Biomedical subjects

F Kimura

Publications and source records attributed to F Kimura.

At least 19 recordsLinked to original sources

PubMed1996

Tumor vaccination with macrophage colony-stimulating factor-producing Lewis lung carcinoma in mice.

Expression of various cytokines by cytokine gene-transduced tumor cells has been shown to increase antitumor immunity of tumor-bearing hosts. In the present study, macrophage-colony stimulating factor (M-CSF) cDNA was retrovirally transfected into Lewis lung carcinoma cells (3LL) of C57BL/6 mouse origin, and the effects of M-CSF expression were studied by inoculating syngeneic C57BL/6 mice with M-CSF-expressing 3LL cells. The mice inoculated with the lowest M-CSF-producing 3LL clone showed significant prolongation of the survival compared with wild-type 3LL-Inoculated mice, and 70% or more of the mice inoculated with 3LL clones with higher M-CSF production rejected inoculation. Mice injected with radiation-inactivated M-CSF-expressing 3LL cells before or after Inoculation of wild-type 3LL cells showed prolonged survival compared with mice injected with radiated control 3LL cells before or after transplantation of wild-type cells. In vivo depletion of effector subpopulations by injection of antibodies against CD4+ T cells, CD8+ T cells, or natural killer (NK) cells suggested involvement of NK cells and CD4+ T cells in M-CSF-mediated antitumor cytotoxicity in M-CSF-producing 3LL cells-inoculated mice. Severe combined immunodeficiency (SCID) mice with defective T- and B-cell function showed prolonged survival duration after inoculation with M-CSF-expressing 3LL cells compared with those transplanted with control 3LL cells, and this effect of M-CSF expression by 3LL-cells in SCID mice was also abolished by in vivo depletion of NK cells by antibody injection. These findings together with the previous reports that M-CSF augments antibody-dependent and-independent antitumor cytotoxicity suggest that M-CSF induces tumor immunity in this cytokine-expressing tumor-transplantation model.

Animals↗

PubMed1996

Vaccination of tumor cells transfected with the B7-1 (CD80) gene induces the anti-metastatic effect and tumor immunity in mice.

The present study demonstrates that the transfection of B7-1 or its variant MB7-2 genes into MHC class I+ tumor cells (B16-BL6 or K1735-M2 melanoma) resulted in the remarkable reduction of lung metastasis caused by i.v. injection into immunocompetent syngeneic mice. However, i.v. injection of the transfectants into T cell-deficient nude mice did not affect reduction of lung tumor colonies as compared with parental wild-type tumors, suggesting that such an inhibitory effect was closely associated with T cell-mediated responses. The reduced metastasis of B7+ tumor cells consequently led to the significant prolongation of survival. Expression of B7 on tumor cells did not influence the tumorigenicity in vivo and tumor cell invasion into basement membrane Matrigel in vitro. We also found that immunization of X-irradiated B7 transfectants was effective as a tumor vaccine for preventing lung metastasis caused by i.v. injection of B7- parental B16-BL6 cells but not against other syngeneic 3LL tumors. Thus, the B7-mediated anti-metastatic effect was tumor-specific. Vaccinations of irradiated B7+ tumor cells before and after surgical excision of the s.c. inoculated primary B7- tumors on day 21 achieved effectively the prevention of spontaneous lung metastasis. Our report that vaccination of irradiated B7+ tumor cells led to a therapeutic effect in an established tumor metastasis model clearly expands and confirms previous related observations.

Animals↗

PubMed1996

Medial septal injection of naloxone elevates acetylcholine release in the hippocampus and induces behavioral seizures in rats.

