tbuckley/cabot-search huggingface dataset:
<i>In vitro</i> Biological Characterization of a Novel, Synthetic Diaryl Pyrazole Resorcinol Class of Heat Shock Protein 90 Inhibitors
Authors: Swee Y. Sharp, Kathy Boxall, Martin Rowlands, Chrisostomos Prodromou, S. Mark Roe, Alison Maloney, Marissa Powers, Paul A. Clarke, Gary Box, Sharon Sanderson, Lisa Patterson, Thomas P. Matthews, Kwai-Ming J. Cheung, Karen Ball, Angela Hayes, Florence Raynaud, Richard Marais, Laurence Pearl, Sue Eccles, Wynne Aherne, Edward McDonald, Paul Workman
Journal: Cancer Research (2007)

Abstract The molecular chaperone heat shock protein 90 (HSP90) has emerged as an exciting molecular target. Derivatives of the natural product geldanamycin, such as 17-allylamino-17-demethoxy-geldanamycin (17-AAG), were the first HSP90 ATPase inhibitors to enter clinical trial. Synthetic small-molecule HSP90 inhibitors have potential advantages. Here, we describe the biological properties of the lead compound of a new class of 3,4-diaryl pyrazole resorcinol HSP90 inhibitor (CCT018159), which we identified by high-throughput screening. CCT018159 inhibited human HSP90β with comparable potency to 17-AAG and with similar ATP-competitive kinetics. X-ray crystallographic structures of the NH2-terminal domain of yeast Hsp90 complexed with CCT018159 or its analogues showed binding properties similar to radicicol. The mean cellular GI50 value of CCT018159 across a panel of human cancer cell lines, including melanoma, was 5.3 μmol/L. Unlike 17-AAG, the in vitro antitumor activity of the pyrazole resorcinol analogues is independent of NQO1/DT-diaphorase and P-glycoprotein expression. The molecular signature of HSP90 inhibition, comprising increased expression of HSP72 protein and depletion of ERBB2, CDK4, C-RAF, and mutant B-RAF, was shown by Western blotting and quantified by time-resolved fluorescent-Cellisa in human cancer cell lines treated with CCT018159. CCT018159 caused cell cytostasis associated with a G1 arrest and induced apoptosis. CCT018159 also inhibited key endothelial and tumor cell functions implicated in invasion and angiogenesis. Overall, we have shown that diaryl pyrazole resorcinols exhibited similar cellular properties to 17-AAG with potential advantages (e.g., aqueous solubility, independence from NQO1 and P-glycoprotein). These compounds form the basis for further structure-based optimization to identify more potent inhibitors suitable for clinical development. [Cancer Res 2007;67(5):2206–16]
Identification of Borrelia burgdorferi in Diffuse Fasciitis With Peripheral Eosinophilia: Borrelial Fasciitis
Authors: S R Granter, R L Barnhill, M E Hewins, P H Duray
Journal: JAMA (1994)

To determine if spirochetes could be localized in biopsy specimens of patients with diffuse fasciitis and peripheral eosinophilia.Tissue from two patients received in consultation and retrieved from hospital files. One patient had a history of tick bite and erythema migrans.Tertiary care center and pathology consultation practice.Multiple tissue sections were examined for spirochetes using the modified Dieterle or Steiner technique. One case was examined using rabbit polyclonal antibodies against Borrelia burgdorferi. One case had sufficient tissue to study for B burgdorferi DNA by polymerase chain reaction.We identified two cases of diffuse fasciitis associated with peripheral eosinophilia in which spirochetal organisms were identified. The two patients had positive or borderline B burgdorferi serological findings. Deep biopsy was diagnostic of diffuse fasciitis with eosinophilia. In one patient, multiple organisms were seen using a modified Dieterle silver stain, and B burgdorferi-specific DNA was amplified by polymerase chain reaction. In the other patient, no unequivocal organisms were detected on silver stain; however, organisms were detected using rabbit polyclonal antibodies against B burgdorferi.Some cases of what has previously been described as "eosinophilic" fasciitis may be an expression of Lyme disease, and we propose the more specific term borrelial fasciitis to describe such lesions.
Randomised controlled trial of effect of leaflets to empower patients in consultations in primary care
Authors: Paul Little, Martina Dorward, Greg Warner, Michael Moore, Katharine Stephens, Jane Senior, Tony Kendrick
Journal: BMJ (2004)

