bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Treatment of Iron Deficiency Anaemia by Iron‐Dextran Infusion: A Radio‐Isotope Study
Authors: Will G. , Groden B. M. 
Published: March 2008

Summary A 59Fe labelled preparation has been used to follow the distribution and fate of intravenously administered iron‐dextran (Imferon) in 10 patients with iron deficiency anaemia and three non‐anaemic adult female subjects.In all anaemic patients a satisfactory reticulocyte response occurred with a peak between the 8th and 10th day, and was followed by a progressive and maintained rise in haemoglobin. The mean weekly haemoglobin increments for the first 3 weeks were 1.9, 1.6 and 0.7 g. and the haemoglobin had reached normal levels in all by the 9th week.Surface scintillation counting showed increasing radioactivity over liver, spleen and sacrum up to the end of the 1st week, followed by a gradual decrease during the next 2 weeks so that by the 21st day the radioactivity over these sites had fallen to below the initial values. The sternal counts dropped during the 1st week, then levelled off and thereafter showed a slow but maintained increase. The findings in the normal subjects did not differ significantly from those in the anaemic patients.There were no general systemic reactions during or after the infusions, nor was there evidence of disturbance of renal or hepatic function. Local venous thrombosis occurred in two patients.Iron‐dextran is well tolerated when given intravenously. The stability of the compound is shown by the absence of untoward symptoms in the immediate post‐infusion period when plasma iron levels are very high. The haematological response is rapid and complete, and the results compare favourably with those obtained by other methods of iron therapy.
Spontaneous Inhibitors of Factor VIII
Authors: Green David 
Published: March 2008

Factor‐VIII inhibitors accompanying severe allergic reactions to penicillin have now been described in six patients. The inhibitor in the present case was identified as an IgG‐globulin, and seemed to originate from the altered immunologic state induced by the allergic reaction, rather than being specifically related to penicillin or penicillin antibody. During the performance of these experiments it was observed that unusually strong solutions of penicillin were capable of removing antibody globulin from plasma. After incubation with penicillin, the Factor‐VIII inhibitors of non‐haemophilic origin (designated ‘spontaneous’inhibitors) appeared to retain greater activity than did those of haemophiliacs. The reason for this greater activity was made clear by an examination of the kinetics of the reaction between spontaneous inhibitors and Factor VIII. Spontaneous inhibitors were capable of inactivating amounts of Factor VIII out of proportion to their degree of dilution. They also inactivated the Factor VIII more rapidly than did haemophilic inhibitors, but permitted more residual Factor‐VIII activity. This residual activity was reduced more than expected by subsequent incubation with haemophilic inhibitors, and less than expected with spontaneous inhibitors. It was suggested that one molecule of a spontaneous inhibitor was capable of complexing more than one molecule of Factor VIII, but that the Factor‐VIII molecules in the complex retained some degree of Factor‐VIII activity. This activity could be removed by subsequent incubation with haemophilic inhibitors but not with spontaneous ones.Identification of the type of inhibitor was important from a therapeutic standpoint. While repeated additions of Factor VIII to the plasma of patients with inhibitors of haemophilic origin resulted in increasing levels of Factor VIII, such was not the case with spontaneous inhibitors. If the initial addition of Factor VIII failed to provide a therapeutic level, repeated additions were not likely to do so. Although the kinetics of the reaction between spontaneous inhibitors and porcine AHG were similar to those described with human Factor VIII, the inhibitors were always less active against the animal preparation. Treatment with d‐penicillamine, high concentrations of penicillin, immunosuppressive agents, and corticosteroids proved to be of limited value in patients with spontaneous inhibitors. It was concluded that a vigorous attack on the coexistent disorder responsible for stimulating the production of the inhibitor offered the best prognosis for the patient.
Study of Nine Families with Haemoglobin‐Lepore
Authors: Duma H. , Efremov G. , Sadikario A. , Teodosijev D. , Mladenovski B. , Vlaški R. , Andreeva M. 
Published: March 2008

