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Biomedical subjects

H Osada

Publications and source records attributed to H Osada.

At least 199 records · Page 11Linked to original sources

The LIM protein RBTN2 and the basic helix-loop-helix protein TAL1 are present in a complex in erythroid cells.

Chromosomal translocations in T-cell acute leukemias can activate genes encoding putative transcription factors such as the LIM proteins RBTN1 and RBTN2 and the DNA-binding basic helix-loop-helix transcription factor TAL1 associated with T-cell acute lymphocytic leukemia. While not expressed in normal T cells, RBTN2 and TAL1 are coexpressed in erythroid cells and are both important for erythroid differentiation. We demonstrate, using anti-RBTN2 and anti-TAL1 antisera, that the LIM protein RBTN2 is not phosphorylated and is complexed with the TAL1 phosphoprotein in the nucleus of erythroid cells. A complex containing both RBTN1 and TAL1 also occurs in a T-cell acute leukemia cell line. Since both RBTN2 and TAL1 are crucial for normal erythropoiesis, these data have important implications for transcription networks therein. Further, since both proteins can be involved in leukemogenesis, these data provide a direct link between proteins activated by chromosomal translocations in T-cell acute leukemia.

Adaptor Proteins, Signal Transducing↗

Cysteine-rich LIM domains of LIM-homeodomain and LIM-only proteins contain zinc but not iron.

The structure of LIM domains has major implications for transcription because proteins such as Is1-1 contain two LIM domains associated with a homeodomain, and RBTN1/Ttg-1 and RBTN2/Ttg-2 contain two LIM domains but no homeodomain. Conserved cysteine and histidine residues in the LIM domains suggest a metal-binding role. RBTN and Is1-1 LIM proteins have been made in Escherichia coli and insect cell expression systems and their metal content has been determined using atomic absorption spectroscopy and electron paramagnetic resonance spectroscopy. LIM proteins expressed in soluble form contain zinc atoms, whereas bacterial inclusion bodies invariably also have Fe-S clusters. The latter are identified as linear [Fe3S4]+ clusters and appear to result from incorrect metal coordination by E. coli. These studies show that RBTN1, RBTN2, and Is1-1 are metalloproteins that contain zinc but not iron and, therefore, that the LIM domain represents a zinc-binding domain.

Cysteine↗

Effect of gonadotropin-releasing hormone agonist on the bone mineral density of patients with endometriosis.

OBJECTIVE: To examine changes in bone mineral density (BMD) of patients treated with GnRH agonist (GnRH-a) by dual-energy X-ray absorptiometry and to understand factors related to bone loss. DESIGN: Prospective controlled trial examining BMD during and after GnRH-a therapy every 24 weeks for 18 months in patients with endometriosis compared with nontreated controls. SETTING: Outpatients clinic at a university hospital and its affiliated outpatient clinic. PATIENTS: Twenty-two patients with endometriosis as GnRH-a-treated group, 12 healthy women with normal menstrual cycle, and 7 patients with mild endometriosis as control group. INTERVENTIONS: Patients were treated with a GnRH-a (buserelin acetate) at 900 micrograms/d by nasal spray for 24 weeks. RESULTS: The significance of differences in change-rates at all measured points in both groups was assessed by analysis of variance. The interaction between treatment and period was significant, and only week 24 of the GnRH-a-treated group was significantly lower compared with baseline. The reduction rate of BMD was high in patients 33 years of age or younger compared with those who were 34 years of age or older. According to a multiple-regression model, the most important factor related to bone loss was the post-treatment serum levels of E2. CONCLUSION: At the end of treatment, BMD was significantly lower than that of the control group, and the reduction rate was 3.4%. A factor related to bone loss was degree of ovarian suppression.

Adult↗

The first step of experimental study on hybrid trachea: use of cultured fibroblasts with artificial matrix.

Anastomotic stenosis secondary to developing granulation tissue prevents an artificial trachea of non-porous type model from a safe practical use. Taira reported that a non-porous artificial trachea having soft ends for anastomosis works better in this regards apparently by cushioning mechanical stimulations repeatedly applied to the anastomotic rings than most models ever studied have done. We hypothesized that hybridization of soft anastomotic ends of nonporous artificial trachea may further prevent granulation tissue at the anastomoses hopefully by leading epithelial growth earlier onto the inner surface of graft's ends. The graft of our use was made of a 5-cm-long knitted dacron tube with inner coating with silicone rubber covering the entire length but for a 5 mm segment at each end. To date six mongrel dogs have been subjected to test this hypothesis. A piece of subcutaneous tissue was obtained from each dog and prepared for culture of fibroblasts in MEM. These fibroblasts were then suspended in 0.1% collagen with MEM in a container, in which a graft was placed for further culture. Following some 3 weeks of this preparation each graft was implanted to replace a 10-cartilage-ring-long defect of the mediastinal trachea of each donor dog. One dog is enjoying active life 11 months postop, and another 3 months. Four dogs died from anastomotic stenosis 2 to 3 months. Being encouraged by the fact that the anastomotic rings of the long term survivors show bronchoscopically patency more than 40% of cut surface area, and some portion with possible epithelialization without granulation, we will report our further results, along with histological study.

