Plasticity of orientation preference maps in the visual cortex of adult cats

In contrast to the high degree of experience-dependent plasticity usually exhibited by cortical representational maps, a number of experiments performed in visual cortex suggest that the basic layout of orientation preference maps is only barely susceptible to activity-dependent modifications. In fact, most of what we know about activity-dependent plasticity in adults comes from experiments in somatosensory, auditory, or motor cortex. Applying a stimulation protocol that has been proven highly effective in other cortical areas, we demonstrate here that enforced synchronous cortical activity induces major changes of orientation preference maps (OPMs) in adult cats. Combining optical imaging of intrinsic signals and electrophysiological single-cell recordings, we show that a few hours of intracortical microstimulation (ICMS) lead to an enlargement of the cortical representational zone at the ICMS site and an extensive restructuring of the entire OPM layout up to several millimeters away, paralleled by dramatic changes of pinwheel numbers and locations. At the single-cell level, we found that the preferred orientation was shifted toward the orientation of the ICMS site over a region of up to 4 mm. Our results show that manipulating the synchronicity of cortical activity locally without invoking training, attention, or reinforcement, OPMs undergo large-scale reorganization reminiscent of plastic changes observed for nonvisual cortical maps. However, changes were much more widespread and enduring. Such large-scale restructuring of the visual cortical networks indicates a substantial capability for activity-dependent plasticity of adult visual cortex and may provide the basis for cognitive learning processes.     

Effect of sex on Coxiella burnetii infection: protective role of 17beta-estradiol

Q fever is a zoonosis caused by Coxiella burnetii and recently has been recognized as a potential agent of bioterrorism. In Q fever, men are symptomatic more often than women, despite equal seroprevalence. We hypothesized that sex hormones play a role in the pathogenesis of C. burnetii infection. When C57/BL6 mice were injected with C. burnetii, bacteria load and granuloma numbers were lower in females than in males. Ovarectomized mice showed increased bacteria load in the spleen and the liver, similar to that found in males. The granuloma number was also increased in ovarectomized mice and reached the levels found in males. Tissue infection and granulomatous response are largely under the control of estrogens: treatment of ovarectomized mice with 17beta-estradiol reduced both bacteria loads and granuloma numbers. These results show that sex hormones control host response to C. burnetii infection and may account for host-dependent clinical presentation of Q fever.     

Androgens exert selective effects on protein kinase C induced LH and FSH release in rat anterior pituitary cells in culture

This study compares the selective effect of androgens on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release induced either by LH-releasing hormone (LH-RH) or by protein kinase C activation in rat anterior pituitary cells in culture. In control cells, phorbol-12-myristate-13-acetate (PMA) stimulated the release of radioimmunoassayable LH and FSH in a dose-dependent manner at an ED50 value of 5.95 +/- 1.45 nM. The maximal release of gonadotropins induced during a 3-hour incubation with PMA was 40-60% of that induced by LH-RH. Preincubation of the cells for 2-4 days with 10 nM 5 alpha-dihydrotestosterone (DHT) decreased by approximately 60% the subsequent release of LH induced by 100 nM LH-RH or by 500 nM PMA during a subsequent 3-hour incubation. The inhibitory effect of DHT was completely suppressed by coincubation with the antiandrogen hydroxyflutamide. DHT exerted a similar inhibitory effect on LH release induced by another stimulator of protein kinase C activity, namely 1-oleoyl-2-acetylglycerol. The potent inhibitory action of DHT on LH-RH- or PMA-induced LH release was exerted at an ED50 value of approximately 10 pM. Contrary to the effect on LH, the FSH response to LH-RH or to PMA was increased by preincubation with 2 nM DHT, the stimulatory effect of the androgen being completely antagonized by hydroxyflutamide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cellular localization of the target structures recognized by the anti-Jo-1 antibody: immunofluorescence studies on cultured human myoblasts

