tbuckley/cabot-search huggingface dataset:
Initial Misdiagnosis and Outcome After Subarachnoid Hemorrhage
Authors: Robert G. Kowalski
Journal: JAMA (2004)

Mortality and morbidity can be reduced if aneurysmal subarachnoid hemorrhage (SAH) is treated urgently.To determine the association of initial misdiagnosis and outcome after SAH.Inception cohort of 482 SAH patients admitted to a tertiary care urban hospital between August 1996 and August 2001.Misdiagnosis was defined as failure to correctly diagnose SAH at a patient's initial contact with a medical professional. Functional outcome was assessed at 3 and 12 months with the modified Rankin Scale; quality of life (QOL), with the Sickness Impact Profile.Fifty-six patients (12%) were initially misdiagnosed, including 42 of 221 (19%) of those with normal mental status at first contact. Migraine or tension headache (36%) was the most common incorrect diagnosis, and failure to obtain a computed tomography (CT) scan was the most common diagnostic error (73%). Neurologic complications occurred in 22 patients (39%) before they were correctly diagnosed, including 12 patients (21%) who experienced rebleeding. Normal mental status, small SAH volume, and right-sided aneurysm location were independently associated with misdiagnosis. Among patients with normal mental status at first contact, misdiagnosis was associated with worse QOL at 3 months and an increased risk of death or severe disability at 12 months.In this study, misdiagnosis of SAH occurred in 12% of patients and was associated with a smaller hemorrhage and normal mental status. Among individuals who initially present in good condition, misdiagnosis is associated with increased mortality and morbidity. A low threshold for CT scanning of patients with mild symptoms that are suggestive of SAH may reduce the frequency of misdiagnosis.
Inhibition of Rac1 activity by controlled release of NSC23766 from chitosan microspheres effectively ameliorates osteoarthritis development in vivo
Authors: Shouan Zhu, Ping Lu, Huanhuan Liu, Pengfei Chen, Yan Wu, Yanyan Wang, Heng Sun, Xiaolei Zhang, Qingqing Xia, Boon Chin Heng, Yiting Zhou, Hong Wei Ouyang
Journal: Annals of the Rheumatic Diseases (2013)

Background Osteoarthritis (OA) is a degenerative joint disease characterised by cartilage degradation and chondrocyte hypertrophy. A recent study showed that Rac1 promoted expression of MMP13 and chondrocyte hypertrophy within the growth plate. These findings warrant further investigations on the roles of Rac1 in OA development and therapy in animal models. Objective To investigate the role and mechanistic pathway of Rac1 involvement in pathological changes of OA chondrocytes in vitro and OA development in vivo, as well as to develop a strategy of modulating Rac1 activity for OA treatment. Material and methods OA and normal cartilage from human or mice were used for immunohistochemical study and Rac1 activity assay. Chondrocytes treated with IL1β and the untreated control were subjected to the Rac1 activity assay. Chondrocytes transfected with CA-Rac1, DN-Rac1 or GFP were cultured under conditions for inducing calcification. To evaluate the effect of Rac1 in OA development, an OA model was created by anterior cruciate ligament transection in mice. CA-Rac1, DN-Rac1 and GFP lentivirus, or NSC23766, were injected intra-articularly. Joints were subjected to histological analysis. Results It was found that there is aberrant Rac1 activation in human OA cartilage. Rac1 activity could also be elevated by IL1β. Additionally, activated Rac1 promoted expression of MMP13, ADAMTS-5 and COLX by chondrocytes, partially through the β-catenin pathway. Moreover, activation of Rac1 in knee joints by CA-Rac1 lentivirus accelerated OA progression, while inhibition of Rac1 activity by DN-Rac1 lentivirus or Rac1 inhibitor NSC23766 delayed OA development. Therefore, we developed a strategy of controlled release of NSC23766 from chitosan microspheres to OA joints, which effectively protected cartilage from destruction. Conclusions These findings demonstrated that Rac1 activity is implicated in OA development. Also, controlled release of Rac1 inhibitor is a promising strategy for OA treatment.
LOSS OF THE PROPERTIES OF HEMOLYSIN AND PIGMENT FORMATION WITHOUT CHANGE IN IMMUNOLOGICAL SPECIFICITY IN A STRAIN OF STREPTOCOCCUS HAEMOLYTICUS
Authors: Rebecca C. Lancefield
Journal: The Journal of Experimental Medicine (1934)

