tbuckley/cabot-search huggingface dataset:
Bispecific T-cells Expressing Polyclonal Repertoire of Endogenous γδ T-cell Receptors and Introduced CD19-specific Chimeric Antigen Receptor
Authors: Drew C Deniger, Kirsten Switzer, Tiejuan Mi, Sourindra Maiti, Lenka Hurton, Harjeet Singh, Helen Huls, Simon Olivares, Dean A Lee, Richard E Champlin, Laurence JN Cooper
Journal: Molecular Therapy (2013)

Even though other γδ T-cell subsets exhibit antitumor activity, adoptive transfer of γδ Tcells is currently limited to one subset (expressing Vγ9Vδ2 T-cell receptor (TCR)) due to dependence on aminobisphosphonates as the only clinically appealing reagent for propagating γδ T cells. Therefore, we developed an approach to propagate polyclonal γδ T cells and rendered them bispecific through expression of a CD19-specific chimeric antigen receptor (CAR). Peripheral blood mononuclear cells (PBMC) were electroporated with Sleeping Beauty (SB) transposon and transposase to enforce expression of CAR in multiple γδ T-cell subsets. CAR(+)γδ T cells were expanded on CD19(+) artificial antigen-presenting cells (aAPC), which resulted in >10(9) CAR(+)γδ T cells from <10(6) total cells. Digital multiplex assay detected TCR mRNA coding for Vδ1, Vδ2, and Vδ3 with Vγ2, Vγ7, Vγ8, Vγ9, and Vγ10 alleles. Polyclonal CAR(+)γδ T cells were functional when TCRγδ and CAR were stimulated and displayed enhanced killing of CD19(+) tumor cell lines compared with CAR(neg)γδ T cells. CD19(+) leukemia xenografts in mice were reduced with CAR(+)γδ T cells compared with control mice. Since CAR, SB, and aAPC have been adapted for human application, clinical trials can now focus on the therapeutic potential of polyclonal γδ T cells.
A flagella-less mutant of Borrelia burgdorferi. Structural, molecular, and in vitro functional characterization.
Authors: A Sadziene, D D Thomas, V G Bundoc, S C Holt, A G Barbour
Journal: Journal of Clinical Investigation (1991)

A nonmotile mutant of Borrelia burgdorferi, the etiologic agent of Lyme disease, was isolated and characterized. The mutant was compared with the wild-type predecessor as well as with a motile back-revertant of the same genetic background. The mutant lacked, by morphologic, biochemical, and immunologic criteria, the major structural protein of flagella, flagellin. This mutation was not associated with major DNA rearrangements or with failure of transcription. An apparent consequence of a loss of flagella was reduced ability to penetrate human endothelial cell layers in vitro. In another assessment of functional significance, the flagella-less mutant was equal if not superior to flagella-bearing, isogenic isolates when examined in an enzyme-linked immunosorbent assay for anti-B. burgdorferi antibodies in the sera of Lyme disease patients. These studies of a mutant, the first among pathogenic Borrelia spp. to be characterized, indicate that the flagellum and motility it confers play a role in B. burgdorferi's invasion of human tissues. A flagella-less B. burgdorferi may be useful as the basis of a more specific immunoassay and a vaccine for protection against Lyme disease.
Ventilatory responses to passive leg motion in children with congenital central hypoventilation syndrome.
Authors: D Gozal, C L Marcus, S L Ward, T G Keens
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

During exercise, children with congenital central hypoventilation syndrome (CCHS) demonstrate coupling of VE to exercise load, despite the absence of a VE response to changes in FICO2. To assess the effect of movement on VE, we studied six CCHS patients and six matched controls during passive motion in a motor-driven ergocycle at pedaling frequencies (PF) of 6 to 60 rpm. VE, VO2, VCO2, VT, heart rate, respiratory rate, SPO2, and PETCO2 were measured. During steady-state conditions, VE was constant at PF of 0 to 30 rpm, but increased at PF > or = 40 rpm in both controls and CCHS patients (p < 0.005). The increase in respiratory rate in CCHS patients was greater than in controls (p < 0.05) whereas VT increased similarly in both groups. At 60 rpm, VO2 increased in both groups, but VE/VO2 and VE/VCO2 increased in the CCHS patients and remained constant in the controls (P < 0.03; p < 0.04). From PF of 0 to 60, PETCO2 decreased from 47 +/- 7 to 41 +/- 6 mm Hg in the CCHS patients (p < 0.001) but remained unchanged in the controls (38 +/- 3 mm Hg; p = NS). An analysis of on-transient responses at 60 rpm revealed that VE increased immediately with the first breath after onset of motion in both groups, and that comparable differences in ventilatory patterns persisted in the two groups. We conclude that passive leg motion at PF > or = 40 increases VE in both CCHS patients and controls. In controls, VE was tightly coupled to VO2 and VCO2. However, in CCHS patients, passive leg motion elicited normalization of PETCO2.
Interleukin 1 in ulcerative colitis.
Authors: P Gionchetti, M Campieri, A Belluzzi, P Boni, C Brignola, H Ferretti, P Iannone, M Miglioli, L Barbara
Journal: Gut (1991)

