bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased sialic acid content of erythrocytes in patients with aplastic anaemia
Authors: Yoshida Minore , Takaku Fumimaro , Nojiri Hlsao , Miura Yasusada , Saito Masaki 
Published: March 2008

Summary.The sialic acid content of erythrocytes from patients with aplastic anaemia was determined and compared with those in patients with several haematological disorders and healthy individuals. The sialic acid was released enzymatically with Vibrio cholerae sialidase and quantitated by the thiobarbituric acid method (Aminoff, 1961). The sialic acid content of normal erythrocytes was 538 ±31 nmol/ml of packed erythrocytes. That of erythrocytes from patients with aplastic anaemia was 480±35 nmol/ml of packed erythrocytes, which was significantly lower than normal (P<0.01).In contrast, erythrocytes from patients with myeloproliferative disorders showed significantly (P<0.05) higher sialic acid contents (564±45 nmol/ml of packed erythrocytes). These results suggest that some membrane changes occur in erythrocytes in patients with these disorders.
Fluorouracil (5‐FU) induced acute immune haemolytic anaemia
Authors: Sandvei P. , Nordhagen R. , Michaelsen T. E. , Wolthuis K. 
Published: March 2008

Summary.A female patient on Fluorouracil (5‐FU) therapy for rectal carcinoma developed acute intravascular haemolysis with her fifteenth drug injection; a similar episode occurred later after a controlled challenge with the drug. A 5‐FU‐dependent complement‐activating IgM antibody, which reacted with RBC in an indirect antiglobulin test, was detected in her serum. The antibody did not react with cord RBC, but a blood group specificity could not be determined. An excess of 5‐FU in the indirect antiglobulin tests resulted in inhibition of these reactions.
Long survival in B‐CLL correlates with surface IgMK phenotype
Authors: Hamblin T. J. , Oscier D. G. , Stevens J. R. , Smith J. L. 
Published: March 2008

Summary200 patients with B‐cell chronic lymphocytic leukaemia (B‐CLL) presenting to a single centre over 13 years have been studied. In 72.2% the diagnosis was made on an incidental blood count, and 70.1% were stage A at presentation. Those patients whose cells expressed surface IgMK were significantly more likely to be stage A at presentation and significantly less likely to have a lymphocyte count >50x 109/1, to have progressive disease or to require treatment than those with other classes of surface Ig. Patients whose cells express surface IgMK have a significantly longer actuarial survival than others and this is also so when only patients in Binet stage A or when only patients presenting below the age of 75 are studied. By studying all of the cases presenting in a single catchment area we have attempted to avoid the bias against trivial disease likely to be seen in specialist referral centres.
Relationship of serum lactate dehydrogenase level with first remission length in adult acute lymphocytic leukaemia
Authors: Fasola Gianpiero , Fanin Renato , Baccarani Michele , Zuffa Eliana , Haanen Clemens , Comotti Benedetto , Scapoli Gianluigi , Alghisi Alberta , Battista Raffaele , Aieta Michele , Fiacchini Mauro , Tura Sante 
Published: March 2008

SummarySeveral features have a prognostic value in adults with acute lymphocytic leukaemia (ALL). However, in about two‐thirds of all cases prognosis remains quite variable, with a substantial number of early relapses. This study shows in 118 adult patients who attained complete remission (CR) between 1978 and 1984 that pretreatment serum total lactate dehydrogenase (LDH) activity was inversely correlated with first CR length. The prognostic value of LDH was higher than that of any other features both in univariable and in multivariable analysis. The value was significant in the whole series as well as in patients who lacked other high risk features. Among non‐high risk and low‐WBC count cases, patients with LDH > 500 U/l had a median first CR duration of 27 months, and a projected 5‐year relapse free survival of 36%, versus 9 months and 12% of patients with LDH > 500 U/l. These results fit well with the results of a study of ALL in children, and suggest that pretreatment serum total LDH activity is an important risk determinant in adult ALL.
Erythrocyte pyruvate kinase deficiency: 11 new cases
Authors: Zanella A. , Colombo M. B. , Miniero R. , Perroni L. , Meloni T. , Sirchia G. 
Published: March 2008

