bluuebunny/crossref_metadata_2025 huggingface dataset:
Organ distribution and fate of human platelets: Studies of asplenic and splenomegalic patients
Authors: Hill‐Zobel Robin L. , McCandless Brian , Kang S. Andrew , Chikkappa Gundabhaktha , Tsan Min‐Fu
Published: February 2007

Little is known about the organ distribution and fate of human platelets. We investigated the kinetics, organ distribution, and fate of autologous 111 In‐oxine‐labeled platelets in 12 normal volunteers, four asplenic subjects, and four patients with splenomegaly.

The initial recovery of infused 111 In‐platelets from the circulation was 97.8 ± 9.8% (means ± SD) for asplenic subjects and 26.3 ± 5.9% for splenomegalic patients as compared to 59.2 ± 9.3% for normal controls. The mean platelet survival times as derived from the multiple‐hit model were 9.2 ± 1.0 days for asplenics and 6.2 ± 0.6 days for splenomegalic subjects (8.4 ± 0.8 days for normals).

At 30 min postinfusion, 79.4 ± 19.2% of the infused 111 In‐platelets pooled in the spleen of splenomegalic subjects and 42.7 ± 12.2% in normal controls. There was 7.1 ± 2.0, 12.6 ± 3.7, and 29.3 ± 8.4% pooling in the liver of splenomegalic, normal, and asplenic subjects, respectively. At 10 days postinfusion, 37 and 24% of the 111 In‐platelets were sequestered in the spleen and liver of normal control subjects, respectively. Similar figures for splenomegalic subjects were 71 and 14%, respectively. In asplenic subjects, 89% was sequestered in the liver.

We conclude that spleen and liver are the primary sites of platelet destruction, accounting for 61% of infused 111In‐platelets in normal volunteers and 85% in splenomegalies, while the liver is the primary site of platelet destruction, accounting for 89% in asplenic subjects.
Spectrum of HTLV‐III infection in a hemophilic cohort treated with blood products from a single manufacturer
Authors: McGrath Katherine M. , Spelman Denis , Barnett Mark , Kellner Sybil
Published: February 2007

One hundred fifty‐eight hemophilia A, B, and von Willebrand disease (VWD) patients treated with clotting factor concentrates from a single manufacturer were tested for antibody to the human T‐lymphotropic virus type III (HTLV‐III). Antibody was detected in 63% and 40% of those with severe hemophilia A and B, respectively 12% and 0% of those with mild hemophilia A and B, and two patients with recessive VWD. Forty‐two antibody‐positive and 20 antibody‐negative patients were studied for clinical and laboratory features of infection. Eleven seropositive patients had clinical signs of infection including Pneumocystis carinii pneumonia, lymphadenopathy, splenomegaly or diarrhea; however, only one patient had developed acquired immune deficiency syndrome (AIDS), and only two had significant impairment of their performance status. Thirty‐one patients remained totally asymptomatic. Eight patients had a history suggestive of acute HTLV‐III infection. Thrombocytopenia was observed in 18% of seropositive patients, lymphopenia in 60%, depressed T‐helper cells in 43%, reduced T‐helper: T‐suppressor ratios (TH: TS) in 33%, and elevated platelet‐bound immunoglobulin in 53%. The antibody‐negative group had normal T‐helper cell levels (except one patient) and TH: TS ratios, and normal platelet immunoglobulin levels. Both groups demonstrated a significant elevation of immunoglobulin levels and a high prevalence of antinuclear factor and antismooth muscle antibodies. The mean level of IgG was significantly higher in the antibody‐positive group. This study confirms the correlation between HTLV‐III infection and reduced T‐helper cells in hemophiliacs but demonstrates a low incidence of clinical symptomatology. There was evidence of polyclonal B‐cell hyperactivity in the antibody‐negative group as well as the seropositive group.
Characterization of purine nucleoside phosphorylase in leukemia
Authors: Morisaki Takayuki , Horiuchi Naomi , Fujii Hisaichi , Miwa Shiro
Published: February 2007

Purine nucleoside phosphorylase (PNP) activity was determined in mononuclear cells from 49 patients with various types of leukemia. A low level of PNP activity was found in mononuclear cells from patients with acute myeloid and lymphoblastic leukemia and with chronic lymphocytic leukemia. Enzymatic and immunological studies on PNP from leukemic cells of these patients revealed no differences in Michaelis constant for inosine, thermostability, electrophoretic mobility, immunological reactivity, or specific activity between the PNP of leukemic cells and that of normal mononuclear cells. These results suggest that the decrease in PNP activity of leukemic cells is due to a decreased rate of enzyme synthesis. Thus, the abnormality of PNP activity might be due to an alteration in the regulatory mechanism of enzyme synthesis in the purine metabolism in the leukemic clone.
Human parvovirus and aplastic crisis in chronic hemolytic anemias: A study of 24 observations
Authors: Lefrère Jean‐Jacques , Couroucé Anne‐Marie , Bertrand Yves , Girot Robert , Soulier Jean‐Pierre
Published: February 2007

From March 1984 through November 1985, 24 children and adults with aplastic crises were admitted in several Parisian hospitals. Twelve patients had known hemolytic anemia. Aplastic crisis revealed hemolytic anemia in the remaining patients. The detection of human parvovirus antigen was performed by counter‐immunoelectrophoresis, and specific IgM antibodies were detected by IgM‐antibody‐capture‐radioimmunoassy, in order to establish the incidence of human parvovirus infection in the genesis of the aplastic crisis. Twenty‐one patients had acute infection with human parvovirus. In the three remaining patients, no marker of human parvovirus infection was found. The features of the human parvovirus linked aplastic crisis are described. We consider that human parvovirus infection, and unknown hemolytic anemia, must be systematically researched in any case of unexplained acute aplastic anemia.
Is sickle cell crisis a thrombotic event?
Authors: Green David , Scott John Paul
Published: February 2007

