Biomedical subjects

Stefan Schulz

Publications and source records attributed to Stefan Schulz.

At least 19 recordsLinked to original sources

PubMed2006

Analysing traces of autoinducer-2 requires standardization of the Vibrio harveyi bioassay.

Autoinducer-2 (furanosyl borate diester) is a biologically active compound whose role as a universal bacterial signalling molecule is currently under intense investigation. Because of its instability and the low concentrations of it found in biological samples, its detection relies at present on a bioassay that measures the difference in the timing of the luminescence of the Vibrio harveyi BB170 sensor strain with and without externally added AI-2. Here we systematically investigated which parameters affected the fold induction values of luminescence obtained in the bioassay and developed a modified protocol. Our experiments showed that growth and luminescence of V. harveyi BB170 are strongly influenced by trace elements. In particular, addition of Fe(3+) within a certain concentration range to the growth medium of the preinoculum culture improved the reproducibility and reduced the variance of the bioassay. In contrast, trace elements and vitamins introduced directly into the bioassay caused inhibitory effects. The initial density and luminescence of the sensor strain are very important and the values required for these parameters were defined. Borate interferes with the detection of AI-2 by giving false positive results. The response of V. harveyi BB170 to chemically synthesized AI-2 in the bioassay is nonlinear except over a very small concentration range; it is maximum over three orders of magnitude and shows inhibition above 35 microM. Based on the modified protocol, we were able to detect AI-2 in the absence of inhibitors with maximum fold induction values for the positive control (chemically synthesized AI-2) of >120 with a standard deviation of approximately 30% in a reliable and reproducible way.

Bacteria↗

PubMed2006

Absolute configuration of the creatonotines and callimorphines, two classes of arctiid-specific pyrrolizidine alkaloids.

Arctiids which as larvae sequester pyrrolizidine alkaloids (PAs) from their food plants are known to synthesize insect-specific PAs by esterifying necine bases derived from plant PAs with necic acids of insect origin. There are two classes of insect PAs, the creatonotines and the callimorphines. The creatonotines contain as necic acids either 2-hydroxy-3-methylbutyric acid (creatonotine A) or 2-hydroxy-3-methylpentanoic acid (creatonotine B). The three known callimorphines contain 2-hydroxy-2-methylbutanoic acid whose hydroxyl group can be either free (deacetylcallimorphine) or acetylated (callimorphine) or propionylated (homocallimorphine). Insect PAs are assumed to play an important role in the recycling of plant derived necine bases and the processing by trans-esterification of PA monoesters that cannot be directly transmitted to the insect's pupal and adult life-stages. The absolute configuration of the insect-specific necic acids was elucidated in the context of the suggested role of the insect PAs as insect-made mimics of plant monoester PAs of the lycopsamine type. For this purpose all needed stereoisomers were synthesized and a gas chromatography-mass spectrometry (GC-MS) method was established that allows the enantioselective separation and assignment of the stereochemistry of all insect specific necic acids as their methyl esters. The method could also be applied to the GC-MS analysis of the intact alkaloids which were hydrolyzed during injection and converted into their methyl esters. Analysis of the creatonotines and callimorphines isolated from the polyphagous arctiids Estigmene acrea and Grammia geneura that were fed with pure PAs and defined PA mixtures revealed the following absolute configuration: the callimorphines and creatonotine A were present in 2'R configuration, whereas creatonotine B was found as mixture of (2'R, 3'S)- and (2'S, 3'S)-stereoisomers. The ratio of 2'S to 2'R was extremely variable ranging from 98% S to 94% R. The cause of the lack of stereospecificity is discussed particularly in respect of a possible epimerization of the hydroxyl group at C-2' in analogy to the known epimerization at C-3' of plant acquired PAs of the lycopsamine type.

Animals↗

PubMed2006

Immunofluorescent identification of neuropeptide B-containing nerve fibers and terminals in the rat hypothalamus.

