tbuckley/cabot-search huggingface dataset:
Impairment in Holocaust survivors after 33 years: data from an unbiased community sample
Authors: W W Eaton, J J Sigal, M Weinfeld
Journal: American Journal of Psychiatry (1982)

The authors compared the psychiatric status of 135 survivors of the Holocaust with that of control subjects. This study stands apart from most previous reports in that the two groups were generated by a random sample survey of all heads of households in a community (Montreal). Survivors were more likely to have mild psychiatric symptoms regardless of the age at which they experienced the Holocaust. The difference between survivors and controls in levels of mild psychiatric symptoms was greatly amplified in those respondents who perceived a recent increase in anti-Semitism in Montreal.
Severe drug‐induced liver injury related to therapy with dimethyl fumarate
Authors: Christoph Jüngst, Yoo‐Jin Kim, Frank Lammert
Journal: Hepatology (2016)

1Department of Medicine IISaarland University Medical CenterHomburgGermany 2Institute of PathologySaarland University, Saarland University Medical CenterHomburgGermany *ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO:Christoph Jüngst, M.D.,Department of Medicine II Saarland University, Saarland University Medical Center Kirrbergerstr. 10066421 Homburg, GermanyE‐mail: [email protected]Tel: +0049‐6841‐1623223
Identification of HSP105 as a novel B-cell non-Hodgkin lymphoma (NHL) antigen (ag).
Authors: R. Zappasodi, S. Pupa, I. Bongarzone, G. C. Ghedini, L. Castagnoli, F. Miccichè, A. Cabras, C. Carlo-Stella, A. M. Gianni, M. A. Di Nicola
Journal: Journal of Clinical Oncology (2010)

e18513 Background: We reported that dendritic cell-based vaccination in relapsed indolent NHL patients achieved clinical benefits strongly associated with B and T cell responses. Hence, we exploited the antibody (Ab) repertoires of responders (R) and non-R (NR) to investigate whether the recognized ags might represent novel NHL targets for therapy. Methods: Vaccine-induced Ab cross-reactivity with allogeneic paraffin-embedded specimens and live tumor cells was tested by immunohistochemistry (IHC) and flow cytometry (FC), using biotinylated Abs purified from pre- and post-vaccine sera. Ag discovery was performed by a modified serological proteomics- based approach. Proteins differentially revealed by post-vaccine Abs of R were analyzed by mass spectrometry (MS). Abs-mediated antitumor activity of was tested in a standard proliferation assay. Statistical analysis was performed by Student t-test. Results: Post-vaccine Abs from R displayed increased allo-reactivity compared to matched pre-vaccine or NR samples and were found to significantly impair NHL cells growth (p=0.001). Towards the identification of the recognized NHL ags, western blotting analyses of follicular NHL DOHH-2 cell line with patients' Abs repeatedly revealed a differential sharp band migrating at 100-105 kDa only with post-vaccine samples from R. MS analysis identified the heat shock protein (HSP)105 in the reacting band. HSP105 was found either on the cell-surface or in the cytoplasm of a panel of B cell-NHL cell lines and normal B cells as well. Noteworthy, its expression levels increased with NHL istotype aggressiveness, whereas no reactivity was found against normal T cells or T-lymphoma cell lines. Accordingly, a commercial anti-HSP105 Ab displayed an IC50 of 8.4, 7.5 and 3.4 μ g/ml against DOHH2 cell line, diffuse large B cell lymphoma cell line SU-DHL-4 or Burkitt lymphoma cell line Namalwa, respectively. Conclusions: Our results indicate that HSP105 represents a novel immunodominant antigen of B-cell NHL as well as a new potential immunotherapeutic target. Its location on normal B cell-surface and its increasing expression with NHL aggressiveness open a new research area about HSP105 role in B-cell biology and lymphomagenesis (supported by AIRC). No significant financial relationships to disclose.
MTR-20INCREASING TUMOR TREATING FIELDS (TTFIELDS) EFFICACY IN GBM PATIENTS THROUGH OPTIMIZATION OF TRANSDUCER ARRAY CONFIGURATION
Authors: Cornelia Wenger, Ricardo Salvador, Peter J. Basser, Pedro C. Miranda
Journal: Neuro-Oncology (2015)

