tbuckley/cabot-search huggingface dataset:
Kaposi's sarcoma associated with immunosuppression for bullous pemphigoid
Authors: S.M. HALPERN, R. PARSLEW, R. CERIO, J.T.D. KIRBY, G.R. SHARPE
Journal: British Journal of Dermatology (1997)

Kaposi's sarcoma may occur in transplant recipients on immunosuppressive regimens, but is not well recognized in association with treatment for dermatological disease. We report two cases where multifocal Kaposi's sarcoma developed following iatrogenic immunosuppression with prednisolone and azathioprine for bullous pemphigoid. Both patients were HIV negative and, in one case, lesions regressed both clinically and histologically when immunosuppressive therapy was withdrawn.
Molecular Characterization of Crustacean Visual Pigments and the Evolution of Pancrustacean Opsins
Authors: M. L. Porter, T. W. Cronin, D. A. McClellan, K. A. Crandall
Journal: Molecular Biology and Evolution (2006)

Investigations of opsin evolution outside of vertebrate systems have long been focused on insect visual pigments, whereas other groups have received little attention. Furthermore, few studies have explicitly investigated the selective influences across all the currently characterized arthropod opsins. In this study, we contribute to the knowledge of crustacean opsins by sequencing 1 opsin gene each from 6 previously uncharacterized crustacean species (Euphausia superba, Homarus gammarus, Archaeomysis grebnitzkii, Holmesimysis costata, Mysis diluviana, and Neomysis americana). Visual pigment spectral absorbances were measured using microspectrophotometry for species not previously characterized (A. grebnitzkii = 496 nm, H. costata = 512 nm, M. diluviana = 501 nm, and N. americana = 520 nm). These novel crustacean opsin sequences were included in a phylogenetic analysis with previously characterized arthropod opsin sequences to determine the evolutionary placement relative to the well-established insect spectral clades (long-/middle-/short-wavelength sensitive). Phylogenetic analyses indicate these novel crustacean opsins form a monophyletic clade with previously characterized crayfish opsin sequences and form a sister group to insect middle-/long-wavelength–sensitive opsins. The reconstructed opsin phylogeny and the corresponding spectral data for each sequence were used to investigate selective influences within arthropod, and mainly "pancrustacean," opsin evolution using standard dN/dS ratio methods and more sensitive techniques investigating the amino acid property changes resulting from nonsynonymous replacements in a historical (i.e., phylogenetic) context. Although the conservative dN/dS methods did not detect any selection, 4 amino acid properties (coil tendencies, compressibility, power to be at the middle of an α-helix, and refractive index) were found to be influenced by destabilizing positive selection. Ten amino acid sites relating to these properties were found to face the binding pocket, within 4 Å of the chromophore and thus have the potential to affect spectral tuning.
Fibroblast and transforming growth factor expression in the cardiac myocyte
Authors: P. Cummins
Journal: Cardiovascular Research (1993)

Journal Article Fibroblast and transforming growth factor expression in the cardiac myocyte Get access Peter Cummins Peter Cummins British Heart Foundation Molecular Cardiology Research Group, Department of Physiology, The Medical School, University of Birmingham, Birmingham B15 2TJ, United Kingdom: Dr P Cummins. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 7, July 1993, Pages 1150–1154, https://doi.org/10.1093/cvr/27.7.1150 Published: 01 July 1993 Article history Received: 05 August 1992 Accepted: 10 September 1992 Published: 01 July 1993
Authors’ response to Metzdorf<i>et al</i>
Authors: Christine R Jenkins, Richard Beasley
Journal: Thorax (2013)

