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Biomedical subjects

S Aoyama

Publications and source records attributed to S Aoyama.

At least 37 records · Page 2Linked to original sources

Indole derivatives as a new class of steroid 5 alpha-reductase inhibitors.

A series of indole derivatives with varied substituents on the alpha, beta-unsaturated double bond were synthesized and evaluated for their ability to inhibit rat prostatic 5 alpha-reductase. Compounds possessing an ethyl substituent at the beta-position of the double bond showed potent inhibitory activity. Among them, (Z)-4-{2-[[3-[1-(4,4'-difluorobenzhydryl)indol-5-yl]-2-pentenoy l]- amino]phenoxy}butyric acid (16, KF20405) showed the maximum potency with an IC50 value of 0.48 +/- 0.086 nM, which was 20-fold higher potency than 1 (MK-906). Compound 16 effectively inhibited DHT production 4 h after a 3 mg/kg oral administration. Several potent indole derivatives, 1 and 2 ((+/-)-ONO-3805), were tested versus rat and human isozymes. Nonsteroidal inhibitors such as indole derivatives and 2 were 2-3 orders of magnitude less potent for human type 2 isozyme than steroidal inhibitor 1 and expressed a significant species deference for these isozymes.

5-alpha Reductase Inhibitors↗

Morphometric study on the fetal thyroid gland in the nude mouse (BALB/cAnNCrj-nu/nu).

Fetal thyroid glands of athymic nude mice (BALB/cAnNCrj-nu/nu) were examined morphometrically on day 18 of gestation. Compared to euthymic litter mate controls (BALB/ cAnNCrj-nu/+), both the cell height and diameter of thyroid follicles were significantly smaller; fewer well-developed follicles were found in the peripheral region of the thyroid; the body weight and total volume of the thyroid gland were also smaller in nude mice. These results suggest underdevelopment of the fetal thyroid gland of the athymic nude mouse.

Animals↗

[Clinical study of ten cases with acute abdomen after eating raw firefly squid (Watasenia scintillans, Hotaruika), which are probably due to type X larvae of the suborder spirurina].

We studied ten cases with abdominal pain after eating raw firefly squid, Watasenia scintillans, Hotaruika. Characteristic clinical features were abdominal pain, nausea, vomiting, diarrhea, creeping eruption and ileus with ascites. In ten patients, there were all cases with abdominal pain, nine with nausea and vomiting, four with diarrhea, one with creeping eruption, six with ileus. Laboratory examination revealed eosinophilia on peripheral blood in ten cases and high serum IgE value in nine cases. The infection rate of type X lavae of the suborder spirurina in Watasenia scintillans is almost 3%, so we measured the antibody to type X larvae of the suborder spirurina in nine patients by indirect fluorescent antibody method and the antibody titer was positive in seven cases. Most patients recovered in several days from first visit. But one patient was diagnosed peritonitis and operated with partial ileectomy. Pathological finding of resected specimen showed an erosion in the mucosal layer and an inflammation with marked eosinophilia in the submucosal layer. These results suggest that abdominal complaints after eating Watasenia scintillans are due to type X larvae of the suborder spirurina.

Abdomen, Acute↗

[Marked dilatation of the bilateral common carotid artery: a case report].

We reported a rare case of marked dilatation of the bilateral common carotid artery (CCA) associated with stenosis of the left middle cerebral artery (MCA). A 64-year-old female was admitted with right hemiparesis and dysarthria. She was hospitalized 2 years ago for cholecystitis. For 5 years, she has been under medical treatment for hypertension, diabetes mellitus, hyperlipidemia, cardiac failure associated with hypertrophic cardiomyopathy, and atrial fibrillation. Brain CT scan showed infarction of the left corona radiata. Angiography revealed marked dilatation of the bilateral CCA and the internal carotid artery (ICA), moderate dilatation of the innominate artery and the right subclavian artery, kinking of the right CCA, diverticular outpouching of the left ICA, and stenosis of the right external carotid artery and the left MCA. Breast CT scan revealed moderate dilatation and marked calcification of the ascending aorta and the aortic arch. Laboratory examination did not show any sign of inflammation, rheumatoid factor (RA), antistreptolysis-O (ASLO) and antinucleotic antibody. Based on the clinical course, radiological findings and laboratory data, possible diagnosis of the dilatation of the bilateral CCA was discussed with particular emphasis on arteriosclerotic aneurysm and aortitis syndrome.

Aortic Arch Syndromes↗

Targeted pituitary tumorigenesis using the human thyrotropin beta-subunit chain promoter in transgenic mice.

