bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial defence mechanisms of the human parotid duct
Authors: Kutta H. , May J. , Jaehne M. , Münscher A. , Paulsen F. P. 
Published: April 2006

AbstractThe parotid duct transports saliva from the gland into the oral cavity. However, its immune response properties, along with the secretion and moistening principles of the duct, have not yet been fully investigated. These properties may play an important role in protecting the parotid gland from infection and also prevent development of sialodocholithiasis, as the parotid duct – in contrast to the submandibular salivary duct – is often free of duct concrements. Up to now, only the parotid gland has been investigated, without regard to its duct. The present study analyses the structures of the parotid duct in their relations to antimicrobial defence mechanisms and rheological properties. Investigations were performed on 23 parotid ducts using histological, histochemical and immunohistochemical methods. Epithelial and goblet cells of the parotid duct synthesize a complex mucous layer that covers the epithelium. The viscosity is influenced by secreted mucins and TFF peptides. This layer contains carbohydrates including N‐acetyl‐glucosamine, N‐acetyl‐galactosamine, galactose, mannose, fucose and sialic acids. The lamina propria contains granulocytes, T lymphocytes and macrophages. IgA, produced by plasma cells in the subepithelial layer, is frequently integrated in the secretory product. Synthesized mucins, TFF peptides, carbohydrates and immunoglobulins form a complex layer that can be expected to prohibit infection and enables salivary flow. Our study demonstrates that the steady secretion of the parotid gland, together with the ductal cellular and biochemical immune protection system, is likely to thwart ascending infections in the parotid duct and gland.
Vitamin E protected cultured cortical neurons from oxidative stress‐induced cell death through the activation of mitogen‐activated protein kinase and phosphatidylinositol 3‐kinase
Authors: Numakawa Yumiko , Numakawa Tadahiro , Matsumoto Tomoya , Yagasaki Yuki , Kumamaru Emi , Kunugi Hiroshi , Taguchi Takahisa , Niki Etsuo 
Published: April 2006

AbstractThe role of vitamin E in the CNS has not been fully elucidated. In the present study, we found that pre‐treatment with vitamin E analogs including αT (α‐tocopherol), αT3 (α ‐tocotrienol), γT, and γT3 for 24 h prevented the cultured cortical neurons from cell death in oxidative stress stimulated by H2O2, while Trolox, a cell‐permeable analog of αT, did not. The preventive effect of αT was dependent on de novo protein synthesis. Furthermore, we found that αT exposure induced the activation of both the MAP kinase (MAPK) and PI3 kinase (PI3K) pathways and that the αT‐dependent survival effect was blocked by the inhibitors, U0126 (an MAPK pathway inhibitor) or LY294002 (a PI3K pathway inhibitor). Interestingly, the up‐regulation of Bcl‐2 (survival promoting molecule) was induced by αT application. The up‐regulation of Bcl‐2 did not occur in the presence of U0126 or LY294002, suggesting that αT‐up‐regulated Bcl‐2 is mediated by these kinase pathways. These observations suggest that vitamin E analogs play an essential role in neuronal maintenance and survival in the CNS.
Test–retest reliability for two indices of ventilatory efficiency measured during cardiopulmonary exercise testing in healthy men and women
Authors: Davis James A. , Sorrentino Kristin M. , Ninness Erin M. , Pham Patrick H. , Dorado Silvia , Costello Kara B. 
Published: April 2006

