tbuckley/cabot-search huggingface dataset:
Dying for a drink
Authors: T. Foster
Journal: BMJ (2001)

Background/Aim: It has been shown in many studies that expression of pyruvate kinase (PK) enzyme plays a key role during cellular metabolism. There is evidence that cancer cells manifesting very dynamic proliferation may control their division in various mechanisms, i.a. by expression of PKM2 isoform. The exact role of PKM2 in ovarian cancer (OC) cells and cancer associated fibroblasts (CAFs) have not been elucidated. Materials and Methods: The present study was focused on analysis of PKM2 expression in cancer cells and CAFs in 97 OC cases, mostly of serous histological type. Moreover, relationships between expression of PKM2 and proliferation (Ki-67; MCM-2, -3, -7; cyclin D1), vascular (CD31, D2-40) and mesenchymal (Vim and αSMA) markers as well as receptors (ER, PR, HER2, EGFR) were examined. All observations were evaluated in regard to available clinicopathological data. Results: The expression of PKM2 was disclosed only in cytoplasm of OC cells. No statistically significant correlation between PKM2 and tested markers was found. In regard to available clinicopathological data only an increasing trend of PKM2 expression with increasing grade of histological malignancy G was found (p=0.07). Conclusion: Due to achieved results concerning expression of PKM2 there is a lack of evidence for its diagnostic and prognostic usage in OC.
Older women less likely to receive chemotherapy for breast cancer
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

The older a woman is, the less likely she is to receive recommended chemotherapy after breast cancer surgery. This is a finding of a new study reported in the Annals of Internal Medicine (2003:138;90-7), in which the authors say there is “a clear divergence between consensus recommendations and clinical practice.”

The journal editors say (in the “Editors' notes” box accompanying the article): “Since only a minority of postmenopausal women receive adequate treatment for breast cancer, many unnecessary deaths could probably be prevented by following the National Institutes of Health guidelines.”

The study used data from the state-wide, population based New Mexico tumour registry, …
A single centre experience of short course treatment for chronic hepatitis c genotype 2/3 infection in patients with rapid viral response
Authors: S. D. Jafri, C. Puli, L. Hodge-Johnson, C. L. Ch'ng
Journal: Gut (2011)

<h3>Introduction</h3> There is increasing incidence of chronic hepatitis C in Wales with estimated 12 000 individuals infected with the virus giving a prevalence of 0.4% of the population. Welsh BBV Action Plan expects more patients to be treated each year. The treatment is associated with significant side-effects and cost implications. The authors report their experience in the treatment of hepatitis C genotype 2/3 patients. <h3>Methods</h3> All patients treated in Singleton Hospital were prospectively audited between January 2007 and December 2009. All patients were genotyped and selected patients had liver biopsies. Hepatitis C PCR/viral load was checked at 4 weeks and 6 months post-treatment. Patients with rapid virological response (RVR), that is, negative PCR at 4 weeks were offered 16 weeks combination therapy unless they are cirrhotic. <h3>Results</h3> 147 patients were treated from January 2007 till August 2010. 83 patients were genotype1, four genotype 4, six genotype 2, 50 genotype 3 while four were unknown genotypes. Of the 44 patients with genotype 2/3 who underwent treatment between January 2007 and December 2009, 22 (6 genotype 2 and 16 genotype 3) were treated with 16 weeks combination therapy following RVR. 3 of these 22 lost to follow-up, one stopped treatment because of serious adverse event and 18 patients showed sustained viral response (SVR) at 6 months post-treatment giving an SVR rate of 81% (18/22). Of the other 22 patients (20 without RVR and 2 with RVR but cirrhosis) were given 24 weeks of treatment, 1 lost follow-up, 12 patients achieved SVR, 8 did not while SVR couldn9t be done in 1 patient despite of all efforts; giving SVR rate in this cohort of 55% (12/22). <h3>Conclusion</h3> In their experience, 16 weeks short course combination peginterferon and ribavirin is effective for hepatitis C genotype 2/3 patients. Patients with RVR are associated with a significant better outcome (SVR) compared to those without, that is, 81% versus 50%. Short course treatment will reduce treatment and monitoring costs and duration of side effects. It also allows more patients to be treated each year.
Evoked Axonal Oxytocin Release in the Central Amygdala Attenuates Fear Response
Authors: H. Sophie Knobloch, Alexandre Charlet, Lena C. Hoffmann, Marina Eliava, Sergey Khrulev, Ali H. Cetin, Pavel Osten, Martin K. Schwarz, Peter H. Seeburg, Ron Stoop, Valery Grinevich
Journal: Neuron (2012)
CXCR2 Expression in Tumor Cells Is a Poor Prognostic Factor and Promotes Invasion and Metastasis in Lung Adenocarcinoma
Authors: Pierre Saintigny, Erminia Massarelli, Steven Lin, Young-Ho Ahn, Yulong Chen, Sangeeta Goswami, Baruch Erez, Michael S. O'Reilly, Diane Liu, J. Jack Lee, Li Zhang, Yuan Ping, Carmen Behrens, Luisa M. Solis Soto, John V. Heymach, Edward S. Kim, Roy S. Herbst, Scott M. Lippman, Ignacio I. Wistuba, Waun Ki Hong, Jonathan M. Kurie, Ja Seok Koo
Journal: Cancer Research (2012)