Although large vessel thrombi are occasionally reported in patients with homozygous sickle cell disease, the role of intravascular coagulation in typical pain crises is controversial. Therefore, we studied 24 sickle cell patients during and between episodes of pain crisis, using several sensitive tests of hemostasis. Fibrinogen was measured by a clotting assay, β3‐thromboglobulin (β‐TG) and fibrinopeptide A (FPA) were quantitated by radioimmunoassay, and protein C was determined by absorbing the zymogen from test plasma, activating it with thrombin‐thrombomodulin complex, and measuring activity with a selective synthetic substrate. Fibrinogen was elevated in asymptomatic patients (355 ± 145 mg/dl) but was no different from the value in these same patients during crisis (333 ± 180 mg/dl, p > 0.1). Similarly, β‐TG 136 ± 52 ng/ml vs 118 ± 56; FPA 3.7 ± 4.8 ng/ml vs 5.2 ± 4.5, and protein C 71 ± 20% vs 66 ± 19 showed no important changes during crisis. However, all these values were significantly different from those in age‐ and sex‐matched healthy controls. (β‐TG, fibrinogen, and FPA were elevated (p < 0.001, 0.005, and 0.05, respectively), and protein C was decreased (p < 0.003). We conclude that while chronic intravascular coagulation is common in patients with sickle cell disease, there is no evidence that the pain crisis per se is a thrombotic event.
Intravenous gammaglobulin (Gamimune) for treatment of chronic idiopathic thrombocytopenic purpura (ITP): A two‐year follow‐up
Authors: Warrier Indira A. , Lusher Jeanne M.
Published: February 2007

Thirteen subjects 5‐20 years of age with the chronic, autoimmune form of idiopathic thrombocytopenic purpura (ITP) were given intravenous gammaglobulin (Gamimune; Cutter Biological, Berkeley, CA) in a dose of 400 mg/kg per day for 5 consecutive days. Two of the 13 children had undergone splenectomy; the other 11 had not. Eight of these 13 children had also received corticosteroid therapy with no sustained increase in platelet of counts. Six of 13 children had a good or excellent response to the first 5 day course of gammaglobulin therapy, and one had a fair response. The peak platelet count occured within 7 days of the start of therapy except in one patient, whose platelet count peaked on day 12. Six of seven patients who initially responded to Gamimune required booster doses to maintain platelet counts at a safe level. All children had marked increases in serum IgG following Gamimune except one (who had undergone splenectomy for chronic ITP), who had high baseline levels of immunoglobulin G (IgG). No untoward reactions necessitating cessation of therapy were encountered during this study. The most common side effect observed was headache. During the first year of follow‐up after Gamimune, three of seven initial responders became refractory to Gamimune therapy. Two of these three refractory subjects later underwent splenectomy with excellent response. The third refractory patient who was splenectomized prior to gammaglobulin therapy had spontaneous remission of his ITP 5 months after the last dose of Gamimune. Three of the four other initial responders have continued to do well and have maintained platelet counts above 40,000/mm3 (one without booster). The fourth subject dropped out of the study. Thus our observations indicate that Gamimune is an effective form of treatment for some children with chronic ITP, and can be considered as an alternative to splenectomy or as a potential therapeutic modality in those who have failed to respond to splenectomy.
Efficacy of danazol in pure red cell aplasia
Authors: Lippman Scott M. , Durie Brian G. M. , Garewal Harinder S. , Giordano Gerald , Greenberg Bernard R.
Published: February 2007

Twenty‐one unselected patients with refractory chronic anemias of various etiologies were treated with danazol, a synthetic attenuated androgen. All had previously failed treatment with hematinics, androgens, corticosteroids, high‐dose intravenous immunoglobulin, antithymocyte globulin, cytotoxic immunosuppressive agents, and/or plasmapheresis. Three patients with pure red cell aplasia and one with aplastic anemia responded. No responses were observed in 11 patients with myelodysplastic syndromes, two patients with myelofibrosis, and two with paroxysmal nocturnal hemoglobinuria. Remission in pure red cell aplasia was maintained with danazol alone in one patient and required combined low‐dose prednisone in two. Objective responses occurred in 2 to 3 weeks and therapy generally was well tolerated. To date, one patient with pure red cell aplasia remains in complete remission at 9 months on lowdose danazol alone. We conclude that danazol alone or combined with prednisone may induce and maintain remission in severe refractory pure red cell aplasia and possibly other chronic cytopenias characterized by immunologic marrow suppression. Further trials of danazol in treating these disorders are indicated.
Acute leukemia with t(4;11) following treatment for breast cancer
Authors: Archimbaud Eric , Charrin Christiane , Sebban Catherine , Fiére Denis
Published: February 2007

We report the case of a 51‐year‐old woman presenting t(4;11) acute undifferentiated leukemia 19 months after initiation of adjuvant radio‐chemotherapy for a breast cancer. Morphology of the blasts was FAB L2 and cytochemical and immunological studies were in favor of an undifferentiated leukemia. A possible relationship between t(4;11) leukemia and exposure to carcinogens is discussed.
Evaluation of the nature of mildly prolonged prothrombin times
Authors: Mazzucconi M. G. , Mariani G. , Chistolini A. , Lasagni R. Pasquali , Motta M. , Ghirardini A. , Altieri D. , Mannucci P. M. , Mandelli F.
Published: February 2007

Twenty‐one asymptomatic individuals with a mildly prolonged prothrombin time ( > 2 SD from the prothrombin time of the reference plasma) were found to have a mild isolated factor VII (F VII) defect (x 38.8 U/dl; SD 13.2). Factor VII antigen levels were also found to be reduced (x 45.5 U/dl; SD 7.8) in 13 of them. These figures were compared with those of 50 normals and 28 obligatory heterozygotes for F VII deficiency. The phenotypical behaviors in the propositi were found to be equal to those of the F VII congenital deficiency heterozygotes: the discrepant one (VII+) and the nondiscrepant one (VII−/R).

