tbuckley/cabot-search huggingface dataset:
Processing of the laminin-332 α chain: from bedside to bench
Authors: C. Has
Journal: British Journal of Dermatology (2014)

Journal Article Processing of the laminin‐332 α chain: from bedside to bench Get access C. Has C. Has Department of Dermatology Medical Center – University of Freiburg Hauptstraße 7 79104 Freiburg Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 170, Issue 5, 1 May 2014, Pages 1008–1009, https://doi.org/10.1111/bjd.12956 Published: 01 May 2014
Preconditioning decreases Bax expression, PMN accumulation and apoptosis in reperfused rat heart
Authors: M Nakamura
Journal: Cardiovascular Research (2000)

Objective: Recent studies suggest that ischemic preconditioning (IPC) inhibits myocardial apoptosis after ischemia and reperfusion. This study tested the hypothesis that IPC reduces ischemia/reperfusion-induced myocardial apoptosis by inhibiting neutrophil (PMN) accumulation and altering expression of Bcl-2 and Bax proteins. Methods: Eighteen rats were subjected to 30 min of left coronary artery occlusion followed by 180 min of reperfusion with IPC (5 min ischemia and 10 min of reperfusion, n=10) or without IPC (n=8). Myocardial apoptosis was detected histologically using the terminal transferase UTP nick end labeling (TUNEL) assay and confirmed by DNA ladder on agarose gel electrophoresis. PMN accumulation was detected immunohistochemically with anti-rat CD18 antibody (WT3) and expression of Bcl-2 and Bax proteins was analyzed using Western blot assay. Results: IPC significantly decreased TUNEL positive cells (% total nuclei) in the ischemic zone from 28.6±2.8 to 3.4± 0.9 (P<0.05), consistent with the absence of DNA ladders in the IPC group. IPC significantly attenuated PMN accumulation (cells/mm2 myocardium) in the ischemic zone from 243±19 to 118±19 (P<0.05). By regression analysis, there was a significant correlation between TUNEL positive cells and accumulated CD18 positive PMNs in the ischemic zone (r=0.8, P<0.001), which was shifted downward by IPC. Densitometrically, IPC significantly attenuated the ischemia/reperfusion-upregulated expression of Bax protein in the ischemic zone from 204±57% in the control group to 76±7% (P<0.05), while the expression of Bcl-2 was not different from the non-ischemic zone in either group. Conclusion: These data suggest that ischemic preconditioning may reduce myocardial apoptosis by inhibiting PMN accumulation and down-regulating expression of Bax.
Longitudinal lung function in idiopathic NSIP: what are we missing?
Authors: H. Chen, A. Gomez, A. Shum, H. R. Collard
Journal: European Respiratory Journal (2009)

To the Editors: 

In a recent article, Park et al. 1 described the clinical course and changes in lung function of 83 patients classified as idiopathic nonspecific interstitial pneumonia (NSIP). Park et al. 1 found that 81% of patients with fibrotic NSIP had improved or stable lung function over time after initial treatment. Specifically, the authors showed an increase in the percentage of patients with an improvement in forced vital capacity and diffusing capacity of the lung for carbon monoxide over time, as well as an increase in the magnitude of change in observed lung function. However, …
Prediction of MLH1 and MSH2 Mutations in Lynch Syndrome
Authors: Judith Balmaña, David H. Stockwell, Ewout W. Steyerberg, Elena M. Stoffel, Amie M. Deffenbaugh, Julia E. Reid, Brian Ward, Thomas Scholl, Brant Hendrickson, John Tazelaar, Lynn Anne Burbidge, Sapna Syngal
Journal: JAMA (2006)

