bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemoglobin constant spring defined by specific oligonucleotide hybridization and hemoglobin D Punjab (β121→Gln) in a Batak Indonesian family
Authors: Kosasih Eddi N. , Cai Shi‐Ping , Kan Yuet W. , Lie‐Injo Luan Eng
Published: February 2007

A Batak Indonesian from North Sumatra with hemoglobin (Hb) D Punjab (α2 β2 121→Gln) and hemoglobin Constant Spring (Hb CoSp) is described. The 24‐year‐old man did not have clinical symptoms, and his hematological indices were normal. However, he had a persistent slight elevation of fetal hemoglobin level. His mother and his brother were heterozygous for Hb D Punjab; his father had Hb CoSp trait. A sister did not have any abnormal hemoglobin. To show the exact molecular defect leading to the synthesis of Hb CoSp in this family, genomic DNA from the father was analyzed by hybridization with synthetic oligonucleotides. Genomic DNA was digested with Sst I and Hind III producing a 1.05‐kb fragment from the 3′ end segment of the α2‐globin gene, including the termination codon. Two nonadecamers were synthesized to serve as probes: one, entirely homologous to the normal 3′ end of α2A‐globin gene sequence, including the termination codon TAA, the other different from it by a replacement of the T in the termination codon TAA with C, changing it to CAA, the codon for the amino acid glutamine. DNA from normal controls gave a positive signal with the normal α2TAA oligonucleotide probe but negative with the α2CAA probe. The father of propositus who had Hb CoSp trait gave a positive signal with the normal α2TAA oligonucleotide probe as well as with the α2CAA oligonucleotide probe, showing him to be heterozygous for the α2CAA‐globin gene. This result shows that the Hb CoSp in the Batak family is indeed due to a replacement of T by C in the TAA termination codon of the α2‐globin gene changing it to CAA the codon for glutamine. This explains the resulting readthrough of the untranslated sequence of the mRNA.
IgD multiple myeloma: A cure at 21 years
Authors: Kyle Robert A.
Published: February 2007

A 52‐year‐old man with a plasmacytoma of the body of T‐10 in February 1965 returned 6 months later with multiple myeloma characterized by bone pain, osteolytic lesions, and IgD λ monoclonal protein in the serum, 6.1 g of Bence Jones protein in the urine, and 21% plasma cells in the bone marrow. The M‐protein and bone pain disappeared within 6 weeks after therapy with melphalan and prednisone was started. Therapy was discontinued in December 1974. Immunoelectrophoreses and immunofixations of the serum and urine over the years revealed no monoclonal protein. A mediastinal tumor developed, and the patient died of respiratory insufficiency on October 23, 1986. Autopsy revealed a large bronchogenic carcinoma of the right lung extending to the mediastinum, trachea, and esophagus. There was no evidence of multiple myeloma. This patient had responded rapidly to chemotherapy and had no recurrence of myeloma during a 21‐year follow‐up.
Antifibrinolytic therapy in the management of the kasabach merritt syndrome
Authors: Ortel Thomas L. , Onorato James J. , Bedrosian Camille L. , Kaufman Russel E.
Published: February 2007

The Kasabach Merritt syndrome consists of thrombocytopenia, microangiopathic he‐molytic anemia, and a localized consumption coagulopathy that develops within the abnormal vascular channels of a hemangioma. In general, these patients demonstrate only mild abnormalities of screening clotting tests, but they can potentially develop life‐threatening complications. We present a patient who developed a severe anemia that was refractory to erythrocyte transfusions. Treatment with epsilon‐aminocaproic acid to inhibit fibrinolysis and cryoprecipitate to replenish his deficient circulating fibrinogen interrupted the cycle of his systemic coagulopathy and enabled us to transfuse him to a normal hematocrit.
Defective release of tissue plasminogen activator in patients with sickle cell anemia
Authors: Phillips George , Mitchell Lanetta B. , Pizzo Salvatore V.
Published: February 2007

Recent studies suggest that intravascular coagulation occurs in sickle cell anemia. There is also some evidence that decreased fibrinolytic activity may be associated with the disorder. In the current study we measured tissue plasminogen activator levels (t‐PA) in seven asymptomatic patients with sickle cell anemia. The mean level of releasable t‐PA was only 0.01 lU/mL ± 0.005 (SEM) as compared to 118 healthy volunteers with levels of 0.70 ± 0.10 (SEM). Despite the small sample size, the difference between the two groups was statistically significant (P < .001). These data suggest that defective release of t‐PA may contribute to a hypercoagulable state in sickle cell anemia.
Evidence for posttranslational control of fetal hemoglobin synthesis
Authors: Qiu C. C. , Abraham E. C.
Published: February 2007

Subunit competition experiments were conducted by recombining various amounts of α‐subunits with an equimolar mixture of γ‐and βA‐subunits. The results showed that γ‐subunits combine with α‐subunits less readily than β‐subunits. Thus, in the presence of α‐chain deficiency (α‐thalassemia) the formation of HbA is preferred over HbF, resulting in a decrease in the level of the latter.
Platelet antibody: Review of detection methods
Authors: Schwartz Kenneth A.
Published: February 2007

