tbuckley/cabot-search huggingface dataset:
Rat renal arcade segment expresses vasopressin-regulated water channel and vasopressin V2 receptor.
Authors: B K Kishore, B Mandon, N B Oza, S R DiGiovanni, R A Coleman, N L Ostrowski, J B Wade, M A Knepper
Journal: Journal of Clinical Investigation (1996)

The arcades are long, branched renal tubules which connect deep and mid-cortical nephrons to cortical collecting ducts in the renal cortex. Because they are inaccessible by standard physiological techniques, their functions are poorly understood. In this paper, we demonstrate that the arcades are a site of expression of two proteins, aquaporin-2 (the vasopressin-regulated water channel) and the V2 vasopressin receptor, that are important to regulated water transport in the kidney. Using a peptide-derived polyclonal antibody to aquaporin-2, quantitative ELISA in microdissected segments showed that aquaporin-2 is highly expressed in arcades and that the expression is increased in response to restriction of fluid intake. Immunocytochemistry revealed abundant aquaporin-2 labeling of structures in the cortical labyrinth in a pattern similar to that of the Na(+)-Ca2+ exchanger and kallikrein, marker proteins expressed in arcades but not in cortical collecting ducts. RT-PCR experiments demonstrated substantial aquaporin-2 and V2 receptor mRNA in microdissected arcades. In situ hybridization, using 35S-labeled antisense cRNA probes for the V2 receptor demonstrated strong labeling of both arcades and cortical collecting ducts. Thus, these results indicate that the arcades contain the specific proteins associated with vasopressin-regulated water transport, and may be a heretofore unrecognized site of free water absorption.
926. Recombinant AAV Vectors Pseudotyped with Serotype-1 Capsid Mediates Early Onset of Gene Expression in Mouse Hearts
Authors: Hua Su, Yu Huang, Alicia Barcena, Janice Arakawa-Hoyt, Jianqin Ye, William Grossman, Yuet W. Kan
Journal: Molecular Therapy (2005)

Top of pageAbstract
Adeno-associated virus serotype 2 (AAV2) has been used most frequently as vector in experiments on cardiac gene therapy. We have used this vector to deliver vascular endothelial growth factor (VEGF) gene controlled by the hypoxia response element (HRE) and a cardiac myosin light chain 2v promoter. We achieved cardiac-specific and hypoxia-responsive gene expression that induced neovascular formation in ischemic murine hearts and improved cardiac function. However, gene expression mediated by AAV2 vector in hearts was delayed and did not reach the maximum level until about 4 weeks after intramyocardial injection. Irreversible myocardial injury could have occurred during this period of delay. Because hypoxia inducible factor 1 (HIF-1) is induced immediately at the onset of hypoxia, earlier onset of the HRE regulated gene expression should be more effective in inducing therapeutic angiogenesis. Recently, studies on AAV with different serotypes have shown that they differ in their transduction efficiency with different tissues. To identify a serotype that can efficiently mediate early expression of transgene in the myocardium, we packaged into serotypes 1 to 5 capsids, AAV vector carrying CMV promoter driving the mouse erythropoietin (Epo) gene. The packaged vectors were injected into murine hearts intramyocardially. Gene expression was studied by real-time RT-PCR. The kinetics of Epo expression was studied by measuring the hematocrit after AAVEpo gene transduction at different time points. We found that AAV1, 4 and 5 mediated earlier and higher gene expression than AAV2. Gene expression mediated by AAV1 increased faster than AAV4 and 5, and became the highest after day 4. To compare the early gene expression mediated by AAV serotype 1 and 2, we packaged into these capsids AAV-LacZ vectors that carried a CMV promoter driving LacZ gene expression and injected them to normal and ischemic hearts. Gene expression was detected by LacZ staining. The LacZ expression was detected in the normal and ischemic myocardium one day after AAV1-LacZ injection, while no LacZ expression could be detected in the hearts injected with AAV2-LacZ at this time. At day 14, 100% of the cardiomyocytes around needle injection sites were infected by AAV1-LacZ vector, whereas only sporadic cardiomyocytes were infected by AAV2-LacZ. These results indicate that AAV1 can mediate gene expression within one day. HRE regulated VEGF gene packaged in this capsid will induce very early gene expression and therefore enhance the therapeutic effect.
Solitary Pulmonary Nodules
Authors: Kenneth M. Moser
Journal: JAMA (1974)

