bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of bovine factor viii‐induced guinea pig platelet aggregation by simple sugars and derivatives
Authors: Kuwahara Steven S. , Malik Michael
Published: February 2007

Working with the hypothesis that the binding of carbohydrate groups is important in the induction of platelet aggregation by bovine factor VIII, we studied 36 different sugars and sugar derivatives for their ability to inhibit the aggregation of guinea pig platelets. Concentrations that produced 50% inhibition of the aggregation response ranged from 232 mM (galactose) to 12 mM (glucosamine and galactosamine). Using these values, we found that several factors affected the ability of sugar structures to inhibit bovine factor VIII‐induced aggregation of guinea pig platelets. In general, galactose and its derivatives were not as effective as glucose and its derivatives. Sugars possessing α‐glycosidic linkages tended to be stronger inhibitors than those having β‐linkages. Polyols were better inhibitors than their corresponding aldoses. D‐fucose (129 mM) was a weaker inhibitor than L‐fucose (66 mM), but D‐and L‐arabinitol were not significantly different. N‐acetylation of glucosamine reduced its ability to inhibit aggregation. The number of free hydroxyl groups in a molecule did not appear to be a significant determinant of its ability to inhibit aggregation.

The results support the hypothesis that a binding site for carbohydrate groups exists either on the platelet membrane or on the bovine factor VIII molecule. The binding of the carbohydrate to this site is an important step in the induction of aggregation, and this binding site is relatively specific for the carbohydrate structures that it will accept.
Determination of antiplatelet antibody activity in sera cytotoxic for human lymphocytes
Authors: Colman Robert W. , Busch George J.
Published: February 2007

Pooled serum aliquots obtained from sensitized potential renal allograft recipients on chronic hemodialysis were evaluated for their lymphocytotoxicity titers against the lymphocytes and then for alloantibodies against the platelets of 7 random donors by 5 methods. Platelet donor specific lymphocytotoxicity was present in 93% of 42 combinations. Of the positive combinations, 57% had a positive test for antiplatelet activity by the 14C serotonin release assay, 16% by the platelet aggregation method, and 19% as judged by acid phosphatase availability on the platelet membrane. No serum tested released β‐glucoronidase or lactic dehydrogenase. No correlation of the height of the titer of antiplatelet activity with that for lymphocytoxicity was detected. Thus, even in sera demonstrating significant activity against donor lymphocyte antigens, detection of associated platelet antibody activity is not uniform. Thus, a positive lymphocytoxic titer does not necessarily predict detectable antiplatelet activity. Therefore, additional tests for detection of antiplatelet activity should also be considered. This study shows that of the tests evaluated, the 14C serotonin release assay is the most sensitive for detection of antiplatelet antibodies.
In vivo leukemic transformation: Cytogenetic evidence of in vivo leukemic transformation of engrafted marrow cells
Authors: Goh Kong‐Oo , Klemperer Martin R.
Published: February 2007

A 4‐year‐old girl with acute myeloblastic leukemia was treated with 50 mg/kg cyclophosphamide daily for 4 days before being given 1.7 × 108 bone marrow cells/kg from her HL‐A identical, MLC nonreactive, cytogenetically normal brother. The patient died 92 weeks after the marrow graft. Postmortem examination showed increased myeloblasts and promyelocytes. Cytogenetic studies before transplantation showed that all sex determination metaphases had an XX pattern, and 41% of the hyperdiploid metaphases had an additional 19–20(F) chromosome. At autopsy all hyperdiploid metaphases with XY pattern and 43% of the hyperdiploid metaphases with an XX pattern had an additional F chromosome. Occasional metaphases with 47,XX,+F or 47,XY,+F were seen during the follow‐up studies. These findings indicated that an acute leukemia had developed in the XY cell line of this artifically induced sex chimeric child. This suggests that a leukemic stimulus other than that proposed to be induced by total‐body irradiation existed in this patient and transformed the engrafted cells.
Erythrocytic glutathione reductase deficiency in a hospital population in the united states
Authors: Frischer Henri
Published: February 2007

In the USA, erythrocytic glutathione reductase (GSSG‐R) deficiency is significantly more common, and can be considerably more pronounced in hospitalized patients (118/3198) than in outpatients (37/1639) or in apparently healthy persons (12/849). Retrospective analysis of illnesses found in 118 inpatients with erythrocytic GSSG‐R deficiency revealed a striking and previously unsuspected association of the enzyme deficiency with a variety of chemotherapeutically treated hematological or nonhematological malignancies (51/118 patients, 43.2%, or 51/170 diagnoses, 30.0%). The prevalence of erythrocytic GSSG‐R deficiency also increased in malnutrition, liver disease, and sepsis. Drugs of the nitrosourea class, particularly BCNU [1, 3‐bis(2‐chloroethyl)‐1‐nitrosourea] are causally implicated in the association of GSSG‐R deficiency with malignancies. Severe or complete GSSG‐R deficiency may handicap host response to infections.
Secondary gout in hemoglobinopathies: Report of two cases and review of the literature
Authors: Ballou Stanley , Khan Muhammad A. , Kushner Irving , Harris John W.
Published: February 2007

