tbuckley/cabot-search huggingface dataset:
Psychopathology in Patients With Degenerative Cerebellar Diseases: A Comparison to Huntington’s Disease
Authors: Iracema Leroi, Elizabeth O'Hearn, Laura Marsh, Constantine G Lyketsos, Adam Rosenblatt, Christopher A Ross, Jason Brandt, Russell L Margolis
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: This study estimated the psychiatric morbidity of patients with degenerative cerebellar diseases. METHOD: The study included a series of 31 patients with degenerative cerebellar diseases, compared with 21 patients with Huntington's disease and 29 neurologically healthy comparison subjects. Comprehensive psychiatric evaluations, including the Structured Clinical Interview for DSM-IV and psychopathology rating scales, were administered. RESULTS: The overall rate of noncognitive psychiatric disorders was 77% in the patients with degenerative cerebellar diseases, nearly identical to that in the patients with Huntington's disease (81%) and about double that seen in the neurologically healthy subjects (41%). There were high rates of all mood disorders in both the degenerative cerebellar diseases group (68%) and the Huntington's disease group (43%); the rate in the degenerative cerebellar diseases group was significantly higher than that in the neurologically healthy subjects (31%). The frequency of personality change in the three groups was striking: change was present in 26% of the degenerative cerebellar diseases patients, 48% of the Huntington's disease patients, and none of the neurologically healthy comparison subjects. A total of 19% of the degenerative cerebellar diseases subjects and 71% of the Huntington's disease subjects met DSM-IV criteria for either cognitive disorder or dementia. CONCLUSIONS: The high rate of psychiatric and cognitive disorders in the patients with degenerative cerebellar diseases suggests that many, if not most, patients with degenerative cerebellar diseases may benefit from psychiatric interventions. These results also support previous findings that the cerebellum may have a role in modulating emotion and cognition.
Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern
Authors: Aurélie Ambrosi, Stina Salomonsson, Håkan Eliasson, Elisabeth Zeffer, Amanda Skog, Vijole Dzikaite, Gunnar Bergman, Eva Fernlund, Joanna Tingström, Elke Theander, Annika Rydberg, Thomas Skogh, Annika Öhman, Ulla Lundström, Mats Mellander, Ola Winqvist, Michael Fored, Anders Ekbom, Lars Alfredsson, Henrik Källberg, Tomas Olsson, Fredrik Gadler, Anders Jonzon, Ingrid Kockum, Sven-Erik Sonesson, Marie Wahren-Herlenius
Journal: Annals of the Rheumatic Diseases (2011)

Objective Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10–20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. Methods The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. Results There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (p&lt;0.05).Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18–24 occurring during January–March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (p&lt;0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. Conclusion This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.
Development of antigen induced colitis in SCID mice reconstituted with spleen derived memory type CD4+ CD45RB+ T cells
Authors: M-N Kweon
Journal: Gut (2002)

Background and aims: Enteric bacterial and/or food antigens may be crucial in the development of colitis but little is known of the exact mechanism of antigen specific reactions in this condition. The aim of this study was to determine whether systemically primed antigen specific CD4<sup>+</sup> T cells containing both CD45RB<sup>high</sup> and CD45RB<sup>low</sup> populations participate as a pathogenic subset that in turn leads to inflammatory reactions selectively in the large intestine. Methods: SCID mice were reconstituted with splenic CD4<sup>+</sup> CD45RB<sup>+</sup> T cells or CD4<sup>+</sup> CD45RB<sup>low</sup> T cells isolated from donor mice systemically primed with ovalbumin (OVA) plus CFA. The reconstituted mice were then fed OVA for several weeks. Results: Reconstitution of SCID mice with OVA primed splenic CD4<sup>+</sup> T cells, containing populations of CD45RB<sup>high</sup> and CD45RB<sup>low</sup>, resulted in the development of colitis by 4–5 weeks following repeated administration of oral OVA. Histopathological study revealed thickened wall, inflammatory cell infiltration, crypt elongation, and loss of goblet cells in the large intestine. The CD4<sup>+</sup> CD45RB<sup>low</sup> population of cells extracted from the affected large intestine secreted high levels of interferon γ (IFN-γ) and tumour necrosis factor α (TNF-α) at the protein and mRNA levels. Administration of neutralising antibodies to TNF-α, but not to IFN-γ, prevented the development of colitis. Furthermore, adoptive transfer with OVA primed splenic CD4<sup>+</sup> CD45RB<sup>low</sup> T cells evoked severe colitis. Conclusions: These results demonstrate that systemically primed activated/memory CD4<sup>+</sup> CD45RB<sup>low</sup> T cells can mediate the development of specific antigen induced colitis in SCID mice, and also that TNF-α is critical in the induction of this type of colitis. Our results contrast with those from studies in some colitis models in which CD45RB<sup>low</sup> T cells appeared to prevent colitis through secretion of immunosuppressive cytokines.
Postnatal disappearance of self-reactive (V beta 6+) cells from the thymus of Mlsa mice. Implications for T cell development and autoimmunity.
Authors: R Schneider, R K Lees, T Pedrazzini, R M Zinkernagel, H Hengartner, H R MacDonald
Journal: The Journal of Experimental Medicine (1989)

