bluuebunny/crossref_metadata_2025 huggingface dataset:
Acquired von Willebrand disease and storage pool disease in chronic myelocytic leukemia
Authors: Mohri Hiroshi
Published: February 2007

Platelet function was evaluated in 20 patients with chronic myelocytic leukemia (CML), all Ph positive. Seven showed abnormal epinephrine‐induced aggregation, while four had impaired both ADP‐ and collagen‐induced aggregation. The platelets of all patients aggregated with arachidonic acid, thus ruling out cyclooxygenase or lipoxygenase deficiency. The intracellular concentrations of ATP and ADP were significantly below normal, and the ratio of ATP/ADP was greater than normal in all 12 patients. ATP released from platelets by Lumi‐aggregometer was reduced. In four patients with abnormal ristocetin‐induced aggregation, vWF:Ag, RCoF, and FVIII:C were all reduced. No significant inactivation of factor VIII was induced in normal plasma by incubation with patient's plasma. The crossed immunoelectrophoretic analysis revealed that vWF:Ag in these patients was mainly composed of more anodic component as compared with that of normal plasma. The ratio of vWF:Ag/RCoF was significantly greater than normal. A marked increase of factor VIII and a rapid return of vWF:Ag and RCoF to the baseline after the 1‐deamino‐8‐arginine vasopressin (DDAVP) infusion were observed. Transient increase in vWF:Ag after the infusion of DDAVP appeared with less anodic forms and in the same relative proportion as that in normal plasma. The present study shows that in some patients with CML storage pool disease occurs with acquired von Willebrand disease.
A new case of high‐molecular‐weight kininogen inherited deficiency
Authors: Lefrère Jean‐Jacques , Horellou Marie‐Hélène , Gozin Danièle , Conard Jacqueline , Muller Jean‐Yves , Clark Michael , Soulier Jean‐Pierre , Samama Meyer
Published: February 2007

A preoperative hemostasis study discovered a prolonged activated partial thrombo‐plastin time in a 23‐year‐old Portuguese Caucasian woman without personal or past family history of hemorrhage or thrombosis. This was corrected by pooled plasma that excluded circulating anticoagulant. Activated partial thromboplastin time was prolonged whatever the activator, particularly ellagic acid, and was not corrected by prolonged kaolin incubation. Levels of factors VIII and XII were normal; factor XI and prekallikrein levels were either moderately low or normal according to activators and defective reagents used. High‐molecular‐weight kininogen (HMWK) level assessed by coagulation and immunological method was virtually nil. Fibrinolysis activity was normal before and after veinous occlusion. The programmed operation was performed without any particular preparation and no complication arose. Family investigation found heterozygous HMWK deficiency in the proposita's father and three of her siblings.
Studies of the effects of trimethoprim and sulfamethoxazole on human granulopoiesis
Authors: Bjornson Barbara H. , McLntyre Angus P. , Harvey John M. , Tauber Alfred I.
Published: February 2007

Trimethoprim and sulfamethoxazole (Bactrim r) is a widely used antibiotic combination effective against a broad spectrum of microbial organisms. There are reports of neutropenia developing during even brief periods of oral therapy, particularly in individuals with either folate deficiency or increased folate requirements. We have investigated the effects of these drugs on circulating granulocyte precursors (CFU‐C) from normal donors and the mechanism of inhibition on granulopoiesis using an in vitro CFU‐C assay. In 12 healthy adults, the number of circulating granulocytes and granulocyte progenitors was not significantly altered by a 5‐day course of therapy. However, in experiments that simulated the in vivo condition of folate deficiency (folate‐free cultures were prepared with cells harvested from normal donors), trimethoprim (8 μg/ml) resulted in a 47% decrease in the total number of colonies; this inhibitory effect was prevented when 100 ng of folinic acid was also added to the culture. Sulfamethoxazole (40 μg/ml) had no discernible effect on granulopoiesis. The combination of 8 μg/ml of trimethoprim and 40 μg/ml of sulfamethoxazole resulted in a 52% decrease in the number of colonies generated and this inhibition was again prevented by folinic acid. Our results suggest that the neutropenia occasionally observed in patients treated with trimethoprim‐sulfamethoxazole is due to the inhibitory effects on granulopoiesis by trimethoprim, namely its antifolate action, which is reversed by folinic acid. Based on these studies, in patients with either folate deficiency or increased folate requirements, trimethoprim‐sulfamethoxazole should be used with caution.
Erythrocyte Rh antigens increase with red cell age
Authors: Ballas Samir K. , Flynn John C. , Pauline Lucy A. , Murphy Darci L.
Published: February 2007

Certain blood group antigens may play a role in the removal of senescent red cells from the circulation. In order to elucidate this hypothesis, we have investigated the effect of red cell aging on Rh blood group antigens. Red cells from volunteer donors were separated into subpopulations of uniformly defined densities on discontinuous Stractan density gradients. The number of the five major Rh antigen sites of each fraction was determined both by enzyme‐linked immunosorbent assay (ELISA) and by hemagglutination‐scoring technique. All Rh antigens tested increased with cell age (p < 0.01). The data indicate that there is a positive correlation between red cell age and the Rh blood group antigen site number.
G‐6‐PD Walter Reed: Possible insight into “structural” NADP in G‐6‐PD
Authors: Beutler Ernest , Hartman Kip , Gelbart Terri , Forman Linda
Published: February 2007

A new Gd‐PD variant, Gd‐PD Walter Reed, causing hereditary nonspherocytic hemolytic anemia is characterized. This variant is unusual in that its stability requires the presence of high concentrations of NADP, while its Km for NADP is normal. This finding is consistent with the suggestion that Gd‐PD has two separate binding sites, a high affinity “structural” site and a lower affinity catalytic site. The mutation in G‐6‐PD Walter Reed, like that of the previously described variant, G‐6‐PD Torrance, may be due to a mutation of the “structural” site for NADP.
Acute renal infarction in sickle cell disease
Authors: Granfortuna James , Zamkoff Kenneth , Urrutia Enrique
Published: February 2007

