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Biomedical subjects

O Westphal

Publications and source records attributed to O Westphal.

At least 55 records · Page 3Linked to original sources
PubMed1984

Endotoxic properties of chemically synthesized lipid A part structures. Comparison of synthetic lipid A precursor and synthetic analogues with biosynthetic lipid A precursor and free lipid A.

Synthetic lipid A part structures corresponding structurally to a biosynthetic lipid A disaccharide precursor have been analyzed for endotoxic activity in several systems in vivo and in vitro. It was found that a synthetic beta-1,6-linked D-glucosamine disaccharide, which carries four molar equivalents of (R)-3-hydroxytetradecanoyl residues in positions 2, 3, 2' and 3' and phosphoryl groups in positions 1 and 4' (preparation 406), exhibited lethal toxicity, B lymphocyte mitogenicity, the capacity to engender prostaglandin formation in macrophages and to induce endotoxic tolerance, as well as serological lipid A antigenicity. On a weight basis, preparation 406 was of comparable activity to lipid A precursor and bacterial free lipid A. Preparation 406, like lipid A precursor, lacked, however, the ability to induce the local Shwartzman phenomenon and both preparations were of moderate pyrogenicity. Two further synthetic analogues which contained only one phosphoryl group (preparation 404 at C-4', preparation 405 at C-1) showed comparable or diminished activity depending on the test system employed, except in the capacity to inactivate complement where they exhibited, in contrast to preparation 406, significant activity. The results show that the endotoxic principle of lipopolysaccharides, as postulated previously is embedded in the lipid A component. Our results also suggest initial conclusions on the structural requirements for the expression of endotoxin activities.

Animals↗
PubMed1984

Haemorrhagic tumour necrosis following endotoxin administration. I. Communication: morphological investigation on endotoxin-induced necrosis of the methylcholanthrene (Meth A) tumour in the mouse.

Endotoxin induced necrosis of the Meth A mouse tumour has been investigated using macroscopic, histological and ultrastructural examination methods. On the 8th day after tumour cell transplantation, the animals received a relatively non-toxic dose of the Salmonella abortus equi endotoxin intravenously. The natural history of the tumour necrosis took the following course: The earliest morphological changes could be seen with the electron microscope 90 min after administration of the endotoxin, and were seen as an interstitial oedema with separation of the tumour cells. Haemorrhagic necrosis of the tumour was complete 4 hours after injection, and could be easily recognized with the naked eye. Rejection of the necrotic malignant tumour was complete two weeks after LPS administration. Only minor residual scarring of the belly-wall remained. Haemorrhagic tumour necrosis due to endotoxin can be compared with the localized Shwartzman reaction and probably involves tumour necrotizing factor (TNF). For complete destruction of a tumour by haemorrhagic necrosis the size of the tumour is critical. Certain regression after endotoxin administration depends upon additional T-cell-mediated immunity (provided the tumour is immunogenic). In contrast to the haemorrhagic necrosis, BCG-induced tumour regression is accompanied by granulomatous inflammation, which may be responsible for destruction of the tumour.

Animals↗
PubMed1984

Influence of the alkyllysophospholipid ET-18-OCH3 on methylnitrosourea-induced rat mammary carcinomas.

This study describes the efficacy of the alkyllysophospholipid 1-octadecyl-2-methoxy-Sn-racglycero-3-phosphocholine (ET-18-OCH3) in inhibiting the growth of methylnitrosourea-induced mammary carcinomas in Sprague-Dawley rats. In experiment A 2 X 10 mg/kg Et-18-OCH3 were administered daily for 10 weeks prior to manifestation of mammary carcinomas which resulted in a significant inhibition of median tumor number and median tumor volume per rat. Treatment of established tumors (experiment B) with 6 and 60 mg/kg ET-18-OCH3 daily for 3 weeks effected a stagnation in tumor growth for the higher dosage only with 90% tumor inhibition in comparison to untreated controls; at the same time, however, clear toxic effects were seen, thus indicating a narrow therapeutic index of ET-18-OCH3 in single-drug therapy. Combination of ET-18-OCH3 with compounds possessing a different toxicity spectrum is suggested.

Animals↗
PubMed1982

Treatment of undescended testes with intranasal application of synthetic LH-RH.

The effect of intranasal, synthetic LH-RH (Hoe 471) on undescended testes was investigated in: I. a double blind study comprising 50 patients given either placebo or 0.6 mg LH-RH daily and II. an open study comprising 50 patients with a daily dosage of 1.2 mg LH-RH. In both studies LH-RH was given for 4 weeks. Since some patients had bilateral undescended testes, 116 testes were treated in total. Patients' ages varied between 1 1/2 and 10 1/2 years, with a mean of 5 years. Clinical examination before, during and at end of treatment was performed by both the authors independently. In the placebo group, one testicular descent was seen, indicating difficulty in diagnosis. A therapeutic result, i.e. a significant move from the pretreatment location towards the bottom of the scrotum was seen in 60% of the testes, complete descent being seen in about 40%. In a follow-up study 6 months after treatment, in 23 cases with complete descent from a pretreatment inguinal position, relapse was seen in 5 patients (2 were located at scrotal neck, 3 at the pretreatment position i.e. inguinal). The best results were seen on testes located not too far from the scrotal neck, with the higher dosage of LH-RH and in patients less than 6 years of age. No significant hormonal changes (testosterone-, LH- or FSH-levels in peripheral blood) were seen during the study. Side effects were negligible.

