tbuckley/cabot-search huggingface dataset:
A gene based risk score for smokers and ex-smokers identifies those most susceptible to lung cancer.
Authors: Robert Young, Raewyn Hopkins, Bryan Hay, Peter Black, Micheal Epton, Gregory Gamble
Journal: Cancer Research (2008)

3128   Exposure to cigarette smoking is central to the development of lung cancer. Other risk factors include increasing age, impaired lung function, family history of lung cancer and asbestos exposure.   Methods : In this two stage case-control study 446 lung cancer cases and 484 healthy smoker controls were recruited. 156 genetic markers (SNPs) implicated in lung cancer were screened in our test cohort of 439 smokers and ex-smokers. 30 SNPs whose genotypes (co-dominant or recessive model) were associated with either the healthy smokers (protective) or lung cancer (susceptibility) phenotype were identified. After genotyping this 30 SNP panel in a second cohort of 491 subjects, 19 SNPs were chosen and assigned a simple composite genetic score that was combined with scores for age, history of COPD and family history of lung cancer, weighted according to our multivariate regression analysis (n=930 total subjects).   Results : The lung cancer risk score was linearly related to the likelihood of lung cancer with odds ratios (referenced against the lowest score quintile) ranging from 1 to 29 in the highest quintile. On receiver operator curve analyses, the AUC was 0.78 and the frequency distribution showed bimodal separation between healthy smokers and lung cancer cases. Utility of the score was not affected by effects of age, smoking history or lung function.   Conclusion : We suggest that genetic data may be combined with other risk variables to define smokers or ex-smokers at risk of lung cancer for targeted interventions such as smoking cessation and early detection of lung cancer.
Abstract 13620: Aortic Distensibility, Assessed by MRI, is Decreased in Adolescents with Type 1 Diabetes Mellitus and Elevated LDL-C
Authors: Michael A McCulloch, Samuel Gidding, J. Atilio Canas, Judith Ross, Jobayer Hossain, Michael Caulfield, Kaitlin Sikes, Christopher Sibley, Alain De Cesare, Nelly Mauras
Journal: Circulation (2012)

Background: Children with type 1 diabetes (T1DM) have increased risk for accelerated cardiovascular disease (CVD) development. CVD remains the principal risk of mortality in T1DM, making its preven...
SUBACUTE BACTERIAL ENDOCARDITIS
Authors: J. H. Musser
Journal: Annals of Internal Medicine (1933)

ExcerptThe fact that I have seen in the Charity Hospital in New Orleans in the past two years many more cases of subacute bacterial endocarditis than I remember ever having seen in the past, has led me to review the history of 14 cases that I have observed in this period of time in order to present to you certain features of a disease which, in one section of the country at least, seems to be increasingly prevalent. Some years ago Blumer1wrote that "it is difficult to say whether the disease is actually increasing or whether there is merely...
Medical student electives and infectious diseases
Authors: J. Meadway, S. T Green
Journal: BMJ (1999)

Editor—Gamester et al found that only 34% of students visiting a country with a high prevalence of HIV purchased zidovudine, probably because of the cost (£40). They recommended that medical schools should consider paying for the drug.1

However, zidovudine alone is no longer the standard postexposure prophylaxis. United Kingdom guidelines now state that healthcare workers with high risk exposure to HIV should be advised to take a combination of zidovudine 200 mg three times a day or 250 mg twice daily plus lamivudine 150 mg twice daily plus indinavir 800 mg three times a day.2

Indinavir should be taken 1 hour before or 2 hours after a meal.3 Nephrolithiasis may occur with indinavir, and manufacturers recommend drinking 1.5-2 litres of fluid daily during treatment. Reports suggest that more nephrolithiasis occurs in warm weather and that the volume should be increased in warm climates,4 which would be relevant to many students travelling to hot countries. Advice must be given to anyone who may take treatment which includes indinavir.

