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Biomedical subjects

M Izawa

Publications and source records attributed to M Izawa.

At least 91 records · Page 5Linked to original sources

Helminths of the Tsushima leopard cat (Felis bengalensis euptilura).

Three Tsushima leopard cats (Felis bengalensis euptilura) in Japan were collected as road kills. Three species of trematodes (Pharyngostomum cordatum, Paragonimus sp. and Dicrocoeliidae gn. sp.), one species of cestode (Spirometra erinacei) and nine species of nematodes (Arthrostoma hunanensis, Uncinaria felidis, Uncinaria sp., Ancylostoma tubaeforme, Molineus springsmithi, Toxocara cati, Capillaria aerophila, Capillaria felis-cati, and Capillaria sp.) were found. Among these helminths, Arthrostoma hunanensis, Uncinaria spp., and Molineus springsmithi have not been reported previously in Japanese domestic cats.

Animals↗

Inhibition of chemical carcinogenesis in vivo by azatyrosine.

A single painting of 7,12-dimethylbenz[a]anthracene on the skin of transgenic mice harboring the human protooncogene c-Ha-ras induced papillomas at 100% incidence after 20 weeks (M. Izawa et al., unpublished data). Application of L-beta-(5-hydroxy-2-pyridyl)alanine (azatyrosine) to the skin at a dose of 2 mg/mouse once every 3 days after initiation with 7,12-dimethylbenz[a]anthracene greatly reduced the percentage incidence, number per mouse, and size of papillomas. Injection of methylnitrosourea i.p. into transgenic mice induced papillomas in the forestomach after 12 weeks (2 to 12 papillomas/mouse) at 100% incidence (K. Ando et al., Cancer Res., 52: 978-982, 1992). Administration of azatyrosine i.p. at a dose of 2 mg/mouse once every 2 days for 12 weeks after initiation with methylnitrosourea completely prevented the formation of forestomach papillomas. These results clearly indicated that azatyrosine inhibits chemical carcinogenesis in vivo.

9,10-Dimethyl-1,2-benzanthracene↗

Aspergillotic aneurysm formation of cerebral artery following neurosurgical operation.

A rare case of intracranial aspergillotic aneurysm following neurosurgical operation for facial spasm is presented. Severe meningitis had persisted several days prior to the subarachnoid hemorrhage which occurred on 70th postoperative day. Angiography demonstrated a fusiform aneurysm at the peduncular segment of the superior cerebellar artery on the other side of operation. As the repeated cultures of CSF were negative, the pathogenetic factor causing aneurysm formation could not be identified before second operation of aneurysmal resection. Pathological study of the specimen revealed the arterial wall being deeply invaded by aspergillotic hyphae.

Adult↗

Detection of xenogeneic anti-idiotypic antibodies specific to murine monoclonal antibody 17-1A in patients with gastrointestinal cancer.

Murine monoclonal antibody (MoAb) 17-1A, which reacts with an adenocarcinoma-associated antigen, has recently been utilized in a phase I clinical trial for patients with gastrointestinal tract cancers in Japan. In order to analyze anti-idiotypic (Id) antibodies to murine MoAb 17-1A in the sera of these cancer patients, we established a simple and specific assay. In a modified sandwich assay, normal mouse sera were utilized for neutralization of rat antimouse immunoglobulin (Ig) antibodies and reduction of their nonspecific effects. When the modified sandwich assay was applied to the sera of patients who had been treated with MoAb 17-1A, anti-Id antibodies were induced in 53% of 13 cancer patients with gastrointestinal cancers at 3-4 weeks after infusion of MoAb.

Animals↗

A case of amylase-producing lung cancer.

A case of lung cancer with hyperamylasemia was studied. Small cell carcinoma was diagnosed histologically. The salivary gland and pancreas had no clinical involvement in the hyperamylasemia. Saliva-type amylase was dominant as observed from amylase isozyme patterns in the serum and tumorous tissue. Levels of amylase were higher in tumorous tissue than in normal lung tissue. Immunohistochemical study showed amylase localized in tumor cells. Observation of the ultrastructure revealed electron-dense granules in the cytoplasm of the tumor cells. Findings suggested that amylase was being produced by the lung cancer in this case.

Amylases↗

Risk factors for brain abscess in patients with congenital cyanotic heart disease.

