tbuckley/cabot-search huggingface dataset:
Sphingosylphosphorylcholine Is a Novel Messenger for Rho-Kinase–Mediated Ca <sup>2+</sup> Sensitization in the Bovine Cerebral Artery
Authors: Satoshi Shirao, Shiro Kashiwagi, Masafumi Sato, Saori Miwa, Fumiaki Nakao, Tetsu Kurokawa, Natsuko Todoroki-Ikeda, Kimiko Mogami, Yoichi Mizukami, Shinichi Kuriyama, Kyousuke Haze, Michiyasu Suzuki, Sei Kobayashi
Journal: Circulation Research (2002)

Although recent investigations have suggested that a Rho-kinase-mediated Ca2+ sensitization of vascular smooth muscle contraction plays a critical role in the pathogenesis of cerebral and coronary vasospasm, the upstream of this signal transduction has not been elucidated. In addition, the involvement of protein kinase C (PKC) may also be related to cerebral vasospasm. We recently reported that sphingosylphosphorylcholine (SPC), a sphingolipid, induces Rho-kinase-mediated Ca2+ sensitization in pig coronary arteries. The purpose of this present study was to examine the possible mediation of SPC in Ca2+ sensitization of the bovine middle cerebral artery (MCA) and the relation to signal transduction pathways mediated by Rho-kinase and PKC. In intact MCA, SPC induced a concentration-dependent (EC50=3.0 micromol/L) contraction, without [Ca2+]i elevation. In membrane-permeabilized MCA, SPC induced Ca2+ sensitization even in the absence of added GTP, which is required for activation of G-proteins coupled to membrane receptors. The SPC-induced Ca2+ sensitization was blocked by a Rho-kinase inhibitor (Y-27632) and a dominant-negative Rho-kinase, but not by a pseudosubstrate peptide for conventional PKC, which abolished the Ca2+-independent contraction induced by phorbol ester. In contrast, phorbol ester-induced Ca2+ sensitization was resistant to a Rho-kinase inhibitor and a dominant-negative Rho-kinase. In primary cultured vascular smooth muscle cells, SPC induced the translocation of cytosolic Rho-kinase to the cell membrane. We propose that SPC is a novel messenger for Rho-kinase-mediated Ca2+ sensitization of cerebral arterial smooth muscle and, therefore, may play a pivotal role in the pathogenesis of abnormal contraction of the cerebral artery such as vasospasm. The SPC/Rho-kinase pathway functions independently of the PKC pathway.
Systems biology for hepatologists
Authors: José M. Mato, Luz M. Martínez-Chantar, Shelly C. Lu
Journal: Hepatology (2014)

Medicine is expected to benefit from combining usual cellular and molecular studies with high-throughput methods (genomics, transcriptomics, proteomics, and metabolomics). These methods, collectively known as omics, permit the determination of thousands of molecules (variations within genes, RNAs, proteins, metabolites) within a tissue, cell, or biological fluid. The use of these methods is very demanding in terms of the design of the study, acquisition, storage, analysis, and interpretation of the data. When carried out properly, these studies can reveal new etiological pathways, help to identify patients at risk for disease, and predict the response to specific treatments. Here we review these omics methods and mention several applications in hepatology research. (Hepatology 2014;60:736–743)
Genetic Prediction of Future Type 2 Diabetes
Authors: Valeriya Lyssenko, Peter Almgren, Dragi Anevski, Marju Orho-Melander, Marketa Sjögren, Carola Saloranta, Tiinamaija Tuomi, Leif Groop
Journal: PLoS Medicine (2005)

Background Type 2 diabetes (T2D) is a multifactorial disease in which environmental triggers interact with genetic variants in the predisposition to the disease. A number of common variants have been associated with T2D but our knowledge of their ability to predict T2D prospectively is limited. Methods and Findings By using a Cox proportional hazard model, common variants in the PPARG (P12A), CAPN10 (SNP43 and 44), KCNJ11 (E23K), UCP2 (−866G>A), and IRS1 (G972R) genes were studied for their ability to predict T2D in 2,293 individuals participating in the Botnia study in Finland. After a median follow-up of 6 y, 132 (6%) persons developed T2D. The hazard ratio for risk of developing T2D was 1.7 (95% confidence interval [CI] 1.1–2.7) for the PPARG PP genotype, 1.5 (95% CI 1.0–2.2) for the CAPN10 SNP44 TT genotype, and 2.6 (95% CI 1.5–4.5) for the combination of PPARG and CAPN10 risk genotypes. In individuals with fasting plasma glucose ≥ 5.6 mmol/l and body mass index ≥ 30 kg/m2, the hazard ratio increased to 21.2 (95% CI 8.7–51.4) for the combination of the PPARG PP and CAPN10 SNP43/44 GG/TT genotypes as compared to those with the low-risk genotypes with normal fasting plasma glucose and body mass index < 30 kg/m2. Conclusion We demonstrate in a large prospective study that variants in the PPARG and CAPN10 genes predict future T2D. Genetic testing might become a future approach to identify individuals at risk of developing T2D.
Use of insulin aspart, a fast-acting insulin analog, as the mealtime insulin in the management of patients with type 1 diabetes.
Authors: P Raskin, R A Guthrie, L Leiter, A Riis, L Jovanovic
Journal: Diabetes Care (2000)

