bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of Platelet Production in Mice made Thrombocytopenic by Hypoxia and by Platelet Specific Antisera
Authors: McDonald T. P.
Published: March 2008

Summary. Previous experiments have shown that hypoxia causes thrombocytopenia in mice. In an attempt to define the recovery phase, mice were enclosed in hypoxia chambers for 14 d and platelet counts, total circulating platelet counts (TCPC) and masses (TCPM), platelet sizes, and %35S incorporation into platelets were determined over the next 8 d while the mice were kept at ambient O2 levels. For comparison, untreated mice and mice made thrombocytopenic by injection of rabbit anti‐mouse‐platelet serum (RAMPS) were used. Both 14 d of hypoxia and RAMPS treatment resulted in severe thrombocytopenia. TCPC and TCPM were similar in both exhypoxic and RAMPS‐injected mice. However, the platelet count recovery pattern of exhypoxic‐thrombocytopenic mice did not show the rebound‐thrombocytosis which was characteristic of RAMPS‐induced thrombocytopenia, apparently because of dilution of platelets by increased blood volumes. Average platelet sizes were larger than normal 2 d posthypoxia or after RAMPS‐treatment, followed by a decline toward normal; platelets from exhypoxic mice, however, remained larger. Per cent 35S incorporation into platelets was lower in exhypoxic mice than in RAMPS‐treated mice; lower numbers of megakaryocytes were observed immediately after removal from hypoxia followed by an increase in number and size by 2 d later. Also, thrombopoietin was detected in plasma of RAMPS‐treated mice, but not in plasma of exhypoxic‐thrombocytopenic mice. Therefore, it seems possible that hypoxia reduced the numbers of megakaryocytes, resulting in depressed thrombocytopoiesis of mice at the time of removal from hypoxic atmospheres.
Monocyte‐Induced Increase in Osmotic Fragility of Human Red Cells Sensitized with Anti‐D Alloantibodies
Authors: Fleer A. , Koopman Marion G. , von dem Borne A. E. G. Kr. , Engelfriet C. P.
Published: March 2008

Summary.

The mechanism by which human monocytes increase the osmotic fragility of red cells sensitized with Rhesus alloantibodies anti‐D was studied in vitro. Both the increase in osmotic fragility and the lysis of red cells by monocytes were enhanced by cytochalasin B and were inhibited by hydrocortisone. These effects were similar to the effects of these agents on lysosomal enzyme release by monocytes. However, hydrocortisone was completely ineffective when added I h after mixing monocytes and sensitized red cells. This indicates that the damage responsible for the fragility increase and lysis is completed within I h and suggests that it is due to lysosomal enzymes released by the monocytes. Since for the full expression of the osmotic fragility increase and lysis an incubation time much longer than I h is required, it appears that the latter phenomena are the non‐specific sequelae of damage inflicted upon the red cell by released lysosomal enzymes.
IgM Inhibitors of the Contact Activation Phase of Coagulation in Chlorpromazine‐ Treated Patients
Authors: Zucker Stanley , Zarrabi Mohammad H. , Romano Gail S. , Miler Frederick
Published: March 2008

Summary. In this report we have described three patients with chronic schizophrenia on long‐term chlorpromazine therapy who developed asymptomatic IgM inhibitors of the intrinsic phase of blood coagulation. The anticoagulant resulted in decreased measurements of all of the plasma clotting factors in the intrinsic pathway (factors VIII, IX, XI, XII, Fletcher factor and Fitzgerald factor). Using crude coagulation reagents, the serum of these patients interfered with the clot promoting activity of contact product. To determine the relationship between drug therapy and these IgM inhibitors, we have studied nine additional schizophrenic patients on long‐term chlorpromazine therapy. All nine chlorpromazine‐treated patients had significantly increased levels of serum IgM and asymptomatic inhibitors of coagulation. We conclude that long‐term high‐dose chlorpromazine treatment of schizophrenic patients results in an increased concentration of IgM which has inhibitory activity in the contact phase of blood coagulation.
An Artificial ‘Haemophilic’ Plasma for One‐Stage Factor‐VIII Assay
Authors: Chantarangkul V. , Ingram G. I. C. , Thorn M. B. , Darby S. C.
Published: March 2008

Summary. An ‘artificial’plasma for one‐stage factor‐VIII assays is made by incubating human plasma with EDTA, to destroy factor VIII, and afterwards removing the anticoagulant by dialysis. Bovine factor V is then added to a given level. In the assay, contact activation is controlled by adding contact product. It was confirmed that factor‐VIII activity was destroyed and that the EDTA was freely dialysable. The fibrinogen in the treated plasma clotted normally with thrombin. Likely variation in the factor‐V activity was found not to be critical. The concentration of fibrinogen and other factors was adequate. Variation between batches was small. The artificial plasma yielded assay results closely comparable to haemophilic plasma in samples with factor‐VIII activities in the range 0.01–20.0 iu/ml; the mean results in the artificial system were estimated to be 0.997 x those in haemophilic plasma, with a 95% confidence interval of 0.901‐1.103. Biological variability in individual assays was smaller in the artificial system than when haemophilic plasma was used. Instability at the bench was more often detected in the artificial system than in haemophilic plasma assays, but the effect was eliminated from the results by obtaining duplicated readings in a balanced order.
Platelet Storage Pool Deficiency and Prostaglandin Synthesis in Chronic Granulocytic Leukaemia
Authors: Gerrard J. M. , Stoddard S. F. , Shapiro R. S. , Coccia P. F. , Ramsay N. K. C. , Nesbit M. E. , Rao G. H. R. , Krivit W. , White J. G.
Published: March 2008

