tbuckley/cabot-search huggingface dataset:
A phase I study of MORAb-003, a fully humanized monoclonal antibody against folate receptor alpha, in advanced epithelial ovarian cancer
Authors: K. M. Bell-McGuinn, J. Konner, N. Pandit-Taskar, S. Gerst, N. Nicolaides, P. Sass, L. Grasso, S. Weil, M. Phillips, C. Aghajanian
Journal: Journal of Clinical Oncology (2007)

5553 Background: Folate receptor alpha (FRA) is over-expressed in the majority of epithelial ovarian cancers (EOC) but is largely absent from normal tissue. MORAb-003 is a humanized monoclonal antibody (MAb) to FRA. Binding of MORAb-003 to FRA can prevent phosphorylation of substrates specific for Lyn kinase, suppress proliferation of cells over-expressing FRA, mediate FRA-positive tumor cell killing via antibody-dependent cellular and complement-dependent mechanisms, and suppress tumor growth in vivo of FRA-expressing tumors in rodent xenograft models. Toxicology studies in non-human primates found no evidence of toxicity with MORAb-003 at supra- pharmacological doses. This open-label, multiple-infusion, first-in-human, dose-escalation trial evaluates the safety, pharmacokinetics (PK), and anti-tumor activity of MORAb-003 in patients with platinum-resistant EOC. Methods: Sequential cohorts of patients received four weekly infusions at escalating dose levels of MORAb-003 from 12.5 mg/m 2 to 400 mg/m 2 . Eligible patients had platinum-resistant EOC, acceptable organ function, KPS = 70%, and measurable disease by GOG-RECIST criteria. A subset of subjects received a tracer dose of 111 In-labelled MORAb-003 and SPECT-CT and planar imaging. Human anti-human antibody (HAHA) and PK analyses were performed. Results: To date, 18 subjects have been dosed with up to 200 mg/m 2 . No dose limiting toxicity or significant related adverse events have been observed. Four subjects had rigors (2 grade 1) or fevers (3 grade 1, 1 grade 2) following the first infusion. Nine subjects have had radiologically stable disease, and 7 subjects have had stable or declining CA125. Two subjects have received extended therapy for an apparent clinical benefit. Radiolabelled tracer studies have demonstrated significant tumor uptake of labeled MORAb-003. The 400 mg/m 2 dose cohort is currently enrolling. Conclusions: The FRA-specific MAb MORAb-003 appears to be well tolerated in patients with EOC and may have activity in platinum-resistant patients. These results support further evaluation of the efficacy of MORAb-003 in a phase 2 study which is ongoing. [Table: see text]
PRIMARY PNEUMOCOCCIC PERITONITIS
Authors: A. Cuff
Journal: BMJ (1908)

APRIL i8,i I9p T9 calculated gotuunto depend upon the assumption that 1.8 per cent. of pmgen'5I AlW11Y In te plama bt +0.The cual values obtained in the control experi- ments of this series ranged between 1.46 and 2.16 per cent., a somewhat conslderable varlation.In an experiment of v. 8chroMter and his colleagues, a dog was exposed to +4.5 atmpheres for forty-five mtniuu, and the arterial blood yielded 9 2 per cent.,ofnitrogen as compared wlth a theoretical 9.9 pei cent.on he rOrmer awsumption.Bert's analyses are not strictly <c9ppassble w#th gige, a .hedid not maintain his animals
Small-Cell Carcinoma of the Lung: Therapeutic Management
Authors: RAYMOND B. WEISS
Journal: Annals of Internal Medicine (1978)

Although bronchogenic carcinoma generally remains a tumor resistant to treatment, marked progress in the therapy of the small-cell undifferentiated subtype has occurred in the past 5 years. Many aspects of its growth and metastatic spread are such that it is not satisfactorily treated surgically. However, it is sensitive to both radiation and a variety of chemotherapeutic agents. Use of these agents in combination seems to produce a greater antitumor effect than single drugs. The combination of radiation and chemotherapy results in marked tumor regressions. Untreated, this carcinoma has a very short median survival (2 months). Administration of current "aggressive" combination therapy regimens has resulted in median survivals of nearly 1 year with some patients still living 3 years after therapy.
Dissociation between<i>APOC3</i>variants, hepatic triglyceride content and insulin resistance
Authors: Julia Kozlitina, Eric Boerwinkle, Jonathan C. Cohen, Helen H. Hobbs
Journal: Hepatology (2010)

