tbuckley/cabot-search huggingface dataset:
Abstract 1457: Valproic acid enhances radiation therapy by protecting normal hippocampal neurons and sensitizing malignant glioblastoma cells
Authors: Kyle Sweeney, Sandeep Bhave, Rong Hu, Jerry Fong, Dennis Hallahan, Dinesh Kumar Thotala
Journal: Cancer Research (2012)

Abstract Neurocognitive deficits are devastating sequelae that follow cranial irradiation in patients with medulloblastoma and leukemia. Valproic acid (VPA) has been used effectively as a neuroprotector in various neurological insults. In the present study we demonstrate that VPA could be used to protect hippocampal neurons from the damaging effects of radiation. The effect of VPA pretreatment on cell death was examined using clonogenic survival assays. Mouse hippocampal neurons, HT-22 were treated with 0.6 mM VPA for 7 days prior to irradiation. A significant increase in survival was seen in HT-22 cells treated with VPA compared to cells treated with radiation alone. In contrast, VPA treatment decreased the survival of irradiated cancer cells, D54 and GL-261 compared to radiation alone. To elucidate the mechanism of this selective increased survival in normal hippocampal cells we monitored for program cell death by Annexin V-FITC or DAPI staining. Irradiated HT-22 cells which were pretreated with VPA demonstrated 2 fold decrease in apoptosis than irradiated cells. Similar results were obtained using irradiated mice. Seven-days old C57BL6J pups were either irradiated with the single dose of 7 Gy or treated with VPA (200mg/Kg) followed by 7Gy irradiation. VPA pretreatment protected hippocampal neurons from radiation-induced apoptosis as demonstrated by counting the pyknotic nuclei in the subgranular zone of the hippocampal region. Western immunoblotting of HT-22 cells revealed that VPA not only inhibited HDAC, but also inhibited glycogen synthase kinase-3β (GSK-3β), an enzyme required for apoptosis. A heterotopic glioma model of GL-261 was used to evaluate the tumor growth delay following treatment with VPA (200 mM) and radiation (five fractions of 2Gy). VPA alone delayed the tumor growth; however VPA in combination with radiation significantly delayed tumor growth. In conclusion, VPA protected hippocampal neurons from radiation-induced damage in vitro and in vivo. This protection is specific to hippocampal neuronal cells and not to cancer cells. The molecular mechanism could involve enzymatic inhibition of both HDAC and GSK-3β. VPA could be used as a novel therapy for the prevention of neurocognitive deficits resulting from cranial irradiation. 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 1457. doi:1538-7445.AM2012-1457
Expression of Human Herpesvirus 8-Encoded Cyclin D in Kaposi's Sarcoma Spindle Cells
Authors: M. A. Davis, S. R. Opalenik, P. J. Browning, M. Sturzl, C. Blasig, A. Schreier, H.-G. Guo, M. Reitz
Journal: JNCI Journal of the National Cancer Institute (1997)

Human herpesvirus 8 (HHV-8) DNA sequences have been detected in Kaposi's sarcoma, in primary effusion lymphoma (an unusual high-grade non-Hodgkin's lymphoma seen primarily in patients with acquired immunodeficiency syndrome [AIDS]), and in Castleman's disease (a rare lymphoproliferative disorder); however, proof that HHV-8 is involved in the pathogenesis of these diseases remains to be established. HHV-8 contains a gene, i.e., v-cyclin D, that is a homologue of the cellular cyclin D2 gene, which encodes a protein that promotes passage through G1 phase of the cell cycle. Previous studies have identified v-cyclin D messenger RNA (mRNA) in biopsy specimens of Kaposi's sarcoma. In this study, we isolated a full-length v-cyclin D complementary DNA and characterized the pattern of v-cyclin D mRNA expression in Kaposi's sarcoma.Standard methods were used to construct and to screen HHV-8 genomic and complementary DNA libraries. Reverse transcription-polymerase chain reaction (RT-PCR) methods and in situ hybridization with RNA probes were used to examine v-cyclin D mRNA expression.RT-PCR demonstrated the presence of v-cyclin D mRNA in biopsy specimens of AIDS-related Kaposi's sarcoma, in early-passage spindle cells from classical (i.e., not AIDS-related) Kaposi's sarcoma, and in spindle cells isolated from the peripheral blood of patients with AIDS-related Kaposi's sarcoma. In situ hybridization indicated that mRNAs for v-cyclin D and kaposin, an HHV-8 latency-associated gene, were present in approximately 1% of the spindle cells in early patch lesions and approximately 60% of the spindle cells in late nodular lesions of Kaposi's sarcoma.Spindle cells of Kaposi's sarcoma, which have been regarded as the tumor cells of this cancer, contain v-cyclin D mRNA. Expression of v-cyclin D protein may be involved in the pathogenesis of Kaposi's sarcoma by promoting cell proliferation.
Early-Morning Hyperglycemia in Diabetic Individuals Treated with Continuous Subcutaneous Insulin Infusion
Authors: Mitchell E Geffner, Harrison J Frank, Solomon A Kaplan, Barbara M Lippe, Seymour R Levin
Journal: Diabetes Care (1983)

