tbuckley/cabot-search huggingface dataset:
Nonathymulin in rheumatoid arthritis: two double blind, placebo controlled trials.
Authors: B Amor, M Dougados, C Mery, M Dardenne, J F Bach
Journal: Annals of the Rheumatic Diseases (1987)

Two randomised double blind, placebo controlled trials have been carried out to assess the effectiveness of nonathymulin, a synthetic thymic peptide hormone, in the treatment of rheumatoid arthritis (RA) and to compare three different dosage schedules (1, 5, and 10 mg/day). Nonathymulin 5 mg proved to be the most efficient dose, providing significant clinical improvement as evaluated by the global assessment of all patients who entered the trials (56% v 17% in the placebo group) (p less than 0.02) and by four objective parameters. This effect was accompanied with minimal adverse effects and was not associated with clear changes in immunological parameters. A significant correlation was observed, however, in clinical response to nonathymulin, and T cell subset imbalance was assessed using monoclonal anti-T cell antibodies and a functional suppressor T cell assay.
Common characteristics of upper and lower airways in rhinitis and asthma: ARIA update, in collaboration with GA<sup>2</sup>LEN
Authors: A. A. Cruz, T. Popov, R. Pawankar, I. Annesi‐Maesano, W. Fokkens, J. Kemp, K. Ohta, D. Price, J. Bousquet
Journal: Allergy (2007)

This update aimed to review the new evidence available to support or refute prior Allergic Rhinitis and its Impact on Asthma (ARIA) statements. A Medline search of publications between 2000 and 2005 was conducted, with articles selected by experts. New evidence supports previous ARIA statements, such as: (i) allergic rhinitis (AR) is a risk factor for asthma; (ii) patients with persistent rhinitis should be evaluated for asthma; (iii) most patients with asthma have rhinitis; (iv) a combined strategy should be used to treat the airways and (v) in low‐ to middle‐income countries, a different strategy may be needed. The increased risk of asthma has also been found among sufferers from non‐AR. Recent reports show AR is a global problem. Many studies demonstrated parallel increasing prevalence of asthma and rhinitis, but in regions of highest prevalence, it may be reaching a plateau. Factors associated with a reduced risk of asthma and AR have been identified, confirming previous findings of protection related to exposure to infections. Treatment of rhinitis with intranasal glucocorticosteroids, antihistamines, leukotriene antagonists or immunotherapy may reduce morbidity because of asthma. To take advantage of the paradigm of unified airways, there is a need to rationalize diagnosis and treatment to optimize management.
NMR spectroscopy metabolomic profiling of exhaled breath condensate in patients with stable and unstable cystic fibrosis
Authors: Paolo Montuschi, Debora Paris, Dominique Melck, Vincenzina Lucidi, Giovanni Ciabattoni, Valeria Raia, Cecilia Calabrese, Andrew Bush, Peter J Barnes, Andrea Motta
Journal: Thorax (2011)

<h3>Background</h3> Metabolomics could provide new insights into the pathophysiology of cystic fibrosis (CF) by identifying profiles of endogenous metabolites. <h3>Objectives</h3> To investigate whether metabolomics of exhaled breath condensate could discriminate between patients with unstable CF, stable CF and healthy subjects, and whether selected metabolites were responsible for between-group differences. <h3>Methods</h3> Twenty-nine patients with stable CF, 24 with unstable CF and 31 healthy subjects (age 9–24 years) participated in a cross-sectional study. Metabolomics was performed with high-resolution nuclear magnetic resonance spectroscopy. Partial least squares-discriminant analysis was used as classifier. The results were validated in a second independent study. <h3>Results</h3> Intraclass correlation coefficients for between-day and technical repeatability were 0.93 and 0.96, respectively. Bland–Altman analysis showed good within-day repeatability. Correct classification rate of CF (n=53) vs healthy subjects (n=31) was 96% (R<sup>2</sup>=0.84; Q<sup>2</sup>=0.79). Model validation with a testing sample set obtained from subjects not included in the primary analysis (23 CF and 25 healthy subjects) showed a sensitivity of 91% and a specificity of 96%. The classification rate of stable CF (n=29) vs unstable CF patients (n=24) was 95% (R<sup>2</sup>=0.82; Q<sup>2</sup>=0.78). Model external validation in 14 patients with stable CF and 16 with unstable CF showed a sensitivity of 86% and a specificity of 94%. Ethanol, acetate, 2-propanol and acetone were most discriminant between patients with CF and healthy subjects, whereas acetate, ethanol, 2-propanol and methanol were the most important metabolites for discriminating between patients with stable and unstable CF. <h3>Conclusions</h3> Nuclear magnetic resonance spectroscopy of exhaled breath condensate is reproducible, discriminates patients with CF from healthy subjects and patients with unstable CF from those with stable CF, and identifies the metabolites responsible for between-group differences.
Detection of Experimental Autoimmune Myocarditis in Rats by <sup>111</sup> In Monoclonal Antibody Specific for Tenascin-C
Authors: Mikio Sato, Tetsuya Toyozaki, Kenichi Odaka, Tomoya Uehara, Yasushi Arano, Hiroshi Hasegawa, Katsuya Yoshida, Kyoko Imanaka-Yoshida, Toshimichi Yoshida, Michiaki Hiroe, Hiroyuki Tadokoro, Toshiaki Irie, Shuji Tanada, Issei Komuro
Journal: Circulation (2002)

