bluuebunny/crossref_metadata_2025 huggingface dataset:
59Fe Autoradiography of Bone‐Marrow Culture from Normal Subjects and Patients with Uraemia and Pernicious Anaemia*
Authors: Ward H. P. , Tauxe W. N. , Kiely J. M.
Published: March 2008

The kinetics of iron metabolism have been extensively investigated by radioisotopic techniques. In 1961 Pollycove and Mortimer may perhaps have carried the mathematical interpretation of the plasma iron turnover and the red cell incorporation of iron to theoretical limits. However, ferrokinetic studies have been limited by incomplete knowledge of the ‘middle compartment’ of iron metabolism, the bone marrow. Autoradiography with 59Fe offers a direct cytological approach for study of the incorporation of iron into individual normoblasts. Austoni (1956) and Lajtha and Suit (1955) made exploratory observations with this technique in vitro and, recently, Alpen and Cranmore (1959) evaluated erythropoiesis in dogs with 59Fe autoradiography.

It was the purpose of this study to evaluate 59Fe autoradiography in suspensions of human bone marrow and to compare the rate of 59Fe incorporation into normoblasts of normal subjects and patients with pernicious anaemia and the anaemia of chronic renal failure.
Haematological Studies with Methylene Dimethanesulphonate (Dimethanesulphonoxymethane)
Authors: James R. M. V.
Published: March 2008

Studies with the series of sulphonic acid diesters CH3SO2O. (CH2)n. OSO2CH3 (n= 2–10) were originally described by Haddow and Timmis (1953). The n= 4 compound, Myleran, has subsequently become established in the treatment of chronic myeloid leukaemia (Galton, 1956; Haut, Abbott, Wintrobe and Cartwright, 1961). Further studies by Elson (1958) showed Myleran to be the most active member of the series in causing a fall in peripheral blood neutrophils and also the most selective in producing a greater depression of neutrophils than lymphocytes.

The simplest member of the series, methylene dimethanesulphonate (n= 1) has only recently been examined (Fox and Jackson, 1965). The most likely reason for this is that the results of Haddow and Timmis (1953) showed the n= 2 compound to lack myelosuppressive function, thus suggesting inactivity of the n= 1 diester.

The present work was undertaken in order to observe any selective action of methylene dimethanesulphonate on marrow cells and the relation between its effect on peripheral blood neutrophils and granulopoiesis.
Familial Disturbance of Fibrin Monomer Aggregation
Authors: Von Felten A. , Duckert F. , Frick P. G.
Published: March 2008

The investigation of the cause of an accidentally observed prolonged prothrombin time in a patient without a haemorrhagic diathesis led to the discovery of a familial disturbance of the aggregation of fibrin monomers (von Felten, Duckert and Frick, 1965). The observed defect differs from previously reported anomalies in the last phase of coagulation such as congenital afibrinogenaemia or hypofibrinogenaemia (Frick and McQuarrie, 1954), congenital fibrin‐stabilizing‐factor (FSF) deficiency (Duckert, Jung and Shmerling, 1960), and congenital dysfibrinogenaemia (Beck, 1964). It may be similar to the fibrinogen anomaly described by Ménaché (1963).
Methylmalonic Acid Excretion in Vitamin B12 Deficiency
Authors: Bashir Helen V. , Hinterberger H. , Jones B. P.
Published: March 2008

methylmalonic acid was first isolated from pooled human urine in 1957 by Thomas and Stalder and convincing evidence has since been obtained to show that in man the isomerization of l‐methylmalonyl‐Co A to succinyl‐Co A is dependent on the B12 coenzyme dimethylbenzimidazolyl cobamide (White, 1962). Indeed, Cannata, Focesi, Mazumder, Warner and Ochoa (1965) showed recently that l‐methylmalonyl‐Co A mutase bears two molecules of cobamide coenzyme firmly attached to its molecule. In a series of 30 patients Cox and White (1962) detected excessive methylmalonic acid in the urine of all patients with serum vitamin B12 levels below 140 pg./ml., their lower limit of normal. Patients with normal serum B12 levels excreted up to 4 mg. of methylmalonic acid in 24 hours. Their series included six patients who were treated with intramuscular hydroxocobalamin (1000 μg.). In five of these, excretion fell to normal within 3 days, and on the fifth day after injection in the sixth patient. Barness, Young, Mellman, Khan and Williams (1963) reported one vitamin B12 deficient patient in whom the urinary excretion of methylmalonic acid reached 500 mg. in 24 hours. Recently Khan, Williams, Barness, Young, Shafer, Vivacqua and Beaupre (1965) have described seven out of nine patients with pernicious anaemia in whom methylmalonic acid excretion persisted for some months after the institution of B12 therapy. This occurred despite full clinical and haematological remissions and in four patients, normal serum vitamin B12 levels.

