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Biomedical subjects

E Saksela

Publications and source records attributed to E Saksela.

At least 73 records · Page 4Linked to original sources
PubMed1987

Increased number of functionally defective large granular lymphocytes in lymphoma patients.

50 untreated patients with either Hodgkin's disease or non-Hodgkin lymphoma were studied for natural killer (NK) activity on the single cell level. The non-Hodgkin lymphoma patients had a significantly higher proportion of large granular lymphocytes-cells mediating the natural cell mediated cytotoxicity in humans-among peripheral blood lymphocytes. Yet, the single cell assay in agarose and the standard 51Cr assay revealed a significantly decreased capacity to bind and lyse the K562 target cells. The recycling capacity was also found to be lower in the lymphoma patients' NK cells compared to the healthy controls.

Cytotoxicity Tests, Immunologic↗
PubMed1986

Bacterial activation of human natural killer cells. Characteristics of the activation process and identification of the effector cell.

We showed previously that contact of human peripheral blood lymphocytes with glutaraldehyde-fixed Salmonella bacteria augmented their cytotoxic capacity against NK-sensitive targets. We have now analyzed the characteristics of the activation and also identified the subsets of lymphocytes responding to bacterial contact. Blocking of protein synthesis with cyclohexamide totally abrogated bacterial induction of activated killing (AK), whereas inhibition of DNA synthesis with mitomycin C did not significantly affect the capacity of lymphocytes to respond to bacterial contact. Both the induction and the effector phase of AK were radioresistant. The AK cells exhibited efficient lytic activity, comparable to that induced by recombinant IL 2 (rIL 2), against NK-resistant targets (including both hematopoietic and solid tumor cell lines). All inducible cytotoxic activity was contained within the subset of lymphocytes expressing Leu-19 (NKH-1) antigen. Leu-19- lymphocytes exhibited no significant NK activity and could not be further stimulated by bacterial contact, rIL 2, or IFN-alpha. Within the Leu-19+ lymphocyte subset, two distinct cell types were present; CD3-, Leu-19+ NK cells and CD3+. Leu-19+ T cells. The CD3+, Leu-19+, T cells mediated low levels of non-MHC-restricted cytotoxicity against K562, but did not respond to bacterial contact, even though rIL 2 could augment their lytic activity slightly. However, the cytotoxic activity of CD3-, Leu-19+ NK cells was significantly augmented by bacterial contact. Within the CD3-, Leu-19+ NK cell population both CD16+ and CD16- cells responded to bacterial activation. The CD3-, CD16-, Leu-19+ cells constituted 1 to 4% of the Percoll-fractionated low buoyant density lymphocytes and accounted for the activation seen within the CD16- lymphocyte population. Thus bacterial stimulation of NK activity seems to be mediated for the most part via CD16+, Leu-19+ cells, and a minor overall contribution is mediated via CD3-, CD16-, Leu-19+ cells. No apparent involvement of T cells was seen in the lytic response of lymphocytes to bacterial contact.

Cell Line↗
PubMed1986

Identification and localization of urokinase-type plasminogen activator in human NK-cells.

We have studied the presence of plasminogen activators in large granular lymphocytes and other peripheral blood cells. After immunofluorescence staining with polyclonal antiserum against urokinase-type plasminogen activator, the majority of LGLs showed granular staining which was located in Golgiderived vesicles. LGLs were negative for tissue-type activator. The presence of only urokinase-type PA in LGLs was also confirmed by determining the molecular weight of the intracellular activator and by immunoblotting the antigen from solubilized cell preparations. Monocytes and granulocytes were more intensely stained with anti-u-PA than LGLs. In LGL/K562 cell conjugates the fluorescence was often located close to the contact area and the vesicular fluorescence polarized during conjugate formation. Inhibitors of PA and other serine proteinases are known to abolish NK-cell activity. We now show that they affect a later stage than programming for lysis in the cytotoxic action, suggesting a role for u-PA or other serine proteases in the lethal-hit stage of NK activity.

Antibody Specificity↗
PubMed1986

Bacterial induction of human activated lymphocyte killing and its inhibition by lipopolysaccharide (LPS).

