Treatment of refractory rheumatoid arthritis with a monoclonal antibody to intercellular adhesion molecule 1.

Objective: To assess the safety and efficacy of a monoclonal antibody (MAb) to intercellular adhesion molecule 1 (ICAM-1; CD54) in rheumatoid arthritis (RA).

Methods: A phase I/II, open-label, dose-escalation study of 32 patients.

Results: During treatment, a peripheral CD3+/CD4+ lymphocytosis was noted, and several patients demonstrated transient cutaneous anergy, which suggests that therapy modified T cell recirculation.

A phase I trial of immunosuppression with anti-ICAM-1 (CD54) mAb in renal allograft recipients.

Several adhesion molecules contribute to the interaction between T cells and antigen presenting cells or target cells. Leukocyte function-associated molecule-1 (LFA-1[CD11a/CD18]) and intercellular adhesion molecule-1 (ICAM-1 [CD54]) are one such critical adhesive receptor-counter-receptor combination. The importance of ICAM-1 dependent adhesion in the rejection response was initially demonstrated in cynomolgus renal allograft recipients treated with the anti-ICAM-1 murine monoclonal antibody BIRR1.

Effects of fish oil on glomerular function in rats with diabetes mellitus.

The mechanisms responsible for hyperfiltration in diabetes mellitus (DM) as well as for the initiation and progression of diabetic nephropathy are not fully elucidated. Enhanced prostaglandin E2 (PGE2) production has been invoked in the former and thromboxane (TXB2) and hyperlipidemia in the latter. Fish oil (FO)-enriched diets can favorably alter eicosanoid synthesis and serum lipid profiles.

A fish oil diet preserves renal function in nephrotoxic serum nephritis.

Fish oil diets preserve renal function in murine lupus, but we have found that these diets accelerate renal deterioration in renoprival nephropathy. In this study we examined the effects of dietary fish oil in accelerated nephrotoxic serum nephritis. For 1 month, 14 female rats were fed diets that differed only in fat composition, containing either menhaden (fish) oil or beef tallow (control).

Interactions of low density lipoprotein with rat mesangial cells.

Hyperlipidemia may contribute to the pathogenesis of glomerular sclerosis. We therefore studied binding and uptake of low density lipoprotein (LDL) by cultured rat mesangial cells. In addition effects of LDL on PGE2 synthesis and cell proliferation were determined.

Eicosapentaenoic and dihomo gamma linolenic acid metabolism by cultured rat mesangial cells.

To better understand the effects of dietary fatty acid manipulations on glomerular function, we compared mesangial incorporation, release, and metabolism of arachidonic (AA), eicosapentaenoic (EPA), and dihomo gamma linolenic (DHG) acids. We found marked differences in mesangial handling of these fatty acids. AA was incorporated into lipids of mesangial cells much more rapidly than EPA or DHG.

Comparison of glomerular and mesangial prostaglandin synthesis and glomerular contraction in two rat models of diabetes mellitus.

Enhanced prostaglandin production is postulated to contribute to altered vascular reactivity and glomerular hyperfiltration in early insulin-deficient diabetes mellitus. Rats with streptozocin-induced diabetes (STZ-D) show glomerular hyperfiltration and develop renal disease. BB rats with genetic diabetes (BB-D) also hyperfilter but have only minor renal lesions.

Effects of dietary fish oil on renal insufficiency in rats with subtotal nephrectomy.

We studied the effects of fish oil on the progression of renal insufficiency in rats with subtotal nephrectomy. Five weeks after a 1-2/3 nephrectomy, sixteen rats were fed two different diets which differed only in fat composition. Lipid in the control diet was primarily beef tallow; that of the experimental diet, menhaden oil.

Contraction and relaxation of cultured mesangial cells on a silicone rubber surface.

Glomerular mesangial cells (MC) in culture are believed to contract or relax in response to agents such as angiotensin II and cyclic AMP. However, cells grown on glass or plastic surfaces are limited in their response to vasoactive agents because of the rigid surfaces to which they adhere; thus, interpretation of a change in shape as contraction, relaxation, or detachment is difficult. We have grown MC on a flexible silicone rubber (dimethylpolysiloxane) substrate (DMPS), and studied with sequential photographs several models of cell contraction, relaxation, and detachment.

Dopamine attenuates the contractile response to angiotensin II in isolated rat glomeruli and cultured mesangial cells.

Recent evidence suggests that dopamine may alter kidney function by actions not only in the renal vasculature but also at the glomerular-mesangial level. We studied this phenomenon by examining the ability of dopamine to antagonize the contractile properties of angiotensin II in isolated rat glomeruli and cultured mesangial cells. In isolated rat glomeruli angiotensin II caused a decrease in the planar surface area, indicating glomerular contraction, an effect that was abolished by coincubation with dopamine.

