tbuckley/cabot-search huggingface dataset:
Novel tool for the study of cholecystokinin-stimulated pancreatic enzyme secretion.
Authors: H Y Gaisano, U G Klueppelberg, D I Pinon, M A Pfenning, S P Powers, L J Miller
Journal: Journal of Clinical Investigation (1989)

The molecular events that mediate cholecystokinin (CCK)-stimulated pancreatic secretion are not well defined because of the complex receptor-binding and concentration-response characteristics of this hormone. Functional models of receptor occupancy initiating the cascade leading to secretion have been complicated by the inhibition of secretion effected by supramaximal concentrations of CCK. Recent report of a CCK analogue that does not exhibit supramaximal inhibition led us to synthesize a similar analogue that could also be radiolabeled for studies of receptor binding and affinity labeling, and for studies of second messenger activity. This probe, D-Tyr-Gly-[(Nle28,31)CCK-26-32]-phenethyl ester, was a fully efficacious secretagogue with no supramaximal inhibition, and, unlike native hormone, bound to a single class of sites present on both acini and membranes. Occupation of this site correlated well with stimulation of secretion. Evidence that this was indeed a CCK-binding site were the abilities of CCK and the antagonist L-364, 718 to inhibit binding of this analogue. Affinity labeling confirmed the identity of the site mediating secretory stimulation as a Mr = 85,000-95,000 protein. Whereas the nonhydrolyzable guanosine triphosphate analogue, 5'-guanylyl-imidodiphosphate, was a potent inhibitor of CCK binding, it had no effect on binding of this secretagogue, suggesting that a novel cascade not involving a guanine nucleotide-binding protein mediates CCK stimulation of pancreatic secretion.
Antiamyloidogenic and Neuroprotective Functions of Cathepsin B: Implications for Alzheimer's Disease
Authors: Sarah Mueller-Steiner, Yungui Zhou, Hideaki Arai, Erik D. Roberson, Binggui Sun, Jennifer Chen, Xin Wang, Guiqiu Yu, Luke Esposito, Lennart Mucke, Li Gan
Journal: Neuron (2006)
Ambient C1- ions modify rat mesangial cell contraction by modulating cell inositol trisphosphate and Ca2+ via enhanced prostaglandin E2.
Authors: T Okuda, I Kojima, E Ogata, K Kurokawa
Journal: Journal of Clinical Investigation (1989)

Our recent observation showed that angiotensin II (AII) and arginine vasopressin (AVP) stimulate Ca2+-activated Cl- conductance in mesangial cells. These data raise the possibility that mesangial cell function may be modulated by extracellular chloride concentration [( Cl-]o). The present study was undertaken to test this possibility using cultured rat mesangial cells. When the [Cl-]o was reduced to zero, the percentage of mesangial cells showing contraction responding to AII and AVP was decreased from 72 +/- 9 to 33 +/- 10% and from 60 +/- 4 to 24 +/- 11%, respectively. Ca2+ transients induced by AII and AVP, measured in mesangial cells loaded with Ca2+-sensitive photoprotein aequorin, were attenuated as [Cl-]o decreased. Also, when [Cl-]o decreased, inositol trisphosphate (IP3) levels of mesangial cells were suppressed, both in the presence and absence of AII or AVP. PGE2 production by mesangial cells increased when [Cl-]o decreased and the effects of ambient Cl- deprivation could be restored by addition of indomethacin to the Cl- -free medium. Moreover, PGE2 decreased mesangial cell contractility, Ca2+ transients, and IP3 production in response to AII and AVP. These data suggest that the decrease in [Cl-]o attenuates mesangial cell contraction by suppressing IP3 production and thus Ca2+ transients in response to AII and AVP through enhanced PGE2 production.
Increase in Functional Ca <sup>2+</sup> Channels in Cerebral Smooth Muscle With Renal Hypertension
Authors: J. Marc Simard, Xing Li, Kirti Tewari
Journal: Circulation Research (1998)

