bluuebunny/crossref_metadata_2025 huggingface dataset:
Results of induction therapy with vincristine and prednisone alone in adult acute lymphoblastic leukemia: Report of 43 patients and review of the literature
Authors: Hess Charles E. , Zirkle John W.
Published: February 2007

The complete remission (CR) rate in children with acute lymphoblastic leukemia (ALL) who received vincristine (VCR) plus prednisone (PRED) alone for induction is > 90%, and has not improved with the use of more intensive regimens. In adults with ALL, using the same regimen, a CR rate of only 50% is frequently quoted, and is apparently based mainly on unpublished data on only 13 patients from an early Acute Leukemia Group B protocol. We reviewed the case records of 43 adults with previously untreated ALL seen between July 1, 1966 and December 31, 1978 who received VCR + PRED alone for induction. A CR rate of 66% was achieved and compares to an overall figure of 61% from 162 patients collected from the literature. The CR rate was age dependent with 21/29 (76%) < 50 years of age achieving a CR compared to 4/19 (29%) who were < 50 years of age (P < 0.02). The median duration of CR was 8.3 months. For those who achieved a CR, the median survival was 19 months compared to five months for those who either failed to achieve a CR or who achieved only a partial remission (P = 0.004). All patients who achieved a CR received maintenance therapy, and approximately one‐half also received CNS prophylaxis with intrathecal methotrexate. The incidence of isolated CNS relapse was 11% in those who received CNS prophylaxis compared to 20% in those who did not.

From these data and a review of the literature, we conclude that approximately two‐thirds of adults with ALL will achieve a CR with the use of VCR + PRED alone. The median duration of CR, however, is < one year and the median survival is approximately two years. Whether the use of more intensive induction, consolidation, and maintenance regimens will improve these results remains to be established.
Inhibitory effect of short‐chain aliphatic acids on deoxythymidine incorporation into DMA in mitogen‐stimulated and leukemic lymphocytes
Authors: Stolc Viktor
Published: February 2007

The effect of short‐chain aliphatic acids on [3H]deoxythymidine incorporation into DNA was studied in human mitogen‐stimulated lymphocytes. Butyric acid at 1‐‐2 mM level was strongly inhibitory; however, its hydroxy or amino derivatives were ineffective. Valeric and propionic acids were less inhibitory. Formic, acetic, and hexanoic acids did not have any inhibitory effect. The effect of butyrate persisted in washed lymphocytes for 24‐‐48 hr depending on the concentration used and the time of its addition into the incubation medium. The inhibitory effects of butyrate, valerate, and propionate on deoxythymidine and amino acid incorporation into DNA and protein were also found in human leukocytes in myelocytic and lymphocytic leukemias.
Exposure to phorbol diester (TPA) in vitro as an aid in the classification of blasts in human myelogenous and lymphoid leukemias: In vitro differentiation, growth patterns, and ultrastructural observations
Authors: Polliack Aaron , Leizerowitz Rachael , Korkesh Aviva , Gurfel Dorit , Gamliel Haim , Galili Uri
Published: February 2007

Leukemic cells from the peripheral blood of 52 patients with acute and chronic leukemias were incubated with 12‐0‐tetradecanoyl phorbol ester (TPA). Thirty‐one cases of lymphocytic leukemia (18 cases of acute lymphoblastic and 13 cases of chronic lymphocytic leukemia), 13 cases of acute nonlymphoblastic (myelo or myelomonoblastic) leukemia, and eight cases of blastic crisis of CGL (seven cases of predominantly myeloblastic crisis, and one case of lymphoblastic crisis) were studied. In all cases of lymphoid leukemia, cells formed clumps or aggregates after exposure to TPA, while in all cases of myeloid leukemia cells became adherent to the substrate. Seven of the eight cases of blastic crisis of CGL were predominantly myeloid in type and cells adhered to the substrate, while in a single case of lymphoid crisis in CGL cells formed clumps after TPA exposure. Functional, cytochemical, and ultrastructural studies showed altered cell differentiation and continuing in vitro maturation of leukemic cells after exposure to TPA. In the light of the above results, it is concluded that this simple test employing TPA exposure in vitro serves as a reliable means of distinguishing blasts from different origins in human leukemias.
Effects of divalent cations on the conversion of fibrinogen to fibrin and fibrin polymerization
Authors: Kanaide Hideo , Uranishi Takako , Nakamura Motoomi
Published: February 2007

Effects of divalent cations on fibrinogen and its reaction with thrombin were re‐examined and correlated to improve definition of mechanisms underlying the acceleration of clot formation by the ions. The rate of release of fibrinopeptides from fibrinogen was not affected by any of the specific ions studied, but increased rates of fibrin monomer polymerization were obtained with all but magnesium ions. Maximal acceleration of monomer polymerization was observed with the divalent ions at concentration of 2.5–5 mM, and no added specific ion effects were observed with much higher levels. The acceleratory ions were found to have a corresponding effect on the solubility of fibrinogen, as judged from acceleration of its precipitation at low temperature. Although magnesium ions had no effect on fibrin monomer polymerization, they did have a low ranking effect on cryoprecipitation. These data confirm that the principal effect of divalent cations in the fibrinogen‐fibrin transformation is to accelerate fibrin monomer polymerization, and suggest that the acceleration is associated with effects on the solubility of fibrinogen.
Studies of a patient with recurring thrombotic thrombocytopenic purpura
Authors: Kitchens Craig S.
Published: February 2007

