bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26
Authors: Eltzschig Holger K. , Faigle Marion , Knapp Simone , Karhausen Jorn , Ibla Juan , Rosenberger Peter , Odegard Kirsten C. , Laussen Peter C. , Thompson Linda F. , Colgan Sean P.
Published: May 2006

Extracellular levels of adenosine increase during hypoxia. While acute increases in adenosine are important to counterbalance excessive inflammation or vascular leakage, chronically elevated adenosine levels may be toxic. Thus, we reasoned that clearance mechanisms might exist to offset deleterious influences of chronically elevated adenosine. Guided by microarray results revealing induction of endothelial adenosine deaminase (ADA) mRNA in hypoxia, we used in vitro and in vivo models of adenosine signaling, confirming induction of ADA protein and activity. Further studies in human endothelia revealed that ADA-complexing protein CD26 is coordinately induced by hypoxia, effectively localizing ADA activity at the endothelial cell surface. Moreover, ADA surface binding was effectively blocked with glycoprotein 120 (gp120) treatment, a protein known to specifically compete for ADA-CD26 binding. Functional studies of murine hypoxia revealed inhibition of ADA with deoxycoformycin (dCF) enhances protective responses mediated by adenosine (vascular leak and neutrophil accumulation). Analysis of plasma ADA activity in pediatric patients with chronic hypoxia undergoing cardiac surgery demonstrated a 4.1 ± 0.6-fold increase in plasma ADA activity compared with controls. Taken together, these results reveal induction of ADA as innate metabolic adaptation to chronically elevated adenosine levels during hypoxia. In contrast, during acute hypoxia associated with vascular leakage and excessive inflammation, ADA inhibition may serve as therapeutic strategy.
Identification and properties of proteases from an Acanthamoeba isolate capable of producing granulomatous encephalitis
Authors: Sissons James , Alsam Selwa , Goldsworthy Graham , Lightfoot Mary , Jarroll Edward L , Khan Naveed Ahmed
Published: May 2006

Background

Granulomatous amoebic encephalitis due to Acanthamoeba is often a fatal human disease. However, the pathogenesis and pathophysiology of Acanthamoeba encephalitis remain unclear. In this study, the role of extracellular Acanthamoeba proteases in central nervous system pathogenesis and pathophysiology was examined.

Results

Using an encephalitis isolate belonging to T1 genotype, we observed two major proteases with approximate molecular weights of 150 KD and 130 KD on SDS-PAGE gels using gelatin as substrate. The 130 KD protease was inhibited with phenylmethylsulfonyl fluoride (PMSF) suggesting that it is a serine protease, while the 150 KD protease was inhibited with 1, 10-phenanthroline suggesting that it is a metalloprotease. Both proteases exhibited maximal activity at neutral pH and over a range of temperatures, indicating their physiological relevance. These proteases degrade extracellular matrix (ECM), which provide structural and functional support to the brain tissue, as shown by the degradation of collagen I and III (major components of collagenous ECM), elastin (elastic fibrils of ECM), plasminogen (involved in proteolytic degradation of ECM), as well as casein and haemoglobin. The proteases were purified partially using ion-exchange chromatography and their effects were tested in an in vitro model of the blood-brain barrier using human brain microvascular endothelial cells (HBMEC). Neither the serine nor the metalloprotease exhibited HBMEC cytotoxicity. However, the serine protease exhibited HBMEC monolayer disruptions (trypsin-like) suggesting a role in blood-brain barrier perturbations.

Conclusion

Overall, these data suggest that Acanthamoeba proteases digest ECM, which may play crucial role(s) in invasion of the brain tissue by amoebae.
Acupuncture is a feasible treatment for post-thoracotomy pain: results of a prospective pilot trial
Authors: Vickers Andrew J , Rusch Valerie W , Malhotra Vivek T , Downey Robert J , Cassileth Barrie R
Published: May 2006

Background

Thoracotomy is associated with severe pain that may persist for years. Acupuncture is a complementary therapy with a proven role in pain control. A randomized trial showed that acupuncture was effective in controlling pain after abdominal surgery, but the efficacy of this technique for the treatment of thoracotomy pain has not been established. We developed a novel technique for convenient application of acupuncture to patients undergoing thoracotomy, and in a Phase II trial evaluated the safety of this intervention and the feasibility of doing a randomized trial.

Methods

Adult patients scheduled for unilateral thoracotomy with preoperative epidural catheter placement received acupuncture immediately prior to surgery. Eighteen semi-permanent intradermal needles were inserted on either side of the spine, and four were inserted in the legs and auricles. Needles were removed after four weeks. Using a numerical rating scale, pain was measured on the first five postoperative days. After discharge, pain was assessed using the Brief Pain Inventory at 7, 30, 60 and 90 days.

Results

Thirty-six patients were treated with acupuncture. Of these, 25, 23, and 22 patients provided data at 30, 60, and 90 days, respectively. The intervention was well tolerated by patients with only one minor and transient adverse event of skin ulceration.

Conclusion

The rate of data completion met our predefined criterion for determining a randomized trial to be feasible (at least 75% of patients tolerated the intervention and provided evaluable data). This novel intervention is acceptable to patients undergoing thoracotomy and does not interfere with standard preoperative care. There was no evidence of important adverse events. We are now testing the hypothesis that acupuncture significantly adds to standard perioperative pain management in a randomized trial.
Time trend and age-period-cohort effect on kidney cancer mortality in Europe, 1981–2000
Authors: Pérez-Farinós Napoleón , López-Abente Gonzalo , Pastor-Barriuso Roberto
Published: May 2006

Background

The incorporation of diagnostic and therapeutic improvements, as well as the different smoking patterns, may have had an influence on the observed variability in renal cancer mortality across Europe. This study examined time trends in kidney cancer mortality in fourteen European countries during the last two decades of the 20th century.

