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Biomedical subjects

R Lottenberg

Publications and source records attributed to R Lottenberg.

53 records · Page 3Linked to original sources
PubMed1987

Clinical efficacy of desmopressin acetate for hemostatic control in patients with primary platelet disorders undergoing surgery.

Desmopressin acetate (DDAVP) is efficacious in patients with von Willebrand's disease. It additionally appears to have value in patients with uremic or aspirin-induced platelet dysfunction. We report here three patients with primary platelet defects who had previously experienced grossly inadequate hemostasis to whom we administered DDAVP. Each successfully underwent surgical procedures with DDAVP as the only hemostatic agent. Although the mechanism of these salutary effects is unclear, DDAVP may exert an influence directly on the endothelium independent of correcting abnormalities of the factor VIII:von Willebrand complex associated with von Willebrand's disease.

Adolescent↗
PubMed1987

Identification of a specific receptor for plasmin on a group A streptococcus.

Certain group A streptococci demonstrate surface receptors that bind selectively to the key fibrinolytic enzyme, plasmin. These bacteria show no reactivity with the zymogen protein plasminogen or with other serine class proteases, such as trypsin or urokinase. Bacterium-bound plasmin retains its ability to cleave synthetic substrates and its ability to hydrolyze a fibrin clot. The bacterium-bound plasmin is not effectively regulated by its physiological regulator, alpha 2-plasmin inhibitor. This study is the first report of a bacterium-associated receptor for plasmin.

Fibrinolysin↗
PubMed1987

Physiology of hemostasis and its relationship to cardiovascular disease.

Our original understanding of coagulation was too simple. The waterfall or cascade system made sense but never gave clues either to points for control of the reaction or to areas to inhibit or reverse clotting. We now know critical points for control and reversal of hemostasis. By understanding more modern physiology, one is better able to design rational treatment programs to negate unwanted thrombosis. This chapter gives the reader a physiologic foundation to underscore the subsequent chapters.

Blood Coagulation↗
PubMed1986

The rapid inhibition of urokinase by plasma from pregnant women at risk for abruptio placenta.

Rapid inhibition of urokinase in plasma obtained from women in the third trimester of pregnancy was assessed by the addition of 75 IU urokinase per ml plasma, and measurement of residual urokinase activity with PyroGlu-Gly-Arg-pNA after 5 minutes incubation at 37 degrees C. The urokinase inhibitory capacity was markedly increased for the pregnant women compared to non-pregnant controls. Alpha 1-antitrypsin, alpha 2-macroglobulin and alpha 2-antiplasmin did not account for the activity. Inhibition was higher for women with multiple gestations or macrosomia (n = 11) compared to normal pregnant women (n = 35) suggesting that the placenta contributes significantly to the measured activity. Inhibition was lower for women with hypertension (n = 33) compared to the normal pregnant women. Although the etiology for this difference is unclear, the decreased inhibitory activity may contribute to the increased risk for placental abruption that is observed for this group of women.

Abruptio Placentae↗
PubMed1986

The action of factor Xa on peptide p-nitroanilide substrates: substrate selectivity and examination of hydrolysis with different reaction conditions.

Kinetic parameters for the action of bovine Factor Xa (EC 3.4.21.22) on 25 commercially available peptide p-nitroanilides have been determined. The selectivity constant, kc/Km, ranges from 1.5 X 10(1) to 2 X 10(6) M-1 X s-1 for the poorest and the best substates, respectively. The best substrates for Factor Xa were identified as those with arginine in the P1 position, and glycine in the P2 position. Quantitative distinction between lysine and arginine in the P1 position and other amino acids in the P2-P4 positions of the substrate is reported from the changes in the kinetic parameters for substrates differing in only a single amino acid in these positions. Effect of NaCl and CaCl2 concentrations and temperature on the action of Factor Xa on selected substrates have been assessed. Km values for Factor Xa hydrolysis of most substrates are greater than 100 microM. Solubility of the substrates consequently restricts measurements of reaction velocities to concentrations lower than desirable for optimally determining kc. Comparison of these kinetic parameters for Factor Xa with those of thrombin (Lottenberg, R., Hall, J.A., Blinder, M., Binder, E. and Jackson, C.M. (1983) Biochim. Biophys. Acta 742,539-557) for these same substrates indicates that the greater hydrolytic efficiency of thrombin is due primarily to lower Km values.

Anilides↗
PubMed1985

Recurring thromboembolic disease and pulmonary hypertension associated with severe hypoplasminogenemia.

