tbuckley/cabot-search huggingface dataset:
THE KELOID OVARY
Authors: T. C. Clare
Journal: BMJ (1931)

Under x rays such a condition will show a filling defect, and fixation of the colon.Recently at operatiotn on two cases of this type there was found in both a section of the colon wall, several inches in length, acutely inflamed and densely thickened, with the minute diverticula bulging through the peritoneum.The condition resembled a sort of cellulitis of the bowel wall.When there is a simple diverticulosis we have noticed that if photographs taken at different periods are com- pared fresh diverticula can usually be seen, and that some of the previouslv existing ones are larger.From a study of a number of such cases it seems that, while inflamnmatory complications may be held in check and often made to retrogress by appropriate treatment, it is not possible to prevent the diverticula from becoming larger or to make them decrease in number uinless the faecal contents are deflected from the affected area by a colostomy or short circuit.From the patient's point of view the diverticula do not cause any symptoms as long as inflammatory complicatioins can be avoided.Unfor- tunately, patients tend to get careless when they have no svmptoms, and they think they are quite well and need not continue the treatment.This too often results in acute complications, which may be disastrous.One patient, after-being quite well for several years, perforated suddenly while travelling from Paris to London, and died from acute peritonitis.Arnother patient suddenly developed a perforation into the bladder.
Rabbit antithymocyte globulin–induced serum sickness disease and human kidney graft survival
Authors: Grégoire Couvrat-Desvergnes, Apolline Salama, Ludmilla Le Berre, Gwénaëlle Evanno, Ondrej Viklicky, Petra Hruba, Pavel Vesely, Pierrick Guerif, Thomas Dejoie, Juliette Rousse, Arnaud Nicot, Jean-Marie Bach, Evelyn Ang, Yohann Foucher, Sophie Brouard, Stéphanie Castagnet, Magali Giral, Jean Harb, Hélène Perreault, Béatrice Charreau, Marine Lorent, Jean-Paul Soulillou
Journal: Journal of Clinical Investigation (2015)

Rabbit-generated antithymocyte globulins (ATGs), which target human T cells, are widely used as immunosuppressive agents during treatment of kidney allograft recipients. However, ATGs can induce immune complex diseases, including serum sickness disease (SSD). Rabbit and human IgGs have various antigenic differences, including expression of the sialic acid Neu5Gc and α-1-3-Gal (Gal), which are not synthesized by human beings. Moreover, anti-Neu5Gc antibodies have been shown to preexist and be elicited by immunization in human subjects. This study aimed to assess the effect of SSD on long-term kidney allograft outcome and to compare the immunization status of grafted patients presenting with SSD following ATG induction treatment.We analyzed data from a cohort of 889 first kidney graft recipients with ATG induction (86 with SSD [SSD(+)] and 803 without SSD [SSD(-)]) from the Données Informatisées et Validées en Transplantation data bank. Two subgroups of SSD(+) and SSD(-) patients that had received ATG induction treatment were then assessed for total anti-ATG, anti-Neu5Gc, and anti-Gal antibodies using ELISA assays on sera before and after transplantation.SSD was significantly associated with long-term graft loss (>10 years, P = 0.02). Moreover, SSD(+) patients exhibited significantly elevated titers of anti-ATG (P = 0.043) and anti-Neu5Gc (P = 0.007) IgGs in late post-graft samples compared with SSD(-) recipients.In conclusion, our data indicate that SSD is a major contributing factor of late graft loss following ATG induction and that anti-Neu5Gc antibodies increase over time in SSD(+) patients.This study was funded by Société d'Accélération du Transfert de Technologies Ouest Valorisation, the European FP7 "Translink" research program, the French National Agency of Research, Labex Transplantex, the Natural Science and Engineering Research Council of Canada, and the Canadian Foundation for Innovation.
Pharmacogenetics — Tailoring Treatment for the Outliers
Authors: Janet Woodcock, Lawrence J. Lesko
Journal: New England Journal of Medicine (2009)

If it were not for the great variability among individuals, medicine might as well be a science and not an art.— Sir William Osler (1892)Over the past half century, biomedical science has developed randomized, controlled clinical-trial methods that can distinguish treatment effects from the noise of human variability. Positive results from tests of a treatment in a randomized, controlled trial provide great confidence that an intervention improves a prespecified outcome in a population defined by explicit entry criteria. These methods are rightly venerated because they have helped move medicine from anecdote to science and have largely brought about . . .
Metabolic syndrome in systemic lupus erythematosus: lower prevalence in Brazil than in the USA
Authors: G. D Azevedo, R. G N Gadelha, M. J. Vilar
Journal: Annals of the Rheumatic Diseases (2007)

