tbuckley/cabot-search huggingface dataset:
Effect of Periodontitis on Overt Nephropathy and End-Stage Renal Disease in Type 2 Diabetes
Authors: Wendy A. Shultis, E. Jennifer Weil, Helen C. Looker, Jeffrey M. Curtis, Marc Shlossman, Robert J. Genco, William C. Knowler, Robert G. Nelson
Journal: Diabetes Care (2007)

OBJECTIVE—The purpose of this study was to investigate the effect of periodontitis on development of overt nephropathy, defined as macroalbuminuria, and end-stage renal disease (ESRD) in type 2 diabetes. RESEARCH DESIGN AND METHODS—Individuals residing in the Gila River Indian Community aged ≥25 years with type 2 diabetes, one or more periodontal examination, estimated glomerular filtration rate ≥60 ml/min per 1.73 m2, and no macroalbuminuria (urinary albumin-to-creatinine ratio ≥300 mg/g) were identified. Periodontitis was classified as none/mild, moderate, severe, or edentulous using number of teeth and alveolar bone score. Subjects were followed to development of macroalbuminuria or ESRD, defined as onset of renal replacement therapy or death attributed to diabetic nephropathy. RESULTS—Of the 529 individuals, 107 (20%) had none/mild periodontitis, 200 (38%) had moderate periodontitis, 117 (22%) had severe periodontitis, and 105 (20%) were edentulous at baseline. During follow-up of up to 22 years, 193 individuals developed macroalbuminuria and 68 developed ESRD. Age- and sex-adjusted incidence of macroalbuminuria and ESRD increased with severity of periodontitis. After adjustment for age, sex, diabetes duration, BMI, and smoking in a proportional hazards model, the incidences of macroalbuminuria were 2.0, 2.1, and 2.6 times as high in individuals with moderate or severe periodontitis or those who were edentulous, respectively, compared with those with none/mild periodontitis (P = 0.01). Incidences of ESRD in individuals with moderate or severe periodontitis or in those who were edentulous were 2.3, 3.5, and 4.9 times as high, respectively, compared with those with none/mild periodontitis (P = 0.02). CONCLUSIONS—Periodontitis predicts development of overt nephropathy and ESRD in individuals with type 2 diabetes. Whether treatment of periodontitis will reduce the risk of diabetic kidney disease remains to be determined.
Myocardial anaerobic metabolism occurs at a critical coronary venous PO2 in pigs.
Authors: K R Walley, R M Collins, D J Cooper, C B Warriner
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We tested the hypothesis that the onset of myocardial anaerobic metabolism is fundamentally different from the whole body and other organs, where the onset of anaerobic metabolism occurs at a critical oxygen extraction ratio--not at a critical venous PO2. We measured oxygen saturation and PO2 of arterial and coronary venous blood at the onset of global myocardial anaerobic metabolism during progressive hypoxic hypoxia (n = 7) compared with carbon monoxide hypoxia (n = 7), which left-shifted the oxygen-hemoglobin dissociation curve. The onset of global myocardial anaerobic metabolism was defined by decreased myocardial lactate consumption and left ventricular contractility. Coronary venous PO2 was no different during hypoxic hypoxia and carbon monoxide hypoxia at equivalent arterial oxygen saturations, particularly at the onset of myocardial anaerobic metabolism (PO2 17.0 +/- 1.7 torr versus 15.9 +/- 2.2 torr, p = NS). However, the myocardial oxygen extraction ratio was significantly greater during hypoxic hypoxia than during carbon monoxide hypoxia at the onset of myocardial anaerobic metabolism (0.88 +/- 0.02 versus 0.65 +/- 0.04, p < 0.01). Thus, in contrast to the whole body where the onset of anaerobic metabolism occurs at a critical oxygen extraction ratio, the onset of myocardial anaerobic metabolism occurs at a critical coronary venous PO2.
Survival of patients with diabetes and multivessel coronary artery disease after surgical or percutaneous coronary revascularization: results of a large regional prospective study
Authors: Nathaniel W Niles, Paul D McGrath, David Malenka, Hebe Quinton, David Wennberg, Samuel J Shubrooks, Joan F Tryzelaar, Robert Clough, Michael J Hearne, Felix Hernandez, Matthew W Watkins, Gerald T O’Connor
Journal: Journal of the American College of Cardiology (2001)
Case of Dislocation of the Patella on its Edge
Authors: W. F. M. Jackson
Journal: BMJ (1873)

