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Biomedical subjects

J Hansen

Publications and source records attributed to J Hansen.

At least 55 records · Page 3Linked to original sources

Elevated risk for male breast cancer after occupational exposure to gasoline and vehicular combustion products.

BACKGROUND: Automotive gasoline contains benzene, 1,3-butadiene, 1, 2-dibromoethane and 1,2-dichloroethane, and the combustion products include certain polycyclic aromatic hydrocarbons, all of which have shown mammary gland carcinogenicity in long-term bioassays. It is the aim of this paper to investigate whether men occupationally exposed to gasoline and its combustion products have an elevated risk of breast cancer. METHODS: A nationwide register based case control study on male breast cancer morbidity was established among members of a pension fund, compulsory for all employees. Employment histories were reconstructed for each of 230 cases and 12,880 control subjects based on computerized records. The odds ratios, adjusted for socioeconomic status, were estimated by conditional logistic regression analysis. RESULTS: When a lag time of at least 10 years was included, the odds ratio for breast cancer among men with over three months of employment in trades with potential exposure to gasoline and combustion products was 2.5 (95% confidence interval: 1.3-4.5). Among men younger than 40 years at the time of first employment, the odds ratio was 5.4 (2.4-11.9). CONCLUSIONS: This study supports the hypothesis that occupational exposure to gasoline vapors and combustion products may play a role in the causation of male breast cancer. This hypothesis warrants further evaluation particularly in women.

Adult↗

[Überleben in der Kälte - wie Pflanzen sich vor Froststress schützen]

Kälte ist sowohl ein direkt, als auch indirekt wirkender Umweltfaktor, der die Produktivität und die Verbreitung von Pflanzen erheblich einschränkt. Besondere Schutzmechanismen ermöglichen es überwinternden Pflanzen, Frosttemperaturen während der kalten Jahreszeit ohne größere Schäden zu überstehen. Während der Anpassung an tiefe Temperaturen kommt es zur Umstellung des pflanzlichen Stoffwechsels und zu Veränderungen in der Ultrastruktur der Zelle.

Journal Article↗

The pYC plasmids, a series of cassette-based yeast plasmid vectors providing means of counter-selection.

A series of 24 general-purpose yeast plasmid vectors has been constructed. The plasmid series is composed of inter-replaceable cassettes, allowing for easy interconversion of plasmid types. In addition to the usual replication origins, selectable markers and multiple cloning sites (MCS), cassettes dedicated to counter-selection have been constructed. A pair of unique 8 bp restriction enzyme recognition sites flank each type of cassette, FseI in the case of yeast replication origins, AscI in the case of selectable markers, PacI in the case of counter-selectable markers and NotI in the case of the MCS. Thus, any given cassette can be replaced by another cassette of the same type, facilitating interconversion of any given plasmid from one type to another, even after the insertion of DNA into the MCS. Hence, the plasmids have been named pYC for 'yeast cassettes'. The cassettes consist of either NONE, CEN4/ARS or 2micro as replication origin, either URA3, MET2-CA (Lg-MET2) or the G418 resistance gene (the apt1 gene from bacterial transposon Tn903, encoding aminoglycoside phosphotransferase) as selectable markers, either NONE, PMET25-PKA3 or PCHA1-PKA3 as counter-selectable marker, and the MCS, containing recognition sites for AflII, AvrII, BspEI, PmeI, SacII, SalI, SunI, BamHI, EcoRI, HindIII, KpnI, MluI, NarI and SacI (of which the seven first are unique in all plasmids). The counter-selectable markers consist of the PKA3 gene under control of the conditional MET25 or CHA1 promoters. At activating conditions these promoters express the PKA3 gene at toxic levels, facilitating easy selection for loss of plasmid or 'loop-out' of plasmid DNA sequence after genomic integration.

Base Sequence↗

Computed chest tomography in an animal model for decompression sickness: radiologic, physiologic, and pathologic findings.

