tbuckley/cabot-search huggingface dataset:
Dietary Fat in Breast Cancer Survival
Authors: Nour Makarem, Urmila Chandran, Elisa V. Bandera, Niyati Parekh
Journal: Annual Review of Nutrition (2013)

Laboratory evidence suggests a plausible role for dietary fat in breast cancer pathophysiology. We conducted a systematic literature review to assess the epidemiological evidence on the impact of total dietary fat and fat subtypes, measured pre- and/or postcancer diagnosis, in relation to breast cancer–specific and all-cause mortality among breast cancer survivors. Studies were included if they were in English, had a sample size ≥200, and presented the hazard ratio/rate ratio for recurrence, disease-specific mortality, or all-cause mortality (n = 18). Although the results are mixed, most studies suggested that higher saturated fat intake prediagnosis was associated with increased risk of breast cancer–specific and all-cause mortality. Postdiagnostic trans fat intake was associated with a 45% and 78% increased risk of all-cause mortality. Higher monounsaturated fat intake before and after diagnosis was generally associated with increased risk of all-cause and breast cancer–specific mortality, albeit the majority of the studies were statistically nonsignificant. Two studies evaluating omega-3 fat intake suggested an inverse association with all-cause mortality. Although there were too few studies on fat subtypes to draw definitive conclusions, high consumption of saturated fat may exert a detrimental effect on breast cancer–specific and all-cause mortality, whereas omega-3 fat may be beneficial. The inconsistent and limited evidence warrants research to assess the impact of consumption of fat subtypes on breast cancer recurrence and mortality.
Capillary Deposition of Complement Split Product C4d in Renal Allografts is Associated with Basement Membrane Injury in Peritubular and Glomerular Capillaries
Authors: Heinz Regele, Georg A. Böhmig, Antje Habicht, Daniela Gollowitzer, Martin Schillinger, Susanne Rockenschaub, Bruno Watschinger, Dontscho Kerjaschki, Markus Exner
Journal: Journal of the American Society of Nephrology (2002)

Endothelial deposition of the complement split product C4d is an established marker of antibody-mediated acute renal allograft rejection. A contribution of alloantibody-dependent immune reactions to chronic rejection is under discussion. In this study, the association of immunohistochemically detected endothelial C4d deposition in peritubular capillaries (PTC) with morphologic features of chronic renal allograft injury was investigated in a large study cohort. C4d deposits in PTC were detected in 73 (34%) of 213 late allograft biopsies performed in 213 patients more than 12 mo after transplantation (median, 4.9 yr) because of chronic allograft dysfunction. Endothelial C4d deposition was found to be associated with chronic transplant glomerulopathy (CG) (P < 0.0001), with basement membrane multilayering in PTC (P = 0.01), and with an accumulation of mononuclear inflammatory cells in PTC (P < 0,001). Furthermore, C4d deposits in PTC (in biopsies with normal glomerular morphology) were associated with development of CG in follow-up biopsies. Other morphologic features of chronic allograft nephropathy (with exception of tubular atrophy) were not associated with C4d deposits in PTC. Analyses of previous and follow-up biopsies revealed that C4d deposits may occur de novo and may also disappear at any time after transplantation. In conclusion, the data suggest that complement activation in renal microvasculature, indicating humoral alloreactivity, contributes to chronic rejection characterized by chronic transplant glomerulopathy and basement membrane multilayering in PTC.
Fully Automated Closed-Loop Insulin Delivery Versus Semiautomated Hybrid Control in Pediatric Patients With Type 1 Diabetes Using an Artificial Pancreas
Authors: Stuart A. Weinzimer, Garry M. Steil, Karena L. Swan, Jim Dziura, Natalie Kurtz, William V. Tamborlane
Journal: Diabetes Care (2008)

