S-laminin and N-acetylgalactosamine located at the synaptic basal lamina of skeletal muscle are involved in synaptic recognition by growing neurites

Summary The purpose of the work reported here is to identify molecular components of the synaptic basal lamina of skeletal muscle fibres which allow recognition of original synaptic sites by regenerating motor axons. We focused on s-larninin and components recognized by the lectinDolichos biflorus agglutinin previously shown to be specifically located at the synaptic basal lamina. We used a cryoculture bioassay in which chick ciliary ganglion neurons grow on rat skeletal muscle cryostat sections. In control cultures, neurites extended over the muscle sections in close association with the muscle cell surface. It was observed that most of the neurites that extended towards the endplate zone and reached an area of 40 m around the neuromuscular junction ceased to grow when they contacted the synaptic site. Masking either lectin receptors or some s-laminin molecule epitopes prior to the culture of neurons alters the behaviour of growing neurites. On sections treated either withDolichos biflorus agglutinin or anti s-laminin monoclonal antibodies (D5 and C4) most of the neurites did not stop their growth at the synaptic regions. Moreover, treating muscle sections withDolichos biflorus agglutinin removed the gradient of substratum affinity around the endplate. These results indicate that the s-laminin andDolichos biflorus agglutinin receptors present on muscle cell surfaces may play a functional role in the interaction of growing neurites with original synaptic sites in the process of neuromuscular regeneration.     

Acute Toxicity, Toxicokinetics, and Tissue Target of Lead and Uranium in the Clam Corbicula fluminea and the Worm Eisenia fetida: Comparison with the Fish Brachydanio rerio

The general objective of our work was to propose new reference material for chemical toxicity testing and new sentinel organisms for environmental quality survey programs (freshwater or soils). We also wanted to provide basic toxicological data on the environmental effects of uranium. Thus, we conducted a comparative study to establish the acute toxicity and toxicokinetics of lead (Pb) and uranium (U) to the bivalve mollusc Corbicula fluminea and the terrestrial annelid Eisenia fetida andrei and to compare these findings with those of the well-known teleost fish Brachydanio rerio. We then measured the concentration of these metals in various tissues of the clam and the worm after two periods of exposure (4 and 11 days) to identify the affinities of these tissues for Pb and U. Our results have shown that Pb and U are very toxic to Eisenia and relatively nontoxic to Corbicula. By comparison, Pb was relatively nontoxic and U appeared to be very toxic to the fish. The toxicokinetic studies indicated that the three species are able to accumulate Pb and U, the rate and level of accumulation depending both on the species and the metal. We also found that fish and clams depurate the two metals. Data collected for the worm were conflicting: Pb was not depurated whereas tissue concentrations of U declined after the eighth day of exposure. Our study has also shown that the tissue distribution of Pb in the mollusc and in the earthworm differs significantly from that of U, both after 4 and 11 days exposure. In conclusion, these three species showed potential as bioindicators of environmental contamination by metals. Indeed, they could be used in conjunction to test different compartments of an ecosystem: worms for soils, fish for the water column, and clams for the water/sediment interface. Received: 30 October 1996/Accepted: 1 September 1998     

Distribution of p75 and trk-neurotrophin receptor proteins in adult human sympathetic ganglia

We investigated the expression of immunoreactivity (IR) for low- (p75) and high-affinity (trk proteins) neurotrophin-receptor proteins in adult human paravertebral-sympathetic ganglion neurons. Mouse monoclonal antibodies against the pan-neurotrophin-receptor p75, and rabbit polyclonal antibodies against specific epitopes of the intracytoplasmic domain on trk neurotrophin-receptor proteins were used in fresh unfixed and formaldehyde-fixed paraffin-embedded sympathetic ganglia. All adult human paravertebral-sympathetic neurons displayed trkA neurotrophin-receptor-like protein IR, 10% express trkC neurotrophin-receptor-like protein IR, 37–44% show p75 IR, and no IR was obtained for trkB neurotrophin-receptor-like protein. The intensity of immunostaining was independent of the neuron size. Labelling of non-neuronal tissues, especially blood-vessel walls, was observed for p75, trkA and trkC neurotrophin-receptor proteins. These results indicate that overlapping exists in the expression of p75 and trk neurotrophin-receptor proteins in adult human paravertebral-sympathetic neurons, and suggest that neurotrophins might act on these neurons.     

