bluuebunny/crossref_metadata_2025 huggingface dataset:
Ferritin Localization on the Erythroblast Cell Membrane and Ropheocytosis in Hypersiderotic Human Bone Marrows
Authors: TANAKA YASUKAZU , BRECHER GEORGE , BULL BRIAN
Published: October 2019

1. Preferential ferritin localization on specialized areas of the plasma membrane of erythroblasts with subsequent invagination into ropheocytotic vesicles, and the occurrence of ropheocytosis without ferritin being present in the vesicles, has been previously described.

2. In a study of bone marrows from patients with hypersiderosis we have confirmed the previous observations, but we frequently found nonferritin ropheocytosis in erythroblasts adjacent to ferritin laden reticulum cells. In addition, ferritin localization along the outer surface of erythroblasts was noted, particularly between continuous surfaces of two adjacent erythroblasts. Such intercellular accumulations of ferritin were not necessarily associated with a high ferritin content of adjacent cells.

3. These observations did not favor the hypothesis that ferritin iron was being transferred directly from reticulum cells to adjacent erythroblasts. It is suggested that the accumulation of ferritin along extended stretches of the erythroblast surface may signify that iron which is detached from siderophilin but not immediately transported across the cell membrane is incorporated into apoferritin produced on the cell membrane.
A Study of Histamine in Myeloproliferative Disease
Authors: GILBERT HARRIET S. , WARNER RICHARD R. P. , WASSERMAN LOUIS R.
Published: October 2019

1. Whole blood histamine content was measured in 80 patients with myeloproliferative disease. Increased levels were found in 60 per cent of patients with uncontrolled polycythemia vera, in 7 per cent of patients with polycythemia vera being controlled by myelosuppressive therapy, and in 71 per cent of a group with "spent" polycythemia, myeloid metaplasia and myelofibrosis.

2. The excretion of histamine in the urine was measured in 60 patients, 30 with elevated blood histamine and 30 with normal blood histamine. The urine findings paralleled the blood findings in 90 per cent of the cases.

3. Measurements of cell-poor and cell-rich fractions of blood showed that the histamine is contained in the white cell fraction. Elevated basophil counts were present in 50 per cent of the patients and occurred with the greatest frequency in the groups with elevated blood and urine histamine. A rough correlation between the basophil count and the histamine content of blood and white cell fractions was observed in normal subjects and most cases with myeloproliferative disease. Data obtained in some cases of myeloproliferative disease suggest that the histamine content of the basophil may be abnormal and that other granulocytes may contribute to the total leukocyte histamine.

4. Myelosuppressive agents produced a reduction in histamine (expressed per 109 myeloid cells) and a decrease in urine histamine as control of the myeloproliferative process was achieved. Treatment with phlebotomy alone produced no change in histamine levels.

5. The incidence of pruritus, upper gastrointestinal distress and urticarial manifestations was increased 7-fold, 4-fold and 12-fold, respectively, in patients with elevated histamine levels as compared with those who had normal histamine levels.

6. Cyproheptadine, a potent antihistaminic, successfully controlled pruritus, relieved pyrosis and suppressed urticarial eruptions in patients with elevated histamine levels. Suppression of the reaction to subcutaneously administered codeine (a histamine-releaser) afforded objective evidence that cyproheptadine blocked the effects of histamine release in vivo.

7. The metabolism of histamine and the role of elevated histamine levels in the clinical manifestations and pathophysiology of myeloproliferative disease are discussed.
Brief Note: Tritiated Thymidine as a Cytocidal Agent in Human Leukemia
Authors: GREENBERG MICHAEL L. , CHANANA ARJUN D. , CRONKITE EUGENE P. , SCHIFFER LEWIS M. , STRYCKMANS PIERRE A.
Published: October 2019

1. Two patients with acute leukemia had considerable decreases in leukemic cells in the peripheral blood as well as reduction in size of spleen and leukemic masses after 10 injections of 3H-TDR given over a 5-day period. Each injection was 0.25 µc./Gm. body weight.

2. The pertinent aspects of cytotoxic effects of 3H-TDR are reviewed.

3. The radiation doses delivered to the nucleus are estimated from autoradiographic data.

4. Evidence is presented for the observed effects being due to 3H-TDR.
The Lactate Dehydrogenases of Hemopoietic Cells
Authors: STARKWEATHER W. H. , SPENCER H. H. , SCHOCH H. K.
Published: October 2019

In summary we have demonstrated that hemopoietic stem cells of man contain all five isoenzymes, and not a single pure type. Our data and the results of others obtained from fetal tissue also indicate that embryonic LDH of man exists as multiple forms. We have demonstrated that differentiation, with respect to LDH isoenzymes, of stem cells along erythrocytic, granulocytic, and lymphocytic lines, occurs in different sequences. It appears that LDH-1 synthesis is necessary in mitotic granulocytic cells, but ceases at the metamyelocyte level where LDH-5 synthesis begins. LDH-5 synthesis occurs in early erythroid cells and probably ceases at the reticulocyte level.27 This is not accompanied by stimulation of LDH-1 synthesis. The maturation of lymphocytes is characterized by a stimulation of LDH-5 synthesis, which is not diminished in the normal circulating cell. Lymphocytes obtained from normal individuals and cultured in vitro in the presence of phytohemagglutinin demonstrate reversion of LDH patterns to those seen in acute leukemias. Our data further indicate that the isoenzyme pattern obtained from hemopoietic cells are indicative of the degree of cellular differentiation, and substantiate the concept of a defective differentiation and maturation process in acute leukemic cells.
The Influence of Hypoxemia and Cobalt on Erythropoietin Production in the Isolated Perfused Dog Kidney
Authors: FISHER JAMES W. , LANGSTON J. W.
Published: October 2019

