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Biomedical subjects

M Nakazawa

Publications and source records attributed to M Nakazawa.

At least 235 records · Page 13Linked to original sources

Ocular findings in patients with autosomal dominant retinitis pigmentosa and transversion mutation in codon 244 (Asn244Lys) of the peripherin/RDS gene.

OBJECTIVE: To identify phenotypic characteristics of a certain mutation in the peripherin/RDS gene. DESIGN: Case reports with clinical features and results of fluorescein angiography, electroretinography, kinetic visual field testing, dark adaptometry, and DNA analysis. SETTING: University medical center. PATIENTS: We studied the ocular findings in eight members of a Japanese family with autosomal dominant retinitis pigmentosa and cytosine-to-adenine transversion at the third nucleotide in codon 244 of the peripherin/RDS gene. This mutation resulted in a substitution of lysine for asparagine in amino acid 244 of peripherin/RDS, a photoreceptor-specific glycoprotein. RESULTS: Clinical findings of each affected member in this family showed a marked intrafamilial similarity, which may provide the natural course of the phenotype produced by the Asn244Lys mutation. Characteristic features include diffuse pigmentary retinal degeneration in the midperipheral and peripheral fundi associated with macular degeneration in the later stage, starting with bull's-eye maculopathy, and severely deteriorated electroretinographic findings in both rods and cones, even in the early stage. CONCLUSION: The mutation at codon 244 of the peripherin/RDS gene causes both rod and cone degeneration, although the precise mechanism of retinal degeneration is currently unknown.

Adult↗

Effect of reserpine on 5-hydroxytryptophan (5HTP)-immunoreactive neurons in the rat brain.

By immunohistochemistry of rat brain in conjunction with a specific antibody against 5-hydroxytryptophan (5HTP), we examined immunoreactivity to 5HTP in neurons, from which 5-hydroxytryptamine (5HT; serotonin) was depleted by reserpine treatment. The distribution patterns of 5HTP-positive neurons overlapped with those of 5HT neurons. Treatment with reserpine (5 mg/kg, 90 min before death) caused a complete suppression of 5HT-positive staining, but 5HTP-immunostaining remained in perikarya of the nuclei raphe dorsalis, centralis superior and obscurus. Treatment with reserpine (25 mg/kg, 90 min before death) suppressed the 5HTP-immunoreaction in certain perikarya (e.g. of the nucleus raphe dorsalis) and fibres; however, 5HTP-immunostaining remained in perikarya of the nuclei centralis superior and raphe obscurus. This suggests that these neurons synthesize more 5HTP by a process which appears to be stimulated by reserpine.

5-Hydroxytryptophan↗

Intravascular stents for management of pulmonary artery and right ventricular outflow obstruction.

This study was performed to determine the efficacy of balloon-expandable stents in the treatment of branch pulmonary artery-stenoses and conduit stenosis in children. A total of eight stainless steel stents were implanted in seven patients. Three patients had tetralogy of Fallot with pulmonary artery stenosis following total correction, one patient had conduit stenosis following correction of transposition of the great arteries, one patient had intra-cardiac conduit stenosis after septation for single left ventricle, and two patients had pulmonary artery stenosis after Fontan operation. Six stents were placed in the branch pulmonary arteries, one in the extracardiac conduit, and one in the intracardiac conduit. The mean age at implantation was 13 +/- 3 years and the mean weight 37 +/- 12 kg. Follow-up time ranged from 0.3-2 years. The diameter of pulmonary arteries with stenoses increased from 5.6 +/- 2.2 mm to 10.6 +/- 1.8 mm (n = 7). The systolic pressure gradient decreased from 56 +/- 26 mmHg to 22 +/- 16 mmHg (n = 5). No embolization or thrombotic event has been noted. One stent placed in the intracardiac conduit was compressed and fractured. These data indicate that balloon-expandable stents are useful in the treatment of pulmonary artery branch stenoses and extracardiac conduit stenosis in children. The use of stents for intracardiac stenosis may result in stent fracture.

Adolescent↗

Asynchronous volume changes of the two ventricles after Fontan operation in patients with a biventricular heart.

