bluuebunny/crossref_metadata_2025 huggingface dataset:
Zinc‐induced sideroblastic anemia: Report of a case, review of the literature, and description of the hematologic syndrome
Authors: Fiske Darrell N. , McCoy Harry E. , Kitchens Craig S.
Published: February 2007

Zinc ingestion has become increasingly popular in the lay and food faddist population. Herein described by way of a case report and review of the 13 cases in the literature is the syndrome of severe anemia associated with excessive and prolonged intake of oral zinc. The syndrome is characterized by anemia, granulocytopenia, and bone marrow findings of vacuolated precursors and ringed sideroblasts. Serum analysis reveals increased zinc levels, decreased copper levels, and a decrease in ceruloplasmin. The mechanism appears to be zinc‐induced copper deficiency, which is instrumental in producing the profound bone marrow abnormalities, as zinc itself is of low toxicity. Importantly, the syndrome is totally reversible with cessation of zinc intake. Hematologists should be aware of this form of reversible sideroblastic anemia. © 1994 Wiley‐Liss, Inc.
Detection of common deletional α‐thalassemia‐2 determinants by PCR
Authors: Baysal E. , Huisman T. H. J.
Published: February 2007

We have developed a rapid approach to detect the two most common α‐thalassemia‐2 (α‐thal‐2) determinants by the polymerase chain reaction (PCR) technique, which takes a few hours to complete. Specific oligonucleotides selectively amplify appropriate segments of the chromosome with the deletion and the normal chromosome under identical experimental conditions, and the products are identified by electrophoresis on 1.5% agarose. Characterization of the two most prevalent types of the −α3.7 determinant [–α3.7(1) and −α3.7(11)] can be made by Apa I digestion of the PCR product. Two types of α‐thal‐2 determinants, −α3.7 and −α4.2, were tested in numerous samples from various parts of the world. This approach is believed to provide a cost‐effective way to screen large numbers of blood samples in a relatively short time and can be used to identify α‐thal‐2 heterozygotes and homozygotes and compound heterozygotes (–α3.7/–α4.2) in populations where such α‐gene defects are shown to exist at high frequencies. © 1994 Wiley‐Liss, Inc.
Familial myeloproliferative syndrome
Authors: Pérez‐Encinas M. , Bello J. L. , Pérez‐Crespo S. , De Miguel R. , Tome S.
Published: February 2007

Familial chronic myeloproliferative syndrome (CMS) was observed in five members from two different generations of the same kindred. Diagnoses included agnogenic myeloid metaplasia (case 1), polycythemia vera (case 2), and essential thrombocythemia (cases 3–5). Cases 1–3 were siblings, case 5 was the daughter of case 1, and case 4 was the cousin of cases 1, 3. Age at diagnosis ranged from 28 to 75 years, cases 1 and 3 were male, and the others were female. The diagnosis was made after an episode of cerebral thrombosis in one patient, during a study for headache and dizziness in another, and fortuituously in the three remainders. All patients had splenomegaly and varying degrees of thrombocytosis. The cytogenetic exam was normal in all four cases. A woman patient was treated with interferon during a pregnancy. Fetal growth was retarded, and the newborn showed bone and genital malformations. No environmental leukemogen factor was found. This familial case strengthens Dameshek's theory of a common pathogenesis of CMS and suggests a genetic and hereditary etiology. © 1994 Wiley‐Liss, Inc.
Relationship of burst‐forming‐unit‐erythroid progenitors and their DNA‐synthesis stage to fetal hemoglobin levels in hydroxyurea‐treated patients with sickle cell anemia
Authors: Mankad Vipul N. , Baliga Surendra , Phillips Karen , Shah Arvind K. , Yang Yih‐Ming
Published: February 2007

DNA‐synthesis stage and total number of circulating burst‐forming‐units‐erythroid (BFU‐E) have been inversely correlated with hemoglobin F levels in the peripheral blood, as well as in the cells from the BFU‐E‐derived colonies obtained from homozygous sickle cell anemia (SS) patients during steady state. Similar studies in SS patients treated with cytotoxic agents have not been reported. However, regeneration of the erythroid marrow that follows the cytoreduction phase of chemotherapy has been suggested as one of the mechanisms of stimulation of fetal hemoglobin synthesis. Therefore, a longitudinal study of hemopoiesis in hydroxyurea‐treated SS patients was conducted. Thirty‐two sets of hemopoietic studies, including total circulating BFU‐E and S‐phase BFU‐E, were obtained from three patients treated with hydroxyurea. A dose‐dependent decrease in total BFU‐E colonies occurred in peripheral blood of all three patients (r = −0.58, −0.85, and −0.97, respectively, with each P < 0.05). There was a strong positive correlation between hydroxyurea dose and fetal hemoglobin levels in two of the three patients who responded clinically (r = 0.89618 and 0.88632, respectively, with each P < 0.01). When data from all patients were combined (n = 32), there was a strong, inverse, linear relationship between total number of BFU‐E and percentage S‐phase BFU‐E with fetal hemoglobin levels (r = −0.6649 and −0.7404, respectively, with each P < 0.0001). A stronger, curvilinear, multiple relationship was detected between total BFU‐E and percentage S‐phase BFU‐E with fetal hemoglobin levels (R = 0.8351 and 0.8602 with each P < 0.0001). © 1994 Wiley‐Liss, Inc.
Bepridil as an antisickling agent: Membrane internalization and cell rigidity
Authors: Johnson Robert M. , Acquaye Clemenceau , Féo Claude , Sarnaik Sharada
Published: February 2007

