tbuckley/cabot-search huggingface dataset:
Neuroanatomical Correlates of Childhood Sexual Abuse: Identifying Biological Substrates for Environmental Effects on Clinical Phenotypes
Authors: Maria A. Oquendo, Jeffrey M. Miller, M. Elizabeth Sublette
Journal: American Journal of Psychiatry (2013)

Sexual abuse during childhood is surprisingly common, with estimates in the general population ranging from 15% to 38% (1).It is associated with significant psychiatric sequelae, including the development of major depression and posttraumatic stress disorder (PTSD).These common consequences of exposure to trauma can emerge in the aftermath of natural disasters as well as those in which humans have a hand (2).Some responses, such as suicidal behavior, are not only life-threatening but have multigenerational repercussions, as individuals who report childhood sexual abuse are at risk not only for suicidal behavior themselves but also for transmitting suicidal behavior and mood disorders to their offspring (3).The timing (4) and severity of childhood sexual abuse are also relevant to its consequences (5).Earlier age at onset of childhood sexual abuse is associated with more intent during suicide attempts (6) as well as greater severity of PTSD (7) and depressive symptoms (8).Similarly, the severity of sexual abuse during development is reportedly related to earlier-onset suicidal behavior (6), greater depression severity (9), and more pronounced symptoms among patients with borderline personality disorder (5).Interestingly, other forms of early life stress, such as childhood emotional abuse and neglect, have been found to be stronger predictors of subsequent depression in adulthood than childhood sexual or physical abuse (10).
Lipoprotein concentrations and carotid atherosclerosis by diabetes status: results from the Insulin Resistance Atherosclerosis Study.
Authors: D C Goff, R B D'Agostino, S M Haffner, M F Saad, L E Wagenknecht
Journal: Diabetes Care (2000)

OBJECTIVE: Lipoprotein concentrations are associated with the development of atherosclerosis in people with and without diabetes. The relative strength of these associations could differ by diabetes status as a result of diabetes-related lipoprotein modifications. RESEARCH DESIGN AND METHODS: The associations between lipoprotein concentrations and internal and common carotid artery intimal-medial thickness (IMT) assessed by B-mode ultrasonography were examined by diabetes status in a cross-sectional analysis among 1,391 participants in the Insulin Resistance Atherosclerosis Study. Participants included 442 individuals with type 2 diabetes, 308 with impaired glucose tolerance, and 641 with normal glucose tolerance. RESULTS: The differences in internal and common carotid IMT between the highest and lowest tertiles of LDL were 58.1 microm (P = 0.054) and 51.0 microm (P &amp;lt; 0.001), respectively. The differences in internal and common carotid IMT between the lowest and highest tertiles of HDL were 56.2 microm (P = 0.07) and 37.8 microm (P = 0.003), respectively Triglycerides and VLDL were not associated with IMT. These associations did not differ significantly because of diabetes status. CONCLUSIONS: These results support the importance of dyslipidemia as a major risk factor for atherosclerosis in people with diabetes. Future research in humans should measure lipoprotein oxidizability, glycation, size, and composition directly in people of differing glucose tolerance status to address the importance of diabetes-related lipoprotein modifications more conclusively.
Regulation of the growth and functions of cloned murine large granular lymphocyte lines by resident macrophages.
Authors: N Minato, T Amagai, J Yodoi, T Diamanstein, S Kano
Journal: The Journal of Experimental Medicine (1985)