Summary. Platelet function was evaluated in eight patients with chronic granulocytic leukaemia (CGL), seven Ph1 positive and one Ph1 negative. Seven of the eight patients’platelets had an absence of the second wave of adrenaline induced aggregation on at least one occasion, while five had impaired collagen aggregation. The platelets of all seven patients with abnormal responses to adrenaline, aggregated with arachidonic acid, thus ruling out a cyclo‐oxygenase deficiency. A marked decrease in the ADP, serotonin, and dense body content of platelets was found in all five patients evaluated. Mixtures of CGL patient platelets with platelets from normal donors who had ingested aspirin gave a normal biphasic response to adrenaline. Normal release of the storage pool contents from aspirin treated platelets was shown by stirring a mixture of CGL platelets and 14C‐serotonin labelled aspirin treated platelets with adrenaline. The CGL platelets alone or in the mixture produced malondialdehyde in response to adrenaline. These experimental results suggest that CGL platelets have a storage pool deficiency but can synthesize prostaglandins and thromboxanes in response to arachidonic acid and adrenaline.
Investigation of the Role of Arachidonic Acid in Platelet Function and Mechanisms for Suppression of Prostaglandin Biosynthesis
Authors: Akbar Huzoor , Ardlie Neville G.
Published: March 2008

Summary. The effects of two hypolipidaemic agents (clofibrate and halofenate free acid, HFA) and aspirin on the release of the contents of different granules and on cyclic endoperoxide formation induced by sodium arachidonate and thrombin, were investigated. Aspirin and HFA completely blocked aggregation by arachidonate whereas clofibrate potentiated aggregation. Aspirin and HFA were able to inhibit the platelet shape change caused by arachidonate. Arachidonate at low concentrations released [3H]5HT; at a higher concentration there was release of β‐glucuronidase accompanied by loss of cytoplasmic LDH into the supernatant, indicating lysis. Platelets converted exogenous sodium arachidonate to malonyldial‐dehyde (MDA), the conversion being completely inhibited by aspirin and HFA but not by clofibrate. Thrombin which is believed to provide endogenous arachidonic acid for conversion to endoperoxides, caused MDA formation and this was inhibited by clofibrate as well as by HFA and aspirin. Despite inhibition of endoperoxide arachidonate were still able to release the contents of platelet granules. These findings suggest that all the effects on platelets of low concentrations of exogenous arachidonate may be due to its conversion to prostaglandin endoperoxides whereas the release reaction initiated by higher concentrations of thrombin or exogenous arachidonate involves endoperoxide‐dependent and independent mechanisms. Moreover, the mechanisms of release from dense and α‐granules of platelets may be similar in some respects. It is concluded that HFA, like aspirin, suppresses biosynthesis of endoperoxides by inhibiting formation of arachidonic acid from phospholipids.
Erythrokinetic Studies in Hairy‐Cell Leukaemia
Authors: Castro‐Malaspina Hugo , Najean Yves , Flandrin Georges
Published: March 2008

Summary. Erythrokinetics were studied in 29 patients with hairy‐cell leukaemia. In all cases there was an increase in plasma volume, closely correlated to the size of the spleen, indicating that the true degree of anaemia can only be appreciated by red cell volume measurement. Moderately increased haemolysis was observed in most cases, which did not correlate with the spleen size. Simultaneous study of autologous and isologous red cell life‐span suggested an extra‐corpuscular mechanism for the haemolysis in most patients.

A quantitative erythropoietic defect, either relative or absolute, was found in half the cases, without any qualitative defect. Only one case showed erythroid metaplasia of the spleen. Thus marrow failure appears to be largely responsible for the anaemia and granulocytopenia in hairy‐cell leukaemia. A clear correlation was shown between the short‐term prognosis after splenectomy and the degree of hypersplenism. However, long‐term survival correlated chiefly with the degree of bone marrow failure, whether splenectomy had been carried out or not. The results indicate that isotope studies in hairy‐cell leukaemia are useful both in determining the best form of treatment and predicting survival.
Splenectomy in Patients with Agnogenic Myeloid Metaplasia: an Analysis of 321 Published Cases
Authors: Benbassat J. , Penchas S. , Ligumski M.
Published: March 2008

Summary. The available data on 321 published cases of splenectomy in agnogenic myeloid metaplasia were reviewed. Anaemia and thrombopenia were the most common indications for this operation. Patients reported after 1940 had a median postoperative survival of 13 months. Their postoperative mortality was 7.5% after 2 d and 25.7% after 3 months. The postoperative mortality was significantly higher when the weight of the spleen exceeded 2000 g, or in patients with platelet count less than 70 × 109/l. The most common causes of death were infections (34.4%), cardiac or thromboembolic events (26.4%) and haemorrhage (17.6%). Leukaemic transformation was reported in 11.2% of the cases.
Nonrecessively Transmitted Nonspherocytic Hereditary Haemolytic Anaemia Associated with Increased Red Cell Glutathione
Authors: Valentine William N. , Paglia Donald E.
Published: March 2008

Summary. Hereditary haemolytic anaemia not associated with spherocytosis, ovalocytosis, stomatocytosis or haemoglobinopathy was observed in three members of a kindred. There were no demonstrable abnormalities of enzymes of the Embden‐Myerhof pathway, the hexosemonophosphate shunt, or of a variety of non‐glycolytic enzymatic activities assayed in patient erythrocytes. In each case, red cell glutathione was increased in concentration three to six standard deviations above our normal mean. Erythrocyte glutathione was normally stable and all sulfhydryl reacting material was shown by specific enzyme assays to represent either reduced (97%) or oxidized (3%) glutathione. No abnormality in active transport of oxidized glutathione was demonstrable in the red cells. This syndrome of unknown aetiology was transmitted in autosomally dominant fashion or, alternatively, as a possibly x‐chromosome linked disorder. Existing data did not permit the differentiation of these two possibilities.
Reduced Number of Peripheral Blood Granulocytic Progenitor Cells in Patients with Down's Syndrome
Authors: Standen Graham , Philip Mark A. , Fletcher John
Published: March 2008

