bluuebunny/crossref_metadata_2025 huggingface dataset:
Vacuolar hepatopathy in dogs: 336 cases (1993–2005)
Authors: Sepesy Lisa M. , Center Sharon A. , Randolph John F. , Warner Karen L. , Erb Hollis N.
Published: July 2006

Objective—To determine disorders associated with vacuolar hepatopathy (VH), morphologic hepatic and clinicopathologic abnormalities, and affiliation with steroidogenic hormone excess in dogs.

Design—Retrospective case series.

Animals—336 dogs with histologically confirmed moderate or severe VH.

Procedures—Information on signalment, results of diagnostic testing, definitive diagnoses, and exposure to glucocorticoids (ie, exogenous glucocorticoid administration or high endogenous concentrations of steroidogenic hormones) was obtained from medical records. Dogs were grouped by underlying disorder, glucocorticoid exposure, acinar zonal distribution of lesions, and histologic severity.

Results—12 disease groups (neoplastic, acquired hepatobiliary, neurologic, immune-mediated, gastrointestinal tract, renal, infectious, cardiac disease, diabetes mellitus, portosystemic vascular anomaly, adrenal gland dysfunction, and miscellaneous disorders) were identified. There were 186 (55%) dogs with and 150 (45%) dogs without evidence of glucocorticoid exposure. Acinar zonal distribution of hepatic vacuolation and clinicopathologic values did not differ between dogs with and without evidence of glucocorticoid exposure. However, a 3-fold increased likelihood of severe VH was associated with steroidogenic hormone exposure. Of 226 dogs with high serum alkaline phosphatase activity, 102 (45%) had no evidence of glucocorticoid exposure.

Conclusions and Clinical Relevance—Results suggest that neoplasia and congenital or acquired hepatobiliary disease are common in dogs with VH and provide support for the suggestion that VH, high alkaline phosphatase activity, and illness-invoked physiologic stress may be associated. Histologic confirmation of VH should initiate a diagnostic search for a primary disease if glucocorticoid treatment and hyperadrenocorticism are ruled out.
Hemoperitoneum in horses: 67 cases (1989–2004)
Authors: Dechant Julie E. , Nieto Jorge E. , Le Jeune Sarah S.
Published: July 2006

Objective—To evaluate clinical findings, underlying causes, and short-term outcome associated with hemoperitoneum in horses.

Design—Retrospective case series.

Animals—67 horses with hemoperitoneum.

Procedures—Medical records of horses with hemo-peritoneum (excluding postoperative abdominal hemorrhage) from 1989 through 2004 were analyzed. Information obtained included history, signalment, physical examination findings, diagnostic test results, and short-term outcome.

Results—Breed distribution was 28 Thoroughbreds, 13 Arabians, 10 Quarter Horses, 5 Warmbloods, 3 Appaloosas, and 1 each of 8 other breeds. There were 40 mares, 23 geldings, and 4 stallions. Median age was 12 years (range, 1 month to 40 years). Signs of abdominal discomfort were the primary complaint in 79% of horses. Clinical findings included shock (60%) and pale mucous membranes (60%). Median heart rate was 76 beats/min (range, 30 to 216 beats/min), median respiratory rate was 30 breaths/min (range, 8 to 92 breaths/min), median Hct was 31% (range, 10.5% to 73.0%), and total protein concentration was 5.8 g/dL (range, 3.3 to 8.7 g/dL). Cause of hemoperitoneum was attributed to trauma (25.4%), neoplasia (17.9%), uterine artery rupture (13.4%), mesenteric injury (11.9%), disseminated intravascular coagulopathy (6.0%), other causes (3.0%), and idiopathic causes (22.4%). Fifty-one percent of horses survived to hospital discharge, 37% were euthanized, and 12% died. Poor short-term outcome was significantly associated with high respiratory rate and certain underlying causes.

Conclusions and Clinical Relevance—Hemoperitoneum is an infrequent but important cause of abdominal discomfort in horses. Predominant underlying causes were trauma, neoplasia, and idiopathic causes. Identification of underlying cause is important because of its association with outcome.
Comparison of disease severity scoring systems for dairy cattle with acute coliform mastitis
Authors: Wenz John R. , Garry Franklyn B. , Barrington George M.
Published: July 2006

Objective—To compare use of 4 disease severity scoring systems to predict bacteremia (yes vs no) and outcome (survived vs died or culled) in dairy cows with acute coliform mastitis (ACM).

Design—Retrospective cohort study.

Animals—99 dairy cows with ACM.

Procedures—Cows were classified as having mild, moderate, or severe disease with a scoring system based on systemic disease signs alone (systemic severity score [SSS] system), a system based on local disease signs alone (local severity score [LSS] system), and 2 previously described systems based on a combination of local and systemic signs (local-systemic score 1 [LS1] and local-systemic score 2 [LS2] systems). Test performance was calculated to determine whether a severe disease classification could be used to predict bacteremia or outcome.

Results—21%, 53%, 63%, and 38% of cows were classified as having severe disease with the SSS, LSS, LS1, and LS2 systems, respectively. For both bacteremia and outcome, sensitivity was highest for the LS1 system, but specificity and accuracy were highest for the SSS system. Examination of a scatterplot of true-positive rate versus false-positive rate for each of the scoring systems indicated that the SSS and LS2 systems were similar in their ability to correctly identify cows with bacteremia or an adverse outcome.

Conclusions and Clinical Relevance—Results suggest that the SSS scoring system was better for identifying cows with bacteremia or an adverse outcome than was the LSS system and that the LS1 and LS2 systems were intermediate in their discriminatory abilities.
Congenital vulvar deformity in 6 alpacas
Authors: Wilkins Pamela A. , Southwood Louise L. , Bedenice Daniela
Published: July 2006

Case Description—6 female alpacas, ranging in age from < 1 day to > 2 years, were examined because of primary owner complaints related to urogenital malformation.

