tbuckley/cabot-search huggingface dataset:
An Antibody Against the Exosite of the Cloned Thrombin Receptor Inhibits Experimental Arterial Thrombosis in the African Green Monkey
Authors: Jacquelynn J. Cook, Gary R. Sitko, Bohumil Bednar, Cindra Condra, Michael J. Mellott, Dong-Mei Feng, Ruth F. Nutt, Jules A. Shafer, Robert J. Gould, Thomas M. Connolly
Journal: Circulation (1995)

Background Thrombin inhibitors have been shown to be efficacious in animal models of thrombosis and in initial human clinical trials. It is unknown if their efficacy is due to their prevention of thrombin-mediated fibrin formation or to an inhibitory effect on thrombin-stimulated platelet activation. Appropriate tools to address this question have not been available. Therefore, to evaluate the role of the platelet thrombin receptor in intravascular thrombus formation, a polyclonal antibody was raised against a peptide derived from the thrombin-binding exosite region of the cloned human thrombin receptor. This antibody serves as a selective inhibitor of the thrombin receptor for in vivo evaluation. Methods and Results The immune IgG (IgG 9600) inhibited thrombin-stimulated aggregation and secretion of human platelets. In contrast, it had no effect on platelet activation induced by other agonists including ADP, collagen, or the thrombin receptor–derived peptide SFLLR-NH 2 . IgG 9600 also inhibited thrombin-induced aggregation of African Green monkey (AGM) platelets. By Western blot analysis, the IgG identified a protein of ≈64 kD in homogenates of both human and AGM platelets. The effect of thrombin receptor blockade by this antibody on arterial thrombosis was evaluated in an in vivo model of platelet-dependent cyclic flow reductions (CFRs) in the carotid artery of the AGM. The intravenous administration of IgG 9600 (10 mg/kg) abolished CFRs in three monkeys and reduced CFR frequency by 50% in a fourth monkey. Ex vivo platelet aggregation in response to up to 100 nmol/L thrombin was completely inhibited during the 120-minute postbolus observation period in all four animals. There was a twofold increase in bleeding time, which was not statistically different from baseline, and ex vivo clotting time (APTT) was not changed. The glycoprotein IIb/IIIa receptor antagonist MK-0852 and the thrombin inhibitor recombinant hirudin also demonstrated inhibitory effects on CFRs at doses that did not significantly prolong template bleeding time. Control IgG had no effect on CFRs, ex vivo platelet aggregation, bleeding time, or APTT. Conclusions These results demonstrate that blockade of the platelet thrombin receptor can prevent arterial thrombosis in this animal model without significantly altering hemostatic parameters and suggest that the thrombin receptor is an attractive antithrombotic target.
B-cell tolerance. II. Trinitrophenyl human gamma globulin-induced tolerance in adult and neonatal murine B cells responsive to thymus- dependent and independent forms of the same hapten
Authors: JC Cambier, ES Vitetta, JW Uhr, Kettman JR
Journal: The Journal of Experimental Medicine (1977)

Neonatal splenic B cells which are responsive to thymus-dependent antigens (TD) are exquisitely susceptible to induction of tolerance (1,2). This state of tolerance is not mediated by suppressor T cells and is not a result of suboptimal macrophage function (1 and footnote one). In adult mice, induction of B-cell tolerance is not achieved with doses of antigen 1,000-fold higher (1) than those required to produce the same degree of unresponsiveness in neonates. In contrast to these results, studies with T-independent (TI) antigens indicate that neonatal and adult splenic B cells are equally susceptible to tolerance induction (3,4). However, such studies have not ascertained whether the neonate is more resistant to tolerance induction or the adult is hypersusceptible, i.e., does the induction of tolerance in cells responsive to TI antigens resemble that of adult or neonatal cells responsive to TD antigens? The answer is pertinent to determining the relative maturity of the B cells which can be tolerized or respond to TI or TD antigens. We report here the direct comparison of tolerogen sensitivity of adult and neonatal TD and TI responses by inducing tolerance in vitro with trinitophenyl human gamma globulin (TNP(17)HgG) and assaying unresponsiveness with TD and TI forms of the TNP determinant.
Acute promyelocytic leukemia with secondary myelofibrosis—Case report and review of the literature
Authors: Pankhi Dutta, Syed Hasan, Jina Bhattacharyya, Rajat Kumar, Manoranjan Mahapatra, Renu Saxena, Seema Tyagi, Sudha Sazawal, Hara Prasad Pati
Journal: American Journal of Hematology (2006)
Anatomy of an Illness as Perceived by the Patient
Authors: Phil Gunby
Journal: JAMA (1980)