We read with great interest the recent article by Chung et al on the high prevalence of metabolic syndrome (MetS) in patients with systemic lupus erythematosus (SLE).1 This topic is extremely relevant as regards the current clinical management of patients with SLE, since findings from several studies point to increased cardiovascular risk associated with this disease.2–4 As with most previous research on the incidence of MetS, this study was conducted in the American population where the prevalence of obesity is higher than in other countries.1 However, it is very important to consider the results from studies conducted in different populations when analysing the influence of obesity and other …
AUC-guided dosing of tacrolimus prevents progressive systemic overexposure in renal transplant recipients
Authors: Eduard M. Scholten, Serge C.L.M. Cremers, Rik C. Schoemaker, Ajda T. Rowshani, Erik J. van Kan, J.A.N. den Hartigh, Leendert C. Paul, Johan W. de Fijter
Journal: Kidney International (2005)
Career destinations, views and future plans of the UK medical qualifiers of 1988
Authors: Kathryn Taylor, Trevor Lambert, Michael Goldacre
Journal: Journal of the Royal Society of Medicine (2010)

Summary Objectives To report the career destinations, views and future plans of a cohort of senior doctors who qualified in the 1980s. Methods Postal questionnaire survey of all doctors who qualified from all UK medical schools in 1988. Results The response rate was 69%. We estimated that 81% of the total cohort was working in the NHS, 16 years after qualification; and that at least 94% of graduates who, when students, were from UK homes, were working in medicine. Of NHS doctors, 30% worked part-time. NHS doctors rated their job satisfaction highly (median score 19.9, scale 5–25) but were less satisfied with the amount of leisure time available to them (median score 5.4, scale 1–10). NHS doctors were very positive about their careers, but were less positive about working hours and some other aspects of the NHS. Women were more positive than men about working conditions; general practitioners were more positive than hospital doctors. Twenty-five percent reported unmet needs for further training or career-related advice, particularly about career development. Twenty-nine percent intended to reduce their hours in future, while 6%, mainly part-time women, planned to increase their hours. Overall, 10% of NHS doctors planned to do more service work in future and 24% planned to do less; among part-time women, 18% planned to do more and only 14% less. Conclusions These NHS doctors, now in their 40s, had a high level of satisfaction with their jobs and their careers but were less satisfied with some other aspects of their working environment. A substantial percentage had expectations about future career development and change.
Requirement for the L-type Ca2+ channel α1D subunit in postnatal pancreatic β cell generation
Authors: Yoon Namkung, Nataliya Skrypnyk, Myung-Jin Jeong, Taehoon Lee, Myung-Shik Lee, Hyung-Lae Kim, Hemin Chin, Pann-Ghill Suh, Sung-Sook Kim, Hee-Sup Shin
Journal: Journal of Clinical Investigation (2001)

Pancreatic β cells are the source of insulin, which directly lowers blood glucose levels in the body. Our analyses of α1D gene-knockout (α1D–/–) mice show that the L-type calcium channel, α1D, is required for proper β cell generation in the postnatal pancreas. Knockout mice were characteristically slightly smaller than their littermates and exhibited hypoinsulinemia and glucose intolerance. However, isolated α1D–/– islets persisted in glucose sensing and insulin secretion, with compensatory overexpression of another L-type channel gene, α1C. Histologically, newborn α1D–/– mice had an equivalent number of islets to wild-type mice. In contrast, adult α1D–/– mice showed a decrease in the number and size of islets, compared with littermate wild-type mice due to a decrease in β cell generation. TUNEL staining showed that there was no increase in cell death in α1D–/– islets, and a 5-bromo-2′ deoxyuridine-labeling (BrdU-labeling) assay illustrated significant reduction in the proliferation rate of β cells in α1D–/– islets.
Natural occurrence and origin of somatically mutated memory B cells in mice.
Authors: B Schittek, K Rajewsky
Journal: The Journal of Experimental Medicine (1992)

While most murine peripheral B cells express germline-encoded antibodies of classes M and D (mu+ delta+ cells), small numbers of memory B cells expressing somatically mutated immunoglobulin G antibodies are generated upon T cell-dependent immunization. Analyzing the antibody repertoire of the mu-delta- B cell pool in unimmunized mice, we show that these cells express somatically mutated VH genes and that most of these genes derive from a set of germline VH genes dominantly expressed by mu+delta+ B cells. Thus, class-switched memory B cells are generated in the absence of intentional immunization, presumably in response to environmental antigens. These cells are either recruited from mu+delta+ B cells or selected from newly arising B cells in parallel to the latter, by the same antigens.
Globular Adiponectin Activates Nuclear Factor- B in Vascular Endothelial Cells, Which in Turn Induces Expression of Proinflammatory and Adhesion Molecule Genes
Authors: Y. Hattori
Journal: Diabetes Care (2006)

