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Biomedical subjects

T Fujiwara

Publications and source records attributed to T Fujiwara.

At least 667 records · Page 37Linked to original sources
PubMed1994

Assessment of dopamine metabolism in brain of patients with dementia by means of 18F-fluorodopa and PET.

By means of positron emission tomography (PET) and 18F-fluorodopa (FDOPA), a study was initiated to analyze the cerebral dopamine (DA) metabolism of 32 subjects including those with AD/SDAT and vascular dementia (VD, multi-infarct type). A semiautomated irregular ROI drawing routine to identify the striatum was developed that interactively defined the PET threshold pixels referring to the count histograms and location of the corresponding pixels. A comparative study by five examiners showed significant improvement in the area size definition and count linearity particularly for low contrast objects. The graphical plot was employed to calculate the FDOPA influx rate (Ki) for the ROI data with cerebellar radioactivity as an input function. The striatal Ki value was found to be relatively stable and did not show signs of a significant age-related change. The vascular patients had smaller Ki to the striatum than the aged control. Although the mean Ki of AD/SDAT was almost compatible with that of age-matched normals, their Ki was more scattered with higher and lower Ki cases. The multiple regression analysis revealed that the Ki could be predicted by age and the mini-mental state (MMS) performance (r2 = 0.590, p < 0.01 for AD/SDAT, r2 = 0.401, and p < 0.05 for VD). MMS was found to be a more dominant factor than age. We conclude that dopamine metabolism became disturbed as dementia became progressively severe.

Aged↗
PubMed1994

Abnormal distribution of nerve terminals in infantile hypertrophic pyloric stenosis.

Smooth muscle biopsy specimens obtained from nine infants with infantile hypertrophic pyloric stenosis (IHPS) and from three controls were studied immunohistochemically with respect to the distribution of nerve terminals and neurofilaments. To label nerve terminals and neurofilaments, monoclonal antibodies (MAb) 171B5 and 2F11 were used, respectively. In all specimens of the control group, nerve terminals were numerous in both the myenteric plexus and the muscle layer. There were abundant neurofilaments in the myenteric plexus and a moderate number in the muscle layer. In all specimens of the IHPS group, the density of nerve terminals and neurofilaments was reduced in the muscle layer. In the myenteric plexus, there was no such reduction. The results indicate poor neuronal innervation of the muscle layer in the pylorus of infants with IHPS. This poor innervation may be related to the pathogenesis of pyloric stenosis and hypertrophy.

Antibodies, Monoclonal↗
PubMed1994

Metabolic disturbances in exo-focal brain areas after cortical stroke studied by positron emission tomography.

We have reported that exo-focal delayed neuronal damage was observed in the ipsilateral thalamus and the substantia nigra of the rat brain after occlusion of the middle cerebral artery (MCA). To determine if that phenomenon also occurs in humans, we measured cerebral metabolic rates for glucose (CMRGlc) in the remote brain areas at a chronic stage after cortical infarction using 2-[18F]fluoro-2-deoxy-D-glucose and position emission tomography (PET). The subjects studied were 11 patients who were affected by unilateral cerebral infarction in the cortex supplied by MCA. There were significant decreases of CMRGlc as compared with control values (p < 0.01), not only in the cerebral cortex directly damaged by the ischemic insult, but also in the ipsilateral thalamus and in the contralateral cerebellum, areas in which no lesions had been detected by MRI or CT scan. The present study indicates that different mechanisms may be responsible for multi-focal metabolic disturbances in the remote areas after stroke. The reduction of CMRGlc in the contralateral cerebellum may be explained by the crossed cerebellar diaschisis theory and in the ipsilateral thalamus as being due to retrograde degeneration associated with the infarcted cortex. We suggest that these multi-focal brain dysfunctions caused by neuronal network disturbances may exacerbate clinical symptoms at a chronic stage of stroke.

Adult↗
PubMed1994

Maturational changes in superoxide anion production of rabbit alveolar macrophages.

We investigated the effect of maturation on the superoxide anion production of rabbit alveolar macrophages by endothelin-1, N-formyl-methionyl-leucyl-phenylalanine, and phorbol 12-myristate 13-acetate. The O2- production by phorbol 12-myristate 13-acetate in young (0.2-0.3 kg) rabbits was as high as that in adult (3.0-3.5 kg) rabbits. However, when alveolar macrophages were stimulated by N-formyl-methionyl-leucyl-phenylalanine or preincubated with endothelin-1 before phorbol 12-myristate 13-acetate stimulation, O2- production of young rabbits was relatively weak compared to adult rabbits. The present data indicate that the ability of O2- production is sufficiently developed with a chemotactic peptide which directly stimulates protein kinase C.

Aging↗
PubMed1994

Meconium-induced lung injury mediated by activation of alveolar macrophages.