ContextLynch syndrome is caused primarily by mutations in the mismatch repair genes MLH1 and MSH2.ObjectivesTo analyze MLH1/MSH2 mutation prevalence in a large cohort of patients undergoing genetic testing and to develop a clinical model to predict the likelihood of finding a mutation in at-risk patients.Design, Setting, and ParticipantsPersonal and family history were obtained for 1914 unrelated probands who submitted blood samples starting in the year 2000 for full gene sequencing of MLH1/MSH2. Genetic analysis was performed using a combination of sequence analysis and Southern blotting. A multivariable model was developed using logistic regression in an initial cohort of 898 individuals and subsequently prospectively validated in 1016 patients. The complex model that we have named PREMM1,2 (Prediction of Mutations in MLH1 and MSH2) was developed into a Web-based tool that incorporates personal and family history of cancer and adenomas.Main Outcome MeasureDeleterious mutations in MLH1/MSH2 genes.ResultsOverall, 14.5% of the probands (130/898) carried a pathogenic mutation (MLH1, 6.5%; MSH2, 8.0%) in the development cohort and 15.3% (155/1016) in the validation cohort, with 42 (27%) of the latter being large rearrangements. Strong predictors of mutations included proband characteristics (presence of colorectal cancer, especially ≥2 separate diagnoses, or endometrial cancer) and family history (especially the number of first-degree relatives with colorectal or endometrial cancer). Age at diagnosis was particularly important for colorectal cancer. The multivariable model discriminated well at external validation, with an area under the receiver operating characteristic curve of 0.80 (95% confidence interval, 0.76-0.84).ConclusionsPersonal and family history characteristics can accurately predict the outcome of genetic testing in a large population at risk of Lynch syndrome. The PREMM1,2 model provides clinicians with an objective, easy-to-use tool to estimate the likelihood of finding mutations in the MLH1/MSH2 genes and may guide the strategy for molecular evaluation.
Human epidermal growth factor for the stratification of synovial lining layer and neovascularisation in rheumatoid arthritis.
Authors: S Shiozawa, K Shiozawa, Y Tanaka, I Morimoto, M Uchihashi, T Fujita, K Hirohata, Y Hirata, S Imura
Journal: Annals of the Rheumatic Diseases (1989)

Immunohistochemical study showed selective localisation of human epidermal growth factor (hEGF) to the synovial lining layer. Although the synovial lining layer of the rheumatoid, osteoarthritic, and traumatic joints was hEGF positive, hEGF staining was especially dense at the rheumatoid synovial lining layer; the staining increasing linearly according to the degree of stratification of the lining layer (r = 1). Human epidermal growth factor was ultrastructurally localised to cytoplasm, especially to rough endoplasmic reticulum, of the synovial lining fibroblast-like (type B) cell. Only the cell surface of macrophage-like (type A) cells was hEGF positive. When different histological variables were compared with each other a positive correlation was found between hEGF staining of the synovial lining layer and the degree of neovascularisation of rheumatoid synovium (r = 0.72). Although some lymphocytes were weakly hEGF positive, neovascularisation did not correlate with the extent of lymphocyte infiltration or of hEGF staining of lymphocytes. Lymphocyte infiltration or hEGF staining of lymphocytes did not correlate with hEGF staining of the synovial lining layer, whereas the lymphocyte infiltration correlated positively with the extent of perivascular accumulation of lymphocytes (r = 0.89). These findings suggest that (a) hEGF is synthesised by and secreted through endoplasmic reticulum and Golgi apparatus from the synovial lining type B cell; (b) hEGF is at least partially responsible for the pathogenesis of stratification of the rheumatoid synovial lining layer, and perhaps of neovascularisation of the rheumatoid synovium, whereas it is not responsible for lymphocyte accumulation to the rheumatoid synovium.
Dendritic cell-based vaccination combined with gemcitabine increases survival in a murine pancreatic carcinoma model
Authors: C Bauer, F Bauernfeind, A Sterzik, M Orban, M Schnurr, H A Lehr, S Endres, A Eigler, M Dauer
Journal: Gut (2007)

<b>Background:</b> Tumour-specific cytotoxic T lymphocytes (CTLs) can be activated in vivo by vaccination with dendritic cells (DCs). However, clinical responses to DC-based vaccination have only been observed in a minority of patients with solid cancer. Combination with other treatment modalities such as chemotherapy may overcome immunoresistance of cancer cells. It has been shown previously that gemcitabine sensitises human pancreatic carcinoma cells against CTL-mediated lysis. Here, a murine pancreatic carcinoma model was used to investigate whether combination with gemcitabine increases therapeutic efficacy of DC-based vaccination. <b>Methods:</b> Bone marrow-derived DCs from C57BL/6 mice were loaded with UV-irradiated, syngeneic Panc02 carcinoma cells and were administered subcutaneously. For prophylactic vaccination, mice were vaccinated three times at weekly intervals prior to tumour challenge with Panc02 cells. Therapeutic vaccination was started when tumours formed a palpable nodule. Gemcitabine was administered intraperitoneally twice weekly. <b>Results:</b> Prophylactic DC-based vaccination completely prevented subcutaneous and orthotopic tumour development and induced immunological memory as well as tumour antigen-specific CTLs. In the subcutaneous tumour model, therapeutic DC-based vaccination was equally effective as gemcitabine (14% vs 17% survival at day 58 after tumour challenge; controls, 0%). Combination of the two strategies significantly increased survival of tumour-bearing mice (50% at day 58 after tumour challenge). DC-based vaccination also prevented death from pulmonary metastatisation after intravenous injection of Panc02 cells. <b>Conclusion:</b> DC-based immunotherapy may not only be successfully combined with gemcitabine for the treatment of advanced pancreatic carcinoma, but may also be effective in preventing local recurrence or metastatisation in tumour-free patients.
PFI scheme changes are inadequate, MPs say
Authors: A. O'Dowd
Journal: BMJ (2012)

Government plans to improve private finance initiative (PFI) schemes that help fund new hospitals are too weak and fail to deal with the danger of wasting public money, MPs have concluded.

