Depression-executive dysfunction syndrome in stroke patients.

OBJECTIVE: It has been suggested that executive dysfunction could be the core defect in patients with geriatric or vascular depression, and that this depression-dysexecutive syndrome (DES) might be related to frontal-subcortical circuit dysfunction. The authors tested this hypothesis in 158 poststroke patients, of whom 21 had both depression and executive dysfunction. Methods: In this cross-sectional cohort study, a neurological, psychiatric, and neuropsychological examination was carried out 3 months after ischemic stroke, and brain infarcts, white-matter changes, and brain atrophy were recorded by MRI. RESULTS: The 21 patients with DES had significantly more brain infarcts affecting their frontal-subcortical circuit structures than the 137 patients without DES, or the 41 patients with depression but without executive dysfunction. Patients with DES also had more severe depressive symptoms and worse psychosocial functioning, and they coped less well in complex activities of daily living. CONCLUSIONS: DES is a valid concept and may define a subgroup of poststroke patients with frontal-subcortical pathology and with distinct prognosis and treatment options.     

Search for intracranial aneurysm susceptibility gene(s) using Finnish families

Background

Cerebrovascular disease is the third leading cause of death in the United States, and about one-fourth of cerebrovascular deaths are attributed to ruptured intracranial aneurysms (IA). Epidemiological evidence suggests that IAs cluster in families, and are therefore probably genetic. Identification of individuals at risk for developing IAs by genetic tests will allow concentration of diagnostic imaging on high-risk individuals. We used model-free linkage analysis based on allele sharing with a two-stage design for a genome-wide scan to identify chromosomal regions that may harbor IA loci.

Methods

We previously estimated sibling relative risk in the Finnish population at between 9 and 16, and proceeded with a genome-wide scan for loci predisposing to IA. In 85 Finnish families with two or more affected members, 48 affected sibling pairs (ASPs) were available for our genetic study. Power calculations indicated that 48 ASPs were adequate to identify chromosomal regions likely to harbor predisposing genes and that a liberal stage I lod score threshold of 0.8 provided a reasonable balance between detection of false positive regions and failure to detect real loci with moderate effect.

Results

Seven chromosomal regions exceeded the stage I lod score threshold of 0.8 and five exceeded 1.0. The most significant region, on chromosome 19q, had a maximum multipoint lod score (MLS) of 2.6.

Conclusions

Our study provides evidence for the locations of genes predisposing to IA. Further studies are necessary to elucidate the genes and their role in the pathophysiology of IA, and to design genetic tests.     

Isolation of a Trichoderma reesei cDNA encoding GTP: a-d-mannose-1-phosphate guanyltransferase involved in early steps of protein glycosylation

A cDNA coding for GTP: α-d-mannose-1-phosphate guanyltransferase (MPG1 transferase) (EC 2.7.7.13) was isolated from a cDNA library of the Trichoderma reesei RutC-30 strain by suppression of the yeast Saccharomyces cerevisiae mutation in the DPM1gene encoding mannosylphosphodolichol (MPD) synthase. The nucleotide sequence of the 1.6 kb-long cDNA revealed an ORF which encodes a protein of 364 amino acids. Sequence comparisons demonstrate 70% identity with the S. cerevisiae guanyl transferase gene (MPG1) and 75% identity with the Schizosaccharomyces pombe homologue. No similarity was found with the MPD synthase encoded by the S. cerevisiae DPM1 gene. The possibility that cloned cDNA encodes a product with a MPD synthase activity was also excluded by transforming a heterozygous S. cerevisiae dpm1::LEU2/DPM1 diploid, which did not lead to the restoration of viability of the dpm1 spores. Simultaneously, a significant increase in MPG transferase activity, as compared with the wild-type yeast, was observed in cellular extracts when the mpg1 cDNA from Trichoderma was expressed in the S. cerevisiae dpm1-6 mutant. Received: 21 July 1997 / 24 April 1998     

Primary gastrointestinal stromal tumor of the esophagus in an HIV-positive patient

We describe a rare case of malignant gastrointestinal stromal tumor (GIST) of the esophagus presenting in an HIV-positive man. Not only did the tumor arise from an unusual anatomic site for GIST, namely, the esophagus, but it also had a predominant epithelioid cell morphology that is uncommon and preferentially associated with aggressive behavior. Exhaustive immunohistochemical studies showed strong reactivities to the classic GIST marker, CD34, and to the current more sensitive and more specific GIST marker, CD117/ c-kit protein. This immunophenotype corresponded to that of stromal tumors arising in the more common sites like stomach and small intestine as well as to that of a reported series of esophageal GISTs in the general population. Mutations of the c-kit protein was detected in the tumor, confirming previous observations. This further documents that esophageal GIST and the more common benign esophageal spindle cell lesions are pathologically distinct entities and despite its rarity, esophageal GIST should be recognized by pathologists and clinicians. The occurrence of this tumor in an HIV-positive patient is coincidental, and it resulted in an extremely unusual metastatic site that has not been reported for GISTs.     

1H MRS of a boron neutron capture therapy 10B-carrier,L-p-boronophenylalanine-fructose complex,BPA-F: phantom studies at 1.5 and 3.0 T

The quantification of a BNCT 10B-carrier, L-p-boronophenylalanine-fructose complex (BPA-F), was evaluated using 1H magnetic resonance spectroscopy (1H MRS) with phantoms at 1.5 and 3.0 T. For proper quantification, relaxation times T1 and T2 are needed. While T1 is relatively easy to determine, the determination of T2 of a coupled spin system of aromatic protons of BPA is not straightforward with standard MRS sequences. In addition, an uncoupled concentration reference for aromatic protons of BPA must be used with caution. In order to determine T2, the response of an aromatic proton spin system to the MRS sequence PRESS with various echo times was calculated and the product of the response curve with exponential decay was fitted to the measured intensities. Furthermore, the response curve can be used to correct the intensities, when an uncoupled resonance is used as a concentration reference. BPA was quantified using both phantom replacement and internal water referencing methods with accuracies of +/- 5% and +/- 15%. Our phantom results suggest that in vivo studies on BPA concentration determination will be feasible.     

Localization of [Met5]- and [Leu5]-enkephalin-like immunoreactivity in nerve terminals in human paravertebral sympathetic ganglia

Both [Leu⁵]- and [Met⁵]-enkephalin have been localized immunohistochemically in nerve fibres and in small, intensely fluorescent cells of adult human sympathetic ganglia. The nerve fibres showing enkephalin-like immunoreactivity formed a network varying in density around the sympathetic neurons, some being closely related to the perikarya. No labelled neuronal cell bodies were found. No structures within the ganglion were labelled after reaction with antibodies to vasoactive intestinal polypeptide, adrenocorticotrophin or substance P. No differences between the distributions of [Leu⁵]-and [Met⁵]-enkephalin-like immunoreactivities were found.The physiological roles of enkephalins are still unknown, but it is possible that they might act as neurotransmitters or neuromodulators in the human sympathetic nervous system.