Summary. The number of granulocytic progenitor cells (colony forming units in culture: CFUc) in the blood of patients with Down's syndrome was found to be reduced by 73.2% when compared to a group of age and sex matched controls. However, the blood CFUc of the Down's syndrome patients and the controls showed similar sensitivity to hydroxyurea which suggests that the low number of progenitor cells in Down's syndrome is not compensated by a marked increase in their cellular proliferation. The colony size distributions were similar for both the patients and the controls and, in addition, repeated assays at various intervals revealed no marked fluctuation in the number of blood CFUc in either group. The significance of the reduced number of circulating CFUc in Down's syndrome in relation to the known susceptibility of such patients to leukaemia is discussed.
Successful Maintenance Immunotherapy by BCG of Non‐Hodgkin's Malignant Lymphomas: Results of a Controlled Trial*
Authors: Hœrni B. , Durand M. , Richaud P. , De Mascarel A. , Hœrni‐Simon G. , Chauvergne J. , Lagarde C.
Published: March 2008

Summary. Forty‐eight patients less than 65 years old, suffering non‐Hodgkin's malignant lymphomas with one or more criteria of poor prognosis, were priorly placed in complete remission by an association of chemo+radio+chemotherapy. They were then randomized to receive either BCG in weekly scarifications for 3 years or no further treatment. Five patients were excluded (four after pathological reassessment); 43 are thus evaluable. There were 13 relapses out of 23 control patients and three relapses out of 20 treated patients (0.01<P<0.025). This differenceis more distinct for clinical stages I and II (0.01<P<0.025) than for stages III and IV (not significant). Eight patients died in the control group whereas there was only one death in the treated group (0.025<P<0.05). These results indicate that BCG is useful in maintaining remission in about 40% of the cases and also in increasing their survival, especially in patients with clinical stages I or II.
Haemoglobin Lepore Trait: Haematological and Structural Studies on the Italian Population
Authors: Marinucci M. , Mavilio F. , Massa A. , Gabbianelli M. , Fontanarosa P. P. , Samoggia P. , Tentori L.
Published: March 2008

Summary. Haematological data on 59 heterozygotes for haemoglobin (Hb) Lepore and 10 double heterozygotes for Hb Lepore and β thalassaemia from 36 Italian families are reported. The red cell indices are defined and compared with those of groups of non‐thalassaemic and β thalassaemic subjects of comparable number, age and sex distribution. The relative level of each haemoglobin fraction and the absolute production of single polypeptide chains are calculated in order to compare the expression of the non‐α chain genes in Hb Lepore trait and β thalassaemia. Structural studies demonstrate that the haemoglobin Lepore is of the Boston type (δ87β116) in all subjects, confirming that this type of fusion variant is probably the only one which occurs in Mediterranean populations. The distribution and incidence of the Lepore haemoglobinopathy are discussed.
Y Chromosome Loss in Childhood Leukaemias
Authors: Padre‐Mendoza Teresita , Farnes Patricia , Barker Barbara E. , Smith Peter S. , Forman Edwin N.
Published: March 2008

Summary. During the past 3½ years cytogenetic studies have been performed on all children with leukaemia prior to treatment. Loss of the Y chromosome documented by chromosome banding techniques, was observed in bone marrow blast cells from two of 11 consecutive male children. One patient had acute myeloblastic leukaemia of t(8;21) type. The other patient was diagnosed as acute lymphoblastic leukaemia. Our studies provide evidence that Y loss occurs in childhood leukaemias and is not necessarily related to an ageing process as suggested by others. Furthermore, this study demonstrates that Y loss can occur as a sole abnormality in non‐myeloid leukaemia.
Diamond‐Blackfan Syndrome: Evidence for T‐Cell Mediated Suppression of Erythroid Development and a Serum Blocking Factor Associated with Remission
Authors: Steinberg Martin H. , Coleman Mary F. , Pennebaker James B.
Published: March 2008

Summary. Diamond‐Blackfan syndrome may be a disorder of cellular immunity. Lymphocytes from some patients are capable of suppressing erythropoiesis in cultures of normal bone marrow.

We studied two adults with this disorder, both in complete unmaintained remission, using a technique for cloning peripheral blood erythroid precursors (BFU‐E) in culture. The BFU‐E may be an early, erythropoietin sensitive, erythroid committed stem cell. Under culture conditions, which employ fetal calf serum, neither patients cells formed normal numbers of erythroid colonies. Controls yielded 15.3 ± 5.2 BFU‐E/2.5 × io5 mononuclear cells. Culture of patients cells using autologous serum, promoted more normal growth of BFU‐E (21.4 ± 6.9 and 7.3 ± 2.3 BFU‐E/2.5 × io5 cells). Patient mononuclear cells, cocultured with normal cells, generally suppressed BFU‐E generation. Cocultures of normals were not inhibitory. Removal of T‐lymphocytes from patient mononuclear cells permitted normal growth of BFU‐E in coculture with controls. T‐cells depleted Diamond‐Blackfan mononuclear cells showed BFU‐E formation in fetal calf and autologous serum. Diamond‐Blackfan T‐cells inhibited BFU‐E formation by normal mononuclear cells.

