on histology in 6 cases, on cerebrospinal fluid (CSF) cytology in 2 cases and on clinical (response to radiation) and radiological findings in the remaining 20 cases. The target volume was the primary site plus whole brain in 23 cases, whole brain in 4 cases and the primary site only in 1 case. Whole spinal irradiation was undertaken for 14 patients, including 9 patients of high risk group, i.e., with positive findings in CSF cytology, suspected subarachnoid space seeding, multifocal tumors, infiltration to the ventricular wall or previous surgery for the tumor. The average dose was 52.8 Gy to the tumor, 28.7 Gy to the whole brain and 21 Gy to the spinal axis. Five and ten-years survival rate were 100% and 96%, respectively. No intracranial recurrence or spinal metastasis has been found so far. Therefore no spinal irradiation seems to be unnecessary for non-high risk group of patients. Approximately 20 Gy should be sufficient, if spinal irradiation is to be indicated for high risk group. The dose for the primary tumor and whole brain could have been diminished to 40 Gy and 20 Gy, respectively.

Brain Neoplasms↗

Angiocentric immunoproliferative lesion of the stomach.

We report here a rare case of angiocentric immunoproliferative lesion (AIL) of the stomach. The patient was a 61-year-old Japanese female whose medical history was unremarkable. Following a complaint of abdominal discomfort, a submucosal tumour of the stomach was found and gastrectomy was done. Histological examination of the tumour revealed multiple angiocentric or angiodestructive lesions with numerous lymphocytic infiltrates. These vascular lesions were histologically the same as those in benign lymphocytic vasculitis with granulomatosis (BLV) of the respiratory tract. AIL is a distinct entity, including BLV, lymphomatoid granulomatosis and angiocentric lymphoma with BLV representing a good prognosis group of AIL. A survey of the literature suggests that AIL is a spectrum of T-lymphocyte proliferative disorders. To our knowledge, this is the first case of AIL involving the stomach primarily.

Female↗

Prognostic factors for local control in nasopharyngeal cancer (NPC): analysis by multivariate proportional hazard models.

Despite the development of meticulous radiation therapy techniques, the local control of the nasopharyngeal cancer (NPC) remains unsatisfactory. We examined retrospectively the clinicopathologic factors which have impact upon local recurrence-free survival (LRFS) of the 67 patients with NPC who had been irradiated greater than or equal to 40 Gy with curative intent from 1975 through 1988. Three-year LRFS rate was 63%. T stage, histology, the presence of accompanying lymphocytic infiltration, and the properness of radiation therapy had influence upon LRFS with a statistical significance. Multivariate proportional hazard models showed that T stage and pathology retained significance. Radiation therapy properness emerged as a third factor when only the patients irradiated greater than or equal to 60 Gy were included in the analysis. From these results, three groups with low, moderate, and high risk of shortened LRFS could be separated. This risk classification could contribute to the stratification criteria of future study for the improvement of local control by new modalities.

Adult↗

Transformation of mammalian cells by luteoskyrin.

The transforming activity of luteoskyrin (LS), a bis-anthraquinoid mycotoxin produced by Penicillium islandicum Sopp., and a hepatocarcinogen in rodents, was examined by an in vitro transformation assay using mouse embryonal Balb/3T3 A31-1-1 cells. The results revealed that LS induced type III foci at 0.5 micrograms/ml, and that the cells selected from these foci by soft-agar cloning grew with a high saturation density. Thus, it was confirmed that LS not only induces hepatic tumours in laboratory animals, but also transforms in vitro cultured mammalian cells. The tumorigenicity of the transformants obtained was confirmed by transplantation into nude mice and by image analysis with IIIIn. A transfection assay, using calcium phosphate co-precipitation, demonstrated that the DNA of the cloned cells transformed NIH3T3 cells. Northern blot also revealed transcriptional activation of c-myc and c-Ha-ras oncogenes. The possible participation of LS-derived hydroxy radicals in the formation of genetic lesions was discussed.

