tbuckley/cabot-search huggingface dataset:
Hunterian Lecture ON CANCER OF THE CERVIX: Delivered before the Royal College of Surgeons, January 25th, 1924
Authors: S. Forsdike
Journal: BMJ (1924)

t MDc BJit old and truest sense) that links together all our diverse interests.We must never lose sight of tlle essential unity/ of pathological processes.Tlhough clinical medicine sees one aspect of a disease, anid radiology aniother, and morbid anatom-ny a third, aind parasitology a fourtlh, the disease is one and the samle, and our best conception of it is obtained, pot by undue insistence uponi any on-e of these aspects, but 'by a proportioniate mingling of the pictures presented by all.He who achieves the most complete conceptioii of a disease in his minld is the most likely to enivisage the appropriate treatmenlt and get the best result.None of lls cani 4ffoid to neglect the facts elicited by the metlhods of otlher.s;Iindeed, our own methods will yield us more facts, and a clearer vision, in exact proporttionll as we allow them to be guided and controlled by the methods of others.It is of lhe utmost importance that we keep our minds alert and rlee from stereotywed ideas, yet bound ali-ays, fettereed even, by the principles of science and rieason, with a healtlhy scepticism withal-that saving grace so essential to the scientific mind.Let us remember that our l)preset notions of diseases, even whell we think them very complete, are probably extremely crude.We have already ample expe- rience that this is so.Not only are they crulde in respect of the extent and the complexity of the disease process, as instanced earlier in this addr ess, but in respect of the sourse diseases run and their response to our efforts at treatment.The problems of pathology become more elusive and yet more fascinating the closetrwe study them.It is a glorious contribution to such study that you are making to-day by means of radiology, both ill its diagnostic and in its therapeutic values.The memory of him in whose nameWe meet together to-day is, I feel sure, being well served by you who follow him.I wish to congratulate youi upon the fine work with which you are supplpementing his and other pioneer achievements, and I shall have justified myself if anything I have said serves to stimulate you to furtherefforts and yet greater results.
S59 Chemo-immunotherapy of mesothelioma: depletion of established, suppressive CD4 T cells is critical to achieving cures in a murine model
Authors: H. J. Steer, A. Cleaver, A. Nowak, B. Robinson, R. Lake
Journal: Thorax (2011)

<h3>Introduction</h3> Mesothelioma is incurable and new treatment strategies are urgently needed. It has long been recognised that malignant cells can be attacked by the immune system but immunotherapy is only starting to emerge as an additional modality of treatment for cancer. The crucial role that helper CD4 T cells play in orchestrating CD8 T cell and other anti-tumour responses has only recently been appreciated. However the CD4 population contains effector and suppressive subsets with diverse and opposing functions. Although the effects of pemetrexed on tumour immunity are still being defined, gemcitabine is known to synergise with immunotherapy by causing tumour cell death, releasing tumour antigen and depleting suppressive immune cells. We investigated the role that different types of CD4 cell play in CD8 anti-tumour immune responses and how the CD4 response could be best manipulated to optimise outcomes to chemo-immunotherapy. <h3>Methods</h3> Thy1.2+ve balb/c mice bearing mesothelioma tumours expressing the neoantigen haemagglutinin (HA), were treated with gemcitabine and adoptive transfer of tumour antigen (HA) specific thy1.1+ve CD8 T cells and thy1.1+ve CD4 cells which had been differentiated in vitro into Th1s, Th2s, Th17s or regulatory T cells (Tregs). The activity of the adoptively transferred cells in vivo was tracked by identifying recovered thy1.1+ve cells by flow cytometry. <h3>Results</h3> In the prophylactic treatment setting, in vitro differentiated tumour antigen specific Th1s led to rejection of tumours inoculated 1 day later in around 40% of mice. However there was minimal activity against established, gemcitabine-treated tumours. Recovery of adoptively transferred CD8 T cells revealed that in established tumours, CD4s were unable to help cognate CD8 cells expand and infiltrate tumours. However if endogenous CD4s were depleted prior to treatment then CD8 tumour infiltration was significantly increased and cures were seen in around two-thirds of mice. <h3>Conclusions</h3> These results suggest that once a tumour is established, an over-riding endogenous suppressive CD4 response prevents effector CD4s from helping CD8 T cells to eradicate tumours. Removal of suppressive CD4 cells was critical to achieving cures with chemo-immunotherapy.
Failure of Doxycycline as a Causal Prophylactic Agent against Plasmodium falciparum Malaria in Healthy Nonimmune Volunteers
Authors: Moshe J. Shmuklarsky
Journal: Annals of Internal Medicine (1994)

