bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemo‐Enzymatic Approach to Statin Side‐Chain Building Blocks
Authors: Öhrlein R. , Baisch Gabriele 
Published: June 2003

AbstractA versatile statin side‐chain building block is obtained by an enzymatic desymmetrisation of the symmetrical glutaric acid diethyl ester. The monoacid is produced in almost quantitative yield in the desired high optical purity. The monoacid is easily converted to the corresponding acid chloride, which is a key compound to be elaborated to some statin side‐chain derivatives. The optically active C‐5 chain is subsequently elongated by two carbon atoms and syn‐reduced to the final diol fragment.
Membrane Aerated Hydrogenation: Enzymatic and Chemical Homogeneous Catalysis
Authors: Greiner Lasse , Müller Daniela H. , van den Ban Eyke C. D. , Wöltinger Jens , Wandrey Christian , Liese Andreas 
Published: June 2003

AbstractAmong the most successful systems for homogeneous catalysis, hydrogenation catalysts capable of activating molecular hydrogen, take outstanding roles in research laboratories and in industry. To open up the field of continuous catalytic hydrogenations a novel membrane reactor concept was developed and successfully applied for hydrogenations with dihydrogen both for chemical and for enzymatic catalysis. The hydrogenase I of the archaeon Pyrococcus furiosus was utilized for the continuous hydrogenation of NADP+ to NADPH with recycling of the enzyme by means of ultrafiltration. The well known PyrPhos‐Rh system was used for the enantioselective synthesis of an amino acid derivative by hydrogenation.
Biocatalytic Preparation of N‐Glycolylneuraminic Acid, Deaminoneuraminic Acid (KDN) and 9‐Azido‐9‐deoxysialic Acid Oligosaccharides
Authors: Blixt Ola , Paulson James C. 
Published: June 2003

AbstractA facile approach for preparative synthesis of sialyloligosaccharides containing N‐glycolylneuraminic acid, deaminoneuraminic acid, and two 9‐azido derivatives is described. Synthesis is accomplished by use of 6‐carbon mannose/mannosamine precursors employing an aldolase, CMP‐sialic acid synthetase, and sialyltransferase. Using a combination of five different sialyltransferases and various acceptor substrates, 16 sialosides representing sequences found in glycoproteins and glycolipids were synthesized with typical yields of 60–80%.
Mixed Aromatic Acyloin Condensations with Recombinant Benzaldehyde Lyase: Synthesis of α‐Hydroxydihydrochalcones and Related α‐Hydroxy Ketones
Authors: Sanchez‐Gonzalez Monica , Rosazza John P. N. 
Published: June 2003

AbstractRecombinant benzaldehyde lyase (BAL), expressed and purified from E. coli strain JM‐109, was used to catalyze the condensation of a series of methoxybenzaldehydes and phenylacetaldehyde in the synthesis of α‐(R)‐hydroxydihydrochalcones. Enantiomerically pure 1‐hydroxy‐1,3‐diphenylpropan‐2‐ones and o‐anisoin were also obtained as products of the BAL reaction. The R absolute configurations of chiral centers were determined by CD spectroscopy. α‐(R)‐Hydroxydihydrochalcones and 1‐hydroxy‐1,3‐diphenylpropan‐2‐ones are valuable synthons for chemoenzymatic syntheses of flavonoids. This is the first synthesis of α‐(R)‐hydroxydihydrochalcones by a microbial enzyme.
Preparative Enzymatic Synthesis of the Acylglucuronide of Mycophenolic Acid
Authors: Kittelmann Matthias , Rheinegger Urs , Espigat Aude , Oberer Lukas , Aichholz Reiner , Francotte Eric , Ghisalba Oreste 
Published: June 2003

AbstractThe acylglucuronide (3) of mycophenolic acid (1) was enzymatically synthesised on a preparative scale (450 mg substrate) under optimised reaction conditions with 51% conversion. By screening 9 liver homogenates from 8 vertebrate species, it was shown that only with liver homogenate from horse as the catalyst were the acyl‐ (3) and the O‐glucuronide (2) were formed in a ca. 1 : 1 ratio. With homogenates from other sources, the O‐glucuronide (2) was produced in high excess. By optimising the concentration of the co‐substrate UDP‐glucuronic acid and the reaction temperature, the conversion to the acylglucuronide (3) was increased from initially 34 to 55% and the ratio of acyl‐ (3) to O‐glucuronide (2) from 1.5 : 1 to 3.9 : 1. The reaction was also performed continuously in an enzyme membrane reactor, however, with lower conversion yield and therefore, higher specific UDP‐glucuronic acid consumption.
Chemo‐Enzymatic Method for the Synthesis of Statine, Phenylstatine and Analogues
Authors: Kambourakis Spiros , Rozzell J. David 
Published: June 2003

