tbuckley/cabot-search huggingface dataset:
Gene Therapy of βc-Deficient Pulmonary Alveolar Proteinosis (βc-PAP): Studies in a Murine in vivo Model
Authors: Veronika Kleff, Ursula R Sorg, Carsten Bury, Takuji Suzuki, Ina Rattmann, Moran Jerabek-Willemsen, Christopher Poremba, Michael Flasshove, Bertram Opalka, Bruce Trapnell, Uta Dirksen, Thomas Moritz
Journal: Molecular Therapy (2008)

Pulmonary alveolar proteinosis (PAP) due to deficiency of the common β-chain (βc) of the interleukin-3 (IL-3)/IL-5/granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors is a rare monogeneic disease characterized by functional insufficiency of pulmonary macrophages. Hematopoietic stem cell gene therapy for restoring expression of βc-protein in the hematopoietic system may offer a curative approach. Toward this end, we generated a retroviral construct expressing the murine βc (mβc) gene and conducted investigations in a murine model of βc-deficient PAP. Functional correction of mβc activity in mβc-/- bone marrow (BM) cells was demonstrated by restoration of in vitro colony formation in response to GM-CSF. In addition, in a murine in vivo model of mβc-deficient PAP mβc gene transfer to hematopoietic stem cells not only restored the GM-CSF-sensitivity of hematopoietic progenitor cells but also, within a period of 12 weeks, almost completely reversed the morphologic features of surfactant accumulation. These results were obtained despite modest transduction levels (10-20%) and, in comparison to wild-type mice, clearly reduced βc expression levels were detected in hematopoietic cells. Therefore, our data demonstrating genetic and functional correction of mβc-/- deficiency in vitro as well as in a murine in vivo model of PAP strongly suggest gene therapy as a potential new treatment modality in βc-deficient PAP.
Abstract 5230: <i>In vivo</i> imaging of tumor malignancy with near-infrared fluorescence probes specific to HIF-active cells
Authors: Takahiro Kuchimaru, Tetsuya Kadonosono, Takashi Ushiki, Mark McDougall, Shinae Kizaka-Kondoh, Masahiro Hiraoka
Journal: Cancer Research (2010)

Abstract In solid tumors, the distribution of oxygen pressure is not homogenous because of the uncontrolled tumor growth and immature blood vessels during angiogenesis, which generate a hypoxic microenvironment. Tumor hypoxia causes resistance to radiotherapy and chemotherapy, and malignant progression Hypoxia-inducible factor-1 (HIF-1) is a master transcriptional regulator for adaptation to hypoxia by inducing more than 100 genes, which are closely associated with malignant phenotype. Thus, HIF-1-active cells are hallmark of malignant tumors. We have been developing fusion protein probes specific to HIF-1-active microenvironment for imaging and targeting malignant tumors. We recently constructed a fusion protein POH, which consisted of Protein Transduction Domain (PTD), Oxygen-dependent Degradation Domain (ODD) and HaloTag. The PTD was a membrane-permeable peptide, which efficiently delivered fusion proteins into cells. The ODD was responsible for the oxygen-dependent regulation of the probe, which stabilized in a hypoxic environment and degraded immediately under normoxic conditions. In addition, HaloTag was used to covalently conjugate with its specific ligand labeled with near-infrared fluorescence (NIRF) dye. POH-NIRF was examined for its target-specificity and in vivo dynamic status by in vivo and ex vivo fluorescence imaging with IVIS-SPECTRUM. To visualize the targets in vivo, we used bioluminescence imaging of tumor cells, which stably retained a HIF-1-dependent luciferase reporter gene. POH-NIRF probes successfully imaged HIF-1-active regions defined by bioluminescence imaging in subcutaneously implanted human xenograft tumors and orthotopic pancreatic cancers 9 to 24 hrs after POH-NIRF injection. Furthermore, immunohistochemical analysis of tumor sections from the mice 6h after POH-NIRF injection revealed the regions imaged with POH-NIFR was overlapped with HIF-1α-positive regions, while the intracellular localization of POH-NIRF was in cytoplasm. Overall results demonstrated that POH-NIRF was a specific probe for HIF-1-active/hypoxic cells and suggested that a PTD-ODD probe would become a unique imaging probe for tumor malignancy. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5230.
Cross-national Comparisons of Long-term Care Become a Gold Mine for Rigorous Investigators
Authors: Teri Randall
Journal: JAMA (1993)