The discovery of a solitary pulmonary nodule has long presented physician and patient with a difficult decision. The article by Nathan in this issue ofThe Journalmakes it appear as if the decision were an easy one. This conversion from complexity to simplicity is, unfortunately, more illusion than reality. It is accomplished not with mirrors but with statistics plus one major omission: the contribution of the individual patient to the decision-making matrix. Alas, in the real world, there are only patients, not statistics, or, put another way, one must stop at the bedside on the path between the library and the ultimate decision. There are three basic facts about the patient with a solitary pulmonary nodule, on which everyone can agree: (1) a substantial percentage of these patients have benign nodules, (2) five-year survival rates among patients with resection of malignant nodules are substantially higher than in other bronchogenic
Prospective Exploratory Analysis of the Association Between Tumor Response, Quality of Life, and Expenditures Among Patients Receiving Paclitaxel Monotherapy for Refractory Metastatic Breast Cancer
Authors: Shanu Modi, Katherine S. Panageas, Elaine T. Duck, Ariadne Bach, Nancy Weinstock, James Dougherty, Laura Cramer, Clifford Hudis, Larry Norton, Andrew Seidman
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To prospectively evaluate the association between tumor response, change in quality of life (QoL), and hospital expenditures in patients with metastatic breast cancer (MBC) receiving single-agent paclitaxel. PATIENTS AND METHODS: Eligible patients had bidimensionally measurable MBC and any number of previous therapies, excluding taxane chemotherapy. Paclitaxel was administered by various different infusion schedules. QoL measures were evaluated for each patient at baseline and serially using the Memorial Symptom Assessment Scale (MSAS)-Global Distress Index (GDI) and Functional Assessment of Cancer Therapy–Breast (FACT-B) instruments. Patients were assessed for early (first 6 weeks) and ever changes in QoL parameters. Charges were monitored through the hospital’s centralized computer billing system and converted to cost ratios for the analysis. Correlations between response and improvement in QoL were assessed by Fisher’s exact test statistic. Associations between improvements in QoL with cost ratios were assessed by logistic regression and likewise between response and cost ratios. RESULTS: Of the 59 patients treated, 50 had sufficient data for comparative analyses. The overall response rate was 24% (all partial responses). Minor responses were observed in 17% of patients, 25% had stable disease, and 29% had progression. Responding patients had significant improvement in QoL as assessed by MSAS-GDI (P = .004) and FACT-B (P = .028). The mean total cost/month ratios for patients experiencing improved GDI QoL scores was 1.31 versus 1.56 for those without QoL benefit (P = .52) and 1.05 versus 1.76 for responders versus nonresponders, respectively (P = .07). CONCLUSION: Patients with evidence of tumor response on paclitaxel had a QoL benefit not observed in nonresponders, and this response was associated with a trend for lower overall costs.
Geriatric depression scale can be used in older people in primary care
Authors: C. L E Katona, P. M Katona
Journal: BMJ (1997)

The real ethics of rationing Purchasers, not surgeons, control waiting listsEditor-I applaud the BMJ's efforts to bring the important issue of rationing to the fore, but I cannot allow one aspect of Light's contribution to go without challenge. 1Under the heading "parasitic privatisation" he says, "to top it off, the surgeons control the waiting lists" (to encourage patients into the private sector).I despair that someone of his academic stature should show such a lack of understanding of the purchaser-provider split that we have had in the NHS for the past six years.In the vast majority of cases we as surgeons have a contract with purchasers that places an upper limit on the number of patients on whom we can operate.Thus surgeons have no control over the number of patients having surgery and therefore, by definition, over the waiting list.The role of the surgeon is to prioritise, on clinical grounds, within the contracted number.If surgeons are to operate on more patients then purchasers must contract for more operations.The onus to reduce waiting time, and therefore encourage patients not to use the private sector, lies solely with the purchasers.
Effects of exercise on lung lymph flow in sheep and goats during normoxia and hypoxia.
Authors: G Coates, H O'Brodovich, A L Jefferies, G W Gray
Journal: Journal of Clinical Investigation (1984)

