tbuckley/cabot-search huggingface dataset:
Identification of a unique tumor antigen as rejection antigen by molecular cloning and gene transfer.
Authors: H J Stauss, C Van Waes, M A Fink, B Starr, H Schreiber
Journal: The Journal of Experimental Medicine (1986)

Tumor-specific transplantation antigens are antigens that can lead to complete immunological destruction of a transplanted cancer by the syngeneic host. When such antigens are expressed on cancers induced by chemical or physical carcinogens, then they are usually unique, i.e., antigenically different for each independently induced tumor. In this study, we show that the product of a gene encoding a novel MHC class I molecule and isolated from the murine UV light-induced regressor tumor 1591 represents one such unique tumor-specific transplantation antigen that causes tumor rejection. The major evidence comes from our finding that 1591 progressor variants regularly lost the gene encoding this antigen that is expressed in the parental tumor that regresses in normal mice; furthermore, reintroduction of this gene into a 1591 progressor variant by DNA transfection caused the progressor variant to regress in normal immunocompetent mice. Thus, the progressor tumor reverted to the parental regressor phenotype following transfection. Consistent with the conclusion that the expression of the novel MHC class I gene following transfection was responsible for the regressor phenotype is also our finding that a variant of the transfected tumor that had lost expression of the transfected gene resumed its progressive growth behavior. Finally, we show that the molecule encoded by the novel class I gene is specifically recognized by a syngeneic tumor-specific cytolytic T cell clone that we have previously shown to select in vitro for progressor variants from the parental regressor tumor cell line. It remains to be determined to what extent unique tumor-specific rejection antigens of other highly immunogenic regressor tumors are encoded by novel MHC class I genes and whether these genes represent germline mutations or somatic mutations caused by the carcinogen treatment.
Microvillous surface area in secondary disaccharidase deficiency.
Authors: A D Phillips, S Avigad, J Sacks, S J Rice, N E France, J A Walker-Smith
Journal: Gut (1980)

Electron microscopy was used to measure microvillous surface area in seven small intestinal biopsies showing secondary disaccharidase deficiency and in five biopsies having normal disaccharidase levels. There were significant reductions in microvillous surface area in the enzyme deficient group, although the microvilli were not severely damaged. Histological abnormality was not always present with disaccharidase deficiency. There was no significant difference in intraepithelial lymphocyte counts between the two groups.
Balancing ovulation and anovulation: integration of the reproductive and energy balance axes by neuropeptides
Authors: J. J. Evans, G. M. Anderson
Journal: Human Reproduction Update (2012)

Because of the substantial energy demands of reproduction, the brain must temper the fertility of individuals to match nutritional availability. Under-nutrition is associated with infertility in humans and animals. The brain uses adipose- and gut-derived hormones, such as leptin, insulin and ghrelin, to modulate the activity of the GnRH neuronal network that drives reproduction. It is becoming clear that there are both direct and indirect pathways acting on GnRH neurones. A PubMed search was performed using keywords associated with neuropeptides and metabolic hormones that are associated with reproductive and energy balance axes. Evidence that neurones which produce galanin, galanin-like peptide, kisspeptin, alpha-melanocyte-stimulating hormone, neuropeptide Y and oxytocin convey metabolic information to the reproductive axis is presented. The extent to which these neurones express receptors for metabolic hormones is variable but interactions between them allows for complex intermingling of information. Available metabolic fuels modulate hormone input to these neurones, leading in turn to altered GnRH release and appropriate drive to the gonads. The consequent change in sex steroid production is likely to contribute to co-ordination of the network. We hypothesize that the absence of an estrogenic milieu during anovulation compared with presence of estradiol during follicular maturation is important for the regulation of most of the neuropeptides. An improved understanding of the normal responses to energy deprivation may also help to identify novel therapeutic targets for infertility that often accompanies metabolic disorders, such as diabetes, obesity and polycystic ovary syndrome.
Efficacy of peginterferon and ribavirin is associated with the IL28B gene in Korean patients with chronic hepatitis C
Authors: Seok Hoo Jeong, Young Kul Jung, Jae Won Yang, Sang Jin Park, Jong Woo Kim, Oh Sang Kwon, Yun Soo Kim, Duck Joo Choi, Ju Hyun Kim
Journal: Clinical and Molecular Hepatology (2012)

