tbuckley/cabot-search huggingface dataset:
Monocyte/macrophage androgen receptor suppresses cutaneous wound healing in mice by enhancing local TNF-α expression
Authors: Jiann-Jyh Lai, Kuo-Pao Lai, Kuang-Hsiang Chuang, Philip Chang, I-Chen Yu, Wen-Jye Lin, Chawnshang Chang
Journal: Journal of Clinical Investigation (2009)

Cutaneous wounds heal more slowly in elderly males than in elderly females, suggesting a role for sex hormones in the healing process. Indeed, androgen/androgen receptor (AR) signaling has been shown to inhibit cutaneous wound healing. AR is expressed in several cell types in healing skin, including keratinocytes, dermal fibroblasts, and infiltrating macrophages, but the exact role of androgen/AR signaling in these different cell types remains unclear. To address this question, we generated and studied cutaneous wound healing in cell-specific AR knockout (ARKO) mice. General and myeloid-specific ARKO mice exhibited accelerated wound healing compared with WT mice, whereas keratinocyte- and fibroblast-specific ARKO mice did not. Importantly, the rate of wound healing in the general ARKO mice was dependent on AR and not serum androgen levels. Interestingly, although dispensable for wound closure, keratinocyte AR promoted re-epithelialization, while fibroblast AR suppressed it. Further analysis indicated that AR suppressed wound healing by enhancing the inflammatory response through a localized increase in TNF-alpha expression. Furthermore, AR enhanced local TNF-alpha expression via multiple mechanisms, including increasing the inflammatory monocyte population, enhancing monocyte chemotaxis by upregulating CCR2 expression, and enhancing TNF-alpha expression in macrophages. Finally, targeting AR by topical application of a compound (ASC-J9) that degrades AR protein resulted in accelerated healing, suggesting a potential new therapeutic approach that may lead to better treatment of wound healing.
Benzodiazepine Use Among Depressed Patients Treated in Mental Health Settings
Authors: Marcia Valenstein, Kiran Khanujua Taylor, Karen Austin, Helen C. Kales, John F. McCarthy, Frederic C. Blow
Journal: American Journal of Psychiatry (2004)

Most depression treatment guidelines emphasize treatment with antidepressant medication and recommend that benzodiazepine use be minimized, particularly among elderly patients. However, little is known about patterns of benzodiazepine use in specialty mental health settings. The authors examined benzodiazepine use among a large sample of depressed patients treated in U.S. Department of Veterans Affairs (VA) mental health settings.The VA National Registry for Depression was used to identify patients treated for depression in specialty mental health settings in 129 VA facilities during the first 3 months of fiscal year 2001 (October 1 to December 31, 2000) (N=128,029). The VA pharmacy database was used to identify outpatients who filled a prescription for benzodiazepines. The authors report on the prevalence and patterns of outpatient benzodiazepine use during the study year (fiscal year 2001) and evaluate patient demographic and clinical factors associated with use.During the study year, 36% of the depressed patients filled a benzodiazepine prescription and 89% filled an antidepressant prescription. Most users (78%) received > or = 90 days' supply of benzodiazepines, and 61% received > or = 180 days' supply. Older patients, whites, Hispanics, and patients with comorbid anxiety disorders were more likely to use benzodiazepines. Older patients were also more likely to receive > or = 90 days' supply of benzodiazepines, compared with younger patients, but were treated with lower doses. Benzodiazepine use varied significantly with region of the country and facility.Depressed patients treated in mental health settings commonly receive long-term treatment with benzodiazepines in combination with antidepressants, a pattern of use that is inconsistent with guideline recommendations. Elderly patients are particularly likely to receive benzodiazepines. Further research on the effectiveness of this widespread practice is needed.
Narrowed TCR repertoire and viral escape as a consequence of heterologous immunity
Authors: M. Cornberg
Journal: Journal of Clinical Investigation (2006)