SummaryThe level of ventilation (E) at a given carbon dioxide output (CO2) determines ventilatory efficiency. During cardiopulmonary exercise testing (CPET), ventilatory efficiency can be measured as the slope of the E versus CO2 relationship or the lowest /CO2. We evaluated the test–retest reliability of these two ventilatory efficiency indices in 29 healthy subjects (14 males). Each subject performed duplicate cycle ergometer tests on different days. Ventilation and the gas fractions for oxygen and CO2 were measured with a Vacumed metabolic cart. Linear regression analysis of the versus CO2 slope for the duplicate tests in the males, females, and both sexes combined yielded correlation coefficients of 0·822, 0·942, and 0·910, respectively. The corresponding correlation coefficients for the lowest /CO2 were 0·745, 0·929, and 0·884. A comparison of the test–retest correlation coefficients between the two ventilatory efficiency measures for the men, women, and both sexes combined revealed that they were not significantly different and, for a given index, there were no sex differences. The bias (mean of difference scores between tests) and 95% limits of agreement for the versus CO2 slope in the males, females, and both sexes combined were −0·05 ± 2·41, −0·57 ± 1·92, and −0·32 ± 2·20, respectively. The bias and 95% limits of agreement for the lowest /CO2 were very similar with values of 0·06 ± 2·45, −0·22 ± 2·03, and −0·10 ± 2·27. We conclude that the test–retest reliability for the versus CO2 slope and the lowest /CO2 is the same and that there is no sex difference in reliability for either index of ventilatory efficiency.
Use of a Pine Bark Extract and Antioxidant Vitamin Combination Product as Therapy for Migraine in Patients Refractory to Pharmacologic Medication
Authors: Chayasirisobhon Sirichai 
Published: April 2006

Objective.—To evaluate the potential benefit of a pine bark extract and antioxidant vitamin combination product in the treatment of migraine headache.Background.—This was an uncontrolled preliminary study to investigate the potential of an antioxidant formulation as therapy for migraine headache.Methods.—Twelve patients with a long‐term history of migraine with and without aura who had failed to respond to multiple treatments with β‐blockers, antidepressants, anticonvulsants, and 5‐hydroxytryptamine receptor agonists were selected for the study. They were treated with 10 capsules of an antioxidant formulation of 120 mg pine bark extract, 60 mg vitamin C, and 30 IU vitamin E in each capsule daily for 3 months. Following enrollment patients completed a migraine disability assessment (MIDAS) questionnaire to give a baseline measure of migraine impact on work, school, domestic, and social activities over the previous 3 months. Patients were then treated for 3 months with the antioxidant formulation while continuing to receive existing pharmacologic medications. A second MIDAS was given at the conclusion of the treatment period.Results.—There was a significant mean improvement in MIDAS score of 50.6% for the 3‐month treatment period compared with the 3 months prior to baseline (P < .005). The treatment was also associated with significant reductions in number of headache days and headache severity score. Mean number of headache days was reduced from 44.4 days at baseline (95% CI 28.9 to 59.8) to 26.0 days (95% CI 5.3 to 46.7; P < .005) after 3 months' therapy and mean headache severity was reduced from 7.5 of 10 (95% CI 6.7 to 8.4) to 5.5 (95% CI 4.1 to 7.0; P < .005).Conclusion.—These data suggest that the antioxidant therapy used in this study may be beneficial in the treatment of migraine possibly reducing headache frequency and severity. Further clinical investigation into the efficacy of antioxidant as therapy for chronic migraine is warranted.
POPULATION SIZE, DISTRIBUTION, AND BEHAVIOR OF INDO‐PACIFIC BOTTLENOSE (TURSIOPS ADUNCUS) AND HUMPBACK (SOUSA CHINENSIS) DOLPHINS OFF THE SOUTH COAST OF ZANZIBAR
Authors: Stensland Eva , Carlén Ida , Särnblad Anna , Bignert Anders , Berggren Per 
Published: April 2006

AbstractIndo‐Pacific bottlenose (Tursiops aduncus) and humpback dolphins (Sousa chinensis) off the south coast of Zanzibar, East Africa, have been subject to both direct and indirect takes as well as disturbance from local dolphin tourism during the last decade. Meanwhile, little or no information on population parameters exists for these animals. In order to assess the anthropogenic threats, a study was conducted between 1999 and 2002 to determine population sizes, distribution, and behavior of these animals. Population sizes were calculated for each year using mark‐recapture methods applied to photo‐identification data. The estimates ranged between 136 and 179 for the bottlenose dolphins and between 58 and 65 for the humpback dolphins in the calculated 26 km2 study area. Patterns in distribution and behavior were investigated using image and spatial statistic software on data from boat surveys. Analyses of spatial densities showed that both species concentrated their activities to smaller areas (2%–11.5%) within the study area. When the study results were considered in light of the anthropogenic threats, it was clear that immediate conservation measures were needed. This is critical if the negative impact on the species is to be minimized and the dolphins are to continue to represent a socioeconomic resource in the region.
Potent Antitumor Activity of an Auristatin-Conjugated, Fully Human Monoclonal Antibody to Prostate-Specific Membrane Antigen
Authors: Ma Dangshe , Hopf Christine E. , Malewicz Andrew D. , Donovan Gerald P. , Senter Peter D. , Goeckeler William F. , Maddon Paul J. , Olson William C. 
Published: April 2006

