Biomedical subjects

M Tagawa

Publications and source records attributed to M Tagawa.

At least 73 records · Page 4Linked to original sources

PubMed2000

[Chromosome 1 abnormalities at band 1p32 in two atomic bomb survivors with myelodysplastic syndrome].

We reported on 2 atomic bomb survivors(a 60-year-old man and 63-year-old woman)suffering myelodysplastic syndrome(MDS) associated with 1p32 chromosomal abnormalities. They were exposed to atomic bomb radiation at distances of 1.2 and 1.1 km, respectively, and were given a diagnosis of MDS 44 and 46 years after the bombing, respectively. The male patient had refractory anemia(RA) and a bone marrow cell karyotype of 46, XY, del(1)(p22p32), t(8;11)(p11;p15). The female patient had RA with excess of blasts (RAEB) and a karyotype of 45, X, -X, t(1;11)(p32;q23), +del(1)(p32), inv(3) (p21q27), del(5)(q15), -6, -9, -19, +mar 1, +mar 2. Multi-separated nuclear megakaryocytes were observed in both patients. These findings suggested that they had been exposed to radiation near the atomic explosion despite the fact that their symptoms of MDS developed more than 40 years after the bombing. 1p32 is known to be the locus of the TAL1 gene. However, Southern blot analysis did not reveal rearrangement of the TAL1 gene in the male patient.

Chromosome Aberrations↗

PubMed2000

Histopathological studies of subcutaneous implantation of chlormadinone acetate (CMA) for preventing estrus in queens.

The efficacy and clinical safety of chlormadinone acetate (CMA) in preventing estrus were assessed in queens on condition that CMA was subcutaneously implanted in siliastic rubber. Thirteen queens were divided into the following four groups according to dose of CMA-administered: group 1 (n = 3), control; group 2 (n = 3), 2.5 mg/kg; group 3 (n = 3), 5 mg/kg; group 4 (n = 4), 20 mg/kg. The implants were left in these queens for 12 months after implantation. All control animals showed signs of estrus during the experiment, with periods of anestrus of normal duration. In contrast, estrus was completely inhibited in the CMA-treated groups. Histopathologically, the uterus from group 4 had coiled branched glands with little secretion in the endometrium. Mammary glands from the CMA-treated groups showed mild lobular development with acinar proliferation and secretion. Sections through the other organs (pituitary gland, adrenal gland, ovary, and implant site) had no distinct or consistent changes that could be related to the CMA-treated. It was concluded, therefore, subcutaneous implantation of CMA could be the good drug-delivery system for reducing changes due to the antigonadotropic and glucocorticoid-like activities and serious condition in the uterine and mammary gland due to progestagenic activity.

Animals↗

PubMed2000

Effect of antiandrogen, chlormadinone acetate (CMA), in canine spontaneous benign prostatic hyperplasia (BPH).

The effect of synthetic steroidal antiandrogen, chlormadinone acetate (CMA), on spontaneous benign prostatic hyperplasia (BPH) in dogs was investigated. Male beagle dogs (5-8 years old) were divided into three experimental groups. Group 1 consisted of untreated controls. Groups 2 and 3 received CMA 0.03, and 0.1 mg/kg/day, p.o., respectively, for 6 months. In group 1, glandular hyperplasia of the prostate was clearly detected. In groups 2 and 3, CMA produced marked atrophy of the glandular epithelium. In addition, a histopathological study showed that CMA medication for 6 months exerted no effect on the testes and adrenals or on immunoreactive LH- and ACTH- cells of the anterior pituitary glands. Therefore, it is suggested that CMA (0.03 and 0.1 mg/kg) causes regression of spontaneous canine BPH without any histopathological effects on the testes, adrenals or anterior pituitary LH- and ACTH-cells.

Adrenal Glands↗

PubMed2000

[The role of positron emission tomography in neuropharmacology in the living human brain and drug development].

Neuroimaging is a powerful and innovative tool for studying the pathology of psychiatric and neurological diseases and, more recently, for studying the drugs used in their treatment. Technological advances in imaging have made it possible to noninvasively extract information from the human brain regarding a drug's mechanism and site of action. Until now, our understanding of human brain pharmacology has depended primarily on indirect assessments or models derived from animal studies. However, the advent of multiple techniques for human brain imaging allows researchers to focus directly on human pharmacology and brain function. In this review article, our PET studies on histaminergic neuron system were presented as an example. We have developed and used the PET techniques for 10 years in order to examine the functions of histaminergic neurons in the living human brain. This review outlines available PET techniques and examines how these various methods have already been applied to the drug development process and neuropharmacology in the living human brain.

