bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet IgG Fc receptor
Authors: Kelton John G. , Smith James W. , Santos Aurelio V. , Murphy William G. , Horsewood Peter
Published: February 2007

The glycoprotein localization of the platelet binding site for the Fc IgG has been the subject of debate. We attempted to resolve this issue by relating the binding of radiolabeled IgG immune complexes composed of heat‐aggregated IgG to platelets from 1) healthy individuals; 2) an individual with Bernard‐Soulier syndrome lacking glycoproteins Ib and IX; and 3) a patient with Glanzmann's thrombasthenia lacking glycoproteins IIb and IIIa. The binding of IgG complexes to platelets was determined by measuring the specific binding of radiolabeled heat‐aggregated IgG to washed platelets in a plasma‐free mileu. 125I aggregated IgG bound to normal platelets in a saturable and concentration‐dependent fashion. Specific binding could be inhibited by a 50‐fold excess of purified Fc, but not by F(ab')2. Identical binding curves were obtained by using platelets from a patient with Glanzmann's thrombasthenia and a patient with Bernard‐Soulier syndrome, indicating that the platelet Fc receptor is not carried on glycoproteins Ib, IIb, IIIa, or IX. We then measured the binding of radiolabeled detergent‐solubilized platelets to IgG fixed to a solid matrix. A 40‐kD platelet fragment bound to the immobilized IgG following passage across a density gradient. Confirmation of the Fc specificity of the interaction was shown by inhibition of platelet glycoprotein binding by excess IgG or purified Fc but not F(ab')2. The electrophoretic mobility decreased slightly after reduction, which indicated the existence of at least one intrachain disulfide bond. Treatment with high salt solutions or urea did not solubilize the receptor, which indicated that it was an integral protein. Enzyme studies showed that the platelet Fc receptor was not digested by neuraminidase, but neuraminidase treatment altered mobility by about 3 %. In addition, treatment of platelets with trypsin or pronase did not affect its function as measured by the binding of 125I‐IgG aggregates to enzyme‐treated platelets, but did prevent its detection when using radioimmunoprecipitation studies. The platelet Fc receptor is a 40‐kD, integral protein without interchain disulfide bonds.
Chronic lymphocytic leukemia in china
Authors: Boggs Dane R. , Chen Shu Chang , Zhang Zhi‐Nan , Zhang An
Published: February 2007

Chronic lymphocytic leukemia (CLL) is a very common form of leukemia among middle‐aged and elderly persons in Western countries. In the Japanese, or in those with Japanese ancestry born and living in the USA, CLL is rather rare. It is also rare in China, but convincing data to support this statement are found primarily in the Chinese literature. We have reviewed previously unpublished data from Peking Union Medical College (PUMC) concerning the frequency of CLL among adult patients with the four common types of leukemia. Of 4,174 such patients (1952–1986), 4.6% had CLL; 22.9% chronic myeloid leukemia (CML); 50.3% acute myeloid leukemia (AML); and 22.3% acute lymphoblastic leukemia (ALL). This low frequency of CLL is none the less higher than that found in a multiinstitutional collection of Chinese patients with leukemia. Various clinical and laboratory aspects of a carefully studied, previously published group of patients with CLL from PUMC were compared to similar published findings in patients from the University of Utah. No differences in the overall nature of the disease were detected between these groups. However, not unexpectedly, the duration of symptoms before the diagnosis was made longer in Chinese than in USA patients and the proportion diagnosed at a time when no CLL related symptoms had been noted was less in Chinese. Neither differences in life span in the two populations nor an excess of CML, AML, and ALL at the expense of CLL were viable hypotheses to explain the rarity of CLL in China. We suggest that the dearth of CLL in Chinese is on a genetic basis, as it is thought to be in the Japanese.
Platelet function in acute respiratory failure
Authors: Carvalho Angelina C. , Quinn Deborah A. , Demarinis Sandra M. , Beitz Julie G. , Zapol Warren M.
Published: February 2007

To assess the role of platelets in thrombohemorrhagic complications of acute respiratory failure (ARF), we studied platelet function in 13 ARF patients admitted for intensive care, in six acutely ill intensive care patients without evidence of acute lung injury (non‐ARF), and in 10 normal subjects. Platelet counts in ARF and non‐ARF patients were similar to the normal range. The bleeding time of the ARF patients (8.5 ± 0.9 min) was significantly longer (p < 0.01) than the normal (4.8 ± 0.2 min) but similar to non‐ARF patients (5.4 ± 0.8 min). The bleeding time prolongations in ARF patients were unrelated to platelet concentration. Platelet aggregation induced by ADP and thrombin was normal in both ARF and non‐ARF patient groups. The epinephrine response was impaired in one non‐ARF patient and in three ARF patients; collagen‐induced aggregation was absent in two ARF patients, with a prolonged bleeding time. Levels of VIII:C and vWF in both groups of patients were similar to the normal level, but VIIIR:Ag levels in ARF patients (407 ± 45% of normal) were higher (p < 0.01) than in both non‐ARF patients (210% ± 10%) and normal subjects (106% ± 4). The electrophoretic mobility of VIIIR:Ag was abnormal in ARF patients. The prolonged bleeding time in ARF patients appears to result from the qualitative and quantitative VIIIR:Ag defect. β‐Thromboglobulin levels were greater (p < 0.01) in ARF patients (87.6 ± 6.9 ng/ml; p < 0.001) than in non‐ARF patients (46.2 ± 3.1 ng/ml) or in normal subjects (25.3 ± 2.5 ng/ml p < 0.0001). However, platelet factor 4 plasma levels in ARF patients (18 ± 1.6 ng/ml) did not differ from those in non‐ARF patients (15.0 ± 3.0 ng/ml), but both were significantly different from normal (6.1 ± 0.8 ng/ml). Plasma thromboxane B2 (T × B2) levels were not different from normal values in either ARF or non‐ARF patients, but 6‐keto‐PFG1α levels were significantly reduced (p < 0.01) in ARF patients (215 ± 43 pg/ml) compared to normal values (381 ± 34 pg/ml). Non‐ARF patients had 6‐keto‐PGF1α levels (285 ± 111 pg/ml) midway between the normal values and those of ARF patients. Our results suggest that in vivo platelet activation occurs in ARF. ARF patients have quantitative and qualitative platelet defects that may contribute to thrombotic and hemorrhagic complications.
In vitro induction of myeloid surface markers in a rare case of acute leukemia
Authors: Drexler Hans G. , Coustan‐Smith Elaine , Gignac Suzanne M. , Jani Harsha , Victor Hoffbrand A.
Published: February 2007

