Response amplification in sensory-specific cortices during crossmodal binding

Integrating information across the senses can enhance our ability to detect and classify stimuli in the environment. For example, auditory speech perception is substantially improved when the speaker's face is visible. In an fMRI study designed to investigate the neural mechanisms underlying these crossmodal behavioural gains, bimodal (audio-visual) speech was contrasted against both unimodal (auditory and visual) components. Significant response enhancements in auditory (BA 41/42) and visual (V5) cortices were detected during bimodal stimulation. This effect was found to be specific to semantically congruent crossmodal inputs. These data suggest that the perceptual improvements effected by synthesizing matched multisensory inputs are realised by reciprocal amplification of the signal intensity in participating unimodal cortices.     

Higher levels of antibodies against the psoriasis-associated antigen pso p27 in cerebrospinal fluid from patients with low back pain and sciatica

STUDY DESIGN: A prospective study comparing the presence of antibodies against the psoriasis-associated antigen pso p27 in pain-free control subjects and patients with low back pain and/or sciatica. OBJECTIVES: To analyze the amount of local inflammation present in human lumbar disc disorders, using anti-pso p27 antibodies in the cerebrospinal fluid as a marker and to analyze whether pain intensity correlates with this marker of inflammation. SUMMARY OF BACKGROUND DATA: Pso p27 is a major antigen in psoriasis that is also present, mostly locally, in other inflammatory disorders, such as sarcoidosis, inflammatory bowel disease, and ankylosing spondylitis, inflammation is also thought to play a major role in the generation of lumbar and radicular pain in degenerative disc disorders. METHODS: Anti-pso p27 antibodies in cerebrospinal fluid were quantified using an indirect enzyme-linked immunosorbent assay with pso p27 obtained from patients with psoriasis for use as an antigen. Fifteen patients with spinal stenosis, 11 patients without myelographic disc herniation, 17 patients with disc herniation, and 24 pain-free patient control subjects were studied. RESULTS: Significantly higher levels of anti-pso p27 antibodies were found in patients with myelographic signs of disc herniation than in with patients with no signs of herniation, patients with spinal stenosis, and control subjects. Patients with no known signs of disc herniation and patients with myelographic signs of spinal stenosis (< 10 mm in diameter) caused by degenerative changes, had higher levels of anti-pso p27 antibodies than did control subjects. However, these differences reached only borderline statistical significance. CONCLUSIONS: The results support those in previous reports, that inflammation probably plays an important role in degenerative disk disorders, particularly in disk herniations. That there was no correlation between pain intensity and anti-pso p27 activity indicates that the antigen is probably not essential in pain generation per se. The results may indicate that pso p27 is expressed secondary to, not as an initiator of, inflammation.     

Effects of GABA,dopamine, and substance P on the release of newly synthesized 3H-5-hydroxytryptamine from rat substantia nigra in vitro

Summary The effects of GABA, substance P and dopamine on the release of newly synthesized ³H-5-HT were investigated, using slices of rat substantia nigra superfused with l-³H-tryptophan in vitro. GABA (50 M) had no inhibitory effect on the potassium-evoked-release of ³H-5-HT. Substance P (50 M) and eledoisin (50 M) stimulated the spontaneous release of ³H-5-HT. This effect seems to be indirect and is possibly mediated by dopaminergic neurones, since the dopamine antagonist drug -flupenthixol (1 M) abolished the substance P-evoked release of 5-HT. Furthermore, it was found that substance P (10 M) stimulated ³H-dopamine release from nigral slices in vitro and the dopaminergic agonist apomorphine (50 M) also stimulated ³H-5-HT release. Substance P may, therefore, activate nigral dopaminergic neurones which then release dopamine from their dendrites. The release of dopamine may in turn stimulate 5-HT release from terminals of the raphe-nigral pathway.     