Adiponectin is present in serum in trimer, hexamer, or high–molecular weight (HMW) form. A proteolytic cleavage product of adiponectin, known as globular adiponectin, has also been found to circulate in human plasma (1). The biological activities of these isoforms is controversial. It has been shown that recombinant globular adiponectin is pharmacologically active and induces free fatty acid oxidation in incubated mouse muscle and cultured muscle cells (1). Yamauchi et al. (2) have reported significantly greater potency of globular adiponectin in reversing insulin resistance than uncleaved adiponectin. However, it has recently been proposed that the ratio of HMW to total adiponectin, but not the absolute amounts of adiponectin, determines insulin sensitivity in humans and rodents (3). Clinical data also confirmed that patients with type 2 diabetes and coronary heart diseases have a selective reduction in HMW adiponectin (3,4). The experimental and clinical data collectively suggest that the oligomeric complex distribution of adiponectin is critical for the antidiabetes and antiatherogenic activity of this hormone (4).

We thus questioned how globular adiponectin alters the gene expression in human umbilical vein endothelial cells (HUVECs). First, we confirmed the adiponectin receptor 1 gene expression in HUVECs, which have a high …
<i>TMPRSS2:ERG</i> Fusion-Associated Deletions Provide Insight into the Heterogeneity of Prostate Cancer
Authors: Sven Perner, Francesca Demichelis, Rameen Beroukhim, Folke H. Schmidt, Juan-Miguel Mosquera, Sunita Setlur, Joelle Tchinda, Scott A. Tomlins, Matthias D. Hofer, Kenneth G. Pienta, Rainer Kuefer, Robert Vessella, Xiao-Wei Sun, Matthew Meyerson, Charles Lee, William R. Sellers, Arul M. Chinnaiyan, Mark A. Rubin
Journal: Cancer Research (2006)

Abstract Prostate cancer is a common and clinically heterogeneous disease with marked variability in progression. The recent identification of gene fusions of the 5′-untranslated region of TMPRSS2 (21q22.3) with the ETS transcription factor family members, either ERG (21q22.2), ETV1 (7p21.2), or ETV4 (17q21), suggests a mechanism for overexpression of the ETS genes in the majority of prostate cancers. In the current study using fluorescence in situ hybridization (FISH), we identified the TMPRSS2:ERG rearrangements in 49.2% of 118 primary prostate cancers and 41.2% of 18 hormone-naive lymph node metastases. The FISH assay detected intronic deletions between ERG and TMPRSS2 resulting in TMPRSS2:ERG fusion in 60.3% (35 of 58) of the primary TMPRSS2:ERG prostate cancers and 42.9% (3 of 7) of the TMPRSS2:ERG hormone-naive lymph node metastases. A significant association was observed between TMPRSS2:ERG rearranged tumors through deletions and higher tumor stage and the presence of metastatic disease involving pelvic lymph nodes. Using 100K oligonucleotide single nucleotide polymorphism arrays, a homogeneous deletion site between ERG and TMPRSS2 on chromosome 21q22.2-3 was identified with two distinct subclasses distinguished by the start point of the deletion at either 38.765 or 38.911 Mb. This study confirms that TMPRSS2:ERG is fused in approximately half of the prostate cancers through deletion of genomic DNA between ERG and TMPRSS2. The deletion as cause of TMPRSS2:ERG fusion is associated with clinical features for prostate cancer progression compared with tumors that lack the TMPRSS2:ERG rearrangement. (Cancer Res 2006; 66(17): 8337-41)
Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells
Authors: Deborah H. Strickland, Philip A. Stumbles, Graeme R. Zosky, Lily S. Subrata, Jenny A. Thomas, Debra J. Turner, Peter D. Sly, Patrick G. Holt
Journal: The Journal of Experimental Medicine (2006)