The cellular defect in Diamond‐Blackfan syndrome persists during complete remission and may be mediated by lymphocytes. The development of a serum factor which blocks the suppressive effects on erythroid precursors of a subpopulation of autologous T‐cells may be responsible for the development of remission in our patients.
Subtypes of i Demonstrated by the Use of Atypical Ii Cell Types and Inhibition Studies
Authors: Dzierzkowa‐Borodej W. , Voak D.
Published: March 2008

Summary. Haemagglutination, absorption and elution studies with several anti‐i sera and atypical Ii red cell types and Oh cells were carried out and three subtypes of specificity were demonstrated. The fourth i subtype was demonstrated by an inhibition method using human scrum and amniotic fluid as a source of i substance.
Hereditary Stomatocytosis: Association of Low 2,3‐Diphosphoglycerate with Increased Cation Pumping by the Red Cell
Authors: Wiley J. S. , Cooper R. A. , Adachi K. , Asakura T.
Published: March 2008

Summary. The levels of glycolytic intermediates have been measured in red cells from patients with both overhydrated and dehydrated varieties of the hereditary stomatocytosis syndrome. Red cell 2,3‐diphosphoglycerate was reduced by 33% below normal in all patients with either stomatocyte or target cell morphologies (i.e. over or under hydrated varieties respectively). The relative decrement in 2,3‐diphosphoglycerate was even greater when abnormal cells were compared with control cells with similar reticulocytosis. Red cell ADP concentrations in stomatocytosis were significantly increased above normal but ATP concentrations were not significantly changed. Whole blood oxygen affinity in stomatocytosis was increased in proportion to the lowered content of diphosphoglycerate. Some new parameters of membrane transport in hereditary stomatocytosis have been measured. Platelet K+ and Na+ concentrations and platelet K+ permeability were normal in stomatocytosis. The number of 3H‐uridine transport sites in stomatocytes were increased by 9‐39% above normal and this increment was the same as the increment in red cell lipids (0‐38%). Hereditary stomatocytes contain 2‐10‐fold more cation pumps than normal and the increased active cation pumping may explain the high ADP, the low 2,3‐diphosphoglycerate concentration and the increased oxygen affinity in this syndrome.
Mechanism of the Decreased Erythropoiesis in the Water Deprived Rat
Authors: Giglio J. M. , Alippi R. M. , Barceló A. C. , Bozzini C. E.
Published: March 2008

Radioiron uptake by erythrocytes, metabolic rate, erythropoietin formation during hypoxia and erythroid responsiveness to exogenous erythropoietin were determined in both starved and water deprived rats. The feed intake showed a marked and progressive reduction during water deprivation. The metabolic rates of rats deprived of either food of water declined progressively showing a 40% reduction 5 d after water deprivation or starvation began. At this time, the 24 h red blood cells 59Fe incorporation was 85% lower in both starved and dehydrated rats than in normal rats. Plasma erythropoietin levels in response to hypoxia were approximately 50% decreased in both starved and dehydrated rats. Both polycythaemic starved and polycythaemic water deprived rats injected with human urinary erythropoietin showed a 75% decrease in 59Fe incorporation into erythrocytes when compared to control rats.

It is suggested that depression of erythropoiesis during water deprivation in the rat depends on a reduced sensitivity to erythropoietin, possibly associated with decreased production of the hormone. Since water deprived rats drastically reduce feed intake it is suggested that secondary starvation is the principal cause of the decreased erythropoiesis induced in the rat by water deprivation.
t(8;14) Translocation in a Burkitt's Type of Lymphoblastic Leukaemia (L3)
Authors: Berger R. , Bernheim A. , Brouet J. C. , Daniel† M. T. , Flandrin G.
Published: March 2008

Summary. Cytogenetic findings on five patients with ALL Burkitt's type are reported. A t(8;14) (q23;q32) translocation identical to that found in Burkitt's lymphoma cells was found in each case. The relationship between ALL, L3 type and Burkitt's tumours is discussed.
Studies on the Mechanism of Ristocetin‐induced Platelet Aggregation: Binding of Factor VIII to Platelets
Authors: Schneider‐Trip M. D. , Jenkins C. S. P. , Kahlé L. H. , Sturk A. , Ten Cate J. W.
Published: March 2008

Summary. The effect of ristocetin on the binding of [125I]factor VIII to platelets was studied. High and low affinity F. VIII binding sites exist on platelets. The high affinity sites bind 13 times more F. VIII than the low affinity sites. Ristocetin increased the binding of F. VIII to both types of binding sites by increasing the affinity of F. VIII for the platelet and increasing the total number of platelet binding sites. Chymotrypsin‐treated platelets were not aggregated by ristocetin and F. VIII: these platelets have less of the major platelet membrane glycoproteins and bind much less [125I]F. VIII than do buffer‐treated platelets with and without ristocetin.
The Reticulin Content of Bone Marrow in Acute Leukaemia in Adults
Authors: Manoharan A. , Horsley R. , Pitney W. R.
Published: March 2008

Summary. Marrow reticulin was studied by trephine biopsy in 44 patients with adult acute leukaemia at presentation and subsequently during the course of their illness. The findings indicate that: (1) an increase in marrow reticulin is common at presentation in patients with both acute lymphoblastic and acute non‐lymphoblastic leukaemia; (2) effective anti‐leukaemic therapy results in resolution of some or all of the increased marrow reticulin and is not contraindicated, even in patients with a marked increase in marrow reticulin; and (3) reappearance of an increase in marrow reticulin may be a sign of relapse of the leukaemia.
Abnormal Mitochondrial DNA in Acute Leukaemia and Lymphoma
Authors: Firkin Frank C. , Clark‐Walker G. D.
Published: March 2008