Background/Aims Sustained virologic response (SVR) for the treatment of chronic hepatitis C (CHC) may differ with ethnicity due to differences in genetic traits. This study evaluated the efficacy of peginterferon and ribavirin, and the association between IL28B genotypes and the treatment efficacy in Korean CHC patients. Methods This was a retrospective cohort study using data from medical records. Eighty-five CHC patients were eligible for assessment of the efficacy of antiviral therapy, and 47 patients were available for an IL28B genetic study, which was performed using the Multiplex tetra-primer PCR method for rs12979860. Results Overall, the early virologic response rate was 87.1%: 84.9% in HCV genotype 1 and 90.6% in genotype 2. The overall end-of-treatment virologic response rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. The overall SVR rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. For rs12979860, the frequencies of polymorphisms were 89% for the CC type, 11% for the CT type, and 0% for the TT type. Their overall SVR rate was 87% (39/47): 90.5% (38/42) for the CC type and 20% (1/5) for the CT type. For genotype 1, SVR rates were 88% (21/24) for the CC type and 0% (0/4) for the CT type. Multivariate analysis revealed that the IL28B-CC type was a good predictor for SVR. Conclusions The SVR of the combination therapy in Koreans was higher than that observed in Western countries. This finding might be attributable to the high prevalence of IL28B-CC type among Koreans, which may be a good predictor of SVR. Keywords: Chronic hepatitis C; Peginterferon; Ribavirin; IL28B; Korea
A second study of tensile fatigue properties of human articular cartilage.
Authors: B Weightman, D J Chappell, E A Jenkins
Journal: Annals of the Rheumatic Diseases (1978)

The tensile fatigue properties of the collagen fibre meshwork in normal human articular cartilage were measured by subjecting isolated specimens of post-mortem femoral head cartilage to cyclic tensile stress. The results of the study showed (1) that the collagen fibre meshwork is fatigue prone and (2) that its fatigue strength decreases rapidly with age. Extrapolation of the data to physiologically possible stress levels suggests that tensile fatigue failure of the collagen meshwork could occur in life.
Breast-Feeding and Childhood-Onset Type 1 Diabetes
Authors: Chris R. Cardwell, Lars C. Stene, Johnny Ludvigsson, Joachim Rosenbauer, Ondrej Cinek, Jannet Svensson, Francisco Perez-Bravo, Anjum Memon, Suely G. Gimeno, Emma J.K. Wadsworth, Elsa S. Strotmeyer, Michael J. Goldacre, Katja Radon, Lee-Ming Chuang, Roger C. Parslow, Amanda Chetwynd, Kyriaki Karavanaki, Girts Brigis, Paolo Pozzilli, Brone UrbonaitĖ, Edith Schober, Gabriele Devoti, Sandra Sipetic, Geir Joner, Constantin Ionescu-Tirgoviste, Carine E. de Beaufort, Kirsten Harrild, Victoria Benson, Erkki Savilahti, Anne-Louise Ponsonby, Mona Salem, Samira Rabiei, Chris C. Patterson
Journal: Diabetes Care (2012)

To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders.Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies.Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I(2) = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I(2) = 0%). Adjustments for potential confounders altered these estimates very little.The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.
Preferential sensitivity of the left canine purkinje system to cardiac glycosides.
Authors: J Reiser, G J Anderson
Journal: Circulation Research (1981)

