The effect of erroneous responses on response monitoring in patients with major depressive disorder: a study with event-related potentials

Perceived failure is reported to have detrimental effects on subsequent performance in patients with major depressive disorder. We investigated the error-related negativity (ERN)/error negativity (Ne), an electrophysiological correlate of response monitoring, using a 64-channel EEG. Sixteen patients with DSM-IV major depressive disorder and 16 matched controls participated in an Eriksen flanker task with continuous performance feedback that signaled monetary reward. Compared to controls, patients with major depressive disorder showed a less negative ERN/Ne in error trials following error trials. This result might reflect impaired response monitoring processes in major depressive disorder resulting from an underactivity in a central reward pathway and/or a deficit in strategic reasoning.     

Odor cue mediation of alcohol aversion learning in rats lacking gustatory neocortex.

Normal rats presented with a 5% alcohol solution followed by lithium chloride-induced illness quickly learned to avoid drinking alcohol. After training, the rats also avoided drinking water in the presence of the alcohol odor alone, whether tested immediately or 1 month later. In Experiment 1, rats with gustatory neocortex (GN) ablations also developed strong alcohol aversions when the alcohol solution was paired with illness. They also showed normal avoidance of drinking in the presence of the alcohol odor alone when tested soon after training. In Experiment 2, when normal rats were trained to avoid alcohol, given GN ablations, and then tested for retention 1 month later, avoidance of drinking water in the presence of the odor alone was significant but attenuated somewhat in relation to trained control rats. These data support the hypothesis that rats lacking GN partially acquire alcohol aversions by using odor cues and confirm that associative learning is intact in these rats despite the fact that GN rats display significant deficits in aversion learning when only tastes are paired with illness.     

Structure and expression of the gene for Pv200, a major blood-stage surface antigen of Plasmodium vivax.

Molecular cloning and structure analysis of the gene encoding the Pv200 protein of the Sal-1 strain of Plasmodium vivax revealed an overall identity of 34–37% when the deduced amino acid sequence was compared with the sequences of various major merozoite surface antigens of Plasmodium falciparum, Plasmodium yoelii and Plasmodium chabaudi. When the Sal-1 Pv200 sequence was compared with the corresponding sequence from the Belèm strain of P. vivax, it was found that the two merozoite surface antigens were relatively well conserved with an overall amino acid sequence identity of 81%. A region of 23 repeated glutamine residues, found in the sequence of the Belèm isolate was not found, however, in the Sal-1 sequence. Amino-and carboxy-terminal domains of the Pv200 protein were expressed in the yeast Saccharomyces cerevisiae. Each recombinant protein was shown to react with antibodies in sera from splenectomized Bolivian Saimiri monkeys that had been infected previously with P. vivax, and in human sera from individuals with a history of exposure to vivax malaria. The availability of recombinant DNA-derived Pv200 proteins will now allow a full assessment of their utility in the diagnosis and immunoprophylaxis of the benign tertian malaria associated with P. vivax infection.     

Induction of micronuclei in metabolically competent rat hepatoma cell lines by the promutagens 7, 12-dimethylbenz[a]anthracene, benzo[a]pyrene and cyclophosphamide

The capability of two rat hepatoma cell lines, H4IIEC3/G- and2sFou, to detect genotoxicity of xenobiotics, was evaluatedin a micronucleus assay. In this system, the cells act as theactivation source as well as the target cells for the DNA damage.The study was performed using 7, 12-dimethylbenz[a]anthracene,benzo[a]pyrene and cyclophosphamide, as pro-mutagens and mitomycinC as a direct acting mutagen. In both cell lines a significantmicronucleus induction was observed after exposure to each testcompound, starting from 25 nM for 7,12-dimethylbenz[a]anthracene,8 µM for benzo[a]pyrene, 0.5 mM for cyclophosphamide and0.4 µM for mitomycin C. A period of 24 h treatment and48 h growth was sufficient for induction and expression of micronuclei.The two hepatoma lines behave in a similar way with regard tothe pro-mutagen activation. The results obtained in this studywith these differentiated hepatoma lines demonstrate that theyare metabolically competent to activate the pro-mutagens 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene and cyclophosphamideinto their biologically active metabolites as measured by micronucleusinduction in our experiments. However, the variable dose responsesto 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene in someof the repeated experiments, suggest unstable activity of enzymesinvolved in polycyclic aromatic hydrocarbons metabolism in thesecell lines.     

