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Biomedical subjects

D A Sears

Publications and source records attributed to D A Sears.

At least 37 records · Page 2Linked to original sources
PubMed1986

Bone marrow histiocytic hyperplasia and hemophagocytosis with pancytopenia in typhoid fever.

Typhoid fever was associated with pancytopenia in five patients. Bone marrow examinations revealed histiocytic hyperplasia with marked phagocytosis of platelets, leukocytes, and red blood cells in these individuals. This phagocytosis may contribute to the pancytopenia that occurs in some patients with typhoid fever. The striking degree of the histiocytic hemophagocytosis is reminiscent of the malignant disease, histiocytic medullary reticulosis. The importance of careful exclusion of infectious etiologies in illnesses involving marrow histiocytic proliferation is emphasized.

Adolescent↗
PubMed1985

Splenic infarction, splenic sequestration, and functional hyposplenism in hemoglobin S-C disease.

Splenic atrophy or evidence of hyposplenism occurs in as many as one third of all patients with S-C hemoglobinopathy. Yet there are few reports in the literature of clinically apparent splenic infarction in this disease. We describe four instances of acute splenic infarction in three patients with hemoglobin S-C disease which illustrate a wide spectrum of clinical manifestations and severity. Of particular interest were the observations of coincident occurrences of splenic sequestration and functional hyposplenism with splenic infarction, suggesting a close pathophysiological relationship among these syndromes.

Adult↗
PubMed1983

Membrane-bound hemoglobin in the erythrocytes of sickle cell anemia.

The thoroughly washed ghosts of erythrocytes from normal subjects and patients with sickle cell anemia were assayed for their content of total protein, total globin, hemoglobin, and alpha and beta chains by chemical and electrophoretic techniques. Total protein, globin, and hemoglobin were significantly greater in sickle cell than in normal ghosts. Ghosts prepared from different density fractions of sickle red cells showed no significant differences in protein, globin, or hemoglobin, though membrane-bound globin was highest in the most dense cells. In both whole populations and density fractions of sickle red cells, the majority of the membrane-bound globin retained its heme. Alpha and beta S chains were present in equal amounts in the sickle cell membranes.

Anemia, Sickle Cell↗
PubMed1982

Increased Ca++, Mg++, and Na+ + K+ ATPase activities in erythrocytes of sickle cell anemia.

To determine whether diminished activity of the Ca++ extrusion pump could account for the high levels of red blood cell (RBC) Ca++ in sickle cell anemia (SS), we measured calmodulin-sensitive Ca++ ATPase activity in normal and SS RBC. Hemolysates prepared with saponin were compared, since such preparations expressed maximum ATPase activities, exceeding isolated membranes or reconstituted systems of membranes plus cytosol, SS RBC hemolysates had greater Ca++ ATPase activity than normal hemolysates; they exhibited higher Mg++ and Na+ + K+ ATPase activities as well. Assays on density (age) fractions of SS and normal red cells demonstrated that all ATPase activities were highest in low density (young) cells, and activities in SS red cells exceeded those in normals in all fractions studied. Thus, when studied under conditions that maximize enzyme activity, Ca++ ATPase activity, like Mg++ and Na+ + K+ ATPase, is actually increased in SS RBC, probably due to the young red cell population present. The elevated Ca++ levels in these cells are more likely due to an increased Ca++ leak or abnormal calcium binding than to defective extrusion by the ATPase pump.

Adenosine Triphosphatases↗
PubMed1981

Ulcerative colitis complicated by autoimmune hemolytic anemia.

We have reported the rare association of severe autoimmune hemolytic anemia with active ulcerative colitis, and added to the sparse published recommendations concerning management. Although aggressive medical therapy resulted in only partial control of the inflammatory bowel disease and hemolysis, both disorders remitted rapidly after panproctocolectomy and splenectomy. Autologous red cells were safely transfused during surgery.

Adult↗
PubMed1981

Bernard-Soulier disease: a study of four patients and their parents.

Two families with Bernard-Soulier disease, including four patients and three of their parents, were studied and detailed clinical summaries are presented. One patient in each family has suffered severe bleeding problems while the other affected sibling is less severely affected. There has been no excessive bleeding in any of the parents or other family members. The patients demonstrated the abnormalities characteristic for Bernard-Soulier disease: thrombocytopenia, giant platelets, prolonged bleeding time, abnormal platelet aggregation to human FVIIIvWF and ristocetin or bovine FVIIIvWF alone, defective ristocetin-induced binding of human 125I-FVIIIvWF multimers, decreased platelet lysis by a drug-dependent antibody and complement, and a decreased concentration of membrane glycoprotein I. The parents had normal platelet counts, bleeding times, and FVIII-mediated aggregation. However, the parents had abnormally large platelets decreased sensitivity to lysis by a drug-dependent antibody and complement, and a decreased concentration of membrane glycoprotein I. Therefore the heterozygous state for Bernard-Soulier disease is recognizable by platelet membrane abnormalities although there is no defect of platelet function and no excessive bleeding. Red cell membrane proteins of one patient were normal, suggesting that phenotypic expression of the Bernard-Soulier disease defect is restricted to platelets.