Objective: To determine whether doxycycline, 100 mg administered as a single daily oral dose, is effective as a causal prophylactic agent, an agent active against the pre-erythrocytic liver stage of Plasmodium falciparum malaria parasites, in healthy nonimmune persons. If effective, the recommendation by the Centers for Disease Control and Prevention (CDC) that doxycycline be continued for 4 weeks after returning from malaria-endemic areas could be shortened to 1 week. Design: Randomized, double-blind, placebo-controlled trial. Setting: Medical ward at the U.S. Army Research Institute of Infectious Diseases, Fort Detrick, Maryland. Participants: 18 nonimmune, healthy, adult male volunteers, age 21.7 ±2.9 (SD) years, were enrolled in two groups, one of 8 persons and one of 10 persons. Six participants in the first group and 7 in the second group received doxycycline. The remaining participants received placebo. Two volunteers were dropped from the study, leaving 16 participants for analysis. Intervention: Each participant received doxycycline, 100 mg, or placebo in a single daily oral dose starting 3 days before exposure to P. falciparum–infected mosquitoes and ending 6 days after exposure. Measurements: Monitoring for parasitemia, plasma doxycycline concentrations, and mosquitoes' salivary-gland sporozoite grade. Results: 6 of 6 (100% [95% CI, 54% to 100%]) participants on doxycycline in the first group and 2 of 6 (33% [CI, 4% to 78%]) in the second group were protected from malaria. No differences were found between protected and nonprotected participants in the doxycycline elimination half-life (T1/2) (20.8 ±5.0 h compared with 21.9 ±5.2 h), the steady-state average plasma concentration (1626 ±469 ng/mL compared with 1698 ±651 ng/mL), or other pharmacokinetic parameter estimates. The mean mosquito salivary-gland sporozoite grade was significantly higher (P = 0.02) in protected (3.5 ±0.3) than in nonprotected persons (3.1 ±0.1). Overall, 8 of 12 persons on doxycycline were protected from malaria, yielding a causal prophylactic efficacy rate of 67% (CI, 35% to 90%). Conclusions: A dosing regimen of doxycycline, 100 mg once daily, administered as a causal prophylactic agent against P. falciparum malaria in healthy, nonimmune volunteers, had an unacceptably high failure rate. Therefore, the CDC recommendation that doxycycline should be taken daily starting 1 to 2 days before travel, during travel, and for 4 weeks after travel should still be followed.
The International Executive Committee of the Pan American Medical Congress.—
Authors: Charles A L Reed
Journal: JAMA (1892)

The committee on organization of the Pan American Medical Congress at its meeting at St. Louis last October, elected the following International Executive Committee: The Argentine Republic, Dr. Pedro Lagleyze, Beunos Ayres; Bolivia, Dr. Emelio Di Tomassi, LaPaz; Brazil, Dr. Carlos Costa, Rio de Janeiro; British North America, Dr. James F. W. Ross, Toronto; British West Indies, Dr. James A. De Wolf, Port of Spain; Chili, Dr. Moises Amaral, Santiago; United States of Colombia, Dr. P. M. Ibañez, Bogota; Costa Rica, Dr. Daniel Nuñez, San Jose; Ecuador, Dr. Ricardo Cucalon, Guayquil; Guatamala, Dr. José Monteris, Guatamala Nueon; Hayti, Dr. D. Lamothe, Port au Prince; Spanish Honduras, Dr. George Bernhardt, Fegucigalpo; Mexico, Dr. Fornás Noriega, City of Mexico; Nicaragua, Dr. J. I. Urtecho, Grenada; Peru, Dr. J. Cassamira Ulloa, Lima; Salvador, Dr. David J. Guzman, San Salvador; Spanish West Indies, Dr. Juan Santos Fernandez, Havana; United States, Dr. A. Vander Veer,
Characterization of Sodium Channel α- and β-Subunits in Rat and Mouse Cardiac Myocytes
Authors: Jyoti Dhar Malhotra, Chunling Chen, Ilaria Rivolta, Hugues Abriel, Ricky Malhotra, Laura N. Mattei, Frank C. Brosius, Robert S. Kass, Lori L. Isom
Journal: Circulation (2001)

