tbuckley/cabot-search huggingface dataset:
Altered norepinephrine turnover in the brown fat of rats with chronic renal failure.
Authors: R Bigazzi, E Kogosov, V M Campese
Journal: Journal of the American Society of Nephrology (1994)

Disturbances of the sympathetic nervous system (SNS) have been described in chronic renal failure, but their role in the metabolic derangements of uremia has not been well established. In these studies, SNS activity has been measured in the ventromedial hypothalamic (VMH) nuclei and in the intercostal brown adipose tissue (IBAT) of Sprague Dawley 5/6 nephrectomized or sham-operated rats. SNS activity was determined by calculating the norepinephrine (NE) turnover rate (in picograms per milligram per hour) 3, 6, and 12 h after the inhibition of NE synthesis with L-methyltyrosine. The endogenous NE concentration was significantly (P < 0.01) higher in the VMH (14,567 +/- 1,130 pg/mg wet wt) and IBAT (17,902 +/- 2,308 pg/mg wet wt) of uremic than control rats (9,600 +/- 1,110 and 5,752 +/- 320 pg/mg wet wt, respectively). The turnover rates of NE in the VMH (582 +/- 146 pg/mg per hour) and in the IBAT (1,432 +/- 179 pg/mg/hr) of uremic rats were significantly faster (P < 0.01) than in control rats (192 +/- 96 and 173 +/- 58 pg/mg per hour, respectively). These studies demonstrate a significant increase in NE turnover in the VMH nuclei and IBAT of uremic rats. It is suggested that increased efferent sympathetic nerve discharge from the VMH to the IBAT may play a role in the pathogenesis of malnutrition in uremia.
Long term follow up study of survival associated with cleft lip and palate at birth
Authors: Kaare Christensen, Knud Juel, Anne Maria Herskind, Jeffrey C Murray
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To assess the overall and cause specific mortality of people from birth to 55 years with cleft lip and palate. <b>Design</b> Long term follow up study. <b>Setting</b> Danish register of deaths. <b>Participants</b> People born with cleft lip and palate between 1943 and 1987, followed to 1998. <b>Main outcome measures</b> Observed and expected numbers of deaths, summarised as overall and cause specific standardised mortality ratios. <b>Results</b> 5331 people with cleft lip and palate were followed for 170 421 person years. The expected number of deaths was 259, but 402 occurred, corresponding to a standardised mortality ratio of 1.4 (95% confidence interval 1.3 to 1.6) for males and 1.8 (1.5 to 2.1) for females. The increased risk of mortality was nearly constant for the three intervals at follow up: first year of life, 1-17 years, and 18-55 years. The participants had an increased risk of all major causes of death. <b>Conclusions</b> People with cleft lip and palate have increased mortality up to age 55. Children born with cleft lip and palate and possibly other congenital malformations may benefit from specific preventive health measures into and throughout adulthood.
Racial stereotyping: survey of psychiatrists in the United Kingdom
Authors: H. Minnis, A. McMillan, M. Gillies, S. Smith
Journal: BMJ (2001)

Ten years ago, psychiatrists rated black male patients as potentially more violent than white patients.1 We aimed to establish whether such racial stereotyping still occurs.

We sent a postal questionnaire concerning the first presentation of a young man at casualty—which included a photograph, brief history, and findings on the patient's mental state—to a random sample (generated by SPSS statistical software) of 1000 British psychiatrists obtained from the Royal College of Psychiatrists' database. The sample was randomised so that half received a picture of a black man and half received a picture of a white man. (Photographs were of one of four healthy volunteers, whom we had not seen previously; they were matched for age and occupation, and photographed under identical conditions.) To exclude the possibility that results stemmed from differences between individual photographs, such as facial expression and mode of dress, we photographed two men from each race; one was a footballer and the other an academic (the photographs can be seen on BMJ 's …
Mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma
Authors: A. Imada, N. Shijubo, H Kojima, S Abe
Journal: European Respiratory Journal (2000)

