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Biomedical subjects

Y Takimoto

Publications and source records attributed to Y Takimoto.

At least 73 records · Page 4Linked to original sources
PubMed1994

An S1 nuclease-sensitive region in the first intron of human platelet-derived growth factor A-chain gene contains a negatively acting cell type-specific regulatory element.

The platelet-derived growth factor (PDGF) A-chain gene is expressed in a tissue- and developmental stage-specific manner. Here we identify an S1 nuclease sensitive region within the first intron that functions as a negative regulatory element in HeLa but not in human glioblastoma (A172) cells in transient transfection assays. A 147 bp DNA fragment that contains this element functions in a position and orientation independent manner to negatively regulate both the PDGF A-chain promoter and the heterologous herpes simplex virus thymidine kinase (TK) promoter. The cell-type specific effect of this 147 bp DNA fragment is seen when it is located downstream but not upstream of the reporter gene driven by either the PDGF A-chain or TK promoters. The negative regulatory element has been localized to a 24 bp DNA sequence within the S1 sensitive site that retains negative regulatory activity and recognizes a nuclear protein in HeLa but not in A172 cells. Furthermore, the 24 bp element functions as a cell type-specific negative element independent of its position. These results suggest that a functional silencer within the first intron exhibits a non-B-form DNA structure under superhelical stress in vitro and may contribute to the cell type-specific transcriptional regulation of PDGF A-chain gene in vivo.

Base Sequence↗
PubMed1994

Hodgkin's disease associated with chronic myeloid leukemia. Determination of bcr-abl rearrangement in paraffin-embedded tumors using the polymerase chain reaction.

A patient showing lymph node enlargement and tumors in the neck and axilla in the course of Philadelphia (Ph1) chromosome-positive chronic myeloid leukemia (CML) was seen. There were no hematological findings suggestive of crisis. RNA was isolated from formalin-fixed and paraffin-embedded tissue specimens for the polymerase chain reaction of bcr-abl. CML-type products were detected in the peripheral blood, but no bcr-abl products were found in the lymph nodes. These findings indicate a very rare case in which Hodgkin's disease developed during the course of CML.

Base Sequence↗
PubMed1994

[Clinical trial of inhalant recombinant interferon-gamma in patients with pulmonary metastasis from renal tumor (preliminary report)].

Recently, we applied inhalation of recombinant interferon (IFN)-gamma, to 4 patients with pulmonary metastatic tumor (3 with renal cell carcinoma and 1 with renal pelvic tumor). Of the patients with renal cell carcinoma 2 had received previous nephrectomy, 1 patient had received embolization alone, 1 subcutaneous IFN-gamma in 1, and 1 systematic chemotherapy. All 4 patients inhaled 1 x 10(6) JR U-2 x 10(6) JR U recombinant IFN-gamma 3 times per day. Additionally, all metastatic renal cell carcinomas received subcutaneous injection of IFN-gamma. One patient with renal cell carcinoma achieved a complete response after inhalation therapy and 2 patients did not respond (NC: 1, PD: 1). A case of metastatic renal pelvic tumor did not respond. Immunohistochemical staining with antibody to Ber-MAC3 (stimulated macrophage) of this case revealed positive cells within the transitional cell carcinoma. According to these results, inhalation of IFN-gamma appears to be applicable as one treatment for pulmonary metastatic tumor of renal cell carcinoma.

Administration, Inhalation↗
PubMed1994

The potential for bidirectional promoter activity of the human PDGF-A chain gene.

Platelet-derived growth factor (PDGF) is a heterodimeric glycoprotein consisting of A and B chains. A functional promoter had been identified in the 5' flanking region of the human PDGF-A chain gene. We found that the PDGF-A chain promoter region possesses the potential for bidirectional activity. This bidirectional promoter activity is influenced by the 5'-untranslated region (5'-UTR) and serum concentration. The 5'-UTR may regulate expression of the PDGF-A chain by transcription in the opposite direction.