Vigorous exercise causes a marked increase in cardiac output with only a minimal increase in measureable pulmonary vascular pressures. These changes in pulmonary hemodynamics should affect lung water and solute movement. On nine occasions, we measured the effect of normoxic exercise on lung lymph flow in four sheep and two goats with chronic lymph fistulas (wt = 15-25 kg). In addition, lymph flow was also measured on five occasions in sheep during exercise at reduced barometric pressures (430 and 380 mmHg). During normobaria, the animals ran at 3-5 km/h with 0-10% elevation of the treadmill for 15 to 85 min. Exercise on average caused a 100% increase in cardiac output, a 140% increase in lung lymph flow, and a slight but significant reduction in lymph to plasma concentration ratio (l/p) for total protein and albumin (mol wt = 70,000). There was a significant linear correlation between lymph flow and cardiac output (r = 0.87, P less than 0.01). There was no change in l/p for IgG (mol wt = 150,000) or IgM (mol wt = 900,000) and no significant change in mean pulmonary arterial (Ppa) or mean left atrial (Pla) pressures. Transition from normobaria to hypobaria caused an increase in Ppa but no change in Pla, cardiac output, or lymph flow. Exercise during hypobaria caused increases in lymph flow that were qualitatively similar to changes observed during normobaric exercise: there was a 60% increase in cardiac output, a 90% increase in lymph flow, and an 11% reduction in l/p for total protein. There was no change in l/p for albumin, IgG, or IgM, and no further change in Ppa. The increased lymph flow during normoxic and hypobaric exercise is best explained by an increase in pulmonary vascular surface area for fluid and protein exchange. Our results suggest that the normal ovine lung has the potential to nearly triple the amount of perfused microvascular surface area. This speculation is relevant to the interpretation of lymph flow data from other experiments.
Hepatocyte Necrosis Induced by Oxidative Stress and IL-1α Release Mediate Carcinogen-Induced Compensatory Proliferation and Liver Tumorigenesis
Authors: Toshiharu Sakurai, Guobin He, Atsushi Matsuzawa, Guann-Yi Yu, Shin Maeda, Gary Hardiman, Michael Karin
Journal: Cancer Cell (2008)
The Osteoporotic Syndrome: Detection, Prevention, and Treatment
Authors: Marshall R. Urist
Journal: JAMA (1988)

<h3>Osteoporosis Update 1987, edited by Harry K. Genant, 328 pp, with illus, $79, San Francisco, Radiology Research and Education Foundation (University of California, Room 569-U; 941430958), 1987.</h3> <i>The Osteoporotic Syndrome</i>is a multicontributor work that is small, handy, and well written. It covers everything that is currently being done about osteoporosis in the major medical centers of the world. The last chapter contains a revealing statement: Like AIDS, effective modes of therapy of this public health problem [osteoporosis] are still unavailable. We should plan now to decrease these occurrences of morbidity and mortality in future years by instituting preventative measures early in a woman's life. This comparison, with its public health implications, is interesting when one compares the conditions in other aspects: the etiology of the acquired immunodeficiency syndrome, a lifethreatening viral disease, is known. Osteoporosis is a disease of unknown etiology. A typical case is hardly treated as a
Reduced Awareness of Hypoglycemia in Adults With IDDM: A prospective study of hypoglycemic frequency and associated symptoms
Authors: William L Clarke, Daniel J Cox, Linda A Gonder-Frederick, Diana Julian, David Schlundt, William Polonsky
Journal: Diabetes Care (1995)

OBJECTIVE To prospectively evaluate the frequency and severity of hypoglycemic episodes in IDDM subjects who declare themselves to have reduced awareness of hypoglycemia, to validate their self-designations in their natural environment, and to determine objectively the presence or absence of autonomic and neuroglycopenic symptoms associated with their low blood glucose (BG) levels. RESEARCH DESIGN AND METHODS A total of 78 insulin-dependent diabetes mellitus (IDDM) subjects (mean age 38.3 ± 9.2 years; duration of diabetes 19.3 ± 10.4 years) completed two sets of assessments separated by 6 months. The assessments included reports of frequency and severity of low BG, symptoms associated with low BG, and a BG symptom/estimation trial using a hand-held computer (HHC). Diaries of hypoglycemic episodes were kept for the intervening 6 months. HbA1 levels were determined at each assessment. RESULTS Of the subjects, 39 declared themselves as having reduced awareness of hypoglycemia (reduced-awareness subjects). There were no differences between these reduced-awareness subjects and aware subjects with regard to age, sex, disease duration, insulin dose, or HbA1. During the HHC trials, reduced-awareness subjects were significantly less accurate in detecting BG &amp;lt; 3.9 mmol/l (33.2 ± 47 vs. 47.6 ± 50% detection, P = 0.001) and had significantly fewer autonomic (0.41 ± 0.82 vs. 1.08 ± 1.22, P = 0.006, reduced-awareness vs. aware) and neuroglycopenic (0.44 ± 0.85 vs. 1.18 ± 1.32, P = 0.004, reduced-awareness vs. aware) symptoms per subject. Prospective diary records revealed that reduced-awareness subjects experienced more moderate (351 vs. 238, P = 0.026) and severe (50 vs. 17, P = 0.0062) hypoglycemic events. The second assessment results were similar to the first and verified the reliability of the data. CONCLUSIONS IDDM subjects who believe they have reduced awareness of hypoglycemia are generally correct. They have a history of more moderate and severe hypoglycemia, are less accurate at detecting BG &amp;lt; 3.9 mmol/l, and prospectively experience more moderate and severe hypoglycemia than do aware subjects. Neither disease duration nor level of glucose control explains their reduced awareness of hypoglycemia. Reduced-awareness individuals may benefit from interventions designed to teach them to recognize all of their potential early warning symptoms.
How to do it
Authors: R. G. Richards
Journal: BMJ (2011)

