Avaliação quantitativa dos efeitos da levodopa e da estimulação do núcleo subtalâmico sobre o equilíbrio em pacientes com doença de Parkinson

INTRODUÇÃO: Os efeitos da levodopa (LD) e da estimulação cerebral profunda (ECP) de núcleo subtalâmico (STN) sobre o equilíbrio e sintomas axiais são até o momento controversos. OBJETIVOS: Avaliar quantitativamente os efeitos da ECP de STN e da LD sobre o equilíbrio estático em pacientes com DP operados, em comparação com a LD em pacientes não operados. MÉTODOS: Trinta e um pacientes submetidos a ECP de STN entre 3 meses e 1 ano e meio antes da avaliação e 26 controles portadores de DP não operados, estágios Hoehn e Yahr 2 a 4 foram avaliados usando UPDRS para avaliação clínica e plataforma de força para avaliar oscilações posturais. O primeiro grupo foi avaliado com ECP e sem medicação, com ECP e com medicação e sem ECP e sem medicação. O segundo grupo foi avaliado com e sem medicação. Cada paciente foi avaliado com os olhos abertos e fechados. O deslocamento do centro de pressão anteroposterior, laterolateral, a área, velocidade e deslocamento total linear foram medidos pela plataforma de força. Os dados paramétricos foram comparados usando o teste t de Student e os dados não-paramétricos foram comparados pelo teste de Kruskal-Wallis. A avaliação clínica consistiu na parte 3 da escala UPDRS e na escala Hoehn e Yahr. Nível de significância estatística considerada foi p=0,05. RESULTADOS: Os pacientes não operados oscilaram mais quando sob efeito da levodopa do que sem medicação. No grupo operado, a maior oscilação é no grupo com ECP desligada e sem medicação. Tende a reduzir sob efeito da ECP apresenta redução significativa sob efeito simultâneo de ECP e levodopa. CONCLUSÃO: A associação da ECP de NST com medicação tem impacto positivo sobre o controle postural. O efeito da ECP de NST reverte o efeito negativo da levodopa sobre as oscilações observadas em pacientes não operados

Geochemical data for drilled powder samples from two fossil Porites corals from Integrated Ocean Drilling Program Expedition 310

Fossil corals are unique archives of past seasonal climate variability, providing vital information about seasonal climate phenomena such as ENSO and monsoons. However, submarine diagenetic processes can potentially obscure the original climate signals and lead to false interpretations. Here we demonstrate the potential of laser ablation ICP-MS to rapidly detect secondary aragonite precipitates in fossil Porites colonies recovered by Integrated Ocean Drilling Program (IODP) Expedition 310 from submerged deglacial reefs off Tahiti. High resolution (100 µm) measurements of coralline B/Ca, Mg/Ca, S/Ca, and U/Ca ratios are used to distinguish areas of pristine skeleton from those afflicted with secondary aragonite. Measurements of coralline Sr/Ca, U/Ca and oxygen isotope ratios, from areas identified as pristine, reveal that the seasonal range of sea surface temperature in the tropical south Pacific during the last deglaciation (14.7 and 11 ka) was similar to that of today.

Chemical and isotopic compositions of pore fluids from ODP Sites 169-1034 and 169-1037

We have analysed the concentrations of Li, K, Rb, Cs, and B, and the isotopic ratios of Li and B of a suite of pore fluids recovered from ODP Sites 1037 (Leg 169; Escanaba Trough) and 1034 (Leg 169S; Saanich Inlet). In addition, we have analysed dissolved K, Rb, and Cs concentrations for estuarine mixing of the Ganges-Brahmaputra river system. Together, these data sets have been used to assess the role of sediments in the marine geochemical cycles of the alkali elements and boron. Uptake onto clay minerals during estuarine mixing removes 20-30% of the riverine input of dissolved Cs and Rb to the oceans. Prior to this study, the only other recognised sink of Rb and Cs was uptake during low-temperature alteration of the oceanic crust. Even with this additional sink there is an excess of inputs over outputs in their modern oceanic mass balance. Pore fluid data show that Li and Rb are transferred into marine sediments during early diagenesis. However, modeling of the Li isotope systematics of the pore fluids from Site 1037 shows that seawater Li taken up during marine sedimentation can be readily returned to solution in the presence of less hydrated cations, such as NH4+. This process also appears to result in high concentrations of pore fluid Cs (relative to local seawater) due to expulsion of adsorbed Cs from cation exchange sites. Flux calculations based on pore fluid data for a series of ODP sites indicate that early diagenesis of clay sediments removes around 8% of the modern riverine input of dissolved Li. Although NH4+-rich fluids do result in a flux of Cs to the oceans, on the global scale this input only augments the modern riverine Cs flux by ~3%. Nevertheless, this may have implications for the fate of radioactive Cs in the natural environment and waste repositories.

