bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solitary median maxillary central incisor syndrome: Clinical case with a novel mutation of sonic hedgehog
Authors: Garavelli Livia , Zanacca C. , Caselli G. , Banchini G. , Dubourg C. , David V. , Odent S. , Gurrieri F. , Neri G. 
Published: April 2004

AbstractSolitary median maxillary central incisor (SMMCI) is a rare dental anomaly. It is usually considered as a minor manifestation of holoprosencephaly (HPE). Some reported families had severe cases of HPE in some members and SMMCI in others. Mutations of Sonic Hedgehog (SHH) have been documented in these families. SMMCI has also been found as an isolated finding or together with other anomalies such as microcephaly, short stature, endocrine pathology, and choanal atresia. We describe a patient with SMMCI and a novel SHH mutation: Val332Ala. © 2003 Wiley‐Liss, Inc.
A female with complete lack of Müllerian fusion, postaxial polydactyly, and tetralogy of fallot: Genetic heterogeneity of McKusick–Kaufman syndrome or a unique syndrome?
Authors: Slavotinek Anne M. , Dutra Amalia , Kpodzo Dzifa , Pak Evgenia , Nakane Takaya , Turner Joyce , Whiteford Margo , Biesecker Leslie G. , Stratton Pamela 
Published: April 2004

AbstractWe report a 19‐year‐old, non‐Amish Caucasian female patient with primary amenorrhea caused by complete lack of Müllerian fusion with vaginal agenesis or Müllerian aplasia (MA), postaxial polydactyly (PAP), and tetralogy of Fallot. The genital tract anomaly of MA with and without renal or skeletal anomalies comprises Mayer–Rokitansky–Kuster–Hauser syndrome, which has not been reported with tetralogy of Fallot. The phenotypic triad of anomalies most closely resembled McKusick–Kaufman syndrome (MKS; OMIM 236700), a rare multiple congenital anomaly syndrome comprised of hydrometrocolpos (HMC), PAP, and congenital heart malformation that is inherited in an autosomal recessive pattern. While upper reproductive tract anomalies have not been reported with MKS, they have been reported with Bardet–Biedl syndrome (BBS), a syndrome that significantly overlaps with MKS. Both MKS and BBS can be caused by mutations in the MKKS or BBS6 gene on chromosome 20p12 and BBS is also associated with mutations in other genes (BBS1, BBS2, BBS4, and BBS7). To address this heterogenity, we sequenced the causative genes in MKS and BBS but no mutations in these five genes were identified. Fluorescence in situ hybridization (FISH) excluded large deletions of chromosome 20p12 and microsatellite marker studies confirmed biparental inheritance for all of the known BBS loci. The dual midline fusion defects of tetralogy of Fallot and MA suggests that either this patient has a unique syndrome with a distinct genetic etiology or that she has a genetically heterogeneous or variant form of MKS. Published 2004 Wiley‐Liss, Inc.
Polymorphism of 5HT2A serotonin receptor gene is implicated in smoking addiction
Authors: do Prado‐Lima P.A.S. , Chatkin J.M. , Taufer M. , Oliveira G. , Silveira E. , Neto C.A. , Haggstram F. , Bodanese L.C. , da Cruz I.B.M. 
Published: April 2004

AbstractSmoking behavior is influenced by genetic factors. Polymorphisms affecting the dopaminergic system have been linked to smoking habits. The aim of this study was to investigate if the T102C polymorphism of the 5‐HT2A receptor gene is related to tobacco use, since this receptor modulates the mesolimbic dopamine system and the C allele is associated with reduced receptor gene expression. A sample of 625 subjects were genotyped and classified according to their smoking behavior (never, former, or current smokers). We found differences in the distribution of the genotypes when the current smokers were compared with the never + former smokers, suggesting that T102C polymorphism is associated with maintenance, but not with initiation of the smoking habit. The CC genotype was more frequent in the current smokers than in the never + former smokers (χ2 = 6.825, P = 0.03). The odds ratio of being a current smoker with a CC genotype was 1.63, 95% CI 1.06–2.51. © 2004 Wiley‐Liss, Inc.
CAG nucleotide repeat profiles in persons with schizophrenia or schizoaffective disorders with and without tardive dyskinesia: Pilot study
Authors: Lowrimore Patricia , Mulvihill David , Epstein Andrew , McCormack Michael , Wang Yuh‐Hwa 
Published: April 2004

