tbuckley/cabot-search huggingface dataset:
Granulocytopenia with marked lymphocytosis manifesting sjogren syndrome
Authors: James Goske, Ali D. Askari, Eliot Dickman, Walter B. Forman, Edward D. Crum
Journal: American Journal of Hematology (1980)

Abstract Sjogren syndrome is a multi‐system disease leading to diverse organ involvement during its course [1, 2]. Hematologic abnormalities described in Sjogren syndrome include anemia, mild leukopenia [3, 4], eosinophilia, elevated erythrocyte sedimentation rate, hypergammaglobulinemia, mixed cryoglobulinemia, and a variety of autoantibodies [5]. Marked lymphocytosis with granulocytopenia is distinctly unusual and has not been previously reported. We reporf a case of Sjogren syndrome who presented with constellation of the latter problems without prominent sicca manifestations.
Doctor Chekhov: a Study in Literature &amp; Medicine, by John Coope
Authors: J. T. Hart
Journal: BMJ (1997)

John Coope, Cross Publishing, £15, pp 159 ISBN 1 873295 21 9

If you are looking for a Christmas present for anyone you are really fond of, secretly including yourself, you won't find better than this. The major existing biographies of Chekhov available in English are stuffed with facts, but none takes his work as a doctor seriously—as Chekhov himself most certainly did. Even the short work by V S Pritchett somehow manages to be rather dull. As John Coope shows, however, even judged simply as an exceptionally conscientious “Zemstvo” doctor trying to cope with famine, cholera, and boneheaded administrations, and then, as …
Histological increase in inflammatory infiltrate in sun-exposed skin of female subjects: the possible involvement of matrix metalloproteinase-1 produced by inflammatory infiltrate on collagen degradation
Authors: T. Hase, K. Shinta, T. Murase, I. Tokimitsu, M. Hattori, R. Takimoto, R. Tsuboi, H. Ogawa
Journal: British Journal of Dermatology (2000)

To investigate morphological changes occurring during cutaneous photoageing, a correlation between the number of infiltrating cells in the dermis and the degree of collagen damage was examined using sections from clinically normal chronically sun-exposed and sun-protected skin of Japanese female subjects. Haematoxylin and eosin-stained sections from 134 sun-exposed (subjects aged 3-82 years) and 73 sun-protected (subjects aged 1-86 years) areas demonstrated a predominant lymphoid cell and to a lesser extent histiocyte infiltration. The mean +/- SD number of lymphoid cells and histiocytes in the sun-exposed skin sections (427.0+/-192.2 and 147.8+/-83.3 cells/mm2, respectively) was significantly higher than in the sun-protected skin sections (292.6+/-98.3 and 125.9+/-59.0 cells/mm2, respectively) (P < 0.001 and P < 0.05, respectively), and the number of lymphoid cells in the sun-exposed skin sections increased significantly with age up to 50 years (r = 0.400, P < 0.001). Sun-exposed skin sections with severe collagen degeneration had a significantly higher number of lymphoid cells than those with slightly degenerated collagen (mean 626.3 vs. 482.4 cells/mm2, P < 0.01). The mean count of mast cells in sun-exposed skin was 202.0 cells/mm2; this did not vary with the age of the subjects or the level of collagen damage. Immunohistochemical studies using 24 frozen sections identified most of the lymphoid cells infiltrating sun-exposed skin as memory T lymphocytes (CD3+, CD4+ and CD45RO+). The number of cells which displayed immunoreactivity to matrix metalloproteinase (MMP)-1 in the sun-exposed skin sections was significantly higher than in the sun-protected skin sections (mean 170.2 vs. 113.6 cells/mm2, P < 0.05). Among these cells were observed CD3 and MMP-1 double-stained T lymphocytes, and T lymphocytes contacting MMP-1-positive cells. These morphological observations suggest that T lymphocytes infiltrating photodamaged skin may play a part in the degeneration and reduction of collagen through MMP-1 activity.
Abstract 320: Ultrafast Cooling Induced by Total Liquid Ventilation Limits Early Oxidative Stress and Blood Brain Barrier Disruption After Cardiac Arrest
Authors: Matthias Kohlhauer, Isabelle Remy-Jouet, Fanny Lidouren, Jean-Damien Ricard, Raymond Robert, Mariana Barretto, Philippe Micheau, Hervé Walti, Pierre Carli, Benoit Vivien, Vincent Richard, Paul Mulder, Bijan Ghaleh, Alain Berdeaux, Renaud Tissier
Journal: Circulation (2014)

