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Murine IgG3 anti-IgG2a rheumatoid factor (RF) monoclonal antibodies (mAb) with cryoglobulin activity are able to induce skin leukocytoclastic vasculitis and glomerulonephritis resembling "wire-loop" glomerular lesions in normal mice. Since polymorphonuclear leukocyte (PMN) infiltration is one of the major pathological changes observed in both types of lesions, we determined the role of PMN and complement in the generation of these two different lesions, induced by 6-19 IgG3 RF mAb, by interfering with adhesion molecules known for their involvement of PMN-endothelial cell interaction or by depleting mice of their PMN or C3. Our results have demonstrated that first, the PMN-endothelial cell interaction mediated by leukocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) was crucial for the generation of 6-19 RF mAb-induced skin leukocytoclastic vasculitis, but not for glomerular lesions; second, PMN played an active role in the development of "wire-loop" glomerular lesions; in the absence of the PMN glomerular infiltration, 6-19 RF mAb induced a different type of glomerular lesions, characterized by voluminous intracapillary thrombi and mesangial deposits, but not subendothelial deposits; and third, the activation of the complement system did not appear to play a major role in both skin and glomerular lesions.

Three major components of the plasminogen activators (PA)/plasmin system are synthesized physiologically in glomeruli, and can be involved in glomerular proteolysis and extracellular matrix metabolism: tissue-type PA (tPA), urokinase (uPA) and PA inhibitor type 1 (PAI-1). To explore the possible role of a dysregulation of the plasmin protease system in the development and progression of lupus-like glomerulonephritis, we studied the expression of the renal plasmin protease components during the course of the disease, either acute, induced by IgG3 monoclonal cryoglobulins, or chronic, occurring spontaneously in three different lupus-prone mice: (NZBxNZW)F1, BXSB and MRL-lpr/lpr. RNase protection assays and in situ hybridizations revealed a marked glomerular induction of PAI-1 mRNA abundance without any significant changes in renal tPA and uPA mRNA levels in the two different types of lupus-like glomerulonephritis. The overexpression of PAI-1 mRNA occurred in parallel with a significant decrease in glomerular tPA-catalyzed enzymatic activity as determined by zymographic analysis. In addition, a concomitant increase in glomerular expression of transforming growth factor beta 1 (TGF-beta 1) mRNA was observed. The demonstration of a close correlation between the PAI-1 and TGF-beta 1 mRNA levels and the severity of lupus-like glomerular lesions suggests that a pertubation of the glomerular PA/PAI balance, resulting from a marked TGF-beta 1-mediated induction of PAI-1 gene expression, plays an important role in the progression of lupus-like glomerular lesions, leading to glomerulosclerosis.

The treatment of hemophilia and conditions that frequently afflict hemophilic patients, such as arthropathy, HIV infection, and viral hepatitis, are discussed. Long-term prophylaxis with Factor VIII or IX is very successful at preventing disabling arthropathy. Much research is being done on gene therapy and prolonged periods of Factor VIII and IX expression have already been achieved in animals. In HIV-seropositive hemophilic patients the CD4 count appears to decline more slowly in patients treated with higher purity than with lower-purity products. Thermoresistant non-lipid-enveloped viruses, such as parvovirus, do not become inactivated by the currently used virucidal methods.

Recent investigations have shown that in the murine kidney urokinase (uPA) and tissue-type plasminogen activator (tPA) are synthesized and released in urine by tubular epithelial cells, raising the possibility that plasminogen activators (PAs) may be involved in the maintenance of patency and fluidity in renal tubules. To further investigate the contribution of the PA system in renal pathology, we have determined the effects of LPS on the renal production of PAs: we localized PA-catalyzed proteolysis by zymographic analysis of tissue sections and studied the accumulation of mRNAs for PAs and their inhibitors (PAI-1 and PAI-2) by in situ hybridization. Both a single and two injections of LPS induced a dramatic reduction in urinary and renal uPA enzymatic activity; this decrease in catalytic activity was attributable to a reduction in uPA mRNA levels in both proximal and distal tubules. By contrast, we noticed a marked increase of tPA mRNA content in glomerular cells which was not accompanied by a concomitant increase in tPA-mediated proteolytic activity. In addition, a major up-regulation in PAI-1 mRNA levels was observed throughout the kidney, while PAI-2 mRNA was not detectable in the kidneys of control or LPS-injected animals. Our investigations document the profound alterations of the PA/PAI balance in renal tissue following in vivo LPS administration. They suggest that imbalanced extracellular proteolysis might participate in the alterations of kidney function observed in septic shock.

