Biomedical subjects

M Tagawa

Publications and source records attributed to M Tagawa.

At least 127 records · Page 7Linked to original sources

PubMed1996

Inhibition of peritoneal dissemination of colon carcinoma in syngeneic mice immunized with interleukin-2-producing cells.

We have examined the antitumor effect of murine colon carcinoma cells engineered to produce human interleukin-2 (IL-2) in syngeneic mice. Subcutaneous inoculation of retrovirally-transduced cells with IL-2 gene formed small tumors, but they became regressed spontaneously. Consequently, the inoculated mice showed prolonged survival. Histological examination of the tumors derived from IL-2-producers revealed predominant infiltration of macrophages around tumor necrotic masses. Thus, inoculation of IL-2-producing cells could protect the mice from subsequent subcutaneous or intraperitoneal challenges with wild-type cells, suggesting the induction of acquired immunity due to the effect of tumor vaccination.

Animals↗

PubMed1996

Evaluation of the bystander effect in experimental brain tumors bearing herpes simplex virus-thymidine kinase gene by serial magnetic resonance imaging.

Antitumor effects of herpes simplex virus-thymidine kinase (HSV-tk) gene transfer followed by ganciclovir (GCV) administration were studied by serial magnetic resonance imaging (MRI) with reference to the bystander effect. Mixed populations of 9L-gliosarcoma cells transduced with the HSV-tk gene (TK cells) and wild-type 9L cells were implanted into the brain of syngeneic Fisher rats at various ratios (total cell number, 10(5) cells; percentage of TK cells, 100%, 25%, 10%, or 0%). Rats were treated with GCV (30 mg/kg per day) or saline for 14 days and tumor masses were visually monitored using MRI. All of the saline-treated rats (regardless of TK cell percentage) and GCV-treated rats inoculated with 0% TK cells died between day 19 and day 31 (mean survival, 22.9 days) due to progressive tumor growth. The GCV-treated rats inoculated with more than 10% of TK cells lived significantly longer than the saline-treated rats (p < 0.01). The mean survivals of GCV-treated groups were 50.7, 70.0, and longer than 100 days for 10%, 25%, and 100% TK cells, respectively. MRI study revealed that reduction in tumor size and disappearance of tumor were observed in the GCV-treated rats inoculated with 10% or 25% TK cells. Complete regression of the tumor was, however, observed only in the rats implanted with 100% TK cells. The present results show that the bystander effect is clearly observed in vivo in a TK percentage-dependent manner, and a population of more than 25% of TK-positive cells is required for complete tumor elimination.

Animals↗

PubMed1996

Augmentation of in vivo growth of Lewis lung carcinoma cells transduced with granulocyte macrophage-colony stimulating factor gene.

Cloned high-metastatic Lewis lung carcinoma. A11 cells were retrovirally transduced with either granulocyte macrophage-colony stimulating factor (GM-CSF) or beta-galactosidase gene and examined for their tumorigenicity. GM-CSF-engineered A11 cells produced a much higher amount of GM-CSF than the parental and control cells. Unexpectedly, GM-CSF-engineered A11 cells grew more rapidly than the control cells, while in vitro growth rates of these cells were almost the same. The enhanced tumor growth seemed to be unique to GM-CSF among various cytokines, because interleukin 2 (IL-2), interleukin 4 (IL-4) and interleukin 6 (IL-6) producer cells exhibited suppressed tumor growth.

Animals↗

PubMed1996

Association of p53 gene mutation with decreased chemosensitivity in human malignant gliomas.

Loss of p53 function is involved in tumorigenesis of various human cancers, but the relation between mutation of the p53 tumor-suppressor gene and the chemo- and radiosensitivity of tumors remains unclear. Mutated p53 gene in malignant glioma is often associated with progression and recurrence of malignancy, and these events are closely linked with increased resistance to both chemotherapy and radiation. We have examined the status of the p53 gene in malignant gliomas obtained from 34 patients (glioblastoma: 29 cases, anaplastic astrocytomas: 5 cases). The chemosensitivities of these specimens using 28 kinds of anti-cancer agents were determined using an in vitro assay system. Overall, 12 mutated cases of p53 gene were found in malignant glioma samples. The mean numbers of effective agents were 0.58 for the tumor samples with p53 mutations and 5.00 for tumors without mutations. Our data indicate that p53 gene mutation predisposes to decreased cell killing via chemotherapy in malignant gliomas.