To assess the impact of leaflets encouraging patients to raise concerns and to discuss symptoms or other health related issues in the consultation.Randomised controlled trial.Five general practices in three settings in the United Kingdom.636 consecutive patients, aged 16-80 years, randomised to receive a general leaflet, a depression leaflet, both, or neither.Mean item score on the medical interview satisfaction scale, consultation time, prescribing, referral, and investigation.The general leaflet increased patient satisfaction and was more effective with shorter consultations (leaflet 0.64, 95% confidence interval 0.19 to 1.08; time 0.31, 0.0 to 0.06; interaction between both -0.045, -0.08 to-0.009), with similar results for subscales related to the different aspects of communication. Thus for a 10 minute consultation the leaflet increased satisfaction by 7% (seven centile points) and for a five minute consultation by 14%. The leaflet overall caused a small non-significant increase in consultation time (0.36 minutes, -0.54 to 1.26). Although there was no change in prescribing or referral, a general leaflet increased the numbers of investigations (odds ratio 1.43, 1.00 to 2.05), which persisted when controlling for the major potential confounders of perceived medical need and patient preference (1.87, 1.10 to 3.19). Most of excess investigations were not thought strongly needed by the doctor or the patient. The depression leaflet had no significant effect on any outcome.Encouraging patients to raise issues and to discuss symptoms and other health related issues in the consultation improves their satisfaction and perceptions of communication, particularly in short consultations. Doctors do, however, need to elicit expectations to prevent needless investigations.
The significance of bcr-abl molecular detection in chronic myeloid leukemia patients “late,” 18 months or more after transplantation
Authors: Jerald P. Radich, Ted Gooley, Eileen Bryant, Tom Chauncey, Reginald Clift, Lan Beppu, Scott Edmands, Mary E. D. Flowers, Keith Kerkof, Ross Nelson, Frederick R. Appelbaum
Journal: Blood (2001)
A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses
Authors: Koichiro Takahashi, Takuma Shibata, Sachiko Akashi-Takamura, Takashi Kiyokawa, Yasutaka Wakabayashi, Natsuko Tanimura, Toshihiko Kobayashi, Fumi Matsumoto, Ryutaro Fukui, Taku Kouro, Yoshinori Nagai, Kiyoshi Takatsu, Shin-ichiroh Saitoh, Kensuke Miyake
Journal: The Journal of Experimental Medicine (2007)

Immune cells express multiple Toll-like receptors (TLRs) that are concomitantly activated by a variety of pathogen products. Although there is presumably a need to coordinate the expression and function of TLRs in individual cells, little is known about the mechanisms governing this process. We show that a protein associated with TLR4 (PRAT4A) is required for multiple TLR responses. PRAT4A resides in the endoplasmic reticulum, and PRAT4A knockdown inhibited trafficking of TLR1 and TLR4 to the cell surface and ligand-induced trafficking of TLR9 to lysosomes. Other cell-surface molecules were expressed normally on immunocytes from PRAT4A−/− mice. There was impaired cytokine production to TLR ligands, except to the TLR3 ligand poly(I:C), and to whole bacteria. Activation of antigen-specific T helper type 1 responses were also defective. Moreover, PRAT4A−/− bone marrow chimeric mice were resistant to lipopolysaccharide-induced sepsis. These results suggest that PRAT4A regulates the subcellular distribution and response of multiple TLRs and is required for both innate and adaptive immune responses.
Itraconazole, a new orally active antifungal, in the treatment of pityriasis versicolor
Authors: J. DELESCLUSE, G. CAUWENBERGH, H. DEGREEF
Journal: British Journal of Dermatology (1986)

Itraconazole, a new orally active triazole antifungal, has been tested in patients with pityriasis versicolor. A comparison of different dose schedules was carried out in 73 patients. A regime of 100 mg itraconazole daily for 15 days gave a 100% response rate; 200 mg daily for 5 days gave an 80% response rate. Two patients, who had received 50 mg itraconazole for 14 days, relapsed within 2 months of finishing treatment. Only two patients reported minor side-effects.
Pleural drainage and pleurodesis: implementation of guidelines in four hospitals
Authors: J. A. Burgers, P. W. A. Kunst, M. G. J. Koolen, L. N. A. Willems, J. S. Burgers, M. van den Heuvel
Journal: European Respiratory Journal (2008)

