bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple Myeloma in Olmsted County, Minnesota, 1945-1964
Authors: KYLE ROBERT A. , NOBREGA FRED T. , KURLAND LEONARD T.
Published: October 2019

All cases of multiple myeloma diagnosed in bona fide residents of Olmsted County, Minnesota, during the years 1945 through 1964 were identified and reviewed. Pathologic material was available for reconfirmation of the diagnosis in 33 of the 35 cases reported. In the remaining two cases the diagnosis was based on roentgenologic findings and protein abnormalities as well as a typical clinical picture. The incidence rate for males was 1.9 times that for females. During the 20 year period covered in this study the average annual incidence rate in the total population has remained about 3/100,000 and when computed for persons 30 years of age and over, it is 6.3/100,000. Incidence figures by place of residence did not reveal a significant difference in the urban-rural rates. Myeloma was listed as a cause of death in 74 per cent of the death certificates. The mean survival time from onset in all cases was about 2 years, with a median survival of approximately 1 year. The age-specific rate increased with age, the highest rates being among male residents 80 years of age and older.
Studies of Human Erythrocyte Catalase by Fluorescent Antibody Technic The Distribution of Catalase in Acatalasia and Hypocatalasia
Authors: HOSOI TAKEMITSU , YAHARA SEIJI , HAMILTON HOWARD B. , FUJIKI NORIO , SASAKI TERUO , ISHIHARA YOSHINORI
Published: October 2019

In order to investigate the cellular distribution of catalase in normal, hypocatalasic and acatalasic red blood cells, the fluorescent antibody labelling technic was employed. Sensitive anticatalase sera were produced in rabbits by immunization with purified catalase extracted from human erythrocytes. Specificity against human erythrocyte catalase was confirmed by Ouchterlony’s double diffusion method.

The distribution of catalase is fairly homogeneous in normal and hypocatalasic red cells, but in acatalasic cells fluorescence due to the presence of catalase was not observed.

By this method the amount of catalase in hypocatalasic red cells was judged to be between that of normal and acatalasic red cells.
Development of a Myeloproliferative Disorder in Beagles Continuously Exposed to 90Sr
Authors: DUNGWORTH D. L. , GOLDMAN M. , SWITZER J. W. , McKELVIE D. H.
Published: October 2019

In a continuing study of the toxicity of 90Sr in beagles exposed continuously from mid-gestation to 1.5 years of age, a myeloproliferative disorder has arisen in dogs fed the two highest dose levels, 12 and 4 µCi 90Sr/day, respectively. Ten cases have occurred thus far at the highest level and 4 at the second highest, the difference in incidence being approximately equal to the threefold difference in dose rate. Age at onset has ranged from 14 to 72 months, and cumulative dose rates up to the time of death have varied from about 1,000 to 10,000 rads.

The 14 cases of myeloproliferative disorder present a morphologic spectrum which manifest in the acute form as granulocytic leukemia and in the chronic form resemble myelofibrosis with myeloid metaplasia (MMM). Anemia, poikilocytosis, anisocytosis, hypochromasia and terminal thrombocytopenia were constant features. Terminal leukocyte counts ranged from 3,300 to 38,900 cells/ mm3, with various degrees of shift to the left. Splenomegaly was the salient gross finding in most dogs. Major histologic lesions were pronounced granulocytic proliferation in bone marrow and spleen, with concomitant erythroid and megakaryocytic depletion. Liver, lymph nodes and a variety of other organs had less extensive and less frequent involvement. In the most acute cases, bone marrow and spleen contained cell populations composed almost entirely of blast cells.

This experimental situation should serve to shed light on fundamental aspects of radiation-induced granulocytic leukemia and might help to clarify the relationship between granulocytic leukemia and MMM.
Brief Report: Cytosine Arabinoside Therapy for Disseminated Herpes Zoster in a Patient with IgG Pyroglobulinemia
Authors: McKELVEY EUGENE M. , KWAAN HAU C.
Published: October 2019

Cytosine arabinoside is a new chemotherapeutic agent which inhibits DNA synthesis and has shown activity against experimental DNA virus infections. This drug was used to treat a 65 year old man with an IgG, Type K serum pyroglobulin accompanying a lymphoproliferative disorder who developed a fulminant, disseminated herpes zoster infection. Rapid attenuation of his disease was apparent. No new skin lesions developed after the second day of treatment and within 6 weeks the patient had achieved a complete recovery from his viral disease.
The Production of Schistocytes by Fibrin Strands (A Scanning Electron Microscope Study)
Authors: BULL BRIAN S. , KUHN IRVIN N.
Published: October 2019

The relationship between intravascular coagulation and schistocyte formation has been adequately documented in animal experiments and in in vitro models. A case report is presented of a patient who suffered from micro-angiopathic hemolytic anemia during life as a result of disseminated gastric adenocarcinoma. The fibrin microclots found in his vasculature on postmortem examination indicate that in intravascular coagulation, both in the human and in the experimental animal, fibrin initially polymerizes in the form of fine fibrin strands. These strands, the main etiologic factor in producing schistocytes, are constantly being lysed or rendered amorphous, and rarely persist in postmortem tissues except under unusually favorable conditions. Postmortem histologic study of one case where such favorable conditions did exist indicates the essential identity of the pathologic process in man and in experimental animals.
Effect of Phytohemagglutinin on Enzymes of Thymidine Salvage Pathway of Cultured Chronic Lymphatic Leukemic Lymphocytes
Authors: RABINOWITZ YALE , WONG POLLY , WILHITE BETTY A.
Published: October 2019

