tbuckley/cabot-search huggingface dataset:
Localized Gene Expression Following Administration of Adeno-associated Viral Vectors via Pancreatic Ducts
Authors: Scott A. Loiler, Qiushi Tang, Tracy Clarke, Martha L. Campbell-Thompson, Vince Chiodo, William Hauswirth, Pedro Cruz, Marcel Perret-Gentil, Mark A. Atkinson, Vijayakumar K. Ramiya, Terence R. Flotte
Journal: Molecular Therapy (2005)

Gene transfer into pancreatic cells in vivo could be of immense therapeutic benefit in cases of type 1 diabetes (T1D) through the production of molecules capable of interrupting the progression of autoimmunity or promoting regeneration of insulin-secreting beta cells. We adapted a clinically relevant surgical technique (endoscopic retrograde cholangiopancreatography) to deliver rAAV encoding human alpha1-antitrypsin (approved gene symbol SERPINA1) to the pancreas of 3-week-old Fisher 344 rats and C57BL/6 mice. We compared natural as well as bioengineered serotypes of rAAV (rAAV1, rAAV2/Apo, rAAV8) as well as different promoters (chicken beta-actin, human insulin) for their expression in vivo. Rats injected with rAAV1 showed the highest hAAT expression (week 2, rAAV1/CB-AT, 579 +/- 457 ng/ml). In mice, rAAV8 vector delivered the highest serum concentration of hAAT (week 2, rAAV8/CB-AT, 19 +/- 6 microg/ml). The chicken beta-actin promoter provided the highest expression in both rodent experiments. Immunohistochemical staining indicated transduction primarily of pancreatic acinar cells with either the rAAV1/CB-AT vector in the rat or the rAAV8/CB-AT vector in the mouse. This study demonstrates that rAAV vectors can be designed to deliver therapeutic genes efficiently to the pancreas and achieve high levels of gene expression and may be useful in treating pancreatic disorders, including T1D.
Aortic Disease in Marfan's Syndrome
Authors: Richard B. Devereux, Mary J. Roman
Journal: New England Journal of Medicine (1999)

For most of the century after Marfan first described the skeletal features of the condition that bears his name,1 progress with regard to Marfan's syndrome was marked by incremental increases in the understanding of its skeletal, ocular, and cardiovascular features but no reduction in its toll of premature death. Most deaths were due to dissection or rupture of the aorta or to heart failure resulting from severe aortic regurgitation. In 1972, the median life expectancy of patients with Marfan's syndrome was reported to be about 45 years,2 with women surviving approximately 10 years longer than men. Beginning around that time, . . .
Treatment of Raynaud's phenomenon by intravenous infusion of prostacyclin (PGI2)
Authors: PAULINE M. DOWD, M.F.R. MARTIN, E.D. COOKE, SALLY A. BOWCOCK, R. JONES, P.A. DIEPPE, J.D.T. KIRBY
Journal: British Journal of Dermatology (1982)

Twenty five patients with Raynaud's phenomenon due to systemic sclerosis were infused with prostacyclin (PGI2). In 88% of the patients there was objective improvement, monitored by thermography or radiometry.
POLIOMYELITIS BY ACCIDENTAL CONTAGION IN THE CHIMPANZEE
Authors: Howard A. Howe, David Bodian
Journal: The Journal of Experimental Medicine (1944)

Poliomyelitis virus was isolated from the stools of two uninoculated chimpanzees which had been quartered for 6 months in cages adjoining those of rhesus monkeys receiving intranasal inoculations of potent human stools. Upon arrival, and for 4 months thereafter, neither chimpanzee had antibody against the virus eventually isolated from it. However, antibody had developed against the animals' own virus strains at the time these were isolated from the feces.
DIAGNOSTIC CRITERIA OF MALIGNANT DISEASE IN THE UPPER RIGHT QUADRANT
Authors: M. L. GRAVES
Journal: JAMA (1926)

