tbuckley/cabot-search huggingface dataset:
Targeting Mutant (V600E)<i>B-Raf</i>in Melanoma Interrupts Immunoediting of Leukocyte Functions and Melanoma Extravasation
Authors: Shile Liang, Arati Sharma, Hsin-Hsin Peng, Gavin Robertson, Cheng Dong
Journal: Cancer Research (2007)

Abstract Polymorphonuclear neutrophils (PMN) facilitate melanoma cell extravasation under dynamic flow conditions by the binding of intercellular adhesion molecule-1 (ICAM-1) on melanoma cells to β2 integrins on PMNs, which is mediated by endogenously produced chemokine interleukin 8 (IL-8) from the tumor microenvironment. However, little is known about the role of B-Raf, the most mutated gene in malignant melanomas, in this process. In this study, we investigated the functional importance of B-Raf in melanoma extravasation by using short interfering RNA to reduce expression/activity of mutant V600EB-Raf in melanoma. Results indicated that knockdown of mutant V600EB-Raf inhibited melanoma cell extravasation in vitro and subsequent lung metastasis development in vivo. Mechanistic studies showed that inhibition of V600EB-Raf significantly reduced the constitutive secretion of IL-8 from melanoma cells as well as the capacity of endogenous IL-8 production from the melanoma-PMN microenvironment. Furthermore, a reduction in ICAM-1 expression on melanoma cells was detected following mutant V600EB-Raf knockdown. Together, these results suggest that targeting mutant V600EB-Raf reduces melanoma cell extravasation by decreasing IL-8 production and interrupting ICAM-1-β2 integrin binding of melanoma cells to the endothelium mediated by PMNs in the microcirculation, which provides a rationale and mechanistic basis for targeting mutant V600EB-Raf to inhibit melanoma extravasation and subsequent metastasis development. [Cancer Res 2007;67(12):5814–20]
C6: synthesis by the liver in vivo.
Authors: M J Hobart, P J Lachmann, R Y Calne
Journal: The Journal of Experimental Medicine (1977)

The allotype of the sixth component of complement was determined in a patient before and after liver transplantation. The C6 phenotype changed from A before transplantation to B (the donor phenotype) within 10 days of the transplant and remained wholly of the donor phenotype at 17 wk. This demonstrates that the liver is the exclusive or predominant site of C6 synthesis in vivo in man.
Protruding the tongue improves posterior rhinomanometry in obstructive sleep apnoea syndrome
Authors: A Coste, F Lofaso, MP d'Ortho, B Louis, E Dahan, R Peynegre, A Harf
Journal: European Respiratory Journal (1999)

In posterior rhinomanometry (PRM), oropharyngeal pressure is measured using a tube placed between the tongue and the hard palate. For valid results the patient must position the tongue and soft palate so that both the oropharynx and nasopharynx remain open. A high rate of failure of conventional PRM has been reported in normal individuals. In patients with obstructive sleep apnoea syndrome (OSAS), upper airway abnormalities may further increase the failure rate. This study proposes a modification of the technique in which protrusion of the tongue enhances pressure transmission between the nasopharynx and the mouth. In eight normal subjects, resistance was similar when measured by both methods. Of 24 OSAS patients, conventional PRM was unsuccessful in 11. In the remaining 13 patients, a significant correlation between the two methods was found, but resistance was lower by "tongue-out" than by conventional PRM, consistent with a decrease, during tongue protrusion, in retropalatal resistance, which is a component of the "nasal" resistance measured by PRM. In 26 OSAS patients, unilateral nasal resistance values measured by "tongue-out" PRM were similar to those measured by anterior rhinomanometry. When the "tongue-out" method was used routinely in 541 snorers, failure rates were 1.1% in the 272 non-OSAS patients and 3.7% in the 269 OSAS patients. These results indicate that posterior rhinomanometry with tongue protrusion is a highly effective tool for measuring nasal resistance in snorers.
Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall
Authors: Christian Werner, Tobias Fürster, Thomas Widmann, Janine Pöss, Cristiana Roggia, Milad Hanhoun, Jürgen Scharhag, Nicole Büchner, Tim Meyer, Wilfried Kindermann, Judith Haendeler, Michael Böhm, Ulrich Laufs
Journal: Circulation (2009)

