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Biomedical subjects

H Kessler

Publications and source records attributed to H Kessler.

At least 181 records · Page 10Linked to original sources
PubMed1988

Recombinant interferon alpha-2a for treatment of herpes zoster in immunosuppressed patients with cancer.

PURPOSE: Acyclovir and high doses of intramuscular leukocyte interferon have been shown to prevent dissemination of herpes zoster in cancer patients with localized herpes zoster. With the availability of recombinant interferon, we decided to conduct a multicenter, placebo-controlled, double-blind trial of intramuscular recombinant interferon alpha-2a to assess its efficacy and safety in the treatment of localized herpes zoster in immunosuppressed patients with cancer. PATIENTS AND METHODS: Immunosuppressed cancer patients with localized herpes zoster were randomly assigned to receive placebo, 36 X 10(6) units of recombinant interferon alpha-2a per day, or 68 X 10(6) units of recombinant interferon alpha-2a per day. Due to frequent adverse effects, the 68 X 10(6) unit dose of interferon was discontinued prior to conclusion of the trial. RESULTS: Dissemination of herpes zoster occurred in 14 of the 24 patients (58 percent) who received placebo but in only four of 24 recipients (17 percent) of 36 X 10(6) units of interferon per day (p = 0.003). Adverse effects (fever, chills, headaches, gastrointestinal irritability, fatigue, and myalgias) were more common or severe in interferon-treated patients. CONCLUSION: These results suggest that interferon modifies the severity of herpes zoster in immunosuppressed patients with cancer but is associated with frequent side effects.

Adult↗
PubMed1988

Peptide conformations--49(1): synthesis and structure-activity relationships of side chain modified peptides of cyclo(-D-Pro-Phe-Thr-Lys-Trp-Phe.).

Cyclic hexapeptide analogues representing the modified retro sequence of the amino acid residues 7-11 of natural somatostatin are known to protect liver cells from phalloidin poisoning. To determine the influence of steric, lipophilic, and charge effects on (a) the conformation of the backbone and the aromatic side chains and (b) the biological response, the side chains of Phe2, Lys4, and Phe6 of cyclo(-D-Pro1-Phe2-Thr3-Lys(Z)4-Trp5-Phe6-), 1a, one of the most active peptides found so far, were modified by various residues. The discussion of conformationally relevant parameters proves that neither backbone conformations nor populations of aromatic side chain rotamers were altered by these substitutions. The potency of these derivatives in a cytoprotection assay varies by at most one order of magnitude (more or less active than the parent peptide 1a). A qualitative evaluation of lipophilic, steric, and charge effects reveals the dominance of lipophilic effects of aromatic residues; the most potent compounds contain aromatic substructures in the side chain of Lys4.

Animals↗
PubMed1988

Peptide conformation. 48. Conformation and biological activity of proline containing cyclic retro-analogues of somatostatin.

Six cyclic retro-analogues of the peptide hormone somatostatin have been synthesized using the solid phase technique. The peptides cyclo(-Xaa1-Phe2-Thr3-Lys4-Ybb5-Phe6-) and cyclo(-Phe1-Xaa2-Thr3-Lys4-Ybb5-Phe6-) with Xaa = D- or L-Pro and Ybb = D- or L-Trp were cyclized via the azide method. The conformations of the cyclic hexapeptides in DMSO-d6 solution were determined by a number of homo- and heteronuclear two-dimensional n.m.r.-techniques including 2D rotating frame NOE-spectroscopy. Two-step coherence transfers, ROE and chemical exchange, are observed for the first time in ROESY spectra. The backbone conformation of the all-trans cyclopeptides consists of a beta-turn containing the Pro residue in the position i + 1. These retro-analogues of somatostatin exhibit a high activity in the inhibition of cholate and phalloidin uptake by liver cells (cytoprotective effect); however, the hormonal activities of the natural hormone are completely suppressed. The constitutional and conformational requirements for the cytoprotective activity are discussed.

Amino Acid Sequence↗
PubMed1988

[The effect of subcutaneous nitrosamine injections on the origin of tumors of the liver and their inhibition by vitamin C].

Experiments were conducted on Wistar rats for the purpose of finding out, whether peroral vitamin C application is capable of inhibiting carcinogenesis through subcutaneous injection of nitrosamine. One group of animals received injections of N-nitrosodiethylamine, while high doses of vitamin C were additionally administered to a second group in drinking water. Vitamin C only was given to a third group (control). Numerous liver carcinomas developed in response to nitrosamine application. No numerical difference was found to exist between the groups with and without vitamin C.

