tbuckley/cabot-search huggingface dataset:
SERPINA1 11478G-&gt;A variant, serum 1-antitrypsin, exacerbation frequency and FEV1 decline in COPD
Authors: J. K. Quint, G. C. Donaldson, M. Kumari, P. J. Talmud, J. R. Hurst
Journal: Thorax (2011)

The α(1)-antitrypsin 11478G→A polymorphism may be associated with attenuated acute α(1)-antitrypsin responses. It was hypothesised that patients with chronic obstructive pulmonary disease (COPD) and this mutation have accelerated lung function decline.To assess whether the 11478G→A polymorphism is associated with attenuated α(1)-antitrypsin responses at COPD exacerbation, and therefore accelerated lung function decline.Lung function decline by genotype was examined in the English Longitudinal Study of Ageing (ELSA; n=1805) and Whitehall II (n=2733) studies. 204 patients with COPD were genotyped in the London cohort and serum α(1)-antitrypsin concentration was measured at baseline and (n=92) exacerbation.The 11478G→A genotype frequencies did not vary between COPD cases and controls, or between COPD frequent and infrequent exacerbators. Subjects with the rare A allele experienced more rapid lung function decline in the Whitehall II (A vs non-A: 16 vs 4 ml/year p=0.02) but not ELSA (29 vs 34 ml/year, p=0.46) or London cohorts (26 vs 38 ml/year, p=0.06). Decline was not greater in frequent exacerbator A versus non-A carriers (20 vs 24 ml/year, p=0.58). Upregulation of α(1)-antitrypsin at exacerbation was not demonstrated, even in patients homozygous for the common allele (median exacerbation change -0.07 g/l 11478GG, p=0.87 and -0.09 g/l 11478AA/GA, p=0.92; p=0.90 for difference). In patients with the A allele, there was no correlation between serum α(1)-antitrypsin and serum interleukin 6 (IL-6) concentrations.The 11478G→A α(1)-antitrypsin polymorphism is not associated with increased risk of developing COPD, nor accelerated lung function decline. Serum α(1)-antitrypsin may not be upregulated early at COPD exacerbation. In patients with the 11478G→A polymorphism there was no relationship between the serum α(1)-antitrypsin and serum IL-6 concentrations.
Long-Term Outcomes of Japanese Type 2 Diabetic Patients With Biopsy-Proven Diabetic Nephropathy
Authors: Miho Shimizu, Kengo Furuichi, Tadashi Toyama, Shinji Kitajima, Akinori Hara, Kiyoki Kitagawa, Yasunori Iwata, Norihiko Sakai, Toshinari Takamura, Mitsuhiro Yoshimura, Hitoshi Yokoyama, Shuichi Kaneko, Takashi Wada
Journal: Diabetes Care (2013)

OBJECTIVE We evaluated the structural-functional relationships and the prognostic factors for renal events, cardiovascular events, and all-cause mortality in type 2 diabetic patients with biopsy-proven diabetic nephropathy. RESEARCH DESIGN AND METHODS Japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy (n = 260) were enrolled. Patients were stratified by albuminuria (proteinuria) and estimated glomerular filtration rate (eGFR) at the time of renal biopsy. The outcomes were the first occurrence of renal events (requirement of dialysis or a 50% decline in eGFR from baseline), cardiovascular events (cardiovascular death, nonfatal myocardial infarction, coronary interventions, or nonfatal stroke), and all-cause mortality. RESULTS The factors associated with albuminuria (proteinuria) regardless of eGFR were hematuria, diabetic retinopathy, low hemoglobin, and glomerular lesions. The factors associated with low eGFR regardless of albuminuria (proteinuria) were age and diffuse, nodular, tubulointerstitial, and vascular lesions. The glomerular, tubulointerstitial, and vascular lesions in patients with normoalbuminuria (normal proteinuria) and low eGFR were more advanced compared to those in patients with normoalbuminuria (normal proteinuria) and maintained eGFR. In addition, compared to patients with micro-/macroalbuminuria (mild/severe proteinuria) and low eGFR, their tubulointerstitial and vascular lesions were similar or more advanced in contrast to glomerular lesions. The mean follow-up period was 8.1 years. There were 118 renal events, 62 cardiovascular events, and 45 deaths. The pathological determinants were glomerular lesions, interstitial fibrosis and tubular atrophy (IFTA), and arteriosclerosis for renal events, arteriosclerosis for cardiovascular events, and IFTA for all-cause mortality. The major clinical determinant for renal events and all-cause mortality was macroalbuminuria (severe proteinuria). CONCLUSIONS Our study suggests that the characteristic pathological lesions as well as macroalbuminuria (severe proteinuria) were closely related to the long-term outcomes of biopsy-proven diabetic nephropathy in type 2 diabetes.
Genetic predisposition to hepatocellular carcinoma in alcoholic cirrhosis: The NCAN-PNPLA3-lipid connection?
Authors: Jean-Charles Nault, Pierre Nahon
Journal: Journal of Hepatology (2014)

