bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrastructural studies of myeloma cells: Observations concerning the Golgi apparatus and intermediate‐size filaments
Authors: Pavelka Margit , Ludwig Heinz
Published: February 2007

Studies on the ultrastructure of tumor cells of 22 multiple myeloma patients revealed hitherto unreported observations concerning the Golgi apparatus and intermediate‐size filaments. Various abnormalities of the Golgi apparatus including displacements of the Golgi stacks, dilatations of cisternae, and massive accumulations of vesicles as well as vacuoles in the Golgi region were found in myeloma cells of 11 patients.

Intermediate‐size filaments forming a fine intracytoplasmic network were apparent in myeloma cells of all 22 patients. In five patients, in addition to this architecture, intermediate‐size filaments were gathered into thick bundles which were primarily but not exclusively located in the perinuclear region.
Intracranial myeloid metaplasia: Diagnosis by CT and Fe52 scans and treatment by cranial irradiation
Authors: Cornfield Dennis B. , Shipkin Paul , Alavi Abass , Becker Joseph , Peyster Robert
Published: February 2007

A patient with longstanding agnogenic myeloid metaplasia developed a progressive dementia. CT scanning demonstrated multiple intracranial masses, and a Fe52 bone marrow scan demonstrated erythroid activity within the masses and confirmed the suspicion of extramedullary hematopoiesis. A potentially hazardous biopsy was avoided, and a course of cranial irradiation was administered, resulting in regression of the masses and clearing of the patient's dementia. Fe52 scintigraphy provides a specific and useful diagnostic approach which may eliminate the need for invasive procedures.
Inhibition of cold insolubility of an IgA cryoglobulin by decanedicarboxylic acid and related compounds
Authors: Lalezari Parviz , Kumar Mahendra , Kumar Kalpana M. , Lawrence Christine
Published: February 2007

Cold insolubility of a serum IgA cryoimmunoglobulin was found to be inhibited by the addition of 1.5 mM sodium decanedicarboxylate in vitro. The patient with the cryoglobulin had advanced multiple myeloma complicated by severe hyperviscosity that caused lethargy and episodic loss of consciousness. Decanedicarboxylic acid administered orally resulted in transient relief of symptoms and the loss of cryoprecipitability of the paraprotein. Further in vitro studies revealed that sodium salts of long‐chain monocarboxylic acids with a minimum of eight carbons, and dicarboxylic acids with a minimum of 12 carbons inhibited cryoprecipitation. Salts of short‐chain carboxylic acids, by contrast, enhanced cryoprecipitation. Sodium phenolate and sodium salts of benzoic acid, 2,4‐DNP, phenylpropionic acid, and salicylic acid were also inhibitory. These latter compounds, which have a ring structure, did not cause precipitation at any concentration. It was demonstrated that the presence of a free carboxylic group was required for these activities; conversion of carboxylic acid to amide resulted in the loss of both the inhibitory and cryoprecipitation‐enhancing effects. Normal plasma, or plasma from five other patients who had IgG, IgM, or mixed‐type cryoglobulinemia, were not affected by any of these compounds. It is suggested that in selected cases of hyperviscosity syndrome associated with cryoglobulinemia, some of these compounds, especially monocarboxylic acids with appropriate chain lengths, or those with a ring structure, may have therapeutic applications.
Chronic myelomonocytic leukemia with a chromosome abnormality (46,XY,20q–) in all dividing myeloid cells: Evidence for clonal origin in a multipotent stem cell common to granulocyte, monocyte, erythrocyte, and thrombocyte
Authors: Shinohara Tamiko , Takuwa Noriko , Morishita Kazuhiro , Ieki Ryuji , Yokota Jun , Nakayama Emiko , Asano Shigetaka , Miwa Shiro
Published: February 2007

In a typical case of chronic myelomonocytic leukemia (CMML), a chromosome abnormality, 46, XY,20q‐, was observed in all the dividing cells including up to 16‐ploid cells in the bone marrow and the blood. As the mitotic figures could be easily seen not only in myelomonocytoid cells but also in erythroblasts in the bone marrow smear, it was concluded that all the cell lineages except lymphocytes had the abnormality. The present case will support the view that the leukemic process in CMML affects a multipotent stem cell rather than a granulocyte‐monocyte committed stem cell.
Increased serum procollagen III aminoterminal peptide in myelofibrosis
Authors: Hochweiss S. , Fruchtman S. , Hahn E. G. , Gilbert H. , Donovan P. B. , Johnson J. , Goldberg J. D. , Berk P. D.
Published: February 2007

Myelofibrosis has been shown to involve an increase in type III collagen in the marrow. The aminoterminal procollagen III (PC III) peptide fragment is released during the production of PC III by fibroblasts and its serum level is therefore a marker for type III collagen synthesis. Using a recently developed sensitive radioimmunoassay, serum levels of PC III peptide were measured in 30 patients with myeloproliferative disease and 23 normal volunteers. Levels were found to be elevated above normal values in patients with polycythemia vera, even more elevated in patients with polycythemia and evidence of secondary myelofibrosis with mycloid metaplasia, and most strikingly elevated in patients with agnogenic myeloid metaplasia and severe marrow fibrosis. There was a significant association between serum levels of PC III peptide and the extent of reticulin fibrosis in bone marrow biopsies. Serum PC III level appears to be a quantitative marker for myelofibrosis.
Analysis of transformation with epstein‐barr virus and phenotypic characteristics of lymphoblastoid cell lines established from patients with hairy cell leukemia
Authors: Sairenji Takeshi , Spiro Robert C. , Reisert Patricia S. , Paquin Louise , Sakamoto Kiyoshi , Shibuya Atsushi , Suilivan John L. , Katayama Isao , Humphreys Robert E.
Published: February 2007

