tbuckley/cabot-search huggingface dataset:
Intralesional Rituximab in the Treatment of Refractory Oral Pemphigus Vulgaris
Authors: Keshavamurthy Vinay, Amrinder J. Kanwar, Ankit Mittal, Sunil Dogra, Ranjana W. Minz, Takashi Hashimoto
Journal: JAMA Dermatology (2014)

reatment of oral pemphigus vulgaris (PV) remains a challenge because of the chronic, persistent nature of this disease.The healing process of oral ulcers is much slower than that of cutaneous lesions, which require slow tapering of corticosteroid therapy. 1 Various topical therapies for oral lesions in PV, including corticosteroids, cyclosporine, and tacrolimus, have been used without any significant outcome. 1 Rituximab, a chimeric monoclonal antibody to CD20, has been approved by the US Food and Drug Administration to treat CD20-positive non-Hodgkin lymphoma.Intralesional rituximab treatment has been used successfully in a few studies of primary cutaneous B-cell lymphoma. 2,3Because previous studies have proven the efficacy of intravenous rituximab in the treatment of the pemphigus group of disorders, 4,5 the same efficacy might be obtained by intralesional administration of rituximab in selected cases of oral PV.In this case series, we evaluated for the first time, to our knowledge, the usefulness of intralesional rituximab administration in patients with refractory oral PV. Methods PatientsAfter providing written informed consent, 3 patients with oral PV who satisfied the inclusion criteria were recruited in March 2013.
IN VIVO MONITORING OF RIT IN LYMPHOMA BY QUANTITATION OF PHOSPATE METABOLITES WITH 31P-NMR
Authors: Dorothy A. Adams, Gerald L. DeNardo, Sally J. DeNardo
Journal: Clinical Nuclear Medicine (1984)

Monitoring of the effects of radioimmunopharmaceuticals on tumor tissue is fundamental to development of rational radioimmunotherapy (RIT) schemes employing radiolabeled monoclonal antibodies (and antibody fragments) specific for human tumors. The rapid advances in nuclear magnetic resonance (NMR) spectroscopy make it an attractive candidate for serial measurement of metabolic events during RIT. Preliminary to this effort, we have initiated in vivo surface coil 31P-NMR measurements of the human non-Hodgkins lymphoma (RAJI tumor) implanted in the hindquarter of nude mice in the presence and absence of 131I-labeled monoclonal antibody specific for this tumor. ATP/Pi ratios and tissue pH as determined from 31P spectra have been correlated with tumor volumes and radiation-induced tissue damage. During these preliminary experiments, we have noted that the effects of the radiation dose, calculated to be curative, are non-uniform throughout the tissue mass. Furthermore, careful assessment of tumor volumes indicates that tumors vary widely in size and configuration as a function of time. It is clear that to thoroughly evaluate the effects of radiolabeled monoclonal antibodies and ultimately, labeled antibody fragments on human tumors in the mouse model, spatial resolution of metabolites within tissue slices through the tumor is required. Preliminary experiments demonstrated the feasibility of spatial discrimination in tumor tissue. We conclude that 31P-NMR may prove useful as a predictive tool for selecting dose regimens and setting curative doses in RIT.
PSYCHOSES ASSOCIATED WITH SYDENHAM'S CHOREA
Authors: E. M. HAMMES
Journal: JAMA (1922)

The syndrome of chorea is usually classified under four main groups: (1) the infectious group, Sydenham's chorea and chorea gravidarum; (2) the psychogenic and hereditary group, comprising the spasmodic tics and Huntington's chorea; (3) the myokymia disorders, including symptomatic fibrillary twitchings and Friedreich's myoclonus multiplex, and (4) choreiform movements associated with organic conditions, occurring in hemiplegias, in the chronic choreas of childhood and in other structural brain disturbances, such as those associated with epidemic encephalitis. Many interesting clinical pictures have been reported, accompanying the recent epidemic of encephalitis. Bizarre muscular movements of almost every kind have been described. In a series of 154 cases, I have observed choreiform movements eight times. In one of these, a diagnosis of Sydenham's chorea was made during the first week, after which the patient became lethargic, complained of diplopia and presented the usual picture of epidemic encephalitis. Another patient, during the third week of
Medical aspects of North Sea oil
Authors: R. J Thompson
Journal: BMJ (1975)

