Biomedical subjects

M Ernst

Publications and source records attributed to M Ernst.

At least 163 records · Page 9Linked to original sources

PubMed1993

Phenotypical and functional characterization of Fc gamma receptor I (CD64)-negative monocytes, a minor human monocyte subpopulation with high accessory and antiviral activity.

Fc gamma receptor I-positive (CD64+) and Fc gamma receptor I-negative (CD64-) monocytes were prepared from highly purified (elutriation-derived) human monocytes by cytofluorograph cell sorting, and a phenotypical and functional dissociation of the isolated CD64+ and CD64- monocyte subsets is demonstrated. Surface analyses revealed that the surface antigen pattern of CD64+ monocytes corresponds to the phenotype of typical unseparated monocytes. In contrast, CD64- monocytes are characterized by high expression of major histocompatibility complex (MHC) class I antigens (HLA-A, -B, -C) and MHC class II antigens (HLA-DR, -DP, -DQ), and low expression of the monocyte-specific marker CD14 which is found on nearly all CD64+ monocytes. However, 75% of the CD64- cells were found to be esterase-positive, and 85% were positive for the the CD64- cells were found to be esterase-positive, and 85% were positive for the monocyte/macrophage-specific intracellular antigen CD68. Furthermore, CD64- monocytes show significantly higher expression of CD45RA and Fc gamma receptor III (CD16) than CD64+ monocytes, but lack the natural killer cell markers CD56 and CD57. Functional studies showed that cells of the minor CD64- monocyte subset have a higher accessory cell capacity in antigen-driven T cell activation than CD64+ monocytes. CD64- monocytes pretreated with PPD (purified protein derivative of tuberculin) induced up to tentimes more interferon-gamma and also higher proliferation in responding autologous T cells than PPD-pretreated CD64+ monocytes. Similar results were obtained for T cells in mixed leukocyte reaction. Interferon-gamma release and proliferation of allogeneic lymphocytes were consistently higher in the presence of irradiated CD64- monocytes than of irradiated CD64+ monocytes. Furthermore, when CD64- and CD64+ monocytes were stimulated with Newcastle disease virus, we measured an up to 67-fold higher interferon-alpha release from CD64- than from CD64+ monocytes, indicating a higher anti-viral capacity of this subset. CD64- monocytes showed lower activity in the phagocytosis of unopsonized particles and also lower zymosan- or latex-induced chemiluminescence than CD64+ monocytes. These findings indicate that CD64- monocytes, although comprising only less than 10% of all peripheral blood monocytes, represent a monocyte subpopulation efficiently interacting in vitro with T cells and, additionally, are the major source of interferon-alpha.

Antigen-Presenting Cells↗

PubMed1993

Membrane surface proteinase 3 expression and intracytoplasmic immunoglobulin on neutrophils from patients with ANCA-associated vasculitides.

We studied the presence of proteinase 3 (PR3), myeloperoxidase (MPO) and elastase (HLE) on the plasma membrane of neutrophils in patients with biopsy-proven Wegener's disease (WG), pANCA-positive vasculitis, control patients (SLE, rheumatoid arthritis, ankylosing spondylitis), sepsis patients and healthy donors. We found an overexpression of PR3 on the cell surface of neutrophils in WG, ANCA-associated vasculitis and during infection (sepsis). Thus PR3 becomes accessible to ANCA. Furthermore we detected intracytoplasmic IgG antibodies in PMN from patients with WG by immunoelectron microscopy and direct immunofluorescence. Our findings support the pathophysiological role of ANCA.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1993

Induction of bacillus-Calmette-Guérin-activated killer cells from human peripheral blood mononuclear cells against human bladder carcinoma cell lines in vitro.