Methods

Kidney cancer deaths and population estimates for each country during the period 1981–2000 were drawn from the World Health Organization Mortality Database. Age- and period-adjusted mortality rates, as well as annual percentage changes in age-adjusted mortality rates, were calculated for each country and geographical region. Log-linear Poisson models were also fitted to study the effect of age, death period, and birth cohort on kidney cancer mortality rates within each country.

Results

For men, the overall standardized kidney cancer mortality rates in the eastern, western, and northern European countries were 20, 25, and 53% higher than those for the southern European countries, respectively. However, age-adjusted mortality rates showed a significant annual decrease of -0.7% in the north of Europe, a moderate rise of 0.7% in the west, and substantial increases of 1.4% in the south and 2.0% in the east. This trend was similar among women, but with lower mortality rates. Age-period-cohort models showed three different birth-cohort patterns for both men and women: a decrease in mortality trend for those generations born after 1920 in the Nordic countries, a similar but lagged decline for cohorts born after 1930 in western and southern European countries, and a continuous increase throughout all birth cohorts in eastern Europe. Similar but more heterogeneous regional patterns were observed for period effects.

Conclusion

Kidney cancer mortality trends in Europe showed a clear north-south pattern, with high rates on a downward trend in the north, intermediate rates on a more marked rising trend in the east than in the west, and low rates on an upward trend in the south. The downward pattern observed for cohorts born after 1920–1930 in northern, western, and southern regions suggests more favourable trends in coming years, in contrast to the eastern countries where birth-cohort pattern remains upward.
Assessing effects of a media campaign on HIV/AIDS awareness and prevention in Nigeria: results from the VISION Project
Authors: Keating Joseph , Meekers Dominique , Adewuyi Alfred
Published: May 2006

Background

In response to the growing HIV epidemic in Nigeria, the U.S. Agency for International Development (USAID) initiated the VISION Project, which aimed to increase use of family planning, child survival, and HIV/AIDS services. The VISION Project used a mass-media campaign that focused on reproductive health and HIV/AIDS prevention. This paper assesses to what extent program exposure translates into increased awareness and prevention of HIV/AIDS.

Methods

This analysis is based on data from the 2002 and 2004 Nigeria (Bauchi, Enugu, and Oyo) Family Planning and Reproductive Health Surveys, which were conducted among adults living in the VISION Project areas. To correct for endogeneity, two-stage logistic regression is used to investigate the effect of program exposure on 1) discussion of HIV/AIDS with a partner, 2) awareness that consistent condom use reduces HIV risk, and 3) condom use at last intercourse.

Results

Exposure to the VISION mass media campaign was high: 59%, 47%, and 24% were exposed to at least 1 VISION radio, printed advertisement, or TV program about reproductive health, respectively. The differences in outcome variables between 2002 baseline data and the 2004 follow-up data were small. However, those with high program exposure were almost one and a half (Odds Ratio [O.R.] = 1.47, 95% Confidence Interval [C.I.] 1.01–2.16) times more likely than those with no exposure to have discussed HIV/AIDS with a partner. Those with high program exposure were over twice (O.R. = 2.20, C.I. 1.49–3.25) as likely as those with low exposure to know that condom use can reduce risk of HIV infection. Program exposure had no effect on condom use at last sex.

Conclusion

The VISION Project reached a large portion of the population and exposure to mass media programs about reproductive health and HIV prevention topics can help increase HIV/AIDS awareness. Programs that target rural populations, females, and unmarried individuals, and disseminate information on where to obtain condoms, are needed to reduce barriers to condom use. Improvements in HIV/AIDS prevention behaviour are likely to require that these programmatic efforts be continued, scaled up, done in conjunction with other interventions, and targeted towards individuals with specific socio-demographic characteristics.
Activation of kinin B1 receptors induces chemotaxis of human neutrophils
Authors: Ehrenfeld P , Millan C , Matus C E , Figueroa J E , Burgos R A , Nualart F , Bhoola K D , Figueroa C D
Published: May 2006

Kinins are biologically active peptides that are powerful mediators of cellular inflammation. They mimic the cardinal signs of inflammation by inducing vasodilatation and by increasing vascular permeability and pain. Neutrophils are chemoattracted to sites of inflammation by several stimuli. However, the evidence concerning the chemotactic effect of kinin peptides has been contradictory. We analyzed the chemotactic effect of kinin B1 receptor agonists on neutrophils isolated from peripheral blood of human healthy subjects. Chemotaxis was performed using the migration under agarose technique. To test the effect of B1 receptor agonists, each assay was carried out overnight at 37°C in 5% CO2-95% air on neutrophils primed with 1 ng/ml interleukin-1β. Simultaneous experiments were performed using unprimed cells or cells challenged with formyl-Met-Leu-Phe (fMLP). A clear chemotactic activity was observed when primed neutrophils were challenged with Lys-des[Arg9]-bradykinin (LDBK) or des[Arg9]-bradykinin at 10−10 M but not when unprimed cells were used. A reduction in the chemotactic response was observed after priming of cells in the presence of 0.5 mM cycloheximide and 10 μg/ml brefeldin A, suggesting that some protein biosynthesis is required. Techniques such as reverse transcriptase-polymerase chain reaction and in situ hybridization confirmed the expression of the B1 receptor mRNA, and immunocytochemistry and autoradiography demonstrated the expression of the B1 receptor protein. In contrast to other chemoattractants such as fMLP, cytosolic intracellular calcium did not increase in response to the B1 receptor agonist LDBK. A generation of kinin B1 receptor agonists during the early phase of acute inflammation may favor the recruitment of neutrophils to the inflammatory site.
What I would say to a patient who asked me about this article
Authors: Scott Allan
Published: May 2006