AbstractA chemo‐enzymatic method for the synthesis of statine [(3S,4R)‐4‐amino‐3‐hydroxy‐6‐methylheptanoic acid] and statine analogues with natural and unnatural side chains is described. The key step of the synthesis is the diastereoselective reduction of a 2‐alkyl‐substituted 3‐ketoglutarate by an NADPH‐dependent ketoreductase. Two chiral centers are generated in one step, and high yields of a single stereoisomer are obtained (80–90% yield, 90–99% de). Subsequent chemical or enzymatic regio‐selective hydrolysis to the mono‐acid followed by rearrangement under Curtius or Hofmann conditions generates the final statines.
Attitudes and distress levels in women at risk to carry a BRCA1/BRCA2 gene mutation who decline genetic testing
Authors: Lodder Litanja , Frets Petra G. , Trijsburg R. Willem , Klijn Jan G.M. , Seynaeve Caroline , Tilanus Madeleine M.A. , Bartels Carina C.M. , Meijers‐Heijboer E Johanna , Verhoog Leon C. , Niermeijer Martinus F. 
Published: May 2003

AbstractGenetic testing enables women at risk for hereditary breast and/or ovarian cancer to find out whether they have inherited the gene mutation, and if so, to opt for undergoing frequent surveillance and/or prophylactic surgery. However, the option to know about one's genetic status is not always seen as a benefit by women at risk. Motives for declining genetic testing were explored in 13 women at 25% or 50% risk to be a BRCA1/BRCA2 mutation carrier, who participated in a surveillance program for breast/ovarian cancer (the non‐tested group). We hypothesized that high anxiety might be an important motive to decline testing. In addition, we investigated whether the non‐tested group differed from a reference group of women who did undergo the test (tested group; n = 85) with regard to biographical factors, experience with cancer in relatives, and personality traits. Most non‐tested women (10/13) were satisfied with participating in the surveillance program. Four reported to feel emotionally unprepared to cope with the consequences of testing. Compared with the tested group, the non‐tested women had similar mean distress levels (which were not high), but a higher education level, they were more often childless, showed more reluctance towards prophylactic surgery, were younger when first confronted with a relative affected with breast/ovarian cancer, and were longer aware of the genetic nature of the disease. This study showed that women were more likely to have thoroughly reflected on their decision not to undergo genetic testing, than to deny the whole issue due to high anxiety. Being confronted at a relatively young age with breast/ovarian cancer in a relative, and being aware of the genetic risk for a many years, may have resulted in the risk for cancer becoming an integrated part of their lives. However, generalization of these results to women who neither underwent the test nor participated in a surveillance program should be considered with caution.© 2003 Wiley‐Liss, Inc.
Deletion of chromosome region 18q21.1 → 18q21.3 in a patient without clinical features of the 18q‐ phenotype
Authors: Engelen J.J.M. , Moog U. , Weber J. , Haagen A.A.M. , van Uum C.M.J. , Hamers A.J.H. 
Published: May 2003

AbstractIn a 16‐month‐old boy referred because of developmental delay and asymmetric motor development, chromosome analysis showed an aberrant chromosome 18 in all 25 metaphases examined. The chromosome aberration was initially interpreted either as an interstitial deletion of chromosome region 18q21.1 → 18q21.3 or an unbalanced translocation involving the distal part of the long arm of chromosome 18. Chromosome microdissection in combination with fluorescence in situ hybridization demonstrated that the aberrant chromosome 18 had an interstitial deletion, the karyotype being: 46,XY,del(18)(q21.1q21.3). At age 27 months, his development was moderately retarded. He showed craniofacial asymmetry but no other anomalies. The clinical and cytogenetic findings are compared with previously reported patients with a terminal or interstitial deletion in the long arm of chromosome 18. © 2003 Wiley‐Liss, Inc.
Terminal deletion of chromosome 5p in a patient with phenotypical features of Lujan–Fryns syndrome
Authors: Stathopulu E. , Ogilvie C. Mackie , Flinter F.A. 
Published: May 2003

