bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Collagen on Platelet Glycolysis and Nucleotide Metabolism
Authors: Loder P. Bronwen , Hirsh J. , de Gruchy G. C.
Published: March 2008

Summary. Glycolytic activity and nucleotide metabolism were studied in normal resting platelets and platelets exposed to collagen. Lactate production was found to be a more sensitive index of glycolytic activity than glucose consumption. In the presence of added glucose, the rate of lactate production was linear for at least 60 minutes. In the absence of glucose, lactate production continued for 60 minutes and appeared to be independent of glucose for the first 10–15 minutes.

Addition of both collagen and pure tropocollagen to the platelet suspension produced a significant and constant increase in glycolytic rate. This was associated with release of ATP and ADP and a small but significant increase in total ATP. Addition of ADP in concentrations similar to those released by collagen had no effect on glycolytic activity. Addition of calcium ions produced release of nucleotides but no increase in glycolytic rate. EDTA inhibited glycolysis both in the resting platelets and in the presence of collagen.

It is suggested that the stimulation of glycolysis by collagen may be due to the action of collagen on one or more rate‐limiting glycolytic enzymes.
Deranged DNA Synthesis by Bone Marrow from Vitamin B12‐Deficient Humans*
Authors: Metz Jack , Kelly Alan , Swett Virginia Chapin , Waxman Samuel , Herbert Victor
Published: March 2008

Summary. The synthesis of thymine DNA from deoxyuridine and uridine was studied by culturing human bone marrow for 1–3 hours in the presence of radioactive‐labelled nucleosides. In the current study, this in vitro system appeared useful to test the potential efficacy of agents (such as methionine) which might be used to improve or retard improvement of patients with megaloblastic anaemia.

In the bone marrow from patients with B12‐deficient or folate‐deficient megaloblastic anaemia, there was defective incorporation of deoxyuridine into thymine DNA. This defect was partially corrected by added B12 in the B12‐deficient but not the folate‐deficient marrows, and completely corrected by folic acid (pteroylglutainic acid) in both types of deficient marrow. The folate antagonist rnethotrexate blocked the corrective effect of B12. Incorporation of labelled uridine into DNA of B12‐deficient megaloblastic marrow was enhanced less by B12 than by PGA. Vitamin B12 antagonists failed to depress the incorporation of labelled uridine into DNA in bone marrows from both normal and B12‐deficient patients.

These results support the concept that inadequate DNA synthesis in B12 deficiency is due in large measure to blockade in folate metabolism brought about by lack of B12. 5‐Methyl‐tetrahydrofolate, which may accumulate in B12 deficiency, failed to correct the defect in DNA synthesis, adding further evidence to the concept of metabolic trapping of this form of folate in B12 deficiency. Thus, riboside reduction in man may be independent of B12, as it is in E. coli, rather than dependent on B12, as it is in L. leichmannii.
Changes in Erythrocyte Membrane and Autohaemolysis during in Vitro Incubation
Authors: Langley G. R. , Axell M.
Published: March 2008

Summary. Spontaneous autohaemolysis occurs as sterile defibrinated blood is incubated at 37°C. This study was undertaken to identify the membrane changes which occurred during autohaemolysis and the effect upon these of supplementary glucose.

After 24 hours of incubation the earliest membrane change recognized was the loss of small amounts of cholesterol; this occurred equally in incubations with and without added glucose. Spherocytes were prominent in incubations without added glucose but were infrequent when supplementary glucose was provided. During the second 24 hours of incubation cholesterol loss increased and phospholipids eluted from the cell surface. In this period of incubation cholesterol and phospholipid loss was less in incubations provided with supplementary glucose. The major individual phosphatides lecithin, sphingomyelin, phosphatidylethanolamine and phosphatidylserine were lost in proportion to their original concentration in the membrane. Membrane protein did not decrease as cell lipid loss occurred.
Fibrinogen Catabolism in Microangiopathic Haemolytic Anaemia
Authors: Baker L. R. I. , Rubenberg M. L. , Dacie J. V. , Brain M. C.
Published: March 2008

Summary. Fibrinogen catabolism has been studied in six patients with microangiopathic haemolytic anaemia, three patients with fragmentary haemolytic anaemia following the insertion of valve prostheses into the heart and ten control patients. Increased rates of catabolism of 131 I‐fibrinogen were found in the patients with microangiopathic haemolytic anaemia. Evidence of enhanced fibrinolysis was not present.

