tbuckley/cabot-search huggingface dataset:
Functional heterogeneities among concanavalin A-activated OKT4+ and OKT8+ cells by using autologous erythrocyte rosette technique.
Authors: S Takada, Y Ueda, Y Murakawa, N Suzuki, T Sakane
Journal: Journal of Clinical Investigation (1983)

Normal human peripheral blood T lymphocytes activated by concanavalin A (Con A) were fractionated into OKT4+ and OKT8+ populations by complement-dependent cell lysis using OKT8 and OKT4 antibodies, respectively. By using the preferential ability of some, but not all, Con A-activated T cells to form rosettes with autologous erythrocytes, each population was further divided into autorosetting cells and nonautorosetting cells, and thus Con A-activated OKT4+ autorosetting, OKT4+ nonautorosetting, OKT8+ autorosetting, and OKT8+ nonautorosetting cells were obtained. The immune regulatory function of these populations was then investigated using a pokeweed mitogen-driven B cell plaque-forming cell system. These studies demonstrated that (a) autorosetting cells can exert potent suppressor activity regardless of their phenotypes of OKT4+ and OKT8+ antigens, and fail to help B cell differentiation; suppressor function mediated by these cells is radiosensitive; moreover, receptors for autologous erythrocytes may constitute either the interleukin 2 (IL2) receptors themselves or a component of an IL2 receptor-effector complex involved in modulating the growth signal that IL2 transmits to T cells; (b) OKT4+ nonrosetting cells serve adequately as radioresistant helper cells, but are devoid of suppressor cells; and (c) OKT8+ nonrosetting cells are found to lack either suppressor or helper activity, suggesting that they may belong to a T lymphocyte subset distinct from the subsets related to immune regulation. The results lead us, therefore, to the conclusion that there may exist functional heterogeneities among both the OKT4+ and OKT8+ populations; these heterogeneities can be dissected by virtue of the autologous erythrocyte rosette technique.
Asthma Severity and Exposure to Occupational Asthmogens
Authors: Nicole Le Moual, Valérie Siroux, Isabelle Pin, Francine Kauffmann, Susan M. Kennedy
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Severe asthma is a public health problem with limited information regarding preventable causes. Although occupational exposures have been implicated as important risk factors for asthma and asthma exacerbations, associations between occupational exposures and asthma severity have not been reported.To examine associations between occupational exposures and asthma severity.The Epidemiological Study on the Genetics and Environment of Asthma combines a case-control study with a family study of relatives of patients with asthma. Adult patients (n = 148) were recruited in chest clinics and control subjects without asthma (n = 228) were population-based. Occupational exposures to nonasthmogenic irritants and asthmogens (classified as "any asthmogen" including three broad groups: high-molecular-weight agents, low-molecular-weight agents, and mixed environments) were assessed by an asthma-specific job exposure matrix. Asthma severity was defined from an 8-grade clinical score (frequency of attacks, persistent symptoms, and hospitalization). Patients with severe (score >or= 2) and mild asthma were compared with control subjects using nominal logistic regression.Significant associations were observed between severe adult-onset asthma and exposure to any occupational asthmogen (odds ratio [OR], 4.0; 95% confidence interval [CI], 2.0-8.1), high-molecular-weight agents (OR, 3.7; CI, 1.3-11.1), low-molecular-weight agents (OR, 4.4; CI, 1.9-10.1), including industrial cleaning agents (OR, 7.2; CI, 1.3-39.9), and mixed environments (OR, 7.5; CI, 2.4-23.5). No significant associations were found between nonasthmogenic irritants and asthma severity, nor between asthmogens and childhood-onset asthma or mild adult-onset asthma.Our results suggested a strong deleterious role of occupational asthmogens in severe asthma. Clinicians should consider occupational exposures in patients with moderate to severe asthma.
Infantile Metachromatic Leukodystrophy
Authors: Jules G. Leroy, August F. Van Elsen, Jean-Jacques Martin, Jan E. Dumon, André E. Hulet, Shintaro Okada, Carmen Navarro
Journal: New England Journal of Medicine (1973)

