bluuebunny/crossref_metadata_2025 huggingface dataset:
A new case of acute lymphoblastic leukemia B‐cell type with chromosomal rearrangements involving the T‐cell receptor breakpoint at band 14q11
Authors: Cigudosa J. C. , Calasanz M. J. , Gullón A. , Prósper F. , Cuesta B. , Rifón J. , Rocha E.
Published: February 2007

A patient with B‐cell acute lymphoblastic leukemia (ALL) and a translocation t(8;14) (q24;q11) is described. Translocation t(8;14)(q24;q32) is commonly associated with B‐cell leukemia; nevertheless, translocations affecting chromosome 14 at band q11 are associated with T‐cell malignancies, since the locus 14q11 contains genes that encode for the α and δ chains of the T‐cell receptor (TCR). This finding points to the idea that the association between 14q11 rearrangements and T‐cell neoplasia is less than complete. © 1992 Wiley‐Liss, Inc.
Influence of calcium permeabilization and membrane‐attached hemoglobin on erythrocyte deformability
Authors: Friederichs E. , Farley R. A. , Meiselman H. J.
Published: February 2007

The present study was designed to evaluate the influence of intracellular calcium [Ca]1 regulated membrane attached hemoglobin (Hbm) on the deformability of human RBC and ghosts. [Ca]1 of RBC was elevated via the Ionophore A23187 (10 μM); the deformability of RBC and resealed ghosts was determined via measuring RBC and ghost transit times through 5 μm diameter pores with the Cell Transit Analyzer (CTA). Salient results included: (1) significantly increased RBC levels of Hbm following ionophore treatment; (2) elevated Hbm with increasing lysing medium calcium concentration (0–5 mM); (3) decreased deformability of both intact RBC and ghosts with increasing Hbm and significant (P < 0.02 or better) linear relationships between Hbm and RBC or ghost transit times; and (4) an increased sensitivity to ionophore treatment/membrane attached hemoglobin for the higher percentiles of the CTA transit time distribution (i.e., for more rigid subpopulations). Our results thus indicate that calcium‐induced interaction of hemoglobin with the RBC membrane produces cellular rheological changes; in addition, they demonstrate the usefulness of the CTA system in measuring both average RBC rheologic behavior and the distribution of cellular rheologic properties within an erythrocyte population. © 1992 Wiley‐Liss, Inc.
Treatment of acute myeloid leukemia in the elderly with low‐dose cytarabine, hydroxyurea, and calcitriol
Authors: Slapak Christopher A. , Desforges Jane F. , Fogaren Terry , Miller Kenneth B.
Published: February 2007

Twenty‐nine patients aged 62–82 years with acute myeloid leukemia (AML) were treated with a 21‐day course of continuous infusion cytarabine, oral hydroxyurea, and 1,25‐dihydroxyvitamin D3 (calcitriol). Ten patients had an antecedent myelodysplastic syndrome. Calcitriol was continued as the only postremission therapy. Thirteen patients (45%) obtained a complete remission, and 10 patients (34%) had a partial response for an overall 79% response rate. There were three early deaths. The median remission duration was 9.8 months. Overall median survival was 12 months for all patients and 14 months for responding patients. All responding patients had marked bone marrow hypoplasia. Twenty patients received part or all of their chemotherapy as outpatients. This regimen has acceptable toxicity and can result in prolonged remissions in elderly, high‐risk patients with AML. The favorable results may be related to the synergistic effect of hydroxyurea, cytarabine, and calcitriol. © 1992 Wiley‐Liss, Inc.
Serum granulocyte colony‐stimulating factor in patients with repeated infections
Authors: Kawakami Mutsumi , Tsutsumi Hisashi , Kumakawa Toshiro , Hirai Makiko , Kurosawa Shinichiro , Mori Mayumi , Fukushima Masafumi
Published: February 2007

We have already reported significant elevation of serum granulocyte colony‐stimulating factor (G‐CSF) in the acute phase of infection. In this study, we compared the responses to infection between patients with frequently repeated infection (repeaters) and others (non‐repeaters). We examined the clinical data and serum G‐CSF levels in 48 patients with acute infections. Serum G‐CSF levels were significantly lower in repeaters than in non‐repeaters (197.7 ± 370.0 vs. 1014.1 ± 924.4 pg/ml. P < 0.001). There were no significant differences in age, serum total protein, or cholinesterase between the groups, but serum albumin was significantly lower in repeaters than in non‐repeaters (2.87 ± 0.5 vs. 3.31 ± 0.4 g/dl. P < 0.005). It is suggested that administration of recombinant G‐CSF may be useful for patients with repeated infections. © 1992 Wiley‐Liss, Inc.
Reduced erythropoietin secretion in senile anemia
Authors: Kario Kazuomi , Kodama Kazuya , Matsuo Takefumi , Nakao Kazukiyo , Asada Reiko
Published: February 2007

