tbuckley/cabot-search huggingface dataset:
Use of a Combination of Approaches to Identify and Validate Relevant Tumor-Associated Antigens and Their Corresponding Autoantibodies in Ovarian Cancer Patients
Authors: Audrey Gagnon, Jae-Hoon Kim, John O. Schorge, Bin Ye, Brian Liu, Kathleen Hasselblatt, William R. Welch, Christina A. Bandera, Samuel C. Mok
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Novel biomarkers are urgently needed to increase the sensitivity of CA125 for the early detection of ovarian cancer. Indeed, it has been shown that as much as 20% of early-stage patients do not express significant levels of this biomarker. Therefore, the possibility of using autoantibodies directed against tumor-associated antigens as putative cancer markers is being more examined. Indeed, many autoantibodies have recently been shown to correlate with cancer patient prognosis or to be suitable for detection of the disease. Experimental Design: In this study, we have used a new approach involving the use of proteomics, immunology, and ELISA methods to identify relevant autoantibodies in the plasma of ovarian cancer patients. To do so, we developed an innovative technique called two-dimensional differential gel electrophoresis analysis of immunoprecipitated tumor antigens. Results: This strategy allowed us to successfully identify novel circulating autoantibodies directed against the S100A7 protein in the plasma of ovarian cancer patients. Further real-time reverse transcription-PCR and immunohistochemical studies confirmed that the S100A7 mRNA and protein were highly expressed in ovarian tumors but absent in normal and benign tissues. Moreover, a preliminary study involving 138 patients confirmed that the plasma levels of anti-S100A7 antibodies are significantly elevated in early- and late-stage ovarian cancer patients compared with healthy controls and with patients with benign gynecologic diseases. Conclusions: This shows that our approach is a valuable tool to successfully identify autoantibodies and tumor-associated antigens in cancer patients and that future research assessing their putative clinical usefulness would be worthwhile.
Defining TNF -, IFN - and IFN -induced gene expression profiles in human monocytes to estimate their cytokine-specific impact in inflammatory diseases
Authors: B. Smiljanovic, J. R. Grun, T. Haupl, A. Radbruch, A. Grutzkau
Journal: Annals of the Rheumatic Diseases (2010)

Cytokines contribute to the host defence by an overall tuning of the immune system. Nevertheless, an excessive and uncontrolled production of proinflammatory cytokines can be responsible for the onset and maintenance of chronic inflammatory diseases like systemic lupus erythematosus (SLE). The cytokine production that accompanies pathophysiological processes of chronic inflammation is reflected within the monocyte transcriptome. The present study was designed to define stimulus-specific expression patterns in tumour necrosis factor α (TNFα), interferon type I (IFNγ) and …
A recurrent glycine substitution mutation, G2043R, in the type VII collagen gene (COL7A1) in dominant dystrophic epidermolysis bullosa
Authors: None Mellerio, None Salas-Alanis, None Talamantes, None Horn, None Tidman, None Ashton, None Eady, None Mcgrath
Journal: British Journal of Dermatology (1998)

Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the type VII collagen gene (COL7A1). Nearly all cases of dominant DEB are caused by glycine substitution mutations occurring within the triple helical region of type VII collagen, and most of the mutations are unique to individual families. In this study, we identified a patient of Hispanic‐Mexican origin with a mild form of DEB, which resulted from a de novo dominant glycine substitution, G2043R, in exon 73 of COL7A1. We also investigated a Scottish family with a three‐generation pedigree of dominant DEB, in whom the same glycine to arginine substitution mutation was demonstrated. This particular mutation has also been detected previously in three other families with dominant DEB: one Italian, one Hungarian and one Norwegian. Given the widespread geographical distribution of this mutation and the demonstration of its occurrence as a de novo event, G2043R therefore represents the first example of a mutational hotspot in dominant DEB. Interestingly, although both the Mexican and Scottish families we studied had some clinical features in keeping with the Pasini form of the disorder, there was considerable interfamilial variability as well as intrafamilial diversity in the affected individuals.
Safety and pharmacokinetics of nintedanib and pirfenidone in idiopathic pulmonary fibrosis
Authors: Takashi Ogura, Hiroyuki Taniguchi, Arata Azuma, Yoshikazu Inoue, Yasuhiro Kondoh, Yoshinori Hasegawa, Masashi Bando, Shinji Abe, Yoshiro Mochizuki, Kingo Chida, Matthias Klüglich, Tsuyoshi Fujimoto, Kotaro Okazaki, Yusuke Tadayasu, Wataru Sakamoto, Yukihiko Sugiyama
Journal: European Respiratory Journal (2014)

