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J Hansen

Publications and source records attributed to J Hansen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Reliable short-term memory in the trion model: toward a cortical language and grammar.

It has previously been shown that Hebb learning in a single column in the trion model of cortical organization occurs by selection. Motivated by von Neumann's solution for obtaining reliability and by models of circulating cortical activity, we introduce Hebb intercolumnar couplings to achieve dramatic enhancements in reliability in the firing of connected columns. In order for these enhancements to occur, specific temporal phase differences must exist between the same inherent spatial-temporal memory patterns in connected columns. We then generalize the criteria of large enhancements in the global firing of the entire connected columnar network to investigate the case when different inherent memory patterns are in the columns. The spatial rotations as well as the temporal phases now are crucial. Only certain combinations of inherent memory patterns meet these criteria with the symmetry properties playing a major role. The columnar order of these memory patterns not in the same symmetry family can be extremely important. This yields the first higher-level architecture of a cortical language and grammar within the trion model. The implications of this result with regard to an innate human language and grammar are discussed.

Cerebral Cortex↗
PubMed2001

Tests to determine LC50 and discriminating doses for macrocyclic lactones against the cattle tick, Boophilus microplus.

Laboratory tests were carried out on larvae and adults of the cattle tick Boophilus microplus to determine the toxicity of macrocyclic lactone acaricides (MLs). Technical and commercial MLs were used in larval packet test (LPT), larval immersion test (LIT) and adult immersion test (AIT). In LIT and AIT the toxicity of MLs was much higher than for LPT. In the AIT, diluting the injectable formulation of MLs in water was as effective as dilution in ethanol+Triton X-100. LC50, LC99.9 and 95% confidence limits were determined so that a discriminating dose (DD) could be set for larval and adult tests in order to diagnose potential resistance to MLs in field samples of the tick. These DDs are for Australian strains of B. microplus and may not be suitable for other strains until further work is carried out. The value of these diagnostic tests can only be verified if or when resistance to MLs emerges in ticks.

Animals↗
PubMed2001

Increased breast cancer risk among women who work predominantly at night.

Irregular working hours, including working at night, have serious psychological and physiological effects. In a nationwide population-based case-control study, we investigated the breast cancer risk among 30- to 54-year-old Danish women who worked predominantly at night. Individual employment histories were reconstructed back to 1964 for each of 7035 women with breast cancer and their individually matched controls from the records of a nationwide pension scheme with compulsory membership. Odds ratios, including 5 years of induction time and adjusted for socio-economic status, age at the birth of first and last child and number of children, were estimated by conditional logistic regression analysis. The odds ratio for breast cancer among women who worked at night at least half of a year was 1.5 (95% confidence interval, 1.2 to 1.7), and there was a tendency to increasing odds ratio by increasing duration of nighttime employment.

Adult↗
PubMed2001

Postlicensure evaluation of the effectiveness of seven valent pneumococcal conjugate vaccine.

OBJECTIVE: To evaluate the impact of the introduction and routine use of seven valent pneumococcal conjugate vaccine on the epidemiology of invasive pneumococcal disease within the Northern California Kaiser Permanente (KP) population. METHODS: Surveillance for invasive pneumococcal disease has been in place within KP since 1995. Isolates from normally sterile sites in children are routinely sent for serotyping. Cases of invasive disease are identified through review of automated microbiology records within KP. Incidence rates of invasive disease were compared for the period before and after routine use of pneumococcal conjugate vaccine in children. RESULTS: The incidence of invasive pneumococcal disease caused by vaccine serotypes before the licensure and routine use of pneumococcal conjugate vaccine ranged between 51.52 and 98.15 cases per 100 000 person years in children <1 year of age and fell to 9.35 after introduction of vaccine. The incidence in children <2 years of age was 81.67 to 113.80 before introduction and 38.22 cases per 100 000 person years after introduction of the vaccine into the general population. These reductions in disease rates exceeded the average vaccine coverage substantially in each age group. No increase in disease incidence was observed for possibly cross-reacting serotypes or nonvaccine serotypes. CONCLUSION: The introduction and routine use of pneumococcal conjugate vaccine in our population have been associated with a substantial reduction in invasive disease incidence in children <5 years of age.

