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Biomedical subjects

E Weber

Publications and source records attributed to E Weber.

At least 595 records · Page 33Linked to original sources
PubMedDate not supplied

N-(3-azidophenyl)-N-methyl-N'-([4-1H]- and [4-3H]-1-naphthyl)guanidine. A potent and selective ligand designed as a photoaffinity label for the phencyclidine site of the N-methyl-D-aspartate receptor.

A novel radiolabeled photoaffinity ligand has been synthesized for the phencyclidine (PCP) site of the N-methyl-D-aspartate (NMDA) receptor. N-(3-Azidophenyl)-N-methyl-N'-([4-3H]-1-naphthyl)guanidine (13) was prepared with a specific activity of 25 Ci/mmol by diazotization of N-(3-aminophenyl)-N-methyl-N'-([4-3H]-1-naphthyl)guanidine (12) followed by treatment with sodium azide. Guanidine 12 was obtained by catalytic tritiation of N-(4-bromo-1-naphthyl)-N'-methyl-N'-(3-nitrophenyl)guanidine (11). The nontritiated analog 5 of 13 was prepared beginning with N-methyl-N'-1-naphthyl-N-(3-nitrophenyl)guanidine (9). The guanidines 9 and 11 were prepared in moderate yield by the aluminum chloride-catalyzed reaction of N-methyl-3-nitroaniline hydrochloride with 1-naphthylcyanamide and 4-bromo-1-naphthylcyanamide, respectively. Azide 5 showed high selectivity and affinity (IC50 = 100 nM vs [3H]MK801; 3000 nM vs [3H]ditolylguanidine) for the PCP site of the NMDA receptor in guinea pig brain homogenate. Photolabeling experiments with 13, however, failed to radiolabel a significant amount of receptor polypeptide.

Affinity Labels↗
PubMedDate not supplied

Chlorinated phenyl azides as photolabeling reagents. Synthesis of an ortho,ortho'-dichlorinated arylazido PCP receptor ligand.

The enhanced photolabeling properties of chlorinated phenyl azides are demonstrated by the synthesis and photolysis of methyl 4-azido-2,3,5,6-tetrachlorobenzoate (3) and methyl 4-azido-3,5-dichlorobenzoate (4). Photolysis of azide 3 in 1 M diethylamine/cyclohexane as the trapping medium gave 34% NH-insertion product. Similar photolysis of azide 4 gave 35% NH insertion product. These results demonstrate that chlorinated phenyl azides are significantly better at undergoing NH insertion than nonhalogenated analogs and suggest that improvement of existing aryl azide-based photolabels might be achieved by introduction of chlorine atoms on either side of the azide group. As an application, 3-azido-2,4-dichloro-10,5-(iminomethano)-10,11-dihydro-5H- dibenzo[a,d]cycloheptene (19), an analog of the potent PCP receptor ligand IDDC (14), was synthesized and its affinity for the PCP receptor was determined to be 6.3 +/- 0.7 microM (IC50 against [3H]MK801).

Affinity Labels↗
PubMedDate not supplied

A dynorphinergic pathway of Leu-enkephalin production in rat substantia nigra.

The amino acid sequence of the opioid peptide Leu-enkephalin is found within several larger peptides, which are generated from the precursors proenkephalin and prodynorphin. Proenkephalin contains four copies of the sequence of Met-enkephalin, a single copy of the sequence of Leu-enkephalin and one copy each of two extended Met-enkephalin sequences. Proenkephalin contains three peptides--alpha-neo-endorphin, dynorphin A and dynorphin B--the N-terminal sequences of which are identical to that of Leu-enkephalin. There is good evidence that the large amounts of Leu-enkephalin found in the adrenal medulla are generated from the precursor proenkephalin, but as yet prodynorphin has not been shown to be processed to yield Leu-enkephalin. We show here that the relatively high levels of Leu-enkephalin found in the rat substantia nigra are supplied by striatonigral axons and generated from the precursor prodynorphin.

Animals↗
PubMedDate not supplied

Isolation and structure of a novel C-terminally amidated opioid peptide, amidorphin, from bovine adrenal medulla.

Biologically active peptide hormones and neurotransmitters have been shown to be enzymatically liberated from larger, inactive precursor molecules by tissue-specific post-translational processing, particularly at the typical cleavage signals of paired basic residues. Subsequent N-terminal or C-terminal modifications may be of importance in regulating the biological activities of these peptides. C-terminal alpha-amidation is considered to be essential for the biological function of several non-opioid peptides. Here we present the isolation and structure of a novel C-terminally amidated opioid peptide, amidorphin, from bovine adrenal medulla. Amidorphin and the recently isolated octapeptide metorphamide (adrenorphin) are the only endogenous opioid peptides in mammals known to possess a C-terminal amide group. The amino acid sequence of amidorphin corresponds to the sequence 104-129 of bovine proenkephalin A. Very high concentrations of amidorphin were detected in bovine adrenal medulla and in a further endocrinological system, the hypothalamic-neurohypophyseal axis. Amidorphin may therefore be considered to be a major gene product of the opioid peptide precursor proenkephalin A in these endocrine tissues.