The present study was undertaken to determine the value of urinary methylmalonic acid excretion as a screening test for vitamin B12 deficiency. The estimation of methylmalonic acid was carried out by a rapid thin layer chromatographic technique, suitable for routine laboratory use. Normal controls and patients suffering from general haematological and medical disorders were screened as well as patients suffering from megaloblastic anaemia. In several patients the excretion of methylmalonic acid was followed for a short period after B12 therapy.
Giant Myeloid Cells in the Bone Marrow of Protein Malnourished Infants: Relationship to Folate and Vitamin B12 Nutrition
Authors: Spector I. , Metz J.
Published: March 2008

Frank megaloblastic anaemia is well recognized in protein malnourished infants (Altmann and Murray, 1948; Adams, 1954; Walt, Holman and Hendrickse, 1956; Shnier and Metz, 1959; Kho and Tumbelaka, 1960; Macdougall, 1960; MacIver and Back, 1960; Velez, Ghitis, Pradilla and Vitale, 1963). In 1948, Altmann and Murray noted that in this syndrome, giant myeloid cells may occur in the bone marrow without megaloblasts, a finding subsequently confirmed by other workers (Walt et al., 1956; Macdougall, 1960; Sandstead, Gabr, Azzam, Shuky, Weiler, El Din, Mokhtar, Prasad, El Hifney and Darby, 1965). These giant myeloid cells have been regarded as diagnostic of deficiency of haemopoietic factor (liver principle) as are megaloblasts themselves (Foy, Kondi and Murray, 1946; Zuelzer and Ogden, 1946). Zuelzer, Newhall and Hutaff (1947) postulated that giant myeloid cells were the earliest morphological sign of such deficiency, a view accepted by others (Foy, Kondi and Hargreaves, 1950; Luhby, 1959; MacIver and Back, 1960; Dawson and Bury, 1961), so that these cells are regarded as a sensitive index of early megaloblastic change. Since these views were expressed, serum levels of the anti‐megaloblastic factors, vitamin B12 and folate, have gained wide acceptance as sensitive indices of body nutrition of these vitamins (Spray and Witts, 1958; Herbert, Baker, Frank, Pasher, Sabotka and Wasserman, 1960; Waters and Mollin, 1961). The present study of protein malnourished infants was undertaken to determine the relationship between giant myeloid cells in the bone marrow and folate and vitamin B12 nutrition, by measuring the serum levels of these vitamins and observing the effect of their administration on the presence of these cells in the marrow. As iron deficiency has been shown to be a factor in the development of giant myeloid cells in the marrows of pregnant patients (Chanarin, Rothman and Berry, 1965), the marrow films were also examined for a possible correlation between diminished amounts of stainable iron and the presence of giant myeloid cells.
Iron Absorption in Relation to Transferrin Saturation and Other Factors
Authors: Taylor M. R. H. , Gatenby P. B. B.
Published: March 2008

Attempts have been made in the past to relate iron absorption to the results of blood and serological tests. Pirzio‐Biroli and Finch (1960) looked, without success, for relationships between iron absorption and age, sex, haematocrit, reticulocyte count, plasma iron and marrow iron. Shultz and Smith (1958) using 59Fe labelled eggs, found relationships between iron absorption and age (r=−0.2892), serum iron (r=−0.2430) and haemoglobin concentration (r=−0.1545), in 90 normal children. Wheby and Umpierre (1964) found that saturation of a subject's transferrin by intravenous iron made little difference to the amount of iron absorbed as compared to a control test on the same subject, although the site of deposition of the iron was affected.

A study was undertaken to see if there was any relationship between iron absorption and the results of blood and serological tests with special reference to anaemia. In the past, workers have segregated subjects into ‘‘iron deficient’ and ‘normal’ taking some arbitrary dividing line. This is an artificial division. Many cases of iron deficiency develop slowly from persistent iron loss or dietary deficiency, so that many stages between iron repletion and severe iron deficiency are to be found. The subjects in this study were considered as a single group, some being severely iron deficient and anaemic, and others being apparently normal. It was thought that this approach would be more likely to show up any relationships which were present, than would an analysis which involved arbitrary grouping of the subjects.
Factor‐VIII (Antihaemophilic Factor) Activity in Sickle‐Cell Anaemia
Authors: Abildgaard C. F. , Simone J. V. , Schulman I.
Published: March 2008

Sickle‐cell anaemia was found to be associated with elevated Factor‐VIII activity in the absence of significant elevation of other coagulation factors. Factor VIII was normal in individuals with sickle‐cell trait except during pregnancy. Following multiple transfusions Factor‐VIII levels fell to within the normal range in three patients with sickle‐cell anaemia. No relationship between Factor‐VIII level and painful crisis was noted. It is suggested that the elevation of Factor VIII is directly related to the degree of haemolysis.
The Anaemia of Erythropoietic Porphyria
Authors: Zail S. S. , Krawitz P. , Viljoen E. , Kramer S.
Published: March 2008

A case of congenital erythropoietic porphyria was found to have an intermittent haemolytic anaemia. During the haemolytic phase, red‐cell lysates from the patient made type I coproporphyrin on incubation with ALA. In the phase of non‐haemolysis, red‐cell lysates behaved as normal cells, only type III coproporphyrin being produced. There is thus a relationship between haemolytic anaemia in this disease and the disturbance in the uroporphyrinogen isomerase‐porphobilinogen deaminase enzyme complex in the red cell. Red‐cell glucose utilization, ATP stability on incubation of red cells, glutathione and glutathione stability, and glutathione reductase activities showed no abnormalities. The glucose‐6‐phosphatase dehydrogenase activity was slightly increased.
The Inhibition of Anaerobic Glycolysis in Red Cells by Leukaemic Leucocytes
Authors: Sabine Jean C.
Published: March 2008

Rates of anaerobic glycolysis were determined simultaneously in the red cells and leucocytes of patients with malignant haematologic disorders. The disappearance of glucose and the evolution of CO2 from bicarbonate were measured in the same Warburg flasks over the same period of time.