A randomised, double-blind, phase II, dose escalation trial was conducted to assess the safety, tolerability and pharmacokinetics of the tyrosine kinase inhibitor nintedanib, alone and when added to ongoing pirfenidone therapy, in Japanese patients with idiopathic pulmonary fibrosis. 50 Japanese patients were randomised to receive nintedanib or placebo in one of three cohorts (nintedanib 50 mg twice daily or 100 mg twice daily for 14 days, or 150 mg twice daily for 28 days). Patients receiving pirfenidone at inclusion were stratified to every nintedanib dose group and placebo. Adverse events were reported in nine out of 17 patients receiving nintedanib alone and 10 out of 21 patients receiving nintedanib added to pirfenidone. All adverse events were mild or moderate in intensity. Gastrointestinal disorders were the most common adverse event. Maximum plasma concentration and area under the curve at steady state for nintedanib and its metabolites tended to be lower when nintedanib was added to pirfenidone. Nintedanib had no effect on the pharmacokinetics of pirfenidone. In conclusion, further study is needed to evaluate the safety and tolerability profile of nintedanib when added to pirfenidone in patients with idiopathic pulmonary fibrosis. There was a trend toward lower exposure of nintedanib when it was added to pirfenidone.
Tacrolimus ointment improves psoriasis in a microplaque assay
Authors: None Remitz, None Reitamo, None Erkko, None Granlund, None Lauerma
Journal: British Journal of Dermatology (1999)

Tacrolimus (FK506) is an effective and well tolerated immunosuppressant used to prevent allograft rejection. We describe the evaluation of two tacrolimus ointment formulations for treatment of chronic plaque-type psoriasis. This was a microplaque assay with randomized, double-blind design. Sixteen patients (15 men, one woman, all white and 28-69 years old) with chronic plaque-type psoriasis participated. Six different ointments were applied to discrete microplaques, 17 mm in diameter, on a descaled psoriasis lesion: these were tacrolimus ointment with diisopropyl adipate as penetration enhancer, tacrolimus ointment without diisopropyl adipate, 0.1% betamethasone 17alpha-valerate ointment, 0.005% calcipotriol ointment and, as controls, the ointment bases for tacrolimus and betamethasone. Ointments were reapplied and the area was sealed every 2-3 days during the 14-day treatment period. After 7 and 14 days, erythema and infiltration were graded on a scale of 0-4, and superficial blood flow was measured with a laser Doppler flowmeter. Epidermal thickness was measured histologically at the end of treatment. Compared with the vehicle controls, sites treated with tacrolimus ointment (with or without penetration enhancer) showed a significant reduction in erythema and infiltration (P < 0. 001), a significant reduction in superficial blood flow (P < 0.01) and a significant decrease in epidermal thickness (P < or = 0.001). Results for betamethasone and calcipotriol, when compared with the vehicle controls, were similar. These results suggest that, under conditions of descaling and occlusion, tacrolimus ointment is effective in the treatment of psoriasis.
Extended anatomical VATS resections in patients with NSCLC
Authors: Uldis Kopeika, Thomas Krbek, Petar Traykov, Joachim Kolb, Maria-L. Mlynek-Kersjes, Kato Kambartel, Thomas Voshaar
Journal: European Respiratory Journal (2014)