OBJECTIVE—The most promising β-cell replacement therapy for children with type 1 diabetes is a closed-loop artificial pancreas incorporating continuous glucose sensors and insulin pumps. The Medtronic MiniMed external physiological insulin delivery (ePID) system combines an external pump and sensor with a variable insulin infusion rate algorithm designed to emulate the physiological characteristics of the β-cell. However, delays in insulin absorption associated with the subcutaneous route of delivery inevitably lead to large postprandial glucose excursions. RESEARCH DESIGN AND METHODS—We studied the feasibility of the Medtronic ePID system in youth with type 1 diabetes and hypothesized that small manual premeal “priming” boluses would reduce postprandial excursions during closed-loop control. Seventeen adolescents (aged 15.9 ± 1.6 years; A1C 7.1 ± 0.8%) underwent 34 h of closed-loop control; 8 with full closed-loop (FCL) control and 9 with hybrid closed-loop (HCL) control (premeal priming bolus). RESULTS—Mean glucose levels were 135 ± 45 mg/dl in the HCL group versus 141 ± 55 mg/dl in the FCL group (P = 0.09); daytime glucose levels averaged 149 ± 47 mg/dl in the HCL group versus 159 ± 59 mg/dl in the FCL group (P = 0.03). Peak postprandial glucose levels averaged 194 ± 47 mg/dl in the HCL group versus 226 ± 51 mg/dl in the FCL group (P = 0.04). Nighttime control was similar in both groups (111 ± 27 vs. 112 ± 28 mg/dl). CONCLUSIONS—Closed-loop glucose control using an external sensor and insulin pump provides a means to achieve near-normal glucose concentrations in youth with type 1 diabetes during the overnight period. The addition of small manual priming bolus doses of insulin, given 15 min before meals, improves postprandial glycemic excursions.
Genetic Aspects of Infantile Autism
Authors: S E Folstein
Journal: Annual Review of Medicine (1985)

Infantile autism probably has many etiologies. Several specific genetic disorders appear to be associated with the syndrome much more often than would be expected by chance, but these account for only a minority of cases. In the majority of cases, where etiology is still unknown, genetic factors probably also play a role. Evidence suggests, however, that it is not autism per se that is inherited, but less severe abnormalities of language and cognition, which in turn lead to a predisposition to the development of autism in infants.
Intravenous fosfomycin for the treatment of nosocomial infections caused by carbapenem-resistant Klebsiella pneumoniae in critically ill patients: a prospective evaluation
Authors: A. Michalopoulos, S. Virtzili, P. Rafailidis, G. Chalevelakis, M. Damala, M.E. Falagas
Journal: Clinical Microbiology and Infection (2009)
A STUDY OF 138 ELDERLY FIRST ADMISSIONS
Authors: J. MARTIN MYERS, DANA SHELDON, S. SUE ROBINSON
Journal: American Journal of Psychiatry (1963)

From the data presented, we have drawn the following conclusions: 1. The first hospitalization is very useful for most mental patients over 65 years. The median stay was 42 days. 2. One year post admission, 19% were dead, 48% were home, and 39% were able to care for themselves physically. 3. Total follow-up, ranging from 2 years, 2 months, to 7 years, found 42% dead, 39% at home, 33% able to care for themselves. 4. Physical impairment was related to the admission directly in 50%, indirectly in 11%, and was unrelated in 37%. The medical impairment status on admission correlated with the final outcome in terms of mortality. 5. There is a marked discrepancy in diagnostic categories between patients from this hospital and state hospital systems. Some of this is due to differences in social class, but not all. The percentage of affective reactions is especially striking—45%. 6. The single most important factor in decreased mortality is treatment of the patient as a total psychobiologic unit. The intermingling of elderly patients with the total patient group may be important therapeutically.
Reproducibility of twitch mouth pressure, sniff nasal inspiratory pressure, and maximal inspiratory pressure
Authors: JO Maillard, L Burdet, G van Melle, JW Fitting
Journal: European Respiratory Journal (1998)

