tbuckley/cabot-search huggingface dataset:
Major histocompatibility complex-restricted self-recognition in responses to trinitrophenyl-Ficoll. A novel cell interaction pathway requiring self-recognition of accessory cell H-2 determinants by both T cells and B cells.
Authors: R J Hodes, K S Hathcock, A Singer
Journal: The Journal of Experimental Medicine (1983)

In vitro primary antibody responses to limiting concentrations of trinitrophenyl (TNP)-Ficoll were shown to be T cell dependent, requiring the cooperation of T helper (TH) cells, B cells, and accessory cells. Under these conditions, TH cells derived from long-term radiation bone marrow chimeras were major histocompatibility complex (MHC) restricted in their ability to cooperate with accessory cells expressing host-type MHC determinants. The requirement for MHC-restricted self-recognition by TNP-Ficoll-reactive B cells was assessed under these T-dependent conditions. In the presence of competent TH cells, chimeric B cells were found to be MHC restricted, cooperating only with accessory cells that expressed host-type MHC products. In contrast, the soluble products of certain monoclonal T cell lines were able to directly activate B cells in response to TNP-Ficoll, bypassing any requirement for MHC-restricted self-recognition. These findings demonstrate the existence of a novel cell interaction pathway in which B cells as well as TH cells are each required to recognize self-MHC determinants on accessory cells, but are not required to recognize each other. They further demonstrate that the requirement for self-recognition by B cells may be bypassed in certain T-dependent activation pathways.
Acute regulation by insulin of phosphatidylinositol-3-kinase, Rad, Glut 4, and lipoprotein lipase mRNA levels in human muscle.
Authors: M Laville, D Auboeuf, Y Khalfallah, N Vega, J P Riou, H Vidal
Journal: Journal of Clinical Investigation (1996)

We have investigated the acute regulation by insulin of the mRNA levels of nine genes involved in insulin action, in muscle biopsies obtained before and at the end of a 3-h euglycemic hyperinsulinemic clamp. Using reverse transcription-competitive PCR, we have measured the mRNAs encoding the two insulin receptor variants, the insulin receptor substrate-1, the p85alpha subunit of phosphatidylinositol-3-kinase, Ras associated to diabetes (Rad), the glucose transporter Glut 4, glycogen synthase, 6-phosphofructo-l-kinase, lipoprotein lipase, and the hormone-sensitive lipase. Insulin infusion induced a significant increase in the mRNA level of Glut 4 (+56 +/- 13%), Rad (+96 +/- 25%), the p85alpha subunit of phosphatidylinositol-3-kinase (+92 +/- 18%) and a decrease in the lipoprotein lipase mRNA level (-49 +/- 5%), while the abundance of the other mRNAs was unaffected. The relative expression of the two insulin receptor variants was not modified. These results demonstrate an acute coordinated regulation by insulin of the expression of genes coding key proteins involved in its action in human skeletal muscle and suggest that Rad and the p85alpha regulatory subunit of phosphatidylinositol-3-kinase can be added to the list of the genes controlled by insulin.
Gene Expression Analysis for the Prediction of Recurrence in Patients with Primary Ta Urothelial Cell Carcinoma
Authors: Iman J. Schultz, Kenneth Wester, Huub Straatman, Lambertus A. Kiemeney, Marko Babjuk, Jaroslav Mares, Johannes L. Willems, Dorine W. Swinkels, J. Alfred Witjes, Per-Uno Malmström, Jacques B. de Kok
Journal: European Urology (2006)
Suicide Attempts by Firearms and by Leaping From Heights: A Comparative Study of Survivors
Authors: Gregory M. de Moore, Andrew R. Robertson
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: The purpose of this study was to compare the clinical and demographic profiles of patients who deliberately harmed themselves, either by jumping from a great height or by using firearms, and survived. METHOD: The study consisted of an 18-year retrospective case history analysis of survivors of jumping and shooting identified from the database of consultation-liaison psychiatry referrals at a hospital in Sydney, Australia. Clinical and demographic information was collated and analyzed. RESULTS: Fifty-one patients who had shot themselves and 31 patients who had jumped, all of whom had survived, were assessed by the consultation-liaison psychiatry team. There were clear differences between the two groups. Those who jumped were more likely to be single, unemployed, and psychotic. Those who used firearms were more likely to be male, abuse alcohol, have a forensic history, and have an antisocial or borderline personality disorder. CONCLUSIONS: In this study, the subjects who attempted suicide by shooting themselves and those who did so by jumping had different profiles of mental state, personality function, and psychiatric diagnosis. The importance of mental state and specific psychiatric diagnosis as determinants of the method used has been neglected in studies of suicide. These factors should be considered along with others such as accessibility and acceptability of means, since these differences may be important when suicide prevention is considered. It is also important for psychiatrists providing consultation-liaison services to be aware of these differences in order to ensure optimal treatment of survivors.
The Role of the Thymus in Autoimmune Disease.
Authors: David W. Talmage
Journal: Annals of Internal Medicine (1964)