Eleven new cases of red cell pyruvate kinase (PK) deficiency with congenital haemolytic disease from 10 unrelated Italian families were characterized using the methods recommended by the International Committee for Standardization in Haematology (ICSH). All patients were double heterozygotes for the PK gene. The 10 variants were designated PK ‘Lecce,’‘Parma,’‘Verona,’‘Milano,’‘Soresina,’‘Macerata,’‘Sassari,’‘Genova,’‘Mantova’and ‘Brescia.’PK ‘Sassari’was associated with glucose‐6‐phosphate dehydrogenase deficiency in two siblings. All mutants displayed multiple biochemical abnormalities except for PK ‘Lecce’that only showed decreased red cell PK activity. No relation was found between the severity of anaemia and either the residual PK activity or specific biochemical enzyme abnormalities.Increased serum ferritin levels were detected in most of the patients, suggesting the need for systematically monitoring iron status in this disease.
Transplantation of embryonic haemopoietic stem cells without prior recipient X‐irradiation
Authors: HOLLANDS P. 
Published: March 2008

Allogeneic day 7 mouse embryonic cells can colonize the haemopoietic system of normal, non‐irradiated recipient mice. Donor embryonic cells are disaggregated and injected intravenously resulting in colonization in 40% of recipients, as shown by the presence of electrophoretic markers, characteristic of the donor cells. Donor type haemoglobin (Hb) and donor type glucose phosphate isomerase (GPI) demonstrates the presence of donor type erythrocytes and lymphocytes respectively. Repeat grafts in recipients not showing donor markers did not result in colonization. Recipient type haemopoiesis was dominant in all types of recipient. Skin grafts of allogeneic donor type skin onto successfully grafted embryonic cell recipients did not survive. Allogeneic donor embryonic cells therefore survive in recipients where adult skin allografts do not.Donor embryonic cells, homozygous for T6 marker chromosomes, were used to assess the site of colonization of intravenously grafted cells. Donor chromosomes were seen in recipient liver and bone marrow at low levels. This distribution of donor cells persists for up to 64 d post‐graft.
Acquired alpha‐2‐antiplasmin deficiency in acute promyelocytic leukaemia
Authors: Avvisati Giuseppe , Ten Cate Jan W. , Sturk Augueste , Lamping Roy , Petti Maria C. , Mandelli Franco 
Published: March 2008

We report a prospective study in nine consecutive adult patients with acute promyelocytic leukaemia (APL). The study objective was to assess the prevalance of activation of blood coagulation and/or activation of fibrinolysis in APL. Coagulation and fibrinolytic parameters relevant to the objective included antithrombin III, plasminogen, fibrin/fibrinogen degradation products and alpha‐2 antiplasmin activity and antigen levels. The results of this study revealed consistently normal antithrombin III levels, both before and in the course of antileukaemic treatment. Plasminogen levels were slightly decreased or normal. However, a distinct alpha‐2 antiplasmin activity deficiency in all patients was observed with levels even reaching zero in three patients, during chemotherapy. Alpha‐2 antiplasmin activity levels were consistently lower than the alpha‐2 antiplasmin antigen levels. The in vitro binding of alpha‐2 antiplasmin activity to fibrin clots was severely reduced which appeared to be due to the reduced alpha‐2 antiplasmin plasma levels. Upon crossed‐immunoelectrophoresis against alpha‐2 antiplasmin antiserum two alpha‐2 antiplasmin antigen peaks were observed in the plasma of all nine patients. All abnormalities were reversible 4 d after completion of chemotherapy.In a second series of 12 consecutive APL patients we confirmed the consistency of the alpha‐2 antiplasmin activity deficiency and normal antithrombin III plasma levels. In addition Protein C activity and antigen levels were normal or near normal in 10 and reduced in two patients. Thrombinantithrombin III complexes were increased in 10 and normal in two patients.We conclude that some activation of blood coagulation is present in APL (increased thrombin‐antithrombin III complex levels) but its contribution to the coagulopathy seems to be minor (normal antithrombin III and only slightly reduced protein C levels). The observed reduced alpha‐2 antiplasmin content of the fibrin clot in vitro may result in vivo in a fibrin clot that is highly susceptible to fibrin degradation, thus aggravating the coagulopathy in APL.
Hb S(C)‐β+‐thalassaemia: different mutations are associated with different levels of normal Hb A
Authors: Gonzalez‐Redondo J. M. , Kutlar F. , Kutlar A. , Stoming T. A. , De Pablos J. MA. , Kilinç Y. , Huisman T. H. J. 
Published: March 2008