jouRNAL 25 ocTOBER 1975 22?out accurate fracture reduction, and move- ment of bone within the wires can take place.In a bone as heavily stressed as the tibia this is almost impossible to avoid.In other situa- tions, as for instance the fibular component of certain ankle fracture-dislocations, they can be of very great value.It would be a pity for the appropriate use of encirclage wiring in fracture treatment to be discredited by further repetition of this long-standing misapprehension concerning the reasons for its failure when used inappropriately.
Identification of loci associated with late-onset psoriasis using dense genotyping of immune-related regions
Authors: H.L. Hébert, J. Bowes, Rh.Ll. Smith, E. Flynn, R. Parslew, A. Alsharqi, N.J. McHugh, J.N.W.N. Barker, C.E.M. Griffiths, A. Barton, R.B. Warren
Journal: British Journal of Dermatology (2014)

Chronic plaque psoriasis can be subdivided into two groups according to the age of onset: type 1 (early onset, before 40 years) and type 2 (late onset, at or beyond 40 years). So far, 36 genetic loci have been associated with early‐onset psoriasis in genome‐wide association studies of white populations, while few studies have investigated genetic susceptibility to late‐onset psoriasis. To characterize the genetics underpinning late‐onset psoriasis. We genotyped 543 cases of late‐onset psoriasis and 4373 healthy controls using the Immunochip array, a dense genotyping chip containing single‐nucleotide polymorphisms previously associated with autoimmune diseases. Imputation using SNP2HLA and stepwise logistic regression analysis was performed for markers spanning the human leucocyte antigen gene region. Two loci (HLA‐C and IL12B) previously associated with early‐onset psoriasis showed significant association at a genome‐wide threshold in the current study (P <5 × 10−8). Six more loci (TRAF3IP2, IL23R, RNF114, IFIH1, IL23A and HLA‐A) showed study‐wide significant association (P <2·3 × 10−5; calculated using Genetic type 1 error calculator). Additionally, we identified an association at IL1R1 on chromosome 2q13, which is not associated with early‐onset disease. This is the largest study to date of genetic loci in late‐onset psoriasis, and demonstrates the overlap that exists with early‐onset psoriasis. It also suggests that some loci are associated exclusively with late‐onset psoriasis.
A Clinical Lecture ON ARTHROTOMY OF THE KNEE FOR THE REMOVAL OF INFLAMED SYNOVIAL FRINGES AND OF THE PADS OF MALGAIGNE: Delivered at St. Bartholomew's Hospital
Authors: C. B. Lockwood
Journal: BMJ (1909)

ETmz BMmA 7 Within four months I operated upon her five times.The bony ankylosed aukle was first straightened by the removal of a large wedge with its base obliquely outwards.Next a wedge was
Aging and Fountain-of-Youth Hormones
Authors: Paul M. Stewart
Journal: New England Journal of Medicine (2006)

The search for eternal youth is vibrant in North America. In this search, it is all too easy to ascribe the aging process to endocrines. Although the secretion of growth hormone falls by about 12% per decade after middle age, perhaps the greatest attention has focused on sex steroids, since estrogen secretion falls abruptly in postmenopausal women, and testosterone levels decline with age, though more gradually, in men1,2 (Figure 1A). Levels of the adrenal sex steroid dehydroepiandrosterone (DHEA) and its sulfate ester fall progressively after 30 years of age, and after 60 years of age are less than half . . .
Abstract 2436: AGS-16M8F is a novel antibody drug conjugate (ADC) for treating renal and liver cancers
Authors: Jean M. Gudas, Michael Torgov, Zili An, Xiao- Chi Jia, Karen J. Morrison, Robert K. Morrison, Peng Yang, Arthur B. Raitano, Steven B. Kanner, Aya Jakobovits
Journal: Cancer Research (2010)

