tbuckley/cabot-search huggingface dataset:
HETEROLOGOUS CARRIERS IN THE ANAMNESTIC ANTIHAPTEN RESPONSE
Authors: Marvin B. Rittenberg, Dan H. Campbell
Journal: The Journal of Experimental Medicine (1968)

Anamnestic antihapten responses were obtained to trinitrophenyl (TNP) when rabbits sensitized to trinitrophenyl-hemocyanin (TNP-KLH) were challenged with TNP-heterologous protein conjugates. Hapten-heterologous carrier conjugates elicited antihapten titers similar in magnitude to those elicited by the homologous carrier conjugate. Hapten-heterologous carrier recall of antihapten was successful as early as 37 days and as late as 11 months after sensitization. There was no correlation between anti-TNP-precipitating antibody titer after sensitization and the ability to respond to challenge by hapten-heterologous carrier. The results are discussed in terms of immunogenicity of sensitization, suppressive effects of persisting postsensitization antibody, and submolecular haptenic environment as factors possibly affecting the heterologous recall process.
Systematic genetic risk assessment for breast cancer patients in a community oncology practice
Authors: T. Amatruda, S. Coombes, J. Greenberg, B. Kunz, J. Larsen Haidle, F. Lian, D. Marty, K. Niendorf
Journal: Journal of Clinical Oncology (2008)

22172 Background: In order to increase the identification of patients at risk for hereditary cancers, we developed a systematic genetic risk assessment process for breast cancer patients presenting to oncology services in a multi-center cancer program. Methods: Over a six-month period (September 2006-February 2007), detailed family history forms were provided to both new and returning breast cancer patients at three offices in a community oncology practice. Data from the completed forms were used to generate a four-generation pedigree. The pedigrees were analyzed by a certified genetic counselor and, using published criteria, placed into high, moderate or average risk categories for several hereditary cancer syndromes. Letters summarizing the assessments were sent to the treating oncologists, noting recommendations for referral to genetic services. Oncologist use was then tracked by referral patterns and random chart review for action taken on the information. Satisfaction survey data was obtained through focus groups with participating oncologists and nurses. Results: Of the 548 forms provided, 427 (77.9%) were completed and 117 (27.4%) were assessed at “High Risk” for a hereditary cancer syndrome. Forty-four of the high risk breast cancer syndrome patients (44/98, 45.0%) were referred for genetic counseling services 1 year post provision of genetic assessment. Twenty-five charts were randomly reviewed for oncologist action. Charts from 8/13 (61.5%) of the high or moderate risk patients noted referral for genetic services to date. Significant variation was noted between providers. Satisfaction surveys and focus groups supported continuation of the program, with streamlining and liability as areas of concern. Conclusions: Nearly 1/3 of breast cancer patients in this practice were classified as high risk for an hereditary cancer syndrome. Our intervention was associated with increased referrals for high risk patients as compared to previously published reports. Satisfaction with the process was high among providers and patients alike. Optimal translation of family history information into clinical interventions will require increased efficiency, provider buy-in, development of clinical systems, and quality controls. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Minnesota Affiliate of the Susan G. Komen for the Cure
Treatment of nasopharyngeal carcinoma with Epstein-Barr virus–specific T lymphocytes
Authors: Karin C. M. Straathof, Catherine M. Bollard, Uday Popat, M. Helen Huls, Teresita Lopez, M. Craig Morriss, Mary V. Gresik, Adrian P. Gee, Heidi V. Russell, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop
Journal: Blood (2004)
Regulation of Endothelial Cell Cycle by Laminar Versus Oscillatory Flow
Authors: Deliang Guo, Shu Chien, John Y.-J. Shyy
Journal: Circulation Research (2007)

