tbuckley/cabot-search huggingface dataset:
Abstract 762: Atherosclerosis Regression Promoted By An LXR Agonist Is Dependent On The Chemokine Receptor CCR7
Authors: Jonathan E Feig, Ines Pineda-Torra, Raanan Shamir, Victor A Joaquin, Lisa S Grauer, Michael J Garabedian, Edward A Fisher
Journal: Circulation (2007)

We have developed a transplantation-based mouse model of atherosclerosis regression by allowing plaques to form in apoE−/ − mice, then changing the plaque’s plasma environment from hyperlipidemia to normolipidemia. In this model, we reported emigration of plaque foam cells to regional and systemic lymph nodes after 3 days in the regression environment (Llodrá et al. PNAS 2004). This emigration required the expression of the chemokine receptor CCR7 on the foam cells and was associated with up-regulation of their LXR mRNA (Trogan, Feig et al. PNAS 2006). Because the human and murine promoters have LXREs, we hypothesized that LXR was a regulator of CCR7. Using a murine model of immature DCs, D2.4 cells, we found that CCR7 expression is increased 8 –9X upon LXR activation by the agonist T0901317 (T09). Importantly, this increase is dependent on CCR7 gene transcription, because pre-treatment with actinomycin D abolished the observed response. When siRNA to LXR alpha and LXR beta was used in conjunction with T09, CCR7 gene expression was significantly blunted to only 2X that of the control (no T09). To extend the studies in vivo, we treated atherosclerotic apoE−/ − mice (n=9/group) with the LXR agonist (50 mg/kg/day) or saline for 2 weeks. Using laser capture microdissection, we isolated lesional macrophages and found expression of downstream targets of LXR such as ABCA1, ABCG1, and ABCG4 to be up-regulated by 3.7, 4.4, and 3.1X, respectively, as assessed by quantitative real-time PCR. Interestingly, CCR7 expression was found to be increased by 3.7X. This result was confirmed at the protein level using immunohistochemistry, which showed that CCR7 expression was increased in foam cells from the LXR-agonist treated but not the saline-treated group. Morphometric analyses revealed that foam cell content and lesion area decreased by 21% and 24%, respectively. The dependence of these relatively rapid (2 wks) effects on CCR7 was shown by treating apoE−/ − CCR7−/ − atherosclerotic mice (n=8) with T09. After 2 wks, foam cell content only decreased by approximately 9%. In conclusion, CCR7 is a required factor for atherosclerosis regression in a mouse model and LXR regulates its expression in vitro and in vivo.
Immunogenicity of a lambda phage-based anti-cancer vaccine targeting HAAH
Authors: Steven Fuller, Solomon Stewart, Michael Lebowitz, Kanam Malhotra, Mark Semenuk, Biswajit Biswas, Hossein Ghanbari
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts We have designed, developed and produced a lambda-phage based anti-cancer vaccine (nano-particle) targeting human aspartyl (asparaginyl) β-hydroxylase (HAAH). This follows accumulated evidence that HAAH meets requirements of a good target for anti-cancer immunotherapy. The
Severe metabolic alkalosis
Authors: R. W Penman
Journal: BMJ (1981)

Twenty patients out of 38 (52 60' ) who had undergone haemodialysis for one to 80 months (mean 28 1 months) were found to have eosinophilia (eosinophils > 400/mm3) in a random examination (December 1980) in the first unit, while 16 out of 31 patients (51 6%) whose dialysis had lasted from three to 68 months (mean 29-7 months) had eosinophilia in the second unit.Thirty patients from the latter unit who had received dialysis for 20-72 months, who had eosinophil counts at least once a month, were included in this study also.Sixteen out of 30 of these (5333%) never developed eosinophilia during the observation period, six (20%) developed constant eosino- philia, and eight (26 7%) developed transient eosinophilia.This study also shows that during the first two years there is a progressive increase in the mean eosinophil count of the patients, which remains almost constant during the following years (figure).No correlation was found with 4.00 300-Mean eosinophil count/mm¾3 SE 200 - n= 18 100 Before 1 2 3 4 dialysis Years on dialysisEosinophil counts in patients undergoing dialysis.
Seat belts and risk compensation.
Authors: M Mackay
Journal: BMJ (1985)

