tbuckley/cabot-search huggingface dataset:
Nitric Oxide Promotes Proliferation and Plasminogen Activator Production by Coronary Venular Endothelium Through Endogenous bFGF
Authors: Marina Ziche, Astrid Parenti, Fabrizio Ledda, Patrizia Dell’Era, Harris J. Granger, Carlo A. Maggi, Marco Presta
Journal: Circulation Research (1997)

We reported previously that NO is responsible for the angiogenesis produced by endothelium-dependent vasodilating peptides. To investigate the mechanisms by which NO controls angiogenesis, NO was assessed for the ability to affect cell proliferation and upregulation of urokinase-type plasminogen activator (uPA) induced by basic fibroblast growth factor (bFGF) when added exogenously to or when produced endogenously by coronary venular endothelial cells (CVECs). The treatment of the cells with the NO donor sodium nitroprusside (NaNp) induced uPA upregulation and cell proliferation, which were prevented by anti-bFGF antibodies. Similarly, the NO-dependent mitogenic activity of the vasodilating peptide substance P (SP) was blocked by anti-bFGF antibodies, thus implicating endogenous bFGF in the NO-induced response. NaNp and SP induced bFGF expression as measured by Western blot analysis of CVEC extracts and by differential reverse transcriptase-polymerase chain reaction of bFGF mRNA. SP-induced upregulation of bFGF was prevented by the NO synthase inhibitor N omega-monomethyl-L-arginine. We conclude that NO promotes cell proliferation and uPA upregulation in CVECs by inducing endogenous bFGF and that this pathway mediates the angiogenetic response to the vasoactive neuropeptide SP. This signaling paradigm may provide an important link between shear rate, NO, bFGF, and coronary angiogenesis.
Detergent Properties of Bile Salts: Correlation with Physiological Function
Authors: A F Hofmann, D M Small
Journal: Annual Review of Medicine (1967)

The aphorism, To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all (210), applies aptly to bile salts:6 for to consider the function of bile salts in ignorance of their physical properties is to be deprived of many helpful concepts; conversely, studies of the physical properties of bile salts which have been carried out in ignorance of their physiological functions have overlooked many of their distinctive properties. l �.This review summarizes the authors' views of information presently available o n the physical properties of bile salts in solution and at interfaces, both of which are relevant to their physiological function. The detergent
A subset of memory CD4+ helper T lymphocytes identified by expression of Pgp-1.
Authors: K Butterfield, C G Fathman, R C Budd
Journal: The Journal of Experimental Medicine (1989)

The Pgp-1 glycoprotein (Ly-24 antigen) is acquired by mature murine T lymphocytes at the time of primary antigen stimulation Pgp-1 was previously shown to be a useful cell surface marker for distinguishing antigen-specific memory CD8+ T lymphocytes after immunization. Here we demonstrate that this observation extends to CD4+ T lymphocytes. Antigen-specific CD4+ T cells in mice immunized with sperm whale myoglobin or keyhole limpet hemocyanin were contained nearly exclusively in the minor Pgp-1+ subset.
Immune response towards the amino-terminus of desmoglein 1 prevails across different activity stages in nonendemic pemphigus foliaceus
Authors: P.T. Chan, B. Ohyama, K. Nishifuji, K. Yoshida, K. Ishii, T. Hashimoto, M. Amagai
Journal: British Journal of Dermatology (2010)

Background Pemphigus foliaceus (PF) is a blistering skin disease mediated by antibodies to desmoglein (Dsg) 1. The two major subtypes are nonendemic and endemic PF. A previous study in endemic PF demonstrated that changes in antibody epitope could modulate disease relapse and remission. Objectives To characterize the frequency of immunoreactivity to various Dsg1 extracellular (EC) domains in nonendemic PF and to study if there is any change in epitope profile across various activity stages. Methods Sera from 34 patients with nonendemic PF were selected. To map the conformational epitopes by immunoprecipitation-immunoblotting, we constructed five Dsg1/Dsg2 domain-swapped molecules, with each molecule representing one EC domain of Dsg1 on a backbone of Dsg2. Results Dsg1 EC1, EC2, EC3, EC4 and EC5 domains were recognized by 88%, 50%, 13%, 22% and 0% of active PF sera, respectively. Immunoreactivity to EC3 or EC4 often cosegregated with that to either EC1 or EC2. Longitudinal follow-up of 21 patients with PF for a median of 16 months revealed that, in most cases, immunoreactivity to the amino-terminus of Dsg1 persisted across various activity stages; only two patients lost their EC1 reactivity upon remission and changed their major epitope(s) to EC2 ± EC3. Conclusions Most of the anti-Dsg1 antibodies in nonendemic PF bind to the amino-terminus of Dsg1, a region critical for intercellular adhesion of cadherins, and this skewed amino-terminal immunoreactivity prevails across various activity stages in most patients, even upon remission. These findings are valuable for understanding the biology of Dsg-mediated cellular adhesion as well as for the development of epitope-based monitoring and therapeutic strategies.
Membrane-Bound Interleukin (IL)-15 on Renal Tumor Cells Rescues Natural Killer Cells from IL-2 Starvation-Induced Apoptosis
Authors: Sebastian Wittnebel, Sylvie Da Rocha, Julien Giron-Michel, Abdelali Jalil, Paule Opolon, Bernard Escudier, Pierre Validire, Krystel Khawam, Salem Chouaib, Bruno Azzarone, Anne Caignard
Journal: Cancer Research (2007)

