tbuckley/cabot-search huggingface dataset:
Mapping immune processes in intact tissues at cellular resolution
Authors: Christian Brede, Mike Friedrich, Ana-Laura Jordán-Garrote, Simone S. Riedel, Carina A. Bäuerlein, Katrin G. Heinze, Tobias Bopp, Stephan Schulz, Anja Mottok, Carolin Kiesel, Katharina Mattenheimer, Miriam Ritz, Viktoria von Krosigk, Andreas Rosenwald, Hermann Einsele, Robert S. Negrin, Gregory S. Harms, Andreas Beilhack
Journal: Journal of Clinical Investigation (2012)

Understanding the spatiotemporal changes of cellular and molecular events within an organism is crucial to elucidate the complex immune processes involved in infections, autoimmune disorders, transplantation, and neoplastic transformation and metastasis. Here we introduce a novel multicolor light sheet fluorescence microscopy (LSFM) approach for deciphering immune processes in large tissue specimens on a single-cell level in 3 dimensions. We combined and optimized antibody penetration, tissue clearing, and triple-color illumination to create a method for analyzing intact mouse and human tissues. This approach allowed us to successfully quantify changes in expression patterns of mucosal vascular addressin cell adhesion molecule–1 (MAdCAM-1) and T cell responses in Peyer's patches following stimulation of the immune system. In addition, we employed LSFM to map individual T cell subsets after hematopoietic cell transplantation and detected rare cellular events. Thus, we present a versatile imaging technology that should be highly beneficial in biomedical research.
Low-energy helium-neon laser induces melanocyte proliferation via interaction with type IV collagen: visible light as a therapeutic option for vitiligo
Authors: C-C.E. Lan, C-S. Wu, M-H. Chiou, T-Y. Chiang, H-S. Yu
Journal: British Journal of Dermatology (2009)

Background The treatment of vitiligo remains a challenge for clinical dermatologists. We have previously shown that the helium–neon laser (He–Ne laser, 632·8 nm) is a therapeutic option for treatment of this depigmentary disorder. Objectives Addressing the intricate interactions between melanocytes, the most important cellular component in the repigmentation scheme of vitiligo, and their innate extracellular matrix collagen type IV, the current study aimed to elucidate the effects of the He–Ne laser on melanocytes. Methods Cultured melanocytes were irradiated with the He–Ne laser. Relevant biological parameters including cell attachment, locomotion and growth were evaluated. In addition, the potentially involved molecular pathways were also determined. Results Our results show that in addition to suppressing mobility but increasing attachment to type IV collagen, the He–Ne laser stimulates melanocyte proliferation through enhanced α2β1 integrin expression. The expression of phosphorylated cyclic‐AMP response element binding protein (CREB), an important regulator of melanocyte growth, was also upregulated by He–Ne laser treatment. Using a specific mitochondrial uncoupling agent [carbonyl cyanide m‐chlorophenyl‐hydrazone (CCCP)], the proliferative effect of the He–Ne laser on melanocytes was abolished and suppression of melanocyte growth was noted. Conclusions In summary, we have demonstrated that the He–Ne laser imparts a growth stimulatory effect on functional melanocytes via mitochondria‐related pathways and proposed that other minor pathways including DNA damage may also be inflicted by laser treatment on irradiated cells. More importantly, we have completed the repigmentation scheme of vitiligo brought about by He–Ne laser light in vitro and provided a solid theoretical basis regarding how the He–Ne laser induces recovery of vitiligo in vivo.
Met Proto-Oncogene and Insulin-Like Growth Factor Binding Protein 3 Overexpression Correlates with Metastatic Ability in Well-Differentiated Pancreatic Endocrine Neoplasms
Authors: Donna E. Hansel, Ayman Rahman, Michael House, Raheela Ashfaq, Karin Berg, Charles J. Yeo, Anirban Maitra
Journal: Clinical Cancer Research (2004)

