tbuckley/cabot-search huggingface dataset:
Matrix Metalloproteinases-1 and -8 Improve the Distribution and Efficacy of an Oncolytic Virus
Authors: Wilson Mok, Yves Boucher, Rakesh K. Jain
Journal: Cancer Research (2007)

Oncolytic viral vectors show enormous potential for the treatment of many solid tumors. However, these vectors often suffer from insufficient delivery within tumors, which limits their efficacy in both preclinical and clinical settings. We have previously shown that tumor collagen can significantly hinder diffusion, and that its degradation can enhance the distribution and efficacy of an oncolytic herpes simplex virus (HSV) vector. Here, we identify two members of the matrix metalloproteinase (MMP) family of enzymes, MMP-1 and MMP-8, which can modulate the tumor matrix and enhance HSV delivery and efficacy. We show that overexpression of MMP-1 and MMP-8 in the human soft tissue sarcoma HSTS26T leads to a significant depletion of tumor-sulfated glycosaminoglycans. This increases the hydraulic conductivity of these tumors and enhances the flow of virus during injection. In control tumors, injected virus accumulates primarily in the periphery of the tumor. In contrast, we observed a more widespread distribution of virus around the injection site in MMP-1- and MMP-8-expressing tumors. Due to this enhanced vector delivery, MMP-expressing tumors respond significantly better to oncolytic HSV treatment than control tumors. Thus, these findings introduce a new approach to improve the delivery and efficacy of oncolytic viral vectors: modulation of tumor glycosaminoglycans to enhance convection.
The Next Transformation in the Delivery of Health Care
Authors: Jerome P. Kassirer
Journal: New England Journal of Medicine (1995)

Despite the perils of predicting the future of our health care system, many people have weighed in on how they expect the delivery of care to evolve. Such predictions are usually based on the conspicuous trend toward industrial-size delivery networks involving large populations enrolled in managed-care plans, vertically integrated medical center conglomerates, and a few giant insurance companies.13 In my view, several subtle trends will have a profound influence on the delivery of health care: the rapid growth of computer-based electronic communication, the fact that a new generation is increasingly comfortable with the electronic transfer of information, and the . . .
Extracellular Ca(2+)-dependent potentiation by cocaine of serotonin- and norepinephrine-induced contractions in rat vascular smooth muscle.
Authors: C Watanabe, H Yamamoto, S Kobayashi, H Kanaide
Journal: Circulation Research (1993)

Using front-surface fluorometry, we determined the effects of cocaine on force and cytosolic Ca2+ concentration ([Ca2+]i) in the rat aorta. We also examined the effects of cocaine on 45Ca2+ influx. Cocaine (10(-7) to 10(-4) M) alone did not alter the resting level of [Ca2+]i and force. Cocaine (&lt; 10(-4) M), in a concentration-dependent manner, potentiated the 10(-6) M serotonin (5-HT)-induced or 10(-8) M norepinephrine (NE)-induced sustained increase in [Ca2+]i and force in the presence of extracellular Ca2+, whereas it had no potentiating effects in Ca(2+)-free solution. Similar potentiating effects of cocaine were observed in pharmacologically denervated strips. Cocaine (10(-5) M) produced a leftward shift of concentration-response curves for both 5-HT- and NE-induced increases in [Ca2+]i and force with no effect on the maximal response or the relations between [Ca2+]i and force. Cocaine (10(-5) M also accelerated the 45Ca2+ influx during activation by 10(-6) M 5-HT or by 10(-8) M NE. Cocaine (&gt; 10(-3) M) inhibited 5-HT-, NE-, and high-K+ depolarization-induced contractions accompanied by decreases in [Ca2+]i in normal physiological salt solution and 5-HT- or NE-induced transient increase in [Ca2+]i and force in Ca(2+)-free physiological salt solution. Thus, low concentrations of cocaine potentiate NE- or 5-HT-induced contraction by augmenting the increase in [Ca2+]i. These potentiating effects may derive from either an increase in the affinity of the receptors to agonists or an increase in the Ca2+ influx. On the other hand, high concentrations of cocaine (&gt; 10(-3) M) have a relaxant effect on vascular smooth muscle, as a result of a decrease in [Ca2+]i.
The Waiting Room
Authors: Devan Kansagara
Journal: Annals of Internal Medicine (2012)

