bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accurate and rapid prenatal diagnosis of the most frequent East Mediterranean β‐thalassemia mutations
Authors: Naja R.P. , Kaspar H. , Shbaklo H. , Chakar N. , Makhoul N.J. , Zalloua P.A. 
Published: March 2004

Abstractβ‐Thalassemia is the most common genetic disorder in the Lebanese population. Of the 200 different mutations in the β‐globin gene that leads to thalassemia, the IVSI‐110 (29.87%), IVSI‐6 (20.74%), IVSI‐1 (14.07%), IVSII‐1 (9.13%), Cd29 (9.13%), and Cd30 (3.95%) mutations are the most frequent among Lebanese thalassemic patients. These mutations are also present at high frequencies in the East Mediterranean region. Due to this high prevalence of certain β‐thalassemia mutations, a rapid technique for the prenatal diagnosis of these mutations was implemented. The technique used is based on Real‐Time PCR quantification and melting curve analysis of the amplified fragment using the LightCycler. The DNA samples used for amplification were obtained from CVS or amniotic fluid. Six mutations were easily and efficiently detected using only 3 sets of probes. With this method, mutant genotypes can be easily distinguished from normal alleles. In prenatal diagnosis, the accuracy and the speed of testing are paramount. The method of prenatal β‐thalassemia mutations detection described here is efficient and fast, with the entire procedure including DNA preparation taking less than half a workday. It is safe, does not involve radioactivity, and is accurate showing 100% concordance with conventional DNA sequencing methods. Am. J. Hematol. 75:220–224, 2004. © 2004 Wiley‐Liss, Inc.
Erythrocytosis due to bisphosphoglycerate mutase deficiency with concurrent glucose‐6‐phosphate dehydrogenase (G‐6‐PD) deficiency
Authors: Hoyer James D. , Allen Steven L. , Beutler Ernest , Kubik Kathleen , West Carol , Fairbanks Virgil F. 
Published: March 2004

AbstractA 28‐year‐old asymptomatic male of Iranian Jewish (Meshadi) heritage was found on routine exam to have an erythrocytosis (RBC = 6.22 × 1012/l, Hgb = 19.2 g/dl, Hct = 58.9%). Splenomegaly was absent on physical exam. There was no family history of erythrocytosis. His oxygen dissociation curve was left‐shifted with a p50 of 19 mmHg (normal = 25–32 mmHg). Hemoglobin electrophoresis showed no abnormalities. DNA sequencing of the hemoglobin β globin gene and both α globin genes did not reveal a mutation. A 2,3‐bisphosphoglycerate (BPG) level was markedly decreased at 0.3 μmol/g Hb (normal = 11.4–19.4 μmol/g Hb). The patient's bisphosphoglycerate mutase (BPGM) enzyme activity was also markedly decreased at 0.16 IU/g Hb (normal = 4.13–5.43 IU/g Hb). A red cell enzyme panel revealed a markedly decreased G‐6‐PD level (0.3 U/g Hb, normal = 8.6–18.6 U/g Hb). His parents and a brother were also available for evaluation. Both parents showed normal 2,3‐BPG levels but BPGM activity approximately 50% of normal. Paradoxically, the brother showed normal BPGM activity but a slightly decreased 2,3‐BPG level. All family members had markedly decreased G‐6‐PD activity. DNA sequencing of the BPGM gene showed the propositus to be homozygous for 185 G→A, Arg 62 Gln in exon 2. Thus, the erythrocytosis in this patient is secondary to low 2,3‐BPG levels, due to a deficiency in BPG mutase. This appears due to consanguinity within this family. Am. J. Hematol. 75:205–208, 2004. © 2004 Wiley‐Liss, Inc.
Cutaneous B‐cell lymphoma: Pathological spectrum and clinical outcome in 51 consecutive patients
Authors: Sah A. , Barrans S.L. , Parapia L.A. , Jack A.S. , Owen R.G. 
Published: March 2004

