Showing papers in "American Journal of Hematology in 1976"
TL;DR: The observations suggest the presence of significant migration of BFU‐E in mice under erythropoietic stimuli and stress the importance of studies on all hemopOietic organs in the assessment of murine hemopoiesis.
Abstract: Using a methylcellulose cell culture technique, we studied the serial changes in erythropoietic precursors in the femur, spleen, and blood of mice under erythropoietic stimuli. Phenylhdrazine hydrochloride, in the dosage of 60 mg/kg, was injected into mice subcutaneously on days 0, 1, and 3, and mice were sacrified on days 0, 2, 4, 7, and 10 for assessment of erythropoietic precursors. Significant changes were observed for all hemopoietic organs in the number of erythrocytic burst-forming units (BFU-E) and erythrocytic colony-forming units (CFU-E). Only BFU-E were present in blood, and their maximal increase was noted on day 2. While marrow BFU-E continuously decreased, maximal increase of CFU-E noted on day 4. Splenic BFU-E and CFU-E increased until day 4 and declined subsequently. These observations suggest the presence of significant migration of BFU-E in mice under erythropoietic stimuli and stress the importance of studies on all hemopoietic organs in the assessment of murine hemopoiesis.
139 citations
TL;DR: The objective of this investigation was to determine the physiological significance of these sialyl residues to the viability of erythrocytes in circulation.
Abstract: Sialic acid has been detected on the erythrocyte surface of a number of different species of animals. The objective of this investigation was to determine the physiological significance of these sialyl residues to the viability of erythrocytes in circulation. Methods have been described for the determination of total sialic acid on red blood cells and the conditions under which it may be released with sialidase. Chicken, dog, goat, and rabbit were chosen for these studies because of the differences in the amount (3 X 10(6) - 72 X 10(6) resides per erythrocyte), and type (N-acetyl-or N-glycolyl-neuraminic acids) of sialic acid found on the surface of their erythrocytes. Radioactive tagging with Na251CrO4 was used to monitor the effect of sialidase on the viability of erythrocytes upon autologous transfusion. By the two criteria used to assess the viability of erythrocytes-the percentage of erythrocytes surviving 24 hr after the autologous transfusion, and the half-life of those red blood cells in circulation that survive the first 24 h after the autologous transfusion, and the half-life of those red blood cells in circulation that survive the first 24 hr-it is apparent that the presence of sialic acid on the cell surface is crucial for the survival of nonnucleated mammalian erythrocytes. The loss of viability of dog erythrocytes can be elicited by the removal of approximately 10% of the total sialic acid. In marked contrast to the behavior of mammalian erythrocytes, sialidase-treated chicken erythrocytes appear to retain their viability in circulation.
105 citations
TL;DR: In the overwhelming majority of cases the findings suggested clonal identity of the leukemic cell population in relapse with that studied at the onset of the disease, notwithstanding considerable karyotypic instability in almost half of the patients.
Abstract: Sequential long-term cytogenetic studies in 71 children with acute leukemia were designed to investigate the nature of relapse after prolonged remission. In the overwhelming majority of the cases the findings suggested clonal identity of the leukemic cell population in relapse with that studied at the onset of the disease, notwithstanding considerable karyotypic instability in almost half of the patients. In a small minority an independent origin of the relapse clone could not be excluded on cytogenetic grounds but was considered unlikely, since mechanisms capable of accounting for the changes observed in these patients could be demonstrated in other cases. The persistence of diploid leukemic cells in the presence of an aneuploid subclone was demonstrated in the relapse bone marrow and/or spinal fluid in all active phases of the disease. On this basis the conversion from an aneuploid to a predominantly or exclusively diploid karyotype could be visualized, and a new model of clonal evolution, involving repetitive formation of abnormal karyotypes from a surviving diploid clone could be suggested.
95 citations
TL;DR: A periodic transfusion program was begun at the Children's Hospital of Michigan in 1969 and of 15 children currently on the program, none have had progression of neurologic abnormalities, and several have had definite improvement in neurologic function.