This study was conducted to investigate the early pulmonary effects of acute decompression in an animal model for human decompression sickness by CT and light microscopy. Ten test pigs were exposed to severe decompression stress in a chamber dive. Three pigs were kept at ambient pressure to serve as controls. Decompression stress was monitored by measurement of pulmonary artery pressure and arterial and venous Doppler recording of bubbles of inert gas. Chest CT was performed pre- and postdive and in addition the inflated lungs were examined after resection. Each lung was investigated by light microscopy. Hemodynamic data and bubble recordings reflected severe decompression stress in the ten test pigs. Computed tomography revealed large quantities of ectopic gas, predominantly intravascular, in three of ten pigs. These findings corresponded to maximum bubble counts in the Doppler study. The remaining test pigs showed lower bubble grades and no ectopic gas by CT. Sporadic interstitial edema was demonstrated in all animals--both test and control pigs--by CT of resected lungs and on histologic examination. A severe compression-decompression schedule can liberate large volumes of inert gas which are detectable by CT. Despite this severe decompression stress, which led to venous microembolism, CT and light microscopy did not demonstrate changes in lung structure related to the experimental dive. Increased extravascular lung water found in all animals may be due to infusion therapy.

Acute Disease↗

Cysteine is essential for transcriptional regulation of the sulfur assimilation genes in Saccharomyces cerevisiae.

Transcription of the genes for sulfur assimilation and methionine biosynthesis in Saccharomyces cerevisiae is regulated by the size of the intracellular pool of an organic sulfur compound. The identity of this compound is not clear, but suggestions include S-adenosylmethionine (SAM) and cysteine. By studying the repression of selected sulfur assimilation (MET) genes, we found that the ability to form cysteine from homocysteine is crucial for methionine-mediated repression to take place. The transcription of MET14 and MET25 could not be repressed by methionine in strains in which either STR4 (which encodes cystathionine beta-synthase) or STR1 (cystathionine gamma-lyase) was disrupted, whereas the repression was independent of GSH1 (which encodes the enzyme responsible for the first step in glutathione biosynthesis from cysteine). In contrast, cysteine could repress the MET genes in all of these strains. Two genes that presumably encode cystathionine gamma-synthase and cystathionine beta-lyase were identified by genetic disruption (ORFs YJR130c and YGL184c), yielding yeast strains that cannot convert cysteine into homocysteine. Repression by cysteine was possible in either disruptant, suggesting a role in repression for cysteine alone. While some repression of MET genes could be accomplished by homocysteine in a strain that cannot form SAM from methionine, a low intracellular level of SAM seems to be necessary for full cysteine-mediated repression to take place.

Blotting, Northern↗

Linkage and LOH studies in 19 cylindromatosis families show no evidence of genetic heterogeneity and refine the CYLD locus on chromosome 16q12-q13.

Familial cylindromatosis is an autosomal dominant predisposition to multiple neoplasms of the skin appendages. The susceptibility gene has previously been mapped to chromosome 16q12-q13 and has features of a recessive oncogene/tumour suppressor gene. We have now evaluated 19 families with this disease by a combination of genetic linkage analysis and loss of heterozygosity in cylindromas from affected individuals. All 15 informative families show linkage to this locus, providing no evidence for genetic heterogeneity. Recombinant mapping has placed the gene in an interval of approximately 1 Mb. There is no evidence, between families, of haplotype sharing that might be indicative of common founder mutations.

Carcinoma, Adenoid Cystic↗

Characterization of human RNA splice signals by iterative functional selection of splice sites.

An iterative in vitro splicing strategy was employed to select for optimal 3' splicing signals from a pool of pre-mRNAs containing randomized regions. Selection of functional branchpoint sequences in HeLa cell nuclear extract yielded a sequence motif that evolved from UAA after one round of splicing toward a UACUAAC consensus after seven rounds. A significant part of the selected sequences contained a conserved AAUAAAG motif that proved to be functional both as a polyadenylation signal and a branch site in a competitive manner. Characterization of the branchpoint in these clones to either the upstream or downstream adenosines of the AAUAAAG sequence revealed that the branching process proceeded efficiently but quite promiscuously. Surprisingly, the conserved guanosine, adjacent to the common AAUAAA polyadenylation motif, was found to be required only for polyadenylation. In an independent experiment, sequences surrounding an optimal branchpoint sequence were selected from two randomized 20-nt regions. The clones selected after six rounds of splicing revealed an extended polypyrimidine tract with a high frequency of UCCU motifs and a highly conserved YAG sequence in the extreme 3' end of the randomized insert. Mutating the 3' terminal guanosine of the intron strongly affects complex A formation, implying that the invariant AG is recognized early in spliceosome assembly.

Base Sequence↗

A double-blind comparison of fluvoxamine versus placebo in the treatment of compulsive buying disorder.

