tbuckley/cabot-search huggingface dataset:
663. Gene Modified Human Mesenchymal Stem Cells Expressing Osteoprotegerin Reverse Osteoclast Activation in a Xenogeneic Murine Model of Multiple Myeloma
Authors: Neil Rabin, Chara Kyriakou, Arnold Pizzey, Clive Buckle, Matthew Prideaux, Peter Croucher, Amit Nathwani, Kwee Yong
Journal: Molecular Therapy (2006)

Bone disease in multiple myeloma (MM) is due to an increase in osteoclast (OCL) numbers, which is associated with an increase in RANK Ligand and reduction in osteoprotegerin (OPG). Previous studies have shown that systemic administration of recombinant OPG reduces MM bone disease, but the short half life of OPG limits its usefulness. Gene modified mesenchymal stem cells (MSCs) offer a potential means of delivering stable expression of therapeutic proteins. Bone marrow derived human MSCs were transduced with a self- inactivating bicistronic lentiviral vector containing human OPG and GFP (MSC-OPG). Control vector was identical except the OPG was cloned in reverse orientation (MSC-GPO). Efficient transduction (MOI=2, 5 consecutive days) was demonstrated by high GFP expression (96 % MSC-OPG, 92 % MSC-GPO). Stable transgene expression of hOPG occurred for beyond 20 passages, as shown by in vitro ELISA (MSC-OPG 8.9 ng/mL, MSC-GPO 0.7 ng/mL after 72 hours from 5 × 104 cells plated). Immunophenotype and differentiation potential of MSCs were maintained following transduction. A xenogeneic model of MM was developed. 1 × 107 KMSBM cells injected tail vein into beta 2 m NOD/SCID mice leads to tumour infiltration in the bone marrow at 6 weeks. Osteoclasts (OCL) lining the endocortical surface of the lumbar vertebrae were increased in tumour bearing mice as measured by the % covering the endocortical surface (% osteoclast perimeter, % OcPm). Mean % OcPm in KMSBM and PBS groups was 8.6 (+/− 4.8 sd) vs. 1.1 (+/− 0.9 sd) respectively (p=<0.01, n=5 both groups). Our hypothesis is that MSCs expressing OPG are able to prevent the increase in OCL number seen in tumour bearing mice. 1 x10 6 MSC-OPG (n = 6) or MSC-GPO (n = 6) were injected by tail vein 2, 3 and 4 weeks after KMSBM injection. Another group of mice received PBS and no MSCs or tumour (n = 4). All mice were culled at 6 weeks. MSC-GPO treated mice showed an increase in % OcPm compared to the PBS group (MSC-GPO mean % OcPM 3.5 (+/− 1.2 sd), PBS mean 1.3 (+/− 0.3 sd), p=0.028). MSC-OPG treated group had a reduction in %OcPm compared to MSC-GPO (MSC- OPG mean 1.9 (+/− 0.9 sd), MSC-GPO mean 3.5 (+/− 1.2 sd), p<0.01). %OcPm in MSC-OPG treated mice was similar to the PBS group. Conclusion: MSCs gene modified with osteoprotegerin are able to reverse OCL activation in a xenogeneic model of MM. Gene modified MSCs may have future potential in treating MM induced bone disease.
251 GENOTYPIC AND PHENOTYPIC CHARACTERIZATION OF GENOTYPE 2/3 HCV VARIANTS IN PATIENTS TREATED WITH TELAPREVIR ALONE OR IN COMBINATION WITH PEGINTERFERON ALFA-2A/RIBAVIRIN IN STUDY C209
Authors: S. De Meyer, G.R. Foster, A. Ghys, M. Beumont, B. Van Baelen, T.-I. Lin, G. Picchio
Journal: Journal of Hepatology (2010)
TCT-206 Incidence and clinical impact of Side Branch Occlusion After Bioresorbable Vascular Scaffold Implantation for Chronic Total Occlusions: Insight from the CTO-ABSORB pilot study
Authors: Beatriz Vaquerizo, Antonio Barros, Sandra Pujadas, Ester Bajo, DARLENE ESTRADA-YÁNEZ, Faustino Miranda-Guardiola, Marcelo Jimenez, Juan Cinca, Antonio Serra
Journal: Journal of the American College of Cardiology (2014)
Association Between Familial Hypercholesterolemia and Prevalence of Type 2 Diabetes Mellitus
Authors: Joost Besseling, John J. P. Kastelein, Joep C. Defesche, Barbara A. Hutten, G. Kees Hovingh
Journal: JAMA (2015)

