bluuebunny/crossref_metadata_2025 huggingface dataset:
Erythrocyte Abnormality Induced, by Protein Malnutrition
Authors: Lanzkowsky P. , McKenzie D. , Katz S. , Hoffenberg R. , R. Friedman  , Black E.
Published: March 2008

Red cell survival studies using 51 Cr‐labelled erythrocytes were carried out on 14 subjects with protein malnutrition (12 kwashiorkor and two marasmus). The T½ varied from 3 to 20 days with a mean of 12.4 days. There was significant accumulation of radioactivity demonstrable on scanning over the liver and spleen in three kwashiorkor patients.

Erythrocytes of three kwashiorkor patients showed shortened T½ both when auto‐transfused and when injected into three normal controls. The T½ of erythrocytes from two normal donors injected into four subjects with kwashiorkor was also considerably reduced.

After protein repletion, auto‐transfusion in nine cases showed a T½ which varied from 20 to 29 days with a mean of 23.7 days.

This investigation has shown considerably reduced erythrocyte survival in patients with protein malnutrition (kwashiorkor and marasmus); this shortened survival time appears to be due to both corpuscular and extra‐corpuscular factors. Following protein feeding considerable improvement in the erythrocyte survival took place. Since improvement in erythrocyte survival occurred on a low iron‐containing protein diet without haematinics or vitamin supplements it is considered that protein depletion is principally responsible for this shortened survival.
The Origin of the Elevated Serum Lactate Dehydrogenase in Megaloblastic Anaemia
Authors: Emerson Pauline M. , Withycome Wendy A. , Wilkinson J. H.
Published: March 2008

The high serum lactate dehydrogenase activity found in megaloblastosis is almost entirely due to major increases in the anodic isoenzymes. Since the cathodic fractions predominate in the liver, gastric mucosa, lymphatic tissue and peripheral leucocytes these tissues are unlikely to be responsible for the raised serum activity. Of the tissues rich in anodic isoenzymes, the heart and kidney are not considered to be important contributors since, in the case of the former, there is no associated increase in aspartate transaminase activity, and the latter does not undergo major tissue damage in megaloblastosis. The amount of peripheral haemolysis which occurs in pernicious anaemia is not considered to account for more than a small part of the increased enzyme activity in the serum. The lactate dehydrogenase of megaloblastic bone marrow consists principally of anodic isoenzymes whereas that of normal marrow is largely cathodic, and the very high rate of destruction of immature and abnormal erythroid precursors in the bone marrow of patients with megaloblastosis is considered to be the most likely source of the raised serum enzyme activity.
Absorption of Unaltered Folic Acid, from the Gastro‐intestinal Tract in Man
Authors: Whitehead V. M. , Cooper B. A.
Published: March 2008

Hepatic portal and systemic plasma folate levels were determined in human subjects during umbilical‐vein catheterization after oral administration of folic acid. Hepatic‐vein blood was obtained during right heart catheterization. Serial folate measurements with L. casei and S. faecalis and TEAE‐cellulose chromatography revealed that folic acid is rapidly absorbed into the portal blood without undergoing metabolic conversion. A delay in rise in folate levels in systemic and hepatic‐vein blood, together with the finding of large amounts of folic acid and methylfolate in blood subsequently leaving the liver, indicates that this organ is the major site of folic‐acid metabolism.
Antibody to Intrinsic‐Factor‐Vitamin‐B12 Complex in Pernicious Anaemia
Authors: Cooper B. A. , Yates T.
Published: March 2008

Serum from some patients with pernicious anaemia contains antibody activity to human intrinsic factor‐57CoB12 complex (IF‐57CoB12) which can be detected by co‐precipitation of IF‐57CoB12) with the globulin fraction precipitated with 45 per cent ethanol. The characteristics of this antigen‐antibody reaction include some dissociation of antigen from antibody during precipitation, and ready cross‐reaction of antibody with IF to which vitamin B12 is not bound. The IF‐B12 antigen also cross‐reacts with anti‐intrinsic‐factor antibody, as measured by the charcoal adsorption technique. This co‐precipitation technique may be to determine whether small quantities of B12‐binding material have the immunological characteristics of intrinsic factor. Although the anti‐IF antibody present in the blood of many patients with pernicious anaemia may be responsible for this anti‐IF‐B12 antibody activity, it is possible that a separate antibody system exists which is directed against IF‐B12.
Quinine‐Induced Haemolysis: Mechanism of Action
Authors: Bennett J. M. , Desforges Jane F.
Published: March 2008

Quinine hydrochloride was found to produce striking haemolysis of whole blood in vitro, preceded by rounding of red cells, K+ leakage, and decreased resistance to hypotonic saline solutions. Evidence is presented to indicate that quinine does not interfere with the pentose phosphate pathway. Its primary damage may be on membranes and is possibly‐related to oxidation of sulphhydryl groups.
Patterns of Red Cell Destruction in Sickle‐Cell Anaemia
Authors: Hathorn M.
Published: March 2008

Nine patients with sickle‐cell anaemia were studied by body surface counting over the spleen and liver following the injection of 51Cr‐labelled red cells. In two of the patients without palpable spleens there was no excess accumulation of radioactivity over the spleen, and the spleen/liver ratio declined with time. In the remaining seven patients, all with splenomegaly, there was decreased red cell survival, an excess accumulation of radioactivity over the spleen, and an increase in the spleen/liver ratio with time, indicative of sequestration of red cells by the spleen. The significance of these findings is discussed.
Electron‐Microscopy of Türk Cells
Authors: Sprigs A. I. , Jerrome D. W.
Published: March 2008

