bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of using gene expression in mononuclear cells as a marker for hepatic cholesterol metabolism
Authors: Aggarwal Dimple , Freake Hedley C , Soliman Ghada A , Dutta Amrita , Fernandez Maria-Luz
Published: August 2006

HMG-CoA reductase and the LDL receptor are ubiquitously expressed in major tissues. Since the liver plays a major role in regulating circulating LDL, it is usually of interest to measure the effects of drug or dietary interventions on these proteins in liver. In humans, peripheral blood mononuclear cells have been used as a surrogate for liver to assess regulation of these genes, although there is concern regarding the validity of this approach. The purpose of this study was to evaluate the relationship between liver and mononuclear cell expression of HMG-CoA reductase and the LDL receptor in guinea pigs, a well established model for human cholesterol and lipoprotein metabolism. We extracted RNA from liver and mononuclear cells of guinea pigs from a previous study where the effects of rapamycin, an immunosuppresant drug used for transplant patients, on lipid metabolism were evaluated. Guinea pigs were assigned to three different diets containing the same amount of fat (15 g/100 g) and cholesterol (0.08 g/100 g) for a period of 3 weeks. The only difference among diets was the concentration of rapamycin: 0, 0.0028 or 0.028 g/100 g. There were no differences in plasma LDL cholesterol (LDL-C) among groups. Values were 78.4 ± 14.3, 65.8 ± 17.2 and 68.4 ± 45.4 mg/dL (P > 0.05) for guinea pigs treated with 0, low or high doses of rapamycin, respectively. The mRNA abundance for the LDL receptor and HMG-CoA reductase was measured both in liver (n = 30) and mononuclear cells (n = 22) using reverse transcriptase PCR. In agreement with the finding of no changes in plasma LDL-C, there were also no differences for the expression of HMG-CoA reductase or the LDL receptor among groups. However, a positive correlation was found between liver and mononuclear cells for both HMG-CoA reductase (r = 0.613, P < 0.01) and the LDL receptor (r = 0.622, P < 0.01). These correlations suggest that monocytes can be used in humans as an index for liver to assess diet and drug effects on the expression of HMG-CoA reductase and the LDL receptor.
Health related quality of life trajectories and predictors following coronary artery bypass surgery
Authors: Le Grande Michael R , Elliott Peter C , Murphy Barbara M , Worcester Marian UC , Higgins Rosemary O , Ernest Christine S , Goble Alan J
Published: August 2006

Background

Many studies have demonstrated that health related quality of life (HRQoL) improves, on average, after coronary artery bypass graft surgery (CABGS). However, this average improvement may not be realized for all patients, and it is possible that there are two or more distinctive groups with different, possibly non-linear, trajectories of change over time. Furthermore, little is known about the predictors that are associated with these possible HRQoL trajectories after CABGS.

Methods

182 patients listed for elective CABGS at The Royal Melbourne Hospital completed a postal battery of questionnaires which included the Short-Form-36 (SF-36), Profile of Mood States (POMS) and the Everyday Functioning Questionnaire (EFQ). These data were collected on average a month before surgery, and at two months and six months after surgery. Socio-demographic and medical characteristics prior to surgery, as well as surgical and post-surgical complications and symptoms were also assessed. Growth curve and growth mixture modelling were used to identify trajectories of HRQoL.

Results

For both the physical component summary scale (PCS) and the mental component summary scale (MCS) of the SF-36, two groups of patients with distinct trajectories of HRQoL following surgery could be identified (improvers and non-improvers). A series of logistic regression analyses identified different predictors of group membership for PCS and MCS trajectories. For the PCS the most significant predictors of non-improver membership were lower scores on POMS vigor-activity and higher New York Heart Association dyspnoea class; for the MCS the most significant predictors of non-improver membership were higher scores on POMS depression-dejection and manual occupation.

Conclusion

It is incorrect to assume that HRQoL will improve in a linear fashion for all patients following CABGS. Nor was there support for a single response trajectory. It is important to identify characteristics of each patient, and those post-operative symptoms that could be possible targets for intervention to improve HRQoL outcomes.
Evaluating preference weights for the Asthma Symptom Utility Index (ASUI) across countries
Authors: Flood Emuella M , Cock Erwin De , Mörk Ann-Christin , Revicki Dennis A
Published: August 2006

Background

The Asthma Symptom Utility Index (ASUI) is a preference-based outcome measure used in US clinical trials and cost-effectiveness studies for asthma. This study evaluated ASUI preference weights in Europe to determine whether the multi-attribute utility function, based on preferences from a US population, is generalizable across countries.

Methods

Data were collected from ninety asthma patients from Italy, France, and the United Kingdom using the Asthma Control Questionnaire, the Asthma Quality of Life Questionnaire, and the ASUI. Subjects rated their preferences for 10 asthma health states using a visual analogue scale (VAS) and a standard gamble (SG) interview.

Results

All multi-symptom states showed statistically significant differences (p < 0.001) between countries in mean VAS scores. Mean SG utility scores between the US and France and the US and Italy demonstrated statistically significant differences (p < 0.001) for three states: severe wheeze; moderate cough and wheeze; and moderate cough and dyspnea. Because of these differences, the multi-attribute utility functions derived within countries were somewhat different. Despite these differences, country-specific algorithms captured a similar rank ordering of patients by disease severity, were strongly correlated (r = 0.971 to 0.995), and demonstrated similar relationships with symptom and AQLQ scores.