Previous studies have shown that the toxic effects of cardiac glycosides are not manifested uniformly throughout the myocardium. The purpose of our study was to determine whether cardiac glycosides exert different effects on the right vs. left peripheral Purkinje systems and to ascertain mechanisms involved. Control in vitro measurements of paired right and left canine Purkinje fibers showed higher spontaneous rates in left (24.2 +/- 1.75 beats/min) than in right (11.6 +/- 1.55 beats/min, P less than 0.01, n = 81) Purkinje fiber bundles. Following overdrive stimulation, left Purkinje fiber bundles also showed earlier escape beats. After ouabain exposure (2 X 10-7 M), left Purkinje fiber bundles showed earlier signs of toxicity in 20 of 28 experiments, as determined by changes in the maximum diastolic potential, the degree of diastolic depolarization, spontaneous escape intervals, and the magnitude of delayed after-depolarizations. The enhanced sensitivity of left Purkinje fiber bundles was independent of the extracellular potassium concentration and glycoside polarity, and was also observed in situ. We conclude that distal Purkinje fibers are functionally dissimilar and that the left Purkinje system shows greater sensitivity to cardiac glycosides than the right Purkinje system. These data also support the observation that digitalis-induced dysrhythmias arise in the left ventricle.
Clarifying process versus structure in human intelligence: Stop talking about fluid and crystallized
Authors: Wendy Johnson, Irving I. Gottesman
Journal: Behavioral and Brain Sciences (2006)

Blair presumes the validity of the fluid-crystallized model throughout his article. Two comparative evaluations recently demonstrated that this presumption can be challenged. The fluid-crystallized model offers little to the understanding of the structural manifestation of general intelligence and other more specific abilities. It obscures important issues involving the distinction of pervasive learning disabilities (low general intelligence) from specific, content-related disabilities that impede the development of particular skills.
Virus-induced Transient Bone Marrow Aplasia: Major Role of Interferon-α/β during Acute Infection with the Noncytopathic Lymphocytic Choriomeningitis Virus
Authors: Daniel Binder, Jörg Fehr, Hans Hengartner, Rolf M. Zinkernagel
Journal: The Journal of Experimental Medicine (1997)

The hematologic consequences of infection with the noncytopathic lymphocytic choriomeningitis virus (LCMV) were studied in wild-type mice with inherent variations in their interferon (IFN)-α/β responder ability and in mutant mice lacking α/β (IFN-α/β R0/0) or γ IFN (IFN-γ R0/0) receptors. During the first week of infection, wild type mice demonstrated a transient pancytopenia. Within a given genetic background, the extent of the blood cell abnormalities did not correlate with the virulence of the LCMV isolate but variations were detected between different mouse strains; they were found to depend on their IFN-α/β responder phenotype. Whereas IFN-γ R0/0 mice were comparable to wild-type mice, IFN-α/β R0/0 mice exhibited unchanged peripheral blood values during acute LCMV infection. In parallel, the bone marrow (BM) cellularity, the pluripotential and committed progenitor compartments were up to 30-fold reduced in wild type and IFN-γ R0/0, but remained unchanged in IFN-α/β R0/0 mice. Viral titers in BM 3 d after LCMV infection were similar in these mice, but antigen localization was different. Viral antigen was predominantly confined to stromal BM in normal mice and IFN-γ R0/0 knockouts, whereas, in IFN-α/β R0/0 mice, LCMV was detected in &amp;gt;90% of megakaryocytes and 10–15% of myeloid precursors, but not in erythroblasts. Although IFN-α/β efficiently prevented viral replication in potentially susceptible hematopoietic cells, even in overwhelming LCMV infection, unlimited virus multiplication in platelet and myeloid precursors in IFN-α/β R0/0 mice did not interfere with the number of circulating blood cells. Natural killer (NK) cell expansion and activity in the BM was comparable on day 3 after infection in mutant and control mice. Adaptive immune responses did not play a major role because comparable kinetics of LCMV-induced pancytopenia and transient depletion of the pluripotential and committed progenitor compartments were observed in CD80/0 and CD40/0 mice, in mice depleted of NK cells, in lpr mice, and in perforin-deficient (P0/0) mice lacking lytic NK cells. Thus, the reversible depression of hematopoiesis during early LCMV infection was not mediated by LCMV-WE–specific cytotoxic T lymphocyte, cytolysis, or secreted IFN-γ from virally induced NK cells but was a direct effect of IFN-α/β.
Mapping autism and schizophrenia onto the ontogenesis of social behaviour: A hierarchical-developmental rather than diametrical perspective
Authors: Ralf-Peter Behrendt
Journal: Behavioral and Brain Sciences (2008)

