tbuckley/cabot-search huggingface dataset:
Distinct Patterns of Dysregulated Expression of Enzymes Involved in Androgen Synthesis and Metabolism in Metastatic Prostate Cancer Tumors
Authors: Nicholas Mitsiades, Clifford C. Sung, Nikolaus Schultz, Daniel C. Danila, Bin He, Vijay Kumar Eedunuri, Martin Fleisher, Chris Sander, Charles L. Sawyers, Howard I. Scher
Journal: Cancer Research (2012)

Androgen receptor (AR) signaling persists in castration-resistant prostate carcinomas (CRPC), because of several mechanisms that include increased AR expression and intratumoral androgen metabolism. We investigated the mechanisms underlying aberrant expression of transcripts involved in androgen metabolism in CRPC. We compared gene expression profiles and DNA copy number alteration (CNA) data from 29 normal prostate tissue samples, 127 primary prostate carcinomas (PCa), and 19 metastatic PCas. Steroidogenic enzyme transcripts were evaluated by quantitative reverse transcriptase PCR in PCa cell lines and circulating tumor cells (CTC) from CRPC patients. Metastatic PCas expressed higher transcript levels for AR and several steroidogenic enzymes, including SRD5A1, SRD5A3, and AKR1C3, whereas expression of SRD5A2, CYP3A4, CYP3A5, and CYP3A7 was decreased. This aberrant expression was rarely associated with CNAs. Instead, our data suggest distinct patterns of coordinated aberrant enzyme expression. Inhibition of AR activity by itself stimulated AKR1C3 expression. The aberrant expression of the steroidogenic enzyme transcripts was detected in CTCs from CRPC patients. In conclusion, our findings identify substantial interpatient heterogeneity and distinct patterns of dysregulated expression of enzymes involved in intratumoral androgen metabolism in PCa. These steroidogenic enzymes represent targets for complete suppression of systemic and intratumoral androgen levels, an objective that is supported by the clinical efficacy of the CYP17 inhibitor abiraterone. A comprehensive AR axis-targeting approach via simultaneous, frontline enzymatic blockade, and/or transcriptional repression of several steroidogenic enzymes, in combination with GnRH analogs and potent antiandrogens, would represent a powerful future strategy for PCa management.
The Th2/Th17 Predominant Endotype of Severe Asthma Is Associated with Increased IL1β, C3 and Their Downstream Signaling Molecules in Bronchoalveolar Lavage
Authors: Rafeul Alam, Iram Zafar, Chaoyu Irvin, Yingfang Song, James Good, Donald Rollins, Magdalena M. Gorska, Richard J. Martin
Journal: Journal of Allergy and Clinical Immunology (2015)
Effects of Interleukin-2 Treatment on CD1d-Restricted Natural Killer T Cells
Authors: Johan K. Sandberg, Markus Moll
Journal: Clinical Cancer Research (2007)

To the Editor: Interleukins (IL) are potent biomolecules used for immunotherapy in cancer and infectious diseases. The clinical benefit of cytokines is linked to their strong effects on immune cells, and these effects are important to study in patients undergoing treatment because the cellular
Advance Directives and Outcomes of Surrogate Decision Making before Death
Authors: Maria J. Silveira, Scott Y.H. Kim, Kenneth M. Langa
Journal: New England Journal of Medicine (2010)

Recent discussions about health care reform have raised questions regarding the value of advance directives.We used data from survey proxies in the Health and Retirement Study involving adults 60 years of age or older who had died between 2000 and 2006 to determine the prevalence of the need for decision making and lost decision-making capacity and to test the association between preferences documented in advance directives and outcomes of surrogate decision making.Of 3746 subjects, 42.5% required decision making, of whom 70.3% lacked decision-making capacity and 67.6% of those subjects, in turn, had advance directives. Subjects who had living wills were more likely to want limited care (92.7%) or comfort care (96.2%) than all care possible (1.9%); 83.2% of subjects who requested limited care and 97.1% of subjects who requested comfort care received care consistent with their preferences. Among the 10 subjects who requested all care possible, only 5 received it; however, subjects who requested all care possible were far more likely to receive aggressive care as compared with those who did not request it (adjusted odds ratio, 22.62; 95% confidence interval [CI], 4.45 to 115.00). Subjects with living wills were less likely to receive all care possible (adjusted odds ratio, 0.33; 95% CI, 0.19 to 0.56) than were subjects without living wills. Subjects who had assigned a durable power of attorney for health care were less likely to die in a hospital (adjusted odds ratio, 0.72; 95% CI, 0.55 to 0.93) or receive all care possible (adjusted odds ratio, 0.54; 95% CI, 0.34 to 0.86) than were subjects who had not assigned a durable power of attorney for health care.Between 2000 and 2006, many elderly Americans needed decision making near the end of life at a time when most lacked the capacity to make decisions. Patients who had prepared advance directives received care that was strongly associated with their preferences. These findings support the continued use of advance directives.
Toll-Like Receptor 2 Mediates Apolipoprotein CIII–Induced Monocyte Activation: Retracted
Authors: Akio Kawakami, Mizuko Osaka, Masanori Aikawa, Satoshi Uematsu, Shizuo Akira, Peter Libby, Kentaro Shimokado, Frank M. Sacks, Masayuki Yoshida
Journal: Circulation Research (2008)

