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Biomedical subjects

Y Yamada

Publications and source records attributed to Y Yamada.

At least 37 records · Page 2Linked to original sources

Functional domains of cell adhesion molecules.

A number of molecules involved in cell adhesion (e.g. fibronectin, laminin, collagens I and IV, thrombospondin, entactin) have now been identified and the consequent roles that they play in the processes of growth, migration, differentiation and tumor spread have been described. Active sequences of the molecules have been identified using synthetic peptides derived from specific domains. Several adhesive molecules contain multiple active domains with different biological activities.

Amino Acid Sequence

Interaction of DP-TAT-59, an active metabolite of new triphenylethylene-derivative (TAT-59), with estrogen receptors.

DP-TAT-59, (Z)-2-(4-(1-(4-hydroxyphenyl)-2-(4-isopropylphenyl)-1-butenyl) phenoxy)-N, N-dimethylethylamine, has been reported to inhibit estrogen-stimulated growth of MCF-7 cells as well as rat uterus at lower concentrations than the hydroxymetabolite of tamoxifen (4-OH-TAM). In the present study, the growth of mouse Leydig cell tumor, B-1F cells were also more effectively inhibited by DP-TAT-59 than 4-OH-TAM. Additionally, the expression of estrogen responsive element ligated CAT gene transfected into B-1F cells was also suppressed by DP-TAT-59. Thus, the interaction of DP-TAT-59 with estrogen receptor (ER) was characterized and compared with that of 4-OH-TAM using immature rat and bovine uteri. The dissociation constant of DP-TAT-59 to ER of immature rat uterus was 0.24 nM and was similar to that of 4-OH-TAM (Kd = 0.20 nM) and estradiol (Kd = 0.29 nM). Using sucrose density gradients, the sedimentation constant of DP-TAT-59 with bovine uterus was 4.9S, which was similar to that of estradiol (5.1S) and 4-OH-TAM (5.3S). However, the elution profile of the DP-TAT-59-ER complex from a DEAE-Sephadex column was different for both estradiol-and 4-OH-TAM-ER complexes. These results suggest that ER forms different complexes with DP-TAT-59 than estradiol or 4-OH-TAM, while the ER binding affinity of these compounds are similar to each other.

Animals

Comparison of shape recovery ratios in various intraocular lens haptics.

Since understanding the mechanical properties of intraocular lens (IOL) haptic materials can minimize decentration after surgery, we have examined shape recovery ratios of various intraocular lens haptics (polypropylene [PP], polyvinylidene fluoride [PVDF], extruded poly(methyl methacrylate) [PMMA]) currently on the market under conditions that approximate clinical use. The results using various Ascon lens-holding forceps and compression tests, during which the lenses were held in a cylindrical holder for seven days, one month, and three months, indicated that PVDF haptics had better shape recovery capability than PP and extruded three-piece PMMA haptics.

Lenses, Intraocular

Molecular cloning and partial characterization of a novel collagen chain, alpha 1(XVI), consisting of repetitive collagenous domains and cysteine-containing non-collagenous segments.

In an effort to identify new members of the collagen family, we screened a human placenta cDNA library with a collagenous probe. A novel 3.7 kb cDNA was identified encoding an open reading frame of 1,186 amino acids and containing a termination codon. The predicted polypeptide consists of 9 repetitive collagenous (stretches of Gly-X-Y) and several non-collagenous segments. Two cysteinyl residues separated by two amino acid residues (Cys-X-X-Cys) are regularly located in the N-terminal region of each non-collagenous segment. The deduced amino acid sequence described above is distinct from those of known types of collagen. Therefore, this novel collagen chain is designated alpha 1(XVI). Northern blot analysis revealed an alpha 1(XVI) mRNA of 5.2 kb, indicating that the overlapping cDNA clones isolated in this study covered nearly three-fourths of the mRNA. As a tool for further study on the expression of type XVI collagen, we prepared an antibody against the nonadecapeptide CFLSLERPRAEEARGDNSE, derived from the putative translation product of the cDNA. In immunoblot analysis, the antibody recognized a 160 kDa protein, which was bacterial collagenase-sensitive. Immunohistochemical stainings of human placental tissues with anti-peptide antibody revealed a positive reaction with amnion, the membranous tissue lining the amniotic cavity. The gene of alpha 1(XVI) chain, COL16A1, is mapped on the short arm of human chromosome 1 (1p13-p34).

Amino Acid Sequence

Synthesis and conformation of the trimeric coiled-coil segment of laminin.

