Suppression of proteinuria and prolongation of survival in MRL-lpr/lpr mice treated with sulphasalazine.
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Animals↗
Biomedical subjects
C Y Tsai
Publications and source records attributed to C Y Tsai.
Defective spontaneous and bacterial lipopolysaccharide-stimulated production of interleukin-1 receptor antagonist by polymorphonuclear neutrophils of patients with active systemic lupus erythematosus.
Interleukin-1 receptor antagonist (IL-1ra) binds competitively to IL-1 receptors but does not transduce the signal which blocks the biological activities induced by IL-1. In this study, polymorphonuclear neutrophils (PMN) and mononuclear cells (MNC) from the patients with active systemic lupus erythematosus (SLE) (n = 11), inactive SLE (n = 13) and normal individuals (n = 13) were compared for the IL-1ra producing capacity of these cells. PMN and MNC at a concentration of 1 x 10(6) cells/ml were incubated with medium alone (spontaneous) or stimulated with lipopolysaccharide (LPS, 100 ng/ml) for 24 h. The IL-1ra concentration in the supernatants was quantified by ELISA method. Both spontaneous and LPS-stimulated production of IL-1ra by PMN, but not by MNC, of active SLE were significantly lower than that of inactive SLE or normal groups. Prednisolone (1 and 5 micrograms/ml) did not change the production of IL-1ra by normal PMN either spontaneously or LPS-stimulation in in vitro study. Moreover, the IL-1ra producing capacity of PMN in seven active SLE on admission and after intensive immunosuppressive treatment was measured. These results suggest that the defective IL-1ra production by SLE-PMN is relevant to disease activity and may be regarded as a new indicator of disease activity in patients with active SLE.
Adolescent↗
Abnormal splenic and thymic IL-4 and TNF-alpha expression in MRL-lpr/lpr mice.
The MRL-lpr/lpr and MRL-(++) mice were studied for the expression of cytokines in the spleen, lymph node, thymus, kidney and brain through the reverse transcription-polymerase chain reaction (RT-PCR). The frequencies of IL-4 and TNF-alpha expression in the thymus and spleen were significantly higher in MRL-lpr/lpr mice than in MRL-(++) mice from the age of 17 to 32 weeks. More importantly, IL-4 transcript was demonstrated in the early rather than in the terminal stage of the lupus disease. At the 20th week, MRL-lpr/lpr mice with active disease exhibited higher concentrations of IL-1 alpha, IL-6 and TNF-alpha in serum than MRL-(++) mice. Interestingly, in MRL-lpr/lpr but not MRL-(++) mice, the IL-6 concentration in cultured supernatants of the thymic cells was significantly higher than that of the splenic or lymph node cells. On the other hand, IL-6 and IL-1 beta were expressed in the brain and kidney of MRL-lpr/lpr mice but not of MRL-(++) mice. Cultured MRL-lpr/lpr mesangial cells could also express IL-6 but to a lesser extent. These results suggest that the abnormal splenic and thymic IL-4 and TNF-alpha expression may predispose the development of autoimmune reactions. The expression of IL-1 beta and IL-6 in the brain and kidney may be implicated in the damage of these two organs in MRL-lpr/lpr mice.
Animals↗
The physiologic and pathologic roles of Tamm-Horsfall glycoprotein in urinary system.
Tamm-Horsfall glycoprotein (THG), a unique renal glycoprotein, is synthesized exclusively by the epithelial cells of the thick ascending loop of Henle and early segment of distal convoluted tubules. The protein is the primary constituent of urinary hyaline cast. The aggregation and gel formation of THG in response to increasing concentrations of electrolytes and low pH within physiologic ranges may affect the permeability of water in this segment. The dual effect of THG on mononuclear cells renders the molecule to become a potent immunomodulator. The cytokine-binding activity of THG lets the kidney an important tissue for cytokine catabolism. The aggregation characteristics of THG also plays a role in pathologic states and leads to the persistence of interstitial deposits in several tubulointerstitial diseases. The induction of immune responses to this protein, including urinary tract infection, reflux nephropathy chronic active hepatic damage, elicites immune complex tubulointerstitial nephritis. It is expected that the detection of THG or its antibodies may aid in the diagnosis of renal tubular disorders.
