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Biomedical subjects

W Krivit

Publications and source records attributed to W Krivit.

At least 181 records · Page 10Linked to original sources
PubMed1976

Acute and chronic effects of methotrexate on hepatic, pulmonary, and skeletal systems.

With the progressive improvement in the survival of children with acute lymphocytic leukemia, the question of late effects of therapy on normal tissue becomes a more significant problem. In a review of a large number of children who have received long-term treatment with chemotherapy, especially methotrexate, a significant increase in the serious effects on hepatic, pulmonary, and skeletal tissue was noted. A review of the methotrexate-induced acute and chronic changes seen in these tissues is the basis for this report.

Bone and Bones↗
PubMed1976

Prognostic significance of surface marker analysis in childhood non-Hodgkin's lymphoproliferative malifnancies.

Blast cell surface markers for T- and B-lymphocyte characteristics were studied at diagnosis in 73 children with non-Hodgkin's lymphoproliferative malignancies. Three distinctive groups of patients were identified on the basis of the analysis of blast cells for surface immunoglobulin (SIg), sheep erythrocyte (sE) rosette formation, and complement receptors, The seven group I patients had monoclonal IgM on their blast cells, morphologic features of Burkitt's lymphoma, abdominal masses, and very short survival. The 13 group II patients had receptors for sE, complement, or both on their blast cells, mediastinal or nodal masses, and short survival. The distinction between leukemia and lymphoma based on the presence of bone marrow involvement at diagnosis is not prognostically useful in this group of patients. The blast cells of group II patients could not be morphologically distinguished from those of the group III patients. The 53 groups III patients had SIG, sE, and complement negative blast cells and could be further subdivided on the basis of while blood cell count. The nine group IIIA patients (greater than 100.0 X 10(9)/liter) had in general short survival, while most of the 44 group IIIB patients (less than than 100.0 X 10(9)/liter) have remained in complete remission. Positive surface markers, mass lesions, male sex, and age of diagnosis less than 2 years of greater than or equal to 10 years appear to be interrelated factors indicating poor prognosis. Elevated while blood cell count is a prognostic indicator independent of surface marker analysis or presence of mass lesions.

Adolescent↗
PubMed1976

Complex alpha-thalassemia-like syndrome: a cause of neonatal normoblastemia.

A previously unrecognized hypochromic anemia associated with marked normoblastemia during the newborn period is reported. One male and two female siblings and a first cousin had a hypochromic anemia and marked normoblastemia (300 to 900 normoblast index per 100 white blood cells) at birth. Globin chain synthesis studies on peripheral blood of the proband at birth indicated the presence of alpha-thalassemia trait with possible reduced gamma chain synthesis. Studies of globin chain synthesis on the father, two older affected siblings of the proband, and the proband at 1.5 years of age revealed alpha-thalassemia trait. The data suggest this complex alpha-thalassemia-like condition as a new syndrome associated with marked neonatal normoblastemia.

Adolescent↗
PubMed1976

A hypothesis for the increased oxygen affinity in haemoglobin Malmö.

Haemoglobin Malmöbeta97His leads to Gln, a high oxygen affinity haemoglobin which causes secondary erythrocytosis, is transmitted in an autosomal dominant manner. A hypothesis accounting for the high oxygen affinity, hyperbolic oxyhaemoglobin dissociation curve, and the relatively normal Bohr effect is presented. The purified abnormal haemoglobin from the present family provided biochemical and functional data for this hypothesis based on the allosteric model proposed by Perutz. Experimental results support the formation of a chemical bond between the -SH proton of the beta93 cysteine and the amide of oxygen of the substituted beta97 glutamine as an explanation for the high oxygen affinity of haemoglobin Malmö.

Hemoglobinopathies↗
PubMed1976

Labile aggregation stimulating substance, free fatty acids, and platelet aggregation.

