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Biomedical subjects

M Sakuma

Publications and source records attributed to M Sakuma.

At least 19 recordsLinked to original sources
PubMed2006

Vitamin D and intact PTH status in patients with hip fracture.

INTRODUCTION: The prevalence of hypovitaminosis D in patients with acute hip fracture was examined in a population on Sado Island in Japan. There were 85 cases of hip fracture among this population in 2004, giving an overall incidence of hip fracture of 121.4 per 100,000 population per year. This study included 50 of the 85 cases, and these cases were defined as the hip fracture group. Patients older than 70 years without established osteoporosis who were admitted to the hospital on the island during almost the same period for treatment of an orthopedic condition other than a hip fracture were defined as the control group. MATERIALS AND METHODS: The levels of serum 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (intact PTH), alkaline phosphatase (ALP), albumin, and the number of remaining teeth were examined in each group. In the hip fracture group, serum calcium, serum phosphorus, urine N-terminal cross-linking telopeptide of type I collagen (NTx), bone mineral density (BMD) of the nonfractured hip, the presence of a vertebral fracture on X-ray, severity of dementia, and physical activity level were also examined. RESULTS: Both the serum 25-OHD and serum albumin levels were significantly lower in patients with hip fracture than in controls, and the intact PTH level was significantly higher in patients with hip fracture. The number of remaining teeth was correlated with age, and was also significantly correlated with 25-OHD. In the hip fracture group, 62% of the subjects had hypovitaminosis D (25-OHD <20 ng/ml) and one-fifth of cases with hypovitaminosis D showed elevated PTH levels (>65 pg/ml). On the other hand, in the control group, hypovitaminosis D occurred in 18.9% of the subjects, and only one case showed elevated PTH. The serum 25-OHD level showed a decrease as the severity of dementia progressed and the activity level decreased. CONCLUSION: Our results indicate that about two-thirds (62%) of hip fracture patients had vitamin D insufficiency, suggesting that this condition may be closely associated with hip fracture in elderly people. Therefore, the serum 25-OHD level may be a useful index for the risk of hip fracture in elderly people.

Aged↗
PubMed2002

Acute myocardial infarction associated with myocardial bridge and coronary artery vasospasm.

A 65-year-old man was admitted to our hospital with acute myocardial infarction (MI). Emergency coronary angiography showed no significant organic lesions, but a myocardial bridge was found at the mid-left anterior descending artery An acetylcholine provocation test revealed 90% spastic stenosis just proximal to the myocardial bridge. His acute MI could have been caused by both a coronary spasm and the myocardial bridge.

Acetylcholine↗
PubMed2001

Docking protein Gab2 is phosphorylated by ZAP-70 and negatively regulates T cell receptor signaling by recruitment of inhibitory molecules.

To maintain various T cell responses and immune equilibrium, activation signals triggered by T cell antigen receptor (TCR) must be regulated by inhibitory signals. Gab2, an adaptor protein of the insulin receptor substrate-1 family, has been shown to be involved in the downstream signaling from cytokine receptors. We investigated the functional role of Gab2 in TCR-mediated signal transduction. Gab2 was phosphorylated by ZAP-70 and co-precipitated with phosphoproteins, such as ZAP-70, LAT, and CD3zeta, upon TCR stimulation. Overexpression of Gab2 in Jurkat cells or antigen-specific T cell hybridomas resulted in the inhibition of NF-AT activation, interleukin-2 production, and tyrosine phosphorylation. The structure-function relationship of Gab2 was analyzed by mutants of Gab2. The Gab2 mutants lacking SHP-2-binding sites mostly abrogated the inhibitory activity of Gab2, but its inhibitory function was restored by fusing to active SHP-2 as a chimeric protein. A mutant with defective phosphatidylinositol 3-kinase binding capacity also impaired the inhibitory activity, and the pleckstrin homology domain-deletion mutant revealed a crucial function of the pleckstrin homology domain for localization to the plasma membrane. These results suggest that Gab2 is a substrate of ZAP-70 and functions as a switch molecule toward inhibition of TCR signal transduction by mediating the recruitment of inhibitory molecules to the TCR signaling complex.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Questionnaire-based assessment of pelvic organ dysfunction in Parkinson's disease.

