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Biomedical subjects

G Beck

Publications and source records attributed to G Beck.

At least 73 records · Page 4Linked to original sources
PubMed1995

Nonpeptide endothelin receptor antagonists: IV. Identification of receptors in rabbit colonic mucosa and smooth muscle and correlation with physiological effects.

Endothelin (ET) has been previously demonstrated to be a potent intestinal secretory stimuli and to elicit intestinal smooth muscle contractions. In rat distal colon, the ETA receptor antagonist cyclo[D-Asp-L-Pro-D-Val-L-Leu-D-Trp] abolishes the changes in ion transport (as measured by short-circuit current) elicited by ET-1. In this study, effects of ET-1, sarafotoxin 6c and "big" ET in the absence and presence of the endothelin receptor antagonists cyclo [D-Asp-L-Pro-D-Val-L-Leu-D-Trp] and (+/-)-3-[2-(carboxymethoxy)-4-methoxyphenyl]-1-[3,4- (methylenedioxy)phenyl]-5-(prop-1-yloxy)indan-2-carboxylic acid on ion transport in rabbit distal colon were assessed through measurement of short-circuit current changes in segments of muscle-stripped mucosa in Ussing chambers. In addition, changes in smooth muscle contraction in response to acetylcholine, ET-1, ET-3 and sarafotoxin 6c in the absence and presence of (+/-)-3-[2-(carboxymethoxy)-4-methoxyphenyl]-1-[3,4- (methylenedioxy)phenyl]-5-(prop-1-yloxy)indan-2-carboxylic acid and of cyclo [D-Asp-L-Pro-D-Val-L-Leu-D-Trp] were measured in mucosa-free preparations oriented along their longitudinal axes. Receptor binding studies with mucosal or smooth muscle homogenates were conducted with [125I]ET-1, with [125I]ET-3 and with [125I]Tyr13Suc-[Glu9,Ala11,15]-endothelin-1(8-21 ) to identify the subtypes of ET receptors present in these preparations. From studies with rabbit colonic mucosa, both binding studies and measurement of short-circuit current confirm that the ETB receptor subtype is the predominant subtype and is responsible for the changes observed in ion transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

[Photodynamic therapy of small adenocarcinomas with methylene blue].

Photodynamic therapy (PDT) is a new method in the treatment of small/early malignancies. It is based on the interaction of a photosensitiser, light and cellular oxygen. A new therapeutic concept with locally applied 1% of methylene blue into the tumour and subsequent radiation (argon laser pumped dye laser, 665 nm, 100 mW/cm2, 100 J/cm2) was first tested in xeno-transplanted carcinomas and then clinically applied. The animal experiments showed a tumour volume reduction of 1:12, as compared to a control group, two weeks after the first PDT-application. After the second PDT-treatment 6 out of 10 tumours were destroyed. Four carcinomas showed inhibited growth after the treatment. The method was clinically applied in 3 patients with local tumour recurrence in the area of the anastomosis after oesophagus resection. 72 hours after PDT-treatment 4-5 mm tumour necrosis could be proven experimentally. PDT was repeated at the same site within 2 weeks. There were no experimental or clinical complications during or after PDT. The treated tumour areas showed no local tumour growth within 6 months after PDT-treatment.

Adenocarcinoma↗
PubMed1994

Determinants of hospital stay after modified radical mastectomy.

The most expeditious way of reducing surgical costs is through reducing hospital stay. Multivariate analysis was used to identify potentially alterable factors affecting postoperative hospital stay for 73 consecutive patients undergoing modified radical mastectomy by 6 surgeons during a 12-month period. Stepwise logistic regression was used to identify independently significant preoperative variables associated with hospital stays equal to or greater than the median of 5 days. Intraoperative techniques and postoperative management were then evaluated using Cox proportional hazards model, with length of stay as the dependent variable after consideration for the significant independent preoperative factors. Age, history of heart disease, hypertension, diabetes, obesity, and American Society of Anesthesiologists (ASA) risk were significantly associated with prolonged stay (more than 4 days) in univariate analysis. Only age (P < 0.001) and cardiac history (P = 0.013) were significant independent predictors of hospital stay in multivariate analysis. After consideration for age and cardiac history, the only significant intraoperative or postoperative factor associated with hospital stay was the use of dressings incorporating Steri-Strips. This study suggests that the attribution of the reduction in hospital stay to discharge with drains in place is due to numerous factors, only one of which is the willingness to send patients home with the drains.

Age Factors↗
PubMed1994

Cortisol and beta-endorphin responses to sleep deprivation in major depression--the hyperarousal theories of sleep deprivation.