The calcium channel antagonist, bepridil, β‐(2‐methylpropoxy)methyl‐N‐phenyl‐N‐(phenylemethyl)‐1‐pyrrolidineethanamine monocholoride monohydrate, inhibits the sickling of deoxygenated sickle (SS) erythrocytes, as determined by light microscopy. The antisickling effect was seen only in dilute suspensions of red cells. In concentrated erythrocyte suspensions, sickling was not inhibited and measurements of hematocrit and cell density were unchanged by bepridil. The determination of cell volume in dilute suspensions was complicated by bepridil's tendency to aggregate, but rapid measurements by electronic sizing also indicated no increase in cell volume, up to a bepridil concentration of 200 μM. Ektacytometry of dilute sickle cell suspensions suggested an explanation for the anti‐sickling action of bepridil. Osmotic scan ektacytometry disclosed that bepridil initially increased the surface area of the red cell, as shown by a shift in the low osmolality minimum. This change was complete in 10 sec, the shortest time that could be measured. Subsequently, at concentrations that were observed to inhibit the sickling of deoxygenated sickle cells (100 μM or greater), red cells underwent a loss in surface area that was complete in 1 min. There was a concomitant loss of cell deformability. Light and scanning electron microscopy has previously shown that bepridil is a stomatocytic agent. Using transmission electron microscopy, we verified that the loss of surface area was a consequence of endocytosis, presumably as the end stage of the stomatocytic transformation induced by bepridil. Bepridil did not inhibit intracellular hemoglobin S polymerization even at 200 μM, as shown by oxygen scan ektacytometry. Bepridil thus appears to inhibit the sickling of deoxygenated SS cells by inducing endocytosis and lowering cell deformability. This mechanism may explain the anti‐sickling effect of other basic amphiphiles, such as chlorpromazine. © 1994 Wiley‐Liss, Inc.
Outcome of portal‐systemic shunt surgery for portal hypertension associated with intrahepatic obstruction in patients with agnogenic myeloid metaplasia
Authors: Tefferi Ayalew , Barrett Scott M. , Silverstein Murray N. , Nagorney David M.
Published: February 2007

Life‐threatening portal hypertension (PHN) in patients with chronic myeloproliferative disorders may result from increased portal flow caused by marked splenomegaly or an increased resistance to portal flow from either a large vein thrombosis or an intrahepatic obstruction usually associated with agnogenic myeloid metaplasia (AMM). The former cause is correctable by splenectomy alone, whereas the latter requires portal‐systemic shunt surgery. Few data exist regarding the outcome of portal‐systemic shunt surgery in patients with AMM and intrahepatic obstruction. During the past 25 years, 13 patients with chronic myeloproliferative disorders underwent portal‐systemic shunt surgery at our institution. The cause of PHN was intrahepatic obstruction in ten patients and hepatic vein thrombosis in three. Ten of the thirteen patients had AMM as initial diagnosis. Only one patient had intraoperative complications, and four patients had either sepsis or thrombosis during the postoperative period. Twelve patients survived the postoperative period and had a median postsurgical survival of 3 years (range, 0.25 to 19 years). The long‐term complications of the operation were very few and included hepatic encephalopathy (one patient), portal vein thrombosis (one patient), and shunt occlusion (one patient). The procedure was successful in alleviating complications of PHN in all but one patient. Deterioration of hepatic function and subsequent hepatomegaly were unusual. Portal‐systemic shunt surgery seems to be a useful option in patients with AMM and lifethreatening PHN from intrahepatic obstruction. © 1994 Wiley‐Liss, Inc.
β‐thalassemia alleles and unstable hemoglobin types among russian pediatric patients
Authors: A.çürük M. , Molchanova T. P. , Postnikov Yu. V. , Pobedimskaya D. D. , Liang R. , Baysal E. , Kolodey S. , Smetanina N. S. , Tokarev Yu. N. , Rumyantsev A. G. , Huisman T. H. J.
Published: February 2007

A recently initiated collaboration between Russian and American institutions has resulted in the characterization of several known or new β‐thalassemia alleles and unstable hemoglobin types. Nine known β‐thalassemia alleles were present which have also been found in Mediterranean, East Asian, and Black populations; the possibility of independent mutations for some of the rare alleles should be considered. Hb Durham‐N.C./Brescia with a codon 114 (CTG → CCG; Leu → Pro) change was present in six members of two families. This condition and two new variants have the characteristics of a dominant type of β‐thalassemia heterozygosity with moderate anemia, Heinz body formation, splenomegaly, etc. One new β‐thalassemia allele is a frame‐shift at codon 124 (‐A), while another is characterized by the introduction of an extra proline residue (codon: CCA) between residues Thr (β123) and Val (β126) to give the sequence ‐Thr‐Pro‐Pro‐Pro‐Val‐. © 1994 Wiley‐Liss, Inc.
Congenital afibrinogenemia
Authors: Al‐Mondhiry Hamid , Ehmann W. Christopher
Published: February 2007

Congenital afibrinogenemia is a rare disorder with unusual clinical manifestations. The disease is inherited as an autosomal recessive trait and consanguinity is common among affected families. Clinical manifestations range from minimal bleeding to catastrophic hemorrhage. Congenitally afibrinogenemic patients seem to be peculiarly susceptible to spontaneous rupture of the spleen. Coagulation tests which depend on clot formation as an end point may be infinitely prolonged and abnormalities of platelet function are usually present. The diagnosis is established by demonstrating trace or no immunoreactive fibrinogen. The disease is caused by markedly reduced or absent synthesis of fibrinogen by liver cells, but the genetic defect remains unknown. Bleeding episodes can be effectively treated with cryoprecipitate. Purified virally inactivated fibrinogen concentrates have been used in Europe and may soon be widely available. © 1994 Wiley‐Liss, Inc.
Regulation of erythropoietin production in a case of congenital erythropoietin‐dependent pure erythrocytosis
Authors: Borgna‐Pignatti Caterina , Liberato Nicola Lucio , Marradi Pierluigi , Rosti Vittorio , Barosi Giovanni
Published: February 2007

