PubMed Health⌕ Search

Biomedical subjects

C M Petersen

Publications and source records attributed to C M Petersen.

At least 55 records · Page 3Linked to original sources
PubMed1990

Pregnancy zone protein: a re-evaluation of serum levels in healthy women and in women suffering from breast cancer or trophoblastic disease.

Pregnancy zone protein (PZP) and alpha 2-macroglobulin (alpha 2M) serum concentrations were studied in healthy female donors, in women suffering from benign and malignant breast tumours, and in relation to normal and abnormal pregnancies. PZP was found to be useless as a tumour marker. Thus, PZP levels in breast cancer patients did not differ from those of fibroadenoma patients or healthy women. There was no correlation between PZP (or alpha 2M) concentrations and the pTNM-classification or metastatic burden of the breast cancer patients. Moreover, PZP levels were unaffected by cancer treatment and the course of disease. Neither patients nor control donors showed any age-dependent increase in circulating PZP and the mean serum value (8.38 +/- 4.83 mg/l, mean +/- SD) determined in a population of 154 non-pregnant women was considerably lower than that of most previous reports. Serum concentrations were unchanged during the normal menstrual cycle, but increased during pregnancy. However, late pregnancy sera (35th gestational week) contained significantly less PZP than previously reported by others, and non-pregnancy levels were observed in one out of 22 cases. Results obtained in hydatidiform mole patients were similar to findings in normal pregnancy. Neither serum 17 beta-oestradiol nor morphological differentiation between complete and partial mole showed any correlation with circulting PZP levels. Apart from a moderate increase during gestation, alpha 2M concentrations showed little variation between the populations examined.

Adult↗
PubMed1989

Immunosuppressive properties of electrophoretically "slow" and "fast" form alpha 2-macroglobulin. Effects on cell-mediated cytotoxicity and (allo-) antigen-induced T cell proliferation.

Lymphokine activated killer cell lysis of K562 cells was inhibited by alpha 2-macroglobulin (alpha 2M), soybean trypsin inhibitor, and alpha 1-proteinase inhibitor. In serum free medium 2 mg/ml alpha 2M suppressed target cell lysis in a 4-h cytotoxic assay with about 40%. Suppression was dose and time dependent. Cytotoxicity was unaffected by alpha 2M concentrations less than 0.25 mg/ml, and by alpha 2M added later than 1.5 h from start of assay. Pre-treatment of effector (but not of target) cells with alpha 2M was even more suppressive than the presence of alpha 2M during assay. Cell-mediated cytotoxicity was not inhibited by alpha 2M treated with methylamine or by various alpha 2M-proteinase complexes. In contrast, alpha 2M-proteinase complex as well as native alpha 2M suppressed the proliferation of Ag-activated T cells. However, methylamine-treated alpha 2M did not inhibit T cell proliferation, and suppression by alpha 2M-proteinase complex was significantly reduced after inhibition of the alpha 2M-bound proteinase. On incubation at 4 degrees C with lymphokine-activated killer cells, alpha 2M reacted with cell associated proteinases and changed from electrophoretically "slow" to "fast" form. Cell associated proteinases bound by alpha 2M showed chymotrypsin- and trypsin-like specificities and their activity surpassed activity caused by cellular leakage and secretion. The present results strongly indicate that alpha 2M mediates immunosuppression in its capacity as a proteinase inhibitor and suggest inhibition of (T)cell surface-associated proteinases as a possible mode of suppression.

Cytotoxicity Tests, Immunologic↗
PubMed1989

Bioactive human recombinant tumor necrosis factor-alpha: an unstable dimer?