Becker's X-linked muscular dystrophy histological,enzyme-histochemical,and ultrastructural studies of two cases,originally reported by Becker

Summary Muscle biopsies of two patients originally reported in the Göttingen family by Becker (1962) that formed the basis of separating a benign X-linked muscular dystrophy from the rapidly progressive Duchenne-type X-linked muscular dystrophy, revealed mild pathological changes in the younger patient and more advanced in the older one, consisting of increased spectra of fiber diameters, endomysial fibrosis, angulated fibers, pyknotic nuclear clumps and small groups of atrophic fibers. Essentially, both biopsies showed the same changes, but of different severity, possibly due to the differences in age and muscle biopsy sites. These changes were regarded myopathic, but a neurogenic component was suggested. Our observations accord well with those of a larger series (Bradley et al., 1978) where both electromyography and histopathology revealed a mixed myopathic-neurogenic pattern in patients with Becker-type dystrophy. Differential diagnostic aspects encompass Duchenne's muscular dystrophy, the other hereditary dystrophies and X-linked proximal spinal muscular atrophies. The precise nature of Becker-type muscular dystrophy requires morphological data on peripheral nerves, spinal roots and spinal cord anterior horn cells as well as sequential biopsy analysis to substantiate the primary site of pathology. However, on the basis of available data, it seems reasonable to suggest that the early changes of degeneration/regeneration which are accompanied by a markedly elevated CPK eventuate in the histopathologic and electromyographic patterns illustrated in these two patients with Beckertype dystrophy.These studies have in part been supported by a grant from The Volkswagen-Stiftung (HHG). Parts of this paper have been presented at the Neurochemical Group Symposium, Bath University, March 30, 1977, and at the Annual Meeting of the German Society of Neuropathology, Tübingen University, October 17–19, 1977     

Enhanced B7 costimulatory molecule expression in inflammatory human sural nerve biopsies

OBJECTIVES: To define the role of the costimulatory molecules B7-1 and B7-2 in inflammatory disorders of the peripheral nervous system. B7 molecules are essential for effective antigen presentation and may determine the differentiation of T cells into a Th-1 or Th-2 phenotype, thus modulating immune response and disease course. METHODS: Forty nine sural nerve biopsies from patients with neuroborreliosis, Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), CIDP variants and hereditary neuropathies, and those with no detectable abnormality were investigated. The expression of B7-1 and B7-2 mRNA and protein was investigated by polymerase chain reaction (PCR) and immunocytochemistry. RESULTS: B7-1 mRNA was strongly upregulated in both cases of neuroborreliosis, in two cases of GBS and one case of variant CIDP. Moderate to low levels were detected in the remaining GBS and CIDP biopsies and were rarely found in a non-inflammatory control group consisting of hereditary neuropathy and normal nerves. At the immunocytochemical level, strong expression of B7-1 protein was found in both neuroborreliosis cases, and moderate or low expression in six of eight GBS cases and seven of 17 CIDP cases investigated, whereas only one of five non-inflammatory control nerves showed staining, which was very weak. In neuroborreliosis, B7-1 protein was found very pronounced in epineurial infiltrates, whereas in GBS and CIDP, labelling was predominantly endoneurial and localised to putative macrophages. B7-2 mRNA and protein were expressed only at low levels in neuroborreliosis and selected autoimmune neuropathy cases, and were essentially absent from non-inflammatory controls. CONCLUSIONS: B7 molecules are expressed in the peripheral nervous system and regulated during disease, and their presence in macrophages underlines the putative function of endoneurial macrophages as local antigen presenting cells in the immunopathology of peripheral nerve. B7-1 rather than B7-2 is preferentially upregulated, possibly promoting the induction of a Th-1-type T cell response within the nerve.     

Tumor recurrence and survival in patients treated for thymomas and thymic squamous cell carcinomas: a retrospective analysis.

PURPOSE: Thymic epithelial tumors (TET) are rare epithelial neoplasms of the thymus with considerable histologic heterogeneity. This retrospective study focused on the correlation of WHO-defined TET histotypes with survival and tumor recurrence in a large cohort of patients receiving different modes of treatment. PATIENTS AND METHODS: Two hundred twenty-eight patients were followed for up to 21 years (median, 60 months; range, 1 to 252 months) after primary surgery. Forty-two patients received adjuvant radiotherapy (mean dose, 53 Gy), and 33 patients received adjuvant chemotherapy. RESULTS: Seventy-six (88%) of 86 patients with WHO type A, AB, and B1 thymomas were treated by surgery alone, with three tumor relapses after 3 to 10 years (median, 3.4 years). Twelve of 67 patients with WHO type B2 and B3 thymomas in Masaoka stages I and II were treated by adjuvant radiotherapy without evidence of tumor recurrence after 1 to 12 years (median, 4 years). Among 75 patients with B2 and B3 thymomas with incomplete resection or a tumor stage III or higher, the recurrence rate was 34% (n = 23) after 0.5 to 17 years (median, 5 years) in patients receiving adjuvant radiochemotherapy, compared to 78% (seven of nine patients) in patients without adjuvant radiochemotherapy. Incomplete tumor resection was associated with a high recurrence rate (65%) and a poor prognosis (P <.01). CONCLUSION: The long-term outcome of TET patients is related to tumor stage, WHO histotype, completeness of surgical removal, and type of treatment. Prospective trials are warranted to formally address the efficacy of adjuvant therapy in the treatment of localized and advanced malignant TETs.