Identification of T cell stimulatory epitopes from the 18 kDa protein of Mycobacterium leprae

We have used different mouse strains to examine in vivo andin vitro responses to the 18 kDa protein of Mycobacterium leprae,which appears to be strongly immunogenic in both mice and humans.B and T cell stimulatory epitopes recognised by different strainsof mice have been mapped using overlapping peptides that spanthe entire 18 kDa protein. Previous work established that Immunizationof mice with the 18 kDa protein results in specific antibodyproduction to common B cell epitopes and immunization of micewith peptides containing these B cell epitopes resulted in theinduction of specific IgG to only a limited subset of epitopesin each strain. Now we report that T cells purified from miceimmunized with peptides that stimulate antibody production,proliferate in vitro when rechallenged. The proliferating Tcells produce levels of IL-2 and IFN-, that indicate antigen-specificT helper type 1 cells are present in significant numbers. Thus,a comparison of in vivo and in vitro data suggests that T cellsbearing the phenotype associated with potentially protectivecell-mediated responses can be primed in vivo by epitopes onsmall peptides. Since T cells from both strains of mice arecapable of responding to the immunogenic synthetic peptidesin vitro, but give different responses to the same peptidesin vivo, factors other than epltope structure appear to influenceT cell subset activation. This may have important implicationsfor diseases such as leprosy where a polarized T cell responseappears to develop and for the development of synthetic subunitvaccines.     

Bacteriology of Hemodialysis Fluids: Are Current Methodologies Meaningful?

Reports of increasing endotoxic reactions in dialysis centers using high-flux dialyzers and high contamination in liquid bicarbonate concentrates have resulted in concern for the microbial contamination of dialysate. The influence of salt-supplemented media on the recovery of bacterial contaminants from the fluids used in hemodialysis has been examined. This study found a negative influence of a 2% NaCl supplementation of growth media for both purified water and dialysate. Salt-supplemented pour plate cultures of bicarbonate concentrate samples were not statistically different from nonsupplemented cultures (p = 0.2). The influence of the bicarbonate salt on recovery in the pour plates was not addressed. The different media recommended for monitoring microbial contamination of dialysis fluids were compared. As previously reported, both water and dialysate collected from a relatively large geographic area showed higher recoveries on Reasoner's R2A agar than on media recommended by the Association for Advancement of Medical Instrumentation (AAMI) standards (p < 0.0001). Standard methods agar (SMA) and trypticase soy agar (TSA) produced the next highest recovery for water and dialysate, respectively. The higher recoveries generally observed on R2A or SMA suggest that to provide better patient safety these media should be selected for monitoring bacterial contamination of water, and R2A, SMA, or TSA for dialysate. The variability in the species identified across the three fluids and variability in counts observed in the different fluids suggest that significant dialysate contamination may occur from sources other than the water and bicarbonate concentrates.     

Cortical inflammation in Alzheimer disease but not dementia with Lewy bodies

BACKGROUND: There have been no previous studies on the role of inflammation in the brain for the second most common dementing disorder, dementia with Lewy bodies. OBJECTIVE: To investigate the degree of cortical inflammation in dementia with Lewy bodies (DLB) compared with Alzheimer disease (AD) and control brains. DESIGN AND MAIN OUTCOME MEASURES: Post-mortem tissue collection from a brain donor program using standardized diagnostic criteria. Brains collected from January 1, 1993, through December 31, 1996, were screened and selected only for the presence or absence of tau neuritic plaques. Results of immunohistochemistry for HLA-DR were quantified using area fraction counts. Counts were performed by investigators who were unaware of the diagnosis. Results were compared across groups using analysis of variance and posthoc testing. SETTING: A medical research institute in Sydney, Australia. PATIENTS: Eight brains with DLB and without the tau neuritic plaques typical of AD, 10 brains with AD and no Lewy bodies, and 11 nondemented controls without significant neuropathological features were selected from a consecutive sample. RESULTS: Compared with AD, DLB demonstrated significantly less inflammation in the form of HLA-DR-reactive microglia in all cortical regions (P<.001, posthoc). The level of inflammation in DLB was comparable to that seen in controls (P=.54, post hoc). CONCLUSIONS: Inflammation appears related to the tau neuritic plaques of AD. Despite similar clinical presentations, therapeutic anti-inflammatory strategies are not likely to be effective for pure DLB. Arch Neurol. 2000.     