Animals↗
PubMed1987

The presence of enkephalin-like substances in the eyestalk and brain of the land crab Gecarcinus lateralis.

The eyestalk of the land crab, Gecarcinus lateralis, is rich in Met-enkephalin-like materials. Leu-enkephalin, if present, is at a level which is below the sensitivity of our assay. The brain (cerebral ganglion) of this organism contains both Met- and Leu-enkephalin-like materials. Material which was reactive with our Met-enkephalin antibody was also detected in a peak that migrated after Leu-enkephalin. This biochemical study confirms earlier immunohistochemical reports which indicated that opioid substances are present in crustaceans. It also strongly supports the concept that opioid mechanisms are a product of early evolution and further demonstrates that the sequence of the smaller opioid compounds has been conserved.

Animals↗
PubMed1987

Molecular dynamics simulations of cyclosporin A: the crystal structure and dynamic modelling of a structure in apolar solution based on NMR data.

The conformation of the immunosuppressive drug cyclosporin A (CPA), both in apolar solution and in crystalline state, has been studied by computer simulation techniques. Three molecular dynamics (MD) simulations have been performed: one modelling the crystal structure and two modelling the structure in apolar solution, using a restrained MD approach in which data from nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy are taken into account. The simulation of the crystalline state (MDC) concerns a system of 4 unit cells containing 16 cyclosporin A molecules and 22 water molecules, which is simulated using crystalline periodic boundary conditions. The simulations modelling the apolar solvent conformation (MDS) concern one isolated cyclosporin A molecule. In these simulations an extra term in the interatomic potential function is used, which forces the molecule to satisfy a set of 57 atom-atom distance constraints originating from nuclear Overhauser effects (NOEs) obtained from NMR spectroscopy and one distance constraint deduced from IR spectroscopy. From a comparison of the results of the crystal simulation to those of the X-ray experiment in terms of structure, atomic fluctuations, hydrogen bond pattern, etc., it is concluded that the force field that is used yields an adequate representation of crystalline cyclosporin A. Secondly, it is shown that the dynamic modelling technique that is used to obtain a structure in a polar solution from NMR distance information works well. Starting from initial conformations which have a root mean square difference of 0.14 nm both distance restrained MD simulations converge to the same final solution structure. A comparison of the crystal structure of cyclosporin A and the one in apolar solution shows that there are significant differences. The overall difference in atomic positions is 0.09 nm for the C alpha atoms and 0.17 nm for all atoms. In apolar solution, the molecule is slightly more bent and the side chains of 1 MeBmt and 10 MeLeu adopt a different conformation.

Computer Simulation↗
PubMed1987

Comparative in vitro activity of A-56268 (TE-031) against gram-positive and gram-negative bacteria and Chlamydia trachomatis.

The in vitro activity of A-56268 (TE-031) was determined and compared with that of 13 antibiotics against 401 gram-positive and gram-negative bacteria and 11 strains of Chlamydia trachomatis. A-56268 was very active against methicillin-susceptible Staphylococcus aureus and Neisseria gonorrhoeae, and was among the most active of the agents tested against Listeria monocytogenes, streptococci and Chlamydia trachomatis. It was moderately active against Haemophilus spp., Vibrio spp., Campylobacter jejuni and Campylobacter fetus subsp. fetus. It was inactive against enterococci, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Campylobacter coli, Salmonella spp., Shigella spp. and Yersinia enterocolitica. A-56268 was not consistently bactericidal or more active than erythromycin for any organism except Chlamydia trachomatis.

Animals↗
PubMed1987

Synthesis of a cyclic retro analogue of somatostatin suitable for photoaffinity labelling.

Cyclic somatostatin analogues containing the modified retro sequence of the amino acids Phe7 to Phe11 of the natural compound have been found to exhibit high activity for cytoprotection of rat hepatocytes against cell poisons such as phallotoxins and galactosamine. Cyclo(-Phe(p-NH(1-14C)Ac)-Thr-Lys(CO(p-N3)C6H4)-Trp-Phe-D-Pro), a photoreactive and radioactive analogue of one of the most active cyclohexapeptides, was synthesized by a combination of solid phase technique and classical solution peptide synthesis. This peptide labels the same proteins in rat liver cell membrane that are modified by photolysable derivatives of bile acids, phalloidin and antamanide.

Affinity Labels↗
PubMed1987

Conformational analysis of a cyclic thymopoietin-analogue by 1H n.m.r. spectroscopy and restrained molecular dynamics simulations.

