tbuckley/cabot-search huggingface dataset:
Target tissue sensitivity, testosterone– social environment interactions, and lattice hierarchies
Authors: Kathleen C. Chambers
Journal: Behavioral and Brain Sciences (1998)

The following three points are made. One must consider not only the levels of circulating hormone but the target tissue upon which the hormone acts. Increased testosterone levels alone do not account for differences in displayed intermale aggression, because testosterone and social environment interact in complex ways to influence behavior. A given behavior can be triggered by multiple motivational systems.
Deficiency of the NR4A Neuron-Derived Orphan Receptor-1 Attenuates Neointima Formation After Vascular Injury
Authors: Takashi Nomiyama, Yue Zhao, Florence Gizard, Hannes M. Findeisen, Elizabeth B. Heywood, Karrie L. Jones, Orla M. Conneely, Dennis Bruemmer
Journal: Circulation (2009)

The neuron-derived orphan receptor-1 (NOR1) belongs to the evolutionary highly conserved and most ancient NR4A subfamily of the nuclear hormone receptor superfamily. Members of this subfamily function as early-response genes regulating key cellular processes, including proliferation, differentiation, and survival. Although NOR1 has previously been demonstrated to be required for smooth muscle cell proliferation in vitro, the role of this nuclear receptor for the proliferative response underlying neointima formation and target genes trans-activated by NOR1 remain to be defined.Using a model of guidewire-induced arterial injury, we demonstrate decreased neointima formation in NOR1(-/-) mice compared with wild-type mice. In vitro, NOR1-deficient smooth muscle cells exhibit decreased proliferation as a result of a G(1)-->S phase arrest of the cell cycle and increased apoptosis in response to serum deprivation. NOR1 deficiency alters phosphorylation of the retinoblastoma protein by preventing mitogen-induced cyclin D1 and D2 expression. Conversely, overexpression of NOR1 induces cyclin D1 expression and the transcriptional activity of the cyclin D1 promoter in transient reporter assays. Gel shift and chromatin immunoprecipitation assays identified a putative response element for NR4A receptors in the cyclin D1 promoter, to which NOR1 is recruited in response to mitogenic stimulation. Finally, we provide evidence that these observations are applicable in vivo by demonstrating decreased cyclin D1 expression during neointima formation in NOR1-deficient mice.These experiments characterize cyclin D1 as an NOR1-regulated target gene in smooth muscle cells and demonstrate that NOR1 deficiency decreases neointima formation in response to vascular injury.
Matrix metalloproteinases in lung repair
Authors: W.C. Parks
Journal: European Respiratory Journal (2003)

The aims of this article are to discuss current concepts of the function of matrix metalloproteinases (MMPs), with an emphasis on identification of authentic substrates. Focusing on matrilysin (MMP‐7), it is demonstrated how a single extracellular proteinase can regulate key and common functions of epithelial biology, namely defence against microorganisms, re-epithelialisation in response to injury and acute inflammation. Using findings from models of acute lung injury, the mechanism of matrilysin's action in these processes, that is, the proteins it acts upon to facilitate specific biological processes is discussed.

Despite their specialisation to serve distinct functions, the epithelium of different tissues respond similarly to injury and infection and regulate inflammation by equivalent mechanisms. By forming a barrier and releasing antimicrobial products, epithelia provide the first line of defence against invading pathogens. Following injury, epithelial cells initiate a programmed series of coordinated responses to restore tissue integrity. By their production of chemoattractants, adhesion molecules, and other proteins, epithelial cells recruit and confine inflammatory cells to sites of injury. Though seemingly divergent processes, the epithelial programmes regulating repair, defence and inflammation may have co-evolved, particularly with respect to the genes selectively induced. After all, injury provides an opportunity for infection, which can lead to injury; both events being proinflammatory. Hence, many of the epithelial products associated with any one of these events are likely common to all. Matrilysin (MMP‐7), is an example of a protein that functions in defence, repair, and as shown here, inflammation.

