bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical variability in a Noonan syndrome family with a new PTPN11 gene mutation
Authors: Bertola Débora Romeo , Pereira Alexandre C. , Oliveira Paulo S.L. de , Kim Chong A. , Krieger José Eduardo
Published: September 2004

Noonan syndrome (NS) is an autosomal dominant disorder comprising short stature, facial dysmorphism, short and/or webbed neck, heart defects, and cryptorchidism in males. The gene responsible for the disorder (PTPN11) was recently identified, and explains 30–50% of the cases clinically diagnosed as NS. Cardiofaciocutaneous (CFC) syndrome, a similar but distinct entity, is characterized by relative macrocephaly, characteristic facial appearance, ectodermal abnormalities (sparse and friable hair, sparse eyebrows, hyperkeratotic skin), congenital heart defects, and growth and mental retardation. We describe on a young woman who presents clinical features of NS (short stature, triangular facies, with dowslanting palpebral fissures and apparent hypertelorism, webbed neck, pulmonary stenosis, bleeding diathesis, prominent corneal nerves), but with a more prominent ectodermal involvement (sparse and very coarse hair, sparse eyebrows and eyelashes) and developmental delay/mental retardation, which are characteristic of CFC patients. Sequencing of the PTPN11 gene showed a T411M substitution, not previously described in patients with NS. The same mutation was found in her mother and older sister, not initially considered to be affected by NS, but with very subtle clinical findings compatible with this diagnosis. Molecular dynamic studies indicate that this new mutation, similar to other previously described mutations, favors a more active protein conformation. However, the main disruptive effect is not directly in the catalytic domain, suggesting that the location of this mutation could make the protein more susceptible to gene–gene or gene–environment interactions. Atypical cases of NS should be screened for mutations in the PTPN11 gene and in the case of a positive result, first‐degree relatives should also be tested for the specific mutation. © 2004 Wiley‐Liss, Inc.
Deficiency of pyruvate dehydrogenase caused by novel and known mutations in the E1α subunit
Authors: Cameron Jessie M. , Levandovskiy Valeriy , MacKay Neviana , Tein Ingrid , Robinson Brian H.
Published: September 2004

Pyruvate dehydrogenase (PDH)‐complex deficiency (OMIM 312170) is a clinically heterogeneous disorder, with phenotypes ranging from fatal lactic acidosis (LA) in the newborn to chronic neurological dysfunction. To date, over 80 different mutations have been identified in the PDHA1 gene in patients with PDH complex deficiency, which are thus thought to contribute to the PDH deficient phenotype. We have identified 14 additional patients with total PDH complex deficiency, all of whom were found to contain mutations within the PDHA1 gene (E1α subunit). The mutations include both missense mutations and duplications. Eight of these patients had novel mutations, and the remaining had mutations that have been identified previously in PDH complex deficient patients, with residual fibroblast activity ranging from 2.4 to 69% of control values. The nature of these mutations illustrates the variability in phenotype for a given gene defect, with intermittent ataxia being the mildest presentation, Leigh syndrome being the most common and severe neonatal LA the most severe. © 2004 Wiley‐Liss, Inc.
Costello syndrome with pancreatic islet cell hyperplasia
Authors: Dickson Patricia I. , Briones Norman Y. , Baylen Barry G. , Jonas Adam J. , French Samuel W. , Lin Henry J.
Published: September 2004

A 3‐month‐old boy with Costello syndrome (CS) developed respiratory distress and fatal arrhythmias. An autopsy showed cardiac hypertrophy, mild coarctation of the aorta, and pancreatic islet cell hyperplasia. To our knowledge, this is the first report of a pancreatic abnormality in CS. Islet cell hyperplasia has also been observed in leprechaunism, Beckwith–Wiedemann (BWS), and Simpson–Golabi–Behmel syndromes. The syndromes are thought to involve abnormal insulin or insulin‐like growth factor (IGF) pathways. Clinical similarities among these disorders and CS, together with the finding of islet cell hyperplasia, suggest that they may be related. © 2004 Wiley‐Liss, Inc.
Renal disease in Arima syndrome is nephronophthisis as in other Joubert‐related Cerebello–oculo–renal syndromes
Authors: Kumada Satoko , Hayashi Masaharu , Arima Kunimasa , Nakayama Hiroshi , Sugai Kenji , Sasaki Masayuki , Kurata Kiyoko , Nagata Michio
Published: September 2004

Clinicopathological features of the renal disease in Arima syndrome were studied in five autopsy cases. All cases showed insidious development of end‐stage renal disease during childhood, preceded by polyuria/polydipsia, anemia, and growth failure. Decreased urinary concentrating ability and excessive sodium loss were the characteristic laboratory findings. Gross examination showed that both kidneys were small and showed multiple cysts of various sizes. The histological examinations revealed chronic sclerosing tubulo‐interstitial nephropathy with cystic tubuli predominantly located at cortico‐medullary areas. These observations suggest that the renal disease in Arima syndrome is in accordance with nephronophthisis both clinically and pathologically. Contrary to the previous literature which described that Arima syndrome can be distinguished from other Joubert‐related cerebello–oculo–renal syndromes by its unique renal disease, i.e., cystic dysplastic kidney (CDK), our study indicates that the phenotype of the renal disease is common among these syndromes as well as abnormalities in other organs, suggesting the underlying similar molecular mechanisms. © 2004 Wiley‐Liss, Inc.
Feeling at risk: How women interpret their familial breast cancer risk
Authors: van Dijk Sandra , Otten Wilma , van Asperen Christi J. , Timmermans Danielle R.M. , Tibben Aad , Zoeteweij Moniek W. , Silberg Sylvia , Breuning Martijn H. , Kievit Job
Published: September 2004

