tbuckley/cabot-search huggingface dataset:
Reperfusion injury induces apoptosis in rabbit cardiomyocytes.
Authors: R A Gottlieb, K O Burleson, R A Kloner, B M Babior, R L Engler
Journal: Journal of Clinical Investigation (1994)

The most effective way to limit myocardial ischemic necrosis is reperfusion, but reperfusion itself may result in tissue injury, which has been difficult to separate from ischemic injury. This report identifies elements of apoptosis (programmed cell death) in myocytes as a response to reperfusion but not ischemia. The hallmark of apoptosis, nucleosomal ladders of DNA fragments (approximately 200 base pairs), was detected in ischemic/reperfused rabbit myocardial tissue but not in normal or ischemic-only rabbit hearts. Granulocytopenia did not prevent nucleosomal DNA cleavage. In situ nick end labeling demonstrated DNA fragmentation predominantly in myocytes. The pattern of nuclear chromatin condensation was distinctly different in reperfused than in persistently ischemic tissue by transmission electron microscopy. Apoptosis may be a specific feature of reperfusion injury in cardiac myocytes, leading to late cell death.
Better 5-year survival of fibrolamellar hepatocellular carcinoma versus conventional hepatocellular carcinoma: still too close to call: Table 1
Authors: Basile Njei
Journal: Gut (2014)

We read with great interest the letter by Eggert et al , in response to our recently published article which raised concerns about the better 5-year survival of fibrolamellar hepatocellular carcinoma (fHCC) compared with conventional hepatocellular carcinoma (HCC-NOS).1 ,2 In the letter, the authors pointed out that it cannot be concluded from our meta-analysis that ‘survival in fHCC is similar to conventional HCC in non-cirrhotic liver patients’, given the overlap in the CIs of the subgroup analyses (limited to non-cirrhotic liver patients) and the overall analysis of all cases. The authors further report findings of their recently published follow-up article …
Effect of statin therapy in patients with lung cancer on mortality, incidence of infections and pulmonary embolism
Authors: Stefan Krüger, Annika Vehl, Angelika Haselhuhn, Dirk Frechen
Journal: European Respiratory Journal (2012)

Background:  Statins (S) have antiproliferative effects. Aim of this study was to assess whether S users with lung cancer (LC) had reduced risk of mortality, infections and pulmonary embolism.   Methods:  We studied the association of S use in a retrospective study in 465 pts with first diagnosis of LC. The primary variables were stage and type of LC and S use at time of LC diagnosis and thereafter. During follow-up occurrence of death, infections and pulmonary embolism were recorded.   Results:  91 pts (19.6%) had S, 371 pts not. LC stages were I-IIIA 201 pts (43.2%), IIIb-IV 264 pts (56.8%). Pts with S were older (67.8 ± 7.6 vs. 64.5 ± 9.8 y., p    Conclusions:  Long-term S therapy seems to reduce mortality in younger LC pts
Expression of beta 1-integrins on activated mesangial cells in human glomerulonephritis.
Authors: T Kuhara, S Kagami, Y Kuroda
Journal: Journal of the American Society of Nephrology (1997)

beta 1-integrins, a family of cell-surface receptors, mediate cell-matrix interactions that play a critical role in tissue development and tissue remodeling after injury. In this study, to clarify the importance of beta 1-integrins in human glomerulonephritis (GN), the relationship among the glomerular expression of beta 1-integrins, their ligand matrix components, alpha-smooth muscle actin (alpha-SM actin) as a marker of activated mesangial cells (MC), transforming growth factor-beta (TGF-beta), and glomerular cellularity in two normal kidneys, ten minimal change nephrotic syndrome, 23 immunoglobulin A (IgA) GN, 13 lupus GN, and four membranous GN kidneys were studied. Immunostaining was performed on frozen sections, using monoclonal anti-alpha-SM actin antibody and polyclonal antibodies against fibronectin, collagen type IV, laminin, each subunit of alpha 1 beta 1 (collagen/laminin receptor), alpha 5 beta 1 (fibronectin receptor) and TGF-beta. Quantitation of staining indicated that the glomerular expression of alpha 1 beta 1 and alpha 5 beta 1 integrins correlated with the mesangial amounts of their ligands, collagen type IV, laminin and fibronectin (P < 0.01), alpha-SM actin (P < 0.01), and TGF-beta (P < 0.01). In addition, a correlation was observed between an increased expression of alpha 1 beta 1 and alpha 5 beta 1 integrins and the degree of glomerular cell proliferation (P < 0.01). Double immunostaining showed that activated MC expressing alpha-SM actin strongly expressed alpha 1 beta 1 and alpha 5 beta 1 integrins, and these MC phenotypic alterations paralleled the level of glomerular TGF-beta staining (P < 0.01). In conclusion, enhanced expression of beta 1-integrins by activated MC may contribute to the pathological mesangial remodeling characterized by MC proliferation and matrix deposition in human GN. Increased glomerular TGF-beta appears to be involved in these MC phenotypic changes.
Elevated Blood Pressure in Transgenic Mice With Brain-Specific Expression of Human Angiotensinogen Driven by the Glial Fibrillary Acidic Protein Promoter
Authors: Satoshi Morimoto, Martin D. Cassell, Terry G. Beltz, Alan Kim Johnson, Robin L. Davisson, Curt D. Sigmund
Journal: Circulation Research (2001)

