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Biomedical subjects

S Jensen

Publications and source records attributed to S Jensen.

At least 19 recordsLinked to original sources
PubMed2003

Concentrations of dioxins and other organochlorines (PCBs, DDTs, HCHs) in human milk from Seveso, Milan and a Lombardian rural area in Italy: a study performed 25 years after the heavy dioxin exposure in Seveso.

AIM: To investigate whether those who were exposed to high levels of the dioxin TCDD 25 years ago in Seveso, northern Italy still have higher than the expected levels of dioxins in their fat stores, and to investigate the concentrations of dioxins in the breast milk of mothers in Seveso and in two other regions in Italy. The load of vertically transmitted dioxins to the next generation, if being breastfed, was also investigated. METHODS: As there may be a synergistic effect of mixtures of organic chlorines, the concentrations of pesticides such as DDTs and PCBs have also been studied in the same human milk samples. Breast milk from 12 mothers from Seveso, Central Milan and a Lombardian village was collected for analysis during the first week and 1 and 3 mo after delivery. Individual samples were used for the analysis of pesticides and PCBs, whereas dioxins were analysed in pooled samples from all 12 mothers on each occasion. RESULTS: In human milk from Seveso, the TCDD concentration in fat calculated on a fresh weight basis was more than twice as high as the level in the other two regions, whereas the concentrations of investigated other toxins were lower in Seveso possible due to induction of the enzyme cytochrome P4501A, which means that the total level of dioxins was the same in all three locations. The congener profile, measured as mean toxic equivalency (TEQ) values, was the same in the Italian samples as previously reported from Stockholm. The calculations are based on the most recent WHO TCDD equivalency factors (TEF). The DDE concentration was higher in the samples from Milan than in the samples from the other two Italian regions, which may be due to the fact that, to a greater extent than in the other regions, Milanese food is imported from countries where DDT is still used as a pesticide. CONCLUSION: Twenty-five years after the dioxin catastrophe, human milk from mothers in Seveso has concentrations of the highly toxic dioxin congener TCDD that are more than twice as high as those in central Milan and a Lombardian village. This means that breastfed infants in Seveso still store an appreciable amount of TCDD in their body fat. The health consequences of this fact remain to be elucidated. The effect of the high load of DDTs in central Milan also has to be considered

Adult↗
PubMed2003

Continued improvement of clinical outcome and cost effectiveness following intravascular ultrasound guided PCI: insights from a prospective, randomised study.

OBJECTIVE: To investigate in a prospective randomised study both long term clinical effects and cost effectiveness of percutaneous coronary interventions (PCI) with or without intravascular ultrasound (IVUS) guidance. METHODS: 108 male patients with stable angina referred for PCI of a significant coronary lesion were randomly assigned to IVUS guided PCI or conventional PCI. Individual accumulated costs of the entire follow up period were calculated and compared in the randomisation groups. Effectiveness of treatment was measured by freedom from major adverse cardiac events. RESULTS: Cost effectiveness of IVUS guided PCI that was noted at six months was maintained and even accentuated at long term follow up (median 2.5 years). The cumulated cost level was found to be lower for the IVUS guided group, with a cumulated cost of &163 672 in the IVUS guided group versus &313 706 in the coronary angiography group (p = 0.01). Throughout the study, mean cost per day was lower in the IVUS guided PCI group (&2.7 v & 5.2; p = 0.01). In the IVUS group, 78% were free from major adverse cardiac events versus 59% in the coronary angiography group (p = 0.04) with an odds ratio of 2.5 in favour of IVUS guidance. CONCLUSION: IVUS guidance results in continued improvement of long term clinical outcome and cost effectiveness. The results of this study suggest that IVUS guidance may be used more liberally in PCI.

Adult↗
PubMed2002

Q2 evolution of the generalized Gerasimov-Drell-Hearn integral for the neutron using a 3He target.

We present data on the inclusive scattering of polarized electrons from a polarized 3He target at energies from 0.862 to 5.06 GeV, obtained at a scattering angle of 15.5 degrees. Our data include measurements from the quasielastic peak, through the nucleon resonance region, and beyond, and were used to determine the virtual photon cross-section difference sigma(1/2)-sigma(3/2). We extract the extended Gerasimov-Drell-Hearn integral for the neutron in the range of four-momentum transfer squared Q2 of 0.1-0.9 GeV2.