Women's inaccuracy in recalling their breast cancer risk, even immediately after genetic counseling, has received much attention. However, scarce data are available about how women describe their risk in their own words and about what the risk information actually means to them. The present study aims to address interpretations questions and to assess whether these are congruent with the objective risk. Face‐to‐face interviews were conducted with 123 women immediately after their (initial) counseling session. N‐Vivo software was used to describe the data. The level of accuracy of recall depended strongly on the leniency of the criterion applied. For example, the level of verbal accuracy ranged from 25.8% (an exact match with the verbal label) to 98.4% (a more global awareness of having a high versus a low risk). In assessing the significance of personal risk information, we identified a wide variety of risk beliefs, and stress and coping responses. In general, women associated their risk with the medical options, for example, breast screening, that were available for them given their risk status. The results indicate that the accuracy of recall might be a limited outcome measure for the effectiveness of genetic counseling. First, this is because the level of accuracy of recall depends on how rigorously accuracy is defined. Secondly, because the probability of occurrence is just one of the elements comprising perceived risk, accuracy might rather apply to the distress, and to risk management behaviors that are elicited by the risk information. These beliefs that women hold about their risk status, and concomitant levels of stress should play a prominent role in genetic counseling. © 2004 Wiley‐Liss, Inc.
Synthesis and characterization of a novel nitrogen‐containing flame retardant
Authors: Hu Xiao‐Ping , Li Wei‐Yi , Wang Yu‐Zhong
Published: September 2004

The lowering of ignitability and flammability of polyethylene (PE) and the production of fire‐retarding materials has become an urgent problem because of the demand of fire safety. In our article, a new charring agent (CA), a derivative of triazines, was synthesized by charging 2‐amino‐4,6‐dichloro‐s‐triazines and diethylenetriamine into a reactor to conduct the solution polycondensation reaction, and the synthetic conditions of monomer and CA, such as temperature, time, etc., were investigated. Both the monomer and the resulting polymer were characterized by mass spectrum (MS), Fourier transform infrared (FTIR) spectroscopy, 1HNMR, and elemental analysis. The intrinsic viscosities and flame‐retardancy property of CA were also studied. It was found that the incorporation of ammonium polyphosphate (APP) and CA into low‐density polyethylene (LDPE) has a distinct effect on thermal and flame‐retardancy behavior. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1556–1561, 2004
Novel sulfonated poly(ether ether ketone ketone) derived from bisphenol S
Authors: Li Xianfeng , Na Hui , Lu Hui
Published: September 2004

A series of sulfonated poly(ether ether ketone ketone)s derived from bisphenol S were prepared by nucleophilic polycondensation. They showed high thermal resistance and good solubility. Most of the polymers were easily cast into tough membranes. The swelling of the membranes (6.02–16.02%) was lower than that of Nafion membranes, and the ion‐exchange capacity of the membranes (0.67–1.44) was higher than that of Nafion membranes. The proton conductivity of the membranes was 0.022–0.125 s/cm. They could be used as proton‐exchange membranes in fuel cells. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1569–1574, 2004
Influence of mixing procedures and mica addition on properties of NR/BR vulcanizates. I
Authors: Castro Daniele F. , Suarez João Carlos Miguez , Nunes Regina C. R. , Visconte Leila L. Y.
Published: September 2004

Elastomeric compositions of natural rubber (NR) and polybutadiene rubber (BR) in a 1 : 1 ratio (w/w), with mica in the range 0–30 phr, were investigated. For all compositions the same formulation was used but two different additives incorporation sequences were followed. The results of the tests showed that the mechanical performance is sequence‐dependent, as the two elastomers have very different rheometric characteristics. It was also observed that mica, when present in amounts of 20 and 30 phr, improves the mechanical properties. Scanning electron microscopy (SEM) permitted the observation of the fracture behavior of each composition, and dynamic mechanical thermal analysis (DMTA) suggested different migration tendencies of the additives in each phase, thus corroborating the differences found for the mechanical properties. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1575–1585, 2004
Chitosan supported palladium catalyst. VI. Nitroaniline degradation
Authors: Vincent Thierry , Peirano Francisco , Guibal Eric
Published: September 2004

A chitosan‐supported palladium catalyst was prepared by immobilization of palladium on glutaraldehyde crosslinked chitosan followed by in situ chemical reduction. This catalyst was successfully used for the degradation of 4‐nitroaniline (4‐NA) in the presence of sodium formate, used as the hydrogen donor. The reaction product was 1,4‐phenylenediamine. The degradation was favored by acidic pH. A 10 to 15 excess of formate (compared to 4‐NA) is required to achieve complete degradation of the substrate. The reaction appears to be limited to the external layers of the catalyst: small particle size is required to optimize the degradation kinetics. Alternatively, an increase of catalyst dosage is required to increase kinetic rates but at the expense of palladium consumption. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1634–1642, 2004
Applying Tikhonov regularization to process the kinetic data of polymerization
Authors: Yeow Y. Leong , Pradhana Stephanus I , Tan Heather C. L. , Leong Yee‐Kwong
Published: September 2004

