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Biomedical subjects

W C Mentzer

Publications and source records attributed to W C Mentzer.

At least 73 records · Page 4Linked to original sources
PubMed1982

Inhibitors of sickling.

A number of agents that prevent sickling in vitro have been discovered during the past decade. In general, such agents act directly on the hemoglobin S tetramer to inhibit gelation or alter oxygen affinity. Most currently recognized agents lack specificity for hemoglobin and modify other cellular constituents. Synthesis of reagents such as the bifunctional aspirin derivative, bis (3,5-dibromosalicyl) fumarate, with increased specificity for hemoglobin, represents a rational approach to the design of new therapeutic agents for sickle cell anemia. Membrane active agents such as cetiedil inhibit sickling in vitro but have not yet been shown to be effective in vivo. Reduction in the intracellular concentration of hemoglobin S apparently may reduce the frequency of painful crises but is difficult to achieve with current techniques. Although no antisickling therapy can yet be described as both safe and effective, the outlook for the future seems promising because of the large number of agents under active investigation.

Antisickling Agents↗
PubMed1981

Evaluation of the opsonic requirements for phagocytosis of Streptococcus pneumoniae serotypes VII, XIV, and XIX by chemiluminescence assay.

A luminol-enhanced chemiluminescence assay was used to investigate opsonic requirements for phagocytosis of STreptococcus pneumoniae serotypes VII, XIV, and XIX. After opsonization with whole immune sera (with antibody and total complement pathway), heat-inactivated immune sera (with antibody alone), or magnesium dichloride-ethylene glycol tetraacetic acid-chelated immune sera (with antibody and alternative complement pathway), live S. pneumoniae cells were incubated at 37 degrees C with normal polymorphonuclear leukocytes while serial chemiluminescence measurements were recorded. The amount of chemiluminescence observed correlated closely with evidence of phagocytosis as observed by microscopy. Complement was required for efficient opsonization, since all three serotypes showed a slower rise and less integral chemiluminescence after opsonization with heat-inactivated serum as compared with whole serum. The alternative pathway provided opsonic activity equal to that of the total complement pathway for type XIX, but only intermediate activity for types VII and XIV. Type-specific antibody was also required for effective opsonization of all three serotypes since chemiluminescence was markedly reduced when bacteria were opsonized with antibody-depleted serum (serum absorbed with type-specific S. pneumoniae cells at 4 degrees C). Thus, chemiluminescence proved to be an effective means of defining the requirement for both antibody and complement in the opsonization and phagocytosis of S. pneumoniae.

Adult↗
PubMed1980

G6PD San Francisco: a new variant of glucose-6-phosphate dehydrogenase associated with congenital nonspherocytic hemolytic anemia.

Congenital nonspherocytic hemolytic anemia in an adult male of Scandinavian ancestry was associated with virtual absence of G6PD activity in red cells. Characterization of G6PD purified from leukocytes using standard WHO techniques revealed diminished electrophoretic mobility, marked lability on heating at 46 degrees C, normal pH optimum and utilization of alternate substrates (2-deoxy G6P, D-amino NADP), elevated Km NADP, and striking susceptibility to NADPH inhibition. The variant G6PD, which appears to be unique, has been designated G6PD San Francisco. An unusual feature of the variant enzyme, susceptibility to inactivation by brief periods of dialysis, could be prevented by addition of 200 microM NADP to the dialysis solution. In red cells, where G6PD activity was essentially absent, regeneration of reduced glutathione was totally curtailed in vitro, while in leukocytes, where residual G6PD activity was approximately 60% of normal, hexose monophosphate shunt activity, oxygen consumption during phagocytosis, and bacterial killing were unimpaired. Thus, instability of the variant enzyme rather than its unfavorable kinetics appeared to be an important determinant of abnormal cell function.

Adult↗
PubMed1979

Modification of hemoglobin H disease by sickle trait.