Electron‐micrographs have been made from mononuclear‐cell concentrates of peripheral blood from two patients in whom there were numerous circulating Turk cells. There appears to be a series from immature forms with the morphological characters of ‘blast cells’ up to cells with the fully developed cytoplasmic characters of plasma cells.
Nucleolar Staining in the Differentiation of Acute Leukaemias
Authors: Salsbury A. J.
Published: March 2008

The results of an investigation into 45 cases of acute leukaemia, using the Chromotrope 2R nucleolar staining techniques of Gillis and Baikie have been reported. Although no clear distinction can be drawn between the various types of ‘blast cells’, lymphoblast tend to have spherical nucleoli, less than two to a nucleus and deeply‐staining, whereas myeloblast tend to possess two or more irregular, faintly‐staining nucleoli per cell. Nucleolar staining may be of value in the classification of some cases of acute leukaemia.
Incidence of Iron Deficiency, with and without Anaemia, in Women in General Practice
Authors: McFarlane D. B. , Pinkerton P. H. , Dagg J. H. , Goldberg A.
Published: March 2008

The incidence of iron deficiency anaemia in 500 women in an urban general practice was found to be 8.2 per cent, 9.7 per cent in 402 ‘patients’ and 2 per cent in 98 symptomless volunteers (‘subjects’). Iron deficiency anaemia was diagnosed when the haemoglobin was less than 12 g. per 100 ml. and the saturation of the total iron binding capacity of the serum was less than 16 per cent.

Women who had a haemoglobin of more than 12g. per 100 ml. but who had a saturation of the total iron binding capacity of less than 16 per cent, were considered to be ‘iron deficient without anaemia’. This state was found in 22.2 per cent of ‘patients’ and 16.3 per cent of ‘subjects’.

There was no decrease in the incidence of iron deficiency following the menopause; indeed, iron deficiency with and without anaemia was slightly more common over the age of 40 years. While a higher incidence was seen in widows than in married or single women, this difference was not significant, nor were the differences in the social classes or ABO, blood groups.
Sequence of Events Terminating in Death of Leucocytes
Authors: Aune Janet M. , Gantner G. E. , Wade N. J.
Published: March 2008

Cellular damage in human granulocytes was evident by light microscopy after 24 hours of 30° C. incubation in unfortified whole blood. Injury was indicated by the cell's inability to accommodate neutral red and the simultaneous loss of motility. Cellular death was delimited to this loss of physiological integrity.

Biochemical changes which occurred intracellularly during incubation were correlated with changes in the surrounding milieu: plasma glucose diminished first, and after this was depleted there was histochemical evidence of decreased cytoplasmic glycogen. It appears by analogy, therefore, that after the glucose was utilized, intracellular glycogen may have been used for energy metabolism enabling the cell to function an additional 10–15 hours. When nutrient deficiency produced structural disintegration, the cell was unable to maintain itself and death followed.
Biological Half‐Life of Transfused Antihaemophilic Globulin (Factor VIII) In Normal Man
Authors: Pool Judith G. , Cohen Theodore , Creger William P.
Published: March 2008

The biological half‐life of anti‐haemophilic globulin (Factor VIII) was determined in two normal subjects. Using plasmapheresis, approximately 25 bags of plasma were collected from each over a 9‐week period. From these plasma donations, cryoprecipitates were prepared and stored in the freezer. At the time of the study their pre‐infusion Factor‐VIII levels were carefully determined and then the pooled solutions of the cryoprecipitates rapidly administered and the post‐infusion Factor‐VIII levels determined serially. Although fluctuations in level interfered with the establishment of a smooth curve, the approximate half‐life time was 2+ hours for each subject. It was concluded that the biological half‐life for Factor VIII in the normal is no longer than, and possibly shorter than, that for the haemophilic subject and that this observation supports the hypothesis that haemophilia is a disease of inadequate synthesis of Factor VIII rather than of accelerated destruction.
Hereditary Elliptocytosis in Iceland
Authors: Jensson Ó. , Jonasson Th. , ÓLafsson Ó.
Published: March 2008

An Icelandic family with 50 elliptocytic individuals is surveyed. Pedigree studies indicate strongly that affected members of the family are descendants of a common ancestor. The hereditary pattern is typical for a dominant, autosomal gene with full penetrance. A high incidence (over 57 per cent) of signs and/or symptoms of haemolysis is found among the affected at one time or another. No haptoglobin was detected in 80 per cent of affected individuals investigated. The age distribution of the affected at the time of diagnosis shows an increased incidence of anaemia with increasing age. In three affected individuals splenectomy has been performed with satisfactory results.

The variation in the grades of haemolysis and the high incidence of haemolysis found in the affected family members are discussed.
Lysis of P.N.H. Cells in Solutions of Low Ionic Strength
Authors: Stratton F. , Evans D. I. K.
Published: March 2008

A test to detect P.N.H. red cells when exposed to fresh serum in a sucrose‐veronal‐albumin buffer solution of low ionic strength, pH 7.6, is described.

The serological findings suggest that the basis of the test is another example of the peculiar sensitivity of P.N.H. cells to complement in the presence of antibody.
Intravascular Haemolysis with Experimentally Produced Vascular Thrombi
Authors: Brain M. C. , Esterly J. R. , Beck E. A.
Published: March 2008

Studies are presented on the haemoglobinaemia observed during intravascular coagulation in rabbits due to thrombin infusion or endotoxin injection.

The haemoglobinaemia was unrelated to the type or amount of thrombin, but was closely correlated to the degree and extent of fibrin thrombi in the renal glomeruli and in the small vessels of other organs, an effect potentiated by thorotrast.

