tbuckley/cabot-search huggingface dataset:
NAFLD and extrahepatic cancers: have a look at the colon
Authors: H. Tilg, A. M. Diehl
Journal: Gut (2011)

A high body-mass index has been demonstrated to be associated with an increased mortality not only from cardiovascular disease but also from certain cancers.1 An impressive body of evidence further indicates that the risk of colorectal adenoma and cancer is increased in subjects with obesity and related metabolic syndrome.2 Obesity has indeed a direct and independent relationship with colorectal cancer, although the strength of the association with general obesity seems to be smaller than previously reported.3 A recent French study suggests that obesity and weight gain are associated with early colorectal carcinogenesis in women especially regarding the distal colon.4 Several other studies identified an increased risk of developing also other gastrointestinal cancers such as oesophageal adenocarcinoma in the obese population. The association between obesity and other gastrointestinal malignancies, however, has been less robust. Non-alcoholic fatty liver disease (NAFLD) has arisen as one of the most prevalent liver diseases worldwide and usually develops in obese subjects. Pathophysiological insights into this disorder have improved substantially in recent years and, in addition, various clinical associations, such as insulin resistance, diabetes and cardiovascular diseases, have been well recognised. …
Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial
Authors: Matthias Thielmann, Eva Kottenberg, Petra Kleinbongard, Daniel Wendt, Nilgün Gedik, Susanne Pasa, Vivien Price, Konstantinos Tsagakis, Markus Neuhäuser, Jürgen Peters, Heinz Jakob, Gerd Heusch
Journal: The Lancet (2013)
Expression of RPE65, a putative receptor for plasma retinol-binding protein, in nonmelanocytic skin tumours
Authors: G. Hinterhuber, K. Cauza, R. Dingelmaier-Hovorka, E. Diem, R. Horvat, K. Wolff, D. Foedinger
Journal: British Journal of Dermatology (2005)

In a recent report we described RPE65, a protein originally characterized in retinal pigment epithelium, to be expressed in normal human epidermis. RPE65 is suspected to be involved in cellular uptake of retinol which is transported in the bloodstream complexed with plasma retinol-binding protein.To evaluate protein and mRNA expression of RPE65 in actinic keratosis (AK), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) compared with normal skin.RPE65 mRNA expression in skin tumours relative to normal skin of the respective donor was studied by real-time polymerase chain reaction in AK (n = 15), invasive SCC (n = 30) and BCC (n = 18). A peptide-specific anti-RPE65 antibody was used for immunohistochemical staining of formalin-fixed and paraffin-embedded tissue sections of the respective tumours.RPE65 mRNA expression was reduced in AK. A highly significant reduction of RPE65 mRNA was observed in invasive SCC relative to normal skin of the respective donors. Immunohistochemistry revealed a continuous staining of basal and suprabasal keratinocytes in normal human epidermis. RPE65 in AK shown by immunohistochemical staining was reduced and quite irregular, whereas invasive SCC revealed no staining of tumour cells with the anti-RPE65 antibody. RPE65 mRNA values were elevated, whereas immunohistochemical staining for RPE65 protein was heterogeneous in BCC.These results suggest progressive downregulation of RPE65 from AK to invasive SCC.
Atopy, airway responsiveness, and genes.
Authors: M Boguniewicz, A Hayward
Journal: Thorax (1996)