Just before Christmas 1976, a report of the diagnosis and treatment of an illness appeared in a medical journal. There is, of course, nothing unusual about that, except that this report dealt with just one patient and was written by the patient himself— Norman Cousins, for more than 30 years an editor of<i>Saturday Review</i>magazine. As an intelligent, well-educated layman with a strong determination to overcome his illness, Cousins was disinclined to accept hospitalization and treatment unquestioningly. Some might consider him a "difficult" patient in that he refused to let technicians draw blood more frequently than once every three days and challenged the hospital diet as poorly balanced. But he also studied his own illness, speculated on its possible causes, and—in a kind of partnership with his physician—undertook some unusual approaches to overcoming it. Among these was the medicine of laughter, resulting from the reading of amusing books and
Surgery of the Tongue
Authors: W. G. Spencer
Journal: BMJ (1927)

The post-injury regenerative capacity of neurons is known to be mediated by a complex interaction of intrinsic regenerative pathways and external cues. In <i>Caenorhabditis elegans</i>, the initiation of axon regeneration is regulated by the non-muscle myosin light chain (MLC-4) phosphorylation signaling pathway. In this study, we have identified <i>svh-16</i>/<i>cdk-14</i>, a mammalian CDK14 homolog, as a positive regulator of axon regeneration in motor neurons. We then isolated the CDK-14-binding protein MIG-5/Disheveled (Dsh) and found that EGL-20/Wnt and the MIG-1/Frizzled receptor (Fz) are required for efficient axon regeneration. Further, we demonstrate that CDK-14 activates EPHX-1, the <i>C. elegans</i> homolog of the mammalian ephexin Rho-type GTPase guanine nucleotide-exchange factor (GEF), in a kinase-independent manner. EPHX-1 functions as a GEF for the CDC-42 GTPase, inhibiting myosin phosphatase, which maintains MLC-4 phosphorylation. These results suggest that CDK14 activates the RhoGEF–CDC42–MLC phosphorylation axis in a non-canonical Wnt signaling pathway that promotes axon regeneration. <b>Significance Statement:</b> Non-canonical Wnt signaling is mediated by Fz, Dsh, Rho-type GTPase, and non-muscle MLC phosphorylation. This study identified <i>svh-16</i>/<i>cdk-14</i>, which encodes a mammalian CDK14 homolog, as a regulator of axon regeneration in <i>Caenorhabditis elegans</i> motor neurons. We show that CDK-14 binds to MIG-5/Dsh and that EGL-20/Wnt, MIG-1/Fz, and EPHX-1/RhoGEF are required for axon regeneration. The phosphorylation-mimetic MLC-4 suppressed axon regeneration defects in <i>mig-1</i>, <i>cdk-14</i>, and <i>ephx-1</i> mutants. CDK-14 mediates kinase-independent activation of EPHX-1, which functions as a GEF for CDC-42 GTPase. Activated CDC-42 inactivates myosin phosphatase and thereby maintains MLC phosphorylation. Thus, the non-canonical Wnt signaling pathway controls axon regeneration via the CDK-14–EPHX-1–CDC-42–MLC phosphorylation axis.
1164-126 Characteristics of Duchenne and Becker muscular dystrophy patients in the pediatric cardiomyopathy registry
Authors: David Connuck, Lynn Sleeper, Jeffrey Towbin, Steven Colan, Gerald Cox, Leigha Cuniberti, John Orav, Bonnie Anne Salbert, Steven Lipshultz
Journal: Journal of the American College of Cardiology (2004)
Evidence of a Relationship Between Childhood-Onset Type I Diabetes and Low Groundwater Concentration of Zinc
Authors: Bengt Haglund, Katarina Ryckenberg, Olle Selinus, Gisela Dahlquist
Journal: Diabetes Care (1996)

