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Biomedical subjects

S Taniguchi

Publications and source records attributed to S Taniguchi.

At least 307 records · Page 17Linked to original sources

C1q-binding immunoglobulin G in MRL/l mice consists of immune complexes containing antibodies to DNA.

Previous studies have shown that the majority of C1q-binding IgG in patients with systemic lupus erythematosus (SLE) is composed of autoantibodies to the collagen-like region of C1q. Mice of the MRL/l strain are considered as a murine model of human SLE and possess autoantibodies to nuclear antigens as well as IgM and IgG rheumatoid factors (RF). This study was undertaken to characterize the C1q-binding IgG in MRL/l mice. In contrast to human SLE, C1q-binding IgG in MRL/l mice showed immunochemical characteristics of immune complexes rather than those of autoantibodies to C1q. Namely, C1q-binding IgG in MRL/l mice was large-sized upon HPLC gel filtration and abolished by digestion with pepsin or by high salt concentration, and bound to the globular region of C1q. The C1q-binding activity in MRL/l mice was absorbed by double-stranded DNA- or single-stranded DNA-cellulose. The medium-sized immune complexes containing RF have been well documented in MRL/l mice. In this study, however, mouse IgG-Sepharose failed to absorb fully C1q-binding IgG. We conclude that the majority of C1q-binding IgG in MRL/l mice consists of large-sized immune complexes containing antibodies to DNA.

Animals↗

The comparison of peak oxygen uptake between swim-bench exercise and arm stroke.

To compare maximal cardio-respiratory stress between swim-bench exercise (SB) and arm stroke (AS), peak oxygen uptake (VO2peak) was measured in six trained swimmers. The SB was performed at stroke frequency of 50.min-1. Oxygen uptake (VO2) was measured during exercise at 3-min constant exercise intensities in SB and at 4-min constant water flow rates in AS. We measured a steady-state VO2 within 3 or 4 min after the beginning of each exercise. The exercise intensity or the water flow rate was increased by 14.7 W or by 0.05 m.s-1, respectively, until a levelling-off of VO2 was observed. The VO2 was measured by the Douglas bag method. Heart rate (HR) and blood lactate concentration ([la-]b) were determined at the exercise intensity and the water flow rate at which VO2peak was obtained. At submaximal levels, VO2 increased in proportion to exercise intensity for SB and to the water flow rate for AS. A levelling-off of VO2 was observed in all subjects for both kinds of exercise. The VO2peak during SB [2.13 (SD 0.25)1.min-1] was significantly lower than that during AS [2.72 (SD 0.39)1.min-1] and corresponded to 78.9 (SD 7.0)% of AS VO2peak. Maximal HR during SB was also significantly lower than that during AS. No significant differences between SB and AS were found for either pulmonary ventilation or [la-]b. The peak exercise duration in SB [2.4 (SD 0.5) min] was significantly shorter than that in As [3.6 (SD 0.5) min]. These results would suggest that even though both kinds of exercise use the muscles of the upper body, active muscle groups involved during SB are different and/or smaller, and maximal stress on the cardio-respiratory system is lower when compared to AS.

Adult↗

Left atrial plication combined with mitral valve surgery in patients with a giant left atrium.

The benefits of performing left atrial plication during mitral valve surgery for patients with a giant left atrium were evaluated by analyzing the short- and long-term surgical results and changes in the left atrial dimension (LAD) and respiratory function of 30 patients. Of the 30 patients, 2 (7%) died of multiple organ failure on postoperative days 26 and 117, but no other deaths occurred during the mean follow-up of 5.9 +/- 2.1 years. Valve thrombosis was observed in one patient and cerebral complications with no residual deficit were observed in two patients, with a 9-year event-free rate of 87 +/- 7%. The LAD decreased significantly from 69.0 +/- 8.5 mm to 53.7 +/- 9.1 mm (P < 0.01) shortly after surgery, and this decreased was maintained even 5 years after surgery (53.3 +/- 11.4 mm). The cardiothoracic ratio decreased from 74.8 +/- 8.3% to 62.8 +/- 9.0% (P < 0.01) and the vital capacity of the lungs increased from 71.1 +/- 18.0% to 82.9 +/- 22.2% (P < 0.01). Thus, we conclude that performing left atrial plication during mitral valve surgery is safe and effective for patients with giant left atrium.