A disulfide linked 95-mer parallel hetero-trimeric active site segment of laminin was designed and synthesised. The three subunits, A (32-mer), B1 (30-mer) and B2 (33-mer), were prepared by Boc-based solid-phase peptide synthesis involving a two-step trimethylsilyl bromide-thioanisole and HF deprotection procedure. The interlinking of the three subunits was accomplished by the stepwise selective formation of two disulfide bridges using air-oxidation and thallium (III) trifluoroacetate oxidation. The conformations of the synthetic peptides were studied by circular dichroism (CD) spectroscopy, showing that the hetero-dimer, B1-B2, one of the homo-dimers, B1-B1, and the trimer are 30 to 40% in the alpha-helical conformation in aqueous buffer. Variable temperature CD studies demonstrated that the trimer is considerably more stable (melting temperature (Tm) = 61 degrees) than the hetero-dimer, B1-B2 (Tm = 36 degrees).

Amino Acid Sequence

[Infectious complications in patients with adult T-cell leukemia].

Between January, 1982, and January, 1992, a total of 112 patients with adult T-cell leukemia (ATL) and 109 patients with non-Hodgkin's lymphoma (NHL) were admitted to our hospital. They were studied for their infectious complications. Infectious complications were seen in 90 patients (80.4%) with ATL, and 51 patients (46.8%) with NHL (p < 0.001). Documented infections were seen in 70 patients (62.5%) with ATL, and 30 patients (27.5%) with NHL (p < 0.001). Pneumonia (p < 0.005), skin infections (p < 0.05), Pneumocystis carinii pneumonia (p < 0.05), fungal infections (p < 0.05), cytomegalovirus infections (p < 0.05) and herpes simplex virus infections (p < 0.01) were identified infections at high risk for patients with ATL. Tuberculosis, listeriosis and salmonella infections were seen only in patients with ATL.

Adolescent

[Study on the bacteriological examination of sputum and bronchoscopy specimens from 31 cases with pneumonia due to Chlamydia psittaci].

We carried out the bacteriological examination of sputum and bronchoscopy specimens from 31 cases with pneumonia due to C. psittaci. The results obtained were as follows: 1. The positive culture of sputum and bronchoscopy specimens were 38.7% (12/31). 2. The organisms detected from them were 13 strains of gram-negative bacilli, 2 of gram-positive cocci and one gram-positive bacillus. 3. Significant differences were observed in the white blood cell count between the cases of positive culture and those of normal upper respiratory tract flora (p less than 0.05). From the results we conclude that it would be better that we add the proper antimicrobial drugs to chlamydial antibiotics in the treatment of patients with leukocytosis.

Adolescent

Epidemiology of Tsutsugamushi disease in relation to the serotypes of Rickettsia tsutsugamushi isolated from patients, field mice, and unfed chiggers on the eastern slope of Mount Fuji, Shizuoka Prefecture, Japan.

A total of 59 strains of Rickettsia tsutsugamushi were isolated from patients (24 isolates), Apodemus speciosus mice (30 isolates), and unfed larvae of Leptotrombidium scutellare (2 isolates) and Leptotrombidium pallidum (3 isolates) in the Gotenba-Oyama District, Shizuoka Prefecture, Japan. All these isolates were classified into the three serotypes Karp, Kawasaki, and Kuroki based on reactivity with strain-specific monoclonal antibodies. Kawasaki- and Karp-type rickettsiae were isolated from L. scutellare and L. pallidum, respectively, and the geographic distribution of patients and rodents infected with these two types of rickettsiae coincided with the areas densely populated by the respective chiggers. From these results, we conclude that Kawasaki-type rickettsiae are transmitted by L. scutellare and Karp-type ones are transmitted by L. pallidum. Kawasaki-type rickettsial infections were prevalent in early autumn, and Karp-type infections showed a peak of occurrence in the late autumn, reflecting the seasonal fluctuations of L. scutellare and L. pallidum. Isolates of Kuroki-type rickettsiae were obtained only from four patients in October and November, and the relationship between this type of rickettsia and its vector species could not be fully defined.

Animals

Takayasu's arteritis with collateral circulation from the right coronary artery to intracranial vessels--a case report.

A forty-four-year-old woman with Takayasu's arteritis and involvement of the aortic arch and its main branches complained of precordial pain on effort. Exercise electrocardiograms revealed significant ST segment depression in leads II, III, aVF, and V. Coronary arteriograms demonstrated no stenosis. However, the right coronary arteriogram revealed collateral circulation arising from the sinus node artery to the bilateral vertebral arteries and the left internal carotid artery. The collateral circulation was considered to be an important route of blood flow supply to the brain and, at the same time, a cause of coronary steal syndrome and, consequently, of angina pectoris.

Adult

Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase.