The author applies the theory that the introduction of any safety measure results in changes in the behaviour of road users which may negate the supposed benefits of the measure and cites examples already established. Research shows that drivers wearing seat belts in fact take fewer risks than those who do not, but the numbers of casualties since the seat belt law tend to support the risk compensation hypothesis. It is suggested however that there has been a 7% increase in road traffic, particularly cyclists under 15 and that the increase in casualties can be accounted for within the normal seasonal and annual fluctuations. It is concluded that risk compensation does not apply, the reduction in death and injury to front seat passengers fully justify the seat belt legislation and that it should be extended to rearseat occupants. It is also suggested that improvements could be made to restraint systems and car interiors to prevent the type of injuries now most frequent. (TRRL)
Interposed abdominal compression-cardiopulmonary resuscitation and resuscitation outcome during asystole and electromechanical dissociation.
Authors: J B Sack, M B Kesselbrenner, A Jarrad
Journal: Circulation (1992)

BACKGROUND Coronary perfusion pressure has been shown to be a significant determinant of return of spontaneous circulation from cardiac arrest during asystole and electromechanical dissociation. The addition of interposed abdominal compression to otherwise standard cardiopulmonary resuscitation (CPR) increases coronary perfusion pressure in animal and human models. METHODS AND RESULTS Accordingly, we conducted a randomized prospective study of 143 consecutive patients experiencing cardiac arrest in a large university-affiliated teaching hospital in whom the initial arrest rhythm was asystole or electromechanical dissociation. Patients were randomized to receive either interposed abdominal compression-CPR or standard CPR. The two end points studied were return of spontaneous circulation and 24-hour survival. In addition, we studied the complications associated with interposed abdominal compression-CPR. Sixty-nine men and 74 women with a mean age of 64 years (range, 19-97 years) were studied. The overall rate of return of spontaneous circulation was 38%. Return of spontaneous circulation was significantly greater in the group receiving interposed abdominal compression-CPR compared with the group receiving standard CPR (49% versus 28%, p = 0.01). At 24 hours, there was a significantly greater number of patients alive in the experimental group than in the control group (33% versus 13%, p = 0.009). We found no complication directly related to the procedure of interposed abdominal compression in a small subset of patients who died and underwent necropsy. CONCLUSIONS We conclude that the addition of interposed abdominal compression may be a useful adjunct to otherwise standard CPR that can improve resuscitation outcome of patients experiencing in-hospital cardiac arrest from asystole and electromechanical dissociation.
Poly(ADP-Ribose) polymerase (PARP) inhibitors: Exploiting a synthetic lethal strategy in the clinic
Authors: Timothy A. Yap, Shahneen K. Sandhu, Craig P. Carden, Johann S. de Bono
Journal: CA A Cancer Journal for Clinicians (2011)

