tbuckley/cabot-search huggingface dataset:
Alterations in Vascular Gene Expression in Invasive Breast Carcinoma
Authors: Belinda S. Parker, Pedram Argani, Brian P. Cook, Han Liangfeng, Scott D. Chartrand, Mindy Zhang, Saurabh Saha, Alberto Bardelli, Yide Jiang, Thia B. St. Martin, Mariana Nacht, Beverly A. Teicher, Katherine W. Klinger, Saraswati Sukumar, Stephen L. Madden
Journal: Cancer Research (2004)

Abstract The molecular signature that defines tumor microvasculature will likely provide clues as to how vascular-dependent tumor proliferation is regulated. Using purified endothelial cells, we generated a database of gene expression changes accompanying vascular proliferation in invasive breast cancer. In contrast to normal mammary vasculature, invasive breast cancer vasculature expresses extracellular matrix and surface proteins characteristic of proliferating and migrating endothelial cells. We define and validate the up-regulated expression of VE-cadherin and osteonectin in breast tumor vasculature. In contrast to other tumor types, invasive breast cancer vasculature induced a high expression level of specific transcription factors, including SNAIL1 and HEYL, that may drive gene expression changes necessary for breast tumor neovascularization. We demonstrate the expression of HEYL in tumor endothelial cells and additionally establish the ability of HEYL to both induce proliferation and attenuate programmed cell death of primary endothelial cells in vitro. We also establish that an additional intracellular protein and previously defined metastasis-associated gene, PRL3, appears to be expressed predominately in the vasculature of invasive breast cancers and is able to enhance the migration of endothelial cells in vitro. Together, our results provide unique insights into vascular regulation in breast tumors and suggest specific roles for genes in driving tumor angiogenesis.
Nationwide survey of comorbidity, use, and costs of all medications in Finnish diabetic individuals.
Authors: A Reunanen, T Kangas, J Martikainen, T Klaukka
Journal: Diabetes Care (2000)

To investigate comorbidity and overall use and costs of medication for all Finnish individuals with diabetes treated with drugs compared with sex- and age-matched control subjects.According to a cross-sectional population study using national registries, 116,224 individuals purchased antidiabetic medications in Finland in 1995. The same number of nondiabetic individuals matched for sex, age, and area of residence were chosen as control subjects. Age at onset of diabetes was used as a criterion for distinguishing between type 1 and type 2 diabetes. The criterion could be applied in 74% of cases. A total of 16,955 individuals were defined as having type 1 diabetes, and 68,517 were defined as having type 2 diabetes. Comorbidity was determined by linkage with a national register including all individuals entitled to special reimbursement for drug treatment for a range of chronic diseases. Data on use and costs of all medications prescribed were obtained from drug purchase records.Cardiovascular diseases and uremia were, as expected, the chronic diseases most closely associated with diabetes. Use of almost all kinds of medication was significantly greater in individuals with type 1 and type 2 diabetes than in control subjects. The greatest differences were observed in relation to cardiovascular drugs and antibiotics. Unexpectedly low use of antiasthmatics was observed in individuals with both types of diabetes, low use of neuroleptics was observed in type 1 diabetic individuals, and low use of hormone replacement therapy was observed in women with type 2 diabetes. Total costs of medications for individuals with diabetes were 3.5 times greater than those for nondiabetic control subjects. The higher costs were mostly attributable to insulin therapy for individuals with type 1 diabetes. The higher costs for individuals with type 2 diabetes were related to the cost of medications other than antidiabetic medication. The possible selection bias in omitting diabetic individuals treated with diet only and individuals in whom diabetes type could not be determined must be considered in interpreting the results.Greater use by and costs of medications for individuals with diabetes than for nondiabetic individuals is related not only to antidiabetic treatment but also to all other kinds of medications. Although drug treatment and the prevalence of several chronic conditions were overall greater in individuals with diabetes versus other individuals, some exceptions merit further study
Introduction to clinical neurology.: 2nd ed. Douglas J Gelb. (Pp 386; pound22.50.) Oxford: Butterworth-Heinemann, 2000. ISBN 07506-7202-1.
Authors: Mark Ridgewell
Journal: British Journal of Sports Medicine (2001)

General practitioners who have long lost the art of performing and applying the findings of a neurological examination will find this concise American text a useful addition to the practice library, as an easily understood reference source.

