tbuckley/cabot-search huggingface dataset:
Adenovirus-Based Phospholamban Antisense Expression as a Novel Approach to Improve Cardiac Contractile Dysfunction
Authors: Karin Eizema, Henry Fechner, Karel Bezstarosti, Sonja Schneider-Rasp, Arnoud van der Laarse, Haili Wang, Heinz-Peter Schultheiss, Wolfgang C. Poller, Jos M. J. Lamers
Journal: Circulation (2000)

Background —A decrease in sarcoplasmic reticulum Ca 2+ pump (SERCA2) activity is believed to play a role in the impairment of diastolic function of the failing heart. Because the expression ratio of phospholamban (PL) to SERCA2 may be a target to improve contractile dysfunction, a PL antisense RNA strategy was developed under the control of either a constitutive cytomegalovirus (CMV) or an inducible atrial natriuretic factor (ANF) promoter. The latter is upregulated in hypertrophied and failing heart, allowing “induction-by-disease” gene therapy. Methods and Results —Part of the PL cDNA was cloned in antisense and sense directions into adenovectors under the control of either a CMV (Ad5CMVPLas and Ad5CMVPLs, respectively) or ANF (Ad5ANFPLas and Ad5ANFPLs, respectively) promoter. Infection of cultured rat neonatal cardiomyocytes with Ad5CMVPLas reduced PL mRNA to 30±7% of baseline and PL protein to 24±3% within 48 and 72 hours, respectively. The effects were vector dose dependent. Ad5CMVPLas increased the Ca 2+ sensitivity of SERCA2 and reduced the time to 50% recovery of the Ca 2+ transient. A decrease of PL protein was also achieved by infection with Ad5ANFPLas, and the presence of the hypertrophic stimulus, endothelin-1, led to enhanced downregulation of PL. The adenovectors expressing PL sense RNA had no effect on any of the tested parameters. Conclusions —Vector-mediated PL antisense RNA expression may become a feasible approach to modulate myocyte Ca 2+ homeostasis in the failing heart. The inducible ANF promoter for the first time offers the perspective for induction-by-disease gene therapy, ie, selective expression of therapeutic genes in hypertrophied and failing cardiomyocytes.
Targeting Human B-cell Malignancies through Ig Light Chain–Specific Cytotoxic T Lymphocytes
Authors: Jinsheng Weng, Soung-Chul Cha, Satoko Matsueda, Gheath Alatrash, Michael S. Popescu, Qing Yi, Jeffrey J. Molldrem, Michael Wang, Sattva S. Neelapu, Larry W. Kwak
Journal: Clinical Cancer Research (2011)

The variable regions of Ig (idiotype, Id) expressed by malignant B cells can be used as tumor-specific antigens that induce humoral and cellular immunity. However, epitopes derived from Id that stimulate human CD8(+) T-cell immunity are incompletely characterized.The clonal Ig V(L) of human myeloma cell line U266 and five primary B-cell tumors were sequenced, and peptides corresponding to the Ig V(L) region were tested for their ability to stimulate CTLs from 10 HLA-A*0201-positive normal donors. The CTLs thus generated were tested against peptide-pulsed T2 cells and autologous tumor cells.Fourteen peptides derived from Ig light chain (V(L)) of U266 and primary B-cell tumors were used to generate 68 CTLs lines that specifically produced IFN-γ when cocultured with peptide-pulsed T2 cells. These CTLs lysed peptide-pulsed T2 cell as well as U266 or autologous tumor targets in an HLA class I-dependent manner. Sequence analysis revealed shared V(L) T-cell epitopes in U266 and primary B-cell tumors, not previously reported within Ig heavy chain (V(H)) sequences.This study thus identifies novel immunogenic CTLs epitopes from Id V(L), suggests that they are naturally presented on the surface of B-cell malignancies, and supports their inclusion in next-generation Id vaccines. The ability to prime T cells derived from normal HLA-matched donors, rather than patients, may also have direct application to current strategies, designed to generate allogeneic tumor-specific T cells for adoptive transfer.
Autoimmune thrombocytopenic purpura and <i>Helicobacter pylori</i> infection effectivity during childhood
Authors: Sevgi Yetgin, Hülya Demir, Deniz Arslan, Selma Ünal, Nurten Koçak
Journal: American Journal of Hematology (2005)

