tbuckley/cabot-search huggingface dataset:
Treatment of Pediculosis Capitis
Authors: E. Blackstock
Journal: BMJ (1944)

The incidence of agglutinins for Proteus OX 19, OX 2, and OXK in the British population has rarely been investigated.It was reported in the Monthly Bulletin of the Emergency Public Health Laboratory Service (Aug., 1942, p. 6) that in 100 " normal " sera no agglutination was obtained with any of the three suspensions above 1/128 dilution.The titres for OXK were approximately double those found for OX 19 and OX 2, and it was suggested that titres of 1/80 or over with OX 19 are unlikely "in the absence of exposure, either recent or remote, to typhus infection."Approximately nine- tenths of these sera showed a titre of 1/16 or less with the OX 19 and OX 2 suspensions.There is only one report from this country on vaccination against typhus fever and its effects on the Weil-Felix reaction.Felix (1942), in a report to the Medical Research Council, gave briefly the alterations in the OX 19 agglutinin titre evoked by various vaccines.Considering 100% or greater increase in agglutinin titre as significant, very variable results were found with both the type and the batch of vaccine used.With vaccines of the Cox type the proportion showing a significant rise in titre varied with the batch of vaccine from approxi- mately 5 to 50%'. The Present InvestigationIn the investigation now reported a vaccine prepared by the Connaught Laboratories, Toronto, from a European louse- borne strain of Rickettsia prowazeki grown in the yolk-sac of chick embryos (Cox, 1938) was used.It was issued on Nov. 4, 1941, and with a batch of vaccine of the same date Felix obtained a significant increase in OX 19 agglutinin titre in about half of those inoculated.Twenty-three public health workers were vaccinated and their Weil-Felix and clinical reactions were investigated.At weekly intervals each received 0.25 c.cm., 0.5 c.cm., and 1 c.cm. of vaccine subcutaneously, and three months later a fourth dose of 1 c.cm.Samples of blood were obtained on four occasions: (1) before the first injection; (2) a fortnight after the third injection ; (3) before and (4) a fortnight after revaccination ; these were tested for OX 19, OX 2, and OXK agglutinins.The method used in the Weil-Felix test was as follows:Concentrated suspensions of OX 19, OX 2, and OXK, prepared at the Standards (M.R.C.) Laboratory, Oxford, were diluted 15 times and added in equal quantity to serial serum dilutions, the final dilutions of serum being 1/5, 1/10, 1/20, 1/40, 1/80, 1/160, 1/320, and 1/640, while that of the suspension was 1/30.All tubes were incubated at 56°C. for 4 hours, and the test was read after standing at room temperature overnight; the last tube showing standard agglutination was taken as the titre.
Integrating the Myocardial Matrix Into Heart Failure Recognition and Management
Authors: Francis G. Spinale, Michael R. Zile
Journal: Circulation Research (2013)

In contrast to public perception, the morbidity and mortality and the resultant healthcare costs associated with chronic heart failure (HF) are increasing and arguably reaching epidemic proportions. Although basic research efforts have provided unique insights into fundamental processes that govern myocardial extracellular matrix (ECM) growth and function, the translation of these findings to improved diagnostics and therapeutics for HF has not been as forthcoming. The factors that contribute to this relative paucity of new clinical tools for HF are multifactorial but likely include the need to recognize and differentiate HF phenotypes and to couple the use of biomarkers and multimodality imaging in early translational research studies. Recognizing the classification scheme of HF with a reduced ejection fraction (EF) to that of HF with a preserved EF and incorporating unique and differential measurements of ECM remodeling to these specific disease processes are warranted. For example, profiling pathways of ECM degradation such as the matrix metalloproteinases in patients with ischemic heart disease and HF with a reduced EF can provide prognostic information in terms of risk of progression to HF. In patients with chronic hypertensive disease and HF with a preserved EF, plasma profiling indexes of ECM synthesis and turnover, as well as advances in ECM imaging, have been shown to provide diagnostic and prognostic use. In terms of therapeutics, strategies to stabilize the ECM in HF with a reduced EF hold potential, whereas in contradistinction, selective antifibrotic agents may hold promise for HF with a preserved EF.
Multiple gestation and infertility treatment: registration, reflection and reaction—the Belgian project
Authors: Willem Ombelet, Petra De Sutter, Josiane Van der Elst, Guy Martens
Journal: Human Reproduction Update (2004)