Most experimental polymerization kinetic data are in the form of degree of polymerization versus time plots. However, to explore kinetic models it is more useful to have the data as polymerization rate versus degree of polymerization plots. Converting degree of polymerization into rate is an ill‐posed problem in that if inappropriate methods are used the noise in the data will be amplified, leading to unreliable results. This paper describes a procedure, based on Tikhonov regularization, to perform this conversion. The procedure is independent of kinetic models and keeps noise amplification under control. Its performance is demonstrated using several sets of published polymerization kinetic data. In each case the computed rates are used to determine the parameters in the rate expression proposed in the original papers. Modified rate expressions will also be explored. The ease with which such investigations can be performed highlights the advantages of this new procedure. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1625–1633, 2004
SiC microsphere derived from phenolic resin—Ethyl silicate heterogeneous precursors with carbothermic reduction
Authors: Narisawa Masaki , Ukon Hiroshi , Mabuchi Hiroshi , Okamura Kiyohito , Kurachi Yasuo
Published: September 2004

Heterogeneous precursors for SiC particles were synthesized from viscous phenolic resin and tetraethyl orthosilicate with hastening ethanol removal process in a concentrated state. In the pyrolysis products, spherical carbon domains with diameter of several micrometers were embedded in the SiO2‐C matrix. After the carbothermic reduction process at 2073 K, SiC‐C spheres were obtained with an SiC yield of ∼80%, while the carbon domains acted as templates of the SiC‐C spheres with complete disappearance of the SiO2‐C matrix area. After the carbon burned out, some of the spheres possessed a hollow structure. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1612–1618, 2004
Controversies concerning the anatomical definition of the conduction tissues
Authors: Anderson Robert H. , Christoffels Vincent M. , Moorman Antoon F.M.
Published: September 2004

Conduction across the atrioventricular junctions had long been controversial, with arguments raging as to whether such conduction was myogenic or neurogenic. The landmark study of Tawara in 1906 established the existence of an axis of histologically specialized myocardial cells contained within fibrous sheaths as being responsible for rapid conduction from the atrial to the ventricular myocardium. Keith and Flack then demonstrated that the atrial impulse was generated in the sinus node, with subsequent slowing within the atrioventricular node of Tawara. The detailed reviews of Aschoff and Monckeberg then emphasized the morphological features that permit unequivocal recognition of the nodes, along with rapidly conducting tracts. It is now pertinent that we remember these original criteria for anatomical recognition as we discuss the steps involved in the development of these conducting structures from their embryologic primordiums. In this review, we restate the criteria of Aschoff and Monckeberg, then discuss their relevance to the developmental issues, emphasizing that all myocardial cells have the potential to conduct. The important issues, therefore, are the changes that occur as the heart itself changes from a solitary muscular tube, already possessing the capacity t generate an electrocardiogram, to the four‐chambered structure we recognize in postnatal life. Anat Rec (Part B: New Anat) 280B:8–14, 2004. © 2004 Wiley‐Liss, Inc.
Pharmacokinetics, metabolism and excretion of intravenous [l4C]‐palonosetron in healthy human volunteers
Authors: Stoltz Randall , Parisi Simona , Shah Ajit , Macciocchi Alberto
Published: September 2004

Palonosetron (Aloxí(R), Onícít(R)) is a potent, single stereoisomeric 5‐HT3 receptor antagonist developed to prevent chemotherapy‐induced nausea and vomiting. The pharmacokinetics and metabolic disposition of a single intravenous [14C]‐palonosetron (10 µg/kg, 0.8 µCi/kg) bolus dose were evaluated in six healthy volunteers (three males, three females) using serial blood, plasma, urine and fecal samples obtained over 10 days. The safety, tolerability and cardiac effects were assessed. Radiolabeled metabolic characterization revealed that unchanged palonosetron accounted for 71.9% of the total radioactivity in plasma over 96 h, with an extensive distribution volume (8.34 l/kg) and mean plasma elimination half‐life of 37 h. Approximately 83% of the dose was recovered in urine (∼40% as unchanged drug, with 50% metabolized; M9 and M4 were the major metabolites) and 3.4% in feces. Hydrolysis of urine samples suggests that the metabolites are not β‐glucuronide or sulfate conjugates of the parent drug or metabolites. The blood to plasma concentration ratio of the total radioactivity was 1.2, on average, indicating little selective partitioning in erythrocytes. Palonosetron was generally well tolerated; headache was the most frequently reported adverse event. Electrocardiograms and 72 h Holter monitoring revealed no clinically significant changes. Palonosetron circulates in plasma mainly as the parent drug. Renal elimination is the primary excretion route, with parent drug and metabolites M9 and M4 accounting for the majority of palonosetron disposition. These results indicate that both renal and hepatic routes are involved in the elimination of palonosetron from the body. Copyright © 2004 John Wiley & Sons, Ltd.
The dice of fate: thecsdgene and how its allelic composition regulates sexual development in the honey bee,Apis mellifera
Authors: Beye Martin
Published: September 2004

Perhaps 20% of known animal species are haplodiploid: unfertilized haploid eggs developinto males and fertilized diploid eggs into females. Sex determination in such haplodiploid species does not rely on a difference in heteromorphic sex chromosome composition but the genetic basis has been elucidated in some hymenopteran insects (wasps, sawflies, ants, bees). In these species, the development into one sex or the others depends on an initial signal whether there is only one allele or two different alleles of a single gene, thecomplementary sex determiner(csd), in the zygotic genome. The gene has been most‐recently identified in the honey bee and has been found to encode an arginine serine‐rich (SR) type protein. Heterozygosity generates an active protein that initiates female development while hemizygosity/homozygosity results in a non‐active CSD protein and default male development. I will discuss plausible models of how the molecular decision of male and female is made and implemented. Comparison to hierarchies of dipteran insects suggests that SR‐type protein has facilitated the differentiation of sex‐determining systems and hierarchies. BioEssays 26:1131–1139, 2004. © 2004 Wiley Periodicals, Inc.
Microvascular development: learning from pancreatic islets
Authors: Konstantinova Irena , Lammert Eckhard
Published: September 2004