University of Michigan Field Hockey Team, 1994

Back Row: Amy Helber, Jamie Robbins, Brie Derr, Julie Flachs, Asleya Koreishi, Meredith Weinstein, Sandra Cabrera, Nancy Irvine, Rachel Geisthardt

Front Row: Michelle Smulders, Meredith Franden, Selna Harris, Aimee Remigo, Jennifer Lupinski, Sherene Smith, Carolyn Schwarz, Gia Biagi, Brenda Beaudry

School of Nursing Class of 2006

Top Row: Rebecca Adams, Leslie Babich, Katherine Banas, Lori Barnett, Stacey Bednarz, Kelly C Berryman, Adam Brieger, Tina Brown, Kimberly Burleigh, Anne Byrne, Julia Carl, Terra Caswell, Angela Chabot, Molly Colgan, Desiree Conyers, Amy Cook, Melissa Cooley, Ashley Cooper, Morgan Cornell

Row 2: Delphine Cornet, Laura Cortina, Casey Cox, Bradley Crow, Lauren D'Agostino, Katelyn Davis, Kara Dendrinos, Rachael Dunckel, Carolyn Ellis, Kristin Ellis

Row 3: Deonna French, Erin Gasser, Amanda George, Michelle Gilmore, Jacquelene Goyett, LaRonda Gracia, Tera Greenberg, Tracy Guzzardo, Amy Hamlin Tapper, Shawn Hathaway

Row 4: Jennifer Heller, Michele Hetfield, Hilary Heuer, Christen Hicks, unknown, Melissa Jenkins, Terri Jobkar, Jennifer Keller, Karissa Kerg, Katherine Kern

Row 5: Keri Kingma, Amanda Kristofik, Brigid Kutner, Melissa LaDuke, Lorraine Law, Katherine Lawler, Allison Ledtke, Corinne Lee

Row 6: Kerrie Lemerand, Kristen Maki, Smith Margaret, Cynthia Mathew, Thomas Mazzocco, Cara McAlpin

Row 7: Lana McCarthy, Erin McKeever, Nicolyn Meek, Patricia Coleman-Burns, Carol Loveland-Cherry, Judith Lynch-Sauer, Ada Sue Hinshaw, Barbara Guthrie, Marge Calarco, Carolyn Sampeselle, Joanne Pohl, Therese Messing, Rachel Milkowski, Renee Miller

Row 8: Andrea S Miller, Stephanie Mizer, Melissa Morgan, Heather Bidgoli, Elisa Brunetto, Jessica Cleghorn, Jade Curry, Ashley Dorow, Megan Finn, Lisa Gruen, Margaret Kelemen, Andrea Munger, Elizabeth Spencer, Mary Vanderweele, Abigail Vertalka, Jackelyn Ng, Phuong Nguyen, Gracia Nicolaescu

Row 9: Laura Norris, Elizabeth Osborn, Lavinia Pacurar, Carly Palmer, Kristine Parish, Jill Patterson, Mary Pepper, David Perout, Michael Pfeifer, Kristin Phillips, Susanne Pickman, Vanessa Polly, Sabrina Porter, Christina Quillan, Lauren Ramoie, Natasha Rivers, Teresa Roberts, Megan Robertson, Byanqa Robinson

Row 10: Mary Rodzik, Kimberly Sanders, Weber Sasha, Rebecca Scheiblauer, Taylor Schmidt, Jacquelyn Schrot, Tanya Shisler, Daniel Shivel, Sophia Shyu, Michelle Skurulsky, Melissa Smalligan, Erin Sorensen, Allison Spinweber, Lindsay Steiger, Natalya Stokely, Karen Stoneburner, Katherine Stout, Stephanie Swihart, Aaron Taylor

Row 11: Lori Thome, Christopher Thuer, Carolyn Trabka, Kathryn Trommbley, Valerie Tumbleson, Stacey Ventola, Dana Verkade, Caitlyn Vert, Angela Videto, Kari Wanless, Abby Wegener, Stephanie Westphal, Eric Williams, Whitney Zachritz, Amber Zemer, Joanna Zizzo, Chelsea Zussman

School of Nursing Class of 2009

Top Row: Allison Anderson, Meghan Archer, Christopher Aten, Meredith Bajor, Sarah Belleville, Kimberly Bergere, Courtney Bernier, Diana Blanks, Julie Bluhm, Melanie Bork, Karyn Braley, Kathryn Melody Briones, Christine Brouillard, Alyson Bryson