In a patient with congenital erythopoietin‐dependent pure erythrocytosis (EDPE) associated with hypersensitivity of erythroid progenitor cells to erythropoietin (Epo), the investigations planned to elucidate the mechanism responsible for hormone hyperproduction revealed that Epo synthesis was (1) independent of normal oxygen‐mediated feedback induced by phlebotomy; (2) not modulated by adenosine as a second messenger (the treatment with the adenosine antagonist theophylline in fact left unchanged the serum Epo levels); and (3) uninfluenced by iron therapy. The Epo dose—response curve for growth of erythroid progenitor was similar to that of three age‐matched thalassemia patients with increased serum Epo levels, (sEpo) suggesting that the observed erythroid progenitors hypersensitivity to Epo could represent an ex vivo artifact induced by the increased sEpo levels. © 1994 Wiley‐Liss, Inc.
Hemolytic anemia and acute renal failure associated with temafloxacin‐dependent antibodies
Authors: Maguire Robert B. , Stroncek David F. , Gale Eric , Yearlsey Martha
Published: February 2007

Quinine‐ingestion has been associated with immune‐mediated recurrent pancytopenia, hemolysis, and renal failure. The structure of fluoroquinolone antibiotics is similar to the structure of quinine. Over a 3 month period, three patients at our institution developed hemolysis and renal failure following ingestion of the fluoroquinolone antibiotic temafloxacin. Two of the three patients required hemodialysis. Following withdrawal from the drug, the hemolysis resolved and the renal function eventually returned to normal in all three patients. One patient also had a transient mild thrombocytopenia. Sera from all three patients were tested for drug‐dependent antibodies to red blood cells, platelets, and neutrophils. Temafloxacin‐dependent red cell antibodies were detected in one patient, and temafloxacin‐dependent red cell and neutrophil antibodies were detected in a second patient. No temafloxacin‐dependent antibodies were detected in the third patient. Sera from all three patients were also tested for quinine and quinidine‐dependent antibodies to red cells, platelets, and neutrophils. Sera from the patient without temafloxacin‐dependent red cell antibodies reacted with red cells in the presence of quinine. These results suggest that, at least in some patients, the toxicities associated with temafloxacin are immune mediated. © 1994 Wiley‐Liss, Inc.
Thrombomodulin: A marker for endothelial damage during orthotopic liver transplantation
Authors: Himmelreich G. , Riewald M. , Rosch R. , Blumhard G. , Neuhaus P. , Roissant R. , Riess H.
Published: February 2007

Thrombomodulin is a surface protein of vascular endothelial cells. A smaller form of thrombomodulln in blood and urine, the soluble (s) thrombomodulln, appears to be derived from injured endothelial cells or to be proteolytically cleaved from thrombomodulin by proteases. Several in vitro and in vivo studies have suggested s thrombomodulin as a marker of endothelial damage. In orthotopic liver transplantation, platelet and leukocyte activation as well as prothrombin activation are suspected of being caused by damaged endothelial cells in the graft liver. We determined s thrombomodulin antigen as well as thrombin‐antithrombin III complexes, protein C, and antithrombin III activities in the course of 23 orthotopic liver transplantations. Samples were taken at 7 different time‐points intraoperatively, as well as out of the perfusate released from the graft liver vein during the flushing procedure with arterial blood prior to the opening of the hepatocaval anastomosis. Levels of s thrombomodulin antigen and thrombin‐antithrombin III complexes showed a significant increase with reperfusion of the graft liver and levels in the perfusate were higher (both: P = 0.0001) than the corresponding systemic levels. In parallel, antithrombin III decreased significantly with reperfusion and perfusate levels of antithrombin III and protein C activities were lower in the systemic circulation (both: P − 0.0001). In conclusion, high levels of s thrombomodulin antigen in the early reperfusion phase and in the perfusate strongly indicate endothelial damage to the graft liver vascular bed, paralleled and followed by signs of prothrombin activation. © 1994 Wiley‐Liss, Inc.
The use and limitations of the INR system
Authors: Ts'ao C. , Neofotistos Demetra
Published: February 2007

This study was undertaken to answer some practical questions physicians and medical directors of clinical laboratories face when they contemplate replacing their high international sensitivity index (ISI) thromboplastins with low ISI ones and using international normalized ratio (INR) in place of prothrombin time ratio (PTR) for monitoring warfarin therapy. To the question of whether low‐ISI thromboplastins would produce a prolonged PT on normal patients, the answer is probably no. To the question of the extent of normalization of disparate PTs, determined by high and low ISI thromboplastins, of patients on oral anticoagulants upon the conversion of PTR to INR, the answer is a mixed one. For those whose PTs were 14–20 sec, conversion of PTR to INR would markedly, but not completely, normalize the PTR values. In other words, there would be a lessening of disparity of the PTR after the conversion. For patients whose PTs were >20 sec, conversion of PTR to INR could even widen the disparity seen with the PTR. Finally, when PTs were assayed on different coagulation devices with the same reagent, highly congenial results were obtained. © 1994 Wiley‐Liss, Inc.
Anti‐annexin V antibody in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody
Authors: Matsuda Juzo , Saitoh Noriko , Gohchi Kengo , Gotoh Moritaka , Tsukamoto And Miyo
Published: February 2007

We investigated anti‐annexin V antibody (aANX) in patients with systemic lupus erythe‐matosus (SLE), and correlated to positivity with lupus anticoagulant (LA)/anticardiolipin antibody (aCL). aANX was positive in 12/47 SLE patients (26%), including 7 with β2‐glycoprotein 1 (GPl)‐dependent aANX. The positivity of aANX was higher in patients with aCL (19%) and LA/aCL (50%) than in those without LA/aCL (10%). From these results, it is concluded that aANX is an autoantibody closely related to LA/aCL, and can be a possible new risk marker for thrombosis. © 1994 Wiley‐Liss, Inc.
Trends in the incidence of polycythemia vera among olmsted county, Minnesota residents, 1935–1989
Authors: Anía Basilio J. , Suman Vera J. , Sobell Janet L. , Codd Mary B. , Silverstein Murray N. , Melton L. Joseph
Published: February 2007