Pancreatic endocrine neoplasms are neoplastic proliferations of islet cells or islet cell precursors and are capable of secreting a variety of synthetic products, including insulin, glucagon, gastrin, and vasoactive intestinal peptide. The biological behavior of pancreatic endocrine neoplasms is often unpredictable, and there are few reliable histopathologic criteria reliably correlating with metastatic ability. We have used the Affymetrix U133 GeneChip set (HG_U133 A and B; Affymetrix; Santa Clara, CA) representing approximately 33,000 characterized transcripts to examine global gene expression profiles from well-differentiated nonmetastatic (n=5) and metastatic (n=7) pancreatic endocrine neoplasms to determine molecular markers that predict disease progression. Microarray hybridization data were normalized using the GeneLogic GeneExpress Software System to identify differentially up- and down-regulated genes in metastatic versus nonmetastatic pancreatic endocrine neoplasms. Using a 3-fold change in gene expression as a threshold, we have identified 65 overexpressed and 57 underexpressed genes in metastatic pancreatic endocrine neoplasms as compared with nonmetastatic pancreatic endocrine neoplasms. Several classes of genes, including growth factors and growth factor-related molecules (IGFBP1, IGFBP3, and MET), developmental factors (TBX3 and MEIS2), cytoskeletal factors (beta 1 tubulin and ACTN2), cholesterol homeostasis mediators (LRP5, SLC27A2, and RXRG), intracellular signaling pathway mediators (DYRK1A, PKIB, and AK2), methyltransferases (MGMT and GAMT), and DNA repair and regulatory molecules (CHEK1 and ZNF198), were identified as differentially over- or underexpressed via this method. Immunohistochemical validation of microarray data were performed for two overexpressed genes, namely, the met proto-oncogene (MET) and insulin-like growth factor binding protein 3 (IGFBP3) with tissue microarrays of nonmetastatic (n=24) and metastatic (n=15) pancreatic endocrine neoplasms. Increased expression of IGFBP3 was confirmed in metastatic versus nonmetastatic pancreatic endocrine neoplasms (12 of 15, 80% versus 10 of 24, 42%), as well as in lymph node (6 of 7, 86%) and liver (9 of 9, 100%) metastases. Similarly, overexpression of MET was confirmed in metastatic versus nonmetastatic pancreatic endocrine neoplasms (5 of 15, 33% versus 4 of 24, 17%), as well as in lymph node metastases (4 of 7, 57%) and liver metastases (5 of 9, 56%). The majority of genes that demonstrated altered expression has not been previously identified as differentially expressed in metastatic pancreatic endocrine neoplasm lesions and may therefore represent newly identified molecules in the progression of these lesions.
TRAVEL NOTES.IX. A WINTER SEMESTER.
Authors: LEWELLYS F. BARKER
Journal: JAMA (1904)

Munich, July 21, 1904. Following Gerhardt's example, the autopsy material from cases that have been studied previously in the clinic is thoroughly presented and discussed by Müller. In his epicrisis he is less anxious to confirm a diagnosis which has been made than to emphasize diseased conditions which have been over looked or mistakenly diagnosticated. The origin of a mistake is made clear, and the way it is to be avoided another time pointed out; the saying so frequently on the lips of Gerhardt, "<i>Wir hätten genauer untersuchen sollen,</i>" is evidently impressed on the students. The more advanced students and physicians who attend Milller's clinics are never turned empty away. Notwithstanding his practice of presenting the more important clinical types so that the beginning students may possess standards in the memory and possess them thoroughly, the individual in each case is brought out and the more experienced student, there fore,
Complete endosonographic staging of lung cancer
Authors: Jouke T Annema
Journal: Thorax (2014)

With great interest, I read the article by Kang and colleagues in which they performed a randomised comparison between EBUS-centred versus EUS-centred mediastinal nodal staging of lung cancer.1 As expected, no difference in diagnostic values between the two groups was found. A minimal diagnostic gain of the addition of EUS to EBUS was reported in contrast to a significant diagnostic benefit of the addition of EBUS to EUS. Strikingly, there was a high false-negative rate of EUS regarding the subcarinal station 7—a …
Randomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly people
Authors: Åke Örtqvist, Jonas Hedlund, Lars-Åke Burman, Elisabet Elbel, Margareta Höfer, Maija Leinonen, Ingrid Lindblad, Bo Sundelöf, Mats Kalin
Journal: The Lancet (1998)
Maternal Smoking During Pregnancy and Offspring Conduct Problems
Authors: Darya Gaysina, David M. Fergusson, Leslie D. Leve, John Horwood, David Reiss, Daniel S. Shaw, Kit K. Elam, Misaki N. Natsuaki, Jenae M. Neiderhiser, Gordon T. Harold
Journal: JAMA Psychiatry (2013)

Several studies report an association between maternal smoking during pregnancy and offspring conduct disorder. However, past research evidences difficulty in disaggregating prenatal environmental influences from genetic and postnatal environmental influences.
The circulatory influences of vagal afferents at rest and during coronary occlusion in conscious dogs.
Authors: V S Bishop, D F Peterson
Journal: Circulation Research (1978)

