tbuckley/cabot-search huggingface dataset:
Activation-induced apoptosis in human macrophages: developmental regulation of a novel cell death pathway by macrophage colony-stimulating factor and interferon gamma.
Authors: D H Munn, A C Beall, D Song, R W Wrenn, D C Throckmorton
Journal: The Journal of Experimental Medicine (1995)

Activated macrophages (M phi s) are important participants in host defense, but their uncontrolled activation leads rapidly to septic shock and death. One mechanism for regulating other dangerous cells in the immune system is programmed cell death, or apoptosis. Monocytes are known to undergo spontaneous apoptosis upon leaving the circulation unless provided with specific survival signals, but mature tissue M phi s are more robust cells, and it was not clear that they could be similarly regulated by apoptosis. We now show that during differentiation monocytes rapidly lose their sensitivity to apoptosis triggered by passive cytokine withdrawal, but they may retain a novel pathway which initiates apoptosis after activation with specific stimuli (zymosan and phorbol esters). Sensitivity to activation-induced apoptosis was developmentally determined, being downregulated by the maturation-promoting cytokine macrophage colony-stimulating factor but stably upregulated by even transient exposure to the proinflammatory cytokine interferon gamma (IFN-gamma). Apoptosis began within 2-4 h of activation, occurred in &amp;gt; 95% of susceptible cells, and in mixed cocultures selectively affected only those M phi s with a history of IFN-gamma priming. Consistent with a possible role for protein kinase C in the signaling pathway leading to cell death, the kinase inhibitor staurosporine was protective against both phorbol ester- and zymosan-induced apoptosis. Our studies describe a novel form of activation-induced M phi apoptosis which is developmentally regulated by two physiologically relevant cytokines. We speculate that apoptosis may serve to restrict the destructive potential of inflammatory M phi s.
Androgen Receptor– and E2F-1–Targeted Thymoquinone Therapy for Hormone-Refractory Prostate Cancer
Authors: Ahmed O. Kaseb, Kannagi Chinnakannu, Di Chen, Arun Sivanandam, Sheela Tejwani, Mani Menon, Q. Ping Dou, G. Prem-Veer Reddy
Journal: Cancer Research (2007)

Relapse of prostate cancer after androgen ablation therapy is hormone-refractory, with continued tumor growth being dependent on the androgen receptor (AR). E2F-1, a regulator of cell proliferation and viability, reportedly plays a role in the development of hormone-refractory prostate cancer. Thymoquinone is a component of Nigella sativa, an herb used for thousands of years for culinary and medicinal purposes in Asian and Middle Eastern countries and has been reported to have an antineoplastic effect both in vitro and in vivo. We observed that thymoquinone inhibited DNA synthesis, proliferation, and viability of cancerous (LNCaP, C4-B, DU145, and PC-3) but not noncancerous (BPH-1) prostate epithelial cells by down-regulating AR and E2F-1. In LNCaP cells, this was associated with a dramatic increase in p21(Cip1), p27(Kip1), and Bax. Thymoquinone blunted progression of synchronized LNCaP cells from G1 to S phase, with a concomitant decrease in AR and E2F-1 as well as the E2F-1-regulated proteins necessary for cell cycle progression. In a xenograft prostate tumor model, thymoquinone inhibited growth of C4-2B-derived tumors in nude mice. This in vivo suppression of tumor growth, as with C4-2B cell growth in culture, was associated with a dramatic decrease in AR, E2F-1, and cyclin A as determined by Western blot of tissue extracts. Tissue immunohistochemical staining confirmed a marked reduction in E2F-1 and showed induction of apoptosis on terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling assay. These findings show that thymoquinone suppresses the expression of AR and E2F-1 necessary for proliferation and viability of androgen-sensitive as well as androgen-independent prostate cancer cells both in vitro and in vivo and, moreover, produced no noticeable side effects in mice. We conclude that thymoquinone, a naturally occurring herbal product, may prove to be effective in treating hormone-sensitive as well as hormone-refractory prostate cancer. Furthermore, because of its selective effect on cancer cells, we believe that thymoquinone can also be used safely to help prevent the development of prostate cancer.
Role of the collecting duct in the regulation of sodium balance.
Authors: J H Stein, M A Kirschenbaum, W H Bay, R W Osgood, T F Ferris
Journal: Circulation Research (1975)

