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Biomedical subjects

S Nakajima

Publications and source records attributed to S Nakajima.

At least 73 records · Page 4Linked to original sources

Unimolecular metastable decompositions of gem-dimethoxyalkanes (RR'C(OCH(3))(2)) upon electron impact. I. Dimethoxymethane and 1, 1-dimethoxyethane

The unimolecular metastable decompositions of dimethoxymethane (CH(2)(OCH(3))(2), 1) and 1,1-dimethoxyethane (CH(3)CH(OCH(3))(2), 2) upon electron impact have been investigated by means of mass-analyzed ion kinetic energy (MIKE) spectrometry, collision-induced dissociation (CID) spectrometry and D-labeling techniques. Both molecular ions are formed at extremely low abundance. Sequential transfers of a methyl group and a hydrogen atom to an ether oxygen are observed during the decomposition of [M - H](+) ions from 1 and 2. The [M - H](+) ion from 2 also decomposes into the m/z 43 ion by the loss of dimethyl ether. Almost complete hydrogen exchange is observed prior to the loss of CH(4) from the m/z 45 ion ([M - OCH(3)](+)) of 1. The m/z 59 ions ([M - OCH(3)](+)) of 2 decompose competitively into the m/z 31 and 29 ions by the losses of C(2)H(4) and CH(2)O, respectively. The former loss occurs via two different fragmentation pathways. The relative abundances of the ions in the MIKE spectra increase with decreases in the total heat of formation (Sigma DeltaH(f)) of the ion plus the neutral fragment. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

Characterization of progressive changes in ZPC of the vitelline membrane of quail oocyte following oviductal transport.

The inner layer of the vitelline membrane of avian oocyte is equivalent to the zona pellucida of mammalian oocytes or to the vitelline envelope of amphibian oocytes. One of the two major glycoproteins in the inner layer of quail vitelline membrane, formerly called 33-kDa glycoprotein, is homologous to mammalian ZPC, one of the components of zona pellucida. Quail ZPC is found to have different mobilities on SDS-polyacrylamide gel electrophoresis depending on whether it is obtained from the preovulatory follicle or from the laid eggs. In order to characterize the progressive changes in the molecular size of quail ZPC during the oviductal transport, the inner layer isolated from the follicle was incubated in vivo in various regions of the oviduct and subjected to Western blot analysis with anti-quail ZPC antiserum. The quail ZPC of the inner layer incubated in infundibulum reduced its apparent molecular weight, exhibiting the same electrophoretic mobility as that of laid eggs. The similar reduction in molecular weight was observed after the in vitro incubation of the inner layer with the extracts of infundibulum. From the comparison of the N-terminal amino acid sequences, it was found that the first 26 residues of the quail ZPC in follicular oocytes are missing from the ZPC of laid eggs. In addition, lectin blot analysis suggested the modification of oligosaccharide chains during the oviductal transport. These results represent the first description in the avian oviduct of the presence of protease, which is similar to oviductin, a trypsin-like protease involved in the hydrolysis of a major component of the vitelline envelope of amphibian oocytes. Mol. Reprod. Dev. 55:175-181, 2000.

Amino Acid Sequence↗

Metastable decompositions of gem-dialkoxyalkanes upon electron impact. III. Diethoxymethane (CH(2)(OCH(2)CH(3))(2))

Unimolecular metastable decomposition of diethoxymethane (CH(2)(OCH(2)CH(3))(2), 1) upon electron impact has been investigated by means of mass-analyzed ion kinetic energy (MIKE) spectrometry and theD-labeling technique in conjunction with thermochemistry. The m/z 103 ion ([M - H](+) : CH(OCH(2)CH(3)) = O(+)CH(2)CH(3)) decomposes into the m/z 47 ion (protonated formic acid, CH(OH) = O(+)H) by consecutive losses of two C(2)H(4) molecules via an m/z 75 ion. The resulting product ion at m/z 47 further decomposes into the m/z 29 and 19 ions by losses of H(2)O and CO, respectively, via an 1,3-hydroxyl hydrogen transfer, accompanied by small kinetic energy release (KER) values of 1.3 and 18.8 meV, respectively. When these two elimination reactions are suppressed by a large isotope effect, however, another 1,1-H(2)O elimination with a large KER value (518 meV) is revealed. The m/z 89 ion ([M - CH(3)](+) : CH(2)(OCH(2)CH(3))O(+) = CH(2)) decomposes into the m/z 59 ion (CH(3)CH(2)O(+) = CH(2)) by losing CH(2)O in the metastable time window. The source-generated m/z 59 ion ([M - OCH(2)CH(3)](+) : CH(2) = O(+)CH(2)CH(3)) decomposes into the m/z 41 (CH(2) = CH(+)CH(2)) and m/z 31 (CH(2) = O(+)H) ions by losses of H(2)O and C(2)H(4), respectively, with considerable hydrogen scrambling prior to decomposition. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

Surgical management of ductus arteriosus aneurysm in adults.