A FEW YEARS ago, investigators from the United States and Japan teamed up to ask why nursing home residents in the United States had more hip fractures than their counterparts in Japan, despite their higher bone density. They hypothesized that elderly Japanese people fall less frequently because they have stronger quadriceps muscles owing to their custom of squatting to sleep on tatami mats or to use Japanese-style toilets. The researchers soon learned that quadriceps strength and gait characteristics were nearly identical in the two study groups. Yet during the 4-month study, only 10% of the Japanese nursing home residents had falls, compared with 37% of their American counterparts (<i>J Am Geriatr Soc</i>. 1991;39:A10). The researchers examined many other variables, including how much the residents are assisted with walking and dressing and the use of assisting devices. They were all essentially the same except for one: falls in the US cohort
Power Doppler signals after percutaneous ethanol injection therapy for hepatocellular carcinoma predict local recurrence of tumors: a prospective study using 199 consecutive patients
Authors: Shin'pei Sato, Yasushi Shiratori, Masatoshi Imamura, Takuma Teratani, Shun'taro Obi, Yukihiro Koike, Yasuo Imai, Haruhiko Yoshida, Shuichiro Shiina, Masao Omata
Journal: Journal of Hepatology (2001)
Identification of a Variant in <i>KDR</i> Associated with Serum VEGFR2 and Pharmacodynamics of Pazopanib
Authors: Michael L. Maitland, Chun-Fang Xu, Yu-Ching Cheng, Emily Kistner-Griffin, Kathleen A. Ryan, Theodore G. Karrison, Soma Das, Dara Torgerson, Eric R. Gamazon, Vasiliki Thomeas, Matthew R. Levine, Paul A. Wilson, Nan Bing, Yuan Liu, Lon R. Cardon, Lini N. Pandite, Jeffrey R. O'Connell, Nancy J. Cox, Braxton D. Mitchell, Mark J. Ratain, Alan R. Shuldiner
Journal: Clinical Cancer Research (2014)

Abstract Purpose: VEGF receptor (VEGFR) kinases are important drug targets in oncology that affect function of systemic endothelial cells. To discover genetic markers that affect VEGFR inhibitor pharmacodynamics, we performed a genome-wide association study of serum soluble vascular VEGFR2 concentrations [sVEGFR2], a pharmacodynamic biomarker for VEGFR2 inhibitors. Experimental Design: We conducted a genome-wide association study (GWAS) of [sVEGFR2] in 736 healthy Old Order Amish volunteers. Gene variants identified from the GWAS were genotyped serially in a cohort of 128 patients with advanced solid tumor with baseline [sVEGFR2] measurements, and in 121 patients with renal carcinoma with [sVEGFR2] measured before and during pazopanib therapy. Results: rs34231037 (C482R) in KDR, the gene encoding sVEGFR2 was found to be highly associated with [sVEGFR2], explaining 23% of the variance (P = 2.7 × 10−37). Association of rs34231037 with [sVEGFR2] was replicated in 128 patients with cancer with comparable effect size (P = 0.025). Furthermore, rs34231037 was a significant predictor of changes in [sVEGFR2] in response to pazopanib (P = 0.01). Conclusion: Our findings suggest that genome-wide analysis of phenotypes in healthy populations can expedite identification of candidate pharmacogenetic markers. Genotyping for germline variants in KDR may have clinical utility in identifying patients with cancer with unusual sensitivity to effects of VEGFR2 kinase inhibitors. Clin Cancer Res; 21(2); 365–72. ©2014 AACR.
1056-144 Multiexpert blinded interpretation of electrocardiogram-gated SPECT imaging in women: Relative performance of thallium-201 and technetium-99m sestamibi
Authors: Timothy M Bateman, Frans J.Th Wackers, Jennifer H Mieres, Kelly L Moutray, James A Case, Ginger J Hertenstein, John A House, S.James Cullom
Journal: Journal of the American College of Cardiology (2004)
Distinctive NK-cell receptor repertoires sustain high-level constitutive NK-cell activation in HIV-exposed uninfected individuals
Authors: Sophie Ravet, Daniel Scott-Algara, Elodie Bonnet, Hung Khiem Tran, Ton Tran, Ngai Nguyen, Lien Xuan Truong, Ioannis Theodorou, Françoise Barré-Sinoussi, Gianfranco Pancino, Pascale Paul
Journal: Blood (2007)
Suicidal Depression and Physical Illness
Authors: Jan Fawcett
Journal: JAMA (1972)