Poly(ADP-ribose) polymerase (PARP) is an attractive antitumor target because of its vital role in DNA repair. The homologous recombination (HR) DNA repair pathway is critical for the repair of DNA double-strand breaks and HR deficiency leads to a dependency on error-prone DNA repair mechanisms, with consequent genomic instability and oncogenesis. Tumor-specific HR defects may be exploited through a synthetic lethal approach for the application of anticancer therapeutics, including PARP inhibitors. This theory proposes that targeting genetically defective tumor cells with a specific molecular therapy that inhibits its synthetic lethal gene partner should result in selective tumor cell killing. The demonstration of single-agent antitumor activity and the wide therapeutic index of PARP inhibitors in BRCA1 and BRCA2 mutation carriers with advanced cancers provide strong evidence for the clinical application of this approach. Emerging data also indicate that PARP inhibitors may be effective in sporadic cancers bearing HR defects, supporting a substantially wider role for PARP inhibitors. Drugs targeting this enzyme are now in pivotal clinical trials in patients with sporadic cancers. In this article, the evidence supporting this antitumor synthetic lethal strategy with PARP inhibitors is reviewed, evolving resistance mechanisms and potential molecular predictive biomarker assays are discussed, and the future development of these agents is envisioned. CA Cancer J Clin 2011. © 2011 American Cancer Society.
Women's understanding of abnormal cervical smear test results: a qualitative interview study
Authors: A. M Kavanagh, D. H Broom
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To describe how women interpret their experiences of diagnosis and treatment of a cervical abnormality and how healthcare services for such women can be improved. <b>Design:</b> Qualitative study using detailed individual interviews. <b>Setting:</b> Australian gynaecology clinics. <b>Subjects:</b> 29 Women who had a cervical cytological abnormality and who attended a gynaecologist. <b>Main outcome measures:</b> Women9s views on their diagnosis and their information needs. <b>Results:</b> Most women wanted to participate in decisions about their care but found it difficult to get the information they required from doctors because they were confused by what their doctors told them and felt unable to ask questions in the consultation. Medical terms such as wart virus and precancer were difficult to understand. Not being able to see their cervix also made it hard for women to understand what their abnormality meant and what treatment entailed. Most women tried to make sense of their abnormality in the context of their everyday lives. For some women their gynaecological care was not consistent with the way they understood their abnormality. <b>Conclusions:</b> The inherent power structure of medical practice combined with time pressures often make it difficult for doctors to give the detailed information and reassurance patients need when a diagnosis is distressing or when investigation and treatment are strange and upsetting. <h3>Key messages</h3> Women who have abnormalities detected on cervical smears are confused, afraid, and find it difficult to get the information they require In this study women often assumed that they had cancer because they did not know that smear tests detected precancerous lesions Women needed information about the seriousness of their abnormality, the rationale for treatment, and the precautions recommended after treatment Because the abnormality involved the cervix many women felt their femininity was undermined Women used explanations such as stress, the pill, or sexual activity to make sense of their condition and through these explanations identified things they could do to reduce their risk of cervical cancer
Cross-National Study of Diagnosis of the Mental Disorders: Methodology and Planning
Authors: JOSEPH ZUBIN
Journal: American Journal of Psychiatry (1969)

The author describes the instruments that have been developed to provide an objective basis for making reliable diagnoses in the cross-national study. Armed with these tools, the investigators designed an experimental approach to examining patients admitted to a London and a New York mental hospital. The author also outlines the next steps in the study.
Diagnosis of Meckel Diverticulum
Authors: John G. Matt
Journal: JAMA (1976)

To the Editor.—  Dr Max Cooper (235: 1471, 1976) is to be complimented for using a sodium pertechnetate Tc 99m scan to correctly diagnose a case of bleeding Meckel diverticulum preoperatively.  Some years ago I reviewed all of the cases of bleeding Meckel diverticulum that had been reported up to that time ( American Journal of Surgery 47:612, 1940). This study indicated that the triad of (1) a young male patient, (2) recurrent episodes of melena, and (3) mild abdominal discomfort, was just about pathognomonic for bleeding Meckel diverticulum. This observation has been confirmed repeatedly by various authors since that time.  I am convinced that intricate, time-consuming, and expensive diagnostic studies are hardly justifiable in the instance of a 22-month old boy with a history of three episodes of painless melena in his lifetime and normal physical findings. Small bowel barium examinations rarely demonstrate a Meckel diverticulum. Dr Cooper, himself, reports
Abstract 4264: NFκB activation in mesenchymal stromal cells induced by leukemia-stroma interaction plays a central role in stroma-mediated chemo-resistance of leukemic cells
Authors: Rodrigo O. Jacamo, Ye Chen, Zhiqiang Wang, Wencai Ma, Min Zhang, Batulla L. Venkata, Wendy D. Schober, Richard E. Davis, Marina Konopleva, Michael Andreeff
Journal: Cancer Research (2012)

