tbuckley/cabot-search huggingface dataset:
Treatment Key to Reducing Cost of Crime
Authors: Bridget M. Kuehn
Journal: JAMA (2006)

Somatic treatments benefit some people whose depression persists after treatment with medication, psychotherapy, and a combination of these two, said Mark George, MD, professor of psychiatry and director of the brain stimulation laboratory at the Medical University of South Carolina, in Charleston. Refinements of electroconvulsive therapy that use a shorter pulse width yield efficacy comparable with older techniques, with less cognitive dysfunction, George said. In 2005, the US Food and Drug Administration approved vagus nerve stimulation for treatment-resistant depression. This technique requires implantation of a pacemaker in the neck to stimulate the left vagus nerve. Repetitive transcranial magnetic stimulation (rTMS) has generated the most excitement among researchers in therapeutic neuromodulation, George said, as rTMS is non-invasive, and, in studies to date, has not been shown to have deleterious cognitive effects. This still-investigative technique involves external application of magnetic fields that stimulate the cortex. A 20-site study of 301 patients with difficult-to-treat depression who received either rTMS or sham rTMS as outpatients for 35 min/d, 5 d/wk, for up to 6 weeks, followed by a 3-week taper phase, found greater improvement on standard depression rating scales in the active treatment group than in the sham treatment group, according to a report at another symposium at the Toronto meeting. John O’Reardon, MD, assistant professor of psychiatry at the University of Pennsylvania School of Medicine, Philadelphia, principal investigator at that site, described findings from this study, funded by Neuronetics Inc, a TMS device manufacturer. A replication trial sponsored by the National Institutes of Health is now in progress.
Alternatively and Constitutively Spliced Exons Are Subject to Different Evolutionary Forces
Authors: Feng-Chi Chen, Sheng-Shun Wang, Chuang-Jong Chen, Wen-Hsiung Li, Trees-Juen Chuang
Journal: Molecular Biology and Evolution (2005)

There has been a controversy on whether alternatively spliced exons (ASEs) evolve faster than constitutively spliced exons (CSEs). Although it has been noted that ASEs are subject to weaker selective constraints than CSEs, so they evolve faster, there have also been studies that indicated slower evolution in ASEs than in CSEs. In this study, we retrieve more than 5,000 human-mouse orthologous exons and calculate the synonymous (KS) and nonsynonymous (KA) substitution rates in these exons. Our results show that ASEs have higher KA values and higher KA/KS ratios than CSEs, indicating faster amino acid–level evolution in ASEs. The faster evolution may be in part due to weaker selective constraints. It is also possible that the faster rate is in part due to faster functional evolution in ASEs. On the other hand, the majority of ASEs have lower KS values than CSEs. With reference to the substitution rate in introns, we show that the KS values in ASEs are close to the neutral substitution rate, whereas the synonymous substitution rate in CSEs has likely been accelerated. The elevated synonymous rate in CSEs is not related to CpG dinucleotides or low-complexity regions of protein but may be weakly related to codon usage bias. The overall trends of higher KA and lower KS in ASEs than in CSEs are also observed in human-rat and mouse-rat comparisons. Therefore, our observations hold for mammals of different molecular clocks.
Severe Acute Respiratory Syndrome and Influenza
Authors: Kennedy F. Shortridge
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The eminent sinologist and historian, Joseph Needham, writing with his colleague Lu Gwei-Djen in the sixth volume of his mighty tome “Science and Civilization in China,” emphasized the long held Chinese conviction that “the best medicine is preventive medicine,” a conviction that goes back to the Warring States period (475–221 B.C.) when there was a flowering of philosophy and medical understanding. A Han Dynasty (206 B.C.–220 A.D.) writing concludes “A skillful doctor cures illness when there is no sign of disease, and thus the disease never comes” (1, 2). This component of the “Chinese Hippocratic Corpus,” as Needham calls it, holds just as true in today’s modern world and may be simply summed-up in one word: “awareness.” In the case of emerging infectious disease, this means “preparedness,” giving rise to “reaction.” Two thousand or so years onward in the China of today, this conviction is being sorely tested by nature with incursions of respiratory viruses from its southeastern province of Guangdong adjacent to Hong Kong. In 1997, the world was thrown into a state of alarm and high alert arising from the emergence of a potentially new influenza pandemic caused by the transmission of a highly pathogenic H5N1 influenza virus (H5N1/97) of avian origin from chickens to humans in Hong Kong (3–5). On that occasion, a pandemic was only one or two mutational events away. H5N1-like viruses were recognized in chicken and other land-based poultry in Hong Kong in 2001 and 2002 before they could infect humans (6, 7). Probably three or four mutational events from generating a pandemic influenza virus, these more recent incidents upheld the ancient ideal of preventing disease before it appears. In these cases the virus did not “escape” from Hong Kong almost certainly because of its having had sound human and animal disease and virus surveillance systems in place for some time. This led to the recognition of the source of the virus and its removal by the slaughter of poultry in live markets and on farms, or a combination of slaughter and ring vaccination on farms (6–8). Over the years, Hong Kong essentially functioned as an influenza sentinel post for the wider region, stemming from the
Sarco/Endoplasmic Reticulum Ca <sup>2+</sup> -ATPase Gene Transfer Reduces Vascular Smooth Muscle Cell Proliferation and Neointima Formation in the Rat
Authors: Larissa Lipskaia, Federica del Monte, Thierry Capiod, Sabrina Yacoubi, Lahouaria Hadri, Michel Hours, Roger J. Hajjar, Anne-Marie Lompré
Journal: Circulation Research (2005)