OBJECTIVE: To compare long-term glycemic control and safety of using insulin aspart (IAsp) with that of regular human insulin (HI). RESEARCH DESIGN AND METHODS: This was a multicenter randomized open-label 6-month study (882 subjects) with a 6-month extension period (714 subjects) that enrolled subjects with type 1 diabetes. Subjects administered IAsp immediately before meals or regular HI 30 min before meals; basal NPH insulin was taken as a single bedtime dose in the majority of subjects. Glycemic control was assessed with HbA1c values and 8-point blood glucose profiles at 3-month intervals. RESULTS: Mean postprandial blood glucose levels (mg/dl +/- SEM) were significantly lower for subjects in the IAsp group compared with subjects in the HI group after breakfast (156 +/- 3.4 vs. 185 +/- 4.7), lunch (137 +/- 3.1 vs. 162 +/- 4.1), and dinner (153 +/- 3.1 vs. 168 +/- 4.1), when assessed after 6 months of treatment. Mean HbA1c values (% +/- SEM) were slightly, but significantly, lower for the IAsp group (7.78% +/- 0.03) than for the regular HI group (7.93% +/- 0.05, P = 0.005) at 6 months. Similar postprandial blood glucose and HbA1c values were observed at 12 months. Adverse events and overall hypoglycemic episodes were similar for both treatment groups. CONCLUSIONS: Postprandial glycemic control was significantly better with IAsp compared with HI after 6 and 12 months of treatment. The improvement was not obtained at an increased risk of hypoglycemia. HbA1c was slightly, but significantly, lower for IAsp compared with HI at 6 and 12 months.
Prognostic Significance of Fluorodeoxyglucose Uptake in Non–Small Cell Lung Cancer. A Blurry Picture?
Authors: Wolfgang A. Weber, Johannes Czernin, Michael E. Phelps
Journal: Clinical Cancer Research (2007)

Noninvasive assessment of tumor grading and prediction of patient outcome were among the first applications of positron emission tomography (PET) in oncology ([1][1]). Since then, the relationship between tumor glycolytic activity, as measured by the metabolism of the glucose analogue
Hepatocyte growth factor induces proliferation and morphogenesis in nonparenchymal epithelial liver cells
Authors: Mark Johnson, George Koukoulis, Kunio Matsumoto, Toshikazu Nakamura, Anand Iyer
Journal: Hepatology (1993)

Hepatocyte growth factor is the most potent mitogen known for hepatocytes, and increasing evidence suggests that hepatocyte growth factor plays an important role in liver regeneration. However, hepatocytes are not the only liver epithelial cell population that proliferates during regeneration. Experimental and clinical data indicate that the regenerative liver response also includes the participation of nonparenchymal epithelial cells. The possible role of hepatocyte growth factor in this nonparenchymal epithelial cell regenerative response has not been explored. We studied the effects of hepatocyte growth factor with a model of two normal mouse nonparenchymal epithelial cell-derived cell lines with varying differentiation potentials. Addition of hepatocyte growth factor induced mitogenesis and scattering of colonies growing on culture dishes in both cell lines. Furthermore, hepatocyte growth factor was found to exert a profound morphogenic effect on cells growing in collagen matrixes. Hepatocyte growth factor-treated embryonic BNL CL.2 cell colonies developed elaborately branching elongated cords with only minimal tubularization. Hepatocyte growth factor-treated postnatal NMuLi cell colonies developed a network of anastomosing tubules with wide lumens. These morphological changes were not inhibitable by transforming growth factor-beta and were not induced by other hepatocellular growth factors including epidermal growth factor, transforming growth factor-alpha, acidic fibroblast growth factor and insulin. Histological sections of the hepatocyte growth factor-treated BNL CL.2 cell colonies resembled neocholangioles, believed to include facultative stem cells, which proliferate after submassive and massive hepatic necrosis. Sections of hepatocyte growth factor-treated NMuLi colonies resembled ductules proliferating in biliary tract obstruction from a wide variety of causes. This work represents the first examples of hepatocyte growth factor-induced mitogenesis, scattering and morphogenesis in the same cell lines. More important, our data suggest that hepatocyte growth factor mediates liver response to injury not only by acting on hepatocytes but also by exerting mitogenic and morphogenic influences on nonparenchymal epithelial cell components.
Polymorphic Reentrant Ventricular Tachycardia in the Isolated Rabbit Heart Studied by High-Density Mapping
Authors: Lucas Boersma, Zoltan Zetelaki, Josep Brugada, Maurits Allessie
Journal: Circulation (2002)

