tbuckley/cabot-search huggingface dataset:
IMMUNE RESPONSES IN VITRO
Authors: Carl W. Pierce, Susan M. Solliday, Richard Asofsky
Journal: The Journal of Experimental Medicine (1972)

The suppressive effects of monospecific goat anti-mouse globulins on primary immunoglobulin class-specific plaque-forming cell responses in mouse spleen cell cultures were investigated. Anti-micro suppressed responses in all immunoglobulin classes, whereas anti-gamma(1) and anti-gamma(2) suppressed the gamma(1) and gamma(2) responses but not gammaM or gammaA responses, and anti-gammaA suppressed only gammaA responses. The mechanism of action of the anti-micro was studied in detail because of its suppression of responses in all immunoglobulin classes. The anti-micro was specific for micro-chain determinants; its activity was dose dependent, but was not mediated by killing cells with surface micro-chain determinants. Free gammaM but not gammaG myeloma proteins in solution effectively competed with micro-bearing cells for the anti-micro. An excess of anti-micro was necessary in the cultures for 48 hr to insure complete suppression of 5-day responses. However, after removal of excess anti-micro at 48 hr, responses could be stimulated by newly added antigen in cultures where incubation was prolonged to 7 days. Anti-micro was most effective when added at the initiation of cultures and had no suppressive effect when added at 48 hr. Excess antigen did not effectively compete with anti-micro for antigen receptors. Precursors of antibody-forming cells were shown to be the cell population where the suppressive activity of anti-micro was mediated. The experiments suggest that anti-micro combines with micro-chain determinants in antigen-specific receptors on the surfaces of antibody-forming cell precursors, prevents effective stimulation by antigen and subsequent antibody production. To explain suppression of responses in all Ig classes by anti-micro, several models were proposed. It is not possible to determine from the data whether stimulation of precursor cells with gammaG or gammaA receptors requires concommitant stimulation of separate cells with only gammaM receptors, or whether cells bearing gammaM receptors are precommitted to or differentiate into cells capable of synthesis of other Ig classes, or whether receptors of gammaM and another Ig class are present on some virgin precursors or the second Ig receptor appears after antigenic stimulation.
Using Pharmacokinetic and Pharmacodynamic Modeling and Simulation to Evaluate Importance of Schedule in Topotecan Therapy for Pediatric Neuroblastoma
Authors: John C. Panetta, Paula Schaiquevich, Victor M. Santana, Clinton F. Stewart
Journal: Clinical Cancer Research (2008)

The study aims to use mathematical modeling and simulation to assess the relative contribution of topotecan systemic exposure and scheduling in the activity and myelosuppression of topotecan in pediatric patients with neuroblastoma.Pharmacokinetic and pharmacodynamic data were obtained from a phase II study for pediatric patients with high-risk neuroblastoma. The topotecan dosage was individualized to attain a topotecan lactone area under the plasma concentration-time curve between 80 and 120 ng/mL h and given over a protracted schedule (i.e., 10 days). Four mathematical models describing topotecan pharmacokinetics, tumor growth, and neutrophil and platelet dynamics were developed. The models were combined to simulate and compare different topotecan treatment strategies with respect to systemic exposure and schedule.The median change in tumor volume was significantly different between schedules (5% increase for D x 5 versus 60% decrease for D x 5 x 2; P < 0.0001) when administering the same total systemic exposure. Whereas protracted schedules showed increased neutropenia (median of 7 versus 12 days below an absolute neutrophil count of 500/microL; P < 0.0001) and thrombocytopenia (median of 3 versus 10 days below a platelet count of 20,000/microL; P < 0.00001), simulations showed that delays in topotecan therapy would not be required. Simulations showed that an increase in topotecan exposure on the D x 5 schedule by 2.4-fold resulted in a modest decrease in tumor volume (i.e., median percentage change tumor volume of 24% versus 3%).The present mathematical model gave an innovative approach to determining relevant topotecan schedules for possible evaluation in the clinic, which could lead to improved tumor response with minimized toxicities.
The Effect of Species Representation on the Detection of Positive Selection in Primate Gene Data Sets
Authors: Ross M. McBee, Shea A. Rozmiarek, Nicholas R. Meyerson, Paul A. Rowley, Sara L. Sawyer
Journal: Molecular Biology and Evolution (2015)