Abstract
Prostate-specific membrane antigen (PSMA) is the prototypic cell-surface marker of prostate cancer and provides an attractive target for monoclonal antibody (mAb) targeted therapies. In this study, a novel antibody-drug conjugate (ADC) was generated by linking a fully human PSMA mAb to monomethylauristatin E (MMAE), a potent inhibitor of tubulin polymerization. The PSMA ADC was evaluated for antitumor activity in vitro and in a mouse xenograft model of androgen-independent human prostate cancer. The PSMA ADC eliminated PSMA-expressing cells with picomolar potency and &gt;700-fold selectivity in culture. When used to treat mice with established human C4-2 tumors, the PSMA ADC significantly improved median survival 9-fold relative to vehicle or isotype-matched ADC (P = 0.0018) without toxicity. Treatment effects were also manifest as significant (P = 0.0068) reduction in serum levels of prostate-specific antigen (PSA). Importantly, 40% of treated animals had no detectable tumor or measurable PSA at day 500 and could be considered cured. The findings support development of PSMA antibody-auristatin conjugates for therapy of prostate cancer.
Rapamycin Inhibits Growth of Premalignant and Malignant Mammary Lesions in a Mouse Model of Ductal Carcinoma In situ
Authors: Namba Ruria , Young Lawrence J.T. , Abbey Craig K. , Kim Lisa , Damonte Patrizia , Borowsky Alexander D. , Qi Jinyi , Tepper Clifford G. , MacLeod Carol L. , Cardiff Robert D. , Gregg Jeffrey P. 
Published: April 2006

Abstract
Purpose: Rapamycin has been shown to have antitumor effects in various tumor models. To study the effect of rapamycin at different stages of breast cancer development, we used two unique mouse models of breast cancer with activated phosphatidylinositol 3-kinase (PI3K) pathway. Met-1 tumors are highly invasive and metastatic, and mammary intraepithelial neoplasia-outgrowths (MIN-O), a model for human ductal carcinoma in situ, are transplantable premalignant mammary lesions that develop invasive carcinoma with predictable latencies. Both of these models were derived from mammary lesions in Tg(MMTV-PyV-mT) mice.
Experimental Design: Met-1 tumors were used to study the effect of rapamycin treatment on invasive disease. Transplanted MIN-O model was used to study the effect of rapamycin on premalignant mammary lesions. Animals were in vivo micro–positron emission tomography imaged to follow the lesion growth and transformation to tumor during the treatment. Cell proliferation, angiogenesis, and apoptosis was assayed by immunohistochemistry.
Results: Rapamycin inhibited in vitro tumor cell proliferation and in vivo Met-1 tumor growth. The growth inhibition was correlated with dephosphorylation of mammalian target of rapamycin (mTOR) targets. Rapamycin treatment significantly reduced the growth of the premalignant MIN-O lesion, as well as tumor incidence and tumor burden. Growth inhibition was associated with reduced cell proliferation and angiogenesis and increased apoptosis.
Conclusions: In PyV-mT mouse mammary models, rapamycin inhibits the growth of premalignant lesions and invasive tumors. Although the inhibitory effect of rapamycin was striking, rapamycin treatment did not completely obliterate the lesions.
Reduced Plasma RNA Integrity in Nasopharyngeal Carcinoma Patients
Authors: Wong Blenda C.K. , Chan K.C. Allen , Chan Anthony T.C. , Leung Sing-Fai , Chan Lisa Y.S. , Chow Katherine C.K. , Lo Y.M. Dennis 
Published: April 2006

