tbuckley/cabot-search huggingface dataset:
Relationship of Psychiatric Illness to Impotence in Men With Diabetes
Authors: Patrick J Lustman, Ray E Clouse
Journal: Diabetes Care (1990)

Clinical data from 37 adult males with diabetes mellitus (insulin dependent, n = 22; non-insulin dependent, n = 15) who had undergone psychiatric diagnosis and peripheral nerve conduction studies were reviewed to determine whether psychiatric illness was significantly related to complaints of sexual dysfunction. Main-effects testing revealed that impotence was associated with both neuropathy (P &amp;lt; 0.01) and psychiatric illness (P &amp;lt; 0.001). Logistic regression analysis was then used to determine the independent relationships of these two variables with impotence. After controlling for the effects of neuropathy, psychiatric illness (generalized anxiety disorder and depression) remained significantly associated with sexual dysfunction (P &amp;lt; 0.01). These data allow for the hypothesis that psychiatric illness may be an important contributor to impotence in diabetic men, as it is in nondiabetic men, even when neuropathic complications of the disease are present.
The British Health Service Today
Authors: Paul F. Gemmill
Journal: New England Journal of Medicine (1958)

ON July 5, 1948, everybody in the United Kingdom — not only British citizens, but alien residents and mere tourists as well — became eligible for free medical care of all kinds, under the British National Health Service. At the very start of the Service I was a tourist in Britain, and I went back again in 1956 to make the seven-month study on which the present article is largely based.Membership in the Health Service was, and is, completely voluntary: doctors and patients alike have been free to take it or leave it. A person whose family doctor decided . . .
Tumors Arising After Organ Transplantation
Authors: Adi F. Gazdar
Journal: JAMA (1997)

Most recipients of solid organ transplantation receive immunosuppressive therapy for prolonged periods and are at greatly increased risk for tumor development. These tumors have 4 origins: (1) recurrence of malignancies existing in the recipient prior to transplantation; (2) malignancies of recipient origin arising de novo after transplantation; (3) tumors of donor origin arising de novo in the transplanted organ; and (4) preexisting tumors of donor origin transmitted inadvertently to the recipient via the transplanted organ. While in the majority of cases the presumed origin of the tumors can be surmised correctly, the correct categorization of some may be difficult or controversial. In this issue ofTHE JOURNAL, Loh et al<sup>1</sup>describe the use of molecular markers to identify the donor derivation of a metastatic prostatic carcinoma in a recipient following heart transplantation. A prostatic carcinoma was identified in the donor at autopsy after the transplant procedure had been initiated
Smuggled Wildlife Products Seized at US Airports Harbor Zoonotic Viruses
Authors: Tracy Hampton
Journal: JAMA (2012)

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TM-01 * IDENTIFICATION OF GLUCOSE-6-PHOSPHATASE ALPHA AS A KEY METABOLIC REGULATOR FOR GLIOBLASTOMA CELL INVASION
Authors: S. Abbadi, J. R. Rodarte, A. Abutaleb, E. Lavell, C. L. Smith, W. Ruff, J. Schiller, A. Olivi, A. Levchenko, H. Guerrero-Cazares, A. Quinones-Hinojosa
Journal: Neuro-Oncology (2014)