The haemoglobinaemia was not dependent on the presence of the spleen or the kidneys, or on circulating granulocytes, but could be prevented by heparin.

The haemoglobinaemia was associated with the appearance of fragmented red cells in the circulation.

It is suggested that the haemoglobinaemia is due to intravascular destruction of red cells at the site of fibrin thrombi, and that changes in the red cell may also enhance thrombosis.
The Effect of Iron Stores on Ferrokinetics in Polycythaemia
Authors: Ellis L. D. , Westerman M. P. , Balcerzak S. P.
Published: March 2008

The ferrokinetic data of patients with primary polycythaemia are those of patients with depleted iron stores. Differences in iron kinetics between polycythaemia vera and secondary polycythaemia are related to the variation in the quantity of iron stores and do not appear to be inherent to the type of polycythaemia. If ferrokinetic studies are to be used to evaluate or classify polycythaemia, storage iron must be assessed.
Experiments on the Nature of the Prothrombin‐Converting Principle: Alteration of Proaccelerin Thrombin
Authors: Prentice C. R. M. , Ratnoff O. D. , Breckenridge R. T.
Published: March 2008

An incubation mixture of activated Stuart factor, calcium, phospholipid and proaccelerin caused the generation of thrombin from prothrombin. The activity of this prothrombin‐ converting principle was measured by the rate at which it converted prothrombin to thrombin. In the absence of thrombin in the incubation mixture, a lag phase, following addition of the prothrombin‐converting principle to prothrombin, was observed before thrombin formation occurred. But when a trace of thrombin was added to the incubation mixture, it converted the principle into an active form, causing the immediate formation of thrombin from prothrombin without any delay. It was demonstrated that thrombin had this action upon the prothrombin‐converting principle by changing proaccelerin into a more active form.

Thrombin‐treated proaccelerin would not convert prothrombin to thrombin in the absence of activated Stuart factor, indicating that it is not, by itself, the prothrombin‐converting principle.

By purification of the thrombin preparation, and the use of hirudin, it was shown that the action of thrombin on proaccelerin was due to thrombin itself and not to activated Stuart factor or other contaminating substances in the thrombin preparation.
Desferrioxamine Chelatable Iron in Haemolytic, Megaloblastic and Sideroblastic Anaemias*
Authors: Karabus C. D. , Fielding J.
Published: March 2008

The chelation of body iron by desferrioxamine methanesulphonate in patients with haemolytic anaemias of varying types, in megaloblastic and in sideroblastic anaemias was measured by the differential ferrioxamine test. Thirty‐five out of 44 patients studied had chelation values above the normal range, sometimes exceeding those found in untreated haemochromatosis.

In the haemolytic anaemias, the amount of chelation increased with the severity of the anaemia. In the megaloblastic anaemias, specific therapy reduced the amount of iron chelated by desferrioxamine at the same time as normal erythropoiesis was re‐established.

Concepts of labile iron and metabolically active iron are compared with desferrioxamine chelatable iron. These findings suggest that in addition to storage iron (ferritin‐haemosiderin) chelated with difficulty, there is a compartment of readily chelatable iron derived from haem catabolism, possibly sited in reticulo‐endothelium. A model of intracellular iron transport in reticulo‐endothelial cells is proposed which provides a primary pathway of metabolically active, highly chelatable iron derived from haemoglobin catabolism, and a secondary pathway to intracellular ferritin.
VII. CHANGES IN LYMPHOCYTES AND TRANSITIONAL CELLS IN THE BONE MARROW DURING PROLONGED REBOUND
Authors: Jones Hilary B. , Jones J. J. , Yoffey J. M.
Published: March 2008

The bone marrow has been studied by a quantitative technique in 48 guinea‐pigs from the 8th to 12th days of rebound following 7 days of hypoxia at a simulated altitude of 17,000 feet. On the 8th and 9th days of rebound there is a highly significant increase in the small lymphocytes, which form nearly 70 per cent of all the nucleated cells of the marrow. This increase is associated with a fall in the transitional lymphocytes and also of the myeloid cells. The significance of these changes is discussed.
VIII. EFFECT OF HYPOXIA AND POST‐HYPOXIC POLYCYTHAEMIA (REBOUND) ON MOUSE MARROW AND SPLEEN
Authors: Turner M. S. , Hurst J. M. , Yoffey J. M.
Published: March 2008

Quantitative marrow changes,59Fe incorporation into erythrocytes and spleen weight variations have been studied in mice during primary hypoxia and rebound. The pattern of the mouse response to hypoxia is similar to that already described in the guinea‐pig. The possible involvement of the lymphocyte in erythropoiesis whether as stem cell or otherwise is suggested by the fact that its accumulation in the marrow seems to be inversely related to erythropoietic activity. The effect of hypoxia on the stem cell compartment is discussed.
Leucocyte Folate in Vitamin B12 and Folate Deficiency and in Leukaemia
Authors: Hoffbrand A. V. , Newcombe Beverley F. A.
Published: March 2008

Leucocyte folate concentrations were measured in 24 normal subjects, in 32 patients with subnormal serum folate concentrations and normal serum B12 concentrations associated with chronic gastro‐intestinal disease, in seven patients with leukaemia, and in 10 patients with untreated pernicious anaemia.