We appreciate the contribution to this discussion from Metzdorf et al 1 , and the efforts made by the company to assess the safety of the Handihaler and Respimat through pooling datasets from randomised controlled trials.We would like reassurance that the pooled analysis of the three 1-year and one 6-month placebocontrolled trials with Spiriva Respimat detailed on the product information website was based on an intention to treat analysis, and involved no reclassification of deaths.This analysis provides essential information for prescribers and should be published.We agree that patient-level data are preferable to pooled population data, but the value of such an analysis is reduced if undertaken on a modified dataset.To date we consider the pharmacokinetic data regarding the comparative safety of tiotropium delivered by Respimat compared with the Handihaler is inconclusive and more work is needed.Based on the different deposition, absorption and physical properties of solutions and dry powders, we do not believe that a difference in systemic absorption and cardiovascular risk between these two would be implausible.We are not convinced by their interpretation of the 2010 abstract that patients enrolled in the tiotropium trial programme have a comorbidity profile comparable with the general chronic obstructive pulmonary disease (COPD) population, as there are insufficient details provided regarding diagnostic definitions used and no data is presented on the proportion of patients with rhythm disorders.Furthermore, comparison is required with a COPD population of similar severity to that enrolled in the tiotropium clinical trial programme.It is evident that the exclusion of patients with moderate to severe renal impairment, or a recent myocardial infarction, heart failure or rhythm disorder, results in findings that are poorly generalisable to patients with severe COPD.As a result it would be prudent to recommend that tiotropium Handihaler should only be prescribed to the subgroups of patients in whom tiotropium Handihaler has been 782
Natural Product Inspired N‐Terminal Hsp90 Inhibitors: From Bench to Bedside?
Authors: Anuj Khandelwal, Vincent M. Crowley, Brian S. J. Blagg
Journal: Medicinal Research Reviews (2015)

Abstract The 90 kDa heat shock proteins (Hsp90) are responsible for the conformational maturation of nascent polypeptides and the rematuration of denatured proteins. Proteins dependent upon Hsp90 are associated with all six hallmarks of cancer. Upon Hsp90 inhibition, protein substrates are degraded via the ubiquitin‐proteasome pathway. Consequentially, inhibition of Hsp90 offers a therapeutic opportunity for the treatment of cancer. Natural product inhibitors of Hsp90 have been identified in vitro, which have served as leads for the development of more efficacious inhibitors and analogs that have entered clinical trials. This review highlights the development of natural product analogs, as well as the development of clinically important inhibitors that arose from natural products.
Decreased Pulmonary Transvascular Fluid Filtration in Awake Newborn Lambs after Intravenous Furosemide
Authors: Richard D. Bland, Douglas D. McMillan, Michael A. Bressack
Journal: Journal of Clinical Investigation (1978)

We studied the effect of furosemide on pulmonary transvascular filtration of fluid and microvascular permeability to plasma proteins by measuring steady-state lung lymph flow and protein flow, pulmonary arterial and left atrial pressures in nine 1-wk-old unanesthetized lambs before and after rapid intravenous infusion of furosemide, 1 mg/kg in 10 experiments and 8 mg/kg in 5 experiments. With rapid diuresis induced by furosemide (an eightfold increase in urine flow), lung vascular pressures decreased, protein concentrations of lymph and plasma increased, and there was a consistent decrease in lymph flow and lymph protein flow, more pronounced after the larger dose. Five additional lambs received 8 mg/kg of furosemide intravenously in the presence of saline-induced pulmonary edema; in these experiments, the decrease in vascular pressures, increase in transvascular protein gradient, and decrease in lymph flow were greater than in lambs without pulmonary edema. These findings suggest that furosemide decreases transvascular filtration of fluid in the lung by diminishing the transvascular hydraulic pressure gradient and increasing the transvascular gradient for protein osmotic pressure. In five acute experiments on anesthetized lambs with kidneys removed, 8 mg/kg of intravenous furosemide decreased lymph flow one-half as much as it did in the presence of kidneys, with no change in lung vascular pressures or protein concentrations. The results of experiments in lambs without kidneys are consistent with a reduction in the vascular surface area for exchange of fluid and protein in the lung.
Family History of Type 2 Diabetes Is Associated With Increased Carotid Artery Intimal-Medial Thickness in Mexican Americans
Authors: W.H. Linda Kao, Wen-Chi Hsueh, David L. Rainwater, Daniel H. O’Leary, Ikhide G. Imumorin, Michael P. Stern, Braxton D. Mitchell
Journal: Diabetes Care (2005)

