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Biomedical subjects

P Ebbesen

Publications and source records attributed to P Ebbesen.

At least 91 records · Page 5Linked to original sources

Markers for human placental trophoblasts in two-dimensional gel electrophoresis.

Primary cultures of trophoblasts established from human term placentae showed high viability and reproducibility. Two-dimensional gel patterns obtained by metabolically labeling the trophoblasts with [35S]-methionine demonstrated that their pattern of gene expression was stable during the 6-d period investigated. Gel analysis demonstrated the keratins 7, 8, 14, 17, 18, and 19. Analysis of the gel pattern confirmed the presence of a small proportion of contaminating fibroblasts and lymphocytes. The gel patterns were compared with that of skin fibroblasts, peripheral lymphocytes, and epithelial cells to identify a group of proteins that are enriched in the trophoblasts and thus may be used as marker for these cells.

Cells, Cultured↗

Interferon production by cultured human trophoblast induced with double stranded polyribonucleotide.

Human trophoblast cultures were established from term placentae. Upon exposure to polyriboinosinic-polyribocytidylic acid (poly(I:C] the cultures produced interferon. Results of neutralization experiments and indirect immunofluorescence studies indicated that the trophoblast produces beta-interferon. The fusion of trophoblast cells into syncytia was accompanied by a restriction in interferon release after stimulation with poly(I:C). It was also demonstrated that the malignant choriocarcinoma cell line JAR produced less interferon than the non-transformed cytoorsyncytiotrophoblast.

Cell Separation↗

Lysosomal degradation of receptor-bound urokinase-type plasminogen activator is enhanced by its inhibitors in human trophoblastic choriocarcinoma cells.

We have studied the effect of plasminogen activator inhibitors PAI-1 and PAI-2 on the binding of urokinase-type plasminogen activator (u-PA) to its receptor in the human choriocarcinoma cell line JAR. With 125I-labeled ligands in whole-cell binding assays, both uncomplexed u-PA and u-PA-inhibitor complexes bound to the receptor with a Kd of approximately 100 pM at 4 degrees C. Transferring the cells to 37 degrees C led to degradation to amino acids of up to 50% of the cell-bound u-PA-inhibitor complexes, whereas the degradation of uncomplexed u-PA was 15%; the remaining ligand was recovered in an apparently intact form in the medium or was still cell associated. The degradation could be inhibited by inhibitors of vesicle transport and lysosomal hydrolases. By electron microscopic autoradiography, both 125I-u-PA and 125I-u-PA-inhibitor complexes were located over the cell membrane at 4 degrees C, with the highest density of grains over the membrane at cell-cell interphases, but, after incubation at 37 degrees C, 17 and 27% of the grains for u-PA and u-PA-PAI-1 complexes, respectively, appeared over lysosomal-like bodies. These findings suggest that the u-PA receptor possesses a clearance function for the removal of u-PA after its complex formation with a specific inhibitor. The data suggest a novel mechanism by which receptor-mediated endocytosis is initiated by the binding of a secondary ligand.

Cell Line, Transformed↗

Purification and initial characterization of human placental trophoblast interferon induced by polyriboinosinic.polyribocytidylic acid.

Human placental trophoblast interferon (tro-IFN), induced in trophoblast cultures by a superinduction procedure, was purified to a homogeneous product with retention of biological activity. The problems associated with isolation from serum-containing medium were overcome by a combination of Blue Sepharose affinity chromatography and reversed-phase HPLC (RP-HPLC) on Separon SGX C-18. This two-step purification procedure yielded tro-IFN with a specific activity of 3.4 x 10(7) international units/mg of protein. The overall recovery of interferon activity was 66.7%. The purified tro-IFN was shown to be a glycoprotein with an Mr of 24K on native and SDS-PAGE. Its antiviral activity was stable at pH 2.0 at 37 degrees C but was sensitive to heat at 56 degrees C for 1 h and was neutralized by antibodies to human IFN-beta.

Cell Line↗

Interferon production by cultured human trophoblasts and choriocarcinoma cell lines induced by Sendai virus.

Human term-placental trophoblasts in primary culture were studied for an interferon (IFN) response when challenged with Sendai virus and compared to three choriocarcinoma cell lines, placental fibroblasts and placental macrophages. Normal trophoblasts were high producers and released both IFN-alpha and IFN-beta. In contrast, one choriocarcinoma cell line was a low producer and all malignant lines produced only IFN-beta. Circulating monocytes produce IFN-alpha but placental macrophages secreted IFN-beta and some IFN-alpha, suggesting that IFN production may be dependent on the stage of differentiation. A role for trophoblast IFNs in protection of the foetus against virus infections is proposed.

