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Biomedical subjects

T Ando

Publications and source records attributed to T Ando.

At least 217 records · Page 12Linked to original sources

COUP-TFI expression in human adrenocortical adenomas: possible role in steroidogenesis.

Chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI) is an orphan nuclear receptor essential for neurogenesis, organogenesis, and cell fate determination. CYP17 gene transcription has recently been shown to be activated by SF-1 (steroidogenic factor-1) binding to a cyclic AMP-responsive sequence within the promoter region of the gene, and inhibited by COUP-TF binding to the sequence. Thus, COUP-TF and SF-1 act as a transcriptional repressor and activator, respectively, of CYP17 gene expression. Transcriptional repression by COUP-TFI is mediated by corepressors, N-CoR (nuclear receptor-corepressor) and SMRT (silencing mediator for retinoid and thyroid hormone-receptor), whereas transcriptional activation by SF-1 is mediated by coactivator SRC-1 (steroid receptor coactivator-1). We therefore examined the expression of COUP-TFI, SF-1, SRC-1, N-CoR, and SMRT in a variety of adrenocortical adenomas and compared the results with CYP17 mRNA levels. We found significantly high COUP-TFI mRNA expression in nonfunctional adenomas (n=8: 220+/-16%; normal 96+/-4%), a deoxycorticosterone-producing adenoma (n=1: 200%), and a pre-clinical Cushing's adenoma (n=1: 280%), intermediate COUP-TFI expression in cortisol-producing adenomas (n=8: 63+/-5%), and low COUP-TFI expression in aldosterone-producing adenomas (n=8: 49+/-4%). In contrast to COUP-TFI, SF-1 mRNA expression did not vary significantly among adrenals. We did not detect the expected negative correlation between COUP-TFI and CYP17 mRNA levels in adrenocortical adenomas. High COUP-TFI expression was associatedwith a nonfunctioning phenotype. Interestingly, the pattern of COUP-TFI expression was similar to the profile of N-CoR expression, but not of SMRT expression. These results indicate that COUP-TFI and N-CoR may play a role in steroidogenesis by human adrenocortical adenomas.

Adenoma↗

Nasal insulin delivery in rabbits using soybean-derived sterylglucoside and sterol mixtures as novel enhancers in suspension dosage forms.

The effect of a soybean-derived sterol mixture (SS) and a steryl glucoside mixture (SG) as enhancers of the nasal absorption of insulin in rabbits was investigated. SS consists of beta-sitosterol (Sit), campesterol (Camp), stigmasterol (Stig) and brassicasterol (Bras), and SG is a mixture of their monoglucosides. For each component of SS tested for efficacy in promoting the systemic absorption of nasally administered insulin, the following order was observed: Sit> or =Camp>Stig. This finding was in agreement with the order of the enhancers' lipophilicity. In the case of SG, the effect of beta-sitosterol beta-D-glucoside (Sit-G) was significantly greater than that of SG. The pharmacological bioavailability was 6.7% for SG and 11.3% for Sit-G in the suspension dosage forms. SG showed a greater degree of enhancement of insulin permeation through the nasal mucosa than SS. To elucidate the contribution of SG to the enhanced absorption, insulin permeation through an artificial membrane and the nasal mucosa was investigated in vitro, and the results were compared with those for SS. The findings suggest that SG and SS have some effect on nasal mucosa lipids.

Absorption↗

High absorbency and subchronic morphologic effects on the nasal epithelium of a nasal insulin powder dosage form with a soybean-derived sterylglucoside mixture in rabbits.

A soybean-derived sterylglucoside mixture (SG) is a potential enhancer of the nasal absorption of insulin. The aim of the study was to examine the absorption of insulin given as the powder dosage form with SG and excipient and to determine the subchronic effects of SG on the morphology of rabbit nasal epithelium. The insulin powder dosage form with SG was administered to the rabbit nasal cavity for five successive days. The average bioavailability and the average pharmacological bioavailability of insulin were about 25.0 and 61.6%, respectively. The nasal mucosa was taken from the nasal cavity and side-effects were investigated using an optiphoto light microscope. The insulin powder dosage form with SG produced no signs of inflammation, erosion or squamous metaplasia. These findings indicate that SG can be considered as a safe and effective enhancer and excipient in the nasal insulin powder dosage form.

Absorption↗

Aqueous humor dynamics in beagle dogs with caffeine-induced ocular hypertension.