Summary. Electron microscopic examination was carried out on mitochondrial DNA molecules isolated from leucocytes in seven cases of acute leukaemia or leukaemic‐phase poorly‐differentiated lymphocytic lymphoma. There was a marked shift from the predominant circular monomeric form in normal leucocytes to circles with twice the normal circumference, as well as multiple interlocking circles in two of the four cases of untreated acute leukaemia, and in one of untreated lymphoma. This abnormal pattern of mitochondrial DNA evidently reflects an intrinsic aberration in the processing of mitochondrial DNA in some leukaemias and lymphomas, as it occurred in the absence of prior therapy with alkylating agents known to interact with DNA. Up to 47% of total mitochondrial DNA was present in such complex forms, which on steric grounds should be unsuitable as a template for replication of free monomers and possibly for messenger RNA production. The latter may be pertinent to previously reported abnormalities in acute leukaemia leucocytes which could be related to abnormal production of gene products of mitochondrial DNA.
Ferritin, a Sensitizing Substance in the Leucocyte Migration Inhibition Test in Patients with Malignant Lymphoma
Authors: Hancock B. W. , Bruce Lesley , May K. , Richmond J.
Published: March 2008

Summary. The nature of the factor in Hodgkin's disease involved spleen to which many patients with malignant lymphoma react in the leucocyte migration inhibition test has been investigated. Our results suggest that ferritin from Hodgkin's disease involved spleens is antigenically different to that prepared from normal spleen. Isoelectric focusing shows the presence of more acidic ‘isoferritins’in ferritin prepared from Hodgkin's disease involved spleen than in that prepared from normal spleen. Further observations using the leucocyte migration inhibition test suggest that sensitization to the abnormal ferritin, acting as an onco‐fetal tumour associated substance, may be responsible for the reaction of patients with malignant lymphoma in this test.
A Method for the Investigation of Reticuloendothelial Iron Kinetics in Man
Authors: Bentley D. P. , Cavill I. , Ricketts C. , Peake S.
Published: March 2008

Summary. A colloidal suspension of hydrolysed radio‐iron of high specific activity has been developed for the investigation of reticuloendothelial (RE) iron kinetics in man. Following intravenous injection this material is cleared rapidly by the RE system and the iron released into the plasma where it is bound to transferrin. There is no significant addition to the endogenous RE iron load, and it has proved possible to measure RE iron release without disturbing the normal iron flow.
Effect of Fibrin Degradation Products and Thrombin on Fibrinogen Synthesis
Authors: Ittyerah T. Roy , Weidner Noel , Wochner R. Dean , Sherman Laurence A.
Published: March 2008

Summary. The effect of intravenous administration of homologous fibrin degradation products and thrombin on fibrinogen synthesis was assessed in rabbits. The relative fibrinogen synthesis rate was calculated as a ratio of the amount of radiolabelled lysine incorporated into fibrinogen to the amount incorporated into albumin during the same measurement period. An increase in this ratio above control would indicate a relatively specific stimulation of fibrinogen synthesis as compared with albumin, which is not an acute‐phase reactant. Injection of 45 mg of ‘early’or ‘late’fibrin degradation products failed to produce a significant increase in the relative fibrinogen synthesis rate, suggesting that fibrin degradation products play no feedback role in controlling fibrinogen synthesis. Infusion of small amounts of homologous thrombin (15–25 NIH u) was followed by a small but statistically significant elevation of the relative fibrinogen synthesis rate. This was not accompanied by any increase in the levels of fibrinogen degradation products in plasma, or by any decrease in plasma fibrinogen concentration, possibly suggesting that thrombin can stimulate fibrinogen synthesis by a mechanism independent of significant fibrinogenolysis or intravascular coagulation.
Comparison of in Vitro Effects of Normal IgG and of a Monoclonal IgG on the Rheological Behaviour of Erythrocytes
Authors: Rovel A. , Vigneron C. , Streiff F.
Published: March 2008

Summary. Erythrocyte sedimentation, viscosity, electrophroetic mobility, and osmotic fragility were measured in a study of the rheological behaviour of the erythrocyte in vitro. In comparison with physiological saline solution, a suspending medium containing a γ2γ2 monoclonal IgG from a patient with multiple myeloma caused rheological changes 2–3 times as great as a medium with normal IgG.

Our results demonstrate the existence of nonimmunological interactions between erythrocytes and normal or monocolonal immunoglobulins, and they raise questions about the widely held assumption that paraproteins are structurally ‘normal’.
N‐Alkaline Phosphatase: a Potential Disease Marker for Lymphoproliferative Disorders
Authors: Neumann H. , Klein E. , Russell R. M. , Epstein S.
Published: March 2008

Summary. A characteristic alkaline phosphatase (orthophosphoric monoester hydrolase, alkaline pH optimum, EC 3.1.3.1) was detected in the sera of most patients with infectious mononucleosis, acute and chronic lymphatic leukaemia, non‐Hodgkin's lymphoma, Burkitt's lymphoma and nasopharyngeal carcinoma. The enzyme was also present in the sera of nine out of 26 patients with cancer of the cervix. N‐APase in these cases counted 30–100% of the total alkaline phosphatase activity. N‐APase was absent from the sera of healthy individuals and of patients with acute and chronic granulocytic leukaemia, breast cancer, colon cancer, rheumatoid arthritis, ulcerative colitis, systemic lupus erythematosis, hepatitis and obstructive jaundice. Only three of 22 patients with Hodgkin's disease showed N‐APase activity in the serum. In infectious mononucleosis the presence of N‐APase activity was well correlated with the clinical course. In 13 cases studied, the clinical improvement was associated with the decrease or disappearance of N‐APase activity. N‐APase activity could not be detected in white cells of acute myeloid leukaemic patients, nor in the cells of myeloid blastic crisis of chronic granulocytic leukaemia. It was present in the cells of lymphoid blastic crisis of chronic granulocytic leukaemia.
Cellular Mechanisms in the Regulation of Iron Absorption by the Human Intestine: Studies in Patients with Iron Deficiency before and after Treatment*
Authors: Cox T. M. , Peters T. J.
Published: March 2008

Summary.