To investigate the suggestion that the incidence of polycythemia vera has increased in recent decades, we ascertained secular trends in the incidence of polycythemia vera in Olmsted County, Minnesota, over the 55‐year period, 1935–1989. The inpatient and outpatient medical records of all potential cases of polycythemia vera in Olmsted County residents were reviewed and the diagnostic criteria of the Polycythemia Vera Study Group were applied. We found no indication of an increase in the age‐ and sex‐adjusted incidence of polycythemia vera, which averaged 1.9 per 100,000 person‐years (95% C.I., 1.4–2.5) over the study period. Incidence rates increased with age, and age‐adjusted incidence rates were greater for men (2.8 per 100,000 person‐years; 95% C.I., 1.8–3.9) than for women (1.3 per 100,000 person‐years; 95% C.I., 0.7–1.9), with the highest incidence rate (23.5 per 100,000 person‐years) among men aged 70–79 years. Survival was reduced in this inception cohort of 50 cases, compared to that expected for individuals of like age and sex (P < 0.0001); median survival following diagnosis was 7.2 years. © 1994 Wiley‐Liss, Inc.
Inhibition of hemoglobin S polymerization by N‐terminal band 3 peptides: New class of inhibitors: Solubility studies
Authors: Danish Elizabeth H. , Lundgren David W. , Harris John W.
Published: February 2007

Two synthetic peptides corresponding to the N‐terminal amino acids (AA) of band 3 were designed to inhibit deoxyhemoglobin S (deoxy S) polymerization through two different mechanisms. Peptide I, an N:1–15AA fragment, was employed to bind to the 2,3‐diphosphoglycerate (2,3‐DPG) receptor locus of single deoxy S molecules with 5–7 AA extending internally and the remaining 10‐8 AA projecting external to hemoglobin (Hb) S, thereby inhibiting polymerization by steric hindrance. Peptide II consisted of two N:1‐8AA + K (lysine) sequences linked by a coupler through the lysine, and it was employed to bind to the 2,3‐DPG loci of two deoxy S molecules, tethering them together to form “binary hemoglobin complexes” incapable of entering the polymer chains. Decreased polymerization would result from reduction in effective concentration of deoxy S.

Binding of peptides to the 2,3‐DPG receptor loci was demonstrated by a progressive rightward shift in the hemoglobin oxygen binding curves as a function of increasing peptide concentrations.

Inhibition of deoxy S polymerization was studied by equilibrium solubility measurements of purified, stripped solutions of Hb S. Physiologically significant inhibition was demonstrated for both peptides with near‐maximum increases in solubility achieved by Peptide II at 1:1 peptide:Hb S ratios.

These peptides represent a new class of inhibitors of deoxy S polymerization. © 1994 Wiley‐Liss, Inc.
Acute spontaneous tumor lysis syndrome
Authors: Jasek Andrzej M. , Day H. James
Published: February 2007

An 83‐year‐old woman with no previous history of malignancy was admitted to our institution with weakness and anemia and subsequently developed acute tumor lysis syndrome secondary to newly diagnosed Burkitt's leukemia/lymphoma. This syndrome has been previously described in patients with hematologic malignancies; however, its development has been related to the administration of chemotherapy, steroids, or radiotherapy. The spontaneous occurrence of tumor lysis syndrome has not been previously reported; however, Cohen et al. [Am J Med 58:486–491, 1980] report 8 of 37 patients with “clinically insignificant pretreatment derangements” of serum potassium, phosphate, and calcium. © 1994 Wiley‐Liss, Inc.
Hereditary hemochromatosis: A prevalent disorder of iron metabolism with an elusive etiology
Authors: Conrad Marcel E. , Umbreit Jay N. , Moore Elizabeth G. , Parmley Richard T.
Published: February 2007

Hereditary hemochromatosis is a prevalent inherited disorder with an estimated frequency of homozygosity of 0.2 to 0.45% in Caucasians. The disease is characterized by progressive iron overload until a massive accumulation of body iron occurs. Undetected, the disorder eventually can produce either cirrhosis, diabetes mellitus, cardiac disease, arthritis, or hepatocellular carcinoma or a combination of these manifestations. Early diagnosis and treatment prevents organ damage and normalizes life expectancy. Screening studies to detect hemochromatosis are most effectively accomplished by measurement of the serum iron and total iron binding capacity. Treatment is most effectively performed by frequent phlebotomy until body stores are empty and then 3 to 4 times yearly for life. The basic defect of hemochromatosis appears to increase iron absorption, decrease iron excretion, and produce preferential deposit of iron in hepatic parenchymal cells rather than Kupffer cells. The genetic abnormality of hemochromatosis is located on chromosome 6 in close association with the gene for HLA antigens. Recent speculation postulates that tumor necrosis factor may be involved in the etiology of this disease because of its location on chromosome 6 and its effect upon iron transport. © 1994 Wiley‐Liss, Inc.
Bone marrow necrosis
Authors: Ranaghan L. , Morris T. C. M. , Desai Z. R. , Markey G. M.
Published: February 2007

Bone marrow necrosis is most frequently diagnosed at postmortem examination. Antemortem diagnosis is still uncommon. In a recent review of world literature, we have found 133 cases of bone marrow necrosis diagnosed during life. It has been observed during the course of a wide variety of diseases, most commonly in association with acute and chronic leukemia, carcinoma, malignant lymphoma, infections, and sickle cell disease.

