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Biomedical subjects

M Metzger

Publications and source records attributed to M Metzger.

At least 55 records · Page 3Linked to original sources
PubMed1991

Amplification of three threonine biosynthesis genes in Corynebacterium glutamicum and its influence on carbon flux in different strains.

The hom-thrB operon (homoserine dehydrogenase/homoserine kinase) and the thrC gene (threonine synthase) of Corynebacterium glutamicum ATCC 13,032 and the homFBR (homoserine dehydrogenase resistant to feedback inhibition by threonine) alone as well as homFBR-thrB operon of C. glutamicum DM 368-3 were cloned separately and in combination in the Escherichia coli/C. glutamicum shuttle vector pEK0 and introduced into different corynebacterial strains. All recombinant strains showed 8- to 20-fold higher specific activities of homoserine dehydrogenase, homoserine kinase, and/or threonine synthase compared to the respective host. In wild-type C. glutamicum, amplification of the threonine genes did not result in secretion of threonine. In the lysine producer C. glutamicum DG 52-5 and in the lysine-plus-threonine producer C. glutamicum DM 368-3 overexpression of hom-thrB resulted in a notable shift of carbon flux from lysine to threonine whereas cloning of homFBR-thrB as well as of homFBR in C. glutamicum DM 368-3 led to a complete shift towards threonine or towards threonine and its precursor homoserine, respectively. Overexpression of thrC alone or in combination with that of homFBR and thrB had no effect on threonine or lysine formation in all recombinant strains tested.

Carbon↗
PubMed1989

Pharmacokinetic and distribution analysis of variant forms of tissue-type plasminogen activator with prolonged clearance in rat.

Human tissue-type plasminogen activator (t-PA) is a glycoprotein used currently in thrombolytic therapy. Because of its rapid half-life (T1/2) of approximately five minutes, intravenous (IV) infusion of large doses (approximately 100 mg) are required in patients treated for myocardial infarction. To identify the determinant(s) on t-PA responsible for such rapid clearance, metabolically labeled forms of recombinant t-PA were analyzed in rats following IV administration. The following seven forms of t-PA were tested: (a) natural or glycosylated wild-type t-PA; (b) nonglycosylated wild-type t-PA; (c) delta F t-PA, which lacks the fibronectin fingerlike domain; (d) delta E t-PA, which lacks the epidermal growth factor (EGF) domain; (e) delta FE t-PA, which lacks both the finger and EGF domains; (f) delta FE3X t-PA, a form of delta FE t-PA in which Asn-linked glycosylation is prevented at all known glycosylation sites (Asn-117, 184, and 448; replaced by Gln); and (f) delta FE1X t-PA, a form of delta FE t-PA in which high-mannose-type glycosylation is prevented at Asn-117. Both glycosylated and nonglycosylated wild-type t-PA cleared in an exponential biphasic manner, with an initial alpha-phase T1/2 of 0.8 and 1.9 minutes, respectively. This result demonstrates that carbohydrate is not the primary mediator of the rapid clearance of t-PA. The liver was the primary organ responsible for uptake of these molecules. All other proteins tested, except for delta E t-PA, demonstrated primarily monophasic clearance patterns with T1/2 ranging between 12 and 27 minutes, and reduced uptake in the liver. delta E t-PA however, cleared in a biphasic manner with an alpha-phase T1/2 of 2.1 minutes. Results presented suggest that the clearance of t-PA is mediated by two distinct mechanisms. The primary determinant(s) responsible for modulating the rapid clearance of t-PA appears to be resident within the polypeptide sequence encoding the finger and/or EGF domains, with emphasis on the finger domain. A second and less significant contribution to clearance is defined by the presence and type of glycosylation.

Animals↗
PubMed1988

Human IL-3 and GM-CSF act synergistically in stimulating hematopoiesis in primates.

Interleukin-3 (IL-3) is a member of a family of growth factors, each of which supports the proliferation and development of hematopoietic precursors in culture. Although the biologic effects of the different hematopoietic growth factors have been well documented in different culture systems, it has only recently become possible to study the activities of these molecules in vivo. In comparison with the later acting hematopoietic growth factors granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor, IL-3 elicited a delayed and relatively modest leukocytosis when continuously infused intravenously in primates. The IL-3 infusion, however, greatly potentiated the responsiveness of the animal to subsequent administration of a low dose of GM-CSF. These results suggest that IL-3 expands an early cell population in vivo that subsequently requires the action of a later acting factor such as GM-CSF to complete its development. Optimal stimulation of hematopoiesis may be achieved with combinations of hematopoietic growth factors.

