CD8+ T cells in intracellular bacterial infections of mice

In the normal course of an immune response, both CD4+ and CD8+ T cells respond to each of the bacterial pathogens we have discussed and both responses may be required for the most potent immunity to infection. In this discussion, we have focused on the ability of these organisms to prime CD8+ T-cell responses in vivo and the ability of CD8+ T cells as sole mediators of acquired immunity, to protect against infection. It is clear that the vacuolar location of bacterial pathogens such as Salmonella or Mycobacteria does not prevent in vivo priming of CD8+ T-cell responses to these pathogens. However, vacuolar localization may affect the potency of CD8+ T-cell responses under experimental conditions that assess the capacity of CD8+ T cells as the sole mediators of acquired immunity. In the case of cytoplasmic L. monocytogenes, clear evidence exists that antigen-specific CD8+ T cells, in the absence of immune CD4+ T cells, can provide substantial acquired immunity to naive mice. Similar clear experimental results with Salmonella and Mycobacteria are lacking. Such results would provide stronger support for vaccines that elicit CD8+ T-cell responses to these vacuolar pathogens. Although our discussion has focused on only three specific organisms, we suggest that detection of an in vivo CD8+ T-cell response to a bacterial antigen does not ensure that the response will be protective against infection in a vaccine setting. In the case of Salmonella and Mycobacteria, this issue remains unresolved.     

Predictability of early atopy by cord blood-IgE and parental history

BACKGROUND: Atopic family history and cord blood IgE have been used as predictors of atopic disease in newborns for about 20 years, but at least for cord blood IgE the sensitivity has been shown to be very low. The objective of this paper was to evaluate whether parental history and cord blood-IgE were more accurate predictors for the appropriate atopic phenotypes in the infants rather than for any atopy. METHODS: A total of 1314 newborn infants was recruited in six German obstetric departments in 1990 and followed-up for 2 years. Four hundred and ninety-nine (38%) were at high risk for atopy with at least two first degree atopic family members and/or elevated cord-blood IgE concentrations. RESULTS: The cumulative incidence of atopic dermatitis over the first 2 years of life (AD24) amounted to 20.1%, and there was a significant association with AD history of the mother (OR 2.5, 95%CI 1.46-4.26) and of the father (OR 3.53, 95%CI 1.90-6.54). The cumulative incidence of recurrent wheezing in the first 2 years of life (RW24) amounted to 16.1%, and was positively associated with asthma history (OR 2.11, 95%CI 1.33-3.60) and sensitization history (OR 1.64, 95%CI 1.34-2.36) of the mother, but with neither for the father. RW24 was less prevalent in girls than in boys (OR 0.64, 95%CI 0.47-0.89). Thirty-one per cent of infants were sensitized (CAP test value > 0.35 kU/L) against at least one of nine food or inhalative allergens (S24) and this was significantly associated with cord blood-IgE value (OR 2.43, 95%CI 1.69-3.49), and sensitization history of the mother (OR 1.64, 95%CI 1.18-2.41). Using multiple logistic regression analysis, the prediction of AD24 by AD of parents, of RW24 by asthma of parents, and of sensitization by cord blood IgE was of low accuracy. CONCLUSION: The predictive capacity of parental history and cord blood IgE is not high enough to recommend them as screening instruments for primary prevention. The majority of atopic manifestations and of sensitization occur in infants with no demonstrable risk at birth.     

The relationship between compositional phase separation and vesicle morphology: implications for the regulation of phospholipase A2 by membrane structure

The action of phospholipase A2 (PLA2) on bilayer substrates causes the accumulation of reaction products, lyso-phospholipid and fatty acid. These reaction products and the phospholipid substrate generate compositional heterogeneities and then apparently phase separate when a critical mole fraction of reaction product accumulates in the membrane. This putative phase separation drives an abrupt morphologic rearrangement of the vesicle, which may be in turn responsible for modulating the activity of PLA2. Here we examine the thermotropic properties of the phase-separated lipid system formed upon hydrating colyophilized reaction products (1:1 palmitic acid:1-palmitoyl-2-lyso-phosphatidylcholine) and substrate, dipalmitoylphosphatidylcholine. The mixture forms structures which are not canonical spherical vesicles and appear to be disks in the gel-state. The main gel-liquid transition of these structures is hysteretic. This hysteresis is apparent using several techniques, each selected for its sensitivity to different aspects of a lipid aggregate's structure. The thermotropic hysteresis reflects the coupling between phase separation and changes in vesicle morphology.     

Initial-phase optimization for bioremediation of munition compound-contaminated soils

We examined the bioremediation of soils contaminated with the munition compounds 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine, and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetraazocine by a procedure that produced anaerobic conditions in the soils and promoted the biodegradation of nitroaromatic contaminants. This procedure consisted of flooding the soils with 50 mM phosphate buffer, adding starch as a supplemental carbon substrate, and incubating under static conditions. Aerobic heterotrophs, present naturally in the soil or added as an inoculum, quickly removed the oxygen from the static cultures, creating anaerobic conditions. Removal of parent TNT molecules from the soil cultures by the strictly anaerobic microflora occurred within 4 days. The reduced intermediates formed from TNT and hexahydro-1,3,5-trinitro-1,3,5-triazine were removed from the cultures within 24 days, completing the first stage of remediation. The procedure was effective over a range of incubation temperatures, 20 to 37 degrees C, and was improved when 25 mM ammonium was added to cultures buffered with 50 mM potassium phosphate. Ammonium phosphate buffer (50 mM), however, completely inhibited TNT reduction. The optimal pH for the first stage of remediation was between 6.5 and 7.0. When soils were incubated under aerobic conditions or under anaerobic conditions at alkaline pHs, the TNT biodegradation intermediates polymerized. Polymerization was not observed at neutral to slightly acidic pHs under anaerobic conditions. Completion of the first stage of remediation of munition compound-contaminated soils resulted in aqueous supernatants that contained no munition residues or aminoaromatic compounds.     