MMPs comprise a family of 23 (currently) related, yet distinct enzymes. MMPs are secreted or anchored to the cell surface 1, 2, thereby confining their catalytic activity to membrane proteins or proteins within the secretory pathway or extracellular space. As their name suggests, MMPs are thought to be responsible for the turnover and degradation of connective …
Complement bridges between cells analysis of a possible cell-cell interaction mechanism.
Authors: M P Dierich, B Landen
Journal: The Journal of Experimental Medicine (1977)

Different leukocytes (Raji, Daudi, Rael lymphoid cells; human peripheral blood lymphocytes, and guinea pig granulocytes), which had been coated with C3 by incubation of 37 degrees C for 20 min in a C3 solution, were demonstrated to form rosettes with erythrocytes coated with complement components (EAC142). The percentage of rosettes was dependent of the amount of C3 present on the cells. Loading of the lymphoid cells with C3 was a time- and temperature-dependent process. C3b was unable to serve the same purposes, although C3 and C3b occupied the C3 receptors on the lymphoid cells to a comparable degree. C3 functions in a similar manner. The C42 enzyme can be replaced by trypsin, so that bridging units may consist of C3 + C42, C5 + C42 OR C3 + trypsin, and C5 + trypsin. Bridging units can be constructed also from C4 + C1. It is suggested that enzymes on one cell liberate labile binding groups of complement components on adjacent cells, thus inducing coupling of the two cells. The possibility is raised that this type of cell interlinkage may play a role in vivo, since there is accumulating evidence that complement components are expressed in the plasma membrane of different cells.
Abstract 1987: Tumor suppressor ADAM23 mediates the HPV-associated carcinogenesis.
Authors: Paul Yang, Drake W. Williams, Terresa Kim, Ki-Hyuk Shin, Mo Kang, No-Hee Park, Reuben H. Kim
Journal: Cancer Research (2013)

Abstract “High risk” human papillomaviruses (HPV) are known to cause or are closely associated with the development of human cervical, anal and some types of head and neck cancers. Integration of HPV DNA into host genome and subsequent expression of viral oncogenes, such as E6 and E7, are critical initial events for the HPV-associated cancer development; however, HPV infection alone is not sufficient to convert normal cells to malignant phenotypes, suggesting that other additional genetic and/or epigenetic events in the HPV-infected cells are required. The aim of the current study is to identify molecular determinants that are functionally linked to the pathogenesis of the HPV-associated cancers. We used HPV-16 harboring immortalized but non-transformed oral epithelial cells (HOK-16B), infected with high-throughput Decode RNAi lentiviral screening pools containing about 70,000 shRNAmir constructs capable of knocking down the target genes individually (3-4 constructs per gene), and selected them in DMEM-based high calcium/serum media in which HOK-16B cells are not permissive to survive. From the surviving colonies, we have identified several putative tumor suppressors including A Disintegrin and etalloproteinase domain-containing protein 23 (ADAM23). The function of ADAM23 was further validated such that singly knocking down in HOK-16B cells (HOK16B/ADAM23i) acquired proliferative potential in DMEM-based medium. HOK16B/ADAM23i cells also gained resistance to ionizing radiation (IR), cisplatin treatment, and differentiation as demonstrated by colonogenic assay, MTT assay, and the 3-dimensional raft culture systems, respectively. More importantly, the expression is largely diminished in squamous cell carcinoma (SCC) cell lines but more so in HPV-harboring SCC. We further found that ADAM23 expression is high in normal human oral epithelial tissues but low or none in HPV-positive OSCC tissue specimens as determined by immunohistochemical staining. Our data suggest that ADAM23 may play a role in development of HPV-associated cancers. Citation Format: Paul Yang, Drake W. Williams, Terresa Kim, Ki-Hyuk Shin, Mo Kang, No-Hee Park, Reuben H. Kim. Tumor suppressor ADAM23 mediates the HPV-associated carcinogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1987. doi:10.1158/1538-7445.AM2013-1987
Effect Measures in Prevalence Studies
Authors: Neil Pearce
Journal: Environmental Health Perspectives (2004)

