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Biomedical subjects

T Miyata

Publications and source records attributed to T Miyata.

At least 73 records · Page 4Linked to original sources
PubMed2001

High plasma homocyst(e)ine levels in elderly Japanese patients are associated with increased cardiovascular disease risk independently from markers of coagulation activation and endothelial cell damage.

Elevated plasma homocyst(e)ine is a risk factor for cardiovascular disease (CVD) in many populations, but the relationship between homocyst(e)ine and CVD in Japanese subjects has been unclear. It has been hypothesized that the link between homocyst(e)ine and CVD may be mediated in part by activation of coagulation and endothelial cell injury in the elderly Japanese subjects. To further evaluate this hypothesis, the present cross-sectional study was designed to assess the relationships among plasma homocyst(e)ine concentrations, risk of CVD, and markers of coagulation (fibrinogen, FVII, F1+2, FVIIa and FXIIa) and endothelial cell damage (vWF and thrombomodulin) in 146 elderly Japanese subjects (79 healthy controls and 67 patients with CVD). The geometric mean (range) of plasma homocyst(e)ine concentrations was 10.2 (3.2--33) micromol/l in 79 Japanese healthy elderly subjects. As expected, healthy female and male elderly subjects had homocyst(e)ine levels that were 2.5 and 5.3 micromol/; higher, respectively, compared to healthy young control subjects (n=62). Healthy young and elderly men had homocyst(e)ine levels that were 1.7 and 4.5 micromol/l higher, respectively, compared to values in women. This higher plasma homocyst(e)ine levels in the elderly subjects were negatively correlated with levels of folic acid, albumin and total cholesterol, but were not significantly related to markers of coagulation or endothelial cell-damage. The results of multiple logistic regression analyses suggested that high homocyst(e)ine levels were independently related to CVD risk. In addition, levels of FVIIa, and F1+2 were significantly higher in elderly Japanese patients with CVD compared to elderly subjects without CVD, but were unrelated to plasma homocyst(e)ine concentrations. In summary, elevated plasma concentrations of homocyst(e)ine, FVIIa, and F1+2 were associated with increased risk of CVD in elderly male and female Japanese subjects, but the association between homocyst(e)ine and CVD was unrelated to abnormalities in markers of coagulation and endothelial cell damage in this population.

Aged↗
PubMed2001

Silent cerebral infarcts in basal ganglia are advanced in congenital protein C-deficient heterozygotes with hypertension.

Congenital protein C deficiency is now widely recognized as a genetic risk for venous thrombosis. However, it remains uncertain whether this condition also confers risk for arterial thrombosis. We evaluated the association of congenital protein C deficiency with hypertension and silent cerebrovascular disease using brain magnetic resonance imaging (MRI) (T1- and T2-weighted and proton density images) in a large family pedigree of protein C deficiency diagnosed by gene analysis, compared with 46 non-pedigree related control subjects with normal protein C levels (> or = 75%) who were selected from among 55 asymptomatic hypertensive subjects matched for age and cardiovascular risk factors. Of the 58 living subjects in this pedigree, we measured plasma protein C levels in 45 subjects, and found 2 cerebral infarctions in the 24 heterozygotic subjects, whereas there was no stroke in the 21 normal homozygotic subjects. We performed brain MRI in 14 asymptomatic hypertensive subjects without any cardiovascular disease and in two patients with cerebral infarction, and found 28 cerebral infarcts (two corresponded to the patients' neurologic deficits and 26 were silent). All were lacunar infarcts < 10 cm in size. A total of 25 silent lacunar infarcts were found in nine heterozygotic subjects, whereas only one was found in the seven normal homozygotic subjects (2.8 v 0.14 lacunes per person, P = .002). No advanced white matter hyperintense lesions in T2-weighted images were found in either group. The prevalence of silent lacunar infarcts in the heterozygotic subjects was also significantly higher than that in normal control subjects (1.0 per person, P = .01). Concerning the distribution of silent infarcts, the number of lacunes located in the basal ganglia was higher in the heterozygotic subjects (2.3 per person, P < .001) than in the seven normal homozygotic subjects (0.14 per person) or in the control group (0.28 per person), whereas the number of lacunes in the white matter was not different among the groups. In conclusion, congenital protein C deficiency may accelerate the progression of silent cerebral infarct formation in hypertension, particularly in the basal ganglia, and may be a potential risk for stroke or vascularly induced dementia.

