tbuckley/cabot-search huggingface dataset:
Cannabis Use and the Course of Schizophrenia: 10-Year Follow-Up After First Hospitalization
Authors: Daniel J. Foti, Roman Kotov, Lin T. Guey, Evelyn J. Bromet
Journal: American Journal of Psychiatry (2010)

Objective The authors examined the relationship between cannabis use and the course of illness in schizophrenia over 10 years of follow-up after first psychiatric hospitalization. Method The authors assessed 229 patients with a schizophrenia spectrum disorder five times: during the first admission and 6 months, 2 years, 4 years, and 10 years later. Ratings of cannabis use and psychiatric symptoms (psychotic, negative, disorganized, and depressive) were made at each assessment. Results The lifetime rate of cannabis use was 66.2%, and survival analysis revealed that lifetime use was associated with an earlier onset of psychosis. The rates of current use ranged from 10% to 18% across assessments. Cannabis status was moderately stable, with tetrachoric correlation coefficients between waves ranging from 0.48 to 0.78. Mixed-effects logistic regression revealed that changes in cannabis use were associated with changes in psychotic symptoms over time even after gender, age, socioeconomic status, other drug use, antipsychotic medication use, and other symptoms were controlled for. Structural equation modeling indicated that the association with psychotic symptoms was bidirectional. Conclusions Cannabis use is associated with an adverse course of psychotic symptoms in schizophrenia, and vice versa, even after taking into account other clinical, substance use, and demographic variables.
Aβ-induced degradation of BMAL1 and CBP leads to circadian rhythm disruption in Alzheimer’s disease
Authors: Hyundong Song, Minho Moon, Han Kyoung Choe, Dong-Hee Han, Changhwan Jang, Ahbin Kim, Sehyung Cho, Kyungjin Kim, Inhee Mook-Jung
Journal: Molecular Neurodegeneration (2015)

Patients with Alzheimer's disease (AD) frequently experience disruption of their circadian rhythms, but whether and how circadian clock molecules are perturbed by AD remains unknown. AD is an age-related neurological disorder and amyloid-β (Aβ) is one of major causative molecules in the pathogenesis of AD.In this study, we investigated the role of Aβ in the regulation of clock molecules and circadian rhythm using an AD mouse model. These mice exhibited altered circadian behavior, and altered expression patterns of the circadian clock genes, Bmal1 and Per2. Using cultured cells, we showed that Aβ induces post-translational degradation of the circadian clock regulator CBP, as well as the transcription factor BMAL1, which forms a complex with the master circadian transcription factor CLOCK. Aβ-induced degradation of BMAL1 and CBP correlated with the reduced binding of transcription factors to the Per2 promoter, which in turn resulted in disruptions to PER2 protein expression and the oscillation of Per2 mRNA levels.Our results elucidate the underlying mechanisms for disrupted circadian rhythm in AD.
Preoperative carcinoembryonic antigen levels correlated with postoperative pathological staging in bronchial carcinoma.
Authors: J F Paone, A Kardana, G T Rogers, J Dhasmana, K Jeyasingham
Journal: Thorax (1980)

Serum carcinoembryonic antigen (CEA) levels were obtained before operation in 214 patients undergoing diagnostic tests for suspected bronchial carcinoma, and the results correlated with the postoperative, pathological stage of disease. Positive CEA levels (greater than 10 ng/ml) were observed in 40% (8/20) of stage 1, 58.5% (31/53) of stage 2, 85.2% (69/81) of stage 3, and 92.3% (24/26) of stage 4 patients with bronchial carcinoma. Furthermore, the mean CEA levels increased with stage of disease, and the differences between mean levels were found to be significant in stages 1 and 2 versus 3 and 4 (p less than 0.001). This suggests a positive correlation between the preoperative CEA level and tumour burden defined by pathological staging. When the results were compared with the histological type of lung carcinoma, CEA elevations occurred most frequently with adenocarcinoma, followed by undifferentiated and squamous cell carcinoma, reflecting perhaps the origin of this oncofetal antigen from the endodermally derived bronchial mucosa. These data indicate that preoperative serum CEA levels quantitatively reflect the extent of tumour assessed pathologically at operation and confirm the potential usefulness of this antigen as a biological tumour marker in the management of bronchial neoplasms.
Carcinogenic Effects of &lt;italic&gt;N,N&lt;/italic&gt;′-2,7-Fluorenylenebis—2,2,2-Trifluoroacetamide (2,7-FAA-F&lt;sub&gt;6&lt;/sub&gt;) Administered Orally to Buffalo Strain Rats
Authors: Harold P. Morris, Billie P. Wagner, Francis E. Ray, Harold L. Stewart, Katharine C. Snell
Journal: JNCI Journal of the National Cancer Institute (1963)