Child, Preschool↗
PubMed2001

Cancer incidence among Danish workers exposed to trichloroethylene.

Human evidence regarding the carcinogenicity of the animal carcinogen trichloroethylene (TCE) is limited. We evaluated cancer occurrence among 803 Danish workers exposed to TCE, using historical files of individual air and urinary measurements of TCE-exposure. The standardized incidence ratio (SIR) for cancer overall was close to unity for both men and women who were exposed to TCE. Men had significantly elevated SIRs for non-Hodgkin's lymphoma (SIR = 3.5; n = 8) and cancer of the esophagus (SIR = 4.2; n = 6). Among women, the SIR for cervical cancer was significantly increased (SIR = 3.8; n = 4). No clear dose-response relationship appeared for any of these cancers. We found no increased risk for kidney cancer. In summary, we found no overall increase in cancer risk among TCE-exposed workers in Denmark. For those cancer sites where excesses were noted, the small numbers of observed cases and the lack of dose-related effects hinder etiological conclusions.

Denmark↗
PubMed2001

Adeno-associated virus type 2-mediated gene transfer: role of cellular FKBP52 protein in transgene expression.

Although adeno-associated virus type 2 (AAV) has gained attention as a potentially useful vector for human gene therapy, the transduction efficiencies of AAV vectors vary greatly in different cells and tissues in vitro and in vivo. We have documented that a cellular tyrosine phosphoprotein, designated the single-stranded D-sequence-binding protein (ssD-BP), plays a crucial role in AAV-mediated transgene expression (K. Y. Qing, X.-S. Wang, D. M. Kube, S. Ponnazhagan, A. Bajpai, and A. Srivastava, Proc. Natl. Acad. Sci. USA 94:10879-10884, 1997). We have documented a strong correlation between the phosphorylation state of ssD-BP and AAV transduction efficiency in vitro as well as in vivo (K. Y. Qing, B. Khuntrirat, C. Mah, D. M. Kube, X.-S. Wang, S. Ponnazhagan, S. Z. Zhou, V. J. Dwarki, M. C. Yoder, and A. Srivastava, J. Virol. 72:1593-1599, 1998). We have also established that the ssD-BP is phosphorylated by epidermal growth factor receptor protein tyrosine kinase and that the tyrosine-phosphorylated form, but not the dephosphorylated form, of ssD-BP prevents AAV second-strand DNA synthesis and, consequently, results in a significant inhibition of AAV-mediated transgene expression (C. Mah, K. Y. Qing, B. Khuntrirat, S. Ponnazhagan, X.-S. Wang, D. M. Kube, M. C. Yoder, and A. Srivastava, J. Virol. 72:9835-9841, 1998). Here, we report that a partial amino acid sequence of ssD-BP purified from HeLa cells is identical to a portion of a cellular protein that binds the immunosuppressant drug FK506, termed the FK506-binding protein 52 (FKBP52). FKBP52 was purified by using a prokaryotic expression plasmid containing the human cDNA. The purified protein could be phosphorylated at both tyrosine and serine or threonine residues, and only the phosphorylated forms of FKBP52 were shown to interact with the AAV single-stranded D-sequence probe. Furthermore, in in vitro DNA replication assays, tyrosine-phosphorylated FKBP52 inhibited AAV second-strand DNA synthesis by greater than 90%. Serine- or threonine-phosphorylated FKBP52 caused approximately 40% inhibition, whereas dephosphorylated FKBP52 had no effect on AAV second-strand DNA synthesis. Deliberate overexpression of FKBP52 effectively reduced the extent of tyrosine phosphorylation of the protein, resulting in a significant increase in AAV-mediated transgene expression in human and murine cell lines. These studies corroborate the idea that the phosphorylation status of the cellular FKBP52 protein correlates strongly with AAV transduction efficiency, which may have important implications for the optimal use of AAV vectors in human gene therapy.

3T3 Cells↗
PubMed2001

Adeno-associated virus type 2-mediated gene transfer: altered endocytic processing enhances transduction efficiency in murine fibroblasts.