Aged↗
PubMed2001

Solubilization study of local anesthetics into sodium dodecyl sulfate micelle using anesthetic cation selective electrodes.

The free concentrations of local anesthetic cations in equilibrium with sodium dodecyl sulfate (SDS) micelle which solubilized the anesthetic were determined by using ion-selective electrodes sensitive to local anesthetics, procaine (PC), lidocaine (LC), and mepivacaine (MC). Solubilizate distribution between water and SDS micelle was analyzed by means of the stepwise mass-action model. Association constant, K(1), was found to depend upon the anesthetic concentration, which decreased exponentially as the concentration of free anesthetic increased. Therefore, K(1) should include the interaction function &phi;(A) as K(1)=K(int)exp{-&phi;(A)} where K(int) is an intrinsic association constant. &phi;(A) is an increasing function of the anesthetic concentration, which means that occupation of a solubilization site by a local anesthetic cation makes sequential solubilization more difficult. The binding affinity of an anesthetic with SDS micelle increased in the following order PC<LC<MC.The critical micelle concentration (CMC) of mixed micelle was determined as a function of the concentration of free anesthetic. The CMC decreased with an increasing amount of anesthetics solubilized. All the anesthetic compositions in the micelle calculated thermodynamically from the CMC data were larger than the corresponding ones in the aqueous phase. Although the local anesthetics used here do not form micelles by themselves, the CMC vs composition curve can be regarded as a part of a micellar phase diagram showing the negative azeotropic behavior, which reflects the attractive interaction between the anionic surfactant micelle and the local anesthetic cation.

Journal Article↗
PubMed2001

Surgical treatment for popliteal artery entrapment syndrome.

PURPOSE: This study was a retrospective review of 11 limbs of 10 patients with popliteal artery entrapment syndrome (PAES) treated surgically in a 20-yr period. METHODS: The patients were aged 34.7 +/- 17.4 SEM yr. Arteriographic findings varied, showing medial deviation in two limbs, poststenotic dilatation in four limbs and occlusion of the popliteal artery in five limbs. In addition, computed tomographic (CT) scanning showed positive findings of PAES in all the limbs. RESULTS: The surgical procedures consisted of musculotendonous section (MTS) with autogenous saphenous vein (ASV) graft in seven limbs, MTS and ASV patch angioplasty with or without thromboendarterectomy in three limbs, and MTS alone in one limb. All the ASV grafts were found to be patent during the postoperative follow-up period (10.9 +/- 4.0 yr). CONCLUSION: CT scanning was demonstrated to be the most sensitive diagnostic modality for PAES, and MTS with or without ASV grafting method was considered to be the best surgical procedure for PAES.

Adolescent↗
PubMed2001

Novel immunotherapy for peritoneal dissemination of murine colon cancer with macrophage inflammatory protein-1beta mediated by a tumor-specific vector, HVJ cationic liposomes.

A critical issue for cancer treatment is control of metastatic or disseminated tumors. Although immune gene therapy has been considered as a possible strategy for treatment of such tumors, successful results have not yet been obtained. To evoke antitumor immunity more efficiently, macrophage inflammatory protein-1beta (MIP-1beta) was used for gene therapy of colon cancer in mice. Injection of hemagglutinating virus of Japan (HVJ) cationic liposomes-MIP-1beta into subcutaneous tumor masses resulted in local expression of MIP-1beta and local accumulation of CD4(+) T lymphocytes. Few studies of cancer gene therapies have targeted peritoneal dissemination. In a mouse model of peritoneal dissemination of colon tumor, we used a luciferase-based assay to demonstrate that HVJ cationic liposomes had high tumor specificity and were effective vectors for transfer of genes in peritoneal dissemination. When mice were treated by intraperitoneal injection of HVJ cationic liposomes containing the MIP-1beta gene, the survival periods of the MIP-1beta-treated mice were significantly longer than those of control mice. Therefore, this HVJ cationic liposome strategy may serve as a powerful tool against peritoneal disseminated cancer.

Animals↗
PubMed2001

Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor promotes collateral development in a rabbit model of hind limb ischemia.

Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor (bFGF), a new strategy for the treatment of chronic vascular occlusive disease, was examined in a rabbit model of hind limb ischemia. The left femoral artery was completely excised to induce an ischemic state in the hind limb of male rabbits. Simultaneously, a skin section was resected from the wound, and host fibroblasts were cultured. The cultured fibroblasts were infected with adenovirus vector containing modified human bFGF cDNA with the secretory signal sequence (AxCAMAssbFGF) or LacZ cDNA (AxCALacZ). At 21 days after femoral artery excision, the gene-transduced fibroblasts were administered through the left internal iliac artery. The fibroblasts significantly accumulated in the ischemic hind limb, and the AxCAMAssbFGF-treated cells secreted bFGF for less than 14 days without elevation of systemic bFGF level. At 28 days after cell administration, calf blood pressure ratio, angiographic score, capillary density of muscle tissue and blood flow of the left internal iliac artery were determined, and animals with AxCAMAssbFGF-treated cells showed significantly greater development of collateral vessels, as compared with those with AxCALacZ-treated cells. These findings suggest that adenovirus-mediated ex vivo gene transfer of bFGF was effective for improvement of chronic limb ischemia.

Adenoviridae↗
PubMed2001

Epinephrine irrigation for the prevention of pancreatic damage after endoscopic balloon sphincteroplasty.

BACKGROUND AND AIM: Endoscopic balloon sphincteroplasty (EBS) is an alternative to sphincterotomy for the treatment of bile duct stones. The purpose of this study was to determine if epinephrine irrigation of the papilla can prevent the pancreatic damage associated with EBS. METHODS: A total of 173 patients with bile duct stones were treated by EBS. After conventional endoscopic retrograde cholangiography, EBS was performed by using a biliary dilatation catheter (balloon diameter: 8 mm). The duct was then cleared by using Dormia baskets or retrieval balloon catheters. Mechanical lithotripsy was performed before extraction when the stones were greater than 8 mm in diameter. In 81 patients, the dilated orifice was irrigated with 40-120 mL (50 +/- 37 mL) of 1:1,000,000 epinephrine (epinephrine group). In the remaining 92 patients, epinephrine irrigation was not performed (control group). Acute pancreatitis was defined by a serum amylase concentration fivefold greater than the upper limits of normal in association with abdominal pain. RESULTS: After EBS, serum amylase concentrations were significantly increased in both groups. However, the degree of hyperamylasemia was less in the epinephrine group than in the control group (617 +/- 611 vs 1037 +/- 1491 IU/L, P < 0.05). The incidence of pancreatitis was lower in the epinephrine group than in the control group (1.2 vs 7.6%, P < 0.05). CONCLUSIONS: Epinephrine irrigation is a simple and useful method to prevent post-EBS pancreatic damage and pancreatitis.

Adult↗
PubMed2001

Glyoxalase I deficiency is associated with an unusual level of advanced glycation end products in a hemodialysis patient.

