Gating of local network signals appears as stimulus-dependent activity envelopes in striate cortex

Neuronal activity often is treated as a composition of a stimulus-driven component and a second component that corrupts the signal, adding or deleting spikes at random. Standard quantitative methods such as peristimulus histograms and Fourier analysis use stimulus-locked averaging to enhance detection of the driven component of neuronal responses and de-emphasize the "noise." However, neural activity also includes bursts, oscillations, and other episodic events that standard averaging methods overlook. If this activity is stimulus independent, it can be characterized by standard power spectral analysis (or autocorrelation). But activity that is excited by (but not temporally locked to) the visual stimulus cannot be characterized by averaging or standard spectral analysis. Phase-locked spectral analysis (PLSA) is a new method that examines this "residual" activity-the difference between the individual responses to each cycle of a periodic stimulus and their average. With PLSA, residual activity is characterized in terms of temporal envelopes and their carriers. Previously, PLSA demonstrated broadband interactions between periodic visual stimuli and fluctuations in the local field potential of macaque V1. In the present study, single-unit responses (SUA) from parafoveal V1 in anesthetized macaque monkey are examined with this technique. Recordings were made from 21 neurons, 6 of which were recorded in pairs along with multiunit activity (MUA) from separate electrodes and 8 of which were recorded along with MUA from the same electrode. PLSA was applied to responses to preferred (orientation, direction, and spatial frequency) and nonpreferred drifting gratings. For preferred stimuli, all cells demonstrated broadband (1-10 Hz and higher) residual activity that waxed and waned with the stimulus cycle, suggesting that changes in the residual activity are introduced routinely by visual stimulation. Moreover, some reconstructed envelopes indicate that the residual activity was sharply gated by the stimulus cycle. Oscillations occasionally were seen in the power spectrum of single units. Phase-locked cross-spectra were determined for 3 SUA/SUA pairs and 11 SUA/MUA pairs. Residual activity in the cross-spectra was generally much less than the residual activity determined separately from each neuron. The reduction in the residual activity in the cross-spectra suggests that nearby neurons may gate inputs from distinct and relatively independent neuronal subpopulations that together generate the background rhythms of striate cortex.     

A potential mechanism for fumonisin B(1)-mediated hepatocarcinogenesis: cyclin D1 stabilization associated with activation of Akt and inhibition of GSK-3beta activity

Fumonisin B(1) (FB(1)) is a worldwide corn contaminant and has been epidemiologically linked to the high incidence of human esophageal cancer in South Africa and China. FB(1) is hepatocarcinogenic in rats by an unknown mechanism. Inhibition of ceramide synthase and disruption of membrane phospholipids have been shown to be mechanisms of toxicity. Here we show overexpression of cyclin D1 protein in both preneoplastic and neoplastic liver specimens obtained from a long-term feeding study of FB(1) in rats. In rats fed FB(1) short-term, cyclin D1 protein levels in liver were increased up to five-fold in a dose-responsive manner. Northern blot analysis demonstrated no increase in mRNA levels of cyclin D1. 2D electrophoresis of cyclin D1 protein in FB(1)-treated samples showed a distinct pattern of migration (presence of less negatively charged form of the protein) that differed from controls. Recently, it has been shown that phosphorylation of cyclin D1 by glycogen synthase kinase 3beta (GSK-3beta) on a single threonine residue (Thr-286) positively regulates proteosomal degradation of cyclin D1. In FB(1)-treated samples we detected GSK-3beta phosphorylated on serine 9; activated protein kinase B (Akt) appears to be responsible for this activity-inhibiting phosphorylation. These findings suggest that overexpression of cyclin D1 results from stabilization due to a lack of phosphorylation mediated by GSK-3beta. We also observed an increase in cyclin dependent kinase 4 (Cdk4) complexes with cyclin D1 in FB(1)-treated samples; additionally, elevated Cdk4 activity was shown by increased phosphorylation of the retinoblastoma protein. In summary, the activation of Akt leads to increased survival, inhibition of GSK-3beta activity and post-translational stabilization of cyclin D1, all events responsible for disruption of the cell cycle G(1)/S restriction point in hepatocytes. This is the first report suggesting the mechanism by which FB(1) acts as a carcinogen.     

Quantitative diagnosis of stress-induced myocardial ischemia using analysis of contrast echocardiographic parametric perfusion images.

AIMS: Parametric imaging of myocardial perfusion provides useful visual information for the diagnosis of coronary artery disease (CAD). We developed a technique for automated detection of perfusion defects based on quantitative analysis of parametric perfusion images and validated it against coronary angiography. METHODS AND RESULTS: Contrast-enhanced, apical 2-, 3- and 4-chamber images were obtained at rest and with dipyridamole in 34 patients with suspected CAD. Images were analyzed to generate parametric perfusion images of the standard contrast-replenishment model parameters A, beta and A.beta. Each parametric image was divided into six segments, and mean parameter value (MPV) was calculated for each segment. Segmental MPV ratio between stress and rest was defined as a flow reserve index (FRI). Receiver operating characteristics (ROC) analysis was used in a Study group (N=17) to optimize FRI threshold and the minimal number of abnormal segments per vascular territory (LAD and non-LAD), required for automated detection of stress-induced perfusion defects. The optimized detection algorithm was then tested prospectively in the remaining 17 patients (Test group). LAD and non-LAD stenosis >70% was found in 19 and 17 patients, respectively. In the Study group, FRI threshold was: LAD=0.95 and non-LAD=0.68, minimal number of abnormal segments was four and two, correspondingly. Sensitivity, specificity and accuracy in the Test group were: 75%, 67% and 71% in the LAD, and 75%, 75% and 75% in the non-LAD territories. CONCLUSION: Automated quantitative analysis of contrast echocardiographic parametric perfusion images is feasible and may aid in the objective detection of CAD.     

