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Biomedical subjects

S Nakano

Publications and source records attributed to S Nakano.

At least 289 records · Page 16Linked to original sources
PubMed1996

Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit.

We describe the genetic and kinetic defects for a low-affinity fast channel disease of the acetylcholine receptor (AChR) that causes a myasthenic syndrome. In two unrelated patients with very small miniature end plate (EP) potentials, but with normal EP AChR density and normal EP ultrastructure, patch-clamp studies demonstrated infrequent AChR channel events, diminished channel reopenings during ACh occupancy, and resistance to desensitization by ACh. Each patient had two heteroallelic AChR epsilon subunit gene mutations: a common epsilon P121L mutation, a signal peptide mutation (epsilon G-8R) (patient 1), and a glycosylation consensus site mutation (epsilon S143L) (patient 2). AChR expression in HEK fibroblasts was normal with epsilon P121L but was markedly reduced with the other mutations. Therefore, epsilon P121L defines the clinical phenotype. Studies of the engineered epsilon P121L AChR revealed a markedly decreased rate of channel opening, little change in affinity of the resting state for ACh, but reduced affinity of the open channel and desensitized states.

Acetylcholine↗
PubMed1996

Determination of ultratrace amounts of copper (II) by its catalytic effect on the oxidative coupling reaction of 3-methyl-2-benzothiazolinone hydrazone with N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline.

A spectrophotometric method was developed for the determination of ultratrace amounts of copper(II) based on its catalytic effect on the oxidative coupling reaction of 3-methyl-2-benzothiazolinone hydrazone with N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline to produce an intensely coloured dye (lambda(max) = 525 nm) in the presence of hydrogen peroxide. In this reaction, pyridine acted as an effective activator for the catalysis of copper(II). By measuring the absorbance of the dye, copper(II) can be determined at the 0.002-0.1 ng cm(-3) (3.1 x 10(-11)-1.6 x 10(-9) mol dm(-3) level. The relative standard deviation for ten determinations of 0.06 ng cm(0-3) of copper(II) was 2.6%. The proposed method was successfully applied to the determination of copper(II) in tap water and biological material.

Aniline Compounds↗
PubMed1996

New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome.

Mutations in genes encoding the epsilon, delta, beta and alpha subunits of the end plate acetylcholine (ACh) receptor (AChR) are described and functionally characterized in three slow-channel congenital myasthenic syndrome patients. All three had prolonged end plate currents and AChR channel opening episodes and an end plate myopathy with loss of AChR from degenerating junctional folds. Genetic analysis revealed heterozygous mutations: epsilon L269F and delta Q267E in Patient 1, beta V266M in Patient 2, and alpha N217K in Patient 3 that were not detected in 100 normal controls. Patients 1 and 2 have no similarly affected relatives; in Patient 3, the mutation cosegregates with the disease in three generations. epsilon L269F, delta Q267E and beta V266M occur in the second and alpha N217K in the first transmembrane domain of AChR subunits; all have been postulated to contribute to the lining of the upper half of the channel lumen and all but delta Q267E are positioned toward the channel lumen, and introduce an enlarged side chain. Expression studies in HEK cells indicate that all of the mutations express normal amounts of AChR. epsilon L269F, beta V266M, and alpha N217K slow the rate of channel closure in the presence of ACh and increase apparent affinity for ACh; epsilon L269F and alpha N217K enhance desensitization, and epsilon L269F and beta V266M cause pathologic channel openings in the absence of ACh, rendering the channel leaky, delta Q267E has none of these effects and is therefore a rare polymorphism or a benign mutation. The end plate myopathy stems from cationic overloading of the postsynaptic region. The safety margin of neuromuscular transmission is compromised by AChR loss from the junctional folds and by a depolarization block owing to temporal summation of prolonged end plate potentials at physiologic rates of stimulation.

Adolescent↗
PubMed1996

Myofibrillar myopathy with abnormal foci of desmin positivity. I. Light and electron microscopy analysis of 10 cases.