Electroconvulsive therapy (ECT) remains an important treatment option for severe depressive illness, but it can have side-effects, including permanent gaps in memory. Where minimising the intellectual side-effects of treatment has priority, then treatment to only one side of the head (unilateral ECT) is preferable; where the speed of clinical improvement is paramount, then bilateral ECT may be preferred. The choice of how ECT is administered should, where possible, be part of the process of informed consent.
Comparison of the Dexamethasone-Suppressed Corticotropin-Releasing Hormone Test and Low-Dose Dexamethasone Suppression Test in the Diagnosis of Cushing’s Syndrome
Authors: Martin N. M. , Dhillo W. S. , Banerjee A. , Abdulali A. , Jayasena C. N. , Donaldson M. , Todd J. F. , Meeran K.
Published: May 2006

Context: The low-dose dexamethasone suppression test (LDDST) is widely used in confirming a diagnosis of Cushing’s syndrome. CRH administration at the end of an LDDST has been reported to improve the diagnostic accuracy of this test.

Objective: Our objective was to assess whether CRH administration after a standard LDDST (LDDST-CRH test) improves diagnostic accuracy in Cushing’s syndrome.

Design, Setting, and Participants: Thirty-six individuals with a clinical suspicion of Cushing’s syndrome each completed a standard LDDST and an LDDST-CRH test at Hammersmith Hospitals NHS Trust, London. The LDDST involved administration of 0.5 mg oral dexamethasone given 6-hourly for 48 h. Serum cortisol was measured 6 h after the last dose of dexamethasone, with a value of 50 nmol/liter or below excluding Cushing’s syndrome. Immediately after this, the LDDST-CRH test commenced with administration of a ninth dose of 0.5 mg dexamethasone. Exactly 2 h later, 100 μg human-sequence CRH was administered. Serum cortisol was measured 15 min after the CRH injection, with a value of less than 38 nmol/liter also excluding Cushing’s syndrome.

Main Outcome Measure: Diagnosis or exclusion of Cushing’s syndrome was the main outcome measure.

Results: Twelve subjects were diagnosed with Cushing’s syndrome (eight Cushing’s disease and four primary adrenal). The sensitivity of the LDDST in diagnosing Cushing’s syndrome was 100%, with a specificity of 88%. In contrast, although the sensitivity of the LDDST-CRH test was also 100%, specificity was reduced at 67%. These results give a positive predictive value of 80% for the LDDST and 60% for the LDDST-CRH test.

Conclusion: This small study suggests that the addition of CRH to the LDDST does not improve the diagnostic accuracy of the standard LDDST in Cushing’s syndrome.
Color discrimination in the red range with only one long-wavelength sensitive opsin
Authors: Zaccardi Guillermo , Kelber Almut , Sison-Mangus Marilou P. , Briscoe Adriana D.
Published: May 2006

The basic precondition for color vision is the presence of at least two receptor types with different spectral sensitivities. The sensitivity of a receptor is mostly defined by the opsin-based visual pigment expressed in it. We show here, through behavioral experiments, that the nymphalid butterfly Heliconius erato, although it expresses short and medium wavelength opsins and only one long wavelength opsin, discriminates colors in the long-wavelength range (590 nm, 620 nm and 640 nm), whereas another nymphalid, Vanessa atalanta, despite having color vision, is unable to do so. In the eyes of H. erato we identified filtering pigments very close to the rhabdom which differ between ommatidia and produce the yellow and red ommatidial reflection seen under orthodromic illumination. The eyes of V. atalanta lack the filtering pigments, and reflect a homogeneous orange. We hypothesize that the filtering pigments found in the eyes of H. erato may shift the spectral sensitivity peak of the long wavelength receptors in some ommatidia towards longer wavelengths. The comparison of the signals between the two new receptor types makes color discrimination in the red range possible. To our knowledge, this is the first behavioral proof of color vision based on receptors expressing the same opsin.
Enzymatic Peptide Synthesis by the Coupling of (Z)-α-Dehydroglutamate with L-α-Amino Acids Using Papain
Authors: Shin Chung-gi , Takahashi Nobuyuki
Published: May 2006

Enzymatic coupling of N-protected α,γ-dimethyl α-dehydroglutamate with L-α-leucine amide using papain at pH 8.0 was first achieved to give α-dehydroglutamylleucine derivatives.
Oxidative Cleavage of Olefins into Carboxylic Acids with Hydrogen Peroxide by Tungstic Acid
Authors: Oguchi Takahito , Ura Toshikazu , Ishii Yasutaka , Ogawa Masaya
Published: May 2006

A facile conversion of olefins into carboxylic acids could be achieved by using aqueous hydrogen peroxide (35%-H2O2) in the presence of catalytic amounts of tungstic acid (5 wt%). The oxidation was markedly influenced by the acidity of the reaction medium, and it was found to proceed favorably under a weak acidic condition (pH 4–5).
Photo-induced Intramolecular Electron Transfer of Viologen with Hexacyanoferrate(II) Ion
Authors: Nanasawa Masato , Kaneko Makoto , Kamogawa Hiroyoshi
Published: May 2006

