Telomerase activation in a model of lung adenocarcinoma.

Ovine pulmonary adenocarcinoma (OPA) is a lung cancer strikingly similar to the pneumonic-type mixed invasive adenocarcinoma with a predominant bronchioloalveolar component in humans. Telomerase activity in OPA and the potential involvement of the kinase Akt in telomerase activation and regulation of cell proliferation were investigated. Lung tissues were collected from sheep with a histopathological diagnosis of OPA or controls. Epithelial cell cultures were derived in vitro from lung tissues. Telomerase activity was evaluated using the telomeric repeat amplification protocol method. Phosphorylation of Akt was detected by Western blotting. Telomerase activity was significantly higher in OPA lung tissues compared to control lung tissues. A high telomerase activity was detected in eight out of 12 (67%) primary cell cultures derived from tumours. A high level of expression of phosphorylated Akt was found in 10 out of 27 (37%) tumours, with abolition of Akt activation in response to epidermal growth factor stimulation demonstrated in primary cell cultures derived from tumours. Telomerase activation takes place in ovine pulmonary adenocarcinoma tumour cells and may be partly attributable to Akt activation. Telomerase may inhibit cellular senescence and contribute to the accumulation of tumour cells in mixed adenocarcinoma with a bronchioloalveolar component. Further work is necessary to identify alternative signalling pathways of telomerase activation in tumours.

[JSRV (jaagsiekte sheep retrovirus) and ovine pulmonary carcinoma]. / JSRV (jaagsiekte sheep retrovirus) et cancer du poumon associé chez le mouton.

JSRV (jaagsiekte sheep retrovirus) is a betaretrovirus, infecting small ruminants. This virus is responsible for the development of pulmonary adenocarcinoma, by the transformation of epithelial cells of the bronchioli and alveoli. This animal cancer is related to human bronchioloalveolar cancer (BAC), a specific form of human lung cancer for which a viral etiology has been proposed for several decades. In small ruminants JSRV interacts with the cells through the Hyal2 receptor. JSRV genome is simple and does not contain already known oncogene. It is now well established that the envelope protein is oncogenic by itself, via the cytoplasmic domain of the transmembrane glycoprotein and some domains of the surface glycoprotein. Activation of the PI3K/Akt and MAPK pathways participates to the envelope-induced transformation. The tumour development is associated with telomerase activation.

Spinal and intestinal levels of substance P, calcitonin gene-related peptide and vasoactive intestinal polypeptide following perendoscopic injection of formalin in rat colonic wall.

Acute inflammation of the colonic wall was induced by perendoscopic injection of formalin in rats. As compared to control animals (no endoscopy, no injection), the procedure was followed by a marked reduction of immunoreactive substance P, calcitonin gene-related peptide and vasoactive intestinal peptide concentrations in rectosigmoid wall. Tissue substance P concentration in the spinal cord, at the level of afferent projection, increased at the same time. The three peptides tested are thus likely to be involved in the pathophysiology of acute intestinal inflammation. In addition, substance P may play a role in the transmission of nociceptive signals from the inflamed colonic segment.

Immunocytochemical study of peptidergic structures in Brunner's glands.

Nervous and endocrine peptidergic structures in human Brunner's glands were studied by immunofluorescence. Endocrine cells storing immunoreactive components respectively similar to somatostatin 14, the amino-terminal portion (1-14) of somatostatin 28, gastrin-cholecystokinin, and peptide YY were distributed throughout the acini. Peptidergic nerve structures contained materials immunologically related to vasoactive intestinal peptide, peptide histidine methionine, substance P, neuropeptide Y, and gastrin-releasing peptide. The latter peptide was detected in discrete fibers running into the acini but within no cell body in the submucosa. All other neuropeptides were stored in fibers, isolated or grouped in bundles, and in perikarya of submucosal ganglia close to the acini. No immunoreactive structures were detected using antisera directed against pancreatic polypeptide, secretin, motilin, neurotensin, or calcitonin gene-related peptide. The results suggest that several regulatory peptides may be involved in the control of Brunner's glands in humans.

Cerebral evoked potentials after endorectal mechanical stimulation in humans.

Although numerous clinical studies have proved that impaired rectal sensation is a major factor in fecal continence dysfunctions, objective studies in this field are still lacking. To provide information on normal rectal afferents, a study of cerebral potentials evoked by mechanical stimulation of the rectal wall was carried out in 10 healthy volunteers (5 male, 5 female; age, 33-52 yr). The stimulating device consisted of a rectal balloon rhythmically inflated and deflated by means of an animal breathing ventilator. Recordings were obtained 2 cm behind the vertex (C'z, International system 10-20). The responses were averaged from 300 to 800 sweeps. The average was triggered either on inflation ("on effect") or on deflation ("off effect"). Inflation volume and pressure were adjusted to induce a clear but not painful pulsing sensation. Reproducible responses were recorded by both on and off effects. The evoked potentials were polyphasic with a succession of positive and negative waves (peak latencies between 78 and 310 ms). The shape of the response (morphology, latency, and amplitude) was perfectly reproducible in the same subject. With regard to intrasubject reproducibility, variability was displayed: only the early waves (latency less than 100 ms) were perfectly reproducible; late waves exhibited variable latency and morphology. The present findings are the first demonstration of the possibility of recording an evoked potential on the scalp after a mechanical stimulation of the rectum.

Pregnancy-induced increase of spinal cord peptide concentrations in rats.

Tissue peptide concentrations of immunoreactive vasoactive intestinal peptide, somatostatin, substance P and cholecystokinin were measured by radioimmunoassay in undivided cervical, thoracic, lumbar and sacral segments of spinal cords from female Sprague Dawley rats either non pregnant or sacrificed at day 7, 14, 21, and 22 of pregnancy. Non pregnant animals showed for all peptides significant decreasing sacro-cervical gradients of tissue concentrations. Pregnancy was associated with significant rises of immunoreactive somatostatin concentration at the sacral level, and of immunoreactive VIP in the four segments tested. Peak values were recorded between day 14 and day 21, with a brisk decrease of VIP, but not of somatostatin, concentration on day 22. Sacrocervical gradients followed a biphasic increase, reaching a maximum on day 22. The concentrations of immunoreactive substance P and cholecystokinin remained stable throughout pregnancy. The present results suggest that the somatostatinergic and VIPergic structures stored in, or projecting to, the sacral autonomic nuclei are involved in the control of the anatomical and/or physiological modifications of the female genital tract during pregnancy.

Substance P-, somatostatin-, vasoactive intestinal peptide- and cholecystokinin-like levels in the spinal cord of polyarthritic rats.

Substance P-, somatostatin-, vasoactive intestinal polypeptide- and cholecystokinin-like levels were measured in lumbar dorsal and ventral cord of polyarthritic rats and compared with those obtained in vehicle-treated rats taken as controls. Polyarthritis decreased substance P concentration in lumbar ventral cord and increased cholecystokinin level in lumbar dorsal cord, while the other two peptides did not show any change. The results are discussed in relation to immunohistochemical data found in the literature.