Familial hypercholesterolemia is characterized by impaired uptake of cholesterol in peripheral tissues, including the liver and the pancreas. In contrast, statins increase the cellular cholesterol uptake and are associated with increased risk for type 2 diabetes mellitus. We hypothesize that transmembrane cholesterol transport is linked to the development of type 2 diabetes.To assess the association between type 2 diabetes prevalence and familial hypercholesterolemia.Cross-sectional study in all individuals (n = 63,320) who underwent DNA testing for familial hypercholesterolemia in the national Dutch screening program between 1994 and 2014.Deleteriousness and nondeleteriousness of familial hypercholesterolemia mutations were based on literature or laboratory function testing. Low-density lipoprotein (LDL) receptor mutations were considered more severe than apolipoprotein B gene (APOB) mutations, and receptor-negative LDL receptor mutations were considered more severe than receptor-deficient mutations.Prevalence of type 2 diabetes.The prevalence of type 2 diabetes was 1.75% in familial hypercholesterolemia patients (n = 440/25,137) vs 2.93% in unaffected relatives (n = 1119/38,183) (P < .001; odds ratio [OR], 0.62 [95% CI, 0.55-0.69]). The adjusted prevalence of type 2 diabetes in familial hypercholesterolemia, determined using multivariable regression models, was 1.44% (difference, 1.49% [95% CI, 1.24%-1.71%]) (OR, 0.49 [95% CI, 0.41-0.58]; P < .001). The adjusted prevalence of type 2 diabetes by APOB vs LDL receptor gene was 1.91% vs 1.33% (OR, 0.65 [95% CI, 0.48-0.87] vs OR, 0.45 [95% CI, 0.38-0.54]), and the prevalence for receptor-deficient vs receptor-negative mutation carriers was 1.44% vs 1.12% (OR, 0.49 [95% CI, 0.40-0.60] vs OR, 0.38 [95% CI, 0.29-0.49]), respectively (P for trend <.001 in both comparisons).In a cross-sectional analysis in the Netherlands, the prevalence of type 2 diabetes among patients with familial hypercholesterolemia was significantly lower than among unaffected relatives, with variability by mutation type. If this finding is confirmed in longitudinal analysis, it would raise the possibility of a causal relationship between LDL receptor-mediated transmembrane cholesterol transport and type 2 diabetes.
Prevention of Preeclampsia — A Reality?
Authors: F. G. Cunningham, N. F. Gant
Journal: New England Journal of Medicine (1989)

Preeclampsia and eclampsia, uniquely obstetrical complications, remain common causes of maternal and fetal morbidity and mortality. Like many other enigmatic diseases, preeclampsia has attracted over the centuries a series of treatment schemes, many of which have proved far more dangerous than the disease itself (for example, trephination and renal decapsulation). It is axiomatic that any disease can be better treated or prevented if its pathogenesis is known. This is also true of pharmacotherapy; when a drug's mechanisms of action are known, there is the promise of more rational and usually better therapeutic application. In this and an earlier issue of . . .
Coronavirus NL63 Illnesses in Infancy are a Risk Factor for Asthma at Age Six
Authors: T.E. Pappas, K.T. Sullivan Dille, W. Lee, K.A. Grindle, K.A. Roberg, D.F. Da Silva, C.J. Tisler, E.L. Anderson, K.M. Hansen, R.A. Grabher, L.E. Pleiss Salazar, M.D. Evans, R. Gagnon, J.E. Gern, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2007)

