tbuckley/cabot-search huggingface dataset:
Constitutively Activated Receptors for Parathyroid Hormone and Parathyroid Hormone–Related Peptide in Jansen's Metaphyseal Chondrodysplasia
Authors: E. Schipani, C.B. Langman, A.M. Parfitt, G.S. Jensen, S. Kikuchi, S.W. Kooh, W.G. Cole, H. Jüppner
Journal: New England Journal of Medicine (1996)

An activating mutation of the receptor for parathyroid hormone (PTH) and parathyroid hormone–related peptide (PTHrP) was recently found in a patient with Jansen's metaphyseal chondrodysplasia, a rare form of short-limbed dwarfism associated with hypercalcemia and normal or low serum concentrations of the two hormones. To investigate this and other activating mutations and to refine the classification of this unusual disorder, we analyzed genomic DNA from six additional patients with Jansen's disease.
JUNB/AP-1 controls IFN-γ during inflammatory liver disease
Authors: Martin K. Thomsen, Latifa Bakiri, Sebastian C. Hasenfuss, Rainer Hamacher, Lola Martinez, Erwin F. Wagner
Journal: Journal of Clinical Investigation (2013)

Understanding the molecular pathogenesis of inflammatory liver disease is essential to design efficient therapeutic approaches. In hepatocytes, the dimeric transcription factor c-JUN/AP-1 is a major mediator of cell survival during hepatitis, although functions for other JUN proteins in liver disease are less defined. Here, we found that JUNB was specifically expressed in human and murine immune cells during acute liver injury. We analyzed the molecular function of JUNB in experimental models of hepatitis, including administration of concanavalin A (ConA) or α-galactosyl-ceramide, which induce liver inflammation and injury. Mice specifically lacking JUNB in hepatocytes displayed a mild increase in ConA-induced liver damage. However, targeted deletion of Junb in immune cells and hepatocytes protected against hepatitis in experimental models that involved NK/NKT cells. The absence of JUNB in immune cells decreased IFN-γ expression and secretion from NK and NKT cells, leading to reduced STAT1 pathway activation. Systemic IFN-γ treatment or adenovirus-based IRF1 delivery to Junb-deficient mice restored hepatotoxicity, and we demonstrate that Ifng is a direct transcriptional target of JUNB. These findings demonstrate that JUNB/AP-1 promotes cell death during acute hepatitis by regulating IFN-γ production in NK and NKT cells and thus functionally antagonizes the hepatoprotective function of c-JUN/AP-1 in hepatocytes.
Ethics and Epidemiology
Authors: Abraham B. Bergman
Journal: JAMA (1996)

My initial thought on seeing this book was to wonder how epidemiologists came to be involved in ethical issues. Whereas ethics involves the interactions of live souls, I thought, epidemiologists concern themselves with figures, computer printouts, and statistical tests. Not so. The editors, Steven Coughlin, an epidemiologist, and Tom Beauchamp, a philosopher, state in the preface, "... epidemiologists have professional obligations both to advance scientific knowledge<i>and</i>[emphasis mine] to enhance, protect, and restore public health through the application of this knowledge. [They] must plan and conduct studies that involve live subjects, analyze the results, and, an increasingly tricky part, explain their implications." In this book, 18 contributors from the fields of epidemiology, ethics, and law examine "how knowledge is acquired, and how moral judgments are made regarding the acquisition and use of knowledge." The chapters are divided among five sections: "Foundations," "Informed Consent, Privacy and Confidentiality," "Balancing Risks and Benefits,"
Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen).
Authors: L L Lanier, T J Kipps, J H Phillips
Journal: The Journal of Experimental Medicine (1985)

