tbuckley/cabot-search huggingface dataset:
Keratinocyte growth regulation by the products of immune cells.
Authors: G E Hancock, G Kaplan, Z A Cohn
Journal: The Journal of Experimental Medicine (1988)

We describe a bioassay that allows the in vitro investigation of the stimulatory and suppressive factors derived from immune cells in short-term cultures of human keratinocytes. In agreement with other assays, epidermal growth factor is not mitogenic for human keratinocytes. Supernatant fluid from human PBMC stimulated with Con A, from allo-MLRs, as well as supernatants from nonstimulated PBMC, possess growth-promoting molecules. Our results show that both activated and nonactivated T cells release growth factors. Suppressive molecules are produced preferentially by monocyte cultures. Two T cell products, IFN-gamma and transforming growth factor beta are both inhibitory for keratinocyte proliferation. Two other T cell products, IL-3 and GM-CSF, stimulate keratinocyte proliferation at nanogram concentrations. These results suggest the existence of regulatory circuits between the T cells of a dermal inflammatory infiltrate and the overlying epidermal keratinocytes. This may determine the fine control of epidermal proliferation and turnover leading either to enhanced wound repair or skin pathology.
Development and initial validation of the Brunel lifestyle physical activity questionnaire
Authors: C I Karageorghis, M M Vencato, N L D Chatzisarantis, A V Carron
Journal: British Journal of Sports Medicine (2005)

Objectives: To develop a valid and reliable internet based lifestyle physical activity questionnaire suitable for use among the United Kingdom population. Methods: After a detailed content analysis and item generation using a panel of experts, an internet based measure of lifestyle physical activity behaviour was developed. Data were collected from 1369 subjects in total. Confirmatory factor analysis was used to examine the two subscales of the Brunel lifestyle physical activity questionnaire among independent samples and by use of multisample analyses. Results: The confirmatory factor analysis showed the psychometric integrity of two subscales: planned physical activity and unplanned physical activity. Conclusion: The questionnaire is a valid and reliable instrument designed to provide an online behavioural assessment to be used in conjunction with a 12 week personalised fitness programme delivered through the internet.
Delineation, Functional Validation, and Bioinformatic Evaluation of Gene Expression in Thyroid Follicular Carcinomas with the <i>PAX8-PPARG</i> Translocation
Authors: Thomas J. Giordano, Amy Y.M. Au, Rork Kuick, Dafydd G. Thomas, Daniel R. Rhodes, Kenneth G. Wilhelm, Michelle Vinco, David E. Misek, Donita Sanders, Zhaowen Zhu, Raffaele Ciampi, Samir Hanash, Arul Chinnaiyan, Roderick J. Clifton-Bligh, Bruce G. Robinson, Yuri E. Nikiforov, Ronald J. Koenig
Journal: Clinical Cancer Research (2006)

Abstract A subset of follicular thyroid carcinomas contains a balanced translocation, t(2;3)(q13;p25), that results in fusion of the paired box gene 8 (PAX8) and peroxisome proliferator-activated receptor γ (PPARG) genes with concomitant expression of a PAX8-PPARγ fusion protein, PPFP. PPFP is thought to contribute to neoplasia through a mechanism in which it acts as a dominant-negative inhibitor of wild-type PPARγ. To better understand this type of follicular carcinoma, we generated global gene expression profiles using DNA microarrays of a cohort of follicular carcinomas along with other common thyroid tumors and used the data to derive a gene expression profile characteristic of PPFP-positive tumors. Transient transfection assays using promoters of four genes whose expression was highly associated with the translocation showed that each can be activated by PPFP. PPFP had unique transcriptional activities when compared with PAX8 or PPARγ, although it had the potential to function in ways qualitatively similar to PAX8 or PPARγ depending on the promoter and cellular environment. Bioinformatics analyses revealed that genes with increased expression in PPFP-positive follicular carcinomas include known PPAR target genes; genes involved in fatty acid, amino acid, and carbohydrate metabolism; micro-RNA target genes; and genes on chromosome 3p. These results have implications for the neoplastic mechanism of these follicular carcinomas.
A 20-year-old male with thoracic pain and a lower thoracic mass
Authors: W. K. de Jong, W. T. A. van der Graaf, E. J. van der Jagt, T. J. Klinkenberg, H. J. M. Groen, W. Timens, W. R. Douma
Journal: European Respiratory Journal (2005)

