tbuckley/cabot-search huggingface dataset:
Glucose Metabolism After Renal Transplantation
Authors: Manfred Hecking, Alexander Kainz, Johannes Werzowa, Michael Haidinger, Dominik Döller, Andrea Tura, Angelo Karaboyas, Walter H. Hörl, Michael Wolzt, Adnan Sharif, Michael Roden, Ermanno Moro, Giovanni Pacini, Friedrich K. Port, Marcus D. Säemann
Journal: Diabetes Care (2013)

We determined prevalence, risk factors, phenotype, and pathophysiological mechanism of new-onset diabetes after transplantation (NODAT) to generate strategies for optimal pharmacological management of hyperglycemia in NODAT patients.Retrospective cohort study comparing demographics, laboratory data, and oral glucose tolerance test (OGTT)-derived metabolic parameters from kidney transplant recipients versus subjects not receiving transplants.Among 1,064 stable kidney transplant recipients (≥ 6 months posttransplantation), 113 (11%) had a history of NODAT and 132 (12%) had pretransplant diabetes. In the remaining patients, randomly assigned OGTTs showed a high prevalence of abnormal glucose metabolism (11% diabetes; 32% impaired fasting glucose, impaired glucose tolerance, or both), predominantly in older patients who received tacrolimus as the primary immunosuppressant. Compared with 1,357 nontransplant subjects, stable kidney transplant recipients had lower basal glucose, higher glycated hemoglobin, lower insulin secretion, and greater insulin sensitivity in each of the three subgroups, defined by OGTT 2-h glucose (<140, 140-199, ≥ 200 mg/dL). These findings were reinforced in linear spline interpolation models of insulin secretion and sensitivity (all P < 0.001) and in another regression model in which the estimated oral glucose insulin sensitivity index was substantially higher (by 79-112 mL/min m(2)) for transplant versus nontransplant subjects despite adjustments for age, sex, and BMI (all P < 0.001).Glucose metabolism differs substantially between kidney transplant recipients and nontransplant controls. Because impaired insulin secretion appears to be the predominant pathophysiological feature after renal transplantation, early therapeutic interventions that preserve, maintain, or improve β-cell function are potentially beneficial in this population.
Effects of laser treatment on respiratory function in malignant narrowing of the central airways.
Authors: J J Gilmartin, D Veale, B G Cooper, P M Keavey, G J Gibson, G N Morritt
Journal: Thorax (1987)

Twenty patients with inoperable carcinoma in the trachea or a main bronchus were investigated before and one and 10 days after treatment with a carbon dioxide laser. Patients were assessed by spirometry, maximum flow-volume loops, and a visual analogue score of breathlessness on a scale from 0 (not at all breathless) to 100 (very breathless). At day 10 mean FEV1 had improved from 51.9% to 62.6% of predicted (p less than 0.02) and mean peak expiratory flow (PEF) from 45.3% to 53.1% of the predicted value (p less than 0.05). Improvements in maximum inspiratory and expiratory flows at 50% vital capacity were not significant but the breathlessness score decreased from a mean of 49.1 to 35.3 (p less than 0.01). Improvements in breathlessness were significantly correlated with increases in FEV1 and PEF. Thirteen of the 20 patients had unilateral tumours with partial or complete occlusion of the main bronchus; in these perfusion and ventilation were assessed by radioisotope scans before and 10 days after treatment. Seven of the 13 patients showed an increase in perfusion of the affected lung after treatment but the improvement was small, with a mean increase in unilateral perfusion in the 13 patients of 2.4% of the total counts. Four patients with no perfusion of the affected side showed no significant improvement after laser treatment. Changes in ventilation scans were similar to those in perfusion. It is concluded that laser treatment improves airway function and dyspnoea in malignant narrowing of central airways and that in unilateral obstruction such treatment results, at best, in a small increase in the contribution of the affected lung to perfusion.
Transient restoration of anti-viral T cell responses induced by lamivudine therapy in chronic hepatitis B
Authors: Carolina Boni, Amalia Penna, Antonio Bertoletti, Vincenzo Lamonaca, Irene Rapti, Gabriele Missale, Massimo Pilli, Simona Urbani, Albertina Cavalli, Simona Cerioni, Ruggero Panebianco, Julian Jenkins, Carlo Ferrari
Journal: Journal of Hepatology (2003)
Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes.
Authors: J Tian, M A Atkinson, M Clare-Salzler, A Herschenfeld, T Forsthuber, P V Lehmann, D L Kaufman
Journal: The Journal of Experimental Medicine (1996)