The aim of the present study was to evaluate the implementation of the 2003 Dutch guideline on the diagnosis and treatment of malignant pleural effusions, and the potential effect of the implementation on the clinical outcome of pleurodesis. All patients with malignant pleural effusion who had a pleural drain placed with the intention of performing pleurodesis were registered prospectively in four centres. Details of the procedure and fluid recurrence and survival data were noted. Patients with a proven malignancy (n = 100) were entered into the registration database. Diagnostic guideline recommendations were followed in 60-70% of the patients. Surprisingly, pleurodesis was performed in only 75% of the patients, mainly due to the presence of a trapped lung. All pleurodeses were performed using talc, according to the guideline. Follow-up revealed fluid recurrence in 27 (36%) patients after a mean follow-up of 17 days (range 2-285 days); 14 patients with successful pleurodesis died with a median survival of 61 days (range 13-174 days). Systemic treatment following pleurodesis and good apposition of the pleural surfaces during drainage were good prognostic factors. Despite reasonable-to-good adherence to the guideline, the number of successful pleurodeses was low. Better predictors of a good pleurodesis outcome are needed.
Percent Change in Wound Area of Diabetic Foot Ulcers Over a 4-Week Period Is a Robust Predictor of Complete Healing in a 12-Week Prospective Trial
Authors: Peter Sheehan, Peter Jones, Antonella Caselli, John M. Giurini, Aristidis Veves
Journal: Diabetes Care (2003)

OBJECTIVE—To assess the ability of the 4-week healing rate to predict complete healing over a 12-week period in a large prospective multicenter trial of diabetic patients with foot ulceration. RESEARCH DESIGN AND METHODS—We examined the change in ulcer area over a 4-week period as a predictor of wound healing within 12 weeks in patients who were seen weekly in a prospective, randomized controlled trial. RESULTS—Wound area measurements at baseline and after 4 weeks were performed in 203 patients. The midpoint between the percentage area reduction from baseline at 4 weeks in patients healed versus those not healed at 12 weeks was found to be 53%. Subjects with a reduction in ulcer area greater than the 4-week median had a 12-week healing rate of 58%, whereas those with reduction in ulcer area less than the 4-week median had a healing rate of only 9% (P &amp;lt; 0.01). The absolute change in ulcer area at 4 weeks was significantly greater in healers versus nonhealers (1.5 vs. 0.8 cm2, P &amp;lt; 0.02). The percent change in wound area at 4 weeks in those who healed was 82% (95% CI 70–94), whereas in those who failed to heal, the percent change in wound area was 25% (15–35; P &amp;lt; 0.001). CONCLUSIONS—The percent change in foot ulcer area after 4 weeks of observation is a robust predictor of healing at 12 weeks. This simple tool may serve as a pivotal clinical decision point in the care of diabetic foot ulcers for early identification of patients who may not respond to standard care and may need additional treatment.
Comprehensive Textbook of Psychiatry, 6th ed., vols. 1 and 2; Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences and Clinical Psychiatry, 7th ed.; Study Guide and Self-Examination Review for Kaplan and Sadock's Synopsis of Psychiatry, 5th ed
Authors: JEFFREY J. HANSEN
Journal: American Journal of Psychiatry (1996)
Exposure to Pets in Childhood and Risk of Atopic Disorders
Authors: Johannes C. van der Wouden, Roos M. D. Bernsen
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Urinary concentrating ability in patients with Jk(a-b-) blood type who lack carrier-mediated urea transport.
Authors: J M Sands, J J Gargus, O Fröhlich, R B Gunn, J P Kokko
Journal: Journal of the American Society of Nephrology (1992)