The book is primarily …
Leukemia inhibitory factor improves survival of retroviral vector-infected hematopoietic stem cells in vitro, allowing efficient long-term expression of vector-encoded human adenosine deaminase in vivo.
Authors: F A Fletcher, K A Moore, M Ashkenazi, P De Vries, P A Overbeek, D E Williams, J W Belmont
Journal: The Journal of Experimental Medicine (1991)

Low recovery and poor retroviral vector infection efficiency of hematopoietic stem cells has hindered application of gene therapy for disease affecting blood-forming tissues. Developmental restriction (or death) of stem cells during ex vivo infection has contributed to these difficulties. In these studies we report that the cytokine leukemia inhibitory factor (LIF) directly or indirectly supported the survival of hematopoietic stem cells during culture of bone marrow with vector-producing fibroblasts, resulting in efficient recovery of stem cells able to compete for engraftment in irradiated recipient animals. The infection efficiency of hematopoietic stem cells recovered from these cultures was approximately 80%; and all recipients (20/20) of the LIF-treated marrow were stably engrafted with the progeny of provirus-bearing stem cells. Expression of vector-encoded human adenosine deaminase (hADA) was detected in all recipients at levels averaging 15-50% of endogenous murine ADA in all their hematolymphoid tissues. Survival of stem cells in untreated cultures was approximately 10% of that observed from LIF-treated cultures, resulting in poor engraftment of recipient animals with transplanted cells. The infection efficiency of the few stem cells recovered from untreated cultures, however, was high (approximately 80%), suggesting that LIF did not have an effect on infection efficiency per se, but acted at the level of stem cell survival. Consistent with the poor engraftment observed in the control animals, expression of vector-encoded ADA was only approximately 4-20% of the endogenous levels. These results support the postulated role of LIF as a regulator of hematopoiesis and suggest that cytokine stimulation can positively affect inefficient retroviral vector transduction in hematopoietic stem cells.
Functional Magnetic Resonance Imaging of Cocaine Craving
Authors: Bruce E. Wexler, Christopher H. Gottschalk, Robert K. Fulbright, Isak Prohovnik, Cheryl M. Lacadie, Bruce J. Rounsaville, John C. Gore
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Identification of brain activity associated with craving is important for understanding the neurobiology of addiction. METHOD: Brain activity was measured in cocaine addicts and healthy subjects by functional magnetic resonance imaging (fMRI) while the subjects watched videotapes designed to elicit happy feelings, sad feelings, or the desire to use cocaine. The subjects indicated the onset of drug craving or emotional response, allowing comparison of groups before and after such feelings. RESULTS: Robust activation of the anterior cingulate was evident in patients watching cocaine-cue tapes but not in patients watching happy or sad tapes or in healthy subjects under any condition. Anterior cingulate activation preceded the reported onset of craving and was evident in patients who did not report craving. In contrast, patients showed less activation than healthy subjects during the cocaine-cue tapes in areas of the frontal lobes. After the reported onset of craving, cocaine-dependent subjects showed greater activity than healthy subjects in regions that are more active in healthy subjects when they watch sad tapes than when they watch happy tapes, suggesting a physiologic link between cocaine-cue responses and normal dysphoric states. Dynamic aspects of regional brain activations, but not the location of activations, were abnormal in cocaine-dependent subjects watching sad tapes, suggesting more general affective dysregulation. Patients showed low activation of sensory areas during initial viewing of all videotapes, suggesting generalized alteration in neuroresponsiveness. CONCLUSIONS: Cocaine cues lead to abnormally high cingulate and low frontal lobe activation in cocaine addicts. Addicts also show more general abnormalities in affect-related brain activation.
Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells
Authors: Kang Liu, Juliana Idoyaga, Anna Charalambous, Shin-ichiro Fujii, Anthony Bonito, Jose Mordoh, Rosa Wainstok, Xue-Feng Bai, Yang Liu, Ralph M. Steinman
Journal: The Journal of Experimental Medicine (2005)

