bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between nonsyndromic cleft lip with or without cleft palate and the glutamic acid decarboxylase 67 gene in the Japanese population
Authors: Kanno Kiyoshi , Suzuki Yoichi , Yamada Atsushi , Aoki Yoko , Kure Shigeo , Matsubara Yoichi
Published: April 2004

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is one of the most common craniofacial malformations. Both genetic and environmental factors are involved in the pathogenesis. In addition to its role as an inhibitory neurotransmitter, γ‐aminobutyric acid (GABA) synthesized by glutamic acid decarboxylase (GAD) is presumed to play a role in normal embryonic, especially facial, development. This notion has been substantiated by the fact that Gad67 knockout mice have been shown to have cleft palate. We hypothesized that GAD67 may be involved in the development of NSCLP and investigated the possible association between the GAD67 gene (GAD67) and NSCLP in Japanese patients. We screened 50 probands for single nucleotide polymorphisms (SNPs) in GAD67 using denaturing high performance liquid chromatography (DHPLC) and found seven SNPs. Since two SNPs showed complete linkage disequilibrium (LD) to the other SNPs, we constructed a 5‐locus haplotype of GAD67. The frequency distribution of the haplotype differed between NSCLP patients and controls (P = 0.0028). The frequency of −445A, −292A, −147G, 111C, and IVS9–39T haplotype in the NSCLP patients was significantly lower than that in controls (P = 0.00098). In a transmission disequilibrium test (TDT) in 99 parent–offspring trios, we found −445C, −292C, −147G, 111C, and IVS9–39C haplotype was preferentially transmitted to the patients with cleft lip and palate (P = 0.0077). Our data suggest that GAD67 is involved in the pathogenesis of NSCLP in the Japanese population. © 2003 Wiley‐Liss, Inc.
Non‐neurogenic sarcomas in four children and young adults with neurofibromatosis type 1
Authors: Coffin Cheryl M. , Cassity Jamie , Viskochil David , Lor Randall R. , Albritton Karen
Published: April 2004

It is well known that children and young adults with neurofibromatosis type 1 (NF1) have a higher risk for non‐neurogenic sarcomas than the general population, in addition to an increased risk for malignant peripheral nerve sheath tumor. When non‐neurogenic sarcomas occur in early childhood, a subsequent malignant peripheral nerve sheath tumor can occur as a second malignant neoplasm, especially after alkylating agent chemotherapy and irradiation. This report includes the clinicopathologic features of non‐neurogenic sarcomas and secondary malignant peripheral nerve sheath tumor in the context of four cases of NF1. The purpose is to emphasize that early diagnosis of NF1 and recognition of potential manifestations of non‐neurogenic sarcomas are important for clinical care of these patients and their families. © 2004 Wiley‐Liss, Inc.
Gene responsible for mitochondrial myopathy and sideroblastic anemia (MSA) maps to chromosome 12q24.33
Authors: Casas Kari , Bykhovskaya Yelena , Mengesha Emebet , Wang Dai , Yang Huiying , Taylor Kent , Inbal Aida , Fischel‐Ghodsian Nathan
Published: April 2004

Mitochondrial myopathy and sideroblastic anemia (MSA) is a rare autosomal recessive disorder of oxidative phosphorylation and iron metabolism. Individuals with MSA present with weakness and anemia in late childhood and may become dependent on blood transfusions. Recently, we reported affected sibling pairs from a Jewish‐Iranian kindred living in the US [Casas and Fischel‐Ghodsian, 2003]. A genome scan and fine mapping of DNA from this family revealed homozygous alleles in the affected individuals, and a multipoint logarithm of the odds (lod) score of 3.3, within 2.3 mb of chromosome 12q24.33. Previously, Inbal et al. [1995: Am J Med Genet 55:372–378] described siblings with a similar clinical phenotype who lived in Israel but originated from the same Iranian town as the US family. Focused analysis of DNA from the Israeli family confirmed the presence of identical, homozygous alleles in the affected of the US and Israeli families within 1.2 mb of chromosome 12q24.33. Combined multipoint linkage analysis revealed a maximum lod score of 5.41 at the 132 cM position of chromosome 12. Therefore, in these two families of Jewish‐Iranian descent, a disease gene for MSA maps to a 1.2 mb region of chromosome 12q24.33. This region contains 6 well described genes (SFRS8, MMP17, ULK1, PUS1, EP400, and GALNT9) and at least 15 additional putative transcripts. The known genes are expressed in multiple tissues and lack a function specific to mitochondria, making none an obvious candidate. The eventual identification of the disease gene in MSA is expected to provide insight into the tissue specificity and phenotypic variability of mitochondrial disease. © 2004 Wiley‐Liss, Inc.
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