In four patients with lymphogenous leukaemia and in one with acute leukaemia of disputed type but probably myelogenous, the leucocytes suppressed the glycolytic activity of the red cells. This abnormal finding appeared with exacerbation of the disease and disappeared with remission. It was present during the terminal phase in four patients, but could not be attributed to the presence of blast cells in the peripheral blood.

The leukaeinic leucocytes exerted the same inhibitory effect on normal donor cells as on those of the patient. The plasma and the supernatant fluid from strongly inhibited reactions were without effect, as were aqueous and hypertonic extracts of the leucocytes. In all Warburg reactions the rate was constant, with no evidence of a cumulative effect. The inhibition was reversed by removal of the leucocytes.

The characteristics of this phenomenon resemble molecular behaviour and suggest an equilibrium of some kind. Its kinetic properties closely resenible those of stoichiometric inhibition of an enzyme system. It is conjectured that an intercellular stress, perhaps physicochemical in nature, may have been exerted between the leucocytes and red cells, temporarily interfering with some event in thc glycolytic cycle of the latter.
Hereditary Elliptocytosis: A Report of Two Families from New Guinea
Authors: Pryor D. S. , Pitney W. R.
Published: March 2008

Two New Guinea families with hereditary elliptocytosis are reported. All four parents demonstrated elliptocytes in blood films and the two fathers also had deficiency of red‐cell glucose‐6‐phosphate dehydrogenase activity. The parents of one family showed normal red‐cell survival, while there was evidence of increased red‐cell destruction in the parents of the other family. One child in each family had severe haemolytic anaemia and it is suggested that these were possibly homozygous for elliptocytosis. Splenectomy was performed in one case and resulted in clinical and haematological improvement.

Red‐cell osmotic fragility curves performed on members of both families showed some differences from the patterns previously reported in hereditary elliptocytosis.
Physiology of the Regulation of Platelet Production
Authors: de Gabriele Geswalda , Penington D. G.
Published: March 2008

Platelet production is stimulated by removal or destruction of platelets and is inhibited by hypertransfusion with viable platelets. It is not influenced by factors regulating red cell production, even in the absence of the spleen. Nephrectomy does not impair the response to platelet depletion. It is concluded that the regulation of platelet production is by a system entirely independent of that governing erythropoiesis.
Accumulation of Iron in Mitochondria of Erythroblasts
Authors: Goodman J. R. , Hall S. G.
Published: March 2008

Abnormal accumulations of iron in the mitochondria of erythroblasts were observed in patients who developed mild transitory anaemia while on a course of chloramphenicol and in patients with porphyria cutanea tarda. These and similar observations in six other syndromes were the basis for a discussion of the biochemical aetiology of this increased deposition of iron.
Haematological Effects of the Idiopathic Splenomegaly Seen in Uganda
Authors: Richmond J. , Donaldson G. W. K. , Williams R. , Hamilton P. J. S. , Hutt M. S. R.
Published: March 2008

The haematological effects of idiopathic splenomegaly have been studied in a group of 15 Ugandan patients. The results of the main investigations were compared with those obtained in five patients with miscellaneous diseases and without palpable splenomegaly.

The splenic enlargement was mainly due to reticuloendothelial hyperplasia and not to sinusoidal congestion.

A normochromic anaemia was present in almost all the patients and a proportion had leucopenia and thrombocytopenia. One patient presented with a crisis of anaemia; she was later shown to have red cell G6PD deficiency which was believed to be coincidental.

Three aetiological factors were found in relation to the anaemia; reduction of red cell survival time, present in all the patients, haemodilution from expansion of the plasma volume, and the exclusion of a proportion of the red cell mass from the general circulation by the spleen. Six to 39 per cent of the red cell volume, the amount varying with spleen size, was sequestered in a slow mixing compartment, believed to be the extrasinusoidal spaces (the spleen pool) in the patients with splenomegaly. No spleen pool could be shown in any of the patients without splenomegaly.

Intrasplenic red cell destruction was not conspicuous and it has been suggested that the red cells, after damage from repeated stagnation in the spleen pool, are destroyed widely throughout the body.

The reasons for expansion of the plasma volume is not known. It relates to spleen size but cannot wholly be explained by plasma in the spleen pool.

A good result from splenectomy was obtained in six out of seven patients in whom this was undertaken. Two months after operation the red cell survival time was corrected in the patients in whom this was measured. The rise in the PCV could be explained only by substantial reduction in plasma volume.
Serum Folic Acid Levels in Pregnancy and their Relationshi to Megaloblastic Marrow Change
Authors: Temperley I. J. , Meehan M. J. M. , Gatenby P. B. B.
Published: March 2008

Summary In a prospective study of a randomly selected group of pregnant women it has been shown that the mean serum folic acid level falls as pregnancy advances and that 3 months after delivery the level has not reached that of non‐pregnant women in the child bearing age.

Low serum folic acid levels at the first visit and subsequently throughout pregnancy were observed in 15 patients who developed megaloblastic erythropoiesis at or near term. The haemoglobin level at term of patients with a low folic acid level at the first visit was significantly lower when compared with those with a higher initial level.

The duration of low serum folic acid levels, and its relation to subsequent marrow change towards full megaloblastosis is discussed.
Red Cell Fatty Acids in Polycythaemia Vera
Authors: Dhopeshwarkar G. A. , Sukhatankar Usha N.
Published: March 2008

Summary Total lipids of red cells as well as plasma from polycythaemia Vera patients and normal subjects were fractionated and the fatty acid composition was analysed by gas‐liquid chromatography. The following statistically significant differences were found in the percent fatty acid levels.