Adrenal Medulla↗
PubMedDate not supplied

[Cement-free cup and cemented shaft--concept of a hybrid solution and results of a 3-to-6-year clinical experience].

Report about the Marburg Hybrid THA using a cementless cup and a cemented stem. The acetabular component consists of an hemispheric inner polyethylene cup and an outer five-layer sintered titanium wire mesh fused together. The socket is primarily anchored by one peg as well as 2 self-stabilizing titanium nails. The forged titanium alloy stems are meeting all the requirements of the latest biomechanic research. A total of 292 Hybrid THA were implanted in 273 patients from 1. 8. 1986 to 1. 1. 1989. 6 patients (2.1%) had to undergo THA exchange surgery (1 early, 3 late infections, 1 acetabular fracture after fall, 1 loosened stem). The clinical data of 62 patients (21.2%) had to be disregarded for various reasons. Thus the data of 212 (72.6%) implanted THA in 194 patients were analyzed. 204 of the analyzed THA (96.2%) judged the result of the operation as good or very good. Radiolucency at the bone-titanium-interface of the cementless cups was present in 60 of 212 cases (28.3%), in revision operations twice as often as in primary implantations. There were no signs of progression. Radiolucency at the bone-cement-interface of the cemented stems was present in 27 of 212 cases (12.8%), with radiolucencies > 1 mm only occurring in area 7 of Gruen (1979). The overall results are thus very promising and support the concept of a hybrid solution for THA.

Adult↗
PubMedDate not supplied

Biochemical mechanisms of quinidine cardiotoxicity.

"Quinidine-like action" and the synonym "membrane-stabilizing activity" are often encountered descriptions for adverse cardiac effects of drugs. Quinidine, 50 mg/kg/day, 5 days/week for 4 weeks, was found to cause disturbance of intracardiac conduction in rats. It was the purpose of this study to investigate the effect of the same dose of quinidine on biochemical activities involved in the energy metabolism of the heart. Electron transfer activities in heart mitochondria were progressively slowed down. At the same time, uncoupling of oxidative phosphorylation was observed and mitochondrial creatinephosphate kinase activity decreased. Concomitantly, mitochondria showed a progressive loss in semipermeability, manifested by an increasing creatine content. Total adenine nucleotides (especially ATP) content declined to 65% of control values to return to normal levels at the end of the 4 week treatment period. Calcium-binding activity and various ATPases (Na/K, Mg, Ca) of myocyte membranes (sarcolemma + sarcoplasmatic reticulum fraction) were also impaired by quinidine. Protein synthesis in total heart tissue and heart mitochondria, an energy-requiring process, was also moderately inhibited by quinidine. Maximal quinidine concentration in heart tissue was 0.123 microgram/g fresh weight 24 h after the last of 19 medications.

Adenine Nucleotides↗
PubMedDate not supplied

Teased-fiber technique for peripheral myelinated nerves: methodology and interpretation.

Teased-fiber technique is the best approach for studying peripheral myelinated nerve fibers in their continuity. It enables the assessment of size of myelin segments formed by Schwann cells and characterization of pathologic changes affecting the internodia, the paranodal regions, and the invested axons. Fiber teasing is performed on prestained proximodistally oriented portions of peripheral nerves. Specimens about 10 mm long are stained for 24-48 hours in Sudan black and then transferred to glycerin, where, using a pair of fine forceps and a stereomicroscope, they are separated into smaller fiber bundles from which single fibers are isolated. The work is performed on a glass slide with an adhesive surface (albuminized or "superfrost"), on which the fibers are placed in strict proximodistal orientation. Following drying in an oven, the slides are mounted with glycerin-gelatine (same as used for frozen sections). The changes, when present, can usually be recognized during the preparation, but fibers are reexamined and changes confirmed in mounted slides. Photographic reconstruction of the fibers facilitates their assessment and enables the documentation of findings. The teased-fiber technique is auxiliary to histopathology, and to limit the workload and save costs, it can be performed on only a few specimens selected for better characterization of changes recognized or suspected in tissue sections. In particular, segmental demyelination and early stages of Wallerian or secondary axonal degeneration can be recognized in teased fibers. Segmental demyelination is characterized by loss of fully myelinated segments and their replacement by newly formed short and thin segments, remyelinating the preserved axon. The early stage of secondary axonal degeneration is recognized by formation of ovoidal fiber fragments in the midinternodal region.

Animals↗
PubMedDate not supplied

Calculation of the circular dichroism of Chironomus hemoglobin in the light of the quality of its X-ray structure.

For the larval hemoglobin III of the insect Chironomus thummi thummi, the rotational strength of the B (Soret) and Q band is calculated with a monopole/monopole and a dipole/dipole approximation applied to the atomic co-ordinates of the X-ray structures at 2.5 and 1.4 A resolution. In previous calculations using the 2.5 A co-ordinates and with perturbing groups being restricted to aromatic side-chains, the dipole/dipole approximation clearly confirmed the negative sign observed by experiment. The predominant interactions were those of phenylalanine residues. Recalculation with X-ray data refined to the present limits of performance corroborates the negativity of the rotational strength, but now the most important contributions are due to the peptide bonds formerly neglected. Also for the 2.5 A coordinates it is learned that in contrast to earlier expectation the influence of the backbone in this hemoglobin is rather strong. A substantial contribution is further obtained for the perturbation by one of the propionic acid carboxylate groups of the heme. Perspectives and problems of the approach are outlined.