Over evolutionary time, both host- and virus-encoded genes have been continually selected to modify their interactions with one another. This has resulted in the rapid evolution of the specific codons that govern the physical interactions between host and virus proteins. Virologists have discovered that these evolutionary signatures, acquired in nature, can provide a shortcut in the functional dissection of host-virus interactions in the laboratory. However, the use of evolution studies in this way is complicated by the fact that many nonhuman primate species are endangered, and biomaterials are often difficult to acquire. Here, we assess how the species representation in primate gene data sets affects the detection of positive natural selection. Our results demonstrate how targeted primate sequencing projects could greatly enhance research in immunology, virology, and beyond.
Coexistence of C/EBP alpha, beta, growth-induced proteins and DNA synthesis in hepatocytes during liver regeneration. Implications for maintenance of the differentiated state during liver growth.
Authors: L E Greenbaum, D E Cressman, B A Haber, R Taub
Journal: Journal of Clinical Investigation (1995)

During the period of rapid cell growth which follows a two-thirds partial hepatectomy, the liver is able to compensate for the acute loss of two-thirds of its mass to maintain serum glucose levels and many of its differentiation-specific functions. However certain hepatic transcription factors, C/EBP alpha and beta, which are important for establishment and maintenance of the differentiated state, have been shown to be antagonistic to cellular proliferation. To study the interplay between differentiation and cell growth in the liver regeneration model of hepatocyte proliferation, we characterized the expression of C/EBP alpha and beta transcription factors throughout the temporal course of liver regeneration. As determined by immunoblot, the level of C/EBP alpha decreases more than twofold during the mid to late G1 and S phase (8-24 h after hepatectomy) coordinately with a threefold increase in expression of C/EBP beta. Renormalization of the levels of these proteins occurs after the major proliferative phase. This inverse regulation of C/EBP alpha and beta results in up to a sevenfold increase in the beta / alpha DNA binding ratio between 3 and 24 h after hepatectomy that may have an important impact on target gene regulation. However, total C/EBP binding activity in nuclear extracts remains relatively constant during the 7-d period after hepatectomy. By immunohistochemistry, both C/EBP alpha and beta are expressed in virtually all hepatocyte nuclei throughout the liver during the temporal course of liver regeneration, and there is no exclusion of expression from hepatocytes that are expressing immediate-early gene products or undergoing DNA synthesis. The persistent expression of C/EBP alpha and beta isoforms predicts that C/EBP proteins contribute to the function of hepatocytes during physiologic growth and that significant amounts of these proteins do not inhibit progression of hepatocytes into S phase of the cell cycle.
Testosterone and dominance in men
Authors: Allan Mazur, Alan Booth
Journal: Behavioral and Brain Sciences (1998)

In men, high levels of endogenous testosterone (T) seem to encourage behavior intended to dominate--to enhance one's status over--other people. Sometimes dominant behavior is aggressive, its apparent intent being to inflict harm on another person, but often dominance is expressed nonaggressively. Sometimes dominant behavior takes the form of antisocial behavior, including rebellion against authority and low breaking. Measurement of T at a single point in time, presumably indicative of a man's basal T level, predicts many of these dominant or antisocial behaviors. T not only affects behavior but also responds to it. The act of competing for dominant status affects male T levels in two ways. First, T rises in the face of a challenge, as if it were an anticipatory response to impending competition. Second, after the competition, T rises in winners and declines in losers. Thus, there is a reciprocity between T and dominance behavior, each affecting the other. We contrast a reciprocal model, in which T level is variable, acting as both a cause and effect of behavior, with a basal model, in which T level is assumed to be a persistent trait that influences behavior. An unusual data set on Air Force veterans, in which data were collected four times over a decade, enables us to compare the basal and reciprocal models as explanations for the relationship between T and divorce. We discuss sociological implications of these models.
Aneuploidy Predicts Outcome in Patients with Endometrial Carcinoma and Is Related to Lack of <i>CDH13</i> Hypermethylation
Authors: Yutaka Suehiro, Toshiyuki Okada, Takae Okada, Keiko Anno, Naoko Okayama, Koji Ueno, Mikako Hiura, Mikiko Nakamura, Tomoko Kondo, Atsunori Oga, Shigeto Kawauchi, Kei Hirabayashi, Fumitaka Numa, Takehisa Ito, Toshiaki Saito, Kohsuke Sasaki, Yuji Hinoda
Journal: Clinical Cancer Research (2008)