This finding suggests that intravascular coagulation is a feature of some cases of microangiopathic haemolytic anaemia and supports the hypothesis that the interaction of red cells with fibrin may result in the characteristic morphological appearances in these cases.
Starch Gel Electrophoresis of Erythrocyte Membranes in Hereditary Spherocytosis
Authors: Zail S. S. , Joubert S. M.
Published: March 2008

Summary Solubilized red cell stromal proteins were obtained from normal donors and from six cases of hereditary spherocytosis. The proteins were subjected to starch gel electrophoresis at acid pH and incorporating urea and mercaptoethanol. No significant qualitative variations in the electrophoretic separations were observed. The significance of these findings is discussed.
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.
The Role of Intravascular Haemolysis and the Reticulo‐Endothelial System in the Production of a Hypercoagulable State
Authors: Rabiner S. Frederick , Friedman Lila H.
Published: March 2008

Summary Infusion of autologous haemolysed erythrocytes (haemolysate) into dogs produces hypercoagulability frequently followed by actual intravascular coagulation as evidenced by depressed Factor V and Factor VIII activity, fall in fibrinogen and demonstrable pulmonary artery thrombi. Depression of the reticulo‐endothelial system by carbon or splenectomy produces accentuation of this phenomena. It is postulated that haemolysis can be an important contributing factor in the pathogenesis of ‘the syndromes of disseminated intravascular coagulation’. It is also suggested that the thrombotic phenomena associated with the generalized Shwartzman phenomenon, thrombotic thrombocytopenic purpura, the haemolytic uraemic syndrome, paroxysmal nocturnal haemoglobinuria, and incompatible blood transfusion reaction, may be related to intravascular haemolysis.
RNA Metabolism in Normal and Leukaemic Leucocytes: Further Studies on RNA Synthesis
Authors: Silber Robert , Unger Kenneth W. , Ellman Louise
Published: March 2008

Summary The Synthesis of RNA* has been investigated in leucocytes isolated from the blood of normal subjects and patients with leukaemia. In addition to ribosomal and soluble RNA, white cells make a rapidly labelled RNA with properties of messenger RNA. RNA synthesis in leukaemic cells is sensitive to pancreatic ribonuclease and actinomycin D, thereby offering evidence in favour of DNA‐dependent RNA synthesis in these cells. Leucocytes from some patients with leukaemia manifest a two‐ to five‐fold increase in uridine incorporation into RNA when compared to normal cells. Inhibition of RNA synthesis in leucocytes by alkylating agents administered in vivo or in vitro was observed.
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.
Blood Volume Changes in Chronic Bronchitis and Emphysema
Authors: Hume R.
Published: March 2008

Red‐cell volume (RCV) and plasma volume (PV) measurements were made in 15 patients with chronic bronchitis and emphysema and related to the arterial oxygen tension (Po2) and the arterial carbon dioxide tension (Pco2) during the quiescent phase of the respiratory condition. It was found that the percentage increase in RCV was inversely related to the logarithm of the Po2 and that the change in RCV was similar to that of normal people living at various altitudes. The logarithm of Pco2 was directly related to the percentage increase in RCV and the Pco2 did not affect the erythropoietic response to hypoxia. The mean PV was significantly smaller than normal although increased in the two patients with heart failure. The relationship between the log Po2 and percentage change in PV did not reach significant levels. The implications of the findings are discussed.
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).
Electron‐Microscopical Study of Bone Marrow Cells in a Case of Chediak‐Higashi‐Steinbrinck Syndrome
Authors: Efrati Pinhas , Danon David
Published: March 2008

