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Biomedical subjects

K Bauer

Publications and source records attributed to K Bauer.

At least 199 records · Page 11Linked to original sources

Evidence for a protective influence of blood group A phenotype on X-ray signs of ankylosing spondylitis in HLA-B27 positives.

A total of 148 cases of HLA-B27 positive cases of suspected early ankylosing spondylitis were investigated for the influence of ABH-phenotypes. The 70 patients sharing X-ray signs of the disease had a significantly lower frequency of the A-phenotype, the 78 X-ray negatives showed an A excess. The positive protective effect of phenotype A on the development of the disease in HLA-B27 positives is discussed.

ABO Blood-Group System↗

Establishment and characterization of a neuroendocrine skin carcinoma cell line.

A neuroendocrine skin carcinoma cell line MKL-1 has been established from a nodal metastasis in a 26-year-old patient. The line grows as irregularly outlined, loosely packed floating aggregates lacking central necrosis. MKL-1 is hyperdiploid and has a mean doubling time of 120 hours. Xenografts of 2 X 10(7) MKL-1 cells produce tumors in nude mice at 4 to 6 weeks after subcutaneous inoculation. The xenografts were morphologically indistinguishable from the original skin primary and the nodal metastasis. Electron microscopy revealed sparse membrane-bound neurosecretory granules, and conspicuous, paranuclear aggregates of intermediate filaments. Immunohistochemical study showed diffuse and consistent staining with neuron-specific enolase, while bombesin, adrenocorticotrophic hormone, Leu-enkephalin, substance P, and vasoactive intestinal polypeptide displayed heterogeneous and variable expression. Uniform staining of all cells appearing as cytoplasmic fibrils and paranuclear aggregates was noted with antibodies to cytokeratin. Appreciable amounts of cytokeratin polypeptides 8, 18, and 19 and IT protein were seen on two-dimensional gel electrophoresis of cytoskeletal preparations from MKL-1 cells and from tumor-rich frozen sections. Immunostaining also showed coexpression of neurofilaments arranged in paranuclear aggregates; gel electrophoresis and immunoblotting demonstrated the presence in MKL-1 cells of prominent amounts of the small neurofilament polypeptide. Focal expression of desmoplakin was noted in the xenografts. The cells reacted with monoclonal antibodies anti-Leu-7 and anti-Leu-M1 but did not react with antibodies to human lymphocyte antigens (HLA)-A, HLA-B, and HLA-C. Cytogenetic analysis revealed the presence of 3 chromosomally abnormal cell lines with the majority of metaphase cells demonstrating a gain of an isochromosome of the short arm of chromosome 5. Thus, MKL-1 cell line shares several characteristics with small cell neuroendocrine bronchopulmonary carcinoma cell lines but shows distinct cytogenetic abnormalities.

Adult↗

Characterization of two carnosine-degrading enzymes from rat brain. Partial purification and characterization of a carnosinase and a beta-alanyl-arginine hydrolase.

From rat brain extracts, two carnosine-degrading enzymes have been identified and partially purified by ion-exchange chromatography, hydrophobic interaction chromatography on phenyl-Sepharose CL-4B and gel filtration. These enzymes exhibit distinct differences in their chemical characteristics and substrate specificities. One enzyme, designated carnosinase, preferentially hydrolyzes carnosine and exhibits a low Km value (0.02 mM) towards this substrate. Carnosinase also degrades anserine but not homocarnosine or homoanserine. The other carnosine-degrading enzyme hydrolyzes beta Ala-Arg considerably faster than carnosine and, therefore, has been tentatively designated beta Ala-Arg hydrolase. This enzyme exhibits high Km values with carnosine (Km = 25 mM) and beta Ala-Arg (Km = 2 mM). Homocarnosine and gamma-aminobutyryl-arginine are not degraded by beta Ala-Arg hydrolase. Neither enzyme is inhibited by agents reactive on activated hydroxyl groups, such as diisopropyl fluorophosphate, and also not by a variety of peptidase inhibitors of microbial origin or from other sources. Carnosinase is also not inhibited by bestatin but beta Ala-Arg hydrolase, although not an aminopeptidase, is strongly inhibited by this aminopeptidase inhibitor (IC50 = 50 nM). While carnosinase is strongly inhibited by thiol-reducing agents such as dithioerythritol and 2-mercaptoethanol, beta Ala-Arg hydrolase is stabilized and activated by these substances. Both enzymes are strongly inhibited by metal-chelating agents. Carnosinase, however, is not dependent on exogeneously added metal ions and is strongly inhibited by Mn2+ as well as by heavy metal ions. In contrast, beta Ala-Arg hydrolase requires Mn2+ ions for full enzymatic activity. Based on these differences, selective incubation conditions could be evaluated in order to determine specifically both enzyme activities in crude tissue extracts. In rat, both enzymes are present in all tissues tested, except skeletal muscles, but considerable differences in their relative distribution among different tissues are also observed.