There is still considerable confusion and debate about the appropriate methods for analyzing prevalence studies, and a number of recent papers have argued that prevalence ratios are the preferred method and that prevalence odds ratios should not be used. These arguments assert that the prevalence ratio is obviously the better measure and the odds ratio is “unintelligible.” They have often been accompanied by demonstrations that when a disease is common the prevalence ratio and the prevalence odds ratio may differ substantially. However, this does not tell us which measure is the more valid to use. In fact, the prevalence odds ratio a) estimates the incidence rate ratio with fewer assumptions than are required for the prevalence ratio; b) can be estimated using the same methods as for the odds ratio in case–control studies, namely, the Mantel–Haenszel method and logistic regression; and c) provides practical, analytical, and theoretical consistency between analyses of a prevalence study and prevalence case–control analyses based on the same study population. For these reasons, the prevalence odds ratio will continue to be one of the standard methods for analyzing prevalence studies and prevalence case–control studies.
Mitral-Valve Prolapse Syndrome and Recurrent Ventricular Tachyarrhythmias
Authors: JEANNE Y. WEI
Journal: Annals of Internal Medicine (1978)

Of 60 patients referred for management of drug-refractory ventricular tachyarrhythmias, 10 (17%) had mitral-valve prolapse. These 10 patients ranged in age from 19 to 70 years (mean, 47 years); seven were women. All 10 had recurrent ventricular tachycardia, while four had a history of ventricular fibrillation. Nine patients were refractory to propranolol in combination with one or more of the standard antiarrhythmic agents. All showed improvement with aprindine therapy. The results show that refractory malignant ventricular arrhythmias may be associated with the mitral-valve prolapse syndrome; patients with mitral-valve prolapse account for a rather high percentage of those patients referred with recurrent drug-refractory ventricular tachyarrhythmias; in patients with unexplained ventricular arrhythmias, mitral-valve prolapse should be considered; and aprindine may be effective for ventricular tachyarrhythmias associated with mitral-valve prolapse.
Clinical Exercise Testing
Authors: L. Thomas Sheffield
Journal: JAMA (1982)

The authors make the point that they do not support the "arbitrary" division between cardiac stress tests and pulmonary exercise studies, since they feel that this leads to a shortsighted approach to both the measurements and their interpretation. This may be so, but it is not very common to find stress laboratory supervisors who are expert both in pulmonary disease and in cardiovascular disease. If the patient's problem happens to be that of episodic chest pain, the attending physician is likely to refer his patient for testing by someone expert in the causes of chest pain rather than to one skilled in the evaluation of lower airway resistance. This work may conveniently be considered in two sections. The first seven chapters deal with an introduction to exercise testing, the physiology of exercise, indications for testing, and stress test methodology, followed by a discussion of stress test interpretation. The remaining six
Perspectives in Leukemia
Authors: Steven O. Schwartz
Journal: JAMA (1968)

The book represents a compilation of the papers read at the Symposium of the Leukemia Society of America in December 1966. Although the primary themes are etiology and treatment, both of these subjects are approached with considerable prejudice. The viral etiology of leukemia is heavily accented as is the "total kill" approach to the treatment of acute leukemias. Some of the other areas covered are the cytogenic alterations in leukemias; immunologic factors from the etiologic, therapeutic, and prophylactic standpoints; and the kinetics of leukemic cell proliferation, both in man and the mouse. The implications of cell proliferation relative to the overall problem of leukemia are scholarly evaluated. Judging the tempo of activity in the field of leukemia research from the variety and quality of the presentations, it is obvious that the pace in the field is hectic. Which of the many approaches will in time bear fruit is difficult for
Autospecific γδ thymocytes that escape negative selection find sanctuary in the intestine
Authors: Tesu Lin, Hiroki Yoshida, Goro Matsuzaki, Sarah R. Guehler, Kikuo Nomoto, Terrence A. Barrett, Douglas R. Green
Journal: Journal of Clinical Investigation (1999)

αβ or γδ thymocytes whose T-cell receptors (TCRs) recognize endogenously expressed antigens (Ag) are autospecific and, thus, potentially self-reactive. In the thymus, such T cells are eliminated during T-cell development through a process known as negative selection. As a model of negative selection of γδ T cells, we have used G8 γδ–T cell transgenic mice, which express a γδ TCR that recognizes the nonpolymorphic MHC class I TLb molecule. Here, we demonstrate that negative selection of autospecific γδ T cells is almost complete in the adult thymus but is markedly attenuated in the neonatal thymus. A consequence of this attenuated negative selection is that potentially self-reactive γδ thymocytes are allowed to escape negative selection, undergo extrathymic differentiation, and find sanctuary in the intestinal epithelium. Interestingly, the ability of these potentially self-reactive γδ T cells to find sanctuary requires both the intestinal epithelial environment and the extrathymic presence of the self-Ag. The implications of these findings on the development and persistence of autoreactive T cells in autoimmune disease are discussed.
Activity-Dependent Modulation of Synaptic AMPA Receptor Accumulation
Authors: Richard J O’Brien, Sunjeev Kamboj, Michael D Ehlers, Kenneth R Rosen, Gerald D Fischbach, Richard L Huganir
Journal: Neuron (1998)

