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J Tarkkanen

Publications and source records attributed to J Tarkkanen.

At least 19 recordsLinked to original sources
PubMed1992

Involvement of beta 2-integrins in the migration of human natural killer cells.

Human large granular lymphocytes with the NK cell phenotype (CD16+ or CD56+CD3-) were greatly enriched among the cells which migrated spontaneously through untreated or albumin-coated, 3-microns pore size polycarbonate filters for 1 to 8 h. Three days of rIL-2 treatment (300 IU/ml) and 3 to 5 wk of rIL-2 treatment (100 IU/ml) generated a 2.7 +/- 0.9-fold and 5.6 +/- 0.8-fold increase in cell migration, respectively. The adhesion and subsequent migration of freshly isolated NK cells was mainly mediated by CD11b/CD18, because migration could be inhibited by 80 +/- 8% anti-CD11b (Mac-1) antibodies but not with antibodies against CD11a (LFA-1) or CD11c (p150,95), the other alpha-chains of the beta 2-integrins. After rIL-2 activation, however, CD11a/CD18 was the major receptor utilized in migration, inasmuch as anti-CD11a antibody caused a 69 +/- 8% reduction in the number of migrated cells. Anti-CD11b antibody decreased migration by 43 +/- 12%, and together these antibodies inhibited migration by 82 +/- 7%. Anti-CD11a alone did not have any effect on adhesion, but CD11a/CD18 cooperated in the adhesion because anti-CD11b decreased adhesion by 40 +/- 11% and together these antibodies inhibited adhesion by 74 +/- 6%. The ability of large granular lymphocytes to rapidly utilize beta 2-integrins and unidentified ubiquitous ligands for binding and migration may be significant for their capacity to function in the first line of immune defense under highly variable conditions.

Antibodies, Monoclonal↗
PubMed1992

Migration of recombinant IL-2-activated T and natural killer cells in the intercellular space of human H-2 glioma spheroids in vitro. A study on adhesion molecules involved.

The migration of rIL-2-activated T and NK cells into the intercellular space of glioma tissue was studied using multicellular spheroids grown from the human H-2 glioblastoma cell line as targets. Lymphocytes of all analyzed subtypes migrated into the spheroids, but CD56+ cells were particularly migratory. Lymphocytes and the H-2 tissue expressed adhesion molecule subunits for the following potential cell-cell or cell-matrix interactions: alpha 3 beta 1 (VLA-3) to fibronectin, laminin, and collagen; alpha 4 beta 1 (VLA-4) and alpha 5 beta 1 (VLA-5) to fibronectin; alpha 6 beta 1 (VLA-6) to laminin; alpha 4 beta 1 to VCAM-1; alpha L beta 2 (Leu-CAMa/LFA-1) to CD54 (ICAM-1); CD44 to fibronectin, collagen, laminin, hyaluronate; CD2 to CD58 (LFA-3); and CD56 (N-CAM) to CD56. In the H-2 tissue, CD54 and VCAM-1 were expressed as a gradient. The expression of CD54 was weak in the peripheral zone and the expression was stronger in the quiescent deeper zone, whereas the distribution of VCAM-1 showed an inversed pattern. The low expression of CD54 was up-regulated along the frontier of migrating lymphocytes. The migration was almost totally prevented by the anti-CD18 (beta 2) mAb IB4 and TS1/18, and also strongly inhibited by the anti-CD54 mAb LB-2. Instead, mAb known to inhibit the binding of beta 1 integrins to fibronectin were not significantly inhibitory. However, a combination of the GPEILDVPST and GRGDS peptides, which compete for the binding of alpha 4 beta 1 and alpha 5 beta 1 to fibronectin and may also affect other adhesion systems, partially prevented migration.

Amino Acid Sequence↗
PubMed1991

Potentiation of human natural killer cell cytotoxicity by Salmonella bacteria is an interferon- and interleukin-2-independent process that utilizes CD2 and CD18 structures in the effector phase.