Fifteen families of the propositi could also be studied, totalling 55 additional individuals; in 25 of them (ten pedigrees) a mild F VII deficiency was found showing the same phenotypical features of the corresponding propositi.

We therefore believe that these individuals with mild F VII deficiency can be considered as heterozygotes for the defect, since (1) the other vitamin K‐dependent clotting factors were normal; (2) the defect is transmitted throughout the kindred with the same mode of inheritance as F VII congenital deficiency; and (3) F VII: C and F VII:Ag levels are highly comparable with those of known obligatory heterozygotes for F VII deficiency.

On the grounds of a careful statistical analysis we propose a formula which allows a discrimination between the two phenotypes of the heterozygotes for F VII congenital deficiency.

In addition it is suggested that sensitive tissue thromboplastins should be used to pick up these mild defects.
Functional analysis of the marginating pool of human polymorphonuclear leukocytes
Authors: Berkow Roger L. , Dodson Robert W.
Published: February 2007

The intravascular pool of human polymorphonuclear leukocytes (PMN) is composed of one compartment which is circulating and another that is marginated to the vascular endothelium. Administration of B‐adrenergic agonists leads to a rapid demargination with an increase in the circulating PMN pool. The marginating PMN has previously been stated to represent an older PMN based on a higher cytochemical alkaline phosphatase activity. With the understanding that circulating PMN are heterogeneous with respect to function and size we undertook the present study to evaluate the contribution of the marginating PMN to functional and volume‐dependent heterogeneity. We found that PMN isolated 7 min after epinephrine administration, presumably enriched by marginating PMN, were not different in volume, biochemically measured alkaline phosphatase activity, stimulated superoxide anion release, degranulation, or phagocytosis. These data suggest that the circulating and marginating pools of PMN are interchangeable and that the marginating PMN are not enriched by a particular subpopulation of PMN.
Search for eosinopenia in hospitalized patients with normal blood leukocyte concentration
Authors: Krause John R. , Boggs Dane R.
Published: February 2007

Hospitalized patients were studied prospectively in an attempt to determine whether idiopathic eosinopenia in the absence of other major changes in blood cells is rare or is more frequent than is commonly recognized. Strict criteria for eosinopenia were used; patients with more than 10.0 × 109/liter total leukocyte count, or less than 4.0, as well as those with any form of hematologic cancer, or those receiving any form of cancer chemotherapy, were excluded from the study. With those criteria and exclusions, only 24 patients with eosinopenia were found among 24,300. Twenty were receiving some form of adrenal glucocorticosteriod (steroid) and of the other four, three had serious organic diseases for which they were receiving various drugs. The remaining patient, whose primary problem was depression, could have had druginduced eosinopenia. Thus, unexpected eosinopenia appears to be a very rare event or syndrome.

A normal range for eosinophils was defined from studies of 740 medical students, which was 0.015 to 0.65 × 109/liter and was quite similar to previously reported values. The effect of acute or chronic steroid administration on eosinophils in normal human subjects was studied. Confirming studies reported for man and many other mammals, eosinopenia developed promptly, but disappeared within hours unless repeated doses were given. Literature on various types of eosinopenia was reviewed.
Role of immune stimulation in the etiology of multiple myeloma: A case control study
Authors: Cohen Harvey Jay , Bernstein Rosyln Julie , Grufferman Seymour
Published: February 2007

As hospital‐based case‐control study of 153 multiple myeloma (MM) cases and 459 controls was conducted to evaluate the hypothesis that chronic or frequent infections or allergic and autoimmune diseases might be of higher prevalence in individuals who develop MM. Information was obtained by direct interviews of subjects. Controls were matched to cases on age, sex, race, and hospital. “Immune‐stimulating conditions” included chronic infections such as pyelonephritis, urinary tract infections (UTIs), prostatitis, rheumatoid arthritis and other collagen vascular diseases, allergies, bronchitis, tuberculosis, cholecystitis, diverticulitis, and osteomyelitis. The overall odds ratio (OR) (odds of history of immune‐stimulating conditions in cases versus controls) was 0.4 (95% confidence interval = 0.3 − 0.7) which suggested that cases had significantly less immune‐stimulating conditions than did controls. The exposure rate for these conditions was high for cases (0.7) as well as for all control groups (0.8). These findings suggest that immune‐stimulating conditions alone are not the causative factor in the etiology of MM, though they may play a role in the predisposed individual.
Effects of zinc supplementation on linear growth in beta‐thalassemia (A new approach)
Authors: Arcasoy A. , Çavdar A. , Cin Ş. , Erten J. , Babacan E. , Gözdasoglu S. , Akar N.
Published: February 2007