Labile aggregation stimulating substance (LASS), an intermediate produced during platelet biosynthesis of PGE2 and PGF2alpha, acts as a physiologic intercellular messenger to promote platelet aggregation and the release reaction. The activity is formed by intact cells after physiologic stimulation or can be generated from platelet membrane fractions after combination with arachidonate. In the present investigation, small amounts of polyunsaturated fatty acids added to an incubation mixture of platelet microsomes and arachidonate were found to significantly inhibit subsequent platelet aggregation. Saturated and mono-unsaturated fatty acids in the same concentrations were without effect. However, in higher concentrations mono-unsaturated fatty acids were found to be inhibitory and stearic acid was found to enhance subsequent platelet aggregation. The inhibition caused by the polyunsaturated fatty acid, linoleate, was shown to be the result of an effect on the production of LASS through an interaction with the platelet enzyme responsible for conversion of arachidonate to LASS. In contrast, stearic acid was found to enhance platelet aggregation by acting on the platelets and not directly on LASS production. The results suggest that small changes in the fatty acid composition of platelet phospholipids could significantly influence platelet reactivity.

Arachidonic Acids↗
PubMed1975

Metabolism of neutral glycosphingolipids in plasma of a normal human and a patient with Fabry's disease.

[6-2H2]Glucose was used as a tracer for a comparative study on the metabolism of the neutral glycosylceramides in plasma of a control subject and a patient with Fabry's disease. The incorporation of the tracer into the glucosyl and galactosyl moieties of the glycosphingolipids was measured by gas chromatography-mass spectrometry of the tetra-0-acetyl methyl glycoside derivatives. Experiments on the precision and accuracy for measurements of [6,6-2H2]hexose in a sample demonstrated that incorporation of 0.2% or more of [6,6-2H2]glucose could be detected with a 95% confidence limit of +/-0.16%. The labeled substrate (35g) was infused into each subject with a 5-g priming dose and the remainder administered at a constant rate of 3 g/hour over a 10-hour period. During the infusion, the plasma glucose of each subject attained a concentration of about 30% [6,6-2H2]glucose which diminished rapidly after the administration of substrate was complete. A concentration of 0.8% [6,6-2H2]glucose was observed in glucosylceramide (GL-la) from plasma of both subjects between 48 and 72 hours after the infusion began. The label disappeared from this lipid at a logarithmic rate and 0.2% or less of the molecules were labeled 9 days after the experiment began. In contrast to the results with GL-la, the maximum incorporation of [6,6-2H2]hexose into lactosylceramide (galactosyl-(beta1 leads to 4)-glucosylceramide) was 2-fold higher in the Fabry patient (1.6%) than in the control (0.8%). The trihexosylceramide (galactosyl-(alpha1 leads to 4)-galactosyl-(beta1 leads to 4)-glucosylceramide, GL-3a) from plasma of the control reached a maximum of 0.4% [6,6-2H2]hexose in both the glucosyl and galactosyl moieties whereas the GL-3a from the Fabry patient was not significantly labeled. The maximal labeling of the GL-4a fraction (N-acetyl-galactosaminyl-galactosyl-galactosyl-glucosylceramide) was slightly depressed in the Fabry patient (0.4%) as compared to the control (0.7%). Turnover times for the glycosphingolipids of plasma were calculated to be from 4 to 8 days and the turnover rates were from 1 to 6 mumol/day.

Adult↗
PubMed1975

Lymphocyte transformation in leukemic serum.

Cultures of normal lymphocytes were induced to transform by pokeweed mitogen (PWM). Inhibition of transformation was observed when these cultures contained sera isolated from children with acute lymphoblastic leukemia (ALL). The inhibition of transformation of normal lymphocytes was best demonstrated when the concentration of the leukemic serum in the culture medium was relatively high (60 percent); however, the inhibition was also observed with a more standard serum concentration (20 percent). Not all leukemic sera were inhibitory. Pretreatment sera from newly diagnosed patients with leukocyte counts greater than 50,000/mm3 were significantly inhibitory. Pretreatment sera from newly diagnosed patients with leukocyte counts less than 50,000/mm3, and sera from patients in remission or relapse had no significant effect. The inhibition observed with the sera of the high leukocyte count group was not believed to be related to cytotoxicity. The significance of this inhibitor in relation to clinical prognosis needs to be investigated.

Child↗
PubMed1975

Bis-(N-maleimidomethyl) ether: an antisickling reagent.