The driving force behind development of in vitro methods for platelet antibodies is identification of plasma factors causing platelet destruction. Early methods relied on measurement of platelet activation. Current methods are more specific and use a purified antibody against immunoglobulin or complement, which is usually labeled with 125I or tagged with an enzyme or fluorescein. Comparisons of guantitation of platelet‐associated IgG show wide variability between different methods. The disparate results can be related both to differences in binding of secondary antibodies to immunoglobulin in solution compared to immunoglobulins attached to platelets and to the improper assumption that the binding ratio between the secondary detecting and primary antiplatelet antibody is one. Most assays can 1) identify neonatal isoimmune thrombocytopenia and posttransfusion purpura, 2) help to differentiate between immune and nonimmune thrombocytopenias, 3) help to sort out the offending drug when drug‐induced thrombocytopenia is suspected, and 4) identify platelet alloantibodies and potential platelet donors via a cross match assay for refractory patients. However, the advantages of quantitative assays over qualitative methods with respect to predictions of patients clinical course and response to different treatments remain to be investigated.
Transient ischemic attack in a patient with congenital protein‐c deficiency during treatment with stanozolol
Authors: de Stefano Valerio , Leone Giuseppe , Teofili Luciana , Ferrelli Rita , Pollari Giuseppe , Antonini Vincenzo , Bizzi Bruno
Published: February 2007

A patient with congenital protein‐C deficiency was treated with stanozolol for 8 weeks to increase circulating levels of protein C. A rise in protein C was achieved, accompanied by an increase in factor II, factor X, antithrombin III, and protein S; but at the 8th week the patient suffered a transient ischemia attack.
Probable genetic linkage between genes coding for platelet‐specific antigens of the PIA and bak systems
Authors: Letellier Steven J. , Hunter Jay B. , Aster Richard H.
Published: February 2007

Studies of the inheritance of the platelet‐specific alloantigens PIA1/PlA2 and Baka/Bakb in informative families provided evidence that the genes determining PlA and Bak antigens are in close genetic linkage (P = .004). In 154 normal, unrelated Caucasian subjects it was found that the antigen PIA1 is associated with Baka and the antigen PIA2 with Bakb more often than would be expected by chance (P < .05). Bak and PIA antigens are carried on platelet membrane glycoproteins IIb and IIIa, respectively, which are decreased or absent in the inherited platelet disorder Glazmann's thrombasthenia. Thus, the findings suggest that the defect in this disease involves two closely linked genes.
Testicular tumor as the first manifestation of B‐lymphoid blastic crisis in a case of Ph‐positive chronic myelogenous leukemia
Authors: Ohyashiki Junko H. , Ohyashiki Kazuma , Shimizu Hirofumi , Miki Makoto , Kimura Nobuhiro , Mori Shigeo , Fujisawa Kouji , Akatsuka Jun‐Ichi , Toyama Keisuke
Published: February 2007

We report an 8‐year‐old boy with Ph‐positive chronic myelogenous leukemia (CML) who showed a testicular tumor as the first manifestation of blastic crisis. Pathological examination of the excised testis revealed marked infiltration of immature cells, whereas bone marrow remained in the chronic phase. Immunohistochemical and molecular examinations disclosed the immature cells to have B‐lymphocyte surface determinants and immunoglobulin JH rearrangement. DNA obtained from the testis and peripheral blood cells showed similarly rearranged bcr configurations, indicating that infiltrating cells in the testis originated from the CML clone. Bone marrow showed B‐lymphoid blastic crisis 4 months after testicular involvement.
Daily exposure to forty percent oxygen causes a decrease in platelet count
Authors: Meintjes André F. , Baynes Roy D. , Rogers Geoff G. , Mendelow Barry V.
Published: February 2007

A study was undertaken to evaluate a previous observation made in this laboratory that hyperoxic treadmill training is associated with a decrease in the circulating platelet count (PLT). The subjects studied breathed air containing 40% oxygen for 30 min/day, 5 days/week, for 6 weeks, while at rest in the seated position. Such exposure resulted in a consistent fall in PLT between day 1 and day 5 of each week (P < .01). In addition, there was a progressive decline in PLT over the 6 weeks of exposure to the hyperoxic air, PLT being inversely correlated with the duration of hyperoxic exposure (rs = ‐0.886, P < .02). The total decrease in PLT over the 6 weeks was 56 ± 46 ± 109 I−1 (P < .025). Not surprisingly, these changes were mirrored in the plateletcrit (Pct). The decrease in PLT did not appear to be secondary to either hemodilution or reduced erythropoietic stimulation. The mechanism of production and the biological significance of these changes remain to be elucidated.
Immunogenicity of a recombinant hepatitis B vaccine in hemophiliacs
Authors: Mannucci P. M. , Gringeri A. , Morfini M. , De Biasi R. , Tirindelli M. C. , Tamponi G. , Baudo F. , Carnelli V. , Ciavarella N. , Colombo M. , Zanetti A.
Published: February 2007

Yeast‐recombinant vaccines against hepatitis B virus (HBV) are now available, but there is no information about whether or not they are immunogenic in patients with hemophilia and other congenital bleeding disorders. Twenty micrograms of a recombinant vaccine expressing the adw serotype of the hepatitis B surface antigen (HBsAg) were given to 41 patients negative for HBV markers and again after 1 and 6 months. Ten percent of the vaccinees had anti‐hepatitis B surface antibody (anti‐HBs) responses, with titers of 10 mlU/ml or more, 1 month after the first dose of vaccine. The percentage of anti‐HBs‐positive patients increased to 54% after the second dose and to 98% after the third dose, with only one non‐responder. Hence, the recombinant vaccine was immunogenic, with percentages of seroconversion and anti‐HBs titers similar to those achieved with plasma‐derived vaccines.
Rapid excretion of gallium‐67 isotope in an iron‐overloaded patient receiving high‐dose intravenous deferoxamine
Authors: Baker David L. , Manno Catherine S.
Published: February 2007

A 23 year‐old black male with homozygous sickle cell disease (Hb SS disease) and transfusional iron overload was admitted for evaluation of response to intravenous deferoxamine (DFO) therapy. Soon after admission, the patient suffered an intraventricular hemorrhage and during his subsequent hospitalization developed a persistent fever of undetermined origin (f.u.o.). Included in the diagnostic evaluation of fever was a gallium 67 scan (Ga‐67), which was initially nondiagnostic because of Ga‐67 citrate's preferential chelation by DFO. After DFO was discontinued, a repeat scan demonstrated a lesion above the left kidney.