End organ failure in sickle cell disease has classically been attributed to changes in the microvasculature. A case is reported in which sudden and complete loss of blood flow to the left kidney occurred during a painful crisis in a woman with homozygous SS disease. The findings are most consistent with occlusion of the renal artery.
Serum markers for type IV collagen and type III procollagen in the myelofibrosis‐osteomyelosclerosis syndrome and other chronic myeloproliferative disorders
Authors: Hasselbalch H. , Junker P. , Lisse I. , Bentsen K. D. , Risteli L. , Risteli J.
Published: February 2007

Myelofibrosis is characterized by excessive deposition of interstitial and basement membrane collagens in the bone marrow. In this study, specific radioimmunoassays for the aminoterminal propeptide of type III procollagen and for the 7S collagen domain of type IV (basement membrane) collagen were used to determine how this accumulation is reflected in serum.

Of the 41 patients with chronic myeloproliferative disorders studied, the highest levels of both parameters were found in idiopathic myelofibrosis and in chronic myelogenous leukaemia associated with bone marrow fibrosis. Increasing degrees of bone marrow fibrosis were accompanied by increasing serum concentrations of both markers, except for osteomyelosclerosis, where notably low values were seen. Pathologically high values of one or both parameters were also found in a few patients with polycythaemia Vera or a transitional myeloproliferative disorder.

The antigens related to type III procollagen and type IV collagen correlated significantly with each other and with the leucocyte count. These parameters should provide noninvasive means for following the accumulation of interstitial and basement membrane collagens in the bone marrow.
Excessive fibrinolysis in suspected amyloidosis: Demonstration of plasmin‐α2‐plasmin inhibitor complex and von Willebrand factor fragment in plasma
Authors: Takahashi Hoyu , Koike Tadashi , Yoshida Nobuhiko , Kitahara Osamu , Hanano Masaharu , Shibata Akira , Aoki Nobuo
Published: February 2007

We performed a hemostatic evaluation in detail in a patient with suspected amyloidosis who was suffering from several bleeding episodes. He had a shortened euglobulin clot lysis time, decreased alpha 2‐plasmin inhibitor (α2‐PI), decreased plasminogen, elevated tissue‐type plasminogen activator (t‐PA), elevated plasmin‐α2‐PI complex, and decreased ratio of ristocetin cofactor to von Willebrand factor (vWF) antigen. Fibrinogen and fibrin/fibrinogen degradation products levels fluctuated, with abnormal values on several occasions. On crossed immunoelectrophoresis, plasmin‐α2‐PI complex and vWF fragment were demonstrated in the patient plasma. These abnormal findings and bleeding symptoms improved following the administration of tranexamic acid. Discontinuation of tranexamic acid resulted in deterioration of these parameters. These observations indicate that pathologic fibrinolysis (continuous intravascular plasmin generation) characterized by the consumption of α2‐PI and plasminogen, formation of plasmin‐α2‐PI complex, and fragmentation of vWF contributed to the bleeding in this patient. It is important to recognize excessive fibrinolysis as the underlying cause of bleeding in these patients, since specific treatment with antifibrinolytic agents is effective in controlling the bleeding.
In vitro effects of gammaglobulin (IgG) on human monocyte Fc receptor function. I. Effect on monocyte membrane‐associated IgG and Fc receptor‐dependent binding of antibody‐coated platelets
Authors: Saleh Mansoor N. , Court Wayne S. , Lobuglio Albert F.
Published: February 2007

Intravenous immunoglobulin (IV IgG) has been reported to be clinically beneficial for the treatment of immune thrombocytopenic purpura (ITP). The mechanism of effect still remains unknown. We examined the in vitro effects of two commercially available IV IgG preparations. Exposure of normal monocytes to IgG in vitro produced a significant increase in monocyte‐bound IgG. Prior treatment of the commercial IgG preparations by filtration through a 0.2‐μm Millipore filter or ultracentrifugation caused a dramatic decrease in IgG bound to the monocyte surface, indicating that IgG aggregates were responsible for this effect. Exposure of monocytes to IgG levels as high as 150 mg (Sandoglobulin) and 400 mg (Gamimune) did not result in a statistically significant inhibition of monocyte‐platelet interaction as examined by a morphologic rosetting assay. Thus, despite the ability of IV IgG preparations to cause substantial increments in monocyte surface IgG, impairment of Fc receptormediated monocyte binding of antibody‐coated platelets was not observed.
Increased fibrinolytic activity in patients undergoing cardiopulmonary bypass operation
Authors: Kucuk Omer , Kwaan Hau C. , Frederickson James , Wade Leonard , Green David
Published: February 2007

The influence of cardiopulmonary bypass on fibrinolytic activity was assessed by a sensitive clot lysis assay in eight patients undergoing coronary artery bypass operations. Fibrinolytic activity increased immediately after cardíopulmonary bypass was begun and remained elevated throughout the period of extracorporeal circulation. At the conclusion of the operative procedure, fibrinolytic activity returned to the normal range in all patients, and no subject had postoperative bleeding.
Kinetic analysis in single, intact cells by microspectrophotometry: Evidence for two populations of erythrocytes in an individual heterozygous for glucose‐6‐phosphate dehydrogenase deficiency
Authors: Ashmun Richard A. , Hultquist Donald E. , Schultz Jerome S.
Published: February 2007