Animals↗

Inhibitory action of epiderstatin on EGF-stimulated growth of mouse epidermal. BALB/MK cells without direct effect on protein kinase activities.

Epiderstatin, a distinctive glutarimide antibiotic isolated from Streptomyces pulveraceus subsp. epiderstagenes, has been revealed to be a potent inhibitor of the signal transduction of epidermal growth factor (EGF). Epiderstatin inhibited the DNA synthesis induced by various peptide growth factors in a mouse epidermal cell line, BALB/MK, without inhibiting protein tyrosine kinase activity of EGF-receptor or serine/threonine kinase activity of protein kinase C. The 50% inhibitory concentration (IC50) value of epiderstatin for the EGF-stimulated incorporation of [3H]thymidine into BALB/MK cells was about 10 nM. When epiderstatin was added to the quiescent cells simultaneously with EGF-stimulation, the cells did not reenter into the growing cell cycle. The action of epiderstatin proceeded from the overexpression of c-fos and the suppression of c-myc transcription when EGF was added to quiescent BALB/MK cells.

Actins↗

[Successful neoadjuvant chemotherapy in a patient with advanced gastric cancer with multiple liver metastases].

We described a case of advanced gastric cancer with multiple liver metastases, who was placed on neoadjuvant chemotherapy using CDDP and 5-FU (FP therapy) with a marked reduction in tumor load. The case was a 67-year-old male, who was admitted with a Borrmann III type advanced gastric cancer with multiple liver metastases. FP chemotherapy was carried out two times as neoadjuvant chemotherapy. As a result, both primary cancer and the metastatic tumors showed a remarkable reduction. Then, total gastrectomy with combined resections of spleen and transverse colon was done, and a reservoir was inserted into the hepatic artery. Postoperatively, intrahepatic arterial infusion of CDDP with oral administration of 5-FU was done in the outpatient clinic for about eleven months. But thirteen months later, he died from the rapid recurrence of the tumor.

Adenocarcinoma↗

[Surgical advancements in reproductive medicine with emphasis on tubal disorders].

Achieving patency of the Fallopian tubes by selective transcervical hysterosalpingography, transcervical tuboplasty using PTCA-balloon catheters and microsurgical techniques has a success rate in excess of 90%, however, the pregnancy rates following these procedures is still less than 50%. Thus, the surgical approach for the treatment of tubal infertility which may improve post therapeutic pregnancy rates remain as yet unsolved problems. Modalities proposed include tubal transplants and prosthetic functional tubes. The purpose of surgical approaches to treat tubal infertility is to regain the physiologic ability to become pregnant without further clinical intervention. This has the advantage of reducing both economic and psychologic stress in the previously infertile couple, thus is clinically highly desirable, when achievable. However as there are limits for the indications of these procedures, for instance in occluded tubes, where disease has caused irreversible damage to the tubal endothelium, physical restoration of patency may not restore fertility. Thus, this discussion covers the limitations of surgical procedures and alternate procedures when surgical procedures are inadequate. We further investigated the tubal influences on the establishment and development of the zygote, and the tubal influences such as pressure and exudate dynamics on their transport within the tube. Thus, the advances in enhanced fertility studies, including in vitro fertilization have led more definitive understanding of fertilization, development of the zygote and its nidation, necessitating more intensive investigation of tubal physiology. In conclusion, where possible, surgical procedures which may allow physiologic pregnancies without additional clinical intervention are an attractive approach which should be utilized maximally when acceptable pregnancy rates can be expected.

Fallopian Tube Diseases↗

Spleen-derived growth factor, SDGF-3, is identified as keratinocyte growth factor (KGF).

A heparin-binding mitogen rat for rat hepatocytes was partially purified from bovine spleen by a combination of heparin-affinity, cation-exchange and gel-filtration chromatography. Besides stimulating rat hepatocytes, this factor, which was designated spleen-derived growth factor-3 (SDGF-3), exhibited mitogenic activity for mouse epidermal keratinocytes but not mouse fibroblasts. Its apparent epithelial specificity and heparin-binding properties corresponded to those of keratinocyte growth factor (KGF). These findings, together with the fact that the mitogenic activity of SDGF-3 was abolished by a neutralizing monoclonal antibody specific for KGF, identify this bovine spleen-derived hepatocyte mitogen as KGF.

3T3 Cells↗

The cysteine-rich LIM domains inhibit DNA binding by the associated homeodomain in Isl-1.