Brain↗

PubMed2000

[Changes of vascular reactivity following esophagectomy measured by near-infrared spectroscopy].

We examined the alterations of peripheral vascular responses following ischemic insult during perioperative period of esophagectomy. Increase of palm blood flow after vascular occlusion, i.e., reactive hyperemia (RH), measured by near-infrared spectroscopy (NIRS) was employed to assess forearm vascular responses. The measurements of RH were performed in esophagectomized patients (n = 12) before induction of anesthesia and postoperatively until the next day of extubation in comparison with normal volunteers (n = 11). After esophagectomy, the RH, which was comparable with those in volunteers, was depressed by 50% on 1 POD, and did not recover until the third POD. In particular, patients receiving laparoscopy-assisted surgery showed less decrease of RH than those receiving the standard open laparotomy. These results suggest that vascular responses to increase blood flow against ischemic insult is depressed following esophagectomy.

Adult↗

PubMed2000

Histopathological study of female beagle dogs for four year treatment with subcutaneous implantation of chlormadinone acetate (CMA).

The histopathological changes related to chlormadinone acetate (CMA) implantation were examined using female beagle dogs given 10mg/kg for four years. All control animals showed sign of estrus during the experiment, with periods of anestrus of normal duration. In contrast, estrus was completely inhibited in the CMA-implanted animals. Histopathologically, uterine sections from the CMA-implanted animals showed cystic glandular hyperplasia, but no histologic evidence of endometritis, myometritis, and pyometra was found. In the ovaries of the CMA-implanted animals, developing ovarian follicles were observed but no mature follicles were noted in addition to an absence of corpus luteum. No remarkable changes were observed in the liver, adrenal, mammary gland, gallbladder and implanted site. Furthermore, the intensity of staining and number and size of ACTH-and LH-positive cells in the pituitary sections of CMA-implanted animals were not different from control animals. It was concluded, therefore, that subcutaneous implantation of CMA is a potential drug-delivery system for reducing changes due to antigonadotropic and glucocorticoid-like activities and characteristic histopathological changes in the uterus due to progestagenic activity.

Animals↗

PubMed1999

Acquired immunity in nude mice induced by expression of the IL-2 or IL-4 gene in human pancreatic carcinoma cells and anti-tumor effect generated by in vivo gene transfer using retrovirus.

We have examined the anti-tumor effect in nude mice caused by human pancreatic cancer cells (AsPC-1) modified to secrete IL-2 or IL-4. Loss of tumorigenicity of cytokine-producing, but not wild-type, cells was observed despite their unaltered in vitro proliferation rates; and these anti-tumor effects were dependent on the amount of cytokine released. Wild-type cells inoculated into mice which had rejected IL-2- or IL-4-producer cells showed significant growth retardation, while no retardation was detected when unrelated human colon carcinoma cells were inoculated. Histological examination of regressing IL-2- or IL-4-producing AsPC-1 tumors in nude mice revealed infiltration by CD11b-, but not CD90-, positive cells around the tumors. Treatment of nude mice with anti-asialoGM(1) antibody did not affect loss of tumorigenicity. Mice injected i.p. with IL-2- or IL-4-producing AsPC-1 cells did not die, in contrast to mice inoculated with wild-type cells. Injection of retrovirus-bearing IL-2, but not beta-galactosidase, gene into mice which had wild-type cells in the peritoneal cavity also significantly prolonged survival. Thus, expression of the IL-2 or IL-4 gene in AsPC-1 cells may generate tumor-specific acquired immunity, even in mature T cell-deficient conditions. An anti-tumor response can be induced by in vivo transfer of the IL-2 gene.

Animals↗

PubMed1999

Exon 9 mutations in the WT1 gene, without influencing KTS splice isoforms, are also responsible for Frasier syndrome.

We report new mutations in exon 9 of the WT1 gene that did not alter the ratio of +/- KTS splice isoforms in two unrelated patients with Frasier syndrome (FS). The mutation of intron 9 inducing defective alternative splicing was reported to be responsible for this syndrome. The mutations found in our cases occurred in the same exon of the WT1 gene as detected in Denys-Drash syndrome (DDS) and could not be explained by the previously proposed mechanism. The results suggest that the two syndromes originate from the same WT1 gene abnormality. From a molecular biological point of view, we concluded that the two diseases were not separable, and that FS should be included as an atypical form of DDS.

