tbuckley/cabot-search huggingface dataset:
Postpartum onset of rheumatoid arthritis and other chronic arthritides: results from a patient register linked to a medical birth registry
Authors: M Wallenius, J F Skomsvoll, L M Irgens, K Å Salvesen, W Koldingsnes, K Mikkelsen, C Kaufmann, T K Kvien
Journal: Annals of the Rheumatic Diseases (2009)

Background: It is known that onset of rheumatoid arthritis (RA) is increased post partum. Objective: To compare incidence rates between RA and other chronic arthritides (OCA) 0–24 months after delivery, and to compare the incidence rates within each group 0–24 versus 25–48 months post partum. Methods: Premenopausal women from a Norwegian patient register were linked with the Medical Birth Registry of Norway to study the interval between delivery and time of diagnosis. Cox regression analysis with adjustments for age at delivery and birth order was applied to compare proportions of incident cases of RA and OCA with onset 0–24 months post partum. Poisson regression analysis with adjustment for the population at risk was applied to estimate the incidence rate ratio (IRR) 0–24 versus 25–48 months post partum. Results: Of 183 RA and 110 patients with OCA diagnosed after delivery, 69 (37.7%) had RA and 31 (28.2%) OCA during the first 24 months post partum (p = 0.09). The IRR (95% CI) for diagnosis during 0–24 months versus 25–48 months was 1.73 (1.11 to 2.70) (p = 0.01) for RA, 1.05 (0.59 to 1.84) (p = 0.86) for OCA. The IRR was 2.23 (1.06 to 4.70) and 1.87 (0.67 to 5.21), respectively, when only considering diagnoses after the first pregnancy. Clinical characteristics were similar within each diagnostic group. Conclusion: The proportions of incident cases with onset 0–24 months after delivery were not different between RA and OCA. A peak in incidence during 0–24 months was seen in the RA group, both when considering all pregnancies and only the first pregnancy.
The Transmembrane Sequence of Human Histocompatibility Leukocyte Antigen (HLA)-C as a Determinant in Inhibition of a Subset of Natural Killer Cells
Authors: Daniel M. Davis, Ofer Mandelboim, Isabel Luque, Eishi Baba, Jonathan Boyson, Jack L. Strominger
Journal: The Journal of Experimental Medicine (1999)

Molecular interactions with the extracellular domains of class I major histocompatibility complex proteins are major determinants of immune recognition that have been extensively studied both physically and biochemically. However, no immunological function has yet been placed on the transmembrane or cytoplasmic amino acid sequences of these proteins despite strict conservation of unique features within each class I major histocompatibility complex locus. Here we report that lysis by a subset of natural killer (NK) cells inhibited by target cell expression of human histocompatibility leukocyte antigen (HLA)-Cw6 or -Cw7 was not inhibited by expression of chimeric proteins consisting of the extracellular domains of HLA-C and the COOH-terminal portion of HLA-G. Assays using transfectants expressing a variety of HLA-Cw6 mutants identified the transmembrane sequence and, in particular, cysteine at position 309 as necessary for inhibition of 68% (25/37) of NK cell lines and 23% (33/145) of NK clones tested. Moreover, these NK clones inhibited by target cell expression of HLA-Cw6 and dependent upon the transmembrane sequence were found not to express or to only dimly express NK inhibitory receptors (NKIR1) that are EB6/HP3E4-positive. Furthermore, assays using monoclonal antibody blocking suggest that an NK receptor other than NKIR1 or CD94 is responsible for recognition dependent upon the transmembrane sequence of HLA-Cw6.
Role of High-Affinity Receptors and Membrane Transporters in Nonsynaptic Communication and Drug Action in the Central Nervous System
Authors: E S Vizi
Journal: Pharmacological Reviews (2000)