Background— The underlying molecular mechanisms of the vasculoprotective effects of physical exercise are incompletely understood. Telomere erosion is a central component of aging, and telomere-associated proteins regulate cellular senescence and survival. This study examines the effects of exercising on vascular telomere biology and endothelial apoptosis in mice and the effects of long-term endurance training on telomere biology in humans. Methods and Results— C57/Bl6 mice were randomized to voluntary running or no running wheel conditions for 3 weeks. Exercise upregulated telomerase activity in the thoracic aorta and in circulating mononuclear cells compared with sedentary controls, increased vascular expression of telomere repeat-binding factor 2 and Ku70, and reduced the expression of vascular apoptosis regulators such as cell-cycle–checkpoint kinase 2, p16, and p53. Mice preconditioned by voluntary running exhibited a marked reduction in lipopolysaccharide-induced aortic endothelial apoptosis. Transgenic mouse studies showed that endothelial nitric oxide synthase and telomerase reverse transcriptase synergize to confer endothelial stress resistance after physical activity. To test the significance of these data in humans, telomere biology in circulating leukocytes of young and middle-aged track and field athletes was analyzed. Peripheral blood leukocytes isolated from endurance athletes showed increased telomerase activity, expression of telomere-stabilizing proteins, and downregulation of cell-cycle inhibitors compared with untrained individuals. Long-term endurance training was associated with reduced leukocyte telomere erosion compared with untrained controls. Conclusions— Physical activity regulates telomere-stabilizing proteins in mice and in humans and thereby protects from stress-induced vascular apoptosis.
Reduction of Recurrent Ischemia With Abciximab During Continuous ECG-Ischemia Monitoring in Patients With Unstable Angina Refractory to Standard Treatment (CAPTURE)
Authors: Peter Klootwijk, Simon Meij, Rein Melkert, Timo Lenderink, Maarten L. Simoons
Journal: Circulation (1998)

Background —In the CAPTURE (c7E3 Fab Anti Platelet Therapy in Unstable REfractory angina) trial, 1265 patients with refractory unstable angina were treated with abciximab or placebo, in addition to standard treatment from 16 to 24 hours preceding coronary intervention through 1 hour after intervention. To investigate the incidence of recurrent ischemia and the ischemic burden, a subset of 332 patients (26%) underwent continuous vector-derived 12-lead ECG-ischemia monitoring. Methods and Results —Patients were monitored from start of treatment through 6 hours after coronary intervention. Ischemic episodes were detected in 31 (18%) of the 169 abciximab and in 37 (23%) of the 163 placebo patients (NS). Only 9 (5%) of abciximab versus 22 (14%) of placebo patients had ≥2 ST episodes ( P &lt;0.01). In patients with ischemia, abciximab significantly reduced total ischemic burden ( P &lt;0.02), which was calculated alternatively as the total duration of ST episodes per patient, the area under the curve of the ST vector magnitude during episodes, or the sum of the areas under the curves of 12 leads during episodes. Twenty-one patients (6%) suffered a myocardial infarction (MI) (18) or died (3) within 5 days of treatment. The presence of asymptomatic and symptomatic ST episodes during the monitoring period preceding coronary intervention was associated with an increased relative risk of these events of 3.2 (95% CI 1.4, 7.4) and 4.1 (95% CI 1.4, 12.2), respectively. Conclusions —Recurrent ischemia predicts MI or death within 5 days of follow-up. Treatment with abciximab is associated with a reduction of frequent ischemia and a reduction of total ischemic burden in patients with refractory unstable angina. As such, patients with ischemia derive particularly high benefit from abciximab.
Effects of parental smoking on the respiratory health of adults
Authors: M N Upton
Journal: Thorax (2004)

Further evidence that parental smoking may have long term effects into adulthood on the respiratory health of offspring