Abstract AGS-16 is a novel transmembrane antigen discovered by Agensys using transcription profiling and is expressed in kidney, liver and other cancers. A fully human IgG2k monoclonal antibody that binds to AGS-16 with high affinity was conjugated to the anti-microtubulin drug monomethyl auristatin F (MMAF) via a noncleavable maleimidocaproyl (mc) linker to yield the antibody drug conjugate, AGS-16M8F. AGS-16M8F was evaluated for binding affinity, species cross reactivity and cell cytotoxicity in vitro. Its’ anti-tumor activity was investigated using multiple established patient-derived and cell line models of renal clear cell carcinomas. The pharmacokinetics (PK) of AGS-16M8F was evaluated in mice. In addition, the expression of AGS-16 protein in patient kidney and liver cancer specimens was confirmed using IHC. AGS-16M8F bound with high affinity (Kd = 0.3 nM) to both human and cynomolgus monkey AGS-16 orthologs. Following cell surface binding, AGS-16M8F was internalized and trafficked to lysosomes leading to catabolism and release of active drug metabolite. AGS-16M8F mediated potent cell cytotoxicity in vitro and led to significant and prolonged growth inhibition or complete eradication of multiple established renal cancer xenograft models, including those grown orthotopically. Pharmacokinetic analysis of AGS-16M8F in mice demonstrated ADC stability. IHC analysis confirmed that AGS-16 was highly expressed in over 80% of renal clear cell cancers and 33% of hepatocellular carcinomas. When considered together these data indicate that AGS-16M8F is a promising therapeutic ADC for the treatment of renal and other AGS-16 expressing cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2436.
Do Introns Favor or Avoid Regions of Amino Acid Conservation?
Authors: Toshinori Endo, Alexei Fedorov, Sandro J. de Souza, Walter Gilbert
Journal: Molecular Biology and Evolution (2002)

Are intron positions correlated with regions of high amino acid conservation? For a set of ancient conserved proteins, with intronless prokaryotic but intron-containing eukaryotic homologs, multiple sequence alignments identified residues invariant throughout evolution. Intron positions between codons show no preferences. However, introns lying after the first base of a codon prefer conserved regions, markedly in glycines. Because glycines are in excess in conserved regions, this behavior could reflect phase-one introns entering glycine residues randomly in the ancestral sequences. Examination of intron positions within codons of evolutionarily invariable amino acids showed that roughly 50% of these introns are bordered by guanines at both 5′- and 3′-ends, 25% have a G only before the intron, and 5% have a G only after the intron, whereas about 20% are bordered by nonguanine bases.
Cytokines and smooth muscle cells in atherosclerosis
Authors: J. Nilsson
Journal: Cardiovascular Research (1993)

Journal Article Cytokines and smooth muscle cells in atherosclerosis Get access Jan Nilsson Jan Nilsson King Gustaf Vth Research Institute, 'Box 60004, 104 01 Stockholm, Sweden: Dr J Nilsson. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 7, July 1993, Pages 1184–1190, https://doi.org/10.1093/cvr/27.7.1184 Published: 01 July 1993 Article history Received: 14 April 1992 Accepted: 17 July 1992 Published: 01 July 1993
Silver aids healing in the sterile skin wound: experimental studies in the laboratory rat
Authors: A.B.G. LANSDOWN, B. SAMPSON, P. LAUPATTARAKASEM, A. VUTTIVIROJANA
Journal: British Journal of Dermatology (1997)