13Carbon mixed triglyceride breath test and pancreatic enzyme supplementation in cystic fibrosis

Children with cystic fibrosis have variable degrees of exocrine pancreatic insufficiency which, if untreated, is the main cause of fat malabsorption. The impact of pancreatic enzyme supplementation on fat digestion was measured in 41 children with cystic fibrosis, 11 healthy controls, and five children with mucosal diseases by a non-invasive test of intraluminal lipolysis using 13carbon (13C) labelled mixed triglyceride (1,3-distearyl, 2[13C] octanoyl glycerol). The children with cystic fibrosis without pancreatic supplements had a median (range) 13C cumulative percentage dose recovered over six hours (cPDR) of 3.1% (0-31.7), the controls 31.0% (21.8-41.1), and the subjects with mucosal disease 27.8% (19.7-32.5). In 23 subjects with cystic fibrosis the usual dose of pancreatic enzyme supplements increased the cPDR to a median of 23.9% (0-45.6), and twice the usual dose of enteric coated microspheres increased the cPDR to 31.1% (11.1-47.8). There was no significant difference between the median cPDR of normal controls and children with mucosal disease, but there was a highly significant difference between these groups and children with untreated cystic fibrosis. Thirteen children with cystic fibrosis had no 13C recovery in their breath without enzymes and 10 showed marked increases with regular enzymes. In eight children doubling the dose of enzymes caused no or minimal improvement. The mixed triglyceride breath test offers a simple, non-invasive way of assessing the need for pancreatic enzyme supplementation in children with cystic fibrosis and could be used to optimise treatment.     

Comparison of recoveries in breath carbon dioxide of H13CO-3 and H14CO-3 administered simultaneously by single 6 h constant unprimed intravenous infusion

The aim of this study was to assess the bioequivalence of H13CO-3 and H14CO-3, by administering both labels simultaneously by single infusion and comparing their recovery in breath CO2 and urinary urea. Six healthy male subjects (age range 24-41 years; weight 76.7 (sd, 18.6) kg; height 1.79 (sd 0.05) m) were infused with unprimed solutions of HCO3- (110.0 mmol/kg) labelled with 13C (0.76 mmol 13C/h) and 14C (48 Bq/h) at a constant rate for 6 h, in a whole-body calorimeter (1400 litres) for measurement of CO2 production. Samples of breath were collected hourly in a Douglas bag and all urine was collected into two batches (0-4 h and 4-6 h) for estimating recovery of infused label by measurement of enrichment or specific activity. Recovery in breath CO2 of both labels increased from about 25 % for the first hour to 88 % and above for hours 3-4 onwards. Mean recovery of 13C in breath CO2 was slightly higher than that of 14C for all periods (mean difference always less than 1 % of infused label) but was significant only for the first 3 h (P < 0.05). Recovery of 14C in urea was significantly higher (P < 0.01) than 13C, but was confounded by substantial variability and uncertainties concerning 13CO2 background enrichments. These results suggest that there is no compelling need to alter factors currently used for recovery of 14C in breath when using 13C instead, and vice versa.     

Disentangling the Overlap between Tourette's Disorder and ADHD

Objective : To identify similarities and differences in neuropsychiatric correlates in children with Tourette's syndrome (TS) and those with ADHD. Method : The sample consisted of children with Tourette's syndrome with ADHD( N = 79), children with Tourette's syndrome without ADHD ( N = 18), children with ADHD ( N = 563), psychiatrically referred children ( N = 212), and healthy controls ( N = 140). Results: Disorders specifically associated with Tourette's syndrome were obsessive compulsive disorder (OCD) and simple phobias. Rates of other disorders, including other disruptive behavioral, mood, and anxiety disorders, neuropsychologic correlates, and social and school functioning were indistinguishable in children with Tourette's and ADHD. However, children with Tourette's syndrome plus ADHD had more additional comorbid disorders overall and lower psychosocial function than children with ADHD. Conclusions: These findings confirm previously noted associations between Tourette's syndrome and OCD but suggest that disruptive behavioral, mood, and anxiety disorders as well as cognitive dysfunctions may be accounted for by comorbidity with ADHD. However, Tourette's syndrome plus ADHD appears to be a more severe condition than ADHD alone.     

Does gut atresia cause polyhydramnios?

Fetal gut atresia is variably associated with polyhydramnios. In order to determine which pregnancies will develop polyhydramnios, the case notes of 80 babies with gut atresia and stenosis were reviewed. Maternal polyhydramnios developed in all cases of pure oesophageal atresia (n=8), all cases of Type III duodenal atresia (DA) with a non-bifid bile duct (n=8), 80% of cases with type I DA (n=10), and 24% of atresias of the small intestine (n=34). Polyhydramnios did not develop in any case where there was not total obstruction except in 1 baby with DA and a bifid bile duct (BBD). These included stenosis of the oesophagus and duodenum (n=17) and DA type III with a BBD (n=3). These results support the role of fetal swallowing and fluid absorption by the fetal gastro-intestinal tract in the regulation of amniotic fluid volume. Accepted: 24 February 1997