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Biomedical subjects

E Weber

Publications and source records attributed to E Weber.

At least 307 records · Page 17Linked to original sources

Distribution pattern of metorphamide compared with other opioid peptides from proenkephalin and prodynorphin in the bovine brain.

Metorphamide is a [Met]-enkephalin-containing opioid octapeptide with a C-terminal alpha-amide group. It is derived from proenkephalin and is, so far, the only endogenous opioid peptide with a particularly high affinity for mu opioid (morphine) receptors, a somewhat lesser affinity for kappa opioid receptors, and a relatively low affinity for delta opioid receptors. The concentrations of metorphamide in the bovine caudate nucleus, the hypothalamus, the spinal cord, and the neurointermediate pituitary were determined by radioimmunoassay and chromatography separation procedures. Metorphamide concentrations were compared with the concentrations of eight other opioid peptides from proenkephalin and prodynorphin in identical extracts. The other opioid peptides were [Met]-enkephalyl-Arg6-Phe7 and [Met]-enkephalyl-Arg6-Gly7-Leu8 from proenkephalin; alpha-neoendorphin, beta-neoendorphin, dynorphin A(1-8), dynorphin A(1-17), and dynorphin B from prodynorphin; and [Leu]-enkephalin, which can be derived from either precursor. All opioid peptides were present in all four bovine neural tissues investigated. Metorphamide concentrations were lower than the concentrations of the other proenkephalin-derived opioid peptides. They were, however, similar to the concentrations of the prodynorphin-derived opioid peptides in the same tissues. Marked differences in the relative ratios of the opioids derived from prodynorphin across brain regions were observed, a finding suggesting differential posttranslational processing. Differences in the ratios of the proenkephalin-derived opioids across brain regions were less pronounced. The results from this study together with previous findings on metorphamide's mu opioid receptor binding and bioactivities suggest that the amounts of metorphamide in the bovine brain are sufficient to make this peptide a candidate for a physiologically significant endogenous mu opioid receptor ligand.

Animals↗

Immunohistochemical demonstration of proGnRH and GnRH in the preoptic-basal hypothalamus of the primate.

An antiserum (ARK-1) specific to the gonadotropin-releasing hormone precursor (proGnRH) was produced by immunizing with a synthetic peptide (proGnRH 6-16; Gly-Leu-Arg-Pro-Gly-Gly-Lys-Arg-Asp-Ala-Glu) which bridges the proteolytic cleavage site of proGnRH. When used in the radioimmunoassay, ARK-1 bound 25% of the iodinated 5-16 fragment at a 1:30,000 dilution with a sensitivity of 1 pg/tube. Using immunohistochemical techniques, we observed that in serial and the same sections through the preoptic-basal hypothalamus (POA-BH), the precursor molecule was primarily present in the cell soma, whereas GnRH was found in the cell soma, nerve fibers, and terminals of the same neurons. These data indicate that the processing of proGnRH to biologically active peptides (e.g., GnRH) in the rhesus macaque and the baboon POA-BH primarily occurs in the cell soma.

Animals↗

Chronic ursodeoxycholic acid- and chenodeoxycholic acid-feeding-induced changes of colon mucosal cell proliferation in rats.

Hyperproliferation has been suggested to play a major role in bile acid-dependent colorectal tumor promotion. Effects of chronic feeding of chenodeoxycholic acid (CDC) and ursodeoxycholic acid (UDC) were tested on cell proliferation in the colon of male noninbred Wistar rats. By use of a dynamic method measuring actual rates of cell production, proliferation was modulated by both bile acids only in the proximal part of the colon. UDC feeding produced mild hyperproliferation of basal crypt cells (cell position 5-8: 7.6 +/- 2.0 vs. 3.5 +/- 1.3 cells/1,000 cells/hr--P less than .05; cell position 9-12: 18.1 +/- 10.7 vs. 10.3 +/- 2.9--P less than .05; cell position 13-16: 18.1 +/- 8.9 vs. 9.1 +/- 2.3--P less than .05). This finding reflected a characteristic compensatory response to superficial cell damage. However, CDC application did not effect cell regeneration in this crypt area but led to a striking drop of cell renewal in higher crypt cell positions (positions greater than or equal to 17), where no proliferation was detectable. These data suggest that CDC exerts its tumor-promoting effect by other means than hyperproliferation.