The internuclear distances of the cyclic thymopoietin derivative c[D-Val-Tyr-Arg-Lys-Glu] have been determined using two-dimensional nuclear Overhauser n.m.r. spectroscopy. These distances are used as constraints for a restrained Molecular Dynamics (MD) simulation. The two starting structures used for the calculations consist of a beta and gamma turn for model 1 and two gamma turns for model 2. The rms difference in atomic positions of the two conformations is 0.242 nm. They converge during the restrained MD simulation to the same final structure. The positional rms difference of the time averaged (5-14 ps) conformations is 0.011 nm. The hydrogen bond pattern is similar to that of model 1, but in addition we find three more gamma turns. The vicinal NH-C alpha H couplings agree well with those calculated from the time averaged structures.

Magnetic Resonance Spectroscopy↗
PubMed1987

Serum alanine aminotransferase levels and prevalence of hepatitis A, B, and delta in outpatients.

We investigated the relationship between alanine aminotransferase (ALT) levels and the prevalence of serologic markers of hepatitis A, hepatitis B, and delta hepatitis in an outpatient population. Sera submitted for routine biochemical testing from 4669 patients were grouped according to ALT level (normal and 1 to 2.5, 2.5 to 5.0, and more than five times the upper limit of normal). Serologic evidence of acute hepatitis A or acute or chronic hepatitis B was detected in 6.1% of specimens with elevated ALT levels compared with 1.3% with normal ALT levels. Patients with ALT levels greater than 2.5-fold and fivefold elevated were associated with a 9.3% and a 15.1% prevalence, respectively, of markers of acute or chronic hepatitis. Antibody to delta hepatitis was detected in nine subjects, all of whom also had serologic evidence of chronic hepatitis B. A retrospective chart review of 80 patients with serologic evidence of acute or chronic hepatitis revealed that 51% of cases were previously undiagnosed, most of which were in the low ALT groups. Hepatitis serologic testing may be indicated in outpatients with unexplained elevations of the ALT level.

Acute Disease↗
PubMed1987

[Early cancer of the exocrine pancreas: diagnosis and prognosis].

Early pancreatic carcinoma is defined as a tumor of less than 2 cm in diameter, limited to the pancreas without extension to adjacent structures or organs and without lymph-node and distant metastasis (T1a, N0, M0). In analysing 693 pancreatic cancer patients seen at the Surgical Clinic of Erlangen since 1969 we found only 3 early lesions (0.4%). There is a variety of diagnostic signs like unexplained abdominal pain, the development of pancreatic insufficiency, weight loss in excess of 10%, sudden onset of diabetes and elevation of serum and urine amylase. These early symptoms should be clarified by special pancreatic screening tests (ERCP, CT, US, angiography). CT and US alterations may be missing, because of the small tumor size. The proof of a pancreatic duct stenosis indicates laparotomy and resection. One of three of our patients survived longer than 6 years without recurrence. As reported, the 5-year-survival rate of early pancreatic cancer is 86%.

Biopsy, Needle↗
PubMed1986

[Pregnancy anamnesis and delivery in females with abnormalities of the internal genitalia].

The ability to deliver a living infant was examined in 65 women with genital malformations, in a retrospective clinical study. 87 deliveries resulted, the overall abortion rate was 35%. 44% of pregnancies proceeded without any complications, in 46% the first pregnancy led to the birth of a living child. Classification of genital malformations displayed a dominancy of severe forms like uterus duplex, bicornis and septus. Comparison of severe and mild uterovaginal anomalies revealed no significant differences concerning course and duration of pregnancy, birth weight and perinatal outcome of the newborn, whereas frequency of operative deliveries raised significantly in the group of severe defects, Apgar scores after one minute appeared significantly lower. A remarkable accumulation of breech presentations (50%) in combination with increased obstetric complications led to 82% of operative deliveries. The birth of 58% of boys caused a shifting of the sex ratio. The perinatal offspring was encouraging; 73% of the newborn could leave the clinic together with their mothers.

Abortion, Habitual↗
PubMed1986

Cytoprotective properties of somatostatins.

Secretion of many hormones is inhibited by regular cyclic somatostatin-14. Since additional cytoprotective properties of this hormone have been described, the question arises of whether analogs of somatostatin with increased endocrine activity may also exert increased cytoprotective activity. It could be shown that the endocrine and the cytoprotective property of somatostatin-14 must have different modes of action. In analogs of somatostatin with increased endocrine activity the cytoprotective effect is also increased. A maximal increase in the cytoprotective effect of certain analogs of somatostatin is accompanied by a loss of endocrine activity.

Amino Acid Sequence↗