The results of the clinical and haematological investigation of the members of nine families having a minor haemoglobin variant, designated Hb‐Lepore, are presented. The abnormal haemoglobin has been found in the homozygous state (three cases) in combination with A2 thalassaemia (four cases) and in the heterozygous state (56 cases).In one homozygous individual very high concentrations of HbF and complete absence of HbA and HbA2 were observed; Hb‐Lepore was found in small quantity (8.6 per cent). The haemoglobin studies of the second homozygous individual were performed shortly after transfusion; they showed the presence of HbA and HbA2. The third homozygote was not available for haemoglobin studies.In the four double heterozygous individuals a high quantity of HbF and small amounts of the abnormal haemoglobin were found. In two of them the haemoglobin studies were performed 5 and 10 months after the last transfusion and the HbA and HbA2 were present in the quantity of 36 and 29 per cent, and 0.9 and 1.4 per cent, respectively.The clinical and haematological picture in both the homozygous and double heterozygous individuals were indistinguishable from thalassaemia major, but they were more severe in the three homozygous individuals than in three of the four double heterozygous patients. In the fourth heterozygous patient the severity was similar to that seen in the homozygous state. The heterozygous carriers showed the presence of low amounts of Hb‐Lepore and HbF with an altered erythrocyte morphology resembling thalassaemia trait. The HbA2 concentration was somewhat lower than normal (mean value, 1.86 per cent).
Proliferative Activity of Leukaemic Cells at Various Stages of Acute Leukaemia of Childhood
Authors: Foadi Minou D. , Cooper E. H. , Hardisty R. M. 
Published: March 2008

The DNA synthesis and content of individual leukaemic cells have been measured respectively by in‐vitro labelling with tritiated thymidine and micro‐densitometry of Feulgen‐stained cells. These investigations have been carried out on bone‐marrow and blood samples obtained from children at the time of diagnosis of acute leukaemia, and during subsequent remissions and relapses.At diagnosis, the labelling index of bone‐marrow blasts was low (6.8 ± 3.51 per cent), and that of blasts in the peripheral blood was usually still lower; most cells were at the 2n mode. There was no correlation between the labelling index and either the numbers of blasts in bone marrow or blood, or the duration of symptoms. During induction of remission, labelled cells disappeared more rapidly from the blood than unlabelled cells.In relapse, the labelling index was significantly higher than at diagnosis, and there was evidence of aneuploidy in most patients, as shown by the distribution of DNA content. The mean labelling index of the small proportion of blasts in the marrow of five patients during remissions was intermediate between those found at diagnosis and during relapse.The labelling index of leukaemic cells with tritiated uridine was high both at diagnosis and during relapse, the most heavily labelled cells usually being amongst the largest members of the population.The possible significance of these findings is discussed in relation to the natural history of the disease.
Metabolic Responses of Separated Leucocytes to Phytohaemagglutinin: Effects of Anaerobiasis, Actinomycin D and Puromycin
Authors: Rabinowitz Yale , Schimo Inge , Wilhite Betty A. 
Published: March 2008

Metabolic changes needed for response to PHA were sought. Normal lymphocytes (N‐L), which respond strongly to PHA showed in 1.5–2.5 hour cultures sharp increases in RNA and protein synthesis, in glycolysis and O2 consumption. Leukaemic lymphocytes (CLL‐L), which respond poorly to PHA, had higher initial rates of synthesis of RNA and protein, but lesser glycolytic activity than N‐L. Moderate increase in glycolysis occurred with PHA. Polymorphonuclear leucocytes (PMN), which do not transform with PHA, showed increased RNA synthesis and glycolysis in brief cultures, but protein synthesis decreased. N‐L and PMN showed a moderate increase in glycolysis in N2, while CLL‐L responded very strongly. Actinomycin D blocked RNA synthesis and puromycin blocked protein synthesis, but neither prevented initial stimulation of glycolysis by PHA. Glycolysis decreased, however, and blast‐cell formation was prevented in longer cultures with either antibiotic. Protein and RNA synthesis apparently are required to maintain the increased levels of glycolysis needed for cell transformation.It is suggested that PHA acts at allosteric sites on protein repressors or inducers of operator genes to activate a series of reactions which simulate those in immunological responses.
A Study of ‘Haemosiderin’in the Marrow of the Femur of Normal Young Adult Rabbits Compared with that in Rabbits 4 Months after an Intravenous Injection of 239Pu(NO3)4
Authors: Beno Milan 
Published: March 2008

