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Biomedical subjects

M J Weinstein

Publications and source records attributed to M J Weinstein.

At least 37 records · Page 2Linked to original sources
PubMed1984

Two distinct forms of Factor VIII coagulant protein in human plasma. Cleavage by thrombin, and differences in coagulant activity and association with von Willebrand factor.

We have characterized Factor VIII coagulant protein, present in normal human plasma, that reacts with a specific human 125I-labeled anti-human VIII:C antigen Fab antibody fragment. Two major Factor VIII coagulant antigen populations were present. The first, approximately 85% of the total antigen, was bound to von Willebrand factor and when tested in a standard one-stage assay had Factor VIII coagulant activity. The second antigenic population, eluting near fibrinogen when plasma was gel filtered, was not bound to von Willebrand protein, did not have Factor VIII coagulant activity unless activated, but did block anti-VIII:C Fab neutralization of clotting activity. The two antigenic populations were separable by cryoprecipitation and agarose gel electrophoresis. Although the two antigenic populations differed in their Factor VIII coagulant activity and in their binding to von Willebrand factor, the principal member of both populations is of mol wt 2.4 X 10(5). Both antigens, when proteolyzed by thrombin, were quickly converted to a 1 X 10(5)-mol wt form in association with the appearance of VIII:C activity. The 1 X 10(5)-mol wt antigen was further slowly degraded to an 8 X 10(4)-mol wt form while Factor VIII coagulant activity declined. These results demonstrate the presence of an inactive Factor VIII coagulant protein in plasma, not associated with von Willebrand factor, that can react with thrombin to yield Factor VIII coagulant activity.

Antigens↗
PubMed1984

Abnormal VIII: von Willebrand factor patterns in the plasma of patients with the hemolytic-uremic syndrome.

Plasma VIII:von Willebrand factor antigen (VIII:vWF) levels were elevated approximately two- to eightfold in seven patients (three adults and four children) during acute episodes of thrombocytopenia, renal failure, and hemolytic anemia (the hemolytic-uremic syndrome, HUS). In all seven patients, there was an alteration in plasma VIII:vWF patterns during these acute HUS episodes, so that the largest VIII:vWF forms were relatively decreased. Plasma VIII:vWF multimer patterns returned to normal, or nearly to normal, as platelet counts returned to preexisting levels, even in the patients whose recovery of renal function was incomplete and whose plasma VIII:vWF antigen level remained above normal. The sister of one of the HUS patients had a similar clinical prodrome (gastroenteritis) that was not followed by thrombocytopenia or renal failure and was not accompanied by an elevated level or abnormal forms of plasma VIII:vWF. These results suggest that an alteration in VIII:vWF metabolism, distribution, or interaction with platelets is associated with acute HUS episodes. In contrast to patients with chronic relapsing thrombotic thrombocytopenic purpura, none of the HUS patients (either during or after the acute HUS episodes) had a defect in the conversion of unusually large VIII:vWF multimers derived from endothelial cells to the VIII:vWF forms found in normal plasma.

Adult↗
PubMed1983

Direct radioimmune detection in human plasma of the association between factor VIII procoagulant protein and von Willebrand factor, and the interaction of von Willebrand factor-bound procoagulant VIII with platelets.

The predominant procoagulant factor VIII (VIII:C) form in normal human plasma containing various combinations of anticoagulants and serine/cysteine protease inhibitors is a protein with mol wt 2.6 +/- 0.2 X 10(5). This protein can be detected by 125I-anti-VIII:C Fab binding and gel electrophoresis in the presence and absence of sodium dodecylsulfate (SDS) and is distinct from the subunit of factor VIII/von Willebrand factor (VIII:vWF) multimers. No larger VIII:C form is present in plasma from patients with severe congenital deficiencies of each of the coagulation factors, other than VIII:C. The mol wt approximately 2.6 X 10(5) VIII:C form is, therefore, likely to be the in vivo procoagulant form of VIII:C, rather than a partially proteolyzed, partially activated derivative of a larger precursor. About 60% of this procoagulant mol wt approximately 2.6 X 10(5) VIII:C form in plasma is present in noncovalent complexes with larger VIII:vWF multimers, which attach reversibly to platelet surfaces in the presence of ristocetin. This VIII:vWF-bound protein of mol wt approximately 2.6 X 10(5) may be the plasma procoagulant form of VIII:C which, after proteolytic activation, accelerates the IXa-mediated cleavage and activation of X postulated to occur on platelet surfaces.

Antigens↗
PubMed1983

Apparent molecular weight of purified human factor VIII procoagulant protein compared with purified and plasma factor VIII procoagulant protein antigen.

