Biomedical subjects
Publications and source records attributed to J Okada.
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After inhalation of 15% CO2, immunoreactions to glutamate and glutamic acid decarboxylase were found in some c-Fos or c-Jun-labeled neurons distributed in the reticular region just dorsal to the pyramidal tract in the rostroventromedial medulla (parapyramidal RVMM). This region forms vertically the narrow strip between the nucleus raphe pallidus and nucleus parapyramidalis superficialis, and extends rostrocaudally from the level just ahead of the inferior olivary complex to the level just behind the nucleus of the trapezoid body. When we placed lesions with kainate in the parapyramidal RVMM, hyperpneic and tachypneic responses to brief inhalation of 15% CO2 were completely abolished, and the eupneic rhythm changed into the gasping rhythm. This study suggests that the parapyramidal RVMM consists of neuronal substrates that subserve as the respiratory rhythm modulator.
We have applied the artificial neural network method to estimate the N20-P20 dipole from scalp SEP potentials, and have investigated the rotation of the dipole moment caused by the compression effect of a brain tumor (para-Rolandic tumor) adjacent to the central sulcus. The variation of the frontal P20 potential was demonstrated by the rotation of the N20-P20 dipole moment in 8 cases of para-Rolandic tumor. By estimation of the rotation of the dipole moment, it may be possible to obtain preoperative information regarding the relation between the central sulcus and the tumor.
We previously reported that the VP7 gene from simian rotavirus SA11 with G-serotype 3(G3-VP7 gene) was preferentially selected in the genetic background of SA11 compared with the G1- or G2-VP7 gene. In the present study, selection of the G4-VP7 gene in competition with G1-, G2- or G3-VP7 gene in the SA11 background was analyzed through mixed infection experiments using SA11 and SA11-human rotavirus single-VP7 gene-substitution reassortants with G-serotypes 1, 2, and 4 (G1-, G2- and G4-reassortant). In virus clones from coinfection of SA11 and G4-reassortant, the frequency of G4 virus decreased to 7% at the 3rd passage and the G4 virus disappeared at the 10th passage, whereas the majority of the clones possessed G3 specificity. However, the predominance of either of the viruses coinfected was not observed in the mixed infection with G4-reassortant and G1- or G2-reassortant. Although growth kinetics of SA11 and G4-reassortant was similar, G4-reassortant showed significantly smaller plaque size than SA11, G1- and G2-reassortant did. These results indicated that the G3-VP7 gene from SA11 might be preferentially selected in the SA11 genetic background compared with the G4-VP7 gene, and suggested that the introduction of a single G4-VP7 gene may affect growth characteristics of recipient virus SA11. These results together with our previous findings suggested the significance of genetic compatibility between recipient viral genes and foreign VP7 gene in the development of multivalent reassortant rotavirus vaccines.
We experienced a SLE patient with TSS after delivery. A 32-year-old SLE patient was transferred to our division due to fever, diarrhea, erosive rash, pericardial effusion, myalgia, low blood pressure, thrombocytopenia and hypoproteinemia which appeared two days after transvaginal delivery. At the time of admission, we considered these symptoms as the exacerbation of SLE, and treatment with high doses of steroid was started. It was when TSST-1-producing-MRSA was cultured from the vagina and uterus that TSS was suspected. 2 g/day of vancomycin was administered and her symptoms improved. As observed in this case, it is important to consider TSS as one of the complications seen with SLE patients after delivery.
Issues discussed by TK Working Group of the JPMA for the implementation of ICH guideline for toxicokinetics (TK) are summarized. 1) A unique management system may be needed for toxicokinetic studies, when TK measurements are conducted in a center for pharmacokinetics and metabolism studies, i.e. in a separate location or by an independent organization from those for toxicity studies. 2) TK measurement should be conducted in compliance with the protocols and validated SOPs for analytical methods. 3) Every time when study conditions in toxicity studies and/or TK measurement are changed, the analytical method should be more or less revalidated. The present paper will discuss some practical issues to be involved in such situations, and possible countermeasures for them.