RATIONALE: In infancy, rhinovirus illnesses and severe RSV bronchiolitis indicate increased risk for recurrent wheezing and asthma, but there is less information about other viruses. We evaluated the frequency and severity of metapneumovirus (HMPV) and coronavirus (HCV) infections in a high-risk group of infants. METHODS: Nasal lavage samples were obtained in the first year of life during scheduled study visits and symptomatic respiratory illnesses as part of the Childhood Origins of Asthma Project (COAST). Samples (n = 567) were analyzed by Respiratory Multicode Assay (RMA) for HMPV, HCV-229E, HCV-OC43, HCV-NL63 and HCV-SARS. RESULTS: HMPV was isolated in 10.7% of samples during illnesses (n = 291), and also occurred with other respiratory viruses (4.8%). 47.8% of HMPV illnesses included wheezing. HCV were isolated in 19.2% of the samples during illnesses and included HCV-OC43 (10.0%) and HCV-NL63 (9.6%). In addition, HCV was commonly detected together with other respiratory viruses (6.5%). Of all HCV illnesses (n = 42), 33.3% included wheezing; however, HCV-NL63 had a significantly higher wheezing rate compared to HCV-OC43 (37.5% vs. 4.5%, p = 0.028). Children who had at least one HCV-NL63 illness during infancy were significantly more likely to have asthma at age 6 compared to those without HCV-NL63 illnesses (52.2% vs. 25.0%, p = 0.007). Having either HCV-OC43 or HMPV was not a risk factor for asthma at age 6. CONCLUSIONS: Improvements in viral diagnostics has allowed for identification of viruses that are difficult to culture. In infancy, HCV-NL63, HCV-OC43 and HMPV were significant causes of wheezing illnesses, however, only HCV-NL63 was significantly associated with asthma development at age six.
Pseudonormal Diastolic Filling Unmasked With Glyceryl Trinitrate in Patients With Type 2 Diabetes With Poor Metabolic Control
Authors: Gillian A. Whalley, Warwick Bagg, Robert N. Doughty, Greg Gamble, Geoff Braatvedt, Norman Sharpe
Journal: Diabetes Care (2001)

Poirier et al. (1) report very interesting data regarding pseudonormal diastolic filling in men who are free of clinical heart disease and have well-controlled diabetes. Specifically, 28% of their subjects had a pseudonormal filling pattern, which was detected using a Valsalva maneuver and/or pulmonary venous Doppler (PVD). We conducted a similar study in 34 high-risk type 2 diabetic patients (16 men, 18 women) who were middle-aged (mean age 55.8 years), obese (BMI 30.6 kg/m2), and had poor metabolic control (HbA1c 10.6%, fasting blood glucose 13.4 mmol/l). None of the patients had a history of heart failure or myocardial infarction, and we included patients with controlled hypertension. The patients underwent echocardiography methods similar to those used by Poirier et al. (1), although preload reduction was achieved …
Listening to Prozac: A Psychiatrist Explores Antidepressant Drugs and the Remaking of Self
Authors: James J. Brophy
Journal: JAMA (1994)

Kramer vs Kramer. Kramer, the psychotherapist, vs Kramer, the psychopharmacologist. Kramer, the ethicist, vs Kramer, the pragmatist. Kramer, the eclectic psychiatrist, is in conflict and transition, representative of that which envelops the theory and practice of psychiatry. They are elucidated in this thoughtful and refreshingly provocative book, which bridges Freudian, behavioral, social, neuroanatomic, and pharmacologic approaches to an understanding of brain function. Kramer, the provocateur, challenges the diagnostic presumptions, psychoanalytic concepts, and cultural ramifications in patients with a wide variety of personality traits significantly altered by the serotonin reuptake inhibitor fluoxetine hydrochloride—Prozac. Kramer, the introspective clinician, covers such common problems as depression, compulsion, rejection sensitivity, stress, kindling, risk, self-esteem, inhibition, pleasure, and anhedonia. He traces the effects of Prozac on these conditions, noting the remarkable changes wrought, changes that were previously thought to occur only with extensive psychotherapy. The transformative powers of the medication on the sense of self clearly
Increased Sodium-Lithium Countertransport in College Students With Elevated Blood Pressure
Authors: Richard Cooper, Daniel LeGrady, Seraphim Nanas, Maurizio Trevisan, Mohammed Mansour, Phillip Histand, David Ostrow, Jeremiah Stamler
Journal: JAMA (1983)

