The concept of synergism in radiobiology]

We have demonstrated previously that pemphigus vulgaris (PV)-IgG induces activation of phospholipase C (PLC), production of inositol 1,4,5-trisphosphate, and a rapid transient increase in [Ca2+]i in cultured human keratinocytes, leading to secretion of plasminogen activator and cell-cell detachment in cell culture. In the current study, to examine the involvement of protein kinase C (PKC) in the mechanism of blister formation in PV, we studied the PV-IgG-induced translocation of PKC isozymes from the cytosol to the particulate/cytoskeleton (p/c) fractions and the activation of PKC in human keratinocytes. Cells cultured in Eagle's minimum essential medium were incubated with PV-IgGs for 30 s, 1 min, 5 min, or 30 min. PV-IgG binding to the cell surface antigen (desmoglein III) induced translocation of PKC-alpha from the cytosol to the p/c fractions within 30 s, with a peak at 1 min that lasted at least 30 min. PKC-delta also was translocated within 1 min and reached a peak at 5 min but was reduced to basal levels at 30 min. Alternatively, PKC-eta translocation to the p/c fraction was induced slowly, taking more than 5 min, and was reduced to approximately half-maximum at 30 min, whereas PKC-zeta translocation reached a maximum at 30 s, rapidly returning to baseline by 5 min after PV-IgG stimulation. The total PKC activity in the p/c fraction also was increased after PV-IgG exposure, peaked at 1 min, and was sustained for at least 30 min. These findings suggest that a unique activation profile of PKC isomers may be involved in mediating the intracellular signaling events induced by PV-IgG binding to desmoglein III in cultured human keratinocytes.     

Nutrient utilization by sheep and performance and carcass characteristics of steers fed crab waste-straw silage

Exacerbations of asthma have been associated with exposure to ozone or particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10). We postulated in this study that the association of summertime air pollution (i.e. ozone and PM10) with acute respiratory symptoms, medication use and peak expiratory flow differs among patients grouped according to asthma severity. During the summer of 1995, effects of ambient air pollution on these parameters were studied in a panel of 60 nonsmoking patients with intermittent to severe persistent asthma. These patients were recruited from our Pulmonary Out-patient Clinic. Subgroup analysis was performed on the degree of hyperresponsiveness and lung steroid use before the start of the study, as indictors for the severity of asthma. Associations of the parameters studied with ozone, PM10, nitrogen dioxide (NO2), sulphur dioxide (SO2) and black smoke were evaluated using time series analysis. Several episodes with increased summertime air pollution occurred during the 96 day study period. Eight hour average ozone concentrations exceeded the World Health Organization (WHO) Air Quality Guidelines (120 microg x m(-3)) on 16 occasions. Daily mean levels of PM10 were moderately elevated (range 16-98 microg x m(-3)). Levels of the other measured pollutants were low. There was a consistent, positive association of the prevalence of shortness of breath (maximal relative risk (RRmax) 1.18) with ozone, PM10, black smoke and NO2. In addition, bronchodilator use was associated with both ozone and PM10 levels (RRmax 1.16). Stratification by airway hyperresponsiveness and steroid use did not affect the magnitude of the observed associations. No associations with peak expiratory flow measurements were found. We conclude that the severity of asthma is not an indicator for the sensitivity to air pollution.     

Translation eukaryotic initiation factor 4G recognizes a specific structural element within the internal ribosome entry site of encephalomyocarditis virus RNA

A complex of eukaryotic initiation factors (eIFs) 4A, 4E, and 4G (collectively termed eIF4F) plays a key role in recruiting mRNAs to ribosomes during translation initiation. The site of ribosomal entry onto most mRNAs is determined by interaction of the 5'-terminal cap with eIF4E; eIFs 4A and 4G may facilitate ribosomal entry by modifying mRNA structure near the cap and by interacting with ribosome-associated factors. eIF4G recruits uncapped encephalomyocarditis virus (EMCV) mRNA to ribosomes without the involvement of eIF4E by binding directly to the approximately 450-nucleotide long EMCV internal ribosome entry site (IRES). We have used chemical and enzymatic probing to map the eIF4G binding site to a structural element within the J-K domain of the EMCV IRES that consists of an oligo(A) loop at the junction of three helices. The oligo(A) loop itself is not sufficient to form stable complexes with eIF4G since alteration of its structural context abolished its interaction with eIF4G. Addition of wild type or trans-dominant mutant forms of eIF4A to binary IRES.eIF4G complexes did not further alter the pattern of chemical/enzymatic modification of the IRES.     