Nonalcoholic fatty liver disease (NAFLD) is an escalating health problem that is frequently associated with obesity and insulin resistance. The mechanistic relationship between NAFLD, obesity, and insulin resistance is not well understood. A nonsynonymous variant in patatin-like phospholipase domain containing 3 (rs738409, I148M) has been reproducibly associated with increased hepatic triglyceride content (HTGC) but has not been associated with either the body mass index (BMI) or indices of insulin resistance. Conversely, two sequence variants in apolipoprotein C3 (APOC3) that have been linked to hypertriglyceridemia (rs2854117 C > T and rs2854116 T > C) have recently been reported to be associated with both hepatic fat content and insulin resistance. Here we genotyped two APOC3 variants in 1228 African Americans, 843 European Americans and 426 Hispanics from a multiethnic population based study, the Dallas Heart Study and test for association with HTGC and homeostatic model of insulin resistance (HOMA-IR). We also examined the relationship between these two variants and HOMA-IR in the Atherosclerosis Risk in Communities (ARIC) study. No significant difference in hepatic fat content was found between carriers and noncarriers in the Dallas Heart Study. Neither APOC3 variant was associated with HOMA-IR in the Dallas Heart Study; this lack of association was confirmed in the ARIC study, even after the analysis was restricted to lean (BMI < 25 kg/m(2) ) individuals (n = 4399).Our data do not support a causal relationship between these two variants in APOC3 and either HTGC or insulin resistance in middle-aged men and women.
Investigation of Halothane
Authors: Leroy D. Vandam
Journal: JAMA (1963)

<h3>To the Editor:</h3> —We would like to call your attention and the attention ofThe Journal'sreaders to the recent reports of liver necrosis after anesthesia with halothane (Fluothane). It is by no means clear whether this anesthetic agent, which has been used in an estimated 6 million cases, is responsible for these or the rare previous reports of the complication, or whether other factors or drugs may be the cause. Possible interpretations and editorial comment appear, accompanying the reports of cases, in the<i>New England Journal of Medicine</i>, March 7, 1963, and<i>Anesthesiology</i>, January, 1963. Before conclusions can be drawn, carefully obtained statistical evidence will be needed. To meet this need, the National Research Council Committee on Anesthesia has appointed the undersigned<i>ad hoc</i>committee to prepare a prospective study in several institutions. In this study the use of halothane will be randomized according to the rigid statistical criteria
The Change of Serum HER2 Extra Cellular Domain Concentration Before and After Resection in Operable Gastric Cancer Patients in Japan; Consider Relations with Pathological HER2 Status by IHC and Fish
Authors: Taku Keisei, Tsuji Daiki, Watanabe Masaya, Suzuki Makoto, Miyato Hideyo, Ootani Kensuke, Yamaguchi Takamune, Maeda Masato, Ikematsu Yoshito, Hirai Mariko, Mizuno Shinichi, Takagi Masakazu
Journal: Annals of Oncology (2014)
A CASE OF RELAXATION OF THE PUBIC JOINTS DURING PREGNANCY.
Authors: JOSEPH B. DE LEE
Journal: JAMA (1902)

Mrs. B., age 39, XII para, four abortions, all deliveries normal. This pregnancy has advanced to the ninth month. Beginning at the sixth month, patient has had difficulty with the limbs and pain about the pelvis. The pains began on the right side over the sacro-iliac joint and have been getting worse there, also extending to the other sacro-iliac joint and to the pubis. Now the pain extends down the right leg, and all motions of the lower trunk and extremities are painful, being referred especially to the pelvic girdle, the pubis and the right side. Difficulty in walking has increased up to the present, locomotion at the present time being laborious and distressing. She can not cross the legs and all movements of the trunk and lower extremities are carried out with difficulty and pain. In sitting down or getting up, she has to use the hands and arms,
Comparison of neonatal management methods for very low birthweight babies.
Authors: G J Reynolds
Journal: BMJ (1980)

right thigh with discoloration and bruising.The superficial epithelium had sloughed off.Her lungs, spleen, and liver were congested.Str pyogenes was isolated from her skin and subcutaneous tissue, but not from her heart blood or spleen.Her right hip showed no underlying abnormality.This is another example of a patient with Str pyogenes infection who did not have a classical presentation.This case also emphasises the fulminating nature of the infection, as she died despite having been on appropriate high doses of benzylpenicillin for 20 hours.
Idiopathic Hemochromatosis
Authors: Marcel Simon, Michel Bourel, Bernard Genetet, Renée Fauchet
Journal: New England Journal of Medicine (1977)

