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Biomedical subjects

K Nonaka

Publications and source records attributed to K Nonaka.

At least 91 records · Page 5Linked to original sources

Clinical characterization of polymorphisms in the sulphonylurea receptor 1 gene in Japanese subjects with Type 2 diabetes mellitus.

To assess the association of polymorphisms at the sulphonylurea receptor (SUR1) gene with the development of Type 2 diabetes mellitus, 456 subjects, 236 with Type 2 diabetes and 220 non-diabetic controls, were analysed for variants at exon 7, exon 22 and intron 24 of the SUR1 gene by the polymerase chain reaction and restriction fragment length polymorphism. The T761T substitution in exon 22 of the SUR1 gene was not found in either diabetic patients or non-diabetic controls. Both the exon 7 variant and the intron 24 variant were present in both groups at similar frequencies. No significant association was seen between either variant and obesity. Diabetic patients homozygous for the -3C allele of intron 24 had a higher ratio of positive family history than patients homozygous for the -3T allele (p = 0.03). We conclude that these polymorphisms are not major determinants of diabetes and obesity in the Japanese population.

ATP-Binding Cassette Transporters↗

[Pseudo-aneurysm of aortic arch and rupture into pericardium, a case report of successful surgical management].

This is a case report of 50 years old male suffering from pyrexia and epigastralgia 2 weeks prior to admission. On the 15th hospital day, he complained chest pain. Chest roentgenography revealed marked expansion of the mediastinum which was not existed upon admission. CT and MRI of the chest demonstrated a pseudoaneurysm of aortic arch at lesser curvature with extension into the pericardium. Exploration of the pericardium through median sternotomy disclosed fully filling with purulent effusion and blood clots. Following irrigation of the pericardial space and tube drainage, chest was closed. Repair of the aneurysm was postponded. Following continues irrigation of the pericardial space for 19 days, tube graft replacement of the aneurysm was performed under femorofemoral bypass and circuratory arrest through left thoracotomy. The aneurysmal space was filled with the omental pedicle to control infection. However, repeated bacteriological examination of the pericardium and aneurysm revealed no growth. Behçet disease was most suspected in report of the pathology.

Aneurysm, False↗

[Surgical treatment for chronic dissecting aneurysm (DeBakey type I)--a case using "elephant trunk" and "aortic tailoring"].

We present a surgical case of a 54-year-old man with chronic dissecting aortic aneurysm (Type I). At the first operation, ascending aorta and aortic arch were replaced with a tube graft under cardiopulmonary bypass and selective cerebral perfusion. Elephant trunk method was employed for the second operation. At the second operation, graft replacement of the proximal two-thirds of the descending aorta was performed, and the lower third of the descending aorta was tailored. Aortic tailoring consisted of the longitudinal aortomy and the removal of the initimal flap from the distal part of the descending aorta from the level of the 9th intercostal artery down to the diaphragm. The aorta was closed creating single channel 21 mm in diameter and containing the origins of the important intercostal arteries. He discharged the hospital without any complication including paraplegia or visceral ischemia, and his follow-up CT scan (1 year-later) did not show any dilatation of the tailored segment of the descending aorta and abdominal aorta.

Aortic Dissection↗

[Postoperative compartment syndrome in a patient with acute aortic dissection (DeBakey type I)].

We report a case of compartment syndrome caused by femoral arterial cannulation during cardiopulmonary bypass. A 62-year-old man who had been diagnosed as acute aortic dissection (type I) received a operation of partial arch replacement with reconstruction of brachiocephalic and left carotid arteries. Compartment syndrome was noticed just after the operation, which was caused by long-term ischemia during femoral arterial cannulation combined with poor collateral circulation by the dissection of iliac arteries. The emergency fascitomy was performed, therefore, he could be discharged without any complications. It is concluded that in case of acute aorte aortic dissection, the back-flow of blood should be checked at the time of femoral arterial cannulation, and whenever the back-flow is poor, some procedures should be added to increase distal blood flow.