The postnatal ontogeny of potentially autoreactive T cells has been studied in a model system where a particular TCR beta chain variable domain (V beta 6) is correlated with reactivity to a minor antigen encoded by the Mlsa locus. Although absent among mature (CD4+ or CD8+) T cells in adult mice expressing Mlsa, brightly staining V beta 6+ cells were readily detectable in the thymus of neonatal animals, reaching a maximum after 4 d and decreasing rapidly thereafter. These V beta 6+ thymocytes were predominantly of the CD4+ phenotype and were localized in the medulla of the developing thymus. Furthermore, the intensity of TCR expression by these CD4+ cells was significantly (twofold) reduced as compared with age-matched Mlsb controls. A rapid disappearance of CD4+V beta 6+ cells (and corresponding decrease in TCR density) could also be observed in the thymus of Mlsb mice that had been injected neonatally with Mlsa spleen cells. Taken together, these results raise the possibility that some autoreactive T cells may persist after birth and that TCR downregulation may occur as a physiological response to tolerogenic signals in vivo.
Community-acquired lung respiratory infections in HIV-infected patients: microbial aetiology and outcome
Authors: Catia Cilloniz, Antoni Torres, Eva Polverino, Albert Gabarrus, Rosanel Amaro, Encarnacion Moreno, Santiago Villegas, Mar Ortega, Josep Mensa, Maria Angeles Marcos, Asuncion Moreno, Jose M. Miro
Journal: European Respiratory Journal (2014)

We describe the aetiology of community-acquired pneumonia (CAP) in HIV-infected patients, risk factors for bacterial or Pneumocystis jirovecii CAP and prognostic factors of 30-day mortality. This was a prospective observational study of 331 consecutive adult CAP cases in HIV-infected patients (January 2007 to July 2012). 128 (39%) patients had CD4 + cell counts &lt;200 per mm 3 and 99 (43%) ha HIV RNA levels &lt;200 copies per mL on antiretroviral therapy. Streptococcus pneumoniae was the most frequent microorganism in the group with CD4 + cell counts ≥200 per mm 3 ; P. jirovecii was the most frequent microorganism in the group with CD4 + cell counts &lt;200 per mm 3 and in patients with HIV RNA ≥200 copies per mL. Predictors of bacterial CAP were: time with symptoms ≤5 days (OR 2.6, 95% CI 1.5–4.4), C-reactive protein level ≥22 mg·dL −1 (OR 4.3, 95% CI 2.3–8.2) and hepatitis C virus co-infection (OR 2.3, 95% CI 1.4–3.9). White blood cell count ≤4×10 12 per L (OR 3.7, 95% CI 1.2–11.5), lactate dehydrogenase (LDH) level ≥598 U·L −1 (OR 12.9, 95% CI 4.2–39.7) and multilobar infiltration (OR 5.8, 95% CI 1.9–19.5) were predictors of P. jirovecii . Overall 30-day mortality was 7%. Appropriate antibiotic treatment (OR 0.1, 95% CI 0.03–0.4), LDH ≥598 U·L −1 (OR 6.2, 95% CI 1.8–21.8) and mechanical ventilation (OR 22.0, 95% CI 6.2–78.6) were the variables independently associated with 30-day mortality. The described predictors may help clinicians to distinguish between bacterial and P. jirovecii pneumonia in patients with suspected or confirmed HIV infection.
The Complete Mitochondrial Genome Sequence of the Spider Habronattus oregonensis Reveals Rearranged and Extremely Truncated tRNAs
Authors: S. E. Masta
Journal: Molecular Biology and Evolution (2004)

