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Biomedical subjects

Y Motomiya

Publications and source records attributed to Y Motomiya.

At least 19 recordsLinked to original sources

A possible role for leptin in normo- or hypoparathyroid uremic bone in postmenopausal dialysis women.

Leptin has been proposed to be a key molecule involved in energy regulation. Based on the generally acknowledged concept that a heavier person has a higher bone density, leptin is thought to be potentially involved in bone metabolism. Serum leptin, various bone markers, and bone mineral density (BMD) were studied in 51 dialysis patients (26 men and 25 women). The serum concentrations of leptin in dialysis patients ranged from 0.7 to 10.4 ng/ml (mean 3.2 +/- 2.1 ng/ml) for males and from 1.4 to 44.6 ng/ml (mean 11.8 +/- 10.4 ng/ml) for females. There was a good correlation between the body mass index (BMI) and leptin concentration in both male and female patients (P < 0.05). Serum leptin levels also correlated well with the age-adjusted z-score for BMD (P < 0.02) and were inversely correlated with levels of the carboxy-terminal propeptide of type I procollagen (P < 0.05) in females patients, but not in male patients. In conclusion, these results suggest an actual contribution of serum leptin in maintaining bone density in postmenopausal female dialysis patients.

Adult↗

Potential value of CML-Hb in predicting the progression of bone cysts in dialysis-related amyloidosis.

BACKGROUND/AIM: Carboxymethyllysine is one of the common advanced glycation end products in vivo. In a previous report, we were the first to describe the increase of circulating carboxymethyllysine-hemoglobin (CML-Hb) levels in hemodialysis patients, particularly in patients with dialysis-related amyloidosis (DRA). The aim of this study was to investigate the predictive value of CML-Hb in the progression of DRA using computed tomography images of 2-year or 3-year follow-up periods of patients with amyloid bone cysts at the hip joint. METHODS: Circulating CML-Hb levels were measured as previously reported, and computed tomography scanning was conducted from 1996 to 1998 or 1999 in 57 hemodialysis patients whose original renal disease had been confirmed to be nondiabetic. Patients who showed a new growth of cysts or a growth rate of 30% or more were classified as progressive cases, while the other patients were classified as nonprogressive cases. RESULTS: (1) The circulating CML-Hb levels showed a strong correlation with the DRA score by multiple regression analysis, and (2) patients with progression of amyloid cysts showed a significantly higher circulating CML-Hb level than patients without progression. CONCLUSION: Based upon these results, we conclude that measurement of circulating CML-Hb levels has a potential value in both judgment of the clinical state and prediction of progression of DRA in hemodialysis patients.

Amyloidosis↗

Elevation of N-(carboxymethyl)valine residue in hemoglobin of diabetic patients. Its role in the development of diabetic nephropathy.

OBJECTIVE: Advanced glycation end products (AGEs) are a risk factor for diabetic complications. We have developed an assay method for N-(carboxymethyl)valine (CMV) of the hemoglobin (CMV-Hb), which is an AGE generated from HbA1c. Herein we describe the clinical utility of CMV-Hb measurement for the diagnosis of diabetic nephropathy RESEARCH DESIGN AND METHODS: BALB/c mice were immunized with carboxy-methylated Hb and monoclonal antibody raised against CMV-Hb. This antibody was characterized by a surface plasmon resonance. We developed a latex immunoassay using the antibody and measured CMV-Hb from erythrocytes in type 2 diabetic patients and healthy control subjects (age 64.6 +/- 12.0 vs. 61.1 +/- 13.2 years, NS: HbA1c 69 +/- 1.5 vs. 5.2 +/- 0.4%, P < 0.0001). RESULTS: A monoclonal antibody against CMV-Hb beta-chain NH2-terminal and an assay method for measurement for CNMV-Hb were both developed in our laboratory. CMV-Hb levels were significantly greater in the diabetic patients than in the control subjects (18.2 +/- 6.9 vs. 12.7 +/- 0.9 pmol CMV/mg Hb, P < 0.0001). No correlation was found between CMV-Hb and HbA1c or CMV-Hb and glycated albumin. Levels of CMV-Hb increased as the diabetic nephropathy progressed. CONCLUSIONS: We established an assay method for CMV-Hb and confirmed the presence of CMV-Hb in circulating erythrocytes. CMV-Hb was more prevalent in diabetic patients than in healthy subjects. Furthermore, it was significantly higher in patients with diabetic nephropathy, suggesting that the presence of CMV-Hb may be a valuable marker for the progression of diabetic nephropathy.