The phenotypic marker profile of a case of acute leukemia is described; its immunophenotype is unique in that the blast cells were initially negative for a wide panel of monoclonal antibodies (McAbs) to surface and intracytoplasmic antigens and for the nuclear enzyme terminal deoxynucleotidyl transferase. Morphological and cytochemical examination suggested an acute myeloid leukemia (AML), but the cells were unreactive with anti‐myeloid McAbs. Treatment with the phorbol ester 12‐0‐tetradecanoylphorbol 13‐acetate (TPA) induced the cells to differentiate morphologically to macrophage‐like cells and led to the expression of surface antigens that could be detected by antimyeloid McAbs. It is not clear whether these cells represent a rare subclass of leukemic cells that are void of any characteristic surface markers but have the potential to differentiate along the myeloid axis, or whether the antigens were masked by an unknown process.
Fibrinogen giessen I: A congenital homozygously expressed dysfibrinogenemia with Aα 16 Arg← his substitution
Authors: Alving Barbara M. , Henschen Agnes H.
Published: February 2007

Clinical reports are published for only two patients with homozygously expressed congenital dysfibrinogenemia. The patients, both of whom have a bleeding diathesis, have amino acid substitutions in the fibrinogen molecule at Aα 16 Arg←Cys and Aα 19 Arg←Ser, respectively. We report that a third patient with dysfibrinogenemia (fibrinogen Giessen I) is homozygous for Aα 16 Arg← His. Although this patient has had excessive postpartum bleeding, she has had normal hemostasis throughout several minor surgical procedures and hysterectomy. Elucidation of the amino acid alterations in patients with dysfibrinogenernia may expand our understanding of structural determinants of fibrinogen that are critical to its function in vivo.
Establishment of a common acute lymphoblastic leukemia cell line (LC4‐1) and effects of phorbol myristate acetate (PMA) on the surface antigen expression of the cell line
Authors: Yoshimura Tomohide , Mayumi Mitsufumi , Yorifuji Tohru , Kim Kwang‐Myong , Heike Toshio , Miyanomae Takeshi , Shinomiya Keisuke , Mikawa Haruki
Published: February 2007

A common acute lymphoblastic leukemia (ALL) cell line, designated LC4‐1, was established from peripheral blood mononuclear cells of a patient with acute non‐T‐cell ALL. LC4‐1 cells were characteristically positive for Ia, B4, and common ALL antigens (CALLA), but negative for B2, Tac, T3, T4, T8, T11, and M1 antigens and E‐rosette formation. Approximately 30% of LC4‐1 cells expressed detectable amounts of B1 antigens. LC4‐1 cells expressed neither Epstein‐Barr‐virus–associated nuclear antigen (EBNA), cytoplasmic immunoglobulins (cIg) nor surface immunoglobulins (sIg). Gene rearrangements had already occurred in LC4‐1 in the D‐J region of immunoglobulin heavy chain genes, but not in T‐cell receptor (β‐chain) genes, suggesting that LC4‐1 is a progenitor cell line of B‐cell lineage earlier than pre‐B‐cells.

The expression of cell surface antigens of LC4‐1 was changed by treatment with 4‐phorbol 12‐myristate 13‐acetate (PMA) (0.1 ng/ml) for 2 days. Before treatment with PMA, about 98% of LC4‐1 cells were positive for B4, CALLA, and Ia. However, following treatment they lost CALLA expression without any change in expression of Ia and B4. There was no change in B1‐positive population. The change in surface antigens on LC4‐1 cells seems to be due to differentiation induced in the cells by PMA. These results support the hypothesis that CALLA is a differentiation antigen and suggest one possible differentiation pathway for pre‐B‐cells.
Modified end‐point glycerol hemolysis assay as a screening test for hereditary spherocytosis that requires no venipuncture
Authors: Judkiewicz Luba , Szczepanek Andrzej , Bugała Irena , Bartosz Grzegorz
Published: February 2007

The high specifity of the “pink test” for the detection of hereditary spherocytosis has been confirmed. A modification of the test is proposed that requires only 10 μl of blood taken without anticoagulant (a “direct pink test”), thus eliminating the necessity of venipuncture, especially cumbersome in newborns and infants.
High‐dose chemoradiotherapy with syngeneic bone marrow transplantation for multiple myeloma: A case report and literature review
Authors: Wolff Steven N. , McCurley Thomas L. , Giannone Leonard
Published: February 2007