Conclusion

Results of this study suggest that the ASUI may be a complementary patient-reported outcome for clinical studies and may be useful for applications in cost-effectiveness studies comparing different asthma treatments.
Tactile-like corpuscles in gastric mucosa: a case report
Authors: Salim Sadia , Liu Beiqing , Mahmoodi Mandana , Asad Haider , Hou Steve J
Published: August 2006

Background

The presence of tactile corpuscle-like structures in Schwannomas, Neurofibromas and Neuroid Intradermal Melanocytic Nevi is well-documented. We report a case describing the presence of such structures in the lamina propria of grossly normal gastric mucosa.

Case presentation

A 30 year-old male underwent esophagogastrectomy for carcinoma. Examination of hematoxylin and eosin stained sections reveal tactile corpuscle-like structures in the mucosa adjacent to the main tumor mass.

Conclusion

This is a rare phenomenon and a literature search revealed only one paper describing such structures in the benign colonic mucosa of a colectomy done for carcinoma. We did not come across any cases in the literature describing such structures in gastrointestinal specimen resected for reasons other than carcinoma. To our knowledge this would be the first case reporting the existence of tactile corpuscles-like structures in gastric mucosa.
Inhibition of HIV Env binding to cellular receptors by monoclonal antibody 2G12 as probed by Fc-tagged gp120
Authors: Binley James M , Ngo-Abdalla Stacie , Moore Penny , Bobardt Michael , Chatterji Udayan , Gallay Philippe , Burton Dennis R , Wilson Ian A , Elder John H , de Parseval Aymeric
Published: August 2006

During natural HIV infection, an array of host receptors are thought to influence virus attachment and the kinetics of infection. In this study, to probe the interactions of HIV envelope (Env) with various receptors, we assessed the inhibitory properties of various anti-Env monoclonal antibodies (mAbs) in binding assays. To assist in detecting Env in attachment assays, we generated Fc fusions of full-length wild-type gp120 and several variable loop-deleted gp120s. Through investigation of the inhibition of Env binding to cell lines expressing CD4, CCR5, DC-SIGN, syndecans or combinations thereof, we found that the broadly neutralizing mAb, 2G12, directed to a unique carbohydrate epitope of gp120, inhibited Env-CCR5 binding, partially inhibited Env-DC-SIGN binding, but had no effect on Env-syndecan association. Furthermore, 2G12 inhibited Env attachment to primary monocyte-derived dendritic cells, that expressed CD4 and CCR5 primary HIV receptors, as well as DC-SIGN, and suggested that the dual activities of 2G12 could be valuablein vivofor inhibiting initial virus dissemination and propagation.
Mixing patterns and the spread of close-contact infectious diseases
Authors: Edmunds WJ , Kafatos G , Wallinga J , Mossong JR
Published: August 2006

Surprisingly little is known regarding the human mixing patterns relevant to the spread of close-contact infections, such as measles, influenza and meningococcal disease. This study aims to estimate the number of partnerships that individuals make, their stability and the degree to which mixing is assortative with respect to age. We defined four levels of putative at-risk events from casual (physical contact without conversation) to intimate (contact of a sexual nature), and asked university student volunteers to record details on those they contacted at these levels on three separate days. We found that intimate contacts are stable over short time periods whereas there was no evidence of repeat casual contacts with the same individuals. The contacts were increasingly assortative as intimacy increased. Such information will aid the development and parameterisation of models of close contact diseases, and may have direct use in outbreak investigations.
A method for exposing rodents to resuspended particles using whole-body plethysmography
Authors: Wichers Lindsay B , Ledbetter Allen D , McGee John K , Kellogg Robert B , Rowan William H , Nolan Julianne P , Costa Daniel L , Watkinson William P
Published: August 2006

Background

Epidemiological studies have reported increased risks of cardiopulmonary-related hospitalization and death in association with exposure to elevated levels of particulate matter (PM) across a wide range of urban areas. In response to these findings, researchers have conducted animal inhalation exposures aimed at reproducing the observed toxicologic effects. However, it is technically difficult to quantitate the actual amount of PM delivered to the lung in such studies, and dose is frequently estimated using default respiration parameters. Consequently, the interpretation of PM-induced effects in rodents exposed via whole-body inhalation is often compromised by the inability to determine deposited dose. To address this problem, we have developed an exposure system that merges the generation of dry, aerosolized particles with whole-body plethysmography (WBP), thus permitting inhalation exposures in the unrestrained rat while simultaneously obtaining data on pulmonary function.

Results

This system was validated using an oil combustion-derived particle (HP12) at three nominal concentrations (3, 12, and 13 mg/m3) for four consecutive exposure days (6 hr/day); a single 6-hour exposure to 13 mg/m3 of HP12 was also conducted. These results demonstrated that the system was both reliable and consistent over these exposure protocols, achieving average concentrations that were within 10% of the targeted concentration. In-line filters located on the exhaust outlets of individual WBP chambers showed relative agreement in HP12 mass for each day and were not statistically different when compared to one another (p = 0.16). Temperatures and relative humidities were also similar between chambers during PM and air exposures. Finally, detailed composition analyses of both HP12 filter and bulk samples showed that grinding and aerosolization did not change particle chemistry.