Abstract
Purpose: Recent research has shown the feasibility of detecting cell-free RNA markers in human subjects. As elevated RNase activity has previously been described in the circulation of cancer patients, we hypothesized that cancer patients may have reduced plasma RNA integrity. In this study, we used nasopharyngeal carcinoma (NPC) as a model system to test this hypothesis.
Experimental Design: Plasma RNA integrity was determined using the ratio of the concentrations of transcript sequences corresponding to the 3′ to those from the 5′ end of a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Transcript concentrations were measured using real-time quantitative reverse transcription-PCR assays targeting the 5′ and 3′ regions. We analyzed the plasma RNA integrity in 49 untreated NPC patients and 53 healthy controls. We also assessed the plasma samples from 19 NPC patients before and after radiotherapy to further show the clinical potential of this marker.
Results: The 3′ to 5′ GAPDH ratio was significantly lower in the plasma of untreated NPC patients when compared with healthy controls (0.0252 versus 0.0485, P = 0.024). Statistical analysis showed that plasma GAPDH ratio was correlated with tumor stage but not with sex and age. Moreover, 14 of 19 NPC patients (74%) showed significant increase in the plasma GAPDH ratio following radiotherapy (P = 0.003). All of these patients were in clinical remission after treatment.
Conclusions: Our findings suggest that NPC is associated with disturbances in the integrity of cell-free circulating RNA, raising the possibility that measurement of plasma RNA integrity may serve as a useful marker for the diagnosis and monitoring of malignant diseases.
Molecular Evidence for the Same Clonal Origin of Multifocal Papillary Thyroid Carcinomas
Authors: McCarthy Ryan P. , Wang Mingsheng , Jones Timothy D. , Strate Randall W. , Cheng Liang 
Published: April 2006

Abstract
Purpose: Patients with papillary thyroid carcinoma often have two or more distinct papillary tumors at thyroidectomy. Whether these multifocal papillary lesions are clonally related or whether they arise independently is unknown as previous studies have shown conflicting results. Molecular analysis of microsatellite alterations and X-chromosome inactivation status in separate tumors from the same patient can be used to define the genetic relationships among the multiple coexisting tumors.
Experimental Design: We examined 64 separate tumors from 22 female patients who underwent thyroidectomy for thyroid carcinoma. All patients had multiple and separate papillary carcinomas (range, two to six). Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. Loss of heterozygosity assays for three microsatellite polymorphic markers for putative tumor suppressor genes on chromosomes 3p25 (D3S1597), 9p21 (D9S161), and 18p11.22-p11 (D18S53) were done. In addition, X-chromosome inactivation analysis was done on the tumors from all patients.
Results: Twenty of 22 (91%) cases showed allelic loss in one or more of the papillary lesions in at least one of the three polymorphic markers analyzed. Concordant allelic loss patterns between coexisting papillary tumors were seen in 20 of 23 (87%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the multiple coexisting papillary lesions was seen in all informative cases.
Conclusion: Our data suggest that the multifocal tumors in patients with papillary thyroid carcinoma often arise from the same clone. Thus, intrathryoid metastasis may play an important role in the spread of papillary thyroid carcinoma, a finding that has important therapeutic, diagnostic, and prognostic implications.
Medial Opening Wedge Tibial Osteotomy and the Sagittal Plane
Authors: Rodner Craig M. , Adams Douglas J. , Diaz-Doran Vilmaris , Tate Janet P. , Santangelo Stephen A. , Mazzocca Augustus D. , Arciero Robert A. 
Published: April 2006