We report two intravitally diagnosed cases of bone marrow necrosis occurring in two patients with high‐grade B‐cell lymphoproliferative disease. These cases are unusual in that both patients had a triad of bone marrow necrosis, high‐grade B‐cell lymphoproliferative disease, and hypercalcemia. Despite chemotherapy, both cases ultimately proved fatal, with progressive involvement of the central nervous system. © 1994 Wiley‐Liss, Inc.
African‐American factor VII‐deficient variants in Georgia (FVII variants)
Authors: Krauss Jonathan S. , Matthews Anthony , Oliver Joyce , Lightsey Alton , Jonah Mary H. , Pantazis Cary G.
Published: February 2007

We studied African‐American Factor (FVII)‐deficient variants and carriers in Georgia by measuring their levels of FVII antigen (FVIIAG) and FVII procoagulant (FVIIC). Factor VIIAG was determined using enzyme‐linked immunoassay (ELISA), whereas FVIIC was measured in two ways: 1) by fibrin clotting methods that employed human recombinant (HRFVIIC), human placental (HPFVIIC), rabbit brain (RBFVIIC), and bovine brain (BBFVIIC) thromboplastins; and 2) by an amidolytic method (AMFVIIC). Prothrombin time tests (PT) were also performed by standard methods. These 4 FVII‐deficient patients and 3 carriers demonstrated the following results: PT: 18.2 ± 6.5 sec; FVIIAG: 73.0 ± 14.9; HRFVIIC: 30.6 ± 20.3%; HPFVIIC: 30.5 ± 21.4%; RBFVIIC: 25.3 ± 21.4%; BBFVIIC: 30.6 ± 17.5%; AMFVIIC: 44.1 ± 18.3. We conclude that a group of clinically mild African‐American FVII‐deficient variants exists in Georgia. This group is characterized by the presence of FVIIAG and decreased FVIIC, using a variety of thromboplastins; an excellent correlation was noted for both human thromboplastins. © 1994 Wiley‐Liss, Inc.
High expression of CD56 (N‐CAM) in a patient with cutaneous CD4‐positive lymphoma
Authors: Adachi Masaaki , Maeda Kazuo , Takekawa Mutsuhiro , Hinoda Yuji , Imai Kohzoh , Sugiyama Sadao , Yachi Akira
Published: February 2007

Cutaneous lymphoma is a disease characterized with massive skin infiltration of lymphoid malignant cells. They commonly express some T‐cell markers, such as CD2, CD3, CD4, and CD7, and thus termed as CTCL (cutaneous T cell lymphoma). Here, we present a case with CD56/N‐CAM‐positive cutaneous lymphoma, which appears lymphocytic morphology and expresses CD4, but does not express CD2, CD3, CD8, CD14, CD16, CD57, and CD20. The most malignant cells contained no distinctive azurophilic granules in the cytoplasm. Southern blot analysis revealed that T cell receptor‐β, γ, and immunoglobulin heavy chain genes in the cells were in germ‐line configurations. Electron microscopic examination showed characteristics of lymphoid cells with higher nucleocytoplasmic ratio and lacked structures typical of other cell types (i.e., epithelial cells, neuroendocrine cells, and mesenchymal cells). Thus, the cells are likely to be immature lymphoid cells. Histological analysis revealed the cells infiltrate mainly into the dermis with angiocentric growth pattern. The clinical course was aggressive, with rapid involvement of bone marrow and central nervous system. These striking features of the patient may represent a novel fraction (CD2−, CD4+, and CD56+) of cutaneous lymphoma. © 1994 Wiley‐Liss, Inc.
Erythrocyte membrane vesicles and irreversibly sickled cells bind protein S
Authors: Lane Peter A. , O'Connell Jacquie L , Marlar Richard A.
Published: February 2007

Plasma levels of free protein S, a vitamin K‐dependent anticoagulant, are decreased in persons with sickle cell anemia, but the etiology of the low levels is unknown. Protein S binds to phosphatidylserine‐containing phospholipids in a calcium‐dependent manner. Other studies have indicated that phosphatidylserine may be abnormally present on the outer surface of the membrane lipid bilayer of sickle cells and of the spectrin‐depleted vesicles they shed in vivo. We studied the binding of purified, radiolabeled protein S to spectrin‐depleted erythrocyte membrane vesicles and to density‐separated fractions of sickle and normal erythrocytes. Calcium‐dependent binding of protein S occurred with vesicles and with well‐aerated dense irreversibly sickled cells, but not with well‐aerated sickle discocytes or with normal erythrocytes. These data provide further evidence that phosphatidylserine is abnormally present on the outer surface of spectrin‐depleted vesicles and of irreversibly sickled cells. In addition, protein S binding to such sickle membranes in vivo may be responsible, in part, for the decreased levels of free protein S in sickle cell plasma. © 1994 Wiley‐Liss, Inc.
A functional factor X deficiency
Authors: Sun Paul , Hata Jane , Bauer John , Haibach Carolyn , Campbell Doug , Farhangi Medhi , Smith Dan
Published: February 2007

A functional factor X deficiency is described which caused pronounced reduction in the in vitro activation of the extrinsic system while marginally affecting the in vitro activation of the intrinsic pathway. All studies were normal with the exception of a prolonged PT, an elevated factor X antigen, and low factor X activity. Western blot analysis revealed the presence of two factor X species. The abnormal molecule was of higher molecular weight. Interestingly, there was no bleeding associated with this deficiency. The biochemical basis of this defect is currently under investigation. ©1995 Wiley‐Liss, Inc.
Genetic heterogeneity of β‐thalassemia in southeast sicily
Authors: Schilirò G. , di Gregorio F. , Samperi P. , Mirabile E. , Liang R. , Cürük M. A. , Ye Z. , Huisman T. H. J.
Published: February 2007

In this study we have defined the spectrum of the β‐thalassemia mutations, the β‐thalassemia haplotypes, and the genotype‐to‐phenotype correlations in a large number of patients with different β‐thalassemia conditions. Seventeen different (β‐thalassemia mutations were detected which included one chromosome each with Hb Dhonburi and Hb Lepore. Five alleles, namely, codon 39 (C→T), IVS‐l‐110 (G→A), IVS‐l‐6 (T C), IVS‐ll‐745 (C→G), and IVS‐l‐1 (G→A), account for 90% of all β‐thalassemia mutations in 846 thalassemic chromosomes studied.