On Being a Doctor17 January 2012The Waiting RoomDevan Kansagara, MD, MCRDevan Kansagara, MD, MCRFrom Portland Veterans Affairs Medical Center, Portland, OR 97239.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-156-2-201201170-00017 Audio Reading - “The Waiting Room” Audio. Listen to Dr. Kansagara read his On Being a Doctor essay, "The Waiting Room." Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Roman had been in the hospital for 7 days, and no one had visited him. He had been diagnosed with metastatic lung cancer after losing pounds from an already thin frame. He had not been very active since retirement, but the cancer left him even more sedentary, and he had to move into a nursing home. He was admitted to us on this occasion with pneumonia. Because the infection was located in his upper lung, we uncovered a distant history of tuberculosis exposure and moved him to a negative-pressure isolation room.Each morning, wearing suffocating baby-blue isolation masks, we entered ... Author, Article, and Disclosure InformationAuthors: Devan Kansagara, MD, MCRAffiliations: From Portland Veterans Affairs Medical Center, Portland, OR 97239.Corresponding Author: Devan Kansagara, MD, MCR, Oregon Health and Science University, Portland Veterans Affairs Medical Center, P3 Med, 3710 SW U.S. Veterans Hospital Road, Portland, OR 97239; e-mail, kansagar@ohsu.edu. PreviousarticleNextarticle Advertisement Audio Reading - “The Waiting Room” Audio. Listen to Dr. Kansagara read his On Being a Doctor essay, "The Waiting Room." Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 17 January 2012Volume 156, Issue 2 Page: 164-165 Keywords Emotions Hospital medicine Lung and intrathoracic tumors Nicotine Nursing homes Pneumonia Rivers Shock Tuberculosis Veteran care ePublished: 17 January 2012 Issue Published: 17 January 2012 Copyright & PermissionsCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Association of KIR Genotypes and Haplotypes with Susceptibility to Chronic Hepatitis B Virus Infection in Chinese Han Population
Authors: Zhiming Lu, Bingchang Zhang, Shijun Chen, Zhongtao Gai, Zhaolei Feng, Xiangdong Liu, Yiqing Liu, Xin Wen, Li Li, Yulian Jiao, Chunyan Ma, Song Shao, Xiangfa Cui, Guojian Chen, Jianfeng Li, Yueran Zhao
Journal: Cellular and Molecular Immunology (2008)
HIV Integration Site Selection: Targeting in Macrophages and the Effects of Different Routes of Viral Entry
Authors: Stephen D. Barr, Angela Ciuffi, Jeremy Leipzig, Paul Shinn, Joseph R. Ecker, Frederic D. Bushman
Journal: Molecular Therapy (2006)

We have studied the selection of HIV DNA integration sites in primary macrophages to investigate two questions. First, mature macrophages do not divide, allowing us to investigate whether HIV integration targeting differs between dividing cells and nondividing cells. We sequenced and analyzed 754 unique integration sites and found that integration in macrophages is favored in active transcription units (TUs), as was observed previously for other cell types. However, HIV integration in genes was slightly less favored in macrophages than in dividing PBMC or T cell lines. Second, we compared integration targeting by HIV-vector particles bearing either of two different envelope proteins (HIV R5 Env or VSV-G) to determine whether the mechanism of entry influenced subsequent integration targeting. Integration sites generated by HIV R5- or VSV-G-bearing particles showed no significant differences in their distributions in the human genome. Analysis of additional published integration site sequences also indicated that the route of entry did not affect integration site selection for other viral envelopes as well.
Effect of physical training on lipids, lipoproteins, apolipoproteins, lipases, and endogenous sex hormones in men with premature myocardial infarction
Authors: Soaira G. Mendoza, H. Carrasco, A. Zerpa, Y. Briceno, F. Rodriguez, J. Speirs, C.J. Glueck
Journal: Metabolism (1991)
Doppler ultrasound and subjective assessment of fetal activity.
Authors: W D Phillips, M E Towell
Journal: BMJ (1979)