Acute Disease↗

[Aortic root replacement by cryopreserved homograft for prosthetic valve detachment case due to aortitis].

We present a surgical case of a 35-year-old man with aortitis. He had been performed the reconstruction of the right common carotid artery with a saphenous vein graft at 23 years old for his ruptured aneurysm by aortitis. The aortic valve replacement and CABG (LITA to LAD, SVG to D1 and SVG to RCA) were performed for aortic regurgitation and aneurysms of coronary arteries two years ago. The diastolic murmur was first heard at 18 months after the operation. The echocardiography on admission showed an abnormal movement of the prosthetic valve with perivalvular leakage. At the second operation, the valve dehiscence was observed. Although the tissues around the dehiscence was friable and edematous, there were no signs of vegetation nor abscess formation. His aortic root was replaced with a cryopreserved aortic allograft conduit. His postoperative course was uneventful and aortography revealed neither aortic regurgitation nor stenosis of the coronary artery or SVGs. We think the softness of the allograft valve ring is favorable in valve detachment cases due to not only infection but also aortitis, to prevent redetachment.

Adult↗

Identification of a single nucleotide insertion polymorphism in the upstream region of the insulin promoter factor-1 gene: an association study with diabetes mellitus.

Insulin promoter factor 1 (IPF1) is a key factor both for the regulation of insulin gene expression and for the development of the pancreas. In this study 88 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were diagnosed as diabetic at less than 40 years of age, 55 patients with insulin-dependent-diabetes (IDDM), and 67 normal control subjects were analysed for variants in the upstream region of the IPF1 gene by direct sequencing. A novel single nucleotide insertion polymorphism was found in a guanine triplet at 108 bp upstream of the translation start site. The G insertion allele (G4 allele) was found to be common in the Japanese population, at a frequency of 0.50. The prevalence of G3 homozygotes was higher in IDDM patients (35%) and lower in NIDDM patients (17%) than in normal control subjects (28%, p=0.049). In the NIDDM group, the ratio of insulin treatment tended to be higher in subjects homozygous for the G3 allele, although the genotype was not significantly associated with basal C-peptide levels. The polymorphism is unlikely to be a major contributor to the insulin deficiency of diabetes. However, the polymorphic locus, or an unknown mutation which is in linkage disequilibrium with the polymorphism, could be involved in the pathophysiology of diabetes. The high heterozygosity may be useful for genetic linkage studies of other mutations within and near the IPF1 gene.

Adolescent↗

Technetium-99m tetrofosmin imaging in patients with subacute thyroiditis.

We studied the significance of technetium-99m tetrofosmin scintigraphy in patients with subacute thyroiditis (SAT). Six patients with SAT, who had painful goitre with thyrotoxicosis, underwent 99mTc-pertechnetate scintigraphy and 99mTc-tetrofosmin imaging during the acute and recovery stages of SAT. The thyroid uptake ratio of tetrofosmin was compared with the clinical parameters associated with SAT. 99mTc-pertechnetate scintigraphy showed markedly reduced uptake in the thyroid during the acute stage of SAT, suggesting that the appropriate metabolic pathway is not functioning. Conversely, 99mTc-tetrofosmin images showed diffuse increased uptake in the thyroid region on early and delayed imaging. Tetrofosmin images in the acute stage and in the recovery stage of SAT showed different clearance curves for tetrofosmin uptake. The uptake ratio assessed as thyroid uptake/background (T/B) correlated with the serum C-reactive protein concentration. In conclusion, 99mTc-tetrofosmin uptake may reflect the inflammatory process associated with SAT, and thus this tracer may have potential as a marker of disease activity and severity.

Adult↗

Marriage season, promptness of successful pregnancy and first-born sex ratio in a historical natural fertility population--evidence for sex-dependent early pregnancy loss?