Animals↗

Immunochemical assay of hemoglobin with N(epsilon)-(carboxymethyl)lysine at lysine 66 of the beta chain.

BACKGROUND: N(epsilon)-(Carboxymethyl)lysine (CML), a well-characterized and major advanced glycation end product structure, is produced via a Maillard reaction by nonenzymatic glycation and/or oxidation. Although few of the carboxymethylation sites of lysine residues on proteins have been identified, it is known that the possible lysine glycation site in hemoglobin (Hb) is Lys-66 on the beta chain. We aimed to develop an assay for the Hb with a CML (CML-Hb) site specific to Lys-66 on the Hb beta chain and to determine whether the lysine residue at that site is carboxymethylated. METHODS: Ala-His-Gly-Lys-Lys(CM)-Val-Leu-Gly-Ala-Phe-Ser-Cys, the peptide derived from the beta chain of human Hb, was synthesized as an immunogen, and a monoclonal antibody against the peptide was prepared. A latex immunoassay method was established using the antibody on an automatic analyzer. In this study, 20 samples from healthy subjects and 80 samples from nondiabetic patients undergoing hemodialysis (HD) were analyzed. RESULTS: The latex immunoassay method using the antibody correlated significantly with the ELISA method using the antibody (r = 0.95; P <0.001). Between healthy subjects (n = 20) and nondiabetic HD patients (n = 80), a significant difference was seen in circulating CML-Hb (525 +/- 76 vs 778 +/- 137 pmol CML/mg of Hb; P <0.0001). CONCLUSION: The latex method for the CML-Hb site specific to Lys-66 on the beta chain can measure large numbers of samples on an automatic analyzer.

Acetaldehyde↗

Usefulness of long axis M-mode echocardiographic measurements for optimum dialysis in patients on maintenance hemodialysis: comparison with changes in plasma levels of atrial natriuretic peptide and brain natriuretic peptide.

UNLABELLED: It has been suggested that analyzing the left ventricular long axis motion can result in the sensitive detection of cardiac functional disorders. AIM: To evaluate the usefulness of left ventricular long axis indices in managing patients on maintenance hemodialysis. METHODS: Eighteen hemodialysis patients (mean age 51 +/- 10 years) as well as 16 healthy persons (mean age 49 +/- 9 years) were examined. Echocardiograms were recorded, and the plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured before and after a session of hemodialysis. The following parameters were measured: the left atrial diameter (LAD) and end-diastolic left ventricular diameter (LVDd) from M-mode echocardiograms, the end-diastolic LV volume (LVEDV) and ejection fraction (EF) from 2-D echocardiography, the E/A ratio from transmitral Doppler, the atrial systolic excursion of long axis motion of the mitral ring (ALAM) and maximal lengthening rate of the mitral ring toward the left atrium during the early diastolic phase (MLRe) from LV long axis M-mode echocardiograms. RESULTS: LAD, LVDd, LVEDV, and ALAM showed a positive correlation with plasma levels of ANP and BNP. EF, the E/A ratio, and MLRe showed a negative correlation with plasma levels of ANP and BNP. Changes in ALAM and plasma levels of ANP during hemodialysis were larger in the subgroup of ALAM < or = 0.55 cm before hemodialysis than in the subgroup of ALAM < 0.55 cm before hemodialysis. CONCLUSION: These results indicate that the left ventricular long axis index can detect a disorder of left ventricular diastolic function, and that a hemodialysis patient whose ALAM before hemodialysis is < 0.55 cm is dialyzed with good volume control conditions.