Neuropeptide B (NPB) and the structurally related neuropeptide W (NPW) have recently been identified as the endogenous ligands of the orphan G protein-coupled receptors GPR7 and GPR8. Whereas NPW is a high-affinity ligand for both GPR7 and GPR8, NPB activates only GPR7 in sub-nanomolar concentrations. GPR7 is highly conserved in both human and rodent orthologs while GPR8 has not been found in rodents. GPR7 mRNA is expressed in discrete regions of the hypothalamus suggesting a role in the regulation of energy homeostasis and neuroendocrine axes. In the present study, we have generated and extensively characterized antibodies that exert selective specificity for NPB. In dot-blot assays, these antibodies detected NPB but not NPW. Immunofluorescent staining of rat brain sections revealed moderately dense plexus of NPB-immunoreactive fibers and terminals in discrete areas of the hypothalamus. Neuronal somata were only seen in colchicine-treated rats. This immunostaining was completely abolished by preincubation of the antibodies with NPB but not with NPW. NPB-immunoreactivity was enriched in many regions within the hypothalamus which also contained high levels of GPR7 mRNA including the ventromedial hypothalamic nucleus, dorsomedial hypothalamic nucleus, arcuate nucleus, supraoptic retrochiasmatic nucleus, and in the area ventral to the zona incerta. Together, NPB and its receptor GPR7 exist in close proximity in the rat hypothalamus and are, hence, ideally positioned to modulate neuroendocrine functions.

Animals↗

PubMed2006

Pain control by CXCR2 ligands through Ca2+-regulated release of opioid peptides from polymorphonuclear cells.

Leukocytes counteract inflammatory pain by releasing opioid peptides, which bind to opioid receptors on peripheral sensory neurons. In the early phase of inflammation, polymorphonuclear cells (PMN) are the major source of opioids. Their recruitment is governed by ligands at the chemokine receptor CXCR2. Here, we examined whether chemokines can also induce opioid peptide secretion from PMN and thus inhibit inflammatory pain. In rats with hindpaw inflammation, intraplantar injection of CXCL2/3, but not of the CXCR4 ligand CXCL12, elicited naloxone-reversible (i.e., opioid receptor mediated) mechanical and thermal analgesia, which was abolished by systemic PMN depletion. Both CXCR1/2- and CXCR4-ligands induced PMN chemotaxis, but only CXCR1/2 ligands triggered opioid release from human and rat PMN in vitro. This release was unaltered by extracellular Ca2+ chelation, was mimicked by thapsigargin and was blocked by inhibitors of the inositol 1,4,5-triphosphate receptor (IP3) and by intracellular Ca2+ chelation, indicating that it required Ca2+ from intracellular but not extracellular sources. Furthermore, release was partially reduced by phosphoinositol-3-kinase (PI3K) inhibitors. Adoptive transfer of allogenic PMN into PMN-depleted rats reconstituted CXCL2/3-induced analgesia, which was inhibited by prior ex vivo chelation of intracellular Ca2+. These findings demonstrate that, beyond cell recruitment, CXCR2 ligands induce Ca2+-regulated opioid release from PMN and thereby inhibit inflammatory pain in vivo.

Analgesics↗

PubMed2006

Novel iso-branched ether lipids as specific markers of developmental sporulation in the myxobacterium Myxococcus xanthus.

Iso-fatty acids (FAs) are the dominant FA family in all myxobacteria analyzed. Furthermore, it was postulated that iso-FAs or compounds derived thereof are involved in fruiting body formation in Myxococcus xanthus, since mutants with a reduced level of iso-FA due to a reduced level of the precursor isovaleryl-CoA, are delayed in aggregation and produce only few myxospores. To elucidate the function of iso-FAs and their corresponding lipids we have analyzed the developmental phenotype of mutants having different levels of iso-FAs resulting in a clear correlation between the amount of iso-FAs and the delay of aggregation and reduction in spore yield. Addition of either isovalerate or 13-methyltetradecanoic acid resulted in restoration of the wild-type FA profile and normal development. Detailed analysis of the fatty acid (FA) profile during fruiting body formation in Myxococcus xanthus wild-type revealed the specific accumulation of 13-methyltetradecanal and 1-O-13-methyltetradecylglycerol which were produced specifically in the myxospores and which are derived from 1-O-(13-methyl-1-Z-tetradecenyl)-2-O-(13-methyltetradecanoyl)-glycero-3-phosphatidylethanolamine (VEPE) and 1,2-di-(13-methyltetradecanoyl)-3-(13-methyltetradecyl)glycerol (TG-1), respectively. The structures of these unusual ether lipids have been determined by spectrometric methods and synthesis (for TG-1). Analysis of several mutants blocked at different stages of development indicated that the biosynthesis of TG-1 is developmentally regulated and that VEPE might be an intermediate in the TG-1 biosynthesis. Finally, addition of TG-1 to mutants blocked in the biosynthesis of isovaleryl-CoA could restore aggregation and sporulation emphasizing the important role of iso-branched lipids for myxobacterial development.