Animals↗

Role of lysines in ion selectivity of bacterial outer membrane porins.

The epsilon-amino groups of available lysine residues of the OmpC, OmpF and PhoE porin proteins of Escherichia coli and of the protein P porin of Pseudomonas aeruginosa, were modified by the bulky reagent trinitrobenzenesulphonic acid. Approximately 78% of the lysines of the anion-selective protein P and PhoE porins were modified whereas only 40-50% of the lysines of the cation selective OmpF and OmpC porins were altered. After modification, the three E. coli porins had very similar high selectivities for cations over anions, in contrast to the native porins which varied 86-fold in ion selectivity. Despite the large size of the trinitrophenyl group attached to modified lysines (i.e., a disc of approx. 0.86 nm diameter X 0.36 nm high) relative to the reported size of the constrictions of the E. coli porins (1.0-1.2 nm diameter), only the anion-selective PhoE porin was substantially blocked after trinitrophenylation. The protein P porin channel was relatively unaffected by trinitrophenylation, in contrast to previous data showing dramatic effects of acetylation of lysines on protein P conductance and selectivity. This favoured a model in which the critical lysines involved in anion binding by protein P were present in a constriction of the channel that was too small for trinitrobenzenesulphonic acid to enter. Overall, the data suggest that both the number and relative position of charged lysines are major determinants of ion selectivity.

Anions↗

Specific inhibition of post proline cleaving enzyme by benzyloxycarbonyl-Gly-Pro-diazomethyl ketone.

N-Benzyloxycarbonyl-Gly-Pro-diazomethyl ketone (Z-Gly-Pro-CHN2) was synthesized and tested as inhibitor of the post proline cleaving enzyme from bovine brain. The compound was found to inactivate the enzyme completely and irreversibly at low concentrations (0.3 microM) without affecting other proteolytic enzymes such as post proline dipeptidyl aminopeptidase, pyroglutamate aminopeptidase or trypsin. Substrates of post proline cleaving enzymes such as luliberin (LH-RH; pyroGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) and Benzyloxycarbonyl-Gly-Pro-Ala protected the enzyme from the reaction with Z-Gly-Pro-CHN2. Thus, Z-Gly-Pro-CHN2 seems to be an active site directed, specific inhibitor of post proline cleaving enzyme. When administered intraperitoneally to rats, this inhibitor (8 mg/kg) completely inactivated the post proline cleaving enzyme in all tissues studied including brain. Therefore, Z-Gly-Pro-CHN2 should be a valuable tool for studies on the physiological function of this enzyme within the metabolism of neuropeptides.

Animals↗

Histiocytosis X. Flow cytometric DNA-content and immunohistochemical and ultrastructural analysis.

A 76-year-old man developed a generalized orange-red nodular eruption associated with constitutional symptoms. A biopsy specimen of a nodule revealed an extensive infiltration of histiocytes with relatively abundant cytoplasm and folded nuclei. Electron microscopy showed Langerhans' cell granules, which confirmed the diagnosis of histiocytosis X. Results of immunohistochemical studies revealed a pattern of antigen expression usually found in histiocytosis X, including Ia, T6, and S100. Analysis of the DNA content of the cells with flow cytometry revealed an aneuploid peak. The patient responded partially to topical mechlorethamine hydrochloride therapy.

Adult↗

A rapid method for the evaluation of nerve conduction blocking compounds.

A simple and easily accessible cockroach nerve preparation is described. Afferent potentials elicited by electric stimulation of the cercus showed remarkable stability, providing a fairly adequate background for pharmacological experimentation. Type I and type II pyrethroids were tested on the nerve preparation, and the results were compared with toxicity data obtained on the same species. Blockade of nerve conduction showed positive correlation (r = 0.804) with lethal effects. The preparation would be useful for determining neuronal point of attack of test compounds and the study of pyrethroids.

Animals↗

In vivo clearance of antibody-sensitized human drug carrier erythrocytes.

Antibody coating of resealed drug carrier erythrocytes may be useful for drug targeting to the reticuloendothelial system. We have investigated the survival in the circulation of anti-Rh antibody (IgG anti-D)-coated autologous erythrocytes loaded with gentamicin by hypoosmotic dialysis. Five subjects were injected with 15.2 +/- 0.4 ml and five additional subjects with 62.8 +/- 1.5 ml carrier cells. Survival of the cells was monitored by intraerythrocytic gentamicin concentration in blood. In the first subject group initial t1/2 was 0.21 +/- 0.06 hours and terminal t1/2 was 1.71 +/- 0.36 hours. In the second group initial t1/2 was 0.59 +/- 0.21 hours followed by a slow phase with a t1/2 of 89 +/- 28 hours. Results indicate that rapid drug delivery to the reticuloendothelial system by antibody-sensitized carrier erythrocytes is possible, but small volumes of erythrocytes seem more efficient.

