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Biomedical subjects

H Wagner

Publications and source records attributed to H Wagner.

At least 19 recordsLinked to original sources
PubMed1992

V delta 1+ subset of human gamma delta T cells responds to ligands expressed by EBV-infected Burkitt lymphoma cells and transformed B lymphocytes.

Human gamma delta T cells of peripheral blood can be divided in two groups in terms of their TCR as well as their behavior upon in vitro stimulation. The major subset expresses the TCR V-segments V gamma 9 and V delta 2 and proliferates in response to ligands revealed by various microorganisms, and the cell line Daudi in addition. The minor group is less homogenous on the gamma-chain but is almost completely identified by mAb against the V delta 1 segment; there is no ligand known to promote growth of these cells. Here we demonstrate that gamma delta T cells out of this subgroup are strongly stimulated in vitro by cells from several Burkitt's lymphoma cell lines. EBV infection of the Burkitt's lymphoma cell lines enhanced the stimulatory ability towards the T cells. Although EBV infection influenced the expression of a variety of cell surface molecules including ICAM-1 and LFA-3, no correlation to the gamma delta T cell-stimulating capacity became apparent. We conclude that Burkitt's lymphoma cells and transformed B cells express ligands of cellular origin for a hitherto poorly characterized subgroup of human gamma delta T cells.

B-Lymphocytes↗
PubMed1992

Improved sample preparation for the testosterone hydroxylation assay using disposable extraction columns.

The preparation of samples for injection into a high-performance liquid chromatograph from assay mixtures for the determination of cytochrome P-450-dependent testosterone hydroxylation has been substantially facilitated. By replacing the multiple cumbersome extraction steps of the conventional method with a single column extraction the time for sample preparation was reduced from hours to minutes. The new procedure also yields better recoveries for most of the testosterone metabolites than the original protocol. The use of extraction columns for sample preparation allows the simultaneous treatment of a large number of samples or even the automation of the whole assay procedure. The modified procedure is a straightforward, easy-to-perform method that should greatly facilitate the implementation of the testosterone hydroxylation assay for sharply discriminating between many individual cytochrome P-450 species in routine enzyme diagnostics.

Chromatography↗
PubMed1992

A lectin-binding, protease-resistant mycobacterial ligand specifically activates V gamma 9+ human gamma delta T cells.

Bacterial (exogeneous) superantigens have been defined as bifunctional proteinaceous molecules. They bind to class II MHC molecules of presenting cells and engage with particular TCR-V beta gene elements, thereby activating alpha beta T cells in a V beta-oriented fashion. In previous studies we have elucidated that gamma delta T cells exhibit a propensity to vigorously respond toward mycobacterial Ag. Intrigued by this finding we now analyzed whether mycobacteria express a superantigen for a subset of human gamma delta T cells definable by the selective use of TCR-V gene elements. Here we describe that a protease-resistant, low m.w. (1 to 3 kDa) component of mycobacteria selectively activates gamma delta T cells expressing TCR-V gamma 9 gene segments. Contained in mycobacterial lysates it stimulates TCR-V gamma 9-positive gamma delta T cells at a frequency of 1/6. Stimulation is critically dependent on the presence of class II MHC-positive presenting cells, the important structure being HLA-DR molecules. The fine specificity of the V gamma 9 seeking mycobacterial ligand differs from the gamma delta T cell-stimulating structures expressed by Daudi cells. In addition, the mycobacterial, V gamma 9-seeking ligand is bound selectively to lectins such as UEAI, SBA, and DBA. We conclude that mycobacteria contain a component that acts as a superantigen for human gamma delta T cells and we believe it is this property that explains the vigorous participation of gamma delta T cells in mycobacterial infections.

Antigens, Bacterial↗
PubMed1992

T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor.

Because mice are more resistant than humans to the pathogenic effects of bacterial toxins, we used D-Galactosamine- (D-Gal) sensitized mice as a model system to evaluate potential toxic shock symptoms triggered by the superantigen staphylococcal enterotoxin B (SEB). We show that similar to endotoxin (lipopolysaccharide) [LPS], the exotoxin SEB causes lethal shock within 8 h in D-Gal-sensitized mice, inducing 100% and about 50% lethality with 20 and 2 micrograms SEB, respectively. The lethal shock triggered by the superantigen SEB is mediated by T cells, a conclusion based on the observation that T cell repopulation of SCID mice conferred sensitivity to SEB. Since CSA also conferred protection, the role of T cell-derived lymphokines in mediating lethal shock was evaluated. Within 30-60 min after SEB injection, serum tumor necrosis factor (TNF) levels peaked, followed immediately by interleukin-2 (IL-2). Serum-borne lymphokines were detected well in advance of signs of T cell activation, as assessed by IL-2 receptor expression of SEB-reactive V beta 8+ T cells. Passive immunization with anti-TNF-alpha/beta-neutralizing monoclonal antibody also conferred protection, indicating that it is TNF which is critical for initiating toxic shock symptoms. Taken together, this study defines basic differences between endotoxin (LPS)- and exotoxin (SEB)-mediated lethal shock, in that the former is mediated by macrophages and the latter by T cells. Yet the pathogenesis distal to the lymphokine/cytokine-producing cells appears surprisingly similar in that TNF represents a key mediator in inducing shock.