Water homeostasis is regulated in large part by the proper operation of the urinary concentrating mechanism. In the renal inner medulla, urea recycling from the inner medullary collecting duct to the inner medullary interstitium is thought to be essential for the production of a concentrated urine; however, it has not been possible to test this hypothesis in humans. Recently, a unique combination of genetic abnormalities has been described: absence of Kidd blood group antigens and absence of carrier-mediated urea transport in erythrocytes. Because animal studies indicate a similarity between urea transport in red blood cells and the nephron, it was postulated that patients without the Kidd antigen might lack facilitated urea transport in their kidneys. Hence, their ability to concentrate urine maximally was measured. Current models of nephron function would predict that in the complete absence of urea transport, the maximal concentrating ability would be around 800 to 900 mosM/kg H2O. Two homozygous patients had a moderate decrease in maximal concentrating ability (UosM,max = 819 mosM/kg H2O); a heterozygote also had some limitation. These studies raise the possibility that the erythrocyte urea transporter and the kidney urea transporter are encoded by a single gene (detected by the mutational loss of the Kidd antigen) and that a lack of facilitated urea transport impairs urea recycling in the kidney and, hence, maximal urinary concentrating ability.
Trajectories of cardiorespiratory fitness in children with and without developmental coordination disorder: a longitudinal analysis
Authors: John Cairney, John Hay, Scott Veldhuizen, Brent E Faught
Journal: British Journal of Sports Medicine (2010)

To compare the longitudinal trajectories of cardiorespiratory fitness (CRF) in children with probable developmental coordination disorder (DCD) with those of typically developing children.School-based study, conducted in a large region of Ontario, Canada. 75 out of a possible 92 schools (83%) consented to participate.A cohort of children, enrolled in grade 4 (mean 9 years 11 months; SD 0.05) at baseline (n=2278) were followed twice-yearly over a 2-year period.The short form of the Bruininks-Oseretsky test of motor proficiency was used to identify children with probable DCD and the Leger shuttle run to measure maximal oxygen uptake (VO(2)max).Mixed-effects modelling was used to estimate the change over time in predicted VO(2)max for both children with probable DCD and typically developing children. For all children, VO(2)max declined over time. Children (boys and girls) with probable DCD not only had lower VO(2)max at baseline compared with typically developing children, VO(2)max declined among these children at a much steeper rate.Although previous research has found children with DCD to have poor CRF compared with typically developing children, most of this work has relied on cross-sectional designs to examine group differences. The results of this study confirm that differences in CRF between children with and without probable DCD persist over time, highlighting the concern that DCD is a risk factor for poor cardiovascular health in children.
Controlled Delivery of Basic Fibroblast Growth Factor Promotes Human Cardiosphere-Derived Cell Engraftment to Enhance Cardiac Repair for Chronic Myocardial Infarction
Authors: Naofumi Takehara, Yoshiaki Tsutsumi, Kento Tateishi, Takehiro Ogata, Hideo Tanaka, Tomomi Ueyama, Tomosaburo Takahashi, Tetsuro Takamatsu, Masanori Fukushima, Masashi Komeda, Masaaki Yamagishi, Hitoshi Yaku, Yasuhiko Tabata, Hiroaki Matsubara, Hidemasa Oh
Journal: Journal of the American College of Cardiology (2008)
Relation between drug treatment and cancer In hypertenslves in the Swedish Trial in Old Patients with Hypertension 2: a 5-year, prospective, randomised, controlled trial
Authors: Lars H Lindholm, Harald Anderson, Tord Ekbom, Lennart Hansson, Jan Lanke, Björn Dahlöf, Ulf de Faire, Kent Forsén, Thomas Hedner, Erland Linjer, Bengt Scherstén, P-O Wester, Torgil R Möller
Journal: The Lancet (2001)
Tolerogenic Dendritic Cells
Authors: Ralph M. Steinman, Daniel Hawiger, Michel C. Nussenzweig
Journal: Annual Review of Immunology (2003)