The association of suicide with active physical illness is high, and the possibility of suicide is increased when symptoms of clinical depression, such as loss of appetite, sleep disturbance, or feelings of hopelessness are present as well. Additional alerting factors are previous history of affective illness, previous suicidal behavior, and limited interpersonal resources. Patients should be queried about suicidal thoughts, since they will frequently admit to such with relief of anxiety. Measures for protection of the patient should be instituted immediately until psychiatric evaluation and care can be obtained. Explanations of the relationship of suicidal impulses to depressive illness and the communication of a realistic attitude of therapeutic optimism will help to diminish anxiety in the patient and his family.
Renal Damage after Acute Pyelonephritis
Authors: R. R. Bailey, P. J. Little, G. L. Rolleston
Journal: BMJ (1969)

Intravenous pyelograms done before, during, and after an attack of acute pyelonephritis in a 41-year-old woman showed an increase in the size of both kidneys during the attack. The right kidney did not excrete the contrast medium during the acute episode. When function returned it became smaller, and three months after the attack of pyelonephritis this kidney was 1 cm. shorter than before it.
Differential Protein Kinase C Isoform Abundance in Ascending Aortic Aneurysms From Patients With Bicuspid Versus Tricuspid Aortic Valves
Authors: Jeffrey A. Jones, Robert E. Stroud, Brooke S. Kaplan, Allyson M. Leone, Joseph E. Bavaria, Joseph H. Gorman, Robert C. Gorman, John S. Ikonomidis
Journal: Circulation (2007)

Background— It is recognized that different events contribute to the initiation of ascending thoracic aortic aneurysms (ATAAs) in patients with bicuspid aortic valves (BAV) versus patients with tricuspid aortic valves (TAV), but the molecular signaling pathways driving aneurysm formation remain unclear. Protein kinase C (PKC) is a superfamily of kinases which differentially mediate signaling events that lead to altered gene expression and cellular function, and may regulate downstream mediators of vascular remodeling. The present study tested the hypothesis that ATAA development in patients with BAV versus TAV proceeds by independent signaling pathways involving differential PKC signaling. Methods and Results— ATAA samples were collected from BAV (n=57) and TAV (n=55) patients and assessed for 10 different PKC isoforms by immunoblotting. Results were expressed as a percent change in abundance (mean±SEM) from a nonaneurysmal control group (100%, n=21). Correlation analysis was performed, and relationships between PKC and matrix metalloproteinase abundance were reported. In the BAV group, classic and novel PKC isoforms (PKC-α, βΙ, γ, ε, θ) were increased, whereas PKC-η and atypical PKC-ζ were decreased. In the TAV group, classic and novel isoforms were decreased and atypical PKC-ζ was elevated. Positive correlations between PKC and matrix metalloproteinase abundance were identified. Conclusions— Differential PKC isoform abundance was observed in ATAA samples from patients with BAV versus TAV, suggesting independent molecular signaling pathways may be operative. Induction of independent transcriptional programs may result and may provide a mechanistic foundation for developing selective diagnostic/therapeutic strategies for patients with ATAAs secondary to BAV or TAV.
Can stories of personal tragedy spark a healthcare revolution?
Authors: Janice Hopkins Tanne
Journal: BMJ (2006)

R emaking American Medicine is much more than a four-part television series. It is part of a continuing campaign to improve US healthcare, as described on its website. In the period leading up to the broadcasts, a national outreach campaign used healthcare providers and patient advocates to spread the word and maximise the television audience to a goal of around 100 million Americans.

Many of the improvements described in this series grew out of personal tragedies that led parents and partners to work for changes in the system rather than filing malpractice suits. The key message is that when it comes to remaking American medicine, patients are as important as health professionals.