Coordinated contraction of the ventricle is an important determinant of pump function, which seems to be particularly important in Fontan circulation with one pumping ventricle. We analyzed the synchronism of contraction of the two ventricles in 11 patients with a biventricular heart who had undergone Fontan operation. Curves representing ventricular volume changes in a cardiac cycle measured on angiograms were smoothed and divided into 20 segments. We calculated the number of segments of the same directional volume changes (synchronous changes) between the two ventricles (synchronous ratio). We also calculated the total volume of the two ventricles (the two as one whole ventricle) by adding their volumes in each segment and calculated the ratio (stroke volume ratio) of the aortic stroke volume from the whole ventricle to the sum of stroke volumes of the morphological right and left ventricles. If the two ventricles ejected the blood in a completely synchronous manner, these ratios should be 1.0. In seven patients with synchronous ratios of 0.75 or greater and a stroke volume ratio of greater than 0.95, the cardiac index was 3.2 +/- 0.3 l/min/m2, the maximum total volume (corresponding to end-diastolic volume) was 106 +/- 45% normal, and the ejection fraction was 0.44 +/- 0.10. In four patients with ratios of less than 0.70 and 0.95, respectively, the parameters were 2.4 +/- 0.5 (P < 0.05), 193 +/- 92%, and 0.33 +/- 0.08, respectively. The synchronous ratio was inversely correlated with cardiac output. In conclusion, synchronism of the cardiac cycle of the two ventricles affects Fontan circulation in patients with a biventricular heart.

Adolescent↗

Automated collection of conditioned medium from organotypically cultured brain slice.

For the analysis of neural activity over a long period of time, the organotypic culture of mammalian brain slices provides excellent specimens. To effectively utilize the slice culture, we developed a device for automatic sampling of the culture medium. This device is a computer-controlled combination of a multichannel peristaltic pump to remove the media from the glass culture containers, a fraction collector designed to allow quick freezing of the samples, and a multichannel syringe pump to deliver new media to the containers. Using this device, substances released as results of neural activities can be collected at regular intervals over several days. We monitored the circadian release of arginine-vasopressin from cultured suprachiasmatic nuclei. We also monitored tonic releases of lactate dehydrogenase from cultured hippocampi phasically treated with an excitotoxin and from those transiently deprived of oxygen/glucose.

Animals↗

Experimental infection of young chicks with attaching and effacing Escherichia coli.

Young chicks were inoculated with six different strains of attaching and effacing Escherichia coli isolated from the feces of calves, pigs, chicks, and humans. Colibacilli of some serotypes had colonized the cecum of chicks by 7 days after inoculation. The characteristic lesions associated with bacterial attachment were also seen on the mucosal surface of the cecum. Electron microscopy revealed numerous colibacilli closely attached to the surface membrane of enterocytes. Cell membranes formed cups and pedestals at the base of the attached bacilli. The results of this study support the conclusion that young chicks can be used as a model for the study of the lesions caused by attaching and effacing E. coli strains.

Animals↗

[Research and development of ozagrel, a highly selective inhibitor of TXA2 synthase].

Highly selective inhibitors of thromboxane (TX) A2 synthase were noted as a therapeutic agent for ischemic heart diseases, thromboembolic disorders, cerebral circulatory disorders, and asthma. The 1-substituted imidazoles and beta-substituted pyridines showed high inhibitory potency on TXA2 synthase. The structure-activity relationships of the imidazole and pyridine derivatives as inhibitors of TXA2 synthase were investigated. Introduction of various substituents into the carboxy-bearing side chain of 1-(7-carboxyheptyl) imidazole and beta-(7-carboxyheptyl) pyridine was found to increase the inhibitory potency. The length of the side chains with the phenylene group was optimum in the region of 8.5 to 10 A for the inhibitory potency on TXA2 synthase. Among the tested imidazole and pyridine derivatives, (E)-4-(1-imidazolylmethyl)cinnamic acid (44) and (E)-3-[4-(3-pyridylmethyl)phenyl]-2-methylacrylic acid (56) showed the highest potency (IC50 = 1.1 x 10(-8) and 3 x 10(-9) M). The inhibition by these derivatives was highly selective for TXA2 synthase, since other enzymes which are involved in the arachidonic acid cascade, such as fatty acid cyclooxygenase, 5-lipoxygenase, prostacyclin (PGI2) synthase, and PGE2 isomerase were not affected. On the basis of the results obtained from the pharmacological, physicochemical and toxicological studies on the two compounds (44 and 56), (E)-4-(1-imidazolylmethyl) cinnamic acid (44; OKY-046, ozagrel) was selected as the best compound of highly selective inhibitors of TXA2 synthase. The pharmacological properties of ozagrel are as follows. The inhibition of TXA2 synthase by ozagrel was more effective on human and rabbit enzymes than those of other species. Ozagrel increased 6-keto-PGF1 alpha, one of stable metabolites of PGI2, in various isolated cells and tissues perhaps via accumulated PG endoperoxides resulted by the inhibition of TXA2 synthase. Such an increase in PGI2 production by ozagrel was also observed in various experimental animals. We obtained the suggestion that, by the reduction of TXA2 production and increment of PGI2 production, ozagrel inhibits the spasms of basilar artery and the decreases in regional cerebral blood flow in dogs which received autologous blood into cisterna magna, and inhibits the decreases in motor function and regional cerebral blood flow, and the formation of infarcted area in the animals of cerebral ischemic treatment. It was also suggested that ozagrel inhibits leukotriene-, platelet-activating factor-, and antigen-induced bronchoconstriction in guinea-pigs and inhibits the induction of airway hyperresponsiveness by various stimuli in several species of animals by both mechanisms. The summarized results of ADME, toxicological, and clinical studies were also described.