The charge-transfer band of 1,1′-diamyl-4,4′-bipyridinium hexacyanoferrate(II) varied by the kind of solvent and its absorption was enhanced by photo-induced intramolecular electron transfer via radical-ion complex.
Preparation and Electrochemical Response of Poly(4-vinylpyridine)-Coordinated Oxo-acetato Triruthenium Cluster Film
Authors: Akashi Daisuke , Kido Hiroaki , Sasaki Yoichi , Ito Tasuku
Published: May 2006

The trinuclear ruthenium cluster [RuIII3(μ3-O)(μ-CH3COO)6(pyridine)2(CH3OH)]+ was incorporated into poly(4-vinylpyridine) through substitution of the pyridyl residue for CH3OH to form a new macromolecular complex, which showed distinctive reversible cyclic voltammographic waves at −0.05 and +0.95 V vs. SCE in aqueous CF3COO− medium at pH 3, when coated on a glassy carbon electrode as a transparent film.
(μ-Alkoxo)diiron(II,II) Complexes of N,N,N′,N′-Tetrakis(2-(6-methylpyridyl)methyl)-1,3-diaminopropane-2-olate and the Reversible Formation of the O2-Adducts
Authors: Hayashi Yoshihito , Suzuki Masatatsu , Uehara Akira , Mizutani Yasuhisa , Kitagawa Teizo
Published: May 2006

(μ-Alkoxo)(μ-carboxylato)diiron(II,II) complexes with hindered dinucleating ligand were synthesized and the structure of μ-benzoato derivative was determined by X-ray analysis. The complexes showed reversible oxygenation in acetonitrile and dichloromethane. Resonance Raman spectra of these species demonstrated a possibility of unsymmetrical μ-η1-η1′ binding of the oxygen toward the diiron centers.
Development and Photovoltaic Performance of Oligothiophene-sensitized TiO2 Solar Cells
Authors: Tanaka Koki , Takimiya Kazuo , Otsubo Tetsuo , Kawabuchi Koji , Kajihara Shotaro , Harima Yutaka
Published: May 2006

Novel dye-sensitized TiO2 solar cells have been developed using a variety of oligothiophenecarboxylic acids. These cells showed relatively high photovoltaic performances (η = 0.41–1.29%), which are largely dependent on the chain lengths of the oligothiophenes and the number of the carboxylic groups.
Montelukast Treatment of Urticaria
Authors: McBayne Tyrone O , Siddall O'Rita M
Published: May 2006

Objective:

To review clinical trial data to determine the benefits of using montelukast alone or as combination therapy in the treatment of urticaria.

Data Sources:

MEDLINE (1966–March 2006) and International Pharmaceutical Abstracts (1970–October 2005) were searched to find clinical trial publications that addressed the use of montelukast in urticaria.

Data Synthesis:

Six clinical trials were identified. Montelukast was compared alone and as combination therapy with nonsedating histamine1-receptor antagonists to determine efficacy and safety. Patients had chronic or physical urticaria. The results were mixed. Some studies demonstrated that montelukast can decrease urticarial symptoms with minimal adverse effects, while others found no differences.

Conclusion:

Large-scale, controlled trials are needed to determine which patients would likely benefit from treatment with montelukast.
Estimation of Creatinine Clearance in End-Stage Liver Disease
Authors: Nix David E , Erstad Brian L , Nakazato Paul Z , Barletta Jeffrey F , Matthias Kathryn R , Krueger Todd S
Published: May 2006

Background:

Estimation of renal function in patients with end-stage liver disease (ESLD) is complicated by several factors.

Objective:

To develop a practical and relatively inexpensive method for estimating creatinine production and clearance in patients with ESLD.

Methods:

Serum creatinine concentrations and urinary excretion of creatinine were measured in 27 patients with moderate-to-severe liver disease with the goal of developing equations to predict creatinine clearance from serum creatinine. Subjects were studied during an initial evaluation for a liver transplant program. Two 24 hour urine specimens were collected along with 3 serum samples over a 2 day evaluation period. Serum and urine creatinine concentrations were determined using both a modified Jaffé (autoanalyzer) method and an HPLC method. The data were analyzed using nonlinear mixed-effects modeling.

Results:

Considering both statistical criteria and physiological conventions through allometric scaling theory, creatinine clearance (mL/min) in males can be estimated as (80/serum creatinine) × (actual body weight/70)0.75. For females, the same equation is valid, but the result is multiplied by 0.661. A simplified equation without the exponent is presented, along with equations that are appropriate when an HPLC assay is used for greater specificity.

Conclusions:

These equations offer potential for improved estimation of creatinine clearance in patients with liver impairment; however, they need further validation using an independent group of subjects.
Canine Indolent Nodular Lymphoma
Authors: Valli V. E. , Vernau W. , de Lorimier L.-P. , Graham P. S. , Moore P. F.
Published: May 2006

Sixty-six cases of indolent canine lymphoid proliferation were reviewed. Age ranged from 1.5 to 16 years (median 9.0 years). Dogs of 26 breeds, plus 13 of mixed breeding or unknown lineage, were represented. B-Cell lymphomas (CD79a+) predominated. Marginal zone lymphoma (MZL), the largest group, involved lymph node (33 cases) and spleen (13 cases), with both tissues involved in five of these cases. Follicular lymphoma (FL) involved lymph nodes (five cases), and mantle cell lymphoma (MCL) occurred as solitary splenic masses (three cases). Nodal CD3+ T-zone lymphomas (TZL) (10 cases), were included since they resembled late-stage MZL at the architectural level. Two cases of marginal zone hyperplasia (MZH) were included to aid in differentiation of early MZL. Clonality status was determined in 54 cases by analysis of immunoglobulin heavy chain (IGH) and T-cell antigen receptor gamma (TCRG) gene rearrangement. Clonal rearrangement of IGH was detected in 28 of 35 MZL cases (80%), four of four FL cases (100%) and three of three MCL cases (100%). Concurrent cross lineage rearrangement of TCRG was detected in six MZL and two FL cases. Clonal rearrangement of TCRG was documented in five of eight TZL cases (63%). Limited survival data obtained for 18 dogs indicated that the B-cell lymphomas (MZL, MCL, and FL) and the T-cell lymphoma (TZL) were associated with indolent behavior and long survival. Although to the authors' knowledge, the true incidence of canine indolent lymphomas is unknown, the tumors are not rare and may have been underrecognized. Recognition of their architectural features, routine application of immunophenotyping, and molecular clonality assessment should alleviate this.
Cerebellar Hypoplasia Associated with an Avian Leukosis Virus Inducing Fowl Glioma
Authors: Toyoda T. , Ochiai K. , Hatai H. , Murakami M. , Ono E. , Kimura T. , Umemura T.
Published: May 2006