Abstract: CNS infarction is a devastating complication in sickle cell anemia. Episodes are frequently repetitive and often result in permanent neurologic abnormalities. In an attempt to prevent such recurrences a periodic transfusion program was begun at the Children's Hospital of Michigan in 1969. Twenty-one children currently on the program receive buffy-coat poor transfusions on an out-patient basis every 3 weeks. Of 15 who have been on the program for periods of from 9 months to 5 3/4 years, none have had progression of neurologic abnormalities, and several have had definite improvement in neurologic function. One child who was not brought in regularly had recurrent CNS infarction. The only recognized complication has been one instance of serum hepatitis. While such a transfusion program is not without risk, it seems an effective way of preventing progression of neurologic abnormalities resulting from recurrent CNS infarction in sickle cell anemia.
95 citations
TL;DR: Comparison of mortality rates from very diverse series of patients yielded quite consistent results and indicated superiority of effective chemotherapy over irradiation or inferior drug schedules.
Abstract: Median survival figures are essentially worthless for evaluation of the effectiveness of therapy in different series of patients with chronic myelocytic leukemia. Such data are heavily influenced by the characteristics of the initial patient mix, which play the major role in determining mortality during the first year of treatment. The effects of differing initial proportions of poor-risk patients are dissipated within two years, however, and the annual mortality rates thereafter reflect the influence of antileukemic therapy. Comparison of these rates, from very diverse series of patients, yielded quite consistent results and indicated superiority of effective chemotherapy over irradiation or inferior drug schedules.
84 citations
TL;DR: Cyclophosphamide therapy offers additional means of treating patients with ITP who fail to respond to conventional therapy and may serve as an alternative to splenectomy when surgery is contraindicated.
Abstract: Cyclophosphamide, an immunosuppressive agent, was administered as an additional mode of therapy to 30 patients with idiopathic thrombocytopenic purpura (ITP) refractory to conventional management. Of 22 previously tested by splenectomy an excellent response was achieved in 12, who remained in complete hematologic remission for 14-96 months after therapy was discontinued; a fair response in 3, with definite increase in platelets, but not to normal levels; and a poor response in 7 who failed to improve. Of 8 nonsplenectomized patients who failed to respond to steroids or maintain a response after steroids were discontinued, 4 were considered excellent, 1 required continued therapy to remain in remission (good response), 2 were fair, and 1 was poor. Remission was observed in 2-10 weeks in both groups and appeared to be related to duration of disease; presence of disease for less than 1 year was associated with a much better response to treatment (11 of 15) when compared with disorders lasting over 2 years (6 of 15). Cyclophosphamide therapy offers additional means of treating patients with ITP who fail to respond to conventional therapy and may serve as an alternative to splenectomy when surgery is contraindicated.
82 citations
TL;DR: All human T lymphoblast cell lines have been derived from subjects with leukemia secondary to thymic lymphoblastic lymphoma, a T cell malignacy, suggesting that such lines represent established cultures of neoplastic T cells.
Abstract: All human T lymphoblast cell lines have been derived from subjects with leukemia secondary to thymic lymphoblastic lymphoma, a T cell malignacy, suggesting that such lines represent established cultures of neoplastic T cells. Based on this observation, we prepared rabbit antisera to T cell line HSB-2, removed reactivity for histocompatibility antigens and normal T cells by absorption with autocthonous B cell line CCRF-SB and normal thymocytes, and tested the absorbed antisera by complement-dependent cytotoxicity against a panel of normal and malignant cells.
A representative antiserum reacted with all 4 T cell lines (mean cytotoxic index = 56) and with tumor cells from 4 patients with T cell lymphma (mean cytotoxic index = 50) but did not react with tumor cells from 6 patients with other types of leukemias (mean cytotoxic index = 2), with 3 B cell lines (mean cytotoxic index = 1), normal peripheral blood lymphocytes (mean cytotoxic index = 5), or normal thymocytes (mean cytotoxic index = 6). We conclude that appropriately absorbed antisera to human T cell lines detect T cell lymphoma tumor antigens.
67 citations
TL;DR: A family study spanning four generations revealed a total of 10 members with antithrombin III deficiency, two teenage brothers with recurrent thromboembolic disease and five of the 10 affected family members have had thrombotic problems.