Both theoretical and experimental work have suggested that central neurons compensate for changes in excitatory synaptic input in order to maintain a relatively constant output. We report here that inhibition of excitatory synaptic transmission in cultured spinal neurons leads to an increase in mEPSC amplitudes, accompanied by an equivalent increase in the accumulation of AMPA receptors at synapses. Conversely, increasing excitatory synaptic activity leads to a decrease in synaptic AMPA receptors and a decline in mEPSC amplitude. The time course of this synaptic remodeling is slow, similar to the metabolic half-life of neuronal AMPA receptors. Moreover, inhibiting excitatory synaptic transmission significantly prolongs the half-life of the AMPA receptor subunit GluR1, suggesting that synaptic activity modulates the size of the mEPSC by regulating the turnover of postsynaptic AMPA receptors.
THE ADJOURNED MEETING OF THE TRUSTEES.
Authors: John B. Hamilton
Journal: JAMA (1891)

The Trustees of the Association met in Chicago on Wednesday, May 13th, all being present except Dr. Shoemaker, who was represented by proxy. The question of appointment of Editor being taken up, Dr. J. C. Culbertson, for many years editor of the<i>Lancet and Clinic</i>of Cincinnati, was placed in nomination and received the unanimous vote of the Trustees. Dr. Culbertson was also instructed to act as Business Manager. On Thursday, May 14th, the Trustees, in company with the newly elected editor, inspectedThe Journaloffice, and he was formally placed in charge. The Trustees bespeak for Dr. Culbertson the same kindly consideration that has been extended to his predecessors, and they feel sure that the results of the new management will show the wisdom of their selection. By direction of P. O. Hooper, President of the Board.
Abstract IA15: Epigenetics of hormone dependence
Authors: Myles Brown
Journal: Cancer Research (2013)

Abstract A detailed understanding of interplay between genetics and epigenetics in the progression and hormone dependence of distinct cancer subtypes is critical to the development of new approaches to prevention and therapy. Steroid hormones and their receptors play essential roles in the development and progression of both breast and prostate cancers. It remains unknown what role an epigenetically defined cell of origin plays in determining hormone responsiveness. In addition whether acquired resistance to endocrine therapy is the result of clonal evolution or the presence of hormone independent tumor-initiating cells, or both remains to be determined. Gain of function mutations and gene amplification of the androgen receptor (AR) in prostate cancer and the estrogen receptor (ER) in breast cancer in a subset of hormone refractory cases supports clonal evolution as the dominant mechanism of resistance in in these patients. We have investigated how the pathways downstream of AR and ER are activated in cases where they are not genetically altered and whether these depend on mutations in other epigenetic regulators including other transcription factors involved in steroid receptor networks and chromatin modifying enzymes involved in transcriptional regulation mediated by these receptors. Renewed success in targeting the steroid receptors themselves and promising advances in inhibiting the activity of the chromatin modifying enzymes provides new opportunities for the treatment of patients with breast and prostate cancer. Citation Format: Myles Brown. Epigenetics of hormone dependence. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr IA15.
Hemeoxygenase-1 inhibits human myometrial contractility via carbon monoxide and is upregulated by progesterone during pregnancy.
Authors: C H Acevedo, A Ahmed
Journal: Journal of Clinical Investigation (1998)

