tbuckley/cabot-search huggingface dataset:
Predicting the severity of joint damage in rheumatoid arthritis; the contribution of genetic factors
Authors: Hanna W van Steenbergen, Roula Tsonaka, Tom WJ Huizinga, Saskia le Cessie, Annette HM van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2014)

The severity of radiologic progression is variable between rheumatoid arthritis (RA) patients. Recently, several genetic severity variants have been identified and were replicated, these belong to 12 loci. This study determined the contribution of the identified genetic factors to the explained variance in radiologic progression and whether genetic factors, in addition to traditional risk factors, improve the accuracy of predicting the severity of radiologic progression.426 early RA patients with yearly radiologic follow-up were studied. The main outcome measure was the progression in Sharp-van der Heijde score (SHS) over 6 years, assessed as continuous outcome or categorised in no/little, moderate or severe progression. Assessed were improved fit of a linear mixed model analysis on serial radiographs, R(2) using linear regression analyses, C-statistic and the net proportion of patients that was additionally correctly classified when adding genetic risk factors to a model consisting of traditional risk factors.The genetic factors together explained 12-18%. When added to a model including traditional factors and treatment effects, the genetic factors additionally explained 3-7% of the variance (p value R(2)change=0.056). The percentage of patients that was correctly classified increased from 56% to 62%; the net proportion of correct reclassifications 6% (95% CI 3 to 10%). The C-statistic increased from 0.78 to 0.82. Sensitivity analyses using imputation of missing radiographs yielded comparable results.Genetic risk factors together explained 12-18% of the variance in radiologic progression. Adding genetic factors improved the predictive accuracy, but 38% of the patients were still incorrectly classified, limiting the value for use in clinical practice.
Evaluating the Potential Benefit of Interferon Treatment in Multiple Sclerosis
Authors: Tobias Derfuss, Ludwig Kappos
Journal: JAMA (2012)

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 Publications 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
Vascular chymase: pathophysiological role and therapeutic potential of inhibition
Authors: S Doggrell
Journal: Cardiovascular Research (2003)

Chymase is a chymotrypsin-like serine protease secreted from mast cells. Mammalian chymases are classified into two subgroups (alpha and beta) according to structure and substrate specificity; human chymase is an alpha-chymase. An important action of chymase is the ACE-independent conversion of Ang I to Ang II, but chymase also degrades the extracellular matrix, activates TGF-beta1 and IL-1beta, forms 31-amino acid endothelins and is involved in lipid metabolism. Under physiological conditions, the role of chymase in blood vessels is uncertain. In pathological situations, however, chymase may be important. In animal models of hypertension and atherosclerosis, chymase may be involved in lipid deposition and intimal and smooth muscle hyperplasia, at least in some vessels. In addition, chymase has pro-angiogenic properties. In human diseased blood vessels (e.g. atherosclerotic and aneurysmal aorta; remodeled pulmonary blood vessels), there are increases in chymase-containing mast cells and/or in chymase-dependent conversion of Ang I to Ang II. These findings have raised the possibility that inhibition of chymase may have a role in the therapy of vascular disease. The effects of chymase can theoretically be attenuated either by reducing availability of the enzyme, with a mast cell stabiliser, or alternatively with specific chymase inhibitors. The mast cell stabiliser, tranilast, was shown to be beneficial in animal models of atherosclerosis, where a prevention protocol was used, but was not effective in clinical trials where it was administered after angioplasty. Chymase inhibitors could have the advantage of being effective even if used after injury. Several orally active inhibitors, including SUN-C8257, BCEAB, NK3201 and TEI-E548, are now available. These have yet to be tested in humans, but promising results have been obtained in animal models of atherosclerosis and angiogenesis. It is concluded that orally active inhibitors of chymase may have a place in the treatment of vascular diseases where injury-induced mast cell degranulation contributes to the pathology.
Regulatory T-cell Response to Enterotoxigenic <i>Bacteroides fragilis</i> Colonization Triggers IL17-Dependent Colon Carcinogenesis
Authors: Abby L. Geis, Hongni Fan, Xinqun Wu, Shaoguang Wu, David L. Huso, Jaime L. Wolfe, Cynthia L. Sears, Drew M. Pardoll, Franck Housseau
Journal: Cancer Discovery (2015)