Brain abscess is a serious complication of congenital cyanotic heart disease. We retrospectively evaluated the risk factors for brain abscess in 21 such patients treated between 1975 and 1990 in comparison with a control group. The mean arterial oxygen saturation, arterial partial pressure of O2, arterial blood oxygen content, and base excess in patients with brain abscess were significantly lower than in the control patients. The mean arterial partial pressure of CO2, pH, hematocrit, hemoglobin, and red blood cell content in patients with brain abscess were not significantly different. Patients with congenital cyanotic heart disease may develop minute encephalomalacia due to severe hypoxemia and increased blood viscosity resulting from compensatory polycythemia. The increased blood viscosity and reduced blood flow in the microcirculation may induce cerebral thrombosis or exaggerate minute encephalomalacia during dehydration or cardiac dysfunction, and shunted blood containing infectious organisms at such sites may be followed by focal cerebritis.

Brain Abscess↗

Tissue distribution of recombinant mouse interferon-gamma and recombinant human interferon-gamma in mice, rats, hamsters, and monkeys.

Homologous (mouse) and heterologous (human) recombinant interferon-gamma (IFN-gamma) interferons were injected intravenously into C57BL/6 mice. After 5 min, the greatest proportion of the human IFN was found in the liver, whereas no mouse IFN was detected in the liver at this time or later. Similar results were found in rats, hamsters, and cynomolgus monkeys. Thus, the tissue distribution of these two recombinant IFN-gamma in the various species is not determined by species specificity but by the physicochemical characteristics of the molecules.

Animals↗

Nucleotide sequences of cDNA clones, pSv-1 and pSv-2, hybridizing to androgen-stimulated mRNAs in rat seminal vesicles.

In order to further characterize the cDNA clones, pSv-1 and pSv-2, which had been newly isolated from a cDNA library of intact rat seminal vesicles as clones hybridizing to androgen-stimulated mRNAs of approximately 1,500 and 3,500 nucleotides in length, respectively, the whole nucleotide sequences were determined. The pSv-1 and pSv-2 were 1135 and 1819 nucleotides in length, respectively, and seemed not to contain entire sequences corresponding to the mRNAs. When the 0.7 kb HindIII fragments from pSv-1 and the 1 kb fragments from pSv-2 were used to probe rat genomic DNA that had been digested with four restriction enzymes, the Southern blots suggested the existence of multiple genes related to pSv-1 and a single gene related to pSv-2. These results suggest that pSv-1 and pSv-2 provide useful probes not only for further characterization of products encoded by the mRNAs, but also for the study on the physiological roles of androgen-dependent gene expression in rat seminal vesicles.

Androgens↗

Expressions of sulfated glycoprotein 2 and pSvr-1 genes and involution of steroid hormone-dependent rat tissues.

To further survey the molecular mechanisms underlying the involution of steroid hormone-dependent rat tissues, we undertook experiments to test whether or not any significant correlation between the tissue involution and expressions of rat sulfated glycoprotein 2 (SGP-2) and pSvr-1 genes, which had been initially cloned from the Sertoli cells and the seminal vesicles, respectively, and then identified as androgen repressed messages both in the ventral prostate and in the seminal vesicles, could be observed in steroid hormone-dependent rat tissues. Expressions of these genes were stimulated within 48 h after castration of animals both in the ventral prostate and in the seminal vesicles as reported previously, but not significantly altered by ovariectomy in the uterus. Expressions of these genes in the thymus were significantly repressed by the administration of dexamethasone and/or cycloheximide. Although the roles of expressions of SGP-2 and pSvr-1 genes in steroid hormone-dependent tissues remain unclear, their presence might become useful molecular markers of tissue involution not only in androgen-dependent rat tissues but also in glucocorticoid-dependent ones, and also provide excellent model systems for the study of negative regulation mechanism of gene expression by steroid hormones.

Adrenalectomy↗

Clinicopathological study of bacterial intracranial aneurysms.

The authors report the clinicopathological findings in six cases of bacterial intracranial aneurysms. All patients received appropriate high-dose antibiotics, and four were treated surgically. One patient with multiple aneurysms of the main trunks died of disseminated intravascular coagulation. Autopsy disclosed no apparent aneurysm or inflammatory cell infiltration, but a partially interrupted internal elastic lamina and thickened intima were disclosed at the angiographical aneurysm sites. These findings suggest that 1) appropriate high-dose antibiotics are effective against inoperable bacterial aneurysms in the main trunks, 2) new aneurysms may be formed in patients with cyanotic congenital heart disease, because bacterial emboli can directly reach the cerebral circulation and reimplant on the fragile arterial walls after vasculitis. Histological examination of aneurysmal walls revealed inflammatory cell infiltration after resolution of clinical endocarditis. This suggests that both appropriate high-dose antibiotic therapy and surgery should be considered in patients with distal bacterial aneurysms.

Adolescent↗

Chemically induced tumors in transgenic mice carrying prototype human c-Ha-ras genes.

