tbuckley/cabot-search huggingface dataset:
Endoscopic Time-Lapse Imaging of Immune Cells in Infarcted Mouse Hearts
Authors: Keehoon Jung, Pilhan Kim, Florian Leuschner, Rostic Gorbatov, Jun Ki Kim, Takuya Ueno, Matthias Nahrendorf, Seok Hyun Yun
Journal: Circulation Research (2013)

High-resolution imaging of the heart in vivo is challenging owing to the difficulty in accessing the heart and the tissue motion caused by the heartbeat.Here, we describe a suction-assisted endoscope for visualizing fluorescently labeled cells and vessels in the beating heart tissue through a small incision made in the intercostal space.A suction tube with a diameter of 2 to 3 mm stabilizes the local tissue motion safely and effectively at a suction pressure of 50 mm Hg. Using a minimally invasive endoscope integrated into a confocal microscope, we performed fluorescence cellular imaging in both normal and diseased hearts in live mice for an hour per session repeatedly over a few weeks. Real-time imaging revealed the surprisingly rapid infiltration of CX3CR1(+) monocytes into the injured site within several minutes after acute myocardial infarction.The time-lapse analysis of flowing and rolling (patrolling) monocytes in the heart and the peripheral circulation provides evidence that the massively recruited monocytes come first from the vascular reservoir and later from the spleen. The imaging method requires minimal surgical preparation and can be implemented into standard intravital microscopes. Our results demonstrate the applicability of our imaging method for a wide range of cardiovascular research.
Pneumococcal Polysaccharide Vaccine Efficacy
Authors: J C Butler, R F Breiman, J F Campbell, H B Lipman, C V Broome, R R Facklam
Journal: JAMA (1993)

To determine pneumococcal polysaccharide vaccine efficacy in selected populations at risk for serious pneumococcal infection for whom vaccination is currently recommended and to assess duration of protection after vaccination.Vaccine efficacy was estimated using indirect cohort analysis to compare the proportion of pneumococcal infections caused by serotypes included in the vaccines of vaccinated and unvaccinated persons who were identified during 14 years of national surveillance.Hospital laboratories in the United States that submitted pneumococcal isolates to the Centers for Disease Control and Prevention between May 1978 and April 1992.A total of 2837 persons older than 5 years who had pneumococcus isolated from blood or cerebrospinal fluid.Overall efficacy for preventing infection caused by serotypes included in the vaccine was 57% (95% confidence interval [CI], 45% to 66%). Efficacy among persons with diabetes mellitus was 84% (95% CI, 50% to 95%); with coronary vascular disease, 73% (95% CI, 23% to 90%); with congestive heart failure, 69% (95% CI, 17% to 88%); with chronic pulmonary diseases, 65% (95% CI, 26% to 83%); and with anatomic asplenia, 77% (95% CI, 14% to 95%). Efficacy was not documented for patients with alcoholism or cirrhosis, sickle cell disease, chronic renal failure, lymphoma, leukemia, or multiple myeloma, although sample sizes were small for these groups. Efficacy for immunocompetent persons older than 65 years was 75% (95% CI, 57% to 85%). Efficacy did not decline with increasing interval after vaccination: 5 to 8 years after vaccination it was 71% (95% CI, 24% to 89%), and 9 years or more after vaccination it was 80% (95% CI, 16% to 95%).Intensified efforts to improve pneumococcal vaccine coverage among certain populations for whom vaccination is currently recommended is indicated, but universal revaccination is not warranted at this time.
Hydrogen peroxide-induced epithelial injury: the protective role of intracellular nonprotein thiols (NPSH)
Authors: B Mulier, I Rahman, T Watchorn, K Donaldson, W MacNee, PK Jeffery
Journal: European Respiratory Journal (1998)