The hepatocyte growth factor (HGF) regulates growth, motility, and morphogenesis of epithelial and endothelial cells. It has been reported that serum level of HGF was elevated in patients with having fulminant hepatitis. In inflammatory myopathies (IM), muscle cells are damaged by the inflammatory process and subsequently regenerated. HGF may be involved in the regeneration process of muscle cells in IM. We examined serum HGF was measured by ELISA from 13 patients with having polymyositis (PM), 18 patients with having dermatomyositis (DM), 3 patients with amyopathic dermatomyositis (ADM) and 14 normal individuals. The muscle of IM patients was examined by immunofluorescence staining using a monoclonal anti-HGF antibody. The serum HGF level was significantly higher in IM patients (0.63 +/- 0.11 (p = 0.028) in PM, 0.58 +/- 0.07 (p = 0.023) in DM) than in normal controls (0.26 +/- 0.01 ng/ml). However, there was no relationship between the serum HGF level and hepatic enzyme level in IM. The levels of serum HGF were significantly higher in active disease (1.05 +/- 0.26 ng/ml) than in inactive disease (0.29 +/- 0.03 ng/ml) (p = 0.044). The serum HGF levels (0.77 +/- 0.12 ng/ ml) were significantly higher in IM patients with pulmonary fibrosis than in those (0.42 +/- 0.04 ng/ml) without pulmonary fibrosis (p = 0.049). There was a positive relationship between serum HGF levels and the presence of opaque fiber and/or regeneration/degeneration fiber in biopsied muscles. HGF was detected in muscles from IM patients by immunofluorescence. Serum HGF levels are elevated in IM and correlated with disease activity and complication of interstitial pneumonia.
OBJECTIVE: To investigate risk factors for Pneumocystis carinii pneumonia (PCP) in patients with systemic lupus erythematosus (SLE) and polymyositis/dermatomyositis (PM/DM). METHODS: The subjects were 75 patients hospitalized because of SLE or PM/DM who were administered corticosteroids 40 mg/day or above as prednisolone. The relationship between clinical symptoms of SLE and PM/DM and the occurrence of PCP was evaluated. RESULTS: Seven patients (9.3%) developed PCP and 3 died. Interstitial pulmonary fibrosis was observed in all 7 patients who developed PCP, and its incidence was significantly higher (p < 0.001) than in those who did not develop PCP (6/68). The incidence of PCP in patients with SLE was 1.7%, but that of patients with PM/DM was 37.5%. The peripheral blood lymphocyte count was 1052.7/microliters in patients who developed PCP, which was significantly lower (p < 0.01) than 1841.6/microliters in patients who did not develop PCP. CONCLUSION: A low peripheral lymphocyte count and interstitial pulmonary fibrosis were considered risk factors for PCP in patients administered corticosteroids for SLE or PM/DM.
