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Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 91 records · Page 5Linked to original sources
PubMed2001

Comparison of lymphocyte depletion and clinical effectiveness on filtration leukocytapheresis in patients with rheumatoid arthritis.

We evaluated the relationship between the clinical benefit of filtration leukocytapheresis (LCP) and the number of removed leukocytes in patients with rheumatoid arthritis (RA). LCP was performed in 31 drug-resistant RA patients. LCP was carried out 3 times with 1 week separating each session. Assessment of RA before and after LCP showed a substantial and rapid improvement in tender joint counts, swollen joint counts, and patients' and physicians' assessments. Careful analysis indicated that 19 of 31 patients with RA showed > or = 20% improvement following LCP therapy. The number of leukocytes in the peripheral blood significantly decreased during each session of LCP. However, there was no significant decrease in the number of circulating blood cells during the study period. No adverse reactions or complications were noted. There was no significant difference in any indices of clinical activity and the removal rates of leukocytes between responders and nonresponders. The total numbers of removed lymphocytes in responders were significantly higher than those in nonresponders (responders 64.1 x 10(8) versus nonresponders 50.7 x10(8), p < 0.05). The relationship between clinical effectiveness and the number of removed granulocytes and monocytes was not statistically significant. Our results suggest that filtration LCP to remove leukocytes from the peripheral blood, especially lymphocytes, exerts an immunomodulatory effect in patients with RA.

Adult↗
PubMed2001

Tonsillectomy and steroid pulse therapy significantly impact on clinical remission in patients with IgA nephropathy.

We conducted a retrospective investigation of renal outcome in 329 patients with immunoglobulin A (IgA) nephropathy with an observation period longer than 36 months (82.3 +/- 38.2 months) in our renal unit between 1977 and 1995. Clinical remission, renal progression, and the impact of covariates were estimated by Kaplan-Meier analysis and a Cox regression model. In 157 of 329 patients (48%), disappearance of urinary abnormalities (clinical remission) was obtained. None of these 157 patients showed progressive deterioration, defined as a 50% increase in serum creatinine (Scr) level from baseline, during the observation period. Conversely, in patients without clinical remission, the Kaplan-Meier estimate of probability of progressive deterioration was 21% +/- 5% at 10 years. In the multivariate Cox regression model with 13 independent covariates, initial Scr level, histological score, tonsillectomy, and high-dose methylprednisolone therapy had a significant impact on clinical remission, whereas proteinuria, age, sex, levels of hematuria, blood pressure, conventional steroid therapy, angiotensin-converting enzyme inhibitor therapy, and cyclophosphamide therapy had no significant effect. These findings indicate that interventions aimed at achieving clinical remission have provided encouraging results applicable to managing patients with IgA nephropathy.

Adolescent↗
PubMed2001

Chymase-dependent angiotensin II formation in the saphenous vein versus the internal thoracic artery.

OBJECTIVES: The great saphenous vein graft is known to be less patent than the internal thoracic artery graft. Recently, we reported that chymase-dependent angiotensin II formation plays an important role in the development of intimal hyperplasia in dog grafted veins. In this study we investigated the levels of angiotensin II-forming enzymes, angiotensin-converting enzyme, and chymase in human saphenous veins and internal thoracic arteries. METHODS: The saphenous vein and internal thoracic artery specimens were obtained from coronary artery bypass grafts of patients during surgical procedures (saphenous vein, n = 16; internal thoracic artery, n = 16). Activities of angiotensin-converting enzyme and chymase were determined by using the extract from the saphenous vein or internal thoracic artery. Sections of the saphenous vein or internal thoracic artery were stained with van Gieson's elastin stain and were immunostained with anti-human chymase antibody. RESULTS: The activities of angiotensin-converting enzyme in the saphenous vein and internal thoracic artery were 0.34 +/- 0.12 and 0.32 +/- 0.17 mU/mg protein, respectively, and the difference was not significant. The chymase activity in the saphenous vein was significantly higher than that in the internal thoracic artery (saphenous vein, 10.1 +/- 0.81 mU/mg protein; internal thoracic artery, 6.21 +/- 1.86 mU/mg protein). Chymase-positive cells in the saphenous vein were located in both the media and adventitia, and those in the internal thoracic artery were located only in the adventitia. The number of chymase-positive cells in the saphenous vein was about 2.6 times that in the internal thoracic artery. CONCLUSION: The chymase activity, but not the angiotensin-converting enzyme activity, was significantly higher in the saphenous vein, suggesting that the high levels of chymase activity may be related to the poorer performance of the saphenous vein for use as a bypass conduit.

