tbuckley/cabot-search huggingface dataset:
Mannan-binding lectin deficiency results in unusual antibody production and excessive experimental colitis in response to mannose-expressing mild gut pathogens
Authors: S. Muller, T. Schaffer, B. Flogerzi, B. Seibold-Schmid, J. Schnider, K. Takahashi, A. Darfeuille-Michaud, E. Vazeille, A. M. Schoepfer, F. Seibold
Journal: Gut (2010)

In Crohn's disease (CD) the deficiency of mannan-binding lectin (MBL) is associated with an increased prevalence of anti-Saccharomyces cerevisiae antibodies (ASCA) and with complicated phenotypes of the disease. However, the role of MBL in intestinal inflammation is currently unclear. A study was undertaken to analyse local MBL expression in human intestine and the consequences of MBL deficiency in experimental colitis and yeast infection.ASCA were measured by ELISA. MBL was assessed by ELISA and quantitative PCR. Wild type and MBL-deficient mice were administered dextran sulfate sodium (DSS) in the presence or absence of viable Candida albicans or adhesive invasive Escherichia coli (AIEC). Mice were infected with C albicans to assess generation of anti-yeast mannan antibodies.MBL expression was virtually undetectable in the intestinal mucosa of both healthy controls and patients with CD, irrespective of macroscopic inflammation, indicating that systemic MBL must be responsible for the reduced risk of complicated disease in MBL-competent patients with CD. MBL-deficient mice showed enhanced DSS colitis upon oral challenge with C albicans or AIEC. C albicans could be recovered from the kidneys of colitic/C albicans-fed MBL-deficient, but not wild type mice. Infection with C albicans induced high titres of anti-C albicans mannan IgM and IgG in MBL-deficient mice but only a modest and transient IgM response with no class switch to IgG in wild type mice. Cross-reactive ASCA IgM continuously increased in MBL-deficient mice but rapidly declined after transient induction in wild type mice. In MBL-deficient mice, increased C albicans dissemination correlated with reduced early retention in the circulation.These results suggest that systemic MBL helps to prevent excessive inflammation upon access of normally mild pathogens across the damaged intestinal epithelium. Lack of this innate defence promotes antibody responses with cross-reactive potential against common mannan epitopes. These interpretations are compatible with the increased prevalence of ASCA and complicated disease phenotypes in MBL-deficient patients with CD.
Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot?
Authors: C T Moraes, F Ciacci, E Bonilla, C Jansen, M Hirano, N Rao, R E Lovelace, L P Rowland, E A Schon, S DiMauro
Journal: Journal of Clinical Investigation (1993)

We identified two patients with pathogenic single nucleotide changes in two different mitochondrial tRNA genes: the first mutation in the tRNA(Asn) gene, and the ninth known mutation in the tRNA(Leu(UUR)) gene. The mutation in tRNA(Asn) was associated with isolated ophthalmoplegia, whereas the mutation in tRNA(Leu(UUR)) caused a neurological syndrome resembling MERRF (myoclonus epilepsy and ragged-red fibers) plus optic neuropathy, retinopathy, and diabetes. Both mutations were heteroplasmic, with higher percentages of mutant mtDNA in affected tissues, and undetectable levels in maternal relatives. Analysis of single muscle fibers indicated that morphological and biochemical alterations appeared only when the proportions of mutant mtDNA exceeded 90% of the total cellular mtDNA pool. The high incidence of mutations in the tRNA(Leu(UUR)) gene suggests that this region is an "etiologic hot spot" in mitochondrial disease.
Induction of rat liver alkaline phosphatase: the mechanism of the serum elevation in bile duct obstruction
Authors: Marshall M. Kaplan, Adriana Righetti
Journal: Journal of Clinical Investigation (1970)

