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Biomedical subjects

D A Gabriel

Publications and source records attributed to D A Gabriel.

At least 55 records · Page 3Linked to original sources
PubMed1989

Calcium destabilizes and causes conformational changes in hyaluronic acid.

The physical properties of proteoglycans found in the extracellular matrix influence the behavior of resident macromolecules, micro-ions, and cells. The forces stabilizing structured regions of hyaluronic acid (HA), a major component of extracellular matrix, were measured. The free energy of stability associated with structured regions within human HA was determined by potentiometric titration. A plot of free energy versus temperature demonstrated that the secondary structure was most stable at 25 degrees C and was destabilized at temperatures near 50 degrees C. In the presence of 5 mM CaCl2, the free energy of stability of the structured regions was reduced by 30 cal/mole. Classical light scattering and viscosity measurements confirmed the impact of calcium on HA. CaCl2 (5 mM) reduced the radius of gyration of HA. Above concentrations of 3 mM calcium, the viscosity of 0.1% HA solutions was reduced sharply. The ability of cells to secrete calcium, combined with the exquisite sensitivity of HA to calcium, may permit cell-mediated modification of the extracellular matrix and thus may facilitate cell motility.

Calcium↗
PubMed1989

The clinical manifestations of Degos' syndrome.

Pathologic mechanisms underlying Degos' syndrome are poorly characterized. Thrombosis, either as a consequence of a postulated vasculitis or as a primary defect, is often a clinical complication of this syndrome. We have studied multiple coagulation parameters, including potential defects in fibrin assembly and other adhesive proteins, in a patient with Degos' syndrome and found no specific abnormality to explain the pathologic features of this syndrome. An extensive literature review as well as detailed biochemical and biophysical coagulation studies are presented. The alternative possibility of Degos' syndrome as a mucinosis is discussed.

Adolescent↗
PubMed1988

Influence of the subendothelial basement membrane components on fibrin assembly. Evidence for a fibrin binding site on type IV collagen.

Effective repair of a vascular injury depends on establishment of a stable fibrin patch at the injury site. Data presented in this study demonstrate that structural modification of fibrin occurs as a result of fibrin interaction with naturally occurring components of the vascular basement membrane and subendothelial structures. Of the basement membrane components, type IV collagen produces the greatest structural modification, generating thick fibrin fibers; a 3-fold increase in the fiber mass/length ratio occurs when type IV collagen is increased from 0 to 100 ng/ml. Laminin and dermatan sulfate decrease the fibrin fiber mass/length ratio resulting in thinner fibers. However, the overall effect of the basement membrane on fibrin is to increase the fibrin fiber diameter. Electrophoretic light scattering and the binding of type IV collagen by fibrinogen-Sepharose further establish the interaction between type IV collagen and fibrinogen. Incorporation of laminin with type IV collagen onto coated surfaces decreases the ability of type IV collagen to bind fibrinogen. These studies emphasize that the final fibrin structure is influenced by the milieu in which the clot is assembled.

Basement Membrane↗
PubMed1988

The use of high-dose intravenous gamma-globulin in acquired von Willebrand syndrome.

Acquired von Willebrand syndrome has been reported in patients with a variety of primary diseases, many immunologic in nature. Usually, an autoantibody to von Willebrand factor can be identified. These patients often experience severe hemorrhages requiring large doses of cryoprecipitate or factor VIII concentrates, thus exposing them to viral and allergic complications. The success of intravenous gamma-globulin in the treatment of other autoimmune diseases prompted us to treat two patients with acquired von Willebrand syndrome with high-dose intravenous gamma-globulin. Two days after initiation of therapy, von Willebrand factor and factor VIII rose to normal levels in both patients. Patient 1 underwent dental surgery, and patient 2 underwent a splenectomy without increased bleeding and without additional factor coverage or desmopressin acetate therapy. Thus, intravenous gamma-globulin is efficacious for acquired von Willebrand syndrome and obviates the need for replacement therapy with its attendant complications.

Aged↗
PubMed1988

Nonsecretory multiple myeloma.