Animals↗

Deoxyspergualin in lethal murine graft-versus-host disease.

The beneficial effect of deoxyspergualin (DSG, NKT-01) on lethal graft-versus-host disease in mice has been studied in a major histoincompatible donor-recipient combination. Suppression of the effector mechanisms responsible for the lethal outcome in this GVHD model is also noted. This study reveals: (1) DSG has a marked potential for treatment of lethal GVHD; (2) DSG and methotrexate in combination yield longer survival times than DSG or MTX alone; (3) long-term survivors, following DSG treatment, become stable chimeras as evidenced by cell-surface analysis of spleen cells; and (4) high activity of H-2-reactive cytotoxic T lymphocytes is detected in spleens of the mice with lethal GVHD, whereas natural killer activity is only slightly increased. DSG inhibits CTL activity not only in the induction stage but also in the advanced stage of the disease. These findings indicate that DSG might be beneficial in clinical bone marrow transplantation either alone or in combination with MTX.

Animals↗

Unusual pancreatic tumor resembling solid and cystic tumor, with somatostatin production and aberrant crystalloid structures.

An unusual pancreatic tumor in a middle-aged man is reported. The tumor was a large encapsulated mass with necrosis and hemorrhage, and microscopically, it showed a predominant microcystic pattern with solid pattern areas. The clinical and histological features of this tumor were similar to those of solid and cystic tumor. Immunohistochemical studies showed that the tumor was positive for alpha 1-AT, NSE, CA 19-9 and somatostatin. Electron microscopy studies showed neurosecretory granules, intercellular junctions, annulate lamellae and aberrant crystalloid structures. These findings indicated that the tumor had differentiated into acinar, ductal and endocrine cells, suggesting that solid and cystic tumor originates from multipotential immature cells.

Adult↗

[Treatment of 61 patients with acute myelogenous leukemia at first relapse].

Treatment results in the 61 adult patients with AML in first relapse were analyzed to establish a better strategy for this group of patients. These patients received reinduction chemotherapy during 1979-1988. Complete remission (CR) was obtained in 57.4% of the cases, and the probability of survival and remaining in CR at five years was 11.9% and 17.9%, respectively. The longer duration of initial remission was favorable factor for achieving second CR. Type of reinduction regimens which were different from those used in the initial induction phase did not influence the second CR rate. The use of different consolidation regimen appeared to favorably affect the survival and probability of remaining in CR.

Adult↗

Radiation-induced myeloid leukemia in C3H/He mice and the effect of prednisolone acetate on leukemogenesis.

We found that the incidence of spontaneous myeloid leukemia in C3H/He male mice was less than 1%, but it could be increased considerably by total-body X irradiation. The induction of myeloid leukemia was seen to increase after doses from 0.47 Gy (3%) to 2.84 Gy (23.9%), and then decrease after a dose of 4.73 Gy (13.6%). The administration of prednisolone acetate (synthesized glucocorticoid) after irradiation resulted in a significant increase in the incidence of myeloid leukemia from 23.9 to 38.5% after a dose of 2.84 Gy; however, corticosterone, a glucocorticoid secreted by cells, did not have such an enhancing effect.

Animals↗

[The effects of Cepharanthin on the recovery of hematopoietic stem cells after X-ray irradiation].

Administration of Cepharanthin (ceph) resulted in a significant acceleration of the recovery from leukopenia in 5-Gy X-ray irradiated mice. Then we examined the function of ceph on the recovery of hematopoietic stem cells after irradiation. The number of GM-CFU (granulocyte-macrophage committed stem cells) in the femur and spleen increased significantly in ceph compared to phosphate buffer solution administered groups. However, the time course of the recovery of GM-CFU did not differ between the two groups. These enhancing effects of ceph on GM-CFU were not observed when it was added to a bone marrow culture system. Therefore, the accelerating effects of the recovery from leukopenia after irradiation appears to be an indirect function of ceph.

Alkaloids↗

[Influences of menopause and oophorectomy on sex steroids secretion and metacarpal bone mineral content].