Introduction:  We previously demonstrated that total liquid ventilation (TLV) with perfluorocarbons can afford ultra-fast cooling and improve outcome after non-shockable cardiac arrest in rabbits.   Hypothesis:  We determined whether this protection could be linked to an early inhibition of reperfusion injury after cardiac arrest, including oxidative stress and blood brain barrier (BBB) disruption.   Methods:  Anesthetized rabbits were randomly submitted to 13 min of asphyxia followed by cardiopulmonary resuscitation. Then, they randomly underwent normothermic life support (Control group) or hypothermia induced by either i.v. cold saline (30 ml/kg; CONV group) or TLV (TLV group). In a first set of experiments, reactive oxygen species (ROS) were measured by electron paramagnetic resonance spectroscopy using CMH as spin probe on tissues sampled 30 min after cardiac arrest. In a second set of experiments, BBB integrity was assessed by the administration of Evans blue dye (EBD) 30 min after resuscitation. Brains were sampled 2 h later for morphological examination of EBD leakage.   Results:  In the TLV group, the target temperature of 32°C was reached within 5-15 min in the entire body. In comparison, 30 min after cardiac arrest, rectal temperature was only 36.1±0.4 °C and 38.2±0.2 °C in the CONV and Control group, respectively. ROS production was significantly decreased in the TLV group in the brain (cortex), heart and kidneys but not in the CONV group as compared to Control (n=8 in each group; Figure). This was accompanied by a significant decrease in EBD leakage extent in TLV as compared to Control and CONV (4.3±0.0%, 26.1±0.1% and 20.8±0.1% of brain volume, respectively; n=5 each).   Conclusion:  Ultra-fast cooling mitigates early events after cardiac arrest through limitation of ROS production and BBB disruption. This could explain the dramatic effect of ultra-fast cooling as compared to delayed hypothermia after resuscitation.
528. VEGF Gene Therapy with Retrogradely Transported Lentivirus Prolongs Survival in Mouse ALS Model
Authors: Mimoun Azzouz, Thanh Le, Scott G. Ralph, Fraser Wilkes, Arthur H. Burghes, Susan M. Kingsman, Kyriacous A. Mitrophanous, Nicholas D. Mazarakis
Journal: Molecular Therapy (2004)

We have developed a minimal lentiviral vector system that mediates efficient gene transfer into mammalian cells. The lentiviral vector system is derived from the non-primate equine infectious anaemia virus (EIAV, LentiVector®). LentiVector® has been shown to mediate long term gene transfer in the central nervous system with efficient expression and minimal toxicity (Mazarakis et al., 2001; Azzouz et al., 2002). We have previously demonstrated that pseudotyping of LentiVector® with the glycoprotein of the ERA strain of the rabies virus confers retrograde axonal transport on these vectors (Mazarakis et al., 2001). Delivery of such vectors by direct injection into muscle of rodent resulted in transduction of cells local to the site of injection. Efficient transduction of motor neurons (MNs) projecting into the injection site was also observed. These results, therefore indicated, that gene therapy approaches involving targeting of LentiVector® to MNs via peripheral administration into muscle may offer a promising strategy for gene therapy in motor neuron diseases (MND).
Art: Body Art: Marks of Identity
Authors: J. H. Tanne
Journal: BMJ (2000)

(see www.amnh.org/exhibitions/bodyart and www.discovery.com/exp/humancanvas/humancanvas.html)

Every time you shave, put on make up, or squeeze into tight jeans in an attempt to alter your appearance you are unwittingly following in the footsteps of your ancestors, who devised equally ingenious ways of doing the same thing. Now a history of our ancestors' methods of painting and piercing their bodies over the past 30 000 years is on display in a wondrous, imaginative, and sometimes frightening exhibition at the American Museum of Natural History. “There is no known culture in which people don't do this, whether permanently or temporarily,” said Ellen V Futter, president of the museum.

