bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemoglobin FHouston: A Fetal Variant
Authors: SCHNEIDER ROSE G. , JONES RICHARD T. , SUZUKI KIYOSHI
Published: October 2019

A fetal hemoglobin variant, designated hemoglobin FHouston, was found in the cord blood sample of a healthy, term Negro infant. The variant, comprising about 15 per cent of the total cord blood hemoglobin, diminished concomitantly with hemoglobin F, and it was barely detectable in the blood when the infant was 4 months old. The hemolysates of the parents and two siblings resolved into the usual adult pattern, but a trace amount of a fraction similar to hemoglobin FHouston was present in the father’s hemolysates and not in the mother’s.

The ultraviolet absorption spectrum indicates that hemoglobin FHOUSTON contains γ polypeptide chains, and immunologic studies reveal the presence of both α and γ chains. In hybridization tests the alteration appears in the γ chain.

Peptide chromatograms of hemoglobin FHouston indicated the presence of α and γ chains, but failed to reveal an abnormality. Amino acid analyses suggest that there may be a substitution of an alanyl for a glutamyl residue.
Brief Report: Method A Quantitative Rebuck Technic
Authors: SOUTHAM CHESTER M. , LEVIN ARTHUR G.
Published: October 2019

A Simple technic is described by which the cells exuded from a skin abrasion can be collected as a cell suspension suitable for quantitation and for further study of the living cells. The technic is identical in principle to the quantitative modification of Rebuck’s "skin window" technic which was devised by Perillie and Finch, but the smaller flatter chamber is more easily affixed to the arm and rarely leaks and can be left in place overnight without interfering with sleep. Hence, it is more acceptable to the subjects under study and technically more satisfactory. It provides a method of obtaining normal cells and of studying the cellular reaction to various antigenic or nonantigenic stimuli.
Adverse Effect of Raised Environmental Temperature on the Expression of Hereditary Spherocytosis in Deer Mice
Authors: ANDERSON RUTH , MOTULSKY ARNO G.
Published: October 2019

Deer mice with a compensated hemolytic syndrome caused by hereditary spherocytosis were placed in a controlled temperature room at 35 C. Severe anemia, red cell fragmentation, increased osmotic fragility, occasional jaundice and hemoglobinuria were observed. The spleen enlarged and the erythropoietic bone marrow expanded. Reticulocytes fell markedly early during heat exposure, but in survivors soon increased to levels higher than those observed prior to experiment. Mortality from the severe acceleration of the preexisting hemolysis was high. Control nonspherocytic deer mice subjected to an identical temperature showed only a mild drop of hemoglobin and slight elevation of reticulocytes.

Since hereditary spherocytosis in deer mice in a temperate climate is compatible with good health, these findings provide a further illustration of interaction of a particular environmental insult with a specific genotype in the pathogenesis of hereditary disease.
Virus-Like Particles and Cytopathic Activity in Urine of Patients with Leukemia
Authors: AMES RICHARD P. , SOBOTA JOSEPH T. , REAGAN REGINALD L. , KARON MYRON
Published: October 2019

Urine pellet material of patients with leukemia was examined by electron microscopy in an effort to find more convenient sources of virus material for tissue culture and animal infectivity studies. Thirty urine specimens from 16 patients with acute leukemia, 2 patients with chronic granulocytic leukemia and 1 patient with Burkitt’s lymphoma, and 17 urine samples from 15 control patients were examined. Virus-like particles were observed in 7 of the 16 patients with acute leukemia, 1 of the 2 patients with chronic granulocytic leukemia, and 1 of the 15 controls. Although these particles showed slight morphologic differences, many were similar in ultrastructure and in density gradient characteristics to the virus particles observed in murine leukemia and to the particles seen by other workers in plasma and tissues of patients with leukemia and lymphoma.

Cytopathic effects on WI-38 fibroblasts were observed in urine from 3 patients with leukemia. These effects resembled cytomegalovirus infection, but confirmatory tests were not carried out. Whether the virus-like particles demonstrated by electron microscopy in this study are responsible for the cytopathic effects is at present uncertain. The correlation of a morphologic structure with tissue culture activity cannot be answered until suitable in vitro assay and transformation systems are developed to purify and test these particles. This study suggests that urine may serve as a convenient source for the study and development of such test systems using the electron microscope to correlate structure with biologic activity.
The Effect of Acute Inflammation on the Utilization and Distribution of Transferrin-Bound and Erythrocyte Radioiron
Authors: QUASTEL MICHAEL R. , ROSS JOSEPH F.
Published: October 2019

1. In rats with acute turpentine-induced inflammation, there was a reduced reutilization of radioiron from transfused senescent erythrocytes but a normal utilization of transferrin-bound Fe59 after a 40-hour period. There was a pronounced retention of tracer from the nonviable red cells by the livers and spleens of the inflamed animals.

2. During inflammation, the plasma iron turnover fell by about 50 per cent, while the fraction of plasma iron removed per hour was increased. However, there was no marked change in the relative distribution of transferrin-bound Fe59 to the liver, spleen and bone marrow (after perfusion). Transferrin-bound Fe59 initially appeared at an increased rate in the circulating red cell mass.

3. Following administration of ferric ammonium citrate in order to raise the plasma iron level, there was a rise in the plasma iron turnover of the inflamed rats, in contrast to the control animals. Diversion of radioiron to the liver and spleen was not markedly increased under these conditions.

