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Biomedical subjects

M Emoto

Publications and source records attributed to M Emoto.

At least 37 records · Page 2Linked to original sources
PubMed2001

Impact of insulin resistance and nephropathy on homocysteine in type 2 diabetes.

OBJECTIVE: To assess the impacts of insulin resistance and renal function on plasma total homocysteine (tHcy) levels in patients with type 2 diabetes with a wide range of nephropathy. RESEARCH DESIGN AND METHODS: Plasma tHcy levels were measured using the enzyme immunoassay method in 75 patients with type 2 diabetes and compared with those in 54 healthy control subjects. Insulin sensitivity indexes were assessed in patients with type 2 diabetes by hyperinsulinemic-euglycemic clamp using artificial pancreas. RESULTS: Plasma tHcy levels and their log-translormed values (log tHcy) were significantly higher in all patients with diabetes than in control subjects (tHcy, 12.0 +/- 0.7 [SE] vs. 8.7 +/- 0.3 micromol/l, P < 0.0001; log tHcy, 1.040 +/- 0.021 vs. 0.920 +/- 0.016 micromol/l, P < 0.0001). Plasma tHcy levels in patients with diabetes were significantly increased according to degree of nephropathy (P < 0.0001). On simple regression analyses, log tHcy correlated with insulin sensitivity indexes (r = -0.319, P = 0.005) as well as creatinine clearance (r = 0.634, P < 0.0001) in all patients with diabetes. Multiple regression analyses showed that insulin sensitivity indexes (beta = -0.245) as well as creatinine clearance were independent contributors to log tHcy in all patients with diabetes (R2 = 0.750, P < 0.0001). For the 59 patients with diabetes with creatinine clearance >60 ml/min, insulin sensitivity indexes were also shown to be a significant contributor to log tHcy (beta = -0.438, R2 = 0.561, P < 0.001). CONCLUSION: Insulin resistance and renal function are independent determinants of tHcy levels in patients with type 2 diabetes.

Blood Glucose↗
PubMed2001

Glycemic control is a predictor of survival for diabetic patients on hemodialysis.

OBJECTIVE: To investigate the impact of glycemic control on the survival of diabetic subjects with end-stage renal disease (ESRD) starting hemodialysis treatment. RESEARCH DESIGN AND METHODS: This single-center prospective observational study enrolled 150 diabetic ESRD subjects (109 men and 41 women; age at hemodialysis initiation, 60.5 +/- 10.2 years) at start of hemodialysis between January 1989 and December 1997. The subjects were divided into groups according to their glycemic control level at inclusion as follows: good HbA1c <7.5%, n = 93 (group G), and poor HbA1c > or = 7.5%, n = 57 (group P); and survival was followed until December 1999, with a mean follow-up period of 2.7 years. RESULTS: Group G had better survival than group P (the control group) (P = 0.008). At inclusion, there was no significant difference in age, sex, systolic blood pressure (SBP), BMI, cardio-to-thoracic ratio (CTR) on chest X-ray, and serum creatinine (Cre) or hemoglobin (Hb) levels between the two groups. After adjustment for age and sex, HbA1c was a significant predictor of survival (hazard ratio 1. 133 per 1.0% increment of HbA1c, 95% CI 1.028-1.249, P = 0.012), as were Cre and CTR. CONCLUSIONS: Good glycemic control (HbA1c <7.5%) predicts better survival of diabetic ESRD patients starting hemodialysis treatment.

Blood Glucose↗
PubMed2001

Relations between ACE gene and ecNOS gene polymorphisms and resistive index in type 2 diabetic patients with nephropathy.

