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M Petersson

Publications and source records attributed to M Petersson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Oxytocin increases nociceptive thresholds in a long-term perspective in female and male rats.

Oxytocin (0.1 and 1.0 mg/kg s.c.) given to male rats during 5 days, increased tail-flick latency when measured 1 (P < 0.05) and 7 days (0.1 mg/kg, P < 0.05; 1.0 mg/kg, P < 0.01) after the last injection. The effect was gone 2 weeks after the end of the treatment. If an additional injection of oxytocin was given 10 days after a previous 5 day treatment period, the significant difference persisted after 3 weeks (P < 0.05). Tail-flick latency was significantly delayed also in oxytocin-treated females when measured 1 week after the treatment period (P < 0.05). Naloxone, but not an oxytocin antagonist, temporarily antagonised the oxytocin induced delay in withdrawal latency. This indicates that oxytocin may act by increasing the activity of opioid mechanisms.

Animals↗
PubMed1996

Hydrogen peroxide secreted by tumor-derived macrophages down-modulates signal-transducing zeta molecules and inhibits tumor-specific T cell-and natural killer cell-mediated cytotoxicity.

Although alterations in CD3-associated signal-transducing molecules in tumor-infiltrating T cells of patients with advanced cancer have been previously described, the mechanism behind these changes is not known. We demonstrate that macrophages isolated from metastatic lymph nodes of patients with malignant melanoma down-regulate levels of CD3 zeta in autologous peripheral blood T cells. Lipopolysaccharide (LPS)- or phorbol 12-myristate 13-acetate (PMA)-stimulated monocytes derived from peripheral blood of healthy donors also induced decreased expression of CD3 and CD16-associated zeta chains similar to that observed in T cells and natural killer (NK) cells of patients with advanced cancer. Co-culture with activated monocytes impaired Ca2+ mobilization in peripheral blood derived-T cells when stimulated with monoclonal antibodies to CD3 and also strongly inhibited melanoma-specific cytotoxic T lymphocyte (CTL) activity and NK activity. The presence of catalase, a scavenger of H2O2, during co-culture almost totally abrogated the inhibitory effect of activated monocytes on melanoma-specific CTL lines and on NK cells. Pre-treatment of CTL or NK cells with nontoxic concentrations (1 x 10(-5) M) of H2O2 also severely reduced their cytotoxic activity which could be prevented by catalase. The decrease in CD3 zeta and in CD16 zeta expression, induced by macrophages isolated from metastatic lymph nodes or by LPS-stimulated monocytes, was also prevented by catalase when maintained throughout the co-culture period. The possibility that monocyte/macrophage-derived reactive oxygen metabolites contribute directly to alterations in signal transducing molecules of T cells and NK cells and to the mechanism of immunosuppression in individuals with cancer should be considered.

CD3 Complex↗
PubMed1996

Oxytocin causes a long-term decrease of blood pressure in female and male rats.

The aim of the present study was to investigate the long-term effects of oxytocin (OXY) on blood pressure (BP) and heart rate (HR) in conscious female and male rats. For this purpose, subcutaneous (SC) (0.01, 0.1, and 1 mg/kg) or intracerebroventricular (ICV) (1 microgram/kg) injections of OXY were given during 5-day periods. BP and HR were measured daily. A significant decrease in BP, without affecting HR, compared to saline-treated controls was seen in response to 0.1 (males: p < 0.01, females: p < 0.001) and 1 mg/kg (p < 0.001) of OXY given SC. BP gradually returned to preexperimental levels within 10 days after the last injection in male rats but, in females, the significant lowering of BP remained unchanged during this period. Also OXY ICV (1 microgram/kg) decreased BP (p < 0.05 after one day, p < 0.001 after 5 days of injections). This effect was still present 8 days after the last injection (p < 0.05). These results indicate that OXY may induce a long-term lowering of BP.

Animals↗
PubMed1996

Decreased expression of signal-transducing zeta chain in peripheral T cells and natural killer cells in patients with cervical cancer.

