tbuckley/cabot-search huggingface dataset:
Long-term Regulation of Genetically Modified Primary Hematopoietic Cells in Dogs
Authors: Kiyoshi Okazuka, Brian C Beard, David W Emery, Kerstin Schwarzwaelder, Michele R Spector, George E Sale, Christof von Kalle, Hans-Peter Kiem, C Anthony Blau
Journal: Molecular Therapy (2011)

We report long-term results from a large animal model of in vivo selection. Nine years ago, we transplanted two dogs (E900 and E958) with autologous marrow CD34+ cells that had been transduced with a gammaretrovirus vector encoding a conditionally activatable derivative of the thrombopoietin receptor. Receptor activation through administration of a chemical inducer of dimerization (CID) (AP20187 or AP1903) confers a growth advantage. We previously reported responses to two 30-day intravenous (i.v.) courses of AP20187 administered within the first 8 months post-transplantation. We now report responses to 5-day subcutaneous (s.c.) courses of AP20187 or AP1903 at months 14, 90, and 93 (E900), or month 18 (E958), after transplantation. Long-term monitoring showed no rise in transduced cells in the absence of drug. Retroviral insertion site analysis showed that 4 of 6 (E958) and 5 of 12 (E900) transduced hematopoietic cell clones persisted lifelong. Both dogs were euthanized for reasons unrelated to the gene therapy treatment at 8 years 11 months (E958) and 11 years 1 month (E900) of age. Three clones from E900 remained detectable in each of two secondary recipients, one of which was treated with, and responded to, AP1903. Our results demonstrate the feasibility of safely regulating genetically engineered hematopoietic cells over many years. We report long-term results from a large animal model of in vivo selection. Nine years ago, we transplanted two dogs (E900 and E958) with autologous marrow CD34+ cells that had been transduced with a gammaretrovirus vector encoding a conditionally activatable derivative of the thrombopoietin receptor. Receptor activation through administration of a chemical inducer of dimerization (CID) (AP20187 or AP1903) confers a growth advantage. We previously reported responses to two 30-day intravenous (i.v.) courses of AP20187 administered within the first 8 months post-transplantation. We now report responses to 5-day subcutaneous (s.c.) courses of AP20187 or AP1903 at months 14, 90, and 93 (E900), or month 18 (E958), after transplantation. Long-term monitoring showed no rise in transduced cells in the absence of drug. Retroviral insertion site analysis showed that 4 of 6 (E958) and 5 of 12 (E900) transduced hematopoietic cell clones persisted lifelong. Both dogs were euthanized for reasons unrelated to the gene therapy treatment at 8 years 11 months (E958) and 11 years 1 month (E900) of age. Three clones from E900 remained detectable in each of two secondary recipients, one of which was treated with, and responded to, AP1903. Our results demonstrate the feasibility of safely regulating genetically engineered hematopoietic cells over many years.
Hepatocyte growth factor induces collagenase (matrix metalloproteinase-1) via the transcription factor Ets-1 in human hepatic stellate cell line
Authors: Iwata Ozaki, Gang Zhao, Toshihiko Mizuta, Yoko Ogawa, Toshiya Hara, Susumu Kajihara, Akitaka Hisatomi, Takahiro Sakai, Kyosuke Yamamoto
Journal: Journal of Hepatology (2002)
Book Review Textbook of Ophthalmology Edited by Sunita Agarwal, with six others. 3026 pp., in four volumes plus index, illustrated. New Delhi, India, Jaypee Brothers Medical Publishers, 2002. (Distributed by Lippincott Williams &amp; Wilkins, Philadelphia.) $350. 81-7179-884-5
Authors: Duncan P. Anderson
Journal: New England Journal of Medicine (2003)
Stages of renal ontogenesis identified by monoclonal antibodies reactive with lymphohemopoietic differentiation antigens.
Authors: J L Platt, T W LeBien, A F Michael
Journal: The Journal of Experimental Medicine (1983)

