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Biomedical subjects

E Ziegler

Publications and source records attributed to E Ziegler.

At least 19 recordsLinked to original sources
PubMed1995

Picornavirus 2A proteinase-mediated stimulation of internal initiation of translation is dependent on enzymatic activity and the cleavage products of cellular proteins.

Poliovirus and human rhinovirus 2A proteinases are known to stimulate translation initiation on the cognate viral Internal Ribosome Entry Segments (IRESes). The molecular mechanism of this translational transactivation was investigated in vitro using dicistronic mRNAs containing picornaviral IRESes as the intercistronic spacer and purified human rhinovirus type 2 and coxsackievirus B4 2A proteinases. The stimulation achieved on the HRV2 IRES in the presence of the cognate 2A proteinase at 1 microgram/ml was twofold; the maximum stimulation at 100 micrograms/ml was fivefold. The IRESes and proteinases from rhino- and enteroviruses were interchangeable; however, stimulation of translation initiation on a cardiovirus IRES by these proteinases was minimal. Studies using an inhibitor or a mutant 2A proteinase demonstrated that translation stimulation requires 2A-mediated enzymatic conversion of some cellular component(s). The HRV2 2A proteinase also stimulated translation initiation on full-length viral RNA, suggesting that 2A proteinase-mediated stimulation of IRES-driven translation has a physiological role.

Base Sequence↗
PubMed1995

Foot-and-mouth disease virus Lb proteinase can stimulate rhinovirus and enterovirus IRES-driven translation and cleave several proteins of cellular and viral origin.

Rhinovirus and enterovirus 2A proteinases stimulate translation initiation driven from the cognate internal ribosome entry segment (IRES) (S. J. Hambidge and P. Sarnow, Proc. Natl. Acad. Sci. USA 89:10272-10276, 1992; H.-D. Liebig, E. Ziegler, R. Yan, K. Hartmuth, H. Klump, H. Kowalski, D. Blaas, W. Sommergruber, L. Frasel, B. Lamphear, R. Rhoads, E. Kuechler, and T. Skern, Biochemistry 32:7581-7588, 1993). Given the functional similarities between the foot-and-mouth disease virus (FMDV) L proteinase and these 2A proteinases (autocatalytic excision from the nascent viral polyprotein and cleavage of eIF-4 gamma), we investigated whether the FMDV L proteinase would also be able to stimulate translation initiation. We found that purified recombinant FMDV Lb proteinase could stimulate in vitro translation driven from a rhinovirus or enterovirus IRES by 5- to 10-fold. In contrast, stimulation of translation initiation on a cardiovirus IRES by this proteinase was minimal, and stimulation of translation driven from the cognate FMDV IRES could not be evidenced. Studies using an inhibitor or a mutant Lb proteinase indicated that stimulation of IRES-driven translation is mediated via proteolysis of some cellular component(s). Our studies also demonstrated that the Lb proteinase is capable of stimulating initiation of translation on an uncapped cellular message. Unexpectedly, and in contrast to the 2A proteinases, the Lb proteinase specifically cleaved the products of the two reporter genes used in this study: Xenopus laevis cyclin B2 and influenza virus NS. Therefore, we also set out to investigate the requirements for substrate recognition by the Lb proteinase. Purified recombinant Lb proteinase recognized at least one mengovirus polypeptide and specifically cleaved human cyclin A and poliovirus replicase-related polypeptides. In the latter case, the site(s) of cleavage was located within the N-terminal part of polypeptide 3D. Sequence comparisons revealed no significant primary sequence similarities between the target proteins and the two sites already known to be recognized by the FMDV L proteinase.

Amino Acid Sequence↗
PubMed1992

Fibrin-enmeshed tobramycin liposomes: single application topical therapy of Pseudomonas keratitis.