The rarity of hemoglobin (Hb) H disease in combination with sickle trait may be due in part to the absence of actual Hb H in individuals who, nonetheless, have inherited the deletion of three alpha-globin genes. We describe here a boy with persistent microcytic, hypochromic anemia despite adequate iron stores, who exhibited splenomegaly with a normal reticulocyte count and only rare inclusions in circulating erythrocytes. Starch gel electrophoresis and isoelectric focusing at age 5 yr showed 21% Hb S, persistent Hb Bart's, but no Hb H. Recticulocyte alpha/non-alpha globin chain synthesis ratio was 0.58 at age 5. The mother (Asian) had laboratory evidence of alpha-thalassemia trait and the father (Black) had sickle trait. The nature of alpha-thalassemia in this patient was investigated both by liquid hybridization and by the Southern method of gene mapping, in which DNA is digested with restriction endonucleases and the DNA fragments that contained the alpha-globin structural gene identified by hybridization with complementary DNA. The patient had only one alpha-globin structural gene, located in a DNA fragment shorter than that found in normal or alpha-thalassemia trait individuals, but similar to that present in other patients with Hb H disease. Morphologic studies of bone marrow by light and electron microscopy revealed erythroid hyperplasia with inclusions in polychromatic and orthochromatic erythroblasts, suggesting early precipitation of an unstable hemoglobin. The lack of demonstrable Hb H may be the result of both diminished amounts of beta(A) available for Hb H formation (since one beta-globin gene is beta(S)) and the greater affinity of alpha-chains for beta(A) than beta(S)-globin chains leading to the formation of relatively more Hb A than Hb S. The presence of a beta(S) gene may thus modify the usual clinical expression of Hb H disease.

Anemia, Sickle Cell↗
PubMed1978

Membrane effects of imidoesters in hereditary stomatocytosis.

The marked increase in cation (Na+, K+) permeability that results in swollen, cup-shaped red cells in the hereditary stomatocytosis syndrome can be corrected in vitro with a bifunctional crosslinking reagent, dimethyl adipimidate (DMA). 45Ca influx in intact RBC, 45Ca efflux in red ghosts, and 45Ca retention in red ghosts are normal and not influenced by DMA. Endocytosis in resealed red ghosts is strikingly impaired but becomes normal if cells are first treated with 2 mM DMA. Protein kinase mediated phosphorylation of membrane proteins by AT32P--only 20--40% of normal control values in both shortterm (5 min) and more extended (60 min) incubations--is not improved by DMA. After reaction of 14C-DMA with stomatocytes, radiolabel is found associated with phosphatidyl serine and phosphatidyl ethanolamine and is also widely distributed among membrane proteins. Cation permeability of stomatocytes in corrected at DMA concentrations (1 mM) that result in barely detectable crosslinking of aminophospholipids or proteins, suggesting that either crosslinking of a minor component present in only small quantities or intramolecular (rather than intermolecular) crosslinking is responsible for the permeability effects. DMA, whose maximal crosslinking dimension is 7.3--9 A, is the most effective bifunctional imidoester of those tested. Shorter (dimethyl malonimidate) or longer (dimethylsuberimidate) reagents are either less effective than DMA or totally without effect.

Anemia, Hemolytic↗
PubMed1978

The influence of plasma bilirubin on zinc protoporphyrin measurement by a hematofluorimeter.

A fluorimeter has recently been developed to detect lead poisoning and iron deficiency by measuring erythrocyte ZPP directly from whole blood. Plasma bilirubin fluorescence has been found to influence this technique. ZPP levels determined by the fluorimeter were elevated by artificially increasing the plasma bilirubin concentration, both within and above the normal range, in whole blood samples. A rise in ZPP levels were also observed when the hemoglobin concentration was lowered by dilution with native plasma. When blood samples of patients with hyperbilirubinemia were analyzed, direct measurement of ZPP by this fluorimeter yielded significantly higher levels than did an alternate extraction method. Photodegradation of bilirubin in whole blood samples did not decrease fluorescent interference. Although the bilirubin measurably decreased, fluorescence increased following a 5 hr exposure to light.

Anemia, Sickle Cell↗
PubMed1977

Polyvalent pneumococcal-polysaccharide immunization of patients with sickle-cell anemia and patients with splenectomy.

To reduce the risk of infection from Streptococcus pneumoniae in hyposplenic patients we administered octavalent pneumococcal vaccine to 77 patients with sickle-cell disease and 19 asplenic persons and compared their response with 82 controls (38 age-matched normal persons and 44 normal black African children). Fifty micrograms each of pneumococcal-polysaccharide Types 1, 3, 6, 7, 14, 18, 19, and 23 were administered subcutaneously. Post-immunization serums (three to four weeks) were available from 52 of 77 patients with sickle-cell disease; the percent responding and the magnitude of the indirect hemagglutination response were comparable to those of the controls. Within two years after immunization we observed eight Str. pneumoniae infections in 106 age-matched unimmunized patients with sickle-cell disease, but none in the 77 immunized (P less than 0.025). We conclude that pneumococcal polysaccharides are immunogenic in hyposplenic patients and may protect against systemic Str. pneumoniae infection.

Adolescent↗
PubMed1977

An unusual form of chronic neutropenia in a father and daughter with hypogammaglobulinaemia.