The interaction of bis-(N-maleimidomethyl) ether with oxyhemoglobin results in covalent linkages of both maleimide groups, converting them to succinyl derivatives of beta93 Cys and beta97 His at their sulfhydryl and imidazolyl side chains, respectively. The resultant hemoglobin is stable, and reveals a left-shifted oxyhemoglobin equilibrium curve in which cooperativity is abolished. This reagent readily traverses the red cell membrane and prevents the sickling reaction upon deoxygenation. It appears to affect none of the activities of the red cell enzymes adversely, nor does it appear to affect the red cell membrane. Since there are several defined effects on the stereochemical status of the molecule conferred by interaction with bis-(N-maleimidomethyl) ether, the precise mechanism of the anitsickling effect remains to be elucidated. A more subtle perturberant will be required to specify a precise antisickling effect. By use of bis-(N-maleimidomethyl) ether a precise locus on the beta chain of human hemoglobin S can be perturbed to produce the desired effect.

Anemia, Sickle Cell↗
PubMed1975

Oncornavirus-like particles from cultured bone marrow cells preceding leukemia and malignant histiocytosis.

Particles with the density and enzymatic activity characteristic of known oncornavirus have been previously described in bone marrow cells from patients with leukemia in relapse and in remission. We have confirmed these findings and studied two patients in whom preleukemia was among the diagnostic considerations. Following cultivation of bone marrow from these patients for 1 week in conditioned media with dexamethasone, a high-speed pellet of the supernatant fluid and disrupted cells was prepared and analyzed on a sucrose gradient for enzymatic activity characteristic of RNA-directed DNA polymerase (reverse transcriptase). Peaks of endogenous DNA polymerase activity showing ribonuclease sensitivity and/or stimulation with the synthetic template poly(rC)-(dG)12-18 were demonstrated in both patients at densities of 1.15 to 1.19 and 1.21 to 1.24 g/ml. Subsequently, diagnosis 2 and 4 months after initial evaluation revealed acute myelogenous leukemia and malignant histiocytosis, respectively. Prior studies have suggested a possible etiological significance of such particles in human leukemia. The demonstration of similar particles preceding clinically overt disease in these patients supports this hypothesis and offers the possibility of early diagnosis and treatment.

Adolescent↗
PubMed1975

Retransplantation of human bone marrow. Two immunosuppressive drug regimens.

A 15-year-old boy with aplastic anemia was successfully retransplanted with matched sibling bone marrow after failure of a first transplant from the same donor. Cyclophosphamide was used as immunosuppression for the first transplant, and cyclophosphamide plus procarbazine plus antithymocyte globulin were used for the second transplant. Laboratory studies of peripheral blood and bone marrow karyotypes and T and B lymphocytes supported the conclusion that immunosuppression was inadequate for the first transplant, but adequate for the second transplant.

Adolescent↗
PubMed1975

Labile aggregation stimulating substance (LASS): the factor from storage pool deficient platelets correcting defective aggregation and release of aspirin treated normal platelets.

Mixtures of equal volumes of Hermansky-Pudlak (HP) syndrome (adenine nucleotide storage pool deficient) and aspirin treated (AT) platelets (inhibited release of adenine nucleotides) undergo irreversible aggregation when exposed to collagen or adrenaline, whereas neither alone will do so. The present investigation has explored the basis for the mutual correction. Correction in the mixed system was accompanied by release of significant amounts of [14C]5-hydroxy-tryptamine from the AT platelets, whereas very little isotope was released when AT platelets alone were exposed to collagen. The correction of aggregation and the release of isotope could both be suppressed by pre-treating HP platelets with aspirin. Labile aggregation stimulating substance (LASS) composed of two closely linked intermediates of prostaglandin (PG) E2 and PGF2alpha biosynthesis, produced using a microsomal fraction of HP platelets, could correct the aggregation and secretion defect of AT platelets exposed to collagen. These findings indicate that HP platelets when mixed with AT platelets and exposed to collagen secrete a substance which is responsible for the correction. LASS, identified as the factor involved, acted as an intercellular messenger which mediated the correction by overcoming the influence of aspirin on normal cells.

Adenine Nucleotides↗