Adult↗

Activation of the basolateral Cl- conductance by cAMP in rabbit renal proximal tubule S3 segments.

The regulatory mechanism of basolateral Cl- conductance in rabbit renal proximal tubule S3 segments was investigated with conventional and Cl- sensitive microelectrodes. After the basolateral Cl-/HCO3- exchanger was blocked by 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) we increased the bath K+ concentration from 5 mmol/l to 20 mmol/l, which depolarized the cells and thereby increased intracellular Cl- activity ([Cl-]i). This [Cl-]i response was enhanced by +63% in the presence of forskolin (20 mumol/l), by +40% in the presence of dibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP) (1 mmol/l) and by +44% in the presence of parathyroid hormone (PTH, 10 nmol/l), whereas it was inhibited by a Cl- channel blocker, indanyl-oxyacetic acid (IAA-94, 0.3 mmol/l). In addition, forskolin, PTH and chlorophenylthio-cAMP enhanced the electrogenic response to removal of bath Cl- after the blockade of K+ conductance, and this activation was also sensitive to IAA-94. On the other hand, 2 mumol/l ionomycin and 0.5 mumol/l phorbol myristate failed to activate the [Cl-]i response to elevation of bath K+ concentration and the electrogenic response to Cl- removal, and ionomycin had no effect even in the absence of DIDS. These results indicate that this basolateral Cl- conductance can be activated by cAMP, while neither the increase in cytosolic Ca2+ nor the activation of protein kinase C has direct effects on this conductance.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Enhancement of prostacyclin production in cultured bovine aortic endothelial cells by oxidized glycated low-density lipoprotein.

Oxidized low-density lipoprotein (oLDL) is implicated in the pathogenesis of atherosclerosis. The serum concentration of glycated LDL (gLDL) is increased in diabetics, and it is possible that oxidative modification of gLDL contributes to the increased incidence of atherosclerosis associated with diabetes. The mechanism and effect on prostacyclin (PGI2) production by cultured bovine aortic endothelial cells of oxidized glycated LDL (ogLDL) prepared in vitro have now been examined. Glycation of LDL was performed by incubating LDL with 20 mM glucose for 3 days. ogLDL was then prepared by incubation of gLDL with 1 microM CuSO4 for 12 h. Both the electrophoretic mobility and the thiobarbituric acid reactive substance content of ogLDL were greater than those of native LDL (nLDL) or gLDL. Binding, cell-association, and degradation of ogLDL in endothelial cells were significantly greater than those of nLDL and gLDL. The stimulatory effect of ogLDL on PGI2 production was significantly greater than that of nLDL or gLDL; this effect was dose dependent. Both cell-association and the stimulatory effect on PGI2 production of oLDL were dependent on the extent of oxidation in a biphasic manner. Endothelial cells thus appear to protect against atherosclerosis by removing atherogenic lipoproteins and by producing PGI2.

Animals↗

Metabolism of oxidized glycated low-density lipoprotein in cultured bovine aortic endothelial cells.