Angiogenesis is in part related to mast cells. However, the biological significance of mast cells within lung carcinoma remains unclear. Immunohistochemistry was used to stain for tryptase, CD34 and vascular endothelial growth factor (VEGF) in 85 cases of stage I nonsmall cell lung carcinoma. VEGF was found in 33 of 53 adenocarcinomas and 14 of 32 squamous cell carcinomas. Cases of adenocarcinoma had significantly higher mast cell counts than those of squamous cell carcinoma. In adenocarcinoma, mast cell counts in VEGF-positive tumours were significantly higher than in VEGF-negative tumours, whereas in squamous cell carcinoma they were not. Good correlation was observed between intratumoural mast cell counts and microvessel counts. Double staining showed most intratumoural mast cells expressed VEGF. Importantly, only in lung adenocarcinoma, members in the high mast cell count group had significantly worse prognosis than those in the low mast cell count group. It is concluded that tumour-released vascular endothelial growth factors may be related to mast cell accumulation, intratumoural mast cells may produce vascular endothelial growth factor, and stromal mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma.
Tumor Response and Toxicity of Neoadjuvant Erlotinib in Patients With Early-Stage Non–Small-Cell Lung Cancer
Authors: Eva E. Schaake, Ingrid Kappers, Henk E. Codrington, Renato A. Valdés Olmos, Hendrik J. Teertstra, Renée van Pel, Jacobus A. Burgers, Harm van Tinteren, Houke M. Klomp
Journal: Journal of Clinical Oncology (2012)

Purpose The development of targeted therapy has introduced new options to improve treatment outcome in selected patients. The objective of this prospective study was to investigate the safety of preoperative erlotinib treatment and the (in vivo) response in patients with early-stage resectable non–small-cell lung cancer (NSCLC). Patients and Methods This study was designed as an open-label phase II trial, performed in four hospitals in the Netherlands, according to a Simon's minimax two-stage procedure. Initially, operable patients with early-stage NSCLC (n = 15) were entered from an enriched population (never-smoker, female sex, nonsquamous histology, or Asian ethnicity); thereafter, unselected patients were included to a total of N = 60. Patients received preoperative erlotinib 150 mg once daily for 3 weeks. Response to treatment was evaluated using [18F] fluorodeoxyglucose positron emission tomography (PET) and computed tomography (CT) scans during treatment and histologic examination of the resection specimen. Primary end points were toxicity and pathologic response. Results Sixty patients were included. Seven patients stopped treatment prematurely (12%). Skin toxicity was present in 37 patients (62%), and diarrhea was present in 21 patients (35%). PET evaluation revealed metabolic response (&gt; 25% standardized uptake value decrease) in 16 patients (27%); CT evaluation using Response Evaluation Criteria in Solid Tumors (RECIST) showed response in three patients (5%). At surgery, no unexpected complications occurred. Pathologic examination showed more than 50% necrosis in 14 patients (23%), of whom three (5%) had more than 95% tumor necrosis. The response rate in the enriched population was 34% (10 of 29 patients). Conclusion According to predefined criteria, neoadjuvant erlotinib has low toxicity and sufficient activity to deserve further testing in future studies in an enriched population.
Hypoxic training and team sports: a challenge to traditional methods?
Authors: Grégoire P Millet, Raphaël Faiss, Franck Brocherie, Olivier Girard
Journal: British Journal of Sports Medicine (2013)

In 2007, Wilber1 presented the main altitude/hypoxic training methods used by elite athletes: ‘live high—train high’ (LHTH) and ‘live high—train low’ (LHTL); sleeping at altitude to gain the haematological adaptations (increased erythrocyte volume) but training at sea level to maximise performance (maintenance of sea-level training intensity and oxygen flux). The LHTL method can be accomplished through a number of methods and devices: natural/terrestrial altitude, nitrogen dilution, oxygen filtration and supplemental oxygen. Another method is the ‘live low—train high’ (LLTH) method including intermittent hypoxic exposure at rest (IHE) or during intermittent hypoxic training sessions (IHT). Noteworthy, all supporting references were conducted with endurance elite athletes (ie, cyclists, triathletes, cross-country skiers, runners, swimmers, kayakers and rowers) and there is an extensive literature relative to LHTH as well as LHTL. However, there is a lack of evidence for the applicability of these methods in team-sport athletes.