As determined by native polyacrylamide gel electrophoresis (PAGE) and gel chromatography the molecular mass of native tumor necrosis factor (TNF)-alpha was approximately 35 kDa. When incubated at low concentrations (less than 1 nM) 125I-labeled TNF-alpha and unlabeled TNF-alpha rapidly multimerized or dissociated into monomers and bioactivity decreased. Sodium dodecyl sulfate (SDS)-PAGE analysis of cross-linked 125I-labeled TNF-alpha demonstrated bands of multi- and trimeric TNF-alpha in addition to dominating bands of dimers and monomers. Tri-, di- and monomeric TNF-alpha were recovered from SDS-PAGE gels and allowed to renature. Of the original receptor-binding activity, 10%-15% was obtained with cross-linked TNF-alpha dimers, whereas none was recovered from preparations of trimeric TNF-alpha. Multimeric and monomeric TNF-alpha exhibited little or no binding activity, and cell-bound, cross-linked TNF-alpha which was dissociated from cellular binding sites was mainly dimeric. 125I-labeled TNF-alpha bound to lymphokine-activated killer (LAK) cells and binding kinetics were much similar (Kd approximately 100 pM) to those reported in other normal cell types. The number of receptors per LAK cell was approximately 4 x 10(3). Cross-linking of TNF-alpha to binding sites in U-937 and LAK cells yielded a receptor-ligand complex of about 80/90 kDa. At 37 degrees C, 125I-labeled TNF-alpha was rapidly internalized and degraded in L-929, U-937 and LAK cells. Degradation of ligand and recycling of receptors were blocked in the presence of methylamine. Methylamine significantly inhibited TNF-alpha-mediated cytolysis of L-929 cells and caused a quantitatively corresponding reduction in cellular TNF-alpha uptake, indicating that L-929 lysis was mediated by receptors.

Cell Survival↗
PubMed1989

Effects of 3'-azido-3'-deoxythymidine (AZT) on short-term cultured human peripheral blood lymphocytes.

Although an optimal dose-regimen has still not been established, the antiviral drug 3'-azido-3'-deoxythymidine is known to improve the clinical condition of patients suffering from acquired immunodeficiency syndrome and acquired immunodeficiency syndrome-related complex. The drug effect has mainly been assessed in terms of survival time and/or immunological parameters. One of the most prominent immunological features associated with immunodeficiency virus infection is a persistant hypergammaglobulinaemia due to in vivo polyclonal B-lymphocyte activation. In vitro this is reflected by a hyporesponsiveness of peripheral blood B-lymphocytes to mitogen and antigen induced activation. The present paper deals with the in vitro impact of 3'-azido-3'-deoxythymidine on the immunoglobulin secretion in short-term cultures of peripheral blood lymphocytes. Twenty-four human immunodeficiency virus antibody positive (seropositive) and 24 antibody negative (seronegative) individuals were studied. In addition, T- and B-cell proliferation and the distribution of cell surface markers were determined in 3'-azido-3'-deoxythymidine-supplemented cultures of peripheral blood lymphocytes from eight seronegative subjects. At concentrations similar to those reported in clinical trials, 3'-azido-3'-deoxythymidine was found to suppress the mitogen and antigen induced proliferation of T-cells from seronegative subjects. In contrast, B-cell proliferation and the distribution of membrane markers appeared to be unaffected by the drug. Furthermore, 3'-azido-3'-deoxythymidine did not alter the in vivo immunoglobulin secretion capacity in autologous or allogeneic cultures of lymphocytes from seropositive subjects. In human immunodeficiency virus-infected individuals the number of unactivated, circulating B-cells is significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Cyclosporin A mediated immunosuppression in vitro: effect on high affinity interleukin-2 receptor expression and -turnover.