We have compared apparent molecular weights of purified factor VIII procoagulant protein (VIII:C) and VIII:C antigen (VIII:CAg) by two different NaDodSO4 gel electrophoretic techniques. In a discontinuous NaDodSO4-7.5% polyacrylamide system, reduced and unreduced VIII:C, purified from commercial factor VIII concentrates by a monoclonal antibody immunoadsorption technique, showed a major doublet at mol wt 0.79 and 0.8 X 10(5) and less intense bands extending up to 1.9 X 10(5). In NaDodSO4-4% polyacrylamide/0.5% agarose gels (NaDodSO4-4% PAAGE), purified VIII:C had a major band of mol wt 1.0 X 10(5), with minor bands of mol wt 0.96, 1.1, 1.4, 1.6, 1.8, 2.2, and 2.4 X 10(5). In NaDodSO4-4% PAAGE of 125I-anti-VIII:C-Fab-VIII:CAg complexes, the major and minor forms of VIII:CAg in purified VIII:C had the same molecular weight as above when calculated by subtracting the molecular weight of 125I-Fab from 125I-Fab-VIII:CAg. In both plasma and factor VIII concentrate, a band of mol wt 2.4 X 10(5) predominated, and minor VIII:CAg forms of mol wt 2.6, 1.8, 1.2 and 1.0 X 10(5) were also visible. We conclude that the molecular weight of plasma VIII:CAg forms agree with those derived from protein stains of purified VIII:C in the NaDodSO4-4% PAAGE system, but that consistently lower molecular weight values are obtained for purified VIII:C in the discontinuous system. Both native and either disaggregated or proteolyzed VIII:C species are present in the purified VIII:C preparation.

Antigens↗
PubMed1980

Treatment of the bleeding tendency in uremia with cryoprecipitate.

We gave cryoprecipitate to six patients with uremia and bleeding times prolonged to more than 15 minutes. After the infusion, all patients had shortened bleeding times; the times of five became normal. In four patients control of major bleeding episodes was attained, and five underwent major surgical or invasive procedures, with good hemostasis. After infusion the time before the nadir of the bleeding time was reached was between one and 12 hours. The bleeding time returned to pretreatment levels by 24 hours after infusion in five patients, and by 36 hours in the other patient. Platelet-aggregation studies before infusion gave normal results in three patients and abnormal results in three. There wasno change after infusion. Before infusion, levels of Factor VIII coagulant activity and Factor VIII von Willebrand activity were normal, Factor VIII-related antigen was increased, and crossed immunoelectrophoresis of Factor VIII-related antigen was normal. Our findings suggest that cryoprecipitate can temporarily correct the bleeding tendency in patients with uremia.

Adult↗
PubMed1979

Needle biopsy of intrancranial lesions guided by computerized tomography.

Biopsies can be performed directly with computerized tomography (CT) head scanners with some difficulty. The small scanning orifice does not allow enough room for needle placement; therefore, biopsy is difficult. In contrast, the scanning orifice of the CT body scanner is large enough to permit biopsies without hindrance. Over 300 CT-guided abdominal biopsy procedures have been performed at the Cleveland Clinic Foundation. We are reporting the technique and the results of 14 CT-guided brain biopsies. There were no complications in the series and an accurate diagnosis was made for 13 of the 14 patients.

Adult↗
PubMed1978

Quantitative abnormality of an Aalpha chain molecular weight form in the fibrinogen of cirrhotic patients.

The molecular weight heterogeneity of fibrinogen from the whole plasma of 12 normal and seven cirrhotic individuals was examined by means of a novel two-dimensional sodium dodecyl suphate (SDS) gel electrophoretic technique. Fibrinogen was first separated from other plasma proteins on a large pore gel, cut out of the gel, reduced, and separated into its component Aalpha, Bbeta and gamma chains on a second gel. Fibrinogen was resolved into two major bands, I and II, on the first gel. The ratio of fibrinogen II to fibrinogens I plus II was approximately 0.3 (range 0.2-0.35) for both normals and cirrhotic patients. Two major molecular weight (mol wt) forms of Aalpha chain were present in normal fibrinogen I: Aalpha/I and/or Aalpha/2, mol wt 7 X 10(4) and 6.7 X 10(4) respectively. Normal fibrinogen II contained either one of these Aalpha chains plus one of the smaller Aalpha chains, Aalpha/6--10, accounting for the 3--4 X 10(4) mol wt difference between bands I and II. Aalpha/2 comprised 33% of the total Aalpha chains (range 27--41%) in normal fibrinogen I and approximately 25% of the Aalpha chains in normal fibrinogen II. In contrast, fibrinogen I from six out of the seven patients contained a lower percentage of Aalpha/2 (range 10--25%). Similarly fibrinogen II from these patients was deficient in Aalpha/2, although the protein contained normal levels of lower mol wt Aalpha derivatives. No correlation was found between per cent fibrinogen II and per cent Aalpha/2 in either normal or cirrhotic subjects. These results suggest that at least two independent processes are responsible for the observed levels of Aalpha heterogeneity in normals and cirrhotics and that the process controlling Aalpha/2 production is a abnormal in cirrhotic individuals. This decrease in Aalpha/2 does not affect the coagulability of fibrinogen. Fibrin monomer aggregation studies indicate that a serum component is, in part, responsible for the abnormally transparent clot formed from the plasma of cirrhotics.

