tbuckley/cabot-search huggingface dataset:
Polymorphisms of MDR1, ADRB2 and IL13 genes are markers of therapy-resistant bronchial asthma (BA) in Russian patients
Authors: Zhanna Mironova, Vasiliy Trofimov, Mikhail Dubina, Anna Ulitina, Elena Yanchina
Journal: European Respiratory Journal (2012)

Background. BA is multifactorial disease caused by the interaction of genes and environment. Genetic polymorphisms influence BA development, progression and severity as well as response to BA therapy.  Aim. To assess severity of BA and effectiveness of BA pharmacotherapy in patients with different genetic background.  Methods. Genomic DNA was extracted from peripheral leukocytes. We investigated 4 SNPs by PCR-RFLP in 122 BA patients and in 103 healthy controls.  Results. Distribution of genotypes was similar to other European populations, except MDR1 gene. We revealed numerous associations of genetic variants with increased risk (IR): 3435CC with IR of BA (OR=3.92, 95%CI 1.74-8.79); 3435CC with IR of GCS doses more than 20 mg of prednisolon (OR=20.89, 95%CI 5.10-85.53); 3435CC with IR of therapy-resistant BA (OR=6.12, 95%CI 2.42-15.48); 16Gly with IR of respiratory failure (OR=17.31, 95%CI 2.01-149.28); 27GluGlu with IR of therapy-resistant BA (OR=3.35, 95%CI 1.16-9.66); 130Gln with IR of therapy-resistant BA (OR=2.09, 95%CI 1.01-4.30).  Conclusion. Analysis of MDR1, ADRB2 and IL13 polymorphisms is useful for both preventive care (revealing subjects with increased predisposition to BA) and pharmacotherapy optimization due to prediction of BA severity and risk of therapy-resistant BA.
C-reactive protein in community acquired pneumonia - Correlation with main clinical indices
Authors: Pavlina Nikolova, Yavor Ivanov, Nikolay Yanev, Plamen Pavlov, Nikolay Kyuchukov, Tsanya Popova
Journal: European Respiratory Journal (2012)

Background: C-reactive protein (CRP) has a significant role as a factor, correlating with main clinical indices of the community acquired pneumonia (CAP).

Aim: To evaluate the relationship between CRP-levels and main clinical signs of CAP – severity, length of stay, complications, outcome.

Methods: Prospective study for 1 year period. 50 patients with CAP severity CURB 65 score 2-5, treated in Pulmonary Clinic were enrolled. 17 of them were women and 33 (60%) – men, average age 54,4 ± 14,6 y. Serum levels of CRP were tested at 1-st and 7-th day of hospital stay. Clinical indices such as concomitant diseases, length of stay, complications, antibiotic prescriptions, outcome have been studied.

Results: At admission the levels of CRP were increased up to 434 mg/dl, mean value 83,41 mg/dl (normal range 0-5mg/dl). Most of the patients (54%) had score 3 concerning CURB65, followed by 2 – 24% and 4 – 20%. 62% of them have had concomitant diseases, mainly cardiovascular – in 44% of the cases. The most frequent used antibiotic was ceftriaxone – in 92% of cases. 72% of the patients were treated with two antibiotics, 12% - with three. The duration of antibiotic treatment was average 7,26±1,69 d (from 5 to 12 days). The length of stay was 8,4 d (from 7 to 12 days). Significant relationship was established between CRP and: severity of CAP (CURB65) p<0,05, r=0,38; the duration of intravenous antibiotic treatment p<0,05, r=0,32; antibiotic prescription at leaving hospital day p<0,05; r=0,39; complications; length of stay p<0,05; r=0,30; outcome p<0,05; r=0,50.

Conclusion: CRP is a sensitive and reliable factor, correlating with the severity of CAP, length of stay and outcome.
Prospective study of vulvar nevi
Authors: Barbara Rock, Antoinette F. Hood, John A. Rock
Journal: Journal of the American Academy of Dermatology (1990)

We report the results of a year-long prospective study to approximate the prevalence of pigmented lesions of the vulva in a gynecology practice. A total of 301 new patients were screened during their routine gynecologic examination. Thirty-one (10.3%) had pigmented lesions in the vulvar region, and an additional six (2%) had diffuse hyperpigmentation. Only seven patients (2.3%) had vulvar nevocytic nevi.
Psoriasis and Arthritis
Authors: V. Wright
Journal: Annals of the Rheumatic Diseases (1956)