Linear growth was evaluated in 32 patients with beta‐thalassemia major. At the beginning of the study of 40.6% of the patients were below the 10th percentile with biochemical evidence of zinc deficiency. Effects of zinc supplementation on growth velocity (height) were assessed in a controlled manner. Twenty‐one children received oral zinc sulphate for a period of 1 to 7 years (15 early‐ and 6 late‐supplemented cases), while the remaining 11 thalassemics were maintained only on conventional transfusion therapy. The mean height velocity of early‐zinc supplemented children was significantly greater than that of normal children (P < 0.01). An increase in height was also observed in the patients who received delayed zinc retardation. The present study demonstrated that zinc deficiency is one of the factors responsible for retarded linear growth in beta‐thalassemia major. Only the patients who received zinc supplementation showed an acceleration of growth in height. Administration of zinc could, therefore, be considered as an effective adjuvant therapy in homozygous betathalassemia.
Effect of alpha interferon on the altered t‐b‐cell immunoregulation in patients with thalassemia major
Authors: Nualart Patricia , Estevez Maria E. , Ballart Isidro J. , De Miani Susana A. , Peñalver Jorge , Sen Luisa
Published: February 2007

We studied the ability of B‐lymphocytes to differentiate to immunoglobulin‐producing cells in 14 patients with thalassemia major, 11 parents of the patients, and 86 normal subjects. In comparison with the parents of the patients and with the normal individuals, the patients were found to have 1) an increased number of cells spontaneously secreting immunoglobulin; 2) a decreased number of plaque‐forming cells (PFC) when induced with pokeweed mitogen (PWM) and a deficient helper T‐cell function for the induction of B‐cell differentiation; 3) an increase in the number of PFC after the addition of alpha interferon (100 IU/ml) to the cell cultures with PWM. Previous incubation of non‐T‐cells with alpha interferon for 1 hr and subsequent coculture with T‐cells from the same patients or from normal subjects in the presence of PWM increased the number of PFC. On the contrary, previous incubation of T‐cells with alpha interferon followed by coculture with normal non‐T‐cells or cells from the same patient did not modify the number of PFC.

These results suggest that patients with thalassemia major possess hyperreactive spontaneous B‐cell responses and that these B‐cells are unable to differentiate to immunoglobulin‐secreting cells in the presence of PWM. This would be due to a T‐helper‐cell deficiency with an inability to produce lymphokines (interferon being one of them), while the B‐cell function seems to remain intrinsically intact.
Natural history of acquired immunodeficiency syndrome in hemophilic patients
Authors: Kim Hugh C. , Nahum Kenneth , Raska Karel , Gocke David J. , Kosmin Martin , Karp George I. , Saidi Parvin
Published: February 2007

During the 5‐year period from 1981 to 1985, we have observed 8 cases of acquired immunodeficiency syndrome (AIDS) among our 85 patients with hemophilia A. Thus, the prevalence of AIDS with hemophilia A is 9.4% in our patient population. By utilizing stored serum or plasma samples dating back to 1978, antibody against HTLV‐III was detected in all 8 cases with AIDS. Based on the time interval from the appearance of antibody to HTLV‐III to the diagnosis of AIDS in these patients, the incubation period ranged from 27 months to 60 months, with a median of 36 months. Before the diagnosis of full‐blown AIDS, all patients exhibited a variety of prodromal manifestations of non‐specific nature, including weight loss, oral candidiasis, unexplained non‐productive chronic cough, generalized lymphadenopathy, and thrombocytopenia lasting several months to several years. Serial T‐lymphocyte subset studies were available in some patients during the HTLV‐III seropositive period and showed progressive lymphopenia, depletion of T4 cells with an average absolute count of 94 ± 128 per mm3 (mean ± 1 S. D.), and a markedly reversed T4/T8 ratio of 0.26 ± 0.19 (mean ± 1 S. D.). These findings suggest that the incubation period of AIDS is considerably long and that prospective study of serial immunologic markers and HTLV‐III markers may be warranted in hemophilic patients at risk.
Immunogold staining of microtubules in resting and activated platelets
Authors: Escolar Gines , Sauk John , Bravo Maria Luisa , Krumwiede Marlys , White James G.
Published: February 2007

A circumferential microtubule is known to support the discoid form of resting platelets, but its fate following exposure of the cells to aggregating agents is uncertain. The present study has employed an immunocytochemical approach to follow the fate of the circumferential microtubule in activated platelets. Monoclonal antibodies to tubulin and to vinculin and a polyclonal antibody to actin were incubated with isolated microtubule coils and stained with staphylococcal protein A coupled to immunogold in order to test their specificity. Thin sections of glycolmethacrylate embedded platelets before and after exposure to thrombin for 15, 30 and 60 s were stained with antibodies to tubulin and actin. Immunogold particles showed a high specificity for isolated MT coils stained for tubulin, modest intensity for actin, and none for vinculin. Gold particles were randomly distributed in thin sections of resting and activated platelets stained for actin. Immunogold was limited to the circumferential microtubule in resting platelets and constricted coils in thrombin‐activated cells. The number of gold particles in areas of cytoplasm away from microtubules in platelets stained with antitubulin antibody increased slightly following thrombin activation, but the change was not significant. Results support the concept that microtubule coils supporting the discoid form of resting platelets do not dissolve following exposure of the cells to potent agonists.
Discordance in a pair of identical twin carriers of factor IX deficiency
Authors: Kitchens Craig S.
Published: February 2007

Female twin daughters of a man with hemophilia B were determined to be identical but widely discordant with respect to their degree of factor IX deficiency. The proposita had a marked deficiency (3%) of factor IX with clinical bleeding. She became pregnant. Delivery was managed with infusion of factor IX concentrates. These twins represent the second reported case of identical twins with discordant factor IX levels.
Combination of three α‐globin gene loci deletions and hemoglobin new york results in a severe hemoglobin H syndrome
Authors: Chan Vivian , Chan T. K. , Tso S. C. , Todd D.
Published: February 2007