Fowl glioma-inducing virus (FGV), which belongs to subgroup A of avian leukosis virus (ALV), shows tumorigenicity and pathogenicity, mainly in the nervous system, and causes astrocytoma and perineurioma. Apart from these neoplasms, cerebellar anomaly was found in chickens infected with FGV in ovo. The study reported here describes the morphologic characteristics of the affected cerebellum. Specific-pathogen-free chickens (C/O) were inoculated with FGV through the yolk sac on the 7th day of incubation. The cerebellar anomaly included diffuse depletion of granular cells of the internal granular layer (IGL), remnants of the external granular layer (EGL), and disorganization of the Purkinje cell layer. These cerebellar changes were observed in all birds except one. in the infected embryos, the EGL was thicker and had an irregular arrangement with a thin molecular layer (ML) and IGL, compared with the control. The granular cells were immunohistochemically positive for ALV common antigen. immunohistochemical analysis for vimentin revealed disarrangement and decreased number of Bergmann's fibers. Use of the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method and electron microscopy indicated that apoptotic granular cells were frequently observed in the EGL and ML. These results suggested that the cerebellar anomaly was hypoplasia, principally resulting from the apoptosis of granular cells in the EGL and ML caused by FGV infection and that the cell loss induced obstruction of granular cell migration and disarrangement of Bergmann's fibers in the ML.
Massive Mortality of Common Carp (Cyprinus carpio carpio) in the St. Lawrence River in 2001: Diagnostic Investigation and Experimental Induction of Lymphocytic Encephalitis
Authors: Monette S. , Dallaire A. D. , Mingelbier M. , Groman D. , Uhland C. , Richard J.-P. , Paillard G. , Johannson L. M. , Chivers D. P. , Ferguson H. W. , Leighton F. A. , Simko E.
Published: May 2006

A massive fish kill affecting exclusively common carp ( Cyprinus carpio carpio) in the St. Lawrence River, Québec, Canada, during the summer of 2001 was investigated by use of laboratory diagnostic methods and by an attempt to experimentally induce the disease. The ultimate causes of mortality were opportunistic bacterial infections with Aeromonas hydrophila and Flavobacterium sp. secondary to immunosuppression induced by physiologic (i.e., spawning) and environmental (i.e., high temperatures and low water levels) stressors, and possibly enhanced by an infection causing lymphocytic encephalitis observed in 9 of 18 (50%) fish examined. Experimental induction of disease was attempted in captured wild carp by administration of crude and filtered (particulate <0.22 μm) inocula prepared from a homogenate of tissues from carp affected by the natural outbreak. Although significant clinical disease or mortality was not induced by experimental challenge, lymphocytic encephalitis similar to the one observed in naturally affected carp was induced in four of seven (57%) fish administered crude inoculum and four of seven (57%) fish administered filtered inoculum. None of the control fish inoculated with sterile phosphate-buffered saline ( n = 6) were affected by encephalitis. The cause of the encephalitis observed in carp from the natural outbreak and in experimentally inoculated fish could not be determined by use of virus isolation and transmission electron microscopy.
Multiple Endocrine Neoplasia Type-I-like Syndrome in Two Cats
Authors: Roccabianca P. , Rondena M. , Paltrinieri S. , Pocacqua V. , Scarpa P. , Faverzani S. , Scanziani E. , Caniatti M.
Published: May 2006

Multiple endocrine neoplasia (MEN) embodies a group of diseases in human patients and domestic animals that are characterized by hyperplasia or neoplasia, or both, of two or more endocrine tissues. The MEN-1 syndrome is associated with menin gene mutations that induce various combinations of parathyroid, pituitary, and pancreatic endocrine tumors in humans. Two male, Domestic Shorthair cats developed symmetric alopecia, insulin-resistant diabetes mellitus, and pituitary-dependent hyperadrenocorticism at 12 and 13 years of age. Examination of skin biopsy specimens revealed atrophic dermatosis associated with hyperadrenocorticism. In one cat, cutaneous lesions consistent with paraneoplastic alopecia associated with pancreatic adenocarcinoma also were evident. Multiple invasive pancreatic beta cell carcinomas, pituitary corticotroph adenomas, and thyroid C-cell and parathyroid chief cell hyperplasia were diagnosed on the basis of results of gross, histologic, and immunohistochemical findings in both cats. Pancreatic exocrine adenocarcinoma was diagnosed in both cats. one cat also had hepatocellular carcinoma. Exons 1-8 of the feline menin gene were sequenced and were found to bear 93% homology with the human gene sequence, and the corresponding amino acid sequences shared 98% homology. Purification of total RNA and amplification of cDNA from lesional tissues to document mutations in the feline menin gene sequence were unsuccessful. The combination of lesions observed was consistent with the diagnosis of MEN-1-like syndrome in both cats.
Sudden Death Associated with Clostridium sordellii in Captive Lions (Panthera leo)
Authors: de la Fe C. , Rodríguez J. M. , Ramírez G. A. , Hervás J. , Gil J. , Poveda J. B.
Published: May 2006