In the normal subjects, the leucocyte folate levels ranged from 60 to 123 ng./ml. of packed leucocytes. Among the patients with subnormal serum folate concentrations, leucocyte folate concentrations were normal in seven or eight patients with entirely normoblastic haemopoiesis, but were subnormal in all eight patients whose marrows showed normoblastic erythropoiesis and giant metamyelocytes, in all eight patients with obvious megaloblastic changes, and in all eight patients with overt megaloblastic anaemia due to folate deficiency.

Leucocyte folate was raised in six of the seven patients with leukaemia including patients with acute and chronic myeloid leukaemia, myelomonocytic leukaemia and chronic lymphatic leukaemia.

Of the 10 patients with untreated pernicious anaemia, three had raised, three had normal, and four subnormal leucocyte folate. The changes in leucocyte folate produced by B12 therapy in four of the pernicious anaemia patients are described.
Erythroid Aplasia in Riboflavin‐Deficient Baboons and its Relation to Marasmus and Kwashiorkor
Authors: Kondi Athena , Foy H. , Mbaya Vertistine
Published: March 2008

An erythroid hypoplasia characterized by falls in red cell precursors, haemoglobin, packed cell volume, reticulocytes and sometimes platelets, resembling that which occurs in marasmus and kwashiorkor, has been produced experimentally in baboons on a synthetic riboflavin‐deficient diet. The red cell uptake of59Fe on the 8th and 12th days was 40 per cent lower in the riboflavin‐deprived animals and thus agreed with the low marrow activity estimated cytologically. The haematological abnormalities were accompanied by gross skin changes, falls in serum folate, and sometimes intramuscular and intestinal haemorrhages. Striking macroscopic and histological abnormalities were also present in the adrenals. All the abnormalities disappeared when riboflavin was given, and re‐appeared when it was again omitted from the diet. When prednisone was given to the deprived animals instead of riboflavin, only the erythroid hypoplasia disappeared. Since the diet was adequate in all respects and contained 20 per cent of its kilocalories in the form of animal protein, the abnormalities cannot have been due to protein deficiency. The pair‐fed controls on a similar diet but with added riboflavin developed no abnormalities. It is suggested that as riboflavin is an important co‐enzyme in many vital metabolic processes, its absence may affect marrow activity directly or by disturbing corticosteroid metabolism, as well as being associated with serum protein changes.
Complications and. Treatment of Acquired Aplastic Anaemia
Authors: Vincent P. C. , Gruchy G. C. de
Published: March 2008

The clinical and haematological findings in 43 cases of aplastic anaemia are reviewed. Approximately two‐thirds of the cases were considered to be secondary to toxic agents, the commonest of which were chloramphenicol and phenylbutazone, and one‐third were idiopathic. Severe neutropenia and thrombocytopenia were a feature of the series, a neutrophil count of less than 500/cu.mm. and a platelet count of less than 20,000/cu.mm. being found initially in over one‐half of cases. There was an unexplained and marked elevation of the ESR in over 90 per cent of cases. Fifty‐two episodes of infection occurred in 29 patients (67 per cent); 36 of these episodes were serious. Infection was more frequent in young patients and serious infection was more likely in the presence of severe neutropenia. The occurrence of infection, especially serious infection, was usually followed by a fall in neutrophil and platelet counts, and frequently by the onset of serious bleeding. Bleeding phenomena occurred at some stage in all but one patient and in two‐thirds of cases the bleeding was serious. Thrombocytopenia was marked in patients with serious bleeding but equally low platelet counts were found in patients in whom bleeding was not serious. The onset of serious bleeding was more likely in the presence of infection.

Administration of corticosteroids or corticotrophin either with or without androgens was followed by a haematological response in about two‐thirds of cases, but in only one‐third was the response sustained; in the remainder it was transient. In those with a sustained response, the haemoglobin and neutrophil values gradually increased and ultimately returned to normal; however, the platelet count returned to normal in less than one‐half of these.

The overall mortality rate was 63 per cent, bleeding and infection being the commonest causes of death. The mortality was higher in the idiopathic cases (86 per cent) than in the secondary cases (52 per cent); however, the period of survival in fatal secondary cases was shorter than that in fatal idiopathic cases. The prognosis appeared to be better in patients with secondary aplasia, in patients with an initial haemoglobin value greater than 8 g. per 100 ml., and in patients who remained free of serious bleeding. The outcome showed no relation to sex, age, the initial neutrophil and platelet counts or the cellularity of the bone marrow on admission. Seven of the 16 survivors are considered cured, eight are well but are still thrombo‐cytopenic, and one has developed paroxysmal nocturnal haemoglobinuria 8 years after diagnosis and 6 years after a complete haematological remission. Treatment with corticosteroids is still necessary to control bleeding in three of the eight survivors with thrombocytopenia.
X‐Linked Hypochromic Anaemia of Mice
Authors: Bannerman R. M. , Pinkerton P. H.
Published: March 2008

An X‐linked recessive mutant gene (symbol sla) in the mouse causes hypochromic anaemia in hemizygous males and homozygous females; heterozygous carrier females show only slight changes. A detailed assessment of the anaemia is presented here. The red cells show a wide variety of morphological changes, including target cell formation, and the MCV is strikingly reduced. The anaemia and morphological changes tend to regress with increasing age. The anaemia also responds to parenteral iron‐dextran treatment, but not to pyridoxine and other agents.