Neurochemical and morphological evidence has shown that some neurotransmitters or substances may be released from both synaptic and nonsynaptic sites for diffusion to target cells more distant than those observed in regular synaptic transmission. There are functional interactions between neurons without synaptic contacts, and matches between release sites and localization of receptors sensitive to the chemical signal are exceptions rather than the rule in the central nervous system. This also indicates that besides cabled information signaling (through synapses), there is a "wireless" nonsynaptic interaction between axon terminals. This would be a form of communication transitional between discrete classical neurotransmission (in Sherrington's synapse) and the relatively nonspecific neuroendocrine secretion. Recent findings indicate that in addition to monoamines (norepinephrine, dopamine, serotonin), other transmitters, such as acetylcholine and nitric oxide (NO), may also be involved in these nonsynaptic interactions. It has been shown that NO, an ideal mediator of nonsynaptic communication, can influence the function of uptake carrier systems, which may be an important factor in the regulation of extracellular concentration of different transmitters. This review will focus on the role of nonsynaptic receptors and transporters in presynaptic modulation of chemical transmission in the central nervous system. The nonsynaptic interaction between neurons mediated via receptors and transports of high affinity not localized in synapses has the potential to be an important contributor to the properties and function of neuronal networks. In addition, it will be suggested for the first time that the receptors and transporters expressed nonsynaptically and being of high affinity are the target of drugs taken by the patient.
Categorical and Dimensional Models of Personality Disorder
Authors: Timothy J. Trull, Christine A. Durrett
Journal: Annual Review of Clinical Psychology (2004)

We review major categorical and dimensional models of personality pathology, highlighting advantages and disadvantages of these approaches. Several analytic and methodological approaches to the question of the categorical versus dimensional status of constructs are discussed, including taxometric analyses, latent class analyses, and multivariate genetic analyses. Based on our review, we advocate a dimensional approach to classifying personality pathology. There is converging evidence that four major domains of personality are relevant to personality pathology: neuroticism/negative affectivity/emotional dysregulation; extraversion/positive emotionality; dissocial/antagonistic behavior; and constraint/compulsivity/conscientiousness. Finally, we discuss how dimensional approaches might be integrated into the diagnostic system, as well as some of the major issues that must be addressed in order for dimensional approaches to gain wide acceptance.
Mammary Tumorigenesis in Chemical Carcinogen-Treated Mice. IV. Induction of Mammary Ductal Hyperplasias2
Authors: Daniel Medina, M. R. Warner
Journal: JNCI Journal of the National Cancer Institute (1976)

BALB/cCrgl, C57BL/KI, and (C57BL/Ki × DBAf)F1 mice were treated with 7,12-dimethylbenz[a]anthracene (DMBA) or urethan to determine conditions that would induce a high frequency of ductal hyperplaslas in the mammary gland. Among virgin BALB/c mice treated with either 3.0 or 4.0 mg DMBA, ductal hyperplasias and mammary tumors were present in 50% and 31% of the mice, respectively. These ductal hyperplasias were characterized by intraluminal epithelial hyperplasia and capped by endbud-like structures that appeared abnormal. Hyperplastic alveolar nodules were not seen. Most mammary tumors were adenocarcinomas rather than the adenoacanthomas observed in DMBA-treated, pituitary isograft-bearing BALB/c mice. The predominant mammary lesions in urethan-treated, pituitary isograftbearing C57BL and (C57BL × DBAf)F1 mice were terminal duct (lobular) hyperplaslas characterized by intraluminal epithelial hyperplasia; the urethan-induced mammary tumors were a mixture of adenocarcinomas (36%), adenoacanthomas (5%), and fibroadenomas (59%). The induction by chemical carcinogens of intraductal hyperplaslas in a relatively high incidence, with associated mammary neoplasms, provides a system for study of the process of tumor progression in lesions similar to suspected high-risk lesions occurring in human breast cancer.
Administration of Marijuana to Heavy and Casual Marijuana Users
Authors: ROGER E. MEYER, RICHARD C. PILLARD, LEO M. SHAPIRO, STEVEN M. MIRIN
Journal: American Journal of Psychiatry (1971)

The authors compared six heavy and six casual smokers of marijuana, using placebo, a fixed dose of marijuana, and a self-selected ad lib dose. The subjects showed a modest decrease in perception and psychomotor task performance with both types of marijuana dose, though casual smokers showed a greater degree of impairment than did heavy smokers. Subjectively, casual smokers experienced perceptual and affective responses to a placebo condition that mimicked their experience under marijuana. Some heavy smokers showed evidence suggestive of a mild hallucinogenic effect. The authors urge that all studies using smoked marijuana take note of the subjects' previous smoking experience and that these data be considered in the interpretation of findings on the effects of cannabis.
Modification of PI3K- and MAPK-Dependent Chemotaxis in Aortic Vascular Smooth Muscle Cells by Protein Kinase C <sub>βII</sub>
Authors: Malcolm Campbell, Elisabeth R. Trimble
Journal: Circulation Research (2005)