Adolescent↗
PubMed1980

Measurement of hemoglobin chains bound to the erythrocyte membrane. Development of a method and studies of incubated normal cells.

A method utilizing sodium dodecyl sulfate--polyacrylamide gel electrophoresis for the sepration of the alpha and beta chains of hemoglobin has been adapted to quantify hemoglobin chains by simultaneous electrophoresis of globin standards with unknowns, staining with Coomassie blue, densitomeric scanning, and planimetry. This method has been used to quantify the globin chains bound to the human red cell membrane during sterile incubation and ATP depletion in vitro. In thoroughly washed (6-step) ghosts of incubated cells; (1) more beta than alpha chains were bound (beta/alpha ratio 1.28); (2) only about one third of the bound chains contained heme; and (3) globin accounted for less than 20% of the "excess" protein present in the incubated cells compared to fresh cells. Four-step ghosts contained more hemoglobin, a smaller proportion of heme-free alpha and beta chains, and approximately equal numbers of alpha and beta chains (beta/alpha ratio 1.09).

Electrophoresis, Polyacrylamide Gel↗
PubMed1978

Effects of pH and temperature on the interaction of an impermeant probe with surface proteins of the human red blood cell.

The conformation of the outer surface of the human red cell membrane has been studied under various conditions using the impermeant probe [125I]diazodiiodosulfanilic acid. At least seven polypeptides were labeled by the reagent, including the three extractable glycoproteins separable by the electrophoretic method employed. The Mr = 43,000 protein band was shown to contain two labeled species, one a glycoprotein, in addition to its major constituent, red cell actin. The extent and pattern of labeling were very sensitive to changes in pH and temperature. Total labeling increased with increasing pH and was greater at 4 degrees C than 37 degrees C. Binding of the probe to the Mr = 90,000 polypeptide and the major glycoprotein were relatively increased with increasing pH and temperature while opposite effects were observed for the Mr = 43,000 peptide(s). The pH effects on external membrane labeling were rapidly reversible. Results were similar in cells of different densities, suggesting that the pH and temperature effects were not related to cell age. The data presented emphasize the lability of membrane conformation and reactivity and thus the necessity to consider carefully the conditions of labeling in interpretation of studies using impermeant probes.

Erythrocyte Membrane↗
PubMed1977

Topography of the external surface of the human red blood cell membrane studied with a nonpenetrating label, [125I]diazodiiodosulfanilic acid.

The topography of the external surface of the human red cell membrane has been studied using an impermeant radioactive probe, [125I]diazodiiodosulfanilic acid, which binds covalently to protein groups of the membrane following reaction with intact cells. The pattern of labeling was assessed by sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis followed by sequential analysis of single gels for carbohydrates (by staining with the periodic acid-Schiff (PAS) reagent), for proteins (by staining with Coomassie blue), and for radioactivity (by counting gels sliced in 2-mm segments). The radioactive probe bound to membrane polypeptides with apparent molecular weights of 94,200, 58,100, and 46,500 (Peaks A, B, and C, respectively). Peak A co-migrated with a small periodic acid-Schiff-positive band and protein Band 3 (nomenclature of Steck) (Steck, T.L. (1974)J. Cell Biol. 62: 1-19). Peak B migrated with protein Band(s) 4.5 slightly ahead of the major membrane glycoprotein (PAS-1). Peak C migrated like glycoprotein PAS-2 and protein Band 5, the actin-like, water-soluble membrane protein. In contrast to lactoperoxidase iodination and a number of other probes, [125I]diazodiiodosulfanilic acid reacted minimally with the major membrane glycoprotein, glycophorin. When it was reacted with isolated ghosts, all molecular weight classes of polypeptides were labeled. Treatment of labeled cells with neuraminidase or trypsin altered the glycoprotein staining pattern, but not the radioactive peaks. On the other hand, Pronase eliminated the Mr=94,200 radioactive peak, diminished the other two radioactive peaks, and profoundly changed the glycoprotein and protein staining patterns. Treatment of the membranes of labeled cells in a low ionic strength alkaline medium did not alter radioactive peaks and demonstrated that Peak C differed from the actin-like membrane protein. A nonionic detergent, Triton X-100, solubilized all radioactive components. The studies have defined the binding of [125I]diazodiiodosulfanilic acid to external proteins of the human red cell membrane. Its pattern of reaction differs quantitatively and qualitatively from other commonly used reagents, and it provides a useful additional vectorial probe for the study of membrane topography. Its reactions provide further evidence of the organizational complexity of the red cell membrane and emphasize the fact that interpretation of information derived from the use of membrane probes must take into account the differences resulting from the properties of the probing reagents themselves.