We studied the role of cardiopulmonary vagal afferents in the cardiovascular responses to coronary artery occlusion in conscious dogs with intact carotid sinuses and following functional denervation of the arterial baroreceptors. The contributions of vagal afferents were determined by cold blocking the vagi. In dogs with intact carotid sinuses, coronary artery occlusion produced small decreases in mean cardiac output and arterial pressure, whereas heart rate increased by 35 beats/min. In dogs with intact carotid sinuses, vagal cold block increased mean arterial pressure by 22 +/- 2 (mean +/- SE) mm Hg and heart rate by 90 +/- 6 beats/min. Mean cardiac output increased by 505 +/- 90 ml/min. With the exception of heart rate, responses to coronary occlusion during vagal cold block were similar to the occlusion response prior to vagal cold block. Furthermore, prior occlusion of the coronary artery did not significantly influence the responses to vagal cold block. After arterial baroreceptor denervation, coronary artery occlusion resulted in a substantially greater fall in systemic arterial pressure (-52 mm Hg as compared to -8 mm Hg, with intact carotid sinuses) and peripheral resistance decreased by -0.49 peripheral resistance units (PRU). Vagal cold block following denervation increased the arterial pressure by 49 +/- 10 mm Hg and peripheral resistance by 0.59 +/- 0.13 PRU. Both values were significantly greater than those observed during vagal cold block prior to denervation. In arterial baroreceptor-denervated dogs, vagal blockade significantly attenuated the response to coronary occlusion. Therefore, in conscious dogs, vagal afferents from cardiopulmonary receptors exert a significant inhibitory influence on the peripheral vascular tone. When the carotid sinuses are intact, this inhibitory influence appears to be marked during myocardial ischemia. In the absence of functional arterial baroreflexes, vagal afferent activity contributes to the depressor responses observed during ischemia.
Population-Based Study of Peritumoral Lymphovascular Invasion and Outcome Among Patients With Operable Breast Cancer
Authors: Bent Ejlertsen, Maj-Britt Jensen, Fritz Rank, Birgitte B. Rasmussen, Peer Christiansen, Niels Kroman, Marianne E. Kvistgaard, Marie Overgaard, Dorte B. Toftdahl, Henning T. Mouridsen
Journal: JNCI Journal of the National Cancer Institute (2009)

Lymphovascular invasion has been associated with poor prognosis in women with breast cancer, but it is unclear whether the presence of lymphovascular invasion should be considered sufficient to reclassify breast cancer patients who are at a low risk of recurrence into a high-risk category.Of the 16,172 patients with operable breast cancer who were entered into the Danish Breast Cancer Cooperative Group Registry from January 1, 1996, to December 31, 2002, lymphovascular invasion was classified at primary diagnosis in 16,121 patients as present (n = 2453, 15%) or as absent (n = 13,206, 82%). Patients with at least one of the risk criteria (positive lymph nodes, tumor size > 2 cm, high grade, hormone receptor-negative tumor, or younger than 35 years) were assigned to the high-risk group; the other patients were assigned to the low-risk group. All procedures, including report forms, central review, and querying, were specified in advance. Kaplan-Meier analyses were used to estimate disease-free intervals and overall survival rates among patients with and without lymphovascular invasion, and multivariable analysis was used to adjust for differences in baseline characteristics and therapy. All statistical tests were two-sided.Complete follow-up was achieved for 15,659 patients. The median estimated potential follow-up was 6.4 years for invasive disease-free interval and 7.7 years for overall survival. Invasive disease-free interval and overall survival were statistically significantly associated with lymphovascular invasion within the high-risk group (hazard ratio [HR] for invasive disease = 2.29, 95% confidence interval [CI] = 2.14 to 2.45, P < .001; and HR for death = 2.42, 95% CI = 2.25 to 2.61, P < .001) but not within the low-risk group. At 5 years after surgery, 65.4% (95% CI = 63.5% to 67.3%) and 85.2% (95% CI = 84.5% to 85.9%) of those in the high-risk group with and without lymphovascular invasion were alive; 98.1% (95% CI = 87.6% to 99.7%) and 94.1% (95% CI = 93.2% to 94.8%) of those in the low-risk group with and without lymphovascular invasion were alive. These differences persisted in a multivariable analysis, and for overall survival, a statistically significant interaction (P = .03) was observed between lymphovascular invasion and risk group.In this prospective population-based study, lymphovascular invasion was not an independent high-risk criterion. Lymphovascular invasion should not by itself be considered sufficient to move patients from a low-risk group to a high-risk group.
Streptococcus pneumoniae triggers progression of pulmonary fibrosis through pneumolysin
Authors: S. Knippenberg, B. Ueberberg, R. Maus, J. Bohling, N. Ding, M. Tort Tarres, H.-G. Hoymann, D. Jonigk, N. Izykowski, J. C. Paton, A. D. Ogunniyi, S. Lindig, M. Bauer, T. Welte, W. Seeger, A. Guenther, T. H. Sisson, J. Gauldie, M. Kolb, U. A. Maus
Journal: Thorax (2015)