The role of dispersion of refractoriness and reentry for the genesis of polymorphic ventricular tachycardia (VT) has recently become emphasized. We investigated the mechanisms of polymorphic arrhythmias in a 2D preparation confining an area of prolonged refractoriness.In 16 Langendorff-perfused rabbit hearts, a sheet of left ventricular epicardium was obtained by a cryoprocedure. Enhanced spatial heterogeneity in a refractory period was created by cooling a central region (diameter=12 mm). This markedly prolonged the refractory period (by 36+/-14 ms) inside but only slightly prolonged it (by 5+/-11 ms) outside the cooled area (n=6). During a control procedure, programmed stimulation with up to 3 premature stimuli induced an episode of monomorphic VT in only 1 of 10 hearts. During regional cooling, episodes of polymorphic VT with a maximum duration of 35 seconds could be induced in all hearts. High-resolution mapping (229 electrodes) of epicardial activation revealed that polymorphic VT was caused by a functional reentrant circuit located partially within the region of prolonged refractoriness. The reentrant wavefront was continuously shifting along the border of the cooled region, resulting in beat-to-beat changes in the excitation pattern. Spontaneous termination of polymorphic VT occurred either by a shift of the reentrant circuit outside the cooled region or by a block in the central common pathway during figure-of-8 reentry in the region of prolonged refractoriness.A shifting functional reentrant circuit was the underlying mechanism of polymorphic VT in a substrate of enhanced spatial heterogeneity of refractoriness.
Brain cancer incidence trends in relation to cellular telephone use in the United States
Authors: P. D. Inskip, R. N. Hoover, S. S. Devesa
Journal: Neuro-Oncology (2010)

The use of cellular telephones has grown explosively during the past two decades, and there are now more than 279 million wireless subscribers in the United States.If cellular phone use causes brain cancer, as some suggest, the potential public health implications could be considerable.One might expect the effects of such a prevalent exposure to be reflected in general population incidence rates, unless the induction period is very long or confined to very long-term users.To address this issue, we examined temporal trends in brain cancer incidence rates in the United States, using data collected by the Surveillance, Epidemiology, and End Results (SEER) Program.Log-linear models were used to estimate the annual percent change in rates among whites.With the exception of the 20 -29-year age group, the trends for 1992 -2006 were downward or flat.Among those aged 20 -29 years, there was a statistically significant increasing trend between 1992 and 2006 among females but not among males.The recent trend in 20 -29-year-old women was driven by a rising incidence of frontal lobe cancers.No increases were apparent for temporal or parietal lobe cancers, or cancers of the cerebellum, which involve the parts of the brain that would be more highly exposed to radiofrequency radiation from cellular phones.Frontal lobe cancer rates also rose among 20 -29-year-old males, but the increase began earlier than among females and before cell phone use was highly prevalent.Overall, these incidence data do not provide support to the view that cellular phone use causes brain cancer.
Early dinner reduces nocturnal gastric acidity.
Authors: P Duroux, P Bauerfeind, C Emde, H R Koelz, A L Blum
Journal: Gut (1989)

