Sentinel node biopsy should be supplemented by axillary sampling in patients with small breast cancers

Axillary clearance provides important prognostic information but is associated with significant morbidity. Sentinel node biopsy can provide staging .141 patients with node negative early breast cancers-tumour size less than 1.5 cm measured clinically or by imaging had guided axillary sampling (sentinel lymph node biopsy in combination with axillary sampling). Four node axillary sampling improved the detection rate of axillary node metastases by 13.6% as compared to blue dye sentinel node biopsy alone. Positive sampled nodes strongly indicated the likelihood of further metastatic being revealed by axillary dissection (67%). Negative sampled nodes in combination with a positive sentinel node biopsy were associated with a much lower rate of further nodal involvement in the axillary clearance (8%).     

Characterization of a novel mutation in the cardiac ryanodine receptor that results in catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease that manifests as syncope or sudden death during high adrenergic tone in the absence of structural heart defects. It is primarily caused by mutations in the cardiac ryanodine receptor (RyR2). The mechanism by which these mutations cause arrhythmia remains controversial, with discrepant findings related to the role of the RyR2 binding protein FKBP12.6. The purpose of this study was to characterize a novel RyR2 mutation identified in a kindred with clinically diagnosed CPVT.Single-strand conformational polymorphism analysis and direct DNA sequencing were used to screen the RyR2 gene for mutations. Site-directed mutagenesis was employed to introduce the mutation into the mouse RyR2 cDNA. The impact of the mutation on the interaction between RyR2 and a 12.6 kDa FK506 binding protein (FKBP12.6) was determined by immunoprecipitation and immunoblotting and its effect on RyR2 function was characterized by single cell Ca²⁺ imaging and [³H]ryanodine binding.A novel CPVT mutation, E189D, was identified. The E189D mutation does not alter the affinity of the channel for FKBP12.6, but it increases the propensity for store-overload-induced Ca²⁺ release (SOICR). Furthermore, the E189D mutation enhances the basal channel activity of RyR2 and its sensitivity to activation by caffeine.The E189D RyR2 mutation is causative for CPVT and functionally increases the propensity for SOICR without altering the affinity for FKBP12.6. These observations strengthen the notion that enhanced SOICR, but not altered FKBP12.6 binding, is a common mechanism by which RyR2 mutations cause arrhythmias.Key words: arrhythmia, calcium, death sudden, genetics, ion channels     

Phenotypic variability and therapeutic implications of Candida species in patients with oral lichen planus

We investigated the prevalence and phenotypic variation of Candida species in oral lichen planus (OLP) and the therapeutic implications of our findings. Eighty patients with clinically and histopathologically confirmed cases of OLP (64 non-erosive, 16 erosive) and a control group of 80 healthy individuals with no predisposing factors for oral candidiasis were examined for evidence of Candida infection. Oral swabs and smears were obtained for cytology and culture. Identification, speciation and antifungal susceptibility tests of Candida isolates were performed using an automated microbial identification system. Fifty percent of erosive OLP cases, 28% of non-erosive cases and none of the controls showed evidence of Candida. Candida albicans was found predominantly in non-erosive OLP, while other Candida species were predominate in erosive OLP. Non-Candida albicans isolates (C. glabrata, C. krusei) were resistant to the commonly used antifungals, clotrimazole and fluconazole. Candida infection is common in cases of OLP. We recommend antifungal sensitivity testing prior to antifungal therapy for the erosive form of OLP.     

Fine mapping of a grain-weight quantitative trait locus in the pericentromeric region of rice chromosome 3

As the basis for fine mapping of a grain-weight QTL, gw3.1, a set of near isogenic lines (NILs), was developed from an Oryza sativa, cv. Jefferson x O. rufipogon (IRGC105491) population based on five generations of backcrossing and seven generations of selfing. Despite the use of an interspecific cross for mapping and the pericentromeric location of the QTL, we observed no suppression of recombination and have been able to narrow down the location of the gene underlying this QTL to a 93.8-kb region. The locus was associated with transgressive variation for grain size and grain weight in this population and features prominently in many other inter- and intraspecific crosses of rice. The phenotype was difficult to evaluate due to the large amount of variance in size and weight among grains on a panicle and between grains on primary and secondary panicles, underscoring the value of using multiple approaches to phenotyping, including extreme sampling and NIL group-mean comparisons. The fact that a QTL for kernel size has also been identified in a homeologous region of maize chromosome 1 suggests that this locus, in which the dominant O. rufipogon allele confers small seed size, may be associated with domestication in cereals.     

Molecular mapping of genes for resistance to rice blast (Pyricularia grisea Sacc.)

Two dominant genes conferring complete resistance to specific isolates of the rice blast fungus, Pyricularia grisea Sacc., were located on the molecular map of rice in this study. Pi-l(t) is a blast resistance gene derived from the cultivar LAC23. Its map location was determined using a pair of nearly isogenic lines (NILs) and a B₆F₃ segregating population from which the isoline was derived. RFLP analysis showed that Pi-l(t) is located near the end of chromosome 11, linked to RZ536 at a distance of 14.0±4.5 centiMorgans (cM). A second gene, derived from the cultivar Apura, was mapped using a rice doubled-haploid (DH) population. This gene was located on chromosome 12, flanked by RG457 and RG869, at a distance of 13.5+-4.3 cM and 17.7+-4.5 cM, respectively. The newly mapped gene on chromosome 12 may be allelic or closely linked toPi-ta. (=Pi-4(t)), a gene derived from Tetep that was previously reported to be linked to RG869 at a distance of 15.4±4.7 cM. The usefulness of markers linked to blast resistance genes will be discussed in the context of breeding for durable blast resistance.     

Chromosomal regions associated with segregation distortion of molecular markers in F2?, backcross, doubled haploid, and recombinant inbred populations in rice ( Oryza sativa L.)

Chromosomal regions associated with marker segregation distortion in rice were compared based on six molecular linkage maps. Mapping populations were derived from one interspecific backcross and five intersubspecific (indica / japonica) crosses, including two F₂ populations, two doubled haploid (DH) populations, and one recombinant inbred (RI) population. Mapping data for each population consisted of 129–629 markers. Segregation distortion was determined based on chi-square analysis (P < 0.01) and was observed at 6.8–31.8% of the mapped marker loci. Marker loci associated with skewed allele frequencies were distributed on all 12 chromosomes. Distortion in eight chromosomal regions bracketed previously identified gametophyte (ga) or sterility genes (S). Distortion in three other chromosomal regions was found only in DH populations, where japonica alleles were over-represented, suggesting that loci in these regions may be associated with preferential regeneration of japonica genotypes during anther culture. Three additional clusters of skewed markers were observed in more than one population in regions where no gametophytic or sterility loci have previously been reported. A total of 17 segregation distortion loci may be postulated based on this study and their locations in the rice genome were estimated. Received: 31 May 1996 / Accepted: 30 September 1996