4. It is concluded that the immediate fall in plasma iron turnover and hypoferremia during acute turpentine inflammation results mainly from an inhibition of the release of iron derived from senescent red cells into the plasma. An increased avidity of the liver, and of marrow red cell precursors and/or reticulocytes for plasma iron may accentuate the fall in plasma iron levels. There appeared to be no inhibition of the bone marrow capacity to turn over larger amounts of plasma iron during inflammation. These results may help in the interpretation of disturbances of iron metabolism during the acute inflammatory state.
Classification and Evolution of Patterns of Erythropoiesis in Polycythemia Vera as Studied by Iron Kinetics
Authors: POLLYCOVE M. , WINCHELL H. S. , LAWRENCE J. H. , Kusubov N.
Published: October 2019

1. Patients with polycythemia vera may be classified according to their erythropoietic pattern. Erythropoiesis is abnormally increased in all classes. Class I is characterized by normal red cell lifespan. Class II is characterized by shortened red cell lifespan; in Class IIa the shortened red cell survival is related to splenic sequestration of RBC; in Class IIb the markedly shortened red cell survival is predominantly related to intramedullary hemolysis. Class III is characterized by extramedullary erythropoiesis. Patients in Classes I and IIa are in relatively earlier phases of their disease and frequently are found to develop red cell kinetics of Class III as their disease progresses. Conversely, patients in Classes IIb and III are generally late in the course of their disease and have previous hematologic findings that suggest that they originally had the red cell kinetic patterns of Classes I and IIa.

2. As the duration of their disease increases, patients with polycythemia vera generally have a progressive shortening of red cell lifespan which is incompletely compensated by a progressive decrease in circulating red cell volume. However, total blood volume remains elevated since the plasma volume increases. These changes occur whether or not the patient receives radiation therapy. Similar changes may occur in white cell and platelet production and functional survival. It is suggested that the natural history of the disease may be characterized by progressive emergence of hematopoietic cell clones which have a selective advantage for reproduction associated with altered functional survival.

3. The results suggest the potential usefulness of iron, and occasionally of splenectomy, in selected polycythemic patients with myeloid metaplasia (Class III) and anemia, dependent upon the presence of the frequent finding of iron deficiency or the occasional finding of splenic sequestration of red cells in excess of splenic erythropoiesis.
Further Cases of Hb Q-H Disease (Hb Q-α Thalassemia)
Authors: ENG LIE-INJO LUAN , PILLAY R. P. , THURAISINGHAM V.
Published: October 2019

Case reports of four patients, all Chinese, with Hb Q-H disease—also called Hb Q-α thalassemia—are presented. Three were siblings. Symptoms of chronic hemolytic anemia with jaundice and hepatosplenomegaly were present in all four subjects. The red blood cells were microcytic. Slight hypochromia was present in three of the cases. Poikilo- and anisocytosis with target cells and small intraerythrocytic crystals were found in the blood. Starch-gel electrophoresis revealed the presence of a large amount of Hb Q, a small amount of Hb H, and a minor slow-moving hemoglobin component with a mobility as much behind Hb A2 as Hb Q was behind Hb A. A small amount of Hb "Bart’s" was probably also present. The minor slow-moving component was thought to represent Hb α2Qδ2A2 or Hb Q2. Hb A and Hb A2 were not seen except after recent blood transfusion. Study of hemoglobin polypeptide chains showed the presence of normal βA-chains and abnormal αQ-chains, without demonstrable αA-chains in the first three patients. In Patient #4 normal αA-chains were demonstrable only after recent blood transfusion. The mother of the three siblings was heterozygous for Hb A; the father had α-thalassemia trait.
Treatment of Autoimmune Hemolytic Anemia in Children with Azathioprine (Imuran)
Authors: HITZIG W. H. , MASSIMO L.
Published: October 2019

Three cases of autoimmune hemolytic anemia in infants are described. This disease is very rare in the first few months of life. One case (No. 3) was complicated with a rare hemoglobinopathy, which may have been coincidental. Corticosteroid treatment in larges doses was partially and temporarily effective in controlling the disease. Immunosuppressive therapy (azathioprine = Imuran, 2-5 mg./Kg./day) produced a complete cure in Case 1 and allowed a marked decrease in steroid doses in the other two cases. Most probably, a vicious circle of autoimmunity was broken by this drug. Failure to gain weight on steroids was more than compensated for by the clear-cut "catch-up growth" in Case 1, even though Imuran was being given. Indications regarding precautions and dosage of azathioprine are stated. The exact mode of action of these drugs is discussed in an attempt to explain the nature of immunosuppression.
Studies of Lymphocyte Kinetics in Man
Authors: PERRY SEYMOUR , IRVIN GEORGE L. , WHANG JACQUELINE
Published: October 2019

Studies of certain aspects of lymphocyte kinetics were performed in nine patients with malignancies but who were hematologically normal.

Following the administration of tritiated thymidine, well-labeled large lymphocytes appeared very promptly in thoracic duct lymph along with some lightly labeled small lymphocytes. Specific activity was higher in the thoracic duct lymph lymphocytes as compared to the peripheral blood leukocytes for at least the first 50 hours.

When male patients were transfused with thoracic duct lymphocyte obtained from female donors, lymphocytes with a female karyotype were observed as early as 10 hours in the thoracic duct lymph and as early as one hour in the peripheral blood.

The evidence presented in these studies confirms data previously obtained only in animal experiments and indicates that homologous lymphocytes may circulate as long as 9 days in appropriate recipients.
Evidence for the Origin of Plasma Cells from Adventitial Cells
Authors: HIRATA-HIBI MOTOE
Published: October 2019

Arthus reactions were induced in the dorsal skin, and the subcutaneous connective tissues from the sensitized areas were examined at various stages. The subcutaneous connective tissue was used due to its simplicity of construction and because it could be studied conveniently by both supravital and fixed methods. This combination of tissue and technic allowed both an accurate classification of various types of inflammatory cells and a close examination of their relationships to the blood vessels.