AbstractTardive dyskinesia (TD) is a drug‐induced syndrome of involuntary movements often associated with neuroleptic treatment of psychiatric conditions. Huntington's disease (HD) and other neurological conditions are caused by CAG nucleotide repeat expansions in specific genes. We, therefore, explore the hypothesis that TD may be related to CAG repeat expansion by using the repeat expansion detection (RED) method as a measure of CAG content without knowledge of the location of the responsible gene. The number of CAG repeats ([CAG]n) from persons with schizophrenia or schizoaffective disorders with (n = 10) and without (n = 9) TD are determined. A comparison of [CAG]n in persons with (56.90 ± 23.45 repeats) and without (57.00 ± 19.35 repeats) TD was not statistically different. The total [CAG]n was determined by combining [CAG]n for both groups. The median of 45 repeats was used to divide the total into two groups (SG1 and SG2 with smaller and larger [CAG]n fragments, respectively) and a means analysis of the two subgroups based on [CAG]n demonstrated that SG1 (n = 10 samples at 45 repeats per sample, mean [CAG]n = 45.00 ± 0.00) was significantly smaller than SG2 (n = 9, ranging from 48 to 120 repeats, mean = 70.22 ± 24.83; P < 0.005). Thus, this lends support to the idea of CAG repeat expansions in the study population. Results are encouraging that a larger population and a more structured subject selection process may yield more meaningful information about the relationship between CAG repeat expansion and TD. © 2004 Wiley‐Liss, Inc.
Childhood‐onset schizophrenia and tryptophan hydroxylase gene polymorphism
Authors: Sekizawa Takahiro , Iwata Yasuhide , Nakamura Kazuhiko , Matsumoto Hideo , Suzuki Atsuko , Suzuki Katsuaki , Sekine Yoshimoto , Takei Noriyoshi , Minabe Yoshio , Mori Norio 
Published: April 2004

AbstractWe explored the relationship between the tryptophan hydroxylase gene polymorphism and susceptibility to childhood‐onset schizophrenia in a Japanese sample. Subjects were 51 Japanese patients who met DSM‐IV criteria for schizophrenia before age 16 and 148 Japanese healthy controls. DNA was extracted from whole blood and genotyping was performed by PCR‐RFLP using Nhe I. The frequency of the A allele was relatively higher in patients with childhood‐onset schizophrenia than in controls (odds ratio, OR = 1.47, 95% CI = 0.97–2.37, P = 0.097). There was a nearly doubling of the risk for childhood‐onset schizophrenia associated with the AA genotype compared to other genotype groups; OR = 1.97, 95% CI = 0.91–4.22, P = 0.058. © 2004 Wiley‐Liss, Inc.
Statistical confirmation of negative results of association studies in genetic epidemiology
Authors: Wellek S. , Schumann G. 
Published: April 2004

AbstractOne of the most important reasons warranting the common reservation about publishing association studies with negative results is due to the fundamental fact that an insignificant result of a statistical testing procedure tailored for establishing an association, fails to provide conclusive evidence of the contrary. In this contribution, we show how the methodology of equivalence testing, as provided by modern biostatistics, can be exploited for removing this basic flaw. In order to keep the exposition as simple as possible, we restrict discussion to the setting of a study which aims at ruling out that some given single SNP has a relevant impact on the risk of developing the disease under consideration. As solutions to the problem of how to perform a valid confirmatory analysis of a trial of this type, two different approaches are presented: (i) exact Fisher type test for equivalence of an odds ratio to unity; (ii) distribution‐free test for equivalence of cases and controls with respect to the full (i.e., trinomial) genotype distributions. The practical implementation of both testing procedures are described in detail and illustrated with examples taken from recent studies of the genetic epidemiology of psychiatric disorders. © 2004 Wiley‐Liss, Inc.
Identification of families with cortical Lewy body disease
Authors: Harding Antony J. , Das Anurina , Kril Jillian J. , Brooks William S. , Duffy David , Halliday Glenda M. 
Published: April 2004