CXCR2 in non-small cell lung cancer (NSCLC) has been studied mainly in stromal cells and is known to increase tumor inflammation and angiogenesis. Here, we examined the prognostic importance of CXCR2 in NSCLC and the role of CXCR2 and its ligands in lung cancer cells. The effect of CXCR2 expression on tumor cells was studied using stable knockdown clones derived from a murine KRAS/p53-mutant lung adenocarcinoma cell line with high metastatic potential and an orthotopic syngeneic mouse model and in vitro using a CXCR2 small-molecule antagonist (SB225002). CXCR2 protein expression was analyzed in tumor cells from 262 NSCLC. Gene expression profiles for CXCR2 and its ligands (CXCR2 axis) were analyzed in 52 human NSCLC cell lines and 442 human lung adenocarcinomas. Methylation of CXCR2 axis promoters was determined in 70 human NSCLC cell lines. Invasion and metastasis were decreased in CXCR2 knockdown clones in vitro and in vivo. SB225002 decreased invasion in vitro. In lung adenocarcinomas, CXCR2 expression in tumor cells was associated with smoking and poor prognosis. CXCR2 axis gene expression profiles in human NSCLC cell lines and lung adenocarcinomas defined a cluster driven by CXCL5 and associated with smoking, poor prognosis, and RAS pathway activation. Expression of CXCL5 was regulated by promoter methylation. The CXCR2 axis may be an important target in smoking-related lung adenocarcinoma.
Ambient Air Pollution and Pregnancy Outcomes: A Review of the Literature
Authors: Radim J. Šrám, Blanka Binková, Jan Dejmek, Martin Bobak
Journal: Environmental Health Perspectives (2005)

Over the last decade or so, a large number of studies have investigated the possible adverse effects of ambient air pollution on birth outcomes. We reviewed these studies, which were identified by a systematic search of the main scientific databases. Virtually all reviewed studies were population based, with information on exposure to air pollution derived from routine monitoring sources. Overall, there is evidence implicating air pollution in adverse effects on different birth outcomes, but the strength of the evidence differs between outcomes. The evidence is sufficient to infer a causal relationship between particulate air pollution and respiratory deaths in the postneonatal period. For air pollution and birth weight the evidence suggests causality, but further studies are needed to confirm an effect and its size and to clarify the most vulnerable period of pregnancy and the role of different pollutants. For preterm births and intrauterine growth retardation (IUGR) the evidence as yet is insufficient to infer causality, but the available evidence justifies further studies. Molecular epidemiologic studies suggest possible biologic mechanisms for the effect on birth weight, premature birth, and IUGR and support the view that the relation between pollution and these birth outcomes is genuine. For birth defects, the evidence base so far is insufficient to draw conclusions. In terms of exposure to specific pollutants, particulates seem the most important for infant deaths, and the effect on IUGR seems linked to polycyclic aromatic hydrocarbons, but the existing evidence does not allow precise identification of the different pollutants or the timing of exposure that can result in adverse pregnancy outcomes.
Absorption studies in patients six to 10 years after construction of ileostomy reservoirs.
Authors: L O Nilsson, H Andersson, L Hulten, R Jagenburg, N G Kock, H E Myrvold, B Philipson
Journal: Gut (1979)