Microvascular development is determined by the interplay between tissue cells and microvascular endothelial cells. Because the pancreatic islet is an organ composed mainly of endothelial and endocrine cells, it represents a good model tissue for studying microvascular development in the context of a tissue. In this review, we will describe the special morphology of islet capillaries and its role in the physiologic function of islets: secretion of insulin in response to blood glucose levels. We will speculate on how islet‐secreted VEGF‐A generates a permeable endothelium that allows insulin to pass quickly into the blood stream. In addition, we speculate on how endothelial cells might form a capillary lumen within the islets. At the end, we look at the islet microvasculature from a medical point of view, thus describing its critical role during type I diabetes and islet transplantation. BioEssays 26:1069–1075, 2004. © 2004 Wiley Periodicals, Inc.
Segments and parasegments in Arthropods: a functional perspective
Authors: Deutsch Jean S.
Published: September 2004

I review how both the parasegmental and segmental frames are used in constructing the body plan of the arthropods. The parasegment is the primary genetic unit, as shown by Hox gene expression, and the parasegmental design is maintained in the nerve cord. It is, however, not maintained in the epidermis, where the cuticle grooves are segmental, and in the musculature, which is segmental in organisation. This frame shift is reflected in the sensory and motor nerve connections between the ganglia and the periphery. I suggest that the need for movement in an organism equipped with a hard exoskeleton was the functional constraint that shaped this apparently complex mode of development. BioEssays 26:1117–1125, 2004. © 2004 Wiley Periodicals, Inc.
Plant coloration undermines herbivorous insect camouflage
Authors: Lev‐Yadun Simcha , Dafni Amots , Flaishman Moshe A. , Inbar Moshe , Izhaki Ido , Katzir Gadi , Ne'eman Gidi
Published: September 2004

The main point of our hypothesis “coloration undermines camouflage” is that many color patterns in plants undermine the camouflage of invertebrate herbivores, especially insects, thus exposing them to predation and causing them to avoid plant organs with unsuitable coloration, to the benefit of the plants. This is a common case of “the enemy of my enemy is my friend” and a visual parallel of the chemical signals that plants emit to call wasps when attacked by caterpillars. Moreover, this is also a common natural version of the well‐known case of industrial melanism, which illustrates the great importance of plant‐based camouflage for herbivorous insects and can serve as an independent test for our hypothesis. We claim that the enormous variations in coloration of leaves, petioles and stems as well as of flowers and fruits undermine the camouflage of invertebrate herbivores, especially insects. We assume that the same principle might operate in certain animal–parasite interactions. Our hypothesis, however, does not contrast or exclude other previous or future explanations of specific types of plant coloration. Traits such as coloration that have more than one type of benefit may be selected for by several agents and evolve more rapidly than ones with a single type of advantage. BioEssays 26:1126–1130, 2004. © 2004 Wiley Periodicals, Inc.
The dawn of bilaterian animals: the case of acoelomorph flatworms
Authors: Baguñà Jaume , Riutort Marta
Published: September 2004

The origin of the bilaterian metazoans from radial ancestors is one of the biggest puzzles in animal evolution. A way to solve it is to identify the nature and main features of the last common ancestor of the bilaterians (LCB). Recent progress in molecular phylogeny has shown that many platyhelminth flatworms, regarded for a long time as basal bilaterians, now belong to the lophotrochozoan protostomates. In contrast, the LCB is now considered a complex organism bearing several features of modern bilaterians. Here we discuss an alternative view, in which acoelomorph (Acoela + Nemertodermatida) flatworms, which do not belong to the Platyhelminthes, represent the earliest extant bilaterian clade. Sequences from ribosomal and other nuclear genes, Hox cluster genes, and reinterpretation of some morphological features strongly support the basal position of acoelomorphs arguing against a complex LCB. This reconstruction backs the old planuloid–acoeloid hypothesis and may help our understanding of the evolution of body axes, Hox genes and the Cambrian explosion. BioEssays 26:1046–1057, 2004. © 2004 Wiley Periodicals, Inc.
A bigger mouse? The rat genome unveiled
Authors: Hancock John M.
Published: September 2004

Rattus norvegicus is an important experimental organism and interesting to evolutionary biologists. The recently published draft rat genome sequence1 provides us with insights into both the rat's evolution and its physiology. We learn more about genome evolution and, in particular, the adaptive significance of gene family expansions and the evolution of rodent genomes, which appears to have decelerated since the divergence of mouse and rat. An important observation is that some regions of genomes, many in noncoding regions, show very high sequence conservation, while others show unexpectedly fast evolution. Both of these may be pointers to functional significance. BioEssays 26:1039–1042, 2004. © 2004 Wiley Periodicals, Inc.
Leptin leads hypothalamic feeding circuits in a new direction
Authors: Harrold Joanne A.
Published: September 2004

