bluuebunny/crossref_metadata_2025_split huggingface dataset:
Final Results of the 94–01 French Head and Neck Oncology and Radiotherapy Group Randomized Trial Comparing Radiotherapy Alone With Concomitant Radiochemotherapy in Advanced-Stage Oropharynx Carcinoma
Authors: Denis Fabrice , Garaud Pascal , Bardet Etienne , Alfonsi Marc , Sire Christian , Germain Thierry , Bergerot Philippe , Rhein Beatrix , Tortochaux Jacques , Calais Gilles 
Published: December 2003

Purpose We report the 5-year survival and late toxicity results of a randomized clinical trial, which showed a 3-year improvement in overall survival and locoregional control of stage III or IV oropharynx carcinoma, using concomitant radiochemotherapy (arm B), compared with standard radiotherapy (arm A). Patients and Methods A total of 226 patients were entered onto a phase III multicenter randomized trial comparing radiotherapy alone (70 Gy in 35 fractions; arm A) with concomitant radiochemotherapy (70 Gy in 35 fractions with three cycles of a 4-day regimen comprising carboplatin and fluorouracil; arm B). Prognostic factors were evaluated by univariate and multivariate analysis. Five-year late toxicity was evaluated using National Cancer Institute Common Toxicity Criteria for neurological toxicity, hearing, taste, mandibula, and teeth damage, and Radiation Therapy Oncology Group toxicity criteria for skin, salivary gland, and mucosa. Results Five-year overall survival, specific disease-free survival, and locoregional control rates were 22% and 16% (log-rank P = .05), 27% and 15% (P = .01), and 48% and 25% (P = .002), in arm B and arm A, respectively. Stage IV, hemoglobin level lower than 125 g/L, and standard treatment were independent prognostic factors of short survival and locoregional failure by univariate and multivariate analysis. One or more grade 3 to 4 complications occurred in 56% of the patients in arm B, compared with 30% in arm A (P was not significant). Conclusion Concomitant radiochemotherapy improved overall survival and locoregional control rates and does not statistically increase severe late morbidity. Anemia was the most important prognostic factor for survival in both arms.
Diurnal Variation in Rat Liver Thyroid Hormone Receptor (TR)-α Messenger Ribonucleic Acid (mRNA) Is Dependent on the Biological Clock in the Suprachiasmatic Nucleus, whereas Diurnal Variation of TRβ1 mRNA Is Modified by Food Intake
Authors: Doulabi B. Zandieh , Schiphorst M. Platvoet-Ter , Kalsbeek A. , Fliers E. , Bakker O. , Wiersinga W. M. 
Published: December 2003

Abstract
Previous studies have shown a diurnal variation of certain isoforms of thyroid hormone receptors (TR) in rat liver. The genesis of these diurnal changes is still unknown. To clarify whether the biological clock, located in the hypothalamic suprachiasmatic nucleus (SCN), is involved, we made selective SCN lesions. Rats with an SCN lesion lost their circadian rhythm of plasma corticosterone and TSH when compared with intact animals. TRα1 and TRα2 mRNA expression of control rats was higher in the light period than in the dark period; changes that were abolished in the rats with SCN lesions. In contrast, liver TRβ1 mRNA of intact rats showed a diurnal variation that failed to reach statistical significance. To evaluate whether these effects could be explained indirectly by the disappearance of rhythmic feeding behavior in rats with SCN lesions, we performed a second experiment in which otherwise intact animals were subjected to a regular feeding (RF) schedule, with one meal every 4 h. When compared with rats with free access to food, RF only affected TRβ1 mRNA expression and had no effect on the diurnal changes in TRα1 and TRα2. We conclude that liver TRβ1 expression is most clearly affected by food intake. Diurnal changes in liver TRα1 and TRα2 are controlled by the biological clock in the SCN but not via changes in the daily rhythm of food intake. The findings may have physiological relevance for diurnal variation of T3-dependent gene expression, which is supported by a diurnal variation in the expression of the 5′-deiodinase gene.
Microbial Degradation of Tar Oil Compounds under Different Redox Conditions
Authors: Mundt Matthias , Althoff Katrin , Dott Wolfgang , Hollender Juliane 
Published: December 2003