N-L and CLL-L prior to cell culture gave evidence of high activities of TdR phosphorylase, TMP and TDP kinases, while TdR kinase and phosphatase activities were relatively low. Cells cultured without PHA showed no appreciable alteration in enzyme activities during three to five days of culture. Response to PHA with blast-cell formation in cultures of N-L or CLL-L (low-count cases) was associated with increased TdR kinase activity which became prominent at the time of increased DNA polymerase activity and DNA synthesis during the second to third day of culture. Cells from cases of CLL-L with high WBC counts which failed to respond to PHA showed no increase in TdR kinase activity but did show increased phosphatase activity. Increased TdR activity and increased DNA polymerase activity may both be needed for increased synthesis of DNA to occur in lymphocytes responding to PHA.
Improvement of Leukocyte Bactericidal Activity in Chronic Granulomatous Disease
Authors: JOHNSTON RICHARD B. , BAEHNER ROBERT L.
Published: October 2019

Chronic granulomatous disease (CGD) is characterized by an inability of patients’ leukocytes to generate hydrogen peroxide and to kill non-peroxide-forming bacteria, such as staphylococci and serratiae. We have introduced glucose oxidase into CGD leukocytes in order to generate peroxide and thereby kill S. aureus and S. marcescens. These results support the concept that a leukocyte oxidative deficiency is primary to the pathogenesis of CGD.
Bullous Eruption and Elevated Leukocyte Alkaline Phosphatase in the Course of Busulfan-Treated Chronic Granulocytic Leukemia
Authors: DOSIK HARVEY , HUREWITZ DAVID J. , ROSNER FRED , SCHWARTZ JOEL M.
Published: October 2019

A 35-year-old man presented with a bullous eruption similar to erythema multiforme following the administration of high doses of busulfan therapy for chronic granulocytic leukemia. There was pancytopenia, hypoplasia of the bone marrow, elevation of serum vitamin B12 and B12 binding capacity and a paradoxical elevation of the leukocyte alkaline phosphatase level. Discontinuation of the busulfan and the administration of prednisone were followed by gradual healing of the skin lesions, reversal of the pancytopenia and reduction of the leukocyte alkaline phosphatase activity to zero. This case illustrates an unusual and previously unreported untoward response to busulfan and is another example of the capacity of the leukocytes in some patients with chronic granulocytic leukemia to develop high alkaline phosphatase activity in response to inflammation.
Melphalan Therapy of Polycythemia Vera
Authors: LOGUE GERALD L. , GUTTERMAN JORDAN U. , McGINN THOMAS G. , LASZLO JOHN , RUNDLES R. WAYNE
Published: October 2019

Twenty-seven patients with p. vera whose proliferative disease required the suppression of bone marrow function were treated with melphalan for periods of 20 to 72 months. The response was rated as good to excellent at three months in 24 of the 27 patients. At the end of one year 14 of the 27 patients had no evidence of disease. In eight of the remaining 13 the only persistent abnormality was a palpable spleen. Side reactions and adverse hematologic effects were infrequent. To date one patient has developed refractory anemia and evidence of myelofibrosis. Four patients have developed acute leukemia but none of these had been treated with melphalan alone. The results to date are sufficiently good to establish melphalan as one of the most effective agents in the control of p. vera.
Schwann Cells of the Bone Marrow
Authors: CALVO WENCESLAO , FORTEZA-VILA JERÓNIMO
Published: October 2019

Nerves containing numerous Schwann cells can be found in bone marrow with routine histological methods. Thin nerve bundles and single nerve fibers containing Schwann cells can be identified histologically with help of methods which demonstrate nerve fibers and myelin. Smears of marrow stained with the May-Grünwald-Giemsa method are not adequate for demonstration of nerve fibers, but their satellite Schwann cells appear well stained. Histological, cytological and ultrastructural characteristics of these cells are described in detail. Blood-forming cells and nerve fibers with their Schwann cells lie in close proximity throughout the marrow. This circumstance suggests that interaction may take place between both elements.
Comparison of Erythropoietin Response in Mice Following Polycythemia Induced by Transfusion or Hypoxia
Authors: OKUNEWICK J. P. , FULTON D.
Published: October 2019

Experiments were undertaken to measure the response to erythropoietin in mice during the first two weeks after the induction of polycythemia. A comparison of the size of the response obtained utilizing two different means of producing polycythemia was made. It was found that a 50 per cent higher level of iron incorporation was obtained if hypoxia was used rather than transfusion. It is suggested that this difference may be due to an alteration in both the compartment size and the cell cycle time of the erythropoietic stem cell in mice exposed to prolonged hypoxia.
Mechanism of Eosinophilia. III. Suppression of Eosinophilia by Agents Known to Modify Immune Responses
Authors: BOYER MARKLEY H. , BASTEN ANTONY , BEESON PAUL B.
Published: October 2019