Although patients with Parkinson's disease (PD) experience pelvic organ dysfunction of the urinary bladder, bowel and genital organs, an accurate incidence of the dysfunction and its characteristics have yet to be ascertained. We devised a detailed questionnaire on these three pelvic organ functions in PD patients and control subjects, in our search for a hallmark that would distinguish between the two groups. The PD group comprised 115 patients; 52 men and 63 women, age range 35-69 (average 59) years old, average duration of illness 6 years, median Hoehn and Yahr stage 3. All were taking levodopa with/without dopamine agonists. The control group comprised 391 local individuals who were undergoing an annual health survey; 271 men and 120 women, age range 30-69 (average 48) years old. The questionnaire had three parts: bladder (nine questions), bowel (four questions), and sexual (three questions for women, five for men) function. Each question was scored from 0 (none) to 3 (severe) with an additional quality of life (QOL) index scored from 0 (satisfied) to 3 (extremely dissatisfied). The completion rate was 100% for bladder and bowel functions, whereas for sexual function, it was 95% (control) and 88% (PD) for men and 82% (control) and 60% (PD) for women. As compared with the control group, the frequency of dysfunction in the PD group was significantly higher for urinary urgency (women 42%, men 54%), daytime frequency (28%, 16%), nighttime frequency (53%, 63%), urgency incontinence (25%, 28%), retardation (44% of men), prolongation/poor stream (men 70%), straining (women 28%); constipation (63%, 69%), difficulty in expulsion (men 57%), diarrhea (men 21%); decrease in libido (84%, 83%), decrease in sexual intercourse (55%, 88%), decrease in orgasm (men 87%), and in men, decreases in erection (79%) and ejaculation (79%). The QOL index for the PD patients was significantly higher for bladder (27%, 28%) and bowel (46%, 59%) but not for sexual dysfunction, despite the group's high prevalence of sexual dysfunction. In the PD patients, fecal incontinence was associated with urinary incontinence. Stress urinary incontinence and a decrease in libido were more common in women than in men. Bladder and bowel dysfunction, but not sexual dysfunction increased with the Hoehn and Yahr stage. Sexual dysfunction, but neither bladder nor bowel dysfunction, increased with age. Patients taking levodopa and bromocriptine more frequently had bladder (voiding phase) dysfunction than those taking levodopa only. The findings show that bladder, bowel and sexual dysfunction are all prominent in patients with PD. Amelioration of pelvic organ dysfunction, particularly bowel dysfunction which most affects the quality of life, therefore should be a primary target in the treatment of patients with PD.

Adult↗
PubMed2001

Uncoupling protein 3 and peroxisome proliferator-activated receptor gamma2 contribute to obesity and diabetes in palauans.

We examined the genetic contribution of single nucleotide polymorphisms (SNPs) of the energy metabolism-related genes, including beta 3 adrenergic receptor (beta3AR), apolipoprotein E (apo-E), promoter of uncoupling protein 3 (UCP3-p), peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) and leptin receptor (LEPR) to metabolic disorders, in 118 inhabitants of Palau. The data were statistically analyzed and ethnically compared to correlate SNPs and their metabolic parameters. UCP3-p (P < 0.01) and PPARgamma2 (p = 0.05) correlated with plasma HbA1c, and UCP3-p correlated with fasting blood glucose (P < 0.01) in males, but not in females. UCP3-p correlated with body fat (%) (P < 0.01) in females, but not in males. Plasma leptin levels and apo-E were correlated in both groups. The frequency of SNPs for PPARgamma2, LEPR, and UCP3-p are significantly different between Palauans and Caucasians.

Adipose Tissue↗
PubMed2001

Clinical characteristics of acute pulmonary thromboembolism in Japan: results of a multicenter registry in the Japanese Society of Pulmonary Embolism Research.

BACKGROUND: Although the incidence of acute pulmonary thromboembolism (APTE) has been increasing in Japan, patient characteristics, management strategies, and outcome have not yet been assessed in large series. HYPOTHESIS: The present study was designed to investigate the current status of APTE in Japan. METHODS: Of a total of 533 registry patients with pulmonary thromboembolism, 309 with APTE were analyzed with respect to clinical symptoms and signs, predisposing factors, diagnostic procedures, estimation of deep venous thrombosis, treatment, and clinical course. RESULTS: Main risk factors were recent major surgery, cancer, prolonged immobilization, and obesity; only a few patients had coagulopathy and 36% were in cardiogenic shock at presentation. The majority of registry patients underwent lung scans or pulmonary angiography; 30% were diagnosed only by lung scanning. Venous ultrasonography was used in only 34 patients, while 188 patients underwent at least one diagnostic procedure for deep venous thrombosis. Thrombolysis was more frequently performed in patients with cardiogenic shock, and only a few patients received thromboembolectomy. In-hospital mortality rate was 14%. In patients with cardiogenic shock, the mortality rate was reduced by thrombolysis. The predictors of in-hospital mortality were male gender, cardiogenic shock, cancer, and prolonged immobilization. CONCLUSIONS: The patients in this registry had almost the same findings as those in Western patients, except for some points that had the possibility of demonstrating a difference between Westerners and Japanese in the development of APTE. These results can prove especially helpful in planning prospective, randomized trials that will clarify the impact of widely used treatment modalities on the outcome of patients with APTE.