Proliferation of vascular smooth muscle cells (VSMC) is a primary cause of vascular disorders and is associated with major alterations in Ca2+ handling supported by loss of the sarco/endoplasmic reticulum calcium ATPase, SERCA2a. To determine the importance of SERCA2a in neointima formation, we have prevented loss of its expression by adenoviral gene transfer in a model of balloon injury of the rat carotid artery. Two weeks after injury, the intima/media ratio was significantly lower in SERCA2a-infected than in injured noninfected or injured beta-galactosidase-infected carotids (0.29+/-0.04 versus 0.89+/-0.19 and 0.72+/-0.14, respectively; P<0.05), and was comparable to that observed in control carotids (0.21+/-0.03). The pathways leading to proliferation were analyzed in serum-stimulated VSMC. Forced expression of SERCA2a arrested cell cycle at the G1 phase and prevented apoptosis. SERCA2a inhibits proliferation through inactivation of calcineurin (PP2B) and its target transcription factor NFAT (nuclear factor of activated T-cells) resulting in lowering of cyclin D1 and pRb levels. By using NFAT-competing peptide VIVIT, we showed that NFAT activity is strongly required to promote VSMC proliferation. In conclusion, we provide the first evidence that increasing SERCA2a activity inhibits VSMC proliferation and balloon injury-induced neointima formation.
Functional Reprogramming of the Primary Immune Response by T Cell Receptor Antagonism
Authors: Dipica Haribhai, Brandon Edwards, Mary L. Williams, Calvin B. Williams
Journal: The Journal of Experimental Medicine (2004)

The T cell receptor must translate modest, quantitative differences in ligand binding kinetics into the qualitatively distinct signals used to determine cell fate. Here, we use mice that express an endogenous T cell receptor (TCR) antagonist and an adoptive transfer system to examine the influence of TCR signal quality on the development of effector function. We show that activation of antigen-specific T cells in the presence of an antagonist results in a functional reprogramming of the primary immune response, marked by altered T cell homing, a failure to develop effector function, and ultimately clonal elimination by apoptosis. Importantly, antagonism does not block cell division, implying that the signals promoting clonal expansion and effector differentiation are distinct.
Genetic regulation of the antibody response to H-2Db alloantigens in mice. II. Tolerance to non-H-2 determinants abolishes the antibody response to H-2Db in B10.A(5R) mice.
Authors: D Wernet, F Lilly
Journal: The Journal of Experimental Medicine (1976)

B10.A(5R) mice (H-2i5), immunized with spleen cells from congenic B10 mice (H-2b), responded to alloantigens of the H-2Db region by producing antibodies of only IgM type. In contrast, they produced both IgM and IgG antibodies when immunized with noncongenic H-2b cells that carry other foreign cell surface antigens (non-H-2) in addition to H-2Db. A hypothesis was proposed comparing the H-2Db antigen on a congenic cell to a hapten on a nonimmunogenic carrier which fails to induce T-cell helper function responsible for the switch from IgM to IgG secretion in B cells. Data presented here confirmed this hypothesis. 5R mice rendered tolerant to the relevant non-H-2 antigens were unable to mount the anti-H-2Db IgG response in a noncongenic immunization. Tolerance induction did not lead to abrogation of the T-cell mediated cytotoxicity.
THE NATURE OF THE VIRUS RECEPTORS OF RED CELLS
Authors: George K. Hirst
Journal: The Journal of Experimental Medicine (1948)

