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Biomedical subjects

Y Takemura

Publications and source records attributed to Y Takemura.

At least 37 records · Page 2Linked to original sources

Laboratory testing under managed care dominance in the USA.

The uncontrolled escalation of total health care expenditure despite the government's endeavours during the past decades in the USA had led to the rapid infiltration of managed care organisations (MCOs). Traditional hospital based laboratories have been placed in a crucial situation with the advent of the managed care era. A massive reduction of in house testing urged them to develop strategies against financial difficulty. Consolidation and networking, participation in the outreach testing market, and emphasis on point of care/satellite laboratory testing in non-traditional, ambulatory settings are major strategies for the survival of hospital laboratories. Several physicians' office laboratories (POLS) have closed their doors in response both to regulatory restrictions imposed by the Clinical Laboratory Improvement Amendments of 1988 and to managed care infiltration. It seems likely that POLs and hospital laboratories will continue to reduce test volumes, whereas commercial reference laboratories will thrive through contracting with MCOs. In the current climate of managed care dominance in the USA, clinical laboratories are changing their basic operation focus and mission in response to the aggressively changing landscape.

Humans↗

[Validity of reticulocyte count testing in reimbursement practice: a cost-effectiveness analysis].

Recently reticulocyte count testing has markedly decreased in Japan. We studied the current status of the reduction of reimbursement for reticulocyte count testing and the cost-effectiveness of the test in an academic hospital. The orders of complete blood counts(CBC) accompanied by reticulocyte count testing in Tokai University Hospital declined from 58.9 to 13.3% during the last decade. Among a total of 15,538 test orders for reticulocyte count in outpatients, full reimbursement was refused in 123(0.79%) during a one year period from April 1999 to March 2000. The cost-effectiveness of reticulocyte count testing was evaluated in 719 new outpatients who visited Tokai University Hospital during this period. A useful result(UR) of testing was defined as that which contributed to a change in a physician's diagnosis- or decision-making, relating to a "tentative initial diagnosis" obtained from patient history and physical examination alone. Cost-effectiveness for either CBC alone or in combination with reticulocyte count testing was evaluated by calculating clinical effectiveness(the number of URs yielded by a test per patient), economic efficiency(cost required for a test per UR generated), and the cost-effectiveness values(cost required for additional test(s) per additional UR generated). There was a wide disparity in the clinical effectiveness of reticulocyte count twisting among the hospital departments, ranging from 0.53 UR/patient(Gastroenterology-2) to 0(Oral Surgery, Neurology, Urology). Poor clinical effectiveness shown in particular hospital departments endorsed the increasing percentages in reimbursement rejection by the payer of health insurance. The test should be ordered more carefully in consideration of reimbursement and in regard to its cost-effectiveness among different patients groups.

Cost-Benefit Analysis↗

[Aggressively metastatic neuroendocrine carcinoma in the middle mediastinum].

A 50-year-old male patient with no symptoms was admitted to our hospital for further evaluation of a right superior mediastinal mass shadow found in chest radiographs during a health examination. Computed tomographic (CT) scans demonstrated a middle mediastinal mass of 4 cm in diameter surrounded by the SVC, the ascending aorta and the trachea at the subaortic level. Routine examination disclosed no metastatic or primary lesion elsewhere. A surgical biopsy resulted in a diagnosis of neuroendocrine carcinoma of unknown primary organ. The patient was given 1 course of chemotherapy with CAV-PE, but little effect was seen. However, when a PE regimen combined with thoracic radiation was used, the tumor shrank to half of its size. After the patient subsequently received high-dose treatment with Etoposide, CT imaging and cytologic analysis revealed multiple metastases to the subcutaneous tissue, both adrenal glands and the liver. Lung lesions also spread aggressively, and the patient died of metastasis. Although neuroendocrine carcinomas can arise from the systemic neuroendocrine cells including those in the mediastinum, their appearance in the middle mediastinum is rarely reported.

Adrenal Cortex Neoplasms↗

[A systematic review for the diagnostic accuracy o serum C-reactive protein measurement in neonatal infants with infection].