Today’s doctors expect adequate advice and nationally recommended treatment. We should offer no less to the doctors of tomorrow.
Early occurrence of epidermal growth factor receptor Mutation in lung adenocarcinoma: Comparison between pulmonary atypical adenomatous hyperplasia and adenocarcinoma
Authors: Toshiyuki Kozuki, Akiko Hisamoto, Nagio Takigawa, Masahiro Tabata, Yoshihiko Segawa, Masao Nakata, Shigeki Umemura, Kadoaki Ohashi, Katsuyuki Kiura, Kenji Eguchi, Hiroshi Ueoka, Mitsune Tanimoto
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4544 

Purpose: Recently, the somatic mutations in tyrosine kinase (TK) domain of epidermal growth factor receptor (EGFR) gene has been identified as predictor of tumor response to gefitinib or erlotinib in non-small-cell lung cancer (NSCLC). Also, much evidence has accumulated that the EGFR are strongly implicated in the development of lung adenocarcinoma (ADC). However, the frequency of these mutations in pulmonary precancerous lesion such as atypical hyperplasia (AAH) was unknown. Purpose of this study is to elucidate the implication of EGFR mutation in the early carcinogenesis of lung cancer. Methods: We retrospectively examined the EGFR mutations in 9 AAH and 31 adenocarcinoma (ADC) lesions obtained from 34 Japanese patients who were treated with surgery. The EGFR gene mutations in exon 18 - 21 were analyzed with polymerase chain reaction and direct sequence methods. All patients with AAH were female. Nine were male and 25 were female with ADC. Nine patients had synchronous or metachronous multiple lesions. One patient had synchronous triple ADC’s, two patients had synchronous double ADC’s, two patients had metachronous two ADC, and three patients hsd synchronous AAH and ADC. Results: EGFR mutations were detected in four (44%) of nine AAH lesions and seven (23%) of 31 ADC lesions (P=0.34). One of each lesions were revealed to harbor new unknown EGFR mutation. In nine patients who had multiple lesions, six patients harbored the EGFR gene mutation. However the patterns of EGFR gene mutation in multiple lesions of same patient were not identical. For example, synchronous AAH and ADC in one patient harbored same point mutation in exon 19, however, additional point mutation in exon 20 was also detected in this AAH lesion. Conclusions: Frequency of EGFR TK domain mutations in AAH and ADC were similar. Multiple lesions in same patient did not always harbored same EGFR gene mutations. These results indicate that these EGFR mutations occurred early phase of lung carcinogenesis such as AAH
Inhibition of hepatic stellate cells by bone marrow-derived mesenchymal stem cells in hepatic fibrosis
Authors: Yoon Ok Jang, Baek Gyu Jun, Soon Koo Baik, Moon Young Kim, Sang Ok Kwon
Journal: Clinical and Molecular Hepatology (2015)

Background/Aims Therapies involving bone-marrow-derived mesenchymal stem cells (BM-MSCs) have considerable potential in the management of hepatic disease. BM-MSCs have been investigated in regenerative medicine due to their ability to secrete various growth factors and cytokines that regress hepatic fibrosis and enhance hepatocyte functionality. The aim of this study was to determine the antifibrosis effect of BM-MSCs on activated hepatic stellate cells (HSCs) and the mechanism underlying how BM-MSCs modulate the function of activated HSCs. Methods We used HSCs in both direct and indirect co-culture systems with BM-MSCs to evaluate the antifibrosis effect of BM-MSCs. The cell viability and apoptosis were evaluated by a direct co-culture system of activated HSCs with BM-MSCs. The activations of both HSCs alone and HSCs with BM-MSCs in the direct co-culture system were observed by immunocytochemistry for alpha-smooth muscle actin (α-SMA). The levels of growth factors and cytokines were evaluated by an indirect co-culture system of activated HSCs with BM-MSCs. Results The BM-MSCs in the direct co-culture system significantly decreased the production of α-SMA and the viability of activated HSCs, whereas they induced the apoptosis of activated HSCs. The BM-MSCs in the indirect co-culture system decreased the production of transforming growth factor-β1 and interleukin (IL)-6, whereas they increased the production of hepatocyte growth factor and IL-10. These results confirmed that the juxtacrine and paracrine effects of BM-MSCs can inhibit the proliferative, fibrogenic function of activated HSCs and have the potential to reverse the fibrotic process by inhibiting the production of α-SMA and inducing the apoptosis of HSCs. Conclusions These results have demonstrated that BM-MSCs may exert an antifibrosis effect by modulating the function of activated HSCs. Keywords: Bone-marrow-derived mesenchymal stem cell; Cirrhosis; Hepatic fibrosis
The Man Who Declined the Presidency: Owen D. Young
Authors: Irving S. Wright
Journal: Annals of Internal Medicine (1966)