To our knowledge the unusual interaction in vivo of DFO with Ga‐67 citrate has not been reported in the clinical literature. With the anticipated increased use of chelation therapy for patients with transfusional iron overload, this interaction may be encountered more frequently. DFO should be discontinued before the use of Ga‐67 scanning in this clinical situation, or an alternative isotopic scan, such as indium‐labelled white cells, should be considered.
Coagulation studies in thrombotic thrombocytopenic purpura, with special reference to von willebrand factor and protein S
Authors: Takahashi Hoyu , Tatewaki Wataru , Nakamura Tadao , Hanano Masaharu , Wada Ken , Shibata Akira
Published: February 2007

The profile of blood coagulation and fibrinolysis was studied in detail in eight patients with acute thrombotic thrombocytopenic purpura (TTP). In the majority of the patients, fibrinogen, factor XIII, antithrombin III, α2‐plasmin inhibitor, plasminogen, and α2‐macroglobulin were normal, whereas FDP, plasmin‐α2‐plasmin inhibitor complex, and tissuetype plasminogen activator antigen were marginally or moderately elevated. Low fibronectin values were observed in four patients. Protein C and C4b‐binding protein were nearly normal, whereas total protein S and free protein S were reduced in five and six patients, respectively. A positive correlation was found between total protein S and C4 and between free protein S and C3. von Willebrand factor antigen (vWf:Ag) and ristocetin cofactor (RCof) were either normal or elevated, but RCof/vWf:Ag ratio was decreased in seven patients. Crossed immunoelectrophoresis and sodium dodecyl sulfate (SDS)‐agarose gel electrophoresis revealed that the large vWf multimers were either absent from or relatively decreased in all patients except one. In addition, one patient had unusually large vWf multimers, and a low‐molecular‐weight vWf fragment was apparently observed in three patients. These findings indicate that the intravascular generation of thrombin and plasmin was minimal in TTP and suggest that the alterations of the vWf molecule were caused not only by consumption through its participation in platelet thrombus formation but also by accelerated proteolysis. Low protein S values would be related to the immunological abnormalities underlying TTP.
Severe thrombotic tendency associated with a type I plasminogen deficiency
Authors: Leebeek Frank W. G. , Knot Eduard A. R. , Cate Jan Wouter Ten , Traas Daan W.
Published: February 2007

We report a 45‐year‐old female patient with recurrent spontaneous deep vein thrombosis associated with an isolated hypoplasminogenemia (plasminogen activity and antigen level of 42% and 37%, respectively). The plasminogen molecule was normal as demonstrated by a normal activation by tissue plasminogen activator, electrophoretic mobility on crossed immunoelectrophoresis, molecular weight, and binding to lysine sepharose. All other hemostatic parameters predisposing to recurrent thrombosis were normal. A stimulation test with desmopressin acetate (DDAVP) showed a normal plasma rise of both tissue plasminogen activator and factor VIIIR:WF. This isolated plasminogen deficiency apparently is due to a decreased synthesis of a normal plasminogen molecule and is associated with a severe thrombotic tendency.
Ovarian relapse in a young woman with acute lymphoblastic leukaemia
Authors: Heaton David C. , Duff Gerald B.
Published: February 2007

Bilateral ovarian relapse in a young woman with acute lymphoblastic leukaemia (ALL) was treated by oophorectomy and intensive chemotherapy. She remains well off therapy 97 months following diagnosis and 45 months from ovarian relapse.
Abnormalities in lymphocyte profile and specificity repertoire of patients with Waldenstrom's macroglobulinemia, multiple myeloma, and IgM monoclonal gammopathy of undetermined significance
Authors: Pilarski Linda M. , Andrews E. Joy , Serra Horacio M. , Ledbetter Jeffrey A. , Ruether Bernard A. , Mant Michael J,
Published: February 2007

The characteristics of T and B lymphocyte profile and B lymphocyte specificity repertoire were compared in patients with Waidenstrom's macroglobulinemia (WM), IgM monoclonal gammopathy of undetermined significance (IgM MGUS), multiple myeloma (MM), and age‐matched normal subjects. Patients with MM had both significantly reduced frequency and number of sIg+ (surface Ig) B cells, whereas patients with WM and IgM MGUS had a reduced frequency but normal numbers of sIg+ B cells in circulation as detected in a capping assay. WM was distinguished by the large numbers of cells in the peripheral blood lymphocyte (PBL) pool that expressed CDS (BA‐2) and CD24 (BA‐1) and were monoclonal, based on light chain analysis using flow cytometry. The profile of T lineage cells showed that the ratio of CD4:CD8 was significantly reduced in both MM and WM due to a reduction in the CD4 set. The CD4+ cells were qualitatively abnormal as well, with an enriched proportion of the 4B44 (CDw29) subset and decreased proportion of the Lp220+ (CD45R) subset. This appeared to be an effect of the disease process on the relatively immature Lp220+ set. From clonal analysis, those patients with WM or IgM MGUS (unlike MM patients) did not exhibit enhanced reactivity with auto‐lg determinants, and most WM patients (7/8) and half of the IgM MGUS patients (3/6) did not have enriched proportions of B cells reactive to tetanus toxoid (TT). The TT‐specific B cells in both WM and IgM MGUS, in contrast to MM, appeared fulfy functional in secretion of anti‐TT IgM in vivo. We speculate that the more severe immunodeficiency in MM may be controlled or exacerbated by the presence of an anti‐Ig network. The absence of this network in WM allows a relatively more effective immune response, but the immunodeficency that is observed in these patients involves some abnormality in normal lymphocyte differentiation (is also present in MM).
Studies of the proliferation and differentiation of immature myeloid cells in vitro. I. chronic myelogenous leukemia
Authors: Wang Zique , Gao Xue Zhi , Preisler Harvey D.
Published: February 2007