The carcinogenic effects of iV,N,N′-2,7-fluorenylenebis—2,2,2-trifluoroacetamide (2,7-FAA-F6) administered orally to rats of the Buffalo strain were studied. The results were then compared with those of previous experiments in which related compounds, in particular N,N′-2,7-fluoreny1enebisacetamide-(2,7-FAA), were tested. Compound 2,7-FAA-F6 induced tumors of the liver, mammary glands, glandular stomach, jejunum, ear structures, uterus, lung, skin, salivary glands, cranial nerves, kidney, adrenal cortex, pancreas, and hematopoietic tissues. The single tumor of the glandular stomach was a sarcoma. Lesions that were probably precancerous were induced in the glandular stomach or duodenum, but there were no definite carcinomas. In general, 2,7-FAA-F6 was less carcinogenic than 2,7-FAA when one considers the number of organs involved by tumor, the number of tumors per organ, and the degree of malignancy of the tumors induced. The only exception to this statement is that 2,7-FAA-F6 proved to be considerably more carcinogenic for the mammary gland of the female; in this respect it more nearly resembled N-2-fluorenylacetamide (2-FAA). The 2,7-FAA-F6 produced atrophy of a number of tissues and organs but was less potent in producing atrophy than 2,7-FAA.
Correlation of the glycoside response, the force staircase, and the action potential configuration in the neonatal rat heart.
Authors: G A Langer, A J Brady, S T Tan, D Serena
Journal: Circulation Research (1975)

The rat heart demonstrates marked alterations in its responses to ouabain and increased frequencies of stimulation and in the duration of its action potential during the initial 21 days of life. At an age of 6.2 days 5 times 10- minus 5M ouabain produced a 158.2% increase in dP/dt compared with a 17.2% increase at 21.1 days (P less than 0.001). At 6.2 days dP/dt increased by 53.4% when the heart rate was accelerated from 30 to 90 beats/min compared with an increase of 12.2% at 21.1 days (P less than 0.005). The positive glycoside and staircase responses at the younger age were virtually eliminated when the hearts were perfused with a solution containing 50% [Na+]o and 25% [Ca-2+]o ([Ca-2+]o/[Na+]o-2 maintained constant). The duration of the ventricular action potential progressively decreased from 350-400 msec at birth to 100-150 msec at 21 days of life. This decrease was due to a shortening and a decrease in the potential level of the plateau phase. The prominent plateau typical of the early neonatal period was significantly diminished by perfusion with 50% [Na+]o. The results suggest that Na+ flux through a slow membrane channel plays a significant role in the positive staircase and glycoside responses of the early neonatal rat heart. As the heart matures and becomes functionally anomalous relative to other mammalian species, the slow channel progressively closes.
Induction of Receptor for Advanced Glycation End Products by EBV Latent Membrane Protein 1 and Its Correlation with Angiogenesis and Cervical Lymph Node Metastasis in Nasopharyngeal Carcinoma
Authors: Akira Tsuji, Naohiro Wakisaka, Satoru Kondo, Shigeyuki Murono, Mitsuru Furukawa, Tomokazu Yoshizaki
Journal: Clinical Cancer Research (2008)

The EBV oncoprotein, latent membrane protein 1 (LMP1), contributes to the metastasis of nasopharyngeal carcinoma (NPC) by inducing factors to promote tumor invasion and angiogenesis. The receptor for advanced glycation end products (RAGE) is associated with abnormal angiogenesis in diabetic microangiopathies. Moreover, some papers have suggested the association of RAGE overexpression with tumor metastasis; thus, the associations of RAGE with LMP1 and angiogenesis in NPC were examined.Forty-two patients with NPC were evaluated for expressions of LMP1, RAGE, and S100 proteins and for microvessel counts by immunohistochemistry. Then, the RAGE induction by LMP1 was examined with Western blotting and luciferase reporter assay.The microvessel counts were significantly higher in patients with high LMP1 expression or high RAGE expression compared with cases with low expressions (P=0.0049 and P<0.0001), respectively. Patients with advanced N classification were also significantly increased in these groups (P=0.0484 and P=0.0005). The expressions of LMP1 and RAGE proteins were clearly correlated in NPC tissues (P=0.0093). Transient transfection with LMP1 expression plasmid induced RAGE protein in Ad-AH cells. The expression of LMP1 transactivated the RAGE promoter as shown by luciferase reporter assay. Mutation of the reporter at nuclear factor-kappaB binding site (-671 to -663) abolished transactivation of the RAGE promoter by LMP1.These results suggest that LMP1-induced RAGE enhances lymph node metastasis through the induction of angiogenesis in NPC. Nuclear factor-kappaB binding site (-671 to -663) is essential for transactivation of the RAGE promoter by LMP1.
THE ANGIO-SEAL EVOLUTION MULTICENTER REGISTRY: MULTIVARIATE ANALYSIS OF VASCULAR COMPLICATIONS IN HIGH RISK PATIENTS
Authors: Robert J. Applegate, Zoltan Turi, Naveen Sachdev, Abdel Ahmed, Art Szyniszewski, Malcolm Foster, Antonis Pratsos, Timothy Shapiro, Steven J. Yakubov, David M. Shavelle
Journal: Journal of the American College of Cardiology (2010)
Oncogenic Isocitrate Dehydrogenase Mutations: Mechanisms, Models, and Clinical Opportunities
Authors: Rob A. Cairns, Tak W. Mak
Journal: Cancer Discovery (2013)