In recent times, media reports have provided us with coverage of some high-profile clubs or national squads in various team-sport disciplines undertaking fitness programmes at altitude during the early preseason or in preparation of a major competition. Despite the evident observation that athletes from different team sports and from all around the world are using altitude training more than ever before, it is …
Complement receptor 2–mediated targeting of complement inhibitors to sites of complement activation
Authors: Hongbin Song, Chun He, Christian Knaak, Joel M. Guthridge, V. Michael Holers, Stephen Tomlinson
Journal: Journal of Clinical Investigation (2003)

In a strategy to specifically target complement inhibitors to sites of complement activation and disease, recombinant fusion proteins consisting of a complement inhibitor linked to a C3 binding region of complement receptor (CR) 2 were prepared and characterized. Natural ligands for CR2 are C3 breakdown products deposited at sites of complement activation. Fusion proteins were prepared consisting of a human CR2 fragment linked to either the N terminus or C terminus of soluble forms of the membrane complement inhibitors decay accelerating factor (DAF) or CD59. The targeted complement inhibitors bound to C3-opsonized cells, and all were significantly more effective (up to 20-fold) than corresponding untargeted inhibitors at protecting target cells from complement. CR2 fusion proteins also inhibited CR3-dependent adhesion of U937 cells to C3 opsonized erythrocytes, indicating a second potential anti-inflammatory mechanism of CR2 fusion proteins, since CR3 is involved in endothelial adhesion and diapedesis of leukocytes at inflammatory sites. Finally, the in vivo validity of the targeting strategy was confirmed by the demonstration that CR2-DAF, but not soluble DAF, targets to the kidney in mouse models of lupus nephritis that are associated with renal complement deposition.
Sudden whitening of the hair: an historical fiction?
Authors: Anne-Marie Skellett, George WM Millington, Nick J Levell
Journal: Journal of the Royal Society of Medicine (2008)

Sudden hair whitening (canities) was first reported centuries ago. Although a rare event, it has affected well-known historical figures, including Sir Thomas Moore and Queen Marie Antoinette of France. Early reports are substantiated by more recent cases in the scientific literature. Often, there is association with psychological stress; in the two historical cases above, the condition is thought to have been a reaction to the sentence of execution. In this paper, we examine some case histories of those afflicted throughout history and discuss hypotheses to explain the phenomenon.
Bone density for prediction of hip fracture
Authors: Peter Schneider, Wilhelm Börner, StevenR. Cummings, DennisM. Black, MichaelC. Nevitt, Warren Browner, Jane Cauley, Kris Ensrud, HarryK. Genant, Lisa Palermo, Jean Scott, ThomasM. Vogt
Journal: The Lancet (1993)
The prodrug DHED selectively delivers 17β-estradiol to the brain for treating estrogen-responsive disorders
Authors: Laszlo Prokai, Vien Nguyen, Szabolcs Szarka, Puja Garg, Gauri Sabnis, Heather A. Bimonte-Nelson, Katie J. McLaughlin, Joshua S. Talboom, Cheryl D. Conrad, Paul J. Shughrue, Todd D. Gould, Angela Brodie, Istvan Merchenthaler, Peter Koulen, Katalin Prokai-Tatrai
Journal: Science Translational Medicine (2015)

Many neurological and psychiatric maladies originate from the deprivation of the human brain from estrogens. However, current hormone therapies cannot be used safely to treat these conditions commonly associated with menopause because of detrimental side effects in the periphery. The latter also prevents the use of the hormone for neuroprotection. We show that a small-molecule bioprecursor prodrug, 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), converts to 17β-estradiol in the brain after systemic administration but remains inert in the rest of the body. The localized and rapid formation of estrogen from the prodrug was revealed by a series of in vivo bioanalytical assays and through in vivo imaging in rodents. DHED treatment efficiently alleviated symptoms that originated from brain estrogen deficiency in animal models of surgical menopause and provided neuroprotection in a rat stroke model. Concomitantly, we determined that 17β-estradiol formed in the brain from DHED elicited changes in gene expression and neuronal morphology identical to those obtained after direct 17β-estradiol treatment. Together, complementary functional and mechanistic data show that our approach is highly relevant therapeutically, because administration of the prodrug selectively produces estrogen in the brain independently from the route of administration and treatment regimen. Therefore, peripheral responses associated with the use of systemic estrogens, such as stimulation of the uterus and estrogen-responsive tumor growth, were absent. Collectively, our brain-selective prodrug approach may safely provide estrogen neuroprotection and medicate neurological and psychiatric symptoms developing from estrogen deficiency, particularly those encountered after surgical menopause, without the adverse side effects of current hormone therapies.
Purification and physical-chemical characterization of hepatic stimulator substance
Authors: Douglas R. Labrecque, Gregory Steele, Steven Fogerty, Michelle Wilson, James Barton
Journal: Hepatology (1987)