Antibodies to Jo-1 (alpha Jo-1) are most characteristically detected in patients with the idiopathic inflammatory muscle disease polymyositis (PM). The Jo-1 antigen has previously been identified as histidyl-tRNA synthetase (HRS). In order to clarify the cellular localization of the antigenic targets recognized by the alpha Jo-1 antibody, immunofluorescence (IF) studies were performed with cultured human myoblasts. Incubation with alpha Jo-1 positive sera demonstrated granular cytoplasmic as well as nuclear staining, but only the cytoplasmic fluorescence was specifically inhibited by preabsorbing the sera with recombinant histidyl-tRNA synthetase (rHRS). A polyclonal rabbit anti-rHRS sera demonstrated granular cytoplasmic IF which was also specifically inhibited by preincubation with rHRS protein. Alpha Jo-1 negative healthy control or patient sera demonstrated nonspecific low intensity staining. 35S methionine biosynthetically labelled myoblast cell extracts immunoprecipitated with alpha Jo-1 positive sera and analyzed by SDS-PAGE revealed a specific band of the same molecular weight as the rHRS antigen. Our studies demonstrate that alpha Jo-1 specifically binds to antigen in the cytoplasm of cultured myoblasts. Alpha Jo-1 has been shown to inhibit HRS activity in vitro. Given the importance of aminoacyl tRNA synthetases such as HRS to intracellular protein assembly, intracytoplasmic binding and enzyme inhibition in vivo may potentially contribute to the pathogenesis of autoimmune muscle damage in PM.     

Decreased Histamine Catabolism in the Colonic Mucosa of Patients with Colonic Adenoma

Introduction Alterations in mucosal histamine degradation play an important role in various gastrotinestinal diseases including colonic adenoma. In humans, histamine can be catabolized either by oxidative deamination by diamine oxidase (DAO) or by ring methylation by histamine N-methyltransferase (HNMT). The significance of HNMT in this context was investigated for the first time in this project. Methods About 94 colonic biopsies were endoscopically obtained from 23 patients suffering from colonic adenoma and 26 biopsies from six healthy individuals. Each sample was mechanically homogenized, homogenates were cleared by centrifugation and used for determination of protein and histamine concentrations and enzyme activities of DAO and HNMT by radiometric assay. Results In adenoma patients DAO activities were slightly and HNMT activities were significantly decreased in normal mucosa compared to controls. Activities of both enzymes were significantly lower in adenoma tissue than in healthy mucosa in the same patients. A significant correlation was found between HNMT and DAO in all investigated samples. Histamine concentrations were elevated in adenoma patients. Conclusions Histamine catabolism is decreased in the colonic mucosa of patients with colonic adenoma.     

Effects of inhaled nitric oxide on inflammation and apoptosis after cardiopulmonary bypass

BACKGROUND: Cardiopulmonary bypass (CPB), a procedure often used during cardiac surgery, is associated with an inflammatory process that leads to lung injury. We hypothesized that inhaled nitric oxide (INO), which has anti-inflammatory properties, possesses the ability to modulate lung cell apoptosis and prevent CPB-induced inflammation. METHODS: Twenty male pigs were randomly classified into four groups: sham, sham plus INO, CPB, and CPB plus INO. INO (20 ppm) was administered for 24 h after anesthesia. CPB was performed 90 min into INO treatment. BAL fluid and blood were collected at time 0 (before CPB), at 4 h after beginning CPB, and 24 h after beginning CPB (T24). RESULTS: At T(24), BAL interleukin (IL)-8 levels and neutrophil percentages were elevated significantly in the CPB group. At T(24), INO reduced IL-8 concentrations and attenuated the increase of neutrophil percentage in the CPB-plus-INO group. Nitrite-plus-nitrate (NOx) concentrations were decreased significantly in groups without INO. Moreover, animals treated with INO showed higher rates of pulmonary apoptosis compared to their respective control groups except for the sham-plus-INO group, in which they were diminished. CONCLUSION: These results demonstrate that NOx production is reduced after CPB, and that INO acts as an anti-inflammatory agent by decreasing neutrophil numbers and their major chemoattractant, IL-8. INO also increases cell apoptosis in the lungs during inflammatory conditions, which may explain, in part, how it resolves pulmonary inflammation.     

Eating psychopathology in young non‐clinical adults: a pilot study of the impact of parental personality

This pilot study aims to determine the effect of parental personality factors on their grown‐up children's eating attitudes. Thirty sets of non‐clinical participants (mother, father, young adult child) completed standardized measures of narcissism, borderline personality disorder characteristics and eating pathology. Data were analysed using correlations. There were specific associations between parental personality pathology and their child's eating attitudes in young adulthood, but only in relation to fathers' levels of maladaptive narcissism. The ‘martyred’ form of narcissism in fathers was linked to bulimic attitudes in their children, while their ‘controlling’ narcissism was linked with restrictive eating attitudes. These results add to the growing body of research demonstrating paternal influences on the development of eating attitudes. Potential clinical implications for family and individual therapy are also discussed. Copyright © 2005 John Wiley & Sons, Ltd and Eating Disorders Association.     

