tbuckley/cabot-search huggingface dataset:
Differences between human embryonic stem cell lines
Authors: C. Allegrucci, L.E. Young
Journal: Human Reproduction Update (2006)

The promise of human embryonic stem cell (hESC) lines for treating injuries and degenerative diseases, for understanding early human development, for disease modelling and for drug discovery, has brought much excitement to scientific communities as well as to the public. Although all of the lines derived worldwide share the expression of characteristic pluripotency markers, many differences are emerging between lines that may be more associated with the wide range of culture conditions in current use than the inherent genetic variation of the embryos from which embryonic stem cells were derived. Thus, the validity of many comparisons between lines published thus far is difficult to interpret. This article reviews the evidence for differences between lines, focusing on studies of pluripotency marker molecules, transcriptional profiling, genetic stability and epigenetic stability, for which there is most evidence. Recognition and assessment of environmentally induced differences will be important to facilitate the development of culture systems that maximize stability in culture and provide lines with maximal potential for safety and success in the range of possible applications.
H<sub>2</sub> Antihistamines (Cimetidine) and Allergic‐Inflammatory Reactions
Authors: Svend Norn, Henrik Permin, Per Stahl Skov
Journal: Allergy (1980)

Experiments in the skin and synovialis have thrown new light on the allergic-inflammatory reactions. The inflammatory effect of histamine is thus due to stimulation of two different types of receptors in the vessels, i.e. histaminergic H1 and H2 receptors. Both types of receptors are of importance for the immediate cutaneous response to allergens and histamine. Treatment with a combination of H1 antagonists (classical antihistamines) and the H2 antagonist cimetidine will thus cause a much stronger inhibition of the urticarial reactions than treatment with the H1 and H2 antagonist alone. It is therefore probable that a combination therapy could have an advantage over the traditional treatment with classical antihistamines in urticaria and other histamine-mediated skin diseases. Histamine might also be of importance for the swelling of the joints in inflammatory diseases such as rheumatoid arthritis, and clinical trials with H1 and H2 antagonists are in progress.
Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men
Authors: Milena Bogunovic, Florent Ginhoux, Amy Wagers, Martine Loubeau, Luis M. Isola, Lauren Lubrano, Vesna Najfeld, Robert G. Phelps, Celia Grosskreutz, Eilleen Scigliano, Paul S. Frenette, Miriam Merad
Journal: The Journal of Experimental Medicine (2006)

In this study, we explored dermal dendritic cell (DC) homeostasis in mice and humans both in the steady state and after hematopoietic cell transplantation. We discovered that dermal DCs proliferate in situ in mice and human quiescent dermis. In parabiotic mice with separate organs but shared blood circulation, the majority of dermal DCs failed to be replaced by circulating precursors for &amp;gt;6 mo. In lethally irradiated mice injected with donor congenic bone marrow (BM) cells, a subset of recipient DCs remained in the dermis and proliferated locally throughout life. Consistent with these findings, a large proportion of recipient dermal DCs remained in patients' skin after allogeneic hematopoietic cell transplantation, despite complete donor BM chimerism. Collectively, our results oppose the traditional view that DCs are nondividing terminally differentiated cells maintained by circulating precursors and support the new paradigm that tissue DCs have local proliferative properties that control their homeostasis in the steady state. Given the role of residual host tissue DCs in transplant immune reactions, these results suggest that dermal DC homeostasis may contribute to the development of cutaneous graft-versus-host disease in clinical transplantation.
Hypoxia and the neonatal rabbit lung: neuroendocrine cell numbers, 5-HT fluorescence intensity, and the relationship to arterial thickness.
Authors: I M Keith, J A Will
Journal: Thorax (1981)