A subset of peripheral blood T lymphocytes coexpressing CD3 and IgG Fc receptors (FcR) (CD16/Leu-11 antigen) have been identified, isolated, and functionally characterized. The CD3+, CD16+ cells were established in short-term culture using growth medium containing interleukin 2 (IL-2). Both the freshly isolated cells and the cultured cell line stably expressed the CD3+, CD16+ phenotype. Furthermore, a majority of these T cells lacked either CD4 or CD8 expression. Like in vitro-activated cytotoxic T lymphocytes and natural killer (NK) cells, the CD3+, CD16+ cells showed numerous azurophilic granules. Although these cells failed to mediate significant levels of NK cell-mediated cytotoxicity even after stimulation with IL-2, they efficiently functioned as effectors of antibody-dependent cellular cytotoxicity (ADCC). The Ig isotype specificity of the ADCC was analyzed using an isotype switch-variant family of a murine anti-HLA monoclonal antibody (mAb). Similar to the CD3-, CD16+ NK cell population, the CD3+, CD16+ T cells preferentially used the IgG2a antibody to mediate ADCC. The CD3+, CD16+ cells demonstrated a proliferative response when cocultured with either a NK-sensitive tumor cell line, K562, or a NK-insensitive B lymphoblastoid cell line, CCRF-SB. The response against CCRF-SB was significantly inhibited by anti-IL-2 receptor antibody, whereas the response against K562 was only partially diminished. Cytotoxicity was also induced in the CD3+, CD16+ population by the presence of anti-CD3 mAb, indicating that cytotoxicity can be triggered by stimulation via the CD3-T cell antigen receptor complex. By isolating these CD3+, CD16+ cells from the peripheral blood of a normal, healthy individual, it has been possible to extensively study the morphology, antigenic phenotype, and functional behavior of this unique subset of T lymphocytes expressing IgG FcR.
Democracy-Independence Trade-Off in Oscillating Dendrites and Its Implications for Grid Cells
Authors: Michiel W.H. Remme, Máté Lengyel, Boris S. Gutkin
Journal: Neuron (2010)

Dendritic democracy and independence have been characterized for near-instantaneous processing of synaptic inputs. However, a wide class of neuronal computations requires input integration on long timescales. As a paradigmatic example, entorhinal grid fields have been thought to be generated by the democratic summation of independent dendritic oscillations performing direction-selective path integration. We analyzed how multiple dendritic oscillators embedded in the same neuron integrate inputs separately and determine somatic membrane voltage jointly. We found that the interaction of dendritic oscillations leads to phase locking, which sets an upper limit on the timescale for independent input integration. Factors that increase this timescale also decrease the influence that the dendritic oscillations exert on somatic voltage. In entorhinal stellate cells, interdendritic coupling dominates and causes these cells to act as single oscillators. Our results suggest a fundamental trade-off between local and global processing in dendritic trees integrating ongoing signals.
Progress on new vaccine strategies against chronic viral infections
Authors: Jay A. Berzofsky, Jeffrey D. Ahlers, John Janik, John Morris, SangKon Oh, Masaki Terabe, Igor M. Belyakov
Journal: Journal of Clinical Investigation (2004)

Among the most cost-effective strategies for preventing viral infections, vaccines have proven effective primarily against viruses causing acute, self-limited infections. For these it has been sufficient for the vaccine to mimic the natural virus. However, viruses causing chronic infection do not elicit an immune response sufficient to clear the infection and, as a result, vaccines for these viruses must elicit more effective responses — quantitative and qualitative — than does the natural virus. Here we examine the immunologic and virologic basis for vaccines against three such viruses, HIV, hepatitis C virus, and human papillomavirus, and review progress in clinical trials to date. We also explore novel strategies for increasing the immunogenicity and efficacy of vaccines.
Carbachol- and elevated Ca(2+)-induced translocation of functionally active protein kinase C to the brush border of rabbit ileal Na+ absorbing cells.
Authors: M E Cohen, J Wesolek, J McCullen, K Rys-Sikora, S Pandol, R P Rood, G W Sharp, M Donowitz
Journal: Journal of Clinical Investigation (1991)

