tbuckley/cabot-search huggingface dataset:
Identification and characterization of a new member of the TNF family that induces apoptosis
Authors: Steven R. Wiley, Ken Schooley, Pamela J. Smolak, Wenie S. Din, Chang-Pin Huang, Jillian K. Nicholl, Grant R. Sutherland, Terri Davis Smith, Charles Rauch, Craig A. Smith, Raymond G. Goodwin
Journal: Immunity (1995)
Protective and nonprotective monoclonal antibodies to Cryptococcus neoformans originating from one B cell.
Authors: J Mukherjee, G Nussbaum, M D Scharff, A Casadevall
Journal: The Journal of Experimental Medicine (1995)

Two immunoglobulin M monoclonal antibodies (mAbs) derived from the same B cell recognize different epitopes on the capsular polysaccharide of the pathogenic yeast, Cryptococcus neoformans. Their respective epitopes are located in spatially distinct regions of the capsule. Passive administration of one mAb prolonged survival whereas the other mAb did not. The results indicate that specificity is an important determinant of antibody efficacy against C. neoformans and that somatic mutations occurring during the antibody response can affect the protective efficacy of antibodies to C. neoformans.
Letter: Disco deafness.
Authors: M S Swani
Journal: BMJ (1974)

1/10-1/1,000.Such reactions are abolished if the serum is preheated for 1-hours at 56°C prior to injection.These findings are in contrast to those of Dr. Bryant and his colleagues in that these workers were unable to show attachment of IgE at two and four hours after sensitization.However, they do agree with the findings of other workers who have been able to sensitize chopped human and monkey lung and human skin passively in vitro by ex- posure to IgE antibody for a short time.Our results indicate that human IgE attaches rapidly to macaaue monkey skin and elicits a P.C.A. reaction at two, four, and 24 hours; these reactions being abolished if the serum is heated for 1 hours at 56°C.Most importantly, they emphasize the im- portance of using "clean" experimental monkeys with a known history.-Weare, etc.,
The Sterile Inflammatory Response
Authors: Kenneth L. Rock, Eicke Latz, Fernando Ontiveros, Hajime Kono
Journal: Annual Review of Immunology (2010)

The acute inflammatory response is a double-edged sword. On the one hand, it plays a key role in initial host defense, particularly against many infections. On the other hand, its aim is imprecise, and as a consequence, when it is drawn into battle, it can cause collateral damage in tissues. In situations where the inciting stimulus is sterile, the cost-benefit ratio may be high; because of this, sterile inflammation underlies the pathogenesis of a number of diseases. Although there have been major advances in our understanding of how microbes trigger inflammation, much less has been learned about this process in sterile situations. This review focuses on a subset of the many sterile stimuli that can induce inflammation—specifically dead cells and a variety of irritant particles, including crystals, minerals, and protein aggregates. Although this subset of stimuli is structurally very diverse and might appear to be unrelated, there is accumulating evidence that the innate immune system may recognize them in similar ways and stimulate the sterile inflammatory response via common pathways. Here we review established and emerging data about these responses.
Patterns of disturbed myocardial perfusion in patients with coronary artery disease. Regional myocardial perfusion in angina pectoris.
Authors: A P Selwyn, G Forse, K Fox, A Jonathan, R Steiner
Journal: Circulation (1981)

Fifty patients who presented with angina pectoris were studied to examine the disturbances of regional myocardial perfusion during stress. Each patient underwent 16-point precordial mapping of the ECG during an exercise test, and coronary and left ventricular angiography. Regional myocardial perfusion was assessed using an atrial pacing test and a short-lived radionuclide, krypton-81m. Eleven patients had negative exercise tests and uniform increases in myocardial activity of krypton-81m of 98 +/- 18.0% during pacing. Ten patients performed 30,000-43,000 J in positive exercise tests. These patients showed abnormal coronary anatomy and increases in myocardial activity of krypton-81m to remote and jeopardized myocardium at the onset of pacing. However, further pacing produced a decrease in activity in the affected segment of 68.0 +/- 9.0% accompanied by ST-segment depression and angina. Twelve patients achieved 26,000-32,000 J in positive exercise tests and had significant coronary artery disease. Atrial pacing produced increased activity of krypton-81m to remote myocardium. The jeopardized segment at first showed no change and then a decrease in regional activity of krypton-81m (89.0 +/- 17%) accompanied by ST-segment depression and chest pain. Seventeen patients achieved only 7000-22,000 J in positive exercise tests. These patients showed abnormal coronary anatomy and developed decreases in regional activity of krypton-81m to the affected segment of myocardium starting at the onset of atrial pacing and decreasing by 88 +/- 0 7.0% below control. We conclude that different patterns of disturbed myocardial distribution of krypton-81m are present during stress-induced ischemia in patients with coronary artery disease. There was a close temporal relationship between these disturbances and ST-segment depression.
Y Chromosome Microdeletions and Alterations of Spermatogenesis*
Authors: Carlo Foresta, Enrico Moro, Alberto Ferlin
Journal: Endocrine Reviews (2001)

