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Biomedical subjects

H Wagner

Publications and source records attributed to H Wagner.

At least 541 records · Page 30Linked to original sources
PubMed1985

In vitro maturation of B cells in chronic lymphocytic leukemia. I. Synergistic action of phorbol ester and interleukin 2 in the induction of Tac antigen expression and interleukin 2 responsiveness in leukemic B cells.

Recent evidence indicates that interleukin 2 (IL 2), formerly thought to serve as growth factor exclusively for activated T cells, is directly involved in human B cell differentiation. We have investigated the role of IL 2 and IL 2 receptors (as defined by monoclonal anti-Tac antibody) in the phorbol ester-induced in vitro maturation of leukemic B cells from patients with chronic lymphocytic leukemia (CLL). Peripheral blood lymphocytes from B cells from CLL patients with high (greater than 10(5)/microliters) white blood cell counts were depleted of residual T lymphocytes and low-density cells (primarily macrophages) by consecutive steps of E rosetting, complement-mediated lysis of OKT3+ and OKT4+ cells, and Percoll density gradient centrifugation. No OKT3+ T cells were detectable in these cell populations before or after culture. When incubated for 3 days with phorbol ester plus recombinant human IL 2 (rIL 2), 12 to 57% of highly purified B cells from four of five tested patients expressed Tac antigen. Both phorbol ester and rIL 2 were required for maximal Tac antigen expression. Functional studies revealed that phorbol ester-activated (but not resting) CLL B cells responded to rIL 2 with [3H]thymidine incorporation and with enhanced secretion of IgM. Tac+ B cells were isolated in two cases on a fluorescence-activated cell sorter. In one patient, stimulation of Tac+ B cells with rIL 2 resulted in enhanced [3H]thymidine incorporation but no change in IgM secretion, as compared with Tac- B cells; in the second patient, stimulation of Tac+ B cells with rIL 2 did not result in [3H]thymidine uptake, but did result in significant IgM secretion. These findings indicate that certain leukemic B lymphocytes can be induced to express IL 2 receptors and respond to IL 2. The use of resting clonal B cell populations arrested at distinct stages of differentiation may help to better define the stage(s) at which IL 2 acts directly on B cells to induce proliferation and/or terminal differentiation.

Antibodies, Monoclonal↗
PubMed1985

[Esophageal carcinoma: surgery using transhiatal esophagectomy without thoracotomy].

During the period between 1982 and 1984, 25 patients with carcinoma of the esophagus underwent esophageal resection by the technique of blunt transhiatal esophagectomy without thoracotomy. The esophagus was replaced with stomach. The indications for blunt dissection of the esophagus are discussed and the operative technique is described. There was no postoperative mortality. Complications included pulmonary complications (19), anastomotic leak (9), left vocal cord paralysis (5) and stenosis of the cervical anastomosis (7). Postoperative hospitalization averaged 18 days. Following discharge from hospital patients are seen in follow-ups at 3-month intervals for 1 year, then at 6-month intervals. Quality of life is good. In the majority of patients with esophageal carcinoma, the goal of esophagectomy is palliation, not cure. Therefore, long-term prognosis of esophageal carcinoma is poor. Actual survival among the patients is 49% at 12 months, and mean survival 10.2 months. Transhiatal esophagectomy without thoracotomy is a safe procedure and far better tolerated by elderly and debilitated patients than a combined transthoracic and abdominal operation. We believe that this procedure is the treatment of choice for esophageal carcinoma at all levels.

Aged↗
PubMed1985

Developmentally controlled expression of IL 2 receptors and of sensitivity to IL 2 in a subset of embryonic thymocytes.

At various times of gestation murine fetal thymocytes were tested for IL 2 receptor (IL 2-R) and T cell differentiation antigen expression. The majority of 14 to 15 day fetal thymocytes were IL 2-R and Thy-1 antigen positive, yet negative for the Lyt and L3T4 marker. A subset of IL 2-R-positive fetal thymocytes could be induced by recombinant IL 2 to proliferate over at least 10 days. Growth of these proliferating cells could not be enhanced by syngeneic feeder cells nor suppressed by monoclonal anti-I-A or anti-I-E antibodies. No antigen-specific effector functions could be induced in the proliferating Thy-1, IL 2-R-positive cells. As a whole, the results suggest a developmentally controlled rather than antigen-induced expression of IL 2-R during embryogenesis of thymocytes.

Animals↗
PubMed1985

On the partial suppression of IL-2 receptor expression and the prevention of lectin-induced lymphoblast formation by cyclosporine A.