Age Distribution↗
PubMed2001

[Angiography of pulmonary hypertension].

In the present report, we reviewed articles on pulmonary angiography for patients with pulmonary hypertension. The use of a non-ionic, low-osmolarity agent and improvements in catheters reduced periprocedual complications, but attention should be paid to the pre-existing poorer physical state. Digital pulmonary angiography has similar diagnostic power to conventional angiography. Wedged pulmonary angiography could demonstrate distal lesions of the pulmonary artery which couldn't be detected by conventional pulmonary angiography. Typical pulmonary angiograms from pulmonary hypertension due to pulmonary embolism, primary pulmonary hypertension, collagen diseases, Takayasu's arteritis and porto-pulmonary hypertension were shown. Pulmonary angiography is relatively less valuable than before because of advances in other diagnostic imaging tools, but still remains the gold standard.

Angiography, Digital Subtraction↗
PubMed2000

Regulation of cell surface expression of CTLA-4 by secretion of CTLA-4-containing lysosomes upon activation of CD4+ T cells.

CTLA-4 is expressed on the surface of activated T cells and negatively regulates T cell activation. Because a low-level expression of CTLA-4 on the cell surface is sufficient to induce negative signals in T cells, the surface expression of CTLA-4 is strictly regulated. We previously demonstrated that the association of CTLA-4 with the clathrin-associated adaptor complex AP-2 induces internalization of CTLA-4 and keeps the surface expression low. However, the mechanism to induce high expression on the cell surface upon stimulation has not yet been clarified. To address this, we investigated the intracellular dynamics of CTLA-4 by analyzing its localization and trafficking in wild-type and mutant CTLA-4-transfected Th1 clones. CTLA-4 is accumulated in intracellular granules, which we identified as lysosomes. CTLA-4 is degraded in lysosomes in a short period, and the degradation process may serve as one of the mechanisms to regulate CTLA-4 expression. Upon TCR stimulation, CTLA-4-containing lysosomes are secreted as proven by the secretion of cathepsin D and beta-hexosaminidase in parallel with the increase of surface expression of CTLA-4 and lysosomal glycoprotein 85, a lysosomal marker. These results suggest that the cell surface expression of CTLA-4 is up-regulated upon stimulation by utilizing a mechanism of secretory lysosomes in CD4(+)T cells.

Abatacept↗
PubMed2000

Current status of thromboangiitis obliterans (Buerger's disease) in Japan.

We analysed clinical features and outcome in 850 patients with thromboangiitis obliterans (TAO), based on the 1993 Nationwide Survey of Vasculitis database collected from 3722 clinical sites in Japan. The survey was designed to assess clinical manifestation categorized by Fontaine's classification, distribution of lesions (arterial involvement and migratory superficial phlebitis), response to medical and surgical treatment, and outcome. There were 771 males (90.7%) and 79 females (9.3%), with a mean age of 50.8+/-0.4 (range: 17-81) years. Clinical manifestations at the first consultation were Fontaine I in 8.0%, Fontaine II in 29.6%, Fontaine III in 23.9%, and Fontaine IV in 38.1%. These symptoms had been significantly improved by the time of survey. Ulcer formation in the past history had occurred in 45.2%, which was the most common in toes (85.9%). Failure of smoking cessation significantly affected the risk of ulcer formation (odds ratio=1.71, 95% CI=1.19-2.47; P=0.004) and amputation (odds ratio=2.73, 95% CI=1.86-4.01; P<0.0001). Clinical features in female patients with TAO were equal to those in male patients, except for the fact that non-smokers were more common in female patients. Abstinence from tobacco significantly reduces the risk of ulcer formation and amputation, and thus improves the quality of life in patients with TAO.

Adult↗
PubMed2000

A Di-leucine signal in the ubiquitin moiety. Possible involvement in ubiquitination-mediated endocytosis.