Sodium channels isolated from mammalian brain are composed of alpha-, beta(1)-, and beta(2)-subunits. The composition of sodium channels in cardiac muscle, however, has not been defined, and disagreement exists over which beta-subunits are expressed in the myocytes. Some investigators have demonstrated beta(1) expression in heart. Others have not detected any auxiliary subunits. On the basis of Northern blot analysis of total RNA, beta(2) expression has been thought to be exclusive to neurons and absent from cardiac muscle.The goal of this study was to define the subunit composition of cardiac sodium channels in myocytes. We show that cardiac sodium channels are composed of alpha-, beta(1)-, and beta(2)-subunits. Nav1.5 and Nav1.1 are expressed in myocytes and are associated with beta(1)- and beta(2)-subunits. Immunocytochemical localization of Nav1.1, beta(1), and beta(2) in adult heart sections showed that these subunits are expressed at the Z lines, as shown previously for Nav1.5. Coexpression of Nav1.5 with beta(2) in transfected cells resulted in no detectable changes in sodium current.Cardiac sodium channels are composed of alpha- (Nav1.1 or Nav1.5), beta(1)-, and beta(2)-subunits. Although beta(1)-subunits modulate cardiac sodium channel current, beta(2)-subunit function in heart may be limited to cell adhesion.
Eclampsia in a patient who had had a renal transplant.
Authors: P F Williams, I Jelen
Journal: BMJ (1979)

no distal swelling or pain in the metacarpophalangeal or interphalangeal joints and where it is usually easy to flex the finger fully but difficult to straighten it again.The natural history of diabetic cheiroarthropathy is not clear but the joint contractures may not improve.3There have been no reports of the benefit of tenolysis, and our case shows that allowing full movements of the finger joint may prevent secondary joint contracture and that the pain and swelling settle over six to nine months.
Infertile couples favour Spain and Czech Republic for treatment because of good supply of donor gametes, study shows
Authors: C. Dyer
Journal: BMJ (2011)

<h3>Objectives</h3> To assess the safety and effectiveness of administering local steroid injections in an operational field hospital environment. <h3>Method</h3> A prospective study of patients presenting to the physiotherapy department at the British Military Hospital (BMH) Shaibah, Iraq was undertaken from July 2006 – September 2006. Patients with a condition amenable to local steroid injection and who had not improved with conservative therapy were considered for the study. They then underwent local injection with steroid and local anaesthetic. <h3>Results</h3> During this period 12 patients were identified that fitted the criteria for local steroid injection. This represented 7% (12/179) of patients who were seen by the physiotherapy department in either an in or out-patient setting. All patients were injected with local anaesthetic and steroid injection with a single dose of intravenous antibiotic as antimicrobial cover. 10/12 (83.3%) were able to return to their unitwithin this theatre of operation. The only complication was one case of post injection flare of pain, which settled after 48 hours. <h3>Conclusion</h3> The use of local steroid injection, as an adjunct to physical therapy, can enable service personnel to remain in the theatre of operations. These patientsmay have otherwise required aero medical evacuation. We consider the use of a local steroid injection to be a safe and effective intervention in certain patients where conservative measures alone do not work. This study highlights the safety of using steroid injections in an operational field hospital setting. Further large scale studies may help corroborate this conclusion.
Activated recombinant human coagulation factor VII (rFVIIa) therapy for abdominal bleeding in patients with inhibitory antibodies to factor VIII
Authors: Howard A. Liebman, Juan Chediak, Kenneth I. Fink, Angel G. Galvez, Prabodh C. Shah, Ronald L. Sham
Journal: American Journal of Hematology (2000)