Red cell. Linoleic acid level of total lipids was decreased in polycythaemia whereas oleic acid level of phospholipid fractions was increased. Stearic acid level of cholesterol ester fraction was increased in polycythaemia whereas that of triglyceride fraction was decreased. Significantly low levels of arachidonic acid associated with cholesterol ester fraction were noted in polycythaemia patients.

Plasma. Palmitic acid associated with total lipids and oleic acid levels of phospholipid fractions were higher in polycythaemia. Stearic acid associated with phosphatidyl ethanolamine was found to be decreased in polycythaemia. Similarly arachidonic acid associated with total lipids as well as sphingomyelin was decreased in polycythaemia. A wide difference between the lipids of the red cell and the surrounding plasma was observed.
The Effect of Splenectomy on the Leucocyte Count
Authors: McBride J. A. , Dacie J. V. , Shapley R.
Published: March 2008

Summary The effect of splenectomy on the peripheral blood leucocyte count has been studied in patients suffering from various types of hereditary haemolytic anaemias and in haematologically normal individuals. In each group of patients studied there was a marked increase in the total leucocyte count, and in the lymphocyte and monocyte counts, 3 months or more after splenectomy. The neutrophil count was also increased but to a lesser degree. The number of leucocytes of all categories in the peripheral blood did not seem to be influenced by the presence of anaemia persisting after splenectomy.
Haemoglobin F Texas II (α2γ26 Glu→Lys), the Second of the Haemoglobin F Texas Variants
Authors: Larkin I. L. M. , Baker T. , Lorkin P. A. , Lehmann H. , Black A. J. , Huntsman R. G.
Published: March 2008

Summary A survey of 13,000 cord bloods in Great Britain yielded an electrophoretically abnormal variant of Haemoglobin F which resembled Haemoglobin F Texas. Haemoglobin F Texas might be either α2γ25G1u→Lys or α2γ26Glu→Lys. The first has been described and was named Haemoglobin F Texas I. The present variant has the same substitution in the sixth residue of the γ chain and is designated as Haenioglobin F Texas II.
A Simple Method for the Assay of Factor VIII, Using 20 Microlitres of Capillary Blood
Authors: Vermylen C. , Verstraete M.
Published: March 2008

Summary A simple and sensitive method for Factor‐VIII assay is presented which permits a reproducible quantitative assay on 20μl. capillary blood.
A Mathematical Analysis of Red Blood Cell and Bone Marrow Stem Cell Control Mechanisms
Authors: Kirk J. , Orr J. S. , Hope C. S.
Published: March 2008

The oscillations, interactions and control mechanisms of the red blood cell and bone marrow stem cell system were studied. A mathematical formulation in the form of four difference‐differential simultaneous equations was established in the four variables of the system; (i) stem cell population, (ii) chalone mitotic inhibitor, (iii) red cell population, and (iv) erythropoietin; as postulated by Orr, Kirk, Gray and Anderson (1968). Numerical values of the constants in these equations were determined from a large range of data.

Calculations on the behaviour of the formulation were carried out using an ICT 1902 digital computer. The predictions of the formulation were compared with three kinetic sets of experimental data, showing satisfactory agreement. Analysis of the system yields the value of the stem cell population. In conclusion, some properties of the oscillatory features of the system are discussed.
Localization of 5‐Hydroxytryptamine in Blood Platelets: An Autoradiographic and Ultrastructural Study
Authors: Davis Richard B. , White James G.
Published: March 2008

5‐Hydroxytryptamine (serotonin, 5‐HT) was found by electronmicroscope autoradiography to be localized in dense granules in platelets. Evidence of radioactivity from tritium‐labelled 5‐HT was also found at other sites within platelets, but without evidence of concentration at those sites. Studies on human platelets showed that the dense granules were present in different forms, and structural evidence suggested that the dense granules containing 5‐HT may be derived from alpha granules. After clotting of platelet‐rich plasma, and before the structural integrity of the platelets was lost, radioactivity was present in relation to dense granules, but had been lost from other sites, suggesting firmer binding of 5‐HT to the granules.
Alkaline Phosphatase Activity in Immature Granulocytes
Authors: Malasková Věra , Fuksová Jiřina
Published: March 2008

A positive reaction for alkaline phosphatase activity in granulocyte precursors (myelocytes, promyelocytes and even some blast cells) has been observed in three patients. Two of them had a blastic crisis of subacute or chronic myeloid leukaemia. In the third patient with a blastic crisis of a myeloproliferative syndrome, AP activity was unusually high in pseudo‐Pelger forms of neutrophils from the myelocyte stage onwards. All other cytochemical reactions were normal and in accordance with the myeloid character of the blast cells. The nature of the cells involved and possible explanations of this unusual finding are discussed.
Hepatic δ‐Aminolaevulinic Acid Synthetase Activity in Symptomatic Porphyria
Authors: Zail S. S. , Joubert S. M.
Published: March 2008

Hepatic ALA synthetase activity was determined on biopsy material from 12 patients with symptomatic porphyria. Five patients had values at least 1.5 times greater than the highest normal value whilst the remaining seven had values within or slightly above the highest normal value. No correlation was observed between ALA synthetase activity and urinary or stool porphyrin excretion. The metabolic significance of this finding is discussed.
Studies on the Incorporation of 14C‐Sodium Acetate into the Phospholipids of Phytohaemagglutinin‐Stimulated and Unstimulated Lymphocytes
Authors: Huber H. , Strieder N. , Winnler H. , Reiser G. , Koppelstaetter K.
Published: March 2008

The in vitro incorporation of 14C‐acetate into the phospholipids of unstimulated and phytohaemagglutinin (PHA)‐stimulated lymphocytes and the distribution of radioactivity in the phospholipid fractions, separated by thin‐layer chromatography, have been studied in lymphocyte cultures.