Some plasma membrane receptors in yeast are known to be internalized and degraded in lysosomes upon ligand-dependent ubiquitination. However, the role of ubiquitination in endocytosis and lysosomal degradation in higher eukaryotes has been controversial. In order to directly assess this question, we investigated the fate of chimeric molecules in which ubiquitin moiety was fused in-frame to the cytoplasmic region of membrane proteins. The chimeric proteins with the wild-type ubiquitin were endocytosed and delivered to lysosomes efficiently. Mutant ubiquitin with lysine-to-arginine substitution could still mediate endocytosis, suggesting that polyubiquitination is not required for the endocytosis. We next searched for the existence of an endocytosis signal(s) in the ubiquitin moiety, and identified a di-leucine signal, Leu(43)-Ile(44). The Leu(43)-Ile(44) sequence mediated endocytosis and lysosomal sorting in a Leu(43)-dependent manner. These results suggest that the di-leucine signal in ubiquitin can be involved in ubiquitination-mediated endocytosis and lysosomal targeting of membrane proteins.

Amino Acid Sequence↗
PubMed2000

Distribution of arterial involvement in thromboangiitis obliterans (Buerger's disease): results of a study conducted by the Intractable Vasculitis Syndromes Research Group in Japan.

The clinical profile of thromboangiitis obliterans (TAO) has been changing. The purpose of this study was to clarify the distribution of arterial involvement in this disease, based on a nationwide survey carried out in 1993. A total of 825 TAO patients with complete records were analyzed. There were 749 men and 76 women, with a mean age of 50.8 +/- 0.4 years. The survey assessed clinical manifestations categorized by Fontaine's classification, distribution of the lesions, associated diseases, responses to treatment, and outcome. This study focused on the distribution of arterial involvement. There were 42 patients (5.1%) with upper-extremity arterial involvement only, 616 (74.7%) with lower-extremity involvement only, and 167 (20.2%) with both. The most frequently affected arteries were the anterior (41.4%) or posterior (40.4%) tibial arteries in the lower extremities, and the ulnar artery (11.5%) in the upper extremities. There were no significant differences in the distribution of arterial involvement between men and women or between the right and left sides. In conclusion, approximately 25% of the patients had upper-extremity involvement. The anterior or posterior tibial arteries were most commonly affected. There was no significant difference in the distribution of arterial involvement between male and female patients.

Adolescent↗
PubMed2000

Idiopathic adrenal hemorrhage.

A case of idiopathic adrenal hemorrhage is reported. A 76-year-old woman exhibited a left adrenal tumor, 3 cm in diameter, on abdominal computed tomography. The patient was receiving aspirin medication for atrial fibrillation. There was no evidence of increased adrenal hormones. The mass enlarged to 6 cm in diameter within 18 months, and malignancy was suspected. The mass was diagnosed as adrenal hematoma by operative findings.

Adrenal Gland Diseases↗
PubMed2000

Protective role of extracellular superoxide dismutase in hemodialysis patients.

BACKGROUND: The superoxide anion and other oxygen radicals have been implicated in the progression of chronic renal failure, and are removed by extracellular superoxide dismutase (EC-SOD) in the extracellular space on the surface of the endothelium. A single-base substitution of the EC-SOD gene which reduces the binding capability to endothelial cells resulting in an increased serum concentration, has been identified in healthy persons and hemodialysis patients. RESULTS: The proportion of patients with this mutation among hemodialysis patients in each 20 months' duration after the initiation of hemodialysis was retrospectively studied. The percentage of substitution-positive patients declined 80 months after the start of hemodialysis in non-DM patients. In contrast, in DM patients, the rapid decrease was obvious as early as 40 months after the initiation of hemodialysis. By prospective study for 5 years, there were significant differences in the survival rate between patients with and without R213G in DM, but not in non-DM patients. Among those who died, the incidence of ischemic heart disease and cerebrovascular disease in cases with R213G was significantly higher than in cases without R213G. CONCLUSION: These results suggest that the presence of a substitution in the EC-SOD gene at the heparin-binding domain could be a prognostic marker of dialysis patients.

Cause of Death↗
PubMed2000

Lack of association between duration of untreated illness and severity of cognitive and structural brain deficits at the first episode of schizophrenia.