history shows that the child appeared tolerably well, circulation and respiration being perfectly established and efficiently carried on for twenty-seven hours, and that he lived for fifty-four hours.Descriptionz of I/ie Heart.-Theheart, which was normal in size, weight, and situation, consisted of two auricles and but one ventricle, from which a single artery arose, giving off, first of all, two pulmonary arteries, and then, pursuing its course in the ordinary direction of the aorta, gave origin to the usual number of aortic branches.The single emergent vessel, which was both pulmonary artery and aorta in one, was larger than either vessel at birth taken singly, and arose from the right and anterior border of the ventricle.It was furnished with three well formed semilunar valves, and gave origin to the two pulmonary arteries, half an inch after leaving the heart: the pulmonary arteries were situated close together, the left, however, being at a slightly higher level than the right.The right auricle was larger than usual, the left extremely small; the foramen ovale was large and patent ; the right auricle received the caval, and the left the pulmonary veins, in the ordinary manner.There was no trace of a ventricular septum, but the left wall of the single ventricle was double the thickness of the right.The auriculo-ventricular valve communicated with the right auricle alone ; it -was neither clearly bicuspid or tricuspid, but approximated the mitral valve in character rather than the other.
Precision of glomerular filtration rate determinations for long-term slope calculations is improved by simultaneous infusion of 125I-iothalamate and 131I-hippuran.
Authors: A J Apperloo, D de Zeeuw, A J Donker, P E de Jong
Journal: Journal of the American Society of Nephrology (1996)

In studies on the progression of chronic renal failure the measurement of GFR must be very reliable. Sequential determination of GFR using the renal clearances of exogenous tracers such as inulin or iothalamate is the most accepted method. However, because of inaccuracies in urine collection, intratest variation, and thus intertest variation, of these clearances is considerable. This has a negative impact on the precision of long-term slope estimations. A previously described method of GFR determination on the basis of simultaneous infusion of 131I-hippuran and 125I-iothalamate corrects for inaccurate urine collection. To study whether this correction method improves the precision of the GFR slope measurement, this study analyzed longitudinal GFR data obtained in 71 patients with renal disease during a follow-up of 84 to 180 wk (477 renal function studies). All GFR were calculated by using both the standard renal clearance method and the correction method. The intratest and intertest coefficient of variation was significantly smaller for the correction method compared with the standard method (1.93 +/- 0.20 versus 8.48 +/- 1.66% P < 0.0005; and 2.88 +/- 0.32 versus 5.12 +/- 0.66%, P < 0.005, respectively). As a result, the precision of the GFR slope estimation was significantly better with the correction method compared with the standard method (error of the slope, 1.63 +/- 1.09 versus 2.35 +/- 2.36 mL/min per yr, P < 0.01). This improvement in precision of the slope by using the correction method reduces the necessary sample size needed to detect a GFR slope difference between interventions to about 30% of that needed when using the standard method. It is concluded that the precision of GFR measurements is improved by using correction for inaccurate urine collection with concomitant 131I-hippuran clearance.
c-Myc and eIF4F Are Components of a Feedforward Loop that Links Transcription and Translation
Authors: Chen-Ju Lin, Regina Cencic, John R. Mills, Francis Robert, Jerry Pelletier
Journal: Cancer Research (2008)

Abstract The Myc/Max/Mad family of transcription factors and the eukaryotic initiation factor 4F (eIF4F) complex play fundamental roles in regulating cell growth, proliferation, differentiation, and oncogenic transformation. eIF4F is involved in the recruitment of ribosomes to mRNAs and is thought to generally be the rate-limiting phase of translation. Here, we show that c-Myc directly activates transcription of the three subunits of eIF4F (eIF4E, eIF4AI, and eIF4GI). These transcriptional effects are mediated through canonical E-boxes (5′CACGTG3′) present in the promoters of these genes. In addition, the c-Myc antagonist Mad1 down-regulates the expression of eIF4F subunits. We also show that MycER activation stimulates protein synthesis at the level of translation initiation. Increased eIF4F levels result in stimulation of c-Myc mRNA translation specifically, as assessed by quantitative reverse transcription–PCR. We use a murine model of lymphomagenesis to show the expression of eIF4F subunits is also up-regulated by c-Myc in vivo. Our results suggest the presence of a feedforward loop involving c-Myc and eIF4F that serves to link transcription and translation and that could contribute to the effects of c-Myc on cell proliferation and neoplastic growth. [Cancer Res 2008;68(13):5326–34]
Changing gears: bicycling as the panacea for physical inactivity?
Authors: Adrian Bauman, Sylvia Titze, Chris Rissel, Pekka Oja
Journal: British Journal of Sports Medicine (2011)

