tbuckley/cabot-search huggingface dataset:
Decreased Glucagon Receptors in Diabetic Rat Hepatocytes
Authors: Sam J. Bhathena, Nancy R. Voyles, Stewart Smith, Lillian Recant
Journal: Journal of Clinical Investigation (1978)

The effects of endogenous and exogenous hyperglucagonemia on the specific binding of glucagon to hepatocyte receptors was studied, as was the response of cAMP to glucagon. In streptozotocin diabetic rats, blood glucose and plasma glucagon increased and plasma insulin decreased as compared with controls. Insulin treatment in diabetic rats restored blood glucose and plasma glucagon toward normal and elevated plasma insulin. Specific binding of (125)I-glucagon to isolated hepatocytes (10(6) cells) decreased in diabetic rats (8.17+/-0.38%) compared to controls (14.05+/-0.87%) and was restored by insulin treatment (12.25+/-0.93%). Specific binding of (125)I-insulin in controls was 7.30+/-10.16%; it increased in diabetic rats to 12.50+/-0.86%, and decreased in diabetic rats after insulin treatment (9.08+/-0.87%). Scatchard analysis and the competition plots of the data indicate that decreased glucagon binding and increased insulin binding in diabetes were due to change in the number of receptors rather than a change in their affinity. Hepatocyte cAMP response to glucagon (0.25-5.0 ng/ml) was almost abolished in diabetic rats and was restored with insulin treatment. Specific glucagon binding by hepatocytes from chronically hyperglucagonemic (glucagon injected) rats was decreased (P < 0.005) to 8.76+/-0.61% compared with controls (13.20+/-0.74%) and acutely hyperglucagonemic animals (13.53+/-1.33%). The decreased binding was associated with a 70% decrease in hepatocyte cAMP response to glucagon compared with a normal response in acutely hyperglucagonemic rats.These data appear to support the concept of receptor regulation by ambient hormone level. In both endogenous and exogenous hyperglucagonemia, however, there was a disproportionately large decrease in cAMP response to glucagon compared to the decrease in glucagon binding.
Lactate is an independent marker of severity in hospitalised patients with community-acquired pneumonia
Authors: James D. Chalmers, Aran Singanayagam, Ahsan Akram, Pallavi Mandal, Gourab Choudhury, Maeve Smith, Adam T. Hill
Journal: European Respiratory Journal (2011)

Background: Accurate severity assessment is important to guide initial management of patients with community-acquired pneumonia (CAP). Recognised severity scores may fail to recognise some high risk patients. Lactate is a powerful marker of sepsis but has not been studied in patients with CAP.  Methods: In a prospective study, arterial lactate was measured on admission in 855 patients with CAP. Recognised severity scores were calculated from admission data. The outcomes of interest were 30-day mortality and the need for mechanical ventilation or vasopressor support (MV/VS). The area under the receiver operator characteristic curve (AUC) and multivariable analysis adjusting for pneumonia severity were used to evaluate predictive markers.  Results: 30-day mortality increased with increasing arterial lactate level from 2.8% for lactate ≤2mmol/l, 17.9% for 2.1mmol/l-3.9mmol/l up to 30.8% in patients with lactate ≥ 4mmol/L (p  On multivariate logistic regression, arterial lactate was an independent marker predicting 30-day mortality-odds ratio 1.33 (1.19-1.49, p  Conclusion: Lactate is an independent marker of severity in CAP predicting both 30-day mortality and requirement for MV/VS.
Phase Iia Study to Evaluate the Biological Activity of Aslan001 in Her-1/2 Co-Expressing or Her-2 Amplified Advanced Gastric Cancer
Authors: J. Kim, S. Im, K. Lee, J.W. Kim, K. Lee, S. Han, T. Kim, I.S. Choi, D. Oh, N. Lee, C. Song, M. Foster, M. McHale, A. Barge, W.H. Kim, Y. Bang
Journal: Annals of Oncology (2014)
Spontaneous Cholangiomas in Strain C3H-A&lt;sup&gt;vy&lt;/sup&gt;fB Mice and in Their Hybrids
Authors: G. Vlahakis, W. E. Heston
Journal: JNCI Journal of the National Cancer Institute (1971)