Although the identification of inflammatory infiltrates in endomyocardial biopsy specimens is necessary for the definite diagnosis of myocarditis, the biopsy test is invasive and is not sensitive. Therefore, a new diagnostic technique for the early and noninvasive evaluation of myocarditis has been awaited. Expression of tenascin-C (TNC), one of the oligometric extracellular glycoproteins, is induced in various pathological states, including inflammation, suggesting that TNC can be a molecular marker of myocarditis.An 111In anti-TNC monoclonal antibody Fab' fragment was injected intravenously into rats with experimental autoimmune myocarditis (EAM), and the biodistribution of this radiotracer was measured. Rapid clearance of radioactivity from the blood was observed in both EAM and control rats (<1% at 6 hours after injection). Myocardial uptake of the tracer was much higher in EAM rats than in control rats (7.54-, 4.39-, and 3.51-fold at 6, 24, and 48 hours after injection, respectively). By autoradiography, high radioactivities were clearly observed in the regions indicative of inflammation in EAM rats. Single-photon emission CT imaging demonstrated the focal myocardial uptake of 111In anti-TNC Fab' in vivo.Radiolabeled anti-TNC Fab' may be useful for the noninvasive diagnosis of myocarditis.
Changing prevalence of asthma in school children: evidence for diagnostic changes in asthma in two surveys 13 yrs apart
Authors: W Nystad, P Magnus, A Gulsvik, IJ Skarpaas, KH Carlsen
Journal: European Respiratory Journal (1997)

It is still unclear whether the reported increase in the prevalence of asthma is real or due to changes in diagnostic criteria. The objectives of this study were to compare the prevalence of diagnosed asthma with the prevalence of respiratory symptoms, and to compare the association between asthma and other atopic diseases in 1981 and 1994. The study populations comprised randomly selected school classes in Oslo in 1981 (n=1,772) and 1994 (n=2,577). The main outcomes in these comparable cross-sectional studies of children, 6-16 yrs of age, were parent-reported prevalence of diagnosed asthma, respiratory symptoms, eczema and hay fever. The questionnaire was identical in 1981 and 1994. The response rates were 94% (1,674 out of 1,772) in 1981 and 85% (2,188 out of 2,577) in 1994. The lifetime prevalence of asthma increased from 3.4% in 1981 to 9.3% in 1994; odds ratio (OR) 2.9 (95% confidence interval (95% CI) 2.1-4.0) comparing 1994 to 1981. The prevalence of occasional wheezing increased from 9.0 to 10.8%; OR 1.2 (95% CI 1.0-1.5), and attacks of wheezing from 3.7 to 6.8%; OR 1.8 (95% CI 1.3-2.5). Survival analyses for 3 year birth cohorts showed that asthma was more readily diagnosed in the latest birth cohort (1985-1988). The association between asthma and other atopic diseases decreased during the period under study. The increase in diagnosed asthma and respiratory symptoms supports a true increase in asthma. However, the larger increase in diagnosed asthma than wheezing and a reduced association between asthma and other atopic diseases suggest that the increase in asthma may be explained, in part, by changes in diagnostic criteria.
Adaptive Immune Regulation in the Gut: T Cell–Dependent and T Cell–Independent IgA Synthesis
Authors: Sidonia Fagarasan, Shimpei Kawamoto, Osami Kanagawa, Keiichiro Suzuki
Journal: Annual Review of Immunology (2010)