Protein kinase C is involved in mediating the effects of elevated Ca2+ in ileal villus Na+ absorbing cells to inhibit NaCl absorption. The present studies were undertaken to understand the mechanism by which this occurs. The effects of carbachol and the calcium ionophore A23187, agents which elevate intracellular Ca2+ and inhibit NaCl absorption in ileal villus cells, were studied. Carbachol treatment of villus cells caused a rapid decrease in protein kinase C activity in cytosol, with an accompanying increase in microvillus membrane C kinase. Exposure of the villus cells to calcium ionophore also caused a quantitatively similar decrease in cytosol C kinase and increase in C kinase activity in the microvillus membrane. This increase caused by carbachol and Ca2+ ionophore was specific for the microvillus membrane. In fact, 30 s and 10 min after exposure of the cells to carbachol, basolateral membrane protein kinase C decreased, in a time-dependent manner; whereas 10 min of Ca2+ ionophore exposure did not alter basolateral C kinase. Exposure of villus cells to Ca2+ ionophore or carbachol caused similar increases in microvillus membrane diacylglycerol content. As judged by the ability to inhibit Na+/H+ exchange measured in ileal villus cell brush border membrane vesicles, the protein kinase C which translocated to the microvillus membrane was functionally significant. Inhibition of Na+/H+ exchange required ATP and was reversed by the protein kinase C antagonist H-7. In conclusion, the effect of carbachol and Ca2+ ionophore in regulation of ileal NaCl absorption is associated with an increase in microvillus membrane diacylglycerol content and functionally active protein kinase C. The effects of both carbachol and Ca2+ ionophore are different on brush border and basolateral membrane distribution of protein kinase C.
Test Performance of Positron Emission Tomography and Computed Tomography for Mediastinal Staging in Patients with Non–Small-Cell Lung Cancer
Authors: Michael K. Gould, Ware G. Kuschner, Chara E. Rydzak, Courtney C. Maclean, Anita N. Demas, Hidenobu Shigemitsu, Jo Kay Chan, Douglas K. Owens
Journal: Annals of Internal Medicine (2003)

Purpose: To compare the diagnostic accuracy of computed tomography (CT) and positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) for mediastinal staging in patients with non–small-cell lung cancer and to determine whether test results are conditionally dependent (the sensitivity and specificity of FDG-PET depend on the presence or absence of enlarged mediastinal lymph nodes on CT). Data Sources: Computerized search of MEDLINE, EMBASE, BIOSIS, and CancerLit through March 2003 and reference lists of retrieved studies and review articles. Study Selection: Studies in any language that examined FDG-PET for mediastinal staging in patients with known or suspected non–small-cell lung cancer, enrolled at least 10 participants (including at least 5 participants with mediastinal metastasis), and provided enough data to permit calculation of sensitivity and specificity for identifying lymph node involvement. Data Extraction: One reviewer (of non-English-language studies) or 2 reviewers (of English-language studies) independently evaluated studies for inclusion, rated methodologic quality, and abstracted relevant data. Data Synthesis: Thirty-nine studies met inclusion criteria. Methodologic quality varied, but few aspects of study quality affected diagnostic accuracy. The authors constructed summary receiver-operating characteristic curves for CT and FDG-PET. Positron emission tomography with 18-fluorodeoxyglucose was more accurate than CT for identifying lymph node involvement (P < 0.001). For CT, median sensitivity and specificity were 61% (interquartile range, 50% to 71%) and 79% (interquartile range, 66% to 89%), respectively. For FDG-PET, median sensitivity and specificity were 85% (interquartile range, 67% to 91%) and 90% (interquartile range, 82% to 96%), respectively. Fourteen studies provided information about the conditional test performance of CT and FDG-PET. Positron emission tomography with 18-fluorodeoxyglucose was more sensitive but less specific when CT showed enlarged lymph nodes (median sensitivity, 100% [interquartile range, 90% to 100%]; median specificity, 78% [interquartile range, 68% to 100%]) than when CT showed no lymph node enlargement (median sensitivity, 82% [interquartile range, 65% to 100%]; median specificity, 93% [interquartile range, 92% to 100%]; P = 0.002). Conclusions: Positron emission tomography with 18-fluorodeoxyglucose is more accurate than CT for mediastinal staging. Positron emission tomography with 18-fluorodeoxyglucose is more sensitive but less specific when CT shows enlarged mediastinal lymph nodes.
I alpha-hydroxycholecalciferol: a treatment of renal bone disease.
Authors: G R Catto, M MacLeod, B Pelc, E Kodicek
Journal: BMJ (1975)