The effect of in vitro administration of Cyclosporin A (CsA) during mitogen, antigen and alloantigen activation of human T-lymphocytes on high affinity interleukin-2 (IL-2) receptor expression and -turnover and IL-2 production was investigated. The presence of CsA reduced 3H-thymidine incorporation and binding of radiolabelled human recombinant (ala125) IL-2 to high-affinity receptors in a dose-dependent fashion, although a pronounced inter- and intra-individual variation in sensitivity to CsA mediated immunosuppression was observed. Maximum inhibition was obtained when antigen and CsA were added to culture medium simultaneously. Preincubation with CsA did not influence the response. Although the number of IL-2 receptors was reduced, the turnover of the remaining high affinity IL-2 receptors on CsA treated cells was unaffected. Thus, binding, internalization and degradation were qualitatively unaltered by CsA administration. Finally, T cell activation in the presence of CsA reduced radioimmuno detectable IL-2 in cell culture supernatants to about 20%. CsA, added during antigen activation, reduced the number of Tac antigen presenting cells, but anti-Tac was unable to detect variations in the expression of high affinity IL-2 receptors. The present data indicate that CsA mediates immunosuppression by affecting early events during T-cell activation, and that variations in high affinity IL-2 receptor expression and IL-2 production are secondary to this affection.

Antigen-Presenting Cells↗
PubMed1988

Human hepatocytes exhibit receptors for alpha 2-macroglobulin and pregnancy zone protein-proteinase complexes.

Hepatocytes were isolated by application of the two-step collagenase technique to pieces of human liver. 125I-labelled alpha 2-macroglobulin-trypsin complex bound to hepatocytes at 4 degrees C with a half time of approximately 4.5 h. At near equilibrium half of the receptors were saturated at an alpha 2-macroglobulin-trypsin complex concentration of about 60 pmol 1(-1) and the Scatchard plot was linear. Dissociation of the labelled complex was slow (T1/2 = 24 h) at low receptor occupancies. At high receptor occupancies dissociation was biphasic with a rate constant (K-1) for the initial rapid phase of about 2.4 x 10(-2) min-1. Labelled alpha 2-macroglobulin-trypsin complex bound at 4 degrees C was rapidly internalized at 37 degrees C (T1/2 = 1.9 min), and in 3.5 h approximately 10% of the label was released into the medium in a trichloroacetic acid-soluble form. At 37 degrees C, 125I alpha 2-macroglobulin-trypsin was taken up by hepatocytes and trichloroacetic acid soluble radioactivity appeared in the medium following a sigmoidal curve. Similar results were obtained with 125I-pregnancy zone protein-chymotrypsin complex. At 4 degrees C, hepatocytes bound nearly equal amounts of labelled alpha 2-macroglobulin-trypsin and pregnancy zone protein-chymotrypsin complex, and a large excess (100 nmol 1(-1) of one of the macroglobulins could almost completely abolish binding of trace amounts (5-20 pmol 1(-1] of the other. The present findings strongly suggest that the hepatocyte is of major importance for removal of alpha 2-macroglobulin- and pregnancy zone protein-proteinase complex in humans, in agreement with previous results in rats and mice.

Biological Transport, Active↗
PubMed1988

Cell association and degradation of pregnancy zone protein-chymotrypsin complex in cultured human monocytes.

125I-labelled pregnancy zone protein complexed with chymotrypsin (PZP-ct) bound to freshly isolated and to cultured human monocytes. Binding of uncomplexed 125I-pregnancy zone protein (PZP) was less than 20% of complex binding. At 4 degrees C, labelled PZP-ct complex bound to cultured monocytes with a half-time of about 4 h. Dissociation at 4 degrees C was slow at low receptor occupancies (t 1/2 greater than 24 h). At high receptor occupancies, dissociation was biphasic (initial k-1 = 8 X 10(-3) min-1) and 85% of the cell-associated label had dissociated within 24 h. At near equilibrium, binding of 20 pmol/l 125I-PZP-ct was half maximally inhibited at a ligand concentration of about 450 pmol/l. The Scatchard plot was linear giving an estimated concentration of 2 X 10(4) receptors/cell. Ligand bound at 4 degrees C was rapidly internalized at 37 degrees C (half-time = 0.5 min) and after a 5-10 min lag time, radioactivity comprising monoiodotyrosine was released into the medium following a sigmoidal curve. At 37 degrees C the uptake of 125I-PZP-ct complex was initially linear and within 15 min internalized label accumulated, reaching a steady state at about 85% of the cell-associated radioactivity. Following a lag time of 15 min, radioactivity soluble in trichloroacetic acid appeared in the medium. Similar results were obtained with 125I-alpha 2-macroglobulin-trypsin complex (alpha 2M-T). It is concluded that high affinity receptors mediate binding, uptake and degradation of pregnancy zone protein--and alpha 2-macroglobulin-proteinase complex in human monocyte-macrophages.