Peripheral blood lymphocytes were incubated with glutaraldehyde-fixed Salmonella bacteria. This resulted in rapid activation of nonspecific cytotoxic potential of the lymphocytes. Both originally noncytotoxic, high-density Percoll-fractionated cells, and cytotoxic natural killer (NK) cell-enriched low-density cells were activated. The induction of originally noncytotoxic cells into activated killer (AK) cells was apparently independent of interferon (IFN), whereas the activation of the NK cell-enriched fractions also involved IFN production. Neither the AK nor NK activity were associated with significant bactericidal activity. The IFN-independent induction of AK activity was not dependent on the O-antigenic polysaccharide part of the lipopolysaccharide (LPS) on the bacterial cell surface, because both smooth (S) strains with differing O-antigenic structures (S-4,12 and S-6,7) and a rough (Re) strain without O-antigen were effective inducers. Isolated LPS, and especially alkali-hydrolyzed (O-deacylated, detoxified) LPS (ALPS) interfered with the induction of cytotoxicity. At concentrations of 10 to 30 micrograms/ml, ALPS totally inhibited the induction of AK activity without affecting the endogenous NK activity. Thus contact with bacteria can lead to the emergence of AK cells, and a bacterial product can effectively block this activation. These phenomena stress the complexity of interactions with host defenses that can take place during bacterial infection.

Antigens, Bacterial↗
PubMed1986

NK-9, a distinct sialylated antigen of the T200 family.

The nature and properties of antigens detected by a novel monoclonal antibody, NK-9, were studied. The NK-9 antigens had apparent molecular masses of 190, 200 and 220 kDa and were sensitive to neuraminidase and sodium metaperiodate treatments, which destroy the sialic acid residues of the cell surface glycoproteins. Trypsin treatment also removed the NK-9 reactivity, but the antigens were restored within a few hours thereafter. Tunicamycin, which inhibits the N-linked glycosylation after neuraminidase treatment, had no effect on the reappearance of the NK-9 positivity. Neither did endoglycosidase F, which removes the N-linked sugars, abolish the NK-9 antigenicity. Monensin, which blocks the cellular secretion, inhibited the restoration of the antigens, and monensin block also without preceding treatment with neuraminidase led to the disappearance of NK-9 reactivity, suggesting possible recycling molecules as carriers of the NK-9 detected epitopes. The NK-9 antigens appear to belong to the T200 antigen family, but are distinct from the antigens reactive with the available anti-T200 antibodies anti-LC, T29/33 and HLe-1, based on their different cell type distribution and absence of cross-reactivity in sequential immunoprecipitations.

Antibodies, Monoclonal↗
PubMed1985

Mr 75,000 protein, a tumor marker in renal adenocarcinoma, reacting with antibodies to a synthetic peptide based on a cloned human endogenous retroviral nucleotide sequence.

Using a rabbit antiserum to a synthetic undecapeptide deduced from a cloned human retroviral gag-gene-related DNA sequence, we found a specific immunohistochemical reaction in all of 42 tested renal cell adenocarcinomas (RCC), while none of 17 similarly tested Wilms' tumors and 65 carcinomas at other sites were positive. The RCC included two cases that presented with distant metastases. It had not been possible to establish the origin of these until immunohistochemical staining revealed this typical reaction. Subsequent renal angiography disclosed the primary. In immunoblotting the antiserum detected an Mr 75,000 protein in RCC tissue, and this reaction was blocked by the undecapeptide. The usefulness of this protein as a tumor marker for RCC is discussed.

Adenocarcinoma↗
PubMed1985

Common precursor pool marker for allospecific (CTL) and nonspecific (NK and activated) cytotoxic cells in the bone marrow.

A recently described monoclonal mouse IgG1 antibody, NK-9, reacts with practically all peripheral blood large granular lymphocytes (LGL). It also detects a population of non-LGL lymphoid cells that harbors precursor cells for both nonspecific activated killer (AK) and allospecific killer cells. In the bone marrow, the NK-9-positive population represented 9% of all nucleated cells, which was 40% of all lymphoid cells. This population was initially noncytotoxic, but when appropriately stimulated the NK-9-positive cells gave rise to AK and allospecific cytotoxic cells, whereas no such activity could be generated from the NK-9-negative cells. When the NK-9-positive cells were cultured with high concentrations of T cell growth factor, the results were cultures consisting of over 80% cells with LGL morphology and exhibiting effective cytotoxicity against K562 targets. It is concluded that the precursor cells for various modes of nonspecific and antigen-specific cytotoxicity are related and appear to be harbored in the NK-9-positive pool in the bone marrow.

Antibodies, Monoclonal↗
PubMed1984

A prospective, randomized, national trial for treatment of ovarian cancer: the role of chemotherapy and external irradiation.

