[The relationship between disability status and scores of comprehensive geriatric assessment].
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Biomedical subjects
Publications and source records attributed to M Iwata.
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Therapeutic use of radionuclides includes 131I for thyroid cancer and hyperthyroid Graves' disease, 89SrCl3 for metastatic bone tumors, 131I-MIBG for malignant pheochromocytoma and neuroblastoma, and radioimmunotherapies. 131I is concentrated in 60-70% of metastases from differentiated thyroid cancer following total thyroidectomy. Radioiodine uptake in metastatic lesions is greater in younger patients than in older ones. Hypothyroidism is often mild or even absent in patients with a large amount of tumor tissue, indicating that thyroid hormones produced by highly differentiated tumors compensate partially or even completely for hypothyroidism following total thyroidectomy. Adequate uptake of 131I has been reported to be associated with significant reduction in the size and number of metastases, and with lower recurrence and higher survival rates. Other favorable factors for longer survival are younger age, well-differentiated histological type, small disease extent, and early discovery of metastases. Older patients with extensive metastases and/or bulky tumor masses in the bone have a poor prognosis. Therefore, it is important to discover metastases as early as possible, when patients are still young. Long-term follow-up with periodic thyroglobulin measurements and imaging studies is strongly recommended. In Japan, 131I treatment for Graves' disease is performed only in selected patients in whom antithyroid drugs cannot be used because of side effects or not effective, considering the high prevalence of permanent hypothyroidism. 89SrCl3 is useful for reducing pain due to bone metastases of malignant tumors. 131I-MIBG therapy is effective for improvement of QOL in some patients with metastatic malignant pheochromocytoma. Radioimmuno-therapy using anti-CD20 has been used successfully in clinical application in patients with malignant B cell lymphoma.
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We reported a patient with acquired immunodeficiency syndrome (AIDS)-associated progressive multifocal leukoencephalopathy (AIDS-PML), whose condition improved after highly active anti-retroviral therapy (HAART). A 70-year-old man was admitted to our hospital because of worsening left hemiplegia and disturbance of consciousness. During the past 30 years, he frequently traveled to the United States and southeast Asia. On neurological examination, he was somnolent and left hemiplegia with severe rigospasticity was present. The deep tendon reflexes showed hyper-reflexes with extensor plantar responses. Laboratory studies showed pancytopenia and positive HIV-1 antibodies. The CD4 cell count was 38/mm3 and his HIV viral RNA load in the blood was 9,500 copies/ml. T2-weighted magnetic resonance imaging (MRI) of the brain revealed asymmetrical high intensity white matter lesions in the right fronto-parietal, and left frontal regions and in the cerebellar hemisphere. The cerebrospinal fluid (CSF) protein elevated to 91 mg/dl with a normal cell count. The diagnosis of PML was confirmed by the detection of JC virus DNA in the CSF using a nested polymerase chain reaction assay. Three weeks after starting HAART with zidovudine, lamivudine, and indinavir, he was able to respond to simple commands. Two months later, the HIV viral RNA load decreased to less than 400 copies/mm3, and no JC virus DNA was detected in the CSF, with an increase of the CD4 cell count to 285/mm3 in the blood. A follow-up MRI of the brain showed a reduction in the cerebellar and cerebral white matter lesions. The recovering immune function by decreasing of the HIV load after HAART might suppress JC virus replication. It was suggested that HAART would become a beneficial treatment for patients with AIDS-PML.
The raw material of thiamine hydrochloride solution was examined for preparation of the "Thiamine Hydrochloride Solution Reference Standard (Control 991)". The analytical data obtained were: assay by HPLC, 101.0%; spectrophotometric assay, 100.4%. Based on the above results, the raw material was authorized as the Thiamine Hydrochloride Solution Reference Standard (Control 991) of the National Institute of Health Sciences.
The raw material of tocopherol acetate was examined for the preparation of the "Tocopherol Acetate Reference Standard (Control 001)". Analytical data obtained were: IR spectrum, same as that of the Tocopherol Acetate Reference Standard (Control 974); specific absorbance, E/cm% (284 nm) = 43.7; thin-layer chromatography, no impurities were detected until 50 micrograms of the loaded raw material; high-performance liquid chromatography (HPLC), total amount of impurities estimated to be less than 0.6%; assay by HPLC, 101.7%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Reference Standard (Control 001).
The raw material of tocopherol was tested for the preparation of "Tocopherol Reference Standard (Control 991)". Analytical data obtained were: IR spectrum, same as the Tocopherol Reference Standard (Control 941); specific absorbance, E/cm% (292 nm) = 72.9; thin-layer chromatography, no impurities were detected until 50.0 micrograms; high-performance liquid chromatography (HPLC), trace amounts of five impurities were detected and the total amount was estimated to be less than 1.4%; assay by HPLC, 99.9%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Standard (Control 991).
