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Biomedical subjects

W L Olszewski

Publications and source records attributed to W L Olszewski.

At least 163 records · Page 9Linked to original sources

Influence of operative trauma on circulating blood mononuclear cells: analysis using monoclonal antibodies.

The influence of operative trauma on the quantity and proportion of cooperating mononuclear cells in peripheral blood of patients with stage 0 uterine cancer who underwent hysterectomy was studied using monoclonal antibodies. The percentage of OKM1+ cells (monocytes) had increased on day 1 by 12.4%, on day 3 by 24.8%, and had returned to normal by day 7. The percentage of large OKIa1+ cells (expressing Ia antigen) on day 1 was increased by 186.9%, while on day 3 it had returned to a normal level. There was a decrease on day 1 of the number and percentage of OKT3+ cells (all T lymphocytes) by 17.4%, OKT4+ cells (helper/inducer cells) by 27.9%, OKT8+ cells (suppressor/cytotoxic cells) by 24.6%, and small OKIa1+ cells by 49.4%. The number and percentage of T lymphocytes remained below the preoperative level throughout the observation period. However, the number of helper cells had increased significantly on day 5, while suppressor cells remained below the preoperative level during the entire observation period. The rising ratio of OKT4+/OKT8+ cells reflected the kinetics of recovery of the helper over the suppressor cell population.

Adult↗

Natural killer (NK) cell cytotoxicity in athymic (nude) rats.

The in vitro and in vivo natural killer (NK) cell activity of congenitally athymic, nude (ATH) rats and of normal, euthymic (EUTH) rats was compared. We found: a) a higher level of in vitro NK cell activity in blood, spleen and lymph nodes of ATH rats compared with their heterozygous littermates, b) in the spleen the number of NK lytic units per organ was not higher in ATH compared with EUTH whereas it was significantly higher in lymph nodes, c) a lack of age-dependence of in vitro NK cell activity tested in culture with heat inactivated fetal calf serum, d) a higher rate of in vivo elimination of target tumor cells in 4-week ATH rats compared with EUTH rats, e) an age-dependent decrease in the rate of in vivo target cell elimination in both groups, and finally, f) an age-dependent increase in the inhibitory effect of autologous serum on NK cell activity in vitro in both groups. These findings show that the blood and lymphoid organs of athymic rats contain a substantially higher proportion of NK cells, active both in vitro and in vivo against K562 tumor cells, than their euthymic littermates. In the spleen this increased proportion can be attributed to the lack of T cells, whereas in the ATH rat lymph nodes there is an absolute increase in NK cell activity, and that the decrease of cytotoxicity in vivo with age reflects the increasing inhibitory properties of autologous serum both in nude and in normal rats.

Animals↗

Immunological characteristics of cells entering the liver with portal blood.

The mononuclear cell populations were characterized phenotypically and functionally in the splenic, mesenteric, portal, sinusoidal, and hepatic venous blood. We found higher concentrations of mononuclear cells in splenic than mesenteric and portal blood; splenic blood contained high numbers of cells with Fc, C3b receptors and surface immunoglobulin and OX8+ (cytotoxic/suppressor) cells. Liver sinusoidal blood was enriched, compared with inflowing portal blood, in cells with Fc, C3b receptors and surface immunoglobulin, OX+8 cells, and natural killer and killer cells. These findings indicate that the spleen may be the main source of migrating streams of cells to the liver and that cytotoxic subsets of these cells are retained in that organ.

Animals↗

The effect of surgery and chemotherapy on blood NK cell activity in patients with ovarian cancer.

The cytotoxic activity of NK cells in peripheral blood was studied in 15 patients with ovarian cancer Stage III and IV before and after surgery and ten-week intramuscular therapy with thiotepa. An evident decrease in NK activity was found 24 hours after surgery, with a slow return toward normal values within 7-9 days. No differences between patients with explorative laparotomy and with extirpation of the tumor were observed. The mechanism of the decreased NK cytotoxicity remains unknown but there was a concomitant reduction in the number of blood mononuclears. A second drop in NK activity occurred after chemotherapy. It was most likely due to the drug bone marrow depression. No evident correlation between the reduced NK activity and advancement of the disease could be found.

