tbuckley/cabot-search huggingface dataset:
Maintenance Treatment of Schizophrenia With Risperidone or Haloperidol: 2-Year Outcomes
Authors: Stephen R. Marder, Shirley M. Glynn, William C. Wirshing, Donna A. Wirshing, Doreen Ross, Clifford Widmark, Jim Mintz, Robert P. Liberman, Karen E. Blair
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Most controlled studies comparing second-generation and conventional antipsychotics have focused on the acute treatment of schizophrenia. The authors compared symptom outcomes, side effects, and social adjustment in stable schizophrenia outpatients who received 2 years of maintenance treatment with risperidone or haloperidol. METHOD: This was a 2-year, randomized, double-blind comparison of 6 mg of risperidone versus haloperidol in 63 patients with stabilized DSM-IV schizophrenia. Study patients also received 15 months of standard behavioral skills training or enhanced training with a case manager who promoted patients' use of their skills in the community. RESULTS: The risk of psychotic exacerbations and the risk of leaving the study were similar for both drug treatment groups. However, patients who received both risperidone and the enhanced community-based skills training were more likely to remain in the study than those in the other treatment groups. Patients demonstrated significant improvement in score on the Brief Psychiatric Rating Scale over time with both medications. There were no between-group differences in cluster scores for thought disturbance, hostile-suspiciousness, and withdrawal-retardation. A significant between-group difference favoring risperidone was found for the anxious-depression cluster. Risperidone resulted in significantly greater reductions in tremor and akathisia and greater improvements in most items on the SCL-90-R. CONCLUSIONS: When compared with patients given a low dose of haloperidol, risperidone-treated patients experienced similar improvements in positive and negative symptoms and similar risks of psychotic exacerbations. However, risperidone-treated patients appeared to feel subjectively better, as indicated by less anxiety and depression and fewer extrapyramidal side effects.
Prediction of Unauthorized Absence
Authors: HAROLD ALTMAN, HUGH V. ANGLE, MARJORIE L. BROWN, IVAN W. SLETTEN
Journal: American Journal of Psychiatry (1972)

A multivariate equation for predicting elopement (unauthorized absence from the hospital) was derived from 3,383 psychiatric inpatients and cross-validated with another sample, using mental status, diagnostic, and demographic data. The rate for correctly predicting elopement was 72 percent, yielding a high-risk group with a one-in-ten chance of eloping and a low-risk group with a one-in-40 chance. The authors present correlation coefficients of individual predictors of elopement and discuss these in terms of their theoretical implications.
Charge-Burping Theory Correctly Predicts Optimal Ratios of Phase Duration for Biphasic Defibrillation Waveforms
Authors: Charles D. Swerdlow, Wei Fan, James E. Brewer
Journal: Circulation (1996)

Background For biphasic waveforms, it is accepted that the ratio of the duration of phase 2 to the duration of phase 1 (phase-duration ratio) should be ≤1. The charge-burping theory postulates that the beneficial effects of phase 2 are maximal when it completely removes the charge delivered by phase 1. It predicts that the phase-duration ratio should be &lt;1 when the time constant of the defibrillation system (τ s ) exceeds the time constant of the cell membrane (τ m ) but &gt;1 when τ s &lt;τ m . This study tested the hypothesis that the optimal phase-duration ratio depends on τ s (the product of the defibrillator capacitance and pathway resistance). Methods and Results In a canine model of transvenous defibrillation (n=8), we determined stored-energy defibrillation thresholds (DFTs) for biphasic waveforms from conventional capacitors (140 μF, τ s =7.1±0.8 ms) and very small capacitors (40 μF, τ s =2.0±0.2 ms). Each capacitance was tested with phase-duration ratios of 0.5, 1, 2, and 3. The duration of phase 1 approximated the optimal monophasic waveform, 6.3±0.7 ms for 140-μF waveforms and 2.8±0.2 ms for 40-μF waveforms. For 140-μF waveforms, the DFT was lower for phase-duration ratios ≤1 than for phase-duration ratios &gt;1 ( P =.0003). The reverse was true for 40-μF capacitors ( P =.0008). There was a significant interaction between the effects of capacitance and phase-duration ratio on DFT ( P =.0002). The lowest DFT for 40-μF waveforms was less than the lowest DFT for 140-μF waveforms (4.9±2.5 versus 6.4±2.4 J, P &lt;.05). Conclusions The optimal phase-duration ratio is ≤1 for conventional capacitors and &gt;1 for small capacitors. This supports the predictions of the charge-burping theory.
Targeted disruption of cocaine-activated nucleus accumbens neurons prevents context-specific sensitization
Authors: Eisuke Koya, Sam A Golden, Brandon K Harvey, Danielle H Guez-Barber, Alexander Berkow, Danielle E Simmons, Jennifer M Bossert, Sunila G Nair, Jamie L Uejima, Marcelo T Marin, Timothy B Mitchell, David Farquhar, Sukhen C Ghosh, Brandi J Mattson, Bruce T Hope
Journal: Nature Neuroscience (2009)
Antigen- and receptor-driven regulatory mechanisms. VII. H-2-restricted anti-idiotypic suppressor factor from efferent suppressor T cells.
Authors: M H Dietz, M S Sy, B Benacerraf, A Nisonoff, M I Greene, R N Germain
Journal: The Journal of Experimental Medicine (1981)