Abstract Renal cell carcinoma primary tumors and lung metastases are infiltrated by activated natural killer (NK) cells. Interleukin (IL)-15, a major cytokine involved in cross-talk between accessory cells (dendritic cells and macrophages) and NK cells, is produced by epithelial renal cells. We show that renal cell carcinoma cells and normal renal cells express IL-15 mRNA and membrane-bound IL-15 (MbIL-15). These cells also express IL-15 receptor α (IL-15Rα). Silencing of IL-15Rα by specific small interfering RNA in renal cell carcinoma had no effect on MbIL-15 production, indicating that the cytokine is not cross-presented by IL-15Rα in renal cell carcinoma cells but anchored to the membrane. Furthermore, we show that MbIL-15 from renal cell carcinoma cells is functional and involved in rapid nuclear translocation of phosphorylated signal transducers and activators of transcription 3 in IL-2–starved NK cells. MbIL-15 on the target did not interfere with resting NK cell activation and target cell cytolysis but rescued NK cells from IL-2 starvation-induced apoptosis through contact-dependent interaction. Masking of MbIL-15 with soluble IL-15Rα molecules restored NK cell apoptosis. These findings suggest that IL-15 produced by renal tumor cells is involved in the maintenance of active NK cells at the tumor site. [Cancer Res 2007;67(12):5594–9]
Comment on Grunberger “Insulin Analogs—Are They Worth It? Yes!” Diabetes Care 2014;37:1767–1770 and Davidson “Insulin Analogs—Is There a Compelling Case to Use Them? No!” Diabetes Care 2014;37:1771–1774
Authors: Dario Giugliano, Michela Petrizzo, Maria Ida Maiorino, Giuseppe Bellastella, Katherine Esposito
Journal: Diabetes Care (2014)

We applaud the initiative of Diabetes Care to provide an in-depth discussion on the role of insulin analogs as compared with regular insulins in the treatment of diabetes. Both Grunberger (1) and Davidson (2) present valuable arguments to defend their positions; however, our feeling is that the arguments provided cannot influence, to a large extent, clinicians’ decision about their use as in many parts of the world clinicians have no role in the battle between local regulatory agencies and big pharma. So, if a clinician is convinced about the superiority of any insulin analog over the human insulin counterpart, his or her scientific conviction will remain …
Extreme risk taker who wants to continue taking part in high risk sports after serious injury
Authors: M Pain, J H Kerr
Journal: British Journal of Sports Medicine (2004)

The case is reported of a 40 year old male high risk sport athlete who had seriously injured himself several times and as a result was partially physically disabled and had trouble with mental tasks requiring concentration such as spelling, reading numbers, and writing. The athlete was referred to a sports psychologist. In consultations, it became clear that he was having difficulty reconciling the difference between his life as it used to be and as it would be in the future. Part of his difficulty was dealing with the frustration and anger "outbursts" which resulted from not being able to perform straightforward everyday motor skills. In spite of his injuries and disability, the patient badly wanted to continue participating in extreme sports. Reversal theory is used in the discussion to provide theoretical explanations of the motivation for his extreme risk taking behaviour.
Hydrogen Peroxide-Induced Gene Expression across Kingdoms: A Comparative Analysis
Authors: K. Vandenbroucke, S. Robbens, K. Vandepoele, D. Inze, Y. Van de Peer, F. Van Breusegem
Journal: Molecular Biology and Evolution (2008)