Medical History1 October 1966The Man Who Declined the Presidency: Owen D. YoungIRVING S. WRIGHT, M.D., F.A.C.P.IRVING S. WRIGHT, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-65-4-843 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt was early in July 1931 when, as a young physician, I found myself in the midst of a drama which may have had a profound effect on the course of American and even international history. It came about in this way. I was serving as an assistant physician to Dr. Arthur Chace, then at the peak of his professional career. He was Professor of Medicine at the New York Postgraduate Medical School (now associated with New York University). He had been president of numerous medical societies and was to be President of the New York Academy of Medicine. As... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *This bit of history is now published for the first time after consultation and approval by members of the family of Owen D. Young. We feel that it should be recorded as a significant detail of American history.From the Department of Medicine, the Cornell University Medical College, New York, N. Y.Dr. Wright is the President of the American College of Physicians.Requests for reprints should be addressed to Irving S. Wright, M.D., 450 E. 69 St., New York, N. Y. 10021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1966Volume 65, Issue 4Page: 843-848 ePublished: 1 December 2008 Issue Published: 1 October 1966 PDF downloadLoading ...
Characteristics of thymidine monophosphate kinase and its role in the cellular metabolism of anticancer and antiviral thymidine analogs.
Authors: Rong Hu, Ling Li, Bart Degreve, Ginger E. Dutschman, Elizabeth A. Gullen, Yung-Chi Cheng
Journal: Cancer Research (2004)

2026   Human thymidylate kinase (TMP kinase) phosphorylates thymidine monophosphate (TMP) to thymidine diphosphate (TDP), which is essential in both the  de novo  and salvage pathways of DNA synthesis of the thymidine triphosphate (TTP). The DNA fragment encoding the TMP kinase from Hela cells was cloned, expressed and purified. No difference was observed in the enzymatic characteristics with regard to natural substrate between the recombinant TMP kinase and TMP kinase purified from CEM cells. The Km values of TMP, FdUMP, AZTMP, d4TMP, L-FMAUMP, D-FMAUMP for recombinant TMP kinase were in the following order of AZTMP   D-FMAUMP > FdUMP > d4TMP > L-FMAUMP > AZTMP. These TMP analogs were competitive inhibitors with respect to TMP in the order of D-FMAUMP >> AZTMP > L-FMAUMP > d4TMP. L-BrOddUMP and L-IOddUMP were not measurable substrates and inhibitors of the recombinant TMP kinase. The plasmid harboring the DNA fragment of TMP kinase was transfected into human colorectal carcinoma (RKO) cells, which permitted the expression of the TMP kinase to be closely regulated in response to varying concentrations of doxycyclin (Dox). The level of the TMP kinase activity directly depended on the protein amount of the enzyme. The TMP kinase was found to be predominantly localized in the cytoplasm of the transfected cells harboring the DNA fragment of TMP kinase, with less TMP kinase detected in the Golgi, mitochondria and nuclei. When the cells were treated with AZT, d4T and L-FMAU, the diphosphate and triphosphate metabolites of these analogs were increased in accordance with the increase of the TMP kinase in cells. The cytotoxicity of AZT increased directly with the activity of the induced TMP kinase. The IC 50  values of AZT were decreased from 26μM to 1.25μM in cells when the TMP kinase was increased 10-fold. As for FUdR and D-FMAU, the cytotoxicities were increased only when the TMP kinase was induced to 10-fold. The cytotoxicity of d4T did not significantly vary with the increase of the TMP kinase activity. No L-FMAU cytotoxicity was found at a concentration up to 200μM in induced cells. In summary, this study indicated the importance of the TMP kinase in the metabolism of these thymidine analogs and proved that TMP kinase was one of the limiting factors for the cytotoxicity of AZT, but not for that of d4T or L-FMAU. (This study was supported by NIH grant AI 38204 and CA63477)
Children's views should have been represented in discussion
Authors: W E Osmun
Journal: BMJ (1996)