Journal Article↗
PubMed2002

Argus: a new instrument for the measurement of the stratospheric dynamical tracers, N2O and CH4.

We describe here a new instrument for the simultaneous, in situ measurement of the stratospheric tracer molecules, nitrous oxide (N2O) and methane (CH4). Argus is unique in its small size making it well suited for limited payload atmospheric research platforms. Argus employs second harmonic spectroscopy using tunable lead-salt diode lasers emitting in the mid-infrared. We first explain the Argus design philosophy followed by detailed descriptions of the instrument's optical, mechanical, and thermal sub-systems. Argus employs an in-flight calibration system providing real time calibrations and tightly constrained uncertainty estimates of the returned data. Data analysis is carried out using non-linear least-squares model fits to the acquired second harmonic spectra. A sampling of Argus data acquired on a recent stratospheric research campaign in the Arctic winter is presented.

Methane↗
PubMed2001

A novel role of the budding yeast separin Esp1 in anaphase spindle elongation: evidence that proper spindle association of Esp1 is regulated by Pds1.

In Saccharomyces cerevisiae, the metaphase-anaphase transition is initiated by the anaphase-promoting complex-dependent degradation of Pds1, whereby Esp1 is activated to promote sister chromatid separation. Although this is a fundamental step in the cell cycle, little is known about the regulation of Esp1 and how loss of cohesion is coordinated with movement of the anaphase spindle. Here, we show that Esp1 has a novel role in promoting anaphase spindle elongation. The localization of Esp1 to the spindle apparatus, analyzed by live cell imaging, is regulated in a manner consistent with a function during anaphase B. The protein accumulates in the nucleus in G2 and is mobilized onto the spindle pole bodies and spindle midzone at anaphase onset, where it persists into midanaphase. Association with Pds1 occurs during S phase and is required for efficient nuclear targeting of Esp1. Spindle association is not fully restored in pds1 mutants expressing an Esp1-nuclear localization sequence fusion protein, suggesting that Pds1 is also required to promote Esp1 spindle binding. In agreement, Pds1 interacts with the spindle at the metaphase-anaphase transition and a fraction remains at the spindle pole bodies and the spindle midzone in anaphase cells. Finally, mutational analysis reveals that the conserved COOH-terminal region of Esp1 is important for spindle interaction.

Anaphase↗
PubMed2001

Candidate gene isolation and comparative analysis of a commonly deleted segment of 7q22 implicated in myeloid malignancies.

Monosomy 7 and deletion of 7q are recurring abnormalities in malignant myeloid diseases. Here we extensively characterize an approximately 2-Mb commonly deleted segment (CDS) of 7q22 bounded by D7S1503 and D7S1841. Approximately 1.8 Mb of sequence have been generated from this interval, facilitating the construction of a transcript map that includes large numbers of genes and ESTs. The intron/exon organization of seven genes and expression patterns of three genes were determined, and leukemia samples were screened for mutations in five genes. We have used polymorphic markers from this region to examine leukemia cells for allelic loss within 7q22. Finally, we isolated mouse genomic clones orthologous to several of the characterized human genes. Fluorescence in situ hybridization studies using these clones indicate that a region of orthologous synteny lies on proximal mouse chromosome 5. These resources should greatly accelerate the pace of candidate gene discovery in this region.

Acute Disease↗
PubMed2001

Risk factors for age-related macular degeneration: Pooled findings from three continents.

OBJECTIVE: To assess the prevalence and potential risk factors for late age-related macular degeneration (AMD) in three racially similar populations from North America, Europe, and AUSTRALIA: DESIGN: Combined analysis of population-based eye disease prevalence data. PARTICIPANTS: There were 14,752 participants with gradable photographs from the Beaver Dam Eye Study (n = 4756), Rotterdam Study (n = 6411), and Blue Mountains Eye Study (n = 3585). MAIN OUTCOME MEASURES: AMD diagnosis was made from masked grading of stereo macular photographs. Final classification of AMD cases was agreed by consensus between study investigators. RESULTS: AMD prevalence was strongly age related. Overall, AMD was present in 0.2% of the combined population aged 55 to 64 years, rising to 13% of the population older than 85 years. Prevalence of neovascular AMD (NV) increased from 0.17% among subjects aged 55 to 64 years to 5.8% for those older than 85 years. Prevalence of pure geographic atrophy (GA) increased from 0.04% to 4.2% for these age groups. There were no significant gender differences in the prevalence of NV or GA. Subjects in the Rotterdam population had a significantly lower age-adjusted and smoking-adjusted risk of NV than subjects in the Beaver Dam and Blue Mountains populations. Apart from age, tobacco smoking was the only risk factor consistently associated with any form of AMD in all sites separately and in pooled analyses over the three sites. CONCLUSIONS: These combined data from racially similar communities across three continents provide strong and consistent evidence that tobacco smoking is the principal known preventable exposure associated with any form of AMD.