To investigate the etiology of the age‐related decrease in hemoglobin (Hb) concentration, we measured serum erythropoietin (EPO), serum iron, total iron binding capacity, and serum feritin levels in 247 elderly subjects aged 60–99 years. EPO levels were determined by radioimmunoassay. An age‐related increase in the serum EPO concentration (r = 0.220; P < 0.01) and a significant inverse relationship between EPO and Hb concentrations were found in normal elderly subjects without anemia (r = –0.302; P < 0.001), but not in 111 younger controls. Serum EPO levels were slightly higher in elderly subjects with preanemic iron deficiency than in the normal elderly subjects (P < 0.05). These results suggest that the EPO secretion is accelerated in the elderly even though the Hb remains above 12.0 g/dl, probably as a compensatory mechanism for peripheral tissue hypoxia. An inverse relationship between the EPO and Hb concentrations was found in the elderly subjects with iron deficiency anemia, but not in those with unexplained senile anemia. The changes of EPO levels were also assessed in 20 elderly subjects who had developed anemia when reviewed after 12 months. Serum EPO levels increased in relation to the decrease in Hb concentration in those with iron deficiency anemia, but not in those with unexplained senile anemia. Reduced EPO secretion thus seems to play a role in the progression of unexplained senile anemia, and recombinant human EPO may possibly be effective for treating this type of anemia by mobilizing excess iron. © 1992 Wiley‐Liss, Inc.
Hereditary hemolytic disease with increased red blood cell phosphatidylcholine and dehydration: One, two, or many disorders?
Authors: Clark Margaret R. , Shohet Stephen B. , Gottfried Eugene L.
Published: February 2007

We have compared characteristics of red cells from patients who were originally diagnosed as having two different disorders, high phosphatidyl choline hemolytic anemia (HPCHA) and hereditary xerocytosis (HX). Both types of cells had reduced intracellular potassium, with attendant cell dehydration and an increase in the relative amount of membrane phosphatidyl choline. Neither these observations nor a review of previous studies of HX and HPCHA revealed any means of distinguishing between the two disorders. Measurements of chloride‐dependent potassium transport revealed flux characteristics in both HX and HPCHA red cells that were different from those in simultaneously run control samples. HX and HPCHA red cells did not show the same kinds of deviations from the normal pattern. However, extensive characterization of transport behavior under a variety of controlled conditions will be required to determine whether these differences represent intrinsic differences in chloride‐dependent transport properties. It appears likely that HX and HPCHA both represent a spectrum of disorders resulting from a variety of defects that produce the same general pattern of abnormalities in cation content and membrane phospholipid composition © 1993 Wiley‐Liss, Inc.
Acute episodic hemolysis in the African black rhinoceros as an analogue of human glucose‐6‐phosphate dehydrogenase deficiency
Authors: Paglia Donald E.
Published: February 2007

Sudden episodes of massive hemolysis have become the most common cause of death among captive black rhinoceroses, and there is evidence that they occur in the wild as well. We have observed radically unique enzyme and metabolite profiles in normal rhinoceros erythrocytes compared to humans and other mammals, including marked deficiencies of intracellular adenosine triphosphate (ATP), catalase, adenosine deaminase, and other enzymes involved in glycolysis, glutathione cycling, and nucleotide metabolism. Minimal concentrations of ATP appear to impair effective acceleration of hexosemono‐phosphate shunt activity in response to oxidants by restricting substrate generation at the hexokinase step. Antioxidant defenses are further compromised by catalase deficiency, which may be a general characteristic of rhinoceros erythrocytes, perhaps related to the common occurrence of severe mucocutaneous ulcerative disease. It is proposed that erythrocyte ATP deficiency in rhinoceroses may be an evolutionary adaptation conferring selective advantage against common hemic parasites, comparable to the role of human glucose‐6‐phosphate dehydrogenase (G‐6‐PD) deficiency in falciparum malaria. © 1993 Wiley‐Liss, Inc.
Study of glucose‐6‐phosphate dehydrogenase: History and molecular biology
Authors: Beutler Ernest
Published: February 2007

Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency was discovered in the 1950s. The history of the development of knowledge about G6PD deficiency is reviewed here. In the first decade after its discovery, the clinical manifestations of G6PD deficiency began to be understood. In the second decade, attention was focused on the degree of variability of this enzyme and the distinction of the various biochemical variants from one another. In the last decade, it has been possible to understand the mutations that effect this enzyme at the DNA level. Some 40 different mutations have now been characterized. Analysis of these mutations indicates that, while diversity sometimes exists within a mutation considered biochemical homogeneous, more often variants thought to be distinct prove to be identical. The study of G6PD mutations is beginning to provide insight into structurefunction relationships. © 1993 Wiley‐Liss, Inc.
A concise review: Iron absorption—The mucin‐mobilferrin‐integrin pathway. A competitive pathway for metal absorption
Authors: Conrad Marcel E. , Umbreit Jay N.
Published: February 2007

Newly identified iron binding proteins isolated from rat duodenal homogenates permit better understanding of iron absorption. Mucins bind iron at acid pH to keep iron soluble and available for absorption at the more alkaline pH of the duodenum; this explains iron deficiency following prolonged achlorhydria. Integrin (90/150 kD) was identified on the absorptive surface of enterocytes in association with radioiron and is believed to facilitate transit of iron through the microvillous membrane. Mobilferrin, a 56 kD iron binding protein, was isolated from enterocyte cytosol. It coprecipitates with integrin and appears in close association with integrins in the apical cytoplasm. We postulate it accepts dietary iron from integrin and acts as the shuttle protein for iron in the cytoplasm. Since iron in enterocytes remains in equilibrium with body stores, we postulate mucosal iron uptake is regulated by the number of iron binding sites either occupied or unoccupied by iron on mobilferrin. Iron repletion of enterocytes from body stores is accomplished via transferrin receptors on the posterolateral membranes of enterocytes. Increased transfer of iron from blood into absorptive enterocytes occurs in iron replete animals to inhibit mucosal uptake of dietary iron. Little transfer of iron from plasma to enterocytes occurs in iron deficiency. Enhanced mucosal transfer of iron into the body occurs with increased body need for iron. The exact mechanism for mucosal transfer of iron into the plasma has not been defined but may also be mediated by an integrin. © 1993 Wiley‐Liss, Inc.
Antisense suppression of transferrin receptor gene expression in a human hepatoma cell (HuH‐7) line
Authors: Sasaki Katsunori , Zak Olga , Aisen Philip
Published: February 2007