Conclusion

The results of this study demonstrate that it is possible to expose rodents to resuspended, dry PM via whole-body inhalation while these animals are maintained in WBP chambers. This new methodology should significantly improve the ability to assess dosimetry under minimally stressful exposure conditions.
Codon usage patterns in Nematoda: analysis based on over 25 million codons in thirty-two species
Authors: Mitreva Makedonka , Wendl Michael C , Martin John , Wylie Todd , Yin Yong , Larson Allan , Parkinson John , Waterston Robert H , McCarter James P
Published: August 2006

Background

Codon usage has direct utility in molecular characterization of species and is also a marker for molecular evolution. To understand codon usage within the diverse phylum Nematoda, we analyzed a total of 265,494 expressed sequence tags (ESTs) from 30 nematode species. The full genomes of Caenorhabditis elegans and C. briggsae were also examined. A total of 25,871,325 codons were analyzed and a comprehensive codon usage table for all species was generated. This is the first codon usage table available for 24 of these organisms.

Results

Codon usage similarity in Nematoda usually persists over the breadth of a genus but then rapidly diminishes even within each clade. Globodera, Meloidogyne, Pristionchus, and Strongyloides have the most highly derived patterns of codon usage. The major factor affecting differences in codon usage between species is the coding sequence GC content, which varies in nematodes from 32% to 51%. Coding GC content (measured as GC3) also explains much of the observed variation in the effective number of codons (R = 0.70), which is a measure of codon bias, and it even accounts for differences in amino acid frequency. Codon usage is also affected by neighboring nucleotides (N1 context). Coding GC content correlates strongly with estimated noncoding genomic GC content (R = 0.92). On examining abundant clusters in five species, candidate optimal codons were identified that may be preferred in highly expressed transcripts.

Conclusion

Evolutionary models indicate that total genomic GC content, probably the product of directional mutation pressure, drives codon usage rather than the converse, a conclusion that is supported by examination of nematode genomes.
Quantitative magnetic resonance and SPECT imaging for macrophage tissue migration and nanoformulated drug delivery
Authors: Gorantla Santhi , Dou Huanyu , Boska Michael , Destache Chris J , Nelson Jay , Poluektova Larisa , Rabinow Barett E , Gendelman Howard E , Mosley R Lee
Published: August 2006

We posit that the same mononuclear phagocytes (MP) [bone marrow (BM) and blood monocytes, tissue macrophages, microglia, and dendritic cells] which serve as targets, reservoirs, and vehicles for HIV dissemination, can be used as vehicles for antiretroviral therapy (ART). Toward this end, BM macrophages (BMM) were used as carriers for nanoparticle-formulated indinavir (NP-IDV), and the cell distribution was monitored by single photon emission computed tomography (SPECT), transverse relation time (T2)∗ weighted magnetic resonance imaging (MRI), histology, and γ-scintillation spectrometry. BMM labeled with super paramagnetic iron oxide and/or 111 indium oxine were infused i.v. into naïve mice. During the first 7 h, greater than 86% of cell label was recorded within the lungs. On Days 1, 3, 5, and 7, less than 10% of BMM were in lungs, and 74–81% and 13–18% were in liver and spleen, respectively. On a tissue volume basis, as determined by SPECT and MRI, BMM densities in spleen and liver were significantly greater than other tissues. Migration into the lymph nodes on Days 1 and 7 accounted for 1.5–2% of the total BMM. Adoptive transfer of BMM loaded with NP-IDV produced drug levels in lymphoid and nonlymphoid tissues that exceeded reported therapeutic concentrations by 200- to 350-fold on Day 1 and remained in excess of 100- to 300-fold on Day 14. These data show real-time kinetics and destinations of macrophage trafficking and demonstrate the feasibility of monitoring macrophage-based, nanoformulated ART.
HIV accomplices and adversaries in macrophage infection
Authors: Wahl Sharon M , Greenwell-Wild Teresa , Vázquez Nancy
Published: August 2006

Cell surface and intracellular proteins in macrophages influence various steps in the life cycle of lentiviruses. Characterization of these restriction and/or cofactors is essential to understanding how macrophages become unwitting HIV hosts and in fact, can coexist with a heavy viral burden. Although many of the cellular pathways co-opted by HIV in macrophages mimic those seen in CD4+ T cells, emerging evidence reveals cellular constituents of the macrophage, which may be uniquely usurped by HIV. For example, in addition to CD4 and CCR5, membrane annexin II facilitates early steps in infection of macrophages, but not in T cells. Blockade of this pathway effectively diminishes macrophage infection. Viral binding engages a macrophage-centric signaling pathway and a transcriptional profile, including genes such as p21, which benefit the virus. Once inside the cell, multiple host cell molecules are engaged to facilitate virus replication and assembly. Although the macrophage is an enabler, it also possesses innate antiviral mechanisms, including apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3) family DNA-editing enzymes to inhibit replication of HIV. Differential expression of these enzymes, which are largely neutralized by HIV to protect its rebirth, is associated with resistance or susceptibility to the virus. Higher levels of the cytidine deaminases endow potential HIV targets with a viral shield, and IFN-α, a natural inducer of macrophage APOBEC expression, renders macrophages tougher combatants to HIV infection. These and other manipulatable pathways may give the macrophage a fighting chance in its battle against the virus.
Detection of Aberrant Methylation of Four Genes in Plasma DNA for the Detection of Breast Cancer
Authors: Hoque Mohammad O. , Feng Qinghua , Toure Papa , Dem Amadou , Critchlow Cathy W. , Hawes Stephen E. , Wood Troy , Jeronimo Carmen , Rosenbaum Eli , Stern Joshua , Yu Mujun , Trink Barry , Kiviat Nancy B. , Sidransky David
Published: August 2006