Immature cells prepared from chronic myelogenous leukemic patients in the chronic or blastic phase of their disease were placed into suspension culture in vitro and studied over a 2‐week period. Regardless of the status of the disease, the immature cells proliferated and maintained good viability. In contrast, evolution of the disease toward blastic crisis was associated with a progressive loss in the ability of the immature cells to differentiate. Cell proliferation and differentiation were independent of added growth factors.
Diffuse panbronchiolitis as a pulmonary complication in patients with adult T‐cell leukemia
Authors: Ono Kazutoshi , Shimamoto Yoshinori , Matsuzaki Miwako , Sano Masayuki , Yamaguchi Tsuneko , Kato Osamu , Yamada Hozumi , Yamaguchi Masaya
Published: February 2007

Forty‐three cases of adult T‐cell leukemia (ATL) admitted to our hospital between 1982 and 1987 were studied. Three of those were found to be complicated with diffuse panbronchiolitis (DPB). The incidence of DPB is considered to be significantly higher in patients with ATL. The three DPB‐complicated cases composed one case each of the smoldering, chronic, and acute type of ATL. In each type, DPB preceded overt ATL and Candida afbicans was found in sputa following detection for bacteria. The DPB complication apparently worsened the prognosis of the ATL patients. We have discussed a possible relationship between ATL and DPB.
Advanced Hodgkin disease (clinical stages IIIB and IV): Low relapse rate after brief chemotherapy followed by high‐dose total lymphoid irradiation
Authors: Colonna P. , Andrieu J. M. , Ghouadni R. , Zouaoui‐Benhadji Z. , Afiane M. , Kubisz P. , Tourani J. M. , Belhadj‐Merzoug K. , Krisch C. , Laugier A.
Published: February 2007

From January 1980 to September 1986, 50 patients with Hodgkin disease, clinical stages (CS) IIIB (26 cases) and IVB (24 cases) were treated by three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, followed by high‐dose (40 Gy) (sub)total lymphoid irradiation, including the spleen. Ten patients (2 CS IIIB, 8 CS IVB) were in failure, and seven (4 CS IIIB, 3 CS IVB) died during their first complete remission (2 from treatment‐related complications, 1 from unknown cause, 4 from insufficient supportive care and/or a shortage of health supplies); three patients (CS IIIB) relapsed (2 alive in second complete remission, 1 deceased). After 7 years, actuarial survival and relapse‐free duration were, respectively, 64% for the 50 patients and 89% for the 40 patients in complete remission. Unfavourable outcome was observed in patients with pelvic nodal involvement. The low relapse rate (none in CS IVB) was the most striking result after brief chemotherapy followed by total lymphoid irradiation.
Splenic irradiation as primary therapy for prolymphocytic leukemia
Authors: Kiss A. , Haubenstock A. , Bognar H. , Scheiderbauer R. , Ai‐Mobarak M. , Base W.
Published: February 2007

A patient with prolymphocytic leukemia (PLL), a lymphoproliferative disorder that carries a poor prognosis, is presented. The disease was diagnosed at an early stage and treatment could be delayed for four years. When massive, painful splenomegaly developed, splenic irradiation (SI) was chosen as the primary form of therapy and an excellent systemic response could be achieved. Our observation is in agreement with preliminary studies, which advocate SI as the primary form of therapy in PLL. Furthermore, it is emphasized that an early diagnosis of PLL is necessary to establish its true course and that the prognosis may be better than originally thought.
Morphologic and cytochemical characteristics of acute promyelocytic leukemia
Authors: Davey F. R. , Davis R. B. , Maccallum J. M. , Nelson D. A. , Mayer R. J. , Ball E. D. , Griffin J. D. , Schiffer C. A. , Bloomfield C. D.
Published: February 2007

The existence of two distinct subtypes of acute promyelocytic leukemia was confirmed and characterized based on morphologic features of leukemic cells in a series of 63 patients studied by the Cancer and Leukemia Group B (CALGB). Seventeen patients (27%) had microgranular leukemic cells (M3V), and 46 patients (73%) had hypergranular leukemic cells (M3). These patient cohorts were studied for other laboratory and clinical features. Leukemic cells from M3V patients stained less frequently than leukemic cells from M3 patients for myeloperoxidase (median, 93% vs. 99%; P=.006), periodic acid‐Schiff (median, 57% vs. 92%; P=.0001), ASD‐chloroacetate esterase (median, 45% vs. 87%; P<.0001), and alpha‐naphthyl acetate esterase (0% vs. 37%; P=.003). Patients with M3V had a higher platelet count (median, 50 vs. 30 × 109/L; P=.01) and tended to have a higher leukocyte count (median, 7.4 vs. 2.2 × 109/L; P=.06) than M3 patients. The patients with M3V morphology were more likely to be nonwhite (29% vs. 7%; P=.03), female (71% vs. 37%; P=.02), and to be infected at the time of presentation (71% vs. 35%; P=.02). No differences in the frequency of the t(15;17) karyotype or the immunopheno‐typic expression of the leukemic cells were noted in the two morphologic subtypes of acute promyelocytic leukemia. Fewer patients with M3V tended to enter complete remission (65% vs. 80%; P=.20), but no significant differences were found in the duration of complete remission (P=.81; 1 year rate, 50% vs. 85%), or probability of survival (P=.67; 1 year rate, 49% vs. 68%).
Reversal of bone marrow fibrosis and subsequent development of polycythemia in patients with myeloproliferative disorders
Authors: Talarico Lilia , Wolf Barbara C. , Kumar Aruna , Weintraub Lewis R.
Published: February 2007