Intravenous inoculation of Trichinella larvae into rats is followed by eosinophilia with a peak at 6 days. Reinjection of the parasites 20 days later results in an enhanced eosinophil response. This phenomenon may be analogous to the anamnestic antibody response which follows reinjection of antigenic material. Various agents known to modify conventional expressions of immunity were tested for their abilities to influence both primary and secondary eosinophil responses. Given in low single doses, methotrexate and cyclophosphamide could suppress the eosinophil response only after larval challenge; busulfan, prednisolone, bacterial endotoxin, Corynebacterium anaerobium and pertussis vaccine were effective only before the inoculum of parasites. The time-dependent action of these agents on eosinophilia is similar to their action on other systems of immune expression. Of further interest was the observation that certain of the agents which were suppressant when given before first larval challenge also appeared to affect "priming" for the second response. Eosinophilia appears to share common features with recognized immune phenomena. The model described may be useful in studying the cellular kinetics of immune responses, the action of immunosuppressive agents and other problems of cell differentiation or proliferation.
Hemolytic Anemia with Cold Detectable IgG Antibodies
Authors: MACKENZIE MALCOLM R. , CREEVY NANCY C.
Published: October 2019

Erythrocytes obtained from patients who manifest autoimmune hemolytic anemia can be divided into at least three categories by the nature of their protein coats as determined by direct antiglobulin (Coombs) test: IgG alone, IgG and complement (C), C alone. IgG antibodies were detected by direct Coombs Test at 4°C but not at 37°C in patients of type 3 A.H.A. Experiments at 4, 10, 15, 20, 30 and 37°C demonstrated that the IgG antibody was not eluted from the red cells at 37°C but apparently underwent a configurational change above 10°C such that agglutination no longer occurred with the Coombs reagent. This change was reversible. The presence of cold detectable IgG antibodies provides a mechanism for C deposition on erythrocytes in some cases of A.H.A., ostensibly due to complement alone.
Fetal Effects of Coumadin Administered During Pregnancy
Authors: HIRSH J. , CADE J. F. , GALLUS A. S.
Published: October 2019

The safest and most practical method of administering long-term anticoagulants in pregnancy is uncertain because treatment of the mother with vitamin K antagonists may be complicated by hemorrhage in the fetus. The effects on the fetus of giving coumadin in pregnancy was evaluated in rabbits. When coumadin was given from early pregnancy until term, all of the fetuses were stillborn with widespread hemorrhages. However, the fetuses were born alive and without hemorrhage when (1) coumadin was stopped 4-5 days before delivery, at which time the level of coagulation factors had almost returned to normal and (2) when delivery was performed by cesarean section at a time when the fetal coagulation defect was severe. It is suggested that the risk of fetal hemorrhage is high only when fetuses with a severe coagulation defect are exposed to the trauma of delivery.
Combination Chemotherapy With Nitrogen Mustard, Vincristine, Procarbazine and Prednisone in Previously Treated Patients With Hodgkin’s Disease
Authors: LOWENBRAUN STANLEY , DEVITA VINCENT T. , SERPICK ARTHUR A.
Published: October 2019

Combination chemotherapy with four drugs—nitrogen mustard, vincristine, procarbazine and prednisone—was used in 27 previously treated patients with advanced progressive Hodgkin’s disease. Six 2-week cycles of chemotherapy were administered in the following schedule: nitrogen mustard, 6 mg./sq.M. I.V., and vincristine, 1.4 mg./sq.M. I.V., on days 1 and 8 of each cycle; procarbazine, 100 mg./sq.M. by mouth daily throughout each cycle, and prednisone, 40 mg./sq.M. orally each day of cycles 1 and 4. Each cycle was followed by a 2-week period during which no drug was given. Twenty-two patients had Stage IV disease and 17 had systemic symptoms at the time of drug administration. All patients had histories of previous therapy. Two received chemotherapy alone, 15 had radiotherapy alone and 10 had both chemotherapy and radiotherapy. Nineteen out of the 27 patients (70%) had complete responses (total regression of all lesions) to the four drug combination and five patients (19%) had partial responses (50% regression of all lesions). Fourteen out of the 19 who responded completely are still in unmaintained remission 1-24 months from therapy completion. Eighteen out of the 19 who responded completely are still surviving from 6 to 30 months after the start of combination chemotherapy. Those patients treated previously with both radiotherapy and chemotherapy did not respond as well as patients treated with prior radiotherapy alone. In general, therapy was well tolerated, with leukopenia being the major dosage-limiting toxicity. There was a progressively poorer tolerance to the drugs with increasing extent of prior radiotherapy.
Erythrocyte Glyoxalase II Deficiency With Coincidental Hereditary Elliptocytosis
Authors: VALENTINE WILLIAM N. , PAGLIA DONALD E. , NEERHOUT ROBERT C. , KONRAD PATRICIA N.
Published: October 2019

Hereditary hydroxyacl-glutathione hydrolase (Glyoxalase II) deficiency was demonstrated in both homozygous and heterozygous form in kindred in which hereditary elliptocytosis was inherited independently. Homozygotes and heterozygotes for the enzyme deficiency were clearly differentiated by direct enzyme assay and a variety of indirect methods. Four homozygotes exhibited 10 per cent or less of normal activity. Leukocytes do not share the deficiency. Lactoyl-glutathione lyase (Glyoxalase I) activity was entirely normal in both leukocytes and erythrocytes, and was three times more active than Glyoxalase II. Glyoxalase II deficiency was traceable through three generations, was transmitted as an autosomal recessive trait and was not associated with discernible clinical or hematological abnormalities. It did not appear to worsen clinical manifestations of hereditary elliptocytosis where the two abnormalities coexisted.
Cellular Deformability: A Possible Determinant of the Normal Release of Maturing Erythrocytes From the Bone Marrow
Authors: LEBLOND PIERRE F. , LACELLE PAUL L. , WEED ROBERT I.
Published: October 2019