Purpose

Novel approaches to breast cancer screening are necessary, especially in the developing world where mammography is not feasible. In this study, we explored the hypothesis that blood-based biomarkers have potential for biomarkers for breast cancer.

Patients and Methods

We first determined the frequency of aberrant methylation of four candidate genes (APC, GSTP1, Rassf1A, and RARβ2) in primary breast cancer tissues from West African women with predominantly advanced cancers. We used a high-throughput DNA methylation assay (quantitative methylation-specific polymerase chain reaction) to examine plasma from 93 women with breast cancer and 76 controls for the presence of four methylated genes. Samples were randomly divided evenly into training and validation data sets. Cutoff values for gene positivity of the plasma-based assay and the gene panel were determined by receiver operating characteristic curves in the training data set and subsequently evaluated as a screening tool in the validation data set.

Results

Methylation of at least one gene resulted in a sensitivity of 62% and a specificity of 87%. Moreover, the assay successfully detected 33% (eight of 24) of early-stage tumors.

Conclusion

These data suggest that epigenetic markers in plasma may be of interest for detection of breast cancer. Identification of additional breast cancer specific methylated genes with higher prevalence in early stage cancers would improve this approach.
Genotype-Phenotype Comparison of German MLH1 and MSH2 Mutation Carriers Clinically Affected With Lynch Syndrome: A Report by the German HNPCC Consortium
Authors: Goecke Timm , Schulmann Karsten , Engel Christoph , Holinski-Feder Elke , Pagenstecher Constanze , Schackert Hans K. , Kloor Matthias , Kunstmann Erdmute , Vogelsang Holger , Keller Gisela , Dietmaier Wolfgang , Mangold Elisabeth , Friedrichs Nicolaus , Propping Peter , Krüger Stefan , Gebert Johannes , Schmiegel Wolff , Rueschoff Josef , Loeffler Markus , Moeslein Gabriela
Published: August 2006

Purpose

Lynch syndrome is linked to germline mutations in mismatch repair genes. We analyzed the genotype-phenotype correlations in the largest cohort so far reported.

Patients and Methods

Following standard algorithms, we identified 281 of 574 unrelated families with deleterious germline mutations in MLH1 (n = 124) or MSH2 (n = 157). A total of 988 patients with 1,381 cancers were included in this analysis.

Results

We identified 181 and 259 individuals with proven or obligatory and 254 and 294 with assumed MLH1 and MSH2 mutations, respectively. Age at diagnosis was younger both in regard to first cancer (40 v 43 years; P < .009) and to first colorectal cancer (CRC; 41 v 44 years; P = .004) in MLH1 (n = 435) versus MSH2 (n = 553) mutation carriers. In both groups, rectal cancers were remarkably frequent, and the time span between first and second CRC was smaller if the first primary occurred left sided. Gastric cancer was the third most frequent malignancy occurring without a similarly affected relative in most cases. All prostate cancers occurred in MSH2 mutation carriers.

Conclusion

The proportion of rectal cancers and shorter time span to metachronous cancers indicates the need for a defined treatment strategy for primary rectal cancers in hereditary nonpolyposis colorectal cancer patients. Male MLH1 mutation carriers require earlier colonoscopy beginning at age 20 years. We propose regular gastric surveillance starting at age 35 years, regardless of the familial occurrence of this cancer. The association of prostate cancer with MSH2 mutations should be taken into consideration both for clinical and genetic counseling practice.
T-Cell Immunity to the Folate Receptor Alpha Is Prevalent in Women With Breast or Ovarian Cancer
Authors: Knutson Keith L. , Krco Christopher J. , Erskine Courtney L. , Goodman Karin , Kelemen Linda E. , Wettstein Peter J. , Low Philip S. , Hartmann Lynn C. , Kalli Kimberly R.
Published: August 2006

Purpose

Studies have demonstrated that the generation of immunity to tumor antigens is associated with improved prognosis for many cancers. A candidate antigen is the folate receptor alpha (FRα), which is overexpressed in breast and ovarian cancers. Our goal in this study was to attain a better understanding of the extent of endogenous FRα immunity.

Methods

Using a CD4+T cell epitope prediction algorithm, we predicted promiscuous epitopes of FRα, and tested for immunity in 30 breast (n = 17) or ovarian (n = 13) cancer patients and 18 healthy donors using enzyme-linked immunospot analysis.

