tbuckley/cabot-search huggingface dataset:
Serum levels of BAFF, but not APRIL, are increased after rituximab treatment in patients with primary Sjögren's syndrome: data from a placebo-controlled clinical trial
Authors: Rodney P E Pollard, Wayel H Abdulahad, Arjan Vissink, Nishath Hamza, Johannes G M Burgerhof, Jiska M Meijer, Annie Visser, Minke G Huitema, Fred K L Spijkervet, Cees G M Kallenberg, Hendrika Bootsma, Frans G M Kroese
Journal: Annals of the Rheumatic Diseases (2012)

B cell depletion therapy with rituximab (RTX; 2 weekly infusions of 1000 mg, premedication: 100 mg prednisolone) in primary Sjogren's syndrome (pSS) patients is effective in reducing subjective and objective symptoms.1 As B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are important cytokines involved in B cell survival and activation, we assessed in pSS patients included in a double-blind, randomised, placebo-controlled trial1 the effects of RTX on serum BAFF and APRIL levels up to 48 weeks after RTX.

Serum concentrations of BAFF and APRIL were measured by ELISA using kits from RD median 1277 pg/ml (range 907–3802 pg/ml)) compared with healthy controls (n=10; median 983 pg/ml (range 600–1564 pg/ml)); p<0.01; figure 1A). Also, baseline serum APRIL levels were significantly higher in pSS patients (median 15 098 pg/ml (range 1891–228 591 pg/ml)) than in healthy controls (median 1965 pg/ml (range 889–4567 pg/ml); p<0.05; …
Aberrant Regulation of Planar Cell Polarity in Polycystic Kidney Disease
Authors: Annouck Luyten, Xuefeng Su, Sarah Gondela, Ying Chen, Santiago Rompani, Ayumi Takakura, Jing Zhou
Journal: Journal of the American Society of Nephrology (2010)

Mutations in PKD1, which encodes polycystin-1 (PC1), contribute to >85% of cases of autosomal dominant polycystic kidney disease (ADPKD). The planar cell polarity (PCP) pathway is necessary for the oriented cell division and convergent extension that establishes and maintains the structure of kidney tubules, but the role of this pathway in the pathophysiology of ADPKD is incompletely understood. Here, we show that inactivation of Pkd1 in postnatal developing mouse kidneys leads to a defect in oriented cell division in precystic kidney tubules. We also observed this defect in precystic Pkd1-inactivated mature kidneys subjected to ischemia-reperfusion injury as a “third hit.” Cystic kidneys exhibited striking upregulation and activation of Frizzled 3 (Fz3), a regulator of PCP, and its downstream effector, CDC42. Precystic kidneys demonstrated upregulation of CDC42, but the localization of the polarity proteins Par3 and Par6 was similar to control. Fz3 was expressed on the cilia of cystic kidneys but barely detected on the cilia of normal kidneys. In vitro, PC1 and Fz3 antagonized each other to control CDC42 expression and the rate of cell migration in HEK293T cells. Taken together, our data suggest that PC1 controls oriented cell division and that aberrant PCP signaling contributes to cystogenesis.
PREVACCINATED SMALL-POX
Authors: J. D. Howe
Journal: BMJ (1903)