Why some virus-specific CD8 TCR repertoires are diverse and others restricted or "oligoclonal" has been unknown. We show here that oligoclonality and extreme clonal dominance can be a consequence of T cell cross-reactivity. Lymphocytic choriomeningitis virus (LCMV) and Pichinde virus (PV) encode NP205–212 epitopes that induce different but highly cross-reactive diverse TCR repertoires. Homologous viral challenge of immune mice only slightly skewed the repertoire and enriched for predictable TCR motifs. However, heterologous viral challenge resulted in a narrow oligoclonal repertoire with dominant clones with unpredictable TCR sequences. This shift in clonal dominance varied with the private, i.e., unique, specificity of the host's TCR repertoire and was simulated using affinity-based computer models. The skewing differences in TCR repertoire following homologous versus heterologous challenge were observed within the same private immune system in mice adoptively reconstituted with memory CD8 T cell pools from the same donor. Conditions driving oligoclonality resulted in an LCMV epitope escape variant in vivo resembling the natural Lassa virus sequence. Thus, T cell oligoclonality, including extremes in clonal dominance, may be a consequence of heterologous immunity and lead to viral escape. This has implications for the design of peptide-based vaccines, which might unintentionally prime for skewed TCR responses to cross-reactive epitopes.
Age-Related Changes of the Cervix Influence Human Papillomavirus Type Distribution
Authors: Philip E. Castle, Jose Jeronimo, Mark Schiffman, Rolando Herrero, Ana C. Rodríguez, M. Concepción Bratti, Allan Hildesheim, Sholom Wacholder, L. Rodney Long, Leif Neve, Ruth Pfeiffer, Robert D. Burk
Journal: Cancer Research (2006)

Abstract Approximately 15 human papillomavirus (HPV) types cause virtually all cervical cancer whereas other HPV types are unrelated to cancer. We were interested in whether some noncarcinogenic types differ from carcinogenic in their affinity for the cervical transformation zone, where nearly all HPV-induced cancers occur. To examine this possibility, we tested cervical specimens from 8,374 women without cervical precancer and cancer participating in a population-based study in Guanacaste for &amp;gt;40 HPV types using PCR. We compared age-group specific prevalences of HPV types of the α9 species, which are mainly carcinogenic and include HPV16, to the genetically distinct types of the α3/α15 species (e.g., HPV71), which are noncarcinogenic and common in vaginal specimens from hysterectomized women. We related HPV detection of each group to the location of the junction between the squamous epithelium of the ectocervix and vagina and the columnar epithelium of the endocervical canal. Models evaluated the independent effects of amount of exposed columnar epithelium (ectopy) and age on the presence of α9 or α3/α15 types. Prevalence of α9 types (7.6%) peaked in the youngest women, declined in middle-aged women, and then increased slightly in older women. By contrast, prevalence of α3/α15 types (7.6%) tended to remain invariant or to increase with increasing age. Detection of α9 infections increased (Ptrend &amp;lt; 0.0005) but α3/α15 infections decreased (Ptrend &amp;lt; 0.0005) with increasing exposure of the columnar epithelia. Older age and decreasing cervical ectopy were independently positively associated with having an α3/α15 infection compared with having an α9 infection. These patterns need to be confirmed in other studies and populations. We suggest that these genetically distinct groups of HPV types may differ in tissue preferences, which may contribute to their differences in carcinogenic potential. (Cancer Res 2006; 66(2): 1218-24)
Lymphotoxin regulates commensal responses to enable diet-induced obesity
Authors: Vaibhav Upadhyay, Valeriy Poroyko, Tae-jin Kim, Suzanne Devkota, Sherry Fu, Donald Liu, Alexei V Tumanov, Ekaterina P Koroleva, Liufu Deng, Cathryn Nagler, Eugene B Chang, Hong Tang, Yang-Xin Fu
Journal: Nature Immunology (2012)
Accelerated exon evolution within primate segmental duplications
Authors: Belen Lorente-Galdos, Jonathan Bleyhl, Gabriel Santpere, Laura Vives, Oscar Ramírez, Jessica Hernandez, Roger Anglada, Gregory M Cooper, Arcadi Navarro, Evan E Eichler, Tomas Marques-Bonet
Journal: Genome biology (2013)

The identification of signatures of natural selection has long been used as an approach to understanding the unique features of any given species. Genes within segmental duplications are overlooked in most studies of selection due to the limitations of draft nonhuman genome assemblies and to the methodological reliance on accurate gene trees, which are difficult to obtain for duplicated genes. In this work, we detected exons with an accumulation of high-quality nucleotide differences between the human assembly and shotgun sequencing reads from single human and macaque individuals. Comparing the observed rates of nucleotide differences between coding exons and their flanking intronic sequences with a likelihood-ratio test, we identified 74 exons with evidence for rapid coding sequence evolution during the evolution of humans and Old World monkeys. Fifty-five percent of rapidly evolving exons were either partially or totally duplicated, which is a significant enrichment of the 6% rate observed across all human coding exons. Our results provide a more comprehensive view of the action of selection upon segmental duplications, which are the most complex regions of our genomes. In light of these findings, we suggest that segmental duplications could be subjected to rapid evolution more frequently than previously thought.
Oral Microbiology: Past, Present and Future
Authors: Xue‐song He, Wen‐yuan Shi
Journal: International Journal of Oral Science (2009)