To evaluate whether the joint risk of diabetes and atherosclerosis tracked within families, we assessed the correlation between a family history of diabetes and intimal-medial thickness (IMT) of the common carotid artery (CCA).Study subjects included 620 nondiabetic individuals from 24 families enrolled in the San Antonio Family Heart Study. The thickness of the far walls of the CCA was measured by B-mode ultrasonography. Statistical analyses included familial correlations to account for the nonindependence of family data.After adjusting for sex, age, and IMT reader effects, the heritability of IMT in this population was 16% (P = 0.009). Using a more comprehensive family history score that accounted for diabetes status of the individual's parents and older siblings, we observed a significant correlation between family history score and increased CCA IMT (0.006 mm increase in CCA IMT for every point increase of diabetes family history score, P = 0.016). This association remained even after further adjustment for BMI, smoking, and fasting insulin and glucose levels. After adjusting for several cardiovascular risk factors, the mean CCA IMT in those with high family history scores for diabetes was still 0.037 mm thicker than those with low family history scores for diabetes (P = 0.040).These results suggest that the genetic contribution to CCA IMT variability is modest. Also, the small increase in subclinical atherosclerosis observed even among nondiabetic Mexican Americans with a positive family history of diabetes is probably transmitted along with the risk of diabetes through shared etiologic risk factors between diabetes and cardiovascular disease.
RS3PE syndrome. The relation with HLA B7
Authors: C. PEASE
Journal: Annals of the Rheumatic Diseases (2000)

Normal values of laboratory tests in elderly onset psoriatic arthritisI read with interest the article recently published by Punzi et al. 1 The results shown in this study demonstrate higher levels of acute phase reaction markers such as ESR and CRP in elderly onset psoriatic arthritis patients (EOPsA) than those displayed by young onset psoriatic arthritis patients (YOPsA).The authors included 16 EOPsA (>60 years) and 50 YOPsA (<60 years).I would like to comment that the information regarding normal values was restricted to the following words "CRP, normal values <0.6 mg/dl", no other information is given.It is not possible to know how and from whom these normal values were obtained.Even if a commercial test that includes their own controls was used, it is clear that you will need to test groups of normal subjects that cover the age spectrum of both groups of patients EOPsA and YOPsA.This strategy will allow you to estimate the influence of age in the higher levels of ESR and CRP exhibited by EOPsA.The inclusion of this control group of normal subjects is also recommended because YOPsA does not belong to the same age cohort that EOPsA does, and in fact, EOPsA represents a group of survivors from their original birth cohort more that YOPsA does.
Livedoid vasculopathy: long-term follow-up results following hyperbaric oxygen therapy
Authors: W-H. Juan, Y-S. Chan, J.C. Lee, L-C. Yang, H-S. Hong, C-H. Yang
Journal: British Journal of Dermatology (2005)

Background Livedoid vasculopathy, also known as atrophie blanche, is a recurrent painful vasculopathy appearing mostly on the lower limbs. Treatment is challenging and relapses are frequent. Objectives To analyse the long‐term effect and safety of hyperbaric oxygen (HBO) therapy in treating livedoid vasculopathy. Methods Twelve patients with active livedoid vasculopathy were included in this study. All patients underwent HBO therapy five times a week. Each week photographs were taken and the total dose of analgesics was recorded. Side‐effects were documented and assessed. Recurrence was defined as the presence of skin ulceration. Results Of the eight patients who completed the treatment, resumption of ambulation and reduction of analgesics were achieved at an average of 4·9 HBO therapy sessions. Leg ulcers in all eight patients healed completely at a mean of 3·4 weeks (range 2–5 weeks). Six patients suffered relapses of ulceration and responded to additional HBO therapy. No significant side‐effects were found. Conclusions HBO is a relatively safe, fast and effective method to treat patients with livedoid vasculopathy.
EphA2 Mediates Ligand-Dependent Inhibition and Ligand-Independent Promotion of Cell Migration and Invasion via a Reciprocal Regulatory Loop with Akt
Authors: Hui Miao, Da-Qiang Li, Amitava Mukherjee, Hong Guo, Aaron Petty, Jennifer Cutter, James P. Basilion, John Sedor, Jiong Wu, David Danielpour, Andrew E. Sloan, Mark L. Cohen, Bingcheng Wang
Journal: Cancer Cell (2009)
Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study
Authors: Francois Raffi, Anita Rachlis, Hans-Jürgen Stellbrink, W David Hardy, Carlo Torti, Chloe Orkin, Mark Bloch, Daniel Podzamczer, Vadim Pokrovsky, Federico Pulido, Steve Almond, David Margolis, Clare Brennan, Sherene Min
Journal: The Lancet (2013)
Study of Erythrocyte Aggregation by Blood Viscometry at Low Shear Rates Using a Balance Method
Authors: A. M. BENIS, J. LACOSTE
Journal: Circulation Research (1968)

