tbuckley/cabot-search huggingface dataset:
The therapeutic Smartie.
Authors: J M Simpson
Journal: BMJ (1978)

We studied how similar postsynaptic responses are maintained in the face of interindividual variability in the number of presynaptic neurons. In the stomatogastric ganglion of the lobster, <i>Homarus americanus</i>, the pyloric (PY) neurons exist in variable numbers across animals. We show that each individual fiber of the stomach muscles innervated by PY neurons received synaptic input from all neurons present. We performed intracellular recordings of excitatory junction potentials (EJPs) in the muscle fibers to determine the consequences of differences in the number of motor neurons. Despite the variability in neuron number, the compound electrical response of muscle fibers to natural bursting input was similar across individuals. The similarity of total synaptic activation was not due to differences in the spiking activity of individual motor neurons across animals with different numbers of PY neurons. The amplitude of a unitary EJP in response to a single spike in a single motor neuron also did not depend on the number of PY neurons present. Consequently, the compound EJP in response to a single stimulus that activated all motor axons present was larger in individuals with more PY neurons. However, when axons were stimulated with trains of pulses mimicking bursting activity, EJPs facilitated more in individuals with fewer PY neurons. After a few stimuli, this resulted in depolarizations similar to the ones in individuals with more PY neurons. We interpret our findings as evidence that compensatory or homeostatic regulatory mechanisms can act on short-term synaptic dynamics instead of absolute synaptic strength.
A Surprising Advance in the Treatment of Viral Leukemia
Authors: Robert C. Gallo
Journal: New England Journal of Medicine (1995)

Leukemia can be acute or chronic, derive from different types of cells, and arise by different mechanisms, most of which are still unknown. One unique form — adult T-cell leukemia–lymphoma — though rare in many geographic regions, is common in others. It is perhaps the most thoroughly studied type of leukemia. We know more about its distribution, cause, and pathogenesis than we do about those of other leukemias,16 but paradoxically, it remains one of the most difficult cancers to treat.4 Two reports in this issue of the Journal may herald a change in that situation.7,8 In 1977 Takatsuki . . .
Dose-related reversal of acute lung rejection by aerosolized cyclosporine.
Authors: A T Iacono, G C Smaldone, R J Keenan, P Diot, J H Dauber, A Zeevi, G J Burckart, B P Griffith
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

This study evaluated the effectiveness of aerosolized cyclosporine as rescue therapy for refractory acute rejection in lung-transplant patients that is unresponsive to conventional therapy. Over 2 yr, nine allograft recipients with histologic evidence of persistent acute rejection and worsening pulmonary function were enrolled. Twenty-two patients with similar degrees of unremitting rejection served as historical controls. Aerosolization of cyclosporin A (300 mg in 4.8 ml propylene glycol) using an AeroTech II jet nebulizer was instituted daily for 12 consecutive days followed by a maintenance regimen of 3 d/wk. Cyclosporine and tacrolimus blood and plasma levels were maintained within therapeutic ranges throughout this trial. Efficacy was assessed by histologic grade of rejection, interleukin-6 (IL-6) mRNA expression by graft bronchoalveolar lavage cells, and pulmonary function testing before and during cyclosporine therapy. In seven patients, results were correlated to deposition of cyclosporine aerosol in the allograft(s) as measured by radioisotopic techniques. At a mean of 37 d after initiation of aerosolized cyclosporine, graft histology improved in eight of the nine patients. Cellular IL-6 mRNA expression decreased significantly in seven patients (mean IL-6/actin +/- SD, 40.96 +/- 118 versus 0.33 +/- 0.57 [p = 0.038]). Pulmonary function (FEV1), which had decreased posttransplant (over a mean of 347 d of observation) from a best value of 1.98 +/- 0.8 L to 1.59 +/- 0.6 L (p = 0.0077), improved over time (152 d) to a posttransplant value of 1.90 +/- 0.8 (p = 0.025). In the control subjects, FEV1 inexorably declined over a comparable period of observation (best posttransplant value 2.36 +/- 0.86 to 1.32 +/- 0.53, p < 0.0001). There was a strong correlation between cyclosporine deposition in the allograft and improvement in FEV1 (r = 0.900, p < 0.01). Fewer cycles of pulsed corticosteroids (1.4 +/- 0.9 versus 0.2 +/- 0.4, p = 0.011) and anti-thymocyte globulin 0.8 +/- 0.4 versus 0, p = 0.018) and reduced doses of oral prednisone (10.8 +/- 3.1 versus 6.1 +/- 4.2 mg/d, p = 0.026) were observed during treatment with aerosolized cyclosporine. Episodes of pneumonia also were reduced significantly during aerosol therapy (2.6 versus 0.95 episodes/100 d, p = 0.029). Nephrotoxicity and hepatotoxicity did not occur, and no patients withdrew from the study. Aerosolized cyclosporine appears to be safe and effective therapy for refractory acute rejection, but confirmation by a larger, randomized trial is necessary. The correlation observed between deposition of cyclosporine aerosol and physiologic improvement of lung function suggests that there is a dose-response relationship between the concentration of cyclosporine in the allograft and immunologic tolerance.
Serial immunologic identification of lymphocyte subsets in murine coxsackievirus B3 myocarditis: different kinetics and significance of lymphocyte subsets in the heart and in peripheral blood.
Authors: C Kishimoto, T Misaki, C S Crumpacker, W H Abelmann
Journal: Circulation (1988)