A decade ago, leptin (from the greek lepto meaning ‘thin’) was identified as the product of the ob gene.1 This adipocyte‐derived hormone was found to suppress feeding and stimulate thermogenesis, and was thus proposed as a mediator in a negative feedback loop that controls body adiposity. This discovery led to a rapid revolution in the understanding of neurobiological mechanisms regulating obesity. However, while leptin's first life was as an adipostat, it is now known to have a wide range of additional neuroendocrine, metabolic and behavioural functions in the CNS and periphery. Remarkably, the pleiotropic nature of the hormone continues to be extended with the recent publication of two papers that expand on leptin's neurobiological actions in the CNS.2,3 They indicate novel regulatory roles for the hormone in both synaptic plasticity and axon guidance. Crucially, in light of the rising incidence of obesity in modern society, both of the studies reveal leptin‐mediated links between nutrition and neurodevelopment, findings that have further implications for leptin's role in the regulation of energy homeostasis. BioEssays 26:1043–1045, 2004. © 2004 Wiley Periodicals, Inc.
Outcome after implantation of a novel prosthetic anal sphincter in humans
Authors: Finlay I G , Richardson W , Hajivassiliou C A
Published: September 2004

Background

A novel prosthetic anal sphincter (PAS) has been developed that aims to occlude by flattening and angulating the bowel, reproducing the action of the puborectalis muscle. The safety of the PAS has been confirmed in biomechanical, in vitro and long-term animal survival studies. The Medical Devices Agency approved implantation in 12 patients.

Methods

The PAS was placed in the pelvis around the anorectal junction via a transabdominal approach in 12 patients with severe faecal incontinence. The device was activated 6 weeks after surgery. Fibreoptic examination of the mucosa below the device was undertaken at various intervals during review.

Results

At a median follow-up of 59 (range 30–72) months nine of the 12 patients had a functioning PAS. There were no device-related infective complications after the initial operation but one patient developed pseudomembranous colitis and had the device removed. The PAS was effective in restoring continence in ten of 11 patients. Median (range) Cleveland Clinic continence scores improved from 16 (7–20) before to 3 (0–7) after surgery. In two patients the PAS was eventually removed owing to infection after revisional surgery. There was no clinical or histological evidence of gastrointestinal mucosal ischaemia.

Conclusion

The PAS was effective in restoring continence. There was no device-related infection after the initial operation, no device erosion and no clinical or histological evidence of gastrointestinal ischaemia.
Systematic review of genetic influences on the prognosis of colorectal cancer
Authors: Anwar S , Frayling I M , Scott N A , Carlson G L
Published: September 2004

Background

In terms of genetics, colorectal cancer is one of the best understood of all malignant diseases. Genetic influences on prognosis may have far-reaching implications, especially for the design of surgical and chemoradiotherapeutic regimens. However, their significance in determining prognosis remains unclear. This study aimed to review the literature on the specific role of key genes in determining the survival of patients with colorectal cancer.

Methods

A Medline search was carried out to identify all original scientific papers relating colorectal cancer genetics to patient survival, up to December 2002. Cochrane and Embase databases were also searched. Identified articles were retrieved and searched carefully for additional information. This review includes K-ras, p53, DCC, NM23 and DNA mismatch repair genes.

Results and conclusion

Conflicting evidence exists as to the prognostic significance of genes commonly implicated in the pathogenesis of colorectal carcinoma. Possible causes for such discrepancy include differences in study methods and laboratory techniques, variable duration of follow-up, statistical differences in study power, and heterogeneity in study populations. Future studies should adopt standardized protocols to define clinically relevant genetic observations.
Sentinel node micrometastasis in breast cancer
Authors: Rutgers E J T
Published: September 2004

Extra information is not always valuable
Synthesis and Self‐Assembly of a Rigid Exotopic Bisphenanthroline Macrocycle: Surface Patterning and a Supramolecular Nanobasket
Authors: Kalsani Venkateshwarlu , Ammon Horst , Jäckel Frank , Rabe Jürgen P. , Schmittel Michael
Published: September 2004

The synthesis and characterisation of a rigid nanoscale macrocycle with two exotopic phenanthroline binding sites is reported. Scanning tunnelling microscopy (STM) at the solid–liquid interface reveals the formation of highly ordered monolayers of macrocycles with dimensions that are in good agreement with the calculated structure. Using the HETPHEN concept several bisheteroleptic coordination complexes with other phenanthrolines and a nanoscale basket assembly were prepared in presence of copper(I) ions. NMR spectroscopy, mass spectrometric data and elemental analysis point to three distinct isomers of the basket assembly in solution. A silver basket was prepared and readily converted to its copper analogue. Electrospray ionisation (ESI)‐MS and spectrophotometric investigations provided additional mechanistic insight into the assembly process. Hence, the exotopic bisphenanthroline macrocycle in combination with HETPHEN concept proves to be very effective in controlling the compositional aspects of multicomponent self‐assembly.
Structure–Property Correlation of a New Family of Organogelators Based on Organic Salts and Their Selective Gelation of Oil from Oil/Water Mixtures
Authors: Trivedi Darshak R. , Ballabh Amar , Dastidar Parthasarathi , Ganguly Bishwajit
Published: September 2004