Phase‐contrast and electron‐microscope studies of bone marrow cells in a case of Chediak‐Higashi‐Steinbrinck syndrome are presented. Phase‐contrast microscopy shows giant granules in young granulocytes and in dividing cells. The electron‐microscopical findings are generally in agreement with similar studies by other authors. In addition, structures similar to leucocyte giant granules were observed in erythrocytes. The syndrome seems to be associated with a defective membrane stability of cytoplasmic granules and membrane‐bound lysosomes.
The Fine Structure of Platelet Fibrin
Authors: Cuddigan B. J. , Kay D.
Published: March 2008

Fibrinogen has been extracted from well‐washed platelets. On treatment with thrombin it forms fibrin which when negatively stained and examined in the electron microscope shows exactly the same complex band structure as that found in plasma fibrin. It is concluded that since the fibrins are indistinguishable, platelet and plasma fibrinogen are unlikely to be structurally different.
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.
The in vitro Effect of Phytohaemagglutinin on Separated Human Bone Marrow Cells
Authors: Pegrum G. D. , Ready Doreen , Thompson Elizabeth
Published: March 2008

Cells from 60 marrow aspirates were separated using columns of glass microspherules. The effect of PHA on the viability and synthesis of DNA and RNA by these cells was observed after 3 days growth. The synthesis of DNA and RNA was observed before and after culture by means of autoradiographs prepared after exposure to 3H thymidine or 3H uridine. 3H thymidine uptake was low in the initial suspensions and was not increased by the addition of PHA, 3H uridine uptake was increased in only four of 41 cultures stimulated with PHA, and there was a reduction in the number of viable cells in cultures containing PHA.
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.
Effects of Three Mamba Venoms on the Haemostatic Mechanism
Authors: MacKay N. , Ferguson J. C. , McNicol G. P.
Published: March 2008

The venoms of three mambas (Dendroaspis angusticeps, Dendroaspis polylepis and Dendroaspis jamesoni) were shown to be anticoagulant, an effect due largely to interference with the blood thromboplastin mechanism. The venoms were also capable of inhibiting platelet aggregation and reactivity to ADP. All three venoms possessed proteolytic properties but paradoxically reduced euglobulin clot lysis activity. When studied in purified systems this effect was shown to be due to uncompetitive inhibition of plasmin.
Quantitative Histology of Spleen Colonies in Irradiated Mice
Authors: Silini G. , Pons S. , Pozzi L. V.
Published: March 2008

Summary. Quantitative histological examinations were carried out on large numbers of spleen nodules obtained in heavily irradiated mice by injection of bone‐marrow and foetal liver cell suspensions. Endogenous colonies and clones arising from irradiated bone‐marrow cells have also been analysed. It was found that the large majority of clones consisted of cells of either erythroid or myeloid or mega‐karyocytic type. A smaller percentage of clones were mixed with association of the various cell types in all possible combinations. Statistical analysis of the data revealed consistent differences in the distribution of clones derived from various sources. Attention is particularly focused on the mixed clones with a discussion of their significance in the light of the mono‐ or poly‐phyletic origin of blood cells.
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

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

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

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

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

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.
Development of Folate Deficiency in the Rat
Authors: Chanarin I. , Smith G. N. , Wincour Valerie
Published: March 2008

Rats maintained on a folate‐free diet showed the most rapid loss of folate from the liver, followed by a less rapid fall in the serum folate concentration. The slowest decline in folate concentration was found in the red cells.
Vitamin B12 Binding Proteins in Liver Disease
Authors: Retief F. P. , Vandenplas L. , Visser H.
Published: March 2008

