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Biomedical subjects

K Isobe

Publications and source records attributed to K Isobe.

At least 163 records · Page 9Linked to original sources
PubMed1995

Cell type-oriented differential modulatory actions of saikosaponin-d on growth responses and DNA fragmentation of lymphocytes triggered by receptor-mediated and receptor-bypassed pathways.

We examined the immunoregulatory action of saikosaponin-d (SSd), which was isolated from the root of Bupleurum talcatum L. and had a steroid-like structure, on murine thymocytes, and compared the action with that on spleen cells. Constitutive DNA synthesis or the growth response stimulated with anti-CD3mAb of thymocytes were down-regulated by 3 micrograms/ml SSd, whereas with spleen cells these were up-regulated by the same concentration of SSd. On the other hand, 3 micrograms/ml of SSd greatly up-regulated the growth response and interleukin 2 (IL-2)/interleukin 4 (IL-4) production induced through a receptor-bypassed pathway by calcium ionophore A23187 plus phorbol 12-myristate 13-acetate (PMA) in thymocytes, whereas it only slightly up-regulated them in spleen cells. Moreover, the same concentration of SSd inhibited DNA fragmentation in thymocytes induced by A23187 or PMA. These results suggest a unique cell type-dependent immuno-modulatory action of SSd.

Animals↗
PubMed1995

Oncogene-linked in situ immunotherapy of pre-B lymphoma arising in E mu/ret transgenic mice.

We attempted to induce anti-tumour immunity for rejecting pre-B lymphoma derived from E mu/ret transgenic mice (TGM). We established pre-B-lymphoma cell lines of C57BL/6 x Balb/c background (H-2b/d) into which H-2k alloantigen and C3H background were introduced (retL1-6 and retL6-6), and we inoculated BCF1 mice with these immunising tumour cells. After these tumours were rejected by alloantigen (H-2k/C3H background)-specific effector cells, the mice were challenged with the pre-B-lymphoma cell line derived from the original E mu/ret TGM (ret0-2). All non-immunised control mice died within 80 days, whereas half the immunised mice survived for over 300 days. The immunity was also effective against primary pre-B-lymphoma cells from E mu/ret TGM and the ret-driven melanoma cell line (MEL-ret), but not against the pre-B-lymphoma cell line from E mu/myc TGM. This immunity was at least in part mediated by cell-mediated cytotoxicity that was specific to the ret oncogene product or ret-regulated antigen. Next we immunised E mu/ret TGM by inoculating them with retL6-6 cells once every 2 weeks beginning at the age of 1 month. Interestingly, this immunisation enabled the TGM to survive longer than the non-immunised control group (P < 0.05). Moreover, 2 of 11 transgenic mice receiving such immunisation were free from both macroscopic and microscopic tumours at the time when all of the 12 non-immunised control TGM had died from their tumour. This provides a new model for oncogene-linked immunotherapy research.

Animals↗
PubMed1995

Reinnervation of peripheral nerve segments implanted into the hemisected spinal cord estimated by transgenic mice.

We investigated how far Schwann cells, which are the peripheral nerve elements supporting axonal regrowth, penetrate into the hemisected recipient spinal cord. C57BL/6 mice, which carry carcinoembryonic antigen as transgene, were used for transplantation study. These CEA transgenic mice were syngenic to C57BL/6 mice except for the expression of human CEA DNA. In the syngenic transplantation study, C57BL/6 mice were transplanted with the sciatic nerve of CEA-transgenic mice to the hemisected spinal cord. Schwann cell migration into the recipient spinal cord was detected by the PCR method. Transplanted Schwann cells migrated into the recipient spinal cord both rostrally and caudally at a distance of 2 mm from the graft-host interface until 21 days after transplantation. At 28 days after transplantation, the Schwann cells migrated rostrally at a distance of 2 mm and caudally at a distance of 4 mm. C57BL/6-CEA sciatic nerve was transplanted to BALB/C mice as the allogenic transplant. CEA DNA was detected until 14 days after transplantation, but disappeared at 21 days. In addition, C57BL/6-CEA sciatic nerves were transplanted into Wistar rats to study xenogenic transplantation. The CEA band disappeared at 10 days after transplantation. In conclusion, by using CEA transgenic mice and the PCR method, we could evaluate the mobility of Schwann cells which are thought to play an important role in axonal regeneration.

Animals↗
PubMed1995

Effect of calcium antagonist, nicardipine, on cerebral blood flow in postasphyxial newborn piglets.