AbstractWe report a young man with phenotypical features suggestive of Lujan–Fryns syndrome and behaviour of an autistic spectrum disorder, who has a subtle terminal deletion of the short arm of chromosome 5. Individuals reported previously with a similar chromosomal abnormality have had developmental delay and a ‘breathy, raspy’ voice. It may be appropriate to consider screening patients with a phenotype suggestive of Lujan–Fryns syndrome by fluorescence in situ hybridisation (FISH) using a probe for the subtelomeric region of the short arm of chromosome 5. © 2003 Wiley‐Liss, Inc.
Development of the pharyngeal arches
Authors: Graham Anthony 
Published: May 2003

AbstractThe oro‐pharyngeal apparatus has its origin in a series of bulges that is found on the lateral surface of the embryonic head, the pharyngeal arches. The development of the pharyngeal arches is complex involving a number of disparate embryonic cell types: ectoderm, endoderm, neural crest and mesoderm, whose development must be co‐ordinated to generate the functional adult apparatus. In the past, most studies have emphasised the role played by the neural crest, which generates the skeletal elements of the arches, in directing pharyngeal arch development, but it has also become apparent that the other tissues of the arches, most notably the endoderm, also plays a prominent role in directing arch development. Thus pharyngeal arch development is more complex, and more consensual, than was previously believed. © 2003 Wiley‐Liss, Inc.
Alport syndrome with diffuse leiomyomatosis
Authors: Anker Martina C. , Arnemann Joachim , Neumann Katrin , Ahrens Peter , Schmidt Helga , König Rainer 
Published: May 2003

AbstractAlport syndrome (AS) is a hereditary nephropathy with hematuria progressing to end‐stage renal failure (ESRF), sensorineural deafness, and specific eye signs (lenticonus, macular flecks, and congenital cataracts). Inheritance is X‐linked in about 85% of the cases, caused by different mutations in the COL4A5 gene. Rarely AS is seen in combination with diffuse leiomyomatosis (DL). DL is a tumorous process involving smooth muscle cells, mostly of the esophagus, but also of the tracheobronchial tree and the female genital tract. Characteristically, the patients have deletions of the 5′‐end of both the COL4A5 and the COL4A6 genes, respectively. We here present a 9‐year‐old boy who was admitted because of a newly diagnosed sensorineural deafness. He was born with cataracts and presented symptoms of dysphagia and bronchial irritation in the first year of life. Macroscopic hematuria was first noticed at 2 years during a febrile infection. Since early childhood the boy suffered from severe constipation. Taking together these symptoms, the diagnosis of Alport syndrome with diffuse leiomyomatosis (AS‐DL) has to be considered. Genetic analysis demonstrated the predicted deletion of the COL4A5/COL4A6 genes. © 2003 Wiley‐Liss, Inc.
Further delineation of the phenotype associated with heterozygous mutations in ZFHX1B
Authors: Wilson Meredith , Mowat David , Dastot‐Le Moal Florence , Cacheux Valère , Kääriäinen Helena , Cass Danny , Donnai Dian , Clayton‐Smith Jill , Townshend Sharron , Curry Cynthia , Gattas Michael , Braddock Stephen , Kerr Bronwyn , Aftimos Salim , Zehnwirth Harry , Barrey Catherine , Goossens Michel 
Published: May 2003

AbstractMutations or deletions involving ZFHX1B (previously SIP1) have recently been found to cause one form of syndromic Hirschsprung disease (HSCR), associated with microcephaly, mental retardation, and distinctive facial features. Patients with the characteristic facial phenotype and severe mental retardation, but without HSCR, have now also been shown to have mutations in this gene. Mutations of ZFHX1B are frequently associated with other congenital anomalies, including congenital heart disease, hypospadias, renal tract anomalies, and agenesis of the corpus callosum (ACC). We present the clinical data and mutation analysis results from a series of 23 patients with this clinical syndrome, of whom 21 have proven ZFHX1B mutations or deletions (15 previously unpublished). Two patients with the typical features (one with and one without HSCR) did not have detectable abnormalities of ZFHX1B. We emphasize that this syndrome can be recognized by the facial phenotype in the absence of either HSCR or other congenital anomalies, and needs to be considered in the differential diagnosis of dysmorphism with severe mental retardation +/− epilepsy. © 2003 Wiley‐Liss, Inc.
Analysis of 40 sporadic or familial neonatal and pediatric cases with severe unexplained respiratory distress: Relationship to SFTPB
Authors: Tredano Mohammed , Griese Matthias , de Blic Jacques , Lorant Tifenn , Houdayer Claude , Schumacher Silja , Cartault François , Capron Frédérique , Boccon‐Gibod Liliane , Lacaze‐Masmonteil Thierry , Renolleau Sylvain , Delaisi Bertrand , Elion Jacques , Couderc Rémy , Bahuau Michel 
Published: May 2003