Animals↗

Prediction of quality of life at long-term follow-up after Fontan operation by scoring risk factors.

Many factors will determine the quality of life at long-term follow-up after the Fontan operation. We tried to predict the long-term outcome of modified Fontan operation based on the combined assessment of various preoperative data. The preoperative condition was evaluated by a scoring system in which multilevel scores (from zero to 8 points) were given to a total of 14 morphological and physiological factors according to the contribution of each factor to mortality. The major factors were the association of the extracardiac total anomalous pulmonary venous connection, pulmonary arterial vascular resistance, mean pulmonary arterial pressure, PA index, ejection fraction of the main ventricle, and creatinine clearance. Points for each factor were determined according to surgical mortality, with zero points indicating no increased risk. The total score, i.e., the sum of the points for each item, in each patient was analyzed in relation to the patient's quality of life over a long-term follow-up, as evaluated by questionnaires. Twenty-six of 29 patients with scores of 5 or less showed normal or almost normal life long after the operation, whereas 5 of 10 with higher scores had restricted physical and daily activity. In conclusion, good preoperative condition predicts a good quality of life long after the Fontan operation. In addition, the concept of taking into account all possible risk factors as a comprehensive indicator may be useful in predicting long-term results.

Adolescent↗

Natural infection with attaching and effacing Escherichia coli (O15) in an adult cow.

A 19-month-old Holstein female manifested muco-hemorrhagic diarrhea. At necropsy, the colon contained a large amount of bloody material mixed with mucus and there was diffuse petechial hemorrhage on the mucosal surface. Histologic and electron microscopic examination of the colon revealed the characteristic lesion of attaching and effacing Escherichia coli (AEEC) infection. The organisms were associated with mucosal lesions and stained positively by an immunoperoxidase technique using antiserum to E. coli O group 15. Diarrhea caused by AEEC was recognized in this adult cow.

Animals↗

Pulmonary hypertension and antiphospholipid antibody in a patient with Sjögren's syndrome.

A 57-year-old female patient with Sjögren's syndrome was complicated with pulmonary hypertension (PH) and antiphospholipid antibody (aPL). She had a history of fetal losses, deep vein thrombosis and chronic thyroiditis. On admission, severe pulmonary hypertension, thrombocytopenia, lupus anticoagulant and a decreased level of protein C were found. Pulmonary artery perfusion scintigram revealed multiple defects. She died suddenly despite an intensive therapy. Intimal proliferation with angiomatoid lesions in small pulmonary arteries was observed by autopsy. Since a close relationship between PH and aPL in connective tissue disease is found, it is important to carefully analyze the antiphospholipid antibodies in patients with PH.

Antiphospholipid Syndrome↗

Differential malaria prevalence among villages of the Gidra in lowland Papua New Guinea.

Antibody titres against Plasmodium falciparum and P. vivax were examined using the indirect fluorescent antibody test (IFAT) for 183 Gidra-speaking adults and adolescents in four ecologically different villages of lowland Papua New Guinea. The findings highlight that 1) in Gidraland P. falciparum was more prevalent than P. vivax, 2) the proportion of antibody titres of 1:64 or higher markedly differed among the villages, ranging from 35.3% to 100% for males and from 31.6% to 100% for females, and 3) in the two villages with high prevalences, these were higher among males than females. The inter-village and sex differences can be largely explained by microenvironmental conditions and behavioural patterns of the population. The population-based analyses of this study intend to contribute to a better understanding of the prevalence of malaria in human-environment settings and thus to the planning of malaria prevention.

