Search PubMed⌕ Search

Biomedical subjects

J T Prchal

Publications and source records attributed to J T Prchal.

At least 109 records · Page 6Linked to original sources
PubMed1985

Hb Long Island: a hemoglobin variant with a methionyl extension at the NH2 terminus and a prolyl substitution for the normal histidyl residue 2 of the beta chain.

Hb Long Island was found in a diabetic man and his nondiabetic mother as the result of a routine clinical measurement of Hb AIc. It is present in amounts approximately equal to Hb A. Its alpha chains are normal but its beta chains have two alterations compared to the normal. A methionyl residue is attached to the usual NH2-terminal valyl residue. This valyl residue is followed by prolyl residue in place of the usual histidyl residue 2. The remaining sequence of the beta chain is normal. No hemoglobin or abnormal beta chain containing only the prolyl substitution could be detected by several different electrophoretic and HPLC procedures. We postulate that Hb Long Island is the result of a mutation in which a single nucleotide change causes the substitution of a prolyl residue for the normal histidyl residue at position 2 of the beta chain. We further postulate that this abnormal prolyl residue inhibits enzymatic cleavage of the initiator methionyl residue from the abnormal beta chain during posttranslational processing. Although the oxygen affinities of the whole blood, suspended cells, and hemolysate are normal, the affinity of the isolated Hb Long Island is slightly decreased and the effects of organic phosphates are reduced compared to normal. These changes are consistent with the loss of the normal histidyl residue 2 and the extension of the NH2-terminal end of the beta-chain molecule.

Adult↗
PubMed1985

An acute myeloproliferative disorder characterized by myelofibrosis and blast cells that express phenotypic properties associated with multiple hematopoietic lineages.

The authors investigated the blast cells obtained from two patients with acute myelofibrosis with the use of recently developed immunochemical and ultrastructural markers. They intended to examine the expression of megakaryoblastic, erythroblastic, myeloblastic, and monoblastic properties in these cells. Respectively, 20% and 15% of the blasts from patient 1 and patient 2 expressed a megakaryoblastic phenotype as determined by reactivity with a polyclonal platelet glycoprotein antisera (PGP). However, 55% and 73% of these patients' blasts also exhibited myeloid/monocytic properties. Ultrastructural studies clearly demonstrated findings consistent with the presence of myeloblasts, monoblasts, and erythroblasts, as well as undifferentiated agranular blasts. These findings demonstrate the existence of a disorder in which blast cells simultaneously express properties associated with multiple hematopoietic lineages. This disorder is characterized by impaired terminal differentiation.

Acute Disease↗
PubMed1985

Plasmacytoid T-cell lymphoma associated with chronic myeloproliferative disorder.

This study reports the case of a patient who presented with evidence for a diagnosis of chronic myelogenous leukemia, as shown by blood and bone marrow analysis, and with generalized lymphadenopathy and splenomegaly. A lymph node biopsy revealed that the majority of the cells had plasmacytoid features but were consistently negative for surface or cytoplasmic immunoglobulin products, myelomonocytic surface markers, and peroxidase. Rather, lymph node plasmacytoid cells expressed T-cell markers (T 4/Leu 3+, T 10+), transferrin receptors (T 9+), and a proportion of them was also positive for sheep erythrocyte receptors (T 11/Leu 5+). This case is strikingly similar to a case reported by Lennert's group with respect to morphology, surface phenotypic features of the malignant plasmacytoid cells, and the association between a lymphoproliferative and a myeloproliferative disorder. This association suggests that plasmacytoid T-cells might exert a regulatory role on proliferation of myeloid cells.

Aged↗
PubMed1985

Expression of NK-lineage markers on peripheral blood lymphocytes with T-helper (Leu3+/T4+) phenotype in B cell chronic lymphocytic leukemia.