A large body of evidence has accumulated which demonstrates that sodium transport in some distal nephron segment is altered in response to changes in extracellular fluid volume. Sodium reabsorption in the loop of Henle and distal tubule is directly related to delivery rate and is not inhibited by volume expansion. In contrast, recent studies have shown that Ringer loading causes a greater natriuretic response than hyperoncotic albumin because of diminished collecting duct sodium transport in the former model. Additional studies in animals with different basal extracellular fluid volumes and in DOCA-escape rats indicate further that the collecting duct is an important regulator of sodium balance. Although the factors that modulate sodium transport in the collecting duct are not clear, it is postulated that the local release of prostaglandins may be of major importance.
Local understandings of vulnerability and protection during the neonatal period in Sylhet district, Bangladesh: a qualitative study
Authors: Peter J Winch, M Ashraful Alam, Afsana Akther, Dilara Afroz, Nabeel Ashraf Ali, Amy A Ellis, Abdullah H Baqui, Gary L Darmstadt, Shams El Arifeen, M Habibur Rahman Seraji
Journal: The Lancet (2005)
Prophylaxis for venous thromboembolism during treatment for cancer: questionnaire survey
Authors: C C Kirwan
Journal: BMJ (2003)

Venous thromboembolism is common in patients with cancer and is often the cause of death.1 Patients receiving treatment for cancer are at even greater risk of thromboembolism. Thromboembolism occurs in 5% of patients receiving chemotherapy for early breast carcinoma,2 and up to 17.6% of patients receiving chemotherapy for metastatic breast disease are affected.3 Patients with node-negative breast cancer taking tamoxifen were six times more likely to develop venous thromboembolism.4

Adjuvant use of tamoxifen carries a relative risk of 1.22 compared with no treatment. Combining methods of treatment further increases the risk of thromboembolism. Chemotherapy with tamoxifen increases risk by 3.5 times compared with chemotherapy alone,5 and preoperative radiotherapy for rectal carcinoma doubles the postoperative risk of venous thrombosis.5 Low doses (1 mg) of warfarin …
Natural Killer T Cell Activation Protects Mice Against Experimental Autoimmune Encephalomyelitis
Authors: Avneesh K. Singh, Michael T. Wilson, Seokmann Hong, Danyvid Olivares-Villagómez, Caigan Du, Aleksandar K. Stanic, Sebastian Joyce, Subramaniam Sriram, Yasuhiko Koezuka, Luc Van Kaer
Journal: The Journal of Experimental Medicine (2001)

Experimental autoimmune encephalomyelitis (EAE) serves as a prototypic model for T cell–mediated autoimmunity. Vα14 natural killer T (NKT) cells are a subset of T lymphocytes that recognize glycolipid antigens presented by the nonpolymorphic major histocompatibility complex (MHC) class I–like protein CD1d. Here, we show that activation of Vα14 NKT cells by the glycosphingolipid α-galactosylceramide (α-GalCer) protects susceptible mice against EAE. β-GalCer, which binds CD1d but is not recognized by NKT cells, failed to protect mice against EAE. Furthermore, α-GalCer was unable to protect CD1d knockout (KO) mice against EAE, indicating the requirement for an intact CD1d antigen presentation pathway. Protection of disease conferred by α-GalCer correlated with its ability to suppress myelin antigen-specific Th1 responses and/or to promote myelin antigen-specific Th2 cell responses. α-GalCer was unable to protect IL-4 KO and IL-10 KO mice against EAE, indicating a critical role for both of these cytokines. Because recognition of α-GalCer by NKT cells is phylogenetically conserved, our findings have identified NKT cells as novel target cells for treatment of inflammatory diseases of the central nervous system.
Petit Mal Epilepsy
Authors: Samuel Livingston
Journal: JAMA (1965)

Since the advent of electroencephalography, it has been clearly demonstrated that all epileptic seizures of brief duration are not petit mal. It is important that the physician who cares for epileptic patients be cognizant of this fact, since the treatment and prognosis of petit mal epilepsy differ in most respects from that of other types of epilepsy. Petit mal epilepsy is primarily a disorder of childhood and seldom continues into adulthood. It is a comparatively rare type of epileptic spell: of 15,102 epileptic patients, only 364 (2.3%) had "true" petit mal epilepsy. It is a relatively benign disturbance and rarely causes demonstrable evidence of pathological cerebral changes, except in those patients who have frequent attacks of petit mal status. Since patients with petit mal epilepsy are prone to develop major seizures, concurrent administration of petit mal and major motor anticonvulsants (combined therapy) is recommended.
Mutational Analysis of the Active Site and Antibody Epitopes of the Complement-inhibitory Glycoprotein, CD59
Authors: Dale L. Bodian, Simon J. Davis, B. Paul Morgan, Neil K. Rushmere
Journal: The Journal of Experimental Medicine (1997)

