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Biomedical subjects

S Fujiwara

Publications and source records attributed to S Fujiwara.

At least 253 records · Page 14Linked to original sources

Identification of four metabolites of 3-(phenylamino)alanine, a constituent in L-tryptophan products implicated in eosinophilia-myalgia syndrome, in rats.

3-(Phenylamino)alanine (PAA), a contaminant found in L-tryptophan tablets, has been discussed as a possible cause of eosinophilia-myalgia syndrome (EMS). We administered PAA (100 mg/kg) by gastric gavage to Wistar rats to determine its distribution and metabolism. We developed a purification procedure, using Bond Elut SCX cartridges followed by high performance liquid chromatography (HPLC) in order to determine levels of PAA. The level of PAA in blood was 4.22 micrograms/ml at 5 h and urinary excretion was 21.7 micrograms for 5 h and 84.6 micrograms between 5 and 24 h. The amount of PAA in the contents of the large intestine at 5 h was 0.76 microgram, indicating poor transfer of PAA to the large intestine. However, the highest concentration of PAA was 12.3 micrograms/g in the brain, indicating the passage of PAA through the blood-brain barrier. In addition to detecting PAA in the blood and organs, we also detected four metabolites of PAA in urine. We used gas chromatography mass spectrometry to identify PAA in rat liver, as well as N-(hydroxyphenyl)glycine, N-phenylglycine, 3-(pheylamino)lactic acid, and 3-(hydroxyphenylamino)-lactic acid in rat urine. These results suggest that the degradation pathway of PAA is similar to that of phenylalanine.

Administration, Oral↗

Childhood bullous pemphigoid: immunohistochemical, immunoelectron microscopic, and western blot analysis.

The most reliable diagnostic criteria of childhood bullous pemphigoid (BP) have been the linear deposition of IgG and C3 at the basement membrane zone (BMZ) and the frequent presence of circulating IgG BMZ antibodies. To characterize further the immunologic features of childhood BP, we performed direct and indirect immunoelectron microscopy (IEM) and Western immunoblotting on specimens from a 3-month-old boy with BP who had immunofluorescence evidence of linear BMZ IgG and C3 deposition and circulating IgG BMZ antibody. By direct IEM, autoantibody deposits were seen in the upper portion of the lamina lucida and on the undersurface of basal keratinocytes. Indirect IEM showed that the binding sites of BP antibody were closely related to the intracellular attachment plaques of hemidesmosomes. By Western blotting, the patient's serum recognized 180 kd epidermal protein.

Autoantibodies↗

Antihypertensive and cardiovascular effects of a new potassium channel opener, TCV-295, in rats and dogs.

The antihypertensive and cardiovascular properties of a new potassium channel opener, TCV-295, were studied in rats and dogs. In conscious, spontaneously hypertensive rats (SHR), TCV-295 (0.03-1 mg/kg orally, p.o.) reduced blood pressure (BP) dose dependently with slow onset of action. The antihypertensive effects induced by TCV-295 lasted much longer than those of levcromakalim and nisoldipine, and the reflex tachycardia it evoked was less marked than that evoked by these drugs as compared at doses showing similar maximal hypotensive effects. Glibenclamide (30 mg/kg intravenously, i.v.) inhibited the TCV-295-induced BP decrease in anesthetized rats. In a 4-week chronic dosing study in SHR, TCV-295 (0.3 mg/kg/day p.o.) produced neither potentiation nor tolerance to its antihypertensive action and no rebound hypertension occurred when drug treatment was discontinued. In anesthetized normotensive dogs, TCV-295 (4.5 micrograms/kg/min i.v.) induced BP reductions accompanied by reductions in systemic vascular resistance. TCV-295 also reduced resistances of the coronary, vertebral, mesenteric, and renal vascular beds, and the most marked effect was observed in the coronary vasculature. Myocardial O2 consumption was reduced by TCV-295, possibly owing to afterload decrease. These results suggest that TCV-295 has a desirable profile for an antihypertensive agent.

Administration, Oral↗

Bullous pemphigoid in a 19-year-old woman. A case with unusual target antigens.