Adult↗

PubMed1999

Spontaneous negativation of serum hepatitis C virus RNA is a rare event in type C chronic liver diseases: analysis of HCV RNA in 320 patients who were followed for more than 3 years.

BACKGROUND/AIMS: The natural course of hepatitis C virus (HCV) replication in type C liver diseases has not yet been elucidated. The aim of the study was to investigate the spontaneous outcome of the viremia by examining the changes in HCV RNA in patients with chronic type C liver diseases. METHODS: Among patients who visited our liver clinic between June 1981 and December 1993, 320 patients with chronic type C liver diseases were followed for at least 3 years and had no history of interferon treatment. HCV RNA was examined by a highly specific reverse transcription-polymerase chain reaction method in paired serum samples obtained from these patients at the beginning and end of follow-up. RESULTS: Among the 320 cases, HCV RNA was seropositive in 310 (97%) cases at the beginning of follow-up. Of these 310, HCV RNA remained seropositive in 304 (98%) and became seronegative in six (2%) cases by the end of follow-up. All of these six patients had liver cancer. HCV RNA became seronegative after the patients entered the state of liver failure because of the development of tumors or portal thrombosis. The remaining 10 cases who were seronegative for HCV RNA at the beginning were seropositive at the end of follow-up. Among the 320 cases, serum alanine aminotransferase normalized and remained normal for more than 12 months until the end of follow-up in 11 cases (0.6%/year/case), but none became negative for HCV RNA. CONCLUSIONS: Thus, during the natural course of chronic HCV infection, spontaneous negativation of serum HCV RNA seems extremely rare, at least in patients with chronic active hepatitis or cirrhosis of the liver, and may occur primarily at the terminal stage when tumors cause liver failure.

Aged↗

PubMed1999

Resistance to apoptosis induced by microenvironmental stresses is correlated with metastatic potential in Lewis lung carcinoma.

The apoptosis-resistant phenotype of cloned high-metastatic A11 and low-metastatic P29 cells isolated from Lewis lung carcinoma was compared. The results showed that A11 cells were more resistant to apoptosis induced by microenvironmental stresses such as serum starvation, glucose deprivation and hypoxia than P29 cells as judged by viability, DNA laddering, and chromatin condensation and fragmentation. Both cell lines were insensitive to tumor necrosis factor-alpha-mediated apoptosis. P29 cells expressed a much higher level of Fas antigen on the cell surface than A11 cells. However, both cell lines were also insensitive to Fas-mediated apoptosis. The apoptosis resistant phenotype of A11 cells was associated with the expression level of caspase-3, but not with those of Bcl-2, Bcl-X(L) Bax, p27Kip1 and DAP kinase. There was no difference between A11 and P29 cells in the expression of E-cadherin, the adhesiveness to the extracellular matrix components or the expression levels of metastasis-associated genes such as c-Ha-ras, c-jun, p53 and nm23. Furthermore, A11 cells exhibited lower motile and invasive abilities than P29 cells. These results suggest that the apoptosis-resistant phenotype is an important factor for determining the metastatic ability of A11 cells. Supporting this, P29 cells became more apoptosis-resistant after treatment of the cells with dimethylsulfoxide which is reported to enhance the experimental metastatic potential of the cells.

Animals↗

PubMed1999

Frequent expression of midkine gene in esophageal cancer suggests a potential usage of its promoter for suicide gene therapy.

We have examined the expression of midkine (MK), a neurotrophic factor with heparin-binding activity, in human esophageal cancer cells. Seven esophageal cell lines tested expressed the transcript and 8 out of 14 human esophageal tumor specimens were positively stained with anti-MK antibody, while surrounding normal esophageal tissues in these specimens were not stained. The 5'-flanking, 2.3 kb genomic region of the MK gene was shown to drive the transcription of a reporter gene in the esophageal cell lines in a cis acting manner. Forced expression in esophageal cancer cells of herpes simplex virus-thymidine kinase gene mediated by the flanking region of the MK gene conferred sensitivity to a prodrug, ganciclovir. The 5'-upstream region of the MK gene thus possesses putative promoter activity which can be used for suicide gene-based gene therapy for esophageal cancer.

Aged↗

PubMed1999

Genotype difference of aldehyde dehydrogenase 2 gene in alcohol drinkers influences the incidence of Japanese colorectal cancer patients.