In addition to the circulatory renin (REN)–angiotensin system (RAS), a tissue RAS having an important role in cardiovascular function also exists in the central nervous system. In the brain, angiotensinogen (AGT) is expressed in astrocytes and in some neurons important to cardiovascular control, but its functional role remains undefined. We generated a transgenic mouse encoding the human AGT (hAGT) gene under the control of the human glial fibrillary acidic protein (GFAP) promoter to experimentally dissect the role of brain versus systemically derived AGT. This promoter targets expression of transgene products to astrocytes, the most abundant cell type expressing AGT in brain. All transgenic lines exhibited hAGT mRNA expression in brain, with variable expression in other tissues. In one line examined in detail, transgene expression was high in brain and low in tissues outside the central nervous system, and the level of plasma hAGT was not elevated over baseline. In the brain, hAGT protein was mainly localized in astrocytes, but was present in neurons in the subfornical organ. Intracerebroventricular (ICV) injection of human REN (hREN) in conscious unrestrained mice elicited a pressor response, which was abolished by ICV preinjection of losartan. Double-transgenic mice expressing the hREN gene and the GFAP-hAGT transgene exhibited a 15–mm Hg increase in blood pressure and an increased preference for salt. Blood pressure in the hREN/GFAP-hAGT mice was lowered after ICV, but not intravenous losartan. These studies suggest that AGT synthesis in the brain has an important role in the regulation of blood pressure and electrolyte balance.
Prevalence of sexually transmitted disease among male patients presenting with proctitis.
Authors: H Andrews, J Wyke, M Lane, J Clay, M R Keighley, R N Allan
Journal: Gut (1988)

Fifty male patients with proctitis were examined and the clinical, microbiological, serological and proctological features compared with 51 known male homosexuals attending the genitourinary (GU) clinic at the same hospital. The homosexuals had a short history of bowel symptoms, minor sigmoidoscopic and histological changes on rectal biopsy and many positive serological markers of sexually transmitted infection. There was some evidence of sexually transmitted disease in the IBD patients and three were homosexuals. IgG antibodies were positive for chlamydia trachomatis (n = 10) and hepatitis A (n = 7). One had a positive screening test for syphilis. Stool examination and rectal swab cultures were positive in two patients for cryptosporidium and cytomegalovirus respectively. Gastroenterologists must be aware of the possibility of specific infection in IBD patients and a clinical history should include sexual preferences and practices. If homosexuality is admitted, specific infection must be sought and excluded.
Coculture of human liver macrophages and cholangiocytes leads to CD40-dependent apoptosis and cytokine secretion
Authors: Edward B. Alabraba, Vincent Lai, Louis Boon, Stephen J. Wigmore, David H. Adams, Simon C. Afford
Journal: Hepatology (2007)

In the vanishing bile duct syndromes (VBDS), primary biliary cirrhosis and chronic allograft rejection, cholangiocyte apoptosis is associated with sustained macrophage infiltration of the liver, suggesting that these cells may mediate tissue damage and contribute to bile duct destruction. We have previously reported that activation of CD40 on cholangiocytes with either soluble CD154 or cross-linking monoclonal antibody to CD40 induces apoptosis in vitro. We have now developed a novel primary human cell coculture model and used it to investigate (1) how macrophages kill cholangiocytes; (2) how paracrine cell interactions can shape the local cytokine milieu within the liver. We report that lipopolysaccharide (LPS) and interferon (IFN) induce sustained expression of CD154 on liver-derived macrophages (LDM) in vitro. Coculture of activated LDM expressing high levels of CD154 (CD40 ligand) with human cholangiocytes resulted in (1) CD40-dependent secretion of proinflammatory cytokines; (2) apoptosis of cholangiocytes that was abolished by antagonistic antibodies directed against human CD40 or human CD154.Macrophages are important effector cells in bile duct destruction in VBDS, and this role is dependent on CD40-mediated mechanisms. Thus activation of CD40 on cholangiocytes by activated macrophages provides a molecular mechanism to amplify chronic inflammation and bile duct destruction in liver disease. These data suggest that effective targeting strategies to antagonize CD40/CD154 may have beneficial effects in patients suffering from the VBDS.
Comparison of Glycemic and Lipid Response to Pioglitazone Treatment in Mexican-Americans and Non-Hispanic Caucasians With Type 2 Diabetes
Authors: Allen B. King, Dana U. Armstrong, Sithiphol Chinnapongse
Journal: Diabetes Care (2003)