The absorption of fat, bile salts, and vitamin B12 was studied in 14 proctocolectomised patients six to 10 years after construction of a continent ileostomy. All patients were in excellent health and displayed no signs of malnutrition. Schilling test disclosed subnormal absorption of vitamin B12 in one patient and borderline values in five. Faecal loss of bile acid was increased in 12 patients and fat malabsorption occurred in two. Except for slightly pathological liver tests in two patients, routine laboratory tests, including plasma concentration of vitamin B12 and folic acid, were normal. There were no signs of sodium or potassium depletion.
The Incense Burner
Authors: Thomas B. Cole
Journal: JAMA (2011)

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
Terminal Differentiation of Cardiac and Skeletal Myocytes Induces Permissivity to AAV Transduction by Relieving Inhibition Imposed by DNA Damage Response Proteins
Authors: Jasmina Lovric, Miguel Mano, Lorena Zentilin, Ana Eulalio, Serena Zacchigna, Mauro Giacca
Journal: Molecular Therapy (2012)

Gene therapy vectors based on the adeno-associated virus (AAV) are extremely efficient for gene transfer into post-mitotic cells of heart, muscle, brain, and retina. The reason for their exquisite tropism for these cells has long remained elusive. Here, we show that upon terminal differentiation, cardiac and skeletal myocytes downregulate proteins of the DNA damage response (DDR) and that this markedly induces permissivity to AAV transduction. We observed that expression of members of the MRN complex (Mre11, Rad50, Nbs1), which bind the incoming AAV genomes, faded in cardiomyocytes at ~2 weeks after birth, as well as upon myoblast differentiation in vitro; in both cases, withdrawal of the cells from the cell cycle coincided with increased AAV permissivity. Treatment of proliferating cells with short-interfering RNAs (siRNAs) against the MRN proteins, or with microRNA-24, which is normally upregulated upon terminal differentiation and negatively controls the Nbs1 levels, significantly increased permissivity to AAV transduction. Consistently, delivery of these small RNAs to the juvenile liver concomitant with AAV markedly improved in vivo hepatocyte transduction. Collectively, these findings support the conclusion that cellular DDR proteins inhibit AAV transduction and that terminal cell differentiation relieves this restriction. Gene therapy vectors based on the adeno-associated virus (AAV) are extremely efficient for gene transfer into post-mitotic cells of heart, muscle, brain, and retina. The reason for their exquisite tropism for these cells has long remained elusive. Here, we show that upon terminal differentiation, cardiac and skeletal myocytes downregulate proteins of the DNA damage response (DDR) and that this markedly induces permissivity to AAV transduction. We observed that expression of members of the MRN complex (Mre11, Rad50, Nbs1), which bind the incoming AAV genomes, faded in cardiomyocytes at ~2 weeks after birth, as well as upon myoblast differentiation in vitro; in both cases, withdrawal of the cells from the cell cycle coincided with increased AAV permissivity. Treatment of proliferating cells with short-interfering RNAs (siRNAs) against the MRN proteins, or with microRNA-24, which is normally upregulated upon terminal differentiation and negatively controls the Nbs1 levels, significantly increased permissivity to AAV transduction. Consistently, delivery of these small RNAs to the juvenile liver concomitant with AAV markedly improved in vivo hepatocyte transduction. Collectively, these findings support the conclusion that cellular DDR proteins inhibit AAV transduction and that terminal cell differentiation relieves this restriction.
Increased bone marrow FDG uptake at PET/CT is not a sufficient proof of bone marrow involvement in diffuse large B-cell lymphoma
Authors: Hugo J.A. Adams, Thomas C. Kwee
Journal: American Journal of Hematology (2015)