We previously reported the cloning of two distinct somatostatin receptor (SSTR) subtypes, SSTR1 and SSTR2. Although both SSTR1 and SSTR2 bound somatostatin specifically and with high affinity, neither was coupled to adenylyl cyclase, a major cellular effector of somatostatin's actions. Here we report the cloning and functional characterization of a third member of the SSTR family. Human SSTR3 is a protein of 418 amino acids and has 45% and 46% identity with human SSTR1 and SSTR2, respectively. RNA blotting studies showed that SSTR3 mRNA could be readily detected in brain and pancreatic islets. The pharmacological properties of human SSTR3 were characterized by transiently expressing the human SSTR3 gene in COS-1 cells. Membranes from cells expressing human SSTR3 bound the somatostatin agonist [125I]CGP 23996 specifically and with high affinity, with a rank order of potency of somatostatin-28 = CGP 23996 > somatostatin-14 > SMS-201-995. Studies using cells transiently coexpressing the human dopamine D1 receptor and human SSTR3 showed that somatostatin was able to inhibit dopamine-stimulated cAMP formation in a dose-dependent manner, indicating that SSTR3 was functionally coupled to adenylyl cyclase. These results indicate that the diverse biological effects of somatostatin are mediated by a family of receptor with distinct, but overlapping, tissue distributions, unique pharmacological properties, and potentially different functions.

Adenylyl Cyclases

Antitumor agents. I. DNA topoisomerase II inhibitory activity and the structural relationship of podophyllotoxin derivatives as antitumor agents.

Various podophyllotoxin derivatives from desoxypodophyllotoxin (DPT) were synthesized to examine the structural relationships between the biological significance (cytotoxic effect, effects on DNA topoisomerase II and tubulin polymerization) in vitro and antitumor activity in vivo (L 1210). An intact 6,7-methylenedioxy group of DPT is necessary to inhibit tubulin polymerization and topoisomerase II. 4'-Phenolic hydroxyl group of DPT is essential to inhibit DNA topoisomerase II and the inhibitory effect on DNA topoisomerase II contributes to a high cytotoxicity. The introduction of an aminoalkoxy group at 1-position of DPT enhances the inhibitory activity against DNA topoisomerase II and cytotoxic effect, causing the inhibitory activity against tubulin polymerization to disappear. The results of antitumor test in mice bearing L 1210 on podophyllotoxin derivatives suggest the following: 1) the strong cytotoxic effect itself is not a good indication of antitumor activity in vivo as long as it is associated with inhibition of tubulin polymerization. DNA topoisomerase II inhibitory effect contributes to an antitumor activity in vivo; 2) detailed measurements of cytotoxicity and inhibition on DNA topoisomerase II and tubulin polymerization in vitro are necessary to evaluate podophyllotoxin derivatives.

Animals

Heterogeneity of the radiosensitivity and origins of tissue macrophage colony-forming cells.

Previous studies suggest that the radiosensitivity and origin of tissue macrophage precursors differ from those of hemopoietic macrophage colony-forming units (CFU-Ms) committed to macrophage-lineage cells. We assessed the origins of tissue macrophage colony-forming cells (M-CFCs) in mice by comparing their kinetics and radiosensitivities in the normal steady state and under the conditions of bone marrow depletion by 89Sr-administration and/or splenectomy. The results indicate that the radiosensitive peritoneal M-CFCs elicited by thioglycollate are derived from bone marrow macrophage precursors; where as alveolar M-CFCs, which are radioresistant, are self-sustained locally and independent of hemopoietic macrophage precursors. In contrast, highly radiosensitive liver M-CFCs are probably derived from CFU-Ms that appear to be propagated in the spleen in association with hemopoietic responses.

Animals

Effects of instilled fibrogenic particles on the clonal growth of murine pulmonary alveolar macrophages.

Murine pulmonary alveolar macrophages (PAM) form macrophage colonies in vitro with colony-stimulating factors, which stimulate the clonal growth of radioresistant alveolar colony-forming cells (AL-CFC). The toxic effects of fibrogenic mineral dust particles on AL-CFC were investigated after intratracheal instillation into mice. Exposure to either crocidolite asbestos or silica (Min-u-sil) induced a significant depletion of AL-CFC as well as a decrease in PAM recovery compared to either untreated or titanium dioxide-exposed animals. Such effects were also noted with different doses (50-200 micrograms/animal) of instilled particles. The plating efficiency of AL-CFC was depleted in PAM exposed to fibrogenic particles in vitro, but not when exposed to nonfibrogenic titanium dioxide particles. These results indicate the toxic effects of fibrogenic dust particles on the clonal growth of PAM, cells which play a role in the clearance of inhaled particles from the lung and in subsequent pathologic processes.

Animals

Umbilical metastasis from small cell carcinoma of the lung.

Umbilical metastases have been almost exclusively reported in patients with adenocarcinomas of intra-abdominal organs. We present a case of small cell carcinoma of the lung with umbilical metastasis that was confirmed by biopsy. To our knowledge, this is the first reported case of umbilical metastasis from small cell lung cancer.