Background: VATS is gaining popularity as a technique for performing anatomical resections in lung cancer patients, showing lesser pain, shorter hospital stay and lower blood loss compared to patients undergoing traditional thoracotomy.  Aim: To analyze opportunity, morbidity and mortality of extended anatomical VATS resections.  Methods: Retrospective analysis of Lung Cancer centre database.  Results: Between 2012 and 2013, 74 patients were scheduled for anatomical VATS resections. Extended resections were performed in 32 patients: bilobectomy in one, segmental resection in 23, lobectomy with chest wall resection in 4, bronchial wedge resection in 3 and intrapericardial resection in one patient. All patients were extubated in the operative room. There was no in-hospital mortality. We observed the below listed complications: chest wall empyema after chest wall reconstruction with synthetic mesh in 1 patient with severe diabetes, bronchus stump insufficiency after VATS segmentectomy in 2 cases. Bronchus stump insufficiency was successfully treated with muscle overlap plastic. Two patients, planed for VATS resection had to be converted due to: 1. massive lymph node silicosis; 2. difficulty in determining segment border.  Conclusion: extended anatomical VATS resections are feasible in selected cases with low perioperative morbidity and mortality and a short length of hospital stay. In case of VATS segmental resections patients can not only benefit from a parenchyma-saving resection, but also by the minimally invasive approach. The VATS lobectomy with chest wall resection not only allows to specify the location of the ribs cut, but also to preserve the chest wall muscles, because the rib cut is made from the thorax inside.
Precipitins and specific IgG antibody to Aspergillus fumigatus in a chest unit population.
Authors: J A Faux, D J Shale, D J Lane
Journal: Thorax (1992)

BACKGROUND: The enzyme linked immunosorbent assay (ELISA) for detecting IgG antibodies to Aspergillus fumigatus is more sensitive than the measurement of Aspergillus precipitins. The relation of the results from both techniques to the clinical pattern of disease in a large unselected group of patients from a large referral centre is unknown. METHODS: The clinical relation of precipitins to Aspergillus fumigatus to clinical disease was determined retrospectively in 98 patients attending a primary referral centre. Precipitin results were compared with the specific IgG antibody to A fumigatus in 88 of the sera. Precipitins were determined by the agar gel double diffusion test and specific IgG antibody to A fumigatus by a quantitative ELISA. RESULTS: Precipitins were detected in the unconcentrated serum of 51 patients. Thirty nine of these had a mycetoma or allergic bronchopulmonary aspergillosis, 34 having specific IgG antibody to A fumigatus more than the control range. Forty seven patients had precipitins only after threefold concentration of serum or to only one of the four A fumigatus antigen extracts. Most of these had specific IgG in or near the control range. Thirty of these had A fumigatus skin test negative asthma or bronchiectasis, in which aspergillus was probably not pathogenic. There was a close relation between the level of antibody detected by the ELISA and the number of precipitin lines. CONCLUSIONS: This study reaffirmed the supportive role of aspergillus precipitins in the diagnosis of pulmonary aspergillosis. No additional benefit in the routine use of the ELISA was seen. It also showed that care should be taken in interpreting positive precipitin results from concentrated serum and that using several rather than one A fumigatus antigen extract is helpful for identifying allergic aspergillosis.
Three-dimensional High-Frequency Ultrasound Imaging for Longitudinal Evaluation of Liver Metastases in Preclinical Models
Authors: Kevin C. Graham, Lauren A. Wirtzfeld, Lisa T. MacKenzie, Carl O. Postenka, Alan C. Groom, Ian C. MacDonald, Aaron Fenster, James C. Lacefield, Ann F. Chambers
Journal: Cancer Research (2005)

Abstract Liver metastasis is a clinically significant contributor to the mortality associated with melanoma, colon, and breast cancer. Preclinical mouse models are essential to the study of liver metastasis, yet their utility has been limited by the inability to study this dynamic process in a noninvasive and longitudinal manner. This study shows that three-dimensional high-frequency ultrasound can be used to noninvasively track the growth of liver metastases and evaluate potential chemotherapeutics in experimental liver metastasis models. Liver metastases produced by mesenteric vein injection of B16F1 (murine melanoma), PAP2 (murine H-ras–transformed fibroblast), HT-29 (human colon carcinoma), and MDA-MB-435/HAL (human breast carcinoma) cells were identified and tracked longitudinally. Tumor size and location were verified by histologic evaluation. Tumor volumes were calculated from the three-dimensional volumetric data, with individual liver metastases showing exponential growth. The importance of volumetric imaging to reduce uncertainty in tumor volume measurement was shown by comparing three-dimensional segmented volumes with volumes estimated from diameter measurements and the assumption of an ellipsoid shape. The utility of high-frequency ultrasound imaging in the evaluation of therapeutic interventions was established with a doxorubicin treatment trial. These results show that three-dimensional high-frequency ultrasound imaging may be particularly well suited for the quantitative assessment of metastatic progression and the evaluation of chemotherapeutics in preclinical liver metastasis models.
Local Injection of Hydrocortisone and Procaine in Osteo-Arthritis of the Hip Joint
Authors: V. M. Leveaux, C. E. Quin
Journal: Annals of the Rheumatic Diseases (1956)