The abdomen contains no less than thirty-seven important organs and tissues, if we include the adjacent retroperitoneum, and every one of these is subject to malignant disease. The variety and complexity of these organs and resulting clinical phenomena in malignant disease are so intriguing that careful clinicians must take keen delight in every research that advances conclusive diagnosis. The upper right quadrant, the limitation of my paper, embraces no less than twelve of these organs, and is the most interesting and difficult of the abdominal divisions. <h3>CLINICAL PHENOMENA</h3> The number, variety and functional activities of these organs in malignant diseases will produce such alterations in the anatomy, usually progressive destruction, as may often be recognized; if physiologic alterations in secretion and excretion and absorption and motor function could be as easily recognized at early stages, much improvement in diagnosis and even in treatment would result. Subjective phenomena are still of
SIECUS and Sex Education
Authors: Harold I. Lief
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Several of the 13 letters (<b>209</b>:940, 1969) dealing with sex education in schools attacked the Sex Information and Education Council of the United States (SIECUS): There are Communists and Communist organizations working in and with SIECUS. What is proposed by SIECUS is not sex education but is an attempt to change conventional attitudes toward sex. The teaching materials proposed for use in the nation's schools do not conform with any ever before considered suitable for children. The allegation that SIECUS is part of a Communist conspiracy to undermine the morality of our children is a John Birch and Christian Crusade piece of propaganda. Sprague H. Gardiner in his letter pointed out how easy it is "for prejudiced individuals and groups to find a scapegoat which they identify as the cause of all our troubles." Ironically, behind the iron curtain Communists have stated repeatedly that sex education
Pneumococcal Serotypes and Mortality following Invasive Pneumococcal Disease: A Population-Based Cohort Study
Authors: Zitta B. Harboe, Reimar W. Thomsen, Anders Riis, Palle Valentiner-Branth, Jens Jørgen Christensen, Lotte Lambertsen, Karen A. Krogfelt, Helle B. Konradsen, Thomas L. Benfield
Journal: PLoS Medicine (2009)

Pneumococcal disease is a leading cause of morbidity and mortality worldwide. The aim of this study was to investigate the association between specific pneumococcal serotypes and mortality from invasive pneumococcal disease (IPD).In a nationwide population-based cohort study of IPD in Denmark during 1977-2007, 30-d mortality associated with pneumococcal serotypes was examined by multivariate logistic regression analysis after controlling for potential confounders. A total of 18,858 IPD patients were included. Overall 30-d mortality was 18%, and 3% in children younger than age 5 y. Age, male sex, meningitis, high comorbidity level, alcoholism, and early decade of diagnosis were significantly associated with mortality. Among individuals aged 5 y and older, serotypes 31, 11A, 35F, 17F, 3, 16F, 19F, 15B, and 10A were associated with highly increased mortality as compared with serotype 1 (all: adjusted odds ratio >or=3, p<0.001). In children younger than 5 y, associations between serotypes and mortality were different than in adults but statistical precision was limited because of low overall childhood-related mortality.Specific pneumococcal serotypes strongly and independently affect IPD associated mortality.
Mucociliary clearance in patients with chronic autonomic failure.
Authors: P Jenkins, D Pavia, J R Bateman, S W Clarke, K M Citron, R Bannister
Journal: Thorax (1980)

Mucociliary clearance was measured in four patients with chronic autonomic failure and normal ventilatory function using a method of scanning the clearance of inhaled polystyrene particles tagged with 99mTc. Previous surgical and experimental evidence has suggested that autonomic denervation might be expected to impair clearance. However, the four patients in this study showed no significant difference in clearance rate compared to groups of sex-matched control subjects. A fifth patient was found to have impaired mucociliary clearance. However she had the symptoms and ventilatory function of smoking-related chronic obstructive bronchitis, a condition which has previously been shown to impair mucociliary clearance.
Separation of antigen-specific lymphocytes. II. Enrichment of hapten-specific antibody-forming cell precursors.
Authors: W Haas
Journal: The Journal of Experimental Medicine (1975)

Normal spleen cells were separated in dishes coated with thin layers of DNP-gelatin or NIP-gelatin into binding and nonbinding cells and stimulated in vitro with DNP- and/or NIP-conjugated polymerized flagellin (POL). Hapten-specific unresponsiveness was induced in the binding cell population by melting the gel at 37 degrees C or in unfractionated cells by pretreatment with soluble hapten-gelatin and could be reversed by treatment with collagenase. A specific enrichment of anti-DNP and anti-NIP antibody-forming cell precursors (AFCP) could be demonstrated in the binding cell populations after treatment with collagenase in cultures with or without "feeder" cells. However, the response of small numbers of unfractionated and purified hapten-specific spleen cells was suboptimal even in the presence of mitomycin-treated or irradiated feeder cells. Optimal numbers of anti-DNP (anti-NIP) antibody-forming cells were generated by small numbers of normal or purified spleen cells in the presence of spleen cells depleted of anti-DNP (anti-NIP) AFCP. In this system the response of only 2 times 10-4 purified hapten-specific cells was higher than the response of 10-6 unfractionated cells. Purified DNP-specific cells responded only to DNP-POL but not to NIP-POL and purified NIP-specific cells responded only to NIP-POL but not to DNP-POL. The degree of enrichment of anti-DNP AFCP decreased with increasing numbers of binding cells. NIP3-gelatin layers bound four to five times less spleen cells than DNP2-gelatin layers and the enrichment of anti-NIP AFCP (about 300-fold) was three times greater than the enrichment of anti-DNP AFCP (about 100-fold). The immunological significance of hapten-gelatin binding cells which apparently failed to respond to antigen is discussed.
Withdrawal From Benzodiazepines
Authors: Scott D. Jones
Journal: JAMA (1984)

