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Biomedical subjects

A Yoshimura

Publications and source records attributed to A Yoshimura.

305 records · Page 17Linked to original sources
PubMed1982

[The antigastric ulcer activity of succinic acid mono-3-guaiazulenamide (TPH-3) (author's transl)].

Effects of TPH-3 on various experimental gastric ulcers in rats and guinea-pigs were studied and the following results were obtained. In the preventive experiments, such as the Shay's ulcer, pylorus-ligated aspirin ulcer and restraint and water immersion stress ulcer, TPH-3 (200 mg/kg i.d. or p.o.) showed a statistically significant inhibition. TPH-3 markedly inhibited the histamine-induced gastric ulcer in guinea-pigs and a dose-response relationship was obtained for doses of 12.5, 25 and 50 mg/kg p.o. TPH-3 showed the weak inhibition regarding therapy for serosa-seared gastric ulcer and the recovery process of restraint and water immersion stress ulcer in rats. TPH-3, dosing 100 mg/kg intraduodenally, significantly inhibited the gastric secretion in the pylorus-ligated rats. TPH-3 significantly inhibited the histamine, pentagastrin and carbachol-induced acid secretion in the stomach-perfused rats. In particular, TPH-3 showed strong sensitivity to the action of histamine. TPH-3 had no anti-ACh or anti-H1-receptor effects.

Animals↗
PubMed1981

Effects of ML-236b (compactin) on sterol synthesis and low density lipoprotein receptor activities in fibroblasts of patients with homozygous familial hypercholesterolemia.

We studied biochemical genetics of low density lipoprotein (LDL) receptor mutations in fibroblasts from six homozygous and five heterozygous patients with familial hypercholesterolemia (FH). Three of six homozygotes are receptor-negative type and the other three homozygotes are receptor-defective type. In the cells from three receptor-negative homozygotes, the receptor binding, internalization, and degradation of (125)I-LDL were 0.5+/-0.3 ng/mg protein (mean+/-SEM), 14+/-8 and 8+/-6 ng/mg protein per 6 h (four normal cells; 44+/-3, 386+/-32, and 1,335+/-214 ng/mg protein per 6 h), respectively. In the cells from three receptor-defective homozygotes, the receptor binding, internalization, and degradation of (125)I-LDL were 6+/-2, 29+/-8, and 90+/-32 ng/mg protein per 6 h, respectively. In these six homozygotes, two pairs of siblings are included. Two siblings in the same family were classified as receptor-negative and two siblings in another family were classified as receptor-defective. The receptor-negative phenotypes and the receptor-defective phenotypes bred true in individual families. The cells from five heterozygotes showed approximately 46% of the normal activities of receptor.ML-236B, competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), completely inhibited the incorporation of [(14)C]acetate into digitonin-precipitable sterols in fibroblasts from normal subjects and heterozygous and homozygous patients with FH with the concentration of 0.5 mug/ml. However, at 0.05 mug/ml of ML-236B sterol synthesis in fibroblasts from homozygotes was not completely suppressed in contrast to normal and heterozygous cells. Moreover, after preincubation with 0.05 mug/ml of ML-236B for 24 h in medium containing lipoproteins, sterol synthesis in the cells from receptor-negative homozygote showed 75% of the initial activity compared with that of 25% without preincubation. In the cells from a normal subject and a heterozygote, sterol synthesis was inhibited even after preincubation. These results suggest that (a) the inhibitory effect of ML-236B is overcome in homozygote cells by their high intracellular levels of HMG-CoA reductase and (b) that a higher dose of ML-236B may be required to lower serum cholesterol levels in FH homozygotes than in heterozygotes.

Anticholesteremic Agents↗
PubMed1979

[Microdosimetry of in-flight pi-beams (author's transl)].

Microdosimetry of in-flight pi-beams was performed at the T1 channel of National Laboratory for High Energy Physics (KEK), Tsukuba, Japan. Distributions of lineal energy (y) in-flight pi-beams having six momentum values from 120 MeV/c to 1000 MeV/c were measured with an LET counter which simulates 2 micron sphere of soft tissue filled with the methane base tissue equivalent gas. Frequency spectra were obtained in the range of 1.6 less than y less than 430 keV/micron. Fractional dose y . d(y), cumulative dose D(y), and mean lineal energy were calculated from these spectra; then momentum dependences were investigated. These absolute values have little physical application because of the lack of data for y less than 1.6 keV/micron. However, the general trends of y distribution in momentum dependence were found, qualitatively. As the momentum becomes smaller, the rate of high y component in the dose increased.

