tbuckley/cabot-search huggingface dataset:
Differential ability of isolated H-2 Kb subsets to serve as TCR ligands for allo-specific CTL clones: potential role for N-linked glycosylation.
Authors: L Shen, K P Kane
Journal: The Journal of Experimental Medicine (1995)

It is not known whether all forms of cell surface peptide-class I complexes, when bound with relevant peptide antigen, are recognized by T cells. We demonstrate herein that two distinct subsets of the murine H-2 Kb molecule can be separately isolated from H-2b-expressing cell lines using Y3 mAb immunoaffinity chromatography. Although both isolated Kb subsets were found to be strongly reactive with Y3 mAb by ELISA, one Kb subset is S19.8 mAb reactive (Ly-m11+Kb subset) and exhibits low reactivity with the M1/42 antibody, while the other subset is negative for the Ly-m11 epitope and highly reactive with the M1/42 antibody (M1/42high Kb subset). More importantly, whereas the M1/42high Kb subset is a very effective ligand for both TCR and CD8, the Ly-m11+ Kb subset could only function as a CD8 ligand, as determined in allo-specific CD8+ CTL clone adhesion and degranulation assays. Peptides acid-eluted from both Kb subsets sensitized Kb-transfected T2 cells expressing "peptide empty" Kb for lysis to a similar extent by allo-CTL clones, indicating that relevant endogenous peptide antigens are not limiting in the Ly-m11+ Kb subset. The major distinction identified between the two Kb subsets is that they differ substantially in their degree of N-linked glycosylation, with the Ly-m11+ subset containing Kb molecules with larger and more complex carbohydrate modifications than the M1/42high subset. The differences in glycosylation may explain the functional differences observed between the two Kb subsets. It is therefore possible that some forms of glycosylation on class I molecules interfere with TCR recognition and may limit CD8+ T cell responses, perhaps under circumstances where peptide antigen is limiting.
Why do cancer drugs get such an easy ride?
Authors: D. W. Light, J. Lexchin
Journal: BMJ (2015)

Diaphragm has a main function in core stabilization which can be defined as the capability of stabilizing the position and movement of the trunk over the pelvis. Diaphragmatic control may facilitate inspiration and decrease the work of breathing and dyspnea. The aim of this study is to compare the immediate effect of basic deep breathing exercise and core stabilization exercise. The study included 32 students (7M,25F; 21.46±0.71 years) without any chronic respiratory diseases. Pulmonary functions of participants were evaluated by spirometry. We evaluated the thoracic mobility by using basic tape measurement from axilla, epigastric and subcostal regions. The volunteers were randomly divided into a core stabilization exercise group (SG) (n=21) and a control group (CG) (n=11). The biofeedback unit (SPB) was placed under the lumbar 5th vertebra and patients attempted to maintain their core stability performing neutral zones in SG. Furthermore, physiotherapist tried to improve thoracolumbar awareness by following changes from SPB and volunteers assured a constant lumbar position during basic deep breathing exercise for 20 minutes. The CG was performed basic deep breathing exercises in a back supported sitting position for 20 minutes. Both groups completed the exercises for once and we aimed to observe the immediate differences between groups. The main results of this study comparing two groups, SG showed greater improvements in thoracic mobility from axilla, epigastric and subcostal regions (p&lt;0.01). In conclusion, adding core stabilization exercises to basic deep breathing exercise may be more effective due to the improvements in thoracic mobility.
Dark lumen magnetic resonance colonography: comparison with conventional colonoscopy for the detection of colorectal pathology
Authors: W Ajaj
Journal: Gut (2003)

The purpose of this study was to assess the feasibility and usefulness of a new magnetic resonance (MR) colonography technique for the detection of colorectal pathology in comparison with conventional colonoscopy as the standard of reference.A total of 122 subjects with suspected colorectal disease underwent "dark lumen" MR colonography. A contrast enhanced T1w three dimensional VIBE sequence was collected after rectal administration of water. The presence of colorectal masses and inflammatory lesions were documented. Results were compared with those of a subsequently performed colonoscopy.MR colonography was found to be accurate regarding detection of clinically relevant colonic lesions exceeding 5 mm in size, with sensitivity and specificity values of 93%/100%.Dark lumen MR colonography can be considered as a promising alternative method for the detection of colorectal disease. In addition, it allows assessment of extraluminal organs.
Phase II trial of cisplatin and gemcitabine in advanced squamous-cell carcinoma of the head and neck
Authors: R. Hitt, D. Castellano, M. Hidalgo, R. García-Carbonero, M. Peña, A. Brandariz, J.M. Millán, J.J. Alvarez Vincent, H. Cortés-Funes
Journal: Annals of Oncology (1998)
Discrimination of Nonobstructive Hypertrophic Cardiomyopathy From Hypertensive Left Ventricular Hypertrophy on the Basis of Strain Rate Imaging by Tissue Doppler Ultrasonography
Authors: Tomoko S. Kato, Akiko Noda, Hideo Izawa, Akira Yamada, Koji Obata, Kohzo Nagata, Mitsunori Iwase, Toyoaki Murohara, Mitsuhiro Yokota
Journal: Circulation (2004)

