tbuckley/cabot-search huggingface dataset:
The timing of TCRα expression critically influences T cell development and selection
Authors: Troy A. Baldwin, Michelle M. Sandau, Stephen C. Jameson, Kristin A. Hogquist
Journal: The Journal of Experimental Medicine (2005)

Sequential rearrangement of the T cell receptor for antigen (TCR) β and α chains is a hallmark of thymocyte development. This temporal control is lost in TCR transgenics because the α chain is expressed prematurely at the CD4−CD8− double negative (DN) stage. To test the importance of this, we expressed the HYα chain at the physiological CD4+CD8+ double positive (DP) stage. The reduced DP and increased DN cellularity typically seen in TCR transgenics was not observed when the α chain was expressed at the appropriate stage. Surprisingly, antigen-driven selection events were also altered. In male mice, thymocyte deletion now occurred at the single positive or medullary stage. In addition, no expansion of CD8αα intestinal intraepithelial lymphocytes (IELs) was observed, despite the fact that HY transgenics have been used to model IEL development. Collectively, these data establish the importance of proper timing of TCR expression in thymic development and selection and emphasize the need to use models that most accurately reflect the physiologic process.
The natriuretic and hypotensive effects of potassium.
Authors: D B Young, R E McCaa, Y J Pan, A C Guyton
Journal: Circulation Research (1976)

The chronic effects of potassium loading on sodium balance and related variables were studied in two groups of dogs. The first group was intact except for the presence of indwelling arterial and venous cannulas. On the 1st day, increasing daily potassium intake from a normal level (30 mEq/day) to 200 mEq/day produced a 0.47-mEq increase in plasma potassium with a 56% increase (P greater than 0.01) in sodium excretion in spite of a 58% increase in plasma aldosterone concentration. After 6 days of potassium loading the cumulative negative sodium balance averaged 44 mEq while 22Na space decreased 6.7% (P less than 0.025). In this group arterial pressure did not change measurably. The same experimental protocol was repeated in a second group of dogs that were chronically adrenalectomized and maintained on fixed levels of aldosterone (50 mug/day) and hydrocortisone (1 mg/day). With aldosterone levels held constant the same increase in potassium intake produced a 1st day increase in potassium concentration of 1.20 mEq/liter and 217% (P less than 0.001) increase in sodium excretion. After 5 days of high potassium intake, the cumulative negative sodium balance totaled 84 mEq. Sodium space decreased 7.5% (P less than .005) during the course of the 5-day high potassium intake period. Potassium loading caused a fall in mean arterial pressure in this group; pressure fell from the control level of 110 +/- mm Hg to 87 +/- 4 mm Hg (P less than .001) after 3 days of high intake. By the 5th day of the experiment, pressure stabilized at 96 +/- 3 mm Hg, 13% less than (P less than 0.01) the control level. The results suggest that changes in plasma potassium concentration within physiological limits may have long term effects on sodium balance.
Specificity of fc receptors for IgG2a, IgG1/IgG2b, and IgE on rat macrophages.
Authors: G Boltz-Nitulescu, H Bazin, H L Spiegelberg
Journal: The Journal of Experimental Medicine (1981)

To characterize the Fc receptors on rat alveolar and peritoneal macrophages (M phi), we analyzed their ability to form rosettes with fixed ox erythrocytes (Eo') coated with myeloma proteins of all rat Ig classes and with fresh erythrocytes (Eo) sensitized with rat IgG1 and IgG2, rabbit IgG and IgM, and mouse IgA antibodies. The M phi formed rosettes with Eo' coated with rat myeloma proteins of classes IgG1, IgG2a, IgG2b, and IgE but not IgG2c, IgA, IgM, and IgD. Rat M phi also formed rosettes with Eo' coated with human IgG1, IgG3, IgG4, mouse IgG1, IgG2a, IgG2b, and rabbit IgG. Furthermore, rat M phi formed rosettes with Eo sensitized with rat IgG1, IgG2, or rabbit IgG antibodies but not with Eo sensitized with rabbit IgM or mouse IgA antibodies. Trypsin treatment of rat M phi abolished IgG1/IgG2b and IgE but not IgG2a rosettes. The IgG2a and IgE rosettes were Ig class specific because they were inhibited only by rat IgG2a and rat IgE, respectively. In contrast, IgG1 and IgG2b rosettes were inhibited equally by IgG1 and IgG2b. Heterologous IgG inhibited IgG1/IgG2b but not IgG2a rosettes. Rat IgE inhibited rat IgG1, IgG2b, and heterologous IgG rosette formation on rat M phi. Although Eo' coated with rat IgE formed rosettes with mouse P388D1 macrophagelike cells, rat IgE did not inhibit IgG rosettes on these cells. Similarly, Eo' coated with human IgE formed rosettes with human U937 macrophage-like cells, but human IgE did not inhibit IgG rosettes on these cells. The results indicate that rat M phi have at least three distinct Fc receptors: one is specific for rat IgG2a and is trypsin resistant; a second is specific for rat IgE and is trypsin sensitive; and a third reacts with rat IgG1 rat IgG2b, and heterologous IgG and is trypsin sensitive. Rat IgE inhibited IgG1/IgG2b rosettes undirectionally and uniquely on rat M phi.
Aspiration of oocytes for in-vitro fertilization
Authors: R Horne
Journal: Human Reproduction Update (1996)

