[Physiological and protective actions of radicals on the blood and cardiovascular systems].
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Biomedical subjects
Publications and source records attributed to Y Ishida.
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Effects of dietary carbohydrates on triglyceride production and hepatic lipogenic enzyme activities were examined in Wistar fatty rats, an animal model of noninsulin dependent diabetes mellitus, fed fructose or glucose and were compared with those of Wistar lean rats. Carbohydrates were supplied in 10% drinking solutions for 21 days. As compared with lean rats, Wistar fatty rats were characterized by hyperglycemia, hyperinsulinemia and hypertriglyceridemia, the last of which was associated with an increased hepatic activity of fatty acid synthetase and an increased rate of triglyceride secretion from the liver to the circulation. Feeding fructose to genetically obese diabetic rats produced a threefold increase in the hepatic activity of fatty acid synthetase, a twofold increase in NADPH-generating enzymes (malic enzyme and glucose-6-phosphate dehydrogenase) and a 56% increase in the rate of triglyceride secretion, with a resultant 86% increase in plasma triglyceride concentrations. Feeding glucose produced a similar increase in the activity of NADPH-generating enzymes and triglyceride production in the fatty liver but it differed in producing no change in plasma triglyceride concentrations or hepatic fatty acid synthetase activity. Neither dietary fructose nor glucose changed glycemia or insulinemia. These results show that in genetically obese, diabetic rats feeding fructose and glucose is associated with an increase in hepatic lipogenic enzyme activities and triglyceride production, and suggest that fructose stimulates triglyceride production but impairs triglyceride removal, whereas glucose stimulates both of them.
Purines of ATP, ADP, AMP and adenosine released from rat caudal artery with and without endothelium and the isolated smooth muscle and endothelial cells were examined, in order to determine the source. Treatment of intact segments of caudal arteries with noradrenaline (10 microM) for 3 min induced a large release of ATP, ADP, AMP and adenosine. However, if the artery segments had been denuded of their endothelial lining, noradrenraline induced only a slight release of purines. Endothelial cells in primary culture prepared from caudal arteries, when exposed to noradrenaline for 3 min released large amounts of purines, whereas vascular smooth muscle cells prepared similarly and passaged endothelial cells did not release purines upon exposure to noradrenaline. These results indicate that, of smooth muscle and endothelial cells of the vascular wall, only intact endothelial cells react to alpha-adrenoceptor stimulation by releasing adenine nucleotides and adenosine.
We evaluated the effect of pioglitazone, a thiazolidinedione compound, on insulin-stimulated glucose disposal (Rd) and its efficacy on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM). Twenty NIDDM subjects (mean age 58.2+/-9.4 year, body mass index (BMI) 23.9+/-3.4 kg/ m2 (mean+/-S.D.], three with diet alone, 17 with sulfonylureas [SU]) participated in this trial from five diabetes clinics. Euglycemic (5.3 mmol/liter) hyperinsulinemic (insulin infusion rate 9 micromoles x kg[-1] x min[-1]) clamp studies were performed before and after oral administration of pioglitazone (30 mg/day) for 87+/-10 days. The Rd significantly improved from 5.5+/-2.5 to 8.3+/-3.1 mg x kg(-1) x min(-1). Fasting plasma glucose (FPG) level significantly decreased from 11.0+/-2.0 mmol/liter to 8.9+/-1.1 mmol/liter with a significant improvement in the hemoglobin A1c level from 9.2+/-1.8% to 8.3+/-1.5%. Fasting serum insulin and C peptide levels decreased from 83+/-36 pmol/liter and 0.62+/-0.21 nmol/liter to 66+/-29 pmol/liter and 0.58+/-0.25 nmol/liter, respectively. Fasting serum triglyceride and free fatty acids levels significantly decreased with concomitant increase of fasting serum HDL-cholesterol levels from 1.2+/-0.2 to 1.5+/-0.3 mmol/liter. The change in Rd between before and after pioglitazone administration correlated with baseline values of FPG (rho=0.633), serum insulin (rho=0.653), BMI (rho=0.456), Rd (rho 0.558) and 1,5-AG (rho=-0.522). These data indicate that pioglitazone enhances the insulin action in NIDDM patients on diet alone or SU, and thereby improves both plasma glucose level and lipid profiles.