Haplotyping for a large number of subjects showed that the five common mutations are linked to a few haplotypes. The presence of milder mutations, mainly IVS‐l‐6 (T C), in about 19% of our patients explains some of the clinical variables. Among the 37 patients with thalassemia of intermediate severity, only 6 were homozygous or compound heterozygous for two severe alleles. The type of β‐thalassemia is the main factor responsible for differences in the phenotypic expression of the disease in patients with Hb S‐β‐thalassemia; patients with Hb S‐β+‐thalassemia are less severely affected than those with Hb S‐β°‐thalassemia. The five most frequent mutations have comparable distributions all Over Sicily. ©1995 Wiley‐Liss, Inc.
Combination Therapy With Recombinant Human Granulocyte Colony‐Stimulating Factor and Erythropoietin in Aplastic Anemia
Authors: Imamura Masahiro , Kobayashi Masanobu , Kobayashi Sumiko , Yoshida Kohki , Mikuni Chikara , Ishikawa Yorikazu , Matsumoto Shuzo , Sakamaki Sumio , Niitsu Yoshiro , Hinoda Yuji , Yachi Akira , Kudoh Tohru , Chiba Shunzo , Kasai Masaharu , Oka Toshiaki , Okuno Akimasa , Maekawa Isao , Sakurada Keisuke , Miyazaki Tamotsu
Published: February 2007

Recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) and erythropoietin (rhEPO) were used to treat patients with aplastic anemia (AA). In terms of effects on erythrocyte recovery, the combined use of rhG‐CSF and rhEPO showed a favorable response in 6 of 14 (42.9%) patients with moderate AA following 10 weeks treatment and in 3 of 14 (21.4%) patients thereafter. However, the response was poor in patients with severe AA (3/13). A favorable response in severe AA was observed in 1 of 13 (7.7%) patients following 10 weeks treatment and in 2 of 13 (15.4%) patients thereafter. The overall effect on erythrocytes was observed in 44.4% patients. A dose of 400 μ/m2 G‐CSF was sufficient to cause an increase in neutrophil count and 100 IU/kg rhEPO appeared to be sufficient to cause an increase in erythrocyte count. In 6 of 27 (22.2%) patients, a trilineage response was observed. Interestingly, a delayed and long‐lasting effect was obtained in 5 of 27 (18.5%) patients. These results suggest that rhG‐CSF can synergize with rhEPO in erythrocyte response, especially in patients with moderate AA.
Hyperaggregation of platelets in intestinal tuberculosis: Role of platelets in chronic inflammation
Authors: Sarode Ravindra , Bhasin Deepak , Marwaha Neelam , Roy Pallab , Singh Kartar , Panigrahi D. , Garewal Gurjeevan , Mehta S. K.
Published: February 2007

Eighty‐eight percent (38/43) patients of intestinal tuberculosis showed significant hyperaggregation of platelets (P < 0.001). Serum and plasma from 15 patients when incubated with normal platelets caused hyperaggregation. Gel filtered platelets from 2 patients suspended in normal plasma showed hyperaggregation of platelets with arachidonic acid. Tubercular protein had no effect on platelet aggregation. A role of hyperactive platelets in chronic inflammatory response is discussed. ©1995 Wiley‐Liss, Inc.
Simultaneous assessment of cell kinetics and programmed cell death in bone marrow biopsies of myelodysplastics reveals extensive apoptosis as the probable basis for ineffective hematopoiesis
Authors: Raza Azra , Mundle Suneel , Iftikhar Amna , Gregory Stephanie , Marcus Bridget , Khan Zaineb , Alvi Sairah , Shetty Vilasini , Dameron Sherry , Wright Vonda , Adler Solomon , Loew Jerome M. , Shott Susan , Ali Syed Nadir , Preisler Harvey
Published: February 2007

Despite hypercellular bone marrows (BM), peripheral cytopenias are the rule in patients with myelodysplastic syndromes (MDS). This study examined the roles played by cell birth and cell death rates in generating this paradox. Cell kinetics from BM biopsies of 35 MDS patients were measured using intravenous infusions of either iododeoxyuridine or bromodeoxyuridine, or both. Degree of apoptosis or programmed cell death (PCD) was estimated using in situ end‐labeling of DNA directly from BM biopsies, which were simultaneously double‐labeled for proliferation/PCD. MDS were found to be highly proliferative disorders with large numbers of myeloid, erythroid, and megakaryocytic cells synthesizing DNA. Median cycling time (Tc) of myeloblasts was more rapid than that of patients with acute myeloid leukemia (44.1 hr vs. 56.0 hr). Interestingly, most marrow cells of all three lineages in 32 of 34 evaluable cases were undergoing PCD. In 19 of 32 patients, greater than 75% cells were apoptotic. Surprisingly, large numbers of S‐phase cells were found to be simultaneously undergoing PCD, as were stromal cells of the BM microenvironment. We conclude that the extensive apoptosis in hematopoietic cells effectively cancels the high birth rate resulting in ineffective hematopoiesis and accounting for deficient bone marrow function. ©1995 Wiley‐Liss, Inc.
Abnormal platelet von willebrand factor (vWF) as a marker of abnormal function in megakaryocytic dysplasia
Authors: de Cataldo F. , Baudo F. , Redaelli R. , Corno A. R.
Published: February 2007

The myelodysplastic syndromes (MDS) are neoplastic disorders of the hemopoietic system; multilineage involvement is also evidenced by specific cellular dysfunctions. The von Willebrand factor (vWF), synthesized and processed in the megakaryocytes (MK), is stored in the α granules of the platelets. The platelet vWF multimeric pattern was studied in 18 patients with MDS, and in 4 with pernicious anemia (PA), to investigate whether the processing of vWF is abnormal in the megakaryocytic dysplasia. An abnormal multimeric pattern was observed in 10/18 MDS and 4/4 PA patients. The abnormality of this specific protein is the discrete expression of the basic disorder, and is reversible when hemopoiesis is normalized. Although the data do not allow any conclusion, abnormal synthesis is the likely explanation of the abnormality. ©1995 Wiley‐Liss, Inc.
Lupus anticoagulant in children with thrombosis
Authors: Manco‐Johnson Marilyn J. , Nuss Rachelle
Published: February 2007