Abstract Co-morbidity of schizophrenia and autism is low because interpersonal concerns of schizophrenic patients presuppose developmental achievements that are absent in autism. Autism may arise if primary anxiety is not overcome at a key developmental stage by affective synchronisation between infant and caregiver. Schizophrenic patients will have learned to regulate primitive anxiety by affectively attuning to narrow social networks but remain highly vulnerable to exclusion from larger groups.
NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo
Authors: Jason L. Eriksen, Sarah A. Sagi, Tawnya E. Smith, Sascha Weggen, Pritam Das, D.C. McLendon, Victor V. Ozols, Kevin W. Jessing, Kenton H. Zavitz, Edward H. Koo, Todd E. Golde
Journal: Journal of Clinical Investigation (2003)

Epidemiologic studies demonstrate that long-term use of NSAIDs is associated with a reduced risk for the development of Alzheimer disease (AD). In this study, 20 commonly used NSAIDs, dapsone, and enantiomers of flurbiprofen were analyzed for their ability to lower the level of the 42-amino-acid form of amyloid beta protein (Abeta42) in a human H4 cell line. Thirteen of the NSAIDs and the enantiomers of flurbiprofen were then tested in acute dosing studies in amyloid beta protein precursor (APP) transgenic mice, and plasma and brain levels of Abeta and the drug were evaluated. These studies show that (a). eight FDA-approved NSAIDs lower Abeta42 in vivo, (b). the ability of an NSAID to lower Abeta42 levels in cell culture is highly predicative of its in vivo activity, (c). in vivo Abeta42 lowering in mice occurs at drug levels achievable in humans, and (d). there is a significant correlation between Abeta42 lowering and levels of ibuprofen. Importantly, flurbiprofen and its enantiomers selectively lower Abeta42 levels in broken cell gamma-secretase assays, indicating that these compounds directly target the gamma-secretase complex that generates Abeta from APP. Of the compounds tested, meclofenamic acid, racemic flurbiprofen, and the purified R and S enantiomers of flurbiprofen lowered Abeta42 levels to the greatest extent. Because R-flurbiprofen reduces Abeta42 levels by targeting gamma-secretase and has reduced side effects related to inhibition of cyclooxygenase (COX), it is an excellent candidate for clinical testing as an Abeta42 lowering agent.
DRUG-WITHDRAWAL PSYCHOSES
Authors: I. PIERCE JAMES
Journal: American Journal of Psychiatry (1963)

Three patients who developed drugwithdrawal psychoses clinically resembling delirium tremens two to three days after admission to a general hospital are described. All three had been addicted to a hypnotic drug (chloral hydrate, carbromal and sodium pentabarbital respectively) prior to admission but had not been taking alcohol. It is suggested that the syndrome of delirium tremens results from the association of a confusional psychosis with the alcohol (or sedative-drug) withdrawal syndrome and that the tremulous withdrawal psychosis of sedative drug addiction and the delirium tremens of alcoholism are clinically identical.
Development of cimetidine resistance in the Zollinger-Ellison syndrome.
Authors: B N Andersen, N E Larsen, S J Rune, H Worning
Journal: Gut (1985)

A patient with the Zollinger-Ellison syndrome was followed with multiple gastric secretion tests and serum gastrin analyses for six years. During this period cimetidine requirement increased to a daily dose of 8 g, but it reversed spontaneously after two years. The altered cimetidine effectiveness was not associated with reduced oral bioavailability and serum calcium was unchanged. Total serum gastrin was very high at all times, and fractionation of gastrins in serum by gel filtration showed varying proportion of big to small gastrins, but not in a mode which explained the parietal cell resistance to cimetidine.
Nitric oxide as an antimicrobial agent: does NO always mean NO?
Authors: P VALLANCE, I CHARLES
Journal: Gut (1998)

See article on page 334 

Nitric oxide (NO) synthesised from l-arginine subserves multiple physiological functions in the cardiovascular, respiratory, gastrointestinal, genitourinary, and central and peripheral nervous systems.1 But synthesis of NO also contributes to host defence and seems to have cytostatic and cytotoxic effects against certain pathogens, and even against host cells themselves.1 How is this double act achieved? What determines the switch from physiological mediator to lethal gas and how is bacterial killing achieved?

