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Biomedical subjects

H R Gralnick

Publications and source records attributed to H R Gralnick.

At least 127 records · Page 7Linked to original sources
PubMed1980

Selective binding of the factor VIII/von Willebrand factor protein to human platelets.

The factor VIII/von Willebrand factor protein was radiolabeled after modification by galactose oxidase and reduction with tritiated potassium borohydride. This mild efficient method for labeling resulted in retention of over 90% of the biologic activities of the factor VIII/von Willebrand factor protein. Binding of this protein to platelets was found to be specific, and binding sites could be saturated in the presence of ristocetin. However, binding was highly dependent on ristocetin concentration, as the number of human factor VIII/von Willebrand factor molecules bound per platelet was a function of the ristocetin concentration. At a ristocetin concentration of 0.55 mg/ml, each platelet binds approximately 11,000 factor VIII/von Willebrand factor molecules per platelet. Scatchard analysis of the concentration-dependent binding sites yielded a hyperbolic plot that appeared to be related to the existence of two classes of binding sites. The higher affinity class had a Kd of 3.7 x 10(-10) M 3500 sites/platelet, while the lower affinity class had a Kd of 2.35 x 10(-9) M and a capacity of 7500 sites/platelet. As with ristocetin-induced platelet agglutination, the carbohydrate content plays a significant role in the binding of the factor VIII/von Willebrand factor protein to the platelet.

Antigens↗
PubMed1979

Acute nonlymphocytic leukemia and acute myeloproliferative syndrome following radiation therapy for non-Hodgkin's lymphoma and chronic lymphocytic leukemia: clinical studies.

Seven cases of acute nonlymphocytic leukemia (ANLL) and one case of a malignant myeloproliferative syndrome have been seen after extensive radiation therapy for non-Hodgkin's lymphoma or chronic lymphocytic leukemia. A myeloproliferative syndrome with abnormalities in granulocytic, erythrocytic, and thrombocytic cell lines was present in all patients and in seven patients preceded ANLL by 2--18 months. The median time to the development of ANLL after primary disease therapy was 61 months (33--98 range). The leukemia was extremely refractory to therapy and median survival after diagnosis of ANLL was two months (range 0--9 months). Leukemia was seen only in those patients who received multiple courses and multiple techniques of radiation therapy.

Adult↗
PubMed1979

Whole body hyperthermia: a phase-I trial of a potential adjuvant to chemotherapy.

Fourteen patients with a variety of neoplasms not responsive to standard forms of therapy underwent whole body hyperthermia for a maximum 4 h at 41.8 degrees C. This was a phase-I cancer trial designed to develop whole body hyperthermia as an adjuvant to systemic chemotherapy. Intravenous analgesia was used to sedate patients, obviating the need for general endotracheal anesthesia. Hyperthermia was induced by means of a high-flow water perfusion suit. Cardiovascular performance was evaluated using a flow-directed pulmonary artery catheter. Patients developed a twofold mean increase in cardiac index without evidence of cardiac damage by ECG or creatine phosphokinase (CPK) isoenzymes. An acute fall in serum magnesium and phosphate and an acute rise in arterial pH, serum CPK values, and granulocyte count occurred in all patients. There were no clotting abnormalities. Toxicity included fatigue, diarrhea, nausea, and transient elevations in liver enzymes. Four patients were febrile for 36 h after initial defervescence. Peripheral neuropathy developed in four. These results show that with carefully monitored conditions whole body hyperthermia is feasible.

Adolescent↗
PubMed1979

The hemostatic imbalance of plasma-exchange transfusion.

Plasma exchange has been proposed as a treatment for multiple disorders. Three patients with amyotropic lateral sclerosis, who were hemostatically normal, were studied through a total of 11 4-liter exchanges. Plasma was replaced by an equal volume of 5% albumin or 5% plasma protein fraction. Serial studies revealed that immediately after the exchange transfusion, there was significant prolongation of the prothrombin, partial thromboplastin, and thrombin times with reduction of the fibrinogen and antithrombin III levels. Factors V, VII-X, IX, and X were all significantly decreased, as were the factor VIII antigen, procoagulant, and the ristocetin cofactor activities. Platelet counts were obtained before and after exchanges and revealed significant decreases. Four hours after exchange, all parameters remained abnormal except the factor IX, ristocetin cofactor, and factor VIII procoagulant activities. By 24 hr, all hemostatic parameters had returned to normal. These studies indicate that plasma-exchange transfusion with material devoid of coagulation factors results in a coagulation defect that may be of clinical significance in a hemostatically compromised patient.