Solitary 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

We 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

Smoking 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

Tardive 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

We 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

One 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

Until 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

Towards 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

Brain 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

Das 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.
Old Clusters with New Tricks: Engineering S⋅⋅⋅S Interactions and Novel Physical Properties in Sulfite‐Based Dawson Clusters
Authors: Long De‐Liang , Kögerler Paul , Cronin Leroy
Published: April 2004

Zwei pyramidale Sulfitionen wirken als Template bei der Bildung neuer 18‐Molybdosulfit‐Dawson‐Cluster. Die Wechselwirkung zwischen den beiden SO32−‐Ionen wurde mit DFT‐Rechnungen untersucht. Das [Mo18O54(SO3)2]4−‐Ion ist das erste diskrete thermochrome Polyoxometallat: Es ändert seine Farbe von Hellgelb bei 77 K nach Dunkelrot bei 500 K (siehe Bild).
Titelbild: Excess Electron Transport Through DNA: A Single Electron Repairs More than One UV‐Induced Lesion (Angew. Chem. 14/2004)
Authors: Giese Bernd , Carl Barbara , Carl Thomas , Carell Thomas , Behrens Christoph , Hennecke Ulrich , Schiemann Olav , Feresin Emiliano
Published: April 2004

Die elektronenkatalysierte Reparatur von Thymindimeren in Doppelstrang‐DNA schildern B. Giese, T. Carell, O. Schiemann et al. in ihrer Zuschrift auf S. 1884 ff. Der Transport eines Elektrons ausgehend von einer modifizierten Thyminbase entlang der DNA lässt sich als mehrstufiger Hopping‐Prozess beschreiben. Trifft das Elektron auf ein Thymindimer (gebildet durch Photocycloaddition benachbarter Thyminreste), so regeneriert eine Retrocyclisierung die beiden Thyminbasen, und das Elektron setzt seine Reise fort.
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

The 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

For 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

Functional 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

A 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

A 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.
Determination of external and internal mass transfer limitation in nitrifying microbial aggregates
Authors: Wilén Britt‐Marie , Gapes Daniel , Keller Jürg
Published: April 2004

In this article we present a study of the effects of external and internal mass transfer limitation of oxygen in a nitrifying system. The oxygen uptake rates (OUR) were measured on both a macro‐scale with a respirometric reactor using off‐gas analysis (Titrimetric and Off‐Gas Analysis (TOGA) sensor) and on a micro‐scale with microsensors. These two methods provide independent, accurate measurements of the reaction rates and concentration profiles around and in the granules. The TOGA sensor and microsensor measurements showed a significant external mass transfer effect at low dissolved oxygen (DO) concentrations in the bulk liquid while it was insignificant at higher DO concentrations. The oxygen distribution with anaerobic or anoxic conditions in the center clearly shows major mass transfer limitation in the aggregate interior. The large drop in DO concentration of 22–80% between the bulk liquid and aggregate surface demonstrates that the external mass transfer resistance is also highly important. The maximum OUR even for floccular biomass was only attained at much higher DO concentrations (≈8 mg/L) than typically used in such systems. For granules, the DO required for maximal activity was estimated to be >20 mg/L, clearly indicating the effects of the major external and internal mass transfer limitations on the overall biomass activity. Smaller aggregates had a larger volumetric OUR indicating that the granules may have a lower activity in the interior part of the aggregate. © 2004 Wiley Periodicals, Inc.
Highly selective membranes in protein ultrafiltration
Authors: Feins Meredith , Sirkar Kamalesh K.
Published: April 2004