A recombinant plasmid carrying human transferrin receptor cDNA in reverse orientation downstream from the human cytomegalovirus immediate early promoter/enhancer element was introduced into the HuH‐7 human hepatoma cell line by lipofection. Cell surface transferrin binding and iron uptake from transferrin each decreased by about 50% in stable transfectants bearing integrated antisense DNA expression vector. Northern blot analysis indicated that the abundance of target transferrin receptor message was not altered by antisense RNA. These results suggest that the antisense transcript interferes with expression of the endogenous transferrin receptor gene at the level of translation. © 1993 Wiley‐Liss, Inc.
Agranulocytosis during antibiotic therapy: Drug sensitivity or sepsis?
Authors: Pisciotta Anthony V.
Published: February 2007

Forty‐three patients reviewed from the literature and five cases of agranulocytosis during antibiotic therapy studied by the author are presented. Time required to develop agranulocytosis with antibiotics was <19 days in comparison to >40 days required with nonantibiotic drugs. In all, agranulocytosis occurred concomitantly with drug treatment and became normal as treatment was discontinued. Retrospective rechallenge studies suggest that agranulocytosis may be dose related. In all cases PMNs were almost completely deleted and marrows were devoid of granulocyte precursors. In contrast, leukopenia secondary to overwhelming sepsis displayed persisting granulocytes in peripheral blood and marrow. While leukagglutinins were not found in nine cited cases, four serums were toxic to test PMNs as measured by suppression of postphagocytosis respiratory burst. Clindamycin directly suppressed development of CFU‐G in one sensitive patient but not in 16 normal controls. The hazard of antibiotics in suppressing granulocytopoiesis is emphasized by these observations. © 1993 Wiley‐Liss, Inc.
Inhibition of the activation of hageman factor (factor XII) by eosinophils and eosinophilic constituents
Authors: Ratnoff Oscar D. , Gleich Gerald J. , Shurin Susan B. , Kazura James , Everson Barbara , Embury Paula
Published: February 2007

Several syndromes characterized by striking eosinophilia may be complicated by thrombosis. The experiments described indicate that, paradoxically, eosinophils and certain of their constituents inhibit the activation of Hageman factor (HF, factor XII). In earlier studies, suspensions of mixed types of granulocytes, other nucleated peripheral blood cells, and platelets inhibited activation of Hageman factor by ellagic acid, glass, and sulfatides. After these cells were sedimented by centrifugation, the supernatant fluids were also inhibitory. No attempt had been made earlier to distinguish among different granulocytic species. In the present study, suspensions of eosinophils and the supernatant fluid after eosinophils had been separated by centrifugation inhibited activation of Hageman factor by ellagic acid. The protein concentration of that amount of supernatant fluid that inhibited activation by about half was 16 μg/ml, approximately the same as had been described for suspensions of peripheral blood mononuclear cells. Activation of Hageman factor by ellagic acid was also inhibited by certain constituents of eosinophils, including eosinophil peroxidase, eosinophil major basic protein and eosinophil cationic protein. Inhibition was not specific for ellagic acid‐induced activation of Hageman factor, as inhibition was also observed with sulfatide‐induced activation. Inhibition was presumably related to neutralization of the negative charge of activators of Hageman factor. Thus, bismuth subgallate, a particulate activator of Hageman factor, was no longer effective after it had been exposed to eosinophil cationic protein. The observations reported here raise the question of whether in vivo eosinophils modulate certain of the defense reactions ascribed to Hageman factor. © 1993 Wiley‐Liss, Inc.
Flow cytometric analysis of the ploidy of normoblasts in the peripheral blood of patients with beta‐thalassemia
Authors: Fibach Eitan , Rachmilewitz Eliezer A.
Published: February 2007

The chronic severe anemia of patients with β‐thalassemia major stimulates extensive erythropoiesis, which results in circulating nucleated normoblasts. We devised a dual staining flow cytometric procedure in order to analyse the cell cycle and ploidy of these normoblasts. Peripheral blood cells of O blood‐group type were first stained with Fluorescein Isothiocyanate (FITC)‐conjugated anti‐H lectin which labels erythroid cells (RBC and normoblasts) by green fluorescence, and then with propidium iodide (PI) which binds to ONA and thereby labels nucleated cells (leukocytes and normoblasts) by red fluorescence. The leukocytes and normoblasts present in the blood sample of thalassemic patients could be distinguished and “gated” based on their green fluorescence. The PI (red) fluorescence, i.e., the DNA histogram of each population, was thus obtained. The results indicated no statistically significant difference in the PI fluorescence of these two populations. Thus, in spite of the abnormal erythropoiesis in β‐thalassemia, the resultant orthochromatic normoblasts are normal with respect to their DNA content © 1993 Wiley‐Liss, Inc.
Triclonal gammopathy (IgAk, IgGk, and IgMk) in a patient with plasmacytoid lymphoma derived from a monoclonal origin
Authors: Murata Takashi , Fujita Hiroyuki , Harano Hiroshi , Hukawa Masaya , Kanamori Heiwa , Matsuzaki Michio , Mohri Hiroshi , Kudoh Jun , Shimizu Nobuyoshi , Okubo Takao
Published: February 2007

