Serial order short-term memory capacities and specific language impairment: No evidence for a causal association

This study re-explored the nature of verbal short-term memory (STM) deficits in children with specific language impairment (SLI), by distinguishing item and serial order STM processes. Recent studies have shown serial order STM capacity to be a critical determinant of language development, relative to item STM. In Experiment 1, 12 children with SLI, 12 age-matched children and 12 language-matched children were administered serial order recognition and reconstruction tasks. Experiment 2 assessed implicit serial learning abilities via a Hebb learning task. The SLI group showed impaired performance for the serial order reconstruction and recognition tasks, relative to language-matched and/or age-matched control groups. However, normal serial position effects were observed in all SLI children in the serial order reconstruction task, suggesting normal coding of serial position information. Similarly, performance on the Hebb serial learning task was at chronological age appropriate levels. Experiment 3 showed that the group differences observed for the serial order STM tasks in Experiment 1 disappeared when the SLI group was compared to a mental age-matched control group. Experiment 4 showed similar performance levels in the SLI group and the mental age-matched control group for a nonword recognition task assessing item STM capacities. This study shows that children with SLI have no specific impairments for serial order and item STM components but that poorer general cognitive efficiency is related to functional limitations in verbal STM tasks. The data are in line with limited information processing accounts of SLI.     

TP53 mutations in prostatic cancer. Analysis of pre- and post-treatment archival formalin-fixed tumour tissue

The TP53 gene mutation pattern in prostatic cancer was examined in relation to progression and survival, using archival formalin-fixed pre-and post-treatment tumour specimens from 84 prostatic cancer patients. Thirty-four had hormone-sensitive tumours and 50 were hormone-resistant. Six of the 34 (18 per cent) therapy-responding tumours and 19 of the 50 (38 per cent) hormone-resistant tumours showed p53 protein accumulation in the post-treatment specimen. Both pre- and post-treatment specimens from these 25 patients were analysed for mutation of the conserved regions of the TP53 gene (exons 5–8), using constant denaturant gel electrophoresis (CDGE) followed by DNA sequencing. In the post-treatment samples, mutations were detected in three of the six patients with hormone-responsive tumours and in 11 of the 19 patients with hormone-resistant tumours. The three (100 per cent) patients with therapy-responsive tumours with mutations and nine of the 11 (82 per cent) patients with therapy-resistant tumours with mutations died of the disease. Thirteen of the 14 mutations in the post-treatment specimens were transitions, 11 occurring at CpG dinucleotides in which codon 273 was involved in ten. A significantly higher proportion of tumours with mutations were poorly differentiated compared with tumours without mutation (P<0·04). Our findings indicate that TP53 mutation is a late event in tumour development of the prostate gland and that codon 273 might be a ‘hotspot’ for mutation in the progression of the disease.     

No germline TP53 mutations detected in familial and bilateral testicular cancer

Mutations in the TP53 gene are considered to be among the most common genetic alterations in human cancers. Both somatic and germline mutations have been found. Using potymerase chain reaction (PCR), constant denaturant gel electrophoresis (CDGE), and denaturing gradient gel electrophoresis (DGGE), we have examined 32 patients with bilateral and familial germ cell tumors (GCT) and two patients with sporadic GCT for germline mutations within the conserved regions of the gene. In addition, 15 tumors were screened for somatic mutations and analyzed for loss of heterozygocity (LOH) at the TP53 locus. Twelve tumors were analyzed for expression of TP53 via immunohistochemistry. Neither germline nor somatic TP53 mutations were deteeted. LOH was observed in one of five informative cases. No tumors showed increased expression of TP53 protein. These results indicate that alterations in the TP53 gene are not important for the predisposition to and development of GCT. © 1993 Wiley-Liss, Inc.     

Marfan syndrome: exclusion of genetic linkage to the COL1A2 gene

Marfan Syndrome is a genetic disorder of the connective tissue. Individuals from one large family with this disorder were genotyped for COL1A2 gene associated RFLPs. Our results demonstrated that the COL1A2 gene, encoding the proa2(I) collagen chain, segregated independently of the phenotype and it is therefore excluded as the mutant locus in this family.     

Dynamic responses of oxygen uptake at the onset and end of moderate and heavy exercise in trained subjects.

Inconsistencies about dynamic asymmetry between the on- and off-transient responses in VO2 are found in the literature. Therefore the purpose of this study was to examine VO2 on- and off-transients during moderate- and heavy-intensity cycling exercise in trained subjects. Ten men underwent an initial incremental test for the estimation of ventilatory threshold (VT) and, on different days, two bouts of square-wave exercise at moderate (VT) intensities. VO2 kinetics in exercise and recovery were better described by a single exponential model (VT). For moderate exercise, we found a symmetry of VO2 kinetics between the on- and off-transients (i.e., fundamental component), consistent with a system manifesting linear control dynamics. For heavy exercise, a slow component superimposed on the fundamental phase was expressed in both the exercise and recovery, with similar parameter estimates. But the on-transient values of the time constant were appreciably faster than the associated off-transient, and independent of the work rate imposed (VT). Our results do not support a dynamically linear system model of VO2 during cycling exercise in the heavy-intensity domain.     

What Can Be Learned from a Lattice Analysis of a Laterality Questionnaire?

In order to develop a genetic study of human laterality, we conducted an exploratory study concerning one aspect of this phenotype: lattice analysis was used to determine whether the structure of manual preference was the same for right- and left-handers. The study highlights the links between two sets — participants and actions — describing binary data, by ordering them dually along a Galois lattice: participants were ordered according to subsets of actions for which they used only their writing hand, while actions were ordered according to sub-groups using their writing hand to perform them. The twelve item questionnaire of Annett was analysed in two samples of 94 adult right-hand and 31 left-hand writers. The items did not have the same categorical impact for the two groups of left- and right-hand writers. The behaviour of right-handers appeared globally more stereotyped. On the contrary, left-handed profiles were nearly all distinct. To explore these conclusions more thoroughly in the general population would certainly require greater samples. Nevertheless in both cases the observed structures were highly dimensional, a result that would grow stronger as the group sizes increase. Hence whereas some questionnaires purport to evaluate laterality along an unidimensional continuum, the present analysis questions such a strong assumption providing evidence to the contrary.     