Bile duct ligation in the rat leads to a rapid increase in hepatic and serum alkaline phosphatase activity. Within 12 hr after bile duct ligation, hepatic alkaline phosphatase has increased 7-fold and serum alkaline phosphatase activity 2(1/2)-fold. The elevation in the serum activity is completely due to an increase in an isozyme that appears to originate in the liver. This serum isozyme and liver phosphatase, both partially purified by DEAE-cellulose column chromatography, have identical Michaelis constants, pH optima, and rates of heat denaturation. These isozymes migrate identically when subjected to electrophoresis on polyacrylamide gel, and their migration rates are equally slowed after neuraminidase digestion. The data suggest that the rise in hepatic alkaline phosphatase activity is dependent on de novo protein synthesis. Cycloheximide, in a dose that inhibited incorporation of leucine-(14)C into protein by 68%, inhibited the rise in liver phosphatase by 98% and that in serum by 80%. The rise in liver phosphatase activity could not be accounted for by simple retention of alkaline phosphatase that would normally appear in bile. The rise in liver activity after bile duct ligation was 240 times greater than the amount of phosphatase that normally appears in bile over a similar period of time. Cycloheximide had no effect on the bile duct ligation-induced changes in the serum and liver glutamic pyruvic transaminase.
Effect of breaking bad news on patients' perceptions of doctors
Authors: M. M Barnett
Journal: Journal of the Royal Society of Medicine (2002)

The breaking of bad news is a routine but difficult task for many health professionals.There are numerous anecdotes of insensitive practice but the subject has attracted little systematic research.We therefore interviewed 106 patients with advanced cancer (from an original sample of 195) to assess their perceptions of the doctors involved in their care.Aspects of the 'breaking bad news' event were recorded during discussion of the illness history and were subsequently rated.Participants were also asked to nominate doctors under the headings 'most helpful' and 'less helpful', and completed standardized psychological screening questionnaires.In 94 of the 106 cases the bad news had been given by a doctor, usually a surgeon.Of the 13 doctors categorized as 'most helpful' when breaking bad news, 8 were general practitioners; of the 7 categorized as 'less helpful' all were surgeons.69% of patients were neutral or positive about the bad-news consultation, but 20% were negative and 6% very negative.Doctors in surgical specialties were significantly more likely to be rated poorly than nonsurgical specialists or general practitioners.Surgeons were the group of doctors most likely to break bad news, but non-surgical doctors were rated more positively in performance of the task.This finding has implications for training.
Extrapolation of Measures of Work for Surveyed Services to Other Services
Authors: Nancy L. Kelly
Journal: JAMA (1988)

A national survey of physicians produced detailed data on the work involved in performing 372 different services. This article describes methods developed to extrapolate the study data to a larger universe of services, defined by the Physicians' Current Procedural Terminology, edition 4. Because data measuring work inputs for nonsurveyed services presently are unavailable, we devised an extrapolation method that makes use of available charge data without building their inherent distortions into the extrapolated scale. To neutralize the effect of these distortions, we used small, homogeneous families of services as the basic units for the extrapolations and assumed that charges are reasonable indicators of relative work within such families. To produce extrapolated work values within each family, we multiplied an estimate of work based on survey data for a benchmark procedure by charge-based ratios that represent the relationships between surveyed and nonsurveyed services. These extrapolations can be used in constructing a Resource-Based Relative Value Scale.
The U.S. Healthy People Initiative: Its Genesis and Its Sustainability
Authors: Lawrence W. Green, Jonathan Fielding
Journal: Annual Review of Public Health (2011)

Unlike most government initiatives in health, the Healthy People initiative of the U.S. federal government was crafted and sustained not as a federal initiative, but as a "national initiative" eliciting participation from nongovernmental national organizations, state health agencies, professional associations, multiple agencies of the U.S. Department of Health and Human Services, and other federal agencies, such as Agriculture, and increasingly engaging academia and state and local stakeholders in adapting the objectives for their own efforts to enact and evaluate state and local policies and programs. The quantified objectives at the center of the initiative were a product of continuous balancing of changing science and political or social concerns and priorities along with national and state or special population needs. The evolution from the first decade's objectives to each subsequent set of objectives reflected changing societal concerns, evidence-based technologies, theories, and discourses of those decades. Such accommodations changed the contours of the initiative over time in attempts to make it more relevant to specific partners and other stakeholders.
SINE Insertions as Clade Markers for Wild Crucifer Species
Authors: C. Tatout, S. Warwick, A. Lenoir, J-M Deragon
Journal: Molecular Biology and Evolution (1999)

