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Biomedical subjects

M Ohtsuki

Publications and source records attributed to M Ohtsuki.

At least 19 recordsLinked to original sources
PubMed1992

TGF-beta receptors.

The nature and role of cell surface proteins that bind members of the TGF-beta family has been investigated. TGF-beta, activins, and BMPs each bind to receptors of 55 kDa (type I) and 70 kDa (type II). In the TGF-beta system, these receptors are implicated in the mediation of multiple responses. A member of the type II receptor family has been cloned that encodes four alternatively spliced versions of a transmembrane serine/threonin kinase receptor related to the recently cloned mouse activin receptor and C-elegans daf-1 gene. Inhibitors of serine/threonine kinase activity block transcriptional and growth inhibitory responses to TGF-beta. In addition to the signaling receptors, many cell types express the TGF-beta binding proteoglycan betaglycan. Betaglycan has been purified, molecularly cloned, and shown to bind TGF-beta via its core protein and basic fibroblast growth factor via its heparan sulfate chains. In addition to receptors I and II and betaglycan, some cells express a newly identified set of membrane proteins that specifically bind either TGF-beta 1 or TGF-beta 2. Three of the four isoform-restricted binding proteins are bound to the membrane via phospholipid anchors. Like betaglycan, these proteins might function to regulate the interaction between TGF-beta and their target cells.

Amino Acid Sequence↗
PubMed1992

Losartan, a specific angiotensin II receptor antagonist, increases angiotensin I and angiotensin II release from isolated rat hind legs: evidence for locally regulated renin-angiotensin system in vascular tissue.

The effect of Losartan (10(-9) to 10(-6) M) on angiotensins I and II release was examined in isolated hind legs perfused with Krebs-Ringer solution from normal and bilaterally nephrectomized rats. Losartan increased dramatically both angiotensins I (Ang I) and II (Ang II) release in a dose-dependent fashion; the maximal percent increment in Ang I and Ang II release evoked by Losartan (10(-6) M) was about +380% and +160%, respectively, in normal rat hind legs. In nephrectomized animals, Losartan elicited a marked increase in both peptides dose-dependently. There was a highly positive correlation between the released amounts of Ang I and that of Ang II altered by Losartan in either normal (r = 0.954) or nephrectomized rats (r = 0.923). These results not only confirm the existence of a functional renin-angiotensin system in vascular tissues, but also suggest that the system is regulated by locally generated Ang II.

Angiotensin I↗
PubMed1992

Effects of losartan, a nonpeptide angiotensin II receptor antagonist, on cardiac hypertrophy and the tissue angiotensin II content in spontaneously hypertensive rats.

Losartan, a recently developed nonpeptide angiotensin II (Ang II) receptor antagonist, was administered orally to 10-week-old spontaneously hypertensive rats (SHR) for 2 weeks. Cardiac weight and tissue Ang II, as well as plasma renin activity (PRA) and Ang II, were determined. Treatment with Losartan (10 mg/kg per day) lowered blood pressure markedly. Losartan reduced significantly the left ventricular weight by 11% compared with control rats. The left ventricular Ang II content was lowered by Losartan (18.6 +/- 0.9 pg/tissue; 21.9 +/- 0.9 pg/tissue, control, p less than 0.05), whereas PRA and plasma Ang II concentration were increased by the treatment. With the control and Losartan-treated animals, there was a significant positive correlation between the left ventricular weight and the tissue Ang II content (r = 0.563, p less than 0.05). These results provide evidence that cardiac tissue Ang II, rather than circulating Ang II, plays an important role in the pathophysiology of left ventricular hypertrophy of this animal model of human hypertension.

Analysis of Variance↗
PubMed1992

Nuclear proteins involved in transcription of the human K5 keratin gene.