Aged↗
PubMed2001

Purification and identification of N-glycolylneuraminic acid (Neu5Gc) from the holothuroidea Gumi, Cucumaria echinata.

N-Glycolylneuraminic acid (Neu5Gc), precious sialic acid which could not be synthesized by a chemical method, occurrs in the body of holothuroidea, Gumi Cucumaria echinata. Gumi contains 85% of total sialic acid, as Neu5Gc, in the body. Neu5Gc was purified from dry powder of the body using Dowex 1-x8 (HCOO* form) anion exchange chromatography after mild acid hydrolysis with 0.1 N trifluoroacetic acid. Using GC-MS and 1H-NMR spectroscopy, the purified Neu5Gc was correctly identified to be Neu5Gc. The purity of Neu5Gc was more than 99%. This is the first report of purification and identification of Neu5Gc from holothuroidea by using anion exchange chromatography, GC-MS, and 1H-NMR.

Animals↗
PubMed2001

Targeted disruption of stearoyl-CoA desaturase1 gene in mice causes atrophy of sebaceous and meibomian glands and depletion of wax esters in the eyelid.

Stearoyl-CoA desaturase (SCD) is a microsomal rate-limiting enzyme in the cellular synthesis of monounsaturated fatty acids (MUFA), mainly oleate (18:1) and palmitoleate (16:1), which are the major MUFA of membrane phospholipids, cholesterol esters and triglycerides. Three well-characterized isoforms of SCD, SCD1, SCD2 and SCD3, exist in mice. To investigate the physiologic functions of SCD1, we generated SCD1 null (SCD1-/-) mice. The skin and eyelid of SCD1-/- mice are deficient in triglycerides and cholesterol esters, and the eyelid also is deficient in wax esters. Furthermore, the eyelid and skin of SCD1-/- mice have higher levels of free cholesterol. SCD1-/- mice develop cutaneous abnormalities and narrow eye fissure with atrophic sebaceous and meibomian glands. Consumption of diets containing high levels of oleate, failed to restore the levels of triglycerides, cholesterol esters and wax esters in SCD1-/- mice to the levels found in the eyelid of wild-type mice. These results reveal a physiologic role of SCD in cholesterol homeostasis as well as in the de novo biosynthesis of cholesterol esters, triglycerides and wax esters required for normal skin and eyelid function.

Animals↗
PubMed2001

Autonomic insufficiency as a factor contributing to dialysis-induced hypotension.

BACKGROUND: Autonomic insufficiency is considered a factor that contributes to dialysis-induced hypotension (DIH). However, the relationship between the two conditions has not been fully elucidated. METHODS: We investigated 44 haemodialysis patients using [(123)I]-meta-iodobenzylguanidine (MIBG) scintigraphy and power-spectral analysis (PSA) of heart rate variability. The patients were divided into four groups: a diabetic group with DIH, a diabetic group without DIH, a non-diabetic group with DIH, and a non-diabetic group without DIH. In these groups the heart to mediastinum average count rate (H/M), MIBG washout rate, and low- and high-frequency components of PSA were compared. RESULTS: From the [(123)I]-MIBG scintigraphy, for both early and delayed images, H/M of the groups with DIH were lower than in groups without DIH, in both diabetics and non-diabetics (P<0.05). For the early images, H/M of the diabetic groups were lower than in the non-diabetic groups, in the groups both with and without DIH (P<0.01). For the delayed images, H/M of the diabetic group was lower than in the non-diabetic group, in the groups with DIH (P<0.05). The MIBG washout rate was the highest in the diabetic group with DIH (P<0.05 vs diabetic and non-diabetic groups without DIH). The PSA of heart rate variability showed a good discrimination of the low-frequency component between the non-diabetic patients with and without DIH (P<0.05). Mean ultrafiltration volume and its rate were not different among the four groups. CONCLUSION: Autonomic insufficiency is more severe in patients with DIH than in those without, and its degree may be enhanced in diabetic patients. For the management of DIH, special care should be addressed not only to dry weight but also to autonomic insufficiency.

