bluuebunny/crossref_metadata_2025 huggingface dataset:
Heinz Body Anemia—An Ultrastructural Study. I. Heinz Body Formation
Authors: RIFKIND RICHARD A. , DANON DAVID
Published: October 2019

The ultrastructural changes in red blood cells exposed to phenylhydrazine, either in vivo or in vitro, are described. There is an age-dependent gradient of red cell sensitivity to this drug which includes the more mature reticulocytes as well as the population of circulating erythrocytes. Oxidative denaturation of hemoglobin and the formation of Heinz bodies, which constitute the major drug-induced lesion, are accompanied by a regular sequence of structural changes commencing in the central cytoplasm of erythrocytes and the drug-sensitive reticulocytes. These early changes often appear in close associaion with clusters of mitochondria. The initial morphologic lesion has an apparently crystalline structure and the significance of this stage is discussed. Heinz bodies grow by coalescence and condensation and finally come to lie just beneath the cell surface. Here they result in considerable distortion of cell shape and deformation of the plasma membrane. Thus, phenylhydrazine administration produces in red blood cells extensive ultrastructural alterations both in hemoglobin and in the cell membrane which may have considerable bearing on the fate of these cells in the circulation.
Renal Mechanism for Excretion of Porphyrin Precursors in Patients with Acute Intermittent Porphyria and Chronic Lead Poisoning
Authors: DRUYAN ROBERT , HAEGER-ARONSEN BIRGITTA , VON STUDNITZ WILFRIED , WALDENSTRÖM JAN
Published: October 2019

Serum concentrations of ALA and PBG have been measured in normal subjects, patients with AIP, and lead workers. Both porphyrin precursors are significantly increased in serum from porphyric patients, and serum ALA is elevated in lead workers. Endogenous clearance measurements, when compared with creatinine clearances, are consistent with significant tubular reabsorption of ALA and PBG under physiologic circumstances, and with an "overflow" mechanism for increased excretion in AIP or lead intoxication. Three of 8 porphyric patients showed an aminoaciduria; tyrosine was involved in 2, tryptophan in the other 3. Evidence to suggest a specific renal defect contributing to increased ALA excretion in chronic lead intoxication was not obtained.
A Case of Prolonged Thrombocytopenia in Childhood Terminating in Leukemic Reticuloendotheliosis
Authors: GALLOWAY COLIN A. S. , INNES ELIZABETH M.
Published: October 2019

The case history is reported of a 2-year-old boy who presented with persistent thrombocytopenia, developed a leukoerythroblastic blood picture at 7½ years and died at 9 years of leukemic reticuloendotheliosis. His mother died of acute lymphatic leukemia shortly after the birth, and some of the hereditary aspects of leukemia are discussed. It is suggested that the thrombocytopenia represented a preleukemic state, of unusually long duration, and that this and the leukemic reticuloendotheliosis were different phases of the same basic disorder. The surmise is made that heredity may play a part in the etiology of leukemic reticuloendotheliosis in childhood, a period of life when this disorder is very rare.
Circulating Megakaryocytes and Platelet Release in the Lung
Authors: KAUFMAN RICHARD M. , AIRO ROMANO , POLLACK SIMEON , CROSBY WILLIAM H.
Published: October 2019

1. Megakaryocytes were demonstrated in central venous blood of each of 23 patients who underwent cardiac catheterization. Cell counts ranged from 0.7 to 5.9 megakaryocytes per ml. of blood; the equivalent of one-third of these cells were considered to contain a full complement of cytoplasm. It has become evident that megakaryocytes are normal constituents of blood.

2. In an attempt to quantify megakaryocyte migration from the bone marrow it was calculated that from 20-50 per cent of the mature megakaryocyte population enters the blood and ultimately reaches the lungs. The possibility that all megakaryocytes migrate from the marrow is not precluded with certainty by these studies.

3. It was estimated that from 7-17 per cent of the body’s platelets are released in the pulmonary capillaries. If all megakaryocytes migrate from the bone marrow, then as much as 33 per cent of the platelet population is delivered to the blood in the lungs.
Prolonged Remission in Chronic Myeloid Leukemia after One Course of Busulfan
Authors: DJALDETTI MEIR , PADEH BARUCH , PINKHAS JACK , DE VRIES ANDRE
Published: October 2019

A patient with chronic myeloid leukemia in whom a clinical and hematologic remission of nearly 7 years duration occurred after a single short course of busulfan is described. The only abnormal finding during the remission was a negative alkaline phosphatase reaction in her leukocytes. Chromosomal studies prior to relapse revealed a normal karyotype, and no Philadelphia chromosome was found. During relapse renewed chromosomal study revealed Philadelphia chromosome in metaphases of peripheral blood leukocytes.
The Oxidation of Long-Chain Fatty Acids by the Formed Elements of Human Blood
Authors: ROSENZWEIG ARNOLD , WAYS PETER
Published: October 2019

1. In vitro, human erythrocytes free of contaminating white cells and platelets do not oxidize fatty acid in the surrounding medium, either bound to albumin or supplied in buffer as the potassium salt. These results are not influenced by glucose deficiency.