BACKGROUND: Advanced glycation of proteins and their attendant advanced glycation end products (AGEs) contribute to the complications associated with diabetes mellitus or uremia. Regulatory mechanisms of AGE formation in vivo remain an issue of particular interest. We investigated a role of the glyoxalase detoxification system of precursor reactive carbonyl compounds (RCOs) in the in vivo AGE formation. METHODS: Plasma levels of AGEs [pentosidine and Nepsilon-carboxymethyllysine (CML)], their RCO precursors, d-lactate (the final product resulting from the glyoxalase detoxification pathway), as well as of various compounds known to generate AGE precursors and surrogate markers for oxidative stress (antioxidant enzymes and glutathione), were measured in both hemodialysis (HD) patients and normal subjects. The activity and protein expression of glyoxalase I, an enzyme essential for the detoxification of alpha-oxoaldehydes, in red blood cells (RBC) were also examined. RESULTS: In one 69-year-old lady who had been on hemodialysis (HD) for three years and had suffered from recurrent cardiovascular complications despite the absence of significant risk factors, plasma levels of pentosidine (77.3 +/- 2.4 pmol/mg protein) and CML (330.8 +/- 8.2 pmol/mg protein) were markedly elevated as compared to other HD patients (N = 20: 26.6 +/- 11.8 pmol/mg protein for pentosidine and 224.4 +/- 51.7 pmol/mg protein for CML). The plasma level of RCO precursors for pentosidine and CML was also higher in this patient than in other HD patients. Further investigation disclosed a very low activity in RBC of glyoxalase I (1.5 +/- 0.4 mU/106 RBC), as compared to other HD patients (3.9 +/- 0.6 mU/106 RBC) or normal subjects (4.0 +/- 0.6 mU/106 RBC). The glyoxalase I protein level, assessed in RBC by immunoblot analysis with a specific antibody, was markedly lower than that observed in HD patients and normal subjects. The causes of this deficiency remain unknown. Nucleotide sequencing of the products of reverse transcription-polymerase chain reaction from the patient's mononuclear cells revealed no genetic mutation within the coding region of the glyoxalase I gene. Plasma d-lactate level was also in the lower range (0.18 +/- 0.03 mg/dL) of the values measured in the other HD patients (0.27 +/- 0.09 mg/dL) and normal subjects (0.35 +/- 0.12 mg/dL). The plasma levels of various compounds known to generate AGE precursors (glucose, lipids and ascorbic acid) were either normal or low. The surrogate markers for oxidative stress such as antioxidant enzymes (glutathione peroxidases and superoxide dismutase) and glutathione were all within the range observed in the other HD patients. CONCLUSION: The unusually high levels of AGEs in this patient implicate a deficient glyoxalase detoxification of RCO precursors. The present clinical observation implicates, to our knowledge for the first time, the glyoxalase detoxification system and, in particular, glyoxalase in the actual level of AGEs in a uremic patient.

Aged↗
PubMed2001

Clusterin is up-regulated in glomerular mesangial cells in complement-mediated injury.

BACKGROUND: Clusterin is a soluble complement regulatory protein that binds to C5b-7 and inhibits generation of membrane attack complex, C5b-9. Glomerular deposition of clusterin has been observed in human and experimental membranous nephropathy in association with C5b-9 and immune deposits. However, it is controversial as to whether clusterin observed in glomeruli is synthesized by the resident glomerular cells or is derived from the circulation. We examined whether clusterin is expressed by resident glomerular cells exposed to complement-mediated injury. METHODS: In vitro, cultured mesangial cells were exposed to antithymocyte serum immunoglobulin G and 5% normal rat serum as a complement source. In vivo, we induced anti-Thy1 nephritis in rats and examined the kidneys on days 8 and 29. RESULTS: We observed increased expression of clusterin in cultured rat glomerular mesangial cells stimulated by sublytic complement attack. We also demonstrated that in comparison with control rats, both a marked increase in clusterin mRNA in the glomeruli and marked deposition of clusterin protein in the mesangial area occurred in the OX-7-treated rats on day 8 in association with C5b-9 deposition and on day 29. CONCLUSION: Clusterin was induced in glomerular mesangial cells during the course of immune-mediated injuries. This up-regulation of clusterin may play a critical role in protecting mesangial cells from complement attack.

Animals↗
PubMed2001

Cytoprotective role of heme oxygenase (HO)-1 in human kidney with various renal diseases.

BACKGROUND: We previously reported that glomerular changes in the renal specimen of a human case with heme oxygenase-1 (HO-1) deficiency were mild, but tubulointerstitial injury advanced progressively. This study examined the patterns of HO-1 production in the kidney in various renal diseases. Furthermore, the critical cytoprotective roles of HO-1 were evaluated in the kidney by comparing HO-1 production and expressions of carboxymethyllysine (CML) and pentosidine, both of which are markers of oxidative stress. METHODS: Renal biopsy or autopsy materials were obtained from a total of 74 patients. Degrees of hematuria and proteinuria and the levels of urinary N-acetyl-beta-D-glucosaminidase (NAG), beta2-microglobulin (beta2m), and creatinine were evaluated. Immunohistochemical studies for HO-1, CML, and pentosidine expressions were performed with their specific antiserum. RESULTS: HO-1 staining was observed within tubular epithelial cells in all of the renal diseases, but was not detected within intrinsic glomerular cells. HO-1 staining tended to be more intense within distal tubuli than in proximal tubuli. Within distal tubuli, there was no significant correlation between intensity of HO-1 staining and degree of hematuria or presence of proteinuria. Within proximal tubuli, HO-1 staining tended to be more intense with greater degrees of hematuria, presence of proteinuria, and moderate tubulointerstitial damage. Intense staining of CML and pentosidine was observed within renal tubular epithelial cells only in HO-1-deficient patients. CONCLUSIONS: HO-1 plays important roles in protecting renal tubuli from oxidative injuries, as these cells are constantly exposed to various oxidative stresses. It is suggested that renal tubular epithelia are more susceptible to oxidative stress due to the lack of this critical enzyme in HO-1 deficiency.