Adolescent↗

PubMed1996

Binary expression of olfactory bulb-protein tyrosine phosphatase in rat central nervous system: developmental gene regulation in neonate cerebral cortex and constitutive expression in olfactory-rhinencephalon.

Olfactory bulb-protein tyrosine phosphatase (OB-PTP) is a receptor type PTPase dominantly expressed in olfactory bulb. Previously, we isolated and molecularly cloned a rat OB-PTP cDNA from an embryonal brain cDNA library. In the present study, we investigated its temporal and spatial gene expression by Northern blot and in situ hybridization analysis. The expression of OB-PTP gene was firstly detected in day 16 post coitum embryo and significantly increased during the late-gestational stage, attaining the highest level in the first week of neonate. The OB-PTP transcript was then down-regulated postnatally and was detected barely in an adult brain. In situ hybridization analysis showed that the transcript was characteristically localized in the postmitotic neurons of cerebral cortex and subcortical structures, and was down-regulated by day 28 when the cortical and subcortical structures have been organized. In the olfactory-rhinencephalon system including olfactory bulb and piriform cortex, the OB-PTP was preferentially expressed in the postmitotic neurons, and in contrast continuously expressed in the matured brain. Based on the evidence that DPTP10D, the Drosophila homolog of OB-PTP, is localized in the axons of specific pioneer neurons in Drosophila embryo, the OB-PTP is presumably involved in the axonogenesis of cortical and subcortical neurons as well as olfactory neurons in mammalian central nervous system. The biological significance of transcriptional regulation in olfactory system is discussed in terms of continuous axonal connections by regenerating olfactory neurons.

Animals↗

PubMed1996

Antitumor effect induced by the expression of granulocyte macrophage-colony stimulating factor gene in murine colon carcinoma cells.

Murine colon carcinoma cells which secrete several kinds of cytokine after retroviral transduction with corresponding genes, were examined for their antitumor effects in syngeneic mice. The mice inoculated with granulocyte macrophage-colony stimulating factor (GM-CSF) producer cells showed not only prolonged survival but also reduced tumorigenicity. The antitumor effect caused by the expression of interleukin-4 was less than that of GM-CSF, and interleukin-6 producer cells did not show any effects on the survival of the host animals. Histological examination of the GM-CSF-producing tumor revealed predominant infiltration of neutrophils and necrotic change of the tumor. The present study indicates the feasibility of cancer gene therapy with the expression of GM-CSF gene in tumor cells.

Animals↗

PubMed1996

Murine colon carcinoma cells engineered to produce human interleukin-2 induce tumor-specific anti-tumor response.

Murine colon carcinoma cells (colon 26) transduced by a retrovirus vector with the human interleukin-2 (IL-2) cDNA were studied for their tumorigenicity. Although cell growth in vitro was not affected by integration of the IL-2 gene, s.c. tumors of IL-2-producing colon 26 cells (H2) in syngeneic mice regressed spontaneously after producing small masses. Histological examination of the sites of tumor rejection revealed predominant infiltration of macrophages around the tumor necrotic mass. Subsequent challenge with parent colon 26 cells, but not with Meth A cells (fibrosarcoma of the same genetic background), did not result in tumor formation in mice which had been protected against H2 cells. Inoculation of H2 cells into syngeneic nude mice resulted in tumors with a retarded growth rate. Taken together, T cell-dependent, tumor-specific immunity is obtained by local IL-2 secretion around colon tumors, and this experimental animal model gives us a clue(s) for investigating host anti-tumor responses by cytokine production.

Animals↗

PubMed1996

Enhancement of bone formation by drawn poly(L-lactide).