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

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

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.
Adenosine Triphosphatase Activity of the Red Cell Membrane in Paroxysmal Nocturnal Haemoglobinuria
Authors: Brabec V. , Mirčevová L. , Palek J.
Published: March 2008

The activity of the ATPase complex of red cell ghosts as well as the activity of the ATPase components, Mg2+ ATPase and Mg2+, Na+ and K+ ‐dependent ATPase was studied in patients with paroxysmal nocturnal haemoglobinuria (PNH). In ghosts prepared by osmotic haemolysis a significantly higher ATPase activity was found in PNH cells than in normal red cells. Ghosts exposed to the effect of saponin showed a significant increase of ATPase activity both in normal and PNH red cells; however, the increase of activity was markedly higher in PNH ghosts than in ghosts of normal red cells. Both Mg2+‐dependent and Mg2+, Na+ and K+‐dependent ATPase contribute to this increase. The protein content in osmotic ghosts of PNH red cells was higher than normal; but after treating these ghosts with saponin, no marked difference in protein content was found.

By comparison with the results of ATPase activity obtained using red cells from non‐splenectomized individuals with hereditary spherocytosis with similar reticulocyte values it is assumed that the increase of ATPase activity is not due to younger cells in the blood but is a further manifestation of the abnormality of the cell membrane in PNH. ATPase activity is present mostly in the inactive form in the red cell membrane and is activated (unmasked) by structural damage of the cell membrane. It is suggested that the increased ATPase activity in the PNH red cell membrane represents a manifestation of abnormal structural arrangement which is more susceptible to damage.

The deviations found in the content and metabolism of organic phosphates are probably caused by the younger population of red cells in PNH.
Experience with a Simplified Method of Radio‐isotopic Assay of Serum Vitamin B12
Authors: Britt R. P. , Bolton F. G. , Cull A. C. , Spray G. H.
Published: March 2008

A simplified method for the assay of serum vitamin B12 by isotopedilution is described. Results obtained by this method correlated well with those obtained by microbiological assay using Lactobacillus leichmannii; reproducibility was of the same order and the range of values obtained in normal subjects fell within the accepted range. There was no difficulty in detecting clinical vitamin B12 deficiency.
Combined Factor‐V and Factor‐ VIII Deficiency: Report of Four Cases
Authors: Seligsohn U. , Ramot B.
Published: March 2008

Three sisters, descendants of a consanguineous marriage, with combined Factor‐V and Factor‐ VIII deficiency, enuresis until early adulthood, and psychopathological manifestations have been reported. The family study, which included three generations, revealed several clinical and laboratory patterns: mild bleeding with normal levels of Factors V and VIII; mild bleeding with mild deficiencies of Factors V and VIII, mild Factor‐V and Factor‐VIII deficiencies without bleeding; neither bleeding nor blood clotting abnormalities. The mode of inheritance of the combined deficiency of Factors V and VIII seemed to be autosomal with complete expression in the homozygous state and partial or no expression in the heterozygous state. This conclusion is in accordance with previous reports. The association of the blood coagulation defect with psychopathological manifestations and enuresis in the present kindred appeared coincidental.

A fourth woman with similar clotting defects but with normal personality is reported from another family. Her parents were also related.

Infusion of fresh haemophilia A plasma to one of the patients in the first family had no effect on Factor‐V and Factor‐VIII levels, but physical effort had a remarkable effect, the levels rising after 24 hours from 16 per cent to 41 per cent and from 0.7 per cent to 32 per cent respectively. In the patient from the other family, only the Factor VIII rose after exercise (from 2.3 to 18.8 per cent), but there was a similar delay in the response.

