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Biomedical subjects

M Onsrud

Publications and source records attributed to M Onsrud.

At least 55 records · Page 3Linked to original sources

Squamous cell carcinoma of the cervix stage IB: numbers and reactivities of pelvic lymph node T cells.

Ten patients with squamous cell carcinoma of the cervix stage IB (FIGO) treated by radical hysterectomy and pelvic lymph node dissection had node biopsies taken for immunological studies. There was no evidence of metastases. Node biopsies from near the cervix (the obturator region) contained significantly more lymphoid cells per gram of tissue than biopsies from more distant (common iliac) nodes. The percentage of T cells was similar in the two nodes, but significantly lower than in mononuclear cell suspensions from peripheral blood. All patients responded to the mitogen phytohemagglutinin. Positive T-cell responses to herpes simplex virus antigen were found in seven patients. Six patients responded to stimulation by the chlamydial antigen LGV-2. Lymph node T cells gave responses higher than those from peripheral blood T cells. Obturator node T cells from patients pretreated with intracavitary radium had antigen-specific responses lower than those of the patients operated without prior irradiation. The results indicate that the pelvic lymph nodes are important reservoirs for sensitized T cells.

Adult↗

Cell-mediated and humoral immune responses to chlamydial and herpesvirus antigens in patients with cervical carcinoma.

Herpes simplex virus (HSV) and Chlamydia trachomatis are both discussed in the etiology of cervical carcinoma. In this study the antibody titers and the T-cell proliferative responses to chlamydial and HSV antigens in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer, have been investigated and compared. The patients with CIN and invasive cancer showed approximately the same degree of immune responses to chlamydial and HSV antigens. Of the patients, 58% showed proliferative T-cell responses to C. trachomatis antigen, 87% to HSV antigens. Chlamydial antibodies were detected in 65% of the patients, while 81% had a positive HSV serology. Our results show a lack of correlation between levels of antibody titer and T-cell responses. It is concluded that patients with CIN and invasive cervical cancer have intact cellular immune responses to both chlamydial and HSV antigens. The eventual role of these infections in the etiology remains unclear.

Adenocarcinoma↗

Serum-mediated immunosuppression: a possible tumor marker in patients with ovarian carcinoma.

Serum samples from 25 patients with ovarian carcinoma were tested for their suppressive effects on in vitro response of normal lymphocytes. Patients examined prior to primary surgery showed a significantly greater suppression than did patients examined after a radical operation. Suppression was detected both in a natural killer cell assay and in an assay of phytohemagglutinin-induced lymphoproliferation. Only the results of the later test showed a correlation to the clinical course: Those patients who died during the first year of follow-up presented the most marked suppression. Serial determinations performed in a few patients indicated a certain correlation between immunosuppression and tumor burden. It is concluded that this test may give additional prognostic information in patients with ovarian carcinoma.

Antilymphocyte Serum↗

Serum lipids and lipoproteins in patients with endometrial carcinoma receiving adjuvant treatment with hydroxyprogesterone caproate.

Serum levels of triglycerides, total cholesterol, and HDL-cholesterol were determined in 57 patients who were undergoing treatment for stage I endometrial carcinoma. The patients belonged to a clinical trial where group A (control) was treated with surgery plus intravaginal irradiation, whereas group B in addition was treated with hydroxyprogesterone caproate (5000 mg i.m. as a loading dose followed by 1000 mg every 2 weeks for one year). In group B patients followed during the first 13 weeks of treatment, the level of serum triglycerides remained stable, whereas the level of total cholesterol and HDL-cholesterol increased significantly. This increase could not, however, have been caused by the progestogen treatment, as similar changes were seen in group A patients followed for the same period of time. Long-term effects were looked for in patient groups examined 3-12 months after the start of treatment and in groups examined 3-6 months after the hormone therapy was stopped. In neither group could any significant difference in cholesterol or HDL-cholesterol be found. It is concluded that this type of progestogen treatment causes no significant change in the levels of triglycerides, cholesterol, and HDL-cholesterol.

