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B Brenner

Publications and source records attributed to B Brenner.

At least 19 recordsLinked to original sources
PubMed1992

Effect of Ca2+ on weak cross-bridge interaction with actin in the presence of adenosine 5'-[gamma-thio]triphosphate).

In the presence of the nucleotide analog adenosine 5'-[gamma-thio]triphosphate (ATP[gamma S]), effects of Ca2+ on stiffness and equatorial x-ray diffraction patterns of single skinned fibers of the rabbit psoas muscle were studied. It is shown that cross-bridges in the presence of ATP[gamma S] have properties of the weak-binding states of the ATP hydrolysis cycle. Raising the Ca2+ concentration up to pCa 4.5 has little effect on actin affinity of cross-bridges in the presence of ATP[gamma S]. However, the rate constants for cross-bridge dissociation and reassociation from and to actin are reduced by about 2 orders of magnitude. In addition, nucleotide affinity of the cross-bridge is much smaller at high Ca2+ concentrations. Implications for interpretation of fiber stiffness recorded during isotonic shortening and the rising phase of a tetanus are discussed.

Actins↗
PubMed1992

Characterization of three mutations causing von Willebrand disease type IIA in five unrelated families.

Von Willebrand disease (vWD) type IIA is characterized by decreased ristocetin-induced platelet aggregation, and by the absence from plasma of high molecular weight multimers of von Willebrand factor (vWF). Most mutations causing vWD type IIA are clustered within the A2 domain of the mature vWF subunit that is encoded by exon 28. Using the polymerase chain reaction (PCR), the entire exon 28 from patients with vWD type IIA and normal controls was amplified and sequenced. Three missense mutations were detected that result in the amino acid substitutions were detected that result in the amino acid substitutions Arg(834)----Trp, Gly(742)----Glu, and Ser(743)----Leu. The first mutation occurred independently in three unrelated families; each of the latter mutations was found in one family. By restriction endonuclease analysis and allele-specific oligonucleotide (ASO) hybridization the mutations were confirmed in affected family members and excluded in unaffected members and 50 normal controls. The apparently high frequency of identical independent mutations among patients with vWD type IIA suggests that a precise diagnosis may be possible in a majority of patients using relatively simple recombinant DNA screening assays.

Alleles↗
PubMed1992

Studies on the effect of two angiotensin-converting enzyme inhibitors, captopril and cilazapril, on platelet and vascular prostaglandin metabolism in vivo.

We have studied in 12 healthy volunteers the effects of two angiotensin-converting enzyme (ACE) inhibitors, captopril and cilazapril, on vascular and platelet prostaglandin metabolism, in a double-blind, placebo-controlled, randomized cross-over study. Formation of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TxB2) was measured locally at the site of a microvascular injury. Similar amounts of TxB2 and 6-keto-PGF1 alpha were generated following administration of either ACE inhibitor as compared to placebo. It is concluded that neither captopril nor cilazapril significantly influence vascular and platelet prostaglandin metabolism.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Cardiac involvement in patients with myeloproliferative disorders.

INTRODUCTION: To evaluate cardiac involvement in myeloproliferative disorders (MPD), two-dimensional and Doppler echocardiographic studies were performed in 30 patients with MPD. PATIENTS AND METHODS: There were 18 women and 12 men, with an age range from 35 to 76 years. Eighteen patients had polycythemia vera (PV), 8 had essential thrombocythemia (ET), and 4 had agnogenic myeloid metaplasia (AMM). RESULTS: Echocardiography revealed valvular lesions in 19 of 30 patients (63%) compared with only 1 of 22 patients (4.5%) in a control group of patients referred for echocardiography to exclude a cardiac source for idiopathic systemic thromboembolism (chi 2 = 13.39, p < 0.001, by chi 2 test with Yates' correction). Valvular lesions were found in 77% of patients with PV, 50% with ET, and 25% with AMM (p = NS). The aortic and mitral valves were the most commonly involved valves, and the most common echocardiographic lesion was leaflet thickening, which was found in 12 patients (40%), followed by vegetations, which were observed in 5 patients (16%). In their past history, 14 of 30 (47%) MPD patients had arterial or venous thrombosis or embolism. Twelve of 19 (63%) patients with valvular lesions had thromboembolism compared with only 2 of 11 (18%) patients without evidence of valvular lesions (chi 2 = 3.99, p < 0.05, by chi 2 test with Yates' correction). Pulmonary hypertension, unrelated to the severity of valvular disease and probably resulting from pulmonary venous occlusion, was found in four patients (13%). CONCLUSIONS: We conclude that the heart is frequently involved in patients with MPD, particularly when their past history is complicated by a thromboembolic event. Some patients have clinically significant valvular disease. Pulmonary hypertension is another relatively common finding in MPD patients. Echocardiography provides information of clinical significance in MPD patients. A larger number of patients is needed to determine whether the presence of valvular lesions is of prognostic significance and may herald future thromboembolic events.