Eight patients with inhibitors to factor VIII (4 hemophilia A and 4 nonhemophilic) were treated with recombinant activated factor VII (rFVIIa) to control severe abdominal bleeding. The recombinant factor was supplied under an open-label, emergency-use program to patients previously unresponsive to one or more alternative therapies. Therapy with rFVIIa was administered for nine separate bleeding events; one patient was treated for two separate bleeding episodes. Patients were treated for an average of 9 days and received a mean total dose of 5.2 mg of rFVIIa for control of bleeding. Treatment was considered successful and hemostasis adequate in 7 of the 9 episodes (78%). Treatment with rFVIIa was partially successful in one other episode. Four patients in this series experienced serious adverse events; all the adverse events were considered unrelated to rFVIIa therapy. The results of this limited series indicate that rFVIIa is an effective means of managing life-threatening abdominal bleeding in individuals with hemophilia or acquired antibodies to factor VIII. Am. J. Hematol. 63:109–113, 2000. © 2000 Wiley-Liss, Inc.
Mortality in Celiac Disease, Intestinal Inflammation, and Gluten Sensitivity
Authors: Peter H. R. Green
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Characterization of an acquired inhibitor to coagulation factor V. Antibody binding to the second C-type domain of factor V inhibits the binding of factor V to phosphatidylserine and neutralizes procoagulant activity.
Authors: T L Ortel, M A Quinn-Allen, L A Charles, D Devore-Carter, W H Kane
Journal: Journal of Clinical Investigation (1992)

Coagulation Factor V is an essential component of the prothrombinase complex, which activates the zymogen prothrombin to thrombin. A patient was described who developed a Factor V inhibitor that neutralized the procoagulant activity of Factor V and resulted in a fatal hemorrhagic diathesis (Coots, M. C., A. F. Muhleman, and H. I. Glueck. 1978. Am. J. Hematol. 4:193-206). This inhibitor was shown to be an IgG antibody that bound to the light chain of Factor V. Using a series of light chain deletion mutants, we have found that this antibody binds to the second C-type domain of the light chain. Both inhibitor IgG and Fab fragments rapidly neutralized the procoagulant activity of Factor Va, implying that the neutralization resulted from specific binding to the C2 domain. We have previously demonstrated that deletion of the C2 domain results in loss of procoagulant activity, as well as loss of phosphatidylserine-specific binding. Confirming these results, both inhibitor IgG and Fab fragments interfered with phosphatidylserine-specific binding of Factor V. Conversely, preincubation of Factor Va with procoagulant phospholipids protected the cofactor from inactivation by the inhibitor. Our results suggest that this inhibitor neutralizes the procoagulant activity of Factor Va by interfering with the C2-mediated interaction with phospholipid surfaces, thereby disrupting formation of the prothrombinase complex.
The genome of the hydatid tapeworm Echinococcus granulosus
Authors: Huajun Zheng, Wenbao Zhang, Liang Zhang, Zhuangzhi Zhang, Jun Li, Gang Lu, Yongqiang Zhu, Yuezhu Wang, Yin Huang, Jing Liu, Hui Kang, Jie Chen, Lijun Wang, Aojun Chen, Shuting Yu, Zhengchao Gao, Lei Jin, Wenyi Gu, Zhiqin Wang, Li Zhao, Baoxin Shi, Hao Wen, Renyong Lin, Malcolm K Jones, Brona Brejova, Tomas Vinar, Guoping Zhao, Donald P McManus, Zhu Chen, Yan Zhou, Shengyue Wang
Journal: Nature Genetics (2013)

Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCavβ1 may be associated with praziquantel sensitivity. Our study offers insights into host interaction, nutrient acquisition, strobilization, reproduction, immune evasion and maturation in the parasite and provides a platform to facilitate the development of new, effective treatments and interventions for echinococcosis control.
Vanadate normalizes hyperglycemia in two mouse models of non-insulin-dependent diabetes mellitus.
Authors: J Meyerovitch, P Rothenberg, Y Shechter, S Bonner-Weir, C R Kahn
Journal: Journal of Clinical Investigation (1991)