The percentage of radioactive incorporation into the phospholipid fractions of PHA‐stimulated lymphocytes was as follows: lysolecithin 4.0 (± 1.3), sphingomyelin 12.7 (± 1.4), lecithin 39.2 (± 2.0), phosphatidyl‐serine and phosphatidyl‐inositol 14.1 (± 2.1), phosphatidyl‐ethanolamine 28.5 (± 2.0). The percentage of radioactive incorporation into the phospholipid fractions of unstimulated lymphocytes was: lysolecithin 7.9 (± 1.4), sphingomyelin 8.2 (± 1.4), lecithin 34.5 (± 2.6), phosphatidyl‐serine and phosphatidyl‐inositol 14.5 (± 1.3), phosphatidyl‐ethanolamine 31.4 (± 1.4).

The results of the lipid‐phosphorus distribution (n= 4) were similar and showed differences only in the sphingomyelin fraction (P<0.05). With a given initial cell number, the radioactive incorporation into the phospholipid fractions of PHA‐stimulated lymphocytes was increased by the following factors: lysolecithin 3.9 (± 0.6), sphingomyelin 7.0 (± 1.5), lecithin 8.1 (± 1.5), phosphatidyl‐serine and phosphatidyl‐inositol 8.8 (± 1.3), phosphatidyl‐ethanolamine 7.3 (± 0.8).

Cell‐fractionation experiments with PHA‐stimulated lymphocytes after labelling with 3H‐acetate showed a similar distribution of the radioactivity in the phospholipids of ‘mitochondria’and ‘microsomes’.
The Effect of Acute Anaemia on Platelet Adhesiveness before and after Splenectomy in the Rabbit
Authors: McBride J. A. , Wright H. Payling
Published: March 2008

Platelet count and platelet adhesiveness were measured in groups of rabbits made anaemic by chemical haemolysis or by haemorrhage both before and after splenectomy. When platelet adhesiveness was corrected for changes in the PCV, a significant increase in adhesiveness was found on the 3rd and 10th days after the induction of anaemia.

After splenectomy, platelet adhesiveness was marginally but apparently permanently increased.

During acute haemolytic episodes there was no relationship between the platelet count and PCV in splenectomized rabbits.
Pernicious Anaemia and Polycythaemia Rubra Vera
Authors: England J. M. , Chanarin I. , Perry Janet , Szur L.
Published: March 2008

Forty patients with pernicious anaemia and polycythaemia vera have been described. In order to determine whether this association was due to an autoimmune mechanism or to chance, the frequency of parietal cell antibodies was estimated in 51 patients with polycythaemia. The incidence of parietal cell antibodies in these patients was similar (8 per cent) to that in a matched control group (6 per cent).
Mechanism of Excretion of Iron by the Small Intestine: an Experimental Study in Rats with Normal and Abnormal Mucosae
Authors: Singh A. K. , Loehry C. A.
Published: March 2008

The findings in the present study have demonstrated the presence of two distinct mechanisms of iron excretion by the small intestine in rats. Loss of cell bound iron is the principal pathway of excretion and takes place as epithelial cells are shed off from the tips of villi. The available evidence suggests that the epithelial cells of the mucosa sequestrate iron from a storage pool which might be identical to the labile iron store in man. Transferrin bound iron makes a small contribution to the total loss. An abnormally large amount of iron was excreted in the small intestine of rats infested with Nippostrongylus brasiliensis. At the same time an unduly large amount was also sequestrated by the intestines of these rats. These facts were attributed to increased population of maturing cells in the crypts and the rapid rate of renewal of the villous epithelium.

The morphological appearances of the intestinal villi of the infested rats have a resemblance to those in human subjects with coeliac disease. It is, therefore, suggested that these observations may have some bearing on the status of iron balance in patients suffering from coeliac disease.
Hereditary Haemolytic Anaemia due to an Abnormal Haemoglobin (Haemoglobin Kings County)
Authors: Sathiapalan Rugmini , Robinson Margaret G.
Published: March 2008

Two patients in an American Negro family with a hereditary non‐spherocytic haemolytic Heinz‐body anaemia, mesobilifuscinuria, and an abnormal haemoglobin have been studied. The absence of any abnormality in the red cell metabolism and the presence of a thermolabile fraction of the haemoglobin constituting 10 per cent of the patients’total haemoglobin make us believe that the cause of the haemolysis is the abnormal haemoglobin. Since this haemoglobin appears to differ from all the other abnormal haemoglobins described in patients having congenital non‐spherocytic haemolytic anaemia, a new name (haemoglobin Kings County) is proposed for it.
Effect of Phenothiazine on the Red Cells of Paroxysmal Nocturnal Haemoglobinuria
Authors: Laforet Mitsuko Tashiro , Gardner Frank H.
Published: March 2008

Summary. A phenothiazine derivative (chlorpromazine hydrochloride) was investigated as a possible means of reducing the transfusion requirement of patients with paroxysmal nocturnal haemoglobinuria. Results of in‐vitro studies have indicated that the drug has both beneficial and detrimental effects on the PNH red cell. Thus, while the osmotic haemolysis time is increased and the degree of acid haemolysis (Ham's test) is decreased, the osmotic fragility is increased on incubation. An in‐vivo survival study of ficin‐treated rabbit red cells showed no beneficial effect when the rabbits were primed with phenothiazine. It is therefore suggested that whenever drugs of the phenothiazine family are used, it should be with an awareness of potential haemolytic side effects in PNH and possibly in other haemolytic disorders.
Measurement of a Labile Iron Store
Authors: Singh A. K.
Published: March 2008