Abstract —The hypothesis that availability of functional Ca 2+ channels in vascular smooth muscle is augmented in hypertension was tested in basilar artery cells from Wistar rats exhibiting stable systolic blood pressure (BP sys ) for 2 to 11 weeks after partial renal artery ligation (Goldblatt 2-kidney 1-clip [2K1C] model). Cells were freshly isolated and patch-clamped using a nystatin–perforated patch method. BP sys ranged from 110 to 280 mm Hg and correlated with normalized kidney mass. Macroscopic current-voltage curves were fit to a Boltzmann function to obtain maximum conductance (g max ), steepness and midpoint potential for the voltage dependence of activation (k and E 1/2 , respectively), and extrapolated reversal potential for the chord conductance (E rev ). Linear regression of normalized conductance (ng max =g max /cell capacitance) versus BP sys for 103 cells indicated a strong relationship, with a slope of 0.0019 nS · pF −1 · mm Hg −1 ( P &lt;0.0001). Similar analysis of data from 35 other cells exposed to 500 nmol/L Bay K 8644 gave a slope of 0.0041 nS · pF −1 · mm Hg −1 ( P =0.001). Voltage-dependent parameters, k, E 1/2 , and E rev , were not significantly related to BP sys . Single-channel measurements in cell-attached patches revealed that the number of channels in 32 patches was significantly related to BP sys ( P =0.0024) but that slope conductance, open dwell times at 0 mV, and distribution between 2 open states were not. Finally, in a subgroup of 61 cells from animals made hypertensive (180 mm Hg&lt;BP sys &lt;200 mm Hg) for ≈1/2 to 6 weeks, we found that elevation of ng max depended on duration of hypertension ( P =0.003), with no elevation at ≈1/2 week. We conclude that in the 2K1C model, availability of functional Ca 2+ channels increases with BP sys with no change in channel properties and that measurable BP sys elevation occurs before the increase in functional channels.
Complement-derived leukotactic factors in inflammatory synovial fluids of humans
Authors: Peter A. Ward, Nathan J. Zvaifler
Journal: Journal of Clinical Investigation (1971)

A large per cent of rheumatoid synovial fluids contain chemotactic activity for rabbit granulocytes (neutrophilic). The chemotactic activity is, in large part, related to the fifth (C5) and sixth (C6) components of human complement; a combination of physical-chemical techniques indicates the activity to be attributable to C567 and C5a, a cleavage product of C5. Many rheumatoid synovial fluids contain a C5-cleaving enzyme which, on the basis of substrate specificity and susceptibility to inhibitors, is very similar to an enzyme extractable from lysosomal granules of human and rabbit granulocytes. Inflammatory nonrheumatoid synovial fluids contain chemotactic activity that is related to cleavage products (C3a) of the third component of human complement (C3). Also found in these fluids is a C3-cleaving enzyme capable of producing C3a. Of the other synovial fluids examined, lupus fluids were remarkable by their total lack of chemotactic activity. These findings record for the first time the presence of complement-derived chemotactic factors in pathological human fluids.
Methylprednisolone Injections for the Carpal Tunnel Syndrome
Authors: Isam Atroshi, Magnus Flondell, Manfred Hofer, Jonas Ranstam
Journal: Annals of Internal Medicine (2013)

Steroid injections are used in idiopathic carpal tunnel syndrome (CTS), but evidence of efficacy beyond 1 month is lacking.To assess the efficacy of local methylprednisolone injections in CTS.Randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT00806871).Regional referral orthopedic department in Sweden.Patients aged 18 to 70 years with CTS but no previous steroid injections.Three groups (37 patients each) received 80 mg of methylprednisolone, 40 mg of methylprednisolone, or placebo. The patients and treating surgeons were blinded.Primary end points were the change in CTS symptom severity scores at 10 weeks (range, 1 to 5) and rate of surgery at 1 year. Three patients had missing 10-week data. All patients had 1-year data.Improvement in CTS symptom severity scores at 10 weeks was greater in patients who received 80 mg of methylprednisolone and 40 mg of methylprednisolone than in those who received placebo (difference in change from baseline, -0.64 [95% CI, -1.06 to -0.21; P = 0.003] and -0.88 [CI, -1.30 to -0.46; P < 0.001], respectively), but there were no significant differences at 1 year. The 1-year rates of surgery were 73%, 81%, and 92% in the 80-mg methylprednisolone, 40-mg methylprednisolone, and placebo groups, respectively. Compared with patients who received placebo, those who received 80 mg of methylprednisolone were less likely to have surgery (odds ratio, 0.24 [CI, 0.06 to 0.95]; P = 0.042). With time to surgery incorporated, both the 80- and 40-mg methylprednisolone groups had lower likelihood of surgery (hazard ratio, 0.46 [CI, 0.27 to 0.77; P = 0.003] and 0.57 [CI, 0.35 to 0.94; P = 0.026], respectively).The study was conducted at 1 center, and wrist splinting had previously failed for all patients.Methylprednisolone injections for CTS have significant benefits in relieving symptoms at 10 weeks and reducing the rate of surgery 1 year after treatment, but 3 out of 4 patients had surgery within 1 year.Region of Scania Research and Development Foundation and Hässleholm Hospital Organization.
Public Health Law in a New Century
Authors: Lawrence O. Gostin
Journal: JAMA (2000)

