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Biomedical subjects

A Mizuno

Publications and source records attributed to A Mizuno.

At least 127 records · Page 7Linked to original sources

Is caloric restriction effective in preventing diabetes mellitus in the Otsuka Long Evans Tokushima fatty rat, a model of spontaneous non-insulin-dependent diabetes mellitus?

Studies were made on the effectiveness of caloric restriction in preventing the development of diabetes mellitus in a model rat (Otsuka-Long-Evans-Tokushima Fatty; OLETF) with non-insulin-dependent diabetes mellitus (NIDDM). Groups of 8 male OLETF rats aged 5 weeks were supplied with rat chow ad libitum (100% group) and 85% and 70% of the amount of food consumed by the 100% group (85% and 70% groups, respectively). The average weights of the 100%, 85% and 70% groups were 617, 536 and 450 g at 19 weeks of age and their abdominal fat deposits were 50, 38 and 21 g, respectively, at 22 weeks of age when they were killed. At 20 weeks of age, the cumulative incidences of diabetes mellitus in the 100%, 85% and 70% groups were 67%, 13% and zero, respectively. The plasma immunoreactive insulin (IRI) levels 60 and 120 min after oral glucose administration were significantly lower in the 70% group than in the other groups. In vivo insulin-stimulated glucose uptake measured by a euglycemic clamp technique, was significantly higher in the 70% group than in the 100% group. There was no significant difference in the glucose transporter 4 protein levels of skeletal muscles in the three groups, but the highest ratio of glucose transporter 4 in the plasma membrane to that in intracellular membranes was observed in the 70% group. Morphological studies on the pancreas of rats in the 100% group showed enlarged multilobulated fibrotic islets, whereas sections of islets of rats in the other groups appeared normal, though slightly enlarged. These results demonstrate that caloric restriction is effective in preventing NIDDM in diabetes-prone rats, probably due to increased insulin sensitivity.

Aging↗

Effects of obesity and inheritance on the development of non-insulin-dependent diabetes mellitus in Otsuka-Long-Evans-Tokushima fatty rats.

We studied whether obesity or inheritance was the more important factor in the development of non-insulin-dependent diabetes mellitus (NIDDM) using female Otsuka-Long-Evans-Tokushima Fatty rats (OLETF) possessing one of the diabetic genes, ODB-1, and male Long-Evans-Tokushima-Otsuka rats (LETO) possessing no ODB-1, neither of which were diabetic when bred normally. Diabetes-resistant male LETO rats and female OLETF rats (4 weeks old) were assigned to three groups of 6 rats each, respectively; two groups in which obesity was induced by high calorie 'cafeteria' diet (D), or ventromedial hypothalamus lesions (V) with normal chow diet and a control group fed on normal chow (C). Six male OLETF rats were used as NIDDM positive controls. The mean daily energy intakes of obese male LETO and female OLETF rats were higher than those of the respective C groups. At 27 weeks of age, the average body weights of the obese LETO and female OLETF rats were significantly higher than those of the respective C groups and similar to that of the male OLETF group. Abdominal fat deposits of the obese groups were significantly higher than those of the respective C groups. At 28 weeks of age, the cumulative incidence of diabetes mellitus in obese LETO rats was 0% in group D and 17% in group V, while that of obese female OLETF rats in groups D and V were 100%. At 29 weeks of age, the plasma immunoreactive insulin (IRI) responses to glucose in obese female OLETF rats, groups D and V, were higher than that in group C. In obese LETO rats, insulin-stimulated glucose disposal in vivo was similar to that in group C, but in obese female OLETF rats, it was reduced to 41% in group D and 37% in group V of that in group C. Sections of islets of the pancreas of obese LETO rats appeared histologically normal, whereas those of obese female OLETF rats showed enlarged multilobulated fibrotic islets. These results demonstrate that obesity is necessary, but not sufficient alone for the development of NIDDM in these rat models.