Patients do not usually vomit after operations, and no antiemetic drug can be used without some risk. Medical Letter consultants therefore believe that antiemetics should be used not as a routine, but only when nausea and vomiting are disturbing the comfort or treatment of the patient, especially when the results of surgery are threatened (for example, in the eye).
Intracellular pharmacokinetics of methotrexate polyglutamates in human breast cancer cells. Selective retention and less dissociable binding of 4-NH2-10-CH3-pteroylglutamate4 and 4-NH2-10-CH3-pteroylglutamate5 to dihydrofolate reductase.
Authors: J Jolivet, B A Chabner
Journal: Journal of Clinical Investigation (1983)

Methotrexate (MTX-Glu1) exerts its antitumor effects through its potent inhibition of dihydrofolate reductase (DHFR), the enzyme responsible for maintaining the cellular pool of reduced folates. Since the drug-enzyme complex (bound drug) is slowly dissociable, an excess of drug (unbound or free drug) above that required to bind all enzyme sites is required in order to compete with substrate for sites made available by enzyme-drug dissociation. We have examined the role of the polyglutamyl metabolites of MTX-Glu1 containing two to five glutamyl (MTX-Glu2-5) groups in gamma peptide linkage in maintaining an intracellular pool of free drug and in forming slowly dissociable complexes with DHFR. During 24-h incubations of ZR-75-B human breast cancer cells with 2 microM MTX-Glu1, we observed the progressive formation of derivatives with two to five glutamyl groups, which rapidly replaced the parent compound on enzyme binding sites and represented 85% of both unbound and bound intracellular drug at the end of incubation. When cells were then placed in drug-free medium, the rates of disappearance of drug and metabolites from the intracellular bound and free fractions decreased with increasing glutamyl chain length. Over 90% of both bound and free MTX-Glu1 left the cells within 1 h, greater than 90% of MTX-glu2 left within 6 h, and greater than 90% of MTX-Glu3 left the bound and free fractions within 24 h. In contrast, free MTX-Glu4 fell by only 63% and bound by only 23% after 24 h, while free MTX-Glu5 increased by 52% after 6 h in drug-free medium and bound MTX-Glu5 increased threefold after 24 h, as it replaced the other forms of drug bound to DHFR. These results suggested a rapid dissociation of MTX-GLu1 and -Glu2 from the enzyme, and a slower dissociation of the longer chain length derivatives. This conclusion was confirmed by examining the rates at which [3H]MTX-Glu1 through -Glu5 could be replaced on enzyme binding sites by a fivefold or greater excess of unlabeled MTX-Glu1. Bound [3H]MTX-Glu1 and -Glu2 had dissociation t 1/2 of 12 and 30 min, respectively, while -Glu3, -Glu4, and -Glu5 had t 1/2 of 102, 108, and 120 min. These experiments demonstrated that the longer chain polyglutamates have prolonged intracellular retention and can be dissociated less readily than MTX-Glu2 from DHFR, properties likely to make them more efficient DHFR inhibitors than the parent drug and of potential importance in extending the duration of drug action in tumor cells.
Excitatory Amino Acid Neurotransmission: NMDA Receptors and Hebb-Type Synaptic Plasticity
Authors: C W Cotman, D T Monaghan
Journal: Annual Review of Neuroscience (1988)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Functional results with aortic ball valve prostheses (Starr-Edwards) followed for two to three years.
Authors: V O Bjork, I Cullhed
Journal: Thorax (1967)