A Chinese patient with hemoglobin (Hb) H and Hb New York is described. Unlike classical Hb H disease, the additional βNew York chain defect resulted in a more marked α β 3‐globin chain imbalance in this patient with only one α‐gene, accounting for her severe anemia (3.4‐6.8 g/dl) during the steady state.
Acute lymphocytic leukemia: Correlation of clinical features with immunocytochemical classification
Authors: Twu Bair‐Her , Li Chin‐Yang , Smithson William A. , Clark Hoagland H. , Dewald Gordon W.
Published: February 2007

Many immunologic studies of acute lymphocytic leukemia (ALL) during the past decade have demonstrated the close correlation of immunologic phenotypes of ALL subclasses with the clinical presenting features and prognosis. However, the clinical application of conventional immunologic techniques had been very limited because of the requirement of a fresh sample to prepare the mononuclear cell suspensions for study. We studied 81 cases of ALL using immunoperoxidase stain for nuclear terminal deoxynucleotidyl transferase (TdT) and immunoalkaline phosphatase stain for surface markers (using monoclonal antibody J5 for common ALL antigen [CALLA], Leu‐1 for pan‐T antigen, and B1 for pan‐B antigen) on air‐dried smears. The cases were classified as common ALL (TdT+, CALLA+, pan‐T−, and pan‐B−) (41 cases), null‐ALL (TdT+, CALLA−, pan‐T−, and pan‐B−) (19 cases), T‐ALL (TdT+, CALLA−, pan‐T+, and pan‐B−) (nine cases), B‐ALL (TdT−, CALLA−, pan‐T−, and pan‐B+) (six cases), pre‐B‐ALL (TdT®, CALLA+, pan‐T−, and pan‐B+) (four cases), or pre‐T‐ALL (TdT+, CALLA+, pan‐T+, and pan‐B−) (two cases). This subtyping of ALL correlated well with known clinical presenting features, prognosis, chromosome analysis in 35 cases with an abnormal clone, and conventional immunologic typing in 38 cases. The data suggest that these simple and practical immunocytochemical stains can be used for immunologic subclassification of ALL.
Corticosteroids therapy in paroxysmal nocturnal hemoglobinuria
Authors: Issaragrisil Surapol , Piankijagum Anong , Tang‐naitrisorana Yaowalak
Published: February 2007

We evaluated the efficacy of alternate day, high dose prednisolone for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). Nineteen patients were included. Thirteen were men and six were women, aged between 13–56 years. Eleven patients improved, eight with good response and three with fair response. Eight patients were non‐responders. Responders had gradual improvement in the hemoglobin level, but none achieved a normal hemoglobin level. Age at diagnosis, sex, initial hemoglobin, white count, and percentage of a positive Ham's test had no apparent bearing on treatment outcome. A prolonged interval from diagnosis to prednisolone treatment decreased the chance of a favorable hematologic response to therapy. Age at the treatment in non‐responders was higher than responders. Responders had higher numbers of colonies derived from BFU‐E and CFU‐GM both in the blood and bone marrow than non‐responders although the differences did not achieve statistical significance. These data indicate that alternate day, high dose prednisolone therapy is effective in some patients with PNH.
Spontaneous antithrombin in a patient with benign paraprotein
Authors: Gabriel Don A. , Carr Marcus E. , Cook Linda , Roberts Harold R.
Published: February 2007

A 66‐year‐old man with peptic ulcer desease developed a paraprotein that resulted in a spontaneously prolonged prothromoin time, activated partial thromboplastin time, and thrombin clotting time. Although the reptilase time was normal, the thrombin clotting time failed to correct with the addition of normal plasma, calcium, or protamine sulfate. The patient's purified fibrinogen was normal, but his serum contained an IgG that inhibited the clotting of normal plasma and purified fibrinogen in the presence of thrombin. In contrast to previously described paraproteins, this patient's IgG appeared to inhibit the activity of thrombin per se rather than to interfere with fibrinogen cleavage or fibrin polymerization. Although immunoprecipitation between thrombin and the paraprotein could not be demonstrated, the patient's purified IgG, in the presence of thrombin, decreased the thrombin activity on a chromogenic substrate. Further, increasing concentrations of thrombin overcame the inhibitory effect of the patient's paraprotein. Thus, the patient's paraprotein appeared to possess antithrombin activity.
Impaired synthesis of immunoglobulin in patients with chronic lymphocytic leukemia
Authors: Kurec Anthony S. , Davey Frederick R.
Published: February 2007

The cause of hypogammaglobulinemia in patients with chronic lymphocytic leukemia (CLL) is unknown. Experiments were performed to determine if sera, monocytes, or non‐T cells from patients with CLL suppress the proliferative response and synthesis of immunoglobulin (Ig) following incubation with pokeweed mitogen (PWM) in cocultures with lymphocytes from normal individuals. The data indicate that sera and monocytes from patients with CLL did not suppress the proliferative response or synthesis of Ig by normal non‐T cells. When various numbers of normal non‐T cells and CLL non‐T cells were cocultured with a constant number of normal T cells, the proliferative response and the concentration of supernatant Ig decreased as the proportion of CLL non‐T cells increased. Since similar results were obtained when irradiated non‐T cells from normal individuals were substituted for non‐T cells from patients with CLL, we believe that the decrease in proliferative response and diminished synthesis of Ig is not the result of the suppressor non‐T cells but is related to the dilution of normal B cells by inert non‐ T cells. We conclude that these experiments serve as an in vitro model for patients with CLL and suggest that the hypogammaglobulinemia observed in this disease is related to the diluting out of normal B cells by the accumulation of neoplastic B cells in the peripheral blood, bone marrow, and lymphoid tissue of these patients.
No evidence for bradykinin hydrolysis in human erythrocyte suspensions: H NMR studies
Authors: Hyslop Serena J. , King Glenn F. , Kuchel Philip W.
Published: February 2007