An experiment was carried out in nine piglets within 24 h after birth (control group: four, nicardipine group: five) for the purpose of evaluating the effects of a calcium antagonist, nicardipine, on cerebral blood flow changes induced by asphyxia neonatorum. Under respiratory control with a mechanical ventilator, the animals were exposed to hypoxia. The inspiratory oxygen level was lowered at 15 min intervals from 0.08 to 0.06 and then to 0.05. When bradycardia (heart rate; 60/min or less) was observed, 100% oxygen, adrenaline, and sodium bicarbonate were administered for resuscitation. Nicardipine was administered at a dosage of 10 micrograms/kg via bolus injection 30 min after the resuscitation. It was administered thereafter at a rate of 10 micrograms/kg per h. The cerebral blood flow was measured using a laser Doppler velocimeter. The cerebral blood flow, electroencephalograph (EEG), blood pressure, and heart rate were continuously measured for 120 min after the resuscitation. In the control group, the mean arterial pressure 35 min after the resuscitation was 60 mmHg or more. However, the cerebral blood flow was lower than the prehypoxia value in the animals with a mean arterial pressure of 75 mmHg or less. In the nicardipine group, the mean arterial pressure was lower, but the cerebral blood flow was higher than the prehypoxia value and cerebral ischemia was not induced. The mean arterial pressure 120 min after the resuscitation was 72.0 +/- 8.2 mmHg in the control group, while it was 56.7 +/- 7.5 mmHg in the nicardipine group. It was significantly lower in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Hepatitis C virus infection and genotypes in Japanese hemophiliacs.

Liver function and antibodies to hepatitis C virus and to human immunodeficiency virus-1 were examined in 195 Japanese patients with hemophilia. One hundred and seventy-three were positive for antibody to HCV and 61 for antibody to human immunodeficiency virus-1. In 63 patients, we examined HCV genotypes according to the double polymerase chain reaction method. Forty cases (63%) were infected with hepatitis C virus with a single genotype, including type 1a in five, type 1b in 21, type 2a in seven and type 2b in seven; 16 (25%) were infected with double genotypes, including types 1a + 1b in 14, types 1b + 2a in one and types 1b+2b in one; and four (6%) were infected with triple genotypes, including types 1a + 1b + 2b in two. Genotype could not be determined in three patients by this method. In the 191 nonhemophiliac patients with chronic hepatitis C, HCV genotyping was as follows: type 1a in 0, type 1b in 121, type 2a in 40 and type 2b in 10 of 171 cases (89.5%) with single infection and types 1b + 2a in five and types 2a + 2b in one of six (5.5%) with double infection. In the remaining 14 patients, genotype could not be determined. Frequent transfusion of domestic and/or imported coagulation factor concentrates probably caused the high incidence of HCV infection with rare or mixed genotypes in Japanese hemophiliacs.

Adolescent↗
PubMed1995

Promotion of cytotoxic T-cell generation in mixed leukocyte culture by phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis.

Phosphatidylinositol-specific phospholipase C (PIPLC) from Bacillus thuringiensis, which cleaves phosphatidylinositol or glycosylphosphatidylinositol on the external cell surface to generate a second messenger for intracellular signal transduction (S. Rahman et al., FEBS Lett. 303:193-196, 1992), was found to preferentially promote the generation of alloantigen-specific cytotoxic T lymphocytes in mixed leukocyte culture. PIPLC affected an early stage of cytotoxic T-lymphocyte activation in culture, and there was no evidence of any soluble cellular mediators of this PIPLC action. PIPLC neither enhanced overall cell proliferation nor noticeably promoted interleukin-2 and -4 production in mixed leukocyte culture. The relative population size of Ly-2+ T cells was increased, however, in a late mixed leukocyte culture with PIPLC. In addition, PIPLC enhanced an anti-CD3 monoclonal antibody-induced early increase in [Ca2+]i. These results suggest a new parasite (bacterium)-oriented mechanism for enhancing antigen-driven host cytotoxic T-lymphocyte immunity which does not include promotion of interleukin-2 production.

Animals↗
PubMed1995

Enhancement of nitric oxide production from activated macrophages by a purified form of ginsenoside (Rg1).

We studied the actions of purified ginsenosides Rg1 and Rb1 on nitric oxide production from macrophages and a macrophage cell line RAW264-7. Although neither Rg1 nor Rb1 induced nitric oxide from resting macrophages, Rg1 enhanced the production of nitric oxide from IFN-gamma activated-macrophages or RAW cells. Rg1 also enhanced the production of nitric oxide from macrophages cocultured with nonadherent spleen cells stimulated by conA, LPS or anti-CD3. Rb1, however, did not significantly enhance nitric oxide production from stimulated macrophages or RAW cells. Rg1 enhanced the tumor cell killing by nitric oxide produced from IFN-gamma-activated macrophages.

Animals↗
PubMed1995

Oxidation of ethylene glycol and glycolic acid by glycerol oxidase.

A glycerol oxidase from Aspergillus japonicus oxidized ethylene glycol to glyoxal by the same reaction pathway as alcohol oxidases from methanol yeast. The optimum pH and temperature for the oxidation of ethylene glycol were around 7.0 and 40 degrees C, respectively. Those of glycolaldehyde were similar to those of ethylene glycol. The apparent Kms for ethylene glycol and glycolaldehyde were 195 and 48.8 mM, respectively. The maximum velocities for ethylene glycol and glycolaldehyde were 89.1 and 62.2 mumol/min/mg of protein, respectively. Glycerol oxidase also oxidized glycolic acid, which is not oxidized by the alcohol oxidases, to glyoxylic acid like glycolate oxidases from green plants, and the apparent Km and Vmax for glycolic acid were 114 mM and 2.68 mumol/min/mg of protein, respectively. The glycerol oxidase was applicable to the production of glyoxal and glyoxylic acid.