Cells transitional between adventitial cells and plasma cells were observed after antigenic stimulation. Their location on the walls of the venules and capillaries indicated that they were adventitial cells but their morphology was that of plasma cells. By supravital technic they exhibited a glassy and homogeneous cytoplasm, a circular formation of neutral red granules, and a diffuse distribution of Janus green granules; and by fixed method they exhibited a chromatin pattern similar to that of plasma cells, an increased cytoplasmic basophilia, and a nucleolus was often present. Small plasma cells appeared simultaneously around the venules and capillaries. The local origin of plasma cells would appear to explain the absence of plasmacytosis during strong tissue plasma cell reactions.

Immunofluorescence was only found in plasma cells and in transitional adventitial cells, indicating a functional similarity between the 2 cells.
Detection of Glucose-6-Phosphate Dehydrogenase Deficient Heterozygotes
Authors: STAMATOYANNOPOULOS G. , PAPAYANNOPOULOU TH. , BAKOPOULOS CHR. , MOTULSKY A. G.
Published: October 2019

Heterozygotes for the Mediterranean type of severe G-6-PD deficiency were investigated by a variety of tests.

The methemoglobin reduction test was most successful in detecting heterozygotes (about 80 per cent). Enumeration of methemoglobin containing cells on blood films (Kleihauer-Betke technic) did not improve these results. Quantitation of enzyme level was less successful (65 per cent), and determination of decolorization time by the BCB technic was least sensitive in heterozygote detection.

Methemoglobin reduction technics reflect a more indirect effect of the mutant gene than enzyme assay. The superiority of these technics in heterozygote detection is probably caused by the genetically determined presence of both normal and enzyme-deficient cells in G-6-PD deficient heterozygotes. Since methemoglobin reduction is carried out by individual cells, the population of enzyme deficient cells does not reduce methemoglobin, and therefore even a minority of deficient cells leads to abnormal test results. In contrast, enzyme assay is less successful for heterozygote detection, since measurement of enzyme level is carried out on hemolyzed red cells, where cellular mosaicism no longer exists.

An additional source of variation of enzyme levels in heterozygotes is caused by the existence of genetically determined control of normal enzyme level. Possession of a high capacity allele for G-6-PD activity may place a heterozygote in the normal range of enzyme activity.

The various tests were also applied to subjects with the mild Greek type of G-6-PD deficiency. Males with this mutation had enzyme levels varying between 12-45 per cent of the mean of normal males. Methemoglobin reduction test results were considerably less abnormal in hemizygotes with the mild type of Mediterranean deficiency than in heterozygotes with the severe deficiency. Fewer heterozygotes with the mild deficiency were detected.
An Electron Microscopic Study of Thrombin-Induced Disseminated Intravascular Coagulation
Authors: MARGARETTEN WILLIAM , CSAVOSSY ILONA , McKAY DONALD G.
Published: October 2019

Fibrin thrombi due to slow intravascular coagulation appear simultaneously in rat kidney, liver, lung, and spleen, although the kidney is the only organ to show fibrin by light microscopy. The strands of fibrin are frequently associated with aggregation and viscous metamorphosis of platelets, particularly in the lungs. Some fibrin is eliminated by the reticuloendothelial system and through damaged glomeruli, but the major mechanism of removal is intravascular dissolution. Ischemic changes secondary to thrombosis are more prominent in glomerular capillaries than in other tissues. The morphologic observations are discussed in relation to "preparation" for the generalized Shwartzman reaction.
Effects of in Vivo Hyperoxia on Erythrocytes
Authors: O’MALLEY BERT W. , MENGEL CHARLES E.
Published: October 2019

During prehemolytic exposure of mice to 100 per cent oxygen, changes in glycolytic intermediates were observed. Red cell ATP and hexosemonophosphate compounds were increased and fructose 1-6 diphosphate, triose-phosphates, ADP and TPN were decreased. These changes were not affected by splenectomy or tocopherol status of the animals.
Chromosomal Aberrations Common to Three Types of Monoclonal Gammopathies
Authors: HOUSTON ELSIE W. , RITZMANN STEPHAN E. , LEVIN WILLIAM C.
Published: October 2019

1. Chromosomal patterns in 24 patients with γG-, γA- and γM-type monoclonal gammopathies (MG) are described.

2. Significant chromosomal abnormalities were observed in all three types of monoclonal gammopathies. Abnormal chromosomes in the AB size range, or larger (MG-chromosomes), were present in five of seven patients with γM-MG, in three of three patients with γA-MG and in seven of 14 patients with γG-MG. Abnormalities in the smallest group C chromosomes (pair 12), consisting of missing chromosomes, extra chromosomes, or structural anomalies, were noted in all γM-MG patients, in two with γA-MG and in eight with γG-MG.

3. The literature dealing with chromosomal aberrations in primary macroglobulinemia (Waldenström) and myeloma has been reviewed, and the various abnormalities have been discussed.

4. These chromosomal abnormalities suggest a common denominator for the three types of monoclonal gammopathies, without implying either etiologic or pathognomonic specificity.
Conversion of Cyanocobalamin to a Physiologically Occurring Form
Authors: REIZENSTEIN PETER , Kulsdom Nicolas
Published: October 2019

Results are presented which indicate that in guinea pigs cyanocobalamin undergoes conversion to hydroxocobalamin, in vivo and in vitro, at the approximate rate of 0.1-0.4 mµg./day/Gm. of liver. In boiled liver, no conversion was found.