In order to assess the role of Epstein‐Barr virus (EBV) in patients with hairy cell leukemia (HCL), we have sought to characterize 1) the ability of EBV to infect and transform hairy leukemic cells in vitro and 2) the phenotypes of cell lines putatively derived from those leukemic cells. Analysis of EBV‐induced transformation and the kinetics of Epstein‐Barr nuclear antigen (EBNA) induction in leukemic preparations indicated that most leukemic cells were not susceptible to EBV infection but that at least a small subpopulation of leukemic cells could be infected with EBV. Lymphoblastoid cells lines were established after exposure of peripheral blood or splenic cells from HCL patients to B95‐8 or QIMR‐WIL EBV. Splenic leukemic cell preparations were more sensitive targets for EBV transformation than were peripheral blood cell samples. The newly established cell lines, but not long‐established B lines such as Raji, demonstrated high levels of synthesis of p35, (a protein complex expressed abundnatly by cells of a subset of HCL patients) and high levels of tartrate‐resistant acid phosphatase (an enzyme relatively diagnostic for HCL). Lymphoblastiod lines from one patient with HCL expressed lambda light chains and no kappa chains as did the patient's leukemic cells. Virus expression in these lines showed that HCL‐derived lines had spontaneous earley antigen (EA) and viral capsid antigen (VCA) expression Tranforming EBV could be rescued from HCL‐derived cell lines but not from cord blood‐derived lines.
Change of pyruvate kinase (PK) isozymes in classical type pk deficiency and other PK deficiency cases during red cell maturation
Authors: Takegawa S. , Miwa S.
Published: February 2007

Conversion of pyruvate kinase (PK) isozymes during the maturation of erythroblasts in five cases of PK deficiency was compared with that in normal subjects using immunofluorescent antibody techniques. In normal erythroblasts, M2‐type PK was clearly seen at the proerythroblast stage, then markedly declined with cell maturation whereas L‐type PK continued to increase. In two patients with classical type PK deficiency, M2‐type PK was still clearly seen in orthochromatic erythroblast, whereas L‐type PK was hardly detected during maturation. In three patients with other types of PK deficiency, change of L‐type PK was similar to that of normal subjects whereas M2‐type PK was clearly seen even at the later stage of maturation as in classical‐type PK deficiency. The present studies indicate that compensatory M2‐type PK production occurs in the erythroblasts of patients with PK deficiency.
Analysis of T‐cell subsets in B‐cell chronic lymphocytic leukemia: A correlation with the stage of disease
Authors: Mittelman A. , Denny T. , Gebhard D. , Cirrincione C. , Kurland E. , Koziner B.
Published: February 2007

T‐cell subsets were determined by the Leu monoclonal antibodies in the peripheral blood and/or bone marrow of 52 patients with B‐cell chronic lymphocytic leukemia (B‐CLL) not on therapy at the time of study. The diagnosis of B‐CLL required that the leukemic cells expressed surface receptors for “la‐like” antigen, Fc fragment of IgG, mouse red blood cells (MRBC), C3‐coated red cells (EAC), and low density of monoclonal surface immunoglobulin. The Leu‐3a+/2a+ ratio was applied to define the balance between the helper/suppressor subsets in the residual T‐lymphocytes. Most patients showed a decrease in the Leu‐3a+/2a+ ratios at all stages of disease. The decrease in ratio was mainly related to a decrease in the Leu‐3a+ T‐cell subset. The more advanced stages of B‐CLL were associated with lower Leu‐3a+/2a+ ratio, higher total white cell and percent lymphocyte counts. There was no correlation between the proportion of EAC or MRBC rosetting cells and stages of B‐CLL. This analysis further suggests that B‐CLL is an immunosuppressed state that becomes more pronounced in the advanced stages and is characterized by a progressive decrease in the Leu‐3a+ (helper) T‐cell subset.
Intestinal infarction caused by paroxysmal nocturnal hemoglobinuria
Authors: Doukas Michael A. , Dilorenzo Paul E. , Mohler Daniel N.
Published: February 2007

A patient with paroxysmal nocturnal hemoglobinuria of 14 years duration presented with severe abdominal pain and fever. On admission, his hematocrit had fallen to 19% from his usual level of approximately 30%, and stools were positive for occult blood. Dilated loops of small bowel with air fluid levels were noted on radiographs, and sonography revealed free intraperitoneal fluid. Several sections of gangrenous jejunum and ileum were resected at exploratory laparotomy, and mesenteric venous thromboses were present. This is the second report of pathologically proven intestinal infarction in a patient with paroxysmal nocturnal hemoglobinuria who has survived this abdominal emergency with surgical intervention. Although abdominal pain in patients with paroxysmal nocturnal hemoglobinuria has frequently been attributed to mesenteric venous thromboses, this has rarely been documented either during life or at autopsy.
HB F‐Yamaguchi (γ75THR, γ80ASN, γ136ALA) is associated with Gγ‐thalassemia
Authors: Nakatsuji T. , Ohba Y. , Huisman T. H. J.
Published: February 2007

Restriction endonuclease analyses of DNA from a known Hb F‐Yamaguchi heterozygote and three of his relatives have shown a deletion of about 5 kb, which includes one of the γ genes. This abnormality is similar to the Gγ‐thalassemia described recently [4] and is probably caused by an unequal crossing over between ‐Gγ‐ and ‐AγT‐genes. The abnormal ‐GγAγT‐X‐ (X = Asp→Asn at γ80) hybrid gene produces the γ‐Yamaguchi chain at a level usually seen for Gγ chains only.
Tumor interaction with hemostasis: The rationale for the use of platelet inhibitors and anticoagulants in the treatment of cancer
Authors: Al‐Mondhiry Hamid
Published: February 2007

