[Two cases of severe liver injuries induced by acetaminophen].
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Acetaminophen↗
Biomedical subjects
M Yamakawa
Publications and source records attributed to M Yamakawa.
Isolation and nucleotide sequence of cecropin B cDNA clones from the silkworm, Bombyx mori.
Two cDNA clones encoding cecropin B, an antibacterial protein, were isolated from a fat body cDNA library of the silkworm, Bombyx mori. Amino acid sequences of these clones, deduced from nucleotide sequences, were identical, including signal peptide regions. However, the nucleotide sequences were different at 30 positions. Deduced amino acid sequences of Bombyx mori cecropin B showed higher homology with cecropins from Lepidoptera than with those from Diptera.
Amino Acid Sequence↗
An immunohistochemical study with an estrogen receptor-related protein (ER-D5) in human colorectal cancer.
The ER-D5 antigen is a protein associated with the estrogen receptor that is present only in estrogen receptor-positive tissues. To clarify the estrogen receptor in colon cancer, the localization of ER-D5 was studied immunohistochemically. Forty-three of 171 (25.1%) specimens of colon cancer showed reactivity for ER-D5. Reactivity was seen only in the cytoplasm. No reactivity was seen in cancer limited to the mucosa or in adenoma, but submucosal cancers showed a rate of positivity similar to cancers that involved lamina muscularis and beyond. Estradiol staining was done on serial sections from 56 specimens. There was a significant relationship between reactivity for estradiol and that for ER-D5. In the 15 specimens where both ER-D5 and estradiol were positive, the distribution of estradiol was similar to that of ER-D5. It was concluded that the immunohistochemical localization of ER-D5 indirectly shows that of the estrogen receptor in colorectal cancer tissues.
Adenocarcinoma↗
Significance of basolateral domain of polarized MDCK cells for Sendai virus-induced cell fusion.
Fusion (fusion from within) of polarized MDCK monolayer cells grown on porous membranes was examined after infection with Sendai viruses. Wild-type virus, that buds at the apical membrane domain, did not induce cell fusion even when the F glycoprotein expressed at the apical domain was activated with trypsin. On the other hand, a protease activation mutant, F1-R, with F protein in the activated form and that buds bipolarly at the apical and basolateral domains, caused syncytia formation in the absence of exogenous protease. Anti-Sendai virus antibodies added to the basolateral side, but not at the apical side, inhibited cell fusion induced by F1-R. In addition, T-9, a mutant with bipolar budding phenotype of F1-R but with an uncleavable F protein phenotype like wild-type virus, induced cell fusion exclusively when trypsin was added to the basolateral medium. By electron microscopy, cell-to-cell fusion was shown to occur at the lateral domain of the plasma membrane. These results indicate that in addition to proteolytic activation of the F protein, basolateral expression of Sendai virus envelope glycoproteins is required to induce cell fusion.
Animals↗
Budding site of Sendai virus in polarized epithelial cells is one of the determinants for tropism and pathogenicity in mice.
Wild-type Sendai virus fusion (F) glycoprotein requires trypsin or a trypsin-like protease for cleavage-activation in vitro and in vivo, respectively. The virus is pneumotropic in mice and buds at the apical domain of bronchial epithelial cells. On the other hand, the F protein of the protease-activation host range mutant, F1-R, is cleaved by ubiquitous proteases present in different cell lines and in various organs of mice. F1-R causes a systemic infection in mice and the mutant buds bipolarly at the apical and basolateral domains of infected epithelial cells. The enhanced cleavability of the F protein of F1-R has been shown to be a primary determinant for pantropism. Additionally, it has been postulated that bipolar budding of F1-R is required for the systemic spread of the virus and it has been attributed to mutations in the matrix (M) protein of F1-R (Tashiro et al., Virology 184, 227-234, 1991). In this study protease-activation mutants (KD series) were isolated from wild-type virus. They were revealed to bud at the apical domain, and the F protein was cleaved by ubiquitous proteases in mouse organs. The KD mutants were exclusively pneumotropic in mice following intranasal infection, whereas they caused a generalized infection when inoculated directly into the circulatory system. Comparative nucleotide sequence analysis of the F gene of the KD mutants revealed that the deduced amino acid substitutions responsible for enhanced cleavability of the F protein occurred removed from the cleavage site. Mutations were not at all found in the M gene of the KD mutants analyzed, in support of the role of the M protein of F1-R and of a revertant T-9 derived from the latter in bipolar budding. These results suggest that bipolar budding is necessary for the systemic spread of F1-R from the lungs and that apical budding by wild-type virus and the KD mutants leads to respiratory infections. Differential budding at the primary target of infection, in addition to the cleavage-activation of the F protein in mouse organs, is therefore also a determinant for tropism and pathogenicity of Sendai virus in mice.
