bluuebunny/crossref_metadata_2025_split huggingface dataset:
Congenital dyserthropoietic anaemia other than type I to III with a peculiar erythroblastic morphology
Authors: Woessner S. , Trujillo M. , Florensa L. , Mesa M. C. , Wickramasinghe S. N. 
Published: August 2003

Abstract:Here, we report the case of a child who, since birth, showed persistent macrocytosis and elevated mean corpuscular volume of the erythrocytes. Bone marrow biopsy revealed gross disorganisation of the erythroblastic series both at the light and electron microscopic examination, with complete absence of dysplastic features in the granulocytic and megakaryocytic series. Common causes of macrocytosis were excluded. The spectrum of morphological findings were not consistent with any of the classical types of congenital dyserythropoietic anaemias (CDAs) and serological findings of CDA type II were absent. The most outstanding feature was a marked irregularity of the nuclear outline of the late erythroblasts that presented thick‐ending finger‐like projections. The combination of macrocytosis without anaemia and these morphologic erythroblastic changes have not been previously reported in the setting of classical and variant forms of CDAs.
Accumulation of γ‐globin mRNA in human erythroid cells treated with angelicin
Authors: Lampronti Ilaria , Bianchi Nicoletta , Borgatti Monica , Fibach Eitan , Prus Eugenia , Gambari Roberto 
Published: August 2003

Abstract:The aim of the present study was to determine whether angelicin is able to increase the expression of γ‐globin genes in human erythroid cells. Angelicin is structurally related to psoralens, a well‐known chemical class of photosensitizers used for their antiproliferative activity in treatment of different skin diseases (i.e., psoriasis and vitiligo). To verify the activity of angelicin, we employed two experimental cell systems, the human leukemic K562 cell line and the two‐phase liquid culture of human erythroid progenitors isolated from normal donors. The results of our investigation suggest that angelicin, compared with cytosine arabinoside, mithramycin and cisplatin, is a powerful inducer of erythroid differentiation and γ‐globin mRNA accumulation of human leukemia K562 cells. In addition, when normal human erythroid precursors were cultured in the presence of angelicin, increases of γ‐globin mRNA accumulation and fetal hemoglobin (HbF) production, even higher than those obtained using hydroxyurea, were detected. These results could have practical relevance, as pharmacologically‐mediated regulation of the expression of human γ‐globin genes, leading to HbF induction, is considered a potential therapeutic approach in hematological disorders, including β‐thalassemia and sickle cell anemia.
Successful clearance of hepatitis B virus after allogeneic stem cell transplantation: beneficial combination of adoptive immunity transfer and lamivudine
Authors: Chiba Tetsuhiro , Yokosuka Osamu , Goto Shigemasa , Fukai Kenichi , Imazeki Fumio , Shishido Hideki , Narita Mitsuro , Saisho Hiromitsu 
Published: August 2003

Abstract:We report a 38‐yr‐old male with acute lymphocytic leukemia (ALL), whose serological tests for the hepatitis B virus (HBV) before transplantation showed a chronic carrier status, and a liver biopsy specimen revealed chronic liver injury because of HBV. The patient underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his sibling who was hepatitis B surface antibody (HBsAb) positive. He had received lamivudine treatment for the prophylaxis of HBV reactivation during cytotoxic chemotherapy, and lamivudine administration continued after transplantation. Successful engraftment was documented 3 wk after PBSCT, and clearance of the hepatitis B surface antigen (HBsAg) was observed 2 months after PBSCT. Liver function tests transiently showed a mild elevation of aminotransferases on day 25, although this returned to normal after the dose escalation of the immunosuppressive agent. We presume that the combination of adoptive immunity transfer by bone marrow transplantation (BMT) from an HBsAb‐positive donor and antiviral drugs such as lamivudine is beneficial in clearing HBV in chronic carriers.
Fas ligand is not constitutively expressed in low‐grade B‐cell lymphoma and B‐lymphoblastoid cells
Authors: Grüllich Carsten , Richter Manfred , Exner Sebastian , Finke Jürgen 
Published: August 2003

