tbuckley/cabot-search huggingface dataset:
Mice lacking caspase-2 are protected from behavioral changes, but not pathology, in the YAC128 model of Huntington disease
Authors: Jeffrey B Carroll, Amber L Southwell, Rona K Graham, Jason P Lerch, Dagmar E Ehrnhoefer, Li-Ping Cao, Wei-Ning Zhang, Yu Deng, Nagat Bissada, R Mark Henkelman, Michael R Hayden
Journal: Molecular Neurodegeneration (2011)

Huntington Disease (HD) is a neurodegenerative disorder in which caspase activation and cleavage of substrates, including the huntingtin protein, has been invoked as a pathological mechanism. Specific changes in caspase-2 (casp2) activity have been suggested to contribute to the pathogenesis of HD, however unique casp2 cleavage substrates have remained elusive. We thus utilized mice completely lacking casp2 (casp2-/-) to examine the role played by casp2 in the progression of HD. This 'substrate agnostic' approach allows us to query the effect of casp2 on HD progression without pre-defining proteolytic substrates of interest.YAC128 HD model mice lacking casp2 show protection from well-validated motor and cognitive features of HD, including performance on rotarod, swimming T-maze, pre-pulse inhibition, spontaneous alternation and locomotor tasks. However, the specific pathological features of the YAC128 mice including striatal volume loss and testicular degeneration are unaltered in mice lacking casp2. The application of high-resolution magnetic resonance imaging (MRI) techniques validates specific neuropathology in the YAC128 mice that is not altered by ablation of casp2.The rescue of behavioral phenotypes in the absence of pathological improvement suggests that different pathways may be operative in the dysfunction of neural circuitry in HD leading to behavioral changes compared to the processes leading to cell death and volume loss. Inhibition of caspase-2 activity may be associated with symptomatic improvement in HD.
Re: Modification of Clinical Presentation of Prostate Tumors by a Novel Genetic Variant in CYP3A4
Authors: Y. Ando, T. Tateishi, Y. Sekido, T. Yamamoto, T. Satoh, Y. Hasegawa, S. Kobayashi, Y. Katsumata, K. Shimokata, H. Saito
Journal: JNCI Journal of the National Cancer Institute (1999)
Status of Vaccination against Poliomyelitis, with Particular Reference to Oral Vaccination
Authors: John R. Paul
Journal: New England Journal of Medicine (1961)

THE purpose of this article is to review briefly the story that lies behind the development of live poliovirus vaccines and to report on the status of these vaccines as of December, 1960.Historical BackgroundAlmost immediately after the virus of poliomyelitis had been discovered in 19091 efforts to produce a vaccine began. Both killed and live poliovirus vaccines were tried experimentally in monkeys as early as 1910.2 In that year Dr. Simon Flexner, the Director of the Rockefeller Institute, and at that time the leading United States authority on the viral etiology of poliomyelitis, is quoted in a newspaper . . .
Lack of reflex increase in myocardial sympathetic tone after captopril: potential antianginal effect.
Authors: P Daly, B Mettauer, J L Rouleau, D Cousineau, J H Burgess
Journal: Circulation (1985)

Many vasodilators have been tried as antianginal agents, but the reflex increase in sympathetic tone produced by these drugs necessitate their use with caution in patients with angina. In the first part of this study, captopril was given to 14 patients with angina and systolic arterial pressures of greater than 120 mm Hg. Over the short term, captopril decreased arterial blood pressure (from 110 +/- 18 to 98 +/- 18 mm Hg, p less than .01) without increasing heart rate (75 +/- 15 vs 74 +/- 15 beats/min), arterial concentrations of epinephrine (0.38 +/- 0.28 vs 0.34 +/- 0.25 nM) or norepinephrine (2.7 +/- 2.1 vs 2.8 +/- 2.1 nM), or transmyocardial norepinephrine balance (216 +/- 254 vs 146 +/- 170 p mol/min). Captopril decreased average myocardial oxygen consumption (9.7 +/- 4.1 to 8.2 +/- 2.7 ml/min, p less than .01). Given over the long term (mean 5.5 months), captopril decreased the severity of angina from NYHA classification 3.0 +/- 0.8 to 1.6 +/- 0.8. In the second part of this study, captopril was given in a prospective, randomized, double-blind, placebo-controlled study to 21 patients with stable exercise-induced angina and systolic arterial pressures greater than 120 mm Hg. Captopril increased exercise time (309 +/- 137 vs 374 +/- 142 sec, p less than .05) without changing anginal threshold (rate-pressure product 17.0 +/- 6.0 vs 17.1 +/- 5.6 X 10(-3)). We conclude that captopril decreases mean arterial pressure without causing a reflex increase in myocardial sympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)
Methamphetamine Use and Schizophrenia: A Population-Based Cohort Study in California
Authors: Russell C. Callaghan, James K. Cunningham, Peter Allebeck, Tamara Arenovich, Gautam Sajeev, Gary Remington, Isabelle Boileau, Stephen J. Kish
Journal: American Journal of Psychiatry (2011)