Diagnosis of pancreatic carcinoma: role of FDG PET

OBJECTIVE: The purpose of this study was to investigate the role of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in differentiating benign from malignant disease in patients with possible pancreatic malignancy. SUBJECTS AND METHODS: All patients with a possible diagnosis of pancreatic carcinoma based on CT or ERCP findings were eligible for inclusion in this prospective study. PET imaging of the abdomen was performed in 37 patients and was interpreted as positive if FDG activity in the pancreas exceeded background activity and as negative if activity was less than or equal to background activity. Semiquantitative analysis was performed by calculating a standardized uptake ratio. Studies were reviewed independently by two radiologists, and results were correlated with biopsy results and with CT and ERCP findings. Sensitivity and specificity of FDG PET for revealing pancreatic malignancy was determined. RESULTS: FDG activity in the pancreas was increased in 24 patients, and adenocarcinoma was diagnosed in 22 of these patients (92%). Two patients (8%) with increased activity had benign disease, including one patient with chronic pancreatitis who showed no evidence of tumor at laparotomy and one patient with a mucinous cystic tumor who showed no malignant features at laparotomy. FDG uptake was low or normal in 13 patients, 10 of whom (77%) had benign disease. FDG uptake was also low in three patients with adenocarcinoma, whose tumor size ranged from 2 to 4 cm in diameter. The mean standardized uptake ratio value for malignant disease was 5.1 (range, 1.0-10.1) and for benign disease was 1.9 (range, 0.0-5.8) (p < .001). The sensitivity of FDG PET for revealing malignant disease in the pancreas was 88% and the specificity was 83%. CONCLUSION: FDG PET is a sensitive and specific noninvasive technique for the diagnosis of pancreatic malignancy.     

The laboratory diagnosis of spring-summer infections in Yekaterinburg in the epidemic season for tick-borne encephalitis

The authors propose a comprehensive approach to laboratory diagnosis of seasonal transmissible infections, based on modern methods permitting etiological deciphering of disease. A universal diagnostic algorithm notably accelerated the laboratory diagnosis due to cutting the period between collection of material from a patient and consecutive screening for antibodies to agents of tick-borne encephalitis, Lyme disease, and California encephalitis.     

Pulmonary function changes after nebulised and intravenous frusemide in ventilated premature infants

AIMS: To compare the effects of a single dose of frusemide administered either intravenously or by nebulisation on pulmonary mechanics in premature infants with evolving chronic lung disease. METHODS: The effect of frusemide on pulmonary mechanics was studied at a median postnatal age of 23 (range 14-52) days in 19 premature infants at 24 to 30 weeks gestational age, who had been dependent on mechanical ventilation since birth. Frusemide (1 mg/kg/body weight) was administered, in random order, intravenously and by nebulisation, on two separate occasions 24 hours apart. Pulmonary function studies were performed before and at 30, 60, and 120 minutes after administration of frusemide. Urine was collected for six hours immediately before and for six hours after administration of frusemide. RESULTS: Nebulised frusemide increased the tidal volume 31 (SE 11.5)% and compliance 34 (SE 12)% after two hours, whereas no change in either was noted for up to two hours after intravenous frusemide administration. Neither intravenous nor nebulised frusemide had any effect on airway resistance. Six hour urine output increased from a mean (SE) of 3.3 (0.4) ml/kg/hour to 5.9 (0.8) ml/kg/hour following intravenous frusemide administration while nebulised frusemide had no effect on urine output. Urinary sodium, potassium, and chloride losses were also significantly higher after intravenous frusemide, whereas nebulised frusemide did not increase urinary electrolyte losses. CONCLUSION: Single dose nebulised frusemide improves pulmonary function in premature infants with evolving chronic lung disease without adverse effects on fluid and electrolyte balance.     

