p53 Protein expression in laryngeal squamous cell carcinomas bearing wild-type and mutated p53 gene

We performed an immunohistochemical analysis to investigate the expression of p53 protein in a panel of 18 laryngeal squamous cell carcinomas, 15 primary tumours and three in relapse, previously analysed by us for the presence of p53 gene mutations. Dysplastic and/or normal surrounding mucosa was evaluated in 15 different tumours. The results of our study are the following: (1) expression of p53 protein was observed in one out of five tumours positive for p53 gene mutations (20%) and in 10 out of 13 (80%) negative cases; (2), p53 protein over-expression was frequently observed in normal and/or dysplastic mucosa surrounding either wild-type (7/11) or mutated p53 tumours (2/4); (3), p53 immunoreactive cells showed a pattern of distribution in normal and mildly/moderately dysplastic mucosa (basal layers), different from that in severely dysplastic mucosa (whole thickness). These data further support the hypothesis that p53 protein over-expression may be a marker of the earliest phases of multistep tumorigenesis in laryngeal squamous cell carcinoma.     

Doppler ultrasound evaluation of acute effects of cigarette smoking on portal blood flow in man

The acute systemic haemodynamic effects of cigarette smoking are well known, but there are no studies dealing with the possible smoke-related acute changes of splanchnic circulation in man. In the present study we evaluated the acute effects of cigarette smoking on portal blood flow (PBF) in normal subjects by the use of Doppler ultrasound. Twenty-three normal volunteers were asked to smoke two cigarettes with a known total nicotine content (1.1 mg each) in a supine position. Each cigarette was smoked during a 5 min period and a 5 min interval between the two cigarettes was allowed. Both mean PBF velocity and volume were evaluated at time 0 (basal values) and 8, 15, 30, 45 and 60 min after the first inhalation of the first cigarette. The basal mean PBF velocity (22 cm/s; 95% CI 20.9–24.2) was significantly decreased at 8 min (19 cm/s; 95% CI 17.9–20.8; P< 0.0007) and 15 min (20 cm/s; 95% CI 17.8–21.3; P< 0.005). Similarly, the PBF volumes at 8 min (710 mL/min; 95% CI 660–876; P< 0.002) and 15 min (750 mL/min; 95% CI 650–862; P< 0.005) were significantly lower than those measured at time 0 (850 mL/min; 95% CI 766–987). Both mean PBF velocity and volume measured at successive times did not differ significantly from basal values. The present study shows that cigarette smoking causes acute and transient reduction of PBF velocity and volume in normal subjects.     

Regulation of cell cyclic AMP in medullary thick ascending limb of Henle in a rat model of chronic renal failure

Chronic renal failure (CRF) is accompanied by adaptive changes in electrolyte reabsorption in the thick ascending limb of Henle of surviving nephrons. To study the cellular mechanism of this adaptation, we measured intracellular cAMP in micro-dissected medullary thick ascending limb (mTAL) segments in rats with CRF. mTAL exhibited in CRF an increase of basal cAMP from 25.6 ± 10.0 in controls to 65.8 ± 11.3 fmol mm^?1 tubule in CRF (P < 0.05). Vasopressin and calcitonin stimulated mTAL adenylate-cyclase in a dose-dependent manner in controls but failed to stimulate in CRF. Likewise, maximal stimulation with 10^?3 M 3-isobutyl-1-methylxanthine (IBMX) plus 10^?5 M forskolin increased cAMP in controls to 63.0 ± 16.0 but not in CRF, where maximal stimulated values remained at 63.1 ± 18.8 fmol mm^?1 tubule (P NS). Alpha₂-adrenoreceptor activation with clonidine at concentrations ranging from 10^?8 to 10^?6 M diminished cAMP production by 37% in CRF (P < 0.05), whereas no differences were found in controls. Thus, the basal intracellular cAMP is increased in rat mTAL in CRF. The finding that neither forskolin nor vasopressin were able to further augment intracellular cAMP would suggest that stimulatory pathways of the adenylate-cyclase system are activated in the basal state. However, mTAL cells in CRF seem to retain the response of normal epithelium to inhibitory pathways such as the one mediated by alpha₂-adrenoreceptors.