Although patients with hemolytic hemoglobinopathies characteristically are over‐producers of urate, and hyperuricemia is frequently recognized, clinical gout has rarely been reported in such patients. Our evaluation of 2 premenopausal women with gout led to the diagnosis of previously unrecognized hemoglobinopathies (SC disease and CC disease). Investigation of these 2 patients and review of the reported cases of gout in patients with hemoglobin S or C disorders suggest that relatively minor abnormalities of renal function in these patients may lead to early development of significant hyperuricemia. With increasing lifespan of patients with hemolytic hemoglobinopathies and the likelihood of increased occurrence of renal function abnormalities, it is anticipated that gout will more frequently be responsible for joint symptoms in such patients.
Cytotoxicity of a factor from normal and abnormal human spleens for allogenic leukemia cells
Authors: Lozzio Bismarck B. , Lozzio Carmen B. , Bamberger Elena G.
Published: February 2007

A search for an endogenous cytotoxic factor (ECF) was made by analyzing 103 spleens from normal humans and patients suffering from hematopoietic malignancies, solid tumors, inflammatory diseases, and congestive and hyperplastic splenomegalies. A highly purified ECF was obtained by a combination of gel filtration and ion‐exchange column chromatography. The factor is a low‐molecular‐weight (< 2,000) substance and is probably a peptide or peptide‐nucleotide complex. The biologic activity of the ECF was assayed on myelogenous and lymphatic leukemia cells of human origin. The spleens from normal individuals produced and/or stored the largest quantity of the ECF. The amount of ECF extractable from the pathologic spleen was drastically diminished regardless of the disease or therapeutic regimen. The ECF was significantly more cytotoxic for lymphatic than for myelogenous leukemia cells.
Acute lymphoblastic leukemia–hand mirror cell variant: A detailed cytological and ultrastructural study with an analysis of the immunologic surface markers
Authors: Stass Sanford A. , Perlin Elliot , Jaffe Elaine S. , Simon David R. , Creegan W. J. , Robinson J. J. , Holloway M. L. , Schumacher Harold R.
Published: February 2007

Acute lymphoblastic leukemia was observed in a 22‐year‐old white female patient and was manifested by normal platelet counts, 50–60% hand mirror cells (HMC) in the bone marrow, and prolonged survival without treatment. The characteristic neoplastic cell had a nucleus within the “mirror” portion and a cytoplasmic uropod forming the “handle” portion. The presence of acid phosphatase and B‐glucuronidase activity suggested that the cell was a T cell lymphoblast. However, extensive immunologic surface marker studies indicated the cells were non‐T, non‐B. Terminal transferase activity further supported the lymphoid nature of the cell. The hand mirror cells were considered a real phenomenon since they were demonstrated on phase contrast microscopy, scanning electron microscopy, and transmission electron microscopy. The cells did not grow in tissue culture and cytogenetics revealed a normal female karyotype. From the above observations, the HMC is a lymphoblast with morphological, cytochemical, and immunological features which may differentiate it from the usual cell in acute lymphoblastic leukemia. Therefore, cases involving increased numbers of hand mirror cells in the bone marrow and acute lymphoblastic leukemia require further investigation to elucidate the full importance of this cell. This study represents the first attempt to investigate this cell in detail.
Sequential pure red cell and megakaryocyte aplasia associated with chronic liver disease and ulcerative colitis
Authors: Fox Richard M. , Firkin Frank C.
Published: February 2007

The clinical course of a patient with chronic hepatitis and previous ulcerative colitis who subsequently developed pure red cell aplasia (PRCA) is described. The PRCA remitted initially with corticosteroid therapy. A subsequent relapse responded to cyclophosphamide therapy following splenectomy. This was followed by a fatal third episode of red cell aplasia associated with megakarocyte aplasia.
Abnormalities of the peripheral blood as a presenting feature of immunodeficiency
Authors: Blanchette Victor S. , Hallett Jospeh J. , Hemphill J. Michael , Winkelstein Jerry A. , Zinkham William H.
Published: February 2007

The predisposition of immunodeficient patients to the development of peripheral blood abnormalities is well documented. Less often recognized is the presence of immune defects in patients who initially present with “idiopathic” forms of thrombocytopenic purpura or autoimmune hemolytic anemia in the absence of symptomatology indicative of an immunodeficiency. In this report we describe two children, each of whom had intermittent and at times severe hemolysis and thrombocytopenia secondary to formation of autoantibodies. Although the initial clinical impression was the presence of an “idiopathic” form of platelet or red cell destructive phenomenon, subsequent observations demonstrated abnormalities of the immune system which affected both B and T lymphocytes. In one of the patients there was a marked deficiency of IgA with a moderate but progressive decrease in IgM and IgG. The other patient had a moderate decrease in IgA and a failure to sensitize to dinitrochlorobenzene. Both exhibited dysmorphic features, including small stature, abnormal dentition, hyperelasticity of the skin, and hyperextensibility of the joints. Neither had significant problems with bacterial, fungal, or viral infections. These observations highlight the importance of evaluating the immune system in children with “idiopathic” forms of hemolytic anemia or thrombocytopenia. Demonstration of these abnormalities can have important therapeutic implications and may also provide information regarding the etiology of the blood abnormalities.
Granulocytic colonies on macrophage‐coated membranes
Authors: Turner A. R. , Pfrimmer W. J. , Torok‐Storb B. J. , Boggs D. R.
Published: February 2007