A new ultrafiltration technique based on a multimembrane stack has been developed to fractionate solutes closer in size than conventionally possible. The technique is illustrated here by obtaining a pure protein product from a binary protein mixture. By employing membranes in series without any gaskets or spacers in‐between, ultrafiltration is carried out to separate two proteins relatively close in molecular weight or size. Flat YM30 regenerated cellulose membranes, all of the same molecular weight cut‐off (MWCO) 30,000, are stacked together in the desired number, and ultrafiltration takes place. The membrane rejection of a protein is amplified with each additional membrane, ultimately resulting in a completely rejected species. Complete purification of the more permeable protein may be achieved regardless of the physicochemical condition that may be optimal or suboptimal for selective separation by a single membrane. Two systems, myoglobin and β‐lactoglobulin, as well as myoglobin and α‐lactalbumin were studied, under various operating conditions. The solvent flux reduction encountered when each membrane is added may also be avoided, by operating at increased pressure, while still achieving the desired purification. Cleaning in situ is achievable with reproducible experimental results before and after on‐line cleaning. The results clearly demonstrate that multimembrane stacks can be used for fractionation of proteins that are quite close in molecular weight/size. © 2004 Wiley Periodicals, Inc.
Encapsulation of crosslinked penicillin G acylase aggregates in lentikats: Evaluation of a novel biocatalyst in organic media
Authors: Wilson Lorena , Illanes Andrés , Pessela Benevides C. C. , Abian Olga , Fernández‐Lafuente Roberto , Guisán José M.
Published: April 2004

The encapsulation of crosslinked enzyme aggregates (CLEA) of penicillin G acylase into a very rigid polymeric matrix based on polyvinyl alcohol (LentiKats) has been used successfully to improve the inadequate mechanical properties of CLEA. This encapsulation decreased CLEA activity by only around 40%. As compensation, a significant improvement in the stability of the CLEA in the presence of organic solvents was detected. This could be related to the highly hydrophilic environment inside the LentiKats biocatalysts: Partition experiments showed that the concentration of dioxane inside LentiKats was lower than in the reaction medium. In fact, thermal stability was about the same as in the corresponding CLEA. This permitted great improvement in the reaction rate for thermodynamically controlled synthesis of a model antibiotic (using phenylacetic acid and 7‐amino‐deacetoxycefalosporanic acid). Even more importantly, yields could be improved by using LentiKats‐encapsulated CLEA, very likely by a favorable product/substrate partition. Thus, this very simple technique not only provides an efficient technique for solving the mechanical stability problem associated with CLEA, but also greatly improves the behavior of CLEA in organic media. © 2004 Wiley Periodicals, Inc.
Randomized clinical trial to assess the effect of an educational programme designed to improve nurses' assessment and recording of postoperative pain
Authors: Ravaud P , Keïta H , Porcher R , Durand-Stocco C , Desmonts J M , Mantz J
Published: April 2004

Background

The aim of this study was to evaluate the impact of an intervention designed to improve postoperative pain assessment and recording by nurses.

Methods

This cluster randomized clinical trial included two intervals of 3 months each: a preintervention observational study (period 1) followed by a period of intervention (period 2). Six surgical wards were randomly assigned to receive either an experimental intervention, including educational seminars for nurses on pain, pain assessment and the use of a visual analogue scale (n = 3), or standard care (control group; n = 3). The main outcome measures were the percentage of patients in whom pain was assessed, number of pain assessments per patient and postoperative pain intensity scores.

Results

A total of 2278 patients were included. Significant improvements were found in the percentage of patients in whom pain was assessed and the number of daily pain assessments per patient in the intervention group between periods 1 and 2. In contrast, these outcomes were unchanged between the two intervals in wards randomized to standard care. During period 2, pain scores at 48 h were significantly decreased in the intervention wards compared with those in the control group.

Conclusion

An educational programme dedicated to nurses strongly increased the use of regular pain assessment, and may have contributed to a modest improvement in postoperative analgesia.
Posterior laparostomy through the bed of the 12th rib to drain retroperitoneal infection after endoscopic sphincterotomy
Authors: Doglietto G B , Pacelli F , Caprino P , Alfieri S , Tortorelli A P , Mutignani M
Published: April 2004

Background

Duodenal perforation occurs in 0·4–1 per cent of endoscopic procedures. The best therapeutic approach for periampullary injury is controversial; initially the treatment is generally conservative, but sometimes large retroperitoneal infections develop that require surgery.