Chromatography, High Pressure Liquid↗

PubMed2006

Immunohistochemical detection of bombesin receptor subtypes GRP-R and BRS-3 in human tumors using novel antipeptide antibodies.

Bombesin (BN)-like peptides can stimulate cancer cell growth through binding to their specific G protein-coupled receptors. It is well established that BN receptors are being overexpressed in a subset of human tumors; however, little is known about the cellular and subcellular localization of individual BN receptor subtypes in these tissues. In this study, we developed and characterized novel antipeptide antibodies to the carboxy terminal regions of the gastrin-releasing peptide-preferring bombesin receptor (GRP-R) and the bombesin receptor subtype-3 (BRS-3). Specificity of the antisera was demonstrated by (1) detection of broad bands migrating at Mr 50,000-70,000 in Western blots of membranes from receptor-expressing tissues; (2) cell surface staining of transfected cells; (3) translocation of GRP-R receptor immunostaining after BN exposure; and (4) abolition of tissue immunostaining by preadsorbtion of the antibodies with their immunizing peptides. The distribution of BN receptors was investigated in 74 formalin-fixed, paraffin-embedded human tumors. GRP-R receptors were most frequently detected in breast and prostate carcinomas. BRS-3 receptors were often detected in prostate and pancreatic carcinomas and in pituitary adenomas. Immunoreactive GRP-R and BRS-3 receptors were in many cases predominantly confined to the plasma membrane and uniformly present on nearly all tumor cells. The development of these novel antipeptide antibodies will facilitate the identification of those tumors, which may be targets for diagnostic or radiotherapeutic application of subtype-selective BN analogs.

Amino Acid Sequence↗

PubMed2006

Immunocytochemical localisation of plasma membrane GHRH receptors in human tumours using a novel anti-peptide antibody.

Antagonists of growth hormone releasing hormone (GHRH) directly inhibit the growth of a variety of human neoplasms. However, the plasma membrane receptor mediating these effects has not been immunocytochemically visualised in primary tumour cells. Given that previous attempts using an antibody to the amino-terminal region did not result in the visualisation of plasma membrane receptors, we have developed and characterised an anti-peptide antibody to the carboxy-terminal region 403-422 of the human pituitary GHRH receptor. This sequence is identical to residues 339-358 of splice variant 1 (SV1) of tumoural GHRH receptors. Specificity of the antibody was demonstrated by (1) immunocytochemical staining of GHRH receptor-transfected cells, (2) detection of a broad glycosylated protein band migrating at Mr 50,000-60,000 in Western blots of membranes from human pituitary, and (3) abolition of tissue immunostaining by preadsorbtion of the antibody with its immunising peptide. The distribution of GHRH receptors was investigated in 69 formalin-fixed, paraffin-embedded human tumours showing that GHRH receptors were frequently expressed in breast, ovarian and prostate carcinomas. Immunoreactive GHRH receptors were clearly confined to the plasma membrane and uniformly present on nearly all tumour cells. In Western blots of membranes prepared from human tumours, the anti-GHRH receptor antibody detected a non-glycosylated protein band migrating at Mr 40,000, which corresponds to the expected molecular weight of splice variant 1 of tumoural GHRH receptors. Together, our findings provide direct evidence for the presence of GHRH receptor protein on the plasma membrane of primary human tumour cells. The GHRH receptor visualisation could be of value for a rapid immunohistochemical identification of those tumours which could be a target for diagnostic or therapeutic intervention using GHRH analogues.

Antibodies↗

PubMed2006

Automatic lexeme acquisition for a multilingual medical subword thesaurus.