Isolated dog kidneys were perfused with blood at normal and reduced oxygen tensions with and without cobalt. Erythropoietin titers were found to be significantly increased in the blood perfusates from kidneys perfused with blood at lowered oxygen tensions, while no change in erythropoietin was seen when kidneys were perfused with blood at a normal oxygen tension. Cobalt produced significant increases in erythropoietin levels in the perfusates with normal as well as reduced oxygen tension blood, but its effect was more marked when the kidneys were perfused with hypoxic blood. Renal blood flows were higher when the dogs’ own lungs were used to oxygenate the blood than when a bubble oxygenator was used in the system. However, hypoxic blood resulted in significant increases in erythropoietin production in both systems. In studies of the kidney histology from both perfusion systems with hypoxic and normal oxygen tension blood, most of the kidneys demonstrated varying degrees of glomerular congestion. No correlation was found between erythropoietin elaboration and renal congestion or other degenerative cellular changes in the kidney. Therefore, it does not seem likely that erythropoietin produced in the isolated perfused kidney is due to histologic damage to renal cells. These findings support the concept that increased erythropoietin production in the isolated perfused kidney in response to cobalt or hypoxic blood is a direct effect of these stimuli on the kidney.
RNA Metabolism of Normal and Leukemic Leukocytes
Authors: SILBER ROBERT , UNGER KENNETH W. , KELLER JOAN , BERTINO JOSEPH R.
Published: October 2019

Ribonuclease has been partially purified from human leukocytes and its properties investigated. The enzyme has a pH optimum between 6 and 6.5. It is equally active with RNA prepared from various sources, attacking phosphodiester bonds adjacent to pyrimidine bases. Activity in myeloblasts or lymphocytes is about one-tenth that of mature granulocytes.
Malic and Lactic Dehydrogenase Isozymes of Normal and Leukemic Leukocytes Separated on Glass Bead Columns
Authors: RABINOWITZ YALE , DIETZ ALBERT A. , Wilhite Betty A. , Lubrano Tina
Published: October 2019

Five LDH and two MDH isozyme bands were obtained with acrylamide gel electrophoresis of leukocyte extracts. Normal lymphocytes showed a high total H-LDH (heart type) activity (67 per cent) with 25 per cent in LDH-1 and only 3.5 per cent in LDH-5. Lymphocytes from chronic lymphatic leukemia (CLL) and lymphosarcoma leukemia (LSA-LL) had less LDH-1, and more LDH-3 and LDH-4, than normal lymphocytes. The H-LDH fell to 60.5 per cent in CLL and 56 per cent in LSA-LL. PMN leukocytes had low H-LDH activity (38.8 per cent) with 3.3 per cent in LDH-1 and 25.8 per cent in LDH-5. In myelogenous leukemia, myeloblasts had the most LDH-1 and H-LDH, while mature PMN had the least. PMN leukocytes isolated from CLL, LSA-LL, and myelogenous leukemia had LDH patterns like the normal. Monocytes from acute monocytic leukemia were low in LDH-1 and LDH-5, but had a high total enzyme content. They evidently were rich in LDH-2, 3, and 4.

Lymphocytes had less MDH-1 (60 per cent) than PMN leukocytes (78 per cent). In CLL, lymphocyte MDH-2 increased. In myelogenous leukemia, myeloblasts had the most MDH-2 and mature PMN the least. Monocytes from monocytic leukemia contained a little more MDH-2 than PMN leukocytes.

In general, white cell immaturity and/or ability to divide was associated with high levels of LDH-1, total H-LDH, and MDH-2.
Hematologic Effects of Splenic Implants
Authors: TARNUZI ACHMAD , SMILEY R. KENNEDY
Published: October 2019

1. Splenectomy in the rat results in a marked elevation in the number of circulating leukocytes and platelets.

2. Transient suppression of the leukocytosis may result from the presence of a 10 per cent splenic implant, either free in the peritoneal cavity or enclosed in a Millipore diffusion chamber.

3. Marked and persistent suppression of postsplenectomy thrombocytosis results from the presence of a 10 per cent splenic implant, whether free or enclosed in a 0.45 µ Millipore diffusion chamber.

4. The results provide indirect evidence of a humoral substance produced by rat spleen which influences platelet levels; presumably this substance acts by suppressing thrombopoiesis.
Cyclic Neutropenia in Grey Collie Dogs
Authors: LUND JOHN E. , PADGETT GEORGE A. , OTT RICHARD L.
Published: October 2019

Cyclic neutropenia in a grey collie dog was first diagnosed at 10 weeks of age and has persisted 12 months. The average cycle length was 10.6 days with a range of 8 to 12 days. The condition was found in 2 other dogs of the type described and appears to be inherited along with a grey (silver) coat. The peripheral neutropenia results from a cyclic maturation arrest in the bone marrow at the level of differentiation from the stem cell.
In Vitro Development of Bone Marrows from Patients with Neutropenia
Authors: LAU PETER , BRODY JEROME I. , BEIZER LAWRENCE H.
Published: October 2019

Bone marrows from patients with neutropenia, characterized morphologically by a paucity of mature neutrophils, underwent normal maturation when removed from the body and grown in tissue culture. In addition, certain leukopenic plasmas appeared to stimulate development of normal bone marrows under similar circumstances. These observations suggest that the granulocytic elements in benign forms of neutropenia are innately capable of normal sequential growth and that sustained peripheral neutropenia may distort the normal feedback mechanism which regulates leukopoiesis.
Special Article: Chronic Lymphocytic Leukemia—an Accumulative Disease of Immunologically Incompetent Lymphocytes
Authors: DAMESHEK WILLIAM
Published: October 2019