Clinical and experimental observations have firmly established the concept of a two‐way interaction between malignancy and the hemostatic system. On the one hand, certain tumors can activate platelets and the coagulation mechanism in vivo, on the other, a convincing case has been made for the involvement of platelets and fibrin in tumor growth and metastasis. A large number of clinical and experimental studies have been conducted in order to test the efficacy of platelet inhibitors and anticoagulants as adjuvants in the treatment of cancer. Antiplatelet drugs gave variable results, depending on the drug and the tumor system tested. Prostaglandin synthetic pathways by both the host and tumor seem to be an important determinant in the response to platelet function inhibitors. Of the various anticoagulants tested, the coumarin derivatives gave somewhat consistent antitumor effect in certain human and experimental cancer. The antitumor effect of oral anticoagulants does not appear to be a primary drug effect and seems related to their role as vitamin K antagonists. It should be emphasized that although the antitumor potential of antithrombotic agents is a subject of keen interest at the present, their use in treating human cancer is still controversial.
Thalassemia‐like abnormalities of the red cell membrane in hemoglobin E trait and disease
Authors: Dorléac E. , Morlé L. , Gentilhomme O. , Jaccoud P. , Baudonnet C. , Delaunay J.
Published: February 2007

In recent studies, we observed a decrease of KMapp, an abnormally biphasic kinetics of the red cell membrane neutral phosphatase and an increased binding of hemoglobin to the membrane in various forms of β‐thalassemia. Since the gene encoding the β chain (βE chain) of hemoglobin E (HbE) is endowed with some thalassemic characteristics, we studied the erythrocyte membrane in 25 individuals with Hb E trait or disease. The apparent Michaelis‐Menten constant for p‐nitrophenylphosphate (the artificial substrate used) was significantly decreased, as in β‐thalassemia. However, the kinetics was monophasic in all the heterozygotes and in four of the homozygotes. It was biphasic only in the three other homozygotes. Vmax was also significantly reduced, a fact that is masked, when not reversed in β‐thalassemia, owing to the rejuvenation of the red cell population. In 5 mM phosphate buffer (pH 8.00), the binding of Hb E to the erythrocyte ghosts was increased in the homozygotes. In the heterozygotes, Hb A binding was also increased, as is the case in β‐thalassemia. This latter fact suggests that the membrane binding site(s) of hemoglobin is (are) altered. We found a highly significant increase of Hb F in EE subjects. The present study extends to the red cell membrane the β‐thalassemic phenotype associated with the βE gene.
Sideroblastic anemia: Differences in bone marrow erythroid colony (CFUe) growth responses to erythropoietin in plasma clot and methylcellulose cultures
Authors: Lutton J. D. , Ibraham N. G. , Hoffman R. , Ritchey A. K. , Levere R. D.
Published: February 2007

Bone marrow cells from three patients with idiopathic acquired sideroblastic anemia and one with X‐linked sideroblastic anemia were simultaneously cultured in plasma clot and methylcellulose cultures in order to evaluate their erythroid colony (CFUE) cloning potential in these two systems. In contrast to normals, sideroblastic anemia bone marrow cells demonstrated a marked ability to form erythropoietin (Epo)‐independent CFUE in methylcellulose culture, and were inhibited in their ability to generate CFUE in plasma clot culture even in the presence of Epo.

Addition of citrated plasma to methylcellulose cultures inhibited Epo‐independent CFUE growth, but not Epo‐dependent growth, by both a normal and patients' bone marrow cells. These results demonstrate that bone marrow cells from some patients with sideroblastic anemia can undergo Epo‐independent and Epo‐dependent CFUE growth in vitro, and that there is a marked difference in CFUE growth depending on the type of clonal culture method used. It is suggested that the culture microenvironment, plasma, and sensitivity to Epo may be contributing factors which allow specific clones of sideroblastic anemia CFUE‐forming cells to proliferate in vitro.
“Leukemic” pattern of in vitro growth in a patient with Down syndrome and transient myeloproliferative disorder
Authors: Mendelow Barry , Krawitz Selma , Cohn Richard , Bernstein Renée
Published: February 2007

Peripheral blood cells from a female infant with Down syndrome and over 60% circulating myeloblasts were cultured in soft agar. Growth was virtually restricted to cluster formation, and cluster‐forming cells resided almost exclusively in the very light density fraction (SG < 1.062). Morphological assessment of clusters revealed no evidence of cellular differentiation beyond the blast cell stage. Despite receiving no specific chemotherapy, the peripheral blood normalized within 2 months, and there was no evidence of leukemia when the patient died aged 1 year from cardiac pathology. The findings indicate that caution should be exercised when assessing prognosis on the basis of in vitro growth characteristics in such patients.
In vitro neutrophil‐erythrocyte rosette formation mediated by a serum factor (IgG)
Authors: Mirchandani Ila , Palutke Margarita , Kithier Karel , Tabaczka Pamela , Suffian Jacqueline
Published: February 2007

In vitro neutrophil‐erythrocyte rosette (NER) formation occurred in the peripheral blood of an elderly man. This caused problems in cross‐matching for blood transfusion initially but was resolved by performing crossmatches at 37°C because this phenomenon was temperature‐dependent. NER formation was independent of complement and of the type of anticoagulant used. NERs were induced using normal control cells with the patient's plasma, serum, and the IgG fraction of serum. The resetting factor was adsorbed by heterologous group‐specific erythrocytes, but not by leukocytes. No neutrophil antibodies were identified.
Preparation of young red cells for transfusion using the fenwal CS 3000 cell separator
Authors: Pisciotto Patricia , Kiraly Thomas , Rosen Debra , Paradis Lois , Kakaiya Ram M. , Morse Edward E.
Published: February 2007