Heterozygous mutations in catalytic arginine residues of isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are common in glioma, acute myeloid leukemia, chondrosarcoma, cholangiocarcinoma, and angioimmunoblastic T-cell lymphoma. The mutant enzymes acquire a neomorphic activity that converts α-ketoglutarate (α-KG) to D-2-hydroxyglutarate (D2HG), a rare metabolite. In cells and tissues expressing mutant IDH, D2HG concentrations are highly elevated. D2HG may act as an "oncometabolite" by inhibiting a class of α-KG-dependent enzymes involved in epigenetic regulation, collagen synthesis, and cell signaling. Knock-in mouse models of IDH1 mutations have shed light on these mechanisms and will provide valuable animal models for further investigation.
The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile
Authors: James Z. Huang, Warren G. Sanger, Timothy C. Greiner, Louis M. Staudt, Dennis D. Weisenburger, Diane L. Pickering, James C. Lynch, James O. Armitage, Roger A. Warnke, Ash A. Alizadeh, Izidore S. Lossos, Ronald Levy, Wing C. Chan
Journal: Blood (2002)
Constrictive pericarditis in rheumatoid arthritis.
Authors: A K Thould
Journal: Annals of the Rheumatic Diseases (1986)

Constrictive pericarditis is an unusual complication of rheumatoid arthritis, and its development appears to be uninfluenced by second-line therapy. Five patients are described who developed the disease, with possibly two more. Medical treatment is ineffective: the treatment of choice is surgical, and the postoperative prognosis is good. The crude prevalence rate for the association is 0.64% for males and 0.06% for females.
Energy metabolism and T-cell-mediated cytolysis. I. Synergism between inhibitors of respiration and glycolysis.
Authors: H R MacDonald, C J Koch
Journal: The Journal of Experimental Medicine (1977)

The energy requirements for T-cell-mediated cytolysis have been investigated. Cytolytic thymus-derived lymphocytes (CTL) were generated in vitro in mixed leukocyte cultures and assayed for cytotoxicity on 51Cr-labeled mastocytoma target cells. Cytolysis was only slightly reduced in the absence of exogenous glucose (less than 5 micrometer) or under conditions of extreme hypoxia (less than 0.2 micrometer oxygen). Furthermore, neither the glucose analogues 2-deoxy-D-glucose and 5-thio-D-glucose nor the respiratory antagonists sodium azide and 2,4-dinitrophenol were very effective inhibitors of cytolysis when used individually. However, these glucose analogues were highly effective in inhibiting cytolysis in the absence of oxygen, and the respiratory antagonists inhibited cytolysis to a much greater extent in the absence of glucose. In addition, synergistic effects were observed when the glycolytic and respiratory inhibitors were combined. Taken together, these results indicate that T-cell-mediated cytolysis is an energy-dependent process which can be supported by either oxidative or glycolytic energy pathways.
Pulmonary mechanics by spectral analysis of forced random noise.
Authors: E D Michaelson, E D Grassman, W R Peters
Journal: Journal of Clinical Investigation (1975)