We previously demonstrated that a spontaneous Th1 response against glutamate decarboxylase (GAD65) arises in NOD mice at four weeks in age and subsequently T cell autoimmunity spreads both intramolecularly and intermolecularly. Induction of passive tolerance to GAD65, through inactivation of reactive T cells before the onset of autoimmunity, prevented determinant spreading and the development of insulin-dependent diabetes mellitus (IDDM). Here, we examined whether an alternative strategy, designed to induce active tolerance via the engagement of Th2 immune responses to GAD65, before the spontaneous onset of autoimmunity, could inhibit the cascade of Th1 responses that lead to IDDM. We observed that a single intranasal administration of GAD65 peptides to 2-3-wk-old NOD mice induced high levels of IgG1 antibodies to GAD65. GAD65 peptide treated mice displayed greatly reduced IFN gamma responses and increased IL-5 responses to GAD65, confirming the diversion of the spontaneous GAD65 Th1 response toward a Th2 phenotype. Consistent with the induction of an active tolerance mechanism, splenic CD4+ (but not CD8+) T cells from GAD65 peptide-treated mice, inhibited the adoptive transfer of IDDM to NOD-scid/scid mice. This active mechanism not only inhibited the development of proliferative T cell responses to GAD65, it also limited the expansion of autoreactive T cell responses to other beta cell antigens (i.e., determinant spreading). Finally, GAD65 peptide treatment reduced insulitis and long-term IDDM incidence. Collectively, these data suggest that the nasal administration of GAD65 peptides induces a Th2 cell response that inhibits the spontaneous development of autoreactive Th1 responses and the progression of beta cell autoimmunity in NOD mice.
Differences in the birth-cohort patterns of gastric cancer and peptic ulcer
Authors: A. Sonnenberg
Journal: Gut (2010)

The aim of this epidemiological study was to follow the time trends of mortality from gastric cancer and compare them with those of gastric and duodenal ulcer.Mortality data from Denmark, England & Wales, Italy, Japan, Switzerland and the United States of the past 57-130 years were analysed. The age-specific death rates were plotted against the period of death as period-age contours and against the period of birth as cohort-age contours.The long-term time trends of gastric cancer mortality were found to rise among generations born during the 18th century until the first half of the 19th century and then decline in all subsequent generations. The rise and fall of gastric cancer preceded similar birth-cohort patterns of gastric and duodenal ulcer by about 10-30 years. With the exception of gastric cancer in the USA, similar birth-cohort phenomena were seen in all countries. In general, similar temporal patterns were also seen in men and women analysed separately.The time trends of mortality from gastric cancer are shaped by an underlying birth-cohort pattern that resembles similar patterns of peptic ulcer mortality. The occurrence of birth-cohort phenomena in gastric cancer and peptic ulcer suggests that additional secular trends besides changes in the infection with Helicobacter pylori must have contributed to the peculiar long-term behaviour of these diagnoses.
Targeting Myristoylated Alanine-Rich C Kinase Substrate Phosphorylation Site Domain in Lung Cancer. Mechanisms and Therapeutic Implications
Authors: Ching-Hsien Chen, Sarah Statt, Chun-Lung Chiu, Philip Thai, Muhammad Arif, Kenneth B. Adler, Reen Wu
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Phosphorylation of myristoylated alanine-rich C kinase substrate (phospho-MARCKS) at the phosphorylation site domain (PSD) is crucial for mucus granule secretion and cell motility, but little is known concerning its function in lung cancer.We aimed to determine if MARCKS PSD activity can serve as a therapeutic target and to elucidate the molecular basis of this potential.The clinical relevance of phospho-MARCKS was first confirmed. Next, we used genetic approaches to verify the functionality and molecular mechanism of phospho-MARCKS. Finally, cancer cells were pharmacologically inhibited for MARCKS activity and subjected to functional bioassays.We demonstrated that higher phospho-MARCKS levels were correlated with shorter overall survival of lung cancer patients. Using shRNA silencing and ectopic expression of wild-type and PSD-mutated (S159/163A) MARCKS, we showed that elevated phospho-MARCKS promoted cancer growth and erlotinib resistance. Further studies demonstrated an interaction of phosphoinositide 3-kinase with MARCKS, but not with phospho-MARCKS. Interestingly, phospho-MARCKS acted in parallel with increased phosphatidylinositol (3,4,5)-triphosphate pools and AKT activation in cells. Through treatment with a 25-mer peptide targeting the MARCKS PSD motif (MPS peptide), we were able to suppress tumor growth and metastasis in vivo, and reduced levels of phospho-MARCKS, phosphatidylinositol (3,4,5)-triphosphate, and AKT activity. This peptide also enhanced the sensitivity of lung cancer cells to erlotinib treatment, especially those with sustained activation of phosphoinositide 3-kinase/AKT signaling.These results suggest a key role for MARCKS PSD in cancer disease and provide a unique strategy for inhibiting the activity of MARCKS PSD as a treatment for lung cancer.
Isolated pulmonary resistance vessels from fetal lambs. Contractile behavior and responses to indomethacin and endothelin-1.
Authors: Y Wang, F Coceani
Journal: Circulation Research (1992)