To the Editor: The association of hematologic malignancies in Klinefelter syndrome, in which the chromosomal abnormality of XXY is observed, has rarely been reported in acute myeloblastic leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, myelodysplastic syndrome, or malignant lymphoma [1].It is not yet known how this chromosomal abnormality affects hematopoiesis.We encountered a case of severe thrombocytopenia associated with idiopathic thrombocytopenic purpura and cerebral hemorrhage, which responded to cyclosporine administration.A 27-year-old male complained of severe headache and was admitted to the neurosurgery department for cerebral hemorrhage.CBC demonstrated RBC 434Â10 4 /ml, Hb 13.4 g/dL, Hct 38%, platelets 1.1Â10 4 /mL, and WBC 18,600/ mL with normal differentials.Bone marrow aspiration smear demonstrated normocellular marrow, M/E 2.93, megakaryocytes were sufficiently present, and there were no leukemic or dysplastic cells of any hematopoietic lineage.Platelet-associated antigen was 1,232 ng/10 7 cells (normal value, 9-25 ng/10 7 ).The patient was diagnosed with idiopathic thrombocytopenic purpura.He underwent surgery to evacuate hematoma after the platelet count was increased by platelet transfusion and high-dose immunoglobulin administration.Postoperatively, he was referred to hematology and initially treated with corticosteroid administration starting at 60 mg/day and then tapered over 3 months.However, the platelet count did not increase at all.Subsequently, cyclosporine (200 mg/day) was administered, and the platelet count increased after a month to 10Â10 4 /ml.During this treatment, chromosomal analysis of bone marrow cells was demonstrated to be 47, XXY, and that of the peripheral blood showed the same phenotype.This patient was diagnosed with idiopathic thrombocytopenia purpura, because only thrombocytopenia was observed and there were no dysplastic cells or additional chromosome abnormalities.There are no reports of thrombocytopenia due to idiopathic thrombocytopenic purpura associated with Klinefelter syndrome.Thrombocytopenia in our patient may have been pre-senting an isolated thrombocytopenia due to refractory cytopenia of myelodysplastic syndrome [2], because immune pathogenesis and preleukemic state are considered in myelodysplastic syndrome, and our patient responded to cyclosporine administration.Careful follow-up of this patient is necessary.
Activation of angiotensin II type 1 receptor-associated protein exerts an inhibitory effect on vascular hypertrophy and oxidative stress in angiotensin II-mediated hypertension
Authors: Hiromichi Wakui, Toru Dejima, Kouichi Tamura, Kazushi Uneda, Koichi Azuma, Akinobu Maeda, Masato Ohsawa, Tomohiko Kanaoka, Kengo Azushima, Ryu Kobayashi, Miyuki Matsuda, Akio Yamashita, Satoshi Umemura
Journal: Cardiovascular Research (2013)

Activation of tissue angiotensin II (Ang II) type 1 receptor (AT1R) plays an important role in the development of vascular remodelling. We have shown that the AT1R-associated protein (ATRAP/Agtrap), a specific binding protein of AT1R, functions as an endogenous inhibitor to prevent pathological activation of the tissue renin-angiotensin system. In this study, we investigated the effects of ATRAP on Ang II-induced vascular remodelling.Transgenic (Tg) mice with a pattern of aortic vascular-dominant overexpression of ATRAP were obtained, and Ang II or vehicle was continuously infused into Tg and wild-type (Wt) mice via an osmotic minipump for 14 days. Although blood pressure of Ang II-infused Tg mice was comparable with that of Ang II-infused Wt mice, the Ang II-mediated development of aortic vascular hypertrophy was partially inhibited in Tg mice compared with Wt mice. In addition, Ang II-mediated up-regulation of vascular Nox4 and p22(phox), NADPH oxidase components, and 4-HNE, a marker of reactive oxygen species (ROS) generation, was significantly suppressed in Tg mice, with a concomitant inhibition of activation of aortic vascular p38MAPK and JNK by Ang II. This protection afforded by vascular ATRAP against Ang II-induced activation of NADPH oxidase is supported by in vitro experimental data using adenoviral transfer of recombinant ATRAP.These results indicate that activation of aortic vascular ATRAP partially inhibits the Nox4/p22(phox)-ROS-p38MAPK/JNK pathway and pathological aortic hypertrophy provoked by Ang II-mediated hypertension, thereby suggesting ATRAP as a novel receptor-binding modulator of vascular pathophysiology.
Some Psychologic Vulnerabilities of Physicians
Authors: George E. Vaillant, Nancy Corbin Sobowale, Charles McArthur
Journal: New England Journal of Medicine (1972)