Organic salts based on dicyclohexylamine and substituted/unsubstituted cinnamic acid exhibit efficient gelation of organic fluids, including selective gelation of oil from an oil/water mixture. Among the cinnamate salts, dicyclohexylammonium 4‐chlorocinnamate (1), 3‐chlorocinnamate (2), 4‐bromocinnamate (3), 3‐bromocinnamate (4), 4‐methylcinnamate (5) and the parent cinnamate (6) are gelators, whereas 2‐chlorocinnamate (7), 2‐bromocinnamate (8), 3‐methylcinnamate (9), 2‐methylcinnamate (10) and hydrocinnamate (11) are non‐gelators. Non‐gelation behaviour of 11 and various benzoate derivatives 12–18 indicate the significance of an unsaturated backbone in the gelation behaviour of the cinnamate salts. A structure–property correlation based on the single‐crystal structures of most of the gelators (1, 3, 5 and 6) and non‐gelators, such as 7, 8, 10–18, indicates that the prerequisite for the one‐dimensional (1D) growth of the gel fibrils is mainly governed by the 1D hydrogen‐bonded network involving the ion pair. All the non‐gelators show either two‐ (2D) or zero‐dimensional (0D) hydrogen‐bonded assemblies involving the ion pair. The molecular packing of the fibres in the xerogels of 1, 3, 5 and 6 has also been established on the basis of their simulated powder diffraction patterns, XRPD of bulk solids and xerogels. Ab initio quantum chemical calculations suggests that π–π interactions is not a contributing factor in the gelation process.
Ligand Bite Governs Enantioselectivity: Electronic and Steric Control in Pd‐Catalyzed Allylic Alkylations by Modular Fenchyl Phosphinites (FENOPs)
Authors: Goldfuss Bernd , Löschmann Thomas , Rominger Frank
Published: September 2004

Modular fenchyl phosphinites (FENOPs) containing different aryl units—phenyl (1), 2‐anisyl (2), or 2‐pyridyl (3)—are efficiently accessible from (−)‐fenchone. For comparison of the influence of the different aryl units on enantioselectivities and reactivities, these FENOPs were employed in Pd‐catalyzed allylic alkylations. The strongly chelating character of P,N‐bidentate 3 is apparent from X‐ray structures with PdCl2 ([Pd(3)Cl2]), and with allyl–Pd units in ([Pd(3)(η1‐allyl)] and [Pd(3)(η3‐allyl)]). FENOP3 gives rise to a PdL* catalyst of moderate enantioselectivity (42 % ee, R product). Surprisingly, higher enantioselectivities are found for the hemilabile, monodentate FENOPs 1 (83 % ee, S enantiomer) and 2 (69 % ee, S enantiomer). Only small amounts of 1 or 2 generate selective PdL* catalysts, while complete abolition of enantioselectivity appears with unselective PdL*2 species with higher FENOP concentrations in the cases of 1 or 2. Computational transition structure analyses reveal steric and electronic origins of enantioselectivities. The nucleophile is electronically guided trans to phosphorus. endo‐Allyl arrangements are favored over exo‐allyl orientations for 1 and 2 due to Pd–π–pyridyl interactions with short “side‐on” Pd‐aryl interactions. More remote “edge‐on” Pd–π–aryl interactions in 3 with Pd‐N(lp) coordination favor endo‐allyl units slightly more and explain the switch of enantioselectivity from 1 (S) and 2 (S) to 3 (R).
Towards Highly Fluorescent and Water‐Soluble Perylene Dyes
Authors: Kohl Christopher , Weil Tanja , Qu Jianqiang , Müllen Klaus
Published: September 2004

A systematic approach towards highly fluorescent, water‐soluble perylene‐3,4:9,10‐tetracarboxylic acid diimide chromophores is presented. Water solubility was introduced first through the attachment of four hydrophilic substituents onto thebayregion of the perylene dye. Positively and negatively charged groups were then applied to the chromophore, and their number and their distance from the aromatic scaffold were systematically varied. To suppress aggregation, the chromophore was further isolated within a dendritic shell. Such variation of structural features and a thorough investigation of the resulting optical properties facilitated the first synthesis of perylene‐3,4:9,10‐tetracarboxylic acid diimides combining the properties of water solubility and fluorescence quantum yields (FQYs) close to unity, which makes them attractive as high‐performance fluorescence probes in aqueous media.
Synthesis and Coordinating Ability of an Anionic Cobaltabisdicarbollide Ligand Geometrically Analogous to BINAP
Authors: Rojo Isabel , Teixidor Francesc , Viñas Clara , Kivekäs Raikko , Sillanpää Reijo
Published: September 2004

The anionic chelating ligand [1,1′‐(PPh2)2‐3,3′‐Co(1,2‐C2B9H10)2]− has been synthesized from [3,3′‐Co(1,2‐C2B9H11)2]− in very good yield in a one‐pot process with an easy work‐up procedure. The coordinating ability of this ligand has been studied with Group 11 metal ions (Ag, Au) and with transition‐metal ions (Pd, Rh). The two dicarbollide halves of the [1,1′‐(PPh2)2‐3,3′‐Co(1,2‐C2B9H10)2]− ligand can swing about one axis in a manner analogous to the constituent parts of BINAP and ferrocenyl phosphine derivatives. All these ligands function as hinges, with the most important property in relation to the coordination requirements of the metal being the P⋅⋅⋅P distance. [1,1′‐(PPh2)2‐3,3′‐Co(1,2‐C2B9H10)2]−, BINAP, ferrocenyl phosphine derivatives, and other hinge ligands present a range of different P⋅⋅⋅P separations, and consequently different coordination spheres and dispositions around metal cations. To account for these differences, the equation Dφ2 = D02 + 4 R2cos2(90−${{\varphi \over 2}}$) has been developed. It relates the P⋅⋅⋅P distance (Dφ) in a complex with the minimum P⋅⋅⋅P distance (D0) that is characteristic of the hinge‐type ligand.
Aldolase Antibody Activation of Prodrugs of Potent Aldehyde‐Containing Cytotoxics for Selective Chemotherapy
Authors: Sinha Subhash C. , Li Lian‐Sheng , Watanabe Shin‐ichi , Kaltgrad Eiton , Tanaka Fujie , Rader Christoph , Lerner Richard A. , Barbas Carlos F.
Published: September 2004