Short interspersed nuclear elements (SINEs) are small noncoding transposable elements that are widespread in most eukaryotic genomes. Plant S1 SINEs are present in crucifers, especially in species of the Brassiceae tribe, and were generated by several waves of amplification of different evolutionary ages, suggesting that S1 insertional variability (presence/absence of an S1 at a given genomic site) could be used as a classification criterion to evaluate phylogenetic relationships. We applied this strategy on closely related species from the Brassica oleracea species complex using 21 independent S1 genomic sites. The microsatellite-like variation of S1 39 poly(A) tails was also used as a complementary classification criterion to obtain internal resolution in two different clades. The phylogenetic tree obtained by this approach is in general agreement with the classification made from chloroplast DNA restriction site polymorphisms and differs significantly from two other (nonequivalent) classifications made using nuclear restriction fragment length polymorphisms. Brassica incana, Brassica montana, and Brassica hilarionis are confirmed as the closest relatives of B. oleracea. From our data, we suggest that Brassica drepanensis emerged recently from a B. incana/Brassica villosa hybrid (with B. villosa as the maternal parent) following backcrosses to B. incana. We also detected several introgressions, confirming that these highly related species are capable of genetic exchange in their natural habitat. S1 markers are therefore very useful in understanding the detailed evolutionary history of wild Brassica species and could also be used to identify potential gene flow between cultivated (including transgenic) Brassica and their wild relatives.
Pharmacogenomic and Structural Analysis of Constitutive G Protein–Coupled Receptor Activity
Authors: Martine J. Smit, Henry F. Vischer, Remko A. Bakker, Aldo Jongejan, Henk Timmerman, Leonardo Pardo, Rob Leurs
Journal: The Annual Review of Pharmacology and Toxicology (2006)

G protein–coupled receptors (GPCRs) respond to a chemically diverse plethora of signal transduction molecules. The notion that GPCRs also signal without an external chemical trigger, i.e., in a constitutive or spontaneous manner, resulted in a paradigm shift in the field of GPCR pharmacology. The discovery of constitutive GPCR activity and the fact that GPCR binding and signaling can be strongly affected by a single point mutation drew attention to the evolving area of GPCR pharmacogenomics. For a variety of GPCRs, point mutations have been convincingly linked to human disease. Mutations within conserved motifs, known to be involved in GPCR activation, might explain the properties of some naturally occurring, constitutively active GPCR variants linked to disease. In this review, we provide a brief historical introduction to the concept of constitutive receptor activity and the pharmacogenomic and structural aspects of constitutive receptor activity.
THE PREVENTION OF THE SPREAD OF EPIDEMIC DISEASE AT SCHOOLS
Authors: H. M. Fletcher
Journal: BMJ (1918)

Gunshot wound of left knee.Entrance on inner side, frac- turing anterior aspect of femoral articular surface.There is also simple fracture of middle of shaft of femur, without direct relation to gunshot wound.Transfer notes say: "Arthritis purulenta, plilegmon incipiens; arthrotomia facta."Tube and gauze in. the joint on admission.June 8th, tube and gauze removed '-transverse inicision -above patelia; joint -"very septic."No drains of any sort inserted..The limb fixed on a W'allace-Maybury splint and elevated.
A Review of Smoking in Pregnancy: Effects on Pregnancy Outcomes and Cessation Efforts
Authors: R. Louise Floyd, Barbara K. Rimer, Gary A. Giovino, Patricia D. Mullen, Susan E. Sullivan
Journal: Annual Review of Public Health (1993)