s1 February 1964The Role of the Thymus in Autoimmune Disease.David W. Talmage, M.D.David W. Talmage, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-2-329_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptApproximately 10 years ago, Good began a renewal of interest in the function of the thymus with the observation of an unusually high association of thymoma with agammaglobulinemia. This was followed by Metcalf's demonstration of a lymphocyte-stimulating factor in extracts of the thymus and by the demonstration that mice thymectomized at birth were relatively immunologically incompetent and possessed few lymphocytes in their lymph organs. Due to the fact that thymectomy of adult animals led to little or no depression of immunologic responsiveness and due to the absence of lymph follicles in the thymus, it was at first thought that the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: David W. Talmage, M.D.Affiliations: Denver, Colorado PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1964Volume 60, Issue 2_Part_1Page: 329-329KeywordsAutoimmune diseasesBirthLymphLymphocytesThymectomyThymomaThymus ePublished: 1 December 2008 Issue Published: 1 February 1964 PDF downloadLoading ...
Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia
Authors: Daniel C. Javitt, Robert Freedman
Journal: American Journal of Psychiatry (2014)

Sensory processing deficits, first investigated by Kraepelin and Bleuler as possible pathophysiological mechanisms in schizophrenia, are now being recharacterized in the context of our current understanding of the molecular and neurobiological brain mechanisms involved. The National Institute of Mental Health Research Domain Criteria position these deficits as intermediaries between molecular and cellular mechanisms and clinical symptoms of schizophrenia, such as hallucinations. The prepulse inhibition of startle responses by a weaker preceding tone, the inhibitory gating of response to paired sensory stimuli characterized using the auditory P50 evoked response, and the detection of slight deviations in patterns of sensory stimulation eliciting the cortical mismatch negativity potential demonstrate deficits in early sensory processing mechanisms, whose molecular and neurobiological bases are increasingly well understood. Deficits in sensory processing underlie more complex cognitive dysfunction and are in turn affected by higher-level cognitive difficulties. These deficits are now being used to identify genes involved in familial transmission of schizophrenia and to monitor potentially therapeutic drug effects for both treatment and prevention. This research also provides a clinical reminder that patients’ sensory perception of the surrounding world, even during treatment sessions, may differ considerably from others’ perceptions. A person’s ability to understand and interact effectively with the surrounding world ultimately depends on an underlying sensory experience of it.
Gail Model for Prediction of Absolute Risk of Invasive Breast Cancer: Independent Evaluation in the Florence–European Prospective Investigation Into Cancer and Nutrition Cohort
Authors: Adriano Decarli, Stefano Calza, Giovanna Masala, Claudia Specchia, Domenico Palli, Mitchell H. Gail
Journal: JNCI Journal of the National Cancer Institute (2006)