We presented an example of systematic review regarding diagnostic test accuracy. We compared the diagnostic accuracy of serum C-reactive protein (CRP) concentrations measured by the highly sensitive methods for neonatal infection with that by the conventional-sensitivity methods in the literatures available. Our results with the summary ROC curve indicated that the high sensitivity CRP is likely to provide a better diagnostic accuracy than the conventional methods, even though there was a heterogeneity in the specificity among studies. In the reviewing process of the literatures, we found several critical problems, such as the publishing bias and insufficient quality of primary articles. These problems may have had a substantial influence on the summary estimates. Systematic reviewing of the related articles uncovered the defects in the primary studies, requiring more prudent study designs for future clinical trials.

Algorithms↗

Novel approaches to reversing anti-cancer drug resistance using gene-specific therapeutics.

One of the underlying mechanisms of multidrug resistance (MDR) is cellular overproduction of P-glycoprotein (P-gp), which acts as an efflux pump for various anti-cancer drugs. P-gp is encoded by a group of related genes termed MDR; only MDR1 is known to confer the drug resistance, and its overexpression in cancer cells has been a therapeutic target to circumvent the resistance. To overcome P-gp-mediated drug resistance, we have developed six anti-MDR1 hammerhead ribozymes and delivered them to P-gp-overproducing human leukemia cell line by a retroviral vector containing RNA polymerase III promoter. These ribozyme-transduced cells became vincristine-sensitive, concomitant with the decreases in MDR1 expression, P-gp amount and efflux pump function. Among the ribozymes tested, the anti-MDR1 ribozyme against the translation-initiation site exhibited the highest efficacy. The retrovirus-mediated transfer of this most potent anti-MDR1 ribozyme into a human lymphoma cell line, which was made resistant by infection of pHaMDR1/A retroviral vector and thus possessed a low degree of MDR due to P-gp expression relevant to clinical MDR, resulted in a complete reversal of MDR phenotype. In addition to retrovirus-mediated transfer of ribozymes, we evaluated the efficacy of cationic liposome-mediated transfer of ribozyme. Treatment of a P-gp-producing human breast cancer cell line with the liposome-ribozyme complex resulted in reversal of resistance, concomitant with the decreases in both MDR1 expression and P-gp amount. Confocal microscopic imaging of the cells after treatment with liposome/FITC-dextran showed cytoplasmic fluorescence that was abolished by cytochalasin B, indicating a high endocytotic activity in these cells. The endocytotic activity was well correlated with the success of cationic liposome-mediated transfer of MDR1 ribozyme. These distinct approaches using either retrovirus- or liposome-mediated transfer of anti-MDR1 ribozyme may be selectively applicable to the treatment of MDR cells with different properties such as endocytotic activity as a specific means to reverse resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Antifolate resistance and its circumvention by new analogues.

We have established human leukemia cell lines made resistant to various antifolate drugs and analyzed resistance mechanisms developed in these cells at the cellular and molecular levels. The cells acquired resistance to antifolate drug(s) through: (1) impaired drug uptake via the reduced folate carrier, (2) increased activity of the target enzymes[dihydrofolate reductase(DHFR) or thymidylate synthase(TS)] resulted from a concomitant amplification and overexpression of their gene, (3) induction of a variant DHFR with a low affinity for antifolate drug(s) used for the selection of resistance, and (4) defective polyglutamation. Each resistance mechanism was not necessarily induced at random, but appeared to relate to the biochemical and pharmacological properties of the drug exposed, biological dispositions of the cells, drug-exposure manners to, or culture conditions of the cells. Since it has been shown that a minor modification at the specified position of the folate structure resulted in a drastic change in its pharmacological properties, many new compounds have been rationally designed on the basis of the knowledge of relationships between structure modifications and pharmacological properties. The step-by-step approach to the development of new analogues led to the discoveries of several promising antifolate drugs such as trimetrexate and raltitrexed, which can overcome the acquired and natural resistance to methotrexate, a classical antifolate, and clinical trials of these newer classes of antifolate compounds are currently underway.