Three patients with chronic renal failure on maintenance haemodialysis have been treated with 1 alpha-hydroxycholecalciferol (1 alpha-OHCC), a synthetic vitamin D analogue. A daily dose of 2 mug by mouth produced a significant increase in both calcium absorption from the gastrointestinal tract and calcium content of bone. Treatment with 1 alpha-OHCC appears to be effective in cases of metabolic bone disease associated with chronic renal failure.
Inositol 1,4,5-trisphosphate may regulate rat brain Cai++ by inhibiting membrane bound Na(+)-Ca++ exchanger.
Authors: C L Fraser, P Sarnacki
Journal: Journal of Clinical Investigation (1990)

The role of inositol 1,4,5-trisphosphate (1,4,5-IP3) in regulating cytosolic Ca++ by stimulating Ca++ release from intracellular organelles is well established. However, other modes of intracellular Ca++ regulation by 1,4,5-IP3 have not been determined. To determine if 1,4,5-IP3 may regulate cell cytosolic Ca++ by acting on plasma membrane bound Na(+)-Ca++ exchanger, we investigated Ca++ transport in synaptosomes using 45Ca++ as tracer. In the presence of either an inhibitor of voltage gated Na+ channels (tetrodotoxin) or the K+ ionophore (valinomycin), Ca++ uptake was significantly inhibited (P less than 0.05) by 1,4,5-IP3 in a concentration dependent manner, with half-maximal inhibition occurring at submicromolar concentrations between 10(-9) M and 10(-10) M 1,4,5-IP3. Similarly, Ca++ efflux by the exchanger was significantly inhibited 40% by 1,4,5-IP3. The inhibitory effect of 1,4,5-IP3 on the Na(+)-Ca++ exchanger was observed in the presence of Ca++ channel blockers, and in vesicles pretreated with caffeine to deplete the 1,4,5-IP3-sensitive stores of Ca++. These results suggest that during signal transduction in brain, 1,4,5-IP3 may increase cytosolic [Ca++] in part by inhibiting the Na(+)-Ca++ exchanger and thus, Ca++ efflux from cell.
Screening for hereditary haemochromatosis should be implemented now
Authors: K. Allen
Journal: BMJ (2000)

EDITOR—The editorial by Haddow and Bradley on population screening for haemochromatosis concludes that now is too early to start population screening because of uncertainties about the proportion of homozygotes who will express symptoms of the disease.1 Haemochromatosis has been recognised as a clinical entity for over 150 years, but the gene that is mutated was not identified until 1996. Clinical haemochromatosis, defined by the presence of abnormal serum iron variables, has consistently been estimated to affect …
Clinical and Biochemical Studies of Families of Schizophrenic Patients
Authors: THOMAS M. SULLIVAN, CHARLES E. FROHMAN, PETER G. S. BECKETT, JACQUES S. GOTTLIEB
Journal: American Journal of Psychiatry (1967)

Previous studies from the Lafayette Clinic have reported a protein factor, identified by the L/P ratio, found in significantly greater concentration in the plasma of chronic schizophrenic patients than in that of some control subjects. Other schizophrenic patients clinically very similar do not have the factor. Family members of high-factor patients were more likely to have elevated L/P ratios than were family members of low-factor patients. In this study, 117 family members of the patients were seen for psychiatric evaluation and psychological testing. In these family members schizophrenic symptomatology was not found to correlate with elevation of the L/P ratio. The authors conclude that the protein factor is not directly related to clinical manifestations of schizophrenia.
Prior-Authorization Programs for Controlling Drug Spending
Authors: Mary Beth Hamel, Arnold M. Epstein
Journal: New England Journal of Medicine (2004)

Spending for prescription drugs represents more than 10 percent of the nation's health care costs and is currently the fastest-growing component of health care expenditures.1 The rapid increase in drug spending has resulted from the expansion of the volume of medications prescribed, as well as a shift toward the inclusion of more new and expensive drugs. Medicaid programs have been especially vulnerable to the skyrocketing spending on drugs, which has often exacerbated state budget woes. Increasing at more than twice the rate of overall Medicaid spending, Medicaid expenditures for prescription drugs rose 18 percent annually between 1997 and 2000.2 Medicaid . . .
Altered fibrin clot structure/function in patients with idiopathic venous thromboembolism and in their relatives
Authors: Anetta Undas, Krystyna Zawilska, Mariola Ciesla-Dul, Agata Lehmann-Kopydłowska, Agnieszka Skubiszak, Katarzyna Ciepłuch, Wiesława Tracz
Journal: Blood (2009)
Instruments in the Assessment of Psychosomatic and Neurotic Disorders
Authors: Rolf-Dieter Stieglitz, Gerhard Schüssler
Journal: Psychotherapy and Psychosomatics (1995)