Present InvestigationThe object of the investigation was to compare the effect of an injection of 5 ml. 2 per cent.procaine (Injection "P") with that of a combined injection of 50 mg.hydrocortisone and 5 ml. 2 per cent.procaine (Injection "H").330
The Pulmonary Vasculitides
Authors: Stephen K. Frankel, Marvin I. Schwarz
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

The pulmonary vasculitides are a rare group of heterogeneous disorders unified by the histopathologic finding of inflammation and destruction of the blood vessel wall. Diagnosis of these disorders is exceptionally challenging, given their highly variable clinical presentation, their relative rarity, and the overlap of the signs and symptoms of vasculitis with much more common entities. However, advances in the management of vasculitis allow for accurate diagnosis, risk stratification in the individual patient, and the implementation of evidence-based, effective pharmacologic therapies. This concise clinical review addresses the diagnosis and management of the patient with pulmonary vasculitis and provides an up-to-date review of the state of the field.
Phase II Study of Pentostatin in Patients With Corticosteroid-Refractory Chronic Graft-Versus-Host Disease
Authors: David A. Jacobsohn, Allen R. Chen, Marianna Zahurak, Steven Piantadosi, Viki Anders, Javier Bolaños-Meade, Meghan Higman, Jeffrey Margolis, Michele Kaup, Georgia B. Vogelsang
Journal: Journal of Clinical Oncology (2007)

Therapy for patients with chronic graft-versus-host disease (cGVHD) is based on prolonged immunosuppression with corticosteroids. There is no standard therapy for patients whose cGVHD does not resolve with corticosteroid treatment. Pentostatin, a potent inhibitor of adenosine deaminase, has activity in acute GVHD. We examined the toxicity and efficacy of pentostatin in a prospective phase II trial in corticosteroid-refractory cGVHD.Patients of any age were eligible. Patients received pentostatin 4 mg/m2 intravenously every 2 weeks for 12 doses, and continued therapy as long as benefit was documented. Corticosteroid taper was begun after three doses of pentostatin. Responses were graded in real time in the skin, mouth, and liver using objective response criteria.Fifty-eight heavily pretreated (median, four prior regimens) patients (median age, 33 years) were enrolled. Results are shown as an intent-to-treat analysis. Of the 58 patients, a total of 32 (55%; 95% CI, 42% to 68%) had an objective response, as evaluated by use of a new grading scale. Infection was the most significant toxicity, with 11 grade 3 to 4 infectious events. The survival at 1 and 2 years was 78% (95% CI, 64% to 86%) and 70% (95% CI, 57% to 80%), with cGVHD with/without infection accounting for the majority of deaths.Pentostatin has immunosuppressive effects that are currently being explored further for treatment of cGVHD.
Exhaled NO and plasma cGMP increase after endotoxin infusion in healthy volunteers
Authors: A. Soop, A. Sollevi, E. Weitzberg, J.O.N. Lundberg, J. Palm, J. Albert
Journal: European Respiratory Journal (2003)

