Lipid components of aminoacyl-tRNA synthetase complex in eukaryotes and their function

This review includes data about lipids composition of eukariotic high molecular complex of aminoacyl-tRNA synthetases under normal conditions and under the effect of ionizing radiation. The role of different lipids in formation of the structure of high molecular complex and functioning is discussed. The role of different groups of phospholipids, prostaglandins in providing the normal work of high molecular complex and some synthetases in control and pathological state is considered. A conclusion has been made that different groups of lipids composed the high molecular complex aminoacyl-tRNA synthetases. Some of them play structural role and other (prostaglandins, some phospholipids) are the regulatory components of the complex.     

An outbreak of Candida parapsilosis prosthetic valve endocarditis

The histologic features of normal and hyperplastic epithelia of the extra-glandular excretory ducts of human minor salivary glands were studied, and their pathologic significance evaluated. Normal duct epithelium consisted of two layers: inner columnar cells, and basal cubical or squamous cells. A few goblet cells were present among the inner cells. Hyperplasia of the duct epithelia occurred focally or entirely, and was classified into the following histologic types: (1) simple hyperplasia, and (2) metaplastic hyperplasia, which were divided into (a) mucous cell hyperplasia, (b) oncocytic hyperplasia and (c) squamous cell hyperplasia. Squamous cell hyperplasia was subdivided into (i) acanthotic type and (ii) reserve cell-like type with or without dysplasia. Simple or metaplastic epithelial hyperplasia of the extra-glandular excretory ducts of minor salivary glands may be induced by chronic inflammation or other types of irritation, and proliferating cells of such regenerating tissue sometimes exhibit features reminiscent of a neoplastic process. Furthermore, it is suggested that metaplastic epithelial hyperplasia of the excretory minor salivary gland ducts could be the site of origin of tumor development, i.e., some oral squamous cell carcinomas may arise from primary lesions in the hyperplastic epithelium of the extraglandular excretory minor salivary gland ducts.     

Safety of a single aerosol administration of escalating doses of the cationic lipid GL-67/DOPE/DMPE-PEG5000 formulation to the lungs of normal volunteers

Several groups are assessing the use of cationic lipids for respiratory gene therapy. To date no human data are available regarding the safety of intra-pulmonary cationic lipid delivery. In preparation for a trial of pulmonary delivery of the CFTR gene, we have assessed the safety of nebulised lipid GL-67/DOPE/DMPE-PEG5000 (GL-67A), the cationic lipid formulation to be used in this study. Fifteen healthy volunteers were given incremental doses of GL-67A via a Pari LC Jet nebuliser; three volunteers in each of five dosing cohorts with a week interval between cohorts. Markers of safety included clinical assessment, measurement of lung function, chest CT scan, serological testing and analysis of induced sputum. Measurements were taken before administration and at intervals up to 21 days thereafter. No adverse clinical events were seen or any statistically significant changes in spirometry or gas transfer. There were no clinically significant changes in any of the blood parameters and no CT changes were seen. Comparisons of the cellular subpopulations (neutrophils, eosinophils, lymphocytes and macrophages) in induced sputum showed no significant alterations following administration of the GL-67A. This study suggests that a single application of aerosol formulation of GL-67A does not result in clinically detectable changes when given by nebulisation into the lungs of normal volunteers and provides an indication of a lipid dose tolerated in man.     

Cellular and molecular determinants of cisplatin resistance

Cisplatin and carboplatin are among the most active and widely used cytotoxic anticancer drugs. However, the acquisition or presence of resistance significantly undermines the curative potential of these drugs against many malignancies. Multiple potential mechanisms of resistance have been identified at the cellular and molecular levels. Alterations in cellular pharmacology, including decreased drug accumulation, increased cellular thiol levels and increased repair of platinum-DNA damage, have been observed in numerous model systems. More recently, it has become apparent that an enhanced capacity to tolerate cisplatin-induced damage may also contribute to resistance. Alterations in proteins that recognise cisplatin-DNA damage (mismatch repair and high-mobility group (HMG) family proteins) and in pathways that determine sensitivity to apoptosis may contribute to damage tolerance. It remains to be determined whether any of these mechanisms contribute significantly to resistance in the clinical setting. Ongoing biochemical modulation and translational correlative trials should clarify which specific mechanisms are most relevant to clinical cisplatin resistance. Such investigations have the potential to improve the ability to predict likelihood of response and should identify potential targets for pharmacological or molecular intervention.     

Effects of various handling and storage conditions on stability of Treponema pallidum DNA in cerebrospinal fluid

Treponema pallidum DNA from even small numbers of organisms was detectable in cerebrospinal fluid (CSF) stored at room temperature or at 4 degrees C for several hours and in CSF subjected to three freeze-thaw cycles. These results suggest that negative PCR results for T. pallidum from patients diagnosed with T. pallidum invasion of the central nervous system are probably not due to the loss of target DNA prior to testing.     