Steady laminar flow in the straight parts of the arterial tree is atheroprotective, whereas disturbed flow with oscillation in branch points and the aortic root are athero-prone, in part, because of the distinct roles of the flow patterns in regulating the cell cycle of vascular endothelial cells (ECs). To elucidate the molecular basis underlying the endothelial cell cycle regulated by distinct flow patterns, we conducted flow-channel experiments to investigate the effects of laminar versus oscillatory flows on activation of AMP-activated protein kinase (AMPK) and Akt in ECs. Laminar flow caused a transient activation of both AMPK and Akt, but oscillatory flow activated only Akt, with AMPK being maintained at its basal level. Constitutively active and dominant-negative mutants of AMPK and Akt were used to elucidate further the positive effect of Akt and negative role of AMPK in mediating mTOR (mammalian target of rapamycin) and its target p70S6 kinase (S6K) in response to laminar and oscillatory flows. Measurements of phosphorylation of mTOR Ser2448 and S6K Thr389 showed that AMPK, by counteracting Akt under laminar flow, resulted in a transient activation of S6K. Under oscillatory flow, because of the lack of AMPK activation to effect negative regulation, S6K was activated in a sustained manner. As a functional consequence, AMPK activation attenuated cell cycle progression in response to both laminar and oscillatory flows. In contrast, AMPK inhibition promoted EC cycle progression by decreasing the cell population in the G(0)/G(1) phase and increasing it in the S+G(2)/M phase. In vivo, phosphorylation of the promitotic S6K in mouse thoracic aorta was much less than that in mouse aortic root. In contrast, AMPK phosphorylation was higher in the thoracic aorta. These results provide a molecular mechanism by which laminar versus oscillatory flow regulates the endothelial cell cycle.
Lipoproteins as Biomarkers and Therapeutic Targets in the Setting of Acute Coronary Syndrome
Authors: Robert S. Rosenson, H. Bryan Brewer, Daniel J. Rader
Journal: Circulation Research (2014)

The period following an acute coronary syndrome (ACS) represents a critical time frame with a high risk for recurrent events and death. The pathogenesis of this increase in clinical cardiovascular disease events after ACS is complex, with molecular mechanisms including increased thrombosis and inflammation. Dyslipoproteinemia is common in patients with ACS and predictive of recurrent cardiovascular disease events after presentation with an ACS event. Although randomized clinical trials have provided fairly convincing evidence that high-dose statins reduce the risk of recurrent cardiovascular events after ACS, there remain questions about how aggressively to reduce low-density lipoprotein cholesterol levels in ACS. Furthermore, no other lipid-related interventions have yet been proven to be effective in reducing major cardiovascular events after ACS. Here, we review the relationship of lipoproteins as biomarkers to cardiovascular risk after ACS, the evidence for lipid-targeted interventions, and the potential for novel therapeutic approaches in this arena.
The Usefulness of <i>In Vitro</i> Sensitivity Tests in Antibiotic Therapy
Authors: Robert G. Petersdorf, James J. Plorde
Journal: Annual Review of Medicine (1963)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Ankylosing spondylitis in North India: a clinical and immunogenetic study.
Authors: S Prakash, N K Mehra, S Bhargava, M C Vaidya, A N Malaviya
Journal: Annals of the Rheumatic Diseases (1984)

Fifty-one North Indian patients with ankylosing spondylitis (AS) are described with mean age of onset 21.2 years and male to female ratio of 16:1. AS began with peripheral arthritis in 47%, low back pain in 41%, acute anterior uveitis in 10%, and heel pain in 2% of the patients. 76% of 51 patients had one of the extra-axial features of AS: peripheral arthritis (61%), heel pain (24%), anterior uveitis (22%), urethritis (12%), kidney disease (10%), mucosal ulcerations (6%), aortic incompetence (4%), and apical pulmonary fibrosis (4%). A majority (71%) of the patients with peripheral arthritis had mono- or oligoarthritis affecting mainly the lower limb joints. Two patients had coexistent rheumatoid arthritis also. HLA-B27 antigen was detected in 48 (94%) of 51 patients compared with 7 (6%) of 118 controls (relative risk 254; Fisher's exact p = 3.49(-29]. On comparing patients with juvenile onset AS and patients with adult onset disease we found peripheral arthritis to be more frequent at the beginning and during the course of disease in the former.
Pag3/Papα/Kiaa0400, a Gtpase-Activating Protein for Adp-Ribosylation Factor (Arf), Regulates Arf6 in Fcγ Receptor–Mediated Phagocytosis of Macrophages
Authors: Hiroshi Uchida, Akiko Kondo, Yasunori Yoshimura, Yuichi Mazaki, Hisataka Sabe
Journal: The Journal of Experimental Medicine (2001)