An impaired immune response is frequently observed in patients and experimental animals with advanced cancer. We and others have shown alterations in CD3-associated signal-transducing zeta molecules in tumor-infiltrating T cells and peripheral blood lymphocytes (PBLs) of patients with advanced cancer. By using flow cytometric analysis of permeabilized cells with a monoclonal antibody (TIA-2) that reacts with the cytoplasmic domain of the zeta chain, here we demonstrate a marked decrease (P < 0.01) in the expression of the signal-transducing CD3 zeta chain of PBLs in patients with cervical cancer (n = 22) as compared to PBLs from healthy donors (n = 21). In addition, PBLs isolated from patients (n = 23) with cervical intraepithelial neoplasia (CIN), to a lesser but significant (P < 0. 01) extent, expressed reduced CD3 zeta levels as compared to those from healthy donors. This decreased expression of zeta chains was also observed on CD16(+) natural killer cells in PBLs from patients with cervical cancer. Surface expression of CD3 epsilon on PBLs was also decreased in cervical cancer patients as compared to healthy donors, but not on PBLs from patients with CIN. CD3 zeta chain expression significantly (r = 0.53, P < 0.01) correlated with the ability of the PBLs to produce tumor necrosis factor in response to anti-CD3 stimulation. These findings suggest that alterations of signal-transducing zeta molecules commonly occur in patients with cervical cancer and to a lesser extent with CIN, and that they are associated with reduced cellular functions such as production of tumor necrosis factor.

Antibodies, Monoclonal↗
PubMed1995

Methylcholanthrene-induced mouse sarcomas express individually distinct major histocompatibility complex class I-associated peptides recognized by specific CD8+ T-cell lines.

Mouse sarcomas induced by methylcholanthrene (MC) are immunologically distinct even if they are induced in the same strain of mice. T-cell lines were derived from mice immunized against a series of syngeneic MC sarcomas on B6 background, known to carry unique tumor-specific transplantation antigens. Tumor necrosis factor-alpha (TNF-alpha) release assays concurred with the in vivo rejection tests. The strongest response in the TNF-alpha release was always obtained with the corresponding tumor, with very limited cross-reactivity against five other MC tumors or two virally induced B6 lymphomas. The specific TNF-alpha release from the anti-MC tumor CTL lines was mainly mediated by CD8+ cells. T-cell lines from intact and CD4-/- mice gave a similarly specific pattern. In contrast, T-cell lines derived from CD8-/- mice cross-reacted with several other MC-induced tumors. Peptides eluted from MC sarcomas under mild acid conditions were fractionated by reverse-phase high performance liquid chromatography and tested for their ability to sensitize the processing- and presentation-defective mutant RMA-S line. Only one high performance liquid chromatographic fraction from each of the three different tumor-derived peptide eluates capacitated RMA-S to induce TNF-alpha release and sensitized the cell to the cytotoxic effect of the corresponding tumor-specific T-cell line. A different Kb-restricted peptide fraction was active for each of the three MC sarcomas tested, indicating that they all expressed individually distinct peptide epitopes.

Animals↗
PubMed1995

Bradykinin-induced release of thromboxane B2 into bronchoalveolar lavage fluid of guinea pigs: relationship to airflow obstruction.

The aim of this study was to evaluate the role of thromboxane A2 in bradykinin-induced airflow obstruction in guinea pig in vivo. Airway insufflation pressure (Pi) was measured to assess airflow obstruction and the thromboxane B2 (a stable metabolite of thromboxane A2) concentration in bronchoalveolar lavage fluid was determined by radioimmunoassay. The animals were pretreated with propranolol (1 mg/kg i.v.) and suxamethonium (5 mg i.v.) prior to bradykinin administration. Bradykinin instillation into the trachea (300 nmol) induced a Pi increase (47.5 +/- 8.3 cm H2O versus 23.8 +/- 1.5 in sham) and significant thromboxane B2 release into bronchoalveolar lavage fluid (79 +/- 19 pg/ml versus 19 +/- 6 in sham). A thromboxane synthase inhibitor (OKY-046, 30 mg/kg i.v.; ((E-E)-3-[p(1H-imidazole-1-yl-methyl) phenyl]-2-propenoic acid hydrochloride mono-hydrate)) or a thromboxane A2 receptor antagonist (ICI192,605, 0.5 mg/kg i.v.; (4-(Z)-6-(2-o-chloro-phenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl) hexenoic acid)) reduced the Pi increase evoked by bradykinin (38.7 +/- 3.8 and 40.6 +/- 3.8 cm H2O, respectively). OKY-046 abolished the thromboxane B2 release. A platelet-activating factor receptor antagonist, WEB2086 (1 mg/kg i.v.; (3-[4-(chlorophenyl)-9-methyl-6H-thienol [3,2-f][1,2,4]trizolo-[4,3-a][1,4] diazepin-2-yl]1-4-(4-morpholinyl)-1-propanon) did not significantly affect any measured parameter. We conclude that, in guinea pigs, bradykinin-induced airway effects are associated with a local thromboxane A2 release.