Abstract: Two teenage brothers with recurrent thromboembolic disease were found to have antithrombin III deficiency. A family study spanning four generations revealed a total of 10 members with antithrombin III deficiency. Five of the 10 affected family members have had thrombotic problems. Antithrombin III deficiency was documented by coagulation assays measuring heparin cofactor, anti-Factor Xa, and progressive antithrombin activity; the level of antithrombin III antigenic material measured by immunoelectrophoresis was low in subjects with abnormal coagulation assays. The clinical features which may lead one to suspect the hereditary hypercoagulable condition of antithrombin III deficiency are reviewed.
66 citations
TL;DR: Three distinctive groups of patients were identified on the basis of the analysis of blast cells for surface immunoglobulin, sheep erythrocyte rosette formation, and complement receptors, and Elevated white blood cell count indicate poor prognosis.
Abstract: Blast cell surface markers for T- and B-lymphocyte characteristics were studied at diagnosis in 73 children with non-Hodgkin's lymphoproliferative malignancies. Three distinctive groups of patients were identified on the basis of the analysis of blast cells for surface immunoglobulin (SIg), sheep erythrocyte (sE) rosette formation, and complement receptors, The seven group I patients had monoclonal IgM on their blast cells, morphologic features of Burkitt's lymphoma, abdominal masses, and very short survival. The 13 group II patients had receptors for sE, complement, or both on their blast cells, mediastinal or nodal masses, and short survival. The distinction between leukemia and lymphoma based on the presence of bone marrow involvement at diagnosis is not prognostically useful in this group of patients. The blast cells of group II patients could not be morphologically distinguished from those of the group III patients. The 53 groups III patients had SIG, sE, and complement negative blast cells and could be further subdivided on the basis of while blood cell count. The nine group IIIA patients (greater than 100.0 X 10(9)/liter) had in general short survival, while most of the 44 group IIIB patients (less than than 100.0 X 10(9)/liter) have remained in complete remission. Positive surface markers, mass lesions, male sex, and age of diagnosis less than 2 years of greater than or equal to 10 years appear to be interrelated factors indicating poor prognosis. Elevated while blood cell count is a prognostic indicator independent of surface marker analysis or presence of mass lesions.
52 citations
TL;DR: These studies provide evidence that the committed granulocyte‐monocyte stem cell has a glucocorticoid receptor mechanism that when activated results in inhibition of cellular proliferation in vitro.
Abstract: The effect of dexamethasone on mouse bone marrow granulocyte-monocyte precursor cells (CFU-C) was studied in vitro. Dexamethasone inhibited colony formation in the presence of maximally stimulating concentrations of colony-stimulating activity. A mean colony reduction of 55% occurred at 10(-9) M dexamethasone and inhibition was observed at concentrations as low as 10(-12)M. The dexamethasone suppression could be abrogated by progesterone. These studies provide evidence that the committed granulocyte-monocyte stem cell has a glucocorticoid receptor mechanism that when activated results in inhibition of cellular proliferation in vitro.
45 citations
TL;DR: It is concluded that laparotomy and splenectomy in children is essential for accurate staging but carries significant risk, and continuous penicillin prophylaxis is recommended.
Abstract: Twenty-five cases of Hodgkin's Disease (15 males and 10 females) aged 5 to 17 years were studied from April 1970 to July 1976 (75 month period). Histology revealed that 2 had lymphocytic predominance, 12 had nodular sclerosis, and 11 had mixed cellularity. Pathologic staging revealed that 3 were IA, 1 IB, 5 IIA, 4 IIB, 6 IIIA, and 6 IIIB. Laparotomy altered the staging in 12 patients (9 were staged up and 3 down). All but 2 patients received extended field radiation, and 5 had recurrence of disease and were treated with combination chemotherapy. Twenty-three are alive without evidence of disease (21–75 months), and the 2 deaths were not due to Hodgkin's Disease but to hemobilia (postliver biopsy) and penumococcal septicemia, purpura fulminans, and disseminated intravascular coagulation (14 months postsplenectomy). Other complications included 2 patients with intestinal obstruction, 1 with postoperative subphrenic abscess, and 1 with streptococcal septicemia and polyarthritis. Nineteen patients received continuous penicillin prophylaxis postoperatively and the 2 with serious infections were amongst the 6 who had not received penicillin or whose penicillin had been discontinued at the time of infection. It is concluded that laparotomy and splenectomy in children is essential for accurate staging but carries significant risk, and continuous penicillin prophylaxis is recommended.