Significant early-morning hyperglycemia was observed in insulin-dependent diabetic individuals who were otherwise well controlled while receiving a continuous subcutaneous insulin infusion (CSII) at standard doses. We measured the levels of the five key counterregulatory hormones (CRH) throughout the night for a total of 10 patient-nights in four such patients. No abnormalities in the patterns of glucagon, cortisol, growth hormone, epinephrine, or norepinephrine secretion were observed. Stepping up the daytime basal infusionrate in six affected patients before bedtime by 37.0 ± 7.5% and maintaining the increased infusion until breakfast significantly blunted this early-morning hyperglycemia without causing significant early nighttime hypoglycemia. Plasma glucose concentrations before breakfast averaged 106.8 ± 13.0 mg/dl after increase of the overnight basal infusion rate as compared with 269.8 ± 39.1 mg/dl while receiving a single basal rate over 24 h (P &amp;lt; 0.02). Thus, the “dawn phenomenon” may occur in patients receiving CSII by an unmodified algorithm and may be obviated by a carefully determined step-up in nocturnal basal infusion rate. The mechanism responsible for this phenomenon of increased early-morning insulin need remains to be elucidated.
Diphenhydramine Abuse and Withdrawal-Reply
Authors: Marc D. Feldman
Journal: JAMA (1986)

<h3>In Reply.—</h3> We are delighted to comment on Dr Glickman's response to our report. In view of the features common to withdrawal from many sedating drugs, we find it difficult to ascribe our patient's irritability and insomnia specifically to rebound from the anticholinergic and not the sedative effects of diphenhydramine. Similarly, akathisia or a related syndrome could not be established in this case, so Dr Glickman's extrapolation from antidepressant and neuroleptic withdrawal to diphenhydramine withdrawal must remain speculative, although intriguing. If akathisia had in fact occurred, however, the patient's thiothixene use would be a more likely cause. It is important to note as well that rituals may indeed be of great magnitude, and our patient's bedtime behavior was characteristically repetitive, stereotyped, compulsive, and calming. Dr Glickman's final suggestions certainly merit avid consideration. The point of our publishing this case was not to offer a recipe for diphenhydramine tapering but to
Isometric exercise in patients with chronic advanced heart failure: hemodynamic and neurohumoral evaluation.
Authors: U Elkayam, A Roth, L Weber, W Hsueh, M Nanna, L Freidenberger, P A Chandraratna, S H Rahimtoola
Journal: Circulation (1985)