A method was developed for recording isometric tension from isolated small arteries (mean internal diameter, 169 microns) and veins (mean internal diameter, 273 microns) of the term fetal lung and was then applied to the study of the mechanisms controlling perinatal pulmonary hemodynamics. The specific purpose was to determine whether the activity of the prostaglandin synthetic system in vessels is conditioned by the oxygen tension and the mode of action of endothelin-1. Both preparations appeared structurally intact and, after normalizing their lumen diameter to either the transmural pressure in vivo (artery) or the contractile capacity of the vessel in vitro (vein), generated force to the activating solution (5 mM Ca2+ in K+ Krebs' solution) in excess of the expected performance under physiological conditions. Treatment with indomethacin (2.8 microM) had no effect on arteries preequilibrated at low PO2 (21 +/- 1 mm Hg); however, the same treatment contracted (approximately 45% of the response to activating solution) arteries at either an intermediate (40 +/- 0.8 mm Hg) or high (70 +/- 0.9 mm Hg) PO2. Endothelin-1 contracted both arteries and veins in a concentration-dependent manner, the threshold being lower with veins (1-10 versus 10-100 pM). Endothelin-1 constriction was also seen in arteries whose tone had been raised with a thromboxane A2 analogue, whereas in thromboxane-treated veins constriction was preceded by a modest relaxation over the range of 1-1,000 pM. The findings with indomethacin lead us to infer that small pulmonary arteries are endowed with a prostaglandin-relaxing mechanism that becomes functional on raising the PO2 from fetal to neonatal levels. Endothelin-1 is a constrictor regardless of the level of intrinsic tone, suggesting a possible role of the peptide in maintaining elevated pulmonary vascular tone in the fetus.
Activation of antigen-presenting cells by microbial products breaks self tolerance and induces autoimmune disease
Authors: Hanspeter Waldner, Mary Collins, Vijay K. Kuchroo
Journal: Journal of Clinical Investigation (2004)

We describe the generation of mice that express a transgenic T cell receptor (TCR) (5B6) specific for the encephalitogenic myelin proteolipid protein (PLP) peptide 139–151, on the experimental autoimmune encephalomyelitis–resistant (EAE-resistant) B10.S background. Despite harboring a high frequency of self-reactive T cells, 5B6 transgenic mice on the B10.S background rarely develop spontaneous EAE, which is in striking contrast to 5B6 transgenic mice on the EAE-susceptible SJL background. The relative resistance to spontaneous EAE in transgenic B10.S mice is not due to deletion or anergy of T cells, but appears to be controlled by APCs. Analysis of APCs revealed a lower activation state and a lower T cell–activating capacity for APCs from B10.S mice than for those from EAE-susceptible SJL mice. When APCs in 5B6 transgenic B10.S mice were activated, for example, via TLR9 or TLR4, T cell tolerance was broken, resulting in EAE. Our findings demonstrate that activation of APCs via innate immune receptors can break self tolerance and trigger the development of autoimmunity even in a genetically resistant strain. These findings suggest that the development of autoimmune diseases such as multiple sclerosis is determined at least partly by the endogenous activation state of APCs.
Response: Re: A Prospective Study of Periodontal Disease and Pancreatic Cancer in US Male Health Professionals
Authors: D. S. Michaud
Journal: JNCI Journal of the National Cancer Institute (2007)