The raw material for prednisolone sodium phosphate was examined for the preparation of the "Prednisolone Sodium Phosphate Reference Standard (Control 001)". The analytical data obtained were: pH, 7.9; optical rotation, [alpha]D20 = +98.0 degrees; UV spectrum, lambda max of 248 nm and specific absorbance in ethanol at 248 nm = 306.7; IR spectrum, same as that of the Prednisolone Sodium Phosphate Reference Standard (Control 892); thin-layer chromatography, five impurities were detected at 200 micrograms; high-performance liquid chromatography (HPLC), total amount of impurities estimated to be less than 3.7%; residual solvent, 0.0% (ethanol) and 0.0% (hexane); loss on drying, 2.7%. Based on the above results, the raw material was authorized as the Prednisolone Sodium Phosphate Reference Standard (Control 001) of the National Institute of Health Sciences.
The raw material of tocopherol was tested for the preparation of "Estradiol Reference Standard (Control 991)". Analytical data obtained were: melting point, 178.5 degrees C: UV spectrum, lambda max of 281 nm and specific absorbance in ethanol at lambda max = 77.7; IR spectrum, same as that of the Estradiol Reference Standard (Control 964); optical rotation, [alpha]D20 = +79.5 degrees; thin-layer chromatography, one impurity was detected; high-performance liquid chromatography (HPLC), total amount of impurities estimated to be less than 0.6%; loss on drying, 3.3%; assay, 100.2% by UV spectrophotometry and 99.9% by HPLC. Based on the above results, the raw material was authorized as the Estradiol Reference Standard (Control 001) of the National Institute of Health Sciences.
The National Institute of Health Sciences Reference Standard for Heparin Sodium (Control 991) was prepared. The potency of heparin sodium for the candidate reference standard was assayed against "Heparin Sodium Reference Standard (Control 871)" by JP Method in collaboration with 4 laboratories, and estimated as 1,453 +/- 25 units per ampoule. The filling amounts of heparin sodium in ampoule was estimated as 7.46 +/- 0.15 mg per ampoule, and the precision of filling into ampoule was about 2.0% as C.V. Based on the above results, the candidate was defined as 1450 units per ampoule, and was authorized as the Heparin Sodium Reference Standard (Control 991) of the National Institute of Health Sciences.
Platelet activating factor (PAF) is immediately degraded and inactivated in the bloodstream by plasma PAF acetylhydrolase (PAF-AH). Although plasma PAF-AH-like activity was secreted in vitro from various cell types such as macrophages and hepatocytes, the exact cellular source(s) of this enzyme activity in vivo remains unclear. There is a naturally-occurring missense mutation (V279F) in the plasma PAF-AH gene in the Japanese population which results in complete loss of the enzyme activity. We analyzed 52 Japanese who had received an allogeneic bone marrow transplant and maintained donor-derived hematopoiesis. Ten recipients had chimeric plasma PAF-AH genotypes between the donor-derived peripheral blood leukocytes and the recipient-derived epithelial cells of buccal mucosa. Multiple regression analysis demonstrated that PAF-AH activity in plasma depended on the donor's genotype (standardized regression coefficient = 0.68, P < 0.0001), but not on the recipient's genotype (p = 0.48). One recipient who was a V279F homozygote in leukocytes and wild type homozygote in buccal mucosa had undetectable PAF-AH activity in plasma. We conclude that most of the PAF-AH activity in human plasma originates from hematopoietic lineage cells.
A Toledo strain cytomegalovirus (CMV) containing the gene for green fluorescent protein (GFP) under the control of elongation factor-1 promoter was used to study infection of human marrow stromal cells. Two stromal cell lines were used: HS-5, which secretes copious amounts of known cytokines and interleukins; and HS-27a, which does not secrete these activities. CMV growth and spread was monitored by counting green plaques and quantitating GFP intensity. Initial studies indicated that, whereas HS-5 and 27a have similar susceptibilities to infection, as evidenced by the same number of GFP+ cells at day 2, HS-5 appears more resistant to growth and spread of CMV. Furthermore, conditioned media from HS-5 (HS-5 CM) inhibited CMV plaque formation in HS-27a, suggesting that factors secreted by HS-5 are responsible for limiting CMV growth. Neutralizing antibodies against interleukin-1alpha (IL-1alpha) and IL-1beta completely blocked the ability of HS-5 CM to limit viral growth, suggesting that IL-1, which is known to be present in HS-5 CM, is responsible for this effect. When exogenous IL-1beta was added to CMV-infected HS-27a, both the number of plaques and the intensity of GFP was significantly reduced in IL-1-treated HS-27a compared with untreated HS-27a (the number of plaques by day 18 was 20 +/- 3 v 151 +/- 12/well, respectively; GFP intensity was 535 +/- 165 v 6,516 +/- 652/well, respectively, in 4 separate experiments). At day 21, when IL-1beta-treated, CMV-infected cultures were passaged and then cultured in the absence of IL-1beta, CMV growth progressed with the kinetics of the original untreated culture, indicating that the IL-1beta effect is reversible. Because HS-27a expresses the type I IL-1 receptor, we speculate that the antiviral effects are mediated through IL-1-induced changes in cellular gene expression. DNA chip analysis of mRNA from IL-1beta-treated and nontreated HS-27a cells has identified some candidate molecules.
