tbuckley/cabot-search huggingface dataset:
Coronary angiogenesis during long-term hypertension and left ventricular hypertrophy in dogs.
Authors: R J Tomanek, K A Schalk, M L Marcus, D G Harrison
Journal: Circulation Research (1989)

Many studies have documented that during the development of left ventricular hypertrophy (LVH) coronary vascular growth lags behind that of cardiac muscle. To ascertain whether significant growth of coronary resistance vessels occurs with long-standing hypertension and LVH, we studied dogs with Goldblatt (one-kidney, one-clip) hypertension seven months after surgery. Left ventricular minimal coronary vascular resistance (LV MCVR) was derived from adenosine-induced maximal flow measured with 15 microns microspheres. Morphometric data were based on perfuse-fixed hearts arrested in diastole. Hypertension and LVH were associated with a 46% increase in left ventricular weight/body weight ratio (LVH, 6.73 +/- 0.31; control, 4.62 +/- 0.30), no significant change in LV MCVR/100 g, and a reduction in total LV MCVR (LVH, 0.11 +/- 0.02 mm Hg/ml/min; control, 0.15 +/- 0.02 mm Hg/ml/min). Arterial and arteriolar wall/lumen ratios were virtually identical in the two groups. Arteriolar (lumen diameter less than 200 microns) numerical densities (arteriolar profiles/mm2) were also similar for the two groups even when analyzed according to lumen diameter size class and by ventricular location (epimyocardium, midmyocardium, and endomyocardium). Moreover, the relative frequency distribution of any arteriolar size class was similar for both groups. Because MCVR and arteriolar density were normal, this study provides new evidence that angiogenesis during long-term LVH in this model is of sufficient magnitude to enable the cross-sectional area of the coronary resistance vessels to increase in proportion to the increase in left ventricular mass.
Early development of stricturing or penetrating pattern in Crohn's disease is influenced by disease location, number of flares, and smoking but not by NOD2/CARD15 genotype
Authors: E Louis
Journal: Gut (2003)

Crohn's disease is a heterogeneous entity. Disease behaviour, characterised as stricturing, penetrating, or non-stricturing non-penetrating, is a clinically important phenotype as it is associated with complications and need for surgery. It has recently been showed that the behaviour of Crohn's disease changes over the course of the disease.To assess the association between rapid development of a penetrating or stricturing pattern of Crohn's disease and demographic and clinical characteristics as well as NOD2/CARD15 genotype.A total of 163 patients with a firm diagnosis of Crohn's disease and who had non-penetrating non-stricturing disease at diagnosis were studied. Various demographic and clinical characteristics as well as antisaccharomyces cerevisiae antibody status and NOD2/CARD15 genotype were documented in these patients. These characteristics were compared in subgroups of patients according to evolution of disease behaviour five years after diagnosis.Five years after diagnosis there were 110 (67.5%) patients with non- structuring non-penetrating disease, 18 (11%) with stricturing disease, and 35 (21.5%) with penetrating disease. In multivariate analysis, only disease location and number of flares per year were significantly discriminant between the three subgroups (p=0.0009 and 0.0001, respectively). Ileal location of the disease was associated with a stricturing pattern while a high number of flares was associated with a penetrating pattern. Active smoking was also associated with a penetrating pattern compared with a non-stricturing non-penetrating pattern only.Early development of stricturing or penetrating behaviour in Crohn's disease is influenced by disease location, clinical activity of the disease, and smoking habit, but not by NOD2/CARD15 genotype.
An uncommon presentation of a common pathogen
Authors: Tobias Boettler, Lisa Lutz, Nathalie Schmidt, Robert Thimme, Christoph Neumann-Haefelin
Journal: Gut (2015)

A 70-year-old woman presented with severe spasmodic abdominal pain, nausea, recurrent vomiting and mild diarrhoea. Two months earlier she underwent autologous stem cell transplantation for stage 2A follicular lymphoma. Her medical history was otherwise unremarkable. Physical examination revealed mild epigastric tenderness. Blood tests showed an elevated lactate dehydrogenase (325 IU/L; normal range 135–214 IU/L) and elevated transaminases (alanine transaminase 126 IU/L; aspartate transaminase 90 IU/L; normal range 10–35 IU/L). Blood cell counts were within the normal range. Ultrasound examination did not detect a cause for the abdominal pain. She was not on immunosuppressive therapy.