The effect of cyclosporine A (CyA) on the expression of the Tac-antigen (IL-2 receptor) on PHA-activated PBMNC was analysed by immunofluorescence. In the initial experiments we determined the number of Tac(+) cells, disregarding cell size; we found that CyA did not affect the number of cells expressing the Tac antigen after lectin stimulation (Fig. 1, Table 1). When we found that comparable numbers of Tac(+)-lymphocytes absorbed less IL-2 when grown in CyA as compared to solvent controls, we analysed in more detail the correlation between Tac-antigen expression and cell size of cell populations grown in CyA. It was found that CyA prevented a majority of PHA-activated PBMNC to undergo blastogenesis despite having expressed the IL-2 receptor. A minority of the cells, however, were refractory to the CyA-mediated suppression of blast formation. Studies analysing the Tac antigen expression semiquantitatively showed that CyA reduced the intensity of Tac antigen expression on cells of all sizes.

Cyclosporins↗
PubMed1985

[Rehabilitation of the physically handicapped--even today an ongoing task for orthopedics?].

Rehabilitation of disabled people has at all times been an essential element of orthopaedics. The great advances made in orthopaedic surgery over the last few decades have however not resulted in rehabilitative activity having become superfluous. On the contrary, better medical restoration provides a better starting base for vocational rehabilitation. Rehabilitation generally has better technical possibilities today than it used to, which contributes to its being more successful today. Most important of all has however been the progress entailed by a fundamental change in how rehabilitation is conceived: Today, we consider the disabled person a full and equal member of our society, whose integration in competitive employment we mean to foster to the greatest extent possible.

Adolescent↗
PubMed1985

[Immunostimulating action of polysaccharides (heteroglycans) from higher plants].

From the water or alcaline-water extracts of Echinacea purpurea (L.) Moench. and -angustifolia DC., Eupatorium cannabium L. and -perfoliatum L., Chamomilla recutita L. Rauscher, Calendula officinalis L., Baptisia tinctoria (L.) R. B., Achyrocline satureioides DC., Arnica montana L., Sabal serrulata Roem. et Schult., and Eleutherococcus (Acanthopanax) senticosus Maxim. polysaccharide fractions with molecular weights in the range of 25 000 to 500 000 and higher have been isolated, which, according to the granulocytes- and carbon clearance tests, showed significant immunostimulating activities. The isolated compounds belong to the group of watersoluble, acidic branched-chain heteroglycans. Their immunostimulating activity is compared and discussed with respect to other polysaccharides of biological activity.

Adjuvants, Immunologic↗
PubMed1985

Coding of light intensity and stimulus duration in the receptor potential of the isolated rabbit retina.

The receptor potential of the isolated rabbit retina was recorded between a microelectrode approximately 80 microns deep from the inner limiting membrane and a reference electrode at the receptor side. Amplitude and slope of the receptor potential and the area under it were measured as a function of increasing stimulus intensity and the amplitude and duration of the receptor potential as a function of stimulus duration. The amplitude depends on the intensity and duration of the stimulus. The slope is the single parameter which changes only with light intensity. The slope follows a power function with n = 0.36. The duration of rabbit receptor potential is linearly related to the duration of long stimuli (greater than 1 s for intensities tested).

Animals↗
PubMed1984

Presence of poly (ADP-ribose) polymerase and poly (ADP-ribose) glycohydrolase in the dinoflagellate Crypthecodinium cohnii.

Poly(ADP-ribose) polymerase and poly(ADP-ribose) glycohydrolase have been detected in chromatin extracts from the dinoflagellate Crypthecodinium cohnii. Poly(ADP-ribose) glycohydrolase was detected by the liberation of ADP-ribose from poly(ADP-ribose). Poly(ADP-ribose) polymerase was proved by (a) demonstration of phosphoribosyl-AMP in the phosphodiesterase digest of the reaction product, (b) demonstration of ADP-ribose oligomers by fractionation of the reaction product on DEAE-Sephadex. The (ADP-ribose)-protein transfer is dependent on DNA; it is inhibited by nicotinamide, thymidine, theophylline and benzamide. The protein-(ADP-ribose bond is susceptible to 0.1 M NaOH (70%) and 0.4 M NH2OH (33%). Dinoflagellates, nucleated protists, are unique in that their chromatin lacks histones and shows a conformation like bacterial chromatin [Loeblich, A. R., III (1976) J. Protozool. 23, 13--28]; poly(ADP-ribose) polymerase, however, has been found only in eucaryotes. Thus our results suggest that histones were not relevant to the establishment of poly(ADP-ribose) during evolution.

Chemical Phenomena↗
PubMed1984

Quantitative representation of all T cells committed to develop into cytotoxic effector cells and/or interleukin 2 activity-producing helper cells within murine T lymphocyte subsets.