Adult↗
PubMed2001

Mec1p regulates Pds1p levels in S phase: complex coordination of DNA replication and mitosis.

Genetic evidence suggests that the securin Pds1p is the target of a late-S-phase checkpoint control. Here we show that Pds1p becomes essential once two-thirds of the genome has been replicated and that the coupling of the completion of genome replication with mitosis relies on the regulation of Pds1p levels. Mec1p is needed to maintain Pds1p levels under S-phase checkpoint conditions. In contrast, Rad53p and Chk1p, needed for the stabilization of Pds1p in the context of the G2 DNA-damage checkpoint pathway, are dispensable. Thus, the Pds1p-dependent late-S-phase checkpoint pathway couples replication with mitosis but is mechanistically distinct from the G2 DNA-damage checkpoint. Finally, we show that the inhibition of spindle elongation in early S phase, controlled by the Mec1p/Rad53p branch, is not regulated via Pds1p/Esp1p. This can mechanistically explain the need for branched S-phase checkpoint controls.

Cell Cycle Proteins↗
PubMed2001

Crystal structure and kinetic analysis of beta-lactamase inhibitor protein-II in complex with TEM-1 beta-lactamase.

The structure of the 28 kDa beta-lactamase inhibitor protein-II (BLIP-II) in complex with the TEM-1 beta-lactamase has been determined to 2.3 A resolution. BLIP-II is a secreted protein produced by the soil bacterium Streptomyces exfoliatus SMF19 and is able to bind and inhibit TEM-1 with subnanomolar affinity. BLIP-II is a seven-bladed beta-propeller with a unique blade motif consisting of only three antiparallel beta-strands. The overall fold is highly similar to the core structure of the human regulator of chromosome condensation (RCC1). Although BLIP-II does not share the same fold with BLIP, the first beta-lactamase inhibitor protein for which structural data was available, a comparison of the two complexes reveals a number of similarities and provides further insights into key components of the TEM-1-BLIP and TEM-1-BLIP-II interfaces. Our preliminary results from gene knock-out studies and scanning electron microscopy also reveal a critical role of BLIP-II in sporulation.

Amino Acid Sequence↗
PubMed2001

The Spo12 protein of Saccharomyces cerevisiae: a regulator of mitotic exit whose cell cycle-dependent degradation is mediated by the anaphase-promoting complex.

The Spo12 protein plays a regulatory role in two of the most fundamental processes of biology, mitosis and meiosis, and yet its biochemical function remains elusive. In this study we concentrate on the genetic and biochemical analysis of its mitotic function. Since high-copy SPO12 is able to suppress a wide variety of mitotic exit mutants, all of which arrest with high Clb-Cdc28 activity, we speculated whether SPO12 is able to facilitate exit from mitosis when overexpressed by antagonizing mitotic kinase activity. We show, however, that Spo12 is not a potent regulator of Clb-Cdc28 activity and can function independently of either the cyclin-dependent kinase inhibitor (CDKi), Sic1, or the anaphase-promoting complex (APC) regulator, Hct1. Spo12 protein level is regulated by the APC and the protein is degraded in G1 by an Hct1-dependent mechanism. We also demonstrate that in addition to localizing to the nucleus Spo12 is a nucleolar protein. We propose a model where overexpression of Spo12 may lead to the delocalization of a small amount of Cdc14 from the nucleolus, resulting in a sufficient lowering of mitotic kinase levels to facilitate mitotic exit. Finally, site-directed mutagenesis of highly conserved residues in the Spo12 protein sequence abolishes both its mitotic suppressor activity as well as its meiotic function. This result is the first indication that Spo12 may carry out the same biochemical function in mitosis as it does in meiosis.