Evidence has been offered that influenza virus which has been heated at 56 degrees C. for 30 or more minutes loses some of its capacity to agglutinate red cells and may completely lose its power to elute from cells on which it has been adsorbed. Such heat-inactivated virus does not possess the capacity to destroy the virus inhibitor in normal rabbit serum and this appears to be the explanation of the higher agglutinin inhibitory levels obtained with serum and heated virus as compared with serum and untreated virus. The heat-inactivated virus can be used to measure the inhibitor substance in normal rabbit serum. By two different methods it has been demonstrated that the inhibitor is destroyed in the presence of unheated influenza virus, as measured by inhibition titrations with virus inactivated at 56 degrees C. The destruction of inhibitor by virus of either type A or B can be measured by virus of either type with similar results.
Revalidation of doctors in Canada
Authors: W D. Dauphinee
Journal: BMJ (1999)

Editorial by Buckley 

All approaches to revalidation ask doctors to prove their continuing competence to practise. This paper considers developments in Canada from two perspectives: what the profession and its regulatory bodies are doing to meet the challenge of maintaining doctors' performance, and the methods of assessment the regulatory bodies and agencies are using to address this issue. The two perspectives have led to two primary pathways: assessment related to practice activities but linked to an educational or enhancement feedback by the licensing bodies, and strategies emphasising the maintenance of good learning practices by the certifying bodies. The term revalidation is not widely used in Canada, but it can be defined as enforcing standards of practice in the medical workplace by direct measures of doctors' performance.

We reviewed the peer reviewed literature and publicly available documents describing either existing or proposed steps for the revalidation of medical licensure or certification and the maintenance of good medical learning practices in Canada. This generated a summary of the principal developments in policy and technical aspects, including a discussion of emerging challenges.

Canada is a federation of 10 provinces and three territories. Health care is the responsibility of the provinces and territories. Though licensure of health professionals is a provincial matter, nationwide entry standards exist and are administered by national bodies: the Medical Council of Canada (basic medical qualifications) and the Royal College of Physicians and Surgeons of Canada (specialists) and the College of Family Physicians of Canada (family medicine). These are recognised by all jurisdictions but one.1 National standards for the accreditation of hospitals exist, and provinces can participate in quality control through budgetary and utilisation reviews.

### Peer review mechanisms

The medical licensing authorities have been monitoring doctors' practices for many years For example, Canada's three most populated provinces, British Columbia, Ontario, and Quebec, …
Heterogeneity of Regional Redox Status and Relation of the Redox Status to Oxygenation in a Tumor Model, Evaluated Using Electron Paramagnetic Resonance Imaging
Authors: Keizo Takeshita, Kumiko Kawaguchi, Kaori Fujii-Aikawa, Megumi Ueno, Shoko Okazaki, Mitsuhiro Ono, Murali C. Krishna, Periannan Kuppusamy, Toshihiko Ozawa, Nobuo Ikota
Journal: Cancer Research (2010)