Nondepressed outpatients with a compulsive buying disorder were recruited by advertisement and word of mouth for inclusion in a controlled treatment trial. Following a 1-week single-blind placebo washout, subjects were randomly assigned to fluvoxamine (n = 12) or placebo (n = 11). Subjects received fluvoxamine (up to 300 mg daily) or placebo for 9 weeks. There were few dropouts. Outcome measures included the Yale-Brown Obsessive-Compulsive Scale--Shopping Version (YBOCS-SV), three Clinical Global Impressions (CGI) ratings, the Hamilton Rating Scale for Depression (HRSD), and the Maudsley Obsessive-compulsive Inventory (MOI). At the conclusion of the trial, 50% of fluvoxamine recipients and 63.6% of placebo recipients achieved CGI ratings of "much" or "very much" improvement, while 33% of fluvoxamine recipients were "very much" improved compared with 18% of placebo recipients (by endpoint analysis). Subjects in both treatment cells showed improvement as early as the second week of the trial, and for most, improvement continued during the 9-week study. There were no significant differences between fluvoxamine- and placebo-treated subjects on any of the outcome measures, with the exception that fluvoxamine recipients achieved greater improvement than placebo recipients on the MOI (p = .02). Adverse experiences were more frequent in the group receiving fluvoxamine, particularly nausea, insomnia, decreased motivation, and sedation. We conclude that in a short-term treatment trial of compulsive buying, subjects receiving fluvoxamine or placebo respond similarly.

Adult↗

Identification of the familial cylindromatosis tumour-suppressor gene.

Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).

Amino Acid Sequence↗

Metabolic modulation of sympathetic vasoconstriction in exercising skeletal muscle.

The tight coupling of oxygen supply and utilization in exercising skeletal muscle is the result of complex interactions between local mechanisms that control muscle blood flow and substrate utilization and systemic mechanisms that control cardiac output and arterial pressure. The role of the sympathetic nervous system in the integration of these responses, specifically the interaction between sympathetic activation and local vasodilator mechanisms in exercising muscle, has been an active area of research for many years yet remains incompletely understood. The functional consequence of sympathetic activation in exercising skeletal muscle has been the subject of considerable debate. Previous studies in animals and humans have suggested that sympathetic vasoconstricton in active muscle is (a) well maintained and serves to limit active hyperaemia, thereby preventing muscle blood flow from outstripping cardiac output in order to preserve blood pressure and vital organ perfusion or (b) greatly attenuated in order to optimize muscle perfusion, a concept that has been termed 'functional sympatholysis'. Studies performed over the past 70 years have provided conflicting evidence regarding the relative importance of sympathetic vasoconstriction vs. functional sympatholysis in exercising skeletal muscle. The focus of this review is mainly on recent studies in anaesthetized animal preparations and in conscious humans that have provided evidence for the metabolic modulation of sympathetic vasoconstriction in contracting skeletal muscle and have identified a number of key underlying mechanisms that extend the initial concept of sympatholysis.

Animals↗

Eradication of Helicobacter pylori compared with long-term acid suppression in duodenal ulcer disease. A randomized trial with 2-year follow-up. The Danish Ulcer Study Group.

BACKGROUND: Trials evaluating long-term management of duodenal ulcer disease have mainly been focused on recurrence of ulcers, disregarding effects on dyspeptic and reflux symptoms. Profound acid inhibition with a proton pump inhibitor is the gold standard therapy in acid-related diseases. We aimed to compare the symptomatic effects of eradication therapy with those of long-term omeprazole treatment in a design with periods both with and without acid inhibition. METHODS: Patients with active duodenal ulcer were randomized either to omeprazole, 20 mg twice daily until healing, followed by omeprazole, 20 mg/ day for 1 year, or to eradication therapy (metronidazole, amoxicillin, and omeprazole for 2 weeks) followed by placebo for 1 year. All patients were followed up passively for an additional year. Clinical controls were performed every 2 months the 1st year (maintenance phase) and every 6 months during the passive follow-up phase. The study was multicentric and double-blind. The primary end-point was discontinuation of treatment, irrespective of reason. RESULTS: Two hundred and seventy-six patients were randomized (139 in the eradication treatment group). In the maintenance phase there were no differences in the reporting of dyspeptic symptoms or in premature withdrawal. In the passive follow-up phase only five patients in the eradication therapy group discontinued owing to relapse of dyspeptic symptoms or ulcer, compared with 51 patients initially randomized to long-term omeprazole. There were no differences in reflux symptoms or in the development of reflux oesophagitis. CONCLUSIONS: Eradication therapy and long-term omeprazole are equally effective in controlling dyspeptic symptoms and reflux in duodenal ulcer patients with healed ulcers. One-quarter of the duodenal ulcer patients who start eradication therapy continue to be symptomatic or fail therapy for other reasons over a 2-year period. Eradication therapy does not increase the risk of reflux in ulcer patients.