We had the opportunity to treat a patient with progressive heavily pretreated multiple myeloma with high‐dose chemoradiotherapy with hematopoietic rescue by syngeneic bone marrow transplantation. The patient was a 53‐year‐old male who had previously received melphalan, prednisone, 1,3‐bis (2‐chloroethyl)‐l‐nitrosourea (BCNU), vincristine, and standard radiation therapy. At the time of bone marrow transplantation, he had increasing bone pain, increasing M‐protein (IgG kappa), and a bone marrow diagnostic of myeloma. The transplant regimen consisted of cyclophosphamide, 60 mg/kg intravenously for 2 days, and total body irradiation—1,200 rads given as 200‐rad fractions, twice daily for three days. The transplant course was complicated by confusion, herpes simplex mucositis, fever, and two episodes of idiopathic diffuse interstitial pneumonia. Over the next 2 years the patient did well and was in immunologic and bone marrow complete remission. Unfortunately, 3 years after treatment, the myeloma relapsed with detectable M‐protein. Three and one‐half years after transplant, clinical relapse occurred with bone pain and lytic lesions necessitating additional radiation and chemotherapy. Salvage therapy has produced clinical improvement and the patient is alive almost 4 years from transplant and almost 7 years from diagnosis. Although intense chemoradiotherapy did not cure this patient, substantial control of a refractory tumor was observed. This case, together with other cases of intense therapy for myeloma which are reviewed in this paper, support the concept of high‐dose therapy and should foster further investigation of high‐dose therapy.
High‐dose intravenous gammaglobulin (IVG) in neonatal immune thrombocytopenia
Authors: Suarez Carlos R. , Anderson Craig
Published: February 2007

Recent reports suggest that intravenous gammaglobulin (IVG) may be an effective treatment modality in patients with immune thrombocytopenia (ITP). Two newborns with isoimmune thrombocytopenia secondary to HLA‐A2 and PLA1 platelet antigen incompatibilities with their respective mothers and two newborns with thrombocytopenia secondary to maternal ITP were treated with IVG 400 mg/kg/day × 5 days. One patient was exposed to steroids in utero; only one mother was thrombocytopenic at the time of delivery.

All patients were severely thrombocytopenic on day 1 of treatment with mean platelet count of 5.7 × 109/L. All had petechiae and positive quaiac stools, and patients with isoimmune thrombocytopenia had CT scan evidence of intracranial bleeds. The mean platelet count after 24 hr was 26.7 × 109/L and the average platelet increase was 21 × 109/L and 33 × 109/L at 24 and 48 hr, respectively. The two cases with isoimmune thrombocytopenia had sustained platelet increases; the two cases secondary to maternal ITP had transient platelet elevations. IVG can rapidly elevate the platelet count in these patients, especially those with severe bleeding manifestations.
Partial deficiency of protein 4.1 in hereditary elliptocytosis
Authors: Lambert S. , Zail S.
Published: February 2007

Protein 4.1, an important component of the red cell membrane skeleton, was quantitated relative to protein 3 after sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS‐PAGE) of membranes isolated from red cells of members of 14 kindreds with hereditary elliptocytosis (HE) who reside in South Africa. A partial deficiency of protein 4.1 (mean 30% reduction) was inherited in autosomal dominant fashion in five white kindreds giving a frequency of 0.36 of HE families studied. Immunoblots of membrane proteins separated by SDS‐PAGE and probed with a monoclonal antibody to protein 4.1 did not reveal any proteolytic fragments in the 4.1‐deficient subjects that could account for the reduction of this protein. These studies draw attention to the relatively high frequency of this condition as a cause of HE in white subjects in this country.
Reliability of absent platelet dense bodies as a diagnostic criterion for Hermansky‐Pudlak syndrome
Authors: Witkop Carl J. , Krumwiede Marcy , Sedano Heddie , White James G.
Published: February 2007

The clinical, pigmentary, and ceroid storage manifestations of the Hermansky‐Pudlak syndrome (HPS) triad of albinism, hemorrhagic diathesis, and ceroid storage disease are variable. Therefore, a rapid and accurate method of diagnosing HPS is needed. Platelets of 66 albinos were examined by electron microscopy for the presence or absence of dense bodies. Results show that patients reexamined over a period of 1 year had consistent findings. Those lacking dense bodies (15) when first examined also lacked dense bodies when reexamined a year later, and they had evidence of ceroid storage. Those with dense bodies when first examined (8) also had dense bodies when reexamined, did not have evidence of storage disease, and had types of albinism other than HPS. Of 20 propositi lacking dense bodies, all 32 albino relatives also lacked dense bodies, while 6 albino relatives of 6 propositi with dense bodies also had dense bodies in their platelets. The evidence supports the concept that HPS is a distinct genetic and biochemical disease in which the components of the triad are the result of a single genetic defect, either a point mutation or a small deletion. Comparison of whole mount preparations with thin section preparations of 13 albinos shows that whole mount preparations are an accurate and rapid method for diagnosing HPS. The most consistent diagnostic feature of HPS is lack of platelet dense bodies.
Dysfunctional α‐globin genes in hemoglobin H disease in blacks: Variation in restriction fragment size permits the detection of the ‐α/‐αT genotype
Authors: Safaya S. , Mullaney P. , Rieder R. F.
Published: February 2007

Hemoglobin H (HbH) disease is most often due to deletion of three of the four α‐globin genes (genotype ‐ ‐ ‐ ‐/‐α). In black subjects although the ‐α/chromosome is common, the ‐ ‐/haplotype is very rare and few examples of HbH disease have been detected. We have studied three black siblings with HbH by restriction endonuclease mapping of the α‐like gene complex (5′‐ζ‐Ψζ‐Ψα2‐Ψα1‐α2‐α1‐3′) using ζ‐ and α‐ specific probes. The presence of size differences in the previously described hypervariable region between the ζ and ζΨ genes results in a restriction fragment length polymorphism which permitted the detection of single α genes on both number 16 chromosomes in these subjects. Quantitative DNA hybridization by a slot‐blot technique confirmed that their genomes contained two α‐globin genes. The results establish that in these black subjects HbH disease is associated with dysfunctional α‐globin genes (genotype: ‐α/‐αT).
Regulation of adult and embryonic genes in human leukemia cells
Authors: Deisseroth Albert , Lyding Judith
Published: February 2007

