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Biomedical subjects

J Hansen

Publications and source records attributed to J Hansen.

At least 91 records · Page 5Linked to original sources
PubMed1999

Scanning the available Dictyostelium discoideum proteome for O-linked GlcNAc glycosylation sites using neural networks.

Dictyostelium discoideum has been suggested as a eukaryotic model organism for glycobiology studies. Presently, the characteristics of acceptor sites for the N-acetylglucosaminyl-transferases in Dictyostelium discoideum, which link GlcNAc in an alpha linkage to hydroxyl residues, are largely unknown. This motivates the development of a species specific method for prediction of O-linked GlcNAc glycosylation sites in secreted and membrane proteins of D. discoideum. The method presented here employs a jury of artificial neural networks. These networks were trained to recognize the sequence context and protein surface accessibility in 39 experimentally determined O-alpha-GlcNAc sites found in D. discoideum glycoproteins expressed in vivo. Cross-validation of the data revealed a correlation in which 97% of the glycosylated and nonglycosylated sites were correctly identified. Based on the currently limited data set, an abundant periodicity of two (positions-3, -1, +1, +3, etc.) in Proline residues alternating with hydroxyl amino acids was observed upstream and downstream of the acceptor site. This was a consequence of the spacing of the glycosylated residues themselves which were peculiarly found to be situated only at even positions with respect to each other, indicating that these may be located within beta-strands. The method has been used for a rapid and ranked scan of the fraction of the Dictyostelium proteome available in public databases, remarkably 25-30% of which were predicted glycosylated. The scan revealed acceptor sites in several proteins known experimentally to be O-glycosylated at unmapped sites. The available proteome was classified into functional and cellular compartments to study any preferential patterns of glycosylation. A sequence based prediction server for GlcNAc O-glycosylations in D. discoideum proteins has been made available through the WWW at http://www.cbs.dtu.dk/services/DictyOGlyc/ and via E-mail to DictyOGlyc@cbs.dtu.dk.

Algorithms↗
PubMed1999

Safety and immunogenicity of heptavalent pneumococcal CRM197 conjugate vaccine in infants and toddlers.

OBJECTIVES: The objectives of this study were (1) to determine the safety and immunogenicity of heptavalent pneumococcal CRM197 conjugate (PNCRM7) vaccine in infants and (2) to determine the effect of concurrent hepatitis B immunization during the primary series and the effect of concurrent diphtheria and tetanus toxoid and acellular pertussis [DTaP (ACEL-IMUNE)] and conjugate CRM197 Haemophilus influenzae type b [HbOC (HibTITER) immunization at time of the booster dose on the safety and immunogenicity of PNCRM7and these other concurrently administered vaccines. METHODS: This was a randomized double-blinded study in 302 healthy infants in the Northern California Kaiser Permanente (NCKP) Health Plan. Infants received either PNCRM7 vaccine or meningococcal group C conjugate vaccine as a control at 2, 4 and 6 months of age and a booster at 12 to 15 months of age. Study design permitted the evaluation of immunology and safety of concurrent administration of routine vaccines. Antibody titers were determined on blood samples drawn before and 1 month after the primary series and the booster dose. RESULTS: After the third dose of PNCRM7 geometric mean concentrations (GMCs) ranged from 1.01 for serotype 9V to 3.72 microg/ml for serotype 14. More than 90% of all subjects had a post-third dose titer of > or =0.15 microg/ml for all serotypes, and the percentage of infants with a post-third dose titer of > or =1.0 microg/ml ranged from 51% for type 9V to 89% for type 14. After the PNCRM7 booster dose, the GMCs of all seven serotypes increased significantly over both post-Dose 3 and pre-Dose 4 antibody levels. In the primary series there were no significant differences in GMCs of pneumococcal antibodies between the subjects given PN-CRM7 alone or concurrently with hepatitis B vaccine. At the toddler dose concurrent administration of PNCRM7 and DTaP and HbOC resulted in a near conventional threshold for statistical significance of a post-Dose 4 GMC for serotype 23F [alone 6.75 mirog/ml vs. concurrent 4.11 microg/ml (P = 0.057)] as well as significantly lower antibody GMCs for H. influenza polyribosylribitol phosphate, diphtheria toxoid, pertussis toxin and filamentous hemagglutinin. For all antigens there were no differences between study groups in defined antibody titers that are considered protective. CONCLUSION: We conclude that PNCRM7 vaccine was safe and immunogenic. When this vaccine was administered concurrently at the booster dose with DTaP and HbOC vaccines, lower antibody titers were noted for some of the antigens when compared with the antibody response when PNCRM7 was given separately. Because the GMCs of the booster responses were all generally high and all subjects achieved similar percentages above predefined antibody titers, these differences are probably not clinically significant.