It is widely accepted that redox status, along with the partial pressure of oxygen (pO(2)), determines the efficacy of some therapeutic methods applied to treat tumors, including radiation. Redox status, evaluated by the reduction of a nitroxyl probe, was reportedly heterogeneous in a mouse tumor model. However, neither variation of heterogeneity of the redox status among mice nor the relation of the redox status to pO(2) in tumors has been characterized sufficiently. In this study, the regional reduction status in a mouse radiation-induced fibrosarcoma tumor model was evaluated using sequential three-dimensional electron paramagnetic resonance (EPR) imaging after i.v. injection of a tissue-permeable nitroxyl probe, HM-PROXYL. The regional decay of HM-PROXYL signal obeyed first-order kinetics, and the amplitude of the reduction rate and extent of its heterogeneity in a tumor varied among six mice. The tissue pO(2) was measured using EPR oximetry with lithium phthalocyanine (LiPc) microcrystals implanted within the tumor. The location of LiPc was determined with EPR imaging. A sequential image was obtained following the injection of HM-PROXYL, even after LiPc implantation, by choosing an HM-PROXYL signal peak which does not overlap with the signal of LiPc. The relationship between pO(2) and the reduction rate at the region of pO(2) measurement was found to be low (r = 0.357) in 13 tumor-bearing mice, indicating that the extent of oxygenation does not necessarily affect the redox status under air-breathing conditions. The results strongly indicate the necessity of measurements of both redox status and oxygenation in every tumor to characterize tumor physiology.
Legionnaires' Disease Associated with a Hospital Water System: A Cluster of 24 Nosocomial Cases
Authors: CHARLES M. HELMS
Journal: Annals of Internal Medicine (1983)

Over a 10-month period, 24 cases of Legionnaires' disease pneumonia occurred among patients admitted to an Iowa hospital, most of whom were immunosuppressed. Eleven patients died. Twenty-one patients were admitted to a recently completed hospital addition, 16 of these to a new hematology-oncology unit. Legionella pneumophila serogroup 1 was isolated from the patients, water outlets, and hot water in the new addition. Water quality variables in the hospital addition were adequate. Shock chlorination, temporary elevation of the hot water temperature, and continuous chlorination of hospital water decreased the frequency of isolation of Legionella. Water use by patients in the hematology-oncology unit was restricted until the water was free of Legionella. The incidence of Legionnaires' disease decreased. Indirect evidence supports an hypothesis of water-borne disease in this cluster of cases. Current variables of acceptable water potability may not guarantee water free of L. pneumophila.
Axon Sorting in the Optic Tract Requires HSPG Synthesis by ext2 (dackel) and extl3 (boxer)
Authors: Jeong-Soo Lee, Sophia von der Hardt, Melissa A. Rusch, Sally E. Stringer, Heather L. Stickney, William S. Talbot, Robert Geisler, Christiane Nüsslein-Volhard, Scott B. Selleck, Chi-Bin Chien, Henry Roehl
Journal: Neuron (2004)
Timing and sequence of differentiation of embryonic rat hepatocytes along the biliary epithelial lineage
Authors: Robbert G.E. Notenboom, Marius A. van den Bergh Weerman, Koert P. Dingemans, Jacqueline L.M. Vermeulen, Stefan van den Eijnde, Chris P. Reutelingsperger, Hans Hut, Rob Willemsen, Johan G.A. Offerhaus, Wouter H. Lamers
Journal: Hepatology (2003)

To study the differentiation of hepatocytes along the biliary epithelial lineage in vivo, embryonic day 14 (E14) rat hepatocytes were isolated by differential centrifugation and transplanted as single-cell suspensions into the spleen of adult syngeneic rats. Hepatocytes and cholangiocytes were identified and their maturation characterized by the level of expression of alpha-fetoprotein (AFP), glutamate dehydrogenase (GDH), and carbamoyl phosphate synthetase I (CPS); annexin IV, annexin V, cytokeratin 19 (CK-19), and cystic fibrosis transmembrane conductance regulator (CFTR); and electron microscopy. By correlating morphologic changes with the timing in the expression of these markers, we show that the organization of the transplanted E14 hepatocytes into lobular structures is accompanied by the formation and maturation of bile ducts around these developing lobules. Morphologic differentiation of the emerging bile ducts was accompanied by a gradual loss of hepatocyte markers and a gradual acquisition of cholangiocyte markers, with markers identifying a large-cholangiocyte phenotype appearing latest. Once fully differentiated, the intrasplenic liver lobules developed cholestatic features. The accompanying proliferation of bile ducts was due to cholangiocyte proliferation, but ductular transformation of hepatocytes was also observed. In conclusion, (1) bile duct formation at the interface between hepatocytes and connective tissue is an inherent component of liver development and (2) the susceptibility of developing hepatocytes to bile duct-inducing signals is highest in the fetal liver but that (3) this capacity is not irreversibly lost in otherwise mature hepatocytes.
Latent Herpesviruses of Humans
Authors: M. COLIN JORDAN
Journal: Annals of Internal Medicine (1984)