2. White cells and platelets are both capable of oxidizing fatty acid from the surrounding medium—supplied either as the potassium salt in buffer or bound to albumin. Increasing the albumin/fatty acid molar ratio results in a decrease in the quantity of fatty acid oxidized. The amount of fatty acid oxidized is greater if glucose is not added to the medium.
Brief Report: Two Bence Jones Proteins of Different Immunologic Types in the Same Patient with Multiple Myeloma
Authors: ENGLE RALPH L. , NACHMAN RALPH L.
Published: October 2019

In summary, two Bence Jones proteins, one of type K and the other of type L immunologic specificity, and a serum myeloma protein of type L were demonstrated in the same patient with multiple myeloma. It is probable that, in this instance, dissemination from at least two clones of plasma cells has occurred.
The Effect of Ellagic Acid on Coagulation in Vivo
Authors: GIROLAMI ANTONIO , AGOSTINO DOMENICO , CLIFFTON EUGENE E.
Published: October 2019

Ellagic acid shortens the silicone and glass clotting times of the blood of dogs, cats, rabbits and rats. The silicone clotting time is reduced so as to make it almost equal to the normal glass clotting time for 5 to 30 minutes after the injection of the agent. There is occasional acceleration of thromboplastin generation in dogs. No other clotting factors were altered significantly in our experiments.

There were no obvious toxic effects of ellagic acid, and it appears to decrease bleeding in normal animals.
Brief Report: Erythropoiesis after Exchange Transfusion in Hemolytic Anemia
Authors: ERSLEV ALLAN J. , MCKENNA JOSEPH P.
Published: October 2019

Exchange transfusion with preservation of a constant hemoglobin concentration in three patients with hereditary spherocytosis, and one patient with acquired hemolytic anemia did not result in any significant change in the rate of red cell production as measured by serum iron turnover and bone marrow examinations. These observations support the hypothesis that tissue hypoxia controls red cell production.
A Controlled Trial of Urethane Treatment in Multiple Myeloma
Authors: HOLLAND JAMES F. , HOSLEY HENRY , SCHARLAU CAROL , CARBONE PAUL P. , FREI EMIL , BRINDLEY CLYDE O. , HALL THOMAS C. , SHNIDER BRUCE I. , GOLD G. LENNARD , LASAGNA LOUIS , OWENS ALBERT H. , MILLER SHERWOOD P.
Published: October 2019

Patients with multiple myeloma were stratified according to prior treatment and randomly assigned to coded urethane or placebo syrup administration. Urethane administration was of shorter duration than placebo treatment, but was associated, in patients who received 100 Gm. or more, with leukopenia in the last half of treatment courses. All recognizable beneficial effects were extracted from individual case histories and were found to be nearly equally distributed between the two treatments. Interpretation of the causes of clinical benefit was difficult but there was close temporal relationship to radiation, antibiotics for infection, or corticosteroid administration. Some clinical features and laboratory data of 36 patients with placebo-treated multiple myeloma are provided.

Urethane-treated patients died somewhat earlier on the average than those treated with placebo. This was ascribable in large part to accelerated mortality in urethane-treated patients who were azotemic.

When hemoglobin concentration, marrow plasma cell content, performance status and azotemia were used to construct a relative ranking prognostic index, among the two-thirds of patients with the worst indexes significantly shorter survival was associated with urethane treatment (p < .05). In the best prognostic class, no difference was observed in the survival of urethane- or placebo-treated patients.

Since urethane administration was in no way superior to placebo administration, and was characterized by shortened survival, its use in the doses and schedule employed in this study would appear ill advised.
Quantitative and Qualitative Aspects of Steady State Erythropoiesis Induced in Protein-Starved Rats by Long-Term Erythropoietin Injection
Authors: ITO KENJIRO , REISSMANN KURT R.
Published: October 2019

Protein starvation nearly arrested erythropoiesis in rats, and the red cell mass decreased during a period of 32 days from 4.0 to 2.5 ml. Protein-starved rats, injected daily with 1.8 units of rabbit erythropoietin, had reticulocyte counts within the normal range, and their cell mass increased during the same period to 4.26 ml., as compared to 4.52 ml. in normal controls. Red cell indices, Price-Jones curve and osmotic fragility were normal on blood obtained from erythropoietin-treated groups. Differential counts on their erythroid marrow composition were not significantly different from those in normal rats. It is concluded therefore that daily injection of 1.8 units of rabbit erythropoietin induced, over a period of 32 days, a steady state erythropoiesis which, on the basis of the parameters studied, could not be distinguished from that in normal rats. No evidence of a shortened lifespan of cells formed in response to erythropoietin was found after either random (Cr51) or cohort (Fe59) labeling. Random labeled (Cr51) cells from untreated protein-starved rats had significantly shorter chromate survival times than cells from normal or erythropoietin-treated rats. The difference is attributed to the altered age distribution in their red cell population.
Döhle Bodies Associated with Uncomplicated Pregnancy
Authors: ABERNATHY MAX R.
Published: October 2019

Döhle bodies have been described in the neutrophilic leukocytes of uncomplicated gravid women. Of 500 blood films screened from uncomplicated pregnancies, all but 9 exhibited Döhle bodies. Serial studies of 15 uncomplicated pregnancies, followed throughout all 3 trimesters and for 6 to 8 weeks postpartum, repeatedly showed Döhle bodies. No Döhle bodies were found in the leukocytes of the 500 normal nonpregnant women used as a control.

The appearance of Döhle bodies in uncomplicated pregnancy and their relationship with the inclusions found in various states are unexplained.
Lymphatic Drainage of Thymocytes to the Circulation in the Guinea Pig
Authors: KOTANI MASAHIKO , SEIKI KANJI , YAMASHITA AKIRA , HORII ISOO
Published: October 2019

1. An extensive network of lymphatic vessels coming from the thymus of the guinea pig and carrying thymocytes to the general circulation has been demonstrated.

2. Local accumulations or infiltrations of cells at the surface of the lobule or in the interlobular septa have been observed through which thymocytes appear to leave the thymus.

3. Irregular, tortuous canaliculi, resembling a lymph sinus in a lymph node, seem to play an important role in transporting thymocytes from these accumulations to the typical lymphatic vessels.