We assessed the dynamics of neuroendocrine (NE) cell numbers, the intensity of specific 5-HT fluorescence, and the arterial medial thickness in the lungs of neonatal rabbits in normoxia and acute and chronic hypoxia. Hypoxic neonates had significantly higher NE cell numbers and medial thickness of the pulmonary arteries at 5 days of age than did normoxic controls; 1- and 3-day-old young that died in hypoxia also had significantly higher cell numbers and medial thickness than did hypoxic survivors. A decline in these cell numbers was noted between 1 and 5 days of age among normoxic young, whereas there was no significant change among hypoxic young. Medial thickness was unchanged among normoxic young but increased between 1 and 5 days of age among hypoxic survivors. A 1-day exposure to normoxia of hypoxic young four days postpartum caused a decrease in NE cell numbers and medial thickness to more normal values. Serotonin (5-HT) fluorescence intensity levels of groups of NE cells or neuroepithelial bodies (NEBs) in this group were equal to those of normal controls although these levels were decreased in early chronic hypoxia. Medial thickness and NE cell numbers were inversely correlated with serotonin levels, suggesting that serotonin may be associated with medial hypertrophy and presence of argyrophil material. Medial thickness was positively correlated with NE cell numbers. The above findings led to the following summary: pulmonary NE cells respond to changes in airway oxygen levels; hypoxia or decreased oxygen is associated with decreased cellular 5-HT content and an increase in NE cell numbers by argyrophil stain and medial thickness of pulmonary artery walls. The change to normoxia from hypoxia results in higher cellular 5-HT content and decreased NE argyrophil cell numbers along with reduced pulmonary artery wall medial thickness.
Rebuilding Human Leukocyte Antigen Class II–Restricted Minor Histocompatibility Antigen Specificity in Recall Antigen-Specific T Cells by Adoptive T Cell Receptor Transfer: Implications for Adoptive Immunotherapy
Authors: Robbert Spaapen, Kelly van den Oudenalder, Roman Ivanov, Andries Bloem, Henk Lokhorst, Tuna Mutis
Journal: Clinical Cancer Research (2007)

Donor T cells directed to hematopoietic minor histocompatibility antigens (mHag) are appealing tools for adoptive immunotherapy of hematological malignancies after allogeneic stem cell transplantation (allo-SCT). Toward the development of a convenient strategy for ex vivo generation of human leukocyte antigen (HLA) class II--restricted mHag-specific T cells, we evaluated the feasibility of rebuilding mHag-specific T cell functions in donor-derived recall antigen-specific T cells via T cell receptor (TCR) transfer.TCR alpha- and beta-chains of an HLA-DPB1*0401--restricted T-cell clone recognizing a multiple myeloma-associated mHag were retrovirally transferred into a tetanus toxoid (TT)--specific clone derived from the original stem cell donor. TCR double-transduced cells were compared with the parent mHag- and TT-specific clones for antigen specificity, cytokine secretion, and cytotoxic activity and were analyzed for their in vitro expansion capacity in a TT- or mHag-specific fashion.mHag-TCR--transduced TT-specific cells displayed both TT and mHag specificity. Similar to the parent cells, they secreted Th-1 cytokines and exerted significant cytotoxic activity against TT-pulsed or mHag(+) target cells, including multiple myeloma cells. A 4-week expansion of TCR-transduced cells via the TT-specific TCR had no negative influence on the mHag-specific cytotoxic activity and resulted in 10- to 100-fold better cell yields as compared with mHag-specific expansion.HLA class II--restricted, mHag-specific effector functions can be successfully reconstructed in donor-derived TT-specific T cells via TCR transfer. Effective expansion of these T cells via TT-specific TCRs illustrate the suitability of this strategy for ex vivo expansion and possibly for in vivo TT-specific reboosting of HLA class II--restricted immunotherapeutic T cells.
Some hazards of lithium use
Authors: J W Jefferson, J H Greist
Journal: American Journal of Psychiatry (1981)

The increasingly widespread use of lithium has benefited many, but the therapeutic potential of the drug will not be realized if it is used in a way that is haphazard or inattentive or adheres too rigidly to written guidelines. The authors present clinical vignettes that are representative rather than comprehensive examples of misadventures which can occur during the course of lithium therapy. They hope to stimulate a more knowledgeable, flexible, open-minded, and individualized approach to the use of this drug.
Coronary Vasomotor Abnormalities in Insulin-Resistant Individuals
Authors: Manuel J. Quiñones, Miguel Hernandez-Pampaloni, Heinrich Schelbert, Isabel Bulnes-Enriquez, Xochitl Jimenez, Gustavo Hernandez, Roxana De La Rosa, Yun Chon, Huiying Yang, Susanne B. Nicholas, Tamara Modilevsky, Katherine Yu, Katja Van Herle, Lawrence W. Castellani, Robert Elashoff, Willa A. Hsueh
Journal: Annals of Internal Medicine (2004)

