Biomedical subjects

Joachim Schmid

Publications and source records attributed to Joachim Schmid.

5 recordsLinked to original sources

PubMed2006

A broad diversity of volatile carboxylic acids, released by a bacterial aminoacylase from axilla secretions, as candidate molecules for the determination of human-body odor type.

Human body odor is to a large part determined by secretions of glands in the axillary regions. Two key odoriferous principles, 3-methylhex-2-enoic acid (3MH2; 4/5) and 3-hydroxy-3-methylhexanoic acid (HMHA; 6) have been shown to be released from glutamine conjugates secreted in the axilla by a specific N(alpha)-acyl-glutamine aminoacylase (N-AGA) obtained from axilla isolates of Corynebacteria sp. However, the low number of different odorants reported in humans stands in contrast to the observed high inter-individual variability in body odors. Axilla secretions of individual donors were, therefore, analyzed in detail. The secretions were treated with N-AGA, analyzed by GC/MS, and compared to undigested controls. Over 28 different carboxylic acids were released by this enzyme from odorless axilla secretions (Table 1). Many of these body odorants have not been reported before from a natural source, and they include several aliphatic 3-hydroxy acids with 4-Me branches, 3,4-unsaturated, 4-Et-branched aliphatic acids, and a variety of degradation products of amino acids. The odor threshold of some of the acids was found to be in the range of 1 ng. Most of these compounds were present in all donors tested, but in highly variable relative amounts, and they are, thus, candidate molecules as key components of a 'compound odor' determining the individual types of human body odor.

Actinomycetales↗

PubMed2005

Model-based inference of gene expression dynamics from sequence information.

A dynamic model of prokaryotic gene expression is developed that makes considerable use of gene sequence information. The main contribution arises from the fact that the combined gene expression model allows us to access the impact of altering a nucleotide sequence on the dynamics of gene expression rates mechanistically. The high level of detail of the mathematical model is considered as an important step towards bringing together the tremendous amount of biological in-depth knowledge that has been accumulated at the molecular level, using a systems level analysis (in the sense of a bottom-up, inductive approach). This enables to the model to provide highly detailed insights into the various steps of the protein expression process and it allows us to access possible targets for model-based design. Taken as a whole, the mathematical gene expression model presented in this study provides a comprehensive framework for a thorough analysis of sequence-related effects on the stages of mRNA synthesis, mRNA degradation and ribosomal translation, as well as their nonlinear interconnectedness. Therefore, it may be useful in the rational design of recombinant bacterial protein synthesis systems, the modulation of enzyme activities in pathway design, in vitro protein biosynthesis, and RNA-based vaccination.

Base Sequence↗

PubMed2004

Identification of odoriferous sulfanylalkanols in human axilla secretions and their formation through cleavage of cysteine precursors by a C-S lyase isolated from axilla bacteria.

Human axillary odor is known to be formed upon the action of Corynebacteria sp. on per se odorless axilla secretions. Besides the known odoriferous acids, we report the occurrence in human axilla secretions of four odoriferous sulfanylalkanols, namely 3-sulfanylhexan-1-ol (3), 2-methyl-3-sulfanylbutan-1-ol (4), 3-sulfanylpentan-1-ol (5), and 3-methyl-3-sulfanylhexan-1-ol (6). These compounds have a pungent sweat/kitchen odor, also reminiscent of onions with some fruity connotations, and perception thresholds in the pg/l range. It was postulated that the odorless precursors for these compounds are cysteine conjugates. Bacterial isolates obtained from the human axilla and belonging to the Corynebacteria were, indeed, found to have the enzymatic capacity to release various thiols from cysteine conjugates. The metC gene, which is known to code for a cystathione-beta-lyase, was cloned from the axilla isolate Corynebacterium striatum Ax20 and heterologously expressed in E. coli. The pure recombinant enzyme cleaves various cysteine conjugates and has a similar substrate specificity as the cell homogenates of the wild-type. The recombinant enzyme was finally incubated with odorless axilla secretions and shown to release odoriferous thiols.

Axilla↗

PubMed2002

A specific bacterial aminoacylase cleaves odorant precursors secreted in the human axilla.

Human axillary odor is known to be formed upon the action of Corynebacteria sp. on odorless axilla secretions. The known axilla odor determinant 3-methyl-2-hexenoic acid was identified in hydrolyzed axilla secretions along with a chemically related compound, 3-hydroxy-3-methylhexanoic acid. The natural precursors of both these acids were purified from non-hydrolyzed axilla secretions. From liquid chromatography/mass spectrometry analysis, it appeared that the acids are covalently linked to a glutamine residue in fresh axilla secretions, and the corresponding conjugates were synthesized for confirmation. Bacterial isolates obtained from the human axilla and belonging to the Corynebacteria were found to release the acids from these odorless precursors in vitro. A Zn(2+)-dependent aminoacylase mediating this cleavage was purified from Corynebacterium striatum Ax20, and the corresponding gene agaA was cloned and heterologously expressed in Escherichia coli. The enzyme is highly specific for the glutamine residue but has a low specificity for the acyl part of the substrate. agaA is closely related to many genes coding for enzymes involved in the cleavage of N-terminal acyl and aryl substituents from amino acids. This is the first report of the structure elucidation of precursors for human body odorants and the isolation of the bacterial enzyme involved in their cleavage.

Amidohydrolases↗

PubMed2002

Machine scoring of Her2/neu immunohistochemical stains.

OBJECTIVE: To establish the feasibility of a machine scoring method for her2/neu immunohistochemistry in samples of breast carcinoma. STUDY DESIGN: A total of 65 consecutive cases of breast carcinoma with immunohistochemical stainingfor her2/neu by the Herceptest (Dako Corp., Carpinteria, California, U.S.A.) method (DAB chromogen with hematoxylin counterstain) were analyzed using an Extended Slide Wizard (Tripath Imaging, Inc., Burlington, North Carolina, U.S.A.) workstation running prototype software. Representative fields of view from the positive control, negative control and up to 10 fields from the stained tumor sample were captured interactively with a phased alternating line 3 CCD color camera. To determine the amount of specific membrane staining, chromogen separation of nuclear counterstain and membrane-positive stain was performed based on their respective absorption coefficients in the three color channels. The amount of specific membrane staining was scored based on a training set covering the rangefrom 0 to 3 + staining scores according to Dako. Manual scores of 2 + were tested for amplification by fluorescence in situ hybridization. RESULTS: The automated scoring results correlated highly with the manual scores obtained per the Herceptest (Dako) instructions (R2>.92). The results were obtained in real time in the interactive mode. CONCLUSION: Machine scoring of immunohistochemical stains is practical, rapid and inherently reproducible, especially for samples with 1+ and 2+ manual scores.

Breast Neoplasms↗