Whether the plasma concentration of beta endorphin was increased in hepatic cirrhosis like that of smaller opioid peptides methionine enkephalin and leucine enkephalin was determined. Its concentration in chronic renal failure was also measured. Plasma beta endorphin was not significantly raised in cirrhotic patients with or without ascites (medians 5.2 pmol/l and 4.7 pmol/l respectively) compared with disease control subjects (4.9 pmol/l) and healthy control subjects (4.9 pmol/l). In contrast, the peptide was increased 2.5 fold (p less than 0.001) in chronic renal failure (12.4 pmol/l) and was found in many of these patients9 urine. The data are compatible with the hypothesis that the liver may play an important role in the elimination of opioid peptides of octapeptide size or less but not the larger peptides such as beta endorphin.
Psychotic Reactions During Therapy With Pargyline
Authors: Alton I. Sutnick, Laurence B. Weiss, Peter D. Schindler, Louis A. Soloff
Journal: JAMA (1964)

PARGYLINE HYDROCHLORIDE, a nonhydrazine monamine oxidase inhibitor, has been reported by many investigators, including ourselves, as an effective antihypertensive agent.<sup>1,2</sup>Side effects are said to be relatively minor, with the most significant problem that of postural hypotension. Nervousness has been rather consistently numbered among the side effects. As part of a clinical evaluation of pargyline, we have treated 33 patients with this drug. Three, reported herein, developed psychotic episodes which disappeared upon cessation of therapy. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 42-year-old white male was admitted to Temple University Hospital on Jan 24, 1963, for evaluation of hypertension of at least two years' duration. There were no symptoms attributable to his hypertension. He has had a heart murmur, known since 1941, when he was rejected for military service. There is no history of rheumatic fever, but he had malaria two times in childhood. He is a rather introspective person,
Paediatricians criticise college over Southall debacle
Authors: Caroline White
Journal: BMJ (2001)

Three paediatricians close to the unfolding of the various inquiries into the work of two recently suspended doctors, Professor David Southall and Dr Martin Samuels, have criticised the handling of the affair and those involved in its prosecution.

In an editorial in the Archives of Disease in Childhood they have called for the establishment of an independent national panel for research integrity to adjudicate on future investigations. The editorial was posted on the journal's website last Friday, but later removed for possible changes.

The editorial was written in the wake of the reinstatement of Professor Southall to his post …
Compromised Ox40 Function in Cd28-Deficient Mice Is Linked with Failure to Develop Cxc Chemokine Receptor 5–Positive Cd4 Cells and Germinal Centers
Authors: Lucy S.K. Walker, Adam Gulbranson-Judge, Sarah Flynn, Thomas Brocker, Chandra Raykundalia, Margaret Goodall, Reinhold Förster, Martin Lipp, Peter Lane
Journal: The Journal of Experimental Medicine (1999)

Mice rendered deficient in CD28 signaling by the soluble competitor, cytotoxic T lymphocyte–associated molecule 4–immunoglobulin G1 fusion protein (CTLA4-Ig), fail to upregulate OX40 expression in vivo or form germinal centers after immunization. This is associated with impaired interleukin 4 production and a lack of CXC chemokine receptor (CXCR)5 on CD4 T cells, a chemokine receptor linked with migration into B follicles. Germinal center formation is restored in CTLA4-Ig transgenic mice by coinjection of an agonistic monoclonal antibody to CD28, but this is substantially inhibited if OX40 interactions are interrupted by simultaneous injection of an OX40-Ig fusion protein. These data suggest that CD28-dependent OX40 ligation of CD4 T cells at the time of priming is linked with upregulation of CXCR5 expression, and migration of T cells into B cell areas to support germinal center formation.
Are internet service providers responsible for online suicide pacts?
Authors: Q. Cheng
Journal: BMJ (2011)

Information that might encourage suicide is widespread on the internet, and a recent study describes this situation in mainland China ( J Clin Psychiatry 2011;72:313-9, doi:10.4088/JCP.09m05440blu). The Chinese government has shown its willingness to combat so called inappropriate information online, but it is unclear whether information that might encourage suicide is categorised as such inappropriate information.