A paper on passive smoking by Cook and Strachan1 published in a Thorax review series in 1999 reported odds ratios (OR) for childhood lower respiratory tract illnesses, respiratory symptoms, and middle ear disease of 1.2–1.6 for either parent smoking, the risks usually being higher in pre-school children than in children of school age. The review concluded that parental smoking was causally associated with impaired lung function in children, but found inconsistent evidence linking parental smoking to allergic sensitisation and suggested that evidence linking maternal smoking to bronchial hyperresponsiveness (BHR) may have arisen from publication bias.1

There is little information from follow up studies about the effect on adult health of exposure to parental smoking,2,3 which is understandable given the logistical difficulties of following individuals for many decades from birth. In this issue of Thorax Svanes and colleagues take a short cut and report cross-sectional results from the European Community Respiratory Health Survey (ECRHS) linking recalled information about parental smoking to respiratory symptoms, asthma, forced expiratory volumes, and BHR in up to 18 688 adults aged 20–44 years from 37 centres in 17 countries.4

For men and women overall, maternal smoking was positively associated with wheeze (OR 1.12), with a composite variable of three or more asthma symptoms (OR 1.14), but not with current asthma. Because of the large sample, 95% confidence intervals were narrow and excluded unity despite excess risks of wheeze and asthma symptoms being low. The possibility that such weak effects may be due to confounding should be considered, although similar sized effects were found in never smokers. Maternal smoking was associated with a forced expiratory volume in 1 second (FEV1) 24 ml lower …
The Translational Journey of Brain β-Amyloid Imaging
Authors: Gil D. Rabinovici
Journal: JAMA Neurology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Curability of Tumors Bearing Herpes Thymidine Kinase Genes Transfered by Retroviral Vectors
Authors: F L Moolten, J M Wells
Journal: JNCI Journal of the National Cancer Institute (1990)

Retroviral vectors constructed to contain the herpes simplex virus thymidine kinase (HSV-TK) gene were used for transduction of this gene into murine sarcoma and lymphoma cells to yield sublines susceptible in vitro to the cytotoxicity of ganciclovir, a drug specifically activated by HSV-TK. In vivo, ganciclovir induced complete, durable regressions in most mice bearing transplanted HSV-TK-positive sarcomas; its efficacy against lymphomas was only marginal, possibly because of their greater instability of gene expression. The results imply the potential value of an anticancer strategy entailing the prophylactic use of retroviral vectors to create tissue mosaicism for drug sensitivity.
The Kidneys in the Bible
Authors: Garabed Eknoyan
Journal: Journal of the American Society of Nephrology (2005)

The kidneys, always used in the plural (kelayot), are mentioned more than 30 times in the Bible. In the Pentateuch, the kidneys are cited 11 times in the detailed instructions given for the sacrificial offering of animals at the altar. Whereas those instructions were for purification ceremonies at the Temple, sacrificial offerings were made subsequently in seeking divine intervention for the relief of medical problems. In the books of the Bible that follow the Pentateuch, mostly in Jeremiah and Psalms, the human kidneys are cited figuratively as the site of temperament, emotions, prudence, vigor, and wisdom. In five instances, they are mentioned as the organs examined by God to judge an individual. They are cited either before or after but always in conjunction with the heart as mirrors of the psyche of the person examined. There is also reference to the kidneys as the site of divine punishment for misdemeanors, committed or perceived, particularly in the book of Job, whose suffering and ailments are legendary. In the first vernacular versions of the Bible in English, the translators elected to use the term "reins" instead of kidneys in differentiating the metaphoric uses of human kidneys from that of their mention as anatomic organs of sacrificial animals burned at the altar. This initial effort at linguistic purity or gentility has progressed further in recent versions of the Bible, in which the reins are now replaced by the soul or the mind. The erosion may have begun in the centuries that followed the writing of the Bible, when recognition of the kidneys as excretory organs deprived them of the ancient aura of mysterious organs hidden deep in the body but accessible to the look of God. At approximately the same time, Greek analytical philosophy argued that the brain, which is never mentioned in the Bible, was the most divine and sacred part of the body. This argument gained ground in the past century, when the functions of the brain were elucidated, and ultimately established in the 1960s, when salvaging the kidneys for transplantation necessitated a change in the definition of death as irreversible brain function. It is ironic that advances in understanding kidney function and in nephrology that made kidney transplantation feasible may have contributed, albeit indirectly, to the gradual elimination of the metaphoric mention of human kidneys in the Bible.
Depressive Symptoms in a Trial Behavioral Family Systems Therapy for Diabetes: A Post Hoc Analysis of Change
Authors: Andrew R. Riley, Danny C. Duke, Kurt A. Freeman, Korey K. Hood, Michael A. Harris
Journal: Diabetes Care (2015)

