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Biomedical subjects

O Nielsen

Publications and source records attributed to O Nielsen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Localization of E-cadherin in villous, extravillous and vascular trophoblasts during intrauterine, ectopic and molar pregnancy.

Previous reports have described down-regulation of E-cadherin in trophoblasts differentiating to an invasive phenotype. This study shows the localization of E-cadherin in a prospective design with stereological sampling of fetal and maternal first, second and third trimester tissue. E-cadherin was observed in villous cytotrophoblasts, and in non-proliferating, intermediate trophoblasts (IT) within cell columns and islands in intrauterine, ectopic and partial molar placentas. Highly proliferating IT with cytological atypia in complete molar placentas were also E-cadherin-positive. E-cadherin was present in trophoblasts throughout the anchoring cell columns. Trophoblasts undergoing epithelial mesenchymal transformation (EMT) detaching from the distal cell columns and deeper located single extravillous interstitial trophoblasts (EVT) showed E-cadherin-negative breaches in the cell membrane. Prior to the late second trimester, the relative number of E-cadherin-positive single EMT and EVT differed from the total number of cytokeratin-positive trophoblasts. Intraluminal, endovascular and perivascular trophoblasts adjacent to the maternal vessels were also E-cadherin-positive, but a highly varying pattern was observed at different ages of gestation. Our results indicate a temporary shift in E-cadherin expression in extravillous trophoblasts possessing a migrating and invasive potential. Functional E-cadherin may be restored as trophoblasts aggregate in the decidua and the vessel wall after completion of migration.

Antibodies, Monoclonal↗
PubMed2000

A morbillivirus antibody survey of Atlantic walrus, narwhal and beluga in Canada.

A longitudinal serologic survey was conducted for morbillivirus antibodies in Atlantic walruses (Odobenus rosmarus rosmarus), narwhal (Monodon monoceros), and beluga (Delphinapterus leucas) from the Northwest Territories, Nunavut and the St. Lawrence estuary (Canada). Sixty-five of 131 (50%) walruses sampled between 1984 and 1993 had detectable morbillivirus neutralizing antibodies. Positive walrus were identified from four of five Arctic sampling sites, to as far back as 1984. Prevalence of morbillivirus neutralizing antibodies in walruses from Foxe Basin ranged from a high of 76% (n = 21) in 1993 to a low of 22% (n = 28) in 1984. Limitations in sample acquisition may have produced underestimates for the 1984 data. There are no reports of clinical morbillivirus infection in walruses. Our results are consistent with the hypothesis that a morbillivirus similar or identical to phocine distemper virus (PDV) has circulated among walrus populations of the eastern Canadian Arctic, at least since the early 1980s. No narwhal (n = 79) or beluga (n = 445) from Arctic waters were identified as having antibodies to dolphin morbilivirus (DMV) above the threshold serum dilution of log2 4. Also, none of the beach-cast cetacean carcasses (n = 28) from the Gulf of St. Lawrence and the St. Lawrence estuary were positive for antibodies to DMV. This indicates that Gulf of St. Lawrence, St. Lawrence estuary, and Arctic cetaceans either have not been exposed to DMV or an antigenically related morbillivirus, or are not susceptible to infection.

Animals↗
PubMed2000

Brucellosis in ringed seals and harp seals from Canada. lforbes@em.agr.ca.

A novel Brucella sp. was isolated from lymph nodes of four ringed seals (Phoca hispida) collected near Pangnirtung (Baffin Island, Canada) in January and February 1995 and in one harp seal (Phoca groenlandica) collected near the Magdalen Islands (Gulf of St. Lawrence, Canada) in March 1996. Bacteriological characteristics were the same for all five isolates. The colonies were typical of Brucella spp., but took 2 to 5 days longer than the traditional species to appear on primary isolation media. Biotyping results did not match any of the known biovars of Brucella, but were similar to isolates of the genus Brucella previously reported from marine mammals inhabiting other areas of the northern hemisphere. This is the first confirmed report of brucellosis in marine mammals from Canada, and the first report of this organism in ringed and harp seals.

Animals↗
PubMed1999

Localization and significance of urokinase plasminogen activator and its receptor in placental tissue from intrauterine, ectopic and molar pregnancies.