OBJECTIVE: ACE and endothelial cell nitric oxide synthase (ecNOS) genotypes have been reported to be related to the incidence of renal diseases and coronary artery diseases. In order to assess the effect of the gene polymorphism of both ACE and ecNOS on renal hemodynamic abnormality, we examined 155 Japanese patients with type 2 diabetes with various stages of nephropathy. RESEARCH DESIGN AND METHODS: The patients ranged in age from 40 to 72 years (92 men and 63 women). They were divided into four groups: group 1 consisted of patients with urinary albumin excretion (UAE) <30 mg/day (n = 69), group 2 had 30 < or = UAE < 300 mg/day (n = 44), group 3 had UAE > or =300 mg/day and serum creatinine <1.5 mg/dl (n = 22), and group 4 had serum creatinine >1.5 mg/dl (n = 20). Intrarenal hemodynamics were studied by duplex Doppler sonography in patients with type 2 diabetes. The ACE and ecNOS gene polymorphisms were examined by polymerase chain reaction. RESULTS: There were no significant differences in sex, BMI, and blood glucose level, but there were differences in HbA(1c) and lipoprotein profiles among the four groups. There were no significant differences in the distribution of ACE genotype or in the frequency of the ecNOS 4a allele among the four groups. Resistive index (RI) values of the interlobar arteries of group 4 were significantly higher than those of groups 1, 2, and 3, whereas the RI values were not significantly different among groups 1, 2, and 3. Multiple regression analysis showed that age, duration of diabetes, systolic and diastolic blood pressure, and creatinine clearance were significantly associated with the increased RI values, but that there was no significant association between RI values and the ecNOS genotype (R(2) = 0.613, P < 0.0001). CONCLUSIONS: These results suggest that intrarenal hemodynamic abnormalities are present as a feature of the progression of nephropathy in type 2 diabetes, and that they are associated with age, duration of diabetes, decreased creatinine clearance, and blood pressure, but not with the genetic factors of the ACE and ecNOS gene polymorphism in nephropathy of type 2 diabetes.

Adult↗
PubMed2000

Perinuclear localization and insulin responsiveness of GLUT4 requires cytoskeletal integrity in 3T3-L1 adipocytes.

The GLUT4 glucose transporter resides mostly in perinuclear membranes in unstimulated 3T3-L1 adipocytes and is acutely translocated to the cell surface in response to insulin. Using a novel method to purify intracellular GLUT4-enriched membranes, we identified by mass spectrometry the intermediate filament protein vimentin and the microtubule protein alpha-tubulin as components of these membranes. Immunoelectron microscopy of the GLUT4-containing membranes also revealed their association with these cytoskeletal proteins. Disruption of intermediate filaments and microtubules in 3T3-L1 adipocytes by microinjection of a vimentin-derived peptide of the helix initiation 1A domain caused marked dispersion of perinuclear GLUT4 to peripheral regions of the cells. Inhibition of the microtubule-based motor dynein by brief cytoplasmic acidification of cultured adipocytes also dispersed perinuclear GLUT4 and inhibited insulin-stimulated GLUT4 translocation to the cell surface. Insulin sensitivity was restored as GLUT4 was again concentrated near the nucleus upon recovery of cells in physiological buffer. These data suggest that GLUT4 trafficking to perinuclear membranes of cultured adipocytes is directed by dynein and is required for optimal GLUT4 regulation by insulin.

3T3 Cells↗
PubMed2000

Ion heating and high-energy-particle production by ion-cyclotron heating in the large helical device

Ion-cyclotron heating was applied to the Large Helical Device. When the proton-cyclotron resonance was near the saddle point of the magnetic field-strength plane, strong ion-cyclotron damping occurred. Under these conditions efficient plasma heating was achieved for more than one minute. A high-energy ion tail was observed, and the effective tail temperature was determined by a balance between the wave acceleration and the electron-drag relaxation. There was no apparent sign of particle orbit loss effect in the investigated density range of 0.8-1.3x10(19) m(-3).

Journal Article↗
PubMed2000

Cutting edge: contribution of NK cells to the homing of thymic CD4+NKT cells to the liver.