Subsequently, the patient underwent upper endoscopy that revealed the presence of several protruding, ulcerative …
Changes in myoplasmic sodium concentration during exposure to lactate in perfused rat heart
Authors: S E Turvey, D G Allen
Journal: Cardiovascular Research (1994)

The free myoplasmic sodium concentration ([Na+]i) is thought to change during acidosis and ischaemia in the mammalian heart. Although there are methods available for measuring [Na+]i in isolated cells or small preparations, none is very effective in the isolated heart, which is one of the best models for studying ischaemia. The use of a fluorescent sodium indicator, sodium binding benzofuran isophthalate (SBFI), to measure [Na+]i in the isolated, perfused rat heart is described. This method was used to estimate the activity of the Na/H exchanger under conditions resembling some aspects of ischaemia.The acetoxymethyl ester of SBFI was loaded into the perfused rat heart via the perfusate. Fluorescence signals developed on loading and were shown to be [Na+]i sensitive. An in vivo calibration technique allowed the fluorescence signals to be converted to [Na+]i.The [Na+]i under control conditions was 6.4 mM. When the hearts were exposed to 20 mM lactate at the normal extracellular pH (pHo = 7.4) for 10 min, developed pressure fell abruptly and then slowly recovered [Na+]i rose slowly by 1.5 mM during lactate exposure and paralleled the recovery of pressure. Exposure to lactate at reduced extracellular pH (pHo = 6.4) produced a larger rise in [Na+]i. In the presence of the Na/H exchange inhibitor 5-(N-methyl-N-isobutyl)-amiloride exposure to lactate caused a small fall in [Na+]i at pHo 7.4 and 6.4.The advantages and disadvantages of SBFI as an [Na+]i indicator in the perfused heart are described. The Na/H exchanger is an important regulator of [Na+]i during lactate induced intracellular acidosis, and it remains active in the presence of a substantial extracellular acidosis. This shows that low pHo does not necessarily inhibit the Na/H exchanger. The use of SBFI to estimate [Na+]i in the perfused heart is novel and has considerable potential for studies of ischaemia and related conditions.
Does expiratory flow limitation predict chronic dyspnoea in adults with cystic fibrosis?
Authors: A. E. Holland, L. Denehy, J. W. Wilson
Journal: European Respiratory Journal (2006)

Tidal expiratory flow limitation (EFL) may promote dynamic hyperinflation and contribute to chronic dyspnoea. The purpose of this study was to assess the contribution of EFL to chronic dyspnoea in adults with cystic fibrosis (CF). The presence of EFL was determined in 102 adults with stable CF (forced expiratory volume in one second (FEV1) 17.3-91.5% predicted) and 20 age-matched control subjects using the negative expiratory pressure technique. Measurements of inspiratory capacity (IC) and spirometry were performed, and chronic dyspnoea was evaluated using the modified Medical Research Council scale. EFL was present in 34 subjects (33%), with 18 subjects flow limited in the sitting position and 16 subjects flow limited only in the supine position. Flow limitation in the sitting position was associated with older age and lower FEV1 compared with flow-limited supine position and non-flow-limited subjects. A significant reduction in IC accompanied EFL in both the sitting and supine positions. Flow limitation in the sitting position was associated with significantly higher levels of chronic dyspnoea. Ordinal regression analysis indicated that EFL was the best predictor of chronic dyspnoea in a model that included FEV1 % pred. Expiratory flow limitation in cystic fibrosis is associated with reduced forced expiratory volume in one second, older age and dynamic hyperinflation. Expiratory flow limitation significantly contributes to chronic dyspnoea in cystic fibrosis.
The Relationships of pfs, pps and Tumor Response with Os in Patients with Nsclc Treated with Gefitinib as First-Line
Authors: Reiko Yoshino, Hisao Imai, Yoshio Tomizawa, Kousuke Takei, Mai Tomizawa, Akihiro Yoshii, Satoru Watanabe, Ryusei Saitou, Masanobu Yamada
Journal: Annals of Oncology (2014)
Hormonal Manipulations May Also Reduce Breast Cancer Risk
Authors: N. J. Nelson
Journal: JNCI Journal of the National Cancer Institute (1999)