Apolipoprotein (apo)CIII predicts risk for coronary heart disease. We recently reported that apoCIII directly activates human monocytes. Recent evidence indicates that toll-like receptor (TLR)2 can contribute to atherogenesis through transduction of inflammatory signals. Here, we tested the hypothesis that apoCIII activates human monocytoid THP-1 cells through TLR2. ApoCIII induced the association of TLR2 with myeloid differentiation factor 88, activated nuclear factor (NF)-κB in THP-1 cells, and increased their adhesion to human umbilical vein endothelial cells (HUVECs). Anti-TLR2 blocking antibody, but not anti-TLR4 blocking antibody or isotype-matched IgG, inhibited these processes ( P &lt;0.05). ApoCIII bound with high affinity to human recombinant TLR2 protein and showed a significantly higher ( P &lt;0.05) and saturable binding to 293 cells overexpressing human TLR2 than to parental 293 cells with no endogenous TLR2. Overexpression of TLR2 in 293 cells augmented apoCIII-induced NF-κB activation and β 1 integrin expression, processes inhibited by anti-apoCIII antibody as well as anti-TLR2 antibody. Exposure of peripheral blood monocytes isolated from C57BL/6 (wild-type) mice to apoCIII activated their NF-κB and increased their adhesiveness to HUVECs. In contrast, apoCIII did not activate monocytes from TLR2-deficient mice. Finally, intravenous administration to C57BL/6 mice of apoCIII-rich very-low-density lipoprotein (VLDL), but not of apoCIII-deficient VLDL, activated monocytes and increased their adhesiveness to HUVECs, processes attenuated by anti-TLR2 or anti-apoCIII antibody. ApoCIII-rich VLDL did not activate monocytes from TLR2-deficient mice. In conclusion, apoCIII activated monocytes at least partly through a TLR2-dependent pathway. The present study identifies a novel mechanism for proinflammatory and proatherogenic effects of apoCIII and a role for TLR2 in atherosclerosis induced by atherogenic lipoproteins.
Experimental colonic carcinogenesis: changes in faecal bile acids after promotion of intestinal tumours by small bowel resection in the rat.
Authors: A P Savage, M S Sian, J L Matthews, S R Bloom, T Cooke
Journal: Gut (1988)

Small bowel resection promotes the development of colonic tumours in azoxymethane treated rats. As high faecal bile acid concentrations are associated with colonic cancer and may be altered by resection, we have studied changes in faecal bile acid concentrations during promotion of colonic carcinogenesis by increasing small bowel resection. Twenty rats in each group underwent either jejunal transection or 20%, 50%, or 80% proximal small bowel resection. Tumours were induced with azoxymethane 10 mg/kg by 12 weekly subcutaneous injections, and faecal bile acid concentrations were measured at six and 16 weeks. Colonic tumour number rose from 0.6 per rat in the transection group to 1.6 per rat in the 50% resection group (p less than 0.01) but were not significantly different to transection values at 0.8 per rat in the 80% resection group. Total daily faecal bile acid excretion and bile acid concentrations fell with increasing resection from 14.2 (1.6) mg/rat/day and 5.8 (0.7) mg/g dry faeces respectively in the transection group to 6.5 (0.5) mg/rat/day and 2.9 (0.2) mg/g respectively in the 80% resection group (p less than 0.001). The greatest reduction was seen in the concentration of deoxycholic acid which has been particularly associated with the aetiology of colonic cancer. The promotion of colonic tumours following small bowel resection in carcinogen treated rats is unlikely to be mediated by changes in faecal bile acid concentration or composition.
Rationale and design of the <scp>SOluble</scp> guanylate Cyclase <scp>stimulatoR</scp> in <scp>heArT failurE</scp> Studies (<scp>SOCRATES</scp>)
Authors: Burkert Pieske, Javed Butler, Gerasimos Filippatos, Carolyn Lam, Aldo Pietro Maggioni, Piotr Ponikowski, Sanjiv Shah, Scott Solomon, Elisabeth Kraigher‐Krainer, Eliana Tibana Samano, Andrea Viviana Scalise, Katharina Müller, Lothar Roessig, Mihai Gheorghiade
Journal: European Journal of Heart Failure (2014)
Degree and time sequence of hypothermic protection against experimental ischemic acute renal failure.
Authors: R A Zager, D J Gmur, C R Bredl, M J Eng
Journal: Circulation Research (1989)