Twitch mouth pressure (Pmo,tw) during magnetic phrenic nerve stimulation and sniff nasal inspiratory pressure (SNIP) were recently proposed as alternative noninvasive methods for assessing inspiratory muscle strength. This study aimed to compare their reproducibility with maximal inspiratory pressure (MIP) in normal subjects. Ten healthy subjects were studied at functional residual capacity in semirecumbent position. Cervical magnetic phrenic nerve stimulation was performed during gentle expiration against an occlusion incorporating a small leak. Constancy of stimulation was controlled by recording diaphragmatic electromyogram. Within and between-session reproducibility of pressure were studied for Pmo,tw, SNIP, and MIP. The subjects were studied during a session of 10 manoeuvres repeated after 1 day and 1 month. The mean values were 16 cmH2O for Pmo,tw, 118 cmH2O for SNIP, and 115 cmH2O for MIP. For the three tests, the within subject variation was small in relation to between-subject variation, with the intraclass correlation coefficient ranging 0.79-0.90 for Pmo,tw, 0.85-0.92 for SNIP, and 0.88-0.92 for MIP. At 1 day interval, the coefficient of repeatability (2 SD of differences) was 3.6 cmH2O for Pmo,tw, 32 cmH2O for SNIP and 28 cmH2O for MIP. At 1 month interval, the coefficient of repeatability was 5.8 cmH2O for Pmo,tw, 23 cmH2O for SNIP and 21 cmH2O for MIP. We conclude that the within session reproducibility of the new tests twitch mouth pressure and sniff nasal inspiratory pressure is sufficient to be clinically useful. For sniff nasal inspiratory pressure, the between session reproducibility established after 1 day was maintained after 1 month. For twitch mouth pressure, the between session reproducibility declined slightly after 1 month. These characteristics should be considered when using these methods to follow an individual patient over time.
Normal Lung Function in Subjects Heterozygous for Surfactant Protein-B Deficiency
Authors: ROGER D. YUSEN, ALAN H. COHEN, AARON HAMVAS
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Inherited deficiency of surfactant protein-B (SP-B) is a fatal autosomal recessive disorder of lung cell metabolism caused most frequently by a frameshift mutation in codon 121 of the SP-B gene (121ins2) and is characterized by rapidly progressive respiratory failure immediately after birth. Lungs from genetically engineered heterozygous SP-B–deficient mice exhibit decreased compliance and mild air trapping. To determine whether pulmonary function of heterozygous SP-B–deficient humans is similarly affected, we studied nine heterozygous subjects 16 to 44 yr of age and two unaffected subjects 7 and 23 yr of age from five families of 121ins2 SP-B-deficient infants. An increase in residual volume was noted in one heterozygous family member and one unaffected family member. Compliance, maximal transpulmonary pressure, air flow, and gas exchange were normal in all heterozygous subjects tested. These data suggest that humans heterozygous for the 121ins2 mutation have normal pulmonary function through the first four decades of life. The impact of advancing age and environmental exposures on the lung function of heterozygotes remains to be determined.
IKKε and TBK1 are essential components of the IRF3 signaling pathway
Authors: Katherine A. Fitzgerald, Sarah M. McWhirter, Kerrie L. Faia, Daniel C. Rowe, Eicke Latz, Douglas T. Golenbock, Anthony J. Coyle, Sha-Mei Liao, Tom Maniatis
Journal: Nature Immunology (2003)
Slow calcium waves and redox changes precede mitochondrial permeability transition pore opening in the intact heart during hypoxia and reoxygenation
Authors: Sean M. Davidson, Derek M. Yellon, Michael P. Murphy, Michael R. Duchen
Journal: Cardiovascular Research (2011)