At the City of Hope National Medical Center in Duarte California a group of researchers are testing a contraceptive strategy to prevent endometrial ovarian and breast cancers.  A phase I trial is being conducted among a small group of high-risk premenopausal women most with BRCA1 mutations.  Its primary endpoint is reduction of mammographic density to make the detection of asymptomatic cancers easier.  The strategy is to block a womans hormone production and then add back estrogen and progestogen to a level seen in postmenopausal women on estrogen replacement therapy.  The actual protocol calls for a daily nasal spray containing deslorelin and adding back daily low doses of estradiol and testosterone by either nasal spray or patch.  In addition progestin is taken orally every 3 months to protect against endometrial cancer.  Indirect evidence indicates that this strategy might work.  A 1994 study found that women (ages 25-40) with a high risk for breast cancer taking a combination of an agonist with added-back estrogen and progesterone showed a significant reduction in mammographic density.  However there is a need for caution with the agonist regimen: the long-term effects of deslorelin a gonadotropin-releasing hormone agonist and testosterone are unknown.  A large controlled phase III trial is needed to provide answers.
Imaging of the hypoxia-inducible factor pathway: insights into oxygen sensing
Authors: U Berchner-Pfannschmidt, S Frede, C Wotzlaw, J Fandrey
Journal: European Respiratory Journal (2008)

The transcription factor complex hypoxia-inducible factor (HIF)-1 controls the expression of most genes involved in adaptation to hypoxic conditions. HIF-1 is a heterodimer composed of oxygen-labile HIF-α and constitutively expressed HIF-β subunits. The oxygen-dependent regulation of HIF-α is a multistep process that includes degradation under normoxia but stabilisation, translocation into the nucleus and activation under hypoxic conditions. The present paper summarises the contributions of optical methods to the understanding of oxygen-dependent regulation of the HIF-1 pathway. The tissue- and cell-specific distribution of HIF-α was visualised immunohistochemically and by immunofluorescence. Transcriptional activity of HIF-1 was monitored using green fluorescent protein as a reporter under control of hypoxia response elements in living cells, spheroids and tumour tissues in living mice. With cyan and yellow variants of green fluorescent protein fused to HIF subunits and regulatory proteins, subcellular distribution, migration and interaction were imaged in vivo by means of fluorescence recovery after photo-bleaching and fluorescence resonance energy transfer. Noninvasive imaging of these cellular and molecular processes by laser scanning microscopy complements ex vivo molecular biology assays and provides an additional spatial and temporal dimension to the understanding of the HIF-1 pathway.
Protective effect of the lazaroid U74006F in cold ischemia-reperfusion injury of the liver
Authors: Carlos A. Cosenza, Donald V. Cramer, Scott A. Cunneen, Phillip J. Tuso, Hong K. Wang, Leonard Makowka
Journal: Hepatology (1994)