The purpose of this study was to assess the degree, time sequence, and biochemical correlates of hypothermic protection against ischemic acute renal failure. Rats subjected to 40 minutes of bilateral renal artery occlusion (RAO) were made mildly hypothermic (32 degrees-33 degrees C, by cold saline peritoneal lavage) during the following time periods: 1) RAO only, 2) reperfusion only (beginning at 0, 15, 30, or 60 minutes after RAO and maintained for 45 minutes), or 3) during and after (0-45 minutes) RAO. Continuously normothermic (37 degrees C) RAO rats served as controls. The control rats developed severe acute renal failure (blood urea nitrogen [BUN], 95 +/- 4 mg/dl; creatinine, 2.2 +/- 0.1 mg/dl; and extensive tubular necrosis at 24 hours). Hypothermia confined to RAO was highly protective (BUN, 33 +/- 5 mg/dl; creatinine, 0.62 +/- 0.07 mg/dl; and minimal necrosis). Hypothermia partially preserved ischemic renal adenylate high-energy phosphate (ATP and ADP), increased AMP and inosine monophosphate concentrations, and lessened hypoxanthine/xanthine buildup (assessed at end of RAO). Hypothermia confined to the reflow period (beginning at 0, 15, and 30 minutes) was only mildly protective (e.g., BUN, 58-63 mg/dl); the degree of protection did not differ according to the time of hypothermic onset. Lowering reflow temperature to 26 degrees C had no added benefit. Hypothermia that started at 60 minutes after RAO conferred no protection. Combining ischemic and postischemic hypothermia abolished all renal failure (assessed at 24 hours). This study offers the following conclusions: Mild hypothermia can totally prevent experimental ischemic acute renal failure. Hypothermia is highly effective during ischemia, and it is mildly protective during early reflow; these benefits are additive. During early reflow, hypothermic protection is not critically time dependent. By 60 minutes of reflow, no effect is elicited; this absence of effect possibly signals completion of the reperfusion injury process. Hypothermia's protective effects may be mediated, in part, by improvements in renal adenine nucleotide content and, possibly, by decreasing postischemic oxidant stress.
Does complex behaviour imply complex cognitive abilities?
Authors: Kenny R. Coventry, John Clibbens
Journal: Behavioral and Brain Sciences (2002)

In this commentary, we propose that the shifts in symmetry Wynn documents may be explained in terms of simpler mechanisms than he suggests. Furthermore, we argue that it is dangerous to draw definitive conclusions about the cognitive abilities of a species from the level of symmetry observed in the artefacts produced by that species.
Dyschromatosis symmetrica hereditaria (reticulate acropigmentation of Dohi): report of a Japanese family with the condition and a literature review of 185 cases
Authors: None OYAMA, None SHIMIZU, None OHATA, None TAJIMA, None NISHIKAWA
Journal: British Journal of Dermatology (1999)

We report a Japanese family with dyschromatosis symmetrica hereditaria (DSH) (MIM 127400 in McKusick's Mendelian Inheritance in Man), a rare autosomal dominant genodermatosis, predominantly occurring among Japanese and Korean individuals. Members of the present family affected with the disease showed a mixture of hyperpigmented and hypopigmented macules distributed on the face and the dorsal aspects of the extremities, which are typical of DSH. As most of the literature on DSH has been written in Japanese, dermatologists outside Japan are not familiar with the condition. In this paper, 185 cases of DSH, most of them reported in Japanese, are reviewed and unique clinical, histological and genetic features of this condition are delineated.
Clinical characteristics and prognosis of respiratory viral agents in hospitalized children during one Year period
Authors: Esra Toprak Kanik, Ozge Yilmaz, Ahmet Turkeli, Tuker Borucu, Tamer Sanlidag, Hasan Yuksel
Journal: European Respiratory Journal (2013)