Results

Fourteen peptides were predicted, seven each from the carboxy- and amino-terminus halves of the protein. More than 70% of patients demonstrated immunity to at least one FRα peptide. Patients responded to an average of 3 ± 0.5 peptides, whereas healthy donors responded to 1 ± 0.4 peptides (P = .004). Five peptides were recognized by more than 25% of patients. Responses to three peptides were higher (P < .05) in patients than in healthy donors, suggesting augmented immunity. Compared with healthy individuals, patients developed higher immunity to the amino-terminus half of the receptor (P = .03). There was no difference between each group in the responses to nonspecific (P = .2) and viral stimuli (P = .5). Lastly, patients demonstrated elevated levels of FRα antibodies consistent with a coordinated immune response.

Conclusion

These findings demonstrate that the FRα is a target of the immune system in breast and ovarian cancer patients. Understanding which antigens are targeted by the immune system may be important for prognosis or immune-based therapies.
Somatic Activation of KIT in Distinct Subtypes of Melanoma
Authors: Curtin John A. , Busam Klaus , Pinkel Daniel , Bastian Boris C.
Published: August 2006

Purpose

Melanomas on mucosal membranes, acral skin (soles, palms, and nail bed), and skin with chronic sun-induced damage have infrequent mutations in BRAF and NRAS, genes within the mitogen-activated protein (MAP) kinase pathway commonly mutated in melanomas on intermittently sun-exposed skin. This raises the question of whether other aberrations are occurring in the MAP kinase cascade in the melanoma types with infrequent mutations of BRAF and NRAS.

Patients and Methods

We analyzed array comparative genomic hybridization data from 102 primary melanomas (38 from mucosa, 28 from acral skin, and 18 from skin with and 18 from skin without chronic sun-induced damage) for DNA copy number aberrations specific to melanoma subtypes where mutations in BRAF and NRAS are infrequent. A narrow amplification on 4q12 was found, and candidate genes within it were analyzed.

Results

Oncogenic mutations in KIT were found in three of seven tumors with amplifications. Examination of all 102 primary melanomas found mutations and/or copy number increases of KIT in 39% of mucosal, 36% of acral, and 28% of melanomas on chronically sun-damaged skin, but not in any (0%) melanomas on skin without chronic sun damage. Seventy-nine percent of tumors with mutations and 53% of tumors with multiple copies of KIT demonstrated increased KIT protein levels.

Conclusion

KIT is an important oncogene in melanoma. Because the majority of the KIT mutations we found in melanoma also occur in imatinib-responsive cancers of other types, imatinib may offer an immediate therapeutic benefit for a significant proportion of the global melanoma burden.
RETRACTED: Focusing properties of a photonic crystal slab with multiple mechanisms in addition to negative refraction
Authors: Fang Yun-tuan , Zhou Jun
Published: August 2006

The abstract for this paper has been replaced with the following editorial
note: It has come to the attention of the Optical Society of America that this
article should not have been submitted owing to its substantial replication, without
appropriate attribution, of significant elements found in the following published
material: Y. Fang and Q. Zhou, "The imaging properties of photonic crystal slabs with
effective negative refraction indexes" Appl. Phy. B, Vol. 83, No. 4 (June 2006), pp.
587-594.
Early Manifestation of Type 1 Diabetes in Children Is a Risk Factor for Changed Bone Geometry: Data Using Peripheral Quantitative Computed Tomography
Authors: Bechtold Susanne , Dirlenbach Isa , Raile Klemens , Noelle Vera , Bonfig Walter , Schwarz Hans Peter
Published: August 2006

OBJECTIVE. Normal to severely decreased bone mineral density has been reported in children with type 1 diabetes. To detect possible abnormalities in bone mineralization, geometry, and muscle bone unit, we measured selective parameters in children with type 1 diabetes using peripheral quantitative computed tomography.

METHODS. Measurements of the radius by peripheral quantitative computed tomography were made to assess cortical and trabecular bone characteristics as well as muscle mass in 88 patients (42 girls, 46 boys) at a mean age of 11.7 ± 3.0 years, a mean disease duration of 5.6 ± 3.7 years, and a mean manifestation age of type 1 diabetes of 6.1 ± 3.5 years. Height, weight, Tanner stage, insulin regimen, and glycosylated hemoglobin values were recorded. Bone metabolism was studied by measurement of bone formation and bone resorption parameters. Dynamic muscle force was measured using a grip strength device.

RESULTS. Overall, cortical, trabecular, and total bone mineral density were within the reference range. Total and cortical bone cross-sectional area and muscle mass were low in prepubertal patients, and total cross-sectional area was low in early puberty. Adolescent patients showed normal bone and muscle parameters. Grip strength and recreational physical activity were normal in all in relation to a healthy reference population. In a subgroup of 18 patients, early manifestation of type 1 diabetes was detected as a risk factor for altered bone development with significantly reduced cortical bone mineral density and total, cortical, and muscle cross-sectional area (−0.9 ± 1.3 SD, −2.1 ± 1.3 SD, −1.6 ± 0.7 SD, and −1.0 ± 0.7 SD, respectively). Bone characteristics were not influenced by metabolic control, disease duration, or insulin regimen.