Lipid peroxidation may play a major role in the loss of liver graft viability after prolonged cold ischemia and reperfusion injury. The lazaroid compound U74006F is a potent inhibitor of lipid peroxidation, and this study was designed to evaluate the efficacy of this compound in preventing cold ischemia–reperfusion damage in three different models: pig endothelial cells in culture, ex vivo isolated pig liver perfusion and orthotopic transplantation of syngeneic rat livers. The addition of U74006F to University of Wisconsin preservation solution significantly prolonged endothelial cell viability after 48 and 72 hr of cold ischemia and reoxygenation (p < 0.01). Donor pigs were injected with vehicle or U74006F (4.5 mg/kg) before liver harvest. After 24 hr of cold storage in University of Wisconsin solution, the livers were perfused with pig blood for 180 min in an isolation chamber. Measurements of liver function parameters, including AST, ALT, bile production, superoxide anion and phospholipase A2 release, were assessed every 60 min. Although bile production was similar in the U74006F-treated and control groups, significant decreases of AST and ALT levels (p < 0.01) in the perfusate of the livers from treated donors were observed. In addition, the U74006F group displayed significantly reduced release of superoxide anion and phospholipase A2 compared with these parameters in the untreated group (p < 0.05 and p < 0.01, respectively). In the last model, donor rats were treated with U74006F before harvest; the rat liver grafts were preserved in cold University of Wisconsin solution for 24 hr and then transplanted into recipient rats. The number of liver graft recipients that survived 7 days after transplantation was significantly larger (p < 0.001) in the group of recipients of U74006F-treated livers. Furthermore, this group showed significantly lower levels of lipid peroxides in liver tissues (p < 0.01) and AST and ALT release (p < 0.05) compared with the control group at 2 and 7 days after transplantation. We conclude that U74006F is effective in enhancing the resistance of the liver to damage due to cold ischemia–reperfusion injury and that the use of this compound may improve early liver graft function after transplantation. (Hepatology 1994;19:418–425).
Thiazide Diuretics Directly Induce Osteoblast Differentiation and Mineralized Nodule Formation by Interacting with a Sodium Chloride Co-Transporter in Bone
Authors: Melita M. Dvorak, Cyrille De Joussineau, D. Howard Carter, Trairak Pisitkun, Mark A. Knepper, Gerardo Gamba, Paul J. Kemp, Daniela Riccardi
Journal: Journal of the American Society of Nephrology (2007)

Thiazide diuretics are used worldwide as a first-choice drug for patients with uncomplicated hypertension. In addition to their antihypertensive effect, thiazides increase bone mineral density and reduce the prevalence of fractures. Traditionally, these effects have been attributed to increased renal calcium reabsorption that occurs secondary to the inhibition of the thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule. The aim of the current study was to determine whether thiazides exert a direct bone-forming effect independent of their renal action. We found that the osteoblasts of human and rat bone also express NCC, suggesting that these bone-forming cells may be an additional target for thiazides. In vitro, NCC protein was virtually absent in proliferating human and fetal rat osteoblasts, whereas its expression dramatically increased during differentiation. Thiazides did not affect osteoblast proliferation, but directly stimulated the production of the osteoblast differentiation markers runt-related transcription factor 2 (runx2) and osteopontin. Using overexpression/knockdown studies in fetal rat calvarial cells, we show that thiazides increase the formation of mineralized nodules, but loop diuretics do not. Overall, our study demonstrates that thiazides directly stimulate osteoblast differentiation and bone mineral formation independent of their effects in the kidney. Therefore, in addition to their use as antihypertensive drugs, our results suggest that thiazides may find a role in the prevention and treatment of osteoporosis.
Wash-out kinetics and efficacy of a modified lavage technique for alveolar proteinosis
Authors: Francesco Bonella, Peter C. Bauer, Matthias Griese, Thomas E. Wessendorf, Josune Guzman, Ulrich Costabel
Journal: European Respiratory Journal (2012)

Whole lung lavage (WLL) is the standard treatment for pulmonary alveolar proteinosis (PAP). This study aimed to provide data about the kinetics of the protein wash-out, to identify factors influencing the protein concentration in the recovered fluid and to assess the efficacy of a modified lavage technique. Samples of 180 WLLs from 42 adult PAP patients were collected. 110 WLLs were performed according to the classical technique. In 70 WLLs, repeated manual ventilation was applied during the procedure. Spectrophotometry was used to measure the protein concentration in the recovered fluid. The initial protein concentration in the recovered fluid was 460 mg·dL −1 , the final concentration was 26 mg·dL −1 and the total amount of removed proteins during a lavage was 17.5 g. A history of dust exposure was associated with a higher residual protein concentration in the recovered fluid (p=0.000013). The amount of removed proteins correlated inversely with the diffusing capacity of the lung for carbon monoxide (p=0.001) and oxygen tension (p=0.004). The modified technique removed a greater amount of proteins than the classical technique and prolonged the time to relapse (p=0.011). Exposure to dust seems to influence the kinetics of the protein wash-out. Applying manual ventilation during the procedure can enhance the efficacy of WLL.
Mortality during hospitalisation for pneumonia in Alberta, Canada, is associated with physician volume
Authors: T.J. Marrie, K.C. Carriere, Y. Jin, D.H. Johnson
Journal: European Respiratory Journal (2003)