Chloramphenicol O-Acetyltransferase↗
PubMed1994

Identification of 5' regulatory elements of the PDGF-A chain gene, and interaction with single-stranded DNA binding protein.

The expression of platelet-derived growth factor (PDGF) is controlled in a very complicated manner. To clarify the mechanism of regulation of the PDGF-A chain gene, deletion analysis of the 5'-flanking region was performed. We identified a positive regulatory element 25 base pairs (bp) upstream of TATAA, a negative element 135 bp upstream, a positive element 223 bp upstream and a negative element further upstream. These regulatory sites of the PDGF-A chain gene may be involved in tissue specificity, developmental regulation, and transformation. In addition, our analysis suggested the presence of a strand non-specific single-stranded DNA binding nuclear protein in the positive regulatory element 25 bp upstream of TATAA.

Base Sequence↗
PubMed1994

Precise diagnosis by gene analysis and successful management of delivery in three patients with type IIB von Willebrand disease.

Type IIB is a rare variant of von Willebrand disease (vWD). An affected individual's bleeding tendency and thrombocytopenia are exacerbated with pregnancy, and the proper management of these patients during delivery has not been well established. Since it is important to distinguish this disease from the platelet type vWD in order to administer the appropriate therapy, gene analysis is necessary to make the precise diagnosis. We now report the successful management of delivery in three patients, who were diagnosed as having type IIB vWD by the detection of missense mutations in the von Willebrand factor (vWF) gene (C3916-->T and C3922-->T). These changes cause Arg543-->Trp and Arg545-->Cys substitutions in the A1 domain of vWF. We were able to manage the bleeding tendency of these patients at delivery mainly with vWF concentrates to supply normal vWF.

Adult↗
PubMed1994

[Basic and clinical study of platelet-derived growth factor gene expression].

PDGF is a glycoprotein composed of A and B chains, and induced the expression not only in platelets but also in many types of cells. By stimulation inducing cell proliferation, transcription of the A chain is activated, resulting in an increase in mRNA. By stimulation inducing cell differentiation, the A chain is activated at the post-transcriptional level, and the B chain at the transcriptional level, resulting in an increase in both mRNA. The 5' region of the A chain shows a mosaic pattern of positive and negative regulatory elements, suggesting complicated regulation. Also the fragments of the first intron are bond by 110Kd and 90Kd nuclear proteins and regulate the A chain expression. Mechanisms of regulation of the A and B chain gene expression differ markedly. The role of PDGF was then investigated on the mechanism of myelofibrosis frequently observed in myeloproliferative disorders (MPD). In the chronic phase of MPD PDGF was suggested to be leaked or released from megakaryocytes. In the accelerated and blast phase of CML with fibrosis, PDGF-AB or PDGF-BB was found to be secreated from myeloid blasts. These results suggest the importance of PDGF in the pathogenesis of myelofibrosis associated with MPD.

Adult↗
PubMed1994

A patient with anaplastic large cell lymphoma (Ki-1 lymphoma) showing clonal integration of HTLV-1 proviral DNA.

We encountered a patient with anaplastic large cell lymphoma (Ki-1 lymphoma) that originated in the stomach and showed histiocytic lymphoma-like morphology. CD43 antigen was positive, and rearrangement of TCR-beta gene was observed. The lymphoma was the T-cell type. Though no atypical lymphocytes or histological images specific to adult T-cell leukemia were observed, clonal integration of HTLV-1 proviral DNA was noted. Viruses such as HTLV-1 appear to be involved in the development of some anaplastic large cell lymphomas.

Adult↗
PubMed1994

Hemodynamic changes after ligation of a major branch of the portal vein in rats: comparison with rats with portal vein constriction.

