[A case of Lambert-Eaton myasthenic syndrome during malignant lymphoma].
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Aged↗
Biomedical subjects
S Hatakeyama
Publications and source records attributed to S Hatakeyama.
Biological and physicochemical characterization of recombinant human erythropoietins fractionated by Mono Q column chromatography and their modification with sialyltransferase.
Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. On the other hand, an inverse relationship between the in vitro bioactivity and sialic acid content of EPO was observed. Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected.
Animals↗
Nitric oxide synthase-containing magnocellular neurons of the rat hypothalamus synthesize oxytocin and vasopressin and express Fos following stress stimuli.
We investigated the chemical and anatomical features of nitric oxide synthase (NOS)-containing neurons in the paraventricular and supraoptic nuclei in the rat hypothalamus using combinations of enzyme histochemistry, in situ hybridization and immuno-histochemistry. Neurons expressing NOS mRNA completely overlapped with NADPH-diaphorase-positive neurons. Topographical distribution of NOS was segregated from that of CRF-containing parvicellular neurons in the posterior paraventricular nucleus but overlapped with that of magnocellular neurons. In the paraventricular nucleus, 70% of oxytocin neurons contained NOS, which corresponded to one half of NOS neurons. About one third of vasopressin-immunoreactive neurons were NADPH-diaphorase-positive and the same proportion of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. In the supraoptic nucleus, 50% of oxytocin neurons were NADPH-diaphorase-positive, which corresponded to 40% of NOS neurons. About 25% of vasopressin neurons were NADPH-diaphorase-positive, and 30% of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. When NADPH-diaphorase histochemistry was performed first, subsequent immunostaining was markedly perturbed. Using fluoro-gold as a retrograde tracer, 4% of NADPH-diaphorase-positive neurons were shown to contribute to the descending projection to the spinal cord. About 40%-50% of NADPH-diaphorase-positive neurons exhibited Fos immunoreactivity after injection of lipopolysaccharide or hypertonic saline, while only 10%-15% of these neurons expressed Fos in response to immobilization or pain. Endogenous NO may be involved in the regulation of magnocellular functions, especially when the internal environment is disturbed.
Animals↗
Functional significance of the Fas molecule in naive lymphocytes.
The Fas molecule mediates apoptotic signal in many cell types. Mouse mutations (lpr, lprcg, gld), which impair the function of Fas, cause spontaneous autoimmune disease. We generated Fas-deficient (Fas-/-) mice by homologous recombination. In embryonic stem cells Fas-/- mice developed lpr-like disease, confirming that the abnormality of Fas is causal in the lpr phenotype. We also made Fas-/- chimeric mice composed of a mixture of Fas+/+ and Fas-/- cells. The chimeric mice also showed the lpr phenotype. In Fas-/-, chimeric mice, the Fas-deficient population expanded progressively among mature T and B lymphocytes. The expansion of Fas-deficient lymphocytes occurred at the naive, pre-primed, lymphocyte stage. These results suggest that the Fas molecule functions not only after antigenic stimulation, as previously hypothesized, but also at the naive lymphocyte stage.
Animals↗
Fgr expression restricted to subpopulation of monocyte/macrophage lineage in resting conditions is induced in various hematopoietic cells after activation or transformation.
The c-fgr gene product (Fgr) is a member of the src-family of protein tyrosine kinases. We have established a monoclonal antibody (2H2) which recognizes the unique N-terminal domain of the murine Fgr. In the present study, using immunohistochemical analysis and immune complex kinase assay with the 2H2, we investigated expression of Fgr in various cell populations and tissues in a murine system. In resting conditions, Fgr expression was confined to subsets of a monocyte/macrophage lineage. Thus, Fgr+ cells were detected in paracortical areas and medullas of lymph nodes, but seen only in marginal zones of the spleen and the medulla of the thymus. No Fgr+ macrophage was detected in other tissues, Peyer's patches, brain, heart, lung, liver, pancreas, kidney and peritoneal cavity. However, immune complex kinase assay revealed that, upon stimulation, T and B cells as well as peritoneal macrophages expressed significant levels of Fgr molecules. Transformed cell lines of lymphoid origin, EL-4 and LK35.2, which are T and B lineage lymphomas, respectively, also expressed Fgr molecules. Thus, various cells of hematopoietic origin appeared to possess a potentiality to express Fgr following activation or transformation. The present findings may help elucidate the functional significance of Fgr in immunologically committed cells in either activated or non-activated conditions.