Cells, Cultured↗
PubMed1988

Human hepatocytes in culture synthesize and secrete fibronectin.

Hepatocytes were isolated by application of the two-step collagenase perfusion technique to pieces of human liver. Hepatocytes were cultivated in serum-free medium or 10% fetal calf serum medium supplemented with insulin, glucagon and dexamethasone. The cells were kept in culture for up to 16 days and 75% of the medium was regularly changed. Fibronectin in culture medium was detected by means of an ELISA with an assay range of 2.2-560 micrograms/l. The interassay imprecision was 6.3% at 500 micrograms/l and 14.3% at 10 micrograms/l. Significant amounts of fibronectin were detected in all cultures. During culture, fibronectin accumulated in the medium and the quantity secreted by hepatocytes by far exceeded the amounts of fibronectin associated with hepatocytes prior to cultivation. Maximum secretion rate by 10(6) hepatocytes was 167.5 +/- 73.3 ng fibronectin (mean +/- SEM, n = 3) in 24 h. When analysed by means of SDS-PAGE and immunoblotting the fibronectin isolated from hepatocyte culture medium and cell lysate co-migrated with fibronectin obtained from plasma. Our data show, for the first time, that human hepatocytes synthesize and secrete fibronectin, and it is suggested that the human liver is an important source of plasma fibronectin.

Cells, Cultured↗
PubMed1987

Open study of 2-amino-9-(hydroxyethoxymethyl)-9H-purine (desciclovir) in the treatment of herpes zoster.

An oral pro-drug of acyclovir, 2-amino-9-(2-hydroxyethoxymethyl)-9H-purine (desciclovir) was evaluated in an open study comprising of 20 patients with herpes zoster. The clinical effects were comparable to those obtained with oral and intravenous acyclovir, even with a dosage of only 125 mg thrice daily. There was adequate absorption though considerable individual variation occurred. No effects of concomitant food intake were demonstrated. The finding of possible impaired conversion of desciclovir to acyclovir in one patient was unexplained and deserves attention in future studies. Likewise, more studies are needed to understand the occurrence of transient high peak plasma concentrations of acyclovir. Side-effects other than those already known with the use of acyclovir, namely reversible tubular damage, were not observed.

Acyclovir↗
PubMed1987

Comparison of the effectiveness of two pelvic stabilization systems on pelvic movement during maximal isometric trunk extension and flexion muscle contractions.

The purpose of this study was to compare the effectiveness of two pelvic fixation systems to limit pelvic movement during isometric trunk extension and flexion muscle strength testing. We developed a prototypal pelvic fixation system and compared it with a pelvic strap stabilization system. The prototypal pelvic fixation system consisted of fixation of the anterior superior iliac spines and sacrum, and the pelvic strap stabilization system consisted of a strap across the anterior superior iliac spines and a posterior pad. Small, but statistically significant, pelvic position changes occurred during isometric trunk extension and flexion muscle strength testing with the two stabilization systems. The pelvic angle changes were greater in extension than in flexion and greater when only the pelvic strap stabilization system rather than the prototypal pelvic fixation system was used. Our findings indicate that a more extensive prototypal pelvic fixation system minimizes pelvic movement to a greater extent during isometric trunk extension and flexion muscle contractions compared with the strap stabilization system.

Abdominal Muscles↗
PubMed1987

Cytotoxic human HLA class II restricted purified protein derivative-reactive T-lymphocyte clones. IV. Analysis of HLA restriction pattern and mycobacterial antigen specificity.