BACKGROUND: In 2011 Tumor Treating Fields (TTFields) were approved by the US FDA to treat recurrent glioblastoma multiforme (GBM). Recently the EF-14 Phase III clinical trial of TTFields in combination with temozolomide in patients with newly diagnosed GBM was terminated due to early success. TTFields are low-intensity (1-3 V/cm) alternating electric fields of intermediate frequencies (100-300 kHz) applied noninvasively via transducer arrays placed on the scalp. The magnitude and direction of the electric field in the tumor are crucial in determining treatment efficacy and maximizing TTField's anti-mitotic effect. METHODS: A realistic human head model was developed by segmenting MRIs into different tissue types. Virtual cystic tumors of different size and shape were placed in the brain parenchyma at different locations. The model of the commercial device used for TTFields delivery possessed an accurate current configuration and placement of the transducer arrays. The electric field was calculated using the finite element method with dielectric properties specific to 200 kHz for different tissues. RESULTS: Although the electric field distribution is highly non-uniform within the brain, the average field strength within the tumor shell exceeds 1 V/cm in all tumors for all array layouts, which is sufficiently high to inhibit cell proliferation. Comparing different array configurations shows that the induced field strength at the tumor location can always be optimized, leading to increases in average field strength of up to 184%. For optimized layouts the average field strength values can exceed 2 V/cm within the active tumor shell. CONCLUSIONS: The results of this modeling study suggest that personalized treatment planning is beneficial for optimal TTFields delivery. Adapting array layouts to individual tumor locations increases electric field strength and is predicted to improve treatment efficacy. Differences in the field distribution might also explain some of the observed variability in response among GBM patients.
2007 Russell Ross Memorial Lectureship in Vascular Biology—Epigenetic Control of Vascular Smooth Muscle Differentiation in Development and Disease
Authors: Gary K. Owens
Journal: Circulation (2007)

There is clear evidence that alterations in the differentiated state of the smooth muscle cell (SMC) play a key role in the pathogenesis of a number of major human diseases, including atherosclerosis and postan-gioplasty restenosis. This process is referred to as “phenotypic switching” and likely evolved to promote repair of vascular injury. However, the mechanisms controlling phenotypic switching as well as normal differentiation of SMCs in vivo are poorly understood. This talk will provide an overview of molecular mechanisms that control differentiation of SMCs during vascular development. A particular focus will be to consider the role of CArG elements found within the promoters of many SMC differentiation marker genes, as well as regulation of their activity by serum response factor and the potent SMC-selective serum response factor coactivator myocardin. In addition, I will summarize recent work in our laboratory showing that SMC- and gene-locus–selective changes in chromatin structure play a critical role both in normal control of SMC differentiation and in phenotypic switching in response to vascular injury. Finally, I will present evidence based on conditional knockout experiments in mice showing that krupple-like factor 4 is induced in SMCs after vascular injury and regulates SMC phenotypic switching and growth through: binding to G/C repressor elements located in close proximity of CArG elements within the promoters of many SMC marker genes, suppressing expression of myocardin, and inducing epigenetic modifications of SMC marker gene loci associated with chromatin condensation and transcriptional silencing. Supported by NIH grants P01 HL19242, R37 HL57353, and R01 HL 38854.
Production of Tumors by Methylcholanthrene and Fetal Skin Transplanted to Different Sites in Mice&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: Michael Klein
Journal: JNCI Journal of the National Cancer Institute (1951)

Journal Article Production of Tumors by Methylcholanthrene and Fetal Skin Transplanted to Different Sites in Mice Get access Michael Klein Michael Klein Research Fellow National Cancer Institute, National Institutes of Health, U. S. Public Health Service, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 11, Issue 5, April 1951, Pages 985–995, https://doi.org/10.1093/jnci/11.5.985 Published: 01 April 1951 Article history Received: 27 October 1950 Published: 01 April 1951
The Croonian Lectures on the Natural History and Pathology of Pneumonia
Authors: J. W. Washbourn
Journal: BMJ (1902)