We report a 19-year-old woman with typical clinical histological and immunofluorescence features of bullous pemphigoid. By immunoblotting, the serum was shown to detect antigens at 240 and 138 kDa. Elevated serum IgE levels were present, and there was a marked peripheral blood eosinophilia. The degree of eosinophilia correlated with small changes in the severity of the skin lesions, and the IgE level showed correlation with marked changes in severity. Another unusual feature was an exacerbation of her disease at the time of her first menses after the onset of the bullous pemphigoid.

Adult↗

Flavanones with potent antibacterial activity against methicillin-resistant Staphylococcus aureus.

With the therapeutic concept of using the defensive ability of plants against microbial infections, phytoalexin, an antimicrobial phytochemical was studied for its ability to inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA). Extracts from Sophora exigua (Leguminosae) were fractionated by serial chromatography and the anti-MRSA activity of each fraction was determined by the agar-plate method. Among the active isolates, 5,7,2',6'-tetrahydroxy-6-isoprenyl-8-lavandulyl-4'-methox yflavanone (exiguaflavanone D) completely inhibited the growth of all the MRSA strains examined at the concentration of 1.56-6.25 micrograms mL-1, and 5, 2',6'-trihydroxy-8-lavandulyl-7-methoxy-flavanone (exiguaflavanone B) inhibited at a concentration of 50 micrograms mL-1. This former compound is expected to be a phytotherapeutic agent for MRSA infections as an alternative to conventional antibiotics with unwanted side-effects or the appearance of antibiotic-resistant bacteria.

Anti-Bacterial Agents↗

Intracranial aneurysms: diagnostic accuracy of three-dimensional, Fourier transform, time-of-flight MR angiography.

PURPOSE: To assess the accuracy of three-dimensional, Fourier transform, time-of-flight magnetic resonance (MR) angiography in the identification of intracranial aneurysms. MATERIALS AND METHODS: MR angiograms of 126 patients (59 male and 67 female patients, aged 12-77 years) with various intracranial vascular lesions were evaluated. Seventy-eight aneurysms, including 60 less than 5 mm in diameter, in 61 patients were depicted at conventional angiography. Eight projection images, as well as one axial collapsed MR angiogram obtained with a maximum-intensity projection algorithm, were used for evaluation. RESULTS: Sensitivity for the five observers ranged from 58% to 68% (mean, 63%). Higher sensitivity was achieved for anterior communicating and middle cerebral artery aneurysms, while that for internal carotid artery aneurysms was poor. Sensitivities for small and medium aneurysms ranged from 50% to 60% (mean, 56%) and from 77% to 94% (mean, 86%), respectively. CONCLUSION: MR angiography can depict intracranial aneurysms 5 mm or larger with good accuracy but is less useful for the identification of smaller aneurysms.

Algorithms↗

Intracranial vascular stenosis and occlusion: diagnostic accuracy of three-dimensional, Fourier transform, time-of-flight MR angiography.

PURPOSE: To assess the accuracy of three-dimensional, Fourier transform, time-of-flight magnetic resonance (MR) angiography in the detection of intracranial steno-occlusive diseases. MATERIALS AND METHODS: One hundred thirty-one patients (62 male and 69 female patients, aged 6-77 years [mean, 53 years 8 months]) underwent MR and conventional angiography for evaluation of possible intracranial vascular disease. A total of 502 arteries were assessed. Eight projections and a collapsed image postprocessed by means of a maximum-intensity projection algorithm were reviewed by five observers in a blinded manner, with conventional angiography as the standard. RESULTS: A total of 32 steno-occlusive lesions were available for review. Receiver operating characteristic analysis from the pooled data revealed overall sensitivities of 85% and 88% and specificities of 96% and 97% for the internal carotid artery and the middle cerebral artery, respectively. CONCLUSION: MR angiography is useful as the primary diagnostic tool for evaluating suspected intracranial steno-occlusive disease.

Algorithms↗

Case of cough syncope with seizure.

A rare case of cough syncope accompanied by seizure is presented. Interseizure electroencephalogram revealed in this 55-year-old man spikes and sharp waves over the bilateral temporal regions. Bronchodilators and antiepileptic medication effectively controlled cough syncope and seizure in this patient.