Keratin K5 is expressed in the basal layer of stratified epithelia in mammals and its synthesis is regulated by hormones and vitamins such as retinoic acid. The molecular mechanisms that regulate K5 expression are not known. To initiate analysis of the protein factors that interact with the human K5 keratin gene upstream region, we have used gel-retardation and DNA-mediated cell-transfection assays. We found five DNA sites that specifically bind nuclear proteins. DNA-protein interactions at two of the sites apparently increase transcription levels, at one decrease it. The importance of the remaining two sites is, at present, unclear. In addition, the location of the retinoic acid and thyroid hormone nuclear receptor action site has been determined, and we suggest that it involves a cluster of five sites similar to the consensus recognition elements. The complex constellation of protein binding sites upstream from the K5 gene probably reflects the complex regulatory circuits that govern the expression of the K5 keratin in mammalian tissues.

Base Sequence↗
PubMed1992

Regulation of epidermal keratin expression by retinoic acid and thyroid hormone.

In the epidermis, retinoic acid (RA) is known to regulate the gene expression of keratins, the intermediate filament proteins of epithelial cells. We have cloned the upstream regulatory regions of three human epidermal keratin genes, K5, K10, and K14, and engineered DNA constructs in which these regions drive expression of the CAT reporter gene. By co-transfecting the constructs into various epithelial cell types along with the vectors expressing the nuclear receptors for RA and thyroid hormone (T3), we have shown that RA and T3 directly regulate expression of these three keratin genes through the action of their nuclear receptors. In this paper, we review our previous results to stress that RA has a dual effect on keratin expression in epidermis: both direct and indirect. We also analyze the DNA sequences upstream from those three RA-regulated keratin genes and identify the clusters of degenerate consensus half-site motifs, which may comprise the putative retinoic acid recognition elements (RAREs). Furthermore, our recent results concerning the regulation of K5 and K14 expression by the RA receptor are also shown; these confirm our predictions regarding the location of the RAREs in epidermal keratin genes.

Base Sequence↗
PubMed1992

Evidence for the involvement of protein kinase activity in transforming growth factor-beta signal transduction.

Transforming growth factor-beta 1 (TGF-beta 1) rapidly increases the expression of junB transcription factor and plasminogen activator inhibitor-1 (PAI-1) and prevents the cell cycle-dependent phosphorylation of the RB retinoblastoma susceptibility gene product during late G1 phase in Mv1Lu lung epithelial cells. These responses are shown in this report to be blocked by the potent serine/threonine protein kinase inhibitor, H7, added with TGF-beta 1. Added alone, H7 does not alter the basal junB or PAI-1 mRNA levels, the deposition of PAI-1 into the extracellular matrix, or the phosphorylation of RB in late G1 phase, suggesting that this inhibitor does not have a general nonspecific effect on the cell. The analogs H8 and H9, which are preferential inhibitors of cyclic nucleotide-dependent protein kinases, are fivefold less potent than H7 as inhibitors of the TGF-beta response. The PAI-1 response to TGF-beta 1 is not affected by the simultaneous addition of staurosporine, which is a protein kinase C inhibitor, or by the prolonged preincubation of cells with phorbol 12-myristate 13-acetate, which down-regulates protein kinase C. The results suggest the possibility that H7 and its analogs block various early TGF-beta responses by inhibiting a protein serine/threonine kinase(s).

Animals↗
PubMed1991

Responsiveness to interleukin 4 and interleukin 2 of peripheral blood mononuclear cells in atopic dermatitis.