Hepatic stimulator substance is a liver growth stimulator derived from the hepatocyte cytosol of weanling or regenerating adult rat livers. The present paper reports the almost 9,000-fold purification of hepatic stimulator substance with an approximately 100,000-fold increase in specific growth stimulator activity. Purification steps included heating at 95°C for 15 min, 40% cold ethanol precipitation, passage over Procion Red HE3B, DEAE cellulose and Sephadex G75 columns and gel filtration and reverse-phase fast protein liquid chromatography techniques. As little as 27 ng per ml of the purest material produced a 2-fold stimulation in the standard HTC cell activity assay. Further studies indicate that hepatic stimulator substance is a highly negatively charged protein and that disulfide bonds or a complex tertiary structure are not essential to its activity. Hepatic stimulator substance is stable over a wide range of pH's and temperatures. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis with silver stain revealed 1 major band at 12,400 daltons and 1 minor band at 17,500 daltons.
Influence of Human CD8 on Antigen Recognition by T-Cell Receptor–Transduced Cells
Authors: Gretchen E. Lyons, Tamson Moore, Natasha Brasic, Mingli Li, Jeffrey J. Roszkowski, Michael I. Nishimura
Journal: Cancer Research (2006)

Abstract The CD8 coreceptor on T cells has two functions. Namely, CD8 acts to stabilize the binding of the T-cell receptor (TCR) to the peptide-MHC complex while localizing p56lck (lck) to the TCR/CD3 complex to facilitate early signaling events. Although both functions may be critical for efficient activation of a CTL, little is known about how the structural versus signaling roles of CD8, together with the relative strength of the TCR, influences T-cell function. We have addressed these issues by introducing full-length and truncated versions of the CD8α and CD8β chains into CD8− Jurkat cell clones expressing cloned TCRs with known antigen specificity and relative affinities. Using a combination of antigen recognition and tetramer-binding assays, we find that the intracellular lck-binding domain of CD8 is critical for enhanced T-cell activation regardless of the relative strength of the TCR. In contrast, the extracellular domain of CD8 seems to be critical for TCRs with lower affinity but not those with higher affinity. Based on our results, we conclude that there are different requirements for CD8 to enhance T-cell function depending on the strength of its TCR. (Cancer Res 2006; 66(23): 11455-61)
THE INHIBITORY EFFECT OF ACRIDINE ON THE SPOROGONY OF A COCCIDIUM (EIMERIA STIEDÆ)
Authors: Paul A. Lewis
Journal: The Journal of Experimental Medicine (1924)

The development or ripening of the oocyst of the coccidium of the rabbit is prevented by acridine hydrochloride provided that the cysts are exposed to the action of the chemical before development has started. After sporoblasts are formed acridine does not prevent further development. Many other substances, some of them known to be active against certain protozoan parasites, have no influence on the ripening of the oocysts of the coccidium.
Impaired Autoregulation of Blood Flow and Glomerular Filtration Rate in the Isolated Dog Kidney Depleted of Renin
Authors: GEORGE J. KALOYANIDES, ROBERT D. BASTRON, GERALD F. DIBONA
Journal: Circulation Research (1974)