Aged

Adenosine 3':5'-cyclic monophosphate inhibits in vitro angiogenesis induced by endothelial cell growth factor.

The formation of new blood capillaries (angiogenesis) occurs in response to angiogenic factors released by either normal or tumoral cells. In the present study, we cultured human umbilical vein endothelial cells (HUVEC) on collagen gels and aimed to clarify the effects of cyclic nucleotides on angiogenesis induced by endothelial cell growth factor (ECGF). HUVEC invaded the underlying collagen matrix and formed tube-like structures when ECGF was added. ECGF (9.4 to 75 micrograms/ml) induced angiogenesis in a concentration-dependent manner; the effect reached a plateau at 75 micrograms/ml. Cyclic AMP (10(-3) M), dibutyryl cyclic AMP (10(-3) M), 8-bromo cyclic AMP (10(-5) M) and Sp-cAMPS (10(-3) M), a stimulator of cyclic AMP-dependent protein kinase, each significantly inhibited ECGF-induced angiogenesis by 64.2, 86.1, 46.5, 74.7%, respectively. Forskolin and cholera toxin, which are activators of adenylate cyclase, did not inhibit ECGF-induced angiogenesis. Dibutyryl cyclic GMP (10(-4), 10(-3) M) also did not affect the formation of capillary-like tubes induced by ECGF. In conclusion, cyclic AMP, but not cyclic GMP, inhibits angiogenesis in vitro. This antiangiogenic activity may be applicable to the treatment of such conditions as solid tumors, diabetic retinopathy and rheumatoid arthritis in which the suppression of angiogenesis is important.

Capillaries

Specific expression of glutathione S-transferase Pi forms in (pre)neoplastic tissues: their properties and functions.

The detection of preneoplastic cells is very important for the analysis of carcinogenic processes and for developing strategies for prevention and treatment of cancer. We have been investigating enzyme alterations occurring during rat chemical hepatocarcinogenesis, especially to find more specific enzyme markers for preneoplastic hepatic lesions. We identified the placental form of glutathione S-transferase (GST-P; GST 7-7) as a new marker enzyme for preneoplastic hepatocytes. We also found human placental form, GST-pi, to be a possible tumor marker for various human tissues except liver. In this article, their properties and possible functions are reviewed on basis of our recent investigations. A peroxisomal enzyme, enoyl CoA hydratase, in also described as a possible negative marker for rat preneoplastic hepatic foci/nodules and hepatomas induced by peroxisome proliferators.

Animals

Higher cortical dysfunction, antiphospholipid antibodies and neuroradiological examinations in systemic lupus erythematosus.

We performed neuropsychological tests to investigate higher cortical dysfunction in 21 patients with systemic lupus erythematosus (SLE). We also measured antiphospholipid antibodies (APA), performed brain computed tomography (CT), and obtained a single photon emission CT (SPECT) to measure regional cerebral blood flow (rCBF) in order to elucidate a possible relationship between APA and higher cortical dysfunction. Higher cortical dysfunction was noted in as many as 16 (76%) out of 21 cases. APA were positive in 8 (38%) out of 21 cases. Although the relationship between APA and higher cortical dysfunction was not significant, patients positive for lupus anticoagulant (LA) were found to have higher cortical dysfunction. Brain CT revealed at least one abnormality in 6 cases (29%) but none had a localized lesion, SPECT disclosed a reduced rCBF in 9 cases (43%). The findings on brain CT and SPECT were unrelated to higher cortical dysfunction.

Adolescent

Expression of GLUT1 and GLUT2 glucose transporter isoforms in rat islets of Langerhans and their regulation by glucose.

Previous studies revealed that rat islets express the GLUT2-liver facilitative glucose transporter isoform, a glucose carrier with a low affinity for glucose but a high capacity for glucose transport. These studies indicated the presence of a second glucose transporter in rat islets; however, they did not indicate to which of the five known facilitative glucose transporters it corresponded. In this study, we isolated RNA from rat islets of Langerhans and confirmed the presence of GLUT2 mRNA. In addition, we present data indicating that the second isoform expressed in islets is the GLUT1-erythrocyte isoform. The effect of culturing islets in 5.5, 8.3, or 11.1 mM glucose on the levels of GLUT1 and GLUT2 mRNA also was examined. The levels of GLUT1 and GLUT2 mRNA were two- and threefold higher, respectively, in islets cultured for 24 h in 11.1 mM glucose compared with those incubated in the presence of 5.5 mM glucose. Therefore, the previously observed increase in GLUT2 mRNA levels in the islets of rats made hyperglycemic by chronic infusion of glucose can be mimicked in vitro, implying that glucose regulates GLUT2 mRNA expression.

Animals