3-Iodobenzylguanidine↗
PubMed2001

Clinical and endoscopic features of adult T-cell leukemia/lymphoma with duodenal involvement.

We describe three cases of adult T-cell leukemia/lymphoma (ATLL) with duodenal involvement and provide a review of the literature. The first case, a 74-year-old woman with acute subtype of ATLL, had multiple polypoid lesions from the bulbus extending into the descending portion of the duodenum. The second case, a 70-year-old man with lymphoma subtype of ATLL, had a polypoid tumor in the descending portion of the duodenum and multiple protruded lesions in the small and large intestines. The third case, a 67-year-old man with lymphoma subtype of ATLL, had a flat-elevated lesion in the descending portion of the duodenum, as well as a gastric ulcerated lesion. Biopsies from these lesions showed mucosal invasion of ATLL cells in each case. All patients received combination chemotherapy, which was successful in the first and third cases, accompanied by the disappearance of gastroduodenal lesions.

Adult↗
PubMed2001

Nonsurgical management of ruptured pseudoaneurysm in patients with hepatobiliary pancreatic diseases.

OBJECTIVE: Rupture of a pseudoaneurysm is an unusual complication after surgical and interventional treatments in patients with hepatobiliary pancreatic diseases. However, it occurs abruptly and often results in a lethal outcome. The aim of this study was to retrospectively analyze our experiences of cases of rupture of pseudoaneurysms for providing appropriate therapeutic planning. METHODS: Between 1985 and 1998, we observed ruptures of pseudoaneurysms in 14 of 910 patients with hepatobiliary pancreatic diseases--six after pancreaticoduodenectomy, three after hepatic resection, two after hepatopancreaticoduodenectomy, two after percutaneous transhepatic biliary drainage, and one after gastrojejunostomy. Thirteen of the 14 patients underwent emergency angiography and transcatheter arterial embolization (TAE) or infusion therapies, and one of the 13 patients underwent surgical hemostasis because of incomplete hemostasis with TAE. The other patient, who did not undergo emergency angiography, had surgical hemostasis initially. RESULTS: TAE achieved hemostasis in 11 of 13 patients (85%), but only incomplete hemostasis in the remaining two patients. Of these two patients, one underwent laparotomy, but died of multiple organ failure (MOF) at 6 days after surgical hemostasis. The other died at 1 day after emergency angiography. Ten of 11 patients who obtained complete hemostasis by means of TAE could later be discharged, but one patient died of liver failure, and/or MOF. One patient who underwent laparotomy initially without angiography died of MOF at 43 days after the operation. The onset of rupture of a pseudoaneurysm was a mean of 35.4 days (range 12-76) after surgical or interventional procedures. The warning prodromal symptoms were upper abdominal oppression, nausea, and backache before the rupture of pseudoaneurysms. Fever, leukocytosis. hyperbilirubinemia, anastomotic leak, and intraabdominal abscess were frequent persistent signs in these patients. CONCLUSIONS: If the warning prodromal symptoms appear in patients along with these persistent signs, the impending rupture of pseudoaneurysms should be suspected. Thereafter, a diagnostic angiography should be performed immediately to enable early diagnosis and embolization therapy for rupture of pseudoaneurysms when hemorrhagic episodes appear in these patients. Early detection and immediate embolization might bring about a favorable outcome in patients with hepatobiliary pancreatic diseases who encounter rupture of pseudoaneurysms after surgical and interventional treatments.