According to the Chinese media, the first civil case in China where parents sued an internet service provider over their son’s suicide took place in October 2010 in Lishui City, Zhejiang Province ( Beijing Times 2010 Dec 4: 14). The plaintiff’s son, known as A, a 20 year old university student, responded to a suicide pact invitation made by B, a 22 year old university student, through QQ Groups, China’s most popular instant messaging service. In June 2010 the two tried to commit suicide together by carbon monoxide poisoning using charcoal …
Acute myocardial infarction in women: survival analysis in first six months
Authors: P Wilkinson, K Laji, K Ranjadayalan, L Parsons, A D Timmis
Journal: BMJ (1994)

Objective : To examine the influence that being female has on the outcome of acute myocardial infarction. Design : Observational follow up study. Setting : London district general hospital. Patients : 216 women and 607 men with acute myocardial infarction admitted to a coronary care unit from 1 January 1988 to 31 December 1992. Main outcome measures : All cause mortality and recurrent ischaemic events in the first six months. Results : Event free survival (95% confidence interval) at six months was 63.3% (56.3% to 69.4%) in women and 76.1% (72.4% to 79.4%) in men, P<0.001. The difference was confined to the first 30 days but thereafter the hazard plots for women and men converged, with reduction of the hazard ratio from 2.36 (1.70 to 3.27) to 0.81 (0.44 to 1.48). Women were older, but their excess risk persisted after adjustment for age, other baseline variables, and indices of severity of infarction (hazard ratio 1.53 (1.09 to 2.15), P=0.015). Women tended to be treated with thrombolysis less commonly than men but the difference was small. Substantially fewer women than men, however, were discharged taking ß blockers (23.3% v 41.4%, P <0.001), and although additional adjustment for discharge treatment did not further reduce the point estimate of the hazard ratio (1.84 (0.89-3.83)), the 95% confidence interval was wide and statistical significance was lost. Conclusions : Women with acute myocardial infarction have a worse prognosis than men but the excess risk is confined to the first 30 days and is only party explained by age and other baseline variables. The tendency for women to receive less vigorous treatment than men must be remedied before gender can be considered to be an independent determinant of risk.
Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma
Authors: Josep M. Llovet, Margarita Sala, Lluís Castells, Yanette Suarez, Ramon Vilana, Lluís Bianchi, Carmen Ayuso, Víctor Vargas, Joan Rodés, Jordi Bruix
Journal: Hepatology (2000)

The aim of this randomized controlled trial was to assess the efficacy of interferon alfa-2b (IFN) for the treatment of advanced hepatocellular carcinoma (HCC). Fifty-eight patients with HCC who were not suitable for resection, transplantation, ethanol injection, or arterial embolization were stratified according to their Okuda stage and randomized to receive IFN (3 × 10 6 , 3 times a week, for 1 year) (n = 30) or symptomatic treatment (n = 28). Both groups were identical in terms of age, sex, performance status, presence of constitutional syndrome, Child-Pugh class, Okuda stage, multinodularity, portal thrombosis, and extrahepatic spread. Adhesion to IFN treatment was adequate in 27 patients, with a mean duration of treatment of 8 ± 3 months. However, IFN treatment was associated with side effects in 23 patients, leading to treatment discontinuation in 13 patients. Two of the 30 patients (6.6%) presented a partial response with greater than 50% size reduction and normalization of α-fetoprotein levels. The survival at 1 and 2 years according to intention to treat was not different between the 2 groups (58% and 38% vs. 36% and 12%, respectively, Breslow P = .19, log rank P = .14) and the absence of difference was maintained when dividing patients according to their Okuda stage. The probability of presenting tumor progression ( P = .17), or deterioration of Child-Pugh class ( P = .37), performance status ( P = .07), or Okuda stage ( P = .44) was not modified by IFN treatment. These results indicate that IFN is not properly tolerated in patients with cirrhosis and advanced HCC and that its administration prompts no benefit in terms of tumor progression rate and survival.
Hydroxyurea Administered Intermittently
Authors: Harvey J. Lerner
Journal: JAMA (1965)

