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Biomedical subjects

H Wagner

Publications and source records attributed to H Wagner.

At least 325 records · Page 18Linked to original sources
PubMed1993

Loco-regional management of early cancer of the breast.

Early detection of breast cancer and its treatment with breast conservation therapy (BCT) are major components of a strategy aimed at improving therapeutic outcome by treating disease earlier in its course. In this paper, we review the indications and contraindications for BCT, discuss principles of integrating the required diagnostic and therapeutic modalities, and present several areas of current controversy that pose the opportunity for appropriate clinical trials.

Breast Neoplasms↗
PubMed1993

Rational integration of radiation and chemotherapy in patients with unresectable stage IIIA or IIIB NSCLC. Results from the Lung Cancer Study Group, Eastern Cooperative Oncology Group, and Radiation Therapy Oncology Group.

About 40 percent of all patients diagnosed with non-small-cell lung cancer (NSCLC) have locally advanced stage IIIA or IIIB disease. Such disease is at the borderline of anatomic resectability and associated with poor survival prospects with any present therapy. The Lung Cancer Study Group, Eastern Cooperative Oncology Group, and Radiation Therapy Oncology Group, among other North American clinical cooperative groups, have integrated radiation and chemotherapy in an attempt to prolong survival and, in some cases, cure patients with unresectable NSCLC. These two modalities have been given sequentially, concurrently, and in an alternating fashion with varying degrees of success. Trials employing cisplatin-containing chemotherapy have produced more positive results than those using other regimens, although this is not invariably so. Clearly, better treatments are needed for local and systemic disease. This paper considers possible mechanisms for combining radiation and chemotherapy, reviews the status of recent and current clinical trials, and outlines some directions for future research.

Antineoplastic Agents↗
PubMed1993

Sound-localization deficits induced by lesions in the barn owl's auditory space map.

Barn owls possess a two-dimensional map of auditory space. The map appears in its final form in the external nucleus of the inferior colliculus (ICx) and is projected from there to the optic tectum (OT). To determine the role of the map in ICx or its projected version in OT in the localization of acoustic stimuli, head movements of three adult owls were recorded before and after lesioning parts of the map either in ICx or in OT. Small electrolytic lesions caused sound-localization deficits that were characterized by failures to turn, turns away from the sound source, increased response latencies, and reduced turning amplitudes. These deficits occurred at azimuths expected from the physiological data obtained at the lesion site before passing current. They extended over an azimuthal range of some 20 degrees. Thus, this is the first unambiguous demonstration, for sound localization, of a deficit covering a well circumscribed area within an auditory hemifield. Since the major lesion deficits were restricted to one hemifield, a second lesion was made in the space map of the other side of the brain in each animal. The second lesion resulted in behavioral deficits qualitatively similar to those produced by the first lesion. In total, the study is based on nine lesions, three in each owl. Two lesions were sham lesions. These and two further lesions did not produce a measurable deficit. In four of the five remaining cases, in which a behavioral deficit was observed initially, the behavioral performance recovered with time. In two cases, the deficit disappeared completely. Although improvement occurred also in the remaining two cases, prelesion response amplitudes were not reached in one case, and response latency did not reach prelesion values in the other case. Because the behavioral deficits induced by the second lesions disappeared in the same way as did the deficits induced by the first lesions, the possibility is excluded that the animals learned to respond tactically, that is, that they learned to associate "unlocatable sounds" with the lesioned side. The deficits were also not due to a generalized motor impairment, because immediately after the lesion the animals responded as they did before the lesion to stimulation from outside the well circumscribed affected region of space. The possibility is discussed that plasticity after small central (neural) injuries is maintained longer in the lifetime of an animal than plasticity after peripheral (mechanical) manipulations.

Animals↗
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

A potentialgradient-conductivity-scanner for the investigation of effects leading to buoyancy-driven convection on continuous-flow-electrophoresis.

Continuous flow electrophoresis (CFE) is a mild and high-resolving method for the separation of sensitive biomolecules like peptides and proteins. The resolution is decreased by several effects, of which density gradients are important since they lead to buoyancy-driven convection. A tool for the measurement of physical quantities that cause the separation process, a potentialgradient/conductivity-scanner has been developed. With this PC-scanner consecutive potential- and concentration profiles can be measured inside the CFE-chamber. Local current densities and local joule heat yielding density gradients are calculated from the measurement data. With the PC-scanner the influence of gravity on separations by CFE can be evaluated more easily by the knowledge of the thermal and electrical conditions inside the separation slit.

Biotechnology↗
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↗