A Prospective Study of Periodontal Disease and Pancreatic Cancer in US Male Health ProfessionalsThe recent article by Michaud et al. ( 1 ) reported a positive association between self-reported periodontal disease and risk of pancreatic cancer in a cohort of 51 529 predominantly white US men aged 40 -75 years in the Health Professionals Follow-Up Study (HPFS).With regard to a possible chronic infection -inflammation pathway, Dr Joshipura, one of the co-authors, also demonstrated positive associations between periodontal disease and ischemic stroke ( 2 ) and peripheral arterial disease ( 3 ) in the same HPFS cohort.Because smoking is a major confounding variable that links periodontal disease and subsequent tooth loss ( 4 ) with indicators of general health, such as stroke, peripheral arterial disease, and pancreatic cancer, the authors strictly adjusted for cigarette smoking in addition to other possible confounding variables; however, they did not adjust for passive exposure to cigarette smoke.Gallicchio et al. ( 5) reported that passive exposure to cigarette smoke in the household was not associated with an increased risk of pancreatic cancer among never smokers in two cohorts that were established in Washington County, MD, noting that the confidence limits were wide due to a small number of cases (56 patients with pancreatic cancer in a cohort of 45 749 men and women and 92 in a cohort of 48 172 men and women).In that study, the authors concluded that future investigations of the associations between passive exposure to cigarette smoke and risk of pancreatic cancer should incorporate a more comprehensive measure, which should include lifetime household, occupational, and leisure time exposures to secondhand smoke.Additional adjustment for complete passive smoking exposure might reduce or eliminate the association between self-reported periodontal disease and pancreatic cancer risk as well as other general health concerns.Furthermore, it might be more helpful for the investigators to understand the periodontal disease -pancreatic cancer
The effect of prostaglandin A1 on renin and aldosterone in man.
Authors: M S Golub, P F Speckart, P K Zia, R Horton
Journal: Circulation Research (1976)

Blood pressure, pulse rate, plasma aldosterone (PA), renin, and cortisol were monitored during graded intravenous infusions of prostaglandin At (PGA)1), 0.075-0.6 mug/kg min-1, alone and superimposed on angiotensin II (A II) administration in five normal men. The infusions of PGA1 did not affect blood pressure, but did progressively increase the pulse rate up to 15.2 +/- 2.0 (SEM- beats/min at the highest prostaglandin dose (0.6 mug/kg min-1). Both PA and plasma renin activity (PRA) increased in a dose-related fashion in response to the prostaglandin infusions. Aldosterone increased from a control of 4.8 +/- 0.4 to 20.7 +/- 1.2 ng and PRA increased from 0.9 +/- 0.1 to 5.4 +/- 0.4 ng/ml hr-1 at the dose of 0.6 mug/kg min-1. The correlation between the aldosterone and renin values was r = 0.85 P less than 0.001. In separate experiments, acute volume expansion with 2 liters of saline did not affect the increase in renin activity induced by exogenous prostaglandin. A II (5 ng/kg min-1) increased aldosterone and blood pressure and decreased the pulse rate. The hemodynamic effects were progressively reversed by the superimposed prostaglandin infusions, but the observed changes in renin and aldosterone concentrations were not further altered. The PA response to A II infusions was not influenced by indomethacin pretreatment. Prostaglandin A (infusion) appears to have a direct effect on renin release in man.
Role of Rituximab Therapy in Glomerulonephritis
Authors: David Jayne
Journal: Journal of the American Society of Nephrology (2008)

B cell depletion with the monoclonal antibody rituximab is attracting increasing attention in systemic lupus erythematosus, vasculitis, and primary glomerulonephritis. Existing, uncontrolled data report high response rates in patients with refractory disease. If supported by the results of ongoing randomized trials, then rituximab and related B cell-depleting or -modulating drugs are likely to become a component in the future management of these disorders. Their use may improve patient outcomes by permitting more complete disease control and reduced exposure to glucocorticoid and traditional immunosuppressive drugs. The toxicity and infective risk of B cell-targeted agents in renal disease needs to be determined as well as their optimal dosing in combination with conventional agents.
Unequal Rates of Y Chromosome Gene Divergence during Speciation of the Family Ursidae
Authors: Shigeki Nakagome, Jill Pecon-Slattery, Ryuichi Masuda
Journal: Molecular Biology and Evolution (2008)