Opening of the mitochondrial permeability transition pore (mPTP) is an important step on the pathway towards cardiomyocyte death, defining the extent of injury following cardiac ischaemia and reperfusion. In isolated mitochondria, mPTP opening is triggered by calcium overload facilitated by oxidative stress. In isolated cells, however, it has been suggested that mPTP opening occurs before calcium overload and is stimulated by oxidative stress. Our objective was to establish the events that cause mPTP opening in the intact heart. We performed multiphoton imaging of Langendorff-perfused mouse hearts expressing an inducible, Ca2+-sensitive reporter (circularly Permuted GFP and calmodulin (CaM), version 2), to examine the spatiotemporal relationship between [Ca2+]c, redox state, and mPTP opening in the intact heart during hypoxia and reoxygenation at sub-myocyte resolution. We found that during reperfusion, calcium waves propagated across multiple cells at 3.3 µm/s. mPTP opening caused an abrupt loss of mitochondrial membrane potential, measured using a potentiometric dye, which was invariably preceded by a rise in [Ca2+]c. The probability that localized [Ca2+]c waves led to mPTP opening was greater early during reoxygenation. During reoxygenation, coordinated redox changes also occurred across large regions and preceded mPTP opening on average by 122 ± 38 s. Fewer [Ca2+] waves led to mPTP opening in the presence of mPTP inhibitor cyclosporin A or mitochondrial-targeted scavenger of reactive oxygen species, MitoQ. These experiments define the spatiotemporal relationship between changes in [Ca2+]c, redox state and mPTP opening during reoxygenation in the intact heart. Tissue oxidation coincident with localized calcium waves together conspire to cause mPTP opening and subsequent cell death.
525 EFFECT OF 5-HT7 RECEPTOR BLOCKADE ON LIVER REGENERATION AFTER PARTIAL HEPATECTOMY
Authors: K.N. Tzirogiannis, G.K. Papadimas, M.D. Demonakou, S.D. Skaltsas, A.D. Grypioti, K.T. Kourentzi, K.N. Alexandropoulou, N. Tairis, M.G. Mykoniatis, G.I. Panoutsopoulos
Journal: Journal of Hepatology (2008)
Splenectomy in patients with AIDS
Authors: Anna Mathew, Mario C. Raviglione, Usha Niranjan, Maria T. Sabatini, Ariel Distenfeld
Journal: American Journal of Hematology (1989)

To establish the indications for splenectomy in patients with human immunodeficiency virus (HIV) infection we retrospectively analyzed 12 patients who underwent splenectomy. Patients with HIV infection who had immune thrombocytopenic purpura (ITP) were excluded as they had no splenomegaly and a definite indication for splenectomy exists in some of these patients. All 12 patients were anemic; 6 were thrombocytopenic and 6 leukopenic. All patients had splenomegaly and all were febrile. At surgery 3 patients were found to have Mycobacterium avium intracellulare (MAI) infection; 2 had splenic abscess due to Salmonella group D; 1 each had cytomegalovirus (CMV) splenitis and localized Kaposi's sarcoma (KS) of the spleen. No definite histopathologic diagnosis could be made in five patients, all of whom had evidence of extramedullary hematopoiesis. The degree of splenic enlargement did not correlate with the outcome. Both clinical and hematologic improvements were achieved in patients with splenic abscess and in patients who had splenomegaly, anemia, and thrombocytopenia. The presence of either of these findings constitutes an indication for splenectomy. Anemia and/or leukopenia without thrombocytopenia failed to improve; the presence of MAI and active CMV infection also resulted in failure. The presence of either of these conditions may be considered a contraindication to splenectomy.
Antigen-Experienced CD4+ T Cells Limit Naïve T-Cell Priming in Response to Therapeutic Vaccination<i>In vivo</i>
Authors: Chris Schiering, Jlenia Guarnerio, Veronica Basso, Luca Muzio, Anna Mondino
Journal: Cancer Research (2010)