Bone marrow fibrosis is a characteristic finding in agnogenic myeloid metaplasia and in the spent phase of polycythemia vera. It is commonly believed that the reticulin deposition is irreversible. However, we report four patients who demonstrated clinical and laboratory evidence of transition from myelofibrosis to polycythemia. The transition was documented by improvement in the hemoglobin concentration and by determination of the Cr51 red blood cell mass, accompanied by a resolution of the fibrosis on serial bone marrow biopsies. Two of the patients had been treated with alkylating agents and splenectomy, one with myelosuppressive therapy without splenectomy, and one with splenectomy alone. These findings indicate that bone marrow fibrosis in the chronic myeloproliferative disorders is not always an irreversible phenomenon. Pathogenetic implications will be discussed.
Cyclosporin A in the treatment of severe aplastic anemia: Description of a case complicated by the development of tubercular pericarditis during treatment
Authors: Pogliani E. M. , Cortellaro M. , Foa P. , Lurlo A. , Polli E. E.
Published: February 2007

We report on a 62 year‐old woman who developed a severe aplastic anemia requiring frequent packed red cell and platelet transfusions. Since conventional pharmacological therapy was ineffective, treatment with Cyclosporin A was started, resulting in a significant increase of leukocyte, platelet, and red cell counts. However, 5 months after the beginning of Cyclosporin A treatment, despite a past medical history not significant for clinical tuberculosis, the patient developed tubercular pericarditis. This report underlines the need for a careful follow‐up of Cyclosporin A‐treated patients aimed at a prompt diagnosis of possible infectious complications.
Ring‐shaped nuclei in human neutrophilic leukocytes of healthy individuals: Evidence of their occurrence and characteristics
Authors: Cabral Humberto R. A. , Robert Gabriela B.
Published: February 2007

In our previous work we found the presence of ring‐shaped nuclei in circulating neutrophils of healthy individuals whose nuclei were stained only by means of the Feulgen reaction [1]. In our present work, we performed another study on the blood of 52 healthy human donors and stained their blood films with hematoxylin. In all cases, ring‐shaped nuclei were revealed. In this series, the number of this type of nuclei was high: 15.61% ± SD 7.18%. The ring nuclei of healthy humans had thin segments, such as we had previously found by means of Feulgen method.
Reversible agranulocytosis related to azidothymidine therapy
Authors: Goldsmith Jonathan C. , Irvine Wendy
Published: February 2007

Hematopoietic toxicity from Zidovudine (AZT) is fairly common, resulting in a requirement for red cell transfusions in up to 25% of patients. Reversible agranulocytosis occurred following approximately 1 week of AZT therapy in a man with AIDS. He recovered from the episode without incident. There was no evidence for underlying bone marrow dysfunction or an adverse drug reaction. Careful monitoring of AZT therapy continues to be of great importance.
In vitro DNA synthesis by megaloblastic bone marrow: Effect of folates and cobalamins on thymidine incorporation and de novo thymidylate synthesis
Authors: Das Kshitish C. , Herbert Victor
Published: February 2007

The de novo pathway of thymidylate synthesis (i.e., methylation of dUMP to dTMP) is directly folate dependent and indirectly vitamin B12 (cobalamins) dependent. In deficiency of these vitamins, this pathway is impaired, and exogenous deoxyuridine (dU) fails to suppress adequately in vitro incorporation of [3H]thymidine (3H‐TdR) into DNA via the salvage pathway (i.e., abnormal dU suppression). This abnormality is corrected by the addition of folate compounds (analogues) and/or vitamin B12 depending on the nature of the underlying deficiency. We studied the effects of addition of PteGlu, 5‐methyl THF (5‐CH3‐FH4), 5‐formyl‐THF (5‐CHO‐FH4), and hydroxy‐cobalamin (OH‐cbl) on 3H‐TdR incorporation into DNA and thymidine kinase activity (salvage pathway), and on [3H]deoxyuridine (3H‐dU) incorporation and dU suppression values (de novo pathway) in cultures of normal and megaloblastic bone marrows. The results showed that 3H‐TdR incorporation into DNA and the salvage enzyme, thymidine kinase, activity were greater and 3H‐dU incorporation into DNA less in megaloblastic cells as compared with normal cells. The addition of folates significantly reduced 3H‐TdR incorporation and thymidine kinase activity and enhanced 3H‐dU incorporation in folate and vitamin B12‐deficient cells except that 5‐CH3‐FH4 had no effect on vitamin B12‐deficient cells. None of these additives had any significant effect on normal cells. This study also showed that the addition of the deficient vitamin(s) to the “control tubes” in the dU suppression test is inappropriate, as these vitamins may at least partially correct the defect in cellular DNA synthesis caused by the deficiences of these vitamins and may mask these deficiencies in the results of the in vitro correction of the dU suppression abnormalities in mild cases of megaloblastic anemia.
Characterization of von willebrand factor in factor VIII concentrates
Authors: Fricke William A. , Yu Mei‐Ying Wong
Published: February 2007

