tbuckley/cabot-search huggingface dataset:
The Extraction of 3D Shape in the Visual System of Human and Nonhuman Primates
Authors: Guy A. Orban
Journal: Annual Review of Neuroscience (2011)

Depth structure, the third dimension of object shape, is extracted from disparity, motion, texture, and shading in the optic array. Gradient-selective neurons play a key role in this process. Such neurons occur in CIP, AIP, TEs, and F5 (for first- or second-order disparity gradients), in MT/V5, in FST (for speed gradients), and in CIP and TEs (for texture gradients). Most of these regions are activated during magnetic resonance scanning in alert monkeys by comparing 3D conditions with the 2D controls for the different cues. Similarities in activation patterns of monkeys and humans tested with identical paradigms suggest that like gradient-selective neurons are found in corresponding human cortical areas. This view gains credence as the homologies between such areas become more evident. Furthermore, 3D shape-processing networks are similar in the two species, with the exception of the greater involvement of human posterior parietal cortex in the extraction of 3D shape from motion. Thus we can begin to understand how depth structure is extracted from motion, disparity, and texture in the primate brain, but the extraction of depth structure from shading and that of wire-like objects requires further scrutiny.
Alcohol drinking and bladder cancer risk: a meta-analysis
Authors: C. Pelucchi, C. Galeone, I. Tramacere, V. Bagnardi, E. Negri, F. Islami, L. Scotti, R. Bellocco, G. Corrao, P. Boffetta, C. La Vecchia
Journal: Annals of Oncology (2011)
The Effect of Intermittent Positive Pressure Breathing on the Lung Compliance and Intrapulmonary Mixing of Gases
Authors: P. A. Emerson, G. E. Torres, H. A. Lyons
Journal: Thorax (1960)

Nims, Conner, and Comroe (1955) found that the compliance of the whole chest was smaller in anaesthetized than in conscious subjects; they suggested that this was probably due to the inability of the conscious subject to relax the muscles of inspiration.Howell and Peckett (1957) confirmed these findings, but pointed out that the compliance was being measured in different ways.In the conscious subject the inflating mechanism was the expanding action of the inspiratory muscles, whereas in positive pressure breathing the pattern of inflation of the lungs was no longer solely dependent on the changing shape of the thoracic cage.In these circumstances the two components of the thorax, the lungs and thoracic wall with the diaphragm, now represented a single visco-elastic resistance to the inflating pressure, and the pattern of inflation of the thorax depended on the magnitude and distribution of the com- bined resistances and might result in a different distribution of the inspired volume.They suggested that positive pressure breathing might result in over-distension of some areas of lung and under-ventilation of others.This would result in a lower effective volume of lung being inflated, and the compliance measured under such circum- stances would be lower than that of the same lung when naturally and evenly inflated by the action of the respiratory muscles.In support of this theory they quoted their observations (Howell and Peckett, 1957) of values for lung compliance in 15 normal subjects using positive pressure methods.They drew attention to the larger values obtained with normal pressure methods in other patients by other workers, but when they measured the lung compliance in the same patients, first with normal pressure methods while conscious and later with positive pressure methods while paralysed and anaesthetized, the differences were much less than they expected (154 ml.conscious, 109 ml.paralysed, per cm. of water pressure).
Selectivity of Connexin-Specific Gap Junctions Does Not Correlate With Channel Conductance
Authors: Richard D. Veenstra, Hong-Zang Wang, Dolores A. Beblo, Mark G. Chilton, Andrew L. Harris, Eric C. Beyer, Peter R. Brink
Journal: Circulation Research (1995)