An aspiration system, incorporating a regulated vacuum pump, was used to examine, in vitro, some factors that may affect oocyte collection. In an open aspiration system, as the length of the needle was increased, or the internal diameter decreased, the velocity (and flow rate) of aspirated fluid decreased. There was a difference, however, between experimental flows and those predicted by Hagen-Poiseuille's Law. Upon application of vacuum to a closed aspiration system, employing isolated bovine ovaries, there was an initial rapid increase in the collection tube vacuum to 85% of the selected pump vacuum followed by a more gradual rise to 100%. The vacuum within the needle similarly rose rapidly to approximately half the selected vacuum, while the vacuum at the needle tip was ~5% of selected vacuum. The vacuums throughout the system briefly equilibrated as maximum flow/velocity was reached. Flow/velocity slowed dramatically as the follicle collapsed, and stopped as the needle tip was blocked. If vacuum was maintained during the withdrawal of the needle from the follicle, there was a dramatic forward flow of fluid toward the collection tube. The morphological appearance of bovine cumulus after in-vitro aspiration was generally unaltered by vacuums commonly utilized in oocyte collection, providing the cumulus was regular, compact and refractile. The cumulus was less resistant to aspiration if it was damaged or had degenerated. These results suggest that an intact cumulus may offer protection during ooocyte collection.
Macrophage Inflammatory Protein-3α Is a Novel Serum Marker for Nasopharyngeal Carcinoma Detection and Prediction of Treatment Outcomes
Authors: Kai-Ping Chang, Sheng-Po Hao, Jui-Hung Chang, Chih-Ching Wu, Ngan-Ming Tsang, Yun-Shien Lee, Chen-Lung Hsu, Shir-Hwa Ueng, Shiau-Chin Liu, Yu-Lun Liu, Pei-Cih Wei, Yin Liang, Yu-Sun Chang, Jau-Song Yu
Journal: Clinical Cancer Research (2008)

Abstract Purpose: We herein examine whether macrophage inflammatory protein-3α (MIP-3α) is a biomarker for nasopharyngeal carcinoma (NPC) and whether it is involved in modulating NPC cell functions. Experimental Design: The study population comprises 275 NPC patients and 250 controls. MIP-3α levels in tissues and sera were examined by immunohistochemistry and ELISA, respectively. EBV DNA load and EBV viral capsid antigen IgA were measured by quantitative real-time PCR and immunofluorescence assay, respectively. Effects of MIP-3α on NPC cell motility were investigated by Transwell migration/invasion assays and RNA interference. Results: MIP-3α was overexpressed in NPC tumor cells. Serum MIP-3α levels were significantly higher in untreated patients, recurrent patients and patients with distant metastases versus non-NPC controls, patients with complete remission, and long-term disease-free patients. In the prospective cohort, serum MIP-3α levels were significantly higher in untreated NPC patients with advanced tumor-node-metastasis stage versus early stage and also correlated with EBV DNA load. Measurement of MIP-3α, EBV DNA, and viral capsid antigen IgA levels in serial serum/plasma samples from treated patients at 6-month intervals revealed a high association between MIP-3α level, EBV DNA load, and disease status. Among 155 consecutive NPC patients, subjects with pretreated MIP-3α serum levels over 65 pg/mL had worse prognoses for overall survival and distant metastasis-free survival in univariate and multivariate analysis. Additionally, cell functional assays showed that MIP-3α contributed to migration and invasion of NPC cells, which could be effectively inhibited by MIP-3α knockdown. Conclusions: MIP-3α may be a novel biomarker and prognosticator for NPC and is involved in migration and invasion of NPC cells.
Climate variation and incidence of Ross river virus in Cairns, Australia: a time-series analysis.
Authors: S Tong, W Hu
Journal: Environmental Health Perspectives (2001)

