Coeliac disease, adenocarcinoma of jejunum and in situ squamous carcinoma of oesophagus

The development of both adenocarcinoma of the jejunum and in situ squamous carcinoma of the oesophagus in an adult coeliac patient is described. Good evidence that adenocarcinoma of jejunum occurs more frequently in patients with coeliac disease has recently become available though this association has been suggested for some time. While oesophageal carcinoma has long been associated with coeliac disease, in situ carcinoma of oesophagus has not been previously described in these circumstances. We feel that the risk of this complication, as calculated from published series, warrants a screening programme for oesophageal malignancy in adult coeliacs.     

An in vitro and in vivo study of the effect of incorporation of chlorhexidine into autopolymerizing acrylic resin plates upon the growth of Candida albicans

Chlorhexidine acetate was incorporated into autopolymerizing acrylic resin and, after studying its ability to diffuse out in vitro, an investigation was made into the potential of the mixture to treat palatal candidosis in the rat. Chlorhexidine was found to diffuse out of acrylic in fungicidal concentrations for up to three weeks when mixed with the acrylic powder in the proportion of 7.5% (w/w). At this concentration it was found that palatal candidosis as produced by the technique of Shakir et al. was cured or prevented. However, rats fitted with chlorhexidine supplemented plates were found not to take sufficient food during the experimental period to maintain their body weight.     

Analysis and gene assignment of mRNAs of a paramyxovirus, simian virus 5

Polypeptides synthesized by the paramyxovirus SV5 in infected CV-1 cells were readily identified when the host cell was treated with actinomycin D. The unglycosylated forms of HN and Fo synthesized in infected cells in the presence of tunicamycin and HN and Fo synthesized in vitro were identified by immunoprecipitation with specific antibodies. Separation of SV5-specific poly(A)-containing RNAs on methyl-mercury agarose gels and in vitro translation of fractions, indicated that the viral polypeptides were translated from individual mRNAs except P (Mr approximately 44K) and the nonstructural polypeptide V (Mr approximately 24K) for which the mRNAs could not be separated. cDNA copies of SV5-specific mRNAs were synthesized and cloned in plasmid pBR322. Clones to NP, P + V, M, F, and HN were identified by hybrid-arrest and hybrid-selection translation of SV5 mRNAs. Tryptic peptide mapping of polypeptides P and V indicated that the peptides of V were a subset of those of P. Hybridization of cDNA probes to infected cell mRNAs separated on agarose gels permitted identification of the NP, P + V, M, F, and HN mRNAs and presumptive polycistronic mRNAs. The sizes and sequence homologies of these polycistronic mRNAs were used to derive a likely gene order on the SV5 50 S genome RNA.     

Inositol lipid metabolism in human T lymphocytes activated via the T3 complex.

Cloned human T lymphocytes and a mitogenic monoclonal antibody (UCHT1) that binds to the T3 antigen complex were used to study the role of inositol lipid hydrolysis in T-cell activation. Binding of the T3 molecular complex with anti-T3 antibody induced the generation of inositol trisphosphate after a lag of 1 min. While this is commensurate with the rise in cytosolic Ca2+ in these cells, examination of the inositol lipid revealed that phosphorylation of phosphatidylinositol 4-phosphate to phosphatidylinositol 4,5-bisphosphate occurred before the generation of inositol trisphosphate. Thus, activation of an inositol lipid kinase appears to be one of the primary signals in cellular activation in human T lymphocytes.     

Mutations of the GREAT gene cause cryptorchidism

In humans, failure of testicular descent (cryptorchidism) is one of the most frequent congenital malformations, affecting 1-3% of newborn boys. The clinical consequences of this abnormality are infertility in adulthood and a significantly increased risk of testicular malignancy. Recently, we described a mouse transgene insertional mutation, crsp, causing high intraabdominal cryptorchidism in homozygous males. A candidate gene Great (G-protein-coupled receptor affecting testis descent), was identified within the transgene integration site. Great encodes a seven-transmembrane receptor with a close similarity to the glycoprotein hormone receptors. The Great gene is highly expressed in the gubernaculum, the ligament that controls testicular movement during development, and therefore may be responsible for mediating hormonal signals that affect testicular descent. Here we show that genetic targeting of the Great gene in mice causes infertile bilateral intraabdominal cryptorchidism. The mutant gubernaculae fail to differentiate, indicating that the Great gene controls their development. Mutation screening of the human GREAT gene was performed using DHPLC analysis of the genomic DNA from 60 cryptorchid patients. Nucleotide variations in GREAT cDNA were found in both the patient and the control populations. A unique missense mutation (T222P) in the ectodomain of the GREAT receptor was identified in one of the patients. This mutant receptor fails to respond to ligand stimulation, implicating the GREAT gene in the etiology in some cases of cryptorchidism in humans.     

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.      

A 50-kDa membrane protein mediates sialic acid-independent binding and infection of conjunctival cells by adenovirus type 37

The ocular tropism of adenovirus type 37 (Ad37) does not correlate with the wide distribution of the 46-kDa coxsackievirus and adenovirus receptor (CAR), the major receptor for most adenovirus serotypes. We previously found that Ad37 infects and binds well to conjunctival cells (Chang C), but poorly to lung epithelial (A549) cells that express CAR and hypothesized that this serotype uses a distinct receptor that is selectively expressed on conjunctival cells. To test this, we produced particles of a fiber-deleted Ad5 vector containing the Ad37 fiber protein. The "pseudotyped" vector infected Chang C cells better than A549 cells using a CAR-independent pathway. Ad37 binding was calcium-dependent and was abolished by protease digestion of cell surface proteins. Using a virus overlay protein blot assay (VOPBA), we detected calcium-dependent Ad37 binding to 50- and 60-kDa membrane proteins on permissive Chang C cells. In contrast, calcium-dependent binding was detected with only the 60-kDa protein on nonpermissive A549 cells. Ad19p, a closely related serotype that failed to bind to conjunctival cells, recognized the 60-kDa, but not the 50-kDa, protein. Ad37 has been reported to use sialic acid instead of CAR as a cell receptor on A549 cells. Pretreatment of Chang C cells with neuraminidase abolished Ad37 binding to only the 60-kDa protein, suggesting that sialic acid mediates Ad37 binding to the 60-kDa protein. The pseudotyped Ad37 vector was also able to infect neuraminidase-treated Chang C cells. Thus, subgroup D adenoviral binding to the 50-kDa protein is calcium-dependent and cell type- and serotype-specific, whereas binding to the 60-kDa protein is not necessary for infection of conjunctival cells. Together, these data suggest that the 50-kDa protein is the major receptor for Ad37 on conjunctival cells.