In contrast to peripheral lymphoid organs, in the liver a high proportion of T cells are CD4+NKT cells. We have previously reported that LFA-1 plays a pivotal role in the homing of thymic CD4+NKT cells to the liver. In the present study, we further assessed which cell type participates in the homing of thymic CD4+NKT cells to the liver. The accumulation of donor thymocyte-derived CD4+NKT cells in the liver of SCID mice that had been reconstituted with thymocytes from C57BL/6 mice was severely impaired by in vivo depletion of NK cells, but not Kupffer cells in recipients. These results suggest that NK cells participate in the homing of thymic CD4+NKT cells to the liver. We assume that LFA-1 expressed on NK cells is involved in this mechanism.

Animals↗
PubMed2000

Transvaginal color Doppler ultrasonic characterization of benign and malignant ovarian cystic teratomas and comparison with serum squamous cell carcinoma antigen.

BACKGROUND: The preoperative diagnosis of squamous cell carcinoma (SCC) arising in mature cystic teratoma of the ovary remains difficult. The purpose of this study is to examine the usefulness of transvaginal color Doppler ultrasound (TV-CDU) in differentiating malignant (SCC) from benign cystic teratoma of the ovary. METHODS: Eighty-eight patients with an ovarian tumor showing gray scale sonographic appearances of mature cystic teratoma were preoperatively evaluated for the presence or absence of intratumoral blood flow by TV-CDU. The blood flow characteristics of the tumor vessels were analyzed using the resistance index (RI), pulsatility index (PI), and peak systolic velocity (PSV). The serum levels of SCC antigen were also randomly examined preoperatively in 50 patients. RESULTS: Intratumoral blood flow was significantly detected in malignant teratomas (SCCs) (80.0%; 4 of 5) compared with benign teratomas (20.5%; 17 of 83) (P < 0.01). All malignant teratomas with intratumoral blood flow showed both RI less than 0.4 and PI less than 0.6, whereas no benign teratomas showed any such value except for 1 case with struma ovarii. In addition, both the mean RI and the mean PI values in the tumor vessels were significantly lower in the malignant teratomas (RI: 0.31 +/- 0.07; PI: 0.40 +/- 0.16) than in the benign teratomas (RI: 0.62 +/- 0.13; PI: 1.06 +/- 0.44) (P < 0.001). However, the mean PSV value of the malignant teratomas (PSV: 20.6 +/- 8.33) was not significantly different from the benign teratomas (PSV: 18.1 +/- 9.9). Elevation of serum SCC was found in 4 of 5 patients (80%) with malignant teratomas, whereas the elevation was found in 11 of 45 patients (24.4%) with benign teratomas (P < 0.05). The diagnostic accuracy using the RI (cutoff value 0.4) as well as the PI (cutoff value 0.6) was thus 95.2%, which was significantly superior to that obtained by using the serum SCC (76%) (cutoff value, 1.5 ng/mL). CONCLUSIONS: Evaluating the presence or absence of intratumoral blood flow, together with blood flow resistance, in tumor vessels using TV-CDU thus may be more useful to differentiate malignant (SCC) from benign cystic teratomas of the ovary than by measuring serum SCC levels.

Adult↗
PubMed2000

A role for phospholipase D in GLUT4 glucose transporter translocation.

Based on recent studies showing that phospholipase D (PLD)1 is associated with intracellular membranes and promotes membrane budding from the trans-Golgi, we tested its possible role in the membrane trafficking of GLUT4 glucose transporters. Using immunofluorescence confocal microscopy, expressed Myc epitope-tagged PLD1 was found to associate with intracellular vesicular structures by a mechanism that requires its N-terminal pleckstrin homology domain. Partial co-localization with expressed GLUT4 fused to green fluorescent protein in both 3T3-L1 adipocytes and Chinese hamster ovary cells was evident. Furthermore, microinjection of purified PLD into cultured adipocytes markedly potentiated the effect of a submaximal concentration of insulin to stimulate GLUT4 translocation to cell surface membranes. Insulin stimulated PLD activity in cells expressing high levels of insulin receptors but no such insulin effect was detected in 3T3-L1 adipocytes. Taken together, these results are consistent with the hypothesis that PLD1 associated with GLUT4-containing membranes acts in a constitutive manner to promote the mechanism of GLUT4 translocation by insulin.