The differentiation of hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) on the basis of morphological information obtained by conventional echocardiography is occasionally problematic. We investigated whether strain rate (SR) imaging derived from tissue Doppler imaging (TDI) is able to discriminate HCM from H-LVH.Conventional echocardiography and TDI were performed with 34 patients with LVH and 16 reference subjects. Mean values of systolic strain (epsilon(sys)), peak systolic SR, and early diastolic SR obtained from 8 left ventricular (LV) segments were calculated. LV pressures were recorded simultaneously in the patients. Patients were diagnosed with HCM (n=20) or H-LVH (n=14) on the basis of conventional echocardiography and endomyocardial biopsy findings. Multivariate analysis revealed that septum/posterior wall thickness ratio (P=0.00013) and epsilon(sys) (P<0.0001) were each able to discriminate HCM from H-LVH. A epsilon(sys) cutoff value of -10.6% discriminated between HCM and H-LVH with a sensitivity of 85.0%, specificity of 100.0%, and predictive accuracy of 91.2%. The combination of the septum/posterior wall thickness ratio and epsilon(sys) discriminated HCM from H-LVH with a predictive accuracy of 96.1%. The epsilon(sys) parameter was significantly correlated with pulmonary arterial wedge pressure, LV end-diastolic pressure, the peak positive first derivative of LV pressure, and the time constant of LV pressure decay.SR imaging is able to discriminate HCM from H-LVH, with epsilon(sys) reflecting myocardial contractile and lusitropic properties.
Dose-finding study of weekly 24-h continuous infusion of 5-fluorouracil associated with alternating oxaliplatin or irinotecan in advanced colorectal cancer patients
Authors: L. Cals, O. Rixe, E. François, R. Favre, L. Merad, G. Deplanque, A. Laadem, P. Juin, J.M. Bereder, D. Bernardini, P. Herait
Journal: Annals of Oncology (2004)
Induction of Cancer Cell Death by Self-assembling Nanostructures Incorporating a Cytotoxic Peptide
Authors: Stephany M. Standley, Daniel J. Toft, Hao Cheng, Stephen Soukasene, Jing Chen, Srikumar M. Raja, Vimla Band, Hamid Band, Vincent L. Cryns, Samuel I. Stupp
Journal: Cancer Research (2010)

Nanotechnology offers novel delivery vehicles for cancer therapeutics. Potential advantages of nanoscale platforms include improved pharmacokinetics, encapsulation of cytotoxic agents, enhanced accumulation of therapeutics in the tumor microenvironment, and improved therapeutic structures and bioactivity. Here, we report the design of a novel amphiphilic molecule that self-assembles into nanostructures for intracellular delivery of cytotoxic peptides. Specifically, a cationic alpha-helical (KLAKLAK)(2) peptide that is known to induce cancer cell death by membrane disruption was integrated into a peptide amphiphile (PA) that self-assembles into bioactive, cylindrical nanofibers. PAs are composed of a hydrophobic alkyl tail, a beta-sheet forming peptide, and a bioactive peptide that is displayed on the surface of the nanofiber after self-assembly. PA nanostructures that included (KLAKLAK)(2) were readily internalized by breast cancer cells, in contrast to the (KLAKLAK)(2) peptide that on its own was not cell permeable. (KLAKLAK)(2) nanostructures, but not the peptides alone, also induced breast cancer cell death by caspase-independent and Bax/Bak-independent mechanisms associated with membrane disruption. Significantly, (KLAKLAK)(2) nanostructures induced cell death more robustly in transformed breast epithelial cells than in untransformed cells, suggesting a degree of tumor selectivity. Our results provide proof-of-principle that self-assembling PAs can be rationally designed to generate nanostructures that can efficiently deliver cytotoxic peptides to cancer cells.
Hair Loss in Women
Authors: Jerry Shapiro
Journal: New England Journal of Medicine (2007)