OBJECTIVE Zinc deficiency has shown to increase the risk for diabetes in diabetes-prone experimental animals. Low concentrations of zinc have also been shown in serum of recent onset cases with IDDM. The present study examines the hypothesis that exposure to a low concentration of zinc in drinking water could increase the risk for future onset of IDDM. RESEARCH DESIGN AND METHODS Using the Swedish childhood diabetes registry and data on residence 3 years before the onset of disease, a case-control study was designed comparing cases and control subjects with estimates of groundwater contents of zinc obtained in biogeochemical samples from areas of residence. RESULTS A high groundwater concentration of zinc was associated with a significant decrease in risk (odds ration [OR] = 0.8; 95% CI = 0.7–0.9). The same OR was obtained when the model included information of other metals that might act as possible confounders (chromium, vanadium, cobalt selenium, cadmium, lead, and mercury). In small rural areas, in which drinking water is taken from local wells and thus is closely associated with the groundwater content within the area, an even stronger association between zinc and diabetes (OR = 0.6; 95% CI = 0.4–0.9) was found. CONCLUSIONS It is concluded that this study for the first time provides evidence that a low groundwater content of zinc, which may reflect long-term exposure through drinking water, is associated with later development of childhood onset diabetes.
Opening up data at the European Medicines Agency
Authors: P. C. Gotzsche, A. W. Jorgensen
Journal: BMJ (2011)

Widespread selective reporting of research results means we don't know the true benefits and harms of prescribed drugs. <b>Peter Gøtzsche</b> and <b>Anders Jørgensen</b> describe their efforts to get access to unpublished trial reports from the European Medicines Agency
THE DANGER AND PREVENTION OF SEVERE CARDIAC STRAIN DURING ANESTHESIA
Authors: W. D. GATCH
Journal: JAMA (1913)

We started the investigation which is here reported to determine the effects of the Trendelenburg position on the circulation and respiration, and to formulate rules for its safe employment. We had become convinced from cases observed by ourselves, and from communications from a large number of surgeons and anesthetists, that this posture may at times endanger the life of the patient during anesthesia. Our experiments, checked by clinical observations, have demonstrated, to our own satisfaction at least, that this conclusion is correct. But they have also shown that the Trendelenburg position is only one of several agencies which act in the same manner, namely, by increasing to a dangerous extent the flow of the blood to the heart. A study of cases of death during anesthesia under present-day conditions of surgery will show, we think, that more fatalities result from this cause than from its opposite—diminished supply brought
Smallpox in a Child Aged 3 Days
Authors: Y. S. N. Rao, N. R. Ratnakannan, K. S. Balasubramaniam, K. N. Gopalan
Journal: BMJ (1954)

ACIDAEMIC COMA BaDISH 1459 urea was continuing to rise.Lange et al. (1951) have shown that severe acidaemia (pH 6.8-7.2) causes a large increase in cardiac output with fall in peripheral resistance: this may account for the fact that, on admission, blood from the antecubital vein was arterial in colour despite consider- able dehydration.Summary A case of acidaemic coma with hypokalaemia, pre- cipitated by acute pyelonephritis, four years after bilateral uretero-sigmoid anastomosis, is described.Recovery occurred following the infusion of alkali, rehydration, intravenous and oral potassium, and a course of chlortetracycline.Hyperventilation with low levels of plasma bicarbon- ate and CO2 tension persisted for two weeks after restoration of the blood pH to normal.Attention is drawn to the value of serial measurements of arterial pH as a rapid and accurate method of controlling alkali therapy.I wish to thank Dr. Thomas Simpson and Mr. H. 0. Blauvelt for permission to publish this case; and Mr. Ronald Smith for the estimations of sodium, potassium, chloride, and urea.APPENDIX Arterial blood samples were taken, under local analgesia, from the brachial artery into all-glass syringes lubricated with a few drops of heparin (5,000 units per ml.) only, using a No. 1 Luer needle.Beads of mercury were subse- quently introduced to obtain even mixing of blood and heparin.The patient's temperature was taken while the artery was compressed firmly for three minutes.The blood was allowed to cool to room temperature and its pH measured within thirty minutes of sampling with a Cam- bridge pH meter and Stadie closed glass electrode.The meter was standardized with phosphate-citrate buffers of pH 7 and 7.4 (B.D.H. electrometrically tested).Correction of the observed pH to the patient's body temperature was made by Rosenthal's (1948) factor.Arterial pC02 can be calculated from pH and total plasma C02 content using the Henderson-Hasselbalch equation.
847 EFFECT OF COFFEE AND GREEN TEA CONSUMPTION ON LIVER ENZYME AND METABOLIC SYNDROME IN KOREAN POPULATION
Authors: D.W. Jun, E.K. Kim, H.S. Choi, Y.I. Kown, W. Sohn, O.W. Kwon, K.N. Lee, H.L. Lee, O.Y. Lee, B.C. Yoon, T.Y. Kim, J.H. Sohn
Journal: Journal of Hepatology (2011)
Multiple discrete encephalitogenic epitopes of the autoantigen myelin basic protein include a determinant for I-E class II-restricted T cells.
Authors: S S Zamvil, D J Mitchell, M B Powell, K Sakai, J B Rothbard, L Steinman
Journal: The Journal of Experimental Medicine (1988)