In this article, we have reviewed studies showing that altered expression of regulatory genes results in activation of embryonic genes in human leukemia cells. These data have led to important new insights as to how mutations in regulatory genes can lead to disease states in man.
Cause of death in hemophilia a patients in the United States from 1968 to 1979
Authors: Aronson David L.
Published: February 2007

Death data on 949 hemophiliacs for the years 1968–1979 have been analyzed. The median age at death has increased from 33 to 55 years. There was no evidence of new diseases caused by the more intensive therapy during this time interval. The leading infectious disease was hepatitis, accounting for eight deaths. Only one acute hepatitis death was listed after 1974, when sensitive tests for hepatitis B antigen screening of plasma were implemented. Cirrhosis was a primary or associated cause of death in 76 cases (8%) and pneumonia was a primary or associated cause of death in 62 deaths (6.5%). The types of malignancies in hemophiliacs were similar to those in the male US population with no evidence of excessive retrovirus malignancies prior to infection with HIV‐1.
Prolonged activated partial thromboplastin time of unknown etiology: A prospective study of 100 consecutive cases referred for consultation
Authors: Kitchens Craig S.
Published: February 2007

The activated partial thromboplastin time (aPTT) is frequently used to assess overall competency of the intrinsic pathway of coagulation. An abnormal value may be caused by any of several abnormalities along this pathway or by many other variables including the presence of inhibitors, poor collection of the sample, or variables in the laboratory. When the cause for the prolongation is unknown to the requesting physician, the hematologist may be consulted. In this prospective study, the cause and perceived hemostatic risk to 100 consecutive patients referred to us for consultation regarding a prolonged aPTT of previous unknown cause were evaluated. We found that these abnormal aPTTs may be either indicative of a hemostatic defect, in 50% of the cases, or of no particular risk, in 36% of the cases. In 14%, the aPTT was artifactually prolonged. Most (81%) patients with a prolonged aPTT due to a hemostatic defect had an abnormal hemostatic history but some (19%) did not. Even among true abnormal tests, the degree of abnormality indicated little or nothing about hemostatic competency. We conclude that the cause of an abnormal aPTT is more important than the result itself. These data may be of use to those who consult on such matters.
Sickle cell trait in a white Jewish family presenting as splenic infarction at high altitude
Authors: Shalev Oded , Boylen Alice L. , Levene Cyril , Oppenheim Ariella , Rachmilewitz Eliezer A.
Published: February 2007

We report the presence of sickle cell trait in several members of a white Jewish family. The trait was discovered when the propositus developed massive splenic infarction at high altitude. No erythrocyte markers characteristic of African ancestry were detected in any of the family members. This is the first bona fide documentation of sickle trait among white Jews.
Human T‐lymphotropic virus type I‐associated benign transient immature T‐cell lymphocytosis
Authors: Ehrlich Garth D. , Han Tin , Bettigole Richard , Merl Stuart A. , Lehr Bruce , Tomar Russell H. , Poiesz Bernard J.
Published: February 2007

We describe a case of human T‐lymphotropic virus type I (HTLV‐I)‐associated transient benign immature T‐cell lymphocytosis in a black female patient, which over the course of several months underwent spontaneous complete remission. The patient presented with a white blood cell count of 20,000/μl and a T4/T8 ratio of 1.7:1. The majority of cells appeared to be lymphoid in origin, and cell marker analyses established that the circulating lymphocytes were predominantly immature T‐cells. HTLV‐I was detected at this time by a p19 indirect immunofluorescent slide assay. Over a 1‐month period of time the patient's clinical status evolved into a mature T‐lymphocytosis with a T4/T8 ratio of 4.5:1. HTLV‐I was detected by anti‐p19 immunofluorescence by cell sorter analyses and by dot‐bloc nucleic acid hybridization. Serological testing demonstrated that the patient had anti‐HTLV‐I antibodies and antimembrane antibodies specific for an HTLV‐I producing cell line. In a competitive HTLV‐I ELISA assay only HTLV‐I proteins could effectively compete out the seroreactivity. The patient also had a high serum level of soluble interleukin‐2 (IL‐2) receptors, which is associated with HTLV‐I infection. This is the first reported case of immature T‐lymphocytosis in a patient infected with HTLV‐I. The patient's HTLV‐I markers disappeared with time, and her lymphocytosis subsequently spontaneously resolved. She remains disease free and virus negative after 2 years of follow‐up study.
Rapid response to 2′‐deoxycoformycin in advanced hairy cell leukemia after failure of interferons alpha and gamma
Authors: Lembersky Barry C. , Ratain Mark J. , Westbrook Carol , Golomb Harvey M.
Published: February 2007

A patient with advanced hairy cell leukemia initially had a short‐lived minor response to interferon alpha therapy and failed to respond to interferon gamma. Subsequent treatment with 2′‐deoxycoformycin (dCF) administered biweekly for 12 wk resulted in a complete hematological remission which has continued for 16 months without additional therapy.
Clinical presentation and natural history of patients with essential thrombocythemia and the Philadelphia chromosome
Authors: Stoll D. B. , Peterson P. , Exten R. , Laszlo J. , Pisciotta A. V. , Ellis J. T. , White P. , Vaidya K. , Bozdech M. , Murphy S.
Published: February 2007