Treatment of bacterial keratitis requires frequent application of topical antibiotics. We studied the efficacy of a single topical administration of tobramycin incorporated in large multivesicular liposomes and enmeshed in a fibrin sealant on rabbit corneas infected with Pseudomonas aeruginosa. One cornea each of 25 New Zealand albino rabbits was infected with P. aeruginosa. Twenty-four hours later, the animals were randomly divided into five groups of five. Group A received single hourly drops (50 microliters) of fortified tobramycin (14.5 mg/ml, total of 17.4 mg). Group B received a single topical application of 3.5 mg tobramycin, in 0.1 ml multivesicular liposomes, enmeshed in a fibrin sealant with an overlaying bandage contact lens. Group C was treated in the same manner as group B without the addition of fibrin sealant. Groups D and E served as nondrug-treated controls, with group D receiving topical fibrin-enmeshed liposomes devoid of tobramycin and group E receiving hourly topical balanced salt solution (BSS) drops. All animals were killed 24 h after initiation of therapy. Significantly fewer colonies of Pseudomonas were present in corneas of all three treated groups, as compared with the two nondrug-treated control groups (p less than 0.02). There were significantly fewer colonies of Pseudomonas in groups A and B as compared with group C (p less than 0.02). No significant difference was noted between a single administration of topical fibrinen-meshed tobramycin-encapsulated liposomes (group B) and 24 doses of hourly fortified topical tobramycin (group A, p greater than 0.05). Tobramycin-encapsulated megaliposomes may serve as a useful adjunct in treatment of Pseudomonas keratitis.

Administration, Topical↗
PubMed1991

Tobramycin liposomes. Single subconjunctival therapy of pseudomonal keratitis.

The authors compared 24 doses of hourly topical fortified tobramycin (Group A) therapy with a single subconjunctival administration of multivesicular megaliposome-encapsulated tobramycin (Group B) and free subconjunctival tobramycin (Group C) in treating a rabbit model of keratitis caused by Pseudomonas aeruginosa. One cornea each of 50 rabbits was infected with P. aeruginosa for 24 hr. The animals then were divided randomly into five groups of ten each. Groups A, B, and C were treated as described. Group D received liposomes without tobramycin and Group E, hourly balanced salt solution. Significantly fewer Pseudomonas colonies were present in the corneas of all three drug-treated groups (A, B, and C) compared with the two control groups (D and E) at 24 hr (P less than 0.005). Significantly fewer Pseudomonas colonies were present in Groups A and B compared with Group C (P less than 0.02). No significant difference was noted between Groups A and B (P = 0.30). Tobramycin encapsulated in megaliposomes may be useful in treatment of pseudomonal keratitis.

Administration, Topical↗
PubMed1990

Initial evaluation of a human immunoglobulin M monoclonal antibody (HA-1A) in humans.

A human monoclonal antibody (HA-1A) directed against bacterial endotoxin was administered to 15 patients with incurable malignant disease. No adverse effects were noted following single intravenous infusions of 0.05 to 100 mg. Pharmacokinetics were evaluated in nine patients receiving 10 mg (n = 3), 25 mg (n = 3), and 100 mg (n = 3). Seven of these patients had initial peak serum concentrations greater than 80% of predicted values with plasma disappearance curves fitting a one-compartment system and a plasma half-life of 31.5 h (range of 20.3-44.6 h). The peak serum concentrations and area under the curve values were proportional to the dose of HA-1A administered. One patient had a hypercatabolic state with low levels of serum albumin and IgM. He achieved 65% of the predicted value for peak serum concentration of HA-1A with a plasma half-life of 12.3 h. A second patient had detectable serum HA-1A for only 15 min following infusion without an adequate technical or biologic explanation. We were unable to demonstrate antibody to HA-1A in sera from these nine patients either prior to therapy or during 28 days postinfusion using a "double-antigen" radiometric assay. This study suggests that HA-1A human monoclonal antibody administration is well tolerated by patients. Phase I trials will need to be carried out to characterize further the pharmacokinetics and toxicity of HA-1A in patients with gram-negative sepsis.

Adult↗
PubMed1989

[Laser scan microscopy: a new imaging procedure in quality assessment of artificial lenses].

Laser-scan microscopy permits the evaluation of surfaces and deeper layers of an object by computer-assisted scanning with a laser beam. The reflected helium-neon or argon laser light is transmitted to a photodetector and after signal processing, to a frame store and a TV monitor. Imaging is realized by synchronous scanning and modulation of light intensity. Laser-scan microscopy revealed a smooth surface of both PMMA and HEMA lenses, whereas tears were detected in folded silicone implants. The physical and chemical homogeneity inside the three different materials was optimal. Compared to scanning electron microscopy, the quality of imaging is not as good with laser-scan microscopy. Nevertheless, one decisive advantage of the latter method is an analysis free of processing and artifacts, which permits a routine control of brand new and folded intraocular lenses.

Humans↗
PubMed1985

Organ procurement in Munich: financial and organizational aspects.