TL;DR: It is concluded that current methods of detecting isosensitization to platelet alloantigens are less satisfactory than HLA phenotyping in selecting unrelated platelet donors for an alloimmunized patient population.
Abstract: Compatibility tests in which donor platelets were tested with recipient sera were performed retroactively after 64 transfusions of platelets from 59 unrelated donors to 10 alloimmunized patients. Techniques used were serotonin release, aggregometry, platelet factor 3 release, and lymphocytotoxicity, each of which has been advocated as a means of testing donor-recipient platelet compatibility. Although "false positive" reactions were few (positive crossmatch but satisfactory transfusion response), "false negative" reactions (negative crossmatch but poor transfusion response) were unacceptably high (43% by lymphocytotoxicity, 60% by serotonin release, 76% by platelet factor 3 release, and 83% by aggregometry). We conclude that current methods of detecting isosensitization to platelet alloantigens are less satisfactory than HLA phenotyping in selecting unrelated platelet donors for an alloimmunized patient population.
TL;DR: Observations are not consistent with the hypothesis of a progressive decrease in the supply of oxygen to the fetus during the later stages of gestation, to which the fetus adapts by increasing its hemoglobin concentration.
Abstract: The hemoglobin concentration, red cell count, hematocrit, reticulocyte count, and red cell size distribution were determined on skin prick blood obtained on the first postnatal day from infants born at various stages of gestation, from week 24 to term. During this period the hemoglobin concentration and hematocrit remained constant, around 19 gm/100 ml and 60%, respectively. The mean corpuscular volume decreased progressively, with a corresponding rise in the red cell count. The reticulocyte count decreased progressively from 9.6% to 3.7% during the period of observation. The red cell size distribution (Price Jones) curve was markedly shifted to the macrocytic side at 24-25 weeks. Thereafter, cells larger than 102 mu3 decreased gradually, while the percentage of smaller cells increased. These observations are not consistent with the hypothesis of a progressive decrease in the supply of oxygen to the fetus during the later stages of gestation, to which the fetus adapts by increasing its hemoglobin concentration.
TL;DR: A radioimmunoassay procedure was established that permitted identification and quantitation of each of these two minor hemoglobins in hemolysates containing other hemoglobin components and has a greater sensitivity than other commonly employed techniques.
Abstract: Hyperimmune antisera to chromatographically purified hemoglobins F and A2 were produced in rabbits and made specific for the immunogen by adsorption with normal human hemoglobin A conjugated to cyanogen bromide-activated agarose. A radioimmunoassay was established that permitted identification and quantitation of each of these two minor hemoglobins in hemolysates containing other hemoglobin components. The quantities of hemoglobins A2 and/or F present in hemolysates of individuals with beta-thalassemia, sickle cell anemia, Hb-C disease, and other hematological disorders were determined immunochemically, and the results were commpared to values obtained by microcolumn chromatography for the measurement of Hb-A2 or with the alkali denaturation technique in quantitating Hb-F. The immunoassay procedure has a greater sensitivity than other commonly employed techniques and can detect as little as 0.05 mug of these hemoglobins.
TL;DR: Most laboratories using cells cultured in vitro maintain multiple cell lines that should be monitored for species and intraspecies characteristics to prevent invalidation of research work due to incidents of cell line cross‐contamination.
Abstract: Most laboratories using cells cultured in vitro maintain multiple cell lines. Such lines should be monitored for species and intraspecies characteristics to prevent invalidation of research work due to incidents of cell line cross-contamination.
This report describes the results obtained when 246 cell cultures were examined for evidence of cross-contamination or mislabeling. Using species-specific antigens, isoenzyme electrophoresis, and chromosomes as markers of identity, 14% of the cultures submitted were found to be contaminated by cells of another species. Of human cell lines submitted 25% were of HeLa cell origin, as determined by 2 intraspecies markers, glucose-6-phosphate dehydrogenase and chromosome analyses. The fact that, overall, nearly 30% of the cell lines examined were incorrectly designated makes the importance of cell line monitoring self-evident.