AbstractWe have analyzed surfactant protein B (SP‐B) and its encoding gene (SFTPB, MIM 178640) in 40 unrelated pediatric patients with unexplained respiratory distress (URD). There was high consanguinity (eight kindreds) and an underlying autosomal recessive trait could be inferred in most cases, with overall high sex ratio (32/17) suggesting proband's gender to impact on penetrance. The clinical/biological presentations fitted into three major nosologic frameworks. I: SP‐B deficiency (nine probands), complete or incomplete, with homozygous/compoundly heterozygous mutations identified (six probands), including one from the population isolate of Réunion Island (496delG). In addition, there was a consanguineous kindred in which incomplete deficiency was unambiguously unlinked to SFTPB. II: pulmonary alveolar proteinosis (PAP, 19 probands), with typical storage of PAS‐positive material within the alveoli with foamy macrophages and variable interstitial reaction, which was diagnosed in most patients from Réunion Island. In contrast to previously published findings, mutation and/or segregation analyses excluded SFTPB as a disease locus, although slight metabolic derangement related to SP‐B and/or mild SFTPB changes could somehow contribute to disease. III: URD without evidence for SP‐B deficiency or PAP (12 probands), equally unlinked to SFTPB, although a single patient had a possibly causal, maternally‐derived, heterozygous genetic change (G4521A). The population frequency of five known and four novel SNPs was studied, providing as many potential markers for pulmonary disease related to SFTPB. Overall, URD was found to be heterogeneous, both phenotypically and genetically, even in population isolates where a founder effect might have been expected. When disease loci are identified, patient genotyping will be crucial as a diagnostic aid, for devising proper treatment, and as a basis for genetic counseling. © 2003 Wiley‐Liss, Inc.
Spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL)
Authors: Tsirikos Athanasios I. , Mason Dan E. , Scott Charles I. , Chang Wei‐Ning 
Published: May 2003

AbstractSpondyloepimetaphyseal dysplasia with joint laxity (SEMDJL) is a distinctive form of skeletal dysplasia characterized by severe dwarfism, generalized articular hypermobility, and progressive spinal malalignment. We report on a patient with SEMDJL, who presented with all the characteristic orthopedic manifestations of the disorder, required multiple operative procedures, and has the longest reported follow‐up and survival into adulthood with a favorable outcome. We describe all the clinical and radiographic findings that can allow an early diagnosis of this type of skeletal dysplasia, which can lead to profound disability with potentially lethal spinal and pulmonary complications in early childhood. In view of the severe clinical and genetic implications, diagnostic precision is of vital importance, particularly since the disorder is currently believed to be more common than initially reported. © 2003 Wiley‐Liss, Inc.
Short trunk stature, brachydactyly, and platyspondyly in three sibs: A new form of brachyolmia or a new skeletal dysplasia?
Authors: Tüysüz Beyhan , Üngür Savaş 
Published: May 2003

AbstractWe present a 27‐year‐old girl with short trunk stature, generalized rectangular platyspondyly and strike precocious calcification of costal cartilage. She had also brachydactyly, small nails, strabismus and delay of menarche. Her 16‐year‐old sister had also short trunk stature with severe kyphoscoliosis, hearing loss, brachydactyly, platyspondyly and mild precocious calcification of costal cartilages. Their 12‐year‐old brother had short trunk stature, kyphoscoliosis, brachydactyly, and platyspondyly but did not show precocious calcification of costal cartilage. The patients shared the following features: short trunk stature, brachydactyly, severe rectangular platyspondyly, broad and short femoral necks and hypoplasia of the ileum. In addition, the older sister had strike precocious calcification of costal cartilage while her sister and brother had severe kyphoscoliosis. Although short trunk stature and severe rectangular platyspondyly without significant epiphyseal or metaphyseal changes were in favor of Hobaek type brachyolmia, this diagnosis was not considered, both because, there were no specific radiological findings of this syndrome, such as elongated vertebral bodies extending beyond the pedicles laterally and all of the patients had brachydactyly which was not present in Hobaek type brachyolmia. The parents were healthy and first cousins signifying autosomal recessive inheritance. We considered that the patients could be affected by a new distinct autosomal recessive type brachyolmia or a new skeletal dysplasia. © 2003 Wiley‐Liss, Inc.
Pregnancy outcome and prenatal diagnosis of sex chromosome abnormalities in Hawaii, 1986–1999
Authors: Forrester Mathias B. , Merz Ruth D. 
Published: May 2003