A number of myopathies whose common denominator is abnormal foci of desmin positivity have been described under the rubrics of spheroid body myopathy, cytoplasmic body myopathy, Mallory body myopathy, myopathy with granulofilamentous inclusions, desmin storage myopathy, and intermediate filament myopathy. In this study we reevaluate the light microscopic and ultrastructural features of the myopathy with abnormal foci of desmin positivity. In 10 cases of the disease, ultrastructural analysis reveals 2 major types of lesions: (a) foci of myofibrillar destruction and (b) hyaline structures that appear as spheroidal bodies on electron microscopy. The foci of myofibrillar destruction consist of fiber areas containing disrupted myofilaments, Z-disk-derived bodies, dappled dense structures of Z-disk origin, and streaming Z-disks that are sometimes adjacent to lakes of dense material. The spheroid bodies are composed of compacted and degraded myofibrillar elements. Membrane-bound vacuoles harboring degenerating membranous organelles are a less frequent and probably secondary abnormality. None of the lesions in muscle comprise 8 to 10 nm intermediate filaments. The findings imply that spheroid body myopathy, cytoplasmic body myopathy, Mallory body myopathy, and myopathy with granulofilamentous inclusions are consequences of a single or closely related pathologic processes. Because the common denominator appears to be focal dissolution of the myofibrils followed by accumulation of the products of the degradative process, we propose the term myofibrillar myopathy to cover the observed spectrum of pathologic changes.

Adult↗
PubMed1996

Enhanced tumor uptake of carboplatin and survival in glioma-bearing rats by intracarotid infusion of bradykinin analog, RMP-7.

OBJECTIVE: Intracarotid infusion of the bradykinin analog, RMP-7, can increase permeability in brain tumor capillaries. This study sought to determine the following: 1) the unidirectional transport, Ki, of radiolabeled [14C]carboplatin into brain tumors with either intravenous or intracarotid RMP-7 infusions; 2) the duration and extent of increased permeability in tumor capillaries during continuous RMP-7 infusions; and 3) the effect on survival of carboplatin combined with RMP-7 treatment in rats with gliomas. METHODS: Wistar rats with RG2 gliomas were used, and a unidirectional transfer constant, Ki, was determined using quantitative autoradiography. In the survival study, the rats were treated with intra-arterial carboplatin and RMP-7 at Days 5 and 7 after tumor implantation. RESULTS: Intracarotid infusion of RMP-7 for 15 minutes increased the transport of [14C]carboplatin to tumors by 2.7-fold, as compared with saline infusion alone (P < 0.001). The transports of [14C]dextran and [14C]carboplatin into tumors were significantly higher with 15 minutes of intracarotid infusion of RMP-7 (0.1 microgram/kg/min), compared to those with 10-, 30-, or 60-minute infusions (P < 0.01). Rats treated at Days 5 and 7 after tumor implantation with carboplatin alone (10 mg/kg) exhibited a modest increase in survival at 31 days (37%, compared to < 10% of controls), while those given the combination of carboplatin with RMP-7 exhibited a significantly higher survival rate (74%). CONCLUSION: Intracarotid infusion of RMP-7 can selectively increase transport of carboplatin into brain tumors and results in higher survival in rats with gliomas. These findings support the use of intracarotid infusion of RMP-7 to enhance the delivery of carboplatin to patients with malignant brain tumors.

Animals↗
PubMed1996

Prediction of hemorrhagic complications after thrombolytic therapy for middle cerebral artery occlusion: value of pre- and post-therapeutic computed tomographic findings and angiographic occlusive site.