The Gail model 2 (GM) for predicting the absolute risk of invasive breast cancer has been used for counseling and to design intervention studies. Although the GM has been validated in US populations, its performance in other populations is unclear because of the wide variation in international breast cancer rates.We used data from a multicenter case-control study in Italy and from Italian cancer registries to develop a model (IT-GM) that uses the same risk factors as the GM. We evaluated the accuracy of the IT-GM and the GM using independent data from the Florence-European Prospective Investigation Into Cancer and Nutrition (EPIC) cohort. To assess model calibration (i.e., how well the model predicts the observed numbers of events in subsets of the population), we compared the number of expected incident breast cancers (E) predicted by these models with the number of observed incident breast cancers (O), and we computed the concordance statistic to measure discriminatory accuracy.The overall E/O ratios were 0.96 (95% confidence interval [CI] = 0.84 to 1.11) and 0.93 (95% CI = 0.81 to 1.08) for the IT-GM and the GM, respectively. The IT-GM was somewhat better calibrated than GM in women younger than 50 years, but the GM was better calibrated when age at first live birth categories were considered (e.g., 20- to 24-year age-at-first-birth category E/O = 0.68, 95% CI = 0.53 to 0.94 for the IT-GM and E/O = 0.75, 95% CI = 0.58 to 1.03 for the GM). The concordance statistic was approximately 59% for both models, with 95% confidence intervals indicating that the models perform statistically significantly better than pure chance (concordance statistic of 50%).There was no statistically significant evidence of miscalibration overall for either the IT-GM or the GM, and the models had equivalent discriminatory accuracy. The good performance of the IT-GM when applied on the independent data from the Florence-EPIC cohort indicates that GM can be improved for use in populations other than US populations. Our findings suggest that the Italian data may be useful for revising the GM to include additional risk factors for breast cancer.
A farnesyltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation
Authors: S. H. Yang
Journal: Journal of Clinical Investigation (2006)

Hutchinson-Gilford progeria syndrome (HGPS) is caused by the production of a truncated prelamin A, called progerin, which is farnesylated at its carboxyl terminus. Progerin is targeted to the nuclear envelope and causes misshapen nuclei. Protein farnesyltransferase inhibitors (FTI) mislocalize progerin away from the nuclear envelope and reduce the frequency of misshapen nuclei. To determine whether an FTI would ameliorate disease phenotypes in vivo, we created gene-targeted mice with an HGPS mutation (LmnaHG/+) and then examined the effect of an FTI on disease phenotypes. LmnaHG/+ mice exhibited phenotypes similar to those in human HGPS patients, including retarded growth, reduced amounts of adipose tissue, micrognathia, osteoporosis, and osteolytic lesions in bone. Osteolytic lesions in the ribs led to spontaneous bone fractures. Treatment with an FTI increased adipose tissue mass, improved body weight curves, reduced the number of rib fractures, and improved bone mineralization and bone cortical thickness. These studies suggest that FTIs could be useful for treating humans with HGPS.
PWE-220 How many biopsies at colonoscopy are required to confirm the diagnosis histologically in suspected colorectal cancer?
Authors: V Sehgal, B Krishnan, K Besherdas
Journal: Gut (2012)