The effect of renin depletion on autoregulation of renal blood flow and glomerular filtration rate was examined in an isolated perfused kidney preparation. Group 1 dogs received a normal-sodium diet, group 2 dogs received deoxycorticosterone acetate (DOCA) and a high-sodium diet, group 3 dogs received DOCA and a sodium-deficient diet, group 4 dogs received a high-sodium diet without DOCA, and dogs in groups 5 and 6 were treated just like dogs in groups 1 and 2, respectively. Renin release was stimulated by decreasing renal arterial pressure to 50 mm Hg. An increase in renal arterial pressure from 100 to 160 mm Hg was associated with an impaired autoregulatory response in kidneys from group 2 dogs and in two kidneys from group 4 dogs; these kidneys exhibited suppressed or absent renin release in response to a decrease in renal arterial pressure. A separate group of experiments demonstrated that DOCA plus a high-sodium diet completely depleted the kidney of renin stores, indicating that decreased renin secretion reflected depletion of renal renin content. Infusing angiotensin II (0.22 ± 0.06 µg/min) into the renal artery of group 2 kidneys did not normalize the autoregulatory response. A decrease in renal arterial pressure from 150 to 50 mm Hg was associated with impaired autoregulation of glomerular filtration rate and renal blood flow in kidneys from group 6 dogs; renin secretion was undetectable in these kidneys. All kidneys from groups 1, 3, and 5 and the remaining six kidneys from group 4 exhibited a normal autoregulatory response and normal renin release. In groups 1-3, zonal blood flow was measured using the radiolabeled microsphere technique. Only in group 2 did a significant redistribution of fractional blood flow from the inner to the outer cortex occur. These experiments demonstrate that renin depletion impairs the capacity of the kidney to autoregulate blood flow and glomerular filtration rate; thus the data are consistent with the hypothesis that the renin-angiotensin system participates in the autoregulatory response.
Ovarian tissue cryopreservation and transplantation: a review
Authors: Jacques Donnez, Belen Martinez-Madrid, Pascale Jadoul, Anne Van Langendonckt, Dominique Demylle, Marie-Madeleine Dolmans
Journal: Human Reproduction Update (2006)

The review covers current options for ovarian tissue cryopreservation and transplantation and provides a systematic review of the existing literature from the last 10 years, taking into account all previously published reviews on the subject. The different cryopreservation options available for fertility preservation in cancer patients are embryo cryopreservation, oocyte cryopreservation and ovarian tissue cryopreservation. The choice depends on various parameters: the type and timing of chemotherapy, the type of cancer, the patient's age and the partner status. The different options and their results are discussed, as well as their putative indications and efficacy. The review concludes that advances in reproductive technology have made fertility preservation techniques a real possibility for patients whose gonadal function is threatened by premature menopause, or by treatments such as radiotherapy, chemotherapy or surgical castration.
Anti-carbamylated protein (anti-CarP) antibodies precede the onset of rheumatoid arthritis
Authors: Jing Shi, Lotte A van de Stadt, E W Nivine Levarht, Tom W J Huizinga, Dörte Hamann, Dirkjan van Schaardenburg, René E M Toes, Leendert A Trouw
Journal: Annals of the Rheumatic Diseases (2013)

The presence of anti-citrullinated protein antibodies (ACPA) and IgM-rheumatoid factor (IgM-RF) years before the clinical diagnosis of rheumatoid arthritis (RA) suggests they are possibly involved in the pathogenic process underlying RA. In this study, we analysed whether anti-carbamylated protein (anti-CarP) antibodies, a novel autoantibody system against carbamylated proteins, can also be detected in healthy individuals before they developed RA.Multiple sera from asymptomatic blood donors prior to the onset of their RA symptoms and sera from age-matched and sex-matched controls were tested for the presence of antibodies directed against carbamylated-fetal calf serum (Ca-FCS), carbamylated-fibrinogen (Ca-Fib), cyclic citrullinated-peptide 2 and IgM-RF.Anti-Ca-FCS and anti-Ca-Fib antibodies were each present in 27% and 38% of the last serum samples of blood donors prior to the diagnosis of RA. Both anti-Ca-FCS and anti-Ca-Fib antibodies could be detected many years before the onset of RA. Anti-CarP antibodies as well as ACPA are, on average, detected earlier than IgM-RF.In addition to ACPA and IgM-RF, also the newly identified anti-CarP antibodies appear many years before the diagnosis of RA.