A diagnosis of nonsecretory multiple myeloma, based on multiple bony lytic lesions seen on roentgenographic studies and sheets of plasma cells seen in the bone marrow, was established in two patients with severe back pain. No paraprotein was detected in the serum or concentrated urine of the patients. Immunofluorescent staining of the bone marrow demonstrated the presence of intracytoplasmic J chains in the patients' plasma cells.

Bone Marrow↗
PubMed1987

Platelet factor 4 enhances fibrin fiber polymerization.

In order to further examine the role of platelet secretory products on fibrin assembly, we have examined the effects of purified platelet factor 4 (PF4) on fibrin formation in vitro. The kinetics of fibrin formation and the structural properties of the resulting fibrin gel are strongly affected by PF4. In the presence of 7.6 ng/mL PF4, the fibrin fiber mass-length ratio increases from 3.5 X 10(12) daltons/cm. These results emphasize the importance of the local microenvironment in clot structure and its subsequent fate at the site of vascular injury.

Fibrin↗
PubMed1987

Spontaneous antithrombin in a patient with benign paraprotein.

A 66-year-old man with peptic ulcer disease developed a paraprotein that resulted in a spontaneously prolonged prothrombin time, activated partial thromboplastin time, and thrombin clotting time. Although the reptilase time was normal, the thrombin clotting time failed to correct with the addition of normal plasma, calcium, or protamine sulfate. The patient's purified fibrinogen was normal, but his serum contained an IgG that inhibited the clotting of normal plasma and purified fibrinogen in the presence of thrombin. In contrast to previously described paraproteins, this patient's IgG appeared to inhibit the activity of thrombin per se rather than to interfere with fibrinogen cleavage or fibrin polymerization. Although immunoprecipitation between thrombin and the paraprotein could not be demonstrated, the patient's purified IgG, in the presence of thrombin, decreased the thrombin activity on a chromogenic substrate. Further, increasing concentrations of thrombin overcame the inhibitory effect of the patient's paraprotein. Thus, the patient's paraprotein appeared to possess antithrombin activity.

Aged↗
PubMed1987

Influence of factor XIII and fibronectin on fiber size and density in thrombin-induced fibrin gels.

The possible role of fibronectin as a molecular anchor for fibrin to ground substance, the ability of factor XIII to cross-link fibronectin to fibrin, and the demonstrated differences between purified fibrin and fibrin formed in plasma prompted this study of the effect of both proteins on fibrin assembly and structure. The influences of activated factor XIII (FXIIIa) and fibronectin were studied by use of turbidity techniques. Fibronectin over a concentration range of 0 to 800 micrograms/ml produced no change in either the mass-length ratio or density of fibrin fibers in 1 mg/ml fibrin gels. FXIIIa at concentrations as high as 6.5 mumol/L, although not altering fiber mass-length ratio, caused a 30% increase in fiber density. Gels formed in the presence of fibronectin plus FXIIIa demonstrated increasing fiber mass-length ratios and increasing fiber density with increasing fibronectin concentration. Mass-length ratios for gels formed in the presence of 3.24 mumol/L FXIIIa increased from 3.25 to 5.20 x 10(13) daltons/cm as the fibronectin concentration increased from 0 to 800 micrograms/ml. Fiber density increased from 13.6 to 19.1 x 10(22) daltons/cm3 over the same fibronectin range. These results imply that FXIIIa-induced structural changes such as increased elastic modulus may be mediated in part by increased fiber density. Fibronectin alone has virtually no impact on fibrin assembly, but in the presence of FXIIIa becomes incorporated into fibrin and results in increased fiber size and density.

Chemical Phenomena↗
PubMed1986

Influence of Ca2+ on the structure of reptilase-derived and thrombin-derived fibrin gels.