In the spring of 2003, a series of sudden deaths in a group of adult lions ( Panthera leo) with a previous history of depression, inanition, and lethargy, was investigated. Five animals died within 24 to 36 hours after onset of signs of disease. Serologic screening for viral disease detection was negative, evidence of parasites was not detected, and results of a complete blood count and serum biochemical analysis were within reference intervals in all lions. The most relevant lesions observed were multiple areas of necrosis and hemorrhage in the intestinal outer muscular layer, and cellulitis with an intense bloody edema in the mesenteric and the pericardial fat tissue. On the basis of the fulminant course of the disease, the gross and histologic findings, and the isolation and identification of Clostridium sordellii, a diagnosis of infectious myositis and cellulitis associated with acute clostridiosis was made. To the authors' knowledge, this is the first report of sudden death associated with C. sordellii in felines.
Listeric Meningoencephalomyelitis in a Cougar (Felis concolor): Characterization by Histopathologic, Immunohistochemical, and Molecular Methods
Authors: Langohr I. M. , Ramos-Vara J. A. , Wu C. C. , Froderman S. F.
Published: May 2006

Listeria monocytogenes has been recognized as an important food-borne pathogen in animals. Records of the disease caused by this bacterium in large felids are, however, rare. The nervous form of listeriosis was diagnosed in a 12-year-old male cougar ( Felis concolor) with a several-day history of neurologic disease characterized by excess salivation, head pressing, and circling that progressed to recumbency and death. Microscopically, the main alteration in the brain and spinal cord was a variably severe meningoencephalomyelitis composed mainly of mononuclear cell aggregates with fewer neutrophils. L. monocytogenes was isolated from the brain by microbiological culture, and L. monocytogenes antigen was detected in formalin-fixed, paraffin-embedded sections of brain and spinal cord by immunohistochemical analysis. On the basis of the nucleotide sequence of the 16S rRNA gene, the isolated strain was determined to be serotype 1/2a. Food-borne transmission of the bacterium was suspected, but food was not available for testing.
Multicentric Physeal Dysplasia in Two Cats
Authors: Newton A. L. , Craig L. E.
Published: May 2006

Feline physeal dysplasia typically presents as unilateral or bilateral, atraumatic, slipped capital femoral epiphysis. The femoral physeal lesion consists of retention of a cartilaginous physis beyond the expected age of closure, with disorganization of the chondrocytes and subsequent slippage. in this article, we describe two cats with feline physeal dysplasia and slipped capital femoral epiphysis that died of unrelated causes (cardiomyopathy and lymphosarcoma). At necropsy, additional sites were found to have retained physes with similar abnormal arrangement of chondrocytes. This confirms that physeal dysplasia in cats is a widespread multicentric disorder of chondrocytes that precedes the development of slipped capital femoral epiphysis.
Abelian extensions of semisimple graded CR algebras
Authors: Altomani Andrea , Nacinovich Mauro
Published: May 2006

In this paper we take up the problem of describing the CR vector bundles M over compact standard CR manifolds S, which are themselves standard CR manifolds. They are associated to special graded Abelian extensions of semisimple graded CR algebras.
LP-orientations of cubes and crosspolytopes
Authors: Develin Mike
Published: May 2006

In a paper presented at a 1996 conference, Holt and Klee introduced a set of necessary conditions for an orientation of the graph of a d-polytope to be induced by a realization into ℝ
n
and a linear function on that space. In general, it is an open question to decide whether for a polytope P every orientation of its graph satisfying these conditions can in fact be realized in this fashion; two natural families of polytopes to consider are cubes and crosspolytopes. For cubes, we show that, as n grows, the percentage of n-cube Holt–Klee orientations which can be realized goes asymptotically to 0. For crosspolytopes, we give a stronger set of conditions which are both necessary and sufficient for an orientation to be in this class; as a corollary, we prove that all shellings of cubes are line shellings.
“One of the last vestiges of gender bias”: The characterization of women through the telling of dirty jokes in Ally McBeal
Authors: Bubel Claudia M , Spitz Alice
Published: May 2006

Based on an audience-centered model of television discourse, we show that verbal interaction is one of the principal means of characterization in film. One of the linguistic phenomena screenwriters exploit and manipulate to develop their characters is verbal humor. For instance, the ways in which interactants on screen produce and respond to jokes is critical in their characterization. We look at an episode of the US American sitcom Ally McBeal, in which two women tell dirty jokes. We show that although the structure of both jokes as well as their respective performance equally meet the demands of good (tellings of) jokes, the screenplay is constructed in such a way that one of them fails to elicit laughter. This is achieved through creating expectations in the viewer prior to the telling of the jokes and through having the women frame their jokes dierently. This research has implications for the study of both gender and humor in conversation, for even though we look at constructed dialogue, it yields insight into underlying knowledge about real conversation.
Oxidative Stress and Mitogen-Activated Protein Kinase Phosphorylation Mediate Ammonia-Induced Cell Swelling and Glutamate Uptake Inhibition in Cultured Astrocytes
Authors: Jayakumar A. R. , Panickar K. S. , Murthy Ch. R. K. , Norenberg M. D.
Published: May 2006