Summary. A method for the quantitative measurement of a labile iron store has been described. The validity of the method was established by demonstrating quantitative differences between normal individuals, patients with iron deficiency and patients with iron overload. The method does not measure total body iron, but appears to give reproducible estimates of a labile fraction. Evidence has also been presented to show that the iron present in this labile store is immediately available for haemoglobin synthesis and that iron derived from immediate haemoglobin breakdown enters this labile iron store.
Folate Activity in Reticulocytes and the Incorporation of Tritiated Pteroylglutamic Acid into Red Cells
Authors: Izak G. , Rachmilewitz M. , Grossowicz N. , Galewski K. , Kraus Sh.
Published: March 2008

Summary. Reticulocytes produced by repeated phenylhydrazine injections in rabbits and rats showed markedly increased folate activity as compared with that of mature red cells. Reticulocytes incorporated larger amounts of tritiated pteroylglutamic acid than mature red cells of rabbits, rats, and of one human subject. Marked quantitative differences were observed between the ability of the red cells of these three species to take up folate.
Erythropoietin and Haemoglobin Studies on AKR Mice
Authors: Lewis Jasper P. , Alford Dorothy A. , Smith James E. , Horton Bennett F. , Smith Linda L.
Published: March 2008

Summary. DEAE‐Sephadex column chromatography has been used to study the haemoglobins of AKR untreated mice, polycythaemic mice injected with saline and polycythaemic mice treated with an extract of human erythropoietin. All elution patterns of the haemolysates showed four haemoglobins. The haemolysates of each group had an elution pattern different from the other groups. Chromatographic studies of an ageing haemolysate indicated the formation of a minor haemoglobin from a major haemoglobin to be linear for a period of about 18 days.

The major AKR mouse haemoglobin appeared to polymerize, possibly to octaniers. Human erythropoietin, when injected into polycythaemic mice, seemed to decrease the resulting polymerization of the major haemoglobin and the formation of the minor haemoglobin. Treatment of the haemolysates with reduced glutathione seemed to depolymerize the polymers to tetramers. An extract of human erythropoietin lowered the glutathione level in the blood of an AKR strain of mice.
Hereditary Persistence of Foetal Haemogloblll in a Thai Family: The First Instance in the Mongol Race and in Association with Haemoglobin E
Authors: Wasi P. , Pootrakul S. , Na‐Nakorn S.
Published: March 2008

Summary. Hereditary persistence of foetal haemoglobin is described in a Thai family. The AF heterozygotes were healthy and had normal haematological findings except the decrease in haemoglobin A2 level and the presence of a large amount of haemoglobin F. The latter, comprising 21–22 per cent, is higher than in the Greek but lower than in the Negro counterparts. Three persons, who were heterozygous for both haemoglobin E and high F genes, were not anaemic but had numerous target‐erythrocytes; haemoglobin E constituted 40 per cent, the rest being haemoglobin F. Acid‐elution staining revealed haemoglobin F in every red cell in both AF and EF heterozygotes. The absence of haemoglobin A in the latter suggests allelism between this type of hereditary persistence of foetal haemoglobin and haemoglobin E or β‐structural gene.
Extracorporeal Irradiation of the Blood in Leukaemic Patients
Authors: Lajtha L. G. , Garrett J. V. , Turner L. , Gilbert C. W. , Halnan K. E. , Easson E. C. , Nuttall P. M. , Watson‐Williams E. J. , Keidan S. E.
Published: March 2008

Fourteen short treatment courses of extracorporeal irradiation have been given to 13 patients; eight had acute leukaemia, one had chronic myeloid leukaemia in the acute terminal phase, and four had chronic lymphocytic leukaemia.

Five of the patients with acute leukaemia were treated relatively early in the disease; they responded with a reduction in the blast‐cell count in the blood which was maintained with chemotherapy. In the chronic lymphocytic leukaemia cases, the white‐cell count and the size of the spleen and lymph nodes were reduced, with clinical improvement in three cases.

Dosage and theoretical considerations have been discussed and it is considered that there is no evidence that a significant interchange of cells between the blood and the bone marrow occurs in acute leukaemia. The results in the treatment of certain cases of early acute leukaemia and late chronic lymphocytic leukaemia warrant further trials.
Congenital Thrombocytopenia with Giant Platelets: a Defect in the Platelet Membrane
Authors: Gröttum Kjell A. , Solum Nils Olav
Published: March 2008

Three patients with congenital macrothrombocytic thrombocytopenia are described. The platelets had a reduced electrophoretic mobility, and the content of sialic acid was also abnormally low, suggesting a defect in the platelet membrane. Platelets were rapidly removed from the circulation, possibly because the platelet membrane defect was associated with reduced electrostatic repulsive forces.
Activated Coagulation Factors: In‐Vivo and in‐Vitro Studies
Authors: Niemetz J. , Nossel H. L.
Published: March 2008