Methods

Six patients with an extensive retroperitoneal collection and unstable sepsis as a consequence of periampullary duodenal perforation sustained during endoscopic retrograde cholangiopancreatography were treated by right posterior laparostomy through the bed of the 12th rib.

Results

The sepsis was managed effectively by an open posterior approach, resulting in spontaneous closure of the duodenal leak after a mean(s.d.) of 14·5(5·2) days. No hospital death or major complication was recorded. Late incisional hernia developed in one patient.

Conclusion

The technique of posterior laparostomy through the bed of the 12th rib provided adequate debridement and drainage of upper and lower parts of the retroperitoneal space involved by infection following periampullary duodenal perforation. Good control of retroperitoneal sepsis and duodenal secretions resulted in spontaneous closure of the duodenal leak, avoiding the need for more complex intra-abdominal procedures.
Late stent thrombosis (> 1 year) following clopidogrel withdrawal after brachytherapy treatment: Need to assess aspirin resistance?
Authors: Jiménez‐Quevedo Pilar , Angiolillo Dominick J. , Bernardo Esther , Sabaté Manel
Published: April 2004

We report on a patient presenting with late thrombosis of a stent 15 months after being treated with intracoronary brachytherapy. It occurred 17 days after clopidogrel withdrawal while maintaining treatment with aspirin. At the time of stent thrombosis, evaluation of platelet aggregation was performed, revealing a suboptimal response to aspirin. Pathophysiological insights of aspirin resistance and clinical implications are reviewed. Catheter Cardiovasc Interv 2004;62:39–42. © 2004 Wiley‐Liss, Inc.
Myocardial resistance assessed by guidewire‐based pressure‐temperature measurement: In vitro validation
Authors: Aarnoudse Wilbert , van den Berg Petra , van de Vosse Frans , Geven Maartje , Rutten Marcel , van Turnhout Mark , Fearon William , De Bruyne Bernard , Pijls Nico
Published: April 2004

By injecting a few cubic centimeters of saline into the coronary artery and using thermodilution principles, mean transit time (Tmn) of the injectate can be calculated and is inversely proportional to coronary blood flow. Because microvascular resistance equals distal coronary pressure (Pd) divided by myocardial flow, the product Pd · Tmn provides an index of myocardial resistance (IMR). In this in vitro study in a physiologic model of the coronary circulation, we compared IMR to true myocardial resistance (TMR) at different degrees of myocardial resistance and at different degrees of epicardial stenosis. Absolute blood flow was varied from 42 to 203 ml/min and TMR varied from 0.39 to 1.63 dynes · sec/cm5. Inverse mean transit time correlated well to absolute blood flow (R2 = 0.93). Furthermore, an excellent correlation was found between IMR and TMR (R2 = 0.94). IMR was independent on the severity of epicardial stenosis and thus specific for myocardial resistance. Thus, using one single guidewire, both fractional flow reserve and IMR can be measured simultaneously as indexes of epicardial and microvascular disease, respectively, enabling separate assessment of both coronary arterial and microvascular disease. Catheter Cardiovasc Interv 2004; 62:56–63. © 2004 Wiley‐Liss, Inc.
Endovascular repair of a giant carotid pseudoaneurysm with the use of Viabahn stent graft
Authors: Gupta Kamal , Dougherty Kathy , Hermman Heinz , Krajcer Zvonimir
Published: April 2004

A 72‐year‐old woman presented with a large pulsatile anterior right neck mass with compressive symptoms of dysphagia and hoarseness. This was due to a large (6 cm by 4 cm) postcarotid endarterectomy pseudoaneurysm of the right common carotid artery. Successful endovascular exclusion of the pseudoaneurysm was performed with a Viabahn stent graft with significant decrease in the size on follow‐up. Other endovascular options such as coil embolization and thrombin injection are also discussed. It is important to exclude infection as the cause of postendarterectomy pseudoaneurysm before considering endovascular repair over surgical repair. Catheter Cardiovasc Interv 2004;62:64–68. © 2004 Wiley‐Liss, Inc.
The NUGGET study: NIR ultra gold‐gilded equivalency trial
Authors: Reifart Nicolaus , Morice Marie‐Claude , Silber Sigmund , Benit Edouard , Hauptmann K.E. , de Sousa Eduardo , Webb John , Kaul Upendra , Chan Charles , Thuesen Leif , Guagliumi Giulio , Cobaugh Michael , Dawkins Keith
Published: April 2004