Incubation of large granular lymphocytes (LGL) with glutaraldehyde-fixed bacteria stimulated in the supernatant the production of interferon (IFN), which proved to be mainly IFN-gamma. Even though IFN-gamma was produced upon exposure of LGL to bacteria, anti-IFN-gamma antibodies failed to interfere with induction of cytotoxicity by bacterial contact. Anti-IFN-gamma receptor antibodies had no effect on the induction of activated killing by bacterial contact either. We also tested the effect of anti-IFN-alpha antibody, but it failed to interfere with induction of cytotoxicity by bacterial contact. No interleukin-2 (IL-2) was detected in the culture supernatant of bacterially activated LGL by the mouse HT2 cell assay, nor did we detect any IL-2 mRNA in bacterially activated LGL by Northern RNA blot assay. Neutralizing anti-IL-2 antiserum had no effect on the induction of activated killing by bacterial contact, and recombinant IL-4 did not interfere with the induction of activated killing. We then studied the membrane structures involved in bacterially activated killing. Anti-CD18 monoclonal antibody did not interfere with the induction phase of bacterially activated killing. However, both anti-CD18 and anti-CD2 antibodies inhibited the effector phase of bacterially activated killing. The effector pathways utilized by activated LGL depended on the mode of activation in that even though bacterially activated LGL were sometimes blocked by anti-CD2 monoclonal antibody, recombinant-IL-2-stimulated LGL were not. In conclusion, our present results suggest that there may be mediators other than exogenously secreted IFNs and IL-2 which are responsible for the induction of activated killing after bacterial contact. CD18 and CD2 structures were shown to be involved in the effector phase of bacterially activated killing.

Antibodies, Monoclonal↗
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

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↗
PubMed1985

Comparison of diazepam and midazolam for sedation during local anaesthesia for bronchoscopy.

Bronchoscopy was performed in 76 outpatients using local anaesthesia plus diazepam 0.2 mg kg-1 i.v. or midazolam 0.05 or 0.1 mg kg-1 i.v. Patient co-operation and ease of bronchoscopy were good in all patients. Two hours after injection, 67% (diazepam 0.2 mg kg-1), 36% (midazolam 0.05 mg kg-1) and 75% (midazolam 0.1 mg kg-1) of the patients failed to recall the insertion of the bronchoscope. Similarly, when asked on the following day, only 22%, 52% and 8%, respectively, of the patients remembered bronchoscopy. Two hours after sedation, the patients' performances in three psychomotor tests were similar to those measured before sedation in each group, but the patients' ability to stand steadily and walk along a straight line reverted to normal significantly (P less than 0.05) more slowly in patients receiving midazolam 0.1 mg kg-1 than in the patients given diazepam. The results suggest that midazolam offers no advantage over diazepam in terms of speed of recovery of psychomotor function, when doses of similar potency are given for bronchoscopy.

Aged↗
PubMed1984

Adjuvant postoperative radiotherapy, chemotherapy, and immunotherapy in stage III breast cancer.

One hundred twenty pathologically confirmed operable Stage III (T3N0-2) breast cancer patients were randomized to receive either postoperative radiotherapy or chemotherapy, or a combination of these, with or without levamisole immunotherapy. Radiotherapy was given to regional lymph node areas and chest wall. Chemotherapy consisted of 6 cycles of Adriamycin (doxorubicin) (45 mg/m2), vincristine (1.2 mg/m2) intravenously, and cyclophosphamide (200 mg/m2 for 5 days) perorally every 4 weeks. Peroral levamisole, 150 mg a day, 2 days weekly, was given as an immunotherapy. The 3-year results are described in this article. The effect of levamisole on the prognosis cannot be evaluated yet because of the short follow-up period. The disease-free survival was almost equal in each patient group, however, some benefit was achieved by levamisole (a shift of disease-free survival from 12 to 18 months). The patients receiving radiotherapy alone had the poorest prognosis: 68% had a recurrent tumor, and 57% were alive. In the chemotherapy group, the figures were 53% and 72%, respectively. Patients who received a combined treatment had the best prognosis: 13% had a recurrent tumor, and 90% survived 3 years. There was a statistically significant difference in the recurrence rate between any single therapy and the combined treatment (radiotherapy to combined treatment, P less than 0.001, chemotherapy to combined treatment, P less than or equal to 0.01 chi-square test). In overall survival, a statistically significant difference was reached between radiotherapy and combination treatment groups (P less than 0.01, chi-square test). Radiotherapy gave a good local control of the tumor, and chemotherapy decreased the number of metastases. The nonmetastatic axillary lymph node status and secondary amenorrhea or severe menstrual disturbances were of positive prognostic value. The side effects due to radiotherapy and chemotherapy were moderate and tolerable. The dose of Adriamycin had to be reduced only in four patients. All of the patients receiving chemotherapy had a transient total alopecia. Three of them had nonlethal arrhythmias, and one had skin rash. Levamisole was found very toxic with 9 cases of transient agranulocytosis, leading to the discontinuation of immunotherapy in 22 of 59 patients. Our results show that radiotherapy controls the tumor only locally and chemotherapy systematically, but the best patient-saving results are achieved with a combination of radiotherapy and chemotherapy. The disease-free and overall survival are statistically significant, and favor the combined therapy.