To test theories that response to sleep deprivation in depression is the result of either stress reactions or down-regulation of hyperarousal, the early morning cortisol and beta-endorphin levels of depressed sleep deprivation responders and nonresponders before and after sleep deprivation were compared (areas under the curve of 8 blood samples between 7:30 and 10 a.m.). The beta-endorphin response was significantly different in responders and nonresponders, whereas all other comparisons remained nonsignificant. The results do not support theories that sleep deprivation acts as a stressor, but are not contradictory to the hyperarousal hypothesis of sleep deprivation.

Adult↗
PubMed1993

Biotransformation of 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-1-propynyl-estra-4,9-dien-3-one (RU486) in rat hepatoma variants.

Metabolism of the synthetic steroid 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-1-propynyl-estra-4,9-dien-3-one (RU486) occurs in the dedifferentiated S-H56-125 variant of Reuber hepatoma. Considering that rat liver cytochrome P450 (P450) monooxygenases are engaged in different oxidative steps of the metabolism of RU486, the influence of several prototype P450 inducers was investigated. The data obtained by treating H56 and S-H56-125 hepatoma cells with different P450 inducers (dexamethasone (DEX), benzanthracene, phenobarbital) or with a specific P450 inhibitor, troleandomycin, led us to conclude that CYP3A is involved in the hydroxylation of RU486. This form is induced by DEX independently of the availability of the canonical glucocorticoid receptor.

Animals↗
PubMed1993

Antiproliferative action of the steroid RU486 in cultured human lymphoma cells.

The antiproliferative properties of the synthetic steroid RU486 on the human lymphoma cell line Daudi are described. In suspension cultures, RU486 (10 microM) caused a time dose and cell density dependent reduction of cell proliferation. This effect was reversed within 48 h of withdrawal of RU486 from the growth medium. High concentrations of foetal calf serum can mask the inhibitory effect. In semi-solid cultures RU486 also impaired cell proliferation. Thus RU486 was able to suppress in this tumor cell line the expression of some properties frequently associated with the transformed status of the cells.

Cell Count↗
PubMed1993

Invertebrate cytokines. III: Invertebrate interleukin-1-like molecules stimulate phagocytosis by tunicate and echinoderm cells.

Phagocytosis is the predominant defense mechanism of invertebrates. Here we show that phagocytosis by echinoderm bladder amoebocytes and tunicate granular amoebocytes can be enhanced by invertebrate interleukin-1-like molecules. As little as 5 ng/ml of invertebrate interleukin-1 produced a significant stimulation of echinoderm and tunicate amoebocyte phagocytosis. Stimulation of phagocytosis by echinoderm interleukin-1-like molecules was inhibited by antisera to vertebrate interleukin-1. Invertebrate interleukin-1 also acted as an opsonin when preincubated with erythrocytes or yeast. In addition, the cellular mechanisms of invertebrate phagocytosis were studied using pharmacologic agents to inhibit echinoderm amoebocyte phagocytosis. The energy requirements and involvement of cellular cytoskeletal elements in phagocytosis by bladder amoebocytes were similar to those of mammalian macrophages. These results demonstrate a role for interleukin-1 in invertebrate host defense mechanisms.

Animals↗
PubMed1993

Hypothermia induced by hyperbaric oxygen is not blocked by serotonin antagonists.

Exposure to HBO causes hypothermia, bradycardia, head weaving, resting tremor, piloerection, and straub tail in rats. These physiological and behavioral responses can also be evoked by selective activation of serotonin1A (5-HT1A) receptors. The purpose of the current study was to determine if hypothermia caused by HBO is due to increased activation of 5-HT1A receptors. The levels of brain biogenic amines were measured in brain regions of Sprague-Dawley (SD) rats exposed to HBO. Exposure to HBO caused an increase in the levels of 5-hydroxyindoleacetic acid (5-HIAA) in the striatum (92%, p < 0.05) and occipital-temporal cortex (116%, p < 0.05), but not in other brain regions. Exposure to HBO did not change the levels of tryptophan, serotonin (5-HT), other biogenic amines, or their metabolites. It is hypothesized that the Fawn Hood (FH) rat, which is reported to be resistant to hypothermia induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), has an abnormality of 5-HT1A receptor activity. Although the FH rat was more resistant to hypothermia induced by HBO than the SD rat, we were not able to confirm that this rat was resistant to hypothermia induced by 8-OH-DPAT. The 5-HT receptor antagonists, 1-(1H-Indol-4-yloxy)-3-[(1-methylethyl)amino]-2-propanol (Pindolol), 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide (NAN-190), and methysergide, did not block hypothermia induced by HBO in SD rats. A series of control experiments were used to confirm that the antagonists blocked hypothermia induced by serotonin agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗
PubMed1993

Binding studies of RU486 in different Reuber hepatoma variants.