Abstract:The Fas ligand (FasL) pathway is one of the two major effector mechanisms of T‐cell‐mediated cell death. FasL expression by extralymphatic tissues is thought to maintain a status of immunity. Accordingly, it has been proposed that tumor cells express FasL as a mechanism of immunologic escape. However, data regarding FasL expression in normal or neoplastic tissues remain controversial. In the present study, we investigated the expression of FasL in normal peripheral blood B lymphocytes or malignant cells of the B‐lymphocyte lineage to elucidate a possible immunologic counterattack mechanism. FasL gene expression was analyzed by reverse transcriptase polymerase chain reaction in two non‐Hodgkin's lymphoma (NHL) entities: the highly aggressive Burkitt's lymphoma (BL) and indolent NHL chronic lymphocytic leukemia (CLL). FasL expression was found to be consistently negative in all BL cell lines and purified samples from patients with CLL. FasL is not constitutively expressed in normal peripheral blood or neoplastic B lymphocytes making the Fas counterattack, as described for gastrointestinal cancer, unlikely as a mechanism of immunologic escape of lymphoma cells.
Elevation of extracellular adenosine mobilizes haematopoietic progenitor cells and granulocytes into peripheral blood and enhances the mobilizing effects of granulocyte colony‐stimulating factor
Authors: Hofer M. , Weiterová L. , Vacek A. , Znojil V. , Pospíšil M. , Vácha J. 
Published: August 2003

Abstract:We tested the capabilities of drugs elevating extracellular adenosine and of granulocyte colony‐stimulating factor (G‐CSF), given alone or in combination, to mobilize haematopoietic progenitor cells for granulocytes and macrophages (GM‐CFC) and granulocytes into peripheral blood. Elevation of extracellular adenosine was induced by joint administration of dipyridamole (DP), a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP) serving as an adenosine prodrug. DP + AMP, G‐CSF or all these drugs in combination were administered either singly or repeatedly in a 4‐d treatment regimen. Elevation of extracellular adenosine was found to mobilize significantly both GM‐CFC and granulocytes after both single and repeated administration of DP + AMP. These results show that the elevation of extracellular adenosine presents a potent mechanism for mobilization of GM‐CFC and granulocytes into the blood. When the combination of DP + AMP + G‐CSF was given under the 4‐d regimen, the mobilizing effects of its administration were additive when compared with those of DP + AMP alone or G‐CSF alone. The observed ability of the drugs elevating extracellular adenosine to enhance the mobilizing action of G‐CSF points out possible practical utilization of the findings presented here. This conclusion is further supported by the results of an additional experiment which indicate that blocking of haemodynamic side effects of drugs elevating extracellular adenosine by noradrenaline does not suppress their mobilizing effects.
CD8+ chronic lymphocytic leukemia: an extensive characterization of a bizarre hybrid neoplasia
Authors: Richaud‐Patin Y. , Piedras J. , Carrillo‐Maravilla E. , López‐Karpovitch X. , Llorente L. 
Published: August 2003

Abstract:Atypical chronic lymphocytic leukemia (CLL) expressing the CD8 antigen have a frequency of less than 0.5% of all cases, however, they are not yet been fully characterized. Herein a CD8+ CLL case was extensively studied. Besides the classical CLL antigen expression, an unusual presence of surface markers such as CD11c, CD56, and CD154 was observed. Moreover, gene expression of chemokine receptors belonging to the CCR family were clearly evidenced as well as mRNA for both, Th1 and Th2 cytokines. Likewise, granzyme A, B and perforin gene expression, cytotoxic T cell or NK enzymes were found. The intricate profile of membrane molecules and gene expression suggest that it could be favorable, rather than deletereous, for the maintainance of the neoplastic process.
A multicenter, open, non‐comparative, phase II study of the combination of cladribine (2‐chlorodeoxyadenosine), cytarabine, and G‐CSF as induction therapy in refractory acute myeloid leukemia – a report of the Polish Adult Leukemia Group (PALG)
Authors: Wrzesień‐Kuś A. , Robak T. , Lech‐Marańda E. , Wierzbowska A. , Dmoszyńska A. , Kowal M. , Hołowiecki J. , Kyrcz‐Krzemień S. , Grosicki S. , Maj S. , Hellmann A. , Skotnicki A. , Je˛drzejczak W. , Kuliczkowski K. 
Published: August 2003