An in vitro method for measuring initial rates of iron uptake by mucosal biopsies of human duodenum was used to study control mechanisms for iron absorption. Within the physiological range of intraluminal concentrations (18–450 μmo1/1) iron influx has many features of active, carrier‐mediated transport. In biopsies from six patients with iron deficiency anaemia, uptake rates were increased 2–3–fold at the higher concentrations, when compared with normal controls (P < 0.01) and overall were related inversely to serum transferrin saturation. Uptake was examined in four anaemic patients before and after therapy: the enhanced uptake fell to normal after repletion with iron, but was not reduced in two patients treated initially by red cell transfusion alone. Total mucosal iron in the anaemic patients was significantly lower at 58±7 nmol/mg protein, compared with 129±25 nmol/mg in normal subjects (P < 0.05). In the serial studies, iron therapy for 6 weeks corrected the anaemia but did not restore mucosal iron levels to normal, even though uptake had fallen to control values. The experiments indicate that iron deficiency reversibly induces brush border iron carriers, and suggest that in man initial entry into the enterocyte rather than cellular retention of iron is a major regulatory step in the control of iron absorption.
Positive Interaction between Agonists in the Aggregation Response of Human Blood Platelets: Interaction between ADP, Adrenaline and Vasopressin
Authors: Grant J. A. , Scrutton M. C.
Published: March 2008

Summary.

ADP, adrenaline and vasopressin interact positively as agonists in aggregating human blood platelets in vitro. This interaction is maximal if the addition of two of the agonists is separated by 10–20 s but decreases rapidly at longer intervals especially at low agonist concentrations. The agonist concentrations at which positive interaction gives full aggregation are significantly less than those required for such a response to each agonist alone. The lowest concentrations at which adrenaline and vasopressin interact positively are at least two orders of magnitude greater than the normal blood concentrations of these hormones, and at least an order of magnitude greater than the concentrations achieved in pathological states. Specifically antagonizing the adrenaline and ADP receptors showed that the response was to the second agonist added to the system. An inhibitor of intracellular Ca2+ movement (tetracaine) is equally effective in blocking the responses generated by a single agonist or by interaction of two agonists. Inhibitors which increase cyclic‐3′,5′‐AMP concentration (adenosine, prostaglandin E1, dipyridamole) are more effective against the response to a single agonist than that to agonist interaction. These data suggest that positive agonist interaction results from effects on the concentrations of second messengers within the platelet rather than from a direct interaction on the membrane receptors or the transmembrane coupling mechanisms.
A Specific, Fluorescent Activity Staining Procedure Applied to Plasma and Red Blood Cells in Congenital Factor XIII Deficiency
Authors: Henriksson P. , Stenberg P. , Nilsson I. M. , Rasovic N. , Kezic J. , Stenbjerg S.
Published: March 2008

Summary.

The activity staining procedure introduced by Stenberg & Stenflo (1979) has been applied to studies on human blood transamidases (transglutaminases; endo‐γ‐glutamine:ɛ‐lysine transferases; e.g. factor XIII). The technique combines agarose gel electrophoresis with activity staining based on the transamidase catalysed incorporation of monodansylthiacadaverine (N‐(5–amino‐3–thiapentyl)‐5–dimeth‐ylamino‐1–naphtalenesulfonamide) into casein. The method permits detection of plasma factor XIII activity down to 1% of the normal adult standard. The technique was used on plasma from two patients with tentative congenital plasma factor XIII deficiency (based on clot solubility). No activity was found in platelet poor as well as in platelet rich plasma which confirmed the diagnosis. In the erythrocytes studied in one of the two patients, transamidase activity was present which means separate genetic determinations of the plasma and red blood cell transamidases. Using immunoelectrophoresis, the plasma factor XIII b subunit was found to be 43% and 44% of the concentration in normal standard plasma.
The Effects of Surgical Trauma on Human Granulopoiesis
Authors: Philip Mark A. , Standen Graham , Fletcher John
Published: March 2008

Summary.

Marked changes in the concentration and proliferative state of circulating granulocytic progenitor cells (colony forming units in culture; CFUc) were observed in female patients following surgical trauma. Within one day of an abdominal hysterectomy there was an abrupt fall in the number of blood CFUc to between 10% and 20% of normal and an increase in the proportion synthesizing DNA which coincided with the maximum neutrophilia. Subsequently, as the neutrophil count declined, the CFUc concentration increased to supranormal values and the proliferative response persisted, both parameters returning to normal 2 weeks after surgery. These results suggest that, following surgical trauma, the increased demand for neutrophils is rapidly met by increased CFUc proliferation.
Glutamic Pyruvate Transaminase Phenotypes in Polycythaemia Rubra Vera
Authors: Kirkland D. J. , Welch S. G. , Povey Susan , Najfeld Vesna , Price D. J. , Lawler Sylvia D.
Published: March 2008

Summary

. Glutamate pyruvate transaminase (GPT) has been studied in the red cells of 46 patients with a confirmed diagnosis of polycythaemia rubra vera (PRV). The red cells of many of the patients showed low levels of enzyme activity. This activity could be restored by in vitro incubation with pyridoxal phosphate suggesting that the effect was due to low levels of B6 rather than to a primary abnormality of the GPT. Patients with the lowest levels of GPT activity were likely to have clonal chromosomal abnormalities in the bone marrow cells, particularly 20q —. Among 43 patients in whom the GPT phenotypes could be determined by an electrophoretic method there was a marked deficiency of heterozygotes. This disturbance in phenotypic expression may be related to the clonal nature of the disease in PRV, the clone showing lack of response to homeostatic controls and irregularities of gene expression.
Unequal α and β Globin mRNA in Reticulocytes of Normal and Mutant f/f Fetal Mice
Authors: Chui David H. K. , And Margaret Patterson , Bayley Stanley T.
Published: March 2008