Clinical Findings—In all instances, the vulva was totally to subtotally imperforate. One neonate had failure of passive transfer of immunity and mild azotemia at the time of initial examination. No additional urogenital malformations were detected in any of the alpacas.

Treatment and Outcome—Vulvoplasty performed via local anesthesia was successful in all alpacas. The neonate with failure of passive transfer received a plasma transfusion. Postsurgical wound management was limited to topically applied medications.

Clinical Relevance—Congenital vulvar deformity in alpacas may result in interference with urine outflow. Neonates with a completely imperforate vulva may be brought to veterinarians for examination on an emergency basis. Less severely affected alpacas may be examined later in life with owner complaints ranging from stranguria or dysuria to urogenital malformation. No other primary abnormalities of the urogenital tract in alpacas have been reported, to the authors' knowledge. Vulvoplasty, performed with local anesthesia, resolves obstructed urine flow. Because it is possible that this condition is heritable, affected alpacas, and possibly their sires and dams, should not be used for breeding.
Prevalence of Salmonella spp in cloacal, fecal, and gastrointestinal mucosal samples from wild North American turtles
Authors: Saelinger Carley A. , Lewbart Gregory A. , Christian Larry S. , Lemons Carol L.
Published: July 2006

Objective—To determine prevalence of Salmonella spp in samples collected from wild North American turtles.

Animals—94 wild North American turtles of 6 species in 2 genera.

Design—Prospective microbiologic study.

Procedures—A convenience sample of wild North Carolina turtles admitted to a veterinary college was evaluated for Salmonella spp by use of standard techniques via microbiologic culture of cloacal swab and fecal samples. Gastrointestinal mucosa samples were also collected at necropsy from turtles that died or were euthanized. Cloacal swab samples were also collected from wild pond turtles for bacteriologic culture. Controls were established by use of wild-type Salmonella Typhimurium LT2.

Results—94 turtles were tested for Salmonella spp; Salmonella spp were not detected in any sample. By use of a pathogen-prevalence and sample-size table, the true prevalence of Salmonella spp was estimated as < 5%.

Conclusions and Clinical Relevance—Results suggested that wild turtles in central North Carolina may not be active shedders or carriers of Salmonella spp. Despite this 0% prevalence of infection, proper hygiene practices should be followed when handling wild turtles.
Tularemia as a cause of fever in a squirrel monkey
Authors: Beckwith Catherine S.
Published: July 2006

Case Description—A 3-year-old female squirrel monkey (Saimiri sciureus sciureus) was examined because of sudden onset of lethargy and fever.

Clinical Findings—On initial examination, the monkey was weak and febrile and had petechiae on both thoracic limbs. Following collection, blood samples were slow to clot. During the next week, the monkey developed anemia and thrombocytopenia; Francisella tularensis was isolated from blood samples.

Treatment and Outcome—Treatment with gentamicin resulted in the monkey's gradual return to health, but inguinal lymphadenopathy developed after drug administration was discontinued. Francisella tularensis was isolated from a fine-needle aspirate of an enlarged lymph node. Treatment with streptomycin resulted in resolution of infection. By use of biochemical and molecular tests, the microbial isolate was characterized as F tularensis subsp holarctica. Results of a microagglutination assay confirmed that the monkey had developed serum antibodies against F tularensis.

Clinical Relevance—With timely diagnosis, treatment of tularemia in the squirrel monkey was successful. Francisella tularensis is the cause of a highly infectious zoonotic disease, and infection with this microorganism is enzootic in wildlife throughout the Northern Hemisphere. Tularemia should be considered in the differential diagnosis of febrile disease in animals of any species. Even limited or indirect exposure of humans or other animals to outdoor environments in which reservoir hosts and arthropod vectors are present can lead to transmission of F tularensis. Francisella tularensis is a class A agent of bioterrorism, and all cases of tularemia (regardless of species) should be reported to public health officials.
Efficient Preparation of New Rhodium‐ and Iridium‐[Bis(oxazolinyl)‐3,5‐dimethylphenyl] Complexes by CH Bond Activation: Applications in Asymmetric Synthesis
Authors: Ito Jun‐ichi , Shiomi Takushi , Nishiyama Hisao
Published: July 2006

The bis(oxazolinyl)‐3,5‐dimethylphenylrhodium and ‐iridium complexes were synthesized in high yields by an efficient CH bond activation method with 4,6‐dimethyl‐1,3‐bis(oxazolinyl)benzene derivatives. The catalytic activity of the complexes was examined for the asymmetric conjugate reduction of (E)‐ethyl 3‐phenylbut‐2‐enoate and the asymmetric reductive aldol reaction of tert‐butyl acrylate and benzaldehyde. It was found that the rhodium complex of 3,5‐dmPhebox showed the higher catalytic activity, whereas the corresponding iridium complexes proved to be less active.
2,3‐Disubstituted Indoles through the Palladium‐Catalyzed Reaction of Aryl Chlorides with o‐Alkynyltrifluoroacetanilides
Authors: Cacchi Sandro , Fabrizi Giancarlo , Goggiamani Antonella
Published: July 2006

2,3‐Disubstituted indoles can be prepared in moderate to excellent yields by reacting readily available o‐alkynyltrifluoroacetanilides with aryl chlorides in MeCN at 120 °C in the presence of Pd2(dba)3 and Xphos.
Subsequent Enzymatic Galactosylation and Sialylation Towards Sialylated Thomsen–Friedenreich Antigen Components
Authors: Kröger Lars , Scudlo Agnes , Thiem Joachim
Published: July 2006