The serum concentration of glycated low-density lipoprotein (gLDL) is increased in individuals with diabetes mellitus, which may be a contributing factor to the increased incidence of atherosclerosis in this population. Given the importance of oxidized LDL (oLDL) in atherosclerosis and that vascular endothelial cells express receptors for oLDL, oxidized glycated LDL (ogLDL) was prepared in vitro and its binding and degradation by cultured bovine aortic endothelial cells were examined. Glycation of native LDL (nLDL) isolated from normal human subjects was performed by incubation with 20 mM glucose at 37 degrees C for 3 days, and ogLDL was prepared by oxidation of gLDL with 1 microM CuSO4 at 37 degrees C for 12 hours. The electrophoretic mobility and thiobarbituric acid reactive substance (TBARS) value of ogLDL were greater than those of nLDL and gLDL. Both binding and degradation of ogLDL by cultured endothelial cells also were significantly greater than for nLDL and gLDL. Degradation of nLDL by endothelial cells was completely inhibited by ogLDL, whereas degradation of acetylated LDL was not inhibited by nLDL or ogLDL. Thus, the binding and degradation of ogLDL by endothelial cells do not appear to be mediated by the scavenger receptor. Although the exact mechanism is not clear, it appears that vascular endothelial cells may play a protective role against atherosclerosis by removing potential atherogenic lipoproteins.

Animals↗

Differential cell- and immuno-biological properties of murine B16-F1 and F10 melanomas: oncogene c-fos expression, sensitivity to LAK cells and/or IL-2, and components of gangliosides.

Differential cell- and immuno-biological properties of two murine melanoma B16 variants, B16-F1 and F10, were investigated. Studies focused on the expression of proto-oncogene c-fos, sensitivities to LAK cells and/or IL-2, and modulation of the expression of ganglioside components after treatment with IL-2. Proto-oncogene c-fos was found to be highly expressed in F10 lines by an in situ hybridization technique and also in F10 lung metastatic nests by immunofluorescent staining with anti-c-fos antibody. F1 melanomas were more sensitive to local injection of IL-2. F10 melanomas hardly responded to IL-2 treatment, but successive injections of a combination of LAK cells and IL-2 did cause prolongation of survival rates, even of F10 melanoma-burdened mice. A major component of gangliosides of both F1 and F10 melanomas was GM3. Production of GM3 in F10 melanomas treated with IL-2 for 4 days increased, and, if the treatment was continued for 7 days, minor components of gangliosides, such as GM2, GM1, and GD1a, appeared only in F1 melanomas, while the increase of production of GM3 disappeared in both melanomas. These experimental results may provide clues for additional mechanisms which allow these two murine melanoma variants to show different implantation and metastasis rates.

Animals↗

Effects of cyclosporin and ultraviolet radiation on growth and ornithine decarboxylase activity in cultured human epidermal keratinocytes.

Both cyclosporin (CyA) and ultraviolet radiation are effective in the treatment of psoriasis, but their precise mechanisms of action are uncertain. We investigated their effects on ornithine decarboxylase (ODC) activity, ODC gene expression, and cellular proliferation stimulated by epidermal growth factor (EGF), in cultured normal human epidermal keratinocytes. CyA (5 micrograms/ml) inhibited ODC activity, ODC mRNA level, and cell growth induced by 50 ng/ml EGF. Ultraviolet B (10 mJ/cm2) irradiation suppressed the induction of ODC, ODC mRNA, and cell proliferation stimulated by EGF, but ultraviolet A (0-15 J/cm2) irradiation inhibited neither EGF-stimulated ODC activity nor cell proliferation. These findings indicate that reduction of ODC activity in CyA- or ultraviolet B-treated human keratinocytes may contribute to the antiproliferative mechanism of these agents. These results also suggest that the regulation of ODC activity by ultraviolet B and A irradiation may be mediated by different signal transduction pathways.

Cell Division↗

Subcorneal pustular dermatosis in a patient with hyperthyroidism.

A case of subcorneal pustular dermatosis (SPD) is reported in a 48-year-old man with a 2-year history of hyperthyroidism (Graves' disease). SPD has been reported in association with IgA monoclonal gammopathy, but to our knowledge it has not been associated with hyperthyroidism. The coexistence of hyperthyroidism and SPD suggests that immunologic factors may play a role in the pathogenesis of SPD.