To clarify the mechanism of meconium-induced cellular injury, we examined the effect of meconium on the alveolar macrophages (AM) and bronchial epithelial cells (AK-D). Meconium obtained from healthy newborns was added to culture medium of AM and/or AK-D, which were cultured for 1 hour. Superoxide anion production of AM and the expression of intercellular adhesion molecule-1 (ICAM-1) on AK-D stimulated by meconium or oxygen radicals were determined. As a result, superoxide anion production of AM significantly increased when AM was cultured with meconium. Expression of ICAM-1 on AK-D appeared when AK-D was stimulated by hydroxyl radical but did not when AK-D was cultured with meconium. These results suggest that meconium-induced lung injury may occur through an activation of alveolar macrophages and the macrophage-epithelial cell axis may be important for the pathogenesis of meconium aspiration syndrome.

Animals↗
PubMed1994

Primary cerebellar yolk sac tumor: case report.

A rare case of cerebellar yolk sac tumor is described. A 4-year-old boy was admitted for the treatment of a cerebellar tumor and, following total removal of the tumor, he was treated with combination chemotherapy consisting of cisplatin, vinblastine, and bleomycin. He died 18 months after the primary diagnosis due to tumor recurrence. Serum alpha-fetoprotein level was well correlated with the clinical course and the amount of the tumor mass in neuroimaging.

Cerebellar Neoplasms↗
PubMed1994

Quantitation of [11C]diprenorphine cerebral kinetics in man acquired by PET using presaturation, pulse-chase and tracer-only protocols.

The quantitation of regional cerebral in vivo opioid receptor rate constants using [11C]diprenorphine and positron emission tomography (PET) using 3 types of protocol (presaturation, pulse-chase naloxone displacement and tracer-only protocols) together with measurements of regional cerebral blood flow is described in normal volunteers. Arterial blood was sampled continuously for radioactivity and was corrected for metabolites and plasma/blood partition of radioactivity to provide a continuous plasma input function. A compartmental model involving 3 tissue compartments was used to describe the regional cerebral pharmacokinetics of the tracer. The compartments comprised: (1) free plus rapidly exchanging non-specifically bound ligand, (2) specifically bound, naloxone displaceable ligand, and (3) a kinetically distinguishable non-specifically bound pool. Regional estimates of fractional rate constants relating to specific binding were obtained using naloxone in a pulse-chase design of tracer displacement. Less precise estimates of these rate constraints were obtained from single-tracer-only studies, but when binding was expressed as the tissue total volume of distribution relative to plasma there was good correlation with regional values obtained from pulse-chase studies performed in the same individuals. The application of these protocols to the measurement of indices of regional-specific opioid receptor binding in the human brain is discussed.

Adult↗
PubMed1994

A molecular dynamics study of branched alpha-cyclodextrin.

A branched alpha-cyclodextrin is a derivative of an alpha-cyclodextrin with a branch consisting of an extra glucose unit. Its water solubility is considerably higher than that of the unbranched one. We have studied the high solubility of the molecule in aqueous solution by molecular dynamics simulations. Trajectories of the molecule at 293 K were calculated using GROMOS programs in three different environments, i.e., in vacuo, in the crystalline state, and in aqueous solution. A simulation in vacuo was carried out to explore stable conformations of the molecule in the isolated system. The quality of the simulations were examined by comparing the X-ray and the simulated crystal structures. The results of the simulations show three remarkable structural features of the molecule: self-inclusion with its branched portion, twist-boat conformation of a glucose ring, and wobbling of its macrocycle. Among these, the last feature is closely related to the water solubility of the molecule. The solubility of cyclodextrin appears to be mainly governed by its intramolecular interglucose hydrogen bonds, which inhibit hydration by solvent water molecules. The results of our simulations indicate that the capability to form hydrogen bonds in branched alpha-cyclodextrin decreased as the macrocycle of the molecule lost its regular circular shape. Such wobbling of the macrocycle was observed on a relatively short time scale (several picoseconds). An extra glucose unit introduced to alpha-cyclodextrin may cause the improved water solubility of the molecule through the greater wobbling motion of its macrocycle.

Carbohydrate Conformation↗
PubMed1994

Magnetic resonance imaging of heterotaxia in infants.

OBJECTIVES: This study assessed the usefulness and safety of magnetic resonance imaging (MRI) for systematically diagnosing heterotaxia in infants. BACKGROUND: Although it is important to diagnose and treat infants with heterotaxia, which is associated with viscerobronchial cardiovascular anomalies, systematic diagnosis of these anomalies by a single imaging technique is difficult. METHODS: Twenty patients with heterotaxia were evaluated. The infants ranged in age from 21 days to 12 months (average 5.2 months, average body weight 4.3 kg). Electrocardiographically gated MRI was performed by spin echo imaging techniques operating at 0.5 tesla. RESULTS: In all 20 patients, MRI results were sufficient to evaluate these anomalies without serious complications. In 17 patients, neither a spleen nor splenules were detected, but in 3 patients, a polymorphous spleen was visualized. In all 20 patients, bronchial anatomies were clearly visualized (bilateral eparterial bronchi in 14 patients, bilateral hyparterial bronchi in 2 and normal bronchial patterns in 4). Additionally, in a comparison of 149 observations of cardiovascular anatomy by MRI with those by angiography, discrepancies were found in only 10 observations (6.7%). CONCLUSIONS: Magnetic resonance imaging was found to be safe and very useful for the systematic diagnosis of heterotaxia in infants.