ance of hearing, and sometimes of taste and smell, none of which were present.(b) The cortex.This would of necessity be an extensive lesion, and would involve the motor areas, causing considerable paralysis and probably twitchings.(c) The subcortical area.That is somewhere in the white matter which lies between the cortex and the internal capsule (corona radiata), and this I consider the most likely position.C. L. Dana in his study of sensory localization found that total anaesthesia was either of functional or subcortical origin.'Applying the same tests to the other prominent symptom, tho motor aphasia, I come to the same conclusion; for if the lesion had been in (a) the internal capsule, it must have been at the anterior end of the hind limb, at the genu, since it is here that the fibres to the tongue and those concerned in motor aphasia pass through.(b) T4e cortical centre concerned in motor aphasia is at the posterior end of the third left frontal convolution, bnt this is unlikely from the absence of paralysis or twitchings.We are thus again compelled to fall back upon the sub- cortical area as the mostlikelypositionforthelesion; and thiswould also account for the very slight weakness down the right side.I do not attempt to explain the inequality of the pupils, which often occurs in perfectly healthy indi- viduals.I am, therefore, of opinion that the lesion in this case was a softening in the subcortical area of the brain.This case was shown at the Liverpool Institution, in March
Behavioral and neuroendocrine responses to sodium lactate infusion in subjects with posttraumatic stress disorder
Authors: C F Jensen, T W Keller, E R Peskind, M E McFall, R C Veith, D Martin, C W Wilkinson, M A Raskind
Journal: American Journal of Psychiatry (1997)

Sodium lactate infusion has induced flashbacks accompanied by panic attacks in male combat veterans with posttraumatic stress disorder (PTSD) and concurrent panic disorder. This study addressed whether sodium lactate induces flashbacks or other intrusive PTSD symptoms in PTSD patients free of concurrent panic disorder.Behavioral, cardiovascular, catecholamine, and cortisol responses to infusion of 0.5 M sodium lactate were compared among seven subjects with PTSD without panic disorder, seven subjects with panic disorder only, and seven healthy subjects.Six of the seven PTSD subjects but no panic disorder or healthy subjects reported flashbacks or other intrusive PTSD symptoms during lactate infusion. Flashbacks were accompanied by substantial anxiety symptoms. Cortisol levels were low in the PTSD subjects.Sodium lactate induces flashbacks in persons with PTSD without comorbid panic disorder. The relationship between anxiety responses accompanying a PTSD flashback and those in a panic attack remains unclear.
Abstract IA23: Medulloblastoma subgroup-specific mutations model the tumor microenvironment
Authors: Richard J. Gilbertson
Journal: Cancer Research (2015)

Abstract Brain tumors, especially those arising in children, are remarkably heterogeneous in their response to treatment. Understanding the processes that dictate treatment sensitivity is important if we are to cure all patients. Most research has focused on identifying tumor cell intrinsic properties that regulate treatment response; but the role of the tumor microenvironment is less well understood. Here, we show that distinct subtypes of medulloblastoma possess markedly different vasculatures that are determined non-autonomously by tumor genotype, and that dictate response to systemic chemotherapy. We found that WNT-antagonists secreted by WNT-medulloblastoma – an essentially curable form of the disease – silence WNT signaling in neighboring endothelial cells, causing the formation of fenestrated and highly permeable vessels normally associated with peripheral organs: endothelial WNT signaling is essential to form and maintain the blood brain barrier (BBB). Consequently, systemically delivered chemotherapy accumulated to high levels in WNT-medulloblastomas, eliciting a marked clinical response. In contrast, while cells derived from Sonic Hedgehog (SHH)-medulloblastoma – a much less curable subtype – were intrinsically chemosenstive, they did not secrete WNT-antagonists, formed tumors with an intact, chemo-impermeable BBB and were chemoresistant in vivo. Remarkably, reactivation of WNT-signaling in WNT-medulloblastoma endothelial cells restored BBB function, rendering these tumors chemoresistant. Our data provide direct evidence that brain tumor genotype can dictate tumor vessel phenotype in a non-autonomous fashion, providing a potential explanation for the excellent prognosis of WNT-medulloblastoma. Pharmacological inhibition of endothelial WNT signaling in other primary and secondary brain tumors might enhance chemoresponsiveness by disrupting the BBB. Citation Format: Richard J. Gilbertson. Medulloblastoma subgroup-specific mutations model the tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr IA23.
Abstract IA05: Evolution of glioblastoma subtypes
Authors: Franziska Michor
Journal: Cancer Research (2015)