In vitro measurements of membrane and whole cell deformability indicate that erythroid maturation is accompanied by a progressive increase in cellular deformability. Early and intermediate normoblasts cannot be entirely deformed into a micropipette with dimensions like those of the apertures in the basement membrane which separates marrow hematopoietic cords from sinuses. Shape and nuclear rigidity are the most important determinants of rigidity in these immature cells. The marrow reticulocyte, with its distinctive clover-leaf configuration, still manifests significant intrinsic rigidity of its membrane and possibly underlying cytoplasm, which may be important to its normal retention in the bone marrow. However, further maturation is accompanied by a progressive decrease in membrane stiffness and, hence, resistance to traversing the micropipette. These results are interpreted to suggest that cellular deformability may be an important determinant of normal release of maturing erythrocytes from the bone marrow.
Analytical Review: Spontaneous Chromosomal Breakage and High Incidence of Leukemia in Inherited Disease
Authors: SCHROEDER TRAUTE M. , KURTH RENATE
Published: October 2019

Spontaneous chromosomal breakage has been found in six inherited diseases: ataxia telangiectasia, Bloom’s syndrome, Fanconi’s anemia, glutathione reductase deficiency, Kostmann’s agranulocytosis and pernicious anemia. These diseases are not equally well researched and the cytogenetic data are by no means uniform. However, in each disease, the incidence of leukemia is increased. Chromosomal breakage has been investigated primarily in vitro. In order to connect this phenomenon with each syndrome and with the development of malignancy, the relationship between in vitro results and in vivo events must be established. This relationship may be clarified through the use of direct chromosome preparations from the bone marrow and bone marrow smears. A few such investigations have been carried out. Any evaluation of the results must consider the complexity of the bone marrow in general, as well as in each disease and in each individual case. An understanding of in vivo events in turn would allow an evaluation of factors specific to the in vitro condition, and their ability to enhance, provoke or diminish breakage. It is our opinion that contradictory results from in vitro investigations are not yet confirmed. The kind of studies necessary for such confirmation is fairly clear and, until they have been carried out, it is premature to subgroup the various diseases. A complete understanding of these diseases is possible only when the primary metabolic defect is known. Pernicious anemia is well understood although the genetics remain to be clarified. Biochemical investigations of the other five diseases are still at a preliminary stage. However, a comparison of the cytogenetic data, the clinical picture, as well as the course of the diseases may lead to a conceptualization of the unknown metabolic defect. Although the primary causes for each disease differ they manifest themselves at the cellular level in vitro and/or in vivo as spontaneous chromosomal breakage. As a consequence of this phenomenon a change in the genetic material itself may create, by chance, primary yet unknown conditions for malignant growth. This may partially explain the correlation between spontaneous chromosomal breakage and leukemia. Methodical research in this field requires that blood cultures, bone marrow smears and direct chromosome preparations from bone marrow smears and direct chromosome preparations from bone marrow be included in the close following of the diseases. It is also imperative that the designation of types of chromosome aberrations be standardized and published in detail. This, together with continuing biochemical research will finally elucidate the primary defects involved.
Endogenous Production of 14CO: A Method for Calculation of RBC Life-span In Vivo
Authors: LANDAW STEPHEN A. , WINCHELL H. SAUL
Published: October 2019

In Endogenous Production of 14CO: A Method of Calculation of RBC Lifespan In Vivo, by Stephen A. Landaw and H. Saul Winchell (Blood 36: No. 5, November, 642-656), page 651, first paragraph, lines 10-15, the words "for example, in the normal rat … publication." should be omitted; second paragraph, line 6, "dicer" should read "differ;" Table 1, line 13, "T" should read "T."
Electrophoretic Patterns of Human Leukocyte Alkaline Phosphatase in Polycythemia Vera
Authors: BAXTER MARION F. , REINFRANK RALPH F.
Published: October 2019

Electrophoretic patterns of leukocyte alkaline phosphatase have been examined in seven normal and four erythrocytosis control subjects and in eight patients with polycythemia vera to determine whether changes occurred after chemotherapy. One major fast band and two narrow slow and intermediate bands of enzyme activity were found in both groups. There was no significant difference between the normal and erythrocytosis subjects. Mean values for the control group revealed that the slow band extended from the origin to 0.5 cm, the intermediate band from 0.5 to 1.0 cm, and the fast band from 1.5 to 5.0 cm, with the fast peak apex located 3.4 cm from the origin. In the eight polycythemia vera patients studied both before and after chemotherapy, there was a consistent and significant shift of the fast band from a location extending from 0.9 to 4.2 cm to a near normal position of 1.4 to 4.8 cm with a shift of the fast peak apex from 1.9 to 3.3 cm from the origin, after a remission was obtained. The slow and intermediate bands did not appear to be influenced by therapy.
Reactions of 14C-ADP and 14C-ATP With Washed Platelets From Rabbits
Authors: GUCCIONE M. A. , PACKHAM M. A. , KINLOUGH-RATHBONE R. L. , MUSTARD J. F.
Published: October 2019