A case-control study was conducted to explore the possible etiologic role of alcohol and aldehyde dehydrogenase 2 (ALDH2) gene among Japanese colorectal cancer patients. Information on their drinking, smoking and dietary habits was collected from 265 colon and 164 rectum cancer patients, and 794 non-cancer patients as a control group. Genotypes of the ALDH2 gene at codon 487, glutamic acid (ALDH2*1) as a wild-type or lysine (ALDH2*2) as a mutated type with reduced enzyme activity, were analyzed by polymerase chain reaction in 160 colon and 110 rectum cancer patients and 121 control persons. Univariate analysis with the chi 2 statistical test showed that heavy alcohol drinking (P < 0.01), frequent meat intake (P < 0.001), and irregular (P < 0.01), hasty (P < 0.01) and excessive (P < 0.001) eating habits were associated with the incidence of both colon and rectum cancers, whereas heavier smoking (P < 0.05) and infrequent fish (P < 0.03) and fruit (P < 0.01) intake were solely associated with incidence of rectum cancer. Infrequent green vegetable intake was not correlated with the incidence of colorectal cancer. Multivariate unconditional logistic regression analysis confirmed the association of alcohol consumption (P < 0.01) and meat intake (P < 0.05). Homozygous and heterozygous carriers of ALDH2*2 allele tended to be found in colon (trend P = 0.04) but not in rectum cancer patients compared to controls. Risk elevation for colon cancer due to alcohol consumption was pronounced among the heterozygotes and it was statistically significant especially for distal colon cancer (trend P = 0.02). We conclude that alcohol consumption is a risk factor for colorectal cancer and the risk can be enhanced in ALDH2 heterozygotes.

Adult↗

PubMed1999

Ventricular fibrillation with small amplitude of activation and its implications for implantable cardioverter defibrillator treatment.

An implantable cardioverter defibrillator (ICD) was implanted in a patient with ventricular fibrillation (VF) related to old myocardial infarction. During VF, amplitude of ventricular activation was small, and the ventricular sensitivity at 1.2 mV failed to detect several small ventricular activations. When the sensitivity was changed to 0.3 mV, both under- and oversensed beats occurred during VF, and at the ventricular sensitivity of 0.15 mV, the undersensed beats disappeared while oversensed beats markedly increased. Defibrillation test was repeated one and four weeks after the implantation, and these inappropriate beats were minimized at the ventricular sensitivity of 0.3 mV. We should pay attention to the amplitude of ventricular activation to avoid possible trouble in ICD therapy.

Aged↗

PubMed1999

A significant relationship between glutathione-peroxidase (GSH-PO) localization and biological action of testosterone in rat ventral prostate.

In order to confirm the relationship between glutathione-peroxidase (GSH-PO) localization and biological testosterone action in the rat ventral prostate, immunocytochemical localization of GSH-PO in glandular epithelial cells of the rat ventral prostate was investigated. In the untreated group, GSH-PO was predominantly demonstrated in glandular epithelial cells of the ventral prostate. Intracellular localization of GSH-PO in the glandular epithelial cells was mainly observed in cytoplasmic matrix near the rough endoplasmic reticulum and was occasionally noted as a small granular structure (GSH-PO-positive granule) at the supranuclear region. In a castrated animal, the intensity of GSH-PO staining in the glandular epithelial cells was remarkably decreased. By testosterone administration to the castrated animal, GSH-PO was clearly detected in the glandular epithelial cells. Intracellular localization of GSH-PO was mainly observed in cytoplasmic matrix and the number of GSH-PO-positive granules increased remarkably. These findings suggest that immunostainable GSH-PO in the glandular epithelial cells of the rat ventral prostate is testosterone-dependent, and that its staining pattern is a useful marker for biological testosterone action.

Animals↗

PubMed1999

Regulation of prostatic glutathione-peroxidase (GSH-PO) in rats treated with a combination of testosterone and 17 beta-estradiol.