Injury to the alveolar region is a hallmark of the adult respiratory distress syndrome (ARDS) whereas injury to the epithelium of the conducting airways is a characteristic of asthma. Reactive oxygen species have been implicated as mediators of lung injury in both of these conditions. We have investigated the relationship between intracellular nonprotein thiols (NPSH), and the release of the cytosolic enzyme lactate dehydrogenase (LDH), as an index of cell injury, following treatment of the human alveolar type II-like epithelial cell line (A549 cells) or the human bronchial epithelial cell line (16HBE140-) with hydrogen peroxide (H2O2). We have also assessed the protective effects of pre-incubation of both of these cells lines with H2O2 or enhancement of intracellular NPSH against H2O2-induced cell injury. Exposure of A549 and 16HBE140- cells to H2O2 (0.1 mM and 1 mM respectively for 16 h) produced the release of 40% of the total cellular LDH. H2O2 exposure produced an initial dose-dependent decrease in NPSH in A549 cells, with a subsequent increase to above control values. 16HBE140- cells also showed a dose-dependent decrease in NPSH following exposure to H2O2. Pretreatment of A549 cells with 0.1 mM H2O2 followed by subsequent exposure to H2O2 did not protect against H2O2-induced LDH release in this epithelial cell line. Pre-incubation with 2 mM N-acetylcysteine (NAC) increased NPSH but not intracellular reduced glutathione and resulted in total inhibition of H2O2-induced LDH release in both cell types. Pretreatment with reduced glutathione protected both cell types against the injurious effects of H2O2, whereas glutathione monethyl ester (GSHMEE) only partially protected A549 cells and had no effect in 16HBE140- cells. Intracellular cysteine levels were increased in both cell lines following NAC exposure but not sufficiently to account for the increase in NPSH levels. These observations raise the possibility that a critical concentration of nonprotein thiols may be necessary to protect pulmonary epithelial cells against hydrogen peroxide-induced injury.
Vascular endothelial growth factor receptor 1 expression in nasal polyp tissue
Authors: S. Bobic, V. Hox, I. Callebaut, S. Vinckier, B. Jonckx, J.-M. Stassen, M. Jorissen, P. Gevaert, P. Carmeliet, C. Bachert, J. L. Ceuppens, P. W. Hellings
Journal: Allergy (2013)

Background Edema represents a key feature of nasal polyp (NP) disease. Members of the vascular endothelial growth factor (VEGF) family may be involved, but the precise role of VEGF-A, VEGF-B, placental growth factor (PlGF), and their receptors VEGFR1 and VEGFR2 in NP edema formation remains elusive. Objective Exploring the expression of VEGF family members and their receptors and their correlation with clinical, radiological, and edema markers in NP. Methods The expression of VEGF-A, VEGF-B, PlGF, VEGFR1, and VEGFR2 was measured in NP (n = 23) and control tissue (n = 22) at mRNA and protein level. Edema was evaluated by measuring albumin levels and wet/dry ratios. Computed tomography (CT) scans were scored using the Lund-Mackay scoring system. IL-5 mRNA expression was determined by real-time RT-PCR. Cell suspensions from NP (n = 10) and control tissue (n = 12) were stimulated in vitro with IL-1β or TNFα. Results mRNA expression of VEGFR1 and VEGF-B was significantly higher in NP compared with control tissue. Expression levels of VEGF-B and VEGFR1 significantly correlated with NP albumin content (VEGF-B: P = 0.0208; VEGFR1: P = 0.0293), CT scan scores (VEGF-B: P = 0.0075; VEGFR1: P = 0.0068), and IL-5 mRNA (VEGF-B: P = 0.0027; VEGFR1: P = 0.0001). In vitro stimulation of control and NP tissue cell suspensions with IL-1β or TNFα significantly reduced the expression of VEGFR2 in control tissue, without altering VEGFR1 and VEGF-B expression. hVEGF-B induced nitric oxide production in NP macrophages (P < 0.05). Conclusion Expression levels of VEGFR1 and VEGF-B correlate with edema and clinical markers of NP disease and therefore represent potential therapeutic targets.
Surfactant protein D (SPD) and C-reactive protein (CRP) in patient with low respiratory tract infections (LRTI)
Authors: Tetyana Pertseva, Kateryna Gashynova, Olga Shtepa
Journal: European Respiratory Journal (2013)

The aim of study was to evaluate the diagnostic significance of plasma SPD and CRP in patients with LRTI.

Study population. 4 patients with COPD acute exacerbations (AE COPD), 8 patients with community acquired pneumonia (P) and 10 healthy persons (H) made the study sample.

Methods. Plasma CRP and SPD were measured in addition to physical examination, spirometry and chest X-Ray.

Results are shown in table 1.

View this table:



There was no any correlation between SPD and CRP either in patients with AE COPD, or in H (R = -0.4, p = 0.6; R = -0.47, p = 0.16 respectively). But SPD significantly correlate with CRP in patients with P (R = 0.8, p = 0.01).

Conclusions: 1) Both SPD and CRP increases in patients with LRTI.

2) Probably SPD more significantly reflects long-term lung inflammation, while CRP reflects acute injury.