Many investigators have reported that aneuploidy detected by flow cytometry is a useful prognostic marker in patients with endometrial cancer. Laser scanning cytometry (LSC) is a technology similar to flow cytometry but is more feasible for clinical laboratory use. We evaluated the usefulness of DNA ploidy detected by LSC as a prognostic marker in patients with endometrial cancer and investigated genetic and epigenetic factors related to aneuploidy.Endometrial cancer specimens from 106 patients were evaluated. The methylation status of CDH13, Rassf1, SFRP1, SFRP2, SFRP4, SFRP5, p16, hMLH1, MGMT, APC, ATM, and WIF1 and mutations in the p53 and CDC4 genes were investigated. LSC was carried out to determine DNA ploidy. Fluorescence in situ hybridization was done with chromosome-specific centromeric probes to assess chromosomal instability.Univariate and multivariate analyses revealed that p53 mutation and lack of CDH13 hypermethylation associated positively with aneuploidy. Univariate analysis showed that aneuploidy, chromosomal instability, and lack of CDH13 hypermethylation as well as surgical stage were significantly predictive of death from endometrial cancer. Furthermore, multivariate analysis revealed that stage in combination with either DNA aneuploidy or lack of CDH13 hypermethylation was an independent prognostic factor.These results suggest that analysis of DNA ploidy and methylation status of CDH13 may help predict clinical outcome in patients with endometrial cancer. Prospective randomized trials are needed to confirm the validity of an individualized approach, including determination of tumor ploidy and methylation status of CDH13, to management of endometrial cancer patients.
Phosphorylation of Nucleotide Excision Repair Factor Xeroderma Pigmentosum Group A by Ataxia Telangiectasia Mutated and Rad3-Related–Dependent Checkpoint Pathway Promotes Cell Survival in Response to UV Irradiation
Authors: Xiaoming Wu, Steven M. Shell, Zhengguan Yang, Yue Zou
Journal: Cancer Research (2006)

Abstract DNA damage triggers complex cellular responses in eukaryotic cells, including initiation of DNA repair and activation of cell cycle checkpoints. In addition to inducing cell cycle arrest, checkpoint also has been suggested to modulate a variety of other cellular processes in response to DNA damage. In this study, we present evidence showing that the cellular function of xeroderma pigmentosum group A (XPA), a major nucleotide excision repair (NER) factor, could be modulated by checkpoint kinase ataxia-telangiectasia mutated and Rad3-related (ATR) in response to UV irradiation. We observed the apparent interaction and colocalization of XPA with ATR in response to UV irradiation. We showed that XPA was a substrate for in vitro phosphorylation by phosphatidylinositol-3-kinase–related kinase family kinases whereas in cells XPA was phosphorylated in an ATR-dependent manner and stimulated by UV irradiation. The Ser196 of XPA was identified as a biologically significant residue to be phosphorylated in vivo. The XPA-deficient cells complemented with XPA-S196A mutant, in which Ser196 was substituted with an alanine, displayed significantly higher UV sensitivity compared with the XPA cells complemented with wild-type XPA. Moreover, substitution of Ser196 with aspartic acid for mimicking the phosphorylation of XPA increased the cell survival to UV irradiation. Taken together, our results revealed a potential physical and functional link between NER and the ATR-dependent checkpoint pathway in human cells and suggested that the ATR checkpoint pathway could modulate the cellular activity of NER through phosphorylation of XPA at Ser196 on UV irradiation. (Cancer Res 2006; 66(6): 2997-3005)
<i>Caenorhabditis elegans</i> Muscle
Authors: Guy M. Benian, Henry F. Epstein
Journal: Circulation Research (2011)