We have generated transgenic mice that express the simian virus 40 (SV40) large T antigen under the control of a 1109 bp 5'-flanking sequence of the human thyrotropin beta-subunit (TSH beta) gene. The hybrid gene, termed TTP-1, was microinjected into fertilized mouse eggs and 11 transgenic mice were obtained. One of the transgenic mice, a female, a phenotypical dwarf, developed a pituitary tumor and wasted away from 7 to 9 weeks after birth. To establish the transgenic mouse line, her ovaries were transferred to a normal female, whose ovaries were removed beforehand. To examine the tissue specificity of transgene expression, mRNA of SV40 large T antigen was monitored in various tissues from the transgenic mice by the reverse transcriptase-polymerase chain reaction analysis, and was detected only in the pituitary. Histological and immunohistochemical analyses showed that the pituitary tumors of the transgenic mice were composed of poorly differentiated pituitary cells expressing SV40 large T antigen. These results indicated that the 1109 bp sequence of the human TSH beta 5'-flanking region is essential for pituitary-specific expression of SV40 large T antigen in transgenic mice, which exhibited a dwarf phenotype and developed pituitary tumors. The tumors were composed of undifferentiated cells and did not produce thyrotropin. These transgenic mice should provide a valuable animal model for studying the pathogenesis of anterior pituitary tumors.

Animals↗

Cloning and DNA sequence of a 29 kilodalton polypeptide gene of Mycoplasma gallisepticum as a possible protective antigen.

A lambda gt11 clone, designated M1 and having a 0.8 kilobase (kb) insert, was selected by screening a Mycoplasma gallisepticum (M.g.) genomic DNA library with antisera against M.g. cells and their membrane proteins. The sequence of a 1.7 kb EcoRI fragment of genomic DNA covering the entire M1 insert revealed a long open reading frame, TM-1, that encoded a polypeptide with a deduced molecular weight of 29 kDa. An antiserum raised in chicken against the TM-1 polypeptide, which was produced by recombinant Escherichia coli cells and purified by column chromatography, inhibited growth of M.g. cells in vitro. Moreover, chickens immunized with this polypeptide were partially protected from a challenge with virulent M.g. This polypeptide may serve as the basis for a vaccine against M.g. infection.

Amino Acid Sequence↗

Massive myocardial calcification of right and left ventricles following acute myocarditis complicated with rhabdomyolysis-induced acute renal failure.

A 26-year-old man was admitted with a high fever, oliguria, skeletal muscle weakness, and cardiogenic shock which led to a diagnosis of acute myocarditis and acute rhabdomyolysis. During treatment with hemodialysis and calcium supplementation, because of severe hypocalcemia, a massive calcification of both right and left ventricular myocardium gradually became apparent with repeated computed tomographic (CT) examinations. Technetium-99m scannings more clearly delineated the markedly accumulated calcium in the myocardium, while significant activity was not detected in other soft tissues. Histopathological examinations by myocardial biopsy revealed a large amount of fibrosis and calcium deposits, and serial CT scans showed a gradual regression of the calcium deposition, suggesting that this rare form of massive dystrophic calcification may parallel changes in the severity of myocarditis, and may be associated with abnormalities in calcium metabolism secondary to rhabdomyolysis-induced acute renal failure.

Acute Disease↗

Transgenic mice with antisense RNA against the nucleocapsid protein mRNA of mouse hepatitis virus.

In this study transgenic mice which expressed antisense RNA against the nucleocapsid protein gene of mouse hepatitis virus (MHV) under the control of RSV LTR were produced. These transgenic mice were able to transmit the foreign gene to their progeny in a Mendelian fashion. Antisense RNA was detected in various tissues from the transgenic mice including liver and brain, the target organs of MHV infection. One strain of transgenic mice derived from founder mouse No. 19 was more resistant to the lethal challenge of MHV than non-transgenic mice. The results of the present study show the ability of antisense RNA against the viral gene to protect against viral infection in vivo.

Animals↗

[Clinical studies on imipenem/cilastatin sodium in the field of obstetrics and gynecology].

The efficacy and safety of imipenem/cilastatin sodium (IPM/CS) were studied in patients with obstetric and gynecologic infections and in those given the drug as prophylaxis against postoperative infections. The following results were obtained: 1. Efficacy rates were 96.0% (48/50) in patients with obstetric and gynecologic infections and 100% (28/28) in those with urinary tract or other infections. The overall efficacy rate was 97.4% (76/78). Bacteriologically, 30 organisms were isolated from 28 patients. The eradication rate was 95.2% (20/21) and the efficacy rate was 96.4% (27/28). 2. Changes in blood elastase before and after treatment were compared with those in CRP, WBC, and ESR in the patients with obstetric and gynecologic infections. The changes in elastase were similar to those in CRP. 3. The efficacy rate was 98.0% (48/49) in the patients given prophylaxis against postoperative obstetric and gynecologic infections. 4. An adverse reaction was observed in only one patient (diarrhea), and abnormal laboratory findings were noted in 2 patients (elevation of GOT and GPT). These results indicate that IPM/CS is very useful for the treatment of obstetric and gynecologic infections.