<h3>To the Editor.—</h3> I read with interest the recent report inThe Journalby Conell and Berlin<sup>1</sup>on withdrawal reactions associated with chronic benzodiazepine use and wish to make the following comments. While the routine monitoring of blood levels of benzodiazepines is not warranted, I believe that when a patient has a history of chronic intake of a benzodiazepine<i>plus</i>a history of symptoms suggesting a withdrawal state<i>or</i>overuse of medication, ie, restlessness, difficulty concentrating, or irritability, obtaining a benzodiazepine level may be helpful in the clinical treatment of the patient. I recently treated a patient with a similar history as the first case in Conell and Berlin's report. The patient had been taking clorazepate from her physician for more than four years but had initially minimized her dosage and the duration of ingestion of it. A blood level determination helped solve the perplexing clinical state of my
Quantitative features in the computed tomography of healthy lungs.
Authors: B H Fromson, D M Denison
Journal: Thorax (1988)

This study set out to determine whether quantitative features of lung computed tomography scans could be identified that would lead to a tightly defined normal range for use in assessing patients. Fourteen normal subjects with apparently healthy lungs were studied. A technique was developed for rapid and automatic extraction of lung field data from the computed tomography scans. The Hounsfield unit histograms were constructed and, when normalised for predicted lung volumes, shown to be consistent in shape for all the subjects. A three dimensional presentation of the data in the form of a "net plot" was devised, and from this a logarithmic relationship between the area of each lung slice and its mean density was derived (r = 0.9, n = 545, p less than 0.0001). The residual density, calculated as the difference between measured density and density predicted from the relationship with area, was shown to be normally distributed with a mean of 0 and a standard deviation of 25 Hounsfield units (chi 2 test: p less than 0.05). A presentation combining this residual density with the net plot is described.
Diabetic Polyneuropathy: The Importance of Insulin Deficiency, Hyperglycemia and Alterations in Myoinositol Metabolism in Its Pathogenesis
Authors: Howard L. Bleich, Emily S. Boro, Albert I. Winegrad, Douglas A. Greene
Journal: New England Journal of Medicine (1976)

The diabetic neuropathies include a variety of syndromes that differ in their clinical manifestations, prognoses and, in some instances, their pathologic bases. Distal symmetrical polyneuropathy, the most common form of diabetic neuropathy, is a major cause of morbidity in diabetic persons and can have a primary role in the development of foot ulcers. At present, there is no effective means for prevention or treatment of diabetic polyneuropathy, and its pathogenesis is unknown. Neuropathological studies have excluded occlusive arterial disease and diabetic "microangiography" as major factors, and most workers now believe that the development of this syndrome is conditioned by some . . .
IL-2– and IL-15–induced activation of the rapamycin-sensitive mTORC1 pathway in malignant CD4+ T lymphocytes
Authors: Michal Marzec, Xiaobin Liu, Monika Kasprzycka, Agnieszka Witkiewicz, Puthiyaveettil N. Raghunath, Mouna El-Salem, Erle Robertson, Niels Odum, Mariusz A. Wasik
Journal: Blood (2007)
Portal hypertension in schistosomiasis: A long-term follow-up of a randomized trial comparing three types of surgery
Authors: Silvano Raia, Luiz Caetano Da Silva, Luiz Carlos C. Gayotto, Sonia Coutinho Forster, Julia Fukushima, Edna Strauss
Journal: Hepatology (1994)