These studies show the dangers of making ethical pronouncements in an empirical vacuum.There is a pressing need for more research on how proxy decision makers arrive at their recommendations for treatment.With regard to bone marrow donation, parents have several obligations.Not only do they have to keep the best interests of the two children in mind but they also have to come to a mutually acceptable solu- tion that will at least maintain their partnership.Just as there is now much emphasis on evidence based medical practice, so too ought there to be more interest in evidence based ethical practice.
Abstract 518: Cyclophilin A is a Novel Pro-Inflammatory Cytokine that Accelerates Development of Atherosclerosis
Authors: Kimio Satoh, Michael R O’Dell, Duan-fang Liao, Zhaoqiang Cui, Patrizia Nigro, Amy Mohan, Jeffrey Alexis, Bruce Goldman, Bradford C Berk
Journal: Circulation (2008)

Background - Cyclophilin A (CyPA), a member of the immunophilin family, is highly expressed in vascular smooth muscle cells (VSMC) in mice and humans. CyPA is secreted in response to reactive oxygen species (ROS) and also is a positive regulator of helper T (Th) profile promoting differentiation of Th0 cells into Th1 lymphocytes (increased IFN-γ The development of atherosclerosis involves vascular inflammatory cytokine release, inflammatory cell migration/activation, and altered Th1/Th2 profile. Based on the role of CyPA in ROS signaling and Th profile we hypothesized that CyPA would promote atherosclerosis. Methods and Results - We compared atherosclerosis development in ApoE −/− and ApoE −/− CyPA −/− mice using two different models. In ApoE −/− mice fed a high-fat diet for 16 weeks, atherosclerosis assessed by oil-red O (ORO) staining was significantly greater in ApoE −/− mice compared to ApoE −/− CyPA −/− mice (%ORO, en face aorta; 23.1±5.5 vs. 6.8±3.2, P &lt;0.01). Immunostaining of atherosclerotic lesions in the aortic cusp revealed the co-localization of CyPA, CD45, and MCP-1, suggesting the importance of CyPA for inflammatory cell recruitment and cytokine production. Angiotensin II infusion (AngII, 1000 ng/min/kg, 4 weeks) significantly increased atherosclerosis area in ApoE −/− mice, which was significantly less in ApoE −/− CyPA −/− mice (%ORO, en face aorta; 11.1±4.6 vs. 4.0±2.8, P&lt;0.01). ApoE −/− mice showed significant increases in vascular MCP-1 expression, VCAM-1 expression, and inflammatory cell migration to the aortic wall, all of which were significantly less in ApoE −/− CyPA −/− mice. Cytokine/chemokine array analysis revealed that AngII significantly increased secretion of numerous cytokine/chemokines from ApoE −/− spleno-cytes, which was significantly less in ApoE −/− CyPA −/− splenocytes. Mechanistic studies in vitro revealed that AngII enhanced CyPA secretion from mouse aortic VSMC. Finally, expression of CyPA was significantly increased in atherosclerotic plaques of patients with acute coronary syndromes. Conclusion - CyPA is a novel mediator of atherosclerosis by promoting inflammatory cytokine/chemokine secretion, adhesion molecule expression, and inflammatory cell migration. This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).
Providing intensive care
Authors: J. Michael, R. Hibbert, J. Plewes
Journal: BMJ (1996)