We read with interest the article by Chen-Liang et al. 1 that was recently published in the Journal. Their study included 372 lymphoma patients and comprised a subgroup of 155 patients with diffuse large B-cell lymphoma (DLBCL) who underwent both 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) and unilateral bone marrow biopsy (BMB) of the iliac crest. Sensitivity of FDG-PET/CT and BMB were calculated using the combination of the two tests as reference standard. Bone marrow involvement was detected by BMB in 20 patients and by FDG-PET/CT in 22 patients. Sensitivity of BMB and FDG-PET/CT for the detection of bone marrow involvement in DLBCL was 62.5% and 65.6%, respectively. Chen-Liang et al. 1 concluded that BMB and FDG-PET/CT are complementary techniques for the assessment of bone marrow involvement. They recommend to perform bone marrow assessment first by means of FDG-PET/CT, and thereafter only perform BMB in case of either equivocal, diffuse, or negative bone marrow involvement at FDG-PET. Consequently, they suggest that BMB can be omitted in case of unequivocal bone marrow involvement at FDG-PET/CT. Although the results of the study by Chen-Liang et al. 1 underline the results of our previous study 2 that FDG-PET has a suboptimal sensitivity for the identification of bone marrow involvement in DLBCL, we cannot agree with their conclusion that bone marrow abnormalities at FDG-PET/CT can confidently designate advanced-stage disease. Increased focal FDG uptake in the marrow is not sufficient evidence to confirm bone marrow involvement. Benign or other malignant bone marrow lesions may also result in increased FDG uptake 3-6, and it is not possible to discriminate between these abnormalities without histological proof. This concern is reflected by the fact that although bone marrow involvement according to BMB has been established as an important adverse prognostic factor in DLBCL 7, this is not the case for FDG-PET/CT-based bone marrow involvement. Of the five studies that reported the prognostic value of bone marrow involvement at FDG-PET/CT in DLBCL 2, 8-11, four showed that FDG-PET/CT-based bone marrow status did not have any prognostic value at all 2, 8-10. These observations suggest that false-positive FDG-PET/CT results occur in a considerable proportion of patients with DLBCL and that increased FDG uptake of the marrow is not sufficient evidence to designate advanced-stage disease. In conclusion, multiple studies have shown that, unlike BMB, FDG-PET/CT-based bone marrow status has no prognostic value at all in DLBCL. The absence of prognostic implications of bone marrow involvement detected by FDG-PET/CT strongly suggests a considerable proportion of false-positive FDG-PET/CT results in patients with DLBCL. Hugo J.A. Adams*, Thomas C. Kwee Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
Localization of transglutaminase 1 mRNA in normal and psoriatic epidermis by non-radioactive in situ hybridization
Authors: K. NONOMURA, K. YAMANISHI, Y. HOSOKAWA, H. DOI, J. HIRANO, S. FUKUSHIMA, H. YASUNO
Journal: British Journal of Dermatology (1993)