Asthma is a manifestation of bronchial hyperreactivity (BHR) and forms part of the spectrum of atopic disease.Some pedigree studies of atopy have suggested linkage with the high-affinity IgE receptor (FcE RI1) gene on chromosome 11q13, but others find no linkage.The molecular genetics of asthma and BHR have not been studied in the general population.We examined the genetic linkage of the Fce RIf gene with clinical asthma and the underlying phenotypes of BHR (to methacholine) and atopy (defined by skinprick testing) in 123 affected sibling-pairs recruited from the general population.We found evidence of significant linkage of a highly polymorphic microsatellite marker in the fifth intron of the FcE RI/, gene to a diagnosis of asthma (18.0%excess of shared alleles, P=0.002) and to BHR (21.7% excess of shared alleles, P= 0.00 1).Significant linkage was also observed in siblings sharing BHR when those with atopy were excluded (32.8% excess of shared alleles, P = 0.004).Atopy in the absence of BHR did not show significant linkage to the FcE RI, gene (7.2% excess of shared alleles, P= 0 124).These findings suggest that mutations in the FcE RIft gene or a closely linked gene influence the BHR underlying asthma, even in the absence of atopy.(
Television Viewing Time and Mortality
Authors: D.W. Dunstan, E.L.M. Barr, G.N. Healy, J. Salmon, J.E. Shaw, B. Balkau, D.J. Magliano, A.J. Cameron, P.Z. Zimmet, N. Owen
Journal: Circulation (2010)

Background— Television viewing time, the predominant leisure-time sedentary behavior, is associated with biomarkers of cardiometabolic risk, but its relationship with mortality has not been studied. We examined the associations of prolonged television viewing time with all-cause, cardiovascular disease (CVD), cancer, and non-CVD/noncancer mortality in Australian adults. Methods and Results— Television viewing time in relation to subsequent all-cause, CVD, and cancer mortality (median follow-up, 6.6 years) was examined among 8800 adults ≥25 years of age in the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). During 58 087 person-years of follow-up, there were 284 deaths (87 CVD deaths, 125 cancer deaths). After adjustment for age, sex, waist circumference, and exercise, the hazard ratios for each 1-hour increment in television viewing time per day were 1.11 (95% confidence interval [CI], 1.03 to 1.20) for all-cause mortality, 1.18 (95% CI, 1.03 to 1.35) for CVD mortality, and 1.09 (95% CI, 0.96 to 1.23) for cancer mortality. Compared with a television viewing time of &lt;2 h/d, the fully adjusted hazard ratios for all-cause mortality were 1.13 (95% CI, 0.87 to 1.36) for ≥2 to &lt;4 h/d and 1.46 (95% CI, 1.04 to 2.05) for ≥4 h/d. For CVD mortality, corresponding hazard ratios were 1.19 (95% CI, 0.72 to 1.99) and 1.80 (95% CI, 1.00 to 3.25). The associations with both cancer mortality and non-CVD/noncancer mortality were not significant. Conclusions— Television viewing time was associated with increased risk of all-cause and CVD mortality. In addition to the promotion of exercise, chronic disease prevention strategies could focus on reducing sitting time, particularly prolonged television viewing.
Effect of angiotensin-converting enzyme inhibition in HIV-associated nephropathy.
Authors: G C Burns, S K Paul, I R Toth, S L Sivak
Journal: Journal of the American Society of Nephrology (1997)