A pheresis procedure was devised to isolate young red cells by centrifugation using the Fenwal CS 3000 continuous flow cell separator. Young red cell enriched products were collected in a 2.5–3‐hour procedure. Large numbers of white cells and platelets were collected with the red cells, but cryopreservation and subsequent washing removed 99% of the contaminating cells. At the completion of all processing a product yielding 70% of the total hemoglobin content of a standard frozen/deglycerolized red cell unit was produced. Autologous radiochromium survival of young red cells, measured in 12 normal donors, showed an average 24‐hour recovery of 89.9% with a T50Cr of 40.8 days. In paired autologous studies (N = 4) there was a mean increase of 35% in the observed T50Cr of young red cells as compared to standard frozen red cells.
Human monocyte interaction with antibody‐coated platelets. I. General characteristics
Authors: Court Wayne S. , Christensen A. Kent , Sacks Roger W. , Lobuglio Albert F.
Published: February 2007

The interaction of human monocytes with antibody‐coated and normal platelets was studied using an assay system that employed rate zonal centrifugation to separate monocyte‐associated (bound) platelets from free platelets. At a monocyte:platelet ratio of 1:10, monocytes bound 21.2 ± 6.6% of antibody‐coated platelets and less than 2.2 ± 1.3% of control platelets. Monocyte binding of antibody‐coated platelets was rapid and inhibited by monomeric IgG and staphylococcal protein A. Specific binding was positively related to the number of monocytes present and the amount of IgG displayed on the platelet surface. Transmission and scanning electron micrographs illustrate the membrane binding of antibody‐coated platelets to monocytes and suggest that phagocytosis of platelet targets occurs as well. Thus, these observations indicate that monocytes can participate in Fc‐receptor binding of anti‐PLA1‐sensitized platelets. This novel assay may be useful in the analysis of monocyte‐macrophage Fc‐receptor interaction with platelets sensitized with IgG from both iso‐ and autoimmune disorders as well as in the characterization of treatment modalities which may alter monocyte Fc‐receptor recognition and binding.
Kinetics of platelet density subpopulations in splenectomized mongrel dogs
Authors: Mezzano Diego , Aranda Eduardo , Foradori Arnaldo , Rodríguez Soledad , Lira Pablo
Published: February 2007

Autologous 51Cr‐platelet kinetic studies were performed in splenectomized mongrel dogs. Mean survival time of PRP‐platelets was 5.4 ± 1.5 (SD) days (n = 6). The curves, though slightly curvilinear, showed mostly a linear type of decay, denoting that platelet removal from the circulation is mainly determined by aging of the cells. High‐density (HD) and low‐density (LD) platelet cohorts were isolated in Stractan gradients from samples drawn daily after infusion of labeled platelets. Specific radioactivity in HD cohorts declined rapidly postinfusion (T1/2 = 1.3 days), but specific radioactivity in LD platelets increased for 2 days and steadily declined for 4 days thereafter (n = 6). Labeled HD platelets, comprising 11.7% of the total population, lived significantly longer in circulation than LD platelets (19.1% of the total population) (n = 3). The patterns of decay of the radioactivity, however, do not have all the characteristics of pure age‐cohort survival curves; 3.7 days after the infusion of labeled HD platelets, the specific radioactivity in LD cohorts was six times higher than on day 1, but attained only 20% of the initial specific radioactivity in HD platelets. After the infusion of labeled LD platelets no radioactivity was recovered in circulating HD cohorts.

These findings indicate that mongrel dog platelets decrease in density with aging, but also that platelet density heterogeneity is in part determined during the thrombopoietic process. These data are consistent with those of other authors in rabbits and rhesus monkeys, but contrast with the observations that platelets in humans, baboons, and Macaca fasicularis monkeys increase in density with age, suggesting that the displacement of platelets toward compartments of either higher or lower density depends on the species under study.
Successful treatment of chronic refractory pure red cell aplasia with antithymocyte globulin: Correlation with in vitro erythroid culture studies
Authors: Mangan Kenneth F. , Shadduck Richard K.
Published: February 2007

Two contrasting cases of chronic refractory pure red cell aplasia (PRCA) responsive to a commercial preparation of horse antihuman thymocyte globulin (ATG) are reported. Both cases were refractory to trials of cyclophosphamide, corticosteroids, and plasmapheresis. One patient developed a reticulocytosis after a single intravenous infusion of ATG; the other patient responded after administration of 14.7 g of ATG over a 28‐day course. At presentation, erythroid progenitors (CFU‐E and BFU‐E) in one patient were normal; in the second patient, the number of erythroid progenitors was severely reduced. Neither patient had a serum IgG inhibitor to progenitor cells as judged by in vitro erythroid colony studies. Both patients had increased numbers of marrow T‐cells and co‐culture studies in one case were consistent with T‐cell‐mediated suppression of erythropoiesis. These studies confirm that ATG is a useful agent in the treatment of refractory PRCA. However, ATG may not act by removal of T suppressor cells in all cases.
Spurious automated red cell values in warm autoimmune hemolytic anemia
Authors: Weiss Gary B. , Besman J. David
Published: February 2007

Two patients with warm autoantibodies to their red cells had a mean cell volume artifactually elevated by red cell agglutination. Red cell size distribution histograms directly showed doublets and triplets of normal‐size red cells. This phenomenon is similar to the spurious macrocytosis previously reported due to cold agglutinins, but was not reversible by warming.
Erythrocyte membrane phosphorylation in aging rats
Authors: Kumar Raj
Published: February 2007

By sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE), the protein profile and autophosphorylation of plasma membranes of red cells from 3‐, 9‐, 18‐, and 30‐month‐old rats was examined. No major changes in SDS‐PAGE protein profiles were noticeable. However, endogenous (auto) and exogenous phosphorylation in the presence of (γ−32P)ATP showed an age‐dependent increase in 32P utake. pH optimum was between 8.0 and 9.0 for all age groups. Cyclic AMP was without effect on either endogenous or exogenous phosphorylation. Further analysis of the autophosphorylation reaction by quantification of autoradiograms obtained from SDS‐PAGE gels displayed an age‐dependent increase in phosphorylation of bands 2, 3, 4.1, and 4.5 [nomenclature of Fairbanks et al. Biochemistry 10:2606, 1971] and of several other minor bands. The data imply that alteration in red cell membranes may occur during aging of rats causing an enhancement in endogenous kinase activity and possibly in the number of phosphate acceptor sites as well.
Reproducibility of the French‐American‐British classification of acute Leukemia: The southwest oncology group experience
Authors: Head David R. , Savage Richard A. , Cerezo Lizardo , Craven Catherine M. , Bickers John N. , Hartsock Robert , Hosty Thomas A. , Saiki John H. , Wilson Henry E. , Morrison Francis S. , Coltman Charles A. , Hutton John J.
Published: February 2007

After initial French‐American‐British (FAB) diagnosis by a multiinstitutional Southwest Oncology Group panel, slides of acute leukemia cases were recirculated to panel members for second review. The reproducibility of the FAB classification is analyzed. The classification is reproducible in the 70% range in panel reviewer hands and allows remarkable reproducibility in the morphologic and cytochemical distinction of acute lymphoid leukemia (ALL) from acute myeloid leukemia (AML). The limitations of a morphologic and cytochemical classification of acute leukemia are discussed. A simplification of the FAB system, merging M1, M2, and M4 as M7, is proposed; this simplification improves the system's reproducibility.
Intravenous gammaglobulin in refractory immune thrombocytopenic purpura: Efficacy with or without concomitant steroid therapy
Authors: Abrams Ross A. , Aster Richard , Anderson Tom
Published: February 2007

Two patients with immune thrombocytopenic purpura (ITP) refractory to conventional management with steroids and splenectomy were treated with 5‐day courses of intravenous gamma globulin (Gamimune‐Cutter), 400 mg/kg/day. Improvement was observed in both cases even while steroids were being tapered. In each case when thrombocytopenia subsequently recurred or worsened, further therapy with IV gamma globulin without concomitant steroids was followed by definite increase in platelet numbers. These observations confirm that the Cutter preparation of IV gamma globulin is efficacious in the management of refractory ITP and suggest that in this clinical setting response to IV gamma globulins can occur without concomitant administration of corticosteroids.
Some studies with a monoclonal antibody directed against human fibrinogen
Authors: Francis Susan E. , Joshua Douglas E. , Exner Thomas , Kronenberg Harry
Published: February 2007

Some properties of a monoclonal antibody generated against the fibrinogen component of a factor VIII preparation were investigated. The antibody bound with equal affinity in solid phase radioimmunoassays to fibrinogens isolated from both normal patients and patients with von Willebrand disease. It reacted in a sensitive immunoassay of plasma fibrinogen. The specificity of the antibody was confined to the parent molecule with no significant inhibition of fibrinogen binding by the fibrinogen degradation products (FDPs) X, Y, D, or E. The antibody had no significant effect on the activated partial thromboplastin time and prothrombin time of normal plasma. However, it prolonged the thrombin time as determined by the Clauss chronometric fibrinogen method. During fibrinogen lysis by plasmin immunoreactivity of fibrinogen to the antibody was lost at the same rate as the clottable fibrinogen content determined by the Clauss assay. The lack of reactivity of the antibody with FDPs makes it a suitable reagent for investigating plasmin activity as well as studying fibrinogen and fibrin. These findings suggest that the epitope of the antibody lies within the polar protruberance of the carboxy terminal end of the Aα chain of fibrinogen and is destroyed by plasmin cleavage.
Botrocetin‐ and polybrene‐induced platelet aggregation in platelet‐type von willebrand disease
Authors: Takahashi Hoyu , Nagayama Reizo , Hattori Akira , Shibata Akira
Published: February 2007

It has been reported that botrocetin, a Bothrops venom factor, induces platelet aggregation dependent on von Willebrand factor (vWF), and that platelet aggregation induced by Polybrene, a synthetic polycation, is enhanced by vWF. This report describes the platelet aggregability on stimulation with botrocetin and Polybrene in four patients with platelet‐type von Willebrand disease (vWD) who showed increased platelet aggregation with low concentrations of ristocetin as the result of a platelet abnormality. Enhanced platelet aggregability with botrocetin was observed in platelet‐rich plasma (PRP) from the patients. Platelet aggregation induced by botrocetin in a mixture of normal washed platelets and patient plasma was either decreased or normal, being dependent on the amount of plasma vWF. In contrast with ristocetin and botrocetin, Polybrene did not cause increased aggregation of patient PRP. Polybrene aggregated normal washed platelets less extensively in the presence of patient plasma than normal plasma. These studies demonstrated that botrocetin induced heightened interaction between platelets and vWF, but Polybrene did not, in platelet‐type vWD, and that the enhanced responsiveness of patient platelets to botrocetin is related to an intrinsic platelet abnormality.
Replacement therapy in platelet‐type von willebrand disease
Authors: Takahashi Hoyu
Published: February 2007