Abstract To understand the relationships between the non-GCIMP glioblastoma (GBM) subgroups, we performed mathematical modeling to predict the temporal sequence of driver events during tumorigenesis. The most common order of evolutionary events is 1) chromosome (chr) 7 gain and chr10 loss, followed by 2) CDKN2A loss and/or TP53 mutation, and 3) alterations canonical for specific subtypes. We then developed a computational methodology to identify drivers of broad copy number changes, identifying PDGFA (chr7) and PTEN (chr10) as driving initial nondisjunction events. These predictions were validated using mouse modeling, showing that PDGFA is sufficient to induce proneural-like gliomas and that additional NF1 loss converts proneural to the mesenchymal subtype. We further performed integrated genomic and epigenetic profiling of patient-derived cell lines to identify further genes driving subtype transformation as well as alterations in the three-dimensional architecture of the GBM genome during subtype changes. Our computational methodologies can be applied to study the evolutionary dynamics of other cancer types.
Lipid Use and Misuse by the Heart
Authors: P. Christian Schulze, Konstantinos Drosatos, Ira J. Goldberg
Journal: Circulation Research (2016)

The heart utilizes large amounts of fatty acids as energy providing substrates. The physiological balance of lipid uptake and oxidation prevents accumulation of excess lipids. Several processes that affect cardiac function, including ischemia, obesity, diabetes mellitus, sepsis, and most forms of heart failure lead to altered fatty acid oxidation and often also to the accumulation of lipids. There is now mounting evidence associating certain species of these lipids with cardiac lipotoxicity and subsequent myocardial dysfunction. Experimental and clinical data are discussed and paths to reduction of toxic lipids as a means to improve cardiac function are suggested.
Social disability in chronic psychiatric patients
Authors: J A Sylph, H E Ross, H B Kedward
Journal: American Journal of Psychiatry (1977)

The authors measured the social functioning of 147 chronic psychiatric patients using a rating scale originally devised for use with the mentally retarded, the Adaptive Behavior Scale (ABS). They found that social deficits were more widespread and generally more severe among chronic psychiatric patients than among institutionalized mentally subjects. Chronic undifferentiated schizophrenic patients showed the most comprehensive deterioration; other groups, such as neurotic patients, women, and the elderly, had more limited impairments. The authors suggest that the ABS can be useful in establishing the limits of social functioning of chronic psychiatric patients.
Oculomotor signs in a psychiatric population: a preliminary report
Authors: C N Karson
Journal: American Journal of Psychiatry (1979)

Oculomotor signs were evaluated in 172 psychiatric patients. Schizophrenic patients demonstrated a significantly higher incidence of staring, pursuit breaks, and lateral glances than did controls or other psychiatric patients. Oculomotor signs may help to differentiate schizophrenia from affective and nonpsychotic disorders. Patients with tardive dyskinesia and patients treated with tricyclic antidepressants demonstrated a significant elevation in mean blink rate. Elevated blink rates may be on early indicator of tardive dyskinesia.
Artesunate for Malaria
Authors: Paul M Arguin, Peter J Weina, Cindy P Dougherty
Journal: New England Journal of Medicine (2008)

To the Editor: Rosenthal (April 24 issue)1 presents a hypothetical case of malaria and states that there is “major concern” about the timeliness of artesunate availability because it is available rapidly only for hospitals that are near the 20 Centers for Disease Control and Prevention (CDC) quarantine stations. Artesunate is stocked at 8 of the 20 stations, which are located at major U.S. airports. To date, the timeliness of the provision of artesunate has been quite reasonable. Among the actual cases of the disease, on average it has taken only 7 hours (range, 3.5 to 15.5) from the time of the request for artesunate until the patient receives the first dose; 73% of the patients treated have been in hospitals that are not near CDC quarantine stations (average distance, 480 miles [772 km]; range, 66 to 1448 [106 to 2330]). To date, all patients treated according to this protocol have recovered. The CDC will continue to provide artesunate until it becomes a Food and Drug Administration (FDA)–approved, commercially available product and hospitals can maintain their own supply. Meanwhile, the current system can provide artesunate rapidly, and health care providers should be encouraged to access this medicine for the treatment of severe malaria.
Zika virus detection in urine from patients with Guillain-Barré syndrome on Martinique, January 2016
Authors: Benoît Rozé, Fatiha Najioullah, Jean-Louis Fergé, Kossivi Apetse, Yannick Brouste, Raymond Cesaire, Cédric Fagour, Laurence Fagour, Patrick Hochedez, Séverine Jeannin, Julien Joux, Hossein Mehdaoui, Ruddy Valentino, Aïssatou Signate, André Cabié
Journal: Eurosurveillance (2016)