The Fcγ receptor (FcγR)-mediated phagocytosis of macrophages is a complex process where remodeling of both the actin-based cytoskeleton and plasma membrane occur coordinately. Several different families of small GTPases are involved. We have isolated a GTPase-activating protein (GAP) for ADP-ribosylation factor (ARF), paxillin-associated protein with ARFGAP activity (PAG)3/Papα/KIAA0400, from mature monocytes and macrophage-like cells. Mammalian ARFs fall into three classes, and the class III isoform (ARF6) has been shown to be involved in FcγR-mediated phagocytosis. Here we report that PAG3 is enriched together with ARF6 and F-actin at phagocytic cups formed beneath immunoglobulin G–opsonized beads in P388D1 macrophages, in which overexpression of ARF6, but not ARF1 (class I) or ARF5 (class II), inhibits the phagocytosis. Overexpression of PAG3, but not its GAP-inactive mutant, attenuated the focal accumulation of F-actin and blocked phagocytosis, although surface levels of the FcγRs were not affected. Other ubiquitously expressed ARFGAPs, G protein–coupled receptor kinase interactors GIT2 and GIT2-short/KIAA0148, which we have shown to exhibit GAP activity for ARF1 in COS-7 cells, did not accumulate at the phagocytic cups or inhibit phagocytosis. Moreover, cooverexpression of ARF6, but not ARF1 or ARF5, restored the phagocytic activity of PAG3-overexpressing cells. We propose that PAG3 acts as a GAP for ARF6 and is hence involved in FcγR-mediated phagocytosis in mouse macrophages.
EFFECT OF RECENT ANTIGEN PRIMING ON ADOPTIVE IMMUNE RESPONSES
Authors: J. Sprent, J. F. A. P. Miller
Journal: The Journal of Experimental Medicine (1974)

When thoracic duct lymphocytes (TDL) or mesenteric lymph node (MLN) cells from mice primed 1 day before with either sheep erythrocytes (SRC) or horse erythrocytes (HRC) were transferred together with both SRC and HRC to irradiated mice, antibody responses measured 7 days later could not be detected to the priming antigen but were high to the other antigen. Furthermore, this unresponsiveness of TDL and MLN to the priming antigen could not be abrogated by delaying antigen challenge of the transferred cells for 1–2 wk. Previous work had shown that short-term priming with antigen also induced specific unresponsiveness in spleen cells on adoptive transfer. Unresponsiveness in these cells, however, was only of temporary duration, full recovery in the reactivity of the cells being observed when challenge with the priming antigen on transfer was delayed for 5 or more days. Since the present work showed that such recovery from initial unresponsiveness on transfer was unique to spleen cells and did not apply to TDL or MLN, it appeared that different mechanisms were responsible for the unresponsiveness in the three populations. It is proposed that the unresponsiveness detected in TDL and MLN cells in the present study resulted from a deficiency of antigen-reactive cells, these cells having been recruited to the spleen, i.e., a region of antigen concentration. This concept of antigen-induced selective recruitment of circulating lymphocytes was supported by evidence that 51Cr-labeled heterologous erythrocytes indeed localized largely in the spleen after intravenous injection but not in MLN.
Renal and systemic oxygen consumption in patients with normal and abnormal renal function.
Authors: B R Kurnik, L S Weisberg, P B Kurnik
Journal: Journal of the American Society of Nephrology (1992)