Row 2: Amy Burk, Kelly Capellari, Carmon Carlson, Krystal Cavaliere, Jeffrey Chiambretti, Christine Cho, Renee Christopher, Holli Clewis, James Conway, Kelly Courtney, Jenna Dahn, Erin Daly, Nicole DeFauw, Stefanie DeVita, Jessica DiVirgil, Debra Dombrowski, Genevieve Donnell

Row 3: Kathleen Donnelly, Jennifer El Aile, William Faulkner, Kimberly Johnson, Danielle Alameda, Margaret Wheeler, Brian D Kaminski Jr, Bridget Fil, Rochelle Weller, Leslie Allen-Huisman, Jennifer Musbach, Kathy Feig, Lori Fellows, Shana Ferguson

Row 4: Lauren Frawley, Ashton Frederick, Molly Gacetta, Stephanie Ganger, Amanda Garcia, Megan Gdowski, Chad Godfrey, Emily Halpern

Row 5: Katherine Hammons, Natalie Hecht, Danielle Hiltz, Taylor Hosner, Jennifer Huber, Holly Huling, Nathaniel Hunt, Ana-Leonor Jay

Row 6: Rachel Jeltema, Jennifer Jones, Lindsey Jones, Sarah Kaherl, Jessica Kehbein, Kendra Leidecker, Vanessa Lelli, Meghan Lemmer, Rachel Levinson, Alexandra Lindsay

Row 7: Amanda MacDonald, Joelle Marineau, Laura Mason, Andrea Masser, Michele McKinney, Charles-Robert Moultry, Kathleen Potempa, Bonnie Hagerty, Nicole Nader, Minna Navvab, Rachael Newnam, Uche Obua, Sara Oles, Ceren Onsan-Fitzpatrick

Row 8: Emily Parobek, Dorasy Paul, Rosalynne Pinga, Sarah Pope, Laura Randall, Sarah Reits, Emma Rew, Annemarie Rozwadowski, Nicole Ruhlman, Lydia Sanok, Grace Savercool, Kimberly Schmidt, Renee Schoenborn, Lisa Schuman, Kaitlyn Seltzer, Catherine Sherwood, Elizabeth Smith

Row 9: Aimee Surma, Stephanie Swinteck, Hanna Taylor, Donnie Tietsema, Andreea Toader, Stephanie Upplegger, Meghan Visnick, Scharnice Ward, Tabytha Whitley, Kimberly Wilke, Carie Wright, Kyleen Young, Kristin Zawacki, Christina Ziegler, Carlotta Zirker

Isolation of polymorphic tetranucleotide microsatellite markers in the satin bowerbird, Ptilonorhynchus violaceus

We isolated 13 polymorphic microsatellite markers from the satin bowerbird, Ptilonorhynchus violaceus from a genomic library enriched in (AAGG)(n) repetitive elements and characterized them in 20 individuals. The number of alleles ranged from two to 18 per locus with the observed heterozygosity ranging from 0.15 to 1.00. These markers will be useful for analysing questions concerning parentage, population genetic structure and models of speciation.

Syntaxin 6 and Vti1b form a novel SNARE complex, which is up-regulated in activated macrophages to facilitate exocytosis of tumor necrosis factor-alpha

A key function of activated macrophages is to secrete proinflammatory cytokines such as TNF alpha; however, the intracellular pathway and machinery responsible for cytokine trafficking and secretion is largely undefined. Here we show that individual SNARE proteins involved in vesicle docking and fusion are regulated at both gene and protein expression upon stimulation with the bacterial cell wall component lipopolysaccharide. Focusing on two intracellular SNARE proteins, Vti1b and syntaxin 6 (Stx6), we show that they are up-regulated in conjunction with increasing cytokine secretion in activated macrophages and that their levels are selectively titrated to accommodate the volume and timing of post-Golgi cytokine trafficking. In macrophages, Vti1b and syntaxin 6 are localized on intracellular membranes and are present on isolated Golgi membranes and on Golgi-derived TNF alpha vesicles budded in vitro. By immunoprecipitation, we find that Vti1b and syntaxin 6 interact to form a novel intracellular Q-SNARE complex. Functional studies using overexpression of full-length and truncated proteins show that both Vti1b and syntaxin 6 function and have rate-limiting roles in TNF alpha trafficking and secretion. This study shows how macrophages have uniquely adapted a novel Golgi-associated SNARE complex to accommodate their requirement for increased cytokine secretion.