AbstractSex chromosome abnormalities such as Turner syndrome, Klinefelter syndrome, triple X syndrome, and 47,XYY can be prenatally diagnosed and electively terminated. This investigation examined the pattern of pregnancy outcome of prenatally and postnatally diagnosed sex chromosome abnormalities in Hawaii during 1986–1999 and calculated prenatal diagnosis and subsequent elective termination rates for various factors. Data were obtained from a statewide population‐based birth defects registry. The study included 205 detected sex chromosome abnormality cases of which 93 (45%) were live births, 18 (9%) late fetal deaths, 37 (18%) early fetal deaths, and 57 (28%) elective terminations. Pregnancy outcome distribution varied by type of sex chromosome abnormality. Prenatal diagnosis was reported for 132 (64%) of the cases, of which 46 (35%) were subsequently electively terminated. Eleven cases were elective terminations where the sex chromosome abnormality was diagnosed after delivery. Elective termination rates subsequent to prenatal diagnosis differed by sex chromosome abnormality, being highest for 45,X (54%), followed by 47,XXY (46%), 47,XYY (29%), and 47,XXX (17%). Although prenatal diagnosis rates increased significantly over the time period (P = 0.006), the subsequent elective termination rate declined slightly, albeit the trend was not statistically significant (P = 0.440). The prenatal diagnosis rate was highest for the 35–39‐year maternal age group, although this age group did not have subsequent elective termination rates higher than other maternal age groups. Pregnancy outcome distribution and prenatal diagnosis and subsequent elective termination of sex chromosome abnormalities appeared to depend on the type of sex chromosome abnormality, year of delivery, and maternal age. © 2003 Wiley‐Liss, Inc.
First‐year mortality rates for selected birth defects, Hawaii, 1986–1999
Authors: Forrester Mathias B. , Merz Ruth D. 
Published: May 2003

AbstractBirth defects have been the leading cause of infant death in the United States for over the last decade. However, there is little population‐based data on the first‐year mortality rates for many specific birth defects and the factors that may affect these mortality rates. This investigation examined the first‐year mortality rates for 54 selected birth defects of various organ systems in Hawaii during 1986–1999 using data from a population‐based birth defects registry and evaluated the impact of the presence of chromosomal abnormalities and other structural birth defects and the year of delivery on the mortality rates. Mortality rates varied widely by defect, being highest for anencephaly (100%), trisomy 13 (82%), and trisomy 18 (74%), while no first‐year deaths were reported for glaucoma, bladder exstrophy, and persistent cloaca. The majority (36 of 54 or 67%) of the birth defects had a mortality rate of less than 25%. Among the 51 structural birth defects, 38 (75%) had higher first‐year mortality rate for cases with chromosomal abnormalities and 42 (82%) had higher first‐year mortality rates for cases with other major structural birth defects. The mortality rate among 1986–1992 deliveries was higher than the mortality rate among 1993–1999 deliveries for 37 (69%) of the 54 birth defects. This study indicates that first‐year mortality rates vary widely by type of birth defect, although the mortality rate for the majority of birth defects is relatively low. The presence of a chromosomal abnormality or other structural birth defect increases the mortality rate, and mortality rates for the majority of birth defects have declined in Hawaii during the study period. © 2003 Wiley‐Liss, Inc.
Vocal cord abnormalities in Williams syndrome: A further manifestation of elastin deficiency
Authors: Vaux Keith K. , Wojtczak Henry , Benirschke Kurt , Jones Kenneth Lyons 
Published: May 2003

AbstractWilliams syndrome (WS) is due to a deletion in the WS critical region at 7q11.23 which includes the elastin gene (ELN). One of the most characteristic features of this disorder is a harsh, brassy, or hoarse voice but the etiology of the vocal characteristics are unknown. We report two patients with WS who had bilateral vocal cord abnormalities, bringing to four the number of children with WS in whom such defects have been documented. We suggest that vocal cord abnormalities may be a far more common feature of WS than has been previously suspected, and that mild vocal cord dysfunction caused by abnormal vocal cord elastin may be the cause of the hoarse voice in this condition. © 2003 Wiley‐Liss, Inc.