A microspectrophotometric technique was used to measure the kinetics of methemoglobin reduction in intact, unaltered human erythrocytes. Reduction was catalyzed by endogenous NADPH‐methemoglobin reductase in the presence of Nile Blue. The technique was applied to the study of erythrocytes from a female donor with decreased glucose‐6‐phosphate dehydrogenase (G‐6‐PD) activity. The individual was shown to be heterozygous for deficiency of G‐6‐PD. The kinetic study revealed two distinct populations of erythrocytes that were nearly equal in number. One cell population showed reduction rates between 0 and 25% of normal, whereas the second cell population displayed rates within the range seen for normal cells. Single‐cell indices of cell size, cell hemoglobin content, and ratio of cell hemoglobin to cell size did not correlate with single‐cell reduction rates and were not significantly different between the two populations. These results provide quantitative support for the X‐inactivation hypothesis in G‐6‐PD deficiency.
Pure red cell aplasia: Response to therapy with anti‐thymocyte globulin
Authors: Abkowitz Janis L. , Powell Jerry S. , Nakamura Jeffrey M. , Kadin Marshall E. , Adamson John W.
Published: February 2007

Pure red cell aplasia (PRCA) results from the failure of erythrocyte differentiation and may respond to immunosuppressive therapies. We have treated nine patients with PRCA refractory to steroids and/or cyclophosphamide with anti‐thymocyte globulin (ATG). Six patients had normal numbers of erythroid bursts (from erythroid burstforming units) or erythroid colonies (from erythroid colony‐forming units) detectable in vitro, and all responded to therapy with ATG. In vitro studies suggested T‐cell inhibition of erythropoiesis in four of these six patients and humorally mediated erythroid suppression in one. In three individuals, virtually no erythroid progenitors were detected in marrow culture. None of these patients responded to ATG. Myelo‐fibrosis, 5q‐ chromosomal abnormality, or the subsequent development of thrombo‐cytopenia in these individuals suggested that PRCA resulted from an intrinsic stem cell disorder. Our studies demonstrate that ATG is effective therapy for PRCA, and it may be especially useful in children or other patients in whom alkylating agents are not appropriate. We also confirm that erythroid growth in marrow culture predicts those patients who will respond to ATG or other immunosuppressive therapies.
Echinocyte‐stomatocyte transformation and shape control of human red blood cells: Morphological aspects
Authors: Reinhart Walter H. , Chien Shu
Published: February 2007

Red cell morphology was studied after the induction of echinocytic transformation by metabolic depletion, Ca2+ loading, and salicylate and stomatocytic transformation with chlorpromazine. The results indicate that the red cell has an energy‐dependent shape control mechanism that allows it to counteract shape‐changing stimuli such as metabolic depletion. Albumin was found to induce stomatocytic transformation, whereas γ‐globulins induced echinocytic transformation. Loading of the red cell with calcium resulted in polymorphous membrane damages such as submembranous, “blister‐like” lesions, and membrane disintegration; the red cell age had no influence on this process. Conversely, the stomatocyte‐echinocyte transformation induced by chlorpromazine and salicylate was shifted towards echinocytes in density‐separated old red cells. Sphero‐stomatocytes were capable of echinocytic transformation with spicule formation within the red cell vacuoles, whereas sphero‐echinocytes were unable to undergo stomatocytic transformation without hemolysis. These observations may help to unravel the complexity of echinocyte‐stomatocyte transformation of red blood cells.
Clinical and molecular correlations in the sickle/β+‐thalassemia syndrome
Authors: Atweh George F. , Forget Bernard G.
Published: February 2007

Sickle/β thalassemia is a sickling disorder of varying severity which results from compound heterozygosity for sickle cell trait and β‐thalassemia trait. Clinical and genetic studies have shown an inverse correlation between the level of hemoglobin A and the severity of the disease. It has been suggested that the level of hemoglobin A may be a function of the severity of the β‐thalassemia defect. In this study, we use molecular biological techniques to test this hypothesis. We show that the interaction of the mildest of the β+‐thalassemia genes with the sickle gene results in a high level of hemoglobin A. However, the interaction in this case resulted in a severe sickling disorder in the absence of significant anemia. We hypothesize that a mild β+‐ thalassemia gene may have two opposite effects on the clinical course of sickle/β+ thalassemia: (1) A high level of hemoglobin A which probably confers a favorable antisickling effect and (2) decreased hemolysis leading to increased numbers of total circulating red cells, thereby increasing the blood viscosity and the propensity for sickling. The inheritance of heterozygous α thalassemia 2 in conjunction with the mild β+‐thalassemia gene and sickle gene in this patient may have further enhanced the latter effect and resulted in a severe sickling disorder.
Leu 7+, Leu 11a− acute T‐lymphoblastic leukemia having low K cell activity and NO NK cell activity
Authors: Falcäo Roberto P. , Ismael Sebastiäo J.
Published: February 2007

The phenotypic and functional features of the leukemic blasts from a child with Tacute lymphoblastic leukemia (T‐ALL) were studied. The leukemic cells lacked the usual markers of T‐cell lineage (T3−, T11−, E‐sheep−) although they displayed some T‐lymphocyte markers (T6+, T8+, T9+, T10+) and were Tγ−. Furthermore, these cells had a strong reaction with anti‐Leu 7 but were negative to anti‐leu 11a antibody and exhibited low K cell activity, no NK activity, and showed virtually no response to PHA. These leukemic cells probably represented the leukemic counterpart of the Leu 7+, Leu 11a− subset that has been demonstrated in the peripheral blood of normal individuals.
Normal pregnancy in a patient with a postpartum factor VIII inhibitor
Authors: Vicente V. , Alberca I. , Gonzalez R. , Alegre A.
Published: February 2007