Adult↗

Rat liver contains a distinct blood-borne population of NK cells resistant to anti-asialo-GM1 antiserum.

A high level of anti-tumoral (NK) cytotoxicity was observed in the mononuclear population washed out from the liver microvasculature in rat. The level of cytotoxicity against K562 and YAC1 cells, percentage of large granular lymphocytes (LGL) and of OX8+ cells was significantly higher than in the inflowing portal and also caval blood. A low concentration of adherent, phagocytic and OX6+(Ia) cells and a higher level of cytotoxicity after removal of adherent cells ruled out the possibility of liver macrophages to be responsible for the cytotoxicity. Surprisingly, the liver-sequestered NK population turned to be resistant to anti-asialo-GM1 antiserum. Thus, liver microvasculature contains a significant number of cells with characteristics of NK cells which constitute a functionally distinct NK population.

Animals↗

Suppressor cell activity in peripheral blood in cancer patients after surgery.

The influence of operative trauma on the responsiveness of PBM to PHA and Con A and the level of Con A-induced suppressor cell (Con A-SC) activity toward autologous responder cells (RC) were examined in patients with stage 0 uterine cancer after hysterectomy. The operation brought about a decrease on the second post-operative day in the responsiveness of PBM to various concentrations of PHA by 19.2-28.8% and to Con A by 31.2-41.8%, concomitantly with a decline in Con A-SC activity from 43.7 to 22.0%. When the Con A-SC were tested against RC obtained from blood samples drawn prior to surgery and stored at -196 degrees C, an increase in the post-operative SC activity from 41.6 to 52.2% was observed which might indicate a post-operative stimulation of SC. On the other hand, when Con A-SC were raised from PBM drawn before surgery and tested against RC obtained post-operatively, they displayed a decreasing suppressive activity from 27.2 to 2.7%. This might be due to the pre- and post-operative stimulation of RC. The observed changes were most likely caused by a transient decrease in the number of blood T lymphocytes, altered proportions of blood T cells to other PBM cells and probably a non-specific stimulation of autologous cells responding in the suppressor cell activity assay.

Adult↗

Hyperacute rejection of xenografts. I. Differences in affinity to ConA--Sepharose of IgG--fraction of the affluent and effluent blood.

The immunoglobulin fraction from affluent and effluent sera from the rabbit liver transplanted to a dog partially purified on ion exchange DEAE--Sephadox A-50 was chromatographed on ConA-Sepharose. The picture of SDS polyacrylamide slab gel electrophoresis (PAGE) showed in the xenograft serum a considerably higher intensity of bands corresponding to the mobility of heavy and light IgG chains. This suggested the presence of glycoproteins coupled to IgG. Immunoelectrophoresis proved occurrence in the transplant serum of at least six additional components precipitating with whole anti-dog serum. These components could be either glycoprotein antigens or complement components, free or bound to IgG subclasses.

Animals↗

Hyperacute rejection of xenografts. II. Isolation of individual components of the graft effluent serum.

Separation of glycoprotein components from Con A-Sepharose in acid solution gave an electrophoretic picture of transplant serum containing a "double band" which was not found on any electrophoresis of fractions eluted from Con A-Sepharose at pH 7.4. This band corresponded with mobility to proteins of molecular weight higher than heavy IgG chains. We assume that at pH 3 the observed picture of the new protein may be a glycoprotein antigen dissociated from the immunological complex. Immunophoresis of the transplant serum fraction confirmed our assumption that at pH 3 there appeared a new component absent at pH 7.4. Our attempts at separating this component on Sephadex G-150 were unsuccessful.