Abstract Connexins form a variety of gap junction channels that vary in their developmental and tissue-specific levels of expression, modulation of gating by transjunctional voltage and posttranslational modification, and unitary channel conductance (γ j ). Despite a 10-fold variation in γ j , whether connexin-specific channels possess distinct ionic and molecular permeabilities is presently unknown. A major assumption of the conventional model for a gap junction channel pore is that γ j is determined primarily by pore diameter. Hence, molecular size permeability limits should increase and ionic selectivity should decrease with increasing channel γ j (and pore diameter). Equimolar ion substitution of 120 mmol/L KCl for potassium glutamate was used to determine the unitary conductance ratios for rat connexin40 and connexin43, chicken connexin43 and connexin45, and human connexin37 channels functionally expressed in communication-deficient mouse neuroblastoma (N2A) cells. Comparison of experimental and predicted conductance ratios based on the aqueous mobilities of all ions according to the Goldman-Hodgkin-Katz current equation was used to determine relative anion-to-cation permeability ratios. Direct correlation of junctional conductance with dye transfer of two fluorescein-derivatives (2 mmol/L 6-carboxyfluorescein or 2′,7′-dichlorofluorescein) was also performed. Both approaches revealed a range of selectivities and permeabilities for all five different connexins that was independent of channel conductance. These results are not consistent with the conventional simple aqueous pore model of a gap junction channel and suggest a new model for connexin channel conductance and permselectivity based on electrostatic interactions. Divergent conductance and permeability properties are features of other classes of ion channels (eg, Na + and K + channels), implying similar mechanisms for selectivity.
Results of a Phase II Double-Blinded Randomized Clinical Trial of Difluoromethylornithine for Cervical Intraepithelial Neoplasia Grades 2 to 3
Authors: Anne-Thérèse Vlastos, Loyd A. West, E. Neely Atkinson, Iouri Boiko, Anais Malpica, Waun K. Hong, Michele Follen
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Our purpose was to conduct a double-blinded randomized trial of difluoromethylornithine (DFMO) at 0.125, 0.5 gm/m2, versus placebo in the treatment of cervical intraepithelial neoplasia (CIN) grades 2 to 3. A promising phase I study has shown histopathologic responses at these dose levels. Experimental Design: Patients with histopathologically confirmed CIN 2-3 lesions were recruited from a colposcopy clinic and underwent Papanicolaou testing, human papillomavirus testing, and colpophotography. They took oral contraception and DFMO or placebo elixir for 28 days and filled out the National Cancer Institute common toxicity calendars. They returned for follow-up and a repeat Papanicolaou smear, colpophotograph, and loop excision of the cervix. Results: There were no statistically significant differences among the arms in histopathologic response. This could no be explained by any biases in risk factors. The prominent toxicities were diarrhea, dizziness, nausea, and headaches. There were no differences in the toxicities among arms. The Papanicolaou smear was a poor biomarker of response and correlated poorly with the histopathology. Conclusions: DFMO is no active at 0.125 and 0.5 gm/m2 for 28 days when given orally in CIN 2-3. Higher oral doses or longer administration is necessary, supporting data from breast trials. Alternatively, a trial of topical DFMO might merit attention as activity has been noed in trials of actinic keratoses.
Variations In The FLG2 Gene Are Associated With Eczema Herpeticum In Populations Of European And African Descent
Authors: N.M. Rafaels, D.Y. Leung, L. Beck, P.S. Gao, M. Campbell, M. Boguniewicz, T. Hata, L. Schneider, J. Hanifin, R. Gallo, L. Gao, T.H. Beaty, K.C. Barnes
Journal: Journal of Allergy and Clinical Immunology (2011)
Relationship Between Depth of Response and Outcome in Multiple Myeloma
Authors: David Dingli, Jorge M. Pacheco, Grzegorz S. Nowakowski, Shaji K. Kumar, Angela Dispenzieri, Suzanne R. Hayman, Martha Q. Lacy, Dennis A. Gastineau, Morie A. Gertz
Journal: Journal of Clinical Oncology (2007)

Purpose High-dose therapy with autologous stem-cell transplantation (HDT-ASCT) is now almost standard therapy for many patients with multiple myeloma, partly because of higher complete response (CR) rates. Some studies suggest that tandem transplantation gives superior results. The aim of this study was to determine whether the depth of the response to HDT-ASCT leads to an improvement in time to progression (TTP) and overall survival (OS). We hypothesized that patients with CR before HDT-ASCT (BCR) will have their disease burden reduced further and experience a longer TTP and perhaps OS. Patients and Methods All patients who achieved BCR or CR after HDT-ASCT (ACR) were identified. The characteristics and long-term outcome of these patients were evaluated. Results We identified 14 patients with BCR and 103 patients with ACR who were treated in similar fashion. The patients have been followed for more than 6 years, and the median for OS has not been reached (60-month survival, 55% for BCR and 63% for ACR; P = .83). The median TTP was 43 months for BCR and 34 months for ACR (P = .39). Conclusion The depth of the response in myeloma does not necessarily lead to an improvement in TTP and OS. Tumor dynamics considerations show that the yield from sequential cycles of chemotherapy decreases. Patients who achieve CR with the first transplant can be safely observed without jeopardizing OS.
Observations concerning the binding of thyroid hormones in sera of normal subjects of varying ages.
Authors: L W Braverman, N A Dawber, S H Ingbar
Journal: Journal of Clinical Investigation (1966)