Animals↗
PubMed1992

High-speed rotational angioplasty-induced echo contrast in vivo and in vitro optical analysis.

High-speed rotational angioplasty is being evaluated as an alternative interventional device for the endovascular treatment of chronic coronary occlusions. It has been postulated that this type of angioplasty device may produce particulate debris or cavitations that induce myocardial ischemia. To determine the clinical presence of myocardial ischemia during rotational angioplasty, echocardiographic monitoring for wall motion abnormalities was performed in 9 patients undergoing rotational atheroablation using the Auth Rotablator for 10-sec intervals at 150,000 and 170,000 rpm. No wall motion abnormalities were detected in 5 patients evaluated with transesophageal echocardiography or in 4 patients monitored transthoracically, although AV block developed in one patient. Video intensitometry of the myocardial contrast effect for rotation times ranging from 3 to 20 sec found transient contrast enhancement of the myocardium supplied by the treated vessel. Intensity varied over time with half-time decay between 5.6 and 40 sec, indicating the likelihood of microcavitation. An in vitro model was constructed to measure the cavitation potential of the Auth Rotablator. A burr of 1.25 mm diameter rotating at 160,000 rpm achieves a velocity in excess of the 14.7 m/sec critical cavitation velocity. Testing the device in fresh human blood and distilled water produced microcavitations responsible for the enhanced echo effect, with the intensity and longevity of cavitation more pronounced in blood and proportional to the rotation time and speed. The mean size of the microcavitation bubbles in water was 90 +/- 33 (52-145) microns measured from photographs taken with a copper vapour laser emitting light pulses of 50 nsec duration as light source. The mean velocity of bubbles was found to be 0.62 +/- 0.30 ranging from 0.23 to 1.04 m/sec. It was measured via the motion of the bubbles during 5 laser pulses within 800 nsec. Clearly, microcavitations are associated with enhanced myocardial echo contrast effect.

Angioplasty, Balloon, Coronary↗
PubMed1992

On the ability of neurons in the barn owl's inferior colliculus to sense brief appearances of interaural time difference.

This paper investigates the ability of neurons in the barn owl's (Tyto alba) inferior colliculus to sense brief appearances of interaural time difference (ITD), the main cue for azimuthal sound localization in this species. In the experiments, ITD-tuning was measured during presentation of a mask-probe-mask sequence. The probe consisted of a noise having a constant ITD, while the mask consisted of binaurally uncorrelated noise. Collicular neurons discriminated between the probe and masking noise by showing rapid changes from untuned to tuned and back to untuned responses. The curve describing the relation between probe duration and the degree of ITD-tuning resembled a leaky-integration process with a time constant of about 2 ms. Many neurons were ITD-tuned when probe duration was below 1 ms. These extremely short effective probe durations are interpreted as evidence for neuronal convergence within the pathway computing ITD. The minimal probe duration necessary for ITD-tuning was independent of the bandwidth of the neurons' frequency tuning and also of the best frequency of a neuron. Many narrowly tuned neurons having different best frequencies converge to form a broad-band neuron. To yield the short effective probe durations the convergence must occur in strong temporal synchronism.

Acoustic Stimulation↗
PubMed1992

Inhibition of cholesterol synthesis in vitro by extracts and isolated compounds prepared from garlic and wild garlic.

Using a modified liver homogenate model to assay for the inhibition of cholesterol biosynthesis, different garlic and wild garlic extracts as well as pure compounds isolated from them were investigated for their influence on cholesterol synthesis. Chloroform and acetone/chloroform extracts of garlic and wild garlic inhibited cholesterol synthesis 44-52% at a concentration of 166 micrograms/ml, while the 5 individual sulfur-containing compounds ajoene, methylajoene, allicin, 2-vinyl-4H-1,3-dithiin and diallydisulfide inhibited cholesterol synthesis by 37-72% (10(-3) M corresponding to 234, 208, 162, 144, 146 micrograms/ml, respectively). Ajoene, 2-vinyl-4H-1,3-dithiin and allicin show IC50 values of 6.4, 7.2 and 9.4 x 10(-4) M, respectively. The results demonstrate that garlic and wild garlic may reduce serum cholesterol levels primarily by inhibiting cholesterol synthesis if taken in sufficient amount and that this effect arises from a mixture of multiple compounds from the sulfur-containing class of thiosulfinates, ajoenes and dithiines. Wild garlic extracts showed nearly identical efficiency to garlic extracts.