Adult↗
PubMed1984

Caldwell-Luc operation in the treatment of childhood bronchial asthma.

A follow-up study was carried out in 15 children with severe bronchial asthma. Chronic infection of the paranasal sinuses was connected with the unfavorable course of their bronchial asthma. As adenoidectomy and intranasal antrostomy had failed to cure the sinusitis, the Caldwell-Luc operation was performed at the age of 6-16 years. The follow-up examination was done 3-12 years after the radical operation of the maxillary sinuses. The majority of the patients had normal working capacity, and the need of medical treatment was reasonable. It is concluded that the Caldwell-Luc operation is indicated in children with severe bronchial asthma, when repeated respiratory infections are associated with asthmatic attacks and adenoidectomy and intranasal antrostomy have proved ineffective.

Adolescent↗
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

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

Interferon-induced autologous reactivity of human natural killer cells.

The reactivity of human natural killer (NK) cells against normal autologous target cells was studied. The following major observations were made: (i) non-stimulated NK cells did not lyse autologous target cells, although allogeneic cells were killed to some extent. However, treatment of effector cells with interferon (IFN) resulted in induction of autologous cytotoxicity, and both autologous and allogeneic fibroblast targets were efficiently killed without preference. This was demonstrated both with unfractionated lymphocytes and with effector cells highly enriched in large granular lymphocytes (LGL). (ii) NK cells bound to autologous cells as efficiently as to allogeneic cells. The cells binding to autologous cells were able to lyse K562 cells, demonstrating their NK nature. After stimulation with IFN autologous cells were also killed. (iii) The exemption from autologous cytotoxicity by the non-stimulated NK cells seemed to result from a block at a post-binding stage, and there did not appear to be any need for accessory cells in the induction of autologous reactivity by IFN treatment of the LGLs. The results thus point to important post-binding-stage regulatory mechanisms saving normal cells from the cytotoxic action of circulating NK cells and may help to understand the suggested role of NK cells in certain autoimmune diseases.

Fetus↗
PubMed1983

The effect of instrumentation with a telescope during bronchoscopy on arterial oxygen tension and acid-base balance.

The effect of instrumentation with a telescope during bronchoscopy on the arterial oxygen tension and acid-base status was studied in 17 unselected, anaesthetized patients using a ventilating technique based on Sanders' method (1). After ventilating the patients with a bronchoscope and a telescope in the trachea, in the left main bronchus or in the right main bronchus, the PaO2 value was always statistically significantly higher than after ventilating only with a bronchoscope. During the course of the bronchoscopy as well as after 1 h in the recovery room, the arterial acid-base status was within normal limits and the mean PaO2 value during bronchoscopy ranged from 175 to 240 mmHg (23.3-31.9 kPa) and was 138 mmHg (18.4 kPa) in the recovery room when the patients breathed about 35% oxygen in air. The present results suggest that instrumentation with a telescope during bronchoscopy ameliorates rather than impairs the ventilation and oxygenation of the patients.

Acid-Base Equilibrium↗
PubMed1983

Tigason (etretinate) in prevention of recurrence of superficial bladder tumors. A double-blind clinical trial.

The effect of Tigason (etretinate) in the prevention of the recurrence of superficial bladder tumors (Ta-T1, grade 0 papilloma and grade 1 and 2 carcinoma) was studied in 30 patients in a double-blind, placebo-controlled study. Before beginning treatment, the bladder was cleared from all visible tumors by electrocoagulation or TUR. The duration of treatment ranged from 10 to 26 months. The overall preventive effect was significantly better (p less than 0.01) in Tigason-treated patients than in patients given placebo. Tigason was more effective in preventing the recurrence of grade 1 and 2 carcinoma than placebo. On grade 0 papilloma this difference was not so marked. Side effects were common and disturbing at high doses (50 mg/day), but Tigason was well tolerated at the final maintenance dose (25 mg/day). The results obtained from this first clinical study with Tigason in the prevention of recurrence of superficial bladder tumors are promising.