We sequenced the entire mitochondrial genome of the jumping spider Habronattus oregonensis of the arachnid order Araneae (Arthropoda: Chelicerata). A number of unusual features distinguish this genome from other chelicerate and arthropod mitochondrial genomes. Most of the transfer RNA (tRNA) gene sequences are greatly reduced in size and cannot be folded into typical cloverleaf-shaped secondary structures. At least nine of the tRNA sequences lack the potential to form TΨC arm stem pairings and instead are inferred to have TV-replacement loops. Furthermore, sequences that could encode the 3′ aminoacyl acceptor stems in at least 10 tRNAs appear to be lacking, because fully paired acceptor stems are not possible and because the downstream sequences instead encode adjacent genes. Hence, these appear to be among the smallest known tRNA genes. We postulate that an RNA editing mechanism must exist to restore the 3′ aminoacyl acceptor stems to allow the tRNAs to function. At least seven tRNAs are rearranged with respect to the chelicerate Limulus polyphemus, although the arrangement of the protein-coding genes is identical. Most mitochondrial protein-coding genes of H. oregonensis have ATN as initiation codons, as commonly found in arthropod mtDNAs, but cytochrome oxidase subunits 2 and 3 genes apparently use TTG as an initiation codon. Finally, many of the gene sequences overlap one another and are truncated. This 14,381-bp genome, the first mitochondrial genome of a spider yet sequenced, is one of the smallest arthropod mitochondrial genomes known. We suggest that posttranscriptional RNA editing can likely maintain function of the tRNAs, while permitting the accumulation of mutations that would otherwise be deleterious. Such mechanisms may have allowed for the minimization of the spider mitochondrial genome.
Will Bleach Decontaminate Needles During Cocaine Binges in Shooting Galleries?
Authors: Samuel R. Friedman
Journal: JAMA (1989)

<h3>To the Editor. —</h3> Intravenous drug users (IVDUs) are the second largest group of persons at risk for acquired immunodeficiency syndrome in the United States and Europe, and are the major source of heterosexually transmitted acquired immunodeficiency syndrome in the United States and Europe.<sup>1</sup>Many risk-reduction campaigns in the United States emphasize getting IVDUs to use bleach to decontaminate injection equipment. As a result, bleach has become widely used among IVDUs. In vitro studies show that bleach in a 1:10 dilution with water effectively kills human immunodeficiency virus<sup>2</sup>and also inactivates human immunodeficiency virus infection in white blood cells.<sup>3,4</sup>The use of bleach to disinfect injection equipment also appears to be relatively safe.<sup>5</sup>No studies have yet demonstrated whether bleach use affects seroprevalence rates among IVDUs or whether persons who inject different drugs might be more or less likely to use bleach consistently. Two studies<sup>6,7</sup>
Noninvasive estimation of the instantaneous first derivative of left ventricular pressure using continuous-wave Doppler echocardiography.
Authors: C Chen, L Rodriguez, J L Guerrero, S Marshall, R A Levine, A E Weyman, J D Thomas
Journal: Circulation (1991)