The long-term follow-up of patients with the severe form of Manson's schistosomiasis who had had elective surgical treatment for portal hypertension, in a randomized trial, was clinically evaluated. Of 94 patients, proximal splenorenal shunting was performed in 32, esophagogastric devascularization with splenectomy in 32 and distal splenorenal shunting in 30. Patients were observed during a mean of 85.7 +/- 33.1 mo, excluding nine patients (9.6%) who were lost to follow-up. Recurrence of upper gastrointestinal tract bleeding occurred in 24.1% of the patients, without statistical differences among the three groups, but rebleeding because of varices was more frequent after esophagogastric devascularization with splenectomy. Hepatic encephalopathy was significantly higher after proximal splenorenal shunting (39.3%) when compared with distal splenorenal shunting (14.8%) and with esophagogastric devascularization with splenectomy (0%). Lethality was also significantly higher after proximal splenorenal shunting (42.9%) when compared with distal splenorenal shunting (14.8%) and with esophagogastric devascularization with splenectomy (7.1%). Indirect hyperbilirubinemia was absent after esophagogastric devascularization with splenectomy and more frequent after distal splenorenal shunting (52%) although also present after proximal splenorenal shunting (29.6%). Esophagogastric devascularization with splenectomy was demonstrated to be the best option because of the absence of encephalopathy and because of low mortality rates. Hepatic encephalopathy occurred after distal splenorenal shunting but in a lesser percentage than after proximal splenorenal shunting. The higher incidence of encephalopathy and lethality proscribes proximal splenorenal shunting in Manson'schistosomiasis.
NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors
Authors: Joshua D. Hawk, Angie L. Bookout, Shane G. Poplawski, Morgan Bridi, Allison J. Rao, Michael E. Sulewski, Brian T. Kroener, David J. Manglesdorf, Ted Abel
Journal: Journal of Clinical Investigation (2012)

The formation of a long-lasting memory requires a transcription-dependent consolidation period that converts a short-term memory into a long-term memory. Nuclear receptors compose a class of transcription factors that regulate diverse biological processes, and several nuclear receptors have been implicated in memory formation. Here, we examined the potential contribution of nuclear receptors to memory consolidation by measuring the expression of all 49 murine nuclear receptors after learning. We identified 13 nuclear receptors with increased expression after learning, including all 3 members of the Nr4a subfamily. These CREB-regulated Nr4a genes encode ligand-independent “orphan” nuclear receptors. We found that blocking NR4A activity in memory-supporting brain regions impaired long-term memory but did not impact short-term memory in mice. Further, expression of Nr4a genes increased following the memory-enhancing effects of histone deacetylase (HDAC) inhibitors. Blocking NR4A signaling interfered with the ability of HDAC inhibitors to enhance memory. These results demonstrate that the Nr4a gene family contributes to memory formation and is a promising target for improving cognitive function.
Tolerance to the humoral and hemodynamic effects of caffeine in man.
Authors: D Robertson, D Wade, R Workman, R L Woosley, J A Oates
Journal: Journal of Clinical Investigation (1981)

Acute caffeine in subjects who do not normally ingest methylxanthines leads to increases in blood pressure, heart rate, plasma epinephrine, plasma norepinephrine, plasma renin activity, and urinary catecholamines. Using a double-blind design, the effects of chronic caffeine administration on these same variables were assessed. Near complete tolerance, in terms of both humoral and hemodynamic variables, developed over the first 1-4 d of caffeine. No long-term effects of caffeine on blood pressure, heart rate, plasma renin activity, plasma catecholamines, or urinary catecholamines could be demonstrated. Discontinuation of caffeine ingestion after 7 d of administration did not result in a detectable withdrawal phenomenon relating to any of the variables assessed.
Abstract 4900: Functional and mechanism analysis of LGR4 in human lung cancer cells.
Authors: Xing Gong, Wei Xiong, Jing Yi, Kendra S. Carmon, Qingyun Liu
Journal: Cancer Research (2013)