A prospective algorithm for the management of air leaks after pulmonary resection

BACKGROUND: Air leaks (ALs) are a common complication after pulmonary resection, yet there is no consensus on their management. METHODS: An algorithm for the management of chest tubes (CT) and ALs was applied prospectively to 101 consecutive patients who underwent elective pulmonary resection. Air leaks were graded daily as forced expiratory only, expiratory only, inspiratory only, or continuous. All CTs were kept on 20 cm of suction until postoperative day 2 and were then converted to water seal. On postoperative day 3, if both a pneumothorax and AL were present, the CT was placed to 10 cm H2O of suction. If a pneumothorax was present without an AL, the CT was returned to 20 cm H2O of suction. Air leaks that persisted after postoperative day 7 were treated with talc slurry. RESULTS: There were 101 patients (67 men); on postoperative day 1, 26 had ALs and all were expiratory only. Univariable analysis showed a low ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) (p = 0.005), increased age (p = 0.007), increased ratio of residual volume to total lung capacity (RV/TLC) (p = 0.04), increased RV (p = 0.02), and an increased functional residual capacity (FRC) (p = 0.02) to predict the presence of an AL on postoperative day 1. By postoperative day 2, 22 patients had expiratory ALs. After 12 hours of water seal, 13 of the 22 patients' ALs had stopped, and 3 more sealed by the morning of postoperative day 3. However, 2 of the 6 patients whose ALs continued experienced a pneumothorax. Five of the 6 patients with ALs on postoperative day 4 still had ALs on postoperative day 7, and all were treated by talc slurry through the CT. All ALs resolved within 24 hours after talc slurry. CONCLUSIONS: Most ALs after pulmonary resection are expiratory only. A low FEV1/FVC ratio, increased age, increased RV/TLC ratio, increased RV, and an increased FRC were predictors of having an ALs on postoperative day 1. Conversion from suction to water seal is an effective way of sealing expiratory AL, and pneumothorax is rare. If an expiratory AL does not stop by postoperative day 4 it will probably persist until postoperative day 7, and talc slurry may be an effective treatment.     

Biliary excretion of dolichols and beta-hexosaminidase--effect of ethanol and glucagon

Alcohol has been reported to increase the urinary excretion of dolichols, and urinary dolichols are suggested to be derived from the lysosomes of the renal cells. In the present study we examined the effects of alcohol and glucagon on the biliary excretion of dolichols in rats. Chronic ethanol treatment decreased both biliary dolichol and beta-hexosaminidase excretion. The absolute amount of dolichol excreted into the bile correlated highly significantly with the absolute amount of biliary beta-hexosaminidase. Our results indicate that biliary dolichols are--at least in part--derived from hepatic lysosomes. Decreased biliary dolichol output during chronic alcohol administration suggests that urinary and biliary dolichol excretions are regulated independently of each other.     

The characteristics of the spread of Coxiella burnetii in the Carpathian region

The paper presents data of the long-term (1975-1994) study of Q fever in Carpathian region [correction of Forecarpathia] (Ivano-Frankivs'k and Chernivtsi provinces) and dynamics of epidemiologic manifestations of this disease during the recent years. It is shown that after Q fever outbreaks in 1975-1977, people sick for it have been recorded sporadically, and a considerable decrease of epidemiological manifestations of Coxiella burnetii circulation is observed in the late years. This is accompanied by the decrease of the immune stratum among the population from 10.1% to 1.6-2.8%. In the authors opinion there is the interepizootic period now when the agent population remains in the phase of reservation that requires devoting much attention to the future appearance of its epidemiologically dangerous variants. The expediency of the purposeful examination of the profile therapeutic patients for Q fever and a necessity of special study of the chronic form of this infection are emphasized.     

Family health care delivery for the 21st century

The objective of this study was to investigate whether and how parotid saliva flow and composition correlated with the perception of gustatory and/or trigeminal stimuli in foods. Thirty (15 male and 15 female) subjects tasted seven foods or beverages (lemonade, beer, wine, soup, methyl cellulose, peanut butter, and crackers) with three levels each of a gustatory or trigeminal stimulus and rated the perceived intensity of the corresponding sensation over time using the time-intensity (TI) method while their parotid saliva was being collected. Salivary flow rates of males were significantly higher than those of females for all stimuli (p < 0.001). That did not translate, however, into consistent differences in perception of sensory attributes between males and females. Significant positive correlations were found between saliva flow and (1) TI parameters for adhesiveness of peanut butter and cohesiveness of mass of crackers (p < 0.05 or lower) and (2) time from intake to swallowing of crackers and peanut butter (p < 0.05). No correlations were found between saliva composition (e.g., sodium and total protein) and TI parameters. These results indicate that parotid saliva flow may correlate with the perception of some texture and mouthfeel attributes (presumably through oral work and bolus formation) but not with that of the taste attributes examined in this study (at the concentrations studied).