Adolescent↗

Immunological analysis and characterization of lymphocyte subsets in specimens of human hepatocellular carcinomas and metastatic liver cancers.

The distribution and number of CD2 (Coulter T11)+ cells, CD16 (Leu 11b)+ cells, Leu 7+ cells, CD8 (OKT 8)+ cells, CD11 (Leu 15)+ cells, CD4 (Leu 3a + 3b)+ cells and Leu 10+ or Leu 14+ cells in the liver of patients with hepatocellular carcinoma (HCC) and metastatic liver cancer (MLC) were investigated using monoclonal antibodies and immunohistological methods. In the majority of those with HCC and MLC, CD8 (OKT 8)+, Leu 7+ and CD16 (Leu 11b)+ cells were present both in the tumor and non-tumor tissues. The CD8 (OKT 8)+ cells were more numerous than Leu 7+ and CD16 (Leu 11b)+ cells. No significant difference was observed in the distribution and number of Leu 7+ and CD16 (Leu 11b)+ cells, in any area, in both groups. The number of CD8 (OKT 8)+ cells predominated in the non-tumor area, in both groups. CD11 (Leu 15)+ cells and CD8 (OKT 8)+ cells were present in the ratio of 1:3 or 1:4. The number of CD4 (Leu 3a + 3b)+ cells was less than that of CD8 (OKT 8)+ cells in both groups, especially in the tumor area. A few Leu 10+ or Leu 14+ cells were present in all areas, in both groups. In most cases of MLC, the CD8 (OKT 8)+ cells were absent in the tumor area. There was no correlation between the distribution and number of these cells and anti-tumor chemotherapy or non-specific immunotherapy.

Animals↗

Overexpression and purification of the recombinant Ca2+-binding protein, apoaequorin.

The small, monomeric Ca2+-binding photoprotein, aequorin, emits blue light by an intramolecular reaction when mixed with Ca2+. The photoprotein is made up of coelenterazine and molecular oxygen, bound noncovalently to apoaequorin (apoprotein). The chemical steps leading to light emission, involving the oxidative degradation of coelenterazine, have been studied extensively, but little is known about the active site and how the molecule catalyzes the oxidation of coelenterazine. The three-dimensional structure of the protein has not been determined and therefore answers to these questions have remained unavailable. The present paper describes a procedure for preparing fairly large amounts of apoaequorin and aequorin for X-ray crystallographic studies. It consists of fusing the apoaequorin cDNA to the signal peptide coding sequence of the outer membrane protein A of Escherichia coli, which is under the control of the lipoprotein promoter. When the cDNA was expressed in E. coli, a large excess of the recombinant protein was produced and released into the culture medium. Purification of the protein was accomplished by acid precipitation and DEAE-cellulose chromatography. The procedure yielded 7.4 mg of recombinant apoaequorin with a purity greater than 95% from 200 ml of culture medium. On regeneration with coelenterazine, the recombinant aequorin was fully active with Ca2+.

Aequorin↗

[Effect of soft laser on pain].

Two kinds of semiconductor laser, STOMA-LASER and Four-Luck, were used for patients having pain in the mouth and their effective rates were compared in 93 patients (133 cases). As a result, the following results were obtained. 1. The effective rate was 70.7% at the stage just after radiation. 2. Age, sex and oral hygiene were not significant for the effective rate. 3. The kinds of diseases were remarkably significant. 4. The kind of apparatus did not play any role in the effective rate as a whole, but was significant for the kinds of disease.

Facial Pain↗

[Chemotherapy of chronic myelogenous leukemia--VP(M) regimen initiated during its chronic phase, and evaluation of MCNU in the phase of blastic crisis].

Seventy-four patients in the chronic phase of Ph1-positive chronic myelogenous leukemia (CML) have been treated with busulfan or other alkylating agents in a conventional way. During its chronic phase, 24 of these 74 cases had received additional intermittent therapy every 4 to 6 months, consisting of vincristine 2 mg or vindesine 3 mg per week, prednisolone 20-30 mg per day and partly 6 mercaptopurine 50 to 100 mg, combined with allopurinol 200 to 300 mg per day for 2 to 3 weeks. The 50% survival of these patients using the Kaplan-Meier's method was 73.7 months and 5-year survival was 69.6%, against 40.5 months and 14.4%, respectively, in the remaining patients. Nine patients in the blastic or accelerated phase of Ph1-positive CML have been treated with new regimens including MCNU. All cases had been refractory for usual types of induction chemotherapy. The new regimen consisted of MCNU 50-100 mg, combined with vindesine or 6-MP plus allopurinol or prednisolone. Five out of 9 cases attained complete remission and 1 partial remission. The major adverse effect of this regimen was slight liver damage. MCNU could be regarded as an useful agent in the blastic phase as well as in the chronic phase of CML.

Adolescent↗