Using cloned lines with the morphology of large granular lymphocytes (LGL) from BALB/c mice, we studied the exact requirements for proliferation and their functional characteristics, as well as their regulation. Although these cloned LGL lines were interleukin 2 (IL-2) dependent for growth, experiments using human recombinant IL-2 (rIL-2), known to be active on murine cells, indicated that IL-2 was a necessary but not sufficient factor. Coexistance of normal macrophages in addition to rIL-2 was found to support continuous proliferation of cloned LGL in vitro. This role of macrophages could be replaced by partially purified IL-1 derived from macrophage-conditioned medium. An IL-2 binding assay using 125I-rIL-2 suggested that the role of normal macrophages was to selectively induce and/or maintain high affinity IL-2 receptors (IL-2R) (Kd, 0.2-0.5 nM) without affecting low affinity ones (Kd, 10-30 nM). Functional studies indicated that most of the LGL clones killed various combinations of representative groups of natural killer (NK)-susceptible target cells, including leukemic cells (YAC-1, RL male 1), virus-infected cells (HeLa-measles, HeLa-herpes simplex virus), and normal bone marrow cells (BMC), whereas none of them affected any of NK-resistant target cells, including uninfected HeLa cells. Some of these clones also suppressed in vitro hematopoiesis. Such characteristic cytotoxic spectra, as well as serological phenotypes (Thy-1+, Lyt-1-2-, asialo GM1-positive, T200+, TdT-, Fc receptor-positive) indicated that these LGL clones exactly represent endogenous NK cells, rather than a variety of anomalous killer cells generated in various culture conditions. Although there was significant heterogeneity of cytotoxic spectrum among LGL clones, no clonotypic distribution of specificities was observed. Normal macrophages were found to modulate the functional expression of LGL clones. They augmented the cytotoxic potential of the clones against leukemic and virus-infected targets, but suppressed intrinsic reactivity against normal BMC. Similarly, LGL clones maintained with macrophages showed much less suppressive effect on in vitro hematopoiesis. The present observations on the interaction of cloned LGL and normal macrophages provide a basic explanation for the mechanisms by which the immediate responsiveness to IL-2 of the NK effector system, without exogenous stimulation, and the functional selectivity toward abnormal rather than normal cells, are actively maintained in vivo.
ANIRIDIA IN FIVE GENERATIONS
Authors: Hugh L. Dwyer
Journal: JAMA (1924)

In the course of an examination of school children a few years ago, I encountered a child with hereditary absence of the iris. Tracing her family and relatives, I was able to find nine cases of aniridia and obtain a good family history of fifteen cases in five generations. Some of the children are in school but are seriously handicapped. On a casual inspection of the eye, there seems to be a total absence of the iris, although it is probable that on close examination tags or remnants of this structure remain, as is reported in the majority of cases examined. In this anomaly the influence of heredity is most strikingly seen. The character behaves as a mendelian dominant. The laws of heredity, so well worked out in plants and lower animals, encounter many obstacles in their application to conditions in man. This is due principally to the difficulty in
Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state
Authors: Marc Foretz, Sophie Hébrard, Jocelyne Leclerc, Elham Zarrinpashneh, Maud Soty, Gilles Mithieux, Kei Sakamoto, Fabrizio Andreelli, Benoit Viollet
Journal: Journal of Clinical Investigation (2010)

Metformin is widely used to treat hyperglycemia in individuals with type 2 diabetes. Recently the LKB1/AMP-activated protein kinase (LKB1/AMPK) pathway was proposed to mediate the action of metformin on hepatic gluconeogenesis. However, the molecular mechanism by which this pathway operates had remained elusive. Surprisingly, here we have found that in mice lacking AMPK in the liver, blood glucose levels were comparable to those in wild-type mice, and the hypoglycemic effect of metformin was maintained. Hepatocytes lacking AMPK displayed normal glucose production and gluconeogenic gene expression compared with wild-type hepatocytes. In contrast, gluconeogenesis was upregulated in LKB1-deficient hepatocytes. Metformin decreased expression of the gene encoding the catalytic subunit of glucose-6-phosphatase (G6Pase), while cytosolic phosphoenolpyruvate carboxykinase (Pepck) gene expression was unaffected in wild-type, AMPK-deficient, and LKB1-deficient hepatocytes. Surprisingly, metformin-induced inhibition of glucose production was amplified in both AMPK- and LKB1-deficient compared with wild-type hepatocytes. This inhibition correlated in a dose-dependent manner with a reduction in intracellular ATP content, which is crucial for glucose production. Moreover, metformin-induced inhibition of glucose production was preserved under forced expression of gluconeogenic genes through PPARgamma coactivator 1alpha (PGC-1alpha) overexpression, indicating that metformin suppresses gluconeogenesis via a transcription-independent process. In conclusion, we demonstrate that metformin inhibits hepatic gluconeogenesis in an LKB1- and AMPK-independent manner via a decrease in hepatic energy state.
Re: Daniela Marshall-Kehrel, Cornelia Feustel, Charlotta Persson de Geeter, et al. Treatment with Propiverine in Children Suffering from Nonneurogenic Overactive Bladder and Urinary Incontinence: Results of a Randomized Placebo-Controlled Phase 3 Clinical Trial. Eur Urol 2009;55:729–38
Authors: Ferhat Ates, Ilker Akyol, Abdullah Cirakoglu
Journal: European Urology (2008)
Sight through Corneal Grafting
Authors: S. J. H. Miller
Journal: BMJ (1970)