AbstractThe clinical behavior and optimal treatment of patients presenting with skin infiltration by B‐cell lymphoma have not been established. To clarify this we assessed the clinical and laboratory features of 51 patients presenting with cutaneous infiltration by B‐cell lymphoma. Follow‐up data was available for 46 patients with a median age of 68 years (range 16–89 years) and a median follow‐up of 32.5 months (range 5–123 months). Thirty‐three of 51 (65%) patients had diffuse large B‐cell lymphoma (DLBCL), and 15/51 (29%) had marginal zone lymphoma (MZL). The remaining 3 patients had follicular lymphoma, CLL, and post‐transplant lymphoproliferative disease. Of the 33 patients with DLBCL, follow‐up was available in 29; 24/29 (83%) had primary cutaneous disease, which was unifocal in 17/24 (71%). Following treatment, 8/24 (33%) of the primary cases relapsed. Of the 8 who relapsed, 7 had received local forms of treatment only. Follow‐up data was available in 14/15 patients with MZL. 11/14 (79%) had primary cutaneous disease, which was unifocal in 8 (73%). Following treatment, 4 of these cases relapsed (36%); all had received local therapy only. It is evident from this study that a significant proportion (∽20%) of patients who present with cutaneous infiltration by B‐cell lymphoma have systemic disease. Staging is therefore mandatory in these patients. Approximately 1/3 patients with primary cutaneous DLBCL or MZL ultimately relapse, and relapse rates appear higher in thosepatients receiving local therapy only. Systemic or combined modality therapy may therefore be the most appropriate treatment at presentation. This should be assessed prospectively in randomized trials. Am. J. Hematol. 75:195–199, 2004. © 2004 Wiley‐Liss, Inc.
Blastic mantle cell lymphoma developing concurrently in a patient with chronic myelogenous leukemia and a review of the literature
Authors: Rodler Eve , Welborn Jeanna , Hatcher Sandra , Unger Katherine , Larkin Edward , Gumerlock Paul H. , Wun Theodore , Richman Carol 
Published: March 2004

AbstractNon‐Hodgkin's lymphoma (NHL) occurring as a synchronous malignancy with chronic myelogenous leukemia (CML) is rare. To our knowledge, this is the first case reported of a patient who developed mantle cell lymphoma (MCL) after therapy with imatinib mesylate for CML. After a 3‐year history of CML, the patient developed a lymphocytosis associated with diarrhea, anorexia, and weight loss. Imaging studies revealed abdominal adenopathy and extensive lymphomatous infiltration of the liver, stomach, pancreas, and kidneys. Flow cytometric and cytogenetic studies were consistent with MCL. Fluorescence in situ hybridization (FISH) of the bone marrow revealed a genetically distinct lymphoid neoplasm rather than an extramedullary blast crisis of CML. The development of lung cancer, prostate cancer, CML and MCL in this patient suggests a genetic predisposition, although other factors, including environmental exposures and therapy with imatinib mesylate could have had a contributory or synergistic role in the development of MCL. Am. J. Hematol. 75:231–238, 2004. © 2004 Wiley‐Liss, Inc.
The Mexican schedule to conduct allogeneic stem cell transplantation is related to a low risk of cytomegalovirus reactivation and disease
Authors: Ruiz‐Argüelles Guillermo J. , Rangel J. David Gómez , Ponce‐de‐León Samuel , González‐Déctor Laura , Reyes‐Núñez Virginia , Garcés‐Eisele Javier 
Published: March 2004

