Pseudogout attack associated with chronic thyroiditis and Sjögren's syndrome.

A 66-year-old woman, diagnosed with chronic thyroiditis at age 63, presented with anorexia and fatigue. Therapy for the chronic thyroiditis consisted of levothyroxine sodium (100 microg/day). Her symptoms were attributed to the insufficient supply of levothyroxine sodium. Following a dosage increase to 150 microg/day, she suffered from an acute attack of pseudogout. Clinical features were complicated by Sjögren's syndrome, which appeared after treatment onset. Pseudogout was effectively treated by colchicine after administration of diclofenac sodium failed to alleviate the symptoms. Pseudogout is a recognized complication of thyroid replacement therapy, but association with Sjögren's syndrome has not been previously reported.

[Studies on the conditions of blood sampling and storage for the liposome-based CH50 assay].

The CH50 values in the serum and plasma, especially those from chronic hepatitis caused by hepatitis C virus (HCV), are strongly affected and reduced through a process known as cold activation. We attempted to optimize the conditions of blood sampling and storage for the CH50 assay with a recently developed liposome-based assay kit. The bloods were obtained from HCV hepatitis patients as well as healthy donors. Regardless of the temperature (room temperature, 4 degrees C or 37 degrees C) at which samples were kept until the assay, higher values were always obtained in the serum than in the plasma. The plasma samples could either be heparinized or given any of the other anticoagulants, EDTA-2K and sodium citrate, at the time of sampling. We also attempted to optimize the temperature at which the fresh specimens were left during the period from sampling to assay and the temperatures to freeze them for storage and to thaw for assays. In the assays immediately after sampling, higher values were obtained when the specimens were left at 37 degrees C than at room temperature or 4 degrees C. To store at -80 degrees C rather than at -20 degrees C and to thaw rapidly at 37 degrees C rather than slowly at room temperature were found to be advantageous.

Subclinical Fabry's disease occurring in the context of IgA nephropathy.

A 28-year-old male patient with both IgA nephropathy and an unusual case of Fabry's disease has been followed for 10 years. Diagnosis of both these diseases was made by histological examination of renal biopsy tissues and the enzyme activities of alpha-galactosidase A. Serial biopsies revealed the hithertofore unrecognized process of glomerular glycolipid accumulation peculiar to Fabry's disease at the initial stages of the disease. Physical examinations and routine laboratory analyses failed to show significant signs of Fabry's disease throughout the 10-year period. While alpha-galactosidase A activity is markedly decreased in the plasma of this patient as in classical Fabry hemizygotes, the activity in leukocytes and culture fibroblasts showed a considerable residual activity. Fabry's disease associated with IgA nephropathy apparently is extremely rare, and the present subclinical case is unique in that the early stages of substrate accumulation are demonstrable.

Effects of interferon gamma on cultured synovial cells from patients with rheumatoid arthritis: inhibition of cell growth, prostaglandin E2, and collagenase release.

The effects of recombinant interferon gamma (rIFN gamma) on the in vitro growth of adherent synovial fibroblast-like cells from patients with rheumatoid arthritis (RA) and also on the release of prostaglandin E2 and collagenase from these cells stimulated with recombinant interleukin-1 beta (rIL-1 beta) were investigated. The growth of adherent synovial cells from six of nine samples, determined by [3H]thymidine incorporation, was inhibited by rIFN gamma in a manner dependent on dose. The release of prostaglandin E2 and collagenase from adherent synovial cells stimulated with rIL-1 beta was also suppressed by rIFN gamma in all samples tested, though the basal release of these inflammatory mediators was little influenced. No apparent correlation between inhibition of proliferation by rIFN gamma and either inhibition by rIFN gamma of rIL-1 beta stimulated prostaglandin E2 release or the endogenous synthesis of prostaglandins was found.

Inhibition of phagocyte chemotaxis by uteroglobin, an inhibitor of blastocyst rejection.