Single nucleotide polymorphisms (SNPs) are nucleotide variations occurring at the DNA level in each cell of a human being. In association with environmental factors, SNPs model the phenotypic diversity in humans but are also involved in susceptibility to several illnesses including cancer [1]. The association between SNPs and hepatocellular carcinoma (HCC) has been tested in case-control and prospective cohorts on a hypothesis-driven basis in candidate gene studies. In this setting, numerous variants affecting inflammatory pathways, oxidative stress, iron metabolism or DNA repair mechanisms have been linked with HCC development in cirrhotic patients [2].
Benfotiamine Prevents Macro- and Microvascular Endothelial Dysfunction and Oxidative Stress Following a Meal Rich in Advanced Glycation End Products in Individuals With Type 2 Diabetes
Authors: Alin Stirban, Monica Negrean, Bernd Stratmann, Thomas Gawlowski, Tina Horstmann, Christian Götting, Knut Kleesiek, Michaela Mueller-Roesel, Theodor Koschinsky, Jaime Uribarri, Helen Vlassara, Diethelm Tschoepe
Journal: Diabetes Care (2006)

Diabetes is characterized by marked postprandial endothelial dysfunction induced by hyperglycemia, hypertriglyceridemia, advanced glycation end products (AGEs), and dicarbonyls (e.g., methylglyoxal [MG]). In vitro hyperglycemia-induced MG formation and endothelial dysfunction could be blocked by benfotiamine, but in vivo effects of benfotiamine on postprandial endothelial dysfunction and MG synthesis have not been investigated in humans until now.Thirteen people with type 2 diabetes were given a heat-processed test meal with a high AGE content (HAGE; 15.100 AGE kU, 580 kcal, 54 g protein, 17 g lipids, and 48 g carbohydrates) before and after a 3-day therapy with benfotiamine (1,050 mg/day). Macrovascular flow-mediated dilatation (FMD) and microvascular reactive hyperemia, along with serum markers of endothelial disfunction (E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1), oxidative stress, AGE, and MG were measured during both test meal days after an overnight fast and then at 2, 4, and 6 h postprandially.The HAGE induced a maximum reactive hyperemia decrease of -60.0% after 2 h and a maximum FMD impairment of -35.1% after 4 h, without affecting endothelium-independent vasodilatation. The effects of HAGE on both FMD and reactive hyperemia were completely prevented by benfotiamine. Serum markers of endothelial dysfunction and oxidative stress, as well as AGE, increased after HAGE. These effects were significantly reduced by benfotiamine.Our study confirms micro- and macrovascular endothelial dysfunction accompanied by increased oxidative stress following a real-life, heat-processed, AGE-rich meal in individuals with type 2 diabetes and suggests benfotiamine as a potential treatment.
Suprabasal Cells Used in Free Skin Grafts
Authors: A. L. THORNLEY, L. REINECKE
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Suprabasal Cells Used in Free Skin Grafts Get access A. L. THORNLEY, A. L. THORNLEY * Departments of Zoology and Radiotherapy University of the WitwatersrandJohannesburg, South Africa *Correspondence to: Dr. A. L. Thornley, Departments of Zoology and Radiotherapy, University of the Witwatersrand, 1 Jan Smuts Ave., Johannesburg, South Africa. Search for other works by this author on: Oxford Academic PubMed Google Scholar L. REINECKE L. REINECKE Departments of Zoology and Radiotherapy University of the WitwatersrandJohannesburg, South Africa Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 19, 4 October 1989, Pages 1512–1513, https://doi.org/10.1093/jnci/81.19.1512 Published: 04 October 1989
γδ Cells: A Right Time and a Right Place for a Conserved Third Way of Protection
Authors: Adrian C. Hayday
Journal: Annual Review of Immunology (2000)