Using suspensions of washed rabbit platelets that react to low concentrations of ADP in the same way as platelets in plasma, it has been found that the major change in added 14C-ADP is its conversion to 14C-ATP, catalyzed by nucleoside diphosphokinase at the platelet membrane. This enzyme is readily released from the platelets but the rate and extent of 14C-ADP to 14C-ATP conversion are greater in the presence of platelets than in the suspending fluid from which they have been removed. The platelets must provide the source of high-energy phosphate for the reaction, either from ATP released into the suspending fluid, or by the transfer of high-energy phosphate across the membrane. Thrombin stimulates the conversion, probably because it releases ATP from the platelets. Calcium and magnesium stimulate the conversion, whereas two of the inhibitors of ADP-induced aggregation (AMP and parachloromercuribenzenesulfonate) inhibit it. The ATPase activity of these platelets is low and it is not released into the suspending fluid. No adenylate kinase activity was demonstrable. The loss of high energy phosphate from the platelets that occurs during the conversion of 14C-ADP to 14C-ATP may be involved in the initiation of their response to ADP.
A Study of Aplastic Anemia in an Autopsy Series With Special Reference to Atomic Bomb Survivors in Hiroshima and Nagasaki
Authors: KIRSHBAUM JACK D. , MATSUO TAKESHI , SATO KAZUO , ICHIMARU MICHITO , TSUCHIMOTO TAISO , ISHIMARU TORANOSUKE
Published: October 2019

A study of the occurrence of aplastic anemia among atomic bomb survivors in Nagasaki and Hiroshima, Japan was made from a review of a series of 6327 autopsies from 1949 to June 1967 and the late effects of ionizing radiation were evaluated. There were 340 cases reviewed independently by a team of hematologists and pathologists. Of the 45 cases documented as aplastic anemia, 42 were definite and three were probable. Six additional cases were classified as probable. The cases were grouped into four categories depending upon the distance of the subject from the hypocenter at the time of the bomb (ATB). All patients fulfilled the requirement clinically of having pancytopenia. Bone marrow findings at autopsy from various sites revealed aplastic or hypocellular changes in 77.3%. The etiology in 42 cases was idiopathic, one case was drug-induced, one case received radiation for carcinoma of the cervix, and one case congenital in origin. No difference was noted in the exposed cases from the nonexposed. Of those who were exposed to 10 or more rad, the majority (four of five) died prior to 1955. On the basis of the data presented, there is no definite morphologic evidence that implicates ionizing radiation in the pathogenesis of aplastic anemia as a delayed complication of exposure in the A-bomb survivors.
Metabolism of Radio-iodinated Human Serum Albumin in Patients With Monoclonal Gammopathy
Authors: WELLS J. VIVIAN , FUDENBERG H. HUGH
Published: October 2019

(mean HSA level 3.3 g/100 ml, normal with 125I-labeled human serum albumin (HSA) in five patients with monoclonal gammopathy; three with Waldenström’s macroglobulinemia (one also had a γG monoclonal protein) and one patient each with γG multiple myeloma and γG benign gammopathy. Several abnormalities in HSA metabolism occurred in different combinations in different patients and no single consistent pattern was seen. The abnormalities included hypoalbuminemia (means HSA level 3.3 g/100, normal controls 4.7 g/100 ml); hypervolemia due to an expanded plasma volume (mean plasma volume 54.4 ml/kg, normal controls 41.0 ml/kg); decreased plasma and total body albumin pools; increased plasma localization of albumin; shortened plasma T ½; reduced fractional turnover rate; and reduced albumin synthesis rate. The most marked changes were noted in two patients with Waldenström’s macroglobulinemia who required plasma-pheresis for the hyperviscosity syndrome.
Appearance of Bone Marrow Smears With Necrotic Tumor Cells
Authors: BRITTIN GEOFFREY M. , BRECHER GEORGE
Published: October 2019

Bone marrow smears of necrotic tumor cells stained with Romanowsky dyes frequently have a definite reddish color that contrasts so strikingly with the blue color of normal marrow that necrosis may be suspected from gross examination. The bone marrow cells appear "smudged" and are difficult to identify on microscopic examination. Commonly, only a small amount of material is obtainable by ordinary needle aspiration of bone marrow containing necrotic tumor, and all of it is used to make smears. It is therefore important to recognize that bone marrow smears with a reddish gross appearance and in which the cells appear distorted and are difficult to identify may represent necrotic tumor and not an artifact produced by poor techniques.
Lymphocyte Production and Life-span in the Bone Marrow of the Guinea Pig
Authors: ROSSE CORNELIUS
Published: October 2019

Guinea pigs were given 14 daily injections of 3H-thymidine to label a proportion of cells with a slow rate of turnover in addition to rapidly proliferating cells. In the bone marrow the only unlabeled cells were some reticular, endothelial, and plasma cells, damaged cells, and 14.1% of small lymphocytes. Six weeks after discontinuation of 3H-thymidine 7% of the marrow lymphocytes remained labeled. In guinea pigs injected every 4 hr with 3H-thymidine for 4 days to label all cells entering DNA synthesis, 14.4% of small lymphocytes remained unlabeled along with some reticular, endothelial, phagocytic, monocytoid, damaged, and plasma cells. The pattern of appearance of labeled lymphocytes was consistent with the kinetics of transitional cells that function as their precursors. Thus, in the bone marrow of the guinea pig the majority of lymphocytes have a short lifespan and a rapid turnover, whereas about 14% turn over more slowly and 7% have a life-span exceeding 4 wk. In this respect the kinetics of marrow lymphocyte production differs from that of the rat.
Lymphocyte Membrane Enzymes. II. Cyclic 3',5'-Adenosine Monophosphatase Located on Unstimulated Human Small Lymphocyte Nuclear Membranes
Authors: COULSON ALAN S. , KENNEDY LESLEY A.
Published: October 2019