A patient who had developed a VIII:C IgG‐Kappa antibody after her first delivery became pregnant for a second time. At that time the titer of the inhibitor had increased fourfold, remaining at high levels throughout the rest of the pregnancy. The neonate exhibited an inhibitor with characteristics identical to that of the mother which could not be detected 3 months after birth. No hemorrhagic complications in either of the subjects were observed.
Restoration of impaired natural killer cell activity of B‐chronic lymphocytic leukemia patients by recombinant interleukin‐2
Authors: Kay Neil E. , Zarling Joyce
Published: February 2007

Natural killer (NK) function in the majority of B‐cell chronic lymphocytic leukemia patients is markedly deficient. This study was undertaken to determine if the biological response modifier interleukin‐2 (IL‐2), which is a potent augmenter of normal individuals' NK activity, could augment the low NK activity in these patients. Peripheral blood lymphocytes (PBL), depleted of B‐cells, from most B‐CLL patients exhibited low natural killer activity against NK‐sensitive K562 cells and against herpes simplex virus (HSV)‐infected lymphoblastoid cell lines (LCL). Incubation of patients' B‐cell‐depleted PBL with recombinant IL‐2 resulted in augmentation of their NK activity against both K562 cells and HSV‐infected cells. Furthermore, whereas large granular lymphocytes (LGL) isolated from CLL patients are deficient in cytoplasmic granules, which are thought to play a role in NK‐cell‐mediated lysis, treatment of patients' LGL resulted in increased granulation by 4 hr after treatment with IL‐2 and showed a concomitant increase in lytic activity comparable to that of normal individuals.
Additional variant of type I von willebrand disease
Authors: Tavori S. , Tatarsky I.
Published: February 2007

We introduce a family with a von Willebrand subgroup that has not been described before. All of the eight subjects examined had normal levels of factor VIII coagulant activity (FVIII:C), a moderate reduction in the level of von Willebrand factor antigen (VWF:Ag), which resulted in a high FVIII: C/VWF: Ag ratio, and normal crossed immunoelectrophoresis, with normal multimeric pattern. The ristocetin cofactor in plasma and platelets was very low. Bleeding time was prolonged in two subjects without clearcut linkage to laboratory findings. In addition, an abnormality of platelet aggregation in response to ADP was observed: a decreased initial response was followed by marked disaggregation.
Prothrombin “Mexico city,” an asymptomatic autosomal dominant prothrombin variant
Authors: Valls‐de‐Ruiz Matilde , Rulz‐Arguelles Alejandro , Ruiz‐Arguelles Guillermo J. , Ambriz Raul
Published: February 2007

A functionally normal but structurally abnormal prothrombin variant was found in a Mexican family. Immunoisoelectricfocusing studies revealed that this variant has a more acidic isoelectric point (4.01) than normal prothrombin (4.29), but it proved to have a normal molecular weight as assessed by sodium‐dodecyl‐sulphate polyacrylamide gel electrophoresis. Two‐dimensional immunoelectrophoresis studies showed an abnormal cleavage of the prothrombin molecule by factor Xa and Echis carinatus venom as well, despite the fact that both yield functionally normal thrombin molecules. Finally, the ability of the molecule to bind calcium ions as well as its overall antigenic structure were investigated and found to be normal. These results taken together suggest a simple (substitution or translocation) mutation at the fragment 2 level. Since this prothrombin variant is different from others described previously, the name “Mexico City” is proposed to identify it.
Incidence of inhibitors in patients with severe and moderate hemophilia a treated with factor VIII concentrates
Authors: Schwarzinger Iise , Pabinger Ingrid , Korninger Christian , Haschke Ferdinand , Kundi Michael , Niessner Herwig , Lechner Klaus
Published: February 2007

Recent data published on the prevalence of inhibitors to factor VIII in hemophiliacs on treatment show great variations, with prevalence rates ranging from 3.6 to 14.2%. We have studied the cumulative risk of inhibitor development in a cohort of 62 patients with hemophilia A. All patients were born after 1960, were natives of the Vienna area, had a factor VIII activity of less than 5%, and were treated at least once. Using the method of Cutler and Ederer, the cumulative risk of inhibitor development was found to be 24% at the age of 25 years. Most inhibitors developed between the ages of 3 and 7 years. The current prevalence of F VIII inhibitors in the group of patients studied is 17.5%. It is concluded that prevalence data underestimate the true risk of inhibitor development.
Hematological aspect of Rh deficiency syndrome: A case report and a review of the literature
Authors: Nash R. , Shojania A. M.
Published: February 2007

The hematological aspects of the original case of Rhmod are reported. The subject, as in other reported cases, had a chronic hemolytic anemia characterized by stomatocytosis, reduced osmotic fragility, and abnormal autohemolysis correctable with the addition of glucose. The 51Cr red cell survival studies showed the spleen to be the preferential site of red cell destruction and splenectomy produced a dramatic improvement in red cell survival. The topic of Rh deficiency syndrome (Rhnull and Rhmod) is briefly reviewed with regard to the number of cases reported, to genetic aspects, to the hematological findings, and to the results of splenectomy.
Effectiveness of oral iron chelators assayed in the rat
Authors: Kim Byoung‐Kook , Huebers Helmut A. , Finch Clement A.
Published: February 2007