Abstract:Objectives: To evaluate the efficacy and toxicity of cladribine (2‐chlorodeoxyadenosine, 2‐CdA), cytarabine (Ara‐C), and granulocyte‐colony stimulating factor (G‐CSF) (CLAG) regimen in refractory acute myeloid leukemia (AML) in the multicenter phase II study.Methods: The induction chemotherapy consisted of 2‐CdA 5 mg/m2, Ara‐C2 g/m2, and G‐CSF. In the case of partial remission (PR), a second CLAG was administered. Patients in complete remission (CR) received two consolidation courses based on HD Ara‐C, mitoxantrone or idarubicine, with or without 2‐CdA.Results: Fifty‐eight patients from 11 centers were registered; 50 primary resistant and eight early relapsed (CR1 < 6 months). CR was achieved in 29 (50%) patients, 19 (33%) were refractory, and 10 (17%) died early. Forty of 50 primary resistant patients received daunorubicin (DNR) and Ara‐C as the first‐line induction therapy (DA‐7), 10 received additional 2‐CdA (DAC‐7). The CR rates after CLAG were 58% and 10%, respectively in each group (P = 0.015). Five of six patients with myelodysplastic syndrome (MDS)/AML achieved CR. Hematologic toxicity was the most prominent toxicity of this regimen. The overall survival (OS, 1 yr) for the 58 patients as a whole, and the 29 patients in CR were 42% and 65%, respectively. Disease‐free survival (DFS, 1 yr) was 29%. Only first‐line induction treatment with DA‐7 significantly influenced the probability of CR after CLAG. None of the analyzed factors significantly influenced DFS and OS.Conclusion: CLAG regimen has significant anti‐leukemic activity and an acceptable toxicity in refractory AML. The addition of 2‐CdA to the first‐line induction treatment may worsen the results of salvage with CLAG. The high CR rate in patients with MDS preceding AML deserves further observation.
Use of plasma DNA in detection of loss of heterozygosity in patients with multiple myeloma
Authors: Ahmed Maha , Giles Francis , Joe Youngson , Weber Donna M. , Jilani Iman , Manshouri Taghi , Giralt Sergio , Lima Marcos De , Keating Michael , Albitar Maher 
Published: August 2003

Abstract:Background: Deletions or structural abnormalities in chromosomes 11 and 13 have been shown to be important in predicting clinical behavior in patients with multiple myeloma (MM). However, cytogenetic analysis in MM is frequently difficult because of poor yield of informative metaphases and the disease is frequently patchy, which complicates fluorescent in situ hybridization studies.Objectives: The purpose of this study was to explore the potential of using peripheral plasma DNA for the detection of loss of heterozygosity (LOH) in chromosomes 11 and 13 in patients with MM.Methods: Peripheral blood (PB) plasma of 81 patients with MM, was used as a source of DNA for the detection of LOH at chromosomes 13q14 (D13S319 and D13AFMaw301wb5), and 11q21 (D11S2179) using polymerase chain reaction.Results: Only 62 of the studied patients were informative for the two 13q microsatellite markers and 16 (26%) of these patients showed LOH. Only seven (11%) of 61 patients with informative D11S2179 microsatellite maker showed LOH. Purified plasma cells (PCs) from six bone marrow (BM) samples using anti‐CD138‐coated magnetic beads showed identical results to those detected in DNA isolated from PB plasma. Three patients with LOH underwent autologous BM transplantation, and two of three reverted to a normal state (no LOH) after transplantation. Seven of the patients with 13q LOH in PB plasma had <10% PCs (PCs) in their BM at the time of testing.Conclusion: PB plasma appears to be enriched by tumor‐specific DNA and can be used to detect chromosomal abnormalities in patients with MM. Further studies are needed to establish the clinical relevance of this approach in comparison with other techniques.
A clinical and molecular study of a Bedouin family with dysmegakaryopoiesis, mild anemia, and neutropenia cured by bone marrow transplantation
Authors: Tamary H. , Yaniv I. , Stein J. , Dgany O. , Shalev Z. , Shechter T. , Resnitzky P. , Shaft D. , Zoldan M. , Kornreich L. , Levy R. , Cohen A. , Moser R. A. , Kapelushnik J. , Shalev H. 
Published: August 2003