Poly(L-lactide) (PLLA) was molded into films and rods, and drawn in the longitudinal direction to endow them with piezoelectricity. The piezoelectric constants of PLLA films increased with the draw ratio and, after passing a maximum at a draw ratio around 5, decreased. PLLA samples with a draw ratio 5 underwent fibrilization. The PLLA rods were intramedullarily implanted in the cut tibiae of cats for internal fixation up to 8 weeks. Fracture healing was clearly promoted with increased callus formation as the draw ratio of the PLLA rod increased, whereas the undrawn PLLA as well as a polyethylene control rod had no effect on callus formation, or rather, retarded it. This finding strongly suggests that the promotion of fracture healing by fixation with drawn PLLA can be ascribed to the piezoelectric current generated by the strains accompanying leg movement.

Animals↗

PubMed1996

Gene expression and active virus replication in the liver after injection of duck hepatitis B virus DNA into the peripheral vein of ducklings.

BACKGROUND/AIMS: Duck hepatitis B virus is a member of the hepadnavirus family, which possesses strong hepatotropism. Duck hepatitis B virus DNA serves as a replicative template for producing biologically active virus particles after transfection into cell lines established from human hepatocellular carcinoma or into duck liver by direct injection of calcium phosphate-precipitated DNA. Our aim was to develop a new method of liver-specific gene expression after intravenous DNA delivery. METHODS/RESULTS: We inoculated duck hepatitis B virus DNA with and without cationic liposomes, Lipofectin or LipofectAMINE, as DNA carries. Two weeks after a single intravenous injection of 10 or 50 micrograms of plasmid DNA containing a head-to-tail dimer of duck hepatitis B virus DNA into 25 one-day old ducklings, duck hepatitis B virus RNA transcripts including the pregenome replicative intermediate were detected by Northern blot in the liver of eight ducks (100%) of the Lipofectin group, five ducks (63%) of the LipofectAMINE group, and three ducks (50%) of the group which received DNA without carrier. Duck hepatitis B virus RNA transcription was almost exclusively liver specific, even though the liposomes had no tissue specificity. Replicative forms of duck hepatitis B virus DNA were detected in the liver and DHBsAg was observed in the cytoplasm of the hepatocytes by immunostaining. The serum of transfected ducklings contained virus particles which were infectious in other ducklings. CONCLUSION: The efficient and liver-specific expression of inoculated DNA was due to the amplification of nucleic acids by active virus replication process under the control of hepatocyte specific regulation.

Animals↗

PubMed1996

Inhibitory effect of magnesium L-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo.

BACKGROUND: An inhibitory effect of ascorbic acid (AsA) on melanogenesis has been described. However, AsA is quickly oxidized and decomposed in aqueous solution and thus is not generally useful as a depigmenting agent. OBJECTIVE: Our purpose was to examine the effect on pigmentation of magnesium-L-ascorbyl-2-phosphate (VC-PMG), a stable derivative of AsA. METHODS: Percutaneous absorption of VC-PMG was examined in dermatomed human skin, and its effect on melanin production by mammalian tyrosinase and human melanoma cells in culture was also measured. A 10% VC-PMG cream was applied to the patients. RESULTS: VC-PMG suppressed melanin formation by tyrosinase and melanoma cells. In situ experiments demonstrated that VC-PMG cream was absorbed into the epidermis and that 1.6% remained 48 hours after application. The lightening effect was significant in 19 of 34 patients with chloasma or senile freckles and in 3 of 25 patients with normal skin. CONCLUSION: VC-PMG is effective in reducing skin hyperpigmentation in some patients.

Ascorbic Acid↗

PubMed1996

Analysis of a germ line polymorphism of the p53 gene in lung cancer patients; discrete results with smoking history.