3) Plasma SPD strongly positively correlates with CRP in patients with P.
Efficacy of topical treatments for cutaneous warts: a meta-analysis and pooled analysis of randomized controlled trials
Authors: C.S. Kwok, R. Holland, S. Gibbs
Journal: British Journal of Dermatology (2011)

Many topical treatments for cutaneous warts exist and previous reviews of trials did not follow intention-to-treat (ITT) principles for analysis. We aimed to perform a meta-analysis and pooled analysis of randomized controlled trials (RCTs) of topical treatment for cutaneous warts using ITT principles. Systematic electronic searches (Cochrane library, Medline, Embase, Clinical trial registers) were conducted in May 2009. Included trials reported completed cure of warts and data were extracted from these trials. We performed random-effects meta-analysis and assessed heterogeneity using the I(2) statistic and conducted a pooled analysis of each treatment. We found 77 relevant studies of which the majority were of low methodological quality. Salicylic acid (SA) was superior to placebo with a risk ratio (RR) for cure of 1·60 [95% confidence interval (CI) 1·15-2·24]. Cryotherapy was not statistically better than placebo, RR 0·89 (95% CI 0·27-2·92), but aggressive cryotherapy was significantly better than gentle cryotherapy with a RR of 2·06 (95% 1·20-3·52). Combined therapy of SA and cryotherapy had a higher cure rate than either SA or cryotherapy alone. The results of the pooled analysis found a cure rate of 23% (5-73%) in placebo trials, 52% (0-87%) in SA trials, 49% (0-69%) in cryotherapy trials, 54% (45-75%) in aggressive cryotherapy trials and 58% (38-78%) in the combined cryotherapy and SA trials. Aside from the use of SA and aggressive cryotherapy there is insufficient evidence from RCTs to support the use of other therapies. Higher quality evidence is needed to evaluate other therapies.
Metformin Use and All-Cause and Prostate Cancer–Specific Mortality Among Men With Diabetes
Authors: David Margel, David R. Urbach, Lorraine L. Lipscombe, Chaim M. Bell, Girish Kulkarni, Peter C. Austin, Neil Fleshner
Journal: Journal of Clinical Oncology (2013)

Purpose To evaluate the association between cumulative duration of metformin use after prostate cancer (PC) diagnosis and all-cause and PC-specific mortality among patients with diabetes. Patients and Methods We used a population-based retrospective cohort design. Data were obtained from several Ontario health care administrative databases. Within a cohort of men older than age 66 years with incident diabetes who subsequently developed PC, we examined the effect of duration of antidiabetic medication exposure after PC diagnosis on all-cause and PC-specific mortality. Crude and adjusted hazard ratios (HRs) were calculated by using a time-varying Cox proportional hazard model to estimate effects. Results The cohort consisted of 3,837 patients. Median age at diagnosis of PC was 75 years (interquartile range [IQR], 72 to 79 years). During a median follow-up of 4.64 years (IQR, 2.7 to 7.1 years), 1,343 (35%) died, and 291 patients (7.6%) died as a result of PC. Cumulative duration of metformin treatment after PC diagnosis was associated with a significant decreased risk of PC-specific and all-cause mortality in a dose-dependent fashion. Adjusted HR for PC-specific mortality was 0.76 (95% CI, 0.64 to 0.89) for each additional 6 months of metformin use. The association with all-cause mortality was also significant but declined over time from an HR of 0.76 in the first 6 months to 0.93 between 24 and 30 months. There was no relationship between cumulative use of other antidiabetic drugs and either outcome. Conclusion Increased cumulative duration of metformin exposure after PC diagnosis was associated with decreases in both all-cause and PC-specific mortality among diabetic men.
Procalcitonin, A Donor-Specific Predictor of Early Graft Failure-Related Mortality After Heart Transplantation
Authors: Frank D. Wagner, Britta Jonitz, Evgenij V. Potapov, Naser Qedra, Karl Wegscheider, Klaus Abraham, Ekaterina A. Ivanitskaia, Matthias Loebe, Roland Hetzer
Journal: Circulation (2001)

To date, donor-specific markers to predict outcome after heart transplantation (HTx) are unknown. Increased procalcitonin (PCT) levels have been found in infectious inflammation with systemic reactions and/or poor organ perfusion but have not been studied in heart donors. We evaluated PCT as a predictor of early graft failure-related mortality after HTx.PCT and C-reactive protein (CRP) serum concentrations were measured in samples collected immediately before pericardium opening from 81 consecutive brain-dead multiple-organ donors. Donors for high-urgency-status recipients (n=2) were excluded from analysis. The remaining donors were retrospectively divided into 2 groups: donors for recipients who died within 30 days after HTx, after an early graft failure (group II, n=8), and all other donors (group I, n=71). No differences in donor and recipient demographic characteristics were found between groups. Areas under the receiver operating characteristic curves for graft failure-related mortality were 0.71 for PCT and 0.64 for CRP. A PCT value >2 ng/mL as a predictor of graft failure-related mortality had a specificity of 95.8% and sensitivity of 50.0%. The odds ratio for graft failure-related mortality for recipients of hearts from donors with PCT levels >2 ng/mL was 22.7 (unadjusted, 95% CI 3.7 to 137.8, P=0.0007) and 43.8 (after adjustment for prespecified potential confounders, 95% CI 1.4 to 1361.0, P=0.031).A PCT level >2 ng/mL in a cardiac donor at the time of explantation appears to predict early graft failure-related mortality.
Intestinal myoelectric activity in response to live Vibrio cholerae and cholera enterotoxin.
Authors: J R Mathias, G M Carlson, A J DiMarino, G Bertiger, H E Morton, S Cohen
Journal: Journal of Clinical Investigation (1976)