A macrophage cell coating covering a cellulose acetate disk was an effective microenvironment for the production of peroxidase‐positive hematopoietic colonies. These developed after intraperitoneal injection of marrow cells with a linear cell relationship of dose to colonies formed. One colony formed for every 2,000 nucleated marrow cells injected. Observation of colony formation daily showed a steady increase in number and size until seven days after cell inoculation. X‐irradiation (400 rads) eliminated intrinsic colony formation in BALB/c mice. Irradiation of the donor of the ip marrow cells resulted in a Do of 95 rads. Treatment of the marrow donor with cytosine arabino‐side had a suppressive effect on colony formation as did treatment of the host animal after receipt of the ip marrow. These results indicate that the precursor of the granulocytic colonies seen in the macrophage layers are more similar to committed granulocytic precursors than to the pluripotential stem cell.
Platelet satellitism—An ultrastructural study
Authors: Skinnider L. F. , Musclow C. E. , Kahn W.
Published: February 2007

Ultrastructural studies by scanning and transmission electron microscopy were carried out on one of four cases of platelet satellitism. Adherence to the neutrophils was mainly by focal contact between small surface projections of the platelets and neutrophils. Phagocytosis was not seen with the neutrophils but was evident in the monocytes. The degree of satellitism noted increased with the time the blood anticoagulated with EDTA was left at room temperature. Mixing experiments with a patient's plasma and control cells and the patient's cells and control plasma were inconclusive but suggested that the abnormality may reside in the plasma.
Corticosteroid‐induced lymphocytopenia in man: Absence of splenic influence and effect of recipient serum
Authors: Beardsley G. Peter , Cohen Harvey Jay
Published: February 2007

Pharmacologic doses of corticosteroids produce a profound, transient lymphocytopenia in man. We have studied the role of the spleen and possible induction of cytolytic factors in the generation of this effect. A 200 mg IV dose of hydrocortisone‐21‐hemisuccinate was administered to five normal subjects and five subjects whose spleens had been removed as a result of trauma. Sequential peripheral blood lymphocyte counts and subpopulations were then determined, and the effect of serum (obtained from the recipients at several time points after steroid administration) on autologous lymphocyte viability was assessed in vitro. The asplenic subjects experienced the same marked lymphocytopenia as normal individuals, and post‐steroid serum was not cytotoxic to autologous lymphocytes. The in vitro results support the view that corticosteroid‐induced lymphocytopenia is not the result of lymphocytolysis in man. If lymphocyte redistribution is the cause, as has been suggested, our in vivo results directly demonstrate that the spleen does not play a major role.
Lactic acidosis and diffuse histiocytic lymphoma (DHL)
Authors: Mintz Uri , Sweet Donald L. , Bitran Jacob D. , Ultmann John E.
Published: February 2007

Four patients with advanced diffuse histiocytic lymphoma who developed lactic acidosis are described. All four patients demonstrated disturbed liver function tests. In two of the patients, the lactic acidosis was unresponsive to treatment. The third patient responded successfully to the early initiation of combination chemotherapy with achievement of a clinical remission and correction of the lactic acidosis. The fourth patient responded to the initiation of chemotherapy with abatement of his lactic acidosis, but expired probably as the result of a pulmonary embolus. It seems likely that extensive hepatic infiltration may be one of the factors contributing to lactic acidosis in patients with diffuse histiocytic lymphoma. The early initiation of antineoplastic therapy may be important in the mangement of patients with histiocytic lymphoma and lactic acidosis.
Studies on a new variant of the Hermansky‐Pudlak syndrome: Qualitative, ultrastructural, and functional abnormalities of the platelet‐dense bodies associated with a phospholipase a defect
Authors: Rendu Francine , Breton‐Gorius Jeanine , Trugnan Germain , Castro‐Malaspina Hugo , Andrieu Jean‐Marie , Bereziat Gilbert , Lebret Marilyne , Caen Jacques P.
Published: February 2007

The structure and functions of platelets from a patient in whom albinism and hemorrhagic diathesis were associated have been investigated. Electron microscope studies showed a large reduction in the number of dense bodies and this was confirmed by an examination of fluorescent platelets loaded with mepacrine. The rare dense bodies were much bigger than normally observed; their density was diminished and was localized in a peripheral ring. Other platelet constituents were found to be normal. Platelet peroxidase activity was normal in the canaliculi of the dense tubular system; catalase‐positive granules were also present. Serotonin uptake by the patient's platelets was much decreased and reserpine, a potent inhibitor of serotonin accumulation by normal human platelets, did not further decrease this incorporation. The uptake of free 14C‐arachidonic acid by the platelets was greatly diminished, as was its thrombin‐induced liberation from phosphatidylcholine and phosphatidyl inositol. Moreover, platelet phospholipase A1 activity was much reduced and phospholipase A2 activity was undetectable.
Circulating inhibitors of blood coagulation associated with procainamide‐induced lupus erythematosus
Authors: Davis Stephen , Furie Barbara C. , Griffin John H. , Furie Bruce
Published: February 2007

We studied a patient being treated with procainamide in whom we observed a high antinuclear antibody titer and prolonged activated partial thromboplastin (PTT), prothrombin (PT), and Stypven times (ST). Serum antibody concentrations against single‐stranded DNA were elevated while those against native DNA were not elevated, suggesting the procainamide‐induced lupus syndrome. Dilution of the patient's plasma with normal plasma failed to correct the PTT and PT, indicating the presence of an inhibitor(s) to blood coagulation. The anticoagulant activity was associated with the IgG fraction of the patient's serum. Addition of purified or partially purified human factors IX, X, VIII, VII, XIa, prekallikrein, high molecular weight kininogen, or phospholipids to the patient's plasma failed to correct the PTT, PT, or ST; however, purified human factor XII and prothrombin corrected the PTT and ST, respectively. These results indicate that production of antibodies directed against antigenic determinants on coagulation proteins can be a manifestation of procainamide‐induced lupus erythematosus.
The “Hageman” connection: Interrelationships of blood coagulation, fibrino(geno)lysis, kinin generation, and complement activation
Authors: Murano Genesio
Published: February 2007