The childhoods of 47 physicians were compared with those of 79 socioeconomically matched controls in occupations other than medicine. During 30 years of adult life, drug use, marital instability and resort to psychotherapy of the physicians was also compared with that of the controls. Physicians, especially those involved in direct patient care, were more likely than controls to have relatively poor marriages, to use drugs and alcohol heavily, and to obtain psychotherapy. Although these difficulties are often assumed to be occupational hazards of medicine, their presence or absence appeared to be strongly associated with life adjustment before medical school. Only the physicians with the least stable childhoods and adolescent adjustments appeared vulnerable to these occupational hazards. The findings may contribute to the medical and psychologic management of physician patients.
Ambulatory Blood Pressure Recording
Authors: Hans R. Brunner, Bernard Waeber
Journal: Annals of Internal Medicine (1992)

Problems with therapeutic conclusions based on intervention trials, Andrew J.S. Coats and Peter Sleight from invasive to non-invasive ambulatory blood pressure recording, Edward Bernard Raferty ambulatory blood pressure and assessment of cardiovascular risk, Dorothee Perloff and Maurice Sokolow how to deal with blood pressure variability, G. Parati et al borderline hypertension, Michael A. Weber et al home monitoring of blood pressure - an alternative to ambulatory monitoring, Thomas G. Pickering efficacy assessment of antihypertensive therapy, Bernard Waeber et al a pragmatic look at ambulatory blood pressure monitoring, Hans R. Brunner et al.
The War on Drugs: Time to Relocate the Battlefield?-Reply
Authors: Marsha F. Goldsmith
Journal: JAMA (1995)

ABSTRACT In Reply. —The JAMA Medical News series of articles about illegal drug use in the United States was meant as a chronicle, not a campaign. These articles sought to transcend the us vs them point of view and open to more extended discussion a medical and legal controversy demanding thoughtful consideration. From the reader response received to date, they appear to have begun to do so.
Arrest of epidermal growth factor-dependent growth in fetal hepatocytes after ethanol exposure.
Authors: G I Henderson, G S Baskin, J Horbach, P Porter, S Schenker
Journal: Journal of Clinical Investigation (1989)

Exposure of the fetal rat hepatocyte to ethanol in vitro blocks epidermal growth factor (EGF)-dependent cell replication. To define possible mechanisms for this growth arrest, we determined the effects of ethanol on EGF binding and EGF receptor (EGF-R) levels. During a 24-h exposure to ethanol (1.7 mg/ml, 31 mM), cell replication was completely blocked while EGF binding per cell doubled. This effect was no specific for EGF, with variable degrees of increased binding noted for insulin, transferrin, and glucagon. Significantly increased EGF binding was seen after 6 h of ethanol exposure, and both growth arrest and enhanced EGF binding were reversed within 12 h of ethanol withdrawal. Increases in both "high" and "low" affinity sites were seen, with no changes in the apparent Kd's. Total RNA, beta-actin mRNA, and EGF-R mRNA were increased 50-70% in ethanol exposed cells. However, direct measurements of EGF-R synthesis rates by [35S]methionine incorporation revealed no differences between control and ethanol exposed cells. Internalization of EGF-R was significantly altered by ethanol exposure. A 2-h incubation resulted in the internalization of 57% of the ligand in control cells, while only 31% of bound EGF was internalized in the ethanol exposed cells. Thus, the enhanced EGF binding may be due to decreased efficiency of internalization.
Hypernatraemia in Netherton's syndrome
Authors: B.-Z. Garty
Journal: British Journal of Dermatology (1987)

Journal Article Hypernatraemia in Netherton's syndrome Get access B.‐Z. Garty B.‐Z. Garty Division of Allergy‐Immunology‐Pulmonology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue 5, 1 November 1987, Page 672, https://doi.org/10.1111/j.1365-2133.1987.tb07511.x Published: 01 November 1987
Sleeping Beauty Vector System Moves Toward Human Trials in the United States
Authors: David A Williams
Journal: Molecular Therapy (2008)

In a public review of a proposed clinical gene transfer trial, the National Institutes of Health Recombinant DNA Advisory Committee (NIH RAC) heard details in June 2008 of what is the first human trial in the United States utilizing the Sleeping Beauty (SB) transposon system. The trial is being proposed by Partow Kebriaei and Laurence Cooper at the University of Texas MD Anderson Cancer Center and collaborator Perry Hackett at the University of Minnesota. This trial will transfer genetically altered T cells into patients with CD19+ B-lymphoid malignancies.
Hodgkin's Disease — Prognosis, Treatment and Etiologic and Immunologic Considerations
Authors: Alan C. Aisenberg
Journal: New England Journal of Medicine (1964)

