bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of liver disease on factors V, VIII and protein C
Authors: Kelly D. A. , O'Brien F. J. , Hutton R. A. , Tuddenham E. G. D. , Summerfield John A. , Sherlock S. 
Published: March 2008

Summary. The components of the factor VIII complex were estimated by immuno‐ and bioassays in 85 patients with liver disease. The plasma concentrations of the antigens were elevated in 65% (VIII:CAg) and in 76% (VIIIR:Ag) of patients while the biological activites were elevated in only 14% (VIII:C) and 15% (VIII:RiCof). There was no correlation with C‐reactive protein, used as a measure of an acute phase reaction (χ2=0·7; P=0·1); or with severity of liver disease as judged by prothrombin ratio (P=1·0) but highest values were observed in patients with cholestatic liver disease. Following parenteral vitamin K there was a significant fall in both the biological activity of VIIIC (36%) and of VIII:CAg (38%) in 13 vitamin K deficient patients (P<0·001) but no change in 23 vitamin K replete patients or in the VIIIR:Ag levels in either group.Factor V levels were lower in patients with parenchymal liver disease (0·54±0·1 units/ml, mean ±SEM, n=12; normal range 0·5–1·5 units/ml) than in patients with extrahepatic cholestasis who were vitamin K deficient (1·2 ± 0·1 units/ml, P<0·0001). The levels of protein C antigen, the vitamin K dependent protease which inactivates factors VIII:C and V, was at the lower end of the range in both groups (0·7±0·1, mean ±SEM, n= 18, normal range 0·74–1·4 units/ml). There was no significant change in either protein C antigen or factor V following vitamin K.The discrepancy between the biological activity of factor VIII and the antigen levels could represent accumulation of partially degraded factor VIII or production of a hypoactive form. There is no evidence that the reduction in VIIIC and VIII:CAg following vitamin K was mediated by protein C.
Leukaemic transformation of engrafted bone marrow cells
Authors: Smith Janice L. , Heerema Nyla A. , Provisor Arthur J. 
Published: March 2008

SummaryRecurrent leukaemia following bone marrow transplantation is most often due to the regrowth of original host leukaemia cells, but may also be due to the malignant transformation of normal donor marrow cells after transplantation into a leukaemia patient. We report the ninth case of malignant change in cells of donor origin in a 12‐year‐old boy who was originally diagnosed as having Ph1+ CML. He remained Ph1+ during lymphoid blast crisis. After transplantation with marrow from a cytogenetically normal sister, he relapsed to Ph1– ALL in the female donor cells. The marrow showed a mixed karyotype of 46,XX/46,XX,inv(9)(p12q12). It would appear that, haematologically, the patient showed different manifestations of the same disease state. Cytogenetically, however, the pre‐ and post‐transplant leukaemias were different.
Philadelphia chromosome‐negative chronic myelogenous leukaemia: a morphological reassessment
Authors: Pugh William C. , Pearson Marilyn , Vardiman James W. , Rowley Janet D. 
Published: March 2008

SummaryMorphological re‐examination of 25 cases classified as Ph1‐negative chronic myelogenous leukaemia (CML), with particular attention to the recent French‐American‐British (FAB) group proposals for the diagnosis of the myelodysplastic syndromes, led to reclassification of all but one of these cases. Upon review of pretreatment material, seven of the 25 cases (28%) were considered to represent myeloproliferative and reactive conditions other than CML. Of the remaining 18 cases, 17 (94%) were reclassified as myelodysplastic syndromes (MDS). These included one case of refractory anaemia (RA), three of refractory anaemia with excess of blasts (RAEB), four of RAEB in transformation (RAEBT), and nine of chronic myelomonocytic leukaemia (CMMoL). Haematological findings in these 17 patients were compared to those in 50 randomly selected patients with Ph1‐positive CML. Whereas an absolute basophilia in the peripheral blood was a nearly constant feature in the Ph1‐positive group, it was lacking in all but one of the patients with myelodysplastic syndromes. Differences in the pattern and degree of dysplasia were also noted. Only one of the 25 cases studied was considered morphologically and clinically indistinguishable from Ph1‐positive CML. It appears that Ph1‐negative CML constitutes a heterogeneous group of prognostically distinct disorders and the, in most instances, careful morphologic examination will permit precise classification.
Treatment of adult patients with idiopathic thrombocytopenic purpura with intravenous immunoglobulin: effects on circulating T cell subsets and PWM‐induced antibody synthesis in vitro
Authors: Dammacco F. , Iodice G. , Campobasso N. 
Published: March 2008