We studied iron overloading and HLA types in 24 sibships of patients with idiopathic hemochromatosis, of which 15 had at least two subjects with overt forms. HLA types of 84 unrelated patients were also investigated. Among siblings there was a significant association (P less than 0.0001) between the presence of hemochromatosis and the possession of the same two HLA haplotypes. The fact that overt forms of hemochromatosis depend on the presence of two specific homologous chromosomes strongly supports a recessive mode of transmission for the overt disease. The haplotypic equilibrium demonstrated in the unrelated patients group is another supporting argument. The lod-score value (2.239 for theta = 0.005) in six families available for study further supports the conclusion that a hemochromatosis gene is closely linked to the HLA-A locus. HLA typing in families with hemochromatosis could provide a means of early detection of subjects at risk before appearance of any sign of iron overload.
EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts
Authors: Jessica Zucman, Olivier Delattre, Chantal Desmaze, Alan L. Epstein, Goran Stenman, Frank Speleman, Christopher D. M. Fletchers, Alain Aurias, Gilles Thomas
Journal: Nature Genetics (1993)
Recurrent Septicemia Associated with Congenital Deficiency of C2 and Partial Deficiency of Factor B and the Alternative Complement Pathway
Authors: Simon L. Newman, Larry B. Vogler, Ralph D. Feigin, Richard B. Johnston
Journal: New England Journal of Medicine (1978)

CONGENITAL deficiency of the second component of complement (C2) has been reported frequently in association with collagen-vascular diseases.1 , 2 Most patients with this disorder have not had serious infections.1 2 3 In the cases in which infections have been described, their pattern has been like that sometimes seen in persons without a demonstrable defect in the immune system,3 4 5 6 7 8 making it difficult to relate with certainty the C2 deficiency and the infection. In the two unrelated C2-deficient children described below, each having three episodes of septicemia, we found an associated partial deficiency of alternative pathway factor B and a functional abnormality of the alternative . . .
Spatial Separation of HLA-DM/HLA-DR Interactions within MIIC and Phagosome-Induced Immune Escape
Authors: Wilbert Zwart, Alexander Griekspoor, Coenraad Kuijl, Marije Marsman, Jacco van Rheenen, Hans Janssen, Jero Calafat, Marieke van Ham, Lennert Janssen, Marcel van Lith, Kees Jalink, Jacques Neefjes
Journal: Immunity (2005)
Abstract 1226: p53 signaling pathway acts as rescue mechanism to β1 integrin silencing in head and neck cancer cell line
Authors: Mi Ra Kim, Hyo Won Chang, Hyo Jung Kim, So Young Moon, Myung Jin Lee, MyungWoul Han, Seong Who Kim, Sang Yoon Kim
Journal: Cancer Research (2011)