Amino Acid Sequence↗
Impaired metabolism of high density lipoprotein in uremic patients.
We measured lipoproteins, apolipoproteins, lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL), lecithin: cholesterol acyltransferase (LCAT) and parameters of calcium metabolism to evaluate the roles of these enzymes and hypertriglyceridemia for impaired high-density lipoprotein (HDL) metabolism in chronic renal failure, and to examine the impact of altered calcium homeostasis on the lipoprotein-regulating enzymes. The subjects were 25 healthy volunteers and 66 uremic patients, 24 treated with hemodialysis (HD) and 42 with continuous ambulatory peritoneal dialysis (CAPD). Lipoprotein analysis revealed: (1) reduction in HDL cholesterol especially in HDL2 subfraction; (2) increase in HDL triglyceride; and (3) decreased ratio of HDL2 cholesterol to HDL3 cholesterol in both HD and CAPD patients. Simple regression analysis showed: (1) a positive correlation between VLDL triglyceride and triglyceride/cholesterol ratio of HDL; (2) positive correlations of LPL level in post-heparin plasma to cholesterol concentrations in HDL2, HDL3 and total HDL, and to apolipoproteins A-I and A-II; and (3) inverse correlations of HTGL to HDL2 cholesterol and to the ratio of HDL2 cholesterol/HDL3 cholesterol. Multiple regression analysis of HDL cholesterol indicated positive association with LPL and inverse correlation with VLDL triglyceride. Four variables including LPL, HTGL, LCAT and VLDL triglyceride explained 51.5% of the variation of HDL cholesterol. HDL2 cholesterol was associated positively with LPL and negatively with VLDL triglyceride in the model. HDL3 cholesterol was associated positively with LPL, HTGL and LCAT and inversely with VLDL triglyceride. Stepwise multiple regression analysis indicated that independent predictors of HTGL were gender, parathyroid hormone levels by a mid-portion assay, ionized calcium and age, and that those of LCAT were ionized calcium and age.(ABSTRACT TRUNCATED AT 250 WORDS)
Apolipoproteins↗
Myosin light chain-2 mutation affects flight, wing beat frequency, and indirect flight muscle contraction kinetics in Drosophila.
We have used a combination of classical genetic, molecular genetic, histological, biochemical, and biophysical techniques to identify and characterize a null mutation of the myosin light chain-2 (MLC-2) locus of Drosophila melanogaster. Mlc2E38 is a null mutation of the MLC-2 gene resulting from a nonsense mutation at the tenth codon position. Mlc2E38 confers dominant flightless behavior that is associated with reduced wing beat frequency. Mlc2E38 heterozygotes exhibit a 50% reduction of MLC-2 mRNA concentration in adult thoracic musculature, which results in a commensurate reduction of MLC-2 protein in the indirect flight muscles. Indirect flight muscle myofibrils from Mlc2E38 heterozygotes are aberrant, exhibiting myofilaments in disarray at the periphery. Calcium-activated Triton X-100-treated single fiber segments exhibit slower contraction kinetics than wild type. Introduction of a transformed copy of the wild type MLC-2 gene rescues the dominant flightless behavior of Mlc2E38 heterozygotes. Wing beat frequency and single fiber contraction kinetics of a representative rescued line are not significantly different from those of wild type. Together, these results indicate that wild type MLC-2 stoichiometry is required for normal indirect flight muscle assembly and function. Furthermore, these results suggest that the reduced wing beat frequency and possibly the flightless behavior conferred by Mlc2E38 is due in part to slower contraction kinetics of sarcomeric regions devoid or partly deficient in MLC-2.
Allosteric Regulation↗
Lymph node interdigitating cell sarcoma. A case report.
A 54-year-old man was admitted because of right supraclavicular lymphadenopathy of some weeks duration. Computed axial tomography revealed a large multinodular lesion in a supraclavicular lymph node. The patient then had a supraclavicular lymph node biopsy. Light microscopy showed a tumor whose structure was suggestive of an interdigitating cell sarcoma. Enzyme and immunohistochemical analysis showed that the tumor cells possessed membranous adenosine triphosphatase activity, intracytoplasmic S100 protein, surface CD1a and CD4 antigens, and HLA-DR antigen. Ultrastructural examination showed that the cells exhibited many interdigitating cytoplasmic extensions, but no Birbeck granules. DNA content analysis of the tumor cells proved that the cells were malignant. These data are consistent with derivation from a lymph node interdigitating cell.