In man, from childhood through senescence, there occur alterations in several metabolic func- tions that are regulated in part by the thyroid hor- mones.Thus, aging is associated with a decrease in basal oxygen consumption per unit surface area and an increase in total serum cholesterol and beta-lipoprotein cholesterol (1-5).Several in- dexes of thyroid function per se indicate greater thyroid activity in children and adolescents than in young adults and, conversely, less thyroid ac- tivity in the elderly.The extensive literature on this subject has been considered in recent publica- tions (6, 7).It has been suggested, therefore, that there exist in childhood and senescence states of physiologic hyperand hypothyroidism, re- spectively (4, 6, 8).It is not clear, however, whether this is truly the case.In this regard it may be significant that, in contrast to the situation in clinically recognizable thyroid disease, the se- rum protein-bound iodine (PBI) varies little, if at all, throughout the life-span of man (6, 9, 10).Recent studies related to these questions have indicated that the fractional rate of turnover of thy- roxine (T4) in peripheral tissues decreases sig- nificantly from childhood through senescence (6, 8, 10-12).Since variations in the binding of thy- roid hormones to extracellular proteins greatly in- fluence the kinetics of hormonal metabolism (13-15), the present studies were undertaken to de- termine whether the changes in the metabolism of T4 that accompany aging can be ascribed to
Improved Insulin Sensitivity and Metabolic Control in Type 2 Diabetes Does Not Influence Plasma Homocysteine
Authors: Marie-Jose J. Pouwels, Martin den Heijer, Henk J. Blom, Cees J. Tack, Ad R. Hermus
Journal: Diabetes Care (2003)

Type 2 diabetes is characterized by both insulin resistance and an increased cardiovascular mortality (1). Elevated plasma total homocysteine levels are an independent risk factor for cardiovascular disease (2). Also, in patients with type 2 diabetes, elevated plasma total homocysteine levels are associated with an increased risk of cardiovascular disease and an increased mortality (3,4).

It is well known that insulin resistance is aggravated by chronic hyperglycemia. This hyperglycemia-induced insulin resistance is reversed by treatment, resulting in a prolonged period of euglycemia (5).

Although in animal studies evidence was found that hyperinsulinemia and/or insulin resistance increased total homocysteine levels (6), in humans the relation between insulin resistance and total homocysteine levels is unclear, in both healthy subjects (7–12) and patients with type 2 diabetes (13–16). In patients with type 2 diabetes, a positive association between insulin resistance and total homocysteine levels was reported (13), but this finding was not reproduced (14). Furthermore, in patients with …
The significance of bone marrow involvement in non-Hodgkin's lymphoma: the Eastern Cooperative Oncology Group experience.
Authors: J M Bennett, K C Cain, J H Glick, G J Johnson, E Ezdinli, M J O'Connell
Journal: Journal of Clinical Oncology (1986)