In the course of serial coagulation studies on patients with acute leukaemia, defibrination was frequently encountered in the lymphoblastic, myeloblastic and promyelocytic varieties of the disease. Factor‐VIII levels were often high and varied very considerably, a particular phenomenon being the association at times of very high one‐stage levels with decreased two‐stage levels. In one patient heparin infusion was associated with a rise in the two‐stage Factor‐VIII level and cessation of the infusion with a prompt drop in level. Less frequently, gross elevation of one‐stage Factor‐XI activity occurred compared with two‐stage (eluate test) levels. In order to study possible mechanisms for the phenomena observed, the effect of adding various pro‐coagulants to normal plasma on the one‐ and two‐stage methods for measuring Factors VIII, IX and XI was studied. Thrombin caused a marked rise in one‐stage Factor‐VIII activity and a much smaller rise in one‐stage Factor IX and XI measurements. Two‐stage Factor‐VIII activity was reduced and Factors IX and XI little affected. These findings simulate some of the findings in vivo. The effect of activated Factors IX, X and XI on the one‐stage activity of Factors VIII, IX and XI may be explained by assuming that an activated product increases the one‐stage activity of any factor which participates in the clotting reaction sequence at a stage preceding the formation of the product. The actual findings were that an activated Factor‐X preparation increased one‐stage Factors VIII, IX and XI measurements; an activated Factor‐IX preparation considerably increased one‐stage Factor IX and XI measurements but affected Factor‐VIII activity only when used at very high concentrations; an activated Factor‐XI preparation did not affect Factor VIII, IX or XI one‐stage activity. None of these three activated products influenced the two‐stage measurements of Factors VIII, IX and XI. Tissue thromboplastin increased one‐stage Factor VIII, IX and XI activity to a similar extent, did not influence two‐stage Factor VIII and IX measurements and slightly increased two‐stage Factor‐XI activity.
Effect on Red Cells of a Small Rise in Temperature: in Vitro Studies
Authors: Karle Hans
Published: March 2008

An increased destruction of red cells was previously demonstrated during experimental fever. The present study deals with the changes in red cells produced by extended exposure in vitro to temperatures in the biological range of fever.

By elevating the temperature only a few degrees above normal body temperature a distinct increase in spontaneous haemolysis and osmotic fragility of rabbit red cells was observed. By combination of exposure to heat in vitro and survival‐studies in vivo, using red cells labelled with 51Cr or 59Fe, it was confirmed that even small elevations of temperature greatly reduced the survival of the red cells in the circulation. In a supplementary investigation in rabbits a significant increase in osmotic fragility was observed during experimentally produced fever using injections of bacterial pyrogen or external heating.

No difference in glucose consumption during incubation of red cells in vitro at normal and elevated temperature could be demonstrated and inactivation of vital enzymes seems not to be responsible for the injury to the cells. Other mechanisms, especially the possibility of changes in the lipoprotein structure of the cell membranes, are discussed.

In a single study, human red cells exhibited the same vulnerability as rabbit red cells to small elevations of temperature, although their sensitivity was less.
Observations on the Mechanism of Action of Acetylphenyl‐hydrazine in Normal and Glucose‐6‐Phosphate Dehydrogenase (G‐6‐PD) Deficient Erythrocytes
Authors: Stuart Gary A.
Published: March 2008

Evidence is presented that two mechanisms of action account for the GSH instability of G6‐PD‐deficient erythrocytes following incubation with acetylphenylhydrazine. In Mechanism A, also manifested by the normal cell, acetylphenylhydrazine has the characteristics of an inhibitor which stoicheiometrically prevents the maintenance of an amount of GSH proportional to the dose of the drug. In Mechanism B the effect of acetylphenylhydrazine is proportional to the red cell concentration indicating an excess of the drug relative to its site of action. The loss of GSH by both mechanisms is related to the severity of the G‐6‐PD deficiency.

Additional experiments show that mechanisms of action similar to those exhibited by the G6‐PD‐deficient erythrocyte exist in the normal red cell suspended in a galactose solution or in solutions containing low quantities of glucose.
Macrocytosis in Patients on Anticonvulsant Drugs
Authors: Child J. A. , Khattak B. Z. , Knowles J. P.
Published: March 2008

Blood from 100 patients taking anticonvulsant drugs was examined and a high mean cell volume (MCV) was found in 8 per cent, a low folate in 27 per cent and macrocytosis on a peripheral blood smear in 18 per cent. In 10 of 11 patients with a high or high‐normal MCV, there was a fall in MCV following treatment with oral folic acid; there was no increase in the frequency of convulsions and an improvement in mental condition was noted in five of the 11 cases. It is suggested that, whereas minor disturbances of folic‐acid metabolism may be common in patients taking anticonvulsant drugs, when a major dyscrasia occurs, additional factors, for example dietary deficiency, should be sought.
Immunochemical Classes of Myelomatosis. INCLUDING DATA FROM A THERAPEUTIC TRIAL CONDUCTED BY A MEDICAL RESEARCH COUNCIL WORKING PARTY*
Authors: Hobbs J. R.
Published: March 2008

A study of the clinical and biochemical features of myelomatosis according to the immunochemical class of paraprotein found has revealed statistically significant difference between the classes. These are reviewed but it is stressed that they are chiefly of importance when comparing groups of patients.
Absence of Plasma Transamidase Activity in Congenital Deficiency of Fibrin Stabilizing Factor (Factor XIII)
Authors: Miloszewski K. , Walls W. D. , Losowsky M. S.
Published: March 2008