A 45-year-old white woman presents with a 1-year history of scalp-hair loss. She was hospitalized with appendicitis 14 months ago. She has been a vegetarian for 20 years. She takes no medications. Her father was bald. On physical examination, she has diffuse, nonscarring hair thinning with a widened part over the central portion of the scalp. How should this problem be evaluated and treated?
Skeletal muscle weakness in patients with sarcoidosis and its relationship with exercise intolerance and reduced health status
Authors: M A Spruit
Journal: Thorax (2004)

Porcine dendritic cells (DCs) are relatively well characterized, but a clear-cut identification of all DC subsets combined with full transcriptional profiling was lacking, preventing an unbiased insight into the functional specializations of DC subsets. Using a large panel of Abs in multicolor flow cytometry, cell sorting, and RNA sequencing we identified and characterized the porcine equivalent of conventional DCs (cDC) 1 and cDC2 as well as plasmacytoid DCs (pDCs) in the peripheral blood of pigs. We demonstrate that cDC1 are CD135<sup>+</sup>CD14<sup>−</sup>CD172a<sup>low</sup>CADM1<sup>+</sup>wCD11R1<sup>+</sup> cells, cDC2 are CD135<sup>+</sup>CD14<sup>−</sup>CD172a<sup>+</sup>CADM1<sup>+</sup>CD115<sup>+</sup>wCD11R1<sup>+</sup>CD1<sup>+</sup> cells and pDCs are CD4<sup>+</sup>CD135<sup>+</sup>CD172a<sup>+</sup>CD123<sup>+</sup>CD303<sup>+</sup> cells. As described in other species, only cDC1 express <i>BATF3</i> and <i>XCR1</i>, cDC2 express <i>FCER1A</i> and <i>FCGR2B</i>, and only pDCs express <i>TCF4</i> and <i>NRP1</i>. Nevertheless, despite these cross-species conserved subset-specific transcripts, porcine pDCs differed from the species described so far in many expressed genes and transcriptomic profiling clustered pDCs more distantly from cDCs than monocytes. The response of porcine DC subsets to TLR ligands revealed that pDCs are by far the most important source of TNF-α, IL-12p40, and of course IFN-α, whereas cDCs are most efficient in MHC and costimulatory molecule expression. Nevertheless, upregulation of CD40 and CD86 in cDCs was critically influenced or even dependent on the presence of pDCs, particularly for TLR 7 and 9 ligands. Our data demonstrate that extrapolation of data on DC biology from one species to another has to be done with care, and it shows how functional details have evolved differentially in different species.
Insulin-Resistant Diabetes after Total Pancreatectomy
Authors: Bessie Dituri
Journal: New England Journal of Medicine (1954)

CONTRARY to speculation diabetes mellitus that follows total pancreatectomy in man is relatively mild. In the absence of infection or other complications the requirement for insulin is usually stable and ranges from 20 to 40 units daily. There is relatively little tendency to spontaneous ketosis and coma, but insulin sensitivity has been a frequent problem in management. The marked contrast of these findings with those in many cases of naturally occurring diabetes mellitus has stimulated consideration of factors besides lack of insulin that produce hyperglycemia and ketosis and require large doses of insulin for correction.In the following case, which . . .
Differential Expression of MicroRNAs in CD34+ Cells of 5q- Syndrome
Authors: Hana Votavova, Martina Grmanova, Michaela Dostalova Merkerova, Monika Belickova, Alzbeta Vasikova, Radana Neuwirtova, Jaroslav Cermak
Journal: Journal of Hematology & Oncology (2011)