Amyotrophic Lateral Sclerosis↗
PubMed1978

Dysfibrinogenemia associated with hepatoma. Increased carbohydrate content of the fibrinogen molecule.

Abnormal coagulation studies indicative of a dysfibrinogen were found in the plasma of four of seven patients with malignant hepatoma. The abnormal fibrinogen was characterized by prolonged prothrombin, thrombin and reptilase times and inhibition of the coagulation of normal plasma. Purified fibrinogen revealed abnormalities similar to those in plasma. The functional defect was one of delayed polymerization of the fibrin monomer. The carbohydrate content of the abnormal fibrinogen was increased, and this change was related to the abnormal fibrinogen function. Enzymatic cleavage of sialic acid from the abnormal fibrinogen restored fibrinogen function to normal. This hepatoma-associated dysfibrinogen (acquired dysfibrinogenemia) is similar in many respects to fetal fibrinogen and may represent the presence of a fetal form of fibrinogen in hepatoma.

Blood Coagulation Disorders↗
PubMed1978

Osteosarcoma: improved survival with anticoagulation and amputation.

A study of warfarin anticoagulation as an adjunct to amputation of osteosarcomas was undertaken after finding dramatic results in experimental systems. Anticoagulation was started 7 days preoperatively, continued during the operation, and for up to six months postoperatively. Three of 21 (14%) non-anticoagulated control patients are alive at 5-11 years. Five of 9 (56%) of the anticoagulated patients remain alive 5-8 years. The presumed mechanism of increased survival is an inhibition of fibrin deposition around circulating tumor cells, thereby preventing their adherence to capillary endothelium to initiate metastasis formation.

Adolescent↗
PubMed1978

The 125I-fibrinogen euglobulin clot-lysis test.

A new method for determination of the rate of plasma fibrinolytic activity is presented. The method is based on the euglobulin clot-lysis test, modified by the addition in vitro of a small amount of normal I-labeled fibrinogen to the patient's eublobulin fraction. The rate of fibrinolysis is determined by the release of radioactivity from the clotted euglobulin fraction as a function of time. The rate is expressed as the fibrinolysis constant, which is the mathematical value for the fibrinolysis curve. Mean normal value for the fibrinolysis constant for 17 normal adult volunteers was 0.14 +/- 0.09 (2 SD). The major advantages of this technic are that it is not necessary to rely on complete dissolution of the clot for the end point, the majority of the euglobulin clot is the individual's own fibrin(ogen), and a quantitative and kinetic index of overall fibrinolytic activity can be obtained.

Blood Coagulation Tests↗
PubMed1978

Factor VIII/von Willebrand factor protein. Galactose a cryptic determinant of von Willebrand factor activity.

The normal Factor VIII/von Willebrand factor protein has the ability to agglutinate or aggregate normal platelets in the presence of ristocetin (von Willebrand factor activity). Removal of greater than 95% of the sialic acid from this protein by neuraminidase did not affect the von Willebrand factor or procoagulant activity. However, oxidation of the penultimate galactose of the asialo Factor VIII/von Willebrand factor protein with galactose oxidase resulted in a progressive loss of von Willebrand factor activity with no effect on procoagulant activity. Reduction of the 6-aldehydo intermediate by potassium borohydride caused full regeneration of von Willebrand factor activity. These studies confirm the identification of the intact penultimate galactose moiety as a critical determinant of von Willebrand factor activity.

Blood Coagulation Factors↗
PubMed1978

Plasma cofactors of platelet function: correlation with diabetic retinopathy and hemoglobins Ala-c.