A young woman with recurring bouts of thrombotic thrombocytopenic purpura presented an opportunity to study a single patient serially and in depth. This patient underwent 12 remissions in response to fresh frozen plasma, and as little as 250 ml of plasma or plasma from which cryoprecipitate had been extracted was efficacious. Neither the Lian factor nor alterations in either cold‐insoluble globulin or protein C could be demonstrated. Evidence in support of the concept of “exhausted” platelets was generated, in that immediately before a thrombocytopenic relapse, platelet function was altered as manifested by bruising, prolongation of the bleeding time, and decreased platelet aggregation. The in vitro addition of normal plasma to such platelets did not improve aggregation. The antiplatelet agent sulfinpyrazone did not seem to add efficacy. Serial observations support the hypothesis that the progression of pathophysiologic events in this patient is: exhausted platelets, thrombocytopenia, hemolysis, renal perturbations, and central nervous system dysfunction.
Nonsecretory multiple myeloma
Authors: Dreicer Robert , Alexanian Raymond
Published: February 2007

The clinical features and disease course of 29 consecutive multiple myeloma patients without monoclonal globulins are described. This variant accounted for 4.7% of all patients with this disease referred over a 17 year time span. Despite bone marrow plasmacytosis and multiple bone lesions in all, hemoglobin levels were less frequently depressed and immunoglobulin values more frequently preserved in comparison with typical myeloma patients. A low tumor mass was defined in 69%, in comparison with 24% of those with evidence of myeloma protein production. Such earlier disease contributed to the long median survival of 39 months in these patients, a duration about 1 year longer than that of typical patients.
Enzyme alterations in leukemic cells
Authors: Dunn Nancy L. , Maurer Harold M.
Published: February 2007

Recently, much attention has been focused on various enzyme alterations found in leukemic cells. Most of the data generated thus far has involved the study of terminal deoxynucleotidyl transferase, the purine pathway enzymes, and hexosaminidase and other lysosomal enzymes. Differences in both total enzyme activities and isoenzyme patterns have been found to occur among the various leukemia types and subtypes. These changes may prove to be useful aids in diagnosing, classifying, detecting subclinical recurrent or residual disease, and as therapeutic determinants in hematopoietic neoplasia, especially in the lymphoid malignancies.
Familial and constitutional bleeding disorder due to platelet cyclo‐oxygenase deficiency
Authors: Horellou M. H. , Lecompte T. , Lecrubier C. , Fouque F. , Chignard M. , Conard J. , Vargaftig B. B. , Dray F. , Samama M.
Published: February 2007

Three family members from two successive generations had a bleeding tendency. Their template bleeding time was prolonged and platelet aggregation induced by ADP and adrenaline showed no second wave; collagen at low to moderate concentrations failed to aggregate and release ATP, whereas higher amounts aggregated and released. Aggregation and release due to thrombin, ristocetin, and synthetic epoxy derivatives (U 44069 and U 46619) were normal. Arachidonate (AA) was inactive, and was not converted either in thromboxane (TX) A2activity evaluated on the rabbit aorta strip, nor in TXB2evaluated by radioimmunoassay and by radiochromatography. The parallel impairment of TXB2and PGE2formation by the patient's platelets are compatible with a platelet cyclo‐oxygenase deficiency. This study suggests that transmission is autosomal dominant. and confirms that cyclo‐oxygenase is not needed for aggregation and ATP release by high amounts of collagen.
Beta‐thromboglobulin and platelet‐factor 4 in patients with cancer: Correlation with the stage of disease and the effect of chemotherapy
Authors: Al‐Mondhiry Hamid
Published: February 2007

Plasma level of beta‐thromboglobulin (BTG) and platelet factor 4 (PF4), two platelet‐specific proteins, were measured in 20 patients with cancer. None of the patients had evidence of thromboembolism or impaired renal function, and none was taking drugs known to interfere with platelet function. In ten patients who were in complete remission or whose disease was thought to be inactive, the levels of both proteins were essentially within normal limits. The other ten patients had active or progressive symptomatic disease. BTG level was elevated in all but one patient, and PF4 was raised in two patients. These results suggest that in patients with clinically active cancer, a state of ongoing in vivo platelet activation may be present, a phenomenon which may contribute to the known increased occurrence of thromboembolism in patients with malignancy. The intravenous administration of various cytotoxic drugs used in cancer chemotherapy produced no immediate measurable changes in BTG and PF4 level.
A family of hereditary stomatocytosis associated with normal level of Na+‐K+‐ATPase activity of red blood cells
Authors: Mutoh Shigeaki , Sasaki Ryuhei , Takaku Fumimaro , Aoyama Masako , Moriyama Shinichi , Yoshimoto Masahiro , Yawata Yoshihito
Published: February 2007

A rare familial case of hereditary stomatocytosis with hemolytic anemia, increased auto‐hemolysis, increased osmotic fragility, and shortened erythrocyte survival is described. The erythrocytes were abnormally permeable to sodium and potassium. In addition, “Na‐K pump” rate of the red blood cells was increased, while Na+‐K−‐ATPase, Mg2+‐ATPase and Mg2+‐Ca2+‐ATPase activities were within normal limits. Splenectomy induced marked improvement of anemia.
The occurrence of different levels of Gγ chain and of the AγT variant of fetal hemoglobin in newborn babies from several countries
Authors: Huisman T. H. J. , Reese A. L. , Gardiner M. B. , Wilson J. B. , Lam H. , Reynolds A. , Nagle S. , Trowell P. , Yi‐tao Zeng , Shu‐zheng Huang , Sukumaran P. K. , Miwa S. , Efremov G. D. , Petkov G. , Sciarratta G. V. , Sansone G.
Published: February 2007

The γ chain compositions of the fetal hemoglobins of 2453 newborn babies from East Asian countries (1350 babies), from Italy, Yugoslavia, Bulgaria, and Georgia (417 Caucasian babies), and 686 black babies from Georgia were determined by high pressure liquid chromatography. Unusual results for a limited number of babies were confirmed by chemical analyses, and were evaluated further by family studies.