A study was conducted to examine the relationship of testicular atrophy to bone metabolism in male leprosy patients. The study consisted of 31 leprosy patients (mean age: 62.0 years) and 31 healthy control men (mean age: 60.0 years). Measurements were made of their serum levels of free testosterone (FT), estradiol (E2), luteinizing hormone (LH) and 25-hydroxyvitamin D (25 OHD). Bone mineral density (BMD) was measured at radial sites and the lumbar vertebral bodies (L2-L4) by dual-energy X-ray absorptiometry using a Hologic QDR-2000 densitometer. FT and E2 levels were significantly lower and LH levels higher in leprosy patients than in controls. This represents a primary hypogonadal pattern. A value of 7.20 pg/ml of FT ( = Mean - 1 SD of control) was used as a cut off value, and the subjects were subdivided into a hypogonadal group (HG) and a non hypogonadal group (non-HG). When the subjects were compared for differences in age, age at onset of disease, duration of disease, body mass index and BMD, only the duration of disease and BMD were significantly different between the two groups. Furthermore, BMD of the forearm significantly correlated with FT levels (r = 0.689, P < 0.0001). Low BMD may be due to orchitis and testicular atrophy.
A neonate male who developed cavernous angioma was born with a severe intraventricular hemorrhage and intraparenchymal hemorrhage in the basal ganglia. magnetic resonance imaging revealed a large, non-enhanced hematoma that packed the lateral ventricle. Surgery on the 2nd day of life verified a cavernous angioma associated with minimal hemosiderin and gliosis. Fetal cavernous angiomas, unlike such malformations in other age groups, can present with a devastating hemorrhage because of the lack of gliosis in the surrounding brain.
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Geriatric diseases have become significant problems in Japanese leprosariums. In particular, male osteoporosis seems to be more frequent in elderly leprosy patients than in non-leprosy elders. In 1987 we measured the cortical thickness of the 2nd metacarpal bone (MCI: metacarpal index) in 499 leprosy patients who were under medical treatment for osteoporosis. Of these patients, 139 were female patients with lepromatous leprosy (FL), 58 were female patients with tuberculoid leprosy (FT), 238 were male patients with lepromatous leprosy (ML) and the remaining 64 were male patients with tuberculoid leprosy (MT). The results were that the MCI of 238 ML was lower than 139 FL in the 4th, 5th 6th, and 7th decade of life. Furthermore the decreasing ratio of MCI peaked in the 4th decade was 70.6% between the ages of the 8th decade in ML. We conclude that this is a manifestation of leprosy-specific osteoporosis, which is associated with testicular dysfunction in elderly male patients with lepromatous leprosy.
We report a case of 53-year-old man with acute myelogenous leukemia (M2) showing a karyotype of t(7;11) (p15;p15), del(10) (q11;q12), who was complicated with perforation of a duodenal ulcer during the antileukemic chemotherapy using behenoyl ara-C, daunorubicin, 6-mercaptopurine and prednisolone. As his bone marrow still showed high cell density and leukemic proliferation at the time of intestinal perforation, the therapeutic regimen was changed to a combination of behenoyl are-C and mitoxantrone, and daily rhG-CSF was concurrently administered for the purpose of early establishment of bone marrow hypoplasia. On the 8th day after the therapeutic regimen had been changed, his bone marrow became nearly aplastic, and complete remission was obtained on the 24th day. This case may indicate that the concurrent administration of cell-cycle specific antileukemic drugs and rhG-CSF is available for AML patients with emergent need of leukemic cell reduction.