Azobenzenearsonate (ABA)-specific T cell-derived suppressor factor (TsF1) from A/J mice was used to induced second-order suppressor T cells (Ts2). Comparison of suppressor T cells induced by antigen (Ts1) with Ts2 induced by TsF1 revealed that Ts1 were afferent suppressors active only when given at the time of antigen priming, and not thereafter, whereas Ts2 could act when transferred at any time up to 1 d before antigen challenge for a delayed-type hypersensitivity response. This was true even when the recipient could be shown to be fully immune before transfer of Ts2, thus defining these cells as efferent suppressors. The anti-idiotypic specificity of the Ts2 was demonstrated by the ability of Ts to bind to idiotype (cross-reactive idiotype [CRI])-coated Petri dishes. A soluble extract from Ts2 (TsF2) was also capable of mediating efferent suppression that was functionally antigen- (ABA) specific. Comparison of TsF1 with this new factor, TsF2, revealed that both lack Ig-constant-region determinants, possess H-2-coded determinants, and show specific binding (to ABA and to CRI+-Ig, respectively). TsF1 acts in strains that differ with respect to H-2 and background genes, whereas TsF2 shows H-2- and non-H-2-linked genetic restrictions. This existence of H-2 restriction of TsF2 activity suggests that the apparent discrepancies in studies of H-2 restriction of TsF may be a result of the analysis of two separate classes of TsF, only one of which shows genetically restricted activity, thus unifying several models of suppressor cell activity.
PM Source Apportionment for Short-Term Cardiac Function Changes in ApoE <sup>−/−</sup> Mice
Authors: Morton Lippmann, Jiang-Shiang Hwang, Polina Maciejczyk, Lung-Chi Chen
Journal: Environmental Health Perspectives (2005)

Daily rates of cardiovascular mortality and morbidity are have been associated with daily variations in fine particulate matter (aerodynamic diameter < or = 2.5 microm, PM2.5), but little is known about the influences of the individual source-related PM2.5 categories or the temporal lags for the effects. We investigated heart rate (HR) and HR variability (HRV) data collected during a 5-month study involving 6 hr/day, 5 day/week exposures of normal (C57) mice and a murine model for atherosclerotic disease (ApoE-/-) in Sterling Forest (Tuxedo, New York, USA). The mice were exposed to concentrated ambient particles (PM2.5 concentrated 10-fold, producing an average of 113 microg/m3). Daily 6-hr PM2.5 air samples were analyzed by X-ray fluorescence, permitting attribution to major PM source categories [secondary sulfate (SS), resuspended soil (RS), residual oil (RO) combustion, and other, largely due to motor vehicle traffic]. We examined associations between these PM2.5 components and both HR and HRV for three different daily time periods: during exposure, the afternoon after exposure, and late at night. For HR there were significant transient associations for RS during exposure, and for SS in the afternoon after exposure. For HRV, there were comparable associations with RO in the afternoon after exposure and for both SS and RS late at night. The biologic bases for these associations and their temporal lags are not known but may be related to the differential solubility of the biologically active PM components at the respiratory epithelia and their access to cells that release mediators that reach the cardiovascular system. Clearly, further research to elucidate the underlying processes is needed.
Attenuation of experimental autoimmune myocarditis by blocking activated T cells through inducible costimulatory molecule pathway
Authors: H Futamatsu
Journal: Cardiovascular Research (2003)