In mammals, the gastrointestinal tract harbors an extraordinarily dense and complex community of microorganisms. The gut microbiota provide strong selective pressure to the host to evolve adaptive immune responses required for the maintenance of local and systemic homeostasis. The continuous antigenic presence in the gut imposes a dynamic remodeling of gut-associated lymphoid tissues (GALT) and the selection of multiple layered strategies for immunoglobulin (Ig) A production. The composite and dynamic gut environment also necessitates heterogeneous, versatile, and convertible T cells, capable of inhibiting (Foxp3 + T cells) or helping (T FH cells) local immune responses. In this review, we describe recent advances in our understanding of dynamic pathways that lead to IgA synthesis, in gut follicular structures and in extrafollicular sites, by T cell–dependent and T cell–independent mechanisms. We discuss the finely tuned regulatory mechanisms for IgA production and emphasize the role of mucosal IgA in the selection and maintenance of the appropriate microbial composition that is necessary for immune homeostasis.
Outpatients: a ringside view
Authors: R. Ward
Journal: BMJ (1998)

For six months I have had a ringside seat in outpatient clinics at two London hospitals. The apparently occult nature of my disorder, a paroxysmal cough, weight loss, breathlessness, mild pyrexia, and diarrhoea persisting for 10 months has invoked the multiple application of the alliterative sisters; scans, scopes, smears, and samples, so far without any unambiguous diagnostic conclusion. But I have had a good view from the other end of the speculum.

Am I a happy outpatient? By and large, yes. Without exception the medical staff, doctors, nurses, radiologists, and technicians have been caring, kind, and efficient. All my lay questions have been answered honestly and thoroughly. Nobody has called me “Pop” (I am 69) or used my first name, which is remarkable nowadays. Every procedure has been as discrete and dignified as possible and has been explained before and during the event. I cannot complain about any stinting of resources, although the …
Late cornified envelope (LCE) proteins: distinct expression patterns of LCE2 and LCE3 members suggest nonredundant roles in human epidermis and other epithelia
Authors: H. Niehues, I.M.J.J. van Vlijmen-Willems, J.G.M. Bergboer, F.F.J. Kersten, M. Narita, W.J.A.J. Hendriks, E.H. van den Bogaard, P.L.J.M. Zeeuwen, J. Schalkwijk
Journal: British Journal of Dermatology (2015)

Deletion of the late cornified envelope (LCE) proteins LCE3B and LCE3C is a strong and widely replicated psoriasis risk factor. It is amenable to biological analysis because it precludes the expression of two epidermis-specific proteins, rather than being a single-nucleotide polymorphism of uncertain significance. The biology of the 18-member LCE family of highly homologous proteins has remained largely unexplored so far.
A Randomized Phase II Feasibility Trial of BMS-275291 in Patients with Early Stage Breast Cancer
Authors: Kathy D. Miller, Thomas J. Saphner, David M. Waterhouse, T.-T. Chen, Anita Rush-Taylor, Joseph A. Sparano, Antonio C. Wolff, Melody A. Cobleigh, Susan Galbraith, George W. Sledge
Journal: Clinical Cancer Research (2004)

Abstract Purpose: This pilot trial was performed to evaluate the safety, pharmacokinetics and feasibility of incorporating BMS-275291, a matrix metalloproteinase inhibitor (MMPI), into adjuvant breast cancer therapy. Experimental Design: Patients with stage I (T1c)-IIIA breast cancer were eligible if planned adjuvant therapy consisted of either tamoxifen alone, doxorubicin + cyclophosphamide every 21 days for four cycles (AC), or AC followed by paclitaxel every 21 days for 4 cycles (AC&amp;gt;T). Patients were stratified by planned adjuvant therapy and randomized (2:1 ratio) to BMS-275291 (1200 mg/day) or matched placebo for 1 year. Results: Seventy-two patients were recruited from March 2001 to July 2002. Grade ≥ 2 musculoskeletal toxicity, generally reversible arthralgia, was reported by 36.2% of patients receiving BMS-275291 compared with 16.7% of patients receiving placebo; difference = 19.5% (95% confidence interval: -0.06, 0.44; P = NS). Two patients receiving BMS-275291 developed palpable nodules along tendons. Grade ≥ 3 rash was reported by 8.5% of patients receiving BMS-275291 compared with 4.2% of patients receiving placebo; difference = 4.3% (95% confidence interval: -0.18, 0.3; P = NS). Overall, 33% of BMS-275291 patients and 21% of placebo patients discontinued treatment due to adverse events. BMS-275291 trough levels tended to decrease over time; 9 of 47 (19%) had ≥50% of trough concentrations &amp;gt; 124 ng/ml (IC90 for matrix metalloproteinase-9). Conclusions: The pattern of arthralgia in BMS-275291-treated patients was consistent with matrix metalloproteinase inhibitor toxicity. Although the differential incidence of arthralgia did not reach statistical significance, the trial was terminated. An adjuvant trial in this patient population is not feasible.
Highly Specific Targeting of the TMPRSS2/ERG Fusion Gene Using Liposomal Nanovectors
Authors: Longjiang Shao, Ibrahim Tekedereli, Jianghua Wang, Erkan Yuca, Susan Tsang, Anil Sood, Gabriel Lopez-Berestein, Bulent Ozpolat, Michael Ittmann
Journal: Clinical Cancer Research (2012)