Immunization with the autoantigen myelin basic protein (MBP) causes experimental allergic encephalomyelitis (EAE). Initial investigations indicated that encephalitogenic murine determinants of MBP were located only within MBP 1-37 and MBP 89-169. Encephalitogenic T cell epitopes within these fragments have been identified. Each epitope is recognized by T cells in association with separate allelic I-A molecules. A hybrid I-E-restricted T cell clone that recognizes intact mouse (self) MBP has been examined. The epitope recognized by this clone includes MBP residues 35-47. When tested in vivo, p35-47 causes EAE. T cell recognition of p35-47 occurs only in association with I-E molecules. These results provide the first clear example that antigen-specific T cells restricted by I-E class II molecules participate in murine autoimmune disease. Furthermore, it is clear that there are multiple (at least three) discrete encephalitogenic T cell epitopes of this autoantigen, each recognized in association with separate allelic class II molecules. These results may be relevant to human autoimmune diseases whose susceptibility is associated with more than one HLA-D molecule.
Radiofrequency ablation treatment for small breast cancer.
Authors: M Noguchi, M Earashi, A Motoyoshi
Journal: Cancer Research (2009)

Abstract Abstract #5155 Aims: There is increasing demand for minimally invasive and non-surgical treatment in breast cancer. Although radiofrequency (RF) ablation seems the most promising non-surgical treatment for small breast cancer, its relevance has been controversial. This study was performed to determine the feasibility and the safety of treating small breast cancer with RF ablation. Methods: In this study, all patients had a localized breast cancer of 2.0 cm or less in greatest diameter. The tumors were confirmed to be localized lesions by ultrasonography, mammography, and enhanced MRI or CT. Before treatment, core needle or mammotome biopsy was performed to obtain the tumor tissue for establishing the histological diagnosis and the status of hormonal receptors and HER-2 expression. A model 15000 generator with a seven-array Starbusrt XL needle-electrode Model 70 (RITA Medical System) was used for RF ablation. In the first series, 17 patients underwent RF ablation and sentinel lymph node (SLN) biopsy followed immediately by wide resection (n=13) or total mastectomy (n=4). Axillary dissection was performed in 5 patients with positive SLN. On the other hand, 15 patients underwent RF ablation and SLN biopsy in the second series. Axillary dissection was performed in 3 patients with positive SLN. The ablated lesion was excised by mammotome after several months later. The ablated tumor tissue was examined histologically with H&amp;E staining and NADH-diaphorase staining to assess tumor cell viability. Patients who underwent wide resection or RF ablation alone received breast irradiation, and all of the patients were treated with systemic therapy according to the St. Gallen recommendation. Results: Histological examination with H&amp;E staining revealed a spectrum of changes ranging from complete coagulation necrosis to normal-appearing tumor cells, but NADH-diaphorase staining revealed no viable tumor cells in the either series. No patient developed to local or breast recurrence in the first series with a median follow-up period of 46 months (range: 34-61 months), and in the second series with a median follow-up period of 23 months (range: 12-32 months). However, one patient in the first series and another in the second series developed to the distant metastases, although they are alive with systemic treatment. The cosmesis of conserved breast was excellent in the second series more than in the first series, and no adverse effect such as skin burn or persistent hard lump was observed in the second series. Conclusions: RF ablation is feasible for small breast cancer. To achieve wide acceptance, however, further studies are needed to determine whether the use of RF ablation for small breast cancer can provide local control and survival rates equivalent to those of conventional breast-conserving treatment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5155.
Mitral A velocity wave transit time to the outflow tract as a measure of left ventricular diastolic stiffness. Hemodynamic correlations in patients with coronary artery disease.
Authors: R G Pai, M Suzuki, J T Heywood, D R Ferry, P M Shah
Journal: Circulation (1994)