Heterogeneity within lymphocyte subsets expressing T-helper (T4+/Leu3+) or T-suppressor (T8+/Leu2+) markers was analyzed in 38 patients with B cell chronic lymphocytic leukemia (B-CLL) and in 11 age-matched controls. Co-expression of NK-lineage markers (M1, Leu7) on Leu2+ or Leu3+ cells was investigated by two-color immunofluorescence, and the proportion of granular lymphocytes within each subset was determined by cytochemical staining for acid phosphatase. B-CLL patients and normal controls had similar absolute numbers of cells per microL with T-suppressor phenotype. However, the proportion of Leu2+ cells co-expressing the Leu7 antigen was higher in the B-CLL patients than in the control subjects (54 +/- 3% v 27 +/- 4%, P less than .0001). The absolute number per microL of cells with T-helper phenotype was somewhat decreased in B-CLL patients compared with normal subjects (649 +/- 104 v 799 +/- 33, P less than .02), with a consequent decrease of the helper/suppressor ratio. Furthermore, co-expression of the Leu7 and, more strikingly, of the M1 markers was increased significantly on Leu3+ cells from B-CLL patients compared with normal controls (11 +/- 2% v 2 +/- 0.7%, P less than .002 for Leu7 and 40 +/- 5% v 4 +/- 1%, P less than .00001 for M1). Cytochemical studies showed that a large proportion of Leu3+ cells from B-CLL patients were granular lymphocytes, as suggested by the co-expression of natural killer (NK) cell markers. The emergence of a population of Leu3+ granular lymphocytes with NK markers, which is barely detectable in normal subjects, may provide an explanation for the impairment of T cell functions repeatedly described in B-CLL.

Adult↗
PubMed1985

Autosomal dominant polycythemia.

Two families with polycythemia inherited as an autosomal dominant trait are described. Serial hemoglobin determinations in multiple family members and RBC volume measurements in selected affected subjects documented their polycythemia. Measurements of arterial p02s, p50s, and blood oxygen affinity were normal in all affected individuals from each family who were tested. Erythropoietin (EPO) levels were low in affected individuals from family 1 and normal in affected members of family 2. Stimulation of in vitro CFU-E colony growth by low levels of EPO was significantly increased in subjects from family 1, but normal in those affected from family 2. We conclude that although the inheritance pattern for the polycythemia in both of these families appeared to be the same, the biologic defect leading to the disorder in each of these unique families was different. The precise mechanism of the increased EPO sensitivity noted in affected subjects from family 1 awaits elucidation.

Adenosine Triphosphate↗
PubMed1984

Blastic transformation of essential thrombocythemia: dual expression of myelomonoblastic/megakaryoblastic phenotypes.

Three patients developed blastic transformation of essential thrombocythemia (tET). Morphological studies in all patients showed that the majority of blasts had either myeloblastic or myelomonoblastic differentiation. Immunologic assays of hematopoietic cells were performed in two patients. In patient 1, 86% of peripheral blood mononuclear cells (predominantly blasts) reacted with a monoclonal antibody specific for granulocytes and monocytes (MMA), and 15% of mononuclear cells reacted with Tab, a monoclonal antibody specific for megakaryocyte-platelet glycoproteins (PGP) IIb and IIIa. In patient 2, 41.5% of peripheral blood mononuclear cells (predominantly blasts) were MMA-positive, 22.5% were Tab-positive, and 40% reacted with rabbit anti-human PGP. These results suggest either that two subpopulations of blast cells exist in tET, or that blast cells simultaneously express surface markers of myeloblastic/monoblastic and megakaryoblastic differentiation. In these three and in nine previously reported cases of tET, neither age, sex, nor previous therapy were obvious etiologic factors. tET occurred 24.2 +/- 14.4 mo after diagnosis of essential thrombocythemia, and a majority of patients had hepatomegaly and/or splenomegaly, anemia, leukocytosis, and thrombocytopenia. Leukemic cell morphology was myeloblastic and/or monoblastic in 12/12 patients, 5/12 had marrow fibrosis. Despite various treatments, death occurred in 3.6 +/- 2.7 mo; one patient had a brief complete remission.

Aged↗
PubMed1984

Gas chromatographic analysis of lens monosaccharides.

Gas-liquid chromatography was employed to determine free monosaccharides in human, rat, and South American rodent Octodon degu lenses. In addition to D-glucose, D-fructose, sorbitol and myo-inositol, which were previously known to be components of lens tissue, glycerol, erythritol, threitol, ribitol, xylitol, and mannitol were also detected in the lenses of these three species. The concentrations in lenses of these three species were in the following ranges: glycerol 1.2 to 40 mumol/gm wet tissue; myo-inositol 4 to 25; and glucose, fructose, and remaining alditols 0.01 to 1.4/mumol/gm. The method is described and its applicability to analyses of free monosaccharides in other animal tissues is discussed.

Animals↗
PubMed1983

Successful treatment of thrombotic thrombocytopenia purpura by vincristine.