Statistical analyses indicated high gene frequencies for the AγT chain in Italian (f = 0.237), Yugoslavian and Bulgarian (f = 0.238), and white Georgia babies (f = 0.224), a lower frequency in Japan (f = 0.178), and India (f = 0.173), and particularly in mainland China (f = 0.079). The AγT gene frequency in normal (AA) Black babies was 0.102. When a βS or βC mutation was also present this frequency was greatly decreased, particularly in babies with the AC condition (f = 0.036). These results suggest the near absence of the AγT mutation on the chromosome also carrying the βC determinant.

Most babies had the expected Gγ values which vary between 60 and 80%, but several (mainly black) babies had higher values (between 80 and 90%), while one normal black baby had a Gγ value of (nearly) 100%. This condition may be a form of Aγ+1‐thalassemia and has been discussed in detail elsewhere (Blood 58:491‐500, 1981). Thirty‐five clinically normal (mainly Chinese, Indian, and Japanese) babies had Gγ values of about 40%. Twenty‐six babies had Aγ1 values of about 60%, while the remaining nine babies had AγT and AγI chains in a ratio of either 1 to 2 or 1 to 1. Two additional newborns did not produce any Gγ chains, but had only AγI chains or AγI chains. Family studies failed to indicate a specific hematological abnormality. These unusual ratios between the Gγ and (either AγI or AγT) chains have led to speculations regarding possible genetic abnormalities present in these infants.
Altered Immunoregulation in Waldenström's macroglobulinemia. I. The absence of con A‐induced and spontaneous T suppressor cell activity in a patient and his kindred
Authors: Keller Robert H. , Feldman Eric , Libnoch Joseph A.
Published: February 2007

In vitro lymphocyte functions in a patient with Waldenström's macroglobulinemia and his kindred were examined. The percentage and number of total peripheral blood T cells and the absolute number of FCγ bearing T cells were decreased in the patient and family members compared to controls but the B cells and monocytes were normal. In addition, PHA and PWM stimulated proliferation were decreased. Decreased responsiveness to PWM was abrogated by preculturing PBMC in media alone before PWM stimulation. Decreased responsiveness to PHA was not reversed by a similar period of preculture.

To further define the above abnormalities in immunoregulation we examined mononuclear subpopulations. In controls, adding purified T cells or Con A activated lymphocytes to autologous cultures which had been stimulated with PHA and PWM significantly decreased proliferative activity. No such suppressive activity of T cells or Con A activated cells from the patient or family members was noted.

These data demonstrate an absent or functionally inactive spontaneous and Con A activated T suppressor cells in the family of a patient with Waldenström's macroglobulinemia.
Simultaneous occurrence of mycosis fungoides and hodgkin disease: Clinical and histologic correlations in three cases with ultrastructural studies in two
Authors: Hawkins Katherine A. , Schinella Roger , Schwartz Melvin , Ramsey David , Weintraub Arthur H. , Silber Robert , Amorosi Edward L.
Published: February 2007

We present three patients who manifested both Hodgkin disease and mycosis fungoides. Ages ranged from 39 to 66 and two were male. Skin lesions were present from 3 to 40 years before the diagnosis of Hodgkin disease. In all cases, mycosis fungoides was confirmed histologically by skin biopsy; the clinical course of the mycosis fungoides was indolent in all cases. Hodgkin disease was confirmed histologically in three, and confirmed by electron microscopy in two. All three patients responded to appropriate treatment for Hodgkin disease and are alive and well at the present time.
Antithrombin III progressive function: A biochemical analysis
Authors: Gomperts Edward D. , Izadi Parvin
Published: February 2007

Antithrombin III (AT III) was isolated by two procedures using polyethylene glycol 4000 (PEG) precipitation as the first stage. The PEG supernatant (PEG‐sup) was applied to a heparin‐affinity chromatographic system and AT III‐heparin cofactor (AT III‐HCF) was isolated. The PEG precipitate (PEG‐ppt) was separated by a Sephacryl S‐200 column. Fractions were collected and those demonstrating maximum AT III antigen and progressive thrombin inhibition were pooled and reapplied to the washed Sephacryl S‐200 column. Fractions were again collected and assayed via specific antisera for AT III, α1‐antitrypsin (α1AT), α2‐macroglobulin (α2M), and α1‐acid glycoprotein (α1AG). AT III antigen (AT III AGN) and progressive function were confined primarily to one peak containing virtually no α2‐M, a low level of α1AT, and moderate quantities of α1AG. The PEG‐sup, PEG‐ppt, AT III‐HCF, and the fraction obtained after two passes across Sephacryl S‐200 (S#2) were similar in that they showed reactivity with specific AT III antisera and demonstrated heparin cofactor activity. They differed, however, in that the PEG‐sup and AT III‐HCF demonstrated considerably reduced progressive antithrombin function assesed over 30 min. This function was present in the PEG‐ppt and S#2 fractions and this progressive activity was potentiated by EDTA. AT III two‐dimensional immunoelectrophoresis (2‐DIE) in the presence of heparin of both the Sephacryl and heparin‐affinity purified components were very different, with the Sephacryl‐purified AT III AGN showing both a fast peak and a very prominent slow‐moving hump. The AT III heparin affinity fraction showed primarily a fast component. Dilution of the S#2 and PEG‐ppt fractions resulted in considerable loss of the progressive activity and also the slow‐moving component on 2‐DIE. On the basis of these observations, it is postulated that AT III purified by PEG precipitation is in an aggregated from and that aggregate formation and dissolution is associated with AT III progressive activity.
Acute lymphoblastic leukemia: End‐result analysis of treatment and prognostic factors in Indian patients
Authors: Advani S. H. , Rao D. N. , Gopal R. , Nair C. N. , Battacharya M.
Published: February 2007