MPs on the House of Commons Treasury Committee have published the government’s response to their report of last year on PFI funding and say that progress has been made but basic problems with the scheme remain.

Under PFI projects, private companies build hospitals, and NHS trusts repay them typically over 30 years.

The scheme was criticised in the select committee’s report published in August last year (www.publications.parliament.uk/pa/cm201012/cmselect/cmtreasy/1146/114602.htm) for being a highly inefficient way of financing projects and not providing taxpayers with good value for …
Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: a randomised, double-blind, placebo-controlled trial
Authors: George E Armah, Samba O Sow, Robert F Breiman, Michael J Dallas, Milagritos D Tapia, Daniel R Feikin, Fred N Binka, A Duncan Steele, Kayla F Laserson, Nana A Ansah, Myron M Levine, Kristen Lewis, Michele L Coia, Margaret Attah-Poku, Joel Ojwando, Stephen B Rivers, John C Victor, Geoffrey Nyambane, Abraham Hodgson, Florian Schödel, Max Ciarlet, Kathleen M Neuzil
Journal: The Lancet (2010)
Teaching senior oncologists communication skills: results from phase I of a comprehensive longitudinal program in the United Kingdom.
Authors: L Fallowfield, M Lipkin, A Hall
Journal: Journal of Clinical Oncology (1998)

PURPOSE To determine the communication difficulties experienced by clinicians in cancer medicine and to develop, implement, and evaluate communication skills training courses. METHODS One hundred seventy-eight senior clinicians attended 1 1/2- or 3-day residential courses designed to enhance skills development, knowledge acquisition, and personal awareness. Course content included structured feedback, video review of interviews, interactive group demonstrations, and discussion in groups of four led by trained facilitators. The main outcomes were self-rated confidence in key aspects of communication, attitudinal shift toward more patient-centered interviewing, perceived changes in personal practice, and initiation of teaching programs for junior staff. RESULTS Less than 35% of the participants had received any previous communications training. Time, experience, and seniority had not improved skills; before the course, oncologists expressed difficulty with 998 different communication issues. Primary problems concerned giving complex information, obtaining informed consent, and handling ethnic and cultural differences. Confidence ratings for key communication areas were significantly improved postcourse (P &lt; .01). Three months postcourse, 95% of the physicians reported significant changes in their practice of medicine. Seventy-five percent had started new teaching initiatives in communication for junior clinicians. Clinicians showed positive shifts in attitude toward patients' psychosocial needs (P=.0002) and were more patient centered (P=.03). The courses were highly rated and 97% would "definitely" recommend them to colleagues. CONCLUSION Oncologists are hampered by inadequate communication skills training and will give up time to correct this. Subjective improvements reported immediately postcourse were maintained at 3 months. Resources for educational initiatives are needed to help both patients and their physicians.
Impact of Hyperthyroidism and Its Correction on Vascular Reactivity in Humans
Authors: Raffaele Napoli, Bernadette Biondi, Vincenzo Guardasole, Margherita Matarazzo, Francesco Pardo, Valentina Angelini, Serafino Fazio, Luigi Saccà
Journal: Circulation (2001)