4. The output of thymocytes via lymphatic vessels to the general circulation is about 12.1 x 106 per day.
Extracorporeal Irradiation of the Blood in Humans: Effects upon Erythrocyte Survival
Authors: SCHIFFER LEWIS M. , ATKINS HAROLD L. , CHANANA ARJUN D. , CRONKITE EUGENE P. , GREENBERG MICHAEL L. , JOHNSON HORTON A. , ROBERTSON JAMES S. , STRYCKMANS PIERRE A.
Published: October 2019

Autologous erythrocytes were irradiated at doses of 35,000 to 200,000 rads, chromated, and red cell survival studied. The 24-hour loss of labeled cells and subsequent apparent erythrocyte survival times were found to be functions of the radiation dose. ECIB-produced red cell hemolysis of a mild degree is to be expected during courses of therapy, as demonstrated by clinical findings. However, there is no doubt that acute, severe, hemolysis could be produced by administering large doses to patients over a short period of time.
Multiple Myeloma and Normal Pregnancy
Authors: KOSOVA LEONARD A. , SCHWARTZ STEVEN O.
Published: October 2019

Pregnancy of a patient with multiple myeloma and the subsequent uncomplicated delivery of a viable normal infant apparently is the first such case reported. The child is developing normally. The mother died almost 9 months after delivery. Serum electrophoretic and immunoelectrophoretic data are documented. The primary protein abnormality in the mother was the excessive production of a γA globulin.
Fe59 Absorption in Human Subjects Using Total-Body Counting Technic
Authors: POLLACK SIMEON , BALCERZAK STANLEY P. , CROSBY WILLIAM H.
Published: October 2019

In most procedures utilizing total body counting to measure iron absorption in humans, the assumption is made that iron located in the gastrointestinal tract is counted with the same efficiency as Fe59 distributed throughout the body. This assumption was found to be in error in a significant number of subjects.
The Chediak-Higashi Syndrome: A Possible Lysosomal Disease
Authors: WHITE JAMES G.
Published: October 2019

All varieties of circulating white blood cells in patients with Chediak-Higashi syndrome characteristically contain giant granules in their cytoplasm. The similarity of the massive particles to normal-sized leukocyte lysosomes has been previously recognized. In the present study the technics of ultrastructural histochemistry were used to demonstrate acid phosphatase activity in giant C.H. particles and their degenerating remnants in the leukocytes of two patients with the C.H. syndrome. The presence of an acid hydrolase in massive granules indicates that they are lysosomes. The selective localization of enzyme reaction product in large particles by this method, when small normal-appearing lysosomes in the same cells remained unstained, has suggested that the unit membranes surrounding C.H. granules are abnormally permeable. The increased permeability of the large particles may be related to the pathogenesis of morbid clinical features of C.H. syndrome.
Extraction of an Erythropoietin-Producing Factor from a Particulate Fraction of Rat Kidney
Authors: CONTRERA JOSEPH F. , GORDON ALBERT S. , WEINTRAUB ARTHUR H.
Published: October 2019

1. A two-step method for the extraction of erythropoietin from hypoxic kidneys has been developed which allows residual plasma erythropoietin in renal vasculature to be separated from that of intracellular origin.

2. Renal extracts have been purified by DEAE cellulose chromatography and found to contain 2 major erythropoietically active fractions. One bears strong resemblance to plasma erythropoietin. The other component is unique in that it has practically no erythropoietic-stimulating activity unless previously incubated with normal rat serum. This activation phenomenon is used to identify this kidney component as the renal erythropoietic factor (REF). The REF has the capacity to produce erythropoietin or become erythropoietically active when incubated with normal rat serum.

3. Differential centrifugation technics revealed that the REF is confined to particles present in the light mitochondrial fraction of kidney.

4. Extracts of the light mitochondrial fraction of kidneys from normal rats produced significant amounts of erythropoietin when incubated with normal serum. The quantity found, however, was less than that evoked by similar extracts of kidneys from hypoxic rats.

5. The product of the incubation extracts of the renal light mitochondrial fraction with normal rat serum showed the same log dose/response regression as sheep plasma erythropoietin standard.

6. It is hypothesized that either (a) the REF is a precursor of erythropoietin which must be complexed with a carrier present in normal serum in order to become physiologically active, or (b) the renal factor is an enzyme which produces erythropoietin by its action on a particular serum protein.
Immunologic Aberrations in the Di Guglielmo Syndrome
Authors: FINKEL HARVEY E. , BRAUER MARK J. , TAUB ROBERT N. , DAMESHEK WILLIAM
Published: October 2019

Immunologic studies were performed in 49 patients with the Di Guglielmo syndrome. Although altered immune reactivity has not been previously thought to be a feature of myeloproliferative disorders, more than one-third of the cases showed immunologic aberrations. The abnormalities encountered included overproduction of antibody protein (hypergammaglobulinemia) and an increased tendency to form rheumatoid factor, LE factor (including one case with overt systemic lupus), positive serologic tests for syphilis, and erythrocyte autoantibodies and isoantibodies.