In a patient with pulmonary hypertension and a history of recurrent venous thrombosis, plasma concentrations of all known coagulant and inhibitor proteins were normal except for severe deficiency of plasminogen. Repeated analyses showed the circulating plasma plasminogen level to be 30% of normal by either functional or immunologic methods. We sought evidence for either increased activation of plasminogen or for dysplasminogen. There was no evidence for the former. Purified plasminogen studies disclosed a normal number of active sites and normal activation. Generated plasmin had normal catalytic activity. Isoelectric focusing disclosed normal distribution of isoforms. Affinity chromatography with lysine-sepharose showed the presence of the two variant forms; however, an increased proportion of the protein eluted in the first peak. Danazol administration induced an increase in circulating plasminogen, but the differences in affinity chromatography elution profile remained. We conclude that this patient has a deficiency of normally functioning plasminogen, probably due to decreased synthesis.

Adult↗
PubMed1983

The action of thrombin on peptide p-nitroanilide substrates. Substrate selectivity and examination of hydrolysis under different reaction conditions.

Kinetic parameters for the action of bovine alpha-thrombin on 24 commercially available peptide p-nitroanilides have been determined. The selectivity constant, kcat/Km, ranges from 3.3 X 10(1) to 1.1 X 10(8) M-1 X S-1 for the poorest and the best substrates, respectively. The best substrates for thrombin were identified as those with arginine in the P1 position, proline or a proline homolog in the P2 position, and an apolar amino acid in the P3 position. Quantitative distinction between lysine and arginine in the P1 position and other amino acids in the P2-P4 positions of the substrate is reported from the changes in the kinetic parameters for substrates differing in only a single amino acid in these positions. Effects of NaCl, CaCl2 and poly(ethylene glycol) concentrations, pH and temperature on the action of thrombin on selected substrates have been assessed. A source of large systematic error in thrombin concentration estimates was identified as resulting from adsorption losses. These losses were eliminated by inclusion of poly(ethylene glycol) in dilution and reaction buffers.

Aniline Compounds↗
PubMed1983

Solution composition dependent variation in extinction coefficients for p-nitroaniline.

The dependence of the extinction coefficients for para-nitroaniline on solution composition has been investigated. The p-nitroaniline absorption spectrum is red-shifted with increasing ionic strength, with the consequence that the extinction coefficients at fixed wavelengths may vary significantly. The isosbestic wavelength for peptide p-nitroanilide/p-nitroaniline mixtures is similarly shifted. Poly(ethylene glycol) and bovine albumin, two additives frequently employed to eliminate enzyme loss from adsorption to cuvette and dilution vessel surfaces, also induce shifts in the p-nitroaniline spectrum. The use of a difference extinction coefficient at 381 nm, the p-nitroaniline maximum wavelength, is proposed to minimize the error resulting from solution composition dependent spectral shifts.

Aniline Compounds↗
PubMed1983

The syndrome of idiopathic myelofibrosis. A clinicopathologic review with emphasis on the prognostic variables predicting survival.

We describe here a series of 88 consecutive patients with bone marrow fibrosis. Primary causes for the fibrosis were discovered in 26% of the cases shortly after the initial diagnosis. Pathology review of the remaining cases revealed an 8% incidence of "hairy cell leukemia" that had escaped detection originally. The remaining cases, characterized as having "unexplained bone marrow fibrosis" or "idiopathic myelofibrosis," are the subject of this study. The clinical and laboratory findings are compared to those reported in previous series of selected cases with similar features in which patients were diagnosed as having "agnogenic myeloid metaplasia," "myelosclerosis," or "myelofibrosis." A brief summary of the treatment modalities used, and the clinical course and outcome of these patients are also presented. There was a marked variability in the clinical severity of the disease and in the survival of these patients. A detailed statistical analysis of 40 variables at the time of initial diagnosis showed that the factors that best predicted a poor survival were unexplained fever, weight loss, night sweats, anemia and thrombocytopenia. On the other hand, the size of the spleen or of the liver, the degree of immaturity of the peripheral blood white cells, and the degree of fibrosis or cellularity in the bone marrow biopsy were of no detectable prognostic significance. These findings suggest that in patients with unexplained fibrosis of the bone marrow (the syndrome of idiopathic myelofibrosis) a poor prognosis is not a direct consequence of the marrow fibrosis or the associated extramedullary hematopoiesis, but rather is related to the presence and/or the severity of some unexplained primary marrow defect, which is also often associated with the nonspecific symptoms of a systemic illness.

Adolescent↗
PubMed1982

The action of thrombin on peptide p-nitroanilide substrates: hydrolysis of Tos-Gly-Pro-Arg-pNA and D-Phe-Pip-Arg-pNA by human alpha and gamma and bovine alpha and beta-thrombins.