Abstract Within the bone marrow (BM) microenvironment, BM mesenchymal stromal cells (BM-MSC) produce cytokines and chemokines and initiate cellular adhesion-mediated signals that tightly regulate normal and malignant hematopoietic cell development. This rich environment serves as a sanctuary for malignant hematopoietic cells, offering protection from chemotherapeutic agents and promoting residual disease with greater potential for developing acquired drug resistance. In this study we utilized gene expression profiling (GEP) as a genome-wide exploratory approach to characterize changes caused by the interaction between leukemic cells and BM-MSC, and how these changes can contribute to the observed microenvironment-mediated chemoresistance. Co-culture of REH, a pre-B-ALL cell line, with normal-donor BM-MSCs for 48 hours upregulated a variety of genes encoding cytokines and chemokines in BM-MSCs such as CXCR6, CCL5, CCL2, IL32, IL34, IL8, IL6, CXCL12, and the VLA4 ligand VCAM-1. These microarray-based GEP findings were confirmed by qRT-PCR. Gene Set Enrichment Analysis (GSEA) implicated activation of NFκB in BM-MSCs as a potential cause of these changes. Similar upregulation of NFκB target genes was found in MSC co-cultured with the AML cell line OCI-AML3, suggesting that NFκB activation is a common consequence of leukemia-stroma interation. Given known paracrine functions of NFκB-regulated target genes such as IL-8, we hypothesized that stromal NFκB activation contributes to stroma-mediated chemo-resistance of leukemic cells. Stable transduction of BM-MSC to overexpress a super-repressor form of IαBβ (IαBβ-SR), to block canonical-pathway NFκB activation in the stromal compartment, significantly reduced the stroma-mediated chemo-resistance to Vincristine (VCR) of REH cells. NFκB inhibition using a specific IKKα inhibitor (MLN120B), affecting both BM-MSC and tumor cells, highly increased the apoptotic effects in leukemia-stroma co-cultures of VCR in REH cells and NALM6, another pre-B-ALL cell line. Similar results were obtained with CDDO-Me, another NFκB inhibitor. Altogether these results indicate that the interaction of leukemic cells with BM stromal cells activates NFκB in the stromal compartment, with subsequent transcriptional upregulation of a number of cytokines and chemokines ultimately favoring the survival of leukemic cells. We propose that targeting NFκB may ameliorate stroma-mediated chemo-resistance and help in eliminating bone-marrow resident leukemic cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4264. doi:1538-7445.AM2012-4264
Current status of studies concerned with evaluation of toxic effects of chemicals on the testes
Authors: Emil Steinberger
Journal: Environmental Health Perspectives (1981)

A brief review of the history of the subject is provided. An attempt is made to define the current status of the knowledge and the reasons why our knowledge in this area of science is poor. The information gained from studies employing lower species is contrasted with information on the human male. The most commonly utilized techniques for evaluating the effects of toxic agents on the male reproductive system is briefly summarized. The growth of knowledge in physiology, biochemistry, and hormonal control of testicular function during the past ten to fifteen years is discussed; and, the specific most pertinant advances are noted. The difficulties in utilizing the human subject for toxicologic studies are pointed out and the reasons why the knowledge of the effect of toxic agents on the human testes are meager are discussed. The methodology utilized for the study of the functional integrity of the human testes and the specific parameters widely utilized for this purpose are discussed and criticized. The fact that it is extremely difficult to evaluate changes in the testicular function of men are emphasized and the extremely wide variability is pointed out. Furthermore, it is demonstrated that at this moment, we are lacking some of the most fundamental information concerning the normal function of the human testes; and, that there is a poor understanding of parameters of “normalcy”. The three parameters used most commonly to define normalcy of human testes, namely, testicular histology, sperm output, and hormonal levels are discussed and the difficulties and pitfalls of these measurements are pointed out.
Another Look at the Patient
Authors: David D. Rutstein
Journal: New England Journal of Medicine (1962)

IN devoting this Class Day Address to some of the A problems that you face in your choice of a career in medicine, I wish to focus on a future for the physician consistent with the dignity in which he has long been held. In the book of Ecclesiasticus in the Apocrypha, Jesus the son of Sirach wrote, "Honor the physician. . . for thou hast need of him." At a time when the physician seems to have turned from the priesthood to the market place, yours will be the difficult task of reversing the present trend and increasing public . . .
The regulatory mechanism by extracellular nucleotides in hepatic microcirculation
Authors: S TAKEMURA
Journal: Hepatology (1995)