OBJECTIVES: Although percutaneous drainage has emerged as one of the first line of therapies for pyogenic liver abscesses, the presence of multiple abscesses may warrant surgical drainage, which remains controversial in the literature. We studied whether the multiplicity of the lesions influences the outcome of the treatment. METHODS: Ultrasonography-guided percutaneous drainage was carried out in 48 patients with pyogenic liver abscesses. The abscesses were solitary in 38 patients and multiple (two to seven lesions) in 10 patients. Clinical characteristics and the efficacy of the treatment were compared between these two groups. RESULTS: Biliary diseases and malignancies were more frequently observed in the solitary cases than multiple cases. A past history of surgery for cholelithiasis was seen exclusively in the multiple cases. E. coli was more frequently cultured from the abscesses in the multiple cases. Three of the multiple cases required more than a single catheter. All of the multiple cases and 36 of the 38 solitary cases were successfully treated. Two patients died of biliary peritonitis as a complication of the procedure, and three died of other underlining diseases. CONCLUSION: Ultrasonography-guided percutaneous drainage is effective even in patients with multiple pyogenic liver abscesses by adding catheters to obtain sufficient drainage.
Treatment results were evaluated in 45 children with acute myeloblastic leukemia (AML) treated on the ANLL-9205 protocol of the Children's Cancer Leukemia Study Group (CCLSG, Japan). In this protocol, terarubicin (THP-ADR), vincristine and continuous infusion of cytosine arabinoside (Ara C) were applied for remission induction therapy (AVC), and VP16+ high dose Ara C were used sequentially for 32 or 48 weeks. Eleven patients received stem cell transplantation. Thirty-eight out of the 43 eligible patients (88.4%) achieved complete remission, and the overall 3-year event-free survival (EFS) was 55.6% (S.E.,10%). This favorable response was attributed mainly to the high induction rate of patients with the M5, M7 FAB subtypes and higher WBC counts (> or = 10 x 10(9)/L). There was no difference in the 3-year EFS of these patients who discontinued treatment between 32 weeks and 48 weeks. Serious toxicities were not observed in this study. These findings suggest that the ANLL-9205 protocol is an effective and safe treatment regimen for childhood AML. When comparing the treatment period of 32 or 48 weeks, the difference was not statistically significant.
CBP, which is located on 16p13 and encodes a transcriptional adaptor/coactivator protein, has been shown to fuse by the t(8;16)(p11;p13) translocation to MOZ on 8p11 in acute myeloid leukemia. We found a t(11;16)(q23;p13) in a child with therapy-related chronic myelomonocytic leukemia. Subsequent reverse transcriptase-polymerase chain reaction and direct sequencing analyses revealed the MLL-CBP fusion transcript in CMML cells. Because 11q23 translocations involving MLL and t(8;16) involving MOZ and CBP have been reported in therapy-related leukemias, both the MLL and CBP genes may be targets for topoisomerase II inhibitors. Accordingly, we believe that most t(11;16)-associated leukemias may develop in patients who have been treated with cytotoxic chemotherapy for primary malignant diseases.
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The purpose of the present investigation was to develop a mattress which was made of the new synthetic fibers called 'Shin-Gosen', and to determine its physical characteristics associated with pressure sores such as pressure distribution, temperature and humidity. The Shin-Gosen mattress consisted of three layers of elastic fibers made of polyester multifilaments, which were mediated by four layers of wave-like fabrics made of nylon monofilaments. The physical characteristics of the mattress were compared with (a) the conventional cotton hospital mattress and (b) the SORELESS MAT made of vacuole gel which effectively eliminated compression forces. The Shin-Gosen mattress was found to provide pressure relief effects similar to that of the SORELESS MAT the desired thermal insulation as well as that of the cotton mattress and a higher level of moisture vapor permeability. These excellent features will not only contribute to preventing pressure sores, but will also enable comfortable resting and sleeping.