The Ly-6 superfamily of cell surface molecules includes CD59, a potent regulator of the complement system that protects host cells from the cytolytic action of the membrane attack complex (MAC). Although its mechanism of action is not well understood, CD59 is thought to prevent assembly of the MAC by binding to the C8 and/or C9 proteins of the nascent complex. Here a systematic, structure-based mutational approach has been used to determine the region(s) of CD59 required for its protective activity. Analysis of 16 CD59 mutants with single, highly nonconservative substitutions suggests that CD59 has a single active site that includes Trp-40, Arg-53, and Glu-56 of the glycosylated, membrane-distal face of the disk-like extracellular domain and, possibly, Asp-24 positioned at the edge of the domain. The putative active site includes residues conserved across species, consistent with the lack of strict homologous restriction previously observed in studies of CD59 function. Competition and mutational analyses of the epitopes of eight CD59-blocking and non-blocking monoclonal antibodies confirmed the location of the active site. Additional experiments showed that the expression and function of CD59 are both glycosylation independent.
Association of Estrogen Levels With Neuropsychological Performance in Women With Schizophrenia
Authors: Anne L. Hoff, William S. Kremen, Mary H. Wieneke, John Lauriello, Howard M. Blankfeld, William O. Faustman, John G. Csernansky, Thomas E. Nordahl
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: This study sought to determine the relationship of estrogen levels with psychiatric symptoms and neuropsychological function in female patients with schizophrenia. METHOD: Psychiatric symptoms were assessed and average estrogen and progesterone levels from four consecutive weekly blood samples were measured in 22 female inpatients with schizophrenia who were also administered a neuropsychological battery. RESULTS: There were strong positive correlations between average estrogen level and cognitive function, especially measures of global cognitive function, verbal and spatial declarative memory, and perceptual-motor speed. Correlations of hormone levels with psychiatric symptoms were nonsignificant. CONCLUSIONS: Higher estrogen levels in female patients with schizophrenia are associated with better cognitive ability. These results may have implications for potential treatment of cognitive dysfunction with adjunctive estrogen in female patients with schizophrenia.
Topical tretinoin (retinoic acid) improves melasma. A vehicle-controlled, clinical trial
Authors: C. E. M. GRIFFITHS, L. J. FINKEL, C. M. DITRE, T. A. HAMILTON, C. N. ELLIS, J.J. VOORHEES
Journal: British Journal of Dermatology (1993)

Journal Article Topical tretinoin (retinoic acid) improves melasma. A vehicle‐controlled, clinical trial Get access C. E. M. GRIFFITHS, C. E. M. GRIFFITHS Dermatopharmacology Unit, Department of Dermatology, University of Michigan Medical Center, Ann Arbo, Michigan, U.S.A. Dr C.E.M. Griffiths, Department of Dermatology, University of Michigan Medical Center, 1910 Taubman Health Care Center, 1500 East Medical Center Drive. Ann Arbor, Michigan 48109–0314. U.S.A. Search for other works by this author on: Oxford Academic Google Scholar L. J. FINKEL, L. J. FINKEL Dermatopharmacology Unit, Department of Dermatology, University of Michigan Medical Center, Ann Arbo, Michigan, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar C. M. DITRE, C. M. DITRE Dermatopharmacology Unit, Department of Dermatology, University of Michigan Medical Center, Ann Arbo, Michigan, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar T. A. HAMILTON, T. A. HAMILTON Dermatopharmacology Unit, Department of Dermatology, University of Michigan Medical Center, Ann Arbo, Michigan, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar C. N. ELLIS, C. N. ELLIS Dermatopharmacology Unit, Department of Dermatology, University of Michigan Medical Center, Ann Arbo, Michigan, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar J.J. VOORHEES J.J. VOORHEES Dermatopharmacology Unit, Department of Dermatology, University of Michigan Medical Center, Ann Arbo, Michigan, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 4, 1 October 1993, Pages 415–421, https://doi.org/10.1111/j.1365-2133.1993.tb03169.x Published: 01 October 1993 Article history Accepted: 23 April 1993 Published: 01 October 1993
LESSONS FROM 12 YEARS OF COMPARATIVE RISK PROJECTS
Authors: Ken Jones, Heidi Klein
Journal: Annual Review of Public Health (1999)

