Mice with an inactivation of the inducible nitric oxide synthase gene are susceptible to experimental autoimmune encephalomyelitis

Nitric oxide (NO) generated by the inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). In this study mice genetically deficient for iNOS are shown to be susceptible to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG). In iNOS (–/–) mice the course of disease was earlier in onset and more aggressive compared to control animals. A disease-relevant compensatory up-regulation of neuronal (n)NOS and endothelial (e)NOS with increased production of NO in iNOS (–/–) mice is excluded by 1) the failure to detect increased nNOS and eNOS mRNA, 2) the absence of detection of nitrosylated tyrosine residues in EAE tissue indicating absence of NO-derived peroxynitrite, and 3) the lack of disease-preventing effects of N^G-nitro-L -arginine methylester. In conclusion, these results do not support the hypothesis that NO is crucial for the development of EAE.     

Effects of physostigmine on scopolamine–induced changes in quantitative electroencephalogram and cognitive performance

The effects of physostigmine on scopolamine-induced changes were investigated in a randomized, double-blind cross-over study utilizing quantitative electroencephalogram (qEEG) and cognitive tasks. Ten healthy male volunteers received scopolamine 0·6 mg subcutaneously. After 90 min, single doses of either 0·5, 1·0 and 2·0 mg physostigmine salicylate or placebo were administered subcutaneously in randomized order. qEEG, cognitive function and the visual analogue scale were recorded before and at 1, 2, 3, 4, 6, and 8 h after scopolamine administration; that was 0·5, 1·5, 2·5, 4·5, and 6·5 h after physostigmine administration. Scopolamine produced an increase in delta (1·25–4·50 Hz) and theta power (4·75–6·75 Hz) in qEEG 1 h after administration compared to baseline, while physostigmine decreased the spectral delta power density in qEEG compared to placebo. The maximal effect of physostigmine was seen up to 1·5 h after injection. A dose-dependent reversal of the scopolamine induced decrements in cognitive performance was found 0·5 h after administration of physostigmine. Psychometric tests sensitively discriminated between the doses of physostigmine, and showed dose- and time-dependent effects. The results suggest that physostigmine may reverse the scopolamine-induced changes in both qEEG and cognitive function. This reversal was temporary and of short duration. © 1998 John Wiley & Sons, Ltd.     

Anxiety as a predictor of response to interpersonal psychotherapy for recurrent major depression: An exploratory investigation

Major depression and anxiety frequently co-occur, but the implications for psychological treatments have rarely been studied. We examined predictors of acute response to interpersonal psychotherapy in 134 consecutively treated female outpatients with recurrent unipolar depression. Women who failed to remit with interpersonal psychotherapy alone experienced higher levels of somatic anxiety, were more likely to meet criteria for lifetime panic disorder, were more likely to meet criteria for nonendogenous or nonmelancholic depression, and reported greater vocational impairment, higher levels of global severity, a longer duration of the index episode, and, somewhat surprisingly, lower levels of social impairment at pretreatment evaluation. A series of backwards stepping logistic regression analyses showed higher levels of baseline somatic anxiety and social functioning to be the most consistent predictors of nonresponse. Our findings strengthen existing evidence that concomitant anxiety can adversely affect the outcome of interpersonal therapy for depression. Depression and Anxiety 8:135–141, 1998. © 1998 Wiley-Liss, Inc.     

Structured therapeutic writing tasks as an adjunct to treatment in eating disorders

Eating disorder patients, especially those with anorexia nervosa, are experientially avoidant. This group of patients finds talking treatments difficult and many standard psychotherapeutic techniques are difficult to implement. This paper discusses why therapeutic writing might be a useful adjunct to the treatment of eating disorders. Different types of therapeutic writing exercises may be useful at different stages of treatment and might aid the therapeutic process in different ways. The limitations of therapeutic writing are also discussed. Copyright © 2002 John Wiley & Sons, Ltd and Eating Disorders Association.     