Urokinase plasminogen activator receptor (uPAR) is a membrane-anchored protein with urokinase plasminogen activator (uPA) as the ligand. This complex induces proteolysis and remodelling of maternal decidua during placental implantation. The presence of uPAR on trophoblasts is supposed to promote adhesion, migration and invasion. In cancer tissue, high levels of uPAR are correlated with a poor prognosis. This immunohistochemical study shows the localization of uPA and uPAR in a prospective design with stereological sampling of fetal and maternal tissue from normal, ectopic and hydatidiform molar (HM) pregnancies. Cytokeratin and Ki67 were used as markers for trophoblasts and proliferating cells. Membrane-bound uPAR was observed on villous non-proliferating intermediate trophoblasts (IT) within cell columns in intrauterine and ectopic pregnancies. The corresponding proliferating IT with cytological atypia sprouting from the chorionic villi in HM was uPAR-negative. uPA but not uPAR was observed in anchoring distal IT at the attachment-point to the basal plate. In the placental bed, extravillous interstitial trophoblasts were uPA-positive but uPAR-negative. The trophoblast giant cells were both uPA- and uPAR-negative. In relation to the maternal vessels, a focal distribution for uPA and uPAR was present in the endovascular and perivascular trophoblasts. The intraluminal trophoblasts overlying endothelial cells were uPAR-positive only. In maternal tissue from intrauterine and molar pregnancies, uPAR was seen in the decidual cells in a zone facing the anchoring villi and the fibrinoid lesions with embedded trophoblasts. In contrast, the stromal cells of the fallopian tube without a decidual reaction facing the implanted gestation were uPAR-negative. Non-invaded decidual, myometrial and muscular tissue of the pregnant uterus and fallopian tube was extensively positive for uPA whereas 'pseudodecidual' cells from the intrauterine evacuate in patients with an ectopic pregnancy only showed a focal and scanty reaction for uPA. When trophoblast invasion of the decidua was present, the decidual cells were uPA-negative. A semi-quantitative assessment of the receptor was estimated in villous IT within cell columns in normal and molar pregnancies but, in conclusion, quantitative evaluation of uPAR cannot be used to predict development of post-molar persistent trophoblastic disease (PTD).

Chorionic Villi Sampling↗
PubMed1999

Biological monitoring of sterilizers and sterilization failures in Norwegian dental offices in 1985 and 1996.

It is essential that dental office sterilizers be regularly challenged with biological indicators (BIs) in order to prove that the test spores are being killed during sterilization. The aims of the study were to biologically monitor Norwegian dental office sterilizers and to identify factors contributing to sterilization failure. In 1985, participants received a packet containing: (i) 4 BI units; (ii) a set of instructions; (iii) a questionnaire concerning operation (including biological monitoring) of the office sterilizer(s), and (iv) a return-address envelope. In 1996, offices were sent (i) a survey which included demographic questions and inquiries concerning instrument sterilization processes; (ii) 2 sets of 3 BI units with instructions for their use on 2 different days; (iii) 1 control BI unit that was not to be processed, and (iv) a return-address envelope. Both private and public offices participated. Response rate to the 1996 study was 60%, which was 9.1% of all dental offices in Norway. Testing results indicated a 6.3% overall sterilization failure rate. Three out of 163 steam autoclaves (SAs) (1.8% of total) and 14 out of 109 dry heat (DH) ovens (12.8% of total) failed. DH ovens were over 7 times more likely to fail BI testing than were SAs (chi2, P < 0.01). Demographic or hygiene procedural factors could not be correlated to sterilization performance (chi2, P > 0.05). The failure rate for SAs (n = 216) in 1985 was almost 5 times greater than in 1996 (8.8% vs 1.8%). Improvement in sterilizer performance during the decade may be related to issuance in 1986 of Norway's 1st infection control guidelines for dentistry and greater awareness of infection control practices and/or to increases over the previous 10 years in the number of postgraduate courses offered in infection control. The current Norwegian guidelines on infection control practices in public health services, including dentistry, recommend regular biological monitoring of sterilizers without specifying how often. There is a lack of information among Norwegian dentists as to how frequently dental office sterilizers should be regularly monitored by BI.

Chi-Square Distribution↗
PubMed1999

Oncoprotein MDM2 overexpression is associated with poor prognosis in distinct non-Hodgkin's lymphoma entities.