Three different spermatogenesis loci have been mapped on the Y chromosome and named "azoospermia factors" (AZFa, b, and c). Deletions in these regions remove one or more of the candidate genes (DAZ, RBMY, USP9Y, and DBY) and cause severe testiculopathy leading to male infertility. We have reviewed the literature and the most recent advances in Y chromosome mapping, focusing our attention on the correlation between Y chromosome microdeletions and alterations of spermatogenesis. More than 4,800 infertile patients were screened for Y microdeletions and published. Such deletions determine azoospermia more frequently than severe oligozoospermia and involve especially the AZFc region including the DAZ gene family. Overall, the prevalence of Y chromosome microdeletions is 4% in oligozoospermic patients, 14% in idiopathic severely oligozoospermic men, 11% in azoospermic men, and 18% in idiopathic azoospermic subjects. Patient selection criteria appear to substantially influence the prevalence of microdeletions. No clear correlation exists between the size and localization of the deletions and the testicular phenotype. However, it is clear that larger deletions are associated with the most severe testicular damage. Patients with Y chromosome deletions frequently have sperm either in the ejaculate or within the testis and are therefore suitable candidates for assisted reproduction techniques. This possibility raises a number of medical and ethical concerns, since the use of spermatozoa carrying Y chromosome deletions may produce pregnancies, but in such cases the genetic anomaly will invariably be passed on to male offspring.
Teen Pregnancy Prevention: Do Any Programs Work?
Authors: Josefina J. Card
Journal: Annual Review of Public Health (1999)

▪ Abstract This paper begins with a review of the problem of teen pregnancy in the United States. Domestic trends are compared with those of other developed countries. Antecedents of the problem are discussed. New developments in addressing the problem are then described, including the following: (a) a renewed emphasis on abstinence on the one hand; (b) a move toward a more positive view of teen sexuality on the other; (c) the development of new prevention initiatives such as STD/HIV/AIDS prevention programs, community-wide teen pregnancy prevention collaboratives, broad-based youth development programs, and state and local government initiatives; and (d) the lauching of the National Campaign to Prevent Teen Pregnancy. An analysis of the different ways in which the problem can be framed and the implications for solutions of the problem follow. Examples of promising teen pregnancy and STD/HIV/AIDS prevention programs are provided. The paper ends with a recommendation for an eclectic approach to framing the problem and possible solutions.
Testing Multiregionality of Modern Human Origins
Authors: Naoyuki Takahata, Sang-Hee Lee, Yoko Satta
Journal: Molecular Biology and Evolution (2001)

In order to examine the possibility of multiple founding populations of anatomically modern Homo sapiens, we collected DNA sequence data from 10 X-chromosomal regions, 5 autosomal regions, and 1 Y-chromosomal region, in addition to mitochondrial DNA. Except for five regions which are genealogically uninformative and two other regions for which chimpanzee orthologs are not available, the ancestral sequence and population for each of the remaining regions were successfully inferred. Of these 10 ancestral sequences, 9 occurred in Africa and only 1 occurred in Asia during the Pleistocene. Computer simulation was carried out to quantify the multiregional hypothesis based solely on the premise that there was more than one founding population in the Pleistocene. Allowing the breeding size to vary among the founding populations, the hypothesis may account for the observed African ancestry in 90% of the genomic regions. However, it is required that the founding population in Africa was much larger than that outside Africa. Likelihood estimates of the breeding sizes in the founding populations were more than 9,000 in Africa and less than 1,000 in outside of Africa, although these estimates can be much less biased at the 1% significance level. If the number of African ancestral sequences further increases as more data accumulate in other genomic regions, the conclusion of a single founding population of modern H. sapiens is inevitable.
Autoantibodies in infertility: current opinion
Authors: N Gleicher
Journal: Human Reproduction Update (1998)