Summary. Messenger RNA (mRNA) was isolated from adult as well as normal and mutant f/f fetal mouse reticulocytes by poly‐U affinity chromatography. mRNA from normal adult reticulocytes directed equal synthesis of α and β globin chains in wheat germ cell free translational system. mRNA from either normal or mutant f/f fetal reticulocytes directed 40% more α globin synthesis than β globin synthesis. These observations are suggestive that there is significantly more α mRNA than β mRNA in normal and mutant f/f fetal mouse reticulocytes.
Transient Increase of Fetal Haemoglobin in Kala‐azar
Authors: Schilirò G. , Musumeci S. , Russo A. , Marino S. , Sciotto A. , Russo G.
Published: March 2008

Summary.

Haemoglobin F (HbF) levels were significantly increawd in 40 children with kala‐azar in comparison with controls (3.36 ± 2.32 versus 0.90±1.8; P<0.01). The HbF was heterogeneously distributed among the red blood cells. The glycine residue of peptides γ CN3 were within the normal umbilical cord blood range, and the haemoglobin synthesis in vitro was balanccd. After recovery from kala‐azar the HbF fell within the normal range. These results suggest that increased production of HbF is associated with accelerated erythropoiesis due to temporary marrow stress.
Inhibitory Effect of Autologous Plasma on the Uptake of Tritiated Thymidine by Leukaemic Lymphoblasts and its Relation to Prognosis
Authors: Sugden P. J. , Lilleyman J. S.
Published: March 2008

Summary.

In vitro incorporation of tritiated thymidine was measured in blast cells from 33 unselected and untreated patients with lymphoblastic leukaemia (ALL) both when autologous plasma was present and also when it was substituted by pooled normal plasma. A similar procedure was carried out on 19 patients with acute non‐lymphoblastic leukaemia (AnonLL).

Plasma from the patients with ALL was variably found to reduce the uptake of the radiolabelled DNA‐precursor by their own blasts, with the most marked effect apparent in those with shorter survival times (P < 0.42). This phenomenon was not observed in AnonLL. The amount of plasma‐mediated inhibition shown by the ALL patients also correlated overall with their WBC, a known feature of a poor outlook, but even in the 21 patients with WBC below 20.0 ± 109/1 there was still a significant association between plasma effect and survival (P < 0.01).

The demonstration of such inhibitory plasma may be a useful prognostic marker in otherwise ‘standard risk’ ALL, and also may indicate a large tuniour inass where this is not reflected by the height of the circulating WBC.
In Vitro Effect of Cyclophosphamide Metabolites on Chromosomes of Fanconi Anaemia Patients
Authors: Berger R. , Bernheim A. , Gluckman E. , Gisselbrecht C.
Published: March 2008

Summary The effect of cyclophosphamide metabolites was studied on chromosomes of Fanconi anaemia patients, parents and controls. A high susceptibility of FA patients chromosomes was observed when low concentrations of sera of a cyclophosphamide‐treated patient was added to PHA‐stimulated lymphocyte cultures. No effect was observed with comparable concentrations on cells from FA patients or controls. The high susceptibility of FA cells is discussed in relation to the high sensitivity of FA patients to cyclophosphamide when used as a conditioning drug for bone marrow graft.
Inclusions in Red Blood Cells Containing Hb S or Hb C
Authors: Kim Haewon C. , Friedman Shlomo , Asakura Toshio , Schwartz Elias
Published: March 2008

Summary. To demonstrate and characterize red cell inclusions in 101 persons with Hb S or Hb C disorders three methods were used: (1) examination of unstained blood smears by dark field microscopy (DFM), (2) examination of blood smears after acid elution and staining (AE), and (3) measurement of membrane‐associated denatured haemoglobin (MADH) in ghosts. The control group had inclusions in less than 5% of red cells by DFM and AE and the mean percentage of MADH per total cellular Hb was 0.030±0.016%. The highest percentages of red cells with inclusions and of MADH were present in clinically severe haemoglobin disorders, e.g. homozygous sickle cell disease (Hb SS) with less than 10% Hb F and Hb SOArab, with successively lower percentages in moderate to severe disorders, e.g. Hb SS‐α thalassaemia, Hb S‐β0 thalassaemia, Hb SC disease, and Hb SS with more than 10% Hb F, indicating agreement in results by three methods. In asymptomatic or mild disorders, e.g. Hb S‐β+ thalassaemia, Hb CC, Hb AC and Hb AS, the results by AE and measurements of MADH were the same or similar to those in controls, while those by DFM were different. Of 56 patients with Hb SS or Hb SC, the group with functional asplenia had higher percentages of MADH and of red cells with inclusions than those with functioning spleens. Our study suggests that inclusions in sickling disorders may be due to denatured Hb S, with AE being the more accurate method for visualizing these inclusions, as results by this method correlate better with the amount of MADH than those by DFM.
Interaction between the Glucose‐6‐Phosphate Dehydrogenase Deficiency and Thalassaemia Genes at Phenotype Level
Authors: Sanna G. , Frau F. , Melis M. A. , Galanello R. , Virgiliis S. De , Cao A.
Published: March 2008