Chronic lymphocytic leukemia, far from being simply a very chronic, very dull disease, has many facets which may help to illuminate the pathogenesis of a variety of immunologic aberrations. It appears likely that this is an accumulative disease of lymphocytes rather than one which is due to rapid proliferation, as was originally thought. The abnormal lymphocytes of the disease—with their various indications of metabolic but, more particularly, immunologic incompetency and their reduced ability to transform with both PNA and antigenic stimulation—eventually accumulate in large masses throughout the body. In the course of time, a host of disorders develop, including reduced immunity of both humoral and cellular varieties, autoimmunity, and extreme reactions to viruses and insects, numerous infections and wasting, finally leading to death. A striking response to corticosteroids is characteristic of the disease. On the other hand, large doses of x-ray or alkylating agents may result in violent and often fatal autoimmune reactions. Many future studies are indicated to demonstrate the nature of the metabolic defect in the lymphocyte and its pathogenesis, whether genetic or on some other basis. The possibility of modifying the tendency of the abnormal lymphocyte to accumulate, perhaps with the judicious use of corticosteroids, in association with other methods deserves intensive study.
Comparative Response of Normal Human Thymus and Lymph Node Cells to Phytohemagglutinin in Culture
Authors: WINKELSTEIN ALAN , CRADDOCK CHARLES G.
Published: October 2019

Human thymocytes, in short-term tissue culture, show a proliferative activity distinct from that observed by either lymph node or blood lymphocytes. As expected, the behavior of lymph node lymphocytes in culture is very similar to that of peripheral blood lymphocytes. The only difference between these 2 groups of cells was the finding of spontaneous proliferation by normal lymph node cells after 3 days in culture without phytohemagglutinin (PHA).

Whereas blood and lymph node lymphocytes show a negligible uptake of H3T in the basal state, approximately 10 per cent of thymus cells incorporate H3T, indicating significant autonomous proliferation. This is unaffected by PHA and is unassociated with globulin synthesis as judged by immunofluorescent technics. After 3 days in culture, there are significantly more transformed cells and more cells which incorporate H3T into DNA in thymus cell cultures containing PHA than in the control cultures. However, the labeling index of stimulated thymus cultures is less than either the basal rate of proliferation of thymocytes or 3-day cultures of PHA stimulated blood and lymph node lymphocytes. These observations suggest that the normal human thymus contains at least two populations of lymphoid cells: a major component which shows autonomous and unsustained proliferative activity and does not respond to PHA, and a second and probably minor cellular component which transforms and proliferates in response to PHA.
Chronic Myelocytic Leukemia with Two Philadelphia Chromosomes and Prominent Peripheral Lymphadenopathy
Authors: DUVALL CHARLES P. , CARBONE PAUL P. , BELL WILLIAM R. , WHANG JACQUELINE , TJIO J. H. , PERRY SEYMOUR
Published: October 2019

1. Three adults with CML, 2 Ph1 chromosomes, and marked peripheral lymphadenopathy are described.

2. In each instance node enlargement was thought to be due to leukemic infiltration rather than a supervenient lymphomatous process.

3. Marked adenopathy is an unfavorable prognostic sign in CML, particularly if caused by myeloblastic infiltration. Such infiltration can precede myeloblastic involvement of the peripheral blood and bone marrow.

4. Karyotype analysis and touch preparations of extramedullary tumor tissue in CML will aid in accurate diagnosis and may help to answer more basic questions regarding the pathogenesis of this malignancy.
The Demonstration of Dehydrogenases and Diaphorases in Cells of Peripheral Blood and Bone Marrow
Authors: ROZENSZAJN L. , SHOHAM DAVIDIA
Published: October 2019

Nicotinamide adenine dinucleotide-linked dehydrogenases, SDH, NADH and NADPH diaphorases were assayed with cytochemical methods in white blood cells in bone marrow cells using tetrazolium salts, Nitro-BT and MTT. In unfixed smears specific enzymatic activity was demonstrated for glucose-6-phosphate dehydrogenase, succinic dehydrogenase and NADH diaphorase. In fixed smears the activity of lactic dehydrogenase and succinic dehydrogenase was shown. The action of NADH and NADPH diaphorases was demonstrated in the fixed smears only in the presence of NADH and NADPH. Supravital methods are inadequate for demonstration of specific enzymatic activity.

Lactic dehydrogenase activity in cells was estimated in a semiquantitative way. The enzymatic action of the dehydrogenases and the diaphorases was stronger in younger cells and decreased progressively with their maturation.
The Philadelphia Chromosome and Galactose-1-Phosphate Uridyl Transferase
Authors: WANG MAY Y. F. W. , DESFORGES JANE F. , Downes Jean
Published: October 2019

Because galactose-1-phosphate uridyl transferase has been reported to be elevated in the blood of patients with mongolism (21 trisomy), assay of this enzyme in the erythrocytes and leukocytes was performed in patients with the Philadelphia chromosome. Twenty normal individuals and 16 patients with the Ph1 chromosome were studied; 15 of the latter had chronic myelogenous leukemia and 1 had an unusual myeloproliferative disorder. The mean leukocyte enzyme level in the Ph1 group was not different from that in the normal group. The mean erythrocyte enzyme level in the Ph1 group was higher than that in the normal group; this difference might have been due to a younger population of red cells in the Ph1 patients.