Abnormalities, Multiple↗
PubMed1994

Generation of hydrogen peroxide by varicella-zoster virus-stimulated polymorphonuclear leukocytes.

BACKGROUND: In varicella-zoster virus (VZV) infections, the initial response in cutaneous lesions is predominantly polymorphonuclear leukocytes (PMN). However, interaction of VZV and PMN has not yet been fully defined. OBJECTIVES: To explore the potential role of PMN in VZV infections, we investigated the ability of PMN to generate hydrogen peroxide (H(2)O(2)) after stimulation with VZV antigen. STUDY DESIGN: H(2)O(2), one of the reactive oxygen species, was measured by cytofluorography after PMN were incubated with varicella-zoster virus (VZV) antigen in the presence of seropositive or seronegative serum. RESULTS: H(2)O(2) was detectable in unseparated PMN obtained from seropositive children and adults, while unseparated PMN of seronegative donors were not capable of generating H(2)O(2). Separated PMN obtained from either seropositive or seronegative donors were capable of generating H(2)O(2) in the presence of seropositive serum. However, H(2)O(2) was not detectable in separated PMN of seropositive donors in the presence of seronegative serum. The of H(2)O(2) generation did not correlate with concentrations of serum antibodies to VZV. CONCLUSIONS: VZV antigen-antibody complexes might induce H(2)O(2) generation by PMN.

Journal Article↗
PubMed1994

Effects of patent ductus arteriosus on left ventricular output and organ blood flows in preterm infants with respiratory distress syndrome treated with surfactant.

Thirty preterm infants (birth weight < 1500 gm) treated with Surfactant TA for the respiratory distress syndrome, who had no complicating clinical problems other than ductal patency, were studied by serial Doppler flow examinations to determine the effects of early left-to-right shunt through the patent ductus arteriosus on the left ventricular output and organ blood flows. Doppler flow variables in 15 infants with a hemodynamically significant patent ductus arteriosus (hsPDA) were compared with those in 15 subjects without hsPDA matched for age, body weight, and gestational age. Infants with hsPDA had significantly higher left ventricular output and significantly lower blood flow volume in the abdominal aorta, and lower temporal mean blood flow velocities, with concomitant increases in the relative vascular resistance in the celiac artery, superior mesenteric artery, and renal artery. Pulsatility indexes of these vessels and the anterior cerebral artery were significantly higher in the hsPDA group, but the temporal mean blood flow velocities in the anterior cerebral artery and its vascular resistance were not significantly different between the two groups. After closure of the patent ductus arterious was achieved with mefenamic acid therapy, alterations in Doppler flow variables in the hsPDA group reverted to the levels seen in the group without hsPDA. These results suggest that despite large left-to-right ductal shunting, the heart of the preterm infant is capable of mounting a compensatory increase of cardiac output sufficient to maintain unchanged cerebral blood flow, but is unable to maintain postductal organ blood flows because of decreased perfusion pressure (ductal steal) and localized increase in vascular resistance.

Blood Flow Velocity↗
PubMed1994

Changes in central opioid receptor binding in relation to inflammation and pain in patients with rheumatoid arthritis.

A group of four patients with RA were examined to test the hypothesis that there is a change in the endogenous opioid system in the brain during inflammatory pain. Regional cerebral opioid receptor binding was quantified using the opioid receptor antagonist [11C] diprenorphine and positron emission tomography (PET). In the four patients studied in and out of pain, significant increases in [11C]diprenorphine binding were seen in association with a reduction in pain. Increases were seen in most of the areas of the brain that were sampled apart from the occipital cortex. Significant region-specific increases over and above the more generalized changes were also seen in the frontal, cingulate and temporal cortices in addition to the straight gyrus. These findings are consistent with the hypothesis that there are substantial increases in occupancy by endogenous opioid peptides during inflammatory pain.

Arthritis, Rheumatoid↗
PubMed1994

Gene therapeutics and gene therapy for cancer.

Recent advances in molecular biology have opened new avenues of basic genetic engineering technology and have made possible the application of this technology in clinical human gene therapy. Replication-defective viral vectors and biocompatible materials, eg, liposomes, have been developed as vehicles to introduce potentially therapeutic genes into mammalian cells. Over the past 2 years, this technology has increased the possibilities for therapy in numerous genetic diseases. Approaches at the molecular level have also demonstrated that one of the mechanisms of human cancer development is overexpression of dominant oncogenes, expression of mutant oncogenes, or specific chromosomal deletions or mutations that induce inactivation of tumor-suppressor activity. This concept suggests that the introduction of antisense oncogenes and wild-type tumor-suppressor genes, eg, p53, could halt or reverse these mechanisms, thus having a therapeutic effect in cancer. Moreover, evidence that the immune system is capable of eliminating tumor cells in numerous animal models has suggested gene therapy approaches for the delivery of cytokines, which promote the activation of cytotoxic immune responses against the malignant tissue. The efficacy of these gene therapy protocols is now being evaluated in both animal model systems and clinical trials. This article reviews recent highlights in this rapidly evolving field.

Cytokines↗