In order to confirm the relationship between sex hormone administration and glutathione-peroxidase (GSH-PO) in the rat ventral prostate, the levels of GSH-PO mRNA, GSH-PO activity, and lipid peroxide (TBA) value in the ventral prostate were investigated. Male Crj:CD(SD)IGS rats were divided into six 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 subcutaneously administered 1 mg/animal of testosterone daily for three or seven days after two days of castration, respectively. In groups 5 and 6, rats were subcutaneously administered 1 mg/animal of testosterone plus 0.01 mg/animal of 17 beta-estradiol (E2) daily for three or seven days after two days of castration, respectively. GSH-PO activity of the ventral prostate homogenate for testosterone or testosterone plus E2 administration to the castrated rat was increased and the TBA value was remarkably decreased. The prostatic GSH-PO mRNA level was diminished in the castrated rat ventral prostate, but was increased by testosterone or testosterone plus E2 administration. In particular, the GSH-PO mRNA level of testosterone plus E2-treated animals was higher than that of testosterone-treated animals. These findings strongly suggest that expression of GSH-PO in the rat ventral prostate is considered to be testosterone- or E2-dependent. Furthermore, it is suggested that the transcription of prostatic GSH-PO mRNA was regulated by testosterone or E2 and de novo synthesis of GSH-PO would thus be regulated at transcription level by testosterone or E2.

Animals↗

PubMed1999

Expression of wild-type p53 gene confers increased sensitivity to radiation and chemotherapeutic agents in human esophageal carcinoma cells.

The status of the p53 gene of tumor cells can modify the sensitivity of the tumors to radiation and anti-cancer agents. Human esophageal cancer cells (T.Tn) bearing mutated p53 gene were retrovirally transduced with wild-type p53 gene. The transduced cells (T.Tn/p53) which stably expressed wild-type p53 proliferated at the same rate as parental cells. However, the sensitivity to radiation was significantly improved by the transduction and T.Tn/p53 cells became markedly susceptible to cisplatin and etoposide compared with parental cells. Administration of cisplatin noticeably suppressed the growth of T.Tn/p53 tumors but not T.Tn tumors inoculated in nude mice. Forced expression of wild-type p53 gene thereby can increase the sensitivity to DNA damage in esophageal cells.

Animals↗

PubMed1999

Loss of tumorigenicity of human breast cancer cells engineered to produce IL-2, IL-4 or GM-CSF in nude mice.

Human breast cancer cells (OCUB-M), retrovirally transduced with granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin-2 (IL-2) or IL-4 gene were examined for their antitumor activities in nude mice. Although cell proliferation rates in vitro of these cytokine-producing cells were not significantly different from that of wild-type cells, nude mice that were subcutaneously inoculated with cytokine-producing cells did not develop tumors in contrast to mice that were injected with wild-type cells. Injection of GM-CSF-producing cells into the vicinity of growing wild-type tumors retarded subsequent growth of wild-type tumors. Histological examination of tumors which received GM-CSF-producing cells revealed marked infiltration of mononuclear cells around the tumors. Irradiation of cytokine-producing cells diminished their proliferation capacity but production of cytokine(s) was retained. Therefore, inoculation of irradiated cytokine producer cells into growing tumors can be used as a therapeutic maneuver for breast cancer.

Animals↗

PubMed1999

Homozygous deletion of the p16/MTS-1/CDKN2 gene in malignant gliomas is infrequent among Japanese patients.

We have analyzed the status of the p16/MST-1/CDKN2 gene in 63 brain tumors from Japanese patients. With quantitative multiplex polymerase chain reaction (PCR) assay using the exon 2 primers of the p16 gene and control chromosome 9qSTS primers, we found homozygous deletion of the p16 gene in 7 cases; in 1 out of 10 cases of anaplastic astrocytomas (WHO grade III), 6 out of 35 cases of glioblastoma multiformes (grade IV) but in none of the tumors of grade I or II. We also found mobility-shifted PCR products in 8 cases using the single-strand conformation polymorphism technique. DNA sequencing of the aberrantly migrated products revealed that 5 cases of glioblastoma multiforme had mutations which caused amino acid substitutions. We found one case with silent mutations and two cases with nucleotide changes in the non-coding region. The frequency of the alteration of the p16 gene, either homozygous deletion or mutation accompanied with amino acid substitutions, increased in malignant brain tumors (grade III and IV) compared with that in low grade tumors (grade I and II) (p=0.0275), suggesting possible role(s) of the gene in the progression of brain tumors. In addition, the low frequency of homozygous deletions shown in this study is quite different from previous reports that demonstrated frequently deleted p16 gene in malignant gliomas from Caucasian patients. We have also shown the presence of heterogeneous cell populations within the glioblastoma masses based on the variety of the mutated p16 sequences. The present study, therefore, suggests a possible racial difference in the mechanism of the tumorigenesis and a heterogeneity of malignant gliomas developed during the tumor progression.

Adolescent↗