Analysis of amplified DNA through hybridization with 32P‐labelled synthetic oligonucleotide probes has provided data about the molecular abnormality for β‐thalassaemic globin genes present in 32 Black and eight Mediterranean patients with Hb S(C)‐β+‐thalassaemia. The patients were categorized according to these β‐thalassaemia mutations, and average haematological and haemoglobin composition data were compared for each of four different groups. Twenty‐eight Black patients had the ‐29 AG substitution and four had the ‐88 CT substitution; all had mild disease with comparable haematology and an average Hb A level of 20%. Six Mediterranean patients had the IVS‐1, 110 GA mutation; their haematological data were nearly the same as that for the Black patients except for a lower Hb A value of 11%. Two Turkish patients with the IVS‐2, 745 CG mutation were more severely affected with mild sickling disease and low Hb A levels of 5%. Hb F levels varied greatly because of age differences; high Gγ values were observed only in patients with a β‐thalassaemia chromosome having an Xmn I site 5’to Gγ.The data readily explain the variability in Hb A level that has been repeatedly noted in patients with Hb S(C)‐β+‐thalassaemia.
Embryonic haemopoietic stem cell grafts in the treatment of murine genetic anaemia
Authors: Hollands P. 
Published: March 2008

Embryonic haemopoietic stem cells obtained from early post‐implantation mouse embryos can be successfully used in the treatment of murine genetic anaemia. Anaemic recipients had either chronic macrocytic anaemia, which was lethal without treatment, or mild anaemia without increased mortality. All successfully grafted recipients developed donor haemoglobin and glucose phosphate isomerase electrophoretic markers, indicating the presence of donor erythrocytes and lymphocytes. The minimum number of embryonic cells resulting in a successful graft in chronic macrocytic anaemia recipients was 0.8 × 106 nucleated cells. Athymic (nude) mice were also colonized by embryonic haemopoietic stem cells. Donor electrophoretic markers were seen but all recipients soon died, possibly of pneumonia.Bone marrow grafts into recipients with chronic macrocytic anaemia were not successful. Bone marrow grafts into recipients with mild anaemia resulted in some recipients showing donor markers. These recipients later died, showing symptoms of graft‐versus‐host disease.
Red cell aggregation during normal pregnancy
Authors: Huisman A. , Aarnoudse J. G. , Krans M. , Huisjes H. J. , Fidler V. , Zijlstra W. G. 
Published: March 2008

Summary Red cell aggregation (RCA) is responsible for the increase in whole blood viscosity at lower shear rates. RCA depends on the concentrations of red cells and plasma proteins with a high molecular weight and a large and asymmetrical spatial structure such as fibrinogen, immunoglobulin M and α2‐macroglobulin. During normal pregnancy, changes occur in all these concentrations. In a prospective study these changes and their influence on the resulting RCA were investigated in 24 healthy women with normal pregnancies. RCA was determined by light reflection measurement (syllectometry).RCA considerably increased during normal pregnancy in spite of the physiological haemodilution. The aggregation half time, used as a measure for RCA, decreased from an average non‐pregnant value of 5.6 s to 3.3 s at 37 weeks. Multiple regression analysis showed that the increase in RCA could be mainly attributed to the raised fibrinogen concentration. However, at 37 weeks other factors, in addition to fibrinogen, contribute significantly to the increase in RCA.
Biochemical studies on McLeod phenotype red cells and isolation of Kx antigen
Authors: Redman C. M. , Marsh W. L. , Scarborough A. , Johnson C. L. , Rabin B. I. , Overbeeke M. 
Published: March 2008

Summary Red cells of the McLeod blood group phenotype have weak Kell antigens, lack Kx antigen and have acanthocytic morphology. We have immunoprecipitated Kell antigens from McLeod red cells and show that they are markers on the same 93 kDa membrane protein that carries Kell antigens on normal red cells. However, as determined by Western immunoblotting, McLeod red cells have a marked deficiency of this protein. We have also studied the near‐neighbour relationship of McLeod and common Kell red‐cell membrane proteins by cross‐linking intrinsic sulphydryl groups by oxidation, catalysed with orthophenanthroline and copper, or by cross‐linking amino groups with dimethyl 3,3‐dithiobispropionimidate. Results were analysed by diagonal mapping in two‐dimensional gels. No abnormalities of membrane protein inter‐relationship were detected in McLeod red cells.We have isolated Kx antigen from K0 red cells by immuno‐precipitation with human alloimmune anti‐Kx serum, isolation of immune complexes from detergent‐solubilized cell membranes with protein A‐Sepharose and analysis of the eluted immune complex by SDS‐PAGE under reducing conditions. Kx antigen is a marker on a red‐cell membrane protein of approximately 37 kDa. K0 (Knull) red cells have about twice the amount of Kx antigen as do red cells of common Kell type. McLeod red cells have no detectable Kx antigen by serological tests or by immunoprecipitation.
A phorbol ester tolerant (PET) variant of HL‐60 promyelocytes
Authors: Macfarlane Donald E. , Gailani David , Vann Kenneth 
Published: March 2008