An important feature of atopic asthma is the T cell–driven late phase reaction involving transient bronchoconstriction followed by development of airways hyperresponsiveness (AHR). Using a unique rat asthma model we recently showed that the onset and duration of the aeroallergen-induced airway mucosal T cell activation response in sensitized rats is determined by the kinetics of functional maturation of resident airway mucosal dendritic cells (AMDCs) mediated by cognate interactions with CD4+ T helper memory cells. The study below extends these investigations to chronic aeroallergen exposure. We demonstrate that prevention of ensuing cycles of T cell activation and resultant AHR during chronic exposure of sensitized rats to allergen aerosols is mediated by CD4+CD25+Foxp3+LAG3+ CTLA+CD45RC+ T cells which appear in the airway mucosa and regional lymph nodes within 24 h of initiation of exposure, and inhibit subsequent Th-mediated upregulation of AMDC functions. These cells exhibit potent regulatory T (T reg) cell activity in both in vivo and ex vivo assay systems. The maintenance of protective T reg activity is absolutely dependent on continuing allergen stimulation, as interruption of exposure leads to waning of T reg activity and reemergence of sensitivity to aeroallergen exposure manifesting as AMDC/T cell upregulation and resurgence of T helper 2 cytokine expression, airways eosinophilia, and AHR.
Electrolyte-Labile Increase of Oxygen Affinity during In Vivo Aging of Hemoglobin*
Authors: Miles J. Edwards, Demetrios A. Rigas
Journal: Journal of Clinical Investigation (1967)

Normal human erythrocytes were separated according to in vivo age by ultracentrifugation. The “young” and “old” erythrocytes had mean cell ages of approximately 40 and 79 days, respectively. “Young” erythrocytes had a lower oxygen affinity and a higher heme-heme interaction than did “old” erythrocytes. This indicates an impairment of the oxygen-carrying function of erythrocyte hemoglobin with age.
Phase II Study of Bevacizumab in Combination with Sorafenib in Recurrent Glioblastoma (N0776): A North Central Cancer Treatment Group Trial
Authors: Evanthia Galanis, S. Keith Anderson, Jackie M. Lafky, Joon H. Uhm, Caterina Giannini, Shaji K. Kumar, Teresa K. Kimlinger, Donald W. Northfelt, Patrick J. Flynn, Kurt A. Jaeckle, Timothy J. Kaufmann, Jan C. Buckner
Journal: Clinical Cancer Research (2013)

We hypothesized that vertical blockade of VEGF signaling by combining bevacizumab with sorafenib in patients with recurrent glioblastoma would result in a synergistic therapeutic effect. We also investigated whether VEGF, VEGFR2 and hypoxia-inducible factor-1α single-nucleotide polymorphisms (SNP), circulating biomarkers of angiogenesis, and MRI markers such as apparent diffusion coefficient (ADC) are correlated with treatment efficacy and/or toxicity.Patients received bevacizumab (5 mg/kg every 2 weeks) with sorafenib (200 mg twice a day, weekly, days 1-5; group A). Due to toxicity, the starting sorafenib dose was subsequently modified to 200 mg every day (group B).Fifty-four patients were enrolled: 19 patients in group A and 35 in group B. Objective response rate was 18.5% with median duration of 6.7 months (range 0.5-24.1 months). Six-month progression-free survival (PFS6) was 20.4% (11/54), and median overall survival (OS) was 5.6 months [95% confidence interval (CI), 4.7-8.2]; outcome was similar between the two dose groups. We identified SNPs in the VEGF and VEGFR2 promoter regions, which were associated with PFS6 (P<0.022). Among molecular markers of angiogenesis, a higher log2 baseline level of stromal cell-derived factor-1 was associated with PFS6 success (P=0.04). Circulating endothelial cells decreased during treatment with subsequent increase at disease progression (P=0.022). Imaging analysis showed a trend associating ADC-L with poor outcome.The bevacizumab/sorafenib combination did not improve outcome of patients with recurrent glioblastoma versus historic bevacizumab-treated controls. Biologic markers of response and resistance to bevacizumab in gliomas were identified which merit prospective validation.
Relationship between training-playing loads and injury risk in elite australian footballers
Authors: D Buttifant, J Berry, S Ullah, C F Finch
Journal: British Journal of Sports Medicine (2011)

Background Training and match loads are important for ensuring optimal performance outcomes and achievements of footballers and also have an impact on injury and illness among the players. There had been no prospective study of the training/playing loads of first year Australian Football League (AFL) players and associated influence on injury rates. Objectives To measure the training and match loads and determine the relationship between loads and injury risk in the first year AFL football players and then compare this to mature 3+ years AFL players. Design Data was collected through a systematic prospective documentation of the 2009 training-playing loads in all first year AFL players, and a subset of 3+ years players. Data was collected by the club's conditioning or sport science staff weekly for the 2009 competitive season. Results 64 first year and 58 3+ years players from nine of the 16 AFL clubs were participated in the study. The first year players had significantly higher injury incidence and prevalence rates compared to 3+ years players, leading to both missed matches and missed training sessions. By the end of the 22 matches of the competitive season, the first year players had collectively missed 4.3 times as many matches and 2.6 times as many training sessions as the 3+ years players due to injury. When the number of players available at any competition week was taken into account, the first year players were 14.3 times more likely to miss matches. Conclusions There was a significantly increased injury risk for first year players compared to more mature AFL players resulting in more missed matches and training sessions.
The Risks and Benefits of 5α-Reductase Inhibitors for Prostate-Cancer Prevention
Authors: Marc R. Theoret, Yang-Min Ning, Jenny J. Zhang, Robert Justice, Patricia Keegan, Richard Pazdur
Journal: New England Journal of Medicine (2011)