In order to investigate the possible mechanisms for caffeine-induced ocular hypertension, the intraocular pressure (IOP) and the outflow through the trabecular meshwork were measured in beagle dog eyes after dosing with intravenous caffeine (30 mg/kg) alone or in combination with the topical beta-blocker befunolol [applied as 100 microliters of a 1% (w/v) solution] which inhibits aqueous humor formation in the ciliary body. Intravenous injections of caffeine significantly increased the IOP at 0.25 and 1 hr after a single dose. The ocular hypertension recovered within 2 hr following dosing. Over time, there were no differences in the outflow between the caffeine and control groups. The instillation of befunolol lowered outflow and produced ocular hypotension. The levels of the IOP and outflow in dogs treated with caffeine and befunolol in combination were almost the same as those in dogs treated with befunolol alone. Single-dose and combination-dose studies demonstrate that intravenous caffeine increases the IOP in normal beagle dogs possibly by increasing aqueous humor formation and not by the inhibition of aqueous humor drainage through the trabecular meshwork.

Adrenergic beta-Antagonists↗

The protective effect of a persistent trigeminal artery on brain stem infarctions: a follow-up case report.

A persistent trigeminal artery (PTA) represents an embryonic vascular anastomosis connecting the carotid and basilar arterial systems. Little is known about its protective role in cases of basilar artery occlusion. We followed up a 63-year-old man who had suffered a brain stem infarction due to basilar artery stenosis and was found to have a PTA. Although a second brain stem infarction due to basilar artery occlusion developed, the circulation to the brain stem was well maintained via collateral flow from the PTA, and the patient demonstrated good recovery. A PTA may function as an anastomosis between the carotid and basilar systems, thus preventing a more serious infarction.

Arteriosclerosis↗

Isolation and characterization of a new pyrano[4',3':6,7]naphtho[1,2-b]xanthene antibiotic FD-594.

During our screening of microbial metabolites for effective drugs against tumor cell lines, we discovered a new pyrano[4',3':6,7]naphtho[1,2-b]xanthene derivative, FD-594 from the fermentation broth of Streptomyces sp. TA-0256. FD-594 shows moderate activity against tumor cell lines, comparative to that of adriamycin, as well as antibacterial activity against some Gram-positive bacteria.

Animals↗

A novel bone resorption inhibitor, A-75943 isolated from Streptomyces sp. SANK 61296.

A novel bone resorption inhibitor, A-75943, was isolated from Streptomyces sp. SANK 61296. Its structure was determined to be (1"S,2'R,3"S,4S',5"S)-2-[(3",5"- dimethyl-2"-oxocyclohexan-1"-yl)-6'-oxotetrahydropyran-4'-yl ]acetamide by spectral analyses and chemical conversion of cycloheximide. A-75943 inhibited bone resorption in vitro in a concentration-dependent manner with an IC50 of 0.35 microM, and also displayed an inhibitory effect on bone resorption in thyroid and parathyroid-extracted rats.

Animals↗

Variation of the total amount of fluoride in blood of young women during the menstrual cycle.

We have previously reported the distribution and the forms of fluorides in the blood of men. This study is concerned with the distribution of fluorides in the blood of young women and sex-related differences in the fluoride metabolism related to the calcium metabolism keeping the postmenopausal osteoporosis in mind. The present study shows that women, aged 18 to 20 years, retain more fluorides in blood compared with men and that the nonionic fluoride level in blood varies during a menstrual cycle, whereas the ionic fluoride level is constant. Since fluoride has strong affinity for calcium, behavior of fluoride may reflect that of calcium balance during the menstrual cycle. However, fluoride which binds to calcium is believed to be ionic. Therefore, there must be a transformation between ionic fluoride and nonionic fluoride in order to keep the homeostasis.

Adult↗

[A welder with chemical pneumonitis caused by inhalation of zinc fume].

A 61-year-old man with a 32-year occupational history of welding developed malaise, cough, and dyspnea after inhalation of smoke while welding galvanized steel. On admission, peripheral leukocytosis, hypoxemia, and diffuse granular and linear opacities on a chest X-ray were present. The bronchioli were exaggerated in a chest high-resolution CT. Bronchoalveolar lavage revealed mild lymphocytosis and transbronchial lung biopsy showed siderosis and exudation of fibrin and neutrophils into alveolar spaces. The clinical and radiographic findings later improved except for an obstructive disorder on pulmonary function test. The respiratory health hazards associated with welding vary according to the materials and the concentration of inhaled substances. Acute chemical pneumonitis caused by inhalation of zinc fumes (zinc oxide) was accompanied by chronic siderosis in this case. It is well known that metal fume fever commonly occurs when inhaling zinc oxide fumes. However acute chemical pneumonitis after exposure to zinc oxide during welding has been only rarely reported.