Aneurysm of the ductus arteriosus is rare, especially in adults, and preoperative diagnosis is very difficult, requiring intraoperative diagnosis. A 71-year-old man was preoperatively diagnosed with ductus arteriosus aneurysm by computed tomographic scanning, magnetic resonance imaging, and aortography, which demonstrated a saccular aneurysm of the distal aortic arch. Under partial extracorporeal circulation, the aneurysm was replaced by an artificial vascular graft. The location and morphology of the aneurysm confirmed the preoperative diagnosis. The postoperative course was uneventful. Surgery for this condition is safe and is recommended the same as for common thoracic aortic aneurysm.

Aged↗

Interferon treatment on glomerulonephritis associated with hepatitis C virus.

We report on a 10-year-old girl with glomerulonephritis associated with hepatitis C virus infection, who was treated with interferon-alpha. On the first renal biopsy at 8 years of age, mild mesangial hypercellularity in a segmental to semiglobal pattern was present in all glomeruli. After 6 months interferon-alpha therapy, proteinuria diminished completely. However, mesangial proliferation was advanced on the second biopsy at 10 years of age. We concluded that the interferon-alpha was effective in the treatment of proteinuria despite the lack of pathological improvement.

Antiviral Agents↗

Botryoid Wilms tumor: case report and review of literature.

A rare case of botryoid Wilms tumor is presented. The main clinical manifestations were persistent low-grade fever, malaise, and proteinuria associated with microhematuria. Ultrasonography revealed an echogenic mass in the right kidney, and a contrast-enhanced mass was found in the dilated collecting system by contrast-enhanced computed tomography. The surgically resected tumor was a polypoid, light-yellow, glistening mass that occupied a large part of the renal pelvis and originated from the pelvicaliceal wall. Part of the tumor extended to the proximal ureter, resulting in hydronephrosis in the involved kidney. No parenchymal lesion was observed. Microscopic examination revealed epithelial, stromal, and blastemal components, which indicated Wilms tumor. Infection had occurred in the hydronephrotic kidney, which presumably had caused the major presenting symptoms. The prognosis of our patient and previously reported cases of botryoid Wilms tumor was good compared with that of typical Wilms tumor, since the botryoid type can be detected at an early stage.

Hematuria↗

Mutation analysis of two Japanese patients with Fanconi-Bickel syndrome.

Fanconi-Bickel syndrome (FBS), or glycogen storage disease type XI, is a rare autosomal recessive disorder characterized by hepatorenal glycogen accumulation, Fanconi nephropathy, and impaired utilization of glucose and galactose. Recently, this disease was elucidated to link mutations in the glucose transporter 2 (GLUT2) gene. Only three mutations in three FBS families have been reported. Therefore, it is important to elucidate mutations in the GLUT2 gene in FBS by answering the question of whether the syndrome is a single gene disease. In this report, we describe two patients in two unrelated families clinically diagnosed with FBS. No mutation in the entire protein coding region of the GLUT2 gene was detected in patient 1, which suggested that no mutation existed in the GLUT2 gene, or that some mutations had affected the expression of the GLUT2 gene. In patient 2, a novel homozygous nonsense mutation (W420X, Trp at codon 420 to stop codon) was detected. These results support the correlation between GLUT2 gene mutation and FBS syndrome. However, many patients must be analyzed to determine whether other genes are involved in FBS.

Adult↗

Inhibitory effect of TMK-688 on late asthmatic responses as well as T-cell and eosinophilic infiltration in guinea pigs with asthmatic reactions.

The effects of an oral anti-allergic agent, TMK-688, which inhibits 5-lipoxygenase, at doses of 3.2 and 10 mg/kg were studied in guinea pigs with dual-phase asthmatic response. We previously observed that pretreatment with TMK-688 inhibited the late asthmatic response (LAR) induced by ovalbumin inhalation exposure. The present study focused on the effect of TMK-688 on infiltration by T-cells and eosinophils. TMK-688 inhibited both T-cell and eosinophilic infiltration. These findings suggest that TMK-688 is effective in inhibiting infiltration of T-cells and eosinophilic chemotaxis, and thereby suppresses LAR.

Animals↗

Survey of recognition and utilization of guidelines for the diagnosis and management of bronchial asthma in Japan.