Although the pathogenesis of atopic dermatitis (AD) is unknown, many immunologic abnormalities such as high levels of serum IgE and increase of IgE Fc receptor-positive lymphocytes have been demonstrated. Recently, interleukin 4 (IL-4) has been shown to induce enormously the production of IgE and to enhance the expression of IgE Fc receptor by B cells, suggesting the possible involvement of IL-4 in the pathogenesis of AD. We examined IL-4 responsiveness or interleukin 2 (IL-2) responsiveness of peripheral blood mononuclear cells of 31 patients with AD, 19 healthy individuals, and seven patients with other skin diseases. We found that IL-4 responsiveness of AD was higher than that of non-AD control, although IL-2 responsiveness of AD showed no significant change. However, the value of the IL-4 responsiveness did not significantly correlate with the clinical severity, personal history of respiratory allergy, serum IgE level, or clinical course of patients with AD. The hyperresponsiveness to IL-4 detected in AD was not likely to be due to the effects of steroids or anti-mast cell drugs because the value of IL-4 responsiveness was significantly low, compared to AD, in patients with other skin diseases who were treated similarly. Because the T-cell-enriched population, but not the B-cell-enriched population, showed significant proliferation in response to exogenous IL-4 or IL-2, T cells were the main population that reacted in our proliferation assay. These results indicate that IL-4-driven proliferative response may be efficiently operative in T cells in patients with AD.

B-Lymphocytes↗
PubMed1990

Membrane fusion events during endocytosis in mouse kidney tubule cells detected by rapid freezing followed by freeze-substitution.

Membrane fusion events during endocytosis were examined in renal proximal tubule cells processed by rapid freezing followed by freeze-substitution. An extensive fusion site of the membranes between two apical vacuoles or a vacuole and a lysosome, which appeared as a pentalaminar structure, was not observed in this study, though such a pentalaminar structure has been found in chemically fixed specimens. In vitro experiments using subcellular fractions revealed that the pentalaminar structure did not always represent the initial stage of membrane fusion. Membrane fusion appeared to occur in a specific membrane site, wHere a minute pore connecting the two lumens was formed immediately after the two membranes came into contact with each other. Some pore necks showed an asymmetrical feature which consisted of a sharp corner and a gently curved corner. Enlargement of the pore appears to be mediated by a fibrous structure observed near the sharp corner of the pore neck.

Animals↗
PubMed1989

Solid phase synthesis of oligoribonucleotides using the 1-[(2-chloro-4-methyl)phenyl]-4-methoxypiperidin-4-yl (Ctmp) group for the protection of the 2'-hydroxy functions and the H-phosphonate approach.

The solid phase synthesis of oligoribonucleotides using the H-phosphonate approach and the 1-[(2-chloro-4-methyl)phenyl]-4-methoxypiperidin-4-yl (Ctmp) and dimethoxytrityl (DMTr) groups, respectively, for the protection of the 2'- and 5'-hydroxy functions is described. The use of a new reagent, tris-(1,1,1,3,3,3-hexafluoro-2-propyl) phosphite for the preparation of nucleoside H-phosphonate units is also discussed in detail.

Base Sequence↗
PubMed1989

[Clinical study on the prognosis of complete denture wearers covering 10 years. 3. Fitness test of the complete denture base].

The purpose of this study was to estimate the clinical condition of complete denture wearers. 72 patients came to our Dental Hospital according to our recall. The examination consisted of a questionnaire and clinical examinations. For objective evaluation, the fitness test of lower complete denture base was taken place and was classified into four groups by the thickness of the white-silicone film (A-zone 0-30 microns, B-zone 30-70 microns, C-zone 70-130 microns, D-zone 130 microns-). Results 1. The average ratio of four groups of the white-silicone film were A-zone 9.3%, B-zone 35.8%, C-zone 24.5% and D-zone 30.4%. 2. The fitness of anterior portion was ill fit in comparison with posterior portion. 3. There was statistically significant difference between the fitness of lower complete denture and dentist's judgment diagnosed as ill fit denture. 4. There was significant difference between the fitness test and the patients who complained about loose fit of the denture.

Denture Bases↗
PubMed1989

[Solvent power of new denture cleaner for denture calculus and the influence of this cleaner on the denture materials].