Azo Compounds↗
PubMed1977

Development of chronic myelocytic leukemia during the course of acute lymphocytic leukemia in an adult.

A 59-year-old patient is described who presented with acute lymphocytic leukemia. Complete remission was induced rapidly with vincristine and prednisone. Nine months later he acquired the clinical and hematological picture of a myeloproliferative disease, and bone marrow cytogenetic studies demonstrated the presence of the Philadelphia chromosome. Within 4 months he again developed overt acute lymphocytic leukemia and died. Several lines of evidence have recently indicated a relationship between myeloproliferative and lymphoproliferative disorders, particularly chronic myelocytic and acute lymphocytic leukemia. This patient's course is another example of that association.

Bone Marrow↗
PubMed1976

Histiocytic medullary reticulosis with parallel increases in serum acid phosphatase and disease activity.

Two months after presenting with autoimmune hemolytic anemia, a 57-year-old man developed increased serum acid phosphatase activity. Subsequently, abnormal histiocytes were found in the bone marrow and blood, and 8 months after the onset of his illness lymph node biopsy led to the diagnosis of histiocytic medullary reticulosis. At that time the level of serum acid phosphatase activity was more than 60 times the upper limit of normal and then paralleled the activity of his disease during temporary responses to chemotherapy, rising to over 90 times normal at the time of his death 1 year after presentation. No prostatic malignancy was demonstrated by biopsies or at autopsy, and electrophoretic studies of the serum enzyme suggested that it was of extraprostatic origin. It is postulated that the acid phosphate present in the serum at levels heretofore described only in metastatic carcinoma of the prostate may have arisen from the abnormal histiocytes.

Acid Phosphatase↗
PubMed1976

Remission induction in adult acute lymphocytic leukemia. Use of vincristine and prednisone alone.

Therapy for acute lymphocytic leukemia (ALL) has been less successful in adults than in children. Many centers treat all adult leukemia with the same regimen. We have used vincristine and prednisone for initial therapy in 14 adults with ALL since 1971 and have followed a treatment regimen developed for childhood ALL for subsequent therapy as well. Complete remissions were attained in 13, and complications and duration of hospitalization were minimized with this nonmyelotoxic regimen. Central nervous system "prophylactic" therapy was also well tolerated in these adult patients. However, remission duration and survival in our series were similar to those reported by others. That complete remission can be attained in a high percentage of adult patients with ALL through use of relatively nontoxic treatment demonstrates the importance of selecting out this group of patients from all adults with acute leukemia.

Adolescent↗
PubMed1976

Studies on platelet plasma membranes. I. Characterization of surface proteins of human platelets labeled with diazotized (125i)-diiodosulfanilic acid.

A polar, nonpenetrating compound of high specific activity, diazotized (125I)-diiodosulfanilic acid (DD125ISA), has been developed as a label for exposed proteins of the human platelet plasma membrane, and platelet proteins and the pattern of labeling have been studied with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). That DD125ISA binds specifically to membrane proteins was demonstrated by: (1) the specific activity of isolated membrane protein was five to seven times that of whole platelet protein and (2) no proteins of intact platelets were labeled which were not represented in the isolated plasma membrane. That the DD125ISA-labeled membrane proteins were exposed on the cell surface was demonstrated by: (1) DD125ISA-labeled proteins were altered by trypsin treatment of intact, labeled platelets and (2) the pattern of labeling produced by reaction of isolated membranes with DD125ISA was quite different from that produced by the labeling of intact platelets. Analysis of platelet membrane proteins by SDS-PAGE demonstrated the glycoproteins previously described at 150,000 daltons (termed glycoprotein I) and 92,000 daltons (glycoprotein III) but we could discriminate two apparently distinct glycoproteins in the intermediate region (IIa: 125,000 daltons, and II: 118,000 daltons). Glycoproteins I and III were constant whereas IIa was clearly visible only in unreduced samples and II was predominant in reduced samples. Reaction of DD125ISA with intact platelets resulted in equal labeling of three of these four membrane glycoproteins (IIa, II, and III). The pattern of exposed proteins on the platelet surface labeled by DD125ISA was different from lactoperoxidase-131I, which labeled predominantly the 92,000 dalton glycoprotein, as demonstrated by simultaneous SDS-PAGE analysis. Therefore three glycoproteins of the human platelet plasma membrane are exposed to a radioisotope probe on the platelet surface and are accessible for contact interactions.

Azo Compounds↗