Animals↗
Correlation between serum carnitine levels and erythrocyte osmotic fragility in hemodialysis patients.
The relationship between serum carnitine levels and erythrocyte osmotic fragility was investigated in 26 chronic hemodialysis patients (10 males and 16 females, mean age: 57.3 +/- 13.5 years). Serum total-carnitine (TC), free-carnitine (FC) and acyl-carnitine (AC) levels were determined by a spectrophotometric method. Erythrocyte osmotic fragility was measured with a coil planet centrifuge. Serum TC levels were 39.9 +/- 13.4 mumol/l (mean +/- SD), FC levels were 21.8 +/- 7.8 mumol/l and AC levels were 18.0 +/- 9.6 mumol/l. The mean hemolysis end point (HEP) was 67.4 +/- 5.4 mOsM, the hemolysis maximum point (HMP) was 86.3 +/- 5.4 mOsM and the hemolysis start point (HSP) was 101.2 +/- 4.4 mOsM. Each hemolysis point in hemodialysis patients was elevated in comparison with the normal range. There were no significant differences in hemolysis points between a recombinant human erythropoietin (rhEPO)-treated group and nontreated group. HEP correlated with serum TC (r = -0.56, p < 0.01) and AC levels (r = -0.58, p < 0.01). HMP correlated with serum TC (r = -0.42, p < 0.05) and FC levels (r = -0.41, p < 0.05). Dose requirement of rhEPO maintaining target hematocrit correlated with serum TC (r = 0.54, p < 0.05) and FC levels (r = 0.50, p < 0.05). These data support that low serum carnitine levels accelerate erythrocyte osmotic fragility. Carnitine may contribute to the metabolism of erythrocyte membrane and have an impact on the efficacy of rhEPO in correcting renal anemia.
Adult↗
Synthetic studies of vitamin D analogs. XXII. Synthesis and antiproliferation activity of putative metabolites of 1 alpha, 25-dihydroxy-22-oxavitamin D3.
As putative metabolites of 1 alpha,25-dihydroxy-22-oxavitamin D3 (OCT), 24-hydroxylated OCT in 24(R) and 24(S) forms, 24-ketoOCT, 26-hydroxylated OCT in 25(S) and 25(R) forms, pentanorOCT and pentanor-ketoOCT were synthesized from the steroidal 20(S)-alcohol. Their antiproliferation activities towards human promyelocytic leukemia cells (HL-60 cells) are also reported. Oxidized derivatives at the C-24 position, 24-ketoOCT, 24(R)-hydroxylated OCT and 24(S)-hydroxylated OCT, showed activities comparable to or slightly weaker than that of OCT, while 26-hydroxylated OCT was less active than OCT. Truncated OCT, pentanor OCT and pentanor-ketoOCT, were inactive at 10(-7)-10(-10) M.
Animals↗
Retinoic acid enhances expression of bone morphogenetic protein-2 in human adenocarcinoma cell line (HSG-S8).
Expression of bone morphogenetic protein (BMP)-2 mRNA was stimulated by retinoic acid in human adenocarcinoma cell line, HSG-S8, in a dose-dependent manner. Northern blot analysis demonstrated that retinoic acid most strongly increased the level of BMP-2 mRNA 6 h after the treatment and the stimulatory effect was maintained at 48 h. The mature peptides of 16 and 18 kDa molecular masses of BMP-2 were also increased in the conditioned medium by the treatment of retinoic acid on western blotting. The proliferation of HSG-S8 cells was inhibited by retinoic acid, however, retinoic acid did not cause morphological change showing cellular differentiation. 1 alpha, 25(OH)2D3, like retinoic acid, clearly increased the mRNA level of BMP-2, whereas dibuthryl cyclic AMP remarkably diminished it, and bromodeoxyuridine had no effect on the expression of BMP-2 mRNA.