THE SYNTHESIS of hydroxyurea (Hydrea) was reported in 1869 by Dresler and Stein.<sup>1</sup>In animal studies, Rosenthal et al<sup>2</sup>found that the compound produced anemia, severe leukopenia, and megaloblastic changes in the peripheral blood and bone marrow. Recently, this compound has been introduced into cancer chemotherapy. Tumor responses have been observed in squamous cell cancer, adenocarcinomas, melanomas, sarcomas, and chronic leukemia.<sup>3,4</sup> The greatest limiting factor in the use of hydroxyurea has been depression of bone marrow, primarily manifested as leukopenia.<sup>3</sup>The great majority of cancer chemotherapeutic agents (nonhormonal) produce depression in hematopoiesis. In addition to this depression, most agents produce other toxic reactions as noted by Hall.<sup>5</sup> The incidence of toxicity with hydroxyurea is 68% when 40 mg/kg of body weight per day, the originally suggested oral dose, is given. A twofold increase in that dose produces toxic reactions in all patients.<sup>3</sup> Each patient
Liver stiffness measurement predicts severe portal hypertension in patients with HCV‐related cirrhosis†‡
Authors: Francesco Vizzutti, Umberto Arena, Roberto G. Romanelli, Luigi Rega, Marco Foschi, Stefano Colagrande, Antonio Petrarca, Stefania Moscarella, Giacomo Belli, Anna Linda Zignego, Fabio Marra, Giacomo Laffi, Massimo Pinzani
Journal: Hepatology (2007)

Measurement of hepatic venous pressure gradient (HVPG) is a standard method for the assessment of portal pressure and correlates with the occurrence of its complications. Liver stiffness measurement (LSM) has been proposed as a noninvasive technique for the prediction of the complications of cirrhosis. In this study, we evaluated the ability of LSM to predict severe portal hypertension compared with that of HVPG in 61 consecutive patients with HCV-related chronic liver disease. A strong relationship between LSM and HVPG measurements was found in the overall population (r = 0.81, P < 0.0001). However, although the correlation was excellent for HVPG values less than 10 or 12 mm Hg (r = 0.81, P = 0.0003 and r = 0.91, P < 0.0001, respectively), linear regression analysis was not optimal for HVPG values ≥10 mm Hg (r2 = 0.35, P < 0.0001) or ≥12 mm Hg (r2 = 0.17, P = 0.02). The AUROC for the prediction of HVPG ≥10 and ≥12 mm Hg were 0.99 and 0.92, respectively and at LSM cutoff values of 13.6 kPa and 17.6 kPa, sensitivity was 97% and 94%, respectively. In patients with cirrhosis, LSM positively correlated with the presence of esophageal varices (P = 0.002), although no correlation between LSM and esophageal varices size was detected. The area under the ROC for the prediction of EV was 0.76 and at a LSM cutoff value of 17.6 kPa sensitivity was 90%. Conclusion: LSM represents a non-invasive tool for the identification of chronic liver disease patients with clinically significant or severe portal hypertension and could be employed for screening patients to be subjected to standard investigations including upper GI endoscopy and hemodynamic studies. (HEPATOLOGY 2007;45:1290–1297.)
Mutant p53 melanoma cell lines respond differently to CP-31398-induced apoptosis
Authors: C.K. Ho, G. Li
Journal: British Journal of Dermatology (2005)