This study was undertaken to localize the enzyme cyclic 3',5'-adenosine monophosphatase in unstimulated human small lymphocytes. Cyclic AMP may be of importance in mediating lymphocyte stimulation, hence localization of the enzyme that is thought to modulate its intracellular concentration, cyclic AMPase, may point to the site of action of cyclic AMP in the cell. The histochemical technique employed was that of Shanta et al.6 Cyclic AMP substrate is degraded by the phosphodiesterase, then hydrolyzed, resulting in a lead phosphate precipitate at the site of enzyme action. This is subsequently visualized as lead sulfide. The enzyme was found to be localized on the nuclear membranes, which indicates that this is the site where cyclic AMP is destroyed. It does not necessarily mean that the nuclear membrane is the site where cyclic AMP is effective; this may be at some other point in the lymphocyte stimulation pathway, including the cell membrane, and the nuclear membrane may only be the site where cyclic AMP is degraded.
Mechanisms of Recovery From Neutropenia Induced by Hemodialysis
Authors: BRUBAKER LEONARD H. , NOLPH KARL D.
Published: October 2019

Profound, transient neutropenia is observed early in hemodialysis. The present studies were performed during 11 twin-coil dialyses in eight patients with chronic renal failure to determine if the rapid recovery reflects remobilization of sequestered neutrophils and/or if marrow reserves are utilized. In five studies, in vitro cell tagging with diisopropylfluorophosphate-32P (DF 32P) and reinfusion were performed 4-6 hr before routine hemodialysis. In all 11 studies a marked decrease of the absolute neutrophil count occurred within 15 min of starting blood return from the coil. In nine studies carried on over a sufficient period of time, a rebound of the neutrophil count to levels significantly higher than the highest control counts occurred by 1½-3½ hr after starting dialysis. In the radioactive studies during the rebound phase, most or all of the expected number of labeled neutrophils returned to the circulation, but simultaneously in all cases a large number of extra unlabeled neutrophils appeared in circulation. Since there are two sources for additional circulating neutrophils—the marginated pool and the marrow reserves—and since the marginated pool under the study conditions would be expected to have the same specific radioactivity as the circulating pool, the data are consistent with the hypothesis that there was an immediate marrow response to neutropenia.
Reversal of Resistance to Methotrexate in L1210 Murine Leukemia by Uracil
Authors: WALLERSTEIN HARRY , SLATER LEWIS M. , ENG BEN , CALMAN NEIL
Published: October 2019

BDF1 mice bearing L1210 leukemia, when treated with a regimen of uracil and methotrexate, show an increase in survival time greater than when treated with methotrexate alone. The uracil and methotrexate regimen also delays the development of methotrexate resistance as L1210 leukemia is transferred with therapy through multiple generations of mice. When uracil is applied to multiple generations of mice bearing tumor resistant to methotrexate, there is a return to sensitivity to methotrexate. It is also noted that uracil blocks the responsiveness of L1210 leukemia to 6-mercaptopurine.

The responsiveness of these tumor lines to the addition of uracil in their regimens was monitored by in vitro tritiated thymidine incorporation into DNA and by dihydrofolate reductase activities. These data, when integrated with survival time data, suggest that in part, the reported results are mediated by a uracil-induced reduction in the availability of dihydrofolate reductase and phosphoribosylpyrophosphate.
Inhibition of Fibrin Monomer Polymerization by Lambda Myeloma Globulins
Authors: Coleman Morton , Vigliano Edward M. , Weksler Marc E. , Nachman Ralph L.
Published: October 2019

Blood obtained from seven patients with lambda type myeloma proteins showed evidence of gelatinous bulky clots, impaired clot retraction, and circulating anticoagulant activity associated with interference of fibrin monomer polymerization. Five patients had γG1 and two had γA1 myeloma proteins. The pathologic plasmas and isolated myeloma proteins had anticoagulant activity that prolonged both thrombin and reptilase times, that was not absorbed by BaSO4 or neutralized by protamine sulfate, and that resisted heating to 56°C for 10 min. Addition of excess calcium partially corrected the anticoagulant effect. The anticoagulant activity of the isolated whole myeloma proteins, the enzymatic fragments, and polypeptide chains was measured by a thrombin time assay and a spectophotometric system with fibrin monomer. Low concentrations of the isolated IgGL proteins inhibited fibrin polymerization. The IgAL proteins did not demonstrate this activity at low concentrations but were active at concentrations comparable to in vivo levels. F(ab')2 and Fab fragments produced from the IgG proteins by enzymatic digestion possessed full inhibitory activity of the native intact proteins. Fc fragments and isolated polypeptide chains did not display significant anticoagulant activity. The results suggest that the Fab sites of certain lambda myeloma proteins may bind to fibrin during clotting and fibrin polymerization.
Migration of Cells From Shielded to Irradiated Marrow
Authors: Maloney Mary A. , Patt Harvey M.
Published: October 2019

Studies were made with CBA T6T6 chimeras to evaluate the contribution of migrating cells to the recovery of x-irradiated marrow. It was observed that cell migration from a shielded limb is essentially entirely responsible for the 30-day recovery of marrow irradiated with 1000 rad. Thus, these findings provide a direct demonstration of the generally accepted inference of stem cell migration from unirradiated to irradiated sites.
A HISTOCHEMICAL STUDY OF "ACID" AND "ALKALINE" PHOSPHATASE DISTRIBUTION IN NORMAL HUMAN BONE MARROW SMEARS
Authors: RABINOVITCH M. , ANDREUCCI D.
Published: October 2019

1. Three minute fixation in formol vapor at 44 C, followed by 15 minute washing proved to be the most satisfactory fixation procedure for both "acid" and "alkaline" phosphatase technics as applied to bone marrow smears.