The radioactivity excreted in human urine the first 12 hours after a therapeutic cyanocobalamin dose, on the other, is still cyanocobalamin. It is suggested that demonstrated metabolic differences between therapeutically used cyanocobalamin and hydroxocobalamin are explained, in part, by the time needed to convert cyanocobalamin to hydroxocobalamin.
Separation of Vitamin B12-Binding Proteins of Serum, Gastric Juice and Saliva by Rapid DEAE Cellulose Chromatography
Authors: RETIEF FRANCOIS P. , GOTTLIEB CHESTER W. , KOCHWA SHAUL , PRATT PETER W. , HERBERT VICTOR
Published: October 2019

A method of DEAE cellulose chromatography is described whereby the main vitamin B12 binders in serum, gastric juice and saliva may be separated into two distinct fractions, one containing alpha-globulin binder and the other containing beta-globulin binder, in less than 2 hours. Typical elution patterns of alpha-globulin and beta-globulin B12 binders from normal (⅘ beta; ⅕ alpha), pernicious anemia (⅔ beta; ⅓ alpha), and chronic myeloid leukemia (CML) (¾ alpha) sera are presented. Chromatography of normal gastric juice produced two peaks of B12-binding material, one containing all the intrinsic factor (IF) B12 binder (as well as some non-IF binder), and the other consisting almost exclusively of non-IF B12 binders. Pernicious anemia gastric juice also produced two peaks, but IF was absent. Saliva had one main peak of B12-binding material which seemed to correspond to the non-IF binder of normal gastric juices; both of these eluted with the alpha-globulin fraction.
The Uptake of Fibrin and Fibrin-Degradation Products by the Isolated Perfused Rat Liver
Authors: GANS HENRY , LOWMAN JAMES T.
Published: October 2019

The uptake of Se75-labeled rat fibrin and a specific preparation of fibrin degradation products by an isolated, perfused liver was studied. The rapid phase T ½ for fibrin in the perfusate was approximately 9 minutes. This is comparable to that found for aggregated I131 B.S.A. and colloidal gold in the same system. The loss of activity from the blood closely paralleled the increased activity recorded in the liver. No radioactivity was found in the bile samples or the T.C.A.-soluble fraction of plasma. Microradioautographs of washed liver tissue following the labeled, fibrin perfusion suggest the presence of the label on or in the Kupffer cells.

Labeled rat fibrin preparations, digested by the action of "cold" rat plasmin to a distinct endpoint, were found to contain 3 distinct fractions on paper electrophoresis. Addition of these fractions to the perfusate resulted in approximately 25 per cent clearance of radioactivity over a 3-hour period. Hence, clearance of this specific F.D.P. preparation occurs at a much slower rate than that of fibrin. The T ½ as found to be in excess of 12 hours. These findings appear to confirm Lee’s observation that cells of the reticuloendothelial system are involved in the elimination of free circulating fibrin and its metabolic products.
Brief Report: The Di Guglielmo Syndrome: Studies in Hemoglobin Synthesis
Authors: NECHELES THOMAS F. , DAMESHEK WILLIAM
Published: October 2019

The in vitro synthesis of heme and globin has been studied in bone marrow cell suspensions obtained from five patients with Di Guglielmo syndrome. In all, a defect of heme synthesis was demonstrated, but globin synthesis was greatly reduced in only two of the five; in these two, the clinical course was a rapid one.
Reutilization of DNA Breakdown Products from Lymphocytes in Lumen of Intestine
Authors: KOTANI MASAHIKO , YAMASHITA AKIRA , RAI FUMIO , SEIKI KANJI , HORII ISOO
Published: October 2019

Migration of a very large number of lymphocytes (211.8 x 106 per day) into the intestinal canal of rats, which weighed about 100 Gm., was found. Lymphocytes in the lumen of the intestine were 80.2 per cent small, 15.9 per cent medium and 3.9 per cent large. Any recycling of instilling cells into the intestine could not be observed. Lymphocytes labeled with H3-thymidine, obtained from both thymus and mesenteric lymph nodes of donor rats, were washed and injected into the intestine of recipient rats. H3 activity of the blood and thoracic duct lymph plasma after administration of labeled lymphocytes showed that DNA breakdown products from the lymphocytes in the gut were absorbed and transferred by way of both the portal vein and the thoracic duct. Evidence that the activity was actually incorporated into the DNA of proliferating cells of the recipient was demonstrated by autoradiographic means.
Purification without Loss of Viability of Neoplastic Plasma-Cells from the Ascites Passaged Mouse Myeloma, X5563
Authors: GORDON BENJAMIN L. , FONG JACOB , PAPERMASTER BEN W.
Published: October 2019

A simple scheme for purification of murine myeloma cells from ascites fluid without loss of viability is presented. This is accomplished by repeated differential centrifugations followed by passage through a glass bead column. The cells so obtained are 99.9 per cent pure and 99 per cent viable in a large number of repetitions of this technic.
Folate Deficiency Associated with Drug Therapy for Tuberculosis
Authors: KLIPSTEIN FREDERICK A. , BERLINGER FREDERICK G. , REED L. JUDEN
Published: October 2019

Two patients have been described who were found to have a megaloblastic anemia due to folate deficiency while receiving treatment for pulmonary tuberculosis with isoniazid and cycloserine. In an additional 120 patients studied with tuberculosis, serum folate concentrations were subnormal in 7 of 12 inadequately nourished and in 5 of 24 well-nourished patients with untreated tuberculosis, in 15 of 29 patients taking isoniazid and cycloserine, but in only 2 of 55 patients receiving other combinations of drugs for tuberculosis. In vitro studies showed that isoniazid had a depressant effect on the growth of L. casei but only when added in a concentration that greatly exceeded the pharmacologic dose; cycloserine had a similar effect at a concentration that was only threefold greater than that usually found in patients receiving therapeutic doses of this drug.