Many epithelial cancers are associated with chronic inflammation. However, the features of inflammation that are procarcinogenic are not fully understood. Regulatory T cells (Treg) typically restrain overt inflammatory responses and maintain intestinal immune homeostasis. Their immune-suppressive activity can inhibit inflammation-associated cancers. Paradoxically, we show that colonic Tregs initiate IL17-mediated carcinogenesis in multiple intestinal neoplasia mice colonized with the human symbiote enterotoxigenic Bacteroides fragilis (ETBF). Depletion of Tregs in ETBF-colonized C57BL/6 FOXP3(DTR) mice enhanced colitis but diminished tumorigenesis associated with shifting of mucosal cytokine profile from IL17 to IFNγ; inhibition of ETBF-induced colon tumorigenesis was dependent on reduced IL17 inflammation and was independent of IFNγ. Treg enhancement of IL17 production is cell-extrinsic. IL2 blockade restored Th17 responses and tumor formation in Treg-depleted animals. Our findings demonstrate that Tregs limit the availability of IL2 in the local microenvironment, allowing the Th17 development necessary to promote ETBF-triggered neoplasia, and thus unveil a new mechanism whereby Treg responses to intestinal bacterial infection can promote tumorigenesis.Tregs promote an oncogenic immune response to a common human symbiote associated with inflammatory bowel disease and colorectal cancer. Our data define mechanisms by which mucosal Tregs, despite suppressing excessive inflammation, promote the earliest stages of immune procarcinogenesis via enhancement of IL17 production at the expense of IFNγ production.
Retrospective and prospective studies of hepatitis B virus reactivation in malignant lymphoma with occult HBV carrier
Authors: N. Fukushima, T. Mizuta, M. Tanaka, M. Yokoo, M. Ide, T. Hisatomi, N. Kuwahara, R. Tomimasu, N. Tsuneyoshi, N. Funai, E. Sueoka
Journal: Annals of Oncology (2009)
Reversal of the Multidrug-Resistant Phenotype of Chinese Hamster Ovary Cells by L-Histidinol
Authors: R. C. Warrington, W. D. Fang
Journal: JNCI Journal of the National Cancer Institute (1989)

The amino acid analogue L-histidinol reverses the multidrug-resistance (MDR) attribute of the colchicine-resistant (CHR) variant CHRC5, a Chinese hamster ovary cell line that overexpresses a plasma membrane-associated glyco-protein and is resistant to colchicine (CH), daunorubicin, and vinblastine sulfate (VS). The level of cell kill achieved in CHRC5 cells by combinations of L-histidinol and either daunorubicin or CH approached that achieved in AUXB1 parent cells by these two drugs, whereas L-histodinol-VS combinations killed even more CHRC5 cells than VS in the parental line. The capacity of L-histidinol to reverse the MDR phenotype of the CHRC5 line was time and dose dependent and was eliminated by the addition of a twofold molar excess of L-histidine. The reversal of the MDR trait by L-histidinol appears to be independent of the drug uptake mechanism.
Prolonged repeated vaccine immuno-chemotherapy induces long-term clinical responses and survival for advanced metastatic melanoma
Authors: Brendon J Coventry, Carrie A Lilly, Peter Hersey, Antonio Michele, Richard J Bright
Journal: Journal for ImmunoTherapy of Cancer (2014)