Cytotoxicity against two human bladder carcinoma cell lines (BT-A and BT-B) was investigated using human peripheral blood mononuclear cells (PBMC) stimulated with viable bacillus Calmette-Guérin (BCG) or sonicated BCG (s-BCG). We applied a cytotoxicity assay based on radioactive labelling of tumour cells by incorporation of L[3H]methionine. The results were compared with the cytotoxicity exerted by lymphokine-activated killer (LAK) cells generated by interleukin-2 (IL-2) and interferon gamma (IFN gamma). BCG-stimulated PBMC showed a cytotoxic potential against BT-A and BT-B comparable to that of IFN gamma-generated LAK cells, but this did not reach the level of IL-2-generated LAK cells. We termed these cytotoxic effectors BCG-activated killer (BAK) cells. In contrast to their cytotoxicity against bladder tumour cells, BAK cells did not differ from unstimulated PBMC in the killing of K562 cells. Only viable but not sonicated BCG was able to induce cytotoxicity against BT-A and BT-B. We could demonstrate the presence of the cytokines IFN gamma, IL-2, tumour necrosis factor alpha (TNF alpha) and TNF beta in the supernatants harvested during the generation of BAK cells. Monoclonal antibodies neutralizing IFN gamma were able to inhibit BCG-mediated cytotoxicity, giving evidence of the involvement of IFN gamma in the induction of BAK cells. Furthermore, we performed experiments to investigate the cytotoxic potential of distinct cell populations. The cells effective in BCG-activated killing of bladder tumour cells could be localized within the CD8+/CD56+ lymphocyte subset. CD4+ cells and macrophages did not exhibit cytolytic activity. Our findings imply that the activation by BCG of CD8+/CD56+ killer cells might be an important antitumoral mechanism during BCG therapy against superficial urothelial bladder cancer.

BCG Vaccine↗

PubMed1993

Dissecting the immunobiological effects of Bacillus Calmette-Guérin (BCG) in vitro: evidence of a distinct BCG-activated killer (BAK) cell phenomenon.

Several immunobiological effects of intravesical bacillus Calmette-Guérin (BCG) during immunotherapy of superficial bladder cancer have been suggested as possible mediators of the mode of action. In an attempt to elucidate which of these effects is relevant to tumoricidal activity, an in vitro cytotoxicity assay was employed in which the direct effects of BCG and of cytokines against four transitional carcinoma cell lines were studied. Furthermore, peripheral blood mononuclear cells (PBMNC) were analyzed for their cytotoxic potential against these target cells. We found that none of the cytokines interleukin-1, interleukin-2, interferon-gamma, tumor necrosis factor alpha, lymphotoxin, or BCG alone were cytotoxic against the bladder carcinoma cell lines. However, a pronounced cytotoxicity against these targets resistant to natural killer cells could be induced in PBMNC by coincubation with viable BCG. We termed this the BCG-activated killer (BAK) cell phenomenon. In contrast to lymphokine-activated (LAK) cells, these BAK cells needed prolonged activation for 7 days and did not enhance the cytotoxicity against K562 target cells sensitive to natural killer cells. Nonviable, heat-inactivated BCG was significantly less effective, and sonificated fractions of BCG were not effective in stimulating PBMNC towards BAK cell activity. In vitro dissection of effects observed during BCG intravesical therapy may give more insight into the mode of action of BCG and may help to separate primary tumoricidal effector mechanisms from secondary concomitant phenomena. Further characterization of the BAK cell may result in an improvement of intravesical BCG immunotherapy.

BCG Vaccine↗

PubMed1993

Acute dystonic reaction with low-dose pimozide.

It is essential to recognize individual susceptibility to neuroleptic-induced side effects for treatment guidelines. This paper reports on a 6.9-year-old autistic male who developed repeated episodes of acute dystonic reactions associated with pimozide administration at the doses of 0.096 mg/kg/day and 0.032 mg/kg/day and 32 hours following pimozide withdrawal, as well as during subsequent thioridazine administration. It draws the clinician's attention to unusual susceptibility to extrapyramidal side effects and suggests that if a child shows this type of susceptibility to one neuroleptic, he/she may react similarly to other neuroleptics as well.

Autistic Disorder↗

PubMed1993

Naltrexone in autistic children: behavioral symptoms and attentional learning.