The simple and standard answer to the dual action of NO is that its effects depend on the amounts generated and the local concentrations achieved. In the nanomolar concentrations generated by constitutive NO synthase (NOS) isoforms, NO acts as a cell signalling molecule and interacts preferentially with its physiological target enzymes—the most significant of which seem to be soluble guanylyl cyclase and possibly cytochrome C oxidase. At the higher concentrations generated when the other enzymes become targets for NO action the cytokine induced isoform of NOS (iNOS) is expressed in cells. Haem containing enzymes, enzymes with Fe-S clusters including aconitase, NADH dehydrogenase and succinate dehydrogenase, the non-haem metalloenzymes, ribonucleotide reductase and DNA itself are all susceptible to inhibition or damage when NO output is high. Consistent with this high versus low output explanation, soluble guanylyl cyclase and cytochrome C oxidase are reversibly affected by NO (stimulation and inhibition respectively) with near maximal effects occurring in the nanomolar range of NO concentrations whereas effects on other enzymes occur only in the micromolar range and are often irreversible.

Despite the simplicity and attractiveness of the low versus high output theory, it is almost certainly only partially correct. Many reports indicate that organisms which seem to be killed following induction of the l-arginine/NO pathway in immune cells are resistant to the effects of NO …
A randomized study of interferon-α versus interferon-α and low-dose arabinosyl cytosine in chronic myeloid leukemia
Authors: Michele Baccarani, Gianantonio Rosti, Antonio de Vivo, Francesca Bonifazi, Domenico Russo, Giovanni Martinelli, Nicoletta Testoni, Marilina Amabile, Mauro Fiacchini, Enrico Montefusco, Giuseppe Saglio, Sante Tura
Journal: Blood (2002)
Adverse Outcomes of Tacrolimus Withdrawal in Immune–Quiescent Kidney Transplant Recipients
Authors: Donald E Hricik, Richard N Formica, Peter Nickerson, David Rush, Robert L Fairchild, Emilio D Poggio, Ian W Gibson, Chris Wiebe, Kathryn Tinckam, Suphamai Bunnapradist, Milagros Samaniego-Picota, Daniel C Brennan, Bernd Schröppel, Osama Gaber, Brian Armstrong, David Ikle, Helena Diop, Nancy D Bridges, Peter S Heeger
Journal: Journal of the American Society of Nephrology (2015)

Concerns about adverse effects of calcineurin inhibitors (CNIs) have prompted development of protocols that minimize their use. Whereas previous CNI withdrawal trials in heterogeneous cohorts showed unacceptable rates of acute rejection (AR), we hypothesized that we could identify individuals capable of tolerating CNI withdrawal by targeting immunologically quiescent kidney transplant recipients. The Clinical Trials in Organ Transplantation-09 Trial was a randomized, prospective study of nonsensitized primary recipients of living donor kidney transplants. Subjects received rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil, and prednisone. Six months post-transplantation, subjects without de novo donor-specific antibodies (DSAs), AR, or inflammation at protocol biopsy were randomized to wean off or remain on tacrolimus. The intended primary end point was the change in interstitial fibrosis/tubular atrophy score between implantation and 24-month protocol biopsies. Serially collected urine CXCL9 ELISA results were correlated with outcomes. The study was terminated prematurely because of unacceptable rates of AR (4 of 14) and/or de novo DSAs (5 of 14) in the tacrolimus withdrawal arm. Positive urinary CXCL9 predated clinical detection of AR by a median of 15 days. Analyses showed that >16 HLA-DQ epitope mismatches and pretransplant, peripheral blood, donor-reactive IFN-γ ELISPOT assay results correlated with development of DSAs and/or AR on tacrolimus withdrawal. Although data indicate that urinary CXCL9 monitoring, epitope mismatches, and ELISPOT assays are potentially informative, complete CNI withdrawal must be strongly discouraged in kidney transplant recipients who are receiving standard-of-care immunosuppression, including those who are deemed to be immunologically quiescent on the basis of current clinical and laboratory criteria.