A study of the distribution of cells containing iron, as demonstrated by Perls’reagent, in the marrow of the femur of normal young adult rabbits in comparison with that in rabbits of the same age group 4 months after an intravenous injection of 239Pu(NO3)4 is described.The number of iron containing cells, which are probably macrophages, was found to be variable in the length of the bone and also from one normal rabbit to another. The amount of pigment in any one cell was also variable.A significant increase in the number of iron containing cells and in the amount of pigment the cells contained was noted in the marrow of the femur of rabbits 4 months after a single intravenous injection of 239Pu(NO3)4, compared with the normal controls. 239Pu aggregates close to the mineralized surface were not characteristically associated with haemosiderin.This work was carried out at the Medical Research Council Unit for Research on Bone‐Seeking Isotopes, Oxford, while the author was holding a World Health Organization Fellowship.I am indebted to Dr. Janet Vaughan and Mrs. Betty Bleaney for much helpful advice and discussion. I also wish to thank Dr. David Taylor, Department of Biophysics, The Royal Cancer Hospital, for injecting the rabbits with 239Pu(NO3)4. I appreciate the technical help of Mr. John Halfacre.
Surface Ultrastructure of Human Leucocytes, Mouse Macrophages and Rat Liver Cells, and of Isolated Nuclei and Nucleoli
Authors: Clarke J. A. , Salsbury A. J. , Rowland G. F. 
Published: March 2008

Summary. Examination of preparations from the human, rat and mouse with special reference to white blood cells, using the Cambridge Stereoscan Electron Microscope, showed that there is almost certainly a characteristic surface appearance of cells, nuclei and nucleoli from various tissues.The most important findings were:

The experiments concerning non‐specific stimulation of mouse peritoneal macrophages showed that this technique was suited to demonstration of subtle dynamic changes in the cell surface membrane. The technique has already been employed in a similar respect with regard to the red cell.
It was possible for the first time to look at the inner aspect of nuclear membrane at ultrastructural levels in three dimensions. While it would be difficult to draw conclusions from nuclear membranes disrupted by electron bombardment, examination of the lymphocyte nuclear membrane resulting from ultrasonic disintegration showed that the external surface appearances had been preserved and were similar to those of intact lymphocyte nuclei.
Comparison of white cell nuclei and nucleoli with rat liver nuclei and nucleoli revealed marked differences. The surface irregularity of the liver nuclei was never seen in white cell nuclei and the liver nucleoli were of individual character. An opportunity is presented for comparing the surface changes in these structures during the numerous experimental procedures carried out on rat liver and equating these with cellular function.
The granular white cells and their precursors were disappointing in their surface characteristics and it was impossible to identify the individual members of the series. In contrast the surface identity of the lymphocyte is of importance, since a method is now available for exhibiting the membrane changes which are known to occur from immunological causes. Work is currently being carried out to detect and evaluate such changes.
The Correlation between Red‐Cell Survival and Excess of α‐Globin Synthesis in β‐Thalassaemia
Authors: Vigi V. , Volpato S. , Gaburro D. , Conconi F. , Bargellesi A. , Pontremoli S. 
Published: March 2008

Summary:In 13 subjects affected by β‐thalassaemia major, in three subjects affected by β‐thalassaemia minor and in five normal healthy persons haemoglobin synthesis and the survival of red cells transfused into normal, group compatible, healthy recipients has been studied. The existence of an excess of newly synthesized α‐chains and of a negative correlation between the excess α‐chain and the red‐cell survival has been demonstrated. The harmful role of the α‐chain excess on the erythrocyte and the implications of this finding are discussed.
Nodal and Extranodal Malignant Lymphoma in Israel: An Epidemiological Study
Authors: Modan Baruch , Shani Mordechai , Goldman Boleslav , Modan Michaela 
Published: March 2008

