tbuckley/cabot-search huggingface dataset:
Myelodysplastic syndromes: 2015 Update on diagnosis, risk‐stratification and management
Authors: Guillermo Garcia‐Manero
Journal: American Journal of Hematology (2015)

Disease overview : The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy. Diagnosis : Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry, or molecular genetics is complementary but not diagnostic. Risk‐stratification : Prognosis of patients with MDS can be calculated using a number of scoring systems. In general, all these scoring systems include analysis of peripheral cytopenias, percentage of blasts in the bone marrow, and cytogenetic characteristics. The most commonly used system still is probably the International Prognostic Scoring System (IPSS). IPSS is being replaced by the new revised score IPSS‐R. Risk‐adapted therapy : Therapy is selected based on risk, transfusion needs, percent of bone marrow blasts, and more recently cytogenetic and mutational profiles. Goals of therapy are different in lower risk patients than in higher risk. In lower risk, the goal is to decrease transfusion needs and transformation to higher risk disease or AML, as well as to improve survival. In higher risk, the goal is to prolong survival. Current available therapies include growth factor support, lenalidomide, hypomethylating agents, intensive chemotherapy, and allogeneic stem cell transplantation. The use of lenalidomide has significant clinical activity in patients with lower risk disease, anemia, and a chromosome 5 alteration. 5‐Azacitidine and decitabine have activity in higher risk MDS. 5‐Azacitidine has been shown to improve survival in higher risk MDS. A number of new molecular lesions have been described in MDS that may serve as new therapeutic targets or aid in the selection of currently available agents. Additional supportive care measures may include the use of prophylactic antibiotics and iron chelation. Management of progressive or refractory disease : At the present time there are no approved interventions for patients with progressive or refractory disease particularly after hypomethylating based therapy. Options include participation in a clinical trial or cytarabine based therapy and stem cell transplantation. Am. J. Hematol. 90:832–841, 2015. © 2015 Wiley Periodicals, Inc.
The effect of siRNA on invasion capability of small cell lung cancer
Authors: Tao Chen, Jian An Huang, Chuan Yong Mu, Yuan Zeng Gu
Journal: European Respiratory Journal (2012)

Objective To study the inhibitory effect of CXCR4-targeted small interference RNA on invasion capability of NCI-H446 in vitro.

Methods To design chemical synthesis of CXCR4-specific siRNA based on the target sequence for CXCR4 cDNA with NCI-H446 cells transfected with siRNA. To detect the expression of CXCR4 by RT-PCR and Western Blot. Invasion capability of NCI-H446 cells in vitro was evaluated by transwell chamber model and the proliferation capability was determined by CCK-8 assay.

Results After transfected with CXCR4-siRNA, the expression of CXCR4 mRNA and protein was down-regulated significantly. The invasion capability of cells in vitro decreased compared with the empty liposome group. The penetrating number in CXCR4-siRNA transfected group was 32.3±3.8 VS 62.1±8.2(P<0.001).There was no effect on cell proliferation after transfection of CXCR4 siRNA on NCI-H446 cells.

Conclusion CXCR4 siRNA effectively down-regulated the expression of CXCR4 gene and decreased invasion capability of NCI-H446 cells in vitro.
Myocardial 3-Dimensional Printing for Septal Myectomy Guidance in a Patient With Obstructive Hypertrophic Cardiomyopathy
Authors: Dong Hyun Yang, Joon-Won Kang, Namkug Kim, Jae-Kwan Song, Jae-Won Lee, Tae-Hwan Lim
Journal: Circulation (2015)
Early Precursors of Site-Specific Cancers in College Men and Women&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Alice S. Whittemore, Ralph S. Paffenbarger, Keaven Anderson, Jeffrey E. Lee
Journal: JNCI Journal of the National Cancer Institute (1985)