The effects of menopause and oophorectomy (OPX) upon blood levels of sex steroid and bone mineral content were studied in age- and body size-matched postmenopausal subjects (n = 55), OPX subjects (n = 42) and premenopausal controls (n = 35). Blood levels of 17-OH-pregnenolone, 17-OH-progesterone and androstenedione were significantly lower in the OPX group than in the other two groups. For DHEA, DHEA-sulfate and testosterone, there were no significant intergroup differences. The blood level of estrone was the lowest in the OPX group, followed by the postmenopausal group (p less than 0.05). For estradiol, there was no difference between the two groups and its blood level was lower in these groups than in the controls. For LH and FSH, there were no differences between the former two groups, but blood levels were significantly high in these groups (p less than 0.01). Microdensitometric indices such as GS min and sigma GS/D were all low in postmenopausal and OPX groups in comparison with the controls (p less than 0.01). There were no considerable differences in these indices between the former groups. In conclusion, ovarian interstitial cells are still functioning and secrete androgens in short interval of three years after menopause, as known from higher blood levels of androgens and converted estrone in the postmenopausal group than in the OPX group. However, there was no significant difference between these two groups with regard to metacarpal bone mineral content.

Age Factors↗

[Influences of menopause and oophorectomy on bone metabolism and spinal bone mineral content].

The present study was performed on bone metabolism and spinal bone mineral content (BMC) in 3 groups of age- and body size-matched subjects: Thirty-three postmenopausal subjects, 37 oophorectomized (OPX) subjects and 22 premenopausal subjects. Serum levels of Alp and osteocalcin (OC) as indices of bone formation, U-Ca/cr and U-hydroxyproline (Hpr)/cr as indices of bone resorption, and Ca-regulating hormones, M-PTH, calcitonin (CT) and 1,25(OH)2D; were measured and spinal BMC was determined by QCT. Alp and OC levels were slightly higher in the postmenopausal group than in the OPX group and, in contrast, U-Ca/cr and U-Hpr/cr were slightly higher in the latter. The M-PTH level was slightly higher in the latter, and the CT level in the former. There was no difference in the 1,25(OH)2D level between two groups. For BMC, there was no difference between the two groups. The above results corresponded to the previously reported significant reductions in sex steroids. OPX seemed to affect bone metabolism more than menopause, there was no specific influence of OPX on spinal BMC as compared with QCT findings in postmenopausal subjects. Our previous study and the present study demonstrated that, at an interval of about 3 years after menopause or OPX, the endocrine system and bone metabolism tended to be more affected by OPX. However, BMC did not reflect any influence of OPX, or of menopause. There was no clear clinical difference between postmenopausal subjects and the OPX subjects with regard to the osteoporotic condition.

Alkaline Phosphatase↗

[Low-dose-rate teletherapy combined with hyperthermia as a boost therapy].

The efficacy of the low dose rate teletherapy (LDRT; 1 Gy/hr, 4 Gy/day, 2-3 times/week) combined with hyperthermia as a boost therapy (H (+) group) against far advanced carcinomas was examined. The treatment results in H (+) group (17 esophageal carcinomas, 3 pancreatic and bile duct carcinomas and 5 other carcinomas) were compared with the ones in H (-) group (38 esophageal carcinomas, 5 pancreatic and bile duct carcinomas and 13 other carcinomas) which were treated with the LDRT (1 Gy/hr, 7 Gy/day, every day) as a boost. A total dose of 14-24 Gy by the LDRT was followed after the irradiation of 50-60 Gy by conventionally fractionated method (1.5-2 Gy/day). H (+) cases were treated with 42.5 degrees C, 1 hour hyperthermia immediately before the LDRT and 19 cases (76%) were successfully heated. There were no significant differences between H (+) group and H (-) group in local control, late severe complication and survival rates, even when they were corrected by primary sites and stages. The incidence of metastases was higher in H (+) group. It was considered that the gain of the combination of the LDRT and the hyperthermia as a boost therapy was a little.

Adult↗