We report the case of a 64‐year‐old woman with plasma cytoid lymphoma of the ileum and gastric wall. Serum protein electrophoresis and immunoelectrophoresis showed a triclonal IgGk, IgAk, and IgMk gammopathy. Biopsy of the tumor revealed three different cell types, which were stained with antibodies specific for IgG, IgA, and IgM. However, DNA analysis of immunoglobulin gene rearrangements using JH, Cμ, and Ck gene probes showed a monoclonal pattern. These results suggest that the three types of malignant cells producing different classes of immunoglobulins were derived from a single clone of B‐cells that had undergone a “class switch”. © 1993 Wiley‐Liss, Inc.
Effectiveness of cryosupernatant therapy in refractory and chronic relapsing thrombotic thrombocytopenic purpura
Authors: Obrador G. T. , Zeigler Z. R. , Shadduck R. K. , Rosenfeld C. S. , Hanrahan J. B.
Published: February 2007

This report describes objective improvement in two patients with poorly responsive thrombotic thrombocytopenic purpura (TTP) syndromes (with cryosupernatant). The first had a partial response to plasma exchange with whole plasma (fresh frozen plasma; FFP) and responded dramatically when switched to plasma exchange with cryosupernatant replacement. The second had chronic TTP (three relapses in 9 months) that required prolonged courses of exchange with FFP (∼ 1 month each) to achieve remission. Attempts to manage her recurrent TTP with infusion of two units of FFP had been unsuccessful. The latter patient was tried on cryosupernatant infusions (2 units daily) and responded within 4 days. Moreover, she has been in continuous remission for 12 months while receiving 2 units (one to three times per week). These results suggest that cryoprecipitate‐poor plasma may offer advantages over whole plasma in the management of both acute and chronic forms of TTP. © 1993 Wiley‐Liss, Inc.
Altered properties of erythrocytes in the aged
Authors: Kosower Nechama S.
Published: February 2007

Erythrocytes in the aged have a decreased life span. The properties of the red blood cells of old individuals are compared to those of the cells of young individuals. In young individuals, removal of the normal erythrocyte at the end of its lifespan is determined by a signal(s) due to (1) modified phospholipids, (2) modified carbohydrate residues, and/or (3) modified proteins. Similar changes may occur in the erythrocytes of old individuals but at a greater rate. In particular, the enhanced degradation of band 3 protein by calpain may provide a senescence signal. © 1993 Wiley‐Liss, Inc.
De novo initiation codon mutation (ATG→ACG) of the β‐globin gene causing β‐thalassemia in a swiss family
Authors: Beris P. , Darbellay R. , Speiser D. , Kirchner V. , Miescher P. A.
Published: February 2007

Investigation of microcytic anemia with normal ferrous status in two members (father and daughter) of a Swiss family originating from Bern revealed high levels of HbA2 (4%, 7.3%) and HbF (3.2%, 3.1%). Direct sequence analysis of asymmetrically amplified DNA showed the ATGǍG mutation in the initiation codon of the β‐globin gene. Heterozygous β‐thalassemia was not found in either of the propositus's parents or in any of his brothers and sisters. Extended restriction fragment length polymorphism haplotyping of the β chromosomes led us to the conclusion of a recent spontaneous mutation in the paternal germ cell. The results of routine HLA and blood group testing supported the stated paternity. We also found that the intragenic sequence polymorphisms (frameworks) are not always in linkage disequilibrium with the Bam HI polymorphism downstream from the β‐globin gene as previously observed. This is the second family found to carry this initiation codon mutation in the β‐globin gene. Unlike the first reported family, of Yugoslavian origin, our patients have high HbF levels and this in the absence of a C→T substitution at‐158 site 5′to Gγ. © 1993 Wiley‐Liss, Inc.
Induction of hypomagnesemia during amsacrine treatment
Authors: Seymour John F.
Published: February 2007

Serious cardiac arrhythmias and QT interval prolongation have been reported following Amsacrine chemotherapy. The underlying mechanism is unknown. In this study, electrolyte and electrocardiographic parameters were prospectivety studied in patients with acute myeloid leukemia (AML) treated with an Amsacrine containing combination chemotherapy regime. Data were collected immediately before and at 20 (+20) and 90 (+90) min after commencement of Amsacrine administration. Sixteen episodes were studied in six consecutive patients over a continuous 9 month period. One patient developed asymptomatic ventricular tachycardia during administration. Results from +20 and +90 min were compared with baseline by Wilcoxon matched pairs test. There was no significant change in potassium, albumin, or ionized calcium concentration at +20 or +90 min. The magnesium concentration at +20 min was significantly reduced (mean −0.04 mmol/liter; P < 0.05) but not so at +90 min. Sodium concentration at +20 min was significantly reduced (mean −1.9 mmol/liter; P < 0.01). Electrocardiographic analysis showed no significant alteration in PR interval or QRS duration. Heart rate fell significantly from baseline, mean change −10 and −8 min−1 at +20 and +90 min, respectively (P < 0.01 for both). Corrected QT interval (QTc) was significantly prolonged at +20 min (+0.05) and +90 min (+0.05) (P = 0.0001 and P < 0.0001, respectively). This study confirms the high incidence of QTc prolongation with Amsacrine administration and suggests that transient hypomagnesemia may contribute to the risk of cardiac arrhythmia in this setting. © 1993 Wiley‐Liss, Inc.
Abnormalities of von willebrand factor multimers in drug‐associated thrombotic microangiopathies
Authors: Charba Deane , Moake Joel L. , Harris Margie A. , Hester Jeane P.
Published: February 2007