CONCLUSIONS. Manifestation of type 1 diabetes at an early age may impair bone development. Longitudinal data are needed to determine whether this impairment persists into adolescence and adulthood.
Ten Engineers Reading: Disjunctions between Preference and Practice in Civil Engineering Faculty Responses
Authors: Taylor Summer Smith , Patton Martha D.
Published: August 2006

Previous research has indicated that engineering faculty do not follow best practices when commenting on students' technical writing. However, it is unclear whether the faculty prefer to comment in these ineffective ways, or whether they prefer more effective practices but simply do not enact them. This study adapts a well known study of response in composition to ask whether engineering faculty prefer authoritative, form-focused comments, or whether they may prefer to write different sorts of comments. We asked ten civil engineering faculty to comment on a sample paper and then rank their preferences for provided versions of comments on the same paper. One provided version emphasized comments on content, one emphasized comments on form, and one was balanced. Comparisons of the respondents' preferences and practices suggest that the engineering faculty recognize and value content-focused, non-authoritative responses, but generally do not write comments that conform to these values. We consider the implication of these findings for research on response to technical writing as well as for technical writing faculty in their own course. While recognizing the need for more research, we also discuss ways in which writing professionals, including WAC administrators and technical writing professors, can encourage engineering faculty to enact their preferences for response styles that reflect best practices.
Efficacy of training in theriogenology as determined by a survey of veterinarians
Authors: Root Kustritz Margaret V. , Chenoweth Peter J. , Tibary Ahmed
Published: August 2006

Objective—To determine whether veterinarians perceive that theriogenology training at veterinary medical schools in North America and the Caribbean is adequate for achievement of theriogenology skills commonly used in private practice.

Procedures—A survey was mailed to members of the veterinary medical associations of Alabama, Kansas, Pennsylvania, and Washington. With regard to reproductive procedures in bovine, equine, porcine, small ruminant, camelid, and small animal species, veterinarians (predominantly practitioners) were asked to rate the importance of that procedure in their job and to assess their own degree of competency in that procedure at the time of their graduation from veterinary school.

Results—Procedures considered most valuable in practice were those that represent basic theriogenology education and training, such as transrectal palpation of cows and mares and interpretation of vaginal cytologic specimens in bitches. Dystocia management was a high priority in all species. Correlations between rankings for value in practice and competency at graduation were good, varying from 0.75 in cattle and 0.78 in horses to 0.98 in dogs and 1.0 in cats, small ruminants, and pigs.

Conclusions—Analysis of these data suggests that appropriate theriogenology procedures are being taught in veterinary medical schools but perhaps not to the extent required to achieve adequate competency immediately at graduation. Issues requiring further investigation include the effect of tracking in the veterinary curriculum on theriogenology training, methods by which more students could receive greater practical exposure during theriogenology training, and the apparent relative lack of theriogenology training (including contraception) in small animals and exotic animals.
Intramuscular administration of a low dose of ACTH for ACTH stimulation testing in dogs
Authors: Behrend Ellen N. , Kemppainen Robert J. , Bruyette David S. , Busch Katherine A. , Lee Hollie P.
Published: August 2006

Objective—To compare adrenal gland stimulation achieved following administration of cosyntropin (5 μg/kg [2.3 μg/lb]) IM versus IV in healthy dogs and dogs with hyperadrenocorticism.

Design—Clinical trial.

Animals—9 healthy dogs and 9 dogs with hyperadrenocorticism.

Procedures—In both groups, ACTH stimulation was performed twice. Healthy dogs were randomly assigned to receive cosyntropin IM or IV first, but all dogs with hyperadrenocorticism received cosyntropin IV first. In healthy dogs, serum cortisol concentration was measured before (baseline) and 30, 60, 90, and 120 minutes after cosyntropin administration. In dogs with hyperadrenocorticism, serum cortisol concentration was measured before and 60 minutes after cosyntropin administration.

Results—In the healthy dogs, serum cortisol concentration increased significantly after administration of cosyntropin, regardless of route of administration, and serum cortisol concentrations after IM administration were not significantly different from concentrations after IV administration. For both routes of administration, serum cortisol concentration peaked 60 or 90 minutes after cosyntropin administration. In dogs with hyperadrenocorticism, serum cortisol concentration was significantly increased 60 minutes after cosyntropin administration, compared with baseline concentration, and concentrations after IM administration were not significantly different from concentrations after IV administration.

Conclusions and Clinical Relevance—Results suggest that in healthy dogs and dogs with hyperadrenocorticism, administration of cosyntropin at a dose of 5 μg/kg, IV or IM, resulted in equivalent adrenal gland stimulation.
Evaluation of ilial screw loosening after triple pelvic osteotomy in dogs: 227 cases (1991–1999)
Authors: Doornink Michael T. , Nieves Mary A. , Evans Richard
Published: August 2006

Objective—To investigate factors influencing screw loosening after triple pelvic osteotomy (TPO) and ischial wire stabilization of the acetabular segment.

Design—Retrospective case series.

Animals—227 dogs with congenital hip dysplasia or subluxated hip joints.

Procedures—Medical records and radiographs of 227 dogs that underwent 332 TPO procedures were evaluated, and data pertaining to screw type, plate position, sacral screw engagement, use of ischial interfragmentary wires, and pelvic alignment were assessed for associations with screw loosening.