Nitric oxide (NO) is believed to be involved in the pathophysiology of sepsis. This study evaluated the activity of the NO pathway in a human endotoxin model. At baseline and after endotoxin, on-line measurements of exhaled NO (eNO) were made using a chemiluminescence technique with a single-breath method. NO-free air was inhaled prior to exhalation against a resistance. NO in orally and nasally exhaled air and in rectal gas was investigated. Plasma nitrite, nitrate, and guanosine 3′, 5′-monophosphate (cGMP) and the events after diclophenac administration were also studied. Endotoxin infusion resulted in tachycardia and fever. An early increase in oral eNO concentration was observed and oral eNO decreased after diclophenac administration. NO exhaled nasally, NO in rectum gas and nitrite/nitrate levels remained unchanged over the study period. cGMP increased after 4 h. These findings suggest an early increase in nitric oxide production from the lungs, probably due to increased activity of the constitutive nitric oxide synthase upon endotoxin stimulation. In contrast, nitric oxide production in the upper airways, measured as nasally exhaled nitric oxide and nitric oxide in rectal gas, remained unchanged. Further studies will elucidate if exhaled nitric oxide is a valuable marker of sepsis-induced lung injury and if monitoring of treatment is possible.
Midterm Echocardiographic Follow-Up After Ross Operation
Authors: M. Briand, P. Pibarot, J. G. Dumesnil, P. Cartier
Journal: Circulation (2000)

The pulmonary autograft (Ross) operation is an attractive treatment for aortic valve disease, but hemodynamic follow-up is not well defined.One hundred thirty-two consecutive patients (62% male, mean age 40+/-11 years) were followed up to 5 years after the Ross operation. Echocardiography was performed early (within 30 days), 3 to 6 months, and yearly after surgery. The valve effective orifice area (EOA) and mean transvalvular gradient of both aortic and pulmonary valves were measured, and transvalvular regurgitation was assessed by using color Doppler echocardiography. EOA was indexed for body surface area. The hemodynamic performance was excellent for both the aortic and pulmonary valves early after surgery (gradient, 3+/-4 and 3+/-4 mm Hg, respectively). It remained stable thereafter for the aortic valve, whereas there was a significant deterioration of the EOA (-0. 74+/-0.82 cm(2)) and gradient (+6+/-8 mm Hg) for the pulmonary valve, which occurred mostly during the first 6 months after surgery. This hemodynamic deterioration resulted in suboptimal (defined as an EOA index <0.85 cm(2)/m(2)) hemodynamics in 19.3% of the patients, to the extent that 3 (2%) of the 132 patients eventually had to be subjected to further surgery for severe pulmonary valve stenosis.The pulmonary autograft provides continued excellent hemodynamics in the aortic position, whereas moderately high gradients can be found across the pulmonary homograft in some patients. Further studies are necessary to identify the factors responsible for the deterioration of the hemodynamic performance of the homograft in the pulmonary position and to determine its impact on right ventricular function and clinical status.
Heritability of Malaria in Africa
Authors: Margaret J Mackinnon, Tabitha W Mwangi, Robert W Snow, Kevin Marsh, Thomas N Williams
Journal: PLoS Medicine (2005)

Background While many individual genes have been identified that confer protection against malaria, the overall impact of host genetics on malarial risk remains unknown. Methods and Findings We have used pedigree-based genetic variance component analysis to determine the relative contributions of genetic and other factors to the variability in incidence of malaria and other infectious diseases in two cohorts of children living on the coast of Kenya. In the first, we monitored the incidence of mild clinical malaria and other febrile diseases through active surveillance of 640 children 10 y old or younger, living in 77 different households for an average of 2.7 y. In the second, we recorded hospital admissions with malaria and other infectious diseases in a birth cohort of 2,914 children for an average of 4.1 y. Mean annual incidence rates for mild and hospital-admitted malaria were 1.6 and 0.054 episodes per person per year, respectively. Twenty-four percent and 25% of the total variation in these outcomes was explained by additively acting host genes, and household explained a further 29% and 14%, respectively. The haemoglobin S gene explained only 2% of the total variation. For nonmalarial infections, additive genetics explained 39% and 13% of the variability in fevers and hospital-admitted infections, while household explained a further 9% and 30%, respectively. Conclusion Genetic and unidentified household factors each accounted for around one quarter of the total variability in malaria incidence in our study population. The genetic effect was well beyond that explained by the anticipated effects of the haemoglobinopathies alone, suggesting the existence of many protective genes, each individually resulting in small population effects. While studying these genes may well provide insights into pathogenesis and resistance in human malaria, identifying and tackling the household effects must be the more efficient route to reducing the burden of disease in malaria-endemic areas.