Two patients with thrombotic thrombocytopenia purpura (TTP) are described in whom vincristine administration appeared to play a role in successful outcomes. The first patient with chronic TTP responded partially to plasma exchange followed by plasma infusion and transiently to splenectomy, but developed a complete long lasting remission after a single injection of intravenous vincristine. The second patient developed a complete remission following vincristine administration and plasma exchange. Although vincristine's mechanism of action in TTP is obscure, we suggest that vincristine is effective in the treatment of this infrequent and often fatal disease.

Adult↗
PubMed1983

Abnormal T-cell functions in B-cell chronic lymphocytic leukemia do not imply T-lymphocyte involvement in the leukemic process: report of a case with demonstrated "polyclonality" of T lymphocytes.

In a patient with chronic lymphocytic leukemia (CLL), we previously demonstrated by glucose-6-phosphate isoenzyme analysis that monoclonality was restricted to B lymphocytes. Isolated T cells expressed both isoenzymes and, therefore, were apparently not involved in the leukemic process. This report presents results of a functional analysis of the patient's T cells. Cutaneous anergy to a battery of skin tests was correlated with abnormal proliferative responses of isolated T cells to phytohemagglutinin and concanavalin A. The addition of sufficient numbers of autologous adherent cells restored mitogen responses to nearly normal levels. However, the patient's T cells failed to provide help for differentiation of allogeneic B cells in response to pokeweed mitogen. These data suggest that altered cellular immunity in CLL is not necessarily due to intrinsic T cell abnormalities. Reduced numbers of circulating accessory cells and/or an imbalance in T-cell subsets related to the expansion of the leukemic B-cell clone may play a significant role.

B-Lymphocytes↗
PubMed1983

Hemolytic anemia, recurrent metabolic acidosis, and incomplete albinism associated with glutathione synthetase deficiency.

The clinical and laboratory features of a 3-mo-old black male infant with glutathione (GSH) synthetase deficiency of the generalized type was evaluated. Partial albinism, brisk hemolytic anemia, recurrent febrile episodes, and mental retardation were noted. Also, severe recurrent metabolic acidosis and marked oxoprolinemia and oxoprolinuria were found in the proband but not in his first-degree relatives. The relationship of these disease manifestations to the underlying metabolic defect is discussed.

Acidosis↗
PubMed1982

Studies of nicotinamide adenine dinucleotide methemoglobin reductase activity in a Jewish population.

In the original study of the deleterious effects of oxidant drugs on persons heterozygous for nicotinamide adenine dinucleotide reductase (NADH MetHb R) deficiency, several Jewish physicians used as controls had decreased enzyme activity. We collected blood samples from 555 Jewish persons to 1) estimate the heterozygote frequency for NADH MetHb R deficiency; and 2) determine if external variables such as age, gender, and ingested medications may alter the NADH MetHb R activity and thereby alter estimates of heterozygosity. Two persons possibly heterozygous for the deficiency were identified (carrier incidence = 1/309,000 jewish births). A difference in enzyme activity was found between males and females (P less than 0.03). We have examined the influence of the mean red cell age on the activity of erythrocyte NADH MetHb R and found it not to be materially influenced by mean red cell age; thus the possible intersex differences of mean red cell age cannot explain this observation. No significant difference (P greater than 0.1) was seen between persons ingesting the following drugs and those not: Dilantin; antidepressants/sedatives; cardiac, antineoplastic, or antigout/antiinflammatory drugs; thyroid supplements, estrogen-containing preparations, and antihistamines. NADH MetHb R activity did not correlate with age or spontaneous abortion. We conclude that heterozygosity for NADH MetHb R deficiency is not prevalent among Ashkenazic Jewish persons, and that external variables should be considered to ensure accurate interpretation of NADH MetHb R activity for correct estimation of heterozygosity.

Adolescent↗
PubMed1982

Defective spectrin dimer-dimer association with hereditary elliptocytosis.

We examined erythrocytes from 18 patients with hereditary elliptocytosis. Spectrin from eight patients (referred to as type 1) was defective in dimer-dimer association as demonstrated in two ways. First, there was an increased amount of spectrin dimer with a concomitant decrease in tetramer as measured in erythrocyte membrane preparations extracted at 0 degrees C under low-salt conditions (the amount of spectrin dimer was 15-33% of total spectrin species compared with a normal range of 3-7%). Second, the equilibrium constants of spectrin dimer-dimer association were decreased in both solution and in situ membrane. Spectrin from the remaining 10 patients (referred to as type 2) showed normal dimer-dimer association. Membrane skeletons, produced from ghosts of both types of hereditary elliptocytosis by Triton X-100 extraction, were unstable when mechanically shaken. Because spectrin tetramers, but not dimers, can crosslink actin, we postulate that the defective spectrin dimer-dimer association in type 1 diminishes actin crosslinking and thus is responsible for membrane skeletal instability. A defective protein-protein association in type 2, however, remains to be identified.