OBJECTIVE: The purpose of the study was to determine whether the duration of illness before antipsychotic drug treatment for schizophrenia was associated with the severity of cognitive deficits and volumetric brain structure anomalies observed in some patients with a first episode of schizophrenia. METHOD: Duration of psychotic symptoms and of other symptoms marking a behavioral change was estimated from structured interviews with 50 patients who had a first episode of schizophrenia and their family members. Interviews were conducted within a month of the patients' hospitalization. Duration of untreated psychotic symptoms and of behavioral change was correlated with neuropsychological summary scores from a comprehensive cognitive battery and with measurements of lateral ventricular, temporal lobe, and cerebral hemispheric volumes. RESULTS: No significant correlations were observed between measures of untreated illness and the severity of either cognitive or structural brain deficits at baseline. CONCLUSIONS: The duration of untreated symptoms of schizophrenia, for which an association with an uncontrolled toxic brain process has been proposed, is unlikely to explain why first-episode patients with schizophrenia have widespread deficits in cognitive functioning and have detectable ventricular enlargement and some loss of cortical mass.

Adult↗
PubMed2000

Clinical features and predictors of in-hospital mortality in patients with acute and chronic pulmonary thromboembolism.

OBJECTIVE: The differences in the clinical findings of patients with acute pulmonary thromboembolism (acute-PTE) and chronic pulmonary thromboembolism (chronic-PTE) were compared, and the association between the clinical findings and prognosis in the two groups was analyzed. PATIENTS: This study included 204 patients with PTE, 139 patients with acute-PTE and 65 patients with chronic-PTE. RESULTS: There were significant differences between acute-PTE and chronic-PTE in the predisposing factors of post operation (19.4 versus 1.5%, p = 0.0003), and electrocardiographic signs such as sinus tachycardia (73.7 versus 50.9 %, p = 0.007), ST-depression (25.3 versus 9.4%, p = 0.03), right ventricular hypertrophy (20.0 versus 47.2%, p = 0.0007), and right axis deviation (3.2 versus 22.6%, p = 0.0003). Thirty-one of the 139 acute-PTE patients died from PTE, as did 17 of the 65 chronic-PTE patients. The prognosis was poor in patients older than 70 years old (p = 0.01), with stroke (p = 0.008), syncope (p = 0.01), shock (p = 0.0006), hypocapnia (PaCO2 < or = 25 torr; p = 0.0006) and an elevation in total pulmonary resistance (TPR >1,000 dyne-sec cm(-5) (p = 0.02)) in acute-PTE, and in those with syncope (p = 0.03), shock (p = 0.008), and right ventricular hypertrophy on electrocardiogram (p = 0.03) in chronic-PTE. CONCLUSION: The results of this study indicate a relationship between the clinical features of patients with acute-PTE and chronic-PTE, and the predictors of in-hospital mortality.

Acute Disease↗
PubMed2000

Surgical results of Stanford type B aortic dissection. Comparisons between partial and subtotal replacement of the dissected aorta.

BACKGROUND: Surgical results for Stanford type B aortic dissection were retrospectively compared between the subtotal prosthetic replacement of the thoracoabdominal dissected aorta (STR) and partial replacement of the descending aorta at the intimal tear (PR). METHODS: Twenty-two patients (11 males and 11 females with mean age of 56.9+/-2.6 years) undergoing repair of aneurysms were analyzed. All operations were performed with the aid of femorofemoral partial cardiopulmonary bypass. Reconstruction of the critical artery for spinal cord blood supply was determined by evoked spinal cord potential (ESP) monitoring in non-urgent cases. Operative mortality and incidence of complications were compared between the PR group (Group I; n=15) and the STR group (Group II; n=7). RESULTS: There were one operative death and one late death in Group I. No early or late deaths occurred in Group II. Postoperative paraplegia occurred in 1 patient in Group I and 2 patients in Group II. Among patients undergoing selective reconstruction of the critical intercostal arteries, paraplegia occurred in only one patient. Incidence of postoperative complications was not significantly different between Group I and Group II. Presence of rupture (p<0.001) and development of acute renal failure (p<0.05) revealed significant determinants of postoperative mortality by multivariate analysis. Operative procedure did not influence postoperative mortality or occurrence of paraplegia. CONCLUSIONS: Operative results of STR with selective reconstruction of the critical arteries and PR for aortic dissection were comparable. Subtotal replacement of the thoracoabdominal dissected aorta is encouraged to apply for patients with diffuse, large postdissection aneurysms or those with a high risk of future enlargement of remaining false channels such as Marfan syndrome, under adequate reconstruction of the critical segmental arteries.

Acute Kidney Injury↗