Adjuvants, Immunologic↗
Anti-dsDNA antibodies cross-react with ribosomal P proteins expressed on the surface of glomerular mesangial cells to exert a cytostatic effect.
Affinity-purified human polyclonal anti-double-stranded DNA antibodies (anti-dsDNA) exerted a cytostatic effect towards human and rat glomerular mesangial cells (MC). In order to identify the cognate antigens for anti-dsDNA on the surface of MC, we used these autoantibodies to probe a human renal lambda gt11 cDNA expression library. Two cDNA clones encoding the cognate proteins for the autoantibodies were isolated. Sequencing analysis of the two cDNA showed that they had 98.6% homology with the gene of the P0 and 99.2% homology with the gene of the P1 human acidic ribosomal phosphoproteins (P protein). Two galactosidase fusion proteins (125,000 and 150,000 MW) derived from the two cDNA inserts expressed in lysogenic Escherichia coli Y1089 could react with the original screening antibodies in an immunoblotting analysis. After transformation and expression of the full-length P1 clone in prokaryotic cells, the purified P1 protein was able to react with anti-dsDNA. In a cross-inhibition experiment, the dsDNA binding activity of anti-dsDNA was inhibited by a synthetic polypeptide corresponding to the carboxyl-terminal 20 amino acids of P protein and purified P1 protein in a dose-dependent manner, but this was less potent than the inhibition caused by calf thymus dsDNA. By use of well-defined systemic lupus erythematosus (SLE) sera, we found only sera containing a high titre of anti-dsDNA activity (> 300 IU/ml) reacted with P1 of rat MC lysate. Furthermore, the 38,000 and 19,000 MW macromolecules were proved to be the cognate antigens for anti-dsDNA expression on the surface of the MC, by Western blot of the MC plasma membrane lysates. These results suggest that anti-dsDNA may cross-react with ribosomal P proteins expressed on the surface of the MC and exert cytostasis towards these cells.
Animals↗
Scleroderma associated with Castleman's disease.
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Castleman Disease↗
Dialysis-related amyloidosis and acquired renal cystic disease with renal cell carcinoma in uremia.
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Amyloidosis↗
Cerebrospinal fluid interleukin-6, prostaglandin E2 and autoantibodies in patients with neuropsychiatric systemic lupus erythematosus and central nervous system infections.
Cerebrospinal fluid (CSF) from patients with a variety of central nervous system (CNS) disorders was assayed for cytokines, prostaglandins, and autoantibodies. CSF interleukin-6 (IL-6) in patients with CNS infection (374.24 +/- 92.61 pg/mL) and neuropsychiatric systemic lupus erythematosus (NP-SLE) (71.40 +/- 5.89 pg/mL) were significantly higher than in patients with CNS inflammation (33.92 +/- 29.36 pg/mL) or controls (non-inflammatory CNS diseases) (4.35 +/- 3.00 pg/mL). Interleukin-1 beta, interferon alpha, and tumor necrosis factor alpha were undetectable in these samples: CSF prostaglandin E2 (PGE2) also exhibited similar patterns as IL-6. CSF immunoglobulin G (IgG) in patients with NP-SLE (8.84 +/- 1.80 mg/dL) was much higher than in patients with CNS infection (4.65 +/- 3.09 mg/dL), CNS inflammation (2.54 +/- 1.24 mg/dL), or controls (2.11 +/- 1.03 mg/dL). CSF autoantibodies against calf thymus antigens were present in patients with NP-SLE but not in patients with CNS infection as demonstrated by immunoblot. These results suggest that high IL-6 and PGE2 in CSF favors the diagnosis of CNS infection, while modestly elevated IL-6, high IgG, and autoantibodies against calf thymus antigens in CSF are the features of NP-SLE.
Autoantibodies↗
Abdominal wall hernia complicating continuous ambulatory peritoneal dialysis.