Summary. Plasma from normal individuals incorporates 14C‐labelled glycine ethyl ester into casein. The incorporation of glycine ethyl ester into casein was directly proportional to the time of incubation and to the amount of normal plasma present. Plasma from patients with known congenital deficiency of Factor XIII did not incorporate 14C‐labelled glycine ethyl ester into casein, suggesting that transamidase activity represents the action of Factor XIII in the formation of normal plasma clot.
The Inhibition of Activated Factor X with Di:isopropyl Fluorophosphate
Authors: Leveson J. E. , Esnouf M. P.
Published: March 2008

Summary. The esterase and coagulant activities of activated Factor X have been inhibited by radioactive di:isopropyl fluorophosphate. The amino acid sequence about the site of binding of the di:isopropyl moiety has been shown to be gly.asp.ser‐P‐gly.
Reticulated Platelets following Acute Blood Loss
Authors: Ingram M. , Coopersmith A.
Published: March 2008

Summary. This report describes a previously unreported type of platelet released into the peripheral blood of dogs following acute blood loss. These cells display coarse, punctate condensations (reticulum) when stained supravitally with new methylene blue, and are probably analogous to reticulated erythrocytes. Both types of reticulated cells occur in increased numbers following acute blood loss.
The Effect of Ascorbic Acid Deficiency on Desferrioxamine‐Induced Urinary Iron Excretion
Authors: Wapnick A. A. , Lynch S. R. , Charlton R. W. , Seftel H. C. , Bothwell T. H.
Published: March 2008

Summary. The levels of tissue ascorbic acid tend to be low in subjects with iron overload. The present study was undertaken to find out whether this ascorbic acid deficiency affected the quantities of iron excreted in the urine after the administration of the iron chelate, desferrioxamine. Basal tests were done and were then repeated after 7 days of ascorbic acid therapy. Desferrioxamine‐induced urinary iron excretion increased by 88 per cent in 13 individuals with transfusional siderosis, 60 per cent in five with idiopathic haemochromatosis and 350 per cent in 12 Bantu subjects with dietary siderosis. Over the same period the mean leucocyte ascorbic acid concentrations rose by 164 per cent, 157 per cent and 551 per cent respectively. In contrast, no change was noted in either urinary iron excretion or in ascorbic acid concentrations in six normal white and six normal Bantu control subjects. These results suggest that tissue ascorbic acid concentrations should be restored to normal before desferrioxamine is used for either the diagnosis or the treatment of iron overload.
Morphological‐Biochemical Correlations in Rabbit Red Cell Precursors Synchronized by Actinomycin Administration
Authors: Hershko Ch. , Schwartz R. , Izak G.
Published: March 2008

Summary. By making use of the selective toxicity of Actinomycin D, homogenous erythroid populations of various stages of maturation had been obtained in the rabbit. Comparison of the morphological characteristics of red cell precursors with in vitro synthetic activity as measured by the rate of incorporation of 32P, 59Fe and [2‐14C]glycine into DNA, RNA, haem and protein respectively, revealed the following:

The rate of haem synthesis was negligible in pronormoblasts and early basophilic normoblasts, highest 1 day after Actinomycin administration, i.e. corresponding to a more advanced stage of erythroid maturation, and again lower in orthochromatic normoblasts.

The rate of RNA synthesis was extremely low in the first 2 days following exposure to Actinomycin D. While our data could not permit distinction between interference of the drug with DNA‐dependent RNA synthesis and a spontaneous loss of RNA synthetic activity brought about by maturation, it was clear that this reduction in RNA synthesis did not affect the rate of protein synthesis. This observation lends further support to earlier claims for the existence of a stable messenger RNA in erythroid cells.

Proliferation of undifferentiated mononuclear cells preceded the restitution of bone marrow population after the toxic action of Actinomycin D. Factors affecting their in vitro differentiation are currently being investigated in our laboratory.
Organ Distribution of Fibrin in Disseminated Intravascular Coagulation
Authors: Regoeczi E. , Brain M. C.
Published: March 2008

Summary.

The quantitative distribution of 131I‐fibrin in the organs and tissues of rabbits with inhibition of fibrinolysis was compared following the injection of the purified coagulant enzyme of Agkistrodon rhodostoma venom (Arvin) or the infusion of thrombin.

There was virtually complete conversion of fibrinogen to fibrin by both Arvin and thrombin, although the rate of conversion was three times as fast with Arvin.

67–79 per cent of the radioactive fibrin was present in the kidneys, lungs, liver and bone marrow. After Arvin most fibrin (33 per cent) was present in the lungs, but after thrombin most fibrin (24 per cent) was in the kidneys.

It is suggested that the distribution of fibrin between the organs may be dependent on the speed of fibrin formation and hence the size of microdot formed. The large accumulation of fibrin in the kidneys after thrombin may reflect the well‐recognized clinical association between disseminated intravascular coagulation and impaired renal function.
The Haemoglobin Concentration of Peripheral and Central Blood of the Laboratory Rat
Authors: Doell B. H. , Hegarty P. V. J.
Published: March 2008

Precise details of the method of blood collection for haemoglobin analysis from laboratory rats are seldom given in published work. In this paper, haemoglobin values of blood collected from the tail and from the heart of rats of various sizes fed different diets were compared. Lower haemoglobin concentrations were found in heart blood than in the tail blood of small rats (less than 100 g body weight). In large rats (160–225 g body weight) there was no significant difference in the haemoglobin values of blood taken from the tail or from the heart. When two consecutive samples of heart blood were taken from small and large rats, the second sample from the small animals had a lower haemoglobin concentration than the first. These variations can cause difficulty in interpreting haemoglobin results from laboratory rats, and indicate the importance of stating exactly what techniques were used when reporting haematological findings.