Antibodies, Bacterial↗
PubMed1999

Postmarketing evaluation of the safety and effectiveness of varicella vaccine.

BACKGROUND: The Oka strain of live attenuated varicella virus was licensed for use in healthy children in the United States in March, 1995. We report a postmarketing evaluation of the short term safety of this vaccine within Kaiser Permanente. METHODS: After licensure varicella vaccination was introduced into the preventive care program of the Northern California Kaiser Permanente Medical Care Program. Potential adverse events after vaccination with varicella vaccine were identified from automated clinical databases of hospitalizations, emergency room visits and clinic visits. Deaths were identified from automated clinical databases at Kaiser as well as from the State death records for California. To evaluate safety, rates of diagnosis-specific events in the risk periods were compared with the rates of such diagnosis-specific events in two self control and one historical control period. RESULTS: During the study period of April 1, 1995, to December 31, 1996, a total of 89753 adults and children received varicella vaccine. A total of 3200 relative risks were calculated, and of these 5 hospital diagnostic categories, 9 emergency visit diagnostic categories and 30 outpatient diagnostic categories demonstrated at least 1 relative risk with a P value of <0.05 in 1 or more age groups and in comparisons with 1 control period or more. The p value for these tests was not adjusted for multiple comparisons. Of these categories 14 demonstrated an increased risk either in more than 1 age group or against more than 1 comparison group. These categories included elective procedures, febrile seizure, febrile illness, well child, acute gastroenteritis, varicella, congenital anomaly, "rule out sepsis," trauma, viral syndrome, apnea, back pain, congenital valvular heart disease and vision evaluation for glasses. Of these the outcomes of elective procedure, congenital anomaly, congenital valvular heart disease, well child and vision evaluation for glasses were judged not to have a biologically plausible association with vaccination. A second diagnostic grouping included febrile illness, viral illness, febrile seizure and "rule out sepsis." In an analysis of these events which adjusted for the concomitant administration of M-M-R(II) vaccine, none of the associations was statistically associated with receipt of varicella vaccine. The diagnostic category of "rule out sepsis" still had a relative risk of 1.95 with P = 0.02. None of the children in the "rule out sepsis" category had positive bacteriologic cultures from any other normally sterile site. Because of the large number of gastroenteritis cases, we reviewed a random sample of 100 exposed and 100 unexposed cases. From this review no consistent time association or clustering of any of these events was seen in the exposed follow-up time interval. Only gastroenteritis and negative evaluations for sepsis were thought to be possibly associated with receipt of varicella vaccine. Although there was a statistically significant increased risk over the entire 30 day-period, there was no clustering of these events within the 30-day window. CONCLUSION: In this study population of 89753 children and adults, the varicella vaccine (Oka strain, Merck) appeared to have a favorable safety profile. In addition rates of varicella-like rash and of breakthrough cases were both low and consistent with the rates observed in prelicensure studies.

Adult↗
PubMed1999

A natural chimeric yeast containing genetic material from three species.