Statutes, regulations, and litigation are pivotal tools for creating conditions for people to lead healthier and safer lives. Law can educate, create incentives, and deter; mandate safer product design and use of property; and alter the informational, physical, or economic environment.This article defines public health law as the power and duty of the state to ensure conditions for people to be healthy and limitations on the state's power to constrain autonomy, privacy, liberty, and proprietary interests of individuals and businesses. The 5 essential characteristics of public health law discussed are (1) the government's responsibility to defend against health risks and promote the public's health; (2) the population-based perspective of public health, emphasizing prevention; (3) the relationship between government and the populace; (4) the mission, core functions, and services of the public health system; and (5) the power to coerce individuals, professionals, and businesses for the community's protection.
Increased Metastatic Dissemination in Human Melanoma Xenografts after Subcurative Radiation Treatment
Authors: Einar K. Rofstad, Berit Mathiesen, Kanthi Galappathi
Journal: Cancer Research (2004)

Abstract Cancer patients showing local failure after radiation treatment have increased probability for developing metastatic disease. The mechanisms behind this observation have not been identified. In the present work, metastatic spread after inadequate radiation therapy was studied by using R-18 human melanoma xenografts as models of cancer in humans. Pimonidazole was used as a hypoxia marker, and hypoxia and urokinase-type plasminogen activator receptor (uPAR) expression were detected by immunohistochemistry. R-18 tumors regrowing after subcurative irradiation showed a higher frequency of lymph node metastasis than unirradiated tumors. The expression of uPAR was up-regulated in hypoxic tumor regions, and the fractions of hypoxic and uPAR-positive cells were ∼2-fold higher in regrowing irradiated tumors than in untreated tumors. Treatment with anti-uPAR antibody blocked metastasis almost completely in irradiated as well as unirradiated tumors. The metastatic frequency was higher in tumors regrowing after irradiation than in unirradiated tumors because the irradiation induced tumor hypoxia, and tumor hypoxia induced up-regulation of uPAR.
Managing seizures in the casualty department.
Authors: P J McKee, E A Wilson, J A Dawson, J G Larkin, M J Brodie
Journal: BMJ (1990)

mg bendrofluazide daily, found fewer adverse effects in the low dose group,'5 as did a long term trial of the 5 mg dose.sWe found that the number of adverse effects in the group given 1 25 mg was the same as that in the group given placebo, although the effects were different.Patients' symptoms are known to change when they receive antihypertensive treatment.We conclude that in low doses thiazides are one of the most effective and well tolerated treatments for arterial hypertension.1 Medical Research Council Working Party on Mild to Moderate Hypertension.Adverse reactions of bcndrofluazide and propranolol for the treatment of mild hypertension.
Long-term Safety And Efficacy Of Mepolizumab For The Treatment Of Hypereosinophilic Syndrome
Authors: A.D. Klion, F.E. Roufosse, J. Kahn, G.J. Gleich, L.B. Schwartz, A. Singh, L.J. Rosenwasser, J. Denburg, J. Ring, M.E. Rothenberg, J. Sheikh, A.E. Haig, S. Mallett, D. Templeton, H. Ortega
Journal: Journal of Allergy and Clinical Immunology (2012)
Thromboplastic and Fibrinolytic Activities in Vessels of Animals
Authors: TAGE ASTRUP, KAROL BULUK
Journal: Circulation Research (1963)