Serum concentrations of vitamin B12 were normal in both patients described with megaloblastic anemia as well as in all 36 patients with untreated tuberculosis and were in the indeterminate range in 14 and subnormal in 3 patients who were receiving drug therapy. The addition to medium in vitro of cycloserine, but not of isoniazid or pyrazinamide depressed the growth of L. leichmannii.

These results confirm previously reported observations by others which indicate that folate deficiency is a frequent occurrence in patients with untreated tuberculosis. They suggest that abnormal folate determinations in these patients are due principally to inadequate dietary intake. In addition, the significantly greater incidence of abnormal folate determinations that was observed in adequately nourished patients taking cycloserine and the results of the in vitro studies suggest that this drug can be responsible for folate deficiency in some instances. The mechanism for this is unknown.
Studies on the Mechanism of in Vitro Acid Hemolysis in Paroxysmal Nocturnal Hemoglobinuria
Authors: SCOTT J. G. , WEED R. I. , SWISHER S. N.
Published: October 2019

1. The mechanism of acid hemolysis of PNH erythrocytes appears to be a direct mechanism, with the production of an initial "hole" in the membrane sufficiently large to permit the direct egress of hemoglobin.

2. PNH erythrocytes react like normal red cells with rabbit antihuman red cell antibody and human or guinea pig C' at pH 7.2 to produce a membrane defect which is less than 32.5 Å in effective diffusion radius.

3. Inhibition of acid hemolysis of PNH erythrocytes by high molecular weight dextrans (Dextran 150) is also associated with inhibition of K+ loss, indicating inhibition of complement.
Observations on Fe59 Labeled Bone Marrow Ferritin
Authors: GABUZDA THOMAS C. , GARDNER FRANK H. , Council Anne
Published: October 2019

Qualitative studies were carried out to determine the nature of the nonhemoglobin protein or proteins of human bone marrow which incorporate radioiron during in vitro incubations of this tissue. The labeled fraction was studied chiefly by following the behavior of the radioactive iron and comparing it with ferritin isolated from human spleen. Two types of labeled ferritin were identified in the nonhemoglobin fraction. One, a "fast" ferritin, was of greater electrophoretic mobility than spleen ferritin in starch granules and appeared possibly to be the chief incorporator of transferrin-bound iron. The second, or "slow" ferritin, was identical in electrophoretic mobility with spleen ferritin and contained only a tiny percentage of the radioiron incorporated into "fast" ferritin. No other iron-labeled nonhemoglobin components were observed, although their possible presence cannot be discounted.
Electron Microscopic Study of Human Basophils
Authors: ZUCKER-FRANKLIN DOROTHEA
Published: October 2019

Electron microscope studies were carried out on human basophils obtained from peripheral blood and thoracic duct lymph. Delineation of the cells in thick sections was facilitated by staining with Toluidine Blue, which imparted the characteristic purple-red color to the granules. The cytoplasm contains many of the organelles seen in other cells, including a small Golgi apparatus, centrioles, mitochondria, fibrils and microtubules. Ribosomes and rough ER are rarely encountered. Basophil granules are surrounded by a unit membrane and contain particles which are uniform in size within the same granule but which vary in size in different granules within the same cell. Some granules reveal a homogeneous texture and/or "myelin" figures. The appearance of most basophil granules differs from the ultrastructure of human mast cell granules reported to date. It is suggested that the difference in fine structure may reflect a difference in the chemical constituents of the granules.
The Effect of Diisopropylfluorophosphonate (DFP) on Platelet Survival in the Rabbit
Authors: CHANG YI-HAN
Published: October 2019

Diisopropylfluorophosphonate was found to influence platelet survival. The possible mechansims of action and the importance of standardizing the amount of DFP32 administered in platelet survival experiments are discussed.
Brief Report: Erythrocyte Enzymes in Polycythemia Vera
Authors: BARTOS HENRY R. , DESFORGES JANE F. , Samanvicius Dalia
Published: October 2019

Erythrocyte glutamic oxalacetic transaminase (EGOT), glucose-6-phosphate dehydrogenase (G-6-PD), and hexokinase were found to be increased in patients with polycythemia vera. This suggests the presence of a population of erythrocytes younger than normal in these patients. The pathogenesis of this phenomonon is unclear but several possible mechanisms are suggested.
STUDIES ON BONE MARROW IN VITRO
Authors: ROSIN A. , RACHMILEWITZ M.
Published: October 2019

The effect of various oxygen tensions on explanted bone marrow fragments was studied. It was found that gas mixtures containing 1, 3, 5, 10 and 12 per cent oxygen have an injurious effect on hemic cells. Bone marrow maintained in these gas mixtures showed various degrees of degeneration, which was the more pronounced the lower the oxygen tension. Mitotic activity was also found to be reduced under the influence of low oxygen tension.

Bone marrow cultures maintained in a gas mixture containing 15 per cent oxygen did not show appreciable changes and were similar to the controls.

Increased rate of maturation and multiplication occurred in bone marrow cultures maintained in an excess of oxygen, i.e. 50 per cent.