TWO decades have passed since the publication of the classic Medical Progress series on Hodgkin's disease by Jackson and Parker.1 In an overall assessment the disease remains, as it was in 1944, a fascinating but frustrating pathological and clinical entity of unknown etiology and usually fatal outcome. Nevertheless, despite such a negative summation, much has been learned in the last twenty years. Investigations of Hodgkin's disease itself and in the tumor-virus field in general place the ignorance of etiology in new perspective. A number of careful studies of prognosis allow the notoriously uncertain course of the disease to be predicted . . .
In vivo modulation of glucocorticoid receptor mRNA by inhaled fluticasone propionate in bronchial mucosa and blood lymphocytes in subjects with mild asthma
Authors: Olof Andersson, Tobias N. Cassel, Reidar Grönneberg, Mikael Brönnegård, Pontus Stierna, Magnus Nord
Journal: Journal of Allergy and Clinical Immunology (1999)
Baroreflex control of plasma norepinephrine and heart period in healthy subjects and diabetic patients.
Authors: D L Eckberg, S W Harkins, J M Fritsch, G E Musgrave, D F Gardner
Journal: Journal of Clinical Investigation (1986)

Resting diabetic patients may have excessively rapid heart rates, reduced heart rate variability, and subnormal plasma catecholamine levels. Although all of these abnormalities may relate in some way to baroreceptor reflex function, there have been surprisingly few attempts to evaluate systematically baroreflex mechanisms in diabetic patients. Accordingly, we studied autonomic responses over a range of pharmacologically induced arterial pressure changes in 10 unselected young adult insulin-dependent diabetic patients who had no symptoms of autonomic neuropathy, and 12 age-matched nondiabetic subjects. Sympathetic responses were estimated from antecubital vein plasma norepinephrine levels, and parasympathetic responses were estimated from electrocardiographic R-R intervals and their variability (standard deviation). Both were correlated with other noninvasive indexes of peripheral and central nervous system function. Multiple derangements of baroreflex function were found in the diabetic patients studied. Sympathetic abnormalities included subnormal baseline norepinephrine levels, virtual absence of changes of norepinephrine levels during changes of arterial pressure, and supranormal pressor responses to phenylephrine infusions. Parasympathetic abnormalities included subnormal baseline standard deviations of R-R intervals, and R-R interval prolongations during elevations of arterial pressure which were unmistakably present, but subnormal. Our data suggest that in diabetic patients, subnormal baseline plasma norepinephrine levels may signify profound, possibly structural defects of sympathetic pathways. Subnormal resting levels of respiratory sinus arrhythmia may have different implications, however, since vagal, unlike sympathetic reflex abnormalities, can be reversed partly by arterial pressure elevations.
Induction of passive Heymann nephritis with antibodies specific for a synthetic peptide derived from the receptor-associated protein.
Authors: D Kerjaschki, R Ullrich, M Exner, R A Orlando, M G Farquhar
Journal: The Journal of Experimental Medicine (1996)

Passive Heymann nephritis (pHN) is an experimental rat model for human membranous glomerulopathy. In pHN, the formation of subepithelial immune deposits (ID) involves as antigenic targets the membrane glycoprotein gp330/megalin and the 44-kD receptor-associated protein (RAP). A single binding site for ID- inducing antibodies (Abs) was previously mapped to the 86 NH2-terminal amino acids of RAP (RAP1-86). To further narrow this epitope, Abs eluted from the glomeruli were immunoblotted on membranes that were loaded with overlapping synthetic peptides representing the amino acid sequence of RAP (SPOTs system). Two adjacent Ab-binding domains with the sequences PVRLAF, (amino acids 39-44) and HSD-LKIQE (amino acids 46-53), which were separated by a single L residue at amino acid 45, were detected. Rabbit Abs raised against synthetic peptides containing these domains individually (P31-44 and P46-53) failed to procedure glomerular IDs. By contrast, Abs raised against a larger composite peptide (P31-53) induced IDs within 3d that were firmly cross linked to the glomerular basement membrane. These data suggest that Ab binding in vivo depends on the conformation of the antigenic target sequence that is preserved in the synthetic peptide P31-53, which covers the entire Ab-binding domain of RAP but not in its subdomains, P31-44 and P46-53. Collectively, these results locate the sole ID-inducing epitope of RAP to amino acids 39-53.
Mitral Obstruction From Staphylococcal Endocarditis, Corrected Surgically
Authors: George Matula
Journal: JAMA (1975)