This report concerns an ultrastructural study of the synapses present on the surface of somata of normal-looking Betz cells in the fifth layer of motor cortex of seven patients with amyotrophic lateral sclerosis (ALS). Specimens from 12 age-matched, neurologically normal control individuals were included for comparison. Presynaptic terminals on the somata of normal-appearing Betz cells showed a wide range of changes including increased mitochondria, and the dark type of degenerative change of synapses such as dense conglomerates of dark mitochondria with dense cristae and densely aggregated presynaptic vesicles. These alterations were significantly more common in ALS patients than in controls, suggesting that a substantial synaptic change occurs in Betz cells even in the early stage of ALS.
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Cloned human stromal cell lines representing functionally distinct cellular components of the marrow microenvironment were generated to serve as tools for identifying gene products that regulate hematopoiesis. Oligonucleotide arrays, or "gene chips" were used to provide a comprehensive comparison of gene expression among the cell lines. One line, designated HS-5, was found to secrete large amounts of cytokines, and conditioned media from this line was found to support the ex vivo expansion of both immature and mature progenitors. In contrast, a second line, designated HS-27a, does not secrete known cytokines but does support cobblestone area formation by CD34+/38lo cells. HS-27a, but not HS-5, was also found to express hJagged1, a ligand for Notch1, which may function to influence cell fate decisions of hematopoietic precursors. Both cell lines are currently being used to identify other gene products that regulate hematopoiesis and to generate reagents that will allow more formal evaluation of the putative role of hJagged1 in hematopoietic cell fate decisions.
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In this study we investigated the relationship between the development of the olfactory, preoptic, and midbrain gonadotropin-releasing hormone (GnRH) neuronal systems and testicular differentiation in eels (Anguilla japonica) from embryonic stages through adulthood (5.4-50 cm body length). GnRH-synthesizing neuronal populations were first observed in the youngest fish ( approximately 5.0 cm) at the rostrobasal and caudalmost olfactory bulbs immunoreactive to a "promiscuous" (nonspecific) GnRH antiserum (635.5), and in the preoptic area and midbrain tegmentum immunoreactive to chicken GnRH II antiserum. The eel brains lacked salmon and seabream GnRH immunoreactivity. The evidence from our study suggests that the olfactory, preoptic, and midbrain GnRH populations have origins independent from those of proliferative periventricular zones within the brain. However, the olfactory GnRH neurons could have migrated out of the olfactory placodes during ages earlier than those observed in this study. Although all three GnRH neuronal populations contribute to pituitary innervation to some degree, the preoptic GnRH innervation was pronounced in the pituitary when primordial germ cells (animals approximately 5.0 cm) differentiated into male germ cells (animals 14-16 cm) and, therefore, an association can be assumed between preoptic GnRH expression and testicular differentiation in the Japanese eel.
The plasma levels of thromboxane B2 (TxB2) and 6-keto-prostaglandin F1alpha (6-KF) in the peripheral and portal blood increase after an extensive hepatectomy, and even more so in cases with complications. In this cell biological study, we estimated the prostanoids in the portal system to clarify which organ produces them, while also evaluating the effect of a splenectomy in conjunction with an extensive hepatectomy. Our results showed that the level of TxB2 in the splenic vein was significantly higher than that in the mesenteric vein. Furthermore, the TxA2 produced by splenic macrophages after an extensive hepatectomy was significantly more than after a sham operation. We also observed the hepatocyte damage to be less in the group that underwent an 84% hepatectomy and splenectomy than in the group that underwent the same hepatectomy without a splenectomy. It therefore appears important both to suppress the splenic macrophages from producing TxA2 and to prevent remnant hepatic dysfunction after an extensive hepatectomy.