Adult↗
PubMed2001

Intraglomerular synthesis of complement C3 and its activation products in IgA nephropathy.

BACKGROUND: Complement activation is thought to be pathologically important in IgA nephropathy (IgAN). Although C3 deposition in the mesangium is found in IgAN, the origin of C3 is not clear. We recently demonstrated intraglomerular C3 synthesis in the human kidney; however, the activation and pathological role of locally synthesized C3 remains unclear. Here we performed nonradioactive in situ hybridization for C3 mRNA and immunohistochemistry for C3 and its activation products, such as C3d and membrane attack complex (MAC), to determine whether locally produced C3 in glomeruli was activated in IgA nephropathy. METHODS: Renal samples from 14 patients with IgAN and 5 with minimal change nephrotic syndrome (MCNS) were examined. Uninvolved portions of surgically removed kidneys with tumors served as normal controls. RESULTS: C3 mRNA was not detected in glomeruli in control tissue and MCNS, but was strongly expressed in resident glomerular cells of IgAN, including mesangial cells, glomerular epithelial cells and the cells of Bowman's capsule. Examination of serial sections disclosed that more than 70% of cells positive for C3 mRNA were also stained for C3 protein, C3d, and MAC. Double staining for in situ hybridization and immunohistochemistry also revealed that those C3 mRNA signals were present in intraglomerular cells positive for C3. The expression of C3 mRNA and MAC in glomeruli correlated significantly with the degree of mesangial matrix expansion. CONCLUSIONS: Our results demonstrated that locally synthesized C3 is activated in the glomeruli of IgAN and that its expression correlated with the severity of mesangial matrix expansion. These findings suggest that activation of C3 may be involved in tissue injury in IgAN through the formation of membrane attack complex.

Adolescent↗
PubMed2001

Prognosis of patients with rounded atelectasis undergoing long-term hemodialysis.

We present 4 patients undergoing hemodialysis in whom thoracic computed tomography (CT) suggested a diagnosis of rounded atelectasis (RA) with pleural effusion. The clinical setting and follow-up CT of all 4 patients confirmed this diagnosis. The pleural fluid of each appeared serosanguineous or hemorrhagic and predominantly consisted of lymphocytes. Biochemical analysis of this fluid revealed high levels of total protein, lactate dehydrogenase and glucose. Bacterial culture and polymerase chain reaction for Mycobacterium tuberculosis DNA was negative. Pleural biopsy specimens from 2 of the 4 patients showed evidence of fibrinous change and mesothelial cell hyperplasia. Pleural effusion from all 4 patients did not respond to either fluid restriction or aggressive hemodialysis-induced dehydration. The subsequent clinical course and thoracentesis were repeated, and in 1 patient, this was followed by tetracycline pleurodesis. However, 2 patients died during pre-pleurodesis and 1 died during post-pleurodesis, all due to respiratory failure. We propose that the clinical setting and follow-up thoracic CT and thoracentesis of patients receiving long-term hemodialysis confirmed a diagnosis of rounded atelectasis with uremic pleural effusion. We also propose that the prognosis of patients with refractory pleural effusion receiving long-term hemodialysis would be improved by early pleurodesis.

Aged↗
PubMed2001

Steroid pulse therapy combined with tonsillectomy in IgA nephropathy associated with diabetes mellitus.

Ten patients with biopsy-confirmed IgA nephropathy associated with diabetes mellitus underwent dietary weight control and three courses of intravenous pulses of methylprenisolone followed by prednisolone for 6-12 months and tonsillectomy. The average length of the follow-up period was 47.8 (range 30-96) months. As compared with pretreatment values, hematuria, proteinuria, body mass index, and hemoglobin A(1c) were significantly improved after treatment. There were no significant differences with regard to blood pressure and glycemic blood glucose control. There was no worsening of diabetic retinopathy and nephropathy. During steroid pulse therapy, the patients who were treated with insulin needed a higher dosage of insulin; after steroid pulse therapy, the dosage returned to baseline. Even patients with IgA nephropathy and diabetes mellitus could be treated with combined therapy and showed beneficial responses, it they succeeded in reducing body mass index.

