Anthropogenic control over wintertime oxidation of atmospheric pollutants.

During winter in the mid-latitudes, photochemical oxidation is significantly slower than in summer and the main radical oxidants driving formation of secondary pollutants, such as fine particulate matter and ozone, remain uncertain, owing to a lack of observations in this season. Using airborne observations, we quantify the contribution of various oxidants on a regional basis during winter, enabling improved chemical descriptions of wintertime air pollution transformations. We show that 25-60% of NOx is converted to N2O5 via multiphase reactions between gas-phase nitrogen oxide reservoirs and aerosol particles, with ~93% reacting in the marine boundary layer to form >2.5 ppbv ClNO2. This results in >70% of the oxidizing capacity of polluted air during winter being controlled, not by typical photochemical reactions, but from these multiphase reactions and emissions of volatile organic compounds, such as HCHO, highlighting the control local anthropogenic emissions have on the oxidizing capacity of the polluted wintertime atmosphere.

Developing a framework for admission and discharge: a nurse-led initiative within a mental health setting.

Admission to a mental health inpatient setting is one important aspect of care which requires collaborative working between Community Mental Health Teams (CMHTs) and ward staff. However, links are not always formalized. The failure of effective gatekeeping coupled with inconsistent admission and discharge practices further complicates the situation for all those involved. A number of local changes, for example, adoption of a centralized bed bureau, together with policy changes, initiated a nurse-led practice development project. It was predicted that by creating a framework for more formalized communication between the different disciplines admission and discharge processes would be improved, thus enhancing service users' satisfaction and empowering all staff participating in the process. During the project, 132 service users were notified as potentially requiring admission. Admissions were avoided and diverted for 22 of them. The quality of the communication and information shared between the CMHTs and ward staff was significantly improved. Accessing inpatient beds, at times still remained problematic, as beds could only remain ring-fenced on 65% of occasions. This initiative, conducted within a 'real world setting', showed that it is possible to improve admission and discharge practices by creating a framework for a formalized communication process between disciplines.

Multiple carbohydrate-cleaving specificities in human acidic and neutral glycosidases.

The common identity of human acidic beta-D-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) and beta-D-xylosidase (1,4-beta-D-xylan xylohydrolase, EC 3.2.1.37) as one enzyme and that of acidic beta-D-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23), beta-D-fucosidase (no allotted EC number) and alpha-L-arabinosidase (alpha-L-arabinofuranoside arabinohydrolase, EC 3.2.1.55) as another enzyme is indicated by similar binding patterns of glycosidase activities of each enzyme to various lectins. by similar ratios between their intra- and extracellular levels in normal and I-cell fibroblasts and by their deficiencies in liver tissues from patients with Gaucher disease and GM1 gangliosidosis, respectively. A third enzyme, neutral beta-D-galactosidase, purified to homogeneity from human liver has been shown to possess all these five glycosidase activities at neutral pH. These neutral enzymic activities were not bound by any of the lectins examined and found to be reduced in liver and spleen of a patient with neutral beta-D-galactosidase deficiency. An additional form of beta-D-xylosidase with optimal activity at pH 7.4 was bound by the fucose-binding lectin from Ulex eurpaeus while no binding was observed for the acidic (pH 4.8) and neutral (pH 7.0) beta-D-xylosidase activities of the multiple glycosidase enzymes.

Expression of SRY transcripts in preimplantation human embryos.

We have examined the expression of SRY mRNA in individual in vitro fertilized preimplantation human embryos; because of ethical constraints, these studies were confined to embryos with one and three pronuclei. Using a sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay, we observed SRY mRNA at the one-cell through the blastula stages but not in spermatozoa. These results indicate that the de novo transcription of this sex-specific gene occurs at a developmental time considerably earlier than that of gonadal differentiation. Our results also indicate that in vitro fertilized embryos with one pronucleus are likely to be diploid.

Adverse pregnancy outcome after a false-positive screen for Down syndrome using multiple markers.