<h3>ABSTRACT</h3> During the first 3 months of 2020, as the COVID-19 pandemic developed, it was noticed that requests from primary care for investigations were decreasing, including those that form part of the diagnostic process for cancers. We therefore obtained data on the requests from primary care for chest X-rays (CXRs) and CA125 measurement our hospital received in the first half of 2020 and compared them with 2019. The number of CXRs declined by 93% in April 2020 compared with 2019, with the decline being greater for patient living in outlying areas. Requests from the emergency department also declined. Requests for CA125 measurement similarly fell by 77% from all areas. The requests increased in June, CA125 more than CXR. If this phenomenon is widespread it may have an impact on diagnosis of major conditions, particularly cancers and tuberculosis.
Non-dietary lipid in the intestinal lumen
Authors: P. B. Cotton
Journal: Gut (1972)

Lipid in the intestinal lumen is mainly dietary in origin, but there is also an endogenous component from bile, bacteria, and the mucosa (through exudation and cell loss). Perfusion experiments in fasting rats demonstrate that exfoliated cells carry with them into the small intestinal lumen an average of 1.12 mg lipid/30 minutes; lipid classes consisting of phosphatidyl choline (lecithin), triglyceride, cholesterol, cholesterol ester, phosphatidyl ethanolamine, and free fatty acid. Fatty acid also enters the lumen independently of cells by exudation. Since the rate of lipid exfoliation and exudation considerably exceeds the faecal lipid excretion in fasting rats, efficient reabsorption must normally occur. Calculations based on published data suggest the daily exfoliation of 12 to 30 g lipid into the small intestinal lumen of fasting man. When reabsorption is impaired, especially in states of increased cell turnover, endogenous mucosal lipid may account for a significant proportion of faecal lipid, perhaps sufficient to constitute a state of fat-losing enteropathy.
Pterostilbene, an Active Constituent of Blueberries, Suppresses Aberrant Crypt Foci Formation in the Azoxymethane-Induced Colon Carcinogenesis Model in Rats
Authors: Nanjoo Suh, Shiby Paul, Xingpei Hao, Barbara Simi, Hang Xiao, Agnes M. Rimando, Bandaru S. Reddy
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Epidemiologic studies have linked the consumption of fruits and vegetables to reduced risk of several types of cancer. Laboratory animal model studies have provided evidence that stilbenes, phenolic compounds present in grapes and blueberries, play a role in inhibiting the risk of certain cancers. Pterostilbene, a naturally occurring stilbene from blueberries, was tested for its preventive activity against colon carcinogenesis. Experimental Design: Experiments were designed to study the inhibitory effect of pterostilbene against the formation of azoxymethane-induced colonic aberrant crypt foci (ACF) preneoplastic lesions in male F344 rats. Beginning at 7 weeks of age, rats were treated with azoxymethane (15 mg/kg body weight s.c., once weekly for 2 weeks). One day after the second azoxymethane treatment, rats were fed experimental diets containing 0 or 40 ppm of pterostilbene. At 8 weeks after the second azoxymethane treatment, all rats were sacrificed, and colons were evaluated for ACF formation and for inhibition of inducible nitric oxide synthase (iNOS) and proliferating cell nuclear antigen. Effects on mucin MUC2 were also determined. Results: Administration of pterostilbene for 8 weeks significantly suppressed azoxymethane-induced formation of ACF (57% inhibition, P &amp;lt; 0.001) and multiple clusters of aberrant crypts (29% inhibition, P &amp;lt; 0.01). Importantly, dietary pterostilbene also suppressed azoxymethane-induced colonic cell proliferation and iNOS expression. Inhibition of iNOS expression by pterostilbene was confirmed in cultured human colon cancer cells. Conclusions: The results of the present study suggest that pterostilbene, a compound present in blueberries, is of great interest for the prevention of colon cancer.