Summary. Eight adult patients with idiopathic thrombocytopenic purpura (ITP) were given two 5‐d courses of intermediate (250 mg/kg body weight/d) to high dose (400 mg/kg body weight/d) intravenous infusions of human plasmin‐cleaved Ig, at 15–30 d intervals. Three patients also were given single booster infusions (400 mg/kg body weight for 1 d) of a different preparation, S‐sulfonated Ig. As expected, significant though transient rises in the platelet count were consistently observed in all patients. The mean platelet count increase was 95 600/mm3 after the first course, and 143 500/mm3 after the second course. Similar effects of lower magnitude were obtained several times in the patients given single booster doses. In three patients, platelet‐bound IgG levels were decreased in association with Ig therapy.Phenotypic analysis of T cell subsets before starting Ig therapy and at the end of the second high dose course of intravenous Ig treatment revealed significant reductions in the proportion of T4 + lymphocytes in five patients and relative increases in the percentage of T8 + cells after therapy. As the overall proportion of T3 + cells remained unchanged, the T4 +/T8 + ratio was therefore decreased. The total number of circulating lymphocytes was also decreased following therapy. In addition, PWM‐driven Ig biosynthesis in vitro was significantly impaired after therapy in most patients, the capacity to synthesize IgG being mainly affected. It is concluded that, in addition to the reported transient blockade of the reticuloendothelial system, non‐specific suppression of polyclonal Ig biosynthesis induced by the high dose Ig infusions also contributes to the net increase in platelet count.
Acute lymphoblastic leukaemia in a child with familial Pelger‐Huet anomaly
Authors: Oneson Ruth , Sabio Hernan , Innes Donald J. 
Published: March 2008

SummaryA case of familial Pelger‐Huet anomaly in a 3‐year‐old boy with acute lymphoblastic leukaemia is described. This unique association was investigated through serial observations of the peripheral blood smear and bone marrow obtained during the child's treatment with chemotherapy. The average lobe index (ALI) of neutrophils was 1·42 with no three‐lobed forms at the time of the initial diagnosis. During antimetabolite maintenance therapy with 6‐mercaptopurine and methotrexate the ALI was 1·87 and three‐lobed forms were present. The behaviour of the P‐HA cells to heat induced radial hypersegmentation of the nucleus was examined in other family members. The mechanism by which heat and folate deficiency induce neutrophil segmentation is preserved in the familial Pelger‐Huet anomaly.
Heterogeneity of IgG1 monoclonal anti‐Rh(D): an investigation using ADCC and macrophage binding assays
Authors: Armstrong Sylvia S. , Wiener Edith , Garner S. F. , Urbaniak S. J. , Contreras Marcela 
Published: March 2008

SummaryThree monoclonal IgG1 anti‐Rh(D), UCH D4, ARC 7D5 and UKTS FC3, produced by Epstein‐Barr virus transformed cells from Rh(D)‐sensitized individuals, were compared with polyclonal single donor anti‐D sera and therapeutic immunoglobulin preparations in antibody dependent cellular cytotoxicity (ADCC) and macrophage binding tests. When assayed at equal anti‐D concentrations monoclonal antibodies varied considerably in their ADCC and macrophage binding activities: only UKTS FC3 showed significant activity in both assays, but these were substantially lower than those of the polyclonal anti‐D sera and immunoglobulins. When examined in different combinations the monoclonal antibodies showed little synergism in mediating red cell destruction by the effector cells. Factors which might contribute to the diverse ADCC and macrophage binding activities of the monoclonal anti‐Ds of the same IgG subclass are discussed.
Platelet antibodies in systemic lupus erythematosus
Authors: Kaplan C. , Champeix P. , Blanchard D. , Muller J. Y. , Cartron J. P. 
Published: March 2008