Aged↗
PubMed1982

Umbilical-cord-blood-derived suppressor cells of the human natural killer cell activity are inhibited by interferon.

The natural killer (NK) activity of umbilical-cord-derived lymphocytes was studied. The general level of activity was lower than with adult lymphocytes against K-562 cells and fetal fibroblasts. The activity could be boosted by interferon pretreatment of effect or cells, fractionated with Percoll density gradient centrifugation, and the suppressive activity of different fractions was tested on highly enriched adult buffy-coat-derived NK cells. Allogeneic adult NK cell activity could be inhibited in 9 of 20 cases tested with small and medium-sized T lymphocytes (Percoll fractions 4-5) from the umbilical cord. The suppressive capacity was further enriched in fractions forming rosettes (RFC) with antibody-coated human erythrocytes (EA). Such EA-RFC of percoll fraction 4-5 from umbilical cord exerted a strong suppressive activity in each case tested. Pretreatment of EA-RFC with interferon regularly abolished the suppressive effect. We conclude that there are Fc-receptor-positive small/medium-sized T lymphocytes in the umbilical cord blood which can efficiency suppress the cytotoxic activity of NK cells and that the suppressive activity can be abolished by interferon pretreatment of the suppressor cells.

Adult↗
PubMed1978

Effect of age on amnesia and sedation induced by flunitrazepam during local anaesthesia for bronchoscopy.

Bronchoscopy was undertaken in 79 outpatients using local anaesthesia plus an i.v. injection of flunitrazepam 0.01 mg kg-1. The co-operation of the patients and the ease of bronchoscopy were good regardless of the age of the patient. There was an increase in amnesia for the bronchoscopy with increasing age, but the most distinct difference between different age groups was that the amnesic action of flunitrazepam was evident earlier and persisted longer in patients of more than 60 yr. Eye co-ordination and ability to stand steadily and walk on a line returned to normal more slowly in patients more than 60 than in those less than 60 yr, but no differences in recovery were noted between patients less than 40 and those of 40--59 yr, or between those 60--69 and those more than 70 yr.

Adult↗
PubMed1978

Comparison of diazepam and flunitrazepam for sedation during local anaesthesia for bronchoscopy.

Diazepam and flunitrazepam were compared as amnesic and sedative adjuncts to local anaesthesia for diagnostic bronchoscopy in 92 patients. After local anaesthesia of the pharynx, larynx and trachea with lignocaine, atropine plus diazepam of flunitrazepam was injected i.v. The co-operation of the patients and the technical circumstances under which the bronchoscopy was performed were good in each group. None of the treatments significantly modified arterial pressure or heart rate. Two hours after the injection, flunitrazepam 0.01 mg kg-1 more frequently caused amnesia for pictures shown to the patients during the first 15 min after injection (failure to recall 42--75%, and for bronchoscopy 67%), than did diazepam 0.125 mg kg-1 (failure to recall 21--67%; bronchoscopy 38%). Double doses of the drugs caused amnesic actions similar to those of flunitrazepam 0.01 mg kg-1. When failure to recall was assessed on the following day, 29% and 5% of the patients remembered bronchoscopy after flunitrazepam 0.01 and 0.02 mg kg-1 respectively; after diazepam 0.125 and 0.25 mg kg-1 the corresponding percentages was 59% and 30% (P less than 0.05% v. fluintrazepam). The ability to stand and walk on a stright line was similar after the smaller doses of both drugs, but after the larger doses recovery was slower after flunitrazepam. Psychomotor performance was still distinctly impaired 2 h after the injection of the larger doses.

Adult↗
PubMed1977

Influence of Caldwell-Luc operation on developing permanent teeth.

The influence of Caldwell-Luc operation on the permanent teeth of school children was studied in a material of 21 six to 14-year-old children, who had undergone, altogether, 30 Caldwell-Luc operations. Ten of the children had also undergone 23 endonasal antrostomies. The control material consisted of a class of 27 healthy school children, their mean age being 10.2 years. Total anesthesia was found in five teeth on the operated side and in one tooth on the non-operated side. Additionally, the operation had caused slight hypesthesia in part of the teeth, mostly in the first incisors. All sensory disturbances were caused by nerve lesion only, and no tooth had died as a result of the operation. The operation could not be shown to be conducive to caries. Correctly performed, Caldwell-Luc operation does not cause serious dental injuries in school children, and is indicated especially in chronic sinobronchitis when conservative methods of treatment fail.

Adolescent↗