tbuckley/cabot-search huggingface dataset:
Psychiatric illnesses in families of subjects with schizophrenia- spectrum personality disorders: high morbidity risks for unspecified functional psychoses and schizophrenia
Authors: G Thaker, H Adami, M Moran, A Lahti, S Cassady
Journal: American Journal of Psychiatry (1993)

The authors determined morbidity risks for psychiatric illnesses in the families of probands with schizophrenia-spectrum personality disorders.Subjects were recruited from the community through newspaper advertisements. Subjects were identified as having schizophrenia-spectrum personality disorders (N = 30) if they met at least three, four, or three DSM-III-R criteria for schizoid (N = 14), schizotypal (N = 20), and/or paranoid (N = 15) personality disorder, respectively. The comparison subjects had no psychiatric diagnoses (N = 8) or had other personality disorders (N = 12); none of the subjects in either group had any DSM-III-R axis I diagnosis. Trained interviewers collected family history information about the relatives of the two groups; the interviewers were blind to the probands' diagnoses.The risks for schizophrenia, other functional psychoses, and schizophrenia-spectrum personality disorders were significantly higher in the relatives of subjects with schizophrenia-spectrum personality disorders than in the families of the comparison subjects.The high rate of schizophrenia in the families of probands with schizophrenia-spectrum personality disorders is consistent with the previous findings of higher than normal rates of these personality disorders in the biological relatives of schizophrenic patients. The significance of the high rate of unspecified functional psychoses is unclear. Use of the family study method, by which valid differential diagnosis of psychoses is possible, is indicated. The results from the current study do not rule out the possibility that the schizophrenia-spectrum personality disorders are related to psychoses in general rather than specifically to schizophrenia.
Stimulation of Spermatogenesis by Gonadotropins in Men with Hypogonadotropic Hypogonadism
Authors: David M. Finkel, Jennifer L. Phillips, Peter J. Snyder
Journal: New England Journal of Medicine (1985)

We evaluated the efficacy of gonadotropin treatment in stimulating spermatogenesis in men with hypogonadotropic hypogonadism. When 21 men with hypogonadotropic hypogonadism were treated with human chorionic gonadotropin, the sperm count increased to within the normal range in the 6 in whom hypogonadism had begun after puberty, but in only 1 of the 15 in whom it had begun before puberty (P<0.002). When the remaining 14 men with prepubertal hypogonadism were treated with human menopausal gonadotropin in addition to human chorionic gonadotropin, the sperm count increased to normal in 5 of the 7 who had not had cryptorchidism, but in only 1 of the 7 who had (P<0.05). The need for human menopausal gonadotropin as a replacement for follicle-stimulating hormone could not be predicted by pretreatment serum and urinary levels of follicle-stimulating hormone. We conclude that gonadotropin treatment will usually increase the sperm count to normal in men with hypogonadotropic hypogonadism, unless cryptorchidism has occurred. The need for human menopausal gonadotropin treatment appears to depend on the time of onset of hypogonadism. (N Engl J Med 1985; 313:651–5.)
P2-01-13: Impact of Erlotinib on MSC-Mediated TIC Expansion and EMT.
Authors: L Lacerda, T Solley, B Debeb, W Xu, S Krisnamurthy, N Ueno, J Reuben, A Klopp, W Woodward
Journal: Cancer Research (2011)