The activation pathways for the generation of enzymes involved in blood clotting, clot lysis, complement activation, and kinin generation are briefly reviewed. The interrelationship of the four systems is illustrated by the multiple functions of four key enzymes: Factor XIIa, kallikrein, plasmin, and C1 esterase. The pivotal role of Factor XIIa in establishing this connection is elucidated.
Is the trimodality of Hb leslie (α2β2131Gln → 0) in heterozygotes the result of a variable number of active α‐chain genes? Evidence for posttranslational control of hemoglobin synthesis
Authors: Felice A. , Abraham E. C. , Miller A. , Stallings M. , Huisman T. H. J.
Published: February 2007

Whether the trimodality in the relative concentration of the hemoglobin variant Hb Leslie in heterozygotes (Huisman, Hemoglobin 1: 349–382, 1977) is due to a polymorphism of the α‐chain structural genes was investigated by conventional incubation of reticulocytes with 14C‐leucine. In addition, an aliquot from each of the incubations was incubated under the same conditions but without isotope. Three Hb Leslie heterozygotes with presumably four, three (heterozygous α‐thalassemia‐2), and two (homozygous α‐thalassemia‐2) active α‐chain genes and with 33%, 22%, and 11% Hb Leslie respectively, and one patient with the Hb Leslie β0‐thalassemia condition with more than 85% Hb Leslie were studied. The data indicate that βLeslie chains have a lower affinity for α chains than βA chains. A concomitant α‐chain deficiency results in a reduced incorporation of βLeslie chains into the tetrameric Hb Leslie molecules, while the quantity of Hb Leslie produced correlates with the degree of α‐chain deficiency. Excess of βLeslie chains is preferentially degraded.
Hodgkin disease and red cell aplasia
Authors: Morgan Elaine , Pang Kin Man , Goldwasser E.
Published: February 2007

A teenage boy with mixed‐cellularity Hodgkin disease presented with severe anemia secondary to pure red cell aplasia of marrow without evidence of lymphomatous infiltration or hemolysis. In vitro studies of the patient's serum demonstrated an inhibitor of erythropoietin activity which appeared to be an IgG but which did not directly bind erythropoietin. The patient's anemia resolved and the inhibitor disappeared following chemotherapy for Hodgkin disease. Presumably, the inhibitor was directed at a very early stage of red blood cell production. This phenomenon may be related to other autoimmune manifestations occasionally seen in patients with lymphomas. The case is presented to bring attention to the unusual occurrence of red cell aplasia in Hodgkin disease. Several hypotheses concerning significance and etiology of the anemia are detailed.
Four new electrophoretically slow‐moving glucose 6‐phosphate dehydrogenase variants associated with congenital nonspherocytic hemolytic anemia found in Japan: Gd(‐) Kurume, Gd(‐) Fukushima, Gd(‐) Yamaguchi and Gd(‐) Wakayama
Authors: Miwa Shiro , Fujii Hisaichi , Nakatsuji Tadako , Ishida Yoji , Oda Etsuko , Sasai Shizuyo , Hiraoka Kozo , Kaneto Akira , Motokawa Masakazu , Ariga Yukio , Fukuchi Soitsu , Kashii Hiroomi , Kodama Teisuke
Published: February 2007

Four new glucose 6‐phosphate dehydrogenase (G6PD) variants which had electrophoretically slow‐moving characteristics associated with congenital nonspherocytic hemolytic anemia were discovered in Japan. Gd(‐) Kurume was found in a 17‐year‐old male whose red cells contained only 0.8% of normal enzyme activity. Gd(‐) Kurume had a normal Km G6P, normal Km NADP, low Ki NADPH, normal utilization of 2‐deoxy‐G6P and deamino‐NADP, very low heat stability and a biphasic pH curve. The hemolytic anemia was mild. Gd(‐) Fukushima was characterized from a 33‐year‐old male and had 2.8% of normal enzyme activity, normal Km G6P, normal Km NADP, low Ki NADPH, normal utilization of 2‐dcoxy‐G6P, low utilization of deamino‐NADP, low heat stability and a normal pH curve. The hemolytic anemia was mild. Gd(‐) Yamaguchi was characterized from an 8‐year‐old boy and had 3.5% of normal enzyme.
Effects of triiodothyronine on the anemia of chronic renal failure
Authors: Ferrer José , García Rafael , Rubio Lírimo , Rodríguez‐Itube Bernardo , Diez‐Ewald María
Published: February 2007

The present study was done in order to determine whether treatment with triodothyronine (T3) would improve the anemia of chronic renal insufficiency.

Four patients with stable renal failure and anemia were treated with 75 μg/day of T3 for a period of four weeks. The patients were not in chronic dialysis, had normochromic normocytic anemia and hypocellular bone marrow, and showed no evidence of external blood loss during the study. They had received no iron, folic acid, or androgenic steroids for at lcast six months prior to the study.

The administered dose of T3 was adequate to depress the serum levels of thyroid‐stimulating hormone (TSH); however, there was no detectable improvement in the levels of hemoglobin, hematocrit, bone marrow cellularity, serum and erythrocyte folate dcterminations, serum iron (Fc), 59Fe halflife, plasma iron turnover rate, percentage Fe incorporated into red blood cells, or in the ratio of surface radioactive counting over bone marrow/liver and spleen.