The synthetic steroid RU486, which displays antiprogestin and antiglucocorticoid properties in different systems, inhibits cell growth in dexamethasone-sensitive H56 cells containing glucocorticoid receptors, as well as in dexamethasone-resistant S-H56-125 cells displaying a very low level of dexamethasone binding. In order to better understand the mechanism of the antiproliferative effect, the binding of RU486 to these hepatoma cells was examined. Results revealed the presence of two different kinds of binding sites for RU486 in dexamethasone-sensitive H56 cells whereas only one type of site was detected in the dexamethasone-resistant cells. These peculiar sites were also recognized by cortivazol during competition experiments. Thus, it seems that S-H56-125 cells contain an altered glucocorticoid receptor that binds RU486 and cortivazol but virtually not dexamethasone. The ability of RU486 to inhibit the growth of dexamethasone-resistant cells suggests this steroid may be used to treat tumor cells that develop glucocorticoid resistance after long-term treatment.

Animals↗
PubMed1992

Mechanism for the recruitment of macrophages to cancer site. In vivo concentration gradient of monocyte chemotactic activity.

BACKGROUND: Tumor stroma is characterized by the development of new blood vessels, an inflammatory cell infiltration, and a fibrotic reaction. The inflammatory component of tumor stroma plays an important role in the modulation of tumor expansion. In this respect, macrophages constitute a major part of the inflammatory cell infiltration and can exert cytotoxic activity against tumor cells. The accumulation of macrophages in the vicinity of the tumor suggests their recruitment from circulating blood monocytes through the local release of chemotactic factors for monocytes. METHODS: To detect the existence of a concentration gradient of monocyte chemotactic activity (MCA) between the tumor vicinity and blood vessels, malignant pleural effusions defined by the local presence of cancer cells were evaluated for quantification of MCA. RESULTS: Unlike nonmalignant pleural effusions, malignant pleural effusions were characterized by the presence of increased levels of MCA, and in lung adenocarcinoma (a cancer with high inflammatory cell infiltration), pleural levels of MCA were significantly greater than in small cell lung carcinoma (a cancer with low inflammatory cell reaction). An MCA concentration gradient between pleural fluid and plasma was present in malignant effusions because pleural MCA levels in all cancer types were significantly greater than MCA levels in the plasma of the same patients. CONCLUSIONS: Thus, an increased local level of MCA is a feature of cancers with high inflammatory cell infiltration, and the presence of an in vivo concentration gradient of MCA suggests the direct role of this biologic activity in recruiting blood monocytes to the cancer site.

Adenocarcinoma↗
PubMed1992

How the potency of the steroid RU486 is related to P450 activities induced by dexamethasone and phenobarbital in rat hepatoma cells.

In a previous work on rat liver microsomes, we demonstrated that cytochrome P450 isozymes (P450) are engaged in the metabolism of RU486. In order to study the underlying mechanism at the molecular level, our investigations were shifted to a simplified system of cultured hepatoma cells which present a dissociation in the expression of distinct P450 coding genes. Our results show that Fao cells represent a convenient model to study both: (i) the degradation of RU486. Forms IIB1,2 and IIC7, which are present in Fao cells, may contribute to the demethylation of the molecule. Form IIIA, which has not been detected in Fao cells, is probably responsible for its oxidation in the liver; (ii) the effect of RU486 on the expression of P450 enzymes. Unlike other steroids (dexamethasone and pregnenolone 16 alpha-carbonitrile), RU486 does not induce P450 activity but inhibits the inducing activity of other agents such as dexamethasone and also phenobarbital. These findings may be important for the therapeutic use of RU486 since its inhibitory effect on P450 activity may be at the origin of drug interactions by modifying the endogenous hormonal status.

Aminopyrine↗
PubMed1992

Purification and immunological characterization of a major low-molecular-weight lipoprotein from Borrelia burgdorferi.

Borrelia burgdorferi resembles gram-negative bacteria in having both cellular and outer membranes. We previously showed that a lipopolysaccharide (LPS)-like material could be extracted from B. burgdorferi with phenol-chloroform-petroleum ether (PCP). The PCP extract of B. burgdorferi exhibited biological activity in several in vitro assays (e.g., mitogenicity, pyrogenicity, and cytokine release). These activities suggested the presence of endotoxin. The PCP extract of B. burgdorferi, however, also contained a small amount of protein. Preliminary studies showed that monoclonal antibody prepared against this protein inhibited the mitogenic activity of the PCP extract toward murine spleen cells. The current study was therefore undertaken to characterize this protein and to establish methods for its separation from the LPS. The PCP-extracted protein consisted of a single, low-molecular-weight lipoprotein (apparent M(r), 10,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) (SDS-PAGE). By protein analysis, it accounted for 2% of the dry weight of defatted cells, thus making it a major constituent of the spirochete. It was purified from the LPS by initial extraction into 10% Triton X-100 followed by immunoaffinity chromatography in the presence of detergent. On removal of the LPS, the purified lipoprotein formed aggregates stable to SDS-PAGE which were detectable on Western blots (immunoblots) probed with either the monoclonal antibody or polyclonal antiserum. From a plot of the aggregate molecular weight versus aggregate size, a monomer molecular weight of 7,500 was obtained. Indirect immunofluorescence with the monoclonal antibody showed that the lipoprotein was exposed at the surface of the spirochete in only a small percentage of cells. The lipoprotein was present in several strains of B. burgdorferi but absent in other Borrelia spp., treponemes, and gram-negative human pathogens, indicating species specificity.