In view of their permeability to small peptides, it has been postulated that human erythrocytes may play a role in terminating the action of some circulating peptide hormones. Work using classical paper chromatographic techniques for detecting free amino acids indicated that the octapeptide, des‐(Arg9)‐bradykinin, enters these cells and its amino‐terminal arginine residue is released by cytosolic aminopeptidase‐P. We have used 1H NMR to monitor directly the release of arginine from bradykinin. The hydrolytic reaction rate in hemolysates, with an initial peptide concentration of 13.0 mmol l−1 was 6.5 mmol (1 packed red cell)−1h−1. But no reaction was evident after a 4.5‐h incubation with intact cells, thus contradicting the earlier suggestion that erythrocytes are involved in the primary inactivation of this hormone. This is consistent with our previous findings that the pentapeptide leu‐enkephalin fails to enter human erythrocytes but that its lower‐order degradation products may do so.
Differentiation between essential thrombocythemia and polycythemia vera with marked thrombocytosis
Authors: Iland Harry J. , Laszlo John , Case Delvyn C. , Murphy Scott , Reichert Thomas A. , Tso C. Y. , Wasserman Louis R.
Published: February 2007

Accurate distinction between essential thrombocythemia and thrombocytotic polycythemia vera requires determination of the red cell mass in the presence of adequate iron stores, but this is not always possible. We therefore compared the clinical and laboratory features at the time of presentation of 50 patients with unequivocal essential thrombocythemia and 27 patients with thrombocytotic polycythemia vera. Univariate analysis failed to identify any single parameter capable of reliably separating the groups. A logistic regression algorithm incorporating hematocrit, white cell count, and spleen size markedly increased the diagnostic accuracy (92 %) compared with predictions based on the hematocrit alone (52 %). The algorithm's usefulness for patients with intermediate hematocrits was confirmed by analysis of independent samples of essential thrombocythemia and thrombocytotic polycythemia vera patients, and also by analysis of patients with probable essential thrombocythemia in whom the diagnosis could not be confirmed because of inadequate exclusion of polycythemia vera. Furthermore, comparison of survival data suggests that differentiating these disorders is prognostically important. The algorithm is recommended as an alternate method for differentiating essential thrombocythemia from thrombocytotic polycythemia vera whenever the red cell mass is unavailable or iron deficiency cannot be excluded.
Measurement of terminal deoxynucleotidyl transferase mrna in clinical samples: A new parameter in analysis of leukemia cells
Authors: Wolf Susan C. , Steinherz Peter G. , Landau Nathaniel R. , Silverstone Allen E.
Published: February 2007

A 1750 base pair cDNA to human terminal deoxynucleotidyl transferase (TdT) has been cloned. This cDNA detects a dominant 2200 base pair messenger RNA species in normal and leukemic cells synthesizing the enzyme. A quantitative dot blot assay was utilized to survey a number of clinical samples from patients with TdT positive and negative leukemias as well as cells from normal volunteers. A linear relationship was detected between the amount of TdT mRNA and the amount of enzyme activity in bone marrow cells. The assay is sensitive enough to detect normal TdT levels in bone marrow, and distinguish these levels from the lack of such mRNA in peripheral blood and bone marrow of patients with myeloid leukemia. Elevated levels of mRNA were found in two cases of patients in clinical remission. The prognostic significance of these observations must await further study.
Two murine monoclonal antibodies to peripheral blood monocyte differentiation antigens discriminate within M5 acute non‐lymphoid leukemia (ANLL) cells
Authors: Lopez M. , De Rossi G. , Santoro L. , Mandelli F. , Alescio T. , Annino L. , Pasqualetti D. , Siccardi A. G. , Mottolese M. , Natali P. G. , Cuomo M.
Published: February 2007

Two murine monoclonal antibodies (MoAbs), LAM3 and LAM7 of the IgG1 isotype, which were produced by immunization with normal peripheral blood monocytes (PBM), were assayed in their specificity by indirect immunofluorescence against a panel of normal as well as leukemic cells.

Both LAM3 and LAM7 were reactive with PBM while LAM3 also recognized platelets. Neither MoAb showed reactivity with erythrocytes, granulocytes, or resting and mitogen activated B and T lymphocytes. The reactivity with bone marrow cells correlated with the degree of monocyte contamination.

Among the 62 cases of leukemia tested, which included three cases of B‐CLL, 19 cases of ALL, and 40 cases of ANLL, both MoAbs reacted highly homogenously only with M5b ANLL cells. These findings indicate that the two MoAbs, which recognize two distinct epitopes, represent useful markers in the differential diagnosis of M5b ANLL.
Apotransferrin receptors and the delivery of iron from cultured human blood monocytes
Authors: Baynes R. D. , Bukofzer G. , Bothwell T. H. , Bezwoda W. R.
Published: February 2007

A study was done to find out whether apotransferrin receptors are involved in the release of iron from reticuloendothelial cells. To this end, human macrophages which had been obtained by culturing blood monocytes for 7 days were incubated with either diferric or apotransferrin at the physiological pH of 7.4 or at an acidic pH (6.0). While specific diferric transferrin receptors (Kb 1.3 × 10−8M) were demonstrated at pH 7.4, no apotransferrin receptors were found. In contrast, both diferric receptors (Kd 2.1 × 10−8M) and apotransferrin receptors (Kd 2.8 × 10−9M) were found at pH 6.0. The finding of specific apotransferrin binding at acidic pH fits in with the current understanding of iron uptake by cells, in which the iron‐transferrin complex is endocytosed and the iron is released at acidic pH. The present results suggest that the apotransferrin remains attached to its receptor in the endocytosed vesicle at this acidic pH but that it becomes detached at the cell surface where the pH is neutral. No evidence was found to indicate that iron is transported out of macrophages via apotransferrin receptors at the physiological pH.
Cryptococcal tonsillitis in a patient with chronic lymphocytic leukemia: An unusual manifestation of cryptococcal disease
Authors: Korvick Joyce , Yu Victor L.
Published: February 2007