In chronic portal-hypertensive rat models, such as portal vein constriction or cirrhosis, the portal blood flow that effectively perfuses the hepatocytes is substantially reduced because of anatomical or functional shunts. It is possible therefore that a feedback mechanism from the liver to the splanchnic bed is responsible for the splanchnic hyperemia observed in chronic portal hypertension. To investigate the possible role of such a feedback mechanism, we examined the chronological changes in both portal and systemic hemodynamics in rats after ligation of a major branch of the portal vein that supplies about 80% of the liver circulation. Rats submitted to sham surgery and portal vein-constricted rats were also studied. Blood flow and portal-systemic shunting were measured by radioactive microsphere techniques. For 7 days after portal-branch ligation, transient portal hypertension resulted from an elevated portal resistance. However, no significant changes in portal venous inflow or splanchnic arteriolar resistance were found in the portal branch-ligated rats, whereas in the portal vein-constricted rats significant hyperdynamic changes in these parameters were noted. On the other hand, transient hyperdynamic changes occurred in the systemic circulation during the period from the fourth to the sixth day after portal-branch ligation, similar to those observed in the portal vein-constricted rats. The lack of hyperdynamic changes in the portal territory of the portal branch-ligated rats suggests that the splanchnic hyperemia found in chronic portal-hypertensive states is unlikely to be caused by a feedback mechanism from the ischemic hepatic parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Primary squamous cell carcinoma of the breast after cured Hodgkin's disease.

An unusual case of primary squamous cell carcinoma of the breast occurring after cured Hodgkin's disease is reported herein. A 27-year-old woman developed a left breast mass 2 years after chemotherapy and radiation for nodular sclerosing stage IIB Hodgkin's disease. Excisional biopsy revealed squamous cell carcinoma of the breast and a modified radical mastectomy was performed, however, no metastasis was found in the axillary nodes. She received etoposide, mitomycin-C, and doxifluoridine as adjuvant chemotherapy, and remains well without any evidence of recurrent Hodgkin's disease or breast cancer. To our knowledge, this is the first reported case of primary squamous cell carcinoma of the breast associated with Hodgkin's disease. The risk of patients treated for Hodgkin's disease developing breast cancer as a second malignant neoplasm is discussed following the report of this case.

Adult↗
PubMed1993

Presence of a regulatory element within the first intron of the human platelet-derived growth factor-A chain gene.

We detected a suppressive element in the first intron of the human platelet-derived growth factor A chain (PDGF-A) gene. Two or more proteins, at least 110-kd and 90-kd proteins, were bound over a wide region of this fragment, and the fragment suppressed the expression of the PDGF-A chain via these proteins in vivo. Since the fragment also had suppressor activity on the promoter of the PDGF-B chain, it may be involved in a suppressive mechanism of gene expression common to PDGF-A and -B chains. Four tandem repeats of CCCCAT(CCCC) and three direct repeats of GGGGAG were observed in this region. The expression of the PDGF-A chain is considered to be regulated by a mechanism involving not only the 5' upstream region but also introns.

Base Sequence↗
PubMed1993

Regulation of the human platelet-derived growth factor B-chain gene.

Human platelet-derived growth factor (PDGF) B chain is a cellular homologue of v-sis, closely involved in cell growth and oncogenicity. Analysis in this study showed the importance of not only the region near the TATAA box but also the fragment -355 bases or more upstream in the expression of the PDGF-B chain gene. However, tissue specificity was not clear in the 5' upstream region alone, and regulation by gene methylation or by elements other than in the 5' region seemed to be necessary. In A172 cells, the half-life of mRNA was much shorter in the PDGF-B chain (< 2 hours) than in the PDGF-A chain (7 hours). Regulation of the PDGF-B chain gene may markedly differ from that of the PDGF-A chain gene not only at the transcriptional level but also at the post-transcriptional level.

Chloramphenicol O-Acetyltransferase↗
PubMed1993

[Immunological effect of recombinant interferon-gamma in renal cell carcinoma].