These findings and preliminary results of other investigations suggest that the underlying metabolic disturbance is likely to involve some step in the supply of iron to the erythron. It thus appears that in the mouse an X‐linked locus plays a role in iron metabolism, and this mutant provides an opportunity further to elucidate mechanisms of iron transfer.
Inhibitor of Platelet Aggregation Present in Saliva of the Vampire Bat Desmodus rotundus
Authors: Hawkey Christine
Published: March 2008

A substance capable of inhibiting ADP‐induced and thrombin‐induced aggregation of human platelets in vitro has been found in saliva of D. rotundus. This substance does not act on ADP directly but probably exerts its effect on the platelet ADP‐binding sites or on the plasma co‐factor involved in this reaction. Partial separation of the aggregation inhibitor from other active substances in the saliva has been carried out using G‐200 Sephadcx.
The Excretion of Methylmalonic Acid and Succinic Acid in Vitamin B12 and Folate Deficiency
Authors: Brozović M. , Hoffbrand A. V. , Dimitriadou A. , Mollin D. L.
Published: March 2008

The excretion of methylmalonic acid (MMA) and of succinic acid was measured in 18 control subjects and in 58 patients with vitamin B12 and/or folate deficiency.

The 18 control subjects excreted from 0.0 to 3·5 mg. MMA in 24 hours. MMA excretion was raised in 27 of 41 patients (Group I) with conditions associated primarily with B12 deficiency. These 27 patients included 15 patients with Addisonian pernicious anaemia, two patients following total gastrectomy, two patients with anatomical lesions of the small intestine and eight patients following partial gastrectomy, whereas MMA excretion was normal in four patients with atrophic gastritis and in a further 10 patients following partial gastrectomy.

In Group I, MMA excretion was raised in all but one of the patients with serum B12 levels less than 100 pg./ml. due to uncomplicated B12 deficiency, but was invariably normal in patients with borderline serum B12 levels (from 100 to 160 pg./ml.). In the patients with serum B12 levels less than 100 pg./ml., with associated iron and/or folate deficiency, the excretion of MMA tended to be lower than in patients with uncomplicated B12 deficiency, and was often normal.

MMA excretion was slightly raised in one of 17 patients with megaloblastic anaemia, primarily due to folate deficiency (Group II), although six of them had serum B12 levels less than 100 pg./ml. The patient with a raised MMA excretion needed B12 therapy for a full haematological remission.

The 18 control subjects excreted from 2.0 to 12.5 mg. succinic acid in 24 hours. Succinic acid excretion was subnormal in nine and raised in five patients in Group I. These 14 patients all had serum B12 levels less than 100 pg./ml.

None of the Group II patients excreted subnormal amounts of succinic acid but three, including two patients with serum B12 levels less than 100 pg./ml., excreted raised amounts of succinic acid.
Epitope recognition patterns of thyroid peroxidase autoantibodies in healthy individuals and patients with Hashimoto's thyroiditis*
Authors: Nielsen Claus H. , Brix Thomas H. , Gardas Andrzej , Banga J. Paul , Hegedüs Laszlo
Published: March 2008

Objective  Thyroid peroxidase antibodies (TPOAb) are markers of autoimmune thyroid disease (AITD), including Hashimoto's thyroiditis (HT), but naturally occurring TPOAb are also detectable in healthy, euthyroid individuals. In AITD, circulating TPOAb react mainly with two immunodominant regions (IDR), IDR‐A and IDR‐B. The present study was undertaken in order to compare the epitope recognition pattern of TPOAb in HT patients and healthy subjects.

Design  Sera from 21 out of 98 healthy controls were selected on the basis of high TPOAb values, required for determination of TPOAb recognition pattern; as were sera from 92 HT patients.

Measurements  Measurement of IDR‐reactivity was possible in 90 patients and 12 controls. IDR‐A‐, IDR‐B‐ and non‐IDR‐A/non‐IDR‐B‐Ab constituted 24 ± 11%, 50 ± 15% and 26 ± 12%, respectively, in the patients. The distribution in the controls was distinctly different, only 12 ± 13% being directed against IDR‐A (P < 0·002) and 66 ± 22% against IDR‐B (P < 0·002). Half of the healthy individuals, vs. none of the HT patients, lacked IDR‐A reactivity completely (P < 0·0001). In HT patients, IDR‐B‐Ab proportions increased slightly with increasing TPOAb levels (P < 0·05), while IDR‐B‐Ab of the controls showed a strong opposite trend (P < 0·0001). Accordingly, the proportion of non‐A/non‐B‐Ab correlated with TPOAb levels in the healthy controls (P < 0·008), and an inverse correlation was seen in HT patients (P < 0·02).

Conclusion  The data suggest that TPOAb do not differ only in quantity between HT patients and healthy individuals, but may also follow distinct qualitative patterns. Larger studies are required to confirm this, and to determine whether the propensity to produce antibodies to certain TPO epitopes, for example, IDR‐A, is of pathogenic relevance.
Increased serum visfatin in patients with metabolic syndrome and carotid atherosclerosis
Authors: Zhong Ming , Tan Hong‐wei , Gong Hui‐ping , Wang Shu‐fang , Zhang Yun , Zhang Wei
Published: March 2008

Objective  Visfatin is a newly identified adipocytokine and recent studies indicated that visfatin may have potential proinflammatory effect. However, its pathophysiological role in the metabolic syndrome (MetS) is not fully understood. In this study we investigated whether serum visfatin levels is altered in patients with the MetS, and compared the levels of visfatin between patients with and without carotid plaques.

Design and method  A total of 139 patients with MetS and 105 controls were included. The patients were further divided into two groups: 40 with carotid plaques and 99 without carotid plaques. Serum visfatin was measured by using enzyme immunoassay method and carotid intimal‐media thickness (IMT) was measured by ultrasound in all subjects.