Summary. In systemic lupus erythematosus (SLE), the precise cause of the thrombocytopenia is unknown. Since platelet associated IgG is increased in many patients, it has been suggested that the destruction of platelets might be dependent on specific antibodies.In nine patients with SLE, platelet associated immunoglobulins were found together with free serum antibody which bound to platelets from all normal subjects.Using an immunoblotting technique with membrane proteins from normal platelets incubated with patient sera, target antigens were localized on a band of mol wt 108 000 in two cases (B. and N.) and on a band of mol wt 66 000 in a third (M.). When the same technique was applied to autologous platelets of patient N., autoantibody binding to the protein of mol wt 108 000 was demonstrated. The antigenic determinants were not removed from the platelets by enzyme treatment or by disulphide bond reduction, and were localized in the cytoplasmic fraction of the platelets.
Clinical and cytogenetic features of familial erythroleukaemia
Authors: Lee Edward J. , Schiffer Charles A. , Misawa Shinichi , Testa Joseph R. 
Published: March 2008

Summary.A family is described in which six members developed acute nonlymphocytic leukaemia (ANLL) over the past 1 5 years, all morphologically FAB M6. Five affected individuals (ages 54‐73) are members of a single sibship, the sixth (age 31) was the son of one of the affected sibs. The family lives in a rural area, and no environmental hazard has been identified. One of the six patients never resided in the same geographic area as the others. Three patients with leukaemia died without chemotherapy, two died shortly after the initiation of chemotherapy and the most recent patient never achieved remission, surviving 10 months. Bone marrow specimens from the two most recent patients were analysed for cytogenetic abnormalities using chromosome banding techniques. In addition, skin fibroblasts were examined in a single patient. The fibroblasts had a normal karyotype. Bone marrow cells from both patients had complex abnormalities. Some similarities were observed, including: (1) hypodiploidy; (2) loss of one chromosome 20; (3) the presence of multiple marker chromosomes. In each case one marker appeared to involve the‘missing’no. 20 with an alteration of the long arm—loss (20q —) in one patient and gain (20q +) in the other. Peripheral blood lymphocytes were grown in folate deficient medium, but no evidence for folate sensitive fragile sites was found. Marrow chromosomes from a third leukaemic sibling were examined without banding techniques in 1976 and the karyotype was 45.XY, — 18, — F(19 or 20), ‐I‐marker. No specific cytogenetic finding was common to the three patients studied except for the loss of an F group chromosome. This family is unique in the literature with six cases of familial leukaemia of the same morphologic subtype, and the cytogenetic findings suggest that loss or rearrangement of part of the long arm of a single chromosome 20 may have occurred in each of the three patients examined.
Association of thalassaemia intermedia with a beta‐globin gene haplotype
Authors: Thein S. L. , Wainscoat J. S. , Sampietro M. , Old J. M. , Cappellini D. , Fiorelli G. , Modell B. , Weatherall D. J. 
Published: March 2008

Summary.We have identified 14 Asian patients with homozygous β° thalassaemia who had a mild clinical disorder related to an augmented production of haemoglobin F. None of their parents had an elevated level of Hb F. Restriction fragment length polymorphism analysis of the β‐globin cluster of these patients and a control group of Asian thalassaemia major patients showed that 6/14 of the thalassaemia intermedia patients were homozgyous for a particular 5′β‐globin haplotype (−+−++), in contrast to 1/42 of the thalassaemia major patients. Furthermore, the —+—++β haplotype is also associated with amelioration of disease severity in β thalassaemia in an Italian population. This β haplotype is linked to a DNA sequence variation 5′ (at position — 158) to the cγ globin gene which can be detected by the presence (+) of an Xmn I restriction enzyme site. The possible role of the Xmn I‐γ polymorphism in relation to this variant HPFH is discussed. We conclude that much of the observed clinical variability of β thalassaemia can now be explained by the inheritance of β thalassaemia chromosomes with different propensities for fetal haemoglobin production.
Depressed fibrinolysis in patients with acute leukaemia
Authors: Guarini A. , Mussoni L. , Gugliotta L. , Chetti L. , Niewiarowski T. , Catani L. , Macchi S. , Donati M. B. , Tura S. 
Published: March 2008