Introduction:  Clinical findings and prognosis may differ among various respiratory viral agents associated with acute and recurrent respiratory problems. The aim of the present study was to determine the viral etiological agents in children hsopitalized for respiratory findings in a tertiary care center betwen September 2011 and 2012.   Methods:  All hospitalized children with bronchiolitis were enrolled between September 2011 and September 2012. Data regarding clinical characteristics and severity of bronchiolitis as well as routine laboratory findings such as leukocyte count and C-reactive protein (CRP) were recorded at enrollment. Nasal swabs were obtained from all children for respiratory viral detection by PCR multiplex.   Results:  Total of 275 children aged between 2 and 72 months (mean (SD)= 17.8(15.9)) were enrolled. Viral agent was detected in 31.6% of the patients and rhinovirus, RSV, influenza nad parainfluenza were the most commonly detected viruses (8.7%, 6.2 %, 4.7%, 4.0% respectivly). Viral agent detected wasn’t affected by familial smoking or siblings but parainfluenze virus was more common in children attending day care (14.8% vs 4.8%, p=0.04). Rhinoviruses were more common among children without compared to with fever (15% vs 2%, p=0.01). Days of hospitalization differed significantly according to the viral agent (p=0.006). Recurrence of wheezing was not significantly different among children with different viral etiological agents (p=0.95).   Conclusion:  Daycare attendance influences the viral etiological agent. Fever and duration of hospitalization differ among different viral agents but recurrence of bronchiolitis is independent of the viral agent.
Rapid improvement of nailfold capillaroscopy after intense immunosuppression for systemic sclerosis and mixed connective tissue disease
Authors: M Aschwanden, T Daikeler, K A Jaeger, C Thalhammer, A Gratwohl, M Matucci-Cerinic, A Tyndall
Journal: Annals of the Rheumatic Diseases (2008)

Systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are both associated with microvascular pathology. The most striking early clinical manifestation is Raynaud phenomenon (RP), which is only partly caused by functional narrowing of small vessels. Moreover, alteration of endothelial function1 and impairment of endothelial progenitor cell function in these patients have been previously described.2 This may have an important impact on capillary pathology. The resulting morphological changes can be observed by nailfold capillaroscopy (NFC). Haemorrhages, giant capillaries and avascular regions are typical findings that cannot only be detected by NFC, but also, at least in part, with moderate to substantial reliability using simpler methods such as ophthalmoscopes or dermatoscopes.3 These findings …
THE INHIBITION OF SURFACE PHAGOCYTOSIS BY THE CAPSULAR "SLIME LAYER" OF PNEUMOCOCCUS TYPE III
Authors: W. Barry Wood, Mary Ruth Smith
Journal: The Journal of Experimental Medicine (1949)

Five strains of type III pneumococcus have been shown to possess wide capsular slime layers during the logarithmic phase of growth in serum broth. The slime layer stains metachromatically with methylene blue and can be visualized under the electron microscope as a fuzzy halo which extends well beyond the surace of the capsule proper and causes centrifugates of the organism to be of extremely large volume. This outer capsular structure is most readily demonstrated in vivo and in nutrient broth containing glucose and serum. It disappears from the surface of the cell with aging of the culture, and is easily removed by dilute alkali, alcohol, and heat. Exposure of slime-covered type III pneumococci to homologous antibody and to type III polysaccharidase reveals that the slime layer contains the same type-specific polysaccharide that is present in the rest of the capsule. From a type III strain producing a prominent slime layer an intermediate mutant has been isolated which forms small non-mucoid colonies on blood agar and possesses a relatively small capsule with a barely discernible slime layer. The wide slime layer protects virulent type III pneumococci from surface phagocytosis. Whenever the type III cells lose their broad slime layer, whether from aging of the culture, from mutation, from exposure to injurious chemicals, or from the action of type III polysaccharidase, they become susceptible to phagocytosis by the surface mechanism. Once phagocyted the type III pneumococci are promptly destroyed, even in the absence of antibodies.
Costly Cancer Drugs Trigger Proposals To Modify Clinical Trial Design
Authors: C. Schmidt
Journal: JNCI Journal of the National Cancer Institute (2009)

