tbuckley/cabot-search huggingface dataset:
HIV Testing and Receipt of Test Results Among Homeless Persons With Serious Mental Illness
Authors: Mayur M. Desai, Robert A. Rosenheck
Journal: American Journal of Psychiatry (2004)

The purpose of this study was to determine the rates and predictors of HIV testing and receipt of results among homeless adults with serious mental illness in the initial 3-month period after contact with a community-based case management program.Baseline and follow-up interview data came from clients (N=5,890) in the Access to Community Care and Effective Services and Supports program, an 18-site, 5-year federally sponsored demonstration designed to evaluate the effect of service system integration on outcomes for homeless persons with serious mental illness.Overall, 38.0% of clients were tested for HIV in the 3 months after program entry; of these, 88.8% returned to receive their test results. Likelihood of being tested was independently associated with having been tested before, more severe psychiatric symptoms and drug problems, level of worry about getting AIDS, younger age, less education, minority status, longer-term homelessness, being sexually assaulted, being arrested, and health services utilization. Among those tested, likelihood of receiving the test results was higher among those with a history of prior testing and return for results, a higher frequency of testing, and more years of education and lower among those with drug abuse problems, outpatient medical service utilization, disability, and sexually transmitted disease. Interaction analyses showed that, for men, greater social support increased the likelihood of both HIV testing and receipt of results, while sexual victimization during follow-up decreased the likelihood that men would return for their HIV results.The majority of homeless clients enrolled in an intensive case management program were not tested for HIV during the 3-month period after program entry. Among those tested, however, nearly 90% reported receiving their results. The findings may enhance the development and targeting of strategies to increase testing and awareness of HIV serostatus among high-risk mentally ill homeless persons.
DD-02 * PHARMACODYNAMIC BIOMARKER ASSESSMENTS IN A PHASE I/II TRIAL OF THE HYPOXIA-ACTIVATED PRODRUG TH-302 AND BEVACIZUMAB IN BEVACIZUMAB-REFRACTORY RECURRENT GLIOBLASTOMA
Authors: D. Cavazos, A. Gruslova, J. Sun, J. R. Floyd, L. Fichtel, S. Tadi, A. Lodi, S. Tiziani, C. P. Hart, C. Eng, A. Brenner
Journal: Neuro-Oncology (2014)

BACKGROUND: Glioblastoma (GBM) remains an incurable malignancy with rapid progression and poor survival. GBM exhibits a hypoxic nature, and treatment with bevacizumab (BEV) may increase intratumoral hypoxia. TH-302 is an investigational prodrug that selectively releases the DNA cross-linker (Br-IPM) under hypoxic conditions. A phase I/II trial (NCT01403610) is evaluating the safety and efficacy of combined TH-302 and BEV treatment in patients with BEV-refractory GBM and investigating pharmacodynamics biomarkers. METHODS: Patients were randomized to TH-302 single dose (575 mg/m2) or placebo, administered one day before surgery, followed by TH-302 (240-670 mg/m2) + BEV treatment until disease progression. Before surgery, pimonidazole (Pimo) was administered to label hypoxia and the excised tumor tissue was processed for immunohistochemistry. Endogenous plasma metabolites and plasma carbonic anhydrase IX (CA-IX) were also assessed. RESULTS: Immunohistochemistry was conducted on 11 resected tumors. A strong correlation and co-localization was observed between Pimo (exogenous hypoxia marker) and CA-IX (endogenous hypoxia marker) expression (r = 0.9, p < 0.001). Plasma CA-IX levels correlated well with tissue CA-IX expression. The hypoxic fraction tended to be higher in patients with a stable disease or partial tumor responses. Patients treated with TH-302 prior to surgery tended to have higher levels of γH2AX positive cells, indicating increased DNA damage, and lower Ki67 (a proliferation marker) compared with patients who received placebo. Patients treated with a single dose of TH-302 prior to surgery with higher levels of γH2AX-positive cells tended to have better outcome. Metabolomic profiles in plasma and in tumor tissue differed with degree of hypoxia. CONCLUSION: The results suggest that CA-IX as a hypoxia marker might be a predictive biomarker for TH-302 and γH2AX a response biomarker for TH-302. Correlative studies show metabolomic profile varies with tumor hypoxia degree, indicating plasma metabolites for further study as potential prognostic or treatment response markers.
Familial dilated cardiomyopathy mutations uncouple troponin I phosphorylation from changes in myofibrillar Ca2+ sensitivity
Authors: Massimiliano Memo, Man-Ching Leung, Douglas G. Ward, Cristobal dos Remedios, Sachio Morimoto, Lianfeng Zhang, Gianina Ravenscroft, Elyshia McNamara, Kristen J. Nowak, Steven B. Marston, Andrew E. Messer
Journal: Cardiovascular Research (2013)