Adeno-associated virus type 2 (AAV) is a single-stranded-DNA-containing, nonpathogenic human parvovirus that is currently in use as a vector for human gene therapy. However, the transduction efficiency of AAV vectors in different cell and tissue types varies widely. In addition to the lack of expression of the viral receptor and coreceptors and the rate-limiting viral second-strand DNA synthesis, which have been identified as obstacles to AAV-mediated transduction, we have recently demonstrated that impaired intracellular trafficking of AAV inhibits high-efficiency transduction of the murine fibroblast cell line, NIH 3T3 (J. Hansen, K. Qing, H. J. Kwon, C. Mah, and A. Srivastava, J. Virol. 74:992-996, 2000). In this report, we document that escape of AAV from the endocytic pathway in NIH 3T3 cells is not limited but processing within endosomes is impaired compared with that observed in the highly permissive human cell line 293. While virions were found in both early and late endosomes or lysosomes of infected 293 cells, they were localized predominantly to the early endosomes in NIH 3T3 cells. Moreover, treatment of cells with bafilomycin A1 (Baf), an inhibitor of the vacuolar H(+)-ATPase and therefore of endosomal-lysosomal acidification, decreased the transduction of 293 cells with a concomitant decrease in nuclear trafficking of AAV but had no effect on NIH 3T3 cells. However, after exposure of NIH 3T3 cells to hydroxyurea (HU), a compound known to increase AAV-mediated transduction in general, virions were detected in late endosomes and lysosomes, and these cells became sensitive to Baf-mediated inhibition of transduction. Thus, HU treatment overcomes defective endocytic processing of AAV in murine fibroblasts. These studies provide insights into the underlying mechanisms of intracellular trafficking of AAV in different cell types, which has implications in the optimal use of AAV as vectors in human gene therapy.

3T3 Cells↗
PubMed2001

Arterial baroreflex control of sympathetic nerve activity during acute hypotension: effect of fitness.

We examined arterial baroreflex control of muscle sympathetic nerve activity (MSNA) during abrupt decreases in mean arterial pressure (MAP) and evaluated whether endurance training alters baroreflex function. Acute hypotension was induced nonpharmacologically in 14 healthy subjects, of which 7 were of high fitness (HF) and 7 were of average fitness (AF), by releasing a unilateral arterial thigh cuff after 9 min of resting ischemia under two conditions: control, which used aortic and carotid baroreflex (ABR and CBR, respectively) deactivation; and suction, which used ABR deactivation alone. The application of neck suction to counteract changes in carotid sinus transmural pressure during cuff release significantly attenuated the MSNA response (which increased 134 +/- 32 U/14 s) compared with control (which increased 195 +/- 43 U/14 s) and caused a greater decrease in MAP (19 +/- 2 vs. 15 +/- 2 mmHg; P < 0.05). Furthermore, during both trials, the HF subjects exhibited a greater decrease in MAP compared with AF subjects despite an augmented baroreflex control of MSNA. These data indicate that the CBR contributes importantly to the MSNA response during acute systemic hypotension. Additionally, we suggest that an impaired control of vascular reactivity hinders blood pressure regulation in HF subjects.

Adult↗
PubMed2000

No association of HIV-1 envelope (C2-V3-C3) sequence pattern with long-term nonprogression.

We previously identified a group of 10 long-term nonprogressors (LTNP) with HIV-1 infection. In this study, we have sequenced the envelope gene (C2-V3-C3) from the 10 LTNPs and from a control group of 9 people with rapidly progressing infection (RPI). The 19 individuals' CCR5 genotype and virus phenotype (i.e., syncytium-inducing/non-syncytium-inducing [SI/NSI]) were obtained from a previous study. A phylogenetic tree was constructed containing the 19 envelope sequences together with 42 local control env sequences obtained from other studies. Analysis of the phylogenetic tree did not reveal any relation between the envelope gene (C2-V3-C3) from LTNPs versus RPIs. When data from the CCR5 genotype and the virus phenotype were assembled in the phylogenetic tree, no significant clustering was observed. From alignment of the protein sequences, we found a possible N-glycan in position aa294 in env that was conserved in only 1 of 10 LTNPs; however, it was conserved in 6 of 9 RPIs. Our study could not demonstrate any association between LTNPs and the sequenced envelope gene segment (C2-V3-C3). This lack of association could be due to the relatively small sample size of the data set. Nor did we find any relation between the CCR5 genotype or the SI/NSI phenotype with the sequenced envelope genes from the 19 participants. The possible N-glycan position we have described is an interesting observation that may require further investigation.