Multiple pregnancies associated with infertility treatment are recognized as an adverse outcome and are responsible for morbidity and mortality related to prematurity and very low birthweight population. Due to the epidemic of iatrogenic multiple births, the incidence of maternal, perinatal and childhood morbidity and mortality has increased. This results in a hidden healthcare cost of infertility therapy and this may lead to social and political concern. Reducing the number of embryos transferred and the use of natural cycle IVF will surely decrease the number of multiple gestations. Consequently, optimized cryopreservation programmes will be essential. For non-IVF hormonal stimulation, responsible for more than one-third of all multiple pregnancies after infertility treatment, a strict ovarian stimulation protocol aiming at mono-ovulation is crucial. Multifetal pregnancy reduction is an effective method to reduce high order multiplets but carries its own risk of medical and emotional complications. Excellent data collection of all infertility treatments is needed in our discussion with policy makers. The Belgian project, in which reimbursement of assisted reproduction technology-related laboratory activities is linked to a transfer policy aiming at substantial multiple pregnancy reduction, is a good example of cost-efficient health care through responsible, well considered clinical practice.
Mapping the Lowe oculocerebrorenal syndrome to Xq24-q26 by use of restriction fragment length polymorphisms.
Authors: D N Silver, R A Lewis, R L Nussbaum
Journal: Journal of Clinical Investigation (1987)

A molecular linkage analysis of four large families with the Lowe oculocerebrorenal syndrome (LS) provided a subregional localization of LS to the distal long arm of the X chromosome at Xq24-q26. Probes from two loci that identify restriction fragment length polymorphisms (RFLPs) and map to Xq24-q26 showed no recombination with LS. A maximum likelihood recombination distance (theta) = 0.00 was obtained for DXS10 with the logarithm of the odds (lod) of 6.450. For DXS42, theta = 0.00 with a lod of 5.087. Assignment of the gene or genes for LS to Xq24-q26 has the potential of improving carrier detection and providing prenatal diagnosis in families at risk for the disease.
Phase II Trial of CHOP Chemotherapy Followed by Tositumomab/Iodine I-131 Tositumomab for Previously Untreated Follicular Non-Hodgkin's Lymphoma: Five-Year Follow-Up of Southwest Oncology Group Protocol S9911
Authors: Oliver W. Press, Joseph M. Unger, Rita M. Braziel, David G. Maloney, Thomas P. Miller, Michael LeBlanc, Richard I. Fisher
Journal: Journal of Clinical Oncology (2006)

Advanced follicular lymphoma (FL) is incurable with conventional chemotherapy and radiotherapy, and optimal front-line management is controversial. This study was performed to determine the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy followed by tositumomab/iodine I-131 tositumomab.From 1999 to 2000, the Southwest Oncology Group (SWOG) conducted a phase II trial (S9911) to test a novel new regimen consisting of six cycles of CHOP chemotherapy followed 4 to 8 weeks later by tositumomab/iodine I-131 tositumomab in 90 eligible patients with previously untreated, advanced-stage FL.The overall response rate was 91%, including a 69% complete remission (CR) rate. After a median follow-up time of 5.1 years, the estimated 5-year overall survival (OS) rate was 87%, and the progression-free survival (PFS) rate was 67%. The 5-year estimates of OS and PFS were each 23% better (absolute difference) than the corresponding figures for patients treated on previous SWOG protocols with CHOP alone. An analysis according to the Follicular Lymphoma International Prognostic Index showed that 21% of patients had high-risk features, 44% had intermediate-risk features, and 34% had low-risk features. High-risk patients had worse OS than lower risk patients (P = .05), but differences in PFS were not statistically significant (P = .21). Serial monitoring of the t(14;18) translocation in bone marrow by polymerase chain reaction demonstrated that 32 of 38 informative patients obtained molecular CRs, including seven patients (18%) after CHOP and 24 additional patients (63%) after tositumomab/iodine I-131 tositumomab. (The timing of conversion of one patient was unclear.)A prospective, phase III, randomized Intergroup Trial is currently underway comparing the efficacy of the promising CHOP + tositumomab/iodine I-131 tositumomab regimen with the efficacy of CHOP + rituximab.
Mutation in mitochondrial complex I ND6 subunit is associated with defective response to hypoxia in human glioma cells.
Authors: Carrie DeHaan, Bahram Habibi-Nazhad, Elizabeth Yan, Nicole Salloum, Matthew Parliament, Joan Allalunis-Turner
Journal: Molecular Cancer (2004)