TL;DR: The ratio of β to non‐β, or β to βS‐chains in sickle cell anemia approximated unity, whereas patients with HbS‐βO‐thalassemia had a deficit of β‐chain production relative to that of the β‐ chain.
Abstract: The diseases commonly confused with sickle cell anemia include sickle cell beta-thalassemia in which synthesis of betaA-chains are completely suppressed (HbS-betao-thalassemia). We obtained hematologic measurements and studied globin biosynthesis in five patients with this disorder and compared the results with those obtained in five patients with "mild" sickle cell anemia and seven individuals with sickle cell-beta-thalassemia having hemoglobin A levels of 20-30% (HbS-beta+-thalassemia). A distinction between HbS-betao-thalassemia and sickle cell anemia was not always possible on clinical, hematologic, or electrophoretic grounds. Thalassemia heterozygotes had hypochromia and microcytosis, not generally a feature of sickle cell anemia, although overlap of values did exist. The ratio of alpha to non-alpha, or alpha to betaS-chains in sickle cell anemia approximated unity, whereas patients with HbS-betao-thalassemia had a deficit of beta-chain production relative to that of the alpha-chain. The differentiation of HbS-betao-thalassemia and sickle cell anemia can be best made on the basis of family or biosynthetic study. We estimated the regional prevalence of HbS-betao-thalassemia to be 1:23,000 of the black population.
TL;DR: Between 1969‐1973, 75 consecutive children under the age of 15 years with acute lymphoblastic leukemia were treated with a multiple‐drug regimen (L‐2), and forty‐nine patients continue in complete remission from 23 to 63 months.
Abstract: Between 1969-1973, 75 consecutive children under the age of 15 years with acute lymphoblastic leukemia were treated with a multiple-drug regimen (L-2) Prophylaxis for meningeal leukemia was limited to the repeated intrathecal injections of methotrexate Seventy-four patients achieved remission; the duration of remissions could be evaluated only for 70 Relapse terminated complete remission within 1-54 months in 21 children Four of these relapses were confined to the central nervous system Forty-nine patients continue in complete remission from 23 to 63 months Chemotherapy has been discontinued in 29 children, and 25 of these remain without evidence of recurrence for 2-27 months posttreatment
TL;DR: The three‐dimensional world of the spleen was explored by scanning electron microscopy on both arterially perfused and nonperfused specimens, as well as on plastic corrosion casts of splenic vasculatures, establishing an anatomical basis for an often disputed “closed” circulation pathway.
Abstract: The three-dimensional world of the spleen was explored by scanning electron microscopy on both arterially perfused and nonperfused specimens, as well as on plastic corrosion casts of splenic vasculatures. Of 25 spleens studied, 18 were examples of hypersplenism. These were contrasted to 7 essentially normal spleens taken from children being staged for treatment of Hodgkin's disease whose spleens proved to be uninvolved in the pathologic process. Splenic sinuses in all 25 spleens were typified by a degree of porosity. RBC were caught in the act of entering sinuses from splenic cords. These sinus windows thus represent one end of an “open” circulatiion pathway. In casts of microvasculature, direct arteriovenous connections were demonstrated, thus establishing an anatomical basis for an often disputed “closed” circulation pathway.
Spleens from 7 patients with hereditary spherocytosis had a super abundance of red pulp. Splenic cords were thickened and crowded with spherocytes, many of which presented slightly wrinkled membranes, as were also noted on the peripheral blood RBC. It is possible that these membrane features are unique for HS and reflect the intrinsic membrane abnormality in protein composition. The 7 spleens from chronic idiopathic thrombocytopenic purpura had white pulp as the predominant region. Germinal centers were frequent. Lymphocytes and plasma cells with well-developed microvilli were suggestive that relese of antiplatelet antibody might be occurring in white pulp. Platelets were especially notable in peripheral white pulp and marginal zones. Platelet clumps were observed, generally adjacent to splenic macrophages.
TL;DR: Analysis of the pathways of arachidonic acid metabolism may furnish new insight into platelet function and into disorders of primary hemostasis.