Incisional wounds 15 mm long were induced surgically in the back skin of young adult Wistar rats. They were sutured and used as an experimental model in the therapeutic evaluation of daily applications of 0.5 mL, of silver nitrate (SN) at 0.01. 0.1 or 1·0% w/v aqueous solution, or 0·5 g silver sulphadiazine (SSD) over a 10‐day period. Control wounds received deionized water only. The silver preparations were not toxic but SN did stain the hair and superficial layers of the stratum corneum. The wounds remained microbiologically clean. Wounds exposed to SN (0·1 or 1·0%) or SSD healed more rapidly than controls. From about the fourth day of treatment, we noted a more rapid exteriorization of sutures, improved wound closure and an earlier loss of scabs and wound debris. Silver treatment appeared to reduce the inflammatory and granulation tissue phases of healing and enhance epidermal repair. Silver from SN was deposited as silver sulphide in extrafollicular hair shafts and superficial aspects of the skin and wound debris but not at deeper levels. Silver uptake was four‐fold higher in damaged skin than in intact tissue. SSD was absorbed by intact and wounded skin but the silver did not precipitate as silver sulphide and its localization in the tissue is not known. Uptake of silver from SN or SSD was associated wilh changes in the concentrations of zinc and calcium in the skin. Zinc levels were depressed during the inflammatory and proliferative phases of healing and then increased. Zinc concentrations had normalized by 10 days when wound healing was achieved. Calcium levels remained higher than normal throughout the observation period. The mechanism of action of silver in advancing wound healing in the rat is unclear. Its ability to reduce the inflammatory and granulation phases of healing, and to invoke metallothionein production and influence metal ion binding are possibly important.
Do socioeconomic differences in mortality persist after retirement? 25 Year follow up of civil servants from the first Whitehall study
Authors: M G Marmot, M. J Shipley
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To assess the risk of death associated with work based and non-work based measures of socioeconomic status before and after retirement age. <b>Design</b>: Follow up study of mortality in relation to employment grade and car ownership over 25 years. <b>Setting</b>: The first Whitehall study. <b>Subjects</b>: 18 133 male civil servants aged 40–69 years who attended a screening examination between 1967 and 1970. <b>Main outcome measure</b>: Death. <b>Results</b>: Grade of employment was a strong predictor of mortality before retirement. For men dying at ages 40–64 the lowest employment grade had 3.12 times the mortality of the highest grade (95% confidence interval 2.4 to 4.1). After retirement the ability of grade to predict mortality declined (rate ratio 1.86; 1.6 to 2.2). A non-work based measure of socioeconomic status (car ownership) predicted mortality less well than employment grade before retirement but its ability to predict mortality declined less after retirement. Using a relative index of inequality that was sensitive to the distribution among socioeconomic groups showed employment grade and car ownership to have independent associations with mortality that were of equal magnitude after retirement. The absolute difference in death rates between the lowest and highest employment grades increased with age from 12.9 per 1000 person years at ages 40–64 to 38.3 per 1000 at ages 70–89. <b>Conclusions</b>: Socioeconomic differences in mortality persist beyond retirement age and in magnitude increase with age. Social differentials in mortality based on an occupational status measure seem to decrease to a greater degree after retirement than those based on a non-work measure. This suggests that alongside other socioeconomic factors work itself may play an important part in generating social inequalities in health in men of working age. <h3>Key messages</h3> Relative differences in mortality between low and high employment grades are less after retirement, suggesting the importance of work in generating inequalities in health A non-work based measure of socioeconomic status (after adjustment for employment grade) continues to predict relative differences in mortality after retirement Absolute differences in mortality between less and more advantaged groups increase at older ages
Penicillamine Therapy for Hepatolenticular Degeneration
Authors: Irmin Sternlieb, I. Herbert Scheinberg
Journal: JAMA (1964)

Ingestion of copper was reduced and its excretion was enhanced pharmacologically, principally by the administration of penicillamine, in 33 patients with hepatolenticular degeneration, of whom eight were asymptomatic. Concomitant clinical improvement was noted most markedly and regularly in the neurological manifestations of the disease, whereas the psychiatric and hepatic disturbances lessened in some individuals, but worsened in others. Clinical manifestations did not develop in the asymptomatic patients. The administration of penicillamine was occasionally accompanied by fever and several types of skin eruptions, and, less commonly, by hematological and renal reactions.
P1-12-13: Comparative Pharmacokinetics (PK) of Trastuzumab Emtansine (T-DM1) in Patients Who Have or Who Have Not Received Prior Treatment for Human Epidermal Growth Factor 2 (HER2)-Positive Metastatic Breast Cancer (MBC).
Authors: B Wang, P Conte, LA Casanova, Vinholes JJ da Fonseca, OM Saad, J-H Yi, M Gupta, C Song, SR Olsen, EA Perez, S Girish
Journal: Cancer Research (2011)