The effects of injections of naloxone, a universal opioid receptor antagonist, into the medial septal nucleus on hippocampal acetylcholine (ACh) release and behavior were investigated in freely moving rats by means of the microdialysis method. The injection of naloxone (2, 10 and 20 micrograms) produced a marked increase in hippocampal ACh release in a dose-dependent manner. These effects of naloxone were reversed by the post-injection of [D-Ala2, N-Me-Phe4, Gly-ol]-enkephalin (DAGO; 10 micrograms), an opioid mu receptor agonist. Furthermore, basal release of hippocampal ACh was significantly reduced by the injection of DAGO alone. It was also found that rats given an injection of naloxone showed an increase in motor activity and occasionally exhibited behavioral seizures. These effects of naloxone were also reversed by the post-injection of DAGO. The present results suggest that endogenous opioids ionically inhibit the activity of septo-hippocampal cholinergic neurons via mediation of mu opioid receptors in the medial septal nucleus. They also suggest that endogenous opioids modulate the incidence of seizures, at least in part, through opioid mu receptors in the medial septal nucleus.

Acetylcholine↗

PubMed1996

Impairment of maze learning in rats following long-term glucocorticoid treatments.

The present study examined the influence of long-term glucocorticoid treatment on a maze learning task on a radial 8-arm maze in rats. Either 100 mg cholesterol (as a control), or corticosterone, bead was implanted in rats for a period of 3 months, beginning at 12 weeks of age. The effect of this treatment on the maze learning task was evaluated during or 4 weeks after the treatments. In both experiments, corticosterone-implanted rats showed an increase in number of trials to attain at least seven correct choices in the first eight choices in five consecutive trials (P < 0.05). We concluded that long-term glucocorticoid exposure resulted in an impairment of the hippocampal functions, i.e. learning and memory, similar to that found in aged hippocampus.

Animals↗

PubMed1996

Reduced hepatic acute-phase response after simultaneous resection for gastrointestinal cancer with synchronous liver metastases.

Serum cytokines and hepatic acute-phase responses were studied in seven patients undergoing simultaneous resection of primary gastrointestinal cancer and synchronous metastatic liver tumours and in 12 undergoing partial hepatectomy alone for metachronous hepatic metastases. The incidence of postoperative infectious complications was significantly higher after simultaneous resection than after partial hepatectomy alone (P < 0.05). Although the peak interleukin 6 level was significantly higher after simultaneous resection (P < 0.05), plasma levels of acute-phase proteins were significantly lower (P < 0.05). The results suggest that simultaneous resections further reduce the hepatic acute-phase response and render patients liable to infection compared with partial hepatectomy alone, and result in a higher incidence of postoperative infective complications.

Acute-Phase Proteins↗

PubMed1996

Age-related changes in diurnal acetylcholine release in the prefrontal cortex of male rats as measured by microdialysis.

Extracellular levels of acetylcholine in the prefrontal cortex were measured using the micro-dialysis method in freely moving young (three to four months old) and old (23 to 24 months old) male rats over a period of 24 h to examine the effect of aging on prefrontal acetylcholine release. Prefrontal acetylcholine release during a 24 h period exhibited a diurnal variation with higher levels during the dark cycle than during the light cycle in young rats but not in old rats. In addition, prefrontal acetylcholine release was closely associated with spontaneous activity in young rats but not in old rats. The present study suggests that aging reduces diurnal changes in the prefrontal acetylcholine release and that there is a cross-correlation between the prefrontal acetylcholine release and spontaneous locomotor activity in male rats.

Acetylcholine↗

PubMed1996

Fas ligand in human serum.

The Fas ligand (FasL), a member of the tumor necrosis factor family, induces apoptosis in Fas-bearing cells. The membrane-bound human FasL was found to be converted to a soluble form (sFasL) by the action of a matrix metalloproteinase-like enzyme. Two neutralizing monoclonal anti-human FasL antibodies were identified, and an enzyme-linked immunosorbent assay (ELISA) for sFasL in human sera was established. Sera from healthy persons did not contain a detectable level of sFasL, whereas those from patients with large granular lymphocytic (LGL) leukemia and natural killer (NK) cell lymphoma did. These malignant cells constitutively expressed FasL, whereas peripheral NK cells from healthy persons expressed FasL only on activation. These results suggested that the systemic tissue damage seen in most patients with LGL leukemia and NK-type lymphoma is due to sFasL produced by these malignant cells. Neutralizing anti-FasL antibodies or matrix metalloproteinase inhibitors may be of use in modulating such tissue damage.