If irradiated tumor cells could be rendered immunogenic, they would provide a safe, broad, and patient-specific array of antigens for immunotherapies. Prior approaches have emphasized genetic transduction of live tumor cells to express cytokines, costimulators, and surrogate foreign antigens. We asked if immunity could be achieved by delivering irradiated, major histocompatibility complex–negative plasmacytoma cells to maturing mouse dendritic cells (DCs) within lymphoid organs. Tumor cells injected intravenously (i.v.) were captured by splenic DCs, whereas subcutaneous (s.c.) injection led only to weak uptake in lymph node or spleen. The natural killer T (NKT) cells mobilizing glycolipid α-galactosyl ceramide, used to mature splenic DCs, served as an effective adjuvant to induce protective immunity. This adjuvant function was mimicked by a combination of poly IC and agonistic αCD40 antibody. The adjuvant glycolipid had to be coadministered with tumor cells i.v. rather than s.c. Specific resistance was generated both to a plasmacytoma and lymphoma. The resistance afforded by a single vaccination lasted &amp;gt;2 mo and required both CD4+ and CD8+ T cells. Mature tumor capturing DCs stimulated the differentiation of P1A tumor antigen-specific, CD8+ T cells and uniquely transferred tumor resistance to naive mice. Therefore, the access of dying tumor cells to DCs that are maturing to activated NKT cells efficiently induces long-lived adaptive resistance.
Human Insulin Analog–Induced Lipoatrophy
Authors: Ximena Lopez, Mariana Castells, Alyne Ricker, Elsa F. Velazquez, Edward Mun, Allison B. Goldfine
Journal: Diabetes Care (2008)

To characterize the pathophysiology of recombinant human insulin-induced lipoatrophy.We performed immunologic laboratory evaluation and skin testing for different insulin analogs and diluents in patients with type 1 diabetes and severe insulin-induced local lipoatrophy. Subcutaneous adipose tissue biopsies of areas of acute (7 days) and chronic insulin administration were examined. Topical sodium cromolyn was applied twice a day to atrophic areas and prophylactically to new sites of insulin administration.Subcutaneous adipose biopsies showed an elevated population of tryptase-positive, chymase-positive degranulated mast cells. Of five patients treated with topical sodium cromolyn, none had new lipoatrophic sites and four showed improvements in old lesions.Tryptase-positive/chymase-postitive mast cells, known to be sensitive to sodium cromolyn, may contribute to the destructive immune process mediated in response to exogenous insulin. Mast cell stabilizing therapy with topical cromolyn may reverse early and prevent new lipoatrophic lesions.
FUNGOUS DEVELOPMENTAL GROWTH FORMS OF BACILLUS INFLUENZÆ
Authors: H. W. Wade, C. Manalang
Journal: The Journal of Experimental Medicine (1920)