Summary:Records of all patients with malignant lymphoma diagnosed in Israel between 1960 and 1964 were reviewed. Evidence for different patterns of the disease in various age and population groups has been noted. Thus, in the younger age groups and in the Asian‐African segment of the population, as well as the Arabs, the disease presented more often at extranodal sites, while in older age groups and among the Europeans it was predominantly in lymph nodes or generalized at presentation.The alimentary forms were more prevalent at younger ages, and in African‐born patients and Arabs. Within the alimentary forms the small intestine was the major site in the younger age groups and the stomach in the older age groups.The different patterns of the disease suggest differential susceptibility of both subject and tissue to possible environmental carcinogens or inducing agents.In the course of a recent country‐wide study of malignant lymphomata in Israel, several differences in the site of presentation in different age groups and ethnic groups were noted. Such differences may be important both clinically and epidemiologically.
Sites of Platelet Destruction in Idiopathic Thrombocytopenic Purpura
Authors: Aster Richard H. , Keene Willis R. 
Published: March 2008

Summary:Platelet life span and sites of platelet sequestration were studied on 20 occasions in 15 patients with idiopathic thrombocytopenic purpura (ITP) using 51Cr‐labelled cells and external scintillation scanning. In 16 cases when platelet concentrations were greater than 5000 per cu.mm., labelled cells were destroyed predominantly in the spleen. Only in four patients with platelet levels less than 2500 per cu.mm. was significant hepatic sequestration observed. In the latter group, half‐disappearance times of labelled cells were extremely short, ranging from 2 to 9 minutes. The data suggest that in ITP, as in other clinical and experimental situations where circulating cells are sequestered following their reaction with antibodies, lightly sensitized cells are removed from the circulation at a relatively slow rate by the spleen, while more heavily sensitized cells are liable to rapid destruction in the liver. Thus, in ITP, the site in which labelled cells are sequestered appears related to the severity of the disease at the time of study, rather than to any qualitative difference in the nature of the disease among individual patients.
Polycythaemia Vera and Myelosclerosis: A Bone Marrow Study
Authors: Roberts B. E. , Miles D. W. , Woods C. G. 
Published: March 2008

Summary:Trephine bone biopsies have been performed on patients suffering from polycythaemia vera and other myeloproliferative disorders. These were assessed histologically with particular reference to cellularity and reticulin. It was found that marrow cellularity, when measured using Curtis's modification of a Chalkley array of points, is raised in polycythaemia vera and may become normal following radioactive phosphorus therapy.Marrow cellularity was also shown to be proportional to spleen size and a linear relationship between marrow cellularity and packed cell volume was demonstrated, providing major degrees of splenomegaly were excluded.Studies of the reticulin fibres in bone marrow showed that they increase in density with an increase in marrow cellularity, and that an increase is neither characteristic of any specific myeloproliferative disorder nor is it related to radioactive phosphorus therapy.It was concluded that the histological diagnosis of myelosclerosis should be confined to those bone marrows showing evidence of fibroblastic proliferation and disruption of marrow architecture by a process of fibrosis, and should not be made on the basis of reticulin density.
Red Cell Aldolase Deficiency in Hereditary Spherocytosis
Authors: Chapman Robert G. 
Published: March 2008

Summary:Red cell aldolase activity decreases normally with cell age at a mathematically predictable rate. Compared to aldolase activity so predicted for red cells of the same age, activity of this glycolytic enzyme was 35 per cent deficient (range 18–53 per cent) in 20 splenectomized patients from eight unrelated families with typical hereditary spherocytosis. In two unsplenectomized patients with hereditary spherocytosis red cell age was estimated from measurement of their diisopropyl‐fluorophosphate (DF32P)‐labelled red cell survivals, and deficiencies of 62 and 55 per cent in red cell aldolase activity observed. The rates of glycolysis in intact cells and haemolysates measured under conditions designed to produce maximum rates of lactate formation were 20–30 per cent less than expected for the red cell age in the splenectomized subjects. Since patients with hereditary spherocytosis are probably heterozygous for the genetic defect presumed to be present in this disease, the magnitude of deficiency was compared to those reported in heterozygotes for inherited red cell abnormalities such as sickle haemoglobinopathy, glucose‐6‐phosphate dehydrogenase deficiency and pyruvate kinase deficiency and it was found to be similar. This suggests that a deficiency in red cell aldolase activity may be the basic biochemical lesion in hereditary spherocytosis. One of the products of the aldolase reaction, dihydroxyacetone phosphate, is known to be an important precursor for phospholipid in other tissues, suggesting a possible relationship between red cell aldolase deficiency and the known red cell membrane abnormalities of hereditary spherocytosis.
Vitamin B12 Binding Proteins in Liver Disease
Authors: Retief F. P. , Vandenplas L. , Visser H. 
Published: March 2008