BRIRisHwithout thrombocytopenia are also covered, followed by a section on experimental stu- dies and histopathology.Two excellent chapters containing a comprehensive review of heterophil antibody systems and the serology of infectious mononucleosis will be of interest to clinical pathologists and ex- perimental workers in the serology of this complex disease.Of special interest to phy- sicians and clinical pathologists is the chapter devoted to the problem of diagnosis in patients who do not develop heterophil antibodies.Finally, there is a character- istically thought-provoking chapter by the late Professor W. Dameshek speculating on the nature of infectious mononucleosis and its relationship to neoplastic diseases.The book is well-produced and the illus- trations are of a high standard.A minor criticism is that although the relationship of the disease to the Epstein-Barr virus is discussed, there is no illustration of this virus.The editors and authors are to be commended for their selection of data and references, as the whole makes a most authoritative book wvhich will be read and used as a reference by pathologists and physicians.
Intraarticular Gene Transfer of TNFR:Fc Suppresses Experimental Arthritis with Reduced Systemic Distribution of the Gene Product
Authors: James M.K. Chan, Gilda Villarreal, Wen Wen Jin, Tony Stepan, Haim Burstein, Sharon M. Wahl
Journal: Molecular Therapy (2002)

Tumor necrosis factor alpha (TNFalpha) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). Blockage of TNFalpha actions by systemic administration of TNF antagonists has recently been shown to ameliorate joint symptoms in RA patients. In the present study, a streptococcal cell wall (SCW)-induced rat arthritis model was used to evaluate the effect of different gene transfer routes of a TNF antagonist on the development and severity of arthritis. Successful delivery of a plasmid DNA encoding a rat TNF receptor-immunoglobulin Fc (TNFR:Fc) fusion gene prompted the subsequent administration of a recombinant adeno-associated virus (rAAV) vector encoding the antagonist, either locally (intraarticular) or systemically (intramuscular). The TNFR:Fc gene, delivered by either route, resulted in profound suppression of the arthritis as reflected in decreased inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and mRNA expression of joint proinflammatory cytokines. Increased bioactive serum TNFR levels were detected as a result of rAAV-ratTNFR:Fc administration, concomitant with a decrease in circulating TNFalpha. Administration of the rAAV-ratTNFR:Fc vector to one joint also suppressed arthritis in the contralateral joint. Importantly, intraarticular administration resulted in significantly lower systemic distribution of the gene product. Hence, the use of rAAV as the delivery vector for TNFR:Fc effectively suppressed SCW-induced arthritis and may provide an approach for local delivery of antiarthritic therapy.
New biomolecular assays must be tested by direct study in the developing world
Authors: F A Drobniewski, S M Wilson
Journal: BMJ (1998)

EDITOR—Garner et al's editorial on appropriate diagnostics in developing countries is welcome to those who develop novel diagnostic systems for tuberculosis, which remains the most important infectious disease globally.1 Conventional diagnosis is difficult, and most developments have centred on molecular amplification techniques, often using the polymerase chain reaction, which are expensive and less sensitive than culture. 2 3 Ethical issues arise if precious samples such as cerebrospinal fluid are repeatedly subdivided for research.

Per capita healthcare spending in the developed world …
Identification of NM23-H2 as a tumour-associated antigen in chronic myeloid leukaemia
Authors: S Tschiedel, C Gentilini, T Lange, C Wölfel, T Wölfel, V Lennerz, S Stevanovic, H-G Rammensee, C Huber, M Cross, D Niederwieser
Journal: Leukemia (2008)
SOCIAL NEEDS AND THE WELFARE STATE
Authors: T. Ferguson
Journal: BMJ (1958)