Material and MethodsIn all, 42 patients with psoriasis and arthritis have been considered, 34 with erosive arthritis (the term "erosive arthritis" being used in preference to "rheumatoid arthritis" so that the issue may not be prejudged), six with degenerative joint disease, one with gout, and one with rheumatic fever.In all cases the diagnosis of psoriasis was confirmed by a dermatologist (Dr.D. S. Wilkinson).In five, information was incomplete, two patients having died, the other three having left the district.The others were examined personally, their serum was submitted to certain laboratory tests, and radiographic studies were made.This group has been contrasted with 55 unselected patients with rheumatoid arthritis who were found to have a positive Differential Agglutination Test (Waaler-Rose), and with an unselected group of patients with psoriasis but no joint manifestations (310 patients in all).348
THE COMPLEMENT FIXATION REACTION IN MONKEY MALARIA
Authors: Lowell T. Coggeshall, Monroe D. Eaton
Journal: The Journal of Experimental Medicine (1938)

1. A specific complement fixation reaction test for Plasmodium knowlesi malaria in rhesus monkeys is reported with details involved in the preparation of the antigen and procedures employed in setting up the test. 2. It was found that specific complement-fixing antibodies appeared early in the course of the experimental disease and persisted during the course of the chronic infection. 3. The first appearance of complement-fixing antibodies was generally followed by a temporary fall in titer. During the first 2 months of infection there was no apparent relationship between the number of circulating parasites and the changes in complement fixation titer. 4. During the stage of chronic infection there was a fall in the titer of complement-fixing antibodies preceding each parasitic relapse, and after the relapse had terminated, there was an elevation of the complement-fixing titer.
Myeloid-Derived Suppressor Cells Inhibit T-Cell Activation by Depleting Cystine and Cysteine
Authors: Minu K. Srivastava, Pratima Sinha, Virginia K. Clements, Paulo Rodriguez, Suzanne Ostrand-Rosenberg
Journal: Cancer Research (2009)

Myeloid-derived suppressor cells (MDSC) are present in most cancer patients and are potent inhibitors of T-cell-mediated antitumor immunity. Their inhibitory activity is attributed to production of arginase, reactive oxygen species, inducible nitric oxide synthase, and interleukin-10. Here we show that MDSCs also block T-cell activation by sequestering cystine and limiting the availability of cysteine. Cysteine is an essential amino acid for T-cell activation because T cells lack cystathionase, which converts methionine to cysteine, and because they do not have an intact xc- transporter and therefore cannot import cystine and reduce it intracellularly to cysteine. T cells depend on antigen-presenting cells (APC), such as macrophages and dendritic cells, to export cysteine, which is imported by T cells via their ASC neutral amino acid transporter. MDSCs express the xc- transporter and import cystine; however, they do not express the ASC transporter and do not export cysteine. MDSCs compete with APC for extracellular cystine, and in the presence of MDSCs, APC release of cysteine is reduced, thereby limiting the extracellular pool of cysteine. In summary, MDSCs consume cystine and do not return cysteine to their microenvironment, thereby depriving T cells of the cysteine they require for activation and function.
Routine testing for HIV is acceptable and effective, show pilot studies
Authors: A. O'Dowd
Journal: BMJ (2011)

Patients and healthcare professionals are ready and willing to accept routine testing for HIV in areas of high prevalence of the disease, according to the Health Protection Agency.

The agency has recommended that HIV testing in high prevalence areas of England—areas where HIV prevalence is greater than two per 1000 among 15-59 year olds—should be expanded because pilots have shown it is effective, feasible, and acceptable.

The recommendation, contained in an agency report published on 20 September, is being considered by the government and could mean that for the first time in the UK, routine, “opt out” HIV tests would be offered to everyone signing up to primary care …
Contempo '81. Pediatrics: adolescent medicine
Authors: S. K. Schonberg
Journal: JAMA (1981)