OBJECTIVE: To assess the relative risk of an adverse pregnancy outcome in women whose multiple-marker screening (maternal serum alpha-fetoprotein [MSAFP], unconjugated estriol [E3], and hCG levels, and age) indicating an increased risk for Down syndrome (more than 1:250) was not confirmed by amniocentesis. METHODS: Fifty-eight women with false-positive screens for Down syndrome were matched with a control group of 116 women whose screens indicated a risk for Down syndrome of less than 1:250. The risk for adverse pregnancy outcome was compared for the two groups, and the roles of MSAFP, unconjugated E3, and hCG as predictors of adverse pregnancy outcome were determined. RESULTS: Women with false-positive screens for Down syndrome were significantly different from their matched controls in the incidence of preterm delivery (20.6 versus 8.6%, respectively), preeclampsia (6.9 versus 0%), small for gestational age newborns (5.2 versus 0%), and fetal demise after 20 weeks' gestation (5.2 versus 0%). An adverse outcome occurred in 19 of 58 pregnancies (32.8%) in the study group and in 14 of 116 matched control pregnancies (12%) (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.6-7.8; P < .01). Unconjugated E3 of 0.75 multiples of the mean (MoM) or less was significantly associated with adverse pregnancy outcome after controlling for the effects of MSAFP and hCG (OR 2.5, 95% CI 1.13-5.55; P < .02). CONCLUSION: One in three women with a false-positive screen for Down syndrome may experience an adverse pregnancy outcome. In this study, unconjugated E3 of 0.75 MoM or less appeared to be a better predictor of adverse pregnancy outcome than were MSAFP and hCG levels.

At the crossroads: the intersection of the Internet and clinical oncology.

The Internet is rapidly becoming a third party in the doctor-patient relationship. The World Wide Web, electronic mail (e-mail), and discussion groups have dramatically increased the quantity of medical and health information available to patients, who, in turn, vary greatly in their understanding of that newly discovered information. This article reviews the advantages and disadvantages of the Internet for both oncology patients and physicians. This forms the background for a discussion of three steps that clinical oncologists and other health care professionals can take to direct and control the potential of the Internet so as to optimize patient care. These steps include: (1) finding out what type of cancer information is being disseminated on the Web; (2) using Internet-derived material that patients bring to the clinic as a stepping-stone for patient education; and (3) becoming an active participant on the Web. Each of these strategies requires health professionals to be proactive. The appropriate and effective use of the Internet, as well as its boundaries, are rapidly expanding in medicine and are likely to co-evolve with changes in patient-health care provider relationships.

Discordance among blastomeres renders preimplantation genetic diagnosis for aneuploidy ineffective.

PURPOSE: To investigate the contribution of discordance among blastomeres from the same embryo in the interpretation of blastomeres biopsied from day 3 embryos. METHODS: 228 IVF embryos had two blastomeres removed and fluorescent in situ hybridization (FISH) was used to detect aneuploidy of chromosomes 13, 15, 16, 18, 21, 22, X and Y. Of the 228 embryos, 102 had complete FISH results for both blastomeres. RESULTS: When the 2 blastomeres of 102 embryos with successful FISH results were compared, 26 (25.5%) were concordant for all 8 chromosomes and 76 (74.5%) were discordant for one or more chromosomes. Among the 102 embryos, 12 (12%) were disomy in both blastomeres and 37 (36%) were disomic in all 8 chromosomes in one of the two blastomeres. CONCLUSION: Discordance among blastomeres from the same embryo appears to present a significant problem in interpreting results of embryos biopsied on day 3 and analyzed by FISH especially when most PGD's are done on single blastomeres.

The expression of genes in human preimplantation embryos.

The study of gene expression in human preimplantation embryos is establishing itself as a necessary dimension of developmental biology and medical genetics. Transcripts identified in human preimplantation embryos include housekeeping genes, transcription and growth factor genes, sex-determining genes, tissue-specific genes and novel genes, as well as genes of unknown function. Strategies are being developed which will eventually permit the most sophisticated gene expression studies on single human embryos of co-ordinated transcription and translational regulation. There is both a need for international co-operation for the systematic construction of expression maps and a need to establish databases of expression patterns during different stages of human development. Understanding how genes are regulated in humans is essential for understanding both normal development and disease. Until recently, studies of gene expression and regulation during embryogenesis were almost exclusively limited to prokaryotes and to eukaryotes other than man. The introduction of artificial reproductive technologies in conjunction with the development of recombinant molecular technologies applicable to single cells has made possible the study of human development at its earliest stages (Pergament and Bonnicksen, 1994). Although there are still enormous technical challenges, robust strategies have been, and continue to be, developed for connecting DNA sequence to such endophenotypes as timing and level of genes expression at the single cell level. Questions currently being asked in human developmental genetic studies concern the pronucleus, the zygote and the preimplantation embryo: what genes are expressed? When are they expressed? What functions do they perform and how, in sequence or in combination? And, what elements control and regulate their expression? This review provides an overview of current knowledge about the expression of different embryonic genes during early human development and discusses future prospects, which includes a need for international co-operation similar to the Human Genome Project.