Abstract: Washed human platelets take up arachidonic acid from plasma and incorporate the fatty acid into the major classes of complex lipids. Thrombin impairs net incorporation. It activates endogenous phospholipases which liberate arachidonic acid from phospholipids. As a consequence of thrombin induced aggregation platelets release arachidonic acid intermediates formed by the action of platelet fatty acid cyclooxygenase and by platelet fatty acid lipoxygenase. Cyclooxygenase, but not lipoxygenase, is inhibited by aspirin and indomethicin. Analysis of the pathways of arachidonic acid metabolism may furnish new insight into platelet function and into disorders of primary hemostasis.
TL;DR: The large increases of type I porphyrin with normal or increased formation of type III, both in the disease and in the hemolysates, are believed due to a primary increase of ALA‐S or UPG‐S activity rather than a decrease of Co‐S.
Abstract: Normal or increased amounts of series III porphyrins with greater amounts of series I were observed on incubation of PBG in hemolysates of congenital erythropoietic porphyria vs. normal erythrocytes, human or bovine. Correlation with reticulocyte percentage was poor, in the aggregate a general trend toward increased values of both isomers I and III was noted with increasing reticulocytes. When the percent of type III was low the net amount was increased as compared with normal. Hemolysates of non-porphyric, reticulocyte-rich red cells (hemolytic or posthemorrhagic anemia) formed only minute amounts of type I porphyrin but at the same time no more, or even less type III than the porphyric hemolysates, although representing red cells of greater reticulocyte content. No evidence of deficient heme synthesis was observed in porphyric hemolysates incubated with [14 C] -porphobilinogen or 59Fe. Other studies of porphyric hemolysates incubated with and without added mouse spleen synthetase failed to reveal evidence of an absolute UPG-III cosynthetase (Co-S) deficiency. The large increases of type I porphyrin with normal or increased formation of type III, both in the disease and in the hemolysates, are believed due to a primary increase of ALA-S or UPG-S activity rather than a decrease of Co-S. Possible mutations which might be responsible for this increase are considered.
TL;DR: Findings are consistent with the hypothesis that cyclic neutropenia is caused by a quantitatively decreased entry of stem cells or granulocytic progenitor cells into granulopoiesis.
Abstract: Cellular and humoral factors involved in the regulation of granulopoiesis were evaluated in two patients with cyclic neutropenia by utilizing the agar-gel marrow culture technique to serially study marrow granulocytic colony-forming capacity (CFC) and the urinary output of colony-stimulating factor (CSF). CSF output varied inversely with peripheral neutrophil counts and directly with monocyte counts and evidence for infection (endotoxemia and/or staphylococcal abscesses). Following autologous infusion of one patient's plasma obtained during a period of neutropenia, increased urinary excretion of CSF occurred concomitant with increments in both marrow CFC and the proportion of granulocytic progenitor cells in DNA synthesis. Neutrophil periodicity was not altered by the administration of the neutropenic plasma. These findings are consistent with the hypothesis that cyclic neutropenia is caused by a quantitatively decreased entry of stem cells or granulocytic progenitor cells into granulopoiesis.
TL;DR: Diagnostic and screening methods for beta‐thalassemia trait are reviewed in the order of their development, including identification by homozygous offspring, erythrocyte morphology, osmotic fragility, hemoglobin composition, globin synthetic rates, and red blood cell indices.
Abstract: Diagnostic and screening methods for beta-thalassemia trait are reviewed in the order of their development, including identification by homozygous offspring, erythrocyte morphology, osmotic fragility, hemoglobin composition, globin synthetic rates, and red blood cell indices.
TL;DR: A protocol for the prophylaxis of CNS leukemia was devised involving intermittent low‐dosage radiation of the craniospinal axis combined with single intrathecal injections of MTX which suggests that leukemic colonization of the CNS is not restricted to the initial stage of the disease and that periodic measures might be advantageous.
