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Biomedical subjects

M Kawagoe

Publications and source records attributed to M Kawagoe.

At least 55 records · Page 3Linked to original sources

Continuous removal of anti-DNA antibody, using a new extracorporeal immunoadsorption system, in patients with systemic lupus erythematosus.

We performed selective and continuous immunoadsorption of anti-DNA antibodies from the blood of 6 patients with systemic lupus erythematosus, using a newly developed extracorporeal immunoadsorption system equipped with twin dextran sulfate-cellulose columns with an automated regenerating unit. Levels of anti-DNA, which were initially high, were rapidly diminished after 2-4 apheresis procedures in each patient; in 3 patients with proteinuria and 4 patients with lymphocytopenia, these symptoms also improved. Analysis of the kinetics and the adsorbed amounts of anti-DNA during the apheresis indicates that both the intravascular and the extravascular pool of anti-DNA are reduced with this potent apheresis technique.

Adult↗

Comparative effects of N,N-disubstituted dithiocarbamates on excretion and distribution of cadmium in mice.

Sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), sodium N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD) and sodium N-p-methoxybenzyl-D-glucamine dithiocarbamate (MeOBGD) were evaluated for their efficacy in the distribution and excretion of cadmium in mice exposed to cadmium. Mice were injected i.p. with 109CdCl2 (1 mg Cd/kg and 74 kBq of 109Cd/animal) and 30 min or 24 h later, they were injected with chelating agents (400 mumol/kg). At 30 min after treatment with cadmium, these chelating agents all significantly enhanced the biliary excretion of cadmium, and HBGD and CBGD significantly increased the urinary excretion of the metal. At 24 h after cadmium injection, BGD, HBGD, and MeOBGD significantly increased the biliary excretion of cadmium and HBGD was the most effective on the biliary excretion of the metal. These chelating agents were effective in mobilizing cadmium from the liver at 30 min after cadmium treatment. At 24 h after cadmium treatment, HBGD and MeOBGD effectively depressed cadmium content in the liver and only HBGD among these chelating agents significantly reduced the cadmium content in the kidney. In another experiment, mice were injected i.p. with 109CdCl2 and three days later, they were injected with chelating agents every other day for 2 weeks. HBGD was the most effective on the fecal and urinary excretions of cadmium. The hepatic cadmium content was decreased after HBGD or MeOBGD injection. The injection of HBGD caused a much greater decrease in renal cadmium content than did BGD, CBGD, or MeOBGD. The results of this study indicated that the injection of HBGD to mice pretreated with cadmium can remove cadmium from the body, mainly through fecal excretion, without redistribution of cadmium to other tissues such as the brain, testes, and heart, more effectively than that of BGD, CBGD, or MeOBGD.

Animals↗

Interleukin 5 up-regulates high-affinity interleukin 2 receptor expression by human resting peripheral T cells: a comparison with the effect of interleukin 4 on B cells.

The separate regulation mechanisms of cytokines on two classes of interleukin 2 receptors (IL-2R) on human peripheral T and B cells were analyzed by a flow cytometer using a double stain with IL-2R alpha (55 kilodalton Tac) and IL-2R beta (75 kilodalton mik beta 1, mik beta 3). Although the expression of IL-2R alpha by T cells was slightly enhanced by IL-2 and IL-4, expression of the beta chain was diminished by both cytokines. IL-5 by itself did not alter the expression of either IL-2R alpha or beta, but preculturing with IL-2 for 24 h followed by IL-5 for another 24 h induced an increase in IL-2R alpha expression and in simultaneous alpha/beta chain expression. Increased numbers of high-affinity IL-2R were confirmed by 125I binding assays. On B cells, IL-4 increased alpha, beta, and simultaneous alpha/beta chain expression, but IL-4-treated B cells did not show an increased number of high-affinity IL-2R.

B-Lymphocytes↗

Complete nucleotide sequence of the gene for a surface protein antigen of Streptococcus sobrinus.

The complete nucleotide sequence of the gene for a cell surface protein antigen (SpaA) of Streptococcus sobrinus MT3791 (serotype g) was determined. The spaA gene consisted of 4,698 bp and coded for a protein of 170,202 Da. A putative signal peptide was found in the amino-terminal end of the protein. A potential promoter sequence and a putative Shine-Dalgarno sequence preceded the open reading frame. Two internal repeating amino acid sequences were present in SpaA. One repeating region, located in the amino-terminal region, was rich in alanine, and the other, located in the central region, was rich in proline. The molecular structure of SpaA was very similar to that of the surface protein antigen of Streptococcus mutans.