To interpret the results, three postulates are presented. First, the relationship between chromosome 21 and this enzyme activity may be obscured by other controlling factors. Second, the long arm of this chromosome may play no role in transferase activity. Third, there may be no reduction of genetic material in a Ph1 karyotype.
Bleeding Syndrome in a Patient with IgA Myeloma: Interaction of Protein and Connective Tissue
Authors: VIGLIANO EDWARD M. , HOROWITZ HERBERT I.
Published: October 2019

A bleeding diathesis in a case of IgA myeloma was found to be associated with at least two abnormalities in the hemostatic mechanism. Both were related to the presence of the abnormal myeloma protein and improved with plasmapheresis and with response to tryptophane mustard therapy. The first abnormality stems from interference with fibrinogen polymerization and is responsible for prolonging the clotting time, acting as an anticoagulant on addition of the patient’s serum to normal blood, and giving rise to the gelification phenomenon noted on clotting. This abnormality is partially, but not completely, corrected by calcium; it has previously been described in other patients with multiple myeloma. The second abnormality results from coating of collagen (as well as other surfaces) by the abnormal protein and causes the prolonged bleeding time and poor in vivo adhesion of platelets. This abnormality has not been previously described and appears to be partially responsible for the patient’s bleeding.
Delivery of Co57B12 to Erythrocytes from α and β Globulin of Normal, B12-Deficient, and Chronic Myeloid Leukemia Serum
Authors: RETIEF FRANCOIS P. , GOTTLIEB CHESTER W. , HERBERT VICTOR , Go Le Teng , Lee Melody , Farrelly John
Published: October 2019

In a study of Co57B12 uptake by reticulocyte-rich erythrocytes, transfer from chronic myeloid leukemia (CML) serum was less efficient than from normal serum. Decreased transfer of Co57B12 was not due to excessive transfer of endogenous B12 (which is normally elevated in CML) but was associated with an α-globulin B12-binder (isolated from "baby" DEAE columns) unable to normally deliver B12 to erythrocytes. Delayed plasma clearance of intravenously injected B12 in CML may be due to this phenomenon.

B12-deficient serum delivered slightly more added Co57B12 to erythrocytes than did normal serum, possibly due to less interference by endogenous B12. α- and β-globulin B12 binders from B12-deficient serum transferred bound Co57B12 as efficiently as did normal serum α- and β-binders; the β-binders delivered more than the α-binders. CML β-binder delivered as well as did β- binder from pernicious anemia and normal serum. These findings suggest that the α-binder of CML serum is physiologically and therefore chemically different from the α-binder in normal and pernicious anemia serum.

Reticulocyte-rich, B12-deficient erythrocytes from pernicious anemia patients took up Co57B12 less well than did B12-sufficient reticulocyte-rich erythrocytes. This may partially explain delayed plasma clearance of B12 in B12 deficiency.

Rat liver homogenate uptake of Co57B12 was much greater when B12 was transferred from normal serum than from normal gastric juice or saline. Preliminary investigations showed that both α- and β-binders from normal serum transferred B12 to liver homogenate but CML α-binder transferred poorly.
Laboratory Studies on a Family with a Father and Son Affected by Acute Leukemia
Authors: TWOMEY J. J. , LEVIN W. C. , MELNICK M. B. , TROBAUGH F. E. , ALLGOOD J. W.
Published: October 2019

A family was studied in which two members died from leukemia, two died from cancer, and two others had hereditary telangiectasia. Slight immunoglobulin abnormalities and cytogenetic mosaicisms were found among their apparently normal relatives. The neoplastic potential of these findings can only be inferred from their previous association with similar malignancies. Their occult nature is compatible with the dearth of information concerning susceptibility toward malignant diseases. An analysis of the literature indicates that a possible predisposition toward familial leukemia is directed toward malignancy in the broad sense rather than toward any specific variety. Useful information about leukemogenesis may be forthcoming from further similar studies.
IRREVERSIBLE TOXIC "INCLUSION BODY" ANEMIA
Authors: FERTMAN M. H. , DOAN CHARLES A.
Published: October 2019

1. "Inclusion bodies," distinguishable from the Howell-Jolly bodies, were observed in the red blood cells of a patient with a severe refractory fatal anemia, who had been receiving erythrol tetranitrate over a period of one year.

2. "Bodies" with similar staining characteristics were reproduced in cats with large oral doses of erythrol tetranitrate and other nitrates. These were generally accompanied by a temporary fall in the red cell count, followed by recovery upon withdrawal of the drug.
Effect of Erythropoietin on DNA Synthesis by Erythroblasts in Vitro
Authors: POWSNER EDWARD R. , BERMAN LAWRENCE
Published: October 2019

The tentative interpretations about the action of erythropoietin in vitro, based on consideration of our present studies, are (1) that erythropoietin increases heme synthesis in bone marrow cultures as a whole, and probably in individual erythroblasts as well, and (2) that erythropoietin induces DNA synthesis by erythroblasts. On the basis of these limited data we cannot make a statement about the relation between these two effects.
"A"-Antigen Variation in Pigeon Erythrocytes
Authors: HIERHOLZER JOHN C. , SCHEINBERG S. L. , HANSEN P. A.
Published: October 2019

Experiments were carried out on the nature of "A"-inagglutinable cells. The effect of x-rays on the inagglutinable cell frequency was determined in pigeons by comparing the frequency before and after irradiation. Initial results in the treated birds were highly variable. Considerable reduction in the variability of response was obtained by control of dose, agglutinogen titer, breed, age and sex. Data was also obtained showing that there were individual differences in response to irradiation.