The dilemma over high cancer drug costs was evident during a telling moment at the American Society of Clinical Oncology’s annual meeting last June. At issue was Genentech’s phase III study with bevacizumab (Avastin), an antiangiogenic treatment that can cost up to $9,000 per month in patients with earlystage colorectal cancer. Norman Wolmark, M.D., chair of the National Surgical Adjuvant Breast and Bowel Project (NSABP), was on hand to report the results. And they were disappointing to many: The trial, NSABP C-08, had failed to extend disease-free survival after 3 years ’ follow-up. But Wolmark wasn’t giving up on the treatment yet. Emphasizing that the trial had achieved a “transient but robust benefi t in [disease-free survival] during the 1 year that bevacizumab was utilized,” he concluded that consideration should be given to another trial to look at longer use of bevacizumab. Asked in the press conference about the cost of the drug over a long period, Wolmark replied that cost was not a researcher’s concern. “Ask the drug company,” he said.
Genetic-based dosing in orthopedic patients beginning warfarin therapy
Authors: Eric A. Millican, Petra A. Lenzini, Paul E. Milligan, Leonard Grosso, Charles Eby, Elena Deych, Gloria Grice, John C. Clohisy, Robert L. Barrack, R. Stephen J. Burnett, Deepak Voora, Susan Gatchel, Amy Tiemeier, Brian F. Gage
Journal: Blood (2007)
Feedback inhibition of insulin gene expression by insulin.
Authors: L Koranyi, D E James, E W Kraegen, M A Permutt
Journal: Journal of Clinical Investigation (1992)

To examine the possible involvement of insulin and glucose in regulation of pancreatic islet gene expression, hyperinsulinemic (insulin infusion 4.1 mU/kg per min) clamps were performed for 12 h in rats at two different levels of glycemia (either 3 or 8 mM). A control group received a saline infusion for 12 h. At the end of the 12-h study period, pancreatic RNA was extracted, proinsulin and amylin mRNAs were measured on total RNA, and glucokinase and glucose transporter (GLUT-2) mRNAs were measured on poly(A)+ RNA by dot blot analysis. In insulin-infused hypoglycemic rats, there was a 58% decrement in proinsulin mRNA (P less than 0.01) relative to levels in controls, with no change in amylin, glucokinase, or islet GLUT-2 mRNAs. In insulin-infused hyperglycemic rats, there was a comparable decrement (44%, P less than 0.01) in proinsulin mRNA and a smaller decrement in GLUT-2 mRNA (32%, P less than 0.05), with no change in amylin or glucokinase mRNAs relative to levels in control animals. These studies suggest that insulin has a negative feedback inhibitory effect on its own synthesis. The mechanism of inhibition is unknown. It could be a direct effect of insulin on its own transcription, or alternatively an indirect effect mediated by humoral or neural factors. Sustained hyperinsulinemia may lead to suppression of normal islet beta cells and may contribute to the ultimate hypoinsulinemia of noninsulin-dependent diabetes mellitus.
PUBLIC IMAGES OF PSYCHIATRY: CHALLENGES IN PLANNING COMMUNITY MENTAL HEALTH CARE
Authors: MARVIN E. PERKINS, ELENA PADILLA, JACK ELINSON
Journal: American Journal of Psychiatry (1965)

Some findings from a survey of the public image of mental health services in New York City reveal that: 1. A majority of New Yorkers claim personal acquaintance with one or more persons who have been under professional care for mental problems. 2. Half of all adults report personal problems which they believe might have been helped by outside services. 3. The public image of the psychiatrist is confused on some points—nearly half the public does not know that the psychiatrist is a doctor of medicine. 4. Fewer New Yorkers know psychiatrists as friends or acquaintances than know other physicians, dentists, and nurses. 5. Psychiatrists are identified as professionals best able to deal with mental troubles; social workers are regarded as best able to deal with family troubles. 6. In the public's view, psychiatrists trists are deemed as interested in their patients and as successful in helping them as are other medical specialists. 7. Most persons believe that state mental hospitals serve to "protect the community," even if patients may not get better there. 8. Many regard state mental hospitals as being most like prisons, TB sanitoria or nursing homes; a minority of the public thinks of them as most like general hospitals. 9. More persons think the quality of care in a state mental hospital is "good" than think it "poor." However, the proportion who believe the quality of care is "good" in a state mental hospital is less than the proportion who believe that care is "good" in a general hospital. 10. Three in 4 say they are willing to have ex-mental hospital patients as co-workers and neighbors; but only 1 in 4 is willing to share an apartment with, or have someone in his family marry, an ex-mental hospital patient. 11. Community mental health services which provide quick assistance, such as telephone answering services, psychiatric emergency, and "walk-in" clinics, are generally approved by a larger proportion of the public than those which bring mental patients into relatively close contact with the community, such as family foster care and so-called day, night and open mental hospitals. Notwithstanding the latter, neighborhood aftercare and rehabilitation services for ex-mental hospital patients are also highly approved.