Pharmacological mechanisms and animal models of cognition

Requirements for an effective animal model of cognition are discussed with special reference to the cholinergic hypothesis of Alzheimer's disease. It is argued, with reference to research on vasopressin and ACE inhibitors, that many putative animal models of cognition lack predictive clinical validity because they either confound the effects of cognitive and arousal processes, or fail to model a specific component of cognitive functioning. A survey of recent research on the cholinergic hypothesis illustrates how these weaknesses can be overcome. Studies involving scopolamine and basal forebrain excitatory amino acid lesion models of the cholinergic deficit in Alzheimer's disease have employed a delayed-matching-to-position test in rodents which, unlike passive avoidance, allows the effects of memory and attentional variables to be distinguished. In combination with recent human studies, these experiments suggest that the cholinergic system has a major role in executive control of attentional resources, and lead to the recommendation of a 'top down' strategy in the investigation of neurochemical processes and pharmacological mechanisms underlying cognition.     

Independent prognostic importance of microvessel density in endometrial carcinoma.

Angiogenesis is thought to be an important factor for tumour growth and metastatic spread, and microvessel counts may provide useful prognostic information for several tumour types. To investigate the prognostic impact of angiogenesis in endometrial carcinoma patients, the intratumour microvessel density, which was determined immunohistochemically, has been related to survival. Sixty patients with endometrial carcinoma with long (median 19 years) and complete follow-up have been studied. Patients with increased mean microvessel density (MVDmean > 68 mm2) had a significantly shorter 5-year survival compared with the rest (57% vs 90%, P = 0.004). In multivariate survival analyses, MVDmean had an independent prognostic impact (P = 0.03) when FIGO stage, histological type, histological grade as well as nuclear p53 protein expression was adjusted for. These findings indicate that intratumour microvessel density may contribute additional prognostic information to that obtained from the known risk factors and may be helpful in identifying endometrial carcinoma patients at high risk for disease progression.     

The role of nigral and thalamic output pathways in the expression of oral stereotypies induced by amphetamine injections into the striatum

Microinjections of amphetamine into the ventrolateral striatum (VLS) elicit a striking behavioral syndrome characterized by compulsive oral and forelimb motor stereotypies. The neural pathways that mediate these behavioral responses downstream from the striatum have not yet been identified. In a series of experiments, we investigated the involvement of the substantia nigra pars reticulata (SNr) and the ventromedial nucleus of the thalamus (VMT) in the mediation of this behavioral syndrome. We demonstrated that lidocaine-induced reversible inactivation of the SNr reduced amphetamine-induced stereotyped biting and gnawing behaviors, suggesting that the nigral output pathway plays a significant role in the expression of these behavioral responses. In turn, injections of lidocaine into the VMT only transiently reduced amphetamine-stimulated biting and increased stereotyped gnawing and paw nibbling, suggesting that the expression of oral stereotypies induced by amphetamine injections into the VLS is not dependent on thalamocortical feedback.     

Flow cytometric deoxyribonucleic acid index: a prognostic factor in endometrial carcinoma

In a prospective study, flow cytometric deoxyribonucleic acid analyses were performed on cell samples from benign and malignant tumors of the endometrium and benign endometrium. No ploidy aberrations were found in normal endometrium. Of 52 cases with adenocarcinomas, 38 (73%) were diploid and 14 (27%) aneuploid. Both the frequency and the degree of aneuploidy were correlated to histologic tumor grade but not to other prognostic variables such as International Federation of Gynecologists and Obstetricians stage, depth of myometrial invasion, or patient age. Patients with aneuploid tumors had a higher recurrence rate and shorter disease-free intervals as compared to those with diploid tumors. Similarly, death rates were higher and the median survival was shorter in the aneuploid group. Flow cytometric ploidy determination may therefore serve as an important prognostic parameter.     

A role for receptors of N-methyl-D-aspartic acid in the discriminative stimulus properties of phencyclidine

Ketamine and (+)-N-allylnormetazocine ((+)-NANM) were found to generalize in a rat operant drug discrimination paradigm to the interoceptive stimulus induced by phencyclidine (PCP). Intraperitoneal administration of the non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, MK-801, and intracerebroventricular injection of the competitive antagonist, 2-DL-amino-7-phosphonoheptanoic acid (2-APH), also resulted in a dose-dependent generalisation to the PCP discriminative stimulus. The results suggest that NMDA receptor antagonism may play an important role in the mediation of the discriminative stimulus properties of PCP. The low potency of MK-801 and 2-APH to displace [3H](+)-NANM binding in vitro argues against an involvement of the haloperidol-sensitive sigma recognition site in the behaviour.