Adolescent↗

[Differential reactivities of three kinds of carbon dioxide absorbents with high concentration of sevoflurane].

The differential reactivities of three kinds of carbon dioxide absorbents, sodalime, Sodalime A and Baralyme with 5% sevoflurane were investigated in a closed system under administration of 5% carbon dioxide. The degradation products in the closed system were determined by gas chromatography and the temperature of the glass container which was filled with each carbon dioxide absorbent was monitored. The degradation products, P1, P3 and P5 were produced by every carbon dioxide absorbents even after one-hour circulation. Especially P3 and P5 were produced by Baralyme more than the others after two or four-hour circulation. The significant differences of the temperature among glass containers were not recognized. Previously we found that the reactivity of Sodalime A is the highest among the three kinds of carbon dioxide absorbents when low concentration of sevoflurane (2 or 3%) is used. Possible explanation for this result is that the increasing temperature of glass container filled with each carbon dioxide absorbent is different from each other, and Sodalime A is the highest. The reactivity was thought to depend on the temperature of glass container. However, with this high concentration of sevoflurane (5%), Baralyme has the highest reactivity. Baralyme contains higher proportion of KOH which has the highest reactivity with sevoflurane than the other constituents of carbon dioxide absorbents. The reactivity of sodalime, Sodalime A and Baralyme with 5% sevoflurane was thought to depend not on their temperature but on their chemical constitutions. These results suggested that the using high concentration sevoflurane with Baralyme should be reconsidered.

Absorption↗

Quantitative mapping of regional cerebral blood flow using iodine-123-IMP and SPECT.

UNLABELLED: A method was developed to calculate functional images of regional cerebral blood flow (rCBF) from a single scan using SPECT following intravenous 123I-N-isopropyl-p-iodoamphetamine (IMP) infusion. METHODS: A two-compartment model that includes two parameters of rCBF and regional distribution volume of IMP (Vd) was employed to correct for clearance of IMP from the brain. Using a given input function and a fixed Vd value (30 ml/ml according to an analysis on dynamic SPECT data), a unique value of rCBF was calculated for each pixel of the SPECT image according to the table-look-up procedure. This technique was applied to 15 human subjects, and the calculated rCBF values were compared with those measured by PET. RESULTS: A set of simulation studies demonstrated an optimal SPECT midscan time at 30 to 40 min postinjection of IMP, providing the minimal error sensitivity to the individual difference of the input function (rCBF values with an accuracy of +/- 10%). Another set of simulation suggested validity of fixing the Vd values, i.e., errors in calculated rCBF values were around +/- 7% for a change of Vd of +/- 10%. The measured rCBF values obtained from 15 human subjects were independent on the SPECT scan time. The calculated rCBF values also agreed well with those obtained by the nonlinear least-squares fitting analysis that were obtained from the dynamic SPECT scan and the frequent arterial blood sampling and measurement of lipophilic fraction for each sample (0.54 + 0.88x, r = 0.86), suggesting the validity of the simplified procedures in this method. CONCLUSION: These observations suggested the validity of this method as a clinical tool for quantitative measurement of rCBF.

Amphetamines↗

[Acute erythroblastic leukemia presenting as FAB M6 with surface marker positive for megakaryocytic and erythroid: report of a case].

A fifty five-year-old male presenting as FAB M6 had blasts that were positive both for erythroblastic and megakaryocytic surface makers, i.e., carbonic anhydrase I, CD36 and CD41. HLA-DR and cD71 were also positive. In a very small portion, CD33 and glycophorin A were also positive. By Giemsa staining, these blasts were relatively large and had basophilic cytoplasm. By electroscopic study, PPO was negative and showed ferritin particles, theta granules and iron containing mitochondria in cytoplasm. Chromosome analysis revealed major karyotypic abnormality (MAKA). After initial treatment with blood transfusion, prednisolone and exymetholone, CD41b increased in positive ratio. Trial of remission induction with BHAC-DMP failed and patient died in 5 months.

Antigens, CD↗