tbuckley/cabot-search huggingface dataset:
Androgen Receptor Coactivators Lysine-Specific Histone Demethylase 1 and Four and a Half LIM Domain Protein 2 Predict Risk of Prostate Cancer Recurrence
Authors: Philip Kahl, Lucia Gullotti, Lukas Carl Heukamp, Susanne Wolf, Nicolaus Friedrichs, Roland Vorreuther, Gerold Solleder, Patrick J. Bastian, Jörg Ellinger, Eric Metzger, Roland Schüle, Reinhard Buettner
Journal: Cancer Research (2006)

Prostate cancer biology varies from locally confined tumors with low risk for relapse to tumors with high risk for progression even after radical prostatectomy. Currently, there are no reliable biomarkers to predict tumor relapse and poor clinical outcome. In this study, we correlated expression patterns of the androgen receptor (AR) coactivators lysine-specific histone demethylase 1 (LSD1) and four and a half LIM-domain protein 2 (FHL2), AR, Gleason score, Gleason grade, and p53 expression in clinically organ confined prostate cancers with relapse after radical prostatectomy. Our data reveal that high levels of LSD1, nuclear expression of the FHL2 coactivator, high Gleason score and grade, and very strong staining of nuclear p53 correlate significantly with relapse during follow-up. No correlation exists with relapse and the expression of AR and cytoplasmic expression of FHL2. To confirm these data, we did quantitative reverse transcription-PCR and Western blot analyses in a subset of tumor specimens. Consistently, both LSD1 mRNA and protein levels were significantly up-regulated in high-risk tumors. We previously identified LSD1 and FHL2 as nuclear cofactors interacting specifically with the AR in prostate cells and showed that both stimulate androgen-dependent gene transcription. Our present study suggests that LSD1 and nuclear FHL2 may serve as novel biomarkers predictive for prostate cancer with aggressive biology and point to a role of LSD1 and FHL2 in constitutive activation of AR-mediated growth signals.
Comparison of phenotypes of polycystic kidney disease types 1 and 2
Authors: Nick Hateboer, Marjan A v Dijk, Nadja Bogdanova, Eliecer Coto, Anand K Saggar-Malik, Jose L San Millan, Roser Torra, Martijn Breuning, David Ravine
Journal: The Lancet (1999)
The Relationship between Normal Lung Sounds, Age, and Gender
Authors: VOLKER GROSS, ANKE DITTMAR, THOMAS PENZEL, FRANK SCHÜTTLER, PETER von WICHERT
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Auscultation is one of the most important noninvasive and feasible methods for the detection of lung diseases. Systematic changes in breathing sounds with increasing age are of diagnostic importance. To investigate these changes, we recorded lung sounds taken from four locations in the posterior thorax of 162 subjects, together with airflow. The data were analyzed according to age, sex, and smoking habit. In order to describe the power spectrum of the lung sounds, we calculated mean and median frequency, frequency with the highest power, and a ratio (Q) of relative power of the two frequency bands of 330 to 600 Hz and 60 to 330 Hz. Linear regression analysis was used as a measurement of age-dependence of these variables. Significant differences in Q were found in men versus women (p < 0.05), but not in smokers versus nonsmokers. Within the groups, a small but significant correlation existed between Q and age (r2 ⩽ 0.1, p < 0.05). For both men and women, a slight increase of the relative power in the frequency band of 330 to 600 Hz was recorded with increasing age. However, on the basis of large individual variations, these small changes ( Δ Q ∼ 5%, SD(Q) ⩾ ± 5%) have no clinical significance and need not to be considered in the automatic detection of lung diseases by analyzing lung sounds.
Convergence of physical and chemical signaling in the modulation of vascular smooth muscle cell cycle and proliferation by fibrillar collagen-regulated P66Shc
Authors: Yi-Ting Yeh, Chih-I Lee, Seh Hong Lim, Li-Jing Chen, Wei-Li Wang, Yung-Jen Chuang, Jeng-Jiann Chiu
Journal: Biomaterials (2012)
Motexafin Lutetium-Photodynamic Therapy of Prostate Cancer: Short- and Long-Term Effects on Prostate-Specific Antigen
Authors: Hiral Patel, Rosemarie Mick, Jarod Finlay, Timothy C. Zhu, Elizabeth Rickter, Keith A. Cengel, S. Bruce Malkowicz, Stephen M. Hahn, Theresa M. Busch
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The time course of serum prostate-specific antigen (PSA) response to photodynamic therapy (PDT) of prostate cancer was measured. Experimental Design: Seventeen patients were treated in a phase I trial of motexafin lutetium-PDT. PDT dose was calculated in each patient as the product of the ex vivo measured pre-PDT photosensitizer level and the in situ measured light dose. Serum PSA level was measured within 2 months before PDT (baseline), and at day 1; weeks 1 to 3; months 1, 2, and 3; months 4 to 6; and months 7 to 11 after PDT. Results: At 24 hours after PDT, serum PSA increased by 98% ± 36% (mean ± SE) relative to baseline levels (P = 0.007). When patients were dichotomized based on median PDT dose, those who received high PDT dose showed a 119% ± 52% increase in PSA compared with a 54% ± 27% increase in patients treated at low PDT dose. Patients treated with high versus low PDT dose showed a median biochemical delay of 82 versus 43 days (P = 0.024), with biochemical delay defined as the length of time between PDT and a nonreversible increase in PSA to a value greater than or equal to baseline. Conclusions: Results show PDT to induce large, transient increases in serum PSA levels. Patients who experienced high PDT dose showed greater short-term increase in PSA and a significantly more durable PSA response (biochemical delay). These data strongly promote the need for individualized delivery of PDT dose and assessment of treatment effect in PDT of prostate cancer. Information gained from such patient-specific measurements could facilitate the introduction of multiple PDT sessions in patients who would benefit.
Proliferation in human gastrointestinal epithelium using bromodeoxyuridine in vivo: data for different sites, proximity to a tumour, and polyposis coli.
Authors: C S Potten, M Kellett, D A Rew, S A Roberts
Journal: Gut (1992)