Physical and social characteristics recorded at college physical examination and reported in subsequent questionnaires to alumni in 1962 or 1966 by 50,000 former students from Harvard University and the University of Pennsylvania were reviewed for their relationship to major site-specific cancer occurrence. The records of 1,359 subjects who died with a major site-specific cancer in a 16- to 50-year follow-up period and of 672 subjects who reported such a cancer by mail questionnaire in 1976 or 1977 were compared with those of 8,084 matched classmates who were known to be alive and free of cancer at the time subjects with cancer had died or had been diagnosed. Cigarette smoking, as reported both in student years and years as alumni, predicted increased risk for cancers of the respiratory tract, pancreas, and bladder. Student coffee consumption was associated with elevated risk for leukemia, but it was unrelated to cancers of the pancreas and bladder. Male students with a record of proteinuria at college physical examination experienced increased risk of kidney cancer, and those with a history of tonsillectomy experienced increased risk of prostate cancer. Students who at college entrance reported occasional vague abdominal pain were at elevated risk for pancreatic and colorectal cancers in later years. Increased body weight during college was associated with increased risks of kidney and bladder cancers, whereas for alumni this index was associated only with kidney cancer. Increased weight-for-height during college (but not in 1962 or 1966) predicted increased occurrence of female breast cancer. Jewish students experienced elevated risk for subsequent cancers of the female breast, colon, and combined colorectum. These and other findings are presented as clues deserving further exploration for any etiologic significance that they may hold for the cancer sites studied.
<i>Ex Vivo</i> Culture of CTCs: An Emerging Resource to Guide Cancer Therapy
Authors: Shyamala Maheswaran, Daniel A. Haber
Journal: Cancer Research (2015)

With increasing application of targeted therapies and the development of acquired resistance, much attention is being focused on developing in vitro and in vivo patient-specific tumor models for individualized therapeutic evaluation of cancers. Circulating tumor cells provide a source of noninvasively and sequentially sampled invasive cancer cells suitable for propagation in vitro. We review the advantages and challenges associated with ex vivo culture of tumor cells circulating in the blood of patients with cancer.
Squamous cell carcinoma antigen: prognostic significance and role in the monitoring of neoadjuvant chemotherapy response in cervical cancer.
Authors: G Scambia, P Benedetti Panici, E Foti, M Amoroso, G Salerno, G Ferrandina, F Battaglia, S Greggi, A De Gaetano, G Puglia
Journal: Journal of Clinical Oncology (1994)

PURPOSE The aim of the study was to investigate the role of squamous cell carcinoma antigen (SCC) in the management of patients with locally advanced cervical cancer treated by neoadjuvant chemotherapy and radical surgery. PATIENTS AND METHODS SCC assay was performed with a radioimmunoassay kit in a series of 102 patients with locally advanced cervical cancer. The values of 2.5, 5, and 7 ng/mL were used to define SCC antigen positivity. The chi 2 and Fisher's exact test and the stepwise logistic regression were used to evaluate the distribution of marker values. Analysis of survival was performed using the Kaplan and Meier test and Cox multivariate regression analysis. RESULTS SCC levels were elevated in 65%, 45%, and 32% of patients with primary tumors for cutoff values of 2.5, 5, and 7 ng/mL, respectively. SCC pretreatment levels correlated with stage, tumor volume and lymph node status. In the multivariate analysis, SCC expression proved to be an independent predictor of response to neoadjuvant chemotherapy. SCC posttreatment levels were strongly related to chemotherapy response. Moreover, the overall correlation between the clinical course of the disease and the variation of SCC levels was 83%. In patients with squamous cell tumors, survival was significantly longer in SCC-negative cases compared with SCC-positive cases (P = .04). Moreover, in patients undergoing surgery after response to neoadjuvant chemotherapy, low SCC values were associated with better prognosis (P = .02). In the multivariate analysis, parametrial involvement and SCC status proved to retain an independent prognostic value. CONCLUSION Our data show that SCC assay may provide useful information to improve the prognostic characterization and disease monitoring of patients with locally advanced cervical cancer undergoing neoadjuvant chemotherapy.
Prime-boost vaccination with chimpanzee adenovirus and modified vaccinia Ankara encoding TRAP provides partial protection against <i>Plasmodium falciparum</i> infection in Kenyan adults
Authors: Caroline Ogwang, Domtila Kimani, Nick J. Edwards, Rachel Roberts, Jedidah Mwacharo, Georgina Bowyer, Carly Bliss, Susanne H. Hodgson, Patricia Njuguna, Nicola K. Viebig, Alfredo Nicosia, Evelyn Gitau, Sandy Douglas, Joe Illingworth, Kevin Marsh, Alison Lawrie, Egeruan B. Imoukhuede, Katie Ewer, Britta C. Urban, Adrian V. S. Hill, Philip Bejon, Odile Leroy, Badara Cisse, Sodiomon Sirima, Kalifa Bojang, Georgina Murphy, Henry Karanja, Lydiah Nyamako, Simone De Cassan, Ken Awuondo, Dominic Kwiatkowski, Kirk Rockett, Sarah Gilbert, Nicholas Anagnostou, Peninah Soipei, Judy Peshu, Ines Petersen, Brian Mutinda, Naomi Waithira, Mahfudh Bashraheil, Jimmy Shangala, Sarah Moyle, Eleanor Berrie, Geoffrey Targett, Mahamadou Thera, Paul Milligan, Bernhards Ogutu, Anthony Etyang
Journal: Science Translational Medicine (2015)

