Behavioral inhibition system (BIS), behavioral activation system (BAS) and schizophrenia: relationship with psychopathology and physiology.

OBJECTIVE: The Behavioral Inhibition System (BIS) and the Behavioral Activation System (BAS) have been conceptualized as two neural motivational systems that regulate sensitivity to punishment (BIS) and reward (BAS). Imbalance in BIS and BAS levels has been reported to be related to various forms of psychopathology. Since sensitivity to stress has been supposed to be a pathway for the development of psychotic symptoms, the aim of this study is to examine BIS and BAS scores in schizophrenia and their relationship with psychopathology and physiology. METHOD: Forty-two patients with schizophrenia (26 men, 16 women), stable on atypical antipsychotics, and 37 healthy controls (17 men, 20 women) were assessed with the use of the Behavioral Inhibition and Behavioral Activation scales. Since increased average heart rate (HR) and decreased heart rate variability (HRV) have been reported in patients with schizophrenia and have been shown to correlate with inhibited behaviour, these psychophysiological measures were also obtained. The BIS/BAS data and HR/HRV data were both analyzed by a (M)ANOVA. Correlation coefficients were computed for associations between BIS/BAS data, HR/HRV data, and patient variables. RESULTS: On the BIS, patients showed higher sensitivity to threat than control subjects. Higher BIS sensitivity correlated with longer duration of illness, and lower negative symptoms on the PANSS. The BAS scores did not reveal differences between patients and controls. In patients, low BAS sensitivity correlated with low dosage of medication. On the physiological measures patients showed a significantly higher HR and lower HRV compared to controls, which was limited to clozapine treated patients. No correlations were found between HR/HRV scores and BIS/BAS scores or patient variables. CONCLUSIONS: Male as well as female patients with schizophrenia are more sensitive to threat than healthy controls. This may reflect a trait-related characteristic, and is not reflected in state-related psychophysiological measures.

Schizophrenia and processing of facial emotions: sex matters.

The aim of this study was to examine sex differences in emotion processing in patients with schizophrenia and control subjects. To this end, 53 patients with schizophrenia (28 men and 25 women), and 42 controls (21 men and 21 women) were assessed with the use of a facial affect recognition morphing task. Accuracy and sensitivity scores were measured. Women performed better than men in labelling negative emotions. On the same task, patients performed worse than control subjects, irrespective of sex, although the largest degree of impairment was seen in male patients. In conclusion, emotion perception was disproportionally affected in men with schizophrenia relative to women. This may explain, in part, why women with schizophrenia are less impaired in social life than men suffering from this illness.

How should we measure blood pressure in the doctor's office?

BACKGROUND: Blood pressure is the most ubiquitous diagnostic recording made in the doctor's office, but the measurement is subject to a number of sources of bias, which may lead to over- or underestimation. The current study examined the systematic influence of the way in which the measurements were taken - by the physician, by a nurse, or with the patient sitting alone, using an automated device. SUBJECTS AND METHODS: Blood pressure was measured in 17 essential hypertensive and 10 white-coat hypertensive individuals. On separate clinic visits, measurements were taken by the attending physician, by a nurse and using an automated device (Arteriosonde 1216). RESULTS: A repeated-measures ANOVA revealed that, for systolic pressure, there was a significant effect of measurement modality on blood pressure. Physician systolic pressures were on average approximately 10 mmHg higher than those taken by a nurse, nurse pressures being approximately 7 mmHg higher than those recorded using Arteriosonde. The effect on diastolic pressure was similar but smaller, and no nurse-Arteriosonde difference was observed. CONCLUSIONS: We conclude that the routine clinical assessment of blood pressure would be more representative of daily ambulatory pressure if an automated device, without doctor or nurse present, were used.

Protein synthesis shut-off induced by influenza virus infection is independent of PKR activity.

The role of PKR activity in influenza virus-induced cell shut-off was studied by infection of PKR(+) or PKR(-) cell cultures and metabolic labeling in vivo. No differences in the synthesis of viral proteins or the decay of cellular protein synthesis were observed. To investigate the relevance of the inhibition of cellular pre-mRNA polyadenylation and nucleocytoplasmic transport in virus-induced shut-off, we carried out similar experiments with mutant viruses lacking C-terminal sequences of NS1 protein. No differences in the shut-off induced by mutant versus wild-type viruses were observed, indicating that these nuclear events are not relevant for shut-off. The analysis of cytoplasmic mRNA stability indicated that the accumulation of viral mRNA during the infection correlated with the progressive decay of cellular mRNA, in both the wild type and an NS1 deletion mutant.