The pure form of familial dilated cardiomyopathy (DCM) is mainly caused by mutations in genes encoding sarcomeric proteins. Previous measurements using recombinant proteins suggested that DCM mutations in thin filament proteins decreased myofibrillar Ca2+ sensitivity, but exceptions were reported. We re-investigated the molecular mechanism of familial DCM using native proteins. We used the quantitative in vitro motility assay and native troponin and tropomyosin to study DCM mutations in troponin I, troponin T, and α-tropomyosin. Four mutations reduced myofilament Ca2+ sensitivity, but one mutation (TPM1 E54K) did not alter Ca2+ sensitivity and another (TPM1 D230N) increased Ca2+ sensitivity. In thin filaments from normal human and mouse heart, protein kinase A (PKA) phosphorylation of troponin I caused a two- to three-fold decrease in myofibrillar Ca2+ sensitivity. However, Ca2+ sensitivity did not change with the level of troponin I phosphorylation in any of the DCM-mutant containing thin filaments (E40K, E54K, and D230N in α-tropomyosin; R141W and ΔK210 in cardiac troponin T; K36Q in cardiac troponin I; G159D in cardiac troponin C, and E361G in cardiac α-actin). This 'uncoupling' was observed with native mutant protein from human and mouse heart and with recombinant mutant protein expressed in baculovirus/Sf9 systems. Uncoupling was independent of the fraction of mutated protein present above 0.55. We conclude that DCM-causing mutations in thin filament proteins abolish the relationship between myofilament Ca2+ sensitivity and troponin I phosphorylation by PKA. We propose that this blunts the response to β-adrenergic stimulation and could be the cause of DCM in the long term.
DETERMINANTS AND PROGNOSTIC VALUE OF BRAIN NATRIURETIC PEPTIDE (BNP) FOR CARDIOVASCULAR EVENTS IN A COHORT OF PATIENTS WITH ATRIAL FIBRILLATION
Authors: Laurent Fauchier, Jeanne Patier, Eric Piver, Jean Christophe Pages, Nicolas Clementy, Edouard Simeon, Christophe Saint Etienne, Dominique Babuty, Anne Brunet Bernard
Journal: Journal of the American College of Cardiology (2014)
Convergence of Mortality Rates among Patients on Antiretroviral Therapy in South Africa and North America
Authors: Agnes Binagwaho, Cameron T. Nutt, Placidie Mugwaneza, Claire M. Wagner, Sabin Nsanzimana
Journal: PLoS Medicine (2014)

51Ministry of Health of Rwanda, Kigali, Rwanda, 2Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States ofAmerica, 3Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America, 4Partners In Health, Boston, Massachusetts, United States ofAmerica, 5HIV and Other Sexually Transmitted Infections Division, Rwanda Biomedical Center, Kigali, Rwanda, 6Center for Global Cancer Medicine, Dana Farber CancerInstitute, Boston, Massachusetts, United States of America
Genetic Analysis of Mammographic Breast Density in Adult Women: Evidence of a Gene Effect
Authors: J. S. Pankow, C. M. Vachon, C. C. Kuni, R. A. King, D. K. Arnett, D. M. Grabrick, S. S. Rich, V. E. Anderson, T. A. Sellers
Journal: JNCI Journal of the National Cancer Institute (1997)