Clinical investigators in Japan have long suggested that exposure to methamphetamine might cause a persistent schizophrenia-like psychosis. This possibility is discounted in the Western literature. To investigate the relationship between drug use and later schizophrenia, the authors conducted a large-scale cohort study of drug users initially free of persistent psychosis.A population-based cohort study was conducted using data from California inpatient hospital discharge records from 1990 through 2000. Patients with methamphetamine-related conditions (N=42,412) and those with other drug use disorders (cannabis, cocaine, alcohol, and opioids) were propensity score-matched to individuals with primary appendicitis who served as a population proxy comparison group; the methamphetamine cohort was also matched to the other drug cohorts. Cox modeling was used to estimate differences between matched groups in the rates of subsequent admission with schizophrenia diagnoses.The methamphetamine cohort had a significantly higher risk of schizophrenia than the appendicitis group (hazard ratio=9.37) and the cocaine, opioid, and alcohol groups (hazard ratios ranging from 1.46 to 2.81), but not significantly different from that of the cannabis group. The risk of schizophrenia was higher in all drug cohorts than in the appendicitis group.Study limitations include difficulty in confirming schizophrenia diagnoses independent of drug intoxication and the possibility of undetected schizophrenia predating drug exposure. The study's findings suggest that individuals with methamphetamine-related disorders have a higher risk of schizophrenia than those with other drug use disorders, with the exception of cannabis use disorders. The elevated risk in methamphetamine users may be explained by shared etiological mechanisms involved in the development of schizophrenia.
P1184 TREATMENT EFFICACY OF PEGYLATED INTERFERON PLUS RIBAVIRIN IN PATIENTS INFECTED WITH GENOTYPE 6 HEPATITIS C VIRUS
Authors: S.R. Shin, S.H. Park, M.S. Lee, J.W. Lee, J.S. Lee, Y.S. Kim, M.S. Choi, S.M. Kim, S.-H. Jeong, J.H. Shon
Journal: Journal of Hepatology (2014)
Time course of restenosis during the first year after emergency coronary stenting.
Authors: A Kastrati, A Schömig, R Dietz, F J Neumann, G Richardt
Journal: Circulation (1993)

BACKGROUND Prevention of abrupt vessel closure after percutaneous transluminal coronary angioplasty (PTCA) represents one of the current indications for intracoronary stent implantation. After the procedure, the stented segment undergoes luminal changes that may lead to late restenosis. This study was undertaken to assess the time course of luminal changes during the first year after emergency placement of coronary stents. METHODS AND RESULTS Coronary stenting was indicated in patients with present or threatened vessel closure secondary to large dissections after PTCA. From June 1989 to May 1991, 82 patients who received Palmaz-Schatz stents and did not have early vessel occlusion after stenting were enrolled into a serial angiographic follow-up study. Coronary normal reference diameter and minimal luminal diameter were measured with an automated edge detection technique. Patients who underwent repeat PTCA for restenosis were excluded from further serial angiography. The restudy rate at 3, 6, and 12 months was 96%, 81%, and 90% of the eligible patients, respectively. The incidence of restenosis (defined as a diameter stenosis &gt; or = 50%) was 22.0% at 3 months, 31.9% at 6 months, and 33.2% at 12 months. Minimal luminal diameter was increased from 0.66 +/- 0.32 mm before to 2.85 +/- 0.43 mm immediately after stenting. It was 0.46 +/- 0.31 mm smaller than the diameter of the maximally inflated balloon during the procedure. The reduction in minimal luminal diameter was 0.80 +/- 0.69 mm (p = 0.0001) for the first 3 months, 0.29 +/- 0.52 mm (p = 0.0001) between 3 and 6 months, and 0.13 +/- 0.32 mm (p = 0.01) for the last 6 months. The percentage of patients who presented a significant change in minimal luminal diameter (defined as &gt; 0.60 mm) declined from 50.6% during the first 3 months and 18.9% between 3 and 6 months to 6.5% for the period between 6 and 12 months. CONCLUSIONS The incidence and the time course of restenosis after emergency coronary stenting are similar to that reported for conventional PTCA. Coronary lumen dimensions demonstrated a peak change at 3 months and remained mostly stable after the first 6 months.
399. rAAV2 Movement Through the Late and Recycling Endosomes Is Influenced by Titer of Infection
Authors: Liang Zhang, Wei Ding, John F. Engelhardt
Journal: Molecular Therapy (2005)