In recent decades, there has been remarkable growth in scientific research examining the multiple ways in which racism can adversely affect health. This interest has been driven in part by the striking persistence of racial/ethnic inequities in health and ...Read More
Combined Dendritic Cell Cryotherapy of Tumor Induces Systemic Antimetastatic Immunity
Authors: Arthur Machlenkin, Ofir Goldberger, Boaz Tirosh, Adrian Paz, Ilan Volovitz, Erez Bar-Haim, Sung-Hyung Lee, Ezra Vadai, Esther Tzehoval, Lea Eisenbach
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Cryotherapy of localized prostate, renal, and hepatic primary tumors and metastases is considered a minimally invasive treatment demonstrating a low complication rate in comparison with conventional surgery. The main drawback of cryotherapy is that it has no systemic effect on distant metastases. We investigated whether intratumoral injections of dendritic cells following cryotherapy of local tumors (cryoimmunotherapy) provides an improved approach to cancer treatment, combining local tumor destruction and systemic anticancer immunity. Experimental Designs: The 3LL murine Lewis lung carcinoma clone D122 and the ovalbumin-transfected B16 melanoma clone MO5 served as models for spontaneous metastasis. The antimetastatic effect of cryoimmunotherapy was assessed in the lung carcinoma model by monitoring mouse survival, lung weight, and induction of tumor-specific CTLs. The mechanism of cryoimmunotherapy was elucidated in the melanoma model using adoptive transfer of T cell receptor transgenic OT-I CTLs into the tumor-bearing mice, and analysis of Th1/Th2 responses by intracellular cytokine staining in CD4 and CD8 cells. Results: Cryoimmunotherapy caused robust and tumor-specific CTL responses, increased Th1 responses, significantly prolonged survival and dramatically reduced lung metastasis. Although intratumor administration of dendritic cells alone increased the proliferation rate of CD8 cells, only cryoimmunotherapy resulted in the generation of effector memory cells. Furthermore, cryoimmunotherapyprotected mice that had survived primary MO5 tumors from rechallenge with parental tumors. Conclusions: These results present cryoimmunotherapy as a novel approach for systemic treatment of cancer. We envisage that cryotherapy of tumors combined with subsequent in situ immunotherapy by autologous unmodified immature dendritic cells can be applied in practice.
Medical Evidence of Human Rights Violations against Non-Arabic-Speaking Civilians in Darfur: A Cross-Sectional Study
Authors: Alexander C. Tsai, Mohammed A. Eisa, Sondra S. Crosby, Susannah Sirkin, Michele Heisler, Jennifer Leaning, Vincent Iacopino
Journal: PLoS Medicine (2012)

Alexander Tsai and colleagues review medical records from the Amel Centre, Sudan, to assess consistency between recorded medical evidence and patient reports of human rights violations by the Government of Sudan and Janjaweed forces.
Does Ca/Mg-free medium have an effect on the survival of the preimplantation mouse embryo after biopsy?
Authors: J Santalo
Journal: Human Reproduction Update (1996)

The way in which the different technical aspects of clinical preimplantation genetic diagnosis affect the survival of the biopsied embryos is not well understood. One of these aspects is the influence of Ca2+/Mg2+-free medium on the developmental capacity of the biopsied embryo and the biopsied cell itself. Therefore, we used an experimental design involving 4-cell mouse embryos to evaluate the effect of performing the biopsy procedure under such conditions. Our results indicate that the use of Ca2+/Mg2+-free medium has no detrimental effect (at least in mouse embryos) on the viability of the biopsied embryos and their biopsied cells when used during relatively short times of exposure. Keywords: Ca2+/Mg2+-free medium/preimplantation diagnosis
Diabetes Exacerbates Inflammatory Responses to Ischemia-Reperfusion
Authors: Julián Panés, Iwao Kurose, M. Dolores Rodriguez-Vaca, Donald C. Anderson, Masayuki Miyasaka, Patrick Tso, D. Neil Granger
Journal: Circulation (1996)