Chronic neutropenia, with an abundance of mature neutrophils in the bone marrow, was discovered in a father and daughter who also had common variable hypogammaglobulinaemia. Under the stress of infection or following the administration of typhoid vaccine, release of neutrophils from the marrow was enhanced sufficiently to abolish neutropenia temporarily. Although their morphology was abnormal, the function of neutrophils in vitro was normal. Thus, the increased susceptibility to infection that characterized these patients appeared to be due primarily to their defect in humoral immunity rather than their neutropenia.

Adult↗
PubMed1976

Correction of the permeability defect in hereditary stomatocytosis by dimethyl adipimidate.

The effect of imidoesters on the extraordinarily increased cation permeability of hereditary stomatocytes was evaluated in erythrocytes from a splenectomized boy with persistent hemolytic anemia. Reaction of stomatocytes with dimethyl adipimidate reduced ouabain-associated potassium loss from 15 to 1.7 and sodium gain from 22 to 2.5 meq per liter of red cells per hours. Red-cell volume, cation concentration, and deformability, previously abnormal, rapidly became normal after stomatocytes were reacted with dimethyl adipimidate. Instead of stomatocytes, normal red cells and target cells were noted. The survival (half-time) of stomatocytes treated with 51Cr-labeled dimethyl adipimidate infused into rats rendered tolerant to human erythorocytes by pretreatment with ethyl palmitate and cobra-venom factor was double that of untreated stomatocytes. Chemical modification of the defect in vitro allowed stomatocytes to regain many properites of normal erythrocytes and favorably influenced the subsequent survival of these cells in vivo.

Adenosine Triphosphate↗
PubMed1976

Developmental change in red blood cell volume: implication in screening infants and children for iron deficiency and thalassemia trait.

The mean corpuscular volumen when determined by electronic counter is an accurate tool for identification of children with microcytosis due to either iron deficiency or thalassemia trait. The purpose of this report is to describe the normal developmental changes in MCV that occur in children afler 6 months of age. In 211 healthy infants and children screened to exclude those with borderline or overt iron deficiency, thalassemia trait, or hemoglobinopathy, we found that the lower limit of normal for MCV is 70 ft between 10 and 17 months of age and that there is a gradual increase of MCV with age; the lower limit is 74 between 1 1/2 and 4 years and 76 between 4 and 7 years. All of these values are well below the minimum adult level of 80 fl.

Anemia, Hypochromic↗
PubMed1976

Iron deficiency in an Eskimo village. The value of serum ferritin in assessing iron nutrition before and after a three-month period of iron supplementation.

The serum ferritin concentration, a new means of assessing iron nutrition, was utilized in conjunction with the hematocrit value, serum iron concentration, and total iron binding capacity to determine the effect of a three-month period of iron supplementation in a group of 146 Eskimo children in Chevak, Alaska. Before treatment, 41% of the children had concentrations of serum ferritin below normal, 18% had a subnormal serum transferrin saturation, and 26% were anemic. After supplementation, only 6% had a subnormal serum ferritin concentration. Despite this evidence of improved iron stores in the group as a whole, the prevalence of low serum transferrin saturation and of anemia remained high, 15% and 17%, respectively. These results could be explained by a high incidence of infection, which, like iron deficiency, is associated with anemia and a low serum transferrin saturation. We conclude that the serum ferritin determination reflected an improvement in iron nutrition that was not as readily apparent by other measurements, and that factors other than iron deficiency also played an important role in the mild anemia that was prevalent in Chevak.

Adolescent↗
PubMed1976

Differentiation of transient erythroblastopenia of childhood from congenital hypoplastic anemia.

Erythrocyte properties of patients with congenital hypoplastic anemia were compared to those of patients with transient erythroblastopenia of childhood. The MCV was less than 85 in all nine TEC patients studied and greater than 90 in all 11 CHA patients. Hemoglobin F concentration was elevated beyond the normal level for age in eight CHA patients and almost always normal in TEC. The i antigen score was more likely to be elevated in CHA than in TEC. The activities of transaminase, aldolase, phosphofructokinase, and glutathione peroxidase were higher in CHA than in TEC (p less than 0.001). Some abnormal properties (namely, MCV and hemoglobi n F concentration) of CHA erythrocytes, present during remission but accentuated during relapse, seemed to vary with changes in serum erythropoietin. Early differentiation of TEC and CHA appears feasible, allowing prompt provision of a favorable prognosis and the avoidance of unnecessary corticosteroid therapy in TEC.

Adolescent↗