Cells react to oxidative stress conditions by launching a defense response through the induction of nuclear gene expression. The advent of microarray technologies allowed monitoring of oxidative stress–dependent changes of transcript levels at a comprehensive and genome-wide scale, resulting in a series of inventories of differentially expressed genes in different organisms. We performed a meta-analysis on hydrogen peroxide (H2O2)–induced gene expression in the cyanobacterium Synechocystis PCC 6803, the yeast Saccharomyces cerevisiae and Schizosaccharomyces pombe, the land plant Arabidopsis thaliana, and the human HeLa cell line. The H2O2-induced gene expression in both yeast species was highly conserved and more similar to the A. thaliana response than that of the human cell line. Based on the expression characteristics of genuine antioxidant genes, we show that the antioxidant capacity of microorganisms and higher eukaryotes is differentially regulated. Four families of evolutionarily conserved eukaryotic proteins could be identified that were H2O2 responsive across kingdoms: DNAJ domain–containing heat shock proteins, small guanine triphosphate-binding proteins, Ca2+-dependent protein kinases, and ubiquitin-conjugating enzymes.
THE PROBLEM OF BRAIN TUMOR IN PSYCHIATRIC DIAGNOSIS
Authors: HOWARD D. MCINTYRE, AURELIA P. MCINTYRE
Journal: American Journal of Psychiatry (1942)

Brain tumor is found at necropsy in from 3.5 per cent, 6.7 per cent to 13.5 per cent in state hospital material. Brain tumor may occur in a patient with a major psychosis in which instance it is not necessarily the cause of psychotic symptoms but will undoubtedly aggravate them. Here the problem of the psychiatrist is to recognize the symptoms of a progressive neurologic disorder running concomitant with the symptoms of the major psychosis. An illustrative case is presented. Far more important are those cases of brain tumor in which the tumor is the cause of the presenting mental symptoms. Meningiomas arising from the olfactory groove are the most important from a psychiatric standpoint because they are benign and operable. If Foster Kennedy's syndrome is well understood and evaluated these tumors can be recognized much earlier and more frequently than they now are. The brain tumor problem in psychiatry is almost as important as is the problem of syphilis, and it furnishes one of several good reasons for not making too great a separation between neurology and psychiatry. Such diagnoses as Alzheimer's disease, Pick's disease, arteriosclerotic dementia, encephalitis, and Parkinson's disease should be regarded with a high degree of suspicion until tumor has been ruled out. The burden of proof certainly rests on the psychiatric diagnostician. We as psychiatrists should become more "brain tumor conscious" and air injection should be employed more frequently than it is employed in psychiatric clinics. When it is remembered that the meningioma, a benign operable tumor is the most common tumor producing mental symptoms there is all the more reason for improving our diagnostic skill in recognizing tumor as a cause of mental symptoms. Illustrative cases are presented together with necropsy, operative and encephalographic studies in patients in whom one or more examiners failed to recognize tumor as the cause of the psychotic symptoms.
Prevalence Rates of Male and Female Sexual Violence Perpetrators in a National Sample of Adolescents
Authors: Michele L. Ybarra, Kimberly J. Mitchell
Journal: JAMA Pediatrics (2013)

IMPORTANCE Sexual violence can emerge in adolescence, yet little is known about youth perpetrators-especially those not involved with the criminal justice system. OBJECTIVE To report national estimates of adolescent sexual violence perpetration and details of the perpetrator experience. DESIGN, SETTING, AND PARTICIPANTS Data were collected online in 2010 (wave 4) and 2011 (wave 5) in the national Growing Up With Media study. Participants included 1058 youths aged 14 to 21 years who at baseline read English, lived in the household at least 50% of the time, and had used the Internet in the last 6 months. Recruitment was balanced on youths' biological sex and age. MAIN OUTCOMES AND MEASURES Forced sexual contact, coercive sex, attempted rape, and completed rape. RESULTS Nearly 1 in 10 youths (9%) reported some type of sexual violence perpetration in their lifetime; 4% (10 females and 39 males) reported attempted or completed rape. Sixteen years old was the mode age of first sexual perpetration (n = 18 [40%]). Perpetrators reported greater exposure to violent X-rated content. Almost all perpetrators (98%) who reported age at first perpetration to be 15 years or younger were male, with similar but attenuated results among those who began at ages 16 or 17 years (90%). It is not until ages 18 or 19 years that males (52%) and females (48%) are relatively equally represented as perpetrators. Perhaps related to age at first perpetration, females were more likely to perpetrate against older victims, and males were more likely to perpetrate against younger victims. Youths who started perpetrating earlier were more likely than older youths to get in trouble with caregivers; youths starting older were more likely to indicate that no one found out about the perpetration. CONCLUSIONS AND RELEVANCE Sexual violence perpetration appears to emerge earlier for males than females, perhaps suggesting different developmental trajectories. Links between perpetration and violent sexual media are apparent, suggesting a need to monitor adolescents' consumption of this material. Victim blaming appears to be common, whereas experiencing consequences does not. There is therefore urgent need for school programs that encourage bystander intervention as well as implementation of policies that could enhance the likelihood that perpetrators are identified.
Concentrations of some antibiotics in synovial fluid after oral administration, with special reference to antistaphylococcal activity.
Authors: M A Sattar, S P Barrett, M I Cawley
Journal: Annals of the Rheumatic Diseases (1983)

