tbuckley/cabot-search huggingface dataset:
Cortical Thinning, Functional Connectivity, and Mood-Related Impulsivity in Schizophrenia: Relationship to Aggressive Attitudes and Behavior
Authors: Matthew J. Hoptman, Daniel Antonius, Cristina J. Mauro, Emily M. Parker, Daniel C. Javitt
Journal: American Journal of Psychiatry (2014)

Aggression in schizophrenia is a major societal issue, leading to physical harm, stigmatization, patient distress, and higher health care costs. Impulsivity is associated with aggression in schizophrenia, but it is multidetermined. The subconstruct of urgency is likely to play an important role in this aggression, with positive urgency referring to rash action in the context of positive emotion, and negative urgency referring to rash action in the context of negative emotion.The authors examined urgency and its neural correlates in 33 patients with schizophrenia or schizoaffective disorder and 31 healthy comparison subjects. Urgency was measured using the Urgency, Premeditation, Perseverance, and Sensation-Seeking scale. Aggressive attitudes were measured using the Buss-Perry Aggression Questionnaire.Positive urgency, negative urgency, and aggressive attitudes were significantly and selectively elevated in schizophrenia patients (Cohen's d values, 1.21-1.50). Positive and negative urgency significantly correlated with the Aggression Questionnaire total score (r>0.48 in all cases) and each uniquely accounted for a significant portion of the variance in aggression over and above the effect of group. Urgency scores correlated with reduced cortical thickness in ventral prefrontal regions including the right frontal pole, the medial and lateral orbitofrontal gyrus and inferior frontal gyri, and the rostral anterior cingulate cortex. In patients, reduced resting-state functional connectivity in some of these regions was associated with higher urgency.These findings highlight the key role of urgency in aggressive attitudes in people with schizophrenia and suggest neural substrates of these behaviors. The results also suggest behavioral and neural targets for interventions to remediate urgency and aggression.
Anti-inflammatory effects of YopM in rheumatoid arthritis fibroblast-like synoviocytes
Authors: C. Cromme, C. Ruter, J. Scharnert, M. A. Schmidt, T. Pap, J. Bertrand
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Introduction</h3> Fibroblast-like synoviocytes (FLS) are key players in the pathogenesis of rheumatoid arthritis (RA). During the onset of the disease, they are transformed into an aggressive phenotype that sustains the joint-destructive inflammatory environment of RA. This transformation is most likely due to the combination of cytokines, growth factors and cellular interaction, which leads to the stable activated phenotype. YopM is the outer protein M of <i>Yersinia</i> species. It has cell penetrating properties and can translocate into the cell by its two N-terminal α-helices. Interestingly, YopM is capable of downregulating inflammatory response in host tissues infected with <i>Yersinia</i>. Based on these findings – self-delivering ability and anti-inflammatory properties – we investigated the effect of isolated recombinant YopM on RA-FLS. <h3>Material and methods</h3> We analysed the uptake of YopM into RA-FLS, using Cy3-coupled YopM and laser scanning microscopy. To analyse the effect of YopM on the inflammation in RA we used RA-FLS of four patients and investigated the production of MMPs and IL-6 using ELISA. Cells were preincubated with TNF-α for 24 h and then simultaneously incubated with TNF-α and YopM or treated with YopM during TNF-α stimulation without preincubation. To unravel the signalling pathways involved in the effects of YopM, we investigated the activation of MAP kinases (ERK, AKT and p-38) after stimulation with TNF-α, Il-1 and EGF and NFκB signalling by Western Blot analysis. <h3>Results</h3> In vitro, YopM penetrates the membrane of RA-FLS, is transported via vesicular structures into the cytosole and accumulates near the nucleus. When we investigated the effects of YopM on the expression of pro-inflammatory cytokines, we found a reduced expression of IL-6 after stimulation with TNF-α and incubation with YopM as compared to controls. The expression levels of MMP1 and MMP3 were significantly reduced after stimulation of RA-FLS with TNF-α and treatment with YopM in comparison with untreated controls. This reduction was also found after preincubation of the cells with TNF-α, indicating that YopM is also able to reduce an established inflammation. We investigated the mechanisms of this effect and found no differences in MAP kinases phosphorylation, but decreased phosphorylation of IκBα after stimulation with TNF-α, indicating a reduced activation of the NFκB pathway. <h3>Conclusions</h3> YopM penetrates the cell membrane of RA-FLS and reduces the inflammatory response of the cells. Therefore, it might be an effective regulator of inflammation in RA and could constitute a new therapeutic agent for the treatment of the disease.
Phase II Trial of the <i>O</i>6-Alkylguanine DNA Alkyltransferase Inhibitor <i>O</i>6-Benzylguanine and 1,3-Bis(2-Chloroethyl)-1-Nitrosourea in Advanced Melanoma
Authors: Thomas F. Gajewski, Jeffrey Sosman, Stanton L. Gerson, Lili Liu, Eileen Dolan, Shang Lin, Everett E. Vokes
Journal: Clinical Cancer Research (2005)