Amino Acid Sequence↗
PubMed2001

Dosage suppressors of pds1 implicate ubiquitin-associated domains in checkpoint control.

In budding yeast, anaphase initiation is controlled by ubiquitin-dependent degradation of Pds1p. Analysis of pds1 mutants implicated Pds1p in the DNA damage, spindle assembly, and S-phase checkpoints. Though some components of these pathways are known, others remain to be identified. Moreover, the essential function of Pds1p, independent of its role in checkpoint control, has not been elucidated. To identify loci that genetically interact with PDS1, we screened for dosage suppressors of a temperature-sensitive pds1 allele, pds1-128, defective for checkpoint control at the permissive temperature and essential for viability at 37 degrees C. Genetic and functional interactions of two suppressors are described. RAD23 and DDI1 suppress the temperature and hydroxyurea, but not radiation or nocodazole, sensitivity of pds1-128. rad23 and ddi1 mutants are partially defective in S-phase checkpoint control but are proficient in DNA damage and spindle assembly checkpoints. Therefore, Rad23p and Ddi1p participate in a subset of Pds1p-dependent cell cycle controls. Both Rad23p and Ddi1p contain ubiquitin-associated (UBA) domains which are required for dosage suppression of pds1-128. UBA domains are found in several proteins involved in ubiquitin-dependent proteolysis, though no function has been assigned to them. Deletion of the UBA domains of Rad23p and Ddi1p renders cells defective in S-phase checkpoint control, implicating UBA domains in checkpoint signaling. Since Pds1p destruction, and thus checkpoint regulation of mitosis, depends on ubiquitin-dependent proteolysis, we propose that the UBA domains functionally interact with the ubiquitin system to control Pds1p degradation in response to checkpoint activation.

Amino Acid Sequence↗
PubMed2001

The Bub2-dependent mitotic pathway in yeast acts every cell cycle and regulates cytokinesis.

In eukaryotes an abnormal spindle activates a conserved checkpoint consisting of the MAD and BUB genes that results in mitotic arrest at metaphase. Recently, we and others identified a novel Bub2-dependent branch to this checkpoint that blocks mitotic exit. This cell-cycle arrest depends upon inhibition of the G-protein Tem1 that appears to be regulated by Bfa1/Bub2, a two-component GTPase-activating protein, and the exchange factor Lte1. Here, we find that Bub2 and Bfa1 physically associate across the entire cell cycle and bind to Tem1 during mitosis and early G1. Bfa1 is multiply phosphorylated in a cell-cycle-dependent manner with the major phosphorylation occurring in mitosis. This Bfa1 phosphorylation is Bub2-dependent. Cdc5, but not Cdc15 or Dbf2, partly controls the phosphorylation of Bfa1 and also Lte1. Following spindle checkpoint activation, the cell cycle phosphorylation of Bfa1 and Lte1 is protracted and some species are accentuated. Thus, the Bub2-dependent pathway is active every cell cycle and the effect of spindle damage is simply to protract its normal function. Indeed, function of the Bub2 pathway is also prolonged during metaphase arrests imposed by means other than checkpoint activation. In metaphase cells Bub2 is crucial to restrain downstream events such as actin ring formation, emphasising the importance of the Bub2 pathway in the regulation of cytokinesis. Our data is consistent with Bub2/Bfa1 being a rate-limiting negative regulator of downstream events during metaphase.

Anaphase-Promoting Complex-Cyclosome↗
PubMed2001

Reproductive toxicity in mink (Mustela vison) chronically exposed to environmentally relevant polychlorinated biphenyl concentrations.