Abalance method was used to investigate the viscometric behavior and aggregation properties of blood at very low shear rates. The system was essentially a parallel-plate viscometer, consisting of a thin brass plate suspended by a fine wire from one end of an analytical beam balance. The yield shear stress of a sample was obtained directly by recording stress relaxation curves. Results were obtained for homogeneous Newtonian and non-Newtonian fluids and for blood and various red cell suspensions. It was found that human and canine blood behave as fluids exhibiting a yield stress. Suspensions of red cells in saline had much smaller values of yield stress, which is consistent with greatly diminished erythrocyte aggregation when fibrinogen is lacking. Measured values of the yield stress were in the range of 0.001 to 0.1 dynes/cm 2 .
Detection of human T lymphotrophic virus type I (HTLV-I) proviral DNA and analysis of T cell receptor V beta CDR3 sequences in spinal cord lesions of HTLV-I-associated myelopathy/tropical spastic paraparesis.
Authors: H Hara, M Morita, T Iwaki, T Hatae, Y Itoyama, T Kitamoto, S Akizuki, I Goto, T Watanabe
Journal: The Journal of Experimental Medicine (1994)

Identification of the localization of human T lymphotrophic virus type I (HTLV-I) proviral DNA in the central nervous system (CNS) is crucial to the understanding of the pathogenesis of HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) pathogenesis. We have developed a sensitive detection method, called two-step polymerase chain reaction (PCR) in situ hybridization, which enabled us to detect the HTLV-I proviral DNA in paraffin-embedded spinal cord tissue sections from HAM/TSP patients. HTLV-I proviral DNA was detected only in the nucleus of lymphocytes that had infiltrated into the spinal cord. However, no proviral DNA was amplified in any neuronal cells, including neurons and glial cells. This indicates that the demyelination of the spinal cord by HTLV-I as a result of viral infection of oligodendrocytes or neuronal cells is unlikely. The T cell receptor V beta gene sequence from lymphocytes in the spinal cord lesions taken from the same HAM/TSP autopsy cases revealed unique and restricted CDR3 motifs, CASSLXG(G) (one-letter amino acid. X is any amino acid), CASSPT(G), and CASSGRL which are similar to those described in T cells from brain lesions of multiple sclerosis (MS) and in a rat T cell clone derived from experimental allergic encephalomyelitis (EAE) lesions. The present results suggest that T cells containing restricted V beta CDR3 motifs, which are also found in MS and EAE, become activated upon HTLV-I infection and infiltrate into the spinal cord lesions of HAM/TSP patients.
Effect of Neuraminidase on Growth of a 3-Methylcholanthrene-Induced Fibrosarcoma in Normal and Immunosuppressed Syngeneic Mice<xref ref-type="fn" rid="FN1">2</xref>
Authors: Richard L. Simmons, Angelyn Rios, Prasanta K. Ray, Goran Lundgren
Journal: JNCI Journal of the National Cancer Institute (1971)

Treatment of a weakly immunogenic 3-methylcholanthrene-induced fibrosarcoma (MC-42) with Vibrio cholerae neuraminidase (VCN) in vitro interfered with growth of the tumor cells in syngeneic C3H/HeJ female mice. Palpable tumors did not appear in some recipients, and many of the tumors which did appear spontaneously regressed. The effect could be detected at all tumor cell doses and at low concentrations of VCN. The recipients that survived were frequently immune to subsequent inoculations of large numbers of MC-42 cells, but tolerated the growth of immunologically distinct, 3-methylcholanthrene-induced fibrosarcomas (MC-43). The inhibitory effect of VCN treatment on tumor growth was abrogated by heat inactivation of the enzyme or by incubation of the enzyme with sialic acid—a negative feedback inhibitor of neuraminidase. VCN-treated tumor cells grew as rapidly as normal cells in immunosuppressed recipients. The results are consistent with the hypothesis that removal of the terminal sialic acid residues from the cell surface does not interfere with the intrinsic growth potential of the tumor cells, but that it increases the immunogenicity of tumor-specific transplantation antigens on the cell surface. Increased tumor immunogenicity is probably the result of changes on the cell surface which make the treated cells more susceptible to immunologic processing by the recipient.
Pseudoaneurysm Formation and Repair After Mohs Micrographic Surgery
Authors: Scott W. Dunbar, Eva A. Hurst
Journal: JAMA Dermatology (2014)

