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Biomedical subjects

D A Sears

Publications and source records attributed to D A Sears.

At least 55 records · Page 3Linked to original sources
PubMed1976

Studies on platelet plasma membranes. II. Characterization of surface proteins of rabbit platelets in vitro and during circulation in vivo using diazotized (125i)-diiodosulfanilic acid as a label.

Diazotized (125I)-diiodosulfanilic acid (DD125ISA) binds specifically to the exposed proteins on the surface of the rabbit platelet plasma membrane. This was demonstrated by the following observations with the use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of whole platelets and the isolated plasma membrane fraction: (1) the specific activity of isolated membrane protein was sevenfold that of whole platelet protein, (2) no proteins of intact platelets were labeled which were not represented in the isolated plasma membrane, (3) DD125ISA-labeled proteins were altered by trypsin treatment of intact, labeled platelets, and (4) the pattern of labeling produced by reaction of isolated membranes with DD125ISA differed from that produced by the labeling of intact platelets. Reaction of DD125ISA with intact platelets produced labeling of only the three membrane glycoproteins (molecular weights: 180,000, 125,000, and 92,000 daltons) with greatest labeling of the largest glycoprotein and least labeling of the smallest glycoprotein. When rabbit platelets were labeled simultaneously with DD125ISA and 51Cr, the two isotopes were similarly distributed in various density populations of platelets. Some DD125ISA was solubilized from labeled and washed platelets by sonication, but all platelet DD125ISA was recovered in the plasma membrane fraction after 30 minutes' circulation in vivo. In vivo 51Cr recovery and survival were not altered by simultaneous labeling of platelets with DD125ISA. The disappearance of DD125ISA from circulating platelets (T 1/2 = 17 hours) was more rapid than 51Cr (T 1/2 = 30 hours) and appeared exponential in contrast to the linear 51Cr disappearance. On the other hand, DD125ISA did not disappear from platelets faster than 51Cr when doubly labeled platelets were harvested after 3 hours' circulation and incubated in autologous plasma (T 1/2 of DD125ISA elution = 43 hours, 51Cr = 33 hours). SDS-PAGE analysis of DD125ISA-labeled platelets after 14 to 20 hours' circulation in vivo demonstrated the same pattern of DD125ISA distribution on membrane glycoproteins as on the platelets prior to infusion. We interpret this symmetrical loss of the membrane label to indicate symmetrical loss of membrane proteins, suggesting that the platelet may lose pieces of membrane and not specific surface proteins during circulation. This could occur during reversible adhesion encounters during the process of hemostasis and cause the smaller size and decreased effectiveness of older platelets.

Animals↗
PubMed1975

Leukaemoid reactions in myeloproliferative diseases. Report of two patients.

The occurrence of transient extreme neutrophilic leucocytosis, with white blood cell counts exceeding 100,000/mu-l in two adult patients with myeloproliferative diseases, polycythaemia vera and acute myelocytic leukaemia in remission, is reported. The reaction was transient, and the subsequent course of the patient's disease did not differ from that prior to the episode. Such extreme leucocytosis is rare in adults, despite the frequency of provoking conditions, and factors which predispose an individual to develop a leukaemoid reaction remain unknown. An increase in the size of the pool of proliferating granulocyte precursors accompanied by a loss of the restraining function of the marrow sinusoidal walls in myeloproliferative diseases may explain the augmented release of myeloid cells in our patients.

Female↗
PubMed1975

Studies on pure red cell aplasia. VII. Presence of proerythroblasts and response to splenectomy: a case report.

An 18-yr-old female with chronic active hepatitis developed a severe anemia due to a lack of red cell production. Her bone marrow showed many large proerythroblasts but an almost complete lack of more mature erythroblasts. Incubation of the marrow cells in a normal medium with erythropoietin concentrate led to increased erythropoiesis as indicated by the development of mature erythroblasts as well as a ninefold increase in hemoglobin synthesis. The patient's plasma was cytotoxic for erythroblasts. Following splenectomy, a remission of the disease occurred. This study indicates that in some cases the anemia associated with abundant marrow proerythroblasts and the absence of mature erythroblasts has the same pathogenesis as pure red cell aplasia and that splenectomy may be beneficial when there is a lack of response to immunosuppressive drugs.

Adolescent↗
PubMed1975

Transient red blood cell aplasia in association with viral hepatitis. Occurrence four years apart in siblings.

Transient pure red blood cell aplasia was verified during the course of viral hepatitis in two siblings whose illnesses occurred four years apart. The duration and course of the anemia was very similar in the two subjects, and in both the hepatitis progressed to a chronic active form. Autoimmune phenomena were prominent in one patient and suggested in the other, but a cytotoxic antibody to erythroblasts could not be demonstrated in the one patient in whom it was sought. The unique occurrence of such a syndrome in siblings, widely separated in time, suggests the possibility of a genetic predisposition governing the unusual response to a common illness.

Adult↗
PubMed1975

Binding of intracellular protein to the erythrocyte membrane during incubation: the production of Heinz bodies.

During sterile incubation of normal human erythrocytes at 37 degrees C., intracellular nonhemoglobin protein is bound to the membrane prior to hemolysis. These studies have characterized this phenomenon further. Protein binding to the membrane began after 12 hours incubation when cellular ATP was depleted and increased to 36 hours incubation. The binding was prevented by adding adenosine or glucose at the start of incubation and was arrested by adding adenosine to regenerate ATP during the course of incubation. However, protein, once bound, was not released by regeneration of ATP. The amount of protein bound was not altered by: (1) addition of Ca++ or EDTA to the medium, (2) blockade of sulfhydryl groups with N-ethylmaleimide, or (3) stabilization of heme-globin bonds by conversion of hemoglobin to cyanmethemoglobin. Conversion of hemoglobin to carboxyhemoglobin by incubations under carbon monoxide inhibited protein binding, but this appeared to be an effect of exclusion of oxygen rather than stabilization of heme-globin bonds since incubation under nitrogen had a similar effect. The morphological counterpart of this chemically-measured membrane-bound protein was visible in red cell ghosts stained with crystal violet as small membrane-associated particles resembling Heinz bodies. Sodium dodecyl sulfate acrylamide gel electrophoresis of membranes of incubated cells revealed a new protein band that was identical to globin monomers. This membrane binding of globin during incubation provides a model for the study of Heinz body formation in clinical disorders.

Adenosine↗
PubMed1970

Disposal of plasma heme in normal man and patients with intravascular hemolysis.

The clearance of plasma protein-bound heme, its sites of removal, and the reutilization of hemeiron were studied by radioisotopic techniques in normal human subjects and in patients with intravascular hemolysis. In normal subjects, injected heme-(59)Fe was bound immediately by albumin and the beta(1)-globulin, hemopexin. Its clearance from the plasma was descr bed by a single exponential equation, and the half-life in plasma was 7-8 hr. Removal was largely by the liver. Iron reutilization began promptly, and half the injected heme-iron was incorporated into circulating red cells within one cell life-span. In patients with intravascular hemolysis, hemopexin was depleted, and injected heme was bound solely to albumin. Plasma clearance was described by a double exponential equation of the form: y = Ae(-k1t) + Be(-k2t). The half-lives of the two components averaged 3.9 and 22.2 hr, respectively. Removal was by the liver in at least some of the patients, and iron reutilization was variable, depending on the state of body iron stores. When hemopex'n was depleted in a normal subject by repeated heme injection, clearance mimicked that observed in the patients.

Beta-Globulins↗