Nineteen children who presented with thromboses over a 7‐year period were found to have a lupus anticoagulant (LA). The initial thrombosis was proximal deep vein thrombosis (DVT) in six children, central nervous system (CNS) in five, primary pulmonary in four, distal DVT in two, central venous in one, and proximal arterial in one. Five children were diagnosed with systemic lupus erythematosus (SLE), including two children for whom thrombosis was the presenting sign of SLE. The remaining 14 children were diagnosed with the antiphospholipid antibody (APA) syndrome. The APA syndrome was manifest by venous or arterial thrombosis in association with a positive LA; positive anticardiolipin antibodies and a fine, speckled antinuclear antibody (ANA) pattern were additionally found in the majority of children. Approximately one‐half of the children with SLE or the APA syndrome had a pulmonary embolus, and one‐half developed recurrent thrombosis. Oral anticoagulation with coumadin to achieve an INR of >2.0 prevented thrombosis recurrence. The recognition of a LA in children with thrombosis necessitates evaluation for SLE, APA, and other autoantibodies. © 1995 Wiley‐Liss, Inc.
Reliability of automated platelet counts: Comparison with manual method and utility for prediction of clinical bleeding
Authors: Lawrence Jeffry B. , Yomtovian Roslyn A. , Dillman Christine , Masarik Susan R. , Chongkolwatana Viroje , Creger Richard J. , Manka Agnes , Hammons Terry , Lazarus Hillard M.
Published: February 2007

The 20 × 109/L (20,000/μl) threshold for prophylactic platelet transfusion may be unnecessarily high. The widespread use of this threshold may reflect lack of confidence in the reliability of low platelet counts. We evaluated the performance of automated platelet counts and their relation to clinical bleeding. First, we prepared serial blood dilutions with “target” platelet counts from 2 to 40 × 109/L For the 48 measurements on 2 × 109/L “target” dilutions, values of 1 or 2 × 109/L were obtained with the Sysmex NE‐8000 analyzer (mean 1.44 × 109/L; SD 0.31 × 109/L). Similarly, for 5 × 109/L “target” counts, automated counts were 3‐6 × 109/L (mean 4.42 × 109/L; SD 0.18 × 109/L). Similar results were observed with all other “target” levels, with coefficients of variation (CV) from 6.39% to 7.71% with 10‐40 × 109/L “target” values. Secondly, we compared triplicate automated and manual platelet counts on thrombocytopenic patients with platelet counts from 4–30 × 109/L. The triplicate automated platelet counts differed by no more than 5 × 109/L among themselves, whereas the manual counts varied by as much as 30 × 109/L. Mean platelet counts: automated, 14.40 × 109/L (CV 10.12%); manual, 16.48 × 109/L (CV 30.39%) (P = 0.038 for counts; P < 0.001 for CV). Finally, we prospectively evaluated bleeding in thrombocytopenic patients (1,809 patient‐days of observation). Univariate and multivariate logistic regression analysis revealed highly significant correlations between the automated platelet count and major and minor bleeding manifestations. Thus, automated platelet counts are highly reliable and accurately predict clinical bleeding. The use of automated analyzers should facilitate improved prophylactic platelet transfusion protocols.
Durable complete remission of macroglobulinemia after splenectomy: A report of two cases and review of the literature
Authors: Humphrey Jeffrey S. , Conley C. Lockard
Published: February 2007

Two patients with macroglobulinemia (monoclonal lgM in the serum) and massive splenomegaly were incapacitated by progressive disease refractory to standard chemotherapy. In each case, palliative splenectomy was followed by a prompt, complete, and unexpected clinical remission with disappearance from the serum of the monoclonal IgM component. One patient remains free of disease 12 years after splenectomy. The other patient remained free of detectable macroglobulinemia for 13 years after splenectomy. A review of the literature revealed other cases of remission of macroglobulinemia attributable to splenectomy alone. Data in humans and animals suggest that the spleen may facilitate IgM secretion by normal and malignant B lymphocytes. Splenectomy should be considered a possible treatment option for patients with massive splenomegaly and macroglobulinemia who progress on chemotherapy. © 1995 Wiley‐Liss, Inc.
Decreased protein C inhibitor after percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction
Authors: Tanigawa Motoaki , Wada Hideo , Minamikawa Kouzou , Wakita Yoshihiro , Nagaya Shozaburo , Mori Tateyuki , Tamaki Shigehisa , Nishikawa Hideo , Kakuta Yutaka , Nakano Takeshi , Hayashi Tatsuya , Suzuki Koji , Shiku Hiroshi
Published: February 2007

Plasma thrombin‐antithrombin 111 complex (TAT), FDP‐D‐dimer, activated protein C (APC)‐protein C inhibitor (PCI) complex, and tissue type plasminogen activator (t‐PA), PA inhibitor‐1 (PAI‐I) were significantly increased in patients with acute myocardial infarction (AMI) at onset. These patients exhibited a hypercoagulable state and protein C activation at onset. The plasma PCI level at onset of AMI was within the normal range, but was significantly decreased after percutaneous transluminal coronary angioplasty (PTCA). After PTCA, plasma t‐PA, FDP‐D‐dimer, and plasmin‐a,‐plasmin inhibitor were increased but APC‐PCI complex and TAT were not. The decrease in PCI after PTCA may have been caused by the activation of fibrinolysis. PCI may play an important role in the inhibition of fibrinolysis in stimulated or damaged endothelial cells. These findings suggest that the protein C pathway plays an important role in the onset of AMI and after PTCA. © 1995 Wiley‐Liss, Inc.
Hemoglobin F‐Cincinnati, α2Gγ2 41(C7) Phe → Ser in a newborn with cyanosis
Authors: Kohli‐Kumar Mudra , Zwerdling Theodore , Rucknagel Donald L.
Published: February 2007