Sialyloligosaccharides of the type Neu5 Acα2‐3Galβ1‐3GalNAc and a range of corresponding motifs play an important role in nature and are found in gangliosides, Lewis type I structures and the sialyl‐Thomsen–Friedenreich antigen occurring in higher animals, viruses, bacteria, protozoa and pathogenic fungi. There is considerable interest to evaluate the significant functionalities of these glycostructures, and here we present a chemoenzymatic approach by a facile synthesis of such motifs. Employing chemoenzymatic methods, several modified Galβ1‐3GalNAc derivatives were synthesized. Modifications were introduced at the stage of the monomeric building blocks prior to formation of the disaccharides by means of four different β‐galactosidases from bovine testes, Bacillus circulans and Xanthomonas manihotis as well as the phosphorylase from Bifidobacterium bifidum. Finally, the modified disaccharide derivatives could be efficiently sialylated using the recombinant trans‐sialidase from Trypanosoma cruzi.
Preparation of a Privileged Silicon‐Stereogenic Silane: Classical versus Kinetic Resolution
Authors: Rendler Sebastian , Auer Gertrud , Keller Manfred , Oestreich Martin
Published: July 2006

The cyclic silicon‐stereogenic silane (SiR)‐5 decorated with three different substituents of distinct steric demand is an exceptionally useful chiral reagent in asymmetric organosilicon chemistry. Several approaches for its large‐scale preparation in optically pure form have been investigated. These hinge upon the resolution of racemic silane rac‐5 which, in turn, is accessible in multi‐gram quantities by a straightforward one‐pot two‐step reaction sequence. For this, a classical as well as a novel kinetic resolution via its diastereomeric silyl ethers derived from enantiopure secondary alcohols as resolving agents has been elaborated: (1) the use of (−)‐menthol [(−)‐7] allowed for a quantitative separation of silyl ethers (SiS)‐10 and (SiR)‐10 by practical fractional crystallization and (2) a diastereoselective copper‐catalyzed dehydrogenative silicon‐oxygen coupling using pyridyl alcohols (S)‐16 or (R)‐16 capable of two‐point binding has been devised and assessed as a novel kinetic resolution strategy for the synthesis of a silane with silicon‐centered chirality. Subsequent stereospecific reductive cleavage of the silicon‐oxygen bond enabled the preparation of (SiR)‐5 and (SiS)‐5 in excellent enantiomeric excesses of up to 99 % ee.
The Dendrimer Effect in Homogeneous Catalysis
Authors: Helms Brett , Fréchet Jean M. J.
Published: July 2006

The immobilization of catalytic groups onto a dendritic support either at the core or at the periphery gives rise to unique properties that affect rates of reaction, substrate activation or selectivity, etc. When advantageous, these properties can be classified as a positive dendrimer effect. Positive dendrimer effects can arise from site isolation, transition state stabilization and/or dielectric effects in the case of core‐modified dendrimers, while peripherally modified dendrimers usually benefit from steric crowding or cooperativity for catalytic residues confined to the surface of the polymer. In this review, the appearance of positive dendrimer effects from the literature will be highlighted as well as prospects for future work in the field.
Iron‐Salen Complexes as Efficient Catalysts in Ring Expansion Reactions of Epoxyalkenes
Authors: Hilt Gerhard , Walter Christian , Bolze Patrick
Published: July 2006

The optimisation of the iron‐catalysed ring expansion reaction of epoxyalkenes was considerably improved when the original phosphine ligand system [FeCl2(dppe)] was altered to include nitrogen‐containing ligand systems. Especially, the very potent class of salen ligands gave the best results in inter‐ and intramolecular ring expansion reactions. With a preformed iron(II)‐salen complex the yields and diastereoselectivities were greatly enhanced and the scope of the reaction could also be enlarged.
Genome‐wide linkage analysis of heroin dependence in Han Chinese: Results from wave one of a multi‐stage study
Authors: Glatt Stephen J. , Su Jessica A. , Zhu Shao C. , Zhang Ruimin , Zhang Bo , Li Jixiang , Yuan Xiaobo , Li Jianhua , Lyons Michael J. , Faraone Stephen V. , Tsuang Ming T.
Published: July 2006

The contribution of genes to the etiology of heroin dependence is greater than for any other illicit drug. The specific genes mediating this effect remain unknown, despite several candidate gene association studies of the condition. Here we report the results of a genome‐wide search for heroin dependence susceptibility loci using multipoint linkage analysis. In phase I, we ascertained 207 independent affected sibling pairs from 202 Han Chinese families from Yunnan Province, China (near Asia's “Golden Triangle”). After data‐cleaning, 194 fully independent sibling pairs (i.e., with no overlapping individuals) from 192 families were genotyped on 404 short tandem‐repeat markers spaced at an average inter‐marker distance of 9 cM. Although none of our findings achieved genome‐wide significance, we found two regions with non‐parametric linkage (NPL) Z‐scores greater than 2.0. An NPL Z‐score of 2.19 (uncorrected P‐value = 0.014) was observed at D4S1644, located at 143.3 cM on chromosomal region 4q31.21. The highest NPL Z‐score of 2.36 (uncorrected P‐value = 0.009) was observed at 53.4 cM on chromosomal region 17q11.2 at marker D17S1880. This is among the first published reports of a genome‐wide linkage analysis of heroin dependence. Forthcoming results from other groups and from two additional waves of ascertainment (one planned, one currently ongoing) for our own study should be able to support or refute the putative susceptibility loci we have identified, after which positional candidate genes can be further evaluated as risk factors for the illness. © 2006 Wiley‐Liss, Inc.
Association study of seven polymorphisms in four serotonin receptor genes on suicide victims
Authors: Videtic Alja , Pungercic Galina , Pajnic Irena Zupanic , Zupanc Tomaz , Balazic Joze , Tomori Martina , Komel Radovan
Published: July 2006