Why do people alter their bodies, sometimes painfully and permanently? Enid Schildkrout, curator of the show and chair of the museum's division of anthropology, thinks there are many reasons: “To be human. For beauty, as a sign of change or rebellion or conformity, to show status, to mark a moment, to be able to wear a certain ornament, to identify with spirits or ancestors or deities, to show group membership, to show gender distinctions.”

Organised in six major …
Prolonging the Delayed Phase of Myocardial Protection: Repetitive Adenosine A1Receptor Activation Maintains Rabbit Myocardium in a Preconditioned State 11Dr. Dana is supported by a Junior Research Fellowship, and Dr. Baxter by an Intermediate Fellowship, from the British Heart Foundation, London. Continuing support (Drs. Dana and Baxter) is provided by the Hatter Foundation, London.
Authors: Ali Dana, Gary F Baxter, J.Malcolm Walker, Derek M Yellon
Journal: Journal of the American College of Cardiology (1998)
Opposing roles of Dkk1 in LRP6 stabilization and Wnt signaling: implication for Wnt ligand-induced LRP6 down-regulation
Authors: Yonghe Li, Wenyan Lu, Guojun Bu
Journal: Cancer Research (2007)

4385   Classically, ligand-induced cell surface receptor down-regulation has been recognized as a longer-term mechanism for termination of a signaling pathway. The low density lipoprotein receptor-related protein-6 (LRP6) is an essential co-receptor for canonical Wnt signaling. Dickkopf 1 (Dkk1), a major secreted Wnt signaling antagonist, binds to LRP6 with high affinity and prevents the  Frizzled-Wnt-LRP5/6 complex formation in response to Wnts. Previous studies have demonstrated that Dkk1 promotes LRP6 internalization and degradation when it forms a ternary complex with the cell surface receptor, Kremen. Intriguingly, in the present study, we found that co-transfection of LRP6 and Dkk1 stabilizes LRP6 at the cell surface while still inhibiting Wnt/LRP6 signaling. This finding was recapitulated with exogenous Dkk1 application suggesting that Dkk1 acts on the cell surface and stabilizes LRP6 at non-functional state. We also found that Kremen coexpression abrogated the effect of Dkk1 on LRP6 expression, suggesting that the effect of Kremen2 is dominant over Dkk1 regulation of LRP6. Furthermore, we demonstrated a Wnt3A-induced LRP6 down-regulation; an effect blocked by Dkk1. Taken together, our results reveal a novel role for Dkk1 on Wnt ligand-induced LRP6 down-regulation and Wnt/LRP6 signaling.
Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects
Authors: Lampros A. Mavrogiannis, Ileana Antonopoulou, Alica Baxová, Stepán Kutílek, Chong A. Kim, Sofia M. Sugayama, Alberto Salamanca, Steven A. Wall, Gillian M. Morriss-Kay, Andrew O.M. Wilkie
Journal: Nature Genetics (2001)
Loss of Heterozygosity in Childhood Acute Lymphoblastic Leukemia Detected by Genome-Wide Microarray Single Nucleotide Polymorphism Analysis
Authors: Julie A.E. Irving, Lisa Bloodworth, Nick P. Bown, Marian C. Case, Linda A. Hogarth, Andrew G. Hall
Journal: Cancer Research (2005)

Abstract Loss of heterozygosity (LOH) is detectable in many forms of malignancy, including leukemia, using techniques such as microsatellite analysis and comparative genomic hybridization. However, these techniques are laborious and require the use of relatively large amounts of DNA if the whole genome is to be examined. Here we describe the use of oligonucleotide microarrays to characterize single nucleotide polymorphisms (SNPs) in lymphoblasts isolated from children with acute lymphoblastic leukemia for the pan-genomic mapping of LOH with a resolution of 100 to 200 kb. Results were compared with DNA obtained during remission and on relapse. Abnormalities were seen in 8 of 10 cases. The two cases with no abnormalities and one case that showed identical changes at relapse and presentation remain in remission 1 to 9 years following retreatment. The remaining seven patients died following relapse. In four cases, LOH was only detectable at relapse suggesting that progressive LOH may be a cause of disease progression and/or drug resistance. This was supported by detailed analysis of one case in which LOH involving the glucocorticoid receptor was associated with mutation of the remaining allele. The most frequent abnormality detected involved chromosome 9p. In each of the four cases where this was observed LOH included the INK4 locus. In three of the four cases, INK4 loss was only observed at relapse, suggesting that this abnormality may be commonly associated with treatment failure. These observations show that SNP array analysis is a powerful new tool for the analysis of allelic imbalance in leukemic blasts.
Abstract 1785: Distinct effect of aldehydes in anthracycline cytotoxicity in S. cerevisiae
Authors: Jana Sharrae Miles, Tryphon Mazu, Selina Darling-Reed, Hernan Flores-Rozas
Journal: Cancer Research (2014)