Prodrugs of potent aldehyde analogues of the anticancer drug doxorubicin (Dox) were synthesized. These prodrugs were efficiently activated by antibody 93F3 and no drug formation was observed in the absence of 93F3 in either phosphate buffered saline or cell culture media. In the presence of antibody 93F3, these prodrugs were activated and decreased the proliferation of human cancer cells in in vitro proliferation assays.
Synthesis, Light‐Harvesting and Energy‐Transfer Properties of Regioregular Silylene‐Spaced Alternating [(Donor‐SiMe2‐)n=1–3‐(Acceptor‐SiMe2)] Copolymers
Authors: Cheng Yen‐Ju , Luh Tien‐Yau
Published: September 2004

A series of silylene‐spaced alternating [(donor‐SiMe2)n=1–3‐(acceptor‐SiMe2)] copolymers 4–6 was synthesized by rhodium‐catalyzed hydrosilylation of bisalkynes with bissilyl hydrides. Monomeric reference compounds 7–10 with similar chromophore components were prepared for comparison. The ratio of donor to acceptor groups is well‐controlled by the precise regiochemistry and nature of the repeat units. The silylene moieties serve as insulating spacers between chromophores. The polymers exhibit light‐harvesting abilities, for which the intensity of the emission enhanced with larger donor‐to‐acceptor ratios. No emission originating from the donors was observed in fluorescence spectra, illustrating that intrachain energy transfer is highly efficient along the polymer chain.
Palladium‐Catalyzed Tandem Reaction of Yne–Propargylic Carbonates with Boronic Acids: A Simple Method for the Synthesis of Fused Aromatic Rings through Allene‐Mediated Electrocyclization
Authors: Wang Feng , Tong Xiaofeng , Cheng Jiang , Zhang Zhaoguo
Published: September 2004

The palladium‐catalyzed tandem reactions of yne–propargylic carbonates with aryl boronic acids, 2‐furyl boronic acid, and 2‐thiopheneboronic acid, followed by 6π‐electrocyclization to give fused ring aromatic products such as naphthalene, benzofuran, and benzothiophene derivatives are realized. Screening of the reaction conditions revealed that the combination of [Pd(PPh3)4] in THF gave the best results in terms of reactivity and product yields in the reaction of yne–propargylic carbonates with phenylboronic acid. The reaction is sensitive toward steric hindrance when substituted phenylboronic acids are emplyed. However, when we take 2‐furyl boronic acid as the organometallic reagent, most substrates perform very well to give benzofuran derivatives. In addition, 2‐thiopheneboronic acid is also a very effective coupling reagent to give bezothiophenes in high yields. A mechanism is proposed that involves the formation of an allenylpalladium complex from Pd0 and propargylic carbonate, followed by insertion of an intramolecular triple bond and the Suzuki coupling reaction, and then electrocyclization.
Anatomy of the nipple and breast ducts revisited
Authors: Love Susan M. , Barsky Sanford H.
Published: September 2004

BACKGROUND

Increasing interest in the intraductal approach to the breast has necessitated revisiting the anatomy of the breast.

METHODS

Using six different complementary in vivo and in vitro approaches, the authors determined the number, distribution, and anatomic properties of the ductal systems of the breast, which extend from the nipple orifices to the terminal duct lobular units.

RESULTS

More than 90% of all nipples examined contained 5–9 ductal orifices, generally arranged as a central group and a peripheral group. Each nipple orifice communicated with a separate, nonanastomosing ductal system, which extended to the terminal duct lobular unit.

CONCLUSIONS

Increased knowledge of the ductal anatomy of the breast and the ability to access the nipple ductal orifices will provide a foundation for the intraductal approach to the breast. Cancer 2004. © 2004 American Cancer Society
Increasing mortality rates of common malignancies in Colombia
Authors: Piñeros Marion , Hernández Gustavo , Bray Freddie
Published: September 2004

BACKGROUND

As a result of a major social and demographic transition, Colombia is currently undergoing major changes in disease‐specific mortality rates, including an increasing burden of cancer death. The current article described some aspects of the evolution of cancer mortality in Colombia and, in particular, highlighted the trends for the most common causes of cancer death in Colombia.

METHODS

Cancer deaths registered in the national mortality database from 1981–1996 were used to obtain age‐standardized mortality rates by gender and site using the world standard population. The estimated annual percentage change was obtained by fitting a simple log‐linear model to the rates in the last decade of recorded data, to gauge recent and near‐future cancer mortality trends.

RESULTS

Between 1987 and 1996, the most common causes of cancer death were gastric carcinoma (17% of all cancer deaths), followed by lung (10.5%), prostate (6.2%), cervical (6%), and colorectal carcinoma (5.4%). There were observed declines in mortality trends noted in both genders for gastric carcinoma. Trends in lung carcinoma appeared to be reaching a plateau among men, but increased among women. There were apparent increases in rates of death from colorectal carcinoma for both genders, and from prostate carcinoma for men. Cervical carcinoma appeared to be increasing moderately.