A term infant presented with mild cyanosis without evidence of hypoxia. Cardiopulmonary disease, polycythemia, and methemoglobinemia were excluded. Standard hemoglobin electrophoresis, including isoelectric focusing, were normal. However, by reversephase C4 HPLC, an abnormal globin chain was detected. Analysis of tryptic peptides and amino acid sequence showed that the patient had an amino acid substitution Phe→Ser at residue 41(C7) in the Gγ chain. This was confirmed by DNA sequencing that demonstrated a point mutation at the expected site in exon 2 of the Gγ gene, accounting for the appropriate change in the codon. This substitution, hemoglobin F‐Cincinnati, α2 γ2 41(C7) Phe→Ser, not previously described, presumably decreased oxygen affinity of the hemoglobin. This substitution is very near the heme group and the α1 β2 interface and, hence, in a crucial area of the globin chain. Abnormalities of γ globin chains tend to be overlooked due to their transient presence and trivial clinical symptomatology, or due to “in utero” selection when physiologically abnormal. Mutant hemoglobins with altered oxygen affinity should be included in the differential diagnosis of newborns presenting with cyanosis, in whom all common causes have been excluded. © 1995 Wiley‐Liss, Inc.
Heterogeneity of the aggregation response of human platelets to arginine vasopressin
Authors: Lachant Neil A. , Smith Mary R. , Xie Zi‐Jian , Romani William R. , Zhou Jane
Published: February 2007

Previous reports have alluded to variability in the aggregation response of normal human platelets to the neuropeptide arginine vasopressin (AVP). Since it has not been well documented, the current studies were undertaken to characterize this response. AVP (1‐100 nM) produced a concentration‐dependent aggregation response. Although the aggregation response to 100 nM AVP did not correlate with age or sex, there was a bimodal response distribution based on the presence or absence of a second wave of aggregation. In kinetic studies, the apparent km of AVP was 18.3 ± 5.4 nM. There was a significant inverse relationship between the maximal aggregation response to 100 nM AVP and the km (r = −0.82). One hundred nanomolar AVP increased the intracellular calcium concentration of platelets by 406 ± 120 nM in calcium free buffer and by 658 ± 233 nM in the presence of 1.0 nM CaCl2. The aggregation response to 100 nM AVP correlated most strongly with the transmembrane influx of calcium (r = 0.84). In individuals whom 100 nM AVP was able to generate a second wave of aggregation, the selective protein kinase C inhibitor bis‐indolylmaleimide significantly decreased the platelet aggregation response. Thus, there is significant heterogeneity in the aggregation response of normal human platelets to AVP. Based on our kinetic studies and the effects of PKC inhibition on the aggregation response to AVP, we would hypothesize that the variability of the aggregation response of normal human platelets to AVP is related to a polymorphism of the platelet AVP V1 receptor. © 1995 Wlley‐Liss, Inc.
Leu110Pro substitution in the RhD polypeptide is responsible for the DVII category blood group phenotype
Authors: Rouillac Christelle , Le Van Kim Caroline , Beolet Marylise , Cartron Jean‐Pierre , Colin Yves
Published: February 2007

The nucleotide sequence of the RhD transcripts from the reticulocytes of three unrelated variants with the DVII category blood group phenotype has been determined. Our results indicate that the expression of the low frequency antigen Rh40 and the lack of epD8 at the surface of these variant RhD positive red cells are associated with a single point mutation, T329C, in exon 2 of the RHD gene. This nucleotide polymorphism results in a leucine to proline substitution at amino acid position 110 of the RhD polypeptide. © 1995 Wiley‐Liss, Inc.
Safety of high doses of a monoclonal antibody‐purified factor IX concentrate
Authors: Warrier Indira , Kasper Carol K. , White Gilbert C. , Shapiro Amy D. , Bergman Garrett E.
Published: February 2007

This report summarizes safety and efficacy information among patients treated with high doses (>75 U/kg) of a monoclonal antibody‐purified factor IX concentrate [coagulation factor IX (human) monoclonal antibody purified)] in two clinical trials. One hundred infusions of this factor IX concentrate at doses >75 U/kg were administered to 35 patients, six of whom had experienced thrombotic complications during previous treatment with prothrombin complex concentrate. Hemostasis in all patients was rated as “excellent,” and there were no thrombotic complications. © 1995 wiley‐Liss, Inc.
Pretreatment fibrinogen levels are associated with response to chemotherapy in patients with small cell carcinoma of the lung: Department of veterans affairs cooperative study 188
Authors: Meehan Kenneth R. , Zacharski Leo R. , Moritz Thomas E. , Rickles Frederick R.
Published: February 2007

Small cell carcinoma of the lung (SCCL) responds commonly to combination chemotherapy but resistance to therapy follows. Prior reports have suggested that a relationship may exist between plasma fibrinogen levels and response to therapy in SCCL. This study was designed to determine the possible predictive value of the fibrinogen level for tumor response (chemoresistance) in SCCL. Pretreatment fibrinogen levels were correlated with outcome and response to therapy in a cohort of 119 previously untreated patients with SCCL who were admitted to VA Cooperative Study 188. Higher pretreatment fibrinogen levels at diagnosis correlated significantly with more advanced stage of disease at entry (P 0.001) and with reduced overall survival (P 0.030). In addition, higher pretreatment fibrinogen levels were correlated significantly with a reduced likelihood of achieving subsequent disease regression with combination chemotherapy (P = 0.005). Because several clinical trials have shown that anticoagulant therapy improves tumor response rates and survival of SCCL, we postulate that tumor cell thrombin generation not only promotes SCCL growth but may also be primarily responsible for both increased fibrinogen levels and for resistance to chemotherapy. These findings provide incentive for studies of thrombin effects on the development of multidrug esistance, and for new clinical trials of more potent and specific inhibitors of thrombin that may further improve tumor response and survival in SCCL. ©1995 Wiley‐Liss, Inc.