1. A variant arising in a culture of hemolytic streptococcus was shown to have lost the properties of producing pigment and hemolyzing blood. Despite the loss of these two functions, it had in common with the strain from which it was derived certain other distinguishing biochemical characteristics, as follows: Both attained the same hydrogen ion concentration in dextrose broth; both hydrolyzed sodium hippurate, grew on bile agar, and fermented trehalose but not sorbitol; both failed to reduce methylene blue in milk cultures, and were insusceptible to the action of streptococcus bacteriophage. In addition, the virulence of the variant remained the same as that of the original culture. 2. The antigenic and serological specificity of the variant was identical with the group and type specificity of the original strain (Group B, Type I). These specificities were established by the use of immune sera prepared by immunization of rabbits with each form. The immunological reactions employed were reciprocal agglutination, precipitation, agglutinin and precipitin absorption, and passive mouse protection.
Frequency dependence of compliance as a test for obstruction in the small airways
Authors: Ann J. Woolcock, N. J. Vincent, Peter T. Macklem
Journal: Journal of Clinical Investigation (1969)

We selected five bronchitics and four asthmatics in remission, whose routine lung function tests were not significantly abnormal. Dynamic compliance was measured at different respiratory frequencies and the results compared with those obtained from a normal control group. In all patients compliance was frequency dependent and remained so after the administration of bronchodilator aerosols. Compliance was frequency dependent in only one normal subject, and this was completely reversed by bronchodilators. Because the elastic properties of the patients' lungs were normal, and because pulmonary resistance was normal or only minimally increased, we interpret these results as indicating obstruction in peripheral airways.
Attenuated liver progenitor (oval) cell and fibrogenic responses to the choline deficient, ethionine supplemented diet in the BALB/c inbred strain of mice
Authors: Belinda Knight, Barbara Akhurst, Vance B. Matthews, Richard G. Ruddell, Grant A. Ramm, Lawrence J. Abraham, John K. Olynyk, George C. Yeoh
Journal: Journal of Hepatology (2006)
Experimental Cancer Immunotherapy: Comparison of Tumor Rejection in F344 Rats Given Live Mycobacterium bovis (Strain BCG) and Killed Corynebacterium parvum
Authors: Vilas V. Likhite
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Experimental Cancer Immunotherapy: Comparison of Tumor Rejection in F344 Rats Given Live Mycobacterium bovis (Strain BCG) and Killed Corynebacterium parvum Get access Vilas V. Likhite Vilas V. Likhite Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 5, May 1976, Pages 985–989, https://doi.org/10.1093/jnci/56.5.985 Published: 01 May 1976 Article history Received: 20 June 1975 Accepted: 07 November 1975 Published: 01 May 1976
Bronchioloalveolar Pathologic Subtype and Smoking History Predict Sensitivity to Gefitinib in Advanced Non–Small-Cell Lung Cancer
Authors: Vincent A. Miller, Mark G. Kris, Neelam Shah, Jyoti Patel, Christopher Azzoli, Jorge Gomez, Lee M. Krug, William Pao, Naiyer Rizvi, Barbara Pizzo, Leslie Tyson, Ennapadam Venkatraman, Leah Ben-Porat, Natalie Memoli, Maureen Zakowski, Valerie Rusch, Robert T. Heelan
Journal: Journal of Clinical Oncology (2004)

Gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, induces radiographic regressions and symptomatic improvement in patients with non-small-cell lung cancer (NSCLC). Phase II trials suggested female sex and adenocarcinoma were associated with response. We undertook this analysis to identify additional clinical and pathologic features associated with sensitivity to gefitinib. We reviewed medical records, pathologic material, and imaging studies of all 139 NSCLC patients treated on one of three consecutive studies of gefitinib monotherapy performed at our institution. We identified patients experiencing a major objective response and compared their clinical and pathologic features with the others. Univariate and multivariable analyses were performed on potential predictive features associated with sensitivity to gefitinib. Of 139 patients, 21 (15%; 95% CI, 9% to 21%), experienced a partial radiographic response. Variables identified as significant in univariate analysis included adenocarcinoma versus other NSCLC (19% v 0%; P=.004), adenocarcinoma with bronchioloalveolar features versus other adenocarcinomas (38% v 14%; P<.001), never smoker status versus former/current (36% v 8%; P<.001), and Karnofsky performance status > or =80% versus < or =70% (22% v 8%; P=.03). Multivariable analysis revealed the presence of adenocarcinoma with any bronchioloalveolar features (P=.004) and being a never smoker (P=.006) were independent predictors of response. Our data suggest that individuals in whom gefitinib is efficacious are more likely to have adenocarcinomas of the bronchioloalveolar subtype and to be never smokers. These observations may provide clues to mechanisms determining sensitivity to this agent and suggest that NSCLC has a different biology in patients who never smoked and those with bronchioloalveolar carcinoma.
Expression and Immunotherapeutic Targeting of the SSX Family of Cancer–Testis Antigens in Prostate Cancer
Authors: Heath A. Smith, Robert J. Cronk, Joshua M. Lang, Douglas G. McNeel
Journal: Cancer Research (2011)

Recent U.S. Food and Drug Administration approval of the first immunotherapy for prostate cancer encourages efforts to improve immune targeting of this disease. The synovial sarcoma X chromosome breakpoint (SSX) proteins comprise a set of cancer-testis antigens that are upregulated in MHC class I-deficient germline cells and in various types of advanced cancers with a poor prognosis. Humoral and cell-mediated immune responses to the SSX family member SSX2 can arise spontaneously in prostate cancer patients. Thus, SSX2 and other proteins of the SSX family may offer useful targets for tumor immunotherapy. In this study, we evaluated the expression of SSX family members in prostate cancer cell lines and tumor biopsies to identify which members might be most appropriate for immune targeting. We found that SSX2 was expressed most frequently in prostate cell lines, but that SSX1 and SSX5 were also expressed after treatment with the DNA demethylating agent 5-aza-2'-deoxycytidine. Immunohistochemical analysis of microarrayed tissue biopsies confirmed a differential level of SSX protein expression in human prostate cancers. Notably, SSX expression in patient tumor samples was restricted to metastatic lesions (5/22; 23%) and no expression was detected in primary prostate tumors examined (0/73; P < 0.001). We determined that cross-reactive immune responses to a dominant HLA-A2-specific SSX epitope (p103-111) could be elicited by immunization of A2/DR1 transgenic mice with SSX vaccines. Our findings suggest that multiple SSX family members are expressed in metastatic prostate cancers which are amenable to simultaneous targeting.
Phylogenomic Interrogation of Arachnida Reveals Systemic Conflicts in Phylogenetic Signal
Authors: Prashant P. Sharma, Stefan T. Kaluziak, Alicia R. Pérez-Porro, Vanessa L. González, Gustavo Hormiga, Ward C. Wheeler, Gonzalo Giribet
Journal: Molecular Biology and Evolution (2014)