Real-time reverse transcriptase PCR for the endogenous koala retrovirus reveals an association between plasma viral load and neoplastic disease in koalas

Koala retrovirus (KoRV) is a newly described endogenous retrovirus and is unusual in that inserts comprise a full-length replication competent genome. As koalas are known to suffer from an extremely high incidence of leukaemia/lymphoma, the association between this retrovirus and disease in koalas was examined. Using quantitative real-time reverse transcriptase PCR it was demonstrated that KoRV RNA levels in plasma are significantly increased in animals suffering from leukaemia or lymphoma when compared with healthy animals. Increased levels of KoRV were also seen for animals with clinical chlamydiosis. A significant positive association between viral RNA levels and age was also demonstrated. Real-time PCR demonstrated as much as 5 log variation in KoRV proviral DNA levels in genomic DNA extracted from whole blood from different animals. Taken together these data indicate that KoRV is an active endogenous retrovirus and suggests that it may be causally linked to neoplastic disease in koalas.

Unlocking pathology archives for molecular genetic studies: a reliable method to generate probes for chromogenic and fluorescent in situ hybridization

Chromogenic (CISH) and fluorescent ( FISH) in situ hybridization have emerged as reliable techniques to identify amplifications and chromosomal translocations. CISH provides a spatial distribution of gene copy number changes in tumour tissue and allows a direct correlation between copy number changes and the morphological features of neoplastic cells. However, the limited number of commercially available gene probes has hindered the use of this technique. We have devised a protocol to generate probes for CISH that can be applied to formalin-fixed, paraffin-embedded tissue sections (FFPETS). Bacterial artificial chromosomes ( BACs) containing fragments of human DNA which map to specific genomic regions of interest are amplified with phi 29 polymerase and random primer labelled with biotin. The genomic location of these can be readily confirmed by BAC end pair sequencing and FISH mapping on normal lymphocyte metaphase spreads. To demonstrate the reliability of the probes generated with this protocol, four strategies were employed: (i) probes mapping to cyclin D1 (CCND1) were generated and their performance was compared with that of a commercially available probe for the same gene in a series of 10 FFPETS of breast cancer samples of which five harboured CCND1 amplification; (ii) probes targeting cyclin-dependent kinase 4 were used to validate an amplification identified by microarray-based comparative genomic hybridization (aCGH) in a pleomorphic adenoma; (iii) probes targeting fibroblast growth factor receptor 1 and CCND1 were used to validate amplifications mapping to these regions, as defined by aCGH, in an invasive lobular breast carcinoma with FISH and CISH; and (iv) gene-specific probes for ETV6 and NTRK3 were used to demonstrate the presence of t(12; 15)(p12; q25) translocation in a case of breast secretory carcinoma with dual colour FISH. In summary, this protocol enables the generation of probes mapping to any gene of interest that can be applied to FFPETS, allowing correlation of morphological features with gene copy number.

SNAREing immunity: the role of SNAREs in the immune system

The trafficking of molecules and membranes within cells is a prerequisite for all aspects of cellular immune functions, including the delivery and recycling of cell-surface proteins, secretion of immune mediators, ingestion of pathogens and activation of lymphocytes. SNARE (soluble-N-ethylmaleimide-sensitive-factor accessory-protein receptor)-family members mediate membrane fusion during all steps of trafficking, and function in almost all aspects of innate and adaptive immune responses. Here, we provide an overview of the roles of SNAREs in immune cells, offering insight into one level at which precision and tight regulation are instilled on immune responses.

Objective grading of the anterior eye

Purpose. To convert objective image analysis of anterior ocular surfaces into recognisable clinical grades, in order to provide a more sensitive and reliable equivalent to current subjective grading methods; a prospective, randomized study correlating clinical grading with digital image assessment. Methods. The possible range of clinical presentations Of bulbar and palpebral hyperaemia, palpebral roughness and corneal staining were represented by 4 sets of 10 images. The images were displayed in random order and graded by 50 clinicians using both subjective CCLRU and Efron grading scales. Previously validated objective image analysis was performed 3 times oil each of the 40 images. Digital measures included edge-detection and relative-coloration components. Step-wise regression analysis determined correlations between the average subjective grade and the objective image analysis measures. Results. Average subjective grades Could be predicted by a combination of the objective image analysis components. These digital ``grades'' accounted for between 69%, (for Efron scale-graded palpebral redness) and 98% (for Efron scale-graded bulbar hyperaemia) of the subjective variance. Conclusions. The results indicate that clinicians may use a combination of vessel areas and overall hue in their judgment of clinical severity for certain conditions. Objective grading call take these aspects into account, and be used to predict an average ``objective grade'' to be used by a clinician in describing the anterior eye. These measures are more sensitive and reliable than subjective grading while still utilizing familiar terminology, and can be applied in research or practice to improve the detection, and monitoring of ocular surface changes.