The significance of these findings in the light of observations on the effect of anoxia in vivo has been discussed, and reported findings on the effect of low oxygen tensions on other tissues in vitro have been briefly reviewed.
Tissue Distribution of Radio-B12 after Intravenous Injection of Gastric Juice, Saliva and Plasma-Bound Co57 B12
Authors: ROSENTHAL WILLIAM S. , WEISBERG HERBERT , GLASS GEORGE B. JERZY
Published: October 2019

Co57B12 bound to pernicious anemia gastric juice was administered intravenously to 4 normal individuals, and Co57B12 bound to autologous plasma was administered to 2 of these. Hepatic, arm and blood radioactivity were measured for one week and compared with that following the intravenous injection of unbound Co57B12. Pernicious anemia gastric juice increased hepatic uptake, delayed blood clearance and decreased arm uptake of Co57B12 as compared with Co57B12 injected unbound or bound to plasma. Thus, the B12 bound to gastric juice is retained longer in the intravascular space with greater uptake by liver.

These results suggest that gastric juice B12 binders, but not plasma B12 binders, enhance hepatic B12 uptake either by acting at specific receptor sites on the liver cell membrane or by retaining B12 longer in circulation. This property of gastric juice B12 binders is not related to IF activity but is rather dependent upon some structural or functional feature common to both IF-related and nonrelated B12 binders of gastric juice.
Carbonic Anhydrase and Fetal Hemoglobin in Thyrotoxicosis
Authors: ENG LIE-INJO LUAN , HOLLANDER L. , FUDENBERG H. HUGH
Published: October 2019

An adult patient with thyrotoxicosis had erythrocyte carbonic anhydrase deficiency and an abnormally high level of fetal hemoglobin. After treatment of the hyperthyroidism, the erythrocyte carbonic anhydrase level became normal and the level of Hb F dropped. Twelve other patients with hyperthyroidism and not related to this index case were studied. Most of them were already under treatment. Nine had erythrocyte carbonic anhydrase deficiency; two had an increase of fetal hemoglobin. The possible relationship of increase of fetal hemoglobin, erythrocyte carbonic anhydrase deficiency and thyrotoxicosis is discussed.
Leukocyte Lysozyme Activity in Myelocytic Leukemia
Authors: NOBLE R. E. , FUDENBERG H. HUGH
Published: October 2019

Leukocyte and serum lysozyme activity was determined in nine patients with acute myeloblastic or chronic myelocytic leukemia and in 20 normal control subjects. Biochemical assay and quantitative estimation of leukocyte lysozyme activity in the patients demonstrated a parallel in general between the maturity of the granulocytes and their lysozyme content. Such determinations appear to provide a quantitative index of the extent of the leukemic process in the peripheral granulocytes and therefore should be of value as a guide to prognosis in these disorders.
Polycythemia Vera with Ph1 Chromosomes in Two Brothers
Authors: LEVIN WILLIAM C. , HOUSTON ELSIE W. , RITZMANN STEPHAN E.
Published: October 2019

Two brothers with polycythemia rubra vera have been studied: one before treatment and one after many years of treatment. Direct harvests of marrow aspirates from both patients exhibited the presence of the Ph1 chromosome. Moderately increased LAP levels were present in both. Available data do not indicate whether the disease and the chromosomal aberrations in these two brothers are familial or fortuitous.
The Chronology of the Mitotic Cycle of Human Granulocytopoietic Cells Phase Contrast Studies on Living Cells in Vitro
Authors: RONDANELLI E. G. , MAGLIULO E. , GIRALDI A. , CARCÒ F. P.
Published: October 2019

Data on the mitotic index of human granulocytopoietic cells are presented. From these and from the duration of mitosis directly measured in living cells by phase contrast microscope, the weighted average generation time and the mean compartment transit time are computed. Maturation in granulocytopoietic cells appears to induce a reduction of mitotic indices and mitotic rate and an increase in mitotic time and in mean compartment transit time. Part of the increment in mitotic duration may be due to the acquisition by a part of the granulocytopoietic cells of cytoplasmic peripheral motility or other specialized activities, thus distracting part of the energies destined to mitosis.
Experimental Hemostasis in Normal Dogs and Dogs with Congenital Disorders of Blood Coagulation
Authors: HOVIG T. , ROWSELL H. C. , DODDS W. J. , JØRGENSEN L. , MUSTARD J. F.
Published: October 2019

Hemostasis was examined after transection of vessels, 50-200 microns in diameter, both in normal dogs and in dogs with congenital defects of either factor VII, factor IX, or factor VIII. The formation of the hemostatic platelet plugs was observed by direct microscopy in vivo, and sections of the plugs were prepared for both light and electron microscopy 10 to 30 minutes after transection. Furthermore, the reaction of platelets from normal and abnormal dogs with adenosine diphosphate, collagen and thrombin was tested in vitro by a turbidimetric technic.

In normal and factor VII deficient dogs the initial arrest of bleeding took place about 3 minutes after transection, and rebleeding was infrequently observed. Their platelet plugs were composed of densely packed platelets, anchored to the vascular and perivascular tissue and surrounded by a cap of fibrin.

In factor IX deficient dogs there was no definite prolongation of the initial bleeding time, but rebleedings were frequent. In factor VIII deficient dogs the initial bleeding time was prolonged and the intensity of the bleeding had a wave-like characteristic. The plugs in the hemophilic dogs were larger than normal, were rich in channels, and had areas of loosely packed platelets and an incomplete fibrin cap.