Six women presented with the clinical picture of essential thrombocythemia (ET) without the anemia, marked splenomegaly, and extreme leukocytosis characteristic of chronic myelogenous leukemia (CML). All had the Philadelphia chromosome on karyotype analysis of the bone marrow. Peripheral basophilia was present in four cases, providing a clinical clue that the Philadelphia chromosome might be present. Marrow biopsy showed granulocytic hyperplasia and either small megakaryocytes or sheets of megakaryocytes with marked atypia, findings that are more typical of CML than ET. The clinical importance of finding the Philadelphia chromosome in patients who seem to have ET is in assessing prognosis. ET generally follows a chronic, indolent course. However, five of these six patients who had the Philadelphia chromosome underwent clinical transition to the accelerated phase of CML or blastic leukemia in 4–7 years.
Effect of methotrexate on the deoxyuridine suppression test: Results with different cell preparations
Authors: Kanazawa Shoichiro , Iwasa Saori , Iseki Toru , Okuda Keiko , Kondo Haruki , Okuda Kunio
Published: February 2007

Recently, the deoxyuridine suppression test was used to detect folate deficiency. Several cell preparations were used in this test, and the sensitivity of the test seems to vary with them. We used whole blood (micro‐dU test) and bone marrow cells for the deoxyuridine suppression test, and the effects of methotrexate were compared. [3H]Thymidine incorporation into DNA was highest when the concentration of methotrexate was 1 μM in the whole blood culture and bone marrow culture. Methotrexate concentrations from 100 nM to 1 mM did not affect the results of the micro‐dU test. However, the bone marrow deoxyuridine test became abnormal with methotrexate, and the abnormality in test values was corrected by the addition of N5‐formyltetrahydrofolate. Differences in the results between the micro‐dU test and the bone marrow deoxyuridine suppression test seem to represent specificity of each dU test.
Combined assay of adenosine deaminase, purine nucleoside phosphorylase, and lactate dehydrogenase in the early clinical evaluation of B‐chronic lymphocytic leukemia
Authors: Corrons Joan Lluis Vives , Rozman Ciril , Pujades Maria Assumpció , Colomer Dolors , Vila Encarna Perez , Anegon Ignacio , Gallart Teresa , Puiggrós Jordi Vives , Viñolas Nuria , Montserrat Emili
Published: February 2007

The levels of adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), lactic dehydrogenase (LDH), and LDH isoenzyme patterns (LD1 to LD5) have been measured in lymphocyte extract from 28 patients with B‐chronic lymphocytic leukemia (B‐CLL). The activities of ADA, PNP, and LDH have been correlated with two morphological groups of B‐CLL classified according to the percentage of large, nongranular, atypical lymphocytes (AL) in peripheral blood: “typical” B‐CLL (less than 10% of AL, 21 cases) and “atypical” B‐CLL (10–25% of AL, seven cases). Patients with atypical B‐CLL had significantly (P < 0.001) higher activities of ADA (0.46 ± 0.17 U/109 cells), PNP (1.74 ± 1.0 U/109 cells), and LDH (48.3 ± 9.7 U/109 cells) than patients with typical B‐CLL (ADA, 0.29 ± 0.1 U/109 cells; PNP, 0.58 ± 0.23 U/109 cells; and LDH, 29 ± 10 U/109 cells). In addition, the “treatment‐free period” was also signficantly (P < 0.025) shorter in the group of atypical B‐CLL compared with the typical B‐CLL group. No clear‐cut statistical differences in lymphocyte surface markers or in several other prognostic factors between the two subgroups of B‐CLL were found. The present study supports the idea that in B‐CLL the simultaneous determination of ADA, PNP, and LDH might be helpful in better understanding the pathophysiology, prognosis, and natural history of the disease.
Mean platelet volume is increased in hyperthyroidism
Authors: Ford H. C. , Toomath R. J. , Carter J. M. , Delahunt J. W. , Fagerstrom J. N.
Published: February 2007

In 28 unselected patients with hyperthyroidlsm, platelet count, platelet hematocrft, mean platelet volume, and platelet distribution width were measured at the time of presentation and again when the patients were euthyroid. On return to the euthyroid state, there were highly significant falls in the mean values of the mean platelet volume (16% decline, P < 0.001) and the platelet hematocrit (16% decline, P < 0.001) and a slight but highly significant increase in the mean value of the platelet distribution width (2% increase, P < 0.01). A decline in mean platelet volume was observed in 24 of 28 patients (86%); three patients showed no change. There was no significant change in the mean value of the platelet count. The observed effects of thyrotoxicosis on platets appeared to be largely independent of the well‐known effects on erythrocytes and white blood cells. An increase in mean platelet volume is a regular feature of hyperthyroidism that has not previously been described.
Cerebral thrombosis in a newborn with a congenital deficiency of antithrombin III
Authors: Brenner B. , Fishman A. , Goldsher D. , Schreibman D. , Tavory S.
Published: February 2007

An Israeli Arab family with type I antithrombin III (AT‐III) deficiency with several affected symptomatic members in three generations is reported. The propositus presented with deep vein thrombosis and pulmonary emboli associated with gestation.

The propositus infant presented at the age of 2 weeks with superior sagittal and rectus sinus thrombosis.