Summary: Historically, surgical management of cerebral aneurysms during pregnancy has been controversial. Debate originally focused on early versus late intervention, before or after delivery of the fetus. More recently, treatment has centered on rapid intervention. We describe the endovascular treatment of cerebral artery aneurysms with Guglielmi detachable coils in three pregnant women.
Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003–11): a national observational cohort study
Authors: Zhongwei Jia, Yurong Mao, Fujie Zhang, Yuhua Ruan, Ye Ma, Jian Li, Wei Guo, Enwu Liu, Zhihui Dou, Yan Zhao, Lu Wang, Qianqian Li, Peiyan Xie, Houlin Tang, Jing Han, Xia Jin, Juan Xu, Ran Xiong, Decai Zhao, Ping Li, Xia Wang, Liyan Wang, Qianqian Qing, Zhengwei Ding, Ray Y Chen, Zhongfu Liu, Yiming Shao
Journal: The Lancet (2012)
Transcription Start Site Evolution in Drosophila
Authors: Bradley J. Main, Andrew D. Smith, Hyosik Jang, Sergey V. Nuzhdin
Journal: Molecular Biology and Evolution (2013)

Transcription start site (TSS) evolution remains largely undescribed in Drosophila, likely due to limited annotations in non-melanogaster species. In this study, we introduce a concise new method that selectively sequences from the 5'-end of mRNA and used it to identify TSS in four Drosophila species, including Drosophila melanogaster, D. simulans, D. sechellia, and D. pseudoobscura. For verification, we compared our results in D. melanogaster with known annotations, published 5'-rapid amplification of cDNA ends data, and with RNAseq from the same mRNA pool. Then, we paired 2,849 D. melanogaster TSS with its closest equivalent TSS in each species (likely to be its true ortholog) using the available multiple sequence alignments. Most of the D. melanogaster TSSs were successfully paired with an ortholog in each species (83%, 86%, and 55% for D. simulans, D. sechellia, and D. pseudoobscura, respectively). On the basis of the number and distribution of reads mapped at each TSS, we also estimated promoter-specific expression (PSE) and TSS peak shape, respectively. Among paired TSS orthologs, the location and promoter activity were largely conserved. TSS location appears important as PSE, and TSS peak shape was more frequently divergent among TSS that had moved. Unpaired TSS were surprisingly common in D. pseudoobscura. An increased mutation rate upstream of TSS might explain this pattern. We found an enrichment of ribosomal protein genes among diverged TSS, suggesting that TSS evolution is not uniform across the genome.
Prevention of running-related injuries in novice runners: are we running on empty?
Authors: Evert Verhagen
Journal: British Journal of Sports Medicine (2012)

Running is one of the fastest-growing sports activities worldwide. In the Netherlands, with a population 17 million, about 1.4 million individuals engage in this activity regularly—either as part of a club or as an individual. Reasons for the contemporary public interest in running probably include a desire for weight reduction or a healthy lifestyle in general, combined with the low entry level, quick health effects and social elements. This is encouraging from a public health standpoint.

On the other hand, the most recent Dutch sports injury data reveal that 420 000 of our 3.5 million annual sports injuries are running related. This represents 5.1 injuries per 1000 h of running.1 Novice runners have a much greater risk of injury than do those who have been running for some time.2 Injuries work against the potential public health gain of running. Prevention of running injuries in novice runners will promote running consistency. In combination with the current running ‘hype’ and the positive health effects achieved through running, successful injury prevention could contribute substantially to both short-term and long-term public health.

There are very few (randomised) controlled trials on the effectiveness of preventive interventions for running injuries. A 2011 Cochrane review on prevention of running injuries revealed a total of 25 intervention studies on the prevention of soft-tissue running injury.3 While this presents a …
IMPACT OF INJURY PATTERN DURING TRAINING ON ULTRAMARATHON PERFORMANCE
Authors: M Khodaee, J Spittler, JC Hill, MD Hoffman
Journal: British Journal of Sports Medicine (2014)