Background p53, a commonly mutated gene in human cancers, participates in cell cycle arrest, DNA repair and apoptosis. A small pharmacological compound, CP‐31398, was found to have the ability to promote proper p53 protein folding, activate p53 transcription of downstream targets, and slow tumour growth in mice. Additionally, CP‐31398 was found to be able to convert mutant p53 to wild‐type conformation in several cell lines. Objectives To examine if CP‐31398 can revert all mutant p53 proteins to wild‐type function. Methods We studied a series of apoptotic responses to CP‐31398 in three melanoma cell lines varying in p53 mutation status. Results Upon a moderate dose of CP‐31398 treatment (15 µg mL−1), only the wild‐type p53 MMRU and the single p53 point mutation MeWo cells exhibited apoptosis. Another melanoma cell line, Sk‐mel‐110, containing multiple p53 mutations, did not exhibit apoptosis. Although CP‐31398 enhanced overall p53 protein level, its ability to promote proper folding of p53 protein was limited to CP‐31398‐sensitive MMRU and MeWo cells. These sensitive cells showed an increased Bax and PUMA transcription, altered mitochondrial membrane potential, followed by the release of cytochrome c, and cleaved caspase‐9 and caspase‐3. We also demonstrated that Apaf‐1 was not involved in CP‐31398‐mediated apoptosis. Conclusions Our results suggest that the ability of CP‐31398 to revert mutant p53 proteins to wild‐type conformation may be correlated to p53 mutational status. More studies are necessary, to further investigate the effect of CP‐31398 on mutant p53 and its potential applications as an anticancer agent.
UK patients can refuse to let their data be shared across networks
Authors: Michael Cross
Journal: BMJ (2005)

UK doctors will be expected to spend time in every consultation discussing with patients what information about them is shared across NHS computers. This is one of the implications of a “care record guarantee” that the Department of Health published this week to reassure patients and professionals about the confidentiality of data held in systems created for the NHS's national programme for IT (information technology).

Clinical data from GPs' computers and other NHS systems are due to be …
Radioiodine Scanning of the Thyroid
Authors: J??R??ME CLERC, MIREILLE IZEMBART, BRUNO BEROLATTI, AUB??NE L??GER, LIONEL BARRITAULT
Journal: Clinical Nuclear Medicine (1993)

CLERC, JÉRÔME M. D.; IZEMBART, MIREILLE PH. D.; BEROLATTI, BRUNO M. D.; LÉGER, AUBÈNE M. D.; BARRITAULT, LIONEL M. D., PH. D.
Resuscitation and Stabilization of the Critically Ill Child
Authors: James D. Fortenberry
Journal: JAMA (2010)

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
Heart valve replacement in the elderly.
Authors: A H de Bono, T A English, B B Milstein
Journal: BMJ (1978)

From January 1973 to December 1976, 70 operations for heart valve replacement were performed on 68 patients aged 65--75 years. These comprised 40 aortic valve replacements, 27 mitral valve replacements, and three aortic and mitral valve replacements. Three patients died within 30 days of operation (early mortality 4.3%), and five died 12 weeks to three years after operation. Four patients showed no improvement. The results were excellent or good in the remaining 56 patients. Valve replacemnt can restore to a useful independent life elderly patients who would otherwise be a burden on costly social and medical domiciliary services. The indications for valve surgery in the elderly should therefore be the same as in any other age group.
Public Attitudes Toward Autopsy, Organ Donation, and Dissection
Authors: Vlasta Balić
Journal: JAMA (1995)

<h3>To the Editor.</h3> —The Swedish survey comparing public attitudes toward autopsy, organ donation, and anatomical dissection<sup>1</sup>showed that 80% or more of the sample would accept autopsy of themselves or of close relatives and that more than 60% were willing to donate their own organs. We have recently completed a similar survey (using written questionnaires) in Split, which is the academic and hospital center of southern Croatia and a town of about 300 000 inhabitants in Dalmatia on the Adriatic Coast. Since our data were not quite similar to those seen in Northern Europe, we report the main results in Table 1. While younger Swedish people (younger than 29 years) are more likely to agree to organ donation and to autopsy than those older than 60 years, 48% of younger Croatians were uncertain about the issue and 53% of the older people polled responded that they could not make
Tubal Pregnancy at About Two Weeks.
Authors: D. S. Lamb
Journal: JAMA (1898)

Washington, D. C., Sept. 27, 1898. <h3>To the Editor:</h3> —The report of the case of tubal pregnancy with rupture at about the fifth week, by Dr. J. E. Cowles of Los Angeles, Cal., in theJournalof September 17, recalls a case of early pregnancy in which I made a postmortem examination April 4, 1893, on the wife of a physician who had suddenly died. She was 28 years old and had been married ten months. Her menses had recurred regularly, the last period being about the middle of March and unusually profuse. March 30 there was a show of blood by the vagina, two weeks after cessation of the last flow; April 2, sudden nausea, vomiting and tendency to collapse but no pain. Death next day, about twenty-four hours after these symptoms appeared. The postmortem examination showed a general bloodless condition, and a large quantity of blood and clots