Carrier Proteins↗

Inhibitory effect of flavonoids from citrus plants on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

To search for possible anti-tumor promoters, thirteen flavones (1-13) obtained from the peel of Citrus plants were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these flavones, 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT) (13) exhibited significant inhibitory effects on the EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, compound 13 exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

Animals↗

Serum concentrations of advanced glycation endproducts are associated with the development of atherosclerosis as well as diabetic microangiopathy in patients with type 2 diabetes.

We measured serum concentrations of advanced glycation endproducts (AGEs) in patients with type 2 diabetes, to elucidate the mechanisms underlying the elevated serum concentrations of AGEs and to clarify the relationship between serum AGE concentrations and the development of microangiopathy and macroangiopathy. Serum AGEs were significantly higher in diabetic patients than in age-matched control subjects (p < 0.0001). In diabetic patients, serum AGEs were positively correlated with HbAlc (r = 0.47, p < 0.0001), urinary albumin excretion (UAE) (r = 0.42, p < 0.0001), diabetes duration (r = 0.31, p = 0.0030), and fasting plasma glucose (r = 0.34, p = 0.0010). Multiple regression analysis disclosed that only the HbAlc and UAE levels independently correlated with serum AGE levels. Serum AGEs in diabetic patients with progressive retinopathy and overt nephropathy were significantly higher than in those with less severe retinopathy and nephropathy. Serum AGEs were significantly higher in the diabetic patients with coronary heart disease (CHD) than in those without CHD. These results suggest that the HbAlc and UAE levels are independent risk factors for increased serum AGE concentrations in type 2 diabetic patients, and that higher serum AGE concentrations are associated with increased severity of diabetic retinopathy and nephropathy. Serum AGE concentrations may be a useful marker not only for the severity of diabetic microangiopathy but also for the development of CHD in patients with type 2 diabetes mellitus.

Aged↗

Relationship between soluble thrombomodulin in plasma and coagulation or fibrinolysis in type 2 diabetes.

Serum concentration of soluble thrombomodulin (TM) is thought to be a marker for endothelial damage. Although several studies have reported that serum TM concentrations are increased in patients with diabetes mellitus, there is little information on the physiological function of soluble TM in human plasma. To evaluate the relationship of soluble TM in plasma between coagulation and/or fibrinolysis system in patients with diabetes, we measured plasma soluble TM, protein C activity (a natural anticoagulant induced by thrombin-TM complex), prothrombin F1+2 (a direct marker of thrombin generation), and plasmin-alpha 2-antiplasmin complex (PAP) and D dimer (measures of fibrinolytic activity) in 55 patients with type 2 diabetes mellitus. The plasma concentrations of soluble TM (P<0.01), protein C activity (P<0.01), prothrombin F1+2 (P<0.05), PAP (P<0.001) and D dimer (P<0.001) were significantly higher in the diabetic patients than the 48 age-matched control subjects. The plasma concentrations of TM and PAP were obviously increased in patients with diabetic nephropathy. In the diabetic patients, the plasma concentrations of soluble TM were inversely correlated with the protein C activity (r=-0.43, P<0.005), and were positively correlated with the plasma concentrations of prothrombin F1+2 (r=0.63, P<0.0001) and the plasma PAP concentrations (r=0.30, P<0.05). The present study demonstrated that both coagulation and fibrinolysis are enhanced concomitantly in patients with type 2 diabetes mellitus, and that an increase in plasma concentration of soluble TM is associated not only with hypercoagulability but also with enhanced fibrinolysis in diabetic patients.

Adult↗

Artificial insemination using cryopreserved sperm in the silkworm, Bombyx mori.

We report in this paper that female moths artificially inseminated with cryopreserved sperm (-196 degrees C) could oviposit eggs when the sperm was preserved for 356days, and that the fertilization rate and the number of eggs laid were almost equivalent to those obtained in normally mated moths. The optimal cooling rate for sperm freezing was 5-65 degrees C/min for maintaining a high fertility of sperm. The simple and reliable method of cryopreservation was to put the semen first in a deep freezer at -80 degrees C and thereafter put them in liquid nitrogen. When female moths of 'white 2' egg-color mutant strain were inseminated with a mixture of frozen-thawed sperm from males of normal-colored egg strain and non-frozen sperm from males of the 'white 2', female moths deposited a majority of 'white 2' eggs and a very small number of eggs of normal color. The result shows that there was a competitive fertilization of sperm between the two strains of the silkworm, and that sperm fertility was reduced to a considerable extent by freezing at -196 degrees C. These results may contribute not only to basic studies on fertilization in Lepidoptera but also to the development of long-term preservation procedure of genetic resources by using cryopreserved sperm of Bombyx mori.