Adult↗
PubMed2001

Expression of the endoplasmic reticulum molecular chaperone (ORP150) rescues hippocampal neurons from glutamate toxicity.

A series of events initiated by glutamate-receptor interaction perturbs cellular homeostasis resulting in elevation of intracellular free calcium and cell death. Cells subject to such environmental change express stress proteins, which contribute importantly to maintenance of metabolic homeostasis and viability. We show that an inducible chaperone present in endoplasmic reticulum (ER), the 150-kDa oxygen-regulated protein (ORP150), is expressed both in the human brain after seizure attack and in mouse hippocampus after kainate administration. Using mice heterozygous for ORP150 deficiency, exposure to excitatory stimuli caused hippocampal neurons to display exaggerated elevation of cytosolic calcium accompanied by activation of mu-calpain and cathepsin B, as well as increased vulnerability to glutamate-induced cell death in vitro and decreased survival to kainate in vivo. In contrast, targeted neuronal overexpression of ORP150 suppressed each of these events and enhanced neuronal and animal survival in parallel with diminished seizure intensity. Studies using cultured hippocampal neurons showed that ORP150 regulates cytosolic free calcium and activation of proteolytic pathways causing cell death in neurons subject to excitatory stress. Our data underscore a possible role for ER stress in glutamate toxicity and pinpoint a key ER chaperone, ORP150, which contributes to the stress response critical for neuronal survival.

Animals↗
PubMed2001

Pharmacokinetic-pharmacodynamic modelling of human insulin: validity of pharmacological availability as a substitute for extent of bioavailability.

A method for assessing the extent of bioavailability (EBA) of human insulin from pharmacological data was determined. The time course governing increases in the plasma concentration of immuno-reactive insulin (IRI), as well as its pharmacological effects (glucodynamics), was determined after the intravascular administration of varying doses of human insulin. Pharmacokinetic (PK), pharmacodynamic (PD), and link models were constructed to elucidate the quantitative relationship between plasma IRI levels and pharmacological effects. After extravascular administration of the test formulation, only the time course governing the observed pharmacological effects was determined. The pharmacological data was translated into theoretical plasma concentration data, using the PK-PD model. Following this, the area under the theoretical plasma concentration-time curve (AUC) of the test formulation was calculated. The EBA was then estimated against a reference (intravascular) formulation, using a conventional equation. Since the pharmacological effects of insulin were observed to be highly dosing-rate-dependent, the PD model used in this study was modified to apply over a wide range of infusion rates. The results of the PK-PD analysis indicate that the doses administered can be accurately predicted from pharmacological data. To validate this method, the EBAs of controlled release formulations (the Osmotic Mini Pumps) of insulin, subcutaneously administered to the rat, were estimated. The EBA values obtained (92-96%) fell within a reasonable range. The area under the effect-time curves (AUE) obtained following subcutaneous applications of the Osmotic Mini Pump were calculated in a model-independent manner, in addition to pharmacological availabilities (PA), which were estimated against the reference (intravascular) formulations. The estimated PA values varied from 312% to 78%, in accordance with the intravascular input rates of the reference formulations. This indicates that PA should not be used as a substitute for EBA, unless data involving similar intravascular dosing rates to that of the reference formulations is available.

Animals↗
PubMed2001

An orally active chymase inhibitor, BCEAB, suppresses heart chymase activity in the hamster.

We investigated the effects of a novel chymase inhibitor, BCEAB (4-[1-[[bis-(4-methyl-phenyl)-methyl]-carbamoyl]-3-(2-ethoxy-benzyl)-4-oxo-azetidine-2-yloxy]-benzoic acid). The IC50 value of BCEAB for purified human chymase was 5.4 nM, whereas BCEAB did not inhibit the angiotensin-converting enzyme, elastase and tryptase. In isolated dog arteries, the IC50 value of BCEAB for the angiotensin I-induced contraction in the presence of 1 microM lisinopril was 2.8 microM. In the hamster, the heart chymase activities were significantly suppressed to 42.0% and 26.9% 3 h after oral administration of 100 and 300 mg of BCEAB/kg of body weight, respectively. In conclusion, BCEAB is a useful chymase inhibitor for studying the role of chymase in vivo.