Commercial concentrates of factor VIII (FVIII) were analyzed in order to 1) determine the effects of viral inactivation on von Willebrand factor (vWF); 2) evaluate the vWF content of the new, immunopurified concentrates; and 3) assess their potential for correcting the long bleeding time of von Willebrand disease (vWD). Included in our study were products that had been treated to inactivate viruses; older, untreated products; and the new, immunopurified concentrates. We measured von Willebrand factor antigen (vWF:Ag), ristocetin cofactor activity (RCoF), and vWF multimeric and subunit composition. A newly developed radioimmunoassay (RIA) was used to quantitate vWF:Ag. The vWF:Ag content varied from 0.083 μg/IU FVIII:C for Hemofil M to 32.2 μg/IU FVIII:C for Humate‐P, whereas pooled normal human plasma (NHP) contained 6.3 μg/IU FVIII:C. The RCoF varied from 0.0007 to 2.09 U/IU FVIII:C, with the immunopurified concentrates having the lowest values and Humate‐P the highest. The ratio of RCoF to vWF:Ag ranged from 11 to 96 U/mg, as compared to a ratio of 160 for NHP. All of the concentrates lacked the largest vWF multimers, and all had abnormal triplet patterns. Modest differences between some untreated concentrates and their treated counterparts were noted. As expected, the immunopurified concentrates had much lower levels of all vWF activities than the conventionally prepared products. Our data suggest that none of the concentrates have as great a capacity as NHP to correct the prolonged bleeding time of von Willebrand disease.
Pituitary abscess after autologous bone marrow transplantation
Authors: Leff Richard S. , Martino Roy L. , Pollock W. James , Knight William A.
Published: February 2007

The first case of pituitary abscess arising in a patient during recovery from autologous bone marrow transplantation is reported. A 31‐year‐old man with a 9 month history of T‐cell lymphoma died suddenly more than 60 days after successful treatment with high‐dose cyclophosphamide, total body irradiation, and autologous bone marrow infusion. Autopsy revealed a pituitary abscess associated with clinically silent sphenoid sinusitis. Unique aspects of this case are presented and clinical and pathologic features of pituitary abscess are reviewed. Although rare, pituitary abscess may complicate recovery from bone marrow transplantation.
Age‐dependent variation in the cytosol/membrane distribution of red cell protein kinase‐C
Authors: Ramachandran M. , Abraham E. C.
Published: February 2007

An age‐dependent increase in membrane association of protein kinase‐c and a decrease in the cytosolic enzyme, especially in the densest fraction rich in sensescent red cells was observed in Stractan‐gradient‐separated normal erythrocytes.
Controlled prospective study of factor IX concentrate therapy and immunodeficiency
Authors: Hultin Mae B. , Dattwyler Raymond J. , Lipton Richard A.
Published: February 2007

In 1983, six patients who were exclusively treated with factor IX (FIX) concentrate (>40,000 units/yr) were prospectively matched for age and dosage to six patients treated exclusively with factor VIII (FVIII) concentrate and to six normal male controls. At baseline evaluation between October 1983 and May 1984, both groups had significantly decreased absolute T helper cell counts (mean of 452/μl and 505/μl for FIX‐ and FVIII‐treated groups, respectively) compared to normal (1,157/μl). By August 1988, three of the six FIX‐treated group have developed AIDS and two are seropositive for antibody to the human immunodeficiency virus (HIV). Four of the six FVIII‐treated group have HIV seropositivity or disease. The other three patients (1/6 for FIX and 2/6 for FVIII) declined HIV antibody testing. Our results support other studies showing a dose‐related risk of HIV exposure for FIX concentrate‐treated patients and do not support the view that FIX concentrate was intrinsically safer than FVIII concentrate.
Relative iron deficiency in hereditary spherocytosis
Authors: Zanella A. , Barosi G. , Berzuini A. , Colombo M. B. , Quaglini S. , Volpes D. , Sirchia G.
Published: February 2007

Seventy‐three patients with hereditary spherocytosis (HS) (58 nonsplenectomized, 15 splenectomized) were studied to evaluate iron status and the adequacy of iron availability for erythropoiesis. Splenectomized patients, who had hemoglobin levels in the normal or upper normal range, had higher levels of serum iron, transferrin saturation, and serum ferritin than normal matched controls and normal zinc protoporphyrin (ZnPP) levels. On the contrary, nonsplenectomized patients presenting with mild to severe anemia had higher red cell ZnPP concentrations than both splenectomized subjects and matched normal controls. ZnPP in nonsplenectomized patients correlated inversely with Hb concentration, mean corpuscular volume (MCV), mean red cell hemoglobin concentration (MCHC), transferrin saturation, and serum iron, and directly with reticulocyte count. At multiple regression analysis only Hb concentration was a significant explanatory variable for high ZnPP. The authors conclude that a number of nonsplenectomized HS patients have relative iron deficiency primarily because of expansion of erythropoiesis caused by anemia.
Net renal tubular reabsorption of zinc in healthy man and impaired handling in sickle cell anemia
Authors: Yuzbasiyan‐Gurkan Vilma A. , Brewer George J. , Vander Arthur J. , Guenther Michael J. , Prasad Ananda S.
Published: February 2007