A 4‐hour in vivo test for iron chelator activity in the rat is described. The amount of radioiron in the gut and urine that results from chelator‐induced excretion of previously injected radioiron labelled ferritin is measured. Hepatocyte localization and desferrioxamine‐induced radioiron mobilization from in vitro tagged homologous ferritin is shown to be similar to that from in vivo tagged ferritin. Non‐homologous ferritin preparations labelled in vitro proved unsatisfactory. Radioiron mobilization by chelator occurred regardless of the iron status of the animal. Employing this measurement, the effectiveness of three iron chelators, pyridoxal isonicotinoyl hydrazone, the dimethyl ester of ethylene diamine‐N, N′‐dis (3‐hydroxyphenyl acetic acid), and the dimethyl ester N, N′‐di (3‐hydroxybenzyl) ethylene‐1, ethylene‐1, 2‐diamine‐N, N′‐diacetic acid, given orally was determined. All three chelators, when given in comparable dosage, induced iron execretion similar in amount to that observed with parenteral desferrioxamine. In addition, pyridoxal isonicotinoyl hydrazone administered in the diet over a period of 4 weeks was shown to reduce hepatic and splenic iron of normal animals by about one third, providing further validation of this method of evaluating chelator effectiveness.
Cyclosporin treatment for aplastic anemia: A case report demonstrating a second response to second exposure to cyclosporin
Authors: Bern Murray M. , Roberts Mark S. , Yoburn David
Published: February 2007

Cyclosporin has been used in the treatment of aplastic anemia, often in combination with other drugs, making it difficult to make a clear distinction between the effects of cyclosporin and those of other treatments. This report demonstrates a clear response of a patient with aplastic anemia to single drug cyclosporin therapy.
Thrombotic thrombocytopenic purpura: Treatment with plasmapheresis
Authors: Blitzer Jonathan B. , Granfortuna James M. , Gottlieb Arlan J. , Smith J. Robert , Theodorakis Michael E. , Zamkoff Kenneth W. , Landaw Stephen A. , Goldberg Jack , Scalzo Anthony J. , Lamberson Harold
Published: February 2007

Twenty‐one episodes of thrombotic thrombocytopenic purpura (TTP) were treated with plasmapheresis. Adjunctive agents included corticosteroids, aspirin, dipyridamole, and vincristine. There were 17 patients; 12 were female. The median age was 41 years. Most patients presented with neurologic symptoms. Thrombocytopenia was profound with a mean initial platelet count of 14,900/mm3. The mean hematocrit on presentation was 26.7% and the mean LDH 1300 IU/L. Eighteen episodes responded completely following plasmapheresis/plasma exchange (86%). Response was prompt, the initial rise in platelet count occurred after a mean of four exchanges, and complete response (a platelet count over 150,000/mm3) was obtained after a mean of nine exchanges. Four of the episodes treated were relapses that occurred in three patients. All responders are alive with a median duration of follow‐up of 20 months. The three patients who failed to respond have died. This report extends recent observations that the addition of plasmapheresis/plasma exchange to the therapy of TTP has significantly improved the outlook for patients with this disorder.
Clinical and laboratory changes induced by alpha interferon in chronic lymphocytic leukemia‐a pilot study
Authors: Talpaz M. , Rosenblum M. , Kurzrock R. , Reuben J. , Kantarjian H. , Gutterman J.
Published: February 2007

Ten chronic lymphocytic leukemia patients were treated with partially pure alpha interferon (IFN‐α) at doses ranging from 3‐9 × 106 units administered intramuscularly daily. Of these patients, three patients with disease stages 0, 1, and 3 (and prolymphocytic leukemia), respectively, responded with partial remissions lasting from 10 to 24+ months; four additional patients had minor responses. Among those responding, modulation of B cell chronic lymphocytic leukemia, surface immunoglobulins, and surface antigens were observed in four patients. These changes included a decline in the proportion of B cells bearing surface immunoglobulin without change in the number of the B cells. Likewise, a decline in the proportion of B cells bearing T‐1 antigen was observed in three patients. Increase in the percentage of T cells, primarily the T helper cells, was seen in two of the responding patients. Specific binding of α interferon was demonstrated prior to therapy in CLL cells of all patients. This binding declined rapidly following treatment with IFN α.

Induction of the enzyme 2′ 5′ oligoisoadenylate synthetase was examined in CLL patients prior to and during therapy with IFN‐α. Variable levels of the enzyme were induced in all patients on therapy; however, only minimal induction was observed in two of three patients failing therapy.
Anti‐platelet and Anti‐DNA IgM in waldenström macroglobulinemia and ITP
Authors: Vartlcovski L. , Pick A. I. , Schattner A. , Shoenfeld Y.
Published: February 2007

We describe a monoclonal IgM that was purified from the serum of a patient with Waldenstrom macroglobulinemia and thrombocytopenia. The binding and idiotypic characteristics of the patient's macroglobulin were similar to those of a human monoclonal IgM secreted by a hybridoma established from peripheal blood lymphocytes of a patient with systemic lupus erythematosus and immune thrombocytepenia.

In the absence of other causes for thrombocytopenia in this patient, our results suggest an autoimmune mechanism for destruction of platelets by the monoclonal IgM. This is the first report of a Waldenstrom macroglobulinemia with anti‐platelet activity of monoclonal IgM.

Although the study involves a single patient, the results suggest that there may be a common origin for autoantibodies in autoimmune diseases and monoclonal immunoglobulins having autoantibody activity in monoclonal gammopathies.
Hb Q‐Thailand‐Hb H disease in a chinese living in Geneva, Switzerland: Characterization of the variant and identification of the two α‐thalassemic chromosomes
Authors: Beris P. , Huber P. , Miescher P. A. , Wilson J. B. , Kutlar A. , Chen S. S. , Huisman T. H. J.
Published: February 2007

Data on a 24‐year‐old Chinese male with Hb Q‐Thailand‐Hb H disease are presented. The hemoglobin variant was characterized by fast microprocedures, mainly by reverse‐phase high‐performance liquid chromatography. Gene mapping analyses identified the α‐thalassemia‐2, which is associated with the α‐Q chain, as caused by a 4.2‐kb deletion involving the α2 globin gene, while the α‐thalassemia‐1 anomaly was the common Southeast Asian type in which part of the Ψζ, the Ψα, and the α2 and α1 globin genes are deleted.
Phenotypic changes associated with chemically induced differentiation of a hairy cell leukemia cell line
Authors: Hooper W. Craig , Barth Rolf F. , Minowada Jun
Published: February 2007

