Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer's disease

The allelic frequency of the gene for the K variant of butyrylcholinesterase (BCHE-K) was 0.17 in 74 subjects with late-onset (age > 65 years) histopathologically diagnosed Alzheimer's disease (AD), which was higher than the frequencies in 104 elderly control subjects (0.09), in 14 early-onset cases of confirmed AD (0.07) and in 29 confirmed cases of other dementia (0.10). The association of BCHE-K with late-onset AD was limited to carriers of the epsilon 4 allele of the apolipoprotein E gene (APOE), among whom the presence of BCHE-K gave an odds ratio of confirmed late-onset AD of 6.9 (95% C.I. 1.65-29) in subjects > 65 years and of 12.8 (1.9-86) in subjects > 75 years. In APOE epsilon 4 carriers over 75 years, only 1/22 controls, compared with 10/24 confirmed late-onset AD cases, had BCHE-K. We suggest that BCHE-K, or a nearby gene on chromosome 3, acts in synergy with APOE epsilon 4 as a susceptibility gene for late-onset AD.      

Spontaneous reanastomosis between lymphatic vessels following syngeneic transplantation of the small intestine in the rat

Abstract Spontaneous lymphvascular reanastomosis (SLR) following small bowel transplantation in rats is of clinical relevance for the resorption of long chain fatty acids. Detailed morphological and molecular data concerning the process of lymphvascular reanastomosis are not available in the literature. In this study SLR was investigated using microradiology and scanning electron microscopy. Between the 8^th and 21^st postoperative days following transplantation SLR does not occur between the intestinal trunk of the transplant and the thoracic duct of the recipient. Instead, an indirect connection was observed between the inserted advential lymphatic vessels of the mesenteric artery and lymphatic vessels of the aorta or ductus deferens, which are connected with the thoracic duct.     

Amino acid protection of cultured kidney tubule cells against calcium ionophore-induced lethal cell injury.

Treatment of two cultured renal tubule epithelial cell lines, MDCK and LLC-PK1, with ionomycin produced rapidly evolving models of lethal cell injury characterized by increases of cytosolic free calcium to the microM level within 15 minutes followed by lactate dehydrogenase release and failure to exclude vital dyes that began between 30 and 60 minutes and became extensive after 60 minutes. The pattern of injury was similar when the mitochondrial uncoupler, carbonyl cyanide-m-chlorophenylhydrazone, was added to ionomycin. Carbonyl cyanide-m-chlorophenylhydrazone alone produced severe ATP depletion but not lactate dehydrogenase release. Inclusion of glycine in the experimental medium at concentrations ranging from 0.25 mM to 5 mM did not affect the increases of cytosolic free calcium or ATP depletion but was protective against enzyme release and failure to exclude vital dyes for 180 minutes. Maximal protection was achieved at glycine concentrations between 1 and 5 mM. Several other small neutral amino acids including alanine, beta-alanine, L-serine, 1-aminocyclopropane-1-carboxylic acid, and alpha-aminoisobutyric acid also had protective effects but, glucose, pyruvate, glutamate, glutamine, leucine, valine, and taurine did not. These data indicate that potent protective effects of glycine and other small neutral amino acids previously shown in fresh tubule preparations are fully expressed in cultured tubule cells of diverse origin when appropriate acute injury models are used and the protective effects are sustained for long durations. The suitability of cultured cell lines for prolonged exposure studies will provide a powerful way of further exploring mechanisms of these effects.     

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive,non-randomized study of cancer-free and oral squamous cell carcinoma subjects

Background  

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.     

Autoantibodies to the high-affinity IgE receptor in children with chronic urticaria.