Journal Article↗

Serum levels of carboxy-terminal propeptide of human type I procollagen are an indicator for the progression of diabetic nephropathy in patients with type 2 diabetes mellitus.

The finding that glomerular mesangial cells produce human type I collagen suggests that the serum levels of carboxy-terminal propeptide of human type I procollagen (P1CP) may reflect the severity of diabetic nephropathy. We therefore investigated the relationship between serum P1CP levels and the extent of diabetic complications in 100 patients (46 males and 54 females) with Type 2 diabetes and in 64 healthy subjects. Serum P1CP was determined by radioimmunoassay. In diabetes, we defined P1CP levels less than 142 ng/ml as a normal P1CP group (group A), whereas we defined them as equal to or greater than 142 ng/ml as a high P1CP group (group B). The diabetic patients had significantly elevated serum P1CP levels compared with the controls. The prevalence of hypertension, proliferative diabetic retinopathy or macroalbuminuria was significantly higher in group B than in group A. Serum P1CP levels showed a significant positive correlation with urinary albumin excretion, but not with fasting blood glucose, glycosylated hemoglobin A(1c) or serum osteocalcin. Macroalbuminuric patients showed significantly higher P1CP levels than the normoalbuminuric patients. In patients in the absence of diabetic nephropathy, no significant differences of P1CP levels were found among the severity of diabetic retinopathy. The present results suggest that serum P1CP levels reflect the progression of diabetic nephropathy in patients with Type 2 diabetes.

Biomarkers↗

Thermographic measurement of skin temperature recovery time of extremities in patients with type 2 diabetes mellitus.

To elucidate the relationship between the recovery of skin temperature in an extremity after exposure to cold water and various factors associated with diabetes, we measured skin temperature in type2 diabetic patients (N=61) and control subjects (N=16). A thermo-tracer was used in thermographic measurements. The right third toe of each subject was immersed in cold water at 0 degrees C for 10 sec. Rt represents the recovery rate of skin temperature at t min after exposure. Rt was significantly reduced in the diabetic patients every 5 min in the 20 min period following exposure compared with control subjects. The diabetic patients group exhibited a significantly positive correlation between R20 and the ankle-brachial index. R20 in the diabetic patients showed a significantly positive correlation with the reduction in systolic blood pressure at the arm observed in Schellong's test. In addition, R20 showed a significantly negative correlation with plasma levels of fibrinogen and plasminogen activator inhibitor-1. However, the severity of diabetic retinopathy and nephropathy was not significantly related to R20 in the diabetic patients. The present data indicate that the recovery of skin temperature after immersion in cold water was markedly reduced in patients with type 2 diabetes mellitus as compared with healthy control subjects. Peripheral arteriosclerosis, impaired sympathetic nerve function and the activation of the blood coagulation system may all contribute to this reduced recovery of skin temperature.

Analysis of Variance↗

Competitive reverse transcription-polymerase chain reaction assay for quantification of human multidrug resistance 1 (MDR1) gene expression in fresh leukemic cells.

We have analyzed MDR1 gene expression in 69 clinical samples obtained from 64 patients with leukemic hematologic malignancies by using a competitive reverse transcription-polymerase chain reaction assay with a heterologous competitor RNA. To exclude a false-positive result caused by concomitant normal lymphocytes that physiologically express MDR1, in samples we determined a cut-off value of 8 amol MDR1 transcript per microgram of RNA by simultaneous measurement of rhodamine 123 dye efflux either in lymphocyte or gated leukemic cell populations. Consequently, 23 of 69 samples were concluded to be MDR1-positive in leukemic cells per se. The MDR1 expression rate was significantly correlated with factors such as a history of preceding chemotherapy, elder age of the patient, and certain disease types (eg, leukemia progressed from myelodysplastic syndrome). Moreover, the complete response rate after chemotherapy was significantly higher in MDR1-negative patients than in MDR1-positive patients (52% vs 17%, respectively; P = .01). The assay established will enable the quantification of MDR1 gene expression in blood samples from patients with leukemic hematologic malignancies and will be applicable to clinical laboratories as a routine test.