In vitro chemically induced differentiation of the JOK‐1 cell line, derived from a patient with hairy cell leukemia, has been studied. Non‐induced JOK‐1 cells expressed sIgM, B‐1, CALLA, Ia, and C3 receptors. Following exposure to 2% DMSO, or 100 ng/ml 12‐0‐tetradecanoyl‐phorbol‐13‐acetate (TPA), the cells underwent a phenotypic change from lymphoblastoid to monocytoid. In the presence of TPA, they became adherent and developed dendritic processes. Associated with these changes was a decrease in sIgM and CALLA and variable expression of C3 receptors. No monocyte/macrophage‐associated antigens were detected. These results suggest that the JOK‐1 cell line may have a limited ability to differentiate but is not mature enough to complete the differentiation process.
Immunological aspects of the anemia of rheumatoid arthritis
Authors: Sugimoto Masakuni , Wakabayashi Yoshihisa , Hirose Shun‐Ichi , Takaku Fumimaro
Published: February 2007

In order to investigate the cause of the anemia concomitant with rheumatoid arthritis (RA), we examined, using the erythroid colony assay of human bone marrow colonyforming units‐erythroid (CFU‐e) and burst‐forming units‐erythroid (BFU‐e), the effects of the patients' serum and peripheral blood T lymphocytes on the CFU‐e‐derived colonies.

The counts of erythroid colonies of RA patients were markedly lower than those of human control subjects [CFU‐e: control 152.9 ± 30.6 (n = 19), RA 51.1 ± 13.6 (n = 7), t = 7.66567, p < 0.01; BFU‐e: control 25.2 ± 5.9 (n = 5), RA 12.6 ± 2.6 (n = 7), t = 4.574, p < 0.01]. The serum from two out of seven RA patients slightly inhibited the formation of CFU‐e‐derived colonies of human control subjects (t = 2.31, 0.05 < p < 0.1); however, the serum from the other five RA patients did not significantly inhibit human control erythroid colony formation as compared with human control serum (t = 0.981, 0.3 < p < 0.4). On the other hand, peripheral blood T lymphocytes of the patients markedly inhibited the formation of CFU‐e‐derived colonies of the control subjects (t = 4.24, p > 0.01).

The above‐mentioned results suggest that the peripheral blood T lymphocytes of RA patients might play a role as one of the causes of the concomitant anemia of RA patients.
Immunoarchitecture of the bone marrow in neutropenia: Increased HNK‐1 + cells define a subset of neutropenic patients
Authors: Picker Louis J. , Kadin Marshall E. , Furst Annette , Robinson Stephen H.
Published: February 2007

An immunoperoxidase technique was used to examine the distribution of lymphocyte subsets in bone marrow biopsies of 15 patients with neutropenia and seven non‐neutropenic controls. The bone marrow of most patients and controls had similar distributions of immune effector cells characterized by a diffuse array of predominantly cytotoxic/suppressor T‐cells and occasional nodular aggregates of helper T‐cells. Cells displaying the natural killer cell marker HNK‐1 were sparse in controls and most neutropenic patients. However, marked increases in marrow HNK‐1 + cells were identified in four of the 15 patients. Three of these patients had diffuse HNK‐1 + infiltrates associated with increased Leu 4+ (OKT‐3 +) T‐cells while one had a nodular HNK‐1 + infiltrate associated with small B‐cell follicles. Each of these patients had clinical features similar to those described in the large granular lymphocyte (LGL) lymphocytosis (leukemia) syndrome, but only one of four demonstrated persistently increased numbers of LGLs in the peripheral blood. Thus, this study extends the association of neutropenia and increased numbers of cells with a T/NK phenotype to include patients whose bone marrow is the only demonstrable site of involvement. Since morphologic examination of the bone marrow could not identify the bone marrows with increased HNK‐1 + cells, immunulogic techniques are required to detect these cases.
Correction of the bleeding time in treated patients with severe von willebrand disease is not solely dependent on the normal multimeric structure of plasma von willebrand factor
Authors: Mannucci P. M. , Moia M. , Altieri D. , Rebulla P. , Monteagudo J. , Castillo R.
Published: February 2007

Even though it is generally held that cryoprecipitate and fraction I‐0 correct the prolonged bleeding time (BT) in patients with von Willebrand disease (VWD), perusal of reported data indicates that the correction is usually short‐lasting and often partial. We decided to do a controlled study of the relationship between the multimeric structure of von Willebrand factor (VWF) and the BT in five patients with severe (type III) VWD after infusion of three plasma concentrates (“wet” cryoprecipitate, lyophilized cryoprecipitate, and fraction I‐0) given in random order. The dosage of concentrates was tailored from in vitro measurements to achieve post‐infusion levels of ristocetin cofactor above the lower normal limit (50 U/dL) for at least 3 hours. The postinfusion BT became transiently normal in only two of five patients treated with wet cryoprecipitate, whereas it remained prolonged in all five patients treated with lyophilized cryoprecipitate or fraction I‐0. For all the concentrates, the proportion of large VWF multimers calculated by scanning the electrophoretic gels were the same as those for normal standard plasmas. An intact multimeric structure was recovered in postinfusion plasmas of patients treated with wet cryoprecipitate, whereas there was a postinfusion loss of large multimers after lyophilized cryoprecipitate and fraction I‐0. These findings indicate that the attainment of a normal BT is the exception rather than the rule after the infusion of three plasma fractions used in the treatment of severe VWD, and that an intact multimeric structure in concentrates and postinfusion plasmas is necessary but not sufficient to sustain a normal BT.
Myeloid lineage specificity and high sensitivity of monoclonal antibody GM 58/8 proves its usefulness as a diagnostic reagent in acute leukemia
Authors: Gupta Amar Das , Dhond Subodh R. , Barbhaya Shakuntala A. , Advani Suresh H.
Published: February 2007