The distribution of DNA synthesising cells in the crypts of the epithelium in human small and large bowel after injection of bromodeoxyuridine into patients has been studied in relation to the position of the cells in the crypt using immunohistochemistry. Different sites of normal epithelium have been studied. The ileum has a shorter crypt and a very significantly smaller total cell population size. However, it has similar peak labelling index (LI) values to the colon, while the rectum has a lower peak LI value. The mean position of the label occurs at the 17th cell position in the ileum and at about the 22nd position in both the colon and rectum. The overall mean LI is significantly higher in the ileum at 17.8%, intermediate in the colon at 10.3%, and lowest in the rectum at 8.5%. There is thus an inverse relation between the likelihood of developing a tumour and the rate of cell proliferation as measured by the LI. Assuming a value of 8.6 hours for the duration of S, the data suggest that the cell cycle time in the mid crypt region is about 30 hours for the ileum and colon and about 37 hours for the rectum. Samples taken adjacent (within 1 cm) to a tumour show a general dampening of proliferative activity at all cell positions compared with samples taken more than 5 cm from a tumour. This is illustrated by the average LI, which is about 5.4% in the colon adjacent to a tumour compared with 10% distant; comparable values for the rectum are 4.6% and 8.5%. Samples taken from two patients with polyposis coli show distributions with a significant difference in skewness compared with normal colon and a general shifting of the distribution to the right, that is to higher cell positions. There is a significant increase in the mean cell position and the position of the peak LI in the polyposis coli samples.
Evolution of the Eye Transcriptome under Constant Darkness in Sinocyclocheilus Cavefish
Authors: Fanwei Meng, Ingo Braasch, Jennifer B. Phillips, Xiwen Lin, Tom Titus, Chunguang Zhang, John H. Postlethwait
Journal: Molecular Biology and Evolution (2013)