Amino Acids↗
PubMedDate not supplied

Induction of gastrin releasing peptide by all-trans retinoic acid in small cell lung cancer cells.

All-trans retinoic acid (RA) has been shown to inhibit cell proliferation while increasing neuroendocrine differentiation in small cell lung cancer (SCLC) cells. RA and related compounds are rapidly becoming integrated into clinical trials to prevent lung cancers and other aerodigestive neoplasms. We found that expression of gastrin releasing peptide (GRP), which can promote lung tumorigenesis in model systems, was increased by RA in SCLC cells which have functional retinoid signaling. In SCLC cells that possess functional GRP receptors, ectopic expression of RARc increased GRP expression and augmented cloning efficiency, demonstrating that these maneuvers result in biologically active GRP. SCLC cells with defects in RA pathway signaling did not efficiently induce GRP upon RA exposure. In these cells, transfection of RARs rendered the cells competent to induce GRP upon RA exposure. These data show that activation of intact retinoid signaling by RA can induce GRP, a growth factor that can act as a tumor promoter. Our findings suggest the possibility that retinoids may increase, rather than decrease, lung cancer risks in some individuals.

Carcinoma, Small Cell↗
PubMedDate not supplied

[Practical approach according to the Federal Infection Legislation in meningococcal diseases in community facilities from the viewpoint of Public Health physicians in Offenburg].

Within the area for which the Public Health Office Offenburg is in charge, numerous meningococcal diseases in childhood occurred in 1988. As a result there of, a new strategy for the control of meningococcal diseases in day-care centers has been developed. In this respect priority has been given to rapid mutual information among the persons involved together with the strict control and supervision of all contact persons. This strategy led to an acceptable compromise for all persons involved; the strategy aims at achieving scientific accuracy and legal correctness, it is transparent and reproducible, and is easily implemented from an organisational point of view.

Child↗
PubMedDate not supplied

[Cerebrovascular insufficiency and compliance with drug therapy].

Particularly elder multimorbid patients suffering from a cerebrovascular insufficiency need a long term therapy. One condition for success, however, is the regular intake of drugs by the patient. Therefore the final goal is the increase of drug-compliance. This is based on the enhancement of the knowledge of the actual drug-compliance, the subject we wanted to learn more about by empirical investigations. During one year the drug-compliance of each patient of the Special Clinic Klausenbach was tested over a period of 20 days. The results were taken by checking riboflavin fluorometrically (method according to Gundert-Remy). In this way the patients could be classified as "takers" and "non-takers". The following variables wee considered: diagnoses, marital status, age, nationality, profession, IQ, mood, subjective evaluation of success of cure and medication. since according to a pre-study foreigners show a lower rate of compliance we restricted the sample to the 892 german cure patients, 343 of whom suffered from cerebrovascular diseases. Their compliance-level was almost 50%. The results of the subgroups hardly differed. The cure patients suffering from cerebrovascular insufficiencies did not show any striking compliance behaviour: the values are far below the ideal value, however. Further multivariate statistical analyses are designed to contribute to the development of effective measures of intervention.

Aged↗
PubMedDate not supplied

Nephrotoxicity of immunosuppressants in rats: comparison of macrolides with cyclosporin.

The nephrotoxic potential of the macrolide immunosuppressants, FK506 and rapamycin, was compared with that of cyclosporin (CsA) in male Wistar rats. FK506 induced a reduction of creatinine clearance, hypomagnesemia and hyperuricemia as previously described for CsA. In contrast, equidosed rapamycin did not alter the glomerular filtration rate. FK506 caused proximal tubular epithelial changes consisting of atrophy, vacuolization, inclusion bodies, microcalcification and focal mononuclear interstitial infiltrate as described for CsA. The most striking alteration was hypertrophy of the juxtaglomerular apparatus (JGA). The percentage of renin-containing JGA and the extent of renin immunoreactivity along afferent vessels were significantly increased in FK506- and CsA-treated rats. By contrast, no renal morphologic lesions were found in rapamycin-treated animals. Renal cortical extracts contained abundant cyclophilin and FK506-binding protein (FKBP), the main intracytoplasmic receptors for CsA and FK506, respectively. Furthermore, we demonstrated that receptor bound CsA and FK506, but not rapamycin, formed complexes with the phosphatase calcineurin, as shown previously for lymphocytes. Thus, it is hypothesized that both the immunosuppressive and toxic effects of FK506 and CsA, but not of rapamycin, are mediated through an immunophilin-drug-calcineurin complex. The renal substrate of calcineurin, which mediates renal vasoconstriction is yet to be identified.

Amino Acid Isomerases↗