Glioblastoma (GBM) remains the most aggressive primary brain cancer in adults. Similar to other cancers, GBM cells undergo metabolic reprogramming to promote proliferation and survival. Glycolytic inhibition is widely used to target such reprogramming. However, the stability of glycolytic inhibition in GBM remains unclear. In this study, we found that the expression of glucose-6-phosphatase-α (G6PC) was elevated in GBM when compared to normal brain ) (p < 0.001). Human-derived brain tumor initiating cells (BTICs) utilize this enzyme to counteract glycolytic inhibition induced by 2-Deoxy-D-glucose (2DG) and sustain malignant progression. Down-regulation of G6PC renders the majority of these cells unable to survive glycolytic inhibition, and promotes glycogen accumulation through the activation of glycogen synthase (GYS1) and inhibition of glycogen phosphorylase (PYGL). Moreover, BTICs that survive G6PC knockdown are less aggressive (reduced migration, invasion, proliferation, and increased astrocytic differentiation) (p < 0.001). Interestingly, after performing immunohistochemistry staining for G6PC in brain sections derived from animals implanted with G6PC knockdown cells for a survival study, we found a complete rescue of its expression in the tumor cells of these animals. These results explain the absence of survival differences observed between G6PC knockdown and wild type mice. Furthermore, these findings also suggest a very important role for G6PC in cell survival, since only the cells that carried G6PC where able to survive and invade in our animal model. Collectively, our findings establish G6PC as a key enzyme with pro-malignant functional consequences that has not been previously reported in GBM and identify it as a potential therapeutic target.
Classic Kaposi sarcoma in northern Sardinia: A prospective epidemiologic overview (1977-2003) correlated with malaria prevalence (1934)
Authors: Francesca Cottoni, Maria Vittoria Masala, Cristian Pattaro, Caterina Pirodda, Maria Antonietta Montesu, Rosanna Satta, Decio Cerimele, Roberto de Marco
Journal: Journal of the American Academy of Dermatology (2006)
Mitochondrial Antibody in Primary Biliary Cirrhosis and Other Diseases
Authors: GERALD KLATSKIN
Journal: Annals of Internal Medicine (1972)

Mitochondrial antibody was detected in the serum in 84% of 188 patients with primary biliary cirrhosis, 11% of 77 with chronic active hepatitis, 6% of 33 with cryptogenic cirrhosis, and 0.8% of 1328 with other diseases involving liver, biliary tract, or collagen but in none of 332 with acute or chronic viral hepatitis. Primary biliary cirrhosis was readily excluded by liver biopsy findings in antibody-positive patients with other diseases, except chronic active hepatitis. Mitochondrial antibody provides reliable confirmatory evidence of primary biliary cirrhosis when the biopsy findings are consistent. Its hepatic lesions are distinctive but may be difficult to distinguish from those of chronic active hepatitis and cryptogenic cirrhosis, diseases that may be etiologically related in some cases. The hepatitis virus is not implicated as a cause of primary biliary cirrhosis, and the presence of mitochondrial antibody does not necessarily imply that an autoimmune process is involved in its development.
Effectiveness of Bevacizumab With First-Line Combination Chemotherapy for Medicare Patients With Stage IV Colorectal Cancer
Authors: Jeffrey A. Meyerhardt, Ling Li, Hanna K. Sanoff, William Carpenter, Deborah Schrag
Journal: Journal of Clinical Oncology (2012)

Clinical trials have shown that adding bevacizumab to cytotoxic chemotherapy improves survival for patients with colorectal cancer, although its effectiveness in the Medicare population is uncertain.Using the Surveillance, Epidemiology, and End Results (SEER) -Medicare linked database, we identified 2,526 patients with stage IV colorectal cancer diagnosed between 2002 and 2007 who received first-line combination chemotherapy with a fluoropyrimidine and either irinotecan (33%) or oxaliplatin (67%). Thirty-six percent of patients received bevacizumab with first-line therapy. The primary outcome was overall survival. Secondary outcomes were bevacizumab-associated toxicities, including the incidence of stroke, myocardial infarction, and GI perforation.In the primary cohort inclusive of patients diagnosed between 2002 and 2007, bevacizumab with combination chemotherapy was associated with improved overall survival (adjusted hazard ratio [HR], 0.85; 95% CI, 0.78 to 0.93), although the effect was more modest when restricted to years 2004 to 2007 (HR, 0.93; 95% CI, 0.84 to 1.02). The observed survival advantage of bevacizumab was more apparent with irinotecan-based chemotherapy (HR, 0.80; 95% CI, 0.66 to 0.97) than with oxaliplatin-based chemotherapy (HR, 0.96; 95% CI, 0.86 to 1.07). Combination chemotherapy with bevacizumab, versus combination chemotherapy without bevacizumab, was associated with increased risk of stroke (4.9% v 2.5%, respectively; P < .01) and GI perforation (2.3% v 1.0%, respectively; P < .01). Cardiac events and venous thrombosis were not increased with bevacizumab.The addition of bevacizumab to cytotoxic combination chemotherapy was associated with small improvement in overall survival as well as increased risk of stroke and perforation, but not cardiac events, among Medicare beneficiaries with stage IV colorectal cancer.
Abstract 5506: Trabedersen (AP 12009) for the treatment of patients with advanced tumors: A phase I/II study
Authors: Helmut Oettle, Andreas Hilbig, Thomas Seufferlein, Thomas Luger, Roland Schmid, Götz von Wichert, Esther Endlicher, Claus Garbe, Katharina C. Kaehler, Axel Hauschild, Peter Kiessling, Susanne Schmaus, Hubert Heinrichs, Karl-Hermann Schlingensiepen
Journal: Cancer Research (2011)