Elementary Particles↗
PubMed1978

Dental x-ray spectrometry with an Si(Li) semiconductor.

Spectra from a dental x-ray apparatus with varying tube potentials and various added filters were measured with the use of an Si(Li) semiconductor. The mean energies of the spectra were calculated to estimate radiation qualities under various conditions. A phantom lip made of Arcylite was used to compare the attenuated quantities of radiation incident on the lip, according to the radiation quality, resulting from various tube potentials and added filtration.

Elementary Particles↗
PubMedDate not supplied

Serum lipids, lipoprotein lipids and coronary heart disease in patients with xanthelasma palpebrarum.

Serum lipids and lipoprotein lipids were studied in 53 patients (21 males and 32 females) with xanthelasma palpebrarum and 40 age-matched normal controls (20 males and 20 females). Patients were subdivided into patients with normolipidemia, hyperlipidemia or familial hypercholesterolemia (FH). In both male and female patients with hyperlipidemia or FH, the serum cholesterol (Chol) levels were significantly higher than in normal controls. In both male and female patients with normolipidemia or hyperlipidemia, the VLDL-Chol levels were significantly higher than in normal controls. Male patients with FH showed significantly higher levels of VLDL-Chol than normal controls. Both male and female patients with normolipidemia, hyperlipidemia or FH showed significantly higher levels of LDL-Chol, lower HDL-Chol levels and lower HDL-Chol/LDL-Chol ratios than normal controls. In both male and female patients with hyperlipidemia and in male patients with FH, the serum triglyceride (TG) levels were significantly higher than in normal controls. Both male and female hyperlipidemic patients showed significantly higher levels of VLDL-TG than normal controls. In male patients with FH, the VLDL-TG levels were significantly above the control levels. In male patients with normolipidermia, the LDL-TG levels were significantly higher than in normal controls. In both male and female patients with hyperlipidemia or FH, the LDL-TG levels were significantly higher than in normal controls. The HDL-TG levels in patients with normolipidemia (males) or FH (females) were significantly lower than in normal controls. The prevalence of coronary heart disease in patients with normolipidemia, hyperlipidemia or FH was 29.4%, 24.0% and 45.4%, respectively.

Adult↗
PubMedDate not supplied

Effect of complement activation in human serum on isolated porcine islets.

We investigated the effect of the activation of complement in human serum on isolated adult porcine islets using an in vitro model of pig-to-human islet transplantation. Pancreata were obtained from slaughterhouse pigs (6-8 mo old). Islets were prepared by intraductal collagenase digestion followed by purification on Ficoll gradients. The purified islets were incubated with xenogeneic human serum with or without heat inactivation for 45 min. As control, islets were incubated with autologous porcine serum. After the incubation, the islets' responsiveness to an acute glucose stimulus (5.5 mM, static incubation) was evaluated by measurement of the insulin content of the medium. Islets exposed to human serum showed significantly lower insulin secretory response than the control (1.76 +/- 1.17 microU/islet/120 min, without heat inactivation; 1.74 +/- 1.36 microU/islet/120 min, with heat inactivation; 3.39 +/- 0.92 microU/islet/120 min, control). No difference in insulin secretory response, however, was observed between islets exposed to human serum with heat inactivation and without. Furthermore, we evaluated the cytotoxic activity of human serum on porcine islets by a complement-dependent cytotoxicity using the MTT colorimetric assay, and found that the human serum had no complement-dependent cytotoxic activity against the islets. We concluded that the insulin secretion dysfunction of porcine islets exposed to human serum was not due to the activation of complement and there was no evidence of hyperacute rejection mediated by complement activation in the in vitro model of pig-to-human islet transplantation.

Animals↗
PubMedDate not supplied

Biological aromatization of delta4,6- and delta1,4,6-androgens and their 6-alkyl analogs, potent inhibitors of aromatase.