Animals↗

[Effect of immunomodulation following allogeneic blood transfusion on tumor neogenesis and growth--experimental studies in rats].

The influence of allogeneic blood transfusions (BT) on experimental tumor growth was investigated in three syngeneic, one allogeneic and one autochthonous tumor model in the rat. Con A induced T-cell response, relative distribution of lymphocyte subsets using flow cytometry and cytotoxic antibodies were determined. No differences in take rate, induction time, incidence and growth rate of tumors were observed in the different models. A significant decrease of cell-mediated immunity and a significant increase of peripheral Ia-positive cells could be observed. The relative distribution of T-cell subsets showed no differences between BT-groups and controls.

Adenocarcinoma↗

Effects of mitoxantrone and doxorubicin on energy metabolism of the rat heart.

In animal models anthracyclines and anthracenediones show similar antineoplastic activity but somewhat different cardiotoxicity. The effects of doxorubicin and the free base of mitoxantrone (NSC-279836) on the energy metabolism of the rat heart were compared. Both compounds not only reduced oxygen consumption in heart mitochondria ex vivo, but also uncoupled oxidative phosphorylation, inhibited creatine phosphate kinase, and damaged the semipermeability of the inner mitochondrial membrane (measured as creatine influx). The effects on the myocyte membrane activities, calcium transport, and Na/K, Mg, and Ca ATPases were slightly different for the two compounds. Cardiotoxicity of the two compounds may have its origin in their interference with heart cell energy metabolism.

Animals↗

Chromosomal mapping of the uracil permease gene of Saccharomyces cerevisiae.

The gene FUR4, coding for the uracil permease in Saccharomyces cerevisiae, was mapped on chromosome II, at a distance of 7.8 cM from the centromere on the right arm of the chromosome. In a first step, we used the chromosome loss mapping method developed by Falco and Botstein (1983) to determine on which chromosome the gene mapped. After the observation that FUR4 was closely linked to GAL10, one of the three genes forming the gal cluster (Bassel and Mortimer 1971), we could determine precisely the position of the gene on chromosome II.

Chromosome Mapping↗

Astrocytes as antigen-presenting cells. Part II: Unlike H-2K-dependent cytotoxic T cells, H-2Ia-restricted T cells are only stimulated in the presence of interferon-gamma.

Various studies strongly suggest that astrocytes are potent immune-regulating cells. They can be activated to release prostaglandin E, interleukin-1- and interleukin-3-like factors. Cocultivation of antigen-specific T cell lines and astrocytes results in induction of Ia on astrocytes and antigen-specific proliferation of T cells. In the current study, astrocytes were found to be incapable of serving as stimulator cells when unprimed T lymphocytes were used as responders in syngeneic or allogeneic lymphocyte reactions. However, when interferon-gamma (IFN-gamma) was added, astrocytes became Ia positive and potent stimulators in both syngeneic or allogeneic lymphocyte responses. In the presence of IFN-gamma, astrocytes presented antigens to Ia-restricted T hybridoma cells; in contrast hapten was presented to Kb-restricted cytotoxic cloned T cells by astrocytes in the absence of IFN-gamma. Thus, cultured astrocytes do function directly as accessory cells in class I antigen-dependent T cell activation, whereas Ia induction by IFN-gamma is necessary to enable them to present antigen to class II antigen-restricted T cells.

Animals↗

On the role of astrocytes in polyclonal T cell activation.

Murine astrocytes have been identified to possess accessory cell functions, which are thought to be regulated by the inducible expression of surface Ia molecules. The accessory cell functions include the induction of syngeneic and allogeneic T lymphocyte responses, the cytotoxic T cell activation towards haptens and the antigen-induced stimulation of helper T cell lines. In this report, astrocytes initially being Ia antigen-negative cells were found to restore the phytohaemagglutinin (PHA) response of mouse lymph node cells depleted of accessory cells by treatment with leucin methyl ester (Leu ME). Antisera against Ia determinants did not inhibit the PHA response or the release of interleukin-1 (IL-1) by activated astrocytes. Thus, the presence of Ia antigens is not required for mitogen-induced polyclonal T cell activation. In addition to IL-1 release, astrocytes may favour cell-cell contacts necessary for mitogen-induced polyclonal T cell response.