Abstract: A protocol for the prophylaxis of CNS leukemia was devised involving intermittent low-dosage radiation of the craniospinal axis combined with single intrathecal injections of MTX. The retionale for this protocol was the timing of first CNS relapses in patients not receiving prophylaxis which suggests that leukemic colonization of the CNS is not restricted to the initial stage of the disease and that periodic measures might be advantageous. The low dosage of radiation was chosen because it is well tolerated and has been found temporarily effective in overt CNS relapse. The two series of patients were comparable as to various parameters. Results after three years of observation were comparable to those obtained by others with a single initial course of high-dose radiation, with an expected 50% uninterrupted complete 5-year remission. On the basis of 30 months follow up in 26 patients, the therapy is well tolerated. An increase in morbidity due to infections in remission was not associated with a higher mortality.
TL;DR: Not only do arteriovenous connections exist in human spleens, but their frequency, as revealed by methods accentuating three‐dimensional aspects of the splenic microcirculation, justify future reconsiderations of the functional significance of this closed type of circulation.
Abstract: The mission of this study was to determine whether or not arteriovenous connections, indicative of a “closed” type of circulation, existed in the human spleen. Spleens from four patients requiring therapeutic splenectomy were the basis for this report. Scanning electron microscopy of plastic corrosion casts, prepared from these four spleens, revealed direct vascular conduits between splenic pulp arteries or arterial capillaries and the venous sinuses in the red pulp. Also demonstrated were a few arteriovenous shunts between pulp arteries or arterial capillaries and pulp or trabecular veins. Inclusion of sized microspheres in low-viscosity perfusion plastic illustrated that some diameters of the connecting shunts were 7-10 μm, with other shunts even smaller. Not only do arteriovenous connections exist in human spleens, but their frequency, as revealed by methods accentuating three-dimensional aspects of the splenic microcirculation, justify future reconsiderations of the functional significance of this closed type of circulation.
Examination of samples of the same intact spleens, prepared by freeze-fracture and conventional critical-point drying, also revealed an “open” type circulation structure, namely, pore-patterned sinus walls that could facilitate blood cell movement from pulp cords into venous sinuses. Scanning electron microscopy thus has provided direct evidence that human spleens have both “open” and “closed” circulatory pathways in their microvasculature.
TL;DR: FMF cells demonstrated a slight decrease in their ability to migrate randomly in capillary tubes, this was primarily seen in Armenian patients and in those experiencing an acute attack.
Abstract: Neutrophilic leukocytes of patients with familial Mediterranean fever and of normal control subjects were studied in vitro. FMF neutrophils were found to be morphologically normal by light and electron microscopy and to have normal quantities of the lysosomal enzyme lysozyme. FMF cells demonstrated a slight decrease in their ability to migrate randomly in capillary tubes, this was primarily seen in Armenian patients and in those experiencing an acute attack. The leukocytes of these patients functioned normally in regard to their chemotactic and Candida-killing activity.
TL;DR: Two new variants of glucose 6‐phosphate dehydrogenase (G6PD) deficiency associated with chronic nonspherocytic hemolytic anemia were discovered in Japan and are clearly different from hitherto described G6PD variants, including the Japanese variants Gd (‐) Heian and Gd(‐) Kyoto.
Abstract: Two new variants of glucose 6-phosphate dehydrogenase (G6PD) deficiency associated with chronic nonspherocytic hemolytic anemia were discovered in Japan. Gd(-) Tokushima was found in a 17-years-old male whose erythrocytes contained 4.4% of normal enzyme activity. Partially purified enzyme revealed a main band of normal electrophoretic mobility with additional two minor bands of different mobility; normal Km G6P, and Km NADP five-to sixfold higher than normal; normal utilization of 2-deoxy-G6P, galactose-6P, and deamino-NADP; marked thermal instability; a normal pH curve; and normal Ki NADPH. The hemolytic anemia was moderate to severe. Gd(-) Tokyo was characterized from a 15-year-old male who had chronic nonspherocytic hemolytic anemia of mild degree. The erythrocytes contained 3% of normal enzyme activity, and partially purified enzyme revealed slow electrophoretic mobility (90% of normal for both a tris-hydrochloride buffer system and a tris-EDTA-borate buffer system, and 70% of normal for a phosphate buffer system); normal Km G6P and Km NADP; normal utilization of 2-deoxy-G6P, galactose-6P, and deamino-NADP; greatly increased thermal instability; a normal pH curve; and normal Ki NADPH. These two variants are clearly different from hitherto described G6PD variants, including the Japanese variants Gd(-) Heian and Gd(-) Kyoto. The mothers of both Gd(-) Tokushima and Gd(-) Tokoyo were found to be heterozygote by an ascorbate-cyanide test.