Summary The promyelocytic leukaemia cell line HL‐60 differentiates to a macrophage‐like cell when exposed to the phorbol ester 12–0‐tetradecanoylphorbol 13‐acetate (TPA) and other agents which activate protein kinase C. To investigate this phenomenon we developed an HL‐60 variant which does not differentiate when exposed to TPA. HL‐60 cells were exposed to the mutagen ethyl methanesulphonate and were cloned in soft agar in the presence of a normally lethal concentration of TPA. One colony of cells that proliferated in TPA was obtained. The cells of this phorbol ester tolerant (PET) line have retained their resistance to TPA for several years without selective pressure. They are some‐what larger than their phorbol ester sensitive (S) parent, but they are otherwise morphologically similar.When PET‐cells are exposed to TPA their growth is arrested for approximately 48 h. Thereafter, they resume their original rate of replication at all concentrations of TPA tested. S‐cells undergo changes typical of HL‐60 when exposed to TPA; they aggregate, stop growing, adhere to the flask and die. The PET‐cells appeared to be as sensitive as S‐cells to other agents which differentiate HL‐60 such as retinoic acid, dimethysulphoxide, and 1,25‐dihydroxyvitamin D3, as determined by rate of proliferation in culture, Wright's stain, nitroblue tetrazolium reduction, and induction of the ectoenzyme NAD‐glycohydrolase.TPA‐induced protein phosphorylation was studied using one‐and two‐dimensional polyacrylamide gel electrophoresis. Several proteins increased their incorporation of 32P when S‐ and PET‐cells were exposed to TPA, the most prominent of which were the two previously described nuclear matrix proteins of 80 kd and 33 kd. There was no difference in the protein phosphorylation pattern in S‐ and PET‐cells,3 nor in how this pattern changed on TPA exposure.Fluorescent activated cell sorting and karyotypic analysis revealed PET‐cells to be a hypotetraploid variant of S‐cells, with approximately 80 chromosomes, including a marker chromosome iso(1p) not found in the S‐cells.Identification of the biochemical lesion responsible for this TPA resistance in PET cells will provide clues concerning the mechanism of this important pathway for the induction of cell differentiation.
Association of inherited dysfibrinogenaemia and protein C deficiency in two unrelated families
Authors: Gandrille S. , Priollet P. , Capron L. , Roncato M. , Fiessinger J. N. , Aiach M. 
Published: March 2008

Summary An inherited association of dysfibrinogenaemia and protein C deficiency was found in three members of the same family. The propositus was a 48‐year‐old man who suffered from severe and rapidly complicated atherosclerosis of the aorta and lower limbs arteries, which perhaps suggests that the association of these two molecular abnormalities may have enhanced the thrombotic process. The abnormal fibrinogen had a reduced ability to bind thrombin which may be thrombogenic.We found the same inherited association of dysfibrinogenaemia and protein C deficiency in a patient with venous thrombosis. The functional abnormality of the fibrinogen, which could have been responsible for thrombosis, was delayed proteolysis by plasmin. Not only fibrinogen, but also fibrin clots were resistant to plasmic degradation. These observations raise two questions: (1) Is the association of a protein C deficiency with a dysfibrinogenaemia fortuitous or the result of a common mechanism? (2) Is there a link between an increased thrombotic tendency and either both of the defects of haemostasis that we have found, or only one of them?
Polynuclear iron complexes impair the function of polymorphonuclear granulocytes
Authors: Hoepelman I. M. , Jaarsma E. Y. , Verhoef J. , Marx J. J. M. 
Published: March 2008