The role of the preimplantation geneticist in human cloning.

If human cloning is to become a reality, the preimplantation geneticist must be responsible for determining the indications for undertaking cloning and for establishing the risks and benefits of human cloning. The unresolved issue is whether a compelling argument can be made for cloning a human for therapeutic reasons while outweighing legal, moral and ethical objections. At present, 'whole person' cloning does not seem justified under any circumstance, whereas cloning for the replacement of diseased cells, tissues or organ systems, i.e. 'spare parts', seems to be a likely, acceptable application of cloning strategies for humans.

The clinical application of interphase FISH in prenatal diagnosis.

Fluorescence in situ hybridization (FISH) for five chromosomes (13, 18, 21, X and Y) detected 87 of 107 (81%) of the chromosome aberrations identified by conventional chromosome analysis applied to fetal interphase cells obtained by chorionic villus sampling or amniocentesis. The choice of FISH was solely determined by prospective parents after formal genetic counselling concerning the advantages and disadvantages of FISH analysis. Excluding known familial chromosome aberrations, if FISH analysis revealed normal signals, there was an overall residual risk of 1 in 149 for an undetectable chromosome aberration. This risk varied according to the indication for prenatal diagnosis: 1 in 177 for women of advanced maternal age; 1 in 60 for women at increased risk for Down syndrome based on maternal serum screening; and, 1 in 43 for women whose ultrasound examination revealed fetal anomalies. There were 20 cases of discordance between the FISH results and standard karyotype analysis: four were the outcome of a failure to apply the appropriate FISH probe; 16 were not detectable by the available FISH probes. Of these 16, nine were chromosome abnormalities with clinical significance and seven were familial. If FISH is to become a standard part of prenatal genetic diagnosis, genetic counselling that is sensitive to patient health needs must be based on accurate information about the biological and obstetrical implications of the results of FISH analysis.

A case-based approach to the development of practice-based competencies for accreditation of and training in graduate programs in genetic counseling.

The American Board of Genetic Counseling (ABGC) sponsored a consensus development conference with participation from directors of graduate programs in genetic counseling, board members, and expert consultants. Using a collective, narrative, and case-based approach, 27 competencies were identified as embedded in the practice of genetic counseling. These competencies were organized into four domains of skills: Communication; Critical Thinking; Interpersonal, Counseling, and Psychosocial Assessment; and Professional Ethics and Values. The adoption of a competency framework for accreditation has a variety of implications for curriculum design and implementation. We report here the process by which a set of practice-based genetic counseling competencies have been derived; and in an accompanying article, the competencies themselves are provided. We also discuss the application of the competencies to graduate program accreditation as well as some of the implications competency-based standards may have for education and the genetic counseling profession. These guidelines may also serve as a basis for the continuing education of practicing genetic counselors and a performance evaluation tool in the workplace.

Practice-based competencies for accreditation of and training in graduate programs in genetic counseling.

In January 1996, the American Board of Genetic Counseling (ABGC) adopted 27 practice-based competencies as a standard for assessing the training of graduate students in genetic counseling. These competencies were identified and refined through a collective, narrative process that took place from January through November 1994, and included directors of graduate programs in genetic counseling, ABGC board members and expert consultants. These competencies now form the basis of the document "Requirements for Graduate Programs in Genetic Counseling Seeking Accreditation by the American Board of Genetic Counseling" (American Board of Genetic Counseling, 1996). The competencies are organized into four domains and are presented and discussed in this article.

Binding of human liver hydrolases by immobilized lectins.