Three independent transgenic mouse lines carrying human prototype c-Ha-ras genes were established. Approximately 50% of the transgenic offspring of these lines developed spontaneous tumors within 18 months. Types of tumors were restricted to angiosarcomas, skin papillomas and lung or Harderian adenocarcinomas. Interestingly, all angiosarcomas (16/16) had point mutations at the 61st codon of the transgenes. Furthermore, they were also very susceptible to the chemical carcinogens, N-methyl-N'-nitrosourea (MNU) and dimethyl-benzanthracene (DMBA). Within 12 weeks after administration of MNU, the transgenic mice developed forestomach papillomas and then carcinomas very frequently, at the rate of almost 100% and almost all of the tumors had point mutations in their transgenes at the 12th codon from GGC (Gly) to GAC (Asp). All the carcinomas of the forestomach, lung and spleen induced by DMBA had point mutations at the 61st codon from CAG (Gln) to CTG (Leu). Because no somatic point mutations in the transgenes have ever been detected in normal tissues of the affected mice, these mutations seemingly activated the human prototype c-Ha-ras transgene. From these results, it is suggested that the somatic mutation of the human c-Ha-ras transgene plays a causative role in the occurrence of natural tumors and those induced by MNU or DMBA administration in transgenic mice. This transgenic mouse provides a unique screening system for chemicals that induce or suppress the tumorigenesis.

Animals↗

[A case of gastric cancer of Borrmann type IV complicated with carcinomatous peritonitis responding well to chemotherapy of tegafur only].

A 46-year-old-male was admitted to our hospital with an unresectable stage of gastric cancer of Borrmann type IV with carcinomatous peritonitis. He was treated only with tegafur 900 mg/day. After 2 months' treatment, computed tomography showed ascites disappeared and a remarkable improvement was observed by barium meal study and endoscopic examination. The patient has survived for 12 months without any abdominal complaints and ascites since the beginning of treatment. Thus, this is a rare case responding well to chemotherapy of tegafur only.

Adenocarcinoma↗

[Clinicopathological studies of three cases of cerebral aneurysms associated with systemic lupus erythematosus].

We report three cases of ruptured cerebral aneurysms associated with systemic lupus erythematosus (SLE). A 52-year-old woman (case 1) with a fifteen-year history of systemic lupus erythematosus suddenly lost consciousness. She was admitted in a state of deep coma. A computed tomography (CT) scan revealed acute hydrocephalus and diffuse subarachnoid hemorrhage in the basal, interhemispheric and bilateral Sylvian cisterns. Fifteen years prior to this admission, cerebral angiograms demonstrated no cerebral aneurysm. She underwent ventricular drainage immediately. Postoperatively, her condition did not improve, and she died on the 18th day. During the autopsy, two saccular cerebral aneurysms were found: one aneurysm was at the right middle cerebral artery bifurcation, and another one was on the anterior communicating artery, which had disruption of the internal elastic lamina and medial smooth muscle, and infiltration of inflammatory cells. In the major cerebral arteries, for example the bilateral internal carotid arteries, disruption or dissection of the internal elastic lamina, intimal fibrosis and transmural infiltration of inflammatory cells were observed. The second patient, a 36-year-old woman with a six-year history of SLE, was admitted to our hospital with sudden severe headache. A CT scan showed subarachnoid hemorrhage, and cerebral angiograms disclosed saccular cerebral aneurysms on the anterior communicating artery and the left superior cerebellar artery, and a fusiform one on the left posterior cerebral artery. Surgery was not recommended because of her multiple medical problems. Her consciousness improved gradually over 2 months. She was transferred to the department of internal medicine for treatment of renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Differentiation-inducing and growth-inhibitory activities of erythroid differentiation factor (EDF/activin A) toward mouse erythroleukemic cells in vivo.

The in vivo differentiation-inducing activity of a purified human erythroid differentiation factor (EDF) toward mouse erythroleukemic cells (MEL cells) was examined. BDF1 mice with diffusion chambers implanted in the peritoneal cavity were treated with continuous i.p. administration of EDF. MEL cells within a diffusion chamber differentiated into hemoglobin-positive cells when treated with EDF, the percentage of the positive cells being 32.3 +/- 28.3 on day 5 as compared to 0.2 +/- 0.3 in the controls. The anti-tumor activity of EDF was also examined in a nude mouse MEL solid tumor model. Daily intra-tumor treatment with EDF for 10 days resulted in 73% suppression of tumor growth on day 25. A histological study revealed that EDF-treated solid tumor cells became hemoglobin-positive, indicating the anti-tumor activity of EDF through induction of differentiation in vivo. EDF could induce in vitro the differentiation of human erythroleukemic cell lines K562 and HEL, as well as the murine cell line. These results indicate the possibility of differentiation therapy for erythroleukemia using EDF.