OBJECTIVE The objective was to test whether Behavioral Family Systems Therapy for Diabetes (BFST-D), an evidence-based family therapy, produces individual changes in depressive symptoms for adolescents with type 1 diabetes in suboptimal glycemic control (HbA1c ≥9.0% [≥74.9 mmol/mol]). RESEARCH DESIGN AND METHODS Data were from a randomized controlled trial (RCT) comparing two modes of BFST-D delivery: in clinic versus Internet videoconferencing. There were no significant differences between groups in the RCT, so groups were collapsed into a within-group prepost design for secondary analyses. A multiple regression analysis was performed to test for mediation of treatment outcomes by changes in family processes. RESULTS Significant improvements in glycemic control, depressive symptoms, and family functioning were found from pre- to posttreatment. A multiple regression analysis for within-subject mediation indicated that improvements in depressive symptoms were partially mediated by improvements in parent-youth conflict; however, family process changes did not mediate diabetes health outcomes. CONCLUSIONS In addition to improving treatment adherence and glycemic control, BFST-D has collateral benefits on depressive symptoms.
The natural history of perianal disease
Authors: B. Hayee, V. E. Sayer, M. Kabir, S. Papagrigoriadis, G. Chung-Faye, I. Bjarnason, I. Forgacs
Journal: Gut (2011)

<h3>Introduction</h3> Perianal disease (PD; uncomplicated abscess and/or fistula) is a relatively common condition. There is a recognised association with Crohn9s disease (CD) and 11–26% of patients in paediatric1 and adult2 case series are purported to develop intestinal CD. However, the temporal relationship is unclear, as is the natural history of PD. <h3>Methods</h3> This was a single-centre (KCH) retrospective study with cohorts of patients having undergone medical or surgical therapy for PD since Jan 2008 (all after MRI) identified from theatre and electronic patient record databases (Galaxy and Unisoft). Case notes were then examined for the history, nature and length of follow-up of PD. Details of medical treatment were also obtained for patients with CD. <h3>Results</h3> 97 patients (24 F; 37.5±12.4 years) were identified with uncomplicated PD (having undergone surgical intervention), with 158 episodes of perianal sepsis, most frequently occurring in relation to an intersphincteric (34/97) or transphincteric (27/97) fistula. Median follow-up was 7.4 months (IQR 2.3–20.6). Of these, 8 patients (4 F; 25.4±11.6 years) went on to develop histologically proven intestinal CD, with a median time from presentation with PD of 4.3 (3.3–7.0) months. 30 patients (15 F; 37.6±13.7 years) with intestinal CD who then developed PD were also identified (49 episodes of perianal sepsis). Of these, 9 had PD at presentation and in the remainder it was first manifest after a median of 41.3 (17.6–90.4) months from diagnosis. <h3>Conclusion</h3> 8% of patients presenting with PD in this cohort went on to develop intestinal CD, which became evident shortly after surgical intervention. It is more common for patients with established CD to develop perianal disease and some do this after years of intestinal disease only.
PTH-135 Osteomyelitis In Adult Patients On Long-term Parenteral Nutrition
Authors: P Allan, P Stevens, P Chadwick, A Teubner, A Abraham, G Carlson, S Lal
Journal: Gut (2014)