AbstractThe prevalence of cytomegalovirus (CMV) reactivation and disease after non‐myeloablative stem cell transplantation is largely unknown. Using fludarabine combined with alemtuzumab or antithymocyte globulin in the conditioning regimen, some authors have found increased prevalences of CMV disease, whereas other authors using different schedules have observed decreased prevalences. In a group of 17 individuals allografted using the Mexican conditioning regimen, which employs fludarabine, cyclophosphamide, and busulfan, we assessed CMV reactivation, morbidity, and mortality. Before transplant, IgG anti‐CMV antibodies were found in 11 patients and in 10 donors; in 8 cases, both donor and patient had IgG anti‐CMV antibodies. In only one case (6%) was CMV mRNA identified 30 days after the allograft during grade IV acute graft‐versus‐host disease. CMV reactivation, disease, and mortality were very low using our non‐myeloablative stem cell transplantation schedule, which has been shown to be useful for allografting with minimal toxicity and reduced costs. Am. J. Hematol. 75:200–204, 2004. © 2004 Wiley‐Liss, Inc.
Favorable early response of secondary chronic myeloid leukemia to imatinib
Authors: Waldman Dalia , Weintraub Michael , Freeman Arnold , Neumann Yoram , Rechavi Gideon , Toren Amos 
Published: March 2004

AbstractSecond malignant neoplasms are gradually becoming a recognized long‐term complication of successful cancer treatment, and they usually respond poorly to conventional therapy and have an unfavorable outcome. Chronic myeloid leukemia (CML) is a clonal panmyelopathy, rarely seen in children with a specific cytogenetic aberration—the Philadelphia chromosome. The translocation generates an aberrant tyrosine kinase, which drives the malignant process in CML and which is also the molecular target for successful treatment of CML with imatinib. It is also exceedingly rare as a secondary malignant neoplasm in both adults and children. We report two cases of secondary CML. The first occurred after successful treatment for nasopharyngeal carcinoma in a child, and the second after treatment for lymphoma in an adolescent. Both patients had an excellent response to treatment with imatinib and attained complete cytogenetic remissions. We conclude that secondary CML may respond favorably to treatment with imatinib. Am. J. Hematol. 75:217–219, 2004. © 2004 Wiley‐Liss, Inc.
Scrotal ulceration during induction therapy of acute promyelocytic leukemia with ATRA
Authors: Pavithran Keechilat , Arjun Rajalakshmi , Aruna Raman , Thomas Mathew 
Published: March 2004

Abstractall‐trans‐Retinoic acid (ATRA) has been shown to improve survival in patients with acute promyelocytic leukemia (APML). It is a well‐tolerated drug except for the serious side effect of ATRA syndrome. Dryness of the skin, cheilitis, and xerostomia are the common mucocutaneous side effects. Occurrence of scrotal ulceration is very rare. We report a 13‐year‐old boy who had scrotal ulceration caused by ATRA during the induction therapy of APML. Am. J. Hematol. 75:260–261, 2004. © 2004 Wiley‐Liss, Inc.
Identification of mutations in TCOF1: Use of molecular analysis in the pre‐ and postnatal diagnosis of Treacher Collins syndrome
Authors: Dixon Jill , Ellis Ian , Bottani Armand , Temple Karen , Dixon Michael James 
Published: March 2004

AbstractTreacher Collins syndrome (TCS) is an autosomal dominant disorder of facial development, which results from mutations in TCOF1. TCS comprises conductive hearing loss, hypoplasia of the mandible and maxilla, downward sloping palpebral fissures and cleft palate. Although, there is usually a reasonable degree of bilateral symmetry, a high degree of both inter‐ and intrafamilial variability is characteristic of TCS. The wide variation in the clinical presentation of different patients, together with the fact that more than 60% of cases arise de novo, can complicate the diagnosis of mild cases and genetic counselling. In the current study, we describe how molecular techniques have been used to facilitate pre‐ and postnatal disease diagnoses in 13 TCS families. © 2004 Wiley‐Liss, Inc.
CDKN1C mutation in Wiedemann–Beckwith syndrome patients reduces RNA splicing efficiency and identifies a splicing enhancer
Authors: Lew Jocelyne M. , Fei Yan Ling , Aleck Kirk , Blencowe Benjamin J. , Weksberg Rosanna , Sadowski Paul D. 
Published: March 2004