Monclonal antibody (MoAb) GM 58/8 was earlier reported to be directed against an antigen expressed by myeloid progenitors (CFU‐GM), myeloid precursors, granulocytes, and monocytes [5]. Immunophenotyping of 216 cases of acute leukemia [acute myeloblastic leukemia (AML) = 147 and acute lymphoblastic leukemia (ALL) = 69] and 18 cases of chronic granulocytic leukemia in blast crisis (CGLBC) with this antibody showed that GM 58/8 reacted with 92% of AML cases (M1‐M5) and 100% of myeloblastic crisis in CGL cases. All cases of ALL, lymphoblastic crisis in CGL, erythroleukemia, and erythroblastic crisis in CGL were unreactive with GM 58/8. The antibody revealed the myeloid phenotype in an additional 15 cases of otherwise unclassifiable acute leukemia and six cases of CGLBC. Eleven cases of acute “mixed lineage” leukemia were also diagnosed with the help of GM 58/8. The high specificity (100%) and sensitivity (92%) of MoAb GM 58/8 for myeloblastic leukemia is unmatched by almost all previously described myeloid MoAb and proves its usefulness as a single diagnostic reagent for AML and myeloblastic crisis in CGL.
Serum from patients with non‐hodgkin's lymphoma(nhl) inhibits T‐cell colony formation
Authors: Hutchison Robert E. , Tice Diane G. , Davey Frederick R.
Published: February 2007

This study compared T‐cell colony formation in soft agar of lymphocytes from the peripheral blood and lymph nodes of patients with non‐Hodgkin's lymphoma (NHL) with T‐cell colony formation of peripheral blood lymphocytes from normal individuals. Mononuclear cells were separated from other blood and lymph node elements on density gradient columns, phenotyped for T‐ and B‐cell antigens using monoclonal antibodies, and then plated in soft agar cultures. Lymphocytes from peripheral blood and lymph nodes of patients with NHL exhibited less T‐cell colony formation (p < 0.01) than did lymphocytes from normal individuals. This decrease in T‐cell colony formation was not the result of the number of T cells or null cells plated, or differences in proportions of T helper and T suppressor cells. However, when sera from patients with NHL were incubated with normal lymphocytes before plating in soft agar, a decrease in number of T‐cell colonies was observed (p < 0.01). We conclude that peripheral blood and lymph node mononuclear cells from patients with NHL have a decreased ability to form T‐cell colonies in soft agar cultures and that this decrease is related, at least in part, to the presence of serum factor(s).
Erythroblast transferrin receptors and transferrin kinetics in iron deficiency and various anemias
Authors: Muta Koichiro , Nishimura Junji , Ideguchi Hiroshi , Umemura Tsukuru , Ibayashi Hiroshi
Published: February 2007

To clarify the role of transferrin receptors in cases of altered iron metabolism in clinical pathological conditions, we studied: 1 number of binding sites; 2 affinity; and 3 recycling kinetics of transferrin receptors on human erythroblasts. Since transferrin receptors are mainly present on erythroblasts, the number of surface transferrin receptors was determined by assay of binding of 125I‐transferrin and the percentage of erythroblasts in bone marrow mononuclear cells. 1 The number of binding sites on erythroblasts from patients with an iron deficiency anemia was significantly greater than in normal subjects (p < 0.01). Among those with an aplastic anemia, hemolytic anemia, myelodysplastic syndrome, and polycythemia vera compared to normal subjects, there were no considerable differences in the numbers of binding sites. 2 The dissociation constants (Kd) were measured using Scatchard analysis. The apparent Kd was unchanged (about 10 nmol/L in patients and normal subjects. 3 The kinetics of endocytosis and exocytosis of 125I‐transferrin, examined by acid treatment, revealed no variations in recycling kinetics among the patients and normal subjects. These data suggest that iron uptake is regulated by modulation of the number of surface transferrin receptors, thereby reflecting the iron demand of the erythroblast.
Phosphoglycerate kinase San Francisco: A new variant associated with hemolytic anemia but not with neuromuscular manifestations
Authors: Guis M. S. , Karadsheh N. , Mentzer W. C.
Published: February 2007

Phosphoglycerate kinase deficiency is a rare, x‐linked glycolytic defect that, when severe, can be associated with hemolytic anemia, rhabdomyolysis, or neurological disorders. We report here a new phosphoglycerate kinase variant discovered in a boy with severe hemolytic anemia but no evidence of neuromuscular disease or developmental delay. The biochemical properties of the variant enzyme (greatly increased kmATP and km3‐phosphoglycerate; normal pH optimum, electrophoretic mobility, and substrate specificity; resistance to heat inactivation) establish its uniqueness. Separation of light and dense red cells by centrifugation showed no greater loss of phosphoglycerate kinase activity in dense (“old”) variant cells than in normal cells. We postulate that the striking stability of the variant enzyme allows cells capable of protein synthesis to accumulate sufficient enzyme to limit neuromuscular sequelae.
The spectrum of human immunodeficiency virus infection in patients with factor IX deficiency (Christmas Disease)
Authors: Goldsmith J. M. , Variakojis D. , Phair J. P. , Green D.
Published: February 2007