Hereditary AT‐III deficiency should be considered in infants with cerebral thrombosis, especially if they have a family history of thromboembolism. The role of prophylactic therapy by AT‐III concentrates in these infants should be further assessed.
Myelopoietic effect of bone marrow fibroblasts cultured from patients with myelofibrosis
Authors: Wang Jen C.
Published: February 2007

Bone marrow fibroblasts (BMF) have been shown to be able to support granulopoiesis. The present studies were designed to see whether BMF in patients with agnogenic myeloid metaplasia (AMM) are also able to support granulopoiesis. Myeloid colonystimulating activity (CSA) was assayed in BMF derived from the three groups of patients. 1) Group I: Patients with hip fracture but without underlying hematological disease; patients with solid tumor but without bone marrow metastasis; and patients with iron deficiency anemia. 2) Group II: Patients with myeloproliferative disorders other than AMM. 3) Group III: Patients with AMM or myelofibrosis with prior history of polycythemia vera. CSA was determined in a bilayer agar culture system inwhich BMF served as a feeder layer and either mouse or human marrow cells were employed as target cells. There was no difference of CSA production by BMF among these three patient groups. These studies suggest that BMF cultured from patients with myelofibrosis exhibit similar myeloid stimulating activity as do BMF from other patients. A significant correlation was also found between CSA production by BMF and white blood cell counts in patients with myelofibrosis (group III). This suggests that BMF may have a role in either supporting or producing CSA for granulopoiesis in myelofibrosis.
Red cell vacuoles: Their size and distribution under normal conditions and after splenectomy
Authors: Reinhart Walter H. , Chien Shu
Published: February 2007

The frequency of occurrence of vacuoles in red blood cells was studied by transmission electron microscopy. Small vacuoles were found in about 13% of the cell sections, and they had a mean diameter of 130 ± 72 nm (mean ± SD). It can be estimated that there were about 20 small vacuoles per erythrocyte. The frequency of vacuoles was similar in density‐separated cell fractions. In splenectomized patients, the small vacuoles were 4 times more frequent; there was again no difference in vacuole density between top and bottom fractions of density‐separated red blood cells. The bottom fraction of red blood cells from splenectomized patients, however, had a high incidence of large vacuoles (> 300 nm in diameter) and clustering of small vacuoles. These large vacuoles were probably the result of aggregation and fusion of small vacuoles, and their size allowed detection by light microscopy. Hence, the well‐known “pocked” or “pitted” red blood cells of splenectomized individuals were more frequent in the bottom fraction. We conclude that small vacuoles occur normally in erythrocytes, that they tend to cluster and fuse during cell aging, and that the spleen is capable of removing these structures when they reach a certain size.
Platelet‐derived growth factor is decreased in patients with myeloproliferative disorders
Authors: Katoh Osamu , Kimura Akiro , Kuramoto Atsushi
Published: February 2007

Platelet‐derived growth factor (PDGF) has been suggested to play some role in the pathogenesis of myelofibrosis frequently encountered in patients with myeloproliferative disorders (MPD). In this study we measured PDGF activity and PF4 content in circulating platelets of patients with MPD. Both factors were lower than those of normal controls. PDGF activity in patients with myelofibrosis was slightly lower than in those without fibrosis. However, when adjusted to whole blood volume, there was a positive correlation between platelet count and PDGF activity per ml whole blood. Nevertheless, no correlation was found between activity and grade of bone marrow fibrosis. These results may support the idea that an abnormal release of PDGF occurs from platelets or megakaryocytes in the bone marrow environment, resulting in the stimulation of fibroblast proliferation, and hence, the occurrence of myelofibrosis in patients with MPD.
Procainamide‐associated pancytopenia
Authors: Shields Anthony F. , Berenson Jeffrey A.
Published: February 2007

A 42‐year‐old male developed thrombocytopenia and anemia along with agranulocytosis during treatment with procainamide. Bone marrow hypoplasia was evident on biopsy, and the patient was without evidence of systemic lupus erythematosis. He had prompt marrow recovery on drug withdrawal. While procainamide‐induced agranulocytosis has been reported on a number of occasions, this is only the second case of pancytopenia.
Prognostic value of clonal chromosomal abnormalities in patients with primary myelodysplastic syndromes
Authors: Gyger Martin , Infante‐Rivard Claire , D'Angelo Giovanni , Forest Lorraine , Lussier Pauline
Published: February 2007

Chromosome analyses were carried out on bone marrow cells from 43 consecutive patients with primary myelodysplastic syndromes (MDS), classified according to the French‐American‐British (FAB) cooperative group criteria. The objective was to evaluate the prognostic value of clonal chromosomal abnormalities and of an excess of blasts for early death from acute nonlymphocytic leukemia (ANLL) and/or bone marrow failure (BMF). Patients were subdivided into two main groups: (1) refractory anemia without an excess of blasts (RAWEB), grouping patients with refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS), and (2) refractory anemia with an excess of blasts (RAEB), grouping patients with refractory anemia with an excess of blasts (RAEB) and refractory anemia with an excess of blasts in transformation (RAEBt). There were 29 patients with RAWEB and 14 with RAEB. The median time of observation was 26 months for RAWEB and 12 months for RAEB. Ten RAWEB patients (34%) and 11 RAEB patients (78%) had clonai chromosomal abnormalities. Among the ten RAWEB patients with clonal abnormalities, one (10%) died from ANLL, while of 19 RAWEB patients with a normal karyotype, two (10%) died from ANLL or BMF. The median survival for patients with RAWEB and an abnormal karyotype was not reached. In contrast, eight of the 11 RAEB patients with clonal chromosomal abnormalities (74%) died from ANLL or BMF. The median survival in this sub‐group was 7 months. By using a Cox proportional hazard regression analysis, it was determined that a karyotype abnormality was not a significant predictory of survival once the contribution of the RAWEB/RAEB variable was taken into account. Being in the RAEB group was associated with a relative risk of 10.6 of dying from ANLL or BMF (β = 2.36, standard error (SE) = 0.68,P= .0001). We conclude that classifying patients according to an excess of blasts will lead to a better prediction of survival than determining karyotype abnormality.
DNA damage in intact cells induced by bacterial metabolites of chloramphenicol
Authors: Isildar Mike , Jimenez Joaquin J. , Arimura Grace K. , Yunis Adel A.
Published: February 2007