Angiotensin-converting enzyme inhibition (ACEI) delays progression of diabetic and nondiabetic renal disease. This study examined the effect of fosinopril, 10 mg by mouth daily, in HIV-associated nephropathy (HIV-AN). Twenty patients with HIV-AN were studied. Of 11 patients with non-nephrotic-range proteinuria, 7 received treatment and 4 did not. Average baseline creatinine (mg/dl) for treated and nontreated patients was 1.3 +/- 0.24 and 1.0 +/- 0.25, respectively (P = 0.07). At 24 wk, creatinine of treated and nontreated patients was 1.5 +/- 0.34 and 4.9 +/- 2.4 (P = 0.006). Average baseline 24-h urine protein excretion (g/d) for treated and nontreated patients was 1.6 +/- 0.68 and 0.78 +/- 0.39, respectively (P = 0.02). At 24 wk, 24-h protein excretion of treated and non-treated patients was 1.25 +/- 0.86 and 8.5 +/- 1.4 (P = 0.006). Of nine patients with nephrotic-range proteinuria, five were treated and four were not. Average baseline creatinine for treated and nontreated patients was 1.7 +/- 0.46 and 1.9 +/- 0.42, respectively (P = 0.4). At 12 wk, creatinine for treated and nontreated patients was 2.0 +/- 1.0 and 9.2 +/- 2.0 (P = 0.02). The baseline 24-h protein excretion for treated and nontreated patients was 5.4 +/- 1.6 and 5.2 +/- 0.97 (P = 0.9). At 12 wk, 24-h protein excretion for treated and nontreated was 2.8 +/- 1.0 and 10.5 +/- 3.5 (P = 0.008). These preliminary data suggest that treatment with ACEI may stabilize serum creatinine and 24-h protein excretion for up to 24 wk in patients with non-nephrotic-range proteinuria and for up to 12 wk in patients with nephrotic-range proteinuria when initial serum creatinine is < or = 2.0 mg/dl. Furthermore, the renin-angiotensin system may play a role in HIV-AN, and early treatment with ACEI may be beneficial in HIV-AN.
Prognosis in T2N0M0 stage I breast carcinoma: a 20-year follow-up study.
Authors: P P Rosen, S Groshen, D W Kinne
Journal: Journal of Clinical Oncology (1991)

In a study of prognosis in node-negative breast carcinoma, we investigated 293 T2N0M0 patients treated by mastectomy and axillary dissection with a median follow-up of 19.8 years. The probability of surviving 20 years considering all causes of death was 41.3% +/- 3.0%. Recurrence-free survival (Kaplan-Meier estimate) was 68.6% +/- 3% at 10 years and 63.2% +/- 3.1% at 20 years. The estimated probability of cure determined by the method of Brinkley and Haybittle was 63% (95% confidence interval [Cl], 55% to 72%). Prognosis was related to primary tumor size with the best separation (P = .06) when tumors from 2.1 to 3.0 cm (33% chance of recurrence at 20 years) and from 3.1 to 5.0 cm (44% chance of recurrence at 20 years) were compared. The histologic tumor type was prognostically important. Recurrence at 20 years was not significantly different for patients with invasive duct (34%) and lobular (42%) carcinoma. Women with special types (medullary, mucinous, papillary, etc) of carcinoma had a 25% chance of recurrence. Subsequent contralateral breast carcinoma was diagnosed in 29 patients, and four of these were fatal, accounting for only 4.6% of breast carcinoma deaths. Thirty-two patients (10.9%) developed a nonmammary malignant neoplasm (NMMN) after the ipsilateral breast carcinoma, and 69% of these lesions were fatal. Although the chances of recurrence at 20 years related to tumor size and type did not differ statistically in the series, there were trends that suggest that T2N0M0 patients can be stratified into recurrence risk groups based on tumor size and histologic type. These factors should be taken into consideration in the design and analysis of clinical adjuvant therapy trials. Measures for the early detection of common NMMNs should be included in the routine follow-up of T2N0M0 breast carcinoma patients.
Does real-time perfusion have any incremental value for the sensitivity and specificity of dobutamine stress echocardiography?
Authors: Melda S. Dolan, Amr El-Shafei, Michelle Bierig, Amit Doshi, Jiri Sklenar, Toniya Singh, Denice Sheriff, Alan Maniet, Mort Kem, Arthur J. Labovitz
Journal: Journal of the American College of Cardiology (2002)
Overexpression of Mafb in Podocytes Protects against Diabetic Nephropathy
Authors: Naoki Morito, Keigyou Yoh, Masami Ojima, Midori Okamura, Megumi Nakamura, Michito Hamada, Homare Shimohata, Takashi Moriguchi, Kunihiro Yamagata, Satoru Takahashi
Journal: Journal of the American Society of Nephrology (2014)