Results  Serum visfatin was elevated in both MetS patients with and without carotid plaques compared to controls (log visfatin: 1·14 ± 0·14 vs. 0·99 ± 0·17 ng/ml vs. 0·93 ± 0·23 ng/ml, P < 0·001 and P < 0·05 vs. control group, respectively), and in patients with carotid plaques more than in patients without carotid plaques (P < 0·001). Multiple stepwise regression analysis revealed that only LDL‐cholesterol correlated with visfatin, and visfatin independently correlated with max IMT in the patients with MetS. A log visfatin > 1·08 ng/ml had 70% sensitivity and 67% specificity for detecting patients with carotid plaques.

Conclusions/interpretation  Our results showed that serum visfatin was increased in patients with MetS, especially in those with carotid plaques. Visfatin may be an inflammatory marker of MetS.
Contribution to the Pathogenesis of Tumour Hypoglycaemia
Authors: Frerichs H. , Willms B. , Kasper H. , Creutzfeldt C. , Creutzfeldt W.
Published: March 2008

Abstract In a patient with severe hypoglycaemia associated with an intrahepatic fibrosarcoma, hyperinsulinism could be excluded, since normal serum insulin and insulinlike activity (ILA) levels were measured in the fasting state and during glucose, glucagon, and tolbutamide tolerance tests. Treatment with methylprednisolone led to an improvement of the clinical condition of the patient. Diazoxide treatment was ineffective. Blood glucose levels were higher during corticoid therapy, but total glucose assimilation remained unchanged. Studies of the metabolism of [1‐14C] glucose before and during treatment with prednisolone showed that an inhibition of hepatic glycogenolysis was not significant for the pathogenesis of the hypoglycaemia. The differences of glucose and blood lactate after glucose i. v. before and during prednisolone suggested, however, that gluconeogenesis was increased as a result of corticoid therapy. Measurements of hepatic enzyme activities also favoured this hypothesis: activities of FDP'ase and G‐6‐P'ase were low before treatment and increased by a factor of 1.5 and 5 respectively during treatment, indicating a stimulation of the gluconeogenetic processes in the liver. It is concluded that the combination of tumoral glucose overutilization with hepatic glucose underproduction due to impaired gluconeogenesis was the pathogenetic mechanism responsible for the hypoglycaemia of this patient. Electron microscopic studies of the tumour cells revealed abundant mitochondria and a highly active ergastoplasm. In addition, secretory granules were found in the cytoplasm and some even in the mitochondria.
Effect of Experimental Hypertriglyceridaemia on Tissue and Serum Lipoprotein Lipase Activity
Authors: Shafrir Eleazar , Biale Yigal
Published: March 2008

Abstract Hypertriglyceridaemia was produced in rats by the intravenous infusion of Intralipid emulsion or of very low density (d < 1.006) rabbit or human lipoproteins (VLDL). Lipoprotein lipase activity was assayed, in tissues removed at the end of infusion, on serum‐activated mono‐ and triolein emulsions at pH 8.6. Hypertriglyceridaemia resulted in a marked decrease in epididymal adipose tissue lipoprotein lipase activity and in an increase in heart enzyme activity. These changes were evident with both mono‐ and triolein substrates. The effects on adipose tissue enzyme activity seemed roughly dependent on the triglyceride (TG) level and, relative to TG elevation, were most pronounced in the case of VLDL infusion. Serum lipoprotein lipase activity, measured in the absence of heparin, was considerably increased suggesting that the TG‐rich material “leached” the adipose tissue enzyme into the circulation. Leaching of lipoprotein lipase from adipose tissue by Intralipid emulsion or VLDL was also demonstrated in an in vitro system devoid of heparin. Contact with the TG‐poor, 1.006 < d < 1.063, lipoprotein induced only a small loss in adipose tissue lipoprotein lipase activity, either in vitro or in vivo.

Intracellular lipolytic activity toward mono‐ and triolein, measured in adipose tissue and heart homogenates at pH 7.2 in the absence of serum, was not significantly affected by TG elevation. Thus, the observed changes in lipoprotein lipase activity seem unrelated to the intracellular lipolytic activity.

It is suggested that the low adipose tissue lipoprotein lipase activity and the retarded TG removal observed in certain hypertriglyceridaemic conditions may be secondary to the increased supply of TG‐rich lipoproteins.
Precipitation by Neomycin Compounds of Fatty Acid and Cholesterol from Mixed Micellar Solutions
Authors: Thompson G. R. , MacMahon M. , Claes P.
Published: March 2008

Abstract The effect of the polybasic antibiotic neomycin on micellar solutions of labelled lipids and bile salts was studied both in vitro and in vivo. The addition of neomycin sulphate to simple micellar solutions of bile salts in vitro raised the pH of precipitation of the glycine conjugates and induced precipitation of the taurine conjugates of dihydroxy bile acids, but had no effect on the corresponding trihydroxy compounds. Addition of neomycin to mixed micellar solutions caused precipitation of most of the fatty acid, monglyceride and cholesterol, but a lesser proportion of bile salt. Precipitation of mixed micellar solutions by neomycin was conditional on the presence of fatty acid and progressively lessened above pH 6.5. Two basic derivatives, Compound R. I. T. 1,291 and N‐methyl neomycin, also precipitated fatty acid, in contrast to the neutral compound X‐acetyl neomycin. In vivo the uptake of labelled oleic acid and cholesterol from mixed micelles, one hour after intraduodenal administration to rats, was markedly decreased by the simultaneous administration of neomycin sulphate 10 to 50 mg. Similarly, in rats with cannulated intestinal lymphatics and bile ducts, the lymphatic transport of labelled fatty acid and cholesterol was also inhibited by neomycin, although this had no effect on the absorption and biliary re‐excretion of labelled taurocholate and taurodeoxycholate. These results suggest that basic neomycin compounds precipitate mixed micellar solutions primarily by their ionic interaction with fatty acids, and thus can interfere with the absorption of both fat and cholesterol.
Nonsuppressible Insulin‐Like Activity (NSILA) of Human Serum*
Authors: Oelz O. , Jakob A. , Froesch E. R.
Published: March 2008