Airway Obstruction↗
PubMed1995

IL-10 converts mouse lymphoma cells to a CTL-resistant, NK-sensitive phenotype with low but peptide-inducible MHC class I expression.

IL-10 has a variety of effects including: inhibition of monocyte MHC class II-dependent Ag presentation, Th1 cytokine production, and inhibition of T cell proliferation. Recently we have shown that IL-10 inhibits Ag presentation to human tumor-specific and allospecific CTL. In the present study we showed that transfection of the mouse lymphoma RMA (H-2b) with the IL-10 gene induced conversion to a RMA-S-like phenotype. The changes included an inhibition of lysis by minor histocompatibility or tumor Ag-specific CTLs and, conversely, a dramatic increase in susceptibility to lysis by NK cells. The RMA-10 transfectants showed levels of H-2 expression as low or even lower than those found on RMA-S. The levels of tested adhesion molecules were unaltered. Treatment of RMA with rIL-10 gave a less pronounced change in phenotype. In addition, relative to untreated target cells, IL-10 pretreated cells or IL-10 transfectants were unaltered in their capacity to affect cytotoxicity by cold target inhibition, arguing against the possibility that the observed effect could be a direct effect of IL-10 on the CTL. The expression of H-2 was partially restored by coculturing RMA-10 transfectants with class I-binding peptides. Taken together, these results indicate that IL-10 exerts a post-transcriptional effect on H-2 expression, compatible with an induced decrease in the access of peptides to the MHC class I complex. IL-10 is the first cytokine reported to have this effect and also the first factor shown to induce NK sensitivity and reduced sensitivity to CTL, an effect that may be of physiologic relevance.

Animals↗
PubMed1995

Alterations in the signal-transducing molecules of T cells and NK cells in colorectal tumor-infiltrating, gut mucosal and peripheral lymphocytes: correlation with the stage of the disease.

T cells from mice bearing an experimental colon carcinoma, and from patients with colorectal and renal carcinomas, have atypical T-cell receptors (TCR). In the present study, further characterization of modulations in CD3- and CD16-associated zeta chain in peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) from colorectal carcinomas was performed. Relative to PBL, the percentage of natural killer (NK) cells among fresh TIL was reduced, while a higher proportion of T cells expressing HLA-DR was found. As previously reported, we found significantly reduced levels of the CD3- and CD16-associated zeta chain in TIL and, to a lesser extent, also in patients' PBL. Levels of zeta chain in T and NK cells from non-cancerous colorectal tissue from patients were lower than in PBL but higher than in TIL, with a direct relationship between levels of this signal-transducing molecule and the distance from the tumor. In addition, zeta levels correlated with the Dukes' stage of the disease, since PBL from patients with lymph-node involvement or distant organ metastases (Dukes' stages C and D) had significantly less CD3 zeta than patients with localized disease (stages A and B). Patients' T cells also had decreased levels of cell-surface and cytoplasmic CD3 epsilon. We also observed reduced levels of the TCR accessory molecules CD4 and CD8, mainly on TIL but to a lesser extent also on patients' PBL. Biochemical analysis of anti-CD3 epsilon-immunoprecipitated TCR complexes demonstrated that the CD3 complex was not associated with the zeta chain, either on TIL or on PBL or on lymphocytes from non-cancerous colon tissue, suggesting a defect in the assembly of the TCR complex. Following several days of in vitro culture with recombinant interleukin-2 and phytohemagglutinin, anti-CD3 or anti-CD2 monoclonal antibodies (MAbs), levels of CD3 zeta chain as well as of cell surface CD3 epsilon were normalized. Our findings suggest an abnormal expression as well as assembly of several different signal-transducing molecules of T cells and NK cells, which correlate with the stage of the disease in patients with colorectal carcinomas.