Continuous ambulatory peritoneal dialysis (CAPD) is a well-established treatment modality for end-stage renal disease. Abdominal wall hernia is not uncommon in patients on CAPD. Two factors are responsible for the occurrence of these hernias: anatomically weak sites and increased intraperitoneal pressure by the dialysate. Abdominal wall hernia was reviewed in 44 patients on CAPD from 1987 through 1991. Eight abdominal hernias (5 inguinal, 2 incisional and 1 umbilical) were found during CAPD treatment (18.18%). Surgical treatment was applied in 6 symptomatic hernias (5 inguinal and 1 incisional). After surgery, 5 patients returned to CAPD without recurrence and the remaining one died of strangulated incisional hernia. Our series shows that: (1) a detailed examination of the preexisting hernia and repair prior to CAPD treatment are suggested. (2) symptomatic abdominal wall hernia should be evaluated carefully and treated promptly. (3) awareness of the complication of these hernias can reduce the morbidity and mortality.
Adult↗
[Postpartum adjustment of women who were home during the "traditional Chinese one month postpartum period of confinement" and those who were in maternity care centers].
The purpose of this study was to explore the difference in postpartum adjustment between women who were at home for there "doing the month" and those who stayed in a maternity care center. A repeated measures design was conducted, with data collected at 1 and 4 weeks postpartum. A total of 120 postpartum women participated in this study. Data were analyzed by factor analysis to determine the relationships within categories of postpartum strssors and depression. Then, the data were analyzed by 2 x 2 repeated measure MANOVA to determine the variations among groups and time. The results indicated that women who were in maternity centers for the "doing the month" perceived significantly higher stress than did the home group, and that women perceived higher stress at 4 weeks postpartum than at 1 week postpartum. Factor analysis of the data defined four categories of postpartum stress. It was found that women at maternity care centers perceived significantly higher stress from factors named, "stress from lacking of support system" and "stress from identifying maternal role". In addition, women doing the month at maternity care centers showed significantly higher depression level than women doing the month at home. However, there is no significant difference in postpartum stress and postpartum depression between time 1 (1 week postpartum) and time 2 (4 weeks postpartum).
Adaptation, Psychological↗
The elevation of plasma DNA in patients with systemic lupus erythematosus is attributable to increased DNA release and defective DNA binding of mononuclear cells.
BACKGROUND: Although immunoprecipitable DNA has been found in a subgroup of patients with systemic lupus erythematosus (SLE) exhibiting systemic vasculitis and/or central nervous system involvement, the mechanism for elevated plasma DNA in these patients is poorly understood. METHODS: The plasma DNA concentrations and reactivity of serum and lymphocytes to six species of double-stranded DNA from calf thymus, human placenta, Escherichia coli, Micrococcus lysodeikticus, Clostridium perfringens and poly (dG.dC). poly (dG.dC) were measured in twenty-seven patients with active SLE. To understand the mechanism of increased plasma DNA in SLE, the DNA binding and release of the mononuclear cells were examined. RESULTS: Compared with the controls, the incidence of the presence of plasma DNA was markedly increased in SLE (59.3% in SLE vs. 7.4% in controls) as detected by counterimmunoelectrophoresis. Except for DNA from Clostridium perfringens, the reactivity of lupus sera to various DNA samples was significantly higher than that of the controls. The reactivity of lymphocytes to 6 species of DNA (as defined by 3H-thymidine incorporation of the cells) was also higher in SLE patients. In DNA binding and releasing experiments, patients with SLE were found to have decreased 3H-DNA binding activity (0.169 +/- 0.018 micrograms/2 x 10(6) cells in SLE vs. 0.283 +/- 0.02 micrograms/2 x 10(6) cells in controls, p = 0.001) but to have increased spontaneous release of DNA (1,465 +/- 412 cpm in SLE vs. 630 +/- 179 cpm in controls, p = 0.0173) in mononuclear cells. CONCLUSIONS: The results suggest that some subsets of lymphocytes can be sensitized by different DNA samples in vivo to increase endogenous DNA release from mononuclear cells, which in addition to decreased DNA clearance as has been previously reported, may be responsible for the elevation of plasma DNA in patients with SLE.
Adult↗
Small cell carcinoma of the lung in a patient with rheumatoid arthritis: a case report.