Differentiation antigens of T and B lymphocytes were sought in human fetal and adult kidney tissues with monoclonal antibodies by indirect immunofluorescence. Antibodies that identify B cells (BA-1 and anti-B1) and leukemia-associated antigens (BA-2, BA-3, and J5) reacted with renal glomerular and tubular epithelium at characteristic stages of nephron development. BA-1 and BA-2 identified primitive epithelium of the glomerulus, and ureteral bud and nephron development was characterized by loss of BA-1 and BA-2 binding by visceral glomerular and proximal tubular epithelium. In contrast, J5 and BA-3 did not react with primitive epithelium but identified visceral and proximal tubular epithelium after appearance of the glomerular basement membrane and throughout subsequent nephron differentiation. Anti-B1 reacted with ureteral bud and distal nephron epithelium in more mature fetal tissues. Monoclonal antibodies that identify populations of T cells and thymocytes did not react with parenchymal cells of fetal or adult kidneys. They did identify interstitial mononuclear cells whose size and relative numbers appeared gestationally related. Monoclonal antibodies that recognize a human monomorphic HLA-DR determinant reacted with glomerular and peritubular capillaries as early as 11 wk of gestation. The distribution and density of HLA-DR expression appeared more related to gestation than nephron development. The relationship between renal parenchymal expression of lymphohemopoietic antigens and glomerular acquisition of C3b receptor activity was determined using C3b-coated fluoresceinated Escherichia coli. In fetal tissues, C3b receptor activity appeared developmentally related to the loss of determinants recognized by BA-1 and BA-2 and to the appearance of J5 and BA-3 reactivity with visceral glomerular epithelium. Tissue binding and comparative avidity of J5 and BA-3 antibodies was studied in a series of experiments, the results of which suggest that these antibodies are directed against the same epitope or closely related epitopes of the common acute lymphoblastic leukemia antigen. The common expression of differentiation antigens and C3b receptors by cells of lymphohemopoietic lineage and renal epithelia suggests the possibility of heretofore unrecognized commonality of function or developmental experience.
Comparison of haemodynamic responses to dobutamine and salbutamol in cardiogenic shock after acute myocardial infarction.
Authors: M B Fowler, A D Timmis, J P Crick, R Vincent, D A Chamberlain
Journal: BMJ (1982)

Nine patients with critically reduced cardiac output after acute myocardial infarction underwent a single cross-over comparison of dobutamine and salbutamol to compare the haemodynamic effects of these drugs, which have, respectively, predominantly beta 1-adrenergic and beta 2-adrenergic agonist activity. The responses were used to select the more appropriate treatment for individual patients. Only relatively small responses were obtained: those with poorest baseline measurements tended to show the least effect. When the results from the series were averaged, dobutamine (250-750 microgram/min) caused a small but progressive increase in cardiac index (1.8 to 2.2 1/min/m2) throughout the dose range. Systemic blood pressure was not increased, and calculated systemic vascular resistance fell from 25 to 19 units. Heart rate rose from 107 to 118 beats/min and stroke index from 17 to 19 ml/beat/m2. Pulmonary artery end-diastolic pressure fell from 18 to 15 mm Hg. Salbutamol (10-40 microgram/min) produced a similar progressive increase in cardiac index, from 1.6 to 2.21/min/m2. Systemic blood pressure was not altered, and systemic vascular resistance fell from 25 to 20 units. Heart rate rose from 105 to 119 beats/min and stroke index from 16 to 19 ml/beat/m2. Pulmonary artery end-diastolic pressure did not fall. Dobutamine and salbutamol have closely similar haemodynamic effects when used in cardiogenic shock after acute myocardial infarction. Both drugs increase cardiac index but heart rate also rises, and the increase in stroke index is relatively small. Mean arterial pressure is altered little by either agent, but dobutamine (in contrast with dopamine) tends to reduce pulmonary artery end-diastolic pressure, which may be beneficial.
Randomised trial of three approaches for marketing smoking cessation programmes to Australian general practitioners.
Authors: J. Cockburn, D. Ruth, C. Silagy, M. Dobbin, Y. Reid, M. Scollo, L. Naccarella
Journal: BMJ (1992)