2. For both technics a relation between staining intensity and cellular richness was found.

3. The reaction of normal human bone marrow cells to both phosphatase technics is described. Both are predominantly nuclear in location. Nuclear pattern approached that observed with common staining methods and Feulgen’s reaction. Cytoplasmic reaction was nearly negative. Nonspecific and specific granules do not stain after the "alkaline" technic. Nonspecific granules are negative for "acid" phosphatase, while specific neutrophilic are variable, and eosinophilic, constantly positive. Nucleoli are negative after the "acid" technic, being positive for the "alkaline" enzyme. Mitotic chromosomes are positive for both technics. "Acid" phosphatase reaction in cytoplasmic zones of lymphocytes, erythroblasts, plasmacytes and megakaryocytes, is described.
Impairment in Platelet Aggregation in Congenital Heart Disease
Authors: Maurer Harold M. , McCue Carolyn M. , Caul Joyce , Still W. J. S.
Published: October 2019

Platelet function and coagulation studies were performed on 65 children with congenital heart disease (CHD) and five wtih acquired heart disease, varying in age from 2 wk to 17 yr. Approximately 11% of the children with CHD had mild bleeding symptoms, and 9% had prolonged bleeding times, despite normal platelet counts. In 14 of 37 children (37.8%) with cyanotic CHD and four of 28 (14.3%) with the acyanotic variety, platelet aggregation by adenosine diphosphate (ADP), noradrenalin, and connective tissue suspension was impaired. The possibility of a platelet inhibitory factor in plasma was unlikely. Platelet content of ADP was normal, and high concentrations of exogenous ADP produced an improvement in aggregation, suggesting that the disturbance may be due to defective release of intrinsic ADP from the platelets. Impairment in aggregation was correlated with the severity of hypoxemia and polycythemia in cyanotic patients. Coagulation data did not support the concept that disseminated intravascular coagulation is a frequently associated finding in cyanotic CHD. Our findings reveal a disturbance in platelet function, until now, not commonly associated with CHD.
A Computer-based Teaching Program in Hemostasis
Authors: Gilchrest Barbara A. , Deykin Daniel , Bleich Howard L.
Published: October 2019

We have developed a natural language computer program that teaches a clinical approach to disorders of blood coagulation. The purpose of the program was fourfold: to teach a specific set of facts that we considered important to an understanding of hemostasis, to simulate an actual clinical setting in which the student determines the order and content of his patient evaluation; to be adaptive to a student’s responses; and to provide for ready retrieval of student responses. The program is now constructed in two sections. The first section comprises general purpose instructions to the computer that analyze and store input and display the next portion of the lesson according to rules that are independent of the text. The second element consists of specific teaching context. This format allows ready adaptation of the program to teaching other areas of hematology. Experience with the system demonstrates that new subject matter can be easily programmed and revised, that second-year medical students like the approach, and that the subject matter can be effectively taught.
An Analysis of Hematologic Disorders Presenting in the Private Practice of Hematology
Authors: Prager David
Published: October 2019

Many residents and fellows enter specialty training programs with vague notions as to what the clinical practice of their specialty will be like. Such speculation on the author’s part seems reasonable because the house staff is usually exposed to the specialty only in the hospital environment, and not in the private practitioner’s office. As well, there is little written information about the composition of a specialty practice. In order to evaluate the composition of a private hematology practice, 939 consecutive patients were evaluated as to their diagnostic categories. Such analysis reveals the following broad categories: anemias, 42%; white blood cell disorders, 12%; lymphomas and other nodes disorders, 12%; no hematological disorders, 12%; thrombocytopenia and allergic purpuras, 7%; plasma clotting disorders, 7%; splenic disorders, 4%; erythrocytosis, 2%; and plasma cell disorders, 2%. Each of the aforementioned categories were further subdivided into their specific diseases.
Kappa-Chain Deficiency
Authors: Bernier George M. , Gunderman J. Richard , Ruymann Frederick B.
Published: October 2019

A decreased concentration of immunoglobulin molecules of one light chain type (κ) was found in a young girl with recurrent respiratory infections and diarrhea. She had, in addition, decreased γA and γE globulin, partial albinism, and intestinal lactase deficiency. No eosinophils were detected in blood, bone marrow, or nasal smears. Radiolabeled κ- and λ -type molecules survived equally well, suggesting that the synthesis of molecules bearing κ-chains was decreased. The patient improved considerably with the regular administration of γ-globulin. It is possible that biological as well as chemical differences exist between immunoglobulins of the two light-chain types and that an optimal immune response is dependent on a normal complement of κ- and λ-chains.
Direct Assessment of Platelet Adhesion to Glass: A Study of the Forces of Interaction and the Effects of Plasma and Serum Factors, Platelet Function, and Modification of the Glass Surface
Authors: George James N.
Published: October 2019