Background — Although thyroid hormone (TH) exerts relevant effects on the cardiovascular system, it is unknown whether TH also regulates vascular reactivity in humans. Methods and Results — We studied 8 patients with hyperthyroidism, basally (H) and 6 months after euthyroidism was restored by methimazole (EU). Thirteen healthy subjects served as control subjects (C). We measured forearm blood flow (FBF) by strain-gauge plethysmography during intrabrachial graded infusion of acetylcholine, sodium nitroprusside (SNP), norepinephrine, and L-NMMA (inhibitor of NO synthesis). Basal FBF (in mL · dL −1 · min −1 ) was markedly higher in H than in C (5.8±1.2 and 1.9±0.1, respectively; P &lt;0.001) and was close to normal in EU (2.6±0.3, P &lt;0.01 versus H). During acetylcholine infusion, FBF increased much more in H (+33±5) than in C (+14±3, P &lt;0.01 versus H) and in EU (+20±5, P =0.01 versus H and P =NS versus C). In contrast, the response to SNP infusion was comparable in the patients and control subjects. During norepinephrine infusion, the fall in FBF was much more pronounced in H (−6±1) than in C (−0.7±0.3, P &lt;0.005 versus H) and in EU (−1.5±0.3, P &lt;0.01 versus H). Finally, inhibition of NO synthesis by L-NMMA decreased FBF by 2.8±0.6, 0.61±0.7, and 1.4±0.3 in H, C, and EU, respectively (H versus C and EU, P &lt;0.05). Conclusions — In hyperthyroidism, (1) the marked basal vasodilation is largely accounted for by excessive endothelial NO production, (2) vascular reactivity is exaggerated because of enhanced sensitivity of the endothelial component, (3) the vasoconstrictory response to norepinephrine is potentiated, and (4) this abnormal vascular profile is corrected when euthyroidism is restored by medical therapy. The data demonstrate that vascular endothelium is a specific target of TH.
Transfusion for variceal bleeding in cirrhotic patients.
Authors: P Hochain, V Merle, S Tuil, P Michel, P Ducrotte, E Lerebours, R Colin, T Dao
Journal: Gut (1996)

Letters the decreased CDAI scores, which are considered universally as unreliable and subjective assessments, remission induced in these patients by the novel treatment is probably only short lived.The high concen- trations of soluble TNF receptors show, in our opinion, that these patients have not achieved a stable remission.We have found that the concentration of the soluble TNF receptors in the urine is a useful prognostic indicator for determining the efficacy of treat- ment and predicting a change in the status of the disease: relapse and remission.
Moxifloxacin versus Ethambutol in the First 2 Months of Treatment for Pulmonary Tuberculosis
Authors: William J. Burman, Stefan Goldberg, John L. Johnson, Grace Muzanye, Melissa Engle, Ann W. Mosher, Shurjeel Choudhri, Charles L. Daley, Sonal S. Munsiff, Zhen Zhao, Andrew Vernon, Richard E. Chaisson
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Moxifloxacin has promising preclinical activity against Mycobacterium tuberculosis, but has not been evaluated in multidrug treatment of tuberculosis in humans.To compare the impact of moxifloxacin versus ethambutol, both in combination with isoniazid, rifampin, and pyrazinamide, on sputum culture conversion at 2 mo as a measure of the potential sterilizing activity of alternate induction regimens.Adults with smear-positive pulmonary tuberculosis were randomized in a factorial design to receive moxifloxacin (400 mg) versus ethambutol given 5 d/wk versus 3 d/wk (after 2 wk of daily therapy). All doses were directly observed.The primary endpoint was sputum culture status at 2 mo of treatment.Of 336 patients enrolled, 277 (82%) were eligible for the efficacy analysis, 186 (67%) were male, 175 (63%) were enrolled at African sites, 206 (74%) had cavitation on chest radiograph, and 60 (22%) had HIV infection. Two-month cultures were negative in 71% of patients (99 of 139) treated with moxifloxacin versus 71% (98 of 138) treated with ethambutol (p = 0.97). Patients receiving moxifloxacin, however, more often had negative cultures after 4 wk of treatment. Patients treated with moxifloxacin more often reported nausea (22 vs. 9%, p = 0.002), but similar proportions completed study treatment (88 vs. 89%). Dosing frequency had little effect on 2-mo culture status or tolerability of therapy.The addition of moxifloxacin to isoniazid, rifampin, and pyrazinamide did not affect 2-mo sputum culture status but did show increased activity at earlier time points.
P237 Comparison of COPD exacerbations with once-daily QVA149 versus twice-daily salmeterol/fluticasone combination: the ILLUMINATE study
Authors: C Vogelmeier, ED Bateman, H Chen, D Banerji
Journal: Thorax (2013)