We studied the accuracy of left ventricular (LV) volumes and ejection fraction (EF) derived from ECG gated 99mTc-sestamibi myocardial perfusion SPECT (G-SPECT) and the software for automatic data analysis (QGS program described by Germano G et al.). G-SPECT was performed in 29 patients with various cardiac diseases. LV end-diastolic and end-systolic volumes (LVEDV and LVESV), and LVEF determined by QGS program were compared to those by Simpson method in biplane left ventriculography (LVG). Interobserver reproducibility in measuring the G-SPECT parameters was excellent (LVEDV: r = 0.99, LVESV: r = 0.99, LVEF: r = 0.97). There was a good correlation between the values obtained from G-SPECT and LVG (LVEDV: r = 0.92, LVESV: r = 0.94, LVEF: r = 0.85), but G-SPECT tended to underestimate LVEDV and LVEF. In 17 patients with moderate to severe myocardial perfusion defects selected from the subjects, the correlation was maintained fairly high (LVEDV: r = 0.90, LVESV: r = 0.92, LVEF: r = 0.77). In conclusion, QGS program provides high accuracy and reproducibility in determining LV volumes and LVEF from G-SPECT.
We report here two new cases of glucose phosphate isomerase (GPI) deficiency associated with hemolytic anemia and present the results of molecular analysis of the five Japanese GPI variants. A Japanese girl (GPI Fukuoka) had an episode of prolonged neonatal jaundice and at 3 years of age was admitted due to acute hemolytic crisis occurring with upper respiratory tract infection. Red blood cell (RBC) GPI activity was decreased to 11.8% of normal and the reduced glutathione (GSH) level of RBCs was slightly decreased. A 54-year-old Japanese man (GPI Iwate) was hospitalized due to chronic active hepatitis, and compensated hemolysis was noted. RBC GPI activity of the proband was decreased to 18.8%, and the GSH content was about half of the normal mean value. Sequencing of the reticulocyte GPIcDNA showed homozygous missense mutations 1028CAG-->CGG (343Gln-->Arg), 14ACC-->A7C (5Thr-->lle), 671ACG-->A7G (224Thr-->Met), and 1615GAC-->AAC (539Asp-->Asn) in GPI Narita, GPI Matsumoto, GPI Iwate, and GPI Fukuoka, respectively. We also identified GPI Kinki as a compound heterozygote of 1124ACA-->AGA(375Thr-->Arg)/ 1615GAC-->AAC(539Asp-->Asn). Our findings, together with the previous results of other investigators, showed that the GPI gene mutations so far identified were heterogeneous, although most GPI variants had common biochemical characteristics such as heat instability and normal kinetics. Several amino acid substitutions were identified in the proximity of the catalytically important amino acid residues such as Ser/Asp 159/160, Asp341, and Lys518, which have been identified in the structural analysis of the pig GPI. The molecular characterization of human GPI variants, therefore, may provide new insights into the genotype-phenotype correlation of GPI deficiency as well as the structure-function relationship of this enzyme.
Six hundred and twenty-seven cDNA clones from human brain cDNA libraries were characterized and integrated into a transcript map of the 1-Mb region on human chromosome 4p16.3 containing the Huntington's disease (HD) gene. Six hundred and seventy-two cDNA clones were obtained by a direct screening of the cDNA libraries, probing with pools of single copy microclones generated from the HD region specific yeast artificial chromosome (YAC)-DNA. So far, 93% of the obtained clones (627 cDNA clones) have been mapped onto the 1-Mb HD gene region by hybridization with HD region-specific cosmid, P1 and YAC clones. DNA sequence and expression analyses revealed that several cDNA clones might encode novel genes, some of which are situated within or close to the IT15, IT11, and alpha-adducin (ADD1) gene region, suggesting the presence of the overlapping genes in this region. This collection of cDNA clones will greatly facilitate the construction of the complete map of the transcripts in the HD region.
Phosphoenolpyruvate carboxylase (PEPC) was purified for the first time from hyperthermophilic archaeon Methanothermus sociabilis, growing autotrophically with an optimum at 88 degrees C. The optimum temperature for enzyme activity was similar to that for growth and was 85 degrees C. The native enzyme was a homotetramer of 240 kDa molecular mass and the subunit displayed an apparent molecular mass of 60 kDa. The archaeal PEPC was insensitive to various metabolites which are known as allosteric effectors for most bacterial and eucaryal counterparts. The enzyme showed extreme thermostability such that there remained 80% of the enzyme activity after incubation for 2 h at 80 degrees C. These results implied that archaeal PEPC was significantly different from bacterial and eucaryal entities.