The appearance of the female breast viewed by mammography varies considerably from one individual to another because of underlying differences in the relative proportions of fat, connective tissue, and glandular epithelium that combine to create a characteristic pattern of breast density. An association between mammographic patterns and family history of breast cancer has previously been reported. However, this association has not been found in all studies, and few data are available on possible genetic components contributing to mammographic breast density.Our purpose was to estimate familial correlations and perform complex genetic segregation analyses to test the hypothesis that the transmission of a major gene influences mammographic breast density.As part of a cohort study (initiated in 1944) of families with a history of breast cancer, the probands' female relatives who were older than 40 years were asked to obtain a routine mammogram. The mammograms of 1370 women from 258 independent families were analyzed. The fraction of the breast volume occupied by radiographically dense tissue was estimated visually from video displays of left or right mediolateral oblique views by one radiologist experienced in mammography who had no knowledge of individual relationships to the probands. Data on breast cancer risk factors were obtained through telephone interviews and mailed questionnaires. Unadjusted and adjusted familial correlations in breast density were calculated, and complex genetic segregation analyses were performed.Sister-sister correlations in breast density (unadjusted and adjusted for age and either body mass index, menopausal status, hormone replacement therapy, waist-to-hip ratio, number of live births, alcohol consumption, or cigarette smoking status) were all statistically significant (r = .16-.27; all P<.05 [two-sided]). Estimated mother-daughter correlations were smaller in magnitude (r = .01-.17) and not statistically significant. Segregation analyses indicate that a major autosomal gene influences breast density. The mendelian transmission of a dominant gene provided the best fit to the data; however, hypotheses involving the inheritance of either a recessive gene or a codominant gene could not be ruled out. The mendelian dominant hypothesis, accounting for 29% of the variability in breast density, suggests that approximately 12% of the population would be expected to carry at least one variant allele of this putative gene. Women who inherit the variant allele would have a mean breast density about twice that of the rest of the population.Our preliminary findings suggest that, in this cohort of women at risk of breast cancer, mammographic breast density may be genetically influenced.
Big and Slow: Phylogenetic Estimates of Molecular Evolution in Baleen Whales (Suborder Mysticeti)
Authors: J. A. Jackson, C. S. Baker, M. Vant, D. J. Steel, L. Medrano-Gonzalez, S. R. Palumbi
Journal: Molecular Biology and Evolution (2009)

Baleen whales are the largest animals that have ever lived. To develop an improved estimation of substitution rate for nuclear and mitochondrial DNA for this taxon, we implemented a relaxed-clock phylogenetic approach using three fossil calibration dates: the divergence between odontocetes and mysticetes ∼34 million years ago (Ma), between the balaenids and balaenopterids ∼28 Ma, and the time to most recent common ancestor within the Balaenopteridae ∼12 Ma. We examined seven mitochondrial genomes, a large number of mitochondrial control region sequences (219 haplotypes for 465 bp) and nine nuclear introns representing five species of whales, within which multiple species-specific alleles were sequenced to account for within-species diversity (1–15 for each locus). The total data set represents >1.65 Mbp of mitogenome and nuclear genomic sequence. The estimated substitution rate for the humpback whale control region (3.9%/million years, My) was higher than previous estimates for baleen whales but slow relative to other mammal species with similar generation times (e.g., human–chimp mean rate > 20%/My). The mitogenomic third codon position rate was also slow relative to other mammals (mean estimate 1%/My compared with a mammalian average of 9.8%/My for the cytochrome b gene). The mean nuclear genomic substitution rate (0.05%/My) was substantially slower than average synonymous estimates for other mammals (0.21–0.37%/My across a range of studies). The nuclear and mitogenome rate estimates for baleen whales were thus roughly consistent with an 8- to 10-fold slowing due to a combination of large body size and long generation times. Surprisingly, despite the large data set of nuclear intron sequences, there was only weak and conflicting support for alternate hypotheses about the phylogeny of balaenopterid whales, suggesting that interspecies introgressions or a rapid radiation has obscured species relationships in the nuclear genome.
Anxiety Score As a Risk Factor for Radial Artery Vasospasm During Radial Interventions: A Pilot Study
Authors: Süleyman Ercan, Ahmet Unal, Gokhan Altunbas, Hilal Kaya, Vedat Davutoglu, Murat Yuce, Orhan Ozer
Journal: Journal of the American College of Cardiology (2013)
An Intimate Relationship
Authors: Penelope A. Boyden, Henk E.D.J. ter Keurs
Journal: Circulation Research (2005)

