tbuckley/cabot-search huggingface dataset:
Risk Factors for Invasive Cervical Cancer Among Latinas and Non-Latinas in Los Angeles County&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R K Peters, D Thomas, D G Hagan, T M Mack, B E Henderson
Journal: JNCI Journal of the National Cancer Institute (1986)

A case-control study among white women in Los Angeles County was conducted to investigate etiologic factors that might explain the high rates of invasive cervical cancer among Latinas. Two hundred patients with invasive squamous cell carcinoma of the uterine cervix and matched (age, sex, preferred language, and neighborhood) controls were interviewed, 98 pairs in English and 102 pairs in Spanish. Seven factors were found to contribute independently and significantly (P less than .01) to risk, each after adjustment for the other six: years since last Pap smear, years of education (protective), frequency-years douching, pack-years of smoking, years of barrier contraceptive use (protective), number of sexual partners before age 20, and recognized episodes of genital warts. An eighth variable, interval in years between menarche and first intercourse, was the second variable to enter the stepwise logistic regression analysis but lost its statistical significance when sexual partners before age 20 entered the model. Together, these eight variables accounted for almost 99% of the risk. There were no significant interactions between any of these variables and age, language of interview, or birth in a Latin country. There was no increased risk associated with use of oral contraceptives, either before or after adjustment for the other significant factors. Compared to English-speaking controls, Spanish-speaking controls smoked less, douched less, had fewer sexual partners before 20, and had essentially the same average interval between menarche and first intercourse and the same average number of episodes of genital warts; however, they had had a longer interval since their last Pap smear, fewer years of barrier contraceptive use, and fewer years of education. Education, presumably a correlate of an inadequately measured etiologic risk factor (possibly papillomavirus infection), was responsible for the greatest difference in risk between the Spanish- and English-speaking cases.
THE BIOLOGICAL ACTIVITY OF SOLUBLE ANTIGEN-ANTIBODY COMPLEXES
Authors: Kimishige Ishizaka, Teruko Ishizaka, Dan H. Campbell
Journal: The Journal of Experimental Medicine (1959)

Soluble BSA-anti-BSA complexes, formed in antigen excess, give immediate skin reactions in normal guinea pigs. The mechanism of the reaction is not that of passive or reversed passive anaphylaxis. The complex itself is toxic. Skin activity of the complex depends on its composition. It has become obvious that the complex composed of two antigen molecules and one antibody molecule, (Ag2Ab), does not have the activity, whereas, Ag3Ab2 and more complicated complexes do. The role of complement as well as speculation on the structural changes of antibody-antigen complexes is presented.
Family Study of Girls With Attention Deficit Hyperactivity Disorder
Authors: Stephen V. Faraone, Joseph Biederman, Eric Mick, Sarah Williamson, Timothy Wilens, Thomas Spencer, Wendy Weber, Jennifer Jetton, Ilana Kraus, Jim Pert, Barry Zallen
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Because attention deficit hyperactivity disorder (ADHD) is relatively infrequent among girls, little is known about the causes of ADHD in girls. To help fill this gap in the literature, the authors assessed the familial transmission of ADHD in families ascertained through girls.METHOD: Interviewers who were blind to diagnosis administered structured psychiatric interviews to 140 girls with ADHD and their 417 first-degree relatives and to 122 girls without ADHD and their 369 first-degree relatives.RESULTS: The relatives of the ADHD girls had a significantly higher prevalence of ADHD, according to either the DSM-III-R or DSM-IV definition, than the relatives of the comparison girls. However, this did not differ from the prevalence the authors reported previously for families of boys with ADHD. Like the boys’ families, the relatives of the girl probands also had significantly higher prevalences of antisocial, mood, anxiety, and substance use disorders, although the prevalence of familial antisocial disorders was lower than had been observed in the boys’ families. There was no association between the DSM-IV subtypes of the probands and relatives.CONCLUSIONS: The familial transmission of ADHD and comorbid disorders generalizes to families of girls with ADHD. Neither proband gender nor subtype influences the familial transmission of ADHD.
Enzymatically Modified Nonoxidized Low-Density Lipoprotein Induces Interleukin-8 in Human Endothelial Cells
Authors: Prapat Suriyaphol, Dominic Fenske, Ulrich Zähringer, Shan-Rui Han, Sucharit Bhakdi, Matthias Husmann
Journal: Circulation (2002)