We previously showed that the transcription factor Mafb is essential for podocyte differentiation and foot process formation. Podocytes are susceptible to injury in diabetes, and this injury leads to progression of diabetic nephropathy. In this study, we generated transgenic mice that overexpress Mafb in podocytes using the nephrin promoter/enhancer. To examine a potential pathogenetic role for Mafb in diabetic nephropathy, Mafb transgenic mice were treated with either streptozotocin or saline solution. Diabetic nephropathy was assessed by renal histology and biochemical analyses of urine and serum. Podocyte-specific overexpression of Mafb had no effect on body weight or blood glucose levels in either diabetic or control mice. Notably, albuminuria and changes in BUN levels and renal histology observed in diabetic wild-type animals were ameliorated in diabetic Mafb transgenic mice. Moreover, hyperglycemia-induced downregulation of Nephrin was mitigated in diabetic Mafb transgenic mice, and reporter assay results suggested that Mafb regulates Nephrin directly. Mafb transgenic glomeruli also overexpressed glutathione peroxidase, an antioxidative stress enzyme, and levels of the oxidative stress marker 8-hydroxydeoxyguanosine decreased in the urine of diabetic Mafb transgenic mice. Finally, Notch2 expression increased in diabetic glomeruli, and this effect was enhanced in diabetic Mafb transgenic glomeruli. These data indicate Mafb has a protective role in diabetic nephropathy through regulation of slit diaphragm proteins, antioxidative enzymes, and Notch pathways in podocytes and suggest that Mafb could be a therapeutic target.
Concanavalin A-binding cholesterol crystallization inhibiting and promoting activity in bile from patients with Crohn's disease compared to patients with ulcerative colitis
Authors: Yolande C.A Keulemans, Kam S Mok, J.Frederik M Slors, Menno A Brink, Dirk J Gouma, Guido N.J Tytgat, Albert K Groen
Journal: Journal of Hepatology (1999)
REDOX REGULATION BY INTRINSIC SPECIES AND EXTRINSIC NUTRIENTS IN NORMAL AND CANCER CELLS
Authors: Archana Jaiswal McEligot, Sun Yang, Frank L. Meyskens, Jr.
Journal: Annual Review of Nutrition (2005)

Cells in multicellular organisms are exposed to both endogenous oxidative stresses generated metabolically and to oxidative stresses that originate from neighboring cells and from other tissues. To protect themselves from oxidative stress, cells are equipped with reducing buffer systems (glutathione/GSH and thioredoxin/thioredoxin reductase) and have developed several enzymatic mechanisms against oxidants that include catalase, superoxide dismutase, and glutathione peroxidase. Other major extrinsic defenses (from the diet) include ascorbic acid, beta-carotene and other carotenoids, and selenium. Recent evidence indicates that in addition to their antioxidant function, several of these redox species and systems are involved in regulation of biological processes, including cellular signaling, transcription factor activity, and apoptosis in normal and cancer cells. The survival and overall well-being of the cell is dependent upon the balance between the activity and the intracellular levels of these antioxidants as well as their interaction with various regulatory factors, including Ref-1, nuclear factor-kappaB, and activating protein-1.
Histopathological Lung Changes in Children due to Biomass Fuel
Authors: María Alejandra Mena, Fernando Woll, Jaime Cok, Juan Carlos Ferrufino, Roberto Alfonso Accinelli
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Three billion people use biomass fuel worldwide, and up to 2million deaths are attributed to its exposure each year (1). In Peru, over 9 million people use biomass fuel, and in developing countries, biomass fuel exposure is the fourth highest risk factor for disease (2). In this letter, we describe the histopathological findings in the lungs of four children who died nearly four decades ago from accidental causes and resided in homes in which biomass fuel was used. At that time in Peru, children less than 5 years old spent on average 4–5 hours a day inside the kitchen with their mothers. At the time of death, these children underwent a detailed necroscopy in our institute (4,340 m above sea level). Lung tissue sections from the preserved paraffin blocks generated during those necroscopies were stained with hematoxylin and eosin and examined by a pathologist unaware of the clinical data associated with these children. The pathologist scored lung sections from the four children according to the criteria described in Table 1. Macrophages with anthracotic pigment were found in the alveoli and in the septum of all four children (Table 1 and Figure 1). In three of the four children, we found changes compatible with bronchitis (1). We found no evidence for caliciform cell metaplasia or a positive Reid’s index (.0.4) in any of the children. Mild emphysema was noted in a girl of 1 year and 2 months. In adults, exposure to biomass fuel has been associated with the changes we observed in children as well as septal enlargement, fibrosis, bronchitis, glandular hyperplasia, and goblet cell metaplasia (3–6). We suggest that the changes we observed in these children represent the earliest changes associated with biomass fuel–induced lung disease.
Impaired Cerebral Autoregulation in Patients With Malignant Hypertension
Authors: Rogier V. Immink, Bert-Jan H. van den Born, Gert A. van Montfrans, Richard P. Koopmans, John M. Karemaker, Johannes J. van Lieshout
Journal: Circulation (2004)