Adult↗
PubMed1994

Interleukin 10 pretreatment protects target cells from tumor- and allo-specific cytotoxic T cells and downregulates HLA class I expression.

Interleukin 10 (IL-10) is a cytokine with a variety of reported effects including inhibition of monocyte major histocompatibility complex (MHC) class II-dependent antigen presentation, type 1 helper T cell cytokine production, and inhibition of T cell proliferation. Herein we report the effect of IL-10 pretreatment on antigen presentation to tumor- and allo-specific CD8+ cytotoxic T lymphocytes (CTL). Prior incubation of human melanoma cells with recombinant IL-10 (rIL-10) for 48-72 h resulted in a dose-dependent, up to 100% inhibition, of autologous CTL-mediated, HLA-A2.1-restricted, tumor-specific lysis. Allo-specific CTL cytotoxicity against Epstein-Barr virus-transformed lymphoblastoid cell lines (LCL) was also inhibited, demonstrating a protective effect also on lymphoid cells. In contrast, IL-10 pretreatment of allogeneic LCL or K562 targets had either no effect or slightly enhanced cytotoxic activity mediated by freshly isolated or IL-2-activated natural killer cells. Flow cytometric analysis with monoclonal antibodies against HLA-A2, or nonpolymorphic determinants of MHC class I proteins, revealed a 20-50% reduction in cell-surface expression, whereas intercellular adhesion molecules 1, and 2, and lymphocyte function-associated antigen 3 levels were not affected. In addition, relative to untreated target cells, IL-10 pretreated tumor cells were unaltered in their capacity to affect CTL-mediated lysis by cold target inhibition, demonstrating that the effect of IL-10 is unrelated to the initial binding of CTL to their targets. These results are compatible with an effect of IL-10 on the MHC class I antigen presentation pathway, and suggest a novel mechanism of immune tolerance, based on escape from CTL-mediated tumor and allo-transplant rejection.

Antibodies, Monoclonal↗
PubMed1994

[Therapeutic need of acute psychiatric patients and offered care during a 10-year period].

With reference to the great changes made in recent years within the Danish psychiatric services, we compared the demand for care of acute psychiatric patients with the care offered. Over a period of three months in 1991 we prospectively registered all 243 acute psychiatric referrals to Svendborg Hospital, with regard to age, sex, way and source of referral, diagnosis, need for care and care offered. The result was compared with similar surveys in 1980 and 1985. We found that optimal treatment was not available to approximately 20% of the acute psychiatric referrals, the care we most often were unable to offer was acute admission to the psychiatric ward of Svendborg Hospital. We also found that from 1980 to 1991 there were no changes in the number of daily referrals, in the sex ratio or the age distribution of the patients. Our ability to meet the specific needs for care changes quantitatively throughout the period. The survey concludes that we are still unable to meet the specific needs for treatment of acute psychiatric referrals. Various suggestions are made as to how to improve the services offered to acute psychiatric patients.

Acute Disease↗
PubMed1993

Decreased expression of the signal-transducing zeta chains in tumor-infiltrating T-cells and NK cells of patients with colorectal carcinoma.

An impaired immune response is frequently observed in cancer patients and tumor-bearing mice. T-cells from mice with an experimental colon carcinoma were recently shown to express T-cell receptors that completely lacked the signal-transducing molecule CD3 zeta. Here, we have investigated the expression of the signal-transducing molecule zeta on lymphocytes from 14 patients with colorectal carcinomas using flow cytometric analysis of permeabilized cells with a monoclonal antibody (TIA-2; IgG1) specific for the cytoplasmic domain of the zeta chain as well as with immunoprecipitation and analysis on diagonal gel electrophoresis. We demonstrate that T-cells isolated from the tumors of the patients express significantly less CD3 zeta than T-cells in the peripheral blood of the same patients and that the peripheral blood of the patients express decreased levels of zeta chains, as compared to the levels found in lymphocytes from healthy controls. This decreased expression was also observed on zeta chains associated with the low affinity Fc receptor for IgG found in tumor-infiltrating NK cells (Fc gamma RIIIA alpha; CD16).