Evolution of the bear family Ursidae is well investigated in terms of morphological, paleontological, and genetic features. However, several phylogenetic ambiguities occur within the subfamily Ursinae (the family Ursidae excluding the giant panda and spectacled bear), which may correlate with behavioral traits of female philopatry and male-biased dispersal which form the basis of the observed matriarchal population structure in these species. In the process of bear evolution, we investigate the premise that such behavioral traits may be reflected in patterns of variation among genes with different modes of inheritance: matrilineal mitochondrial DNA (mtDNA), patrilineal Y chromosome, biparentally inherited autosomes, and the X chromosome. In the present study, we sequenced 3 Y-linked genes (3,453 bp) and 4 X-linked genes (4,960 bp) and reanalyzed previously published sequences from autosome genes (2,347 bp) in ursid species to investigate differences in evolutionary rates associated with patterns of inheritance. The results describe topological incongruence between sex-linked genes and autosome genes and between nuclear DNA and mtDNA. In more ancestral branches within the bear phylogeny, Y-linked genes evolved faster than autosome and X-linked genes, consistent with expectations based on male-driven evolution. However, this pattern changes among branches leading to each species within the lineage of Ursinae whereby the evolutionary rates of Y-linked genes have fewer than expected substitutions. This inconsistency between more recent nodes of the bear phylogeny with more ancestral nodes may reflect the influences of sex-biased dispersal as well as molecular evolutionary characteristics of the Y chromosome, and stochastic events in species natural history, and phylogeography unique to ursine bears.
Cervical Intraepithelial Neoplasia Outcomes After Treatment: Long-term Follow-up From the British Columbia Cohort Study
Authors: J. Melnikow, C. McGahan, G. F. Sawaya, T. Ehlen, A. Coldman
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundInformation on the long-term risk of cervical intraepithelial neoplasia (CIN) recurrence among women treated for CIN is limited yet critical for evidence-based surveillance recommendations.
PANHYPOPITUITARISM FOLLOWING EPIDEMIC HEMORRHAGIC FEVER. I. CLINICAL FEATURES: REPORT OF A CASE
Authors: Samuel J. Zoeckler, James A. Orbison
Journal: Annals of Internal Medicine (1955)

Case Reports1 December 1955PANHYPOPITUITARISM FOLLOWING EPIDEMIC HEMORRHAGIC FEVER. I. CLINICAL FEATURES: REPORT OF A CASESAMUEL J. ZOECKLER, JAMES A. ORBISONSAMUEL J. ZOECKLERSearch for more papers by this author, JAMES A. ORBISONSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-43-6-1316 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe late sequelae of hemorrhagic fever have not yet been completely delineated, since the opportunity for large scale follow-up study has been limited. Some of the early interest in this regard has centered around investigation of the inability of some patients to excrete a concentrated urine following apparent recovery from the acute phase of the disease. Initial consideration has been given to a residual renal defect as a responsible factor. That other factors may also be operative is suggested by our experience with a recent patient.Pathologic alterations have been reported in widespread areas of the body among patients dying...Bibliography1. HullinghorstSteer RLA: Pathology of epidemic hemorrhagic fever, Ann. Int. Med. 38: 77-101, 1953. LinkGoogle Scholar2. Lukes RJ: The pathology of thirty-nine fatal cases of epidemic hemorrhagic fever, Am. J. Med. 16: 639-650, 1954. CrossrefMedlineGoogle Scholar3. Kessler WH: Gross anatomic features found in 27 autopsies of epidemic hemorrhagic fever, Ann. Int. Med. 38: 73, 1953. LinkGoogle Scholar4. Powell GM: Hemorrhagic fever: a study of 300 cases, Medicine 33: 97-153, 1954. CrossrefMedlineGoogle Scholar5. RobinsonPowerKepler FJMHAJ: Two new procedures to assist in recognition and exclusion of Addison's disease. A preliminary report, Proc. Staff Meet., Mayo Clin. 16: 577, 1941. Google Scholar6. WahleMcKay GHD: Panhypopituitarism, following epidemic hemorrhagic fever. II. Pathologic features, to be published. Google Scholar7. FroebMcDowell HFNE: Renal function in epidemic hemorrhagic fever, Am. J. Med. 16: 671-676, 1954. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication September 24, 1954.From the Medical Service, United States Army Hospital, Fort Belvoir, Virginia. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPanhypopituitarism in the acute stage of hemorrhagic fever with renal syndrome: a case reportEndokrine und StoffwechselkrankheitenArbor-Viren (durch Arthropoden übertragbare Viren)HypophyseDas haemorrhagische Fieber KoreasDas haemorrhagische Fieber Koreas 1 December 1955Volume 43, Issue 6Page: 1316-1319KeywordsHemorrhageHemorrhagic feversMedical servicesPanhypopituitarismUrine ePublished: 1 December 2008 Issue Published: 1 December 1955 PDF downloadLoading ...