OBJECTIVE--To compare three approaches for marketing a quit smoking intervention kit to general practitioners. DESIGN--Randomised trial of (a) personal delivery and presentation by an educational facilitator with a follow up visit six weeks later; (b) delivery to the receptionist by a friendly volunteer courier with a follow up phone call six weeks later, or (c) postal delivery with a follow up letter six weeks later. SETTING--Melbourne, Australia. SUBJECTS--264 randomly selected general practitioners. DATA COLLECTION--A research assistant visited each doctor four months after delivery and measured use of components of the kit. A questionnaire measuring perceptions of aspects of the kit and its delivery was completed by doctors. Costs of each approach were calculated. RESULTS--Doctors receiving the educational facilitator approach were significantly more likely than those receiving the other two approaches to have seen the kit, to rate the method of delivery as engendering motivation to try the kit, to have used one of the "intensive intervention" components from the kit, to report that they found the kit less complicated, and to report greater knowledge of how to use the kit. There were no significant differences in use of "minimal intervention" components of the kit, ratings of overall acceptability of delivery, perceptions of cultural and structural barriers to using the kit, and ratings of the overall acceptability of the kit. The cost of the educational facilitator approach ($A142/doctor) was 24 times that of the mailed approach. The volunteer courier approach ($A14) was twice the cost of the mailed approach. CONCLUSION--Educational facilitators and volunteer couriers do not seem to be cost effective strategies for distributing smoking interventions.
Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection
Authors: Richard K. Sterling, Eduardo Lissen, Nathan Clumeck, Ricard Sola, Mendes Cassia Correa, Julio Montaner, Mark S. Sulkowski, Francesca J. Torriani, Doug T. Dieterich, David L. Thomas, Diethelm Messinger, Mark Nelson
Journal: Hepatology (2006)

Liver biopsy remains the gold standard in the assessment of severity of liver disease. Noninvasive tests have gained popularity to predict histology in view of the associated risks of biopsy. However, many models include tests not readily available, and there are limited data from patients with HIV/hepatitis C virus (HCV) coinfection. We aimed to develop a model using routine tests to predict liver fibrosis in patients with HIV/HCV coinfection. A retrospective analysis of liver histology was performed in 832 patients. Liver fibrosis was assessed via Ishak score; patients were categorized as 0–1, 2–3, or 4–6 and were randomly assigned to training (n = 555) or validation (n = 277) sets. Multivariate logistic regression analysis revealed that platelet count (PLT), age, AST, and INR were significantly associated with fibrosis. Additional analysis revealed PLT, age, AST, and ALT as an alternative model. Based on this, a simple index (FIB-4) was developed: age ([yr] × AST [U/L]) / ((PLT [109/L]) × (ALT [U/L])1/2). The AUROC of the index was 0.765 for differentiation between Ishak stage 0–3 and 4–6. At a cutoff of <1.45 in the validation set, the negative predictive value to exclude advanced fibrosis (stage 4–6) was 90% with a sensitivity of 70%. A cutoff of >3.25 had a positive predictive value of 65% and a specificity of 97%. Using these cutoffs, 87% of the 198 patients with FIB-4 values outside 1.45–3.25 would be correctly classified, and liver biopsy could be avoided in 71% of the validation group. In conclusion, noninvasive tests can accurately predict hepatic fibrosis and may reduce the need for liver biopsy in the majority of HIV/HCV-coinfected patients. (HEPATOLOGY 2006;43:1317–1325.)
Serum amyloid P component binds to cell nuclei in vitro and to in vivo deposits of extracellular chromatin in systemic lupus erythematosus.
Authors: S M Breathnach, H Kofler, N Sepp, J Ashworth, D Woodrow, M B Pepys, H Hintner
Journal: The Journal of Experimental Medicine (1989)

Serum amyloid P component (SAP) is the single plasma protein that, from the milieu of whole normal human serum, undergoes specific calcium-dependent binding to isolated DNA and chromatin in vitro. We now report for the first time that SAP in whole serum also undergoes calcium-dependent binding to nuclei of epidermal cells in sections of normal human skin and to nuclei of fixed Hep-2 cells, a human epithelial cell line. Furthermore, and most importantly, SAP was detected in association with unusual globular dermal deposits of nuclear material in skin biopsies from two patients with systemic lupus erythematosus. This is the first evidence for binding of SAP to extracellular chromatin in vivo and supports the idea that SAP may have an important physiological role in the disposal of this material.
Catnip and Related Psychedelic Compounds
Authors: Vincent dePaul Lynch
Journal: JAMA (1969)

To the Editor:—  The authors mention that catnip is a member of the mint family, Labiatae; thyme and marjoram also belong in this family, and these items are the principal substances used as fillers in cheap or low-grade marihuana. In the same way that lactose is used to cut heroin to increase the monetary return, these substances may be added to marihuana. Some individuals who have never seen or smelled marihuana could not detect any differences when confronted with containers of either of the substances commonly used as spices. In fact, in an experiment conducted by this writer, a group of law-enforcement agents became convinced that the substance they were looking at and handling was marihuana when it was in reality, thyme.  Other members of the mint family have been reputed to have hallucinatory properties. Several years ago, Gordon Wasson described a Central American member of this species which was
Burns because of epilepsy
Authors: K K Hampton, R C Peatfield, T Pullar, H J Bodansky, C Walton, M Feely
Journal: BMJ (1988)