We present a case of chronic tonsillitis in a patient with chronic lymphocytic leukemia. Despite empiric radiation and antibiotic therapy, the patient's sore throat and tonsillar enlargement persisted. Excisional biopsy of the involved tonsil revealed the presence of Cryptococcus neoformans. Blood cultures also yielded cryptococcus. Specific antifungal therapy resulted in cure. To knowledge our this is the first case report of cryptococcal infection of the tonsil. This case illustrates the pitfalls of empiric therapy in an immunosuppressed host.
Systemic necrotizing vasculitis in sickle cell disease
Authors: Manci Elizabeth A. , Maisel Deborah A. , Conrad Marcel E.
Published: February 2007

A patient with sickle cell disease and systemic necrotizing vasculitis is reported. Although there are a number of immune defects in patients with sickle cell disorders, this association has not been previously reported. We suspect that immunologic disorders frequently are unrecognized in these patients because the symptoms are attributed to complications of sickle cell disease.
Osteonecrosis in a patient with immune thrombocytopenic purpura
Authors: Smith Roy E. , Chelmowski Mark K. , Anderson Tom
Published: February 2007

We report a case of osteonecrosis in a 26‐year‐old woman treated with prednisone for immune thrombocytopenic purpura. The unusual complication occurred after a much shorter course of steroids of a considerably smaller cumulative dose than in previously reported cases.
Acquired von willebrand disease in patients with polycythemia rubra vera
Authors: Mohri Hiroshi
Published: February 2007

Platelet function and factor VIII complex were evaluated in ten patients with polycythemia rubra vera. Seven patients showed abnormal epinephrine‐induced aggregation. The intracellular concentrations of adenosine diphosphate (ADP) were below normal, and the ratio of adenosine triphosphate (ATP)/ADP was greater than normal. In four of eight cases, there was a decrease in ristocetin cofactor activity and a reduction in the slowly migrating forms of vWF:Ag on crossed immunoelectrophoresis. Defect of large multimers of vWF:Ag was also observed. The ratio of vWF:Ag to ristocetin cofactor was elevated in these patients. Plasma from the patients had no effect on normal plasma except in one case, in which isolated IgG appeared to cause inactivation of ristocetin cofactor. Treatment with 1‐deamino‐8‐arginine vasopressin caused correction of the vWF abnormalities with rapid return of ristocetin cofactor to baseline in some patients. The present study shows that the alterations of multimeric structure of vWF occur in more than 50% of patients with polycythemia rubra vera and are in some part due to the inhibitor specific for vWF.
Surgery in acute leukemia: A review of 167 operations in thrombocytopenic patients
Authors: Bishop J. F. , Schiffer C. A. , Aisner J. , Matthews J. P. , Wiernik P. H.
Published: February 2007

Of 435 consecutive patients with acute leukemia, 95 patients had 167 operations with a platelet count of < 100 × 109/L and 130 operations with platelet counts of < 50 × 109/L. Only 7% of operations had intraoperative blood loss of >500 ml, and 7% required >4 units of red cells transfused in the perioperative period. No patient died of bleeding attributable to surgery within 1 month of the operation. Granulocyte count was <0.5 × 109/L in 66% of operations with 57% febrile preoperatively. However, no patient developed infection within the surgical field in the postoperative month. Logistic regression analyses were used to assess preoperative factors, which identified those operations at risk for excessive bleeding or postoperative surgical complications. Major (group 1) operations, preoperative fever, and preoperative coagulation abnormalities were associated with operations with an intraoperative blood loss >500 ml and/or perioperative red blood cell RBC transfusions >4 units (P < .001). Surgery in cytopenic patients with acute leukemia is safe provided optimal supportive care is available.
Dissociation of neutrophil aggregation, adhesiveness, and Fc receptor activity
Authors: Spagnuolo Philip J. , Fain Mindy , Bass Steven N.
Published: February 2007

Neutrophils that bear receptors for the Fc portion of immunoglobulin G have been demonstrated to be more active in assays of adherence, aggregation, and chemotaxis compared to Fc receptor‐negative cells. We examined the relationship of neutrophil Fc receptor activity and cell–cell adherence or aggregation induced by phorbol myristate acetate. In contrast to 1‐isoproterenol, isobutyl‐methyl‐xanthine, and dibutyryl cAMP, each of which inhibited Fc receptor activity and neutrophil aggregation, theophylline significantly impaired aggregation without affecting Fc receptor activity. The selective beta‐2 agonist, metaproterenol, and 8‐Bromo cAMP failed to inhibit Fc receptor activity or neutrophil aggregation. Three known inducers of neutrophil intracellular cyclic AMP, PGE1, PGE2, and cholera toxin, also did not inhibit Fc receptor activity. Inhibition of Fc receptor activity by 95% in the presence of purified Fc fragments did not affect neutrophil aggregation. Similarly suppression of Fc receptor activity by purified Fc fragments did not inhibit neutrophil adhesion to nylon fiber columns. These data demonstrate that the Fc receptor does not mediate phorbol myristate acetate‐induced cell–cell adhesion and is not necessary for optimal neutrophil adhesion to nylon fibers. Our results are consistent with the possibility that the reversible inhibitory activity of beta‐adrenergic agonists on rosette formation may be a steric effect rather than a metabolic effect. These data tend to dissociate Fc receptor activity, neutrophil aggregation, and adhesion and support the hypothesis that the Fc receptor may be a marker of neutrophil heterogeneity rather than a component necessary for optimal neutrophil aggregation or adhesion.
Heme metabolism and in vitro erythropoiesis in anemia associated with hypochromic microcytosis
Authors: Brown A. C. , Lutton J. D. , Pearson H. A. , Nelson J. C. , Levere R. D. , Abraham N. G.
Published: February 2007