Objective: Inducible costimulator (ICOS) is a member of the CD28 family. Although inflammation is an essential pathological feature of myocarditis, the role of ICOS in myocarditis remains unclear. Methods and Results: Lewis rats were immunized on day 0 with purified porcine cardiac myosin to establish experimental autoimmune myocarditis (EAM). Flow cytometry was used to examine expression of ICOS on myocardial infiltrating cells. Anti-ICOS antibody or ICOS-immunoglobulin (ICOSIg) was administered intravenously, and rats were killed on day 14 or 21 to study effects of ICOS/ICOS-ligand (ICOSL) pathway blockade during the antigen priming phase (days 0–14) or immune response phase (days 14–21), respectively. The heart weight to body weight ratio was determined, and histological examination and echocardiogram were performed to evaluate the severity of the disease. Cytokine expression in the heart and T cell proliferation against cardiac myosin were analyzed. Flow cytometry revealed that the majority of infiltrating cells, especially CD4-positive cells, expressed ICOS. Blockade of the ICOS/ICOSL pathway during the immune response phase attenuated EAM development. However, blockade of the ICOS/ICOSL pathway during the antigen priming phase did not attenuate and exacerbate EAM. Blockade of T cell activation through ICOS suppressed expression of cytokines including INF-γ, IL-4, IL-6, IL-10, IL-1β, and TNF-α and inhibited T cell proliferation in vitro. Conclusions: Blockade of T cell activation through ICOS during the immune response phase regulates development of EAM, and therefore, ICOS may be an effective target for treating myocarditis.
Effects of continuous positive airway pressure on systemic inflammation in patients with moderate to severe obstructive sleep apnoea: a randomised controlled trial
Authors: M Kohler, L Ayers, J C T Pepperell, K L Packwood, B Ferry, N Crosthwaite, S Craig, M M Siccoli, R J O Davies, J R Stradling
Journal: Thorax (2008)

Obstructive sleep apnoea syndrome (OSAS) has been associated with cardiovascular disease in epidemiological and observational studies. Continuous positive airway pressure (CPAP) is the treatment of choice for OSAS, but the impact of this intervention on systemic inflammation involved in the atherosclerotic process remains unclear.100 men with moderate-severe OSAS were randomised to therapeutic (n = 51) or subtherapeutic (n = 49) CPAP treatment for 4 weeks to investigate the effects of active treatment on inflammatory markers such as highly sensitive C reactive protein (hsCRP), interleukin (IL)6, interferon gamma (IFNgamma) and anti-inflammatory adiponectin.4 weeks of therapeutic CPAP did not significantly change blood levels of hsCRP compared with the subtherapeutic control group (difference between median changes -0.24 mg/l (95% CI -0.88 to +0.24); p = 0.30). Plasma levels of IL6 and IFNgamma did not change significantly following therapeutic compared with subtherapeutic CPAP (difference between median changes +0.52 and -0.07 pg/ml (95% CI -0.72 to +1.94 and -0.81 to +0.44); p = 0.45 and p = 0.82, respectively). Furthermore, 4 weeks of therapeutic CPAP did not significantly change levels of adiponectin in plasma compared with the subtherapeutic control group (difference between median changes +0.05 pg/ml (95% CI -0.36 to +0.47); p = 0.84). If patients with hsCRP values above 8 mg/l at baseline were excluded, differences between the changes in hsCRP, IL6, IFNgamma and adiponectin after 4 weeks of CPAP were smaller, and again not statistically different between groups.4 weeks of CPAP treatment has no beneficial effect on blood markers of inflammation and adiponectin in patients with moderate-severe obstructive sleep apnoea.
THE MALE-SPECIFIC HISTOCOMPATIBILITY ANTIGEN, H-Y:A History of Transplantation, Immune Response Genes, Sex Determination and Expression Cloning
Authors: Elizabeth Simpson, Diane Scott, Phillip Chandler
Journal: Annual Review of Immunology (1997)