Recently, a new class of homeobox genes has been identified, called LIM-homeobox genes. These genes encode proteins which have two tandemly repeated cysteine motifs, referred to as LIM domains, in addition to a homeodomain. In addition, proteins with only LIM domains have been described but the function of the LIM domain is unknown. We have analysed the function of LIM domains using Isl-1 as a representative LIM-homeodomain protein. Employing protein prepared in bacterial cells, we show that the presence of the LIM domain in Isl-1 inhibits binding of the homeodomain to its DNA target. This in vitro inhibition can be released either by denaturation/renaturation of the protein or by truncation of the LIM domains. A similar inhibition is observed in vivo using reporter constructs. In addition we show that LIM domains in a chimeric protein can inhibit binding of the Ubx homeodomain to its target. The ability of LIM domains to inhibit DNA binding by the homeodomain provides a possible basis for negative regulation of LIM-homeodomain proteins in vivo.

Base Sequence↗

Respinomycins A1, A2 B, C and D, a novel group of anthracycline antibiotics. I. Taxonomy, fermentation, isolation and biological activities.

Respinomycins are a novel group of anthracycline antibiotics produced by Streptomyces xanthocidicus. Respinomycins A1, A2, B, C and D were isolated by EtOAc extraction, silica gel column chromatography, centrifugal partition chromatography and preparative silica gel thin layer chromatography. Respinomycins A1 and A2 induced the terminal differentiation of human leukemia K-562 cells.

Animals↗

Respinomycins A1, A2, B, C and D, a novel group of anthracycline antibiotics. II. Physico-chemical properties and structure elucidation.

Respinomycins A1, A2, B, C and D were revealed to be novel anthracycline antibiotics with molecular formulae of C51H72N2O20, C43H58N2O15, C35H43NO14, C36H45NO14 and C51H70N2O22, respectively. Their structures were determined by means of 1H-1H COSY, 13C-1H COSY and HMBC spectra. The structure of the aglycone of respinomycins was unambiguously determined by LSPD experiments and NOESY. The common skeleton of respinomycins is a new type and is distinguished from that of the nogalamycin group.

Anthracyclines↗

[Dual-energy data acquisition for simultaneous 81mKr ventilation/99mTc-MAA perfusion SPECT: ventilation/perfusion ratio mapping in cross section].

Methods of simultaneous pulmonary ventilation/perfusion (V/Q) tomogram (SPECT) for V/Q ratio mapping were reported. Crosstalk was corrected by subtraction assuming crosstalk/signal ratio is constant for an individual examination. Crosstalk was reduced by 85% for that of 99mTc-to-81mKr window (R12), and by 83% for that of 81mKr-to-99mTc window (R21) in a phantom experiment. The R12 and R21 were 1.0-1.9% (mean 1.3%) and 34.6-55.3% (mean 41.9%), respectively in 9 patients (mean age, 56.1 years; range, 38-82 years). V/Q SPECT was undertaken in 7 of the 9 patients. 99mTc-macroaggregated albumin (185 MBq) was injected intravenously in supine position, and 81mKr gas was administered continuously during the SPECT data acquisition. Sixty-four 64 x 64-matrix (size = 8 mm/pixel) images, 20-second acquisition time for each, were collected by a rotating gamma camera in a step-and-shoot fashion during a 360-degree rotation with the two photopeaks, one at 140 keV for 99mTc and another at 190 keV for 81mKr. Examination time was about 40 minutes, and the V/Q ratio maps in cross section were obtained in all of the examinations.

Adult↗

[Radionuclide studies of atherosclerosis].

New Tc-99m-labeled brain perfusion imaging agents, such as Tc-99m-HMPAO, and Tc-99m-ECD, are developed and expected to improve the clinical study of cerebral perfusion disturbance due to arteriosclerosis. They enable us better images than I-123-IMP and more accurate diagnosis. Similarly, in the field of cardiovascular nuclear medicine, new Tc-99m-labeled compounds, Tc-99m-MIBI, Teboroxime and Tetrofosmin are available. Furthermore, I-123-MIBG, a tracer taken up in presynaptic adrenergic vesicles, and I-123-BMIPP, a new agent developed for the evaluation myocardial fatty acid metabolism, will mark a new epoch in the study of coronary sclerosis. In order to image atherosclerosis directly, In-111-polyclonal immunoglobulin G, Tc-99m-low density lipoprotein etc., are under investigation.

Amphetamines↗

An experimental study of osteogenesis by autografted dental pulp, periodontal ligament, and bone marrow in vivo.

Osteogenic activity of autografted dental pulp, periodontal ligament, and bone marrow of rat in vivo was investigated. Immunolocalization of ALPase in situ was also studied. One month after the transplantation, osteodentin was formed in all the dental pulp transplants (100%), bone or cementum like tissues were created in 20% of periodontal ligament transplants, and bone like tissues were in 20% of bone marrow transplants. After two months, osteodentin was produced in all the dental pulp transplants (100%) and bone like tissue were in 50% of both periodontal ligament and bone marrow transplants. Immunohistochemically, positive reactions to ALPase in situ were detected in cells just below the odontoblast layers in dental pulp, surface layers of alveolar bone in periodontal ligament, and endosteal membrane of bone marrow space. From these results, it was suggested that the cells of these three kinds of tissue can be termed osteogenic-fibroblasts in vivo.

Alkaline Phosphatase↗