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T Kalland

Publications and source records attributed to T Kalland.

At least 127 records · Page 7Linked to original sources
PubMed1983

3-methylcholanthrene: transient inhibition of the lytic step of mouse natural killer cells.

Female mice belonging to NMRI stock were inoculated neonatally with daily doses of 5 micrograms diethylstilbestrol (DES) or olive oil for the first 5 days after birth and in adult life with 20 or 100 micrograms 3-methylcholanthrene (MCA) or the vehicle tricaprylin only. The cytotoxic activity of spleen natural killer (NK) cells against YAC-1 target cells was studied in a 51Cr release assay at 2, 5, 10, or 15 days after the MCA injection. A dose of 20 micrograms MCA to neonatally olive oil-injected females did not influence the NK activity, whereas an injection of 100 micrograms MCA significantly depressed the NK activity to about half the value seen in controls. This suppression was transient, and the normal level was reached again 15 days after the injection. The depressed NK activity could not be related to humoral or cellular suppressor mechanisms. A study at the single-cell level revealed that the inhibition was due to interference with the lytic step of the NK cell without affecting target-binding capacity. In vitro exposure of spleen cells from MCA-treated animals to interferon fully restored the NK activity. Neonatal DES treatment resulted in a depressed NK activity in adult females to a level about half of that seen in olive oil-injected controls. The NK activity in DES-treated females was not influenced by either 20 or 100 micrograms MCA. The MCA-induced suppression of NK activity was discussed in relation to the earlier reported difference in incidence of MCA-induced sarcomas between DES-treated and control females after they were given 20 micrograms MCA in adult life, as well as in relation to the same incidence in the 2 groups treated with 100 micrograms MCA. The results are compatible with a significant role for NK cells during MCA carcinogenesis and indicate that a possible part of the tumorigenic effect of MCA is its early suppressive effect on NK cell activity.

Aging↗
PubMed1983

Effects of in vitro hyperthermia on human natural killer cells.

The present study demonstrates that human natural killer (NK) cells isolated from peripheral blood of normal individuals are highly sensitive to hyperthermia. The effect was time and dose dependent, and treatment of peripheral blood lymphocytes at 42 degrees for 1 hr almost completely abolished NK activity. The effect was not a consequence of cell death since only a small decrease in cell viability was observed and the viability of density gradient fractions enriched for NK activity was normal. Analysis of NK activity at the single-cell level by application of a conjugation assay in agarose revealed that hyperthermia interfered with target cell binding as well as the lytic cycle. Attempts to rescue NK activity after hyperthermia treatment by incubation overnight with human alpha-interferon or activation in mixed leukocyte culture was unsuccessful, indicating that even pre-NK cells are heat sensitive. In contrast, the proliferative response to alloantigens in mixed leukocyte culture and to the T-cell mitogen concanavalin A was unaffected. Hyperthermia exposure of cytotoxic T-lymphocyte generated in mixed leukocyte culture immediately before assay against allogeneic blast cells strongly inhibited their activity. Some alterations in the kinetics of stimulation with the B-cell mitogen Staphylococcus aureus bacteria were observed after heat exposure although maximal stimulation was at control levels. Thus, NK cells, including their precursors, seem to be preferentially sensitive to hyperthermia among various lymphoid subclasses.

Cells, Cultured↗
PubMed1982

Effect of diethylstilbestrol and estramustine phosphate (Estracyt) on delayed hypersensitivity response to oxazolone in male mice.

The effects of diethylstilbestrol (DES) and estramustine phosphate (EMP) on delayed hypersensitivity response (DTH) to oxazolone in male mice were investigated using a radioisotopic ear method. DES significantly inhibited the ability to express a DTH response and was most effective when given during the effector phase of the reaction. EMP had no effects when the animals were exposed to the drug during the effector phase, while it resulted in a strong and dose-dependent depression of the DTH response when applied in the sensitization phase. Possible involvement of suppressor cells was investigated by pretreatment of animals with cyclophosphamide or by adoptive transfer of tentative suppressor cells from spleen, lymph nodes, or peritoneal cavity. However, no evidence of cellular or humoral suppressor factors induced by drug treatment was found.

Animals↗
PubMed1982

In vitro and in vivo effects of diethylstilbestrol and estramustine phosphate (Estracyt) on the mitogen responsiveness of human peripheral blood lymphocytes.

The responsiveness to diethylstilbestrol (DES) and estramustinephosphate (EMP) of human peripheral blood lymphocytes to T-cell mitogens has been investigated in vitro and in vivo. EMP demonstrated potent inhibition of both Con A- and PHA-induced lymphocyte proliferation in vitro, while it had no detectable effects when given to patients with cancer of the prostate. DES reduced the response to Con A in vitro, but had only marginal effects on PHA-induced mitogen response. In contrast, the response to Con A was unaltered, while the response to PHA was significantly diminished after DES therapy in patients with prostatic cancer. This effect, however, was only seen when high doses of DES not included in conventional regimen were given. The proliferative response to T-cell mitogens in patients with prostatic cancer was not affected by serum source in the assay, indicating the absence of humoral factors able to inhibit mitogen response in these patients.