Etoposide [4′-demethylepipodophyllotoxin-9-(4,6-O-ethylidene)-β-D-glucopyranoside] is a substrate for P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A. This study was designed to investigate the effects of quercetin (3,5,7,3′,4′-pentahydroxyflavanone), a P-gp and CYP3A inhibitor, on the pharmacokinetics of etoposide in rats. Etoposide was administered to rats orally (9 mg/kg) or i.v. (3 mg/kg) without or with quercetin (1, 5 or 15 mg/kg). The plasma concentration of etoposide was determined by high performance liquid chromatography (HPLC) equipped with a fluorescence detector. In the presence of quercetin, the pharmacokinetic parameters of etoposide were significantly altered in the oral group, but not in the i.v. group. The presence of quercetin significantly (5 mg/kg, p&lt;0.05; 15 mg/kg, p&lt;0.01) increased the area under the plasma concentration-time curve (AUC) of orally administered etoposide from 43.0 or 53.2% . The presence of 5 or 15 mg/kg of quercetin significantly (p&lt;0.05) decreased the total body clearance (CL/F) of oral etoposide. Consequently, compared to the control group (8.87%), the presence of quercetin significantly (5 mg/kg, p&lt;0.05; 15 mg/kg, p&lt;0.01) increased the absolute bioavailability (AB) of etoposide to 12.7 or 13.6% . The enhanced oral bioavailability of etoposide by quercetin could mainly be due to inhibition of P-gp-mediated efflux and CYP3A-catalyzed metabolism in the intestine by quercetin. The dosage regimen of etoposide in cancer therapy should take drug interaction into consideration when etoposide is administered with quercetin or dietary supplements containing quercetin.
Ductus arteriosus sling: report of a newly recognised anomaly and its surgical correction.
Authors: J P Binet, J F Conso, J Losay, P Narcy, E J Raynaud, F Beaufils, C Dor, J Bruniaux
Journal: Thorax (1978)

Surgical exploration of a 7-week-old infant with a diagnosis of 9pulmonary artery sling9 (left pulmonary artery arising from the right) revealed the true nature of the abnormality to be persistence of the ductus arteriosus which connected the right pulmonary artery to the aortic isthmus. This malformation has not been described previously. It has the same symptomatology as 9pulmonary artery sling9 and it may be treated by surgical ligation and division. We suggest the term 9ductus arteriosus sling9 to describe this rare congenital anomaly.
The Role of GC-Biased Gene Conversion in Shaping the Fastest Evolving Regions of the Human Genome
Authors: D. Kostka, M. J. Hubisz, A. Siepel, K. S. Pollard
Journal: Molecular Biology and Evolution (2011)

GC-biased gene conversion (gBGC) is a recombination-associated evolutionary process that accelerates the fixation of guanine or cytosine alleles, regardless of their effects on fitness. gBGC can increase the overall rate of substitutions, a hallmark of positive selection. Many fast-evolving genes and noncoding sequences in the human genome have GC-biased substitution patterns, suggesting that gBGC-in contrast to adaptive processes-may have driven the human changes in these sequences. To investigate this hypothesis, we developed a substitution model for DNA sequence evolution that quantifies the nonlinear interacting effects of selection and gBGC on substitution rates and patterns. Based on this model, we used a series of lineage-specific likelihood ratio tests to evaluate sequence alignments for evidence of changes in mode of selection, action of gBGC, or both. With a false positive rate of less than 5% for individual tests, we found that the majority (76%) of previously identified human accelerated regions are best explained without gBGC, whereas a substantial minority (19%) are best explained by the action of gBGC alone. Further, more than half (55%) have substitution rates that significantly exceed local estimates of the neutral rate, suggesting that these regions may have been shaped by positive selection rather than by relaxation of constraint. By distinguishing the effects of gBGC, relaxation of constraint, and positive selection we provide an integrated analysis of the evolutionary forces that shaped the fastest evolving regions of the human genome, which facilitates the design of targeted functional studies of adaptation in humans.
The role of mathematics in heuristic performance
Authors: Paul C. Kainen
Journal: Behavioral and Brain Sciences (2000)