Data from four clinical trials conducted by the Eastern Cooperative Oncology Group (ECOG) were used to investigate the importance of bone marrow involvement as a prognostic factor in patients with non-Hodgkin's lymphoma (NHL). A total of 502 patients, 275 with nodular, poorly differentiated lymphocytic lymphoma (NLPD) and 227 with diffuse histiocytic lymphoma (DHL) or diffuse mixed-cell lymphoma (DML), were included in this analysis. Patients were separated into four categories: stage III, stage IV with bone marrow involvement (stage IV-M), stage IV without marrow involvement (stage IV-O), and stage IV with bone marrow and other organ involvement (stage IV-OM). Among the DHL and DML patients, the incidence of marrow involvement was 23%. However, stage IV-M patients had a prognosis that is similar to stage IV-O and stage IV-OM and worse than stage III patients. In contrast, the incidence of involvement with NLPD was 59% and patients with stage IV-M had a survival not different than stage III and not worse than stage IV-O and stage IV-OM. The results suggest that the current emphasis on bone marrow biopsy(s) as a routine diagnostic staging procedure for patients with NHL should be reevaluated. The necessity for this procedure in stage III patients with NLPD is not apparent from our data. One can still justify a bone marrow biopsy in stage I and II patients and can confirm the complete clinical response when all nodes have regressed in more advanced disease.
Readily Available Tissue-Engineered Vascular Grafts
Authors: Shannon L. M. Dahl, Alan P. Kypson, Jeffrey H. Lawson, Juliana L. Blum, Justin T. Strader, Yuling Li, Roberto J. Manson, William E. Tente, Louis DiBernardo, M. Taylor Hensley, Riley Carter, Tiare P. Williams, Heather L. Prichard, Margaret S. Dey, Keith G. Begelman, Laura E. Niklason
Journal: Science Translational Medicine (2011)

Nonimmunogenic, tissue-engineered vascular grafts stored long-term maintain their patency, strength, and function after transplant in large-animal models.
Characterizing T cell responses associated with hypersensitivity pneumonitis in pigeon fanciers
Authors: A. Jozwik, Nirupma Kakkar, O. Sparagano, Stephen Burke, Charles McSharry, Stephen Todryk
Journal: European Respiratory Journal (2012)

Background:   Around 10% of pigeon fanciers are affected by a form of hypersensitivity pneumonitis known as pigeon fanciers9 lung (PFL). PFL is an aberrant inflammatory immune response to dust particles that contain pigeon antigens, inhaled during pigeon husbandry, and manifests in fever and dyspnoea. A lymphocytic infiltrate has been observed in lung biopsies and bronchoalveolar lavage as well as Th1 cytokines. However, little is known about the implicated pathogenic T cells and whether a systemic response can be measured that indicates disease presence or severity.   Methods:   Disease history and blood samples were taken from 72 pigeon fanciers at a local pigeon show, 36.1% of whom had PFL. Effector T cell responses were examined by ELIspot.   Results:   All pigeon fanciers showed an Interferon (IFN)gamma response against antigens in pigeon serum regardless of possessing PFL, and there was no difference in magnitude of response between the groups.  No pigeon-specific IL-4, IL-5 or IL-17 ELIspot responses could be detected in any individual.  CFSE dilution demonstrated proliferation of CD4 cells in response to pigeon antigen that also possessed CD49d, a potential lung-homing integrin.  Interestingly, the IFNg ELIspot response could not be inhibited by anti-MHC class II antibody.   Conclusion:   These findings show that an unconventional T cell response is generated in conjunction with pulmonary exposure to pigeon antigens that may be necessary but not sufficient to cause PFL disease, and so further analysis of these cells is warranted.
Lithium for Zidovudine-Induced Neutropenia in AIDS
Authors: Victor Herbert
Journal: JAMA (1988)

To the Editor.—  In the June 17 issue, Erice et al1report the usual approach to zidovudine-induced neutropenia: reduce the dose. There may be an alternate approach: treat with lithium, in doses used to treat mood disorders, without or in addition to reducing the dose of zidovudine. This may be particularly important if others confirm that acute meningoencephalitis may occur from increased human immunodeficiency virus type 1 (HIV-1) replication after reduction of the dose of zidovudine.2  Ever since we discovered that lithium induces granulopoiesis3and the evidence that it stimulates a pluripotent stem cell,3,4it has been used to treat neutropenias.4We recently found it could stimulate helper (T4) lymphocyte production in acquired immunodeficiency syndrome (AIDS).5Subsequently, an AIDS patient took 1200 mg/d of zidovudine and, during the next three months, his leukocyte count (and fraction of neutrophils) fell from 4.7 × 109
Birth, Death, and Replacement of Karyopherins in Drosophila
Authors: N. Phadnis, E. Hsieh, H. S. Malik
Journal: Molecular Biology and Evolution (2011)