Female mink were exposed to a technical polychlorinated biphenyl (PCB) preparation (Clophen A50 [A50]; 0.1 or 0.3 mg/animal/d), one fraction of A50 containing the non- and mono-ortho-chlorinated congeners (0-1-ortho-chlorobiphenyls [CBs]), another fraction of A50 containing the congeners with two to four ortho-chlorines (2-4-ortho-CBs), or an organic extract from Baltic gray seal blubber. The animals were exposed for 18 months, including two reproduction seasons. Among the animals given the highest dose of A50, the whelping frequency was reduced in the second reproductive season, and all kits died within 24 h of birth. Reproduction was also impaired by the lower dose of A50. Daily exposure to the 0-1-ortho-CBs separated from 0.3 mg A50 severely reduced kit survival. Reproduction was not significantly impaired by daily exposure to the 2-4-ortho-CBs separated from 0.3 mg A50 or by exposure to the blubber extract. We conclude that the reproductive toxicity in chronically PCB-exposed mink is caused by the aryl hydrocarbon (Ah) receptor agonists. The lowest-observed-effect level for reproductive impairment was 2.4 ng 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQs) per kilogram body weight and day (22 pg TEQs/g feed). Ethoxyresorufin-O-dealkylase (EROD) was strongly induced by the 0-1-ortho-CBs and pentoxyresorufin-O-dealkylase by the 2-4-ortho-CBs. High EROD activity was correlated with low kit production, and consequently EROD may serve as a marker for reproductive toxicity by Ah receptor agonists in mink.

Administration, Oral↗
PubMed2001

Musculoskeletal causes of chest pain.

BACKGROUND: Chest pain is a common presenting problem to general practitioners and accident and emergency departments. Such a symptom generates anxiety in both patients and their medical attendants, for fear that this symptom represents a life threatening event. Numerous investigations often ensue, adding to the physical and financial burden on an already stressed health system. Musculoskeletal causes of chest pain are common but frequently overlooked. OBJECTIVE: This article aims to outline some of the more common musculoskeletal problems which may present as chest pain, and to present a practical approach to their diagnosis and management. DISCUSSION: It is estimated that somewhere in the vicinity of 20-25% of noncardiac chest pain has a musculoskeletal basis. Careful history taking to identify red flag conditions differentiates those who require further investigation. Historical features suggesting a musculoskeletal cause include pain on specific postures or physical activities. A musculoskeletal diagnosis can usually be confirmed by clinical examination alone, the key to which is reproducing the patient's pain by either a movement or more specifically palpation over the structure that is the source of the pain. Confirming the diagnosis, explanation and reassurance allay anxiety. Management strategies include manual therapy, the provision of analgesia and anti-inflammatory agents, either topically, orally or by injection. Focal injection of local anaesthetic alone may also be a useful diagnostic and therapeutic tool.

Adult↗
PubMed2001

[Reconstruction of mental health services in Bosnia and Herzegovina].