One of 4 antibiotics with antistaphylococcal activity was given in a conventional oral dose for one day to each of 20 hospitalised patients with synovial effusion of a knee joint requiring aspiration. Serial synchronous samples of serum and synovial fluid (SF) were taken over 36 hours through indwelling cannulae. No morbidity was experienced either during or after this procedure. Satisfactory antistaphylococcal concentrations in SF were achieved with sodium fusidate (500 mg 8 hourly) and amoxycillin (250 mg 8 hourly). Cephradine (500 mg 6 hourly) frequently failed to reach the minimum inhibitory concentration for Staphylococcus aureus in the SF, and flucloxacillin (250 mg 6 hourly) was unpredictable in its penetration of the synovial space. Wide interpatient variation of both serum and SF concentrations was found. Our results indicate that sodium fusidate is an appropriate early treatment for a nonresistant staphylococcal joint infection. Amoxycillin is a suitable alternative or second antistaphylococcal drug and would also be appropriate initial therapy when the infecting organism is unknown. We strongly recommend that SF antibiotic concentrations be measured, to ensure adequate penetration of the synovial cavity, in the treatment of septic arthritis.
In Vivo Molecular Chemotherapy and Noninvasive Imaging With an Infectivity-Enhanced Adenovirus
Authors: A. Hemminki
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Adenovirus-based gene therapy is a promising approach to treat advanced cancers that are resistant to other treatments. However, many primary cells lack the requisite coxsackie-adenovirus receptor (CAR), limiting the in vivo efficacy of gene therapy. Recently, a modified adenovirus that is not dependent on CAR expression for infectivity was developed. We used noninvasive imaging to investigate the in vivo antitumor efficacy of gene therapy using this adenovirus in an animal model of ovarian cancer. Methods: The adenoviral vectors RGDTKSSTR (CAR-independent) and AdTKSSTR (CAR-dependent) express herpes simplex virus thymidine kinase (TK) for molecular chemotherapy and the human somatostatin receptor subtype 2 (SSTR) for noninvasive nuclear imaging. Subcutaneous or peritoneal human xenograft ovarian cancers were established from highly aggressive SKOV3.ip1 cells in immune-deficient mice. Adenoviral constructs were infected intratumorally or intraperitoneally once a day for 3 days. Control mice received three injections, one per day, of Ad5Luc1, a CAR-dependent adenoviral vector that includes a luciferase marker gene. The somatostatin analogue 99mTc-P2045 was used for noninvasive in vivo imaging of RGDTKSSTR that was injected into subcutaneous tumors. For mice with peritoneal tumors, survival was compared among the different treatment groups using Kaplan–Meier analysis with the log-rank statistic. All statistical tests were two-sided. Results: Tumor-associated RGDTKSSTR could be detected 15 days after introduction of the vector. In the subcutaneous model, tumors injected with RGDTKSSTR were statistically significantly smaller than those injected with AdTKSSTR (P<.001). In the intraperitoneal model, mice treated with RGDTKSSTR lived longer (survival at day 45 = 63.6%; 95% confidence interval [CI] = 35.2% to 92.0%) than those treated with AdTKSSTR (survival at day 45 = 0%) or Ad5Luc1 (survival at day 45 = 18.1%; 95% CI = 0.0% to 41.0%). Discussion: RGDTKSSTR shows antitumor efficacy against ovarian cancer in vivo in animal models. The virus can be imaged noninvasively and may have the potential to be a useful agent for treating ovarian cancer.
Identification of a transiently exposed VE-cadherin epitope that allows for specific targeting of an antibody to the tumor neovasculature
Authors: Chad May, Jacqueline F. Doody, Rashed Abdullah, Paul Balderes, Xiaohong Xu, Chien Peter Chen, Zhenping Zhu, Lawrence Shapiro, Paul Kussie, Daniel J. Hicklin, Fang Liao, Peter Bohlen
Journal: Blood (2005)
Allelic Exclusion in pTα-deficient Mice: No Evidence for Cell Surface Expression of Two T Cell Receptor (TCR)-β Chains, but Less Efficient Inhibition of Endogeneous Vβ→ (D)Jβ Rearrangements in the Presence of a Functional TCR-β Transgene
Authors: Anna Krotkova, Harald von Boehmer, Hans Jörg Fehling
Journal: The Journal of Experimental Medicine (1997)