Significant increases in the frequency of the inagglutinable cells over that of the controls were obtained for both males and females at 2 and 4 months following irradiation with 360 r.

The relation of cell age to inagglutinability was tested by comparing the inagglutinable cell frequency of isolated young cells with that of the total cell population. The comparable frequencies which were observed indicate that cell age is not related to "A"-inagglutinability.
"A"-Antigen Variation in Pigeon Erythrocytes
Authors: HIERHOLZER J. C. , SCHEINBERG S. L. , HANSEN P. A.
Published: October 2019

Experiments were carried out for testing selection effects against the "A"-inagglutinable red cells. Three birds picked at random and not exposed to x-irradiation showed decreases in the number of inagglutinable cells in a Cr51-labeled cell population at 7 days. Two of these decreases were quite large, being >5-fold, and the three averaged an ICF change of -3.57-fold. The substantial reduction in survival of the "A"-inagglutinable cells was attested by the lowered inagglutinable cell frequency at 7 days postinfusion.

Seven birds uniform in titer and in their negative response to previous irradiation (360 r) averaged a 3.75-fold decrease in ICF at 8 days postinfusion. Four birds of a similar group but which had been very responsive to previous irradiation were treated in identical fashion. At 8 days postinfusion the average change in ICF was +0.80. This change is not significant, being within the experimental error of ±1.5-fold.

The marked difference in results between the "low-response" group (-3.75 ±0.56) and the "high-response" group (+0.80 ±0.88) was interpreted to be due to negative selection operating strongly in the former group.
Myeloma Proteins, Bence Jones Proteins and Normal Immunoglobulins in Multiple Myeloma
Authors: CAGGIANO VINCENT , CUTTNER JANET , SOLOMON ALAN
Published: October 2019

The relationship between the anomalous and normal immunoglobulins was studied through measurement of myeloma protein (MP), Bence Jones protein (BJP), and the normal γG, γA, γM and γD-globulin levels in a large group of patients with multiple myeloma. These determinations were made prior to and after initiation of three different therapeutic protocols.

Thirteen out of 18 patients had at least a 25 per cent reduction in MP or BJP within 6 months. This response was characterized by considerable variation both in the rate and period of time before the anomalous proteins decreased. The type of response was independent of (1) light chain type (K or L) of G or A-MP, (2) heavy chain subgroup or genetic (Gm) factors of G-MP, and (3) electrophorectic mobility of the MP. The ratio among multiple components of heterogenous G or A-MP was not altered by therapy. The initial level of MP, in the case of patients with G-MP, may be one factor in the type of response observed.

The rate of reduction of MP and BJP was extremely rapid in patients who received prednisone in conjunction with melphalan. It appeared that synthesis of anomalous γ-globulin components was completely suppressed with this treatment regimen. This type of response was not observed in patients treated with melphalan alone.

The mean values for each of the normal immunoglobulin (IG) classes (γG, γA, γM and γD-globulin) were reduced below normal. Two classes, γA and γD-globulin, were particularly low. Prior to therapy, however, the extent of reduction of each IG class varied in an individual patient. An inverse relationship was found for γM-globulin and G-MP levels. Part of the normal γG-globulin in patients with G-MP was determined by measurement of Vi (γ2c) levels. Different patterns of response to therapy were noted for each class of IG. More commonly, the response of a normal IG was independent of the response of the anomalous protein and furthermore, could not be related to a particular treatment schedule. In some instances, therapy contributed to further suppression of normal IG levels.
Ultrastructural Differences Between Thymic and Lymph Node Small Lymphocytes of Mice: Nucleolar Size and Cytoplasmic Volume
Authors: HEINIGER H. J. , RIEDWYL H. , GIGER H. , SORDAT B. , COTTIER H.
Published: October 2019

Ultrastructural differences between small lymphocytes of the thymic cortex and those located in the cortical zone of lymph nodes of mice were examined by electron microscopy and cytometric methods. The particle size analyzer TGZ 3 (Zeiss) was used to measure the size-frequency distribution of nucleolar cross-section diameters, and the resulting data were computed mathematically and statistically to determine the corresponding mean volumina.

It could be shown that thymic, as compared to lymph node cortical small lymphocytes, (1) have a smaller mean nucleolar volume (0.11µ3 versus 0.46µ3); (2) represent a more uniform population with regard to the frequency distribution of the nucleolar cross section diameters; and (3) are of smaller size due to less cytoplasm, while the mean nuclear volume does not differ significantly from that of small lymphocytes located in the cortex of lymph nodes.

These findings are discussed in relation to qualitative ultrastructural peculiarities and probable differences in the magnitude of RNA turnover as estimated by the use of tritiated cytidine. The possible significance of cytometrically defined populations of small lymphocytes with regard to sensitized and nonsensitized cells is considered.
Studies on Lymphocytes
Authors: SAFIER S. , WAGNER H. P. , COTTIER H. , JANSEN C. R. , RAI KANTI R. , CRONKITE E. P.
Published: October 2019

Two calves received 48 hours of extracorporeal irradiation of the circulating blood (ECIB) immediately prior to cannulation of the thoracic duct and administration of a single intravenous injection of 3H-thymidine. Lymph samples were then removed at short time intervals during 24 hours and smears from sedimented cells were processed for autoradiography. For different groups of mitotic figures classified according to size, cytoplasmic-nuclear ratio and degree of cytoplasmic basophilia, the variation of the mitotic labeling index (MLI) and of the mean grain count per labeled mitotic figure (MGC/LMF), as a function of time after a single injection of 3H-thymidine, was analyzed. Based on the pooled data obtained from the two animals, it was found that tinctorial properties of the cytoplasm permit differentiation into at least two populations of lymphoid cells in the thoracic duct of the calf: one of more basophilic cells with a mean DNA synthesis time of 4 hours and a mean generation time of 5½ to 6 hours and one or more populations of less basophilic cells with longer DNA synthesis and generation times.
In Vitro Studies of Insulin Inactivation with Reference to Erythroblastosis Fetalis
Authors: STEINKE J. , GRIES F. A. , DRISCOLL S. G. , Grinbush Maija
Published: October 2019