AbstractWiedemann–Beckwith syndrome (WBS) is a human overgrowth disorder that is accompanied by an increased risk of embryonal tumors and is associated with dsyregulation of the imprinting of genes in chromosome 11p15.5. Maternally inherited mutations in the imprinted CDKN1C gene are known to be associated with WBS. We have identified a novel mutation in several members of a large family affected by WBS. The mutation is a G → T change in a run of seven G's near the 5′ splice site of intron 3. All obligate carriers and affected individuals carry the mutation, and in each affected case, the allele was inherited maternally, strongly suggesting a role in causing WBS. The mutation is located in a poly‐G tract in the intron; intronic G‐rich sequences in other genes have been shown to have a role in promoting splicing. In transfected 293HEK cells, we found that the G → T mutation reduced splicing efficiency. Mutation of all seven G's in the poly‐G tract further reduced splicing efficiency, supporting a role for the G‐tract as a splicing enhancer. The fibroblasts of one affected patient showed a similar reduction in splicing efficiency. Maternal monoallelic expression of CDKN1C was verified in this patient cell line. However, the total amount of spliced message was not reduced by the mutation in spite of the reduced efficiency of splicing. We discuss the possible role of the splicing defect in the pathogenesis of WBS in this pedigree. © 2004 Wiley‐Liss, Inc.
Isolated congenital anosmia with morphologically normal olfactory bulb in two Iranian families: A new clinical entity?
Authors: Ghadami Mohsen , Majidzadeh‐A Keyvan , Morovvati Saeid , Damavandi Elia , Nishimura Gen , Komatsu Kazuki , Kinoshita Akira , Najafi Mohammad‐Taghi , Niikawa Norio , Yoshiura Koh‐ichiro 
Published: March 2004

AbstractCongenital total loss of the sense of smell occurs as a part of a syndrome or isolated anosmia. Kallmann syndrome is the most well known congenital anosmia associated with hypogonadotropic hypogonadism. Isolated congenital anosmia (ICA) is a very rare condition and appears to be due to changes in the olfactory epithelium or to aplasia of the olfactory nerve, bulb, and tract. Here we report two unrelated Iranian families with ICA. One family consisted of nine affected members, and the other family contained three affected members. Clinical history, physical examination, and smell testing by intravenous injection of combined vitamins (Alinamin™, Takeda Pharmaceutical Co. Ltd., Japan) confirmed the disease in each affected member. No signs of hypogonadism or other neurological disorders were observed in any affected members. Family analysis with the complete ascertainment method under assumption of the same condition in the two families suggested that the disease is not inconsistent with an autosomal dominant mode with incomplete penetrance. The inheritance in one family appears unusual, i.e., there were no affected individuals in the third generation. When only two upper generations in the family are concerned, the segregation ratio was 0.39 ± 0.11. Male‐to‐male transmissions were observed and both sexes were affected in both families. Magnetic resonance imaging (MRI) of the olfactory bulb and sulcus revealed no evidence of morphological changes in all affected members, suggesting that these patients have either a defect in the olfactory epithelium or a functional defect in the olfactory cortex. © 2004 Wiley‐Liss, Inc.
Elevated catecholamine metabolites in patients with Costello syndrome
Authors: Gripp Karen W. , Kawame Hiroshi , Viskochil David H. , Nicholson Linda 
Published: March 2004

