Primary structure of aldehyde reductase from human liver.
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Alcohol Dehydrogenase↗
Biomedical subjects
M Wolf
Publications and source records attributed to M Wolf.
[Antithrombin III].
The in vivo regulation of coagulation is mainly controlled by plasma inhibitors in which antithrombin III (AT III) plays an importance role. AT III is a glycoprotein which inhibits all serine proteases, except factor, VIIa, generated during the coagulation process. The proteases are inactivated by formation of an equimolecular complex and this reaction is greatly enhanced in the presence of heparin. A similar catalytic process could occur in vivo, involving heparin-like substances present on the surface of the surface of the endothelial cell. The physiological importance of AT III is clearly demonstrated by the high incidence of thromboembolic disease in patients with congenital AT III défficiency.
Antithrombin III↗
[A simple procedure for CO detection in blood using micro-headspace gas chromatography].
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Carbon Monoxide↗
An enzyme immunoassay (ELISA) for the quantitation of human factor VII.
A new solid phase enzyme-linked immunosorbent assay (ELISA) was developed for the quantitation of human Factor VII antigen (F VII Ag), using a monospecific rabbit anti-F VII antiserum. Anti-F VII F(ab')2 fragments were adsorbed to polystyrene plates. The binding of serial dilutions of control or test plasma, containing F VII, was detected by incubation with peroxidase-labeled anti- FV II IgG followed by the addition of hydrogen peroxyde and O-phenylenediamine. This ELISA is specific, sensitive (detection limit: 0.05%) and accurate (coefficient of variation: 1.5-4% for within- and 1.6-9% for between-assays). F VII coagulant activity (F VII C) and F VII C) and F VII Ag were determined in large populations of controls and patients. In normal plasma (n = 38), F VII Ag ranged from 83 to 117% and the correlation coefficient between F VII Ag and F VII C was 0.94. In patients with severe (F VII C inf. 1%) congenital F VII deficiency (n = 5), F VII Ag was undetectable in two cases (inf. 0.05%) and markedly reduced (0.35 to 5.6%) in the three other cases. In patients with liver cirrhosis (n = 15), F VII Ag ranged from 21% to 59% and was in good correlation with F VII C (r = 0.84). In dicoumarol treated patients (n = 15), the levels of F VII Ag ranged from 51% to 79% and a poor correlation (r = 0.52) with F VII C was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibody Specificity↗
Postsynaptic densities contain a subtype of protein kinase C.
Protein kinase C or an isoenzyme thereof appears to be a significant component of postsynaptic densities (PSDs) from rat brain. This cytoskeletal organelle binds 4 beta-phorbol 12,13-dibutyrate (PDBu) with a Bmax of about 20 pmol/mg protein and an apparent Kd of 3.3 nM. Ca2+ and phosphatidyl serine (PS) stimulated the endogenous phosphorylation of a subset of PSD polypeptides with Mr values between 16,000 and 22,000. Finally, a monospecific protein kinase C antibody reacted with a Mr 70,000 PSD polypeptide which migrated on SDS-PAGE slightly ahead of the Mr 77,000 purified enzyme. These data suggest that protein kinase C or a similar enzyme can be integrated into a cytoskeletal system and may play an important role in postsynaptic function.
Animals↗
Protein kinase C and phosphatidylserine bind to Mr 110,000/115,000 polypeptides enriched in cytoskeletal and postsynaptic density preparations.
The selective binding of protein kinase C to nitrocellulose-immobilized polypeptides from rat brain and human erythrocytes was investigated. Bound enzyme was detected immunochemically with a monospecific protein kinase C antibody, or by using radiolabeled enzyme. Two polypeptides from erythrocyte membranes with Mr values of 110,000 and 115,000 bound protein kinase C in the presence of phosphatidylserine (PS) and were highly enriched in the cytoskeletal fraction. A prominent protein kinase C-binding polypeptide at Mr about 115,000 was also evident in brain cytoplasm, postsynaptic densities, and nuclei. Overlays of electrophoretic blots with 14C-phospholipids revealed that the protein kinase C-binding polypeptides also bound PS but not other phospholipids. The binding of both protein kinase C and PS was markedly inhibited after phosphorylation of the Mr 110,000/115,000 polypeptides with the kinase itself. The relevance of the results to the binding of protein kinase C to membranes and to phospholipid-cytoskeletal interactions is discussed.
Animals↗
Homozygous variant of antithrombin III: AT III Fontainebleau.