The Saccharomyces sp. CID1 isolate (CBS 8614) and several other Saccharomyces sensu stricto yeasts were analysed for their mitochondrial and nuclear genes. The data show that Saccharomyces sp. CID1, found so far only in one location in Europe, is a natural hybrid between three different Saccharomyces yeast species. Two of them, Saccharomyces cerevisiae-like and Saccharomyces bayanus-like, are ubiquitous and contributed parts of the nuclear genome; the third, Saccharomyces sp. IFO 1802-like, which has been found only in Japan, contributed the mitochondrial DNA molecule. These data suggest that the yeast cell is able to accommodate, express and propagate genetic material that originates from different species, and the very existence of the resulting natural hybrids indicates that such hybrids are well adapted to their habitats.

Base Sequence↗
PubMed1999

Inactivation of MXR1 abolishes formation of dimethyl sulfide from dimethyl sulfoxide in Saccharomyces cerevisiae.

Dimethyl sulfide (DMS) is a sulfur compound of importance for the organoleptic properties of beer, especially some lager beers. Synthesis of DMS during beer production occurs partly during wort production and partly during fermentation. Methionine sulfoxide reductases are the enzymes responsible for reduction of oxidized cellular methionines. These enzymes have been suggested to be able to reduce dimethyl sulfoxide (DMSO) as well, with DMS as the product. A gene for an enzymatic activity leading to methionine sulfoxide reduction in Saccharomyces yeast was recently identified. We confirmed that the Saccharomyces cerevisiae open reading frame YER042w appears to encode a methionine sulfoxide reductase, and propose the name MXR1 for the gene. We found that Mxr1p catalyzes reduction of DMSO to DMS and that an mxr1 disruption mutant cannot reduce DMSO to DMS. Mutant strains appear to have unchanged fitness under several laboratory conditions, and in this paper I hypothesize that disruption of MXR1 in brewing yeasts would neutralize the contribution of the yeast to the DMS content in beer.

Dimethyl Sulfoxide↗
PubMed1999

Non-neoplastic mortality of European workers who produce man made vitreous fibres.

OBJECTIVE: To study mortality from non-neoplastic diseases among European workers who produce man made vitreous fibres (MMVF). METHODS: 11,373 male workers were studied, who were employed for at least 1 year in the production of rock or slag wool (RSW), glass wool (GW), and continuous filament (CF) in 13 factories from seven European countries. Workers were followed up from the beginning of production, between 1933 and 1950 to 1990-2 and contributed 256,352 person-years of observation. Standardised mortality ratios (SMRs) were calculated with national mortalities for reference; an internal exposure-response analyses based on multivariate Poisson regression models was also conducted. RESULTS: Mortality from bronchitis, emphysema, and asthma was not increased (SMR 1.03, 95% confidence interval (95% CI) 0.82 to 1.28). In RSW workers, there was no overall increase in mortality from non-malignant renal diseases (SMR 0.97, 95% CI 0.36 to 2.11), although there was the suggestion of an increase in risk with duration of employment. Mortality from ischaemic heart disease was not increased overall (SMR 1.03, 95% CI 0.96 to 1.11), but RSW and CF workers with > or = 30 years since first employment had a higher risk. RSW and CF workers showed an increased mortality from external causes, mainly motor vehicle accidents and suicide, which was higher among workers with a short duration of employment. CONCLUSIONS: Mortality from most non-neoplastic diseases does not seem to be related to employment in the MMVF industry. The results on mortality from ischaemic heart disease and non-malignant renal diseases, however, warrant further investigations.

Cause of Death↗
PubMed1999

A novel protein tag from herpes simplex virus type 1 DNA polymerase.

