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H Wagner

Publications and source records attributed to H Wagner.

At least 343 records · Page 19Linked to original sources

Opportunist mycobacteria express ligands that stimulate production of human V gamma 9V delta 2 T lymphocytes.

Human gamma delta T cells are known to respond at high frequencies to pathogenic mycobacteria. Here we show that opportunistic strains of mycobacteria share with pathogenic mycobacteria the ability to trigger at high frequencies human V gamma 9V delta 2 T-cell-receptor-positive T lymphocytes. Stimulating ligands were present in part in a low-molecular-weight fraction of lysates from opportunistic mycobacteria, as has been found for pathogenic strains. These results support the view that postnatal exposure to ever-present opportunistic mycobacteria may be a driving force for the numerical expansion of the V gamma 9V delta 2 T-cell subset in adolescence.

Adolescent↗

Influence of temporal cues on acoustic motion-direction sensitivity of auditory neurons in the owl.

1. We studied the sensitivity of auditory neurons in the barn owl's brain stem to the direction of apparent acoustic motion. Motion stimuli were generated with an array of seven free-field speakers (Fig. 2). Motion-direction sensitivity was determined by comparing the number of spikes evoked by counterclockwise (CCW) motion with the number of spikes evoked by clockwise (CW) motion. A directionality index (DI) was defined to quantify the measurements. The statistical significance of the directional bias was determined by a chi 2 test that used the responses to stationary sounds as the null hypothesis. 2. During the search for acoustic neurons, dichotic stimuli were presented via earphones, and the sensitivity of the units for interaural time difference (ITD), interaural level difference (ILD), and frequency was measured. After a unit had been isolated, its response to moving and stationary free-field stimuli was recorded. Most of the neurons that responded to dichotic stimulation responded also to free-field stimulation. At 61 of the 211 recording sites, the response was motion-direction sensitive. 3. The spontaneous activity of all neurons was low, so that some 95% of the recorded activity was due to an excitation caused by the stimuli. 4. Neurons sensitive to the direction of motion were found in many nuclei of the auditory pathway such as the nuclei of the lateral lemniscus, the subnuclei of the inferior colliculus (IC), and the optic tectum (OT) (Figs. 3 and 5-8, Table 1). 5. In 61% of the motion-direction-sensitive neurons, the response to motion in the preferred direction was equal to the response to stationary sounds, whereas in 75% of the neurons, the response to motion in the null direction was lower than the response to stationary sounds (Table 2, Fig. 6). This observation suggested a null-direction inhibition as one important factor of generating motion-direction sensitivity. 6. Neurons having a high motion-direction sensitivity usually responded phasically, whereas tonically active neurons exhibited a low motion-direction sensitivity (Fig. 9). 7. Velocity tuning was broad (Fig. 7). A shallow peak appeared around 310 degrees/s within the range tested (125-1,200 degrees/s, 33 cells). 8. A silent gap between the bursts from successive speakers caused a decrease in motion-direction sensitivity. This decrease was linear with gap duration and depended on the apparent velocity (Figs. 10-13).(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

Antiasthmatic effects of Galphimia glauca, gallic acid, and related compounds prevent allergen- and platelet-activating factor-induced bronchial obstruction as well as bronchial hyperreactivity in guinea pigs.

A methanolic extract from Galphimia glauca (320 mg/kg, orally) inhibited acute bronchial reactions to allergen (ovalbumin, 10 mg/ml) and platelet-activating factor (PAF, 1 microgram/ml) inhalation challenges, but not to histamine or acetylcholine in spontaneously breathing guinea pigs. Furthermore, the PAF-induced bronchial hyperreactivity was markedly reduced. Gallic acid and related compounds as well as the flavonoid, quercetin, were identified as active compounds. Gallic acid, methyl gallate and quercetin showed significant effects after a single oral dose of 45 mg/kg, tetragalloyl quinic acid after 5 mg/kg. Continuous treatment of the animals with one certain fraction (GG II, 3 days, 3 x 2 mg/kg) containing all active compounds reduced allergen- and PAF-induced bronchial reactions by more than 70%.