Infantile metachromatic leukodystrophy was diagnosed in utero by the absence of arylsulfatase A in cultured amniotic-fluid cells. The diagnosis was confirmed since enzyme activity was not demonstrable in cultured fetal skin fibroblasts, liver, or brain, and since characteristic histologic metachromatic deposits were present in kidney. Electron microscopy showed abnormal cytoplasmic membrane-bound inclusions, composed in part of stacked lamellar structures, in renal tubular cells and in Schwann and endoneurial cells of the sciatic nerve. Intrauterine diagnosis of metachromatic leukodystrophy is thus a potentially valuable method. (N Engl J Med 288:1365–1369, 1973)
ET-38 * BRAIN PENETRATING NON-VIRAL GENE VECTORS FOR EFFICIENT GENE TRANSFER TO BRAIN TUMORS
Authors: P. Mastorakos, C. Zhang, S. Berry, A. Kim, G. Woodworth, J. S. Suk, J. Hanes
Journal: Neuro-Oncology (2014)

Gene therapy constitutes an attractive approach for curing a variety of CNS diseases, including glioblastoma. Multiple studies have been carried out focusing on improving the total level and distribution of gene expression throughout the brain tissue. Viral gene delivery, though relatively efficient, has been limited by immunogenicity, low packaging capacity and difficulties in scale-up. Non-viral gene vectors offer an alternative strategy but are limited in their ability to generate high-level, widespread therapeutic effect. The nanoporous and electrostatically charged extracellular space found between healthy or tumor cells constitutes a steric and adhesive barrier, which hampers widespread distribution of gene vectors in the brain, regardless of administration method, thereby limiting gene transfer to target cells [1]. Indeed, following convention enhanced delivery (CED) conventional gene vectors are confined to the point of administration, limiting the clinical success of gene therapy for glioblastoma [2]. We developed a strategy to formulate small, stable and densely coated cationic polymer-based gene vectors that have the physicochemical characteristics required to overcome this ‘brain tissue barrier’. Using high resolution multiple particle tracking, we assessed the diffusion rates of gene vectors in freshly extracted ex vivo healthy and tumor rodent brain tissues. We thoroughly characterized their toxicity, cell uptake and transfection efficacy in vitro. Finally, we analyzed the ability of these vectors to rapidly penetrate and distribute throughout the brain tissue in vivo, thus reaching and transfecting cells over a large volume following CED. 1.Nance, E.A., et al., Sci Transl Med, 2012. 2.Voges, J., et al., Ann Neurol, 2003.
Two types of object representations in the brain, one nondescriptive process of reference fixing
Authors: Athanassios Raftopoulos
Journal: Behavioral and Brain Sciences (2004)

I comment on two problems in Glover's account. First, semantic representations are not always available to awareness. Second, some functional properties, the affordances of objects, should be encoded in the dorsal system. Then I argue that the existence of Glover's two types of representations is supported by studies on “object-centered” attention. Furthermore, it foreshadows a nondescriptive causal reference fixing process.
Abstract 3283: VB-111 a novel anti-angiogenic vector and a promising treatment for metastatic cancer in combination with other anticancer drugs
Authors: Eyal Breitbart, Yael C. Cohen, Livnat Bangio
Journal: Cancer Research (2011)

Abstract Background: VB-111 is a vascular disruptive and anti-angiogenic agent consisting of a non-replicating adenovirus vector (Ad-5, E1 deleted), which contains a novel Vascular Targeting System™, VTS™, and a fas and human tumor necrosis factor receptor chimeric transgene. This modified promoter specifically expresses the fas chimera transgene in tumor vessel endothelium, leading to targeted apoptosis. Preclinical in vitro and in vivo studies as well as a phase I clinical trial, have shown that VB-111 was safe and well tolerated, and had significant antitumor activity. We report here the results of a comprehensive set of in vivo studies of VB-111 in combination with chemotherapeutic and anti-angiogenic drugs. Methods: The safety and efficacy of VB-111 were evaluated employing the Lewis Lung metastasis model as a monotherapy, in combination with bevacizumab and in combination with Paclitaxel. Results: VB-111 was found to induce a dose dependent reduction of up to 90% in tumor burden of lung metastases in Lewis Lung metastasis model. Evaluation of the combined therapy with VB-111 and Avastin in Lewis Lung metastasis model showed no additive effect of Avastin 4 or 8 mg/kg as compared to VB-111 as a monotherapy. Additive effect was seen when mice were treated with a lower dose of VB-111 (1×10E9 VP/mouse) in combination with Paclitaxel (40mg/kg) and with higher dose of VB-111 (1×10E11 VP/mouse) with Paclitaxel (20mg/kg). No toxicity was observed as a result of the combined therapy, except for the lungs the organ weights among the different treatment groups showed minimal variation. In all the mice tested, the harvested organs were found to have normal growth pathology with no lesions or evidence of metastasis. Monotherapy with VB-111 did not result in any toxicity and combination therapy did not introduce additional toxicities. Conclusions: As previously shown, VB-111 was found to be safe and specific. VB-111 may provide additive effect to chemotherapy in a combination regimen. This will be further explored in clinical trials. 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 3283. doi:10.1158/1538-7445.AM2011-3283
Assessing Faculty Financial Relationships With Industry
Authors: Elizabeth A. Boyd, Lisa A. Bero
Journal: JAMA (2000)