Acute Lymphatic Leukemia (ALL) patients seen during the period 1974–1978 at the Tata Memorial Hospital, Bombay, are analyzed retrospectively to evaluate the clinical features at presentation, results of sequential therapy, and prognostic factors. A total of 301 patients were registered during the study period. There were 153 evaluable patients. Of these 73 patients received induction therapy with vincristine and prednisolone (VP) followed by cranial prophylaxis (cranial radiotherapy, 2,400 rads, and 10 weekly intrathecal injections of methotrexate 7.5 mg/m2) and continuous oral maintenance with daily 6‐mecrapatopurine and weekly methrotrexte (group A). Another 39 patients (group B) received pulse therapy with vincristine and prednisolone during maintenance therapy. Finally 41 patients (group C) received L‐asparaginase during induction and pulse therapy in addition to drugs as in group A. Of the 153 patients, 88 (58%) achieved complete response after induction treatment.

Induction remission was 53% with vincristine and prednisolone (group A and group B), whereas it was 70% in group C. The difference in complete response rate in group C was statistically significant (P<0.05). The 3‐year survival in our series was 22%, with median survival of 11 months. Group C patients receiving L‐asparaginase along with vincristine and prednisolone showed 41% 3‐year survival compared to 16% for group B. The 3‐year survival in group A patients was only 7%, probably owing to lack of pulse therapy during maintenance treatment. The prognostic factors such as age, sex, WBC count, and mediastinal node were compared for induction remission and total survival. Possible factors relating to poor results in our series as compared to developed countries are discussed.
Diminished adherence of sickle erythrocytes to cultured vascular endothelium by piracetam
Authors: Nalbandian Robert M. , Henry Raymond L. , Burek C. Lynne , Diglio Clement A. , Goldman Arnold I. , Taylor Gregory W. , Hoffman William H.
Published: February 2007

Erythrocytes from both normal and sickle cell donors were incubated on a bed of cultured rat vascular endothelial cells. Although the adherence of the erythrocytes to the endothelial cells was equivalent for both classes of donor, addition of 1.5 mM piracetam significantly decreased this adherence regardless of donor.
A rapid in vitro drug‐sensitivity assay in acute nonlymphocytic leukemia
Authors: Theodorakis Michael E. , Goldberg Jack
Published: February 2007

Leukemic myeloid, myelomonocytic, and monocytic cells will incorporate radiolabeled sulfate into newly synthesized macromolecules. We developed a liquid culture technique to examine the in vitro effects of chemotherapeutic agents on the incorporation of radiolabeled sulfate into cells of patients with acute nonlymphocytic leukemia (ANLL). Cells recovered from bone marrow or peripheral blood of 25 patients with ANLL were incubated in vitro for one hour with saline (control) or a variety of chemotherapeutic agents. Cells were washed free of the drug and grown in liquid cultures containing nutrient medium and 35SO4. The percent of 35SO4 incorporated into the drug treated as compared with control cells was determined after one, three, and seven days of culture. Patients whose drug‐treated cells incorporated less than 30% of 35SO4 when compared with the control after three or seven days of culture achieved a complete response to these agents in vivo (P < .05). Thus, the in vitro effects of various chemotherapeutic agents on the incorporation of 35SO4 into cells obtained from patients with ANLL may help predict clinical response to these agents in vivo.
Opsonized‐zymosan induces a respiratory burst in human blood platelets
Authors: Principe D. Del , Menichelli A. , D'Arcangelo C. , Strappini P. M. , Persiani M. , Colistra C. , Scarpati M. L.
Published: February 2007

Opsonized‐zymosan‐stimulated polymorphonuclear cells show a cyanide‐insensitive oxygen consumption. We have investigated whether opsonized‐zymosan could induce similar metabolic change in human blood platelets. Preparation of intact human blood platelets, obtained by separation through a Ficoll layer (23% w/v) were challenged with opsonized‐zymosan. the polymorphonuclear cell contamination was less than 1/108 platelets. The opsonized‐zymosan‐stimulated platelets showed an increase of oxygen consumption. The mean of xygen burst measured by a polarographic method with a Clark electrode was 11 nmole/109 platelets/min (S.E.M. 4; n = 15). The duration of the burst was 2 min. Unstimulated platelets did not show the oxygen burst. The inhibitors of respiratory chain and prostaglandin synthesis completely abolished the oxygen consumption by opsonized‐zymosan‐stimulated platelets. The simultaneous addition of NADH (1 mM) and opsonized‐zymosan induced a burst of oxygen consumption, which occurred after a variable lag phase (10‐2 min) from the stimulation, also in the presence of inhibitors. This burst, which lasted about 1 min. amounted to 10 nmole/109 platelets/min (S.E.M. 2; n = 15) and it was higher in the presence of NAN3 a catalase inhibitor. Zymosan treated with hydrazine or heated plasma (56°C) did not cause increased oxygen consumption. Inulin or inulin‐treated serum did not stimulate platelets. In these experimental conditions some NADH disappeared, as shown by isotachophoresis. The results demonstrated that an immunological stimulus may activate a membrane‐linked cyanide‐insensitive oxygen metabolizing system.
Aplastic anemia associated with intravenous chloramphenicol
Authors: Alavi Jane B.
Published: February 2007