We investigated population-based vital records of the seventeenth and eighteenth century French Canadian population to assess the effects of marriage season on the outcome of the first births under natural fertility conditions (n = 21,698 marriages). Promptness of the first successful conception after marriage differed according to marriage season; the proportion of marriages with a marriage-first birth interval of 8.0-10.0 months was lowest (34%) for marriages in August-October (P = 0.001). Although the male/female sex ratio of the babies born with an interval of 8.0-10.0 months was generally higher (1.10) than those with an interval of 10.0-24.0 months (1.05), the marriages in August-October resulted in a significantly reduced sex ratio (0.96) among only the prompt conceptions (P = 0.026). We discuss whether this seasonal reduction of the sex ratio could be partly explained by a clustered pregnancy loss of male zygotes in early pregnancy.

Adult↗

Cerebral revascularization using omentum and muscle free flap for ischemic cerebrovascular disease.

BACKGROUND: Indirect cerebral revascularization has been generally accepted in the management of brain ischemia in moyamoya disease. We performed indirect cerebral revascularization by using omental flap and muscle flap techniques for the treatment of ischemic cerebrovascular disease. METHODS: Ten patients with ischemic cerebrovascular disease including three with adult moyamoya disease underwent this procedure (omental flap on eight sides and muscle flap on five sides). The muscle used for the flap was the serratus anterior muscle on two sides and shaved latissimus dorsi muscle on three sides. Angiography and cerebral blood flow studies were performed in all patients preoperatively and postoperatively. All patients demonstrated severely impaired cerebrovascular reserve capacity due to occlusive disease. RESULTS: There was one patient each with perioperative death and intracranial infection following omental flap loss, and two patients had perioperative strokes. The average follow-up period was 23.2 months. Of the nine surviving patients, all eight except for the one with flap loss had good outcome with complete resolution of neurologic episodes. CONCLUSIONS: It is concluded that this method seems to be effective in selected patients with ischemic cerebrovascular disease.

Adult↗

Yearly changes in stillbirth rates of zygotic twins in Japan, 1975-1994.

The stillbirth rates decreased to 2/3 for MZ male twins, 1/2 for MZ female twins, and under 1/2 for DZ twins for both sexes during the 19-year period from 1975 in Japan. The stillbirth rate was significantly higher in MZ males than MZ females in each year, whereas stillbirth rates of DZ twins for both sexes indicated similar values during that period. After 1986, stillbirth rates were more than 2 times higher in MZ twins than in singletons and in DZ twins. The higher stillbirth rate of MZ twins as opposed to DZ twins could be related to monochorionic twin pairs in MZ twins. The stillbirth rate decreased more drastically in twins for both zygosities than in singleton births during the 34-year period from 1960. However, declining rates of stillbirths may be attributed to medical care during twin pregnancies. Recommendation of an optimum day to give birth for twin pregnancy is 37-38 weeks for Japanese women.

Birth Weight↗

Possible involvement of Fas-mediated apoptosis in eye muscle tissue from patients with thyroid-associated ophthalmopathy.

In order to investigate the possible involvement of apoptosis in the pathogenesis of thyroid-associated ophthalmopathy (TAO), we studied the expression of Fas, Fas ligand (FasL), and Bcl-2 in extraocular muscle tissues from patients with TAO by immunohistochemistry using monoclonal antibodies against Fas, FasL, and Bcl-2. Apoptosis was detected by in situ end-labeling of fragmented DNA. Apoptosis was detected in extraocular muscle tissues from 17 of 19 patients with TAO and, to a smaller degree in 4 of 7 normal control subjects. The mean percentages of apoptotic nuclei were 12.1% in TAO eye muscle fibers and 16.4% in TAO interstitial cells, compared with 2.2% and 0.4% in normal eye muscle fibers and interstitial cells, respectively. The percentage of apoptotic nuclei in eye muscle fibers correlated with the enlargement of eye muscle tissue (r = 0.47, p < 0.05). Fas was demonstrated on the surfaces of extraocular muscle fibers in 11 of 18 patients with TAO, but not in normal extraocular muscle tissues. Neither TAO nor normal extraocular muscle tissues expressed Bcl-2. FasL was detected in infiltrating mononuclear cells in extraocular muscle tissue from a patient with TAO. These data suggest that Fas-mediated apoptosis may occur in extraocular muscle tissue from patients with TAO and may be involved in the late stage of TAO.