Blood Coagulation Tests↗
PubMed1978

Uptake of (methyl-14C)-sisomicin and (methyl-14C)-gentamicin into bacterial cells.

Eight sensitive strains (two Staphylococcus aureus, two Escherichia coli, two Pseudomonas aeruginosa and two Klebsiella pneumoniae) and four resistant Pseudomonas aeruginosa strains were used to study uptake of sisomicin and gentamicin by the bacterial cells. In eleven out of the twelve organisms studied employing (methyl-14C)-sisomicin and (methyl-14C)-gentamicin, uptake of the former was found higher that that of the latter. In one organism, the uptake of the two antibiotics was similar. This higher uptake of sisomicin may help explain the superior potency of the antibiotic in relation to gentamicin.

Bacteria↗
PubMed1977

Biotransformation of sisomicin to gentamicin C2b.

Sisomicin was transformed to gentamicin C(2b) by Micromonospora rhodorangea NRRL 5326. The mechanisms involved in the biotransformation are the 6'-N-methylation and the (4'-5')-reduction. The progression of the methylation was followed by the isotope technique, but the reduction reaction was not monitored.

Gentamicins↗
PubMed1976

Quantitative determination of factor-VIII protein by two-stage gel electrophoresis.

A new method for the quantification of factor-VIII protein in plasma is described which utilizes only commercially available equipment and material. The procedure involves separation of factor VII from other plasma proteins by a two-stage sodium dodecyl sulphate gel electrophoretic technique and quantification of the protein by scanning densitometry. The plasma from normal individuals, haemophiliacs, obligate carriers of haemophilia and patients with von Willebrand's disease have been examined by this technique. In general, the data support the earlier findings obtained by quantitative immunoelectrophoresis. In addition, some abnormalities not detected by immunoelectrophoresis are observed by the gel electrophoresis technique.

Electrophoresis, Agar Gel↗
PubMed1976

Formation of methylated and phosphorylated metabolites during the fermentation process of verdamicin.

In an attempt to understand the biosynthetic processes leading to the formation of verdamicin (end product), we have examined the patterns of the formation of methylated and phosphorylated metabolites, which resulted from either the addition of l-[methyl-(14)C]methionine or [(32)P]KH(2)PO(4) to the fermentation. Incorporation of label from l-[methyl-(14)C]methionine into the bioactive sisomicin, verdamicin, and the chromatographically polar components increased with the progression of time. Two methylated bioinactive metabolites were found in the culture broth after removal of the methylated bioactive metabolites. In contrast to the bioactive metabolites, incorporation of the methyl-(14)C label into the two methylated bioinactive metabolites decreased with the progression of time. A phosphorylated bioinactive metabolite (nonmethylated) was also found in the culture broth, fermented in the presence of [(32)P]KH(2)PO(4). The role of the phosphorylated metabolite in the biosynthesis of the bioactive metabolites cannot yet be explained.

Aminoglycosides↗
PubMed1976

Biological activity of netilmicin, a broad-spectrum semisynthetic aminoglycoside antibiotic.

Netilmicin (Sch 20569) is a new broad-spectrum semisynthetic aminoglycoside derived from sisomicin. Netilmicin was compared to gentamicin, tobramycin, and amikacin in a variety of in vitro test systems as well as in mouse protection tests. Netilmicin was found to be similar in activity to gentamicin against aminoglycoside-susceptible strains in both in vitro and in vivo tests. Netilmicin was also active against many aminoglycoside-resistant strains of gram-negative bacteria, particularly those known to possess adenylating enzymes (ANT 2') or those with a similar resistance pattern. Netilmicin was found to be markedly less toxic than gentamicin in chronic studies in cats, although gentamicin appeared less toxic in acute toxicity tests in mice. The concentrations of netilmicin and gentamicin in serum were compared in dogs after intramuscular dosing, and the pharmacokinetics including peak concentrations in serum were found to be similar.

Amikacin↗
PubMed1976

A new actinomycin complex produced by a Micromonospora species: fermentation, isolation, and characterization.

A species of Micromonospora, Micromonospora floridensis NRRL 8020, has been found to produce an actinomycin complex consisting of at least 25 active components. After solvent extraction of the complex, separation of the individual components was carried out by preparative thin-layer chromatography. Hydrolysis and subsequent electrophoretic and chromatographic identification of the amino acid content of each of the isolated components have shown differences from known actinomycins, and the probability exists that these contain a number of amino or imino acids not previously found in other members of this group of antibiotics.

Amino Acids↗
PubMed1976

A new broad spectrum aminoglycoside antibiotic, G-52, produced by Micromonospora zionensis.

G-52 is a new broad spectrum aminoglycoside produced by a species of the genus Micromonospora, Micromonospora zionensis. It has been differentiated from other known related antibiotics by a variety of chemical and biological methods. Its in vitro and in vivo spectrum of activity appears to be quite similar to that of verdamicin and gentamicin but is differentiated from them by its increased activity against 6'-N-acetylating strains.

Animals↗