The response to infusions of cryoprecipitate and factor VIII concentrate was studied in a patient with platelet‐type von Willebrand disease (vWD) who showed lack of the large multimers of von Willebrand factor in plasma, increased platelet aggregation with low concentrations of ristocetin, and in vitro platelet aggregation by normal plasma. The cryoprecipitate and factor VIII concentrate to be infused induced platelet aggregation when added to patient platelet‐rich plasma at concentrations higher than 0.86 U/ml and 3 U/ml of factor VIII‐related antigen (VIIIR:Ag), respectively. Administration of cryoprecipitate (41.9 U VIIIR:Ag/kg body weight) was followed by a shortening of the bleeding time, and hemostasis was achieved during tooth extractions. Factor VIII concentrate (70.2 U VIIIR:Ag/kg) failed to correct the prolonged bleeding time and proved ineffective to control the gum bleeding. No significant diminution of the platelet count was observed following any infusion. These results indicate that cryoprecipitate is hemostatically effective and safe when infused in such a dosage, but factor VIII concentrate is not effective in platelet‐type vWD in analogy to what is observed in various types of vWD.
Interaction between a serum factor and T lymphocytes in gaucher disease
Authors: Bassan Renato , Montanelli Alessandro , Barbui Tiziano
Published: February 2007

A defective formation of E rosette from peripheral lymphocytes was observed in five patients with Gaucher disease. Evidence is shown that the reduction of E rosetting capacity is due to serum factors since it was induced in normal lymphocytes incubated with patients' sera. It is likely that ferritin, found elevated in the patients, might be involved in this inhibitory phenomenon. This disfunction might play a role in the high incidence of cancer in Gaucher patients.
Increased numbers of marrow basophils may be associated with a t(6;9) in ANLL
Authors: Pearson Marilyn G. , Vardiman James W. , Le Beau Michelle M. , Rowley Janet D. , Schwartz Stuart , Kerman Shelly L. , Cohen Maimon M. , Fleischman Elena W. , Prigogina Elena L.
Published: February 2007

We have characterized another subset of acute nonlymphocytic leukemia (ANLL) based on the cytogenetic and morphologic findings in a group of nine patients. Five patients had chromosomal analyses performed at the University of Chicago, two patients were studied at the All‐Union Cancer Research Center in Moscow, and one patient each was studied at the University of Maryland and at Fairfax Hospital in Fairfax, Virginia. All nine patients had a reciprocal translocation involving the short arm of chromosome 6 and the long arm of chromosome 9 [t(6;9)(p23;q34)]. The patients, four males and five females, ranged in age from 5 to 51 years; the median age of 38 years is lower than that typically seen in ANLL. Only two of eight treated patients entered a complete remission. Classification of bone marrow morphology according to FAB Cooperative Group criteria revealed AML‐M1 in one patient, AML‐M2 in four, and AMMoL‐M4 in three. One patient had refractory anemia with excess blasts (RAEB) which evolved to AML‐M2. All bone marrow specimens showed severe myelodysplasia, with Auer rods present in seven of the nine cases. Of note was the particular prominence of bone marrow basophils (greater than 1%) in eight of the nine (89%) patients. Among 160 evaluable patients with ANLL de novo seen at the University of Chicago whose cells lacked a t(6;9), only five (3%) had greater than 1% basophils in the marrow aspirates. It is of interest that the breakpoint in 9q involves the same chromosomal band as that in the t(9;22) observed in chronic myelogenous leukemia (CML), in which increased basophils are a prominent feature. Thus, the association of the t(6;9) with increased bone marrow basophils in ANLL may provide additional insight into the chromosomal location of genes regulating the production and/or maturation of basophils.
Multiple myeloma with crystalline inclusions in most hemopoietic cells
Authors: Gabriel Laurence , Escribano Luis , Perales Jose , Bellas Carmen , Odriozola Jesus , Navarro Jose‐Luis
Published: February 2007

Intracytoplasmic inclusions were observed at light and electron microscopy in the cells of most of the hemopoietic series, including erythroblasts, in a case of multiple myeloma IgG kappa. The inclusions were of crystalline nature, surrounded by smooth membrane. An indirect immunoperoxidase method on thick sections confirmed their immunoglobulin G kappa nature. The fact that crystals were observed in various hemopoietic series suggests that, except for the plasma cells, their presence is more likely due to phagocytosis than to synthesis and, therefore, that they are not a clone marker.
Heparin‐induced thrombocytopenia and recurrent thromboembolism in siblings
Authors: Kosfeld Rodney E. , Lansing Allan M. , Masri Zahi , Liu Yong K.
Published: February 2007

Two brothers with heparin‐induced thrombocytopenia and multiple arterial and venous thromboembolism affecting peripheral vessels are described. Heparin‐dependent antiplatelet antibody was detected using platelet aggregometry in both patients. Although these observations may be coincidental, the possibility of familial occurrence of this adverse reaction to heparin cannot be excluded with certainty.
Acute nonlymphocytic leukemia following treatment of testicular cancer and gastric cancer with combination chemotherapy not including alkylating agents: Report of two cases
Authors: Pedersen‐Bjergaard Jens , Rørth Mikael , Avnstrøm Søren , Philip Preben , Hou‐Jensen Klaus
Published: February 2007

Acute nonlymphocytic leukemia following combination chemotherapy not including alkylating agents or radiotherapy was observed in one patient treated for testicular cancer and in another treated for gastric cancer. Both patients presented clinical, cytologic, and cytogenetic findings uncharacteristic for secondary acute nonlymphocytic leukemia. It is discussed whether these two cases of leukemia indicate a risk of secondary leukemia following chemotherapy with cisplatinum and adriamycin.
Natural killer cells—toward clinical application
Authors: Schattner Ami , Duggan David B.
Published: February 2007