Hypoxia-tolerant human glioma cells reduce oxygen consumption rate in response to oxygen deficit, a defense mechanism that contributes to survival under moderately hypoxic conditions. In contrast, hypoxia-sensitive cells lack this ability. As it has been previously shown that hypoxia-tolerant (M006x, M006xLo, M059K) and -sensitive (M010b) glioma cells express differences in mitochondrial function, we investigated whether mitochondrial DNA-encoded mutations are associated with differences in the initial response to oxygen deficit. The mitochondrial genome was sequenced and 23 mtDNA alterations were identified, one of which was an unreported mutation (T-C transition in base pair 14634) in the hypoxia-sensitive cell line, M010b, that resulted in a single amino acid change in the gene encoding the ND6 subunit of NADH:ubiquinone oxidoreductase (Complex I). The T14634C mutation did not abrogate ND6 protein expression, however, M010b cells were more resistant to rotenone, an agent used to screen for Complex I mutations, and adriamycin, an agent activated by redox cycling. The specific function of mtDNA-encoded, membrane-embedded Complex I ND subunits is not known at present. Current models suggest that the transmembrane arm of Complex I may serve as a conformationally driven proton channel. As cellular respiration is regulated, in part, by proton flux, we used homology-based modeling and computational molecular biology to predict the 3D structure of the wild type and mutated ND6 proteins. These models predict that the T14634C mutation alters the structure and orientation of the trans-membrane helices of the ND6 protein. Complex I ND subunits are mutational hot spots in tumor mtDNA. Genetic changes that alter Complex I structure and function may alter a cell's ability to respond to oxygen deficit and consolidate hypoxia rescue mechanisms, and may contribute to resistance to chemotherapeutic agents that require redox cycling for activation.
Decreased Bax expression by mucosal T cells favours resistance to apoptosis in Crohn's disease
Authors: J Itoh
Journal: Gut (2001)

<h3>BACKGROUND</h3> Activated T cells are more susceptible to apoptosis than resting T cells. As intestinal T cells normally exhibit a higher state of activation, increased apoptosis may be necessary to maintain immune homeostasis in the specialised microenvironment of the mucosa. On the other hand, in Crohn9s disease (CD) mucosal T cells are resistant to apoptosis, suggesting abnormal regulation of cell death mechanisms. <h3>AIMS</h3> To investigate differences in expression of anti- and proapoptotic Bcl-2 family proteins, key regulators of apoptosis, between circulating and mucosal T cells, and possible alterations in CD. <h3>PATIENTS AND METHODS</h3> Lamina propria T cells (LPT) were isolated from 10 control, seven CD, and eight ulcerative colitis (UC) patients, and peripheral blood T cells (PBT) from healthy volunteers. Purified T cells were stained intracellularly for Bcl-2, Bcl-x<sub>L</sub>, and Bax, and mean fluorescence intensity measured by flow cytometry. <h3>RESULTS</h3> Compared with PBT, the expression level of Bcl-2 and Bax, but not Bcl-x<sub>L</sub>, was significantly greater in LPT, resulting in lower Bcl-x<sub>L</sub>/Bax ratios. In PBT, Bax expression was highly and significantly correlated with both Bcl-2 and Bcl-x<sub>L</sub>, but correlation with Bcl-2 was absent in LPT. Bax expression in CD, but not UC, LPT was significantly lower than in control LPT, resulting in a significantly higher Bcl-x<sub>L</sub>/Bax ratio. The significant correlation of Bcl-x<sub>L</sub> to Bax was preserved in CD, but not UC, LPT. <h3>CONCLUSIONS</h3> Regulation of Bcl-2 family protein expression differs between circulating and mucosal T cells, probably underlying diverse survival potentials. In CD LPT, a low Bax expression and a high Bcl-x<sub>L</sub>/Bax ratio favour resistance to apoptosis and may contribute to the chronicity of inflammation.
Antigen-like effects of monoclonal antibodies directed at receptors on human T cell clones.
Authors: S C Meuer, J C Hodgdon, R E Hussey, J P Protentis, S F Schlossman, E L Reinherz
Journal: The Journal of Experimental Medicine (1983)