The magnitude (Zrs) and phase angle (thetars) of the total respiratory impedance (Zrs), from 3 to 45 Hz, were rapidly obtained by a modification of the forced oscillation method, in which a random noise pressure wave is imposed on the respiratory system at the mouth and compared to the induced random flow using Fourier and spectral analysis. No significant amplitude or phase errors were introduced by the instrumentation. 10 normals, 5 smokers, and 5 patients with chronic obstructive lung disease (COPD) were studied. Measurements of Zrs were corrected for the parallel shunt impedance of the mouth, which was independently measured during a Valsalva maneuver, and from which the mechanical properties of the mouth were derived. There were small differences in Zrs between normals and smokers but both behaved approximately like a second-order system with thetars = 0 degree in the range of 5--9 Hz, and thetars in the range of +40 degrees at 20 Hz and +60 degrees at 40 Hz. In COPD, thetars remained more negative (compared to normals and smokers) at all frequencies and crossed 0 between 15 and 29 Hz. Changes in Zrs, similar in those in COPD, were also observed at low lung volumes in normals. These changes, the effects of a bronchodilator in COPD, and deviations of Zrs from second-order behavior in normals, can best be explained by a two-compartment parallel model, in which time-constant discrepancies between the lung parenchyma and compliant airway keep compliant greater than inertial reactance, resulting in a more negative phase angle as frequency is increased.
Work And Peak Torque During Eccentric Exercise Do Not Predict Changes In Markers Of Muscle Damage
Authors: Dale W Chapman, Michael J Newton, Zanial Zainuddin, Paul Sacco, Kazunori Nosaka
Journal: British Journal of Sports Medicine (2007)

Large inter-subject variability in responses to eccentric exercise has been reported. This study investigated the hypothesis that the variability of changes in indirect markers of exercise-induced muscle damage (EIMD) would be explained by work performed and/or torque generated during eccentric exercise.Subjects (n = 53) performed 60 maximal eccentric actions of the elbow flexors on an isokinetic dynamometer that forcibly extended the elbow joint from 60 degrees to 180 degrees at a constant velocity (90 degrees s(-1)). Markers of EIMD included maximal voluntary isometric contraction torque at 90 degrees elbow flexion (MVC), range of motion, plasma creatine kinase activity and muscle soreness. Measurements were taken 2 days before, immediately after and 1-4 days post-exercise. Pearson's correlation coefficient was used to examine relationships between exercise parameters (total work, change in total work, torque produced during exercise, change in peak torque) and markers of EIMD.Large inter-subject variability was evident for both work and torque during exercise, and changes in all markers of EIMD. Contrary to the hypothesis, total work (normalised for individual pre-exercise MVC) did not correlate significantly with any markers of EIMD, with the exception of MVC (r = 0.3). Total work performed and changes in total work showed higher correlations with some markers, but no r-values exceeded 0.4. Normalised exercise torque and the changes in peak torque during exercise were not correlated with changes in MVC, or other markers.These results suggest the large inter-subject variability in responses to eccentric exercise is not associated with work performed or torque generated during eccentric exercise.
Factual Sources of Psychiatric Patients’ Perceptions of Coercion in the Hospital Admission Process
Authors: Charles W. Lidz, Edward P. Mulvey, Steven K. Hoge, Brenda L. Kirsch, John Monahan, Marlene Eisenberg, William Gardner, Loren H. Roth
Journal: American Journal of Psychiatry (1998)

Objective: The purpose of this study was to determine what predicts patients' perceptions of coercion surrounding admission to a psychiatric hospital.Method: For 171 cases, the authors integrated data from interviews with patients, admitting clinicians, and other individuals involved in the patients' psychiatric admissions with data from the medical records. Using a structured set of procedures, coders determined whether or not nine coercion-related behaviors occurred around the time of admission. Correlation and regression analyses were used to describe the predictors of patients' scores on the MacArthur Perceived Coercion Scale.Results: The use of legal force, being given orders, threats, and "a show of force" were all strongly correlated with perceived coercion. A least squares regression accounted for 43.3% of the variance in perceived coercion. The evidence also suggested that force is typically only used in conjunction with less coercive pressures.Conclusions: Force and negative symbolic pressures, such as threats and giving orders about admission decisions, induce perceptions of coercion in persons with mental illness. Positive symbolic pressures, such as persuasion, do not induce perceptions of coercion. Such positive pressures should be tried in order to encourage admission before force or negative pressures are used. Am J Psychiatry 1998; 155: 1254-1260
Metallothionein-I/II Double Knockout Mice Are Hypersensitive to Lead-Induced Kidney Carcinogenesis
Authors: Michael P. Waalkes, Jie Liu, Robert A. Goyer, Bhalchandra A. Diwan
Journal: Cancer Research (2004)