Cryptococcal swellings and ulcer on arm.The girl became critically ill, and her high-swinging fever continued.Systemic cryptococcosis was diagnosed and treatment started with 5-fc, 2-5 mg six hourly by mouth.She did not improve, and so two weeks later intravenous amphotericin was added, 0-25 mg/kg body weight daily, and the dose doubled after the first week.After 16 days of combined treatment her leucocyte count fell below 1 1l09/l (1000/mm3), with under 30 % granulocytes.Both drugs were discontinued and six units of blood (two fresh) transfused.Her white cell count rose steadily to normal, but her fever and abscesses persisted.Nine days later miconazole was given, 600 mg eight hourly by intravenous drip for four weeks and then 750 mg thrice daily by mouth for 13 months.She tolerated miconazole well, and gradually became afebrile; her abscesses healed.Intravenous hydrocortisone, given during the acute illness, was replaced by oral prednisolone at a maintenance dose of 12-5 mg daily.Despite a raised erythrocyte sedimentation rate and minor intercurrent infections, she was well two years after the diagnosis.
Keep Our NHS Public
Authors: Jane Cassidy
Journal: BMJ (2011)

Keep Our NHS Public was founded in 2005 by the NHS Consultants’ Association, the NHS Support Federation, and the pressure group Health Emergency. It is co-chaired by the campaigning obstetrician and gynaecologist Wendy Savage and is committed to fighting the privatisation of the health service (www.keepournhspublic.com/index.php).

As the Health and Social Care Bill started to receive its second reading in the House of Lords on Tuesday 11 October, Keep Our NHS Public was urging opponents of the bill to “adopt a peer” and write to or email them with their concerns. A link on the group’s website leads to a Trades Union Congress service that randomly matches individuals with peers. This enabled critics of the bill to lobby for support this week for a demand by the peers …
Distribution of Hepatitis C Virus Genotypes Determined by Line Probe Assay in Patients with Chronic Hepatitis C Seen at Tertiary Referral Centers in the United States
Authors: Johnson Y.N. Lau
Journal: Annals of Internal Medicine (1996)

Objective: To 1) verify the validity of a new line probe assay for hepatitis C virus [HCV] genotyping and 2) determine the distribution of HCV genotypes and the association between HCV genotype and clinical variables in patients with chronic hepatitis C seen in tertiary referral centers in the United States. Design: Retrospective cross-sectional analysis. Patients: 438 patients with chronic hepatitis C from 10 tertiary referral centers. Measurements: The validity of the line probe assay was first verified against a panel of serum specimens that had previously been characterized by six different HCV genotyping methods. Specimens from all 438 patients were then genotyped using this line probe assay. The associations between HCV genotype and clinical variables were examined using analysis of variance. Pairwise testing was used when the F test showed a statistically significant difference. Nonparametric alternatives were used for variables for which normality could not be assumed. Results: The line probe assay was quick and reproducible, and it showed good concordance with other tests. In our sample, the proportions of patients with HCV types 1, 2, 3, and 4 were 71.5%, 13.5%, 5.5%, and 1.1%, respectively. Subtypes 1a and 1b were seen in approximately equal proportions of patients with HCV type 1. Mixed infection was detected in 3.7% of specimens, and 4.8% of specimens either had negative results on polymerase chain reaction or could not be typed. A higher proportion of patients with HCV type 1 than of patients with HCV-type 1 had acquired HCV through transfusion of blood products (50% compared with 25%; P < 0.001). Patients with HCV type 1 also had a longer estimated duration of infection compared with patients with HCV type 3 (P = 0.004) and type 4 (P = 0.049). Disease activity did not differ among patients infected with HCV types 1, 2, or 3. Levels of viremia were similar in patients with HCV types 1, 2, or 3, but patients with HCV type 4 had a lower level of viremia than did patients with HCV type 1 (P = 0.047). Conclusions: The line probe assay can be used in patients with chronic HCV infection in the United States. In patients with chronic hepatitis C referred to tertiary centers in the United States, type 1 is the most common HCV genotype. Disease activity and viremia levels do not differ among patients chronically infected with HCV types 1, 2, or 3.
Perivascular delivery of prolonged half-life aFGF via EVAC results in angiographic collateral development, improvement in coronary flow and function in chronic myocardial ischemia
Authors: John J. Lopez, Elazer R. Edelman, Alon Stambler, Kenneth A. Thomas, Jerry D'Salvo, Mark G. Hibberd, Ronald P. Caputo, Joseph P. Carrozza, Pamela S. Douglas, Frank W. Sellke, Michael Simons
Journal: Journal of the American College of Cardiology (1996)
Dietary Folate and the Risk of Depression in Finnish Middle-Aged Men
Authors: Tommi Tolmunen, Jukka Hintikka, Anu Ruusunen, Sari Voutilainen, Antti Tanskanen, Veli-Pekka Valkonen, Heimo Viinamäki, George A. Kaplan, Jukka T. Salonen
Journal: Psychotherapy and Psychosomatics (2004)