Adult↗

N epsilon-(carboxymethyl)lysine in blood from maintenance hemodialysis patients may contribute to dialysis-related amyloidosis.

BACKGROUND: Recent studies demonstrated not only that advanced glycation end product could be found in amyloid tissue from patient with dialysis related amyloidosis, but also that amyloid beta2-microglobulin was modified with N(epsilon)-(carboxymethyl)lysine (CML). We wanted to determine if CML could be a biomarker in these patients. METHODS: To raise polyclonal anti-carboxymethyllysine antibody, human serum albumin was carboxymethylated by glyoxylic acid and was immunized to rabbits as antigen. Carboxymethyllysine-hemoglobin (CML-Hb) levels were measured by the dot blotting method using this antibody. RESULTS: The levels of CML-Hb were 6.68 +/- 3.10 nmol CML/mg Hb in nondiabetic hemodialysis patients (N = 70), 6.39 +/- 3.43 nmol CML/mg Hb in diabetic hemodialysis patient (N = 21), and 3.13 +/- 0.88 nmol CML/mg Hb in 47 healthy volunteers. For clinical signs of dialysis-related amyloidosis, 70 nondiabetic hemodialysis patients were scored according Gejyo's criteria. The CML-Hb levels in patients with a high amyloid score as well as a low amyloid score were significantly higher than in patients with negative amyloid score (8.89 +/- 3.53 nmol CMLmg Hb, 7.28 +/- 2.32 nmol CML/mg Hb vs. 5.11 +/- 2.09 nmol CML/mg Hb, P < 0.001, P < 0.05). Furthermore, the CML-Hb levels correlated significantly with serum values of the methylguanidine over creatinine ratio and hyaluronate. CONCLUSIONS: We suggest that CML-Hb is increased in blood from patients on maintenance hemodialysis and is thus a potential biomarker of oxidative damage in these patients. Moreover, CML-modification of protein may play a pathogenic role in the development of dialysis related amyloidosis.

Adult↗

IL-6 mRNA synthesis by peripheral blood mononuclear cells (PBMC) in patients with chronic renal failure.

We measured levels of IL-6 mRNA in PBMC obtained from patients with chronic renal failure, using polymerase chain reaction (PCR). PBMC were isolated from 45 patients on haemodialysis (HD) at the start of HD. PBMC were also isolated from 35 patients on HD at the end of HD, 23 patients on continuous ambulatory peritoneal dialysis (CAPD), 24 undialysed patients with chronic renal failure (CRF), and 19 healthy controls. Total RNA was extracted from PBMC with RNA zol and reverse transcribed into cDNA. To prepare samples containing identical amounts of beta-actin cDNA, we performed competitive PCR by co-amplifying serial dilutions of mutant templates containing a single point mutation which generated a unique Eco RI site. Next, to measure IL-6 cDNA semiquantitatively in the samples containing identical amounts of beta-actin (100 pg), we performed PCR amplification using 2 fg of the IL-6 mutant template containing a unique Eco RI site. Higher levels of IL-6 mRNA in the PBMC were observed in the HD patients than in the CAPD patients and healthy controls. The levels of IL-6 mRNA in the PBMC at the end of HD were not significantly higher than those at the start of HD. These results suggest that the dialysis session itself did not significantly affect IL-6 mRNA levels in the PBMC, but that chronic stimulation by maintenance HD may be associated with higher levels of IL-6 mRNA observed in HD patients.

Adult↗

[Plasma allantoin in patients undergoing maintenance hemodialysis].