It was demonstrated that hemolysed blood and/or crystalline hemoglobin inactivated insulin either by irreversible destruction due to the presence of SH compounds or by reversible binding to hemoglobin. The increased pancreatic insulin content and pancreatic islet cell hyperplasia observed in infants with erythroblastosis fetalis may represent a compensatory response to inactivation of circulating insulin.
Protein Synthesis in Human Reticulocytes Induced by Therapy of Megaloblastic Anemia
Authors: BURKA EDWARD R. , MARKS PAUL A.
Published: October 2019

The capacity for protein synthesis has been investigated in peripheral blood reticulocytes which appear following initial replacement therapy in megaloblastic anemia. The rate of protein synthesis during the reticulocyte response correlated in general with the reticulocytosis. There appears to be no defect in the synthesis of protein in these cells. Evaluation of ribosome content and activity suggests that the cells appearing during the reticulocyte response are considerably heterogeneous with respect to degree of maturity. Changes observed during the course of the reticulocyte response are similar to those seen in maturing rabbit reticulocytes, suggesting that these cells mature subsequent to their appearance in the peripheral blood.
Hepatic Iron Deposition in Humans
Authors: FAWWAZ R. A. , WINCHELL H. S. , POLLYCOVE M. , SARGENT T.
Published: October 2019

In patients with spontaneous chronic low plasma latent iron-binding capacity, a large fraction of the intestinally absorbed iron is deposited in the liver without prior appearance in the systemic plasma. Such hepatic iron is not released to any large extent during the subsequent 2 weeks.

Our results are consistent with the hypothesis that iron absorbed from the intestinal tract is not initially bound to transferrin. When the plasma latent iron-binding capacity is normal, iron binds to transferrin prior to reaching the liver; when the plasma latent iron-binding capacity is low, a portion of the iron reaches the liver either unbound or abnormally bound to transferrin, resulting in its immediate hepatic deposition.
The Effect of Etiocholanolone on Granulocyte Kinetics
Authors: VOGEL JAMES M. , YANKEE RONALD A. , KIMBALL HARRY R. , WOLFF SHELDON M. , PERRY SEYMOUR
Published: October 2019

The effect of etiocholanolone on granulocyte kinetics in 12 hematologically normal patients has been investigated using the technic of 3H-DFP labeling of autologous blood in vitro.

Baseline determinations of the total blood granulocyte pool (TBGP), the circulating pool (CGP), and the marginated pool (MGP) were performed. The values for the total blood granulocyte pools were similar to those previously reported. Following the administration of etiocholanolone, there was a 98 per cent increase in the TBGP, which was considered to be due to mobilization of granulocytes from the bone marrow reserve. There was no change in the ratio of CGP to MGP.

These studies suggest that etiocholanolone may be a useful agent for the estimation of bone marrow reserve.
Congenital Pernicious Anemia with Coexistent Transitory Intestinal Malabsorption of Vitamin B12
Authors: LAMPKIN BEATRICE C. , MAUER ALVIN M.
Published: October 2019

Pernicious anemia with coexistent transitory intestinal malabsorption of vitamin B12 has been established in adults. In this report a child with congenital pernicious anemia was documented to have had transitory selective intestinal malabsorption of vitamin B12. The diagnosis of congenital pernicious anemia was established by the age of the patient, absence of intrinsic factor in gastric fluid, lack of antibodies to intrinsic factor and parietal cells, presence of HCl in gastric fluid, and normal gastric biopsy. The xylose excretion test, 72-hour fecal fat determination, upper gastrointestinal series, and biopsy of the jejunum were normal, but the Schilling test was abnormal with hog intrinsic factor of known potency on two occasions, indicating selective malabsorption of vitamin B12. Seven months after therapy the Schilling test was still abnormal without intrinsic factor, but was normal with both human and hog intrinsic factor. The normal absorption with intrinsic factor after therapy is indicative that the selective malabsorption which was originally present was probably a consequence of the vitamin B12 deficiency resulting from lack of intrinsic factor. In patients with abnormal radioactive vitamin B12 absorption tests with administration of intrinsic factor, coexistent pernicious anemia must be excluded by demonstration of intrinsic factor in gastric fluid.
ATP Metabolism in Pyruvate Kinase Deficient Erythrocytes
Authors: TWOMEY JEREMIAH J. , O’NEAL FLOYD B. , ALFREY CLARENCE P. , MOSER ROBERT H. , Hudson Wilma J.
Published: October 2019

Elevated levels of ATP were observed in pyruvate kinase deficient red cells from 5 patients despite increased ATP requirements because of increased ATPase activity. Increased red cell ATPase activity was associated with an excess of intracellular sodium. Residual aerobic glycolysis in reticulocytes did not contribute significantly toward ATP generation in these patients’ red cells. Their hemolytic anemia cannot be ascribed to a lack of high energy phosphate. Conversely, hemolysis in vitro appears to require a high energy phosphate dependent metabolic process.
Growth and Differentiation of Transplanted W/Wv Marrow
Authors: LEWIS JERRY P. , O’GRADY LOIS F. , BERNSTEIN SELDON E. , RUSSELL ELIZABETH S. , TROBAUGH FRANK E.
Published: October 2019

This paper reports new data on the effect of the action of the mutant genes W and Wv on murine hemopoiesis. Our studies demonstrate that the presence of these mutant genes produces: (1) a macrocytic anemia with neither granulocytopenia nor thrombocytopenia; (2) a severe defect in the early stages of hemopoietic repopulation manifested by (a) an apparent block in the differentiation of immature cells into erythroid precursors, and (b) a greatly reduced rate of proliferation of differentiated hemopoietic elements.