Animals↗
PubMed1992

Triterpene saponins from the roots of Ampelozizyphus amazonicus.

A new triterpene saponin was isolated from the roots of Ampelozizyphus amazonicus together with the known 3-O-beta-D-glucopyranosyl-20-O-alpha-L-rhamnopyranosyljujubogenin and the known triterpenes melaleucic acid, 3 beta,27 alpha-dihydroxylup-20(29)-en-28 beta-oic acid, betulinic acid, betulin, lupeol. The structure of this saponin was elucidated as 3-O-[beta-D-glucopyranosyl(1----2)alpha-L-arabinopyranosyl]- 20-O-alpha-L-rhamnopyranosyljujubogenin by spectral analysis and chemical transformations.

Carbohydrate Sequence↗
PubMed1992

Immunologically active metallic ion-containing polysaccharides of Achyrocline satureioides.

Two homogeneous, metallic ion-containing pectic polysaccharides with mean M(r)s of 7600 and 15,000 were isolated from dried aerial parts of Achyrocline satureioides by anion exchange column chromatography on DEAE-Sepharose CL-6B and gel filtration column chromatography on Fractogel TSK HW-50 (S). The structures, as determined by methylation analysis, carboxyl reduction, and partial acid hydrolysis, were shown to be rhamnogalacturonans. Both pectins show a pronounced anticomplementary effect in vitro. The larger carbohydrate AS 4 of higher M(r) exerts anti-inflammatory activity and a strong enhancement of phagocytosis in vivo.

Carbohydrate Sequence↗
PubMed1992

Barn owls have symmetrical accommodation in both eyes, but independent pupillary responses to light.

We have studied accommodation behaviour in the barn owl (Tyto alba). By defocussing one eye with various spectacle lenses and recording the refractive state in both eyes continuously during pecking, we found that the owls' accommodation was symmetrical in both eyes, with no regard to the power of the lens used. Even with no visual input to one eye, the amount of accommodation was always identical in both eyes. On the other hand, pupillary responses to light were independent. This finding differs from an earlier observation in the chicken, where both accommodation and pupillary responses were found to be independent. The result is discussed with regard to current knowledge on the central pathways for control of accommodation and pupillary responses in birds.

Accommodation, Ocular↗
PubMed1992

Comparative pharmacological investigations of Allium ursinum and Allium sativum.

Extracts of wild garlic (Allium ursinum) and garlic (A. sativum) with defined chemical compositions were investigated for their in vitro inhibitory potential on 5-lipoxygenase (LO), cyclooxygenase (CO), thrombocyte aggregation (TA), and angiotensin I-converting enzyme (ACE). The inhibition rates as IC50 values of both extracts for 5-LO, CO, and TA showed a good correlation with the %-content of the major S-containing compounds (thiosulfinates and ajoenes) of the various extracts. In the 5-LO and CO test the garlic extracts are slightly superior to the wild garlic extracts whereas, in the TA test, no differences could be found. In the ACE test the water extract of the leaves of wild garlic containing glutamyl-peptides showed the highest inhibitory activity followed by that of the garlic leaf and the bulbs of both drugs. The comparative studies underline the usefulness of wild garlic as a substitute of garlic.

Allium↗
PubMed1992

Antihepatotoxic C-glycosylflavones from the leaves of Allophyllus edulis var. edulis and gracilis.

From the leaves of Allophyllus edulis var. edulis and Allophyllus edulis var. gracilis nine C-glycosylflavones have been isolated and identified as schaftoside (8), vicenin-2 (9), lucenin-2 (10), isovitexin 2"-O-rhamnoside (11), cerarvensin 2"-O-rhamnoside (12), vitexin 2"-O-rhamnoside (13), isoorientin 2"-O-rhamnoside (15), orientin 2"-O-rhamnoside (16) and saponarin (17). In addition, gallic acid (2), the phenol C-glycosides bergenin (3) and 11-O-galloylbergenin (4), three flavonol 3-O-rhamnosides and a new C-glycosylflavone identified as mollupentin 2"-O-rhamnoside (14) were obtained from the leaves of Allophyllus edulis var. edulis. Their structures were elucidated on the basis of chemical and spectral data. For the first time the C-glycosylflavones were found to have remarkable anti-hepatotoxic activities against CCl4 and galactosamine cytotoxicity in primary cultured rat hepatocytes. Structure-activity relationships are discussed.

Animals↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