Systemic and renal oxygen consumption and hemodynamics were studied in patients with normal renal function (NI; serum creatinine concentration (Screat), 1.0 +/- 0.04 mg/dL) and those with moderate chronic renal failure with diabetes mellitus Screat, 2.7 +/- 0.2 mg/dL) or without diabetes mellitus (Screat, 2.4 +/- 0.1 mg/dL). Patients with chronic renal failure were anemic and had normal systemic oxygen consumption (NI, 10,564 +/- 277; chronic renal failure, 9,669 +/- 362 mumol of O2/min) and elevated systemic oxygen extraction (NI, 22.9 +/- 1; chronic renal failure, 30.9 +/- 1.2%) (P less than 0.02). Cardiac output and index and arterial oxygen saturation were equivalent in normal patients and in patients with chronic renal failure. Patients with chronic renal failure had higher renal oxygen extraction (NI, 7.3 +/- 0.8; chronic renal failure, 13.9 +/- 1%), lower RBF (NI, 572 +/- 146; chronic renal failure, 197 +/- 20 mL/min/kidney), and lower renal oxygen consumption per kidney (NI, 391 +/- 101; chronic renal failure, 177 +/- 20 mumol of O2/min/kidney) than did normal patients (P less than 0.02). There was a linear relationship between hemoglobin and RBF (r = 0.47, P less than 0.02). Patients with chronic renal failure and diabetes had lower RBF (diabetes mellitus, 146 +/- 23; without diabetes, 242 +/- 28 mL/min/kidney) and renal oxygen consumption per kidney (diabetes mellitus, 131 +/- 21; without diabetes, 218 +/- 29 mumol of O2/min/kidney (P less than 0.03) but equivalent renal oxygen extraction when compared with patients without diabetes. Patients with chronic renal failure without diabetes mellitus had higher renal oxygen consumption when expressed per 100 mL of creatinine clearance (diabetes mellitus, 1,016 +/- 150; without diabetes mellitus, 1,453 +/- 175 mumol of O2/min/100 mL of creatinine clearance; P less than 0.03). There was a significant linear relationship (P less than 0.005, r = 0.38) between calculated creatinine clearance and renal oxygen consumption with a y intercept representing basal renal oxygen consumption (115 mumol of O2/min/kidney) and a slope of 2.3 mumol of O2/mL. Patients with moderate chronic renal failure have normal systemic oxygen consumption but reduced RBF and renal oxygen consumption. The latter parameters are even lower in patients with chronic renal failure and diabetes. Renal hypermetabolism is more likely to exist in nondiabetic than diabetic renal disease. Basic human renal physiology and pathophysiology are described by the relationships between renal oxygen consumption, blood flow, oxygen extraction, and creatinine clearance in patients with normal and abnormal renal function of varied cause.
Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects
Authors: G S Smith, S L Dewey, J D Brodie, J Logan, S A Vitkun, P Simkowitz, R Schloesser, D A Alexoff, A Hurley, T Cooper, N D Volkow
Journal: American Journal of Psychiatry (1997)

This study was undertaken to measure serotonergic modulation of dopamine in vivo by using positron emission tomography (PET), a radiotracer for the striatal dopamine D2 receptor ([11C]raclopride), and a pharmacologic challenge of the serotonin system (d,l-fenfluramine).Two PET studies using [11C]raclopride were performed in 11 normal male subjects before administration of the serotonin-releasing agent and reuptake inhibitor fenfluramine (60 mg p.o.) and 3 hours afterward. A graphical analysis method was used with the [11C]raclopride data to derive the distribution volume of D2 receptors. Plasma levels of fenfluramine, norfenfluramine, homovanillic acid (HVA), cortisol, and prolactin were determined.Levels of fenfluramine and prolactin were elevated 2 hours after fenfluramine administration and remained significantly elevated during the second scan, while levels of HVA and cortisol were not altered significantly during the time of scanning. A significant decrease in the specific binding (striatum) and the nonspecific binding subtracted from the specific binding (striatum minus cerebellum) of [11C]raclopride was observed. The rate of metabolism of [11C]raclopride and the nonspecific binding (cerebellum) were not significantly altered by the fenfluramine intervention.The observed decrease in [11C]raclopride binding is consistent with an increase in dopamine concentrations and with the ability of serotonin to stimulate dopamine activity. The ability to measure serotonergic modulation of dopamine in vivo may have implications for the study of etiologic and therapeutic mechanisms in schizophrenia, major depressive disorder, obsessive-compulsive disorder, and substance abuse.
Suppression of lymphocyte responses by tuberculous plasma and mycobacterial arabinogalactan. Monocyte dependence and indomethacin reversibility.
Authors: M E Kleinhenz, J J Ellner, P J Spagnuolo, T M Daniel
Journal: Journal of Clinical Investigation (1981)

