tbuckley/cabot-search huggingface dataset:
Genetic contribution of <i>DKK-1</i> polymorphisms to RA structural severity and DKK-1 level of expression
Authors: Corinne Miceli-Richard, Kimberly E Taylor, Joanne Nititham, Raphaèle Seror, Gaetane Nocturne, Saida Boudaoud, Philippe Dieude, Arnaud Constantin, Valérie Devauchelle-Pensec, Gabriel J Tobón, Xavier Mariette, Lindsey A Criswell
Journal: Annals of the Rheumatic Diseases (2015)

There is growing interest in the role of Dickkopf-1 (DKK-1), an inhibitor of the Wnt signalling pathway, in subchondral bone erosions in rheumatoid arthritis (RA). de Rooy et al 1 have previously reported that polymorphisms within the DKK-1 locus might contribute to RA structural severity. In fact, rs1896368 was significantly associated with an increased rate of joint destruction with a 1.02-fold (95% CI 1.01 to 1.04) progression rate per year per minor allele (additive model). Patients carrying the rs1896368 at-risk allele also had significantly higher serum levels of DKK-1. Several other polymorphisms located within the DKK-1 locus were associated with a faster structural progression.1 We aimed to replicate these findings in the ESPOIR cohort which is a prospective, multicentre French cohort of patients with early arthritis.2 We took advantage of the large number of patients assessed within the ESPOIR cohort, with iterative and centralised radiological evaluation, which allowed for studying the role of DKK-1 polymorphisms as predictive markers of structural damage and/or as genetic modulators of DKK-1 expression.3 Patients had to be free of disease-modifying antirheumatic drugs and biologics to be included in the cohort, thus avoiding a bias due …
Metastasis Inhibition of Different Tumor Types by Purified Laminin Fragments and a Heparin-Binding Fragment of Fibronectin
Authors: J. B. McCarthy, A. P. N. Skubitz, S. L. Palm, L. T. Furcht
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Metastasis Inhibition of Different Tumor Types by Purified Laminin Fragments and a Heparin-Binding Fragment of Fibronectin Get access James B. McCarthy, James B. McCarthy Search for other works by this author on: Oxford Academic PubMed Google Scholar Amy P. N. Skubitz, Amy P. N. Skubitz Search for other works by this author on: Oxford Academic PubMed Google Scholar Sally L. Palm, Sally L. Palm Search for other works by this author on: Oxford Academic PubMed Google Scholar Leo T. Furcht Leo T. Furcht 3University of MinnesotaBox 609, Mayo Memorial Building, Department of Laboratory Medicine and Pathology, Minneapolis, MN 55455 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 2, 16 March 1988, Pages 108–116, https://doi.org/10.1093/jnci/80.2.108 Published: 16 March 1988 Article history Received: 26 May 1987 Accepted: 14 September 1987 Published: 16 March 1988
Chest expansion in school-age children with mild bronchial asthma
Authors: Katerina Neumannova, Jakub Zatloukal, Jana Rydlova, Dana Dvorakova
Journal: European Respiratory Journal (2012)

Introduction 

The presence of persistent bronchial asthma (BA) is usually connected with limited chest expansion (CE) [1], but there are no reference values to express if there is a serious limitation.

Aims 

To evaluate an effect of a 4-week pulmonary rehabilitation programme (PRP) on CE in school-age children with mild BA.

Methods 

One-hundred-and-fourteen children with BA (aged 12.0±2.6 years) were examined and recruited for the intervention group (I), which attended a 4-week PRP including respiratory physiotherapy, inhalation, physical activity training in group sessions. Two-hundred-and-eight healthy children (aged 11.9±2.0 years) were examined and assigned to the control group (C). Both groups underwent a CE assessment, which was performed with a tape cloth measure at the level of 4th intercostal space (IC) and at the level of xiphoid process (XP).

Results 

CE of the I group was significantly lower at baseline compared to the C group. After the 4-week PRP a significant improvement was achieved that resulted in a presence of not significant difference between the I and C group in almost all subgroups.

View this table:

CE of BA and healthy children





Conclusion 

The PRP led to a significant improvement of chest expansion in BA children, who had CE previously decreased.

Reference: 

1. Lopes, E. A. et al. Assessment of muscle shortening and static posture in children with persistent asthma. Eur J Pediatr 2007; 166: 715-721.