Background Diabetes is associated with an increased incidence of ischemic organ damage. The objectives of present study were to compare the leukocyte–endothelial cell adhesive interactions and albumin leakage response of mesenteric venules to ischemia-reperfusion between control rats, rats with streptozotocin-induced diabetes, and rats with hyperglycemia induced by glucose infusion and to define the molecular determinants of the leukocyte accumulation elicited by ischemia-reperfusion in diabetic rats. Methods and Results Under baseline conditions, lower venular shear rates and an increased number of rolling leukocytes were noted in diabetic rats, whereas the number of adherent and emigrated leukocytes did not differ from that in control rats. Spontaneous albumin leakage from mesenteric venules was markedly increased in diabetic rats but not in hyperglycemic nondiabetic rats. Ischemia-reperfusion elicited significantly larger increases in leukocyte adhesion and emigration and albumin leakage in diabetic rats. Acute elevation of glucose levels did not modify the microvascular responses to ischemia-reperfusion compared with control rats. Antibodies directed against CD11/CD18, intercellular adhesion molecule–1 (ICAM-1), or P-selectin but not l -selectin significantly decreased the number of adherent and emigrated leukocytes after ischemia-reperfusion in diabetic rats. However, none of the antibodies significantly attenuated the increased albumin leakage response to ischemia-reperfusion in diabetic rats. Conclusions Thes results indicate that diabetes mellitus is associated with exaggerated leukocyte–endothelial cell adhesion and albumin leakage responses to ischemia-reperfusion. The enhanced leukocyte accumulation in response to ischemia-reperfusion is mediated by CD11/CD18–ICAM-1 interactions (firm adhesion) and P-selectin (rolling). The exaggerated albumin leakage response to ischemia-reperfusion in diabetics is not mediated by the recruited inflammatory cells.
Molecular basis of hepatic carnitine palmitoyltransferase I deficiency.
Authors: L IJlst, H Mandel, W Oostheim, J P Ruiter, A Gutman, R J Wanders
Journal: Journal of Clinical Investigation (1998)

Mitochondrial fatty acid beta-oxidation is important for energy production, which is stressed by the different defects found in this pathway. Most of the enzyme deficiencies causing these defects are well characterized at both the protein and genomic levels. One exception is carnitine palmitoyltransferase I (CPT I) deficiency, of which until now no mutations have been reported although the defect is enzymatically well characterized. CPT I is the key enzyme in the carnitine-dependent transport across the mitochondrial inner membrane and its deficiency results in a decreased rate of fatty acid beta-oxidation. Here we report the first delineation of the molecular basis of hepatic CPT I deficiency in a new case. cDNA analysis revealed that this patient was homozygous for a missense mutation (D454G). The effect of the identified mutation was investigated by heterologous expression in yeast. The expressed mutant CPT IA displayed only 2% of the activity of the expressed wild-type CPT IA, indicating that the D454G mutation is the disease-causing mutation. Furthermore, in patient's fibroblasts the CPT IA protein was markedly reduced on immunoblot, suggesting that the mutation renders the protein unstable.
Combined Transcriptional and Translational Targeting of EWS/FLI-1 in Ewing's Sarcoma
Authors: Silvia Mateo-Lozano, Prafulla C. Gokhale, Viatcheslav A. Soldatenkov, Anatoly Dritschilo, Oscar M. Tirado, Vicente Notario
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To show the efficacy of targeting EWS/FLI-1 expression with a combination of specific antisense oligonucleotides and rapamycin for the control of Ewing's sarcoma (EWS) cell proliferation in vitro and the treatment of mouse tumor xenografts in vivo. Experimental Design: EWS cells were simultaneously exposed to EWS/FLI-1–specific antisense oligonucleotides and rapamycin for various time periods. After treatment, the following end points were monitored and evaluated: expression levels of the EWS/FLI-1 protein, cell proliferation, cell cycle distribution, apoptotic cell death, caspase activation, and tumor growth in EWS xenografts implanted in nude mice. Results: Simultaneous exposure of EWS cells in culture to an EWS/FLI-1–targeted suppression therapy using specific antisense oligonucleotides and rapamycin resulted in the activation of a caspase-dependent apoptotic process that involved the restoration of the transforming growth factor-β–induced proapoptotic pathway. In vivo, individual administration of either antisense oligonucleotides or rapamycin significantly delayed tumor development, and the combined treatment with antisense oligonucleotides and rapamycin caused a considerably stronger inhibition of tumor growth. Conclusions: Concurrent administration of EWS/FLI-1 antisense oligonucleotides and rapamycin efficiently induced the apoptotic death of EWS cells in culture through a process involving transforming growth factor-β. In vivo experiments conclusively showed that the combined treatment with antisense oligonucleotides and rapamycin caused a significant inhibition of tumor growth in mice. These results provide proof of principle for further exploration of the potential of this combined therapeutic modality as a novel strategy for the treatment of tumors of the Ewing's sarcoma family.