CD4(+) T cells play a central role in protective immunity. In a mouse tumor model, we previously found that tumor growth elicits natural CD4(+) T-cell responses, but impedes therapeutic vaccination. We show here that inhibition of vaccine-mediated naïve T-cell priming is due to the presence of a minor but distinct population of tumor-reactive CD4(+) T cells. These cells are generated in the tumor draining lymph nodes (LN), are capable of systemic redistribution, and act to limit the representation of antigen-bearing MHC II(+) antigen-presenting cells (APC) in contralateral LNs or when transferred to tumor-free mice. Surgical tumor resection, which lowers the representation of tumor primed CD4(+) T cells, restored to some extent vaccine-induced CD4(+) T-cell activation. Likewise, vaccination with artificial APCs (latex beads) or higher numbers of dendritic cells allowed comparable CD4(+) T-cell priming in tumor-free and tumor-bearing mice. Together, our results emphasize the ability of antigen-experienced CD4(+) T lymphocytes to interfere with therapeutic vaccination and highlight the need for alternative strategies able to surmount limitations imposed by ongoing immune responses.
Bortezomib-Based Graft-Versus-Host Disease Prophylaxis in HLA-Mismatched Unrelated Donor Transplantation
Authors: John Koreth, Kristen E. Stevenson, Haesook T. Kim, Sean M. McDonough, Bhavjot Bindra, Philippe Armand, Vincent T. Ho, Corey Cutler, Bruce R. Blazar, Joseph H. Antin, Robert J. Soiffer, Jerome Ritz, Edwin P. Alyea
Journal: Journal of Clinical Oncology (2012)

HLA-mismatched unrelated donor (MMUD) hematopoietic stem-cell transplantation (HSCT) is associated with increased graft-versus-host disease (GVHD) and impaired survival. In reduced-intensity conditioning (RIC), neither ex vivo nor in vivo T-cell depletion (eg, antithymocyte globulin) convincingly improved outcomes. The proteasome inhibitor bortezomib has immunomodulatory properties potentially beneficial for control of GVHD in T-cell-replete HLA-mismatched transplantation.We conducted a prospective phase I/II trial of a GVHD prophylaxis regimen of short-course bortezomib, administered once per day on days +1, +4, and +7 after peripheral blood stem-cell infusion plus standard tacrolimus and methotrexate in patients with hematologic malignancies undergoing MMUD RIC HSCT. We report outcomes for 45 study patients: 40 (89%) 1-locus and five (11%) 2-loci mismatches (HLA-A, -B, -C, -DRB1, or -DQB1), with a median of 36.5 months (range, 17.4 to 59.6 months) follow-up.The 180-day cumulative incidence of grade 2 to 4 acute GVHD was 22% (95% CI, 11% to 35%). One-year cumulative incidence of chronic GVHD was 29% (95% CI, 16% to 43%). Two-year cumulative incidences of nonrelapse mortality (NRM) and relapse were 11% (95% CI, 4% to 22%) and 38% (95% CI, 24% to 52%), respectively. Two-year progression-free survival and overall survival were 51% (95% CI, 36% to 64%) and 64% (95% CI, 49% to 76%), respectively. Bortezomib-treated HLA-mismatched patients experienced rates of NRM, acute and chronic GVHD, and survival similar to those of contemporaneous HLA-matched RIC HSCT at our institution. Immune recovery, including CD8(+) T-cell and natural killer cell reconstitution, was enhanced with bortezomib.A novel short-course, bortezomib-based GVHD regimen can abrogate the survival impairment of MMUD RIC HSCT, can enhance early immune reconstitution, and appears to be suitable for prospective randomized evaluation.
A chemokine-to-cytokine-to-chemokine cascade critical in antiviral defense
Authors: Thais P. Salazar-Mather, Thomas A. Hamilton, Christine A. Biron
Journal: Journal of Clinical Investigation (2000)