Antibodies↗

Bleomycin-iron complexes and DNA radiation damage.

Radiation in the form of high-energy electrons dose-dependently activates bleomycin-Fe3+ in oxygen-containing DNA solutions. This activation causes a DNA fragmentation and a release of oxidative degradation products from the DNA. During irradiation, bleomycin-chelated Fe3+ is reduced to Fe2+. The kinetics of DNA base propenal-formation (measured by reaction with thiobarbituric acid) and iron-reduction (measured by bathophenanthroline chelation) are similar, with a yield of 1 mol base propenal/6 mol Fe3+ reduced. The activation of bleomycin-Fe3+ by irradiation could be instrumental in the synergistic action of radiotherapy and bleomycin observed on simultaneous administration in vivo.

Bleomycin↗

Effect of knowledge of human immunodeficiency virus infection status on sexual activity among homosexual men.

One hundred thirty-four homosexual men from a prospective cohort study of AIDS risk from New York City and Washington D.C. and 139 homosexual men from a similar cohort in Copenhagen and Aarhus, Denmark were questioned regarding their sexual practices and knowledge of their human immunodeficiency virus (HIV) status over the previous 12 months. Seventy percent of Danish men and 63% of U.S. men participated in anal intercourse during the previous 12 months. Knowledge of one's own HIV status by itself did not have any significant effect on participation in anal intercourse, partner number, or condom use. Only 23% of U.S. men and 24% of Danish men always asked potential partners about their HIV status. However, men who did ask were very unlikely to choose a partner of opposite HIV status (p less than 0.006). Danish men were more likely to practice anal intercourse without a condom than were the U.S. men (p less than 0.0001); however, Danes were more likely to be in a concordant monogamous relationship than were the U.S. men (p less than 0.001). Fourteen percent of U.S. men and 21% of Danish men were not aware of their own HIV status and 52% of the U.S. cohort and 31% of the Danes had anal intercourse with a man whose status was unknown to them. Overall, only 32% of American and 53% of Danish homosexual men were practicing completely safe sex. We suggest that education to promote the need for awareness of one's own and one's partner's HIV status should be stressed.

Acquired Immunodeficiency Syndrome↗

Explants of human oral epithelium exposed to viruses and cancer chemotherapeutics.

Cultures of proliferating epithelial cells were established from explants of normal human oral epithelium from healthy young volunteers. The epithelial cells were found permissive for herpes simplex virus type 1 and type 2, coxsackie virus A-4 and A-16, adenovirus type 5, measles vaccine, rubella and influenza type A virus-. Medium from DEAE-pretreated epithelial cultures infected with two subtypes of human immunodeficiency virus-1 showed an increasing content of virusprotein with time by antigen ELISA testing. In contrast there was no evidence of infection with coxsackie virus type B-2, cytomegalovirus, Epstein-Barr virus and varicella zoster virus. Treatment of the epithelial cells with a non-cytotoxic dose of cancer chemotherapeutic prior to or after infection with coxsackie virus A-4 or herpes simplex virus type 1 influenced the virus production dependent on both compound, mode of application, and virus. Adriamycin (doxorubicin) in low dose was found to stimulate the production of the two viruses.

Adult↗

Diffusion of HIV-1 virus into non-habitual categories at risk in European countries.

The ECP Working Group on AIDS has evaluated the available data on seropositivity to HIV-1 supplied by research groups in 12 Eastern and Western European countries. The period covered is 1985 and 1986. A significantly elevated incidence of seropositives was observed in both females and males in heterosexual contact with members of high risk groups. In contrast heterosexuals with no such contact had an incidence below 1%. For male homosexuals from Italy, Denmark and Switzerland the trend was no detectable increase in prevalence from 1985 to 1986. Hungary and Poland now have a few per cent seropositive male homosexuals, but no seropositives were found in a group of Polish drug abusers.

Bisexuality↗

Hepatitis B virus infection in Danish dentists. A case-control and follow-up study.