Blood pressure screening was carried out on a university campus to identify early hypertension or high-normal BP in young adults. Compared with normotensive control subjects of a similar age, drawn from the same population, persons identified as being at the upper end of the BP distribution had significantly increased levels of sodium-lithium counter-transport. This difference persisted when other potential confounding variables, eg, overweight, sex, ethnicity, sodium excretion, and age, were taken into account. A positive family history was associated with slightly higher levels of sodium-lithium countertransport, although the effect could be explained by higher present levels of BP. These data suggest that abnormalities of cation transport are present early in the course of the development of hypertension. Measurement of transport levels may provide an estimate of risk of hypertension and allow identification of susceptible persons. (<i>JAMA</i>1983;249:1030-1034)
A single split-signal FISH probe set allows detection of TAL1translocations as well as SIL-TAL1 fusion genes in a single test
Authors: M van der Burg, B Smit, B Brinkhof, BH Barendregt, MCM Verschuren, M Dib, HB Beverloo, JJM van Dongen, AW Langerak
Journal: Leukemia (2002)
The Structure of Human High Density Lipoprotein and the Levels of Apolipoprotein A-I in Plasma as Determined by Radioimmunoassay
Authors: Gustav Schonfeld, Barbara Pfleger
Journal: Journal of Clinical Investigation (1974)

The major apoprotein of high density lipoprotein is apolipoprotein A-I (ApoA-I). In addition to being a structural component of this class of lipoproteins, ApoA-I also has a physiologic role as an activator of lecithin-cholesterol acyl transferase, an enzyme important in the metabolism of all lipoproteins.
Epstein-Barr virus-associated lymphoproliferative eruption with progression to large granular lymphocytic leukaemia
Authors: K-H. CHO, C-W. KIM, O-S. KWON, S-G. YANG, K-C. PARK, M-H. PARK, H-I. CHO, J-G. KIM
Journal: British Journal of Dermatology (1997)

A 12-year-old Korean girl gave a 9-year history of recurrent necrotizing papules and vesicles on the face, scalp and extremities. Skin biopsy specimens showed an atypical lymphoreticular infiltrate with vasculitis in the dermis and subcutis. In situ hybridization demonstrated latent infection by Epstein-Barr virus (EBV) of the lymphoid cells in the dermis. The disease was diagnosed as an EBV-associated lymphoproliferative skin eruption presenting as recurrent necrotic papulovesicles. The patient subsequently developed large granular lymphocytic leukaemia of natural killer cell origin. Our observations suggest that a patient with an EBV-associated lymphoproliferative skin eruption presenting with recurrent necrotic papulovesicles might progress to develop leukaemia as well as lymphoma.
Project Hope Abroad
Authors: Paul H. Altrocchi
Journal: JAMA (1972)

At a time when our own healthcare delivery system is undergoing nationwide scrutiny and is receiving critical attack from several directions, it is an enlightening and educational experience to work with an organization which, since its inception, has been totally devoted to the analysis and upgrading of health education and delivery throughout the world. The major purpose of Project Hope is medical teaching. Considering the magnitude of the medical and population problems in the countries visited by Project Hope, merely functioning as a medical-service ship could not possibly have a significant effect upon the health-welfare of any country. The purpose, therefore, has been to teach and train physicians, dentists, nurses, technicians, pharmacists, dieticians, public health workers, and all other levels of paramedical personnel in their own medical environment so that they, in turn, can train others. The educational impact thus long overlasts the tenmonth stay of the ship in a
Tuberculosis and Migrant Farm Workers
Authors: Dixie E. Snider
Journal: JAMA (1991)