Macrophage inflammatory protein 1α (MIP-1α) promotes natural killer (NK) cell inflammation in livers during murine cytomegalovirus (MCMV) infections, and NK cell–produced interferon γ (IFN-γ) contributes to defense against MCMV infections. A specific role for local NK cell IFN-γ production, however, has not been established. The importance of MIP-1α and NK cell–produced IFN-γ in shaping endogenous immune responses and defense in different compartments was examined. MIP-1α deficiency profoundly decreased resistance to MCMV and was associated with dramatically reduced NK cell accumulation and IFN-γ production in liver. MIP-1α–independent IFN-γ responses were observed in serum and spleen, and infection-induced elevations in blood NK cell populations occurred in absence of the factor, but peak liver expression of another chemokine, the monokine induced by IFN-γ (Mig), depended upon presence of MIP-1α, NK cells, and IFN-γ. The Mig response was also important for viral resistance. Thus, serum cytokine responses are insufficient; MIP-1α is critical for NK cell migration and IFN-γ delivery to mediate protection; and Mig induction in tissues is a downstream protective response resulting from the process. These results define a critical chemokine-to-cytokine-to-chemokine cascade required for defense during a viral infection establishing itself in tissues.
Defining Insulin Resistance From Hyperinsulinemic-Euglycemic Clamps
Authors: Charmaine S. Tam, Wenting Xie, William D. Johnson, William T. Cefalu, Leanne M. Redman, Eric Ravussin
Journal: Diabetes Care (2012)

This study was designed to determine a cutoff point for identifying insulin resistance from hyperinsulinemic-euglycemic clamp studies performed at 120 mU/m(2)·min in a white population and to generate equations from routinely measured clinic and blood variables for predicting clamp-derived glucose disposal rate (GDR), i.e., insulin sensitivity.We assembled data from hyperinsulinemic-euglycemic clamps (120 mU/m(2)·min insulin dose) performed at the Pennington Biomedical Research Center between 2001 and 2011. Subjects were divided into subjects with diabetes (n = 51) and subjects without diabetes (n = 116) by self-report and/or fasting glucose ≥126 mg/dL.We found that 75% of individuals with a GDR <5.6 mg/kg fat-free mass (FFM) + 17.7·min were truly insulin resistant. Cutoff values for GDRs normalized for body weight, body surface area, or FFM were 4.9 mg/kg·min, 212.2 mg/m(2)·min, and 7.3 mg/kgFFM·min, respectively. Next, we used classification tree models to predict GDR from routinely measured clinical and biochemical variables. We found that individual insulin resistance could be estimated with good sensitivity (89%) and specificity (67%) from the homeostasis model assessment of insulin resistance (HOMA-IR) >5.9 or 2.8< HOMA-IR <5.9 with HDL <51 mg/dL.We developed a cutoff for defining insulin resistance from hyperinsulinemic-euglycemic clamps. Moreover, we now provide classification trees for predicting insulin resistance from routinely measured clinical and biochemical markers. These findings extend the clamp from a research tool to providing a clinically meaningful message for participants in research studies, potentially providing greater opportunity for earlier recognition of insulin resistance.
Transcription and Evolutionary Dynamics of the Centromeric Satellite Repeat CentO in Rice
Authors: Hye-Ran Lee, Pavel Neumann, Jiri Macas, Jiming Jiang
Journal: Molecular Biology and Evolution (2006)

Satellite DNA is a major component of centromeric heterochromatin in most multicellular eukaryotes, where it is typically organized into megabase-sized tandem arrays. It has recently been demonstrated that small interfering RNAs (siRNAs) processed from centromeric satellite repeats can be involved in epigenetic chromatin modifications which appear to underpin centromere function. However, the structural organization and evolution of the centromeric satellite DNA is still poorly understood. We analyzed the centromeric satellite repeat arrays from rice chromosomes 1 and 8 and identified higher order structures and local homogenization of the CentO repeats in these 2 centromeres. We also cloned the CentO repeats from the CENH3-associated nucleosomes by a chromatin immunoprecipitation (ChIP)–based method. Sequence variability analysis of the ChIPed CentO repeats revealed a single variable domain within the repeat. We detected transcripts derived from both strands of the CentO repeats. The CentO transcripts are processed into siRNA, suggesting a potential role of this satellite repeat family in epigenetic chromatin modification.