The effects of Ca2+ ion on the structure of thrombin-derived and reptilase-derived fibrin gels formed at various ionic strengths were studied turbidimetrically. For both enzymes clotting times were shorter, final gel turbidities were higher and fibre mass/length ratios were increased as the ionic strength was lowered. The addition of 5 mM-Ca2+ augmented each of these effects for any given ionic strength. In the thrombin system, Ca2+ increased the final gel turbidity from 0.04 to 0.26 A632.8 at ionic strength 0.15. Under identical conditions in the reptilase system, the final gel turbidity increased from 0.03 A632.8 in the absence of Ca2+ to 0.345 A632.8 in the presence of 5 mM-Ca2+. In the thrombin system, fibre mass/length ratios increased from 0.4 X 10(12) to 6.9 X 10(12) Da/cm in the absence of Ca2+, and from 4.4 X 10(12) to 7.9 X 10(12) Da/cm in the presence of Ca2+, as the ionic strengths were decreased from 0.15 to 0.08 and to 0.11 respectively. In the reptilase system, the mass/length ratios increased from 0.9 X 10(12) to 5.8 X 10(12) Da/cm in the absence of Ca2+, and from 4.8 X 10(12) to 8.7 X 10(12) Da/cm in the presence of Ca2+, as the ionic strengths were decreased from 0.15 to 0.08 and to 0.10 respectively. At ionic strengths below 0.10, the presence of 5 mM-Ca2+ caused precipitation and macroscopic aggregation of fibrinogen upon the addition of either enzyme. In the presence of 5 mM-Ca2+, the fibres composing thrombin-induced and reptilase-induced gels were virtually identical.

Batroxobin↗
PubMed1986

Oophoropexy and the management of Hodgkin's disease. A reevaluation of the risks and benefits.

Female patients with Hodgkin's disease who undergo staging laparotomy frequently have oophoropexy performed to preserve both fertility and hormone production. Because of recent changes in therapy favoring systemic chemotherapy rather than total nodal irradiation for patients with stage III Hodgkin's disease, the need for oophoropexy may be less than previously described. Thirty-nine women of childbearing age underwent laparotomy at the University of North Carolina, Chapel Hill, from 1970 to 1984. Twenty-seven patients underwent oophoropexy. Only three of these patients would have needed this procedure based on their subsequent therapy. Two patients required additional gynecologic surgery because of complications related to the oophoropexy. The success rate in preservation of menstrual function and fertility is also discussed. We review the previous experience with oophoropexy and suggest an alternative approach to the routine use of this procedure.

Abdominal Muscles↗
PubMed1986

Hyperfibrinogenemia as a cause of prolonged thrombin clotting time.

Recognized causes of a prolonged thrombin clotting time (TCT) include a decreased plasma fibrinogen level, dysfibrinogenemia, paraproteinemia, heparin contamination, elevated levels of fibrin degradation products, and liver failure. We have frequently seen patients with an isolated prolonged TCT in the absence of any of these conditions and without obvious clinical impact. During a previous evaluation of hyperfibrinogenemia, we noted a surprisingly high incidence of prolonged TCT, prompting this evaluation of hyperfibrinogenemia as a possible cause. In our prospective study nine patients had a TCT more than 3 seconds longer than a matched control subject's TCT, with simultaneously normal prothrombin and activated partial thromboplastin times. Eight patients had fibrinogen levels more than 100 mg/dl above the control level (range 383 to 1,223 mg/dl). Only one patient's prolonged TCT could be explained on the basis of elevated levels of fibrin degradation products. In vitro studies in both a purified fibrinogen system and in plasma confirmed a delay in TCT with increasing initial fibrinogen concentrations. Kinetic measurements demonstrated a slowing of the normal initial increase in turbidity seen upon the addition of thrombin. Possible explanations include binding of thrombin to fibrin, or interference with fibrin assembly by excess fibrinogen. Regardless of the kinetic explanation, isolated prolongations of TCT due to hyperfibrinogenemia appear to be of minimal clinical significance.

Adult↗
PubMed1986

Granulocyte lysosomal cationic protein alters fibrin assembly: a possible mechanism for granulocyte control of clot structure.

The effect of highly positively charged molecules on the assembly and structure of thrombin-induced fibrin gels was studied with turbidity techniques. Lysosomal cationic proteins (LCP) extracted from rabbit heterophils produced enhanced lateral association of fibrin fibers. A crude extract of LCP had little effect on kinetics but produced an increase in the final fiber mass/length ratios. A purified fraction, LCP-5, of the crude extract enhanced both the initial rate of increase and final turbidity of fibrin gels. Mass/length ratios obtained for fibrin fibers as a function of LCP-5 concentration varied from 4.3 X 10(12) in the absence of LCP-5 to 7.8 X 10(12) daltons/cm at 1 microgram LCP-5/ml. Similar studies were conducted with protamine as the perturbant of fibrin assembly. Mass/length ratios were increased from 5.7 X 10(12) daltons/cm with no protamine to 8.5 X 10(12) daltons/cm at 100 micrograms protamine per milliliter. High concentrations of both LCP and protamine precipitated fibrinogen. This phenomenon may imply a mechanism by which the blood cellular components may modulate clot structure through the release of highly charged molecules such as LCP-5.