Adenocarcinoma↗
Identification and expression of the Neurospora crassa mei-3 gene which encodes a protein homologous to Rad51 of Saccharomyces cerevisiae.
The mei-3 gene of Neurospora crassa encodes a homolog of the Escherichia coli RecA and Saccharomyces cerevisiae Rad51 proteins, which are required for recombination and repair of DNA double-strand breaks. To determine the molecular function of MEI3 protein, anti-MEI3 antibody was prepared and used in Western blot analysis. The antibody cross-reacted only with crude extracts prepared from perithecia, the fruiting bodies of Neurospora. The molecular weight of the MEI3 protein was estimated to be 38 kDa. Transformation experiments showed that a DNA fragment longer than previously reported was needed to complement the mei-3 mutation. On sequencing cDNA and genomic DNA, one open reading frame (ORF) was found, which consists of three exons interrupted by two small introns. This ORF encoded a MEI3 protein of 353 amino acids, and the inferred MW of 38 kDa is in good agreement with the results from Western blot analysis. Comparisons of MEI3 with other Rad51 homologs indicated that MEI3 protein contains the two conserved core domains (I and II) generally observed in Rad51 homologs in eukaryotes. Northern blot analysis showed that expression of mei-3 was raised remarkably after UV-irradiation or methyl methanesulfonate (MMS)-treatment. The transcript size was 1.6 kb and this was also larger than was reported previously.
Amino Acid Sequence↗
Essential role for ZAP-70 in both positive and negative selection of thymocytes.
During thymic development, T cells that can recognize foreign antigen in association with self major histocompatibility complex (MHC) are selected for survival (positive selection) and autoreactive T cells are eliminated (negative selection). Both of these selective events are mediated by interaction between the T-cell receptor (TCR) and the peptide-MHC complex. But the signalling pathways that lead to cell survival or to cell death are still unclear. ZAP-70 is a protein tyrosine kinase (PTK) that is associated with the TCR signalling subunits (CD3 and zeta) and is expressed in T cells and natural killer cells. It has been shown that ZAP-70 plays a crucial role in T-cell activation and development. Here we show that mice lacking ZAP-70 had neither CD4 nor CD8 single-positive T cells, but human ZAP-70 reconstituted both CD4 and CD8 single-positive populations. Moreover, ZAP-70-/- thymocytes were not deleted by peptide antigens. Natural killer cell function was intact in the absence of ZAP-70. These data suggest that ZAP-70 is a central signalling molecule during thymic selection for CD4 and CD8 lineage.
Animals↗
Paradoxical effect of Sudan III on the in vivo and in vitro genotoxicity elicited by 7,12-dimethylbenz(a)anthracene.
Effect of the induction of drug metabolizing enzymes by Sudan III on the in vivo and in vitro genotoxicity elicited by 7,12-dimethyl-benz(a)anthracene (DMBA) was investigated. A significant suppression of DMBA-induced micronucleated reticulocytes was observed in C57BL/6 mice treated with Sudan III intraperitoneally for 3 or 5 days before injection of the DMBA. However, the preincubation of DMBA with hepatic microsomes from Sudan III-treated rats caused a marked increase in the in vitro mutagenicity in the Ames assay, paradoxically. Sudan III was found to induce CYP 1A1, 7-ethoxycoumarin O-deethylase activity as well as both UDP-glucuronyl transferase and glutathione S-transferase activities. The increase of mutagenicity of DMBA observed in the Ames assay using hepatic microsomes from Sudan III-treated rats was inhibited by the addition of uridine 5'-diphosphoglucuronic acid or reduced glutathione with cytosol. Mutagenic metabolites of DMBA formed by CYP1A1 appeared to be effectively detoxified by these phase II enzymes. The results of this study suggest that Sudan III-induced prevention of in vivo mutagenesis is due to the induction of both CYP 1A1 and detoxifying phase II enzymes. The induced CYP1A1 may accelerate formation of active metabolic intermediates, but phase II enzymes are also induced and detoxify these intermediates to inactive metabolites. This would reduce residence time of the carcinogen in the body and the time of exposure to active metabolites for target organs.
