Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis.

Axon outgrowth during development and neurotransmitter release depends on exocytotic mechanisms, although what protein machinery is common to or differentiates these processes remains unclear. Here we show that the neural t-SNARE (target-membrane-associated-soluble N-ethylmaleimide fusion protein attachment protein (SNAP) receptor) SNAP-25 is not required for nerve growth or stimulus-independent neurotransmitter release, but is essential for evoked synaptic transmission at neuromuscular junctions and central synapses. These results demonstrate that the development of neurotransmission requires the recruitment of a specialized SNARE core complex to meet the demands of regulated exocytosis.     

Video-EEG Study of Psychogenic Nonepileptic Seizures: Differential Characteristics in Patients with and without Epilepsy

Summary:  Purpose: Psychogenic nonepileptic seizures (PNES) are episodes that may resemble epileptic seizures (ES) but are not associated with abnormal electrical discharges in the brain. Video-EEG recording of a typical episode is considered the best diagnostic tool available. PNES are, however, also documented in patients with epilepsy (PNES/ES). The purpose of this study was to assess this comorbid population, focusing on the differences between patients with PNES/ES and patients with PNES alone.
Methods: We reviewed 110 PNES episodes, occurring spontaneously or induced by means of suggestion techniques, recorded in our video-EEG laboratory over a period of eight years. We identified two subgroups of patients, consisting of 85 PNES cases and 25 PNES/ES cases, and assessed any differences in their characteristics by reviewing a number of variables (age, sex, clinical features, antiepileptic therapy, age of onset, time to diagnosis, pathological history, and length of follow-up).
Results: The comparison between the two subgroups revealed that PNES/ES patients displayed some statistically significant differences when compared with PNES alone patients, i.e., younger age, a higher percentage of spontaneously activated events, a shorter disease duration, a longer time to PNES diagnosis, and a lower percentage lost at follow-up.
Conclusions: This study confirms that PNES is a common, though probably underestimated, occurrence in epilepsy services. Our results shed light on some different characteristics between PNES and PNES/ES patients.     

Myxoglobulosis of the appendix

Myxoglobulosis is a rare morphologic variant of appendiceal mucocele characterized by intraluminal mucinous globules of the appendix. Most reported cases have presented clinically as an acute abdomen or as an incidental laparotomy or autopsy finding. We report a case of myxoglobulosis in a 32-year-old man who presented with an extra-appendiceal mass following a 10-year symptomatic course. Laparotomy disclosed a pericecal collection of opaque, white globules originating from a perforated appendix walled off by fibrous adhesions. The globules exhibited some histologic and staining properties at variance with those described in previous reports. These findings suggest that myxoglobulosis may be more heterogeneous pathogenetically than the distinctive gross appearance of the lesion would indicate.     

Further consideration of the clonal nature of Salmonella typhi: evaluation of molecular and clinical characteristics of strains from Indonesia and Peru.

We examined envelope protein profiles, chromosomal restriction endonuclease digest patterns, and immune responses to envelope proteins for collections of Salmonella typhi strains isolated in Peru and Indonesia. Only minor differences in envelope protein patterns were apparent among strains. Strains from 7 of 20 Indonesian patients had a distinct chromosomal digest pattern compared with patterns of Peruvian and other Indonesian strains. Strains with this pattern carried the gene for the j flagellar antigen (H1-j); differences in response to envelope proteins of j and d strains were noted on immunoblot analysis. Our data suggest that there are genotypic and phenotypic differences among S. typhi strains. The clinical importance of these differences remains to be fully evaluated; however, in this study it was not possible to show a clear correlation between strain characteristics and disease severity.     