SummaryThe fibrinolytic system was studied in 46 patients with acute leukaemia at diagnosis. Untreated patients (with the sole exception of the M3 subgroup) showed an inhibition of fibrinolytic activity, measured by the euglobulin lysis time and area. This inhibition was accompanied by reduced t‐PA antigen and t‐PA inhibitor activity. No correlation was found between the above‐mentioned fibrinolytic parameters and the biochemical haematological values considered, nor with clinical and/or laboratory features of DIC. fever, liver failure. The decrease in immunological plasminogen and functional α2‐antiplasmin, showed a significant correlation with the presence of clinical and/or laboratory signs of DIC, as diagnosed on the basis of concomitant increase in fibrin monomers, plasmatic fibrinopeptide A and serum FDP.
Platelet peroxidase‐positive blast cells in transient myeloproliferative disorder with Down's syndrome
Authors: Suda Junko , Eguchi Mitsuoki , Ozawa Takebumi , Furukawa Toshiharu , Hayashi Yasuhide , Kojima Seiji , Maeda Hiroo , Tadokoro Kenji , Sato Yuko , Miura Yasusada , Ohara Akira , Suda Toshio 
Published: March 2008

SummaryTransient myeloproliferative disorder accompanied by Down's syndrome has been characterized as exhibiting self‐limiting haematological abnormalities. We studied six patients suffering from this disorder in order to clarify the biological nature of their blast cells. Metaphases of leucocytes stimulated with phytohaemagglutinin (PHA) showed trisomy 21 in all patients except one. The exception was constitutionally trisomy 21 mosaic (46, XY = 89/ 47,XY. + 21 = 11). However, metaphases from the peripheral blood cells (blast cells: 70%) without PHA stimulation showed exclusively trisomy 21. Simultaneous examination for morphology and chromosomal analysis on single colonies revealed that granulocyte‐macrophage (GM) colonies and an erythroid colony contained only cells with the trisomy 21 karyotype.The blast cells showed positive reactions for platelet peroxidase (PPO) and with monoclonal antibodies against platelet‐megakaryocyte antigen (TP 80 and TP 82). In methylcellulose and liquid culture systems, high plating efficiencies were observed, and mainly mature basophils containing histamine developed in the presence of PHA‐stimulated leucocyte conditioned medium (PHA‐LCM). In vivo, mature neutrophils, basophils, eosinophils or megakaryocytes coexisted with PPO‐positive blast cells in the peripheral blood of some patients with this disorder.These findings suggest that transient myeloproliferative disorder is characterized by a proliferation of PPO‐positive blast cells with trisomy 21, although some heterogeneity may be seen.
Reduction of membrane band 7 and activation of volume stimulated (K+, Cl−)‐cotransport in a case of congenital stomatocytosis
Authors: Morlé L. , Pothier B. , Alloisio N. , Féo C. , Garay R. , Bost M. , Delaunay J. 
Published: March 2008

SummaryWe report on a case of congenital stomatocytosis in a French boy presenting with a haemolytic anaemia requiring splenectomy at the age of 6. The red cells included 15‐20% stomatocytes and displayed a marked increase of volume. Their osmotic resistance and density were reduced; however, their deformability was unaltered in isotonicity. Erythrocyte Na+ was high (27 mEq/1) and K+ low (65 mEq/1). The newly described (K+, Cl−)‐cotransporter normally triggered by hypo‐osmotic stress, was activated to maximal capacity. Membrane band 7 was reduced by 72%. From anamnestic data, the condition appears to have been transmitted by the father. The mother proved to be strictly normal on clinical, morphological, osmotic and biochemical bases. We suggest that the partly missing band 7 may play an important role in the genesis of stomatocytosis.
AML associated with previous cytotoxic therapy, MDS or myeloproliferative disorders: results from the MRC's 9th AML trial
Authors: Hoyle Christine F. , Bastos Marcosde , Wheatley Keith , Sherrington P. D. , Fischer P. J. , Rees J. K. H. , Gray Richard , Hayhoe F. G. J. 
Published: March 2008