Abstract Lead is an environmental nephrotoxicant and probable human carcinogen. Elucidating factors predisposing populations to lead toxicity is an important public health issue. Recently, we found that metallothionein-I/-II double knockout (metallothionein-null) mice that are unable to produce the major forms of metallothionein do not produce lead inclusion bodies, which are thought to mitigate lead toxicity, and were sensitive to the subchronic toxic effects of lead exposure (10 weeks), showing modestly diminished renal function and nephromegaly compared with wild-type (WT) mice. It is unclear how this knockout might impact lead carcinogenesis. Thus, the effects of lead(II) acetate were tested in groups (n = 25) of male metallothionein-null and WT mice receiving drinking water with 0, 1,000, 2,000, or 4,000 parts per million lead for up to 104 weeks. Renal proliferative lesions (adenoma and cystic tubular atypical hyperplasia) were much more common and more severe in lead-exposed metallothionein-null mice than in WT mice. A metastatic renal cell carcinoma also occurred in a lead-treated metallothionein-null mouse, whereas none occurred in WT mice. Lead-induced renal proliferative lesions showed marked overexpression of cyclin D1, a common feature of human renal tumors. Renal lead-containing nuclear inclusion bodies were frequently observed in WT mice but did not form in metallothionein-null mice. Metallothionein was often found associated with the outer portion of these inclusion bodies. Thus, the metallothionein-null mice cannot form renal inclusion bodies, even after protracted lead exposure, and this increases the carcinogenic potential of lead. Poor production of metallothionein may predispose human populations to lead carcinogenicity.
Role of nitric oxide and cyclic GMP as mediators of endothelium-independent neurogenic relaxation in bovine mesenteric artery.
Authors: J Ahlner, M E Ljusegren, N Grundström, K L Axelsson
Journal: Circulation Research (1991)

Electrical field stimulation (EFS) of phenylephrine-contracted bovine mesenteric arteries pretreated with guanethidine elicited a relaxation that amounted to roughly 40%. This relaxation was sensitive to tetrodotoxin pretreatment, suggesting a neurogenic origin. The EFS-induced relaxation was correlated to an increase in cGMP level, from 14.2 +/- 2.5 pmol/g wet wt in nonstimulated arteries to 31.6 +/- 3.4 pmol/g wet wt after 1 minute of EFS. cAMP values were not affected by EFS. Methylene blue (5 microM) and the compound LY 83583 (10 microM), inhibitors of soluble guanylate cyclase, inhibited the EFS-induced relaxation by 60% and 50%, respectively. Zaprinast (1 microM), a selective inhibitor of cGMP degradation, significantly (p = 0.005) potentiated the EFS-induced relaxation. The relaxation induced by EFS in bovine mesenteric arteries exhibits characteristics similar to the relaxations evoked by organic nitroesters and endothelium-dependent vasodilators, both of which are suggested to be mediated by cGMP and probably with nitric oxide as the common activator of the cGMP system. The possible involvement of nitric oxide as a mediator of EFS-induced relaxations was investigated with the use of known modulators of endogenous nitric oxide production. Preincubation of the arteries with 1 mM arginine or 1 mM N-alpha-benzoyl-L-arginine, both reported to potentiate endogenous nitric oxide production, or 5 mM L-canavanine, 0.25 mM NG-monomethyl-L-arginine, or 0.1 mM NG-nitro-L-arginine, alleged inhibitors of endogenous nitric oxide production, were without effect on the relaxation induced by EFS. However, pyrogallol, a generator of superoxide anions, was a potent inhibitor of relaxations induced by EFS in bovine mesenteric arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
Diagnosis of coeliac disease
Authors: R G Peter Watson
Journal: BMJ (2005)

Follow up and review are needed when test results are not clear 

T wo articles in this issue remind us about coeliac disease and the need to consider it as a diagnosis in seemingly unusual circumstances—in elderly patients and in obese patients (p 773, 775).1 2 Furthermore, in the patient reported by Saunders et al, the usual diagnostic features of anti-endomysial and anti-transglutaminase antibodies and histological enteropathy were absent initially.1

Coeliac disease is a relatively common condition. Its prevalence is approximately 0.3-1% of the population in almost all countries and ethnic groups where it has been investigated.3 Previously regarded largely as a childhood problem it is now recognised to affect mostly adults, with about 25% of patients receiving their diagnosis at over 60 years of age.4 When present, the features of malabsorption (diarrhoea and weight loss) should point to the diagnosis, but now a wide range of clinical manifestations are recognised. Patients often have few or no gastrointestinal symptoms and can even be obese.2 5

Conventionally diagnosis is based on the histological finding of …