The TMPRSS2/ERG (T/E) fusion gene is present in half of all prostate cancer tumors. Fusion of the oncogenic ERG gene with the androgen-regulated TMPRSS2 gene promoter results in expression of fusion mRNAs in prostate cancer cells. The junction of theTMPRSS2- and ERG-derived portions of the fusion mRNA constitutes a cancer-specific target in cells containing the T/E fusion gene. Targeting the most common alternatively spliced fusion gene mRNA junctional isoforms in vivo using siRNAs in liposomal nanovectors may potentially be a novel, low-toxicity treatment for prostate cancer.We designed and optimized siRNAs targeting the two most common T/E fusion gene mRNA junctional isoforms (type III or type VI). Specificity of siRNAs was assessed by transient co-transfection in vitro. To test their ability to inhibit growth of prostate cancer cells expressing these fusion gene isoforms in vivo, specific siRNAs in liposomal nanovectors were used to treat mice bearing orthotopic or subcutaneous xenograft tumors expressing the targeted fusion isoforms.The targeting siRNAs were both potent and highly specific in vitro. In vivo they significantly inhibited tumor growth. The degree of growth inhibition was variable and was correlated with the extent of fusion gene knockdown. The growth inhibition was associated with marked inhibition of angiogenesis and, to a lesser degree, proliferation and a marked increase in apoptosis of tumor cells. No toxicity was observed.Targeting the T/E fusion junction in vivo with specific siRNAs delivered via liposomal nanovectors is a promising therapy for men with prostate cancer.
Primary follicular and marginal-zone lymphoma of the breast: clinical features, prognostic factors and outcome: a study by the International Extranodal Lymphoma Study Group
Authors: G. Martinelli, G. Ryan, J.F. Seymour, L. Nassi, S. Steffanoni, A. Alietti, L. Calabrese, G. Pruneri, L. Santoro, M. Kuper-Hommel, R. Tsang, P.L. Zinzani, A. Taghian, E. Zucca, F. Cavalli
Journal: Annals of Oncology (2009)
Insulin and Amylin Release Are Both Diminished in First-Degree Relatives of Subjects With Type 2 Diabetes
Authors: Negar G. Knowles, Melinda A. Landchild, Wilfred Y. Fujimoto, Steven E. Kahn
Journal: Diabetes Care (2002)

OBJECTIVE—To determine whether first-degree relatives of individuals with type 2 diabetes, who are at high risk of subsequently developing hyperglycemia, manifest alterations in β-cell function including an alteration in the co-release of insulin and amylin. RESEARCH DESIGN AND METHODS—In 30 first-degree relatives and 24 matched subjects with no family history of diabetes, β-cell function was measured as the intravenous glucose-induced acute insulin response (AIRg) and acute amylin response (AARg). The insulin sensitivity index (SI) was quantified and used to account for the role of insulin sensitivity to modulate β-cell function (SI × β-cell function). RESULTS—Fasting plasma glucose (5.3 ± 0.1 vs. 5.1 ± 0.1 mmol/l; means ± SEM), immunoreactive insulin (IRI) (68 ± 7 vs. 57 ± 6 pmol/l) and amylin-like immunoreactivity (ALI) (5.5 ± 0.6 vs. 4.7 ± 0.7 pmol/l) were similar in relatives and control subjects, respectively. Relatives were insulin resistant compared with control subjects (SI: 4.86 ± 0.63 vs. 7.20 ± 0.78 × 10−5 min−1 · pmol−1 · l−1, P = 0.01), but their AIRg (392 ± 59 vs. 386 ± 50 pmol/l) and AARg (5.9 ± 0.9 vs. 6.1 ± 0.8 pmol/l) did not differ. When β-cell function was determined relative to insulin sensitivity, in the first-degree relatives, both AIRg (SI × AIRg: 1.60 ± 0.23 vs. 2.44 ± 0.31 × 10−2 min−1, P &amp;lt; 0.05) and AARg (SI × AARg: 2.39 ± 0.35 vs. 4.06 ± 0.56 × 10−4 min−1, P &amp;lt; 0.05) were reduced. The molar proportion of ALI to IRI was not altered in high-risk subjects (1.75 ± 0.16 vs. 1.71 ± 0.15%). CONCLUSIONS—First-degree relatives of subjects with type 2 diabetes have diminished β-cell function at a time when they are not hyperglycemic, and this reduction affects insulin and amylin responses proportionally. Thus, an altered amylin-to-insulin ratio is not likely to identify individuals at high risk of developing type 2 diabetes.
Successful single-cycle rituximab treatment in a patient with pemphigus vulgaris and squamous cell carcinoma of the tongue and IgG antibodies to desmocollins
Authors: Jaehwan Kim, Kwesi Teye, Hiroshi Koga, Sue-Ching Yeoh, Denis Wakefield, Takashi Hashimoto, Dedee F. Murrell
Journal: Journal of the American Academy of Dermatology (2013)
Premenstrual Symptoms and Perimenopausal Depression
Authors: Misty Richards, David R. Rubinow, Robert C. Daly, Peter J. Schmidt
Journal: American Journal of Psychiatry (2006)