This study should clarify whether the gold‐coated NIROYAL stent is equivalent to the stainless steel NIR stent. Patients were randomized to either NIR stent (n = 298) or a NIROYAL stent (n = 305). The primary endpoint was the minimum lumen diameter of the target lesion at 6 months postprocedure. Secondary endpoints focused on clinical events. At 30 days, adverse events were similar in both groups. At 6 months, the minimal lumen diameter was 1.83/1.64 mm (P < 0.001; 95% CI = 0.08–0.30) and the angiographic restenosis rate was 20.6%/37.7% (P < 0.001; 95% CI = −24.7 to −9.3) for NIR/NIROYAL. The 6‐month MACE rates were NIR 7.4% and NIROYAL 10.5% (95% CI = −7.7 to 1.4). Compared to stainless steel stent, the NIROYAL stent demonstrated a smaller minimal lumen diameter, a higher late loss (i.e., higher neointimal hyperplasia in spite of a significantly better initial gain), with higher restenosis and similar MACE rates at 6 months. Catheter Cardiovasc Interv 2004;62:18–25. © 2004 Wiley‐Liss, Inc.
Bladed balloon angioplasty for peripheral pulmonary artery stenosis
Authors: Sugiyama Hisashi , Veldtman Gruchen R. , Norgard Gunnar , Lee Kyong‐Jin , Chaturvedi Rajiv , Benson Lee N.
Published: April 2004

Treatment for peripheral pulmonary artery stenosis is challenging, and conventional balloon angioplasty has not proved to be universally effective. Evaluated was the efficacy of bladed balloon (BB) dilation to address vessels resistant to conventional high‐pressure (10–15 atm) balloon angioplasty (BA). Thirty‐one procedures were performed on 14 children with age range 1 month to 15 years. The diameter of the BB ranged from 3 to 8 mm. After BB dilation, all children had subsequent conventional BA (balloon size range, 3–10 mm). The minimal lumen diameter (MLD) before and after the procedure, whether there was a waist at initial BA, and BB diameter‐to‐MLD ratio before the procedure were measured. A > 50% increase in MLD was considered successful. Four children had Williams syndrome, two children Alagille syndrome, five children Fallot's tetralogy, and three miscellaneous lesions. The resistant stenosis was located in the right central pulmonary artery in 6, right branch pulmonary artery in 7, left central pulmonary artery in 6, and left branch pulmonary artery in 12 lesions. Median BB diameter was 253% (117–440%) of the MLD and increased from 2.0 ± 0.7 to 3.2 ± 0.8 mm (P < 0.0001), with a mean increase of 73% ± 62%. There was an inverse relationship between the MLD before and increase after the procedure (r = 0.75; P < 0.001). The BB diameter‐to‐MLD ratio before procedure was significantly associated with the increase in MLD (r = 0.70; P < 0.001). After the procedure, 18 of the 31 procedures were considered successful. In all successful procedures, the BB diameter was greater than twice the MLD before the procedure. Comparing children with Williams and Alagille syndrome with the remaining eight children, there were no significant differences in the increase in MLD. A small aneurysm and thrombus were noticed in two and three children, respectively, but no fatal complications were reported. BB angioplasty is effective for resistant peripheral pulmonary artery stenosis when conventional BA fails. The diameter of the BB should be larger than twice the minimal luminal diameter of the stenotic lesion. Catheter Cardiovasc Interv 2004;62:71–77. © 2004 Wiley‐Liss, Inc.
A Versatile Polypeptide Platform for Integrated Recognition and Reporting: Affinity Arrays for Protein–Ligand Interaction Analysis
Authors: Enander Karin , Dolphin Gunnar T. , Liedberg Bo , Lundström Ingemar , Baltzer Lars
Published: April 2004