▪ Abstract Can an analytical tool for comparing environmental risks and policy activities be used to evaluate their relative efficacy in ultimately changing the allocation of public funds? Some insight is possible through a review of comparative risk projects that have been carried out at the city, state, and national levels, as well as among Indian tribes, over the past 12 years. The lessons from this review should apply to the field of public health. For every comparison of environmental issues, such as clean-air standards with fish consumption advisories, there is a parallel discussion of public health priorities and strategies, such as antismoking and pregnancy prevention programs, immunization programs and disease surveillance efforts, or well-baby clinics and food safety programs. Lessons from comparative risk projects and processes may offer the public health community new ways of thinking about using stakeholder assessment processes in developing public health policy.
Studies on the intestinal flora : Part II Bacterial flora of the small intestine in patients with gastrointestinal disorders
Authors: B. S. Drasar, M. Shiner
Journal: Gut (1969)

The type and distribution of bacteria in the jejunal juice of patients with a variety of gastrointestinal conditions that might affect the small intestinal flora were examined. Bacterial colonization of the jejunum defined, in this context, as the occurrence of a bile salttolerant flora consisting of both aerobic and anaerobic bacteria qualitatively resembling that of faeces, was observed only in patients with some form of blind loop. Prominent among the bacteria isolated from these colonized juices were non-sporing anaerobic bacteria, most usually Bacteroides, able to hydrolyse bile salts. No simple correlation between the patient's fat excretion and bacterial colonization of the jejunum could be demonstrated.
In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia
Authors: Jesús Agulla, David Brea, Francisco Campos, Tomás Sobrino, Bárbara Argibay, Wajih Al-Soufi, Miguel Blanco, José Castillo, Pedro Ramos-Cabrer
Journal: Theranostics (2014)

The use of theranostics in neurosciences has been rare to date because of the limitations imposed on the free delivery of substances to the brain by the blood-brain barrier.Here we report the development of a theranostic system for the treatment of stroke, a leading cause of death and disability in developed countries.We first performed a series of proteomic, immunoblotting and immunohistological studies to characterize the expression of molecular biomarkers for the so-called peri-infarct tissue, a key region of the brain for stroke treatment.We confirmed that the HSP72 protein is a suitable biomarker for the peri-infarct region, as it is selectively expressed by at-risk tissue for up to 7 days following cerebral ischemia.We also describe the development of anti-HSP72 vectorized stealth immunoliposomes containing imaging probes to make them traceable by conventional imaging techniques (fluorescence and MRI) that were used to encapsulate a therapeutic agent (citicoline) for the treatment of cerebral ischemia.We tested the molecular recognition capabilities of these nano-platforms in vitro together with their diagnostic and therapeutic properties in vivo, in an animal model of cerebral ischemia.Using MRI, we found that 80% of vectorized liposomes were located on the periphery of the ischemic lesion, and animals treated with citicoline encapsulated on these liposomes presented lesion volumes up to 30% smaller than animals treated with free (non-encapsulated) drugs.Our results show the potential of nanotechnology for the development of effective tools for the treatment of neurological diseases.
An even more universal model of reading: Various effects of orthography on dyslexias
Authors: Naama Friedmann, Aviah Gvion
Journal: Behavioral and Brain Sciences (2012)

Abstract The properties of a specific orthography dictate the way people read it. We bring considerations from dyslexia to suggest that the claim can be extended further. First, the effect of orthographic neighborhood density can be extended beyond letter-position encoding and beyond the orthographic lexicon. Second, Hebrew and Arabic differ with respect to letter forms, and hence, in letter-position encoding.
Role of calmodulin in platelet aggregation. Structure-activity relationship of calmodulin antagonists.
Authors: M Nishikawa, H Hidaka
Journal: Journal of Clinical Investigation (1982)