OBJECTIVE: To evaluate the usefulness of pre- and post-therapeutic computed tomographic (CT) findings in predicting hemorrhagic complications, we retrospectively examined 35 patients treated with intra-arterial thrombolytic therapy for middle cerebral artery (MCA) occlusion. METHODS: The presence or absence of early CT findings (loss of the insular ribbon, obscuration of the lentiform nucleus, and cortical effacement) and the presence and location of extravasation of contrast medium were evaluated on pre- and post-therapeutic CT scans, respectively. According to the angiographic occlusive site, the patients were classified into the following three groups: Group 1 (n = 13), MCA trunk occlusion involved lenticulostriate arteries; Group 2 (n = 11), occlusion of the MCA trunk without involvement of the lenticulostriate arteries; Group 3 (n = 11), occlusion of a branch of the MCA. Hemorrhagic complications (hemorrhagic transformation and/or massive brain swelling) were evaluated by reviewing CT scans obtained 3 to 14 days after thrombolytic therapy. RESULTS: No patient without extravasation (n = 17) showed hemorrhagic complications, and extravasation is the most useful finding in predicting hemorrhagic complications. There was significant correlation between extravasation and hemorrhagic complications (P < 0.01). In Groups 1 and 2, there was also significant correlation between early CT findings and hemorrhagic complications (P < 0.01), indicating that early CT findings are also useful in predicting hemorrhagic complications. In Group 1, 10 of 13 (76.9%) patients had both early CT findings and extravasation, and 6 of these 10 patients had hemorrhagic complications with clinical deterioration, suggesting the difficulty of thrombolytic therapy in this group. On the contrary, in Group 2, 8 of 11 (72.7%) patients had neither early CT findings nor extravasation and none of these 8 patients had hemorrhagic complications. In Group 3, however, early CT findings and extravasation had no correlation. Because the affected area was small in this group, it was difficult to evaluate cortical effacement. Although negative early CT findings did not always mean absence of extravasation and hemorrhagic complications in this group, the patients with hemorrhagic complications did not clinically deteriorate because of the small affected area. CONCLUSION: Hemorrhagic complications could be predicted by evaluation of angiographic occlusive site and pre- and post-therapeutic CT findings.

Aged↗
PubMed1996

Effects of MCI-727 on pancreatic exocrine secretion and acute pancreatitis in two experimental rat models.

The effects of a newly developed compound having antiulcer action, (Z)-2-(4-methylpiperazin-1-yl)-1-[4-(2-phenyl-ethyl)phenyl]-eth anone oxime hydrochloride monohydrate (MCI-727), on pancreatic exocrine secretion were studied in anesthetized rats and evaluated its preventive and therapeutic effects on acute pancreatitis in two experimental rat models. Intraduodenal administration of MCI-727 [25, 50, or 100 mg/kg body weight (wt)] stimulated a dose-dependent increase in pancreatic juice and bicarbonate output without increasing the protein output or plasma cholecystokinin concentration. MCI-727-stimulated pancreatic exocrine secretion was completely abolished by antisecretin serum but not by the cholecystokinin receptor antagonist loxiglumide (50 mg/kg body wt/h) or cholinergic receptor antagonist atropine (100 mu g/kg body wt/h). In rats with acute pancreatitis induced by four subcutaneous injections of 20 mu g/kg body wt cerulein at hourly intervals over 3 h, MCI-727 administered orally at a dose of 100 mg/kg body wt 30 min before the first cerulein injection significantly reduced the increases in serum amylase and lipase activity and pancreatic wet weight and induced improvements in the results of histologic examination. Moreover, when given 30 min before and 90 min after the first cerulein injection, MCI-727 had even more dramatic protective effects on all these parameters. In addition, even when administered immediately after the last cerulein injection, MCI-727 effectively ameliorated all these alterations of acute pancreatitis. However, MCI-727 had no apparent beneficial effects on the biochemical and histologic alterations of acute pancreatitis in the severe form induced by retrograde intraductal injection of 1.0 ml/kg body wt of 4% sodium taurocholate. These findings suggest that oral administration of MCI-727 stimulates pancreatic exocrine secretion by endogenous secretin release and that it has therapeutic as well as preventive effects on mild forms of acute pancreatitis in rats.

Acute Disease↗
PubMed1996

Painless thyroiditis occurring during long-term treatment with interferon alfa in a patient with chronic active hepatitis C.

We describe here painless thyroiditis during interferon (IFN) therapy in a 65-year-old man with chronic active hepatitis C. The patient had hypothyroidism in the late stage of a 24-week course of treatment with IFN-alpha. After cessation of the treatment a small, firm goiter was noticed, and chronic focal thyroiditis was diagnosed histologically. Analyses of the stock serum samples drawn before, during, and after IFN-alpha therapy revealed transient hyperthyroidism followed by transient hypothyroid states with aggravation of antithyroid hormone antibody titers. These findings suggest that long-term IFN-alpha therapy caused painless thyroiditis with aggravation of autoimmunity in our patient with preexisting chronic thyroiditis.