Amino Acid Sequence↗
PubMed2000

Risk of testicular cancer in men with abnormal semen characteristics: cohort study.

OBJECTIVE: To explore the associations between semen characteristics and subsequent risk of testicular cancer. DESIGN: Cohort study. PARTICIPANTS: 32 442 men who had a semen analysis done at the Sperm Analysis Laboratory in Copenhagen during 1963-95. MAIN OUTCOME MEASURE: Standardised incidence ratios of testicular cancer compared with total population of Danish men. RESULTS: Men in couples with fertility problems were more likely to develop testicular cancer than other men (89 cases, standardised incidence ratio 1.6; 95% confidence interval 1.3 to 1.9). The risk was relatively constant with increasing time between semen analysis and cancer diagnosis. Analysis according to specific semen characteristics showed that low semen concentration (standardised incidence ratio 2.3), poor motility of the spermatozoa (2.5), and high proportion of morphologically abnormal spermatozoa (3.0) were all associated with an increased risk of testicular cancer. The only other cancer group that showed increased incidence was "peritoneum and other digestive organs" (six cases; 3.7, 1.3 to 8.0). Of these, two cases were probably and two cases were possibly extragonadal germ cell tumours. CONCLUSIONS: The results point towards the existence of common aetiological factors for low semen quality and testicular cancer. Low semen quality may also be associated with increased incidence of extragonadal germ cell tumours.

Adult↗
PubMed2000

GAP1, a novel selection and counter-selection marker for multiple gene disruptions in Saccharomyces cerevisiae.

We report on the use of a new homologous marker for use in multiple gene deletions in S. cerevisiae, the general amino acid permease gene (GAP1). A GAP1 strain can utilize L-citrulline as the sole nitrogen source but cannot grow in the presence of the toxic amino acid D-histidine. L-citrulline as well as D-histidine uptake is mediated solely by the general amino acid permease, and a gap1 strain is therefore able to grow in the presence of D-histidine but cannot utilize L-citrulline. Gene disruption is effected by transforming a gap1 strain with a gene cassette generated by PCR, containing GAP1 flanked by short (60 bp) stretches of the gene in question. Through homologous recombination, the cassette will integrate into the target gene, which is thus replaced by GAP1, and mutants are selected for on minimal L-citrulline medium. When propagated under non-selective conditions, some cells will lose the GAP1 gene. This is caused by recombination between two Ashbya gossypii AgLEU2 [corrected] direct repeats embracing GAP1, and will result in a sub-population of gap1 cells. Such cells are selected on a medium containing D-histidine, and may subsequently be used for a second gene disruption. Hence, multiple gene disruptions can be made fast, cheaply and easily in a gap1 strain, with two positive selection steps for each disruption.

Amino Acid Transport Systems↗
PubMed2000

Metabolic modulation of sympathetic vasoconstriction in human skeletal muscle: role of tissue hypoxia.

Sympathetically evoked vasoconstriction is modulated by skeletal muscle contraction, but the underlying events are incompletely understood. During contraction, intramuscular oxygenation decreases with increasing exercise intensity. We therefore hypothesized that tissue hypoxia plays a crucial role in the attenuation of sympathetic vasoconstriction in contracting skeletal muscle. In 19 subjects, near-infrared spectroscopy was used to measure decreases in muscle oxygenation (DeltatHbO2+MbO2) as an estimate of the vasoconstrictor response to reflex sympathetic activation with lower body negative pressure (LBNP) in the microcirculation of resting and contracting forearm muscles. Oxygen delivery to the muscles was reduced by decreasing (a) arterial O2 content by breathing 10 % O2, or (b) muscle perfusion by applying forearm positive pressure (FPP, +40 mmHg). In resting forearm, reflex sympathetic activation decreased muscle oxygenation by 11 +/- 1 %. Handgrip alone at 5 and 20 % of maximal voluntary contraction (MVC) decreased muscle oxygenation by 4 +/- 1 and 28 +/- 4 %, respectively. When superimposed on handgrip, LBNP-induced decreases in muscle oxygenation were preserved during handgrip at 5 % MVC, but were abolished during handgrip at 20 % MVC. Oral administration of aspirin (1 g) did not restore the latter response. When the decrease in forearm muscle oxygenation elicited by handgrip at 20 % MVC was mimicked by either (a) systemic hypoxia plus 5 % handgrip (DeltatHbO2+MbO2, -32 +/- 3 %), or (b) hypoperfusion of resting muscle by FPP (DeltatHbO2+MbO2, -26 +/- 6 %), LBNP-induced decreases in muscle oxygenation were greatly attenuated. These data suggest that local tissue hypoxia is involved in the metabolic attenuation of sympathetic vasoconstriction in the microcirculation of exercising human skeletal muscle. The specific underlying mechanism remains to be determined, although products of the cyclo-oxygenase pathway do not appear to be involved.