Animals↗

1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels sigma-type receptors for psychotomimetic opiates and antipsychotic drugs.

Brain sigma-type receptors are thought to mediate hallucinogenic effects of certain benzomorphan opiates in humans. The biochemical characterization of sigma receptors has been difficult because of the lack of potent and selective ligands. We report here the synthesis and characterization of a tritiated, symmetrically substituted guanidine derivative, 1,3-di(2-[5-3H]tolyl)guanidine ([3H]Tol2Gdn), that binds with high affinity to a single population of binding sites in guinea pig brain membrane preparations. The [3H]Tol2Gdn binding site displays stereoselectivity for dextrorotatory optical isomers of benzomorphan opiates known to have sigma-type behavioral effects. Furthermore, the [3H]Tol2Gdn binding site has a high affinity for haloperidol and for phenothiazine antipsychotics, which have antihallucinatory properties in humans. The drug-selectivity profile of [3H]Tol2Gdn binding closely correlates with the drug-selectivity profile of tritiated (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [+)-[3H]3-PPP) binding to guinea pig brain membrane receptors. (+)-[3H]3-PPP has been proposed to be a selective sigma-receptor ligand [Largent, B. L., Gundlach, A. L. & Snyder, S. H. (1984) Proc. Natl. Acad. Sci. USA 82, 4983-4987]. Receptor autoradiography using [3H]Tol2Gdn on slide-mounted rat and guinea pig brain sections reveals a heterogeneous distribution pattern of enriched binding in limbic and sensorimotor structures of the brain. These results indicate that [3H]Tol2Gdn is a selective ligand for the sigma-site. Availability of this sigma-receptor probe should greatly facilitate the physiological, biochemical, and pharmacological characterization of sigma receptors in brain.

Animals↗

Isolation and structure of a C-terminally amidated nonopioid peptide, amidorphin-(8-26), from bovine striatum: a major product of proenkephalin in brain but not in adrenal medulla.

We have isolated and sequenced a C-terminally amidated peptide from bovine striatum. The peptide was purified to homogeneity by adsorption to XAD-2 resins and four different HPLC steps. Amino acid composition analysis and gas-phase sequence analysis revealed identity of this peptide with residues 8-26 of the proenkephalin-derived opioid peptide amidorphin, which we have recently isolated from bovine adrenal medulla. C-terminal amidation of amidorphin-(8-26) from bovine striatum was demonstrated by its stability to carboxypeptidase A digestion and full crossreactivity in a radioimmunoassay that required the C-terminal amide group as part of the recognition site. The nonopioid peptide amidorphin-(8-26), which lacks the N-terminal [Met]enkephalin sequence of amidorphin, is a major product of the opioid peptide precursor proenkephalin in the brain. In the adrenal medulla, however, where amidorphin occurs in remarkably high concentrations, amidorphin-(8-26) could not be detected. This is indicative of differential post-translational processing of proenkephalin in different tissues. In the brain, as opposed to the adrenal medulla, amidorphin is further processed at the typical cleavage signals of two basic residues, giving rise to the nonopioid peptide amidorphin-(8-26) and, possibly, to the opioid peptide [Met]enkephalin. Thus, proenkephalin in the brain might be considered as a precursor in which an opioid peptide is linked with a nonopioid peptide of possibly different biological function.

Adrenal Medulla↗

Immunoreactive dynorphin B in sacral primary afferent fibers of the cat.

Immunocytochemical analysis of the distribution of dynorphin B terminals in the sacral spinal cord of the cat revealed a pattern of staining very similar to that produced with antisera directed against the primary afferent derived, putative neurotransmitter, vasoactive intestinal polypeptide. Labeled axons and terminals were concentrated in lamina I and V and there was dense fiber staining in the tract of Lissauer. Of particular interest was the presence of immunoreactive axons in attached dorsal rootlets. To specifically focus on the possibility that some of the sacral primary afferent fibers are dynorphin-immunoreactive, we first tried to increase perikaryal labeling in the sacral dorsal root ganglia by topical treatment with colchicine. This did not produce immunoreactive labeling of cell bodies in the ganglia. Unilateral multiple dorsal rhizotomy (L5 to coccygeal 1), however, significantly decreased the staining of dynorphin-immunoreactive axons and terminals in the tract of Lissauer and in the dorsal horn of sacral segments ipsilateral to the deafferentation. No changes were detected in the lumbar cord. Finally, radioimmunoassay of caudal lumbar and sacral dorsal root ganglia was performed. Measurable immunoreactivity was found in all ganglia assayed, but, consistent with the histochemical analysis, sacral ganglia contained the highest concentration of immunoreactive dynorphin B. These data indicate that a significant component of the sacral spinal cord dynorphin terminal immunoreactivity derives from primary afferent fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunohistochemical evidence for subpopulations of dynorphinergic neurons.