A number of molecular genetic studies have investigated if serotonin (5‐HT) receptor subtypes are involved in the pathogenesis of depression, suicidal behavior, aggression, and impulsive behavior. Existence of many receptor subtypes for a single transmitter permits a great diversity of signaling raising the possibility that they may serve as genetic markers for suicidal behavior. Most previous studies of suicide have analyzed polymorphisms of the receptors 5‐HT1A, 5‐HT1B, 5‐HT2A, fewer have examined 5‐HT1F. We report a study of possible association between the polymorphisms in the 5‐HT receptor genes (1A, 1B, 1F, and 2A) and suicidal behavior on a sample of 226 suicide victims and 225 healthy control subjects. No significant differences in genotype frequency distributions between the suicide victims and healthy control subjects were observed for four polymorphisms; three were not polymorphic. A single polymorphism, C‐1420T in gene 5‐HT2A, showed a slight association with suicide (χ2 = 4.94, df = 2, P = 0.067), but the correlation was not statistically significant. None of the tested genetic variants of serotonin receptors appears to be associated with suicidal behavior in the Slovenian population which has a relatively high suicide rate. © 2006 Wiley‐Liss, Inc.
On‐line estimation of dissolved methane concentration during methanotrophic fermentations
Authors: Yu Yinghao , Ramsay Juliana A. , Ramsay Bruce A.
Published: July 2006

Knowledge of the aqueous phase methane concentration is critical to understanding and controlling process kinetics in methanotrophic bioreactors. Unfortunately since no dissolved methane probe is commercially available, this data must be obtained off‐line by the time‐consuming gas–liquid partition method. In this study we demonstrate how knowledge of the reactor's kLa for oxygen combined with gas phase methane analysis can be used to continuously estimate the aqueous phase concentration of dissolved methane. The on‐line estimation was verified in two reactor systems with greatly different values of k La. In both systems the measured and calculated dissolved methane concentrations were in good agreement although dissolved methane was underestimated in both cases. The utility of this methodology was demonstrated by revealing a possible metabolic bottleneck in the model system. © 2006 Wiley Periodicals, Inc.
Effect of β‐O‐Glucosylation on L‐Ser and L‐Thr Diamides: A Bias toward α‐Helical Conformations
Authors: Corzana Francisco , Busto Jesús H. , Engelsen Søren B. , Jiménez‐Barbero Jesús , Asensio Juan L. , Peregrina Jesús M. , Avenoza A.
Published: July 2006

β‐D‐O‐glucosylation produces a remarkable effect on the peptide backbone of the model peptides derived from serine and threonine. Consequently, this type of glycosylation is responsible for the experimentally observed shift from extended conformations (model peptides) towards the folded conformations (model glycopeptides). The conclusion has been solidly assessed by a combined NMR/MD protocol. Interestingly, the MD (molecular dynamics) results for the glycopeptides point towards the existence of water‐bridging molecules between the sugar and peptide moieties, which could explain the stabilization of the folded conformers in aqueous solution.
Dynamic Kinetic Resolution and Desymmetrization Processes: A Straightforward Methodology for the Enantioselective Synthesis of Piperidines
Authors: Amat Mercedes , Bassas Oriol , Llor Núria , Cantó Margalida , Pérez Maria , Molins Elies , Bosch Joan
Published: July 2006

A straightforward procedure for the synthesis of enantiopure polysubstituted piperidines is reported. It involves the direct generation of chiral non‐racemic oxazolo[3,2‐a]piperidone lactams that already incorporate carbon substituents on the heterocyclic ring and the subsequent removal of the chiral auxiliary. The key step is a cyclocondensation reaction of (R)‐phenylglycinol or other amino alcohols with racemic or prochiral δ‐oxo (di)acid derivatives in highly stereoselective processes involving dynamic kinetic resolution and/or desymmetrization of diastereotopic or enantiotopic ester groups.
Detection of the chirality of Cα‐methylated α‐amino acids with a dynamic helical poly(phenylacetylene) bearing aza‐18‐crown‐6 ether pendants
Authors: Morino Kazuhide , Kaptein Bernard , Yashima Eiji
Published: July 2006

A stereoregular poly(phenylacetylene) bearing the aza‐18‐crown‐6 ether pendants (poly‐1) was found to form a predominantly one‐handed helix upon complexation with optically active Cα‐methylated α‐amino acids and their amide derivatives including typical meteoritic Cα‐methylated α‐amino acids such as Cα‐methyl norvaline and Cα‐methyl valine. The complexes exhibited an induced circular dichroism (ICD) in the UV‐visible region of the polymer backbone. Therefore, poly‐1 can be used as a novel probe for detection of the chirality of Cα‐methylated α‐amino acids. The effect of the enantiomeric excess (ee) of Cα‐methylated α‐amino acids on the helicity induction in poly‐1 was also investigated. Chirality, 2006. © 2006 Wiley‐Liss, Inc.
Asymmetric aza‐Henry reaction of N‐tosyl imine
Authors: Gao Feifeng , Zhu Jiang , Tang Yong , Deng Minzhi , Qian Changtao
Published: July 2006

An efficient stereoselective aza‐Henry reaction of N‐tosyl imine, catalyzed by the coordination of diethylzinc with a chiral semi‐aza‐crown ligand, with moderate to high ee (up to 83%) is reported. Chirality, 2006. © 2006 Wiley‐Liss, Inc.
Ortho–para spin isomers of the protons in the methylene group—Possible implications for protein structure
Authors: Shinitzky Meir , Elitzur Avshalom C.
Published: July 2006