Zinc deficiency is a significant clinical finding in sickle cell anemia (SCA) and abnormalities of zinc handling such as hyperzincuria are present. The cause of increased urinary zinc excretion in SCA is not clear. To define the renal handling of zinc in SCA and in healthy subjects, we measured zinc (total and ultrafilterable plasma zinc, urine zinc) and creatinine clearance in eight healthy and seven SCA subjects. Ultrafilterable zinc in plasma was assessed by equilibration of plasma with 65Zn followed by filtration through Amicon Cetriflo CF25 cones. While the mean filtered load of zinc was not significantly different between the two groups, the mean zinc excretion rate was approximately threefold higher in patients (1.73 ± 0.96 vs. 0.63 ± 0.39 μg/min, P<.05). In controls, zinc excreted was significantly less than zinc filtered (P<.005), the fractional excretion of zinc averaging 0.49 ± 0.31, indicating net reabsorption. This was not the case for the SCA patients. We conclude that there is impaired renal tubular handling of zinc in SCA.
Frequency of congenital anomalies in patients with histiocytosis X
Authors: Sheils Catherine , Dover George J.
Published: February 2007

The frequency of congenital anomalies in 39 cases of histiocytosis × collected over a 30 year period was 23%. Through a retrospective chart review of these cases and two control populations (children with bone tumors and children with suspected child abuse) we sought to assess the significance of this finding as well as any special characteristics of those histiocytic patients who had congenital anomalies. The frequency of congenital anomalies in the histiocytosis × group (23%) was greater than the frequency found in our control groups, the bone tumor group (13%), and the child advocacy control group (15%). Considering only major congenital anomalies, the histiocytic population had an increased frequency (18%) relative to both control groups (3% and 8%, respectively). Only one patient with unifocal eosinophilic granuloma had congenital anomalies. Patients with histiocytosis × and congenital anomalies were more likely to have histiocytosis X involving organ dysfunction (lung, liver, hematopoietic). Through this retrospective study we observe an increased frequency of congenital anomalies in patients with histiocytosis X. This observation does not seem to apply to patients with unifocal eosinophilic granuloma. The presence of congenital anomalies, especially multiple congenital anomalies, seemed to be a prognostic indicator of organ dysfunction in our histiocytic population.
Myelodysplastic syndrome with trisomy 11 associated with polycythemia vera
Authors: Ohyashiki Kazuma , Nagasu Masaya , Hojo Hitoshi , Iwabuchi Atsuhiro , Ohyashiki Junko H. , Toyama Keisuke
Published: February 2007

A 52‐year‐old male with myelodysplastic syndrome (MDS) who had a prior history of polycythemia vera is reported. Chromosome analysis revealed that the bone marrow and blood cells at the MDS phase contained trisomy of chromosome 11 as the sole cytogenetic change. Trisomy 11 is rarely found in hematologic neoplasia, and all of the reported cases with trisomy 11 were diagnosed as having nonlymphocytic neoplasia. In this report, a correlation between the chromosome change and leukemia/MDS developed in polycythemia vera is discussed.
Acute nonlymphocytic leukemia with basophilic differentiation and t(9,11)(p22,q23) in a child
Authors: Kubota Masaru , Akiyama Yuichi , Tabata Yasuyuki , Yoshigi Masaaki , Mikawa Haruki
Published: February 2007

A 20‐month‐old child was treated for acute nonlymphocytic leukemia (ANLL) with basophilic differentiation. His leukemic cells also had the cytogenetic abnormality of t(9,11)(p22,q23). Although immature blasts responded well to induction therapy with etoposide, the leukemic cells that were more differentiated toward basophils were quite refractory to the drug. However, complete remission was finally achieved with a conventional multidrug regimen.
Arachidonic acid metabolites produced by platelet‐depleted human blood monocytes: A possible role in thrombogenesis
Authors: Jones C. Michael , Hall Elizabeth R. , Hester Jeanne P. , Wu Kenneth K.
Published: February 2007

The arachidonic acid metabolites produced by human peripheral blood monocytes were studied to determine which metabolites could have a role in thrombogenesis. Monocytes were found to be free of platelets by scanning electron microscopy and by measurement of 12‐HETE. Human peripheral blood monocytes produce thromboxane as their major metabolite. Thromboxane levels reached a plateau at 12–16 hours of culture. Monocytes produced relatively little prostaglandin E2 or F2. In contrast to our control platelet preparation, neither A23187 (1–10 μM) nor exogenous arachidonic acid (0–40 μM) caused an increase in monocyte thromboxane B2. On the other hand, lipopolysaccharide (20 μg per ml), collagen (2.5 mg per 107 cells), and thrombin (5–10 units per ml) caused a two‐ to fivefold increase in monocyte thromboxane B2 in most donors but had no effect on prostaglandin F1α levels. Blockage of thromboxane synthase by 1‐benzylimidazole abolished thromboxane B2 production but did not increase prostaglandin F1α. Finally, aspirin‐treated platelets from a volunteer donor, which were refractory to 30 μM arachidonate, could be aggregated by isolated blood monocytes.

Our data indicate that monocytes are capable of producing thromboxane in large amounts. The regulation of this increase, however, appears to be quite different from platelets. We postulate that monocytes may have a role in hemostasis by virtue of their ability to adhere at sites of vascular injury and release thromboxane, which may enhance platelet aggregation and thrombus formation.
Neutrophil maturation and hypersegmentation promoted in normal bone marrow by a carcinoma‐elaborated protein factor
Authors: Bailey Steven C. , Head Jonathan F. , Greengard Olga
Published: February 2007

In rats with subcutaneously transplanted mammary carcinoma 5A (MC) and 2 to 10‐fold elevations in the blood content of mature neutrophils, 30–50% of the neutrophils showed pronounced hypersegmentation. This phenomenon could be reproduced in liquid culture of bone marrow cells from normal (tumor‐free) animals by 48 hr incubation with the MC host's serum, or with MC‐conditioned medium whose activity was attributable to an over 50,000 MW protein. The effects in vitro, occurring without change in total cell number and accompanied by increases in γ‐glutamyltranspeptidase (GGT) and alkaline phosphatase (AP) activity, included decreases in the percents of progenitors (myeloblasts, promyelocytes, myelocytes, metamyelocytes and bands) and an increase in mature neutrophils 50% of which exhibited obvious hypersegmentation. Much less if any neutrophil hypersegmentation, and no statistically significant decrease in immature cells, occurred in response to the several colony stimulating factors (CSFs) tested, although (in addition to inducing GGT and AP) some CSFs did cause an increase in mature neutrophils.