In this study we assessed the impact of climate variability on the Ross River virus (RRv) transmission and validated an epidemic-forecasting model in Cairns, Australia. Data on the RRv cases recorded between 1985 and 1996 were obtained from the Queensland Department of Health. Climate and population data were supplied by the Australian Bureau of Meteorology and the Australian Bureau of Statistics, respectively. The cross-correlation function (CCF) showed that maximum temperature in the current month and rainfall and relative humidity at a lag of 2 months were positively and significantly associated with the monthly incidence of RRv, whereas relative humidity at a lag of 5 months was inversely associated with the RRv transmission. We developed autoregressive integrated moving average (ARIMA) models on the data collected between 1985 to 1994, and then validated the models using the data collected between 1995 and 1996. The results show that the relative humidity at a lag of 5 months (p &lt; 0.001) and the rainfall at a lag of 2 months (p &lt; 0.05) appeared to play significant roles in the transmission of RRv disease in Cairns. Furthermore, the regressive forecast curves were consistent with the pattern of actual values.
NCCN Biosimilars White Paper: Regulatory, Scientific, and Patient Safety Perspectives
Authors: Andrew D. Zelenetz, Islah Ahmed, Edward Louis Braud, James D. Cross, Nancy Davenport-Ennis, Barry D. Dickinson, Steven E. Goldberg, Scott Gottlieb, Philip E. Johnson, Gary H. Lyman, Richard Markus, Ursula A. Matulonis, Denise Reinke, Edward C. Li, Jessica DeMartino, Jonathan K. Larsen, James M. Hoffman
Journal: Journal of the National Comprehensive Cancer Network (2011)

Biologics are essential to oncology care. As patents for older biologics begin to expire, the United States is developing an abbreviated regulatory process for the approval of similar biologics (biosimilars), which raises important considerations for the safe and appropriate incorporation of biosimilars into clinical practice for patients with cancer. The potential for biosimilars to reduce the cost of biologics, which are often high-cost components of oncology care, was the impetus behind the Biologics Price Competition and Innovation Act of 2009, a part of the 2010 Affordable Care Act. In March 2011, NCCN assembled a work group consisting of thought leaders from NCCN Member Institutions and other organizations, to provide guidance regarding the challenges health care providers and other key stakeholders face in incorporating biosimilars in health care practice. The work group identified challenges surrounding biosimilars, including health care provider knowledge, substitution practices, pharmacovigilance, naming and product tracking, coverage and reimbursement, use in off-label settings, and data requirements for approval.
Prostate-Specific Antigen (PSA) and PSA Density: Racial Differences in Men Without Prostate Cancer
Authors: R. J. Henderson, J. A. Eastham, C. Daniel J., T. Whatley, J. Mata, D. Venable, M. W. Kattan, O. Sartor
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Many physicians now use serum prostatespecific antigen (PSA) to screen for prostate cancer in asymptomatic men. Whether or not a prostate biopsy should also be performed depends on an accurate definition of what constitutes a normal PSA value. Until recently, studies conducted to establish normal serum PSA values have involved study populations that have included few African-American men. Purpose: We sought to compare serum PSA levels and PSA density (i.e., serum PSA level/prostate volume ratio) in African-American and white men without histologic evidence of prostate cancer. Methods: We reviewed the medical records of 826 consecutive men who underwent one or more prostate biopsies at the Veterans Affairs Medical Center in Shreveport, LA, from January 1993 through December 1995. In this retrospective review, we recorded patient's age, race, serum PSA level, digital rectal examination result, ultrasound- determined prostate volume, indications for biopsy, and biopsy results. Data from a total of 752 consecutive men who were either white or African-American and whose indication for biopsy included a serum PSA of greater than 4.0 ng/mL and/or an abnormal digital rectal examination were analyzed. To examine possible differences in serum PSA level, PSA density, prostate volume, and patient age, the two-sided Student's t test was employed. Multivariate linear regression analysis was used to determine if serum PSA levels were associated with the patient's age, race, or prostate volume in men without prostate cancer. Results: Of the 752 men included in this analysis, 254 had histologic evidence of prostate cancer and 498 did not. Of the 498 men without prostate cancer, 367 (74%) men were white and 131 (26%) were black. There were no racial differences in age or calculated prostate volume. Serum PSA levels and calculated PSA density, however, were significantly (both P <.0001) higher in African-American men than in white men. A multivariate linear regression analysis indicated that race and prostate volume were independent variables associated with serum PSA level. For African-American and white men, serum PSA values of greater than 4 ng/mL were associated with prostate cancer with sensitivities of 89.5% and 81.9%, respectively, and specificities of 38.2% and 52.3%, respectively. Conclusion: Among biopsied men without histologic evidence of prostate cancer, African-Americans have a significantly higher PSA level and PSA density than similarly aged white men. Implications: Published criteria for normal PSA level and density have been derived primarily from white men and may not be directly applicable to other populations. Race-specific data are needed to fully optimize PSA as a tumor marker in racial populations that are at high risk for prostate cancer death
Serum glycoproteins in coronary artery disease.
Authors: S Snyder, E L Coodley, B C Durham, R S Pennock
Journal: Circulation (1977)