Study was supported by grants of the Palacky University – FTK\_2011\_010; FTK_2012:023.
Respiratory adjustment to chronic metabolic alkalosis in man
Authors: Roberta M. Goldring, Paul J. Cannon, Henry O. Heinemann, Alfred P. Fishman
Journal: Journal of Clinical Investigation (1968)

This study examined the ventilatory adjustment to chronic metabolic alkalosis induced under controlled conditions in normal human volunteers. Metabolic alkalosis induced by buffers (sodium bicarbonate, trishydroxymethylamine methane) or ethacrynic acid was associated with alveolar hypoventilation, as evidenced by a rise in arterial Pco(2), a fall in arterial Po(2), a reduced resting tidal volume, and a diminished ventilatory response to CO(2) inhalation. Alveolar hypoventilation did not occur when metabolic alkalosis was induced in the same subjects by thiazide diuretics or aldosterone despite comparable elevations of the arterial blood pH and bicarbonate concentration.The different ventilatory responses of the two groups could not be ascribed to differences among individuals comprising each group, pharmacological effects of the alkalinizing agents, differences in the composition of the lumber spinal fluid, changes in extracellular fluid volume, or sodium and chloride balance.The differences in ventilatory adjustments were associated with differences in the patterns of hydrogen and potassium ion balance during the induction of alkalosis. Alveolar hypoventilation occurred when hydrogen ions were buffered (sodium bicarbonate, trishydroxymethylamine methane) or when renal hydrogen ion excretion was increased (ethacrynic acid). Alveolar hypoventilation did not occur when induction of similar degrees of extracellular alkalosis was accompanied by marked potassium loss and no demonstrable increase in external hydrogen loss (thiazides and aldosterone).These observations suggest that respiratory depression does not necessarily accompany extracellular alkalosis but depends on the effect of the mode of induction of the alkalosis on the tissues involved in the control of ventilation.
Metalloproteinase-2, -7 and -9 and tissue inhibitor of metalloproteinase-1 and -2 expression in normal, hyperplastic and neoplastic endometrium: a clinical-pathological correlation study
Authors: O. Graesslin, A. Cortez, R. Fauvet, M. Lorenzato, P. Birembaut, E. Daraï
Journal: Annals of Oncology (2006)
The Effect of Angiotensin II on the Blood Pressure in Humans with Hypertensive Disease*
Authors: Norman M. Kaplan, Jack G. Silah
Journal: Journal of Clinical Investigation (1964)

A reduced sensitivity to the pressor effect of exogenous angiotensin 1 has been observed in dogs with increased levels of endogenous angiotensinlike activity (1). Patients with secondary hyperaldosteronism, where levels of endogenous angiotensin are thought to be elevated, also have a reduced pressor responsiveness to exogenous angiotensin, but not to l-norepinephrine (2, 3). A reduced pressor responsiveness to angiotensin might then be expected with renovascular hypertension, which is said to be associated with increased levels of circulating renin and angiotensin (4). The pressor responses to exogenous angiotensin and, in some patients, to l-norepinephrine were initially examined in a variety of experimental and pathological situations where the levels of endogenous angiotensin have either been shown or are believed to be altered. Patients with various hypertensive diseases were then studied. The results suggest that the pressor responsiveness to angiotensin may be a useful clinical test for the diagnosis of renovascular hypertension.
Functional impairment of renal afferent arteriolar voltage-gated calcium channels in rats with diabetes mellitus.
Authors: P K Carmines, K Ohishi, H Ikenaga
Journal: Journal of Clinical Investigation (1996)