Dendritic cells (DCs) have several functions in innate and adaptive immunity. In addition, there is increasing evidence that DCs in situ induce antigen-specific unresponsiveness or tolerance in central lymphoid organs and in the periphery. In the thymus DCs generate tolerance by deleting self-reactive T cells. In peripheral lymphoid organs DCs also induce tolerance to antigens captured by receptors that mediate efficient uptake of proteins and dying cells. Uptake by these receptors leads to the constitutive presentation of antigens on major histocompatibility complex (MHC) class I and II products. In the steady state the targeting of DC antigen capture receptors with low doses of antigens leads to deletion of the corresponding T cells and unresponsiveness to antigenic rechallenge with strong adjuvants. In contrast, if a stimulus for DC maturation is coadministered with the antigen, the mice develop immunity, including interferon-gamma-secreting effector T cells and memory T cells. There is also new evidence that DCs can contribute to the expansion and differentiation of T cells that regulate or suppress other immune T cells. One possibility is that distinct developmental stages and subsets of DCs and T cells can account for the different pathways to peripheral tolerance, such as deletion or suppression. We suggest that several clinical situations, including autoimmunity and certain infectious diseases, can be influenced by the antigen-specific tolerogenic role of DCs.
Human Cancer Cells Commonly Acquire DNA Damage during Mitotic Arrest
Authors: W. Brian Dalton, Mandayam O. Nandan, Ryan T. Moore, Vincent W. Yang
Journal: Cancer Research (2007)

Abstract The mitotic checkpoint is a mechanism that arrests the progression to anaphase until all chromosomes have achieved proper attachment to mitotic spindles. In cancer cells, satisfaction of this checkpoint is frequently delayed or prevented by various defects, some of which have been causally implicated in tumorigenesis. At the same time, deliberate induction of mitotic arrest has proved clinically useful, as antimitotic drugs that interfere with proper chromosome-spindle interactions are effective anticancer agents. However, how mitotic arrest contributes to tumorigenesis or antimitotic drug toxicity is not well defined. Here, we report that mitotic chromosomes can acquire DNA breaks during both pharmacologic and genetic induction of mitotic arrest in human cancer cells. These breaks activate a DNA damage response, occur independently of cell death, and subsequently manifest as karyotype alterations. Such breaks can also occur spontaneously, particularly in cancer cells containing mitotic spindle abnormalities. Moreover, we observed evidence of some breakage in primary human cells. Our findings thus describe a novel source of DNA damage in human cells. They also suggest that mitotic arrest may promote tumorigenesis and antimitotic toxicity by provoking DNA damage. [Cancer Res 2007;67(24):11487–92]
Vandetanib, Designed to Inhibit VEGFR2 and EGFR Signaling, Had No Clinical Activity as Monotherapy for Recurrent Ovarian Cancer and No Detectable Modulation of VEGFR2
Authors: Christina M. Annunziata, Amanda J. Walker, Lori Minasian, Minshu Yu, Herbert Kotz, Bradford J. Wood, Katherine Calvo, Peter Choyke, Daniel Kimm, Seth M. Steinberg, Elise C. Kohn
Journal: Clinical Cancer Research (2010)

Abstract Purpose: To evaluate clinical activity and target modulation of vandetanib in women with recurrent ovarian cancer. Experimental Design: A phase II trial of orally administered vandetanib 300 mg daily was designed to include analyses of target inhibition through paired biopsies and dynamic imaging. Core 18-gauge needle biopsies and dynamic contrast-enhanced magnetic resonance imaging were obtained before initiation of therapy and 6 weeks into therapy. Biopsy samples were subjected to reverse-phase protein lysate array endpoint analysis. Cytokine concentrations were measured by enzyme-linked immunosorbent assay in serially collected plasma samples. Results: Twelve patients entered the study, and accrual was terminated in the first stage because of lack of response or disease stabilization beyond 6 months. Adverse events included rash, diarrhea, and prolonged QT interval corrected for heart rate, but not hypertension. Exploratory analyses showed that epidermal growth factor receptor (EGFR) phosphorylation was reduced in the eight paired biopsy sets obtained; vascular endothelial growth factor (VEGF) receptor-2 phosphorylation was not consistently affected nor were dynamic contrast-enhanced MRI permeability and flow parameters. Serial plasma VEGF concentrations were variable and did not significantly change in the 11 patients assessed. Conclusions: Vandetanib 300 mg daily monotherapy had no significant clinical benefit in this disease setting. Proteomic analysis of paired biopsies detected both phosphorylated-EGFR and phosphorylated-VEGF receptor-2 in ovarian tumor tissue, but only phosphorylated-EGFR was measurably inhibited by vandetanib. Clin Cancer Res; 16(2); 664–72