Ethylene Glycol↗
PubMed1995

The role of a complement regulatory protein in rat mesangial glomerulonephritis.

The host cells are protected from the indiscriminate attack of homologous complement by the membrane-associated complement regulatory proteins. A mouse monoclonal antibody (mAb) 512 (immunoglobulin G1 subclass) has recently been described that recognizes and inhibits the function of a rat complement regulatory protein, a rat homologue of mouse Crry/p65. The aim of this work is to assess the role of a complement regulatory protein (512Ag) recognized by mAb 512 in the complement-dependent glomerular injury induced by mAb OX7 against rat Thy-1.1. For the induction of mesangial injury, the left kidney of a rat was perfused with a combination of OX7 and 512 and the perfusate was discarded from the renal vein (Group I). After the renal artery and vein were restored, the left kidney was connected to the systemic circulation. Rats were euthanized 3 h, 2 days, and 14 days later. Rats perfused either with OX7 (Group II) or with 512 (Group III) or with vehicle only (Group IV) were used as controls. At 3 h, rats of Group I showed more prominent cellular infiltration and mesangial lysis and more C3 deposition in the glomeruli than rats of Group II. Rats of Groups III and IV showed no significant changes. At Day 2, there was still significant mesangial lysis and leukocyte infiltration in Group I rats, whereas rats in other groups showed an almost normal appearance. Glomerular injury in Group I rats returned to normal by Day 14.

Animals↗
PubMed1995

[Expression of mRNAs coding for catecholamine synthesizing enzymes in human adrenal pheochromocytoma].

Pheochromocytomas synthesize and release catecholamines, which subsequently are related to various clinical manifestations of the disease. However, pheochromocytomas are not innervated and the catecholamine release and synthesis are not initiated by neural impulses. It is still unknown how catecholamine synthesis is regulated in pheochromocytomas. As a first step toward understanding the molecular mechanisms by which catecholamine synthesis is controlled in the tumor, we measured the levels of mRNA coding for the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH) and catecholamines in 6 pheochromocytomas and 2 normal adrenal glands. The TH mRNA level was overexpressed and the catecholamine contents were high in 4 out of 6 pheochromocytomas. There was a close correlation between the TH mRNA level and the catecholamines content in the tumors. We also examined the gene expression of the messengers of other catecholamine synthesizing enzymes, dopamine beta-hydroxylase (DBH) and aromatic 1-amino acid decarboxylase (AADC) in pheochromocytomas. The expression of these genes was in parallel with that of TH mRNA in the tumors. These findings indicate that catecholamine overproduction in pheochromocytomas is mediated by the overexpression of genes coding for catecholamines synthesizing enzymes, TH, DBH, and AADC.

Adrenal Gland Neoplasms↗
PubMed1995

In vivo effects of hyperglycemia on the outcome of acute mesangial injury in rats.

To assess the effects of high blood glucose concentration on glomerular changes after the acute mesangial cell injury in the rat, the monoclonal anti-Thy1.1 antibody OX-7 was injected into streptozoticin-induced diabetic rats or normal rats. The increase in proliferating cell nuclear antigen-positive cells in glomeruli at day 4 and glomerular hypercellularity at day 18 was less prominent in diabetic rats than in normal rats. The expansion of mesangial matrix area assessed by fibronectin immunostaining was more prominent, and segmental glomerulosclerosis was observed at day 60 in the diabetic rats. These data suggest that the insulin-deficient group may reflect impaired "wound-healing," leading to the prolonged ECM accumulation under the hyperglycemic condition in vivo.

Acute Disease↗
PubMed1995

[Whole mediastinal irradiation with or without entire hemithoracic irradiation for invasive thymoma].

We retrospectively reviewed the case histories of 45 patients with invasive thymoma who underwent postoperative or definitive radiotherapy. Patients in stage II or stage III were classified according to the treatment volume as follows: a) those who received irradiation confined to the primary tumor site with a generous margin (involved field group, n = 17) and b)those who received prophylactic whole mediastinal irradiation with or without entire hemithoracic irradiation (prophylactic group, n = 21). Seven recurrences were observed among the involved field group, while all patients in the prophylactic group were relapse-free and alive after a median follow-up interval of 50 months. Major side effects were observed in two patients who received entire hemithoracic irradiation. One developed severe pneumonitis resulting in lung fibrosis that required hospitalization, while the other developed nephrotic syndrome of unknown cause. We conclude that whole mediastinal irradiation with or without entire hemithoracic irradiation can be used as a treatment of choice for postoperative invasive thymoma.

Adult↗