Low blood pressure is unlikely to be complication of dementia process EDrrOR,-Zhenchao Guo and colleagues report an association between low blood pressure and different types of dementia, including Alzheimer's disease.' Adults with Down's syndrome have a high prevalence of Alzheimer's disease2; they also have significantly lower diastolic and systolic blood pressures than the general population.3We reviewed data from a five year prospective longi- tudinal study investigating aging in a cohort of adults with Down's syndrome to explore a possible association between low blood pressure and Alzheimer's disease.Measurements of blood pressure and evidence used in making a diagnosis of Alzheimer's disease according to criteria in the International Classification of Diseases (10th revision)4 were available for 80 subjects aged over 45.Twenty one subjects fulfilled the criteria for Alzheimer's disease.The mean age of the group without dementia was 52.6 years and that of the group with dementia was 55.0 years (t=0.32,P=0.75).The mean systolic blood pressure was 109.5 mm Hg and 114.7 mm Hg respectively (t=1.6,P=0.25), and the mean diastolic blood pressure was 76.6 mm Hg and 75.9 mm Hg respectively (t=0.32,P=0.75).Thus there was no significant difference in either blood pressure between the two groups.Incessant hypoperfusion due to persistent low blood pressure in adults with Down's syndrome may predispose to the development of neuropathological changes of Alzheimer's disease.We found no evidence, however, that low blood pressure is a complication of the clinical demen- tia process in people with Down's syndrome.
Abstract 18192: Free Radical Scavenger Edaravone Inhibited Both Aneurysmal Formation and Progression in Rat Abdominal Aortic Aneurysm Model
Authors: Keisuke Morimoto, Tomomi Hasegawa, Akiko Tanaka, Naoto Morimoto, Yutaka Okita, Kenji Okada
Journal: Circulation (2011)

Objective: Effective pharmaceutical treatment for abdominal aortic aneurysm (AAA) has not been established. Recent studies have reported that reactive oxygen species (ROS) are excessively expressed in the aneurysm wall. However, whether ROS play a crucial role in the aneurysm formation and its growth still remains unknown. We investigate ROS inhibition with the free radical scavenger edaravone effectively prevents aneurysm formation. Methods: Thirty male Sprague-Dawely rats were used to create experimental AAA model. Rats were divided into three groups; group C (control) received an intraperitoneal injection of saline at 30 minutes prior to the aneurysm preparation, group E (edaravone-early-treated) received an intraperitoneal injection of edaravone 5 mg/kg/day at 30 minutes prior to the aneurysm preparation, and the edaravone-late-treated group (group L) received the same dose of edaravone at 7 days after AAA preparation. At day 7, ROS production was semiquantified by dihydroethidium staining, and the oxidative product of DNA induced by ROS, 8-hydroxydeoxyguanosine (8-OHdG), by immunohistochemical staining. The dilatation ratio of AAA at day 28 was calculated. Results: At day 7, dihydroethidium staining of aneurysm wall showed that ROS expression was significantly suppressed in group E compared with groups C and L (2.1±0.7 in group E, 4.3±1.8 in groups C and L, p=0.02). Positive cell count of 8-OHdG was significantly lower in group E than that in groups C and L. The aortic dilatation ratio (%) at day 28 in groups E was significantly lower than that in group C (36.7±2.0 vs. 104.7±16.0, p&lt; 0.001) and in group L was significantly lower than that in group C (53.1±2.9 vs. 104.7±16.0, p&lt; 0.001). Conslusion: ROS play a crucial role in the aneurysm formation. Edaravone treatment starting even at 7 days after aneurysm preparation completely inhibited aneurysmal growth. Edaravone could be effective pharmaceutical agent for AAA in clinical practice.
Abstract 79: Minimal Hemodynamic Effects of Varying Respiratory Rate and Tidal Volume During CPR but Large Impact on End Tidal PCO2
Authors: Raúl J Gazmuri, Iyad M Ayoub, Jeejabai Radhakrishnan, Jill R Motl, Madhav P Upadhyaya
Journal: Circulation (2010)

Background: Ventilation with excessive respiratory rate is considered detrimental during CPR, because it increases intrathoracic pressure limiting venous return and thus the generation of forward blood flow. We hypothesized that ventilation with excessive tidal volume is also detrimental, and examined in a swine model of VF the hemodynamic effects of various respiratory rates and tidal volumes during CPR while concomitantly examining the effect on end-tidal pCO2 (PETCO2), a useful surrogate measurement of blood flow during low-flow states. Methods: VF was induced in male pigs and left untreated for 8 minutes before providing 8 minutes of uninterrupted chest compressions (100/min) with a LUCASTM device. Four groups of 4 pigs each were randomized to one of four combinations of respiratory rate (bpm) and tidal volume (ml/kg); i.e., 10/6, 10/18, 33/6, or 33/18. The breaths were delivered using an 840 Nellcor Puritan Bennett ventilator. Results: Data (mmHg, mean ± SD) are shown in the order listed above. Venti...