Adult↗

Nicotinamide decreases cytokine-induced activation of orbital fibroblasts from patients with thyroid-associated ophthalmopathy.

We used flow cytometry to investigate the effects of nicotinamide, an inhibitor of poly (ADP ribose) synthetase, on the cell-surface expression of cytokine-induced human leukocyte antigen (HLA)-A,B,C antigen, HLA-DR antigen, intercellular adhesion molecule 1, CD44, and Fas expression in cultured orbital fibroblasts from patients with thyroid-associated ophthalmopathy. After two to seven passages, cultured orbital fibroblasts were incubated for 3 days with interferon gamma or tumor necrosis factor alpha in the presence of nicotinamide. Nicotinamide inhibited the induction of both HLA-DR and intercellular adhesion molecule 1 expression by cytokines on fibroblasts but did not interfere with induction of HLA-A,B,C, or CD44 expression. Nicotinamide also inhibited the proliferation of orbital fibroblasts, as assessed by a [3H]-thymidine incorporation assay and cell counts. Nicotinamide also enhanced the expression of the apoptosis-mediating protein Fas on fibroblasts. Our data suggest that nicotinamide inhibits cytokine-induced activation of fibroblasts and thus may decrease the autoimmune injury to the orbit in thyroid-associated ophthalmopathy.

Adipose Tissue↗

Codon 972 polymorphism of the insulin receptor substrate-1 gene in impaired glucose tolerance and late-onset NIDDM.

OBJECTIVE: To assess the relevance of a Gly-->Arg substitution in codon 972 of the insulin receptor substrate-1 gene in impaired glucose tolerance (IGT) and NIDDM. RESEARCH DESIGN AND METHODS: The genotype of 1,106 Japanese subjects consisting of 310 subjects with NIDDM, 305 subjects with IGT, and 491 normal control subjects was analyzed by an allele-specific assay using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The frequency of the variant allele was not different between subjects with NIDDM (0.021) and normal control subjects (0.020). However, subjects with IGT showed a significantly higher prevalence of the variant allele (0.041, P = 0.027). We found two homozygous individuals for the variant; both had IGT with mild insulin resistance. The allelic frequency tended to be lower in normal control subjects aged > 50 years than in younger control subjects. Conversely, in the subjects with IGT or NIDDM, the Gly972Arg substitution was more frequently found in subjects aged > 50 years. Furthermore, NIDDM patients with the variant allele had older ages of diagnosis than patients without the variant. CONCLUSIONS: The codon 972 variant may be associated with IGT and a subset of late-onset NIDDM in the elderly Japanese population.

Adult↗

A patient with Paget's disease of bone treated with etidronate disodium.

A 69-year-old Japanese woman was referred to our hospital because of abnormal skull X-ray findings. Serum total alkaline phosphatase, bone-specific alkaline phosphatase 3, osteocalcin and propeptide carboxyterminal of type I procollagen (PICP) levels were markedly elevated. Urinary excretion of hydroxyproline was also increased, suggesting that both bone formation and resorption were accelerated. Radiography of the skull showed "cotton wool" appearance. T1-enhanced MRI revealed that the skull-cap and diploe were swelled up. In 99mTc-MDP bone scintigraphy, all areas of the skull and a part of the right hemipelvis showed high uptake of the radioisotope. Based on the findings we made diagnosis of Paget's disease of bone which is a rare bone disorder in Japanese. Three-month oral administration of etidronate disodium resulted in normalization of serum PICP levels and urinary hydroxyproline excretion, whereas alkaline phosphatase levels were only partially lowered. Levels of the markers of bone turnover remained normal during a follow-up period of 3 months after the discontinuation of the treatment.

Aged↗

High density culture of immortalized liver endothelial cells in the radial-flow bioreactor in the development of an artificial liver.