Hyperglycemia increases expression of platelet-derived growth factor (PDGF)-beta receptor and potentiates chemotaxis to PDGF-BB in human aortic vascular smooth muscle cells (VSMCs) via PI3K and ERK/MAPK signaling pathways. The purpose of this study was to determine whether increased activation of protein kinase C (PKC) isoforms had a modulatory effect on the PI3K and ERK/MAPK pathways, control of cell adhesiveness, and movement. All known PKC isoforms were assessed but only PKCalpha and PKCbetaII levels were increased in 25 mmol/L glucose. However, only PKCbetaII inhibition affected (decreased) PI3K pathway and MAPK pathway activities and inhibited PDGF-beta receptor upregulation in raised glucose, and specific MAPK inhibition was required to completely block the effect of glucose. In raised glucose conditions, activity of the ERK/MAPK pathway, PI3K pathway, and PKCbetaII were all sensitive to aldose reductase inhibition. Chemotaxis to PDGF-BB (360 pmol/L), absent in 5 mmol/L glucose, was present in raised glucose and could be blocked by PKCbetaII inhibition. Formation of lamellipodia was dependent on PI3K activation and filopodia on MAPK activation; both lamellipodia and filopodia were eliminated when PKCbetaII was inhibited. FAK phosphorylation and cell adhesion were reduced by PI3K inhibition, and although MAPK inhibition prevented chemotaxis, it did not affect FAK phosphorylation or cell adhesiveness. In conclusion, chemotaxis to PDGF-BB in 25 mmol/L glucose is PKCbetaII-dependent and requires activation of both the PI3K and MAPK pathways. Changes in cell adhesion and migration speed are mediated mainly through the PI3K pathway.
Airway smooth muscle cell culture: application to studies of airway wall remodelling and phenotype plasticity in asthma
Authors: SJ Hirst
Journal: European Respiratory Journal (1996)

Chronic persistent asthma is characterized by poorly reversible airway obstruction. Histopathological studies of airways removed postmortem from patients with severe asthma reveal marked inflammatory and architectural changes associated with airway wall thickening. Increased airway smooth muscle content, occurring as a result of hyperplastic and/or hypertrophic growth, is believed to be one of the principal contributors to airway wall thickening. Intense interest is building to discover the mechanisms responsible for these long-term structural changes. In vitro cell culture offers a powerful and exacting approach to cellular and molecular studies of the long-term regulation of airway smooth muscle function. This review discusses the methodologies for establishing and maintaining cell cultures of airway smooth muscle. It also describes the characteristics of these cells in culture and addresses the potential importance of phenotype plasticity and its possible relationship to altered smooth muscle function in vivo. Drawing on parallels from vascular studies, this review focuses, in particular, on the synthetic nature of the airway smooth muscle cell, emphasizing its potential to alter the composition of the extracellular matrix environment and orchestrate key events in the process of chronic airway remodelling.
Parallel Evolution of Opsin Gene Expression in African Cichlid Fishes
Authors: K. E. O'Quin, C. M. Hofmann, H. A. Hofmann, K. L. Carleton
Journal: Molecular Biology and Evolution (2010)

Phenotypic evolution may occur either through alterations to the structure of protein-coding genes or their expression. Evidence for which of these two mechanisms more commonly contribute to the evolution of a phenotype can be garnered from examples of parallel and convergent evolution. The visual system of East African cichlid fishes is an excellent system with which to address this question. Cichlid fishes from Lakes Malawi (LM) and Victoria together exhibit three diverse palettes of coexpressed opsins and several important protein-coding mutations that both shift spectral sensitivity. Here we assess both opsin expression and protein-coding diversity among cichlids from a third rift lake, Lake Tanganyika (LT). We found that Tanganyikan cichlids exhibit three palettes of coexpressed opsins that largely overlap the short-, middle-, and long-wavelength–sensitive palettes of LM cichlids. Bayesian phenotypic clustering and ancestral state reconstructions both support the parallel evolution of the short- and middle-wavelength palettes among cichlids from LT and LM. In each case, these transitions occurred from different ancestors that expressed the same long-wavelength palette. We also identified similar but distinct patterns of correlated evolution between opsin expression, diet, and lens transmittance among cichlids from LT and LM as well. In contrast to regulatory changes, we identified few functional or potentially functional mutations in the protein-coding sequences of three variable opsins, with the possible exception of the SWS1 (ultraviolet) opsin. These results underscore the important contribution that gene regulation can make to rapid phenotypic evolution and adaptation.
Response to Letter Regarding Article, “Extravirgin Olive Oil Consumption Reduces Risk of Atrial Fibrillation: The PREDIMED (Prevención con Dieta Mediterránea) Trial”
Authors: Miguel Á. Martínez-González, Estefanía Toledo, Fernando Arós, Miquel Fiol, Dolores Corella, Jordi Salas-Salvadó, Emilio Ros, Maria I. Covas, Joaquín Fernández-Crehuet, José Lapetra, Miguel A. Muñoz, Monserrat Fitó, Luis Serra-Majem, Xavier Pintó, Rosa M. Lamuela-Raventós, Jose V. Sorlí, Nancy Babio, Pilar Buil-Cosiales, Valentina Ruiz-Gutierrez, Ramón Estruch, Alvaro Alonso
Journal: Circulation (2015)
Bactericidal versus Bacteriostatic Antibiotic Therapy of Experimental Pneumococcal Meningitis in Rabbits
Authors: W. Michael Scheld, Merle A. Sande
Journal: Journal of Clinical Investigation (1983)