AbstractUntil recently, cortical Lewy body disease (CLB) was considered essentially the same as dementia with Lewy bodies (DLB). It is now known patients with Parkinson's disease (PD) with a later‐onset dementia (PD‐dementia) have the same pattern and extent of cortical Lewy body pathology. Inheritance patterns of CLB have not been evaluated previously. To identify genetic influence on CLB, all cases with this pathology need to be considered. We selected 180 cases meeting clinical and/or pathological criteria for DLB or PD (±dementia) from two patient groups: a PD and PD‐dementia brain donor program, and a case‐control study of Alzheimer's disease (AD). Cases meeting NINCDS‐ADRDA criteria for probable AD were excluded and non‐demented PD cases used as a comparison group. A detailed family history was taken analyzing onset and progression of dementia and PD phenotypes and a family tree constructed. The frequency of a positive family history of dementia and/or PD and risk of developing CLB in relatives was calculated. Fifty‐five percent of dementia and 52% of PD cohorts did not have relatives with clinical disease. There was no increased frequency of familial disease in the CLB cohort compared with PD. However, in half the CLB families, rather than a dominant dementia, the clinical presentation varied (dementia and/or PD). Unlike PD, there was an increased risk of dementia if CLB was present in a parent (∼20% risk) compared with another family member (∼5% risk), suggesting CLB is more likely than PD to occur in a pattern consistent with autosomal dominant inheritance. © 2004 Wiley‐Liss, Inc.
Association of the dopamine D5 receptor with attention deficit hyperactivity disorder (ADHD) and scores on a continuous performance test (TOVA)
Authors: Manor Iris , Corbex Marylis , Eisenberg Jacques , Gritsenkso Inga , Bachner‐Melman Rachel , Tyano Samuel , Ebstein Richard P. 
Published: April 2004

AbstractTowards further clarifying the role of dopamine D5 receptor (DRD5) microsatellite polymorphism in the etiology of ADHD, we used a robust family based strategy to test for association between DRD5 and this disorder. Additionally, a neuropsychological mechanism by which this allele may confer risk was explored by examining the relationship between DRD5 genotype and scores on a continuous performance test. DNA was obtained from 164 probands and their parents. Additionally, the majority of these probands were administered a computerized continuous performance test, the Test Of Variables of Attention (TOVA). We first confirmed preferential transmission (TDT χ2 = 7.02, P = 0.008) of the 148 base pair allele in 155 informative transmissions (94 transmitted and 61 non‐transmitted 148 bp allele). Additionally, we used a family‐based association test (FBAT) and observed significant multivariate association using FBAT between TOVA scores before methylphenidate administration and the DRD5 microsatellite polymorphism across all four TOVA variables: multi‐allelic, multivariate test χ2 = 16.32, P = 0.037 when the 148 bp allele was compared to all others (collapsed genotype) that was also significant (χ2 = 59.20, P = 0.025) when all 14 alleles (full genotype) were analyzed. Following methylphenidate, no significant association was observed (χ2 = 12.08, P = 0.147 for 148 bp versus all others) and, similarly, for all 14 alleles (χ2 = 47.18, P = 0.343). In summary, the main finding of this report is that the DRD5 repeat polymorphism confers a small but significant risk for ADHD consistent with previous reports. Provisional results in this single investigation suggest that the DRD5 microsatellite also affects performance scores on the TOVA. © 2004 Wiley‐Liss, Inc.
Vascular endothelial growth factor mediates vasogenic edema in acute lead encephalopathy
Authors: Hossain Mir Ahamed , Russell Juliet C. , Miknyoczki Sheila , Ruggeri Bruce , Lal Bachchu , Laterra John 
Published: April 2004

AbstractBrain injury from inorganic Pb2+ is considered the most important environmental childhood health hazard worldwide. The microvasculature of the developing brain is uniquely susceptible to high level Pb2+ toxicity (ie, Pb2+ encephalopathy) characterized by cerebellar hemorrhage, increased blood–brain barrier permeability, and vasogenic edema. However, the specific molecular mediators of Pb2+ encephalopathy have been elusive. We found that Pb2+ induces vascular endothelial growth factor/vascular permeability factor (VEGF) in cultured astrocytes (J Biol Chem, 2000;275:27874–27882). The study presented here asks if VEGF dysregulation contributes mechanistically to Pb2+ encephalopathy. Neonatal rats exposed to 4% Pb‐carbonate develop the histopathological features of Pb2+ encephalopathy seen in children. Cerebellar VEGF expression increased approximately twofold (p < 0.01) concurrent with the development of cerebellar microvascular hemorrhage, enhanced vascular permeability to serum albumin, and vasogenic cerebellar edema (p < 0.01). No change in VEGF expression occurred in cerebral cortex that does not develop these histopathological complications of acute Pb2+ intoxication. Pb2+ exposure increased phosphorylation of cerebellar Flk‐1 VEGF receptors and the Flk‐1 inhibitor CEP‐3967 completely blocked cerebellar edema formation without affecting microhemorrhage formation or blood–brain barrier permeability. This establishes that Pb2+‐induced vasogenic edema formation develops via a Flk‐1–dependent mechanism and suggests that the vascular permeability caused by Pb2+ is Flk‐1 independent.
Agostische Wechselwirkungen in d0‐Alkylmetallkomplexen
Authors: Scherer Wolfgang , McGrady G. Sean 
Published: April 2004