The regulation of calcitriol by parathyroid hormone and absorbed dietary phosphorus in subjects with moderate chronic renal failure

The two best-recognized stimuli for calcitriol production are parathyroid hormone (PTH) and dietary phosphorus deprivation. We studied the relative importance of these two stimuli in subjects with moderate chronic renal failure (MCRF). We recruited 10 subjects with MCRF aged 49 +/- 13 years (mean +/- SD) and having a creatinine clearance rate of 31 +/- 24 mL/min. After an overnight fast, they received 400 IU human PTH 1-34 subcutaneously, and blood and urine samples were collected over the subsequent 24 hours. They then took aluminum hydroxide 30 mmol/d for 2 months to reduce gut phosphorus absorption, at the end of which the PTH stimulation test was repeated. Responses were compared with those obtained in 11 normal subjects aged 44 +/- 16 years and having a creatinine clearance rate of 102 +/- 37 mL/min who were only studied while on their normal diet. Following PTH stimulation in the normal subjects but not the MCRF subjects, there was a significant increase in plasma calcium and calcitriol levels, with a significant decrease in renal phosphorus threshold. In both groups there was a similar and significant increase in urine cyclic adenosine monophosphate (cAMP) levels. Following restriction of absorption of dietary phosphorus in MCRF subjects, plasma calcitriol levels increased compared with baseline values. This study shows that these MCRF subjects were unable to respond with an increase in calcitriol to a PTH stimulus that produced a similar urine cAMP response in normal subjects. However, they were capable of responding to a reduction in phosphorus absorption with an increase in calcitriol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Time after feeding and dietary arginine deficiency alter splanchnic and hepatic amino acid flux in rats

The effect of an arginine-deficient diet containing 3.4% glutamate on net flux of amino acids across the portal-drained viscera and liver was studied in rats at 0, 1 or 2 h after a meal and compared with that in arginine-fed controls. Net portal-drained viscera flux for most amino acids was greater in the fed state compared with the postabsorptive state except for glycine and cystine, which did not change, and methionine, which declined. Net amino acid recovery in portal blood 2 h after feeding compared with amounts consumed was highest for alanine (17.3%); recovery of other amino acids ranged from 5.6 to 15.3%. No net portal-drained viscera recovery of consumed cystine was observed. For the branched-chain and aromatic amino acids, methionine, threonine, histidine and lysine, net hepatic uptake was nearly equal to net portal-drained viscera absorption (range 77-127% of portal-drained viscera flux). Correlation coefficients between net hepatic and portal-drained viscera fluxes for leucine, valine, isoleucine, methionine and phenylalanine were 0.84 to 0.93. Postabsorptive hepatic extraction for most amino acids was zero, but after a meal, ranged from 13.3 to 22.9% for the branched-chain and aromatic amino acids. Net hepatic production of ornithine and proline occurred in arginine-fed control rats. This value was near zero for ornithine in rats fed the arginine-deficient diet. Models of interorgan amino acid metabolism in the food-deprived and fed state are presented.     

Ambulatory monitoring of tremor and other movements before and after thalamotomy: a new quantitative technique

Tremor, e.g. in Parkinson patients, often shows large spontaneous fluctuations in severity over the day, to such an extent that a short observation is usually not sufficient to assess the overall severity or the effect of a treatment. Since momentary impressions of the tremor can thus be misleading, long-term ambulatory recordings would be helpful in the evaluation of severity and treatment effectiveness. As existing methods for long-term tremor registration have several shortcomings, a new method is proposed: an algorithm was designed to discriminate tremor from other movements and to describe the amount (i.e. the proportion of tremor or movements per time unit) as well as the intensity (i.e. average acceleration amplitude) of the two types of movement. In the evaluation of the severity of tremor both the amount and intensity of tremor episodes are of importance. The algorithm was tested on 24-h analog tape recordings of wrist-movement in 10 young and 10 aged controls, as well as in 8 patients with tremor--both before and after a tremor relieving thalamotomy. The algorithm scored movements as 'tremor' exclusively in patients prior to the operation. Fluctuations in tremor severity over the day were detected, and tremor could be discriminated from non-pathological movements. Moreover, following thalamotomy, motor slowing (bradykinesia) was detectable using this algorithm. Based on these test results, a miniaturized device in wrist-watch format is now being developed for long-term registrations.     

Key issues in the treatment of chronic lymphocytic leukaemia (CLL)

The outcome of the treatment of chronic lymphocytic leukaemia (CLL) has improved little over the past 30 years. The recent introduction of purine analogues, particularly fludarabine, may change this situation. These agents are highly effective and generally well tolerated. They raise the possibility of improved disease-free survival and allow appropriate patients to be considered for bone marrow transplantation (BMT). Randomised clinical trials are needed to establish the roles of purine analogues and other novel agents in improving the survival of CLL patients. These trials should use consistent diagnostic and assessment criteria to allow for the clinical heterogeneity of CLL.     

Si/SiGe heterojunction bipolar transistor with base doping highly exceeding emitter doping concentration

A Si/Si/sub 0.8/Ge/sub 0.2/ heterojunction bipolar transistor was fabricated having emitter, base and collector contacts at the wafer surface. The base doping concentration amounted to 10/sup 19//cm/sup 3/ which was 20 times the emitter concentration. Due to the pronounced difference in bandgap energy a current gain of 17 was reached.<>