Trends in registered psychiatric morbidity and forecasting psychotropic drug needs in Bulgarian hospitals

Registered psychiatric morbidity in Bulgaria as a whole and particularly in Plovdiv, the second largest region of the country, was assessed. Three aspects of psychotropic drug usage were analysed, namely, changes in registered psychotropic drugs, the prescribed daily dose (PDD) values for 2 years, and the preferred therapeutic schemes, and drug usage and needs in a psychiatric hospital with 365 beds. This was done by time series analysis for evaluation of psychiatric morbidity and drug consumption data, calculation of PDD for psychotropic medicines, and, based on a modification of the World Health Organization's morbidity method, assessment and prediction of drug use and needs in Plovdiv hospital. The results indicated that the registered morbidity had increased by 4% over the period 1989-93 to 2,427 psychiatric patients per 100,000 people. The increased consumption of especially benzodiazepines and sedative medicines was analyzed. Diazepam was prescribed the most often (91.1%), followed by levomepromazine (86.4%), haloperidol (82.7%), etc. Future drug consumption in Plovdiv hospital is expected to decrease because therapeutic practice in hospitals has been revised and improved on the basis of the World Health Organization's recommendations.     

Clinical and functional evaluation of health status of workers exposed to infrasound, noise and general vibration

The article covers complex evaluation of health state in building industry workers engaged into ferro-concrete production in St. Petersburg. The health state was considered under combined action of infrasound, noise and general vibration. Clinical and functional evaluation included medical examination by doctors, blood biochemistry and CBC, ECG, computer integral rheography, voice audiometry. Data for 62 moulders helped to assess acoustic environment at workplace and to reveal the morbidity structure.     

Influence of Neotyphodium coenophialum on copper concentration in tall fescue

Poor performance of livestock that graze tall fescue (Festuca arundinacea Schreb.) has been associated with the endophyte fungus Neotyphodium coenophialum [Morgan-Jones and Gams] Glenn, Bacon, and Hanlin). Recent evidence suggests lowered Cu status and a depression of Cu-related immune function in steers that graze endophyte-infected (E+) tall fescue. Greenhouse and field studies investigated relationships between the endophyte and Cu concentrations in tall fescue. Seventeen infected 'Kenhy' clones were divided, and one plant of each pair was treated three times with Benomyl to remove the endophyte (E-). Plants were watered with nutrient solution in a greenhouse for 6 mo before sampling. Copper concentrations were greater (P < .001) in E- than in E+ clones (3.4 vs 2.8 microg/g; SE, .06). In the second greenhouse experiment, genetically similar E+ and E- 'Kentucky'-31 (KY-31) and 'Georgia Jessup' were grown from seed and fertilized with nutrient solution to produce mature plants. Copper concentrations were higher (P < .05) in E- than in E+ tall fescue (8.6 vs 7.6 microg/g; SE, .3). In a field plot experiment in Texas, E+ and E- KY-31 were grown with 0, 50, and 100% replacement of potential evapotranspiration. By September, Cu concentrations were higher (P < .05) in E- than in E+ tall fescue (7.3 vs 6.6 microg/g; SE, .2). In pasture experiments, KY-31 E+ (> 70% infection level) and E- (< 5% infection level) tall fescue were grown in Virginia at two locations with three rates of N fertilizer. Copper concentrations were higher (P < .05) in E- than in E+ tall fescue (4.8 vs 4.5 microg/g; SE, .1) and increased (P < .01) linearly in response to N. Our data demonstrate that the presence of the endophyte is associated with lower Cu concentrations in tall fescue, which may contribute to lowered Cu status in animals and thus contribute to the etiology of fescue toxicity.