Summary:Vitamin B12 binding proteins were studied in patients with acute and chronic liver disease, and compared with vitamin B12 binders in chronic myeloid leukemia.In acute viral hepatitis marked elevation of serum vitamin B12 was common. Although the serum vitamin B12 rose as high as that found in chronic myeloid leukaemia the unsaturated vitamin B12 binding capacity (UBBC) was markedly elevated in the latter condition, whereas it was decreased in acute liver disease. In cirrhosis a moderate increase of serum vitamin B12 and UBBC was common.Urinary vitamin B12 excretion increased significantly only when the serum vitamin B12 became markedly elevated in hepatitis.As in chronic myeloid leukaemia the alpha‐globulin vitamin B12‐binder carried the bulk of the elevated serum vitamin B12 in acute liver disease; the beta‐globulin vitamin B12‐binder was decreased in serum but seemed to be the predominant binder in urine. This suggests that renal loss of beta‐globulin binder is greater than renal loss of alpha‐globulin binder. Only minor albumin binding of vitamin B12 in liver disease was found in spite of marked elevation of the serum vitamin B12 level. In cirrhosis the serum alpha‐globulin binder was often increased and beta‐globulin binder decreased. The cause and significance of these findings are discussed.The ability of serum vitamin B12‐binders of liver disease to ‘transfer’57Co‐B12 to tissue was investigated in an in vitro rat liver homogenate system. In a limited study, vitamin B12 uptake appeared to be within normal limits, except for suboptimal uptake from the beta‐globulin binder in cirrhotic serum. Poor vitamin B12 uptake from chronic myeloid leukaemia serum (in particular alpha‐globulin binder) was confirmed.
Shortening of the Cell‐Cycle Time of Erythroid Precursors in Response to Anaemia
Authors: Hanna I. R. A. , Tarbutt R. G. , Lamerton L. F. 
Published: March 2008

Summary:The method of labelled mitoses has been used to obtain estimates of the cell‐cycle time (and of its constituent phases) of erythroid precursors in normal adult rats, and in adult rats subjected to transient and protracted anaemias. It has been shown that considerable reductions occur in the cycle time in the anaemic rats, and that these reductions are due to decrease in the duration of both the S and G1 phases. The decreased cycle time is discussed in relation to the number of divisions that the erythroid precursors undergo during maturation.
The Effect of Bleeding on the Number of in Vitro Colony‐Forming Cells in the Bone Marrow
Authors: Metcalf Donald 
Published: March 2008

Summary:Bleeding 0.3 ml. daily for 3 days reduced the total number of in vitro colony‐forming cells in the bone marrow of C57Bl and BALB/c mice to less than 50 per cent of that in control mice, but caused a significant increase of erythropoietic cells in the bone marrow. Transfusion of packed red cells combined with bleeding prevented this fall in in vitro colony‐forming cells. Bled mice developed spleen enlargement with some increase in the total number of in vitro colony‐forming cells in the spleen but this did not compensate for the reduced number of such cells in the bone marrow. Splenectomy did not affect this response of in vitro colony‐forming cells in the bone marrow. Cortisone reduced the bone marrow content of in vitro colony‐forming cells. Serum levels of colony‐stimulating factor were not elevated in response to bleeding. The results suggest that in vitro colony‐forming cells are not erythropoietic cells but may share a common ancestor with erythropoietic cells.