This study examines whether eating food at different times has differential effects on intragastric pH. Experiments were done in 23 healthy volunteers (12 men). Intragastric acidity was monitored by ambulatory 22 hour pH-metry. Composition of meals was standardised: breakfast and lunch at 7 am and 12 noon respectively, and dinner at 6 or 9 pm, in random order. The time of going to bed and getting up was also standardised. With early dinner nocturnal pH was higher, than with late dinner (pH median: 1.67 and 1.39, p less than 0.001). During the remaining time periods, pH values were similar. Thus early dinner may be helpful in conditions where low intragastric acidity is desirable.
Effect of propranolol on phosphate reabsorption by superficial nephron segments in response to parathyroid hormone in phosphate-deprived rats.
Authors: A Rybczynska, A Hoppe, F G Knox
Journal: Journal of the American Society of Nephrology (1990)

Phosphate deprivation causes a resistance to the phosphaturic effect of parathyroid hormone. The decreased phosphaturic response to parathyroid hormone in rats fed a low phosphate diet for 1 day can be restored by propranolol infusion. Free-flow micropuncture studies were performed to localize the nephron site of restoration of the phosphaturic effect of parathyroid hormone by propranolol in rats deprived of phosphate for one day. In animals fed low phosphate diet and in the presence of parathyroid hormone, propranolol infusion did not change phosphate delivery to the late proximal tubule; however, fractional delivery of phosphate to the early distal tubule was significantly increased from 18.3 +/- 2.9 to 32.2 +/- 4.1%. In rats fed a normal phosphate diet, propranolol infusion did not change phosphate delivery along the nephron. We conclude that the restoration of the phosphaturic effect of parathyroid hormone by propranolol infusion in rats deprived of phosphate for 1 day is primarily due to decreased reabsorption of phosphate by superficial loop segments, most likely the pars recta segment of the proximal tubule.
Classifying distinct basal cell carcinoma subtype by means of dermatoscopy and reflectance confocal microscopy
Authors: Caterina Longo, Aimilios Lallas, Athanassios Kyrgidis, Harold Rabinovitz, Elvira Moscarella, Silvana Ciardo, Iris Zalaudek, Margaret Oliviero, Amanda Losi, Salvador Gonzalez, Pascale Guitera, Simonetta Piana, Giuseppe Argenziano, Giovanni Pellacani
Journal: Journal of the American Academy of Dermatology (2014)
Erythrocyte‐Inspired Delivery Systems
Authors: Che‐Ming J. Hu, Ronnie H. Fang, Liangfang Zhang
Journal: Advanced Healthcare Materials (2012)

Abstract Herein recent progress in developing red blood cell (RBC)‐inspired delivery systems is reviewed, with an emphasis on how our growing understanding of fundamental biological properties of natural RBCs has been applied in the design and engineering of these delivery systems. Specifically, progress achieved in developing carrier RBCs, a class of delivery vehicles engineered by directly loading natural RBCs with therapeutic agents, will be reviewed. Then alternative approaches to engineering synthetic vehicles through mimicking the mechanobiological and chemico‐biological properties of natural RBCs will be considered. The synthesis and application of RBC membrane‐derived vesicles, of which the natural RBC membranes are collected and directly utilized to prepare drug carriers, will then be discussed. Finally, a recent approach in engineering RBC membrane‐camouflaged nanoparticle systems that combine advantages of natural RBCs and synthetic biomaterials will be highlighted. These developments indicate that RBC‐inspired delivery systems will result in next‐generation nanomedicine with extensive medical applications.
Anti–αv Integrin Monoclonal Antibody Intetumumab Enhances the Efficacy of Radiation Therapy and Reduces Metastasis of Human Cancer Xenografts in Nude Rats
Authors: Shoucheng Ning, Junqiang Tian, Deborah J. Marshall, Susan J. Knox
Journal: Cancer Research (2010)

We previously reported that intetumumab (CNTO 95), a fully human anti-αv integrin monoclonal antibody, is a radiosensitizer in mice with xenograft tumors. Because intetumumab does not cross-react with mouse integrins, but has cross-reactivity with rat integrins, we next studied the potential combined use of radiation therapy and intetumumab in human cancer xenograft models in nude rats to assess effects on both tumor cells and the tumor microenvironment. Nude rats bearing human head and neck cancer and non-small cell lung cancer (NSCLC) xenografts were treated with intetumumab and fractionated local tumor radiotherapy. Effects on tumor growth and metastasis, blood perfusion, oxygenation, and gastrointestinal toxicity were studied. Intetumumab alone had a moderate effect on tumor growth. When combined with fractionated radiation therapy, intetumumab significantly inhibited tumor growth and produced a tumor response rate that was significantly better than with radiation therapy alone. Treatment with intetumumab also significantly reduced lung metastasis in the A549 NSCLC xenograft model. The oxygenation and blood perfusion in xenograft tumors measured by microbubble-enhanced ultrasound imaging were substantially increased after treatment with intetumumab. The combined use of intetumumab and radiation therapy reduced the microvessel density and increased apoptosis in tumor cells and the tumor microenvironment. Toxicity studies showed that treatment with intetumumab did not cause the histopathologic changes in the lungs and did not sensitize the sensitive gastrointestinal epithelium to the effect of radiation therapy. Intetumumab can potentiate the efficacy of fractionated radiation therapy in human cancer xenograft tumors in nude rats without increased toxicity.
Registration as a General Practitioner
Authors: R. Brock
Journal: BMJ (1970)