It is concluded that the experimental observations concerning direct bone marrow stimulation by T3 in anephric rats are probably not clinically applicable for the treatment of the anemia associated with uremia.
Decreased ribosomal RNA content and in vitro RNA synthesis in purified bone marrow erythroblasts of patients with idiopathic ineffective erythropoiesis and diguglielmo disease
Authors: Lourenço GraçA , Embury Stephen , Schrier Stanley L , Kedes Laurence H.
Published: February 2007

Ribsomal RNA content and in vitro3H‐uridine and3H‐thymidine incorporation were examined in purified marrow erythroblasts of patients with idiopathic ineffective eryth‐ ropoiesis (HE) and DiGuglielmo disease (DD) and compared with cells from normal marrows. Whereas H‐thymidine incorporation rates were normal in all patients,3H‐uridine incorporation was 42%‐75% of normal in cells from patients examined. Ribosomal RNA content was measured by spectrophotometric scanning of RNA electrophoresed on polyacrylamide gels and corrections made for contamination of the erythroblast preparations with ribosome bearing reticulocytes. In cells from every patient examined RNA content was decreased to 60‐76% of normal. Uridine incorporation and rRNA content of patients with β thalassemia minor and megaloblastic anemia were normal, suggesting that the defects observed in HE and DD were not due to ineffective erythropoiesis per se.

Since erythroblast ribosomes may be rate limiting in protein synthesis, we postulate that even a minor decrease in ribosome content might engender the ubiquitous abnormalities reported in erythroid cells in both HE and DD.
Activity of the Epipodophyllotoxin VP‐16 in the Treatment of Combination Chemotherapy‐Resistant Non‐Hodgkin Lymphoma
Authors: Bender Richard A. , Anderson Tom , Fisher Richard I. , Young Robert C.
Published: February 2007

Twenty patients with several histologic subtypes of non‐Hodgkin lymphoma who had become resistant to combination chemotherapy were treated with a five‐day course of the epipodophyllotoxin VP‐16. Of 19 evaluable patients, 8 (42%) responded to treatment with 1 complete response and 7 partial responses. The median duration of response was 5.5 months. Seven of the responders had a diffuse lymphoma and 1 had a nodular lymphoma. Of the responders who had diffuse histiocytic lymphoma (DHL), diffuse mixed lymphoma (DML), and diffuse undifferentiated lymphoma (DUL)–the more aggressive histologies in the Rappaport classification–6 of 13 (46%) evaluable patients responded to therapy. Responses were seen in node‐dominant, skin‐dominant, and marrow‐dominant disease. Toxicity was mainly hematopoietic, 53% of patients experiencing leukopenia (<2, 000 cells per cu mm) and 68% of patients experiencing thrombocytopenia (<100, 000 platelets per cu mm). There were two deaths attributable to profound leukopenia with sepsis. The activity of VP‐16 in patients who have previously been extensively treated with multiple drugs including vincristine supports its activity in the lymphomas and suggests its lack of cross‐resistance with vincristine. The inclusion of VP‐16 in primary treatment protocols in the diffuse lymphomas should be considered.
Inhibition of adriamycin‐induced human platelet lipid peroxidation by vitamin E
Authors: Stuart Marie J. , Dealarcon Pedro A. , Barvinchak Mary K.
Published: February 2007

Adriamycin® is an important cancer chemotherapeutic agent whose clinical use is compromised by potentially lethal cardiotoxicity. In the mouse, cardiotoxicity is related to the peroxidation of cardiac lipids. Both phenomena, however, can be reduced by pretreatment of the animal with vitamin E. Using the platelet as our model we have demonstrated that Adriamycin induces lipid peroxidation of human platelets in a dose‐dependent manner. Platelet malonyldialdehyde (MDA) production was used as an indicator of lipid peroxidation. Adriamycin at 5, 10, 50, and 100 μg/ml produced 1.40 ± 0.2 (1 SD), 2.23 ± 0.41, 4.23 ± 0.4, and 6.13 ± 0.43 nmoies MDA per 109 platelets, respectively. Vitamin E both in vitro and in vivo inhibited this lipid peroxidation. In vitro, vitamin E at concentrations of 0.01, 0.05, and 0.1 mg/ml inhibited platelet MDA formation by 14 ± 2, 29 ± 5, and 38 ± 6%, respectively. In six controls who ingested 1,600 units vitamin E daily for two weeks, platelet MDA formation induced by N‐ethyl maleimide, thrombin, and Adriamycin was decreased by 11‐20%. In similar studies, the ingestion of 10 grains acelyl salicylic acid (ASA) also inhibited platelet lipid peroxidation induced by these same agents. ASA and vitamin E were not additive in their inhibition of MDA formation induced by N‐ethyl maleimide or thrombin. They were additive, however, in their inhibition of Adriamycin‐induced lipid peroxidation, which suggests that the effect of vitamin E on Adriamycin‐induced platelet lipid peroxidation is not due to inhibition of platelet cyclooxygenase. In the light of these observations on the inhibitory effect of vitamin E on lipid peroxidation in human platelets, further studies appear warranted on the clinical effects of E in inhibiting cardiac lipid peroxidation and concomitant cardiotoxicity in humans on Adriamycin therapy.
Potentiation of vincristine cytotoxicity by hormones: Corticosteroids, androgens, estrogens and progestins
Authors: Rosner Fred , Hirshaut Yashar , Grünwald Hans W. , Deutsch Stanley
Published: February 2007

