tbuckley/cabot-search huggingface dataset:
Delivery and Protection of Adenoviruses Using Biocompatible Hydrogels for Localized Gene Therapy
Authors: Rachel Maddox Schek, Scott J Hollister, Paul H Krebsbach
Journal: Molecular Therapy (2003)

Localized gene delivery for repair of bone defects requires appropriate carriers for the gene therapy vectors. The objective of this study was to determine if hydrogels can control temporal and spatial delivery of adenovirus for localized gene therapy. Adenovirus expressing β-galactosidase was suspended in liquid or fibrin or collagen gels of varied concentrations and incubated prior to testing its bioactivity. The bioactivity of the virus was determined by exposing fibroblasts to the medium, the gels, or the elution medium from the gels. Bioactivity of adenovirus suspended in medium or collagen decreased to half-maximal activity after 15 h of incubation. In contrast, virus suspended in fibrin exhibited a threefold extension of bioactivity and did not reach half-maximal activity for 45 h. Bioactivity of adenovirus in hydrogels was determined to be a function of the gel concentration. In vivo experiments involved intramuscular implantation of BMP-7-expressing adenovirus in collagen, fibrin, or liquid in nude mice for 1, 2, or 4 weeks. Bone formation was observed only after 4 weeks, with bone formation occurring in 80% of muscles implanted with fibrin or collagen and 50% of muscles implanted with liquid. Fibrin gel also led to significantly larger ossicles, indicating that fibrin may offer protection from loss of infectivity both in vivo and in vitro. These results demonstrated that hydrogels may be used as carriers to control delivery of the virus and resultant tissue regeneration.
Contralateral renal artery fibromuscular dysplasia after nephrectomy for renal artery stenosis.
Authors: E O Jones, R Wilkinson, R M Taylor
Journal: BMJ (1978)

cortisol concentration was 3174 nmol/l (115 fg/100 ml) at 9 am and 2981 nmoljl (108 KLg/100 ml) at midnight, while there was no suppression after giving 8 mg dexamethasone.Bronchoscopy showed a tumour of the left upper lobe bronchus.His condition rapidly deteriorated, and he died six weeks after admission.Necropsy showed an oat cell carcinoma of the left upper lobe bronchus with widespread metastasis.Both adrenals were twice normal size because of diffuse cortical hyperplasia.The pituitary was normal.There was no evidence of lymphoma, leukaemia, or myeloma. DiscussionIn idiopathic late-onset immunoglobin deficiency there is usually an interval of several years before the malignancy develops,2 whereas in this patient both conditions presented together.Agammaglobulinaemia may complicate lymphoma, chronic lymphatic leukaemia, and myeloma but is not a feature of other malignancies.The exact relation- ship, if any, between the malignancy and the immune deficiency in this patient therefore remains obscure.Since side effects from corticosteroids are so common it was assumed at first that they were partly responsible for both his oedema and hypokalaemia.In retrospect clearly this was not so: the severity of the metabolic upset was out of keeping with the 7-mg dose of prednisolone he was receiving.The biochemical and histological changes were typical of ectopic ACTH-production, as was his rapid deterioration.3It is important to remember that, although drugs may cause many diseases, in each case alternative aetiologies should also be considered.
Carer and keeper
Authors: Joanna Bourke
Journal: The Lancet (2009)

The brain is a dazzling organ and one that most of us take for granted—that is, until something goes wrong. And when that "something" is Alzheimer's disease, its omnipotent role in determining "personhood" is exposed. According to Alzheimer's Disease International's 2009 World Alzheimer Report, about 35·6 million people worldwide will be living with Alzheimer's disease or other dementia in 2010. Many of those with Alzheimer's will be cared for by family members, as well as by trained volunteers and nurses, who struggle hourly (indeed, often, on a minute-by-minute basis) to care for these very sick people.
Cannabinoid Receptor Type 1 Protects against Age- Related Osteoporosis by Regulating Osteoblast and Adipocyte Differentiation in Marrow Stromal Cells
Authors: Aymen I. Idris, Antonia Sophocleous, Euphemie Landao-Bassonga, Meritxell Canals, Graeme Milligan, David Baker, Robert J. van't Hof, Stuart H. Ralston
Journal: Cell Metabolism (2009)
Microsporosis of the Scalp
Authors: Bernard Appel, Mauray J. Tye, William Halpern, Domenica Paci
Journal: New England Journal of Medicine (1951)