Treatment of low-density lipoprotein (LDL) with a protease and cholesterolesterase transforms the lipoprotein to an entity that resembles lipoprotein particles in atherosclerotic lesions, which have a high content of free cholesterol, reflecting extensive de-esterification in the intima. Because de-esterification would occur beneath the endothelium, we examined the effects of enzymatically modified LDL (E-LDL) on cultured endothelial cells.Incubation of endothelial cells with E-LDL provoked selective accumulation of interleukin (IL)-8 mRNA and production of the cytokine. Chemical analyses and depletion experiments indicated that the effect was caused by the presence of free fatty acids in the altered lipoprotein. Reconstitution studies demonstrated that the oleic and linoleic acids associated with E-LDL are particularly effective IL-8 inducers. The effects of E-LDL on endothelial cells could be abrogated with albumin.IL-8 is required for rolling monocytes to adhere firmly to the endothelium; thus, the findings reveal a link between subendothelial entrapment of LDL, cleavage of cholesterol esters, and monocyte recruitment into the lesion.
Alpha thalassemia changes erythrocyte heterogeneity in sickle cell disease.
Authors: C T Noguchi, G J Dover, G P Rodgers, G R Serjeant, S E Antonarakis, N P Anagnou, D R Higgs, D J Weatherall, A N Schechter
Journal: Journal of Clinical Investigation (1985)

Homozygous alpha-thalassemia has the beneficial effect in sickle cell anemia of reducing the hemolytic severity while changing several other hematological parameters. We examined in detail the cellular basis of some of these hematologic alterations. We find that the broad distribution in erythrocyte density and the large proportion of dense cells associated with sickle cell anemia are both reduced with coexisting alpha-thalassemia. Measurements of glycosylated hemoglobin levels as a function of cell density indicate that the accelerated increase in cell density, beyond normal cell aging, in sickle cell anemia is also reduced with alpha-thalassemia. The patients with homozygous alpha-thalassemia and sickle cell disease have slightly lower levels of hemoglobin F than the nonthalassemic sickle cell patients. Examination of hemoglobin F production revealed that the proportion of hemoglobin F containing reticulocytes remained unchanged, as did the proportion of hemoglobin F in cells containing hemoglobin F (F cells). Preferential survival of F cells occurs in sickle cell anemia, with or without alpha-thalassemia, and the slight difference in hemoglobin F levels appear to reflect differences in numbers of circulating F cells. Thus, in sickle cell disease with coexisting alpha-thalassemia, the change in the erythrocyte density profile, possibly due to inhibition of polymerization-related increases in cell density, explains the hematological improvement.
Role of Low-Complexity Sequences in the Formation of Novel Protein Coding Sequences
Authors: M. Toll-Riera, N. Rado-Trilla, F. Martys, M. M. Alba
Journal: Molecular Biology and Evolution (2011)

Low-complexity sequences are extremely abundant in eukaryotic proteins for reasons that remain unclear. One hypothesis is that they contribute to the formation of novel coding sequences, facilitating the generation of novel protein functions. Here, we test this hypothesis by examining the content of low-complexity sequences in proteins of different age. We show that recently emerged proteins contain more low-complexity sequences than older proteins and that these sequences often form functional domains. These data are consistent with the idea that low-complexity sequences may play a key role in the emergence of novel genes.
Cardiac function and haemodynamics in alcoholic cirrhosis and effects of the transjugular intrahepatic portosystemic stent shunt
Authors: M Huonker, Y O Schumacher, A Ochs, S Sorichter, J Keul, M Rössle
Journal: Gut (1999)