<h3>Importance</h3> Pseudoaneurysm is a well-known complication of trauma and iatrogenic injury to the vasculature. We report 3 cases of postsurgical pseudoaneurysm after Mohs surgery. <h3>Observations</h3> Three patients who underwent Mohs surgery for nonmelanoma skin cancers presented between 2 and 4 weeks after surgery with several days’ history of painful, enlarging, pulsatile subcutaneous masses. The lesions were diagnosed as postsurgical pseudoaneurysm. During surgical repair of each lesion, we identified vascular outpouchings that were connected to the injured arteries by sinus tracts. In all 3 patients, we ligated the affected artery and the neck of each lesion and reapproximated the skin. All wounds healed well without further recurrence. <h3>Conclusions and Relevance</h3> Most reported cases of pseudoaneurysm formation in the head and neck involve the superficial temporal artery and its branches, and they typically occur secondary to blunt force trauma. Our cases are unique in that they included 1 case of a superficial temporal lesion but also 2 cases outside this system: 1 of the lateral nasal artery and 1 of the angular artery. We propose operative repair as the treatment of choice for facial pseudoaneurysms that complicate dermatologic surgery.
Pharmacokinetics of Hedgehog Pathway Inhibitor Vismodegib (GDC-0449) in Patients with Locally Advanced or Metastatic Solid Tumors: the Role of Alpha-1-Acid Glycoprotein Binding
Authors: Richard A. Graham, Bert L. Lum, Sravanthi Cheeti, Jin Yan Jin, Karin Jorga, Daniel D. Von Hoff, Charles M. Rudin, Josina C. Reddy, Jennifer A. Low, Patricia M. LoRusso
Journal: Clinical Cancer Research (2011)

Abstract Purpose: In a phase I trial for patients with refractory solid tumors, hedgehog pathway inhibitor vismodegib (GDC-0449) showed little decline in plasma concentrations over 7 days after a single oral dose and nonlinearity with respect to dose and time after single and multiple dosing. We studied the role of GDC-0449 binding to plasma protein alpha-1-acid glycoprotein (AAG) to better understand these unusual pharmacokinetics. Experimental Design: Sixty-eight patients received GDC-0449 at 150 (n = 41), 270 (n = 23), or 540 (n = 4) mg/d, with pharmacokinetic (PK) sampling at multiple time points. Total and unbound (dialyzed) GDC-0449 plasma concentrations were assessed by liquid chromatography/tandem mass spectrometry, binding kinetics by surface plasmon resonance–based microsensor, and AAG levels by ELISA. Results: A linear relationship between total GDC-0449 and AAG plasma concentrations was observed across dose groups (R2 = 0.73). In several patients, GDC-0449 levels varied with fluctuations in AAG levels over time. Steady-state, unbound GDC-0449 levels were less than 1% of total, independent of dose or total plasma concentration. In vitro, GDC-0449 binds AAG strongly and reversibly (KD = 13 μmol/L) and human serum albumin less strongly (KD = 120 μmol/L). Simulations from a derived mechanistic PK model suggest that GDC-0449 pharmacokinetics are mediated by AAG binding, solubility-limited absorption, and slow metabolic elimination. Conclusions: GDC-0449 levels strongly correlated with AAG levels, showing parallel fluctuations of AAG and total drug over time and consistently low, unbound drug levels, different from previously reported AAG-binding drugs. This PK profile is due to high-affinity, reversible binding to AAG and binding to albumin, in addition to solubility-limited absorption and slow metabolic elimination properties. Clin Cancer Res; 17(8); 2512–20. ©2011 AACR.
The struggle against sins
Authors: John Main
Journal: Journal of the Royal Society of Medicine (2010)

Your highlighting of the three deadly sins of hierarchy, etiquette and conformity as barriers to good prescribing seems highly appropriate.1 These, of course, are not new, although hierarchy (at least in physicianly specialties) may be somewhat less of a problem than it used to be. On my first ever attachment as a student to a medical ‘firm’ (remember them?) in the Royal Infirmary of Edinburgh in the late 1970s, one particular weekly consultant round was extremely hierarchical, with the massed retinue speaking only when spoken to. Many prescribing decisions were made and carefully entered by the house officer on the drug chart at the foot of the bed. The registrar took careful notes.