Serum glycoprotein levels were compared in two groups of age- and sex-matched patients, 15 with coronary artery disease and 14 normal controls. While total glycoprotein levels were increased in the coronary group, significantly higher levels were found in only five of 16 glycoproteins--C3c haptoglobin, GC-globulin, alpha1-acid glycoprotein, and C3 activator--with no change in 10 other glycoproteins and significant decrease in transferrin. This study demonstrates what appears to be a glycoprotein profile in coronary artery disease and reviews possible interactions of glycoproteins with known risk factors in atherogenesis.
Interpretation of increases in the transfer coefficient for carbon monoxide (TLCO/VA or KCO).
Authors: D J Lipscomb, K Patel, J M Hughes
Journal: Thorax (1978)

During a 15-month period, 27 patients were seen in a routine clinical pulmonary function laboratory in whom the transfer coefficient (TLCO/VA or KCO), measured by the single breath technique, was increased. Pulmonary haemorrhage accounted for two-thirds of the cases; in them sequential measurements of KCO were able to monitor the onset and cessation of bleeding. In the remaining cases the cause of the increase in KCO remains uncertain. All patients had a reduction in vital capacity. Experiments in six normal subjects showed that KCO rose as the breath-holding lung volume was reduced, but that this was insufficient to account for the raised KCO in patients with reduced volumes. Partitioning of the two components of TLCO at different lung volumes in three normal subjects showed that an increase in pulmonary capillary blood volume per unit alveolar volume was chiefly responsible for the increase of KCO in normal subjects at lower lung volumes. The membrane diffusing capacity changed less than predicted per unit volume, suggesting that the thickness of the air-blood barrier remains fairly constant as the lung expands or contracts.
A CASE OF ACUTE LYMPHAEMIA
Authors: E. J. McWeeney
Journal: BMJ (1905)

ACUTE LYMIHAEMIA.[M"n 401 divided nuclei were always quite distinguishable by the characters given above from the ordinary polynuclear leuco- cyte; a coarse finger-like or amoeboid-looking lobulation was the commonest condition.Many of these large cells seemed very labile, and had been traumatized in the act of making the film.This was evidenced by the loss of the protoplasm of some, and by the spreading out of others into a delicate reticulated or vacuolated layer of basophilic matter very irregular in shape.A considerable number of these possessed protoplasm with a greater amount of basophilia than the nucleus, which was then disernible with difficulty as a clear, almost hyaline, mass embedded in or seemingly apposed to the darkly-stained protoplasm.No evidence of mitotic activity was observed in any of the leucocytes in this blood.3. The second variety of mononuclear cell comprising 32 per cent.was smaller, and its nucleus took the basic stain much more deeply.It was sometimes round, sometimes reniform.In triacid preparations the so-called " perinuclear granules of Neisser," now regarded as artefacts, showed a peculiar predilection for these lymphocytic nuclei.The pro- toplasm was usually quite scanty, occasionally moreabundant, and decidedly basophilic, so that when the bulk of the cell was larger than normal, and its nucleus a little less basophilic, a difficulty arose in the distinction of this from the larger variety of mononuclear cell.4. Most cells were not specially stained for, and no undoubted specimen was seen in the Jenner preparation.5. Glycogen in finely granular form was readily detected in many of the leucocytes.This case agrees with the clinical pictures of acute leukaemia in its sudden onset, rapid course, moderate enlargement of lymph glands, enlargement of spleen, haemorrhages in skin and mucous membranes, and oral fetor.It agrees with the haemocytic picture of -acute leukaemia in the following points: (i) Enormous preponderance of hyaline mononuclear cells, the larger variety preponderating as it is said by Ewing2 and others 'to do in acute cases' and in children;(2) rarity of polynuclear neutrophiles, and, indeed, of all forms of granule cells; (3) presence of myelocytes in very small numbers; (4) rarity of both varieties of nucleated red cor- puscles, as was first pointed out by A. Fraenkel.3We have no hesitation in diagnosing the case as acute leukaemia.A dis- cussion of the significance of the blood changes in this interesting case, and of their relation to changes in the bloodforming organs, would, we consider, be lacking in objectivity unless accompanied by the results of autopsy, which we unfortunately have not at our disposal.We therefore abstain from entering on so difficult a task, merely referring to the recent papers of Glinski, ' Lustgarten,5 Januschkiewicz, and Parkes Weber,7 as well as to Pappenheim's complete survey8 of the current theories as to the origin of the blood corpuscles.
The Oregon Health Plan — Lessons for the Nation
Authors: Thomas Bodenheimer
Journal: New England Journal of Medicine (1997)

