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Biomedical subjects

J S Wiley

Publications and source records attributed to J S Wiley.

At least 91 records · Page 5Linked to original sources
PubMed1982

Chronic lymphatic leukemia developing in a patient with multiple myeloma: immunologic demonstration of a clonally distinct second malignancy.

A patient with multiple myeloma who subsequently developed chronic lymphocytic leukemia is reported. Initial studies demonstrated clinical and hematological features of multiple myeloma with an IgM lambda paraprotein. Skeletal disease was a significant presenting feature, although relapse occurred in extraosseous sites, particularly the pleura. He developed chronic lymphatic leukemia 31 months later and immunological studies showed the malignant lymphocytes to have kappa (Kappa) light chain surface immunoglobulin, demonstrating separate clonal origin of this patient's two B-cell malignancies.

Aged↗
PubMed1982

Pruritus and severe iron deficiency in polycythaemia vera.

Six patients diagnosed as having polycythaemia vera had severe pruritus that persisted despite adequate haematological control. Iron supplementation was given when iron deficiency was noted in all six patients. The pruritus began to improve two to 10 days after the start of treatment and had completely disappeared after two to three weeks. In three patients the iron treatment was stopped because of unacceptably high haemoglobin concentrations; the pruritus recurred. Since chronic iron treatment may result in increases in red cell mass indiscriminate use of iron in patients with polycythaemia vera and pruritus is not advocated. Nevertheless, in patients with severe symptoms and evidence of iron deficiency treatment with iron, continuing for two to three weeks after the symptoms have abated, may be beneficial.

Aged↗
PubMed1982

Hereditary spherocytosis of man. Altered binding of cytoskeletal components to the erythrocyte membrane.

Human erythrocytes possess a lattice work of extrinsic proteins on the inner face of the membrane (;cytoskeleton') that maintains the shape and deformability of the cell. The major proteins of the cytoskeleton are spectrin and actin, which are attached to the membrane by protein bands 2.1 (;ankyrin') and 4.1. The interactions of spectrin/actin with erythrocyte membranes from normal subjects and from patients with hereditary spherocytosis (HS) have been studied by using an air-driven ultracentrifuge, which can rapidly separate membranes from soluble proteins (150000g for 30s). The total amount of spectrin/actin in HS and normal ghosts is similar. However, the rate of dissociation of spectrin and actin from HS erythrocyte membranes at low ionic strength is significantly lower than that observed for normal membranes. Spectrin and actin isolated from either HS or normal membranes re-associated in a similar manner to spectrin/actin-depleted vesicles prepared from normal cells. Scatchard analysis showed an average binding capacity of 278mug/mg of membrane protein. However, spectrin/actin-depleted vesicles prepared from HS cells bound significantly less spectrin/actin prepared from either the normal or abnormal cells (average binding capacity 158mug/mg of membrane protein). The defect was defined further by studying the cytoskeleton obtained by Triton X-100 extraction of membranes. Under conditions of low ionic strength cytoskeletons prepared from HS membranes dissociated more slowly than those prepared from normal membranes, and only 80% of the protein from HS cytoskeletons could be solubilized after 180min compared with 100% for normal cytoskeletons. The difference between HS and normal membranes, which persists in isolated cytoskeletons, suggests that alterations in either the primary structure or the degree of phosphorylation of protein bands 2.1 or 4.1 may be central to the molecular basis of hereditary spherocytosis.

Actins↗
PubMed1982

Calcium ions, drug action and the red cell membrane.