Morbid Anatomy. (a) Vessels.-Thedigital arteries of the fingers showed very slight thickening, those of the thumb showed obvious thickening in the internal coat.The ulnar artery showed some thickening of the internal coat but the radial artery showed much more pronounced changes.(b) Nerves.-There was no definite sign of recent degeneration in any of the nerves, nor was there an apparent deficiency of nerve fibres or in- crease of fibrous tissue in the larger nerve trunks or in the digital nerves.
Evaluation of Lapatinib and Topotecan Combination Therapy: Tissue Culture, Murine Xenograft, and Phase I Clinical Trial Data
Authors: Julian R. Molina, Scott H. Kaufmann, Joel M. Reid, Stephen D. Rubin, Marina Gálvez-Peralta, Robert Friedman, Karen S. Flatten, Kevin M. Koch, Tona M. Gilmer, Robert J. Mullin, Roxanne C. Jewell, Sara J. Felten, Sumithra Mandrekar, Alex A. Adjei, Charles Erlichman
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Topotecan resistance can result from drug efflux by P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) as well as survival signals initiated by epidermal growth factor receptor family members. The present studies were done to determine the effect of combining topotecan and the dual epidermal growth factor receptor/HER2 inhibitor lapatinib in tissue culture, a murine xenograft model, and a phase I clinical trial. Experimental Design: The effects of lapatinib on topotecan accumulation and cytotoxicity in vitro were examined in paired cell lines lacking or expressing Pgp or BCRP. Antiproliferative effects of the combination were assessed in mice bearing HER2+ BT474 breast cancer xenografts. Based on tolerability in this preclinical model, 37 patients with advanced-stage cancers received escalating doses of lapatinib and topotecan in a phase I trial. Results: Lapatinib increased topotecan accumulation in BCRP- or Pgp-expressing cells in vitro, and the combination showed enhanced efficacy in HER2+ BT474 xenografts. In the phase I study, nausea, vomiting, diarrhea, and fatigue were dose limiting. The maximum tolerated doses were 1,250 mg/d lapatinib by mouth for 21 or 28 days with 3.2 mg/m2 topotecan i.v. on days 1, 8, and 15 of 28-day cycles. Pharmacokinetic analyses showed that combined drug administration resulted in decreased topotecan clearance consistent with transporter-mediated interactions. Seventeen (46%) patients had disease stabilization. Conclusions: The lapatinib/topotecan combination is well tolerated and warrants further study.
Hypertrophic gastropathy resembling Ménétrier's disease in transgenic mice overexpressing transforming growth factor alpha in the stomach.
Authors: H Takagi, C Jhappan, R Sharp, G Merlino
Journal: Journal of Clinical Investigation (1992)

Transforming growth factor alpha (TGF alpha) is thought to participate in the normal and pathologic processes of numerous tissues, including the gastric mucosa. To explore its role in vivo, transgenic mice were generated overexpressing TGF alpha in the stomach. TGF alpha induced dramatic structural and functional lesions of the glandular stomach that were similar to Ménétrier's disease in humans. Transgenic mice developed severe adenomatous hyperplasia that resulted in a striking nodular thickening or hypertrophy of the gastric mucosa. Secretions obtained from affected stomachs contained no detectable gastric acid, suggesting that parietal cell function had been greatly impaired. These findings demonstrate that overproduction of TGF alpha can stimulate cellular proliferation, suppress acid secretion, and perturb organogenesis of the stomach of transgenic mice. Moreover, TGF alpha may contribute to the pathogenesis of related human hypertrophic gastropathies, such as Ménétrier's disease.
Home Use of Automated External Defibrillators for Sudden Cardiac Arrest
Authors: Gust H. Bardy, Kerry L. Lee, Daniel B. Mark, Jeanne E. Poole, William D. Toff, Andrew M. Tonkin, Warren Smith, Paul Dorian, Douglas L. Packer, Roger D. White, W.T. Longstreth, Jill Anderson, George Johnson, Eric Bischoff, Julie J. Yallop, Steven McNulty, Linda Davidson Ray, Nancy E. Clapp-Channing, Yves Rosenberg, Eleanor B. Schron
Journal: New England Journal of Medicine (2008)