These investigations demonstrate the efficacy of a MC‐elaborated blood‐borne protein to promote myeloid cell maturation, and describe a system for the first time in which neutrophil hypersegmentation can be studied in vitro.
Large granular lymphocytes from B‐chronic lymphocytic leukemia patients inhibit normal B cell proliferation
Authors: Perri Robert T. , Kay Neil E.
Published: February 2007

Large granular lymphocytes (LGL) may exert regulatory influences on B cell immuno‐globulin synthesis. We, therefore, investigated the influence of LGL from controls and B cell chronic lymphocytic leukemia patients (B‐CLL) on control B cell proliferation to costimulation with the F(ab′)2 fragment of goat antihuman μ and B cell growth factor (BCGF). Purified LGL (>90% by morphology) from control and B‐CLL peripheral blood were added in various concentrations to purified control B cells and incubated with anti‐μ, and BCGF for 3 days. [3H]‐thymidine uptake of B cells was then measured. There was no proliferation of control or CLL LGL alone to the costimulatory signals of the F(ab′)2 fragments of goat antihuman μ chain and BCGF. Addition of control LGL to equal numbers of control B cells did not blunt control B cell responsiveness to BCGF (with control LGL 8,649±298 cpm vs. control B cells alone 8,336 ± 556 cpm, mean ± SEM). When control LGL were increased to 10:1 LGL:B cell ratio, the maximal inhibition by control LGL of control B cell proliferative response to BCGF was 23%. In contrast, addition of CLL LGL at a 1:1 LGL:B cell ratio resulted in marked impairment of the control B cell proliferative response to BCGF (with CLL LGL 3,586 ± 954 cpm vs. control B cells alone 8,649 ± 298 cpm). Inhibition by CLL LGL occurred in a cell‐concentration‐dependent manner. No difference in CLL LGL's inhibitory effect on either resting or activated control B cell responsiveness to BCGF was noted. Inhibition of de novo protein synthesis (by cycloheximide inhibition) of CLL LGL did impair CLL LGL's inhibitory capacity for BCGF‐induced B cell proliferation. A possible explanation for these findings includes the possibility that a subgroup of LGL with B cell suppressive activity may have expanded as a host response to the B cell leukemia or as part of the disordered cell regulation in B‐CLL.
Evaluation of the clinical utility of platelet aggregation studies
Authors: Remaley Alan T. , Kennedy Julia M. , Laposata Michael
Published: February 2007

To determine the diagnostic importance of platelet aggregation studies, we evaluated the clinical utility of these assays by a retrospective review of 188 adult patients initially studied for bleeding abnormalities with platelet aggregation tests at a tertiary care hospital from 1984 to 1987. The primary indications for requesting the tests in our patient population were for the evaluation of a positive bleeding history or abnormal bleeding time (68%), hypercoagulability (17%), thrombocytosis (9%), or a family history of a bleeding disorder (6%). There was a statistically higher incidence of platelet aggregation test abnormalities in patients with highly abnormal bleeding times (40%), in patients with thrombocytosis from myeloproliferative disorders (65%), and in patients with a family history of a bleeding disorder (58%), compared to the other groups studied (16–29%). Of the 64 platelet aggregation tests performed that were abnormal, the following abnormalities were identified: 19 aspirin‐like defects (poor response to arachidonate and decreased second wave responses to weak agonists), which were presumably drug‐induced, ten myeloproliferative‐type disorder defects (abnormal response to epinephrine predominantly) in patients known to have myeloproliferative disease, 34 abnormal patterns not characterized as aspirin or myeloproliferative disorder related, four of which ultimately led to a diagnosis of storage pool disease, and one spontaneous aggregation defect. Our results suggest that platelet aggregation tests rarely lead to the diagnosis of a specific, previously undiagnosed platelet function disorder. Specific recommendations are given for efficient utilization of platelet aggregation tests.
BSF‐2/IL‐6 does not augment lg secretion but stimulates proliferation in myeloma cells
Authors: Tanabe Osamu , Kawano Michio , Tanaka Hideo , Iwato Koji , Asaoku Hideki , Ishikawa Hideaki , Nobuyoshi Masaharu , Hirano Toshio , Kishimoto Tadamitsu , Kuramoto Atsushi
Published: February 2007

Human myeloma cells were highly purified from bone marrow aspirates of 21 patients with advanced immunoglobulin G (IgG)‐type multiple myeloma. B‐cell stimulatory factor 2 (BSF‐2)/interleukin‐6 (IL‐6) was originally characterized as a cytokine that can enhance immunoglobulin secretion from activated normal B cells and increase the expression of secretory‐type Ig mRNA in these B cells, but that does not augment proliferation of activated B cells. However, recombinant IL‐6 (rIL‐6) could not enhance M‐protein (IgG) secretion in freshly isolated myeloma cells in vitro but could augment proliferation of myeloma cells, although myeloma cells constitutively expressed IL‐6 receptors. Furthermore, expression of secretory‐type IgG (γ‐chain) mRNA in myeloma cells was not changed in the presence of IL‐6. These results show that IL‐6 is not an enhancing factor in Ig secretion from myeloma cells, and thus signal transduction through IL‐6 in myeloma cells may be altered as opposed to activated B cells.