Amino Acid Sequence↗

Flow cytometric analysis of lipid droplet formation in cells of the human monocytic cell line, U937.

Active uptake of a free fatty acid, oleate, and its incorporation into triacylglycerol and phospholipid in the human monocytic cell line, U937, was identified using 14C-labelled oleate. Excess triacylglycerol accumulates in the form of lipid droplets in the cytoplasm. The extent of lipid droplet formation in each cell can be assessed in the absence of any staining by 90 degrees light scatter intensity, one of the basic parameters of flow cytometry.

Cell Line, Transformed↗

Mobilization of renal and hepatic cadmium by dithiocarbamates in rats.

Sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), sodium N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD), and sodium N-p-methoxybenzyl-D-glucamine dithiocarbamate (MeOBGD) were evaluated for their efficacy in the distribution and excretion of cadmium in rats exposed to cadmium. Rats were injected intraperitoneally with 109CdCl2 (1 mg Cd/kg and 74 kBq of 109Cd/one animal) and 30 min or 24 h later, they were injected with chelating agents (400 mumol/kg). At both 30 min and 24 h after treatment with cadmium, these chelating agents all significantly enhanced the biliary excretion of cadmium. At 24 h after cadmium injection, BGD and MeOBGD were the most effective on the biliary excretion of the metal. These chelating agents were effective in mobilizing cadmium from the liver at 30 min after cadmium treatment. At 24 h after cadmium treatment, BGD and MeOBGD significantly depressed cadmium content in the liver. In another experiment, rats were injected intraperitoneally with 109CdCl2 and 3 d later, they were injected with BGD, HBGD, or MeOBGD every other day for 2 weeks. The fecal excretion of cadmium was significantly increased by these chelating agents and MeOBGD was the most effective. The hepatic and renal cadmium contents were significantly decreased after BGD, HBGD or MeOBGD injection. The injection of MeOBGD to rats pretreated with cadmium was more effective than that of BGD, HBGD, or CBGD in removing cadmium from the liver. HBGD injection was more effective in decreasing the cadmium content in the kidney. The treatment with these chelating agents did not cause the redistribution of cadmium to brain, testes, and heart.

Animals↗

[A case of pregnant woman with lupus anticoagulant positive systemic lupus erythematosus complicated with intrauterine fetal death, eclampsia, and brainstem vascular damage].

A 28-year-old female patient with SLE was found to have complications from intrauterine fetal death, eclampsia, and brainstem vascular damage during pregnancy. These symptoms were associated with lupus anticoagulant (LAC). An LAC positive SLE case with accompanying cerebrovascular disease and fetal loss at the same time has rarely been reported. The first brain CT scan revealed the presence of multiple middle pons infarction. Ten days after onset, a brain MRI showed the change into hemorrhagic infarction in the same region, suggesting disseminated intravascular coagulation (DIC) caused by severe obstetric complications. Although the severity of the brain damage implied poor prognosis, her symptoms were alleviated by intensive care with a large amount of steroid therapy and active rehabilitation. LAC-positive SLE patients are apt to encounter obstetric complications in pregnancy. Therefore they must be treated by medical specialists in cooperation with gynecologists. When they also have accompanying with cerebrovascular diseases, active therapy for SLE is necessary for a good prognosis.

Adult↗

Augmentation of LDL receptor activities on lymphocytes by interleukin-2 and anti-CD3 antibody: a flow cytometric analysis.

Dormant lymphocytes are known to show little LDL receptor (LDL-R) activities. The present study was designed to determine whether or not LDL-R activities of lymphocytes from normal subjects were high enough to be measured by flow cytometry after the cells had been stimulated with recombinant interleukin-2 (IL-2) and anti-CD3 monoclonal antibody (mAb). IL-2 or anti-CD3 mAb individually provokes proliferation of lymphocytes in a serum-free medium. Proliferation rate was accelerated when the two reagents were used in combination. Stimulated cells cultured for 5 days expressed more than 85% CD3 positive, less than 0.5% CD14 positive, and less than 1.5% CD20 positive. The LDL-R activities of the cells were examined by the uptake of a fluorescence probe, DiI-labeled LDL (DiI-LDL) and analyzed by flow cytometry. Stimulated cells showed increased uptake of DiI-LDL and 84 +/- 9% were positive, whereas only 3.0 +/- 2.5% of the cells without stimulation were positive (P less than 0.001). Under the same conditions stimulated lymphocytes from a homozygous familial hypercholesterolemia (FH) patient showed little LDL-R activities; 14% of the cells were positive. Displacement assays reveal that the uptake of LDL by these cells is occurring by way of its specific pathway. These data imply the lymphocytes stimulated with the reagents used in the study might be used for detecting defects in LDL-R, perhaps defects in other genomic systems as well.