Abstract Background: Recently, we have demonstrated that mesenchymal stem cells (MSC) and MSC secreted factors (MSC-CM) have a profound effect on tumor initiating cells (TIC) enriched mammosphere formation and latency of tumor xenografts formation from breast cancer cell lines. Furthermore these interactions increased the expression of epithelial mesenchymal transition (EMT)-associated proteins which are associated with tumor cell invasion and metastasis as well as the TIC phenotype. (Klopp, A. H. et al., 2010, PLoS One. 5, e12180). Our data suggest that the presence of MSC in the tumor microenvironment may increase metastases by conferring stem progenitor cell biology on more differentiated non-metastatic cells. In addition, preliminary data suggested MSC-CM upregulated EGFR signaling in breast cancer cells. Therefore, we hypothesized that inhibiting EGFR signaling with erlotinib (tyrosin kinase inhibitor) can suppress MSC-mediated TIC expansion and EMT. Methods &amp; Results: In order to demonstrate that erlotinib inhibits MSC-CM promoted expansion of TIC, we cultured breast cancer cells lines (SUM149, SUM159, SUM190, MDA-IBC3 and MCF-7) in anchorage independent conditions with MSC-CM and treated them with increasing concentrations of erlotinib. The efficiency of mammosphere formation was examined after 5 days. We found that erlotinib inhibited MSC mediated increase in mammosphere formation in triple negative cell lines SUM149 and SUM159, and HER2−positive cell lines SUM190 and MDA-IBC3, but not in ER-positive, erlotinib resistant MCF-7 cells. Furthermore, we evaluated the impact of erlotinib on cell cultures grown with breast cancer patient-derived fluids, such as seroma and malignant pleural effusions. We observed that the effect of erlotinib on mammospheres formation was attenuated by both types of patient fluids. Discussion: Patients with triple negative breast cancer have the highest rates of metastases and no available targeted therapies for treatment. EGFR is expressed in a significant proportion of triple negative breast cancers, and recent clinical and preclinical studies suggest that EGFR may contribute to the metastasis or aggressiveness of triple negative breast cancer. Here we demonstrate that host and environmentally-derived factors are critical for determining resistance to erlotinib. In vivo studies regarding the ability of erlotininb to prevent MSC-enhanced TIC survival and metastases are underway. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-13.
PTU-182 Abdominal Pain Distinguishes Idiopathic Bile Acid Malabsorption (BAM) from Diarrhoea-Predominant Irritable Bowel Syndrome (IBS-D)
Authors: B Kok, A Mistry, R Malhotra, S Townsend, A Milestone, M Hall
Journal: Gut (2013)

<h3>Introduction</h3> Current BSG guidelines for chronic diarrhoea recommend that patients aged &lt; 45 with diarrhoea suggestive of functional disease (ie &gt; 3 months duration, no weight loss, no nocturnal symptoms, intermittent symptoms) and normal basic investigations, do not require further investigation and have IBS<sup>1</sup>. This potentially disadvantages a population who might in fact suffer with idiopathic BAM. NICE guidelines however feature abdominal pain as one of the key symptoms for diagnosing IBS<sup>2</sup>. In this observational study we aim to assess whether abdominal pain can distinguish idiopathic BAM from IBS-D. <h3>Methods</h3> All patients who underwent SeHCAT scan over a 30 month period January 2009-June 2012 were identified. Patient records and blood results/radiological imaging/endoscopy procedures performed prior to SeHCAT scan were reviewed. <h3>Results</h3> A total of 112 patients were identified. 4 patients were excluded due to the unavailability of patient records. 53 patients (49%) had abnormal bile acid retention on SeHCAT (defined by &lt; 8% retention). Of these 53 patients, 72% were female (n = 38) with a median age of 52 years (range 26–80) and average stool frequency of 7 times/day. 27 of the 53 patients (51%) had no known risk factors for BAM and the other 26 patients had risk factors (eg terminal ileal disease/ileal resection/post-cholecystectomy). Of the 55 patients classified as having normal bile acid retention ( &gt; 8% retention), 39 of the 55 (71%) had no known risk factors for BAM. Of the 39 patients who had suspected idiopathic BAM but normal SeHCAT, excluding 12 patients where there was no clear mention of abdominal pain in the notes, 78% had abdominal pain as a prominent symptom (21/27) and 22% had no pain. Of the 27 patients who had suspected idiopathic BAM and abnormal SeHCAT, excluding 7 patients where there was no mention of abdominal pain in the notes, only 40% had abdominal pain (8/20) whereas 60% had no pain (Chi-squared, p = 0.008). 20 of the 53 patients with BAM were aged &lt; 45 years old. 6 of these 20 had known risk factors for Type I BAM due to history of terminal ileal disease but the remaining 14 patients had no risk factors, fit criteria for functional disease, and could easily have been labelled as IBS-D. <h3>Conclusion</h3> Our results highlight that a significant proportion of patients with chronic diarrhoea suffer from BAM. Younger patients cannot be assumed to have ‘functional’ symptoms and though the population is small, it does seem that idiopathic BAM patients might be distinguishable from IBS-D patients in that they usually do not experience abdominal pain. <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> Thomas PD <i>et al., Gut</i> 2003; 52 (Suppl V): v1-v15 – Guidelines for the investigation of chronic diarrhoea, 2nd edition NICE guidelines on Irritable Bowel Syndrome (CG61) 2008
Non-cirrhotic portal hypertension with hypoxaemia.
Authors: J F Cadranel, J Cadranel, C Buffet, M Fabre, G Pelletier, O Ink, B Milleron, J P Etienne
Journal: Gut (1988)