Top of pageAbstract
The intracellular trafficking of recombinant adeno-associated virus type-2 (rAAV2) to the nucleus is a major barrier for efficient transduction. Using imaging and subcellular fractionation techniques, we evaluated the extent of rAAV2 movement through the late and recycling endosomes following infection in HeLa cells. The intracellular distribution of rAAV2 was monitored using expressed tagged fusion proteins for Rab7 and Rab11 that mark late and recycling endosomes, respectively. Biochemical strategies for evaluating the distribution of rAAV2 genomes in the late and recycling endosome of infected HeLa cells utilized magnetic bead immuno-isolation with ectopically expressed HA-Rab7 or HA-Rab11 endosomal tags. Results from this analysis demonstrated that the majority of AAV2 preferentially trafficked to the Rab-7 positive late endosome at an infection titer of 10 viral genomes/cell. Interestingly, at 100-fold higher titers of infection, rAAV2 movement to the Rab-11 recycling endosome increased approximately 100-fold, becoming the predominant compartment in which the virus accumulated. These results demonstrated that rAAV2 movement to the Rab-7 late endosome saturates at high titers of infection. Intracellular co-localization studies using expressed EGFP-Rab7 or EGFP-Rab11 markers and Cy3-labeled rAAV2 confirmed biochemical studies demonstrating titer-dependent trafficking patterns of rAAV2 through the recycling and late endosomal compartments. Using RNAi to inhibit either the Rab7 or Rab11 pathways, we next sought to determine which compartment might be most efficient at processing virus for functional transduction of a transgene. Results from these studies demonstrated that inhibition of Rab11 more significantly inhibited rAAV2-mediated luciferase gene expression at low titers of infection (10 viral genomes/cell), as compared to inhibition of Rab7. In summary, our findings suggest that rAAV2 trafficking through both the late and recycling endosomes can mediate functional transduction in HeLa cells. Although rAAV2 movement to the recycling endosome appears to be less efficient at low MOIs, processing of the virus through this compartment may be more effective at cellular transduction (i.e., expression of a virally encoded transgene) than through the late endosome. These findings suggest that strategies to shunt viral movement from the late to the recycling endosome may be effective at increasing the efficacy of viral transduction for gene therapy.
Cardiovascular depressant effect of protamine sulphate: experimental study and clinical implications.
Authors: M A Fadali, C A Papacostas, J J Duke, M Ledbetter, M Osbakken
Journal: Thorax (1976)

The mechanisms underlying protamine-induced hypotension and bradycardia were the subject of this investigation. Six groups of dogs with intact circulation were tested in controlled circumstances with various drugs. The following parameters were observed: femoral arterial pressure, central venous pressure, left ventricular pressure and its rate of rise, left ventricular contractile element velocity of shortening, maximal Vce, and cardiac output. The six groups were studied under these pharmacological conditions: ganglionic and adrenal medullary block with hexamethonium chlroide, postganglionic parasympathetic blockade by atropine sulphate, alpha and beta adrenergic receptor block by phenoxybenzamine and propranolol respectively, and depletion of endogenous histamine by compound 48/80 (a condensation product of p-methoxyphenethyl methylamine with formaldehyde). The last group was put on extracorporeal circulation to isolate the vascular tree from the heart. The effect of the drug on this isolated vasculature was observed by recording the femoral arterial pressure. Our findings show that the hypotension and bradycardia are produced by a direct effect of protamine on the myocardium and peripheral vascular system.
Regulation of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in human vascular smooth muscle cells.
Authors: T Couffinhal, C Duplàa, C Moreau, J M Lamazière, J Bonnet
Journal: Circulation Research (1994)

Vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin are inducible proteins involved in cell-cell adhesion. Immunohistochemical studies have indicated that human atherosclerotic plaques contain smooth muscle cells (SMCs) that express ICAM-1 and VCAM-1. Recently, we demonstrated that SMCs in culture express a functionally active cytokine-inducible ICAM-1. SMCs and mononuclear cells participate in the local accumulation of cytokines and related growth factors in atherosclerotic lesions. Therefore, we determined the effects of different cytokines and growth factors on mRNA content and cell surface expression of VCAM-1, ICAM-1, and E-selectin in cultured human aortic SMCs by Northern blotting, quantitative polymerase chain reaction amplification, and immunofluorescence flow cytometry. Under basal conditions of cultivation, both VCAM-1 mRNA and membrane expression of VCAM-1 were low and were induced very little by interleukin-1 beta (100 U/mL). Platelet-derived growth factor or transforming growth factor-beta decreased VCAM-1 mRNA basal expression. Treatment of SMCs with tumor necrosis factor-alpha (TNF-alpha) led to an increase in both VCAM-1 mRNA and cell surface expression for VCAM-1 in a dose- and time-dependent manner. Interferon-gamma induced a weak increase in VCAM-1 mRNA expression, with no synergistic effect on the stimulation by TNF-alpha. Various differences were noted between the expression of ICAM-1 and VCAM-1 genes, because interleukin-1 beta induced substantial amounts of ICAM-1 but not VCAM-1. The addition of interferon-gamma delays the time at which peak expression of ICAM-1 in response to TNF-alpha stimulation occurs. Under our conditions, we did not detect any expression of E-selectin by SMCs. These results suggest that cytokines regulate VCAM-1 and ICAM-1 expression on arterial SMCs and could play an important role in the pathophysiology of inflammatory and immune processes in atherosclerosis.
Consultation-Liaison Research: The Use of Differing Perspectives
Authors: Thomas N. Wise
Journal: Psychotherapy and Psychosomatics (1995)

Slavney and McHugh have discussed the four perspectives in psychiatry in respect to their strengths and weaknesses. Research in consultation-liaison psychiatry is reviewed by considering the various perspectives that such studies utilize. Early studies utilized the life story methodology and the disease model. The life history approach considers each patient as a unique subject whose developmental vicissitudes have meaningful associations. These studies were often viewed through a psychoanalytic theory. The disease model demands syndromal identification so that etiologic factors, whether biological, psychological or social, may eventually be discovered. More contemporary investigations use the dimensional measurement of intersubject differences that allow better designation of personality. The fourth perspective of motivated behavior offers a method of studying goal-directed activity such as substance abuse, eating pathology, and sleep disorders. Consultation-liaison studies using each framework are reviewed.
Reproduction in Hemophilia
Authors: Robert B. Francis
Journal: JAMA (1983)

Reproduction rates in 294 men with severe hemophilia, 327 of their mothers, and 215 of their sisters were compared with Vital Statistics data for the general US population matched for exact age, calendar year between 1940 and 1977, and, for women, parity. Before 1950, reproduction rates in hemophiliacs and in mothers did not differ from those of the general population, but thereafter the rates fell notably. Births to sisters who were para 0 were lower than expected beginning in 1965, but births to sisters who had had one or more nonhemophiliac children were similar to those expected of the general population. The decline in fecundity may be caused by greater availability of genetic counseling and birth control measures and by social changes. Many prospective parents would welcome the opportunity to have unafflicted children but refuse selective abortion. Preconception gender selection would be appropriate for this sex-linked disorder.
Corticosteroids and Arthritis
Authors: Richard A. Kirkpatrick, M. Thomas Stillman, Doyt L. Conn
Journal: JAMA (1975)

<h3>To the Editor.—</h3> Many patients who come to the Mayo Clinic have previously had health care elsewhere. Frequently, they have traveled to foreign countries in quest of a dramatic cure for some chronic condition. For patients who have arthritis, one of the most common places to visit is Mexicali, Mexico. Personal experiences with these clinics have been detailed elsewhere (<i>Today's Health</i>, vol 51, No. 10, October 1973, p 30). Previous analyses of the medicines prescribed there have shown them to be mixtures of corticosteroids and hormones. Recently, in one month, we saw four patients who experienced difficulties at least partially attributable to the indiscriminate use of corticosteroids in these clinics. These sequelae included withdrawal flare-ups of arthritis, neuropathy due to vasculitis, and paraplegia from epidural abscess. A fourth patient, who was to have reconstructive knee surgery, denied the use of corticosteroids, yet she was obviously cushingoid. She might have suffered
Amorolfine and itraconazole combination for severe toenail onychomycosis; results of an open randomized trial in Spain
Authors: M. Lecha
Journal: British Journal of Dermatology (2008)