<h3>Introduction</h3> Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. The prognosis depends to a large extent on the stage of disease at the time of diagnosis such that the early investigation of relevant signs and symptoms is encouraged. At present the gold-standard method for the investigation of CRC is endoscopy as it permits direct visualisation and biopsy of the lesion in question. There is little evidence on the number of biopsies needed to be obtained if a CRC is suspected macroscopically at the time of endoscopy but there is a suggestion that a minimum of six biopsies should be taken to increase the yield of an early positive diagnosis.<sup>1</sup> Patients in whom the endoscopy biopsy is non-diagnostic and cancer suspected, a repeat colonoscopy to obtain additional tissue sample is often recommended. The aims of this study were to assess whether the number of biopsies taken of suspected cancers at the time of endoscopy was proportional to the rates of positive diagnoses being made while reducing the need for a repeat endoscopic procedure to confirm or exclude cancer. <h3>Methods</h3> A retrospective analysis of all patients with suspected CRC upon endoscopy at Chase Farm Hospital over a 1-year period (2009–2010) was performed. Data were obtained from endoscopy and histopathology reports. Statistical analysis was performed using the Student t test and Fisher9s test using SPSS V.20.0 (p&lt;0.05). <h3>Results</h3> 80 patients (37 male), median age 71.5 years were investigated over the audit period. Histology revealed adenocarcinoma (ACA) 52 (65%), high-grade dysplasia (HGD) 20 (25%), normal 5 (6.3%) and other 3 (3.7%). The median number of biopsies taken of suspected cancers for the whole cohort was 6 (1–12) and 44 (55%) had six or more biopsies taken. 16 (20%) patients required at least one repeat endoscopic procedure for diagnostic purposes (initial histology was HGD in 10, 62.5%, of these patients) and histology upon repeat endoscopy demonstrated ACA in 14 (87.5%) of these patients. Patients requiring repeat endoscopy had significantly fewer biopsies (median 4.5) taken at the time of initial endoscopy compared to those who did not (median 5.5), t (76)=2.54, p&lt;0.05 using the Student t test. Patients requiring a repeat endoscopic procedure were more likely to have had less than six biopsies taken initially (11, 68.7%) compared to patients who had six or more biopsies taken (5, 31.3%) although the difference was not significant (p=0.05). <h3>Conclusion</h3> Patients who have fewer biopsies are more likely to require repeat endoscopy for histological confirmation with subsequent delays in diagnosis. We recommend obtaining a minimum of six endoscopic biopsies in patients with suspected macroscopic CRC to confirm the diagnosis histologically and prevent a repeat endoscopy. <h3>Competing interests</h3> None declared.
Prospective evaluation of endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis in 45 patients with normal conventional ultrasonography.
Authors: P Dahan, C Andant, P Levy, P Amouyal, G Amouyal, M Dumont, S Erlinger, A Sauvanet, J Belghiti, M Zins, V Vilgrain, P Bernades
Journal: Gut (1996)

The aim of this study was to prospectively evaluate endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis not detected by conventional ultrasonography. Forty five consecutive patients (26 females, 19 males, mean age: 50 years) with suspected cholecystolithiasis and at least two normal transcutaneous ultrasonography examinations were included. Endoscopic ultrasonographic criteria for the diagnosis of cholecystolithiasis were the presence of stones with or without acoustic shadowing or sludge. Criteria of microscopic examination of bile were cholesterol or bilirubinate crystals or spheroliths. Thirty three patients underwent cholecystectomy and lithiasis was found in gall bladder bile in 24. Twelve patients who were not operated on and were followed up (median: 17 months), had no evidence of cholecystolithiasis. Endoscopic ultrasonography and duodenal bile examination were 96% and 67% sensitive, respectively (p &lt; 0.03). The specificity was not different (86 and 91%, respectively). None of the 16 patients with negative results in both procedures had evidence of cholecystolithiasis. It was found that for the diagnosis of cholecystolithiasis in patients with normal conventional ultrasonography, the sensitivity of endoscopic ultrasonography is higher than that of microscopic examination of duodenal bile. If endoscopic ultrasonography and microscopic examination of duodenal bile are negative, the risk of underdiagnosing cholecystolithiasis is negligible.
Identification of individuals susceptible to high-altitude pulmonary oedema at low altitude
Authors: C. Dehnert, E. Grünig, D. Mereles, N. von Lennep, P. Bärtsch
Journal: European Respiratory Journal (2005)