OBJECTIVE: To assess critically the short-term efficacy and safety of naltrexone in autistic children and its effects on discrimination learning in the laboratory. METHOD: A parallel group design was employed. After a 2-week placebo baseline period, children were randomly assigned either to naltrexone or to placebo for a period of 3 weeks followed by a one-week posttreatment placebo period. Multiple raters and rating scales were employed in a variety of conditions. Forty-one children, all inpatients, ages 2.9 to 7.8 years, completed the study. Naltrexone reduced hyperactivity and had no effect on discrimination learning in the laboratory. There was a suggestion that it had a beneficial effect on decreasing self-injurious behavior. Untoward effects were mild and transient. CONCLUSION: In the present study, naltrexone significantly reduced only hyperactivity, and no serious untoward effects were observed. The effectiveness of naltrexone in the treatment of autism and self-injurious behavior requires additional assessment in a sample of children with moderate to severe self-injurious behavior.

Attention↗

PubMed1993

Specific activation of human peripheral blood gamma/delta + lymphocytes by sonicated antigens of Mycobacterium tuberculosis: role in vitro in killing human bladder carcinoma cell lines.

Tumour regression induced in cancer patients by local instillation of Bacillus Calmette-Guérin (BCG) into the bladder has been considered to be mainly mediated by activated cellular immunity and inflammatory reactions. In the present study we investigated the cytotoxicity of T cells bearing gamma/delta T-cell receptors (gamma/delta + cells) against bladder carcinoma cells in vitro. Long-term cultured gamma/delta + T-cell lines from peripheral blood lymphocytes of healthy donors were established by stimulation with sonicated cell wall-associated antigens of Mycobacterium tuberculosis (SMA). These gamma/delta + T cells lack the natural killer (NK) markers CD16 and CD56, as determined by flow cytometry. The SMA-specific gamma/delta + T cells exhibited profound cytotoxicity against two NK-resistant bladder tumour cell lines as well as against NK-sensitive tumour cells in a non-major histocompatibility complex-restricted manner. The pattern of tumour cells killed by gamma/delta + T cells differed significantly from those of NK cells and lymphokine-activated killer LAK cells. Furthermore, we tested the effects of recombinant human cytokines, including interleukin (IL)-1, IL-2, IL-4, IL-6, interferon (IFN)-gamma and tumour necrosis factor (TNF), on gamma/delta + T-cell-mediated cytotoxicity. It was shown that the addition of recombinant TNF in co-incubation could augment gamma/delta + T-cell-mediated killing of two bladder tumour cell lines, but not of cells of the erythroleukaemia cell line K562. Based on these results it was concluded that mycobacterial antigens could specifically activate resting gamma/delta + T cells. The cytotoxicity of gamma/delta + T cells against bladder tumour cells and its selective enhancement by TNF may be an important mechanism involved in bladder tumour regression induced by intravesical instillation of BCG.

Antigens, Bacterial↗

PubMed1993

Pentoxifylline: a potent inhibitor of IL-2 and IFN-gamma biosynthesis and BCG-induced cytotoxicity.

In the present study we investigated the influence of pentoxifylline (POF) on bacillus Calmette-Guérin (BCG)- and phytohaemagglutinin (PHA)-induced DNA synthesis and cytokine release, and BCG-induced cytotoxicity of human peripheral blood mononuclear cells (PBMC). DNA synthesis of PBMC stimulated with either BCG or PHA was inhibited by POF. We also demonstrated that the addition of POF led to a POF dose-dependent decrease of the release of the cytokines interleukin (IL)-2, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). The release of IL-6 remained unaffected. With respect to the inhibition of BCG-induced IL-2 and IFN-gamma release POF is active at the transcriptional (mRNA) level, as found by polymerase chain reaction (PCR). However, PHA-induced mRNA expression of these lymphokines is not affected by POF. Thus, the existence of a post-transcriptional regulation of PHA-induced cytokine release by POF can be assumed. The observed inhibition of cytokine release is correlated with a potent inhibitory effect of POF on BCG-induced cytotoxicity against bladder tumour cell lines. This effect is reversible.

Cells, Cultured↗

PubMed1993

Plasma beta-endorphin levels, naltrexone, and haloperidol in autistic children.