Animals↗

Ploidy of lymphoblasts is the strongest predictor of treatment outcome in B-progenitor cell acute lymphoblastic leukemia of childhood: a Pediatric Oncology Group study.

PURPOSE: Using the technique of recursive partitioning and amalgamation analysis with verification, the Pediatric Oncology Group (POG) investigated the independent prognostic significance of previously published prognostic factors significantly associated with event-free survival (EFS) in B-progenitor cell acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Age, leukocyte count, sex, immunophenotype (expression of cytoplasmic immunoglobulin [Ig] and of surface antigens CD10 and CD34), and DNA index (ratio of the flow cytometry-determined DNA content of leukemia cells to that of normal diploid cells) were the variables used in the evaluation of four antimetabolite-based chemotherapy regimens in 1,535 children with the newly diagnosed B-progenitor cell ALL between February 1986 and May 1990. RESULTS: There were three subgroups at widely different risks of treatment failure. A DNA index greater than 1.16 was the most prognostic feature. The final prognostic subgrouping was as follows: (1) DNA index greater than 1.16; (2) DNA index less than or equal to 1.16, age less than 11.0 years, and leukocyte count less than 50 x 10(9)/L; and (3) DNA index less than or equal to 1.16, (age greater than 11.0 years, and/or leukocyte count greater than 50 x 10(9)/L). These groups made up 20%, 53%, and 27% of the patients and had 4-year EFS rates (SE) of 90.1% (6.3%), 80.5% (5.1%), and 50.4% (7.6%), respectively. CONCLUSIONS: Use of the DNA index, leukocyte count, and age--data that are relatively inexpensive and simple to obtain--may be sufficient to stratify patients with B-progenitor cell ALL for risk-directed therapy. Patients at an extremely low risk of failing therapy (approximately 20% of cases in this study) can thus be identified and spared the toxic short-term and late effects of more intensive therapies that may be needed for children with less favorable clinical and biologic features.

Adolescent↗

Circadian variation of the phagocytic activity of polymorphonuclear leukocytes and of various other parameters in 13 healthy male adults.

Twenty-four different laboratory parameters including the phagocytic activity (phagocytic index) of polymorphonuclear leukocytes (PMNs) and various hematologic variables were investigated in 13 young healthy men during Spring 1988 in Munich, Germany. Venous blood of these volunteers was obtained under standardized conditions at 4-h intervals over a 24-h span. All parameters were analyzed by the single cosinor method and by a Kruskal-Wallis analysis of variance (ANOVA). Statistically significant circadian rhythms were found for the number of circulating lymphocytes and leukocytes (WBCs), potassium, systolic blood pressure, phagocytic index, Quick test, heart rate, and rectal body temperature (p less than 0.05; single cosinor). For all of these parameters except WBCs, rectal body temperature, and Quick test, a temporal variation was confirmed by the ANOVA (p less than 0.05; phagocytic index: p = 0.05). The circadian acrophases of WBC, number of circulating lymphocytes, and phagocytic index were all found at about 01:00 h. This temporal coincidence of the acrophases of the phagocytic index and the number of circulating lymphocytes may reflect the modulation of phagocytosis by T lymphocytes that release cytokines known to stimulate the phagocytic activity of PMNs.

Adult↗

The Benton test in school counselling diagnostics. An exploratory study.

The Visual Test is subject to a critical appraisal, according to the standards of psychological tests. Investigating the test results of clients from a school counselling service it is shown that this test does not comply with the requirements of item analysis and reliability; referring to validity this test might be useful to estimate the general intelligence of pupils.

Attention Deficit Disorder with Hyperactivity↗

[Anti-inflammatory activity of sabal fruit extracts prepared with supercritical carbon dioxide. In vitro antagonists of cyclooxygenase and 5-lipoxygenase metabolism].