A molecular platform for protein detection and quantification is reported in which recognition has been integrated with direct monitoring of target‐protein binding. The platform is based on a versatile 42‐residue helix–loop–helix polypeptide that dimerizes to form four‐helix bundles and allows site‐selective modification with recognition and reporter elements on the side chains of individually addressable lysine residues. The well‐characterized interaction between the model target‐protein carbonic anhydrase and its inhibitor benzenesulfonamide was used for a proof‐of‐concept demonstration. An affinity array was designed where benzenesulfonamide derivatives with aliphatic or oligoglycine spacers and a fluorescent dansyl reporter group were introduced into the scaffold. The affinities of the array members for human carbonic anhydrase II (HCAII) were determined by titration with the target protein and were found to be highly affected by the properties of the spacers (dissociation constant Kd=0.02–3 μM). The affinity of HCAII for acetazolamide (Kd=4 nM) was determined in a competition experiment with one of the benzenesulfonamide array members to address the possibility of screening substance libraries for new target‐protein binders. Also, successful affinity discrimination between different carbonic anhydrase isozymes highlighted the possibility of performing future isoform‐expression profiling. Our platform is predicted to become a flexible tool for a variety of biosensor and protein‐microarray applications within biochemistry, diagnostics and pharmaceutical chemistry.
Photoinduced Electron Transfer in Multiporphyrinic Interlocked Structures: The Effect of Copper(I) Coordination in the Central Site
Authors: Flamigni Lucia , Talarico Anna Maria , Chambron Jean‐Claude , Heitz Valérie , Linke Myriam , Fujita Norifumi , Sauvage Jean‐Pierre
Published: April 2004

Photoinduced processes have been determined in a [2]catenane containing a zinc(II) porphyrin, a gold(III) porphyrin, and two free phenanthroline binding sites, Zn–Au+, and in the corresponding copper(I) phenanthroline complex, Zn–Cu+–Au+. In acetonitrile solution Zn–Au+ is present in two different conformations: an extended one, L, which accounts for 40 % of the total, and a compact one, S. In the L conformation, the electron transfer from the excited state of the Zn porphyrin to the gold–porphyrin unit (k = 1.3×109 s−1) is followed by a slow recombination (k = 8.3×107 s−1) to the ground state. The processes in the S conformation cannot be clearly resolved but a charge‐separated (CS) state is rapidly formed and decays with a lifetime on the order of fifty picoseconds. In the catenate Zn–Cu+–Au+, the zinc–porphyrin excited state initially transfers energy to the CuI–phenantholine unit, producing a metal‐to‐ligand charge‐transfer (MLCT) excited state localized on the copper complex with a rate k = 1.4×109 s−1. From this excited state the transfer of an electron to the gold–porphyrin unit takes place, producing the CS state Zn–Cu2+–Au., which decays with a lifetime of 10 ns. The results are discussed in comparison with the closely related [2]rotaxane, in which a further charge shift from the copper center to the zinc–porphyrin unit leads to the fully CS state. Even in the absence of such full charge separation, it is shown that the lifetimes of the CS states are increased by a factor of about 2–2.5 over those of the corresponding rotaxanes.
On the Inverse Perovskites M3TO (M: Ca, Sr, Yb; T: Si, Ge, Sn, Pb).
Authors: Velden A. , Jansen M.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis and Crystal Structures of New Palladium(II)—Gallium(III) Complexes with Bridging Halogenide Ligands.
Authors: Gorlov Mikhail , Fischer Andreas , Kloo Lars
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Compounds with Pentelide Dumbbells M2: AI11M6 and AII11M10 (A: Rb, Cs, Ba; M: Sb, Bi).
Authors: Emmerling Franziska , Laengin Nina , Pickhard Frank , Wendorff Marco , Roehr Caroline
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Cs2Cr4O13: A New Structure Type Among Alkali Tetrachromates.
Authors: Kolitsch Uwe
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
The High‐Temperature Modification of Zinc catena‐Polyphosphate, β‐Zn(PO3)2.
Authors: Weil Matthias
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.