Recent studies suggested that the clonally unique Ti epitopes defined by non-cross-reactive monoclonal antibodies might represent the variable regions of the antigen receptor. Here we determine whether such anti-Ti antibodies could trigger clonal T cell activation. Anticlonotypic monoclonal antibodies to the 49/43-kdalton heterodimer of a given clone or antibodies to the 20/25-kdalton membrane associated monomorphic T3 molecule selectively induce proliferation and IL-2 secretion when linked to a solid support. In contrast, anti-T4 and anti-T8 antibodies under the same conditions have no effect. In conclusion, these results imply that anticlonotypic antibody functions in a fashion analogous to antigen and further support the notion that the T3-Ti molecular complex represents the antigen receptor on human T lymphocytes.
Immunological detection of minimal residual disease in children with acute lymphoblastic leukaemia
Authors: Elaine Coustan-Smith, Frederick G Behm, Joaquin Sanchez, James M Boyett, Michael L Hancock, Susana C Raimondi, Jeffrey E Rubnitz, Gaston K Rivera, J Torrey Sandlund, Ching-Hon Pui, Dario Campana
Journal: The Lancet (1998)
Broad network-based predictability of Saccharomyces cerevisiae gene loss-of-function phenotypes
Authors: Kriston L McGary, Insuk Lee, Edward M Marcotte
Journal: Genome biology (2007)

We demonstrate that loss-of-function yeast phenotypes are predictable by guilt-by-association in functional gene networks. Testing 1,102 loss-of-function phenotypes from genome-wide assays of yeast reveals predictability of diverse phenotypes, spanning cellular morphology, growth, metabolism, and quantitative cell shape features. We apply the method to extend a genome-wide screen by predicting, then verifying, genes whose disruption elongates yeast cells, and to predict human disease genes. To facilitate network-guided screens, a web server is available http://www.yeastnet.org .
The Coincidence of Chromosome 15 Aberrations and β2-Microglobulin Gene Mutations Is Causative for the Total Loss of Human Leukocyte Antigen Class I Expression in Melanoma
Authors: Annette Paschen, Norbert Arens, Antje Sucker, Karin M. Greulich-Bode, Ester Fonsatti, Annunziata Gloghini, Sandra Striegel, Nicole Schwinn, Antonino Carbone, Ralf Hildenbrand, Adelheid Cerwenka, Michele Maio, Dirk Schadendorf
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Total loss of surface presentation of human leukocyte antigen (HLA) class I molecules, protecting tumor cells from the recognition by cytotoxic host CD8+ T cells, is known to be caused by mutations in the β2-microglobulin (β2m) gene. We asked whether abnormalities of chromosome 15, harboring the β2m gene on 15q21, in addition to β2m gene mutations, are causative for the HLA class I–negative phenotype of melanoma cells. Experimental Design: To answer this, we established primary cell lines from the β2m-negative metastatic melanoma tissues of four different patients and analyzed them for β2m gene mutations and chromosome 15 aberrations, the latter by loss of heterozygosity analysis, fluorescence in situ hybridization (FISH), and multicolor FISH. Results: Mutations at the β2m gene level were detected in all cell lines. The loss of heterozygosity analysis of microsatellite markers located on chromosome 15 in three of the four cell lines pointed to an extensive loss of chromosome 15 material. Subsequent molecular cytogenetic analysis revealed the coexistence of apparently normal and rearranged versions of chromosome 15 in three cell lines whereas the fourth cell line solely showed rearranged versions. Two of the four cell lines exhibited a special type of intrachromosomal rearrangement characterized by FISH signals specific for the subtelomeric region of 15q at both ends of the chromosome and one centromeric signal in between. Conclusions: Our data indicate that the complete loss of HLA class I expression in melanoma cells is due to the coincidence of the following mutational events: (a) chromosome 15 instability associated with an extensive loss of genetic material and (b) β2m gene mutations.
The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer.
Authors: P De Camilli, A Thomas, R Cofiell, F Folli, B Lichte, G Piccolo, H M Meinck, M Austoni, G Fassetta, G Bottazzo
Journal: The Journal of Experimental Medicine (1993)

Stiff-Man syndrome (SMS) is a rare disease of the central nervous system (CNS) characterized by progressive rigidity of the body musculature with superimposed painful spasms. An autoimmune origin of the disease has been proposed. In a caseload of more than 100 SMS patients, 60% were found positive for autoantibodies directed against the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). Few patients, all women affected by breast cancer, were negative for GAD autoantibodies but positive for autoantibodies directed against a 128-kD synaptic protein. We report here that this antigen is amphiphysin. GAD and amphiphysin are nonintrinsic membrane proteins that are concentrated in nerve terminals, where a pool of both proteins is associated with the cytoplasmic surface of synaptic vesicles. GAD and amphiphysin are the only two known targets of CNS autoimmunity with this distribution. This finding suggests a possible link between autoimmunity directed against cytoplasmic proteins associated with synaptic vesicles and SMS.
Adipokine profile is modulated in subcutaneous adipose tissue by TNF inhibitors in patients with rheumatoid arthritis
Authors: L. Senolt, M. Kuklova, L. A. Cerezo, H. Hulejova, M. Filkova, L. Bosanska, O. Pecha, K. Pavelka, M. Haluzik, J. Vencovsky
Journal: Annals of the Rheumatic Diseases (2011)