Bronchial Provocation Tests↗

A new bullous pemphigoid antigen.

Previously we reported a case of subepidermal blistering disease, which resembled bullous pemphigoid clinically. An immunoblot analysis revealed that the patient's serum reacted exclusively with a 450-kD epidermal polypeptide. The 450-kD antigen was also expressed in human keratinocytes and a human squamous carcinoma (HO 1-u-1 or A431) cell line. Using the patient's serum, cDNA clones in a bacteriophage lambda gt11 library derived from human foreskin keratinocytes were immune-screened. One positive clone was isolated from 2 million clones. Northern blot analysis showed that the inserted part of this clone hybridized with a more than 12-kb mRNA species derived from HO 1-u-1 cells. The deduced amino acid sequence had no homology with any other human component.

Autoantigens↗

Uric acid degrading enzymes, urate oxidase and allantoinase, are associated with different subcellular organelles in frog liver and kidney.

On the basis of differential and density gradient centrifugation studies, the site of the uric acid degrading enzymes, urate oxidase and allantoinase, in amphibia was previously assigned to the hepatic peroxisomes. Using specific antibodies against frog urate oxidase and allantoinase, we have undertaken an immunocytochemical study of the localization of these two proteins in frog liver and kidney, and demonstrate that whereas urate oxidase is present in peroxisomes, allantoinase is localized in mitochondria. Urate oxidase and allantoinase were detected by immunoblot analysis in both frog liver and kidney. The subcellular localization of these two enzymes was ascertained by Protein A-gold immunocytochemical staining of Lowicryl K4M-embedded tissue. Peroxisomes in frog liver parenchymal cells and kidney proximal tubular epithelium contained a semi-dense subcrystalloid core, which was found to be the exclusive site of urate oxidase localization. Allantoinase was detected within mitochondria, but not in peroxisomes of hepatocytes or proximal tubular epithelium. No allantoinase was detected in the mitochondria of nonhepatic parenchymal cells in liver and of the cells lining the distal convoluted tubules of the kidney. These results demonstrate that, unlike rat kidney peroxisomes which lack urate oxidase, peroxisomes of frog kidney contain this enzyme. Contrary to previous assumptions, these studies also clearly establish that urate oxidase and allantoinase, the first two enzymes involved in uric acid degradation, are localized in different subcellular organelles in frog liver and kidney.

Amidohydrolases↗

Acute purulent discitis with epidural abscess of the cervical spine in an adult--case report.

A 52-year-old male presented with acute purulent discitis and epidural abscess of the cervical spine manifesting as neck pain and slight fever, followed by sudden onset of quadriparesis. Magnetic resonance (MR) imaging showed a low-signal-intensity area in the C6/7 disc space and epidural space ventral to the spinal cord with peripheral enhancement. Surgical exploration using an anterior approach revealed local discitis and epidural abscess, but no osteomyelitis of the neighboring vertebral bodies. Six months after the decompressive procedure to treat the purulent disc and epidural abscess, he had achieved almost full recovery. Such lesions are rare in adults, but should be considered especially when painful spinal symptoms are associated with fever. Early and definitive diagnosis can be achieved by MR imaging with enhancement.

Brain Abscess↗

Effects of TCV-309, a novel PAF antagonist, on circulatory shock and hematological abnormality induced by endotoxin in dogs.

We investigated the effects of TCV-309, a novel platelet activating factor (PAF) antagonist, on circulatory dysfunction and hematological abnormalities in experimental canine endotoxin (ET) shock. ET caused biphasic hypotension with a decrease in cardiac output (CO), left ventricular systolic pressure (LVP) and its dp/dt(max). The first hypotensive phase occurred within 15 min, and the second phase between 90 and 180 min following the injection of ET. Pulmonary vascular resistance (PVR) abruptly increased at 15 min with a partial recovery, and was then sustained at twice the basal value throughout the experiment. TCV-309 attenuated the hypotension, the decrease in CO, LVP and its dp/dt(max), and the increase in PVR. TCV-309 had no significant effect on the increase in TPR. The decrease in plasma fibrinogen and the increase in hematocrit and plasma lactate were significantly attenuated by TCV-309. These data suggest that PAF may be a key mediator leading to shock in sepsis.