Background: Insulin resistance is a metabolic spectrum that progresses from hyperinsulinemia to the metabolic syndrome, impaired glucose tolerance, and finally type 2 diabetes mellitus. It is unclear when vascular abnormalities begin in this spectrum of metabolic effects. Objective: To evaluate the association of insulin resistance with the presence and reversibility of coronary vasomotor abnormalities in young adults at low cardiovascular risk. Design: Cross-sectional study followed by prospective, open-label treatment study. Setting: University hospital. Patients: 50 insulin-resistant and 22 insulin-sensitive, age-matched Mexican-American participants without glucose intolerance or traditional risk factors for or evidence of coronary artery disease. Intervention: 3 months of thiazolidinedione therapy for 25 insulin-resistant patients. Measurements: Glucose infusion rate in response to insulin infusion was used to define insulin resistance (glucose infusion rate ≤ 4.00 mg/kg of body weight per minute [range, 0.90 to 3.96 mg/kg per minute]) and insulin sensitivity (glucose infusion rate ≥ 7.50 mg/kg per minute [range, 7.52 to 13.92 mg/kg per minute]). Myocardial blood flow was measured by using positron emission tomography at rest, during cold pressor test (largely endothelium-dependent), and after dipyridamole administration (largely vascular smooth muscle–dependent). Results: Myocardial blood flow responses to dipyridamole were similar in the insulin-sensitive and insulin-resistant groups. However, myocardial blood flow response to cold pressor test increased by 47.6% from resting values in insulin-sensitive patients and by 14.4% in insulin-resistant patients. During thiazolidinedione therapy in a subgroup of insulin-resistant patients, insulin sensitivity improved, fasting plasma insulin levels decreased, and myocardial blood flow responses to cold pressor test normalized. Limitations: The study was not randomized, and it included only 1 ethnic group. Conclusions: Insulin-resistant patients who do not have hypercholesterolemia or hypertension and do not smoke manifest coronary vasomotor abnormalities. Insulin-sensitizing thiazolidinedione therapy normalized these abnormalities. These results suggest an association between insulin resistance and abnormal coronary vasomotor function, a relationship that requires confirmation in larger studies.
Central Dopamine Receptors Regulate Blood Eosinophilia in the Rat
Authors: Z. Podolec, J. Vetulani, B. Bednarczyk, A. Szczeklik
Journal: Allergy (1979)

Dopaminergic agents, dopa and apomorphine, affected biphasically the blood eosinophil count in the rat: low doses of the drug elevated, while high doses lowered it. The response to a high dose of dopa was retained in rats pretreated with an inhibitor of dopamine-beta-hydroxylase, U 10, 157, but prevented by a centrally acting dopa decarboxylase inhibitor, NSD 1015. This indicates that the eosinopenia observed after large doses of dopa is due to the action of dopamine formed from the precursor. As intracerebroventricular injections of Ldopa also produce eosinopenia, the central site of dopamine action is indicated. The eosinopenic response to apomorphine was antagonized by a dopamine receptor blocking agent, haloperidol. This indicates that some central dopamine receptors are involved in the regulation of the eosinophil count in circulating blood. The hypophysis seems to play a crucial role in the phenomenon observed, as no eosinopenia was produced by dopa in hypophysectomized rats.
Magnetic resonance colonography without bowel cleansing: a prospective cross sectional study in a screening population
Authors: C. A Kuehle, J. Langhorst, S. C Ladd, T. Zoepf, M. Nuefer, F. Grabellus, J. Barkhausen, G. Gerken, T. C Lauenstein
Journal: Gut (2007)

To evaluate the diagnostic accuracy of magnetic resonance colonography (MRC) without bowel cleansing in a screening population and compare the results to colonoscopy as a standard of reference.315 screening patients, older than 50 years with a normal risk profile for colorectal cancer, were included in this study. For MRC, a tagging agent (5.0% Gastrografin, 1.0% barium sulphate, 0.2% locust bean gum) was ingested with each main meal within 2 days prior to MRC. No bowel cleansing was applied. For the magnetic resonance examination, a rectal water enema was administered. Data collection was based on contrast enhanced T1 weighted images and TrueFISP images. Magnetic resonance data were analysed for image quality and the presence of colorectal lesions. Conventional colonoscopy and histopathological samples served as reference.In 4% of all colonic segments, magnetic resonance image quality was insufficient because of untagged faecal material. Adenomatous polyps >5 mm were detected by means of MRC, with a sensitivity of 83.0%. Overall specificity was 90.2% (false positive findings in 19 patients). However, only 16 of 153 lesions <5 mm and 9 of 127 hyperplastic polyps could be visualised on magnetic resonance images.Faecal tagging MRC is applicable for screening purposes. It provides good accuracy for the detection of relevant (ie, adenomatous) colorectal lesions >5 mm in a screening population. However, refinements to optimise image quality of faecal tagging are needed.
Impact of Age at Diagnosis on Prostate Cancer Treatment and Survival
Authors: Seth K. Bechis, Peter R. Carroll, Matthew R. Cooperberg
Journal: Journal of Clinical Oncology (2010)