Effects of selective phosphodiesterase inhibitors on platelet-activating factor- and antigen-induced airway hyperreactivity, eosinophil accumulation, and microvascular leakage in guinea pigs

There is currently interest in the potential use of selective inhibitors of cyclic nucleotide phosphodiesterases (PDE) in the treatment of asthma. In this study we examined the effects of three selective PDE inhibitors, milrinone (PDE III), rolipram (PDE IV) and zaprinast (PDE V), on the broncoconstriction produced by antigen and histamine, the airway hyperreactivity and microvascular leakage after aerosol exposure to platelet-activating factor (PAF) and antigen, and the antigen-induced eosinophil infiltration in guinea-pig lung. Inhaled rolipram (0.01–10 mg ml^–1) inhibited dose dependently the bronchospasm produced by aerosol antigen (5 mg ml^–1) an anaesthetised, ventilated guinea-pigs. Rolipram (10 mg ml^–1) produced maximal inhibition of antigen-induced bronchoconstriction but only partial inhibition of the response to aerosol histamine (1 mg ml^–1). Milrinone and zaprinast (each 10 mg ml^–1) showed weak, or no, inhibitory effects against bronchoconstriction produced by aerosol antigen or histamine. Pretreatment with rolipram (10 mg kg^–1, i.p.) prevented airway hyperreactivity to histamine which develops 24 h after exposure of conscious guinea-pigs to aerosol PAF (500 g ml^–1) or antigen (5 mg ml^–1). The pulmonary eosinophil infiltration obtained with 24 h of antigen-exposure was inhibited by rolipram. In contrast, milrinone and zaprinast (each 10 mg kg^–1, i.p.) failed to reduce either the airway hyperreactivity of the eosinophil accumulation in these animals. Rolipram (1–10 mg ml^–1) reduced the extravasation of Evans blue after aerosol PAF (500 g ml^–1) at all airway levels while a lower dose (0.1 mg ml^–1) was only effective at intrapulmonary airways. Rolipram (0.01–1 mg ml^–1) markedly reduced airway extravasation produced by inhaled antigen (5 mg ml^–1). Zaprinast (1–10 mg ml^–1) was also effective against airway microvascular leakage produced by aerosol PAF or antigen while milrinone (10 mg ml^–1) had no antiexudative effect. These data support previous suggestions that pharmacological inhibition of PDE IV results in anti-spasmogenic and anti-inflammatory effects in the airways and may be useful in the treatment of asthma.     

Progressive acquired lymphangioma: report of a case and review of the literature

We present 2-year-old patient with a allopecia lesions in scalp, and clinique diagnostic of Cutis Aplasia. The anatomopathologic study have diagnosed the lesions as Acquired Progressive Lymphangioma (APL). Is a rare vascular tumour that has a tendency to appear in childhood an to progress slowly over the years. It could present as a solitary erythematous macule or plaque and a simple excision is usually curative. Our patient is the youngest reported in the literature.     

Phase I/II trial of irinotecan plus high-dose 5-fluorouracil (TTD regimen) as first-line chemotherapy in advanced colorectal cancer.

BACKGROUND: We conducted a phase I/II study of weekly irinotecan [30 min intravenous (i.v.) infusion] combined with 5-fluorouracil (5-FU 3 g/m(2) weekly 48 h i.v. infusion, TTD regimen) as first-line chemotherapy for patients with advanced colorectal cancer (CRC). PATIENTS AND METHODS: The maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) in the treatment of gastrointestinal solid tumors (in phase I), and the antitumor activity and toxicity of the recommended phase I dose (in phase II) were determined. RESULTS: Diarrhea was the DLT, and irinotecan 80 mg/m(2) plus 5-FU 3 g/m(2) was the recommended phase I dose. In phase II, the confirmed response rate was 44% [95% confidence interval (CI) 29% to 59%] and the median overall survival was 23.8 months. However, grade 3/4 diarrhea affected 59% of patients and led to withdrawal of three patients. A second cohort of patients studied using the same schedule but with a reduced 5-FU starting dose of 2.25 g/m(2) showed improved tolerance (the incidence of grade 4 diarrhea decreased from 28% to 11% and overall grade 3/4 diarrhea to 56%, with no patient withdrawals) but the confirmed response rate was 28% (95% CI 14% to 45%) and median overall survival was 17.2 months. CONCLUSIONS: We found weekly irinotecan 80 mg/m(2) plus TTD regimen (5-FU 2.25 g/m(2) given as 48-h i.v. infusion) to be a feasible and active combined chemotherapy for the first-line treatment of advanced colorectal cancer.