A limiting dilution culture system based on stimulation with concanavalin A (Con A) has been used to study the quantitative distribution of helper and of cytotoxic precursor cells in Lyt-2-defined subpopulations of murine T cells. Virtually all of the selected Lyt-2+ and Lyt-2-T cells grow and expand to large clonal colonies within an 8-9-day culture period. Our data show that upon stimulation with Con A, 90% of the Lyt-2-T cells were capable to produce interleukin 2 (IL 2) activity. In addition, IL 2 activity is produced by 8-10% of Lyt-2+ T cells. However, at the clonal level, the average of the IL2 activity produced by Lyt-2+ T cells is about 8-fold less as compared to Lyt-2-T cells. Precursors of cytotoxic T cells were almost exclusively found in the Lyt-2+ population, of which about 70% displayed lytic activity in a lectin-dependent cytolysis test. For the vast majority of clones analyzed the capacity to produce IL 2 activity and the capacity to express lytic activity, was found to be mutually exclusive. A minority of clones (less than 3%) was found to simultaneously produce IL 2 activity and to express cytotoxicity. These latter cells are therefore considered as bifunctional T cells.

Animals↗
PubMed1984

T-T cell interactions during in vitro cytotoxic T cell responses. VI. The role of T cell-derived colony-stimulating factor in helper T cell activation.

A limiting dilution culture system has been used to analyze the role of T cell-derived colony stimulating factor (CSF) during the activation of IL 2-producing helper T lymphocytes (HTL). EL4 thymoma-derived supernatant (EL4-SN) increased about 4-fold the frequency of HTL precursors responding to metabolically active allogeneic stimulator cells. Upon biochemical separation this biological activity within the EL4-SN segregated from interleukin 2 (IL 2) and gamma interferon but was associated with or identical to CSF. Further, a comparable rise in HTL precursor frequencies was observed when semipurified interleukin 1 (IL 1) derived from the P388 D1 cell line was added to limiting dilution cultures. In contrast to IL 1, semipurified CSF failed to facilitate the activation of HTL precursors when heat-treated allogeneic spleen cells were used as stimulator cells. Because EL4-derived CSF was found to induce IL 1 production by macrophages we conclude that T cell-derived CSF amplifies, via stimulation of antigen-presenting cells the number of inducible HTL precursors. Therefore, the CSF/IL 1-dependent increase in HTL precursor frequencies reported here may reflect the differential activation threshold of HTL-precursors, most of which will not be activated by antigen per se but only in presence of additional cytokines.

Animals↗
PubMed1984

The action of anticlastogens in human lymphocyte cultures and its modification by rat liver S9 mix. I. Studies with AET and sodium fluoride.

The action of beta-aminoethylisothiouronium bromide hydrobromide (AET) and sodium fluoride (NaF) on the clastogenic activity of Trenimon, cyclophosphamide, and bleomycin was tested on cultures of human peripheral lymphocytes with and without the addition of rat liver S9 mix. In addition, the influence of both anticlastogens on the SCE-inducing activity of Trenimon and cyclophosphamide was examined under the same conditions. In the absence of S9 mix both substances displayed the known anticlastogenic action when TR was the standard clastogen but acted coclastogenically in the experiments with BM. Under the influence of rat-liver S9 mix this action on TR-induced chromosome damage was decreased and only a slight anticlastogenic effect was observed in the experiments with activated cyclophosphamide. S9-activated BM lost some of its strong chromosome-damaging effect and AET proved clearly anticlastogenic under these test conditions. AET displayed a slight decreasing effect on SCE induced by TR, but had no effect on CP-induced SCE. No anti-SCE effect at all was found in the experiments with NaF. Detailed analyses revealed different actions of both anticlastogens on the different types of structural chromosome damage.

Animals↗
PubMed1984

Combined effect of diethyldithiocarbamate (DDC) and modest hyperthermia on Chinese hamster (V79) cell survival and DNA strand break repair following photon irradiation.

Previous studies from our institution have shown that 10(-4) M DDC enhances the effects of radiation and of hyperthermia treatment at 43 degrees C on the killing of Chinese hamster (DON) cells. We herein report studies on the combined effect seen at more modest temperatures (41 degrees C) which can be achieved in humans by whole body heating without the need for general anesthesia. Treatment of V79 cells with DDC for 60 minutes at 37 degrees C or 41 degrees C had minimal toxicity at concentrations up to 5 X 10(-5) M. When cells were irradiated with single doses up to 1000 rad (137Cs, 350 rad/min), pre-incubation with 10(-4) M DDC had no effect on cell survival at 37 degrees C, but markedly decreased survival at 41 degrees C (D37 = 475 rad without DDC, 270 rad with DDC). The mechanism of this increased cell killing is not known. We observed, however, that there is no repair of DNA single strand breaks in DNA from irradiated V79 cells previously held at 41 degrees C in the presence of 10(-4) M DDC. Without DDC, repair of SSB was similar at 37 degrees C and 41 degrees C.

Animals↗