The tripartite subdivision of lymphocytes into B cells, αβ T cells, and γδ cells has been conserved seemingly since the emergence of jawed vertebrates, more than 450 million years ago. Yet, while we understand much about B cells and αβ T cells, we lack a compelling explanation for the evolutionary conservation of γδ cells. Such an explanation may soon be forthcoming as advances in unraveling the biochemistry of γδ cell interactions are reconciled with the abnormal phenotypes of γδ-deficient mice and with the striking differences in γδ cell activities in different strains and species. In this review, the properties of γδ cells form a basis for understanding γδ cell interactions with antigens and other cells that in turn form a basis for understanding immunoprotective and regulatory functions of γδ cells in vivo. We conclude by considering which γδ cell functions may be most critical.
High-dose therapy followed by stem cell transplantation in partial response after first-line induction therapy for aggressive non-Hodgkin’s lymphoma
Authors: C. Haioun, E. Lepage, C. Gisselbrecht, B. Coiffier, Ch. Doyen, P. Morel, M. Attal, H. Tilly, E. Deconinck, Ph. Gaulard, F. Reyes
Journal: Annals of Oncology (1998)
Anti-obesity effects of α-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase
Authors: Min-Seon Kim, Joong-Yeol Park, Cherl Namkoong, Pil-Geum Jang, Je-Won Ryu, Hai-Sun Song, Ji-Young Yun, Il-Seong Namgoong, Joohun Ha, In-Sun Park, In-Kyu Lee, Benoit Viollet, Jang Hyun Youn, Hong-Kyu Lee, Ki-Up Lee
Journal: Nature Medicine (2004)
White matter integrity is associated with cognitive processing in patients treated for a posterior fossa brain tumor
Authors: S. L. Palmer, J. O. Glass, Y. Li, R. Ogg, I. Qaddoumi, G. T. Armstrong, K. Wright, C. Wetmore, A. Broniscer, A. Gajjar, W. E. Reddick
Journal: Neuro-Oncology (2012)

Children treated for posterior fossa tumors experience reduced cognitive processing speed and, after imaging, show damage to white matter (WM) tracts in the brain. This study explores relationships between white matter microstructure, assessed by fractional anisotropy (FA), and speed of cognitive processing using tract-based spatial statistics (TBSS). At 36 months after treatment with radiotherapy and chemotherapy, 40 patients completed an MRI examination and neuropsychological evaluation. Patients were matched with healthy control subjects based on age, sex, and race. Individual FA values were extracted from examinations for all voxels identified as having significant association between processing speed and FA using TBSS. The regions were labeled anatomically, and fiber tracts were grouped into larger fiber bundle categories based on their anatomical and functional associations. Analyses were performed between mean skeletal FA values in each of the fiber bundles and each of the cognitive processing scores controlling for age. Children 3 years after treatment for posterior fossa brain tumors demonstrate significantly lower processing speed associated with decreased FA, compared with their healthy peers. Commissural fibers in the corpus callosum were negatively affected by disease and therapy with detrimental consequence on patients' cognitive processing. Diffusion tensor imaging of the white matter tracts in the brain is relevant to determining potential mechanisms underlying clinically meaningful change in cognitive performance. Neuroprotective strategies are needed to preserve critical functions.
18F-FDG (fluorodeoxyglucose) uptake in focal organizing pneumonia mimicking bronchial carcinoma
Authors: Ayse Baha, Fatma Yildirim, Nurdan Kokturk, Umit Ozgur Akdemir, Sedat Demircan
Journal: European Respiratory Journal (2013)

Objective:To assess role of positron-emission tomography (PET) with fluorodeoxyglucose 18F for the diagnosis of focal organized pneumonia (OP) that may mimic bronchial carcinoma.  Patients and Methods:Medical records of 14 patients with mass-like lesions on the chest X-ray who underwent diagnostic thoracotomy with initial diagnosis of lung carcinoma were evaluated respectively.  Results:There were 10 (71.4%) male and 4 (28.6%) female patients.The mean age was 57.2±11.7 (38-85) years.Focal lung lesions were initially detected by chest radiography in 10 (71.4%) patients and by CT scan in all patients.CT scan showed single lesions in 12 (85.7%) patients.Distribution of lesions were equal for both right and left lungs.Eight (57.1%) lesions were located in upper lobes,2 (14.3%) in middle lobes and 4 (28.6%) in lower lobes.Margin of the lesions was smooth in 2 (14.2%) patients whereas it was irregular or spiculated in 8 patients (57.1%).Six (42.8%) patients had solitary nodules and eight (57.1%) patients had numerous masses;two of them with consolidation, another two with reticular pattern and one with pleural thickening.Median diameter of lesions was 3.4 (1.8 - 6.0) cm. PET was performed in all patients and hypermetabolic activity of lesions was demonstrated in all cases.Median value of maximal SUV was 3.5±2.7 (2.1-13.1).Five (35.7%) patients had intrathoracic lymphadenopathy.  Conclusion:Focal OP is a rare form of OP that is associated with discrete unifocal lesions on radiological images.It can easily be misdiagnosed as lung cancer because of mass like pattern and positive PET scans.PET scan does not give us any evidence to distinguish focal OP from lung carcinoma.
Infant feeding and allergy prevention: a review of current knowledge and recommendations. A EuroPrevall state of the art paper
Authors: K. E. C. Grimshaw, K. Allen, C. A. Edwards, K. Beyer, A. Boulay, L. B. Van Der Aa, A. Sprikkelman, S. Belohlavkova, M. Clausen, R. Dubakiene, E. Duggan, M. Reche, L. V. Marino, P. Nørhede, L. Ogorodova, A. Schoemaker, A. Stanczyk‐Przyluska, Z. Szepfalusi, E. Vassilopoulou, S. H. E. Veehof, B. J. Vlieg‐Boerstra, M. Wjst, A. E. J. Dubois
Journal: Allergy (2009)