We have studied the effects of oral administration of vanadate, an insulinometic agent and a potent inhibitor of phosphotyrosyl protein phosphatase (PTPase) in vitro, on blood glucose and PTPase action, in two hyperinsulinemic rodent models of non-insulin-dependent diabetes mellitus (NIDDM). Oral administration of vanadate (0.25 mg/ml in the drinking water) to ob/ob mice for 3 wk lowered blood glucose level from 236 +/- 4 to 143 +/- 2 mg/dl without effect on body weight. Administration of vanadate to db/db mice produced a similar effect. Electron microscopic examination revealed no signs of hepatotoxicity after 47 d of treatment. There was a slight reduction in insulin receptor autophosphorylation when tested by immunoblotting with antiphosphotyrosine antibody after in vivo stimulation, and the phosphorylation of the endogenous substrate of the insulin receptor, pp185, was markedly decreased in the ob/ob mice. Both cytosolic and particulate PTPase activities in liver of ob/ob mice measured by dephosphorylation of a 32P-labeled peptide corresponding to the major site of insulin receptor autophosphorylation were decreased by approximately 50% (P less than 0.01). In db/db diabetic mice, PTPase activity in the cytosolic fraction was decreased to 53% of control values (P less than 0.02) with no significant difference in the particulate PTPase activity. Treatment with vanadate did not alter hepatic PTPase activity as assayed in vitro, or receptor and substrate phosphorylation as assayed in vivo, in ob/ob mice despite its substantial effect on blood glucose. These data indicate that vanadate is an effective oral hypoglycemic treatment in NIDDM states and suggest that its major effects occurs distal to the insulin receptor tyrosine kinase.
Genome Editing of Isogenic Human Induced Pluripotent Stem Cells Recapitulates Long QT Phenotype for Drug Testing
Authors: Yongming Wang, Ping Liang, Feng Lan, Haodi Wu, Leszek Lisowski, Mingxia Gu, Shijun Hu, Mark A. Kay, Fyodor D. Urnov, Rami Shinnawi, Joseph D. Gold, Lior Gepstein, Joseph C. Wu
Journal: Journal of the American College of Cardiology (2014)
Aging — Lost in Translation?
Authors: Pankaj Kapahi, Jan Vijg
Journal: New England Journal of Medicine (2009)

Caloric restriction and the inhibition of molecular pathways extend life in certain animal models. Female mice deficient in a molecule downstream of the TOR (target of rapamycin, now known as sirolimus) pathway not only have longer lives than control mice but also are protected against age-related decline that affects bone, muscle, and immunity.
Re: Bas W.G. van Rhijn, Theo H. van der Kwast, Sultan S. Alkhateeb, et al. A New and Highly Prognostic System to Discern T1 Bladder Cancer Substage. Eur Urol 2012;61:378–84
Authors: Anna Orsola, Inés de Torres, Juan Morote
Journal: European Urology (2012)
Donor cell myelodysplastic syndrome after allogeneic stem cell transplantation responding to donor lymphocyte infusion: Case report and literature review
Authors: Rami Komrokji, Jainulabdeen J. Ifthikharuddin, Raymond E. Felgar, Camille N. Abboud, Lucy A. Wedow, Anna Connaughton, John M. Bennett
Journal: American Journal of Hematology (2004)

Abstract Allogeneic hematopoietic stem cell transplantation (SCT) is a potentially curative treatment for patients with myelodysplastic syndrome (MDS). Relapses after transplantation however, are not uncommon and are usually due to re‐emergence of a recipient derived, neoplastic, stem cell clone. We report a unique case of MDS recurring 5 months after non‐myeloablative, sibling, allogeneic SCT. Interestingly, chimerism analysis at relapse showed hematopoiesis to be entirely of donor origin confirming donor cell MDS. Donor lymphocyte infusion (DLI) produced a hematological response lasting several months. Our review of the literature shows donor‐derived MDS to be very rare, with only four such cases described previously. In this report, we describe the details of our case and discuss putative mechanisms underlying the genesis of donor cell MDS and the observed response to DLI. Am. J. Hematol. 76:389–394, 2004. © 2004 Wiley‐Liss, Inc.