By COMPARISON with other large cities, Boston has not had the high incidence of tinea capitis prevalent in most of the country.1 , 2 It has, however, experienced a rapidly increasing incidence of infection with the human type of ringworm of the scalp, Microsporum audouini, as compared with the correspondingly diminished prevalence of the cat and dog type (zoophilic), Microsporum canis. This changing picture is a matter of growing concern because of the already widely recognized greater resistance and longer persistence of infection with the human type, M. audouini.Therefore, any new antifungoid preparation that promises superiority is avidly . . .
Hyponatremia During Adrenocorticotropin (ACTH) Infusions
Authors: GERHARD BAUMANN
Journal: Annals of Internal Medicine (1979)

Letters1 September 1979Hyponatremia During Adrenocorticotropin (ACTH) InfusionsGERHARD BAUMANN, M.D.GERHARD BAUMANN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-91-3-499_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the May 1979 issue Drs. Sheeler and Schumacher (1) report the cases of three patients who developed severe and symptomatic hyponatremia during prolonged (48-h) adrenocorticotropin (ACTH) tests. As pointed out by the authors, this problem was already recognized in the original report that introduced the 48-h ACTH test (2). Potential explanations for this complication offered by Sheeler and Schumacher are the known inability to excrete a water load in the patient with Addison's disease; and contamination of ACTH preparations with antidiuretic hormone (ADH). Water retention in hypoadrenal patients is due to glucocorticoid deficiency and can be...References1. SHEELERSCHUMACHER LO. Hyponatremia during ACTH infusions. Ann Intern Med. 1979;90:798-9. LinkGoogle Scholar2. ROSEWILLIAMSJAGGERLAULER LGPD. The 48-hour adrenocorticotrophin infusion test for adrenocortical insufficiency. Ann Intern Med. 1970;73:49-54. LinkGoogle Scholar3. BAUMANNRAYFIELDROSEWILLIAMSDINGMAN GELGJ. "Trace" contamination of corticotropin and human growth hormone with vasopressin: clinical significance. J Clin Endocrinol Metab. 1972;34:801-4. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Northwestern University Medical School Chicago, IL 60611 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited BySerum electrolyte abnormalities caused by drugs 1 September 1979Volume 91, Issue 3Page: 499-499KeywordsAdrenocorticotropic hormoneAntidiuretic hormoneHyponatremia Issue Published: 1 September 1979 PDF DownloadLoading ...
Nail in the heart no match for rural medical resources
Authors: Elizabeth Rasche González
Journal: JAMA (1980)

These days Bob Edwards, MD, spends most of his time at home in Telluride, Colo, finishing up his first novel. Recently he looked out the window and was startled to see a 30-year-old carpenter of his acquaintance ride by on a bicycle. Just six weeks previously, Edwards—who is a family practitioner—had been busy pouring lactated Ringer's solution into the carpenter as he lay in Telluride's Mountain Medical Center with a nail lodged in his heart. At the time, the patient was in hemorrhagic shock, with electromechanical dissociation, cardiac tamponade, and no detectable pulse or blood pressure (BP). But "he must have been getting a little circulation," Edwards told<i>JAMA</i>MEDICAL NEWS. It seems that the carpenter had been using a nail-driving gun and had accidentally shot a nail into his own chest, nailing, his heart to his sternum. The head of the nail was sticking out of the breastbone, and
Observational Studies of Drugs and Mortality
Authors: Wayne A. Ray
Journal: New England Journal of Medicine (2005)

Randomized controlled trials of therapies for the primary and secondary prevention of cardiovascular disease increasingly are powered to study overall mortality. The interventions frequently treat asymptomatic risk factors among high-risk patients and have a diverse spectrum of potential adverse effects. Thus, medications such as clofibrate or encainide that successfully alter surrogate end points but increase the rate of death are of little clinical interest. Many believe that a new preventive therapy for cardiovascular disease should be used sparingly, if at all, until clinical trials establish equivalence or even superiority to existing treatments in terms of mortality from all causes.When . . .
α<sub>4</sub>Integrins as Therapeutic Targets in Autoimmune Disease
Authors: Ulrich H. von Andrian, Britta Engelhardt
Journal: New England Journal of Medicine (2003)