Animals↗
PubMed1988

A new chromosomal instability disorder confirmed by complementation studies.

Two sisters with a complex clinical pattern, including microcephaly, microgenia, defects of skin pigmentation, anal stenosis/atresia, and combined immunodeficiency together with spontaneous chromosomal instability and cellular hypersensitivity to X-rays and bleomycin are described. Complementation studies on heterokaryons proved that the underlying genetic defect is non-allelic with that of patients with ataxia telangiectasia (complementation groups AB-E) and the Nijmegen breakage syndrome, but identical with the case described by Conley et al. (1986).

Ataxia Telangiectasia↗
PubMed1987

Establishing a data base: the first step in effective management for day-treatment programs for children and adolescents.

A simple step-by-step plan for organizing and developing a computerized data base in a psychoeducational day-treatment program for children and adolescents is described. The plan is purposefully limited and simple in conception so that it can be replicated in freestanding and/or smaller programs, those who might not have the resources available when affiliated with a hospital or university. The article stresses the need for programs to make the commitment to begin a system of data collection. A table indicating measures and collection times is included.

Adolescent↗
PubMed1987

[Subperiosteal metastasis of esophageal adenocarcinoma].

The authors report an observation of a tibial subperiosteal metastasis of an esophageal cancer. Subperiosteal metastases are rare, appearing on plain radiography as a cortical lysis of a long bone with a "saucer" aspect. They were considered specific of a bronchogenic carcinoma. To the best of our knowledge this is the second observation of subperiosteal metastasis, whose primary tumor is not a broncho-pulmonary cancer.

Adenocarcinoma↗
PubMed1986

[Effect of adjuvant immunoglobulin therapy on infections in patients in an surgical intensive care unit. Results of a randomized controlled study].

A randomized controlled clinical trial was conducted on the effects of immunoglobulin in therapy for infections in 104 intensive care patients. At the first sign of infection, one group of 50 patients received an i.v. preparation of immunoglobulin (4 X 100 ml) combined with antibiotics. The other 54 control patients received antibiotics alone. The most common infections in these patients were pneumonia, septicemia, peritonitis and wound sepsis. Infections were significantly seldom the cause of death, especially in patients with high-risk surgery who had been treated with immunoglobulin (p less than or equal to 0.05). Likewise ventilation time in the high-risk surgery group averaged only 5.5 days for those receiving immunoglobulin as opposed to 12.7 days in controls (p less than or equal to 0.01). Whereas the control group, in particular patients with pneumonia, remained in intensive care an average of 21.5 days, those receiving immunoglobulin stayed only 14.8 days (p less than or equal to 0.01). In general, patients treated with immunoglobulin recovered more rapidly from infections than did controls (p less than or equal to 0.01).

Adult↗
PubMed1984

Pharmacological properties of the new orally active angiotensin converting enzyme inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl] -(1S,3S,5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498).

2-[N-[(S)-1-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S) - 2-azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498) can be characterized as a novel orally active non-sulfhydryl containing angiotensin converting enzyme inhibitor. Designed as a prodrug to improve the bioavailability Hoe 498 has to be deesterified to its active moiety Hoe 498-diacid to develop full inhibitory potency. The present study compares the basic pharmacological properties of Hoe 498 in rats and dogs to those of enalapril. In vitro assays revealed equal potency of both Hoe 498-diacid and enalaprilat. In vivo the inhibitory potency was judged by the ability to attenuate the pressor response induced by angiotensin I. The results indicate that Hoe 498 was approximately 10 times more potent than enalapril after oral intake in conscious rats or after intraduodenal administration in anaesthetized rats, whereas after intravenous injection both compounds exhibited equal potency. Hoe 498 was at least twice as potent as enalapril after oral or intraduodenal administration in dogs but about 4 times more potent than enalapril after intravenous injection. In conclusion, the obtained data point to a prodrug pathway for Hoe 498 which should be advantageous with regard to bioavailability, onset and duration of action and therefore promises to be favourable in the treatment of different cardiovascular diseases.

Angiotensin I↗
PubMed1984

Administration of antithymocyte serum to syphilitic rabbits inhibits development of resistance to reinfection with Treponema pallidum.