Since the initial observations of oral bacteria within dental plaque by van Leeuwenhoek using his primitive microscopes in 1680, an event that is generally recognized as the advent of oral microbiological investigation, oral microbiology has gone through phases of "reductionism" and "holism". From the small beginnings of the Miller and Black period, in which microbiologists followed Koch's postulates, took the reductionist approach to try to study the complex oral microbial community by analyzing individual species; to the modern era when oral researchers embrace "holism" or "system thinking", adopt new concepts such as interspecies interaction, microbial community, biofilms, poly‐microbial diseases, oral microbiological knowledge has burgeoned and our ability to identify the resident organisms in dental plaque and decipher the interactions between key components has rapidly increased, such knowledge has greatly changed our view of the oral microbial flora, provided invaluable insight into the etiology of dental and periodontal diseases, opened the door to new approaches and techniques for developing new therapeutic and preventive tools for combating oral poly‐microbial diseases.
Hyperventilation, central autonomic control, and colonic tone in humans.
Authors: M J Ford, M J Camilleri, R B Hanson, J A Wiste, M J Joyner
Journal: Gut (1995)

Symptoms attributable to hyperventilation are common among patients with the irritable bowel syndrome (IBS); indeed, some have suggested that hyperventilation may exacerbate the alimentary symptoms of IBS. Hyperventilation changes haemodynamic function through central and peripheral mechanisms; its effects on colonic motor function, however, are unknown. The aim of this study, therefore, was to assess the effects of hyperventilation on colonic tone and motility and on cardiovascular autonomic activity, and to discover if hypocapnia was critical to elicit the response. Phasic and tonic motility of the transverse and sigmoid colon, end tidal PCO2, pulse rate, and beat to beat pulse variability were assessed before, during, and after a five minute period of hypocapnic hyperventilation in 15 healthy volunteers; in seven other subjects, effects of both eucapnic and hypocapnic hyperventilation were evaluated. Hypocapnic but not eucapnic hyperventilation produced an increase in colonic tone and phasic contractility in the transverse and sigmoid regions and an increase in pulse rate and pulse interval variability. The findings are consistent with inhibition of sympathetic innervation to the colon or direct effects of hypocapnia on colonic smooth muscle, or both. These physiological gut responses suggest that some of the changes in colonic function are caused by altered brain or autonomic control mechanisms.
G Protein–Coupled Estrogen Receptor Is Apoptotic and Correlates with Increased Distant Disease-Free Survival of Estrogen Receptor–Positive Breast Cancer Patients
Authors: Stefan Broselid, Benxu Cheng, Martin Sjöström, Kristina Lövgren, Heather L.P. Klug-De Santiago, Mattias Belting, Karin Jirström, Per Malmström, Björn Olde, Pär-Ola Bendahl, Linda Hartman, Mårten Fernö, L.M. Fredrik Leeb-Lundberg
Journal: Clinical Cancer Research (2013)