e last offered our ideas on the role of reverse EC coupling in the initiation of arrhythmias in 2001. 1 At that time we emphasized that spurious Ca 2ϩ release or oscillations in Ca 2ϩ levels could serve as possible triggers for arrhythmias.Since then much has been done to confirm this role for intracellular Ca 2ϩ .At that time we did not discuss the role of Ca 2ϩ cycling in the maintenance or conversion of stable tachycardias to VF.However, in consideration of the new data on the role of APD restitution in the initiation of VF (increase in wavebreaks; eg, see Garfinkel et al 2 ), we turn our attention now to the role Ca 2ϩ cycling in the myocyte and its impact on APD restitution relations in the isolated rabbit ventricular cell. 3Goldhaber et al consider the role of Ca 2ϩ using different types of APD restitution protocols to emphasize the dynamic nature of intracellular Ca 2ϩ changes and its subsequent impact on the myocyte APD.In their study APD alternans is coupled to Ca 2ϩ cycling, which in itself is not new since others have observed that APD alternans demonstrates a hystersis and is inhibited with BAPTA-AM buffering. 46][7] In fact there has been a large body of work implying that APD alternans and Ca 2ϩ cycling are intimately linked (eg, see 8,9 ).However caution must be raised because Chudin et al 10 have reported that the dynamics of Ca i are altered even when an AP clamp waveform is used.Although the Chudin data may have little relation to the AP dynamics and Ca 2ϩ cycling of normal ventricular myocytes (such as those used in the study of Goldhaber), they may well contribute to our understanding of the dynamics of Ca i cycling in the highly remodeled myocyte where little or no frequency-dependent APD shortening exists due to remodeled potassium channels (eg, epicardial border zone cells).
Expression of COX-2 in Normal and Pyelonephritic Kidney, Renal Intraepithelial Neoplasia, and Renal Cell Carcinoma
Authors: M. Ugur Mungan, Duygu Gurel, A. Erdem Canda, Burcin Tuna, Kutsal Yorukoglu, Ziya Kirkali
Journal: European Urology (2006)
MORPHOLOGICAL AND PATHOGENIC VARIATIONS IN TREPONEMA PALLIDUM
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1912)

When many cultures of Treponema pallidum, whether obtained from the testicular lesions produced in rabbits or directly from human cases of syphilis, are compared, certain definite differences in morphological character become apparent. The different specimens can be divided into thicker and thinner forms or types, and an average or normal form or type. The last is the common or most frequent variety, but the other two occur with sufficient frequency and retain their characters with such constancy as to constitute distinct varieties. Indeed, two of the varieties—the average and the thinner—occurred in association in a chancre and were separated afterwards in cultures. The gross cultural properties of the three varieties present no points of distinction. The lesions caused in the testicle of the rabbit differ according to the variety inoculated, and consist either of a diffuse or of a nodular orchitis. This is a highly important distinction, and if, in the study of a still larger number of specimens of pallida, it is maintained, it is capable of throwing light on certain important clinical features of the human syphilitic disease. The thinner variety of Treponema pallidum resembles in morphology Treponema microdentium, from which it is unmistakably distinguished by cultural characters. The morphological and pathogenic variations in cultures of the pallidum may constitute racial differences within the species.
Systemic Administration of a Novel Immune-Stimulatory Pseudovirion Suppresses Lung Metastatic Melanoma by Regionally Enhancing IFN-γ Production
Authors: Kotaro Saga, Katsuto Tamai, Takehiko Yamazaki, Yasufumi Kaneda
Journal: Clinical Cancer Research (2012)

Cancer immunotherapy has encountered many difficulties in the face of the expectation to eradicate cancer, and new breakthroughs are required. We have previously shown that UV-inactivated Sendai virus particles (hemagglutinating virus of Japan envelope; HVJ-E) induce immunity against multiple tumor types. In this study, a novel pseudovirion that stimulates more robust antitumor immunity was designed for cancer treatment.First, we found that culturing murine splenocytes with HVJ-E in combination with interleukin (IL)-12 resulted in a remarkable increase in IFN-γ production compared with that observed in splenocytes cultured with IL-12 alone. The synergistic effects of HVJ-E and IL-12 on IFN-γ production were caused by viral F proteins independently of HVJ-E fusion activity and not by hemagglutination from hemagglutinin-neuraminidase (HN) proteins. We next constructed HN-depleted HVJ-E expressing the Fc region of immunoglobulin G (IgG) on the envelope and single-chain IL-12 containing the ZZ domain of protein A to produce an IL-12-conjugated HVJ-E particle without hemagglutinating activity.IL-12-conjugated HVJ-E dramatically enhanced the amount of IFN-γ produced by immune cells. Intratumoral injection of IL-12-conjugated HVJ-E eradicated murine melanomas more effectively than injection of wild-type HVJ-E through increased production of melanoma-specific CTLs. IL-12-conjugated HVJ-E preferentially accumulated in the lungs after systemic administration. When small metastatic melanoma foci were formed in the lungs, systemic administration of IL-12-conjugated HVJ-E significantly reduced the number of metastatic foci by inducing local production of IFN-γ in the lungs and generating large numbers of melanoma-specific CTLs.IL-12-conjugated HVJ-E is a promising tool for the treatment of cancers, including lung metastasis.
Targeting Aurora Kinases for the Treatment of Prostate Cancer
Authors: Edmund Chun Yu Lee, Anna Frolov, Rile Li, Gustavo Ayala, Norman M. Greenberg
Journal: Cancer Research (2006)