Antibodies, Monoclonal↗

Characterization of human monocytic cell line, U937, in taking up acetylated low-density lipoprotein and cholesteryl ester accumulation. A flow cytometric and HPLC study.

The uptake of LDL and acetylated LDL and the ability of cholesteryl ester accumulation by cells of a human monocytic cell line, U937, has been characterized by flow cytometric assay using a fluorescent probe, DiI, and by high-performance liquid chromatography (HPLC). The increase of mean fluorescence intensity of U937 incubated with DiI-labeled lipoproteins demonstrates that this cell line could incorporate DiI-AcLDL, as well as DiI-labeled LDL. Competition and saturation studies indicate that the manner of taking up DiI-AcLDL is receptor-mediated. While differentiated U937 incubated with 16 nM phorbol myristate acetate for 24 h took up little DiI-AcLDL, HPLC analysis confirmed that intracellular free and esterified cholesterols significantly increase in the U937 cells incubated with AcLDL or LDL. The ability of mouse peritoneal macrophage to abundantly accumulate at least five kinds of cholesteryl ester were also shown in this analysis. In contrast, in U937 cells, free fatty acids are incorporated into various substances rather than into cholesteryl esters (as revealed by HPLC analysis), so that the cholesterol in AcLDL taken up by U937 cells is not synthesized into cholesteryl esters to any great extent.

Acetylation↗

Renal osteodystrophy in patients on continuous ambulatory peritoneal dialysis.

Twelve patients on continuous ambulatory peritoneal dialysis (CAPD) were studied in order to evaluate the progression of renal osteodystrophy (ROD). All patients received doses of 0.01-0.02 microgram/kg of 1 alpha vitamin D3 (1 alpha-D3) and 0.1-0.15 g/kg of calcium carbonate for 12-18 months. Serum total protein, total calcium (Ca), creatinine, inorganic phosphate, alkaline phosphatase (ALP), and n-terminal parathyroid hormone were measured regularly. The radiological bone appearance for ROD or rickets and the height standard deviation score were compared between the outset and the end of this study. An increase of Ca values and a decrease of ALP values correlated with a suppression of hyperparathyroidism, and the hyperphosphatemia was controlled in the majority of our patients throughout this study. Two patients had ROD and rickets at the outset of this study, and all patients but one had neither ROD nor rickets at the end of this study. Growth retardation improved or remained stable in 10 patients. Our results indicate that adequate doses of 1 alpha-D3 and calcium carbonate are effective in the prevention of ROD and rickets in patients on CAPD.

Adolescent↗

Effects of three dithiocarbamates on tissue distribution and excretion of cadmium in mice.

N-Benzyl-D-glucamine dithiocarbamate (BGD), N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), and N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD) were compared for their relative efficacies in the distribution and excretion of cadmium in mice exposed to cadmium. Mice were injected intraperitoneally with 109CdCl2 (1 mg of Cd/kg and 2 microCi of 109Cd/one animal). Three days later, they were injected with chelating agents (400 mumol/kg) every other day for 2 weeks. After injections of BGD and HBGD, cadmium was excreted mainly in the feces through the bile, and the fecal excretion of cadmium by HBGD was significantly higher than that by BGD or CBGD. These chelating agents increased the urinary excretion of cadmium to a small extent. The hepatic cadmium content was decreased only after HBGD injection. Also, the injection of HBGD caused a much greater decrease in renal cadmium content than did BGD or CBGD. These chelating agents did not result in the redistribution of cadmium to the brain, testes, or heart. The growth of mice was only slightly retarded by injections of these chelating agents. The results of this study indicate that the injection of HBGD to mice pretreated with cadmium can remove cadmium from the body, mainly through fecal excretion, without redistribution of cadmium to other tissues such as the brain, testes, and heart, more effectively than BGD or CBGD.