Chelicerata represents one of the oldest groups of arthropods, with a fossil record extending to the Cambrian, and is sister group to the remaining extant arthropods, the mandibulates. Attempts to resolve the internal phylogeny of chelicerates have achieved little consensus, due to marked discord in both morphological and molecular hypotheses of chelicerate phylogeny. The monophyly of Arachnida, the terrestrial chelicerates, is generally accepted, but has garnered little support from molecular data, which have been limited either in breadth of taxonomic sampling or in depth of sequencing. To address the internal phylogeny of this group, we employed a phylogenomic approach, generating transcriptomic data for 17 species in combination with existing data, including two complete genomes. We analyzed multiple data sets containing up to 1,235,912 sites across 3,644 loci, using alternative approaches to optimization of matrix composition. Here, we show that phylogenetic signal for the monophyly of Arachnida is restricted to the 500 slowest-evolving genes in the data set. Accelerated evolutionary rates in Acariformes, Pseudoscorpiones, and Parasitiformes potentially engender long-branch attraction artifacts, yielding nonmonophyly of Arachnida with increasing support upon incrementing the number of concatenated genes. Mutually exclusive hypotheses are supported by locus groups of variable evolutionary rate, revealing significant conflicts in phylogenetic signal. Analyses of gene-tree discordance indicate marked incongruence in relationships among chelicerate orders, whereas derived relationships are demonstrably robust. Consistently recovered and supported relationships include the monophyly of Chelicerata, Euchelicerata, Tetrapulmonata, and all orders represented by multiple terminals. Relationships supported by subsets of slow-evolving genes include Ricinulei + Solifugae; a clade comprised of Ricinulei, Opiliones, and Solifugae; and a clade comprised of Tetrapulmonata, Scorpiones, and Pseudoscorpiones. We demonstrate that outgroup selection without regard for branch length distribution exacerbates long-branch attraction artifacts and does not mitigate gene-tree discordance, regardless of high gene representation for outgroups that are model organisms. Arachnopulmonata (new name) is proposed for the clade comprising Scorpiones + Tetrapulmonata (previously named Pulmonata).
"Anomalous" THY-1(+) killer cells in allogeneic and F1-anti-parental mixed leukocyte culture. Relation to natural killer cells and allospecific cytotoxic T lymphocytes
Authors: K Karre, JK Seeley, E Eriksson, RC Burton, R Kiessling
Journal: The Journal of Experimental Medicine (1982)

Anomalous killer cells are Thy-1(+) blasts that are cytolytic to the natural killer (NK)-sensitive lymphoma YAC-1, and that can be detected early (day 3-4) in the period preceeding the allospecific cytotoxic T lymphocyte (CTL) response in (CBA x A)F1 {arrow} C57B1 mixed leukocyte culture (MLC). We have investigated the origin and nature of anomalous killing (AK), with special emphasis on its relation to NK-and allospecific CTL-activity. AK was shown to be distinct from the previously described "NK(c)-cells" induced by cultivation in fetal calf serum (FCS)-supplemented medium when these two reactivities were examined in parallel. AK was detected in either FCS- or normal mouse serum (NMS)-supplemented allogeneic MLC, indicating that the response was not dependent on mitogenic or antigenic properties of heterologous serum. In addition to several H-2-incompatible combinations, AK was also observed in an Mls-incompatible (but H-2 compatible) and two F(1)- antiparental MLC responder/stimulator combinations. AK cells showed a similar selectivity pattern to NK cells, as demonstrated in cold target inhibition and direct cytotoxicity assays using variant or interferon-modulated YAC-1 cells with low expression of NK target structures. The AK-cells were NK- 1.2(-/weak). Thy-l.2(+), although they seem to be derived from non-adherent radiosensitive cells which are closely related, if not identical, to NK-cells (NK-1.2(+). Thy-l.2(-/weak)), as they could not be readily induced in responder populations with low NK-activity but normal allospecific CTL potential. Conversely, an in vivo thymectomy protocol or treatment of normal spleen cells with monoclonal anti-Thy-1.2 + C reduced the allospecific CTL response drastically but did not affect the AK response. Anomalous killers were not observed when MLC were prepared with responder as well as stimulator cells devoid of mature T cells. In such a combination, the AK response could be partially restored by the addition of irradiated +/nu (but not nu/nu) responder cells to the cultures. When normal (non-nude) spleen cells were used as responders, induction of AK did not require the presence of T cells in the stimulator population, whereas the removal of adherent and phagocytic cells from stimulators abrogated the response. Taken together, the results suggest that AK represents activation, blast transformation, and surface marker modulation of NK cells induced by alloantigen-stimulated T cells, resulting in Thy-1(+) cytolytic cells with similar properties to those described for NK lines, Although AK cells may be regarded as a more T cell-like NK phenotype, their induction is neither necessary, nor sufficient for generation of specific CTL in MLC.
Viral hepatitis in Colombia: A study of the “hepatitis of the Sierra Nevada de Santa Marta”
Authors: Karin E. Ljunggren, Manuel E. Patarroyo, Ronald Engle, Robert H. Purcell, John L. Gerin
Journal: Hepatology (1985)