5α-reductase inhibitors' potential benefits in preventing prostate cancer and potential increased risk for high-grade cancers have been central issues for the FDA, which convened its Oncologic Drugs Advisory Committee to address the topic last December.
cGMP-Dependent Relaxation of Smooth Muscle Is Coupled With the Change in the Phosphorylation of Myosin Phosphatase
Authors: Kensei Nakamura, Yasuhiko Koga, Hiroyasu Sakai, Kazuaki Homma, Mitsuo Ikebe
Journal: Circulation Research (2007)

Nitric oxide/cGMP pathway induces vasodilatation, yet the underlying mechanism is obscure. In the present study, we studied the mechanism of cGMP-induced relaxation of the smooth muscle contractile apparatus using permeabilized rabbit femoral arterial smooth muscle. 8-Br-cGMP-induced relaxation was accompanied with a decrease in myosin light chain (MLC) phosphorylation. MLC phosphatase (MLCP) activity, once decreased by agonist-stimulation, recovered to the resting level on addition of 8-Br-cGMP. Because MLCP activity is regulated by the phosphorylation of a MLCP-specific inhibitor, CPI17 at Thr38 and MBS (myosin binding subunit of MLCP) at Thr696, we examined the effect of 8-Br-cGMP on the phosphorylation of these MLCP modulators. Whereas CPI17 phosphorylation was unchanged after addition of 8-Br-cGMP, MBS phosphorylation at Thr696 was significantly decreased by 8-Br-cGMP. We found that 8-Br-cGMP markedly increased MBS phosphorylation at Ser695 in the fiber pretreated with phenylephrine. MBS phosphorylation of Thr696 phosphorylated MBS at Ser695 partially resumed MLCP activity inhibited by Thr696 phosphorylation. Whereas Ser695 phosphorylation was markedly increased, the extent of diphosphorylated MBS at Ser695 and Thr696 in fibers was unchanged after cGMP-stimulation. We found that MBS phosphatase activity in arteries for both diphosphorylated MBS and monophosphorylated MBS at Thr696 significantly increased by 8-Br-cGMP, whereas MBS kinase activity was unchanged. These results suggest that the phosphorylation at Ser640 induced by cGMP shifted the equilibrium of the Thr641 phosphorylation toward dephosphorylation, thus increasing MLCP activity. This results in the decrease in MLC phosphorylation and smooth muscle relaxation.
The association between resting and mild-to-moderate exercise pulmonary artery pressure
Authors: K. Whyte, S. Hoette, P. Herve, D. Montani, X. Jaïs, F. Parent, L. Savale, D. Natali, D.S. O'Callaghan, G. Garcia, O. Sitbon, G. Simonneau, M. Humbert, D. Chemla
Journal: European Respiratory Journal (2011)

The mean pulmonary artery pressure (P(pa)) achieved on mild-to-moderate exercise is age related and its haemodynamic correlates remain to be documented in patients free of pulmonary hypertension (PH). Our retrospective study involved patients free of PH investigated in our centre for possible pulmonary vascular disease between January 1, 2007 and October 31, 2009 who underwent right heart catheterisation at rest and during supine exercise up to 60 W. The 38 out of 99 patients aged <50 yrs were included and a P(pa) of 30 mmHg was considered the upper limit of normal on exercise. The 24 subjects who developed P(pa)>30 mmHg on exercise had higher resting P(pa) (19±3 versus 15±4 mmHg) and indexed pulmonary vascular resistance (PVRi; 3.4±1.5 versus 2.2±1.1 WU·m(2); p<0.05) than the remaining 14 subjects. Resting P(pa) >15 mmHg predicted exercise P(pa) >30 mmHg with 88% sensitivity and 57% specificity. The eight patients with resting P(pa) 22-24 mmHg all had exercise P(pa) >30 mmHg. In subjects aged <50 yrs investigated for possible pulmonary vascular disease and free of PH, patients with mild-to-moderate exercise P(pa) >30 mmHg had higher resting PVRi and higher resting P(pa), although there was no resting P(pa) threshold value that could predict normal response on mild-to-moderate exercise. The clinical relevance of such findings deserves further long-term follow-up studies.