No reliable figure is available for the number of migrant farm workers and their family members in the United States, but estimates developed by the Migrant Health Program1indicate that there may be between 3 and 5 million migrant and seasonal farm workers. And no system is in place to measure the magnitude of the tuberculosis (TB) problem in this highly mobile population, but in a 1984 to 1985 Centers for Disease Control survey of TB cases reported in 29 states, farm laborers accounted for more than 5% of all employed cases (Centers for Disease Control, unpublished data, December 1987).  In this issue ofJAMA, Ciesielski et al2report a population-based study of TB in a random sample of migrant farm workers conducted in 1988 in North Carolina. There were several significant findings from this study, but the most striking was the discovery of active TB in 0.47%
CHARACTERISTICS OF GROWTH OF SARCOMA AND CARCINOMA CULTIVATED IN VITRO
Authors: Robert A. Lambert, Frederic M. Hanes
Journal: The Journal of Experimental Medicine (1911)

1. The transplantable sarcomata of rats and mice grow very readily by the method of cultivating tissues in vitro. 2. Sarcomatous tissue grows in conformity to a type which may be regarded as characteristic for tissues of mesenchymal origin. 3. The growth of sarcoma cells in vitro consists in ameboid wandering into the surrounding plasma, karyokinetic proliferation. and evidences of active metabolism on the part of the cells. 4. Mouse carcinomata can be cultivated in vitro. The outgrowth of carcinoma cells assumes a sheet-like form, only one cell in thickness. They migrate into the plasma by ameboid movement, the advancing edge showing numerous prolongations of the cytoplasm into pseudopods. 5. Karyokinetic figures are frequently seen in growing carcinoma cells. The cells show evidences of active metabolism. 6. Both sarcoma and carcinoma cells cultivated in vitro show active phagocytosis; carmin particles placed in the plasma are taken up rapidly by the growing cells.
Sex Differences of Age-Dependent Changes of Insulin Sensitivity in Japanese Nondiabetic Subjects
Authors: Michio Otsuki, Soji Kasayama, Hiroshi Saito, Mikio Mukai, Masafumi Koga
Journal: Diabetes Care (2005)

lial cell line-derived neurotrophic factor (GDNF) belongs to the neurotrophic factor family.GDNF functions are not restricted to neurons but are also implicated in glial cell development (1).We observed high expression levels of GDNF receptor family ␣-component 2 (GFR␣2) in epiretinal membranes (ERMs) in proliferative diabetic retinopathy (PDR), indicating the involvement of GFR␣2 in ERM formation in PDR (2).Here, we examined the vitreous of patients with PDR for the presence of GDNF.We assayed GDNF levels in vitreous and serum samples from 75 consecutive patients with PDR (54 patients) and macular hole (nondiabetic control subjects, 21 patients) who underwent vitrectomy.PDR was classified as active (33 patients) when there were perfused, multibranching iridic or preretinal capillaries and as quiescent (21 patients) when only large vessel or fibrosis was present.Informed consent was obtained from each patient.Undiluted vitreous samples were obtained during the vitrectomy before intraocular infusion.Enzyme-linked immunosorbent assay was performed to determine GDNF level using a commercially available immunoassay kit (Promega, Madison, WI).Mann-Whitney U test was used to compare GDNF levels.GDNF was undetectable in all the serum samples examined.Intravitreous GDNF level was significantly higher in the PDR patients (means Ϯ SD: 156.1 Ϯ 221.0 pg/ml) than in the control subjects (26.5 Ϯ 53.2 pg/ml) (P ϭ 0.0042).Intravitreous GDNF level was significantly higher in active PDR (206.0Ϯ 250.7 pg/ ml) than in quiescent PDR (77.7 Ϯ 135.5 pg/ml) (P ϭ 0.0388).Glial cells are one of the main components of ERMs.Our previous study (2) showed that GFR␣2 mRNA expression level is significantly higher in PDR ERMs than in idiopathic ERMs, and this high expression level is specific for GFR␣2 among neurotrophin receptors.GFR␣2 protein is detected in the glial component of PDR ERMs.These results suggest that GDNF is involved in the formation of the glial cell component of PDR ERMs.Results of the present study support this suggestion.Because GDNF increases basic fibroblast growth factor (bFGF) production in Mu ¨ller cells (3), released bFGF may stimulate endothelial proliferation.In this study, GDNF was undetectable in the serum samples.It is suggested that the increased level of vitreous GDNF in PDR reflects intraocular GDNF production but not breakdown of the bloodretina barrier.In conclusion, intravitreous GDNF level increased in PDR and was associated with the activity of PDR.These results suggest that GDNF is involved in the pathogenesis of PDR.
Endoscopic Neodymium-YAG Laser Palliation of Nonresectable Esophageal Malignancy
Authors: JOHN P. CELLO
Journal: Annals of Internal Medicine (1985)