Possible pathogenetic mechanisms are considered. The underlying neoplastic process might directly involve the immunocytes, resulting in exaggerated and nonspecific responses, or in defective self-recognition and thus in the production of autoantibodies. Alternatively, preexisting but "hidden" antigens might be exposed by the proliferative disorder, thus stimulating an antibody response. Finally, and perhaps most likely, antigenic alteration of bone marrow tissue might accompany its neoplastic transformation. Such tissue could be recognized as "not-self" or "foreign" by a qualitatively normal immune system. This would result in the production of abnormal proteins, some of which would be immunologically effective.
Isolated Malabsorption of Vitamin B12 Causing Megaloblastic Anemia and Hyperpigmentation in a Nigerian
Authors: WATSON-WILLIAMS E. J. , FLEMING A. F.
Published: October 2019

A Nigerian patient is described with megaloblastic anemia due to vitamin B12 deficiency. The deficiency resulted from malabsorption of the vitamin, but no other abnormal functioning of the gastrointestinal tract could be demonstrated. The patient did not have addisonian pernicious anemia. He had remarkable hyperpigmentation of the skin, especially of the palms of the hands. What is known of possible connections between megaloblastic anemias and melanin metabolism cannot explain this hyperpigmentation.
A Series of New Screening Procedures for Pyruvate Kinase Deficiency, Glucose-6-Phosphate Dehydrogenase Deficiency, and Glutathione Reductase Deficiency
Authors: BEUTLER ERNEST , Halasz Agnes
Published: October 2019

BEUTLER, E.: A SERIES OF NEW SCREENING PROCEDURES FOR PYRUVATE KINASE DEFICIENCY, GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY, AND GLUTATHIONE REDUCTASE DEFICIENCY. Blood 28:553-562, 1966.

In the October 1966 issue of Blood, on page 557 the concentration for GSSG was erroneously given as .003 M. The line under B. Reaction Mixture should read:

GSSG, .033M 0.1 ml.
Neutrophile Alkaline Phosphatase Changes in Tularemia, Sandfly Fever, Q Fever and Noninfectious Fevers
Authors: BEISEL WILLIAM R. , Shepel Sophie , Long Ray F.
Published: October 2019

Responses of neutrophile AP were studied in volunteers during induced tularemia, Q fever, sandfly fever, and during artificial hyperthermia and endotoxin fever. Symptoms of typical early tularemia were accompanied by a slight increase in the neutrophile count and AP index. The latter continued to rise slowly and eventually became maximal 5 days after the height of clinical illness, long after fever and leukocytosis had disappeared. Similar but less obvious changes occurred after mild tularemia and after typical early Q fever. A transient rise of neutrophile AP occurred only at the onset of fever and neutropenia in sandfly fever. An early fall in neutrophile AP after endotoxin administration was confirmed; this was followed in turn by a prolonged rise not described heretofore. Despite the stress and leukocytosis of environmentally induced artificial hyperthermia, leukocyte AP did not increase.

Based upon these observations it seemed evident that increased leukocyte AP activity could not be correlated in all circumstances with fever per se, the appearance of band cells, or the magnitude or timing of "stress" as inferred from increased plasma and urinary steroids. Increased neutrophile AP activity in these infections did not seem to be related directly to glucocorticoid excess. Possible factors involved in the induction of neutrophile AP may include the genetic potential of various cell types, coenzyme requirements, hormonal responses, as well as other yet unknown factors associated with acute infection.
Regulatory Mechanisms in the Human Leukocyte
Authors: SILBER ROBERT
Published: October 2019

The feedback control of dCMP deaminase, the first enzyme in a biosynthetic sequence of pyrimidine deoxyribonucleotide interconversions, has been characterized in leukocytes isolated from the peripheral blood of normal subjects and from patients with leukemia. As reported in other systems, dTTP, an end product of the pathway, may function as an allosteric inhibitor of this enzyme, while dCTP, another end product, prevents the dTTP inhibition.

Nucleoside deaminase is present in human leukocytes. Some of its properties are described.
APLASTIC ANEMIA
Authors: FITZPATRICK WILLIAM J. , SCHWARTZ STEVEN O.
Published: October 2019

Two cases of aplastic anemia following gold therapy are presented, bringing the total number of reported cases to 20. In one of the cases BAL was unsuccessfully used therapeutically.
ERYTHROBLASTOSIS FETALIS IN NEGROID INFANTS
Authors: WIENER A. S. , WEXLER I. B.
Published: October 2019

Three cases of Negroid infants with clinical signs and symptoms resembling erythroblastosis fetalis were presented. In none of the cases was there any evidence of Rh sensitization. Two of the cases were apparently due to sensitization of the mother to the B agglutinogen; in the third case no serologic incompatibility could be demonstrated. The possible significance of these observations was discussed.
A STUDY OF SICKLING OF YOUNG ERYTHROCYTES IN SICKLE CELL ANEMIA
Authors: WATSON JANET
Published: October 2019

1. Data have been presented to show that most reticulocytes from patients with the sickle cell trait or sickle cell anemia sickle as readily as do more mature red blood cells. The most immature reticulocytes and normoblasts tend to sickle more slowly.

2. Orthochromatic normoblasts were the only type of normoblasts which sickled; the basophilic and polychromatophilic types could not be sickled.

3. It is suggested that the sickle cell forms seen in ordinary stained smears represent old cells which have lost their "elasticity" while stagnating in the sickle shape, and are unable to revert to a biconcave disk. This would explain the fact that these forms are so rarely found to be reticulated when stained with brilliant cresyl blue.
Brief Report: The Isolation of Cytomegalovirus from Peripheral Blood
Authors: HARNDEN D. G. , ELSDALE T. R. , YOUNG D. E. , ROSS A.
Published: October 2019

Cytomegalovirus was isolated on two separate occasions from the washed leukocyte fraction of the peripheral blood of an 8-year-old boy with acute lymphatic leukemia. The child, who was treated, showed no other evidence of CMV infection. The relationship between CMV infection and leukemia is discussed.
Recurrent Ecchymoses and Cutaneous Hyperreactivity to Hemoglobin: A Form of Autoerythrocyte Sensitization
Authors: KREMER WILLIAM B. , MENGEL CHARLES E. , NOWLIN JOHN B. , NAGAYA HIROSHI
Published: October 2019