Elliptocytosis, Hereditary↗
PubMed1982

Hereditary pyropoikilocytosis and elliptocytosis: clinical, laboratory, and ultrastructural features in infants and children.

Clinical, biochemical and ultrastructural assessment of five Black children from four unrelated kindreds, who had morphologic and laboratory features of hereditary pyropoikilocytosis (HP) is described. In two of the unrelated propositi, both with relatives having elliptocytosis, the apparent HP gradually evolved into elliptocytosis. The mode of inheritance appeared to be autosomal dominant in one family and autosomal recessive in the other. None of the three children from two separate families with true HP had a parent with HP or elliptocytosis. A sixth Black child, whose mother also had elliptocytosis, demonstrated typical elliptocytosis from birth and never demonstrated the HP phenotype. Sequential quantitation of heat induced red cell fragmentation using histogram analyses revealed unchanged findings in three patients with true HP but progressive amelioration in the two patients with HP phenotype who eventually developed elliptocytic morphology. Previously unreported lesions in both true and apparent HP patients included endovesicle formation and submembrane particles, which were detected by electron microscopy, an increase in Heinz body formation, and elevation of oxidized glutathione levels. Our study demonstrates shared abnormalities present both in some neonates with elliptocytosis and in neonates with HP, which preclude the diagnosis of HP in infancy and provide further evidence of the heterogeneity of the elliptocytosis syndrome.

Anemia, Hemolytic, Congenital↗
PubMed1982

Linkage studies in carriers of Lowe oculo-cerebro-renal syndrome.

A black family with two male infants affected with the X-linked Lowe syndrome was studied. All three females in the pedigree were found to be carriers on the basis of lenticular opacities. Each female had one son. Of these, two were affected and one was unaffected. The Xg blood-group locus and the G6PD locus were determined in these six individuals. Two of the carrier females were heterozygous for G6PD isoenzymes A- and B. Skewing of the A-:B ratio in isolated erythrocytes, lymphocytes, granulocytes, platelets, and cultured skin fibroblasts from these females may be the result of either selection against cells expressing the Lowe gene product or random X-chromosome inactivation. At least one instance of recombination was found between the G6PD and the Lowe syndrome loci. At least two instances of recombination between Xg blood-group and Lowe syndrome loci.

Adolescent↗
PubMed1981

Immunoblastic lymphoma: an immunologic study.

An immunologic study of a 59-year-old man with immunoblastic lymphoma is presented. Shortly after his hospital admission, an uncompensated hemolytic process developed, caused by cold agglutinins. These antibodies had anti-i specificity, were of low titer at cold temperature, but demonstrated a high thermal amplitude. An apparent paraprotein was found by further immunochemical analysis to be polyclonal. The majority of cells in the peripheral blood (over 2000/cu nm), lymph node, and bone marrow that contained cytoplasmic IgG or IgM were plasma cells, although a small number of cells resembled lymphoblasts. Their staining with anti-lambda and anti-kappa chain reagents confirmed the polyclonality of the immunoglobins. Some plasma cells displayed the concomitant presence of both IgM and IgG immunoglobulins. Free immunoglobin was also demonstrated intercellularly in the lymph node section. The patient's acute hemolysis was controlled by plasmapheresis and eventually by combination chemotherapy. After chemotherapy, the clinical improvement was rapid, immunoglobulin levels returned to normal, and the patient remains asymptomatic 40 months after completing six courses of combination chemotherapy. This report provides evidence for polyclonal proliferation of B-lymphocytes in immunoblastic lymphoma.

Agglutinins↗
PubMed1981

Extramedullary blast transformation in the central nervous system in idiopathic myelofibrosis.

Idiopathic myelofibrosis (IM) is a myeloproliferative syndrome characterized by anemia, fibrosis of the bone marrow, variable proliferation of megakaryocytes, myelocytic and erythrocytic precursors, and splenomegaly. Extramedullary hematopoiesis can develop in diverse areas. Unlike in chronic granulocytic leukemia, transformation to acute leukemia is uncommon in IM. Transformation to acute leukemia is usually accompanied by the findings of progressive increase in blasts in peripheral blood or bone marrow [1]. We have recently treated a patient with an unusual transition from IM to acute leukemia in whom leukemic transformation began in the central nervous system.

Central Nervous System Diseases↗