Nitric oxide was proposed as an endogenous inhibitor of myometrial contractility during pregnancy. Carbon monoxide (CO) like nitric oxide increases cGMP and is generated during the degradation of heme to biliverdin IX by hemeoxygenases (HO). Here we report that the expression of both HO-1 (inducible) and HO-2 (constitutive) were > 15-fold higher in pregnant myometrium compared to nonpregnant myometrium (n = 4, P < 0.001, P < 0.005, respectively). Moreover, the activation of the HO-CO pathway by the HO inducer, hemin (10 microM), completely inhibited spontaneous contractility (n = 3). Oxytocin-stimulated contractions (n = 5) were also significantly reduced (P < 0.05) in myometrial strips mounted for isometric recording under 2 g tension in Krebs solution. Reverse transcription-PCR analysis revealed that mRNA encoding HO-1 and HO-2 was undetected in explant cultures of nonlaboring pregnant myometrium under basal conditions, however, exposure to progesterone, but not estradiol-17beta, induced the expression of HO-1 and HO-2 mRNAs. Progesterone also significantly induced HO-1 protein synthesis (n = 4, P < 0.001) while estradiol-17beta had no effect (n = 4). In term (37-42-wk gestation) nonlaboring myometrial explants, CO production was stimulated by progesterone (10(-6) M) (n = 2) and hemin (10 microM) (n = 3) after 2 h of incubation and the effect of hemin was inhibited by 1 h of preincubation with the HO inhibitor tin protoporphyrin IX (20 microM). This study clearly demonstrates the expression of HO in the human myometrium and shows that its induction produces CO that limits uterine contractility in pregnant myometrium indicating a role for the HO-CO-cGMP pathway in the maintenance of the quiescent state of the uterus during pregnancy.
DIAGNOSIS OF HYPERPARATHYROIDISM
Authors: HEINRICH G. HAAS
Journal: Annals of Internal Medicine (1969)

Letters and Comments1 March 1969DIAGNOSIS OF HYPERPARATHYROIDISMHEINRICH G. HAAS, M.D., MAXIMILIAN A. DAMBACHER, M.D.HEINRICH G. HAAS, M.D.Search for more papers by this author, MAXIMILIAN A. DAMBACHER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-3-647_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor:In the paper "Laboratory Tests in the Diagnosis of Hyperparathyroidism in Hypercalcemic Patients" (Ann. Intern. Med. 68: 188, 1968.), Strott and Nugent reject all functional tests of primary hyperparathyroidism. However, their personal experience quoted five times is limited to eight cases, and their review of the literature is incomplete. In 1966 we published the detailed data of 29 patients with surgically proved adenomatous parathyroid disease who were compared with a similarly sized group of idiopathic renal stone formers (1). Three indexes of phosphate excretion (clearance of phosphate, tubular reabsorption of phosphate, and phosphate excretion index) and three...References1. HAAS HG: Metabolic criteria for primary hyperparathyroidism. Helv. Med. Acta 33: 91, 1966. MedlineGoogle Scholar2. KYLECANARYMINTZDE LEON LHJJDHA: Inhibitory effects of induced hypercalcemia on secretion of parathyroid hormone. J. Clin. Endocr. 22: 52, 1962. CrossrefGoogle Scholar3. BEISELGERARDBARRYHERNDONMERONEYKYLE WRESKGEGWHLH: Phosphate abnormalities in hyperparathyroidism. Metabolism 10: 771, 1961. MedlineGoogle Scholar1. KYLECANARYMINTZDELEON LHJJDHA: Inhibitory effects of induced hypercalcemia on secretion of parathyroid hormone. J. Clin. Endocr. 22: 52, 1962. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Division of Endocrinology and Metabolism Department of Medicine University Hospital (Bürgerspital) CH 4056 Basle Switzerland PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1969Volume 70, Issue 3Page: 647-648KeywordsExcretionHyperparathyroidismKidney stonesLaboratory testsParathyroidPhosphatesRenal diseases Issue Published: 1 March 1969 PDF DownloadLoading ...
Radiogallium Hot Spleen in Trousseau??s Syndrome with Splenic Vein Occlusion
Authors: HOLLEY M. DEY, MOZAFAREDDIN K. KARIMEDDINI, THOMAS E. CIESIELSKI, RICHARD P. SPENCER
Journal: Clinical Nuclear Medicine (1986)

A 75-year-old man had multiple findings that indicated thromboembolic disease. A radiocolloid study showed splenic defects. The remainder of the spleen was hot on radiogallium imaging. The patient had Trousseau's syndrome (tumor-associated thromboembolism) due to carcinoma of the pancreas. The splenic vein was obstructed. Vascular compromise should be considered in the differential diagnosis of the radiogallium hot spleen.