The first programme, Silent Killer , is about medical errors—in this case the failure to notice a child's deteriorating condition. Sorrel King's 18 month old daughter died from dehydration at Johns Hopkins University Hospital, despite her parents' attempts to alert nurses and doctors to her deteriorating condition. Mrs King and her husband insisted that the hospital make changes, not …
Disparity between Solid-Organ Supply and Demand
Authors: Anthony J. Langone, J. Harold Helderman
Journal: New England Journal of Medicine (2003)

More patients die awaiting solid-organ transplantation than currently receive viable organs. Perhaps a victim of its own success, transplantation is the treatment of choice for failed organ function. Despite the burgeoning demand for transplanted organs, the number of available cadaveric organs has remained essentially static over the past decade. As a result, the waiting list for renal transplants in the United States has grown to more than 52,000 patients, with average waiting times exceeding 1000 days.In this issue of the Journal, Sheehy et al.1 tackle the critical issue of the shortage of cadaveric donors, attempt to ascertain where the . . .
Peritoneoscopy of Peliosis Hepatis
Authors: T. Ito
Journal: Endoscopy (1982)

Five cases of peliosis hepatis diagnosed by peritoneoscopy (two confirmed by liver biopsy) are presented. The patients were 4 males and one female, and their ages ranged from 31 to 43 years. Each patient had had an episode of jaundice with fever in the past. At peritoneoscopy, the lesions appeared as reddish-purple spots measuring up to 2.0 mm in diameter. These spots did not show protrusion or retraction, and had no clear relationship with the lobular markings formed by portal triads. In one case, spots were connected to form irregular meshworks in places. In other cases, spots were found or oblong. Histologically, a spot obtained with a punch biopsy forceps had dilated sinusoids filled with red blood cells. Similar dilated sinusoids were observed in deep tissues of the liver obtained with a Vim-Silverman needle. Reconstruction studies of a liver biopsy specimen proved that peliosis lesions were collections of dilated sinusoids. The lesions formed ellipsoids with an irregular margin and were located in the central and intermediate zones of a liver lobule. Other histological features of the liver, mainly observed in the central area were: central fibrosis, fatty metamorphosis, slight liver cell necrosis, and cholestasis. Peliosis hepatis in cases with acute hepatitis and chronic alcoholic liver injury as in the present series is a new finding. The lesion was also seen in a case of primary liver cancer.
1081-47 The benefit of coronary stenting in small vessels is dependent on reference vessel diameter: Results from a meta-analysis of 11 randomized trials
Authors: Raul Moreno, Cristina Fernandez, Rosana Hernandez-Antolin, Maria J Perez-Vizcayno, Fernando Alfonso, Javier Escaned, Manel Sabaté, Camino Bañuelos, Carlos Macaya
Journal: Journal of the American College of Cardiology (2004)
Narrative in Health Care: Healing Patients, Practitioners, Profession, and Community
Authors: David S. Riley
Journal: Annals of Internal Medicine (2009)

Medical Writings: Book Notes21 April 2009Narrative in Health Care: Healing Patients, Practitioners, Profession, and CommunityDavid S. Riley, MDDavid S. Riley, MDFrom the University of New Mexico Medical School, Santa Fe, New Mexico.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-150-8-200904210-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Engel JD, Zarconi J, Pethtel LL, Missimi SA. 270 pages. Oxford: Radcliffe Publishing; 2008. $49.95. ISBN 9781846191930. Order at www.radcliffe-oxford.com/books.Field of medicine: General medical practice.Format: Softcover book.Audience: This scholarly book is for health care providers who want to better understand the role of a patient's story and its meaning and role in the healing process.Purpose: To provide the skills necessary to practice narrative or relationship-centered medicine.Content: The narrative process is a way to bridge the gaps in our health care system that so often separate patients from practitioners. To meaningfully honor a patient's story requires ... Author, Article, and Disclosure InformationAffiliations: From the University of New Mexico Medical School, Santa Fe, New Mexico. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 April 2009Volume 150, Issue 8Page: 572KeywordsComaExerciseHealth careHealth care providersHealth information technologyPatientsSoftware tools ePublished: 21 April 2009 Issue Published: 21 April 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Medical care in Iraq after six years of sanctions
Authors: R. Garfield, S. Zaidi, J. Lennock
Journal: BMJ (1997)

In April 1996 we visited Iraq to assess medical care services six years after the United Nations imposed economic sanctions. We visited a range of hospitals and health centres, which included 20% of Iraq's civilian institutional beds, in all regions of the country, except the Kurdish Autonomous Region.