Animals↗

Effects of several dithiocarbamates on tissue distribution and excretion of inorganic mercury in rats.

The effects of various chelating agents, sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-methylbenzyl-D-glucamine dithiocarbamate (MBGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), and N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD), which were newly synthesized, and sodium N-methyl-D-glucamine dithiocarbamate (MGD), on the distribution and excretion of inorganic mercury were compared in rats exposed to HgCl2. Rats were injected i.p. with 203HgCl2 (300 micrograms of Hg and 74 kBq of 203Hg/kg) and 30 min or 24 h later, they were injected with a dithiocarbamate (1200 mumol/kg). At 30 min after mercury administration, BGD and MBGD significantly enhanced the biliary excretion of mercury, while CBGD, MGD, and HBGD enhanced the urinary excretion of mercury to a small extent. At 24 h after mercury injection, BGD was the most effective on the biliary excretion of the metal, while MGD and HBGD significantly enhanced the urinary excretion of the metal. All of these dithiocarbamates were effective in mobilizing mercury from the kidney at 30 min after mercury treatment. At 24 h after mercury treatment, HBGD and BGD effectively depressed mercury content in the kidney. These results show that the injection of BGD and HBGD at both 30 min and 24 h after mercury treatment can much more effectively mobilize mercury from the kidney without redistribution of mercury to other tissues, such as brain, heart, and lung, when compared with injection of other chelating agents. The pattern of mobilization and excretion of mercury following treatment with each chelating agent was related to the organic/aqueous partition coefficient of each dithiocarbamate-mercury complex.

Animals↗

Pretreatment of human vascular smooth muscle cells with interleukin-1 enhances interleukin-6 production and cell proliferation (action of IL-1 on vascular smooth muscle cells).

Systemic vasculitis is an inflammatory disorder of blood vessels characterized by a perivascular mononuclear cell infiltration around the vessel and fibrinoid necrosis within vessel walls. Interleukin-1 (IL-1) is a multipotent inflammatory mediator and affects several properties of vascular cells. To determine whether IL-1 could contribute to the pathogenesis of vascular diseases, we examined the effect of IL-1 on B cell stimulatory factor-2/interleukin-6 (IL-6) production by cultured human vascular smooth muscle cells (SMC) and the proliferation of these cells. Supernatants of SMC stimulated IgM synthesis of human B cell line. SKW6-CL4 cells. This activity was increased (1.7 to 2.6-fold) when SMC were pretreated with IL-1 or calcium ionophore A23187 for 48 h, and was completely blocked by rabbit anti-human IL-6 antibodies. These IL-6 activities of the SMC supernatants were also assessed by using an IL-6 dependent murine hybridoma cell line. MH-60. BSF-2. In addition, we observed that pretreatment of SMC with IL-1 for 48 h stimulated growth of SMC during the 96 h incubations, as assessed by cell number (p less than 0.05). These results suggest that IL-1 may contribute to the pathogenesis of inflammatory and immunological vasculitis by the augmentation of IL-6 release and growth of SMC.

Calcimycin↗

Comparative effects of three dithiocarbamates on tissue distribution and excretion of cadmium in mice.

The effects of sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), and sodium N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD), which were newly synthesized, on the distribution and excretion of cadmium were compared in mice exposed to cadmium. Mice were injected with 109CdCl2 (1 mg Cd/kg and 74 KBq of 109Cd/one animal) and 30 min or 24 h later, they were injected with the dithiocarbamates (400 mumols/kg). At 30 min after treatment with cadmium, these chelating agents significantly enhanced the biliary excretion of cadmium, and HBGD and CBGD significantly increased the urinary excretion of the metal. At 24 h after cadmium injection, BGD and HBGD significantly increased the biliary excretion of cadmium and HBGD was the most effective on the biliary excretion of the metal. These chelating agents were effective in mobilizing cadmium from the liver and kidney at 30 min after cadmium treatment. HBGD showed the largest effectiveness on the depression of cadmium contents in the liver and kidney. At 24 h after cadmium treatment, only HBGD among these chelating agents significantly reduced the cadmium contents in the liver and kidney. These results show that the injection of HBGD at both 30 min and 24 h after cadmium treatment can much more effectively mobilize cadmium from the body mainly through the bile without redistribution of cadmium to other tissues, such as brain, testes, and heart, than injection of BGD and CBGD.