Two series of derivatives of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), including a dechlorinated analog of W-7 (W-5) and various aminoalkyl chain analogs of W-7 (A-3, A-4, A-5, I-240, A-6) were synthesized and their structure-activity relationships with calmodulin antagonistic actions and their potencies in inhibiting human platelet aggregation in vitro were investigated. Their binding affinities to calmodulin in the presence of 100 microM Ca2+ were dependent both on the chlorination of the naphthalene ring and on the length of aminoalkyl chain. The ability of these derivatives to inhibit Ca2+-dependent phosphorylation of 20,000-dalton myosin light chain from platelets correlated well with the magnitude of their binding affinity to calmodulin. W-7(10-100 microM) inhibited in a dose-dependent manner platelet aggregation induced by collagen (2 micrograms/ml), ADP (5 microM), epinephrine (1 microgram/ml), sodium arachidonate (0.83 mM), thrombin (0.125 U/ml), and A-23187 (10 microM). The IC50 value (concentration producing 50% inhibition of aggregation) of W-7 was lower in arachidonate- and collagen-induced aggregation than in ADP- or epinephrine-induced aggregation. A good correlation between the potency in inhibition of collagen-induced aggregation by W-7 and its derivatives and their affinities to calmodulin was obtained (r = 0.94). Thus, the inhibitory mechanism of these compounds may be due to their effect on Ca2+-calmodulin-dependent processes, such as 20,000-dalton myosin light chain phosphorylation. These data also support the hypothesis that the calmodulin-mediated system has an important role in platelet function.
Driving Pressure and Survival in the Acute Respiratory Distress Syndrome
Authors: Marcelo B.P. Amato, Maureen O. Meade, Arthur S. Slutsky, Laurent Brochard, Eduardo L.V. Costa, David A. Schoenfeld, Thomas E. Stewart, Matthias Briel, Daniel Talmor, Alain Mercat, Jean-Christophe M. Richard, Carlos R.R. Carvalho, Roy G. Brower
Journal: New England Journal of Medicine (2015)

Mechanical-ventilation strategies that use lower end-inspiratory (plateau) airway pressures, lower tidal volumes (VT), and higher positive end-expiratory pressures (PEEPs) can improve survival in patients with the acute respiratory distress syndrome (ARDS), but the relative importance of each of these components is uncertain. Because respiratory-system compliance (CRS) is strongly related to the volume of aerated remaining functional lung during disease (termed functional lung size), we hypothesized that driving pressure (ΔP=VT/CRS), in which VT is intrinsically normalized to functional lung size (instead of predicted lung size in healthy persons), would be an index more strongly associated with survival than VT or PEEP in patients who are not actively breathing.
NITROGEN CYCLING IN THE GUT
Authors: Malcolm F. Fuller, Peter J. Reeds
Journal: Annual Review of Nutrition (1998)

▪ Abstract This review examines the involvement of the gastrointestinal tract in the utilization of nitrogen, the identities of the nitrogenous substances entering and leaving the gut, and the significance of this recycling in the overall nitrogen economy of the body. It is concerned with nonruminant mammals, including man.
Humoral response to wheat protein in patients with coeliac disease and enteropathy associated T cell lymphoma.
Authors: C O'Farrelly, C Feighery, D S O'Briain, F Stevens, C E Connolly, C McCarthy, D G Weir
Journal: BMJ (1986)

Features that might distinguish uncomplicated coeliac disease from enteropathy associated T cell lymphoma were investigated. Of 76 patients with coeliac disease, 71 (93%) had raised levels of alpha gliadin antibody and all responded clinically and histologically to treatment with a gluten free diet. In contrast, none of 16 patients with enteropathy associated T cell lymphoma had raised levels of alpha gliadin antibody, and treatment with a gluten free diet resulted in histological improvement in one and transient clinical improvement in six patients. The ratio of women to men was 2.2:1 in the group with coeliac disease and 1:1.6 in the patients with enteropathy associated T cell lymphoma. Thus patients with enteropathy associated T cell lymphoma do not display a humoral immune response to wheat protein (alpha gliadin), rarely respond to a gluten free diet, and are often men. Patients with uncomplicated coeliac disease usually have raised levels of alpha gliadin antibody, always respond to a gluten free diet, and are frequently women. These findings suggest the presence of two separate forms of enteropathy: one is benign and sensitive to wheat protein whereas the other runs a malignant course.