Heme metabolism and in vitro erythropoietic growth (CFU‐E, BFU‐E) were examined in bone marrow cells taken from two siblings with apparent familial hypochromic microcytic anemia. Bone marrow cells from both patients grew adequate numbers of CFU‐E and BFU‐E colonies in culture in the presence of erythropoietin. In addition, small numbers of endogenous CFU‐E were seen in 7‐day cultures. Assays on bone marrow cells taken from both patients revealed that baseline δ‐aminolevulinic synthase activity was considerably reduced, but increased six to seven fold (to normal levels) when patients' cells were exposed to pyridoxal phosphate (PLP). In both cases, ferrochelatase and δ‐aminolevulinic acid dehydratase activities were normal. Bone marrow heme oxygenase showed no significant differences in activities between normals and patients values in the absence or presence of PLP. In contrast, heme synthesis by patients' bone marrow was less than that of normals. This study demonstrates that bone marrow cells from patients with this rare disorder have some disturbances in heme metabolism, whereas erythropoiesis appeared to be normal when cultured with adequate nutrients in vitro.
Translocation (3;21) in Philadelphia chromosome—positive chronic myelogenous leukemia prior to the onset of blast crisis
Authors: Coyle Thomas , Najfeld Vesna
Published: February 2007

Two female patients in the chronic phase of CML were found to have, in addition to t(9;22), a new karyotypic abnormality—t(3;21)(q26;q22)—present in bone marrow cells. At diagnosis, this abnormality was observed in a small number of marrow cells in both patients, and as the disease progressed in patient 1, the percentage of cells showing t(3;21) was increased, reaching 100% as the transformation to blast crisis occurred. These observations suggest that t(3;21) may represent a new and rare nonrandom rearrangement which may be identified prior to the onset of blast crisis.
Immunogold staining in bone marrow aspirate for the study of surface markers in acute lymphoblastic leukemia
Authors: Penchansky Lila , Kaplan Sandra S. , Krause John R.
Published: February 2007

The diagnostic value of phenotyping acute lymphoblastic leukemia (ALL) of childhood using the immunogold staining method (IGS) was assessed in 34 consecutive new ALL patients seen at Children's Hospital of Pittsburgh during a 14‐month period. IGS proved to have considerable value in the diagnosis and classification of ALL. It allowed a sharp and clear identification of surface antigens, documented surface antigen heterogeneity in normal and abnormal cells, and provided a permanent record. The combination with cytochemistries allowed further cytoplasmic identification and correlation. This method does not require sophisticated equipment and can be performed in any laboratory, thus enabling results from different institutions to be more readily compared.
Influence of T lymphocytes on hematopoiesis in a patient with T cell hypoplasia
Authors: Hoffman Ronald , Lu Li , Jansen Jan , Bruno Edward , Brandt John , Boral Leonard , Cheung Killian
Published: February 2007

In this communication, we describe an unusual patient with a reported lifelong history of anemia. Investigation of the pathogenesis of this patient's bone marrow failure provided an interesting opportunity to determine the role of T cells in the regulation of human blood cell production. Phenotyping of the patient's mononuclear cells revealed severe T cell hypoplasia in both the peripheral blood and bone marrow. The patient's bone marrow was capable of producing 50–60% of the normal numbers of burst‐forming units—erythroid (BFU‐E) in the presence of optimal concentrations of erythropoietin, suggesting that marrow BFU‐E formation is in part independent of T cells. Addition of small numbers of class I identical donor T cells enhanced BFU‐E cloning efficiency to a level observed in normal controls. This enhancing effect was supplied by a T4+(CD4) population of donor cells. The addition of donor T cells partially corrected the inability of patient marrow cells to produce megakaryocyte and mixed colonies. These studies suggest that prolonged T cell hypoplasia might deprive marrow progenitor and stem cells of a necessary enhancing effect that is required for sustained normal hemato‐poiesis. Such a T cell defect in rare instances may result in bone marrow failure.
Dyserythropoiesis and erythroblast‐phagocytosis preceding pure red cell aplasia
Authors: Keefer Michael J. , Solanki Dilip L.
Published: February 2007

A 50‐year‐old woman with typical acquired primary pure red cell aplasia (PRCA) was successfully treated with prednisone. A later relapse was preceded by a period of ineffective erythropoiesis characterized by a reticulocyte response inappropriately low for the degree of anemia, serum iron of 189 üg/dl, total iron‐binding capacity (TIBC) of 213 μ/g/dl, and erythroid hyperplasia. In addition there was marked dyserythropoiesis and erythroblast‐phagocytosis. One month later, bone marrow examination showed classic PRCA. This rarely reported evolutionary stage of PRCA has several implications: 1) it suggests antibody induced erythroblast cytotoxicity as one mechanism of PRCA; 2) at a particular time in the development of PRCA there is potential for misdiagnosis as primary refractory anemia (PRA); and 3) some cases of PRA with similar morphologic and laboratory findings may be pathogenetically related to PRCA and may benefit from evaluation for immune‐mediated suppression of erythropoiesis.