ObjectiveIn vivo, chondrocytes are surrounded by an extracellular matrix, preventing direct cell-to-cell contact. Consequently, intercellular communication through gap junctions is unlikely. However, signaling at a distance is possible through extracellular messengers such as nitric oxide (NO) and nucleotides and nucleosides, adenosine triphosphate (ATP), uridine triphosphate (UTP), or adenosine diphosphate (ADP). We hypothesized that chondrons, chondrocytes surrounded by their native pericellular matrix, increase their intracellular calcium concentration ([Ca2+]ic) in response to ATP and other signaling molecules and that the source of Ca2+is from intracellular stores. The objectives of this study were to determine if chondrons in a 3-D gel respond to ATP by increasing [Ca2+]icthrough a purinoceptor mechanism and to test whether chondrons in whole tissue samples would respond to ATP in a similar fashion.Design Human chondrons, cultured in a three-dimensional agarose gel or in whole cartilage loaded with Fura-2AM, a calcium sensitive dye, were stimulated with 1, 5 and 10 μM ATP. A ratio-imaging fluorescence technique was used to quantitate the [Ca2+]ic.Results ATP-stimulated chondrons increased their [Ca2+]icfrom a basal level of 60 nM to over 1000 nM. Chondrons incubated in calcium-free medium also increased their [Ca2+]icin response to ATP, indicating the source of Ca2+was not extracellular. ATP-induced calcium signaling was inhibited in chondrons pre-treated with suramin, a generic purinoceptor blocker. In addition, UTP and adenosine 5′-O-(3-thiotriphosphate) (ATPγs) induced a calcium response, but 2-methylthio-ATP (2-MeSATP), ADP, and adenosine did not induce a significant increase in [Ca2+]ic, substantiating that the P2Y2purinoceptor was dominant. Chondrons in whole cartilage increased [Ca2+]icin response to ATP.Conclusions We conclude that chondrons in 3-D culture respond to ATP by increasing [Ca2+]icvia P2Y2receptor activation. Thus, ATP can pass through the agarose gel and the pericellular matrix, bind purinoceptors and increase intracellular Ca2+in a signaling response.
Thyroid Carcinoma After Exposure to Atomic Radiation
Authors: LAWRENCE N. PARKER
Journal: Annals of Internal Medicine (1974)

A survey of histologically verified thyroid carcinoma in the Atomic Bomb Casualty Commission—Japanese National Institute of Health (ABCC-JNIH) Adult Health Study, from July 1958 through October 1971 was made, using as sources of tumor information results of periodic clinical examinations, autopsy diagnoses, surgical pathology reports, tumor registry listings, and death certificate diagnoses. Thyroid carcinoma was commoner in women and significantly more prevalent in persons exposed to 50 or more rads of atomic radiation 13 to 26 years previously. Carcinoma of the thyroid diagnosed during life was commoner in persons who were less than 20 years old when exposed in 1945; however, a radiosensitive period only in childhood, found in previous studies, was not shown in this study, since an increased risk was found even among persons who were 50 years old at the time of radiation exposure.
Another form of familial intrahepatic cholestasis, another new genek
Authors: Frederick J. Suchy
Journal: Hepatology (1999)

The progressive familial intrahepatic cholestases (PFIC) are a group of inherited disorders with severe cholestatic liver disease from early infancy.A subgroup characterized by normal serum cholesterol and ␥-glutamyltranspeptidase (␥-GT) levels is genetically heterogeneous with loci on chromosomes 2q (PFIC2) and 18q.The phenotype of the PFIC2-linked group is consistent with defective bile acid transport at the hepatocyte canalicular membrane.The PFIC2 gene has now been identified by mutations in a positional candidate, BSEP, which encodes a liver-specific ATP-binding cassette (ABC) transporter, sister of pglycoprotein (SPGP).The product of the orthologous rat gene has been shown to be an effective bile acid transporter in vitro.These data provide evidence that SPGP is the human bile salt export pump (BSEP). COMMENTS
Repetitive Maternal-Fetal Transmission of Fatal Hepatitis B
Authors: Karim A. Fawaz, George F. Grady, Marshall M. Kaplan, Sydney S. Gellis
Journal: New England Journal of Medicine (1975)

FATAL hepatitis was observed in two three-month-old infants born successively to an asymptomatic carrier of hepatitis B surface antigen (HBs Ag). We attempted to place these unusual cases in perspective by reviewing the current literature bearing on the need for screening pregnant women for HBs Ag, for counseling those found positive, and for attempting immunoprophylaxis of hepatitis B among their offspring.Case ReportsIndex CaseAfter an uncomplicated gestation, full-term delivery, and three months of normal growth and development, a male infant was hospitalized with vomiting, lethargy, and jaundice of three days' duration. He was alert but irritable, . . .