Summary. The outcome of treatment with standard first line therapy of 66 patients with acute myeloid leukaemia (AML) secondary to preceding chemotherapy (Group 1), a myelo‐dysplastic state (Group 2) or a myeloproliferative disorder (Group 3) was analysed in relation to the preceding disorder, the cytogenetic pattern where available, and the cytology and cytochemistry of blood and bone marrow.The complete remission (CR) rate for the secondary AMLs was 36% (24/66), with 24% (16/66) dying in the induction period and 39% (26/66) having resistant disease. The CR rate was 25% (5/20) for Group 1, 42% (15/36) for Group 2, and 40% (4/10) for Group 3. Even after allowance for the generally older age of the secondary AML patients, they still had a significantly poorer CR rate than the de novo AMLs (P= 0.0004). The lower CR rate was chiefly due to resistant disease. Despite this, overall survival was not significantly worse for the secondary AML patients (P= 0.15). For the 36% that achieved remission, remission duration appeared similar to that of de novo cases.Of 62 cases with adequate cytology, 38 (61%) had evidence of erythroid and/or megakaryocytic dysplasia with a CR rate of 32% (12/38). The CR rate of these multineage leukaemias was not significantly different from that of the 24 (39%) who showed granulocyte/monocyte precursor involvement only, 42% (10) of whom achieved CR. The presence of features of differentiation within blast cells such as Auer rods or sudanophilia (> 50% positive blasts) was associated with a higher remission rate 47% (18/38) than that of poorly differentiated cases 17% (3/18) (P= 0.04) and thus appeared to be a more important determinant of CR achievement than was lineage involvement.Cases with a normal karyotype had a 33% (7/21) CR rate, while those with chromosomal abnormalities had a 37% (9/24) CR rate. Only 12 of the 45 cases with adequate cytogenetic analysis showed deletions or monosomies involving chromosomes 5 or 7, and seven of these were in Group 1.
The DNA deletion in an Indian δβ‐thalassaemia begins one kilobase from the Aγ globin gene and ends in an LI repetitive sequence
Authors: Mishima N. , Landman H. , Huisman T. H. J. , Gilman J. G. 
Published: March 2008

SummaryHigh fetal haemoglobin levels of 5–15% are present in adult heterozygotes for δβ‐thalassaemia as the result of large deletions of DNA. We have cloned DNA spanning the deletion breakpoint for a new Indian δβ‐thalassaemia associated with mild anaemia. The 5’ breakpoint is at 42151 of GenBank file HUMHBB, which is about 1 kb 3’ of the Aγ globin gene poly A site at 41003. On the 3’ side of the breakpoint, the sequence is homologous to LI (KpnI) repetitive DNA located 3.6–10 kb 3’ of the β‐globin gene: Indian δβ‐thalassaemia DNA is 74% homologous to the inverted complement of HUMHBB from 69849 to 70020, followed by a region 78% homologous to the direct sequence of HUMHBB from 70534 to 71010. The precise location of the 3’ endpoint of this deletion has not been determined, but it is within LI sequences located more than 10 kb 3’ of the β‐globin gene.
Favourable outcome of patients older than 40 years of age after transplantation with marrow grafts depleted of lymphocytes by counterflow centrifugation
Authors: Bär B. M. A. M. , Witte T. De , Schattenberg A. , Boezeman J. , Hoogenhout J. 
Published: March 2008

SummaryNineteen patients with a median age of 43 years (range 40–48) were transplanted for acute myelogenous leukaemia (AML), refractory anaemia with excess of blasts in transformation (RAEBt), acute lymphoblastic leukaemia (ALL) in first complete remission, multiple myeloma, and chronic myelogenous leukaemia (CML) in chronic or accelerated phase. Their outcome was compared with that of 35 patients with a median age of 34 years (range 30–39), and a group of patients with age younger than 30 years (median 24; range 16–29) transplanted for the same indications. Donors were human leucocyte antigen (HLA)‐identical, mixed lymphocyte culture (MLC) negative siblings. All marrow grafts were depleted of lymphocytes by counterflow centrifugation. The estimated event‐free survival at 3 years after allogeneic bone marrow transplantation was 60.7% for patients with age > 39 years, 57.8% for patients with age <30, and 43.0% for the intermediate age group (P>0.3). The estimated transplant‐related mortality showed no tendency to increase with older age of recipients. The incidence of acute GVHD>grade 1 was 15.7% in patients with age > 39 years, 9.5% in patients younger than 30 years, and 23% in the intermediate age group. The incidence of chronic GVHD was higher in the older patients (39% compared to 24% in patients younger than 30 years, 19% in the intermediate age group). Chronic GVHD resolved completely in five out of seven patients aged 40 years or more.Reduction of the incidence of acute graft‐versus‐host disease by physical lymphocyte depletion allows allogeneic bone marrow transplantation for patients aged 40–50 years without increase of transplant‐related mortality resulting in similar event‐free survival in patients older than 40 years compared to those younger than 40 years.