OBJECTIVE: The role of ovarian steroids in both premenstrual dysphoria and perimenopausal depression has led to the suggestion that these conditions represent expressions of the same underlying disorder. Premenstrual mood symptoms were evaluated in women with perimenopause-related depression. METHOD: Self-reports and daily symptom ratings during one menstrual cycle were examined in 70 depressed perimenopausal women attending a menopause clinic and 35 nondepressed perimenopausal women. RESULTS: Twenty-six percent of the depressed and 9% of the nondepressed women reported premenstrual symptoms. Thirty-one percent of the depressed and 20% of the nondepressed women met criteria for significant menses-related symptom cyclicity (at least a 30% increase in the average ratings of at least two of four measured negative mood symptoms in the premenstrual versus the postmenstrual week); 5 of these depressed women and none of the comparison subjects described premenstrual symptoms on self-reports. Finally, 21% of the depressed and 3% of the nondepressed women met criteria for premenstrual dysphoria (symptom cyclicity and at least moderate severity, with symptoms exceeding a minimum luteal symptom severity threshold of 2.5). CONCLUSIONS: A higher-than-expected rate of menses-related symptom cyclicity and premenstrual dysphoria was observed in perimenopausal depressed women. However, neither menses-related symptom cyclicity nor premenstrual dysphoria was an invariant accompaniment of perimenopausal depression. Additionally, the rate of premenstrual dysphoria was not predicted by initial self-reports.
Propagation of Human Spermatogonial Stem Cells In Vitro
Authors: Hooman Sadri-Ardekani, Sefika C Mizrak, Saskia K M van Daalen, Cindy M Korver, Hermien L Roepers-Gajadien, Morteza Koruji, Suzanne Hovingh, Theo M de Reijke, Jean J M C H de la Rosette, Fulco van der Veen, Dirk G de Rooij, Sjoerd Repping, Ans M M van Pelt
Journal: JAMA (2009)

Young boys treated with high-dose chemotherapy are often confronted with infertility once they reach adulthood. Cryopreserving testicular tissue before chemotherapy and autotransplantation of spermatogonial stem cells at a later stage could theoretically allow for restoration of fertility.To establish in vitro propagation of human spermatogonial stem cells from small testicular biopsies to obtain an adequate number of cells for successful transplantation.Study performed from April 2007 to July 2009 using testis material donated by 6 adult men who underwent orchidectomy as part of prostate cancer treatment. Testicular cells were isolated and cultured in supplemented StemPro medium; germline stem cell clusters that arose were subcultured on human placental laminin-coated dishes in the same medium. Presence of spermatogonia was determined by reverse transcriptase polymerase chain reaction and immunofluorescence for spermatogonial markers. To test for the presence of functional spermatogonial stem cells in culture, xenotransplantation to testes of immunodeficient mice was performed, and migrated human spermatogonial stem cells after transplantation were detected by COT-1 fluorescence in situ hybridization. The number of colonized spermatogonial stem cells transplanted at early and later points during culture were counted to determine propagation.Propagation of spermatogonial stem cells over time.Testicular cells could be cultured and propagated up to 15 weeks. Germline stem cell clusters arose in the testicular cell cultures from all 6 men and could be subcultured and propagated up to 28 weeks. Expression of spermatogonial markers on both the RNA and protein level was maintained throughout the entire culture period. In 4 of 6 men, xenotransplantation to mice demonstrated the presence of functional spermatogonial stem cells, even after prolonged in vitro culture. Spermatogonial stem cell numbers increased 53-fold within 19 days in the testicular cell culture and increased 18,450-fold within 64 days in the germline stem cell subculture.Long-term culture and propagation of human spermatogonial stem cells in vitro is achievable.