Experiments were performed to test the hypothesis that diabetes mellitus is associated with impaired afferent arteriolar responsiveness to opening of voltage-gated calcium channels. Diabetes was induced by injection of streptozocin (65 mg/kg, i.v.) and insulin was administered via an osmotic minipump to achieve moderate hyperglycemia. Sham rats received vehicle treatments. 2 wk later, the in vitro blood-perfused juxtamedullary nephron technique was used to allow videomicroscopic measurement of afferent arteriolar contractile responses to increasing bath concentrations of either Bay K 8644 or K+. Baseline afferent arteriolar diameter in kidneys from diabetic rats (26.4+/-1.2 microm) exceeded that of Sham rats (19.7+/-1.0 microm). Bay K 8644 evoked concentration-dependent reductions in afferent diameter in both groups of kidneys; however, arterioles from Sham rats responded to 1 nM Bay K 8644 while 100 nM Bay K 8644 was required to contract arterioles from diabetic rats. The EC50 for K+-induced reductions in afferent arteriolar diameter was greater in diabetic kidneys (40+/-4 mM) than in kidneys from Sham rats (28+/-4 mM; P < 0.05). In afferent arterioles isolated by microdissection from Sham rats and loaded with fura 2, increasing bath [K+] from 5 to 40 mM evoked a 98+/-12 nM increase in intracellular Ca2+ concentration ([Ca2+]i). [Ca2+]i responses to 40 mM K+ were suppressed in afferent arterioles from diabetic rats (delta = 63+/-5 nM), but were normalized by decreasing bath glucose concentration from 20 to 5 mM. These observations indicate that the early stage of insulin-dependent diabetes mellitus is associated with a functional defect in afferent arteriolar L-type calcium channels, an effect which may contribute to suppressed afferent arteriolar vasoconstrictor responsiveness and promote glomerular hyperfiltration.
Comparative electron microscopic study between Mendes da Costa's disease and recessive epidermolysis bullosa dystrophica
Authors: M. L. GEERTS, J. OVERBEKE, A. KINT, R. H. CORMANE
Journal: British Journal of Dermatology (1978)

An electron microscopic study of Mendes da Costa's disease (MCD) has been undertaken to determine whether this disease is a variant of epidermolysis bullosa dystrophica, or should be classified as a separate disease entity. It was shown that in MCD lacunae occur in the lower layers of the epidermis, in the presence of normal anchoring fibrils. In the recessive form of epidermolysis bullosa dystrophica (EBD), however, no lacunae were found in the epidermis, and anchoring fibrils were absent. These findings support the concept that MCD should not be considered as a special form of epidermolysis bullosa dystrophica.
A new dawn for the use of traditional Chinese medicine in cancer therapy
Authors: Harendra S Parekh, Gang Liu, Ming Q Wei
Journal: Molecular Cancer (2009)

Although traditional Chinese medicine has benefitted one fifth of the world's population in treating a plethora of diseases, its acceptance as a real therapeutic option by the West is only now emerging. In light of a new wave of recognition being given to traditional Chinese medicine by health professionals and regulatory bodies in the West, an understanding of their molecular basis and highlighting potential future applications of a proven group of traditional Chinese medicine in the treatment of a variety of cancers is crucial – this is where their calling holds much hope and promise in both animal and human trials. Furthermore, the rationale for combining conventional agents and modern biotechnological approaches to the delivery of traditional Chinese medicine is an avenue set to revolutionize the future practice of cancer medicine – and this may well bring on a new dawn of therapeutic strategies where East truly meets West.
Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial)
Authors: S M M Verstappen, J W G Jacobs, M J van der Veen, A H M Heurkens, Y Schenk, E J ter Borg, A A M Blaauw, J W J Bijlsma
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Background:</h3> To investigate whether intensive treatment with methotrexate (MTX) according to a strict protocol and a computerised decision program is more beneficial compared to conventional treatment with MTX in early rheumatoid arthritis. <h3>Methods:</h3> In a two-year multicentre open label strategy trial, 299 patients with early rheumatoid arthritis were randomly assigned to the intensive strategy group or the conventional strategy group. Patients in both groups received MTX, the aim of treatment being remission. Patients in the intensive treatment group came to the outpatient clinic once every month; adjustment of the MTX dosage was tailored to the individual patient on the basis of predefined response criteria, using a computerised decision program. Patients of the conventional strategy group came to the outpatient clinic once every three months; they were treated according to common practice. Cyclosporine was added if patients had an inadequate response to maximal tolerated MTX doses. <h3>Results:</h3> Seventy six (50%) patients in the intensive strategy group achieved at least one period of remission during the two year trial, versus 55 patients (37%) in the conventional strategy group (p = 0.03). Areas under the curve for nearly all clinical variables were significantly lower—that is, there was a better clinical effect for the intensive treatment group compared with the conventional treatment group. <h3>Conclusion:</h3> The results of this study show that it is possible to substantially enhance the clinical efficacy early in the course of the disease by intensifying treatment with MTX, aiming for remission, tailored to the individual patient. Furthermore, participating rheumatologists indicated that the computerised decision program could be a helpful tool in their daily clinical practice.
Rapid Detection of Myocardial Infarction by Subsecond, Free-Breathing Delayed Contrast-Enhancement Cardiovascular Magnetic Resonance
Authors: Burkhard Sievers, Michael D. Elliott, Lynne M. Hurwitz, Timothy S.E. Albert, Igor Klem, Wolfgang G. Rehwald, Michele A. Parker, Robert M. Judd, Raymond J. Kim
Journal: Circulation (2007)