Abstract Background: Transforming growth factor-beta 2 (TGF-β2) regulates key mechanisms of carcinogenesis, in particular immunosuppression and metastasis. The antisense oligonucleotide trabedersen (AP 12009) specifically inhibits TGF-β2 expression. A randomized and active-controlled phase IIb study in high-grade glioma patients showed a clear survival benefit for intratumoral treatment with trabedersen over standard chemotherapy. In this study we evaluate the maximum tolerated dose (MTD), safety, pharmakokinetics, and efficacy of intravenous trabedersen treatment in patients with advanced solid tumors. Methods: In the open label, multicenter, Phase I/II study, 33 patients with advanced pancreatic carcinoma (PancCa, stage III/IV, N=23), malignant melanoma (stage III/IV, N=5), or colorectal carcinoma (stage III/IV, N=5) were enrolled in cohorts for dose-escalation. Patients were treated intravenously with trabedersen as 2nd to 4th-line therapy as monotherapy with escalating doses in 2 treatment schedules (1st schedule: 7d on, 7d off; 2nd schedule: 4d on, 10d off; up to 10 cycles). After completion of dose-escalation, further patients were enrolled for the treatment with one defined dose in the Phase II part of the study. Results: Trabedersen showed excellent safety and tolerability. The only expected adverse reaction identified is non-serious, transient and moderate thrombocytopenia. Within the 1st schedule, MTD was established at a dose of 160 mg/m2/d. In the 2nd schedule (4d on, 10d off) a well tolerated dose (140 mg/m2/d) was identified and subsequently further 14 PancCa patients were treated with this regimen. The median overall survival of PancCa patients treated 2nd-line with the 2nd schedule-140 mg/m2/d regimen (N=9) has not yet been reached and currently is 9.2 months (status Oct 2010). Further promising efficacy data include: one PancCa patient had a complete, sustained response of liver metastases and is alive 61 months after monotherapy with trabedersen; another patient is alive 31 months after treatment start (status Oct 2010). Promising efficacy was also observed in malignant melanoma patients with a current median overall survival of 13.8 months. Conclusions: Currently the study continues with the treatment of 12 patients with malignant melanoma with the 2nd schedule-140 mg/m2/d regimen. A randomized, active-controlled study in PancCA patients is in preparation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5506. doi:10.1158/1538-7445.AM2011-5506
Dynamics of wavelets and their role in atrial fibrillation in the isolated sheep heart
Authors: J Chen
Journal: Cardiovascular Research (2000)