Recently, it has been noted that radical molecules participate in the pathogenesis of some of the complications associated with long-term dialysis therapy, such as amyloidosis. Since allantoin is produced from uric acid almost exclusively by the hydroxy radical, we investigated the plasma concentrations of allantoin in 71 patients with chronic renal failure who were on maintenance hemodialysis. Our specific objective was to investigate the relation of allantoin to the plasma concentrations of beta2-microglobulin and methylguanidine to evaluate the potential of allantoin as a significant parameter of the radical reaction. Although plasma allantoin was not detected in 15 healthy controls, plasma concentrations of allantoin increased markedly in all of the hemodialysis patients (42.6 +/- 37.7 nmol/mL) and wide variation was observed from 4.3 to 185.2 nmol/mL. In addition, we confirmed significant correlations between plasma concentrations of allantoin and beta2-microglobulin as well as serum concentrations of methylguanidine/creatinine and hyaluronic acid (r - 0.456, p < 0.0005, r = 0.313, p < 0.005, r = 0.368, p < 0.01, respectively). Although evidence for a direct link between plasma allantoin levels and amyloidosis was not obtained, the increase in the plasma concentrations of allantoin suggested its clinical significance as a parameter of the radical reaction that is thought to participate closely in the pathogenesis of dialysis-related amyloidosis. From a practical point of view, the measurement of plasma allantoin can be expected to become a significant method of measuring radical members which may be useful in the prophylaxis of some of the complications induced by free radicals.

Adolescent↗

[Serum and urinary pyridinium cross-links in patients with predialysis chronic renal failure].

The concentrations of pyridinoline (Pyr), a novel marker of bone resorption, were simultaneously measured in both serum and urine samples by ion-paired high-performance liquid chromatography in 27 patients with predialysis chronic renal failure. The patients consisted of 19 males and 8 females, whose creatinine clearance (Ccr) ranged from 2.5 to 47.6 ml/min. The influence of residual renal function on serum Pyr and the clinical significance of serum and urinary Pyr were analyzed in patients with predialysis chronic renal failure. There were significant correlations between serum Pyr and serum Cr (r = 0.76) and between Pyr clearance and Ccr (r = 0.70). In addition, significant correlations were observed serum and urinary Pyr (r = 0.64) and between both serum and urinary Pyr and HS-PTH (r = 0.96 and r = 0.61, respectively) and osteocalcin (r = 0.80 and r = 0.73, respectively). However, serum bone alkaline phosphatase isoenzyme (ALP3) was correlated with neither serum nor urinary Pyr. There was no correlation between the ratio of serum Pyr/serum Cr and the metabolic bone markers (HS-PTH, osteocalcin and ALP3). There was a correlation between Ccr and urinary Pyr, although it was statistically significant (p < 0.1). These date led to the following conclusions: (1) serum Pyr in patients with oredialysis chronic renal failure is influenced by reduced renal function and (2) urinary pyr shows a state of bone resorption when an adegvafe level of renal function is maintained. This suggests that patients with an advanced stage of renal osteodystrophy are included among cases of predialysis chronic renal failure.

Adult↗

[Measurement and clinical significance of serum concentrations of pyridinium cross-links in patients with renal osteodystrophy].