BACKGROUND The complete continuous-wave Doppler mitral regurgitant velocity curve should allow reconstruction of the ventriculoatrial (VA) pressure gradient from mitral valve closure to opening, including left ventricular (LV) isovolumic contraction, ejection, and isovolumic relaxation. Assuming that the left atrial pressure fluctuation is relatively minor in comparison with the corresponding LV pressure changes during systole, the first derivative of the Doppler-derived VA pressure gradient curve (Doppler dP/dt) might be used to estimate the LV dP/dt curve, previously measurable only at catheterization (catheter dP/dt). METHODS AND RESULTS This hypothesis was examined in an in vivo mitral regurgitant model during 30 hemodynamic stages in eight dogs. Contractility and relaxation were altered by inotropic stimulation and hypothermia. The Doppler mitral regurgitant velocity spectrum was recorded along with simultaneously acquired micromanometer LV and left atrial pressures. The regurgitant velocity profiles were digitized and converted to VA pressure gradient curves using the simplified Bernoulli equation. The instantaneous dP/dt of the VA pressure gradient curve was then derived. The instantaneous Doppler-derived VA pressure gradients, instantaneous Doppler dP/dt, dP/dtmax, and -dP/dtmax were compared with corresponding catheter measurements. This method of estimating dP/dtmax from the instantaneous dP/dt curve was also compared with a previously proposed Doppler method of estimating dP/dtmax using the Doppler-derived mean rate of LV pressure rise over the time period between velocities of 1 and 3 m/sec on the ascending slope of the Doppler velocity spectrum. Both instantaneous Doppler-derived VA pressure gradients (r = 0.95, p less than 0.0001) and Doppler dP/dt (r = 0.92, p less than 0.0001) correlated well with corresponding measurements by catheter during systolic contraction and isovolumic relaxation (pooled data). The Doppler dP/dtmax (1,266 +/- 701 mm Hg/sec) also correlated well (r = 0.94) with the catheter dP/dtmax (1,200 +/- 573 mm Hg/sec). There was no difference between the two methods for measurement of dP/dtmax (p = NS). Although Doppler -dP/dtmax was slightly lower than the catheter measurement (961 +/- 511 versus 1,057 +/- 540 mm Hg/sec, p less than 0.01), the correlation between measurements by Doppler and catheter was excellent (r = 0.93, p less than 0.0001). The alternative method of mean isovolumic pressure rise (896 +/- 465 mm Hg/sec) underestimated the catheter dP/dtmax (1,200 +/- 573 mm Hg/sec) significantly (on average, 25%; p less than 0.001). CONCLUSIONS The present study demonstrated an accurate and reliable noninvasive Doppler method for estimating instantaneous LV dP/dt, dP/dtmax, and -dP/dtmax.
Abstract 845: Heparin-like polysaccharides reduce osteolytic bone destruction and tumor growth in a mouse model of breast cancer bone metastasis
Authors: Sirkku Pollari, Rami Käkönen, Khalid S. Mohammad, Jukka P. Rissanen, Jussi Halleen, Anni Wärri, Liisa Nissinen, Marjo Pihlavisto, Anne Marjamäki, Merja Perälä, Theresa Guise, Olli Kallioniemi, Sanna-Maria Käkönen
Journal: Cancer Research (2011)

Abstract Transforming growth factor β (TGF-β) is a key regulator of several steps in cancer metastasis, including the establishment of bone metastatic lesions. TGF-β is released from bone during osteoclastic bone resorption and it stimulates breast cancer cells to produce osteolytic factors such as interleukin 11 (IL-11). We conducted a cell-based siRNA screen and identified heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) as a critical gene for TGF-β-induced IL-11 production in highly bone metastatic MDA-MB-231(SA) breast cancer cells. HS6ST2 attaches sulfate groups to glucosamine residues in heparin sulfate which is a member of the glycosaminoglycan family of carbohydrates. Our subsequent studies with highly sulfated heparin-like glycosaminoglycans (HLGAGs) with low anti-coagulant activity indicated that a high-molecular-weight E. coli K5-derived heparin-like polysaccharide (K5-NSOS) inhibited TGF-β-induced IL-11 production in MDA-MB-231(SA) cells. We then evaluated the therapeutic potential of K5-NSOS and a low-molecular-weight synthetic heparin (fragmin) in a mouse model of breast cancer bone metastasis. MDA-MB-231(SA) cells were inoculated into the left cardiac ventricle of athymic nude mice which were then administered with K5-NSOS, fragmin, or vehicle once daily for 4 weeks. Both HLGAGs increased body weight, decreased osteolytic lesion area, and reduced tumor burden in bone. Our in vitro studies showed that both K5-NSOS and fragmin inhibited adhesion of breast cancer cells to ICAM-1, and K5-NSOS also inhibited adhesion to E- and P-selectin. Furthermore, K5-NSOS inhibited bone resorption activity of human osteoclasts in vitro. Our data support and further clarify the critical role of heparan sulfate glycosaminoglycans in breast cancer metastasis and indicate that K5-NSOS is a potential antimetastatic and antiresorptive agent with low anticoagulant activity that could be further optimized as an anti-tumor agent. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 845. doi:10.1158/1538-7445.AM2011-845
A histological study of human wrinkle structures: comparison between sun-exposed areas of the face, with or without wrinkles, and sun-protected areas
Authors: None Contet-Audonneau, None Jeanmaire, None Pauly
Journal: British Journal of Dermatology (1999)