Myelodysplastic syndrome with isolated chromosome 5q deletion (5q- syndrome) is a clonal stem cell disorder characterized by ineffective hematopoiesis. MicroRNAs (miRNAs) are important regulators of hematopoiesis and their aberrant expression was detected in some clonal hematopoietic disorders. We thus analyzed miRNA expressions in bone marrow CD34+ cells of 5q- syndrome patients. Further, we studied gene expressions of miR-143, miR-145, miR-378 and miR-146a mapped within the 5q deletion.Using microarrays we identified 21 differently expressed miRNAs in 5q- patients compared to controls. Especially, miR-34a was markedly overexpressed in 5q- patients, suggesting its role in an increased apoptosis of bone marrow progenitors. Out of four miRNAs at del(5q), only miR-378 and miR-146a showed reduced gene expression in the patients. An integrative analysis of mRNA profiles and predicted putative targets defined potential downstream targets of the deregulated miRNAs. The list of targets included several genes that play an important role in the regulation of hematopoiesis (e.g. KLF4, LEF1, SPI1).The study demonstrates global overexpression of miRNAs is associated with 5q- phenotype. Identification of hematopoiesis-relevant target genes indicates that the deregulated miRNAs may be involved in the pathogenesis of 5q- syndrome by a modulation of these targets. The expression data on miRNAs at del(5q) suggest the presence of mechanisms for compensation of a gene dosage.
Pemphigus vulgaris and pemphigus foliaceus coexisting with oral lichen planus
Authors: B. NEUMANN-JENSEN, N. WORSAAE, E. DABELSTEEN, S. ULLMAN
Journal: British Journal of Dermatology (1980)

Two women, aged 72 and 61 years, had mucocutaneous manifestations of pemphigus vulgaris, and one 76-year-old man had pemphigus foliaceus coexisting with oral lichen planus. Clinical and histopathological findings as well as direct and indirect immunofluorescence studies established the diagnosis.
Role of [<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography Scan in the Follow-Up of Lymphoma
Authors: Pier Luigi Zinzani, Vittorio Stefoni, Monica Tani, Stefano Fanti, Gerardo Musuraca, Paolo Castellucci, Enrica Marchi, Mariapaola Fina, Valentina Ambrosini, Cinzia Pellegrini, Lapo Alinari, Enrico Derenzini, Giancarlo Montini, Alessandro Broccoli, Francesco Bacci, Stefano Pileri, Michele Baccarani
Journal: Journal of Clinical Oncology (2009)

Purpose In lymphoma, [ 18 F]fluorodeoxyglucose positron emission tomography (FDG-PET) is routinely used for initial staging, early evaluation of treatment response, and identification of disease relapse. However, there are no prospective studies investigating the value of serial FDG-PET over time in patients in complete remission. Patients and Methods All patients with lymphoma who achieved the first complete remission were prospectively enrolled onto the study and scheduled for serial FDG-PET scans at 6, 12, 18, and 24 months; further scans were then carried out on an annual basis. Overall, the population included 421 patients (160 patients with Hodgkin's lymphoma [HL], 183 patients with aggressive non-Hodgkin's lymphoma [NHL], and 78 patients with indolent follicular NHL). All patients had a regular follow-up evaluation, including complete clinical and laboratory evaluation, and final assessment of any suspect FDG-PET findings using other imaging procedures (computed tomography [CT] scan) and/or biopsy and/or clinical evolution. FDG-PET findings were reported as positive for relapse, inconclusive (when equivocal), or negative for relapse. Results PET enabled documentation of lymphoma relapse in 41 cases at 6 months, in 30 cases at 12 months, in 26 cases at 18 months, in 10 cases at 24 months, and in 11 cases at more than 36 months. All 36 patients with inconclusive positive PET underwent biopsy; only 12 (33%) of 36 patients had a concomitant suggestion of positivity on CT. A lymphoma relapse was diagnosed in 24 (66%) of 36 patients. Conclusion Our results confirm FDG-PET as a valid tool for follow-up of patients with HL and NHL. In patients with inconclusive positive results, histologic confirmation plays an important role in identifying true relapse.
Implications of Nocturnal Hypertension in Children and Adolescents With Type 1 Diabetes
Authors: Sun Hee Lee, Jae Hyun Kim, Min Jae Kang, Young Ah Lee, Sei Won Yang, Choong Ho Shin
Journal: Diabetes Care (2011)