AbstractCostello syndrome is a rare congenital anomaly syndrome with a predisposition to specific tumors, including neuroblastoma, rhabdomyosarcoma, and transitional cell carcinoma of the bladder. The increased risk for solid tumors led to the proposal of a tumor screening protocol. A screening test for neuroblastoma consists of measuring catecholamine metabolites in urine, an assay that may also be used for diagnostic confirmation of a suspected catecholamine secreting tumor. We report eight patients with Costello syndrome with elevated catecholamine metabolites, vanillylmandelic acid (VMA) and/or homovanillic acid (HVA), in urine. Each patient had additional laboratory and/or imaging studies. None of the patients was found to have a neuroblastoma or another catecholamine secreting tumor. In two cases, the assays were performed because the patients were symptomatic with diaphoresis and hypertension, respectively, and in the other six cases the assays were performed in order to screen for neuroblastoma. The pathophysiology for the catecholamine metabolite abnormality in these patients with Costello syndrome remains unclear. However, it appears that in this patient group an elevation above the normal limit, defined as 2 standard deviations (SD) above the mean for age, is more likely to be a variant, rather than a sign of a neuroblastoma. Thus, it may be prudent not to use this assay as a screening test, and to take the frequently elevated results into consideration when interpreting diagnostic assays. © 2004 Wiley‐Liss, Inc.
Association between cytochrome P450 2D6 genotype and harm avoidance
Authors: Roberts Rebecca L. , Luty Suzanne E. , Mulder Roger T. , Joyce Peter R. , Kennedy Martin A. 
Published: March 2004

AbstractGenetic polymorphisms within the serotonergic and dopaminergic neurotransmitter systems may be associated with heightened harm avoidance and novelty seeking. It is also conceivable that polymorphisms in enzymes that mediate the metabolism of endogenous amines within the brain may influence these components of temperament. The CYP2D6 enzyme is expressed at low levels in the brain, and has been shown to mediate the formation of the neurotransmitters serotonin and dopamine from trace amines. Some 5–10% of Caucasians are CYP2D6 deficient due to inactivating mutations in the CYP2D6 gene, and are termed poor metabolizers (PMs). In this study, we investigated whether temperament varied significantly between PMs and CYP2D6 extensive metabolizers (EMs) using the Temperament and Character Inventory (TCI). CYP2D6 genotypes were determined for 121 depressed patients. Of these patients, 113 were inferred from genotype as being EMs and eight as PMs. A significant difference in temperament was observed between inferred CYP2D6 EM and PM individuals. CYP2D6 PMs had significantly lower harm avoidance scores (P = 0.003) than EMs. Furthermore, analysis of the harm avoidance sub‐scales revealed that the CYP2D6 PMs scored significantly lower on “fear of uncertainty” (P < 0.001), fatigability (P = 0.009), and shyness (P = 0.038) than EMs, but did not differ significantly from EMs on the worry/pessimism sub‐scale. No significant difference in character scores was detected between inferred CYP2D6 EMs and PMs. Our findings suggest that the CYP2D6 polymorphism may impact on personality, and one potential mechanism for this would be by influencing the generation of endogenous neurotransmitters in the brain. © 2004 Wiley‐Liss, Inc.
Expression of CCR7 in multiple sclerosis: Implications for CNS immunity
Authors: Kivisäkk Pia , Mahad Don J. , Callahan Melissa K. , Sikora Keith , Trebst Corinna , Tucky Barbara , Wujek Jerome , Ravid Rivka , Staugaitis Susan M. , Lassmann Hans , Ransohoff Richard M. 
Published: March 2004

AbstractIt is unclear how immune cells traffic between the lymphoid compartment and the central nervous system (CNS), which lacks lymphatic vessels and is shielded by the blood–brain barrier. We studied the expression of CCR7, a chemokine receptor required for migration of T cells and dendritic cells (DCs) to lymphoid organs, in the CNS of patients with multiple sclerosis (MS) to gain insight into pathways for CNS immune cell trafficking. Inflamed MS lesions contained numerous CCR7+ myeloid cells expressing major histocompatibility complex class II, CD68 and CD86, consistent with maturing DCs. CCR7+ DCs also were identified in cerebrospinal fluid (CSF). These observations suggested that the afferent limb of CNS immunity is comprised, in part, of DCs, which are generated within the CNS and migrate to deep cervical lymph nodes through the CSF after antigen capture. Ninety percent of CSF T cells expressed CCR7 and CSF from patients with MS was relatively depleted of CCR7‐negative effector‐memory T cells. In contrast, all T cells in parenchymal MS lesions lacked CCR7, indicating local retention and differentiation of central‐memory T cells upon restimulation by antigen within the CNS. These data suggested that the efferent limb of CNS immunity is executed by central‐memory T cells, which enter CSF directly from the circulation. Ann Neurol 2004
The urokinase receptor is overexpressed in the AIDs dementia complex and other neurological manifestations
Authors: Cinque Paola , Nebuloni Manuela , Santovito Maria Lisa , Price Richard W. , Gisslen Magnus , Hagberg Lars , Bestetti Arabella , Vago Gianluca , Lazzarin Adriano , Blasi Francesco , Sidenius Nicolai 
Published: March 2004