Abstract:Objectives: Familial thrombocytopenia is a relatively rare and heterogeneous group of clinical and genetic syndromes of unknown etiology. Recently, mutations in a few hematopoietic transcription factors were implicated in dysmegakaryopoiesis with and without dyserythropoietic anemia. The aim of the present study was to describe the clinical and hematologic picture of members of a Bedouin family with severe congenital thrombocytopenia associated with neutropenia and anemia and to determine the possible involvement of hematopoietic transcription factor genes in their disease.Patients and methods: Four members of a Bedouin family presented with severe bleeding tendency, including intracranial hemorrhage in three. Three of the four were successfully treated with allogenic human leukocyte antigen (HLA)‐matched bone marrow transplants. Measurements of serum erythropoietin and thrombopoietin levels, bone marrow electron microscopy, and megakaryocytic colony were grown for each patient in addition to DNA amplification and single‐strand conformation polymorphism of each exon of the NF‐E2, Fli‐1, FOG‐1, and Gfi‐1b in genes.Results: Bone marrow studies revealed dysmegakaryopoiesis and mild dyserythropoiesis. A low number of bone marrow megakaryocyte colony‐forming units was found, as well as a slightly elevated serum thrombopoietin level. No mutation was identified in any of the transcription factor genes examined.Conclusions: A unique autosomal recessive bone marrow disorder with prominent involvement of megakaryocytes is described. Defects were not identified in transcription factors affecting the common myeloid progenitor.
The angioregulatory phenotype of native human acute myelogenous leukemia cells: influence of karyotype, Flt3 abnormalities and differentiation status
Authors: Glenjen Nils , Hovland Randi , Wergeland Line , Wendelbo Øystein , Ernst Peter , Bruserud Øystein 
Published: August 2003

Abstract:Introduction: The cytogenetic abnormalities and the response to induction therapy have been regarded as the most important prognostic parameters in acute myelogenous leukemia (AML) patients. Recent studies have demonstrated that internal tandem duplications and specific D‐835 point mutations of the Flt3 gene, as well as the angioregulatory phenotype represent additional adverse prognostic factors. The aim of the study was to investigate possible associations between genetic abnormalities, differentiation status and angioregulatory phenotype in native human AML blasts.Method: Native AML blasts derived from consecutive patients were cultured in vitro and concentrations of angioregulatory molecules determined in the supernatants.Results: Most patients released at least two different angioregulatory mediators. Pro‐angiogenic interleukin 8 (IL8) was released at relatively high levels for most patients, many of these patients showed additional release of pro‐angiogenic vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). High release of anti‐angiogenic IL12 was associated with high release of pro‐angiogenic IL8 and VEGF. Furthermore, patients with D‐835 mutations showed increased IL12 release, whereas patients with normal karyotype had decreased HGF release. Myelomonocytic differentiation was associated with IL18 release and CD34 expression with low IL12 release.Conclusion: Our results suggest that native human AML blasts have a pro‐angiogenic phenotype. Although the investigated genetic abnormalities are associated with variation in the in vitro release of angioregulators, these differences are relatively small and do not quantitatively involve the most important IL8 release. It therefore seems unlikely that this phenotypic variation can explain the prognostic impact of the genetic abnormalities.
Review article: the role of rebamipide in the management of inflammatory disease of the gastrointestinal tract
Authors: Genta R. M. 
Published: August 2003

SummaryRebamipide stimulates the generation of endogenous prostaglandins in the gastric mucosa and is reported to accelerate ulcer healing. This review discusses whether rebamipide can prevent Helicobacter pylori infection, reduce inflammation, accelerate healing after eradication, promote ulcer healing, and prevent progression of preneoplastic lesions. Furthermore, we evaluate its usefulness in other inflammatory conditions of the gastrointestinal tract. We conclude that rebamipide is an important candidate for long‐term suppression of gastro‐intestinal inflammation, praticularly if reducing the complications of H. pylori infection without eradicating the organism becomes accepted. If its ability to accelerate mucosal normalization is confirmed, rebamipide could be added to eradication regimens. Little information exists on whether such therapy could help limit the development of pre‐neoplastic lesions. In light of the dearth of effective drugs to control inflammation in idiopathic inflammatory bowel disease, the potential of any promising new and safe compound deserves to be fully explored. The next step is to devise a targeted plan of translational research, so that results from the bench may be used to design rigorously controlled international clinical trials.
Review article: rebamipide and the digestive epithelial barrier
Authors: Matysiak‐Budnik T. , Heyman M. , Mégraud F. 
Published: August 2003