The prevalences of hepatitis B virus (HBV), hepatitis delta virus and hepatitis A virus infections were studied in two regions of Colombia. In Bogota, 10 of 53 patients with acute hepatitis were HBsAg positive and three of these were hepatitis D antigen positive. Hepatitis A virus was the major cause of acute hepatitis in this group. In 366 healthy controls from Bogota, 1.6% were HBsAg positive and 7.1% had at least one marker of HBV infection. In northern Colombia, individuals from three villages with outbreaks of the fulminant “hepatitis of the Sierra Nevada de Santa Marta” were tested. The prevalences of HBsAg (1.8 to 23%) and HBV infection (35 to 93%) were generally high and varied from village to village; 60% of the HBsAg carriers in one village were positive for antibody to hepatitis D antigen, and two individuals in the outbreak area had circulating hepatitis D antigen. The findings suggest that HBV and the associated hepatitis delta virus are etiologic factors in the “hepatitis of the Sierra Nevada de Santa Marta”.
Transforming Growth Factor–β Regulates Mammary Carcinoma Cell Survival and Interaction with the Adjacent Microenvironment
Authors: Brian Bierie, Daniel G. Stover, Ty W. Abel, Anna Chytil, Agnieszka E. Gorska, Mary Aakre, Elizabeth Forrester, Li Yang, Kay-Uwe Wagner, Harold L. Moses
Journal: Cancer Research (2008)

Abstract Transforming growth factor (TGF)–β signaling has been associated with early tumor suppression and late tumor progression; however, many of the mechanisms that mediate these processes are not known. Using Cre/LoxP technology, with the whey acidic protein promoter driving transgenic expression of Cre recombinase (WAP-Cre), we have now ablated the type II TGF-β receptor (TβRII) expression specifically within mouse mammary alveolar progenitors. Transgenic expression of the polyoma virus middle T antigen, under control of the mouse mammary tumor virus enhancer/promoter, was used to produce mammary tumors in the absence or presence of Cre (TβRII(fl/fl);PY and TβRII(fl/fl);PY;WC, respectively). The loss of TGF-β signaling significantly decreased tumor latency and increased the rate of pulmonary metastasis. The loss of TGF-β signaling was significantly correlated with increased tumor size and enhanced carcinoma cell survival. In addition, we observed significant differences in stromal fibrovascular abundance and composition accompanied by increased recruitment of F4/80+ cell populations in TβRII(fl/fl);PY;WC mice when compared with TβRII(fl/fl);PY controls. The recruitment of F4/80+ cells correlated with increased expression of known inflammatory genes including Cxcl1, Cxcl5, and Ptgs2 (cyclooxygenase-2). Notably, we also identified an enriched K5+ dNp63+ cell population in primary TβRII(fl/fl);PY;WC tumors and corresponding pulmonary metastases, suggesting that loss of TGF-β signaling in this subset of carcinoma cells can contribute to metastasis. Together, our current results indicate that loss of TGF-β signaling in mammary alveolar progenitors may affect tumor initiation, progression, and metastasis through regulation of both intrinsic cell signaling and adjacent stromal-epithelial interactions in vivo. [Cancer Res 2008;68(6):1809–19]
A Long, Naturally Presented Immunodominant Epitope from NY-ESO-1 Tumor Antigen: Implications for Cancer Vaccine Design
Authors: Lisa M. Ebert, Yu Chih Liu, Craig S. Clements, Neil C. Robson, Heather M. Jackson, Jessica L. Markby, Nektaria Dimopoulos, Bee Shin Tan, Immanuel F. Luescher, Ian D. Davis, Jamie Rossjohn, Jonathan Cebon, Anthony W. Purcell, Weisan Chen
Journal: Cancer Research (2009)