Adolescent↗
PubMed2001

beta(2)-Microglobulin modified with advanced glycation end products delays monocyte apoptosis.

BACKGROUND: A local inflammatory reaction to beta(2)-microglobulin (beta(2)m) amyloid deposits by monocytes/macrophages is a characteristic histologic feature of dialysis-related amyloidosis (DRA). Since beta(2)m modified with advanced glycation end products (AGE-beta(2)m) is a major constituent of amyloid in DRA, we tested the hypothesis that AGE-beta(2)m affects apoptosis and phenotype of human monocytes. METHODS: Human peripheral blood monocytes were incubated with or without in vitro-derived AGE-beta(2)m, and their viability, extent of apoptosis, morphology, and function examined over the subsequent four days. RESULTS: AGE-modified but not unmodified beta(2)m significantly delayed spontaneous apoptosis of human peripheral blood monocytes in adherent and nonadherent cultures. The effect of AGE-beta(2)m on monocytes apoptosis was time- and dose-dependent and was attenuated by a blocking antibody directed against the human AGE receptor (RAGE). There was no difference in effect between AGE-beta(2)m and that of AGE-modified human serum albumin. Culture of monocytes with AGE-beta(2)m did not alter membrane expression of Fas or Fas ligand. Monocytes cultured with AGE-beta(2)m underwent substantial changes in morphology similar to those observed when monocytes differentiate into macrophages. The cultured cells increased in size and vacuolization, and their content of beta-glucuronidase and acid phosphatase increased by 5- to 10-fold at day 4. Expression of the monocyte--macrophage membrane antigens HLA-DR, CD11b, and CD11c also increased at day 4. Although exhibiting phenotypic characteristics of macrophages, monocytes cultured with AGE-beta(2)m functioned differently than macrophages cultured with serum. Superoxide production in response to phorbol myristic acetate was maintained in monocytes cultured with AGE-beta(2)m, but declined with time in cells cultured with serum. Constitutive synthesis of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2) increased in monocytes cultured for four to six days with AGE-beta(2)m. CONCLUSIONS: These findings support a novel role for AGE-modified proteins such as AGE-beta(2)m that may contribute to the development of a local inflammatory response, with predominant accumulation of monocytes/macrophages, in DRA.

Antibodies↗
PubMed2001

Cloning of rodent megsin revealed its up-regulation in mesangioproliferative nephritis.

BACKGROUND: We recently cloned a new human mesangium-predominant gene, megsin. Megsin is a novel member of the serine protease inhibitor (serpin) superfamily. To elucidate functional roles of this gene, we cloned megsin in rodents and investigated its role in a rat nephritis model. METHODS: Megsin homologues were cloned from cultured rat and mouse mesangial cDNAs utilizing polymerase chain reaction (PCR) with degenerative primers. Expression of megsin in three different types of resident glomerular cells was investigated by PCR. Levels of megsin mRNA expression at various time points in the anti-Thy1 rat nephritis model were studied by semiquantitative PCR and Northern blotting analysis. In order to investigate megsin protein expression in anti-Thy1 nephritis rats, we raised antibody against rat megsin-specific synthetic peptide, with which immunohistochemical studies were performed. RESULTS: Rat and mouse megsins were composed of 380 amino acids, which revealed 75.3 and 73.9% identity, respectively, with human megsin at the amino acid level. Characteristic features as an inhibitory serpin were conserved in both rat and megsin megsins. PCR analysis revealed expression of megsin in cultured mesangial cells but not in glomerular epithelial or endothelial cells. In anti-Thy1 nephritis rats, semiquantitative PCR and Northern blotting showed that expression of megsin mRNA was up-regulated in glomeruli at day 8. Immunohistochemical studies demonstrated the prominent accumulation of megsin in glomeruli at the same time point. Megsin was mainly localized in mesangial area. The megsin expression level returned to the basal level at day 28. CONCLUSION: Sequences of megsin were well conserved among different species. Rat megsin was also predominantly expressed in mesangial cells. Expression of megsin was up-regulated at the peak of hypercellularity and matrix accumulation in the mesangioproliferative glomerulonephritis model, suggesting that megsin may participate in the process of glomerulosclerosis by modulating extracellular matrix deposition or cell survival.