Animals↗

PubMed1996

Cyclic change of cytokines in a patient with cyclic thrombocytopenia.

The serial change of various cytokines in the serum from a patient with cyclic thrombocytopenia is described. Interleukin 7, stem cell factor, and transforming growth factor beta 1 synchronized with the platelet count, and there was a significant positive correlation between the three cytokines and the platelet count. Levels of macrophage colony-stimulating factor, thrombopoietin, platelet-associated IgG and erythropoietin changed reciprocally with the platelet count, and there was a significant negative correlation between the platelet count and these cytokines except erythropoietin. No cyclic change was observed in IL-3, IL-6, IL-11, granulocyte-macrophage colony-stimulating factor, or leukaemia inhibitory factor. These observations suggest that this disease involves two cyclic changes: megakaryocytopoiesis and platelet destruction, in both of which the cytokines play an important role.

Adult↗

PubMed1996

An aggressive nasal lymphoma accompanied by high levels of soluble Fas ligand.

Fas ligand (FasL), either in the membrane bound form or soluble form, has cytotoxic activity against Fas-expressing cells. We report a case of nasal lymphoma accompanied by liver damage and pancytopenia. The serum level of soluble FasL (sFasL) was very high on admission, but rapidly decreased to normal levels after chemotherapy for lymphoma. Liver damage and pancytopenia also improved with the decrease in serum sFasL. Since Fas is expressed on both hepatocytes and haemopoietic cells, these facts suggest that FasL was expressed on lymphoma cells and directly associated with pathogenesis of liver damage and pancytopenia through its cytotoxic activity.

Enzyme-Linked Immunosorbent Assay↗

PubMed1996

Thoracic aortic aneurysm and aortic dissection: new endoscopic mode for three-dimensional CT display of aorta.

Three-dimensional (3D) endoscopic-mode software was used at helical computed tomography (CT) to evaluate distal aortic arch aneurysms (n = 12) and aortic dissections (n = 10); images were compared with two-dimensional (2D) axial source images. In distal aortic arch aneurysms, the 3D endoscopic mode depicted the relationship of the arterial orifices and the aneurysm, which is difficult to evaluate with 2D axial images alone. In aortic dissections, however, the 3D endoscopic mode did not provide additional information to that provided on the 2D axial source images.

Aged↗

PubMed1996

Increased serum interleukin-6 level and reduction of hepatic acute-phase response after major hepatectomy.

It has been proposed that a major hepatectomy impairs the liver-related host defense mechanism. The changes in the levels of serum inflammatory cytokines and plasma acute-phase proteins synthesized in the liver were measured after partial hepatectomy. Peak levels of serum interleukin-6 were significantly higher after extended lobectomy than after lobectomy or segmentectomy (p < 0.01). Serum interleukin-1 beta and tumor necrosis factor alpha levels showed no significant changes. Plasma levels of acute-phase proteins were significantly lower after lobectomy or extended lobectomy (p < 0.05). A reduced hepatic acute-phase response probably renders patients liable to infection after major hepatectomy.

Acute-Phase Proteins↗

PubMed1996

A quantitative analysis of testosterone action on FSH secretion from individual pituitary cells using the cell immunoblot assay.