ALTHOUGH life-threatening hemodynamic abnormalities from valvular incompetence constitute a widely recognized complication of infective endocarditis, severe valvular obstruction by the vegetations characteristic of this disease has been reported infrequently,<sup>1,2</sup>and the diagnosis has usually been established at autopsy. Such obstruction may escape recognition since the clinical manifestations to which it gives rise can be suggestive of myocardial decompensation. In the patient described here, life-threatening mitral obstruction developed late in the course of staphylococcal endocarditis. Cardiac catheterization confirmed the diagnosis, and surgical correction was successful. <h3>Report of a Case</h3> A 51-year-old man was known to have rheumatic heart disease. In July 1973, his condition was categorized as cardiac class II, and his isolated mitral stenosis was judged to be moderate in degree and not to require surgical intervention. In late August 1973, the patient came to the Kaiser Foundation Hospital, San Francisco, with rigor and cough of 24 hours' duration.
Fat inhibition of gastric acid secretion in duodenal ulcer patients before and after proximal gastric vagotomy.
Authors: B Kihl, L Olbe
Journal: Gut (1980)

In seven duodenal ulcer patients the effect of intraduodenal infusion of 20 ml oleic acid on submaximal gastric acid secretion stimulation by a continuous pentagastrin infusion was evaluated before and after proximal gastric vagotomy. In the control tests 20 ml of saline was given. Before vagotomy, oleic acid evoked a significant inhibition of gastric acid secretion of 25% compared with the controls. This inhibition was abolished after proximal gastric vagotomy. The difference in inhibition before and after vagotomy was significant (P=0.01). It is concluded that the vagus nerve in man plays a decisive role in duodenal fat inhibition of gastric acid secretion.
Points from letters: Distinction awards
Authors: A H Mian
Journal: BMJ (1977)

should be deprived of benefit from their husbands' war service.Interest at 3-50o compound, without tax relief, payable to secure war service pension compares very unfavourably with the miserable 210O simple-taxable-paid since 1948 on our compensation for loss of goodwill.A colleague of mine with six years of war service recently wrote to the appropriate department of the Ministry of Defence seeking confirmation of the dates of his war service.I understand th'at the reply
Mast Cells in Small-Bowel Ulcers
Authors: Karl J. Shier
Journal: JAMA (1965)

<h3>To the Editor:—</h3> In reference to "Potassium-Induced Lesions of the Small Bowel," by Allen et al (<b>193</b>: 997, 1965)—several months before Baker's paper appeared inThe Journal(<b>190</b>:586, 1964), I, as a pathologist in a small general hospital, was faced with two cases of constricting circumferential smallbowel ulcers. Both surgical specimens were of identical gross and similar microscopic appearances. Both occurred in middle-aged white women with symptoms of chronic bowel obstruction. In examining multiple blocks I observed that, in some areas of the circumference, the lesion appeared less advanced or less intense than in others. The earlier lesions seemingly involved crypts of the mucosa. In addition, there was moderate epithelial hyperplasia at the edges of the narrow ulcers as well as striking eosinophilia in all sections. All three features, crypt involvement, epithelial hyperplasia, and eosinophilia, suggested a relation to ulcerative colitis. Further, mast cells were abundant in Giemsa preparations.
Acute Effects of Alpha-Methyldopa on Mean Blood Pressure and Plasma Renin Activity
Authors: PERRY V. HALUSHKA, HARRY R. KEISER
Journal: Circulation Research (1974)

α-Methyldopa significantly lowered mean blood pressure and plasma renin activity in dogs anesthetized with sodium pentobarbital. After unilateral ligation of the right renal vessels and contralateral denervation of the kidney, α-methyldopa significantly lowered mean blood pressure but did not change plasma renin activity. It was concluded that α-methyldopa acutely lowers plasma renin activity via an action mediated through the adrenergic nervous system. However, this decrease in plasma renin activity is not responsible for the decrease in mean blood pressure produced by the drug.
FIDELIS IMPLANTABLE DEFIBRILLATOR LEAD PERFORMANCE IN CHILDREN: DATA FROM THE INTERNATIONAL PEDIATRIC LEAD EXTRACTABILITY AND SURVIVAL EVALUATION (PLEASE) STUDY
Authors: Joseph Atallah, Vicki Freedenberg, Anne Dubin, Mitchell Cohen, Christopher Erickson, Ian Law, Bryan Cannon, Martin LaPage, Frank Cecchin, Terrence Chun, Charles Berul
Journal: Journal of the American College of Cardiology (2013)
Crippled clock hinders healing
Authors: Amy Maxmen
Journal: The Journal of Experimental Medicine (2009)

Diabetic eye damage may start in bone marrow, suggest [Busik and colleagues][1]. Damaged bone marrow nerves and disrupted circadian genes hampered the release of progenitor cells that are required to repair diabetes-induced vessel injury in the eye.

![Figure][2] 

Bone marrow nerves (arrows)