Results—Complications developed in 96 of the 332 (29%) procedures. Cancellous screws without sacral engagement were associated with the lowest frequency (6%) of loosening, compared with cancellous and cortical screws engaging the sacrum and cortical screws that did not engage the sacrum. Frequency of screw loosening increased when cortical or cancellous screws engaged the sacrum and when cortical screws were used. In dogs that had surgery bilaterally, the first limb on which TPO was performed had a higher frequency of screw loosening than the second limb. Pelvic alignment loss was greatest (5.4°) when the 3 most cranial screws were loosened. Loss of pelvic alignment was significantly different between dogs that underwent surgery and had complications and those that underwent surgery and did not have complications in association with loosening of 1, 2, and 3 screws.

Conclusions and Clinical Relevance—TPO screw loosening was multifactorial and related to stability of the affected ilium, screw type, and screw position. Placing cancellous screws that do not engage the sacrum in pelvic osteotomy plate positions 1 through 3 may decrease the number of screws that loosen.
Efficacy of tulathromycin for treatment of cattle with acute ocular Moraxella bovis infections
Authors: Lane V. Michael , George Lisle W. , Cleaver Dawn M.
Published: August 2006

Objective—To evaluate the clinical efficacy of a single injection of tulathromycin, compared with saline (0.9% NaCl) solution-treated control calves, for treatment of induced infectious bovine keratoconjunctivitis in calves.

Design—Clinical trial.

Animals—30 Holstein bull calves ranging from 5 to 6 months old and 75 to 200 kg (165 to 440 lb) with no history of Moraxella bovis infections, no history of M bovis vaccination, and negative results for M bovis on 3 consecutive ocular bacterial cultures.

Procedures—Both eyes of each calf were infected with 1 X 1010 colony-forming units of piliated M bovis for 3 consecutive days prior to the trial. On day 0, ocular lesion scores were determined for each calf and the calves were weighed and assigned to a treatment (2.5 mg/kg [1.14 mg/lb] of body weight, SC) or control group according to a stratified random allocation based on weight and lesion score. Eyes were stained with fluorescein and photographed daily to record healing. Eyes were evaluated bacteriologically for M bovis on days 0 to 6 and at 3-day intervals thereafter.

Results—Median time to ulcer resolution in calves treated with tulathromycin was 9.1 days. More than 50% of control calves still had ulcers at the end of the trial (21 days). Moraxella sp was isolated less often from the eyes of treated calves than from the control calves. By day 10, the treated calves had lower ocular lesion scores than control calves.

Conclusions and Clinical Relevance—A single dose of tulathromycin (SC) was an effective treatment of calves with experimentally induced infectious bovine keratoconjunctivitis. The long serum half-life of tulathromycin, along with the results of this trial, suggests that tulathromycin may be a rational choice as a single-injection treatment for infectious bovine keratoconjunctivitis.
Cover Picture: 3D Polymer Microframes That Exploit Length‐Scale‐Dependent Mechanical Behavior (Adv. Mater. 16/2006)
Authors: Jang J.‐H. , Ullal C. K. , Choi T. , Lemieux M. C. , Tsukruk V. V. , Thomas E. L.
Published: August 2006

The cover shows a simulation of a four‐functional microframe network undergoing plastic deformation, illustrating the significant ductility of the connector struts between nodes, as reported for such microframes fabricated by Thomas and co‐workers on p. 2123. The inset shows a scanning electron microscopy image of an SU8 epoxy microframe in a region of the structure with large strain‐to‐break of the component struts.
Inside Front Cover: A Supramolecular Approach to Optically Anisotropic Materials: Photosensitive Ionic Self‐Assembly Complexes (Adv. Mater. 16/2006)
Authors: Zakrevskyy Y. , Stumpe J. , Faul C. F. J.
Published: August 2006

Application of the supramolecular synthesis strategy ionic self‐assembly for the facile production of low‐molecular‐weight photosensitive materials is presented on p. 2133 by Stumpe, Faul, and Zakrevskyy. The materials so synthesized possess good film‐forming properties, are capable of undergoing light‐induced generation of optical anisotropy, and possess dichroic ratios of approximately 50.
Activation of mammalian target of rapamycin in cytomegalic neurons of human cortical dysplasia
Authors: Ljungberg M. Cecilia , Bhattacharjee Meenakshi B. , Lu Yaojuan , Armstrong Dawna L. , Yoshor Daniel , Swann John W. , Sheldon Michael , D'Arcangelo Gabriella
Published: August 2006

Objective

The cortex of patients with cortical dysplasia contains several abnormal cell types. Among the dysplastic cells, cytomegalic neurons are known to be electrically hyperactive and may contribute to epileptic activity. In this study, we sought to identify molecular markers of cytomegalic neurons in focal or hemispheric cortical dysplasia and to determine whether the activity of the mammalian target of rapamycin (mTOR) kinase is abnormally high in these cells.

Methods

Microarray analysis of gene expression in large dysplastic cells microdissected from cortical dysplasia surgical specimens was used to identify markers of cytomegalic neurons. Immunohistochemistry and immunofluorescence analysis of cortical sections was used to validate the microarray results and to probe the activity of mTOR in cytomegalic neurons using phospho‐specific antibodies directed against known mTOR targets.

Results

We demonstrate that the neurofilament heavy chain is a reliable marker of cytomegalic neurons and that targets of the mTOR kinase, such as the ribosomal protein S6, eIF4G, and Akt, are hyperphosphorylated in these dysplastic neurons.