Adult↗
PubMed1982

Effects of diethylstilbestrol and estramustine phosphate (Estracyt) on lymphoid cell populations and mitogen responsiveness in male mice.

Concentrations of diethylstilbestrol phosphate (DES-P) and estramustine phosphate (EMP) above 10(-5) M in cultures of spleen lymphocytes from adult male mice resulted in a dose related inhibition of both Con A and LPS induced lymphocyte proliferation. Male mice injected with 5.6 mg./kg. DES daily for 7 days had a significantly reduced responsiveness to both Con A and LPS compared to mice injected with olive oil only. Spleen lymphocytes from male mice treated with 100 mg./kg. EMP showed a reduction of Con A induced mitogenesis whereas they exhibited a significantly enhanced response to LPS. The effects of DES and EMP on Con A and LPS induced blastogenesis were abolished within 2 weeks after cessation of treatment. DES treatment resulted in preferential depletion of splenic and lymph node T lymphocytes and a disproportionate T lymphocyte subpopulation with respect to Ly subclasses. Exposure to 30 or 100 mg./kg. EMP resulted in a dose related loss of mononuclear cells both in spleen and lymph nodes. T lymphocytes predominantly of the Ly 1 phenotype were most sensitive to EMP. Co-cultures of spleen lymphocytes from normal mice and Mitomycin C blocked spleen cells from either normal of treated mice (DES or EMP) gave no convincing evidence of suppressor cell activity in the population of spleen mononuclear cells.

Animals↗
PubMed1982

Augmentation of natural killer cell activity after arterial embolization of renal carcinomas.

Preoperative embolization of the renal artery has been reported to improve the survival of patients with advanced renal carcinomas compared to operative treatment only. To investigate possible immunological consequences of tumor embolization, natural killer (NK) cell activity in peripheral blood was investigated immediately before and at different time intervals after occlusion of the renal artery by insertion of a metal coil. A slight increase in NK activity could be observed 24 hr postembolization while a marked augmentation was seen after 48 hr. The high NK activity persisted up to 96 hr after embolization, the last time period included in the study. Two patients undergoing the same procedure but in whom embolization was unsuccessful showed no alteration in NK activity. It is suggested that interferon produced by macrophages activated by the necrotizing tumor might be responsible for the augmentation of NK activity.

Aged↗
PubMed1981

Effect of treatment with diethylstilbestrol-polyestradiol phosphate or estramustine phosphate (estracyt) on natural killer cell activity in patients with prostatic cancer.

We evaluated the effect of treatment of patients with prostatic cancer with estramustine phosphate or the combination diethylstilbestrol-polyestradiol phosphate on the natural killer cell activity in peripheral blood. Although estramustine phosphate did not affect natural killer cell activity, diethylstilbestrol-polyestradiol phosphate substantially reduced natural killing after a treatment period of 1 week. The activity was only slightly further lowered after 4 weeks of treatment. Possible clinical implications of the difference in susceptibility of natural killer cells to these agents are discussed.

Aged↗
PubMed1981

Natural killer cell activity and tumor susceptibility in female mice treated neonatally with diethylstilbestrol.

Female NMRI or AKR/J mice were given daily s.c. injections of 5 micrograms diethylstilbestrol (DES) in 0.025 ml olive oil, or of olive oil only, for the first 5 days after birth. At the age of 6 to 7 weeks, both DES-treated females and control females were killed, and the cytotoxic activity of the spleen cells against standard natural killer cell target YAC-1 cells as well as the natural killer cell-sensitive I-522 cells and relatively insensitive I-51 AKR lymphomas were tested. The cytotoxic activity against I-51 cells was similar for DES-treated and control females while the DES-treated females had only about one-half the cytotoxicity activity to I-522 and YAC-1 cells as did controls. Control females eliminated radioactivity derived from 125I-labeled YAC-1 and I-522 target cells injected i.v. faster than did DES-treated females, while the results were similar for both animal groups when using I-51 cells. The cumulative death incidence was higher for DES-treated females than for control females after incubation with low numbers of I-522 cells but similar for both groups when using I-51 cells. Finally, the incidence of females developing methylcholanthrene-induced sarcomas, using a simple low-dose injection (10 or 20 micrograms), was higher among DES-injected animals than among controls. Taken together, the results indicate that female mice treated neonatally with DES have a functionally defective natural killer cell population, resulting in increased tumor susceptibility.