In this issue of the Journal, two groups of investigators report on clinical trials of natalizumab, a recombinant monoclonal antibody against α4 integrins, for the treatment of multiple sclerosis1 and Crohn's disease.2 Miller et al. report that a group of patients with multiple sclerosis who received monthly injections of natalizumab had significantly fewer new inflammatory central nervous system lesions than the placebo group (a reduction of approximately 90 percent) and had approximately half as many clinical relapses.1 Ghosh et al. report that patients with Crohn's disease also had an improved response to natalizumab,2 with response and remission rates that . . .
Gilbert's disease and atazanavir: From phenotype to UDP-glucuronosyltransferase haplotype
Authors: Tim O. Lankisch, Ulrike Moebius, Michael Wehmeier, Georg Behrens, Michael P. Manns, Reinhold E. Schmidt, Christian P. Strassburg
Journal: Hepatology (2006)

Gilbert's disease leads to intermittent non-hemolytic hyperbilirubinemia by a reduction of hepatic bilirubin glucuronidation associated with the presence of the UDP-glucuronosyltransferase (UGT) 1A1*28 polymorphism. It is considered benign because it does not result in hepatocellular damage. However, pharmacogenetic analyses have linked UGT1A1*28 to drug toxicity and cancer predisposition. The protease inhibitor atazanavir (ATV) is an inhibitor of hepatic UGT activity leading to hyperbilirubinemia in individual patients. Whether this is linked specifically to UGT1A1*28 or to more complex variants influencing glucuronidation is unclear. One hundred and six ATV-treated patients were characterized and genotyped for UGT1A1*28, the UGT1A3 (-66C) and UGT1A7 (-57G) promoter variants, and UGT1A7129K/131K. ATV treatment increased median bilirubin levels from 10 to 41 μmol/L ( P = .001) with hyperbilirubinemia exceeding 43 μmol/L in 37%. Hyperbilirubinemia over 43 μmol/L was significantly associated not only with UGT1A1*28 but also with UGT1A3-66C, UGT1A7-57G, and UGT1A7129K/131K, although these variants do not naturally occur in linkage dysequilibrium in blood donors. Homozygous combinations of UGT1A1*28 with the other variants increased from 7.4% (normal bilirubin to 42 μmol/L) to 41% to 46.1% (43 to &gt;85 μmol/L), and 100% (&gt;85 μmol/L). All six patients with hyperbilirubinemia greater than 85 μmol/L were homozygous for all four variants identifying a haplotype inherited on a single allele. In conclusion , the genetic variant associated with Gilbert's disease is identified as part of a haplotype of four UGT1A variants spanning three genes at the UGT1A gene locus. This haplotype predisposes to hyperbilirubinemia in ATV treatment and may have an additional role as a pharmacogenomic risk factor for drug therapy.
Origins of New Male Germ-line Functions from X-Derived Autosomal Retrogenes in the Mouse
Authors: Meng-Shin Shiao, Pavel Khil, R. Daniel Camerini-Otero, Toshihiko Shiroishi, Kazuo Moriwaki, Hon-Tsen Yu, Manyuan Long
Journal: Molecular Biology and Evolution (2007)

Recent literature demonstrates that retrogenes tend to leave the X chromosome and integrate onto the autosomes and evolve male-biased expression patterns. Several selection-based evolutionary mechanisms have been proposed to explain this observation. Testing these selection-based models requires examining the evolutionary history and functional properties of new retrogenes, particularly those that show evidence of directional movement between the X and the autosomes (X-related retrogenes). This includes autosomal retrogenes with parental paralogs on the X chromosome (X-derived autosomal retrogenes) and those retrogenes integrated onto the X chromosomes (X-linked retrogenes). In order to understand why retrogenes tend to move nonrandomly in genomes, we examined the expression patterns and evolutionary mechanisms concerning gene pairs having young retrogenes—originating less than 20 MYA (after mouse–rat split). We demonstrate that these X-derived autosomal retrogenes evolved a more restricted male-biased expression pattern: they are expressed exclusively or predominantly in the testis, in particular, during the late stages of spermatogenesis. In contrast, the parental counterparts have relatively broad expression patterns in various tissues and spermatogenetic stages. We further observed that positive selection is targeting these X-derived autosomal retrogenes with novel male-biased expression patterns. This suggests that such retrogenes evolved new male germ-line functions that may be complementary to the functions of the parental paralogs, which themselves contribute little during spermatogenesis. Such evolutionary changes may be beneficial to the populations. Furthermore, most identified X-related retrogenes have recruited novel adjacent sequences as their untranslated regions (UTRs), suggesting that these UTRs, acquired de novo, may play an important role in establishing new regulatory mechanisms to carry out the new male germ-line functions.
1065 TARGETED THERAPY FOR LIVER CIRRHOSIS USING HYALURONIC ACID (HA) CONJUGATED TGFβ1 SIRNA
Authors: S.K. Yoon, S.W. Hong, P.S. Sung, C.-H. Park, M.J. Song, J.M. Yang, S.W. Choi, C.D. Lee, Y.S. Lee, S.K. Hahn
Journal: Journal of Hepatology (2011)
Can a pre-exercise test score predict prognosis in women with a low prevalence of coronary disease? The National heart, lung, and blood institute- sponsored women's ischemia syndrome evaluation (WISE) study
Authors: Anthony Morise, Marian B. Olson, C.Noel Bairey Merz, Sunil Mankad, William J. Rogers, Carl J. Pepine, Steven E. Reis, Barry L. Sharaf, George Sopko, Gerald M. Pohost, Leslee J. Shaw
Journal: Journal of the American College of Cardiology (2003)
Prevalence of Detectable C-Peptide According to Age at Diagnosis and Duration of Type 1 Diabetes
Authors: Asa K. Davis, Stephanie N. DuBose, Michael J. Haller, Kellee M. Miller, Linda A. DiMeglio, Kathleen E. Bethin, Robin S. Goland, Ellen M. Greenberg, David R. Liljenquist, Andrew J. Ahmann, Santica M. Marcovina, Anne L. Peters, Roy W. Beck, Carla J. Greenbaum
Journal: Diabetes Care (2014)