To elucidate possible immune mechanisms in the pathogenesis of myocarditis, we examined, by immunofluorescence techniques, the serial changes in lymphocyte subsets in the heart, spleen, and peripheral blood of C3H/He mice inoculated coxsackievirus B3 (experiment I). B cells were identified by staining with fluorescein isothiocyanate-labeled rabbit antimouse immunoglobulin. T cell subsets were demonstrated with rat anti-Thy 1.2, anti-Lyt 1, anti-Lyt 2, and anti-L3T4 monoclonal antibodies, respectively, plus fluorescein isothiocyanate-labeled antimouse immunoglobin. The percent of Thy 1.2+, Lyt 1+, and L3T4+ cells was decreased in the peripheral blood on days 3, 7, and 14. B cells were increased on day 3. In contrast, Thy 1.2+ (pan T) or Lyt 1+ cells appeared to occupy the major portion of the myocardium on days 7 and 14, when myocarditis was most severe, while B cells were sparse. For confirmation, serial immunohistologic studies (immunoperoxidase staining) of the hearts of C3H/He mice with coxsackievirus B3 myocarditis were performed (experiment II). Most of the stained cells in the heart were Thy 1.2, Lyt 1, and Lyt 2 positive on days 7 and 14. Thus, independent methods demonstrate that specific antigenic markers on lymphocytes at the site of inflammation in the acute stage of viral myocarditis differ from those on corresponding peripheral lymphocytes, and suggest the possible involvement of Thy 1.2+ (pan T) cells, mainly the Lyt 1+ and Lyt 2+ subsets (immature T cells), in the development of myocarditis in this preparation.
Diclofenac Sodium and Bruising
Authors: Uri Khazan
Journal: Annals of Internal Medicine (1990)

Letters and Corrections15 March 1990Diclofenac Sodium and BruisingUri Khazan, MD, Mary Toth, MD, Anand Mutgi, MDUri Khazan, MDSearch for more papers by this author, Mary Toth, MDSearch for more papers by this author, Anand Mutgi, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-3-112-6-472_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: No reports to date have described prolonged bleeding time and spontaneous bruising with the use of diclofenac sodium. A literature search (Index Medicus and Excerpta Medica) revealed a single study that described reversible inhibition of platelet aggregation without prolongation of bleeding time with the use of diclofenac sodium (1). Moreover, the manufacturer (Geigy) reports no effect on bleeding time with its use (2). We report a case of spontaneous bruising and prolongation of bleeding time temporally associated with the use of diclofenac sodium.An otherwise healthy 45-year-old woman complained of spontaneous bruising for 1 week. She denied...References1. FrancisDawsRoath JRO. The effect of diclofenac on platelet aggregation and post-operative bleeding. Hematol Rev Commun. 1988;2/3:283-91. Google Scholar2. Physicians' Desk Reference. 43d ed. Oradel, New Jersey: Medical Economics Company; 1989:984-5. Google Scholar3. NadelBrunoVarady JJE. Effect of naproxen and of aspirin on bleeding time and platelet aggregation. J Clin Pharmacol. 1974;14:1975-82. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Medical College of Ohio Toledo, OH 43699 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDiclofenacThe rate of fibrinopeptide B release modulates the rate of clot formation: a study with an acquired inhibitor to fibrinopeptide B releaseThe Clinical Importance of Acquired Abnormalities of Platelet FunctionAnti-inflammatory analgesics and drugs used in rheumatoid arthritis and gout 15 March 1990Volume 112, Issue 6Page: 472-473KeywordsHemorrhagePlatelet aggregationSodium Issue Published: 15 March 1990 PDF DownloadLoading ...
Generation of T cells with lytic specificity for atypical antigens. II. A novel antigen system in the rat dependent on homozygous expression of major histocompatibility complex genes of the class I-like RT1C region.
Authors: J D Davies, D H Wilson, G W Butcher, D B Wilson
Journal: The Journal of Experimental Medicine (1991)

