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Biomedical subjects

M Silverberg

Publications and source records attributed to M Silverberg.

At least 37 records · Page 2Linked to original sources
PubMed1992

Effect of Neurotropin on the activation of the plasma kallikrein-kinin system.

Bradykinin (BK), an important mediator of allergic reactions and pain induction, is released by the activation of the plasma kallikrein-kinin (K-K) cascade. Neurotropin is a biological material obtained from inflamed rabbit skin inoculated with vaccinia virus and is widely used clinically in Japan as an effective agent for these disorders. Since its mechanism of action is not clearly known, we have investigated the effects of Neurotropin on the human plasma K-K system. In dextran sulfate-activated plasma, Neurotropin inhibited the formation of BK, the cleavage of high molecular weight kininogen (HK) and the formation of kallikrein-C1 inhibitor and activated coagulation factor XII (FXIIa)-C1 inhibitor complexes. Experiments using purified enzyme of the K-K cascade indicated that Neurotropin inhibited surface-mediated activation of coagulation factor XII (FXII) and the activation of prekallikrein by FXIIa. Neurotropin also inhibited the binding of FXII and HK to the activating surface. These data suggest that the ameliorating effects of Neurotropin in allergic disorders and pain syndromes may be related to this ability to inhibit activation of the K-K cascade and consequently the formation of BK.

Animals↗
PubMed1992

Factors affecting the rate of contact activation in human plasma.

The rate of high molecular weight kininogen cleavage in human plasma treated with dextran sulfate depends largely on the length of preincubation at 37 degrees C and the sample size during preincubation. The longer the preincubation with aliquots < 100 microliters, the more refractory to contact activation the plasma became. This effect is not due to prekallikrein or factor XII consumption/inhibition since both proteins are functional in clotting assays and detectable in immunoblots even after prolonged incubation times at 37 degrees C.

Blood Coagulation↗
PubMed1991

Continuous infusion gallium nitrate for patients with advanced refractory urothelial tract tumors.

A Phase I-II trial of gallium nitrate was conducted in 40 patients with bidimensionally measurable urothelial tract tumors who had failed to respond to combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin. Partial responses were observed in 4 of 23 patients (17.4%) who received 350 mg/m2/d or more for 5 days by continuous intravenous infusion. In two additional patients who received 350 mg/m2/d or more, a minor response and a mixed response were observed. The median duration of response was 4 months (range, 2 to 8 months). A dose-response relationship was suggested because no responses were observed in 17 patients who received less than 350 mg/m2/d. Myelosuppression was minimal. The dose-limiting toxic reaction was a reversible optic neuropathy that occurred in 3 of 11 patients who received 400 mg/m2/d. Further evaluation of infusional gallium nitrate is warranted in patients with urothelial tract malignant tumors.

Adult↗
PubMed1991

Clinical pharmacology of the neuromuscular blocking agents.

Neuromuscular blocking agents are among the most commonly used drugs during general anesthesia. They compete with acetylcholine and interfere with the transmission of nerve impulses resulting in skeletal muscle relaxation. Based on their mechanism of action, neuromuscular blocking agents are classified as either depolarizing or nondepolarizing. Succinylcholine is a short-acting depolarizing agent. Commonly used nondepolarizing agents are curare (long-acting), pancuronium (long-acting), atracurium (intermediate-acting), and vecuronium (intermediate-acting). Neuromuscular blocking agents are used clinically to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery. This article provides an overview of the physiology of the neuromuscular transmission and summarizes our current knowledge on the use of these agents during general anesthesia.

Atracurium↗
PubMed1991

Chronic abdominal pain in adolescents.

Although there are very few prospective studies of CAP, organic causes of the problem are misdiagnosed probably in less than 5% of adolescents. Response to treatment seems to be better in males who have had signs and symptoms for less than 6 months, and is rather poor for patients with complaints exceeding 2 years. An organized nomenclature is necessary for classifying dysfunctional disorders, and physicians must recognize that these patients represent a heterogeneous population. In general, adequate data for the number of the adolescent population affected by these diseases is not available, so that physicians are still required to depend to a large extent on speculation and anecdotal information in assessing and managing these patients.

Abdominal Pain↗
PubMed1990

Cutaneous photosensitivity and coproporphyrin abnormalities in the Alagille syndrome.