The extract SG 291 (Talso, Talso uno) from the fruits of Sabal serrulata (syn.: Serenoa repens) prepared by supercritical fluid extraction with carbon dioxide is used for the treatment of benign prostatic hyperplasia (BPH) and non bacterial prostatitis. In the present work, the Sabal extract SG 291 was analyzed by gas chromatography and investigated for its inhibitory influence on the biosynthesis of inflammatory arachidonic acid metabolites. The extract SG 291 was found in vitro to be a dual inhibitor of the cyclooxygenase (IC50-value: 28.1 micrograms/ml) and 5-lipoxygenase pathway (IC50-value: 18.0 micrograms/ml). By alkaline hydrolysis, ether extraction and preparative thin layer chromatography the extract SG 291 was separated in three fractions containing acid lipophilic compounds (A), fatty alcohols (B) and sterols (C) as main components. Fraction A inhibited the biosynthesis of cyclooxygenase (CO) and 5-lipoxygenase (5-LO) metabolites in the same intensity as the native extract SG 291, while the fractions B, C and beta-sitosterol showed no inhibitory effect on both enzymes of the arachidonic acid pathways. Therefore, the CO and 5-LO inhibiting principle of Sabal serrulata extract SG 291 must be localized in the acidic lipophilic fraction (SLF). The CO and 5-LO inhibitory effects may give an explanation for the in vivo observed antiphlogistic and antiedematous activity of the lipophilic Sabal serrulata extract SG 291.

Carbon Dioxide↗

Triggering of CD8+ cytotoxic T lymphocytes via CD3-epsilon differs from triggering via alpha/beta T cell receptor. CD3-epsilon-induced cytotoxicity occurs in the absence of protein kinase C and does not result in exocytosis of serine esterases.

The requirement for protein kinase C (PKC) during triggering of murine CD8+ CTL was investigated. To this, CTL were depleted for PKC by pretreatment with PMA. This procedure neither influenced alpha/beta-TCR, CD3-epsilon, CD8, CD2, and lymphocyte function-associated Ag-1 expression, nor CTL-target cell conjugate formation. Although cytolytic effector function of PKC-depleted CTL triggered via alpha/beta-TCR structures was completely inhibited, target cell lysis induced via CD3-epsilon remained unaffected. Furthermore this PKC-independent cytolysis pathway was not associated with the release of serine esterases. Analyses at the clonal level revealed that PKC depletion blocked the cytolytic response of up to 95% of alpha/beta-TCR triggered CTL clones. The data suggest the existence of a distinct signaling pathway triggered via CD3-epsilon that is not associated with exocytosis of serine esterases and probably independent of PKC.

Animals↗

A major fraction of human intraepithelial lymphocytes simultaneously expresses the gamma/delta T cell receptor, the CD8 accessory molecule and preferentially uses the V delta 1 gene segment.

The frequency of T cell receptor (TcR) type and the variable gene segment expression in human intraepithelial lymphocytes (IEL) from the large intestinal mucosa were studied by flow cytometry and immunohistochemistry, and compared to those in peripheral blood lymphocytes (PBL) - or lamina propria lymphocytes (LPL). Employing anti-gamma/delta TcR and anti-alpha/beta TcR monoclonal antibodies (mAb), flow cytometric analysis revealed that a large fraction of IEL (37%) are gamma/delta T cells, whereas within LPL and PBL gamma/delta T cells comprise a minor population (4.6% and 3.8% respectively). At these sites the number of gamma/delta T cells labeled with anti-CD8 mAb were 58.3% (IEL), 43.3% (LPL) and 24.4% (PBL). In situ staining of serial sections of large intestine confirmed these results. Hence, these data suggest a selective accumulation of CD8+ gamma/delta T cells in the human epithelium of the large intestine. Furthermore, analysis of gamma/delta TcR bearing IEL+ disclosed a marked preponderance of cells using the V delta 1 gene segment, whereas gamma/delta TcR+ PBL preferentially express V delta 2. Strikingly, the majority of these V delta 1+ IEL bear the CD8 molecule on their surface. These results are taken as evidence for a selective localization of V delta 1+ CD8+ gamma/delta T cells in the epithelium of the large intestine.