Vaccination with the recombinant viral vectors chimpanzee adenovirus 63 followed by modified vaccinia Ankara both encoding the malaria sequence ME-TRAP conferred 67% protection against infection with Plasmodium falciparum in Kenyan adults.
Progressive Loss of H-2 Antigens With Concomitant Increase of Cell-Surface Antigen(s) Determined by Moloney Leukemia Virus in Cultured Murine Lymphomas23
Authors: Matko Cikes, Sten Friberg, George Klein
Journal: JNCI Journal of the National Cancer Institute (1973)

Two Moloney leukemia virus (MLV)-induced murine lymphomas (YCAB and YAC) and a spontaneous murine lymphoma (WL4) were serially propagated in the ascites form in syngeneic hosts. At intervals, culture lines were established and maintained as stationary suspension cultures for a few days to 3 years. In vitro lines derived from all 3 lymphomas had less H-2 antigens and more MLV-determined cell-surface antigen(s) than the corresponding in vivo lines in syngeneic hosts. This was shown by the sensitivity of the cells to complement-dependent, antibody-mediated cytolysis, indirect membrane immunofluorescence, and quantitative absorption tests. The antigenic changes took place progressively after explantation and were correlated with the number of cell generations in culture. The final cell densities of the culture lines were also correlated with the number of cell generations in culture; e.g., a sevenfold increase in the final cell density was observed in a long-established YCAB culture line, compared with a newly established line of the same tumor.
Testicular Teratomas in Fetal Mice&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: L C Stevens
Journal: JNCI Journal of the National Cancer Institute (1962)

Fifty-nine teratomatous foci from 27 testes of fetal 129/Sv-Sl mice 15 to 19 days of gestation are described. The incidence of tumors in fetuses is the same as in older mice, which demonstrates origin during a prenatal period and not later. Judged by the appearance of these fetal tumors, teratocar-cinogenesis may be initiated shortly before 15 days' gestation, and the period of susceptibility to teratocarcinogenesis may extend to as late as (but not later than) 17 days' gestation. All 24 tumorous foci in testes of 15- and 16-day fetuses were entirely enclosed within intact seminiferous tubules, which demonstrated that they were derived from a component of the seminiferous tubules, probably the primordial germ cell. Seven foci in 16- and 17-day fetuses were completely intratubular, while 14 were larger and had invaded the walls of the tubules in which they originated. Tumor cells migrated into the interstitial area. All four 19-day tumors had intratubular areas continuous with extratubular areas. There was no indication that any extratubular element contributed to the formation of teratomas. Usually tumorous testes had a small number of foci located near each other within the same tubule. These foci appeared to represent clones derived from a primordial germ cell in which neoplastic transformation occurred prior to its establishment in its definitive peripheral position in the tubule. Many foci contained primitive epithelium similar in appearance to embryonic ectoderm. All the varied components of teratomas in older animals, including germ layers and immature and adult tissues, are derived from intratubular tumors in fetuses.
Normal anagen effluvium: a sign of pemphigus vulgaris
Authors: S. Delmonte, M.T. Semino, A. Parodi, A. Rebora
Journal: British Journal of Dermatology (2000)

S ir, The term anagen effluvium usually refers to the dystrophic anagen shedding usually seen in conditions such as alopecia areata or treatment with antimitotic drugs. In those conditions, the hair has peculiar microscopic features, namely a sharpened proximal end, a paler colour and loss of its outer root sheath. A similar pattern of anagen hair shedding is observed in the loose anagen syndrome, a rare congenital childhood disease, 1 in which the hair bulb is misshapen and the outer root sheath is missing. Never have hairs been reported to shed as normal anagen hairs with their intact root sheaths. We describe three patients with pemphigus vulgaris in whom this was the case. Patient 1. A 70‐year‐old woman presented with itching scalp lesions of 1 month duration. Examination showed an erythematous crusted non‐scarring alopecic patch at the vertex. Hairs were easily plucked from perilesional areas and looked like normal anagen hairs with intact root sheaths.
Accuracy of variables describing ethnic minority groups is important
Authors: K. Mckenzie
Journal: BMJ (1995)