Intracellular calcium regulates a number of membrane functions in the erythrocyte, including control of shape, membrane lipid composition and cation permeability. Measurement of total red cell calcium has yielded values between 5 and 15 nmol/ml cells, and these low values in part reflect the absence of Ca2+ -containing organelles. Most intracellular Ca2+ is bound and the low cell ionized Ca2+ concentration (approximately 0.2 microM) is maintained by a combination of low membrane permeability and a powerful Ca2+ -pump. This pump has been identified with a (Ca2+ + Mg2+)-stimulated ATPase, and both Ca2+ transport and ATP splitting are stimulated by calmodulin, a low molecular weight protein which binds Ca2+ avidly and activates many Ca2+ -dependent enzymes. Both high and low affinity kinetics for Ca2+ pumping have been demonstrated, depending on the extent of binding of calmodulin to the pump. A stoichiometry of either 1 or 2 Ca2+ ions pumped per ATP molecule split has been shown, and the value may vary with the level of intracellular Ca2+. Phenothiazines, such as chlorpromazine inhibit the Ca2+ -pump by antagonizing the increment in activity produced by calmodulin. The passive inward leak of Ca2+ into erythrocytes can be quantitated by 45Ca2+ uptake into red cells whose Ca2+ -pump has been inhibited. Estimates of the Ca2+ permeability, based on unidirectional influx, yield values many orders of magnitude lower than for nucleated cells. Influx of Ca2+ into human erythrocytes occurs by a facilitated diffusion process, which can be inhibited by phenothiazines and the cinchona alkaloids. Calcium affects many membrane functions including cation permeability, lipid composition and some cytoskeletal interactions which may determine cell shape. Any rise in intracellular Ca2+ activates a specific K+ channel which normally makes little contribution to K+ fluxes. Kinetic studies of this process demonstrate either high or low affinity Ca2+ -activation of K+ efflux, with low affinity of the channel to Ca2+ being the probable state in vivo. Propranolol is the best known activator of Ca2+ -stimulated K+ efflux, although the mechanism of stimulation is unclear. Like other tissues, red cells possess a Ca2+ -activated phosphoinositol phosphodiesterase. Although it has been suggested that the echinocytic shape change induced by Ca2+ is due to the hydrolysis of polyphosphoinositides, it seems more likely that this shape change results from an effect of Ca2+ on the macromolecular interactions of the cytoskeleton. Abnormal Ca2+ permeability may contribute to red cell destruction in a variety of diseases. For example, in sickle cell anemia a large Ca2+ influx occurs when cells are sickled under deoxy conditions, and moreover, the ability of the Ca2+ -pump to extrude the increment of cell Ca2+ is impaired. Thus, red cell Ca2+ is increased 3-7-fold above normal and this may contribute to the short survival of sickle red cells...

Anemia, Hemolytic↗
PubMed1982

Cytosine arabinoside influx and nucleoside transport sites in acute leukemia.

Although cytosine arabinoside (araC) can induce a remission in a majority of patients presenting with acute myeloblastic leukemia (AML), a minority fail to respond and moreover the drug has less effect in acute lymphoblastic leukemia (ALL). The carrier-mediated influx of araC into purified blasts from patients with AML, ALL, and acute undifferentiated leukemia (AUL) has been compared to that of normal lymphocytes and polymorphs. Blasts showed a larger mediated influx of araC than mature cells, since mean influxes for myeloblasts and lymphoblasts were 6- and 2.3-fold greater than polymorphs and lymphocytes, respectively. Also, the mean influx for myeloblasts was fourfold greater than the mean for lymphoblasts. The number of nucleoside transport sites was estimated for each cell type by measuring the equilibrium binding of [(3)H]nitrobenzylthioinosine (NBMPR), which inhibits nucleoside fluxes by binding with high affinity to specific sites on the transport mechanism. The mean binding site numbers for myeloblasts and lymphoblasts were 5- and 2.8-fold greater, respectively, than for the mature cells of the same maturation series. The mean number of NBMPR binding sites for myeloblasts was fourfold greater than for lymphoblasts. Patients with AUL were heterogeneous since blasts from some gave values within the myeloblastic range and others within the lymphoblastic range. The araC influx correlated closely with the number of NBMPR binding sites measured in the same cells on the same day. Transport parameters were measured on blasts from 15 patients with AML or AUL who were then treated with standard induction therapy containing araC. Eight patients entered complete remission, while seven failed therapy, among whom were the three patients with the lowest araC influx (<0.4 pmol/10(7) cells per min) and NBMPR binding (<3,000 sites/cell) for the treated group. In summary, myeloblasts have both higher araC transport rates and more nucleoside transport sites than lymphoblasts and this factor may contribute to the greater sensitivity of AML to this drug. AraC transport varied >10-fold between leukemic blasts and normal leukocytes, but transport capacity related directly to the number of nucleoside transport sites on the cell. Finally, low araC transport rates or few NBMPR binding sites on blasts were observed in a subset of patients with acute leukemia who failed to achieve remission with drug combinations containing araC.

Acute Disease↗
PubMed1982

Increased calcium permeability of cold-stored erythrocytes.