PURPOSE: We present a method for the automated acquisition of a multilingual medical lexicon (for Spanish, French and Swedish) to be used within the framework of a medical cross-language text retrieval system. METHODS: For the lexical acquisition process, we incorporate seed lexicons and lists of trusted term translations derived from the UMLS Metathesaurus. The seed lexicons for Spanish, French and Swedish are automatically generated from (previously manually constructed) Portuguese, German and English sources by simple string transformations. Lexical and semantic hypotheses are then validated by processing pairs of term translations. In a last step, we use the cleaned list of "approved" translations in order to augment, step by step, the target dictionaries by processing the parallel corpora in terms of co-occurrence patterns of hypothesized translation equivalents which cannot be derived by simple character substitutions. RESULTS: An existing multilingual lexicon for the medical domain with about 60,000 entries for English, German, and Portuguese was automatically augmented by more then 17,000 new lexemes for Spanish, French, and Swedish. CONCLUSIONS: Our approach constitutes a promising method for the automated creation of new lexicon entries and their linkage to semantic identifiers.

Electronic Data Processing↗

PubMed2006

Immunolocalization of full-length NK1 tachykinin receptors in human tumors.

Biological effects of substance P (SP) are mediated by the neurokinin-1 (NK1) receptor that exists as a full-length and as a carboxy-terminally truncated isoform in humans. Although NK1 receptor mRNA and binding sites have been detected in certain malignancies, little is known about the cellular and subcellular localization of NK1 receptor protein in human neoplastic tissues. We developed and characterized a novel anti-peptide antibody to the carboxy-terminal region of the human full-length NK1 receptor. Specificity of the antiserum was demonstrated by (1) detection of a broad band migrating at molecular mass 70,000-90,000 Da in Western blots of membranes from NK1-expressing tissues; (2) cell-surface staining of NK1-transfected cells; (3) translocation of NK1 receptor immunostaining after SP exposure; and (4) abolition of tissue immunostaining by preadsorption of the antibody with its immunizing peptide. Distribution of NK1 receptors was investigated in 72 formalin-fixed, paraffin-embedded human tumors showing that NK1 receptors were frequently expressed in glioblastomas and breast and pancreatic carcinomas. Immunoreactive NK1 receptors were clearly confined to the plasma membrane and uniformly present on nearly all tumor cells. Development of this novel NK1 receptor antibody allows the efficient localization of NK1 receptor protein in human formalin-fixed, paraffin-embedded tissues. NK1 receptor visualization with this simple and rapid immunohistochemical method will facilitate identification of tumors with a sufficient receptor overexpression for diagnostic or therapeutic intervention using SP analogs.

Antibodies↗

PubMed2006

Gastrointestinal cancer web sites: how do they address patients' concerns?

BACKGROUND: We studied the quality of web sites containing information on gastrointestinal cancer, focusing on the way these web sites dealt with the special concerns of these patients. MATERIALS AND METHODS: Searching the Internet for German-language gastroenterological cancer web sites, we collected 9,947 web pages from 14 search engines. Evaluation was done with a 36-item questionnaire. Information quality, availability of the web sites, and web site attributes considering patients' concerns and potential embarrassment were analyzed using a scoring system. RESULTS: Belonging to 165 web sites, 1,763 of 9,947 (17.7%) web pages found by search engines provided relevant information. Five hundred forty-seven (5.5%) hits were partly relevant, and 7,637 (76.8%) were irrelevant or not available. Most web sites reported about surgery (92.1%), chemotherapy (88.5%), and radiotherapy (73.9%). Of the web sites, 46.7% (n=77), 34.6% (n=57), and 21.8% (n=36) gave information about the author(s) itself, their qualifications, and references of their information, respectively. Search engines ranked web sites giving no information on evidence-based medicine higher than other web sites, whereas web sites providing this information accurately showed higher link popularities. Patients' concerns and potential embarrassment were best addressed by gastrointestinal web sites initiated by private individuals or web sites directed to both a patient and physician audience. CONCLUSIONS: With regard to gastrointestinal cancer web sites, many search engines may be ineffective, and patient emotional needs and concerns are often disregarded. Also, physicians should guide their patients through the Internet to find high-quality information and use link-popularity-based search strategies.

Gastrointestinal Neoplasms↗

PubMed2006

Cluster analysis as selection and dereplication tool for the identification of new natural compounds from large sample sets.

Cluster analysis of gas-chromatographic (GC) data of ca. 500 bacterial isolates was used as an aid in detection and identification of new natural compounds. This approach reduces the number of GC/MS analysis (dereplication) and concomitantly improves the selection of samples with high probability to contain unknown natural products. Lipophilic bacterial extracts were derivatized and analyzed by GC under standardized conditions. A program was developed to convert chromatographic data into a two-dimensional matrix. Based on the results of hierarchical cluster analysis samples were selected for further investigation by GC/MS and NMR. This approach avoided unnecessary analysis of similar samples. By this method, the unusual oligoprenylsesquiterpenes 1 and 2 as well as new aromatic amides 7 and 8 were identified.