The immunological effect of interferon-gamma (IFN-gamma) was investigated in 18 cases of renal cell carcinoma before and after the operation. In 6 patients, IFN-gamma was administered preoperatively for 21 days (administration group), while 12 patients underwent nephrectomy alone without preoperative treatment (control group). The peripheral immunological effects were measured at before and 12 days after the operation in the administration group and at 11 days in the control group. In the administration group, a marked increase was noted in the test of antibody dependent cell-mediated cytotoxicity (ADCC) activity and natural killer (NK) activity, and slight increase in CD4/8 and CD11b. In low stage cases, no appreciable effect was obtained by the administration of IFN-gamma. However, in high stage cases, IFN-gamma tended to increase the value of ADCC activity and NK activity. Immunohistochemical studies of tumor infiltrating lymphocytes in renal cell carcinoma showed a high incidence of CD8 and CD11b in the administration group. Moreover, the presence of CD8 was higher than that of CD4 in the administration group in contrast to the results of the peripheral blood analysis.

Carcinoma, Renal Cell↗
PubMed1993

Nucleotide sequence of the 5' region of the human platelet-derived growth factor A-chain gene.

We have isolated and characterized genomic clones of the 5' region of the human PDGF A-chain gene. The putative "TATAA" box was identified 876 bp upstream of the translation initiation site. A significant number of potential regulatory elements were identified in DNA sequences upstream of the "TATAA" box and were also found within the introns sequenced. The DNA sequence results differ significantly from those reported for the PDGF B-chain gene, suggesting a basis for the expression of the PDGF A-chain gene and the B-chain gene under very different conditions.

Amino Acid Sequence↗
PubMed1992

[Observation of the posterior urethra by transrectal linear ultrasonography].

Transrectal linear ultrasonography was performed on 59 male patients with dysuria, and voiding movement of the posterior urethra was observed with a videomonitor. Uroflowmetry was performed simultaneously, and the results were compared with those obtained in a previous study. On the image synchronized with maximum flow rate, the diameter of the bladder neck, and the center of the prostatic urethra were measured as parameters and the correlation with maximum flow rate, average flow rate, and residual urine rate, was examined. The forward movement of the ventral side of the posterior urethra was found to play a more important role in the opening of the posterior urethra, than the opening of the bladder neck, and the width of the prostatic urethra to play a more important role in the efficiency of urination than the width of the bladder neck.

Adult↗
PubMed1992

[Kallmann's syndrome in a child--a case report].

The patient was a male child 6 years and 6 months old. He visited our hospital because of bilateral cryptorchism and true phimosis. Since he was found to have fairly small testis, micropenis, and anosmia, endocrinological examination was performed. The plasma levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were at the lower limit of normal values. LH gave a low reaction to the LH-releasing hormone test, while the reaction of FSH was near the lower limit of normal values. In the human chorionic gonadotropin test, there was no rise in the plasma levels of testosterone. Nor was there any reaction to the venous olfactory test with Alinamine (thiamine propyldisulfide). Accordingly, the patient was diagnosed as having Kallmann's syndrome. A search of the literature reveals few reports that deal with Kallmann's syndrome in infancy. Early diagnosis seems to be of significance, however, to institute early appropriate treatment to prompt the development of proper secondary sexual characteristics and ensure normal future fertility.

Child↗
PubMed1992

[Laboratory and clinical studies on panipenem/betamipron in the field of pediatrics].

Laboratory and clinical studies on panipenem/betamipron (PAPM/BP), a new carbapenem antibiotic, were carried out in the field of pediatrics and the following results were obtained. 1. The antibacterial activities of panipenam (PAPM) against clinically isolated organisms in our department were high overall. 2. After 30 minutes intravenous infusion of PAPM/BP at a dose of 10 mg/10 mg/kg in 1 and of 20 mg/20 mg/kg in 2 children, peak plasma levels of PAPM ranged from 33.21 to 75.66 micrograms/ml at the end of the infusion. The half-lives were 0.81 to 0.93 hours. The cumulative urinary recovery rates in the first 6 hours after the start of drip infusion ranged from 10.7 to 40.4%. 3. PAPM/BP was administered to 16 pediatric patients with various infections. The clinical and bacteriological efficacy rates were both 100%. 4. No side effects were observed. Abnormal laboratory test results were also mild; slight elevation of GOT, GOT/GPT and eosinophylia in 1 each and thrombocytosis in 2.

Age Factors↗