Summary. No significant differences were observed in the mean values of Hb A2 levels and red cell indices between G6PD‐ and G6PD+β thalassaemia carriers apart from the MCV, which was significantly higher in β thalassaemia G6PD‐ subjects, but still in the thalassaemia carrier range. No difference was seen between G6PD+ and G6PD‐α thalassaemia carriers. G6PD+β thalassaemia carriers show a significant increase in G6PD levels expressed as activity per g of Hb and to lesser extent as activity per number of red cells x 109; in G6PD+α thalassaemia carriers this increase is statistically significant only when the enzyme levels are expressed as activity per g of Hb. G6PD‐β thalassaemia carriers had enzyme levels higher than non‐thalassaemic G6PD‐ subjects only when the activity is expressed per g of Hb. G6PD activity was found to be increased in G6PD+ and G6PD‐ Hb H disease patients.
Investigations into the in Vitro Sensitivity to Erythropoietin of Haematopoietic Tissue from Ex‐hypoxic, Erythrocytotic Mice
Authors: Dunn C. D. R.
Published: March 2008

Summary. If ‘sensitivity’ is defined as the ratio of haem synthesis in erythropoietin (Ep)‐stimulated cultures to that in cultures without added Ep, then haematopoietic tissue of ex‐hypoxic mice is less sensitive to Ep in vitro than similar tissue from normal donors. This appears to be due primarily to the loss of erythropoietin responsive cells from the marrow and spleen. In addition, saline extracts of mature erythrocytes inhibited erythropoiesis in normal bone marrow cultures in a manner directly related to the ‘haematocrits’ used during their preparation. These data support recent suggestions that the preference of erythrocytotic mice over normal animals for Ep assay probably can be attributed to their low baseline level of erythropoiesis rather than an increased sensitivity to Ep.
Isolation of Fibrinogen–Fibrin Related Antigen from Human Plasma by Immunoaffinity Chromatography: its Characterization in Normal Subjects and in Defibrinating Patients with Abruptio Placentae and Disseminated Cancer
Authors: Merskey C. , Johnson A.J. , Harris J. U. , Wang M. T. , Swain S.
Published: March 2008

Summary. Highly purified, fibrinogen–fibrin related antigen (FR‐antigen) was isolated with good recovery from 1.0–2.0 ml of human plasma, by immunoaffinity chromatography with antibody specific for fibrinogen and fibrin, and plasmin degradation products X, Y, D and D‐D dimer. In FR‐antigen from defibrinating patients there was evidence for thrombin activity alone (mainly disseminated cancer) or both plasmin and thrombin (mainly abruptio placentae). Thus, the molar ratio of N‐terminal Gly – Tyr in the FR‐antigen of 18 of 20 patients strongly suggested thrombin activity (95th percentile). In addition, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS‐PAGE) on unreduced samples frequently showed bands similar in mol wt to fragments X, Y and D, and in the reduced samples A α and Bβ chain degradation, both indicating plasmin activity. N‐terminal β chain Ala was elevated in the antigen of four of 20 patients, also suggesting plasmin activity (99th percentile). Combined thrombin, plasmin and factor‐XIII activity, as shown by bands in similar position to D‐D and γ chain dimers, was commonly associated with high levels of serum FR‐antigen (> 10 mg/dl). In some defibrinating patients, especially those with disseminated cancer, heterogeneity of unreduced FR‐antigen and Aα chain degradation, both indicators of mild plasmin‐like activity which are commonly seen in normals, were absent.
Red Cell Glutathione Deficiency: Clinical and Biochemical Investigations using Sheep as an Experimental Model System
Authors: Tucker E. M. , Young J. D. , Crowley C.
Published: March 2008

Summary. The biochemical properties of red cells from normal sheep and sheep with three types of red cell glutathione (GSH)‐deficiency were compared. One deficiency was due to an impaired transport system for amino acids (lesion 1), one was the result of a diminished activity of γ‐glutamyl cysteine synthetase (GC‐S) (lesion 2) and the third was a combined deficiency produced by selective breeding to give animals with both lesions 1 and 2. Under normal husbandry conditions no clinical symptoms were apparent in sheep with lesion 2, but red cells from sheep with lesion 1 and lesions 1+2 showed an increased osmotic fragility, a greater tendency to form Heinz bodies and a shorter potential life span than normal. These deficiencies were not found in tissues other than blood. Normal and GSH‐deficient red cells had the expected low concentrations of 5‐oxoproline.

The effects of the toxic agents phenylhydrazine, s‐methylcysteine sulphoxide and nitrite in vivo were measured in sheep of the different types. GSH‐deficient sheep responded earlier and more dramatically than normal sheep, showing greater methaemoglobin formation, and for phenylhydrazine and s‐methylcysteine sulphoxide, more severe anaemia. Sheep with the combined lesions were in general the most susceptible, but even they had the ability to recover from moderately severe oxidative challenge.
Reduced Generation of Procoagulant Activity by Endotoxin‐stimulated Mononuclear Cells from Patients with Chronic Myeloid Leukaemia
Authors: Cortellazzo S. , Viero P. , Barbui T. , Colucci M. , Semeraro N.
Published: March 2008

Summary. The capacity of blood mononuclear cells to produce procoagulant activity upon stimulation with bacterial endotoxin in vitro was studied in 21 untreated patients with chronic myeloid leukaemia (CML). Procoagulant activity developed by patients’ cells after prolonged incubation with endotoxin was significantly lower than that produced by cells from a matched control group (P< 0·001). Reduced activity was seen in all patients when each of them was compared to a matched control studied simultaneously. It was below 50% of the control in 19 patients, and in eight of these it was less than 10%. These findings suggest that qualitative abnormalities in mononuclear cell function may exist in CML and might explain why these patients are less prone to thrombotic complications than those with other myeloproliferative diseases.