CONCLUSIONS

The authors reported that mortality rates from the most common malignancies are increasing, indicating that effective strategies for cancer control need to be put into immediate practice. To monitor and evaluate future trends, the provision of high‐quality data also needs to be addressed. Cancer 2004; © 2004 American Cancer Society.
Class I and class II ganglion cells of rabbit retina: Quantitative analysis of dendritic branching patterns
Authors: Famiglietti Edward V.
Published: September 2004

Class I and class II ganglion cells, distinguished from one another in a companion paper, were analyzed in regard to their dendritic branching patterns by determination of: 1) mean “branching density” (BD), 2) “radial branching frequency” (RBF), and 3) “branch length distributions” (BLDs; Famiglietti [ 1992a] J Comp Neurol 324:295–321). Branching density of class II cells exceeded that of class I cells by a factor of two, when compared at the same retinal location, but declined with increasing distance from the visual streak (dvs). A one‐bin difference in RBF between class I and class II cells was not statistically significant. BLDs are scatter‐plots of individual preterminal and terminal branch lengths versus the distances of their origins from the soma. The parameters mp and mt, the slopes of regression lines fitted to the preterminal and terminal BLDs, respectively, were determined; mp, but not mt, was relatively independent of dvs, and was used empirically to determine a boundary value, mp = +5.0, separating “radiate” from “tufted” dendritic branching. Similarity of class I (mp = +8.6 ± 4.6) and class II (mp = +1.4 ± 5.2) cells did not allow a statistically significant separation of the two classes, based upon branching pattern alone; however, mp together with mt easily separated class I cells (mt = −17.8 ± 10.0) and particularly “tufted” class II cells (mt = −16 ± 9.3) from “tufted” class III.1 ganglion cells (Famiglietti, 1992a), with their qualitatively different, more regular branching (mp = +2.1 ± 0.85; mt = +0.65 ±4.9). J. Comp. Neurol. 478:347–358, 2004. © 2004 Wiley‐Liss, Inc.
Cell types, lineage, and architecture of the germinal zone in the adult dentate gyrus
Authors: Seri Bettina , García‐Verdugo José Manuel , Collado‐Morente Lucia , McEwen Bruce S. , Alvarez‐Buylla Arturo
Published: September 2004

New neurons continue to be born in the subgranular zone (SGZ) of the dentate gyrus in the hippocampus of adult mammals, including humans. Previous work has shown that astrocytes function as the progenitors of these new neurons through immature intermediate D cells. In the first part of the present study, we determined the structure of each of these progenitors and how they are organized in three dimensions. Serial‐section reconstructions of the SGZ, using confocal and electron microscopy demonstrate that SGZ astrocytes form baskets that hold clusters of D cells, largely insulating them from the hilus. Two types of glial fibrillary acidic protein–expressing astrocytes (radial and horizontal) and three classes of doublecortin and PSA‐NCAM–positive D cells (D1, D2, D3) were observed. Radial astrocytes appear to interact closely with clusters of D cells forming radial proliferative units. In the second part of this study, we show that retrovirally labeled radial astrocytes give rise to granule neurons. We also used bromodeoxyuridine and [3H]thymidine labeling to study the sequence of appearance of the different D cells after a 7‐day treatment with anti‐mitotics. This analysis, together with retroviral labeling data, suggest that radial astrocytes divide to generate D1 cells, which in turn divide once to form postmitotic D2 cells. D2 cells mature through a D3 stage to form new granule neurons. These observations provide a model of how the germinal zone of the adult hippocampus is organized and suggest a sequence of cellular stages in the generation of new granule neurons. J. Comp. Neurol. 478:359–378, 2004. © 2004 Wiley‐Liss, Inc.
Conditioning lesions enhance axonal regeneration of descending brain neurons in spinal‐cord‐transected larval lamprey
Authors: Zhang Lei , Palmer Ryan , McClellan Andrew D.
Published: September 2004

In larval lamprey, with increasing recovery times after a transection of the rostral spinal cord, there is a gradual recovery of locomotor behavior, and descending brain neurons regenerate their axons for progressively greater distances below the transection site. In the present study, spinal cord “conditioning lesions” (i.e., transections) were performed in the spinal cord at 30% body length (BL; normalized distance from the head) or 50% BL. After various “lesion delay times” (D), a more proximal spinal cord “test lesion” (i.e., transection) was performed at 10% BL, and then, after various recovery times (R), horseradish peroxidase was applied to the spinal cord at 20% BL to determine the extent of axonal regeneration of descending brain neurons. Conditioning lesions at 30% BL, lesion delay times of 2 weeks, and recovery times of 4 weeks (D‐R = 2‐4 group) resulted in a significant enhancement of axonal regeneration for the total numbers of descending brain neurons as well as neurons in certain brain cell groups compared to control animals without conditioning lesions. Experiments with hemiconditioning lesions, which reduce interanimal variability, confirmed that conditioning lesions do significantly enhance axonal regeneration and indicate that axotomy rather than diffusible factors released at the injury site is primarily involved in this enhancement. Results from the present study suggest that conditioning lesions “prime” descending brain neurons via cell body responses and enhance subsequent axonal regeneration, probably by reducing the initial delay and/or increasing the initial rate of axonal outgrowth. J. Comp. Neurol. 478:395–404, 2004. © 2004 Wiley‐Liss, Inc.