BACKGROUND: Chronic urticaria (CU) in childhood remains a challenge for investigation, and its etiology is largely unknown. Autoantibodies to the high-affinity IgE receptor (FcepsilonRI) are believed to play a role in the pathogenesis of this disease in adults. OBJECTIVE: To determine the prevalence of autoantibodies to FcepsilonRIalpha on basophils in children with CU vs atopic eczema dermatitis syndrome (AEDS). METHODS: Eighty children with CU were compared with 38 children with AEDS. In addition to complete blood cell counts and total IgE measurements, CAP-RASTs to egg, codfish, soy, milk, and peanut were performed. Stool samples were examined for parasites, and autologous serum skin testing and a functional anti-FcepsilonRIalpha assay were conducted to detect autoantibodies. RESULTS: No significant differences were observed between children with CU and controls in mean basophil or eosinophil counts. Twenty (26%) of 77 children with CU and 31 (82%) of 38 with AEDS had positive CAP-RAST results (P < .001). Only 2.5% of the children with CU and 0% with AEDS had stool samples positive for parasites (P = .005). Anti-FcepsilonRIalpha autoantibodies were positive in 37 (47%) of 78 children with CU and in none of 33 with AEDS. Non-IgG histamine-releasing factors were found in 10 (13%) of 78 children with CU. CONCLUSIONS: Children have a similar prevalence of autoantibodies to the FcepsilonRIalpha as has been previously published for adults. Few have type I allergies, and parasite infestation is also uncommon. Further studies are required to investigate the predictive value of the autoantibodies in these children with respect to clinical profile, requirements for medications other than antihistamines, and remission rates.     

A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase A develops endocrine and other tumours: comparison with Carney complex and other PRKAR1A induced lesions

Background: Inactivation of the human type Iα regulatory subunit (RIα) of cyclic AMP dependent protein kinase (PKA) (PRKAR1A) leads to altered kinase activity, primary pigmented nodular adrenocortical disease (PPNAD), and sporadic adrenal and other tumours.

Methods and results: A transgenic mouse carrying an antisense transgene for Prkar1a exon 2 (X2AS) under the control of a tetracycline responsive promoter (the Tg(Prkar1a*x2as)1Stra, Tg(tTAhCMV)3Uh or tTA/X2AS line) developed thyroid follicular hyperplasia and adenomas, adrenocortical hyperplasia and other features reminiscent of PPNAD, including late onset weight gain, visceral adiposity, and non-dexamethasone suppressible hypercorticosteronaemia, with histiocytic, epithelial hyperplasias, lymphomas, and other mesenchymal tumours. These lesions were associated with allelic losses of the mouse chromosome 11 Prkar1a locus, an increase in total type II PKA activity, and higher RIIß protein levels; the latter biochemical and protein changes were also documented in Carney complex tumours associated with PRKAR1A inactivating mutations and chromosome 17 PRKAR1A locus changes.

Conclusion: We conclude that the tTA/X2AS mouse line with a downregulated Prkar1a gene replicates several of the findings in Carney complex patients and their affected tissues, supporting the role of RIα as a candidate tumour suppressor gene.

     

Evaluation of R-Mix shell vials for the diagnosis of viral respiratory tract infections.

Respiratory viruses cause significant morbidity and mortality. The management of these infections can be improved by a rapid diagnosis and administration of available virus-specific therapy. The goal of this study was to compare R-Mix, an engineered tissue monolayer for rapid shell vial (SV) diagnosis of viral respiratory infections, with conventional tissue culture (TC) and conventional respiratory SV (primary rhesus monkey kidney (RhMK) and Hep2 monolayers). The primary outcome measure was sensitivity for detection of influenza A and B, respiratory syncytial virus, parainfluenza 1-3, and adenovirus. The study was performed in two phases: (1) the three methods were compared using 250 nasal washes from children with lower respiratory tract infections; (2) a modified R-Mix SV harvesting schedule (SV were harvested at 24 and 120 h) was compared with TC and conventional RhMK/Hep2 SV using 311 respiratory specimens. A total of 110 viruses were identified in the first and 55 in the second phase. Diagnostic accuracies of R-Mix harvested at 24, 48, and 120 h were 98%, whereas for TC varied between 99 and 100%, and for RhMK/Hep2 SV between 98 and 99%. Sensitivities of R-Mix harvested at 24, 48, and 120 h were 26, 75, and 47%, respectively, whereas for TC varied between 60 and 94%, and for RhMK/Hep2 SV between 62 and 85%. R-Mix harvested at 48 h represent a valuable substitute for RhMK/Hep2 SV because they have comparable sensitivities and diagnostic accuracies, but R-Mix offers several technical advantages. In contrast, R-Mix harvested at 24h did not seem a very useful diagnostic tool. The utility of R-Mix harvested at 120 h, which accelerated the diagnosis of 16% of positive specimens in study phase 2, needs further investigation.