The 4-5-6 configuration on the MMPI for females has been associated with problems in the direct expression of anger, as well as excessive dependency and affectional needs (Greene, 1980). Because these characteristics frequently have been ascribed to bulimic women, we hypothesized that the incidence of the 4-5-6 configuration would be greater for bulimic women (n = 26) than for female outpatients (n = 40) or a nonpsychiatric population (n = 31). We did not find the predicted differences in incidence of the 4-5-6 configuration in a study that used conventional cut-offs and treated the configuration as a discrete variable. However, when the characteristic was measured as a continuous variable, the nonpsychiatric population differed significantly from both clinical populations. Results are discussed in terms of feminine role conflict as a factor that differentiates women who seek psychiatric treatment from those who do not.

Two hemodialysis membranes, polyacrilonitrile (AN 69) and cellulose acetate (CA), were compared for their effects on complement and hemostasis. Two groups of 5 patients, in dialysis for more than 5 years, were successively dialysed for 4 weeks periods with each type of membrane. We measured C3a (complement activation), platelets and beta-thromboglobulin (platelet activation), thrombin-antithrombin III complexes and fibrinopeptide A (coagulation activation), using C-Reactive Protein as a control for dilution effects. As previously shown, activation of complement was more important with CA than with AN 69 (p less than 0.01). In contrast, activation of coagulation (increase in fibrinopeptide A and thrombin-antithrombin III complexes) was more pronounced with AN 69 than with CA. This study emphasizes the need to consider different biological systems when the bioincompatibility of a hemodialysis membrane is evaluated.

3H-Noradrenaline release in the rabbit hippocampus and its possible modulation via presynaptic dopamine receptors was studied. Hippocampal slices were preincubated with 3H-noradrenaline, continuously superfused in the presence of cocaine (30 mumol/l) and subjected to electrical field stimulation. The electrically evoked tritium overflow from the slices was reduced by 0.1 and 1 mumol/l dopamine and apomorphine, but significantly enhanced by 10 mumol/l apomorphine or by 0.1 and 1 mumol/l bromocriptine. If the alpha 2-adrenoceptor antagonist yohimbine (0.1 mumol/l) was present throughout superfusion, the inhibitory effects of dopamine and apomorphine were more pronounced and even 10 mumol/l apomorphine and 1 mumol/l bromocriptine inhibited noradrenaline release. Qualitatively similar observations were made in the presence of another alpha 2-antagonist, idazoxane (0.1 mumol/l). In the presence of the D2-receptor antagonist domperidone (0.1 mumol/l) the inhibitory effects of dopamine were almost abolished, whereas both apomorphine (greater than 1 mumol/l) and bromocriptine (greater than 0.01 mumol/l) greatly facilitated noradrenaline release. The D2-receptor agonist LY 171555 (0.1 and 1 mumol/l) significantly reduced the evoked noradrenaline release whereas the D1-selective agonist SK & F 38393 was ineffective at similar concentrations. The effects of LY 171555 were abolished in the presence of domperidone (0.1 mumol/l) but remained unchanged in the presence of yohimbine or idazoxane (0.1 mumol/l, each). At 1 mumol/l the D2-receptor antagonists domperidone and (-)sulpiride significantly increased the evoked noradrenaline release by about 10%. However, at this concentration, domperidone (but not (-)sulpiride) affected also basal tritium outflow. Bulbocapnine and the preferential D1-receptor antagonists SCH 23390 enhanced the evoked noradrenaline release already at 0.1 mumol/l.(ABSTRACT TRUNCATED AT 250 WORDS)