The p53 tumor suppressor gene is often mutated in various human cancers and a common polymorphism is known at codon 72 of exon 4, with two alleles encoding either arginine (CGC) or proline (CCC). Association of this polymorphism with any human cancer susceptibility has yet to be clarified. We have conducted a case-control study in Japan on the distribution of the three genotypes with 191 lung cancer patients, 152 control patients with non-cancerous pulmonary diseases and 115 colorectal cancer patients. The genotypes were examined by PCR using DNA samples from peripheral blood lymphocytes. Frequency distributions of the three genotypes were quite comparable with each other among groups, with allelic frequencies of approximately 60% for arginine and 40% for proline. The genotypic frequencies in lung cancer patients, however, were largely different between smokers and non-smokers (chi 2 = 13.5, df = 2, P < 0.001). Compared with the control and colorectal cancer patients a significant difference in genotypic frequency was observed only in non-smoker lung cancers (chi 2 = 10.9, df = 2, P < 0.01), with an excess of Arg/Arg homozygotes and a deficit of Arg/Pro heterozygotes. Our present data suggest that the p53 polymorphism affects the risk of lung cancer unrelated to smoking.

Arginine↗

PubMed1996

Immunolocalization of glutathione-peroxidase (GSH-PO) in the rat ventral prostate: effects of castration and administration of testosterone.

Immunolocalization of glutathione-peroxidase (GSH-PO) in the rat ventral prostate was studied in the presence and absence of androgen. Male Sprague-Dawley rats were divided into four experimental groups. Group 1 consisted of intact controls. In group 2, rats were sacrificed two days after castration. In groups 3 and 4, rats were injected subcutaneously with 1 mg of testosterone-propionate daily, for three or seven days, beginning two days after castration. The intensity of GSH-PO staining in the glandular epithelial cells of the ventral prostate decreased after castration, but recovered following treatment with testosterone. Furthermore, the prostatic GSH-PO mRNA levels were diminished in the castrated rat ventral prostate but greatly increased by testosterone. These findings strongly suggest that the expression of GSH-PO in the glandular epithelial cells of the rat ventral prostate is dependent on testosterone.

Animals↗

PubMed1995

Elevation of alkaline phosphatase activity induced by parathyroid hormone in osteoblast-like cells from the spinal hyperostotic mouse TWY (twy/twy).

We have examined the alkaline phosphatase (AP) activity of primary calvaria-derived osteoblast-like cells from the twy (tip-toe walking Yoshimura) and normal ICR control mouse. The twy mouse displays elevated osseous formation particularly in the spine, and the pathophysiological features resemble that of human ankylosing spinal hyperostosis. In the proliferative stage of cultured bone cells, parathyroid hormone (PTH) stimulation induced the elevation of AP activity of both twy and ICR mouse-derived cells. When they reached confluence, the AP activity of ICR mouse-derived cells ceased to increase with PTH stimulation. The twy mouse-derived cells, however, continued to respond to PTH, with the enzyme activity increasing even in the confluent, stationary stage. PTH stimulation also increased the intracellular cAMP content of twy mouse-derived cells but it did not influence that of ICR mouse-derived cells in the stationary stage. Moreover, stimulation with dibutyryl cAMP, but not with phorbol myristate acetate, increased the AP activity of both twy and ICR-derived bone cells irrespective of culture conditions, either in the proliferative or in the confluent stage. These data suggest that the protein kinase A-mediated pathway plays a pivotal role in bone cells with PTH stimulation, and that the uninhibited AP activity observed in twy mouse-derived bone cells might be due to some deviating process between the PTH ligand/receptor interaction and cAMP generation.

Alkaline Phosphatase↗

PubMed1995

Stimulation of endosteal bone formation by systemic injections of recombinant basic fibroblast growth factor in rats.

In vivo effects of basic fibroblast growth factor (bFGF) on bone formation was examined in rats. Daily systemic injections of 100 micrograms/kg bFGF for 7 days caused a marked stimulation of endosteal bone formation in both cortical and secondary cancellous bone areas. Histological examinations revealed that the sequence of responses to the injections of bFGF consisted of three phases: an early increase in the number of preosteoblastic cells over the osteoblastic cell layer (days 1-3), recruitment of osteoblasts from preosteoblastic cells (days 3-5), and an increase in new bone formation (days 5-7). These histological changes in the endosteum correlated closely with histomorphometrical parameters of bone formation, and the endosteal mineral apposition rate was almost unaffected during the initial 4 days but was markedly enhanced after this period. Immunohistochemical examinations using antitransforming growth factor (TGF)-beta 1 antibody demonstrated that immunostaining of preosteoblastic cells for TGF-beta already increased 1 day after bFGF treatment. Distribution of TGF-beta in osteoblasts and bone matrices began to increase on day 3, and all the osteoblasts and new bone matrices were intensively immuno-stained on day 7. These results demonstrate that systemic injections of bFGF in rats stimulate endosteal bone formation, and that the stimulation of bone formation is preceded by an initial increase in preosteoblastic cells with later recruitment of osteoblasts from these cells. Because the distribution of TGF-beta in the endosteal cells is increased by bFGF, the effect of bFGF may at least in part be mediated by TGF-beta. However, the precise mechanism of action of bFGF on bone formation remains to be clarified.