The myoelectric response of the rabbit ileum was studied in response to live Vibrio cholerae culture, a whole cell lysate of cholera, and the purified enterotoxin. Each cholera preparation produced a series of highly organized migrating action potential complexes (MAPC). An MAPC was defined as action potential discharge with a duration of 2.5 s or longer, followed by similar activity on at least one other consecutive electrode site. The mean and modal onset time of MAPC activity occurred 4 h after the infection with live Vibrio cholerae culture, the freeze-dried whole cell lysate preparation, or the purified enterotoxin. After the onset of activity this pattern persisted for the duration of the recording period (up to 12 h). The MAPC had a mean propagation velocity of 0.85+/-0.07 cm/s (mean+/-SEM), which remained constant with time. Direct visual observation of the loop revealed that the MAPC's resulted in contractions that propelled intraluminal contents in an aborad direction. The mean fluid output from the 12-cm ileal loops was 6.4+/-1.1 ml/h (mean+/-SEM). Control experiments consisted of recordings from: (a) a ligated ileal loop into which nothing was placed; (b) a ligated ileal loop into which either uninfected culture broth or 0.9% NaCl solution was injected; (c) a ligated ileal loop infused with 0.9% NaCl solution at a rate of 11.2 ml/h, and (d) rapid injection of 1.0, 2.5, 5.0, or 10.0-ml boluses of 0.9% NaCl into the proximal catheter. MAPC activity was not observed in any of the control experiments. These studies indicate that in addition to a secretory component to cholera, there exists a highly organized MAPC that results in contractions that propel intraluminal contents in an aborad direction.
Role of leptin and melanocortin signaling in uremia-associated cachexia
Authors: Wai Cheung, Pin X. Yu, Brian M. Little, Roger D. Cone, Daniel L. Marks, Robert H. Mak
Journal: Journal of Clinical Investigation (2005)

The pathogenesis of cachexia in patients with uremia is unknown. We tested the hypothesis that uremia-associated cachexia is caused by leptin signaling through the hypothalamic melanocortin receptor 4 (MC4-R). We performed either subtotal nephrectomy (N) or sham operations in WT, leptin receptor–deficient (db/db), and MC4-R knockout (MC4-RKO) mice. The animals were on 17% protein diets, and none of the uremic animals were acidotic. WT-N mice produced a classic syndrome of cachexia characterized by decreased food intake, increased metabolic rate, and loss of lean body mass. Corrected leptin levels were elevated. db/db mice and MC4-RKO mice resisted the cachexic effects of uremia on weight gain, body composition, and metabolic rate. Likewise, treatment of WT mice with intracranial agouti-related peptide reversed the cachexic effects of uremia on appetite, weight gain, body composition, and metabolic rate. Gene expression of ubiquitin C and proteasome subunits C2, C3, and C9 was not changed in the uremic animals, suggesting that other pathways are involved in this model of nonacidotic uremic cachexia. The results of this study suggest that elevated circulating levels of cytokines such as leptin may be an important cause of uremia-associated cachexia via signaling through the central melanocortin system.
The Terminal Sequence of Complement Plays an Essential Role in Antibody-Mediated Renal Cell Apoptosis
Authors: TOSHINOBU SATO, MIENEKE G. A. VAN DIXHOORN, FRANS A. PRINS, ANDREW MOONEY, NICOLE VERHAGEN, YVONNE MUIZERT, JOHN SAVILL, LEENDERT A. VAN ES, MOHAMED R. DAHA
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Mesangial cell (MC) injury is a characteristic feature in the early phase of Thy.1 nephritis. The present study investigates the contribution of complement to MC apoptosis in this experimental model of kidney disease in rats. Thy.1 nephritis was induced by injection of mouse anti-Thy.1 monoclonal antibody (ER4G). To assess the contribution of the terminal sequence of complement on apoptosis, the studies were performed in complement-sufficient PVG/c (PVG/c+) rats and in rats deficient in complement C6 (PVG/c-). Apoptosis was monitored by assessment of the number of condensed nuclei in kidney sections stained with periodic acid-Schiff (PAS) and by the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method and expressed as number of apoptotic cells per 50 glomerular cross sections. In the PAS method, 1 h after intravenous injection of ER4G, PVG/c+ rats exhibited 160.9 ± 49.5 apoptotic cells, whereas PVG/c- rats had only 3.2 ± 1.4 apoptotic cells. Control rats exhibited 0.9 ± 0.6 apoptotic cells. These findings were confirmed with the TUNEL method. In PVG/c- rats, a maximum number of 8.8 ± 3.1 TUNEL-positive (TUNEL + ) cells was found at 6 h followed by a decline thereafter. In PVG/c+ rats, apoptosis was associated with deposition of C6 and C5b-9. Restoration of the complement system of PVG/c- rats with purified human C6 resulted in an increase of apoptosis at 1 h after injection of ER4G from minimal numbers to 239.9 ± 52.4 TUNEL + cells. These studies appear to indicate for the first time that the terminal sequence of complement is involved in induction of apoptosis.
Screening for prostate cancer in the UK
Authors: J. L Donovan, S. J Frankel, D. E Neal, F. C Hamdy
Journal: BMJ (2001)