Lymphocytes from parental strain DA rats can induce potent killer cell responses to atypical antigen systems in F1 Lewis (L)/DA and DA/L recipients. Here, we describe an antigen system, H, present on homozygous parental target cells, but not on F1 cells. This antigen system is unusual in several respects: it does not involve class I RT1A gene products usually used by killer cell responses in the rat, it maps to the major histocompatibility complex (MHC) class I-like RT1C region, and it requires homozygous expression of RT1Cav1 alleles. This may be another example, this time involving the RT1C region, of an MHC gene product antigenically altered by an MHC-linked trans-activating modifier gene.
Cost Containment and Coronary Artery Surgery
Authors: Richard H. Egdahl
Journal: JAMA (1983)

Loop and co-workers, in this issue ofThe Journal(p 63), describe studies in which they have been able to achieve major savings for patients undergoing coronary artery bypass graft (CABG) by a reassessment of the entire operative experience. By carrying out workups on an outpatient basis and admitting patients on the day of surgery, by decreasing special care unit time by one day, by not performing routine blood cross-match, and by not using preoperative Swan-Ganz catheters in uncomplicated cases, they have documented unit cost savings for their patients. By contrasting the group of Cleveland Clinic patients who were admitted on the day of surgery with another group with the usual two preoperative days in the hospital, they show that at least $1,000 per case has been saved in 1977 constant dollars. This work confirms and extends the 1979 study of Tomatis et al,<sup>1</sup>who demonstrated for CABG in
Early Diagnosis of Cancer of the Cervix Uteri
Authors: M. Donaldson
Journal: BMJ (1955)

Three Important Questions Questions that arise are: (1) Does the delay that takes place between noticing a symptom and the first visit to the doctor materially alter the prQgnosis ? (2)If the delay is cut down will there be an appreciable increase in the number of Stage I cases treated ? (3)Can the delay be reduced by cancer education ?
Urokinase plasminogen activator receptor, beta 2-integrins, and Src-kinases within a single receptor complex of human monocytes.
Authors: J Bohuslav, V Horejsí, C Hansmann, J Stöckl, U H Weidle, O Majdic, I Bartke, W Knapp, H Stockinger
Journal: The Journal of Experimental Medicine (1995)

The glycosylphosphatidylinositol (GPI)-anchored membrane protein urokinase plasminogen activator-receptor (uPA-R; CD87) is one of the key molecules involved in migration of leukocytes and tumor cells. uPA bound to uPA-R provides the cell proteolytic potential used for degradation of extracellular matrix. uPA-R is also involved in induction of cell adhesion and chemotaxis. Here, we provide a molecular explanation for these uPA-R-related cellular events. By size fractionation of monocyte lysate and affinity isolation on its natural ligand uPA, we demonstrate uPA-R as a component of a receptor complex of relatively large size. Reprecipitation and immunoblotting techniques allowed us to detect the protein tyrosine kinases (PTKs) p60fyn, p53/56lyn, p58/64hck, and p59fgr as components of this "uPA-R complex". Activation of monocytes even with enzymatically inactivated uPA resulted in induction of tyrosine phosphorylation, suggesting modulation of uPA-R-associated PTKs upon ligand binding. In spite of their presence in large complexes, we did not find the GPI-linked proteins CD14, CD58, and CD59 in the uPA-R complex, which indicates the presence of different receptor domains containing GPI-linked proteins in monocytes. However, we identified the leukocyte integrins LFA-1 and CR3 as components of the uPA-R complex as indicated by coisolation of these molecules, as well as by cocapping and comodulation of uPA-R and leukocyte integrins on the monocyte surface. The assemblage of uPA-R, PTKs and membrane spanning beta 2-integrins in one receptor complex indicates functional cooperation. In regard to the involvement of these molecules in pericellular proteolysis, signal transduction, as well as adhesion and chemotactic movement, we suggest uPA-R complex as a potential cellular device for cell migration.
Bacterial and mammalian cell response to poly(3-sulfopropyl methacrylate) brushes loaded with silver halide salts
Authors: Madeleine Ramstedt, Barbro Ekstrand-Hammarström, Andrey V. Shchukarev, Anders Bucht, Lars Österlund, Martin Welch, Wilhelm T.S. Huck
Journal: Biomaterials (2008)
Correlation between ventilation and brain blood flow during sleep.
Authors: T V Santiago, E Guerra, J A Neubauer, N H Edelman
Journal: Journal of Clinical Investigation (1984)