Purpose Older men are more likely to be diagnosed with high-risk prostate cancer and to have lower overall survival. As a result, age often plays a role in treatment choice. However, the relationships among age, disease risk, and prostate cancer–specific survival have not been well established. Patients and Methods We studied men in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database with complete risk, treatment, and follow-up information. High-risk patients were identified by using the validated Cancer of the Prostate Risk Assessment (CAPRA) score. Competing risks regression was used to identify the independent impact of age on cancer-specific survival. We also analyzed the effect of local treatment on survival among older men with high-risk disease. Results In all, 26% of men age ≥ 75 years presented with high-risk disease (CAPRA score 6 to 10). Treatment varied markedly with age across risk strata; older men were more likely to receive androgen deprivation monotherapy. Controlling for treatment modality alone, or for treatment and risk, age did not independently predict cancer-specific survival. Furthermore, controlling for age, comorbidity, and risk, older men with high-risk tumors receiving local therapy had a 46% reduction in mortality compared with those treated conservatively. Conclusion Older patients are more likely to have high-risk prostate cancer at diagnosis and less likely to receive local therapy. Indeed, underuse of potentially curative local therapy among older men with high-risk disease may in part explain observed differences in cancer-specific survival across age strata. These findings support making decisions regarding treatment on the basis of disease risk and life expectancy rather than on chronologic age.
Distal Microcirculatory Protection During Percutaneous Coronary Intervention in Acute ST-Segment Elevation Myocardial Infarction&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Gregg W. Stone
Journal: JAMA (2005)

Atheromatous and thrombotic embolization during percutaneous coronary intervention (PCI) in acute myocardial infarction is common and may result in microcirculatory dysfunction, the prevention of which may improve reperfusion success, reduce infarct size, and enhance event-free survival.To determine whether protection of the distal microcirculation from thromboembolic debris liberated during primary PCI results in improved reperfusion and decreased infarct size.Prospective randomized controlled trial at 38 academic and community-based institutions in 7 countries enrolling 501 patients aged 18 years or older with ST-segment elevation myocardial infarction (STEMI) presenting within 6 hours of symptom onset and undergoing primary PCI or rescue intervention after failed thrombolysis.Patients were randomized between May 20, 2002, and November 21, 2003, to receive PCI with a balloon occlusion and aspiration distal microcirculatory protection system vs angioplasty without distal protection.Coprimary end points were ST-segment resolution (STR) measured 30 minutes after PCI by continuous Holter monitoring and infarct size measured by technetium Tc 99m sestamibi imaging between days 5 and 14. Secondary end points included major adverse cardiac events.Among 252 patients assigned to distal protection, aspiration was performed in 97% (242/251), all angioplasty balloon inflations were fully protected in 79% (193/245), and visible debris was retrieved from 73% (182/250). Complete STR was achieved in a similar proportion reperfused with vs without distal protection (63.3% [152/240] vs 61.9% [148/239], respectively; absolute difference, 1.4% [95% confidence interval, -7.7% to 10.5%; P = .78]), and left ventricular infarct size was similar in both groups (median, 12.0% [n = 229] vs 9.5% [n = 208], respectively; P = .15). Major adverse cardiac events at 6 months occurred with similar frequency in the distal protection and control groups (10.0% vs 11.0%, respectively; P = .66).A distal balloon occlusion and aspiration system effectively retrieves embolic debris in most patients with acute STEMI undergoing emergent PCI. Nonetheless, distal embolic protection did not result in improved microvascular flow, greater reperfusion success, reduced infarct size, or enhanced event-free survival.
A pilot approach for quantitative assessment of liver fibrosis using ultrasound: preliminary results in 79 cases
Authors: Hiroyuki Yamada, Masaaki Ebara, Tadashi Yamaguchi, Shinichirou Okabe, Hiroyuki Fukuda, Masaharu Yoshikawa, Takashi Kishimoto, Hisahiro Matsubara, Hiroyuki Hachiya, Hiroshi Ishikura, Hiromitsu Saisho
Journal: Journal of Hepatology (2005)
Clinical Examination Following Preoperative Chemoradiation for Rectal Cancer Is Not a Reliable Surrogate End Point
Authors: Jose G. Guillem, David B. Chessin, Jinru Shia, Harvey G. Moore, Madhu Mazumdar, Bianca Bernard, Philip B. Paty, Leonard Saltz, Bruce D. Minsky, Martin R. Weiser, Larissa K.F. Temple, Alfred M. Cohen, W. Douglas Wong
Journal: Journal of Clinical Oncology (2005)