Abstract Purpose: 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) induces DNA damage via a chloroethyl adduct at the O6 position of guanine, which can be repaired by O6-alkylguanine DNA alkyltransferase (AGT) expressed in melanoma. We postulated that the addition of O6 benzylguanine (O6BG), a potent inactivator of AGT, would improve the clinical response to BCNU in melanoma. Experimental Design: Patients had measurable disease, adequate organ function, and a corrected Diffusing capacity of the lung for carbon monoxide (DLCO) of ≥70% predicted. They were accrued into two cohorts based on prior chemotherapy. O6BG (120 mg/m2) was administered i.v. followed by BCNU (40 mg/m2) on an outpatient basis. Peripheral blood mononuclear cells (PBMC) were collected pre- and 18 hours post-O6BG to analyze AGT depletion. Treatment was every 6 weeks, and clinical response was assessed after every two cycles. Results: Forty-two patients were enrolled, 22 of these patients were chemotherapy-naïve. In the chemotherapy-naïve cohort, there was a patient with a complete response (CR), 4 with stable disease (SD), 13 with progressive disease (PD), and 4 nonevaluable patients; the median time to progression was 80 days and the median survival was 211 days. In the prior-chemotherapy cohort, there were no responses, 3 SD, 15 PD, and 2 nonevaluable patients; median time to progression was 54 days and median survival was 120 days. AGT was depleted from PBMC in the 15 patients tested. Grades 3 to 4 myelosuppression was seen in 57% of patients; toxicities were similar between the two cohorts. Conclusions: O 6BG/BCNU was successfully administered on an outpatient basis and depleted AGT from PBMC. However, significant myelosuppression was observed and the clinical outcome was not improved. Alternative mechanisms of resistance to melanoma cell death need to be investigated.
Critical care as part of respiratory training in the UK
Authors: B C Creagh-Brown, A M. Johnston, D Pandit, R J Parker, A C Davidson
Journal: Thorax (2007)

Experience in critical care medicine is mandatory for all respiratory trainees in the UK with a need for 60 days (3 months) minimum placement in an intensive care unit (ICU). The Respiratory Critical Care Group of the British Thoracic Society1 recently reported a survey in which there was widespread agreement with this requirement, although it was inadequately provided by a number of programmes. In addition, a proportion of trainees indicated the intention to subspecialise in intensive care medicine and were concerned that their ICU experience was diluted by having responsibilities such as acute general medical takes during their attachment. We recently carried out an email survey of anaesthetic and respiratory trainees and directors of intensive care which provides additional useful information.
A comparison between the epithelial tight junction morphology of human extrapulmonary bronchi and rat trachea
Authors: RW Godfrey, NJ Severs, PK Jeffery
Journal: European Respiratory Journal (1994)