Interaction of influenza virus NS1 protein and the human homologue of Staufen in vivo and in vitro.

A screening for human proteins capable of interacting with influenza virus NS1 has been carried out using the two-hybrid genetic trap in yeast. A cDNA corresponding to the human homologue of Drosophila melanogaster Staufen protein (hStaufen) was isolated that fulfilled all genetic controls of the two-hybrid protocol. Using a hStaufen cDNA isolated from a lambda human library, the interaction of hStaufen and NS1 proteins was characterised in vivo and in vitro. Co-transfection of NS1 cDNA and a partial cDNA of hStaufen led to the relocalisation of recombinant hStaufen protein from its normal accumulation site in the cytoplasm to the nuclear location of NS1 protein. NS1 and hStaufen proteins could be co-immunoprecipitated from extracts of co-transfected cells and from mixtures of extracts containing either protein, as well as from extracts of influenza virus-infected cells. Furthermore, both proteins co-localised in the ribosomal and polysomal fractions of influenza virus-infected cells. The interaction was also detected in pull-down experiments using a resin containing purified hStaufen and NS1 protein translated in vitro. Deletion mapping of the NS1 gene indicated that a mutant protein containing the N-terminal 81 amino acids is unable to interact with hStaufen, in spite of retaining full RNA-binding capacity. These results are discussed in relation to the possible mechanisms of action of hStaufen and its relevance for influenza virus infection.

A human sequence homologue of Staufen is an RNA-binding protein that is associated with polysomes and localizes to the rough endoplasmic reticulum.

In the course of a two-hybrid screen with the NS1 protein of influenza virus, a human clone capable of coding for a protein with high homology to the Staufen protein from Drosophila melanogaster (dmStaufen) was identified. With these sequences used as a probe, cDNAs were isolated from a lambda cDNA library. The encoded protein (hStaufen-like) contained four double-stranded RNA (dsRNA)-binding domains with 55% similarity and 38% identity to those of dmStaufen, including identity at all residues involved in RNA binding. A recombinant protein containing all dsRNA-binding domains was expressed in Escherichia coli as a His-tagged polypeptide. It showed dsRNA binding activity in vitro, with an apparent Kd of 10(-9) M. Using a specific antibody, we detected in human cells a major form of the hStaufen-like protein with an apparent molecular mass of 60 to 65 kDa. The intracellular localization of hStaufen-like protein was investigated by immunofluorescence using a series of markers for the cell compartments. Colocalization was observed with the rough endoplasmic reticulum but not with endosomes, cytoskeleton, or Golgi apparatus. Furthermore, sedimentation analyses indicated that hStaufen-like protein associates with polysomes. These results are discussed in relation to the possible functions of the protein.

The mammalian staufen protein localizes to the somatodendritic domain of cultured hippocampal neurons: implications for its involvement in mRNA transport.

In hippocampal neurons, certain mRNAs have been found in dendrites (), and their localization and translation have been implicated in synaptic plasticity (). One attractive candidate to achieve transport of mRNAs into dendrites is Staufen (Stau), a double-stranded RNA-binding protein, which plays a pivotal role in mRNA transport, localization, and translation in Drosophila (). Using antibodies raised against a peptide located in the RNA-binding domain IIa and a polyclonal antibody raised against a recently cloned human Staufen homolog, we identify a 65 kDa rat homolog in cultured rat hippocampal neurons. In agreement with the exclusive somatodendritic localization of mRNAs in these cells, we find that Staufen is restricted to the same domain. By immunoelectron microscopy, we show enrichment of the mammalian homolog of Stau (mStau) in the vicinity of smooth endoplasmic reticulum and microtubules near synaptic contacts. Finally, the association of the mStau with neuronal mRNAs is suggested by the colocalization with ribonucleoprotein particles specifically in distal dendrites known to contain mRNA, ribosomes, and translation factors (). These results suggest a role for mStau in the polarized transport and localization of mRNAs in mammalian neurons.