The teenager must accomplish a series of crucial developmental tasks during the few short years of adolescence. During these years, illness will often interfere with the attainment of the skills and attitudes necessary to becoming a healthy and productive adult. Either physiological or behavioral dysfunction may prove an obstacle to the achievement of academic and vocational goals, the realization of independence from parental support and control, the development of adult psychosexual capability, the derivation of a healthy self-identity and feelings of self-worth, and even the completion of somatic maturation.<sup>1</sup>During the past two decades, we have reached a better understanding of both the nature and extent of those disease processes that are most likely to have impact on adolescents. <h3>Health Indices in Adolescents</h3> There are more than 40 million Americans between the ages of 10 and 19 years, accounting for approximately one fifth of our population. It is estimated
Characterization of mixed allogeneic chimeras. Immunocompetence, in vitro reactivity, and genetic specificity of tolerance.
Authors: S T Ildstad, S M Wren, J A Bluestone, S A Barbieri, D H Sachs
Journal: The Journal of Experimental Medicine (1985)

Mixed allogeneically reconstituted mice (B10 + B10.D2----B10) that specifically accept B10.D2 tail skin allografts were examined for in vivo and in vitro immunocompetence, patterns of hematopoietic repopulation, and in vitro reactivity. In vitro, mixed allogeneic chimeras (B10 + B10.D2----B10) manifested specific tolerance in mixed lymphocyte reactions and cell-mediated lympholysis to B10 and B10.D2 splenocytes, with normal responses to third-party (B10.BR) cells. Such chimeras were immunocompetent in B cell and helper T cell responses, as assessed by their primary plaque forming cell responses to in vivo sheep red blood cell immunization. This is in contrast to fully allogeneic chimeras, which responded less well. In addition, survival of the mixed allogeneic chimeras in a conventional animal facility was superior to that of fully allogeneic chimeras, and similar to syngeneically reconstituted (B10----B10) mice. Specific tolerance to skin grafts, degree of allogeneic engraftment, and persistence of chimerism was also assessed in a noncongenic mixed allogeneic combination (B10 + C3H----B10). Such animals manifested specific hyporeactivity to C3H skin allografts, but eventual chronic rejection of the grafts occurred in spite of stable and persistent mixed chimerism. MHC-congenic (B10.BR) skin grafts were accepted indefinitely in the same animals, suggesting that skin-specific non-major histocompatibility complex antigens were responsible for rejection of the C3H skin allografts.
Thoracoscopy: influence of the procedure on some respiratory and cardiac values.
Authors: P Faurschou, F Madsen, K Viskum
Journal: Thorax (1983)

In eight patients with pleural effusion arterial oxygen and carbon dioxide tensions (PaO2 and PaCO2), pH, respiratory frequency, and cardiac rhythm and frequency were measured before, during, and after thoracoscopy. Four of the patients had a PaO2 below 70 mm Hg (9.3 kPa) before the procedure. During and after the procedure respiratory frequency increased and PaCO2 fell, indicating hyperventilation, while the other indices remained unchanged. It is concluded that respiration and the circulation readily adapt to the changes produced by the pneumothorax and the manipulation during thoracoscopy.
Intravascular bronchioloalveolar tumour
Authors: S De-Luca, CM Sanguinetti, I Bearzi, B Murer
Journal: European Respiratory Journal (1990)

A case of intravascular bronchioloalveolar tumour (IVBAT) presenting in a 49 yr old asymptomatic man is reported. IVBAT was diagnosed by open lung biopsy. The disease had a presumable duration of ten years and showed a low tendency to progress. The endothelial origin of the tumour was immunohistochemically proven.
And Now a Yugoslav JAMA
Authors: Irving Thomas
Journal: JAMA (1985)

In 1918, Yugoslavia emerged as a new nation, patched together at the end of World War I from the defeated Austrian-Hungarian and Ottoman Empires plus the kingdoms of Montenegro and Serbia. For some years Yugoslavia was an independent kingdom. After World War II it became a republic. Now the official name is the Socialist Federal Republic of Yugoslavia. Throughout its history turbulence has often been the rule and not the exception. Yugoslavia controls important land routes from central and western Europe to the Aegean Sea and Turkish Straits. Since the Middle Ages and the times of the Byzantine Empire, the area has served as a natural bridge between East and West, thus being a vulnerable prize in geopolitical conflicts. Today, the economic problems of Yugoslavia are similar to those of many countries. It is encountering a high rate of inflation and substantial unemployment and is weathering balance of payment and
Non-uniform prolongation of intracellular Ca2+ transients recorded from the epicardial surface of isolated hearts from rabbits with heart failure
Authors: G Ng
Journal: Cardiovascular Research (1998)