Thromboplastic activity and concentration of plasminogen activator were assayed in the coats of arteries and veins from a number of species. The widely differing patterns found in these species suggest great variation in the tendency to deposit fibrin on the interior surface of the vessels. Several modes of regulating fibrin deposition after intimal injury exist in the animal organism. These observations may assist the evaluation of data obtained in experiments on animals, and they demonstrate certain limitations with respect to conclusions on pathology in man.
THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC JAUNDICE
Authors: Edward B. Krumbhaar, John H. Musser, Max M. Peet
Journal: The Journal of Experimental Medicine (1916)

1. In dogs whose splenic veins have been ligated or transplanted into the inferior vena cava, or in which an Eck fistula has been made, an anemia occurs which resembles that following splenectomy and shows the same general variation in degree and duration. 2. The resistance of the red cells to hypotonic salt solution is quickly increased, sometimes coincident with and sometimes preceding the anemia. As a rule, it gradually returns to normal in about the same length of time as it takes the anemia to disappear, but may remain increased for longer periods. 3. There is an initial leukocytosis, involving at first the polymorphonuclear leucocytes and transitional cells. As the total leukocytosis diminishes there is both a relative and actual increase of small lymphocytes and usually of eosinophils. This may either be temporary or last during the rest of the period of observation and differs from the ordinary postoperative leukocytosis. 4. Ligation of the splenic vein is followed by considerable atrophy of the spleen, but not by necrosis or thrombosis. There is rarely adequate new vein formation. The other operations cause little or no change in the spleen. 5. Whether the disturbances as described are due to the loss of a certain volume of blood to the liver, or, as has been previously suggested, to the loss of a splenic hormone, it is impossible to say. If the former is true, the method of production of the anemia still remains unexplained. It is evident, furthermore, that the latter theory has also no value unless it is assumed that this hormone must be activated by passage through the liver.
Comparison of 5-mg and 10-mg Loading Doses in Initiation of Warfarin Therapy
Authors: Linda Harrison
Journal: Annals of Internal Medicine (1997)

Loading doses of warfarin that are larger than those used for maintenance therapy are widely used in clinical practice, but they have never been prospectively evaluated.To compare the effect of 5- and 10-mg loading doses of warfarin on laboratory markers of warfarin's anticoagulant effect.Randomized clinical trial.Tertiary care teaching hospital.49 patients seen over a 5-month period with a target international normalized ratio (INR) of 2.0 to 3.0.Patients were randomly assigned to receive an initial dose of 5 or 10 mg of warfarin. Subsequent doses of warfarin were administered on the basis of dosing nomograms.INRs and levels of factors II, VII, IX, and X and protein C were measured daily for 5 days.11 of 25 patients in the 10-mg group (44% [95% CI, 34% to 54%]) and 2 of 24 patients in the 5-mg group (8% [CI, 3% to 14%]) had INRs greater than 2.0 at 36 hours (P = 0.005), at which time the factor VII levels were 27% (CI, 18% to 36%) in the 10-mg group and 54% (CI, 43% to 65%) in the 5-mg group (P < 0.001). In contrast, factor II levels were 74% (CI, 67% to 81%) in the 10-mg group and 82% (CI, 73% to 93%) in the 5-mg group (P > 0.2). At 60 hours, 9 of 25 patients in the 10-mg group (36% [CI, 17% to 54%]) and no patients in the 5-mg group had INRs greater than 3.0. At 84 hours, 15 of 24 patients in the 10-mg group (63% [CI, 43% to 81%]) and 19 of 24 patients in the 5-mg group (79% [CI, 62% to 95%]) had INRs between 2.0 and 3.0. Four patients in the 10-mg group and 1 patient in the 5-mg group received vitamin K for excessive prolongation of the INR.A 5-mg loading dose of warfarin produces less excess anticoagulation than does a 10-mg loading dose; the smaller dose also avoids the development of a potential hypercoagulable state caused by precipitous decreases in levels of protein C during the first 36 hours of warfarin therapy.
Response Classification Based on a Minimal Model of Glioblastoma Growth Is Prognostic for Clinical Outcomes and Distinguishes Progression from Pseudoprogression
Authors: Maxwell Lewis Neal, Andrew D. Trister, Sunyoung Ahn, Anne Baldock, Carly A. Bridge, Laura Guyman, Jordan Lange, Rita Sodt, Tyler Cloke, Albert Lai, Timothy F. Cloughesy, Maciej M. Mrugala, Jason K. Rockhill, Russell C. Rockne, Kristin R. Swanson
Journal: Cancer Research (2013)