BACKGROUND A portosystemic stent shunt may impair cardiac function and haemodynamics. AIMS To investigate the effects of a transjugular intrahepatic portosystemic shunt (TIPS) on cardiac function and pulmonary and systemic circulation in patients with alcoholic cirrhosis. PATIENTS/METHODS 17 patients with alcoholic cirrhosis and recent variceal bleeding were evaluated by echocardiography and catheterisation of the splanchnic and pulmonary circulation before and after TIPS. The period of catheter measurement was extended to nine hours in nine of the patients. The portal vein was investigated by Doppler ultrasound before and nine hours after TIPS. RESULTS Baseline echocardiography showed the left atrial diameter to be slightly increased and the left ventricular volume to be in the upper normal range. Nine hours after TIPS, the left atrial diameter and left ventricular end diastolic volume were increased (by 6% (p&lt;0.01) and 7% (p&lt;0.01) respectively); end systolic volume had not changed significantly. Invasive measurements showed a sharp increase in right atrial pressure (by 101%; p&lt;0.01), mean pulmonary artery pressure (by 92%; p&lt;0.01), pulmonary capillary wedge pressure (by 111%; p&lt;0.01), and cardiac output (8.1 (1.6) to 11.9 (2.4) l/min; p&lt;0.01). Systemic vascular resistance decreased (824 (242) to 600 (265) dyn·s·cm −5 p&lt;0.01), and total pulmonary resistance increased (140 (58.5) to 188 (69.5) dyn·s·cm −5 ; p&lt;0.05). Total pulmonary resistance (12%; NS), cardiac output (1.4 l/min; p&lt;0.05), and portal vein blood flow (1.4 l/min; p&lt;0.05) remained elevated for nine hours after TIPS in the subgroup. Portoatrial pressure gradient (43%; p&lt;0.05), portohepatic vascular resistance (72%; p&lt;0.05), and systemic vascular resistance (27%; p&lt;0.01) were consistently reduced. CONCLUSIONS The increase in the left atrial diameter, the pulmonary capillary wedge pressure, and total pulmonary resistance observed after the TIPS procedure reflected diastolic dysfunction of the hyperdynamic left ventricle in patients with alcoholic cirrhosis. The haemodynamic effects of the portosystemic stent shunt itself on the splanchnic circulation seem to be mainly responsible for the further decrease in systemic vascular resistance. TIPS may unmask a coexisting preclinical cardiomyopathy in patients with alcoholic cirrhosis and portal hypertension.
Nebulized Ceftazidime and Amikacin in Ventilator-associated Pneumonia Caused by <i>Pseudomonas aeruginosa</i>
Authors: Qin Lu, Jianxin Yang, Zhihai Liu, Claudia Gutierrez, Guy Aymard, Jean-Jacques Rouby
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

In experimental pneumonia, nebulization of antibiotics provides high lung tissue concentrations and rapid bacterial killing.To assess the efficacy and safety of nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa.Forty patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa were included in a randomized comparative phase II trial. Twenty patients infected with susceptible or intermediate strains received nebulized ceftazidime (15 mg·kg(-1)·3 h(-1)) and amikacin (25 mg·kg(-1)·d(-1)). Seventeen patients infected with susceptible strains received intravenous ceftazidime (90 mg·kg(-1)·d(-1), continuous administration) and amikacin (15 mg·kg(-1)·d(-1)). In three patients infected with intermediate strains, amikacin was replaced by ciprofloxacin (400 mg·12 h(-1)).After 8 days of antibiotic administration, aerosol and intravenous groups were similar in terms of successful treatment (70 vs. 55%), treatment failure (15 vs. 30%), and superinfection with other microorganisms (15 vs. 15%). Antibiotic-induced changes in lung aeration, determined by computed tomography, were not different between groups (increase in gas volume, 159 ± 460 vs. 251 ± 583 ml; decrease in tissue volume, -58 [-77, 25] vs. -89 [-139, 5] ml). Acquisition of per-treatment antibiotic resistance was observed exclusively in the intravenous group. In the aerosol group, four patients infected with intermediate strains were successfully treated. Nebulization induced an obstruction of the expiratory filter in three patients. The obstruction caused cardiac arrest in one patient, who fully recovered after brief cardiopulmonary resuscitation.Nebulization and intravenous infusion of ceftazidime and amikacin provide similar efficiency for treating ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Nebulization is efficient against intermediate strains and may prevent per-treatment acquisition of antibiotic resistance.
Activation of Natural Killer T Cells by α-Galactosylceramide Rapidly Induces the Full Maturation of Dendritic Cells In Vivo and Thereby Acts as an Adjuvant for Combined CD4 and CD8 T Cell Immunity to a Coadministered Protein
Authors: Shin-ichiro Fujii, Kanako Shimizu, Caroline Smith, Laura Bonifaz, Ralph M. Steinman
Journal: The Journal of Experimental Medicine (2003)