AbstractDas Phänomen und die Ursachen der agostischen Wechselwirkung werden hier vorgestellt und neu beschrieben. An einen historischen Rückblick schließt sich eine Übersicht der experimentellen Methoden an, die zur Untersuchung von agostischem Verhalten genutzt werden. Anhand einer Reihe einfacher Alkylmetallkomplexe wird ein neues Modell für die agostische Wechselwirkung in d0‐Systemen vorgestellt. Dabei wird sich eine klare Abgrenzung dieser Systeme von agostischen Komplexen später Übergangsmetalle ergeben. Entgegen den bisherigen Annahmen zeigt sich, dass Faktoren wie die Zahl der Valenzelektronen und die Koordinationszahlen nicht notwendigerweise eine wesentliche Rolle bei der Ausbildung einer agostischen Wechselwirkung in d0‐Systemen spielen. Mit der “Atoms in Molecules”‐Theorie wird die Ladungsdichteverteilung in mehreren Alkylübergangsmetallkomplexen sowohl experimentell als auch theoretisch untersucht. Demnach ist die lokale Ladungskonzentration eine entscheidende Größe bei agostischen Wechselwirkungen. Schließlich werden wir erstmals eine Möglichkeit aufzeigen, wie die Größe und die Verteilung von Ladungskonzentrationen gezielt manipuliert und somit die Stärke der agostischen Wechselwirkung in d0‐Alkylmetallkomplexen verändert werden kann.
Inhibition of the Trichoderma reesei cellulases by cellobiose is strongly dependent on the nature of the substrate
Authors: Gruno Marju , Väljamäe Priit , Pettersson Göran , Johansson Gunnar 
Published: April 2004

AbstractThe inhibition effect of cellobiose on the initial stage of hydrolysis when cellobiohydrolase Cel 7A and endoglucanases Cel 7B, Cel 5A, and Cel 12A from Trichoderma reesei were acting on bacterial cellulose and amorphous cellulose that were [3H]‐ labeled at the reducing end was quantified. The apparent competitive inhibition constant (Ki) for Cel 7A on [3H]‐bacterial cellulose was found to be 1.6 ± 0.5 mM, 100‐fold higher than that for Cel 7A acting on low‐molecular‐weight model substrates. The hydrolysis of [3H]‐amorphous cellulose by endoglucanases was even less affected by cellobiose inhibition with apparent Ki values of 11 ± 3 mM and 34 ± 6 mM for Cel 7B and Cel 5A, respectively. Contrary to the case for the other enzymes studied, the release of radioactive label by Cel 12A was stimulated by cellobiose, possibly due to a more pronounced transglycosylating activity. Theoretical analysis of the inhibition of Cel 7A by cellobiose predicted an inhibition analogous to that of mixed type with two limiting cases, competitive inhibition if the prevalent enzyme‐substrate complex without inhibitor is productive and conventional mixed type when the prevalent enzyme‐substrate complex is nonproductive. © 2004 Wiley Periodicals, Inc.
Long‐term continuous monitoring of dissolved oxygen in cell culture medium for perfused bioreactors using optical oxygen sensors
Authors: Gao Frank G. , Jeevarajan Antony S. , Anderson Melody M. 
Published: April 2004