Animal models have been used to investigate the involvement of epithelial tight junctions in the pathogenesis of human airway disease. However, no previous study has compared the tight junction morphologies of human and animal species in order to relate findings in animal models to human disease. In the present study, we therefore undertook a comprehensive quantitative evaluation of tight junction morphology, to determine what similarities or differences may exist in rat and human airways. Human tissue was obtained from grossly and histologically normal extrapulmonary bronchi from lungs resected for pulmonary tumour (n = 8); rat tracheal epithelium was acquired from Sprague-Dawley specific pathogen-free animals (n = 12). The tight junction morphologies of the two species were compared with respect to junctional depth, number of strands and junctional complexity. The basic architectural arrangement of the tight junctions in both species was found to be similar; however, tight junctions in rat tissues were less deep, comprised fewer strands, and had fewer strand interconnections compared with those in the human samples. The number of strands per interconnection was similar in the two species. We conclude that, in spite of a general similarity of rat and human airway epithelial tight junctions, there are specific quantitative details of morphology which need to be considered when attempting to extrapolate to the human the results of studies of airway epithelial permeability conducted in the rat. The precise biological significance of these differences, as yet, remains unclear.
Reduction of Nightmares and Other PTSD Symptoms in Combat Veterans by Prazosin: A Placebo-Controlled Study
Authors: Murray A Raskind, Elaine R Peskind, Evan D Kanter, Eric C Petrie, Allen Radant, Charles E Thompson, Dorcas J Dobie, David Hoff, Rebekah J Rein, Kristy Straits-Tröster, Ronald G Thomas, Miles M McFall
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Prazosin is a centrally active α1 adrenergic antagonist. The authors’ goal was to evaluate prazosin efficacy for nightmares, sleep disturbance, and overall posttraumatic stress disorder (PTSD) in combat veterans. METHOD: Ten Vietnam combat veterans with chronic PTSD and severe trauma-related nightmares each received prazosin and placebo in a 20-week double-blind crossover protocol. RESULTS: Prazosin (mean dose=9.5 mg/day at bedtime, SD=0.5) was superior to placebo for the three primary outcome measures: scores on the 1) recurrent distressing dreams item and the 2) difficulty falling/staying asleep item of the Clinician-Administered PTSD Scale and 3) change in overall PTSD severity and functional status according to the Clinical Global Impression of change. Total score and symptom cluster scores for reexperiencing, avoidance/numbing, and hyperarousal on the Clinician-Administered PTSD Scale also were significantly more improved in the prazosin condition, and prazosin was well tolerated. CONCLUSIONS: These data support the efficacy of prazosin for nightmares, sleep disturbance, and other PTSD symptoms.
New approach to local thermodilution: use of pig tail catheters to avoid basic difficulties
Authors: F. MAGRINI, R. C. TARAZI
Journal: Cardiovascular Research (1977)

The use of pit tail catheters and the placing of the thermistor distal to the lumen for the cold injectate have allowed the development of a new catheter for local thermodilution with many advantages. Apart from its small size and possibility of percutaneous introduction, the spatial orientation of the thermistor to the rest of the catheter and to the port of injection ensures: (a) its absolute thermal insulation; (b) avoidance of contact with vessel walls: and (c) constant spatial relationship between the lumen for injection and the thermistor as regards the dynamics of flow and temperature change.
Tumor Cell–Derived Angiopoietin-like Protein ANGPTL2 Is a Critical Driver of Metastasis
Authors: Motoyoshi Endo, Masahiro Nakano, Tsuyoshi Kadomatsu, Shigetomo Fukuhara, Hiroaki Kuroda, Shuji Mikami, Tai Hato, Jun Aoi, Haruki Horiguchi, Keishi Miyata, Haruki Odagiri, Tetsuro Masuda, Masahiko Harada, Hirotoshi Horio, Tsunekazu Hishima, Hiroaki Nomori, Takaaki Ito, Yutaka Yamamoto, Takashi Minami, Seiji Okada, Takashi Takahashi, Naoki Mochizuki, Hirotaka Iwase, Yuichi Oike
Journal: Cancer Research (2012)

Strategies to inhibit metastasis have been mainly unsuccessful in part due to insufficient mechanistic understanding. Here, we report evidence of critical role for the angiopoietin-like protein 2 (ANGPTL2) in metastatic progression. In mice, Angptl2 has been implicated in inflammatory carcinogenesis but it has not been studied in human tumors. In patients with lung cancer, elevated levels of ANGPTL2 expression in tumor cells within the primary tumor were associated with a reduction in the period of disease-free survival after surgical resection. Transcription factors NFATc, ATF2, and c-Jun upregulated in aggressive tumor cells promoted increased Angptl2 expression. Most notably, tumor cell-derived ANGPTL2 increased in vitro motility and invasion in an autocrine/paracrine manner, conferring an aggressive metastatic tumor phenotype. In xenograft mouse models, tumor cell-derived ANGPTL2 accelerated metastasis and shortened survival whereas attenuating ANGPTL2 expression in tumor cells-blunted metastasis and extended survival. Overall, our findings showed that tumor cell-derived ANGPTL2 drives metastasis and provided an initial proof of concept for blockade of its action as a strategy to antagonize the metastatic process.
SPONTANEOUS DECREASE OF THE SURFACE TENSION OF SERUM. I
Authors: P. Lecomte du Noüy
Journal: The Journal of Experimental Medicine (1922)