A patient with recurrent painful ecchymoses was presented with features similar to those described for patients with autoerythrocyte sensitization. This patient differed in that she was reactive to the red cell hemolysate and purified hemoglobin and not to red cell lipid, red cell stroma, or leukocyte DNA. No evidence was found to support the hypothesis that the abnormal vascular reaction involved an immunologic mechanism. The patient was observed forcibly inducing bruises but not manipulating the skin tests. It was concluded that a cutaneous hyperreactivity to hemoglobin in association with psychological disturbances was responsible for the painful ecchymoses in this patient.
Melphalan in Multiple Myeloma
Authors: HOOGSTRATEN BARTH , SHEEHE PAUL R. , CUTTNER JANET , COOPER TALBERT , KYLE ROBERT A. , OBERFIELD RICHARD A. , TOWNSEND STUART R. , HARLEY JOHN B. , HAYES DONALD M. , COSTA GIOVANNI , HOLLAND JAMES F.
Published: October 2019

1. A group of 64 myeloma patients was given a loading dose of Melphalan, 0.15 mg./Kg./Dx7. This was followed by a rest period to allow bone marrow recovery to occur, after which maintenance therapy with a maximum of 0.05 mg./Kg./D was started.

2. To obtain good results, drug doses were required which produced significant bone marrow depression.

3. Subjective improvement was noticed in about 65 per cent of patients; objective improvement, in 78 per cent.

4. Fifty-five per cent of the patients had a response as defined in this study.

5. No difference in survival was found between males and females, nor between patients with Bence Jones proteinuria and those without.

6. Patients who have been on treatment for 3 months and were then found to be responders lived longer than similarly treated patients classified as nonresponders.
Paroxysmal Nocturnal Hemoglobinuria
Authors: BLUM STUART F. , GARDNER FRANK H. , Paci Dominica
Published: October 2019

1. Crude bovine thrombin contains most, if not all, the proteins of bovine serum.

2. The effect of crude bovine thrombin in enhancing the lysis of paroxysmal nocturnal hemoglobinuria erythrocytes has been shown to be an effect on the erythrocytes themselves.

3. By enzyme inactivation, absorption technics and Sephadex chromatography the thrombic clotting activity has been separated from the PNH enhancing activity nullifying any role of thrombic clotting activity in the enhancement of PNH hemolysis by crude bovine thrombin.
Inhibition of Mitosis by Chloramphenicol in Phytohemagglutinin Stimulated Lymphocytes
Authors: PISCIOTTA ANTHONY V. , DEPREY CECELIA
Published: October 2019

1. When lymphocytes from human peripheral blood are treated with phytohemagglutinin, they undergo transformation to blast cells and then divide.

2. When chloramphenicol was added to the culture at the beginning of the experiment, mitosis was delayed but blast transformation was not affected.

3. CAP suppressed mitosis less markedly when added to the culture at 24 and 48 hours and more markedly when added daily.

4. Mitotic index was suppressed in two patients who had aplastic anemia due to CAP, in a manner similar to that observed in presumably normal people.

5. Possible reasons for this drug effect on cell division are discussed.
Effect of Antibody Binding and Agglutination on Human Platelet Glycolysis: Comparison with Thrombin and Epinephrine
Authors: KARPATKIN SIMON , SISKIND GREGORY W.
Published: October 2019

Freshly collected human platelets were washed in a modified human Ringer solution, pH 7.1, and aerobically incubated in the same media for 1 hour in the presence or absence of glucose. The effect of rabbit antihuman platelet antibody or univalent rabbit antihuman platelet antibody fragments (Fab) on platelet glycolysis was determined. Although ATP expenditure and glycogenolytic depletion were noted following platelet agglutination by antibody, these changes were not considered to be of major importance in the in vivo destruction of platelets. Univalent fragments were shown to bind to platelets without causing platelet agglutination or any detectable change in the glycolytic parameters. In contrast, intact platelet antibody resulted in platelet agglutination which was associated with an increase in lactate production and a decrease in ATP levels when platelets were incubated in the absence of glucose. Glucose-6-P levels did not change. When platelets were incubated in the presence of glucose, glucose uptake increased, ATP levels declined and glucose-6-P levels were unchanged. However, the increased glucose uptake was not accompanied by a parallel increase in lactate production as in the case with thrombin or epinephrine-induced agglutination of platelets. It is postulated that platelet antibody activates a glucose-requiring nonglycolytic pathway, perhaps the hexosemonophosphate shunt or the Krebs’ cycle.
Lymphocyte and Granulocyte Enzyme Activity in Patients with Down’s Syndrome
Authors: NADLER HENRY L. , MONTELEONE PATRICIA L. , INOUYE TOHRU , HSIA DAVID YI-YUNG
Published: October 2019

Patients with trisomic Down’s syndrome were found to have significant increases of acid phosphatase, alkaline phosphatase, and glucose-6-phosphate dehydrogenase in both lymphocytes and polymorphonuclear leukocytes separated from white blood cells by the procedure of Rabinowitz. The alteration in enzyme activities appears not to be directly related to genes located on the chromosome causing Down’s syndrome.
Melphalan Therapy for Plasma Cell Myeloma
Authors: ALEXANIAN RAYMOND , BERGSAGEL DANIEL E. , MIGLIORE PHILIP J. , VAUGHN WILLIAM K. , HOWE CLIFTON D.
Published: October 2019