Serum concentration of the pyridinium cross-links, pyridinoline (Pyr) and deoxypyridinoline (Dpyr), which are markers of bone resorption, was measured by high-performance liquid chromatography in 56 patients on maintenance hemodialysis. The following analyses were conducted: 1) correlation with known markers of bone metabolism, 2) correlation with findings on bone changes on plain X-ray film, 3) elimination rates by hemodialysis, and 4) increment per day in pyridinoline after hemodialysis (delta Pyr/day). There was a very close correlation found between serum Pyr and Dpyr (r = 0.861). Both serum Pyr and Dpyr showed correlations with known markers of bone metabolism: C-PTH (r = 0.806 and r = 0.747, respectively), M-PTH (r = 0.766 and r = 0.749), osteocalcin (r = 0.717 and r = 0.693), Alp-3 (r = 0.523 and r = 0.441) and tartrateresistant acid phosphatase (r = 0.549 and r = 0.548). In addition, a correlation between the duration of hemodialysis and serum Pyr and Dpyr was observed (r = 0.426 and r = 0.318, respectively). When comparing the mean values of serum Pyr or Dpyr in three groups of patients divided according to bone changes seen on plain X-ray film, there were statistically significant differences between the group without bone changes and the remaining two groups with some bone changes (p < 0.05). A mean of 45.3% of serum Pyr was removed by hemodialysis. The serum Pyr level returned almost to the original concentration by the following hemodialysis. delta Pyr/day showed a close correlation with C-PTH (r = 0.656).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[A study on markers of bone metabolism in patients with non hypercalciuric calcium stone--measurement of gamma-carboxyglutamic acid and hydroxyproline].

Thirty-one patients (26 male and 5 female patients) of non-hypercalciuric Ca stone formers were studied concerning their bone metabolism. We measured plasma free gamma-carboxyglutamic acid, plasma hydroxyproline, urinary free gamma-carboxyglutamic acid and urinary hydroxyproline as markers of bone metabolism. Plasma free gamma-carboxyglutamic acid level showed significantly higher in stone formers than normal controls (1.01 +/- 0.37 nmol/ml vs 0.39 +/- 0.13 nmol/ml). But no significant difference were observed in plasma hydroxyproline level (1.99 +/- 0.73 micrograms/ml vs 2.27 +/- 0.92 micrograms/ml), urinary free gamma-carboxyglutamic acid (52.0 +/- 17.6 nmol/mg.Cr vs 45.7 +/- 9.8 nmol/mg.Cr), and urinary hydroxyproline (3.87 +/- 2.02 micrograms/mg.Cr vs 3.33 +/- 1.63 micrograms/mg.Cr). In conclusion, these results suggest that abnormality of bone metabolism may be not a primary event in causing stone formation in these patients.

1-Carboxyglutamic Acid↗

Fibroadenoma associated with gynaecomastia in an adult man. Case report.

A 40-year-old man was operated on for gynaecomastia, and on histological examination the enlarged breast tissue was found to contain a fibroadenoma. Fibroadenoma of the breast is extremely rare in men, and this is the first report to our knowledge of a fibroadenoma associated with idiopathic gynaecomastia.

Adult↗

[Lymphocyte subpopulations in maintenance hemodialysis patients receiving recombinant human erythropoietin].

The effect of recombinant human erythropoietin (rHuEPO) on the lymphocyte subpopulations of maintenance hemodialysis patients has been studied. Peripheral lymphocyte counts, lymphocyte subpopulations (Two color analysis) and PHA-induced proliferative response were measured before and after rHuEPO administration during 8 months in 22 stable hemodialysis patients (mean age 52 years, mean duration of dialysis 48 months). We could find a significant increase in the proportions of CD4+ Leu8- cells, HLA-DR+ cells, CD8+ HLA-DR+ cells, CD14+ HLA-DR+ cells and CD4+ Leu8-/CD8+ CD11b+ cells ratios after rHuEPO therapy. In addition, a significant decrease in the proportions of CD16+ CD57- cells and CD20+ cells could be found after rHuEPO therapy. These results suggest that rHuEPO administration to stable hemodialysis patients induces increases in lymphocytes categorized into helper subset groups and in activated T lymphocytes.

Adult↗

[A study on plasma allantoin in patients undergoing maintenance hemodialysis].