An epitope (HPOL) derived from the so-called thumb region of the herpes simplex virus type 1 DNA polymerase in combination with a monoclonal antibody (MAb 1051c) was tested for protein tagging. Using a conventional expression vector, a DNA cassette encoding the HPOL epitope was fused to the C-terminus of the dihydrofolate reductase (DHFR) gene such that the recombinant DHFR contained both a N-terminal HIS-tag and a C-terminal HPOL tag. Expression of recombinant DHFR in Escherichia coli cells was compared by Western blot analysis using either mouse RGS.HIS antibody or MAb 1051c. Immunostaining revealed that both antibodies reacted specifically with DHFR, but the detection sensitivity achieved with MAb 1051c was about 15-fold greater using a standard staining protocol. An HPOL antibody column was successfully applied for affinity purification of DHFR, demonstrating the usefulness of the HPOL epitope/MAb 1051c system for protein tagging, expression monitoring and purification of HPOL-tagged recombinant proteins.

Antibodies, Monoclonal↗
PubMed1999

Cancer incidence among European man-made vitreous fiber production workers.

OBJECTIVES: This study analyzed cancer incidence among man-made vitreous fiber workers. METHODS: A cancer incidence follow-up was conducted among 3685 rock-slag wool (RSW) and 2611 glass wool (GW) production workers employed for > or =1 year in Denmark, Finland, Norway, or Sweden, and the standardized incidence ratios (SIR) were calculated on the basis of national incidence rates. RESULTS: Overall cancer incidence was close to expectation. Lung cancer incidence was increased among the RSW [SIR 1.08, 95% confidence interval (95% CI) 0.85-1.36] and GW (SIR 1.28, 95% CI 0.91-1.74) workers. For both subcohorts, a trend was suggested for time since first employment (P-value for linear trend 0.1 and 0.2, respectively). Neither subcohort showed an association with employment during the early technological phase, when fiber exposure was high. The incidence of oral, pharyngeal, and laryngeal cancer was increased among the RSW (SIR 1.46, 95% CI 0.99-2.07) and the GW (SIR 1.41, 95% CI 0.80-2.28) subcohorts. Despite a trend in risk for these neoplasms among the GW workers with time since first employment, the lack of a positive relation with other indirect indicators of fiber exposure points against a causal interpretation. No association between RSW or GW exposure and the risk of other neoplasms was suggested. CONCLUSIONS: These lung cancer results are similar to those of a mortality study that included a larger number of factories. For other cancers there was no suggestion of an association with RSW or GW exposure.

Humans↗
PubMed1999

Orbital floor repair with titanium mesh screen.

BACKGROUND AND OBJECTIVES: Surgical repair of the acutely fractured orbit strives to restore appearance, preserve ocular and orbital function, and avoid enophthalmos or hypoglobus. Repair is achieved with autologous bone graft, synthetic substitutes, or both. The purpose of this article is to present an alternative procedure--use of implants, cut from a titanium mesh screen, without bone graft. METHOD AND MATERIALS: A total of 51 orbital floor fractures in 43 patients were repaired with titanium mesh screen implants. In three patients with bilateral orbital floor fractures repaired with titanium mesh, intraoperative symmetry was improved with bone graft added to the mesh on one side. RESULTS AND/OR CONCLUSIONS: Follow-up was available for 42 orbits in 35 patients and averaged 9 months. The transconjunctival approach with lateral canthotomy yielded better results than the subciliary approach, which often caused transient scleral show or ectropion. One patient underwent surgery for ectropion following a subciliary approach, and one patient developed a 4-mm enophthalmos. Routine bone grafting is unnecessary, even in large floor defects. Titanium mesh implants are a simple and reliable option for orbital floor repair.

Bone Transplantation↗
PubMed1998

HLA-DR4 (DRB1*0401) transgenic mice expressing an altered CD4-binding site: specificity and magnitude of DR4-restricted T cell response.