3T3 Cells↗
PubMed2000

Edge thermal transport barrier In LHD discharges

In LHD discharges a significant enhancement of the global energy confinement has been achieved for the first time in a helical device with an edge thermal barrier, which exhibits a sharp gradient at the edge of the temperature profile. Key features associated with the barrier are quite different from those seen in tokamaks: (i) almost no change in particle (including impurity) transport, (ii) a gradual formation of the barrier, (iii) a very high ratio of the edge temperature to the average temperature, and (iv) no edge relaxation phenomenon. These features are very attractive in applying the thermal barrier to future reactor grade devices.

Journal Article↗
PubMed2000

Phenotypic characterization of CD8(+)NKT cells.

We describe a novel CD8(+)NKT cell population expressing TCRalpha /beta or TCRgamma /delta. These CD8(+)NKT cells were prominent in the liver, and except for the thymus, virtually absent in other lymphoid organs. CD8(+)NKT cells expressed activation markers and comprised a high proportion of Ly49(+) cells. The development of the majority of CD8(+)NKT cells expressing TCRalpha /beta, but not TCRgamma /delta, depended on classical MHC class I. No CD8(+)NKT cells were detectable in young athymic mice, whereas the cells expressing TCRgamma /delta, but not TCRalpha /beta, appeared randomly in aged athymic mice. CD8(+)NK1(+) TCRalpha /beta cells showed polyclonal TCRVbeta usage and were virtually devoid of TCRValpha14. CD8(+)NK1(+) TCRgamma /delta cells predominantly expressed TCRVgamma1, 2 and 4, and Vdelta4, 5, 6 and 7. CD8(+)NKT cells, in particular those expressing TCRgamma /delta, were a major population in early life. IFN-gamma, but not IL-4, was induced in CD8(+)NKT cells by in vitro stimulation, independent of the TCRalpha /beta or TCRgamma /delta lineage. Hence, these cells represent a unique, though heterogeneous T cell population that shares markers with, but is distinct from, both conventional NKT cells and conventional CD8(+) T cells, and that may play a role in immune regulation.

Animals↗
PubMed2000

Participation of leukocyte function-associated antigen-1 and NK cells in the homing of thymic CD8+NKT cells to the liver.

A distinct CD8+NKT cell population expressing TCRalpha/beta or TCRgamma/delta has been identified in liver and thymus. We wondered whether cell adhesion molecules play a role in the homing of CD8+NKT cells to the liver. The number of liver CD8+NKT cells was markedly reduced in leukocyte function-associated antigen (LFA)-1-/- mice compared with wild-type (WT) mice. The reduction was restricted to the liver only and no measurable alterations were found in other organs. In the liver of SCID mice reconstituted with thymocytes from LFA-1-/- or WT mice, the number of donor-derived CD8+NKT cells was comparable and the vast majority of these cells expressed TCRalpha/beta. In a reciprocal radiation thymocyte reconstitution system with LFA-1-/- and WT mice, LFA-1 expressed on liver cells other than CD8+NKT cells appeared to be required for the homing of thymic CD8+NKT cells to the liver. The accumulation of donor thymocyte-derived CD8+NKT cells in the liver of SCID mice was severely impaired by in vivo depletion of NK cells, but not of Kupffer cells. These results not only indicate that thymus provides a source for CD8+NKT cells expressing TCRalpha/beta in the liver, but also suggest that LFA-1 expressed on NK cells is involved in the homing of thymic CD8+NKT cells to the liver.

Animals↗
PubMed2000

Inverse relationship between circulating oxidized low density lipoprotein (oxLDL) and anti-oxLDL antibody levels in healthy subjects.