We evaluated the hemodynamic effects of isometric exercise in 53 patients with congestive heart failure (CHF) and compared them with those found in 10 normal subjects. In both groups, isometric exercise increased heart rate and blood pressure. Systemic resistance increased in patients with CHF (1862 +/- 520 vs 2126 +/- 642 dyne-sec-cm-5; p less than .001) but not in normal subjects (1359 +/- 268 vs 1380 +/- 252 dyne-sec-cm-5). Cardiac index and stroke volume index increased mildly but not significantly in the normal subjects (2.8 +/- 0.5 vs 3.1 +/- 0.7 liters/min/m2 and 46 +/- 8 vs 47 +/- 7 ml/m2) and showed a significant fall in the patients with CHF (2.1 +/- 0.6 to 1.9 +/- 0.6 liters/min/m2, p less than .01 and 23 +/- 7 vs 20 +/- 7 ml/m2, p less than .01). Mean pulmonary arterial wedge pressure increased in patients with CHF from 26 +/- 7 to 30 +/- 8 mm Hg (p less than .001). Although no significant change was found in mean value for stroke work index (21 +/- 9 vs 20 +/- 9 g-m/m2), the individual changes were variable, with marked decrease (greater than 15%) in 17 of the patients. This hemodynamic deterioration could not be predicted from resting hemodynamics, left ventricular ejection fraction, or functional classification. Isometric exercise resulted in no significant change in circulatory catecholamine levels or plasma renin concentration in our 10 normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
ON THE RELATION OF NECROSIS AND INFLAMMATION TO DENATURATION OF PROTEINS
Authors: Eugene L. Opie
Journal: The Journal of Experimental Medicine (1962)

Necrosis of the skin was produced by the injection of measured quantities of electrolytes and of amino compounds into the dermis, and the relative ability of these substances to produce it was determined. Inflammation characterized by edema and accumulation of leucocytes accompanied necrosis. The ability of electrolytes to produce necrosis was found to increase with the valence of their basic ion, and in this respect was in accord with their ability to denature proteins. The quantity of different electrolytes needed to produce necrosis varied in the same order as the molar concentration of these electrolytes, that is isotonic with liver or kidney cells. Necrosis caused by amino compounds occurred with similar relation to the isotonicity of liver cells. In this as in other relations the cells acted as osmometers. The foregoing relations indicate that denaturation of proteins, necrosis of living tissue, and osmotic activity of liver or kidney cells are determined by molecular weight, valence, and ion-dissociation of electrolytes, that is, by the factors that determine the colligative properties of electrolytes. Agents such as turpentine, mustard, or croton oil and some halogen substitution compounds of methyl that are insoluble in water and soluble in lipoids have produced skin necrosis and inflammation.
Phenylbutazone liver injury: A clinical-pathologic survey of 23 cases and review of the literature
Authors: Stanley B. Benjamin, Kamal G. Ishak, Hyman J. Zimmerman, Amos Grushka
Journal: Hepatology (1981)

Phenylbutazone has been reported to produce several forms of hepatic injury. A clinical and histologic review of 23 well-substantiated cases in conjunction with review of 43 case reports in the literature was undertaken. Utilizing the histologic features and available clinical data, the injury was classified as moderate-marked hepatocellular injury, minor hepatocellular injury, and other injury. No sexual differences were noted. Most patients had used the drug for less than 6 weeks. Features of hypersensitivity were common. Granulomas on liver biopsy were seen mainly in association with clinical evidence of hypersensitivity nd with minor hepatocellular liver injury. The majority of deaths occurred in cases with significant hepatocellular injury or systemic vasculitis. Analysis of available data suggests that, although hypersensitivity appears to contribute to phenylbutazone-associated hepatic injury, the drug also appears to have intrinsic hepatotoxic potential. Speculation is offered regarding the relative role of these two mechanisms in the several forms of hepatic injury induced by phenylbutazone.
Prostaglandin endoperoxide synthetase isoenzymes: the clinical relevance of selective inhibition.
Authors: J.C Frölich
Journal: Annals of the Rheumatic Diseases (1995)