Biomarkers↗
Clinical effects of long-term use of neutralized dialysate for continuous ambulatory peritoneal dialysis.
The long-term effects of neutralized dialysate used in continuous ambulatory peritoneal dialysis (CAPD) were evaluated in 8 well-controlled patients. Twelve milliliters of 8.4% sodium bicarbonate was added to Dianeal PD-1 immediately before every administration. The final pH was 6.8 and the concentration of sodium bicarbonate was 6 mmol/l. The final sodium level was 138 mEq/l. This dialysate was used for 5 months. For 2 months before and 3 months after this period, Dianeal PD-2 was used as the dialysate for comparison. Blood bicarbonate levels significantly improved during the use of the neutralized dialysate. Blood sodium, chloride and magnesium levels and the effluent volume significantly increased. Sodium balance improved during the period when neutralized dialysate was used. Total leukocyte counts in the effluent decreased, and leukocyte viability increased. Abdominal distention, abdominal pain during instillation, nausea and headache improved. No side effects, including peritonitis, occurred during the trial of neutralized dialysate. The results suggest that this dialysate was less irritating to the peritoneal membrane than the control dialysate and that the therapeutic effects were satisfactory.
Blood Urea Nitrogen↗
Two cases of persistent hypouricemia associated with diabetes mellitus.
Two patients with diabetes mellitus had persistent hypouricemia due to increased urate clearance; the degree of the apparent renal hypouricemia with uricosuria was quite mild. At the onset of diabetes, their serum urate levels were normal. Even after good diabetes control in both cases, hypouricemia continued. Based on the pharmacological evaluation in both patients, pyrazinamide administration could partially decrease urate clearance, however, suppression by pyrazinamide was less than in normal subjects, and probenecid increased urate clearance. These results suggest that the present cases had a renal abnormality affecting tubular presecretory reabsorption of urate, which might be due to diabetes mellitus.
Aged↗
3 beta-Hydroxysialic acid glycosides. I. Calcium-binding ability and chemical and enzymatic stabilities.
Methyl alpha- and beta-glycosides of N-acetylneuraminic acid (Neu5Ac) and N-acetyl-3 beta-hydroxyneuraminic acid (Neu5Ac beta 3OH) (1-4) were prepared to evaluate their calcium-binding ability. (Methyl alpha-glucopyranosidonyl) alpha- and beta-, and 4-methylumbelliferyl alpha-glycosides of Neu5Ac and Neu5Ac beta 3OH (5-10) were also synthesized for the comparison of chemical and enzymatic stabilities, respectively. Methyl beta-glycosides of Neu5Ac and Neu5Ac beta 3OH, 3 and 4, respectively, showed intense calcium-binding abilities, while no such ability was observed in the corresponding alpha-glycosides, 1 and 2. The Neu5Ac beta 3OH glycosides, 6, 8, and 10, showed much stronger resistance to acidic hydrolysis and sialidase digestion than the corresponding Neu5Ac glycosides, 5, 7, and 9.
Animals↗
Syntheses of recombinant yellowtail and flounder growth hormones in Escherichia coli.
For syntheses of recombinant yellowtail and flounder growth hormones (r-yGH and r-fGH) in E. coli, expression plasmids were constructed. The expression level of r-yGH and r-fGH in the host cells were very high, reaching 15 and 8% of the total protein, respectively. These product proteins were accumulated in inclusion bodies in the cells. The recombinant hormones were isolated from the pellets ina glutathione reduction/oxidation buffer. The refolded hormones were further purified by DEAE-Toyopearl 650M chromatography to homogeneity. The purified r-yGH and r-fGH were composed of 188 and 174 amino acid residues, respectively, having amino-terminal sequences starting with methionine. The recombinant hormones had potent growth-promoting activities on juvenile rainbow trout Salmo gairdneri in a dose-dependent manner.
Animals↗
Renal handling of urate in two patients with hyperuricemia and primary hyperparathyroidism.