It has been found that three different strains of an organism supposed to be Bacillus influenzae will, under certain conditions, abandon the usual bacillary form and grow as a frank fungus, morphologically of the Discomyces type. Under other conditions they show less modification, the most striking feature then being the production of conidiospores, bodies of a type not found in true bacteria. That this organism may not be the true Pfeiffer bacillus is conceivable, of course, but considering the source, morphology, ordinary cultural characteristics, and the poison production of the one strain tested, we consider this highly improbable. Further, we are confident that the cultures do not contain any contaminating organisms, as may be suggested. In short, we believe that we have been dealing solely with the true Pfeiffer bacillus. While these observations are of considerable interest as a contribution to the biology of the bacteria of this general type it cannot, of course, be predicted that they will prove to be of any significance as regards the true causative agent of epidemic influenza. Experimental work with this organism, apparently negative so far as reproducing true clinical influenza is concerned, has been carried out with the bacillary form exclusively. It may be found that its physiological capabilities in another phase are essentially different. This is a general biological law and there is no evident reason why it should not hold true here. It remains to be determined whether the relatively high, complex forms described have any relation to those that occur while the organism lives among other organisms on the respiratory mucosa or acts as a tissue invader. While it seems improbable that they should develop in the animal body, that is while the organism is living as a parasite, it is at least possible that the bacillus may, under some conditions, undergo some analogous or at least similarly radical modification. If this supposition is true its cultivability might well be quite different from that of its bacillary phase, in which event it might be present in abundance and yet not be found in ordinary cultures or be recognizable in films. But the more important problem would appear to be whether it can assume a simpler phase. If, as some believe, some of the infectious bacteria and fungi can do this, whether it be as minute, filter-passing, formed elements or as a more or less amorphous ("sym-plastic,"(16) "crytoplasmic,"(15)) substance, an organism that is capable of as remarkable a range of morphological development upward might well go to the other extreme from the mean, bacillary stage. Whether or not this occurs and if so under what conditions are questions that deserve through investigation.
Is the measurement of maximal oxygen intake passé?
Authors: Roy J Shephard
Journal: British Journal of Sports Medicine (2008)

A recent and controversial review1 suggests that the measurement of maximal oxygen intake is passe. The author concludes (p. 554) “ It is now time to develop novel testing methods....That the measured VO2max is a relatively poor predictor of both the performance potential of athletes with similar athletic ability and of the changes in performance that occur with continued training should encourage both basic and applied sports scientists to reconsider the real value of this iconic test. ”

A number of the arguments that are advanced in this review seem to need correction or refutation. Specifically, this riposte will examine whether a maximal treadmill test is an unrealistic procedure for athletes, whether a unimodal approach to testing is appropriate in sports medicine, and whether an alternative laboratory test will be developed to categorise the performance of individual athletes. Comments will also be made on the place of maximal oxygen intake assessment in various areas of science, sports medicine and clinical medicine.

Noakes argues1 that the treadmill test is an unrealistic approach to the testing of athletes for three reasons: the duration of the exercise is not known to the subject, there is a steep and progressive increase in the intensity of exercise, and the person who is tested has no control over the ultimate intensity of effort. All of these criticisms may be true of the test protocol used in some laboratories. However, the standard recommendation is for a treadmill test lasting 9–11 minutes, and this should be explained to the subject. The appropriate treadmill slope and speed should be ascertained by preliminary submaximal testing; this allows the definitive test to commence close to maximal steady-state effort, thereby avoiding a steep ramp of intensity. Moreover, the maximal …
Model-driven analysis of experimentally determined growth phenotypes for 465 yeast gene deletion mutants under 16 different conditions
Authors: Evan S Snitkin, Aimée M Dudley, Daniel M Janse, Kaisheen Wong, George M Church, Daniel Segrè
Journal: Genome biology (2008)