The risk of type 2 diabetes in Mexican-Americans is almost twice that of non-Hispanic Caucasians (1). Mexican-Americans are also, in general, more likely to have insulin resistance, impaired fasting glucose, and impaired glucose tolerance than non-Hispanic Caucasians (1,2). Given these increased risks of type 2 diabetes in the Mexican-American population and the fact that poor glycemic control is more common in diabetic Mexican-Americans than in non-Hispanic Caucasians (3), it is important to consider the efficacy of diabetes therapy in this specific population.

In a retrospective chart review, our clinic identified patients with type 2 diabetes who had been treated with pioglitazone 45 mg/day for 6 or more months without interruption. Patient charts were then selected if HbA1c and lipids were available within 4 weeks of starting treatment and ∼4 months into treatment. Patients whose lipid-lowering medication was changed during this same time period were excluded. In total, data from …
FasL autoantibodies in vasculitis are associated with the presence of anticorneal epithelial antibodies
Authors: E Gowen
Journal: Annals of the Rheumatic Diseases (2002)

Eye complications are common in vasculitis, especially in Wegener's granulomatosis (WG), where up to 50% of all cases have ophthalmic involvement. Eye involvement in the Churg-Strauss syndrome (CSS) has been reported but is rare. Corneal autoantigens have been documented in patients with WG and CSS; in particular, circulating autoantibodies to corneal specific keratin 3 (K3) are present in 60% of patients with WG.1 Most of these patients have peripheral ulcerative keratitis (PUK), but others have no detectable eye disease. Antibodies to a second corneal antigen, BCEA-B, are associated with CSS.2

The eye is an immune privileged organ characterised by a reduced or modified immune response which protects the eye from inflammation and autoimmunity. Fas, together with its ligand FasL, has an important role in maintaining ocular immune privilege. Fas+ lymphoid cells that enter the eye are killed by apoptosis when the Fas binds …
Switch from systemic steroids to budesonide in steroid dependent patients with inactive Crohn's disease
Authors: A Cortot
Journal: Gut (2001)

<h3>BACKGROUND</h3> Steroid dependent patients with Crohn9s disease are at high risk of developing glucocorticosteroid induced side effects. <h3>AIMS</h3> We evaluated the possibility of switching from systemic steroids to budesonide (Entocort) in prednisolone/prednisone dependent patients with inactive Crohn9s disease affecting the ileum and/or ascending colon. <h3>PATIENTS</h3> Steroid dependent patients with a Crohn9s disease activity index ⩽200 were included. <h3>METHODS</h3> In a double blind multicentre trial, 120 patients were randomly assigned to receive budesonide 6 mg once daily or placebo. Prednisolone was tapered to zero during the first 4–10 weeks and budesonide or placebo was given concomitantly and for a further 12 weeks. Relapse was defined as an index &gt;200 and an increase of 60 points from baseline or withdrawal due to disease deterioration. <h3>RESULTS</h3> After one and 13 weeks without prednisolone, relapse rates were 17% and 32%, respectively, in the budesonide group, and 41% and 65% in the placebo group (95% confidence intervals for the difference in percentages −41%, −8% and −51%, −16%; p=0.004 and p&lt;0.001, respectively). The number of glucocorticosteroid side effects was reduced by 50% by switching from prednisolone and was similar in the budesonide and placebo groups. Basal plasma cortisol increased in both groups. <h3>CONCLUSIONS</h3> The majority of patients with steroid dependent ileocaecal Crohn9s disease may be switched to budesonide controlled ileal release capsules 6 mg without relapse, resulting in a sharp decrease in glucocorticosteroid side effects similar to placebo, and with an increase in plasma cortisol levels.
Prediction of peak flow values followed by feedback improves perception of lung function and adherence to inhaled corticosteroids in children with asthma
Authors: Jonathan M Feldman, Haley Kutner, Lynne Matte, Michelle Lupkin, Dara Steinberg, Kimberly Sidora-Arcoleo, Denise Serebrisky, Karen Warman
Journal: Thorax (2012)