Background Altering the tibial slope in an anterior cruciate ligament–deficient knee has been shown to affect anterior-posterior tibial translation. The effects on articular contact pressure of altering tibial slope during a high tibial osteotomy are unknown. Hypotheses Performing an opening wedge osteotomy anterior to the midaxial line will increase tibial slope. Increasing tibial slope with a high tibial osteotomy in an anterior cruciate ligament–deficient knee redistributes tibiofemoral joint contact pressures onto the posterior tibial plateau. Study Design Controlled laboratory study. Methods Medial opening wedge high tibial osteotomies were performed, and a plate fixation with a known diameter inset was placed along the medial tibia in an anterior position and a posterior position on 9 cadaveric knees. Medial and lateral tibiofemoral contact pressures were measured at the resulting 2 different tibial slopes in both ligament-intact and ligament-deficient states using thin electronic sensors. Results Anterior plate application resulted in an increase in posterior tibial slope by an average of 6.6°(P <.001) compared with posterior plate placement. After medial opening wedge high tibial osteotomy, the mean peak lateral tibiofemoral contact pressure (3.4 MPa) was significantly greater (P=.002) than was the mean peak medial pressure (2.6 MPa). In ligament-intact specimens, altering the tibial slope did not significantly shift peak contact pressures. However, in ligament-deficient knees, increasing tibial slope by an average of 5.5° significantly redistributed the location of peak intra-articular pressure, shifting it posteriorly by 24% (P=.003). Conclusion Increasing tibial slope in anterior cruciate ligament–deficient knees with a high tibial osteotomy redistributes pressure into the posterior tibial plateau. Clinical Relevance In knees with chronic anterior cruciate ligament deficiency, posteromedial compartment degeneration is observed. Inadvertent redistribution of contact pressure into this area may be a cause of pain and premature clinical failure after medial opening wedge tibial osteotomy.
The experience of burden in India
Authors: Emmatty Leena Mary , Bhatti Ranbir S. , Mukalel Mathew T. 
Published: April 2006

Thirty caregivers of people living with dementia were investigated to examine the caregivers' experience of burden. The Clinical Dementia Rating Scale (CDRS), Burden Interviews and open-ended questions were administered on patients attending inpatient and outpatient services at the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore (India). Findings indicate that only 30 percent of the cases fell into the high burden group. No statistically significant results were observed between caregiver relationship and burden scores. Burden experienced in extended families was less compared to the other types of families. To conclude, the need to create awareness about the illness among different sections of the general population and interventions suited to the Indian caregivers are discussed.
Motion as a phenotype: the use of live-cell imaging and machine visual screening to characterize transcription-dependent chromosome dynamics
Authors: Drubin David A , Garakani Arman M , Silver Pamela A 
Published: April 2006

Abstract

Background
Gene transcriptional activity is well correlated with intra-nuclear position, especially relative to the nuclear periphery, which is a region classically associated with gene silencing. Recently however, actively transcribed genes have also been found localized to the nuclear periphery in the yeast Saccharomyces cerevisiae. When genes are activated, they become associated with the nuclear pore complex (NPC) at the nuclear envelope. Furthermore, chromosomes are not static structures, but exhibit constrained diffusion in real-time, live-cell studies of particular loci. The relationship of chromosome motion with transcriptional activation and active-gene recruitment to the nuclear periphery has not yet been investigated.

Results
We have generated a yeast strain that enables us to observe the motion of the galactose-inducible GAL gene locus relative to the nuclear periphery in real-time under transcriptionally active and repressed conditions. Using segmented geometric particle tracking, we show that the repressed GAL locus undergoes constrained diffusive movement, and that transcriptional induction with galactose is associated with an enrichment in cells with GAL loci that are both associated with the nuclear periphery and much more constrained in their movement. Furthermore, we report that the mRNA export factor Sac3 is involved in this galactose-induced enrichment of GAL loci at the nuclear periphery. In parallel, using a novel machine visual screening technique, we find that the motion of constrained GAL loci correlates with the motion of the cognate nuclei in galactose-induced cells.

Conclusion
Transcriptional activation of the GAL genes is associated with their tethering and motion constraint at the nuclear periphery. We describe a model of gene recruitment to the nuclear periphery involving gene diffusion and the mRNA export factor Sac3 that can be used as a framework for further experimentation. In addition, we applied to the analysis of chromosome motion a machine visual screening approach that used unbiased visual data rather than segmented geometric data. This novel analytical approach will allow for high-throughput study of processes that can be monitored via alterations in chromosome motion and connectivity with the nuclear periphery.