Although individual T lymphocytes have the potential to generate two distinct T cell receptor (TCR)-β chains, they usually express only one allele, a phenomenon termed allelic exclusion. Expression of a functional TCR-β chain during early T cell development leads to the formation of a pre-T cell receptor (pre-TCR) complex and, at the same developmental stage, arrest of further TCR-β rearrangements, suggesting a role of the pre-TCR in mediating allelic exclusion. To investigate the potential link between pre-TCR formation and inhibition of further TCR-β rearrangements, we have studied the efficiency of allelic exclusion in mice lacking the pre-TCR-α (pTα) chain, a core component of the pre-TCR. Staining of CD3+ thymocytes and lymph node cells with antibodies specific for Vβ6 or Vβ8 and a pool of antibodies specific for most other Vβ elements, did not reveal any violation of allelic exclusion at the level of cell surface expression. This was also true for pTα-deficient mice expressing a functionally rearranged TCR-β transgene. Interestingly, although the transgenic TCR-β chain significantly influenced thymocyte development even in the absence of pTα, it was not able to inhibit fully endogeneous TCR-β rearrangements either in total thymocytes or in sorted CD25+ pre-T cells of pTα−/− mice, clearly indicating an involvement of the pre-TCR in allelic exclusion.
Complete nucleotide sequences of bovine alpha S2- and beta-casein cDNAs: comparisons with related sequences in other species.
Authors: A F Stewart, J Bonsing, C W Beattie, F Shah, I M Willis, A G Mackinlay
Journal: Molecular Biology and Evolution (1987)

The nucleotide sequences corresponding to bovine alpha S2- and beta-casein mRNAs have been determined by cDNA analysis. Both sequences appear to be complete at their 5' ends. The nucleotide sequence of alpha S2-casein, when compared with the corresponding cavine A sequence, helps to define the boundaries of a large amino acid repeat (approximately 80 residues) whereas comparisons with the nucleotide sequences of rat gamma- and mouse epsilon-casein mRNAs also reveal extensive sequence similarities. An alignment of these four sequences shows that the divergence of their translated regions has been characterized by the duplication and deletion of discrete segments of sequence that probably correspond to exons. A high degree of nucleotide substitution is also found when the four sequences are compared, except for well-conserved leader-peptide and phosphorylation-site sequences and, to a lesser extent, the 5'-untranslated regions. Similar comparison of the bovine and rat beta-caseins shows that their divergence has involved a high rate of nucleotide substitution but that no major insertions or deletions of sequence have occurred. The several splice sites that have veen defined in the rat beta-casein gene are likely to have been conserved in the bovine. The contrasting evolutionary histories of the alpha- and beta-casein coding sequences correlate with the distinctive functions of these proteins in the casein micelle system in milk.
Menopause and Postmenopausal Hormone Use and Risk of Incident Kidney Stones
Authors: Holly J. Mattix Kramer, Francine Grodstein, Meir J. Stampfer, Gary C. Curhan
Journal: Journal of the American Society of Nephrology (2003)

Menopause is associated with increased urinary calcium excretion, which could increase the risk for the development of calcium-containing kidney stones. However, it is unknown whether menopause and postmenopausal hormone (PMH) use are independent risk factors for incident kidney stone disease in women. Data from 91,731 female Nurses' Health Study participants who provided information on diet, menopause status, and kidney stone disease were used to examine the independent association between menopause and PMH use and risk of incident kidney stones. No association was found between menopause and incident kidney stones in age-adjusted (relative risk [RR], 1.07; 95% CI, 0.85 to 1.34) or multivariate models (RR, 1.12; 95% CI, 0.89 to 1.41). However, when the association between the type of menopause and risk of incident kidney stones was examined, surgical menopause was associated with an increased risk in both the age-adjusted (RR, 1.37; 95% CI, 1.05 to 1.77) and multivariate models (RR, 1.39; 95% CI, 1.07 to 1.81), whereas natural menopause was not. Compared with never-use, past or current PMH use (including duration of PMH use) was not associated with incident kidney stones among postmenopausal women. In conclusion, no association was found between menopause and PMH use and incident kidney stones. Surgical menopause, however, may be associated with an increased risk.