Abstract Purpose: G protein–coupled estrogen receptor 1 (GPER1), previously named GPR30, is a membrane receptor reported to mediate nongenomic estrogen responses. We investigated if GPER1 expression correlates with any clinicopathologic variables and distant disease-free survival (DDFS) in patients with breast cancer, if any prognostic impact of the receptor is dependent on estrogen receptor-α (ER-α) status, and if the receptor impacts apoptotic signaling in ER-positive breast cancer cells. Experimental Design: GPER1 expression was analyzed by immunohistochemistry in breast tumors from 273 pre- and postmenopausal stage II patients, all treated with adjuvant tamoxifen for 2 years (cohort I) and from 208 premenopausal lymph node-negative patients, of which 87% were not subjected to any adjuvant systemic treatment (cohort II). GPER1-dependent proapoptotic signaling was analyzed in MCF7 cells with and without GPER1 knockdown, T47D cells, HEK293 cells (HEK), and HEK stably expressing GPER1 (HEK-R). Results: GPER1 positively correlates with ER and progesterone receptor expression. Multivariate analysis showed that GPER1 is an independent prognostic marker of increased 10-year DDFS in the ER-positive subgroup. HEK-R has higher basal proapoptotic signaling compared with HEK including increased cytochrome C release, caspase-3 cleavage, PARP cleavage, and decreased cell viability. Treating HEK-R with the proteasome inhibitor epoxomicin, to decrease GPER1 degradation, further increases receptor-dependent proapoptotic signaling. Also, GPER1 knockdown decreases basal and agonist-stimulated proapoptotic receptor signaling in MCF7 cells. Conclusions: GPER1 is a prognostic indicator for increased DDFS in ER-positive breast cancer, which may be associated with constitutive GPER1-dependent proapoptotic signaling in ER-positive breast cancer cells. Clin Cancer Res; 19(7); 1681–92. ©2013 AACR.
Effects of α-Glucosidase Inhibition on Meal Glucose Tolerance and Timing of Insulin Administration in Patients With Type I Diabetes Mellitus
Authors: George Dimitriadis, Eryfilli Hatziagellaki, Evangelos Alexopoulos, Olga Kordonouri, Vasiliki Komesidou, Manolis Ganotakis, Sotirios Raptis
Journal: Diabetes Care (1991)

Objective Miglitol, an α-glucosidase inhibitor, delays absorption of carbohydrates. This study was undertaken to determine the potential of this agent as an adjunct to insulin in the treatment of diabetes. Research Design And Methods Twelve nonobese patients with insulin-dependent (type I) diabetes mellitus were randomly selected from the outpatient diabetes clinic. The patients were made euglycemic with the Biostator, and postprandial hyperglycemia was determined under the following conditions: protocol 1, subcutaneous injection of insulin (13 ± 1 U) given 60 min before the meal, with insulin dosages determined by the Biostator; protocols 2 and 3 same as protocol 1 but with insulin given at the time of meal ingestion; protocols 4 and 5 same as protocol 1 but with insulin given 30 min before the meal. Miglitol (100 mg) was administered in protocols 2 and 4 and placebo in protocols 3 and 5. Results When insulin was given 30 min before the meal with miglitol (protocol 4) or placebo (protocol 5), plasma glucose increased from 4.94 ± 0.16 to 5.94 ± 0.55 mM and from 5.11 ± 0.22 to 8.22 ± 0.72 mM, respectively (P &amp;lt; 0.01). When insulin was given at the time of the meal with miglitol (protocol 2) or placebo (protocol 3), plasma glucose increased from 5.44 ± 0.27 to 7.77 ± 0.5 mM and from 5.72 ± 0.22 to 10.83 ± 0.77 mM, respectively (P &amp;lt; 0.01). When insulin was given 60 min before the meal (protocol 1), plasma glucose initially decreased from 5.61 ± 0.38 to 4.33 ± 0.33 mM and then increased to 6.94 ± 0.66 mM after the meal.(ABSTRACT TRUNCATED AT 250 WORDS)
Initiation of the adaptive immune response to <i>Mycobacterium tuberculosis</i> depends on antigen production in the local lymph node, not the lungs
Authors: Andrea J. Wolf, Ludovic Desvignes, Beth Linas, Niaz Banaiee, Toshiki Tamura, Kiyoshi Takatsu, Joel D. Ernst
Journal: The Journal of Experimental Medicine (2007)

The onset of the adaptive immune response to Mycobacterium tuberculosis is delayed compared with that of other infections or immunization, and allows the bacterial population in the lungs to expand markedly during the preimmune phase of infection. We used adoptive transfer of M. tuberculosis Ag85B-specific CD4+ T cells to determine that the delayed adaptive response is caused by a delay in initial activation of CD4+ T cells, which occurs earliest in the local lung-draining mediastinal lymph node. We also found that initial activation of Ag85B-specific T cells depends on production of antigen by bacteria in the lymph node, despite the presence of 100-fold more bacteria in the lungs. Although dendritic cells have been found to transport M. tuberculosis from the lungs to the local lymph node, airway administration of LPS did not accelerate transport of bacteria to the lymph node and did not accelerate activation of Ag85B-specific T cells. These results indicate that delayed initial activation of CD4+ T cells in tuberculosis is caused by the presence of the bacteria in a compartment that cannot be mobilized from the lungs to the lymph node, where initial T cell activation occurs.
GIS and Health Care
Authors: Sara L. McLafferty
Journal: Annual Review of Public Health (2003)