The most common location of out-of-hospital sudden cardiac arrest is the home, a situation in which emergency medical services are challenged to provide timely care. Consequently, home use of an automated external defibrillator (AED) might offer an opportunity to improve survival for patients at risk.
Expression of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Receptors 1 and 2 in Melanoma
Authors: Mary M. McCarthy, Kyle A. DiVito, Mario Sznol, Daniela Kovacs, Ruth Halaban, Aaron J. Berger, Keith T. Flaherty, Robert L. Camp, Rossitza Lazova, David L. Rimm, Harriet M. Kluger
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The proapoptotic receptors tumor necrosis factor–related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and TRAIL-R2 are targets of drugs in clinical development, and receptor expression levels may be important determinants of sensitivity to receptor agonists. We assessed TRAIL-R1 and TRAIL-R2 expression patterns in a large cohort of melanomas and benign nevi. Experimental Design: We analyzed tissue microarrays containing 546 melanomas and 540 nevi using our automated quantitative method to measure protein levels in situ (AQUA). The system uses S100 to define pixels as melanoma (tumor mask) within the array spot and measures intensity of TRAIL-receptor expression using Cy5-conjugated antibodies within the mask. AQUA scores were correlated with clinical and pathologic variables. Results: TRAIL-R1 and TRAIL-R2 expression was higher in melanomas than in nevi (P &amp;lt; 0.0001), and higher in primary than in metastatic specimens (P = 0.0031 and P &amp;lt; 0.0001, respectively). TRAIL-R1 and TRAIL-R2 expression exceeding the 95th percentile for nevi was found in 19% and 74% of melanoma specimens, respectively. Although on univariate analysis, high TRAIL-R2 expression correlated with increased survival (P = 0.0439), it was not associated with survival within the primary or metastatic subcohorts. TRAIL-R1 expression was not associated with survival. Conclusions: TRAIL-R1 and TRAIL-R2 expression is higher in malignant melanocytes than in their benign counterparts, suggesting that these receptors might be effective therapeutic targets in melanoma. Expression is higher in early-stage disease than in metastatic specimens, and expression exceeding that found in nevi is found in a substantially larger fraction of melanomas for TRAIL-R2 compared with TRAIL-R1. Assessment of baseline tumor TRAIL receptor expression may be important in analysis of clinical trials involving TRAIL receptor agonists.
Mycoplasma pneumonia with fulminant evolution into diffuse interstitial fibrosis.
Authors: J M Kaufman, C A Cuvelier, M Van der Straeten
Journal: Thorax (1980)

A fatal case of interstitial pneumonia caused by Mycoplasma pneumoniae with fulminant evolution into diffuse interstitial fibrosis is reported. Treatment with tetracycline and corticosteroids failed to arrest the progress of the disease. Fatal Mycoplasma pneumoniae infections have been reported previously and some degree of pulmonary fibrosis has been described in a few cases but as far as could be ascertained there are no other well-documented cases of diffuse interstitial fibrosis with proved Mycoplasma pneumoniae infection.
Correlation Between Serum 25-Hydroxyvitamin D Concentration and Methicillin - Resistant Staphylococcus Aureus Skin Infection in Atopic Dermatitis
Authors: Taek Ki Min, You Hoon Jeon, Hyeon Jong Yang, Hae Won Lee, Bok Yang Pyun
Journal: Journal of Allergy and Clinical Immunology (2013)
Humoral regulation of blood flow to choroid plexus: role of arginine vasopressin.
Authors: F M Faraci, W G Mayhan, W J Farrell, D D Heistad
Journal: Circulation Research (1988)