Aerosols↗

In vivo comparison of PET and SPECT radiopharmaceuticals in detecting breast cancer.

UNLABELLED: Various radiopharmaceuticals for breast cancer detection have been used for scintimammography and PET. However, few comparative studies have described the uptake of radiopharmaceuticals as a method of detecting breast cancer. The aim of this study was to assess the radiopharmaceuticals for breast cancer imaging in experimental mice implanted with breast cancer cells. METHODS: Six radiopharmaceuticals were studied: three for PET [18F-fluorodeoxyglucose (FDG), L-18F-alpha-methyltyrosine (FMT) and 11C-methionine (C-Met)] and three for scintimammography [99mTc-tetrofosmin (TF), 99mTc-sestamibi (MIBI) and 201Tl-chloride (Tl)]. Biodistributions of six different tracers in mice implanted with MCF-7 breast cancer cells were studied 1 and 3 hr after injection. RESULTS: Tumor uptake 1 hr after injection was FMT = C-Met > FDG = TF > MIBI = Tl. Thallium-201-chloride showed the highest tumor-to-blood ratio (T/B) among all radiopharmaceuticals because of its fast clearance from circulation. The T/B of the six radionuclides used in this study ranged from 1.26 for C-Met to 12.83 for Tl. Tumor-to-muscle ratio (T/M) revealed FMT = C-Met > FDG > MIBI > TF = Tl. The T/M ranged from 0.20 for TF to 2.29 for FMT. Tumor-to-lung ratio (T/L) varied from 0.45 for TF to 2.41 for FMT. FMT revealed the highest T/L of all six radiopharmaceuticals. CONCLUSION: Among radiopharmaceuticals for PET, FMT seemed to be suitable in detecting MCF-7 tumor; whereas for scintimammography, MIBI, TF and Tl appeared to have almost the same detectability of MCF-7 tumor. The results of this study strongly suggest that FMT may have a potential in breast cancer imaging.

Animals↗

[Analysis of air pollution and prevalence rate of allergic diseases among elementary school children in Kawaguchi and Hatogaya city].

Kawaguchi and Hatogaya City are located on the northern edge of Tokyo. We analysed between air pollution and prevalence rate of allergic diseases among elementary school children in this area. A prevalence rate of allergic diseases in 1996 May and June was as follows; bronchial asthma 13.5%, atopic dermatitis 24.5%, allergic rhinitis and/or conjunctivitis 22.8%, urticaria 12.4%, food allergy 7.8% and drug allergy 2.2%, respectively. Air pollution of this area was analysed to check the levels of nitrogen dioxide (NO2), sulfur dioxide (SO2) and suspended particulate matters (SPM). NO2 pollution was relatively high in urban area, and SPM pollution was especially high around the highways. SO2 pollution was lower than the environmental standard. No relationship was found between the prevalence rate of bronchial asthma, atopic dermatitis, allergic rhinitis and/or conjunctivitis and air pollution, but it was found that these diseases are slightly related to population density (p < 0.1, p < 0.01, p < 0.1, respectively).

Air Pollutants↗

DNA cleavage reaction and linoleic acid peroxidation induced by tea catechins in the presence of cupric ion.

Tea catechins with cupric ion promoted extensive DNA cleavage and fatty acid peroxidation in vitro under aerobic conditions. Neither cupric ions nor polyphenolic compounds including catechins alone induced DNA cleavage. While catalase significantly inhibited the DNA cleavage induced by catechins-Cu2+, superoxide dismutase (SOD) did not, indicating that H2O2 is probably involved in the DNA cleavage. These results suggest that the pro-oxidant property of catechins, which are generally considered to be anti-oxidants and anticarcinogens, is responsible for the O2 reducing ability of catechins catalyzed by cupric ion.

Aerobiosis↗

Outbreak of viral gastroenteritis due to a contaminated well. International consequences.