Animals↗

Elevated plasma levels of alpha 2-plasmin inhibitor-plasmin complex in patients with rheumatic diseases. Possible role of fibrinolytic mechanism in vasculitis.

Plasma levels of alpha 2-plasmin inhibitor (alpha 2PI) and alpha 2-plasmin inhibitor-plasmin complex (alpha 2 PIPC) were measured by sandwich enzyme-linked immunosorbent assay, using a recently developed monoclonal anti-alpha 2PI antibody, in patients with collagen diseases. Twenty patients had systemic lupus erythematosus (SLE), 4 of whom also had vasculitis, 11 patients had rheumatoid arthritis (RA), 4 of whom also had vasculitis, and 5 patients had other types of vasculitis. There was no significant difference in alpha 2PI levels between the 3 patient groups and the control groups. However, plasma levels of alpha 2PIPC in all 3 patient groups were significantly higher than those in the control group. Moreover, plasma concentrations of alpha 2PIPC in SLE patients with vasculitis were statistically significantly higher than those in SLE patients without vasculitis. These concentrations were also higher in RA patients with vasculitis than in RA patients without vasculitis, although the difference was not statistically significant. Our findings indicate that measurement of plasma alpha 2PIPC levels is useful for detecting and evaluating the severity and activity of vasculitis in patients with collagen diseases.

Adolescent↗

Expression of TLiSA1 on T cells from patients with rheumatoid arthritis and systemic lupus erythematosus.

The expression of a new activation antigen, T cell lineage specific activation antigen (TLiSA1) on peripheral blood T cells from 16 rheumatoid arthritis (RA) and 8 systemic lupus erythematosus (SLE) patients and synovial fluid T cells from RA patients was determined in the context of T cell activation. The percentages of TLiSA1 positive T cells from inactive (4.6 +/- 5.2, mean +/- SE) or active RA (19.3 +/- 8.6) or inactive (1.7 +/- 2.1) or active SLE (8.7 +/- 2.7) were significantly increased compared with that of normal controls (0.7 +/- 0.4) (P less than 0.01). All patients with vasculitis showed relatively high positive percentages. The mean fluorocytometric intensity of TLiSA1 positive T cells from RA and SLE patients was significantly higher than that from normals. Percentages of TLiSA1 positive T cells from synovial fluids (21.8 +/- 4.9%) were significantly increased compared with those from peripheral blood of the same patients, indicating the local activation of T cells in patients with RA. An increase in the expression of TLiSA1 with no increase in the expression of the very late activating antigen 1 (VLA-1) was found in peripheral blood from RA, suggesting a difference in the stage of T cell activation in RA. In RA, there was a clinical correlation with levels of TLiSA1 expression on peripheral T cells. After stimulation with PHA, TLiSA1 positive percentages were increased on Day 2 and continued to increase through 5 days of culture. The maximum expression was obtained on Day 5. An increased number of TLiSA1 positive T cells belonged to OKT8. These results suggest that there is the systemic and the local activation of T cells in RA, following antigen stimulation, or a generalized nonspecific activation of immune system that could provide a means to monitor the abnormal immunologic activity in RA.

Antigens, Differentiation, T-Lymphocyte↗

Stimulation of interleukin 6-like B-cell differentiation factor production in human adherent synovial cells by recombinant interleukin 1.

Abnormal production of immunoglobulin in the joint space is frequently observed in patients with rheumatoid arthritis (RA). We have previously demonstrated that adherent synovial cells (ASC) from patients with RA are involved in B-cell differentiation by their spontaneous production of B-cell differentiation factor (BCDF). The regulation of the production of this factor, however, has not yet been described. We investigated the effects of recombinant interleukin 1 alpha and beta (rIL-1 alpha and rIL-1 beta) on the production of BCDF in ASC. Increased production of BCDF was observed with increased rIL-1 concentration. Production of BCDF was detected 3 h after exposure of ASC to rIL-1 and increased throughout a 48-h culture. This BCDF, assayed on SKW6-CL4 cells, was found to share a common active site with interleukin 6. The effect of rIL-1 was almost neutralized by anti-IL-1 antibody and the addition of polymyxin B did not diminish the effect of rIL-1, indicating that rIL-1 itself stimulates ASC in vitro. These results suggest that IL-1 may play a regulatory role in the production of BCDF in synovial tissue.

Cell Adhesion↗