Administration, Intranasal↗
PubMed1979

A lipopolysaccharide-binding cell-surface protein from Salmonella minnesota. Isolation, partial characterization and occurrence in different Enterobacteriaceae.

1. Protein extracts obtained from Salmonella minnesota Re mutant cells by treatment with EDTA/NaC1 solution contain a protein which exhibits high affinity to bacterial lipopolysaccharides. The isolation and partial characterization of this lipopolysaccharide-binding protein is described. 2. The protein was purified from EDTA extracts by a two-step procedure consisting of ion-exchange chromatography on CM-Sephadex and preparative polyacrylamide gel electrophoresis at pH 9.5. The yield of the total purification procedure was around 16%. 3. The resulting protein preparation was homogeneous on the basis of disc gel electrophoresis, dodecylsulfate gel electrophoresis, isoelectric focusing in polyacrylamide gel and immunoelectrophoresis. 4. The isoelectric point of the protein was found to be 10.3 at 4 degrees C. Its molecular weight determined by dodecylsulfate gel electrophoresis is 15000. Its amino acid composition is characterized by the absence of histidine and proline, a low content in tyrosine and high amounts of alanine, lysine, aspartic and glutamic acid residues, or their respective amides. 5. The lipopolysaccharide-protein association was shown to be mainly due to ionic interactions of the basic protein with negatively charged groups (probably phosphate and pyrophosphate groups) of the lipid A moiety. 6. Purified lipopolysaccharide-binding protein is immunogenic in rabbits, thus enabling the preparation of specific antiserum. 7. The protein is located at the surface of Salmonella minnesota Re mutant cells as revealed by antiserum absorption with total bacteria. Ferritin-labelling studies further demonstrated that it is evenly spread over the entire cell surface. 8. Comparative antiserum absorption studies using smooth and rough strains of Salmonella minnesota, Salmonella typhimurium, Escherichia coli, Klebsiella and Shigella revealed the presence of lipopolysaccharide-binding protein (or a serologically cross-reacting antigen) in most of the strains tested. From these results the protein can be considered as a common antigen of Enterobacteriaceae.

Amino Acids↗
PubMed1979

[Protective role of Salmonella R mutants in Salmonella infection in mice (author's transl)].

NMRI mice were immunized with acetone-killed bacteria of 6 salmonella R mutants, 5 homologous and 6 heterologous Salmonella S forms and 3 E. coli R mutants. The animals were then challenged with graded amounts of live S. typhimurium. The results show that the protection obtained was dependent on the number of immunizing injections and on the time interval between them. Thus in the case of Salmonella R-mutants two immunizations increased the LD50 of challenge by an index of two (log 10) compaired to one immunization. A third immunization led to only a small further increase, the protection however, was longer lasting. A 3 fold immunization with two Salmonella typhimurium mutants, one SR- and one Ra form, led to a protection comparable to that obtained with S form bacteria. In contrast to the R-mutants, with Salmonella typhimurium S form a high degree of long-lasting protection was achieved already after a single immunization, and was not increased significantly by repeated injections. In animals immunized with Salmonella typhimurium S form the difference between non-lethal and 100% lethal challenge dose varied by a factor of 10 (one injection dose). In contrast, in animals immunized with Salmonella R mutants the above differences were more gradual extending over 3, 4 or more infection doses. This was also true for animals immunized with lower doses of S. typhimurium S form and for the non-immunized control animals. For comparison the protective effect of heterologous Salmonella S forms and of E. coli R-mutants was studied. These were found to be less effective in affording protection to Salmonella typhimurium than the above Salmonella R forms. The various strains used for immunization may be placed in the following sequence in order of decreasing protection: Salmonella typhimurium S form, Salmonella R-mutants, heterologous Salmonella S forms, E. coli R mutants. In a parallel investigation the antibody inducing properties of Salmonella R mutants and heterologous Salmonella S forms were studied. In all cases homologous hemaglutinating antibodies to all the strains used for immunization were detectable. In immunization with Salmonella R mutants in addition to homologous titres, agglutinating antibodies to Salmonella typhimurium S form were also produced in significant amounts. There was, however, no correlation between the time of appearance of protection and that of appearance of antibodies nor between the hight of antibody titres and degree of protection. The detection of agglutinins to the infecting microorganisms represents therefore no valid criterium for the effectiveness of R mutants and heterologous Salmonella S forms as protective vaccines. From the present results it is concluded that in addition to the O antigen one or more further cell components exist which are involved in rendering animals immune to Salmonella typhimurium and probably also to other Salmonella S form bacteria.

Agglutination Tests↗
PubMed1979

Preparation and properties of a standardized lipopolysaccharide from salmonella abortus equi (Novo-Pyrexal).

The paper describes the preparation of the lipopolysaccharide from Salmonella abortus equi as obtained by standardized methods. The include the extraction with pehnol/water followed by phenol/chloroform/petroleum ether extraction, ultra-centrifugation, electrodialysis and conversion to the uniform sodium salt form. Chemical composition and physico chemical properties are described. The preparation, which is free from contaminants, was tested for local Shwartzman reactivity, pyrogenicity, lethal toxicity, mitogenicity, reactivity towards complement and tumoricidal action.

Animals↗