Analysis of Variance↗

Effect of timely insulin administration on pancreatic B-cells of Otsuka-Long-Evans-Tokushima-Fatty (OLETF) strain rats. An animal model of non-insulin dependent diabetes mellitus (NIDDM).

Morphological changes of the pancreas and impairment of pancreatic B-cell function in a model rat (Otsuka Long Evans Tokushima Fatty [OLETF]) with non-insulin dependent diabetes mellitus might be the result of over-activity of B-cells to compensate for insulin insensitivity. To test this possibility, we studied whether the histological and functional alterations in the pancreas of male OLETF rats were improved by treatment with insulin for a certain period, which might reduce the burden to B-cells. Groups of 6 male OLETF rats and 5 or 4 male non-diabetic control Long Evans Tokushima Otsuka (LETO) rats received injections of insulin (Ultralente MC; 10 U/kg/day to OLETF rats, 5 U/kg/day to LETO rats) or saline subcutaneously, once a day for 3 weeks from 24 weeks of age. Then their insulin responses to glucose (200 mg/dl) and arginine (10 mmol/l) were examined by perfusion of the pancreas. The morphological features of their pancreata were also examined. The insulin response to glucose in OLETF rats treated with insulin was significantly higher than that of OLETF rats treated with saline (sigma IRI 142.5 +/- 27.0 vs. 37.4 +/- 6.3 ng/ml.20 min, p < 0.05) and unlike in the latter showed the normal two phases. The morphological changes of the pancreas in the insulin-treated OLETF rats were remarkably ameliorated, animals showing no enlargement and only slight fibrosis of islets. Thus treatment with insulin was effective for preventing B-cell dysfunction and morphological changes of the pancreas in NIDDM model rats.

Animals↗

Construction of human immunodeficiency virus 1/simian immunodeficiency virus strain mac chimeric viruses having vpr and/or nef of different parental origins and their in vitro and in vivo replication.

We constructed a series of human immunodeficiency virus 1 (HIV-1)/simian immunodeficiency virus strain mac (SIVmac) chimeric viruses having vpr and/or nef genes of either HIV-1 or SIVmac based on a chimeric virus with LTRs, gag, pol, vif and vpx derived from SIVmac and tar, rev, vpu and env from HIV-1. All of the chimeric viruses replicated in human and macaque peripheral blood mononuclear cells (PBMCs) and in several CD4+ human cell lines, though their growth potentials were slightly different depending on whether vpr and nef were from HIV-1 or SIVmac, or were defective. The presence of nef accelerated replication in all the cells used and the replication of each chimera appeared to reflect that of the parental virus from which nef was derived. The presence of vpr had no clear effect in human and monkey PBMCs, but the replication of each chimera was influenced by the origin of vpr in H9 and A3.01 cells. NM-3rN, which carries HIV-1 vpr and SIVmac nef, was inoculated intravenously into three rhesus monkeys, three cynomolgus monkeys and two pig-tailed monkeys. From 2 to 14 weeks after inoculation, viruses were consistently re-isolated from all the monkeys and virus loads were as high as that of SIVmac reported previously. The results indicate that infection with NM-3rN is more efficient than any of our previous chimeric viruses and suggest that NM-3rN, having HIV-1 Env, will be a useful challenge virus for evaluating AIDS vaccines based on HIV-1 Env in macaque monkeys instead of chimpanzees.

Animals↗

Differential transcription of the MPB70 genes in two major groups of Mycobacterium bovis BCG substrains.

Substrains of Mycobacterium bovis BCG (BCG) have been divided into two major groups, high and low producers, on the basis of the amount of secretion of the MPB70 protein. The antigen is produced in high concentration by BCG Tokyo, Moreau, Russia and Sweden (high-producer substrains), whereas in BCG Pasteur, Copenhagen and Tice (low-producer substrains) it is detected at 1% (w/w) or less of the concentration of BCG Tokyo. To investigate why this protein is secreted differently, the MPB70 genes of BCG Tokyo and Pasteur were cloned, sequenced and compared. The MPB70 genes in two substrains showed exactly the same sequence. Even the upstream and downstream regions of the MPB70 gene were identical. MPB70 gene expression was assessed by means of Northern hybridization analysis and reverse transcriptase polymerase chain reaction. The mRNA was clearly detected in BCG Tokyo, but a very low level in BCG Pasteur. On the basis of these results, the difference in the secretion of the MPB70 protein between BCG Tokyo and Pasteur was attributed to differential transcription efficiencies.