We describe an occurrence of small cell carcinoma of the lung in a 37-year-old woman with rheumatoid arthritis who did not receive any kind of cytotoxic agents for the rheumatic condition. There seemed to have no predisposing factor for the development of malignancy. The diagnosis of small cell carcinoma was based on repeated hemoptysis and cytologic finding of a rapidly growing mass over the forehead. The patient responded dramatically to chemotherapy with rapid resolution of forehead mass, relief of arthritis in the hands, and decrease of serum rheumatoid factor from 4800U/ml to 1200U/ml. This appeared to be the first report of small cell carcinoma of the lung developing in a patient with rheumatoid arthritis.
Adult↗
Subarachnoid glioependymal cyst: a case report.
A case of subarachnoid glioependymal cyst in a newborn baby is reported. An intracranial cystic lesion was found at 32 weeks of gestation by ultrasonography. The infant was born with an enlarged head and impaired auditory evoked potential (AEP). Computed tomography and magnetic resonance imaging revealed a large homogeneous cystic lesion over the left cerebral convexity with displacement of the left hemisphere to the right. Craniotomy was performed, with removal of the cystic wall and insertion of a cystoperitoneal shunt. Postoperatively, improvement was noted on clinical examination and ultrasonography. Previously, only one such case, treated perinatally, has been reported.
Arachnoid Cysts↗
Prostaglandin E2 suppresses phytohemagglutinin-induced immune responses of normal human mononuclear cells by decreasing intracellular glutathione generation, but not due to increased DNA strand breaks or apoptosis.
Prostaglandin E2 (PGE2) at concentrations more than 1 x 10(-8) M markedly suppressed the cell proliferation and release of soluble molecules of interleukin-2 receptor (sIL-2R), CD4 (sCD4) and CD8 (sCD8) from phytohemagglutinin (PHA)-stimulated normal human mononuclear cells (MNC) in a dose-related manner. To further elucidate the subcellular mechanism of the inhibitory effect of PGE2 on PHA-stimulated MNC, intracellular concentration of glutathione (GSH) in PHA-stimulated MNC was sequentially measured from day 1 to day 3 by enzymic method. Furthermore, the effect of PGE2 on nuclear DNA including DNA strand breaks in alkali treatment and DNA fragmentation (apoptosis) of PHA-stimulated MNC were also measured. We found intracellular GSH levels were significantly decreased in the early stage of lymphocyte activation (day 1), but no evidence of increased DNA strand breaks or apoptotic process appeared in 3-day culture. In addition, butathione sulfoximine (a specific GSH inhibitor) and dibutyryl cyclic AMP also exhibited both proliferation inhibition and GSH-decreasing effects on PHA-stimulated MNC as well as PGE2. These results suggest that the immunosuppressive effect of PGE2 is mediated by the decreased generation of intracellular GSH, but not by the increased DNA strand breaks or apoptotic mechanism in the cells.
Antimetabolites↗
Apoplectic optochiasmal syndrome due to intrinsic cavernous hemangioma. Case report.
A 42-year-old man suffered from acute evolving visual loss after drinking alcohol. Consecutive visual field changes suggested a mass within the left optic nerve extending its compression across the chiasm and encroaching on the left optic tract. Computed tomography scanning and magnetic resonance imaging confirmed the presence of an overt hemorrhage, a real apoplectic event of cavernous hemangioma. Cavernous hemangiomas located within the intracranial optic nerve are few. Occult hemorrhage within the confines of the intrinsic vascular tumor resulted in acute visual changes in most reported cases. Overt hemorrhage with blood extravasation beyond the original confines of the intrinsic optochiasmal tumor are rarely reported in the literature. Herein, we report one such case. The clinical course and the predisposing factors are also discussed.
Adult↗
Increased spontaneous release of cytidine deaminase by polymorphonuclear neutrophils of patients with active systemic lupus erythematosus.
Cytidine deaminase activity (CD) in the neutrophil culture supernatants (PMN SUP) of 27 patients with systemic lupus erythematosus (SLE) was measured using a spectrophotometric method. Compared with the controls (5.449 +/- 1.358 U/5 x 10(6) PMN), the CD activity in the spontaneous culture supernatants of PMN was significantly increased in active (10.003 +/- 2.637 U/5 x 10(6) PMN) but not in inactive (5.358 +/- 1.624 U/5 x 10(6) PMN) SLE. However, after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 x 10(-7) M), the ratio of enzyme activity between stimulated and spontaneous PMN supernatants was decreased in active SLE (0.794 +/- 0.178) compared with normal controls (1.300 +/- 0.225). In contrast, the enzyme activity in the cytoplasm of either stimulated or non-stimulated PMN was not different among these three groups. These results suggest that CD of PMN is releasable and can be enhanced by chemotactic factor stimulation in normal PMN. The increased spontaneous release of CD by active SLE PMN is one of the indicators for the disease activity in these patients.