Abstract 10 mU of NSILA‐S, as determined by the fat pad assay, lowered blood glucose and free fatty acids of adrenalectomized rate for a much longer period than 10 mU of crystalline insulin. NSILA‐S was not measurably inactivated by the liver during a 2 h cyclical perfusion, whereas insulin rapidly lost activity with a half‐life of 42 min. 6 mU of NSILA‐S injected intravenously stimulated the incorporation of [6‐14C] glucose into the diaphragm of streptozotocin‐diabetic rats to a much greater extent than 6 mU of insulin, whereas their effects on the incorporation of carbon 14 into the fat pad were equal.

When injected intraperitoneally in maximal doses to normal rats both agents stimulated the incorporation of [U‐14C] glucose into adipose tissue and diaphragm to the same extent. There was no potentiation of either agent by the other on adipose tissue in vitro, indicating that they affect the same transport site of the cell membrane. Insulin and NSILA‐S influenced the metabolism of adipose tissue of fasted‐refed rats in the same manner.

It is concluded that i.v. injected NSILA‐S is more effective in vivo than comparable doses of insulin because it is not inactivated by the liver. Furthermore, it seems to have a particular affinity to receptors of the muscle cell membrane. This may be an additional factor in protecting it from inactivation by other tissues.
Studies on the Haemodilution Anaemia of Splenomegaly
Authors: Blendis Laurence M. , Ramboer Carlos , Williams Roger
Published: March 2008

Abstract The occurrence and causes of a haemodilution anaemia have been studied in two groups of patients, one with diseases of the blood or reticulo‐endothelial system, the other with cirrhosis.

In the blood dyscrasia group 37 of 46 patients were anaemic but only 3 had a reduced red cell mass. In the remainder the plasma volume was increased to a greater extent than the red cell mass which was slightly elevated or within the normal range. A significant correlation was found between a decrease in haemoglobin concentration and an increase in plasma volume. Both the increase in plasma volume and the changes in red cell mass were related to enlargement of the spleen. Measurements carried out at splenectomy showed that an excess of red cells was held within the enlarged spleen whereas up to 30 per cent only of the excess plasma could be found there. A correlation between the plasma volume and spleen blood flow was found but both are related to spleen size and the most likely explanation for the increased plasma volume was a primary increase in vascular capacity. The different effect of posture on the plasma volume in patients before and after splenectomy would also support this hypothesis.

In contrast, 20 of the 50 cirrhotic patients were anaemic and seven of these had a reduced red cell mass. In the other 13 patients the plasma volume was increased to a greater extent than the red cell mass but even in those with a haemodilution anaemia, the haemoglobin concentration was not inversely related to the plasma volume. In seven patients the increase in plasma volume was less than that of the red cell mass and four patients were polycythaemic. There was no correlation between the changes in red cell mass and plasma volume or between either of these and the enlargement of the spleen. The presence of portal hypertension appeared to be an important factor but the increase in plasma volume was not related to the extent of the portosystemic venous collaterals.
A Study of the Cross‐Reaction between Human Chorionic and Pituitary Luteinizing Hormones (HCG and HLH)
Authors: Franchimont Paul
Published: March 2008

Abstract The cross‐reaction between HCG and HLH was studied by radioimmunological techniques using 43 anti‐HCG sera. With some of them the cross‐reaction between HCG and HLH was complete as shown by the similar inhibition of binding of labelled HCG and HLH to antibody obtained with both hormones. A few antisera failed to react identically with labelled HCG in the presence of unlabelled HLH and HCG, but with labelled HLH identical inhibition slopes were yielded by unlabelled HLH and HCG. Moreover, with one antisera labeled HLH bound poorly to antibody and unlabelled HLH produced only a slight decrease in the percentage of labelled HCG bound to antibody. These experiments indicate that the cross‐reaction between HCG and HLH is incomplete and that there are immonologically active sites which are specific for HCG and which are not possessed by HLH.
Urinary Excretion of Catecholamines and their Main Metabolites after Myocardial Infarction; Relationship to the Clinical Syndrome
Authors: Jéquier Eric , Perret Claude
Published: March 2008

Abstract Serial measurements of the urinary excretion of noradrenaline (NA), adrenaline (A), normetanephrine + meta‐nephrine (NMN) and vanillylmandelic acid (VMA) have been made in 18 patients with acute myocardial infarction and in 2 patients with severe and recurrent episodes of angina pectoris. The urinary excretion of these 4 compounds was significantly elevated in the patients with myocardial infarction whereas it was within the normal range in the 2 patients with angina pectoris. — NA+A / NMN+VMA ratio was calculated in the 18 patients with myocardial infarction. This ratio was significantly higher in the patients (during the first 4 days after the onset of the infarction) than in the controls. This may indicate that the rate of enzymatic inactivation of NA and A is relatively decreased after myocardial infarction.— The excretion of catecholamines and metabolites was found to be higher in patients with hypotension (systolic blood pressure < 90 mm Hg) and heart failure, than in patients without these complications. Frequent and. severe ventricular arrhythmias were observed in the 6 patients with the highest urinary excretion of catecholamines and metabolites. Among the 12 patients who had a less marked increase in excretion of these compounds, 2 had episodes of ventricular arrhythmias, 5 had supraventricular arrhythmia and 5 had no complications. — Our results suggest that in most cases of myocardial infarction, the marked release of catecholamines is accompanied by a decreased rate of inactivation of these amines. This must lead to high levels of circulating catecholamines which could be related to the development of arrhythmias.
Reticulocytes and Plasma Iron Turnover in Man*
Authors: Ganzoni Andreas M.
Published: March 2008