<h3>Introduction</h3> Exacerbations are the most frequent cause of hospitalisation and death among patients with COPD. Combinations of long-acting bronchodilators maximise bronchodilation and may reduce the risk of exacerbations. QVA149, a once-daily dual bronchodilator containing the long-acting β<sub>2 </sub> agonist (LABA) indacaterol and long-acting muscarinic antagonist (LAMA) glycopyrronium, improves lung function, breathlessness and rescue medication use compared with twice-daily salmeterol/fluticasone combination (SFC), in patients with moderate-to-severe COPD.<sup>1</sup> <h3>Methods</h3> In this 26-week, multicenter, double-blind study, patients ≥ 40 years with COPD (forced expiratory volume in 1 second [FEV<sub>1</sub>] ≥40% to &lt;80% predicted and no history of exacerbations in the previous year) were randomised (1:1) to QVA149 110/50 µg or SFC 50/500 µg. In this post hoc analysis, we report the rate of mild, moderate or severe COPD exacerbations during 26 weeks of treatment with QVA149 or SFC. <h3>Results</h3> Of 522 patients randomised [QVA149 (n = 258), SFC (n = 264); mean age: 63.3 years; mean post-bronchodilator FEV<sub>1</sub>: 60.2% predicted], 82.6% completed. Rate ratio of QVA149 versus SFC [RR] of moderate or severe exacerbations was 0.80 (95% confidence interval [CI]: 0.41–1.56) and for all COPD exacerbations (mild, moderate, and severe), RR was 0.69 (95% CI: 0.44–1.07) (neither statistically significant). <h3>Conclusion</h3> Risk of exacerbations with once-daily QVA149 was numerically, but not statistically significantly, lower than twice-daily SFC in patients with moderate-to-severe COPD and no previous history of exacerbations. The LABA/LAMA combination QVA149 has the potential to be an alternative to LABA/ICS in preventing COPD exacerbations. <h3>Reference</h3> Vogelmeier <i>et al</i>. Lancet Respir Med 2013;1(1):50–60.
Accelerated thrombolysis and reperfusion in a canine model of myocardial infarction by liposomal encapsulation of streptokinase.
Authors: P D Nguyen, E A O'Rear, A E Johnson, E Patterson, T L Whitsett, R Bhakta
Journal: Circulation Research (1990)

The aim of thrombolytic therapy for acute myocardial infarction with plasminogen activators such as streptokinase is to lyse the coronary thrombus and reestablish blood flow as quickly as possible so that heart tissue loss is minimized and mortality rates are improved. Streptokinase has been encapsulated in large unilamellar phospholipid vesicles and tested in an animal model of acute myocardial infarction. The time required to restore vessel patency has been reduced more than 50% when compared with findings for free streptokinase. The total dosage of streptokinase required was lower, and smaller remnant thrombi were observed with the encapsulated agent. Results from this initial unoptimized study may have significant implications for further reduction in mortality from heart attacks by therapy with plasminogen activators.
Effects of the Japanese herbal medicine ?Sho-Saiko-To? (TJ-9) onin vitro interleukin-10 production by peripheral blood mononuclear cells of patients with chronic hepatitis C
Authors: M Yamashiki, A Nishimura, H Suzuki, S Sakaguchi, Y Kosaka
Journal: Hepatology (1997)

"Sho-saiko-to" (TJ-9) consists of 7 herbal components. In Japan, it is widely prescribed to patients with chronic viral liver disease. TJ-9 is known to suppress liver cancer development and possess macrobiotic effects, but its mode of action is not fully understood. This study investigated the following: 1) cytokine production levels, mainly interleukin (IL)-10, in peripheral blood mononuclear cells of chronic active hepatitis B and C patients, and healthy volunteers; 2) effects of TJ-9 on these productions; and 3) effects of each of its herb components on cytokine production in cell fractions. Results showed that without stimulants, IL-10 production in mononuclear cells of hepatitis B and C patients was significantly lower than that of healthy subjects (P < .01). IL-10 production induced by either phytohemagglutinin (PHA) or pokeweed mitogen (PWM) in mononuclear cells of hepatitis C patients were significantly lower than in patients with hepatitis B (P < .01) and healthy subjects (P < .05). IL-10 production induced by anti-CD3 or lipopolysaccharide (LPS) was significantly lower than in healthy subjects (P < .05). The addition of TJ-9 to the cultures strongly induced IL-10, and this induction was mainly attributable to the effects of 2 components (scutellaria root and glycyrrhiza root) on the monocyte/macrophage fraction. The production of IL-4 and IL-5 in cultures with concanavalin A (conA) was significantly higher in patients with hepatitis C than in the healthy subjects (P < .01; P < .05), but the addition of TJ-9 suppressed these increases by 25% to 33% (P < .01). Therefore, TJ-9 could adjust the decreased IL-10 production and the increased IL-4 and IL-5 production of mononuclear cells from patients with hepatitis C. Moderate regulation of the cytokine production system in patients with hepatitis C by using TJ-9 may be useful in the prevention of disease progression.
Parents discover their stillborn babies are alive four months after birth
Authors: I. Vlad
Journal: BMJ (2004)

Two babies born alive were declared dead at the Ploiesti maternity hospital in Prahova county, Romania. Almost four months after the parents were informed that their babies had died, the local authorities asked them to go back to the maternity hospital and take home their “abandoned” children.

This situation comes as a result of a practice dating back to the communist period, when it was common not to register babies who weighed less than 1000 g during the first 10 days of life, in order to have …