A rabbit model of pneumococcal meningitis was used to examine the importance of bactericidal vs. bacteriostatic antimicrobial agents in the therapy of meningitis 112 animals were infected with one of two strains of type III Streptococcus pneumoniae. Both strains were exquisitely sensitive to ampicillin, minimum inhibitory concentration (MIC)/minimum bactericidal concentration (MBC)<0.125 μg/ml. The activity of chloramphenicol against the two strains varied: strain1—MIC 2 μg/ml, MBC 16 μg/ml; strain2—MIC 1 μg/ml, MBC 2 μg/ml. Animals were treated with either ampicillin or chloramphenicol in dosages that achieved a peak bactericidal effect in cerebrospinal fluid (CSF) for ampicillin against both strains. Two different dosages were used for chloramphenicol. The first dosage achieved a peak CSF concentration of 4.4±1.1 μg/ml that produced a bacteriostatic effect against strain1 and bactericidal effect against strain2. The second dosage achieved a bactericidal effect against both strains (mean peak CSF concentration 30.0 μg/ml). All animals were treated intramuscularly three times a day for 5 d. CSF was sampled daily and 3 d after discontinuation of therapy for quantitative bacterial cultures. Results demonstrate that only antimicrobial therapy that achieved a bactericidal effect in CSF was associated with cure. Over 90% of animals treated with one of the bactericidal regimens (i.e., animals in which the bacterial counts in CSF dropped >5 log10 colony-forming units [cfu]/ ml after 48 h) had sterile CSF after 5 d of treatment. On the other hand, the regimen that achieved bacteriostatic concentrations (CSF drug concentrations between the MIC and MBC) produced a drop of 2.4 log10 cfu/ml by 48 h; however, none of the animals that survived had sterile CSF after 5 d. These studies clearly demonstrate in a strictly controlled manner that maximally effective antimicrobial therapy of experimental pneumococcal meningitis depends on achieving a bactericidal effect in CSF.
“TRIMing” the Patient Population to Increase the Benefit of mTOR Inhibition
Authors: H. Ian Robins, Mark E. Burkard, Richard B. Halberg
Journal: JNCI Journal of the National Cancer Institute (2014)

inhibitor. This approval was based on a 6.9-month improvement in progression-free survival and a trend to overall survival benefit at the interim analysis (hazard ratio [HR] = 0.77; 95% CI = 0.57 to 1.04) (7). Similar results were observed from a randomized phase II trial in metastatic breast cancer. The combination of everolimus and tamoxifen improved response rate, progression-free survival, and overall survival, as compared with tamoxifen alone. The question of overcoming resistance relative to the HER2 locus was more recently addressed in the phase III BOLERO-3 trial (NCT01007942), which compared trastuzumab plus vinorelbine with or without everolimus in metastatic breast cancer patients
Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces
Authors: Italia A Asteriti, Maria Giubettini, Patrizia Lavia, Giulia Guarguaglini
Journal: Molecular Cancer (2011)