Six patients with thrombotic microangiopathy associated with drug therapy had serial analyses of von Willebrand factor (vWF) multimeric patterns in their EDTA‐plasma samples by sodium dodecyl sulfate‐1% agarose gel electrophoresis and autoradiography. In the plasma of five patients (one with chronic myelogenous leukemia, two with prostatic cancer, and two with lymphoma), vWF abnormalities were observed during evolution of the thrombotic microangiopathy. These abnormalities were either the presence of unusually large (UL)vWF multimers of the type similar to those found within, and released or secreted by, endothelial cells (three patients) or a relative decrease in the largest plasma vWF multimers of the type that can be induced to attach to platelets (one patient) or both vWF abnormalities in different serial samples (one patient). In the one cardiac transplant patient who did not develop vWF multimeric abnormalities associated with thrombotic microangiopathy, vWF antigen levels were elevated more than threefold. This later individual received therapy with cyclosporin A alone. The other five thrombotic microangiopathy patients received cyclosporin A in combination with other chemotherapeutic agents (two patients); mitomycin‐C, along with other chemotherapy (two patients); or multiple chemotherapeutic drugs, but not cyclosporin A or mitomycin C (one patient). The finding of vWF multimeric abnormalities during serial analysis of plasma samples from five of six patients with drug‐associated thrombotic microangiopathy suggests the possibility that ULvWF forms derived from damaged or stimulated endothelial cells, along with the largest plasma vWF multimers, may be involved in the intravascular platelet clumping that is an essential part of the pathophysiology of this disorder. © 1993 Wiley‐Liss, Inc.
Platelet multielemental composition, lability, and subcellular localization
Authors: Gorodetsky Raphael , Mou Xiaode , Blankenfeld Avigdor , Marx Gerard
Published: February 2007

Diagnostic X‐ray spectrometry (DXS), based on X‐ray fluorescence, was used to quantitate directly the multiple elemental composition of washed, intact human platelets (n = 16), with the following results: K = 3.08 ± 1.00 mg/g, Ca = 1.18 ± 0.29 mg/g, Zn = 35 ± 9 μg/g. These values show that washed platelets contain significant pools of K, Ca, and Zn, the latter some 30–60‐fold higher than plasma levels. Dialysis of whole platelets against cation exchange resin (Chelex‐100) did not extract Ca(II) and Zn(II) sequestered within whole cells. To identify the subcellular locale of the elements, platelet lysate was subjected to 30–70% sucrose gradient ultracentrifugation and subcellular enriched fractions were obtained. Fractions were analyzed by DXS (for elements), electron microscopy (for dense granules), and subcellular markers fibrinogen and von Willebrand factor. In contrast to Ca and K, which accumulate in the dense granules and the cytoplasm, respectively, Zn appears to be distributed in the α‐granules (40%) and the cytoplasm (60%). The subcellular distribution of Zn(II) is discussed within the context of the sensitivity of platelet response to the availability of Zn(II) and the platelet release reactions following stimulation. © 1993 Wiley‐Liss, Inc.
Doppler velocimetry in pregnant patients with sickle cell anemia
Authors: Billett Henny H. , Langer Oded , Regan Owen T. , Merkatz Irwin , Anyaegbunam Akolisa
Published: February 2007

Women with sickle cell anemia have an increased risk of bearing low‐birth‐weight (LBW) progeny. To establish prognostic indicators of neonatal outcome, 15 women with sickle cell anemia were followed through their pregnancies with the use of umbilical and uterine Doppler flow velocimetry. The systolic/diastolic ratios obtained were correlated with neonatal birth weight, gestational age, and birth weight percentile. Pregravid hemoglobin levels, reticulocyte counts, dense cell numbers, percentage hemoglobin F, and indirect bilirubin and lactate dehydrogenase levels were also determined, and statistical analysis was performed to assess whether any of these parameters would be useful in conjunction with velocimetry. We report here that, in sickle cell anemia, prenatal umbilical and uterine Doppler velocimetry ratios correlate inversely and significantly with neonatal birth weight (P < 0.005 and P < 0.002, respectively). In addition, prenatal maternal HbF levels also correlate significantly with Doppler velocimetry readings, an independent indicator of LBW progeny. Neither pregravid hemoglobin levels nor dense cell concentration correlates with Doppler umbilical and uterine flow velocimetry ratios determined during pregnancy. Pregravid high levels of HbF and velocimetry readings may serve to delineate a subset of sickle cell patients who may have different requirements for prenatal care. The possible mechanism for the detrimental effects of increased levels of fetal hemoglobin has not been clearly established, but it may involve increased propensity for vasoocclusion due to the unique rheology of the human placenta. © 1993 Wiley‐Liss, Inc.
Addition of serum from patients with collagen diseases increases to cultured human endothelial cells production and release of von willebrand factor
Authors: Kagawa Hideo , Okubo Susumu , Iwata Koji , Nomura Shosaku , Yasunaga Kojiro
Published: February 2007