AbstractThe microbial transformation of typical tar oil compounds such as acridine, benzo(b)thiophene, dibenzofuran, indane, and indene under different redox conditions was investigated in microcosm studies. Under aerobic conditions the inherent contamination in polluted soil as well as the added N‐, S‐, O‐ heterocyclic and homocyclic compounds were transformed predominantly apart from thiophene. 1‐Indanone was detected by RP‐HPLC‐DAD and GC‐MS as an intermediate metabolite from indane and indene. Under nitrate and sulfate reducing conditions indane, benzo(b)thiophene, and dibenzofuran were transformed in assays with the polluted soil samples from well B 65 and B 66 within 426 days, whereas they were persistent in assays with the highly polluted soil B 67. All heterocyclic and homocyclic compounds added to the non‐contaminated soil from well B 85 were not degraded under nitrate and sulfate reducing conditions, too. The results indicate that for the decision, wether natural attenuation can be implemented in the remediation of contaminated site, in addition to BTEX and PAHs especially the fate of further tar oil compounds in anoxic aquifers has to be considered.
A severe autosomal‐dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: An unusual familial Mediterranean fever phenotype or another MEFV‐associated periodic inflammatory disorder?
Authors: Aldea Anna , Campistol Josep M. , Arostegui Juan I. , Rius Josefa , Maso Montserrat , Vives Jordi , Yagüe Jordi 
Published: December 2003

AbstractFamilial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring short attacks of fever and serositis. Secondary AA amyloidosis is the worst complication of the disease and often determines the prognosis. The MEFV gene, on chromosome 16p13.3, is responsible for the disease and around 30 mutations have been reported to date. Colchicine is the standard FMF treatment today, and prevents both attacks and amyloid deposition in 95% of patients. Here we describe a three‐generation Spanish kindred with five family members affected by a severe periodic inflammatory disorder associated with renal AA amyloidosis and colchicine unresponsiveness. Clinical diagnosis of definite FMF disease was made based on the Tel‐Hashomer criteria set. Genetic analyses revealed that all subjects were heterozygous for the new H478Y MEFV variant, segregating with the disease. In addition, mutations in the TNFRSF1A and CIAS1/PYPAF1/NALP3 genes, related to the dominantly inherited autoinflammatory periodic syndromes, were ruled out. However, the dominant inheritance of the disease, the long fever episodes with a predominant joint involvement, and the resistance to colchicine in these patients raise the question of whether the periodic syndrome seen in this kindred is a true FMF disease with unusual manifestations or rather another MEFV‐associated periodic syndrome. We conclude that the new H478Y MEFV mutation is the dominant pathological variant causing the inflammatory periodic syndrome in this kindred and that full‐length analyses of the MEFV gene are needed to obtain an adequate diagnosis of patients with clinical suspicion of a hereditary periodic fever syndrome, especially those from non‐ancestral populations. © 2003 Wiley‐Liss, Inc.
DEB test for Fanconi anemia detection in patients with atypical phenotypes
Authors: Esmer Carmen , Sánchez Silvia , Ramos Sandra , Molina Bertha , Frias Sara , Carnevale Alessandra 
Published: December 2003

AbstractPancytopenia, hyperpigmentation, small stature, congenital abnormalities, and predisposition to neoplasia characterize Fanconi anemia (FA). The clinical phenotype is extremely variable, therefore the diagnosis is frequently delayed until the pancytopenia appears, making diagnosis difficult on the basis of clinical manifestations alone. Hypersensitivity of FA cells to the clastogenic effect of diepoxybutane (DEB) provides a unique marker for the diagnosis before the beginning of hematological manifestations. Our aim in this study was to detect FA in children with atypical manifestations to define which conditions should be routinely included in the DEB test screening. We performed the chromosomal breakage test in 34 patients with probable FA and 83 patients with clinical conditions that could suggest FA, but are not usually screened by the DEB test: 20 patients with aplastic anemia, 20 patients with VACTERL association, 20 with radial ray abnormalities, 7 with tracheo‐esophageal fistulae, 12 with anal atresia, and 4 with myelodysplastic syndrome. We found 18 DEB‐positive patients: 12 were in the group of probable FA and 6 in the other groups. Among the last ones: three were included because of aplastic anemia, without any other sign of FA, however when re‐examined, other anomalies were detected. The third patient had anal atresia, renal hypoplasia, pre‐axial polydactyly, and normal blood cell counts and was diagnosed as having VACTERL association. The other two patients lacking physical or hematological signs were identified among the group of radial ray abnormalities. Thus, our results highlight the need to increase the number of abnormalities indicating need for a DEB test. Delay in the diagnosis of FA may have serious consequences for the patients and their family members. © 2003 Wiley‐Liss, Inc.
Different phenotypic expression in monozygotic twins with Huntington disease
Authors: Anca M.H. , Gazit E. , Loewenthal R. , Ostrovsky O. , Frydman M. , Giladi N. 
Published: December 2003