A qualitative defect of antithrombin III (AT III) was demonstrated in four members of a large Tunisian family by the discrepancy between a normal amount of antigen and decreased or absent heparin cofactor activity. The propositus, a 3-year-old girl, died from massive intracardiac thrombosis despite oral anticoagulant therapy. Heparin cofactor activity measured in the presence of thrombin or F. Xa was undetectable in her plasma. Anti-F. Xa activity was also absent when using low molecular weight heparin or a synthetic pentasaccharide, representing the binding site to AT III. The lack of affinity of the propositus AT III for heparin was demonstrated by two-dimensional immunoelectrophoresis and chromatography on heparin-Sepharose. The parents, first cousins, and the sister of the propositus also demonstrated a qualitative abnormality of AT III, with levels of heparin cofactor activity close to 50% of the normal range. Our data support the view that the abnormal protein was present at the heterozygous state in the parents and sister and at the homozygous state in the propositus. None of the affected family members had thrombotic episodes, except for the propositus. The name of AT III Fontainebleau is proposed for this variant.
Antithrombin III↗
Rapid alternating stimulus naming in the developmental dyslexias.
A rapid, alternating stimulus (RAS) naming measure was designed to study the developing ability in dyslexic readers to direct attention to contextual patterns while performing a rapid serial naming task. The results from a 3-year longitudinal investigation of 98 children indicate three trends. RAS performances differentiate both average from impaired readers and dyslexic subgroups from each other. The largest, most impaired subgroup can not complete the RAS tasks in kindergarten; the smaller subgroups have little name access speed deficits. Early RAS performances are highly predictive of later reading, particularly at the single-word reading level. Implications for understanding the development of automaticity and the relationship between retrieval speed and reading are discussed.
Child↗
Dyslexia, dysnomia, and lexical retrieval: a longitudinal investigation.
Results from a 3-year longitudinal investigation of confrontation naming in 98 children (75 average readers, 14 severely impaired readers, 9 bilingual readers) indicate: kindergarten performance on confrontation naming predicts Grade 2 reading performance, particularly reading comprehension; confrontation naming differentiates average from severely impaired readers; and lexical retrieval, not vocabulary knowledge, is the major source of difference between reading groups. Findings on lexical retrieval are integrated with research on naming access speed. The implications of these results for specification of dyslexia subgroups are discussed.
Anomia↗
Protein kinase C phosphorylates topoisomerase II: topoisomerase activation and its possible role in phorbol ester-induced differentiation of HL-60 cells.
DNA topoisomerase II from Drosophila was phosphorylated effectively by protein kinase C. With a Km of about 100 nM, the reaction was rapid, occurring at 4 degrees C as well as at 30 degrees C and requiring as little as 0.6 ng of the protein kinase per 170 ng of topoisomerase. About 0.85 mol of phosphate could be incorporated per mol of topoisomerase II, with phosphoserine as the only phospho amino acid produced. The reaction was dependent on Ca2+ and phosphatidylserine and was stimulated by phorbol esters. Calmodulin-dependent protein kinase II, but not cyclic AMP-dependent protein kinase, was also able to phosphorylate the topoisomerase. Phosphorylation of topoisomerase II by protein kinase C resulted in appreciable activation of the topoisomerase, suggesting that it may represent a possible target for the regulation of nuclear events by protein kinase C. This possibility is supported by the finding that the phorbol ester-induced differentiation of HL-60 cells was blocked by the topoisomerase II inhibitors novobiocin and 4'-(9-acridinylamino)methanesulfon-m-anisidide(m-AMSA), but not by the inactive analog o-AMSA.
Aminoacridines↗
Words created by children versus aphasic adults: an analysis of their form and communicative effectiveness.
The creation of words through the novel combination of English morphemes (e.g., "map ball" to refer to a globe) was studied in 40 preschool children, 40 grade school children, and 40 adults. These lexical innovations were collected while subjects named pictured objects, and were evaluated in terms of incidence, communicative effectiveness, novelty, semantic accuracy, and certain linguistic characteristics. Preschool children's innovations were as communicatively effective as those of grade school children and adults and contained the highest proportion of innovations with redundant elements. Grade school children produced the highest proportion with semantic inaccuracies. This suggests that preschoolers invent words from a limited set of highly familiar terms, whereas grade schoolers rely more on partially known terms. In addition, the children's innovations differed significantly from those previously collected from aphasic adults. This demonstrates that aphasia does not cause a regression to an early level of linguistic sophistication.
Anomia↗
A phase I-II study of cytosine arabinoside, daunorubicin, and VP16-213 in adult patients with acute non-lymphocytic leukemia.