Seven men and five women with nonresectable esophageal carcinoma were treated endoscopically with the neodymium-YAG (yttrium-aluminum-garnet) infrared laser. Before laser fulguration, tumors were dilated directly with metal olive dilators. Before treatment, mean tumor length was 5 cm with luminal occlusion averaging more than 80%. After a mean of 3.3 treatment sessions spanning 18.5 days, all patients had substantial immediate palliation. Continued symptomatic relief was noted during follow-up (mean, 83 days; range, 8 to 206 days).
915 INFLUENCE OF PNPLA3 SNP ON HEPATIC STEATOSIS AND FIBROSIS PROGRESSION IN HIV-HCV COINFECTED PATIENTS
Authors: B.A. Payer, T. Reiberger, J. Stift, M.C. Aichelburg, F. Breitenecker, A. Rieger, M. Peck-Radosavljevic
Journal: Journal of Hepatology (2012)
A CASE OF SYSTEMIC BLASTOMYCOSIS
Authors: ROBERT T. MORRIS
Journal: JAMA (1913)

<h3>History.</h3> —Dr. B. H. A., aged 37, Brownwood, Tex., was admitted to the Post-Graduate Hospital, Feb. 28, 1913. Family history and personal history have no important bearing in the report, but points in past history may be mentioned. The patient suffered from "malaria" for several months when a young child, but did not remember any other illness. At the age of 18 he suffered from what was probably acute appendicitis, but was not operated on. For the past eight or ten years the patient has usually had a severe cold every Winter, coughing for about a fortnight and then recovering. During the winter of 1911-1912 he coughed nearly all winter. The sputum was mucopurulent and scanty never bloody or with odor. <h3>Present Illness.</h3> —This dated from November, 1912. The patient went from Texas to Chicago and engaged in post-graduate medical work, including necropsies and dissections. Soon after arrival in Chicago,
Treatment of Status Epilepticus-Reply
Authors: Gastone G. Celesia
Journal: JAMA (1977)

<h3>In Reply.—</h3> Dr Wilkinson's comments raise an important factor in the treatment of status epilepticus: the potential danger of therapy due to the narrow margin of safety between therapeutic and lethal doses of anticonvulsants. All the drugs used to treat status epilepticus can be lethal if they are given in overdosage or too rapidly. Careful monitoring of respiration and cardiac function must be carried out during the administration of anticonvulsants. Any drug administered intravenously should be given slowly. The possibility of cardiac or respiratory arrest must be considered in every case and appropriate precautions taken. The physician must be prepared to resuscitate the patient. Drugs are not the only cause of cardiac system depression; the convulsive status per se often causes death by sudden cardiovascular collapse.<sup>1</sup> Dr Wilkinson's anecdotal description of his experience may lead to misinterpretation. Amobarbital sodium, as well as secobarbital sodium and hexobarbital, have been used