The goal of this study was to examine humoral mechanisms that regulate blood flow to the choroid plexus. We determined the effects of arginine vasopressin on blood flow (microspheres) to the choroid plexus in anesthetized and awake rabbits. In anesthetized rabbits, blood flow to the choroid plexus was 342 +/- 31 (mean +/- SEM) ml/min/100 g under control conditions. Intravenous infusion of vasopressin at 4 and 40 mU/kg increased plasma vasopressin levels from 11 +/- 1 to 55 +/- 15 and 441 +/- 120 pg/ml, respectively, and blood flow to the choroid plexus decreased by 48 +/- 6% and 70 +/- 4%. Cerebral blood flow was not affected by infusion of vasopressin. Similar responses to infusion of vasopressin were observed in awake rabbits. The V1 antagonist [d(CH2)5Tyr(Me)AVP] (10 micrograms/kg i.v.) had no effect on resting blood flow, but abolished the effect of vasopressin on blood flow to the choroid plexus. Vasoconstrictor responses of the choroid plexus to intravenous infusion of phenylephrine were not attenuated by the V1 antagonist. Thus, circulating vasopressin, at plasma levels that are observed under physiological and pathophysiological conditions, has marked effects on blood flow to the choroid plexus. These effects appear to be mediated through a V1 receptor. We speculate that vasopressin may play an important role in regulation of blood flow to the choroid plexus and perhaps in the regulation of cerebrospinal fluid production.
Presence of FoxP3+ Regulatory T Cells Predicts Outcome of Subclinical Rejection of Renal Allografts
Authors: Oriol Bestard, Josep M. Cruzado, Ine[Combining Acute Accent]s Rama, Joan Torras, Montse Goma[Combining Grave Accent], Daniel Sero[Combining Acute Accent]n, Francesc Moreso, Salvador Gil-Vernet, Josep M. Grinyo[Combining Acute Accent]
Journal: Journal of the American Society of Nephrology (2008)

Subclinical rejection (SCR) of renal allografts refers to histologic patterns of acute rejection despite stable renal function. The clinical approach to SCR is controversial; it would be helpful to identify biomarkers that could determine whether the identified cellular infiltrates were detrimental. For investigation of whether the presence of FoxP3+ regulatory T cells (Treg) could help determine the functional importance of tubulointerstitial infiltrates observed in 6-mo protocol biopsies, 37 cases of SCR were evaluated. The presence of FoxP3+ Treg discriminated harmless from injurious infiltrates, evidenced by independently predicting better graft function 2 and 3 yr after transplantation. Furthermore, the FoxP3+ Treg/CD3+ T cell ratio positively correlated with graft function at 2 yr after transplantation, suggesting that an increasing proportion of Treg within the global T cell infiltrate may facilitate renal engraftment; therefore, immunostaining for FoxP3+ Treg in patients with SCR on protocol biopsies may ultimately be useful to identify patients who may require alterations in their immunosuppressive regimens.
Decade-Long Safety and Function of Retroviral-Modified Chimeric Antigen Receptor T Cells
Authors: John Scholler, Troy L. Brady, Gwendolyn Binder-Scholl, Wei-Ting Hwang, Gabriela Plesa, Kristen M. Hege, Ashley N. Vogel, Michael Kalos, James L. Riley, Steven G. Deeks, Ronald T. Mitsuyasu, Wendy B. Bernstein, Naomi E. Aronson, Bruce L. Levine, Frederic D. Bushman, Carl H. June
Journal: Science Translational Medicine (2012)

Adoptively transferred chimeric antigen receptor T cells have stable stem cell–like persistence for at least a decade and more than 500 years of patient safety.
Physicians, Clergymen and the Privileged Communication
Authors: Rev William J. Fogleman
Journal: JAMA (1967)

The minister in our church is also a close personal friend. He has on a number of occasions suggested that I, as a physician, should be aware of the fact that there are some discrepancies in the current attitudes of physicians toward communication with clergymen. It is his opinion that he has frequently been unable to be of maximum service to his parishioners because of the medical profession's lack of understanding of the role of the clergyman in counseling and supporting the ill. What is your frank opinion of the intent as well as the implementation of the concept of privileged communication between physicians and physician and clergyman? Do you believe that physicians are inclined to assume functions which more properly belong in the realm of the ministry?
Cancer Research Campaign health education programme to promote the early detection of cutaneous malignant melanoma. II. Characteristics and incidence of melanoma
Authors: J. MELIA, E.J. COOPER, T. FROST, R. GRAHAM-BROWN, J. HUNTER, A. MARSDEN, A. VIVIER, J. WHITE, S. WHITEHEAD, A.P. WARIN, M. WROUGHTON, R. ELLMAN, J. CHAMBERLAIN
Journal: British Journal of Dermatology (1995)