Psychiatric services in Bosnia-Herzegovina before the war disaster was fairly developed and one of the best organized services amongst the republics of the former Yugoslavia. The psychiatric care system was based on psychiatric hospitals and small neuropsychiatric wards within general hospitals, accompanied by psychiatric services in health centers. The onset of war in B&H brought devastation and destruction in all domains of life, including the demolition and closing of numerous traditional psychiatric institutions, together with massive psychological suffering of the whole civilian population. Already during the war, and even more so after the war, the reconstruction and reorganization of the mental health services was undertaken. The basis of mental health care for the future is designed as a system where majority of services is located in the community, as close as possible to the habitat of the patients. The key aspect of the system of the comprehensive health care is primary health care and the main role is assigned to family practitioners and mental health professionals working in the community. Large psychiatric institutions were either closed or devastated, or have their capacities extensively reduced. There will be no reconstructions or reopening of the old psychiatric facilities, nor the new ones will be built. The most integrated part of the psychiatric system are the Community based mental health centers. Each of these centers will serve a particular geographic area. The centers will be responsible for prevention and treatment of psychiatric disorders, as well as for the mental health well being. Chronic mental health patients without families and are not able to independently live in the community will be accommodated in designated homes and other forms of protected accommodation within their communities. The principal change in mental health policy in B&H was a decision to transfer psychiatric services from traditional facilities into community, much closer to the patients. Basic elements of the mental health policy in B&H are: Decentralization and sectorization of mental health services; Intersectorial activity; Comprehensiveness of services; Equality in access and utilization of psychiatric service resources; Nationwide accessibility of mental health services; Continuity of services and care, together with the active participation of the community. This overview discusses the primary health care as the basic component of the comprehensive mental health care in greater detail, including tasks for family medicine teams and each individual member. 1. Comprehensive psychiatric care is implemented by primary health care physicians, specialized Centers for community-based mental health care, psychiatric wards of general hospitals and clinical centers in charge of brief, "acute" inpatient care; 2. Primary mental health care is implemented by family practitioners (primary care physicians) and their teams; 3. Specialized psychiatric care in community is performed professional teams specialized mental health issues' within Mental health centers in corresponding sectors; 4. A great deal of relevance is given to development of confidence and utilization of links between primary health care teams and specialized teams in Mental health centers and psychiatric in patient institutions; 5. Psychiatric wards within general cantonal hospitals, departments of psychiatric clinics in Sarajevo, Tuzla, and Mostar, and Cantonal Psychiatric hospital in Sarajevo (Jagomir) shall admit acute patients as well as chronic (with each new relapse). Treatment in these facilities is brief an patients are discharged to return to their homes, with further treatment referral to their family practitioner or designated Mental health center; 6. Chronic mental patients with severe residual impairment in social, psychological, and somatic functioning, shall live in the community with their families or independently. Those chronic patients without families and economic and other resources to live independently shall be placed in supervised Homes in the communities where they live. The above delineated strategy of mental health care program in B&H has several fundamental and specific objectives, among which the most important are: Reduction of incidence and prevalence of some mental disorders, particularly war stress-related disorders and suicide; Reduction of level of functional disability caused by mental disorders through improvement of treatment and care of individuals with mental health problems; Improvement of psychosocial well being of people with mental health problems, through implementation of comprehensive and accessible service for community mental health care; and Respect of basic human rights of individuals with mental health disabilities. The program has been updated since 1996, after the two-year pilot program. The main goals for current two- and five-year period are: Implement the mental health care reform program by launching all 38 Mental health centers in the Federation of BiH by 2002; Complete the 10-day education and re-education of at least 50% of all professionals employed in mental health services in FB&H by 2002; and Achieve that 80 percent of all mental health problems are treated by family medicine teams (primary care practitioners) and specialized mental health services (Community mental health care centers) by 2005.

Bosnia and Herzegovina↗
PubMed2000

Contribution of planar (0-1 ortho) and nonplanar (2-4 ortho) fractions of Aroclor 1260 to the induction of altered hepatic foci in female Sprague-Dawley rats.

The hepatic tumor promoting activity of the planar 0-1 ortho ( approximately 9.7% w/w) and the nonplanar 2-4 ortho ( approximately 90.3% w/w) fraction of the commercial PCB mixture Aroclor 1260 was studied using a medium-term two-stage initiation/promotion bioassay in female Sprague-Dawley rats. Fractionation was carried out on an activated charcoal column. The composition of the effluent from the column was tested by GC-ECD. The absence of planar compounds in the 2-4 ortho fraction was confirmed by GC-MS analysis. The dioxin-like toxic potency of the fractions was determined with the DR-CALUX assay. The animal experiment was started with the initiation procedure (diethylnitrosamine injection, 30 mg/kg body wt ip, 24 h after (2)/(3) hepatectomy), followed 6 weeks later by the promotion treatment, which consisted of a weekly subcutaneous injection during 20 weeks. Exposure groups (n = 10) received the following treatments (dose/kg body wt/week): Aroclor 1260 (10 mg), 0-1 ortho fraction (0.97 mg), 2-4 ortho fraction (1, 3, or 9 mg), a reconstituted 0-4 ortho fraction (9.97 mg), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153; 1 or 9 mg), 2,3,7,8-TCDD (1 microg; positive control) or corn oil (1 ml; vehicle control). One group did not receive a promotion treatment. All exposure groups exhibited a significantly increased volume fraction of the liver occupied by hepatic foci positive for the placental form of glutathione-S-transferase-p compared to the corn oil control, except for the groups treated with 0-1 ortho fraction and 1 mg PCB 153/kg body wt/week. Approximately 80% of the total tumor promoting capacity of the reconstituted 0-4 ortho fraction could be explained by the 2-4 ortho PCB fraction while the 0-1 ortho fraction had only a negligible contribution. These results suggest that the majority of the tumor promotion potential of PCB mixtures resides in the non-dioxin-like fraction, which is not taken into account in the toxic equivalency factor (TEF) approach for risk assessment of PCBs. This may result in an underestimation of the tumor promotion potential of environmental PCB mixtures.

Animals↗