Non invasive estimation of mean right atrial pressure utilizing the 2D-Echo transverse diameter of the left hepatic vein

Aim of our study was to assess if the 2D-Echo transverse diameter of the left hepatic vein (LHV) obtained from the subcostal approach is correlated with invasive mean right atrial pressure (RAP). Thirty-two consecutive patients with acute myocardial infarction were studied by simultaneous 2D-Echo and right heart catheterization. LHV could be adequately imaged in 90% of patients. Mean RAP values at catheterization ranged from 0 to 15mmHg (mean 6±3.5 mmHg). A correlation was found between mean RAP and LHV diameter calculated after inspiration (r=0.81, SEE=1.54 mm, slope=0.71,p< 0.001) as well as after expiration (r=0.82, SEE=1.32mm, slope=0.62,p< 0.001) or during post-expiratory apnoea (r=0.85, SEE=1.3 mm, slope=0.71,p< 0.001). Moreover, percent increments of LHV diameter correlated well with percent changes of mean RAP during rapid infusion of 250–500 cc of saline in 4 patients (r=0.98,p< 0.001). Thus, the 2D-Echo LHV diameter is a feasible measurement that seems to correlate well with invasive mean RAP over a wide range of mean RAP values in patients with myocardial infarction; the changes in LHV diameter correlate well with the percent increase in central venous pressure obtained with saline infusion. Underestimation of invasive RAP occurs when mean RAP value exceeds 12 mmHg and can be explained by limited venous compliance. However these preliminary results suggest that this method may represent a valid alternative to obtain a non invasive estimate of mean RAP with 2D-Echocardiography.     

Effect of MHC class-I transfection on local tumor growth and metastasis in an H-2-negative clone derived from a chemically induced fibrosarcoma.

GR9 is a chemically induced fibrosarcoma composed of clones with different H-2 class-I expression. These clones differ with respect to local growth and spontaneous metastasis. The B9 clone (H-2 negative) is highly tumorigenic (local growth) but of low metastatic potential (spontaneous metastasis assay). We have analyzed the effect that transfection of H-2Dd and H-2Kd genes on this clone have upon local growth, lung colonization after i.v. injection and ability to form spontaneous metastases. The results showed that the effect on local growth of transfection of the Kd-gene was stronger than that of the Dd gene. In addition, B9 co-transfected with H-2Kd and Dd genes showed the highest immunogenic properties in syngeneic BALB/c mice. Interestingly, the pSV2-neo transfected clone gave almost the same result as that obtained with Dd transfection. Lung colonization after i.v. injection of the different clones (experimental metastasis), paralleled the results obtained for local growth: the number of lung nodules followed the cadence KdDd less than Kd less than Dd less than pSV2. Survival of mice was always inversely correlated with local growth, e.g., all mice injected with 5 x 10(5) B9 H-2KdDd transfected cells survived. In contrast, no mice injected with the B9 control did. These differences were abrogated in irradiated and nude BALB/c mice. Finally, all transfected clones remained non-metastatic in a spontaneous metastasis assay, behaving as the control, non-transfected B9 cells.     

Acute and chronic ethanol alter somatosensory-evoked potentials in conscious rats.

This study examined the effects of acute and chronic ethanol on cortical somatosensory-evoked potentials (SEPs) of laboratory rats. Evoked potentials were recorded following stimulation of the left hindpaw before and after injection of either saline or ethanol. Animals were then chronically exposed to ethanol in vapor inhalation chambers for five weeks. Recordings of SEPs before and after acute ethanol injection were then obtained 24 h and again seven days after withdrawal from ethanol exposure. The results indicate that acute ethanol produced a dose-dependent reduction in SEP amplitude, but did not alter peak latencies. Chronic ethanol exposure and withdrawal resulted in a significant increase in preinjection baseline response amplitudes when measured at 24 h after withdrawal, but not at seven days, and this treatment did not alter response latency or the effects of acute ethanol administration.     

RESPONSIVENESS AND SENSITIVITY TO CHOLINERGIC AGONISTS AND ANTAGONISTS IN BOVINE ISOLATED BRONCHIAL MUSCLE

1. Airways derived from different levels of the lung exhibit a difference in the reactivity and sensitivity to agonists. We have evaluated the effect of acetylcholine and cholinergic selective (pirenzepine, gallamine and 4-dipherylacetoxymethyl piperidine [4-DAMP]) and non-selective (atropine) antagonists on bovine proximal and distal smooth muscle preparations. 2. The distal preparations are more sensitive to acetylcholine than proximal bronchi. The relaxant effect of three selective antagonists on the distal and proximal tissues was the same when the results for each drug were compared. 3. Atropine and 4-DAMP were more potent than pirenzepine and gallamine in relaxing both proximal and distal bovine smooth muscle preparations. 4. These data suggest that the muscarinic sites on the smooth muscle of bovine airways are of the M3 subtype.