Journal Article Cancer Research Campaign health education programme to promote the early detection of cutaneous malignant melanoma. II. Characteristics and incidence of melanoma Get access J. MELIA, J. MELIA Cancer Screening Evaluation Unit, Institute of Cancer Research. Section of Epidemiology, D Block, Cotswold Road. Sutton, Surrey, SM2 5NG, U.K. Search for other works by this author on: Oxford Academic Google Scholar E.J. COOPER, E.J. COOPER The Royal Infirmary. Edinburgh. U.K. Search for other works by this author on: Oxford Academic Google Scholar T. FROST, T. FROST Royal Devon & Exeter Hospital, Exeter. U.K. Search for other works by this author on: Oxford Academic Google Scholar R. GRAHAM‐BROWN, R. GRAHAM‐BROWN Leicester Royal Infirmary. Leicester, U.K. Search for other works by this author on: Oxford Academic Google Scholar J. HUNTER, J. HUNTER Royal Devon & Exeter Hospital, Exeter. U.K. Search for other works by this author on: Oxford Academic Google Scholar A. MARSDEN, A. MARSDEN St George's Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar A. DU VIVIER, A. DU VIVIER King's College Hospital, London, U. K. Search for other works by this author on: Oxford Academic Google Scholar J. WHITE, J. WHITE Royal South Hants Hospital. Southampton U.K. Search for other works by this author on: Oxford Academic Google Scholar S. WHITEHEAD, S. WHITEHEAD Southern Derbyshire Health Authority, Derby. U.K. Search for other works by this author on: Oxford Academic Google Scholar A.P. WARIN, A.P. WARIN Royal Devon & Exeter Hospital, Exeter. U.K. Search for other works by this author on: Oxford Academic Google Scholar ... Show more M. WROUGHTON, M. WROUGHTON c/oQueen's Medical Centre, Nottingham, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. ELLMAN, R. ELLMAN Cancer Screening Evaluation Unit, Institute of Cancer Research. Section of Epidemiology, D Block, Cotswold Road. Sutton, Surrey, SM2 5NG, U.K. Search for other works by this author on: Oxford Academic Google Scholar J. CHAMBERLAIN J. CHAMBERLAIN Cancer Screening Evaluation Unit, Institute of Cancer Research. Section of Epidemiology, D Block, Cotswold Road. Sutton, Surrey, SM2 5NG, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 132, Issue 3, 1 March 1995, Pages 414–421, https://doi.org/10.1111/j.1365-2133.1995.tb08675.x Published: 01 March 1995 Article history Accepted: 07 June 1994 Published: 01 March 1995
The emergence of influenza A H7N9 in human beings 16 years after influenza A H5N1: a tale of two cities
Authors: Kelvin KW To, Jasper FW Chan, Honglin Chen, Lanjuan Li, Kwok-Yung Yuen
Journal: The Lancet Infectious Diseases (2013)

Infection with either influenza A H5N1 virus in 1997 or avian influenza A H7N9 virus in 2013 caused severe pneumonia that did not respond to typical or atypical antimicrobial treatment, and resulted in high mortality. Both viruses are reassortants with internal genes derived from avian influenza A H9N2 viruses that circulate in Asian poultry. Both viruses have genetic markers of mammalian adaptation in their haemagglutinin and polymerase PB2 subunits, which enhanced binding to human-type receptors and improved replication in mammals, respectively. Hong Kong (affected by H5N1 in 1997) and Shanghai (affected by H7N9 in 2013) are two rapidly flourishing cosmopolitan megacities that were increasing in human population and poultry consumption before the outbreaks. Both cities are located along the avian migratory route at the Pearl River delta and Yangtze River delta. Whether the widespread use of the H5N1 vaccine in east Asia-with suboptimum biosecurity measures in live poultry markets and farms-predisposed to the emergence of H7N9 or other virus subtypes needs further investigation. Why H7N9 seems to be more readily transmitted from poultry to people than H5N1 is still unclear.
More than skin deep: connecting melanocyte pigmentation and angiogenic diseases
Authors: Christopher D. Kontos
Journal: Journal of Clinical Investigation (2013)