Strain C3H-AvyfB mice and their hybrids with strain BALB/c that are highly susceptible to hepatomas also spontaneously developed in the liver morphologically distinctive neoplasms designated cholangiomas. A series of photomicrographs all showed the same cell type: proliferation of the epithelium of large bile ducts, small duct proliferation, poorly differentiated neoplasms, and better differentiated neoplasms forming bile ducts. One of these cholangiomas metastasized and was transplantable. These neoplasms were always observed in old animals with multiple hepatomas. Strain C3H-AvyfB is the only inbred strain in which spontaneous cholangiomas have been observed except for the parent strain C3H in which a few have been observed. The occurrence of cholangiomas was usually associated with the presence of the viable yellow (Avy) or the lethal yellow (Ay) gene, indicating that these allelic genes increased susceptibility to this neoplasm, as they have been shown to increase susceptibility to other neoplasms.
Expression of human UNC5 in head and neck squamous cell carcinoma
Authors: Alice Ya-Chun Chuang, Chunyan Liu, Tony Chih-Yuan Chuang, Wayne M. Koch, William H. Westra, Joseph A. Califano
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4480 

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Recent studies have shown that DCC (Deleted in Colorectal Cancer) and UNC5 family members (UNC5A, UNC5B, UNC5C, and UNC5D in human) act as dependence receptors of Netrin-1, which induce apoptosis when unbound to their ligands. Binding of Netrin-1 to its receptors DCC and UNC5 activate p53 pathways that either upregulates (induction) or downregulates (suppression) apoptosis. The potential suppressor function of the Netrin pathway in tumorigenesis prompted us to study the expression of human UNC5 orthologues involved in the apoptosis pathway. Various cell lines (normal human oral keratinocytes OKF6 TERT1 and head and neck cancer cell lines JHU011, JHU012, JHU013, and JHU019) and two normal and eight HNSCC tissues were studied. UNC5A, UNC5B, and UNC5C were downregulated (75%, 75%, and 50% respectively) in tumor samples. These results suggest that the signaling functions of the netrin/DCC/UNC5 pathway is disrupted in HNSCC. UNC5A, UNC5B, and UNC5C receptors may represent tumor suppressor genes whose protein products inhibit tumorigenesis by inducing apoptosis.
Erlotinib Pretreatment Improves Photodynamic Therapy of Non–Small Cell Lung Carcinoma Xenografts via Multiple Mechanisms
Authors: Shannon M. Gallagher-Colombo, Joann Miller, Keith A. Cengel, Mary E. Putt, Sergei A. Vinogradov, Theresa M. Busch
Journal: Cancer Research (2015)

Aberrant expression of the epidermal growth factor receptor (EGFR) is a common characteristic of many cancers, including non-small cell lung carcinoma (NSCLC), head and neck squamous cell carcinoma, and ovarian cancer. Although EGFR is currently a favorite molecular target for the treatment of these cancers, inhibition of the receptor with small-molecule inhibitors (i.e., erlotinib) or monoclonal antibodies (i.e., cetuximab) does not provide long-term therapeutic benefit as standalone treatment. Interestingly, we have found that addition of erlotinib to photodynamic therapy (PDT) can improve treatment response in typically erlotinib-resistant NSCLC tumor xenografts. Ninety-day complete response rates of 63% are achieved when erlotinib is administered in three doses before PDT of H460 human tumor xenografts, compared with 16% after PDT-alone. Similar benefit is found when erlotinib is added to PDT of A549 NCSLC xenografts. Improved response is accompanied by increased vascular shutdown, and erlotinib increases the in vitro cytotoxicity of PDT to endothelial cells. Tumor uptake of the photosensitizer (benzoporphyrin derivative monoacid ring A; BPD) is increased by the in vivo administration of erlotinib; nevertheless, this elevation of BPD levels only partially accounts for the benefit of erlotinib to PDT. Thus, pretreatment with erlotinib augments multiple mechanisms of PDT effect that collectively lead to large improvements in therapeutic efficacy. These data demonstrate that short-duration administration of erlotinib before PDT can greatly improve the responsiveness of even erlotinib-resistant tumors to treatment. Results will inform clinical investigation of EGFR-targeting therapeutics in conjunction with PDT.
Urethral Overdilatation in Females with Lower Urinary Tract Symptoms
Authors: D M Eastwood, M Goldman, D J Farrar
Journal: Journal of the Royal Society of Medicine (1984)