Background Little is known about the effect of injuries during training on ultramarathon performance. Objective Determine effects of injuries during training on race performance. Design Observational study using a self-administered pre-race survey. Finish times were obtained from race results posted online. Setting The 2013 Leadville Trail 100 (LT100) and Western States Endurance Run (WSER). Participants Participants of LT100 and WSER 161 km ultramarathons. Risk factor assessment Age, gender, educational level, prior completion of a 161 km ultramarathon, shoe type, self-report of foot strike pattern, and injuries or illnesses interfering with training in the past year were considered. Main outcome measurements The primary outcome measure was whether sustaining an injury or illness resulting in missed training days affected successful completion of an ultramarathon. Results Out of 1206 LT100 and 408 WSER entrants, 893 and 368 completed the pre-race survey (73.9% and 90.1%, respectively). Most participants were male (82%) with average age of 41 years. 52.3% of LT100 and 72.3% of WSER starters finished the races under the 30 hour cutoff time. Among respondents, 40% had masters or higher degrees and 45% reported using dietary supplements on a regular basis. Respondents reported 1432 (multiple answers per runner) injury episodes causing less than a week of missed training and 641 injury episodes causing a week or longer of missed training in the past year. Pain in Achilles (n=196), lower iliotibial band (n=164), upper hamstring (n=115), and groin pain (n=106) were the most common reported issues interfering with training. Only 45 (2.8%) of respondents reported sustaining a stress fracture during training in the past year. Of these, 27 (60%) involved the metatarsals and 10 (22%) involved the tibia. Using a binary logistic regression model, sustaining an injury during the training, age, gender, educational level, prior completion of a 161 km ultramarathon, shoe type, and self-report of foot strike pattern did not affect finish status (P&gt;.05). Conclusions Many ultramarathon runners sustain injuries and illnesses interfering with training schedule, but this does not seem to be a predictor of successfully completing the race.
Induction of cytotoxic T lymphocytes by primary in vitro stimulation with peptides.
Authors: F R Carbone, M W Moore, J M Sheil, M J Bevan
Journal: The Journal of Experimental Medicine (1988)

Antigen-specific cytotoxic T cells can be generated by primary in vitro stimulation of spleen cells from C57BL/6 mice with appropriate peptide fragments. This response can be elicited without prior in vivo immunization. Chicken OVA fragmented with either cyanogen bromide (CN OVA) or trypsin (T OVA) was used as a source of mixed peptides. A synthetic peptide, NP365-380, representing the sequence 365-380 from influenza virus A/PR/8 nucleoprotein, was also used, since this contains the main determinants recognized by CTL generated from H-2b mice infected with A/PR/8 virus. The primary in vitro cytotoxic T cell response was peptide specific, since targets were lysed only in the presence of appropriate peptide antigens. Native OVA could not elicit primary effectors in vitro nor could it sensitize targets for lysis by OVA digest-specific CTL. A synthetic peptide corresponding to residues 111-122 within the OVA sequence could sensitize targets for lysis by effectors induced against T OVA. Effectors generated by in vitro stimulation were CD8+, CD4-, and H-2Db-restricted for NP365-380 and T OVA recognition. CN OVA-specific effectors were also CD8+, CD4-, but surprisingly, were able to lyse a range of H-2-different targets in an antigen-specific manner. These effectors failed to lyse a tumor line that does not express class I MHC molecules. This broad MHC restriction pattern was also apparent at the clonal level. In all cases, the antipeptide CTL generated by primary in vitro stimulation were inefficient in lysing target cells expressing endogenous forms of antigens, such as influenza virus-infected cells or cells transfected with the OVA cDNA. However, cytotoxic T cell lines generated in vitro against the NP365-380 peptide did contain a minor population of virus-reactive cells that could be selectively expanded by stimulation with A/PR/8-infected spleen cells. These results are discussed in terms of class I-restricted T cell stimulation in the absence of antigen processing by high surface densities of peptide/MHC complexes.
A competitive ELISA to detect brevetoxins from Karenia brevis (formerly Gymnodinium breve) in seawater, shellfish, and mammalian body fluid.
Authors: Jerome Naar, Andrea Bourdelais, Carmelo Tomas, Julia Kubanek, Philip L Whitney, Leanne Flewelling, Karen Steidinger, Johnny Lancaster, Daniel G Baden
Journal: Environmental Health Perspectives (2002)