Abstract In anaemic human subjects with adequate marrow regeneration reticulocyte contribution to plasma iron turnover was assessed quantitatively. If peripheral cellular radioiron uptake was significant, the analysis of the incorporation curve obtained in vivo permitted a first quantitative estimate. Secondly, reticulocyte iron uptake was calculated on a single cell basis in vitro. The plasma iron turnover was then related to total reticulocyte iron uptake. The agreement between the two methods was good. In the 8 patients studied, the reticulocyte contribution to plasma iron turnover ranged from 2% to 22%. The individual iron status appeared to play a decisive role in determining the fraction of peripheral cellular uptake, indicating that at low levels of plasma iron concentration reticulocytes compete successfully for iron with erythroid cells located in the bone marrow.
The Effects of Starvation on Lipogenesis in Human Adipose Tissue
Authors: Galton D. J. , Wilson J. P. D.
Published: March 2008

Abstract 1. The effects of starvation on glyceride synthesis have been studied in biopsies of human adipose tissue. After a week's fast glyceride synthesis from glucose (8.3 and 14 mM) was reduced by about 70% in intact adipose tissue; this occurred within 5 days of starting the fast.—2. A method has been devised to follow the simultaneous incorporation of 14C‐l‐palmitate into acyl‐CoA, phospholipid and neutral lipid in homogenates of human adipose tissue. This system was sensitive to fluoride which produced an accumulation of radioactivity in phospholipid and a reduction in neutral lipid.— 3. Starvation also reduced the incorporation of 14C‐l‐palmitate into neutral lipid in a similar incubation system, but radio‐activity now accumulated in long chain acyl‐CoA. This suggests that fasting is accompanied by an inhibition of L‐glycerol 3‐phosphate acyl transferase (E.C. 2.3.1.15).—4. Oleate (600 μM), which is similar to concentrations found in homogenates of fasting adipose tissue, was found to inhibit the activity of acyl transferase by about 80%. The possibility was therefore considered that the reduction of lipogenesis during fasting is mediated by free fatty acid inhibiting the acyl transferase.
Influence of Bile Acids on the Synthesis of Biliary Phospholipids in Man
Authors: Nilsson Sv. , Scherstén T.
Published: March 2008

Abstract: The effect of interrupting the enterohepatic circulation (EHC) of bile acids on the synthesis of biliary lecithin in the human liver was studied. —‐ Carbon‐14 palmitic acid was given intravenously to eight patients undergoing biliary drainage after cholecystectomy for uncomplicated gallstones, and the incorporation of label into biliary lecithin was determined. During intact EHC of bile acids the specific activity of biliary lecithin, after an initial peak, decreased progressively between 2–24 h after administration of label. During interrupted EHC the specific activity 5–6 h after the administration of label became stable at a plateau which persisted for at least 24 h. Duodenal feeding of bile acids during this period of stabilization resulted in a rapid and marked decrease in this activity. —‐ It is concluded that the bile acids in the EHC are a determining factor for the synthesis rate of biliary lecithin in the human liver. However, the mechanism for this effect on the lecithin synthesis cannot be clarified by this study.
Study of the Permeability of the Isolated Dog Mesentery*
Authors: Nagel Wolfram , Kuschinsky Wolfgang
Published: March 2008

Abstract Permeability coefficients for water‐soluble substances of different molecular weights and hydraulic conductivities were measured using the isolated mesentery of the dog. The permeability coefficients of all investigated substances show the same relation to each other as the diffusion coefficients in free solution. From these data we conclude that these substances pass the mesentery by free diffusion in aqueous channels. The fraction of the endothelial membrane area which is free for diffusion was calculated to be 4%. No steric hindrance was observed even for the largest molecule (dextran mol. wt. 500000). From the hydraulic conductivity and the diffusion permeability for water a mean equivalent pore radius of 0.575 μ was calculated for the endothelial cells. We conclude that the limiting membrane for peritoneal dialysis is the capillary endothelium.
Inhibition of Free Fatty Acid Oxidation by Acetoacetate in Normal Dogs
Authors: Balasse E. O.
Published: March 2008

Abstract The rate of turnover and oxidation of plasma free fatty acids (FITA) was measured in 7 normal anaesthetized dogs infused at a constant rate with l‐14C‐palmitate for 5 h. After a control period, sustained hyperketonaemia was induced by infusing sodium aceto‐acetate (AA). This produced a fall in plasma FFA (33%) and in blood sugar (24%), without changes in immuno‐reactive insulin (IRI) concentrations. During the control period, the turnover rate of carbon of FFA averaged 131 μat./kg/min, 32% of which were oxidized, thus supplying 17.7% of the total CO2 production. At the end of the AA infusion, the mean turnover rate of FFA was reduced to 75μat.C/kg/min; since only 13.9 % of these were oxidized, the contribution of FFA to total CO2 production was reduced to 4.3%. In the light of previous work showing that ketone infusions also reduce the rate of turnover and oxidation of glucose in dogs, we conclude that, under appropriate experimental conditions, ketones may strongly reduce the role of FFA and glucose as sources of energy.