<h3>Rationale</h3> Respiratory tract infections are common in patients suffering from pulmonary fibrosis. The interplay between bacterial infection and fibrosis is characterised poorly. <h3>Objectives</h3> To assess the effect of Gram-positive bacterial infection on fibrosis exacerbation in mice. <h3>Methods</h3> Fibrosis progression in response to <i>Streptococcus pneumoniae</i> was examined in two different mouse models of pulmonary fibrosis. <h3>Measurements and main results</h3> We demonstrate that wild-type mice exposed to adenoviral vector delivery of active transforming growth factor-β1 (TGFß1) or diphteria toxin (DT) treatment of transgenic mice expressing the DT receptor (DTR) under control of the surfactant protein C (SPC) promoter (SPC-DTR) to induce pulmonary fibrosis developed progressive fibrosis following infection with Spn, without exhibiting impaired lung protective immunity against Spn. Antibiotic treatment abolished infection-induced fibrosis progression. The cytotoxin pneumolysin (Ply) of Spn caused this phenomenon in a TLR4-independent manner, as Spn lacking Ply (SpnΔply) failed to trigger progressive fibrogenesis, whereas purified recombinant Ply did. Progressive fibrogenesis was also observed in AdTGFβ1-exposed Ply-challenged TLR4 KO mice. Increased apoptotic cell death of alveolar epithelial cells along with an attenuated intrapulmonary release of antifibrogenic prostaglandin E2 was found to underlie progressive fibrogenesis in Ply-challenged AdTGFβ1-exposed mice. Importantly, vaccination of mice with the non-cytotoxic Ply derivative B (PdB) substantially attenuated Ply-induced progression of lung fibrosis in AdTGFβ1-exposed mice. <h3>Conclusions</h3> Our data unravel a novel mechanism by which infection with Spn through Ply release induces progression of established lung fibrosis, which can be attenuated by protein-based vaccination of mice.
Progression of early features of spinocerebellar ataxia type 2 in individuals at risk: a longitudinal study
Authors: Luis Velázquez-Pérez, Roberto Rodríguez-Labrada, Nalia Canales-Ochoa, Jacqueline Medrano Montero, Gilberto Sánchez-Cruz, Raúl Aguilera-Rodríguez, Luis E Almaguer-Mederos, José M Laffita-Mesa
Journal: The Lancet Neurology (2014)
An Open, Randomized, Parallel-Group Study to Compare the Efficacy and Safety Profile of Inhaled Human Insulin (Exubera) With Glibenclamide as Adjunctive Therapy in Patients With Type 2 Diabetes Poorly Controlled on Metformin
Authors: Anthony H. Barnett, Manfred Dreyer, Peter Lange, Marjana Serdarevic-Pehar
Journal: Diabetes Care (2006)

To compare the efficacy and safety profile of adding inhaled human insulin (INH) (Exubera) or glibenclamide to metformin monotherapy in patients with poorly controlled type 2 diabetes.We conducted an open-label, parallel, 24-week multicenter trial. Patients uncontrolled on metformin were randomized to adjunctive INH (n = 243) or glibenclamide (n = 233). Before randomization, patients were divided into two HbA(1c) (A1C) arms: > or =8 to < or =9.5% (moderately high) and >9.5 to < or =12% (very high). The primary efficacy end point was A1C change from baseline.Mean adjusted A1C changes from baseline were -2.03 and -1.88% in the INH and glibenclamide groups, respectively; between-treatment difference -0.17% (95% CI -0.34 to 0.01; P = 0.058), consistent with the noninferiority criterion. In the A1C >9.5% arm, inhaled insulin demonstrated a significantly greater reduction in A1C than glibenclamide, between-treatment difference -0.37% (-0.62 to -0.12; P = 0.004). In the A1C < or =9.5% arm, between-treatment difference was 0.04% (-0.19 to 0.27; P = 0.733). Hypoglycemia (events per subject-month) was greater with INH (0.18) than glibenclamide (0.08), risk ratio 2.24 (1.58-3.16), but there were no associated discontinuations. Other adverse events, except increased cough in the INH group, were similar. At week 24, changes from baseline in pulmonary function parameters were small. Insulin antibody binding increased more with INH but did not have any associated clinical manifestations.In patients with type 2 diabetes poorly controlled on metformin, adding INH or glibenclamide was similarly effective in improving glycemic control, and both were well tolerated. A predefined subgroup with very high A1C (>9.5%) was more effectively treated with the addition of INH.
Intracrine Cysteinyl Leukotriene Receptor–mediated Signaling of Eosinophil Vesicular Transport–mediated Interleukin-4 Secretion
Authors: Christianne Bandeira-Melo, Lesley J. Woods, Mojabeng Phoofolo, Peter F. Weller
Journal: The Journal of Experimental Medicine (2002)