Plasma beta-endorphin levels were measured in 13 autistic children, aged 3.67 to 11.67 years at the end of treatment (naltrexone, haloperidol, pimozide, or placebo) and in 5 of the 13 children also at baseline. Baseline plasma beta-endorphin levels were lower than those reported in the literature. There was a strong correlation between plasma beta-endorphin levels and severity of sterotypies in all children. Naltrexone did not seem to have a specific effect on plasma beta-endorphin levels; short-term haloperidol treatment was associated with an increase, whereas long-term haloperidol treatment seemed to have a depressive effect on plasma beta-endorphin levels, which rose after withdrawal of haloperidol.

Autistic Disorder↗

PubMed1993

[Primary hyperparathyroidism in intrathyroid parathyroid cancer].

Parathyroid carcinoma is a rare cause of hyperparathyroidism. Histological differentiation from parathyroid adenoma may be difficult and is rarely achieved intraoperatively. Parathyroid carcinomas are sometimes localized heterotopically. We report a case of parathyroid cancer in the left thyroid lobe. Surgical therapy should include en bloc resection of the tumor, the thyroid lobe and the parathyroid tissue.

Adenoma↗

PubMed1993

[Changes in surgery of diverticulitis].

This retrospective study investigates the surgical progress in the treatment of diverticular disease during the last two decades. We reviewed 304 patients (149 women and 155 men) operated for diverticular disease from 1970-1992 at the Surgical Clinic of Steglitz Medical Center, Free University of Berlin. Comparing the results between the first and the second decade, we observed a significant increase in the total number of patients who have been treated surgically (from 118 to 186) and in the proportion of elective surgery (from 45% to 57%). In the second decade, early elective resection in selected patients with a severe diverticulitis and primary resection for perforated diverticulitis were the procedures of choice. Through this concept the over-all operative mortality rate could be reduced from 24% in the first to 7% in the last decade of this report.

Aged↗

PubMed1992

Cytokines involved in monocyte mediated tumor cell death and growth inhibition in serum-free medium.

In a serum-free culture system, the release of TNF, lI-1, lI-6, IFN-alpha, and IFN-beta during interaction of elutriated human monocytes (MO) with human tumor cells (TC) was studied by ELISA-technique. Contributions of these cytokines to inhibition of TC-growth and to induction of TC-death by supernatants (SU) gained from such MO/TC-interaction cultures were investigated using affinity chromatography for removal of individual cytokines. Although the TC used are relatively insensitive to recombinant human TNF, withdrawal of TNF causes 50% to 75% reduction of SU-induced TC-death rates, suggesting that susceptibility to TNF is raised during MO/TC-interaction by the other cytokines. Individual removal of other cytokines does not cause reduction of SU-mediated TC-death. However, combined withdrawal of lI-1 and IFN-alpha/beta causes in 2 of 4 TC-lines significant reduction of TC-death. Combined removal of TNF, IFN-alpha/beta, lI-1, and lI-6 leads to complete prevention of SU-mediated growth inhibitory and lytic effects, suggesting that besides these cytokines other signals are not involved significantly. SU-effects can be mimicked by appropriate combinations of authentic cytokines. The response of TC to SU- or cytokine-exposure is strikingly dependent on TC-density, leading at subconfluent TC-density exclusively to inhibition of growth and at postconfluent TC-density to induction of cell death. The principal effect of SU or cytokine combinations in this context seems to be the activation of growth inhibitory signal transduction pathways leading to TC-death in postconfluent TC-populations exclusively if growth stimulatory pathways are activated at the same time. Mouse L cells do not follow this reaction pattern: Their death is exclusively dependent on the presence of TNF in SU and they die upon SU-exposure at postconfluent as well as at subconfluent cell density.

Animals↗

PubMed1992

Cognitive abilities of patients with Lesch-Nyhan disease.

Parents of 42 patients with Lesch-Nyhan disease completed a questionnaire systematizing caregiver observations of the subject's behavior during a wide variety of daily events. Responses were grouped in nine categories reflecting different aspects of cognitive skills. Only 1 boy appears to have any significant generalized cognitive impairment. The patients' memory for both recent and past events is excellent, their emotional life has a normal range of reactions and is appropriate; they have good concentration, are capable of abstract reasoning, have good self-awareness, and are highly social. However, they are behind in academic ability, with only 15% at grade level for math and reading. Implications for designing educational activities, parenting or caregiver strategies, and research methodology are discussed.