Amoxicillin↗

Evaluation of new sclerotic bone metastases in breast cancer patients during treatment.

PURPOSE: According to the World Health Organization (WHO) criteria for response of bone metastases to therapy, new lesions indicate progressive disease. We intended to prove that a new sclerotic lesion on conventional radiography may also be a sign of a positive therapeutic response in a previously undetectable lytic metastasis. MATERIAL AND METHODS: In a previous placebo-controlled clinical trial of clodronate (Ostac) therapy, 139 breast cancer patients with bone metastases underwent both conventional radiography and bone scan every 6 months for 2 years with 99mTc before and during clodronate treatment. WHO criteria were applied for therapy response evaluation. RESULTS: In 24 patients, 52 new sclerotic lesions observed during therapy were selected for re-evaluation of conventional radiographs and bone scans. In 8 of the 24 patients, 17 of 52 new sclerotic lesions (33%) had showed positive uptake on previous bone scans. These lesions were possibly misinterpreted as new when applying WHO criteria. CONCLUSION: For better assessment of new sclerotic lesions during treatment, more sensitive techniques, e.g. bone scan, are needed as a complement to conventional radiography.

Adult↗

Offspring sex ratio of subfertile men and men with abnormal sperm characteristics.

Previous work has suggested an association between male subfertility and a female-biased offspring sex ratio. This study of the reproduction of men who had a semen analysis at the Sperm Analysis Laboratory in Copenhagen in the period 1963-1993 showed that the subfertile men had an offspring sex ratio as expected (51.0% boys versus 51.3%, P: = 0.56), and within the cohort, the offspring sex ratio had no material association with particular semen characteristics. Our results thus suggest that no important association exists between general male subfertility and a female-biased offspring sex ratio.

Cohort Studies↗

Fertility and offspring sex ratio of men who develop testicular cancer: a record linkage study.

Analysis of associations between testicular cancer, subfertility and offspring sex ratio (proportion of males born among newborns) was performed on 3530 Danish men, born 1945-1980, who developed testicular cancer in the period 1960-1993. As the basis of comparison we used the total population of Danish men born in the period 1945-1980 (n = 1 488 957) and their biological children (n = 1 250 989). Men who developed testicular cancer had, prior to the cancer diagnosis, a reduced fertility (standardized fertility rate ratio: 0.93, 95% confidence interval: 0.89-0.97) and a significantly lower proportion of boys (48.9%, P: = 0.02) compared with the general population (51.3%). The reduction in fertility was more pronounced in men with non-seminoma but the reduction in offspring sex ratio was independent of histological type. This confirms earlier results from less conclusive studies and indicates that testicular cancer, male subfertility and a female-biased sex ratio among new-born infants are characteristics of male reproduction that are linked by biological mechanisms.

Adult↗

A retrospective analysis of temporomandibular joint reconstruction with free fibula microvascular flap.

OBJECTIVES: The temporomandibular joint is occasionally encountered in extirpative surgery of the head and neck. It presents a difficult management issue. Little has been reported on functional outcomes after resection and reconstruction of the temporomandibular joint. DESIGN: A retrospective analysis consisting of chart reviews and phone interviews was performed on 17 patients who underwent fibular free flap reconstruction of the temporomandibular joint from 1993 to 1998. RESULTS: Mean follow-up in surviving patients (10) was 41.3 months. Mean age of the group was 62; male-to-female ratio was 11:6. Average hospital stay was 11.6 days. Four patients had no radiation therapy, 2 had preoperative and 11 had postoperative treatment. Five patients had one osteotomy, seven had two, one had three, and one had four. Ten patients could chew, one could not, and none were recorded for the remaining. Diet consisted of regular food for two patients, soft food for seven, full liquids for four, and tube feeds for four. Cosmesis was judged as excellent by eight patients, acceptable by two, and unacceptable by two. Five patients did not describe cosmesis. Most patients stated that bony contour was excellent, but that the soft tissue defect was noticeable. Speech was judged as intelligible by seven and moderately understandable by one. Nine patients did not describe speech. Two patients had postoperative displacement of the fibular head out of the fossa. CONCLUSION: Primary reconstruction of the temporomandibular joint with microvascular fibular flaps is a viable and effective means of restoring function. The majority of patients are able to resume oral feeds, obtain excellent or pleasing cosmetic results, and maintain intelligible speech.

