E-cadherin-beta-catenin adhesion complex in neuroendocrine tumors of the lung: a suggested role upon local invasion and metastasis.

Dysfunction or loss of the intercellular adhesion complex E-cadherin-beta-catenin is frequent in non-small cell lung carcinomas in which E-cadherin and beta-catenin loss has been considered to be a molecular marker of tumor progression and poor prognosis. With an aim of evaluating the expression of the E-cadherin-beta-catenin complex and its prognostic role in neuroendocrine tumors (NET) of the lung, immunohistochemical analysis was performed in 102 NET, including 16 low-grade typical carcinoids, 8 intermediate-grade atypical carcinoids, 37 large-cell neuroendocrine carcinomas (LCNEC), and 41 small-cell lung carcinomas, both high-grade tumors. Impaired E-cadherin expression (loss or cytoplasmic delocalization) was observed in 80 (78%) of 102 samples, and impaired beta-catenin expression was noted in 74 (72%) of 102 cases. The impaired expression of E-cadherin and beta-catenin was observed with a higher frequency in high-grade tumors (87% and 83%, respectively) than in carcinoids (50% and 37%, respectively; P < 0.0001). Impaired expression of the E-cadherin and beta-catenin molecules also correlated with lymph node metastasis (P = 0.0001 and P = 0.0005, respectively) and with advanced stage disease (P < 0.0001 for both factors). Moreover, impaired E-cadherin expression directly correlated with an extensive disease in carcinoids and in LCNEC (P = 0.02 and P = 0.04, respectively) and with node metastasis in LCNEC (P = 0.01). Levels of E-cadherin and beta-catenin were correlated with each other, consistent with an internal regulatory loop. Our results indicate that down-regulation of the E-cadherin-beta-catenin complex plays a role in NET progression.

24-hour (nyctohemeral) and sleep-related variations of intraocular pressure in healthy white individuals.

Intraocular pressure was measured hourly during 24 hours in 12 young (20.6 +/- 0.3 years, mean +/- SEM) and 12 older (59.5 +/- 1.6 years) healthy white adults to determine whether intraocular pressure followed a circadian rhythm and whether its nocturnal variations were related to the stages of sleep in the subjects. An electronic tonometer (Tono-Pen), working on the applanation principle, which was shown to give accurate intraocular pressure measurements in any posture, was used to measure intraocular pressure. Nocturnal polysomnography was measured. Wakefulness, light sleep (stages 1 and 2), slow-wave sleep (stages 3 and 4), and rapid eye movement sleep were scored. Intraocular pressure followed a circadian rhythm with a nocturnal peak value (acrophase). The variations in intraocular pressure were related to the stage of sleep, being lowest during rapid eye movement sleep, and highest during slow-wave sleep.

[Basedow's disease and atypical ophthalmologic signs]. / Maladie de Basedow et signes ophtalmologiques atypiques.

The authors report a case of BASEDOW's disease discovered with CT scan. The beginning was uncommon, characterized by orbital pains associated with optic neuropathy without any other signs of hyperthyroidism.

Effects of oleic acid-, alpha-naphthylthiourea-, and phorbol myristate acetate-induced microvascular damage on indexes of pulmonary endothelial function in anesthetized dogs.

To study the value of indexes of endothelial cell function in experimentally induced pulmonary microvascular injury, lung damage was produced in anesthetized dogs by intravenous injection of oleic acid (OA; n = 6), alpha-naphthylthiourea (ANTU; n = 5), or phorbol myristate acetate (PMA; n = 6). Angiotensin-converting enzyme (ACE) activity in serum and simultaneous measurements of serotonin (SER) and propranolol (PROP) pulmonary extraction along with several physiologic parameters were determined and compared with those obtained in a control group (n = 5) before and then at 2-h intervals for 8 h after administration of the toxic agent. ACE activity in serum showed a sustained and significant increase in the PMA and OA groups throughout the whole study period, whereas it decreased significantly at 4 h in the ANTU group. SER pulmonary uptake decreased significantly, but slightly, only in the PMA group at 8 h (-5%). At 6 and 8 h respectively, PROP extraction dropped significantly in the PMA (-11 and -13%) and OA (-13 and -19%) groups. This decrease in PROP extraction was likely to result from physiologic changes due to the development of pulmonary edema as suggested by the correlation between the changes in amine uptake and those affecting pulmonary artery pressure and total static respiratory compliance. The lack of effects on SER uptake by the lungs under these experimental conditions indicate that dissociation exists between metabolic dysfunction of pulmonary endothelial cells and fluid leakage.

Physiological profile during venovenous perfusion in dogs using a polypropylene membrane lung with secondary flows.

Venovenous perfusion has been conducted in 12 healthy dogs to examine carbon dioxide (CO2) transfer and haemocompatibility over 9 h during total extracorporeal CO2 removal using a microporous polypropylene membrane lung with secondary flows in the blood channel. The anaesthetized animals were maintained normocapnic by including CO2 in the inspired gases. The CO2 removal was achieved using 0.631 m2 of active membrane, at a pulsatile Reynolds number of 50, and a CO2 extraction from blood of 17.8 ml (STP) dl-1. Gas exchange remained constant during the perfusions. Several aspects of our results suggest that the haemocompatibility of a system of the kind used here is at least as favourable as that of a steady flow device using a continuous silicone rubber membrane of equivalent gas transfer capability.

Prekallikrein activation in the adult respiratory distress syndrome.

Prekallikrein is the zymogen form of plasma kallikrein, a proteolytic enzyme of the contact system of blood coagulation, fibrinolysis and kinin formation. To assess whether prekallikrein was activated in the adult respiratory distress syndrome (ARDS), we examined plasma samples from 12 critically ill patients including five individuals with ARDS. Using the ratio between functional prekallikrein and prekallikrein-kallikrein antigen as an index for prekallikrein activation, we found that prekallikrein was extensively activated in patients with ARDS, while this was significantly less in the case of critically ill patients without ARDS. Following activation of prekallikrein in plasma, kallikrein reacts with its substrates and with protease inhibitors, among which the alpha 2-glycoprotein C1-inhibitor. Thus, we examined whether C1-inhibitor of critically ill individuals was modified in a way suggesting that it had reacted with kallikrein. Such a modification was found in the five patients with ARDS, while it was not detectable in the seven patients without ARDS. This observation further confirmed the activation of prekallikrein in patients with ARDS. We suggest that plasma kallikrein-mediated reactions, which include bradykinin release and neutrophil activation, may contribute to the pathogenesis of ARDS.

Alveolar-arterial equilibration in the lung of sheep.

In order to compare the efficiency of sheep lung with that of dog, gaseous exchange in hypoxia (FIO2 0.12-0.13) with and without CO in the inspired air ( FICO 0.001) was measured in 12 sheep (mean body weight = 30.4 kg) under pentothal anesthesia and artificial ventilation. Alveolar-arterial pressure difference of O2, % venous admixture and amount of VA/Q inhomogeneity were found to be substantially larger than in dog. Steady-state pulmonary diffusing capacity estimates, computed by three different procedures were, both for O2 and for CO, about 40% smaller than in dog. The DLO2/DLCO ratios were not significantly different from those determined on dog data: thus, the presumed beneficial effect of sheep small erythrocytes on O2 transfer could not be demonstrated. Because its DLO2/MO2 ratio is lower than that of dog, sheep appears to be more adequate than dog as a model for human alveolar-arterial gas exchange.