How will the variations highlighted in the NHS Health Atlas of Variation in Healthcare be addressed,1 when little has changed since Glover’s analysis of the variation in tonsillectomy rates in England in 1938?2

Foundation trust contracts should require that unexplained and unacceptable (“bad”) clinical variation be reduced and reported each year to show progress. Commissioners …
570 CLINICAL EVALUATION OF THE ARMS RT-PCR FOR THE QUANTITATIVE DETECTION OF M204V VARIANTS IN CHRONIC HBV PATIENTS
Authors: F. Ntziora, D. Paraskevis, C. Haida, E. Manesis, G. Papatheodoridis, S. Manolakopoulos, E. Hatzitheodorou, S. Chryssou, V. Sypsa, A. Hatzakis
Journal: Journal of Hepatology (2008)
Leucine-Rich Repeat Kinase 2 Regulates the Progression of Neuropathology Induced by Parkinson's-Disease-Related Mutant α-synuclein
Authors: Xian Lin, Loukia Parisiadou, Xing-Long Gu, Lizhen Wang, Hoon Shim, Lixin Sun, Chengsong Xie, Cai-Xia Long, Wan-Jou Yang, Jinhui Ding, Zsu Zsu Chen, Paul E. Gallant, Jung-Hwa Tao-Cheng, Gay Rudow, Juan C. Troncoso, Zhihua Liu, Zheng Li, Huaibin Cai
Journal: Neuron (2009)
Effect of transmural pressure on low density lipoprotein and albumin transport and distribution across the intact arterial wall.
Authors: P A Curmi, L Juan, A Tedgui
Journal: Circulation Research (1990)

To investigate the effect of hyperpressure on the transport of low density lipoprotein (LDL) and albumin in the arterial wall, we measured in vitro the uptake of both iodine-131-labeled LDL and iodine-125-labeled albumin in intact rabbit thoracic aorta, held at in vivo length and pressurized to 70 or 160 mm Hg. Arteries were incubated for 2 hours (n = 8) at 70 mm Hg, and for 5 minutes (n = 4), 30 minutes (n = 4), 1 hour (n = 5), and 2 hours (n = 5) at 160 mm Hg. The transmural distribution of the relative concentrations of LDL (CLDL) and albumin (Calb) across the wall was determined by using a serial frozen sectioning technique. At 70 mm Hg, the mean medial CLDL and Calb values were 0.0018 +/- 0.0007 and 0.0039 +/- 0.0013, respectively. At 160 mm Hg, CLDL and Calb were markedly increased. The distribution of labeled albumin was almost uniform across the media and reached a steady state after 30 minutes, whereas labeled LDL accumulated in the first inner layers, a steady state being achieved after 1 hour. The 1-hour values of CLDL in the first and second luminal sections (0.24 +/- 0.03 and 0.13 +/- 0.05, respectively) were much higher than those of Calb, the CLDL/Calb ratios being 4.12 +/- 0.94 and 2.34 +/- 0.42 (p less than 0.01), respectively. In the subsequent sections, the CLDL decreased markedly and became much lower than the Calb, the CLDL/Calb ratio averaging 0.2 in the two-thirds outer media. To investigate whether LDL was trapped at high pressure in the inner layers, vessels were exposed to a tracer-free intraluminal solution for 30 minutes, after a 30-minute incubation with tracers. After washout, albumin was almost totally removed from the wall, while the CLDL were practically unchanged. Compaction of the media induced by high distending stresses applied to the vessel might have hindered the efflux of LDL, whereas albumin moved freely through the wall. Synergy between increased endothelial permeability and compaction of the media together with enhanced pressure-driven convection might account for the marked increase in LDL concentration observed in the inner wall at high pressure.
Atorvastatin Improves Myocardial Perfusion in a Patient With Hypercholesterolemia and Single-Vessel Coronary Disease
Authors: Mauro Feola, Alberto Biggi, Fabrizio Rolfo, Alberto Papaleo, Stephane Chauvie, Eugenio La Scala, Eugenio Uslenghi
Journal: Clinical Nuclear Medicine (2006)