Treatment of factor IX deficient dogs with Dicumarol did not further impair hemostatic plug formation in the doses used. Treatment of factor VII deficient dogs with heparin, or factor IX deficient dogs with phenylbutazone, prolonged the bleeding time markedly, delayed the building up of the plug, and gave fragile, loosely packed plugs. Treatment of normal dogs with phenylbutazone did not alter the hemostatic process at the dosage used.

In the in vitro studies, platelets from the dogs with congenital coagulation defects reacted normally with the aggregating stimuli.

It is concluded that the initial platelet interaction wih the vessel wall and surrounding tissue is not dependent upon blood coagulation. An intact intrinsic pathway of coagulation is necessary for the stabilization of the hemostatic plug after it is formed.
Some Effects of Artificial Media upon Glycolysis in Rat Platelets
Authors: ROSSI ENNIO C. , Volk Edith
Published: October 2019

The effect of artificial media upon glycolysis of rat platelets was studied. Isotonic saline did not support glycolytic activity in platelets because of its acid pH. Although buffering the media to pH 7.4 established platelet glycolysis, the choice of buffer affected the results. Tris buffer or 25 mM phosphate buffer did not alter glucose consumption, lactate production, or adenosine triphosphate (ATP) concentration in platelets from that observed when platelets were incubated in plasma. However, use of 75 mM phosphate buffer produced significant increases in both glucose consumption and lactate production by platelets. A more marked effect was associated with imidazole which not only increased glucose consumption and lactate production but also accelerated the loss of platelet ATP.
BRIEF REPORT: Absence of Hemoglobin A in a Double Heterozygote for F-Thalassemia and Hemoglobin S
Authors: STAMATOYANNOPOULOS C. , SOFRONIADOU C. , AKRIVAKIS A.
Published: October 2019

An adult with minor hematologic abnormalities and hemoglobin electrophoretic pattern characterized by large amounts of hemoglobins S and F together with absent hemoglobin A, was shown to be doubly heterozygous for F-thalassemia and hemoglobin S. Absence of Hb A in this double heterozygote provides further evidence that in F-thalassemia the suppression of the β-chains in cis position is complete.
BRIEF REPORT: Freeze-Cleaving of Red Cell Membranes in Paroxysmal Nocturnal Hemoglobinuria
Authors: WEINSTEIN RONALD S. , WILLIAMS ROGER A.
Published: October 2019

Electron microscopic studies on dried isolated red cell ghosts have been reported to show lesions associated with cell membranes in paroxysmal nocturnal hemoglobinuria (PNH). In this study, carbon-platinum replicas of membranes of freeze-cleaved, partially hydrated PNH red cells and isolated PNH cell ghosts failed to confirm the existence of these abnormalities. This suggests that the previously described lesions are the products of drying artifacts, although they may reflect hidden structural differences between PNH and normal red cell membranes.
Extracorporeal Irradiation of Blood (ECIB) in Man
Authors: SCHIFFER L. M. , ATKINS H. L. , CHANANA A. D. , CRONKITE E. P. , GREENBERG M. L. , STRYCKMANS P. A.
Published: October 2019

Fourteen adults with acute myelocytic leukemia (AML) received 16 courses of extracorporeal irradiation of the blood (ECIB). The median survival time of 8.0 months, taking into consideration many of the variable factors, was as good as, if not better than, studies previously reported despite the absence of hematologic remissions. This group of patients is small, however, and no definitive evaluation of ECIB treatment for AML can be made. Although no significant bone marrow changes were noted, there was a marked decrease in the peripheral leukemic cells of 75 per cent of the patients. There appears to be a correlation of increased survival time with a transit dose of ECIB over 340 rads. At the present time, the usefulness of this mode of treatment in the overall management of AML is uncertain, although it might be considered as an alternative form of therapy for patients in whom chemotherapy is contra-indicated and to prevent leukostasis. When used, the possibility of complications related to the shunt should always be borne in mind.
The Relationship of Plasma Fibrinogen (Factor I) Level to Fibrin Stabilizing Factor (Factor XIII) Activity
Authors: ALAMI SAMIH Y. , HAMPTON JAMES W. , RACE GEORGE J. , SPEER ROBERT
Published: October 2019

The relationship of fibrinogen concentration to Factor XIII activity in the plasmas of 110 subjects (90 patients and 20 healthy volunteers) was studied. No definite, consistent, predictable relationship could be established. However, in certain pathological conditions, with hyper- or hypofibrinogenemia, a moderate reduction in Factor XIII activity may be present, and usually occurs without hemorrhagic manifestations. On the other hand, examination of normal plasmas artificially enriched with large amounts of bovine fibrinogen revealed no changes in Factor XIII activity. In the light of these observations, the suggestion is made that reduced Factor XIII activity may be encountered in certain disease conditions without simultaneous changes in fibrinogen concentration. The site of synthesis of these two proteins, although most likely the liver, would appear to not influence their plasma concentrations simultaneously.
Red Cell Hypoplasia, Cold Hemoglobinuria and M-Type Gamma G Serum Paraprotein and Bence Jones Proteinuria in a Patient With Lymphoproliferative Disorder
Authors: PRASAD ANANDA S. , BERMAN LAWRENCE , TRANCHIDA LIBORIO , POULIK M. DAVE
Published: October 2019