Epidemiological studies have identified racial differences in susceptibility to numerous diseases, including several ocular and skin diseases characterized by increased vascular growth. In most cases, the specific mechanisms and genetic variants responsible for these differences have remained elusive. In this issue of the JCI, Adini et al. explore a direct connection between skin pigmentation and susceptibility to angiogenic diseases and identify an extracellular matrix protein that is regulated by melanogenesis and potently modulates angiogenesis.
Increased enzymatic activity of the alternative pathway convertase when bound to the erythrocytes of paroxysmal nocturnal hemoglobinuria.
Authors: C J Parker, P J Baker, W F Rosse
Journal: Journal of Clinical Investigation (1982)

To investigate the greater fixation of C3 to the erythrocytes of patients with paroxysmal nocturnal hemoglobinuria (PNH) upon activation of complement, we have examined the formation and the reaction of the C3 nephritic factor-stabilized alternative pathway convertase made with purified components on normal and PNH erythrocytes. Each convertase complex converts four to five times more fluid-phase C3 to C3b when affixed to a PNH cell than when affixed to a normal cell. The greater activity of the convertase on PNH cells is not due to differences in the intrinsic or extrinsic stability of the convertase complex. The excessive binding of C3 to PNH cell si due to this increased conversion of fluid-phase C3, because the efficiency of binding of nascent C3b was identical for the two cell types. This is the first instance in which the enzyme activity of a complement complex has been shown to be increased by being affixed to an abnormal surface.
Vitamin D, Calcium Supplementation, and Colorectal Adenomas: Results of a Randomized Trial
Authors: M. V. Grau
Journal: JNCI Journal of the National Cancer Institute (2003)

Calcium and vitamin D both appear to have antineoplastic effects in the large bowel. Although these nutrients are inter-related metabolically in bone and in the normal intestine, their potential interactions in large-bowel carcinogenesis are not well understood.We assessed independent and joint effects of calcium supplementation and vitamin D status on adenoma recurrence in 803 subjects in a multi-center, placebo-controlled randomized clinical trial of calcium supplementation for the prevention of colorectal adenoma recurrence. Serum levels of 25-hydroxy [25-(OH)] vitamin D and 1,25-dihydroxy [1,25-(OH)2] vitamin D levels were determined, and the Taq I and Fok I polymorphisms in the vitamin D receptor (VDR) gene were analyzed by polymerase chain reaction. Risk ratios (RRs) for any adenoma recurrence were computed for calcium supplementation within groups defined by serum vitamin D levels and for serum vitamin D levels within treatment groups. Associations of VDR polymorphisms with recurrence risk were also evaluated. All statistical tests were two-sided.Among subjects with baseline 25-(OH) vitamin D levels at or below the median (29.1 ng/mL), calcium supplementation was not associated with adenoma recurrence, whereas among those with levels above the median, calcium supplementation was associated with a reduced risk (RR = 0.71, 95 % confidence interval [CI] = 0.57 to 0.89, P for interaction =.012). Conversely, serum 25-(OH) vitamin D levels were associated with a reduced risk only among subjects receiving calcium supplements (RR per 12 ng/mL increase of vitamin D = 0.88, 95% CI = 0.77 to 0.99, P for interaction =.006). VDR polymorphisms were not related to adenoma recurrence and did not modify the associations with vitamin D or calcium.Calcium supplementation and vitamin D status appear to act largely together, not separately, to reduce the risk of colorectal adenoma recurrence. VDR genotype does not appear to be associated with risk.