Achievement↗

PubMed1992

Human monoclonal antibodies for the differentiation of Rh-D categories.

With the introduction of human monoclonal antibodies against antigens of the Rh-system it was possible to solve a series of problems, as, for instance, the permanent availability of reagents. Another problem, the classification of D-categories with a panel of specific monoclonal antibodies, also might be solved by the production of such antibodies. Especially the classification of Cat. VI-cells is of great importance. We present a panel of five human monoclonal antibodies useful for the definition of Rh-D categories. The antibodies are designated as BS221, BS227, BS228, BS230 and BS231. By positive or negative reactions with expected category cells it is possible to determine the corresponding category. All Cat. VI-cells of a defined panel could be identified. Of particular interest is the antibody BS221 due to its reactivity with Cat. VI-cells. The fact, however, that BS221 is missing the detection of some Cat. VI-cells indicates a further subdivision of Cat. VI.

Antibodies, Monoclonal↗

PubMed1992

Results of the DGTI workshop on the evaluation of the reactivity of monoclonal anti-D.

All D+ samples were detected by all monoclonal antibodies without problems. Very few of the 3000 D- samples showed a +/- to ++ reaction with some of the IgG type mabs using the Coombs technique. It is still open whether these are specific reactions with weak positive samples, which were negative with polyclonal sera. IgM type mabs detected up to 100% of the Du samples dependent on the Rh-phenotype and the technique used (CCDuee greater than CcDuee greater than ccDuEe). Most of the CCDuee samples reacted very strong and should no longer be regarded as Du.

Antibodies, Monoclonal↗

PubMed1992

Results of the DGTI workshop on the evaluation of the reactivity of monoclonal anti-D.

All D+ samples were detected by all monoclonal antibodies (mabs) without any problem. Very few of the 3,000 D- samples showed a +/- to ++ reaction with some of the IgG type mabs using the Coombs technique. It is still open whether these are specific reactions with weakly positive samples, which were negative with polyclonal sera. IgM type mabs detected up to 100% of the Du samples dependent on the Rh phenotype and the technique used (CCDuee > CcDuee > ccDuEe). Most of the CCDuee samples reacted very strongly and should no longer be regarded as Du.

Antibodies, Monoclonal↗

PubMed1992

Human monoclonal antibodies for the differentiation of RhD categories.

With the introduction of human monoclonal antibodies against antigens of the Rh system it was possible to solve a series of problems as, for instance, the permanent availability of reagents. Another problem, the classification of D categories with a panel of specific monoclonal antibodies, also might be solved by the production of such antibodies. Especially the classification of cat. VI cells is of great importance. Here we are presenting a panel of 5 human monoclonal antibodies useful for the definition of Rh-D categories. The antibodies are designated as BS221, BS227, BS228, BS230 and BS231. By positive or negative reactions with expected category cells it is possible to determine the corresponding category. All cat. VI cells of a defined panel could be identified. Of particular interest is the antibody BS221 due to its reactivity with cat. VI cells. The fact, however, that BS221 misses the detection of some cat. VI cells indicates a further subdivision of cat. VI.

Antibodies, Monoclonal↗

PubMed1992

Pimozide in autistic children.

This open pilot study explored the efficacy and safety of pimozide, over a 3-week period, in hospitalized autistic children. Eight males, ages 4.2 to 8.3 years, completed the study. Intellectual functioning ranged from moderate to profound mental retardation. Symptoms included severe withdrawal, stereotypies, hyperactivity and/or hypoactivity, aggressiveness, and temper tantrums. Therapeutic daily doses of pimozide ranged from 3.0 mg to 6.0 mg with a mean of 4.9 mg (0.12-0.32 mg/kg; mean, 0.22). Laboratory studies including electrocardiogram and liver function tests remained within normal limits. Untoward effects were minimal and transient. Decreases of behavioral symptoms were evidenced on all measures including the Children's Psychiatric Rating Scale, Clinical Global Impressions, and Global Clinical Judgments Scale (consensus rating). Of the 5 hypoactive children, 4 showed a decrease in hypoactivity, whereas 1 child showed worsening. These findings are promising and indicate the need for further study.

Autistic Disorder↗