This paper documents an unusual example of hypoplastic anemia, intermittent hemoglobinuria appearing in cold weather, and lymphoproliferative disease associated with hypogammaglobulinemia and repeated infections, followed by the appearance of a monoclonal gammopathy (IgG-Kappa) and Bence Jones proteinuria (Kappa), with tissue lesions more characteristic of macroglobulinemia than of multiple myeloma, in a middle-aged Negro.
Absolute Rates of Globin Chain Synthesis in Thalassemia
Authors: BANK ARTHUR , BRAVERMAN ALBERT S. , O’DONNELL JOYCE V. , MARKS PAUL A.
Published: October 2019

The absolute rate of α chain synthesis per erythroid cell in the peripheral blood of patients with β thalassemia has been shown to be normal while that of β chains is markedly decreased or absent. The results indicate that α chains do not require the presence of β chains for their normal synthesis and release. In addition, γ chain synthesis does not compensate for the decreased β chain synthesis. A marked heterogeneity in the amount of β globin chains produced by different patients with β thalassemia is also prominent.
A Study of Erythropoiesis by Combined Morphologic, Quantitative Cytochemical and Autoradiographic Methods
Authors: WICKRAMASINGHE S. N. , COOPER E. H. , CHALMERS D. G.
Published: October 2019

The relationship between the morphology of human erythropoietic cells and their position in interphase has been studied. In normal bone marrow, pro-normoblasts, basophilic normoblasts and early polychromatic normoblasts were present in all stages of interphase. It has been shown that a significant increase in nuclear size occurs as a cell moves through its cell cycle, in both normal and megaloblastic erythropoiesis.

The relative distribution of the basophilic erythropoietic cells and the dividing polychromatic cells, in the various stages of interphase, has been determined in normal bone marrow, vitamin B12 deficiency and iron deficiency anemia.

In vitamin B12 deficiency, associated with moderate or severe anemia, there was an increased proportion of cells in G2, and there were several cells with DNA contents that were between the 2c and 4c values, which were not in DNA synthesis as judged by 3H-TdR labeling. These abnormalities were most pronounced in the dividing polychromatic cell group. Similar abnormalities were not present in iron deficiency anemia, indicating that these disturbances were not produced by the presence of anemia per se. The possible relationship between these changes in the cell cycle and the ineffective erythropoiesis seen in anemia due to vitamin B12 deficiency has been discussed.
Appearance of Platelet-Clumping Substance after Acidification of Plasma
Authors: YAMAZAKI HIROH , MURASE HIROSHI , SHIMAMOTO TATSUO , SHIMAMOTO TAKIO
Published: October 2019

1. The pH values of heparinized plasma from ten normal rabbits were from 7.53 to 7.80. The average pH and standard error was 7.69 ± 0.03. These plasmas did not show platelet-clumping activity when exposed to the platelet-saline suspension from the same or other normal rabbits. The platelet-clumping substance was not observed in all ten cases after alkalinization of the plasma to pH values ranging from 8.32 to 9.40. On the contrary, immediately after acidification of the plasmas, the platelet-clumping substance appeared at pH values from 4.90 to 6.82 at room temperature. The range of the lower pH value, in which the platelet-clumping substance was observed, was 4.90-5.60 (5.15 ± 0.07 in average) and the upper range was 5.95-6.82 (6.27 ± 0.12 in average). The pH range at which the strongest clumping of platelets appeared was 5.22-5.95 (5.61 ± 0.07 in average). The platelet-clumping substance did not disappear after the pH of the acidified plasma was reneutralized to the original value.

2. No clumping was found after the addition of citrated, oxalated, EDTA-plasma or serum even when they were acidified. After the pH value of the citrated, oxalated or EDTA-plasma was changed from 4.85 ± 0.39 to 7.55 ± 0.03 and in the presence of calcium ions (10 mM.), platelet-clumping activity was observed. After the addition of citrate (0.38 percent in final concentration), oxalate (0.2 percent in final concentration), or EDTA (0.1 percent in final concentration) to the heparinized plasma the platelet-clumping substance did not disappear. In the case of serum, the platelet-clumping activity did not appear after the pH changes.

3. The platelet-clumping substance in the acidified plasma was heat-labile; it was detected after BaSO4-adsorption and defibrination; it was stable in storage at 4 C., and it was not dialyzable against Ringer’s solution for 72 hours. It induced platelet clumping not only in citrated platelet-rich plasma but also in the platelet-saline suspension.

4. The properties of the platelet-clumping substance in the acidified plasma were compared with that of substances known to have platelet-clumping activity and the experimental evidences showing the differences to ADP, thrombin, ADP-cofactor and thrombocyte agglutinating factors have been detailed.
Brief Report: The Catabolism of Heinz Bodies: An Experimental Model Demonstrating Conversion to Non-Bilirubin Catabolites
Authors: GOLDSTEIN GARY W. , HAMMAKER LYDIA , SCHMID RUDI
Published: October 2019

Hemoglobin and solubilized Heinz bodies whose heme moiety had been labeled with C14, and C14-hemin were infused into rats with an external bile fistula. The fractional conversion of these heme pigments to bilirubin was estimated from the amount of C14-bilirubin excreted in the bile.

Whereas a major fraction of the native hemoglobin and intact hemin was converted to bilirubin, the heme moiety of the Heinz bodies was broken down to diazo- and benzidine-negative, water- and butanol-soluble metabolites which were excreted in the bile and, to a lesser extent, in the urine. These excretory products had the solubility and spectroscopic properties of mesobilifuscins, but their exact chemical configuration could not be determined.

The findings indicate that oxidative denaturation of hemoglobin is associated with structural alterations of the heme moiety that favor its catabolism by a pathway in which bilirubin is neither an intermediate nor an end product. The significance of this alternate metabolic pathway for the overall turnover of hemoglobin and other heme proteins is discussed.