Oxidized low density lipoprotein (oxLDL) has been implicated in the pathogenesis of atherosclerosis. Recent studies have shown that immunization of animals with oxLDL results in suppression of atherogenesis. Antibody against oxLDL (oxLDL Ab) is detectable in human sera, although its biological significance is not well established. We examined the relationship between oxLDL Ab titer and circulating oxLDL level in 130 healthy Japanese subjects. OxLDL was measured as apolipoprotein (apo) B-containing lipoproteins carrying oxidized phosphatidylcholines by a sensitive ELISA. IgG class oxLDL Ab titer was measured by ELISA. Plasma oxLDL concentration was very low and it corresponded on average to one to two out of 1000 apoB-containing lipoproteins in plasma. Plasma oxLDL correlated positively with LDL cholesterol and inversely with oxLDL Ab titer. These associations remained significant and independent in multiple regression analysis including age, gender, smoking, and high-density lipoprotein cholesterol. These data indicate that healthy subjects have a very low concentration of oxLDL in the circulation, and that oxLDL Ab titer is in an inverse relationship with plasma oxLDL concentration in this population. Although these results suggest that oxLDL Ab may play a role in maintaining the low level of plasma oxLDL, its role in atherogenesis awaits further studies.

Adult↗
PubMed2000

Relationship between urinary albumin excretion and glomerular filtration rate in normotensive, nonproteinuric patients with type 2 diabetes mellitus.

BACKGROUND/AIM: In patients with type 2 diabetes mellitus, the relationship between glomerular filtration rate (GFR) and urinary albumin excretion remains an unresolved issue. In order to investigate the early renal function abnormalities, GFR and urinary albumin excretion were assessed, and their relationship was examined in normotensive patients with type 2 diabetes mellitus. METHODS: In a cross-sectional study of 85 nonhypertensive Japanese patients with type 2 diabetes mellitus not showing overt proteinuria, the GFR was measured using (99m)Tc-diethylenetriamine pentaacetate renography. Fifty-one diabetic patients lacked microalbuminuria (albumin excretion <30 mg/day), while 34 patients showed microalbuminuria (between 30 and 300 mg/day). Fifteen healthy subjects served as controls. RESULTS: The three groups were well matched with regard to gender, age, and body mass index. The GFR in microalbuminuric patients (134 +/- 23 ml/min/1.48 m(2)) was significantly higher than in patients without microalbuminuria (108 +/- 21 ml/min/1.48 m(2)) and in controls (109 +/- 18 ml/min/1.48 m(2); p < 0.0001). In type 2 diabetic patients, the GFR positively correlated with the logarithmically transformed urinary albumin excretion. Multiple regression analysis showed that the urinary albumin excretion was significantly and independently affected by GFR (beta = 0.548), duration of diabetes (beta = 0.297), and systolic blood pressure (beta = 0.232; R(2) = 0.409; p < 0.0001). CONCLUSION: It is suggested that one of the mechanisms underlying increased urinary albumin excretion in early nephropathy in normotensive type 2 diabetes is glomerular hyperfiltration.

Adult↗
PubMed2000

Diabetes mellitus worsens intrarenal hemodynamic abnormalities in nondialyzed patients with chronic renal failure.