The concept of autoimmune-related infertility has remained controversial. Traditionally, abnormal autoimmune function has been implicated as a contributing factor to female as well as male infertility. In the female, abnormal autoimmunity primarily relates to autoantibody activity against ovarian tissue components, whereas in the male, abnormal autoimmunity, believed to be clinically relevant, is mostly directed against the spermatozoon itself. Historically, abnormal autoimmune function has been seen as a rather organ-specific process in both female and male infertility, with either ovarian or testicular antigens as the primary targets. In recent years it has, however, also been recognized that additional, and possibly less organ-specific, processes of autoimmune nature may play a role. For example, female infertility patients have demonstrated a significantly higher incidence of nonorgan-specific autoantibody abnormalities. The incidence of such autoantibody abnormalities appears to be positively correlated to increasing intractability of infertility (Gleicher et al., 1993). On the other hand, there is doubt as to whether such non-organ-specific autoantibodies themselves cause disease or only serve as epiphenomena for a still undefined immunological defect which causes infertility (Gleicher, 1994). Lastly, the newly evolving field of neuroimmunology needs to be considered here. Since reproductive function is under neuroendocrine control, autoimmune processes that affect the hypothalamic–pituitary–gonadal axis at the central nervous system (CNS) level will have considerable impact on infertility. This review will therefore report on autoimmune abnormalities at CNS and gonadal levels and on non-organ-specific abnormalities systemically. It will also separate female from male findings since they are usually distinct, though both can often be found in a single couple presenting with an infertility problem.
Phase I, Dose-Escalation Study of the Targeted Cytotoxic LHRH Analog AEZS-108 in Patients with Castration- and Taxane-Resistant Prostate Cancer
Authors: Stephen V. Liu, Denice D. Tsao-Wei, Shigang Xiong, Susan Groshen, Tanya B. Dorff, David I. Quinn, Yu-Chong Tai, Juergen Engel, Debra Hawes, Andrew V. Schally, Jacek K. Pinski
Journal: Clinical Cancer Research (2014)

AEZS-108, formerly AN-152, is a cytotoxic hybrid molecule consisting of a luteinizing hormone-releasing hormone (LHRH) agonist moiety covalently coupled to doxorubicin, allowing it to deliver doxorubicin selectively to cells expressing LHRH receptors. LHRH receptors are expressed on the cell membrane of many tumors, including prostate cancer. This phase I study determined the maximum tolerated dose (MTD) of AEZS-108 in men with taxane- and castration-resistant prostate cancer (CRPC) while providing additional information on the safety profile and efficacy of this agent.AEZS-108 was administered as an intravenous infusion every 21 days until progression or unacceptable toxicity in cohorts of 3 or 6 patients until the MTD was reached. Blood was collected for capture of circulating tumor cells (CTC) to visualize internalization of AEZS-108, an autofluorescent molecule.The MTD of AEZS-108 in this cohort was 210 mg/m(2), which was lower than that seen in a phase I study conducted in women with endometrial or ovarian cancers. The dose-limiting toxicity was persistent neutropenia. Three patients had a PSA response with an additional 10 patients maintaining PSA stable disease. Of the 10 patients evaluable by RECIST criteria, 9 achieved stable disease. AEZS-108 internalization in CTCs was routinely visualized using its autofluorescence.These findings show that AEZS-108 has an acceptable safety profile and a signal of efficacy, lowering PSA in heavily pretreated patients with prostate cancer, and that internalization of AEZS-108 in prostate cancer CTCs may be a viable pharmacodynamic marker. A phase II study in men with prostate cancer is ongoing.
Cerebral vascular disease and cortical function.
Authors: J V Walther
Journal: BMJ (1977)

