A novel role of ImmE7 in the autoregulatory expression of the ColE7 operon and identification of possible RNase active sites in the crystal structure of dimeric ImmE7

Site-specific cleavage of mRNA has been identified in vivo for the polycistronic colicin E7 operon (ColE7), which occurs between G and A nucleotides located at the Asp52 codon (GAT) of the immunity gene (ceiE7). In vitro, this specific cleavage occurs only in the presence of the ceiE7 gene product (ImmE7). The crystal structure of dimeric ImmE7 has been determined at 1.8 A resolution by X-ray crystallographic analysis. We found that several residues located at the interface of dimeric ImmE7 bear surprising resemblance to the active sites of some RNases. These results suggest that dimeric ImmE7 may possess a novel RNase activity that cleaves its own mRNA at a specific site and thus autoregulates translational expression of the downstream celE7 gene as well as degradation of the upstream ceaE7 mRNA.     

Increased prevalence of hypertension and long-term arsenic exposure

A possible role of endothelin (ET)-1 in mediating hypoxic pulmonary vasoconstriction (HPV) was examined by comparing haemodynamic differences between ET-1-induced vasoconstriction and HPV in isolated perfused rat lungs. An ETA receptor antagonist (BQ123) was also employed to assess the effects of ET-1. The pulmonary arterial pressure (Ppa) was significantly increased by alveolar hypoxia (3% O2) and by ET-1 (5 nM). The pulmonary microvascular pressure was not changed by hypoxia, but increased more than two-fold by ET-1 (P < 0.01). Hypoxia significantly increased pulmonary arterial resistance (P < 0.01) while ET-1 significantly increased pulmonary venous resistance (P < 0.01), and slightly increased arterial resistance. Lung weight was increased by ET-1 and decreased by hypoxia, accompanied by similar Ppa responses in both cases. BQ123 (10(-6) M and 10(-5) M) did not influence the changes in Ppa and lung weight induced by hypoxia or angiotensin II (0.3 micrograms). BQ123 did, however, suppress (P < 0.05) the increase in Ppa and lung weight induced by 5 nM ET-1. Thus, it appears unlikely that ET-1 is involved in changes in pulmonary vascular tone during acute HPV.     

Acute alcohol blocks neurosteroid modulation of synaptic transmission and long-term potentiation in the rat hippocampal slice

Effects of ethanol (22 mM) on the modulation of synaptic transmission and long-term potentiation (LTP) by the neurosteroid dehydroepiandrosterone sulfate (DHEAS; 10 microM) was examined in the in vitro rat hippocampal slice preparation. The synaptic responses were elicited by Schaffer collateral stimulation and recorded extracellularly in the somatic and dendritic regions of CA1 pyramidal neurons. LTP induction produced an increase (approximately 55% to 75%) in the amplitude of synaptic responses in ethanol and ethanol plus DHEAS (ethanol/DHEAS) treated slices. These increases were significantly smaller than the approximately 130% increase observed previously in slices treated with DHEAS, but were not significantly different from the approximately 82% increase observed in control slices. These results indicate that an ethanol/DHEAS interaction prevents the enhancement of LTP normally observed with DHEAS treatment of hippocampal slices. An ethanol/DHEAS interaction also altered DHEAS's effects on individual synaptic components of the synaptic response to Schaffer collateral stimulation. Ethanol applied before but not after DHEAS prevented DHEAS's enhancement of the NMDA receptor-mediated synaptic component. DHEAS's depression of the GABAA receptor-mediated synaptic component was also blocked by ethanol. Ethanol or DHEAS individually had no effect on the AMPA receptor-mediated synaptic component, but application of ethanol after DHEAS resulted in a small enhancement of this synaptic component, an effect that was not observed if ethanol was applied before DHEAS. These results show that ethanol and DHEAS interact, altering DHEAS's effects on synaptic transmission and LTP in the hippocampus. Such an interaction may be involved in ethanol's actions on the CNS and raises the possibility that ethanol and DHEAS may act via a common site or pathway.     

Comparison of antihypertensive effects of nicardipine with nitroglycerin for perioperative hypertension

BACKGROUND: To compare the efficacy of intravenous (iv) nicardipine with nitroglycerin for the treatment for patients with perioperative hypertension. METHODS: Forty patients with perioperative hypertension randomly divided into two groups were treated with intravenous calcium entry blocker, nicardipine, or vasodilator, nitroglycerin. Haemodynamic measurements including mean arterial and pulmonary arterial pressure, central venous and pulmonary capillary wedge pressure, and cardiac output were recorded; peripheral and pulmonary vascular resistance were calculated. RESULTS: Both medications were effective in reducing blood pressure and controlling haemodynamics. During the maintenance by continuous iv infusion, nicardipine controlled hypertension more rapidly than nitroglycerin (nicardipine 10.5 +/- 2.5 min and nitroglycerin 18.7 +/- 2.8 min, p < 0.05) without significant alteration in heart rate. The total frequency of dose adjustments required to achieve therapeutic response was significantly less in the nicardipine-treated group (2.5 +/- 0.3 for nicardipine and 6.2 +/- 1.4 for nitroglycerin, p < 0.05). Incidence of hypotensive episodes during the infusion were observed in both groups [nicardipine 5% (1/20) and nitroglycerin 30% (6/20), p < 0.05]. CONCLUSIONS: Intravenous nicardipine is as effective as nitroglycerin in the treatment of perioperative hypertension. Specific advantages have been identified such as stable dose-response effect, less hypotensive and tachycardial effects during the use of iv nicardipine in treatment of hypertensive patients.     

The use of multiple antigenic peptide (MAP) in the immunodiagnosis of human immunodeficiency virus infection

In order to develop an ELISA system for the antibody detection of HIV-1 or HIV-2 infections, MAPs for HIV-1 gp41(584-618) and HIV-2 gp36(574-602) corresponding to the immunodominant regions of HIV-1 gp41 and HIV-2 gp36 were used as coating antigens in the ELISA. The MAPs were synthesized by the solid phase method using Fmoc-Lys(Fmoc)-OH and their molecular weights were confirmed by tricine gel electrophoresis. The MAPs reacted with all HIV positive sera (64 samples), but did not react with HIV negative sera (48 samples) obtained from healthy blood donors. The MAPs showed high sensitivity and specificity in anti-HIV 1/2 combo panel and anti-HIV-1 seroconversion panels. The results indicated that the ELISA system using synthetic MAPs of gp41(584-618) and gp36(574-602) as coating antigens can be used as an analytical system for the immunodiagnosis of HIV-1 or HIV-2 infections.