A growing number of academic researchers receive industry funding for clinical and basic research, but little is known about the personal financial relationships of researchers with their industry sponsors.To assess the extent to which faculty researchers have personal financial relationships with the sponsors of their research, the nature of those financial relationships, and efforts made at the institutional level to address disclosed financial relationships and perceived conflicts of interest.Case study of the University of California, San Francisco (UCSF). Data sources included disclosure forms and official documents maintained by the UCSF Office of Research Administration from December 1980 to October 1999, including decisions made by the UCSF Chancellor's Advisory Panel on Relations with Industry.Number and types of personal financial relationships with external sponsors (positive financial disclosures from all clinical, basic, or social science faculty who were principal investigators), amount of annual income received from sponsors, and decisions and management strategies used by the advisory panel.By 1999, almost 7.6% of faculty investigators reported personal financial ties with sponsors of their research. Throughout the study period, 34% of disclosed relationships involved paid speaking engagements (range, $250-$20, 000 per year), 33% involved consulting agreements between researcher and sponsor (range, <$1000-$120,000 per year), and 32% involved the investigator holding a position on a scientific advisory board or board of directors. Fourteen percent involved equity ownership, and 12% involved multiple relationships. The advisory panel recommended managing perceived conflicts of interest in 26% of the cases, including recommending the sale of stock, refusing additional payment for talks, resigning from a management position, or naming a new principal investigator for a project.Faculty researchers are increasingly involved in financial relationships with their research sponsors. Guidelines for what constitutes a conflict and how the conflict should be managed are needed if researchers are to have consistent standards of behavior among institutions. JAMA. 2000;284:2209-2214.
Diffuse Pancreatic Ga-67 Uptake in Pancreatitis With Markedly Elevated Ca 19-9 Tumor Marker
Authors: USHA A. JOSEPH, SATISH G. JHINGRAN, JOHN C. McKECHNIE
Journal: Clinical Nuclear Medicine (1996)

A 73-year-old woman, who was nonethanolic, experienced recent onset of right upper abdominal pain, fever, obstructive jaundice with normal serum amylase, elevated liver function test results, and markedly elevated Ca 19-9 tumor marker. Abdominal CT scan showed diffusely enlarged pancreas with a questionable mass in the pancreatic head. Ga-67 imaging showed persistent marked diffuse pancreatic uptake on 24-hour and 96-hour scans. Exploratory laparotomy and cholecystoje-junostomy for obstructive jaundice with transduodenal biopsies from four different areas of diffusely enlarged, hard pancreas revealed acute and chronic pancreatitis and fibrosis, but no malignancy. The patient was in good health 3 years after surgery. In such situations, diffuse pancreatic uptake of Ga-67 can help strengthen diagnosis of pancreatitis over pancreatic cancer, despite normal amylase and high tumor marker levels.
CLINICAL UTILITY OF THE LEVEL OF PLASMA BRAIN NATRIURETIC PEPTIDE IN TETRALOGY OF FALLOT PATIENTS LONG-TERM AFTER INITIAL INTRACARDIAC REPAIR: CONSIDERATION FOR PULMONARY VALVE REPLACEMENT
Authors: Atsushi Kitagawa, Takashi Honda, Sumito Kimura, Kagami Miyaji
Journal: Journal of the American College of Cardiology (2014)
TCT-68 Does IVUS Reduce Stent Thrombosis with DES? Two-year results from the prospective, multicenter ADAPT-DES study
Authors: Akiko Maehara, Giora Weisz, Franz-Josef Neumann, D. Christopher Metzger, Timothy D. Henry, David Cox, Peter L. Duffy, Bruce R. Brodie, Thomas Stuckey, Ernest L. Mazzaferri, Ke Xu, Roxana Mehran, Helen Parise, Gary S. Mintz, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2013)
Abstract S1-6: Results of a randomized phase 2 study of PD 0332991, a cyclin-dependent kinase (CDK) 4/6 inhibitor, in combination with letrozole vs letrozole alone for first-line treatment of ER+/HER2− advanced breast cancer (BC)
Authors: RS Finn, JP Crown, I Lang, K Boer, IM Bondarenko, SO Kulyk, J Ettl, R Patel, T Pinter, M Schmidt, Y Shparyk, AR Thummala, NL Voytko, A Breazna, ST Kim, S Randolph, DJ Slamon
Journal: Cancer Research (2012)