Current studies have reported that free radical molecules had anticipated intimately with the pathogenesis of some complications specific for a long term hemodialysis. Among substances generated by free radical reaction, methylguanidine (MG) had been well known as most popular parameter in hemodialyzed patient, but allantoin (Alt) had been reported to be generated from uric acid by hydroxyradical, too. In this study, we measured serum level of Alt in long term hemodialyzed patient and analysed in the comparison with serum level of sialic acid, MG, and MG/Cr value. Serum level of Alt in patients group varied from 2.6 to 105.9 nmol/ml, which was significantly higher as compared with exclusively undetectable level in normal volunteers (n = 15). Serum level of Alt in each patient showed a significant correlation with serum level of a sialic acid (r = 0.400 p < 0.02). Furthermore, although serum level of Alt failed to show a significant correlation with serum level of MG, but showed a significant correlation with MG/Cr value. (r = 0.485 p < 0.01). In addition, higher level could be found in patient group having higher serum level of MG or MG/Cr value. Based upon those results, we proposed that a measurement of serum level of Alt could be of value in detection of free radical reaction in long term hemodialyzed patient.

Adolescent↗

[A study on urinary free gamma-carboxyglutamic acid in patients with idiopathic urinary calcium stone].

Currently, urinary excretion of free gamma-carboxyglutamic acid (gamma-gla.), a terminal amino acid degraded from gamma-gla. containing protein including bone Gla. Estimated to be a more specific marker for bone metabolism and useful clinically rather than urinary excretion of hydroxyproline. In addition, serum levels of BGP have proved to be a significantly valuable indicator for bone metabolism, especially for process of bone formation, in recent studies. Therefore, we measured these parameters in 40 patients with idiopathic urinary calcium (Ca) stone and investigated bone metabolism in those patients. However, in majority of cases studied, urinary levels of gamma-gla. as well as that of hydroxyproline proved to be definite difference from that in healthy subjects (n = 12) and failed to suggest the presence of abnormality in bone turnover in the background of stone formation. Urinary excretion of hydroxyproline were 6.68 +/- 3.89 micrograms/mg.Cr in the patients and 6.95 +/- 3.08 micrograms/mg.Cr in healthy subjects. Urinary excretion of gamma-gla were 55.0 +/- 15.8 nmol/mg.Cr in the patients and 47.2 +/- 7.3 nmol/mg.Cr in healthy subjects.

1-Carboxyglutamic Acid↗

Long-term follow-up of a patient with lateral calcaneal flaps for bilateral posterior heel necrosis.

Lateral calcaneal flaps were used to cover the skin necrosis of bilateral posterior heels, and a favorable result was obtained. During the first 5 years after surgery, the patient enjoyed hiking as before and made favorable progress, having no trouble in the region covered with the flap and attaining sensory cortical reorientation soon after surgery. Paresthesia of donor sites was reduced in its extent and caused no difficulties in everyday life, but it remained after the lapse of 5 years. The medical record of this patient during the 5 years is reviewed, and we discuss the indications of a lateral calcaneal flap.

Burns↗

[Study of tartrate resistant acid phosphatase in patients with chronic renal failure on maintenance hemodialysis].

In the diagnosis of renal osteodystrophy (ROD) and the monitoring of its clinical course, several biochemical parameters have been appreciated as a useful indicators. The present investigations were designed to evaluate the clinical value of serum tartrate resistant acid phosphatase (TRACP) as an additional parameter of osteoclastic activity in ROD based upon the concept that TRACP was marker enzyme specific for osteoclast. Serum TRACP was assayed in 72 patients on long term hemodialysis and compared with conventional parameters of ROD such as ALP, Osteocalcin, Hydroxyproline. Bone change was analyzed according to Jensen's method and categorized into 4 stages. Serum TRACP was exclusively elevated and revealed a evident correlations with each parameters as follows: TRACP v. PTH-C, r = 0.501 p less than 0.01. Hydroxyproline, r = 0.429 p less than 0.05., ALP, r = 0.001., Osteocalcin, r = 0.540 p less than 0.01. In addition, TRACP value in the patients with high stage significantly higher than that in those low stage ROD. These results suggest that measurement of TRACP would be of clinical importance and useful for diagnosis of ROD in chronic maintenance hemodialized patients.

Acid Phosphatase↗