H-Y was originally discovered as a transplantation antigen. In vivo primary skin graft responses to H-Y are controlled by immune response (Ir) genes mapping to the MHC. In vitro T cell responses to H-Y are controlled by MHC class I and II Ir genes, which-respectively, restrict CD8 and CD4 T cells: These can be isolated as T cell clones in vitro. T cell receptor (TCR) transgenic mice have been made from the rearranged TCR genes of several of these, of which that specific for H-Y/Db is the best studied. Non-MHC Ir genes also contribute to the control of in vitro CTL responses to H-Y. The Hya/HYA gene(s) encoding H-Y antigen have been mapped using translocations, mutations, and deletions to Yq in humans and to the short arm of the Y chromosome in mice, where they lie in the deletion defined by the Sxrb mutation between Zfy-1 and Zfy-2. Hya/HYA has been separated from the testis-determining gene, Sry/SRY, in both humans and mice and in humans the azoospermia factor AZF has been separated from HYA. In mice transfection of cosmids and cDNAs mapping to the Sxrb deletion has identified two genes encoding H-Y peptide epitopes. Two such epitopes, H-Y/K(k) and H-Y/D(k), are encoded within different exons of Smcy and a third, H-Y/D(b), by a novel gene, Uty. Peptide elution approaches have isolated a human H-Y epitope, H-Y/HLA-B7, and identified it as a product of SMCY. Each of the Hya genes in mice is ubiquitously expressed but of unknown function. Their X chromosome homologues do not undergo X inactivation.
Electroconvulsive Therapy Augmentation in Clozapine-Resistant Schizophrenia: A Prospective, Randomized Study
Authors: Georgios Petrides, Chitra Malur, Raphael J. Braga, Samuel H. Bailine, Nina R. Schooler, Anil K. Malhotra, John M. Kane, Sohag Sanghani, Terry E. Goldberg, Majnu John, Alan Mendelowitz
Journal: American Journal of Psychiatry (2014)

Up to 70% of patients with treatment-resistant schizophrenia do not respond to clozapine. Pharmacological augmentation to clozapine has been studied with unimpressive results. The authors examined the use of ECT as an augmentation to clozapine for treatment-refractory schizophrenia.In a randomized single-blind 8-week study, patients with clozapine-resistant schizophrenia were assigned to treatment as usual (clozapine group) or a course of bilateral ECT plus clozapine (ECT plus clozapine group). Nonresponders from the clozapine group received an 8-week open trial of ECT (crossover phase). ECT was performed three times per week for the first 4 weeks and twice weekly for the last 4 weeks. Clozapine dosages remained constant. Response was defined as ≥40% reduction in symptoms based on the psychotic symptom subscale of the Brief Psychiatric Rating Scale, a Clinical Global Impressions (CGI)-severity rating <3, and a CGI-improvement rating ≤2.The intent-to-treat sample included 39 participants (ECT plus clozapine group, N=20; clozapine group, N=19). All 19 patients from the clozapine group received ECT in the crossover phase. Fifty percent of the ECT plus clozapine patients met the response criterion. None of the patients in the clozapine group met the criterion. In the crossover phase, response was 47%. There were no discernible differences between groups on global cognition. Two patients required the postponement of an ECT session because of mild confusion.The augmentation of clozapine with ECT is a safe and effective treatment option. Further research is required to determine the persistence of the improvement and the potential need for maintenance treatments.
Protective Effect of Chronic Garlic Intake on Elastic Properties of Aorta in the Elderly
Authors: Kerstin Breithaupt-Grögler, Michael Ling, Harisios Boudoulas, Gustav G. Belz
Journal: Circulation (1997)

Epidemiological studies have suggested that garlic may have protective effects against cardiovascular diseases. We undertook this cross-sectional observational study to test the hypothesis that regular garlic intake would delay the stiffening of the aorta relating to aging.We studied healthy adults (n=101; age, 50 to 80 years) who were taking > or = 300 mg/d of standardized garlic powder for > or = 2 years and 101 age- and sex-matched control subjects. Pulse wave velocity (PWV) and pressure-standardized elastic vascular resistance (EVR) were used to measure the elastic properties of the aorta. Blood pressures, heart rate, and plasma lipid levels were similar in the two groups. PWV (8.3+/-1.46 versus 9.8+/-2.45 m/s; P<.0001) and EVR (0.63+/-0.21 versus 0.9+/-0.44 m2 x s(-2) x mm Hg(-1); P<.0001) were lower in the garlic group than in the control group. PWV showed significant positive correlation with age (garlic group, r=.44; control group, r=.52) and systolic blood pressure (SBP) (garlic group, r=.48; control group, r=.54). With any degree of increase in age or SBP, PWV increased less in the garlic group than in the control group (P<.0001). ANCOVA and multiple regression analyses demonstrated that age and SBP were the most important determinants of PWV and that the effect of garlic on PWV was independent of confounding factors.Chronic garlic powder intake attenuated age-related increases in aortic stiffness. These data strongly support the hypothesis that garlic intake had a protective effect on the elastic properties of the aorta related to aging in humans.
A Mechanism-Based Antioxidant Approach for the Reduction of Skin Carcinogenesis
Authors: Yunfeng Zhao, Luksana Chaiswing, Terry D. Oberley, Ines Batinic-Haberle, William St. Clair, Charles J. Epstein, Daret St. Clair
Journal: Cancer Research (2005)