Biochemical studies have shown that the dynorphin precursor can generate at least seven opioid peptides. We report here a study of dynorphin products analyzed on adjacent semithin sections of rat brain, showing evidence for differential peptide localization among magnocellular neurons. In the oxytocinergic nucleus of the anterior commissure, staining was strong for dynorphin B but very weak for other prodynorphin markers; in the supraoptic nucleus, a discrete subset of dynorphin neurons were positive for leu-enkephalin.

Animals↗

Co-cultivation of endothelial and smooth muscle cells on opposite sides of a porous membrane.

A co-culture system is here proposed that mimics the topographical situation of the vessel wall in which endothelial cells are separated by a fenestrated elastic lamina from smooth muscle cells. Bovine aortic endothelial cells were grown on one side of a thin microporous membrane and smooth muscle cells were cultivated on the other side. The microporous membrane was inserted in a special frame so that a two-compartment system was created. The membrane may act like the fenestrated internal elastic lamina of arteries in allowing interactions and fluid exchanges between the two cell types through its pores. Membranes were examined both by transmission and scanning electron microscopy to evaluate the morphology of both cell types.

Animals↗

[Compulsory commitment of psychiatric patients from the viewpoint of physicians and judges--exemplified by the use of the psychiatric law of North Rhine and Westphalia].

For several years now a working team of judges and physicians has been tackling the questions involved in the compulsory hospitalisation of mentally diseased patients. In the course of this teamwork the deficiencies and drawbacks of hospitalisation legislation have become glaringly evident. The problems of hospitalisation by law and under the legislation practised by Guardianship Courts, are compared by juxtaposition. It will be necessary to employ the principles of family law if the principle of care and need of treatment should receive priority over that of the potential danger to society (which dominates present hospitalisation legislation). However, before any adequate measures can be taken, it will be absolutely necessary to effect essential changes in the "law on care and protection of mentally ill patients" that has been in force in North Rhine Westphalia since the end of 1969. It will also be necessary to change the practices observed in enforcing this law.

Commitment of Persons with Psychiatric Disorders↗

Pharmacokinetics of erythromycin in patients with different degrees of renal impairment.

The kinetics of erythromycin (E.) was studied in 16 patients with different degrees of impairment of renal function after a single intravenous dose. Renal clearance of E. was found to be significantly correlated to the creatinine clearance. Total recovery in urine did not exceed 7.5%. As expected from the small fraction excreted via the kidneys, the elimination half-life and the total clearance of E. did not depend on renal function. We conclude that impairment of renal function does not justify a dose adjustment of E. Hearing acuity should, however, be monitored during treatment since transient deafness predominantly in patients with renal failure has been reported by various authors.

Adult↗

More than additive toxicity of the combination of 1-methyl-1-nitrosourea plus 1,3-bis(2-chloroethyl)-1-nitrosourea in the rat.

The combination toxicity index of 1-methyl-1-nitrosourea plus 1,3-bis (2-chloroethyl)-1-nitrosourea determined in the rat was 0.32. This overadditive combination toxicity appears mainly to be due to severe damage of the intestinal mucosa as diagnosed by histological examination and to damage of pluripotent stem cells in the bone marrow as could be assessed by the spleen colony technique. The molar ratio of 1-methyl-1-nitrosourea to 1,3-bis(2-chloroethyl)-1-nitrosourea resulting in maximum mortality was about 6. Concomitantly measured DNA interstrand cross-linking in bone marrow cells revealed a slight increase in DNA interstrand cross-linking following both drugs compared to 1, 3-bis(2-chloroethyl)-1-nitrosourea alone.

Animals↗