Restorative treatment need assessment by dentally and nondentally trained subjects

A study was carried out which compared how two groups of people, one with clinical dental experience and one without, assessed restorative dental treatment need. Using a visual analogue scale, a group of final year dental students ( n = 50) and nonclinical university students ( n = 50) assessed the extent to which they considered common dental imperfections, viz. spacing of the upper anterior teeth and discolouration of upper anterior teeth, warranted restorative correction. The group of dental students judged the necessity for treatment of discolouration to be more urgent than correction of spacing. The nondental group did not differentiate between the degrees of need. Data were non‐normal in distribution but the use of appropriate statistical tests showed the differences in mean assessments to be significant.     

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.     

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.     

Breast cancer risk associated with ovulation-stimulating drugs

BACKGROUND: Despite the recognized role of hormones in the aetiology of breast cancer, there has been little evaluation of hormonal preparations used to treat infertility. METHODS: A retrospective cohort study of 12,193 women evaluated for infertility between 1965 and 1988 at five clinical sites identified 292 in situ and invasive breast cancers in follow-up through 1999. Standardized incidence ratios (SIRs) compared breast cancer risks with those of the general population. Analyses within the cohort estimated rate ratios (RRs) associated with medications after adjustment for other breast cancer predictors. RESULTS: Infertile patients had a significantly higher breast cancer risk than the general population [SIR = 1.29, 95% confidence interval (CI) 1.1-1.4]. Analyses within the cohort showed adjusted RRs of 1.02 for clomiphene citrate and 1.07 for gonadotrophins, and no substantial relationships to dosage or cycles of use. Slight and non-significant elevations in risk were seen for both drugs after > or = 20 years of follow-up (RRs = 1.39 for clomiphene and 1.54 for gonadotrophins). However, the risk associated with clomiphene for invasive breast cancers was statistically significant (RR = 1.60, 95% CI 1.0-2.5). CONCLUSIONS: Although there was no overall increase in breast cancer risk associated with use of ovulation-stimulating drugs, long-term effects should continue to be monitored.     

An immunogenetic analysis of the T-cell recognition of the major house dust mite allergen Der p 2: identification of high- and low-responder HLA-DQ alleles and localization of T-cell epitopes.

Cellular reactivity to Der p 2, a major allergen of the house dust mite (HDM) Dermatophagoides pteronyssinus, was studied in a group of 41 symptomatic HDM sensitive patients, using fresh peripheral blood mononuclear cells (PBMC) and assays of proliferation. Sixty per cent of the patients responded to Der p2, with reactivities being greater in patients with asthma as one of their clinical manifestations and also in those who had skin-test reactivity to a number of allergens. HLA-DR and -DQ serotyping was undertaken in 39 of the patients and the magnitude of T-cell proliferative responses to Der p 2 were found to be positively associated with DQ7 and negatively associated with DQ2. T-cell determinants within the Der p 2 molecule were identified by assays using a series of overlapping peptides (15- to 19-mers) spanning the entire protein. Fifty-nine per cent of the 41 HDM-sensitive patients responded to one or more of the peptides. All of the peptides were antigenic for at least one of the individuals, indicating the heterogeneity of the human repertoire reactive with Der p 2. There was a substantial variability in the number and location of epitopes recognized by T cells from the different allergic patients, the mean number per patient being 2.3 +/- 1.3 (SD). The most frequently recognized peptide was that spanning residues 111-129, being stimulatory in 66.7%, the other peptides were each recognized by between 8 to 25% of individuals. There was no correlation between the epitope recognized and the presence of particular HLA-DQ antigens.     

Effect of ouabain and metabolic inhibitors on the Na and K movements and nucleotide contents of L cells

1. The general characteristics and Na and K movements of L cells (derived from mouse epithelium) have been measured. Both cells grown in suspension (LS cells) and as a monolayer (L cells) were used.2. The volume of L cells was 1.2 x 10(-9) cm(3) and of LS cells 3.5 x 10(-9) cm(3); of this 82% was water.3. Electron micrographs showed the presence of numerous protrusions (filopodia) from both forms of the cell. These had the effect of increasing the surface area of the cell by 2-4 times over smooth cells of the same volume. On changing from the flattened to the spherical shape during trypsinization, the filopodia altered to maintain a constant V/A ratio.4. These cells contain K, about 170 m-mole/l. intracellular water and Na, 9 m-mole/l. intracellular water (L cells only) at 20 degrees C. The K fluxes are 1.9 p-mole/cm(2) sec for LS cells and 0.8 p-mole/cm(2) sec for L cells and the Na fluxes are 1.8 p-mole/cm(2) sec for L cells (expressed as per total cell surface (including filopodia)). If expressed as p-mole/cell per sec then L and LS cells have the same K flux.5. 10(-4)M ouabain reduces the K influx to half, indicating an insensitivity to the glycosides common to the species. In the prolonged presence of ouabain the cells come into a new steady state with a [K](1), of 140 and a [Na](1) of 20-30 m-mole/l. intracellular water, but a constant [Na + K](1).6. Both DNP (10(-3)M) and IAA (10(-4)M) are required for maximum inhibition of K uptake, as both aerobic and anaerobic metabolic pathways may be used to drive the pump.7. K removal decreases the Na efflux, and Na removal (eventually) decreases the K influx providing evidence for Na/K coupling.8. The cells contain 7.5 m-mole/litre intracellular water of ATP, a level some 15 times that of ADP.9. The Na pump in these cells is very similar to that found in other tissues in that (a) it requires K to work, (b) it is blocked by ouabain and metabolic inhibitors and (c) it transports three molecules of Na for each two molecules of K.     

Novel neuritic clusters with accumulations of amyloid precursor protein and amyloid precursor-like protein 2 immunoreactivity in brain regions damaged by thiamine deficiency.

Experimental thiamine deficiency (TD) is a classical model of a nutritional deficit associated with a generalized impairment of oxidative metabolism and selective cell loss in the brain. In rats, TD-induced cell degeneration is accompanied by an accumulation of amyloid precursor protein (APP)/amyloid precursor-like protein 2 (APLP2) immunoreactivity in abnormal neurites and perikarya along the periphery of, or scattered within, the lesion. Prompted by these data and our previous findings of a genetic variation in the development of TD symptoms, we extended our studies to mice. C57BL/6, ApoE knockout, and APP YAC transgenic mice received thiamine-deficient diet and pyrithiamine injections. Unlike rats, APP/APLP2-immunoreactive neurites in all strains of mice were sparsely scattered within damaged areas and did not delimit the thalamic lesion. In addition, abnormal clusters of intensely immunoreactive neurites occurred only in areas of damage including the thalamus, mammillary body, and inferior colliculus. The clusters appeared as either irregular clumps or round or oval rosettes that strikingly resembled the neuritic component of Alzheimer amyloid plaques. However, immunostaining using various antisera to synthetic amyloid beta-protein (A beta 1-40) and thioflavine S histochemistry failed to show evidence of a component of A beta Neither APP/APLP2-immunoreactive clusters nor amyloid plaques were observed in the brain from patients with Wernicke-Korsakoff syndrome, the clinical manifestation of TD in man. Our results demonstrate species (i.e., genetic) differences in the response to TD-induced damage and support a role for APP and APLP2 in the response to brain injury. This is the first report that chronic oxidative deficits can lead to this novel pathology.