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Vagal motor neurons in the rat dorsal motor nucleus of the vagus (DMN) are known to receive direct synaptic input from enkephalin-containing terminals. We examined 1) whether the vagal motor neurons within the nucleus ambiguus (NA) also received monosynaptic input from enkephalin-immunoreactive terminals and 2), if so, whether their ultrastructural relations differed from those in the DMN. In both regions, terminals containing Leu5-enkephalin-like immunoreactivity (LE-LI) were examined in relation to motor neurons identified by retrograde transport of wheat germ-agglutinated horseradish peroxidase (WGA-HRP) applied to the cut end of the cervical vagus nerve in single sections of the medulla oblongata of adult rats. By light microscopy, the most significant overlap between varicose processes with LE-LI and WGA-HRP-containing neurons was seen in the rostral compact portion of the NA and the DMN at the level of the obex. Thus, only these regions were examined by electron microscopy. The most distinguishing ultrastructural feature of WGA-HRP-labeled neurons in the NA compared to the DMN was their higher incidence of nonsynaptic appositions with other neurons. In both the NA and the DMN, terminals with LE-LI formed primarily symmetric synapses on smaller (presumably distal) dendrites; many of these dendrites, as well as most target perikarya, contained WGA-HRP. Additionally, in the compact portion of the NA compared to the DMN 1) multiple LE-labeled terminals more frequently contacted single perikarya or dendrites and 2) single terminals with LE-LI more commonly showed two contacts or active zones and contained more abundant LE-immunoreactive large (80-100 nm) dense-core vesicles (dcvs). In contrast to small (40-50 nm), clear vesicles, which were usually aggregated near active zones, the immunoreactive dcvs were usually located near glial processes distal to these zones. These results indicate that enkephalin immunoreactivity is intensely localized to dcvs within terminals that may have direct inhibitory (symmetric synapses) actions on vagal motor neurons in both the compact portion of the NA and the DMN. Moreover, because numbers of dcvs and active zones have been equated with synaptic strength, our findings suggest enhanced potencies of enkephalin-immunoreactive terminals in the compact portion of the NA. Our findings support a prominent role for enkephalin in the coordinated activity of esophageal motor neurons located in the compact portion of the NA.
We studied and characterized anti-bovine beta 2-glycoprotein I antibodies (aB beta 2-GPI) in sera from patients with antiphospholipid syndrome (APS) by ELISA. Bovine beta 2-glycoprotein I (beta 2-GPI) was purified by heparin affinity and DEAE ion-exchange chromatography, and identified on immunoblots using a monoclonal antibody against human beta 2-GPI and by amino acid sequence analysis. aB beta 2-GPI levels in the sera from 36 APS patients were measured by ELISA using purified bovine beta 2-GPI as an antigen. The mean +/- standard deviation level of aB beta 2-GPI was 17.4 +/- 22.0 units in the 58% of APS patients who were positive. There was a significant correlation (P = 0.003) between aB beta 2-GPI and anticardiolipin antibody (aCL) levels. aB beta 2-GPI from the sera of patients with APS was inhibited by bovine beta 2-GPI itself. Purified IgG from the sera of patients with APS showed that bovine beta 2-GPI was capable of acting as a cofactor for aCL. Purified bovine beta 2-GPI was useful antigen for conventional ELISA. aB beta 2-GPI may contribute to the further development of aCL analysis and to the understanding of the pathogenesis of APS.
In a patient with cerebrotendinous xanthomatosis, a rare familial sterol storage disease, increased uptake of gallium-67 was observed in the tendon xanthomas. This is considered to have resulted from the tumour-like proliferation of histiocytic cells in the xanthomas. Abnormalities in the white matter of the cerebellum and the brain stem observed by X-ray computed tomography and magnetic resonance imaging were not detected by 67Ga scintigraphy, possibly due to the small size of the CNS lesions.
The physical characteristics of polymerized liposomes for potential use as an oral drug delivery system were examined in vitro. The trap efficiency in monomeric liposomes composed of 1,2-di (2,4-octadecadienoyl) phosphatidylcholine was increased from 3% for original multilamellar vesicles to 35% for freeze-thaw treated liposomes. Polymerized liposomes with azobis (isobutyronitrile) and azobis (2-amidinopropane) hydrochloride as radical initiators showed complete stability against solubilization by Triton X-100, a detergent chosen to mimic bile salts. Release rates of 14C-BSA and 14C-sucrose in media simulating the gastro-intestinal fluids was 50% less than from regular liposomes composed of hydrogenated egg phosphatidylcholine mixed with cholesterol (molar ratio 1:1), which can be regarded as one of the most stable types of regular liposomes. It was estimated that, when administered orally, polymerized liposomes can reach the intestine while maintaining their vesicle structure and keeping at least 75% of their original content.