We found nearly one third of hospital beds were closed, and the average length of stay had more than halved since before the Gulf war. More than half of the hospitals' diagnostic and therapeutic equipment was not working owing to a lack of spare parts or maintenance. All public hospitals experienced serious problems with lighting, cleaning, water supply, and sewage. We found that patients routinely brought their own blankets for warmth and used personal kerosene or electric heaters. By contrast, the second floor of Baghdad's Ibn El Baladi Hospital got so hot in summer that “any child who comes to the hospital without a fever ends up with one.”

One hospital's cleaning budget was 1500 dinars a month (about £1.50 ($2) at black market rates), which provided only hand soap for operating theatres. Disinfectants and antiseptics were almost non-existent. Hospitals were cleaned only with water. At the Ibn Al Atheer Hospital pieces of sheets and blankets from beds had replaced brushes on electric …
Response to Letter Regarding Article, “Induced Brugada-Type Electrocardiogram, a Sign for Imminent Malignant Arrhythmias”
Authors: M. Juhani Juntilla, Heikki V. Huikuri, Begona Benito, Josep Brugada, Kevin Vernooy, Andrea Sarkozy, Pedro Brugada, Ramon Brugada
Journal: Circulation (2008)

Brugada-Type Electrocardiogram, a Sign for Imminent Malignant Arrhythmias"We* thank Drs Behr and Camm for their comments on our study. 1e could not agree more.Referral centers have a bias in their population because they will receive the most severe forms of a disease.Likewise, all disease registries, especially those dedicated to diseases with a low prevalence, have an intrinsic bias.It is highly likely that a patient who has had an adverse reaction will be more easily noticed and incorporated into a registry and that without the adverse reaction, the physician will miss the uncommon phenotype.Likewise, it is likely that those cases in which the physician feels he or she could have done better will not be sent to a registry.This is just human nature.Nevertheless, in medicine, we often use case reports as the proof of concept for the adoption of medical preventive guidelines, be it stopping exercise in some diseases or avoiding medications in individuals with certain genotypes.On the basis of minimal data, we discontinue first, and then we hope that time and further recruitment will prove or refute whether the association was correct.The present work was not meant to be a systematic or longitudinal study of medications that induce a Brugada ECG pattern.This is a collection of case reports of induced Brugada ECG pattern that we have received and evaluated and in which we show that half of the population presented with malignant arrhythmias.Considering that these are young individuals, most of whom were previously healthy, we think that this is of tremendous importance.We provide clear evidence, despite the bias, that the induction of the ECG pattern under an acute process or medication may be followed by the triggering of malignant arrhythmias.How common is this presentation?We do not know; monitoring is not always performed for the right precordial leads, and few noncardiac physicians are aware of what ST elevation in V 1 -V 2 means during anesthesia.In any case, we believe that this is not an ECG pattern that can be disregarded in an individual who presents with an acute process, because it can give you a big scare.That was the main message of our report.
THE DISADVANTAGES OF LOW PROTEIDS IN INFANT FEEDING.
Authors: ALFRED HAND
Journal: JAMA (1907)

if he would outline the differences, instead of saying they are different, which everybody knows.The same trend of thought is noticeable in his attitude toward paresis.Alcohol does not cause true paresis; alcoholic pseucfoparesis is another thing.This is true, but, continued Dr. Jelliffe, what we want to know, and what a number of students have been trying to tell us is, how are we, from a clinical point of view, going to decide in the small number of cases where a differential is necessary?
Commentary: Becoming a person centred practice
Authors: Farhan Amin
Journal: BMJ (2015)

Providing patients with access to their medical records can improve their communication with clinicians and increase their understanding of their illness. It’s therefore baffling that only 3% of people in the UK have online access to them.1 This should increase given NHS England’s pledge to give patients full access to their medical records by 2018.

The concerns Walker et al summarise about opening notes to patients2 were echoed in our practice two years ago, before we decided to offer patients full online access to their records. Concerns centred on …