Lipid-lowering agents may improve the prognosis in patients with coronary artery disease (CAD) or with risk factors for atherosclerosis. A high dose of atorvastatin (80 mg/d) reduced the LDL cholesterol level in stable patients with CAD and was seen to be as effective as coronary angioplasty in reducing the incidence of ischemic events. In patients with acute coronary syndrome, high-dose atorvastatin (80 mg/d) has lowered the incidence of recurrent ischemic events and emergency rehospitalization. We demonstrated that long-term oral low-dose (10 mg/d) administration of atorvastatin improved myocardial uptake of Tc-99m tetrofosmin in a patient with single-vessel coronary artery disease normalizing the plasma level of LDL cholesterol. The normalization of the perfusion pattern was obtained using the same protocol and level of physical stress after 10 months of therapy.
Snakebite: Sociocultural Anthropological Bias
Authors: Arunachalam Kumar
Journal: PLoS Medicine (2006)

Because of the nature of the analysis used in this study [1], no conclusion is possible.There are plenty of examples in the literature demonstrating the "ecological fallacy".Studies such as this have very little utility other than to generate hypotheses.I tend to think that this association is a marker for greater recognition and treatment for depression.However, it's a brave epidemiologist who would draw any conclusions at all from an ecological association such as this where the outcome is relatively rare.
Characteristics of general practices that prescribe appropriately for asthma
Authors: P. Sturdy, J. Naish, F. Pereira, C. Griffiths, S. Dolan, P. Toon, M. Chambers
Journal: BMJ (1995)

the study period.The inflationary influences on prescribing costs discussed in the introduction have been more important than all of the cost control influences (of which fundholding was only one) combined.The effect of marketing pressure from the pharmaceutical industry is probably the most powerful of these influences; it is discernible in this study in the increase in cost per item of drugs for diseases of the central nervous system and for gastrointestinal disorders.No clinical research evidence exists that
Lack of vitamin D raises risk of heart disease and worsens prognosis for some cancers
Authors: Susan Mayor
Journal: BMJ (2008)

Vitamin D deficiency is well known to be associated with osteoporosis, but two studies published this week have shown that lack of the “sunshine vitamin” also increases the risk of heart disease and is linked to poorer prognosis for some cancers.

A follow-up study of 1739 offspring of the original participants in the Framingham heart study, with no cardiovascular disease, showed that those with low concentrations of vitamin D (below 15 ng/ml) had twice the risk of a first cardiovascular event, such as a myocardial infarction, heart failure or stroke, in the five years from baseline than those with higher concentrations ( Circulation doi: 10.1161.circulationaha.107.706127).

After adjusting for the usual cardiovascular risk factors, including high cholesterol concentrations, diabetes, and hypertension, the researchers found that risk of a cardiovascular event remained 62% higher …
Abstract 3065: Interferon consensus sequence-binding protein (ICSBP) regulates the transforming growth factor-beta type I receptor expression in osteosarcoma cells
Authors: Jee Young Sung, Yong-Nyun Kim, Byung-Kiu Park
Journal: Cancer Research (2012)

Abstract Transforming growth factor-beta (TGF-β), known as a tumor suppressor, may exert tumor promoting activity in the advanced stage of cancer. Previously, we reported that interferon consensus sequence-binding protein (ICSBP), also known as interferon regulatory factor-8, up-regulates TGF-βtype I receptor (TGF-βR I), and augments growth in HL-60 leukemic cells. In the current study, we demonstrate that ICSBP expression up-regulates TGF-βR I and increase in cell growth in U2OS human osteosarcoma cells. To further investigate the mechanism of TGF-βR I up-regulation by ICSBP, we tested the possibility that ICSBP regulates promoter activity of TGF-βR I gene. We analyzed the promoter region of the human TGF-βR I gene in U2OS cells to find putative transcription elements regulated by ICSBP. Luciferase reporter gene assays indicated that ICSBP expression could enhance TGF-βR I gene expression, and by promoter deletion analysis we identified a functional ICSBP-dependent region located at nucleotides −300 to −1 in the TGF-βR I promoter. We also performed chromatin immunoprecipitation using anti-ICSBP and found that there are putative ICSBP binding sites in −300 to −1 region. In conclusion, ICSBP increased TGF-βR I expression by binding to TGF-βR I promoter (−300/−1) in U2OS cells. Exploration for the specific ICSBP binding sequences within TGF-βR I promoter (−300/−1) is under way, which may be helpful in understanding the regulatory mechanism involved in TGF-βR I expression by ICSBP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3065. doi:1538-7445.AM2012-3065