The long-term results of using the Otis urethrotome as a dilator only in females with lower urinary tract symptoms are reported. Out of 103 patients, 80% were symptomatically improved or cured at initial follow up and this was maintained at 18 months in 62% of cases. Optimal, long-term results (78% improvement or cure) were obtained in the subgroup of patients who had recurrent urinary tract infections. The results compare favourably with those reported following urethrotomy. The advantages of urethral overdilatation are discussed.
A<i>COL7A1</i>variant leading to in-frame skipping of exon 15 attenuates disease severity in recessive dystrophic epidermolysis bullosa
Authors: A. Schwieger-Briel, L. Weibel, N. Chmel, J. Leppert, K. Kernland-Lang, G. Grüninger, C. Has
Journal: British Journal of Dermatology (2015)

Journal Article A COL7A1 variant leading to in‐frame skipping of exon 15 attenuates disease severity in recessive dystrophic epidermolysis bullosa Get access A. Schwieger‐Briel, A. Schwieger‐Briel Department of Dermatology Medical Center, University of Freiburg Hauptstrasse 7 Freiburg 79104 Germany Search for other works by this author on: Oxford Academic Google Scholar L. Weibel, L. Weibel Department of Paediatric Dermatology University Children's Hospital Zurich University Hospital Zurich Zurich SwitzerlandDepartment of Dermatology University Children's Hospital Zurich University Hospital Zurich Zurich Switzerland Search for other works by this author on: Oxford Academic Google Scholar N. Chmel, N. Chmel Department of Dermatology Medical Center, University of Freiburg Hauptstrasse 7 Freiburg 79104 Germany Search for other works by this author on: Oxford Academic Google Scholar J. Leppert, J. Leppert Department of Dermatology Medical Center, University of Freiburg Hauptstrasse 7 Freiburg 79104 Germany Search for other works by this author on: Oxford Academic Google Scholar K. Kernland‐Lang, K. Kernland‐Lang Department of Dermatology University Hospital Bern Bern Switzerland Search for other works by this author on: Oxford Academic Google Scholar G. Grüninger, G. Grüninger Department of Dermatology Medical Center, University of Freiburg Hauptstrasse 7 Freiburg 79104 Germany Search for other works by this author on: Oxford Academic Google Scholar C. Has C. Has Department of Dermatology Medical Center, University of Freiburg Hauptstrasse 7 Freiburg 79104 Germany Correspondence: Cristina Has. E‐mail: cristina.has@uniklinik-freiburg.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 5, 1 November 2015, Pages 1308–1311, https://doi.org/10.1111/bjd.13945 Published: 01 November 2015
Metabolic Modulation of Clear-cell Renal Cell Carcinoma with Dichloroacetate, an Inhibitor of Pyruvate Dehydrogenase Kinase
Authors: Adam Kinnaird, Peter Dromparis, Bruno Saleme, Vikram Gurtu, Kristalee Watson, Roxane Paulin, Sotirios Zervopoulos, Trevor Stenson, Gopinath Sutendra, Desmond B. Pink, Katia Carmine-Simmen, Ronald Moore, John D Lewis, Evangelos D. Michelakis
Journal: European Urology (2016)
Brain Structural Abnormalities in a Group of Never-Medicated Patients With Long-Term Schizophrenia
Authors: Wenjing Zhang, Wei Deng, Li Yao, Yuan Xiao, Fei Li, Jieke Liu, John A. Sweeney, Su Lui, Qiyong Gong
Journal: American Journal of Psychiatry (2015)