Platelet adhesion to glass has been directly determined with a cover slip chamber. These studies have separated the functions of platelet adhesion to a foreign surface from platelet cohesion (aggregation). The forces of the platelet-glass interaction have been studied, and the qualitative variables affecting this interaction have been defined. Fibrinogen and calcium or magnesium are required for adhesion of either unwashed or washed platelets in plasma. Platelet adhesion in fresh serum requires thrombin and probably the fibrinogen of the platelet surface, since washed platelets are not adherent in fresh serum. Platelets incubated at 37°C for 48 hr can neither spread nor adhere to glass, a defect that may reflect decreased platelet surface area and membrane deformability. Platelets are equally as adherent to siliconized glass as to untreated glass surfaces. However, platelets cannot adhere to glass treated with the hydrogen-bonding polymer, poly(ethylene oxide). In contrast to silicone, poly(ethylene oxide)-treated glass surfaces do not impede blood coagulation. These surface properties further distinguish the two major factors involved in thrombogenesis: platelet adhesion and plasma coagulation.
Sideroblastic Anemia in Multiple Myeloma: A Preleukemic Change
Authors: Khaleeli M. , Keane W. M. , Lee G. R.
Published: October 2019

In a 10-yr observation period, 75 patients with multiple myeloma have been studied, and 55 of these were treated daily with low dose melphalan by mouth. Of these, four developed sideroblastic anemia, manifested by anemia, thrombocytopenia, aniso-poikilocytosis, and hypochromic stippled cells in the blood, and ringed sideroblasts in the bone marrow. In two patients, this complication occurred after more than 7 yr of therapy and at a time when there was no evidence of myeloma. In a third patient, it occurred when the myeloma relapsed, and in the fourth, myeloma was active but stable. The anemia did not respond to either folate or pyridoxine. In all four patients, acute myelomonoblastic leukemia developed within 6 mo after sideroblastic anemia had been detected. These observations suggest that sideroblastic anemia in myeloma is a preleukemic manifestation.
Relation Between Bleeding Time and Platelet Connective Tissue Reaction After Aspirin
Authors: Hirsh J. , Street D. , Cade J. F. , Amy H.
Published: October 2019

Aspirin prolongs the bleeding time in normal subjects and inhibits platelet release and aggregation with connective tissue and other biological agents. We have investigated one of the possible mechanisms by which aspirin prolongs the bleeding time by comparing the effects of aspirin and placebo on the bleeding time and platelet aggregation with connective tissue in normal volunteers. Two separate studies were performed. Both showed prolongation of the bleeding time and inhibition of the platelet connective tissue reaction after aspirin, but only the second study showed a significant correlation between these changes. Both studies are reported in detail because the discrepancy between them illustrates some important principles that require consideration when relating the effects of drugs on platelet function in vitro to their effects in vivo. The findings suggest that when particular care is taken to standardize the measurement of the platelet connective tissue reaction in terms of the stimulus used, subject variability, and analysis of results, the prolonged bleeding time after aspirin can be shown to be related to the defect produced in the platelet connective tissue reaction.
Studies on Regeneration of Heterotopic Splenic Autotransplants
Authors: Tavassoli Mehdi , Ratzan R. Judith , Crosby William H.
Published: October 2019

Fragments of spleen autotransplanted to subcutaneous tissue of the abdomen in the rat undergo almost complete necrosis and then regenerate into splenic tissue with a microscopic structure indistinguishable from the structure of the original organ. The regenerative process reminiscent of the spleen’s embryogenesis, originates from a shell of surviving splenic tissue at the surface of the implant. The regenerative zone first consists of almost monotonous connective tissue cells interspersed with red blood cells; it develops into splenic red pulp consisting of sinuses and intersinal cords. As capillaries develop, the structure of small arteries and peri-arterial lymphatic sheaths appear, and soon the structure of splenic white pulp becomes evident. Some 5 wk after autotransplantation, the splenic reconstruction is complete. The weight of the recovered tissue is a linear function of the weight of the implanted tissue; yet the linearity is lost when the weight of the implanted tissue exceeds 100 mg.
The Origin of Bone Marrow Fibroblasts
Authors: de la Chapelle Albert , Vuopio Pekka , Borgström Georg H.
Published: October 2019

Bone marrow aspirates from 12 patients with malignant hematologic disorders and abnormal bone marrow karyotypes were used to establish in vitro fibroblast cultures. The karyotypes of such fibroblasts were consistently normal. This finding is at variance with results presented by others. The origin of bone marrow-derived fibroblasts remains obscure.
Kinetic Parameters of Bone Marrow Stem Cells Using In Vivo Suicide by Tritiated Thymidine or by Hydroxyurea
Authors: Vassort F. , Winterholer M. , Frindel E. , Tubiana M.
Published: October 2019

The kinetics of colony-forming units (CFU) of the bone marrow in mice were studied using a method involving the suicide of cells in vivo by 3H-TdR or hydroxyurea. After selectively killing cells in S phase, the surviving cells traversed S phase in a cyclic fashion. This enabled the duration of the cycle and of the S phase of CFU to be measured—8 hr and 4 hr, respectively. It was shown that quiescent stem cells pass into the proliferative compartment. A computer model helped to explain the experimental results. The feedback mechanism seemed to be initiated by the depletion of the compartment of maturing cells. This hypothesis is supported by the fact that the CFU response to S-phase cell killing was similar in two strains of mice and was independent of the proportion of CFU in S phase, which was approximately 0% in the C57BI and 20% in the C3H mice.