1. Over 3,000 measurements of surface tension of sera have been made with the ring method, and they have yielded a new phenomenon, the spontaneous and rapid decrease of the surface tension of a serum in function of the time. 2. Generally, after 10 minutes the surface tension reaches a value which is practically constant. At least, the decrease is very much slower. After stirring, a rise occurs and a similar phenomenon takes place; but stability is not obtained as rapidly, requiring about 25 minutes. By stirring again, the same thing happens repeatedly, the slope of the curve being less marked each time, the rise in surface tension being slightly below each previous value, and the phenomenon undergoing a sort of damping. 3. An equation was established which expresses the experimental facts with an accuracy of about 0.2 per cent. It applies to the whole phenomenon, before and after stirring. It has only one characteristic constant, See PDF for Equation This formula, by simply changing t to c (concentration), expresses satisfactorily in general the phenomenon of adsorption in the surface layer; that is, the decrease in surface tension in function of the concentration. 4. Prolonged heat, at 55°C., and time seem to inhibit this phenomenon. 5. When precipitation occurs in a serum, the bottom of the liquid, which contains the precipitate, has the highest surface tension. When stirred, the surface tension rises a little every time. The upper part, clear, with lower surface tension, shows the reverse phenomenon; after every stirring, the surface tension becomes a little lower.
Vitamin D ingestion and changes to rat aorta
Authors: R VIETH
Journal: Cardiovascular Research (2002)

The recent paper by Norman et al. [1] raises alarming issues about the effect of ‘vitamin D’ in rats. Several points warrant comment or clarification from the authors.

The methods section specifies that 1,25(OH)2D was the form of ‘vitamin D’ added to the rat diets [1], and this was further supported by their reference to Mortensen et al. [2], a paper that had nothing to do with vitamin D nutrition, but instead dealt with analogs of 1,25(OH)2D. I point out that earlier rat studies, involving similar amounts of the true nutrient form of vitamin D3 (cholecalciferol) have never …
Orthotopic liver transplantation in a patient with combined hemophilia A and B
Authors: Michael A. Delorme, Paul C. Adams, David Grant, Cameron N. Ghent, Irwin R. Walker, William J. Wall
Journal: American Journal of Hematology (1990)

Abstract A 38‐year‐old man with severe factor IX and mild factor VIII deficiencies complicated by cirrhosis secondary to chronic non‐A non‐B hepatitis underwent orthotopic liver transplantation as treatment for both the cirrhosis and his congenital coagulopathy. Intraoperative hemostasis was obtained with factor VII‐depleted prothrombin complex concentrate and fresh frozen plasma. Factor VIII and factor IX levels were assayed frequently in the perioperative period, and both returned to normal within 24 hr and remained normal postoperatively. Liver transplantation can be considered as definitive therapy for hemophilia A and/or B with transfusion‐related liver disease.
Expression and localization of cyclo-oxygenase isoforms in non-small cell lung cancer
Authors: D N Watkins, J C Lenzo, A Segal, M J Garlepp, P J Thompson
Journal: European Respiratory Journal (1999)