The tetraspanin CD53 has been implicated in B cell development and function. CD53 is a transcriptional target of EBF1, a critical transcription factor for early B cell development. Further, human deficiency of CD53 results in recurrent infections and reduced serum Igs. Although prior studies have indicated a role for CD53 in regulating mature B cells, its role in early B cell development is not well understood. In this study, we show that CD53 expression, which is minimal on hematopoietic stem and progenitor cells, increases throughout bone marrow B cell maturation, and mice lacking CD53 have significantly decreased bone marrow, splenic, lymphatic, and peripheral B cells. Mixed bone marrow chimeras show that CD53 functions cell autonomously to promote B lymphopoiesis. <i>Cd53<sup>−/−</sup></i> mice have reduced surface expression of IL-7Rα and diminished phosphatidylinositol 3 kinase and JAK/STAT signaling in prepro- and pro-B cells. Signaling through these pathways via IL-7R is essential for early B cell survival and transition from the pro-B to pre-B cell developmental stage. Indeed, we find increased apoptosis in developing B cells and an associated reduction in pre-B and immature B cell populations in the absence of CD53. Coimmunoprecipitation and proximity ligation studies demonstrate physical interaction between CD53 and IL-7R. Together, these data, to our knowledge, suggest a novel role for CD53 during IL-7 signaling to promote early B cell differentiation.
Clinical academics welcome independent inquiry GPs' leader writes to MPs on partnership campaign Health authorities told to reverse cuts in NHS GMC given more powers to restrict a doctor's practice Intensive care beds may go on a database Guarantee given for trusts' debts Students re-examine advice on electives
Authors: L. Beecham
Journal: BMJ (1996)

# Clinical academics welcome independent inquiry {#article-title-2}

Clinical academic staff have welcomed the decision of the Committee of Vice Chancellors and Principals (CVCP) to set up an independent inquiry into the disincentives to a clinical academic career. The BMA's Medical Academic Staff Committee has offered to give evidence to the committee of inquiry, which will be chaired by Sir Rex Richards, former vice chancellor of Oxford University.

The CVCP envisages the committee investigating the problems of recruitment and retention of clinical academic staff, taking account of the changes in the NHS and in workload, in the training programmes for future specialists, in university and NHS funding systems, and the effects of European Union directives.

According to the CVCP's medical committee there were over 50 vacant established clinical chairs in universities and medical schools in 1995; 20 had been vacant for more than 12 months. Universities are also worried about the loss of posts at clinical lecturer level.

Sir Rex Richards has agreed to speak at the BMA's conference of medical academic representatives on 3 June.