Activins↗

cDNA cloning of androgen-stimulated mRNAs in rat seminal vesicles: partial characterization of newly isolated cDNA clones, pSv-1 and pSv-2.

As the first step in surveying the molecular mechanism of androgen-responsive gene expression in rat seminal vesicles, the effect of androgen on the mRNAs was examined by in vitro translation assay. When the in vitro translation products of mRNAs from castrated animals (48 h) were compared with those from castrated and testosterone-treated animals (48 h) by SDS-PAGE, several discrete bands which were stimulated or repressed in response to androgen were observed in addition to major peptide bands of SVS IV and SVS V. From these findings, we constructed a partial cDNA library from the seminal vesicle poly(A +)RNAs of androgen-treated rats and screened by differential colony hybridization. Two distinct cDNA clones, pSv-1 and pSv-2, whose mRNAs were differentially stimulated in response to androgen and seemed to be expressed specifically in the seminal vesicles, were isolated. pSv-1 and pSv-2 hybridized to mRNAs of 1,600 and 3,500 nucleotides in length, respectively. These cDNA sequences, newly isolated in the present study, may provide useful probes for the study of molecular mechanism of androgen-responsive gene expression.

Androgens↗

cDNA cloning of androgen-repressed mRNA in rat seminal vesicles: partial characterization of a cDNA clone, pSvr-1.

When the in vitro translation products of mRNAs from castrated animals (48 h) were compared with those from androgen-treated animals (48 h) to survey the molecular mechanism of androgen-responsive gene expressions in the rat seminal vesicles, some peptide bands which were repressed in response to androgen were observed. From these findings, we constructed a partial cDNA library of poly(A+)RNAs which had been isolated from the seminal vesicles of castrated rats (48 h) and modestly enriched with respect to the concentration of androgen-repressed mRNAs by sucrose density gradient centrifugation, and screened by differential colony hybridization. One cDNA clone, pSvr-1, whose mRNA is markedly induced within 24 h after castration of the animal in the seminal vesicles as well as in the ventral prostate, was isolated. pSvr-1 hybridized to a mRNA of 1,700 nucleotides in length. Partial sequence analysis showed that this clone had highly homologous but not identical sequences to those reported for rat sulfated glycoprotein-2. This cDNA clone may provide a useful probe for the study of the negative regulation mechanism of gene expression by androgens.

Androgens↗

Most tumors in transgenic mice with human c-Ha-ras gene contained somatically activated transgenes.

Two independent transgenic mouse lines carrying human hybrid c-Ha-ras genes with their own promoter region encoding prototype products, were established. In these lines, about 50% of transgenic offspring had tumors within 18 months. The tumors developed in restricted tissues and about 60% of affected mice had angiosarcomas. The transgenes were expressed both in the tumors and in all normal tissues. However, somatic mutational activation was detected only in the transgenes of the tumors. The point mutation at the 61st codon, from CAG(Gln) to CTG(Leu), was detected in all angiosarcomas (22/22), some lung adenocarcinomas (3/11) and Harderian gland adenocarcinomas (4/7) in both lines. The other point mutation at the 12th codon from GGC(Gly) to GTC(Val) was detected in two of the four skin papillomas. No mutations on these codons were detected in normal tissues of transgenic mice. Nontransgenic littermates had no tumors at all. From these results, it was strongly suggested that the mouse tumors do not develop only by the expression of the transgenes, and that definite somatic point mutation of the human c-Ha-ras transgenes in certain cell types may be a causative event in tumorigenesis in these transgenic mice.

Animals↗

Embryonal tumors from transgenic mouse zygotes carrying human activated c-Ha-ras genes.

To investigate the function of activated oncogenes we attempted to create transgenic mice carrying activated human c-Ha-ras genes which have their own promoters. However, we never obtained any transgenic pups which developed to term, because all transgenic embryos were malformed, became developmentally arrested conceptuses or developed embryonic tumors during ontogenesis. The mRNA expression of the transgenes was detected in two tumors obtained after introduction of the DNA fragment containing the activated human c-Ha-ras gene for p21 with valine at the 12th codon or with leucine at the 61st codon. Histological analysis indicated that each tumor consisted of at least three types of cells: two originating from different germ layers (the endoderm in one case and the mesoderm in the other) and the third from extra embryonic ectoderm. It was suggested that the activated human c-Ha-ras gene has a critical effect on the development of tumors in normal embryos as well as in transformation of NIH3T3 cells.

Animals↗