We investigated whether cysteinyl leukotrienes (cysLT) are intracrine signal transducers that regulate human eosinophil degranulation mechanisms. Interleukin (IL)-16, eotaxin, and RANTES stimulate vesicular transport–mediated release of preformed, granule-derived IL-4 and RANTES from eosinophils and the synthesis at intracellular lipid bodies of LTC4, the dominant 5-lipoxygenase–derived eicosanoid in eosinophils. 5-Lipoxygenase inhibitors blocked IL-16–, eotaxin-, and RANTES-induced IL-4 release; but neither exogenous LTC4, LTD4, nor LTE4 elicited IL-4 release. Only after membrane permeabilization enabled cysLTs to enter eosinophils did LTC4 and LTD4 stimulate IL-4, but not RANTES, release. LTC4-elicited IL-4 release was pertussis toxin inhibitable, but inhibitors of the two known G protein–coupled cysLT receptors (cysLTRs) (CysLT1 and CysLT2) did not block LTC4-elicited IL-4 release. LTC4 was 10-fold more potent than LTD4 and at low concentrations (0.3–3 nM) elicited, and at higher concentrations (&amp;gt;3 nM) inhibited, IL-4 release from permeabilized eosinophils. Likewise with intact eosinophils, LTC4 export inhibitors, which increased intracellular LTC4, inhibited eotaxin-elicited IL-4 release. Thus, LTC4 acts, via an intracellular cysLTR distinct from CysLT1 or CysLT2, as a signal transducer to selectively regulate IL-4 release. These results demonstrate that LTC4, well recognized as a paracrine mediator, may also dynamically govern inflammatory and immune responses as an intracrine mediator of eosinophil cytokine secretion.
Adriamycin and Enhanced Radiation Reaction in Normal Esophagus and Skin
Authors: F. ANTHONY GRECO
Journal: Annals of Internal Medicine (1976)

Clinical evaluation of 10 patients with small cell carcinoma of the lung treated with radiotherapy and periodic cycles of combination chemotherapy with cyclophosphamide, vincristine, and adriamycin showed frequent and occasionally severe esophageal and skin reactions. Eight of the 10 patients had esophagitis, four required supportive intravenous fluids, and two subsequently developed esophageal narrowing and stricture formation. Recurrent esophagitis with augmentation of injury in the recently irradiated esophagus was observed 11 times in eight of the 10 patients after cycles of chemotherapy, and contributed to the sustained toxicity seen in two patients. Dermatitis in the form of moist desquamation was observed in five of the patients at very low doses of supervoltage radiation therapy. Acute pulmonary reactions were notably absent. This combination of chemotherapy, particularly adriamycin, potentiates the effect of radiotherapy on the normal esophagus and skin, and further implicates the radiosensitizing property of adriamycin.
Does Patient Behavior or Access Factors Have the Largest Influence on Screening in Type 1 Diabetes?
Authors: Rashida Dorsey, Thomas Songer, Janice Zgibor, Sheryl Kelsey, Said Ibrahim, Trevor Orchard
Journal: Diabetes Care (2007)

Successful disease management is heavily influenced by access to care issues and patient behavior. Screening tests to detect chronic complications are part of diabetes management and may be influenced by access to care or patient decisions. The objective of this research was to examine how strongly access to care and patient behavior predict screening practices.Information on screening practices, access to care, and diabetes management were identified from the Pittsburgh Epidemiology of Diabetes Complications Study at two time points: 1998-2001 and 2002-2006. Information on access to care and patient behavior identified in 1998-2001 were examined relative to screening practices observed in 2002-2006.Access-to-care issues positively predicted subsequent screening practices. Specifically, specialist care visits, number of doctor visits, and intensive insulin therapy were all strong predictors for screening use. Receipt of the recommended level of screening tests was also positively associated with the patient behavior of daily blood glucose testing.The findings of this study show that access to care, in general, and access to quality diabetes care, in specific, play a key role in the use of recommended screening tests in type 1 diabetic patients. These data suggest that future efforts to improve screening practices in the type 1 diabetic population should address issues related to access to care.