The multiple wavelet hypothesis is the most commonly accepted mechanism underlying atrial fibrillation (AF). However, high frequency periodic activity has recently been suggested to underlie atrial fibrillation in the isolated sheep heart. We hypothesized that in this model, multiple wavelets during AF are generated by fibrillatory conduction away from periodic sources and by themselves may not be essential for AF maintenance.We have used a new method of phase mapping that enables identification of phase singularities (PSs), which flank individual wavelets during sustained AF. The approach enabled characterization of the initiation, termination, and lifespan of wavelets formed as a result of wavebreaks, which are created by the interaction of wave fronts with functional and anatomical obstacles in their path. AF was induced in six Langendorff-perfused sheep hearts in the presence of acetylcholine. High resolution video imaging was utilized in the presence of a voltage sensitive dye; two-dimensional phase maps were constructed from optical recordings. The major results were as follows: (1) the critical inter-PS/wavelet distance for the formation of rotors was 4 mm, (2) the spatial distribution of wavelets/PSs was non-random. (3) the lifespan of PSs/wavelets was short; 98% of PSs/wavelets existed for < 1 rotation, and (4) the mean number of waves that entered our mapping field (15.7 +/- 1.6) exceeded the mean number of waves that exited it (9.7 +/- 1.5; P < 0.001).Our results strongly suggest that multiple wavelets may result from breakup of high frequency organized waves in the isolated Langendorff-perfused sheep heart, and as such are not a robust mechanism for the maintenance of AF in our model.
Aortic Root Pseudoaneurysm 1 Year After Transapical Aortic Valve Implantation
Authors: Javier Cobiella, Pedro Marcos-Alberca, Ramón Bover, Luis Maroto, Jacobo Silva, Manuel Carnero, Andrea Calli, Carlos Macaya, José Zamorano, Enrique Rodrguez
Journal: Circulation (2010)
The Contribution of Increased Diabetes Prevalence and Improved Myocardial Infarction and Stroke Survival to the Increase in Treated End-Stage Renal Disease
Authors: Paul Muntner, Josef Coresh, Neil R. Powe, Michael J. Klag
Journal: Journal of the American Society of Nephrology (2003)

This study examined the extent to which the greater than threefold increase in number of treated end-stage renal disease (ESRD) cases between 1978 and 1991 is explained by increases in the prevalence of diabetes, myocardial infarction (MI) and stroke survivors, and US population size. The change in number of persons in the United States with diabetes, a history of MI or stroke, and without these conditions was estimated for 1978 and 1991 using the Second and Third National Health and Nutrition Examination Surveys. The treated ESRD incidence rate and the increase in ESRD treatment attributable to each of these populations were calculated using these estimates and data from the United States Renal Data System. In the United States, there were an estimated 4.3 and 1.2 million more persons with diabetes and a history of MI or stroke, respectively, 22.7 million more persons without these conditions, and 36,881 more incident treated ESRD cases in 1991 compared with 1978. In 1991, treated ESRD incidence rates among persons with diabetes, a history of MI or stroke, and without these conditions were 2567, 1463, and 153 cases per million person-years, respectively. In 1991, 10,183 cases of the additional 36,881 treated ESRD cases (27.6%) resulted from the higher prevalence of diabetes; 1775 (4.8%) from increased MI and stroke survival; and 2904 (7.9%) resulted from growth of the US population without these conditions. The increasing number of treated ESRD cases in the United States is partly explained by the increase in diabetes prevalence and US population growth but only minimally by MI and stroke survival.
Introduction to animal parasitology.
Authors: J. Walter Beck
Journal: JAMA (1963)

This work is a departure from the classical presentation to the student of animal parasitology. It is a reflection of the new era in parasitology, wherein the knowledge and tools of other sciences, such as biochemistry, microbiology, immunology, physiology, and so on, are brought to bear upon a field expanding beyond systematics and morphology. The author places major emphasis upon the living parasite and the host-parasite relationship. In particular, an attempt is made to analyze the factors which control the growth, maturation, and reproduction of parasites in relation to the physiology of their hosts and the properties of the environment. No attempt has been made to cover the entire field of human or animal parasitology. Many of the better known human parasites are considered as are the animal parasites which are easy to obtain from the animal kingdom for the purpose of presenting the dynamics of the groups involved. Morphology
Selective NOD1 Agonists Cause Shock and Organ Injury/Dysfunction<i>In Vivo</i>
Authors: Neil Cartwright, Oliver Murch, Shaun K. McMaster, Mark J. Paul-Clark, David A. van Heel, Bernhard Ryffel, Valerie F. J. Quesniaux, Timothy W. Evans, Christoph Thiemermann, Jane A. Mitchell
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

