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Biomedical subjects

L Seidel

Publications and source records attributed to L Seidel.

34 records · Page 2Linked to original sources

Selection and characterization of new microorganisms for the manufacture of 9-OH-AD from sterols.

Using a special selection procedure, several mutants of Mycobacterium vaccae were isolated which were capable of converting sterols to 9 alpha-hydroxyandrost-4-ene-3,17-dion (9-OH-AD). Two mutants, Mycobacterium vaccae ZIMET 11052 and 11053, respectively, were further investigated. Strains of the species Mycobacterium fortuitum are mainly used for commercially obtaining 9-OH-AD from sterols. In contrast to the species Mycobacterium fortuitum the species Mycobacterium vaccae has not been reported to contain pathogenic strains. This seems an advantage for industrial application. Mutants with the ability of converting sterols to 9 alpha-hydroxysteroids have a defect in the steroid-1-dehydrogenase activity which is, however, only a partial one. The remaining activity may cause an undesirable degradation of the steroid nucleus. The steroid-1-dehydrogenase activity was tested using an assay developed by ATRAT (1986). We confirmed two apparently distinct steroid-1-dehydrogenases in Mycobacterium fortuitum NRRL B-8119 as reported by WOVCHA et al. (1979). One of them has an activity on androst-4-ene-3,17-dion (AD). The activity is increased by induction with sitosterol. The other one is active on 9-OH-AD. But Mycobacterium vaccae does not possess steroid-1-dehydrogenase activity on 9-OH-AD, and the AD specific steroid-1-dehydrogenase is not effected by sitosterol. The consequence is a high level of protection against steroid nucleus degradation yielding an effective accumulation of 9-OH-AD in fermentations with Mycobacterium vaccae mutants.

Androstenedione↗

Preclinical and clinical testing of radiolabelled monoclonal antibodies for immunoscintigraphy.

Immunoscintigraphy is a new method for in vivo diagnosis of diseases using monoclonal antibodies. Emphasis is placed on diagnosis of malignant tumors although the range of application includes a number of non-malignant diseases. To date, no European country has issued clear guidelines on the testing and registration of those monoclonal antibodies labelled with a radionuclide and used for diagnostic. This involves the risk of overregulation which would considerably reduce the applicability of the method. This holds particularly true since the complications initially anticipated with the use of such compounds did not occur. The conduct of immunoscintigraphy has evolved during the last few years. For reasons of applicability, but also and mainly for reasons of radiation hygiene, I-131 and finally also In-111 were abandoned as labelling nuclides and replaced by Tc-99m. The protein amount involved was reduced. Some false estimations, which were due to particularities or artifacts of the iodinated antibodies used at the beginning, had to be corrected: the representation of the liver in a scintigram is part of the physiological distribution of antibodies; and fragments of antibodies normally do not present the anticipated kinetic advantages. The clinical results obtained with colon carcinomas show that not only recurrencies and metastases, but also primary tumors can be detected with equally high sensitivity. In contrast, radioimmunotherapy does not yet seem as successful, at least against solid tumors.

Animals↗

[Immunoscintigraphy of colorectal cancers and specific immunotherapy of pancreatic cancers using monoclonal antibodies].

The routine application of immunoscintigraphy for the detection of colorectal carcinomas is now possible thanks to the development of the BW 431/31-F(ab')2-DTPA-In-111 or the BW 431/26-Tc-99m kits. The quick tumor localization (6 hours p.i.), the specificity and sensitivity (approximately equal to 90%) as well as the lack of side reactions argue for the quality of the reagents. The change from I-131 labelled murine monoclonal antibodies (MAbs) to In-111 or Tc-99m immunoconjugates in kit form resulted in a reduction of radiation dose for the patient down to 20% (In-111) or to 5% (Tc-99m) of the dose applied using I-131 labelled MAbs. The BW 250/183-Tc-99m conjugate suited for the immunoscintigraphic detection of inflammatory processes by in vivo labelling of granulocytes possesses the same favourable characteristics. The specific tumor immunotherapy of pancreatic carcinoma using MAb BW 494 points to interesting effects which have to be statistically confirmed in future clinical trials.

Antibodies, Monoclonal↗

Coexistence of nonsecreting and nonproducing light chain multiple myeloma.

A 61-year-old female patient presented with osteolytic skeletal lesions. Open rib biopsy disclosed tumor tissue which consisted of two types of cells: massive infiltrates of poorly differentiated lymphoplasmacytic cells were surrounded by large deposits of differentiated plasma cells. Serum immunoglobulins were normal. No light chains could be found in the urine. An immunoperoxidase technique was employed to detect intracellular immunoglobulins. While the partially differentiated cells were negative, the plasma cells were stained strongly positive for kappa light chains.

Female↗

[Isolation of streptothricin resistant mutants from E coli K12, strain A19].

Mutants with various levels of resistance to streptothricin were isolated from Escherichia coli K12, strain A19 after mutagenesis with N-methyl-N-nitro-N-nitroso-guanidine and ethylmethane-sulfonate. Nourseothricin, a mixture of streptothricin F and D was the selection agent. Spontaneous resistant mutants could not be found. The streptothricin-resistant mutant E. coli A19 Stcr 2/2/1 shows cross-resistance to some of the aminoglycoside antibiotics investigated, but no cross-resistance to chloramphenicol and chlortetracyclin. These results indicate similar mechanisms of action of streptothricin and aminoglycoside antibiotics.

Anti-Bacterial Agents↗

Gorham's disease of the clavicle with bilateral pleural effusions.

A patient with Gorham's disease (massive osteolysis, disappearing bone disease) of the right clavicle had bilateral sanguinous pleural effusions. Complete cure was achieved by removal of the bony remnants with the hemangiomatous mass which caused bone destruction, and by obliteration of the pleural spaces using repeated talcum insertion. In six out of seven previously described cases of Gorham's disease with pleural effusions, the patients died, while the only survivor had a unilateral chylous effusion.

Adult↗