The relationship between infant feeding patterns and the later development of food allergies has been the focus of much debate and research over the last decade. National recommendations have been made by many countries on how to feed infants to reduce the risk of food allergy but due to the lack of firm evidence the recommendations differ widely. This review has been developed as part of EuroPrevall, a European multicentre research project funded by the European Union, to document the differing feeding recommendations made across Europe, to investigate the current evidence base for any allergy prevention feeding recommendations and to identify areas where further research is needed. This review will also provide information which, when combined with the infant feeding data collected as part of EuroPrevall, will give an indication of compliance to national feeding guidelines which can be utilised to assess the effectiveness of current dissemination and implementation strategies.
The Subclass Nature and Clinical Significance of the IgG Antibody Response in Patients Undergoing Allergen‐Specific Immunotherapy
Authors: R. Djurup
Journal: Allergy (1985)

The purpose of this paper is to discuss the methodological difficulties in quantitation of human IgG subclass antibodies to allergens, to describe the subclass nature of the IgG antibody response in patients undergoing allergen‐specific immunotherapy, and to discuss the possible immunological functions and clinical significance of allergen‐specific IgG antibodies of different subclasses. Based on results obtained by use of assays with documented specificity it is concluded that the IgG antibody response during allergen‐specific immunotherapy is IgG1 and IgG4 restricted, although low levels of IgG2 and IgG3 antibodies to some allergens may occur. In most patients the early IgG antibody response is IgG1 dominated and the late IgG4 dominated. A too early or too pronounced IgG4 dominated antibody response seems to indicate a poor clinical outcome of immunotherapy with inhalant allergens, whereas a pronounced early IgG1 antibody production has been found to be associated with a decrease in synthesis of IgE antibodies to an insect venom. It is therefore proposed that an early IgG1 dominated response is necessary to induce suppression of the ongoing IgE antibody production, which in its turn may be a prerequisite for long‐lasting clinical effect. The possibility of induction of an early IgG1 dominated response in every patient by use of alternative immunotherapy procedures is discussed.
P700Serum levels of endothelin-1, matrix metalloproteinases- 2, - 9 and C- reactive protein in patients with mild and severe degree of arterial hypertension
Authors: K Kostov, A Dimitrova, A Grigoryan, S Tisheva, A Russeva, M Atanasova, K Gospodinov, A Blazhev
Journal: Cardiovascular Research (2014)