Female↗

Pursestring closure of radial forearm fasciocutaneous donor sites.

BACKGROUND: The radial forearm fasciocutaneous free flap has become one of the most common methods of reconstructing defects after head and neck ablative surgery. The fasciocutaneous flap is an excellent replacement for the tissue that has been removed. Unfortunately, donor site morbidity remains a problem. Donor site morbidity is primarily related to poor skin graft take, cosmesis, and neural dysfunction. Decreasing the size of the donor site defect may allow for improved cosmesis with decreased morbidity. MATERIAL AND METHODS: Prospective evaluation of a pursestring closure of radial forearm fasciocutaneous donor sites over a 16-month period. RESULTS: Seventy-one radial forearm free flaps were used. Sixty-seven had a pursestring closure of the donor site. After flap elevation the mean size of the defect was 61 cm2 (range, 28-140 cm2). Pursestring closure decreased the mean of the defect to 34 cm2 (range, 10-104 cm2) (P <.0001). Defect size was decreased by a mean of 44.5% (range, 24.5%-66.7%) (P <.0001). COMPLICATIONS: The rate of skin graft loss (>25%) (9% of patients) was less than that reported in the literature. No patient required a second surgical procedure. Neural morbidity was equal in both groups. Cosmesis was much improved. CONCLUSIONS: Pursestring closure allowed for a significantly decreased donor defect, associated with better cosmesis and less skin graft loss.

Forearm↗

Nonlinear poisson-boltzmann theory of a wigner-seitz model for swollen clays

Swollen stacks of finite-size disclike Laponite clay platelets are investigated within a Wigner-Seitz cell model. Each cell is a cylinder containing a coaxial platelet at its center, together with an overall charge-neutral distribution of microscopic co and counterions, within a primitive model description. The nonlinear Poisson-Boltzmann (PB) equation for the electrostatic potential profile is solved numerically within a highly efficient Green's function formulation. Previous predictions of linearized Poisson-Boltzmann (LPB) theory are confirmed at a qualitative level, but large quantitative differences between PB and LPB theories are found at physically relevant values of the charge carried by the platelets. A hybrid theory treating edge effect at the linearized level yields good potential profiles. The force between two coaxial platelets, calculated within PB theory, is an order of magnitude smaller than predicted by LPB theory.

Journal Article↗

Genetic control of resistance to the sterol 14alpha-demethylase inhibitor fungicide prochloraz in the cereal eyespot pathogen Tapesia yallundae.

Sexual crosses were used to determine the genetic basis of resistance to the sterol 14 alpha-demethylase inhibitor fungicide prochloraz in the cereal eyespot pathogen Tapesia yallundae. Three different crosses between sensitive parental strains (22-432 and 22-433 [the concentration required to inhibit growth by 50% (IG(50)) for each was </=0.03 mg/liter]) and field isolates from France and New Zealand with differing levels of resistance (PR11 [IG(50) = 0.5 mg/liter], PR1 [IG(50) = 1.0 mg/liter], and 11-3-18 [IG(50) = 2.4 mg/liter]) yielded progeny showing a bimodal distribution, with an even number of sensitive and resistant progeny. This indicated the segregation of a single major gene for resistance in each cross, which was confirmed by the use of backcrosses, crosses between F(1) progeny, and control crosses between sensitive parents. However, there was also evidence of additional quantitative genetic components responsible for the increased IG(50)s of the more resistant isolates. A further cross was made between isolate PR11 and an F(1) progeny arising from isolate 11-3-18, and this also yielded progeny which were entirely prochloraz resistant. This suggested that resistance genes were allelic in these two isolates, with resistance conferred by a gene at the same locus (or closely linked loci), despite the fact that the isolates (PR11 and 11-3-18) originated from different continents.

Ascomycota↗