▪ Abstract GIS and related spatial analysis methods provide a set of tools for describing and understanding the changing spatial organization of health care, for examining its relationship to health outcomes and access, and for exploring how the delivery of health care can be improved. This review discusses recent literature on GIS and health care. It considers the use of GIS in analyzing health care need, access, and utilization; in planning and evaluating service locations; and in spatial decision support for health care delivery. The adoption of GIS by health care researchers and policy-makers will depend on access to integrated spatial data on health services utilization and outcomes and data that cut across human service systems. We also need to understand better the spatial behaviors of health care providers and consumers in the rapidly changing health care landscape and how geographic information affects these dynamic relationships.
The Croonian Lectures on the Difference between the Sexes in Regard to the Aspect and Treatment of Disease
Authors: J. B. Hicks
Journal: BMJ (1877)

muscles in these' parts into action.When, for example, the skin of the poisoned leg was pinched, the irritation was transmitted up the sensory nerves, in the direction of the arrows, towards the' spinal cord, and reflected by it down the motor nerves of the other limb to the muscles both above and below the knee.But it was only below the knee, in the part protected from the poison, that they responded to the stimulus.As he had previously determined that the contractility of the muscles was not affected by the poison, this experiment seemed to prove that the action of the poison was limited to the peripheral ends of the motor nerves.For the sensory nerves, the spinal cord, and the trunks of the motor nerves abo-ve the knee had all been exposed to the action of the poison, and yet they still continued to do their work.Thus, it appears that the fault must lie with the terminations of the motor nerves within the muscles, and with them only.It often happens that the discovery of some prominent fact throws others into the shade for a while, and it is only after some time that its importance, at first overlooked, begins to be recognised.Thus it was
Infliximab: An effective rescue therapy in refractory extra-pulmonary sarcoidosis
Authors: Rezaur R. Abdullah, Athol U. Wells, Elizabeth A. Renzoni, Nilesh Morar, Toby M. Maher, Gregory J. Keir
Journal: European Respiratory Journal (2013)

Background 

Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. In cases of progressive organ threatening disease, corticosteroids form the mainstay of treatment. However, in the treatment of refractory sarcoidosis, infliximab, a monoclonal anti-TNF-α antibody, may provide a vital therapeutic alternative.

Objectives 

The Chelsea & Westminster Hospital Dermatology Department and Interstitial Lung Disease Unit at the Royal Brompton Hospital, London (U.K.), serve as national tertiary referral centres for refractory cutaneous and systemic sarcoidosis. We report a retrospective analysis of infliximab as a treatment for recalcitrant disease and explore its place in the treatment algorithm.

Results 

Between February 2009 and December 2012, thirteen patients received infliximab for progressive cutaneous, upper airway (ear, nose and throat; ENT), or pulmonary disease. In all patients, sarcoidosis had progressed despite the use of at least two systemic immunosuppressive agents. Following infliximab, six patients with skin lesions reported greater than 50% improvement, and three patients reported complete resolution. Four patients with ENT involvement (three of whom also had progressive skin involvement) experienced symptomatic and nasendoscopic improvements. In three patients with progressive pulmonary sarcoidosis, there was no significant change in symptoms, chest radiographs or pulmonary function tests. Six patients reported improvement in psychological distress following treatment.

Conclusion 

Infliximab appears to be a safe and highly effective ‘rescue’ therapy for cutaneous and upper airway sarcoidosis. Whether infliximab is of benefit in progressive pulmonary sarcoidosis is less clear.
Reduced lung function at birth may be a risk factor for later asthma
Authors: Raymond Ramnarine
Journal: Thorax (2007)

▴ Haland G, Lodrup Carlsen KC, Sandvik L, et al . Reduced lung function at birth and the risk of asthma at 10 years of age. N Engl J Med2006;355:1682–9.

[OpenUrl][1][CrossRef][2][PubMed][3]



A wheeze during childhood may be related to the development of asthma in later life, especially if it is a “transient early wheeze”. The authors have studied whether lung function abnormalities in a child shortly after birth could be used as a predictor of asthma at age 10.

The lung function of 802 newborns was measured (mean age 2.7; …

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