The introduction of DSM-III/DSM-III-R and ICD-10 implies fundamental innovations to the diagnostic process. The changes relate both to formal aspects (e.g. symptom and time-related criteria) and to content (e.g. the abandonment of the concept of neurosis). Additionally, specific assessment instruments are introduced. However, other aspects important for the description and treatment of patients easily become neglected when concentrating on a system of diagnoses which aim at the classification of patients by groups of disorders. The present article will present instruments which make it possible to do justice to both points of view.
Major parietal cell antigen in autoimmune gastritis with pernicious anemia is the acid-producing H+,K+-adenosine triphosphatase of the stomach.
Authors: F A Karlsson, P Burman, L Lööf, S Mårdh
Journal: Journal of Clinical Investigation (1988)

In autoimmune gastritis antibodies against a membrane-bound parietal cell antigen of previously unknown function are present in the sera of patients. In this study, a vesicular membrane preparation of porcine gastric mucosa cells was found to be a potent antigenic source. This preparation blocked greater than 90% of antibody binding to a lysate of gastric mucosa cells. The membrane fraction contained H+,K+-ATPase (EC 3.6.1.36) as the major protein, which in sodium dodecyl sulfate-polyacrylamide gel electrophoresis migrated with a weight of 92 kD. After reduction and alkylation, this component was resolved into two bands of similar staining intensity (92 and 88 kD). Immunoblotting analysis showed that sera of patients recognized antigen with pattern identical to the major protein of the vesicular membranes. Protein A-Sepharose beads preincubated with immunoglobulins of five individual patient (but not control) sera were all found to reduce both the H+,K+-ATPase activity and the amount of parietal cell antigen of a preparation of vesicular membranes solubilized in n-octylglucoside. Taken together, the results of this study indicate that the major parietal cell antigen is identical to the acid-producing enzyme, H+,K+-ATPase, of the parietal cell.
Decrease of ischemic injury to the isolated perfused rat liver by loop diuretics
Authors: R J Fiegen, U Rauen, M Hartmann, U K Decking, H de Groot
Journal: Hepatology (1997)

Recent studies suggest a major role played by sodium in the pathogenesis of ischemic liver injury: in these studies, sodium-free media have been shown to offer protection against hypoxic injury to isolated hepatocytes. As sodium-free perfusions of the isolated rat liver proved impossible because of extensive vasoconstriction, we assessed the effects of two inhibitors of the Na + -K + -2Cl - cotransporter, the loop diuretics furosemide and bumetanide, on ischemic liver injury. In untreated control livers lactate dehydrogenase (LDH) efflux immediately after reperfusion after 60 minutes of ischemia at 37 degrees C was 1666 ± 473 U/L. When livers were pretreated with furosemide or bumetanide before the ischemic period, LDH efflux was only 773 ± 292 U/L and 702 ± 183 U/L respectively ( P &lt; .01). LDH activity in the effluent of the pretreated livers remained significantly below the values of ischemic control livers for the whole reperfusion period of 90 minutes. Bile flow in the postischemic phase was improved by pretreatment with furosemide or bumetanide. The increase in intracellular sodium, as measured by 23Na-NMR, was attenuated from 193% ± 71% during 60 minutes of ischemia in controls to 148% ± 80% after bumetanide application ( P &lt; .05). Also, after 120 minutes of warm ischemia, LDH and aspartate aminotransferase release were significantly decreased and bile flow increased by pretreatment with bumetanide. Thus, both furosemide and bumetanide showed a clear benificial effect on rat livers subjected to warm ischemia. These data suggest that one means by which sodium ions are accumulated during liver ischemia might be the Na + -K + -2Cl - cotransporter, which is blocked by furosemide and bumetanide.