AbstractMonozygotic (MZ), 46‐year‐old, male twins, carrying the same Huntington disease (HD) mutation, presented with a different clinical course. In one of the twins, the disease process started at the age of 32 years with chorea, dysarthria, and a depressed mood. Over 14 years, the disease progressed to total functional dependence. The second twin presented at age 35 with gait disturbances. His behavior became aggressive with an obsessive pattern, whereas the motor features included hypokinesia, rigidity, gait unsteadiness, and dysarthria. This is the first report of genetic identity associated with different age of disease onset as well as a different motor and behavioral phenotype. Postzygotic events are a likely explanation for the observed differences of phenotype in these genetically identical twins. © 2003 Wiley‐Liss, Inc.
A genomic scan for habitual smoking in families of alcoholics: Common and specific genetic factors in substance dependence
Authors: Bierut Laura Jean , Rice John P. , Goate Alison , Hinrichs Anthony L. , Saccone Nancy L. , Foroud Tatiana , Edenberg Howard J. , Cloninger C. Robert , Begleiter Henri , Conneally P. Michael , Crowe Raymond R. , Hesselbrock Victor , Li Ting‐Kai , Nurnberger John I. , Porjesz Bernice , Schuckit Marc A. , Reich Theodore 
Published: December 2003

AbstractSmoking is a highly heritable, addictive disorder that commonly co‐occurs with alcohol dependence. The purpose of this study is to perform a genomic screen for habitual smoking and comorbid habitual smoking and alcohol dependence in families from the Collaborative Study on the Genetics of Alcoholism (COGA). Subjects were assessed using the Semi‐Structured Assessment for the Genetics of Alcoholism (SSAGA) to evaluate alcohol dependence and habitual smoking (smoking one pack per day or more for at least 6 months). Sixty seven multi‐generational families with 154 independent sibling pairs affected with habitual smoking were genotyped in a screening sample. Analyses on 79 multi‐generational families with 173 independent sibling pairs were repeated in a replication sample. Sibpair analyses were performed using ASPEX. Four chromosomal regions in the screening sample had increased allele sharing among sibling pairs for habitual smoking with a LOD score greater than 1 (chromosomes 5, 9, 11, and 21). The highest LOD score was on chromosome 9 (LOD = 2.02; allele sharing 58.9%). Four chromosomal regions also had modest evidence for linkage to the comorbid phenotype habitual smoking and alcohol dependence (chromosomes 1, 2, 11, 15); and the strongest finding was on chromosome 2 (LOD = 3.30; allele sharing 69.1%). Previously identified areas (chromosomes 1 and 7) implicated in the development of alcohol dependence in this same data set did not provide evidence for linkage to habitual smoking in the screening sample. In the replication data set, there continued to be increased allele sharing near peaks identified in the screening sample on chromosomes 2 and 9, but the results were modest. An area on chromosome 7, approximately 60 cM from a location previously identified in linkage analysis with alcohol dependence, had increased allele sharing for the comorbid habitual smoking and alcohol dependence. These data provide evidence of specific genetic regions involved in the development of habitual smoking and not alcohol dependence. Conversely, genetic regions that influence the development of alcohol dependence do not appear to contribute to the development of habitual smoking. Finally, there is also evidence of an area on chromosome 2 that may reflect a common genetic vulnerability locus to both habitual smoking and alcohol dependence. © 2003 Wiley‐Liss, Inc.
Molecular cytogenetic analysis of complex chromosomal rearrangements in patients with mental retardation and congenital malformations: Delineation of 7q21.11 breakpoints
Authors: Vermeulen Stefan , Menten Björn , Van Roy Nadine , Van Limbergen Heidi , De Paepe Anne , Mortier Geert , Speleman Frank 
Published: December 2003