Individuals susceptible to high-altitude pulmonary oedema (HAPE) are characterised by an abnormal increase of pulmonary artery systolic pressure (PASP) in hypoxia and during normoxic exercise, reduced hypoxic ventilatory response, and smaller lung volume. In 37 mountaineers with well-documented altitude tolerance, it was investigated whether any combination of these noninvasive measurements, including exercise in hypoxia, could improve the identification of HAPE-susceptible subjects at low altitude. HAPE-susceptible subjects showed a significant higher increase of PASP during hypoxia at rest (48+/-10 mmHg) compared with controls (38+/-3 mmHg), as well as during normoxic exercise (57+/-14 versus 38+/-7 mmHg) and hypoxic exercise (69+/-13 versus 49+/-8 mmHg). PASP could not be assessed in three and eight subjects during normoxic or hypoxic exercise, respectively, due to insufficient Doppler profiles or systemic arterial hypertension. Sensitivity (77-94%) and specificity (76-93%) were not significantly different between the various testing conditions. Additional assessment of hypoxic ventilatory response and lung function parameters did not improve identification of HAPE-susceptible subjects in a multivariate analysis. Due to the greater number of missing values in pulmonary artery systolic pressure measurements during hypoxic exercise, it was concluded that pulmonary artery systolic pressure measurements at rest during hypoxia or exercise in normoxia are most feasible for the identification of high-altitude pulmonary oedema-susceptible subjects.
Paradoxical shortening of scrapie incubation times by expression of prion protein transgenes derived from long incubation period mice
Authors: David Westaway, Carol A. Mirenda, Dallas Foster, Yeganeh Zebarjadian, Michael Scott, Marilyn Torchia, Shu-Lian Yang, Hana Serban, Stephen J. DeArmond, Christine Ebeling, Stanley B. Prusiner, George A. Carlson
Journal: Neuron (1991)
<i>In vitro</i> and <i>In vivo</i> Anticancer Effects of the Novel Vitamin E Ether Analogue <i>RRR</i>-α-Tocopheryloxybutyl Sulfonic Acid in Prostate Cancer
Authors: Jing Ni, Tiejun Mai, See-Tong Pang, Imranul Haque, Kaohsing Huang, Matthew A. DiMaggio, Shaozhen Xie, Nadine S. James, Dhanalakshmi Kasi, Sherry R. Chemler, Shuyuan Yeh
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Among derivatives of α-vitamin E, α-vitamin E succinate (VES), has attracted much attention due to its potent anti–prostate cancer activity in vitro and in vivo. However, the in vivo antitumor activity of VES might be compromised if administrated orally due to the VES hydrolysis by esterases in the gastrointestinal tract. Experimental Design: New nonhydrolyzable VES ether analogues were synthesized and their growth inhibition was screened by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide growth assay. Among them, RRR-α-tocopheryloxybutyl sulfonic acid (VEBSA) was further characterized by terminal deoxyribonucleotidyl transferase–mediated dUTP nick end labeling apoptosis assay, soft agar assay, and in vivo tumor formation. Results: VEBSA has potent antitumor ability, albeit to a lesser extent than VES, in in vitro cultured prostate cancer LNCaP and PC3 cells. Like VES, VEBSA induced apoptosis, repressed androgen receptor protein expression, and enhanced vitamin D receptor expression, suggesting that VEBSA can go through mechanisms similar to those used by VES to inhibit the growth of prostate cancer cells in vitro. However, 6 weeks of oral consumption of VEBSA, but not of VES, reduced the tumor burden in the xenografted prostate tumors in nude mice. Furthermore, oral intake of VEBSA for 20 weeks inhibited prostate tumor growth and progression more efficiently compared with VES in the prostate cancer tumor model of TRAMP mice. Conclusion: Oral consumption of VEBSA allows a greater anticancer activity compared with VES. Chemoprevention prefers the oral consumption of agents; the advantage of VEBSA over VES to be administrated orally will allow VEBSA to serve as an agent for both preventive and therapeutic purposes for prostate cancer.
Coeliac disease in Sudanese children.
Authors: G I Suliman
Journal: Gut (1978)

Coeliac disease has not hitherto been documented in Sudanese children. This report describes seven Sudanese children with coeliac disease of whom two are siblings. They all had evidence of impaired intestinal absorption, severe histological changes of their jejunal mucosa with clinical and histological improvement on gluten free/sorgham free diet. Subsequently one patient had a clinical relapse when gluten was reintroduced; four had positive gluten challenge using serial one hour blood xylose estimation. They all belonged to the upper socioeconomic group of the society in the north of the Sudan.
Underconstraint and overconstraint in psychiatry
Authors: Elena Bezzubova, Gordon Globus
Journal: Behavioral and Brain Sciences (2004)

Hallucination lies at an intriguing border between psychiatry and philosophy. Although Behrendt &amp; Young (B&amp;Y) tie their proposal to Kantian transcendental idealism, other philosophical positions are equally consistent. Cognition is underconstrained by reality not only in hallucination but also in autism and dreaming. Sensory underconstraint is insufficient to encompass schizophrenia. There is also a breakdown in integrative capacity on the cognitive side. From a wider clinical perspective than schizophrenia, there can be underconstraint or overconstraint in sensory and cognitive functionalities.