A prospective, randomized, national trial for comparing the effects of cytotoxic agents and radiotherapy on survival in primary epithelial ovarian cancer stages I-IV was carried out in 363 patients. After laparotomy, the patients were staged according to disease spread and randomized into treatment groups within each stage. The single or combined cytotoxic agents used were: cyclophosphamide (C) and vincristine (V); 5-fluorouracil (F) and dactinomycin (D) and V; treosulfan (T); and CF. In stages I, II and III there was one treatment group receiving external irradiation; in stage IV only different cytostatics were used. It was found that, in stage I, surgery alone was superior to surgery +CV or surgery + irradiation. In stage II disease, no differences in survival between treatment groups receiving pelvic irradiation or FDV, and in stage III between whole abdomen + pelvic irradiation or CV or FDV were found. In stage IV, FDV, T and CF were of similar, poor efficacy. The authors conclude that in stage I pelvic irradiation or combined chemotherapy do not improve survival. In advanced disease, chemotherapy may be better tolerated and thus preferable to whole abdomen irradiation; the combination of more modern cancer drugs with the ones used in this study is probably likely to improve the treatment results.

Abdomen↗
PubMed1984

A shared antigenic specificity of human large granular lymphocytes and precursors of NK-like and allospecific cytotoxic effector cells.

We describe here a new monoclonal IgG1 antibody, NK-9, which recognizes practically all large granular lymphocytes (LGL), the mediators of human NK activity. This antibody also reacts with an originally noncytotoxic, non-LGL lymphocyte population that contains precursors of the inducible NK-like and allospecific cytotoxicity in the blood. The NK-like effectors are also NK-9+. The results thus suggest a close precursor relationship of endogenous NK cells, NK-like cells, and allospecific CTL in the blood. NK-9 antibody does not crossreact with B cells, monocytes, or granulocytes or with any of a large panel of cultured cell lines tested, including T and B cell as well as null cell lymphoma-leukemia lines. It does not inhibit the functional properties of the positive cells. The antigens for NK-9 antibody on the cell surface have m.w. of 190, 200, and 220 kD, and at least the former two appear to be glycosylated. The non-LGL, noncytotoxic NK-9+ cells contain only the 190 kD antigen, but the other two appear concomitantly with the induced NK-like cytotoxic activity on the cells. The NK-9-detected antigens are retained after formaline fixation, and NK-9 antibody can thus be used to stain normal formaline-fixed, paraffin-embedded histologic sections.

Animals↗
PubMed1983

Suppressor cells of the human NK activity: characterization of the cells and mechanism of action.

The surface marker characteristics and mechanism of action of small- to medium-sized NK suppressor lymphocytes, which can be found in both umbilical cord blood and adult peripheral blood, have been studied. Evidence suggestive of T-cell origin of the lymphocytes consisted of E-rosette formation, reactivity with OKT3 monoclonal antibody, and dot-like acid alpha-naphthyl acetate esterase (ANAE) staining pattern typical of T cells. Furthermore, no reactivity was seen with OKT6 and OKM1 monoclonal antibodies and the presence of intracytoplasmic immunoglobulin was excluded by indirect immunofluorescence microscopy, making the involvement of monocytes, B cells, and thymocytes less likely. As regards the mechanism of action, the role of prostaglandins was unlikely since indomethacin had no effect on the level of suppression. The role of soluble mediators was further examined by blocking cell secretion with monensin. In these experiments monensin treatment of the suppressor cells did not unwind suppression, suggesting that mechanisms other than secretion of suppressive factors were operative. The importance of cell-to-cell contact was demonstrated by the following observations: (i) A short contact of effector lymphocytes with suppressor lymphocytes, followed by their physical separation, resulted in decreased cytotoxic activity of the effector cells. (ii) Suppression could be mediated through Nuclepore filters, which allowed cell processes to pass through the filter, but not through filters which did not allow cell-to-cell contact. The suppressor cells were resistant to irradiation (2500 rad) and treatment with dexamethasone and puromycin. Viable cells were not needed, since paraformaldehyde-fixed suppressor cells could also mediate inhibition of K562 killing.

Antibodies, Monoclonal↗
PubMed1983

Vaginal polyps with pseudosarcomatous features. A clinicopathologic study of seven cases.

Seven cases of vaginal polyps with atypical stromal cells were investigated. Three of the cases were classified as vaginal rhabdomyoma and four as fibroepithelial polyps with atypical stromal cells. All of the patients were adult women with minor or no symptoms. None of the tumor recurred or metastasized. The recognition of the vaginal polyps with bizarre stromal cells is important in order to avoid misdiagnosis of sarcoma, particularly botryoid rhabdomyosarcoma.