The nematode Caenorhabditis elegans has become established as a major experimental organism with applications to many biomedical research areas. The body wall muscle cells are a useful model for the study of human cardiomyocytes and their homologous structures and proteins. The ability to readily identify mutations affecting these proteins and structures in C elegans and to be able to rigorously characterize their genotypes and phenotypes at the cellular and molecular levels permits mechanistic studies of the responsible interactions relevant to the inherited human cardiomyopathies. Future work in C elegans muscle holds great promise in uncovering new mechanisms in the pathogenesis of these cardiac disorders.
Endocrine-like cells in the terminal bronchioles and saccules of human fetal lung: an ultrastructural study.
Authors: J McDougall
Journal: Thorax (1978)

An ultrastructural study of Kulschitsky cells was made on lung tissue from five human fetuses of gestational ages between 18 and 25 weeks. The cells were found to occur with relative frequency throughout the bronchi and bronchioles, as well as in the developing saccules. This report describes in detail the cells of the terminal bronchioles and saccules, where their long cytoplasmic processes weave through the epithelium and come into contact with intercellular spaces and the lumen. The cytoplasmic organelles have an orderly arrangement comparable to secreting cells. Dense core vesicles characterise the cytoplasm but clear vesicles and some with less dense, diffuse cores are also present, and may be seen outside the plasma membrane and in the interstitial spaces. The K-cells are usually colsely associated with capillaries or smooth muscle cells across the basement membrane. In addition, the rare occurrence of a small unmyelinated nerve fibre in the vicinity of a K-cell in a terminal bronchiole raises the possibility that the cells fulfill a type of 'mini receptor' role in addition to their probable vasoactive one. Evidence is given that K-cells divide in human fetal lung.
Factors Influencing the Measurement and the Reproducibility of Aryl Hydrocarbon Hydroxylase Activity in Cultured Human Lymphocytes2
Authors: Hira L. Gurtoo, Jun Minowada, Beverly Paigen, Natalie Bejba Parker, Nancy Thompson Hayner
Journal: JNCI Journal of the National Cancer Institute (1977)

Several factors that could influence the activity of aryl hydrocarbon hydroxylase (AHH) in cultured human lymphocytes were examined in an effort to determine optimal conditions for the measurement and reproducibility of this enzyme activity. The following observations were made: a) Under the culture conditions defined here, optimal AHH activity in cultures in Falcon T-30 flasks occurred after 72 hours of incubation; b) AHH-inducibility ratio was affected by the starting cell density; c) storage of blood for 24 hours resulted in the deterioration of the activity, but storage of purified lymphocytes in RPMI-1640 at room temperature for 24 hours resulted in a minimal loss of the activity; d) DNA determinations performed subsequent to the enzyme assays were more reliable than cell counts for the calculation of specific AHH activity; e) a good correlation existed between AHH activity, cellular DNA content, and blastogenesis measured by [3H]thymidine and [14C]amino acid incorporation when phytohemagglutinin (PHA) or concanavalin A was used as mitogen but not when pokeweed or bacterial lipopolysaccharide was used as mitogen; and f) different lots of fetal calf serum significantly affected AHH activity. When culture conditions were strictly controlled and lymphocytes were cultured in the presence of a mitogen combination (1:100 dilution each of PHA and pokeweed mitogen) and 3-methylcholanthrene was used as the inducer, AHH-inducibility ratio in repeat determinations on the same individual was much less variable than the corresponding basal and induced AHH activities, as well as the degree of mitogenic activation (blastogenesis) measured by the incorporation of [3H]thymidine and [14C]amino acids.
Cancer in Patients With Ataxia-Telangiectasia and in Their Relatives in the Nordic Countries
Authors: J H Olsen, J M Hahnemann, A L Børresen-Dale, K Brøndum-Nielsen, L Hammarström, R Kleinerman, H Kääriäinen, T Lönnqvist, R Sankila, N Seersholm, S Tretli, J Yuen, J D Boice, M Tucker
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Epidemiologic studies of the families of patients with ataxia-telangiectasia (A-T), a recessive genetic neurologic disorder caused by mutation of the ATM gene, suggest that heterozygous carriers of an ATM mutation are at increased risk of cancer. A population-based study of cancer incidence in A-T families with unbiased selection and tracing of relatives would confirm this hypothesis. Methods: We conducted a study in the Nordic countries of 1218 blood relatives of 56 A-T patients from 50 families. The relatives were identified from population registries, and the occurrence of cancer was determined from cancer registry files in each country and compared with national incidence rates. All statistical tests were two-sided. Results: Among the 56 patients with A-T, we observed six cases of cancer (four leukemias and two non-Hodgkin's lymphomas) compared with 0.16 expected, yielding a standardized incidence ratio (SIR) of 37 (95% confidence interval [CI] = 13 to 80). Among the 1218 relatives, 150 cancers were recorded, with 126 expected (SIR = 1.19; 95% CI = 1.01 to 1.40). Invasive breast cancer occurred in 21 female relatives of A-T patients (SIR = 1.54; 95% CI = 0.95 to 2.36), including five of the 50 mothers (all of whom are obligate ATM mutation carriers) (SIR = 7.1; 95% CI = 2.3 to 17). Relatives who were less likely to be carriers of a mutant ATM allele had no increase or only a modest, statistically nonsignificant increase in the risk of breast cancer. There was no evidence of increased risk for cancer at any other site. Conclusions: We confirmed the previously recognized high risk of lymphoma and leukemia in A-T patients. Our data are also consistent with an increased risk of breast cancer among blood relatives of A-T patients. The epidemiologic findings suggest, however, that, even if ATM mutations are responsible for some breast cancer cases, ATM is a relatively weak genetic risk factor for the disease.
Regulation by Chemokines of Circulating Dendritic Cell Precursors, and the Formation of Portal Tract–Associated Lymphoid Tissue, in a Granulomatous Liver Disease
Authors: Hiroyuki Yoneyama, Kenjiro Matsuno, Yanyun Zhang, Masako Murai, Meiji Itakura, Sho Ishikawa, Go Hasegawa, Makoto Naito, Hitoshi Asakura, Kouji Matsushima
Journal: The Journal of Experimental Medicine (2000)