These data demonstrate the existence of genetic influence on repopulation and differentiation of transplanted marrow and suggest that severe anemia may result not only from defects in the late stages of erythroid development but also from abnormalities in the early stages of erythroid maturation and hemopoietic repopulation.
An Ultrastructural Basis for the Shape Changes Induced in Platelets by Chilling
Authors: WHITE JAMES G. , KRIVIT WILLIAM
Published: October 2019

Blood platelets normally circulate in the form of flat discs. Under conditions which promote aggregation, platelets transform from discs to irregular spheres and become sticky. Exposure of platelets to low temperature for brief periods causes similar shape changes. The present study demonstrates that the alterations induced in platelets by chilling are related to disappearance of a marginal bundle of microtubules, which has recently been described in platelets. Rewarming platelets which have previously been chilled results in recovery of both the marginal band of tubules and platelet disc shape. Thus the bundle of microtubules in platelet hyaloplasm appears intimately associated with disc shape of unaltered cells. Factors which influence platelet shape changes may do so by acting on the supporting marginal band of microtubules.
The Carbohydrate Metabolism and Respiration of Isolated Small Lymphocytes
Authors: PACHMAN LAUREN NT.
Published: October 2019

1. A homogeneous population of small lymphocytes with an average size of 6.7 micra was isolated from equine blood.

2. These cells could be maintained in vitro, with essentially complete survival for 24 hours, and with a 50% viability for five days.

3. The small lymphocytes consumed glucose at a rate of 1.87 mµmoles/1 x 107 cells/minute, and produced lactic acid at a rate of 2.30 mµmoles/1 x 107 cells/minute.

4. The oxygen consumption of small equine lymphocytes was 1.023 ± .165 mµmo1es oxygen 1 x 107 cells/minute, and that of mixed peripheral blood leukocytes, 1.25 ± .07 mµmoles oxygen/1 x 107 cells/minute, as determined, using a Clark oxygen electrode.

5. Lymphocyte glycolysis was stimulated under anaerobic conditions (Pasteur effect), and viability appeared unimpaired after 24 hours in a N2 environment.

6. Uncoupling of oxidative phosphorylation by the addition of 2,4, dinitrophenol stimulated both respiration and glycolysis.

7. The glycogen content of the normal small horse lymphocyte was 7.45 ± 1.04 µg glucose equivalents per 1 x 107 cells.

8. Many of the initial cell population were transformed into "blasts" following the addition of phytohemagglutin to the tissue culture medium. This response was associated with an increase in the rate of glycolysis and respiration by 24 hours, and a rise in intracellular glycogen by 48 hours.
The RNA Nucleotide Composition in Human Leukocytes from Normal and Leukemic Cases
Authors: KISS K. , ASTALDI G. , AIRÒ R.
Published: October 2019

The RNA-nucleotide composition of leukocytes from normal and leukemic patients has been analyzed. The amount of the four mononucleotides per 109 leukocytes is significantly increased in patients with either chronic lymphocytic or chronic granulocytic leukemia when compared with leukocytes from normal subjects. High values have been observed in acute granulocytic leukemia and during blastic crisis occurring in cases of chronic granulocytic leukemia. This suggests that the mononucleotide increase may be correlated with the number of blast cells. The molar base composition of the 4 mononucleotides and the ratio of 6-keto/6-amino acids and that of purine/pyrimidine bases in all leukemic cells examined were similar to the ratios occurring in normal leukocytes.

The significance of these findings, relative to the theory of viral origin of human leukemia, is discussed.
Study on Selective Single Cell Isolation Method for Blood Cells
Authors: NAGASAKI TADAKUNI
Published: October 2019

In this study a method of selective isolation of a human leukemic cell was described. The method consisted of (1) use of a micro-picking-up chamber with a very small micropipette (18µ in inner diameter), and coverslip pressor, and (2) use of a 70x phase objective lens with oil immersion condenser.

As an evidence of viability of the isolated cell, the nuclear rotation was demonstrated in a conditioned medium for five days culture.
Chromosomal Abnormalities in Multiple Myeloma
Authors: DAS K. C. , AIKAT B. K.
Published: October 2019

Chromosome studies were carried out in five cases of multiple myeloma by peripheral leukocyte culture and direct preparation from bonemarrow cells. No chromosomal abnormality was detected by leukocyte culture in any of these cases. Analysis of bone marrow metaphase plates revealed abnormalities in four out of five cases. Chromosomal changes were characterized by their variability from case to case, as well as among different groups of cells in individual cases. Both numerical and structural anomalies were encountered. The chromosome series more frequently involved were C, A, G and B in decreasing order. The diverse chromosomal aberrations encountered in these four cases of multiple myeloma are reminiscent of those described in acute leukemias.
Spindle Bridge and Mid-Body in Cultured Lymphocytes
Authors: SMITH G. F. , KOLB HELGA , FAUNCH JANET A.
Published: October 2019