Human and bovine alpha-thrombins (greater than 90% alpha form) with high fibrinogen clotting activities (approximately 3,000 U.S. units/mg protein) exhibit similar Michaelis menten kinetics with the p-nitroanilide tripeptide substrates Tos-Gly-Pro-arg-pNA (Chromozym-TH) and D-Phe-Pip-Arg-pNA (S-2238). The kinetic parameters at I = 0.11 M, 25 degrees C, pH 7.8 are: (Km = 4.18 +/- 0.22 and 3.61 +/- 0.15 microM; kcat = 127 +/- 8 and 100 +/- 1 s-1) for Chromozym TH and (Km = 1.33 +/- 0.07 and 1.50 +/- 0.10 microM; kcat = 91.4 +/- 1.8 and 98.0 +/- 0.5 s-1) for S-2238 for the human and bovine enzymes, respectively. Unlike the native enzyme forms, their "non-clotting" terminal degradative forms, human gamma-thrombin (approximately 5 units/mg) and bovine beta-thrombin (approximately 200 units/mg), give increased values for these parameters (km = 14.3 +/- 2.4 and 14.4 +/- 2.2 microM; kcat = 160 +/- 9 and 124 +/- 6 s-1) for Chromozym-TH; and (Km = 2.50 +/- 0.36 and 2.99 +/- 0.33 microM; kcat = 106 +/- 3 and 106 +/- 3 s-1) for S-2238. Based on these parameters, 50% degradation of human or bovine alpha-thrombins can be calculated to produce relatively small errors in the kinetic measurement of total thrombin concentrations (maximally 9% and 7% for Chromozym-TH; 7% and 3% for S-2238, respectively) if the kinetic parameters for all alpha forms are erroneously used and assays are at 150 microM substrate. This is in contrast to the large errors inherent in clotting activity measurements on thrombin mixtures. Incorporation of 1 mg/ml of polyethylene glycol 6,000 into assay solutions eliminates systematic errors otherwise caused by thrombin adsorption to surfaces and enables thrombin to be accurately assayed at concentrations less than 0.1 nM or 0.01 clotting unit/ml of alpha-thrombin.

Adsorption↗
PubMed1981

Iron studies in hemophilia.

Although iron deficiency is not recognized as a usual complication of hemophilia, we questioned whether intermittent occult loss of blood in urine or stool might predispose hemophiliacs to chronic iron deficiency. Seven men with factor VII and one with factor IX deficiency were studied. Blood studied, bone marrow aspirates, urine and stool samples, and ferrokinetics with total-body counting up to five months were examined. These data showed no excessive loss of blood during the study period; however, marrow iron stores were decidedly decreased, being absent in four subjects. We suggest that in some hemophiliacs, iron deposits in tissues such as synovial membranes may form a high proportion of the body's total iron stores.

Bone Marrow↗
PubMed1979

Pulmonary histoplasmosis associated with exploration of a bat cave.

Approximately 14 days after exploring a limestone cave in northcentral Florida in February 1973, an 18-year-old female developed a respiratory illness with pronounced shortness of breath and cyanosis. The following day, an 18-year-old male presented to the hospital with similar complaints. The association of illness with their recent caving experience prompted further epidemiologic investigation. Twenty-nine members of a church-sponsored youth group explored the implicated cave. Twenty-three of them later became ill with complaints of cough, afternoon fever and sweats, chest discomfort, and dyspnea on exertion. Histoplasmin skin tests were positive in 18 of 24 individuals tested. Serum for complement fixation (CF) was positive in 12 of 26. Testing of area residents revealed a low incidence of skin test and CF positivity (7% and 0%, respectively). That spelunkers are at risk of acquiring pulmonary histoplasmosis has been noted previously; in Florida this has been related to the exploration of caves infested with bats. This is the largest reported outbreak of acute pulmonary histoplasmosis that has been associated with spelunking and further points out that only those individuals who enter the cave are at risk of acquiring the disease, and not those who reside in the surrounding area.

Adolescent↗
PubMed1977

Immune-complex glomerulonephritis in a patient with mixed connective tissue disease.

Renal involvement and hypocomplementemia in mixed connective tissue disease are reported to be rare. A patient is described here with mixed connective tissue disease and persistently low serum C'3 levels in whom renal insufficiency and nephrotic syndrome developed secondary to immune-complex glomerulonephritis. Light microscopy of the renal biopsy specimen showed predominantly a membranous lesion. Immunofluorescent staining showed granular deposition along the basement membrane of immunoglobulin G, immunoglobulin M, fibrinogen and C3. Electron microscopy showed numerous electron-dense deposits along the glomerular capillary membrane and in the mesangium.

Adult↗
PubMed1976

Chronic painless hematuria and urethral bleeding as the presenting manifestations of Osler-Weber-Rendu disease.

A case of a young man with profound iron deficiency anemia, chronic painless hematuria and urethral bleeding is presented. He had the typical cutaneous findings of Osler-Weber-Rendu disease (hereditary hemorrhagic telangiectasia). Appropriate urological studies demonstrated bladder and urethral telangiectases, with no other explanation for the bleeding. Osler-Weber-Rendu disease should be considered in the differential diagnosis of chronic painless hematuria.

Adult↗