AbstractConstitutional de novo complex chromosomal rearrangements (CCRs) are a rare finding in patients with mild to severe mental retardation. CCRs pose a challenge to the clinical cytogeneticist: generally CCRs are assumed to be the cause of the observed phenotypic abnormalities, but the complex nature of these chromosomal changes often hamper the accurate delineation of the chromosomal breakpoints and the identification of possible imbalances. In a first step towards a more detailed molecular cytogenetic characterization of CCRs, we studied four de novo CCRs using multicolor fluorescent in situ hybridization (M‐FISH), comparative genomic hybridization (CGH), and FISH with region specific probes. These methods allowed a more refined characterization of the breakpoints in three of the four CCRs. The occurrence of 7q breakpoints in three out of these four CCRs and in 30% of reported CCRs suggested preferential involvement of this chromosomal region in the formation of CCRs. Further analysis of these 7q breakpoints revealed a 2 Mb deletion at 7q21.11 in one patient and involvement of the same region in a cryptic insertion in a second patient. This particular region contains at least 5 candidate genes for mental retardation. The other patient had a breakpoint more proximal to this region. The present data together with these from the literature provide evidence that a region within 7q21.11 may be prone to breakage and formation of CCRs. © 2003 Wiley‐Liss, Inc.
Brothers with Chudley–McCullough syndrome: Sensorineural deafness, agenesis of the corpus callosum, and other structural brain abnormalities
Authors: Østergaard Elsebet , Faurholt Pedersen Vibeke , Skriver Elisabeth B. , Brøndum‐Nielsen Karen 
Published: December 2003

AbstractWe describe two brothers with Chudley–McCullough syndrome who are 5 and 17 years old. They were born to healthy consanguineous parents of Pakistani descent. They had severe sensorineural deafness and neuroimaging showed corpus callosum agenesis and other structural brain abnormalities. The Chudley–McCullough syndrome is an autosomal recessive disorder, first described by Chudley et al. [1997: Am J Med Genet 68:350–356]. The original description of the syndrome includes hydrocephalus due to obstruction of the foramen of Monro and early‐onset severe to profound sensorineural deafness. We review the findings in the two patients we describe, four children reported in the literature and two patients reported by Hendriks et al. [1999: Am J Med Genet 86:183–186] with sensorineural deafness, corpus callosum agenesis, and interhemispheric cysts, who may well have Chudley–McCullough syndrome. All patients had sensorineural deafness. The neuroimagings of all eight patients showed colpocephaly, which is most likely caused by corpus callosum agenesis. Three patients had other structural brain abnormalities: cortical dysplasia and gray matter heterotopia. We suggest a revision of the clinical description since the most likely basic developmental defect is corpus callosum agenesis and not foramen of Monro obstruction. © 2003 Wiley‐Liss, Inc.
Genetic variants in ZIC1, ZIC2, and ZIC3 are not major risk factors for neural tube defects in humans
Authors: Klootwijk Riko , Groenen Pascal , Schijvenaars Mascha , Hol Frans , Hamel Ben , Straatman Huub , Steegers‐Theunissen Régine , Mariman Edwin , Franke Barbara 
Published: December 2003

AbstractNeural tube defects (NTD) are congenital malformations arising from incomplete neural tube closure during early embryogenesis. Most NTD in humans show complex inheritance patterns, with both genetic and environmental factors involved in the etiology of this malformation. More than 120 mouse models for human NTD exist. NTD have been observed in mice deficient for the Zic family genes, Zic1, Zic2, and Zic3. We performed mutation analysis in the human orthologs of these genes using DNA material from a large panel of NTD patients. In ZIC2 we identified a deletion of one codon that encodes an alanine residue located in the amino terminal alanine stretch of the protein. The deletion was present in one patient, but not in 364 controls. That may suggest a role—albeit small—of this variant in the etiology of NTD in humans. Transmission disequilibrium testing of a frequent polymorphism in the ZIC2 gene (1059C > T, H353H) in parent‐spina bifida aperta child triads showed no association with NTD. One silent polymorphism (858G > A, V286V) of unknown significance was identified in ZIC3. Neither mutations nor polymorphisms were found in the coding region or flanking sequences of ZIC1. Our data indicate that ZIC1, ZIC2, and ZIC3 are not major risk factors for NTD in humans. © 2003 Wiley‐Liss, Inc.
Metaphyseal chondrodysplasia with cone‐shaped epiphyses: A specific form involving the lower limbs
Authors: Dieux‐Coëslier Anne , Moerman Alexandre , Holder Muriel , Boute Odile , Maroteaux Pierre , Manouvrier Sylvie , Le Merrer Martine 
Published: December 2003