Human T-lymphocyte clones specific for antigenic components of purified protein derivative (PPD) of tuberculin were generated by limiting dilution using in vitro PPD-activated peripheral blood mononuclear cells from a single donor. The HLA restriction specificity of eight clones that were cytotoxic against autologous PPD-pulsed monocyte targets, was examined against a panel of allogeneic PPD pulsed targets. In agreement with our findings with bulk-expanded PPD-reactive cytotoxic T lymphocytes, all clones were restricted by HLA class II antigens: seven by HLA-DR 2 and one by HLA-DRw10--the other HLA-DR antigen of the donor. All clones were CD3+, CD4+, CD8-. One clone exhibited, in addition to HLA-DR2 restriction, unrestricted cytotoxic alloreactivity against HLA-DR1. In monoclonal antibody-blocking experiments the latter clone was the only one that was blocked. Its lytic ability was abolished by two monoclonal antibodies against monomorphic HLA-DR determinants. The antigen specificity of the clones was studied by using autologous monocyte targets pulsed with antigens prepared from a range of different mycobacterial species. All seven HLA-DR2-restricted clones reacted with the majority of antigens tested. In contrast, the HLA-DRw10-restricted clone reacted exclusively with an antigen unique to PPD.

Antibodies, Monoclonal↗
PubMed1987

Binding, uptake and degradation of human recombinant interleukin-2 (125 ala) in activated human T- and B-lymphocytes and in monocyte-macrophages.

High-affinity receptors for IL-2 (ala 125) were demonstrated in PHA-, antigen- and/or alloantigen-activated human T-cells (both proliferative and cytotoxic), in PWM-activated human B-cells and in human monocyte-macrophages. Binding in PHA-blasts was irreversible and Ca++-independent, and labelled IL-2 (ala 125) bound at 4 degrees C could not be removed by trypsin treatment. Binding was strongly pH-dependent, and lowering of pH caused release of nearly all cell associated radioactivity at 4 degrees C. In T- and B-lymphocytes, additional binding at high ligand concentrations was accounted for by receptors of much lower affinity. Binding to low-affinity receptors appeared reversible. At 4 degrees C, 2.2 pM labelled IL-2 (ala 125) bound to PHA-blasts (3.6 X 10(6)/ml) with a half time of about 15 min, and the association rate constant was approximately 8 X 10(9) M-1 min-1. The number of high affinity receptors per T-cell was determined as 9.7 +/- 0.5 X 10(2). At 37 degrees C, 60% of the tracer bound at 4 degrees C was rapidly internalized (Kint = 0.89 X 10(-1) min-1), and radioactivity comprising small MW products and iodotyrosine was released following a sigmoidal curve after a 20 min lag period. Similar results were obtained in PWM-activated B-lymphocytes and in cultured monocytes. It is concluded that high-affinity receptors mediate binding, uptake and degradation of IL-2 in activated human T- and B-lymphocytes and in monocyte-macrophages.

B-Lymphocytes↗
PubMed1987

HLA-DP and bone marrow transplantation: DP-incompatibility and severe acute graft versus host disease.

Thirteen recipients of HLA-haploidentical, DR compatible bone marrow (BM) and the corresponding BM donors were HLA-DP typed using primed lymphocyte typing (PLT). Severe acute GVHD (greater than or equal to grade 2) developed within 3 months after BM-transplantation in all of eight recipients of DP incompatible BM, but in none of five recipients of DP-compatible BM. This difference was highly significant (p less than 0.001, Fisher's exact test). Moreover, severe acute GVHD was significantly increased in recipients of haploidentical, DR compatible, but DP incompatible BM as compared to severe acute GVHD in 88 recipients of HLA-identical BM (p less than 0.0001). In contrast, there was no difference in acute GVHD between recipients of haploidentical, DR and DP compatible BM and recipients of HLA-identical BM. The data presented here provide strong evidence for the first time that HLA-DP antigens play a role as transplantation antigens.

Bone Marrow Transplantation↗
PubMed1987

HLA-DPw antigens in Danes and Eskimos as determined by local bulk PTL-reagents.