Background— In patients with a malignant hypertension, immediate parenteral treatment with blood pressure–lowering agents such as intravenous sodium nitroprusside (SNP) is indicated. In this study, we evaluated static and dynamic cerebral autoregulation (CA) during acute blood pressure lowering with SNP in these patients. Methods and Results— In 8 patients with mean arterial pressure (MAP) &gt;140 mm Hg and grade III or IV hypertensive retinopathy at hospital admission, middle cerebral artery blood velocity (MCA V) and blood pressure were monitored. Dynamic CA was expressed as the 0.1-Hz MCA V mean to MAP phase lead and static CA as the MCA V mean to MAP relationship during SNP treatment. Eight normotensive subjects served as a reference group. In the patients, the MCA V mean to MAP phase lead was lower (30±8° versus 58±5°, mean±SEM; P &lt;0.05), whereas the transfer gain tended to be higher. During SNP treatment, target MAP was reached within 90 minutes in all patients. The MCA V mean decrease was 22±4%, along with a 27±3% reduction in MAP (from 166±4 to 121±6 mm Hg; P &lt;0.05) in a linear fashion (averaged slope, 0.82±0.15% cm · s −1 · % mm Hg −1 ; r =0.70±0.07). Conclusions— In patients with malignant hypertension, dynamic CA is impaired. An MCA V mean plateau was not detected during the whole SNP treatment, indicating loss of static CA as well. This study showed that during the whole rapid reduction in blood pressure with SNP, MCA V mean decreases almost one on one with MAP.
Variability of kinematic and kinetic gait data in ambulatory children with spastic cerebral palsy with and without fixed ankle-foot orthoses using 3d motion analysis: a quantitative prospective study
Authors: U Mohammed, R Twycross-Lewis, T Timotijevic, R Woledge, D Bader, M Paterson, D Coggings, D Morrissey
Journal: British Journal of Sports Medicine (2011)