Adult↗
PubMed2000

Global warming in the twenty-first century: an alternative scenario.

A common view is that the current global warming rate will continue or accelerate. But we argue that rapid warming in recent decades has been driven mainly by non-CO(2) greenhouse gases (GHGs), such as chlorofluorocarbons, CH(4), and N(2)O, not by the products of fossil fuel burning, CO(2) and aerosols, the positive and negative climate forcings of which are partially offsetting. The growth rate of non-CO(2) GHGs has declined in the past decade. If sources of CH(4) and O(3) precursors were reduced in the future, the change in climate forcing by non-CO(2) GHGs in the next 50 years could be near zero. Combined with a reduction of black carbon emissions and plausible success in slowing CO(2) emissions, this reduction of non-CO(2) GHGs could lead to a decline in the rate of global warming, reducing the danger of dramatic climate change. Such a focus on air pollution has practical benefits that unite the interests of developed and developing countries. However, assessment of ongoing and future climate change requires composition-specific long-term global monitoring of aerosol properties.

Aerosols↗
PubMed2000

The complete atomic structure of the large ribosomal subunit at 2.4 A resolution.

The large ribosomal subunit catalyzes peptide bond formation and binds initiation, termination, and elongation factors. We have determined the crystal structure of the large ribosomal subunit from Haloarcula marismortui at 2.4 angstrom resolution, and it includes 2833 of the subunit's 3045 nucleotides and 27 of its 31 proteins. The domains of its RNAs all have irregular shapes and fit together in the ribosome like the pieces of a three-dimensional jigsaw puzzle to form a large, monolithic structure. Proteins are abundant everywhere on its surface except in the active site where peptide bond formation occurs and where it contacts the small subunit. Most of the proteins stabilize the structure by interacting with several RNA domains, often using idiosyncratically folded extensions that reach into the subunit's interior.

Archaeal Proteins↗
PubMed2000

The structural basis of ribosome activity in peptide bond synthesis.

Using the atomic structures of the large ribosomal subunit from Haloarcula marismortui and its complexes with two substrate analogs, we establish that the ribosome is a ribozyme and address the catalytic properties of its all-RNA active site. Both substrate analogs are contacted exclusively by conserved ribosomal RNA (rRNA) residues from domain V of 23S rRNA; there are no protein side-chain atoms closer than about 18 angstroms to the peptide bond being synthesized. The mechanism of peptide bond synthesis appears to resemble the reverse of the acylation step in serine proteases, with the base of A2486 (A2451 in Escherichia coli) playing the same general base role as histidine-57 in chymotrypsin. The unusual pK(a) (where K(a) is the acid dissociation constant) required for A2486 to perform this function may derive in part from its hydrogen bonding to G2482 (G2447 in E. coli), which also interacts with a buried phosphate that could stabilize unusual tautomers of these two bases. The polypeptide exit tunnel is largely formed by RNA but has significant contributions from proteins L4, L22, and L39e, and its exit is encircled by proteins L19, L22, L23, L24, L29, and L31e.

Archaeal Proteins↗
PubMed2000

Dietary supplementation with highly purified eicosapentaenoic acid and docosahexaenoic acid does not influence PAI-1 activity.