# GPs' leader writes to MPs on partnership campaign {#article-title-3}

The chairman of the General Medical Services Committee has written to members of parliament to emphasise the importance of the patient education campaign, which was launched last week (2 March, p 531), and to seek their support. Dr Ian Bogle points out that some people see a need to consult their general practitioner for every problem and that inappropriate use of doctors' time can prevent them treating patients when …
Disruption of C/EBPα Function in Acute Myeloid Leukemia
Authors: Stefan Fröhling, Hartmut Döhner
Journal: New England Journal of Medicine (2004)

In acute myeloid leukemia (AML), the most common type of acute leukemia in adults, there is clonal expansion and arrested maturation of myeloid precursor cells in the bone marrow, frequently resulting in granulocytopenia, thrombocytopenia, and anemia. The genetic abnormalities underlying these events fall into distinct classes. One class arises from mutations that affect lineage-specific transcription factors involved in hematopoietic-cell differentiation.1,2 These mutations, which disrupt cellular differentiation, are crucial events in the pathogenesis of a subgroup of cases of AML. Another class of genetic events comprises mutations that affect intracellular signaling molecules in a way that enhances cell proliferation and . . .
SEVERE LIMA-LAD ANASTOMOTIC IN-STENT RESTENOSIS AND A LARGE LIMA SIDE BRANCH: WHAT WOULD YOU DO NEXT?
Authors: Vikas Aggarwal, T. Sloane Guy, Howard Cohen, Riyaz Bashir, Brian O’Neill, Grayson Wheatley, Brian O’Murchu
Journal: Journal of the American College of Cardiology (2015)
THU0339 Serum Free Light Chains: Activity Marker for Systemic Lupus Erythematosus
Authors: J. J. Jimenez, L. Campos, N. Barbosa de Carvalho, C. Hernando de Larramendi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recent studies have shown that Serum Free Light Chain (sFLC) levels correlate with Systemic Lupus Erythematosus (SLE) disease activity, a result not demonstrated for C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR). Due to the short half-life (2 -6h) of the circulating sFLC, they may be of advantage to identify changes of disease activity in comparison to other laboratory assays. <h3>Objectives</h3> Objective: to evaluate the total sFLC (∑FLC = sFLC-κ + sFLC-λ) levels in SLE patients, and compare the polyclonal sFLC increases with specific disease activity markers. <h3>Methods</h3> 79 SLE patients previously diagnosed that fulfilled at least 4 ACR criteria were studied, together with 23 control samples from unrelated patients without known rheumatologic disease. Serum protein electrophoresis was preformed to discard the presence of a monoclonal protein. Analyzed parameters: sFLC, total immunoglobulins, anti-double stranded DNA (anti-dsDNA) and anti-nuclear antibodies (ANAS), C-reactive protein (CRP), Creatinine (Cre), C3 and C4. Spearman correlations, Mann-Whitney and ANOVA analysis were done by GraphPad Prism software. <h3>Results</h3> 79 SLE patients were studied. Because SLE patient's frecuently have renal impairment that may lead to increased serum levels of sFLC, 4 patients with increased Cre were excluded from further analysis. Correlations were found between ∑FLC and Cre (r=0,2706, P=0,0181), C3 (r= -0,4070, P=0,0006) and C4 (r= -0,3179, P=0,0088). dsDNA-negative, dsDNA-positive, ANAS-negative and ANAS-positive groups' ∑FLC medians were significantly different from control median. More interestingly, the dsDNA–positive and –negative ∑FLC median were significantly different (P&lt;0,001), while it was not significant between ANAS-positive and – negative groups (P=0,2766). <h3>Conclusions</h3> The results observed indicate that the ∑sFLC may distinguish two groups within the dsDNA-positive patients. These results may suggest a potential activity marker that adds information to the patient's disease activity. Having a short half-life in the serum, the sFLC determination may allow to observe activity changes in a more timely fashion. Further prospective studies in our lab will evaluate the value of a new "activity algorithm" based on the dsDNA, C3 and C4determinations together with sFLC, needed to confirm the value of sFLC in evaluating disease activity. <h3>Disclosure of Interest</h3> None Declared
Colonic FDG Uptake Pattern in Subjects Receiving Oral Contrast With No Known or Suspected Colonic Disease
Authors: Hossein Jadvar
Journal: Clinical Nuclear Medicine (2011)