Porphyria cutanea tarda-like blistering, fragility, and scarring of light-exposed skin was observed in four children with the Alagille syndrome. Abnormally elevated levels of serum porphyrins, of which coproporphyrin isomers I and III together accounted for 50%-89% of the total, were found in these four children but also in three other children with the Alagille syndrome without such skin lesions. The ratio for isomer I to III for total serum coproporphyrin concentration was determined in six cases; the concentration of isomer I was greater than or equal to that of isomer III in each case. Urinary total porphyrin excretion was found to be elevated in six of the seven cases, with 72% +/- 8% occurring as coproporphyrins I and III. The ratio for urinary coproporphyrin I to III was greater than or equal to 1 in six of these patients, the reverse of the typical normal isomer distribution. Inasmuch as the presence or absence of photocutaneous lesions did not correlate with levels of porphyrins in serum or urine, other factors may be involved in the pathogenesis of the skin lesions.

Adolescent↗
PubMed1989

Pathways of kinin formation and role in allergic diseases.

We have developed new assays for the assessment of the plasma kinin forming system which have increased sensitivity and specificity. We utilize double-antibody ELISA assays for quantitation of complexes of activated Hageman factor-C1 inhibitor, kallikrein-C1 inhibitor, and kallikrein-alpha 2-macroglobulin which reflect activation of each enzyme. The fraction of cleaved high-molecular-weight kininogen is determined by immunoblotting using a monoclonal antibody to the light chain, and bradykinin is determined by radioimmunoassay. Activation of the Hageman factor-dependent pathway of kinin formation can occur when plasma is in contact with initiating surfaces or when C1 inhibitor function is diminished. The latter mechanism can occur in hereditary angioedema, in which the protein is absent or dysfunctional, or when plasma is diluted so that the effect of inhibitors is diminished and Hageman factor autoactivation is facilitated. Thus apparent "spontaneous" generation of bradykinin is seen upon incubation of plasma of hereditary angioedema patients under conditions in which normal plasma is unaffected. Studies of late-phase reactions have used a cutaneous model in which induced blisters are unroofed and challenged with antigen or buffer control using chambers which can be changed hourly. A time course of mediator release is obtained by assay of the blister fluids. Whereas most histamine is released during the first half hour, significantly elevated levels of activated Hageman factor and kallikrein complexes with C1 inactivator are seen in antigen-challenged sites between 4 and 6 hr. The presence of such complexes correlated with the presence of late-phase reactions rather than the histamine values or the magnitude of the immediate reaction. Although late-phase reactions are characterized by cellular infiltration, release of a variety of inflammatory low-molecular-weight mediators, and deposition of fibrin, activation of the Hageman factor-dependent pathway of kinin formation is also likely to be contributory.

Angioedema↗
PubMed1989

Studies on contact activation: effects of surface and inhibitors.

Contact activation is initiated when the plasma proteins, Hageman factor (factor XII), prekallikrein and high molecular weight kininogen interact with negatively charged materials. The activation of the intrinsic pathway of blood coagulation and the production of bradykinin are among the sequelae of contact activation. The kinetics of the activation of the contact system are modified by plasma inhibitors, C1 inhibitor being quantitatively the most important. We propose that the activation of the system requires that the stimulus provided by the surface must be greater than a threshold value to overcome the effects of the inhibitors. We show in this paper that the amount of surface required for activation is much reduced in the absence of C1 inhibitor (Hereditary Angioedema) or in the cold where the inhibitor loses much of its effectiveness. Antithrombin III inhibition of activated Hageman factor is augmented by heparin which is also an activator of Hageman factor. The rate constants for inhibition remain much lower than for C1 inhibitor, however.

Antithrombin III↗
PubMed1988

Prekallikrein.

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Blood Coagulation Tests↗
PubMed1987

The autoactivation of factor XII (Hageman factor) induced by low-Mr heparin and dextran sulphate. The effect of the Mr of the activating polyanion.

Human Factor XII is known to undergo autoactivation in the presence of dextran sulphate of Mr 500,000. We have now studied the dependence of this reaction on the Mr of the dextran sulphate by using fractions resolved by gel filtration. We have found that autoactivation can be induced by dextran sulphate fractions with Mr as low as 3000, and there is a marked dependence of the rate constant of autoactivation on the Mr value. Fractions with Mr below 8000 gave very low rates of autoactivation; there was a sharp increase in the rate obtained when the Mr of the dextran sulphate was greater than 10,000. Various preparations of heparin were also able to support the autoactivation of Factor XII and gave a very similar relationship between molecular size and reaction rate. The data provide support for the hypothesis that the mechanism by which the 'surface' acts in contact activation involves the presence, on the same particle, of multiple binding sites for the proteins.

Binding Sites↗