17 alpha-Hydroxyprogesterone Caproate↗

Intramuscular administration of hydroxyprogesterone caproate in patients with endometrial carcinoma. Pharmacokinetics and effects on adrenal function.

A radio-immunoassay for the determination of the serum concentration of hydroxyprogesterone caproate (HPC) was established. After a single intramuscular injection of 1000 mg, the mean serum level reached its maximum (44-81 nmol/l) after 2-7 days. Patients on long-term adjuvant HPC treatment (consisting of 1000 mg daily for 5 days followed by 1000 mg every 2 weeks) presented peak hormone levels 2 weeks after commencing treatment. After a drop at 5 weeks, the mean serum level slowly increased again to 130 nmol/l after 25 weeks of treatment. Patients being treated with weekly injections had significantly higher serum levels than those treated every 2 weeks. Considerable inter-individual differences were observed. The serum concentrations of HPC measured in this study compare favorably with those previously found in patients treated with medroxyprogesterone acetate. The patients on adjuvant HPC showed no significant change in the levels of cortisol, dehydroepiandrosterone sulphate, androstenedione, or estrone during the first 25 weeks of treatment.

17 alpha-Hydroxyprogesterone Caproate↗

Acquired immunodeficiency syndrome (AIDS). Clinical, immunological, pathological, and microbiological studies of the first case diagnosed in Norway.

The first case of acquired immunodeficiency syndrome (AIDS) in Norway, diagnosed in January 1983, is presented, with results of clinical, immunological, and microbiological studies and the results of autopsy. Immunological studies showed several immunological abnormalities, including a profound deficiency of the T-cell system of the type usually associated with AIDS. During the 11 months of symptomatic disease the patient had a series of opportunistic infections, including recurrent candida esophagitis, probable Pneumocystis carinii pneumonia, and severe and recurrent perioral Herpes simplex virus infection. During the last months he had increasing signs and symptoms of disseminated cytomegalovirus infection, which was probably the major cause of death, as revealed by autopsy. Autopsy also showed the presence of disseminated infection with a slowly growing, so far unclassified Mycobacterium species, and signs of a focal aspergillus pneumonia.

Acquired Immunodeficiency Syndrome↗

Influence of progestogen therapy on T lymphocyte subsets.

The distribution of T lymphocyte subsets was determined in 22 patients with endometrial carcinoma stage 1. Following surgery and postoperative radiotherapy the patients had been "randomized" into two groups: group A patients received no further treatment, whereas group B patients were treated with 17 alpha-hydroxyprogesterone caproate for one year. T cells and T cell subsets were estimated by an indirect immunofluorescence technique using the monoclonal antibodies UCHT3 (mature T cells), OKT4 (T helper cells), and OKT8 (T suppressor/cytotoxic cells). When examined 3-12 months after randomization the two groups had similar numbers of UCHT3+ cells and OKT4+ cells. Group B patients, however, had a significantly lower proportion of OKT8+ cells and hence a significantly higher OKT4/OKT8 ratio than group A patients. It is concluded that progestogen therapy has some immunomodulating effects.

Antibodies, Monoclonal↗

Natural killer cell activity after gynecologic infections with chlamydia.

The level of blood natural killer (NK) cell activity was determined in relation to chlamydial infections. A group of 10 women who had recovered from chlamydial salpingitis was compared with a similar group who had had chlamydial cervicitis. Ten healthy female blood donors with no history of chlamydial infections served as controls. The spontaneous cytotoxicity of non-adherent blood lymphocytes was determined in a 3-hour assay with radiolabelled K562 cells as targets. There were no significant differences in the NK cell activity of the three groups. No correlation between NK cell activity and chlamydial IgG antibody titer in serum could be found. The level of NK cell activity as determined in this system cannot explain why some patients get a more severe form of chlamydial infection than others do.

Adolescent↗

Depressed in vitro lymphoproliferation after radiation therapy. Influences of adherent cells, indomethacin, and autologous serum.