MDM2 is an oncoprotein involved in the regulation of p53. MDM2 exerts its tumorigenic potential through p53-dependent and -independent mechanisms. It is frequently overexpressed in various malignancies. Little is known about the prognostic value of MDM2 expression in non-Hodgkin's lymphomas (NHL). We analyzed MDM2 expression immunohistochemically in 188 NHL cases from a prospective population-based NHL registry. The aim was to identify MDM2 expression profiles in various histological NHL subtypes and analyze whether MDM2 expression correlated with clinical variables and p53 status. MDM2 overexpression was present in 42 (22%) of 188 cases. The frequency was highest in aggressive/very aggressive NHL (P < .0001). Furthermore, within follicle center lymphomas, MDM2 overexpression was associated with higher-grade disease (P = .008). MDM2 overexpression was not related to a phenotype indicating altered p53. In univariate analysis MDM2 overexpression associated with short survival in follicle center lymphomas (P = .0256), extranodal marginal zone lymphomas (P < .0001), and mantle cell lymphomas (P = .0047). The relation to poor prognosis was maintained in a Cox regression analysis including known prognostic factors (relative risk 5.5, P = .0022). The results of the present study suggest that MDM2 may play a role in lymphomagenesis and lymphoma progression through p53-independent mechanisms, and that MDM2 overexpression identifies a small fraction of follicle center lymphomas, extranodal marginal zone lymphomas, and mantle cell lymphomas with poor prognosis.

Female↗
PubMed1998

FH3, a domain found in formins, targets the fission yeast formin Fus1 to the projection tip during conjugation.

Formins are involved in diverse aspects of morphogenesis, and share two regions of homology: FH1 and FH2. We describe a new formin homology region, FH3. FH3 is an amino-terminal domain that differs from the Rho binding site identified in Bni1p and p140mDia. The Schizosaccharomyces pombe formin Fus1 is required for conjugation, and is localized to the projection tip in cells of mating pairs. We replaced genomic fus1+ with green fluorescent protein (GFP)- tagged versions that lacked either the FH1, FH2, or FH3 domain. Deletion of any FH domain essentially abolished mating. FH3, but neither FH1 nor FH2, was required for Fus1 localization. An FH3 domain-GFP fusion protein localized to the projection tips of mating pairs. Thus, the FH3 domain alone can direct protein localization. The FH3 domains of both Fus1 and the S. pombe cytokinesis formin Cdc12 were able to localize GFP to the spindle pole body in half of the late G2 cells in a vegetatively growing population. Expression of both FH3-GFP fusions also affected cytokinesis. Overexpression of the spindle pole body component Sad1 altered the distribution of both Sad1 and the FH3-GFP domain. Together these data suggest that proteins at multiple sites can interact with FH3 domains.

Actins↗
PubMed1998

A comparison of flow cytometry and immunohistochemistry in human colorectal cancers.

In human colorectal cancer it has been reported that some tumours lack the HLA-ABC antigens. This has been interpreted as reflecting tumour escape from the immune system. Earlier data have been obtained by immunohistochemistry. In this study, we compared the expression of HLA-ABC, HLA-DR, CD80 (B7-1) and CD54 (ICAM-1) in 20 tumours using both a conventional immunohistochemistry two-layer technique and multiparameter flow cytometry, gating on an epithelial cell marker. Colorectal cancer tissue used in flow cytometry was dissociated with collagenase, deoxyribonuclease and hyaluronidase. The intensity of expression of HLA-ABC, HLA-DR and CD80 was unaffected by the enzymes, but CD54 was decreased by 30%. The reproducibility of flow cytometry was good. Microscopy of sections revealed that about 5% of each tumour sample consisted of normal epithelium, but even after correction for this, flow cytometry was superior to immunohistochemistry in 33 out of 80 cases, and showed that tumours described as HLA-ABC negative by immunohistochemistry were in fact weakly positive for HLA-ABC. We conclude that flow cytometry and immunohistochemistry are complementary, and that flow cytometry is superior to immunohistochemistry for detecting antigens/epitopes present in low amounts.

Aged↗
PubMed1998

F-actin distribution and function during sexual differentiation in Schizosaccharomyces pombe.