Abstract β1 integrin's aberrant expression has implicated a cancer progression and resistance to cytotoxic therapy. Moreover, cancer cells gained epithelial mesenchymal transition (EMT) features were more resistant to the detachment-induced cell death. In this regard, we investigated the mechanism by which β1-Integrin governs cell viability and verified whether the signaling pathway is associated with EMT features. Cancer cell lines from head and neck cancer patients (AMC-HN3 and AMC-HN9) and well-known EMT cancer, MDA-MB231, were used in this study. To determine whether three cell lines reveal the epithelial EMT features, EMT markers such as Snail, vimentin, fibronectin and E-cadherin were evaluated by western blot analysis and immunofluroscence. To knockdown β1 integrin signal, β1 integrin small interfering RNA (siRNA) was transiently transfected into all cell lines. The cell viability was examined by looking at the results of propidium iodide staining, MTT assay, changes in the mitochondrial membrane potential and cell morphology. MDA-MB231 and AMC-HN9 cells possessed EMT features whereas AMC-HN3 cells were not shown EMT phenotype. β1 integrin silencing cell increased the sub G1 from 1.0% to 29.8%, increased the percentage of cells losing their mitochondrial membrane potential from 5.3% to 65.9% as well as the number of fragmented mitochondria in AMC-HN3 cells. In contrast, MDA-MB231 cells showed more resistance to silencing of β1 integrin, lower cell death rate from 0.6% to 9.6% and less changes in the mitochondrial membrane potential from 4.34% to 34.51%. Interestingly, AMC-HN9 cells showed complete resistance to β1 integrin blocking even though FAK phosphorylation signaling was blocked in AMC-HN9 cells, same as AMC-HN3 cells, which is a different response from typical EMT featured cells. When AMC-HN9 cells were treated to inhibit β1 integrin and p53 separately, it showed no response to changes in the cellular morphology, viability and apoptosis-related signal pathway; however, when it was given the combined β1 integrin and p53, apoptosis occurred in the cell line. In this study, acquisition of the EMT features in cancer cells presented resistance to the β1 integrin inhibition. In addition, the activation of p53-p21 signaling pathway provided resistance to detachment-induced apoptosis in head and neck cancer cell line with EMT features. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1226. doi:10.1158/1538-7445.AM2011-1226
Cost-Effectiveness of Percutaneous Coronary Intervention With Drug Eluting Stents Versus Bypass Surgery for Patients With Diabetes Mellitus and Multivessel Coronary Artery Disease
Authors: Elizabeth A. Magnuson, Michael E. Farkouh, Valentin Fuster, Kaijun Wang, Katherine Vilain, Haiyan Li, Jaime Appelwick, Victoria Muratov, Lynn A. Sleeper, Robin Boineau, Mouin Abdallah, David J. Cohen
Journal: Circulation (2013)

Studies from the balloon angioplasty and bare metal stent eras have demonstrated that coronary artery bypass grafting (CABG) is cost-effective compared with percutaneous coronary intervention (PCI) for patients undergoing multivessel coronary revascularization-particularly among patients with complex coronary artery disease or diabetes mellitus. Whether these results apply in the drug-eluting stent (DES) era is unknown.
Aneurysm of the main stem of the left coronary artery associated with aortic insufficiency and aneurysm of the ascending aorta. Report of a case with successful surgical repair.
Authors: A Leguerrier, M Bercot, A Piwnica
Journal: Thorax (1978)

The metabolism of bexarotene, a rexinoid recently approved in the United States for treatment of cutaneous T-cell lymphoma, was studied using liver slices from untreated rats and dogs, liver microsomes from untreated and pretreated rats, and pooled human liver microsomes. Metabolite profiles were examined in bile and plasma from rats and dogs, and plasma from humans treated with bexarotene. Four metabolites, racemic 6-hydroxy-bexarotene, racemic 7-hydroxy-bexarotene, 6-oxo-bexarotene, and 7-oxo-bexarotene, were synthesized and their binding to, and transactivation of retinoid receptors were examined. Qualitatively similar metabolite profiles were observed in the microsomal and liver slice extracts; the predominant metabolites were 6-hydroxy-bexarotene and glucuronides of parent or hydroxylated metabolites. Pretreatment of rats with bexarotene induced hepatic microsomal bexarotene metabolism. The hydroxy and oxo metabolites were observed in plasma of rats, dogs, and humans treated with bexarotene and 6-hydroxy-bexarotene was a major circulating metabolite. The oxidative metabolites were more abundant relative to parent in plasma from humans than from rat or dog. The predominant biliary metabolites in rat and dog were bexarotene acyl glucuronide and a glucuronide of oxidized bexarotene, respectively. Since bexarotene elimination is primarily biliary in these species, these metabolites represent the main bexarotene metabolites in rats and dogs. The binding of synthetic metabolites to retinoid receptors was much reduced relative to parent compound. The metabolites exhibited minimal activity in transactivating retinoic acid receptors and had reduced activity at retinoid X receptors relative to bexarotene. Thus, while there is substantial systemic exposure to the oxidative metabolites of bexarotene, they are unlikely to elicit significant retinoid receptor activation following bexarotene administration.
Keelmen Heaving in Coals by Moonlight
Authors: M. Therese Southgate
Journal: JAMA (2007)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Exercise following a sport induced concussion
Authors: B Gall, W S Parkhouse, D Goodman
Journal: British Journal of Sports Medicine (2004)