Purpose: Hemodynamic stress in arterial hypertension leading to increased production of endothelin-1 (ET-1). Changes in the extracellular matrix are controlled largely by methalloproteinase-2 (MMP-2) and methalloproteinase-9 (MMP-9) which play an important role in vascular remodeling of hypertension. C-reactive protein (CRP) is an acute phase protein which is synthesized by hepatocytes under the effect of interleukin-6 (IL-6) in inflammation. The purpose of the study was to investigate the relationship of ET-1, MMP-2, MMP-9 and CRP with the degree of arterial hypertension and the systemic and vascular inflammatory response. Methods: Three groups were formed: group I - 31 patients with mild hypertension (MH); group II - 29 patients with severe hypertension (SH); group III - 15 persons in a control group (CG). ET-1 was determined by ELISA kit of "Biomedika", MMP-2 and MMP-9 by ELISA kit of the "R&D Systems", and the CRP- through immunoturbidimetric method with monoclonal anti-CRP antibodies. The analysis used the statistical program STATGRAPHICS. Results: It was found that there was a statistically significant difference between serum concentration of ET-1 (pg/ml) at MH when compared to CG (p = 0.0189) and SH compared to CG (p = 0.0181). There is a statistically significant difference between concentration of MMP-9 (ng/ml) of SH when compared to CG (p = 0.0010) and between MH when compared to SH (p = 0.0006). There is no statistically significant difference of MMP-2 (ng/ml) between the three groups (p> 0.05). There is also a statistically significant difference between the concentrations of CRP (mg/l) at MH when compared with CG (p = 0.0170) and SH when compared with CG (p = 0.0366). Conclusions: Serum levels of ET-1 are increased in the groups with arterial hypertension, which demonstrates its role in the pathogenesis of the disease. The levels of MMP-9 are greatly reduced in patients with severe hypertension which can be used as an indicator of increased cardiovascular risk in these patients. Serum levels of MMP-2 do not show specific changes at the different degrees of hypertension. Based on our experimental data can be concluded that the levels of MMP-9 in arterial hypertension are defined by complex causes - the degree of hypertension, drug therapy and accompanying cardiovascular diseases and complications. The average levels of CRP at MH and SH are significantly increased which confirms the pathogenetic relationship of arterial hypertension with systemic and vascular inflammation.
Transcriptional activation of the Lats1 tumor suppressor gene in tumors of CUX1 transgenic mice
Authors: Rania Siam, Ryoko Harada, Chantal Cadieux, Robert Battat, Charles Vadnais, Alain Nepveu
Journal: Molecular Cancer (2009)

Abstract Background Lats1 (large tumor suppressor 1) codes for a serine/threonine kinase that plays a role in the progression through mitosis. Genetic studies demonstrated that the loss of LATS1 in mouse, and of its ortholog wts (warts) in Drosophila, is associated with increased cancer incidence. There are conflicting reports, however, as to whether overexpression of Lats1 inhibits cell proliferation. CUX1 is a transcription factor that exists in different isoforms as a result of proteolytic processing or alternative transcription initiation. Expression of p110 and p75 CUX1 in transgenic mice increases the susceptibility to cancer in various organs and tissues. In tissue culture, p110 CUX1 was shown to accelerate entry into S phase and stimulate cell proliferation. Results Genome-wide location arrays in cell lines of various cell types revealed that Lats1 was a transcriptional target of CUX1. Scanning ChIP analysis confirmed that CUX1 binds to the immediate promoter of Lats1 . Expression of Lats1 was reduced in cux1 -/- MEFs, whereas it was increased in cells stably or transiently expressing p110 or p75 CUX1. Reporter assays confirmed that the immediate promoter of Lats1 was sufficient to confer transcriptional activation by CUX1. Lats1 was found to be overexpressed in tumors from the mammary gland, uterus and spleen that arise in p110 or p75 CUX1 transgenic mice. In tissue culture, such elevated LATS1 expression did not hinder cell cycle progression in cells overexpressing p110 CUX1. Conclusion While inactivation of Lats1 / wts in mouse and Drosophila can increase cancer incidence, results from the present study demonstrate that Lats1 is a transcriptional target of CUX1 that can be overexpressed in tumors of various tissue-types. Interestingly, two other studies documented the overexpression of LATS1 in human cervical cancers and basal-like breast cancers. We conclude that, similarly to other genes involved in mitotic checkpoint, cancer can be associated with either loss-of-function or overexpression of Lats1 .
Impairment of `ileostomy adaptation' in patients after ileal resection
Authors: G. L. Hill, W. S. J. Mair, J. C. Goligher
Journal: Gut (1974)

Ileostomists claim that in the months following the establishment of an ileostomy, the faecal output decreases in volume and becomes less fluid. It is claimed that this `ileostomy adaptation9 does not occur in those patients who have had an ileal resection. To determine whether ileostomy adaptation does occur and to examine its physiological mechanisms, 10 ileostomy patients were studied. Five had had ileal resection and five had not. The output of fluid, sodium, and potassium from the ileostomy was studied in each patient for the first 11 days after ileostomy and again at six months. Those patients in whom the terminal ileum was preserved had small faecal outputs of fluid and sodium from the outset, and the water content of the effluent was significantly less at six months. After rapid expansion of the extracellular fluid by intravenous saline, there was a marked increase in faecal volume and sodium output. In those patients with an ileal resection, the faecal volume and sodium output were more than two and a half times greater than those for the non-resected group. At six months there was no change in either the volume or chemistry of the effluent. After intravenous saline, no faecal response was observed. It is therefore concluded that ileostomy adaptation does occur and it is a response of the intestine to conserve body salt. This response is lacking in ileostomists who have had an ileal resection.