The addition of sera from patients with collagen diseases, particularly those with vascular complications, to the supernatant of cultured vascular endothelial cells (EC) in vitro significantly increased the surface and intracellular amounts of von Willebrand factor antigen (vWF:Ag) compared with results obtained with sera from normal healthy subjects. Peak levels of vWF:Ag occurred after 24 h of in vitro culture. Moreover, the amounts of vWF:Ag secreted into the EC supernatant with patient serum added were significantly higher than the amounts secreted into EC supernatant with control serum added, even after 48 h of in vitro culture. Levels of large and intermediate multimers (LIM) of von Willebrand factor (vWF) increased in EC supernatant exposed to serum from patients with collagen diseases as compared with levels in supernatant exposed to serum from normal controls, whereas no significant differences were detected overall between adding the plasma of patients and of normal subjects. In addition, C‐reactive protein (CRP) induced a time‐ and dose‐related release of vWF:Ag from EC, while glucocorticoid did not effect the release of vWF:Ag from EC. These results suggest that the sera of patients with collagen diseases, particularly those with vascular complications, stimulate the production and release of LIM of vWF from EC. © 1993 Wiley‐Liss, Inc.
Prevention of hypermenorrhea with leuprolide in premenopausal women undergoing bone marrow transplantation
Authors: Ghalie Richard , Porter Carlene , Radwanska Eva , Fitzsimmons William , Richman Carol , Kaizer Herbert
Published: February 2007

We report on the use of leuprolide to prevent heavy menstrual bleeding that often occurs before platelet engraftment in premenopausal women undergoing bone marrow transplantation (BMT). Leuprolide, a synthetic analog of gonadotropin‐releasing hormone (Gn‐RH‐a), was given to 34 patients by intravenous bolus injection, 1 mg daily, until platelet recovery. The median duration of therapy was 50 days (range 16–170). When necessary, patients self‐administered the drug after discharge from the hospital. No adverse effects could be related directly to the use of leuprolide. Leuprolide effectively prevented menstruation in 25 patients (73%), failed in seven (21%), and two patients were not evaluable. The success of leuprolide therapy was related to the time of onset of treatment, as anticipated from the gradual effect of Gn‐RH‐a on the menstrual cycle. The failure rate was only 6% (one of 16 patients) when leuprolide was started at least 2 weeks prior to the development of thrombocytopenia, compared to a failure rate of 33% (six of 18 patients) when leuprolide was started at a later time. We conclude that leuprolide as a single agent is a safe and effective method to prevent menstrual bleeding during BMT. Additional studies are needed to determine the best timing for the onset of therapy and the relative benefit of leuprolide compared to other prophylactic approaches in patients with lengthy thrombocytopenia. © 1993 Wiley‐Liss, Inc.
Viridans streptococcal shock in bone marrow transplantation patients
Authors: Steiner Marie , Villablanca Judith , Kersey John , Ramsay Norma , Haake Robert , Ferrieri Patricia , Weisdorf Daniel
Published: February 2007

We have recognized a rapidly progressive, often fatal shock syndrome associated with viridans streptococcal sepsis following bone marrow transplantation (BMT). Of 832 patients receiving a marrow transplant at the University of Minnesota between 1976 and 1988, including 123 with viridans streptococcal bacteremia, 10 patients (8%) developed clinical shock within an average of 2 days (range 0–4 days) of their first positive blood culture. Viridans streptococcal shock occurred in patients early in the transplantation course, between 1 and 28 (median 6) days following BMT when all 10 patients were neutropenic. Six of the 10 patients died as a consequence of their shock or from subsequent complications. The most frequent (6 of 10 patients) viridans streptococcal species isolated in the shock patients was Streptococcus mitis. Of multiple factors analyzed for increased risk of developing viridans streptococcal shock, only younger patient age was significantly associated with the development of shock. Although 58% of BMT recipients with viridans streptococcal bacteremia were younger than 15 years, all 10 patients comprising the shock population were <15 years of age (P < 0.02). We speculate that certain streptococcal strains may trigger fulminant shock in the immunocompromised BMT patient. © 1993 Wiley‐Liss, Inc.
Unstable alpha‐chain hemoglobin variants with factitious beta‐thalassemia biosynthetic ratio: Hb questembert (α131[H14] Ser→Pro) and Hb Caen (α132[H15] Val→Gly)
Authors: Wajcman H. , Vasseur C. , Blouquit Y. , Rosa J. , Labie D. , Najman A. , Reman O. , Leporrier M. , Galacteros F.
Published: February 2007

Hb Questembert [α131(H14) Ser→Pro] was found in several members of a French family suffering from congenital Heinz body anemia. The unstable hemoglobin was expressed in the peripheral red blood cells at a very low level. Globin biosynthetic studies revealed a high specific activity of the abnormal chain and an α‐/β‐labeling ratio similar to that of β‐thalassemia trait. Hb Caen [α132(H15) Val→Gly] is another unstable variant with the same globin biosynthesis abnormality. In both cases the structural modification is localized at the end of the H helix, a region encoded by the third exon. The mechanism for the unbalanced globin synthesis is not yet clear. It may be related 1) to a defect in chain assembly, 2) to an increased rate of degradation of the variant chain followed by the release of unlabeled β‐chains from the abnormal hemoglobin, thus leading to an apparent suppression of β‐chain synthesis, or 3) to a modified stability of the abnormal α‐globin mRNA. © 1993 Wiley‐Liss, Inc.
Loss of high‐responder inhibitors in patients with severe hemophilia A and human immunodeficiency virus type 1 infection: A report from the multi‐center hemophilia cohort study
Authors: Bray G. L. , Kroner B. L. , Arkin S. , Aledort L. W. , Hilgartner M. W. , Eyster M. E. , Ragni M. V. , Goedert J. J.
Published: February 2007