AbstractThe urokinase‐type plasminogen activator (uPA) and its receptor (uPAR) play an important role in extracellular matrix degradation and cell migration in the central nervous system (CNS). To investigate the role of the uPA/uPAR system in the pathophysiology of acquired immunodeficiency syndrome dementia complex (ADC), we measured soluble uPAR (suPAR) levels in cerebrospinal fluid (CSF) and plasma from human immunodeficiency virus (HIV)‐1–infected patients and controls. CSF suPAR levels were significantly higher in HIV‐1–infected patients than in controls and in patients with ADC or opportunistic CNS infections (CNS‐OIs) than in neurologically asymptomatic patients, irrespective of HIV‐1 disease stage. The highest levels of suPAR were found in patients with ADC, and among those with CNS‐OIs in patients with cytomegalovirus encephalitis or cryptococcosis. Plasma suPAR levels were higher in HIV‐1–infected patients than in controls and increased with HIV‐1 disease stage regardless of the presence of CNS disease. In patients with ADC or CNS‐OIs, CSF suPAR levels correlated with CSF HIV‐1 RNA, but not with plasma suPAR concentrations. Highly active antiretroviral therapy was associated with a significant and parallel decrease of both CSF suPAR and HIV‐1 RNA. In brain tissue from patients with HIV‐1 encephalitis, uPAR was highly expressed by microglial and multinucleated giant cells staining positively for HIV‐1. The overexpression of uPAR in the CNS of patients with ADC suggests that the uPA/uPAR system may contribute to the tissue injury and neuronal damage in this disease. Ann Neurol 2004
Desmin‐related myopathy with mallory body–like inclusions is caused by mutations of the selenoprotein N gene
Authors: Ferreiro Ana , Ceuterick‐de Groote Chantal , Marks Jared J. , Goemans Nathalie , Schreiber Gudrun , Hanefeld Folker , Fardeau Michel , Martin Jean‐Jacques , Goebel Hans H. , Richard Pascale , Guicheney Pascale , Bönnemann Carsten G. 
Published: March 2004

AbstractDesmin‐related myopathies (DRMs) are a heterogeneous group of muscle disorders, morphologically defined by intrasarcoplasmic aggregates of desmin. Mutations in the desmin and the α‐B crystallin genes account for approximately one third of the DRM cases. The genetic basis of the other forms remain unknown, including the early‐onset, recessive form with Mallory body–like inclusions (MB‐DRMs), first described in five related German patients. Recently, we identified the selenoprotein N gene (SEPN1) as responsible for SEPN‐related myopathy (SEPN‐RM), a unique early‐onset myopathy formerly divided in two different nosological categories: rigid spine muscular dystrophy and the severe form of classical multiminicore disease. The finding of Mallory body–like inclusions in two cases of genetically documented SEPN‐RM led us to suspect a relationship between MB‐DRM and SEPN1. In the original MB‐DRM German family, we demonstrated a linkage of the disease to the SEPN1 locus (1p36), and subsequently a homozygous SEPN1 deletion (del 92 nucleotide −19/+73) in the affected patients. A comparative reevaluation showed that MB‐DRM and SEPN‐RM share identical clinical features. Therefore, we propose that MB‐DRM should be categorized as SEPN‐RM. These findings substantiate the molecular heterogeneity of DRM, expand the morphological spectrum of SEPN‐RM, and implicate a necessary reassessment of the nosological boundaries in early‐onset myopathies. Ann Neurol 2004