Reponses a un questionnaire de 134 malades atteints d'epilepsie: etude de la frequence, de la gravite et des circonstances des brulures, notamment au cours des crises. Precautions possibles
Endogenously synthesized peptide with an endoplasmic reticulum signal sequence sensitizes antigen processing mutant cells to class I-restricted cell-mediated lysis.
Authors: K Anderson, P Cresswell, M Gammon, J Hermes, A Williamson, H Zweerink
Journal: The Journal of Experimental Medicine (1991)

The HLA-A2-positive human mutant cell line T2 is not lysed by influenza virus-specific HLA-A2-restricted cytotoxic lymphocytes after virus infection. However, lysis does occur when cells are incubated with the antigenic influenza matrix protein-derived peptide M57-68. To examine the nature of this defect, T2 cells were transfected with two different plasmids. One plasmid encoded the peptide M57-68, and the other encoded the same peptide preceded by an endoplasmic reticulum translocation signal sequence. Mutant T2 cells expressing the M57-68 peptide without the signal sequence were not susceptible to lysis by M57-68-specific HLA-A2-restricted cytotoxic T lymphocytes, whereas T2 cells expressing the M57-68 peptide plus signal sequence were lysed effectively. Lysis of parental T1 cells with either plasmid was equally effective. These results suggest that the T2 mutant cells are defective in the transport of antigenic peptides from the cytosol into the secretory pathway.
Ethnic Differences in Pulmonary Function in Healthy Nonsmoking Asian-Americans and European-Americans
Authors: BRIAN KOROTZER, SOLITA ONG, JAMES E. HANSEN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We investigated ethnic differences in spirometry and gas transfer (Dl CO) in a young, healthy population of nonsmoking physicians and medical students aged 22–33 yr, of European or Asian descent. Each answered questions detailing ethnic background, medical history, level of physical activity, and length of residence in the United States. Spirometry and single-breath Dl CO maneuvers were performed in accordance with ATS standards. Venous blood was measured for hemoglobin (Hb). The same equipment was used to test all subjects. Data were analyzed by multiple linear regression. Eighty subjects were studied, with 20 in each of the following groups: European male, European female, Asian male, and Asian female. Asian values for forced vital capacity, forced expiratory volume in 1 s (FEV1), and alveolar volume (Va′ ) were significantly lower than for Europeans, but Dl CO, Dl CO/Va′ , and Dl CO/Va′ /Hb did not differ significantly. These differences could not be attributed to age, length of residence in the United States, activity level, or variance in baseline characteristics and anthropometric measurements, and therefore represent a true physiologic difference. Ethnic differences between individuals of Asian and European backgrounds should be considered when interpreting pulmonary function tests, especially when predicted values are based on populations of European descent.
MOVABLE FRAME FOR PROTECTING DELIRIOUS PATIENTS
Authors: M. A. Reasoner
Journal: JAMA (1924)

In the spring of 1922, there was constructed at the medical supply depot, Coblenz, Germany, a movable frame with netting for the purpose of enclosing a bed. It was based on a description given by Dr. H. C. Michie of a similar device he had seen in a hospital in Vienna. It was in use at the Station Hospital in Coblenz until this place was given up, and then forwarded to the Walter Reed General Hospital. As will be seen from the illustration, it consisted of an iron frame large enough to fit around and over a hospital bed. It had plenty of head room, and was covered with a heavy netting. This device serves effectually to restrain a patient with purposeless delirium without the constant services of an attendant. With the closed frame in place, it is impossible for such a patient either to get out or to fall
Skin-Electrode Impedance and Its Effect on Recording Cardiac Potentials
Authors: MADISON S. SPACH, ROGER C. BARR, JAMES W. HAVSTAD, E. CROFT LONG
Journal: Circulation (1966)