In order to chemically remove the calculus adhering to a denture, new denture cleaner was prepared on an experimental basis. The principal ingredient of this solution was a chilating agent which contained the phosphoric acid. This study consisted of the fundamental and the clinical examinations of this solution the purpose of which was to test the solvent power of this solution on the calculus and to evaluate its influence on the denture materials and its effectiveness in clinical practice. 1. the fundamental study 1) method (1) The test for the solvent power of this solution. The powder of tricalcium phosphate (T.C.P. powder: Wakohjunyaku Co.) was substituted for the calculus adhering to a denture. (1) The influence of the solution temperature on the solvent power. The T.C.P. powder was dissolved at 20 degrees C, 30 degrees C, 40 degrees C, 50 degrees C and 60 degrees C temperature in 10 g of the solution within 10 minutes and the amount of dissolved powder was weighted. The time was measured with a stop watch (Seiko Co.) until 0.5 g of T.C.P. powder had been dissolved in 10 g of the solution. (2) The effect of using it with an ultrasonic cleaner. The time to dissolve 0.1 g of T.C.P. powder in 10 g of this solution was compared with that of the 15% EDTA solution. The measurement was repeated 5 times and the arithmetic mean of the 5 sample values was calculated in order to show the experimental results. The room temperature was 19 +/- 2 degrees C, the humidity was 56 +/- 3%. (2) The influence of this solution on the denture materials. (1) resin specimen. In order to test the transverse strength, transverse deflection, Young's modulus and Knoop hardness, resin specimens were processed in the manner specified in I.S.O. 1567. The data were compared the resin specimens steeped in this solution and with the control sample that was steeped in water. The specimens were immersed up to 24 hours. Furthermore the existence of tarnish was observed with a 40 times microscope. (2) metal specimen. In order to test the corrosion, metal specimens were produced according to the manner of a corrosion test. The metal specimens were held vertically and the end immersed to 20 mm in this solution for 24 hours and 120 hours each. After steeping, each specimen was measured for loss in weight. The data were calculated as the loss in weight per hour (mg/cm) and the depth of corrosion per year (mm/yr).(ABSTRACT TRUNCATED AT 400 WORDS)

Corrosion↗
PubMed1989

[Cellular immunoregulation in atopic dermatitis--hyperresponsiveness to interleukin-4 and hyporesponsiveness to interleukin-2].

We examined the responsiveness to Interleukin-4 (IL-4) and Interleukin-2 (IL-2) of peripheral blood lymphocytes from patients with atopic dermatitis (AD) and non-AD controls. The IL-4 responsiveness of the AD patients was found to be higher than that of the non-AD controls. In contrast, the IL-2 responsiveness of the AD patients was relatively lower than that of the non-AD controls. When IL-4/IL-2 responsiveness ratio was compared, the IL-4/IL-2 responsiveness ratio of the AD patients (54.1 +/- 18.5) was significantly higher than that of the non-AD controls (24.8 +/- 9.9, p less than 0.001). The high IL-4/IL-2 responsiveness ratio found in the AD patients may possibly be related to the pathogenesis of AD.

Adolescent↗
PubMed1986

Transcription factor(s) of Ehrlich ascites tumor cells having affinity to the 'TATA' box and a further upstream region of the adenovirus 2 major late gene.

A fraction containing a transcription factor(s) of RNA polymerase II was prepared from a nuclear lysate of Ehrlich ascites tumor cells and its binding to a promoter region of the adenovirus 2 major late gene was examined. Results showed that this fraction contained a factor(s) binding to two distinct regions: a region including the 'TATA' box and another region further upstream. The upstream protected region was different from that reported to be protected by a HeLa cell factor, suggesting species specificity of transcription factor(s) in DNA binding.

Adenoviruses, Human↗
PubMed1986

In vitro transcription of a chromatin-like complex of major core protein VII and DNA of adenovirus serotype 2.

Major core protein VII of adenovirus serotype 2 (Ad2) is thought to play a role as a histone octamer in eukaryotic cells. We compared the template activity of the VII-DNA complex formed in vitro with that of protein-free DNA. Hybridization assay of in vitro transcripts showed that transcription from regions located in the middle of Ad2 DNA decreased when Ad2 DNA formed a complex with VII. This suggests that the chromatin structure plays a role in regulation of transcription of the adenovirus genome.

Adenoviridae↗