Amino Acid Sequence↗

The axial distribution of nicotine content along hair shaft as an indicator of changes in smoking behaviour: evaluation in a smoking-cessation programme with or without the aid of nicotine chewing gum.

1. Hair samples were obtained from subjects at the end of a 6 month smoking-cessation programme carried out with (n = 16) or without (n = 10) the aid of nicotine chewing gum. The axial distribution of nicotine along the hair shaft was determined and compared both with the self-report of smoking behavior and with the concentration of carbon monoxide (CO) in expired air measured at 1 month intervals. 2. A gradual decrease in nicotine content along the hair shaft corresponded to the decrease in self-reported number of cigarettes smoked daily in both the nicotine chewing-gum treated and untreated subjects and with the clinical assessment of abstinence. 3. There was reasonable agreement between the CO content of expired air, the self-reported number of cigarettes smoked daily and the axial distribution of nicotine in 22 of 26 subjects. In the other four subjects there was an apparent disagreement between the CO content of expired air and the other parameters. 4. This study showed that, as a routine marker of smoking status, hair analysis may be preferable to repeated CO measurements since only a single sample at the end of an abstinence programme might be sufficient. However, one problem is that nicotine may dissociate slowly from melanin to limit the ability to mark a sudden cessation of smoking. Also, some nicotine in hair might be attributable to nicotine adsorbed to the outside of hair.

Adult↗

Synovial chondromatosis of the temporomandibular joint.

A case of synovial chondromatosis of the temporomandibular joint in a 48-year-old woman is presented. Computed tomography and magnetic resonance imaging contributed to a clear understanding of the extent of the lesion and were helpful in both surgical treatment planning and follow-up.

Chondromatosis, Synovial↗

[Surgical treatment of infective endocarditis: application of DNA probe method].

DNA probe method is a new bacteriological method for diagnosis of bacteria. The authors tried to apply the method to diagnosis of bacteremia and treatment of infective endocarditis. We could diagnose the patient's illness as bacteremia with this method even when blood cultures are not positive. We suggest that cardiac surgery should be performed in case bacteria is detected repeatedly with DNA probe method. Therefore it is useful for decision whether cardiac surgery for patients with active infective endocarditis should be done or not.

Adolescent↗

[Successful treatment of aortic prosthetic valve endocarditis and aortic root abscess by Bentall procedure].

A 53-year-old woman had undergone aortic valve replacement in 1990. Three years later, aortic prosthetic valve endocarditis and aortic root abscess had been noted. Debridement of all apparently infected tissue created left ventricular-aortic discontinuity, but the orifice of the coronary arteries were intact. We decided to reconstruct the left ventricular outflow tract and aortic root by Bentall procedure. Composite graft was made with 26 mm gelseal tube graft and a 23 mm SJM prosthetic valve, and the coronary ostia were sutured into the side of the graft. The patient's recovery was uneventful, and the aortography revealed no aortic regurgitation. We suggest that Bentall procedure using gelseal tube graft is useful to reconstruct the left ventrivular-aortic discontinuity if the coronary ostia were intact.

Abscess↗

[Direct implantation of the left coronary artery in BWG syndrome--sparing the shortage of distance with pulmonary arterial wall].

Anomalous origin of the left coronary artery (ALCA) arising from the pulmonary artery is a rare anomary, and causes myocardial infarction and death in children. Direct implantation of ALCA to the aorta was performed in the 6-year-old female patient. A large button of pulmonary arterial wall resected with ALCA could spare the shortage of the distance between the aorta and the ALCA. Postoperative catheterization displayed non-stenotic left coronary artery. Left ventricular function assessed by echocardiography showed improvement. Cold area in early stage postoperative myocardial imaging disappeared one year after the surgery, which suggested the hibernation of the preoperative myocardium.