Interpretation

We conclude that mTOR kinase hyperactivation is a molecular mechanism underlying the development of cytomegalic neurons. This finding may lead to the development of novel therapeutic approaches for childhood epilepsy associated with cortical dysplasia. Ann Neurol 2006
“Durch den Raum” konjugierte Cyclophanpolymere
Authors: Morisaki Yasuhiro , Chujo Yoshiki
Published: August 2006

Konjugierte Polymere haben einzigartige optische und elektronische Eigenschaften, die zu vielfältigen Anwendungen als optoelektronische Materialien und molekulare Funktionseinheiten geführt haben. Während aber in der Chemie sowohl der Cyclophane als auch der konjugierten Polymere bemerkenswerte Fortschritte zu verzeichnen sind, wurden bislang nur wenige Beispiele für Synthesen von konjugierten Polymeren mit Cyclophaneinheiten in der Hauptkette beschrieben. Dieser Kurzaufsatz fasst aktuelle Entwicklungen bezüglich Synthesen, Eigenschaften und Anwendungen von “durch den Raum” konjugierten Polymeren auf Cyclophanbasis zusammen.
The use of volunteers for conducting sponge biodiversity assessments and monitoring using a morphological approach on Indo‐Pacific coral reefs
Authors: Bell James J.
Published: August 2006

Sponges are an important component of coral reef ecosystems, but even though they are widespread with the ability to significantly influence other benthic community members they rarely feature to any great extent in current monitoring or biodiversity assessment programmes conducted by volunteer and professional groups. This exclusion is usually because of the taxonomic problems associated with sponge identification.

A potential alternative to monitoring temporal or spatial change in sponge assemblages and assessing biodiversity levels is to characterize sponges using morphologies present rather than collecting species data. Quantifying sponge biodiversity (for monitoring and biodiversity assessments) at the morphological level is less time and resource consuming than collecting species data and more suited to groups with little training and experience of sponge taxonomy or in regions where detailed taxonomic information on sponges is sparse.

This paper considers whether the same differences and similarities in sponge richness and assemblage composition can be identified using species and morphological data in response to environmental gradients at two coral reef ecosystems in south‐east Sulawesi, Indonesia, and whether volunteers can be used to reliably collect morphological information. Sponge morphologies were classified into 14 groups and different morphological assemblages were found by the author at the two sites and between depth intervals. Comparisons of sponge species and morphological composition data showed that common patterns in assemblage structuring and richness could be identified irrespective of whether morphological or species data were used. In addition, a positive linear relationship was found between sponge species and morphological richness.

The morphological data recorded by volunteer divers (n=10) were compared with that collected by the author. Although volunteers recorded fewer sponges than the author (approximately 15% less), missing mainly small encrusting specimens, similar assemblage structure could be identified from both the volunteers' and the author's data.

The results showed that the same differences in sponge assemblages between sites and depths could be identified from both species and morphological data. In addition, these morphological data could be reliably collected by volunteer divers.

Copyright © 2006 John Wiley & Sons, Ltd.
Microwave‐Assisted Heterogeneous Cross‐Coupling Reactions Catalyzed by Nickel‐in‐Charcoal (Ni/C)
Authors: Lipshutz Bruce H. , Frieman Bryan A. , Lee Ching‐Tien , Lower Asher , Nihan Danielle M. , Taft Benjamin R.
Published: August 2006

A study involving the relatively rare combination of heterogeneous catalysis conducted under microwave conditions is presented. Carbon–carbon bond formation, including Negishi and Suzuki couplings, can be quickly effected with aryl chloride partners by using a base metal (nickel) adsorbed in the pores of activated charcoal. Aminations were also studied, along with cross‐couplings of vinyl alanes with benzylic chlorides as a means to stereodefined allylated aromatics. Reaction times for all these processes are typically reduced from several hours to minutes in a microwave reactor.
Determination of the Cryptic Stereochemistry of the First PKS Chain‐Extension Step in Ansamitocin Biosynthesis by Actinosynnema pretiosum
Authors: Kubota Takaaki , Brünjes Marco , Frenzel Thomas , Xu Jun , Kirschning Andreas , Floss Heinz G.
Published: August 2006

The biosynthesis of the antitumor antibiotic, ansamitocin, involves the assembly of a linear octaketide on the ansamitocin (asm) polyketide synthase (PKS), which is then cyclized to proansamitocin and further modified to the final product. In the first chain‐extension step on the asm PKS, a stereocenter is generated which is then obliterated in a subsequent double‐bond migration. The cryptic configuration at this stereocenter was determined by first synthesizing the two enantiomers of the intermediate diketide as their N‐acetylcysteamine (SNAC) thioesters. These were then used to demonstrate that only the R enantiomer complements a 3‐amino‐5‐hydroxybenzoic acid (AHBA) deficient mutant of Actinosynnema pretiosum to restore ansamitocin formation. The low efficiency of complementation by the diketide, compared to AHBA, is due to inefficient loading onto the PKS and not the inhibition of the enzyme. A presumed next chain‐extension intermediate—the triketide with an unrearranged double bond—was also synthesized as its SNAC ester, but did not complement the AHBA− mutant.