Using an in vitro system to evaluate the simultaneous use of two drugs, we previously have confirmed the synergism of vincristine and prednisolone cytotoxicity against lymphoid cells. Experiments were now carried out to determine whether other steroid hormones can be substituted for prednisolone. Partial or complete potentiation of vincristine cytotoxicity comparable to that achieved by the addition of prednisolone was observed when the latter drug was replaced by a variety of mineralocorticoids (aldosterone, desoxycorticosterone and fludrocortisone), glucocorticoids (hydrocortisone, dexamethasone), androgens (testosterone, methyltestosterone, androsterone, dehydroepiandrosterone, etiocholanolone), estrogens (estrone, 17‐βestradiol) and progestins (progesterone, pregnanediol). No potentiation of cytotoxicity was observed when nonsteroidal hormones (thyroxin, ACTH) were added to vincristine. It is concluded that a wide variety of compounds with the basic perhydrocyclopentano‐phenanthrene nucleus of the steroid molecule are capable of enhancing the cytotoxicity achieved with vincristine.
Recent developments in understanding the pathogenesis of aplastic anemia
Authors: Fitchen John H. , Cline Martin J.
Published: February 2007

Bone marrow failure in aplastic anemia (AA) could result from abnormalities of hematopoietic stem cells, abnormal control of hematopoiesis, or abnormalities of the hematopoietic environment. Bone marrow transplantation, in vitro marrow culture techniques, and studies in animal models of marrow failure have provided insights on the possible pathogenetic mechanisms underlying AA. Studies in man and in murine models suggest that most often AA results from injuries to hematopoietic stem cells. Despite the intriguing report of abnormal regulatory cells in congenitally anemic mice, instances of marrow failure due to defective humoral or cellular control of hematopoiesis have not been identified in man. In vitro studies employing allogeneic marrow targets have suggested that immune suppression of hematopoiesis may occasionally mediate AA in man. Marrow failure due to abnormalities of the hematopoietic microenvironment has been suggested by experience with bone marrow transplantation, but no direct study of this possibility has been reported. Based on available evidence, it seems likely that AA will prove to be many diseases that share common clinical and morphologic features.
Sickle cell anemia as a syndrome: A review of diagnostic features
Authors: Huisman Titus H. J.
Published: February 2007

Sickle cell (SS) disease is a complex of various genetic conditions. In some, homozygosity for the βS gene may be present alone or in combination with the heterozygous or homozygous α‐thalassemia‐2 condition. Such combinations might ameliorate the clinical and hematological condition of the patient. The same may be true for the high levels of Hb F and F‐cells observed in many Hb S homozygotes. However, the chemical heterogeneity of Hb F appears not to be related to the clinical status of the Hb S homozygote. Combinations of a Hb S heterozygosity with a heterozygosity for a Hb D‐type of variant, for either one of two types of β‐thalassemia, two types of δβ‐thalassemia, and five types of HPFH are discussed, and data are compared with those obtained for Hb S homozygotes. The use of advanced laboratory procedures and family studies is often necessary for an accurate diagnosis.
Effects of thrombopoietin and erythropoietin on platelet production in rebound‐thrombocytotic and normal mice
Authors: McDonald T. P. , Clift Rose
Published: February 2007

The effects of thrombopoietin‐rich (TSF‐rich) kidney cell culture medium and partially purified preparations of human urinary and step I sheep plasma erythropoietin (Ep) on platelet production in mice were determined. After TSF and Ep preparations had been injected into mice in rebound thrombocytosis and into normal mice, the rate of incorporation of Na2 35SO4 into platelets was measured as an index of platelet production. TSF injections caused significant increases in platelet production of all the mice; however, greater effects were observed in rebound‐thrombocytotic mice than in normal mice. In rebound‐thrombocytotic mice, low dosages of Ep (0.25–1.0 units per mouse) significantly depressed percentage 35S incorporation into platelets. The same low dosage of Ep did not alter platelet production rates in normal mice, but large doses (2.5–5.0 units per mouse) stimulated 35S incorporation into platelets. Thus, these results show that Ep caused different responses in rebound‐thrombocytotic and normal mice. Endotoxin, injected in dosages previously shown to be present in Ep, gave responses similar to that of the low dosages of Ep, ie, depressed thrombocytopoiesis in rebound‐thrombocytotic mice but had no effect in normal mice. When two foreign proteins were injected in doses similar to the previously tested Ep protein content, platelet production was not stimulated. We conclude, therefore, that the thrombocytopoietic effects of Ep cannot be due to contamination with known humoral factors or foreign proteins.
Inhibition by antimicrotubular agents of the procoagulant activity generated by the blood monocytes: A biochemical and morphological study
Authors: de Prost Dominique , Cramer Elisabeth , Hakim Jacques
Published: February 2007

During in vitro incubation, human blood leukocytes triggered by various stimuli, generate and release procoagulant activity (PCA), which was identified as tissue factor‐like activity. The cell responsible for this production is the monocyte. Monocytes, when incubated in aseptic conditions generate and release PCA in the incubation medium, after a lag period of 1–2 hours. Most of the activity (95%) remains cell bound while only 5% are released. In order to ascertain whether microtubules (MT) act as an intermediate in the generation and/or the release of PCA, monocytes were incubated with antimicrotubular agents ie, colchicine or vinblastine. Both drugs inhibited PCA generation and release.

Colchicine added after two hours of incubation was inhibitor after a lag period of one hour as expected by its delayed effectiveness on MT. The inhibition was more effective on the generation than on the release of PCA. Ultrastructural studies showed that both drugs significantly (P < 0.01) disrupted microtubules while no modifications of the protein synthetizing apparatus or the lysosomes were observed. No accumulating material was seen inside the cells.