Uteroglobin, a steroid-dependent secretory protein first discovered in the rabbit uterus during early pregnancy, is a potent phospholipase A2 inhibitor. We found that uteroglobin also inhibited human and rabbit phagocyte chemotaxis in response to formyl peptide attractants in a dose-dependent manner. Half-maximal inhibition was at 1.2 microM. Uteroglobin did not compete with a formyl peptide for its receptor but inhibited internalization of radiolabeled formyl peptide. Uteroglobin appears to inhibit chemotaxis by a mechanism different from that of dansylcadaverine, a well studied inhibitor of endocytosis. Unlike dansylcadaverine, uteroglobin did not have any effect upon the synthesis of phosphatidylcholine or phosphatidylinositol. It is suggested that uteroglobin may protect trophoblastic cells from the defense system of the host not only by binding to antigenic determinants of embryonic cells but also by impairing migration of phagocytes, one of the primary components of the immune defense system. These results may explain why embryonic cells do not elicit an inflammatory response in the uterine endometrium during pregnancy.

Identification and partial characterization of a low-molecular-weight inhibitor of leukotaxis from fibrosarcoma cells.

Lysate from T-241 murine fibrosarcoma cells contains a low-molecular-weight (Mr less than 1000), heat-stable peptide factor which has antichemotactic activity for both macrophages and polymorphonuclear leukocytes in vitro. The tumor factor was partially purified from an alcohol extract of the fibrosarcomas by gel filtration, anion exchange chromatography, and paper chromatography successively. This factor inhibits both the hydrolytic cleavage of the peptide attractant N-formylmethionylleucylphenylalanine by polymorphonuclear leukocytes and the methylation of both protein carboxyl groups and membrane phospholipids. Furthermore, the factor does not appear to compete with N-formylmethionylleucylphenylalanine for its receptor. The tumor-derived material, therefore, affects biochemical reactions believed to have roles in the expression of an adequate leukotactic response. These data suggest that depressed inflammatory responses at sites of neoplasms may result in part from release of small, potent inhibitors of leukotaxis from tumors themselves.

Adherence and regulation of leukotaxis.

PMNs upon stimulation by a chemoattractant adhere to a substratum and then in amoeboid fashion migrate toward the source of the attractant. We have studied molecular events in both adherence and migration and have arrived at the following conclusions: 1) PMNs, like other motile cells such as highly metastatic tumor cells, can use laminin to attach to Type IV basement membrane collagen. PMNs may use this anchoring mechanism in their emigration from the vasculature. 2) Attached cells may be stimulated to migrate as a result of the chemo-attractant-induced inactivation of lipomodulin, a natural inhibitor of phospholipase A2, an enzyme that may be essential for chemotaxis. 3) The substrate for this enzyme is generated by both the CDP-choline and transmethylation pathways. These pathways may be regulated by another enzyme, transglutaminase (TGase). 4) Natural substrates of TGase, such as uteroglobin, inhibit leukocyte chemotaxis, again suggesting a regulatory role for TGase in chemotaxis. 5) Tumor cells also produce inhibitors of chemotaxis. In addition to protecting the tumor from the host's phagocytes, these inhibitors may be related to normal modulators of cell motility. Therefore, determination of their mode of action could increase our understanding of this type of cell behavior.

Studies of glycogen-induced inflammation of mice. Dynamics of inflammatory responses and influence of antiinflammatory drugs and protease inhibitors.

The intraperitoneal injection of glycogen in the mouse resulted, shortly thereafter, in the accumulation of 14-23 million neutrophils in the peritoneal cavity and a four-fold increase in the numbers of circulating neutrophils. Preceding the influx of leukocytes, the exudation of plasma proteins and the chemotactic activity for mouse neutrophil in vitro increased in the peritoneal fluid. Among various protease inhibitors examined, chymostatin alone suppressed the plasma protein exudation. Indomethacin and dexamethasone reduced the accumulation of white cells and protein exudation. These nonsteroidal and steroidal antiinflammatory drugs were equally effective whether given simultaneously with or 60 min before glycogen or whether administered intraperitoneally or orally. Colchicine showed a suppressive effect on the leukocyte accumulation but enhanced the protein exudation.