Angiotensin II↗
PubMed2001

Possible roles of cardiac chymase after myocardial infarction in hamster hearts.

The significance of cardiac chymase after myocardial infarction (MI) was evaluated using a hamster model of MI. At 1, 3, 7, 14, 28 and 56 days after MI, tissues were removed for measurements of angiotensin-converting enzyme (ACE) and chymase activities. The mean infarct size 3 days after left coronary artery ligation was 47.3 +/- 5.9% of the left ventricle circumference. The ratio of left ventricle weight to body weight was significantly increased from 3 days after MI. The level of plasma renin activity in the MI hamsters was significantly increased at the early phase of MI (1-3 days), while no significant changes in plasma ACE activity were observed. The ACE activity in the infarcted left ventricle was significantly increased starting from 3 days after MI and this increase was sustained up to 28 days. The chymase activity in the infarcted left ventricle was significantly increased starting from 1 day after MI and this increase was sustained up to 56 days. The number of chymase-positive mast cells in the infarcted left ventricle was significantly higher than in the sham group 3 and 7 days after operation. Treatment with an angiotensin (Ang) II type 1 receptor antagonist (candesartan cilexetil, 10 mg/kg per day) starting 3 days before the induction of MI significantly reduced the mortality rate during 14 days of observation following MI, whereas treatment with an ACE inhibitor (lisinopril, 20 mg/kg per day) did not. A significant improvement in hemodynamics (maximal negative and positive rates of pressure development, left ventricular systolic pressure and end-diastolic pressure, mean arterial blood pressure) was observed by the treatment with candesartan cilexetil, but not with lisinopril, 3 and 14 days after MI. These results suggested that Ang II produced by chymase may participate in the pathophysiologic state after MI in hamsters.

Angiotensin Receptor Antagonists↗
PubMed2001

Local angiotensin II-generating system in vascular tissues: the roles of chymase.

Roles of each angiotensin II producing enzymes of each of the angiotensin II-producing enzymes were reviewed based on experimental models. In vascular tissues, angiotensin II is potentially cleaved from angiotensin I by angiotensin converting enzyme (ACE) and chymase. It has been confirmed that vascular tissues of humans, monkeys, dogs and hamsters have a chymase-dependent angiotensin II-forming pathway. Much like other hypertensive models, hamster hypertensive models show high levels of vascular ACE activity, but not chymase activity. In hypertensive hamsters, administration of either an ACE inhibitor or an angiotensin II type 1 (AT1) receptor antagonist resulted in similar reductions in blood pressure, suggesting that chymase is not involved in the maintenance of high blood pressure in this model. In monkeys fed a high-cholesterol diet, ACE activity was increased in the atherosclerotic lesions, and an ACE inhibitor and an AT1 receptor antagonist prevented atherosclerosis to a similar degree, suggesting that ACE may be mainly involved in the development of atherosclerosis. After balloon injury in dog vessels, both ACE and chymase activities were locally increased about 3-fold in the injured arteries, and an AT1 receptor antagonist was effective in preventing the intimal formation, but an ACE inhibitor was ineffective. In dog grafted veins, the activities of chymase were increased 15-fold, but those of ACE were increased only 2-fold, and the intimal formation was suppressed by either an AT1 receptor antagonist or a chymase inhibitor. In the normal vascular tissues, ACE plays a crucial role for angiotensin II production, whereas chymase is stored in mast cells in an inactive form. Chymase acquires the ability to form angiotensin II following mast cells activation followed by mast cells activation by a strong stimulus such as occurs in catheter-injury or grafting. Together, these results indicate that chymase plays a major role in the vascular angiotensin II-generating system, particularly in cases of vascular injury.

Angiotensin II↗