Animals↗
PubMed1981

Neonatal estrogen treatment and epithelial abnormalities in the cervicovaginal epithelium of adult mice.

Female NMRI mice were given injections of different doses of 17 beta-estradiol, 17 alpha-estradiol, diethylstilbestrol (DES), dienestrol, trans-stilbene, progesterone, testosterone, 5 alpha-dihydrotestosterone, or olive oil for the first 5 days after birth. When the females were killed at 8 weeks after birth, all the estrogens, effective at different dose levels (10(-2) to 5 microgram/day), had resulted in the display by several of the cervicovaginal preparations studied of a heterotopic columnar epithelium (HCE) in regions where females given injections of olive oil, testosterone, 5 alpha-dihydrotestosterone, progesterone, or trans-stilbene had only the normal squamous epithelium. The further fate of the HCE was followed at two later age stages, 36 to 52 weeks and 14 to 17 months. The HCE developed into glandular-like structures penetrating into the stroma and justifying the designation of adenosis. DES resulted in a more pronounced adenosis than did 17 beta-estradiol; in both cases, metaplasia was a striking component of the adenosis regions. Development of adenosis from HCE was dependent upon presence of the ovaries. Some preparations from 44-week-old females given DES injections showed signs of a beginning malignant transformation in the adenosis regions, more evident in 17-month-old females. Among the 23 preparations in the latter group, 8 had changes morphologically indicating malignancy with examples of adenocarcinoma, mixed carcinoma, and squamous carcinoma. Because of the seemingly low aggressive nature of this malignancy, the term "pseudocarcinoma" is discussed. Ten- to 12-week-old BALB/c and C57BL/6 females given DES injections neonatally had HCE in the uterine cervix and vaginal fornices after neonatal DES injections. Differences in extension of HCE were observed after DES injections for three different 5-day periods in th neonatal and immature stages of NMRI females. An interaction between different DES-sensitive parameters to result in the pseudocarcinomas is discussed.

Age Factors↗
PubMed1980

Ovarian influence on mitogen responsiveness of lymphocytes from mice neonatally exposed to diethylstilbestrol.

Treatment of neonatal female mice with diethylstilbestrol (DES) resulted in a reduced response of spleen lymphocytes to concanavalin A (Con A) and lipopolysaccharide (LPS). Ovariectomy or ovariectomy plus estradiol treatment had no influence on the response to Con A in either control or DES-treated females. Ovariectomy reduced the response to LPS in control animals and eliminated the difference between control and DES-treated females. Estradiol treatment enhanced the response of ovariectomized control females to LPS and restored the difference between control and DES-treated animals. Comparison of the mitogen responsiveness during various stages of the estrous cycle showed a tendency for the response to be augmented at proestrus and metestrus, although the differences were not significant.

Animals↗
PubMed1980

Long-term effects of neonatal DES treatment on plasma prolactin in female mice.

Prolactin was measured with a homologous radioimmunoassay in plasma samples from adult female NMRI mice injected with 5 micrograms diethylstilbestrol (DES females) or olive oil for the first five days after birth. Estradiol treatment of 6-month-old ovariectomized DES females resulted in markedly higher plasma prolactin concentration compared with the conditions in similarly treated but neonatally olive oil injected females; for both groups the concentrations decreased to the same and very low level after treatment with bromocriptine. The results suggest that DES treatment of neonatal mice enhances the capacity of the pituitary to release prolactin in response to estrogen in later life.

Animals↗
PubMed1980

Reduced natural killer activity in female mice after neonatal exposure to diethylstilbestrol.

Treatment of neonatal female mice with DES markedly reduced the activity of NK cells in adult mice. This finding was most evident in C57BL/6 and BALB/c strains, but was also found in outbred NMRI mice. The mechanisms behind the reduced NK activity was further analyzed. No evidence of DES-induced cellular or humoral suppressors of natural killing could be detected. Pregnancy was found to be without effects on NK. Poly I:C augmented the NK activity in control females but even very high doses of Poly I:C failed to increase the level of NK activity in neonatally DES-treated animals. The lack of response to boosting with Poly I:C was not due to alterations in kinetics of NK induction.

Aging↗
PubMed1980

Permanent inhibition of capping of spleen lymphocytes from neonatally oestrogen-treated female mice.

Female mice of the NMRI strain were injected with 5 microgram diethylstilboestrol (DES) or oestradiol-17 beta for the first 5 days after birth. Controls were given olive oil only. At the age of 4-6 months, the spleen lymphocyte population from the DES females had about half the percentage of cells undergoing capping after exposure to concanavalin A (Con A) as controls. The results from the oestradiol-injected females varied. After treatment of lymphocytes from DES females with colchicine, the percentage cells capping was as in control females. Binding studies did not reveal any difference in Con A receptor affinity or receptor number between DES females and controls.

Animals↗