Optimum function of HLA-DR molecules in transgenic mice requires efficient interaction between the class II molecules on APCs and CD4 on T cells. Residues 110 and 139 of the second domain of class II molecules are considered to be critical for recognition of CD4. We generated an HLA-DR4beta(NT) transgene construct in which positions 110 and 139 were altered to resemble endogenous mouse H2 Abeta molecules. This construct was introduced into (B10 x SWR) embryos, and DR4beta(NT) transgenic mice were produced. The transgene was transferred into B10.RFB3 (Ebeta0 EalphaP) mice. The transgene-encoded DR4beta molecules paired with endogenous Ealpha chains to form stable DR4beta/Ealpha dimers expressed on the cell surface. The hybrid dimers showed similar Ag-binding specificity to HLA-DR4 molecules and positively selected CD4+ T cells in vivo. Immunization of HLA-DR4beta(NT) transgenic mice with DR4-restricted peptides induced T cell proliferation in vitro. While the purified T cells from DR4beta(NT) transgenic mice responded strongly to the HA(307-319) presented by M12C3 transfectants expressing altered DR4beta/Ealpha heterodimers, the response to the same peptides presented by transfectants expressing wild-type DR4beta/Ealpha molecules was substantially reduced. Taken together, these data confirmed in vitro studies on the importance of these residues in CD4-MHC class II interaction. The altered HLA-DR4beta transgenic mice were able to overcome the species barrier and generate efficient HLA-DR4-restricted CD4-specific immune responses. Thus, residues 110 and 139 were critical for the interaction of class II with CD4 T cells during thymic selection as well as peripheral immune responses.

Animals↗
PubMed1998

A geographic information system on the potential distribution and abundance of Fasciola hepatica and F. gigantica in east Africa based on Food and Agriculture Organization databases.

An adaptation of a previously developed climate forecast computer model and digital agroecologic database resources available from FAO for developing countries were used to develop a geographic information system risk assessment model for fasciolosis in East Africa, a region where both F. hepatica and F. gigantica occur as a cause of major economic losses in livestock. Regional F. hepatica and F. gigantica forecast index maps were created. Results were compared to environmental data parameters, known life cycle micro-environment requirements and to available Fasciola prevalence survey data and distribution patterns reported in the literature for each species (F. hepatica above 1200 m elevation, F. gigantica below 1800 m, both at 1200-1800 m). The greatest risk, for both species, occurred in areas of extended high annual rainfall associated with high soil moisture and surplus water, with risk diminishing in areas of shorter wet season and/or lower temperatures. Arid areas were generally unsuitable (except where irrigation, water bodies or floods occur) due to soil moisture deficit and/or, in the case of F. hepatica, high average annual mean temperature >23 degrees C. Regions in the highlands of Ethiopia and Kenya were identified as unsuitable for F. gigantica due to inadequate thermal regime, below the 600 growing degree days required for completion of the life cycle in a single year. The combined forecast index (F. hepatica+F. gigantica) was significantly correlated to prevalence data available for 260 of the 1220 agroecologic crop production system zones (CPSZ) and to average monthly normalized difference vegetation index (NDVI) values derived from the advanced very high resolution radiometer (AVHRR) sensor on board the NOAA polar-orbiting satellites. For use in Fasciola control programs, results indicate that monthly forecast parameters, developed in a GIS with digital agroecologic zone databases and monthly climate databases, can be used to define the distribution range of the two Fasciola species, regional variations in intensity and seasonal transmission patterns at different sites. Results further indicate that many of the methods used for crop productivity models can also be used to define the potential distribution and abundance of parasites.

Africa, Eastern↗
PubMed1998

A common-sense climate index: is climate changing noticeably?

We propose an index of climate change based on practical climate indicators such as heating degree days and the frequency of intense precipitation. We find that in most regions the index is positive, the sense predicted to accompany global warming. In a few regions, especially in Asia and western North America, the index indicates that climate change should be apparent already, but in most places climate trends are too small to stand out above year-to-year variability. The climate index is strongly correlated with global surface temperature, which has increased as rapidly as projected by climate models in the 1980s. We argue that the global area with obvious climate change will increase notably in the next few years. But we show that the growth rate of greenhouse gas climate forcing has declined in recent years, and thus there is an opportunity to keep climate change in the 21st century less than "business-as-usual" scenarios.