Primed Lymphocyte Typing cells (PLT-cells) with specificities for HLA-DP w1-w6 were generated. Responder and stimulator lymphocytes were from highly selected donors. Responder cells were primed twice (for 10 and 6 days respectively) prior to a third priming and bulk expansion in IL-2 containing medium. The coefficient of correlation between typing results obtained with local PLT-reagents and results based on 9th International Histocompatibility Workshop reagents was 0.91. As determined by batch to batch and day to day variations (different batch on different day), the reproducibility of +/- scorings and assignments obtained with local reagents was 0.87 (range 0.64-1.0) and 0.9 (range 0.69-1.0) respectively. The HLA-DPw gene frequencies in a population of 88 unrelated Danes and a population of 48 unrelated Greenland Eskimos were determined. The DPw gene frequencies observed in Danes were very similar to those reported in other Caucasian populations. Compared to Caucasians, a significantly lower frequency of DPw3 and a somewhat higher frequency of DPw2 were found in Eskimos. The findings did not differ from the Hardy-Weinberg expectations. No linkage disequilibrium between DR and DP was observed in the Eskimo population, whereas the DR3 - DPw1 association in Danes (Caucasians) was confirmed. With regard to HLA-DR, DR1, DR4 and DR7 were found to be more frequent in Eskimos than in Danes (not significant using corrected p values). The genetic distance between the Danish and Eskimo population was 0.21 as determined by DPw and 0.24 as determined by DR gene frequencies.

Asian People↗
PubMed1987

Application of an enzyme-linked immunoassay for the measurement of pregnancy zone protein (PZP) in cell culture supernatants and sera.

A simple and sensitive enzyme-linked immunosorbent assay (ELISA) measuring specifically the pregnancy zone protein (PZP) was constructed. The assay range was 2.0-500 micrograms/l. The intra-assay coefficient of variation (CV%) was 5.9% at the level of 100 micrograms/l and 3.5% at 10 micrograms/l. The imprecision between runs was 4.5% at 100 micrograms/l and 7.6% at 10 micrograms/l. Recovery of the native PZP standard added to serum-free cell culture medium was 98.1 +/- 3.7% (mean +/- SD), and recovery from serum of women in late pregnancy was 96.0 +/- 9.3%. Recovery from PZP-chymotrypsin (PZP-CT) complexes added to serum-free medium was 141 +/- 4.3%. There was no detectable cross-reactivity between the anti-human PZP antibody and human alpha 2-macroglobulin (alpha 2-M). The dose-response of two PZP standards and the PZP serum concentrations of 100 blood donors were determined. Furthermore, the serum level of PZP from 11 patients suffering from IgA myeloma was quantitated and found within the normal range when compared to serum levels of healthy blood donors of the same age and sex. Finally, supernatants from serum-free cultures of different human peripheral blood mononuclear cell (PBM) subpopulations were assayed. Neither of them were found to exhibit any detectable increase in PZP concentration during culture, but cultures of monocytes were found to produce alpha 2-M.

Blood↗
PubMed1985

Prolonged severe cholestasis induced by oxacillin derivatives. A report on two cases.

Two patients with osteomyelitis who developed reversible cholestatic jaundice during treatment with oxacillin derivatives are described. The clinical course as well as the biochemical pattern and the investigation of liver biopsy specimens enabled us to establish the diagnoses of drug-induced canalicular and hepatocanalicular cholestasis.

Adult↗
PubMed1984

Oral and intravenous acyclovir are equally effective in herpes zoster.

In a double-blind randomised trial 40 patients above 60 years old with acute herpes zoster received either 5 mg/kg acyclovir three times daily intravenously or 400 mg acyclovir five times daily orally for five days. Identical results were obtained with respect to duration of pain and rate of healing. Twenty per cent of orally administered acyclovir was absorbed and gave satisfactory concentrations of acyclovir in the vesicular fluid.

Acyclovir↗