BACKGROUND: In Japan in 1993, the Japanese Society of Allergology (JSA) developed guidelines for diagnosis and management of asthma (JGL), which were based on the concept that asthma is a chronic inflammatory disorder of the airway. METHODS: This survey study was intended to investigate the recognition and utilization of JGL among physicians who had treated asthma. The survey comprised two methods: a quantitative mail survey and a qualitative door-to-door survey conducted by trained interviewers. RESULTS: In the mail survey, a total of 1028 physicians responded; 552 members of the JSA and 476 nonmembers. Ninety-four percent of JSA members were aware of adult asthma management guidelines, while 53% of nonmembers were aware of them. Although approximately half of the physicians, both members and nonmembers, found differences between the asthma management policies in JGL and their previous policies, most of them utilized JGL once they read it. In the qualitative door-to-door survey, 80-90% of physicians evaluated JGL as good after they read it. CONCLUSIONS: JGL was recognized and utilized by most JSA members, but only half of nonmember physicians were aware of JGL, although they utilized JGL after they read it. Further action to implement JGL among nonspecialist physicians is needed to improve management of asthma.

Adult↗

A double-blind, placebo-controlled steroid-sparing study with budesonide Turbuhaler in Japanese oral steroid-dependent asthma patients. Japanese Pulmicort Turbuhaler study group.

OBJECTIVE: The aim of this study was to evaluate the oral steroid-sparing capacity of budesonide Turbuhaler. METHODOLOGY: One hundred and thirteen oral steroid-dependent patients were treated for 6 months with placebo or budesonide 800 microg or 1600 microg daily. Every second week the oral steroid dose was reduced if asthma control permitted. RESULTS: The reductions in oral steroid doses were 9, 35 and 60% in the placebo and budesonide 800 microg and 1600 microg groups, respectively. Oral steroid treatment could be discontinued in 4% (placebo), 15% (800 microg) and 23% (1600 microg). Mean peak expiratory flow values increased by 21 and 24 L/min in the budesonide groups but decreased by 6 L/min in the placebo group. Asthma attack, activity and sleep scores remained unchanged showing maintained efficacy. Plasma cortisol levels increased and an adrenocorticotropic hormone test showed improved adrenocortical response in both budesonide groups, indicating improved safety. Adverse drug reactions were infrequent and mild in all study groups. CONCLUSION: Budesonide Turbuhaler, 800 microg and 1600 microg daily, resulted in a significant reduction in oral steroid usage in steroid-dependent patients. The effect was achieved with maintained asthma control together with improvements in lung and adrenal functions.

Administration, Inhalation↗

A double-blind, placebo-controlled dose-response study with budesonide Turbuhaler in Japanese asthma patients. Japanese Pulmicort Turbuhaler study group.

OBJECTIVE: The aim of this study was to investigate the dose-response for inhaled budesonide via Turbuhaler in Japanese patients with mild to moderate asthma. METHODOLOGY: Inhaled budesonide 100 microg, 200 microg, 400 microg or placebo was administered twice daily via Turbuhaler for 6 weeks, to 267 adult Japanese patients (mean age 51 years) with mild-to-moderate, non-steroid-dependent bronchial asthma, in a double-blind, placebo-controlled, randomized, parallel group study. The patients had to be symptomatic for more than 3 days/week and have an average morning peak expiratory flow (PEF) 50-80% of predicted normal value. RESULTS: The response to budesonide was rapid, all treatments showing a significant improvement in morning PEF after 1 week (P<0.05). During week 6, mean improvements of 15, 45, 53 and 71 L/min were observed for the placebo, 200 microg, 400 microg and 800 microg budesonide groups, respectively. Compared with placebo all improvements in the budesonide groups were statistically significant and a significant dose-response was demonstrated (P<0.001). The difference between the 200 microg and 800 microg doses was significant. Also, for several secondary efficacy variables (e.g. evening PEF, symptom score, treatment score, daily activity score and sleep score) significant dose-responses were shown. Other variables included the investigators' assessments of improvement and usefulness. They also showed statistically significant dose-response relationships and confirmed the rapid onset of action. Budesonide was well tolerated at all tested doses, with a low incidence of adverse events, all of which were minor in severity. CONCLUSIONS: Budesonide Turbuhaler in the doses 100 microg to 400 microg twice daily was effective, well tolerated and showed a rapid onset of action in patients with mild-to-moderate asthma. Dose-response was demonstrated for several variables of clinical efficacy.

Administration, Inhalation↗

Hypothetical pathophysiology of acute encephalopathy and encephalitis related to influenza virus infection and hypothermia therapy.