Enzymic aromatization of delta6- and delta1,6-derivatives of the natural substrate androstenedione with human placental aromatase was first studied using gas-chromatography-mass spectrometry. The two steroids were aromatized with apparent Km and Vmax values of 62 nM and 32 pmol/min/mg protein for the delta6-steroid and 167 nM and 10 pmol/min/mg protein for the delta1,6-steroid, respectively. We next explored the aromatization of a series of 6-alkyl (methyl, ethyl, n-propyl, and n-pentyl)-substituted delta6-androstenediones and their delta1,6-analogs, potent competitive inhibitors of aromatase, to gain insight into the relationships between the inhibitory activity of the 6-alkyl-C19 steroids and their ability to serve as a substrate of aromatase. In a series of the delta1,6-androstenediones, all the 6-alkyl steroids were more efficient substrates than the parent delta1,6-steroid in which the aromatization rates of the alkyl steroids were about 2-fold that of the parent steroid, in contrast, all of the 6-alkyl-substituted delta6-androstenediones were converted into the corresponding 6-alkyl-delta6-estrogens with the rates of less than about a half that of the parent steroid. These results indicate that the 6-alkyl function decreases the aromatization rate of the delta6-steroid but enhances that of the delta1,6-steroid. The relative apparent Km values for the C19 steroids obtained in this study are different from the relative Ki values obtained previously, indicating that a good inhibitor is not essentially a good substrate in the 6-alkyl-substituted delta6- and delta1,6-androstenedione series.

Alkylation↗
PubMedDate not supplied

The CIS family: negative regulators of JAK-STAT signaling.

A family of cytokine-inducible SH2 proteins (CISs) has recently been identified and the members are growing in number. In this family, the central SH2 domain and approximately 40 amino acids at the C-terminus (CIS homology domain; CH domain) are well conserved, while the N-terminal region shares little similarity and varies in length. Most CISs appear to be induced by several cytokines and at least three of them (CIS1, CIS3 and JAB) negatively regulate cytokine signal transduction. Forced expression of CIS1 inhibits STAT5 activation by binding of CIS1 to cytokine receptors, and CIS3 and JAB directly bind to the kinase domain of JAKs, thereby inhibiting kinase activity. Therefore, these CIS family members seem to be present in a classical negative feedback loop of cytokine signaling. They may also play a role in the mutual suppression of cytokine actions frequently found in immune and inflammatory responses. Precise molecular mechanisms of the signal inhibition and their physiological functions will be addressed in the near future. The CH domain is also found in several interesting genes containing WD-40 repeats, SPRY domains, ankyrin repeats, and GTPases. However, the function of the CH domain remains to be determined.

Amino Acid Sequence↗
PubMedDate not supplied

Pilot trial of a combination comprising of consecutive oral administration of UFT, and two-divided administration of CDDP in non-small cell lung cancer.

A pilot study of a combination therapy comprising of consecutive oral administration of UFT, and two-part divided administration of CDDP was undertaken in patients with inoperative non-small cell lung cancer, based on the synergistic effects of CDDP and 5FU. UFT was administered orally at a dosage of 400 mg/m2 for two consecutive weeks (Day 1-Day 14) and CDDP was administered twice by intravenous infusion, once on Day 4 and again on Day 8. The unit dose of CDDP was increased sequentially, from 40 mg/m2 in step 1, to 50 mg/m2 in step 2, and then to 60 mg/m2 in step 3, with safety being confirmed during the process. The numbers of patients registered for each dose level were 3, 3, and 20, respectively. Evaluation of toxicities could be conducted for all the patients except one. No toxicities of grade 3 or higher were observed in step 1 or 2. There was no problem with continuous administration of UFT. The following toxicities of grade 3 or higher were observed in step 3: leukocytopenia in 2 patients; reduction of the hemoglobin count in 1; decrease in creatinine clearance in 2; anorexia in 3; and nausea and vomiting in 3. Bone marrow suppression was mild and transient. Renal failure and digestive symptoms, which were proved to be transient and treatable by symptomatic treatment, were also observed. The step 3 administration was effective in 8 (47.1%) of the 17 patients with measurable lesions (95% CI: 23-71%). In conclusion, since it was determined that the dose employed in step 3 should be recommended and that it could be expected to exhibit antitumour effects with mild bone-marrow suppression, a large scale phase II study should be conducted in no prior treatment non-small cell lung cancer.

Adenocarcinoma↗