The beneficial effects of cyclo-oxygenase (COX) inhibitors in both colon cancer and adenomatous polyps suggest a role for the prostanoid pathway in epithelial malignancy. Although variable prostanoid synthesis in non-small cell lung cancer (NSCLC) has been demonstrated in freshly obtained tissue, COX messenger ribonucleic acid (mRNA) and protein localization in such tumours had not been investigated ex vivo. Thirty-four cases of primary NSCLC were examined for both constitutive (COX-1) and inducible COX (COX-2) by means of in situ hybridization and immunohistochemistry. COX-1 mRNA expression was absent or below the level of detection via in situ hybridization. COX-1 immunohistochemistry demonstrated uniform faint cytoplasmic staining in tumour cells and stromal inflammatory cells. Semiquantitative analysis of COX-2 expression in NSCLC demonstrated the highest levels of both mRNA and protein in adenocarcinoma cells (n=10, p&lt;0.005 compared with large cell and squamous cell carcinoma), intermediate and variable expression in large cell carcinoma (n=11) and low or absent expression in squamous cell tumours (n=13). Levels of COX-2 expression in infiltrating inflammatory cells was the same in all tumour types. In conclusion, tumour cell cyclo-oxygenase-2 rather than cyclo-oxygenase-1 expression may account for the variable prostanoid production seen in non-small cell lung cancer, and primary lung adenocarcinoma expresses the highest levels of cyclooxygenase-2. Assessment of cyclo-oxygenase-2 expression ex vivo should be performed in studies examining the potential therapeutic effects of cyclo-oxygenase inhibitors in non-small cell lung cancer.
Selective Inhibition of Vascular Endothelial Growth Factor–Mediated Angiogenesis by Cyclosporin a
Authors: Gabriela L. Hernández, Olga V. Volpert, Miguel A. Íñiguez, Elisa Lorenzo, Sara Martínez-Martínez, Raquel Grau, Manuel Fresno, Juan Miguel Redondo
Journal: The Journal of Experimental Medicine (2001)

Cyclosporin A (CsA) is an immunosuppressive drug that inhibits the activity of transcription factors of the nuclear factor of activated T cells (NFAT) family, interfering with the induction of cytokines and other inducible genes required for the immune response. Here we show that CsA inhibits migration of primary endothelial cells and angiogenesis induced by vascular endothelial growth factor (VEGF); this effect appears to be mediated through the inhibition of cyclooxygenase (Cox)-2, the transcription of which is activated by VEGF in primary endothelial cells. Consistent with this, we show that the induction of Cox-2 gene expression by VEGF requires NFAT activation. Most important, the CsA-mediated inhibition of angiogenesis both in vitro and in vivo was comparable to the Cox-2 inhibitor NS-398, and reversed by prostaglandin E2. Furthermore, the in vivo corneal angiogenesis induced by VEGF, but not by basic fibroblast growth factor, was selectively inhibited in mice treated with CsA systemically. These findings involve NFAT in the regulation of Cox-2 in endothelial cells, point to a role for this transcription factor in angiogenesis, and may provide a novel mechanism underlying the beneficial effects of CsA in angiogenesis-related diseases such as rheumatoid arthritis and psoriasis.
Sacro-Iliitis in Still's Disease
Authors: Mary E. Carter
Journal: Annals of the Rheumatic Diseases (1962)

Sacro-iliitis is not generally regarded as of com- mon occurrence in adult rheumatoid arthritis, and was not a known or expected feature of the juvenile form.Because its symptoms seldom obtrude its presence is seldom excluded.In published series of cases of juvenile rheumatoid arthritis, few instances are reported, but the number of sacro-iliac x rays available is small.Thus Sairanen (1958), investi- gating particularly the radiological characteristics, reports only two cases with sacro-iliitis, but in only sixteen of his 100 cases had this region been x-rayed.In this Unit, 256 cases of Still's disease have been seen between 1947 and January 1, 1961, who fulfil the diagnostic criteria, and these have been followed at least annually on a well-defined plan.As material on these cases accumulated, our attention was drawn to the number of apparently abnormal sacro-iliac joints in pelvic films taken because of hip damage.Investigation of sacro-iliitis might contribute valuable information not only for the more complete description of Still's disease, but also on the other variants or special forms of the adult disease, that is ankylosing spondylitis, psoriatic arthropathy, and ulcerative colitis with arthritis, since few cases have been described in adolescents.In addition, because of familial association (Ansell, Bywaters, and Lawrence, unpublished), we have paid particular attention to the evaluation of sacro-iliac joint change in estimating the factors which in the adult differen- tiate ankylosing spondylitis from rheumatoid arth- ritis.To this end, pelvic films were taken of all previously-seen cases coming for follow-up and of all new cases.Before attempting to assess the incidence of abnormal sacro-iliac joints in our series, a detailed study of the normal radiological appearance of sacro-iliac joints in juveniles appeared necessary.There are few descriptions in the literature of these joints in the growing period, and the difficulty of their interpretation is stressed.A limited study was also planned to investigate
Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial
Authors: Grant Dorsey, Denise Njama, Moses R Kamya, Adithya Cattamanchi, Daniel Kyabayinze, Sarah G Staedke, Anne Gasasira, Philip J Rosenthal
Journal: The Lancet (2002)