Abstract Studies in our laboratories showed that overexpression of manganese superoxide dismutase (MnSOD) reduced tumor incidence in a multistage skin carcinogenesis mouse model. However, reduction of MnSOD by heterozygous knockout of the MnSOD gene (MnSOD KO) did not lead to an increase in tumor incidence, because a reduction of MnSOD enhanced both cell proliferation and apoptosis. The present study extends our previous studies in the MnSOD KO mice and shows that apoptosis in mouse epidermis occurred prior to cell proliferation (6 versus 24 hours) when treated with tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). To investigate the possibility that a timed administration of SOD following apoptosis but before proliferation may lead to suppression of tumor incidence, we applied a SOD mimetic (MnTE-2-PyP5+) 12 hours after each TPA treatment. Biochemical studies showed that MnTE-2-PyP5+ suppressed the level of protein carbonyls and reduced the activity of activator protein-1 and the level of proliferating cellular nuclear antigen, without reducing the activity of p53 or DNA fragmentation following TPA treatment. Histologic examination confirmed that MnTE-2-PyP5+ suppressed mitosis without interfering with apoptosis. Remarkably, the incidence and multiplicity of skin tumors were reduced in mice that received MnTE-2-PyP5+ before cell proliferation. These results show a novel strategy for an antioxidant approach to cancer intervention.
The Human Genome Project and Its Impact on Psychiatry
Authors: W. Maxwell Cowan, Kathy L. Kopnisky, Steven E. Hyman
Journal: Annual Review of Neuroscience (2002)

▪ Abstract There has been substantial evidence for more than three decades that the major psychiatric illnesses such as schizophrenia, bipolar disorder, autism, and alcoholism have a strong genetic basis. During the past 15 years considerable effort has been expended in trying to establish the genetic loci associated with susceptibility to these and other mental disorders using principally linkage analysis. Despite this, only a handful of specific genes have been identified, and it is now generally recognized that further advances along these lines will require the analysis of literally hundreds of affected individuals and their families. Fortunately, the emergence in the past three years of a number of new approaches and more effective tools has given new hope to those engaged in the search for the underlying genetic and environmental factors involved in causing these illnesses, which collectively are among the most serious in all societies. Chief among these new tools is the availability of the entire human genome sequence and the prospect that within the next several years the entire complement of human genes will be known and the functions of most of their protein products elucidated. In the meantime the search for susceptibility loci is being facilitated by the availability of single nucleotide polymorphisms (SNPs) and by the beginning of haplotype mapping, which tracks the distribution of clusters of SNPs that segregate as a group. Together with high throughput DNA sequencing, microarrays for whole genome scanning, advances in proteomics, and the development of more sophisticated computer programs for analyzing sequence and association data, these advances hold promise of greatly accelerating the search for the genetic basis of most mental illnesses while, at the same time, providing molecular targets for the development of new and more effective therapies.
Triclonal gammopathy (IgAk, IgGk, and IgMk) in a patient with plasmacytoid lymphoma derived from a monoclonal origin
Authors: Takashi Murata, Hiroyuki Fujita, Hiroshi Harano, Masaya Hukawa, Heiwa Kanamori, Michio Matsuzaki, Hiroshi Mohri, Jun Kudoh, Nobuyoshi Shimizu, Takao Okubo
Journal: American Journal of Hematology (1993)

Abstract We report the case of a 64‐year‐old woman with plasma cytoid lymphoma of the ileum and gastric wall. Serum protein electrophoresis and immunoelectrophoresis showed a triclonal IgGk, IgAk, and IgMk gammopathy. Biopsy of the tumor revealed three different cell types, which were stained with antibodies specific for IgG, IgA, and IgM. However, DNA analysis of immunoglobulin gene rearrangements using J H , C μ , and C k gene probes showed a monoclonal pattern. These results suggest that the three types of malignant cells producing different classes of immunoglobulins were derived from a single clone of B‐cells that had undergone a “class switch”. © 1993 Wiley‐Liss, Inc.
Response to Letter Regarding Article, “Prevalence, Clinical Significance, and Natural History of Left Ventricular Apical Aneurysms in Hypertrophic Cardiomyopathy”
Authors: Martin S. Maron, John J. Finley, James E. Udelson, J. Martijn Bos, Michael J. Ackerman, Thomas H. Hauser, Warren J. Manning, Tammy S. Haas, John R. Lesser, Barry J. Maron
Journal: Circulation (2009)