7-Alkoxycoumarin O-Dealkylase↗
[Treatment of aspiration pneumonia with low-dose methylprednisolone and antibiotics].
Low-dose methylprednisolone and antibiotics were used to treat 30 patients with aspiration pneumonia, in a prospective, randomized, double-blind trial with placebo control. All patients received clindamycin phosphate 1200 mg per day. In addition, 15 patients received methylprednisolone 20 mg per day for three days and the other 15 patients received placebo according to the same schedule. In the methyl prednisolone group, CRP had decreased (p < 0.05) from 12.7 +/- 9.8 to 6.4 +/- 5.4 mg/dl day 4, neutrophil elastase had decreased (p < 0.05) from 402 +/- 304 to 231 +/- 64 micrograms/dl by day 4 and to 184 +/- 59 micrograms/dl by day 7, maximum body temperature had decreased (p < 0.01) from 37.9 +/- 1.1 to 36.8 +/- 0.6 degrees C by day 7, and the pneumonia score had improved (p < 0.01) from 11.8 +/- 3.0 to 8.6 +/- 2.4 by day 4. In the placebo group, there were no significant improvements by those days. We conclude that low-dose methylprednisolone therapy with antibiotics is effective against aspiration pneumonia.
Aged↗
[A case of pulmonary blastoma coexisting with well-differentiated adenocarcinoma].
A 66-year-old man came to our hospital because of hemoptysis and fever. Chest radiograph and CT scan showed a large circumscribed shadow in the posterior segment of the right upper lobe. Bronchoscopy revealed bronchial compression and stenosis. The histopathological specimen obtained by transbronchial biopsy showed total necrosis, but cytological examination of the bronchial lavage specimen showed class 5 adenocarcinoma. Right upper lobectomy was done, and regional lymph nodes were removed. The resected tumor was found to be a pulmonary blastoma by histopathological examination. The main tumor was composed of malignant epithelial and mesenchymal elements with rhabdoid differentiation and chondroid tissue, the former of which looked like fetal lung tissue. This case is interesting, because the fact that the adenocarcinoma and pulmonary blastoma were close together may be related to the histogenesis of pulmonary blastoma.
Adenocarcinoma↗
[A case of cilostazol-induced pneumonitis].
A 73-year-old man had been treated with cilostazol for antithrombotic therapy after a myocardial infarction. Seventy days after the start of cilostazol therapy, he developed dyspnea, dry cough, and fever. He was admitted to our hospital on April 13, 1923. Chest radiography and CT revealed a ground glass appearance. All drugs except isosorbide dinitrate were discontinued and he was treated with steroids under the presumptive diagnosis of drug-induced pneumonitis. Steroid therapy was effective. The result of a lymphocyte stimulation test was positive for cilostazol. Based on the above findings, cilostazol-induced pneumonitis was diagnosed. To our knowledge, there have been no previous reports of cilostazol-induced pneumonitis.
Aged↗
[A case of pulmonary tuberculosis associated with triple cancer].
A 76-year-old man came to our hospital complaining of bloody sputum and anterior chest pain. He had undergone operations for rectal cancer six years previously and for gastric cancer nine months previously. His chest X-ray film showed a mass shadow in the left lower field and a small nodular shadow in the right middle field. After treatment with antibiotics and antituberculosis drugs, symptoms and laboratory findings improved and left mass shadow on the chest X-ray film began to resolve. Adenocarcinoma of the lung was diagnosed after a transbronchial lung biopsy from the right S3a. An operation was scheduled for two months later, but a new mass shadow appeared in the right lower field. Right upper lobectomy with mediastinal lymph node dissection and partial resection of the right S9 was done. The surgical specimens revealed well-differentiated adenocarcinoma from the right S3a and tuberculosis from the right S1, S2, and S9. A recent increase in multiple cancers has been noticeable, but cases of triple cancer concurrent with tuberculosis are rare. When chest-radiographic abnormalities unrelated to the original tumor occur in lung cancer patients, a second primary cancer should be considered. It is also important to determine if they are caused by intra-lung metastases or by some other condition, such as exacerbation of pulmonary tuberculosis.