Natural killer (NK) cells are non‐B, non‐T lymphoid cells of uncertain lineage that rapidly recognize and lyse a large variety of tumor or virus‐infected cells, without the need for either prior sensitization or major histocompatability complex (MHC)‐dependent recognition. Though some essential problems in understanding NK cell function are still unsolved, considerable progress has been achieved in recent years following the identification of the characteristic large granular lymphocyte (LGL) morphology of NK cells and their purification, the study of their function at the single‐cell level, and the cloning of mouse and human NK cell lines. Activated mainly by interferon (IFN), as well as important producers of IFN, NK cells appear to have a distinct role in immunoregulation in addition to their postulated major role in “immune surveillance,” for which convincing in vivo data has accumulated. Future clinical applications may therefore include manipulations of the NK system through expansion and activation of patient's LGL or the use of cloned human NK cell lines.
A lymphoproliferative disorder of Tγ cells with the phenotype of cytotoxic suppressor T‐cell
Authors: Amagasaki Tatsuhiko , Shibata Junji , Yao Eiichi , Nishino Kenji , Yamada Yasuaki , Sadamori Naoki , Tomonaga Masao , Kinoshita Kenichiro , Ichimaru Michito
Published: February 2007

A 25‐yr‐old Japanese male showed unique Tγ cell proliferation different from cases reported previously. His clinical and hematological features were characterized by persistent high fever and the appearance of large lymphocytes with abundant cytoplasm and azurophilic granules in the peripheral blood (11% of the leukocyte differential count) and the ascitic fluid. These lymphocytes showed the ability to bind the Fe portion of IgG and they beared the antigen of cytotoxic/suppressor T‐cell defined by monoclonal antibodies. T‐cells from this patient suppressed the immunoglobulin production of normal B‐cells by pokeweed mitogen, although a polyclonal hypergammaglobulinemia was observed in the serum. Chromosomal abnormality indicated the malignant nature of the proliferating Tγ cells in this patient. The clinical, hematological, and immunological findings characterized the disease of this patient as a distinct entity among the lymphoproliferative disorders of T‐cell origin.
Clinical manifestations and erythrocyte adhesion to endothelium in sickle cell syndrome
Authors: Wautier J. L. , Galacteros F. , Wautier M. P. , Pintigny D. , Beuzard Y. , Rosa J. , Caen J. P.
Published: February 2007

Painful vasocclusive episodes are one of the most prominent pathological features of sickle cell disease. In addition to abnormal shape and poor deformability, increased adhesion of red cells to endothelium has been reported. On several occasions, we have studied the adhesion of erythrocytes from 30 patients with mixed sickle cell syndromes to evaluate the influence of clinical conditions. The percentage of erythrocytes adhering was significantly higher when erythrocytes from sickle patients were compared with controls (p < 0.01). Furthermore, adhesion was significantly higher when the patients were in crises (p < 0.01), and the highest values of all were observed in patients with inflammatory conditions. To investigate the possibility that a limited population of red cells could be responsible for the increase in red cell adhesion, we have measured the HbS concentration in the different washes and found that the HbS concentration was higher in the last washes compared to the first washes. Sickle red cells capable of protein synthesis (young red cells) were labelled with [3H] leucine. The adhesion to endothelial cells of [3H] leucine‐labelled red cells was higher than that of the 51Cr‐labelled red cells from the same patient. On the other hand, the most dense sickle red cells separated by density gradient adhered to a greater extent than the light red cells. This apparent discrepancy could be partly explained by the presence of [3H] leucine‐labelled red cells in the dense fractions of sickle red cells separated by stractan gradient.
Erythrocyte (Ca+2+Mg+2)‐ATPase activity: Increased sensitivity to oxidative stress in glucose‐6‐phosphate dehydrogenase deficiency
Authors: Shalev Oded , Lavi Vardiella , Hebbel Robert P. , Eaton John W.
Published: February 2007

The effect of the thiol‐oxidizing agent diamide on erythrocyte (Ca+2+Mg+2)‐ATPase activity was measured in normal and glucose‐6‐phosphate‐dehydrogenase‐deficient (G6PD−) cells. Although the enzyme activity before the oxidative stress was similar in both groups, diamide induced a markedly greater inhibition in the enzyme activity in the G6PD− cells than in the normal controls. These data indicate dependence of erythrocyte (Ca+2+Mg+2)‐ATPase, in part, on the redox status of the cell. The increased vulnerability of (Ca+2+Mg+2)ATPase to oxidative stress in G6PD− may be of pathophysiological relevance to their premature destruction in oxidant‐induced hemolysis.
Spleen irradiation in chronic lymphocytic leukemia (CLL): Palliation in patients unfit for splenectomy
Authors: Aabo Kristian , Walbom‐Jorgensen Sven
Published: February 2007

In 22 patients with CLL given 30 courses of spleen irradiation, 23 responses were observed (77%, 95% confidence limits, 58‐90%). Response was defined as reduction in palpable spleen size accompanied by relief of symptoms (pain, abdominal discomfort, and sweating) or improvement in hypersequestration or hemolytic anemia. Reduction in leukocyte count alone was not regarded as response. All responses were partial. The median response duration was 1 year. Subsequently, three patients underwent splenectomy. The median survival from the beginning of spleen irradiation was 2.5 years (range: 1 month‐>5 years). Only six patients had minor side effects from the gastrointestinal tract. The hematologic effect was most pronounced on the white blood cell count, but also the platelet count was affected. It is concluded that spleen irradiation is a gentle and effective alternative in CLL patients suffering from splenomegaly (pain and hypersplenism), refractory to chemotherapy and glucocorti‐costeroids and unfit for splenectomy. Splenic irradiation may also be used with benefit preoperatively before splenectomy in patients with excessive splenomegaly and hypersplenism.
Hb regina or α2β296(FG3)LEU → VAL: A high oxygen affinity variant discovered by cation‐exchange HPLC
Authors: Devaraj R. , Wilson J. B. , Huisman T. H. J.
Published: February 2007