The technical assistance of Mrs. E. Goldberg is gratefully acknowledged. We are also grateful to Dr. J. Caen for plasma from a known case of Factor‐VII deficiency.
The Free Globin in Human Erythrocytes. I
Authors: Winterhalter Kaspar H. , Heywood J. David , Huehns Ernst R. , Finch Clement A.
Published: March 2008

A method of measuring free globin has been described. Human erythrocytes are shown to contain free globin and levels have been established for a group of haematologically normal individuals. Storage experiments indicate the importance of performing the free globin assay on fresh blood. Evidence is presented that this free globin is probably a mixture of α‐β apoprotein and intermediate α2‐β2 tetramers partially saturated with haem.
The Haematological Effects of Glucose‐6‐Phosphate Dehydrogenase Deficiency and Thalassaemia Trait: Interaction between the Two Genes at the Phenotype Level
Authors: Piomelli S. , Siniscalco M.
Published: March 2008

The haematological effects of glucose‐6‐phosphate dehydrogenase (G6PD) deficiency and thalassaemia trait were evaluated in a field study of 317 individuals in an isolated Sardinian village, where both traits were present at high frequency. G6PD deficiency was diagnosed with rigid genetic criteria. Thalassaemia trait was diagnosed on the basis of abnormal osmotic fragility.

Complete G6PD deficiency resulted in mild anaemia with macrocytosis, a consequence of mild chronic haemolysis. Partial G6PD deficiency had a similar, but less marked effect. Thalassaemia trait resulted in mild anaemia, with marked microcytosis and moderate hypochromia.

The haematological effects of the combination of both traits were equal to the sum of the independent effect of each. The G6PD activity of the individual red cells was similar in thalassaemic and normal individuals. Because of the microcytosis, the G6PD activity per gram of haemoglobin per unit volume of red cells or of whole blood appeared to be elevated in thalassaemia trait.
Alpha‐Thalassaemia in Chinese: Cord Blood Studies
Authors: Todd David , Lai Michael C. S. , Braga Carolina A. , Soo H. N.
Published: March 2008

In an unselected series of 500 umbilical cord blood samples from Southern Chinese infants 15 were found to have from 3.1 to 9.8 (mean 6.5) per cent haemoglobin Bart's. Seven of the 15 were re‐investigated 8–19 months after birth; in six, haemoglobin Bart's was no longer detected while in the remaining one the amount had markedly decreased. Haematological studies, carried out also in some of the parents, indicate that these infants are probably heterozygous for α‐thalassaemia. In the same series one stillborn infant with haemoglobin Bart's hydrops foetalis was encountered.
Nature of the Inhibition of Prothrombin Consumption by Lysed Fibrinogen
Authors: Triantaphyllopoulos D. C. , Chen C. , Triantaphyllopoulos E.
Published: March 2008

The derivatives of the fibrinolytic digestion of fibrinogen which precipitate between 25 and 50 per cent ammonium sulphate saturation inhibit the prothrombin consumption of blood. Disintegration of the platelets by freeze‐thawing or sonication or addition of purified platelet factor 3 did not normalize prothrombin consumption. Normalization occurred after addition of an excess of platelet factor 3 or brain phospholipid. These findings suggest that lysed fibrinogen inhibits the action rather than the release of platelet factor 3. The anticoagulant activity varied neither with the degree of digestion of the parent fibrinogen solution nor with the electrophoretic fraction of the fibrinogen derivatives in contradistinction to the antithrombic effect, which has been shown to depend on these parameters. In purified systems the 25–50 per cent ammonium sulphate fraction of the fibrinogen derivatives retarded the degradation of prothrombin by thrombin and more thrombin activity was found in the two‐stage assay.
Normal Iron Absorption in Hypertransferrinaemic Rats
Authors: Schade Stanley G. , Bernier George M. , Conrad Marcel E.
Published: March 2008

Summary.Iron absorption was studied in rats at intervals after the injection of purified human transferrin. Transferrin did not alter either iron absorption or the red blood cell incorporation of iron in either normal or iron loaded animals. It is unlikely that transferrin regulates iron absorption.
The Decline and Fall of Anti‐Rh(D)
Authors: Hopkins D. F.
Published: March 2008