BACKGROUND: To establish a treatment strategy for acute encephalopathy and encephalitis associated with influenza virus infection, the pathophysiology of the disease was investigated through manifestations and laboratory findings of patients. PATIENTS AND METHODS: A child with central nervous system (CNS) complications during the course of influenza virus infection was analyzed in view of immunologic abnormalities. In addition, four children with acute encephalopathy and encephalitis were enrolled in the hypothermia treatment for the purpose of stabilizing the cytokine storm in the CNS. RESULTS: The CNS symptoms preceded the systemic progression to the failure of multiple organs (MOF) and disseminated intravascular coagulopathy (DIC). The mild hypothermia suppressed the brain edema on computed tomography (CT) scanning and protected the brain from the subsequent irreversible neural cell damage. CONCLUSION: The replicated viruses at the nasopharyngeal epithelium may disrupt the olfactory mucosa and gain access to the brain via the olfactory nerve system. The direct virus-glial cell interaction or viral stimulation of the glial cells induces the production and accumulation of the pro-inflammatory cytokines, especially tumor necrosis factor (TNF)-alpha, in the CNS. The cytokine storm results in neural cell damage as well as the apoptosis of astrocytes, due to the TNF-alpha-induced mitochondrial respiratory failure. The disruption of the blood-brain barrier progresses to the systemic cytokine storm, resulting in DIC and MOF. Mild hypothermia appears promising in stabilizing the immune activation and the brain edema to protect the brain from ongoing functional, apoptotic neural and glial damage and the systemic expansion of the cytokine storm.

Acute Disease↗

A global platelet test of thrombosis and thrombolysis detects a prothrombotic state in some patients with non-insulin dependent diabetes and in some patients with stroke.

Platelet aggregation and spontaneous thrombolytic activity were assessed in patients with non-insulin dependent diabetes and stroke using a shear-induced and agonist-induced platelet aggregation test. The Thrombotic Status Analyser (TSA), induces platelet-rich thrombus formation solely by shear forces, while whole blood platelet aggregometry measures platelet reactivity to different agonists. These tests were employed in the present study because in earlier studies they both demonstrated that platelet aggregability in healthy volunteers was unchanged with age. On the other hand, it is known that thrombolytic activity decreases with age in males, but not in females. In diabetic patients shear-induced platelet aggregability varied according to the stage of nephropathy but platelet aggregation to collagen was suppressed at all stages. Platelet reaction to shear stress was enhanced in stroke patients with haemorrhagic episodes but not in patients with lacunar infarction. In contrast, platelet reactivity to collagen was suppressed and changes in ADP-induced platelet aggregability were inconsistent. Suppressed thrombolysis was observed only in diabetes with minor renal defect. Fibrinogen was increased in diabetes with stage III and IV nephropathy. Fibrinopeptide A (FPA) and D-dimer were increased in stroke. Thus, the observed increase in fibrinogen, FPA and D-dimer is inconsistent with changes in platelet aggregability. Our present findings suggest that a shear-induced platelet aggregation test is superior to other tests such as agonist-induced platelet aggregation and thrombotic markers such as fibrinogen, FPA and D-dimer in detecting a prothrombotic state. It is concluded that elderly males may have a prothrombotic state not because of platelet hyper-aggregability but because of suppressed thrombolytic activity. On the other hand, a prothrombotic state in patients with non-insulin dependent diabetes and after stroke may be due to changes in age-independent platelet aggregability.

Adult↗

New oral dosage form for elderly patients. III. Stability of trichlormethiazide in silk fibroin gel and various sugar solutions.

The hydrolysis of trichlormethiazide (TCM) in silk fibroin gel (SFG) prepared in various sugar solutions (such as ribose, fructose, mannose, and glucose solutions) was determined. The hydrolysis rate of TCM differed with the variety of sugars utilized in this study; that is, it decreased in the following order: ribose > fructose > mannose > glucose. To investigate the relationship between the hydrolysis rate of TCM and the physicochemical properties of the sugar molecule, the amount of unfrozen water of sugar molecules was calculated from differential scanning calorimetry (DSC). The amount of unfrozen water increased with an increase in the number of the equatorial OH groups n(e-OH) per sugar molecule that are able to hydrate favorably to the surrounding water molecules. The hydrolysis rate constant decreased with increase in n(e-OH); glucose, having a large n(e-OH) in this study could effectively stabilize TCM.

Administration, Oral↗

Stability of the powdered dosage form prepared by unsealing the capsules: water vapor sorption and discoloration of the powdery contents of clorazepate dipotassium capsules.

The hygroscopicity of the contents of clorazepate dipotassium (Mendon) capsules (CM) was investigated by storage at various relative humidities (RHs). The CM adsorbed water vapor significantly at more than 75% RH. At the same time, a marked discoloration of CM from white to yellow was also observed during storage. On the basis of differential scanning calorimetry (DSC) and Fourier transform (FT) Raman spectroscopy, the discoloration seemed to be due to the change in clorazepate dipotassium to nordiazepam and other substances. It was found that, when opening of the Mendon capsule is necessary to prepare the powdered dosage form, the CM should be stored below 60% RH to avoid the adsorption of water vapor and discoloration.

Anti-Anxiety Agents↗