Glomerular prostaglandins, angiotensin II, and nonsteroidal anti-inflammatory drugs.

The glomerulus can, in part, regulate its own flow and filtration characteristics, both of which are determinants of the glomerular filtration rate. This occurs in part as the result of interactions between vasoconstrictors, e.g.

Sublimed (inorganic) sulfur ingestion. A cause of life-threatening metabolic acidosis with a high anion gap.

We describe a 66-year-old woman undergoing hemodialysis treatment who developed life-threatening metabolic acidosis (pH of 6.67) with a high anion gap (41 mEq/L [41 mmol/L]) and marked hyperkalemia (9.1 mEq/L [9.

Effects of leukotrienes on isolated rat glomeruli and cultured mesangial cells.

Several vasoactive substances influence glomerular function in vivo and alter glomerular surface area and prostaglandin (PG) synthesis in vitro. Leukotrienes (LT) LTC4 and LTD4 may also influence glomerular function in vivo and in the isolated perfused kidney. We therefore compared the effects of LT with those of angiotensin II (ANG II), arginine vasopressin (AVP), and platelet activating factor (PAF) on planar surface area of isolated rat glomeruli and the shape change of cultured mesangial cells and their PG synthesis.

Angiotensin II and eicosanoids in the control of glomerular size in the rat and human.

We examined the possibility that glomerular prostaglandin E2 (PGE2) regulates the action of angiotensin II (ANG II) on mesangial contraction and filtration surface area. Using isolated rat glomeruli we indirectly assessed mesangial contraction and filtration surface area through measurements of glomerular planar surface area (GPSA) by image-analysis microscopy. ANG II reduced GPSA by approximately 20% in human and rat glomeruli, with threshold concentrations of 1 X 10(-13) M and maximum effect at 5 X 10(-11) M ANG II.

Priapism and dialysis.

Ninety-three dialysis units located in the tri-state area were surveyed for the prevalence of priapism. Seventeen of 3,337 male patients experienced an episode of priapism. All of these episodes occurred either during or 2-7 h after dialysis, suggesting a cause-and-effect relationship.

Membranous nephropathy associated with primary biliary cirrhosis and bullous pemphigoid.

Membranous nephropathy has been shown to be an immune-mediated lesion in both human and experimental animal models. Primary biliary cirrhosis and bullous pemphigoid are also diseases of probable autoimmune origin. In this brief report, a woman with all three disease entities is described and an interrelationship among the three is discussed.

Effects of a stable prostaglandin analogue, L-644,122, in healthy and hypertensive men.

L-644,122 is a chemically stable vasodilator prostaglandin analogue. It is a selective renal vasodilator in dogs. The object of the present study was to determine whether it increases effective renal plasma flow (ERPF) in man.

Mechanisms of the nephrotoxicity of non-steroidal anti-inflammatory drugs.

Renal cortical prostaglandin synthesis, particularly by arterioles and glomeruli, is important to preserve renal blood flow (RBF) and glomerular filtration rate (GFR). Glomeruli and arterioles synthesize not only the vasodilatory prostaglandins PGE2 and PGI2, but also the vasoconstrictor, thromboxane A2. The primary renal cortical actions of these prostaglandins are renal vasodilatation and maintenance of GFR (PGE2 and PGI2) or renal vasoconstriction and reduction of GFR (thromboxane A2).

Renal cyclo-oxygenase and lipoxygenase products in health and disease.

Renal glomeruli have cyclo-oxygenase and lipoxygenase enzymes which convert arachidonic acid to prostaglandins, thromboxane and 12-hydroxyeicosatetraenoic acid. Glomerular epithelial and mesangial cells, in culture, also synthesize these arachidonate products. Angiotensin and vasopressin contract mesangial cells and stimulate mesangial synthesis of PGE2.

Arachidonate metabolites and the control of glomerular function.

The glomerulus is a dynamic structure capable of regulating the glomerular filtration rate (GFR) by mesangial contraction, thereby decreasing Kf. The mesangium contracts in response to angiotensin II (AII) and arginine vasopressin (AVP), both of which are potent stimuli of vasodilatory prostaglandin (PG) production. We studied interactions among these opposing factors in glomeruli.

Prostaglandin synthesis by rat glomerular mesangial cells in culture. Effects of angiotensin II and arginine vasopressin.

Arginine vasopressin (AVP) and angiotensin II (ANG II) reduce the glomerular filtration rate and ultrafiltration coefficient. Vasodilatory prostaglandins (PG) antagonize these effects. AVP and ANG II also cause mesangial cell contraction.