Colorectal Neoplasms↗
PubMed1993

Immunization against tumor and minor histocompatibility antigens by eluted cellular peptides loaded on antigen processing defective cells.

Material eluted from RMA lymphoma or B6 spleen cells under acid conditions was fractionated by reverse phase high-performance liquid chromatography, and tested for ability to restore the sensitivity to cytotoxic T lymphocytes of the processing/presentation defective mutant line RMA-S. This allowed identification of three fractions (termed M1, M2 and M3) carrying B6 antigens recognized by cytotoxic T lymphocytes (CTL) elicited across the minor histocompatibility barrier A.BY anti-B6 (both H-2b) and one fraction (termed T1) carrying a tumor antigen recognized by B6 anti-RMA CTL. By parallel runs of material from cell lysates over major histocompatibility complex class I affinity columns, the M2 and M3 antigens were defined as Kb restricted, and M1 and T1 as Db restricted. Isolated fractions loaded onto RMA-S cells could be used to prime anti-minor histocompatibility antigen and tumor CTL in vivo. They could also be used for in vitro restimulation of spleen cells from mice that had been primed either by antigen-loaded RMA-S, or by wild-type RMA tumor cells and B6 splenocytes. The CTL generated by these methods were specific for the loading antigen, and they also recognized the antigen on the "physiological" target, i.e. RMA or B6 lymphoblasts. This system based on RMA-S as an immunization and target antigen reporter cell may be used for dissection of complex CTL responses, e.g. in studies of clonal composition and epitope dominance, or for studies of tumors that are poor stimulators of immunity.

Animals↗
PubMed1993

Regulation of lymphocyte aggregation and proliferation through adhesion molecule CD54 (ICAM-1).

The effect of two mouse mAb (LB-2 and G1B2) against human CD54 (intercellular adhesion molecule-1, ICAM-1) in lymphocyte aggregation and proliferation systems was investigated. The LB-2 mAb, but not G1B2, inhibited phorbol ester-induced aggregation of B lymphoblastoid cells. In addition, LB-2, but not G1B2, induced aggregation and proliferation of peripheral blood mononuclear cells (PBMC) in cultures containing FCS. The Fab fragment of LB-2 always (10/10 donors) induced proliferation while the intact mAb was active in 3/11 donors. When cultures contained human serum (HS), LB-2 and its Fab fragment induced proliferation in 1/9 and 1/4 donors, respectively. Addition of HS to FCS cultures inhibited proliferation induced by LB-2 Fab, indicating the presence of an inhibitory factor in human serum. Addition of anti-CD18 mAb to cultures stimulated by LB-2 Fab caused partial inhibition of proliferation but did not prevent aggregate formation. A combination of anti-CD18 and anti-CD29 mAb resulted in a nearly complete inhibition of proliferation but did not inhibit aggregate formation. In these experiments it was found that the anti-CD29 mAb 4B4 in itself induced cell aggregation of PBMC and enhanced aggregation induced by the anti-CD3 mAb OKT3. Both LB-2 and G1B2 showed significant inhibition (> 60%) of proliferation when human PBMC were stimulated by the antigen PPD in the presence of HS, but not when stimulated by staphylococcal enterotoxin A (SEA) or IL-2. This study describes two mAb against separate epitopes on CD54 which are differentially involved in cell aggregation or induction of proliferation but are of similar importance in antigen-specific responses. Furthermore, the new finding that the LB-2 mAb or its Fab fragment can induce cell aggregation and proliferation defines a signaling function of CD54 which may work independent of crosslinking or costimulation.

Animals↗
PubMed1992

Autonomic cardiovascular responses to tilting in patients with Alzheimer's disease and in healthy elderly women.