Results are reported of studies of the hemoglobin from one member of a Canadian family with a mild erythrocytosis. This variant, which accounted for about 40% of the hemoglobin, could be separated from Hb A and Hb A2 by cation‐exchange chromatography. Micro methodology allowed the characterization of a Leu → Val replacement at position β96(FG3). Hb Regina has an increased oxygen affinity, which adequately explains the hematological observations.
Stomatocytic transformation of red blood cells after marathon running
Authors: Reinhart Walter H. , Chien Shu
Published: February 2007

We studied red blood cell morphology in two marathon runners before, immediately after, and 1 day after a marathon race. A discocyte‐stomatocyte transformation was found by light microscopy of wet preparations and also by scanning electron microscopy, with about one‐half the erythrocytes becoming cup‐shaped after the marathon. These changes were completely reversible within 18 hr after the race.
Tartrate‐resistant acid phosphatase staining of monocytes in gaucher disease
Authors: Troy Kevin , Cuttner Janet , Reilly Margaret , Grabowski Gregory , Desnick Robert
Published: February 2007

Cytochemical studies were performed on peripheral blood from 30 patients with type 1 Gaucher disease. In 29 of the patients, peripheral blood monocytes stained positively for tartrate‐resistant acid phosphatase, whereas monocytes from 18 normal individuals and 14 patients with monocytosis did not. In the Gaucher patients, the percentage of monocyte positivity for tartrate‐resistant acid phosphatase ranged from 2 to 97. There was no correlation between the percent monocyte staining and the degree of disease severity, as measured by hepatosplenomegaly, pancytopenia, or extent of bone disease, for the group as a whole. In Gaucher patients who had not undergone splenectomy, however, there was a significant correlation between percent monocyte staining and the degree of hepatosplenomegaly, anemia, and thrombocytopenia. The presence of tartrate‐resistant acid phosphatase may be secondary to the lysosomal accumulation of glucosyl ceramide within these monocytes, although this remains to be confirmed. If so, these circulating cells may represent precursors of the Gaucher cells in tissues. Tartrate‐resistant acid phosphatase staining of peripheral blood monocytes may be useful as a diagnostic marker for Gaucher type 1 disease and for further studies on the pathogenesis of the disease.
Treatment of hemophilic arthritis with D‐penicillamine: A preliminary report
Authors: Corrigan James J. , Kolba Karen S. , Gall Eric P. , Trombley Joyce , Damiano Mary Lou , Meredith Keith , Jeter Monette
Published: February 2007

Current medical management programs for established joint diseases in hemophiliacs are unsatisfactory and do not modify the eventual outcome. D‐penicillamine, a drug effective in the proliferative synovitis of rheumatoid arthritis, was evaluated in a rabbit model of hemarthroses‐induced arthritis and in four hemophiliacs with chronic synovitis. The animals had intra‐articular injections of citrate (left knees) and autologous citrated whole blood (right knees). Eight weeks later, the rabbits were divided into two groups: no treatment and D‐penicillamine (50 mg/kg/day, IM) until sacrificed at 6 months. The saline‐injected joints showed no inflammation and no iron deposition. The blood‐injected knees showed iron deposition in both groups, the D‐penicillamine animals had marked suppression of chronic inflammation. Of the four patients treated, three had clinical responses (reduction in synovial thickness, reduction in number of bleeds in the affected joint). One patient, who did not respond, developed mild‐moderate proteinuria. Those patients who responded received between 5.3 and 7.1 mg/kg/day of the drug. Mild abnormalities in platelet aggregation were seen in the responders. This preliminary study suggests that D‐penicillamine is beneficial in the chronic synovitis/arthritis induced by hemarthroses. Further trials are recommended.
Lupus anticoagulant: An analysis of the clinical and laboratory features of 219 cases
Authors: Gastineau Dennis A. , Kazmier Francis J. , Nichols William L. , Bowie E. J. Walter
Published: February 2007

To define clinical and laboratory characteristics of the lupus anticoagulant (LA), we reviewed our experience (219 subjects). Subjects were divided into group A, those with the LA and the diagnosis of lupus erythematosus, group B, those with the LA but nonlupus diagnoses, and group C, those with drug‐related lupus syndromes.

The typical laboratory findings consisted of a prolonged and inhibited plasma clot time (an average of 1.9 times control time) which was proportionately more prolonged than the partial thromboplastin time or activated partial thromboplastin time (APTT) (average 1.3 times control). Ninety‐eight percent had a prolonged plasma clot time and 94% had a prolonged partial thromboplastin time. The prothrombin and thrombin times were prolonged in 33 and 25% of subjects, respectively. Washed platelets shortened the APTT in the 22 subjects so tested. Monoclonal protein peaks were seen in 7% of patients.

Seventeen episodes of bleeding were observed, but in all but one instance there was another hemostatic defect present. In the 18 patients who underwent major operations, there were no hemorrhagic complications. Fifty‐eight episodes of thrombosis were observed with the same incidence in group A (25%) as in group B (26%).

Bleeding is rare with the LA but thrombosis is common even without SLE and lupuslike syndromes. The plasma clot time in platelet‐rich plasma is more prolonged, and in our experience, is more sensitive in detecting the lupus anticoagulant than is the partial thromboplastin time.