The N-terminal half of the influenza virus NS1 protein is sufficient for nuclear retention of mRNA and enhancement of viral mRNA translation.

A collection of C-terminal deletion mutants of the influenza A virus NS1 gene has been used to define the regions of the NS1 protein involved in its functionality. Immunofluorescence analyses showed that the NS1 protein sequences downstream from position 81 are not required for nuclear transport. The capacity of these mutants to bind RNA was studied by in vitro binding tests using a model vRNA probe. These experiments showed that the N-terminal 81 amino acids of NS1 protein are sufficient for RNA binding activity. The collection of mutants also served to map the NS1 sequences required for nuclear retention of mRNA and for stimulation of viral mRNA translation, using the NP gene as reporter. The results obtained indicated that the N-terminal 113 amino acids of NS1 protein are sufficient for nuclear retention of mRNA and stimulation of viral mRNA translation. The possibility that this region of the protein may be sufficient for virus viability is discussed in relation to the sequences of NS1 genes of field isolates and to the phenotype of known viral mutants affected in the NS1 gene.

Influenza virus NS1 protein interacts with viral transcription-replication complexes in vivo.

The interaction of influenza virus NS1 protein with other viral products in the infected cell was analysed by co-immunoprecipitation studies. The three subunits of the polymerase and the nucleoprotein, but not M1 protein, were co-immunoprecipitated by NS1-specific serum but not when control serum was used. Such co-immunoprecipitation was not sensitive to RNase treatment of the immunoprecipitates. Co-immunoprecipitation was also obtained when the viral transcription-replication system was reconstituted in vivo by transfection of cDNAs and model vRNA template into vaccinia virus-T7-infected cells. Analysis of the RNA pulled-down in the NS1-specific precipitates indicated the presence of both vRNA and mRNA. These results are discussed in the context of the phenotype of virus temperature-sensitive mutants affected in the NS1 gene.

What is the value of home blood pressure measurement in patients with mild hypertension?

To investigate the value of home blood pressure (BP) measurements, the BP was recorded daily by the patient at home and compared with recordings in the physician's office and with a 24-hour BP recording taken with a noninvasive ambulatory BP recorder in a group of 93 patients with mild untreated hypertension. Office BPs (mean 148/94 mm Hg) were higher than either home (138/89 mm Hg) or average 24-hour BPs (131/89 mm Hg). For systolic BP, home and office measurements gave similar correlations with 24-hour BP (0.67 and 0.55). For diastolic BP, however, home readings were lower and more accurate (0.76 vs 0.36). Thus, our findings indicate that home readings reflect the overall level of BP more reliably than office readings, and if due consideration is given to the fact that they are usually lower than office readings, they may be used as an alternative and cost-effective means of evaluating patients with mild hypertension.

Long-term efficacy of captopril in renovascular and essential hypertension.

Captopril was used in primary and long-term treatment of 40 treatment-resistant hypertensive patients. Of these, 21 had renovascular hypertension, seven unilateral and fourteen bilateral, and 19 had essential hypertension, 10 with high-renin and 9 with normal-renin profiles. All patients were off treatment when started on captopril therapy and were treated for at least 12 months, on the average for more than 2 years. The strategy of systematic drug withdrawal used to find the lowest effective dose of captopril led to average doses of 150 to 300 mg/day. A diuretic agent was added in 17 of the 40 patients when diastolic pressure remained greater than 105 mm Hg and a beta-adrenergic blocking agent was added for tachycardia or additional pressure control in 16 patients. Captopril alone was effective in 14 of the 40 patients. In all groups, mean supine and standing blood pressure levels were maintained at less than 140/90 mm Hg without evidence of decreased effectiveness over time. Control and treatment systolic pressures were higher in patients older than 50 years. For patients of all ages, systolic but not diastolic pressure during captopril treatment was higher in the supine position than standing. Plasma renin activity remained significantly elevated over time and aldosterone excretion usually decreased despite concurrent diuretic therapy. Captopril alone or in combination with a diuretic or beta-adrenergic blocking agent is effective in long-term treatment of drug-resistant renovascular and essential hypertension.