This study investigated brain morphometry in chronically ill but never-medicated schizophrenia patients and whether the relation of age to morphometric abnormalities differed from that in healthy subjects.In a cross-sectional design, high-resolution T1-weighted images were acquired from 25 schizophrenia patients with untreated chronic illness lasting 5 to 47 years and 33 matched healthy comparison subjects. Cortical thickness and gray matter volume were compared in the two groups. In regions with significant group differences, nonlinear modeling of age-related effects was used to test for accelerated decline in the patients.Schizophrenia patients had less cortical thickness in the bilateral ventromedial prefrontal cortices, left superior temporal gyrus, and right pars triangularis, relative to comparison subjects, and greater cortical thickness in the left superior parietal lobe. The relation of age to cortical thickness indicated faster age-related cortical thinning in the right ventromedial prefrontal cortex, left superior temporal gyrus, and right pars triangularis in patients than in comparison subjects, but slower thinning in the left superior parietal lobe. Gray matter volume was greater in the putamen bilaterally and smaller in the right middle temporal gyrus and right lingual gyrus of the patients, but age-related effects did not differ from those of the comparison subjects.The accelerated age-related decline in prefrontal and temporal cortical thickness in never-medicated schizophrenia patients suggests a neuroprogressive process in some brain regions. Slower age-related cortical thinning of the superior parietal cortex and striatal volumetric abnormalities unrelated to age suggest different pathological processes over time in these regions.
Tandem High-Dose Therapy in Rapid Sequence for Children With High-Risk Neuroblastoma
Authors: Stephan A. Grupp, Julie W. Stern, Nancy Bunin, Cheryl Nancarrow, Amy A. Ross, Mark Mogul, Roberta Adams, Holcombe E. Grier, Jed B. Gorlin, Robert Shamberger, Karen Marcus, Donna Neuberg, Howard J. Weinstein, Lisa Diller
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Advances in chemotherapy and supportive care have slowly improved survival rates for patients with high-risk neuroblastoma. The focus of many of these chemotherapeutic advances has been dose intensification. In this phase II trial involving children with advanced neuroblastoma, we used a program of induction chemotherapy followed by tandem high-dose, myeloablative treatments (high-dose therapy) with stem-cell rescue (HDT/SCR) in rapid sequence. PATIENTS AND METHODS: Patients underwent induction chemotherapy during which peripheral-blood stem and progenitor cells were collected and local control measures undertaken. Patients then received tandem courses of HDT/SCR, 4 to 6 weeks apart. Thirty-nine patients (age 1 to 12 years) were assessable, and 70 cycles of HDT/SCR were completed. RESULTS: Pheresis was possible in the case of all patients, despite their young ages, with an average of 7.2 × 10 6 CD34 + cells/kg available to support each cycle. Engraftment was rapid; median time to neutrophil engraftment was 11 days. Four patients who completed the first HDT course did not complete the second, and there were three deaths due to toxicity. With a median follow-up of 22 months (from diagnosis), 26 of 39 patients remained event-free. The 3-year event-free survival rate for these patients was 58%. CONCLUSION: A tandem HDT/SCR regimen for high-risk neuroblastoma is a feasible treatment strategy for children and may improve disease-free survival.
Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events
Authors: Rury R. Holman, Steven M. Haffner, John J. McMurray, M. Angelyn Bethel, Björn Holzhauer, Tsushung A. Hua, Yuri Belenkov, Mitradev Boolell, John B. Buse, Brendan M. Buckley, Antonio R. Chacra, Fu Tien Chiang, Bernard Charbonnel, Chun Chung Chow, Melanie J. Davies, Prakash Deedwania, Peter Diem, Daniel Einhorn, Vivian Fonseca, Gregory R. Fulcher, Zbigniew Gaciong, Sonia Gaztambide, Thomas Giles, Edward Horton, Hasan Ilkova, Trond Jenssen, Steven E. Kahn, Henry Krum, Markku Laakso, Lawrence A. Leiter, Naomi S. Levitt, Viacheslav Mareev, Felipe Martinez, Chantal Masson, Theodore Mazzone, Eduardo Meaney, Richard Nesto, Changyu Pan, Rudolf Prager, Sotirios A. Raptis, Guy E.H.M. Rutten, Herbert Sandstroem, Frank Schaper, Andre Scheen, Ole Schmitz, Isaac Sinay, Vladimir Soska, Steen Stender, Gyula Tamás, Gianni Tognoni, Jaako Tuomilehto, Alberto S. Villamil, Juraj Vozár, Robert M. Califf
Journal: New England Journal of Medicine (2010)

The ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown.In a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide (up to 60 mg three times daily) or placebo, in a 2-by-2 factorial design with valsartan or placebo, in addition to participation in a lifestyle modification program. We followed the participants for a median of 5.0 years for incident diabetes (and a median of 6.5 years for vital status). We evaluated the effect of nateglinide on the occurrence of three coprimary outcomes: the development of diabetes; a core cardiovascular outcome that was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome, hospitalization for unstable angina, or arterial revascularization.After adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P=0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P=0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P=0.16). Nateglinide did, however, increase the risk of hypoglycemia.Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.)
Inflammation in chronic thromboembolic pulmonary hypertension: accomplice or bystander in altered angiogenesis?
Authors: Paul M. Hassoun
Journal: European Respiratory Journal (2015)

Chronic thromboembolic pulmonary hypertension (CTEPH) is not an uncommon cause of pre-capillary pulmonary hypertension (PH). It is thought to be a long-term complication of symptomatic or asymptomatic pulmonary embolism (PE) or venous thromboembolism (VTE) [1–3]. It now appears clear from a retrospective analysis of large European registries [4] and an international prospective registry [5] that CTEPH, as its name indicates, is somehow associated with one or multiple thromboembolic events. However, the reason why a minority of patients (∼0.1–9%) [6, 7] who suffer an initial VTE or PE eventually develop CTEPH while the vast majority manage to resolve their clot and resume normal life remains an enigma. Some clues into the aetiology of the disease are provided by the identification of predisposing factors found in epidemiological studies [4], such as infection (osteomyelitis) and malignancy, indwelling catheters or ventriculo-atrial shunts, splenectomy, chronic inflammatory conditions ( e.g. inflammatory bowel disease), and genetic predisposition involving the coagulation system [4, 6]. Evidence for the role of inflammation in the pathogenesis of PAH: a new study demonstrates inflammation in CTEPH <http://ow.ly/OxixF>
The identity and Work of the Ancient Egyptian Surgeon
Authors: Richard Sullivan
Journal: Journal of the Royal Society of Medicine (1996)

That a well-developed and hierarchical medical profession existed in Pharaonic Egypt is without doubt. What is a matter of contention is the existence of a recognizable surgical profession, or even of the practice of surgery by medically qualified personnel. Palaeoarchaeological specimens that demonstrate some form of surgical procedure are rare. Medical papyri and the treatises of the historians of antiquity provide a far more reliable source of information on surgical practice. They have indicated possible titles for surgeons, and the types of instruments used.
Depression and excessive daytime sleepiness en obstructive sleep apnea patients
Authors: Aura Macias, Claudio Cardenas, Aura Maldonado, Carlos Talamo, Gustavo Medrano, Juan Avila, Anabel Espinoza
Journal: European Respiratory Journal (2013)

Obstructive Sleep Apnea (OSA) is the most frequent sleep-related breathing disorder. Excessive daytime sleepiness is usually a recurrent complaint in OSA patients, and continuous positive airway pressure (CPAP) may not be fully efficient in treating it. Previous studies have found association between depression and OSA, with a variable prevalence. Symptoms of both diseases may overlap, and their incorrect interpretation may hinder treatment. The aim was to determine the frequency of presentation and severity of depression and describe its relationship with excessive daytime sleepiness in patients with OSA. 345 adult patients with OSAS diagnosed by polysomnography were assessed in a cross-sectional study. The participants filled the 9-item Patient Health Questionnaire (PHQ-9) for screening of depressive symptoms. Excessive daytime sleepiness was assess with the Epworth Sleepiness Scale. Demographic data, Apnea-Hypopnea (AHI), arousal and body mass index (BMI) were collected. 37.1% patients showed risk depressive symptoms, 34.8% showed scores compatible with depression. Severity of depression correlated directly with severity of daytime sleepiness (0.264, p=0.01). BMI correlated directly with severity of AHI (0.316, p=0.01) and arousal index (0.173, p=0.01). Average oxygen saturation was inversely related to the severity of AHI (-0,457, p=0.01). OSA patients have an increased frequency and severity of depression than those of general population, and depression is independently associated with increased daytime sleepiness. Depression screening should be indicated in all patients with OSA, especially those in whom daytime sleepiness persists despite CPAP treatment, before considering wake-promoting drugs.