The two hydrogen atoms attached to the carbon in the methylene group are of two different spin configurations, similar to those in the case of water: ortho, where the two proton spins are parallel to each other, and para, where they are antiparallel. The ortho configuration has three degenerate states, while the para configuration is singular, leading to a statistical ratio of these isomers 3:1 ortho/para. Such spin isomers are present in glycine and most chiral amino acids where they may induce broadening of structural zones, a possibility which remains to be assessed. The implications of this neglected possibility could be far‐reaching, in particular with respect to protein structure and the origins of biochirality. Chirality, 2006 © 2006 Wiley‐Liss, Inc.
Long hydrocarbon chains serve as unique molecular features recognized by ventral glomeruli of the rat olfactory bulb
Authors: Ho Sabrina L. , Johnson Brett A. , Leon Michael
Published: July 2006

In an effort to understand mammalian olfactory processing, we have been describing the responses to systematically different odorants in the glomerular layer of the main olfactory bulb of rats. To understand the processing of pure hydrocarbon structures in this system, we used the [14C]2‐deoxyglucose method to determine glomerular responses to a homologous series of alkanes (from six to 16 carbons) that are straight‐chained hydrocarbons without functional groups. We found two rostral regions of activity evoked by these odorants, one lateral and one medial, that were observed to shift ventrally with increasing alkane carbon chain length. Furthermore, we successfully predicted that the longest alkanes with carbon chain length greater than our previous odorant selections would stimulate extremely ventral glomerular regions where no activation had been observed with the hundreds of odorants that we had previously studied. Overlaps in response profiles were observed in the patterns evoked by alkanes and by other aliphatic odorants of corresponding carbon chain length despite possessing different oxygen‐containing functional groups, which demonstrated that hydrocarbon chains could serve as molecular features in the combinatorial coding of odorant information. We found a close and predictable relationship among the molecular properties of odorants, their induced neural activity, and their perceptual similarities. J. Comp. Neurol. 498:16–30, 2006. © 2006 Wiley‐Liss, Inc.
P2X2R purinergic receptor subunit mRNA and protein are expressed by all hypothalamic hypocretin/orexin neurons
Authors: Florenzano Fulvio , Viscomi Maria Teresa , Mercaldo Valentina , Longone Patrizia , Bernardi Giorgio , Bagni Claudia , Molinari Marco , Carrive Pascal
Published: July 2006

Neurophysiologic data suggest that orexin neurons are directly excited by ATP through purinergic receptors (P2XR). Anatomical studies, though reporting P2XR in the hypothalamus, did not describe it in the perifornical hypothalamic area, where orexinergic neurons are located. Here we report the presence of the P2X2R subunit in the rat perifornical hypothalamus and demonstrate that hypothalamic orexin neurons express the P2X2R. Double immunohistochemistry showed that virtually all orexin‐immunoreactive neurons are also P2X2R immunoreactive, whereas 80% of P2X2R‐immunoreactive neurons are also orexin positive. Triple‐labeling experiments, combining fluorescence in situ hybridization for P2X2R mRNA and P2X2R/orexin double immunofluorescence, confirmed these findings. In addition, in situ hybridization demonstrated that P2X2R mRNA is localized in cellular processes of orexinergic neurons. The present data support neurophysiologic findings on ATP modulation of orexinergic function and provide direct evidence that the entire population of orexin neurons expresses a P2XR subtype, namely, P2X2R. Thus, purinergic transmission might intervene in modulating key functions known to be controlled by the orexinergic system, such as feeding behavior and arousal. J. Comp. Neurol. 498:58–67, 2006. © 2006 Wiley‐Liss, Inc.
Electrophoretic mobility of linear and star‐branched DNA in semidilute polymer solutions
Authors: Saha Sourav , Heuer Daniel M. , Archer Lynden A.
Published: July 2006

Electrophoresis of large linear T2 (162 kbp) and 3‐arm star‐branched (NArm = 48.5 kbp) DNA in linear polyacrylamide (LPA) solutions above the overlap concentration c* has been investigated using a fluorescence visualization technique that allows both the conformation and mobility μ of the DNA to be determined. LPA solutions of moderate polydispersity index (PI ∼ 1.7–2.1) and variable polymer molecular weight Mw (0.59–2.05 MDa) are used as the sieving media. In unentangled semidilute solutions (c*<c<ce), we find that the conformational dynamics of linear and star‐branched DNA in electric fields are strikingly different; the former migrating in predominantly U‐ or I‐shaped conformations, depending on electric field strength E, and the latter migrating in a squid‐like profile with the star‐arms outstretched in the direction opposite to E and dragging the branch point through the sieving medium. Despite these visual differences, μ for linear and star‐branched DNA of comparable size are found to be nearly identical in semidilute, unentangled LPA solutions. For LPA concentrations above the entanglement threshold (c>ce), the conformation of migrating linear and star‐shaped DNA manifest only subtle changes from their unentangled solution features, but μ for the stars decreases strongly with increasing LPA concentration and molecular weight, while μ for linear DNA becomes nearly independent of c and Mw. These findings are discussed in the context of current theories for electrophoresis of large polyelectrolytes.
Inflammation stimulates myelination by transplanted oligodendrocyte precursor cells
Authors: Setzu Anna , Lathia Justin D. , Zhao Chao , Wells Karen , Rao Mahendra S. , ffrench‐Constant Charles , Franklin Robin J. M.
Published: July 2006