To evaluate the effects of human immunodeficiency virus type 1 (HIV‐1) infection on the loss of factor VIII alloantibodies, we identified 77 patients with a history of inhibitors from among a large cohort of HIV‐1‐infected participants enrolled in a natural history study of HIV‐1 infection in hemophilia. Fifty‐six patients were high responders with inhibitors titers greater than 5 Bethesda Units (BU) measured on at least one occasion. From May 1985 to December 1989, 13 of the high‐responder patients were rechallenged with factor VIII concentrates after several years of treatment with other plasma products. All exhibited excellent hemostasis upon reinstitution of factor VIII. Seven of the 13 patients (11.3–46.3 years of age) were in the advanced stages of HIV‐1 infection at the time of rechallenge. Inhibitor titers measured subsequent to the reinstitution of factor VIII were consistently less than 1 BU in five of these seven patients. The remaining six patients (6.1–57.5 years of age) had mild to moderate CD4+ lymphocyte depletion (absolute CD4+ cells: 262–935/ mm3) at the time of factor VIII rechallenge. Follow‐up inhibitor titers were negative 7–42 months after consistent factor VIII use in these six patients. The lack of anamnestic response to factor VIII in all 13 patients who were rechallenged indicates that HIV‐1‐infected patients who have a history of high‐responder inhibitors frequently benefit from the reintroduction of factor VIII use for the control of bleeding, regardless of their stage of HIV‐1 disease. © 1993 Wiley‐Liss, Inc.
Pyridoxine responsive hereditary sideroblastic erythropoiesis and iron overload: Two microcytic subpopulations in the affected male, one normocytic and one microcytic subpopulation in the obligate female carrier
Authors: Harris John W. , Danish Elizabeth H. , Brittenham Gary M. , McLaren Christine E.
Published: February 2007

Mild hepatic iron overload has been demonstrated by magnetic susceptibility measurements in a 22‐year‐old man with hereditary sideroblastic erythropoiesis despite hemoglobin levels in the normal range and a normal erythropoietin level. His grandfather's sideroblastic anemia has been found to be responsive to pyridoxine; his mother's hemoglobin has persisted in the normal range but red cell volume distribution analysis demonstrated two subpopulations; 30% with estimated geometric mean of 68 fl and 70% an estimated mean of 93 fl. Red cell distribution analysis of the grandson demonstrated two microcytic subpopulations; 46% with an estimated geometric mean of 45 fl and 54% an estimated mean of 70 fl. A therapeutic regimen is outlined to reduce to normal his iron stores and to prevent the future development of excessive iron overload. © 1993 Wiley‐Liss, Inc.
Expression of decay‐accelerating factor and CD59 in lymphocyte subsets of healthy individuals and paroxysmal nocturnal hemoglobinuria patients
Authors: Nagakura Shoichi , Nakakuma Hideki , Horikawa Kentaro , Hidaka Michihiro , Kagimoto Tadashi , Kawakita Makoto , Tomita Motowo , Takatsuki Kiyoshi
Published: February 2007

The expression of phosphatidylinositol (PI)‐anchored complement‐regulatory membrane proteins on circulating blood cells has been well clarified; however, the PI proteins on lymphocyte subsets have not been fully analyzed yet. We examined the expression of decay‐accelerating factor (DAF) and CD59 on the T lymphocytes (CD2−, CD3+, CD4−, and CD8−) and CD20+ B lymphocytes in ten healthy volunteers and 12 paroxysmal nocturnal hemoglobinuria (PNH) patients by cytofluorometry. In healthy controls, each subset of lymphocytes showed a small population of cells weakly positive and a large population of cells strongly positive for DAF and CD59, while erythrocytes showed a single population of cells positive for the PI proteins. The two‐population expression of DAF was most distinctive in CD8− T cells among the subsets. In PNH, each subset of lymphocytes showed a moderately higher population of cells weakly positive and a smaller population of cells strongly positive for the membrane proteins compared with those in the healthy controls. Moreover, in some PNH cases, a negative population for the proteins was found in all subsets. Thus the analysis of PI‐anchored proteins on lymphocyte subsets (especially CD8− T cells) was considered to be of diagnostic value in PNH patients who receive blood transfusion after hemolytic attack of affected erythrocytes. Furthermore, the two‐population expression of PI proteins in normal lymphocytes suggests that membrane PI protein would be a new subset marker of lymphocytes.
Expression of multiple β1 integrins on circulating monoclonal B cells in patients with multiple myeloma
Authors: Jensen Gitte S. , Belch Andrew R. , Mant Michael J. , Ruether Bernard A. , Yacyshyn Bruce R. , Pilarski Linda M.
Published: February 2007

We have previously reported the presence of monoclonal, tumor‐related B lineage cells in the blood of myeloma patients. The cells are continuously differentiating, and the majority are at a very late stage of B cell differentiation into plasma cells, consistent with the hypothesis that they comprise a precursor cell subset responsible for disseminating and possibly for relapse of the disease. The pattern of β1 integrin expression on monoclonal B lineage cells from blood and bone marrow of myeloma patients was evaluated using multiparameter flow cytometry in comparison to normal blood or tissue B cells and malignant B cells from B‐CLL, B lymphoma, or plasma cell leukemia. The α4 and β1 chains were found on the majority of normal B cells, usually with a higher expression of α4 compared to β1. α5 was detectable at low density on B cells from lymph node, bone marrow, and lamina propria. The α2 and α6 chains are absent on B cells localized in normal lymphoid tissues as well as on normal blood B cells and in vitro activated B cells. In myeloma, the blood B cells express α2, α5 and α6, suggesting important functional differences between these tumor‐related B cells and their normal counterparts. The plasma cells located in myeloma bone marrow express no α2, and almost no α6, although they have variable expression of α4, α5, and β1. Thus the end‐stage plasma cells appear to lack receptors that would support a propensity for invasion of basement membranes and exit to extravascular spaces. In contrast, the circulating plasmablasts in a patient with plasma cell leukemia make up a large subset of early plasma cells expressing all integrin receptors analyzed, including α2 and α6. Malignant cells from B‐CLL and B lymphoma express only the α4 and β integrins, and some B‐CLL have very low levels of α3, but no α2, α5, or α6, suggesting that they may be limited to the vascular spaces and do not extravasate, at least for the stages of disease analyzed here. Our results are therefore consistent with a working hypothesis that invasive capacity in myeloma is to be found within the abnormal monoclonal B cells in peripheral blood, which alone among B cells or plasma cells, and like plasma cell leukemia, express multiple β1 integrins, including the α2 and α6 integrin receptors, necessary for cellular translocation across the endothelial basement membranes and into extravascular spaces. This study raises the possibility that expression of, in particular, the α2 and α6 integrins may underlie the invasiveness of these diseases and offers a new perspective for future avenues of clinical intervention.
Ultrastructure of plasma cells in a patient with J chain disease
Authors: Sawamura Morio , Kurabayashi Hitoshi , Murakami Hirokazu , Sakura Tohru , Tamura Jun'Ichi , Kubota Kazuo , Naruse Takuji , Tsuchiya Jun
Published: February 2007