Animals↗
PubMed1985

Tracer diffusion coefficients of proteins by means of holographic relaxation spectroscopy: application to bovine serum albumin.

Holographic relaxation spectroscopy has been used to measure tracer diffusion coefficients for photochromically labeled bovine serum albumin in solutions having total bovine serum albumin concentrations in the range 3.25 to 257 g/liter. In the limit of zero concentration, the diffusion coefficient (20 degrees C, 0.1 M NaCl, 0.05 M Tris, pH 8.0) was found to be (5.9 +/- 0.1) X 10(-7) cm2/s and the initial slope was zero. The concentration dependence of the diffusion coefficient was not significantly affected by the fraction of protein molecules which were labeled. Holographic relaxation spectroscopy permits rapid, accurate determination of tracer diffusion coefficients for proteins in mixtures.

Animals↗
PubMed1985

Nasal packing with porcine fatty tissue for epistaxis complicated by qualitative platelet disorders.

Medications and renal failure are common causes of qualitative platelet disorders. Epistaxis occurring in these settings may be unresponsive to conventional therapy. Two patients with epistaxis and platelet dysfunction are presented who were successfully treated with porcine nasal packing. The technique, previously shown effective in thrombocytopenic patients, is inexpensive, simple, and effective. The procedure is described and its possible modes of action are discussed. The pathogenesis of platelet disorders induced by uremia and aspirin are also briefly discussed.

Adipose Tissue↗
PubMed1985

Viscous factors in peripheral tissue perfusion.

To ascertain the relative importance of the factors that influence blood viscosity (VIS), we measured hematocrit (HCT), filterability index, fibrinogen level (FIB), and Ektacytometer indices at osmolarities of both 290 (EI 290) and 200 (EI 200) in 21 diabetic patients with peripheral vascular disease (DPVDs) and 11 healthy volunteers (HVs). Stepwise multiple regression analyses generated a formula based on three of the independent variables (FIB, HCT, EI 200) that accurately predicted VIS (r = 0.79, p less than 0.01). Based on the beta coefficients and F statistics, HCT and FIB were the most important elements in the linear regression equation. Compared with HVs the total group of DPVDs had lower HCT (36.5% vs. 42.4%) and higher FIB (661 vs. 276 mg/dl, p less than 0.01) values. When all HVs were compared with a subgroup of DPVDs with similar HCT (n = 10), both FIB and VIS were higher (p less than 0.001) in the DPVD than in the HV group. We conclude that the most important of the multiple factors that influence VIS are HCT and FIB. The finding of increased FIB in DPVDs could have important implications for drug and surgical therapy in this group of patients.

Blood Circulation↗
PubMed1983

Dye binding probes of lipid-binding structures. An investigation of 2-p-toluidinylnaphthylene-6-sulfonate binding to human and bovine prothrombin and fragment 1 in the presence and absence of calcium and magnesium ions.

TNS (2-p-toluidinylnaphthylene-6-sulfonate) binds to human and bovine prothrombin and Fragment 1 in the absence and presence of added Ca2+. The stoichiometry of TNS binding is 1:1 for human and bovine prothrombin and Fragment 1. The Ca2+-dependence of the fluorescence of TNS bound to bovine prothrombin Fragment 1 yields a modified Hill plot slope of 2.7, which is consistent with the slope obtained by monitoring the Ca2+ dependence of protein fluorescence quenching, CD changes and phospholipid binding. Mg2+ has have no effect on the fluorescence of TNS-prothrombin fluorescence. TNS binding to the amino-terminal region of prothrombin is the first relatively simple probe of the subtle and complex relationship which exists between protein structure and phospholipid binding.

Animals↗