The Transplantation Center at the University of Munich is like all other German centers financially supported by the Insurance Companies via a non-profit organization (Kuratorium für Heimdialyse e.V.). The financial modalities are based on the arrangement that the Insurance Companies pay a certain amount for each transplantation to the non-profit organization. This institution, in cooperation with the University, uses this money to cover all extra expenses arising in the field of organ procurement as well as clinical transplantation (providing additional staff, equipment, etc). This model of a transplant center (ie, cooperation between University and non-University institutions) proved to be successful in the past 9 years. There was a steady increase of donor nephrectomies (200 donor kidneys in 1984) as well as kidney transplantations (171 transplantations in 1984).

Cadaver↗
PubMed1984

Immunoprophylaxis and immunotherapy of Gram-negative infections in the immunocompromised host.

Gram-negative infections remain a prominent cause of serious morbidity and mortality in hospitalized patients despite skilful antibiotic therapy and supportive care. A recently developed immunological approach to this problem is based on antiserum to an E. coli mutant (J5) which elicits antibody cross-reactive with a wide range of Gram-negative pathogens. The antitoxic and protective powers of E. coli J5 antiserum have been demonstrated in animal models. In carefully conducted clinical trials, J5 antiserum or J5 plasma of human origin has been established as a potent adjunctive therapy for the severe consequences of Gram-negative bacteraemia and in the prophylaxis of such infections in surgical patients. The question remains open whether such antiserum may have a similar prophylactic power in severely neutropenic patients. Clinical trials currently underway or soon to be started should help to clarify the practical prophylactic power of J5 hyperimmune globulin against shock and death in high-risk patients.

Animals↗
PubMed1980

[Treatment of hypertension with tenormin 100 (atenolol). A general practice study (author's transl)].

The effect and tolerance of a single daily tablet of Tenormin 100 in the treatment of essential hypertension was investigated in a private practice multicenter trial. 4083 Patients with mild to moderate essential hypertension (age range 15--89 years) were treated for four weeks. According to WHO criteria 83.4% of all patients were clearly hypertensive. At the end of the treatment 88.8% were under satisfactory control. The treatment was generally well tolerated. No hitherto unknown side effects occurred. The global therapeutic success rating, also taking into account the side effects, was confirmed mathematically and showed a success rate of 82% for Atenolol in this trial.

Adolescent↗
PubMed1979

[Correlations between the secular trend in sugar consumption in England and the secular increase of brain weight in adults in London between 1860 and 1940].

Significant positive correlations exist between the secular increase in brain weight of adults in London born between 1860 and 1940, and the secular trend in sugar consumption in the United Kingdom. These results of statistical analysis confirm once again the important bearing of excessive sugar consumption on the development of pre- and postnatal growth acceleration. The pathophysiological interactions of this development are discussed in the light of the experimentum naturae of the IDM (infant of the diabetic mother) and an attempt is made to explain the difference in brain weight increase between males and females.

Anthropometry↗
PubMed1979

[Changes in psychological performance parameters of concentration and critical flicker-fusion frequency with advancing age and in relation to diffuse cerebral arterial affections of the circulation].

Psychometric performance parameters and the critical flicker-fusion frequency are studied in various groups and in patients with chronic cerebral circulation trouble. Test d2 proves to be effective in the measuring of such impaired performance. There is a higher degree of correlation with Paul's addition test. A correlation between the performance parameters and the patient's age can be statistically substantiated. Among patients up to one third in the age group 55 and over show and affection of the cerebral performance turbances in spite of the absence of pathological clinical findings. The figure is twice as high in the group of patients undergoing treatment. The increased occurrence in old age shows the significance of pathological processes. There appears to be no relationship between critical flicker-fusion frequency and performance and stress factors. Individual correlations would support other physiological relations, such as an at present only hypothetical link with the psychic state (nervousness) of the test person. Our tables are suitable for practical purposes.

Adolescent↗
PubMed1978

[Development of standard psychological values for measuring brain performance at different ages under normal and pathological aspects (author's transl)].

The studies have shown that especially those tests that put the person tested under intense time pressure (d2 test and Pauli test) are suited for detecting diminished brain performance caused by cerebrovascular and other defects. The d2 test has proved to be the most sensitive and at the same time the most economical one (5 min). On the other hand the findings made by Löwe, Eitner et al. show that ageing people suffering from cerebrovascular disease but still able to work should be assigned work that requires a great deal of care rather than work that has to be done under time pressure. The determination of the flicker fusion frequency is seen in literature as a measure of vigilance. But the influences are of a very complex nature. We have found no correlation between the tests conducted by us, the attention test, the concentration pattern test and the Pauli test.

Adolescent↗