Summary In a previous study we showed that the phagocytic function of non‐stimulated PMN was impaired after incubation with high concentrations (200 μm) of polynuclear Fe(III), probably as a result of continuous generation of small amounts of superoxide and subsequent formation of hydroxyl radicals (Van Asbeck et al, 1984b). Because polynuclear Fe(III) complexes may not be available for biological reactions we have studied the effects of polynuclear and mononuclear iron(III) on the PMN. Fe(III) in its polynuclear form (Fe: citrate 1:1) was deleterious for the phagocytic function of PMN, while the mononuclear form (Fe:citrate 1:20) was not toxic. Binding affinity of polynuclear Fe(III) for PMN was higher than of mononuclear Fe(III), and a considerable amount of bound Fe(III) was found in the cytosolic fraction of non‐stimulated PMN. Limit dilution analysis of polynuclear complexes revealed that concentrations as low as 25 μm Fe(III) significantly impaired phagocytic function. The molecular weight of these complexes is similar to that of the non‐transferrin plasma iron found in the serum of patients with iron overload.The toxic effects of small polynuclear non‐transferrin plasma Fe(III) complexes on PMN function may contribute to the development of infections in patients with iron overload.
Enrichment of haemopoietic progenitor cells from the marrow of patients with myelodysplasia
Authors: Baines Paul , Masters Gillian S. , Lush Christopher , Jacobs Allan 
Published: March 2008

SummaryMyeloid and erythroid progenitors from myelodysplastic marrows have been separated from accessory cell populations likely to influence their in‐vitro growth. Myeloid colony‐forming cells were enriched 23‐fold and erythroid progenitors 5‐7‐fold but, in both cases, retained their abnormal growth characteristics. After enrichment and removal of lymphocytes and monocytes, erythroid burst formation became markedly more dependent on the addition of 5637 bladder carcinoma conditioned medium as an exogenous source of haemopoietic growth factors. This suggests that lymphocytes and monocytes usually support erythropoiesis in cultures of myelodysplastic marrow and demonstrates that erythroid burst‐forming progenitor cells from myelodysplastic patients can respond to these populations in vitro. Haemopoietic failure in myelodysplasia appears to result from a defect within the preleukaemic clonogenic cell, rather than from an aberration in exogenous factors. The procedure outlined here can be used as a first step towards the isolation of these abnormal progenitors.
Polyclonal integration of HTLV‐I proviral DNA in lymphocytes from HTLV‐I seropositive individuals: an intermediate state between the healthy carrier state and smouldering ATL
Authors: Yamaguchi Kazunari , Kiyokawa Tetsuyuki , Nakada Kiyonobu , Yul Lee Song , Asou Norio , Ishii Toshinori , Sanada Isao , Seiki Motoharu , Yoshida Mitsuaki , Matutes Estela , Catovsky Daniel , Takatsuki Kiyoshi 
Published: March 2008

SummaryWe have studied 15 individuals (aged 14‐74 years) with antibodies to HTLV‐I in their serum and random integration of HTLV‐I proviral DNA in their peripheral blood lymphocytes. All but one of these patients suffered from a variety of non‐specific complaints which did not correspond to those of adult T‐cell leukaemia (ATL). All of them were born in Kyushu and Okinawa which are endemic areas for HTLV‐I infection; 25% of their family members were also seropositive for HTLV‐I. The only haematological abnormality in these patients was the presence of few atypical lymphoid cells in the peripheral blood. The CD4/CD8 ratios were normal but the proportion of Tac positive cells was slightly higher than normal.These individuals with polyclonal integration of HTLV‐I proviral DNA seem to represent an intermediate state between smouldering ATL (monoclonal integration) and healthy HTLV‐I carriers (with antibodies but no detectable HTLV‐I proviral DNA). Patients with this intermediate state of HTLV‐I infection may be at risk to progress to ATL. The natural history of HTLV‐I infection in humans leading to the development of ATL is reviewed in the light of these new findings.
Reversal of drug‐resistance in multiple myeloma with verapamil
Authors: Durie Brian G. M. , Dalton William S. 
Published: March 2008

Summary In vitro testing with a new doxorubicin resistant myeloma cell line revealed the reversal of drug resistance with as little as 100 ng/ml of verapamil (a calcium channel blocker), a dose easily achievable in humans. A first patient with IgGk Myeloma is presented in whom resistance to VAD (vincristine/doxorubicin infusion plus dexamethasone) chemotherapy was reversed with the administration of verapamil. A subsequent clinical study has been initiated. The potential for further evaluation of calcium channel blockers in multiple myeloma is discussed.