Summary. Among women immunized to the Rh(D) antigen, the titre of anti‐D measured by the indirect anti‐globulin (TAG) technique falls, on average, to half of the original value in 5–7 years after a pregnancy, but there is a wide range of individual variation. This range is specified. The fall is greater when the initial titre was high. The average titre of saline anti‐D activity falls much more rapidly, although in a minority of individuals this class of antibody persists for many years. The saline anti‐D titre of some women may rise following pregnancy.
A Method of Calculating the Volume of Transplacental Foetomaternal Haemorrhage
Authors: Grobbelaar B. G. , Dunning E. K.
Published: March 2008

Summary. A simple procedure for foetal red cell counting and determining the ratio of foetal red cells to adult red cells is described. Kleihauer's formula for converting the ratio of foetal cells to adult cells into the absolute volume of transplacental haemorrhage was found to give reliable results in a biological trial in which samples of cord blood were injected into 19 patients.
Hypobaric Erythraemia: Pathology and Coagulation Studies*
Authors: Garvey M. Bernadette , Dennis Lewis H. , Hildebrandt Paul K. , Conrad Marcel E.
Published: March 2008

Summary. Rhesus monkeys were made hypoxaemic and erythraemic by caging them in a hypobaric environment simulating an exposure to 17,500 feet above sea level for 28 days. Post‐mortem examination of animals dying during the experiment showed both haemorrhage and thrombosis in the brain and lungs and patchy demyelination in the spinal cord. Coagulation studies showed evidence of accelerated intravascular coagulation which was manifested by marked decreases in blood levels of Factors VIII and IX with less pronounced diminution of Factors V and XI. Platelet counts and the plasma fibrinogen concentration remained normal, but fibrinogen degradation products were found in serum specimens from hypobaric monkeys. Coagulation abnormalities improved following heparin therapy. The coagulopathy seemed more proximately related to erythrocytosis than exposure to the hypobaric atmosphere because coagulation abnormalities were not observed during the first week in an altitude chamber, and they persisted for 2 weeks after removal of the animals from a hypobaric environment. We postulated that the coagulation abnormalities were a manifestation of the hypercoagulable state resulting from increased blood viscosity in the microcirculation.
Diurnal Variations of the Serum Iron in Normal Subjects and in Patients with Haemochromatosis
Authors: Sinniah R. , Doggart J. R. , Neill D. W.
Published: March 2008

Summary. A definite diurnal variation in serum iron exists in normal subjects, in which the serum iron levels are highest in the morning or at noon, and then gradually fall throughout the day to reach their lowest values in the evening; the serum iron concentration rises again the following morning after sleep. The diurnal rhythm may be regulated by the activity of the reticulo‐hypothalamic system, which may be under the influence of neurogenic or hormonal factors. Contrary to other workers, there is a definite diurnal variation in the serum iron concentration in patients with idiopathic haemochromatosis.
Effect of Ethanol on Liver δ‐Aminolaevulinate Synthetase Activity and Urinary Porphyrin Excretion in Symptomatic Porphyria
Authors: Shanley B. C. , Zail S. S. , Joubert S. M.
Published: March 2008

Summary. In a previous study it was found that liver ALA synthetase activity in patients with unequivocal clinical and biochemical evidence of symptomatic porphyria was increased in less than half the patients as compared with a control group which had various forms of hepatocellular disease, but not porphyria. In the present study evidence is presented which shows that hospitalization, and the associated abstinence from alcohol, of patients with symptomatic porphyria results in liver ALA synthetase activity which is no greater than in control groups together with varying degrees of clinical and biochemical remission. When challenged with ethanol, liver ALA synthetase activity increased and uroporphyrin excretion showed a transient rise. It is suggested that ALA synthetase activity and uroporphyrin excretion are related as cause and effect and the role of ethanol is defined as an aggravating factor in this disease.