schizophrenia is increased for black people and Asians compared with the local white population in Merton and Wandsworth.There seems, however, to be an additional risk for black people living in Wandsworth.There is a non-significant trend to a slightly increased risk of bipolar affective disorder.As a service driven instrument the long term case register does not have the epidemiological robustness of King and colleagues' study, but we do not consider our findings to be artefacts.The differences among ethnic groups have been stable over five years despite a 47% turnover of people on the register and a 70% change in the consultants making the clinical diagnoses.Furthermore, as mental health services are often considered to be inaccessible to ethnic minorities the long term case register may be expected to underestimate the
HER2/neu gene amplification and copy numbers of HER2/neu and chromosome 17 assessed by fluorescence in situ hybridization (FISH) are not predictive of outcome in resected pancreatic cancer
Authors: A. M. Krasinskas, S. Sharif, K. Cieply, D. Potter, B. Elinoff, L. Liao, R. K. Ramanathan
Journal: Journal of Clinical Oncology (2005)

4117 Background: HER2/neu is an oncogene on chromosome (chr) 17 that encodes a type I tyrosine kinase growth factor receptor. In breast cancer, HER2/neu status evaluated by immunohistochemistry (IHC) and FISH is a reliable prognostic indicator of tumor behavior and is used for treatment planning. In pancreatic cancer (PC), HER2/neu protein overexpression has been studied mostly by IHC, but its significance is still unclear. Our objective was to use FISH to correlate various tumor characteristics and patient survival with HER2/neu gene amplification and copy numbers of HER2/neu and chr 17. Methods: HER2/neu gene amplification (defined as a ratio of HER2/neu to chr 17 centromere of >2), HER2/neu copy number (cutoff >5) and chr 17 copy number (cutoff >1.9) were assessed by FISH in 65 surgically resected PC. FISH results were compared to these tumor characteristics: Size, Grade (1=well, 2=moderately, 3=poorly differentiated), TNM stage and patient survival. Statistical analysis was performed using Fisher’s exact test, Wilcoxon test and Kaplan-Meier survival curves. Results: The mean age was 67 and 54% were females. Tumor characteristics: mean tumor size, 3.1cm; median histologic grade, 2 out of 3; Stage T3 N1 (50.8%), followed by T3 N0 (16.9%), T1 N0 (9.2%), T1 N1, T2 N0 (6.2% each), T2 N1, T4 N1 (4.6% each) and T4 N0 (1.5%). HER2/neu gene amplification was detected in 16/65 (25%) tumors. The average HER2/neu and chr 17 copy numbers were 3.20 and 1.67, respectively. When HER2/neu gene amplification and copy numbers of HER2/neu and chr 17 were correlated with tumor size, grade, T and N stage, and overall survival, no statistical significance was found. Conclusions: Sixteen out of 65 (25%) PCs demonstrated HER2/neu gene amplification. No association was found with tumor size, grade, T and N stage or overall survival. HER2/neu and chr 17 copy numbers are not markers of aggressive disease in PC. These observations suggest that HER2/neu amplification does not play an important role in the progression of PC as it does in breast cancer. Whether agents such as trastuzumab (Herceptin) will be effective in PC remains to be determined in clinical trials. No significant financial relationships to disclose.
Dementia with a Prosthetic Aortic Valve
Authors: D Dutta, C E Ashton
Journal: Journal of the Royal Society of Medicine (2001)

To reduce the incidence of thromboembolism, a cloth-covered version of the Starr—Edwards aortic valve was introduced in 1968 (Figure 1)1. A new complication then arose—systemic embolism due to cloth tears1,2,3.