Aorta↗

Alteration of lens sulfhydryl groups induced by oxidative stress: Raman spectroscopic study of hydrogen peroxide-treated rat lens.

It has been reported that hydrogen peroxide is present in the aqueous humor and its level is increased in cataract patients. To determine the effect of hydrogen peroxide on the lens, hydrogen peroxide-treated lenses were monitored by Raman spectroscopic methods before and after treatment. The lenses were also examined histologically. Excised rat lenses were incubated in the medium containing 100 mM of hydrogen peroxide for one hour. Slight lens opacification was observed 3 hours after completion of treatment and there was marked opacification by 5 hours. Analysis of the Raman spectra from the lens cortex indicated that sulfhydryl groups were decreased and disulfide bonds were increased, which suggested that exposure to hydrogen peroxide resulted in 2SH --> SS conversion in the lenses. A decrease in sulfhydryl groups was observed at one hour after completion of treatment and its level was decreased to 60% of the control level by 4 hours after treatment. Since the decrease in sulfhydryl groups was observed prior to lens opacification, the results indicated that 2SH --> SS conversion may be related to the formation of lens opacification.

Animals↗

Cell-specific translational control of transcription factor BTEB expression. The role of an upstream AUG in the 5'-untranslated region.

BTEB is a GC-box binding transcription factor that can activate human immunodeficiency virus type 1 long terminal repeat and cellular gene promoters containing multiple GC boxes. The present studies showed that although BTEB mRNA was expressed in various tissues of mammals and cell lines, the expression of BTEB protein was confined to the brain and a neuroblastoma Neuro2A (N2A), suggesting that the BTEB expression was translationally regulated in a cell-specific or tissue-specific manner. The BTEB mRNA was characterized by a long (1.26 kilobases( 5'-untranslated region (5'-UTR) containing 10 upstream AUGs (uAUGs) and a GC-rich tract. To examine whether the 5'-UTR controlled the translation in a cell-specific manner, a fusion plasmid composed of the BTEB 5'-UTR and the chloramphenicol acetyltransferase gene was transfected into HeLa and N2A cells. Translational efficiency of the transcribed mRNA was estimated from the chloramphenicol acetyltransferase activity normalized on the basis of the amount of the mRNA. The 5'-UTR was found to decrease the translational efficiency by 7-fold in HeLa cells; that in N2A was not affected. When one of the uAUGs in the 5'-UTR was mutated to AAG, the inhibition of the translation by the 5'-UTR in HeLa cells was reversed; no effect of the mutation was observed in N2A cells. These results suggest that an uAUG in the 5'-UTR of the BTEB mRNA is, at least in part, responsible for the cell-specific translational control of the BTEB expression.

Animals↗

Simultaneous determination of ofloxacin, norfloxacin and ciprofloxacin in human hair by high-performance liquid chromatography and fluorescence detection.

A high-performance liquid chromatographic method for the simultaneous determination of ofloxacin, norfloxacin and ciprofloxacin in human hair is described. A reversed-phase C18 column and a fluorescence detector with switching fluorescence wavelengths were used together with solid-phase extraction of the drugs from hair dissolved in 1 M sodium hydroxide. Reproducibility and linearity studies yielded coefficients of variation of 0.2-2.2, 1.4-3.1 and 1.5-3.4%, and correlation coefficients of 1.000, 0.999 and 0.999 within the concentration range 0.3-100 ng/ml for ofloxacin, norfloxacin and ciprofloxacin, respectively. For validation, hair samples were obtained from six subjects who had been taking one or two of the three fluoroquinolones. Assuming a hair growth-rate of 1 cm per month fluoroquinolones could be detected in the hair section(s) that had grown approximately between the dates of drug administration and hair sampling.

Adult↗

Effect of 21-aminosteroid lipid peroxidation inhibitor, U74006F, in the rat middle cerebral artery occlusion model.