<h3>Introduction</h3> Osteomyelitis (OM) has rarely been reported in association with central venous catheter (CVC) use, but there are no reported data on the prevalence of OM in patients with intestinal failure (IF) with long term CVCs for parenteral nutrition (PN). We assessed period prevalence and characteristics of OM in adult patients on home PN. <h3>Methods</h3> This was a retrospective study from a prospectively maintained database of patients referred to a national IF unit (IFU). Age, time on home PN, cultured organism (s) and OM site were recorded. Patients were divided into 2 groups: OM occurring in the context of acute (Type 2) IF (AIF) or chronic (Type 3) IF (CIF). Statistical analysis was Student’s t-test. <h3>Results</h3> 19 cases of OM occurred in 15 patients (6 male (40%)) between 2004–2013. There were 9 cases of OM in 9 patients with AIF, and 10 cases in 6 patients with CIF; the latter yielded a period prevalence for OM of 1.3% when compared to the 457 home PN (HPN) patients managed by the IFU over this period. There were no cases of OM in the preceding 9 years (1995–2004) at the IFU. Median (range) age at commencing PN was 66 (30–72) years in AIF compared to 64 (29–70) years in CIF and mean (95% CI) Charlson co-morbidity score was 3.7 (±2.5) in AIF compared to 2.2 (±0.9) in CIF. Patients with AIF had spent less time on PN before developing OM, compared to patients with CIF; despite this, the rate of CRBSIs was higher in the AIF than in the CIF group (see Table) as a result of patients with AIF contracting CRBSIs prior to specialised referral. Organisms and site of infection are shown in the table; identification of organism from the site of the OM successfully occurred in 3/9 (33%) cases in AIF and 3/10 (30%) cases in CIF, the remaining were identified via blood culture and aspiration of collections except one case where no organism was found, for which TB was suspected. All but one patient received at least 6 weeks antimicrobial chemotherapy; a further case required treatment for 3 months with antibiotics, 3 months with antifungals and 9 months with anti-TB medication. 4/10 (40%) AIF cases required operative stabilisation: 3 spinal and 1 above knee amputation. 2/10 (20%) CIF cases required operative stabilisation: 1 spinal and 1 pedal phalanx amputation. No patient died from OM. <h3>Conclusion</h3> This is the first report of OM in a large cohort of patients with IF. While OM in IF is rare, the present reported experience from a national referral centre suggests that it may be increasing in incidence. IF practitioners should be vigilant for OM as a source of sepsis in this complex group of patients, since it carries significant morbidity. <h3>Disclosure of Interest</h3> None Declared.
Uremia Accelerates both Atherosclerosis and Arterial Calcification in Apolipoprotein E Knockout Mice
Authors: Ziad A. Massy, Ognen Ivanovski, Thao Nguyen-Khoa, Jesus Angulo, Dorota Szumilak, Nadya Mothu, Olivier Phan, Michel Daudon, Bernard Lacour, Tilman B. Dru[Combining Diaeresis]eke, Martin S. Muntzel
Journal: Journal of the American Society of Nephrology (2004)

Chronic renal failure (CRF) favors the development of atherosclerosis and excessive calcification of atheromatous lesions. CRF was induced in apolipoprotein E knockout (apoE(-/-)) mice to study (1) a possible acceleration of aortic atherosclerosis, (2) the degree and type of vascular calcification, and (3) factors involved in the calcification process. For creating CRF, 8-wk-old apolipoprotein E gene knockout (apoE(-/-)) mice underwent partial kidney ablation. Control animals underwent sham operation. Aortic atherosclerotic plaques and calcification were evaluated using quantitative morphologic image processing. At 6 wk after nephrectomy, CRF mice had significantly higher serum urea, cholesterol, and triglyceride concentrations than non-CRF controls. The serum levels of advanced oxidation protein products were elevated in the uremic group and were correlated with serum urea levels. Atherosclerotic lesions in thoracic aorta were significantly larger in uremic apoE(-/-) mice than in nonuremic controls. The relative proportion of calcified area to total surface area of both atherosclerotic lesions and lesion-free vascular tissue was increased in aortic root of uremic apoE(-/-) mice when compared with controls. The calcium deposits were made of hydroxyapatite and calcite crystals. In addition, plaques from uremic animals showed a significant increase in collagen content, whereas the degree of macrophage infiltration was comparable in both groups. There was no difference in mean arterial BP. These findings demonstrate that CRF aggravates atherosclerosis in apoE(-/-) mice. Moreover, CRF enhances arterial calcification at both atheromatous intimal sites and atheroma-free medial sites. We anticipate that this experimental model will be useful to test treatment strategies aimed at decreasing the accelerated atherosclerosis and arterial calcification in uremia.