Adult↗

Vaccination of class I major histocompatibility complex (MHC)-restricted murine CD8+ cytotoxic T lymphocytes towards soluble antigens: immunostimulating-ovalbumin complexes enter the class I MHC-restricted antigen pathway and allow sensitization against the immunodominant peptide.

In vivo induction of anti-ovalbumin (OVA) cytotoxic T cell responses was brought about in an MHC class I-restricted fashion by immunizing H-2b mice with OVA in immunostimulating complexes (ISCOM). ISCOM formation with the hydrophilic soluble protein OVA was achieved upon unmasking hydrophobic protein domains by treatment at low pH values. The effector cells induced were MHC restricted, specific for the immunodominant peptide of OVA (258-276), and expressed the CD8+ CD4- phenotype. These results suggest that ISCOM-based vaccines may be useful to direct hydrophilic soluble antigens into the MHC class I presentation pathway in order to vaccinate CD8+ T lymphocytes.

Animals↗

Dissection of signals controlling T cell function and activation: H7, an inhibitor of protein kinase C, blocks induction of primary T cell proliferation by suppressing interleukin (IL)2 receptor expression without affecting IL2 production.

T cell activation induced via cross-linking of the T cell receptor (TcR) stimulates hydrolysis of phosphatidylinositol to the second messengers diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). DAG is necessary for the activation and function of protein kinase C (PKC) which is suggested to play a key role in the cascade of signal transduction when translocated from the cytosol to the cell membrane. In this report, we investigated responses of resting vs. activated Ly-2+ and L3T4+ T lymphocytes in the presence of the PKC inhibitor H7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine]. H7 inhibited the induction of primary T cell proliferation, while interleukin 2 (IL 2) production was fully retained. The effect of the PKC inhibitor on primary T cells depended on the type of ligand interacting with the TcR: increasing doses of concanavalin A or of immobilized anti-CD3 monoclonal antibody (mAb), but not of anti-V beta 8 or of anti-TcR alpha/beta mAb, partly overcame the blockade, indicating a differential signaling compared to the former stimuli. The blockade of T cell proliferation by H7 was not due to an inhibition of PKC translocation, but occurred even 4-8 h after T cell induction and correlated with a significant reduction of IL 2 receptor (IL 2R) expression. In contrast, the mRNA levels of IL 2R and the cellular proto-oncogenes c-fos and c-myc were not affected. On activated T cells, H7 neither blocked proliferation nor IL2R expression. Consequently, H7 dissects the signal resulting in T cell proliferation from those governing the triggering of other T cell functions, i.e. IL 2 production, during primary responses of Ly-2+ or L3T4+ murine T lymphocytes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Plasmodium falciparum merozoites primarily stimulate the V gamma 9 subset of human gamma/delta T cells.

Peripheral blood-derived T cells from six unprimed caucasian donors were tested for the in vitro reactivity to Plasmodium falciparum merozoites (PFM). Without exception vigorous proliferative responses were observed within the donors tested. The frequency of PFM-reactive T cells ranged from 1/150-1/300. Phenotypic analysis of peripheral blood lymphocytes cultured in the presence of PFM revealed the preferential outgrowth of gamma/delta T cells, which represented within 7 days about 70% of the reactive T cell blasts. All reactive gamma/delta T cell blasts displayed the V gamma 9+ TcR phenotype. We conclude that human gamma/delta T cells respond vigorously to PFM, and that this property is confined to V gamma 9+ T cell subset.

Animals↗