Four chloramphenicol (CAP) metabolites known to be produced by intestinal bacteria were examined with respect to their capacity to induce DNA damage in intact cells. The induction of DNA single‐strand breaks in Raji cells, activated human lymphocytes, and human marrow cells was assayed by the alkaline elution technique. One of the four compounds tested, dehydro‐CAP, was capable of inducing DNA single‐strand breaks in all three cell systems at concentrations of 10−4 M. This effect is comparable to that observed previously with nitroso‐CAP, the nitroreduction intermediate of CAP. The nitroreduction of dehydro‐CAP by human bone marrow cell homogenate was detected by the production of the corresponding amino derivative amounting to 5.6 × 10−5M from 2 × 10−3M substrate under aerobic conditions. In sharp contrast, nitroreduction of CAP by bone marrow could not be demonstrated. The genotoxicity of dehydro‐CAP, its relative stability compared to the nitroso‐CAP, and its nitroreducibility by bone marrow suggest that this bacterial metabolite of CAP may play a key role as a mediator of aplastic anemia in the predisposed host.
Ehrlichiosis: A cause of bone marrow hypoplasia in humans
Authors: Pearce Carolyn J. , Conrad Marcel E. , Nolan Patrick E. , Fishbein Daniel B. , Dawson Jacqueline E.
Published: February 2007

Infection with Ehrlichia canis should be suspected in patients with fever, headache, malaise, leukopenia, thrombocytopenia, and a history of recent exposure to ticks. The cytopenia is caused by bone marrow hypoplasia which may be severe. The disease may be confused with spotless Rocky Mountain spotted fever but can be differentiated from this infection serologically with acute and convalescent sera. In humans, recovery has occurred with and without antibiotic therapy. However, prompt antibiotic therapy is advised prior to serologic studies, especially in immunocompromised individuals, splenectomized persons, and patients with AIDS—who may develop a more overwhelming rickettsial infection.
Absence of immunoglobulin and T‐cell receptor gene rearrangements in myelodysplastic syndromes and acute nonlymphocytic leukemias
Authors: Wainscoat J. S. , Fey M. F. , Pilkington S. , Summers C. , Oscier D. G.
Published: February 2007

The arrangement of the immunoglobulin and T‐cell receptor genes has been analysed in 72 cases of primary myelodysplastic syndrome and 17 cases of acute nonlymphocytic leukemia. DNA was extracted from bone marrow aspirates, digested with at least two restriction enzymes, and hybridised with probes for the joining region of the immunoglobulin heavy chain gene, the constant region of the T‐cell receptor β chain gene, and the joining region of the T‐cell receptor γ chain gene. All cases showed germline arrangements of the immunoglobulin and the T cell receptor genes. Thus, true interlineage infidelity, myeloid to lymphoid, is a rare occurrence in myelodysplasia and in myeloid leukemias.
Neonatal alloimmune thrombocytopenia: Spontaneous in utero intracranial hemorrhage
Authors: Burrows Robert F. , Caco Chris C. , Kelton John G.
Published: February 2007

Neonatal alloimmune thrombocytopenia is an uncommon but important cause of thrombocytopenia in infants. Because of the severity of the thrombocytopenia, some of these infants will have intracranial hemorrhage with resultant long‐term disability. Obstetricians and neonatologists have recommended delivery by caesarean section and the rapid institution of appropriate treatment for the infant; however, it is theoretically possible that a hemorrhagic event could precede the delivery and consequently not be prevented by these perinatal interventions. In this report we describe a neonate in whom the diagnosis of alloimmune neonatal thrombocytopenia was suspected because of antenatal ultrasound evidence of intracerebral hemorrhage. This case demonstrates the importance of antenatal fetal assessment and indicates the need for the development of therapeutic strategies to maintain fetal hemostasis.
Early transfusion reactions due to acquired anti‐IgA antibodies in a patient with acute lymphoblastic leukemia
Authors: Parikh P. M. , Iyer Y. S. , Mehta B. C.
Published: February 2007

We report transfusion reactions due to acquired anti‐IgA antibodies in a 32‐year‐old woman with acute lymphoblastic leukemia. Previously, such reactions have been reported only after several hundred transfusions. In our patient they commenced within the first few transfusions.
Plasmin‐α2‐plasmin inhibitor complex in plasma of patients with disseminated intravascular coagulation
Authors: Takahashi Hoyu , Hanano Masaharu , Takizawa Shin‐Ichiro , Tatewaki Wataru , Shibata Akira
Published: February 2007

Plasmin‐α2‐plasmin inhibitor (α2PI) complex, an indicator of in vivo plasmin generation, was measured in the plasma of 48 patients with disseminated intravascular coagulation (DIC), by enzyme‐linked immunosorbent assay (ELISA). Plasmin‐α2PI complex was markedly elevated to 7.9 ± 4.26 mg/liter (mean ± SD) in DIC at presentation, with normal values at less than 0.8 mg/liter. The concentration of plasmin‐α2PI complex changed in parallel with the course of DIC and decreased to 1.9 ± 1.49 mg/liter (n = 28) in remission. Among various underlying disorders, DIC, in patients with acute promyelocytic leukemia, had the highest complex levels (mean 10.8 mg/liter), and septic patients had the lowest levels (mean 3.4 mg/liter). No significant correlation was found between FDP and plasmin‐α2PI complex. These results indicate that the quantitative assay of plasmin‐α2PI complex in plasma would be valuable in the assessment of hyperfibrinolysis in DIC.
Copper deficiency and sideroblastic anemia associated with zinc ingestion
Authors: Simon Sheryl R. , Branda Richard F. , Tindle Barbara H. , Burns Stanley L.
Published: February 2007