TL;DR: Based on total numbers at remission the reduction in B cells was greater than in T cells, and the most marked changes occurred during sanctuary therapy, where a reduction in the mean serum immunoglobulin was associated with decreasing B cell numbers.
Abstract: In order to evaluate the effect of radio- and chemotherapy on immunity, T and B lymphocyte surface receptors were studied sequentially in the blood from 28 previously untreated leukemic children. Following the initiation of chemotherapy an increase in the percent T and B cells was noted in the peripheral blood. In association with sanctuary therapy and chemotherapy there was a decrease in the total number of circulating T and B cells and a relative increase in lymphocytes lacking markers. Based on total numbers at remission the reduction in B cells was greater than in T cells, and the most marked changes occurred during sanctuary therapy. A reduction in the mean serum immunoglobulin was associated with decreasing B cell numbers.
TL;DR: It is suggested that an elevated factor VIII activity/factor VIII‐related antigen ratio may be used for detection of the carriers of von Willebrand's disease.
Abstract: Using monospecific rabbit antihuman factor VIII antiserum, we have examined the amounts of factor VIII-related antigen and compared these to the levels of factor VIII procoagulant activity in normal subjects and patients with von Willebrand's disease. We have observed that even without transfusion all nine probands with von Willebrand's disease and 20 of their 34 relatives possessed a significantly elevated factor VIII activity/factor VIII-related antigen ratio when compared to that of 55 normal subjects. It is suggested that an elevated factor VIII activity/factor VIII-related antigen ratio may be used for detection of the carriers of von Willebrand's disease.
TL;DR: It is indicated that platelets are damaged in vitro when exposed to amounts of blue light used in phototherapy, similar to that used in neonatal hyperbilirubinemia.
Abstract: Phototherapy with blue fluorescent light is widely employed for treatment of neonatal hyperbilirubinemia. Functional, biochemical, and morphologic changes produced by blue fluorescent light in human platelets were identified and characterized. Platelet-rich plasma was exposed for up to 170 min to amounts of light equivalent to that used in phototherapy of neonatal hyperbilirubinemia. Within 110 min of light exposure, platelets were essentially no longer aggregable by ADP and connective tissue suspension and were depleted of ADP, ATP, and glycogen. Electron photomicrographs revealed these platelets to be swollen, depleted of glycogen granules and organelles, and to have ill-defined membranes. Platelet injury could be accelerated by adding a photosensitizing agent, hematoporphyrin, to platelet samples before exposure. In contrast, control platelets kept in the dark for 170 min or nonirradiated platelets resuspended in irradiated plasma maintained their integrity. The results indicate that platelets are damaged in vitro when exposed to amounts of blue light used in phototherapy.
TL;DR: It was found that an elevated VIII‐ratio is a very sensitive indicator of intravascular coagulation and the amount of factor VIII‐related antigen remained the same or was even increased when measured by agarose quantitative immunoelectrophoresis.
Abstract: The relationship between factor VIII (AHF) procoagulant activity and factor VIII-related antigen were examined in patients with disseminated intravascular coagulation (DIC), pulmonary embolism (PE), and coronary artery disease with or without myocardial infarction (MI). It was found that 13 of 13 patients with DIC, 17 of 17 patients with PE, and 10 of 12 patients with MI possessed a significantly elevated factor VIII-related antigen to factor VIII activity ratio (VIII-ratio). The VIII-ratio returned to normal in each of 2 patients with DIC and 1 paitent with PE after treatment with heparin, heparin and alpha-amino-caproic acid, and heparin and coumadin respectively. In contrast, the VIII-ratio was slightly elevated only in 1 of 15 patients with coronary artery insufficiency without MI. In in vitro studies, after treatment of plasma with thrombin or plasmin, factor VIII activity was lost, whereas the amount of factor VIII-related antigen remained the same or was even increased when measured by agarose quantitative immunoelectrophoresis. These observations have led us to conclude that an elevated VIII-ratio is a very sensitive indicator of intravascular coagulation.