A patient is presented who developed aplastic anemia 3 months after exposure to intravenous chloramphenicol. She died of this disease 4 years later. Other cases of marrow aplasia due to parenteral chloramphenicol are reviewed, in order to emphasize that this complication, although rare, is not restricted to the use of oral chloramphenicol.
Blastic transformation of chronic lymphocytic leukemia
Authors: Januszewicz Elchanan , Cooper Ian A. , Pilkington Glenn , Jose David
Published: February 2007

A case is described of a patient with chronic lymphocytic leukemia whose disease underwent blastic transformation. The transformed cells had the same immunoglobulin types (μ and k) as the original chronic lymphocytic leukemia cells. Immunoperoxidase staining technique demonstrated that, in the transformed cells of the bone marrow, much of the immunoglobulin was intracellular. In the peripheral blood the transformed cells had dense surface immunoglobulin and features of primitive T‐cells. These findings suggest that transformation to an immunoblastic type of leukemia had occurred.
Effect of a perfluorocarbon emulsion (Fluosol‐DA) on reticuloendothelial system clearance function
Authors: Castro Oswaldo , Nesbitt Aleta E. , Lyles Denise
Published: February 2007

To study the effect of a perfluorocarbon oxygen transport emulsion (Fluosol‐DA) on reticuloendothelial system (RES) function, we measured the blood clearance of human erythrocytes transfused to rats. Compared with saline treatment, Fluosol‐DA at 30 ml/kg doses significantly increased both the percent 20‐hour blood recovery (mean 8.9% ± 2.7 SEM vs 1.3% ± 0.25 SEM) and 51Cr t1/2 survival (mean 14.0 hours ± 2.7 SEM vs 3.5 hours ± 0.33 SEM) of the human red cells. This suppression of RES clearance function was transient and no longer detectable seven days after single Fluosol‐DA doses. The Fluosol‐DA‐induced RES block was about three times greater than that obtainable with 4 g/kg of a soybean oil emulsion used for clinical hyperalimentation. On the other hand, the effect of ethyl palmitate (0.5 g/kg), a potent but toxic RES blocker, was 3.5 times greater than that of Fluosol‐DA in this test system. If Fluosol‐DA also induces RES block in humans, this emulsion could be explored as a therapeutic RES blocker in certain immune cytopenias.
β Globin messenger RNA content of bone marrow erythroblasts in heterozygous β‐thalassemia
Authors: Benz Edward J. , Pritchard Jonathan , Hillman Diane , Glass Jonathan , Forget Bernard G.
Published: February 2007

RNA from bone marrow erythroblasts and peripheral blood reticulocytes of patients with heterozygous β‐thalassemia was analyzed for relative content of α and β globin messenger RNA by molecular hybrization. Erythroblasts from nonthalassemic patients exhibited approximately the same α and β globin mRNA content (β/α mRNA ratio = 0.8–1.0) as circulating reticulocytes (β/α mRNA ratio = 0.74–1.2). The mRNA ratios corresponded well to levels of globin synthesis observed in bone marrow and peripheral blood. Erythroblasts from four patients with heterozygous β‐thalassemia also exhibited approximately the same β/α mRNA ratios in bone marrow erythroblasts (0.34–0.59) as in reticulocytes (0.34–0.4): β globin mRNA was clearly deficient in bone marrow erythroblasts. Globin biosynthesis by erythroblasts of β‐thalassemia heterozygotes was balanced despite the mRNA deficiency (β/α = 0.9–1.0), suggesting that post‐translational phenoma (eg, proteolysis of free globin chains), rather than instability of β mRNA, accounts for the balanced globin chain synthesis frequently observed in bone marrow erythroblasts of patients with β‐thalassemia trait.
Hemoglobin Hamilton or α2β211(a8)Val→Ile: A silent β‐chain variant detected by triton X‐100 acid‐urea polyacrylamide gel electrophoresis
Authors: Wong S. C. , Ali M. A. M. , Lam H. , Webber B. B. , Wilson J. B. , Huisman T. H. J.
Published: February 2007

A silent β‐chain hemoglobin variant, not detectable by starch gel or agar gel electrophoresis was found using Triton X‐100 acid‐urea polyacrylamide gel electrophoresis. The abnormal β‐X chain had a more anodic electrophoretic mobility; 38% of the total β chain was of the abnormal type. Structural analysis using high‐performance liquid chromatography and microsequencing procedures indicated a valine to isoleucine substitution at position β11(A8). This anomaly did not change the functional proper ties of the hemoglobin molecule. A mild reticulocytosis was observed in the propositus.
Initial alkylating agent chemotherapy in a leukemic hairy cell patient
Authors: Gaynor Ellen , Golomb Harvey M. , McClellan Jason
Published: February 2007

A patient with moderate splenomegaly and the leukemic phase of hairy cell leukemia presented with a white blood cell count (WBC) of 85,600/mm3 with 87% hairy cells and platelets of 125,000/mm3. Initial therapy consisted of chlorambucil alone at 4 mg each day. Within 6 months, the WBC decreased to 27,000/mm3 with 82% hairy cells, and the spleen was not palpable; platelets remained at 142,000/mm3. The patient has continued to do well for 2 years since the start of therapy, requiring no transfusions and having no problems secondary to organ infiltration. Selected hairy cell patients, those with a significant leukemic phase and with only mild thrombocytopenia, may benefit from initial chlorambucil therapy rather than immediate splenectomy.
Quinidine‐induced agranulocytosis
Authors: Alexander Saramma J. , Gilmore Robin I.
Published: February 2007