<b>BACKGROUND AND PURPOSE:</b> On MR imaging and CT, Japanese encephalitis (JE) shows lesions in the thalami, substantia nigra, basal ganglia, cerebral cortex, cerebellum, brain stem, and white matter, whereas temporal lobe involvement is characteristically seen in Herpes simplex encephalitis (HSE). Temporal lobe involvement in JE may cause problems in differentiating it from HSE. We undertook this study to show the temporal lobe involvement pattern in JE and highlight differentiating features from temporal lobe involvement in HSE. <b>METHODS:</b> Sixty-two patients with JE underwent CT or MR imaging or both. MR imaging was done in 53 and CT in 53. The diagnosis of JE was confirmed by cerebrospinal fluid (CSF) IgM enzyme-linked immunosorbent assay. <b>RESULTS:</b> Eleven (17.7%) patients showed temporal lobe involvement with abnormal MR imaging in all. All the patients showed hippocampal involvement. Two patients showed extension of lesions into the amygdala and uncus with insular involvement in 1. The rest of the temporal lobe was spared. All patients had thalamic and substantia nigra involvement with basal ganglia involvement in 7. Six of 9 CT scans were abnormal and the temporal lesions were seen in 2. <b>CONCLUSIONS:</b> The temporal lobe involvement pattern is fairly characteristic and mostly involves the hippocampus, usually sparing the rest of the temporal lobe. This and the concurrent involvement of the thalami, substantia nigra (SN), and basal ganglia allow differentiation from HSE. However, if the temporal lobe involvement is more severe, laboratory tests may be the only way to differentiate it from HSE, and it may be prudent to start antiviral therapy in the interim period.
Effect of Eradication of Helicobacter pylori on the Histology and Cellular Phenotype of Gastric Intestinal Metaplasia
Authors: Jiro Watari, Koushik K. Das, Peter S. Amenta, Hiroki Tanabe, Atsumi Tanaka, Xin Geng, Jim J.–C. Lin, Yutaka Kohgo, Kiron M. Das
Journal: Clinical Gastroenterology and Hepatology (2008)
Points from letters: Junior hospital staff contract
Authors: M G Rinsler
Journal: BMJ (1975)

Biological therapy with TNF-α inhibitors have been increasingly used in the treatment of inflammatory arthritis. Systemic tuberculosis infections are often known to occur following treatment with these biological agents. However, no case of periprosthetic tuberculous infection of the hip following this therapy has been reported. We report a case of a 45-year-old man who developed periprosthetic tuberculous infection soon after infliximab injection. We also discuss the need of pretreatment awareness, high index of suspicion, early diagnosis and management of such case.
TCT-668 OCT Assessment Of The Differences Between Native Coronary Atherosclerosis And Cardiac Allograft Vasculopathy
Authors: Liang Dong, Tamim Nazif, Donna Mancini, LeRoy Rabbani, Mark A. Apfelbaum, Ari T. Pollack, Kate Dalton, Gary S. Mintz, Akiko Maehara, Giora Weisz
Journal: Journal of the American College of Cardiology (2013)
Synergistic Activity of the Src Family Kinase Inhibitor Dasatinib and Oxaliplatin in Colon Carcinoma Cells Is Mediated by Oxidative Stress
Authors: Scott Kopetz, Donald P. Lesslie, Nikolas A. Dallas, Serk I. Park, Marjorie Johnson, Nila U. Parikh, Michael P. Kim, James L. Abbruzzese, Lee M. Ellis, Joya Chandra, Gary E. Gallick
Journal: Cancer Research (2009)

Chemotherapeutic regimens for the treatment of colorectal cancer generally include oxaliplatin, although inherent and acquired resistance is common. One potential mediator of oxaliplatin sensitivity is the nonreceptor protein tyrosine kinase, Src, the activity of which correlates with disease stage and patient survival. Therefore, we investigated the effects of Src inhibition using the tyrosine kinase inhibitor dasatinib on oxaliplatin sensitivity. We show that oxaliplatin acutely activates Src and that combination treatment with dasatinib is synergistic in a cell-line dependent manner, with the level of Src activation correlating with extent of synergy in a panel of six cell lines. Intracellular reactive oxygen species (ROS) are generated after oxaliplatin treatment, and ROS potently activates Src. Pretreatment with antioxidants inhibits oxaliplatin-induced Src activation. In oxaliplatin-resistant cell lines, Src activity is constitutively increased. In a mouse model of colorectal liver metastases, treatment with oxaliplatin also results in chronic Src activation. The combination of dasatinib and oxaliplatin results in significantly smaller tumors compared with single-agent treatment, corresponding with reduced proliferation and angiogenesis. Therefore, we conclude that oxaliplatin activates Src through a ROS-dependent mechanism. Src inhibition increases oxaliplatin activity both in vitro and in vivo. These results suggest that Src inhibitors combined with oxaliplatin may have efficacy in metastatic colon cancer and may provide the first indication of a molecular phenotype that might be susceptible to such combinations.
Dementia: Its Definition, Differential Diagnosis, and Subtypes
Authors: M-Marsel Mesulam
Journal: JAMA (1985)