Amino Acid Sequence↗
PubMed2001

Reactive carbonyl compounds related uremic toxicity ("carbonyl stress").

Many studies on uremic toxins have focused on enzymatic biochemistry. Recently, attention has turned to nonenzymatic biochemistry, especially progressive and irreversible modifications of proteins. Two different approaches opened the field of irreversible nonenzymatic modifications of proteins in uremia: the advanced glycation end products (AGEs) derived from the Maillard reaction and the advanced lipoxidation end products (ALEs) derived from lipid peroxidation. They have revealed the accumulation of reactive carbonyl compounds (RCOs) derived from carbohydrates and lipids and the subsequent carbonyl modifications of proteins ("carbonyl stress"). In this article, we describe the causal role of various RCOs and AGEs/ALEs accumulating in uremia, the clinical consequences of carbonyl stress in uremia, and finally, the therapeutic perspectives. We propose carbonyl stress as a new uremic toxicity.

Amyloidosis↗
PubMed2001

A honeycomb collagen carrier for cell culture as a tissue engineering scaffold.

As a three-dimensional carrier for cell culture, a honeycomb structure cell scaffold was created from atelopeptide collagen Types I, II, and III. The diameter of the honeycomb pores ranged from 100 to 1,000 microm. The depth of the pores was from 10 to 3,000 mm. The scaffold was elastic and hard. Creation of various shapes was easy, and these shapes were easily maintained. Human fibroblasts, CHO-K1, BHK-21, and bovine endothelial cells were cultured with the scaffold. The growth curves of these cells were satisfactory. These results suggest that this carrier is a suitable scaffold for cell culture and will be useful as a three-dimensional tissue engineering scaffold.

Animals↗
PubMed2001

Total enteroscopy with a nonsurgical steerable double-balloon method.

BACKGROUND: Deep insertion of an enteroscope by use of a push technique is difficult. A new method of enteroscopy was developed, a double-balloon method, to improve the access to the small intestine. METHODS: The new method uses 2 balloons, one attached to the tip of the endoscope and another at the distal end of an overtube. By using these balloons to grip the intestinal wall, the endoscope can be inserted further without forming redundant loops in the small intestine. This method was tried with a standard upper endoscope in 3 patients and with a longer enteroscope in 1 patient. RESULTS: Despite its short length the upper endoscope was successfully inserted as far as 30 to 50 cm beyond the ligament of Treitz in the 3 patients. In the fourth patient the longer enteroscope was successfully inserted beyond the ileo-cecal valve. CONCLUSIONS: The double-balloon method facilitates endoscopic access to the small intestine.

Adolescent↗
PubMed2001

Successful management of tracheo-innominate artery fistula with endovascular stent graft repair.

Tracheo-innominate artery fistula is a highly lethal complication after tracheostomy. A 37-year-old man who had undergone a tracheostomy 14 years earlier because of dysphagia after brain surgery had a tracheo-innominate artery fistula with exsanguinating hemorrhage from his tracheostomy site. After temporary control of the bleeding, a stent graft was implanted in the innominate artery through the brachial artery. The patient recovered uneventfully and remained well 14 months after the procedure, with no sign of infection. Endovascular stent grafting may be the treatment of choice for patients with tracheo-innominate artery fistula.

Adult↗
PubMed2001

Extracranial carotid aneurysm in Takayasu's arteritis.

Extracranial carotid aneurysm caused by Takayasu's arteritis is extremely rare. We have experienced six cases of extracranial carotid aneurysm among 106 cases of Takayasu's arteritis that were treated surgically in the past 50 years. We herein review these cases and discuss the surgical indications and postoperative course of this rare disease. We report original observations about extracranial carotid aneurysm in Takayasu's arteritis.

Adult↗