AbstractThree unrelated patients affected by a characteristic metaphyseal chondrodysplasia with cup‐shaped metaphyses of the knees are described. Lower femoral and upper tibial cone‐shaped epiphyses were embedded in the metaphyses. Main clinical features are short stature, shortening of the lower limbs, limitation of knee extension, and normal hands length. Radiographs of skull, spine, and hands showed no abnormality. This particular appearance of the knees has been seldom described in acquired disease such as repeated injuries, meningoccocemia, scurvy, and hypervitaminosis A. Metaphyseal dysplasias with these distinctive radiological findings of the knees are uncommon. Differential diagnosis includes trichoscyphodysplasia and acroscyphodysplasia among others. Two other cases reported by Kozlowski showed the most similarities to our three cases and defined a new form of metaphyseal dysplasia with specific lower limbs involvement and cup‐shaped metaphyses. © 2003 Wiley‐Liss, Inc.
Novel CACNA1A mutation causes febrile episodic ataxia with interictal cerebellar deficits
Authors: Subramony S. H. , Schott Kelly , Raike Robert S. , Callahan Joel , Langford Leigh R. , Christova Peka S. , Anderson John H. , Gomez Christopher M. 
Published: December 2003

AbstractEpisodic ataxia type 2 (EA2) is a dominantly inherited disorder, characterized by spells of ataxia, dysarthria, vertigo, and migraines, associated with mutations in the neuronal calcium‐channel gene CACNA1A. Ataxic spells lasting minutes to hours are provoked by stress, exercise, or alcohol. Some patients exhibit nystagmus between spells and some develop progressive ataxia later in life. At least 21 distinct CACNA1A mutations have been identified in EA2. The clinical and genetic complexities of EA2 have offered few insights into the underlying pathogenic mechanisms for this disorder. We identified a novel EA2 kindred in which members had ataxic spells induced by fevers or high environmental temperature. We identified a novel CACNA1A mutation (nucleotides 1253+1 G→A) that was present in all subjects with febrile spells or ataxia. Moreover, we found that, regardless of age or interictal clinical status, all affected subjects had objective evidence of abnormal saccades, ocular fixation, and postural stability. These findings suggest that early cerebellar dysfunction in EA2 results from the intrinsically abnormal properties of the CACNA1A channel rather than a degenerative process.
Hereditary spastic paraparesis: Disrupted intracellular transport associated with spastin mutation
Authors: McDermott Christopher J. , Grierson Andrew J. , Wood Jonathan D. , Bingley Megan , Wharton Stephen B. , Bushby Katharine M. D. , Shaw Pamela J. 
Published: December 2003

AbstractThe commonest cause of hereditary spastic paraplegia (HSP) is mutation in the spastin gene. Both the normal function of spastin in the central nervous system and the mechanism by which mutation in spastin causes axonal degeneration are unknown. One hypothesis is that mutant spastin disrupts microtubule dynamics, causing an impairment of organelle transport on the microtubule network, which leads to degeneration in the distal parts of long axons. To study this neuronal and non‐neuronal cells were transfected with either wild type or mutant spastin proteins. We demonstrated evidence of a transient interaction of wild‐type spastin with microtubules, with resulting disassembly of microtubules, supporting a role for wild‐type spastin as a microtubule‐severing protein. Mutant spastin demonstrated an abnormal interaction with microtubules, colocalizing with but no longer severing microtubules. The abnormal interaction of mutant spastin with microtubules was demonstrated to be associated with an abnormal perinuclear clustering of mitochondria and peroxisomes, suggestive of an impairment of kinesin‐mediated intracellular transport. Our findings indicate that an abnormal interaction of mutant spastin with microtubules, which disrupts organelle transport on the microtubule cytoskeleton, is likely to be the primary disease mechanism in HSP caused by missense mutations in the spastin gene.
Pathogenesis of clinical signs in recessive ataxia with saccadic intrusions
Authors: Swartz Barbara E. , Li Sheng , Bespalova Irina , Burmeister Margit , Dulaney Eugene , Robinson Farrel R. , Leigh R. John 
Published: December 2003

AbstractWe describe a family of Slovenian descent with progressive ataxia, corticospinal signs, axonal sensorimotor neuropathy, and disruption of visual fixation by saccadic intrusions. Chromosome mapping indicated a mutation on 1p36, and this recessive disorder has been designated spinocerebellar ataxia with saccadic intrusions. Affected patients showed overshooting horizontal saccades, macrosaccadic oscillations, and increased velocity of larger saccades; other eye movements were normal. Slowed conduction in axons that are selectively vulnerable to the molecular defect could explain both the sensorimotor neuropathy and the saccadic disorder, which would be caused by delayed feedback control because of slow conduction in cerebellar parallel fibers.Supplementary material to this article can be viewed online at www.interscience.wiley.com/jpages/0364‐5134/suppmat/54_6.