Abstract Inappropriate expression of the Aurora kinases can induce aberrant mitosis, centrosome irregularities, and chromosomal instability, which lead to anueploidy and cell transformation. Here, we report that Aurora-A and Aurora-B are highly expressed in primary human and mouse prostate cancers and prostate cancer cell lines. In clinical samples, levels of Aurora-A and Aurora-B were significantly elevated in prostatic intraepithelial neoplasia lesions and prostate tumors when compared with the non-neoplastic samples. Interestingly, expression of Aurora-A in non-neoplastic prostates correlated with seminal vesicle invasion (ρ = 0.275, P = 0.0169) and in prostate tumor with positive surgical margins (ρ = 0.265, P = 0.0161). In addition, nuclear expression of Aurora-B in prostatic intraepithelial neoplasia lesions correlated with clinical staging of the tumor (ρ = −0.4, P = 0.0474) whereas cytoplasmic expression in tumors correlated with seminal vesicle invasion (ρ = 0.282, P = 0.0098). Cell lines and primary tumors derived from the TRAMP model were also found to express high levels of Aurora-A and Aurora-B. When human PC3, LNCaP, and mouse C1A cells were treated with the potent Aurora kinase inhibitor VX680, which attenuates phosphorylation of histone H3, cancer cell survival was reduced. VX680 could further reduce cell viability &amp;gt;2-fold when used in combination with the chemotherapy drug doxorubicin. Our findings support a functional relationship between Aurora kinase expression and prostate cancer and the application of small-molecule inhibitors in therapeutic modalities. (Cancer Res 2006; 66(10): 4996-5002)
In individual T cells one productive alpha rearrangement does not appear to block rearrangement at the second allele.
Authors: V Kumar, J L Urban, L Hood
Journal: The Journal of Experimental Medicine (1989)

The T cell lymphoma line BW5147 has rearranged TCR alpha chain genes segments on both the homologous chromosomes: one is functional (V alpha 1) and the second (V alpha 16.1) is a pseudogene. The extreme 3' position of the V alpha 16.1 gene segment in the V alpha locus allows us to recognize rearrangements of most V alpha gene segments using the V alpha 16 probe as a marker. The absence of the genomic V alpha 16.1 gene fragment in mature thymocytes, antigen-specific T cells, and in more than two-thirds of the peripheral T cells suggests that most T lymphocytes rearrange both alpha loci. It appears that productive alpha chain rearrangement on one allele probably does not block a subsequent rearrangement on the other alpha locus.
Heart-type fatty acid binding protein (H-FABP) and brain natriuretic peptide-fragment (BNP-fragment) in COPD patients with pneumonia
Authors: Gulsara Baimakanova, Sergey Avdeev, Alexander Chuchalin
Journal: European Respiratory Journal (2013)

Background: COPD exacerbations are commonly complicated by pneumonia. The cardiac involvement in these cases may also play an important prognostic role.  Aim: To evaluate the value of cardiac dysfunction biomarkers (H-FABP and BNP-fragment) in COPD patients with pneumonia.  Methods: We studied 61 hospitalized patients with acute exacerbation COPD (64.4±7.9 yrs; FEV1 28.1±12.1% pred.), pneumonia was diagnosed in 26 patients of them. All patients underwent investigation including chest X-ray, blood gases, echocardiography, measurement of serum C-reactive protein (CRP), H-FABP, BNP-fragment.  Results: In patients with pneumonia who died during hospital stay (n=11) levels of H-FABP, BNP-fragment were significantly higher than in survivors (11060.6 [3328, 2-17216, 0] vs 1666,2 [3088,1-5779,4] pg/mL and 2066.5 [575.6-6000.0] vs 497.9 [307.4-1854.8] fmol/mL, respectively, p  Conclusions: Increased levels of H-FABP, BNP-fragment were associated with poor outcome of pneumonia. Inflammatory response reflected cardiac dysfunction in COPD patients with pneumonia.