The herpesviruses that infect humans characteristically establish a latent infection that may be reactivated later. The consequences of reactivation range from asymptomatic shedding to severe disseminated infection. Varicella-zoster and herpes simplex viruses are both highly neurotropic, establishing nonreplicating infections in sensory ganglia. Latent herpes simplex virus is known to reside in neurons, and the virus-cell interactions involved have been defined to an extent. Cytomegalovirus and Epstein-Barr virus interact with peripheral blood leukocytes. Latent cytomegalovirus infection of human leukocytes has not been proved, although studies in a murine model have implicated B lymphocytes as a repository of latent virus. Epstein-Barr virus is known to persist in a non-replicating state as extrachromosomal DNA in B lymphocytes and to cause "immortalization" of the infected cell; persistence of the viral genome in epithelial cells may also result in malignant transformation, such as nasopharyngeal carcinoma.
Atorvastatin Inhibits Hypercholesterolemia-Induced Calcification in the Aortic Valves via the Lrp5 Receptor Pathway
Authors: Nalini M. Rajamannan, Malayannan Subramaniam, Frank Caira, Stuart R. Stock, Thomas C. Spelsberg
Journal: Circulation (2005)

Background— Calcific aortic valve disease is the most common indication for surgical valve replacement in the United States. The cellular mechanisms of valve calcification are not well understood. We have previously shown that cellular proliferation and osteoblastogenesis are important in the development of valvular heart disease. Lrp5, a known low-density receptor-related protein, plays an essential role in cellular proliferation and osteoblastogenesis via the β-catenin signaling pathway. We hypothesize that Lrp5 also plays a role in aortic valve (AV) calcification in experimental hypercholesterolemia. Methods and Results— We examined the effects of cholesterol and atorvastatin in Watanabe rabbits (n=54). Group I (n=18) received a normal diet, group II (n=18) a 0.25% cholesterol diet, and group III (n=18) a 0.25% (w/w) cholesterol diet with atorvastatin for the development of calcification. The AVs were examined for cellular proliferation, Lrp5/β-catenin, and bone matrix markers. Bone formation was assessed by micro-computed tomography, calcein injection, and osteopontin expression. Low-density lipoprotein with and without atorvastatin was also tested in AV myofibroblasts for cellular proliferation and regulation of the Lrp5/β-catenin pathway. Our results demonstrate that the cholesterol diet induced complex bone formations in the calcified AVs with an increase in the Lrp5 receptors, osteopontin, and p42/44 expression. Atorvastatin reduced bone formation, cellular proliferation, and Lrp5/β-catenin protein levels in the AVs. In vitro analysis confirmed the Lrp5/β-catenin expression in myofibroblast cell proliferation. Conclusion— Hypercholesterolemic AV calcification is attenuated by atorvastatin and is mediated in part by the Lrp5/β-catenin pathway. This developmental pathway may be important in the signaling pathway of this disease.
TrpC1 Is a Membrane-Spanning Subunit of Store-Operated Ca <sup>2+</sup> Channels in Native Vascular Smooth Muscle Cells
Authors: Shang-Zhong Xu, David J. Beech
Journal: Circulation Research (2001)

Mammalian counterparts of the Drosophila trp gene have been suggested to encode store-operated Ca(2+) channels. These specialized channels are widely distributed and may have a general function to reload Ca(2+) into sarcoplasmic reticulum as well as specific functions, including the control of cell proliferation and muscle contraction. Heterologous expression of mammalian trp genes enhances or generates Ca(2+) channel activity, but the crucial question of whether any of the genes encode native subunits of store-operated channels remains unanswered. We have investigated if TrpC1 protein (encoded by trp1 gene) is a store-operated channel in freshly isolated smooth muscle cells of resistance arterioles, arteries, and veins from human, mouse, or rabbit. Messenger RNA encoding TrpC1 was broadly expressed. TrpC1-specific antibody targeted to peptide predicted to contribute to the outer vestibule of TrpC1 channels revealed that TrpC1 is localized to the plasma membrane and has an extracellular domain. Peptide-specific binding of the antibody had a functional effect, selectively blocking store-operated Ca(2+) channel activity. The antibody is a powerful new tool for the study of mammalian trp1 gene product. The study shows that TrpC1 is a novel physiological Ca(2+) channel subunit in arterial smooth muscle cells.