Background Spastic cerebral palsy (SCP) is a common neurological disorder causing inadequate motor-control and functional gait pattern. Fixed ankle-foot orthoses (FAFOs) have become a widespread conservative therapy in SCP. Gait of these children exhibits a large degree of within-child variability but few studies have investigated this variability in terms of kinematics and kinetics and no studies address how this variability is affected with the use of FAFOs. Objectives To compare intrapatient variability of kinematic and kinetic gait parameters between a sample of ambulatory children with SCP and two healthy children with normal gait. The secondary aim was to assess if these variability profiles change in the SCP children as a result of FAFO application. Methods Four SCP and two normal ambulatory children, aged 5–15, were recruited and underwent active instrumented gait analysis over a 6 week period. Variability of a measure was defined as the SD of the measure within one child over several repeated gait trials. Results Variability of sagittal-plane pelvic, hip, knee and ankle range of motion (all p&lt;0.01) and sagittal internal hip and knee extensor moments (both p&lt;0.05) were shown to be consistently greater in SCP than that of age-matched children. AFO application reduces sagittal kinematic variability at the pelvis, knee and ankle (all p&lt;0.05) and variability of sagittal hip and knee moments (both p&lt;0.01). Conclusions Children with SCP exhibit significantly higher kinematic and kinetic variability compared to the normal population. FAFOs have the potential to reduce this variability and functionally improve gait. Future studies should utilise larger sample sizes and stricter inclusion criteria taking into account the differing clinical severities of spasticity, FAFO designs and patterns of CP involvement to ensure these are generalisable findings.
Increased DNA synthesis of uninvolved psoriatic epidermis is maintained in vitro
Authors: K. KRAGBALLE, L. DESJARLAIS, C.L. MARCELO
Journal: British Journal of Dermatology (1985)

Clinically uninvolved psoriatic epidermis shows increased DNA synthesis in vivo. We have studied the DNA synthesis of cultured keratinocytes from uninvolved psoriatic skin. Trypsinized epidermal cells were plated on plastic dishes pre-coated with bovine collagen type I. In initial studies, normal human serum was found to be superior to fetal bovine in supporting the growth of human epidermal keratinocytes. Furthermore, keratinocyte cultures established in the presence of normal human serum produced large keratin proteins (68,000 daltons) indicating that the terminal steps in cell differentiation can occur in vitro. In subsequent experiments keratinocyte cultures were grown in medium supplemented with 10% normal human serum. Confluent cultures of keratinocytes from uninvolved psoriatic epidermis had an increased DNA synthesis determined both as the incorporation of [3H]thymidine and as the autoradiographic labelling index. The DNA synthesis of both normal and psoriatic keratinocyte cultures increased in response to incubation in medium with 10% psoriatic serum. The ability of keratinocytes from uninvolved psoriatic epidermis to maintain an increased DNA synthesis suggests the presence of an inherent defect within the population of epidermal keratinocytes in psoriasis. Such a culture system can be used as an in vitro model for the study of psoriasis.
Hyaluronan and proteoglycans in ovarian follicles
Authors: A Salustri
Journal: Human Reproduction Update (1999)

Proteoglycans are macromolecules formed by a protein backbone to which one or more glycosaminoglycan side chains are co-valently attached. They can be secreted by the cells, retained at the cell surface, or stored in intracellular vacuoles. Hyaluronan is an extremely long glycosaminoglycan which, at variance with other glycosaminoglycans, is released into the extracellular matrix as a free polysaccharide not co-valently linked to a core protein. Both proteoglycans and hyaluronan influence many aspects of cell behaviour by multiple interactions with other molecules. They are involved in matrix formation, cell-cell and cell-matrix adhesion, cell proliferation and migration, and show co-receptor activity for growth factors. Both proteoglycan and hyaluronan synthesis change significantly during ovarian follicle development and atresia. This review describes the structure of these molecules and their possible function in ovarian physiology.
Gastroenterology and Hepatology
Authors: M J L. SMITH
Journal: Gut (2000)

Gastroenterology and Hepatology . Edited by Porro GI. (Pp 780; illustrated.) United Kingdom: McGraw-Hill, 1999. ISBN 0 07709 519 7.

Kurt Isselbacher's foreword to this volume indicates that it was not written for the medical specialist, but rather for the family practitioner and general internist. True, this is not YAMADA. Nevertheless, despite being unreferenced and weighing in at only one quarter of the size of this gold standard text, I believe he is inappropriately modest on behalf of the editors and authors. Although a specialist readership may not have been the primary target, those involved in the daily care of alimentary tract and hepatic diseases will find this book an invaluable addition to the departmental shelves.

The format is that now commonly adopted for digestive disease textbooks—that is, an initial section dealing with presenting clinical …