Liver endothelial cells are important components of the tissue along the hepatic sinusoid. They are responsible for microcirculation in the liver and scavenger functions. It would therefore be important to include these cells in any hybrid type of artificial liver in addition to hepatocytes. However, it is difficult to culture these cells in vitro. The development of a liver endothelial cell line, which maintains the characteristics of the primary culture, would thus be of great benefit in the development of an artificial liver. In the present study we established immortalized liver endothelial cells from the liver of an H-2Kb-tsA58 transgenic mouse, which harbors the SV40 TAg gene. Hepatic sinusoidal cells isolated from H-2Kb-tsA58 mouse proliferated in the presence of gamma-interferon at 33 degrees C. Four clones were established, out of which clone M1 had the highest amounts of PGI2 production, as well as plasminogen activator activity and internalized acetylated low density lipoprotein. On culture dishes the M1 cells grew individually and spread. Sieve plates on the cell surface were not readily visible, but small pores were detected under electron microscopic observation. These results suggest that M1 clone cells originated from liver endothelial cells. Moreover it was possible to culture the immortalized liver endothelial cells in a radial-flow bioreactor for 5 days, with a maximum 6-keto prostaglandin F1alpha production of 25 microg per day. This suggests that immortalized liver endothelial cells and a radial-flow bioreactor can prove useful tools in the development an artificial liver.

Animals↗

Respiratory impairments due to dust exposure: a comparative study among workers exposed to silica, asbestos, and coalmine dust.

We conducted a comparative study of pulmonary dysfunction among workers who were exposed to silica, asbestos, or coalmine dust. The results showed that all three groups of dust-exposed workers, even those without radiographic signs of pneumoconiosis, had decreased spirometric parameters and diffusing capacity (DLco) in both nonsmokers and smokers. Pulmonary function was further decreased when pneumoconioses were present in the three groups. In accord with increasing radiographic categories, pulmonary function in the workers with either silicosis or asbestosis was even lower, whereas in those with coal workers' pneumoconiosis (CWP), it changed relatively little. Workers with mild to moderate (radiographic category I-II) silicosis or asbestosis showed similarly decreased DLco, but those with silicosis showed lower FEV1/FVC than those with abestosis. The workers with CWP also showed a lower FEV1/FVC than those with asbestosis. The major impairment patterns for silica workers, asbestos workers, and coal miners were mixed, restrictive and mixed, and obstructive, respectively. Smoking obviously increased the prevalence of obstruction for all the groups. We conclude from the present study that all the three dusts cause functional abnormalities that precede radiographic changes of pneumoconiosis. We should pay more attention to respiratory impairment in the initial stage of silicosis and CWP.

Adult↗

Neurotoxicity of serum components, comparison between CA1 and striatum.

In vasogenic brain edema, the neurotoxicity of extravasated serum components may contribute to neuronal damage. In the hippocampal CA1 sector and striatum, the neurotoxicity of serum was investigated. Rat serum was prepared as follows: Serum-1: whole serum, Serum-2: ultrafiltrated through a membrane with cut-off at molecular weight (MW) 100,000. Serum-3: through a membrane with cut-off at MW 20,000, and Serum-4: through a membrane with cut-off at MW 5,000. The infusion edema model was utilized for infusion of autologous serum into the brain. The brain tissue was histologically evaluated. The level of glutamate, total protein, and albumin was also measured in the sera used for infusion. The following results were obtained: 1) CA1 neurons were more vulnerable to all infused sera than striatal neurons, 2) there was a strong cellular response in the striatal site of infusion, but only a minimal in the CA1-sector, 3) the severity of damage of CA1 correlated with the glutamate concentrations of the infused sera, 4) further, there was a relationship between the degree of striatal neuronal loss and the amount of protein and albumin present in the infusate. It is, therefore, concluded that the neurotoxic properties of vasogenic edema fluid are also affected by specific features of the brain region of its extravasation. In addition, the pathological mechanisms associated with irreversible damage of neurons might be different in the CA1-sector and the striatum.

Animals↗