In adaptating to perpetual darkness, cave species gradually lose eyes and body pigmentation and evolve alternatives for exploring their environments. Although troglodyte features evolved independently many times in cavefish, we do not yet know whether independent evolution of these characters involves common genetic mechanisms. Surface-dwelling and many cave-dwelling species make the freshwater teleost genus Sinocyclocheilus an excellent model for studying the evolution of adaptations to life in constant darkness. We compared the mature retinal histology of surface and cave species in Sinocyclocheilus and found that adult cavefish showed a reduction in the number and length of photoreceptor cells. To identify genes and genetic pathways that evolved in constant darkness, we used RNA-seq to compare eyes of surface and cave species. De novo transcriptome assemblies were developed for both species, and contigs were annotated with gene ontology. Results from cave-dwelling Sinocyclocheilus revealed reduced transcription of phototransduction and other genes important for retinal function. In contrast to the blind Mexican tetra cavefish Astyanax mexicanus, our results on morphologies and gene expression suggest that evolved retinal reduction in cave-dwelling Sinocyclocheilus occurs in a lens-independent fashion by the reduced proliferation and downregulation of transcriptional factors shown to have direct roles in retinal development and maintenance, including cone-rod homeobox (crx) and Wnt pathway members. These results show that the independent evolution of retinal degeneration in cavefish can occur by different developmental genetic mechanisms.
Malaria morbidity and pyrethroid resistance after the introduction of insecticide-treated bednets and artemisinin-based combination therapies: a longitudinal study
Authors: Jean-François Trape, Adama Tall, Nafissatou Diagne, Ousmane Ndiath, Alioune B Ly, Joseph Faye, Fambaye Dieye-Ba, Clémentine Roucher, Charles Bouganali, Abdoulaye Badiane, Fatoumata Diene Sarr, Catherine Mazenot, Aïssatou Touré-Baldé, Didier Raoult, Pierre Druilhe, Odile Mercereau-Puijalon, Christophe Rogier, Cheikh Sokhna
Journal: The Lancet Infectious Diseases (2011)
Improved early identification of arthritis: evaluating the efficacy of Early Arthritis<i>Recognition</i>Clinics
Authors: Jessica A B van Nies, Elisabeth Brouwer, Floris A van Gaalen, Cornelia F Allaart, Tom W J Huizinga, Marcel D Posthumus, Annette H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> Only 31% of Dutch rheumatoid arthritis (RA)-patients visit a rheumatologist within 12 weeks after symptom onset; this is mainly due to delay at the level of the general practitioner (GP). In order to reduce delay of GPs in identifying early arthritis, we initiated an Early Arthritis <i>Recognition</i> Clinic (EA<i>R</i>C). <h3>Methods</h3> EA<i>R</i>Cs were initiated at the Leiden and Groningen University Medical Centers. At this EA<i>R</i>C, patients filled in a questionnaire about their symptoms, followed by a short visit with only a full joint examination by an experienced rheumatologist. If arthritis was present the patient got an appointment the same week at the regular outpatient clinic. The main outcome parameter was the GP-delay; the secondary outcome parameter was the total delay. In both centres, patients included in early arthritis clinics that had arrived via regular referrals served as control group. <h3>Results</h3> Four hundred patients visited the Leiden EA<i>R</i>C and 212 patients the Groningen EA<i>R</i>C. Arthritis was detected in 42% and 49% respectively. The median GP-delay for these arthritis patients was 2.0 (0.4–7.3) and 2.0 (0.4–10.0) weeks and the median total delay 8.6 (3.6–22.3) and 10.6 (3.1–30.8) weeks respectively. At these two clinics 59% and 51% of all arthritis patients and 65% and 53% of the patients that were subsequently diagnosed with undifferentiated arthritis or RA were seen within 12 weeks after symptom onset. In the Leiden and Groningen control groups that arrived via regular referrals, only 32% and 38% were seen within 12 weeks time. <h3>Conclusions</h3> The EA<i>R</i>C increased the early identification of arthritis and RA.
Image-Guided Enzyme/Prodrug Cancer Therapy
Authors: Cong Li, Marie-France Penet, Paul Winnard, Dmitri Artemov, Zaver M. Bhujwalla
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The success of enzyme/prodrug cancer therapy is limited by the uncertainty in the delivery of the enzyme in vivo. This study shows the use of noninvasive magnetic resonance (MR) and optical imaging to image the delivery of a prodrug enzyme. With this capability, prodrug administration can be timed so that the enzyme concentration is high in the tumor and low in systemic circulation and normal tissue, thereby minimizing systemic toxicity without compromising therapeutic efficiency. Experimental Design: The delivery of a multimodal imaging reporter functionalized prodrug enzyme, cytosine deaminase, was detected by MR and optical imaging in MDA-MB-231 breast cancer xenografts. Stability of the enzyme in the tumor was verified by 19F MR spectroscopy, which detected conversion of 5-fluorocytosine to 5-flurouracil. The optimal time window for prodrug injection determined by imaging was validated by immunohistochemical, biodistribution, and high-performance liquid chromatographic studies. The therapeutic effect and systemic toxicity of this treatment strategy were investigated by histologic studies and tumor/body weight growth curves. Results: The delivery of the functionalized enzyme in tumors was successfully imaged in vivo. The optimal time window for prodrug administration was determined to be 24 h, at which time the enzyme continued to show high enzymatic stability in tumors but was biodegraded in the liver. Significant tumor growth delay with tolerable systemic toxicity was observed when the prodrug was injected 24 h after the enzyme. Conclusion: These preclinical studies show the feasibility of using a MR-detectable prodrug enzyme to time prodrug administration in enzyme/prodrug cancer therapy.
Pertuzumab Protects the Achilles' Heel of Trastuzumab—Emtansine
Authors: William R. Gwin, Neil L. Spector
Journal: Clinical Cancer Research (2013)