The relationships between brain blood flow (BBF) and ventilation (VI) were studied during sleep in 13 goats. Unilateral BBF was continuously measured with an electromagnetic flow probe; total and regional BBF were assessed by the radioactive microsphere technique in four animals. Interacting changes in VI and BBF occurred during both slow wave (SWS) and rapid eye movement (REM) sleep. During SWS, significant decreases in VI and increases in arterial PCO2 occurred compared to wakefulness. BBF during SWS correlated linearly with arterial CO2 tension (PaCO2); nd the relationship was similar to that for awake goats breathing CO2. During REM sleep, VI was significantly less than both the awake (W) and SWS states due principally to a decrease in tidal volume. BBF during REM sleep was significantly and substantially increased compared with both the W and SWS states; this increase was shared by all brain areas. The increase in BBF during REM sleep was greater than that predicted from changes in PaCO2. In five goats provided with chronic sagittal sinus fistulae, arteriovenous oxygen difference was measured in separate studies and found to be significantly lower during REM sleep compared with W; brain O2 consumption was similar in magnitude in the REM and W states. Thus, the high BBF of REM sleep was also unexplained by an increase of brain metabolic activity. We conclude that, during SWS, increases in BBF are explained by hypoventilation and hypercapnia. In contrast, during REM sleep, BBF is substantially in excess of that expected from PaCO2 or brain metabolism. It is postulated that this excess of BBF during REM sleep could reduce the central chemoreceptor pH relative to that present in SWS. The combination of reduction of sensitivity to CO2 and lower tissue PCO2 during REM sleep makes it likely that the output of the central chemoreceptors during this state is less than that during SWS and wakefulness. This may contribute to the low tidal volume and respiratory irregularities of this sleep period.
Anthropometrically estimated total body water volumes are larger than modeled urea volume in chronic hemodialysis patients: Effects of age, race, and gender
Authors: John T. Daugirdas, Tom Greene, Thomas A. Depner, Cameron Chumlea, Michael J. Rocco, Glenn M. Chertow, None For The Hemodialysis (HEMO) Study Group
Journal: Kidney International (2003)
Norepinephrine spillover to plasma during steady-state supine bicycle exercise. Comparison of patients with congestive heart failure and normal subjects.
Authors: G J Hasking, M D Esler, G L Jennings, E Dewar, G Lambert
Journal: Circulation (1988)

This study was performed to determine the relative contributions of plasma norepinephrine clearance and norepinephrine release to the increase in plasma norepinephrine concentration that occurs during exercise and to determine whether the high rates of cardiac norepinephrine release from the heart and kidney in patients with heart failure are associated with diminished reserve for regional sympathetic nervous stimulation. During supine steady-state bicycle exercise at 50% of maximum voluntary exercise capacity, the plasma norepinephrine concentration of six patients with congestive heart failure rose from 385 +/- 88 to 2,200 +/- 497 pg/ml, whereas that of nine normal subjects rose from 208 +/- 21 to 882 +/- 257 pg/ml. The change in plasma concentration in both groups was due to an increase in norepinephrine spillover to plasma without a change in plasma norepinephrine clearance. In patients with heart failure, cardiac spillover increased from 80 +/- 26 to 528 +/- 265 ng/min during exercise, and renal spillover rose from 146 +/- 71 to 418 +/- 69 ng/min. In the normal subjects, cardiac spillover rose from 5 +/- 2 to 73 +/- 23 ng/min, and renal spillover increased from 76 +/- 27 to 275 +/- 106 ng/min. There is no evidence of a reduced reserve for overall or regional sympathetic stimulation in patients with heart failure. Reduced reflex responses in these patients are more likely due to end-organ refractoriness than to inadequate stimulation.
Complement Activation and Rituximab Distribution in CNS NHL—Letter
Authors: Silvia Hofer, Karin Mengele, Manfred Schmitt, Bernhard Pestalozzi, Stefan Aebi
Journal: Clinical Cancer Research (2015)