Animals↗
PubMed1992

Invertebrate cytokines II: release of interleukin-1-like molecules from tunicate hemocytes stimulated with zymosan.

Conditioned media and cell extracts from tunicate hemocytes that had been cultured with a variety of antigenic stimulants were tested for interleukin-1 (IL-1)-like activity. Media conditioned by hemocytes stimulated with zymosan significantly increased the proliferative and phagocytic activities of tunicate hemocytes. SDS-PAGE indicated that these biological activities were associated with the adaptive release of tunicate IL1-like (tunicate IL-1) molecules by stimulated hemocytes. The data suggest that tunicate IL1 molecules are expressed in response to selected antigenic stimuli. Such responses may form the basis for nonclonal, inducible immune reactions among phylogenetically primitive animals.

Animals↗
PubMed1992

Role of the physiochemical properties of mucus in the protection of the respiratory epithelium.

The respiratory mucus is a very complex biological material, which possesses both flow and deformation rheological properties, characterized by non-linear and time-dependent viscoelasticity and physical properties of adhesiveness and wettability. Viscosity and elasticity are directly involved in the transport capacity of mucus, whereas wettability and adhesiveness contribute to the optimal interface properties between the mucus and the epithelial surface. Optimal conditions for the protective and lubricant properties of respiratory mucus are represented by high wettability, and adhesiveness high enough not to induce flow of mucus in the respiratory bronchioles under gravity but low enough to mobilize mucus by airflow during coughing. An intermediate viscoelasticity is also required for an optimal mucociliary transport. Different biochemical constituents such as glycoproteins, proteins, proteoglycans and lipids are involved in the gel properties of respiratory mucus. During bronchial infection and particularly in cystic fibrosis, the loss of water and the increase in macromolecules result in a marked increase in viscosity and adhesiveness responsible for the mucus transport impairment. The various lipids present in mucus contribute differently to the physicochemical properties. Surface-active phospholipids, such as phosphatidylcholine and phosphatidylglycerol improve the wettability of mucus, whereas neutral lipids and glycosphyngolipids contribute to the hyperviscosity of mucus during infection. Phospholipids and associated mucins are also implicated in the interaction between bacteria and epithelial cells. Therefore, the respiratory mucus needs appropriate physicochemical properties for the protection, hydration and lubrication of the underlying airway epithelium.

Adhesiveness↗
PubMed1991

Invertebrate cytokines: tunicate cell proliferation stimulated by an interleukin 1-like molecule.

Tunicate pharyngeal cells include lymphocyte-like cells and granular amoebocytes. They are involved in the specific allogeneic and phagocytic reactions of tunicates. Little is known about their regulation or control. A tunicate interleukin 1 (IL-1)-like fraction is shown to stimulate the proliferation of these cells in vitro. This fraction, designated tunicate IL-1 beta, was isolated from tunicate hemolymph by gel filtration and chromatofocusing chromatography. Mitogenic responses to tunicate IL-1 beta were dose dependent and could be eliminated rapidly by removing tunicate IL-1 beta from culture medium. A second tunicate hemolymph fraction had no effect on tunicate cell proliferation even though it exhibited IL-1-like activity in a mouse thymocyte proliferation assay. Phytohemagglutin did not act synergistically with either fraction. These data are discussed in terms of the function and evolution of IL-1-like molecules in invertebrates.

Animals↗
PubMed1991

Activation of Epstein-Barr virus promoters by a growth-factor and a glucocorticoid.

Transforming growth factor-beta (TGF-beta) and a glucocorticosteroid, Dexamethasone (DXM), both cause transcriptional induction of Epstein-Barr virus (EBV) early antigens (EA) in Daudi lymphoma cells. The viral induction occurs through the viral promoter DR overlapping an origin of replication which is active during the lytic cycle. Each hormone requires specific regions on the DR promoter. Since these regions also mediate the action of two viral transcription factors, EB1 and R, it may be emphasized that EB1 and/or R are involved in the EA induction process by TGF-beta and by DXM.

Antigens, Viral↗