Biopsy↗

Free bile acids inhibit IgE production by mouse spleen lymphocytes stimulated by lipopolysaccharide and interleukins.

The interaction of IL-4, IL-5, and free bile acids with the immunoglobulin production by mouse spleen lymphocytes was studied to examine their immunoregulatory activity. In the absence of lipopolysaccharide (LPS), IL-4 enhanced the IgE and IgG production significantly and the IgA production weakly, but not the IgM production. On the other hand, IL-5 had an inhibitory tendency on the IgE and IgA production, though not significantly. In the presence of LPS, both IL-4 and IL-5 significantly enhanced the IgE production by mouse splenic lymphocytes. When the lymphocytes were cultured with the physiological concentration of free bile acids (10 microM) and LPS for 3 days, chenodeoxycholic acid inhibited the IgE production, but cholic and deoxycholic acids did not. In the presence of IL-4 or IL-5, these bile acids cancelled the stimulatory effects of interleukins and rather significantly inhibited the IgE production. These results suggest that these free bile acids act as an anti-allergic agent.

Animals↗

Impaired feedback inhibition of insulin secretion by hyperinsulinemia in patients with insulinoma.

By means of the euglycemic three step hyperinsulinemic clamp technique, suppression of endogenous C-peptide secretion by exogenous insulin infusion was evaluated in patients with insulinoma (n = 8) and healthy controls (n = 20). Euglycemic hyperinsulinemic clamp studies were performed with an artificial pancreas (STG-22 NIKKISO, Tokyo, Japan). Insulin (Actrapid human insulin) was infused at the rate of 1.12, 3, and 10 mU/kg/min. Plasma glucose levels were clamped at 80 mg/dl, and high insulin levels were maintained in all subjects (833 +/- 78 microU/ml at the rate of 10 mU/kg/min insulin infusion). During the clamp studies, plasma C-peptide levels in normal subjects declined from 2.0 +/- 0.2 to 0.9 +/- 0.2 ng/ml, indicating suppression of endogenous insulin secretion by exogenous insulin infusion. In patients with insulinoma, plasma C-peptide levels were 3.1 +/- 1.6 ng/ml in the basal state, and were not suppressed even during exogenous hyperinsulinemia. We concluded that the feedback inhibition of insulin secretion by exogenous insulin infusion is attenuated in patients with insulinoma, and that the hyperinsulinemic clamp technique may be a useful method for the diagnosis of insulinoma.

Adult↗

Development of hypercalcemic crisis in a Graves' hyperthyroid patient associated with central diabetes insipidus.

A 26-year-old man with Graves' hyperthyroidism associated with central diabetes insipidus (DI), initially showed hypercalcemic crisis. Initially, very low serum levels of intact parathyroid hormone (PTH) and 1,25-dihydroxy vitamin D3 and a moderate rise of serum C-terminal PTH related protein (C-PTHrP) were observed which strongly suggested a humoral hypercalcemia of malignancy due to PTHrP. However, the serum C-PTHrP level later became normal. Mild hyperprolactinemia, no responses of growth hormone (GH) to insulin-induced hypoglycemia despite a normal growth hormone releasing hormone (GRH) test and mild thickening of the pituitary stalk on magnetic resonance imaging were observed. Thus, an autoimmune nature of his central DI is considered; it is noteworthy that the serum C-PTHrP level may be elevated by renal failure in patients with hypercalcemia due to causes other than PTHrP.

Acute Disease↗

The prozone phenomenon in secondary syphilis.

We describe a 37-year-old woman with secondary syphilis, in whom the prozone phenomenon (false-negative test in undiluted specimens) occurred. The patient had been maintained on cyclosporine and prednisolone after renal transplantation. B-cell dysfunction induced by continuous immunosuppression may lead to higher non-treponemal serological titers. Non-treponemal testing should be repeated using serum dilutions to prevent missing the diagnosis of syphilis.

Adult↗