During tuberculosis, exposure of monocytes to circulating factors may induce the suppressor activity observed in some anergic patients. To explore this possibility, we examined the effects of plasma pooled from 28 untreated tuberculosis (TB) patients and the mycobacterial cell wall polysaccharide D-arabino-D-galactan (AG) on the in vitro function of peripheral blood mononuclear cells (PBMC) from healthy donors. In the [3H] thymidine incorporation assay, stimulated responses of PBMC incubated in culture medium supplemented with TB plasma or co-cultured with 3.0 microgram/ml AG were depressed significantly when compared with control responses. Cytotoxicity and altered kinetics of stimulated DNA synthesis did not contribute to the observed suppression. TB plasma and AG-induced suppression of the PBMC response to purified protein derivative was monocyte dependent and indomethacin reversible. In addition, TB plasma and AG directly inhibited the phytohemagglutinin-stimulated responses of T lymphocytes. In a quantitative assay of monocyte attachment to plastic, both TB plasma and AG significantly increased monocyte adherence from basal levels. These effects on monocyte adherence were reversed with indomethacin or antibody to mycobacterial polysaccharide. In addition, TB plasma passed over an immunoabsorbent column of Sepharose-linked antibody to mycobacterial polysaccharide was depleted of the suppressive and monocyte-adherence augmenting factors. 3.0 microgram/ml AG stimulated a fivefold increase in prostaglandin E2 production by cultured mononuclear cells. Our data suggest that AG circulating alone or bound in immune complexes may account for the observed effects of TB plasma. Similar in vivo exposure may contribute to the cell-mediated suppression of lymphocyte responses in tuberculosis.
Adrenergic influence on concentrating function in the feline gall bladder.
Authors: S Bjorck, R Jansson, J Svanvik
Journal: Gut (1982)

The influence of adrenergic drugs and electrical stimulation of the splanchnic nerves on concentrating function and motility in the feline gall bladder and on heptic bile secretion have been studied in vivo. It was found that electrical stimulation of the splanchnic nerves and adrenergic alpha-receptor stimulation increase the rate of net water absorption from the gall bladder lumen. Adrenergic beta-receptor stimulation relaxed the gall bladder but did not influence the concentrating function. A direct effect on the mucosal cells and/or a ganglionic inhibition of intramural VIP-releasing neurons is suggested as a possible mechanism for the alpha-adrenergic increase of the net water absorption rate. The results are discussed in relation to the adrenergic influence on water absorption in the small intestine. As a functional consequence of an increase in the concentrating activity of the gall bladder in situations of high adrenergic activity a more rapid accumulation of organic contents in its lumen is suggested.
Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia
Authors: Barbara F. Eichhorst, Raymonde Busch, Georg Hopfinger, Rita Pasold, Manfred Hensel, Cordelia Steinbrecher, Siegfried Siehl, Ulrich Jäger, Manuela Bergmann, Stephan Stilgenbauer, Carmen Schweighofer, Clemens M. Wendtner, Hartmut Döhner, Günter Brittinger, Bertold Emmerich, Michael Hallek
Journal: Blood (2005)
Management of the solitary metastasis.
Authors: R McIntosh, N Thatcher
Journal: Thorax (1990)

EditorialsManagement of the solitary metastasis Clinicians are commonly confronted by evidence of initial dissemination of cancer in patients with a known primary tumour.This editorial will discuss the various treatment options for the solitarv metastasis and in particular those factors that predict a favourable our rneafter surgical resection of the metastasis.
Acute Psychological Stress Affects Glucose Concentrations in Patients With Type 1 Diabetes Following Food Intake but not in the Fasting State
Authors: Peter Wiesli, Christoph Schmid, Oranna Kerwer, Christel Nigg-Koch, Richard Klaghofer, Burkhardt Seifert, Giatgen A. Spinas, Kyrill Schwegler
Journal: Diabetes Care (2005)

OBJECTIVE—To compare the effect of acute psychosocial stress on glucose concentrations in the fasting state and following food intake in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—In study 1, 20 patients were exposed to moderate psychosocial stress by means of the Trier Social Stress Test (TSST) in the fasting state. In study 2, the TSST was applied to 20 additional patients 75 min after intake of a standard meal. Glucose concentrations (by continuous glucose monitoring system), blood pressure, and heart rate were monitored on the control day and on the stress testing day. RESULTS—In both studies, blood pressure increased in response to TSST from 122/77 ± 14/9 mmHg at baseline to a maximum of 152/93 ± 21/13 mmHg (P &amp;lt; 0.001), and heart rate increased from 80 ± 11 to 99 ± 19 bpm (P &amp;lt; 0.001). In the fasting state (study 1), glucose concentrations remained unchanged during the control day as well as during the stress testing day. In study 2, glucose concentrations were similar on both days before and up to 75 min after the intake of the standard meal. However, a significant delay (of 45 min) in the decrease of glucose concentrations was induced by psychological stress. A two-factor repeated-measures ANOVA revealed a significant difference of glucose concentrations over time (F = 646.65/P &amp;lt; 0.001). CONCLUSIONS—In the postprandial period, acute psychological stress induced a significantly delayed decrease of glucose concentrations, whereas in the fasting state, no effect on poststress glucose concentrations was observed.