A case of Raynaud's phenomenon, was complicated with autoimmune hepatitis (AIH) during the clinical course, and subsequently with gangrene of the fingertips caused by CRST syndrome (calcinosis cutis, Raynaud's phenomenon, sclerodactyly and telangiectasia). The presence of anticentromere antibodies is rare in AIH; to date, there has been only one report of a combination of AIH and CRST syndrome. This combination of the two diseases has been identified only in Japan.
It has not been clarified that the anti-platelet antibodies are related to thrombocytopenia in systemic lupus erythematosus (SLE). We evaluated the presence of anti-platelet antibodies in sera from patients with SLE using immunoblot analysis. In this study, 19 of 65 cases (29.2%) in SLE had anti-platelet antibodies in their sera, whereas no anti-platelet antibodies were detected in 16 cases of rheumatoid arthritis, 16 cases of progressive systemic sclerosis, 2 cases of polymyositis-dermatomyositis and 10 healthy controls. Six bands of 200 kDa, 140 kDa, 120 kDa, 95 kDa, 80 kDa and 65 kDa molecular weight were detected using immunoblot analysis. The platelet antibodies to 95 kDa and 80 kDa proteins were frequently detected in 12.3% and 16.9% respectively of SLE. These 2 antibodies were absorbed with the platelet pellet derived from healthy person. Therefore, it was suggested that the antibodies to 90 kDa and 80 kDa platelet antigens were specific to platelet membrane protein. Although we could not find any correlation between clinical and laboratory manifestations of SLE and these platelet antibodies, these antiplatelet antibodies were specifically detected in sera from patients with SLE by immunoblot analysis.
This case involves a 41-year-old woman with SLE. The patient began having symptoms of arthralgia in 1978 and developed fever, pleuritis and lupus psychosis in 1986. Laboratory exams showed positive antinuclear-antibody, LE-cell phenomenon, hypocomplementemia and lupus anticoagulant. Echo cardiography demonstrated mitral regurgitation and stenosis. She was treated with 50 mg of prednisolone and these manifestations subsided. In 1989, she developed dyspnea on exertion and echo cardiography revealed severe mitral stenosis. Pulmonary infarction was detected by MAA lung scintigraphy. At this time, she was diagnosed as SLE associated with antiphospholipid syndrome (APS). A mitral valvular replacement operation was performed in 1991. Pathological studies of mitral valve demonstrated Libman Sacks endocarditis. APS is known occasionally to complicate with left-sided valvular diseases, mitral stenosis is quite rare in both SLE and APS. This patient reveals a rare case of SLE associated with APS and mitral stenosis. It is suggested that this patient developed mitral stenosis with Libman Sacks endocarditis, associated with the presence of antibody against phospholipids.
Thallium-201 (201Tl) SPECT was performed 48 times in 26 patients to clarify its usefulness in the evaluation of malignancy and viability of brain tumors. The early counts ratio (ER) and delayed counts ratio (DR) of a lesion compared with normal brain were obtained 10-15 minutes and 3 hours, respectively, after intravenous administration of 185 MBq of 201Tl chloride. Untreated high grade malignant tumors and recurrent tumors did not always show high ER and DR, and they were widely distributed. High grade malignant tumors that showed low ER and DR were not well enhanced on CT or MRI. In low grade malignant tumors, such as pituitary adenoma which was well enhanced on CT, ER and DR were as high as in high grade malignant tumor. Whether a tumor recurred within three months after radiotherapy or not was retrospectively predicted at accuracy rates of 93.8% and 87.5% with cut-off points of 4.0 for ER and 3.5 for DR. Cerebral radiation necrosis showed ring-like increased uptake of 201Tl in proportion to the progress of necrosis and intensity of enhancement on MRI. In conclusion 201Tl SPECT is considered to be less useful for lesions that are well enhanced on CT, because they show high uptake of 201Tl regardless of their malignancy and viability. On the other hand, in tumors that are not well enhanced on CT. 201Tl shows good accumulation in viable and high grade malignant lesions. 201Tl SPECT should be performed in such cases.