Adult↗
Effect of antibodies to double stranded DNA, purified from serum samples of patients with active systemic lupus erythematosus, on the glomerular mesangial cells.
Polyclonal antibodies to double stranded DNA (dsDNA) purified from pooled serum samples of patients with systemic lupus erythematosus (SLE) exerted cytotoxic effects on cultured rat mesangial cells. At concentrations from 5 to 150 IU/ml, antibodies to dsDNA inhibited the incorporation of thymidine labelled with 3H into rat mesangial cells in a dose response manner after three days of culture. In contrast, normal human IgG (1 mg/ml), heat aggregated human IgG (1 mg/ml), N-formyl-methionyl-leucyl-phenylalanine (1 x 10(-7) mol/l), tumour necrosis factor alpha (16 U/ml), lipopolysaccharides (1 microgram/ml), 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA) (20 ng/ml), interleukin 1 beta (10 U/ml), and 20% v/v phytohaemagglutinin stimulated mononuclear cell supernatant showed no significant effect on these cells. Anticardiolipin antibody, another autoantibody purified from the serum of patients with SLE, also inhibited the proliferation of rat mesangial cells but to a lesser extent. In the presence of antibodies to dsDNA (100 IU/ml), the mesangial cells became spherical and clustered together, which was very different from the original stellate appearance. These autoantibodies also depolarised the membrane potential of mesangial cells. Antibodies to dsDNA decreased the syntheses of prostaglandin E2, 6-keto-prostaglandin F1 alpha and thromboxane B2 by mesangial cells. In an in vivo study, the antibodies to dsDNA showed a strong affinity for the glomeruli when intravenously injected into rats. These results suggest that the nephrotropic antibodies to dsDNA can directly damage the glomerular mesangial cells in addition to the formation of immune complexes with DNA which may cause kidney inflammation and tissue destruction.
6-Ketoprostaglandin F1 alpha↗
Increased excretion of soluble interleukin 2 receptors and free light chain immunoglobulins in the urine of patients with active lupus nephritis.
Samples of protein from the urine of 23 patients with lupus nephropathy and 15 patients with proteinuria who did not have systemic lupus erythematosus (SLE) were studied for the presence of cytokines, soluble interleukin 2 receptors (sIL-2R), and free light chain immunoglobulins. The patients with lupus nephropathy were divided into two groups with active (nephritis) and inactive inflammation (nephrosis) based on the results of the analysis of urine samples and renal histology. The crude urine proteins (5 mg/ml) after precipitation by 80% ammonium sulphate from 14 patients with lupus nephritis contained higher concentrations of sIL-2R (4.88 (SEM 1.27 ng/ml) than those from nine patients with nephrosis (1.11 (0.52) ng/ml) or 15 patients without SLE (1.31 (0.87) ng/ml). The concentration of sIL-2R in protein from urine samples was not correlated with the concentration in plasma and was inversely correlated with the excretion of protein in urine over 24 hours in patients with SLE. It is suggested that, in addition to leakage from the circulation, the local production of sIL-2R by inflamed kidneys is possible. The crude proteins in urine were further fractionated by gel filtration on Sephacryl S-200. Arbitrarily, four fractions could be obtained from urine from patients with SLE but only three fractions were found in the urine of patients without SLE. Fraction IV derived from patients with nephritis or nephrosis augmented the pokeweed mitogen induced [3H]thymidine uptake of mononuclear cells. In addition, the positive rates of free kappa (kappa) (35.7%) and lambda (lambda) (42.9%) chains in proteins in urine from nephritic patients were higher than those in the other two groups. These results suggest that the severity of inflammation in the kidneys of patients with lupus can be reflected by the increased excretion of sIL-2R, free light chain immunoglobulins, and cytokine-like molecules in urine.
Adolescent↗