Figure 1

Cloth-covered Starr-Edwards model 2310/2320 aortic prosthesis used from 1968 to 1975. Reproduced from Ref. 1 by permission
LSC 2014 abstract - Combined effects of inflammatory mediators and BMPR2 mutation on pulmonary arterial cell function in a pulmonary arterial hypertension
Authors: Leanda Vengethasamy, Rozenn Quarck, Marion Delcroix
Journal: European Respiratory Journal (2014)

Mutations in  bone morphogenetic protein receptor  ( BMPR2 ) gene have been observed in 70% of patients with heritable pulmonary arterial hypertension (HPAH) and in 11-40% with idiopathic PAH (IPAH). All patients with  BMPR2  mutation do not develop PAH suggesting a second hit, such as inflammation, could be involved in the pathogenesis of PAH. Our aim was to determine if inflammation, in addition to impaired BMPR2 signaling, could contribute to pulmonary arterial cell dysfunction in PAH. Pre-capillary pulmonary arterial endothelial (EC) and smooth muscle cells (SMC) were isolated from lung parenchyma of transplanted patients with IPAH (n=2) and HPAH with a  BMPR2  mutation (n=1).Adhesion capacities of CRP- and TNFα-activated EC to human monocytic cells (U937) and effects of CRP and EC on SMC mitogenic activity were assessed. Intercellular adhesion molecule-1 ( ICAM-1 ) expression was analyzed in human lung microvascular EC ( HLMVEC ) in response to activated U937 cells. CRP and TNFα increased adhesion of EC to U937 by 105% and 249% (IPAH) and 227% and 635% (HPAH), respectively. CRP increased SMC mitogenic activity by 1.4-fold (IPAH) and 2.2-fold (HPAH)  vs.  control (0.2% FBS). Presence of resting pre-capillary EC increased SMC mitogenic activity by 2.6% (IPAH) and 8.6% (HPAH). Activated U937 cells induced increased ICAM-1 expression at HLMVEC surface. These results show that pre-capillary pulmonary EC and SMC from HPAH patient have enhanced adhesion capacities and mitogenic activity in the presence of inflammatory mediators and potential cross-talk between EC and SMC.Inflammation may contribute to pulmonary arterial cell dysfunction in PAH.
The histone-deacetylase-8 selective inhibitor PCI-34051 enhances IFN-λ production in vitro and reduces inflammation in mouse models of rhinoviral infection and rhinovirus-induced exacerbations of asthma in vivo
Authors: Martina Bosnar, Gabrijela Ergovic, Boska Hrvacic, Kosjenka Frka Boric, Andrea Paravic Radicevic, Ines Glojnaric, Vesna Erakovic Haber
Journal: European Respiratory Journal (2013)

An impaired immune response to viral infection, in particular reduced production of type I and III interferons (IFN), is considered to be an important mechanism of greater susceptibility of asthmatic patients to respiratory infections. Therefore, novel therapies aimed at replacing or augmenting deficient IFN production are being investigated.  According to the literature, histone-deacetylase-8 (HDAC8) is a negative regulator of innate antiviral responses since it functions as a repressor for IFN-β gene expression. Consequently, HDAC8 silencing increases IFN-β mRNA levels.  The aim of this work was to validate HDAC8 as a pharmacological target by using PCI-34051, HDAC8 selective inhibitor, as a tool compound.  We have shown that PCI-34051, HDAC8 selective inhibitor (IC 50  10nM) with >200-fold selectivity over the other HDAC isoforms, enhanced IFN-λ production in human bronchial cells from normal and asthmatic donors after rhinovirus (RV1B and RV16) infection.  In vivo , PCI-34051 reduced cell counts in bronchoalveolar lavage fluid (BALF) and viral load in lung tissue of mice infected with RV-1B. Finally, the compound was also effective at reducing BALF cell counts and cytokine concentration in a mouse model of rhinovirus-induced exacerbation of allergic airway inflammation. Taken together, these findings indicate that inhaled selective HDAC8 inhibitors could be useful as a novel treatment for rhinovirus-induced exacerbations of asthma.
Posttraumatic stress disorder and concurrent psychiatric illness: a preliminary report
Authors: F S Sierles, J J Chen, R E McFarland, M A Taylor
Journal: American Journal of Psychiatry (1983)

Twenty-five combat veterans hospitalized for treatment of posttraumatic stress disorder were evaluated for the presence of other disorders. Fourteen patients (56%) met operationally defined criteria for one additional diagnosis, five (20%) for two additional diagnoses, and two (8%) for three additional diagnoses. The coexisting syndromes included alcoholism, drug dependence, antisocial personality disorder, somatization disorder, endogenous depression, and organic mental syndrome. The authors caution that neither the stress disorder nor the coexisting syndrome should be considered the primary condition; clinicians should screen patients with stress disorders for other conditions and treat them when possible.