Animals↗

Synergistic effects of ATS and passive and active enhancement on heart and skin allografts in rats.

The effect of a combination of specific and non-specific immunosuppression on survival of heart and skin allografts in parental strain rats differing across the major histocompatibility locus was investigated. Pretreatment of the recipient with donor specific antigen and anti-donor alloantiserum prolonged the survival of heart grafts but not skin grafts. The use of antilymphocyte serum prolonged skin graft survival but not heart graft survival. However, when ATS was combined with donor specific immunosuppression, both heart and skin graft survival were prolonged dramatically. It is suggested that these treatment modalities affect differentially various aspects of the immune responses.

Animals↗

High spontaneous and mitogen-induced activity of mononuclear cells in lymph draining normal human skin.

Lymphocytes in afferent lymph draining skin are derived from populations selected at the capillary level to enter the tissue space and which migrate spontaneously through the tissue to the initial lymphatics. These cells reveal a high spontaneous transformation rate in a 72 h culture. The mean 3H TdR incorporation was in a 24 h culture 2 times and in a 72 h culture 5 times higher than that of the peripheral blood mononuclear cells of the same subjects. The lymph cells responded significantly stronger to low concentrations of PHA, ConA and PWM than the blood cells. Also, the peak response of lymph cells was apparent at lower concentrations of mitogen in culture than of blood cells. The lymph cell population revealing a high spontaneous transformation rate was found to be the OKT4 enriched subset (induced/helper). The findings of a high spontaneous activation of lymphocytes which trafficked through the normal skin and defining this highly reactive subset as an OKT4-positive and strongly responsive to mitogens, reflect the in vivo immune events in the normal skin.

Adolescent↗

Cells in lymph draining normal human skin-monoclonal antibody analysis.

The immune cells which migrate into the human skin from the blood and subsequently leave it via lymph vessels play an important role in immune processes. We made use of the monoclonal antibodies, characterizing cell populations which migrate into the normal skin and which having traversed the tissue, could be recovered from the afferent lymph vessels. The percentage of OKM1+ cells (monocytes/macrophages, null cells) in lymph was low (8.9 +/- 1.6%) when compared to that of blood (16.5 +/- 4.6%) (p less than 0.05). The OKM1 antibody labeled only 40% of the large macrophage-like lymph cells. The percentage of OKT3+ (T cells) in lymph was higher (75.4 +/- 4.0%) than in blood (54.0 +/- 4.5%) (p less than 0.05) as was that of the OKT4+ (inducer/helper) subset (41.5 +/- 9.5 and 33.3 +/- 4.8%, p less than 0.05), while cells of the OKT8+ (suppressor/cytotoxic) subset were found to be less numerous in lymph than in blood. (18.4 +/- 6.2% and 20.3 +/- 4.9%, p less than 0.05). The OKI a1+ cell population consisted of large veiled macrophage-like cells and only very few small cells. Around 60% of the large mononuclear cells present in lymph reacted with OKT6 antibody specific for cortical thymocytes. The finding of high proportions of T cells, cells bearing la-like antigens, and a high inducer/suppressor ratio in normal prenodal lymph reflects the intensity of "physiological" immune processes in the normal skin.

Adolescent↗

C1 inactivator and C3b inactivator in peripheral lymph of normal men.

The concentrations of C1 inactivator and C3b inactivator were measured in the peripheral lymph of leg of normal men and compared with the concentrations in serum. Both inactivators were found in lymph, however, in concentrations lower than in serum (lymph/serum ratio for C1INA 0.236, for C3bINA 0.238). The levels of C1INA proteins in lymph were higher than of C1q and C1s (p less than 0.05), and of C3bINA higher or equal to those of C3 and C3PA. This may indicate, that the relatively high concentrations of both inactivators in the extravascular space, as compared with complement component proteins, can play a role in the control of activation process of complement in the interstitium and also explain to some extent the observed low hemolytic activity of lymph C1 and C3.

Adolescent↗