The maturation of dendritic cells (DCs) allows these antigen-presenting cells to initiate immunity. We pursued this concept in situ by studying the adjuvant action of α-galactosylceramide (αGalCer) in mice. A single i.v. injection of glycolipid induced the full maturation of splenic DCs, beginning within 4 h. Maturation was manifest by marked increases in costimulator and major histocompatibility complex class II expression, interferon (IFN)-γ production, and stimulation of the mixed leukocyte reaction. These changes were not induced directly by αGalCer but required natural killer T (NKT) cells acting independently of the MyD88 adaptor protein. To establish that DC maturation was responsible for the adjuvant role of αGalCer, mice were given αGalCer together with soluble or cell-associated ovalbumin antigen. Th1 type CD4+ and CD8+ T cell responses developed, and the mice became resistant to challenge with ovalbumin-expressing tumor. DCs from mice given ovalbumin plus adjuvant, but not the non-DCs, stimulated ovalbumin-specific proliferative responses and importantly, induced antigen-specific, IFN-γ producing, CD4+ and CD8+ T cells upon transfer into naive animals. In the latter instance, immune priming did not require further exposure to ovalbumin, αGalCer, NKT, or NK cells. Therefore a single dose of αGalCer i.v. rapidly stimulates the full maturation of DCs in situ, and this accounts for the induction of combined Th1 CD4+ and CD8+ T cell immunity to a coadministered protein.
Concerted evolution of exons and introns in the MHC-linked tenascin-X gene of mammals
Authors: A. L. Hughes
Journal: Molecular Biology and Evolution (1999)

Two modes of evolution of repeated domains in proteins have been described: (1) a conservative mode, whereby individual domains are conserved across gene duplication and speciation events, and (2) a concerted mode, whereby repeat domains become homogenized within a gene, presumably by intragenic partial duplication and/or gene conversion. The evolution of repeated EGF-like and fibronection-type-III-like (Fn-III) domains in the vertebrate extracellular matrix proteins tenascin-X (TNX) and tenascin-C (TNC) was studied by comparisons between human and mouse orthologs and between the paralogous TNC and TNX genes. The EGF-like repeats have largely been homogenized within each gene by concerted evolution since the duplication of the two genes but have been conserved since the divergence of rodents and primates. The Fn-III domains of TNC have likewise mainly evolved in a conservative fashion since the divergence of rodents and primates. In contrast, the Fn-III repeats of TNX fall into three distinct categories with regard to mode of evolution: (1) The three C-terminal repeats have been conserved since before duplication of the TNX and TNC genes. (2) Certain other repeats have been homogenized within each gene since gene duplication but have been conserved since the divergence of rodents and primates. (3) Still other repeats have evolved in a concerted fashion in rodent and primate lineages since their divergence. Remarkably, certain introns adjacent to the exons encoding these concertedly evolving Fn-III repeats have themselves evolved in a concerted fashion. This is the first known example of concerted evolution of repeated introns within a protein-coding gene.
A phase II study of concurrent cetuximab–cisplatin and intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma
Authors: B B Y Ma, M K M Kam, S F Leung, E P Hui, A D King, S L Chan, F Mo, H Loong, B K H Yu, A Ahuja, A T C Chan
Journal: Annals of Oncology (2011)
Soluble Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Overexpression in HEK293 Cells Promotes Tumor Growth and Angiogenesis in Athymic Nude Mice
Authors: David H. Ho, Hong Vu, Sharron A. N. Brown, Patrick J. Donohue, Heather N. Hanscom, Jeffrey A. Winkles
Journal: Cancer Research (2004)