OBJECTIVE It is generally accepted that complete β-cell destruction eventually occurs in individuals with type 1 diabetes, which has implications for treatment approaches and insurance coverage. The frequency of residual insulin secretion in a large cohort of individuals at varying ages of diagnosis and type 1 diabetes duration is unknown. RESEARCH DESIGN AND METHODS The frequency of residual insulin secretion was determined by measurement of nonfasting serum C-peptide concentration in 919 individuals with type 1 diabetes according to prespecified groups based on age at diagnosis and duration of disease (from 3 to 81 years' duration). Stimulated C-peptide was measured in those with detectable nonfasting values and a group of those with undetectable values as control. RESULTS The overall frequency of detectable nonfasting C-peptide was 29%, decreasing with time from diagnosis regardless of age at diagnosis. In all duration groups, the frequency of C-peptide was higher with diagnosis age &amp;gt;18 years compared with ≤18 years. Nineteen percent of those with undetectable nonfasting C-peptide were C-peptide positive upon stimulation testing. CONCLUSIONS The American Diabetes Association’s definition of type 1 diabetes as “usually leading to absolute insulin deficiency” results in clinicians often considering the presence of residual insulin secretion as unexpected in this population. However, our data suggest that residual secretion is present in almost one out of three individuals 3 or more years from type 1 diabetes diagnosis. The frequency of residual C-peptide decreases with time from diagnosis regardless of age at diagnosis, yet at all durations of disease, diagnosis during adulthood is associated with greater frequency and higher values of C-peptide.
Abstract 4540: Follicle-stimulating hormone (FSH) enhances the proliferation of epithelial ovarian cancer cells by activating transient receptor potential channel C3 (TRPC3)
Authors: Xiang Tao, Hongyan Jin, Robert C. Bast, Yingtao Liu, Yinhua Yu, Youji Feng
Journal: Cancer Research (2011)