Sexual differentiation in Schizosaccharomyces pombe is induced from the G1 phase of the cell cycle by nitrogen starvation and the presence of mating pheromones. We describe the distribution of F-actin during sexual differentiation. Cortical F-actin dots have previously been shown to be restricted to one end of the rod shaped cell during the G1 phase of the cell cycle. Within half an hour of nitrogen starvation the distribution of cortical F-actin dots switched from being monopolar to bipolar. This was then reversed as the F-actin cytoskeleton repolarized so that cortical F-actin dots accumulated towards the projection tip at one end of the cell. Following cell fusion, F-actin dots were randomly scattered during the horsetail movement that precedes meiosis I and remained scattered until prometaphase or metaphase of meiosis II, when they concentrated around the nucleus. F-actin was seen on the lagging face of the nuclei which faced the partner nucleus during anaphase B of meiosis II. Early on in this anaphase F-actin was also seen on the opposite side of the nucleus, near the spindle pole body. F-actin accumulated within the spores in the mature ascus. Treatment with the actin depolymerising drug Latrunculin A showed that F-actin is required for cell fusion and spore formation. Latrunculin A treatment extended all stages from karyogamy to meiosis I. The S. pombe homologue of the actin binding protein profilin, Cdc3, was shown to be required for conjugation. Cdc3 co-localized with the formin related molecule Fus1 at the projection tip. The polarization of F-actin cortical dots to the projection tip was unaffected in the cdc3.124 mutant, but cdc3.124 mutant cells were unable to break down the cell walls between the two cells following agglutination.

Actin Cytoskeleton↗
PubMed1997

Cell differentiation by interaction of two HMG-box proteins: Mat1-Mc activates M cell-specific genes in S.pombe by recruiting the ubiquitous transcription factor Ste11 to weak binding sites.

The Schizosaccharomyces pombe mfm1 gene is expressed in an M cell-specific fashion. This regulation requires two HMG-box proteins: the ubiquitous Ste11 transcription factor and the M cell-controlling protein Mat1-Mc. Here we report that the mfm1 promoter contains a single, weak Stell-binding site (a so-called TR-box) that can confer M-specificity on a heterologous promoter when present in eight copies. In vitro, both Mat1-Mc and Ste11 can bind this box with approximately the same affinity. The Mat1-Mc protein caused a dramatic increase in the DNA-binding of Ste11 to this box, under conditions where we could not detect Mat1-Mc in the resulting protein-DNA complex. When we changed a single base in the mfm1 TR-box, such that it resembled those boxes found in ubiquitously expressed genes, Ste11 binding was enhanced, and in vivo the mfm1 gene also became expressed in P cells where Mat1-Mc is absent. These findings suggest that M-specificity results from Mat1-Mc-mediated Ste11 binding to weak TR-boxes. We have also defined a novel motif (termed M-box), adjacent to the mfm1 TR-box, to which Mat1-Mc binds strongly. A DNA fragment containing both the TR- and the M-box allowed the formation of a complex containing both Ste11 and Mat1-Mc. A single copy of this fragment was sufficient to activate a heterologous promoter in an M-specific fashion, suggesting that these two boxes act in a synergistic manner.

Base Sequence↗
PubMed1997

Abc1: a new ABC transporter from the fission yeast Schizosaccharomyces pombe.

We have isolated the abc1 gene from the fission yeast Schizosaccharomyces pombe. Sequence analysis suggests that the Abc1 protein is a member of the ABC superfamily of transporters and is composed of two structurally homologous halves, each consisting of a hydrophobic region of six transmembrane domains and a hydrophilic region containing one ATP-binding site. The abc1 gene appears to be expressed under all growth conditions but gene disruption experiments indicate that it is not essential for growth. The sequence of the abc1 gene has been deposited in the EMBL data library under the Accession Number Y09354.

ATP-Binding Cassette Transporters↗
PubMed1997

The Schizosaccharomyces pombe mam1 gene encodes an ABC transporter mediating secretion of M-factor.

In the fission yeast Schizosaccharomyces pombe, cells of opposite mating type communicate via diffusible peptide pheromones prior to mating. We have cloned the S. pombe mam1 gene, which encodes a 1336-amino acid protein belonging to the ATP-binding cassette (ABC) superfamily. The mam1 gene is only expressed in M cells and the gene product is responsible for the secretion of the mating pheromone. M-factor, a nonapeptide that is S-farnesylated and carboxy-methylated on its C-terminal cysteine residue. The predicted Mam1 protein is highly homologous to mammalian multiple drug-resistance proteins and to the Saccharomyces cerevisiae STE6 gene product, which mediates export of a-factor mating pheromone. We show that STE6 can also mediate secretion of M-factor in S. pombe.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Epizootiology of morbillivirus infection in harp, hooded, and ringed seals from the Canadian Arctic and western Atlantic.