Repetitive long-term Vaccinia Melanoma Cell Lysate (VMCL) vaccination schedules have proved clinically effective in producing Complete Responses and strong durable survivals for up to 6.1 years in a previous study of patients with advanced Stage IV and Stage IIIc melanoma. These studies were expanded to include 54 patients for further evaluation of these findings.54 patients comprising 48 Stage IV (6 M1a, 14 M1b, 28 M1c) and 6 advanced Stage III (5 IIIc; 1 IIIb) were studied using repeated intra-dermal VMCL vaccine therapy. If disease progressed, vaccine was continued together with standard chemotherapy (DTIC and/or Fotemustine). Overall survival was the primary end-point assessed, with clinical responses and toxicity recorded.From vaccine commencement, median overall survival was 14 months, ranging from 4 to 121 months. Kaplan-Meier survival analysis demonstrated overall 1, 2 and 3-year survival estimates of 57%, 26% and 18.5% respectively, and overall 5-year survival of 15.4%. No appreciable toxicity was observed. Complete Responses (CR) occurred in 16.7% (9) and partial responses (PR) in 14.8% (8) of patients. Stable disease was noted in a further 25 patients (46.3%). No response to therapy was apparent in 12 patients (22.2%). The overall response rate was 31.5% (CR + PR), with clinically significant responses (CR + PR + SD) in 77.8% of patients. Strong, durable clinical responses with overall survivals ≥ 23 months occurred in 29.6% of patients treated with repeated VMCL vaccine for advanced melanoma, (+/- concurrent chemotherapy).Prolonged, repetitive VMCL vaccination immunotherapy appears to be a clinically effective means of generating relatively high CR rates, useful clinical responses and long-term survivals, with little toxicity, but remains notably under-explored. Successive immunomodulation might explain the results. Closer analysis of repetitive dosing is required to improve clinical response rates and survival, perhaps by optimising the timing of immunotherapy delivery.Australian and New Zealand Clinical Trials Registry ANZCTRN12605000425695.
Low-dose subcutaneous alemtuzumab in refractory chronic lymphocytic leukaemia (CLL): results of a prospective, single-arm multicentre study
Authors: A Cortelezzi, M C Pasquini, A Gardellini, U Gianelli, A Bossi, G Reda, B Sarina, P Musto, W Barcellini, A Neri, G L Deliliers
Journal: Leukemia (2009)
Suppressor cell-mediated neutropenia in Felty's syndrome.
Authors: N I Abdou, C NaPombejara, L Balentine, N L Abdou
Journal: Journal of Clinical Investigation (1978)

The mechanism of neutropenia in Felty's Syndrome (FS) was tested. The suppressor capacity of mononuclear cells from patients with FS on normal bone marrow granulopoiesis was tested by the in vitro colony forming unit in culture assay. Peripheral blood, bone marrow, and spleen cells from FS patients with marked neutropenia (less than 1,000 neutrophils/mm3) suppressed the colony forming unit in culture of normal bone marrow. Cells from rheumatoid arthritis patients without neutropenia, cells from patients with drug-induced neutropenia without rheumatoid arthritis, or plasma from FS patients failed to suppress the colony forming unit in culture. Though suppressor cells were predominantly thymus-derived (T) cells, monocytes were also effective in suppression. The suppressor efficiency of cells from the various compartments were spleen greater than bone marrow greater than peripheral blood. Splenectomy in FS transiently corrected the neutropenia and eliminated suppressor cell activity. Hyperactive suppressor cells may be responsible for the neutropenia in some patients with FS. Correction of neutropenia in these patients should be directed at modulating the suppressor cell subpopulation.
Treatment of recurrent gastrointestinal haemorrhage in a patient with von Willebrand's disease with octreotide LAR and propranolol
Authors: N Krikis
Journal: Gut (2004)

Von Willebrand’ s disease (vWD) is the most common inherited bleeding disorder and is caused by quantitative deficiency or qualitative abnormalities of von Willebrand factor (vWF). Until recently, treatment of bleeding from the gastrointestinal tract in patients with vWD included administration of tranexamic acid or clotting factor products such as fresh frozen plasma, cryoprecipitate, purified vWF concentrates, or preparations that contain vWF and factor VIII. Desmopressin, beta blocking drugs, and hormonal therapy with oestrogen with or without progesterone have also been used.1,2

We report a patient with vWD who had suffered recurrent and life threatening bleeding from the gastrointestinal tract in whom, despite an extensive investigation, no apparent cause of haemorrhage was identified. He was successfully treated with combined administration of octreotide LAR (long active released) and propranolol. This is the first report on the use of octreotide LAR in a patient with vWD.