Subjects in sinus rhythm have two distinct diastolic flow velocities in the left ventricular (LV) outflow tract directed toward the aortic valve. These follow E and A waves of the transmitral flow and are referred to as Er and Ar waves, respectively. The A wave transit time from the mitral valve to the LV outflow tract is shorter than that of the E wave and is shorter in those with LV hypertrophy and the aged, suggesting its possible dependence on LV late diastolic stiffness. METHODS AND RESULTS. We measured the peak-to-peak and onset-to-onset A wave transit times from the mitral valve to the LV outflow tract (AArp and AAro intervals, respectively) using Doppler echocardiography in 20 patients undergoing left heart catheterization for evaluation of coronary artery disease. These intervals were correlated with indices of LV late diastolic stiffness obtained from high-fidelity LV pressure tracings and angiographic volume assessments. The AArp and AAro intervals correlated significantly with LV Dp/DV (conventionally dP/dV) (r = -.68 and -.83, respectively), volume stiffness, V.Dp/DV (r = -.74 and -.80, respectively) and LV (V/P) (Dp/DV) (r = -.69 and -.74, respectively). The AAro interval correlated better with the square roots of LV Dp/DV and volume stiffness (r = -.86 and -.87, respectively).We conclude that AArp and AAro intervals are easily obtainable Doppler parameters that reflect LV late diastolic stiffness in patients with coronary artery disease and possibly in other patients groups.
DANGEROUSNESS-ARREST RATE COMPARISONS OF DISCHARGED PATIENTS AND THE GENERAL POPULATION
Authors: JONAS R. RAPPEPORT, GEORGE LASSEN
Journal: American Journal of Psychiatry (1965)

The incidence of arrest for 2 Maryland psychiatric populations, 1947 and 1957, were obtained for the 5 years preceding and following their discharge from psychiatric hospitals. Comparison of their arrest rates with that of the general population indicates that for some serious offenses the psychiatric population has a higher arrest rate than the general population. Comparison of pre- and post-hospitalization arrest rates were made and revealed no differences, nor did a comparison of the arrest rates of the two populations reveal any changes that might reflect the use of the newer treatment techniques. An appendix of 4 tables has been added. Tables 1 and 2 show the relationship of our arrest rates to those of the general population. Tables 3 and 4 show the incidence of recidivism of our populations.
Amphetamine and Glaucoma
Authors: L. H. G. Moore
Journal: BMJ (1960)

<h3>Background</h3> The gut microbiome is associated with the immune function of the host. No consensus has been reached regarding to the association between microbiota and the treatment response to immune checkpoint inhibitor (ICI). This study is designed to explore the relationship between gut microbiome composition and clinical outcomes in patients with advanced cancer treated with ICI. <h3>Methods</h3> Fifty patients were enrolled in this study. Fecal samples were collected at the baseline, 3 months after treatment and when disease progression was noted. To explore the gut microbiota as a potential predictive biomarker for immunotherapy, 16S ribosome RNA gene sequencing was used to analyze the gut microbiota profiles. Peripheral immunity parameters were determined by multicolor flow cytometry and cytokine array. Alpha-diversity of healthy individuals was used as a cut-off. <h3>Results</h3> When subgrouping patients into benefiter and non-benefiter according to the clinical response assessed, non-benefiter patients harbored lower alpha-diversity of gut microbiome at the baseline. Patients with low microbiome diversity had poor progression-free survival (HR=0.569, p=0.219) when compared to those with high diversity. Compositional difference was observed between the two groups as well with the enrichment of g_Fusicatenibacter in benefiters whereas f_Veillonellaceae enriched in non-benefiters. Analysis of immune responses using multicolor flow cytometry revealed that patients with a high diversity of gut microbiota had decreased CD4+/CD25+/FoxP3+ regulatory T cells in response to ICI. After ICI treatment the CD4/CD8 ratio of PBMCs was decreased in clinical benefiter. The serum MIF and CXCL12 levels were decreased in clinical benefiter. <h3>Conclusions</h3> Low alpha diversity of the gut microbiota is associated with poor response to immune checkpoint inhibitors in patients with advanced cancer. Further confirmation in the clinical trials is warranted. <h3>Acknowledgements</h3> The authors thank all the members of the Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, for their invaluable help. The study and data collection processes were funded by the grants to John WC Chang from Chang Gung Memorial Hospital (Grant No. CIRPG3H0061~2). <h3>Ethics Approval</h3> The study was approved by the Institutional Review Board of Chang Gung Memorial Hospital, approval number 201801261B0. <h3>Consent</h3> Written informed consent was obtained from the patients for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.