Adult↗
PubMed1992

Circumcision in hemophilia: the use of fibrin glue for local hemostasis.

Circumcision can be fatal in hemophilia patients unless they are treated with the missing coagulation factor. We describe 10 severe hemophilia patients in whom circumcision was performed with local fibrin glue instead of infusion of factor concentrate. Of the 10 patients 3 had postoperative bleeding and only 2 of them required infusion of factor VIII concentrate. Fibrin glue is a useful treatment modality for circumcision in patients with bleeding diathesis, and it is safer and cheaper than the infusion of factor concentrate.

Adolescent↗
PubMed1992

Angiosarcoma of the colon developing in a capsule of a foreign body. Report of a case with associated hemorrhagic diathesis.

A case of angiosarcoma of the colon is reported. The tumor developed in the fibrous capsule of a retained sponge that was lost 25 years earlier during a gynecologic surgical procedure. The postoperative course was dominated by a fatal consumptive thrombohemorrhagic disorder. Angiosarcoma associated with a retained foreign body and development of hemorrhagic diathesis in angiosarcoma are discussed.

Aged↗
PubMed1992

High incidence of myeloproliferative disorders in Ashkenazi Jews in northern Israel.

We have analysed epidemiological parameters in 339 patients with myeloproliferative disorders (MPD) diagnosed in northern Israel between 1975 and 1989 as having polycythemia vera (191 patients), agnogenic myeloid metaplasia (AMM) (113) and essential thrombocythemia (ET) (36). Mean average annual incidence was 11.4 per 1 million residents for polycythemia vera, 6.5 for AMM and 2.1 for ET. For all three diseases the average annual incidence increased with age and was 10 times higher in patients over 65 years compared to those less under the age of 45 years. Four percent of all patients had relatives with MPD. Incidence of MPD in Jews was 10 fold higher than expected compared to Arabs and this difference was noted for all 3 diseases. The incidence in Ashkenazi Jews originating from eastern and central Europe, was 10 and 20 folds higher than in Sephardic Jews and Arabs respectively. Mean age at diagnosis of MPD in Arabs and Sephardic Jews was lower than in Ashkenazi Jews (52 and 56 years compared to 64 years P < 0.05). Likewise, mean age at diagnosis was lower in the 11.5% of MPD patients with prior exposure to biological or chemical hazards compared to unexposed individuals (58 years versus 63 years, P < 0.02). These data demonstrate a cluster of MPD in Ashkenazi Jews in northern Israel and emphasize the importance of genetic predisposition possibly interacting with acquired factors in the pathogenesis of these disorders.

Adult↗
PubMed1992

RNA polymerase chain reaction detects different levels of four alternatively spliced WT1 transcripts in Wilms' tumors.

A Wilms' tumor susceptibility gene (WT1) localized to 11p13 was recently isolated and shown to be altered in some sporadic Wilms' tumors. This gene encodes a DNA-binding protein with four zinc fingers (ZFs) in the carboxy-terminal region and a glutamine/proline (Gln/Pro)-rich domain near the 5' end. Two alternative splice sites were described, splice I in the Gln/Pro-rich domain (51 bp) and splice II between ZFs 3 and 4 (9 bp). Using RNA polymerase chain reaction (PCR) we show that Wilms' tumors contain all four possible transcripts, which are also identified in normal adult and embryonic kidney cells. The transcripts containing the 9-bp ZF insert were always predominant in tumors and normal cells. The presence of all four WT1 transcripts in tumors and expressing tissues suggests that each encoded protein isoform has an important role for the function of the WT1 gene.

Adult↗
PubMed1992

Dental surgery in patients with severe factor XI deficiency without plasma replacement.