Using a virus neutralization technique, we found phocine distemper virus (PDV) antibody in 130 (83% of 157) harp seals (Phoca groenlandica) from the western North Atlantic sampled between 1988 and 1993 inclusive. In contrast, only 44 (24% of 185) hooded seals (Cystophora cristata) had antibodies against PDV even though they were sympatric with harp seals and were sampled over a similar period, from 1989 to 1994 inclusive. Antibodies occurred in 106 (41%) of 259 ringed seals (Phoca hispida); this prevalence was higher than expected given the solitary behavior and territoriality characteristic of this species. Seropositive ringed seals were found at each of seven locations across Arctic Canada from Baffin Bay to Amundsen Gulf at which samples were collected between 1992 and 1994. However, the prevalence of infection was highest where ringed seals are sympatric with harp seals in the eastern Canadian Arctic.

Animals↗
PubMed1997

Ecosystem health as a clinical rotation for senior students in Canadian veterinary schools.

We describe 4 years of an experimental rotation in ecosystem health offered to senior veterinary students in Canada. Faculty from the 4 Canadian veterinary colleges collaborated in offering the rotation once annually at 1 of the colleges. The 1st rotation was held in Guelph in 1993, followed in successive years by rotations at Saskatoon, Saint-Hyacinthe, and Charlottetown. The rotation is a predominantly field-based experience that allows students to work with veterinary and other role models who are actively engaged in clinical research related to ecosystem health. Five specific field studies that worked particularly well during the rotations are presented. These studies involved investigating mortality in wildlife due to botulism, designing an environmental surveillance system around herds of beef cattle, using belugas to evaluate the health of the St. Lawrence River, dealing with competition for water use by aquaculture and agriculture, and exploring the role of veterinarians during major coastal oil spills. The experience has resulted in our developing the subject matter, field examples, teaching approach, and confidence necessary to make ecosystem health the focus of a productive clinical rotation for senior year veterinary students.

Agriculture↗
PubMed1996

The Schizosaccharomyces pombe map1 gene encodes an SRF/MCM1-related protein required for P-cell specific gene expression.

Cells of Schizosaccharomyces pombe undergo mating and meiosis when starved for a nitrogen source. In this process a P and and M cell first mate to generate a diploid zygote, which subsequently enters meiosis and sporulates. The P mating type is controlled by the mat1-Pc gene at the mating type locus, together with a gene called map1. We show that these two functions are required for expression of the P-specific gene map3. We have cloned the map1 gene and show that it encodes a putative MADS-box containing transcription factor related to mammalian Serum Response Factor (SRF) and Saccharomyces cerevisiae MCM1. The Mat1-Pc protein contains a motif characteristic for proteins that interact with MADS-box factors, suggesting that Mat-Pc and Map1 may form a heterodimer that activates the P-specific map3 gene.

Amino Acid Sequence↗
PubMed1996

Structural requirements for alpha-mating factor activity.

The sexual hormone of S. cerevisiae, alpha-mating factor (alpha-MF, WHWLQLKPGQPMY) has structural homology with mammalian luteinizing hormone releasing hormone (LHRH, pEHWSYGLRPG-NH2) and has been shown to exhibit LHRH activity [Loumaye et al. (1982) Science 218, 1323-1325]. We have tested whether LHRH has alpha-MF activity in yeast and found that it does not. We therefore synthesized a series of hybrid peptides of alpha-MF and LHRH to study the structural features which determine alpha-MF and LHRH activities. A hybrid peptide consisting of the LHRH sequence with the C-terminal tetrapeptide (QPMY) of alpha-MF did not exhibit alpha-MF activity. Thus, the lack of alpha-MF activity of LHRH is not due solely to the absence of the C-terminal residues. Substitution of Lys7 in alpha-MF with Arg, as is found in LHRH, did not affect the alpha-MF activity, nor did an additional substitution of Trp1 with pGlu. However, the C-terminal four amino acids of alpha-MF were necessary for alpha-MF activity. Our results indicate that insertion of a Ser residue in position 4 as found in LHRH abolishes alpha-MF activity. These results suggest that, in addition to an intact C-terminus, correct spacing of the N-terminal His2 and the C-terminus is required for alpha-MF activity. The hybrid peptides all exhibited less LHRH activity than either LHRH or alpha-MF. These structure-function studies indicate that the structural homology between these two reproductive hormones may not reflect an evolutionary relationship between them.

Amino Acid Sequence↗