Abstract Anthracyclines are common chemotherapeutic agents used in many cancers which are refractory to other therapeutic alternatives. In triple negative breast cancer which is commonly observed in African-American women (AA) and tend to be more aggressive, carry worse prognoses and are harder to manage because they lack the molecular targets required for therapies, anthracyclines are some of the few therapeutic alternatives. Although effective, resistance to this agent usually arises and serious side-effects like the development of cardiomyopathy limits their use. To increase our knowledge of the pathways that protect cells from anthracyclines we carried out a genome-wide genetic screening in the eukaryotic model organism S. cerevisiae to identify gene defects that generate cells hypersensitive to doxorubicin. A total of 71 deletion strains displayed varying levels of sensitivity to anthracyclines. Among these, mutants of HOM6 confer significant increased sensitivity to doxorubicin. This effect appears to be due to the accumulation of the threonine intermediate L-aspartate-semialdehyde and can be abolished by the inactivation of a prior step, involving HOM3, which prevents the accumulation of the intermediate. In order to further characterize the synergism of aldehydes and doxorubicin, we have tested the effect of different aldehydes on the cytotoxicity of cells exposed to anthracyclines. Our data show that treatment with formaldehyde (2 mM) reduced the survival of the wild type strain to 78%. However, in the presence of doxorubicin, formaldehyde reduced the viability of the strain by between 31 to 39-fold (with 10 µM doxorubicin) relative to doxorubicin and formaldehyde alone and by ∼110-fold relative to doxorubicin at 150 µM concentration. Co-treatment with formaldehyde and doxorubicin of anthracycline-resistant strains siz1 and msh2 also shows increased toxicity. However, the synergistic effect is not as pronounced in these strains compared to the wild type. Among the aldehydes tested, formaldehyde was most effective. Glutaraldehyde and acetaldehyde displayed distinct effect on strains siz1, and ald5. The potential use of a combination of aldehydes and cytotoxic drugs could potentially lead to applications intended to enhance anthracycline-based therapy. This possibility will be discussed, as well as the targeting of aldehydes in relevant human pathways. Research supported by NIH/NCRR RCMI grant #RR03020 at Florida A&amp;M University. Citation Format: Jana Sharrae Miles, Tryphon Mazu, Selina Darling-Reed, Hernan Flores-Rozas. Distinct effect of aldehydes in anthracycline cytotoxicity in S. cerevisiae. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1785. doi:10.1158/1538-7445.AM2014-1785
Tackling Crizotinib Resistance: The Pathway from Drug Discovery to the Pediatric Clinic
Authors: Elizabeth R. Tucker, Laura S. Danielson, Paolo Innocenti, Louis Chesler
Journal: Cancer Research (2015)

Neuroblastoma is a childhood malignancy that has not yet benefitted from the rapid progress in the development of small-molecule therapeutics for cancer. An opportunity to take advantage of pharmaceutical innovation in this area arose when the identification of ALK fusion proteins in non-small cell lung cancer (NSCLC) occurred in parallel to the discovery of point mutations of ALK in neuroblastomas. ALK is now known to be a marker of poor outcome in neuroblastoma, and therefore, urgent development of specific ALK inhibitors to treat this devastating disease is a necessity. However, the translation of small molecules from adult directly into pediatric practice has thus far been challenging, due to mutation-specific structural variances in the ALK kinase domain. We discuss how the most recent structural and biological characterizations of ALK are directing preclinical and clinical studies of ALK inhibitors for both NSCLC and neuroblastoma.
B2-03: Supportive care and chemotherapy (CT) versus supportive care alone in advanced non-small cell lung cancer (NSCLC): A meta-analysis using individual patient data (IPD) from randomised controlled trials (RCTs)
Authors: Sarah Burdett, David Johnson, Lesley Stewart, Jayne Tierney, Cecile Le Pechoux
Journal: Journal of Thoracic Oncology (2007)
Multidrug-resistant tuberculosis in a kidney recipient
Authors: Ventsislava Pencheva, Daniela Petrova, Ognian Georgiev
Journal: European Respiratory Journal (2011)