Bleeding following dental extraction is frequently the first manifestation of severe factor XI deficiency. Safe oral surgery has previously been performed in such patients by using plasma replacement therapy with or without concomitant administration of antifibrinolytic agents. The aim of this study was to determine whether such patients can undergo safe dental extractions using only an antifibrinolytic agent. The study group consisted of 19 patients with severe factor XI deficiency (factor XI:C level less than 14 U/dl) who had previously bled following dental extractions (14 patients) or other trauma (five patients). Tranexamic acid, 1 g q.i.d., was given from 12 h before surgery, until 7 days afterwards. No excessive bleeding was observed following dental extractions. One patient had slight oozing after 3 days which ceased spontaneously. Thus, plasma replacement no longer appears necessary for patients with severe factor XI deficiency requiring dental extractions.

Adult↗
PubMed1992

Fatal hemoperitoneum after fine-needle aspiration of a liver metastasis.

Fine-needle aspiration (FNA) of the liver is a procedure considered virtually risk-free. We report here a patient with carcinoma of the pancreas, who suffered a fatal hemoperitoneum (HP) subsequent to FNA of the liver under the guidance of ultrasound. The patient had presented with migratory deep vein thrombosis (DVT), and recurrent cerebral embolism. The prothrombin time (PT) and partial thromboplastin time (PTT) had been normal, and FNA demonstrated adenocarcinoma cells. Autopsy findings demonstrated carcinoma in the tail of the pancreas with liver and adrenal metastases, massive HP, and findings of chronic disseminated intravascular clotting (DIC). Since chronic DIC with enhanced fibrinolysis might have participated in the fatal bleeding, we recommend that FNA should be contraindicated in patients suspected of having malignancy with migratory DVT and recurrent arterial embolism, despite normal PT and PTT tests, unless the appropriate laboratory tests succeed in excluding DIC.

Adenocarcinoma↗
PubMed1992

Comparison of dosage schedules of rt-PA in the treatment of proximal deep vein thrombosis.

This study assessed the efficacy and safety of increasing durations of constant-dose intravenous recombinant tissue-type plasminogen activator (rt-PA) in the treatment of deep vein thrombosis. Patients with venogram-documented proximal lower limb (popliteal, iliofemoral) or upper limb (axillary, subclavian) thrombi were given an initial 2-hour rt-PA infusion at 4 micrograms/kg/min, followed by a maintenance infusion of 1 microgram/kg/min for an additional 4, 22, or 33 hours (mean total rt-PA dosages of 54, 127, and 185 mg). A new quantitative venogram scoring system was applied to the study, based on measurements of thrombus volume before and after completion of treatment. Whereas none of the seven patients given treatment for 6 hours and only one of four given treatment for 24 hours showed significant lysis, four of seven who received a prolonged infusion for 35 hours showed lysis of more than 40% of the original thrombus. Overall, the prolonged 35-hour infusion induced 51% lysis of original thrombus, representing a thrombus volume of 16.7 ml dissolved. Hemorrhagic complications were common in all three groups, with four of 18 patients having significant bleeding, including one massive gastrointestinal hemorrhage, two patients with a decrease in hematocrit of more than 10%, and one patient with an intracranial hemorrhage who recovered completely. Pharmacokinetics of the rt-PA showed a steady state antigen concentration of 240 ng/ml and activity of 200 IU/ml during the initial 2-hour infusion and a postinfusion half-life of 5 minutes. Plasma fibrinogen concentrations decreased to approximately 40% to 50% of initial values with all three treatment regimens, but the nadir fibrinogen concentrations did not correlate with either therapeutic efficacy or bleeding complications. One patient with systemic lupus erythematosus had an unusual allergic reaction that manifested primarily as angioedema. This study suggests that rt-PA infusion of 35 hours induces greater thrombolysis of deep vein thrombosis than does a shorter course of 6 or 24 hours, without an increase in hemorrhagic complications.

Adult↗
PubMed1992

Association of lupus anticoagulant and anticardiolipin antibodies with thrombosis in patients with systemic lupus erythematosus, primary antiphospholipid syndrome and other disorders.

Lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) have been associated with thrombotic events and recurrent fetal loss. In order to assess the role of LA with the thrombotic tendency in various disease states we evaluated 38 patients with confirmed LA [tissue thromboplastin index (TTI) greater than 1.3; circulating anticoagulant index (CAI) greater than 15], subgrouped as follows: a) LA associated with systemic lupus erythematosus (SLE) (n = 13); b) primary antiphospholipid syndrome (PAPS) (n = 16); and c) LA associated with other disorders (n = 9). Male/female ratio differed between the groups: 0/13, 6/10 and 4/5, respectively. Venous and arterial thrombotic events were more common in the PAPS group (87%) compared with the SLE group (61%) and the other disorders group (22%). Serum ACA antiphospholipid IgG levels by ELISA were increased in the SLE and PAPS patients, but did not differ between the groups (167 +/- 24 vs. 190 +/- 28 mu respectively). Antiphospholipid IgM levels were higher in the SLE group compared with the PAPS group (127 +/- 15 vs. 67 +/- 16 mu). Mean TTI and CAI levels did not differ between the SLE, PAPS and other disorders groups (1.8 +/- 0.19, 2.8 +/- 0.9, 2.0 +/- 0.3 for TTI; 25 +/- 4, 33 +/- 4, 32 +/- 5 for CAI). Likewise TTI, CAI and ACA levels did not differ in patients with or without thrombosis. We conclude that the prevalence of thrombotic manifestations varies among patients with similar serum intensities of LA and levels of ACA, suggesting that other factors may be involved in the pathogenesis of thrombosis in these patients.

Adult↗
PubMed1991

Rapid dissociation and reassociation of actomyosin cross-bridges during force generation: a newly observed facet of cross-bridge action in muscle.

The force response of skinned fibers of the rabbit psoas muscle to stretches (and releases) was studied. At physiological ionic strength and low experimental temperature (5 degrees C) the force response to stretches apparently is affected neither by cross-bridges that occupy weak-binding states nor by transitions among various attached force-generating states. Plots of force vs. imposed length change (T plots) recorded during stretches suggest that cross-bridges even in force-generating states dissociate and reassociate rapidly from and to actin as had previously been proposed [Brenner, B. (1986) Basic Res. Cardiol. 81, 1-15]. Plots of fiber stiffness vs. speed of imposed length changes (stiffness-speed relations) imply rate constants for dissociation (k-) in the force-generating states ranging from 50 to 1000 s-1, while the rate constant for reassociation (k+) has to be at least an order of magnitude larger (high actin affinity). Rapidly reversible actin interaction of cross-bridges in force-generating states provides a mechanism for rapid detachment of force-generating cross-bridges during high-speed shortening which, in contrast with the hypothesis of A. F. Huxley [(1957) Prog. Biophys. 7, 255-318], and related cross-bridge models, does not require completion of the ATP-hydrolysis cycle and thus may account for the unexpectedly low ATPase activity during high-speed shortening.

Actomyosin↗
PubMed1991

Parallel inhibition of active force and relaxed fiber stiffness in skeletal muscle by caldesmon: implications for the pathway to force generation.

In recent hypotheses on muscle contraction, myosin cross-bridges cycle between two types of actin-bound configuration. These two configurations differ greatly in the stability of their actin-myosin complexes ("weak-binding" vs. "strong-binding"), and force generation or movement is the result of structural changes associated with the transition from the weak-binding (preforce generating) configuration to strong-binding (force producing) configuration [cf. Eisenberg, E. & Hill, T. L. (1985) Science 227, 999-1006]. Specifically, in this concept, the main force-generating states are only accessible after initial cross-bridge attachment in a weak-binding configuration. It has been shown that strong and weak cross-bridge attachment can occur in muscle fibers [Brenner, B., Schoenberg, M., Chalovich, J. M., Greene, L. E. & Eisenberg, E. (1982) Proc. Natl. Acad. Sci. USA 79, 7288-7291]. However, there has been no evidence that attachment in the weak-binding states represents an essential step leading to force generation. It is shown here that caldesmon can be used to selectively inhibit attachment of weak-binding cross-bridges in skeletal muscle. Such inhibition causes a parallel decrease in active force, while the kinetics of cross-bridge turnover are unchanged by this procedure. This suggests that (i) cross-bridge attachment in the weak-binding states is specific and (ii) force production can only occur after cross-bridges have first attached to actin in a weakly bound, nonforce-generating configuration.

Actins↗