Abstract Background: PD 0332991, a selective inhibitor of CDK 4/6, prevents cellular DNA synthesis by blocking cell cycle progression. Preclinical studies in a BC cell line panel identified the luminal ER subtype, elevated expression of cyclin D1 and Rb protein, and reduced p16 expression as being associated with sensitivity to PD 0332991 (Finn et al. 2009). Synergistic activity was also observed in vitro when combined with tamoxifen. After determination of the recommended phase 2 dose in combination with letrozole (letrozole 2.5 mg QD plus PD 0332991 125 mg QD on Schedule 3/1), a randomized phase 2 study comparing letrozole alone (L) to letrozole plus PD 0332991 (L+P) was initiated. Methods: The phase 2 portion of the study was designed as a two-part study; Part 1 enrolled post- menopausal women with ER+/HER2− advanced BC; Part 2 in addition to ER+/HER2− as eligibility criteria, screened for CCND1 amplification and/or loss of p16 by FISH. The primary endpoint is progression-free survival (PFS); secondary endpoints include response rate, overall survival, safety, and correlative biomarker studies. In both parts, post-menopausal women with ER+/HER2− advanced BC were randomized 1:1 to receive letrozole either with or without PD 0332991. Pts continue on assigned study treatment until disease progression, unacceptable toxicity, or consent withdrawal, and are followed for tumor assessments every 2 months. Results: 66 pts were randomized in Part 1 and 99 pts in Part 2. Preliminary results from Part 1 of this study have been previously reported (IMPAKT Breast Cancer Conference, Abstract #292, Finn et al. May 2012) demonstrating a significant improvement in median PFS in the L+P vs. L arm (HR = 0.35; 95% CI, 0.17 to 0.72; p = 0.006). With the additional 99 pts randomized in Part 2 (N = 165), the statistically significant improvement in median PFS (26.2 vs. 7.5 months, respectively) continues to be observed with a HR=0.32 (95% CI, 0.19 to 0.56) with p &amp;lt;0.001. The response rate for the L+P arm (n = 84) was 31% vs. 26% for the L arm (n = 81) and the clinical benefit rate was 68% vs. 44%, respectively. The most commonly reported treatment-related AEs in the combination arm were neutropenia, leukopenia, anemia, and fatigue. The updated results from the combined Part 1 and Part 2 group will be presented in December 2012. Conclusions: The combination of PD 0332991 and letrozole is well tolerated and shows encouraging clinical benefit, confirming the sensitivity of ER+ BC to PD 0332991 observed in preclinical models. A phase 3 trial in this setting will commence in 2013. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S1-6.
Child resistant containers for liquid medications.
Authors: R W Odd
Journal: BMJ (1993)

was also considerably less, with 37 of 40 (93%) patients having no postoperative discomfort and being able to return to school soon after surgery compared with 16 of 35 (46%) who were circum- cised.Twenty eight of 40 responding parents whose son had had preputial plasty thought that the final appearance of their son's penis was normal.Only two patients were unable to retract their foreskins, and in both there had been no effort at early mobilisation.Preputial plasty is a well recognised procedure in Europe,4 and we think that it is a reliable option for selected patients with tight but unscarred and uninfected foreskins.It certainly enables many more foreskins to be saved.
Allergen-induced airway remodelling
Authors: C. M. Lloyd, D. S. Robinson
Journal: European Respiratory Journal (2007)