Adolescent↗

Four new furanone-coumarins from Clausena excavata.

Four new furanone-coumarins, clauslactones-N (4), -O (5), -P (6) and -Q (7) were isolated from the leaves and twigs of Clausena excavata BURM. f. (Rutaceae) collected in Indonesia and their structures were elucidated by spectroscopic analysis.

4-Butyrolactone↗

A cross-sectional study on the relationship between leisure or recreational physical activity and coronary risk factors.

Several researchers have investigated the relationship between physical activity and coronary risk factors. Little is known about the strength of the relationship between physical activity and each coronary risk factor. The aim of this study is to determined the strength of the relationship between leisure or recreational physical activity and selected coronary risk factors. The subjects were 781 male Japanese office workers who underwent an annual physical examination in 1999, including interview about the type and frequency of their leisure or recreational physical activities, other lifestyle questionnaire, and biological measurement, calculated a physical activity index (PAI) for each subject. To investigate the strength of the relationship between PAI and each coronary risk factor, we carried out multiple regression analysis. Smoking habit, log triglycerides, self-rating depression scale (SDS) score, alcohol habit and left ventricular hypertrophy were significantly related to the physical activity (partial R2: 0.031, 0.018, 0.016, 0.0092, 0.0075, respectively). Smoking habit was the strongest determinant of the physical activity. Furthermore, we found the inverse relationship between SDS score and physical activity independently.

Alcohol Drinking↗

A high level of physical fitness during thirties is a negative risk factor for colonic polyps during fifties.

This case-control study examined the relationship between the occurrence of colonic polyps in men in their fifties and the level of their physical fitness while in their thirties. The subjects consisted of 51 male Japan Self-Defense Forces officials in their fifties who had colonic polyps, as diagnosed by colonoscopic examination, and 46 control individuals. As an indicator of physical fitness between 30 and 39, we selected the best time recorded for each individual during that decade of life for the 1,500 meter Physical Fitness Test run. We calculated the odds ratio for polyps according to selected risk factors (including physical fitness), and a logistic regression analysis was used to adjust for possible confounding variables. Odds ratio (95% confidence interval, p value) for colonic polyps with physical fitness in the thirties was 0.36 (0.16-0.82, p < 0.05). With adjustment for the subjects' maximum Body Mass Index in both their thirties and fifties, and serum total cholesterol, the odds ratio was 0.39 (0.15-0.99, p < 0.05). We suggest that the occurrence of colonic polyps in men in their fifties can be reduced by maintaining a high level of physical fitness while in their thirties.

Adult↗

[Regional differences of in vivo proton MR spectroscopy in developing human brain].

The purpose of this study was to clarify regional differences in proton MR spectroscopy (1H-MRS) in the developing human brain. Proton MR spectra were obtained from 24 infants aged 0 to 24 months old. Proton MR spectroscopy was performed on a 1.5 Tesla clinical MR unit using a 3D-chemical shift imaging sequence (3D-CSI). MR spectra obtained from voxels in frontal white matter and those in parietal white matter were compared. The NAA/Cho ratios of the frontal region were lower than those of the parietal region at birth but increased rapidly during the first six months of life. The rate of increase was reduced in the second year of life. In contrast, NAA/Cho ratios in paracentral areas were already high at birth but increased slowly through the first two years of life. Cho/Cr ratios of the frontal region were stable during the first year of life and started to decrease in the second year of life. In the parietal region, Cho/Cr ratios were decreased throughout infancy. Regional differences in 1H-MRS spectra were apparent during infancy, and these differences were suggested to reflect regional differences in the maturation of the developing human brain.

Adult↗