These results suggest that colchicine or vinblastine act by their disrupting activity on MT, as inhibitors of PCA Generation by the monocytes. The decrease in PCA‐release would thus be secondary to a deficient generation of the activity. The absence of morphological modifications of the protein synthetizing apparatus suggest that antimicrotubular agents inhibit PCA synthesis by monocytes through the formation or transmission of the stimuli and not directly on the synthetizing sites.
Quantitative evaluation of antibody‐dependent lymphocyte‐mediated lysis of human red cells
Authors: Kurlander Roger J. , Rosse Wendell F. , Ferreira Euripides
Published: February 2007

The ability of lymphocytes to lyse human red cells coated with anti‐D antibody was assessed by measuring 51Cr release from labeled red cells incubated with peripheral blood leukocyte suspensions from 12 normal donors. Mixed mononuclear cell suspensions (containing monocytes and lymphocytes) from all donors produced lysis of sensitized red cells. Treatment with carbonyl iron reduced monocyte concentration to less than 1.2% in all donors, as measured by morphologic criteria, esterase staining and ingestion of latex particles. Lysis of red cells following monocyte depletion was markedly reduced in 8 of the 12 donors. Despite depletion of monocytes, unchanged or increased lysis was noticed with the leukocytes of the remaining 4 donors. This lysis was due to lymphocytes, not to residual monocytes. If target red cells were treated with papain or trypsin prior to sensitization, marked lysis occurred with lymphocytes of all donors, including those which did not lyse unmodified red cells. Direct cytolysis of sensitized red cells during contact with small lymphocytes was recorded using microcinematography, which confirmed the role of lymphocytes in mediating lysis.

Lymphocyte‐mediated lysis of red cells increased with mounting levels of antibody sensitization regardless of prior treatment with papain. Papain increased antibody coating per red cell, yet lysis per molecule of antibody bound was also increased. Lysis was inhibited by IgG1 and IgG3 in the fluid phase but not by IgG2 or IgG4. At an equivalent level of antibody sensitization lysis was augmented by concurrent coating of the red cells with C3b, C3d and/or C4b, though these components could not produce lysis in the absence of antibody coating.
Three new variants of glucose‐6‐phosphate dehydrogenase associated with chronic nonspherocytic hemolytic anemia: G‐6‐PD Lincoln Park, G‐6‐PD arlington heights, and G‐6‐PD West Town
Authors: Honig George R. , Habacon Evelina , Vida Loyda N. , Matsumoto Florinda , Beutler Ernest
Published: February 2007

Glucose 6‐phosphate dehydrogenase (G‐6‐PD) deficiency was identified in three children who were evaluated because of chronic nonspherocytic hemolytic anemia. One child is of German extraction, another Puerto Rican, and the third Mexican. In each of the patients the hemolytic process was well compensated, but each had one or more episodes of anemia following exposure to an oxidant drug or with infections. The electrophoretic, functional, and kinetic properties of the mutant enzymes, derived both from the patients' erythrocytes and from cultured fibroblasts, allowed each to be distinguished from G‐6‐PD variants previously described.
Intensive leukapheresis in the management of cytopenias in patients with chronic lymphocytic leukaemia (CLL) and lymphocytic lymphoma
Authors: Cooper I. A. , Ding J. C. , Adams P. B. , Quinn M. A. , Brettell M.
Published: February 2007

The role of leukapheresis was explored in the management of anaemia and thrombocytopenia complicating the accumulation of lymphoid cells in patients with chronic lymphocytic leukaemia and lymphoma. The aim of this study was to determine the efficiency of this procedure in correcting these complicating features and to assess the length of response and the clinical well being of the patients. Twenty such patients with either chronic lymphocytic leukaemia or lymphocytic lymphoma were studied using a Continuous Flow Cell Separator (Aminco Celltrifuge). All had persistent significant anaemia and/or thrombocytopenia prior to the institution of leukapheresis. The procedure was carried out on alternate days until significant reduction in total circulating lymphoid cells had been achieved, an average of 2.9 × 1011 cells being removed on each occasion. Thirteen of the twenty patients showed a significant elevation of both haemoglobin and platelet levels concomitant with the reduction in lymphoid cells. A reduction in organomegaly was also observed. These patients were classified as “responders,” but the other patients failed to show correction of the haematologic parameters. This procedure permitted a number of responder patients to receive more specific treatment but in some it obviated the necessity for any further management for up to 12 months.

Surface marker studies were also carried out on the lymphocytes of these patients. The patients who showed the best response to leukapheresis had cells characteristic of those seen in chronic lymphocytic leukaemia. The reduction of cells (82%) was greater in those who responded to this treatment than in the non‐responder group (72%). The procedure was well tolerated by all patients and overall provided a long‐term control of disease which outweighed the initial cost incurred.
Bone lesions in primary amyloidosis
Authors: Khojasteh Ali , Arnold Lowry K. , Farhangi Mehdi
Published: February 2007

Amyloidosis primarily involving bone is described in a 59‐year‐old male patient. Well circumscribed lytic lesions of the skeleton raised the possibility of myelomatosis. The prolonged insidious course of the disease was uncomplicated by hypercalcemia, pathological fracture, or hematologic abnormalities. The clinical course, together with histological findings and strongly positive bone scan, were the distinguishing features. The osseous manifestation without plasma cell tumor appears to be a rare occurrence in amyloidosis.
Host‐tumor interactions: Basis for the anemia in rats bearing the hepatoma 7777
Authors: Lamar Carlos , Greene Anne S. , Greene William B.
Published: February 2007

A significant anemia develops in Buffalo rats bearing the Morris hepatoma 7777. By indiceal measurements the red blood cells (RBCs) appear to be microcytic and hypochromic. Ferrokinetic studies demonstrate a decreased uptake of iron in the bone marrow and an increased incorporation of iron in the spleens of the tumor‐bearing animals.