A protective effect of obesity showing that increased adiposity protects against radiographic joint damage in patients with rheumatoid arthritis (RA) has been reported.1 2 Recently, adipokines were suggested as a molecular link explaining this paradoxical association.3,–,5 The levels of serum adiponectin and visfatin have been shown to be associated with increased, radiographic joint damage in RA, while leptin is associated with reduced radiographic joint damage.4 5 Therefore, we tested whether tumour necrosis factor α (TNFα) inhibitor therapy, which prevents joint damage in majority of patients with RA, may be associated with a change in the local production of adipokines in subcutaneous adipose tissue (SAT).

SAT samples were obtained from the same abdominal region by aspiration with a bioptic needle in nine patients with RA prior to and 6 months after the treatment with etanercept. Adipose tissue samples were …
The trade-off between frequency of intercourse and sexual partner accumulation may reflect evolutionary adaptations
Authors: Stuart Brody, Caterina Breitenstein
Journal: Behavioral and Brain Sciences (2000)

The adaptive trade-offs between long- and short-term matings may be mediated or at least reflected partially by the trade-offs between the relative reinforcement obtained through a greater frequency of intercourse (typically greater among cohabitants) versus a greater frequency of partner change. The differing correlates of each approach and meshing with the Sexual Strategies Theory of Gangestad &amp; Simpson are discussed.
Altered expressions of cardiac Na/K-ATPase isoforms in copper deficient rats
Authors: W.-h. Huang, C.-C. Lai, Y. Wang, A. Askari, L. M Klevay, A. Askari, T. H Chiu
Journal: Cardiovascular Research (1995)

The aim was to determine if copper deficiency affects the expression of Na/K-ATPase alpha isoforms in the rat heart.Copper deficiency was induced by placing weanling rats on a copper deficient diet for 4-5 weeks. Adult ventricular tissue, isolated ventricular myocytes, and brain stems of the control and deficient rats were compared for Cu, Zn-superoxide dismutase (CuZn-SOD) activity and for protein and mRNA contents of Na/K-ATPase alpha isoforms.In brain stem, where copper deficiency did not alter CuZn-SOD activity, mRNA and protein levels of alpha isoforms also remained unchanged. In ventricular tissue and ventricular myocytes, copper deficiency reduced CuZn-SOD activity, mRNAs of alpha 1 and alpha 2 isoforms, and the alpha 2 isoform protein. The alpha 1 isoform protein of ventricular tissue and its myocytes was marginally reduced by copper deficiency.In the rat ventricular tissue, oxidative stress resulting from copper deficiency (1) enhances the turnover of the more oxidant sensitive alpha 2 isoform to a greater extent than the turnover of the alpha 1 isoform; (2) regulates mRNA levels of alpha 1 and alpha 2 isoforms; and (3) contributes to the cardiomyopathy of copper deficiency.
Developmental disorders of the enteric nervous system
Authors: R P Kapur
Journal: Gut (2000)

Primary developmental disorders of the human enteric nervous system can be grouped into those characterised by an abnormal number of neurones (hyperganglionosis, hypoganglionosis, aganglionosis) versus abnormal differentiation of neurones (biochemical and/or physiological).1 In each case, the clinical presentation may be similar with a predominance of obstructive symptoms. Comprehensive evaluation of such patients usually involves histopathological studies of a rectal biopsy. However, objective criteria necessary to define and diagnose many enteric dysganglionoses are poorly established or impractical to implement. As a consequence, intestinal aganglionosis and some forms of intestinal hyperganglionosis (for example, MEN2B) may be the only developmental disorders of enteric neurodevelopment that are consistently recognised by most paediatric pathologists. Enteric neurones can also be impaired secondarily by constitutive metabolic defects (for example, lysosomal storage disorders) or acquired forms of injury (for example, ischaemia) but only primary enteric dysganglionoses will be considered in this paper.

Congenital intestinal aganglionosis (Hirschsprung disease, HSCR) is characterised by complete absence of ganglion cells in the submucosal and myenteric plexi. Diagnosis is usually established by histological analysis of suction rectal biopsies that sample small amounts of rectal submucosa (fig 1). Although the sensitivity and specificity of this approach are generally high, reliability depends a great deal on the quality of the biopsy, number of sections examined, and experience of the pathologist.2 The normal sparse distribution of submucosal ganglia necessitates correct sampling and evaluation of multiple tissue sections to avoid …