Abstract Background Aurora-A is an oncogenic kinase playing well-documented roles in mitotic spindle organisation. We previously found that Aurora-A inactivation yields the formation of spindles with fragmented poles that can drive chromosome mis-segregation. Here we have addressed the mechanism through which Aurora-A activity regulates the structure and cohesion of spindle poles. Results We inactivated Aurora-A in human U2OS osteosarcoma cells either by RNA-interference-mediated silencing or treating cultures with the specific inhibitor MLN8237. We show that mitotic spindle pole fragmentation induced by Aurora-A inactivation is associated with microtubule hyperstabilisation. Silencing of the microtubule-stabilising factor ch-TOG prevents spindle pole fragmentation caused by inactivation of Aurora-A alone and concomitantly reduces the hyperstabilisation of microtubules. Furthermore, decreasing pole-directed spindle forces by inhibition of the Eg5 kinesin, or by destabilisation of microtubule-kinetochore attachments, also prevents pole fragmentation in Aurora-A-inactivated mitoses. Conclusions Our findings indicate that microtubule-generated forces are imbalanced in Aurora-A-defective cells and exert abnormal pressure at the level of spindle poles, ultimately causing their fragmentation. This study therefore highlights a novel role of the Aurora-A kinase in regulating the balance between microtubule forces during bipolar spindle assembly.
Hygiene, Sanitation, and Water: What Needs to Be Done?
Authors: Sandy Cairncross, Jamie Bartram, Oliver Cumming, Clarissa Brocklehurst
Journal: PLoS Medicine (2010)

In the final article in a four-part PLoS Medicine series on water and sanitation, Sandy Cairncross and colleagues outline what needs to be done to make significant progress in providing more and better hygiene, sanitation, and water for all.
Anorexia Nervosa Associated with Acromegaloid Features, Onset of Acrocyanosis and Raynaud's Phenomenon and Worsening of Chilblains
Authors: M H A Rustin, J C Foreman, P M Dowd
Journal: Journal of the Royal Society of Medicine (1990)

Patients with anorexia nervosa may develop many physical and endocrinological complications. We wish to report two patients who developed soft tissue swelling of their hands and worsening of their peripheral vascular disease, evidenced by the appearance of acrocyanosis and Raynaud's phenomenon and more severe perniosis, following the onset of their anorexia nervosa.
General practitioners' access to x ray services
Authors: T S Brown
Journal: BMJ (1991)

11) mm Hg; (p<OOOl), and the median difference was 5 mm Hg (interquartile range 2-8 mm Hg; range 0-15 mm Hg).Muffling was recorded in 78% of the group and blood pressure was not heard to zero in any subject.These findings are similar to those of Perry et al,' though the distribution of differences between phase IV and phase V readings was shifted towards the right in our study (table ).Distribution (%) ofdifferences between diastolic pressures measured at phase I 'and at phase l in those with auidible muffling ofsounds Difference (mm Hg): 0-2 3-5 6-10 >10Brown and Adsett
Lack of Growth of a Pregnancy-Dependent Mouse Mammary Tumor (TPDMT-4) in the Absence of Pituitary Hormones2
Authors: Akio Matsuzawa, Tadashi Yamamoto
Journal: JNCI Journal of the National Cancer Institute (1977)

Mammary tumors of line TPDMT-4, established in DDD mice, were characterized by growth during pregnancy and regression after parturition; this resulted in higher growth peaks in subsequent pregnancies in breeders and no growth in virgins. The effect of hypophysectomy on tumor growth in mice given 17beta-estradiol (E) and progesterone (P) or deoxycorticosterone acetate (DCA) was investigated. Growth of cancers occurred in E+P- and E+DCA-treated virgins, but not in cholesterol-treated virgins. Tumors did not grow to palpable sizes in cholesterol-, E+P-, and E+DCA-treated hypophysectomized virgins; this indicated that pituitary hormones were essential for tumor growth. Impalpable cholesterol-treated, 5 of 10 E+P-treated, and 3 of 6 E+DCA-treated hypophysectomized animals. The neoplasms showed ductal and tubular structures that were lined by a single layer of well-differentiated buoidal epithelium, which suggested that the tumor line might be derived from ductal cells.
AN INFECTIOUS CUTANEOUS FIBROMA OF THE VIRGINIA WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS)
Authors: Richard E. Shope, Robert Mangold, Lester G. MacNamara, Keith R. Dumbell
Journal: The Journal of Experimental Medicine (1958)

A naturally occurring cutaneous fibroma of deer has proven to be experimentally transmissible in deer. The causative agent is a virus that is readily alterable through Berkefeld N candles and that survives in fibroma tissue for at least as long as 27 months in glycerol-saline at -20 degrees C. The experimentally produced deer fibroma has an incubation period of about 7 weeks, a very slow rate of growth, and a high regression rate.