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Biomedical subjects

I M Goldstein

Publications and source records attributed to I M Goldstein.

At least 73 records · Page 4Linked to original sources
PubMed1981

Effect of high-dose methylprednisolone infusion on polymorphonuclear leukocyte function in patients with systemic lupus erythematosus.

We have studied the effect of high-dose (1 gm) methylprednisolone infusion on polymorphonuclear leukocyte (PMN) function in 11 patients with active systemic lupus erythematosus (SLE). The only alteration of polymorphonuclear leukocyte function produced consistently by methylprednisolone was decreased adherence to plastic surfaces when tested 2 hours after infusion. This steroid-induced abnormality, however, was transient. Cells obtained from patients 24 hours after a single dose of drug exhibited normal adhesiveness. These results indicate that single, large doses of methylprednisolone do not produce long-lasting abnormalities of PMN function in patients with lupus.

Adolescent↗
PubMed1981

Complement-derived chemotactic activity is generated in human serum containing uroporphyrin after irradiation with 405 nm light.

Patients with porphyrias have varying degrees of photosensitivity, associated with elevated levels of porphyrins in plasma, erythrocyte, urine and/or feces. To investigate the role of complement in the pathogenesis of cutaneous lesions, varying amounts of uroporphyrin were added to normal human serum (0.1-10 microgram/ml), and the mixtures were then exposed to 405 nm irradiation. Such treatments result in the diminution of total hemolytic complement activity and hemolytic titers of C1, C4, C2, C3, and C5; furthermore, cleavage products of C3 and C5 were detected. Chemotactic activity for human polymorphonuclear leukocytes was generated that was inhibitable by incubation with anti-C5, but not with anti-C3 antisera. No chemotactic activity was generated in Mg++-EGTA treated serum nor in C4-deficient guinea pig serum. These data indicate that irradiation with 405 nm light of normal human serum containing uroporphyrin results in activation of the complement system via the classical pathway, and the generation of complement (C5)-derived chemotactic activity for human polymorphonuclear leukocytes.

Adult↗
PubMed1981

Why do implants fail?

Nylon 66 and polypropylene are chemotactic in human serum while PMMA from intraocular lenses is not. Chemotactic activity is unaltered by Ridley, 5 per cent NaOH, or ethylene oxide sterilization. Chemotaxis is but one manifestation of an overall inflammatory process that may be involved in implant-induced corneal and retinal dysfunction.

Adult↗
PubMed1981

Sudden blindness in acute pancreatitis. Possible role of complement-induced retinal leukoembolization.

During an episode of acute alcoholic pancreatitis, severe visual loss and the funduscopic appearance of Purtscher's retinopathy-a syndrome thought to be caused by posterior retinal microembolization-developed in a patient. We propose that emboli in this case may have consisted of aggregated granulocytes since plasma samples from eight to 12 patients with subsequently studied acute pancreatitis caused granulocyte aggregation in vitro. The aggregant was demonstrated to be an activated fragment of the complement system, derived from C5. Since we could generate identical granulocyte aggregating activity by treating serum or purified C5 with trypsin, we suggest that proteases released from an inflamed pancreas might have produced a C5-derived aggregant in this case, as well as in three other previously reported cases of acute pancreatitis and Purtscher's retinopathy. We conclude that complement-induced leukoembolization may be a previously unsuspected cause of vital-tissue damage.

Acute Disease↗
PubMed1981

Enhancement of the chemotactic activity of human C5a des Arg by an anionic polypeptide ("cochemotaxin") in normal serum and plasma.

The potent chemoattractant, C5a is converted rapidly to C5a des Arg by a carboxypeptidase-like enzyme in normal human serum and plasma. Highly purified human C5a des Arg, at concentrations less than 120 ng/ml, is devoid of chemotactic activity for polymorphonuclear leukocytes. We have found that normal human serum and plasma contain a heat-stable (56 degrees C for 30 min), anionic polypeptide ("cochemotaxin") that permits low concentrations of C5a des Arg (20 to 160 ng/ml) to exhibit significant chemotactic activity. The "cochemotaxin" was isolated from serum and plasma by ammonium sulfate fractionation, molecular sieve chromatography, and anion-exchange chromatography. It was purified by high-performance liquid chromatography and was found to have an Mr of approximately 60,000 (determined by sodium dodecylsulfate polyacrylamide gel electrophoresis). The concentration of "cochemotaxin" in normal serum and plasma was estimated to be 4.0 microgram/ml. Purified "cochemotaxin" acted in a concentration-dependent fashion to permit low concentrations (20 to 160 ng/ml) of C5a des Arg to attract polymorphonuclear leukocytes. Chemotactic activity varied with the input of C5a des Arg and "cochemotaxin" and was maximal when the 2 polypeptides were combined at equal protein concentrations. The profile of chemotactic activity exhibited by C5a des Arg and its "cochemotaxin" very closely resembled that exhibited by dilutions of activated serum and by highly purified C5a. These data suggest that the bulk of chemotactic activity generated in whole serum after complement activation can be accounted for by C5a des Arg and its "cochemotaxin".