A 38-year-old female, ten years after renal transplantation was referred to hospital with symptoms of fever and chest pain. The chest X-ray showed a massive solitary lession over the left hilus. The thoracic computed tomography detected infiltrative area in first, second and third segments in left lung with bilateral fibrosis and calcifications. The fiberoptic bronchoscopy showed a severe inflammation of the wall of upper left lobe, which was covered with white mucous material, easy bleeding on contact. The results of bronchoalveolar lavage were microbiological and histological negative for tuberculosis (TB) and other bacterial pathogens. The immunology test for TB (T-spot.TB) was positive. Due to the CT finding and positive T-SPOT.TB was started triple tuberculostatic therapy till the culture result for TB become ready. 34 days later the patient was re-hospitalized with fever and meningitis instead of the treatment. The result of the lumbal punction was lymphocyte liquid. The result from TB-culture was ready in the same time. Multidrug- resistant TB (MDR-TB) was proved in this patient. Antituberculosis treatment with four medicaments from second line was started.  Tuberculosis is a frequent infectious complication in patients on renal replacement therapy, as a result of immunosuppression from uremia and drugs in the post-transplantation period. The frequency of MDR-TB increases in last years. That requires treatment with second line drugs for longer period than patients infected with drug-sensitive strains and is with higher mortality rates.
Clinical Features of Alzheimer Disease With and Without Lewy Bodies
Authors: Eun Joo Chung, Ganesh M. Babulal, Sarah E. Monsell, Nigel J. Cairns, Catherine M. Roe, John C. Morris
Journal: JAMA Neurology (2015)

Lewy bodies are a frequent coexisting pathology in late-onset Alzheimer disease (AD). Previous studies have examined the contribution of Lewy bodies to the clinical phenotype of late-onset AD with variable findings.To determine whether the presence of Lewy body pathology influences the clinical phenotype and progression of symptoms in longitudinally assessed participants with AD.Retrospective clinical and pathological cohort study of 531 deceased participants who met the neuropathologic criteria for intermediate or high likelihood of AD according to the National Institute on Aging-Ronald Reagan Institute guidelines for the neuropathologic diagnosis of AD. All participants had a clinical assessment within 2 years of death. The data were obtained from 34 AD centers maintained by the National Alzheimer Coordinating Center and spanned from September 12, 2005, to April 30, 2013.Standardized neuropathologic assessment and then brain autopsy after death.Clinical and neuropsychiatric test scores.The mean (SD) age at death was statistically significantly younger for participants who had AD with Lewy bodies (77.9 [9.5] years) than for participants who had AD without Lewy bodies (80.2 [11.1] years) (P = .01). The mean (SD) age at onset of dementia symptoms was also younger for participants who had AD with Lewy bodies (70.0 [9.9] years) than for participants who had AD without Lewy bodies (72.2 [12.3] years) (P = .03). More men than women had AD with Lewy bodies (P = .01). The frequency of having at least 1 APOE ε4 allele was higher for participants who had AD with Lewy bodies than for participants who had AD without Lewy bodies (P = .03). After adjusting for age, sex, education, frequency of plaques (neuritic and diffuse), and tangle stage, we found that participants who had AD with Lewy bodies had a statistically significantly higher mean (SD) Neuropsychiatric Inventory Questionnaire score (6.59 [1.44] [95% CI, 3.75-9.42] vs 5.49 [1.39] [95% CI, 2.76-8.23]; P = .04) and a statistically significantly higher mean (SD) Unified Parkinson Disease Rating Scale motor score (0.81 [0.18] [95% CI, 0.45-1.17] vs 0.54 [0.18] [95% CI, 0.19-0.88]; P < .001) than did participants who had AD without Lewy bodies.Participants with both AD and Lewy body pathology have a clinical phenotype that may be distinguished from AD alone. The frequency of Lewy bodies in AD and the association of Lewy bodies with the APOE ε4 allele suggest potential common mechanisms for AD and Lewy body pathologies.