Hepatic encephalopathy (HE) is a major neurological complication in patients with severe liver failure. Elevated levels of ammonia have been strongly implicated as a factor in HE, and astrocytes appear to be the primary target of its neurotoxicity. Mechanisms mediating key aspects of ammonia-induced astrocyte dysfunction such as cell swelling and inhibition of glutamate uptake are not clear. We demonstrated previously that cultured astrocytes exposed to ammonia increase free radical production. We now show that treatment with antioxidants significantly prevents ammonia-induced astrocyte swelling as well as glutamate uptake inhibition. Because one consequence of oxidative stress is the phosphorylation of mitogen-activated protein kinases (MAPKs), we investigated whether phosphorylation of MAPKs may mediate astrocyte dysfunction. Primary cultured astrocytes exposed to 5 mmNH4Cl for different time periods (1–72 h) significantly increased phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38MAPK, and c-Jun N-terminal kinase (JNK) 1/2/3, which was inhibited by appropriate MAPK inhibitors 1, 4-diamino-2, 3-dicyano-1, 4-bis (2-aminophenylthio) butadiene (UO126; for ERK1/2),trans-1-(4-hydroxyclyclohexyl)-4-(4-fluorophenyl)-5-(2-methoxypyrimidin-4-yl)imidazole (SB 239063; for p38MAPK), and anthra[1,9-cd]pyrazol-6(2H)-one (SP600125; for JNK1/2/3), as well as by antioxidants. Kinase inhibitors partially or completely prevented astrocyte swelling. Although SB239063 and SP600125 significantly reversed glutamate uptake inhibition and ammonia-induced decline in glutamate-aspartate transporter protein levels, UO126 did not, indicating a differential effect of these kinases in ammonia-induced astrocyte swelling and glutamate transport impairment. These studies strongly suggest the involvement of oxidative stress and phosphorylation of MAPKs in the mechanism of ammonia-induced astrocyte dysfunction associated with ammonia neurotoxicity.
Short Amyloid-β (Aβ) Immunogens Reduce Cerebral Aβ Load and Learning Deficits in an Alzheimer's Disease Mouse Model in the Absence of an Aβ-Specific Cellular Immune Response
Authors: Maier Marcel , Seabrook Timothy J. , Lazo Noel D. , Jiang Liying , Das Pritam , Janus Christopher , Lemere Cynthia A.
Published: May 2006

Amyloid-β (Aβ) immunotherapy lowers cerebral Aβ and improves cognition in mouse models of Alzheimer's disease (AD). A clinical trial using active immunization with Aβ1–42 was suspended after ∼6% of patients developed meningoencephalitis, possibly because of a T-cell reaction against Aβ. Nevertheless, beneficial effects were reported in antibody responders. Consequently, alternatives are required for a safer vaccine. The Aβ1–15 sequence contains the antibody epitope(s) but lacks the T-cell reactive sites of full-length Aβ1–42. Therefore, we tested four alternative peptide immunogens encompassing either a tandem repeat of two lysine-linked Aβ1–15 sequences (2×Aβ1–15) or the Aβ1–15 sequence synthesized to a cross-species active T1 T-helper-cell epitope (T1-Aβ1–15) and each with the addition of a three-amino-acid RGD (Arg-Gly-Asp) motif (R-2×Aβ1–15; T1-R-Aβ1–15). High anti-Aβ antibody titers were observed in wild-type mice after intranasal immunization with R-2×Aβ1–15 or 2×Aβ1–15 plus mutantEscherichia coliheat-labile enterotoxin LT(R192G) adjuvant. Moderate antibody levels were induced after immunization with T1-R-Aβ1–15 or T1-Aβ1–15 plus LT(R192G). Restimulation of splenocytes with the corresponding immunogens resulted in moderate proliferative responses, whereas proliferation was absent after restimulation with full-length Aβ or Aβ1–15. Immunization of human amyloid precursor protein, familial AD (hAPPFAD) mice with R-2×Aβ1–15 or 2×Aβ1–15 resulted in high anti-Aβ titers of noninflammatory T-helper 2 isotypes (IgG1 and IgG2b), a lack of splenocyte proliferation against full-length Aβ, significantly reduced Aβ plaque load, and lower cerebral Aβ levels. In addition, 2×Aβ1–15-immunized hAPPFADanimals showed improved acquisition of memory compared with vehicle controls in a reference-memory Morris water-maze behavior test that approximately correlated with anti-Aβ titers. Thus, our novel immunogens show promise for future AD vaccines.
Dynamics of Hippocampal and Cortical Activation during Consolidation of a Nonspatial Memory
Authors: Ross Robert S. , Eichenbaum Howard
Published: May 2006

Observations of temporally graded retrograde amnesia after hippocampal damage suggest that the hippocampal region plays a critical, time-limited role in memory consolidation. However, these observations do not indicate where permanent memory is stored, nor do they clarify whether the hippocampus normally remains involved in a nonessential way. Evidence from multiple neural imaging studies indicate the time-limited role of the hippocampus and suggest that the anterior cingulate cortex is a critical storage site of different types of long-term memory. However, each of the previous studies examined spatial memory, leaving open the question of whether different cortical areas support long-term memory for other types of material. We characterized the course of involvement of cortical and hippocampal areas in animals trained in an explicitly nonspatial task. First, we confirmed previous findings that hippocampal damage produces temporally graded retrograde amnesia for the social transmission of a food preference (STFP) within our experimental protocol. Damage to the hippocampal region 1 d, but not 21 d, after training impaired subsequent recall of STFP. Then, we characterized the anatomical patterns of activation of the immediate early gene c-fosduring retrieval of STFP immediately and 1, 2, and 21 d after training. The ventral subiculum was activated during retrieval shortly after learning, but the level of activation declined at successive times. In contrast, olfactory recipient regions including piriform, entorhinal, and orbitofrontal cortex showed the opposite pattern, increasingly greater activation in successively later retrieval tests. These findings support the view that different cortical networks support long-term memory for different types of information.
ARF6 and EFA6A Regulate the Development and Maintenance of Dendritic Spines
Authors: Choi Seungwon , Ko Jaewon , Lee Jae-Ran , Lee Hyun Woo , Kim Karam , Chung Hye Sun , Kim Hyun , Kim Eunjoon
Published: May 2006