Climate↗
PubMed1998

Vitamin A and cancer prevention I: observations in workers previously exposed to asbestos at Wittenoom, Western Australia.

Our aim was to describe a vitamin A-based cancer prevention program for former asbestos workers and to check for possible harmful effects by comparing rates of disease and death in study subjects with subjects who chose not to join. All subjects had been occupationally exposed to crocidolite at Wittenoom Gorge between 1943 and 1966; 1,677 subjects indicated interest in the program and 1,203 joined between June 1990 and May 1995. Comparison subjects consisted of 996 former workers known to be alive in Western Australia in 1990 who did not join the program. Program subjects were provided with annual supplies of vitamin A (either synthetic beta-carotene or retinol), help in quitting smoking and dietary advice. The comparison group received only mail contact. Both groups were followed up to December 1994 for vital status and cancer information, and rates of cancer and death from various causes were compared. Mortality in both groups was higher than expected (standardised mortality ratio 1.23 in program subjects and 1.67 in comparison subjects). After adjustment for age, smoking and asbestos exposure, the relative rates in participants compared with non-participants was below I for all examined cancers and causes of death. For mesothelioma and lung cancer, group differences increased with time from entry, whereas other differences dissipated with time. No significant side effects were reported. In conclusion, program participants had significantly lower mortality than non-participants, but the rates of the 2 groups converged with time.

Adult↗
PubMed1998

Vitamin A and cancer prevention II: comparison of the effects of retinol and beta-carotene.

Former blue asbestos workers known to be at high risk of asbestos-related diseases, particularly malignant mesothelioma and lung cancer, were enrolled in a chemo-prevention program using vitamin A. Our aims were to compare rates of disease and death in subjects randomly assigned to beta-carotene or retinol. Subjects were assigned randomly to take 30 mg/day beta-carotene (512 subjects) or 25,000 IU/day retinol (512 subjects) and followed up through death and cancer registries from the start of the study in June 1990 till May 1995. Comparison between groups was by Cox regression in both intention-to-treat analyses and efficacy analyses based on treatment actually taken. Median follow-up time was 232 weeks. Four cases of lung cancer and 3 cases of mesothelioma were observed in subjects randomised to retinol and 6 cases of lung cancer and 12 cases of mesothelioma in subjects randomised to beta-carotene. The relative rate of mesothelioma (the most common single cause of death in our study) for those on retinol compared with those on beta-carotene was 0.24 (95% CI 0.07-0.86). In the retinol group, there was also a significantly lower rate for death from all causes but a higher rate of ischaemic heart disease mortality. Similar results were found with efficacy analyses. Our results confirm other findings of a lack of any benefit from administration of large doses of synthetic beta-carotene. The finding of significantly lower rates of mesothelioma among subjects assigned to retinol requires further investigation.

Adult↗
PubMed1998

Beginning readers' use of orthographic analogies in word reading.

This research re-investigated the claim that beginning readers exploit information from the orthographic rime of clue words to help them to decode unfamiliar words. In Experiment 1, first-grade children were equally able to use orthographic information from the beginning, middle, and end of clue words to identify unfamiliar target words. Moreover, the improvement in reading end-(or orthographic rime-) same target words following clue word presentation reflected phonological priming. In second-grade children, with correction for retesting effects, improvement following clue word presentation for end-same and beginning-same target words was equivalent, although end-same target words improved more than middle-same target words. In Experiment 2, both first- and second-grade children were able to use orthographic information from the beginning, middle, and end of clue words to identify unfamiliar words. Clue word presentation enhanced the reading of beginning-same and end-same target words more than middle-same target words. Improvement was the same for beginning-same and end-same target words. Target word improvement following clue word presentation was greater than that for phonologically primed words only in children reading target words sharing the beginning sequence of the clue word.

Age Factors↗