Abstract Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily of structurally related cytokines. TWEAK acts on responsive cells via binding to a cell surface receptor named Fn14. Recent studies have demonstrated that TWEAK can stimulate numerous cellular responses including cell proliferation, migration, and proinflammatory molecule production. It has also been reported that TWEAK can stimulate blood vessel formation in the rat cornea angiogenesis assay, but it is presently unknown whether this cytokine could play a role in the pathological angiogenesis associated with human diseases such as cancer, rheumatoid arthritis, and diabetic retinopathy. In the present study we investigated whether TWEAK was expressed in human tumors and whether it could promote tumor growth and angiogenesis in vivo. TWEAK mRNA expression was detected in many tumor types by cDNA array hybridization analysis, and TWEAK protein expression was confirmed in human colon cancer tissue by immunohistochemistry. As an initial approach to address whether TWEAK might act as a tumor angiogenesis factor, we established several human embryonic kidney cell lines that constitutively secrete a soluble TWEAK protein and examined their growth properties in vitro and in vivo. We found that although TWEAK-overexpressing cells do not have a growth advantage in vitro, they form larger and more highly vascularized tumors in athymic mice when compared with control, vector-transfected cells. This result suggests that the TWEAK-Fn14 signaling system may be a potential regulator of human tumorigenesis.
Proteomic Signature Corresponding to the Response to Gefitinib (Iressa, ZD1839), an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma
Authors: Tetsuya Okano, Tadashi Kondo, Kiyonaga Fujii, Toshihide Nishimura, Toshimi Takano, Yuichiro Ohe, Koji Tsuta, Yoshihiro Matsuno, Akihiko Gemma, Harbumi Kato, Shoji Kudoh, Setsuo Hirohashi
Journal: Clinical Cancer Research (2007)

Abstract Purpose: We aimed to identify candidate proteins for tumor markers to predict the response to gefitinib treatment. Experimental Design: We did two-dimensional difference gel electrophoresis to create the protein expression profile of lung adenocarcinoma tissues from patients who showed a different response to gefitinib treatment. We used a support vector machine algorithm to select the proteins that best distinguished 31 responders from 16 nonresponders. The prediction performance of the selected spots was validated by an external sample set, including six responders and eight nonresponders. The results were validated using specific antibodies. Results: We selected nine proteins that distinguish responders from nonresponders. The predictive performance of the nine proteins was validated examining an additional six responders and eight nonresponders, resulting in positive and negative predictive values of 100% (six of six) and 87.5% (seven of eight), respectively. The differential expression of one of the nine proteins, heart-type fatty acid–binding protein, was successfully validated by ELISA. We also identified 12 proteins as a signature to distinguish tumors based on their epidermal growth factor receptor gene mutation status. Conclusions: Study of these proteins may contribute to the development of personalized therapy for lung cancer patients.
Cyclin D1 and CDK4 Activity Contribute to the Undifferentiated Phenotype in Neuroblastoma
Authors: Jan J. Molenaar, Marli E. Ebus, Jan Koster, Peter van Sluis, Carel J.M. van Noesel, Rogier Versteeg, Huib N. Caron
Journal: Cancer Research (2008)

Genomic aberrations of Cyclin D1 (CCND1), CDK4, and CDK6 in neuroblastoma indicate that dysregulation of the G(1) entry checkpoint is an important cell cycle aberration in this pediatric tumor. Here, we report that analysis of Affymetrix expression data of primary neuroblastic tumors shows an extensive overexpression of Cyclin D1, which correlates with histologic subgroups. Immunohistochemical analysis showed overexpression of Cyclin D1 in neuroblasts and low Cyclin D1 expression in all cell types in ganglioneuroma. This suggests an involvement of G(1)-regulating genes in neuronal differentiation processes which we further evaluated using RNA interference against Cyclin D1 and its kinase partners CDK4 and CDK6 in several neuroblastoma cell lines. The Cyclin D1 and CDK4 knockdown resulted in pRb pathway inhibition as shown by an almost complete disappearance of CDK4/CDK6-specific pRb phosphorylation, reduction of E2F transcriptional activity, and a decrease of Cyclin A protein levels. Phenotype analysis showed a significant reduction in cell proliferation, a G(1)-specific cell cycle arrest, and, moreover, an extensive neuronal differentiation. Affymetrix microarray profiling of small interfering RNA-treated cells revealed a shift in expression profile toward a neuronal phenotype. Several new potential downstream players are identified. We conclude that neuroblastoma functionally depend on overexpression of G(1)-regulating genes to maintain their undifferentiated phenotype.