Abstract At present, epithelial ovarian cancer is the leading killer among all gynecological malignancies. Despite much research, development of this neoplasm is still not fully understood. The five-year survival rate for this disease still remains about 30%. Recent studies suggest that follicle-stimulating hormone (FSH) may play a major role in ovarian epithelial carcinogenesis. Our group has demonstrated that FSH stimulates the proliferation and invasion of ovarian cancer cells, inhibits apoptosis, and facilitates neovascularization by increasing vascular endothelial growth factor (VEGF) expression. To understand the mechanisms by which FSH stimulates ovarian cancer growth, we have performed gene expression arrays and confirmed changes in protein expression by Western blots. Interestingly, we found that FSH stimulation enhances expression of transient receptor potential channel C3 (TRPC3) at both mRNA and protein levels. Silencing TRPC3 expression by siRNA inhibited the ability of FSH to stimulate proliferation of ovarian cancer cell lines and to block apoptosis. TRPC channels are nonselective cation channels with permeability to Ca2+. Increases in cytosolic free Ca2+ can promote different physiological changes including cell growth, differentiation and death. TRPC3 is one of 7 TRPC family members. Our previous work has shown that TRPC3 contributes to the progression of human ovarian cancer. TRPC3 protein levels in human ovarian cancer specimens were greatly increased relative to those in normal ovarian specimens. Downregulating TRPC3 expression led to reduced proliferation, suppression of epidermal growth factor-induced Ca2+ influx, and decreased growth of xenografts. In this study, we further explored the interaction of FSH-TRPC3. FSH stimulation was associated with upregulation of TRPC3 levels and translocation of TRPC3 from the cytoplasm to cell membrane, facilitating the influx of Ca2+ after treatment with a TRPC3 specific agonist. Knocking down TRPC3 abrogated Akt/PKB phosphorylation by FSH stimulation, leading to decreased expression of down-stream effectors including survivin, HIF1α and VEGF. Our findings indicate that TRPC3 plays a significant role in the tumor-stimulating activity of FSH and could be a potential therapeutic target of ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4540. doi:10.1158/1538-7445.AM2011-4540
GM1 and Tumor Necrosis Factor-α, Overexpressed in Renal Cell Carcinoma, Synergize to Induce T-Cell Apoptosis
Authors: Tanya Das, Gaurisankar Sa, Cynthia Hilston, Daisuke Kudo, Patricia Rayman, Kaushik Biswas, Luis Molto, Ronald Bukowski, Brian Rini, James H. Finke, Charles Tannenbaum
Journal: Cancer Research (2008)

Abstract The ability to induce T-cell apoptosis is one mechanism by which tumors evade the immune system, although the molecules involved remain controversial. We found that renal cell carcinoma (RCC)–induced T-cell apoptosis was inhibited by &amp;gt;50% when cocultures were performed with ganglioside-depleted tumor cells, caspase-8–negative lymphocytes, or anti–tumor necrosis factor-α (TNFα) antibodies, suggesting that tumor gangliosides synergize with signals delivered through TNFα death receptors to mediate T-cell killing. The synergy between tumor-derived TNFα and the RCC-overexpressed ganglioside GM1 for killing resting T cells is corroborated by studies using purified GM1 and rTNFα, which indicate that a 48-hour pretreatment with the ganglioside optimally sensitizes the lymphocytes to a TNFα-induced apoptotic death. However, activated T cells, which synthesize TNFα themselves, can be killed by exogenous GM1 alone. RelA-overexpressing lymphocytes are protected from GM1 plus TNFα-mediated apoptosis, a finding consistent with our previous studies indicating that gangliosides inhibit nuclear factor-κB activation. These results are clinically relevant because, similar to T-cells cocultured with GM1-overexpressing RCC lines, T cells isolated from the peripheral blood of patients with metastatic RCC are also heavily coated with that tumor-shed ganglioside. This population of patient cells, unlike T cells isolated from normal donors, is highly susceptible to apoptosis induced by rTNFα or by metastatic patient sera, which contain elevated levels of the cytokine. This report thus extends our previous studies by demonstrating that tumor-derived TNFα enhances RCC apoptogenicity not only by inducing ganglioside synthesis but also by initiating receptor-dependent apoptosis in T cells in which the nuclear factor-κB activation pathway has been inhibited by GM1. [Cancer Res 2008;68(6):2014–23]
Clinical experience and results of a Sentinel Health Investigation related to indoor fungal exposure.
Authors: E Johanning, P Landsbergis, M Gareis, C S Yang, E Olmsted
Journal: Environmental Health Perspectives (1999)

This is a review of exposure conditions, clinical presentation, and morbidity of children and adults with indoor fungal exposure such as toxic Stachybotrys chartarum. Indoor exposure was characterized using different methods including microscopic, culture, cytotoxicity screening tests, and chemical analyses. Clinical case histories and physical and laboratory findings are presented of children (age < 18 years, n = 22; mean age 9 years; 60% females) and adults (age >18 years, n = 125; mean age 39 years, 67% females) who consulted an environmental health specialty clinic. In the pediatric patients' exposure history, widespread fungal contamination of water-damaged building materials with known toxic or allergic fungi was identified. Primarily disorders of the respiratory system, skin, mucous membranes, and central nervous system were reported. Some enumeration and functional laboratory abnormalities, mainly of the lymphatic blood cells, were observed, although no statistically significant differences were found. IgE or IgG fungi-specific antibodies, used as exposure markers, were positive in less than 25% of all tested cases. In an evaluation of a symptomatic girl 11 years of age (sentinel case investigation) living in an apartment with verified toxigenic fungi (i.e., S. chartarum), several health indicators showed improvement after exposure cessation.