Gastroduodenal polyps in patients with familial adenomatous polyposis

A review of the endoscopy reports and pathology results from esophagogastroduodenoscopy (EGD) of all patients with familial adenomatous polyposis (FAP) undergoing such an examination was performed. Two hundred fortyseven patients were identified, with an overall prevalence of duodenal adenomas of 66 percent and of fundic gland polyps of 61 percent. Analysis of our more recent experience (1986 to 1990) shows the prevalence to be 88 percent and 84 percent, respectively. A normal-appearing papilla was adenomatous in 50 percent of cases. No case of periampullary carcinoma developed in patients under surveillance. Routine EGD is indicated for patients with FAP. Duodenal adenomas and fundic gland polyps will occur in the majority of patients.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991.     

Effects of crack cocaine on neurocognitive function

Because crack cocaine appears to have a preferential effect on the metabolic and electrophysiological activity of the frontal and temporal regions of the brain (Pascual-Leone et al., 1991a, 1991b; Volkow, 1992), we hypothesized that cognitive measures of those regions would be impaired in crack cocaine users relative to measures in normal volunteers. We used logistic regression to determine the relationship of cocaine usage to neuropsychological test performance. We compared 38 patients with an average of 3.6 (SD = 2.5) years of crack cocaine use and 24.5 (SD = 28.1) days of abstinence to 54 normal volunteers on a battery of neuropsychological tests. Statistical adjustments were made for the effects of age, education, socioeconomic class, and level of depression. Our findings were mixed with regard to purported measures of executive/frontal functioning, with worse performance associated with cocaine usage on the Booklet Categories Test, but better performance associated on others (number of categories on the Wisconsin Card Sorting Test, Controlled Oral Word Association). Cocaine usage was associated with impairment on measures of spatial, but not verbal memory, confrontation naming, and Trail-making Test, Part B, a measure of perceptual-motor speed and cognitive flexibility. In summary, it appears that continuous crack cocaine use produces a dissociative pattern in neuropsychological test performance with improvement on some measures, but deterioration on others. The permanence of these effects remains to be determined with longitudinal studies.     

Quantitative immunohistochemical differences in Langerhans cells in dermatitis due to internal versus external antigen sources

Cutaneous hypersensitivity reactions can develop against antigens delivered through the epidermis (contact dermatitis) or through the blood vessels (e.g., drug eruptions). On routine histology alone, it is not always possible to determine the route of the antigen. Langerhans cells (LC) are the main antigen-presenting cells in contact dermatitis. Dermal dendrocytes (DC) are antigen-presenting cells and may be involved in dermal reactions. We tested the hypothesis that there is a difference between dermatitis due to external and internal antigen sources with regard to the number or function of LC and DC. In 85 cases of dermatitis, numhers of S100 and HLA-DR reactive cells per linear millimetre of epidermis were counted. The amount of epidermal spongiosis was evaluated qualitatively. In 35 cases, the numher of DC per mm² (as defined by Factor XIIIa expression) was evaluated. The patients were then divided into two groups based on whether the final clinical evaluation considered the dermatitis to be secondary to an external (35 cases) or internal antigen (50 cases). Dermatitis due to external antigens had significantly more LC/mm and more frequent HLA-DR expression than dermatitis due to internal antigens, mean ± SEM; 21.2±2.04 vs. 9.1±1.02 (p<0.00001) and 16.3±2.49 vs. 6.0±0.92 (p=0.0001), respectively. Spongiosis was more marked in external antigen cases. DC were more numerous in internal than in external antigen cases, but the differences were not statistically significant. In our model, determination of numbers of LC/mm is the variable with the highest power to discriminate between internal and internal sources. Quantification of HLA-DR+ LC and degree of spongiosis provide little additional discriminatory power.     

Effect of health visitors working with elderly patients in general practice: a randomised controlled trial

Health visitors were employed specifically to care for two years for a random sample of patients in general practice who were aged over 70. Independent assessments made at the beginning and end of the study showed that the health visitor in an urban practice had some impact on her caseload of patients; she provided more services for them, their mortality was reduced, and their quality of life improved, though the last measure just failed to be statistically significant. The health visitor working in a rural practice had no such effect.     

Patterns of Sinusitis in Cystic Fibrosis

It has been pediatric dogma that most children with cystic fibrosis (CF) have pansinusitis and few are symptomatic. To reassess this premise, we compared symptoms, clinical examinations, radiographic and surgical findings, and results of treatment in 19 children with cystic fibrosis who had undergone computed tomography at St. Christopher's Hospital (Philadelphia) from 1991 to 1994. We found two distinct patterns of sinus disease: chronic sinusitis (n = 3) and polyposis (n = 12). Two of the patients with polyposis had ethmoid mucoceles and 1 child had no sinus disease at all. Children with chronic sinusitis had headache as a major complaint, while those with polyposis suffered nasal obstruction alone unless a mucocele was present. Surgery provided marked and lasting improvement in the 14 patients who were operated on.