Adult↗

Survival of gentamicin-loaded carrier erythrocytes in healthy human volunteers.

Resealed erythrocytes are potential slow release carriers for drugs and enzymes. We have investigated carrier erythrocyte survival in human volunteers using gentamicin (G) as encapsulated cell marker; G was readily incorporated into red cells by hypo-osmotic dialysis (87% efficiency of incorporation) and did not exit from carrier cells in vitro. Six healthy young volunteers were injected with 59 +/- 7 ml carrier erythrocytes containing 56 +/- 13 mg G. G levels were measured in plasma and haemolysed whole blood by RIA. After an initial phase of cell loss (up to 4.5 h post-injection) the carrier erythrocytes survived in circulation with a half-life of 22 days, as was indicated by intracellular G concentration. G levels were detectable in plasma during the first 90 min after injection. This indicates haemolysis of some carrier cells. In conclusion, carrier erythrocytes appear to circulate longer than any other drug carrier under investigation and may well serve as innocuous slow release system.

Adult↗

B-immunoblastic lymphoma arising in angioimmunoblastic lymphadenopathy.

We present a female patient with a B-immunoblastic lymphoma of the IgM-lambda type arising in angioimmunoblastic lymphadenopathy. An increased ratio of helper/inducer to suppressor/cytotoxic lymphocytes in the lymph node could have triggered the proliferation of B cells. Evolution of IgM cryoglobulinemia was paralleled by malignant transformation in the lymph node. A short-term in vitro chemosensitivity test could predict response to COP combination chemotherapy suggesting that in vitro chemosensitivity testing can be useful for the therapeutic management of angioimmunoblastic lymphadenopathy.

Antineoplastic Combined Chemotherapy Protocols↗

Viriplanin A, a new anthracycline antibiotic of the nogalamycin group. I. Isolation, characterization, degradation reactions and biological properties.

Viriplanin A, a new anthracycline antibiotic produced by Ampullariella regularis strain SE 47, was isolated from a raw product that demonstrated activity against Herpes simplex viruses. Based on spectroscopic data, the structure of the aglycone, viriplanol, was determined, and the antibiotic was found to contain the sugar moieties 2-deoxy-L-fucose, 4-O-mesaconoyl-L-diginose and decilonitrose. In solution viriplanin A is very unstable to light. The antibiotic belongs to the nogalamycin group and is related to arugomycin and decilorubicin.

Actinomycetales↗

A membrane bound substance P degrading endopeptidase from rat brain.

From rat brain, a membrane bound substance P-degrading endopeptidase (SPE) was purified 1580 fold to near homogeneity. After extraction with 10 mM CHAPS, the enzyme preparation was subjected to ion exchange chromatography on DEAE-cellulose, adsorption chromatography on hydroxyapatite, gelfiltration through Ultrogel AcA 44 and FPLC on Mono Q. This enzyme of 70,000 molecular weight is optimally active at pH 7.5. Metal chelators (EDTA and EGTA) and sulfhydryl modifying reagents (N-ethylmaleimide and p-chloromercuriphenylsulfonic acid) are strongly inhibitory while the serine-protease inhibitor diisopropyl-fluorophosphate does not effect the enzyme activity. The enzyme is strongly inhibited by bacitracin but not by phosphoramidon and captopril. Degradation of substance P is strongly inhibited by neurotensin, somatostatin, ACTH 1-39, and less effectively by LHRH but not by Leucine-enkephalin. Substance P is preferentially hydrolyzed at the Gln6-Phe7 peptide bond but fragmentation at the Pro4-Gln5, Gln5-Gln6,Phe7-Phe8 and Gly9-Leu10 bonds was also observed.

Animals↗

[Experiences with local administration of herd-specific vaccines].

The results of oral vaccination of 388 calves with herd-specific vaccines against E. coli are described. Innocuity was optimal, whereas the potency was estimated not as efficient as parenteral vaccination of the dam (in 22% of the cases), i.e., transient diseases in vaccinated calves occurred there. Further the results of intranasal vaccination of 496 cattle against salmonellosis are reported. Salmonella excretion in the faeces was stopped within 1-3 weeks post vaccination in 75% of the herds. In one case it took 3 months to reach this effect. A few permanent excretor cattle remained in two other cases.

Administration, Oral↗