Of 82 patients with plasma cell myeloma treated with melphalan, 40 (49 per cent) were improved in clinical status and in a direct manifestation of disease. Myeloma protein level provided an important parameter for periodic assessment of disease activity. After effective chemotherapy, myeloma globulins decreased more rapidly and to a greater degree in urine than in serum. Anemia and hypoalbuminemia were improved in most responding patients, thus supporting the usefulness of these parameters in confirming clinical response. Median survival time for all patients was 42 months from symptoms, 34 months from diagnosis, and 23 months from melphalan. The life-span of responding patients was prolonged more than 2 years, a period accounted for by the duration of objective response. Future progress in treatment for plasma cell myeloma will depend more on advances in chemotherapy than upon improvements in supportive care.
Chronic Myelocytic Leukemia in Identical Twins and a Sibling
Authors: TOKUHATA GEORGE K. , NEELY CHARLES L. , WILLIAMS DOROTHY L.
Published: October 2019

Identical twins and their older brother have been studied: all diagnosed within a span of three months as having chronic myelocytic leukemia; both twins were symptomatic and the brother asymptomatic. Chromosome analyses were made on peripheral blood cells. The asymptomatic brother had never been treated. The Ph1 chromosome was present in each of the three siblings.

A number of other chromosome abnormalities were found. Results were interpreted in terms of a probable genetic factor in the Philadelphia chromosome and susceptibility to chronic myelocytic leukemia.
Erythropoietin Inhibitor in Kidney Extracts and Plasma from Anemic Uremic Human Subjects
Authors: FISHER JAMES W. , HATCH F. E. , ROH B. L. , ALLEN R. C. , KELLEY B. J.
Published: October 2019

1. An erythropoietin inhibitor has been demonstrated in human kidney homogenates from two patients with chronic renal insufficiency and two normal human subjects. The level of the inhibitor was significantly higher in the nephritic kidney homogenates than that of the normal kidneys. The ESF inhibitor was found in the soluble cytoplasmic fraction of the kidney, using an osmotic sucrose gradient and differential centrifugation technic. The inhibitor was still present after in vitro dialysis of the kidney soluble fractions and was partially inactivated by boiling.

2. The nuclear and mitochondrial fractions from the normal and nephritic kidneys markedly accentuated the erythropoietic activity of human urinary ESF when injected simultaneously at separate sites in polycythemic mice. The accentuating effects on ESF of the above fractions was significantly less in the nephritic than in the normal kidneys.

3. Flat bed discontinuous acrylamide gel electrophoresis studies on the kidney homogenates revealed a marked increase in the concentration of protein and a decrease in esterase activity in the albumin fractions in the nephritic kidney when compared with those of the normal kidneys. An additional band between the albumin and alpha-1-globulin regions was detected in the nephritic kidney fractions which was not present in the normal kidney fractions. The significance of these observations as they may relate to the inhibitor is discussed.

4. Plasma from five out of six anemic uremic subjects produced a significant inhibition of ESF; while normal human plasma was found to accentuate the erythropoietic effects of ESF.

5. A marked enhancement of the erythropoietic effects of human urinary ESF by human liver homogenate was also seen.

6. It is postulated from these studies that the anemia of chronic renal insufficiency is due, at least in part, to erythroid failure resulting from a lack of available erythropoietin. This deficiency in erythropoietin activity is probably due to an increase in an ESF inhibitor and/or a decrease in a renal erythropoietic factor (REF).
Inhibition of Sulfhydryl-Dependent Platelet Functions by Penetrating and Non-Penetrating Anologues of Parachloromercuribenzene
Authors: ALEDORT LOUIS M. , TROUP STANLEY B. , WEED ROBERT I. , Santillo Patricia
Published: October 2019

The effects of PCMB and PCMBS on cation permeability, ADP aggregation, platelet volume and clot retraction have been studied in intact human platelets and have been compared to the effects of ouabain on the same functions. The influence of these agents on Mg+ + -dependent ATPase activity and Na+, K+ activated ATPase activity of osmotically lysed platelets also has been evaluated. (a) Ouabain, which produces inhibition of Na-, K+ dependent ATPase activity, has no influence on ADP-induced aggregation or clot retraction. (b) Both PCMB and PCMBS inhibit all ATPase activities in osmotically lysed platelets and inhibit ADP aggregation by intact platelets. Cysteine reverses the inhibition of ADP aggregation produced by both PCMB and PCMBS at a time when PCMB induced inhibition of clot retraction no longer is reversible. (c) Clot retraction is inhibited by the penetrating agent, PCMB, but is not affected by identical concentrations of PCMBS. These observations suggest that ADP aggregation and clot retraction are independent phenomena.
Brief Report: Rapid Determination of Vitamin Bl2-Binding α and β 3 Globulin in Serum
Authors: SILVERSTEIN ELLEN , HERBERT VICTOR
Published: October 2019

A procedure has been described for the rapid and separate measurement of B12-binding α- and β-globulins using the batch technic. The method involves saturating B12-binders with Co57B12, removing excess radioactive B12 with a hemoglobin-coated charcoal pellet, and then separating the B12 binders using a pellet of DEAE cellulose, from which only the β-globulins are eluted in 0.06 M phosphate buffer at pH 6.35.
Immunoglobulin Abnormalities in Gaucher’s Disease Report of 16 Cases
Authors: PRATT PETER W. , ESTREN SOLOMON , KOCHWA SHAUL
Published: October 2019

Sera from ten of sixteen patients with known Gaucher’s disease were found to have immunoglobulin abnormalities. Of these, four patients had "monoclonal" IgG type K protein increases. The possible pathogenic roles of lipid accumulation and reticuloendothelial hyperplasia are discussed.
Splenic Erythroclasia: An Electron Microscopic Study of Hemoglobin H Disease
Authors: WENNBERG EMMA , WEISS LEON
Published: October 2019

This is an electron microscopic study of the spleen in a case of hemoglobin H disease. The patient showed evidence in the peripheral blood of marked erythrocyte fragmentation.