Animals↗

[Whole head measurement of auditory evoked magnetic field using a MR-linked helmet shaped MEG system].

Authors compared MR anatomy and magneto-encephalographic (MEG) functional methods in locating auditory cortex in 20 normal volunteers and 56 patients with intracranial structural lesions. Auditory evoked response was measured over the entire head, using a helmet shaped 64 channel MEG system. In each subject, three dimensional MR image was obtained with identical coordinate system of MEG. Best fit sphere to each subject's head was calculated from MRI data. Signal source of auditory evoked MEG was estimated using a two dipole model in the best fit sphere. Position and orientation of dipoles were superimposed on each subject's MRI. Both left and right dipolar patterns appeared about 100 ms after unilateral auditory stimuli (N100m) in 19 normal subjects and 47 patients. These dipolar patterns overlap each other across the midline. A two dipole model successfully localized bilateral N100m dipoles in the upper surface of superior temporal planes. N100m response was missing unilaterally in 1 normal subjects and 9 patients inspite of normal audiometry findings, suggesting sub-clinical auditory dysfunction. The MR-linked whole head MEG is a non-invasive tool to localize source of auditory evoked N100m response even in the case with intracranial structural lesions.

Acoustic Stimulation↗

Transdifferentiation of pigmented multipotent epithelium during morphallactic development of budding tunicates.

In the budding tunicate, Polyandrocarpa misakiensis, the atrial epithelium is the major formative tissue giving rise to the pharynx, digestive tract, brain and endostyle of a bud. We show here that this multipotent epithelium carries several differentiation markers that are lost in the process of bud development. In both adult animals and growing buds, the atrial epithelium contained orange-pigmented granules in the cytoplasm. In developing buds, on the other hand, the cells committed to organ primordia have lost the granules, taken a cuboidal shape and have a large nucleus with a prominent nucleolus, like undifferentiated cells. The atrial epithelium was also characterized by ALP expressed on the apical surface of the cell. During budding the enzyme activity disappeared from the atrial epithelium and reappeared in the primordial digestive tract. Immunohistochemical studies suggested strongly that during gut formation, ALP antigens has been switched from the epithelial isoform to the intestinal isoform. These results have shown that in P. misakiensis budding involves transdifferentiation of multipotent, but differentiated epithelium, confirming our previous results (Fujiwara and Kawamura, Dev. Growth Differ. 34:463-472, 1992).

Alkaline Phosphatase↗

[Locating the central sulcus using three dimensional image fusion system of helmet shaped whole head MEG and MRI].

We compared MR anatomy and magnetoencephalographic (MEG) functional methods in locating the central sulcus. In 20 normal volunteers and 58 patients with intracranial structural lesions, the short latency somatosensory evoked magnetic fields for median nerve and posterior tibial nerve stimuli were measured over the entire head, using a helmet shaped MEG system. The dipole positions estimated by a single current dipole model were projected onto the three dimensional MRI. In 94% of a total of 156 hemispheres, N20m dipole positions for median nerve stimuli coincided with the central sulcus defined by MR anatomical image only. For posterior tibial nerve stimuli, the P38m dipole positions were estimated as being near the medial end of the anatomical central sulcus. MRI and MEG are complementary in locating the central sulcus, even in cases of intracranial structural lesions.

Adolescent↗

Autoantibodies and immunoglobulins among atomic bomb survivors.

The purpose of this study was to determine if exposure to atomic bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody and immunoglobulin levels (IgG, IgM, IgA and IgE) were measured among 2,061 individuals exposed to atomic bomb radiation in Hiroshima and Nagasaki whose estimated doses ranged from 0 to 5.6 Gy. The prevalence and titers of rheumatoid factor were found to be increased in the individuals exposed to higher radiation doses. The IgA level in females and the IgM level in both sexes increased as radiation dose increased, although the effects of radiation exposure were not large. No effect of radiation was found on the prevalence of antinuclear antibody, antithyroglobulin antibody and anti-thyroid-microsomal antibody or on the levels of IgG and IgE.

Adult↗