The cardiovascular responses to tilting and breathing were studied in 24 patients with late-onset Alzheimer's disease (AD) and 54 healthy control women aged between 75 and 96 years in order to study the parasympathetic and sympathetic heart-rate control. The cardiovascular response to tilting and breathing showed no age-associated decrease in the healthy control women. During rest, the AD patients had lower mean systolic and diastolic blood pressure but the same heart rate as the control patients. After tilting, the AD patients had a greater increase in heart rate, and the mean systolic blood pressure fell to 126 mmHg compared with 160 mmHg in the control women (p less than 0.001). After the initial acceleration, the following deceleration of the heart rate, an expression of parasympathetic nervous activity, was lower in the AD patients (p less than 0.001). The deep-breathing test showed no significant difference between the two groups, but the changes of acceleration and brake indices could indicate a dysfunction of the autonomic nervous system since the AD patients were not recumbent.

Aged↗
PubMed1988

In vivo function of natural killer cells as regulators of myeloid precursor cells in the spleen.

In order to study the in vivo effect that natural killer (NK) cells may have on hematopoietic precursor cells in the autologous host, NK-depleted mice were constructed by injection of an anti-NK-1.1 monoclonal antibody. Only the spleen, and not the bone marrow, of such NK-depleted mice shows an increase in the number of myeloid precursur cells able to form colonies in soft agar as compared to control mice with normal levels of NK activity. The increase in number of hematopoietic immature cells due to lack of a regulatory cell (i.e. NK cell) is selective for the committed myeloid precursur cells, and not evident for erythroid or pluripotent progenitor cells. This is direct evidence in support of the hypothesis that NK cells in the autologous host serve as a regulator of extramedullary myelopoiesis.

Animals↗
PubMed1987

Interferon gamma induces lung colonization by intravenously inoculated B16 melanoma cells in parallel with enhanced expression of class I major histocompatibility complex antigens.

Treatment of H-2-deficient nonmetastatic B16 melanoma cells with physiological doses of interferon gamma (IFN-gamma) reduced cellular growth in vitro but induced a shift to the lung-colonizing phenotype as assessed after intravenous injection of the treated cells. As little as 1 antiviral unit of recombinant IFN-gamma per ml induced B16 cells to form 3-40 pulmonary metastases in each injected mouse, whereas a 1000-fold higher concentration of IFN-beta was required to see similar effects. IFN-gamma may induce cell-surface molecules that contribute to the metastatic ability of the tumor cells. The efficient enhancement of metastatic ability after IFN-gamma treatment of the B16 cells was paralleled by an increased H-2 antigen expression and decreased sensitivity to natural killer cells. The experiments support the idea that metastasis may not depend exclusively on stable genetic changes or heterogeneity within a tumor population but may be also influenced through the modulation of the phenotype by physiological or pharmacological agents. The results are also discussed with regard to the role of different effector cells in tumor cell clearance and in relation to lymphokine-based strategies for therapy.

Animals↗
PubMed1986

Genetic studies on a tumor growth-inhibitory factor in serum of normal mice and its relationship to NK activity.

It has been shown that normal mouse serum contains a tumor growth-inhibitory factor (GIF). and that strain-dependent levels of GIF correlate with mouse NK activity. To further analyze the genetic control of GIF we have studied the growth-inhibitory activity of normal mouse serum from 8 different mouse strains and their F1 hybrids. A sensitive method using a chromogenic substrate for an endogenous lysosomal enzyme was used to measure the inhibitory activity of normal mouse serum on the mouse B16 melanoma. The highest level of GIF was found in old mice, lower activity in serum of young animals and no activity in suckling mice. To compare the genetic control of GIF and NK, spleen NK activity against B16 as well as YAC-1 targets was measured in parallel in the same animals. Confirming previous results we found the H-2k strains CBA and C3H to have high levels of GIF as well as NK activity, while the strain A/Sn and the A congenic strain A.SW had low levels of both activities. Experiments with H-2d and H-2b strains, however, showed that GIF and NK had a different genetic control; thus the DBA/2 and Balb/c strains had considerably higher GIF activity than the C57B1 and Leaden strains, while the reverse was true for NK activity. In F1 hybrid crosses between strains with high and low activity, high activity was inherited as a dominant trait for both GIF and NK. A backcross analysis in (A X CBA) X A backcross mice, segregating for NK and GIF showed that the two activities did not cosegregate. These studies therefore demonstrate that GIF and NK activity are under different genetic control, and do not support any direct or simple relationship between GIF and NK cells.

Animals↗