We developed a competitive enzyme-linked immunosorbent assay (ELISA) to analyze brevetoxins, using goat anti-brevetoxin antibodies obtained after immunization with keyhole limpet hemocyanin-brevetoxin conjugates, in combination with a three-step signal amplification process. The procedure, which used secondary biotinylated antibodies, streptavidine-horseradish peroxidase conjugate, and chromogenic enzyme substrate, was useful in reducing nonspecific background signals commonly observed with complex matrices. This competitive ELISA detected brevetoxins in seawater, shellfish extract and homogenate, and mammalian body fluid such as urine and serum without pretreatment, dilution, or purification. We investigated the application of this technique for shellfish monitoring by spiking shellfish meat with brevetoxins and by analyzing oysters from two commercial shellfish beds in Florida that were exposed to a bloom of Karenia brevis (formerly Gymnodinium breve). We performed brevetoxin analysis of shellfish extracts and homogenates by ELISA and compared it with the mouse bioassay and receptor binding assay. The detection limit for brevetoxins in spiked oysters was 2.5 microg/100 g shellfish meat. This assay appears to be a useful tool for neurotoxic shellfish poisoning monitoring in shellfish and seawater, and for mammalian exposure diagnostics, and significantly reduces the time required for analyses.
Alteration of Blood During Acute Hypotension: Effect of Continuous Glass Wool Filtration
Authors: ROY L. SWANK, WOLF H. ISSELHARD, WOLFGANG HISSEN, HANS MERGUET
Journal: Circulation Research (1964)

Acute hypotension was produced in heparinized and nonheparinized dogs by hemorrhage and by injections of histamine, and adhesiveness and aggregation of blood elements determined periodically by the screen filtration pressure method. This method measures the pressure required to force blood at a constant rate through a standardized screen with multiple square holes each 20 x 20 micra. In some cases the arterial blood was perfused through a glass wool filter in an extracorporeal system both before and during periods of hypotension. The results of these studies justify the following conclusions: 1. Increased adhesiveness and aggregation of platelets and other blood elements which occur during hypotension produced by hemorrhage or intravenous injections of histamine were indicated by an increase in the screen filtration pressure of blood. These changes were not prevented from developing, or significantly altered by heparinization of the animal. 2. The amount of blood which could be obtained during arterial hemorrhage was significantly increased by heparinization of the animal. 3. The adhesive and aggregated platelets and leucocytes, which formed during hypotension, were removed from the blood when it was perfused through a column of glass wool. This treatment was attended by a decrease in the screen filtration pressure of the blood to or below normal. 4. The increase in screen filtration pressure which occurred during hypotension was much less marked if the animals' blood had first been circulated through pyrex glass wool. 5. Filtration of blood through pyrex glass wool was also attended by a progressive decrease in the mean arterial blood pressure of the animal.
2012 in Review
Authors: Robert Freedman, David A. Lewis, Robert Michels, Daniel S. Pine, Susan K. Schultz, Carol A. Tamminga, Monifa Seawell
Journal: American Journal of Psychiatry (2012)

TheEdi tors are pleased to offer personal selections of some of the articles they found particularly interesting and important in this year's Journal. Adjusting Insurance for Mental Health CareThe article by Barry et al., "Risk Adjustment in Health Insurance Exchanges for Individuals with Mental Illness" (1), is not light reading for most of our psychiatrist readers.We published this projection of the effects of the Affordable Care Act from a leading group of health care economists because it illustrates the kinds of market decisions that will influence the financing of mental health care in the newly forming state insurance exchanges in the near future.In many states, psychiatrists in their APA district branches may need to advocate for the financing of care, taking into consideration the techniques modeled in this article, specifically reinsurance and risk adjustment to protect the financial viability of insurance plans that serve mentally ill persons.Garfield and Druss (2) point out in an accompanying editorial that these techniques are introduced by the Affordable Care Act to attempt to combat the tendency of plans to restrict mental health care benefits.Plans have a natural tendency to restrict benefits to prevent selection of their insurance plan by the mentally ill patients who need more coverage.The article by Barry et al. illustrates how small differences in these risk adjustment techniques may have profound effects for insurance companies and hence effects on the patients whom they insure.