A …
Initial Psychologic Responses of Parents to the Diagnosis of Insulin-dependent Diabetes Mellitus in Their Children
Authors: Maria Kovacs, Richard Finkelstein, Terry L Feinberg, Mary Crouse-Novak, Stana Paulauskas, Myrna Pollock
Journal: Diabetes Care (1985)

As part of a prospective, longitudinal study of school-aged children with newly diagnosed insulin-dependent diabetes mellitus (IDDM), we examined how the parents adjusted to the illness. The present article documents this process for the first year of IDDM. We found no support for earlier claims that most parents resort to blatantly neurotic or psychopathologic behavior to cope. Instead, the initial strain of living with IDDM generally elicited mild and subclinical depression, anxiety, and overall distress. Mothers were more affected than fathers: they were more symptomatic (about one of four developed a mild grief reaction) and the bulk of them worried considerably about their children. However, the parents' initial emotional upheaval resolved in approximately equal to 6 mo; most mothers came to terms with IDDM by the end of the first year; and other areas of parental functioning (e.g., quality of their marriage) were not affected. Therefore, along with our previous report on how the children coped initially, the findings document the emotional resiliency of families during the first year of IDDM.
Treatment of Advanced Non–Small-Cell Lung Cancer in the Elderly: From Best Supportive Care to the Combination of Platin-Based Chemotherapy and Targeted Therapies
Authors: Cesare Gridelli
Journal: Journal of Clinical Oncology (2007)

Lung cancer in elderly patients is an increasingly common problem for the oncology practitioner. Because most patients with non–small-cell lung cancer (NSCLC) have advanced disease at diagnosis, chemotherapy is the mainstay of management. Elderly patients often present with medical and physiological characteristics that make the selection of their optimal treatment more challenging. Unfortunately, as a result, these patients are at risk of being undertreated and being included in clinical trials only rarely. Moreover, many of these patients have preexisting comorbid conditions that, independently of cancer-related symptoms, may adversely affect organ function and influence functional status. Furthermore, comorbidities often require treatment with multiple drugs, which may interfere with cancer treatment or its toxicity profile.
Adenoid cystic carcinoma of the oesophagus.
Authors: J P O'Sullivan, J S Cockburn, C E Drew
Journal: Thorax (1975)