A case of agranulocytosis in an 86‐year‐old man after 8 weeks treatment with quinidine sulfate is described. Acute phase serum from the patient demonstrated antineutrophil activity by the microgranulocytotoxicity assay. Review of the literature reveals that more than one mechanism could cause this idiosyncratic immune‐mediated agranulocytosis.
Hemoglobin S levels in sickle cell trait individuals
Authors: Cameron Bruce F. , Smith Diane B. , Cody Barbara
Published: February 2007

Changes in Department of Defense regulations now permit persons with sickle cell trait to serve in all service branches. However, for purposes of the regulation, sickle cell trait is defined as 41% or less S hemoglobin. Our screening experience, based on 397 individuals with sickle cell trait, with quantitative scan of cellulose acetate electrophoretic sheets, indicates that 20–40% (depending on definition of terms) of individuals with sickle cell trait would be excluded by this criterion.
Decreased sodium influx and abnormal red cell membrane lipids in a patient with familial plasma lecithin:Cholesterol acyltransferase deficiency
Authors: Murayama Naoki , Asano Yasushi , Hosoda Saichi , Maesawa Masaji , Saito Masaki , Takaku Fumimaro , Sugihara Takashi , Miyashima Kosuke , Yawata Yoshihito
Published: February 2007

Red cell membrane metabolism in familial lecithin:cholesterol acyltransferase (LCAT) deficiency was investigated. The family presented here is the third case discovered in Japan. An increase of free cholesterol was observed in the red cell membranes, concomitant with increased phosphatidyl choline. Osmotic fragility of the patient's red cells was diminished rather than increased. Red cell survival (51Cr T1/2) was shortened (15 days). Sodium influx was markedly decreased, although sodium efflux, both ouabain‐sensitive and ouabain‐insensitive, was normal. The activity of acetyl‐cholinesterase as a marker of the outer leaflet of the red cell membranes was decreased, while the activity of glyceraldehyde‐3‐phosphate dehydrogenase as a marker of the inner leaflet was normal. No abnormalities of adenosine triphosphatases in red cell membranes were observed. These results suggest that the alteration of cholesterol metabolism in the plasma of LCAT deficiency increases the red cell membrane cholesterol and affects the functions of the red cell membranes, especially of the outer leaflet, which may result in decreased sodium influx.
Tumor lysis syndrome following VP‐16‐213 in chronic myeloid leukemia in blast crisis
Authors: Thomas M. Roy , Robinson W. A. , Mughal T. I. , Glode L. Michael
Published: February 2007

Several recent reports have emphasized the potentially serious and often fatal acute metabolic complications following cytotoxic chemotherapy in both solid tumors and leukemias. We present here a case of chronic myeloid leukemia in blast crisis who developed an acute tumor lysis syndrome following a single dose of VP‐16‐213 (Etoposide).
Impaired metabolic activity of phagocytosing neutrophils in agnogenic osteomyelofibrosis with splenomegaly: A longitudinal study
Authors: Marquetty Claude , Labro‐Bryskier Marie‐Thérèse , Perianin Axel , Hakim Jacques
Published: February 2007

Functional and enzyme activity of neutrophils in patients with agnogenic osteomyelofibrosis (AOM) is still a subject of controversy, probably owing to the heterogeneity of the abnormalities observed from patient to patient, and the absence of longitudinal studies performed during the course of the disease. For a better definition of these abnormalities, 40 patients with untreated AOM were studied from the time of diagnosis, and in 12 cases, neutrophil function and enzyme activity were reassessed at one‐year intervals for 3–5 years. The results showed that all abnormalities were serum‐independent. Mean ingestion rate in neutrophils from patients were similar to that of the controls but individual values were more varied, with some very high and some low ingestion rates. Histochemical latex ingestion and nitroblue tetrazolium reduction were lower in patients than in controls, as were cyanide‐insensitive O2 consumption and superoxide anion and H2O2 production. Mean iodination was also decreased and, in most patients, was related to a decrease in H2O2 production. However, in eight patients H2O2 production was normal, although an iodination deficiency was found. Myeloperoxidase activity was low in five of these cases. In the other three patients this discrepancy was not explained. The longitudinal study of 12 patients showed that defects observed in the early stages of the disease remained or were aggravated, and that new abnormalities appeared during the course of the disease.
Lymphocyte subsets in patients with aplastic anemia
Authors: Ruiz‐Argüelles G. J. , Katzmann J. A. , Greipp P. R. , Marín‐López A. , González‐Llaven J. , Cano‐Castellanos R.
Published: February 2007

Lymphocyte subsets were enumerated in a group of 31 patients with aplastic anemia. Abnormal numbers of immunoregulatory T‐cells were found in some patients: 26% of them showed a reversed helper/suppressor ratio. Seven of 18 patients showed significantly decreased proliferation in response to PWM; this hyporesponsiveness was present in 75% of patients with a reversed helper/suppressor ratio and in 10% of those with a normal helper/suppressor ratio (R = 0.66, P = 0.008). Eight of 18 patients showed suppressor activity over PWM‐induced allogeneic cell proliferation. This suppressive activity did not correlate with T‐cell phenotype. Of the patients with a low number of T‐cells, 73% had responded to treatment, whereas of those patients with a normal number of T‐cells, 26% had responded (P = 0.016). The results are consistent with abnormal immune response in selected patients with aplastic anemia, and suggest a possible influence of T‐cells on disease process.
The total marrow mass of the mouse: A simplified method of measurement
Authors: Boggs D. R.
Published: February 2007