Screening for prostate cancer is controversial. Findings from systematic and other reviews consistently conclude that there is insufficient evidence to recommend its introduction because of concerns that it may not improve survival or quality of life and may thus cause more harm than good.1–3 Current government policy in the United Kingdom, expressed in the NHS prostate cancer programme, confirms this view, but adds that “any man considering a PSA [prostate specific antigen] test will be given detailed information to enable him to make an informed choice about whether to proceed with a test or not.”4 This implies that asymptomatic men may have the test if they want, so there is now ambiguity about whether screening is supported and confusion about what this policy means in practice.

The assumption may be that most men will not want to be tested once they are informed of the uncertainties. In the United States several studies have shown that informed choice can reduce prostate specific antigen testing in some groups by up to one half.5–7 But this may not apply in the United Kingdom. A systematic review of the use of decision aids has …
Cytokine mRNA expression during an in vitro response of human B lymphocytes: kinetics of B cell tumor necrosis factor alpha, interleukin (IL)6, IL-10, and transforming growth factor beta 1 mRNAs.
Authors: T Matthes, C Werner-Favre, H Tang, X Zhang, V Kindler, R H Zubler
Journal: The Journal of Experimental Medicine (1993)

Expression of mRNA for eight cytokines was analyzed in an in vitro response-proliferation and Ig-secretion--of normal human B lymphocytes. This was made possible by the use of murine thymoma cells as helper cells in conjunction with human T cell supernatant, and the design of human DNA sequence-specific primers for RT-polymerase chain reaction. mRNAs for interleukin (IL)2 and IL-4, but also for IL-1 alpha and IL-1 beta remained undetectable during the whole culture period in highly purified B cells prepared by a three-step purification protocol. However, tumor necrosis factor alpha and IL-6 mRNAs peaked during days 1-3 after culture start and became undetectable after 5-6 d, shortly before bulk B cell proliferation started to decline. In contrast, transforming growth factor beta 1 mRNA, after a progressive increase during the first few days, and IL-10 mRNA, after a peak on days 1-3, remained detectable in immunoglobulin (Ig)-secreting cultures throughout the observation period of 22 d. Clonal analysis on 8-d cultures that had been seeded with single B cells by autocloning with the cell sorter, revealed that 85% of 77 B cell clones studied, expressed TGF-beta 1 mRNA, and only 19% IL-10 mRNA. These findings show a differentiation stage-related cytokine program during a B cell response, whereby (a) B cells can become activated without IL-1 alpha or IL-1 beta expression; (b) mRNA for positive (IL-10) and negative (TGF-beta 1) autoregulatory factors coexists in cell populations during the later phase of the response, although not necessarily in all B cell clones; and (c) normal Ig-secreting cells cease IL-6 expression in contrast to their malignant counterparts, myeloma cells.
The Effects of a Variety of Hemodynamic Changes on the Rapid and Slow Components of the Circulation in the Human Forearm1
Authors: Edward D. Freis, Harold W. Schnaper
Journal: Journal of Clinical Investigation (1958)

Freis conducted many studies of circulation processes concurrently with his clinical investigation, to better understand the
   actions of antihypertensive drugs. In this article he and Schnaper report on experiments on the forearm circulation.