A mathematical approach to heuristics is proposed, in contrast to Gigerenzer et al.'s assertion that laws of logic and probability are of little importance. Examples are given of effective heuristics in abstract settings. Other short-comings of the text are discussed, including omissions in psychophysics and cognitive science. However, the authors' ecological view is endorsed.
The need for standardisation of peak flow charts
Authors: H K Reddel
Journal: Thorax (2005)

Peak expiratory flow (PEF) monitoring is recommended in asthma guidelines as a tool for assessing severity, monitoring response to treatment, detecting exacerbations, identifying triggers, and providing objective justification for treatment to the patient, but some clinicians have expressed concerns about its relevance in the management of asthma. We have identified a sevenfold variation in the scale of existing PEF charts, with resulting wide variation in the appearance of the same PEF date on different charts. There is an obvious need for standardisation of PEF charts to avoid confusion for patients and to allow development of pattern recognition skills by clinicians. Evidence is provided from visual perception studies to suggest that preference should be given to a horizontally compressed PEF chart to facilitate identification of exacerbations and of overall trends, but this needs to be formally evaluated by retrospective and prospective studies. It is hoped that clinical expertise in PEF pattern recognition can eventually be incorporated into electronic decision making algorithms, as has occurred in occupational asthma, but, in the meantime, the ideal PEF chart for asthma management will represent a compromise between ease of manual data entry and ease of interpretation.
CTLA-4 Blockade with Ipilimumab: Long-term Follow-up of 177 Patients with Metastatic Melanoma
Authors: Peter A. Prieto, James C. Yang, Richard M. Sherry, Marybeth S. Hughes, Udai S. Kammula, Donald E. White, Catherine L. Levy, Steven A. Rosenberg, Giao Q. Phan
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Treatment with ipilimumab can cause objective tumor responses in patients with metastatic melanoma. We have treated 177 evaluable patients in three clinical trials and have long-term follow-up to evaluate the durability of responses. Experimental Design: Patients with metastatic melanoma were treated in three trials from 2002 to 2005. In protocol 1, 56 patients received ipilimumab with gp100 peptides. In protocol 2, 36 patients received ipilimumab with interleukin-2. In protocol 3, 85 patients received ipilimumab with intrapatient dose-escalation and were randomized to receive gp100 peptides. We have analyzed their long-term follow-up and survival data. Results: With median follow-up for protocols 1, 2, and 3 being 92, 84, and 71 months, median survival was 14, 16, and 13 months with 5-year survival rates being 13%, 25%, and 23%, respectively. Patients in protocol 2 had a 17% complete response (CR) rate, compared with 7% in protocol 1 and 6% in protocol 3. These CR rates are higher than previously reported for the same trials because some patients who eventually became complete responders had continual tumor regression months to years after therapy. All but one of the 15 complete responders are ongoing at 54+ to 99+ months. Conclusions: This report provides the longest follow-up of patients with melanoma treated with ipilimumab and shows that ipilimumab can induce durable, potentially curative tumor regression in a small percentage of patients with metastatic melanoma. The combination of ipilimumab and interleukin-2 seems to have an increased CR rate, but this needs to be tested in a randomized trial. Clin Cancer Res; 18(7); 2039–47. ©2012 AACR.
ATP Depletion Of Tubular Cells Causes Dissociation of the Zonula Adherens and Nuclear Translocation of β-Catenin and LEF-1
Authors: Valerie R. Price, Christine A. Reed, Wilfred Lieberthal, John H. Schwartz
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. This study examined the events associated with the reversible disruption of the structural and functional integrity of the zonula occludens (ZA) induced by ATP depletion of renal tubular cells. It shows that loss of the ZA after ATP depletion is associated with the withdrawal of E-cadherin, α-catenin, and β-catenin, probably as intact cadherin-catenin complexes from the basolateral membrane of tubular cells. The relative amounts of all three proteins increased in the Triton X-100–insoluble fraction of cell lysates and decreased in the Triton X-100–soluble pool. These changes were reversed with repletion of cell ATP. It is additionally shown that ATP depletion induces nuclear translocation of β-catenin and T cell factor (TCF)/lymphoid enhancer factor–1 (LEF-1), a transcriptional factor with which β-catenin associates. The redistribution of the ZA proteins as intact E-cadherin-catenin complexes from the plasma membrane facilitates the rapid recovery of the ZA after sublethal ischemic injury. The translocation of β-catenin and TCF/LEF-1 to the nucleus indicates that ATP depletion may activate the wnt/wingless signal transduction pathway. Thus, entirely novel evidence is provided that both of the known roles of β-catenin, as a structural part of the ZA and as a component of the wnt/wingless pathway, play a role after sublethal ischemic injury to tubular cells. It is also speculated that the nuclear translocation of β-catenin and TCF/LEF-1 modulates gene expression after ischemic injury and may contribute to events necessary for renal regeneration and repair after ischemic injury.
Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial
Authors: Rajendra Badwe, Rohini Hawaldar, Nita Nair, Rucha Kaushik, Vani Parmar, Shabina Siddique, Ashwini Budrukkar, Indraneel Mittra, Sudeep Gupta
Journal: The Lancet Oncology (2015)
Nonneoplastic lesions of the ovary in Fischer 344 rats and B6C3F1 mice.
Authors: C A Montgomery, R H Alison
Journal: Environmental Health Perspectives (1987)