The calcium, sodium, and magnesium permeability of erythrocytes from blood stored at 4 degrees C in various anticoagulant media has been studied and compared to that of fresh erythrocytes. Passive influx of CA2+ was measured at 37 degrees C in cells pretreated to abolish Ca2+ pumping and was up to fivefold greater for cold-stored erythrocytes than for fresh cells. The Ca2+ leakiness developed gradually after day 2 and reached a maximum by day 7 of cold storage in ACD, CPD, CPD-adenine, or heparin anticoagulants. The total calcium content of cold-stored erythrocytes in ACD was not significantly different from that of fresh erythrocytes. However, when cold-stored erythrocytes were reincubated at 37 degrees C in media containing 1.5 mM ionized calcium and substrates to regenerate ATP, a net gain of Ca2+ occurred that was greater for stored than for fresh erythrocytes. Cold storage of blood for up to 6 wk in any anticoagulant did not alter either sodium or magnesium permeability. Red cell ATP was also measured and fell steadily during cold storage in ACD or CPD, but more increase in Ca2+ permeability preceded any significant change in red cell ATP, it is likely that a selective calcium leak develops independently of the fall in ATP concentration that occurs on cold storage.

Adenosine Triphosphate↗
PubMed1981

Cation fluxes and volume regulation by human lymphocytes.

The ionic basis of volume regulation by human peripheral blood lymphocytes in hypotonic Tyrode's medium has been studied. The intracellular water space of lymphocytes increased to a maximum after 1 min in 0.68 X isotonic Tyrode's but returned to the isotonic value by 20 min at 37 degrees C. During this phase of volume regulation (1-20 min) both 42K+ efflux and 42K+ influx were stimulated severalfold, but the increase in 42K+ efflux exceeded the influx, resulting in a net loss of 20% of the lymphocyte K+. The increase in 42K+ efflux during the phase of cell shrinkage was unaffected by ouabain or by quinidine. Hypotonicity increased both the ouabain-sensitive (active) and ouabain-insensitive components of 42K+ influx by 76% and 123% respectively. Hypotonic shock stimulated 22Na+ influx by only 25%, but cell Na+ content was unchanged at 1 min and even decreased after 20 min. Thus active K+ influx and Na+ extrusion is increased by hypotonicity, but greater pumping cannot explain the net decrease in cell cations that leads to volume regulation. The 45Ca2+ uptake was not significantly changed by hypotonicity. Although volume regulation was abolished in a hypotonic high K medium, 42K+ efflux was still stimulated 2-fold by the reduction in tonicity. These findings support the hypothesis that volume regulation in hypotonic media occurs largely by a passive loss of cell K+, which results from a selective increase in membrane permeability to this ion. The increase in K+ permeability in hypotonic media is observed even in the absence of volume regulation by the cell.

Biological Transport↗
PubMed1981

Early nutritional depletion in critically ill children.

Nutritional status was evaluated in 50 medical admissions to a pediatric ICU. All patients were evaluated within 48 h of admission; none had chronic organ failure or malignancies. Nutritional assessment included weight/50th percentile weight for length, length/50th percentile length for age, triceps skinfold thickness, and midarm muscle circumference. Acute protein-energy malnutrition (PEM) occurred in 16% of all children. Chronic PEM also occurred in 16%. The nutrient stores of fat and somatic protein were deficient in 18 and 20% of all children. Acute PEM and deficient somatic protein stores were more frequent in children less than 2 years (p less than 0.05). These findings indicate that malnutrition and nutrient store deficiencies are common early in the course of critical illnesses in children, especially in those less than 2 years of age. However, the findings do not indicate if the severity of illness was the cause or effect of poor nutritional status.

Acute Disease↗
PubMed1981

Acanthocytosis and haemolytic anaemia due to the McLeod blood group.

A fourteen-year-old boy presenting with marked acanthocytosis of the red blood cells and a compensated haemolytic anaemia was shown to have the McLeod blood type. Only three other individuals have been reported as having this abnormality of the Kell blood group system without evidence of chronic granulomatous disease. Serological typing for the McLeod phenotype should be undertaken in males with unexplained acanthocytosis, and CPK estimation may provide a screening test for this condition.

Acanthocytes↗
PubMed1981

Increased erythrocyte cation permeability in thalassemia and conditions of marrow stress.