grey and breathless in her cot.A tachycardia of 240/min was noted which settled over the following four hours.Examination showed no evidence of cardiac failure.A chest x-ray was normal.An ECG the next morning revealed a sinus tachycardia of 180, min.Her subsequent progress was unevent- ful and she was discharged home on her 65th day weighing 2 42 kg.She failed to keep her follow-up appointmmnt and we later learnt that she had been found dead in her cot unexpectedly at home at the age of 10 weeks.Post-mortem examination revealed no abnormalities.
Coevolution and Life Cycle Specialization of Plant Cell Wall Degrading Enzymes in a Hemibiotrophic Pathogen
Authors: Patrick C. Brunner, Stefano F.F. Torriani, Daniel Croll, Eva H. Stukenbrock, Bruce A. McDonald
Journal: Molecular Biology and Evolution (2013)

Zymoseptoria tritici is an important fungal pathogen on wheat that originated in the Fertile Crescent. Its closely related sister species Z. pseudotritici and Z. ardabiliae infect wild grasses in the same region. This recently emerged host-pathogen system provides a rare opportunity to investigate the evolutionary processes shaping the genome of an emerging pathogen. Here, we investigate genetic signatures in plant cell wall degrading enzymes (PCWDEs) that are likely affected by or driving coevolution in plant-pathogen systems. We hypothesize four main evolutionary scenarios and combine comparative genomics, transcriptomics, and selection analyses to assign the majority of PCWDEs in Z. tritici to one of these scenarios. We found widespread differential transcription among different members of the same gene family, challenging the idea of functional redundancy and suggesting instead that specialized enzymatic activity occurs during different stages of the pathogen life cycle. We also find that natural selection has significantly affected at least 19 of the 48 identified PCWDEs. The majority of genes showed signatures of purifying selection, typical for the scenario of conserved substrate optimization. However, six genes showed diversifying selection that could be attributed to either host adaptation or host evasion. This study provides a powerful framework to better understand the roles played by different members of multigene families and to determine which genes are the most appropriate targets for wet laboratory experimentation, for example, to elucidate enzymatic function during relevant phases of a pathogen's life cycle.
H-2-restricted helper factor secreted by clone hybridoma cells.
Authors: P Lonai, J Puri, S Bitton, Y Ben-Neriah, D Givol, G J Hämmerling
Journal: The Journal of Experimental Medicine (1981)

Biological and serological characteristics of a helper factor secreted by cloned hybridoma cells was described. The factor is carrier specific and contains determinants shared with immunoglobulin VH bu does not react with V kappa- or V lambda-specific antibodies. Presence of four H-2I-controlled antigenic specificities, Ia.ml, Ia.m2, Ia.17, and Ia.m7, was detected. Hence, it is possible that both A beta and E alpha loci may be involved in its control. Helper effect could be obtained only toward B cell sources that shared the H-2K and I-A antigens with the hybridoma cells. Similarly, the factor was absorbed only by spleen cells syngeneic in I-A. Previous studies have demonstrated that this clone binds antigen in an H-2-restricted manner. It follows that H-2-restricted helper cells produce H-2-restricted helper factors. Hence, they support the view that specific T cell factors may represent secreted T cell receptors.
Levamisole and interferon in children with chronic hepatitis B
Authors: Mercedes Ruiz-Moreno, Rosa García, Maria Jose Rua, Beatriz Serrano, Gloria Moraleda, Esperanza Feijoo, Javier Bartolomé, Fernando Ortiz, Inmaculada Castill, Vicente Carreñ
Journal: Hepatology (1993)

To evaluate the possible usefulness of simultaneous administration of levamisole and interferon, we randomly allocated 38 children with chronic hepatitis B to receive either 10 MU/m 2 interferon-α-2a, three times a week for 6 mo (group 1, n = 20) or 90 mg/m 2 of levamisole for 45 days, together with 10 MU/m 2 of interferon-α-2a, three times a week for 6 mo (group 2, n = 18). At the end of the follow-up period (15 mo), no significant differences were observed between the groups with respect to loss of hepatitis B virus DNA and HBeAg from serum and normalization of serum ALT levels. During therapy, a significant increase in the serum levels of ALT and soluble interleukin-2 receptor was observed in both groups but was higher in patients from group 2. The combination of levamisole with interferon was associated with severe side effects. In summary, the combination of levamisole with interferon in children with chronic hepatitis B does not improve the results obtained with interferon alone. (Hepatology 1993;18:264-269).
Role of Monocyte Chemoattractant Protein-1 in Cardiovascular Remodeling Induced by Chronic Blockade of Nitric Oxide Synthesis
Authors: Masamichi Koyanagi, Kensuke Egashira, Shiro Kitamoto, Weihua Ni, Hiroaki Shimokawa, Motohiro Takeya, Teizo Yoshimura, Akira Takeshita
Journal: Circulation (2000)