The combination cytosine arabinoside (ara-C), daunorubicin, and VP 16-213 was studied in 28 patients with acute non-lymphocytic leukemia to define the toxicity of the combination and assess its efficacy. Of 21 previously untreated patients, 16 (76%) achieved a complete response (CR) with the median remission duration not reached but exceeding 25 weeks. For CR patients, the median number of days with neutrophils less than 500/microliter was 19. The median survival for patients with CR is 60 weeks. Two of seven previously treated patients achieved CR for 11 weeks and in excess of 36 weeks, respectively. At the initial VP16-213 dose of 100 mg m-2 per day for seven days, severe stomatitis was seen in 38% of courses but was less with dose reduction to 75 mg m-2 per day for seven days. Other toxicity was similar to previous experience with ara-C and daunorubicin alone.
Acute Disease↗
Automaticity, retrieval processes, and reading: a longitudinal study in average and impaired readers.
In this longitudinal investigation, the development of word-retrieval speed and its relationship to reading was studied in 72 average and 11 severely impaired readers in the kindergarten to grade 2 period (5-8 years). Subjects received a battery of 3 reading measures and 4 continuous naming tests with varied stimulus requirements. Results indicated that the relationship of retrieval speed to reading is a function of development and the correspondence between higher- and lower-level processes in the specific retrieval and reading measures. As automaticity in retrieval developed in average readers, naming-speed/reading relationships moved from strong, general predictions to highly differentiated ones. The strongest correlations were between naming speed for graphological stimuli and lower-level reading tasks. Impaired readers performed slower than average readers on all naming measures across all years, particularly on graphological symbols. 3 dyslexic subgroups emerged: the largest was globally impaired across all naming rate and reading tasks; 2 smaller subgroups had early specific, retrieval-rate deficits and dissociated reading deficits.
Child↗
Clinical and research training in parallel: the Internal Medicine Research Residency Track at the Brigham and Women's Hospital.
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Boston↗
[Measurement of objective parameters of image quality of film-screen combinations].
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Humans↗
Clinical application of a chromogenic substrate method for determination of factor VIII activity.
A chromogenic substrate kit for the determination of factor VIII activity (COATEST Factor VIII) has been evaluated in five different laboratories, one of them using a semi-automated procedure. This chromogenic method was compared to one-stage clotting assays for factor VIII determination in plasmas from healthy subjects, carriers of hemophilia A, severe, mild and moderate hemophilia A as well as von Willebrand's patients. In all these cases, a high correlation between these two methods was obtained (r = 0.96-0.99, n = 385) with a good agreement of the assigned potencies at all levels of factor VIII. A good correlation (r = 0.94) was also obtained for the levels of factor VIII after infusion of concentrates in six severe hemophiliacs or after administration of DDAVP to von Willebrand's patients. The chromogenic method is insensitive to preactivation of factor VIII by thrombin, thus yielding valid potency assignments also in these situations. The precision was higher with the chromogenic method than with the one-stage clotting assays (C.V. = 2-5% vs 4-15%). Altogether, the new chromogenic substrate method has proven itself suitable for determination of factor VIII in plasma and concentrates.
Blood Coagulation Tests↗
Interaction of protein kinase C with membranes is regulated by Ca2+, phorbol esters, and ATP.
Physiologic regulation of protein kinase C activity requires its interaction with cellular membranes. We have recently shown that binding of the enzyme to plasma membranes is controlled by Ca2+, whereas enzyme activators, like phorbol esters, regulate both membrane binding and enzyme activity. Here we describe the factors which control the dissociation of protein kinase C from the plasma membrane. In the absence of phorbol esters, the dissociation reaction is rapid and is determined by varying the Ca2+ concentration between 0.1 and 1 microM. However, the presence of 4-beta-phorbol 12,13-dibutyrate greatly reduces enzyme release in response to Ca2+ depletion; removal of the phorbol ester itself permits efficient membrane-enzyme dissociation. The stabilization of the membrane-protein kinase C complex by phorbol esters can be reversed by ATP with an apparent Km for the nucleotide of 6.5 microM. The ATP effect requires MgCl2 and cannot be reproduced by other nucleotides or by a nonhydrolyzable analogue, suggesting that an ATP-dependent phosphorylation reaction may be involved. 4-beta-Phorbol 12,13-dibutyrate appears to stabilize membrane-enzyme association by reducing the apparent Km for Ca2+ to about 15 nM, whereas ATP reverses the phorbol ester effect by increasing the Km for Ca2+ to about 760 nM. Furthermore, the strong degree of negative cooperativity displayed by the Ca2+-dependent enzyme-membrane dissociation is consistent with the presence of multiple interacting Ca2+-binding sites on protein kinase C.
Adenosine Triphosphate↗