Angiotensin-converting enzyme C-terminal catalytic domain is the main site of angiotensin I cleavage in vivo

Angiotensin-converting enzyme (ACE) plays a central role in the production of the vasoconstrictor angiotensin II. ACE is a single polypeptide, but it contains 2 homologous and independent catalytic domains, each of which binds zinc. To understand the in vivo role of these 2 domains, we used gene targeting to create mice with point mutations in the ACE C-domain zinc-binding motif. Such mice, termed ACE13/13, produce a full-length ACE protein with tissue expression identical to wild-type mice. Analysis of ACE13/13 mice showed that they produce ACE having only N-domain catalytic activity, as determined by the hydrolysis of domain specific substrates and by chloride sensitivity. ACE13/13 mice have blood pressure and blood angiotensin II levels similar to wild-type mice. However, plasma renin concentration is increased 2.6-fold and blood angiotensin I levels are increased 7.5-fold. Bradykinin peptide levels are not different from wild-type levels. ACE13/13 mice have a reduced increase of blood pressure after intravenous infusion of angiotensin I. ACE13/13 mice have a normal renal structure, but they are not able to concentrate urine after dehydration as effectively as wild-type mice. This study shows that the C-domain of ACE is the predominant site of angiotensin I cleavage in vivo. Although mice lacking C-domain activity have normal physiology under laboratory conditions, they respond less well to the stress of dehydration.     

Effects of milrinone treatment in cardiomyopathic hamsters (CHF 147) with severe congestive heart failure

The effects of oral milrinone treatment in cardiomyopathic hamsters with severe congestive heart failure (CHF) were evaluated. Strict criteria based on increase in body weight were established to define day no 1 of treatment. Survival rate of non-treated hamsters (group 1) ranged between 9 and 16 d, mean 12.9 (SEM 0.8) d, after entering the study. Hamsters treated with milrinone in drinking water (group 2a: 0.3 mg.ml-1, or group 2b: 0.6 mg.ml-1) survived between 6 and 36 d, mean 15.0(2.1) d, NS, for group 2a, and between 6 and 47 d, mean 19.6(4.0) d, NS, for group 2b. There was a significant difference between the number of hamsters that survived longer than 16 d between untreated hamsters (group 1, n = 0/12) and hamsters treated with milrinone (groups 2a, b, n = 7/24). There was no significant correlation between survival duration and milrinone daily dose nor between survival and milrinone plasma concentration at death. Milrinone treatment also significantly decreased pulmonary congestion as measured by the number of pigment containing macrophages per alveolus. No other pathological findings were modified by milrinone. It was concluded that, in addition to exerting a beneficial effect on pulmonary congestion, milrinone improved survival in some CHF hamsters. However, more studies are needed to evaluate the possibility of an arrythmogenic potential that might explain why some treated hamsters died earlier than non-treated hamsters.     

Arterial repair after stenting and the effects of GM6001, a matrix metalloproteinase inhibitor

OBJECTIVES: This study compared the extracellular matrix (ECM) and cellular responses after stenting to balloon angioplasty (BA) and to determine the late effects of matrix metalloproteinase (MMP) inhibition on arterial repair after stenting. BACKGROUND: Although stenting is the predominant form of coronary intervention, there is limited understanding of the early and late arterial response. METHODS: In a double-injury rabbit model, adjacent iliac arteries in 87 animals received BA (3.0 mm diameter) or stenting (3.0 mm NIR). Rabbits were treated for 1 week postprocedure with either GM6001 (100 mg/kg per day), an MMP inhibitor or placebo and sacrificed at 1 week or at 10 weeks' postprocedure. Arteries were analyzed for morphometry, collagen content, gelatinase activity, cell proliferation and DNA content.RESULTS: Stented arteries had significant increases in collagen content (2-fold) at 10 weeks compared to BA-treated arteries. At one week, overall gelatinase activity was increased >2-fold in stented arteries, with both 72 kD and 92 kD gelatinase activity. Stented arteries also had increases in both intimal DNA content (1.5-fold) and absolute cell proliferation (4-fold). Compared to placebo, GM6001 significantly inhibited intimal hyperplasia and intimal collagen content, and it increased lumen area in stented arteries without effects on proliferation rates. CONCLUSIONS: Stenting causes a more vigorous ECM and MMP response than BA, which involves all layers of the vessel wall. Inhibition by MMP blocks in-stent intimal hyperplasia and offers a novel approach to prevent in-stent restenosis.