Prostaglandin endoperoxide synthetase isoenzymes: the clinical relevance of selective inhibition Prostaglandins are mediators of inflammation, synthesised from arachidonic acid by cyclo-oxygenase.Inhibition of prostaglandin biosynthesis by blocking cyclo-oxygenase underlies the analgesic, anti-inflammatory, and antipyretic actions of the non-steroidal anti-inflammatory drugs (NSAIDs).The side effects of these drugs, including damage to the gastric wall and kidney, and inhibition of platelet aggregation, are also believed to be caused by inhibition of cyclo-oxygenase.'Most interestingly, the action of steroids has also been explained on the basis of inhibition of prostaglandin synthesis.Most of the experi- ments supporting these findings were obtained in in vitro or in animal studies, but in normal volunteers acetylsalicylic acid, indomethacin, diclofenac, ibuprofen, and other NSAIDs have been shown to cause inhibition of prosta- glandin synthesis, platelet thromboxane production, and renal sodium excretion.However, the NSAIDs are not as uniform a group of drugs as these statements may suggest.For example, paracetamol is a weak anti-inflammatory drug only, and does not inhibit platelet aggregation.The suggestion was made, therefore, that paracetamol might act predominantly on a cyclo-oxygenase in the brain to produce analgesia-in effect thus predicting the existence of differ- ent forms of cyclo-oxygenase.2A study of salicylic acid in man revealed that it had no antiaggregatory effect and, in contrast to acetylsalicylic acid, did not cause inhibition of prostaglandin synthesis in normal volunteers, in spite of equal anti-inflammatory activity.3Furthermore, gluco- corticoids, while causing inhibition of prostaglandin synthesis in in vitro studies, were ineffective in vivo.4I The authors suggested that a highly stimulated rate of prosta- glandin production was in effect in the in vitro experiments, in contrast to a basal rate of production in vivo, and that this could be responsible for the different responses to the drugs.4The discovery of two different cyclo-oxygenases, now known as COX I and COX II, has enabled the resolution of some of these discrepancies, and ushered in a new generation of NSAIDs.6 7 COX I is the constitutive enzyme serving our basic physiological functions mediated by prostaglandins.These include regulation of peripheral vascular resistance, renal blood flow, renal sodium excretion, and renin.Their inhibition can result in renal failure, sodium retention, and loss of control of hypertension.COX I also is present in blood platelets and is important for aggregation mediated by thromboxane A2.Products of COX I in the on July 23,
Gender and Stress
Authors: Alexandra Symonds
Journal: JAMA (1989)

<i>Gender and Stress</i>is an impressive, in-depth study of a subject of concern to all clinicians and students of human behavior. What accounts for the gender differences we note in certain medical and psychological conditions? Why do women live longer than men? Why do women have less coronary heart disease and hypertension, especially in the premenopausal years, ie, earlier than men? Women seek medical help more often than men. Are they sick more often, or do they seek help earlier in the course of the disease? Why is the incidence of depression in women two to three times that of men? Most of us have our own personal explanations for these gender differences, but the experts in the field do not find things so clear-cut. It has been presumed that women's health is protected because they have not been in the workplace. If this is true, then as more women
CA19-9 and Pancreatic Cancer
Authors: Patrick M. Dunn, Mark McKinstry
Journal: Annals of Internal Medicine (1989)

Letters and Corrections15 August 1989CA19-9 and Pancreatic CancerPatrick M. Dunn, MD, Mark McKinstry, MDPatrick M. Dunn, MDSearch for more papers by this author, Mark McKinstry, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-111-4-343_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: Pleskow and colleagues (1) suggest that the serologic marker, CA 19-9, "can be used in combination with a single imaging modality to achieve high diagnostic accuracy in patients with suspected pancreatic cancer." We have two concerns about the clinical utility of CA 19-9: First, we do not believe it will be useful in most patients being evaluated for pancreatic cancer; second, the value chosen by the authors to distinguish normal from abnormal is not optimal.Patients suspected of having a pancreatic malignancy require the most definitive test possible, given the significant implications of the diagnosis. A marker...References1. PleskowBergerGyvesAllenMcLeanPodolsky DHJEAD. Evaluation of a serologic marker, CA 19-9, in the diagnosis of pancreatic cancer. Ann Intern Med. 1989;110:704-9. LinkGoogle Scholar2. Metz C. Basic principles of ROC analysis. Seminars in Nuclear Medicine. 1978;8:283-98. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byComprehensive analysis of clinical prognosis and CLIC1 immune invasion in lung adenocarcinomaMarked elevation of CA19-9 in a patient with idiopathic pulmonary fibrosis: CA19-9 as a bad prognostic factorCA 19–9, GICA (Gastrointestinal Cancer Antigen)Diagnosing cancer of the pancreas. 15 August 1989Volume 111, Issue 4Page: 343-343KeywordsPancreatic cancer ePublished: 1 December 2008 Issue Published: 15 August 1989 PDF downloadLoading ...
Mentalizing Language Development in a Longitudinal Attachment Sample: Implications for Alexithymia
Authors: Erwin Lemche, Gisela Klann-Delius, Rainer Koch, Peter Joraschky
Journal: Psychotherapy and Psychosomatics (2004)