The spleen acted upon the abnormal erythrocytes in two major ways:

1. The erythrocytes entered the sinus lumen simultaneously via two intercellular slits on opposite sides of a lining cell and then split into two sphered fragments (which lay free in the sinus lumen) and the long, thin connecting fragment (which was retained in the cordal compartment and phagocytized).

2. Small, dense, spherical portions of erythrocytes were retained in the cord while the major portion of the cell was released into the sinus lumen. This is suggestive of pitting of rigid intracellular precipitates.

The erythrocytes emerged from their passage through the cords and maintained bizarre forms in the sinus lumen. It is possible that the contents of these cells may be partially gelated to account for this.11 This gelation is thought to largely underlie their behavior in their circulation through the spleen. Evidence of increased erythrocytic breakdown was found in the numerous large macrophages present in the cords.
The Use of 32Di-Isopropylfluorophosphate (32DFP) As A Platelet Label: Evidence for Reutilization of This Isotope In Man
Authors: COONEY D. P. , SMITH B. A. , FAWLEY D. E.
Published: October 2019

Certain aspects of 32DFP metabolism in man have been studied. It is probable that about 10 per cent of an injected dose is metabolized and reappears in the platelet. This affects the platelet decay curve after day 8 and may influence data on red and white cell kinetics obtained with this isotope.

Considering the effects of reincorporation of this compound, we have studied twenty normal individuals and have found a mean platelet lifespan of 11.5 days. Statistical analysis supports the concept that the platelet decay curve is linear: platelets are removed from the circulation because of senescence rather than in a random fashion.

The literature on human platelet lifespans is reviewed. Most authors support the concept of a linear decay curve, although the evidence is conflicting and opinions are divided.
Acquired von Willebrand’s Syndrome in Systemic Lupus Erythematosus
Authors: SIMONE JOSEPH V. , CORNET JO ANN , ABILDGAARD CHARLES F.
Published: October 2019

A boy is described with clinical and laboratory manifestations which were indistinguishable from von Willebrand’s disease. However, the relatively recent onset of symptoms, the negative family history, and the normal coagulation studies in both parents and six siblings led to the belief that the bleeding syndrome was acquired rather than inherited. The patient subsequently developed systemic lupus erythematosus following a smallpox vaccination. The findings of von Willebrand’s syndrome disappeared following corticosteroid therapy and did not return after cessation of therapy.
Subcellular Distribution of Human Leukocytic Cathepsins
Authors: STILES MARY ANN , FRAENKEL-CONRAT JANE
Published: October 2019

1. Methods are presented for the disruption of human peripheral leukocytes by sonication and the separation of the released particulate matter by differential centrifugation.

2. The distribution of catheptic activity in the various fractions was investigated both on material obtained from mixed populations of leukocytes and on that from isolated lymphocytes and granulocytes.

3. All of the leukocytic fractions tested contained cathepsins active at pH 3.5 and pH 8.5.

4. At pH 3.5, the catheptic activity was rather evenly distributed among nuclear (I), and light (IV) and heavy (II) granular fractions, with practically no activity in the soluble fraction (V).

5. At pH 8.5, there was always more catheptic activity in the heavier (II) than the lighter (IV) granules, variable amounts in the nuclear fraction (I) and very little in the supernatant (V).

6. At pH 3.5, the lymphocytic granules showed considerably higher proteolytic specific activity than those from granulocytes.

7. At pH 8.5, all fractions except the heavy granules (II) had higher proteolytic specific activities in granulocytes than in lymphocytes.

8. At pH 3.5, and to a lesser extent at pH 8.5, the light (IV) and heavy (II) granules from chronic lymphatic leukemia cells contained much lower cathepic activity than those from normal lymphocytes.

9. Cathepsins in each subcellular fraction are very labile, losing as much as 80 per cent of their activity upon storage at 4 C. overnight in distilled water.
Hemolytic Anemia Associated with Low Erythrocyte ATP
Authors: MILLS GORDON C. , LEVIN WILLIAM C. , ALPERIN JACK B.
Published: October 2019

Studies have been carried out on erythrocytes of a young girl with a severe hemolytic anemia. Biochemically, these cells were characterized by a very high glycolytic rate, a low ATP level, an elevated ADP:ATP ratio, and a markedly increased rate of catabolism of adenine nucleotides to hypoxanthine during incubation in vitro.

Specific enzyme assays of the patient’s cells revealed normal or elevated values for glucose-6-phosphate dehydrogenase, pyruvate kinase, glutathione reductase, enolase, adenosine triphosphatase, and adenine phosphoribosyl transferase.

In in vitro incubation studies, addition of adenine to the blood brought about an increase in the ATP level and in total adenine nucleotides. These data suggest that the low ATP level in the patient’s blood was due to increased catabolism of adenine nucleotides, probably as a consequence of markedly increased utilization of ATP by the cell.
Phagocytosis by Human Monocytes
Authors: CLINE MARTIN J. , LEHRER ROBERT I.
Published: October 2019

Human monocytes isolated from peripheral blood phagocytized polystyrene particles, Escherichia coli, Staphylococcus aureus, Candida albicans, Cryptococcus neoformans, and red cells coated with IgG antibody in vitro. The ingestion of fungi and bacteria required serum or serum fractions. Ingestion of antibody-coated erythrocytes was inhibited by whole serum or IgG, but not by IgM or albumin. Adherence to a surface appeared to be critical for erythrophagocytosis but not for ingestion of bacteria.