We have read with great interest the article by Kadoch and colleagues ([1][1]). Their pharmacokinetic model indicates rapid distribution of intraventricular rituximab from cerebrospinal fluid (CSF) into neural tissues and serum.

These findings may have more general implications for intrathecal (IT
Inflammatory and Oxidative Stress Responses of Healthy Young Adults to Changes in Air Quality during the Beijing Olympics
Authors: Wei Huang, Guangfa Wang, Shou-En Lu, Howard Kipen, Yuedan Wang, Min Hu, Weiwei Lin, David Rich, Pamela Ohman-Strickland, Scott R. Diehl, Ping Zhu, Jian Tong, Jicheng Gong, Tong Zhu, Junfeng Zhang
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Unprecedented pollution control actions during the Beijing Olympics provided a quasi-experimental opportunity to examine biologic responses to drastic changes in air pollution levels.Objectives: To determine whether changes in levels of biomarkers reflecting pulmonary inflammation and pulmonary and systemic oxidative stress were associated with changes in air pollution levels in healthy young adults.Methods: We measured fractional exhaled nitric oxide, a number of exhaled breath condensate markers (H+, nitrite, nitrate, and 8-isoprostane), and urinary 8-hydroxy-2-deoxyguanosine in 125 participants twice in each of the pre- (high pollution), during- (low pollution), and post-Olympic (high pollution) periods. We measured concentrations of air pollutants near where the participants lived and worked. We used mixed-effects models to estimate changes in biomarker levels across the three periods and to examine whether changes in biomarker levels were associated with changes in pollutant concentrations, adjusting for meteorologic parameters.Measurements and Main Results: From the pre- to the during-Olympic period, we observed significant and often large decreases (ranging from −4.5% to −72.5%) in levels of all the biomarkers. From the during-Olympic to the post-Olympic period, we observed significant and larger increases (48–360%) in levels of these same biomarkers. Moreover, increased pollutant concentrations were consistently associated with statistically significant increases in biomarker levels.Conclusions: These findings support the important role of oxidative stress and that of pulmonary inflammation in mediating air pollution health effects. The findings demonstrate the utility of novel and noninvasive biomarkers in the general population consisting largely of healthy individuals.
THE INFLUENCE OF ANION PENETRATING ABILITY ON URINARY ACIDIFICATION AND THE EXCRETION OF TITRATABLE ACID *
Authors: Norman Bank, William B. Schwartz
Journal: Journal of Clinical Investigation (1960)

IPrevious studies in the dog have demonstrated that during administration of neutral sodium phos- phate the rate of titratable acid excretion is directly proportional to the rate of phosphate excretion and is inversely related to plasma bicarbonate con- centration (1).Markedly acid urines containing near theoretical maximum amounts of titratable acid 1 were observed only in the presence of se- vere metabolic acidosis.More recently it has been shown that intense acidification of the urine can be achieved without the induction of acidosis (2).Normal subjects stimulated to retain sodium showed a rapid fall in urine pH to approximately 5.0 or below when infused with sodium sulfate, and it was concluded that increased reabsorption of sodium in the pres- ence of a poorly reabsorbable anion was responsible for this phenomlenon.Acidification of the urine has also been observed during administration of poorly reabsorbable anions to normal hu- man subjects during quiet standing (3) and to dogs in which glomerular filtration rate was re- duced by clamping of the renal artery (4)-experimental procedures known to induce a more complete reabsorption of filtered sodium.These observations raise the possibility that, even without acidosis, large numbers of hydrogen ions might be transported into the glomerular filtrate over a