We studied 29 diabetic patients (eight without and 21 with retinopathy) and 29 matched control subjects for hemoglobins Ala-c and plasma levels of fibrinogen, von Willebrand factor, and factor VIII/von Willebrand factor antigen. Hemoglobins Ala-c were elevated in all diabetic patients, regardless of retinopathy (P less than 0.001); fibrinogen was elevated only in those with retinopathy (P less than 0.001); and plasma von Willebrand factor was clearly elevated in those with proliferative retinopathy and minimally, if at all, elevated in those with background or no retinopathy. Plasma from five diabetic patients with proliferative retinopathy and five control subjects was tested for its ability to enhance the ADP-induced platelet aggregation of normal or von Willebrand platelet-rich plasma; no differences were found. We conclude that elevated levels of fibrinogen and von Willebrand factor, both recognized plasma cofactors of platelet function, are associated with proliferative diabetic retinopathy. A plasma factor that enhances ADP-induced platelet aggregation could not be found in diabetic plasma, and we doubt that increased von Willebrand factor is responsible for its finding by others.

Adenosine Diphosphate↗
PubMed1978

A model of fulminant hepatic failure in the rabbit.

A highly reproducible model of fulminant hepatic failure was developed by administering intravenously the selective hepatotoxin galactosamine hydrochloride (4.25 mmoles per kg) to genetically uniform rabbits. The great majority of rabbits died between 21 and 44 hr after injection following a period of coma which lasted 2.6 hr on average. Serum biochemical tests and liver histology reflected massive hepatic injury. Changes in plasma ammonia and amino acid concentrations, in coagulation parameters, and in the electroencephalogram were similar to those found in human fulminant hepatic failure. This model appears promising for future studies of the pathogenesis and treatment of fulminant hepatic failure.

Alkaline Phosphatase↗
PubMed1977

Von Willebrand's disease: combined qualitative and quantitative abnormalities.

Studies of von Willebrand's disease typically show either a quantitative or a qualitative abnormality of the factor VIII/von Willebrand factor protein. In studies of five patients we found a combination of quantitative and qualitative defects. Quantitative abnormalities included decreased levels of procoagulant, antigen and von Willebrand factor activities in the plasma and in the column fractions of cryopercipitate from gel chromatography. Qualitative abnormalities included annormal migration or shape of the crossed antigen-antibody arcs, disproportionate reduction of von Willebrand factor in relation to antigen, altered gel elution patterns of procoagulant, and von Willebrand factor activities the negative carbohydrate stain of the VIII protein on polyacryl-amide-gel electrophoresis and, in two patients, a decreased sialic acid content of factor VIII protein. Our studies indicate that von Willebrand's disease comprises both quantitative and qualitative defects.

Blood Coagulation Factors↗
PubMed1977

Multiple childhood osteosarcomas in an American Indian family with erythroid macrocytosis and skeletal anomalies.

Three of nine children of possibly consanguineous American Indian parents developed typical osteosarcoma in a 2-year period. Etiologic investigations detected limb anomalies and elevated mean corpuscular volumes (98--109 micrometer3) in the surviving tumor patient, several of her sibs, and her father. Limb anomalies included simple clinodactyly with brachymesophalangy, absence of one digital ray of the foot, and bilateral radioulnar synostosis. The red cell macrocytosis was not accompanied by anemia or explained by the usual causes. No unusual environmental exposures were found and screening for possible oncogenic viruses by culture, electron microscopy, and serology was negative. All family members had elevated antibody titers to Epstein-Barr viral antigens. The proband and her father had excessive chromosomal breaks in the bone marrow. This unusual familial pattern of osseous malignancy and malformation and defective erythropoiesis, tentatively called OSLAM syndrome, may represent impaired regulation of bone development.

Adolescent↗
PubMed1977

Blast crisis of chronic granulocytic leukemia. Morphologic variants and therapeutic implications.

Chronic granulocytic leukemia (CGL) terminates in a disease similar to acute leukemia. Except for a study indicating an increased response rate to the drugs, vincristine and prednisone, therapy of this terminal phase has been universally disappointing. We have studied the bone marrows and clinical courses of 67 patients in the terminal phase of CGL to discern if any parameters were associated with an increased response rate or survival. The results of this study indicate that patients who have a lymphoblastic morphology or hypodiploid cytogenetics in the terminal phase respond better to treatment with the combination of vincristine and prednisone than those with myeloblastic morphology or hyperdiploid cytogenetics. Response rate and survival are significantly increased in those with lymphoblastic morphology. Recognition of the heterogeneity of the terminal phase of CGL may dictate specific therapeutic modalities.

Adult↗