In 1989, the state of Oregon embarked on a controversial experiment in the financing of health care. The state planned to add many uninsured people to the Medicaid program and to pay for this expansion by reducing the Medicaid benefit package — more people would be covered, but for fewer services. The Oregon plan provides important lessons to a nation striving to expand health care coverage in an era of shrinking budgets.At first, the Oregon plan made repeated headlines and provoked strong criticism. “The Oregon plan will target a new group for discrimination — the seriously ill,” wrote an . . .
S100A8 and S100A9 are novel nuclear factor kappa B target genes during malignant progression of murine and human liver carcinogenesis
Authors: Julia Németh, Ilan Stein, Daniel Haag, Astrid Riehl, Thomas Longerich, Elad Horwitz, Kai Breuhahn, Christoffer Gebhardt, Peter Schirmacher, Meinhard Hahn, Yinon Ben-Neriah, Eli Pikarsky, Peter Angel, Jochen Hess
Journal: Hepatology (2009)

The nuclear factor-kappaB (NF-kappaB) signaling pathway has been recently shown to participate in inflammation-induced cancer progression. Here, we describe a detailed analysis of the NF-kappaB-dependent gene regulatory network in the well-established Mdr2 knockout mouse model of inflammation-associated liver carcinogenesis. Expression profiling of NF-kappaB-deficient and NF-kappaB-proficient hepatocellular carcinoma (HCC) revealed a comprehensive list of known and novel putative NF-kappaB target genes, including S100a8 and S100a9. We detected increased co-expression of S100A8 and S100A9 proteins in mouse HCC cells, in human HCC tissue, and in the HCC cell line Hep3B on ectopic RelA expression. Finally, we found a synergistic function for S100A8 and S100A9 in Hep3B cells resulting in a significant induction of reactive oxygen species (ROS), accompanied by enhanced cell survival.We identified S100A8 and S100A9 as novel NF-kappaB target genes in HCC cells during inflammation-associated liver carcinogenesis and provide experimental evidence that increased co-expression of both proteins supports malignant progression by activation of ROS-dependent signaling pathways and protection from cell death.
Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase
Authors: Alfredo Ramirez, André Heimbach, Jan Gründemann, Barbara Stiller, Dan Hampshire, L Pablo Cid, Ingrid Goebel, Ammar F Mubaidin, Abdul-Latif Wriekat, Jochen Roeper, Amir Al-Din, Axel M Hillmer, Meliha Karsak, Birgit Liss, C Geoffrey Woods, Maria I Behrens, Christian Kubisch
Journal: Nature Genetics (2006)
SCHIZOPHRENIA IN TRIPLETS: A FAMILY STUDY
Authors: DONALD G. LANGSLEY, THOMAS P. BURTON, MIRA GRISWOLD, HANK WALZER, RONALD B. SPINKA
Journal: American Journal of Psychiatry (1963)

We report a case of schizophrenia in triplets in which 2 monozygotic sisters are affected and a fraternal brother is not. Prolonged clinical investigation of the family has revealed major differences in the form, symptomatology, and depth or regression exhibited by the 2 sisters. A genetic hypothesis by itself is felt not to account for the differences in the manifestations of the illness. Various psychogenetic hypotheses including such areas as confusion of identity, disturbances in primary object relations, social isolation, pathological communications and psychopathology of role models for identification all derive some support from the family study. The identification of one girl (Janet) with mother and the other (Jeanine) with father is felt to account for behavior differences before and during the psychosis.