Dementia, not unlike heart failure or renal insufficiency, is a generic term that makes little assumption about etiology. Because there are no specific laboratory tests, however, its diagnosis relies exclusively on clinical criteria. The presence of dementia should be suspected whenever mental changes of insidious onset emerge without sufficient situational stress and gradually interfere with the daily living activities that are appropriate for age and background. Dementia can be reversible or irreversible, precipitously progressive or indolent, bristling with multiple cognitive deficits, or characterized almost exclusively by disturbances of affect, motivation, and personality. When the behavioral changes are dramatic and interfere with active careers in younger individuals, early diagnosis poses little difficulty. The real challenge arises among the elderly, in whom dementia is also far more common. This is because the elderly tend to have less demanding daily activities, the disruption of which may take longer to detect, and also because
Reversal of Hypermethylation and Reactivation of <i>p16INK4a, RARβ</i>, and <i>MGMT</i> Genes by Genistein and Other Isoflavones from Soy
Authors: Ming Zhu Fang, Dapeng Chen, Yi Sun, Zhe Jin, Judith K. Christman, Chung S. Yang
Journal: Clinical Cancer Research (2005)

We have previously shown the reactivation of some methylation-silenced genes in cancer cells by (-)-epigallocatechin-3-gallate, the major polyphenol from green tea. To determine whether other polyphenolic compounds have similar activities, we studied the effects of soy isoflavones on DNA methylation.Enzyme assay was used to determine the inhibitory effect of genistein on DNA methyltransferase activity in nuclear extracts and purified recombinant enzyme. Methylation-specific PCR and quantitative real-time PCR were employed to examine the DNA methylation and gene expression status of retinoic acid receptor beta (RARbeta), p16INK4a, and O6-methylguanine methyltransferase (MGMT) in KYSE 510 esophageal squamous cell carcinoma cells treated with genistein alone or in combination with trichostatin, sulforaphane, or 2'-deoxy-5-aza-cytidine (5-aza-dCyd).Genistein (2-20 micromol/L) reversed DNA hypermethylation and reactivated RARbeta, p16INK4a, and MGMT in KYSE 510 cells. Genistein also inhibited cell growth at these concentrations. Reversal of DNA hypermethylation and reactivation of RARbeta by genistein were also observed in KYSE 150 cells and prostate cancer LNCaP and PC3 cells. Genistein (20-50 micromol/L) dose-dependently inhibited DNA methyltransferase activity, showing substrate- and methyl donor-dependent inhibition. Biochanin A and daidzein were less effective in inhibiting DNA methyltransferase activity, in reactivating RARbeta, and in inhibiting cancer cell growth. In combination with trichostatin, sulforaphane, or 5-aza-dCyd, genistein enhanced reactivation of these genes and inhibition of cell growth.These results indicate that genistein and related soy isoflavones reactivate methylation-silenced genes, partially through a direct inhibition of DNA methyltransferase, which may contribute to the chemopreventive activity of dietary isoflavones.
Visual Standards for Driving
Authors: R. W. Stephenson
Journal: BMJ (1964)

From this it seemed that the relative concen- trations of uric acid and o-tolidine might be important.By increasing the concentration of o-tolidine to five times that present in the original reagent2 (and using acetate instead of phosphate buffer) a plasma-uric-acid level of 10 mg. per 100 ml. has been found not to interfere, and a level of 20 mg. per 100 ml. to produce only a 2% underestimation.With this modified reagent, therefore, the true- glucose concentration of blood can now be estimated simply and accurately with the automatic analyser, as in the original manual method.It seems likely that similar modification of the reagents used in other published methods will produce the same results.-Iam, etc.,