Three groups of female rabbits were inoculated i.v. with T. pallidum. One group of the animals was treated with horse anti-rabbit thymocyte serum (ATS) one day before and during the next two weeks after infection. Two other groups, one treated with normal horse serum (NHS) in the same way as the previous one and the other untreated, served as controls. After various time intervals, all the animals were tested for the content of T and B lymphocytes in the peripheral blood, humoral (VDRL and TPI tests), and cell-mediated (SDH test) responses. Two days after testing, animals of each group were challenged i.d. with T. pallidum, and observed for appearance of syphilitic lesions. The treatment of syphilitic rabbits with ATS caused a significant reduction in the number of T lymphocytes and a distinct inhibition of development of cell-mediated immunity associated with the lack of resistance to reinfection with T. pallidum till the 16th week of the infection; the level of B lymphocytes and the development of serological responsiveness was not affected by ATS treatment. The results are interpreted as indicating the protective role of cell-mediated immunity in syphilis.

Animals↗
PubMed1984

Enriched immune T cell suspension protects rabbits against infection with Treponema pallidum.

Four groups of rabbits were given intravenously (i.v.) enriched T or B lymphocytes derived from normal or immunized donor rabbits; 24 hrs later, all these animals were infected intradermally (i.d.) with T. pallidum in order to check their immune status. Only rabbits which received immune T cells showed a state of resistance to infection with T. pallidum, whereas recipients of lymphocytes of three other groups did not.

Animals↗
PubMed1982

In vitro combination effects of cefsulodin, moxalactam and cefoperazone with four aminoglycosides on nonfermenting nosocomial gram-negative bacteria.

The activity of moxalactam, cefsulodin and cefoperazone on 67 non-fermenting gram-negative bacterial strains isolated from patients with nosocomial infections was tested either alone or in combination with gentamicin, tobramycin, amikacin and netilmicin, respectively, by use of the checkerboard agar dilution technique. Cefsulodin was most active against Pseudomonas aeruginosa, cefoperazone was the most active cephalosporin tested against Pseudomonas fluorescens-putida and Acinetobacter antitratus. Cefoperazone-aminoglycoside interactions were found to be synergistic in only 2--5% of all strains, cefsulodin and moxalactam in combination with aminoglycosides were most potent against P. aeruginosa. Cefsulodin-gentamicin interactions were superior to other cephalosporin-amino-glycoside combinations.

Aminoglycosides↗
PubMed1981

Kunitz-type proteinase inhibitors derived by limited proteolysis of the inter-alpha-trypsin inhibitor. VI. Detection of a complex between immunoglobulin g and the inhibitory active part of the inter-alpha-trypsin inhibitor.

A latent trypsin inhibitor is released from denatured human serum proteins by proteolytic digestion with thermolysin. The latent inhibitor was enriched by chromatography on DEAE-Sephacel, Sephadex G-200, and Protein A-Sepharose, respectively. Immunological cross-section identified the latent inhibitor as a complex between IgG and the inhibitory active part of the inter-alpha-trypsin inhibitor.

Alpha-Globulins↗
PubMed1981

Treponemicidal activity of supernatants from cultures of sensitized lymphocytes.

It was found that lymphocytes secured from lymphoid organs or syphilitic rabbits, when cultured with ultrasonicate of T. pallidum (Tp-S) or phytohemagglutinin-P (PHA-P), released to the supernatant fluid a substance (ATL-anti-treponemal lymphotoxin) which exerted a direct killing effect on T. pallidum. Splenic lymphocytes were found much more active than lymphocytes isolated from popliteal and mesenteric lymph nodes, and the peripheral blood. The effect of some factors on release of the ATL by sensitized lymphocytes was established.

Animals↗
PubMed1980

Development of immunological responsiveness and resistance to infection with Treponema pallidum in rabbits given immune lymphocyte preparations.

Three groups of normal rabbits were administered: 1. viable lymphocytic cells; 2. lysates of lymphocytes obtained by freezing and thawing, and 3. low molecular weight dialyzable transfer factor (TF). The lymphocytes were derived from peripheral blood, lymph nodes, and spleens of rabbits: 1. cured of longlasting syphilitic infection by penicillin treatment, and 2. immunized with nonviable T. pallidum, exhibiting a good reactivity by tests for humoral and cell-mediated responses. All the three lymphocyte preparations were found to be able to transfer cell-mediated response as measured by the Macrophage Migration Inhibition Test (MMI) and the Skin Test for Delayed Hypersenitivity to Treponemal Antigens (SDH), from a reactive donor to the nonreactive recipient rabbit; the intensity of the response found in the recipient was roughly the same as in the donor. None of the lymphocyte preparations transferred humoral response, as measured by the TPI and VDRL tests. Only whole lymphocytic cells were found to be able to confer a stat of resistance to infection with T. pallidum on normal recipients.

Animals↗