The construct of alexithymia implies a deficit in symbolization for emotional, somatic, and mental states. However, the etiologic factors for alexithymia have not yet been fully elucidated. The present study investigated the use of mentalizing language, i.e. the utterance of internal states, from a developmental perspective according to attachment organization and disorganization.A longitudinal design across 4 time points was applied to a volunteer sample of 42 children. At 12 months, children were tested with the strange situation procedure, the standard measure of attachment at the optimal age, and attachment classifications were taken of videotapes. At ages 17, 23, 30 and 36 months, mother and child were observed in simplified separation episodes of 30 min duration. Transcripts of the sessions were subject to coding of internal state words.During the investigated span, securely attached children rapidly acquired emotion, physiology, cognition and emotion-regulatory language, whereas insecurely attached and disorganized children either completely lacked internal state language or displayed a considerable time lag in the use of emotion and cognition vocabulary.The results raise the possibility that alexithymia might be a consequence of deficits in the development of internal state language in the context of insecure or disorganized childhood attachment relationships.
Dual Focus in Brief Psychodynamic Psychotherapy
Authors: Stephen Armstrong
Journal: Psychotherapy and Psychosomatics (1980)

The therapist needs to choose well the focus of treatment in brief psychodynamic psychotherapy, lest the therapy become fragmented. The therapeutic focus is crucial to the treatment of very impaired patients, in whom many experiences of themselves or others are compartmentalized or split off. Without a focus as a therapeutic tool to reintegrate these experiences, the patient becomes confused by interpretations directed at multiple, segregated parts of him or herself. When the therapist has not established a treatment focus, the therapist also becomes confused by the patient's multiple experiences of self and others. A case example illustrates the therapy of a patient who required dual foci arranged sequentially, in which the therapist treated three aspects of the patient's self-image as a primary focus, and the patient's grief over two stillborn children as a second focus. The patient could not grieve until the primary focus helped repair the breech in the patient's self-image.
Hippocrates on Psychotherapy by the General Practitioner
Authors: Stanley L. Block
Journal: New England Journal of Medicine (1957)

IN the past twenty-five hundred years the number of reviews, commentaries, critiques and translations of the Hippocratic writings is astounding. The effect of these writings in freeing medicine from magic and mysticism and their emphasis on natural causation of disease and on the importance of the observational method have been particularly emphasized. Attention has been called to the humoral theory and to the theory of prognosis, to the case histories, to medical practice and to surgical practice, as well as to medical ethics and certain aspects of psychiatric practice. Unfortunately, little emphasis has been placed on some of the Hippocratic . . .
Abstract 2055: p21CIP1 mediates reciprocal switching between invasion and proliferation during metastasis
Authors: Rachel Hazan
Journal: Cancer Research (2012)

Abstract Cell proliferation and invasion are critical for malignant progression, yet how these processes relate to each other and whether they regulate one another during metastasis is unknown. We show that invasiveness of breast cancer cells is associated with growth arrest due to p21CIP1 upregulation. Knockdown of p21CIP1 increases proliferation and suppresses invasion. Since p21CIP1 acts to inhibit Cyclin E during cell cycle progression, we demonstrated that a constitutively active form of Cyclin E had similar effects to p21CIP1 inhibition resulting in increased proliferation and suppressed invasion. We tested these findings in vivo in the Polyoma middle T mammary tumor model in which p21CIP1 was deleted. p21CIP1 knockout mice exhibited dramatic suppression of metastasis, independent of tumor growth. Metastasis suppression was associated with striking cytoskeletal reorganization leading to a shift from stress fibers to cortical actin, tightening of cell junctions, and cytokeratin upregulation. Thus, P21CIP1 regulates metastasis by mediating dynamic switching between invasion and proliferation. 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 2055. doi:1538-7445.AM2012-2055
Religion and Spirituality in Psychiatry
Authors: Philip E. Veenhuis
Journal: JAMA (2010)

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