Understanding the response of complex biochemical networks to genetic perturbations and environmental variability is a fundamental challenge in biology. Integration of high-throughput experimental assays and genome-scale computational methods is likely to produce insight otherwise unreachable, but specific examples of such integration have only begun to be explored. In this study, we measured growth phenotypes of 465 Saccharomyces cerevisiae gene deletion mutants under 16 metabolically relevant conditions and integrated them with the corresponding flux balance model predictions. We first used discordance between experimental results and model predictions to guide a stage of experimental refinement, which resulted in a significant improvement in the quality of the experimental data. Next, we used discordance still present in the refined experimental data to assess the reliability of yeast metabolism models under different conditions. In addition to estimating predictive capacity based on growth phenotypes, we sought to explain these discordances by examining predicted flux distributions visualized through a new, freely available platform. This analysis led to insight into the glycerol utilization pathway and the potential effects of metabolic shortcuts on model results. Finally, we used model predictions and experimental data to discriminate between alternative raffinose catabolism routes. Our study demonstrates how a new level of integration between high throughput measurements and flux balance model predictions can improve understanding of both experimental and computational results. The added value of a joint analysis is a more reliable platform for specific testing of biological hypotheses, such as the catabolic routes of different carbon sources.
Adult Treatment Panel III 2001 but Not International Diabetes Federation 2005 Criteria of the Metabolic Syndrome Predict Clinical Cardiovascular Events in Subjects Who Underwent Coronary Angiography
Authors: Christoph H. Saely, Lorena Koch, Fabian Schmid, Thomas Marte, Stefan Aczel, Peter Langer, Guenter Hoefle, Heinz Drexel
Journal: Diabetes Care (2006)

The International Diabetes Federation (IDF) has recently established a worldwide consensus definition of the metabolic syndrome. No prospective data are available on the cardiovascular risk associated with this new metabolic syndrome definition.In a prospective study of 750 coronary patients, we recorded vascular events over 4 years.From our patients, 37.3% (n = 280) had the metabolic syndrome according to the Adult Treatment Panel III (ATPIII) definition and 45.5% (n = 341) according to the IDF definition. The metabolic syndrome as defined by the ATPIII criteria significantly predicted vascular events (adjusted hazard ratio 1.745 [95% CI 1.255-2.427]; P = 0.001), but the metabolic syndrome as defined by IDF criteria did not (1.189 [0.859-1.646]; P = 0.297). Accordingly, event-free survival was significantly lower among patients who fulfilled the ATPIII but not the IDF criteria than among those who met the IDF but not the ATPIII criteria (P = 0.012). The metabolic syndrome as defined by ATPIII criteria remained significantly predictive of vascular events after adjustment for type 2 diabetes but not after additional adjustment for the metabolic syndrome components high triglycerides and low HDL cholesterol. These lipid traits in turn proved significantly predictive of vascular events even after adjustment for the metabolic syndrome.The ATPIII definition of the metabolic syndrome confers a significantly higher risk of vascular events than the IDF definition. However, among angiographied coronary patients, even the ATPIII definition of the metabolic syndrome does not provide prognostic information beyond its dyslipidemic features.
Signal Transducer and Activator of Transcription 3 Is a Key Regulator of Keratinocyte Survival and Proliferation following UV Irradiation
Authors: Shigetoshi Sano, Keith Syson Chan, Masahiro Kira, Ken Kataoka, Satoshi Takagi, Masahito Tarutani, Satoshi Itami, Kaoru Kiguchi, Masayuki Yokoi, Kaoru Sugasawa, Toshio Mori, Fumio Hanaoka, Junji Takeda, John DiGiovanni
Journal: Cancer Research (2005)

Abstract UVB irradiation of signal transducer and activator of transcription 3 (Stat3)–deficient keratinocytes resulted in a high incidence of apoptosis compared with controls. Conversely, forced expression of Stat3 desensitized keratinocytes to UVB-induced apoptosis. Upon UVB exposure, keratinocyte Stat3 was rapidly dephosphorylated, followed by decreases of both Stat3 mRNA and protein levels in a p53-independent manner. Vanadate treatment reversed the UVB-induced down-regulation of Stat3 and generation of apoptotic keratinocytes, suggesting the involvement of a tyrosine phosphatase. Furthermore, Stat3 was required for UVB-induced proliferation of follicular keratinocytes, leading to epidermal thickening. Finally, constitutive activation of Stat3 was observed in UVB-induced squamous cell carcinomas of either mice or human origin. These data suggest that Stat3 is required for survival and proliferation of keratinocytes following UVB exposure and that Stat3 is tightly regulated as part of a novel protective mechanism against UVB-induced skin cancer.