Duplex Doppler sonography has been reported to be useful in examining the intrarenal hemodynamic abnormalities in various renal diseases. We investigated the impact of diabetes on intrarenal hemodynamics in patients with chronic renal failure (CRF). The resistive index and pulsatility index of the renal interlobar arteries were measured using duplex Doppler sonography in 90 CRF patients (serum creatinine >130 and <800 mmol/l, mean age 59 +/- 11 years). Forty-eight patients had type 2 diabetes and 42 did not. Twenty-nine age-matched, healthy subjects served as controls. Both resistive index and pulsatility index were greater in CRF patients than in the controls (p < 0.0001). No significant differences existed in age, sex, body mass index, total serum cholesterol, serum creatinine, estimated creatinine clearance, or mean blood pressure between the diabetic CRF and nondiabetic CRF groups. Resistive index and pulsatility index were significantly increased in the diabetic CRF patients compared to the nondiabetic CRF patients (p < 0.0001). Multiple regression analysis of all CRF patients revealed that resistive index was independently affected by the presence of type 2 diabetes (F = 44.535), as well as decreased creatinine clearance (F = 18.157) and age (F = 15.160) (R(2) = 0.559, p < 0.0001). These results clearly demonstrated that intrarenal arterial resistance is significantly increased in CRF patients with type 2 diabetes compared to similar patients without diabetes. The impact of diabetes mellitus and advanced age on intrarenal hemodynamics may be due to intrarenal arteriosclerosis and interstitital lesions. Measurements of RI values in addition to conventional ultrasound imaging may add further information on such renal lesions.

Aging↗
PubMed2000

Antibodies against oxidized LDL and carotid artery intima-media thickness in a healthy population.

Oxidation of LDLs plays an important role in atherosclerosis, and immune response to oxidized LDL (oxLDL) may modulate atherogenesis. Although immunization with oxLDL is shown to suppress atherogenesis in animal models, the role of the immune response to oxLDL is not well established in humans. We investigated the relationship between the titer of anti-oxLDL antibody (oxLDL Ab) and arterial wall thickness in a healthy population with no clinical signs of atherosclerosis. Intima-media thickness of the carotid arteries (CA-IMT) was measured by high-resolution B-mode ultrasonography in 446 healthy subjects. The titer of IgG-class oxLDL Ab was measured by a solid-phase ELISA. In univariate analysis, CA-IMT correlated positively with age, systolic blood pressure, total cholesterol, triglyceride, LDL cholesterol, body mass index, and waist-to-hip ratio, whereas it correlated negatively with HDL cholesterol and oxLDL Ab titer. The inverse association between oxLDL Ab titer and CA-IMT remained significant in multiple regression analysis, which took other confounding variables into account. These results indicate an independent inverse relationship between oxLDL Ab titer and CA-IMT in healthy subjects, supporting the hypothesis that immune response to oxLDL may have a protective role at an early stage of human atherosclerosis.

Adolescent↗
PubMed1999

The grading of lymphovascular space invasion in endometrial carcinoma.

BACKGROUND: This study was conducted to elucidate the prognostic significance of a three-grade system for lymphovascular space invasion (LVSI). METHODS: The prognostic significance of the grading of LVSI as compared with other pathologic variables was evaluated in a study of 303 Japanese women with endometrial carcinoma. The criteria for determining the grade of LVSI were as follows: none (no LVSI), mild (a focus of LVSI was recognized around a tumor), and severe (diffuse or multifocal LVSI were recognized around the tumor or in the myometrium regardless of the degree of myometrial invasion). Both univariate and multivariate regression analyses were performed. The effects of different surgical methods and adjuvant therapies on survival were also examined. RESULTS: A univariate survival analysis showed that survival significantly correlated with surgical stage, histologic grade, depth of myometrial invasion, LVSI, cervical invasion, ovarian metastasis, and tubal metastasis. Of the three grades of LVSI, survival showed the most difference between the mild and severe groups. In multivariate analysis, the highest correlation with survival was observed for LVSI (P = 0.0008). Lymph node metastasis was also significantly associated with LVSI (P = 0. 0001). The correlation between histologic variables and survival was only slightly influenced by the differences in surgical methods and adjuvant therapies. CONCLUSIONS: The grading of LVSI was found to be an important histologic prognostic variable. The severe degree of LVSI also was found to be a good indicator of lymph node metastasis. It is therefore important to evaluate the grade of LVSI based on a histologic examination of at least one cut surface of the hysterectomy specimen that macroscopically shows the deepest myometrial invasion.

Endometrial Neoplasms↗