Objectives: To study the time course of Ca2+ transients recorded from the left ventricular epicardial surface of isolated hearts from rabbits with heart failure and to correlate the results with mechanical function. Methods: Heart failure was induced in the rabbit 8 weeks after coronary ligation (n=17) with 13 controls. Echocardiography was used to assess in vivo left ventricular dysfunction. The fluorescent indicator Indo-1 was loaded into isolated Langendorff-perfused hearts and Ca2+ transients were recorded from 15 sites over the left ventricular epicardial surface using a single core light guide. The time course of the Ca2+ transients was analysed and the duration measured and correlated with in vitro mechanical function. Results: Significant mechanical dysfunction was produced in this model of heart failure. The mean duration of the Ca2+ transients obtained from failing hearts was prolonged (156.2±3.2 ms) when compared to controls (124.9±2.6 ms, P<0.001). Delayed relaxation as measured by the maximum rate of intraventricular pressure decay was significantly correlated with the prolonged Ca2+ transients (r=−0.63, P<0.001). In addition, there was increased variation of the Ca2+ transient duration in the failing hearts. Conclusions: Coronary artery ligation-induced heart failure is associated with changes in the surviving myocardium which result in a non-uniform prolongation of Ca2+ transient duration. This suggests that there is a regional heterogeneity to the abnormal intracellular Ca2+ handling in heart failure.
Role of the JNK pathway in thrombin-induced ICAM-1 expression in endothelial cells
Authors: N MIHO, T ISHIDA, N KUWABA, M ISHIDA, K SHIMOTEABE, K TABUCHI, T OSHIMA, M YOSHIZUMI, K CHAYAMA
Journal: Cardiovascular Research (2005)

Thrombin induces leukocyte adherence to endothelial cells via increased expression of intercellular adhesion molecule-1 (ICAM-1). Although ICAM-1 expression is regulated by NF-kappaB, recent studies have suggested that additional signaling mechanisms may also be involved. The goal of this study was to determine whether mitogen-activated protein (MAP) kinases, including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 MAP kinase (p38), mediate thrombin-induced ICAM-1 expression in endothelial cells.Western blot analysis using anti-ICAM-1 antibody and luciferase assays were performed in cultured endothelial cells after addition of signal transduction inhibitors or transfection of various gene constructs. JNK kinase activity was determined by a kinase assay using c-Jun as a substrate or by Western blot analysis with anti-phospho-JNK antibody.Treatment of endothelial cells with the JNK-specific inhibitors, SP600125 or JNK inhibitory peptide 1 (JNKI1), resulted in a significant decrease in thrombin-induced ICAM-1 expression as demonstrated by Western blot analysis (67 +/- 3% and 72 +/- 7%, respectively). In contrast, inhibitors of MEK and p38 had only minimal effect. The combination of SP600125 and the NF-kappaB inhibitor, BAY11-7082, resulted in complete inhibition of thrombin-induced ICAM-1 expression. The Galpha(q) inhibitor, YM-254890, inhibited thrombin-induced JNK activation and ICAM-1 expression. Dominant-negative Ras and Rac1, but not Rho, inhibited thrombin-induced JNK activation and ICAM-1 promoter activity. Finally, thrombin-induced JNK activation and ICAM-1 promoter activity were inhibited by betaARK1ct (a Gbetagamma subunit scavenger) and Csk.These data suggest that, in concert with NF-kappaB, JNK regulates thrombin-induced ICAM-1 expression by a mechanism that is dependent on Galpha(q), Gbetagamma, Ras, Rac1 and the Src kinase family.
Interaction between the Arg16 homozygous genotype, inhaled corticosteroids and long acting beta agonists for asthma exacerbations in children? Leukotriene receptor antagonists to the rescue?
Authors: Steve Turner, Kaninika Basu, Lauren Bignell, Jon Ayres, Roger Tavendale, Brian Lipworth, Anil Mehta, Somnath Mukhopadhyay, Colin Palmer
Journal: European Respiratory Journal (2013)

Introduction. Here we test the hypothesis that when compared to children with at least one Gly16 allele, children homozygous for the Arg16 SNP of the B2AR gene are at increased risk for asthma exacerbation if treated with long acting beta agonists (LABA) and that this risk is countered by leukotriene receptor antagonist (LTRA) treatment.

Methods. Children with asthma were recruited in two cohorts using a common methodology. Details of exacerbations and asthma treatment were determined from questionnaire. DNA was extracted, Arg16Gly genotype was determined and analyses adjusted for confounders.