Wrinkles are a major topic in dermocosmetology; the purpose of this work has been to go deeper into the knowledge of cutaneous damage underlying these modifications of skin surface. Up to now, the number of published works about the histological structure of wrinkles is not very large. Therefore to complete the findings, we studied 46 subjects of both sexes, between 57 and 98-year-old, enabling us to obtain 157 skin biopsies of wrinkles (face) and sun-protected areas (abdomen). We used different histological techniques involving histochemistry, immunohistochemistry, electron microscopy and quantification by image analysis in addition to classic standard techniques. This study has allowed us to confirm published structural modifications of wrinkles, but also to display many other original alterations. The increased thinning of the epidermis atrophied with age is confirmed by the study of desmoplakins outlining the cellular contours of keratinocytes. Such a thinning is accompanied by a decrease in several markers of epidermal differentiation at the bottom of the wrinkles: filaggrin, keratohyalin granules and transglutaminase I, disturbing desquamation and the capacity of the horny layer to retain water. The dermoepidermal junction is modified by a decrease of collagen IV and VII, which, combined with fewer and fewer oxytalan fibres under wrinkles, weakens this interface. The deposition of abnormal elastotic tissue in the dermis, with an interruption of these deposits under wrinkles and an atrophy of dermal collagen more pronounced under wrinkles, boosts the magnitude and depth of wrinkles. The composition of the other dermal constituents is also altered with, more particularly, a marked decrease of chondroitin sulphates in the papillary dermis under wrinkles, combined with an asymmetrical variation of glycosaminoglycans on both edges of wrinkles. The atrophy of the hypodermis, also more marked under wrinkles, with a thickening of fibrous lines, also makes the depth of wrinkles more pronounced. Wrinkle formation appears at the same time as numerous modifications in different cutaneous structures, which may be mutually amplified. Such a study by pointing out altered elements in skin physiology, makes the development of specific treatments possible in order to mitigate this unwelcome cutaneous deterioration.
Expression of Basal and Luminal Epithelium-Specific Keratins in Normal, Benign, and Malignant Breast Tissue1
Authors: S. H. Dairkee, L. Puett, A. J. Hackett
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Expression of Basal and Luminal Epithelium-Specific Keratins in Normal, Benign, and Malignant Breast Tissue1 Get access Shahnaz Hashmi Dairkee, Shahnaz Hashmi Dairkee Search for other works by this author on: Oxford Academic PubMed Google Scholar Lynn Puett, Lynn Puett Search for other works by this author on: Oxford Academic PubMed Google Scholar Adeline J. Hackett Adeline J. Hackett 2Peralta Cancer Research Institute3023 Summit St., Oakland, CA 94609 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 9, 6 July 1988, Pages 691–695, https://doi.org/10.1093/jnci/80.9.691 Published: 06 July 1988 Article history Received: 01 February 1988 Revision received: 04 April 1988 Accepted: 12 April 1988 Published: 06 July 1988
Role of cardiac, pulmonary, and carotid mechanoreceptors in the control of hind-limb and renal circulation in dogs.
Authors: G Mancia, J T Shepherd, D E Donald
Journal: Circulation Research (1975)

Reflex control of hind-limb and renal resistance vessels by cardiac and pulmonary receptors was studied by interrupting afferent vagal nerve traffic when only the heart or only the lungs were in situ in anesthetized dogs with sinoaortic denervation. During normocapnia, interruption of cardiac and of pulmonary vagal traffic decreased hind-limb blood flow (constant-pressure perfusion) by 23% and 21%, respectively. Corresponding decreases in renal blood flow were 23% and 33%. Hypercapnia augmented the decreases in renal blood flow due to the vagal block. Thus, the inhibitions exerted by the heart and lung receptores on these two beds were similar during normocapnia but were greater on the renal vessels during hypercapnia. In closed-chest dogs with their aortic nerves sectioned and their carotid sinus pressure controlled, combined withdrawal of carotid and cardiopulmonary inhibition decreased hind-limb and renal blood flow by about 80% and 40%, respectively, during both normovolemia and hypervolemia. Interruption of cardiopulmonary inhibition was responsible for 17% and 31% of the decrease in hind-limb blood flow at normal and increased blood volumes, respectively; values for the decreases in renal blood flow were 50% and 65%. Thus, cardiopulmonary receptors oppose the vasoconstriction due to carotid hypotension more effectively in the kidney than they do in the hind limb.