Cultured human lymphocytes were prepared for electron-microscopic examination. From these cells observations were made on the structure of a spindle bridge and mid-body. It was estimated that the number of fibers in a spindle from cells containing 46 chromosomes is between 65 and 84.
Studies of Leukocyte Kinetics in Chronic Lymphocytic Leukemia
Authors: ZIMMERMAN THEODORE S. , GODWIN HERMAN A. , PERRY SEYMOUR
Published: October 2019

Intravenously administered H3TdR was used to study peripheral blood leukocyte kinetics of ten patients with CLL in relapse and one in partial remission. Two distinct patterns were found. The first pattern indicates the presence of a small, proliferating population of lymphocytes which is present in the blood for a relatively brief time. This pattern was found in patients with no organomegaly and with relatively lower peripheral lymphocyte counts. In the second pattern almost all of the cells present were non-proliferating and long-lived. The patients with the latter pattern had organomegaly. These studies support the concept that there is a progressive widespread accumulation of long-lived lymphocytes in CLL often leading to splenic pooling and, in some cases, hypersplenism.
Anti-Heparin Activity of Lysosomal Cationic Proteins from Polymorphonuclear Leukocytes
Authors: SABA HUSSAIN I. , ROBERTS HAROLD R. , HERION JOHN C.
Published: October 2019

The lysosomal cationic proteins (LCP) of rabbit polymorphonuclear leukocytes have previously been shown to inhibit the formation of intrinsic prothrombin activator. That they also have anti-heparin activity is now demonstrated in a thrombin-plasma clotting system, the partial thromboplastin time test and the thromboplastin generation test.

In thrombin clotting systems that contain antithrombin, LCP exhibit a clot-promoting effect. This activity does not appear to represent inhibition of antithrombin II or III or potentiation of the enzymatic action of thrombin. Rather it may be a direct effect on fibrinogen, or the reactions leading to fibrin formation.
The Effect of Etiocholanolone on The Entry of Granulocytes into The Peripheral Blood
Authors: GODWIN HERMAN A. , ZIMMERMAN THEODORE S. , KIMBALL HARRY R. , WOLFF SHELDON M. , PERRY SEYMOUR
Published: October 2019

The influence of etiocholanolone on normal granulocyte kinetics was studied in a group of hematologically normal individuals using H3TdR for cell labeling. Following the establishment of the baseline peripheral blood leukokinetic pattern in each individual, a second study was performed in which etiocholanolone was administered at varying times in relation to H3TdR. No influence upon the peripheral leukocyte kinetic patterns was detected when etiocholanolone was given prior to 74 hours. When given at that time, an accelerated release of labeled granulocytes from the bone marrow was produced. The degree of acceleration appeared to be related to the size of bone marrow granulocyte reserves.
Correlation of Granulocyte Mobilization with Etiocholanolone and the Subsequent Development of Myelosuppression in Patients with Acute Leukemia Receiving Therapy
Authors: GODWIN HERMAN A. , ZIMMERMAN THEODORE S. , KIMBALL HARRY R. , WOLFF SHELDON M. , PERRY SEYMOUR
Published: October 2019

1. Etiocholanolone was employed in the assessment of bone marrow granulocyte reserves in a group of patients with acute leukemia prior to the administration of therapy.

2. Normal levels of circulating white blood cells and granulocytes and/or remission bone marrow status were often associated with abnormal test responses.

3. Individuals having a positive test response experienced significantly less hematologic toxicity following therapy than did those patients having a negative response.

4. Etiocholanolone proved to be a safe agent without significant side effects.

5. This test can be helpful in the prediction of toxicity following antileukemic therapy.
Cell Migration from the Thymus to Other Lymphoid Organs in Hamsters of Different Ages
Authors: LINNA T. J.
Published: October 2019

Hamsters of different ages were labeled intra thymus and intravenously with 3H-thymidine. After extraction of nucleic acids, measurements of DNA content and tritium activity, the specific activity of different organs was calculated. By comparing the pattern of label of different organs after these quantitative measurements, it could be concluded that a good local labeling was obtained in all intra thymus injected animals, and a quantitatively significant transport of label could be shown to occur from the thymus to the mesenteric lymph nodes and Peyer’s patches in animals of both sexes, and also to the spleen of male animals. This transport was shown in 23 day old hamsters in which the lymphatic organs except the thymus still are immature. No such transport could be demonstrated in adult animals. Autoradiographic examinations also showed a good local labeling in the intra thymus injected animals and a migration of heavily labeled cells to mesenteric lymph nodes in 7 days old animals, and to mesenteric lymph nodes, Peyer’s patches and the white pulp of the spleen in 23 days old animals. Only single heavily labeled cells were found in the "peripheral" lymphatic organs of adult animals.
Erythrocyte Autoantibody Associated with Alpha-Methyldopa: Heterogeneity of Structure and Specificity
Authors: BAKEMEIER RICHARD F. , LEDDY JOHN P.
Published: October 2019

A case of Coombs-positive hemolytic anemia associated with alpha-methyldopa therapy was studied with particular attention to the structure and specificity of the erythrocyte autoantibodies. Eluted auotantibodies were found to be heterogeneous in both respects. Serologic evidence was obtained for the presence of at least four antibody specificities, all possibly related to the Rh complex: "anti-e," "anti-c," and at least two additional specificities for undefined antigens which may be a part of the hypothetic Rh "core" or precursor substance. The autoantibody population was found to contain γG globulins with both κ and λ light chains and three heavy-chain subclasses, in proportions approximating those found in normal human serum. These findings are judged to be most compatible with a response of basically normal lymphoid tissue to some antigenic alteration brought about by alpha-methyldopa or a derivative.