Ultrastructural analysis of plasma cells was performed in a 74‐year‐old female patient with J chain disease. By electron microscopy, various characteristic findings were observed: lobulated nuclei, multinuclei, single sac loop‐like structures, flocculent filament‐like substances, nuclear inclusion bodies, cytoplasmic inclusion bodies, and multilamellar bodies. Our prior studies pointed out a poor prognosis in myeloma patients with these findings.
Correction of neutrophil chemotaxis defect in patients with gaucher disease by low‐dose enzyme replacement therapy
Authors: Zimran A. , Abrahamov A. , Aker M. , Matzner Y.
Published: February 2007

We have recently described a chemotactic defect in severely afflicted Gaucher disease patients. Two of the patients were treated with low‐dose intravenous enzyme replacement (Ceredase). Marked improvement in their hematological status, organomegaly, and growth was observed. In addition, their chemotactic defect and their tendency towards infections were corrected within 1 year of treatment.
Adult‐onset cyclic neutropenia responsive to cyclosporine therapy in a patient with ankylosing spondylitis
Authors: Storek Jan , Glaspy John A. , Grody Wayne W. , Susi Ellen , Slater Evan D.
Published: February 2007

A 45‐year‐old female with a long history of HLA‐B27‐positive ankylosing spondylitis and ulcerative colitis developed cyclic neutropenia. She was hospitalized for high fever during each of three consecutive episodes of absolute neutropenia. On the third hospitalization, granulocyte‐colony‐stimulating factor (G‐CSF), 5 μg/kg/day, was given by subcutaneous injection and resulted in an increase of absolute neutrophil count from 0 to 2.2 × 109/liter and an associated decrease of platelet count and hemoglobin as well as severe bone and joint pain predominantly in the middle and lower back and purulent diarrhea. The back pain necessitated discontinuation of the drug. Oral cyclosporine therapy was begun, and although the neutrophil count continued to oscillate, both the peaks and the nadirs were higher than previously, and symptoms of neutropenia subsided. We conclude that cyclosporine can be an effective treatment for cyclic neutropenia associated with autoimmunity since G‐CSF may cause exacerbations of autoimmune disorders.
High la (HLA‐DR) and low CD11b (Mo1) expression may predict early conversion to leukemia in myelodysplastic syndromes
Authors: Mittelman Moshe , Karcher Donald S. , Kammerman Lisa A. , Lessin Lawrence S.
Published: February 2007

The FAB classification of myelodysplastic syndromes (MDS) has been useful in predicting prognosis; however, additional methods are required to detect patients at high risk for early conversion to acute nonlymphoblastic leukemia (ANLL). Using a panel of monoclonal antibodies to myelomonocytic surface antigens (MMSA) and flow cytometry, we studied bone marrow cells from 26 patients with MDS of all five FAB subtypes. The MMSA studied included la (HLA‐DR), CD11b (Mo1), CD14 (Mo2, My4), CD13 (My7), and CD33 (My9). Marrows were considered 'positive' for a given MMSA if the percentage of reactive cells exceeded the upper limit of the normal range. Twenty‐four of twenty‐six patients (92.3%) were CD13 (My7)+, suggesting that CD13 may serve as a diagnostic marker for MDS. Ten of twelve patients who developed ANLL during a median follow‐up of 44 weeks were la(HLA‐DR)+. The Kaplan‐Meier estimated median time to leukemia (TTL) was 16 weeks for la+ patients and 88 weeks for la– patients (P = 0.004). All six patients who developed ANLL before 16 weeks from diagnosis were la+, while none of the la– patients converted to ANLL before 24 weeks. Nine of thirteen patients with low CD11b (Mo1) expression (<53% reactive cells) developed ANLL, compared with only two of 11 patients with high CD11b expression (>53% reactive cells). Kaplan‐Meier estimated TTL was 29 weeks for patients with low CD11b, compared to 160 weeks for patients with high CD11b (P < 0.05). Patients who met both criteria, la+ and low CD11b, represented the poorest prognostic subgroup, with median TTL of 13 weeks compared with 88 weeks for the others (P = 0.017), la and CD11b patterns were not specific for MDS subtype, and their expression did not correlate with blast count. These data suggest that MDS patients whose bone marrow cells demonstrate high la (HLA‐DR) and low CD11b (Mo1) expression represent a poor prognostic subgroup with short TTL. These patients may be candidates for early aggressive or investigational treatment.