Truncation mutants define and locate cytoplasmic barriers to lateral mobility of membrane glycoproteins.

The lateral mobility of cell membrane glycoproteins is often restricted by dynamic barriers. These barriers have been detected by measurements of fluorescence photobleaching and recovery (FPR) and barrier-free path (BFP). To define the location and properties of the barriers, we compared the lateral mobility, measured by FPR and BFP, of wild-type class I major histocompatibility complex (MHC) membrane glycoproteins with the lateral mobility of mutant class I MHC glycoproteins truncated in their cytoplasmic domains. Mutants with 0 or 4 residues in the cytoplasmic domain were as mobile as lipid-anchored class I MHC molecules, molecules whose lateral mobility is relatively unrestricted by barriers. In contrast, mobility of class I MHC molecules with 7-residue cytoplasmic domains was as restricted as mobility of class I molecules with full-length, 31-residue cytoplasmic domains. Though some of the difference between the mobilities of mutants with 4- or 0-residue domains and the other class I molecules may be due to differences in the net charge of the cytoplasmic domain, FPR measurements of the mobility of molecules with 7-residue domains show that length of the cytoplasmic domain has an important influence on the lateral mobility. Model calculations suggest that the barriers to lateral mobility are 2-3 nm below the membrane bilayer.     

The "Melancholia Rating Scale": a useful instrument for the assessment of affective disorders. Validity and reliability of the Spanish adaptation

This instrument has been constructed with the purpose of quantifying the severity of depressive states, i.e. to identify the depressive patient and to measure the response to treatment with an antidepressant. Type of instrument: Ordinal rating scale, 11 items, 5 grades. Eleven variables are assessed: Activity (motor); Activity (verbal); Retardation (intellectual); Anxiety (psychic); Suicidal impulses; Lowered mood; Self-depreciation and guilt feelings; Emotional retardation; Sleep disturbances; Tiredness and pain; Work and interests. Tests were done to verify concurrent validity with the Hamilton Depression Scale (HDS); some data on inter-observer reliability are given.     

Common bile duct pressure in patients with common bile duct stones with or without acute suppurative cholangitis

Resting common bile duct pressure was measured in three groups of patients: group 1, 53 patients with gallstones but without common duct stones; group 2, 35 patients with common bile duct stones unaccompanied by cholangitis; and group 3, 36 patients with common duct stones and acute suppurative cholangitis. A significantly higher pressure in the common bile duct was documented in patients with cholangitis when compared with the other two groups. Twenty-four patients with cholangitis had common duct pressure values above 20 cm H2O, the maximal values of normal. Additionally, patients with cholangitis with pressure values over 30 cm H2O (nine patients) showed absence of green bile in the extrahepatic biliary tract, suggesting cessation of bile excretion into biliary duct. In all these cases, an impacted stone at the distal end of the common bile duct was documented.     

Ictal chronology and interictal spikes predict perfusion patterns in temporal lobe epilepsy: a multivariate study.

Typical (TPP) and atypical (APP) perfusion patterns (PP) may be seen in ictal SPECT of patients with temporal lobe epilepsy (TLE). APP may pose problem in the lateralization of the epileptogenic zone (EZ). We aimed to investigate predictive variables for the occurrence of TPP and APP. Fifty-one TLE patients were submitted to successful anterior-mesial temporal lobectomy. Univariate (UVA) and multivariate (MVA) analysis were performed upon clinical data, distribution of interictal spikes, and ictal chronology of seizures. From MVA, a final predictive model (FPM) was determined to better predict TPP and APP. Forty patients showed TPP (78.5%) and 11 patients APP (21.5%). Accuracy of ictal SPECT was higher in the unilateral (UIS) than in the bilateral (BIS) interictal spikes group (P = 0.05). FPM showed that patients exhibiting BIS, with shorter proportion of the electrographic seizure occurring after completion of tracer injection, and longer clinical than EEG seizure duration had more APP (P = 0.003). Generalized tonic-clonic seizures did not result in more APP. We concluded that analysis of ictal SPECT in TLE requires the knowledge of TPP and APP, the distribution of interictal spikes on temporal lobes and the ictal chronology of seizures. BIS showed that beyond a more complex epileptogenicity and seizure propagation, they may also lead to APP.     

Effects of acute hypovolaemia by furosemide on tracheal transepithelial potential difference and mucus in dogs.

Furosemide is a potent diuretic that affects water transfer across the respiratory epithelium, which is closely related to the transepithelial potential difference (PD). Water is a critical factor that determines mucus transport; an important lung defence mechanism that removes particles and microorganisms from the respiratory system. The aim of the present study was to investigate the acute effects of furosemide and hypovolaemia on tracheal PD and mucus properties. A total of 36 male mixed-breed dogs were submitted to anaesthesia, mechanical ventilation and haemodynamic monitoring. They were randomly assigned to three groups consisting of: a control group, a furosemide (40 mg i.v.) + hypovolaemia group, and a furosemide (40 mg i.v.) + volume replacement group. Tracheal PD and mucus samples were collected at time 0, 1 and 2 h after intervention. Mucus properties were analysed by means of a magnetic microrheometer and in vitro mucociliary transportability on the frog palate. Compared to controls, furosemide decreased PD to intermediate values, and only significantly when associated with hypovolaemia (-13+/-5 and -8+/-2 mV, time 0 and 2 h, respectively). In addition to the direct effect of furosemide, these results indicate that hypovolaemia also affects ion transport in the tracheal membrane. Furosemide and hypovolemia have no acute effects on respiratory mucus properties.     

Effects of midazolam on T-cell immunosuppressive response to surgical stress in mice.

Mice submitted to surgical stress induced by laparotomy and treated with chronic midazolam (1 mg/kg) showed a reduction in stress-induced suppression of thymus and spleen cellularity and in peripheral lymphocyte population. The blastogenic response of spleen lymphoid cells was also assessed and midazolam was found to partially attenuate the suppressive effect of surgery.     

Lack of control of liver gluconeogenesis in cholestatic rats with reduced portal blood flow.

Previous studies indicated a role for ischemia in the metabolic changes induced by cholestasis. Liver pyruvate kinase is a key enzyme for the concurrent control of glycolysis and gluconeogenesis. In this experiment the control of pyruvate kinase activity was investigated in cholestatic rats. Pyruvate kinase kinetics changed from a sigmoidal type in sham-operated rats to a hyperbolic type in obstructed rats. The change in the enzymatic kinetics paralleled the reduction in the portal blood flow, which reached 50% of the control value 7 days after obstruction. Dibutyryl cyclic AMP (5 mumol/kg body wt) plus theophylline 0.1 mmol/L failed to inactivate the enzyme when injected into the portal veins of rats whose livers were obstructed 7 days before. Both the kinetics changes and the lack of phosphorylation control are compatible with ischemia.