Aged↗
PubMed1996

Long-term administration of natural interferon-alpha in patients with chronic hepatitis C: relationship to serum RNA concentration, HCV-RNA genotypes, histological changes and hepatitis C virus.

To virologically assess the efficacy of interferon therapy in chronic hepatitis C, either 5 or 10 MU/day natural interferon-alpha (IFN alpha) was administered to 57 patients with chronic hepatitis C for 38 weeks. A complete and sustained response (CR-SR), as evidenced by the absence of serum hepatitis C virus (HCV)-RNA during the administration period and at 6 months after the final administration of IFN alpha and normal GPT level at 6 months after final administration, occurred in 42.6% (23/54) of subjects. Liver tissue was histologically evaluated using the histological activity index (HAI) score before and after the administration period. In CR-SR cases, significant improvements (P < 0.01) occurred in periportal necrosis, intralobular necrosis, portal inflammation and total score. A comparison, by HCV genotypes, revealed that CR-SR occurred in 60% (9/15) of subjects with type 2a and 30.3% (10/33) of subjects with type 1b. A comparison by virus concentration revealed that CR-SR occurred in 71.4% (15/21) of those subjects having a virus concentration of < 10(5) copies/mL, but in only 24.2% (8/33) of those having a virus concentration of > 10(5) copies/mL. Analysis by a multiple logistic model revealed a strong correlation between the therapeutic effect of interferon therapy and the pre-administration virus concentration (P = 0.0061) and genotype (P = 0.0015). These results suggest that the pre-administration virus concentration and genotype are both key factors affecting the therapeutic effect of interferon therapy in chronic hepatitis C and that the therapeutic effect of interferon is satisfactorily high, irrespective of virus concentration, in subjects with type 2a HCV, but varies depending on virus concentration in subjects with type 1b.

Aged↗
PubMed1996

Estimation of usefulness of N-butyl-2-cyanoacrylate-lipiodol mixture in transcatheter arterial embolization for urgent control of life-threatening massive bleeding from gastric or duodenal ulcer.

We estimated the usefulness of a mixture of N-butyl-2-cyanoacrylate (NBCA) with lipiodol for transcatheter arterial embolization (TAE) used to control massive bleeding from gastric or duodenal ulcer. Thirty patients who had gastric or duodenal ulcers and massive bleeding that was uncontrollable by endoscopic procedures were included in this study. All patients were subjected to TAE (without NBCA in 23 and with NBCA in seven patients). Coils and/or gelfoam were also used. The achievement of haemostasis, occurrence of rebleeding and the time taken for TAE were compared between patients who received TAE without and with NBCA. Eighteen of 23 patients (78.3%) who received TAE without NBCA and six of seven patients (85.7%) who underwent TAE with NBCA achieved complete haemostasis without rebleeding. The time for TAE was significantly shorter in patients who received NBCA compared with those who did not (P = 0.0095). TAE using NBCA or a combination of NBCA and coils achieved a rapid, complete embolization regardless of vascular distribution or arterial diameter. Thus NBCA is considered to be useful as a secondary embolization material in TAE that is urgently conducted to control massive bleeding from gastric or duodenal ulcers.

Adult↗
PubMed1996

Protein-losing enteropathy due to intestinal lymphangiectasia accompanied by mesenteric lymph node fibrosis.

An autopsy case of a 74-year-old man suffering from edema in the legs and diagnosed as protein-losing enteropathy due to intestinal lymphangiectasia is presented. He underwent a radical operation and radiotherapy for esophageal carcinoma at age 65 years and the onset of protein-losing enteropathy was at age 70. Postmortem examination disclosed widespread abnormalities of the duodenal and small intestinal lymphatics and mesenteric lymph node fibrosis. The mucosal lymphatic capillaries were markedly dilated. In the submucosal and serosal layers, the lymphatic vessels showed marked dilatation in some areas and fibrous occlusion with very thick muscle layers in others. All these lymphatic changes were presumed to be attributable to a reactive process secondary to lymph congestion, which it is suggested, was caused by the mesenteric lymph node fibrosis.