The total number of nucleated cells in the long bone of a mouse can be determined with some accuracy. Thus, in this species, values for marrow cells can be expressed as a total cell count per bone, a more meaningful number than values expressed as concentration as is done in most studies of other species. If the percent of total marrow in the skeleton that is contained in that bone is known, values can be expressed as “per mouse” (total marrow mass)–‐a still more meaningful value than values per bone. The total marrow mass of mice has been calculated previously on the basis of nucleated cells per humerus or per femur and the percent of the total marrow contained in that bone. However, that percent was based on rather tedious dissection of the entire skeleton and determining the amount of 59Fe that had been taken up by each bone. In the present study, mice were injected with 59Fe, skinned, and eviscerated. The carcass was then either cooked and all bones dissected out or simply cut into pieces containing various bones or bone groups. The percent of 59Fe taken up by various bones or bone groups as measured by the two techniques was virtually identical. The percent distribution between various bones was found to be fairly constant between 4 and 18 h after 59Fe injection and the same in mice aged 3 or 12 months. This simplified technique makes the measurement of total marrow mass a practical addition in studies of murine hematopoiesis.
The effect of lithium carbonate on chemotherapy‐induced neutropenia and thrombocytopenia
Authors: Richman Carol M. , Makii Michael M. , Weiser Patricia A. , Herbst Arthur L.
Published: February 2007

Lithium carbonate ameliorates neutropenia associated with cancer chemotherapy. The effect of lithium on platelet suppression has not, however, been well established. In the present study, five patients with ovarian carcinoma received daily lithium during alternate cycles of treatment with hexamethylmelamine, cyclophosphamide, adriamycin, and cis‐platinum. Analysis of myelosuppression was performed on 24 paired consecutive cycles given at identical doses, one with and one without lithium. During lithium cycles, nadir leukocyte, neutrophil, and platelet counts were significantly higher (P<0.01, <0.01, <0.05 respectively) and the interval between treatments was shorter (P<0.01). One patient who has received 11 cycles of chemotherapy continues to receive 100% doses owing to the beneficial effect of lithium on chemotherapy‐induced thrombocytopenia. Lithium was poorly tolerated by some patients because of either tremor or nausea and vomiting, in spite of nontoxic serum lithium levels. The amelioration of drug‐induced platelet suppression as well as neutrophil suppression noted in this study suggests that lithium's effect on hematopoiesis is not limited to stimulation of neutrophil production. The ability of lithium to decrease chemotherapyinduced myelosuppression suggests that lithium administration may facilitate escalation of chemotherapy doses in selected patients.
The effects of PGF2α, PGI2, and TXB2 on human CFU‐C in healthy and leukemic patients
Authors: Gross Samuel , Worthington‐White Diana A.
Published: February 2007

This study was undertaken to test the effects of certain arachidonate derivatives, PGF2α, PGI2 and TxB2 on in vitro bone marrow granulocyte colony growth (CFU‐C) in leukemia patients receiving maintenance chemotherapy and in normal controls. The addition of PGF2α did not result in increased numbers of colonies, but it did cause a shift in the size of the colonies so that there was a significant increase in larger colonies (P < 0.001) and significantly fewer small colonies (P < 0.05) as compared to untreated samples. Of the prostenoids tested in a Tris‐buffered system, PGI2 affected the greatest increase in CFU‐C (P < 0.01) followed by PGF2α (P < 0.05) whereas 6‐keto‐PGF1α (the stable hydrate of PGI2) did not affect colony growth. Time‐response curves revealed a linear growth pattern for PGF2α with a peak at 10 days, whereas there was a 6‐day growth lag with PGI2 followed by linear growth with a peak at 13 days. TxB2 added to cultures significantly reduced the number of bone marrow CFU‐C at all doses tested.

The prostanoid effects on CFU‐C derived from leukemic patients on maintenance chemotherapy and from normal individuals were identical in every respect.
Increased prevalence of polycythemia vera in parents of patients on polycythemia vera study group protocols
Authors: Brubaker Leonard H. , Wasserman Louis R. , Goldberg Judith D. , Pisciotta Anthony V. , McIntyre O. Ross , Kaplan Manuel E. , Modan Baruch , Flannery John , Harp Rollie
Published: February 2007

An investigation of relatives of 652 patients entered on studies of the Polycythemia Vera Study Group yielded five documented cases of the disease among the parents of patients. When compared with expected values based on the Connecticut Tumor Registry and other population studies a significant increase was found in the lifetime incidence of polycythemia vera in parents of these patients.
The relationship between fetal hemoglobin level and glycosylation in sickle cell disease
Authors: Elseweidy M. M. , Abraham E. C.
Published: February 2007

Glycosylated hemoglobin (glyco Hb) was determined by affinity chromatography and Hb S1 and Hb F by Bio‐Rex 70 chromatography in patients with sickle cell anemia, SC disease, Sβ+‐thalassemia, and Sββ‐thalassemia. SC and Sβ‐thalassemia patients had normal levels of glyco Hb whereas SS patients had significantly lower levels. Within each group of patients a direct correlation existed between Hb F and glyco Hb or Hb S1 levels. A similar relationship was noticed when glyco Hb and Hb F levels were compared in red cell populations of various densities (ages). Hb F seems to influence glycosylation through its effect on red cell survival.
Peripheral blood lymphocytes with receptors for a determinant common to B‐lymphoblastoid cell lines and acute myelogenous leukemia blasts
Authors: Lichtenstein Alan , Naiem Faramarz , Zighelboim Jacob
Published: February 2007