Abstract Background: T-DM1, an antibody-drug conjugate composed of trastuzumab, a stable linker, and the cytotoxic agent DM1, is in development for the treatment of HER2−positive cancers. Single-agent T-DM1 3.6 mg/kg every 3 weeks (q3w) has demonstrated clinical activity in 2 phase II studies (TDM4258g and TDM4374g) in patients with pretreated HER2−positive MBC. The efficacy and safety of T-DM1 vs trastuzumab + docetaxel was investigated in patients with no prior MBC treatment in the randomized phase II study TDM4450g/BO21976. Here we report the PK of T-DM1 from that study and compare these data with those from studies that enrolled pretreated patients. Methods: In all 3 studies, PK parameters, including maximum concentration (Cmax), area under the concentration-time curve (AUC), terminal half-life (t½), steady-state volume of distribution (Vss), and clearance (CL) were estimated by noncompartmental analysis (NCA) for serum T-DM1, serum total trastuzumab (conjugated and unconjugated), and plasma DM1. The effects of baseline trastuzumab and HER2 extracellular domain (ECD) concentration on T-DM1 exposure were explored and the relationship between T-DM1 exposure and clinical response (objective response rate [ORR] and progression-free survival [PFS]) was modeled. Results: T-DM1 PK from evaluable patients enrolled in 3 studies are shown in Table 1. No significant correlations were observed between efficacy (as measured by ORR) and T-DM1 exposure (AUC, Cmax) after administration of T-DM1 to pretreated patients; efficacy-exposure analyses (ORR and PFS) for previously untreated patients will be presented. Patients with measurable concentrations of trastuzumab at baseline had a greater AUC during cycle 1; however, this did not impact ORR. Baseline circulating HER2 ECD concentrations also had no effect on ORR for pretreated patients. The impact of baseline trastuzumab and HER2 ECD concentrations on ORR and PFS in previously untreated patients will be presented. Conclusions: Single-agent T-DM1 has similar PK in patients who have received prior therapy for MBC and in those who have not. The PK of T-DM1 was not affected by prior trastuzumab treatment or by circulating HER2 ECD, and no significant correlations were observed between efficacy (ORR) and T-DM1 exposure (AUC, Cmax) or HER2 ECD for pretreated patients. The relationships between efficacy and T-DM1 exposure and HER2 ECD concentrations will be presented for patients without prior MBC treatment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-13.
Points: Measles immunisation
Authors: A G M Campbell
Journal: BMJ (1984)

<h3>Objective</h3> The goal of these studies is to discover novel urinary biomarkers of lupus nephritis (LN). <h3>Methods</h3> Urine from systemic lupus erythematosus (SLE) patients was interrogated for 1000 proteins using a novel, quantitative planar protein microarray. Hits were validated in an independent SLE cohort with inactive, active non-renal (ANR) and active renal (AR) patients, in a cohort with concurrent renal biopsies, and in a longitudinal cohort. Single-cell renal RNA sequencing data from LN kidneys were examined to deduce the cellular origin of each biomarker. <h3>Results</h3> Screening of 1000 proteins revealed 64 proteins to be significantly elevated in SLE urine, of which 17 were ELISA validated in independent cohorts. Urine Angptl4 (area under the curve (AUC)=0.96), L-selectin (AUC=0.86), TPP1 (AUC=0.84), transforming growth factor-β1 (TGFβ1) (AUC=0.78), thrombospondin-1 (AUC=0.73), FOLR2 (AUC=0.72), platelet-derived growth factor receptor-β (AUC=0.67) and PRX2 (AUC=0.65) distinguished AR from ANR SLE, outperforming anti-dsDNA, C3 and C4, in terms of specificity, sensitivity and positive predictive value. In multivariate regression analysis, urine Angptl4, L-selectin, TPP1 and TGFβ1 were highly associated with disease activity, even after correction for demographic variables. In SLE patients with serial follow-up, urine L-selectin (followed by urine Angptl4 and TGFβ1) were best at tracking concurrent or pending disease flares. Importantly, several proteins elevated in LN urine were also expressed within the kidneys in LN, either within resident renal cells or infiltrating immune cells, based on single-cell RNA sequencing analysis. <h3>Conclusion</h3> Unbiased planar array screening of 1000 proteins has led to the discovery of urine Angptl4, L-selectin and TGFβ1 as potential biomarker candidates for tracking disease activity in LN.