Nucleocytoplasmic transport is a broadly conserved process across eukaryotes. Despite its essential function and conserved mechanism, components of the nuclear transport apparatus have been implicated in genetic conflicts in Drosophila, especially in the male germ line. The best understood case is represented by a truncated RanGAP gene duplication that is part of the segregation distorter system in Drosophila melanogaster. Consistent with the hypothesis that the nuclear transport pathway is at the heart of mediating genetic conflicts, both nucleoporins and directionality imposing components of nuclear transport have previously been shown to evolve under positive selection. Here, we present a comprehensive phylogenomic analysis of importins (karyopherins) in Drosophila evolution. Importins are adaptor molecules that physically mediate the transport of cargo molecules and comprise the third component of the nuclear transport apparatus. We find that importins have been repeatedly gained and lost throughout various stages of Drosophila evolution, including two intriguing examples of an apparently coincident loss and gain of nonorthologous and noncanonical importin-α. Although there are a few signatures of episodic positive selection, genetic innovation in importin evolution is more evident in patterns of recurrent gene birth and loss specifically for function in Drosophila testes, which is consistent with their role in supporting host genomes defense against segregation distortion.
CHARACTERISTICS AND LONG-TERM OUTCOMES OF ELDERLY PATIENTS WITH ACUTE MYOCARDIAL INFARCTION COMPLICATED BY CARDIOGENIC SHOCK UNDERGOING PERCUTANEOUS CORONARY INTERVENTIONS.
Authors: Francesco Tomassini, Andrea Gagnor, Emanuele Tizzani, Maria Cristina Marocco, Vincenzo Infantino, Maria Rosa Conte, Ferdinando Varbella
Journal: Journal of the American College of Cardiology (2010)
The Neurobiology of Intervention and Prevention in Early Adversity
Authors: Philip A. Fisher, Kate G. Beauchamp, Leslie E. Roos, Laura K. Noll, Jessica Flannery, Brianna C. Delker
Journal: Annual Review of Clinical Psychology (2015)

Early adverse experiences are well understood to affect development and well-being, placing individuals at risk for negative physical and mental health outcomes. A growing literature documents the effects of adversity on developing neurobiological systems. Fewer studies have examined stress neurobiology to understand how to mitigate the effects of early adversity. This review summarizes the research on three neurobiological systems relevant to interventions for populations experiencing high levels of early adversity: the hypothalamic-adrenal-pituitary axis, the prefrontal cortex regions involved in executive functioning, and the system involved in threat detection and response, particularly the amygdala. Also discussed is the emerging field of epigenetics and related interventions to mitigate early adversity. Further emphasized is the need for intervention research to integrate knowledge about the neurobiological effects of prenatal stressors (e.g., drug use, alcohol exposure) and early adversity. The review concludes with a discussion of the implications of this research topic for clinical psychology practice and public policy.
α-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism
Authors: Natsuko Tokonami, Luciana Morla, Gabriel Centeno, David Mordasini, Suresh Krishna Ramakrishnan, Svetlana Nikolaeva, Carsten A. Wagner, Olivier Bonny, Pascal Houillier, Alain Doucet, Dmitri Firsov
Journal: Journal of Clinical Investigation (2013)

Paracrine communication between different parts of the renal tubule is increasingly recognized as an important determinant of renal function. Previous studies have shown that changes in dietary acid-base load can reverse the direction of apical α-ketoglutarate (αKG) transport in the proximal tubule and Henle's loop from reabsorption (acid load) to secretion (base load). Here we show that the resulting changes in the luminal concentrations of αKG are sensed by the αKG receptor OXGR1 expressed in the type B and non-A-non-B intercalated cells of the connecting tubule (CNT) and the cortical collecting duct (CCD). The addition of 1 mM αKG to the tubular lumen strongly stimulated Cl(-)-dependent HCO(3)(-) secretion and electroneutral transepithelial NaCl reabsorption in microperfused CCDs of wild-type mice but not Oxgr1(-/-) mice. Analysis of alkali-loaded mice revealed a significantly reduced ability of Oxgr1(-/-) mice to maintain acid-base balance. Collectively, these results demonstrate that OXGR1 is involved in the adaptive regulation of HCO(3)(-) secretion and NaCl reabsorption in the CNT/CCD under acid-base stress and establish αKG as a paracrine mediator involved in the functional coordination of the proximal and the distal parts of the renal tubule.