We investigated whether the rosetting of B‐lymphoblastoid cell lines (B‐LCL) by peripheral blood lymphocytes (PBLs) reflected possible interactions between lymphoid cells and immature cells of the hematopoietic system. Rosette formation could be blocked by the addition of soluble antigen extracted from B‐LCL or blasts obtained from patients with acute myelogenous leukemia (AML). This inhibition was specific for AML blasts (similarly extracted material from melanoma lines had no inhibitory effect) and for the B‐LCL receptor (leukemic extracts had no effect on surface receptors for sheep red blood cells (E) or antibody‐sensitized red blood cells (EA)). The B‐LCL receptor is present on leukemic Sezary T‐cells as well as normal T‐cells and its sensitivity to various enzymatic treatments is markedly different from that of E and EA receptors. In addition, B‐LCLs derived from in vitro EB‐viral infection of a normal donor's B lymphocytes were significantly rosetted by that donor's autologous PBLs. These data suggest the B‐LCL receptor, present on mature T‐cells, can recognize self determinants on myeloblasts and B‐LCL. Further investigation will determine whether this interaction can affect the function of rosetted target cells.
Pancytopenia with hypercellular bone marrow—a possible paraneoplastic syndrome in carcinoma of the lung: A report of three cases
Authors: Raz Itamar , Shinar Eilat , Polliack Aaron
Published: February 2007

Three patients with idiopathic pancytopenia and hypercellular bone marrow who developed carcinoma of the lung within two years of diagnosis are reported. All three patients had macrocytic anemia associated with a megaloblastic marrow in the presence of normal serum vitamin B12 and folic acid levels. Neutropenia with monocytosis, elevated serum muramidase and LAP scores, and increased fetal hemoglobin levels were also found. In all cases Ham's tests were negative with a normal bone marrow karyotype. In all three patients, pancytopenia due to myelodysplasia, a probable preleukemic state, was diagnosed initially prior to the appearance of carcinoma of the lung.

One of the patients showed improved leukocyte and platelet counts during chemotherapy, while the other two died before chemotherapy could be administered. In the light of the above findings we suggest that carcinoma of the lung may be the cause of a paraneoplastic syndrome with pancytopenia, particularly in patients with a hypercellular marrow with a normal karyotype.
Functional diversity within the suppressor phenotype as defined by monoclonal antibody in T‐cell prolymphocytic leukemia
Authors: Zamkoff Kenneth W. , Poiesz Bernard J. , Ruscetti Francis W. , Moore Janet L. , Davey Frederick R. , Planas Antonio T. , Lamberson Harold
Published: February 2007

A patient with T‐cell prolymphocytic leukemia (T‐PLL) is described. The malignant T‐cells from the patient were predominantly Leu‐2‐positive, indicating a suppressor phenotype. The cells were then tested to determine their functional capabilities. The patient's Leu‐2‐positive cells initially suppressed B‐cell proliferation, as predicted by their phenotype but later functioned as T helper cells in the pokeweed mitogen system without a change in phenotype. The cells also responded inadequately to alloantigen and mitogen despite addition of exogenous T‐cell growth factor (TCGF). Leu‐2‐positive prolymphocytes from the spleen of the patient were constitutive producers of TCGF. Surface phenotype using monoclonal antibody was inadequate to predict T‐cell function of the cells from this patient with T‐PLL. In addition, these data suggest there may be functional subpopulations within the OKT8 + phenotype. Constitutive TCGF production by malignant post‐thymic T‐cells may represent a mechanism by which these cells sustain their own growth.
Increase in density and accumulation of serotonin by human aging platelets
Authors: Mezzano Diego , Aranda Eduardo , Rodríguez Soledad , Foradori Arnaldo , Lira Pablo
Published: February 2007

51Cr‐labeled autologous platelets were infused into splenectomized subjects and the specific radioactivities of high‐density (HD) and low‐density (LD) platelet subpopulations were determined sequentially in postinfusion samples. A rapid decrease in the specific radioactivity of LD cohorts (T 1/2 = 2.5 days) was observed, but the specific radioactivity of HD platelets remained constant or increased slightly during the first 4 days and then gradually declined for the next 5 days. No experimental artifacts during the platelet‐labeling steps that could account for these results were demonstrated. These findings confirm previous observations in eusplenic individuals and support the hypothesis that human LD platelets are, on the average, younger than HD platelets.

LD platelets contain 33.8 ± 13.5 ng serotonin (5HT)/108 platelets and HD platelets 76.8 ± 9.5 ng 5HT/108 platelets (P < 0.001). Sequential measurements of 5HT in PRP platelets were performed during the recovery phase of thrombocytopenia following splenectomy in patients with idiopathic thrombocytopenic purpura (ITP), a condition associated with aging of platelets in circulation. Presplenectomy platelet 5HT was 17.7 ng/108 platelets and on days 1, 6, and 12 after surgery it increased to 18.1, 37.8, and 61.0 ng/108 platelets (n = 7). When three healthy volunteers were given aspirin (500 mg/day) for up to 15 days, no significant change in the 5HT content of circulating platelets was observed. If aspirin blocks, at least partially, the secretory process in vivo without interfering the 5HT uptake by the platelets, this finding stands against the possibility that a net depletion of 5HT occurs during the life‐span of normal human platelets.

The observation that human HD platelets, enriched with older cells, contain more 5HT than LD platelets taken together with the parallel increase in platelet 5HT and age during the recovery from thrombocytopenia in ITP patients and the lack of effect of aspirin on platelet 5HT content, provides initial evidence that human platelets accumulate 5HT during their life‐span in circulation.