The cellular and molecular mechanisms underlying the development and maintenance of dendritic spines are not fully understood. ADP-ribosylation factor 6 (ARF6) is a small GTPase known to regulate actin remodeling and membrane traffic. Here, we report involvement of ARF6 and exchange factor for ARF6 (EFA6A) in the regulation of spine development and maintenance. An active form of ARF6 promotes the formation of dendritic spines at the expense of filopodia. EFA6A promotes spine formation in an ARF6 activation-dependent manner. Knockdown of ARF6 and EFA6A by small interfering RNA decreases spine formation. Live imaging indicates that ARF6 knockdown decreases the conversion of filopodia to spines and the stability of early spines. The spine-promoting effect of ARF6 is partially blocked by Rac1. ARF6 and EFA6A protect mature spines from inactivity-induced destabilization. These results suggest that ARF6 and EFA6A may regulate the conversion of filopodia to spines and the stability of both early and mature spines.
Regulation of Nuclear Factor κB in the Hippocampus by Group I Metabotropic Glutamate Receptors
Authors: O’Riordan Kenneth J. , Huang I-Chia , Pizzi Marina , Spano PierFranco , Boroni Flora , Egli Regula , Desai Priyanka , Fitch Olivia , Malone Lauren , Jin Ahn Hyung , Liou Hsiou-Chi , Sweatt J. David , Levenson Jonathan M.
Published: May 2006

An increasing amount of evidence suggests that the family of nuclear factor κB (NF-κB) transcription factors plays an important role in synaptic plasticity and long-term memory formation. The present study investigated the regulation of NF-κB family members p50, p65/RelA, and c-Rel in the hippocampus in response to metabotropic glutamate receptor (mGluR) signaling. Activation of group I metabotropic glutamate receptors (GpI-mGluRs) with the agonist (S)-3,5-dihydroxyphenylglycine (DHPG) resulted in a time-dependent increase in DNA binding activity of p50, p65, and c-Rel in area CA1 of the hippocampus. An antagonist of mGluR5, 2-Methyl-6-(phenylethynyl)pyridine, inhibited the DHPG-induced activation of NF-κB, whereas an antagonist of mGluR1, (S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid, did not. Using a series of inhibitors, we investigated the signaling pathways necessary for DHPG-induced activation of NF-κB and found that they included the phosphatidyl inositol 3-kinase, protein kinase C, mitogen-activated protein kinase kinase, and p38-mitogen-activated protein kinase pathways. To determine the functional significance of mGluR-induced regulation of NF-κB, we measured long-term depression (LTD) of Schaffer-collateral synapses in the hippocampus of c-Rel knock-out mice. Early phase LTD was normal in c-rel−/−mice. However, late-phase LTD (>90 min) was impaired in c-rel−/−mice. The observations of this deficit in hippocampal synaptic plasticity prompted us to further investigate long-term memory formation in c-rel−/−mice. c-rel−/−mice exhibited impaired performance in a long-term passive avoidance task, providing additional evidence for c-Rel in long-term memory formation. These results demonstrate that the NF-κB transcription factor family is regulated by GpI-mGluRs in the hippocampus and that the c-Rel transcription factor is necessary for long-term maintenance of LTD and formation of long-term memory.
Involvement of Protein Synthesis and Degradation in Long-Term Potentiation of Schaffer Collateral CA1 Synapses
Authors: Karpova Anna , Mikhaylova Marina , Thomas Ulrich , Knöpfel Thomas , Behnisch Thomas
Published: May 2006

Expression of synaptic plasticity involves the translation of mRNA into protein and, probably, active protein degradation via the proteasome pathway. Here, we report on the rapid activation of synthesis and degradation of a probe protein with the induction of long-term potentiation (LTP) in the hippocampal Schaffer collateral CA1 pathway. The proteasome inhibitor MG132 significantly reduced the field EPSP slope potentiation and LTP maintenance without acutely affecting basal synaptic transmission. To visualize protein dynamics, CA1 pyramidal cells of hippocampal slices were transfected with Semliki Forest virus particles expressing a recombinant RNA. This RNA contained the coding sequence for a degradable green fluorescence protein with a nuclear localization signal (NLS-d1EGFP) followed by a 3′- untranslated region dendritic targeting sequence. NLS-d1EGFP fluorescence remained stable in the low-frequency test stimulation but increased with LTP induction in the cell body and in most dendritic compartments of CA1 neurons. Applying anisomycin, a protein synthesis inhibitor, caused NLS-d1EGFP levels to decline; a proteasome inhibitor MG132 reversed this effect. In the presence of anisomycin, LTP induction accelerated the degradation of NLS-d1EGFP. When both inhibitors were present, NLS-d1EGFP levels remained unaffected by LTP induction. Moreover, LTP-induced acceleration of NLS-d1EGFP synthesis was blocked by rapamycin, which is consistent with the involvement of dendritic mammalian target of rapamycin in LTP-triggered translational activity.

Our results clearly demonstrate that LTP induction not only leads to a rapid increase in the rate of protein synthesis but also accelerates protein degradation via the proteasome system.