Animals↗

PubMed1995

Regression of hypertrophic osteopathy following removal of intrathoracic neoplasia derived from vagus nerve in a dog.

Surgical removal of an intrathoracic tumor derived from a vagus nerve was undergone in a dog with hypertrophic osteopathy. The tumor was pathologically diagnosed as malignant schwanoma. Soft tissue swelling, lameness, and itchiness in four limbs disappeared within 7 days after surgery. The proliferated periosteal osteophytes of the four limbs was progressively reduced with time by follow-up radiography on the 58th day after surgery. On the 710th day after surgery, these osteophytes were greatly decreased as osteopathy, malignant schwanoma.

Animals↗

PubMed1995

Effect of TCV-309, a novel platelet activating factor antagonist, on hemodynamics in dogs with endotoxin-induced shock.

The therapeutic effects of TCV-309, a novel platelet activating factor antagonist, on hemodynamics in endotoxin-induced shock were evaluated. Ten Beagle dogs were used under general anesthesia and artificial ventilation. After intravenous injection of endotoxin (3 mg/kg), TCV-309 (1 mg/kg) was administered intravenously to the dogs. The results showed that the depression of mean aortic pressure, cardiac output, left ventricular stroke work index and urine volume which occurred in endotoxin shock was significantly improved by administration of TCV-309. These results suggested that TCV-309 was a useful therapeutic for the circulatory disturbance in endotoxin shock.

Animals↗

PubMed1995

Effect of platelet activating factor antagonist (TCV-309) on lung injury in dogs with experimentally endotoxin-induced shock.

The effect of TCV-309, a newly developed platelet activating factor (PAF) antagonist, on the wet/dry weight ratio of the lung (index of pulmonary edema) and the pulmonary surface activity (index of pulmonary compliance) was evaluated in comparison with that of CV-3988 (PAF-antagonist). Administration of TCV-309 (1 mg/kg) or CV-3988 (10 mg/kg) significantly reduced the wet/dry weight ratio which was increased by endotoxin administration (3 mg/kg). It also augmented the pulmonary surface activity. Administration of either TCV-309 or CV-3988 alleviated the histologic lesions caused by endotoxic shock. These results suggest that lung injury during endotoxic shock can be controlled by TCV-309 as by CV-3988.

Animals↗

PubMed1995

Effect of platelet activating factor antagonist (CV-3988) on 6-keto-PGF1 alpha and thromboxane B2 in dogs with experimental endotoxin-induced shock.

The effect of CV-3988, a platelet activating factor antagonist, in the treatment of endotoxic shock was evaluated from the changes in plasma 6-keto-PGF1 alpha and thromboxane B2 concentrations. The animals consisted of 10 beagle dogs anesthetized with pentobarbital sodium and divided into a treatment group (n = 5) and a control group (n = 5). Endotoxic shock was experimentally induced in both groups by intravenous administration of endotoxin (lipopolysaccharide, 3 mg/kg). The treatment group was intravenously given 10 mg/kg of CV-3988 for 10 min from immediately after endotoxin. Mean aortic pressure, cardiac output and urine volume were remarkably decreased after the administration of endotoxin to both groups. These parameters were higher after the administration of CV-3988, in the treatment group than in the control group. Furthermore, the increase in plasma 6-keto-PGF1 alpha and thromboxane B2 concentrations was significantly inhibited. These results suggest the effectiveness of CV-3988 in the treatment of endotoxic shock.

6-Ketoprostaglandin F1 alpha↗