Trastuzumab emtansine (T-DM1) represents a significant advancement in the treatment of HER2(+) breast cancers. Its clinical efficacy however will be limited by the development of therapeutic resistance. In this report, the HER3 ligand neuregulin is shown to mediate T-DM1 resistance, which was overcome by administration of pertuzumab, a steric inhibitor of HER2 dimerization.
The Lectin-like Receptor KLRE1 Inhibits Natural Killer Cell Cytotoxicity
Authors: Ingunn H. Westgaard, Erik Dissen, Knut M. Torgersen, Sasha Lazetic, Lewis L. Lanier, Joseph H. Phillips, Sigbjørn Fossum
Journal: The Journal of Experimental Medicine (2003)

We report the cloning and functional characterization in the mouse and the rat of a novel natural killer (NK) cell receptor termed KLRE1. The receptor is a type II transmembrane protein with a COOH-terminal lectin-like domain, and constitutes a novel KLR family. Rat Klre1 was mapped to the NK gene complex. By Northern blot and flow cytometry using newly generated monoclonal antibodies, KLRE1 was shown to be expressed by NK cells and a subpopulation of CD3+ cells, with pronounced interstrain variation. Western blot analysis indicated that KLRE1 can be expressed on the NK cell surface as a disulphide-linked dimer. The predicted proteins do not contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) or a positively charged amino acid in the transmembrane domain. However, in a redirected lysis assay, the presence of whole IgG, but not of F(ab′)2 fragments of a monoclonal anti-KLRE1 antibody inhibited lysis of Fc-receptor bearing tumor target cells. Moreover, the tyrosine phosphatase SHP-1 was coimmunoprecipitated with KLRE1 from pervanadate-treated interleukin 2–activated NK cells. Together, our results indicate that KLRE1 may form a functional heterodimer with an as yet unidentified ITIM-bearing partner that recruits SHP-1 to generate an inhibitory receptor complex.
THE TOXIC ACTION OF PREPARATIONS CONTAINING THE OXYGEN-LABILE HEMOLYSIN OF STREPTOCOCCUS PYOGENES
Authors: Alan W. Bernheimer, G. L. Cantoni
Journal: The Journal of Experimental Medicine (1947)

1. The susceptibility of mice to the lethal effect of preparations containing the oxygen-labile hemolysin (streptolysin O) of group A hemolytic streptococci has been studied. Injection of a single sublethal dose of the streptococcal preparation causes the development of resistance to the effect of a lethal dose injected subsequently. 2. Resistance is demonstrable 3 to 6 hours after the injection of the streptococcal preparation, persists for approximately 30 hours, and then disappears. 3. Resistance induced by the streptococcal preparation, although relatively specific, is directed not only against the streptococcal preparation but also against saponin. Mice made refractory to the streptococcal preparation and to saponin exhibit normal susceptibility to a number of other toxic agents, with the possible exception of the alpha toxin of Cl. welchii. 4. Mice injected with a sublethal dose of saponin develop resistance to the effect of a lethal dose of either saponin or the streptococcal preparation. 5. Resistance depends upon processes distinct from those underlying classical antitoxic immunity.
Stimulation of NOD1 induces RIP2, TAK1 and p38 MAPK dependent pro-inflammatory signalling in human lung microvascular endothelial cells
Authors: Timothy L. Gatheral, Laura Moreno, Daniel M. Reed, Rekha Badiger, Lucy K. Bailey, Neil Galloway-Phillipps, Jane A. Mitchell
Journal: European Respiratory Journal (2011)

Gram-negative bacteria are an important cause of septic shock. NOD1 receptors recognise peptidoglycan in the bacterial cell wall and initiate pro-inflammatory responses. We have previously shown in rodents that stimulation of NOD1 induces vascular dysfunction in vitro and profound shock in vivo . In this study we investigated the role of NOD1 in human lung microvascular endothelial cells (HMVEC) which represent a site of key importance in the pathophysiology of sepsis and acute lung injury.

HMVEC from healthy donors were cultured in 96-well plates. Cells were treated for 24 hours with vehicle ± LPS (TLR4) or iE-DAP (NOD1). In additional experiments cells were pre-treated for 1 hour with specific signalling inhibitors prior to addition of agonists (n=4-5). Cell activation was assessed by multiplex ELISA and by specific ELISAs for CXCL8 and 6-keto Prostaglandin F1α.

iE-DAP induced significant release of CXCL8, 6-Keto Prostaglandin F1α, IL-1β, IL-2, and IFNγ. 5Z-7-oxo-zeaenol or BIRB0796 similarly inhibited responses to iE-DAP (Figure 1) or LPS (P<0.05;two-way ANOVA). By contrast, PP2 was more potent an inhibitor of iE-DAP (Figure 1) than LPS (p<0.05; two-way ANOVA).