The tumor antigen NY-ESO-1 is a promising cancer vaccine target. We describe here a novel HLA-B7-restricted NY-ESO-1 epitope, encompassing amino acids 60-72 (APRGPHGGAASGL), which is naturally presented by melanoma cells. The tumor epitope bound to HLA-B7 by bulging outward from the peptide-binding cleft. This bulged epitope was not an impediment to T-cell recognition, however, because four of six HLA-B7(+) melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX vaccine generated a potent T-cell response to this determinant. Moreover, the response to this epitope was immunodominant in three of these patients and, unlike the T-cell responses to bulged HLA class I viral epitopes, the responding T cells possessed a remarkably broad TCR repertoire. Interestingly, HLA-B7(+) melanoma patients who did not receive the NY-ESO-1 ISCOMATRIX vaccine rarely generated a spontaneous T-cell response to this cryptic epitope, suggesting a lack of priming of such T cells in the natural anti-NY-ESO-1 response, which may be corrected by vaccination. Together, our results reveal several surprising aspects of antitumor immunity and have implications for cancer vaccine design.
Prospective Randomized Study of Intensity-Modulated Radiotherapy on Salivary Gland Function in Early-Stage Nasopharyngeal Carcinoma Patients
Authors: Michael K.M. Kam, Sing-Fai Leung, Benny Zee, Ricky M.C. Chau, Joyce J.S. Suen, Frankie Mo, Maria Lai, Rosalie Ho, Kin-yin Cheung, Brian K.H. Yu, Samuel K.W. Chiu, Peter H.K. Choi, Peter M.L. Teo, Wing-hong Kwan, Anthony T.C. Chan
Journal: Journal of Clinical Oncology (2007)

Purpose This randomized trial compared the rates of delayed xerostomia between two-dimensional radiation therapy (2DRT) and intensity-modulated radiation therapy (IMRT) in the treatment of early-stage nasopharyngeal carcinoma (NPC). Patients and Methods Between November 2001 and December 2003, 60 patients with T1-2bN0-1M0 NPC were randomly assigned to receive either IMRT or 2DRT. Primary end point was incidence of observer-rated severe xerostomia at 1 year after treatment based on Radiotherapy Oncology Group /European Organisation for the Research and Treatment of Cancer late radiation morbidity scoring criteria. Parallel assessment with patient-reported outcome, stimulated parotid flow rate (SPFR), and stimulated whole saliva flow rate (SWSFR) were also made. Results At 1 year after treatment, patients in IMRT arm had lower incidence of observer-rated severe xerostomia than patients in the 2DRT arm (39.3% v 82.1%; P = .001), parallel with a higher fractional SPFR (0.90 v 0.05; P &lt; .0001), and higher fractional SWSFR (0.41 v 0.20; P = .001). As for patient's subjective feeling, although a trend of improvement in patient-reported outcome was observed after IMRT, recovery was incomplete and there was no significant difference in patient-reported outcome between the two arms. Conclusion IMRT is superior to 2DRT in preserving parotid function and results in less severe delayed xerostomia in the treatment of early-stage NPC. Incomplete improvement in patient's subjective xerostomia with parotid-sparing IMRT reflects the need to enhance protection of other salivary glands.