Anemia and neutropenia developed in a man who took pharmacologic doses of supplemental zinc. Laboratory investigation showed high zinc level, hypocupremia, low ceruloplasmin level, and ringed sideroblasts. All resolved after withdrawal of zinc. Self‐administered zinc appears to have caused severe copper deficiency, with secondary anemia and neutropenia. Physicians should be aware of this deleterious and completely reversible effect of megadose mineral therapy. Zinc ingestion or exposure should be considered in the differential diagnosis of unexplained anemia, leukopenia, or sideroblastic anemia.
Thymoma and pancytopenia
Authors: Lyonnais Jean
Published: February 2007

A case of thymoma associated with aplastic anemia is presented. Various therapeutic me dalities have been tried and a complete remission finally obtained by antithymocyte globulin.
Plasmapheresis in the management of heparin‐associated thrombocytopenia with thrombosis
Authors: Nand Sucha , Robinson John A.
Published: February 2007

Heparin‐associated thrombocytopenia with thrombosis (HATT) is fatal in 29% and leads to limb amputation in another 21% of patients. Patients with arterial thrombosis do worse than do those with venous thrombosis alone. Heparin‐associated thrombocytopenia is mediated through IgG or IgM immunoglobulin fractions and is believed to be an immune phenomenon, with heparin acting as a hapten. In addition, endothelial injury may be responsible for the development of thrombosis. Heparin‐induced platelet aggregation persists for weeks to months after its withdrawal in these patients. Acute management of HATT includes surgical thrombectomy, thrombolytic therapy, dextran, ancrod, lowmolecular‐weight heparin, and antiplatelet agents, but overall results remain unsatisfactory. We report the use of plasmapheresis, along with aspirin and dextran, in a patient with HATT. The patient experienced pain relief in 1 day; the heparin‐associated platelet aggregation test became negative in 5 days, and there was functional salvage of the affected limb. We suggest that plasmapheresis may be an effective therapy in the management of HATT.
Acetylcholinesterase in the human erythron. I. Cytochemistry
Authors: Koekebakker Marijke , Barr Ronald D.
Published: February 2007

The successful demonstration and localisation of acetylcholinesterase (AChE), in cells by a cytochemical technique requires maximal expression of enzyme activity, minimal loss of AChE and precise, quantitative generation of reaction product at the actual site of the protein in vivo. These requirements are addressed in a standard technique that has been modified to avoid or optimise fixation and to exhibit enzyme activity under close‐to‐physiological conditions of osmolality, pH, and temperature. With these refinements and with the use of a variety of substrates and enzyme inhibitors of different specificities, true AChE was demonstrable on the membrane of erythrocytes and in the nucleus and cytoplasm of erythroblasts in bone marrow and of the constituent cells of erythroid clones in vitro. The activity in erythrocytes from umbilical cord blood was less than that in corresponding cells from the peripheral circulation of adults. AChE was observed also in human megakaryocytes and in leucocytes at all levels of differentiation, including the components of granulocyte‐macrophage clones. Pseudocholinesterase was detected likewise across the spectrum of erythroid (and leucocyte) ontogeny, suggesting that these enzymes may exercise an important function in hematopoiesis.
Acetylcholinesterase in the human erythron. II. Biochemical assay
Authors: Barr Ronald D. , Koekebakker Marijke , Lawson Alison A.
Published: February 2007

Acetylcholinesterase (AChE) is an integral erythrocyte membrane protein. A role for the enzyme in the developing human erythron is being explored. Assays of AchE by the standard Ellman technique overestimate the amount of enzyme by failing to account for the contribution of hemoglobin to the optical density of the reaction mixture. Furthermore, reliance on substrate selection alone for specificity is unsatisfactory. Incorporation of inhibitors of “true” AchE and of pseudocholinestearase confer greater ability to distinguish one enzyme from the other. In our experience, the inhibitor constant (K1) for edrophonium, which is highly specific for AChE, is approximately 5 × 10−5M against adult human erythrocytes that contain significantly more total cholinesterase activity than do erythrocytes from umbilical cord blood. This consists of both “true” and “pseudo” enzyme, the former predominating and accounting for 0.75–1.65 (mean 1.02, median 0.87) femtomoles of substrate hydrolysed per min per cell in adult blood, with values of 0.15–1.04 (mean 0.71, median 0.73) obtained on cord blood. Moreover, the enzyme activity in neonatal erythrocytes has a rather different inhibitor profile from that of adult cells. AChE was also demonstrated in fresh (ALL) and cultured (K562 and HL60) human leukemic cells, as well as in primitive granulocyte‐macrophage and erythroid cells cloned from normal human bone marrow. In the erythroid colonies the enzyme activity was 0–3.76 (mean 1.20, median 0.76) femtomoles per min per cell, apparently the first successful measurement of AChE in such cells.
T(8;21) With a phenotype of chronic myeloid leukemia
Authors: Raskind Wendy H. , Papayannopoulou Thalia , Hammond William P.
Published: February 2007

A myeloproliferative disorder having the phenotype of chronic myeloid leukemia (CML) with t(8;21) is reported. Neither t(9;22) nor a DNA rearrangement in the bcr region was detected. The presence of t(8;21), in contrast with previous experience, does not appear to prevent full maturation of the granulocytic series.