&lt;i&gt;Background:&lt;/i&gt; Several cross-sectional studies have focused on the low blood folate levels of depressive patients. Nevertheless, no prospective studies have been published on the association between dietary folate and depression. &lt;i&gt;Methods:&lt;/i&gt; We studied the association between dietary folate and cobalamin and receiving a discharge diagnosis of depression in a prospective follow-up setting. Our cohort was recruited between 1984 and 1989 and followed until the end of 2000, and it consisted of 2,313 men aged between 42and 60 years from eastern Finland. &lt;i&gt;Results:&lt;/i&gt; The mean intake of folate in the whole cohort was 256 µg/day (SD = 76). Those below the median of energy-adjusted folate intake had higher risk of getting discharge diagnosis of depression (RR 3.04, 95% CI: 1.58, 5.86) during the follow-up period than those who had a folate intake above the median. This excess risk remained significant after adjustment for current socioeconomic status, the baseline HPL depression score, the energy-adjusted daily intake of fibre and vitamin C, and the total fat intake. &lt;i&gt;Conclusions:&lt;/i&gt; A low dietary intake of folate may be a risk factor for severe depression. This also indicates that nutrition may have a role in the prevention of depression.
Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1
Authors: Kathryn P Burdon, Stuart Macgregor, Alex W Hewitt, Shiwani Sharma, Glyn Chidlow, Richard A Mills, Patrick Danoy, Robert Casson, Ananth C Viswanathan, Jimmy Z Liu, John Landers, Anjali K Henders, John Wood, Emmanuelle Souzeau, April Crawford, Paul Leo, Jie Jin Wang, Elena Rochtchina, Dale R Nyholt, Nicholas G Martin, Grant W Montgomery, Paul Mitchell, Matthew A Brown, David A Mackey, Jamie E Craig
Journal: Nature Genetics (2011)
New Minister's Problems — Communication in Medicine
Authors: John Lister
Journal: New England Journal of Medicine (1970)

SINCE the new Government took office there has been predictable pressure on Sir Keith Joseph, the Secretary of State for Social Services, to make his views clear on a number of issues, but in line with the other members of the Government, he has been cautious in making any firm commitments at this stage. In a Parliamentary debate before the Summer recess he was challenged by Mrs. Barbara Castle, speaking for the Opposition, to explain how he would ensure the continuing expansion of the hospital-building program and maintain the present standard of the welfare services in the face of the . . .
Immunologic Reconstitution in the Acquired Immunodeficiency Syndrome
Authors: H. CLIFFORD LANE
Journal: Annals of Internal Medicine (1985)

Although effective therapies are available for many of the infections and tumors that occur in patients with the acquired immunodeficiency syndrome (AIDS), no therapy exists for the underlying immunodeficiency. Three approaches used to treat this immunodeficiency have included wholescale immune replacement through lymphocyte transfers, bone marrow transplantation, and thymic implantation; immunologic enhancement with biologic-response modifiers, such as gamma interferon, interleukin-2, and some drugs; and antiretroviral therapy. Because of the persistence of the etiologic virus, both immune replacement and enhancement will probably be ineffective unless effective strategies are developed against the virus. Agents that have shown antiviral activity in vitro which are currently in clinical trials include suramin, heteropolyanion-23 (HPA-23), ribavirin, and alpha interferon. Foscarnet and monoclonal antibodies have yet to enter clinical trials in the United States. It is still too early to tell if any of the antiviral agents will prove of value in the management of patients with AIDS.
Military Medicine Has NATO Role in Balkans
Authors: Phil Gunby
Journal: JAMA (1996)

MILITARY MEDICAL support is available to the approximately 20 000 US Implementation Force ground troops who are spreading out along North Atlantic Treat Organization peacekeeping corridors in the former Yugoslavia. A US Army medical brigade already stationed in Europe is playing a key role. Other medical resources include the US Navy's shipboard hospital beds and the US Air Force's aeromedical evacuation system. As the US troops began to deploy, President Clinton said there "could be incidents with people [associated with various factions of the civil war] who still have not given up their hatred." The White House added that poor roads, severe weather, and millions of still-undetected land mines add to the hazards. While US troops are moving into the northeastern Bosnia area around Tuzla, the 74th Medical Group—Provisional from Wright-Patterson Air Force Base near Dayton, Ohio, has turned over United Nations (UN) hospital facilities at Zagreb, Croatia, to military
Day-care-Associated Infection: More Than Meets the Eye
Authors: Stanley H. Schuman
Journal: JAMA (1983)