![Figure][1] 

Figure 1





In conclusion NOD1 is active in human microvascular endothelium and converges with TLR4 signalling at the level of TAK1 and p38 MAPK. NOD1 thus represents a potential target in the treatment of gram-negative sepsis.

 [1]: pending:yes
TERMINATION OF TOLERANCE TO HUMAN GAMMA GLOBULIN IN MICE BY ANTIGEN AND BACTERIAL LIPOPOLYSACCHARIDE (ENDOTOXIN)
Authors: Jacques M. Chiller, William O. Weigle
Journal: The Journal of Experimental Medicine (1973)

Bacterial lipopolysaccharides (endotoxin) allowed the circumvention of the thymus-derived (T) cell helper function otherwise required for the antibody response in mice to human gamma globulin (HGG). In an analogous fashion, the state of tolerance to HGG, existing at a time when bone marrow-derived (B) cells had lost their unresponsiveness, could be terminated by the injection of both immunogenic HGG and endotoxin, but by neither given alone. However, no effect on tolerance to HGG could be observed when this regimen was followed at a time when B cells were tolerant. After the spontaneous recovery from tolerance in B cells, it seemed that specific priming was occurring in that population. This phenomenon was observed either by the injection of endotoxin and HGG or by the adoptive transfer of cells into irradiated hosts. These data have been discussed in the light of potential autoimmune manifestations that could theoretically follow a simultaneous gram-negative bacterial infection along with a release of self-antigen.
Effects of tobacco smoking on findings in chest computed tomography among asbestos-exposed workers
Authors: T. Vehmas, L. Kivisaari, M.S. Huuskonen, M.S. Jaakkola
Journal: European Respiratory Journal (2003)

This study examined the effects of smoking on the findings in chest computed tomography (CT) in 587 asbestos-exposed construction workers (11 females, 576 males, mean age 62 yrs; 18 never-smokers, 406 exsmokers and 163 current smokers). The workers were imaged with spiral CT and high-resolution CT. A total of 13 radiological signs were scored by three radiologists independently. The workers' medical data, smoking habits and occupational exposures were collected at an interview. The effects of smoking status and smoked pack-yrs (0–87.5) on the CT signs were studied using multivariate analysis adjusted for confounding factors. Smoking increased all emphysema signs and contributed to bronchial wall thickening. Smoking was negatively associated with curvilinear and septal lines as well as with parenchymal bands. In persons who had smoked &lt;10 pack-yrs, smoking was positively related to paraseptal emphysema and to bronchial wall thickening and negatively related to septal lines, subpleural nodules and honeycombing. Smoking was related to several abnormal computed tomography signs even among those with relatively small exposure. Computed tomography can detect changes due to smoking at an early stage.
High Dietary Acid Load Predicts ESRD among Adults with CKD
Authors: Tanushree Banerjee, Deidra C. Crews, Donald E. Wesson, Anca M. Tilea, Rajiv Saran, Nilka Ríos-Burrows, Desmond E. Williams, Neil R. Powe
Journal: Journal of the American Society of Nephrology (2015)

Small clinical trials have shown that a reduction in dietary acid load (DAL) improves kidney injury and slows kidney function decline; however, the relationship between DAL and risk of ESRD in a population-based cohort with CKD remains unexamined. We examined the association between DAL, quantified by net acid excretion (NAEes), and progression to ESRD in a nationally representative sample of adults in the United States. Among 1486 adults with CKD age≥20 years enrolled in the National Health and Nutrition Examination Survey III, DAL was determined by 24-h dietary recall questionnaire. The development of ESRD was ascertained over a median 14.2 years of follow-up through linkage with the Medicare ESRD Registry. We used the Fine-Gray competing risks method to estimate the association of high, medium, and low DAL with ESRD after adjusting for demographics, nutritional factors, clinical factors, and kidney function/damage markers and accounting for intervening mortality events. In total, 311 (20.9%) participants developed ESRD. Higher levels of DAL were associated with increased risk of ESRD; relative hazards (95% confidence interval) were 3.04 (1.58 to 5.86) for the highest tertile and 1.81 (0.89 to 3.68) for the middle tertile compared with the lowest tertile in the fully adjusted model. The risk of ESRD associated with DAL tertiles increased as eGFR decreased (P trend=0.001). Among participants with albuminuria, high DAL was strongly associated with ESRD risk (P trend=0.03). In conclusion, high DAL in persons with CKD is independently associated with increased risk of ESRD in a nationally representative population.