We assessed the pattern of metabolic activity in the colon of subjects who received oral contrast and had no known or suspected colonic disease.Positron emission tomography/computed tomography (PET/CT) with [F-18]-fluorodeoxyglucose was performed in 50 patients with cancer and no known or suspected colonic pathology. Studies with intense focal or segmental colonic activity (in comparison to liver reference activity), which are known to be predictive of colonic pathology were excluded. Retrospectively, colon was divided into cecum, ascending, transverse, descending, and rectosigmoid partitions, and the corresponding volumetric regions of interest were drawn on all relevant CT images. Partitioned colonic maximum standardized uptake values (SUVmax) were compared using Wilcoxon rank-sum test. Frequency of occurrence for the various colonic uptake rank orders was also tabulated.For colonic partitions, range and median SUVmax, respectively, were in decreasing order: rectosigmoid (1.5-9.9, 2.9), cecum (1.2-6.3, 2.6), ascending (0.7-4.0, 1.8), transverse (0.4-4.1, 1.2), and descending (0.6-3.1, 1.2). The SUVmax at different colonic partitions were significantly different from each other (P<0.001), except for the SUVmax between descending and transverse colonic segments (P=0.77). Combining the latter segments, the uptake rank order of "rectosigmoid>cecum>ascending" was demonstrated in 50% and "cecum>rectosigmoid>ascending" in 30% of subjects.Rectosigmoid and cecum tend to demonstrate higher metabolism than other colonic segments in the majority subjects who receive oral contrast during [F-18]-fluorodeoxyglucose positron emission tomography/CT and have no known or suspected colonic pathology.
Abstract LB-280: RNP biogenesis factor Thoc1 is targeted for ubiquitination by NEDD4-1 E3 ligase
Authors: Fei Song, Chuandong Fan, Xiaojing Zhang, Xinjiang Wang, David W. Goodrich
Journal: Cancer Research (2012)

Abstract Thoc1 encodes an essential protein component (pThoc1) of the THO complex that regulates the packaging of nascent transcripts into ribonucleoprotein complexes (RNPs). Loss of pThoc1 compromises transcriptional elongation, RNA processing, and RNA export. Up-regulation of pThoc1 expression is common in a number of different cancers relative to normal tissue (Guo et al., 2005, Yang et al., 2008) and Thoc1 is preferentially required by neoplastic cells for growth and viability (Li et al., 2007). It is unclear how Thoc1 protein or the THO complex is normally regulated. In this study we examined whether pThoc1 is modified and regulated by ubiquitination because it is a low abundant protein in normal tissue. We found that both endogenous and ectopically expressed pThoc1 are polyubiquitinylated in Hela cells. Importantly, we identified that NEDD4-1 (neural precursor cell expressed developmentally down-regulated protein 4) is an E3 ligase that can mediate pThoc1 ubiquitination. This conclusion was reached based on several lines of evidence. First, overexpression of wild type but not the enzyme-dead NEDD4-1 increased pThoc1 ubiquitination. Second, pThoc1 ubiquitination was significantly reduced in Nedd4 knock out murine embryonic fibroblasts (MEFs) compared to the wild type MEFs. Third, inducible knockdown of NEDD4-1 expression in HeLa cells caused significant reduction in pThoc1 ubiquitination. These results indicate that pThoc1 is a novel substrate of NEDD4-1 E3 ligase in cells. Regulation of pThoc1 functions by NEDD4-1 mediated ubiquitination merits further investigation. This study was supported by grant # NIH R01 CA125665 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 LB-280. doi:1538-7445.AM2012-LB-280
Maharashtra state prepares to ban smokeless tobacco use in public places from August
Authors: S. Bagcchi
Journal: BMJ (2014)

Maharashtra will become the first state in India to ban the use of smokeless tobacco in public places when a new regulation comes into force on 1 August.

Smoking in public places is already prohibited in India. However, the Maharashtra government is also banning the use of smokeless tobacco products in public places, including auditoriums, hospital buildings, railway waiting rooms, amusement …