RBC survival studies indicate the presence of a hemolytic component which appears to contribute to the anemia. The RBCs from tumor‐bearing animals (T‐RBC) have a greatly increased fragility in sodium chloride solutions. Inspection of these T‐RBCs by electron microscopy demonstrates significant echinocytosis when they are compared to normal cells.

Electrophoretic separation of the hemoglobin from T‐RBCs shows a pattern different from normal cells and consistent with the pattern described for hemoglobin from spleen and bone marrow.

The findings are consistent with bone marrow inadequacy and an increased splenic erythropoiesis which is insufficient to maintain normal hematological values. The hypothesis is presented that the RBCs synthesized under these circumstances appear in the circulation with an “immature” hemoglobin pattern and are hemolyzed more readily. This process then contributes to the hemolytic component and development of the anemia.
Temperature dependent activation of the alternate complement pathway by an IgG cryoglobulin
Authors: Poskitt Thomas R. , Poskitt Paula K. F.
Published: February 2007

A patient with chronic membranoproliferative glomerulonephritis is presented whose serum contains a monoclonal IgG3 cryoglobulin. The presence of persistent hypocomplementemia suggested the possibility that the cryoglobulin, upon cold‐induced precipitation, was capable of activating the complement system. Because visible cryoprecipitation commenced in vitro at 30°C, the patient's serum and normal serum to which had been added the isolated cryoglobulin were repeatedly cooled to 30°C and rewarmed to 37°C. This reproduction of the in vivo counterpart of blood circulating through an extremity exposed to the cold resulted in activation of C3‐proactivator (properdin factor B), C3 cleavage, and a 78% reduction in total hemolytic complement. This study demonstrates that IgG is capable of activating complement via the alternate pathway and reveals a mechanism through which this can occur in vivo; namely, by means of temperature dependent polymerization. In addition, we postulate that episodic complement activation initiated by the cryoglobulin contributed to the development of glomerulonephritis in this patient.
Isolation and characterization of granulocyte lysosomal proteins and study of their effects on the clotting system
Authors: Herion John C. , Bucher John R. , Penniall Ralph , Walker Richard I. , Baker Mary , Roberts Harold R.
Published: February 2007

Lysosomes (granules) of rabbit PMN leukocytes were extracted with either HCl or H2SO4, and the extracts were chromatographed over Sephadex to separate protein constituents. Some of the low molecular weight cationic proteins homogeneous on SDS PAGE (8% and 12.5% gels) were characterized by electrophoretic mobility in acid gels and by amino acid analysis. A 3,700 dalton polypeptide, rich in arginine and cysteine, prolonged the partial thromboplastin time of normal plasma. In low concentration, this protein shortened the clotting time of pure fibrinogen by thrombin. In high concentration this lysosomal cationic protein precipitated fibrinogen from solution; no fibrinopeptides were released to suggest cleavage of fibrinogen. Fibrinolytic protease activity was detected in crude H2SO4 extracts but not in crude HCl extracts.

Two separate plasminogen activators, differing from kallikrein or prekallikrein, were isolated from the H2SO4 lysosomal extract and were partially characterized; neither exhibited proteolytic activity on fibrinogen free of plasminogen.
The chromosomes and causation of human cancer and leukemia: XXXVIII. Cytogenetic experience in Ph1‐negative chronic myelocytic leukemia (CML)
Authors: Kohno Sei‐Ichi , Abe Syuiti , Sandberg Avery A.
Published: February 2007

Among 300 patients with chronic myelocytic leukemia (CML) followed at our institute during the last ten years, 36 (12%) were thought to have Ph1‐negative CML. In eight of these patients, chromosomal abnormalities were found in the leukemic cells; in four, the karyotypic abnormalities were established with banding techniques. The data of the present study and a review of the literature regarding chromosomal changes in Ph1‐negative CML indicate that: 1) no characteristic or consistent karyotypic change is present in Ph1‐negative CML and that diploidy is more common in this than any other leukemia; 2) the most common changes involve group C chromosomes (particularly +8); and 3) a missing Y is less common in Ph1‐negative CML than in its Ph1‐positive counterpart. The karyotypic changes in Ph1‐negative CML resemble more those encountered in Ph1‐positive CML than in acute myeloblastic leukemia (AML). The much shorter survival of the Ph1‐negative CML patients vs that of the Ph1‐positive group was again substantiated, and some of the previously reported clinical and laboratory findings unique to Ph1‐negative CML were confirmed. On the basis of the cytogenetic findings it is concluded that Ph1‐negative CML appears to be an entity unto itself.
Effect of zinc on hyperammonemia in sickle cell anemia subjects
Authors: Prasad Ananda S. , Rabbani Parviz , Warth James A.
Published: February 2007

An increase in plasma ammonia level in human volunteers on restricted zinc intake, and in zinc‐deficient rats, has recently been reported. Inasmuch as zinc deficiency has been observed in sickle cell anemia patients, we measured plasma ammonia levels in such subjects. In this report we document hyperammonemia in sickle cell anemia patients that was corrected with zinc therapy.