Clinical assessment of rectal cancer response to preoperative combined-modality therapy (CMT) using digital rectal examination (DRE) has been proposed as a means of assessing efficacy of therapy. However, because the accuracy of this approach has not been established, we conducted a prospective analysis to determine the operating surgeon's ability to assess response using DRE.Ninety-four prospectively accrued patients with locally advanced rectal cancer (T3/4 or N1) were evaluated with DRE and sigmoidoscopy in order to determine the following tumor characteristics: size, location, mobility, morphology, and circumference. Following preoperative CMT (50.40 Gy with fluorouracil-based chemotherapy) and under general anesthesia, the same surgeon estimated tumor response based on changes in these tumor characteristics, assessed via DRE. Percent pathologic tumor response was determined prospectively by a single pathologist using whole mount sections of the resected cancer.Clinical assessment using DRE underestimated pathologic response in 73 cases (78%). In addition, DRE was able to identify only 3 of 14 cases (21%) with a pathologic complete response. There were no clinical overestimates of response. None of the clinicopathologic tumor characteristics examined had a significant impact on DRE estimation of response.Clinical examination underestimates the extent of rectal cancer response to preoperative CMT. Given the inaccuracy of DRE following preoperative CMT, it should not be used as a sole means of assessing efficacy of therapy nor for selecting patients following CMT for local surgical therapies.
Intramyocardial Fibroblast Myocyte Communication
Authors: Rahul Kakkar, Richard T. Lee
Journal: Circulation Research (2010)

Cardiac fibroblasts are emerging as key components of normal cardiac function, as well as the response to stressors and injury. These most numerous cells of the heart interact with myocytes via paracrine mechanisms, alterations in extracellular matrix homeostasis, and direct cell-cell interactions. It is possible that they are a contributor to the inability of adult myocytes to proliferate and may influence cardiac progenitor biology. Furthering our understanding of how cardiac fibroblasts and myocytes interact may provide an avenue to novel treatments for heart failure prevention. This review discusses the most recent concepts in cardiac fibroblast-myocyte communication and areas of potential future research.
Utility of Fine-Needle Aspiration As a Diagnostic Technique in Lymphoma
Authors: Sean T. Hehn, Thomas M. Grogan, Thomas P. Miller
Journal: Journal of Clinical Oncology (2004)

To evaluate, from a clinician's perspective, the sensitivity and specificity of fine-needle aspiration (FNA) as a technique for the diagnosis of lymphoma.Medical records of 470 new patients seen in one lymphoma specialist's clinic from January 1998 through December 2002 were reviewed. Ninety-nine (21%) of the 470 patients underwent a total of 115 FNA procedures, which were assessed by more than 70 different pathologists in 32 different pathology departments. Subsequent excisional biopsies were performed in 67 of these patients and interpreted by a single hematopathology group without independent review.Of 115 FNA procedures, 93 were completed for the initial evaluation of lymphoma and 22 were done for assessment of relapsed disease. Of the 93 FNA attempts at initial diagnosis, only 27 (29%) were given a specific and complete histologic diagnosis using an accepted classification system (Working Formulation, Revised European-American Classification of Lymphoid Neoplasms, WHO). For the 22 FNAs done for recurrent disease, only nine (41%) were classified using an accepted system. Sixty-seven (72%) of the 93 FNAs performed for the evaluation of initial disease had subsequent excisional biopsies. Among these paired comparisons, only eight (12%) of 67 FNA diagnoses were correlated with the subsequent excisional biopsy diagnosis. Immunophenotyping was completed on 24 of the 67 paired FNAs. Seven of the 24 FNAs with immunophenotyping (29%) were correlated with subsequent histology on excisional biopsy. Only one (2%) of 43 FNA diagnoses, based on morphology alone, was correlated with subsequent excisional biopsy diagnosis.Overall, FNA for lymphoma diagnosis is not helpful, not cost effective, and in addition may misguide treatment.