The binding of 22 human liver hydrolase activities by immobilized lectins of six different carbohydrate specificities, namely alpha-D-mannose (glucose), D-N-acetylglucosamine, D-N-acetylgalactosamine, L-fucose, alpha-D-galactose and beta-D-galactose, were examined. Differences in binding among these enzymes and within specific enzymes were observed. For example, the neutral forms of alpha-mannosidase and beta-xylosidase were bound by the Ulex europaeus lectin I (specific for L-fucose), whereas the acidic forms were not. Bandierea simplicifolia lectin (specific for alpha-galactose) bound 65% of beta-glucuronidase activity; recycling experiments demonstrated complete binding of the enzyme that had been eluted with the competitor D-galactose and no binding of the fraction that was not initially bound. These results suggested the presence of two forms of this enzyme. Similar data were obtained for acidic beta-galactosidase activity. These experiments may provide the basis for the expanded use of immobilized lectins for purification and characterization of hydrolases and other glycoproteins.

Breast-feeding and postpartum relapse in women with rheumatoid and inflammatory arthritis.

OBJECTIVE: To test the hypothesis that breast-feeding increases the risk of postpartum flare in inflammatory polyarthritis. METHODS: We compared disease activity during pregnancy and at 6 months postpartum among 49 non-breast-feeders, 38 first-time breast-feeders, and 50 repeat breast-feeders. RESULTS: After we adjusted for possible confounders, including treatment, first-time breast-feeders had increased disease activity 6 months postpartum, based on self-reported symptoms, joint counts, and C-reactive protein levels. CONCLUSION: Postpartum flare may be induced by breast-feeding.

Expression of transcription regulating genes in human preimplantation embryos.

Utilizing a sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay system, the time course of mRNA expression of two transcription regulators, OCT4 and OCT6, was assessed in individual preimplantation human embryos. Examination of ova with three pronuclei and 1-cell through blastocyst stage embryos revealed that OCT4 mRNA was continuously expressed between the time of fertilization and 10+ cell stages, whereas OCT6 mRNA expression was not observed until the 10+ cell stage. The difference in the time of expression of OCT4 mRNA and OCT6 mRNA indicates that the two genes play differential roles in human embryogenesis. Nucleotide sequence homology for OCT4 and OCT6 among mammalian organisms supports the concept that genetic elements determining developmental events during embryogenesis are conserved in evolution.

Immunologic aspects of enzyme replacement therapy. An evaluation of the immune response to unentrapped, erythrocyte- and liposome-entrapped enzyme in C3H/HeJ Gush mice.

The ability of autologous erythrocytes and liposomes to provide nonimmunogenic vesicles which protect entrapped enzyme from immunologic surveillance and initiation of an immune response was assessed in C3H/HeJ Gush mice following repeated administration of these vesicles with and without entrapped enzyme. Erythrocyte-entrapped bovine beta-glucuronidase elicited no antibody response detectable by double diffusion, passive hemagglutination, complement-dependent lysis, or time-course experiments. Moreover, erythrocyte entrapment protected the enzyme from circulating antibody in mice previously sensitized with unentrapped enzyme. In contrast, repeated IV injection of negatively-charged liposomes loaded with enzyme induced both humoral and cellular responses. Low levels of antibody to the bovine enzyme were detectable by the double antibody technique; no antibodies to the liposome were detectable by complement lysis. In time-course experiments, significant decreases in tissue recoveries of liposome-entrapped beta-glucuronidase were observed in mice sensitized with enzyme-loaded liposomes compared to the recoveries in unsensitized mice, due in part to the rapid degradation of antigen-antibody complexes. A similarly decreased tissue recovery of liposome-entrapped enzyme was apparent in mice with circulating anti-beta-glucuronidase antibody, indicating the inability of liposomes to protect entrapped protein from immunologic surveillance. The cellular response to the liposome vesicle was characterized by the enhanced phagocytic activity of reticuloendothelial cells in the liver and spleen, and the activation of peritoneal macrophages. These results identify erythrocytes as nonimmunogenic carriers capable of protecting entrapped protein from immunologic surveillance and therefore suitable for enzyme replacement endeavors. However, the demonstration that both buffer- and enzyme-loaded liposomes induce an immune response mandates further investigation of these carriers prior to clinical trials of liposome-entrapped therapeutic agents.