Calcium and sodium permeability of erythrocytes from patients with untransfused alpha- or beta- thalassemia major has been studied and compared to mature erythrocytes or control cells with comparable reticulocytosis. Isotopic Na(+) influx was increased a mean fourfold greater than normals and threefold greater than reticulocyte rich control. Passive net leak of Na(+) into thalassemic cells incubated with ouabain was also increased corresponding to their greater (22)Na(+) influx. Erythrocyte Na(+) and K(+) concentrations and cell water content per unit volume of cells were normal. Quantitation of active cation pumps in the cell membrane by the technique of [(3)H]ouabain binding showed a 2.6- to 9.9-fold increase above normal. Inward Ca(2+) movement was studied in cells with absent Ca(2+) pumping produced by depletion of either ATP or Mg(2+)-ions. Calcium uptake by ATP depleted thalassemic cells was increased 12-fold above normals and 3.6-fold above reticulocyte-rich controls. The Ca(2+) uptake by Mg(2+)-depleted thalassemic cells was also increased above normal confirming that erythrocyte Ca(2+) permeability is increased in this disease. Osmotic fragility measurements show that the surface area to volume ratio of thalassemic erythrocytes was increased by 15 to 25% above mature erythrocytes. The increased passive cation permeability of thalassemic erythrocytes cannot be explained by either reticulocytosis or an increased surface area to volume ratio of these cells. Moreover, erythrocyte Na(+) and Ca(2+) influxes in congenital dyserythropoietic anemia (CDA type 2) were increased 2- and 14-fold, respectively, above normal. The increased cation fluxes and cation pump numbers in thalassemic and congenital dyserythropoietic anemia erythrocytes are consistent with the hypothesis of membrane immaturity arising from rapid marrow transit times, a concept previously advanced to explain the persistence of i-antigen on these cells.

Adolescent↗
PubMed1979

Hereditary stomatocytosis: association of low 2,3-diphosphoglycerate with increased cation pumping by the red cell.

The levels of glycolytic intermediates have been measured in red cells from patients with both overhydrated and dehydrated varieties of the hereditary stomatocytosis syndrome. Red cell 2,3-diphosphoglycerate was reduced by 33% below normal in all patients with either stomatocyte or target cell morphologies (i.e. over or under hydrated varieties respectively). The relative decrement in 2,3-diphosphoglycerate was even greater when abnormal cells were compared with control cells with similar reticulocytosis. Red cell ADP concentrations in stomatocytosis were significantly increased above normal but ATP concentrations were not significantly changed. Whole blood oxygen affinity in stomatocytosis was increased in proportion to the lowered content of diphosphoglycerate. Some new parameters of membrane transport in hereditary stomatocytosis have been measured. Platelet K+ and Na+ concentrations and platelet K+ permeability were normal in stomatocytosis. The number of 3H-uridine transport sites in stomatocytes were increased by 9-39% above normal and this increment was the same as the increment in red cell lipids (0-38%). Hereditary stomatocytes contain 2-10-fold more cation pumps than normal and the increased active cation pumping may explain the high ADP, the low 2,3-diphosphoglycerate concentration and the increased oxygen affinity in this syndrome.

Adenosine Diphosphate↗
PubMed1979

The binding of ouabain to normal and chronic lymphocytic leukemic lymphocytes.

The binding of the cardiac glycoside, ouabain, to cells had been used to quantify the number of active cation pumps. In this study, lymphocytes were incubated with 3H-ouabain and the equilibrium binding analyzed for the maximal number of specific binding sites. Lymphocytes from normal peripheral blood bound 44,200 +/- 9920 molecules/cell, compared with 29,200 +/- 8370 molecules/cell for the lymphocytes of chronic lymphocytic leukemia (CLL) subjects. This difference was significant (p less than 0.01) and did not reflect a lower number of sites on B cells than T cells, since B-cell-enriched lymphocytes from normal peripheral blood showed the same ouabain binding characteristics as the standard T-cell-rich preparation. Although monocytes bind threefold more ouabain than lymphocytes, the small monocyte contamination (3.0%) in normal lymphocyte preparations could not account for the difference between normal and CLL. The fewer ouabain binding sites on CLL lymphocytes may reflect both their smaller size (by 10%) and lower mitotic activity compared with lymphocytes from normal peripheral blood.

B-Lymphocytes↗