NLRs (nucleotide oligomerisation domain [NOD] proteins containing a leucine-rich repeat) are cytosolic pattern recognition receptors. NOD1 senses diaminopimelic acid-containing peptidoglycan present in gram-negative bacteria, whereas NOD2 senses the muramyl dipeptide (MDP) present in most organisms. Bacteria are the most common cause of septic shock, which is characterized clinically by hypotension resistant to vasopressor agents. In animal models, gram-negative septic shock is mimicked by lipopolysaccharide (LPS), which signals through Toll-like receptor 4 (TLR4) and its adaptor MyD88. The role of NLRs in the pathophysiology of septic shock is not known.To compare the effects of selective NOD1 agonists with LPS in vivo.Vascular smooth muscle cells or whole aortas from wild-type or genetically modified mice were stimulated in vitro with agonists of NOD1 (FK565) or NOD2 (MDP). Vasoconstriction was measured using wire myography. Nitric oxide (NO) formation was measured using Griess reaction and NO synthase-II protein by Western blotting. In vivo, blood pressure, heart rate, and urine output were measured in sham-, LPS-, or FK565-treated animals. Biomarkers of end-organ injury, coagulation activation, NO, and cytokines were measured in plasma.FK565, but not MDP, induced NO synthase-II protein/activity in vascular smooth muscle and vascular hyporeactivity to pressor agents. FK565 had no effect on vessels from NOD1(-/-) mice, but was active in vessels from TLR4(-/-), TLR2(-/-), or MyD88(-/-) mice. FK565 induced hypotension, increased heart rate, and caused multiple (renal, liver) injury and dysfunction in vivo.Activation of NOD1 induces shock and multiple organ injury/dysfunction.
Abstract 5057: Activation of stroma-derived matrix metalloproteinases (MMPs) in a model of gastric cancer.
Authors: Sandhir Kandola, Christopher Holmberg, Bart Ghesquiere, Francis Impens, Kris Gevaert, J. Dinesh Kumar, Nicole Cash, Peter Hegyi, Nikolina Vlatkovic, Timothy Wang, Graham Dockray, Andrea Varro
Journal: Cancer Research (2013)

Abstract Gastric cancer is the second commonest cause of cancer-related death worldwide. Within these tumors, it is increasingly recognised that signaling between myofibroblasts, an important stromal cell type, and cancer cells results in proliferation, invasion and metastasis. However, little is known of the range of proteins secreted by stromal cells ie their secretome, or the contribution of proteases in shaping the extracellular milieu ie the cancer degradome. Using SILAC labeling and combined fractional diagonal chromatography (COFRADIC) we identified and quantified differential abundance and appearance of neo-N-termini (ie cleavage products) in the secretomes of gastric cancer-associated myofibroblasts (CAMs) compared with myofibroblasts from adjacent tissue (ATMs). There was decreased abundance of many proteins in CAM secretomes, but a small sub-set exhibited increased abundance including matrix metalloproteinases (MMP) -1 and -3. Cancer-restricted proteolytic cleavages included cleavage in the prodomains of MMP-1, -2 and -3 consistent with activation. Western blot, enzyme activity and cancer cell migration assays verified significantly increased abundance of active MMP-1, -2 and -3 in CAM media. To establish the in vivo relevance of these findings we utilized a model in which primary gastric CAMs stimulate growth of MKN45 gastric cancer cells in xenografts in nude mice. MMP activity was imaged by fluorescence molecular tomography (FMT) employing MMPSense750 FAST™, which produces a fluorescent signal following MMP cleavage. CAMs enhanced xenograft growth by 6-fold (mean ± SEM, 29.6±21.1 vs 196.8±32.2 mm3 n=12, p=0.004). Using an experimental design that achieved similar volumes for tumors containing MKN45 cells alone and those containing MKN45+CAM, FMT assessment of tumor-related MMP activity in vivo indicated a two-fold increase in CAM-MKN45 xenografts compared with MKN45 cells alone (0.9±0.4 vs 1.8±0.8 fmol/mm3). Stromal cell secretomes therefore contribute to the remodelling of the cancer cell microenvironment by activation of MMPs with consequences for cell migration and tumor growth. This system has potential for in vivo screening of anti-cancer therapies directed at the inhibition of stroma-stimulated tumor growth. Citation Format: Sandhir Kandola, Christopher Holmberg, Bart Ghesquiere, Francis Impens, Kris Gevaert, J. Dinesh Kumar, Nicole Cash, Peter Hegyi, Nikolina Vlatkovic, Timothy Wang, Graham Dockray, Andrea Varro. Activation of stroma-derived matrix metalloproteinases (MMPs) in a model of gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5057. doi:10.1158/1538-7445.AM2013-5057