An ultrafast, delayed contrast-enhancement cardiovascular magnetic resonance technique that can acquire subsecond, "snapshot" images during free breathing (subsecond) is becoming widely available. This technique provides myocardial infarction (MI) imaging with complete left ventricular coverage in < 30 seconds. However, the accuracy of this technique is unknown.We prospectively compared subsecond imaging with routine breath-hold delayed contrast-enhancement cardiovascular magnetic resonance (standard) in consecutive patients. Two cohorts with unambiguous standards of truth were prespecified: (1) patients with documented prior MI (n=135) and (2) patients without MI and with low likelihood of coronary disease (lowest Framingham risk category; n=103). Scans were scored masked to identity and clinical information. Sensitivity, specificity, and accuracy of subsecond imaging for MI diagnosis were 87%, 96%, and 91%, respectively. Compared with the standard technique (98%, 100%, 99%), the subsecond technique had modestly reduced sensitivity (P=0.0001), but specificity was excellent. Missed infarcts were generally small or subendocardial (87%). Overall, regional transmural extent of infarction scores were highly concordant (2083/2294; 91%); however, 51 of 337 regions (15%) considered predominantly infarcted (> 50% transmural extent of infarction) by the standard technique were considered viable (< or = 25% transmural extent of infarction) by the subsecond technique. Quantitative analysis demonstrated moderately reduced contrast-to-noise ratios for subsecond imaging between infarct and remote myocardium (12.0+/-7.2 versus 20.1+/-6.6; P<0.0001) and infarct and left ventricular cavity (-2.5+/-2.7 versus 3.6+/-3.7; P<0.0001).MI can be rapidly detected by subsecond delayed contrast-enhancement cardiovascular magnetic resonance during free breathing with high accuracy. This technique could be considered the preferred approach in patients who are more acutely ill or unable to hold their breath. However, compared with standard imaging, sensitivity is mildly reduced, and the transmural extent of infarction may be underestimated.
Normal immunoglobulin G (IgG) for therapeutic use (intravenous Ig) contain antiidiotypic specificities against an immunodominant, disease-associated, cross-reactive idiotype of human anti-thyroglobulin autoantibodies.
Authors: G Dietrich, M D Kazatchkine
Journal: Journal of Clinical Investigation (1990)

Pooled normal polyspecific IgG for therapeutic use (IVIg) contain anti-idiotypes against idiotypic determinants expressed by autoantibodies from patients with a variety of autoimmune diseases. In the present study, antiidiotypes in IVIg are shown to recognize a cross-reactive idiotype on human anti-thyroglobulin (TG) autoantibodies, that was defined by heterologous antiidiotypic antibodies, termed anti-T44 antibodies. The T44 idiotype is located outside the antibody-combining site of anti-TG autoantibodies. F(ab')2 fragments from anti-T44 antibodies inhibited the binding of IVIg to affinity-purified F(ab')2 anti-TG autoantibodies. Anti-T44 antibodies bound to F(ab')2 fragments of patients' antibodies, which were retained on an affinity column of Sepharose-bound F(ab')2 fragments from IVIg, but not to F(ab')2 fragments from the effluent of the column. The T44 idiotype was expressed on antibodies that bound to IVIg from eight of nine patients with autoimmune thyroiditis, but not on IVIg-binding Igs from healthy individuals. A small amount of the T44 idiotype was also expressed on the fraction of IVIg that bound to itself upon affinity chromatography. The T44 idiotype was cross-reactive between antibodies from patients with autoimmune thyroiditis. Thus, IVIg contain antiidiotypic antibodies directed against an immunodominant disease-associated cross-reactive alpha-idiotype of human anti-TG autoantibodies. These results support the concept that IVIg may be beneficial in selected autoimmune diseases by modulating the function of the idiotypic network.
Endobronchial ultrasound guided biopsy followed by real-time PCR is an applicable method to analyse SHOX2 methylation level in mediastinal lymph nodes of lung cancer patients
Authors: Katrin Bähner, Lutz Freitag, Claudia Ivascu, Dirk Theegarten, Jeremias Wohlschläger, Roze Imsak, Kaid Darwiche
Journal: European Respiratory Journal (2012)

Previous studies have shown that SHOX2 DNA methylation can potentially serve as a tumour marker in lung cancer patients. DNA methylation of SHOX2 could have been assessed in serum and bronchial aspirates.