We examined the expression of the transglutaminase 1 (TGase 1) gene in frozen sections of normal and psoriatic epidermis by means of non-radioactive in situ hybridization with digoxigenin-labelled cRNA probes. TGase 1 mRNA was expressed in the granular layer of normal epidermis, regardless of ortho- or hyperkeratosis. However, in psoriatic epidermis, TGase 1 mRNA was detected in the suprabasal spinous layer, but not in the subcorneal layer. These results indicate that TGase 1 gene expression is limited to the last stage of keratinization in normal epidermis and this regulation is disturbed in psoriasis.
Amyloid β Pathology in Alzheimer’s Disease and Schizophrenia
Authors: Dorota Religa, Hanna Laudon, Maria Styczynska, Bengt Winblad, Jan Näslund, Vahram Haroutunian
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Severe cognitive impairment is common in elderly patients with schizophrenia. Alzheimer's disease is the main cause of dementia among the elderly. Biochemical and genetic studies suggest that amyloid β-peptide is central in Alzheimer's disease. The authors examined the possible involvement of amyloid β-peptide in cognitive impairment in schizophrenia. METHOD: Specific antibodies against two major forms of amyloid β-peptide, Aβx-40 and Aβx-42, were used in sandwich enzyme-linked immunosorbent assays to determine the levels of amyloid β-peptide in postmortem brain samples from Alzheimer's disease patients (N=10), normal elderly comparison subjects (N=11), and schizophrenia patients with (N=7) or without (N=26) Alzheimer's disease. RESULTS: The levels of amyloid β-peptide were highest in the Alzheimer's disease patients, followed by the patients with schizophrenia and comparison subjects. The mean Aβx-42 level in the schizophrenia patients without Alzheimer's disease was similar to that in the comparison subjects, but the level in the schizophrenia patients with Alzheimer's disease was significantly higher than in those without Alzheimer's disease or the comparison subjects. The Aβx-42 level in the schizophrenia patients with Alzheimer's disease was significantly lower than the level in the Alzheimer's disease cohort. CONCLUSIONS: In contrast to elderly schizophrenia patients with Alzheimer's disease pathology, those without Alzheimer's disease had amyloid β-peptide levels that were not significantly different from those of normal subjects; hence amyloid β-peptide does not account for the cognitive deficits in this group. These results suggest that the causes of cognitive impairment in "pure" schizophrenia are different from those in Alzheimer's disease.
Modulation of LIGHT-HVEM Costimulation Prolongs Cardiac Allograft Survival
Authors: Qunrui Ye, Christopher C. Fraser, Wei Gao, Liqing Wang, Samantha J. Busfield, Chichung Wang, Yubin Qiu, Anthony J. Coyle, Jose-Carlos Gutierrez-Ramos, Wayne W. Hancock
Journal: The Journal of Experimental Medicine (2002)

LIGHT (TNFSF14), a tumor necrosis factor superfamily member expressed by activated T cells, binds to herpes virus entry mediator (HVEM) which is constitutively expressed by T cells and costimulates T cell activation in a CD28-independent manner. Given interest in regulating the effector functions of T cells in vivo, we examined the role of LIGHT-HVEM costimulation in a murine cardiac allograft rejection model. Normal hearts lacked LIGHT or HVEM mRNA expression, but allografts showed strong expression of both genes from day 3 after transplant, and in situ hybridization and immunohistology-localized LIGHT and HVEM to infiltrating leukocytes. To test the importance of LIGHT expression on allograft survival, we generated LIGHT−/− mice by homologous recombination. The mean survival of fully major histocompatibility complex–mismatched vascularized cardiac allografts in LIGHT−/− mice (10 days, P &amp;lt; 0.05) or cyclosporine A (CsA)-treated LIGHT+/+ mice (10 days, P &amp;lt; 0.05) was only slightly prolonged compared with LIGHT+/+ mice (7 days). However, mean allograft survival in CsA-treated LIGHT−/− allograft recipients (30 days) was considerably enhanced (P &amp;lt; 0.001) compared with the 10 days of mean survival in either untreated LIGHT−/− mice or CsA-treated LIGHT+/+ controls. Molecular analyzes showed that the beneficial effects of targeting of LIGHT in CsA-treated recipients were accompanied by decreased intragraft expression of interferon (IFN)-γ, plus IFN-γ–induced chemokine, inducible protein-10, and its receptor, CXCR3. Treatment of LIGHT+/+ allograft recipients with HVEM-Ig plus CsA also enhanced mean allograft survival (21 days) versus wild-type controls receiving HVEM-Ig (mean of 7 days) or CsA alone (P &amp;lt; 0.001). Our data suggest that T cell to T cell–mediated LIGHT/HVEM-dependent costimulation is a significant component of the host response leading to cardiac allograft rejection.
THE USE OF HEROIN AFTER ABDOMINAL OPERATIONS: A WARNING
Authors: A. E. M. Woolf
Journal: BMJ (1929)

MEDTAI.JoL u 499 occasioni she reported herself as free from tr ouble witli hIer legs, and asked for a tonic.-Thepatient declared ilhat she had derived muchl relief from the local applicationi of miethyl salicylate ointlment.Cas,e 7.-A malried womani, aged 55, constulted uis for " tender lumps on1 her legs."She complained of niot feelinig wvell, bht, apart, fromn slight manaemia 'and -the coinditioni of hler legs, she appear-ed to us to be quiite well.Ourl usual treatment, was pi-e- scribed, and wlheni she reported aoaini in a week's timrie she, was mutclh imp roved.