The aim of this study was to evaluate the effect of 21-aminosteroid lipid peroxidation inhibitor, U74006F, on ischaemic brain tissue damage using the rat middle cerebral artery occlusion model. Under anaesthesia, the left middle cerebral artery was exposed without cutting the dura mater via a subtemporal craniotomy, under an operating microscope. Photo-illumination (wave length; 540 nm) was applied to the middle cerebral artery and then rose bengal (20 mg/kg) was administered intravenously. The middle cerebral artery was completely occluded by thrombus about 6 min after the administration of rose bengal. U74006F (1.0 mg/kg) was then injected intravenously just after the cessation of illumination. Twenty four hours after the operation, the extent of ischaemic damage was measured by magnetic resonance imaging technique. After measuring the extent of ischaemic damage, the brain was immediately removed from animals treated with or without U74006F for determination of lipid peroxidation, and the generation of free arachidonic acid in the brain. U74006F significantly (P < 0.01) reduced the size of ischaemic damage. Twenty-four hours after the operation, lipid peroxidation and the concentration of free arachidonic acid in the left hemisphere (infarction side) were significantly (P < 0.05) higher than in the right hemisphere. U74006F significantly (P < 0.05) decreased the content of lipid peroxidation products and free arachidonic acid. There was a significant (P < 0.05) correlation between the extent of ischaemic damage and the concentration of lipid peroxidation products in the left hemisphere 24 h after the operation. In conclusion, U74006F might reduce the extent of ischaemic damage by inhibiting lipid peroxidation in the brain, thus minimizing oxidative damage to neural tissues.

Animals↗

Pharmacokinetic and pharmacodynamic profiles of CS-518, a selective, long-lasting thromboxane synthase inhibitor, after single and multiple oral administration to healthy volunteers.

A selective thromboxane (TX) synthase inhibitor, CS-518, was orally administered to healthy male Japanese volunteers and the pharmacokinetic and pharmacodynamic properties were investigated. The time profile of drug concentrations in plasma was determined, and the effects of the drug on platelet aggregation in plasma induced by arachidonic acid (AA) and adenosine diphosphate (ADP) ex vivo were examined. The production of TXB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in serum during whole blood coagulation ex vivo also were examined. In the single-dose study (50, 100, and 200 mg), plasma concentrations of the drug were well fitted to a one-compartment open model with first-order absorption. The area under plasma concentration curve (AUC) and maximum plasma concentration (Cmax) showed dose-related increases, whereas the mean elimination half-lives remained rather constant (.68-.92 hour). The drug was recovered in urine by 32 to 37% and 62 to 65% as unchanged and conjugated forms (acylglucuronide), respectively, showing almost complete absorption of CS-518. The effect of food intake on the pharmacokinetics of CS-518 was determined at the dose of 100 mg. The time to reach Cmax was prolonged from .42 to 2.08 hours and the Cmax was decreased by about 66%, whereas the AUC and urinary recovery showed no significant changes. The platelet aggregation in plasma induced by AA was markedly inhibited, whereas the secondary aggregation induced by ADP was inhibited to a much less degree. Platelet aggregation by AA was almost completely inhibited 2 hours after administration of any dose and the duration for maintaining the significant inhibition tended to depend on the dose ranging from 48 to 72 hours after administration, which was much longer than expected from the plasma concentration of drug.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Imaging features of maxillary osteoblastoma and its malignant transformation.

We report two cases of osteoblastoma, one of them an unusual case in a 32-year-old woman in whom a maxillary tumor was confidently diagnosed as an osteoblastoma at the time of primary excision and subsequently transformed into an osteosarcoma 7 years after the onset of clinical symptoms. The other patient developed osteosarcoma arising in the maxilla, which was diagnosed 3 years after the primary excision and is very suggestive of malignant transformation in osteoblastoma. We present the radiological features, including computed tomographic and magnetic resonance imaging studies, of this unusual event of transformed tumor and compare imaging features of benign and dedifferentiated counterparts of this rare tumor complex.

Adult↗