Background —Chronic inhibition of endothelial nitric oxide (NO) synthesis by the administration of N ω -nitro- l -arginine methyl ester (L-NAME) to rats induces early vascular inflammatory changes (monocyte infiltration into coronary vessels and monocyte chemoattractant protein-1 [MCP-1] expression) as well as subsequent arteriosclerosis (medial thickening and perivascular fibrosis) and cardiac fibrosis. However, the role of MCP-1 in this process is not known. Methods and Results —We investigated the effect of a specific monoclonal anti–MCP-1 neutralizing antibody in rats treated with L-NAME to determine the role of monocytes in the regulation of cardiovascular remodeling. We found increased expression of MCP-1 mRNA in vascular endothelial cells and monocytes in inflammatory lesions. Cotreatment with an anti–MCP-1 antibody, but not with control IgG, prevented the L-NAME–induced early inflammation and reduced late coronary vascular medial thickening. In contrast, the anti–MCP-1 antibody did not decrease the development of perivascular fibrosis, the expression of transforming growth factor (TGF)-β 1 mRNA, or systolic pressure overload induced by L-NAME administration. Conclusions —These results suggest that MCP-1 is necessary for the development of medial thickening as well as monocyte recruitment. In contrast, the pathogenesis of fibrosis may involve other factors, such as TGF-β 1 .
The Effect of Diabetes on B-Type Natriuretic Peptide Concentrations in Patients With Acute Dyspnea
Authors: Alan H.B. Wu, Torbjørn Omland, Philippe Duc, James McCord, Richard M. Nowak, Judd E. Hollander, Howard C. Herrmann, Philippe G. Steg, Cathrine Wold Knudsen, Alan B. Storrow, William T. Abraham, Alberto Perez, Richard Kamin, Paul Clopton, Alan S. Maisel, Peter A. McCullough
Journal: Diabetes Care (2004)

OBJECTIVE—Diabetes has been implicated in reduced myocardial compliance and changes in the intercellular matrix of the myocardium. We determined the effect of diabetes on B-type natriuretic peptide (BNP) concentrations in patients presenting to the emergency department with dyspnea. RESEARCH DESIGN AND METHODS—The Breathing Not Properly Multinational Study was a prospective evaluation of 1,586 patients. A subset of 922 patients was obtained and subdivided into the following groups: group 1 (n = 324), neither diabetes nor heart failure; group 2 (n = 107), diabetes and no heart failure; group 3 (n = 247), no diabetes and heart failure; group 4 (n = 183), both diabetes and heart failure; group 5 (n = 41), heart failure history with no diabetes; and group 6 (n = 20), heart failure history with diabetes. Patients from groups 1, 3, and 5 were matched to groups 2, 4, and 6, respectively, to have the same mean age, sex distribution, BMI, renal function, and New York Heart Association (NYHA) classification (for heart failure). RESULTS—There was no significant difference in median BNP levels between diabetes and no diabetes among no heart failure patients (32.4 vs.32.9 pg/ml), heart failure patients (587 vs. 494 pg/ml), and those with a heart failure history (180 vs. 120 pg/ml). Receiver-operating characteristic curve analysis of the area under the curve for BNP was not different in diabetic versus nondiabetic patients (0.888 vs. 0.878, respectively). However, in a multivariate model, diabetes was an independent predictor of a final diagnosis of heart failure (odds ratio 1.51, 95% CI 1.03–2.02; P &amp;lt; 0.05). CONCLUSIONS—History of diabetes does not impact BNP levels measured in patients with acute dyspnea in the emergency department. Despite the impact of diabetes on the cardiovascular system, diabetes does not appear to confound BNP levels in the emergency department diagnosis of heart failure.