Glioblastoma multiforme is the most aggressive type of primary brain tumor. Glioblastoma growth dynamics vary widely across patients, making it difficult to accurately gauge their response to treatment. We developed a model-based metric of therapy response called Days Gained that accounts for this heterogeneity. Here, we show in 63 newly diagnosed patients with glioblastoma that Days Gained scores from a simple glioblastoma growth model computed at the time of the first postradiotherapy MRI scan are prognostic for time to tumor recurrence and overall patient survival. After radiation treatment, Days Gained also distinguished patients with pseudoprogression from those with true progression. Because Days Gained scores can be easily computed with routinely available clinical imaging devices, this model offers immediate potential to be used in ongoing prospective studies.
Platelet function and simultaneous thrombelastograms from whole blood and plasma
Authors: Ion S. Jovin, Uwe Taborski, Kathrin Heidinger, Svetlana Basser, Gert Müller-Berghaus
Journal: American Journal of Hematology (1998)

lymph node involvement with rt ureter compression that required a stent insertion.Brain CT showed a suprasellar lesion involving the diencephalic and chiasmatic regions (Fig. 1a).The patient was treated with CdA (2 hr-infusion of 0.14 mg/kg die × 7 days) and Dexamethasone (0.3 mg/kg die × 4 days).Therapy was well tolerated without significant hematologic toxicity (WHO G4 leukopenia duration, 3 days; no thrombocytopenia).Partial regression of the liver, kidney, and lymph node involvement and complete regression of the brain lesions (Fig. 1b) were documented 1 month later by CT.The patient was discharged on May 24 with complete regression of the neurological symptoms.On June 13 she died from an acute cerebral vascular accident (CVA) of ischemic origin (brain CT not shown).In this patient, a single cycle of CdA induced complete regression of the brain lesion.CVA as a complication of therapy with CdA has not been reported; a relationship between treatment and the final event is unlikely.
Morita Psychotherapy: The Views from the West
Authors: HIROSHI IWAI, DAVID K. REYNOLDS
Journal: American Journal of Psychiatry (1970)

The authors discuss various Western interpretations of Morita therapy, a Japanese method of treating neurosis. They approach the divergences of opinion through five topics, including the relationship of Morita therapy with Zen Buddhism and its emphasis on bed rest and work therapy. Their conclusion is that personal and social background and research setting influence differing understandings of Morita therapy.
Telephone Medicine: A Guide for the Practicing Physician
Authors: Bryce Templeton
Journal: Annals of Internal Medicine (2002)

Medical Writings: Book Notes2 July 2002Telephone Medicine: A Guide for the Practicing PhysicianBryce Templeton, MD, MEd, MCPBryce Templeton, MD, MEd, MCPHahnemann School of Medicine, Philadelphia, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-137-1-200207020-00034 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Reisman AB, Stevens DL, eds. 429 pages. Philadelphia: American Coll of Physicians; 2002. $40.00. ISBN 0943126878. Order phone 800-523-1546, ext. 2600.Field of medicine: Medical interviewing.Format: Softcover book.Audience: Primary care physicians who wish to enhance their ability to communicate with patients by telephone.Purpose: To improve the practice-related telephone skills of primary care physicians.Content: Thirteen chapters are devoted to the screening of patients with common problems, such as chest pain, abdominal pain, sore throat, headache, domestic violence, and depression and suicidality. Other chapters cover the process of communicating on the telephone, approaches in dealing with difficult patients, ... Author, Article, and Disclosure InformationAffiliations: Hahnemann School of Medicine, Philadelphia, Pennsylvania. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 2 July 2002Volume 137, Issue 1Page: 76KeywordsAlgorithmsDomestic violenceEvidence based medicineFallsHeadachesIschemiaMedical educationPharyngitisPrimary care physiciansSoftware tools ePublished: 2 July 2002 Issue Published: 2 July 2002 Copyright & PermissionsCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...