We investigated the effects of testosterone on FSH secretion from male rat anterior pituitary cells in culture at the single cell level. Anterior pituitary cells cultured with or without 10 ng/ml testosterone for 72 h were mono-dispersed and subjected to cell immunoblot assays for FSH. Cell blots specific for FSH were quantified by means of a microscopic image analyzer. The number of FSH-secreting cells detected as immunoreactive cells blots on the transfer membrane represented 4.1% of total pituitary cells applied on the membrane. The amount of FSH secreted by single cells varied from < 20 to > 8,000 fg/cell/h. The number of FSH-secreting cells was not changed by the addition of 10 ng/ml testosterone into the culture medium. Testosterone administration increased the mean FSH secretion by 64% after 3 h incubation, resulting in a shift to the right in the frequency distribution of FSH secretion from single cells. The total amount of FSH, namely the sum of FSH secreted by each FSH-secreting cel, was increased by 92% by the addition of testosterone. However, mean amounts of FSH secretion by the top ten cells of the largest secretor subgroup (> 5 pg/cell/3 h) were not different between control and testosterone-treated groups. The present study analyzed, for the first time, FSH secretion from rat anterior pituitary cells at the single cell level. The results suggest that stimulation by testosterone of FSH secretion in vitro is not due to an increase in the number of FSH-secreting cells but to an increase in FSH secretion from each cell.

Animals↗

PubMed1996

Increased levels of human hepatocyte growth factor in serum and peritoneal fluid after partial hepatectomy.

OBJECTIVE/METHOD: It has been reported that inflammatory cytokines up-regulate human hepatocyte growth factor synthesis in vitro. To demonstrate the relation of this growth factor to interleukin-6 and tumor necrosis factor alpha, the changes in the levels of these cytokines were measured in serum and peritoneal fluid in 22 patients after partial hepatectomy. RESULTS: Serum and fluids levels of cytokines showed a maximum within 3 days after surgery. Cytokines concentrations were much higher in fluid than in serum (p < 0.05). The maximum serum levels of human hepatocyte growth factor were significantly correlated with those of interleukin-6, intraoperative blood loss, and operating time (p < 0.05) but not resected liver weights. In fluid level, the growth factor was also correlated with interleukin-6 (p < 0.05) but with tumor necrosis factor alpha. CONCLUSIONS: These results suggest that human hepatocyte growth factor might be locally produced in the injured tissue associated with interleukin-6 and independently of resected liver weights.

Aged↗

PubMed1996

Low-dose melphalan for treatment of high-risk myelodysplastic syndromes.

Twenty-one consecutive patients with high-risk myelodysplastic syndromes (MDS) including six with refractory anemia with excess blasts (RAEB) and 15 with RAEB in transformation (RAEBt) were treated with daily oral low-dose melphalan (2 mg/day). Seven patients achieved complete remission (CR), one patient partial response, and four minor response while the remaining eight did not respond. The median age of the patients was 65 (range 56-83 years). The mean total amount of melphalan given was 140+/-19 mg in patients who achieved CR. The median duration of CR was 14.5 months. Serious toxicity was not encountered in any of the cases. Neither marrow suppression nor pancytopenia was observed during the administration of melphalan in patients who achieved CR. The clinical features of CR patients included normal karyotype and hypocellular marrow in biopsied specimen from the lilac bone. These observations suggest that melphalan may exert some differentiation effects on leukemic cells in addition to cytotoxic effects. Our study indicates that daily administration of low-dose melphalan is worth trying in the treatment of elderly patients with high-risk MDS.

Aged↗

PubMed1996

Augmentation of antitumor immunity using genetically M-CSF-expressing L1210 cells.

Macrophage colony-stimulating factor (M-CSF) enhances tumoricidal activities of macrophages. We transduced human M-CSF cDNA into the mouse lymphoid cell line, L1210, and examined the antitumor effect of the locally expressed M-CSF. Mice injected with the M-CSF-producing subline showed improved survival in comparison with the mock-transfected cell line or parental cell line plus M-CSF administration (20 microg/kg for 3 days) at inoculated cell numbers of 10(2) or 5 x 10(3). The survival rate at 50 days after injection of 10(6) high M-CSF-expressing cells was 80%, significantly higher than that after injection of the mock-transfected cells, which killed all the mice by day 23. The survival rate appeared to depend on the amount of M-CSF produced. Moreover, all surviving mice after intravenous injection of the M-CSF-expressing sublines were rechallenged with 10(6) parental L1210 cells at day 50, and all survived up to day 100, demonstrating that M-CSF-expressing cells induced immune protection against the parental cells. The same improvement of survival was observed in mouse M-CSF-expressing cell lines. These observations imply that M-CSF cDNA is a candidate gene for use in gene therapy in leukemia.