Airway remodelling is associated with chronic asthma but it remains unclear whether it results from airway inflammation in response to allergens or immune-mediated events such as viral infections. Although the acute inflammation associated with asthma has been modelled extensively both in vitro and in vivo , the structural changes occurring in the lung have only recently been investigated. These in vitro , in vivo and in silico systems have been designed to examine the pathways leading to allergen-induced airway remodelling and have enabled investigators to draw conclusions about the participation of key cells and molecules in the development of allergen-induced airway remodelling. However, fundamental questions remain regarding the genesis of remodelling as well as the relationship between functional symptoms and pathological changes that occur. In this review the key questions relating allergen exposure to development of remodelling are discussed, as well as the steps that are being undertaken to investigate them.
Airway anesthesia and respiratory adaptations to dead space loading and exercise.
Authors: B S Krishnan, M J Stockwell, R E Clemens, C G Gallagher
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

In exercising humans, added external dead space (VD) increases minute ventilation (VI) and causes a slower and deeper breathing pattern (J. Appl. Physiol. 1991; 70:55-62). Recent studies suggest that airway receptors sensitive to topical anesthesia influence VI and breathing pattern responses to exercise and to added VD. We tested these hypotheses with a technique of airway anesthesia (Anesthesia) that has been shown to reliably attenuate airway reflexes. Anesthesia was administered by local laryngopharyngeal application and aerosolized lidocaine inhalation, and was confirmed by citric acid aerosol inhalation challenges. Twelve normal males performed maximal incremental cycle ergometer exercise on 4 d (randomized) after Anesthesia with (Anesthesia VD) and without added VD (Anesthesia Control) and after normal saline inhalation (Saline) with (Saline VD) and without added VD (Saline Control). There were no differences in the VI and breathing pattern responses during exercise between the Saline Control and the Anesthesia Control tests. After both Saline and Anesthesia inhalation, added VD resulted in an increase in VI both at rest and during exercise. At matched VI (98 L/min), the differences in tidal volume (VT) between the Saline Control and Saline VD tests (delta = 0.23 +/- 0.24 L, mean +/- SD) and the Anesthesia Control and Anesthesia VD tests (delta = 0.20 +/- 0.28 L) were not significantly different. Our study had a power of greater than 95% to detect significant differences in VI or breathing pattern due to Anesthesia. We conclude that in normal humans, airway receptors do not play a major role in ventilation and breathing pattern control during exercise, and that the respiratory adaptations to added VD during exercise are not mediated by airway afferent reflexes.
Acute High-Altitude Illness in Mountaineers and Problems of Rescue
Authors: RODMAN WILSON
Journal: Annals of Internal Medicine (1973)

Syndromes of acute mountain sickness share hypoxia as a cause, but expression of the illness varies. Cerebral edema is a cause for the development of headache, selective neurologic defect, and coma and perhaps even for high-altitude pulmonary edema, although microthrombi in pulmonary capillaries are often seen in the latter and may be causal. Retinal and preretinal hemorrhages frequently occur at high altitude. Acute mountain sickness is difficult to treat on a mountain, even with oxygen. Drugs are of uncertain usefulness; therefore immediate attempts to lower a victim are in order. Rescue by air is best, but it is hazardous to leave unacclimatized rescuers above 2400 m [8000 feet] without oxygen and the assistance of a ground party. The features of acute mountain sickness and principles of rescue are discussed.
Plasma Exosomes Protect the Myocardium From Ischemia-Reperfusion Injury
Authors: Jose M. Vicencio, Derek M. Yellon, Vivek Sivaraman, Debashish Das, Claire Boi-Doku, Sapna Arjun, Ying Zheng, Jaime A. Riquelme, Jessica Kearney, Vikram Sharma, Gabriele Multhoff, Andrew R. Hall, Sean M. Davidson
Journal: Journal of the American College of Cardiology (2015)