Inflammation associated with CNS demyelination provides an important stimulus for the activation of endogenous oligodendrocyte precursor cells (OPCs) and subsequent remyelination. This view is largely based on “loss‐of‐function” studies, whereby remyelination is impaired following depletion of inflammatory cells or mediators. However, “gain‐of‐function” approaches, asking whether inflammation directly enhances remyelination, have received less attention. We have addressed this issue using a model in which OPCs transplanted into the adult rat retina myelinate retinal ganglion cell axons around the point of injection. Inflammation (characterized by increased expression of the macrophage marker ED1 and the astrocyte marker GFAP, and the up‐regulation of multiple cytokines) was induced in the retina by the administration of the TLR‐2 ligand zymosan. Myelination, revealed by MBP+ myelin sheaths, was substantially increased when OPCs were injected into the inflamed retina compared to that achieved following transplantation into the normal, noninflamed retina. Our results have important implications for the development of immunomodulatory treatments for acute demyelinating disease and for the therapeutic creation of proremyelination environments in chronic demyelinating disease. © 2006 Wiley‐Liss, Inc.
Regulation of the astrocyte resting membrane potential by cyclic AMP and protein kinase A
Authors: Bolton Sally , Greenwood Kirsty , Hamilton Nicola , Butt Arthur M.
Published: July 2006

The factors regulating astroglial resting membrane potential (RMP) are unresolved. Here, we have examined developmental, morphological, and intracellular factors that may regulate the RMP in astrocytes of isolated intact optic nerves of rats and mice aged postnatal day (P3) to adult. The astroglial RMP ranged from −25 to −85 mV, independent of age and morphological phenotype. There was a developmental negative shift in the astroglial RMP from a non‐Gaussian distribution in perinatal nerves, to a bimodal distribution of RMPs after P15, with peaks at −52 and −74 mV in adults. Blockade of Kir with 100 μM BaCl2 significantly depolarized the RMP to −30 mV; the RMP was unaffected by TEA or agents that modulated ATP‐sensitive potassium channels. Raising intracellular cyclic AMP (cAMP) with dbcAMP or forskolin induced a significant hyperpolarization by ∼15 mV, whereas inhibition of cAMP‐dependent protein kinase (PKA) depolarized the astroglial RMP to −40 mV. The hyperpolarizing action of dbcAMP was blocked by 100 μM BaCl2. The effects of BaCl2 indicate that the developmental negative shift in the RMP and the cAMP‐mediated hyperpolarization were dependent on Kir. This study provides evidence that the heterogeneous RMP of mature astrocytes is regulated by cAMP and PKA signaling. © 2006 Wiley‐Liss, Inc.
Treatment of cremaster synkinesias with botulinum toxin A: A video case report
Authors: Ritter Martin A. , Frese Achim , Dziewas Rainer , Knecht Stefan , Evers Stefan
Published: July 2006

Synkinesias secondary to nerve lesions and aberrant re‐innervation are well‐known phenomena especially after lesions of the facial nerve. Synkinesias can successfully be treated with botulinum toxin A (BTx A). Synkinesias of the cremaster muscle have not been described or treated to date. We present the case of a 62‐year‐old man who developed synkinesias of both cremaster muscles after extensive laparatomy for esophageal cancer. Treatment of synkinesias with various oral medications had been unsuccessful. Electromyography‐guided injections of BTx A in both cremaster muscles (15 MU on the right and 10 on the left) led to significant symptom relief for an average of 8 weeks. We present the case including pre‐ and posttreatment video clips. © 2006 Movement Disorder Society
Reduced potency after refrigerated storage of botulitum toxin A: Human extensor digitorum brevis muscle study
Authors: Paik Nam‐Jong , Seo Kyle , Eun Hee Chul
Published: July 2006

To determine whether the potency of botulinum toxin A (BTA) decreases after being reconstituted with normal saline and stored in refrigerator, we injected one side of the extensor digitorum brevis muscle with 2.5 units of botulinum toxin A that had been immediately reconstituted with saline, and the contralateral side with identical material that had been reconstituted and stored in a refrigerator for preselected periods (1, 2, and 4 weeks) in 32 healthy volunteers. Mean compound muscle action potential amplitudes expressed as a percentage of the baseline amplitude were more reduced in sides injected with immediately reconstituted BTA than in sides injected with BTA stored for 1 week or more (P < 0.05). No bacterial growth was observed in any stored BTA samples. Storage of reconstituted BTA at low temperatures may affect the potency of the toxin. Therefore, the use of BTA after refrigerated storage is not recommended. © 2006 Movement Disorder Society
Recurrent dystonia in homocystinuria: A metabolic pathogenesis
Authors: Sinclair Alex J. , Barling Lucy , Nightingale Simon
Published: July 2006

Dystonia complicating homocystinuria is extremely rare in the absence of thromboembolic disease. We report a unique case of recurrent dystonia in a patient with homocystinuria secondary to pyridoxine‐unresponsive cystathionine β‐synthase deficiency. Brain MRI was normal. Two biochemical markers for homocystinuria, homocystine and methionine, were markedly elevated during periods when our patient manifested dystonia. These findings suggest that accumulation of sulfur‐containing amino acids may contribute to the pathophysiology of dystonia in patients with homocystinuria. © 2006 Movement Disorder Society
Effects of tyramine administration in Parkinson's disease patients treated with selective MAO‐B inhibitor rasagiline
Authors: deMarcaida J. Antonelle , Schwid Steven R. , White William B. , Blindauer Karen , Fahn Stanley , Kieburtz Karl , Stern Matthew , Shoulson Ira
Published: July 2006