Diabetes is associated with atherogenic risk factors. Hypertension has a major influence on cardiovascular disease in diabetic patients. Ambulatory blood pressure monitoring (ABPM) is useful for identifying nocturnal hypertension. Carotid intima-media thickness (cIMT) is a good measure for identifying subclinical atherosclerosis. This study aimed to evaluate whether nocturnal hypertension affects atherosclerosis in children and adolescents with type 1 diabetes and to investigate the relationship between atherogenic risk factors and cIMT.ABPM and cIMT were measured in 82 diabetic children and adolescents. We reviewed the hemoglobin A(1c) levels, 24-h urine microalbumin excretion, lipid profiles, and duration of diabetes. Nocturnal hypertension was defined as hypertension observed only at night.Forty-three (52%) subjects were hypertensive, and 30 subjects were classified as having nocturnal hypertension. cIMT was higher in the nocturnal hypertensive group than in the normotensive group (0.44 ± 0.03 vs. 0.42 ± 0.04 mm, P = 0.026). Among children and adolescents with nonhypertensive blood pressure levels in clinic blood pressure monitoring, cIMT and daytime blood pressure were higher in the nocturnal hypertensive group. All ABPM parameters were significantly related to cIMT in multiple linear regression analysis.This study showed significantly increased cIMT and daytime blood pressure in diabetic children and adolescents with nocturnal hypertension. ABPM may be a useful method for detecting the macrovascular complications of type 1 diabetes. Longitudinal studies are needed to find the causes of nocturnal hypertension and to evaluate the effect of nocturnal hypertension on atherosclerosis in type 1 diabetes.
Gastrointestinal peptides in serum and synovial fluid from patients with inflammatory joint disease.
Authors: I Lygren, M Ostensen, P G Burhol, G Husby
Journal: Annals of the Rheumatic Diseases (1986)

The concentrations of immunoreactive vasoactive intestinal polypeptide (ir-VIP), immunoreactive pancreatic polypeptide (ir-PP), ir-somatostatin, and ir-secretin were measured in serum and synovial fluid from patients suffering from various inflammatory joint diseases. One group of patients were not taking any medication, while another group received anti-inflammatory treatment at the time of sampling. High levels of ir-VIP in the synovial fluid were observed in the untreated group of patients, and the concentration of ir-VIP in the synovial fluid was significantly higher than in parallel serum samples. On the other hand, no significant differences in the concentrations of the other peptides were observed either between serum and synovial fluid or between the two groups of patients. It is suggested that VIP is released locally at the inflammatory site and that VIP may be of significance in inflammatory disorders.
Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer
Authors: Marika Ciprotti, Niall C. Tebbutt, Fook-Thean Lee, Sze-Ting Lee, Hui K. Gan, David C. McKee, Graeme J. O'Keefe, Sylvia J. Gong, Geoffrey Chong, Wendie Hopkins, Bridget Chappell, Fiona E. Scott, Martin W. Brechbiel, Archie N. Tse, Mendel Jansen, Manabu Matsumura, Masakatsu Kotsuma, Rira Watanabe, Ralph Venhaus, Robert A. Beckman, Jonathan Greenberg, Andrew M. Scott
Journal: Journal of Clinical Oncology (2015)

CS-1008 (tigatuzumab) is a humanized, monoclonal immunoglobulin G1 (IgG1) agonistic antibody to human death receptor 5. The purpose of this study was to investigate the impact of CS-1008 dose on the biodistribution, quantitative tumor uptake, and antitumor response in patients with metastatic colorectal cancer (mCRC).Patients with mCRC who had received at least one course of chemotherapy were assigned to one of five dosage cohorts and infused with a weekly dose of CS-1008. Day 1 and day 36 doses were trace-labeled with indium-111 ((111)In), followed by whole-body planar and regional single-photon emission computed tomography (SPECT) imaging at several time points over the course of 10 days.Nineteen patients were enrolled. (111)In-CS-1008 uptake in tumor was observed in only 12 patients (63%). (111)In-CS-1008 uptake and pharmacokinetics were not affected by dose or repeated drug administration. (111)In-CS-1008 biodistribution showed gradual blood-pool clearance and no abnormal uptake in normal tissue. No anti-CS-1008 antibody development was detected. One patient achieved partial response (3.7 months duration), eight patients had stable disease, and 10 patients had progressive disease. Clinical benefit rate (stable disease + partial response) in patients with (111)In-CS-1008 uptake in tumor was 58% versus 28% in patients with no uptake. An analysis of individual lesions showed that lesions with antibody uptake were one third as likely to progress as those without antibody uptake (P = .07). Death-receptor-5 expression in archived tumor samples did not correlate with (111)In-CS-1008 uptake (P = .5) or tumor response (P = .6).Death-receptor-5 imaging with (111)In-CS-1008 reveals interpatient and intrapatient heterogeneity of uptake in tumor, is not dose dependent, and is predictive of clinical benefit in the treatment of patients who have mCRC.