In an open, randomized, clinical study of toenail onychomycosis with matrix area involvement, two alternative regimens of topical amorolfine/oral itraconazole therapy were compared with itraconazole monotherapy.A total of 131 patients were randomized to treatment. Patients in the combination groups were treated with amorolfine 5% nail lacquer (Loceryl, Galderma Laboratories) once weekly for 24 weeks and 200 mg itraconazole once daily for 6 weeks (Group AI-6) or 12 weeks (Group AI-12). A control group received itraconazole monotherapy for 12 weeks (Group 1-12). Strict inclusion criteria specified that subjects had to have onychomycosis of the toenails with matrix area involvement and/or > 80% total nail surface involvement. Mycological evaluations using both microscopic examination and culture of nail samples were performed at weeks 12 and 24. A stringent assessment of outcome at study end combined the results of mycological and clinical outcomes into a global cure rate. Safety was also assessed.At week 12, mycological cure was attained in 42 of 45 patients (93.3%) in group AI-6, 29 of 35 patients (82.9%) in group AI-12, and 14 of 34 patients in group 1-12. The difference between both combination groups and the control group were significant (P < 0.001). The global cure rate at week 24 was 83.7% (36 patients) in group AI-6, 93.9% (31 patients) in group AI-12, and 68.8% (22 patients) in group I-12. The difference between the AI-12 group and itraconazole monotherapy was significant (P < 0.05).These results indicate that amorolfine combination therapy represents an improved treatment strategy for patients with severe onychomycosis.
Fistula Connecting the Left Main Coronary Artery with the Right Atrium in a Marathon Runner
Authors: Helmut Brussee, Robert Gasser
Journal: New England Journal of Medicine (2002)

Figure 1. A 25-year-old asymptomatic marathon runner was found during a routine examination to have a continuous murmur that was more pronounced during systole and loudest at the aortic root on the right side of the sternum. Coronary angiography revealed a fistula connecting the left main coronary artery with the right atrium. Since we could not rule out the possibility that this abnormality could result in sudden death during overexertion, the patient was advised to reduce his level of physical activity. In about 55 percent of cases of coronary arteriovenous fistula, the right coronary artery or its branches are the . . .
Pseudo-Therapeutic Benefits from an Adverse Social Phenomenon (Racial Prejudice)
Authors: HERBERT A. ROBINSON
Journal: American Journal of Psychiatry (1971)

Racial prejudice is alleged to have psychological benefits in therapy: a white paranoid patient can identify with an "oppressed" black therapist. It is also said to arise during the oedipal phase of development, serving as a protective mechanism against the incest taboo. The author challenges these statements: the white paranoid's "reconstitution" is actually based on unrealistic identification, and prejudice develops before the oedipal stage, although it may appear then.
Surgical resection of pulmonary metastases. Up to what number?
Authors: P Girard, P Baldeyrou, T Le Chevalier, G Lemoine, C Tremblay, M Spielmann, D Grunenwald
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Specific results on the surgical resection of a large number of pulmonary metastases (PM) are currently unavailable, and the risk-benefit ratio of this aggressive approach may appear questionable. A systematic review of the records of 456 adult patients who underwent thoracic surgery for PM between 1979 and 1990 led to the identification of 44 patients who underwent at least one resection of eight or more PM (range eight to 110), of whom 33 (75%) had PM from osteogenic or soft tissue sarcoma. These 44 patients underwent a total of 77 operations, of which 47 (61%) were bilateral and nine (12%) incomplete resections. The 3- and 5-yr probabilities of survival after the first resection of eight or more PM were 36 and 28%, respectively, and were not significantly different from those of the 412 other patients who underwent surgery for PM over the same period. In this small group of patients, only the quality of resection (complete or incomplete) was found to be a highly significant prognostic factor (p < 0.01). A critical analysis of the reported data supports the view that, at least in patients with osteogenic or soft tissue sarcoma, the prognostic value of the number of PM seems to be more dependent on associated resectability than on the number per se and that, after careful preoperative patient selection, PM that can be resected should be resected, whatever their number.