Adenocarcinoma↗
[Hereditary hemorrhagic telangiectasia (HHT)].
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Humans↗
A potential peptide vaccine against two different strains of influenza virus isolated at intervals of about 10 years.
We have developed a strategy for making synthetic peptide vaccines, in which a peptide, HA127-133, derived from the hemagglutinin (HA) of A/Aichi/2/68(H3N2) influenza virus (Aichi/68) is introduced into the Ab binding component consisting of 43-46 and 54-58 residues of a pigeon cytochrome c analogue peptide, 46F50V54A. Indeed, this hybrid peptide, 46F/HA127-133/54A, induced impressive T-cell responses and antibody production neutralizing infectivity of Aichi/68 in vitro. In a subsequent study we found that 46F/HA127-133/54A(18mer) peptide antigen, which had been prepared by substitution at the central five residues of 46F50V54A with HA127-133, generated T-cell responses and neutralizing antibody responses as well. On the basis of these prior findings, in the present study we analyzed immunopotency of 46F/HA127-133/54A(18mer) in vivo administered in several ways to I-Ab mice. We show herein that this peptide vaccine loaded in multilamellar liposomes without adjuvant protects the mice against infection with Aichi/68 within 2 weeks after final immunization. Further, this peptide vaccine was shown to be effective in preventing infection with a naturally occurring antigenic variant, A/Texas/1/77(H3N2), carrying the same sequence at 127-133 of the HA as Aichi/68 virus. Since this part of the HA is relatively conserved among H3 subtype influenza viruses, our peptide vaccine may become the basis for a new strategy to prepare effective vaccines that will overcome the ineffectiveness of classical vaccines attributable to antigenic drift of influenza viruses.
Animals↗
The murine c-fgr gene product associated with Ly6C and p70 integral membrane protein is expressed in cells of a monocyte/macrophage lineage.
The c-fgr gene is a member of the Src family of protooncogene tyrosine kinases. A monoclonal antibody (2H2) that recognizes the specific region of the N-terminal domain of the murine c-fgr gene product (Fgr) has been established. With an immune complex kinase assay in a monocytic leukemia cell line, 2H2 monoclonal antibody was shown to precipitate a 59-kDa protein that corresponds in molecular mass to murine Fgr. Fgr was expressed highly in lymph nodes, slightly in spleen and peripheral blood leukocytes, and barely in the thymus and was not detected in bone marrow. In the presence of a mild detergent, Fgr was coimmunoprecipitated with a 70-kDa protein (p70) or with p70 plus several other molecules that were expressed on the cell-surface membrane of macrophage tumor cell lines PU5-1.8 and J774.1, respectively. By contrast, Fgr was not coimmunoprecipitated with a low-affinity receptor for the Fc portion of IgG that is associated with human Fgr. The molecule was also coimmunoprecipitated with the Ly6C molecule from a macrophage cell line (J774.1) that showed protein-tyrosine kinase activity. Peptide mapping revealed that this kinase activity was derived from Fgr. The similarity of relationship between this intramembrane p70 and/or Ly6C and cytoplasmic Fgr to relationships previously reported between T-cell antigen receptor complex, including CD4 and CD8 coreceptors, and Lck or Fyn in T cells and between surface IgM and Lyn or Blk in B cells, suggests that the Fgr and p70 or Ly6C are, indeed, associated with each other and in the murine system may be responsible for recognition of extracellular substances (either cellular or noncellular) and for signal transduction in cells of monocyte/macrophage lineage.
Animals↗