Adolescent↗
PubMed1983

Are "natural killer" cells involved in allograft rejection?

"Natural killer" (NK) effector cells and large granular lymphocytes (LGL) are found inside rat renal allografts during rejection. Their appearance in situ precedes the appearance of cytotoxic T lymphocytes, and concomitantly with their influx in the allograft, the NK activity and the LGL are depleted from the recipient spleen. This suggests that the NK effector cells and the LGL are involved in allograft rejection, although their role(s) among the other in situ inflammatory effector pathways remains to be clarified.

Animals↗
PubMed1983

Non-specific binding of mouse immunoglobulins by swollen-bodied astrocytes--a potential source of confusion in human brain immunohistochemistry.

All classes of non-immune mouse immunoglobulins bind non-specifically to the cytoplasm of modified astroglial cells, swollen-bodied astrocytes, when applied to paraffin or frozen sections of human brain tumors and various reactive states. The binding could be inhibited by preincubation with normal human serum, and a proportion of the cells, which reacted with mouse immunoglobulins, showed spontaneous presence of various classes of human immunoglobulins. The Fc part of the immunoglobulins was involved in the binding, since preincubation of mouse immunoglobulins with protein A effectively inhibited the binding and the F(ab)2 fragments of mouse immunoglobulins showed no affinity to modified astroglial cells. The non-specific binding reported here effectively precludes the use of whole mouse immunoglobulins in the immunohistochemistry of human brain pathology.

Animals↗
PubMed1983

Suppressor cells of natural killer activity in normal and tumor-bearing individuals.

Suppressor cells of the human natural killer activity were found in normal peripheral blood and in the blood of patients with untreated primary carcinomas. When lymphocytes from healthy donors were fractionated by Percoll density gradient centrifugation, small lymphocytic, high-density cells inhibited K562 killing in 9/55 consecutively tested cases, and lymphocytes from tumor patients in 1/25 consecutively tested cases. Further fractionation of the suppressor cells was achieved by EA rosetting, since strong suppressor cell activity was seen in the population of cells forming EA rosettes with antibody-coated erythrocytes, whereas the nonrosette-forming cells did not generally suppress. Out of the 33 further fractionated samples from healthy donors, 20 rosette-forming lymphocytic cell fractions exerted strong suppression and out of the 7 samples from tumor patients 2 exerted suppression after EA rosetting. The increase in suppression after EA rosetting was partly due to enrichment of suppressor cells, and partly due to activation of FcR-positive suppressor cells after exposure to immune complexes. The involvement of soluble immune complexes, possibly retained on the suppressor cell surface, was ruled out by the following criteria (i) trypsin and pronase treatment of suppressor cells did not inhibit suppression, (ii) protein A had no effect on the level suppression, and (iii) suppression was also seen with cells which had not been exposed to immune complexes.

Adult↗
PubMed1983

Malignant mixed Müllerian tumor of the fallopian tube: report of a case with 5-year survival.

The literature reveals a total of only 25 cases of malignant mixed Müllerian tumor of the fallopian tube. Another case is presented; the patient is well and without evidence of disease more than 5 years after the operative treatment. She also received postoperatively adjuvant cytostatic treatment with cyclophosphamide, vincristine, adriamycin, and external radiation therapy. An aggressive mode of treatment is recommended in this rare disease due to the usually very poor prognosis.

Aged↗
PubMed1983

Expression of intermediate filaments in ovarian and uterine tumors.

We studied the expression of cytoskeletal intermediate filaments in different types of ovarian and uterine sarcomas and carcinomas. In both uterine and ovarian leiomyosarcomas, in endometrial stromal sarcomas, and also in ovarian sarcomas, most tumor cells appeared to be positive for desmin, the muscle type of intermediate filament protein. In most of the tumors, vimentin was present only in some neoplastic cells and in the vascular endothelia. Interestingly, both uterine and ovarian malignant mixed mesodermal tumors appeared to express several types of intermediate filaments, most of the stromal cells being positive for vimentin or desmin, and the epithelial component expressing keratin. The results show that most of the sarcomatous tumors of the ovary and uterus express mainly muscle type of intermediate filament protein. The results also demonstrate the ability of cells of mesodermal origin to express epithelial cytoskeleton markers--cytokeratins.

Adenocarcinoma↗