Two patients with primary hyperparathyroidism had hyperuricemia due to the decrease in urate clearance. In analysis by 4-component model system, the tubular secretion of urate commonly decreased without changes in either filtered urate or presecretory reabsorption of urate. Both patients had a reduction of urea clearance, and both parathyroidectomy in the former case and intravenous infusion of saline in the latter case could reduce the serum urate level associated with the increase in the ratio of urate clearance to creatinine clearance. It is of interest that the former case with a higher serum urate level had a relatively higher postsecretory reabsorption, even with the decrease in tubular secretion of urate. However, the latter patient with a lower serum urate level had a decrease in postsecretory reabsorption of urate in proportion to the decrease in tubular secretion. These results suggest that in hyperuricemia patients with primary hyperparathyroidism, the reduction of tubular urate secretion via hypoperfusion of the capillary network is typically present, however, the severity of the hyperuricemia might be dependent on the dysfunction of the postsecretory reabsorption of urate.
Aged↗
[Upper gastrointestinal complications in uremic patients with dialysis].
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Benzamidines↗
Complement activation in the follicular light zone of human lymphoid tissues.
A comparative immunohistochemical study of the distribution pattern of complement components and regulatory proteins within secondary lymphoid follicles was performed by the immunoperoxidase technique. Fifteen lymphoid tissues including appendices. Peyer's patches and tonsils were analysed. Sixty secondary lymphoid follicles with evident polarity, that is, the distinct coexistence of a light zone, dark zone and mantle zone in the same lymphoid follicle, were tested with single antibodies. The light zones were consistently immunostained in a dendritic meshwork pattern with all antibodies. The immunostaining patterns were classified into two major groups based on the immunoreactivity of the dark zone. One immunostaining pattern was characterized by no immunostaining of the dark zone to the majority of the antigens. The second group was characterized by a diffusely weak to moderate dendritic meshwork pattern of the dark zone to some of the immunostainings of C9 (monoclonal), S-protein, and DF-DRC1, and all immunostainings of CR1 (CD35), Ber-Mac-DRC (CD35), CR2 (CD21), and R4/23. All four complement regulatory proteins were localized by immunoelectron microscopy attached to the cell surface of the cells, including follicular dendritic cells, in the light zone. Our data indicate that there is an evident functional difference between the light zone and the dark zone, and that complete activation of the complement system occurs only in the light zone.
Antigens, Differentiation, B-Lymphocyte↗
High serum lipoprotein(a) concentrations in uremic patients treated with continuous ambulatory peritoneal dialysis.
We measured serum lipoprotein(a) [Lp (a)] concentrations in 50 uremic patients treated on continuous ambulatory peritoneal dialysis (CAPD) and compared them with those in 29 uremic patients on hemodialysis (HD) and those in 62 normal controls. The median values were 47.9 mg/dl in CAPD patients, 25.2 mg/dl in HD patients, and 11.7 mg/dl in controls, respectively. These differences were statistically significant when assessed by Kruskal-Wallis test (p < 0.0001). Thirty-five out of 50 patients on CAPD (70%) and 12 out of 29 patients on HD (41%) had Lp(a) concentrations above 30 mg/dl, whereas these high values were observed in only 15% of normal controls. This difference in prevalence of high Lp(a) was also significant by 2 x 3 chi-square test (p < 0.01). There was a significant positive correlation between Lp(a) and apolipoprotein B (r = 0.517, p < 0.0001). In CAPD patients, 9 with ischemic heart disease had a significantly higher median Lp(a) than those without it (67.4 vs 40.9 mg/dl, p < 0.01 by Mann-Whitney U-test). These results suggest that high levels of serum Lp(a) might contribute to an increased risk for ischemic heart disease in CAPD patients, and that there may be a relationship between Lp(a) and apolipoprotein B metabolism in CAPD patients.
Adult↗
[A case of ulcerative colitis with localised giant inflammatory polyposis].
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Adult↗
Localization of blood coagulation factors in the germinal centers of human Peyer's patches.
The immunohistochemical distribution of 15 blood coagulation factors in the germinal centers (GCs) of human Peyer's patches (PPs) was studied. Although factor VIII, active alpha-thrombin, and fibrinogen were hardly evident in the GCs, the majority of coagulation factors, such as kallikrein, high-molecular-weight kininogen, factors XII, X, IX, VII, V, XIIIa and XIIIb, prothrombin, anti-thrombin III and inactive alpha-thrombin were found, showing a lace-like staining pattern similar to that obtained with a monoclonal antibody, R4/23, specific for follicular dendritic cells (FDCs) in the GCs. By immunoelectron microscopy, positive reactions for factor X and XIIIa were found on the surfaces of FDCs, GC cells, and/or in the intercellular spaces of GCs, being especially marked on the surface of the labyrinth-like structure of FDCs. It is concluded that a majority of coagulation factors are localized in the GCs of human PPs. Furthermore, it is suggested that some of these coagulation factors have a close topographical relationship with FDCs.
Antibodies, Monoclonal↗