Rasagiline is a novel, potent, and selective MAO‐B inhibitor shown to be effective for Parkinson's disease. Traditional nonselective MAO inhibitors have been associated with dietary tyramine interactions that can induce hypertensive reactions. To test safety, tyramine challenges (50–75 mg) were performed in 72 rasagiline‐treated and 38 placebo‐treated Parkinson's disease (PD) patients at the end of two double‐blind placebo‐controlled trials of rasagiline. An abnormal pressor response was prespecified as three consecutive measurements of systolic blood pressure (BP) increases of ≥ 30 mm Hg and/or bradycardia of < 40 beats/min. In the first study involving 55 patients with early PD on rasagiline monotherapy, no patients randomized to rasagiline (1 mg/2 mg; n = 38) or placebo (n = 17) developed systolic BP (SBP) or heart rate changes indicative of a tyramine reaction. In the second trial involving 55 levodopa‐treated patients, 3 of 22 subjects on rasagiline 0.5 mg/day and 1 of 21 subjects on placebo developed asymptomatic, self‐limiting SBP elevations ≥ 30 mm Hg on three measurements. No subject on 1 mg/day rasagiline (0/12) experienced significant BP or heart rate changes following tyramine ingestion. These data demonstrate that rasagiline 0.5 to 2 mg daily is not associated with clinically significant tyramine reactions and can be used as monotherapy or adjunct to levodopa in PD patients without specific dietary tyramine restriction. © 2006 Movement Disorder Society
Elevated levels of amyloid precursor protein in muscle of patients with amyotrophic lateral sclerosis and a mouse model of the disease
Authors: Koistinen Hannu , Prinjha Rab , Soden Peter , Harper Alex , Banner Steven J. , Pradat Pierre‐François , Loeffler Jean‐Philippe , Dingwall Colin
Published: July 2006

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease defined by motor neuron loss. Transgenic mouse models show features that closely mimic those seen in the clinical situation, reflected in the molecular changes observed in mouse models and in tissues from patients. We report a dramatic increase in the expression of amyloid precursor protein (APP) in the hindlimb muscles, but not the spinal cord of the G93A transgenic mouse model, significantly before the appearance of clinical abnormalities. APP levels were unchanged in nontransgenic mice and in mice overexpressing human wild‐type Cu/Zn‐dependent superoxide dismutase 1 (SOD1). Preliminary results indicate a similar change in APP expression in human deltoid muscle samples from ALS patients compared with age‐matched controls. The inhibitory role of APP in innervation at the neuromuscular junction and increased expression in inclusion‐body myositis suggest that presymptomatic upregulation of APP may be consistent with a potential role for APP in ALS pathology. Muscle Nerve, 2006
Down‐regulation of p21 (CDKN1A/CIP1) is inversely associated with microsatellite instability and CpG island methylator phenotype (CIMP) in colorectal cancer
Authors: Ogino S , Kawasaki T , Kirkner GJ , Ogawa A , Dorfman I , Loda M , Fuchs CS
Published: July 2006

p21 (CDKN1A/CIP1/WAF1), one of the cyclin‐dependent kinase inhibitors, plays a key role in regulating the cell cycle and is transcriptionally regulated by p53. Down‐regulation of p21 is caused by TP53 mutations in colorectal cancer. CpG island methylator phenotype (CIMP) appears to be a distinct subtype of colorectal cancer with concordant methylation of multiple gene promoters and is associated with a high degree of microsatellite instability (MSI‐H) and BRAF mutations. However, no study to date has evaluated the relationship between p21 expression and CIMP in colorectal cancer. The purpose of this study was to examine the inter‐relationships between p21, p53, CIMP, MSI and KRAS/BRAF status in colorectal cancer. We utilized 737 relatively unbiased samples of colorectal cancers from two large prospective cohort studies. Using quantitative real‐time PCR (MethyLight), we measured DNA methylation in five CIMP‐specific gene promoters [CACNA1G, CDKN2A (p16/INK4A), CRABP1, MLH1 and NEUROG1]. CIMP‐high (≥4/5 methylated promoters) was diagnosed in 118 (16%) of the 737 tumours. We also assessed expression of p21 and p53 by immunohistochemistry. Among the 737 tumours, 371 (50%) showed p21 loss. Both p21 loss and p53 positivity were inversely associated with CIMP‐high, MSI‐H and BRAF mutations. The associations of p21 with these molecular features were still present after tumours were stratified by p53 status. In contrast, the associations of p53 positivity with the molecular features were no longer present after tumours were stratified by p21 status. When CIMP‐high and non‐CIMP‐high tumours were stratified by MSI or KRAS/BRAF status, CIMP‐high and MSI‐H (but not BRAF mutations) were still inversely associated with p21 loss. In conclusion, down‐regulation of p21 is inversely correlated with CIMP‐high and MSI‐H in colorectal cancer, independent of TP53 and BRAF status. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Radiotherapy in the multimodal treatment of extrarenal extracranial malignant rhabdoid tumors
Authors: Puri Dev R. , Meyers Paul A. , Kraus Dennis H. , LaQuaglia Michael P. , Wexler Leonard H. , Wolden Suzanne L.
Published: July 2006

Extrarenal extracranial malignant rhabdoid tumors (MRT) are extremely rare and typically lethal. No consensus exists on an optimal treatment approach, and, in particular, the role of radiation therapy (RT) is poorly defined. We report on three children who underwent multimodality treatment including surgery, chemotherapy (CMT), and RT. Two of these patients are alive and without evidence of disease 6½ and 7 years after diagnosis and one has expired. Our limited experience suggests that RT in the setting of CMT and surgery has the potential to prolong survival with acceptable toxicity, but outcomes are inconsistent and further study is necessary. Pediatr Blood Cancer 2008;50:167–169. © 2006 Wiley‐Liss, Inc.
Substitution of oral and intravenous thioguanine for mercaptopurine in a treatment regimen for children with standard risk acute lymphoblastic leukemia: A collaborative Children's Oncology Group/National Cancer Institute pilot trial (CCG‐1942)
Authors: Jacobs Shana S. , Stork Linda C. , Bostrom Bruce C. , Hutchinson Ray , Holcenberg John , Reaman Gregory H. , Erdmann Gary , Franklin Janet , Neglia Joseph P. , Steinberg Seth M. , Balis Frank M. , Adamson Peter C.
Published: July 2006

Background

Although mercaptopurine (MP) is conventionally used to treat childhood acute lymphoblastic leukemia (ALL), thioguanine (TG) is a more potent thiopurine in vitro and, when administered orally to patients, achieves cytotoxic drug concentrations in the cerebrospinal fluid (CSF). We performed a pilot study incorporating oral and 24‐hr continuous IV infusion (CIVI) TG in children with newly diagnosed standard‐risk ALL.