Abstract LGR4 (leucine-rich repeat containing G protein-coupled receptor 4) and its two closely related homologues LGR5 and LGR6 (LGR4-6) are members of the seven transmembrane domain (7TM) receptors with critical functions in embryonic development and adult stem cells. Recently, we and others discovered that LGR4-6 function as receptors of R-spondins (RSPO) to potentiate Wnt signaling. RSPOs are a group of four secreted proteins (RSPO1-4) with essential roles in organ development, sex determination, carcinogenesis, etc. Particularly, RSPO2 is required for normal lung development through enhancement of Wnt signaling and LGR6 is expressed in adult lung stem cells in the mouse. Among the 900 or so 7TM receptors, LGR4 was found to be one of the few that were highly upregulated in both squamous cell carcinoma (SqCC) and adenocarcinoma (AC) of the lung. Alterations in the Wnt signaling pathways were found in a small percentage of lung cancer. Concurrent activation of β-catenin signaling enhances tumor growth and metastasis of lung cancer cells with KRAS mutation. Furthermore, RSPO3 and LGR4 are co-expressed at high levels in ∼20% of lung cancer cell lines. However, potential roles of RSPO3-LGR4 in lung carcinogenesis have not been investigated. We developed and validated a panel of LGR4 antibodies that can detect either native or denatured LGR4 with high specificity and sensitivity. Immunohistochemistry analyses confirmed that LGR4 was highly expressed in the majority of SqCC and AC of the lung. Knockdown of LGR4 in a lung cancer cell line with high levels of and LGR4 and RSPO3 leads to dramatic decrease in endogenous Wnt signaling and significant reduction in cell growth, migration, and colony formation in vitro. The effect of knockdown on tumor growth in vivo is being tested. Data from these expression and functional analyses of LGR4 in human lung cancer will be presented and discussed. Citation Format: Xing Gong, Wei Xiong, Jing Yi, Kendra S. Carmon, Qingyun Liu. Functional and mechanism analysis of LGR4 in human lung cancer cells. [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 4900. doi:10.1158/1538-7445.AM2013-4900
Advanced Dermatologic Therapy
Authors: Marie-Louise Johnson
Journal: JAMA (1987)

The Drs Shelley have presented us with a scholarly, appealing tome on the treatment of skin disease. It is reassuringly extensive, yet refreshingly concise, and presents a rare, over-the-shoulder glimpse of how a master of the specialty practices the art. The book is for those who are confident in their dermatologic diagnosis; it is not for the neophyte and makes no pretense of teaching materia dermatologica. Diagnoses tabulated alphabetically facilitate retrieval without consulting the index. In a most readable, literary approach to the intricacies and psychological overlay of the diagnosis, each is presented in a few paragraphs: what is known and unknown about the problem, the medical assessments that may be indicated, and the pitfalls that should be avoided. Then follows a succinct, annotated bibliography that culls from the literature recommended therapies, what might rightfully be anticipated from them, and their limitations. These bibliographies give flesh and breath to the
Colonoscopy with the Aid of a Steel Wire to Stiffen the Fiberscope
Authors: N. Gabrielsson, S. Granqvist, H. Ohlsén
Journal: Endoscopy (1972)

The steel wire was of great help for the insertion of the colonoscope. The percentage of complete examinations of the colon increased from 42 to 96 with this aid. Greater experience on the part of the examiner explained only a small part of this improvement. The most important technical difficulties in colonoscopy seem to have been solved.
Candida folliculitis associated with hypothyroidism
Authors: S. Dekio, C. Imaoka, J. Jidoi
Journal: British Journal of Dermatology (1987)

Journal Article Candida folliculitis associated with hypothyroidism Get access S. Dekio, S. Dekio Department of Dermatology, Shimane Medical University, 89–1 Enya‐cho, Izumo 693, Japan Search for other works by this author on: Oxford Academic Google Scholar C. Imaoka, C. Imaoka Department of Dermatology, Shimane Medical University, 89–1 Enya‐cho, Izumo 693, Japan Search for other works by this author on: Oxford Academic Google Scholar J. Jidoi J. Jidoi Department of Dermatology, Shimane Medical University, 89–1 Enya‐cho, Izumo 693, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue 5, 1 November 1987, Pages 663–664, https://doi.org/10.1111/j.1365-2133.1987.tb07501.x Published: 01 November 1987
Frailty is Independently Associated with Short Term Mortality and Hospitalization Due Heart Failure in the Elderly
Authors: Ali Deniz, Çağlar Özmen, İlayda Gül Berk, Ertuğrul Bayram, Vildan Yüksekdağ, Onur Sinan Deveci, Emre Çağlar Çağlıyan, Rabia Eker Akıllı, Mehmet Kanadaşı, Mesut Demir, Ayhan Usal, Mustafa Demirtaş, Gülşah Seydaoğlu
Journal: Journal of the American College of Cardiology (2013)
Experimental Goodpasture's syndrome in Wistar-Kyoto rats immunized with α3 chain of type IV collagen
Authors: Mauro Abbate, Raghuram Kalluri, Daniela Corna, Naoto Yamaguchi, Robert T. McCluskey, Billy G. Hudson, Giuseppe Andres, Carla Zoja, Giuseppe Remuzzi
Journal: Kidney International (1998)