SummaryRebamipide exerts a positive effect on the digestive epithelial barrier by reinforcing its integrity in normal and in inflammatory conditions, and by normalizing the macromolecular transport across this barrier, increased by Helicobacter infection. Moreover, in mice, rebamipide is capable of diminishing allergic sensitization and of counteracting the inhibitory effect of Helicobacter pylori on oral tolerance to dietary antigens. These properties of rebamipide could explain its anti‐inflammatory activity with respect to the digestive mucosa and could provide protection against allergic sensitization to foreign antigens in susceptible individuals.
Early Middle Miocene broken foreland development in the southern Central Andes: evidence for extension prior to regional shortening
Authors: Dávila Federico M. , Astini Ricardo A. 
Published: August 2003

AbstractMost authors suggest that the main contraction phases in the southern Central Andes started in the Late Miocene. Along the flat‐slab segment, deformation has progressively involved basement and a broken foreland has developed. Recent work suggests that construction of the Andes by late Neogene shortening may have been controlled by lithospheric thinning and crustal structure generated during mid‐Tertiary times in the Southern and Central Andes. Exposures at the eastern border of the Famatina Ranges in western Argentina in the flat‐slab segment document basement involved extension of approximately this age. The Del Abra Formation, the lower unit of a major Andean synorogenic cycle (Angulos Group), reveals a distinct and previously unrecognized early Middle Miocene tectonic event. This is suggested by a 505‐m‐thick thinning‐ and fining‐upward megasequence. Dominantly conglomeratic facies record a continuous progression from fault‐scarp‐related high‐gradient colluvium to relatively distal terminal‐fan facies. The fining–thinning upward megasequence characterizes progressive scarp backstepping and decreasing relief after active extension. Interpretation of the stratigraphic fill and the associated structure (high‐angle hinterland‐dipping fault) favours tectonic inversion of an originally normal fault. This allows reappraisal and new understanding of the early‐stage architecture of the Central Andean foreland. Early Middle Miocene extension may have had an important bearing on the later evolution of the broken foreland.
Synclinal‐horst basins: examples from the southern Rio Grande rift and southern transition zone of southwestern New Mexico, USA
Authors: Mack Greg H. , Seager William R. , Leeder Mike R. 
Published: August 2003

AbstractIn areas of broadly distributed extensional strain, the back‐tilted edges of a wider than normal horst block may create a synclinal‐horst basin. Three Neogene synclinal‐horst basins are described from the southern Rio Grande rift and southern Transition Zone of southwestern New Mexico, USA. The late Miocene–Quaternary Uvas Valley basin developed between two fault blocks that dip 6–8° toward one another. Containing a maximum of 200 m of sediment, the Uvas Valley basin has a nearly symmetrical distribution of sediment thickness and appears to have been hydrologically closed throughout its history. The Miocene Gila Wilderness synclinal‐horst basin is bordered on three sides by gently tilted (10°, 15°, 20°) fault blocks. Despite evidence of an axial drainage that may have exited the northern edge of the basin, 200–300 m of sediment accumulated in the basin, probably as a result of high sediment yields from the large, high‐relief catchments. The Jornada del Muerto synclinal‐horst basin is positioned between the east‐tilted Caballo and west‐tilted San Andres fault blocks. Despite uplift and probable tilting of the adjacent fault blocks in the latest Oligocene and Miocene time, sediment was transported off the horst and deposited in an adjacent basin to the south. Sediment only began to accumulate in the Jornada del Muerto basin in Pliocene and Quaternary time, when an east‐dipping normal fault along the axis of the syncline created a small half graben. Overall, synclinal‐horst basins are rare, because horsts wide enough to develop broad synclines are uncommon in extensional terrains. Synclinal‐horst basins may be most common along the margins of extensional terrains, where thicker, colder crust results in wider fault spacing.