<h3>Background</h3> Failure to detect respiratory compromise can lead to emergency healthcare use and fatal asthma attacks. The purpose of this study was to examine the effect of predicting peak expiratory flow (PEF) and receiving feedback on perception of pulmonary function and adherence to inhaled corticosteroids (ICS). <h3>Methods</h3> The sample consisted of 192 ethnic minority, inner-city children (100 Puerto Rican, 54 African-American, 38 Afro-Caribbean) with asthma and their primary caregivers recruited from outpatient clinics in Bronx, New York. Children9s PEF predictions were entered into an electronic spirometer and compared with actual PEF across 6 weeks. Children in one study were blinded to PEF (n=88; no feedback) and children in a separate study were able to see PEF (n=104; feedback) after predictions were locked in. Dosers were attached to asthma medications to monitor use. <h3>Results</h3> Children in the feedback condition displayed greater accuracy (p&lt;0.001), less under-perception (p&lt;0.001) and greater over-perception (p&lt;0.001) of respiratory compromise than children in the no feedback condition. This between-group difference was evident soon after baseline training and maintained across 6 weeks. The feedback condition displayed greater adherence to ICS (p&lt;0.01) and greater quick-relief medication use (p&lt;0.01) than the no feedback condition. <h3>Conclusions</h3> Feedback on PEF predictions for ethnic minority, inner-city children may decrease under-perception of respiratory compromise and increase adherence to controller medications. Children and their families may shift their attention to asthma perception and management as a result of this intervention.
Circulating Levels of Soluble KIT Serve as a Biomarker for Clinical Outcome in Gastrointestinal Stromal Tumor Patients Receiving Sunitinib following Imatinib Failure
Authors: Samuel E. DePrimo, Xin Huang, Martin E. Blackstein, Christopher R. Garrett, Charles S. Harmon, Patrick Schöffski, Manisha H. Shah, Jaap Verweij, Charles M. Baum, George D. Demetri
Journal: Clinical Cancer Research (2009)

To evaluate changes in circulating levels of soluble KIT (sKIT) extracellular domain as a potential biomarker for clinical outcome in gastrointestinal stromal tumor patients treated with the multitargeted tyrosine kinase inhibitor sunitinib following imatinib failure in a previously reported phase III study.Patients received sunitinib 50 mg/d (n = 243) or placebo (n = 118) daily in 6-week cycles (4 weeks on, 2 weeks off treatment). Plasma sKIT levels were sampled every 2 weeks in cycle 1 and on days 1 and 28 of subsequent cycles; analyzed by ELISA; and evaluated using Prentice criteria, Cox proportional hazards models, and proportion of treatment effect (PTE) analysis.From 4 weeks on treatment and onward, significant differences were shown between treatment groups (P < 0.0001) in sKIT level changes from baseline (median levels decreased with sunitinib and increased with placebo). Decreases in sKIT levels were a significant predictor of longer time to tumor progression (TTP). Patients with reduced levels at the end of cycle 2 had a median TTP of 34.3 weeks versus 16.0 weeks for patients with increased levels [hazard ratio, 0.71; 95% confidence interval (95% CI), 0.61-0.83; P < 0.0001], and changes in sKIT levels replaced treatment as a stronger predictor of TTP (PTE, 0.80; 95% CI, 0.34-3.70), showing even greater surrogacy on cycle 3 day 1 (PTE, 0.98; 95% CI, 0.39-3.40).The results suggest that circulating plasma sKIT levels seem to function as a surrogate marker for TTP in gastrointestinal stromal tumor patients. Additional studies are warranted to confirm and expand these findings.
Effect of salbutamol and ipratropium bromide on airway calibre and bronchial reactivity in asthma and chronic bronchitis
Authors: B G Higgins, R M Powell, S Cooper, A E Tattersfield
Journal: European Respiratory Journal (1991)