Anions↗
PubMed1980

An immunoglobulin (IgG) inhibitor of polymorphonuclear leukocyte motility in a patient with recurrent infection.

We isolated from the serum of a patient with recurrent skin infections an IgG immunoglobulin that irreversibly inhibits the random motility and chemotactic responsiveness of polymorphonuclear leukocytes. Although the patient's leukocytes behaved like normal cells with respect to adherence, phagocytosis, degranulation, and generation of the superoxide anion, they did not migrate normally toward standard chemotactic stimuli. Normal human polymorphonuclear leukocytes behaved similarly after incubation with the patient's serum. Inhibition of motility was not associated with cyutotoxicity. Inhibitory activity could be removed completely from the patient's serum by treatment with either agarose-bound anti-human IgG or Sepharose-bound staphylococcal protein A. Exposure of normal polymorphonuclear leukocytes to as little as 1.25 microgram per milliliter (0.00125 g per liter) of the patient's purified IgG caused significant inhibition of random motility and chemotactic responsiveness (P < 0.01). Thus, IgG immunoglobulins can inhibit leukocyte motility specifically and irreversibly, and thereby adversely affect host defenses against invading microorganisms.

Cell Movement↗
PubMed1980

Generation of a chemotactic lipid from a arachidonic acid by exposure to a superoxide-generating system.

Certain products of arachidonic acid have been demonstrated recently to possess chemotactic activity for human polymorphonuclear leukocytes (PMN). Enzymatic (lipoxygenase, cyclooxygenase) generation of these lipid chemotaxins proceeds through the formation of intermediate lipid peroxides. Since lipid peroxidation can be mediated by oxygen-derived free radicals, we have examined whether chemotactically active products of arachidonic acid could be produced by exposing this unsaturated fatty acid to a superoxide-generating system. A lipid with potent chemotactic activity for human PMN was produced by incubating arachidonic acid with xanthine oxidase and acetaldehyde. Generation of chemotactic activity was time-dependent and could be inhibited to the greatest extent by scavengers of singlet oxygen (i.e., histidine, uric acid, and 2,5-dimethylfuran). Inhibition was also observed with scavengers of superoxide anion radicals (i.e., superoxide dismutase), hydrogen peroxide (i.e., catalase), and hydroxyl radicals (i.e., mannitol). Silica gel thin-layer radiochromatography demonstrated a single peak with chemotactic activity (Rf = 0.33-0.38) distinct from unaltered arachidonic acid. The product of arachidonic acid was chemotactic at a concentration of 3.0 ng/ml and chemokinetic at concentrations of 0.75-1.5 ng/ml. Since PMN produce oxygen-derived free radicals and singlet oxygen upon stimulation of their plasma membrane, and since arachidonic acid is widely distributed in human tissues, free radical-mediated generations of chemotactic activity from arachidonic acid may play an important role in amplifying inflammatory responses.

Arachidonic Acids↗
PubMed1980

Evidence of complement catabolism in experimental acute pancreatitis.

Serum specimens from guinea pigs with experimentally induced acute pancreatitis were examined for evidence of protease-antiprotease imbalance and complement catabolism. Pancreatitis was induced in 22 male Hartley guinea pigs by the injection of sodium taurocholate into the pancreatic parenchyma. Only a laparotomy was performed in 6 control animals. In 10 experimental animals that survived for less than 24 hours, there was a significant, early reduction of serum trypsin inhibitory capacity (a measure of antiprotease activity). Levels of total hemolytic complement as well as titers of hemolytic C3 and C4 fell significantly in all experimental animals during the first 24 hours. Factor B activity, however, did not change. Only serum from experimental animals contained chemotactic activity for human polymorphonuclear leukocytes. These findngs indicate that circulating complement components are cleaved during the course of experimental acute pancreatitis. As a consequence, complement-derived peptides are generated that may mediate local and systemic tissue injury.

Acute Disease↗
PubMed1980

Generation of a biologically active lipid from arachidonic acid by exposure to a superoxide-generating system.

A biologically active lipid was produced by incubating arachidonic acid with a superoxide-generating system consisting of xanthine oxidase plus acetaldehyde. The lipid proved to be a potent chemoattractant for human polymorphonuclear leukocytes and also was capable of inhibiting platelet aggregation induced either by arachidonic acid or by the endoperoxide analog, 9,11-azoprostanoid III. Generation of the biologically active lipid required the presence of all of the reactants, was time-dependent and could be inhibited by scavengers of superoxide, hydroxyl radicals, and singlet oxygen. Silica gel thin-layer radiochromatography demonstrated a single peak with biological activity, distinct from unaltered arachidonic acid. The biologically active lipid was most likely generated by the peroxidation of arachidonic acid. Biologically active products of arachidonic acid formed nonenzymatically by the action of oxygen-derived free radicals may play important roles in the mediation and modulation of inflammatory responses.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