Effect of intensive swimming training on lung volumes, airway resistances and on the maximal expiratory flow-volume relationship in prepubertal girls

The aim of the present study was to analyse the effect of 1 year of intensive swimming training on lung volumes, airway resistance and on the flow-volume relationship in prepubertal girls. Five girls [9.3 (0.5) years old] performing vigorous swimming training for 12?h a week were compared with a control group of 11 girls [9.3 (0.5) years old] who participated in various sport activities for 2 h per week. Static lung volumes, maximal expiratory flows (MEF) at 75, 50 and 25% of vital capacity, 1-s forced expiratory volume (FEV_1.0) and airway resistance (R _aw) were measured by means of conventional body plethysmograph techniques. Prior to the training period there were no significant differences between the two groups for any of the parameters studied. Moreover, for both groups, all parameters were within the normal range for children of the corresponding age. After 1 year of training, vital capacity (VC), total lung capacity (TLC) and functional residual capacity (FRC) were larger (P<0.05) in the girl swimmers than in the control group, while physical development in terms of height and weight was similar. FEV_1.0 (P<0.01), MEF₂₅, MEF₅₀ (P<0.05) and MEF₇₅ as well as the ratio MEF₅₀ / TLC (P<0.05) had increased in the girl swimmers but were unchanged in the control group. R _aw tended to be lower in the girl swimmers and higher in the control group. The results indicate that intensive swimming training prepuberty enhances static and dynamic lung volumes and improves the conductive properties of both the large and the small airways. As to the causative mechanism, it can be speculated that at prepuberty intensive swimming training promotes isotropic lung growth by harmonizing the development of the airways and of alveolar lung spaces.     

PIK3CA mutations in advanced ovarian carcinomas

PIK3CA belongs to the phosphatidylinositol 3-kinases (PI3Ks) family, which play an important role in proliferation, adherence, transformation and cell survival through the PI3K/AKT signaling pathway. Somatic activating mutations of this gene have recently been detected in several types of cancers. In the present study, 109 advanced ovarian carcinomas were analyzed for PIK3CA mutations in exon 9 and exon 20 by direct sequencing. Activating missense mutations were observed in 4 of the 109 tumors in addition to one variant leading no change of the PIK3CA protein. Two of the cases with mutations were mucinous and clear cell tumors, suggesting that PIK3CA mutations are more common in these rare histological types.     

Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas.

Fifty-nine primary breast carcinomas and 11 metastases were examined to identify genetic alterations in the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q. Loss of heterozygosity (LOH) was frequently observed on chromosome arms 17p (p144D6 lost in 75%, pYNZ22.1 in 55%, and TP53 in 48% of the primary tumours), 13q (RBI lost in 40% of the primary tumours), and 17q (pRMU3 lost in 35%, pTHH59 in 29%, and NM23HI in 26% of the primary tumours). Loss of all the markers except p144D6 was observed even more frequently in the metastases. Pairwise comparisons for concordance of allele losses on 17p indicated that there might be two genes on 17p implicated in breast cancer development; the TP53 gene and a gene located close to the p144D6 and pYNZ22.1 markers. LOH of the RBI gene was associated with LOH of pYNZ22.1 and p144D6, but not with LOH of TP53. LOH of RBI and TP53 was associated with occurrence of ductal carcinomas, RBI and p144D6 losses with tumour size, and p144D6 losses with positive node status as well. LOH of TP53 and the three 17q markers NM23HI, pTHH59, and pRMU3 was most frequently observed in tumours from postmenopausal women. p144D6 losses occurred most frequently in progesterone receptor-negative tumours, whereas pTHH59 losses occurred most frequently in oestrogen receptor-negative tumours. LOH of the investigated loci was not associated with ERBB2 protooncogene amplification, with positive family history of breast cancer, or with survival.     

TP53 gene mutations predict the response to neoadjuvant treatment with 5-fluorouracil and mitomycin in locally advanced breast cancer.

PURPOSE: Recent studies have found an association between certain TP53 mutations and resistance to anthracycline-based primary medical therapy in breast cancer. The purpose of this study was to investigate whether TP53 mutational status also might influence the response to a non-anthracycline-containing regimen in primary breast cancer. EXPERIMENTAL DESIGN: Thirty-five patients with locally advanced breast cancer were investigated for TP53 mutations before receiving combination chemotherapy with 5-fluorouracil (1000 mg/m(2) on days 1 and 2) and mitomycin (6 mg/m(2) on day 2), administered every 3 weeks for 2-10 cycles in the neoadjuvant setting. RESULTS: Mutations in the TP53 gene, in particular those affecting loop domains L2 or L3 of the p53 protein, were associated with lack of response to chemotherapy (i.e., increase in the diameter product of tumor lesion by >/=25%; P = 0.177 for all mutations and P = 0.006 for those affecting L2/L3 domains, respectively). No statistically significant correlation between TP53 LOH and response to therapy was seen. CONCLUSION: This study revealed a significant association between lack of response to 5-fluorouracil and mitomycin and mutations affecting the L2/L3 domains of the p53 protein. Together with our previous finding that such mutations predict resistance to weekly doxorubicin, our data suggest that mutations affecting this particular domain of the p53 protein may cause resistance to several different cytotoxic compounds applied in breast cancer treatment.