Early reports suggested that hemophiliacs with factor IX deficiency (Christmas Disease) may be at less risk for developing the acquired immunodeficiency syndrome (AIDS) than patients with classic hemophilia. We evaluated 12 factor IX deficient patients for clinical and immunologic abnormalities related to infection with the human immunodeficiency virus (HIV). Antibody to HIV was not detected in these patients prior to 1982. By 1985, 66 percent (eight of 12) patients were seropositive. All three concentrates available commercially before 1985 were associated with seropositivity. Furthermore, seropositive hemophiliacs had received on average significantly more factor IX concentrate than seronegative hemophiliacs (27,825 ± 17,976 (S.D.) versus 1,250 ± 1,500 factor units/year, (p < 0.02). Half of the seropositive individuals had generalized lymphadenopathy with splenomegaly. Two seropositive patients have developed AIDS, one with cryptococcal meningitis and another with a large cell immunoblastic lymphoma. Infection with HIV has occurred with high frequency in hemophiliacs who received unmodified factor IX concentrates.
Systemic lupus erythematosus and sickle hemoglobinopathies: A report of two cases and review of the literature
Authors: Katsanis Emmanuel , Hsu Elizabeth , Luke Koon‐Hung , McKee James A.
Published: February 2007

Two adolescent black females with sickle cell disease who developed systemic lupus erythematosus (SLE) are presented. The recognition of SLE was delayed because all new symptoms were initially attributed to their underlying sickle cell disease. Nine similar cases have been previously reported. The hypothesis that a deficiency of the alternative complement pathway in some patients with sickle hemoglobinopathies predisposes them toward immune complex disorders was not confirmed in our study. Our first patient had normal and our second increased activity of the alternative pathway of complement activation.
High‐dose intravenous IgG therapy in a seven‐week‐old infant with chronic autoimmune hemolytic anemia
Authors: Sasaki Hiroshi , Akutagawa Hiroshi , Kuwakado Katsuji , Uemura Masaru , Emi Isamu
Published: February 2007

A 7‐week‐old male infant tested positive for autoimmune hemolytic anemia. Serological studies revealed a positive Coombs test and a strong antibody with relative anti‐E specificity.

Despite corticosteroid therapy, he frequently suffered severe hemolytic crises. During the course of the disease he had pneumonia, subcutaneous abscess, and sepsis, which were thought to be caused by his immunosuppressive state. His clinical course was chronic and refractory.

Recently, high‐dose intravenous IgG therapy for the treatment of chronic AIHA has been reported, but it has not been successful in the management of adult AIHA. We attempted this therapy in our patient, and successful management was obtained.
A distinct subtype of idiopathic myelofibrosis with bone marrow features mimicking hairy cell leukemia: Evidence of an autoimmune pathogenesis
Authors: Hasselbalch Hans , Jans Henning , Nielsen Preben Løvgreen
Published: February 2007

A young female patient presented with severe anemia and myelofibrosis. The spleen was not enlarged on clinical examination and no leukoerythroblastosis or tear‐drop poikilocytosis was found. A bone marrow biopsy disclosed severe myelofibrosis and many megakaryocytes, which appeared morphologically normal. A striking feature was a heavy spongy infiltration by large lymphocytic cells, which were tartrateresistant acid phosphatase negative and without hairy projections. This bone marrow appearance highly resembled the clear cell appearance of the hairy cell infiltrate in hairy cell leukemia. A diagnosis of acute autoimmune myelofibrosis was made. During high‐dose glucocorticoid therapy the bone marrow fibrosis completely resolved and there was an improvement of peripheral blood values. The disorder is supposed to feature a distinct clinicopathological entity within the syndrome of idiopathic myelofibrosis. The disease should be considered in the differential diagnosis of patients with myelofibrosing disorders, including acute myelofibrosis and hairy cell leukemia.
Maturation of B‐lineage blast crisis cells in chronic myeloid leukemia
Authors: Ng C. S. , Arnold M. , Chan John K. C.
Published: February 2007

A 44 year‐old Chinese male presented with lymphoid blast crisis of chronic myeloid leukemia, in which the blast cells exhibited a pre‐pre‐B cell phenotype (B4+ B1− J5+ 12+smIg−). There was a phenotypic transition during the course of the disease to a more mature B cell phenotype (B4+ B1− J5+ 12+smIgGλ+). The maturation of blast crisis cells may be related to the chemotherapeutic agents used in the treatment of the disease.
Involvement of von willebrand factor in thrombosis following asparaginase‐prednisone‐vincristine therapy for leukemia
Authors: Pui Ching‐Hon , Jackson Carl W. , Chesney Carolyn M. , Abildgaard Charles F.
Published: February 2007

To determine if factor VIII‐von Willebrand factor (vWF) complex is involved in the thrombosis associated with asparaginase‐prednisone‐vincristine induction therapy for acute lymphoblastic leukemia, plasma vWF was analyzed by sodium dodecyl sulfateagarose gel electrophoresis and crossed immunoelectrophoresis. Five patients with cerebral thrombosis were studied; all had a decreased platelet count following the complication. Sequential studies of three patients disclosed changes in plasma vWF multimer pattern. One patient who was studied serially from 2 days before to 1 day after the event, had an increase in unusually large plasma vWF multimers that disappeared after the complication. The other two patients who were studied at presentation subsequently showed a decrease in plasma large vWF multimers, especially remarkable in the patient having the sharpest decrease in platelet count. No appreciable difference in vWF multimer pattern, when compared to normal pooled plasma, was found in the remaining two patients who were only studied at presentation, or in the seven controls who received the same treatment but did not develop thrombosis. Crossed immunoelectrophoretic analyses of two patients tested disclosed a right shift of immunoprecipitin line in one and a left shift in the other. Our findings suggest that the thrombotic complications resulted from platelet agglutination by plasma vWF.