Mixed lymphocyte culture (MLC) responses and lymphocyte proliferative responses to phytohaemagglutinin (PHA) stimulation were determined before and after pelvic irradiation with 40 Gy in 10 patients with endometrial carcinoma stage I. The MLC responses were depressed after irradiation, and were not normalized after adherent cell depletion. Adherent cells did not significantly suppress the responses of non-adherent lymphocytes. Indomethacin could not restore the depressed PHA responses occurring after irradiation. Autologous posttreatment serum was not suppressive. The results favour the assumption that irradiation causes immunodepression by injuring the responding cells or some amplifier system, rather than by activation of suppressor systems.

Female↗

Effects of hyperthermia on human natural killer cells.

Lymphocytes from healthy blood donors were exposed to temperatures between 37 degrees C and 42 degrees C for up to three hours and then tested for natural killer (NK) activity using K562 cells as targets in a 3-h 51Cr-release assay. For a given level of hyperthermia a semilogarithmic decrease in NK activity relative to the treatment period was seen. NK effectors exposed to 42 degrees C for one hour lost 90% of their cytotoxic capacity compared to effectors kept at 37 degrees C. The depression in NK activity could Not be repaired by overnight incubation at 37 degrees C or by interferon treatment. Heating also inhibited the induction of NK-like cells during mixed lymphocyte culture (MLC), while exposure of either responder or stimulator cells to hyperthermia did not affect the degree of MLC-proliferation. The heating only slightly decreased lymphocyte viability--as determined by trypan blue exclusion--whereas a marked and permanent reduction in the number of cells bearing Fc-receptors for IgG occurred. The content of E-rosetting cells decreased initially, but was normalized after overnight incubation. The findings indicate that NK cells and T cells are differentially sensitive to in vitro hyperthermic treatment.

Cell Survival↗

Reduced generation of suppressor cells in human mixed lymphocyte culture after radiotherapy.

Suppressor T cells can be generated in mixed lymphocyte cultures (MLC) and their function is relatively resistant to irradiation in vitro. In this study the capacity to generate suppressor cells in MLC was determined before and after radiotherapy in 11 patients with endometrial cancer. After external pelvic radiotherapy with 40 Gy, the lymphocytes remaining in circulation demonstrated a lowered proliferation in MLC, and also the suppressive effect of MLC-activated cells was reduced. After radiotherapy, ten times as many MLC-activated cells were needed to get the same degree of suppression as before radiotherapy.

Cytotoxicity, Immunologic↗

Influence of in vivo diethylstilbosterol phosphate on some human blood lymphocyte sub-populations.

The effects of in vivo diethylstilbosterol phosphate (DES-P) on lymphoid cells were studied in six patients with adenocarcinoma of the prostate. The administration of 500 mg DES-P intravenously caused increased numbers of circulating granulocytes, monocytes, and non-T lymphocytes lasting for 24-48 hours. The natural killer activity, as measured in a three-hours 51Cr-release assay with K562 cells as targets, was transiently depressed four hours after drug injection. Parallel variations were found in the fraction of lymphocytes bearing receptors for the Fc part of IgG. In mixed lymphocyte culture (MLC) the responding capacity of the T cells and the stimulatory capacity of the non-T cells were unaffected. In vitro preincubation with DES-P overnight was not toxic to the lymphocytes. To be suppressive in MLC DES-P had to be added in concentrations one thousand times higher than those of hydrocortisone. It is concluded that a single dose of DES-P in vivo modulates the kinetics of recirculating lymphoid cells.

Aged↗

Enhancement of suppressor cell generation in human mixed lymphocyte cultures by interferon.

Mixed lymphocyte culture (MLC) interactions are differentially influenced by interferon: proliferation is reduced whereas the induction of allospecific cytotoxic cells is enhanced. The experiments presented here show that interferon also potentiates the induction of cells which suppress the MLC responsiveness of freshly prepared responding cells from the same donor. This effect is most evident when low doses of interferon and low numbers of suppressor cells are used, and it does not seem to be exerted by a cytotoxic mechanism. Maximum effect was seen with interferon present from the beginning of and throughout the induction period, and once the suppressor cells were generated, interferon did not further potentiate their function.

Cytotoxicity, Immunologic↗