Aged↗
PubMed1996

Surgical modulation of the natural course of collateral circulation in chronic ischemic patients.

The purpose of this study was to evaluate hemodynamic compromise in terms of baseline CBF and CRC in patients with chronic cerebral occlusive lesions and its modulation by a superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis. The study subjects were 10 healthy volunteers and 49 chronic ischemic patients with stenosis or occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA). The hemodynamics were measured using stable xenon enhanced computed tomographic CBF measurement with the acetazolamide challenge. The compromised hemodynamics in patients with chronic steno-occlusive lesions did not improve during their natural course after two months. STA-MCA bypass modulated hemodynamic compromise in the ischemic patients. We recommend STA-MCA bypass for patients with reduced CRC, regardless of whether baseline CBF is reduced or normal. Hemodynamic classification using a combination of baseline CBF values and CRC values is useful for evaluating cerebral hemodynamics and for choosing the best treatment for cerebral ischemia with occlusive lesions.

Adult↗
PubMed1996

Modulation of cerebral hemodynamics by surgical revascularization in patients with moyamoya disease.

The purpose of this study was to evaluate hemodynamic compromise in the patients with moyamoya disease and surgical modulation of the hemodynamics using stable xenon enhanced computed tomographic CBF measurement with the acetazolamide challenge. The study group consisted of 15 preoperative cases and 17 postoperative cases. In the preoperative group, regional resting cerebral blood flow (rCBF) and regional cerebrovascular reserve capacity (rCRC) were reduced. The reduction was more prominent in the anterior circulation than in the posterior circulation. In the postoperative group, rCBF and rCRC were still low in the anterior circulation. Revascularization increased the resting CBF but did not change the CRC. Postoperative CBF did not increase in adults but increased in children. These findings suggest that the misery perfusion state may be present only in the child's brain. Measurement of CBF and CRC is useful to evaluate the hemodynamics of moyamoya disease.

Acetazolamide↗
PubMed1996

Effect of angiotensin converting enzyme inhibitor on chronic ischemic patients.

Most of patients with cerebrovascular disease are associated with hypertension. Hypertension induces progressive atheromatous changes in cerebral arteries, and often causes steno-occlusive lesions of cerebral arteries. Angiotensin converting enzyme (ACE) inhibitor cilazapril is one of the antihypertensive drugs. It was reported that cilazapril improved resting cerebral blood flow (CBF) and cerebrovascular reserve capacity (CRC) in experimental studies. In this clinical study, the authors investigated whether long-term treatment with cilazapril could improve CBF and CRC in patients with steno-occlusive lesions of the major cerebral arterial trunk, measured by stable xenon computerized tomography (Xe-CT) with acetazolamide challenge. On the other hand, CBF and CRC in the calcium blocker-treated patients were measured in the same way. CBF did not change after long-term treatment with both cilazapril and calcium blocker. In the cilazapril-treated group, CRC was increased significantly (p < 0.05). However, CRC did not change in the calcium blocker-treated group. It was recognized that long-term treatment with cilazapril did not decrease CBF and improved CRC in patients with occlusive lesions of the major cerebral arterial trunk.

Acetazolamide↗
PubMed1996

Hypertension and unilateral renal ischemia (Page kidney) due to compression of a retroperitoneal paraganglioma.

We describe a 17-year-old hypertensive man with a left abdominal mass on the computed tomographic scan. Radiologic studies revealed a large tumor near the left renal hilus, resulting in renal compression and displacement toward the posterolateral abdominal cavity. Aortography excluded stenosis of the renal arterial vessels. Plasma and urinary catecholamines were normal and plasma renin activity (PRA) was high. The left renal vein renin was 2.1-fold higher than the right one. After resecting the tumor including the left kidney and adrenal, high blood pressure and elevated PRA returned to normal. Histologically, the tumor was a paraganglioma, and the affected kidney showed hyperplasia of the juxtaglomerular apparatus. Thus, the hypertension in our patient was probably due to renal ischemia extrinsically compressed by a non-functioning retroperitoneal paraganglioma (Page kidney).

Adolescent↗