Animals↗

PubMed1996

[Histopathological prognostic factors in 146 patients with renal cell carcinoma: comparison between incidental and non-incidental cases].

To characterize the prognostic factors among pathological structural pattern, cell type, infiltration, and incidental or non-incidental renal cell carcinoma (RCC), we reviewed the records of 146 patients with RCC who underwent nephrectomy at our institute. The patients were 26 to 86 years old (mean age 58). The men-to-women ratio was 3.2:1. The tumor originated in the right kidney in 83 patients and in the left in 63. The solid pattern was associated with poorer survival than other patterns (p < 0.01). Spindle or pleomorphic cell type had poorer survival than common type (p < 0.01). The number of incidentally discovered RCC has increased since 1986, and survival is better than in non-incidental RCC, because of smaller tumor size, low stage tumor (stages 1, 2; 83.6%), and fewer papillary or solid type. In addition, there were no spindle or pleomorphic cell type, grade 3 or INF gamma-positive case. Survival is good even when the tumor is large.

Adult↗

PubMed1996

[Difficult tracheal intubation and abnormal response to thiopental in a patient with arthrogryposis multiplex congenita].

Anesthesia was administered for six times to a patient with arthrogryposis multiplex congenita (AMC) at the age of 10 to 17 years. In the first four occasions of anesthesia, difficult tracheal intubation was encountered due to limited neck extension, inadequate mouth opening and the short epiglottis. On the fifth anesthesia, the patient remained conscious even after intravenous injection of thiopental 6.6 mg.kg-1, and enflurane in combination with nitrous oxide was administered to induce anesthesia. During the induction of the sixth anesthesia, excessive oral secretion and severe continued nausea were observed just after intravenous administration of thiopental 5.3 mg.kg-1. These were overcome by intravenous administration of ketamine 2.0 mg.kg-1. Problems such as difficulty in tracheal intubation and abnormal response to thiopental need special attention in patients complicated with AMC, particularly during induction of anesthesia.

Abnormalities, Multiple↗

PubMed1996

Acute immobilization stress and intraventricular injection of CRF suppress naloxone-induced LH release in ovariectomized estrogen-primed rats.

The present study was undertaken to evaluate the role and possible interaction of the endogenous opioid peptide (EOP) and corticotropin-releasing factor (CRF) in the acute stress-induced suppression of gonadotropin secretion in ovariectomized estrogen-primed rats. An intravenous (i.v.) injection of naloxone (10 or 20 mg/kg), an EOP antagonist, significantly elevated serum luteinizing hormone (LH) levels within 10 min in non-stressed animals. The naloxone-induced LH release was completely eliminated when tested 30 min after the onset of acute immobilization. In a subsequent study, it was found that suppression of the naloxone-induced LH release occurred as early as 5 min after the stress onset, and was still evident 60 min after the end of a 30-min period of immobilization. The effect of naloxone was restored 3 h after liberation of the animal from the 30-min immobilization. An intraventricular (i.c.v.) injection of CRF (1 or 5 micrograms) also significantly suppressed, in a dose-related manner, the effect of a subsequent i.v. injection of naloxone. However, an i.c.v. injection of alpha-helical CRF(9-41) (25 or 50 micrograms), a CRF antagonist, prior to immobilization, could not interfere with the suppressive effect of stress on naloxone-induced LH release. These results suggest that both acute immobilization stress and CRF can inhibit the LH secretory activity without mediation by EOP neurons. However, the stress-related suppression may involve non-CRF mechanism(s).

Analysis of Variance↗