Objective: To determine if an athlete’s capacity to perform exercise is impaired following concussion and whether this would be reflected by an altered heart rate response. Methods: Of the 14 concussed athletes, nine missed playing time as a direct result of their concussion and five did not. The concussed athletes performed an exercise protocol on a cycle ergometer within 72 hours of being asymptomatic at rest and a second test at 5 days following the previous assessment. Matched controls (n = 14) were tested using the same time line. The exercise protocol consisted of a 2 minute warm up, 10 minute, low−moderate intensity, steady state exercise session, and a high intensity interval protocol. The interval protocol consisted of a 40 second high intensity bout, followed by a 40 second rest period. This protocol continued until the participant had reached volitional fatigue. Results: The number of exercise bouts completed was not significantly different from their matched controls. However, concussed athletes who missed playing time had a significantly higher heart rate during the steady state exercise session. During this same period, they also exhibited a greater rise in heart rate over time. Conclusion: These findings indicate that exercise capacity is unaffected in concussed athletes who are asymptomatic at rest. However, their heart rate response to submaximal exercise is increased.
Malonyl-CoA: the regulator of fatty acid synthesis and oxidation
Authors: Daniel W. Foster
Journal: Journal of Clinical Investigation (2012)

In the catabolic state with no food intake, the liver generates ketones by breaking down fatty acids. During the nocturnal fast or longer starvation periods, this protects the brain, which cannot oxidize fatty acids. In 1977, we published a study in the JCI noting the surprising realization that malonyl-CoA, the substrate of fatty acid synthesis, was also an inhibitor of fatty acid oxidation. Subsequent experiments have borne out this finding and furthered our understanding of molecular metabolism.
Remarks on Ulcerative Endocarditis, or Multiple Embolism
Authors: J. S. Bristowe
Journal: BMJ (1880)

Ohidene was administered with the gas-and ether-inhaler.He did not respire regularly at first; but he never coughed, and was not ob- ser-ved to swallow.After twelve or fourteen respirations, he talked, and commenced to struggle.The face-piece was then removed for a little distance from the face, to allow him to breathe some fresh air.The struggling and convulsive movement which followed interfered with the precise observation of the state of the pulse; when these had ceased, there was hardly any pulse, and it soon disappeared; but he continued to breathe ten or twelve times in a satisfactory manner, and then a pause was noticed between the respirations.His head was im- mediately extended backward and downward over the edge of the bed, and the tongue drawn forward, whilst the feet were raised, and artificial respiration commenced.This, in about a minute, restored him so far as to cause him to try to speak in an indistinct manner, as a patient often does just before waking up.The pulse became distinct, all danger seemed past, and he was again placed in the position for operating.In doing this, he seemed to raise his head voluntarily, and some more of the anaesthetic was about to be given, when the pulse was again noticed to be failing.Without loss of time, the artificial respiration was recommenced as before, and, during the first three minutes, there were several natural gasping inspirations, but the pulse was never felt again.The case becoming desperate, an opening was made through the crico-thyroid membrane into the larynx, and a silver tube introduced.Air was blown through the laryngeal tube, during artificial inspirations, for three-quarters of an hour, after which it became evident that further attempts were useless.The post mortemt examination, made by Mr. Samuel Lloyd of Blooms- bury, reveaJed a large flabby heart, with the usual amount of fat on it; the substance seen on section, of pale tint mottled with yellow, having the ordinary appearance of fatty degeneration.The lungs were a little emphysematous, and congested posteriorly, but fairly crepitant.The spleen was friable; other organs healthy; the liver rather large.The heart was carefully examined 4y Dr. Crosby, who wrote the following notes of it."The apex of the heart, including the extremities of both ventricles, was covered with a layer of fat five-eighths of an inch in thickness, which mingled with the muscular wall so as to render it difficult to define where one ceased and the other began.The microscope showed the muscular tissue at this part to have undergone extensive degeneration, whole fibres consisting of strings of fat-globules, displacing the true sarcous elements.At other portions, where to the unaided eye the muscle appeared fairly healthy, abundant deposits of oil-globules existed."