Skin-electrode impedance was measured for four different types of conventional electrocardiographic electrodes applied under different conditions. All types of contacts were frequency dependent; a decrease in impedance was found with increasing frequency. Occasionally, impedance values at a frequency range of 6 to 100 cycles per second were in the tens of thousands of ohms with all electrode types. Tracings obtained under working conditions were evaluated to determine the influence of skin-electrode impedance on the recorded data. Single channel electrocardiographs accurately recorded cardiac potentials; however, simultaneously recorded multiple channel data had considerable distortion in half of the subjects. Frank vectorcardiograms demonstrated significant amplitude loss in half of the patients, with the most prominent distortion occurring in the T wave as compared to QRS. The inclusion of a buffer amplifier between the skin-electrode contacts and the resistor network produced distortionfree tracings. The inclusion of such devices is suggested to obviate any potential error produced by the highest skin-electrode impedance contact values obtained under working conditions.
Autoradiographic characterization of beta adrenergic receptors in coronary blood vessels and myocytes in normal and ischemic myocardium of the canine heart.
Authors: K H Muntz, E G Olson, G R Lariviere, S D'Souza, A Mukherjee, J T Willerson, L M Buja
Journal: Journal of Clinical Investigation (1984)

This light microscopic autoradiographic study was performed to test the hypotheses that (a) the density of beta adrenergic receptors (BAR) may differ in various components of the heart and (b) BAR in certain components of the heart may exhibit a selective response to pharmacologic and pathological stimuli. Blocks of canine left ventricle were frozen and tissue sections cut and incubated in (-)[3H]dihydroalprenolol (DHA) to label the BAR. For total and nonspecific binding, serial sections were incubated with and without 10(-5) M (+/-)propranolol. Scintillation spectrometry of sections demonstrated rapid binding, saturability, stereospecificity, a dissociation constant (KD) of 3.2 +/- 0.5 nM (SD) (n = 3), and a maximal binding of 31.3 +/- 3.1 fmol/mg of tissue protein. Isoproterenol was 12.5 times more effective than norepinephrine in displacing DHA. Sections incubated with 10(-5) - 10(-8) M metoprolol, a beta one selective antagonist, demonstrated a KD of 0.7 X 10(-6) M. For autoradiography, emulsion-coated coverslips were attached to the slides. After exposure, the slides were developed and stained, and grain density quantified. Specific BAR binding (n = 4 dogs) was 1,047 +/- 131 (SEM) grains/10(-2) mm2 for myocardial arterioles, 219 +/- 30 for myocardial arteries, 31 +/- 12 for the proximal left anterior descending coronary artery (LAD), and 231 +/- 34 for cardiac myocytes. Specific binding in the presence of 10(-5) M metoprolol was reduced approximately 75% for both arterioles and myocytes. However, at 10(-6) M metoprolol, the percent reduction in specific DHA binding was greater for myocytes (50%) than for arterioles (0%), and at 10(-7) M metoprolol, the percent reduction in specific DHA binding was 17% for myocytes with no reduction over arterioles. After 1 h of LAD occlusion, a selective increase (18%) in BAR density occurred over cardiac myocytes, but not over blood vessels in the ischemic myocardium. Thus, (a) specific BAR binding was five times greater in arterioles than in small arteries and myocardium and 34 times greater than in the proximal LAD; (b) BAR of myocytes were more sensitive than those of arterioles to displacement by the beta one selective antagonist, metoprolol; and (c) a selective increase in BAR occurs in cardiac myocytes but not in blood vessels after 1 h of ischemia in this experimental model.
Chronic Mucocutaneous Candidiasis: Immunologic and Antibiotic Therapy
Authors: CHARLES H. KIRKPATRICK
Journal: Annals of Internal Medicine (1974)

Ten patients with chronic mucocutaneous candidiasis were studied immunologically and treated with either intravenous amphotericin B, transfer factor, or both of the agents. Five patients (late-onset cases) developed candidiasis after they were 5 years old, had less severe immunologic deficits, and responded to treatment with amphotericin B. Four of these patients have had remissions of 12 to 38 months, and in two patients negative, delayed candida skin tests became positive, suggesting recovery of immunologic function. The other five patients (early-onset cases) developed candidiasis during infancy or early childhood and had severe impairments of cellular immunity, often with complete anergy. Transfer factor from donors with positive skin tests caused conversion of delayed responses in these patients but did not produce beneficial or detrimental clinical effects. Two early-onset, anergic patients then received amphotericin and chronic transfer factor therapy; both have been free of cutaneous candidiasis for more than 2 years.