Procedure

Children with newly diagnosed standard‐risk ALL (age 1–10 years, WBC < 50 k) were eligible. Multi‐agent chemotherapy was patterned after the Children's Cancer Group (CCG) 105 trial, with the addition of CIVI‐TG (480 mg/m2) during consolidation, interim maintenance and maintenance, and substitution of oral TG (60 mg/m2/day) for oral MP during maintenance.

Results

Fifty‐eight patients (31 female), median age 4.3 years, were enrolled. At 8 years, the relapse‐free and overall survival probabilities were 83% and 88%. There were no CNS relapses. Six patients (five males) experienced reversible veno‐occlusive disease (VOD) while receiving oral TG, and the study was amended to discontinue TG, changing all patients to oral MP. Red cell TG nucleotide concentrations during oral TG averaged 95 ng (570 pmol)/8 × 108 RBC, greater than concentrations reported with oral MP.

Conclusion

Although the absence of CNS relapses in this pilot study suggests that TG may contribute to the prevention of CNS recurrences, the development of VOD negatively impacts the risk:benefit ratio of substituting TG for MP. Pediatr Blood Cancer 2007;49:250–255. © 2006 Wiley‐Liss, Inc.
Laboratory and field evaluations of rhodojaponin‐III against the imported cabbage worm Pieris rapae (L.) (Lepidoptera: Pieridae)
Authors: Zhong Guohua , Liu Jingxiang , Weng Qunfang , Hu Meiying , Luo Jianjun
Published: July 2006

The activity of rhodojaponin‐III (R‐III), a grayanoid diterpene compound isolated from Rhododendron molle G. Don flowers, was determined under laboratory and field conditions as an antifeedant, stomach poison, contact toxicant and insect growth inhibitor against Pieris rapae (L.) larvae. The median antifeedant concentration (AFC50) values in no‐choice leaf disc tests were 1.16 and 15.85 mg L−1 at 24 h after treatment when tested against third and fifth instars respectively. The median lethal concentration (LC50) values in leaf disc tests were 2.84 and 9.53 mg L−1 at 96 h after treatment against third and fifth instars respectively. R‐III showed an almost 30 times higher contact toxicity against third instars than for fifth instars, and the median lethal dose (LD50) values for topical application were 1.18 and 34.09 mg kg−1 at 72 h after treatment respectively. R‐III disrupted the development of larvae to pupae or adults with median concentration for inhibiting growth (IC50) values of only 1.36 mg L−1 for third instars and 11.28 mg L−1 for fifth instars. In field trials, a greater than 80% reduction in the adjusted larval numbers was obtained against P. rapae 14 days after treatment when Rhodo 0.1% EC, a commercial botanical insecticide based on R‐III, was applied at both 937.5 and 625 mL ha−1. These results suggest that further research to develop R‐III, and extracts from R. molle, as biorational pesticides or as lead compounds for integrated pest management deserve consideration. Copyright © 2006 Society of Chemical Industry
Theoretical investigation of the chain length effects on the NMR chemical shifts of oligomers
Authors: d'Antuono Philippe , Botek Edith , Champagne Benoît
Published: July 2006

Chain length effects on the 1H and 13C NMR chemical shifts have been theoretically investigated for increasingly large oligomers of isotactic and syndiotactic polypropylene and poly(vinyl chloride). Chains ranging from the dimer to the octamer and decamer have been considered for polypropylene and poly(vinyl chloride), respectively. Helical structures displaying successive TG backbone conformations represent the isotactic chains, whereas syndiotactic chains are considered to be all‐trans. The calculations are carried out by employing density functional theory (DFT) with the B3LYP exchange‐correlation functional and the 6‐311+G(2d,p) basis set. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
DFT study of bare and dye‐sensitized TiO2 clusters and nanocrystals
Authors: Lundqvist Maria J. , Nilsing Mattias , Persson Petter , Lunell Sten
Published: July 2006

Structural and electronic properties of bare and dye‐sensitized TiO2 clusters and nanoparticles with sizes of ≤2 nm have been studied by density functional theory (DFT) calculations. Starting from truncated bulk lattice structures, the degree of structural reorganization, including the formation of TiO surface species, of bare TiO2 anatase nanocrystals, is found to be sensitive to the quality of the computational method. The electronic structures of optimized 1–2 nm nanoparticles show well‐developed band structures with essentially no electronic bandgap defect states. Significant bandgap broadening due to quantum size effects is observed as the size of the nanocrystals is reduced from 2 nm to 1 nm in diameter, but further bandgap widening is limited by increasingly severe competing surface defect sites as the particles become smaller than ∼1 nm in diameter. The applicability of the TiO2 nanocrystals in modeling the electronic structure and electronic coupling at dye‐sensitized TiO2 nanocrystal interfaces has been investigated by attachment of pyridine to one of the nanoparticle models via phosphonic or carboxylic acid anchor groups. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006