AbstractFor long‐term growth of mammalian cells in perfused bioreactors, it is essential to monitor the concentration of dissolved oxygen (DO) present in the culture medium to ascertain the health of the cells. An optical oxygen sensor based on dynamic fluorescent quenching was developed for long‐term continuous measurement of DO for NASA‐designed rotating perfused bioreactors. Tris(4,7‐diphenyl‐1,10‐phenanthroline) ruthenium(II) chloride is employed as the fluorescent dye indicator. A pulsed, blue LED was chosen as the excitation light source. The sensor can be sterilized using an autoclave. The sensors were tested in a perfused rotating bioreactor supporting a BHK‐21 (baby hamster kidney) cell culture over one 28‐day, one 43‐day, and one 180‐day cell runs. The sensors were initially calibrated in sterile phosphate‐buffered saline (PBS) against a blood‐gas analyzer (BGA), and then used continuously during the entire cell culture without recalibration. In the 180‐day cell run, two oxygen sensors were employed; one interfaced at the outlet of the bioreactor and the other at the inlet of the bioreactor. The DO concentrations determined by both sensors were compared with those sampled and measured regularly with the BGA reference. The sensor outputs were found to correlate well with the BGA data throughout the experiment using a single calibration, where the DO of the culture medium varied between 25 and 60 mm Hg at the bioreactor outlet and 80–116 mm Hg at the bioreactor inlet. During all 180 days of culture, the precision and the bias were ±5.1 mm Hg and −3.8 mm Hg at the bioreactor outlet, and ± 19 mm Hg and −18 mm Hg at inlet. The sensor dynamic range is between 0 and 200 mm Hg and the response time is less than 1 minute. The resolution of the sensor is 0.1 mm Hg at 50 mm Hg, and 0.25 mm Hg at 130 mm Hg. © 2004 Wiley Periodicals, Inc.
Enzymatic labeling of a single chain variable fragment of an antibody with alkaline phosphatase by microbial transglutaminase
Authors: Takazawa Takeshi , Kamiya Noriho , Ueda Hiroshi , Nagamune Teruyuki 
Published: April 2004

AbstractFunctional cross‐linking of a single chain Fv fragment of anti‐hen egg‐white lysozyme antibody (scFv) and alkaline phosphatase (AP) was explored using microbial transglutaminase (MTG) from Streptomyces mobaraensis. A specific peptidyl linker for MTG was genetically fused to the N‐terminus of each protein and the resultant proteins were obtained separately by bacterial expression. The recombinant peptide‐tagged scFv and AP were site‐specifically cross‐linked by MTG through the extra peptidyl linkers in vitro, which mainly yielded the heterodimer (i.e., scFv‐AP conjugate). The enzymatic cross‐linking reaction had little influence on either the antigen‐binding ability of the scFv moiety or the enzymatic activity of the AP moiety of the conjugate, allowing use within an enzyme‐linked immunosorbent assay. The results obtained suggest that the enzymatic approach with MTG facilitates the posttranslational construction of functional fusion proteins. © 2004 Wiley Periodicals, Inc.
Production and characterization of liquid‐core capsules made from cross‐linked acrylamide copolymers for biotechnological applications
Authors: Wyss A. , von Stockar U. , Marison I.W. 
Published: April 2004

AbstractA novel chemistry has been developed for the production of capsules composed of a hydrophobic liquid core surrounded by a cross‐linked polyacrylamide/alginate membrane. These liquid‐core capsules may be used in capsular perstraction for the removal of inhibitory products from bioprocesses and bioconversions. They have the advantage of having a high surface area to promote rapid mass transfer, while separation of the organic core phase from the aqueous environment by the capsule membrane prevents the formation of stable emulsions and potential problems associated with toxicity of the organic phase for microbial cells or enzymes. Monodisperse spherical liquid‐core capsules of between 800 μm and 1.6 mm diameter, with high mechanical resistance, have been prepared by co‐extrusion, using the jet break‐up technique. Capsules produced from a solution of MBA/total monomer (5%) were found to be more elastic and have a higher burst force when exposed to chelating agents such as phosphate or citrate. The mechanical resistance was unaffected by buffer solutions in the pH range 4–9 and after sterilization at 121°C for 20 min. Capsules having membranes composed of a copolymer of acrylamide and N‐hydroxymethylacrylamide exhibited even higher mechanical stability toward chelating agents. © 2004 Wiley Periodicals, Inc.
Morphologically structured model for antitumoral retamycin production during batch and fed‐batch cultivations of Streptomyces olindensis
Authors: Giudici Reinaldo , Pamboukian Celso R. D. , Facciotti Maria Cândida R. 
Published: April 2004

AbstractA morphologically structured model is proposed to describe trends in biomass growth, substrate consumption, and antitumoral retamycin production during batch and fed‐batch cultivations of Streptomyces olindensis. Filamentous biomass is structured into three morphological compartments (apical, subapical, and hyphal), and the production of retamycin, a secondary metabolite, is assumed to take place in the subapical cell compartment. Model accounts for the effect of glucose as well as complex nitrogen source on both the biomass growth and retamycin production. Laboratory data from bench‐scale batch and fed‐batch fermentations were used to estimate some model parameters by nonlinear regression. The predictive capability of the model was then tested for additional fed‐batch and continuous experiments not used in the previous fitting procedure. The model predictions show fair agreement to the experimental data. The proposed model can be useful for further studies on process optimization and control. © 2004 Wiley Periodicals, Inc.