Phagocytosis occurred over a broad pH range and in the presence of inhibitors of oxidative metabolism and of RNA synthesis. Phagocytosis was significantly depressed by inhibitors of glycolysis (iodoacetate and fluoride) and by chloroquine at 1 x 10-5M. Particle ingestion by monocytes was accompanied by enhanced production of C14O2 from glucose-1-C14, but was not associated with a detectable increase in total glucose utilization, incorporation of radioactive uridine into RNA, or incorporation of amino acids into protein.
Immunosuppression by Cyclophosphamide in NZB X NZW Mice With Lupus Nephritis
Authors: CASEY T. P.
Published: October 2019

Long-term administration of cyclophosphamide to groups of young and old NZB X NZW hybrid mice in controlled therapeutic trials showed:

1. decreased antinuclear autoantibody production as judged by LE cell and latex nucleoprotein tests,

2. marked benefit to lupus nephritis lesions, and

3. no carcinogenic effects.

Attention is drawn to the prospect of using these mice to study the carcinogenic effects of antimitotic drugs with particular reference to the effects of such drugs on immune mechanisms.
Allopurinol and Iron Metabolism in Man
Authors: BOYETT JOHN D. , VOGLER WILLIAM R. , FURTADO VALDIR DE PAULA , SCHMIDT FREDERICK H.
Published: October 2019

Oral and intravenous ferrokinetic studies were carried out in 9 patients with gout or hyperuricemia to determine the effect of allopurinol on iron absorption, storage, and red cell incorporation. Two studies were carried out in each patient: one during the control period and the other while receiving allopurinol. Allopurinol had no measurable effect on iron metabolism.
Arabinosyl Cytosine: A Useful Agent in the Treatment of Acute Leukemia in Adults
Authors: ELLISON ROSE RUTH , HOLLAND JAMES F. , WEIL MARISE , JACQUILLAT CLAUDE , BOIRON MICHEL , BERNARD JEAN , SAWITSKY ARTHUR , ROSNER FRED , GUSSOFF BERNARD , SILVER RICHARD T. , KARANAS ARTHUR , CUTTNER JANET , SPURR CHARLES L. , HAYES DONALD M. , BLOM JOHANNES , LEONE LOUIS A. , HAURANI FARID , KYLE ROBERT , HUTCHINSON J. L. , FORCIER R. JACKSON , MOON JOHN H.
Published: October 2019

Arabinosyl cytosine (ara-C), a synthetic pyrimidine nucleoside related to the normal metabolites cytidine and deoxycytidine, has been found capable of producing marrow remission at tolerable doses in acute myelocytic and acute lymphocytic leukemia in adults. There were 16 per cent remissions complete in all aspects, 3 per cent complete except for hemoglobin level, and 6 per cent partial remissions among 180 adults with acute myelocytic leukemia treated with any one of 8 variants of infusion duration or daily dose of ara-C. Twenty-four per cent of 37 adults with acute lymphocytic or unclassified leukemia had complete or partial remissions. The comparison of 1, 4, 12 and 24 hours infusion of ara-C (to total dose tolerated) does not show significant superiority for any one group. The complete remission rate with 1 or 12 hour infusions, however, is 25 per cent (superior to that obtained with 6-mercaptopurine) and the recommended schedule of treatment for ara-C based on these data is, therefore, daily infusions of 100 or 50 mg./m.2 in one hour for approximately 3 to 6 weeks followed by maintenance therapy of once weekly subcutaneous injection of 30 mg./m.2 of ara-C. Platelet transfusions should be available when ara-C is used.
Serum Antibodies Against Desipramine as a Possible Cause for Thrombocytopenia
Authors: RACHMILEWITZ ELIEZER A. , DAWSON R. BEN , RACHMILEWITZ BRACHA
Published: October 2019

In vitro tests were done on the serum and platelets of two patients who had thrombocytopenia while taking desipramine (Pertofrane®), the active metabolite of imipramine (Tofranil®).

The indirect agglutination test with barium sulfate demonstrated the presence of antibodies against desipramine (titer of 1:256). Follow-up studies showed decreasing antibody titers in both patients after discontinuation of the drug. By complete inhibition of clot retraction and by platelet agglutination, the platelets were shown to be involved in the antigen-antibody reaction.

The antibodies against desipramine were characterized as 7S-IgG types for both patients. The characterization of antibodies may prove to be a useful step in clarifying the mechanisms involved in drug-induced blood dyscrasias.
The Substructure of Human Platelet Microtubules
Authors: WHITE JAMES G.
Published: October 2019

The substructure of the marginal bundle of microtubules supporting the discoid shape of platelets has been examined in negatively stained cells. Platelets were swollen first by exposure to distilled water, spread by surface tension, and mounted on carbon stabilized formvar coated grids. The findings differ from the work of previous investigators in the following ways:

1. Usually one microtubule remains in the circumferential bundle after pretreatment with distilled water.

2. The microtubules are composed of 12-15 subfilaments in parallel association. Each subfilament is composed of beads stacked in such a manner as to suggest a helical wind.

3. A diagonal pattern with a periodicity of 40 A° cuts across the long axis of the parallel subfilaments. This pattern suggests that globular subunits are 35-40 A° by 40 A° in size, and that beads on adjacent subfilaments are not in exact parallel register. Thus, the entire microtubule appears to be composed of subfilaments associated in a helical array.

4. At sites of partial fracture in microtubules, subfilaments lose their parallel association and spray out as free elements. The free subfilaments are essentially identical in appearance to hyaloplasmic microfilaments.

The relationship between subfilaments of microtubules, hyaloplasmic microfilaments, and the contractile mechanism of the platelet is discussed.