MEDAL5hconsider such representations at a later date.The profession's negotiators should be well able to ensure that the question of the inclusion of public health doctors is raised without prejudicing what has already been gained in the dispute.It is sophism to argue that public health doctors are not part of the National Health Service, when the 1946 Act itself and the steady development of co-operation and close relations in the working of the Service show otherwise.It is not legalistic views which will determine whether public health doctors are to be included but a sense of fairness, a desire to preserve the community health services on the part of the Government and the local authorities, and, above all, readiness of the medical profession to show unity.The demonstration of unity should be made easier on this occasion by the knowledge that public health doctors have suffered for their willingness not to stand in the way of their colleagues when the Review Body was first set up, that they supported them again in the recent dispute, and that in any case mere self-interest on the part of the profes- sion as a whole requires that no section of it should be left in a position in which it is a source of weakness to the remainder.-Weare, etc.,
The Immune Signature of CD8+CCR7+ T Cells in the Peripheral Circulation Associates with Disease Recurrence in Patients with HNSCC
Authors: Malgorzata Czystowska, William Gooding, Miroslaw J. Szczepanski, Andres Lopez-Abaitero, Robert L. Ferris, Jonas T. Johnson, Theresa L. Whiteside
Journal: Clinical Cancer Research (2012)

Patients with cancer have an increased frequency of circulating apoptosis-sensitive CD8(+)CCR7(neg) T cells and few CD8(+)CCR7(+) T cells versus normal controls. The functional and clinical significance of this imbalance was investigated using peripheral blood of patients with squamous cell carcinoma of the head and neck (HNSCC).The frequency of circulating CD8(+) T cells co-expressing CCR7, CD45RO, CD28, and Annexin V (ANXV) was evaluated in 67 patients and 57 normal controls by flow cytometry. Spearman rank correlations among immunophenotypic profiles were analyzed. Recursive partitioning classified subjects as patients or normal controls based on CD8(+)CCR7(+) T-cell percentages. Kaplan-Meier plots estimated disease-free survival (DFS).The CD8(+)CCR7(+) T-cell frequency was low, whereas that of total CD8(+)CCR7(neg) and ANXV-binding CD8(+)CCR7(neg) T cells was higher in patients with HNSCC than in normal controls (P < 0.001-0.0001). ANXV binding correlated with the absence of CCR7 on CD8(+) T cells (P < 0.001). ANXV binding was negatively correlated with the CD8(+)CD45RO(neg)CCR7(+) (T(N)) cell frequency (P < 0.01) but positively correlated (P < 0.01) with that of CD8(+)CD45RO(+)CCR7(+) (T(CM)) T cells and of the two CCR7(neg) subsets (T(PM) and T(TD)). In recursive partitioning models, the CD8(+)CCR7(+) T-cell frequency of 31% distinguished patients from normal controls with 77% to 88% accuracy after cross-validation. In 25 patients tested before any therapy, the CD8(+)CCR7(+) T-cell frequency of less than 28% predicted disease recurrence within 4 years of definitive therapy (P < 0.0115).The CD8(+)CCR7(+) T-cell frequency in HNSCC patients' blood tested at diagnosis can discriminate them from normal controls and predicts disease recurrence.
Nocturnal Asthma In Latino Children Is Associated With Severe Disease and Allergenic Triggers (GALA II Study)
Authors: Geeta Bhargave, Joy Hsu, Elizabeth Nguyen, Lindsey Roth, Joshua Galanter, Sam Oh, Celeste Eng, Fred Lurmann, Harold J. Farber, Denise Serebrisky, Luisa Borrell, Saunak Sen, William Rodriguez-Cintron, Jose Rodriguez-Santana, Esteban Gonza Burchard, Pedro C. Avila
Journal: Journal of Allergy and Clinical Immunology (2014)