CONTEXT: Small round-structured viruses (SRSVs) are known to cause viral gastroenteritis, but until now have not been confirmed in the implicated vehicle in outbreaks. OBJECTIVE: Investigation of a gastroenteritis outbreak. DESIGN: After applying epidemiologic methods to locate the outbreak source, we conducted environmental and laboratory investigations to elucidate the cause. SETTING: Tourists traveling by bus through Alaska and the Yukon Territory of Canada. PARTICIPANTS: Staff of a restaurant at a business complex implicated as the outbreak source, convenience sample of persons on buses that had stopped there, and bus employees. MAIN OUTCOME MEASURES: Odds ratios (ORs) for illness associated with exposures. Water samples from the restaurant and stool specimens from tourists and restaurant staff were examined by nucleic acid amplification using reverse transcription polymerase chain reaction and sequencing of viral amplification products. RESULTS: The itineraries of groups of tourists manifesting vomiting or diarrhea were traced back to a restaurant where buses had stopped 33 to 36 hours previously. Water consumption was associated with illness (OR, 5.3; 95% confidence interval [CI], 2.3-12.6). Eighteen of 26 employees of the business complex were ill; although not the index case, an employee ill shortly before the outbreak lived in a building connected to a septic pit, which was found to contaminate the well supplying the restaurant's water. Genotype 2/P2B SRSV was identified in stool specimens of 2 tourists and 1 restaurant employee. Stools and water samples yielded identical amplification product sequences. CONCLUSIONS: The investigation documented SRSVs in a vehicle epidemiologically linked to a gastroenteritis outbreak. The findings demonstrate the power of molecular detection and identification and underscore the importance of fundamental public health practices such as restaurant inspection, assurance of a safe water supply, and disease surveillance.

Base Sequence↗

Hepatoprotective effect of a nonselective endothelin receptor antagonist (TAK-044) in the transplanted liver.

This study was designed to investigate whether or not a novel nonselective endothelin A/B (ETA/ETB) receptor antagonist (TAK-044) provides hepatoprotection during porcine liver transplantation. The grafts were stored in chilled Euro-Collins solution and recirculated following reflush with lactated Ringer's with (TAK group) or without (control group) TAK-044 (10 mg/kg). Intracellular (cytoplasma, mitochondria, and nucleus) calcium (Ca) concentrations were measured in the hepatic biopsy materials obtained serially at varying time point from donor laparotomy to recipient closure using an electron probe X-ray microanalyzer. Liver function tests also were determined. The cold and warm ischemia times of the grafts were comparable between the two groups. The peak endothelin-1 T-1) concentration after recirculation was significantly higher in the TAK group than in the control group (129 +/- 30 pg/ml vs 26 +/- 6.5 pg/ml). However, release of liver enzymes, increases in total bile acid, and deterioration of indocyanine green retention rate were significantly suppressed in the TAK group. In the control group, the intracellular Ca concentrations, especially in the mitochondrial fraction, were elevated markedly following recirculation of the hepatic arterial flow. In the TAK group, this effect was suppressed. Thus, the supplementary use of the nonselective ETA/ETB receptor antagonist TAK-044 via a rinse route may alleviate an early postreperfusion microcirculatory disturbance of the liver grafts without adverse effects by the increased ET-1 on the systemic circulation.

Animals↗

Inhibitory effects of pituitary adenylate cyclase activating polypeptide on histamine-induced respiratory resistance in anesthetized guinea pigs.

Asthma is a chronic inflammatory disorder of the airways in which many cells participate. This inflammation causes recurrent episodes and symptoms that are associated with widespread but variable airflow limitation that is at least partly reversible either spontaneously or with treatment. Therefore, an investigation of useful remedies for the treatment of bronchial asthma is proposed. In this study, we determined whether both forms of pituitary adenylate cyclase activating polypeptide (PACAP 38 and PACAP 27) belonging to the vasoactive intestinal peptide (VIP) family of peptides could inhibit the effects of histamine-induced respiratory resistance (Rr) in anesthetized guinea pigs, when compared with VIP. The order for 50% suppression (ED50) of Rr induced by peptides was VIP > PACAP 27 > PACAP 38. The inhibitory effects induced by PACAP 38 on histamine-induced Rr in guinea pigs were more prolonged than with the other two peptides. Moreover, adding the endopeptidase inhibitor phosphoramidon prolonged the inhibitory effects of PACAPs. These results suggested that the exogenous peptides of the inhibitory nonadrenergic noncholinergic nervous (i-NANC) peptides could become a useful remedy for treatment of bronchial asthma, because these belong to an important intrinsic hormone.

Airway Resistance↗

Scanning force microscopy of the interaction events between a single molecule of heavy meromyosin and actin.

How close an approach is necessary for two interactive protein molecules to recognize each other before association? How strong a force field is exerted between two proteins at the recognition distance? How extensive are the association interfaces? How strong a force is necessary to pull the associated proteins apart? By means of atomic force microscopy at a truly single molecule level, these fundamental and intriguing questions were answered with the muscle proteins actin and myosin.

Actins↗