Bronchial reactivity to agonists such as histamine is seen in both chronic bronchitis and asthma, two conditions with different pathological changes in the airways. Salbutamol, when given acutely, reduces bronchial reactivity in patients with asthma, but the mechanism has not been clarified. To determine whether the effect of salbutamol depends on the pathological changes underlying the increased reactivity, we have compared the effect of salbutamol and ipratropium on bronchial reactivity in nine patients with asthma and ten with chronic bronchitis. Each drug was given on separate days in increasing doses (5, 100, 750, 1,000 micrograms) according to a double-blind, randomized design. Changes in forced expiratory volume in one second (FEV1) and specific airways conductance (sGaw) were measured after each dose, and the provocative concentration of histamine causing a 20% fall in the FEV1 (PD20) was determined after the last dose. Salbutamol and ipratropium were equipotent in the asthmatic subjects and caused a similar maximal increase in FEV1 (0.58 and 0.57 l) and sGaw (0.166 and 0.154 s-1.kPa-1). The two drugs also produced similar changes in the patients with chronic bronchitis, although the maximum response to both drugs was smaller (FEV1 0.29 and 0.32 l; sGaw 0.056 and 0.060 s-1.kPa-1; p less than 0.05). Despite differences in bronchodilatation the increase in histamine PD20 following salbutamol was similar in the asthmatic and bronchitic subjects (2.26 and 1.90 doubling doses (DD)) and greater in both groups (p less than 0.05) than the change in PD20 with ipratropium (0.84 and 0.56 DD).(ABSTRACT TRUNCATED AT 250 WORDS)
MINER'S NYSTAGMUS
Authors: T. H. Butler
Journal: BMJ (1910)

3. The macular figure, as Mr. Gunn stated, is caused by tension lines centred at the fovea, the greatest stress being just beneath the intima.4. The phagocytes of the retina consist of several kinds, as follows: (1) Wander-cells;.(2) connective tissue cor- puscles; (3) epitheloid corpuscles of the nerve fibre layer; (4) epithelioid corpuscles of the outer granule layer-the two latter varieties being in close relation to the supporting fibres of Muller.
Foot Ulcer Risk Is Lower in South-Asian and African-Caribbean Compared With European Diabetic Patients in the U.K.
Authors: Caroline A. Abbott, Adam P. Garrow, Anne L. Carrington, Julie Morris, Ernest R. Van Ross, Andrew J. Boulton
Journal: Diabetes Care (2005)

OBJECTIVE—To determine 1) foot ulcer rates for European, South-Asian, and African-Caribbean diabetic patients in the U.K and 2) the contribution of neuropathy and peripheral arterial disease (PAD) differences to altered ulcer risk between the groups. RESEARCH DESIGN AND METHODS—In this U.K. population–based study, we screened 15,692 type 1 and type 2 diabetic patients in the community health care setting for foot ulcers, foot deformities, neuropathy, and PAD plus other characteristics. In total, 13,409 were European (85.5%), 1,866 were South Asian (11.9%), and 371 were African Caribbean (2.4%). RESULTS—The age-adjusted prevalence of diabetic foot ulcers (past or present) for Europeans, South Asians, and African Caribbeans was 5.5, 1.8, and 2.7%, respectively (P &amp;lt; 0.0001). Asians and African Caribbeans had less neuropathy, PAD, and foot deformities than Europeans (P = 0.003). The unadjusted risk of ulcer (odds ratio [OR]) for Asians versus Europeans was 0.29 (95% CI 0.20–0.41) (P &amp;lt; 0.0001). PAD, neuropathy, foot deformities, and insulin use attenuated the age-adjusted OR from 0.32 to 0.52 (0.35–0.76) (P &amp;lt; 0.0001). African-Caribbean versus European ulcer risk in males was attenuated from 0.60 to 0.71 by vibration sensation. CONCLUSIONS—South Asians with diabetes in the U.K. have about one-third the risk of foot ulcers of Europeans. The lower levels of PAD, neuropathy, insulin usage, and foot deformities of the Asians account for approximately half of this reduced foot ulcer risk. Lower neuropathy is the main contributor to the reduced African-Caribbean ulcer rate, particularly in men. The reasons for these ethnic differences warrant further investigation.
Effect of lipopolysaccharide stimulation on the transcription and translation of messenger RNA for cell surface immunoglobulin M.
Authors: D Yuan, P W Tucker
Journal: The Journal of Experimental Medicine (1982)

Analysis of mu-specific mRNA in the B cell tumor line, BCL1, shows that the cells contain predominantly mRNA for mu chain of membrane-bound immunoglobulin M (IgM) (2.7 kb, mu m mRNA). Stimulation of the cells to Ig secretion by lipopolysaccharide (LPS) results in a 6-12 fold increase in amount of mRNA for the mu chain of secreted IgM (2.4 kb mu s mRNA). The increase in mu s mRNA is accompanied by a 3-4-fold increase in mu m mRNA. The rate of mu chain synthesis of membrane IgM in LPS-stimulated cells is, however, reduced by at least twofold, suggesting that both transcriptional and translational regulatory events are involved in the induction of B lymphocytes to secretion.