Results. Questionnaire and DNA were available in 2036 children, mean age 9.5 years (SD 3.8), 59% male. There were 1098 children treated with inhaled corticosteroid (ICS) monotherapy, 364 with ICS+ LABA, 164 with ICS+LTRA and 325 with ICS+LABA+LTRA. Compared to children with at least one Gly16 allele, children homozygous for Arg16 were at increased risk for exacerbations in the group with ICS monotherapy (OR 1.53 [95% CI 1.06, 2.23] p=0.025) and ICS+LABA (OR 1.96 [95% CI 1.02, 3.77] p=0.045). Arg16 homozygous genotype was not associated with increased risk for exacerbation in children treated with ICS+ LTRA± LABA. There was no evidence of an Arg16 gene dose effect.

Conclusions. There is a modest increase in asthma exacerbations among those homozygous for Arg16, compared to others, if treated with ICS±LABA. This increased risk seems to be countered by treatment with LTRA. On a whole population basis, these observations could explain many potentially avoidable exacerbations in children with asthma.
Th17 cells and tissue remodeling in atopic and contact dermatitis
Authors: D. Simon, C. Aeberhard, Y. Erdemoglu, H.‐U. Simon
Journal: Allergy (2013)

Abstract Background Eczematous skin lesions of atopic dermatitis ( AD ) as well as allergic and irritant contact dermatitis (ACD, ICD ) are characterized by the same typical clinical signs, although due to different causes. In both AD and ACD , the presence of T helper 17 cells which play an important role in host defense, has been reported. Furthermore, IL‐17 is involved in tissue repair and remodeling. This study aimed to investigate IL‐17 expression in acute eczematous skin lesions and correlate it with markers of remodeling in AD , ACD , and ICD . Methods Skin specimens were taken from positive patch test reactions to aeroallergens, contact allergens, and irritants at days 2, 3, and 4. Inflammatory cells as well as the expression of cytokines and extracellular matrix proteins were evaluated by immunofluorescence staining and confocal microscopy. Results Allergic contact dermatitis and ICD were characterized by IFN‐γ expression, whereas in AD lesions, IL‐13 expression and high numbers of eosinophils were the prominent phenotype. Expression of IL‐17, but also IL‐21 and IL‐22, was observed in all eczema subtypes. The number of IL‐22+ T cells correlated with the number of eosinophils. Markers of remodeling such as MMP‐9, procollagen‐3, and tenascin C were observed in all acute eczematous lesions, while a correlation of IL‐17+ T cell numbers with tenascin C‐expressing cells and MMP‐9+ eosinophils was apparent. Conclusion The expression of IL‐17 and related cytokines, such as IL‐22, was demonstrated in acute eczematous lesions independent of their pathogenesis. Our results suggest a potential role for IL‐17 in remodeling of the skin.
Natural history of AIDS related sclerosing cholangitis: a study of 20 cases.
Authors: A Forbes, C Blanshard, B Gazzard
Journal: Gut (1993)

A case control study of AIDS related sclerosing cholangitis indicates that it has no overall influence on prognosis, but is responsible for a striking reversal of the usual inverse correlation of age and survival in HIV infection. Pain, the principal symptom, was controlled in surviving patients with analgesics alone. Twenty consecutive patients with AIDS related sclerosing cholangitis, defined from at least two characteristic lesions at endoscopic retrograde cholangiopancreatography, were followed for a minimum of 10 months or until death. Median age was 33.5 years (range 27-50). All had abdominal pain; 11 had diarrhoea. Alkaline phosphatase was > 2X normal in 13, but the bilirubin was raised in only three. The median CD4 was 0.024 x 10(9)/l (0.005-0.341). Thirteen had cryptosporidiosis, six had active cytomegalovirus, five had no gastrointestinal pathogen. Three patients are alive without AIDS related sclerosing cholangitis symptoms at 10, 11, and 21 months. Seventeen have died at median 7 (1-23) months. Cytomegalovirus therapy had no apparent influence. The initial CD4 was < 0.11 in all those dying within six months, but correlation of CD4 with prognosis was otherwise poor. Controls, matched for age, CD4, and opportunistic infections had virtually identical overall outcome (median survival 7.5 months) and the expected worse prognosis with increasing age. Increasing age, however, appeared protective in AIDS related sclerosing cholangitis (r = +0.6; p < 0.05): this is not explained by disproportionate degrees of immunosuppression, nor by opportunistic infections.