We have studied the recruitment and roles of distinct dendritic cell (DC) precursors from the circulation into Propionibacterium acnes–induced granulomas in mouse liver. During infection, F4/80−B220−CD11c+ DC precursors appeared in the circulation, migrated into the perisinusoidal space, and matured within newly formed granulomas. Recruited DCs later migrated to the portal area to interact with T cells in what we term “portal tract–associated lymphoid tissue” (PALT). Macrophage inflammatory protein 1α attracted blood DC precursors to the sinusoidal granuloma, whereas secondary lymphoid organ chemokine (SLC) attracted mature DCs to the newly identified PALT. Anti-SLC antibody diminished PALT expansion while exacerbating granuloma formation. Therefore, circulating DC precursors can migrate into a solid organ like liver, and participate in the granulomatous reaction in response to specific chemokines.
A Community-Based Diabetes Prevention and Management Education Program in a Rural Village in India
Authors: Padmini Balagopal, N. Kamalamma, Thakor G. Patel, Ranjita Misra
Journal: Diabetes Care (2008)

In this study we evaluated a 7-month community-based nonpharmacological lifestyle intervention to prevent/reduce the risk of developing diabetes and its complications in a resource-poor village in Tamilnadu, India.A total of 703 village inhabitants, comprising adults and youth aged 10-92 years, were provided educational intervention using "trained trainers." Culturally and linguistically appropriate health education messages addressed diet, physical activity, and knowledge improvement. The prevalence of diabetes and the effectiveness of the intervention were assessed using select parameters.The crude prevalences of diabetes and pre-diabetes among adults were 5.1 and 13.5%, respectively, while the prevalence of pre-diabetes in youth aged 10-17 years was 5.1%. Intervention reduced fasting blood glucose levels of pre-diabetic adults by 11%, pre-diabetic youth by 17%, and type 2 diabetic adults by 25%. Improvements in obesity parameters and dietary intake also occurred. A stepwise worsening of parameters progressing from the normoglycemic state to the impaired levels of pre-diabetes and diabetes was observed.This study has charted the increasing prevalence of diabetes and pre-diabetes in rural India. Educational intervention was successful in reducing some of the obesity parameters and improving dietary patterns of individuals with pre-diabetes and diabetes.