Impaired fibrinolysis due to elevated levels of plasminogen activator inhibitor type 1 (PAI-1) is a risk factor for atherothrombotic disease. Many studies have reported a positive correlation between serum triglycerides and PAI-1 activity. Dietary intervention with very long n-3 fatty acids from marine sources is known to decrease serum triglycerides, but an adverse increase in PAI-1 activity has been reported in some studies. A double blind, placebo controlled study was conducted among 224 middle-aged (ages 36-56), healthy, non-smoking men in which the participants were randomly assigned to daily supplementation with 3.8 g eicosapentaenoic acid/d, 3.6 g docosahexaenoic acid/d, or 4.0 g corn oil/d (placebo) for 7 weeks. PAI-1 activity increased by 2.35+/-6.24 U/ml (28%), 1.15+/-6.74 U/ml (14%), and 1.33+/-5.64 U/ml (22%) during dietary supplementation with eicosapentaenoic acid, docosahexaenoic acid, and corn oil, respectively, but the changes were not significantly different between groups. There was no relationship between change in concentrations of serum triglycerides or phospholipid n-3 fatty acids and change in PAI-1 activity. At baseline, analysis was performed to investigate the influence of dietary lipids, blood lipids, and serum fatty acids on plasma concentrations of PAI-1 activity. Dietary intake of saturated fat correlated directly with PAI-1 both in crude analysis and after adjustment for age and body mass index (kg/m(2)). Furthermore, PAI-1 was associated with body mass index, apo-B100, serum triglycerides, and the concentration of n-6 polyunsaturated fatty acids in serum. In a multiple regression analysis, 21% of the variation in PAI-1 activity could be explained by these variables. Plasma PAI-1 activity did not correlate with dietary intake or serum concentrations of n-3 polyunsaturated fatty acids. In a review of 17 trials, including 935 subjects that assessed the effect of n-3 fatty acids on PAI-1 activity, an overall 17.7% increase in PAI-1 activity was estimated by n-3 supplementation. However, only two studies were able to demonstrate a significant increase in PAI-1 attributable to n-3 fatty acid supplementation. We conclude that there is no strong evidence for an unfavourable, clinically relevant effect of n-3 fatty acids on PAI-1 activity in plasma.

Adult↗
PubMed2000

Restenosis and clinical outcome in patients treated with amlodipine after angioplasty: results from the Coronary AngioPlasty Amlodipine REStenosis Study (CAPARES).

OBJECTIVES: Our intent was to investigate the effect of the dihydropyridine calcium channel blocker amlodipine on restenosis and clinical outcome in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Amlodipine has sustained vasodilatory effects and relieves coronary spasm, which may reduce luminal loss and clinical complications after PTCA. METHODS: In a prospective, double-blind design, 635 patients were randomized to 10 mg of amlodipine or placebo. Pretreatment with the study drug started two weeks before PTCA and continued until four months after PTCA. The primary angiographic end point was loss in minimal lumen diameter (MLD) from post-PTCA to follow-up, as assessed by quantitative coronary angiography (QCA). Clinical end points were death, myocardial infarction, coronary artery bypass graft surgery and repeat PTCA (major adverse clinical events). RESULTS: Angioplasty was performed in 585 patients (92.1%); 91 patients (15.6%) had coronary stents implanted. Follow-up angiography suitable for QCA analysis was done in 236 patients in the amlodipine group and 215 patients in the placebo group (per-protocol group). The mean loss in MLD was 0.30 +/- 0.45 mm in the amlodipine group versus 0.29 +/- 0.49 mm in the placebo group (p = 0.84). The need for repeat PTCA was significantly lower in the amlodipine versus the placebo group (10 [3.1%] vs. 23 patients [7.3%], p = 0.02, relative risk ratio [RR]: 0.45, 95% confidence interval [CI]: 0.22 to 0.91), and the composite incidence of clinical events (30 [9.4%] vs. 46 patients (14.5%), p = 0.049, RR: 0.65, CI: 0.43 to 0.99) within the four months follow-up period (intention-to-treat analysis). CONCLUSIONS: Amlodipine therapy starting two weeks before PTCA did not reduce luminal loss, but the incidence of repeat PTCA and the composite major adverse clinical events were significantly reduced during the four-month follow-up period after PTCA with amlodipine as compared with placebo.

Amlodipine↗