Kinds and locations of mutations arising spontaneously in the coding region of theHPRT gene of finite-life-span diploid human fibroblasts

Spontaneous thioguanine-resistant mutants were derived from populations of finite-life-span, diploid human fibroblasts by means of a fluctuation analysis. cDNA was prepared from mutantHPRT mRNA and amplified by the polymerase chain reaction, and the sequence of the product was analyzed. Exon deletions, which very likely arose from mutations in the intron splice site consensus sequences, were found in 10 of the 37 mutants examined (27% of the total). Among the 28 mutations in the coding sequence, base pair substitutions predominated (89%). With the exception of one base pair involved in a tandem mutation, all base pair substitutions resulted in alterations in the predicted amino acid sequence of the protein. In addition there were three frameshift mutations, consisting of the deletion of one or two base pairs. Although mutations occurred throughout the coding sequence, 50% (14/28) were found in the 5 portion of exon 3.     

HSD17B1 gene polymorphisms and risk of endometrial and breast cancer.

Estrogen exposure influences breast and endometrial cancer risk. The HSD17B1 gene produces an enzyme that catalyzes the conversion of estrone to estradiol. We hypothesized that genetic variations in HSD17B1 gene may alter endogenous estrogen levels and, thus, influence endometrial and breast cancer risk. We validated and genotyped polymorphisms in the HSD17B1 gene and assessed whether these single nucleotide polymorphisms (SNPs), or the imputed haplotypes, were associated with endometrial and breast cancer risk. We also assessed whether a priori risk factors modified the associations between HSD17B1 genotype and cancer risk, and whether HSD17B1 genotypes were associated with plasma estrogen levels among postmenopausal women not using hormone replacement therapy. Ten SNPs of HSD17B1 gene were validated in 30 women from the Nurses' Health Study. Using the expectation maximization algorithm, three common (>5% frequency) haplotypes accounted for 97% of the chromosomes at this locus, and seven SNPs were in complete linkage disequilibrium. We identified and genotyped two haplotype-tagging SNPs (+1004C/T and +1322C/A), and genotyped an additional SNP [+1954A/G (Ser312Gly)] in nested case-control studies of endometrial cancer (cases = 222, controls = 666) and breast cancer (cases = 1007, controls = 1441) in the prospective Nurses' Health Study. Although no overall association by SNP or haplotype analysis was observed with endometrial or breast cancer risk, the +1954A/A genotype was associated with higher estradiol levels in lean women (P = 0.01) and interaction between the +1954 genotype with body mass index in postmenopausal breast cancer (P = 0.05) was suggested. These findings suggest that the HSD17B1 may be associated with circulating estradiol levels and interact with body mass index in postmenopausal breast cancer.     

Pseudomixoma peritoneal tipo adenomucinosis peritoneal diseminada con imágenes radiológicas atípicas

Pseudomyxoma peritonei is an unusual condition that has caused much confusion regarding its aetiology, clinical manifestations, treatment and prognosis. It is characterised by mucinous ascites and diffuse mucinous invasions of the peritoneum. Three histological subtypes have been defined: a) disseminated peritoneal adenomucinosis (peritoneal lesions composed of abundant extra-cellular mucin containing scant simple-to-focally-proliferating mucinous epithelium with little cytological atypia or mitotic activity); b) peritoneal mucinous carcinomatosis (peritoneal lesions composed of more abundant mucinous epithelium with the architectural and cytological features of carcinoma); and c) an intermediate group. The different histological subtypes have different prognoses. We report a case of disseminated peritoneal adenomatosis, and discuss its clinical management.     

Ethical issues in neonatal intensive care and physicians' practices: A European perspective

An international project (EURONIC) was carried out to explore the end-of-life decision-making process in a large, representative sample of neonatal intensive care units (NICUs) in eight western European countries: France, Germany, Great Britain, Italy, Luxembourg, the Netherlands, Spain and Sweden. Structured questionnaires were used to record data on NICU organization and policies, and to survey staff views and practices regarding ethical decision-making. One hundred and twenty-two NICUs were recruited by census or random sampling (response rate 86%); 1235 physicians and 3115 nurses completed the staff questionnaire (response rates 89 and 85%, respectively). This paper focuses on the physicians' answers. In all countries but Italy, most physicians reported having been involved at least once in setting limits to intensive care because of a baby's incurable condition and/or poor neurological prognosis. Adopted strategies varied between countries. Practices such as the continuation of current treatment without intensifying it and the withholding of emergency manoeuvres appeared widespread. In contrast, the frequency of doctors reporting withdrawal of mechanical ventilation was highest in the Netherlands (93%), Sweden (91%) and the Great Britain (88%), intermediate in France and Germany, and lowest in Spain and Italy (34 and 21%, respectively).
Conclusion: Ethically problematic clinical cases are approached differently in the various countries. The findings of this study may provide an opportunity for physicians to review their practices critically, in light of how other colleagues proceed, and foster an open discussion about these difficult issues.     

Visual Attention and Key Word Sign in Children with Autism Spectrum Disorder

The aim of this study was to examine the relationship between children’s visual attention to, and acquisition of, Key Word Sign (KWS). Our hypothesis was that children’s visual attention to the clinician’s modelling would be associated with their acquisition and production of KWS. A multiple baseline single case experimental design with additional exploratory analyses was used to examine the effect of visual attention on sign acquisition among three preschool children with ASD. This paper extends from the previous intervention study (see Tan et al. 2014) by examining visual attention as a potential factor underpinning individual differences in sign acquisition documented in the initial study. All three children visually attended to the clinician’s modelling of KWS, and acquired signs to varying degrees following the introduction of KWS intervention. A weak, non-significant correlation was found between the children’s amount of visual attention and their production of signs. The results provide preliminary evidence for a lack of association between children’s amount of ‘looking’ and ‘doing’ during KWS intervention. Replication and examination of other factors impacting on KWS intervention outcomes is required.     

Photochemistry of aqueous pyruvic acid

The study of organic chemistry in atmospheric aerosols and cloud formation is of interest in predictions of air quality and climate change. It is now known that aqueous phase chemistry is important in the formation of secondary organic aerosols. Here, the photoreactivity of pyruvic acid (PA; CH₃COCOOH) is investigated in aqueous environments characteristic of atmospheric aerosols. PA is currently used as a proxy for α-dicarbonyls in atmospheric models and is abundant in both the gas phase and the aqueous phase (atmospheric aerosols, fog, and clouds) in the atmosphere. The photoreactivity of PA in these phases, however, is very different, thus prompting the need for a mechanistic understanding of its reactivity in different environments. Although the decarboxylation of aqueous phase PA through UV excitation has been studied for many years, its mechanism and products remain controversial. In this work, photolysis of aqueous PA is shown to produce acetoin (CH₃CHOHCOCH₃), lactic acid (CH₃CHOHCOOH), acetic acid (CH₃COOH), and oligomers, illustrating the progression from a three-carbon molecule to four-carbon and even six-carbon molecules through direct photolysis. These products are detected using vibrational and electronic spectroscopy, NMR, and MS, and a reaction mechanism is presented accounting for all products detected. The relevance of sunlight-initiated PA chemistry in aqueous environments is then discussed in the context of processes occurring on atmospheric aerosols.