A case of adenoid cystic carcinoma of the oesophagus occurring in a patient who had previously been treated for craniopharyngioma is presented. This is the thirteenth reported case of adenoid cystic carcinoma of the oesophagus and the first in association with craniopharyngioma. The previously described cases of oesophageal adenoid cystic carcinoma are critically reviewed, and it is suggested that this tumour is in general highly malignant and may not be so rare as is generally thought.
Carotid Stiffness Is Associated With Incident Stroke
Authors: Thomas T. van Sloten, Sanaz Sedaghat, Stéphane Laurent, Gérard M. London, Bruno Pannier, M. Arfan Ikram, Maryam Kavousi, Francesco Mattace-Raso, Oscar H. Franco, Pierre Boutouyrie, Coen D.A. Stehouwer
Journal: Journal of the American College of Cardiology (2015)
Improved Targeting of Pancreatic Cancer
Authors: Thomas M. Cardillo, Habibe Karacay, David M. Goldenberg, Dion Yeldell, Chien-Hsing Chang, David E. Modrak, Robert M. Sharkey, David V. Gold
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The early detection and diagnosis of pancreatic cancer remains a major clinical challenge in which imaging procedures have a central role. The purpose of this study was to evaluate a pretargeting method with a bispecific PAM4 (bsPAM4; anti-MUC1) antibody for radioimmunoscintigraphy of experimental human pancreatic cancer. Experimental Design: A bispecific F(ab′)2 antibody was generated from chimeric PAM4 Fab′ and murine 734 (anti-indium-diethylenetriaminepentaacetic acid) Fab′ fragments and then used in conjunction with 2 peptide haptens (111In-IMP-156 and 99mTc-IMP-192). Biodistribution studies and radioimmunoscintigraphic imaging properties of the radiolabeled bsPAM4, and pretargeted, radiolabeled peptides were examined in the CaPan1 human pancreatic tumor grown as s.c. xenografts in athymic nude mice. Tumor uptake and tumor:nontumor ratios were compared with a nontargeting irrelevant anti-CD20, bispecific rituximab, radiolabeled peptides alone, and with directly labeled PAM4. Results: Biodistribution results indicated significantly greater tumor uptake of radiolabeled peptides at 3 h after injection when pretargeting was performed with bsPAM4 as compared with the bispecific rituximab [20.2 ± 5.5 percentage of injected dose per gram of tissue (%ID/g) versus 0.9 ± 0.1%ID/g, respectively, for 111In-IMP-156, and 16.8 ± 4.8%ID/g versus 1.1 ± 0.2%ID/g, respectively, for 99mTc-IMP-192]. Similar results were obtained at the 24-h time point. Tumor:nontumor ratios were &amp;gt;30 for all of the tissues except the kidneys, where a ratio of 7.8 ± 2.8 was observed. By immunoscintigraphy, tumors could be visualized as early as 30 min after injection of the radiolabeled peptide. Conclusions: These studies demonstrate the feasibility of using the pretargeted, bispecific antibody technology for nuclear imaging of pancreatic cancer. The advantage of pretargeted bsPAM4 antibody as an imaging platform is the high specificity for pancreatic cancer as compared with the physicochemical parameters identified by current imaging technologies.
Comparison of labial and sublingual salivary gland biopsies in the diagnosis of Sjogren's syndrome.
Authors: Y L Pennec, J P Leroy, J Jouquan, A Lelong, P Katsikis, P Youinou
Journal: Annals of the Rheumatic Diseases (1990)

This study was designed to compare labial and sublingual salivary gland biopsies in the diagnosis of Sjögren9s syndrome (SS). Fourteen labial and 29 sublingual specimens were considered positive. There was a better correlation between infiltration of the ductal structure and the focus score in the sublingual salivary gland biopsy than in the labial salivary gland biopsy. Use of sublingual salivary gland biopsy as an additional diagnostic tool in SS is therefore suggested.
Risk-Reducing Salpingo-Oophorectomy in <i>BRCA</i> Mutation Carriers: Role of Serial Sectioning in the Detection of Occult Malignancy
Authors: C. Bethan Powell, Eric Kenley, Lee-may Chen, Beth Crawford, Jane McLennan, Charles Zaloudek, Miriam Komaromy, Mary Beattie, John Ziegler
Journal: Journal of Clinical Oncology (2004)

Women who carry deleterious mutations of BRCA1 or BRCA2 genes have up to a 54% lifetime risk of developing ovarian cancer. After childbearing, women at high risk increasingly choose bilateral risk-reducing salpingo-oophorectomy (RRSO). Two recent studies of BRCA mutation carriers reported occult malignancy in 2.5% of women undergoing RRSO. This study aimed to increase this detection rate using a protocol.In 1996, the University of California San Francisco Gynecologic Oncology Program instituted a surgical-pathologic RRSO protocol that was composed of complete removal and serial sectioning of both ovaries and fallopian tubes, peritoneal and omental biopsies, and collection of peritoneal washings for cytology. We report the pathologic findings in 67 BRCA mutation carriers according to the degree of adherence to this protocol.Of the 67 procedures, the protocol was followed completely or partially in 41 (61%). Seven occult malignancies were discovered, four in the fallopian tube and three in the ovaries. Six of these were microscopic, and all seven (17%) were found in specimens from complete or partial protocol procedures as opposed to standard procedures (P = .026). Other variables such as age, parity, BRCA1 or BRCA2 mutation, or type of surgery did not alter the strong effect of protocol procedure on the cancer detection rate.A rigorous operative and pathologic protocol for RRSO increases the detection rate of occult ovarian malignancy in BRCA mutation carriers nearly seven-fold. If confirmed, this finding will alter postoperative management because additional staging, chemotherapy, and follow-up may be necessary in affected women.