We report two cases of Guillain–Barré syndrome who had concomitant Zika virus viruria. This viruria persisted for longer than 15 days after symptom onset. The cases occurred on Martinique in January 2016, at the beginning of the Zika virus outbreak. Awareness of this possible neurological complication of ZikV infection is needed.
Congenital malformations and structural developmental anomalies in groups at high risk for psychosis
Authors: T F McNeil, G Blennow, L Lundberg
Journal: American Journal of Psychiatry (1992)

Early somatic developmental anomalies may be one expression of a genetic influence toward psychosis. The purpose of this study was to investigate whether higher rates of early developmental anomalies are associated with heightened genetic risk for psychosis.Rates of congenital malformations and minor structural developmental anomalies were prospectively investigated in 84 high-risk offspring of women with histories of psychosis of nonorganic origin (schizophrenic, schizoaffective, affective, and other psychoses) and in 100 offspring of demographically similar control women with no history of psychosis. Data were collected by means of multiple physical examinations through the first 3-4 years of the offspring's lives.The rates of total congenital malformations were high, but the great majority of these malformations in both the index group and the control group represented minor physical aberrations. Rates of congenital malformations in the offspring of the index women (or any specific diagnostic subgroup of these women) were not different from those in the offspring of the control women.The inferred genetic risk for psychosis does not appear to be associated with greater rates of early somatic developmental anomalies, suggesting that early developmental anomalies do not represent an expression of genetic influence toward psychosis.
Occupational Exposure to HIV
Authors: Martin Dedicoat
Journal: New England Journal of Medicine (2003)

1091 tients with asthma or COPD and reversible bronchoconstriction; the analysis indicated that sustained use was not associated with a significant change from base line in the forced expiratory volume in one second and that long-term therapy did not increase respiratory symptoms. 1 Nevertheless, some patients with reversible airway obstruction have a negative reaction to beta-blockers; thus, caution is still appropriate, and cardioselective beta-blockers are preferred. Dr. Berend suggests a more aggressive initial pharmacologic strategy (fixed low-dose combination therapy) to treat the 50-year-old black patient with hypertension. Although fixed low-dose combination therapy has not been studied as extensively as the approach I recommend, it is gaining popularity because of the potential benefits of achieving target blood pressures sooner and the possibility that low-dose combination therapy will be associated with fewer adverse effects. I agree that his suggestion is reasonable, although it is not as well supported by data from large clinical trials. Phyllis August, M.D., M.P.H. Weill Medical College of Cornell University New York, NY 10021 paugust@med.cornell.edu
Influenzal Encephalopathy and Post-influenzal Encephalitis
Authors: J. G. Hoult, T. H. Flewett
Journal: BMJ (1960)

of the mother leading to the production of a non-viable foetus.Such an idea would be supported if it were found that the miscarriages and stillbirths prior to the pregnancy with the mongol tended to accumulate close to this event.With this in mind, the present material was examined to find whether or not there were an unexpectedly large number of conceptions ending in miscarriage in the conception order immediately prior to the mongol.The results are shown in Tables VI andVII.The difference between the observation of 15 and the expectation of 12.72 is clearly not significant.
Bringing psychiatric patients into the Medicare prospective payment system: alternatives to DRGs
Authors: J B Mitchell, B Dickey, B Liptzin, L I Sederer
Journal: American Journal of Psychiatry (1987)

The basis of Medicare's prospective payment for alcohol, drug abuse, and mental illness hospital admissions has been the patient classification system known as diagnosis-related groups (DRGs). This paper describes two alternative patient classification systems, disease staging and clinically related groups, and reports how well each system predicts resource use compared to the DRG system. Medicare data from four states were used to test the comparative strength of these patient classification systems. Although disease staging and clinically related groups performed better than DRGs, they were still poor predictors of resource use.