The authors determined the seroprevalence of hepatitis B virus markers among Danish dentists in 1985 in an effort to assess occupational risk factors. A case-control study approach was applied using pedodontists as zero-exposure controls. The study further allowed serologic and epidemiologic follow-up of dentists who participated in a similar study in 1976. The authors sought to determine whether exposure to hepatitis B virus in this population sometimes leads to immunization without infection (antibody to hepatitis B surface antigen (anti-HBs) positivity only). A total of 922 dentists (22% of all Danish dentists) gave blood; of these, 254 (28%) participated in the 1976 study. Serum samples were tested using commercial solid phase radioimmunoassays. The prevalences of anti-HBs and antibody to hepatitis B core antigen (anti-HBc) were 7.2% (95% confidence interval (CI) = 5.7-9.0) and 5.2% (95% CI = 3.8-6.6), respectively. Twenty-one dentists (31%) only had anti-HBs (without prior vaccination). Age-standardization of the two data sets (1976 and 1985) indicated no substantial change in seroprevalence. Private practitioners, especially those working in Copenhagen, had an increased odds ratio (OR) of being seropositive compared with that of pedodontists (OR = 3.0 (95% CI = 1.3-6.8) adjusted for age and sex and OR = 2.4 (95% CI = 1.1-5.2) adjusted for age and site of practice). The proportion attributable to occupational exposure was approximately 50%. In a logistic regression model, site of practice and type of specialty were associated with hepatitis B virus seropositivity (p = 0.01 and 0.05, respectively), whereas age, sex, hours of oral surgery per week, and use of gloves were not. Four persons had become seropositive in the follow-up study, for a seroconversion rate of 0.2% per year. Seven out of 18 dentists who were anti-HBs positive in 1976 were found to be anti-HBs negative in 1985. Most of these dentists had values below 10.0 units by S/N ratio (ratio of counts per minute of sample compared with the mean number of counts per minute of negative controls). The findings do not justify institution of a large-scale vaccination program for dentists, but there are certain subgroups of dentists which constitute candidates for vaccination.

Adult↗

Antibody to human papilloma virus in Danish dentists.

The aim of this study was to investigate the seroprevalence of antibody to human papilloma virus (HPV) among Danish dentists in order to determine whether this virus constitutes an occupational hazard for dentists. Serum samples from 452 Danish dentists were tested for antibody against a common capsid antigen to HPV by a complement fixation reaction. Nine (2.0%) were seropositive. Dentists' odds ratio for seropositivity was after adjustment for age 0.6 (90% confidence interval: 0.3-1.4) compared to that of voluntary blood donors. In conclusion, Danish dentists do not seem to be at an increased risk of becoming infected with HPV.

Antibodies, Viral↗

A suction blister method that gives epidermal biopsies from mice of different ages, suitable for histologic studies of Langerhans cells.

A modified suction blister device has been developed. It allows in vivo retrieval of 3 x 3 mm2 mouse epidermis biopsies. Separation takes place exactly at the epidermal-dermal junction. Young skin and iso-grafted skin require suction with a lower bar value than skin from young and old non-grafted animals. Langerhans cells in biopsies were identified both with ATPase staining and with monoclonal antibody. Suction blisters produce Langerhans cell counts similar to those obtained on EDTA-separated epidermis.

Aging↗

Syngrafting skin among mice of similar and different ages increases the number of Langerhans cells and decreases responsiveness to 1,4-dinitrofluorobenzene.

Counting on suction blister skin biopsies, the number of Langerhans cells per mm2 in BALB/c mouse epidermis was found identical in 1-, 11-, and 22-month-old animals, but consistently elevated in syngrafted skin 10 months after transplantation. This effect of grafting was independent of whether young or old skin was transferred to young or old recipients. Skin swelling induced by dinitrofluorobenzene (DNFB) sensitization was reduced in 22-month-old non-grafted mice and in grafted skin irrespective of donor and recipient age.

Aging↗

Relevance of aging research for cancer.

Experimental studies of the survival curves of different species and of in vitro cell culture survival point to normal aging as a largely preprogrammed process. Reciprocal skin grafting among syngeneic young and old animals further demonstrates autonomous aging of this organ independent of the remainder of the body. This compartmentalization of change with age is also suggested when immune functions of various lymphoid organs are compared at different ages. Experimental studies also show that for some organs their susceptibility to certain carcinogens is diphasic, high early in life and high in senescence. A major question now is if preprogrammed age changes at the molecular level have steps in common with carcinogenetic processes.

Aging↗

Seropositivity to LAV/HTLV-III in 11 European countries.

The ECP Working Group on AIDS has evaluated data on seropositivity to LAV/HTLV-III supplied by members in II Western European countries. The period covered is 1981-84. The rise in LAV/HTLV seropositivity parallels the incidence of cases of AIDS in the different countries. LAV/HTLV now spreads freely within Europe and spread has become less dependent upon promiscuity. The epidemic is about to enter Eastern Europe. Intravenous drug abusers appear to be the risk group experiencing the most rapid spread at present. Furthermore, seropositivity in males and females outside the traditional risk groups seems on the rise, and as in the US the percentage seronegative in individuals with PGL is quite high. AIDS is rapidly becoming a major cause of cancer in young adults. A coordinated European preventive effort is urgently needed.

Acquired Immunodeficiency Syndrome↗