The National Toxicology Program's pathology database on 2-year carcinogenicity studies was reviewed for nonneoplastic ovarian disease. Ovaries from 39,941 female Fischer rats and 41,444 female B6C3F1 mice were examined. A variety of inflammatory, degenerative, vascular, and proliferative lesions were documented and are described. The most common ovarian lesions in rats were cysts (6%). The most frequent ovarian lesions in mice were cysts (15%), acute inflammation (4%), degeneration (4%), vascular disease (2.5%), and atrophy (2%). There was no difference in incidence of ovarian disease between controls and treated animals. The frequency of ovarian disease in mice exceeded the frequency in rats in every category.
Dclk1 distinguishes between tumor and normal stem cells in the intestine
Authors: Yuki Nakanishi, Hiroshi Seno, Ayumi Fukuoka, Taro Ueo, Yuichi Yamaga, Takahisa Maruno, Naoko Nakanishi, Keitaro Kanda, Hideyuki Komekado, Mayumi Kawada, Akihiro Isomura, Kenji Kawada, Yoshiharu Sakai, Motoko Yanagita, Ryoichiro Kageyama, Yoshiya Kawaguchi, Makoto M Taketo, Shin Yonehara, Tsutomu Chiba
Journal: Nature Genetics (2012)
Memory T Cell Subsets, Migration Patterns, and Tissue Residence
Authors: Scott N. Mueller, Thomas Gebhardt, Francis R. Carbone, William R. Heath
Journal: Annual Review of Immunology (2012)

Tissues such as the skin and mucosae are frequently exposed to microbial pathogens. Infectious agents must be quickly and efficiently controlled by our immune system, but the low frequency of naive T cells specific for any one pathogen means dependence on primary responses initiated in draining lymph nodes, often allowing time for serious infection to develop. These responses imprint effectors with the capacity to home to infected tissues; this process, combined with inflammatory signals, ensures the effective targeting of primary immunity. Upon vaccination or previous pathogen exposure, increased pathogen-specific T cell numbers together with altered migratory patterns of memory T cells can greatly improve immune efficacy, ensuring infections are prevented or at least remain subclinical. Until recently, memory T cell populations were considered to comprise central memory T cells (TCM), which are restricted to the secondary lymphoid tissues and blood, and effector memory T cells (TEM), which broadly migrate between peripheral tissues, the blood, and the spleen. Here we review evidence for these two memory populations, highlight a relatively new player, the tissue-resident memory T cell (TRM), and emphasize the potential differences between the migratory patterns of CD4(+) and CD8(+) T cells. This new understanding raises important considerations for vaccine design and for the measurement of immune parameters critical to the control of infectious disease, autoimmunity, and cancer.
The Emperor of Ice-Cream
Authors: D. O'Neill
Journal: BMJ (2012)

Although death is a constant companion of medical practice, we are rarely well equipped for the juxtaposition of life and the living with death and the dying. From the chatter from the nurses’ station and the hubbub of visiting families to the quiet of the side room, there is a constant and often uneasy sense of two parallel worlds jostling with each other.

The respectful stillness and calm in the company of the dying eventually segues into discussion and even laughter, with episodic, sometimes embarrassed, lapses back into solemnity and silence. An awareness of the awesome nature of what we are witnessing is constantly …