Histological diagnosis of Helicobacter pylori gastritis is predictive of a high risk of gastric carcinoma

Chronic Helicobacter pylori infection has been identified as a major risk factor for the subsequent development of gastric carcinoma. On the basis of seroepidemiological studies the relative risk for infected persons was estimated to range between 3 and 6. Our study attempted to determine the relative risk of gastric carcinoma in H. pylori-infected individuals based on the histological evaluation of gastritis in gastric carcinoma patients in the light of a declining prevalence of H. pylori infection in Western countries. We histologically determined the H. pylori infection rate in 215 patients with early gastric carcinoma (tumor stage pT1), and compared it with that of 215 asymptomatic persons matched by age and sex who were tested by the 13C urea breath test. On the basis of these data an odds ratio of 16.7 (CI 9.6–29.1) was calculated for the relative risk of developing gastric carcinoma in H. pylori-infected people. The histological diagnosis of gastritis permits a separate risk assessment for patients with autoimmune gastritis, and by excluding these patients from the analysis we calculated an odds ratio for H. pylori-infected persons of 150 (CI 36.4–622.9). The endoscopic-histological diagnosis of H. pylori infection is associated with an increased risk of the subsequent development of gastric carcinoma of approximately 150-fold compared with H. pylori-negative patients who do not have chronic atrophic corpus gastritis of the autoimmune type (type A gastritis). Int. J. Cancer 73:837–839, 1997. © 1997 Wiley-Liss, Inc.     

Developmentally regulated masking of an intracellular epitope of the 180 kDa isoform of the neural cell adhesion molecule NCAM

The neural cell adhesion molecule NCAM is a cell surface glycoprotein that occurs in several isoforms. It was previously shown that the largest 180-kDa isoform of NCAM (NCAM 180) accumulates at sites of cell contact and in postsynaptic densities and may be responsible for the stabilization of cell contacts by its interaction with the membrane-cytoskeleton linker protein brain spectrin. In immunohistochemical studies on the expression of the NCAM 180, we noticed that two NCAM 180 specific monoclonal antibodies, termed 481 and D3, showed different patterns of immunoreactivity in sections of fresh-frozen adult mouse brain. Here we show that the D3-specific, but not the 481-specific epitope becomes inaccessible to the antibody during development of the hippocampal formation, coincident with the establishment of stable cell-cell contacts. In contrast, in the olfactory bulb with its continually regenerating olfactory nerve fibers, both NCAM 180 antibodies remain fully immunoreactive throughout development and adulthood. We also show that the D3-specific epitope becomes inaccessible in primary cerebellar neuron cultures with time in culture. Electrophoretic separation of hippocampal membrane proteins under nondenaturating conditions showed NCAM to be present in protein complexes of different molecular weights at different developmental stages. We propose that NCAM is involved in the formation of developmentally regulated, noncovalent complexes with as yet unknown partner molecules that could be responsible for the masking of the D3-specific epitope. J. Neurosci. Res. 49:161–175, 1997. © 1997 Wiley-Liss, Inc.     

Morphological analysis of the blue cone pathway in the retina of a New World monkey,the marmoset Callithrix jacchus

We have studied the components of the short wavelength-sensitive (SWS or “blue”) cone pathway in the retina of a New World primate, the marmoset Callithrix jacchus. Of particular interest was the small bistratified ganglion cell, which has been identified in macaque monkey to be the morphological substrate of the blue-ON cell (Dacey and Lee [1994] Nature 367:731–735). Small bistratified cells were intracellularly filled with Neurobiotin in an in vitro retinal wholemount preparation. Their morphology, size, and level of dendritic stratification were similar to their homologues in macaque and human retina. A number of different antibodies were applied to vertical cryostat sections, some of which were cut through the processes of injected small bistratified or parasol ganglion cells. We used antibodies against cholecystokinin (CCK) to label blue cone bipolar cells, and antibodies against the human SWS cone photopigment to label SWS cones. Double-labelled preparations showed that blue cone bipolar cell dendrites contact SWS cone pedicles, and the inner dendrites of the small bistratified cell are costratified with the axon terminals of blue cone bipolar cells. A monoclonal antibody against calbindin was used to label a subpopulation of bipolar cells that stratifies in the outer half of the inner plexiform layer. The axon terminals of these bipolar cells occasionally cross the outer dendrites of small bistratified cells and show extensive costratification with the dendrites of OFF parasol cells. We conclude that an SWS cone pathway with similar connectivity is a preserved feature of the primate visual system. J. Comp. Neurol. 379:211–225, 1997. © 1997 Wiley-Liss, Inc.