This study aimed to find out, if there is an opportunity to analyse SHOX2 DNA methylation level in lymph node tissue obtained by endobronchial ultrasound guided biopsy in context of diagnosis and lymph node staging.

Tissue from mediastinal lymph nodes was taken from ten patients with proven lung cancer. In five cases the tissue was obtained by transbronchial forceps biopsy, in the other five by transbronchial needle aspiration (TBNA). Samples were treated with bisulphite, excluding the unmethylated SHOX2 DNA from amplification. A real-time PCR duplex assay was then used to quantify the amount of total DNA on one hand and the number of methylated SHOX2 gene copies on the other hand. Finally the DNA methylation level of SHOX2was determined relating the number of methylated SHOX2 gene copies to the total amount of DNA.

DNA was successfully extracted and analysed by real-time PCR duplex assay in all samples. Valid measurements of SHOX2 DNA methylation level could be achieved in all samples, as well.

Endobronchial ultrasound guided biopsy as a minimal invasive method followed by real-time PCR is an applicable procedure to analyse SHOX2 DNA methylation level in mediastinal lymph nodes of lung cancer patients.

These outcomes allow comparing SHOX2 DNA methylation level in patients suspected to have lung cancer in further studies. DNA methylation level of SHOX2 has the potential to be a useful biomarker in lung cancer.
Increased Efficacy of Breast Cancer Chemotherapy in Thrombocytopenic Mice
Authors: Mélanie Demers, Benoit Ho-Tin-Noé, Daphne Schatzberg, Janie J. Yang, Denisa D. Wagner
Journal: Cancer Research (2011)

Platelets contribute to homeostasis of the tumor vasculature by helping prevent hemorrhage. Thus, we hypothesized that inducing thrombocytopenia would increase tumor vascular leakiness and facilitate the effective delivery of chemotherapeutic agents to tumors. In a mammary carcinoma murine model, platelet depletion induced bleeding specifically at the tumor site, favoring the accumulation of fluorescently labeled microspheres only in the tumor. Moreover, induction of thrombocytopenia in tumor-bearing mice before injection of paclitaxel increased its intratumoral accumulation and reduced growth of both slow- and fast-growing tumors, compared with mice with normal platelet counts that were treated only with paclitaxel. Histologic analysis confirmed the expectation of an increase in tumor apoptosis and a reduction in tumor proliferation in thrombocytopenic mice receiving chemotherapy. No increased toxicity was seen in other organs or blood cells. Taken together, our results indicate that low platelet count selectively induces leakiness of tumor vessels and favors the delivery of chemotherapy to tumor sites, enhancing its tumoricidal effects.
Serum 2′,5′-oligoadenylate synthetase activity during interferon treatment of chronic hepatitis B
Authors: Michiko Shindo, Tadao Okuno, Masayuki Matsumoto, Makoto Takeda, Tatsuro Takino, Junko Sokawa, Akira Iwata, Yoshihiro Sokawa
Journal: Hepatology (1988)

We measured 2′,5′-oligoadenylate synthetase activities in serum and peripheral blood mononuclear cells from 10 patients with chronic hepatitis B who were being treated with interferon so as to determine whether 2′,5′-oligoadenylate synthetase activity in serum reflected 2′,5′-oligoadenylate synthetase activity in peripheral blood mononuclear cells, and whether it could be used to monitor interferon treatment. Pretreatment values of 2′,5′-oligoadenylate synthetase activity in patients' serum and peripheral blood mononuclear cells were not statistically different from values from control subjects. When interferon was administered, serum levels of 2′,5′-oligoadenylate synthetase began to rise within 3 hr, reached peak values at 12 hr and then declined. The levels of 2′,5′-oligoadenylate synthetase activity both in serum and peripheral blood mononuclear cells increased substantially during interferon treatment, ranging 2- to 50-fold greater than initial levels. The levels of 2′,5′-oligoadenylate synthetase in serum correlated closely with levels in peripheral blood mononuclear cells. In addition, when the levels of 2′,5′-oligoadenylate synthetase rose during interferon administration, serum hepatitis B virus DNA polymerase values fell, and, in some cases, DNA polymerase rose again when 2′,5′-oligoadenylate synthetase fell after discontinuation of interferon. These findings' suggest that 2′,5′-oligoadenylate synthetase activity in serum accurately reflects the antiviral effect of interferon and could be used to monitor interferon treatment.