Studies such as that of Hadler et al (p 48) of infections contracted at day-care centers support a growing suspicion that these infections are an important problem. Communities, large and small, are experiencing outbreaks of enteric illness— diarrheas, dysentery, giardiasis, and epidemic jaundice— reminiscent of the presanitation days of the 17th century. Plans are under way for the First International Symposium on Day-care Center—Associated Infections to be held in June 1984 in Minneapolis (Michael T. Osterholm, PhD, written communication, Nov 24, 1982). Concerned participants will include experts from universities, government agencies, and private day-care management as well as pediatricians, parents, educators, and social workers. At last count, 11.4 million youngsters are in day-care, of whom 5.1 million go to private homes served by a nonrelative; 4.0 million are served at home by a relative or nonrelative; 1.9 million attend organized small and large day-care centers.<sup>1</sup> Day-care—associated outbreaks of hepatitis
Radon and lung cancer risk: taking stock at the millenium.
Authors: J M Samet, G R Eradze
Journal: Environmental Health Perspectives (2000)

Radon is a well-established human carcinogen for which extensive data are available, extending into the range of exposures experienced by the general population. Mounting epidemiologic evidence on radon and lung cancer risk, now available from more than 20 different studies of underground miners and complementary laboratory findings, indicates that risks are linear in exposure without threshold. Radon is also a ubiquitous indoor air pollutant in homes, and risk projections imply that radon is the second leading cause of lung cancer after smoking. Recommended control strategies in the United States and other countries, which include testing of most homes and mitigation of those exceeding guideline levels, have been controversial. Further research is needed, drawing on molecular and cellular approaches and continuing the follow-up of the underground miner cohorts, and scientists should work toward constructing mechanistically based models that combine epidemiologic and experimental data to yield risk estimates with enhanced certainty.
Host defense molecule polymorphisms influence the risk for immune-mediated complications in chronic granulomatous disease.
Authors: C B Foster, T Lehrnbecher, F Mol, S M Steinberg, D J Venzon, T J Walsh, D Noack, J Rae, J A Winkelstein, J T Curnutte, S J Chanock
Journal: Journal of Clinical Investigation (1998)

Chronic granulomatous disease (CGD) is an inherited disorder of phagocyte function in which defective superoxide production results in deficient microbicidal activity. CGD patients suffer from recurrent, life-threatening infections, and nearly half develop chronic gastrointestinal (GI) complications (colitis, gastric outlet obstruction, or perirectal abscess) and/or autoimmune/rheumatologic disorders (AIDs). To identify genetic modifiers of disease severity, we studied a cohort of 129 CGD patients, in whom seven candidate genes (myeloperoxidase [MPO], mannose binding lectin [MBL], Fcgamma receptors IIa, IIIa, IIIb, TNF-alpha, and IL-1 receptor antagonist), each containing a physiologically relevant polymorphism predicted to influence the host inflammatory response, were selected for analysis. Genotypes of MPO (P = 0.003) and FcgammaRIIIb (P = 0.007) were strongly associated with an increased risk for GI complications, while an FcgammaRIIa (P = 0.05) genotype was suggestive for an association. Patients with all three associated genotypes had the highest risk for GI complications (P < 0.0001). The risk of AIDs was strongly associated with variant alleles of MBL (P = 0.01) and weakly associated with an FcgammaRIIa genotype (P = 0.04). Patients with variant forms of both MBL and FcgammaRIIa had the highest risk of developing an AID (P = 0.003).
Silent cerebral infarction in apparently normal adults
Authors: S.-C. Lee, S.-J. Park, H.-S. Park, H.-C. Gwon, D.-K. Kim, S.H. Lee, H.-S. Byun, C.-S. Chung, K.-J. Shin, J.-D. Seo, W.-R. Lee
Journal: Journal of the American College of Cardiology (1998)
SIRT1-Mediated eNAMPT Secretion from Adipose Tissue Regulates Hypothalamic NAD+ and Function in Mice
Authors: Myeong Jin Yoon, Mitsukuni Yoshida, Sean Johnson, Akiko Takikawa, Isao Usui, Kazuyuki Tobe, Takashi Nakagawa, Jun Yoshino, Shin-ichiro Imai
Journal: Cell Metabolism (2015)