Bacteria↗

PubMed2006

Design, synthesis, and biological evaluation of somatostatin-based radiopeptides.

The prototypes for tumor targeting with radiolabeled peptides are derivatives of somatostatin. Usually, they primarily have high affinity for somatostatin receptor subtype 2 (sst2), and they have moderate affinity for sst5. We aimed at developing analogs that recognize different somatostatin receptor subtypes for internal radiotherapy in order to extend the present range of accessible tumors. We synthesized DOTA-octapeptides based on octreotide by replacing Phe3 mainly with unnatural amino acids. The affinity profile was determined by using cell lines transfected with sst1-5. Internalization was determined by using AR42J, HEK-sst3, and HEK-sst5 cell lines, and biodistribution was studied in rat tumor models. Two of the derivatives thus obtained showed an improved binding affinity profile, enhanced internalization into cells expressing sst2 and sst3, respectively, and better tumor:kidney ratios in animals.

Animals↗

PubMed2006

Ethyl-branched aldehydes, ketones, and diketones from caimans (Caiman and Paleosuchus; Crocodylia, Reptilia).

Secretions from the paracloacal glands of alligators (Alligator spp.) and caimans (Caiman spp., Melanosuchus niger, and Paleosuchus spp.) were examined by GC-MS. The secretions of the common caiman (C. crocodilus), the broad-snouted caiman (C. latirostris), the yacare caiman (C. yacare), the dwarf caiman (P. palpebrosus), and the smooth-fronted caiman (P. trigonatus) yielded a new family of 43 aliphatic carbonyl compounds that includes aldehydes, ketones, and beta-diketones with an ethyl branch adjacent to the carbonyl group. The identification of these glandular components and the syntheses and stereochemical investigations of selected compounds are described.

Aldehydes↗

PubMed2006

Immunocytochemical identification of low-affinity NTS2 neurotensin receptors in parietal cells of human gastric mucosa.

The biological effects of neurotensin (NT) are mediated by two distinct G protein-coupled receptors, NTS(1) and NTS(2). Although it is well established that neurotensin inhibits gastric acid secretion in man, the plasma membrane receptor mediating these effects has not been visualized yet. We developed and characterized a novel antipeptide antibody to the carboxy-terminal region of the human NTS(2) receptor. The cellular and subcellular distribution of NTS(2) receptors was evaluated in various human gastrointestinal tissues. Specificity of the antiserum was demonstrated by (1) detection of a broadband migrating at M(r) 90 000-100 000 in Western blots of membranes from NTS(2)-expressing tissues; (2) cell-surface staining of NTS(2)-transfected cells; (3) translocation of NTS(2) receptor immunostaining after agonist exposure; and (4) abolition of tissue immunostaining by preadsorbtion of the antibody with its immunizing peptide. In the gastrointestinal tract, NTS(2) receptor immunoreactivity was highly abundant in parietal cells of the gastric mucosa, in neuroendocrine cells of the stomach small and large intestine, and in cells of the exocrine pancreas. NTS(2) receptors were clearly located in the plasma membrane and uniformly present on nearly all target cells. The presence of NTS(2) receptors was rarely detected in human tumors. This is the first localization of NTS(2) receptors in human formalin-fixed, paraffin-embedded tissues at the cellular level. The abundant expression of low-affinity NTS(2) receptors on the plasma membrane of human parietal cells provides a morphological substrate for the direct inhibition of gastric acid secretion observed after i.v. administration of neurotensin.

Antibodies, Monoclonal↗

PubMed2006

Internalization of sst2, sst3, and sst5 receptors: effects of somatostatin agonists and antagonists.

UNLABELLED: The uptake of radiolabeled somatostatin analogs by tumor cells through receptor-mediated internalization is a critical process for the in vivo targeting of tumoral somatostatin receptors. In the present study, the somatostatin receptor internalization induced by a variety of somatostatin analogs was measured with new immunocytochemical methods that allow characterization of trafficking of the somatostatin receptor subtype 2 (sst2), somatostatin receptor subtype 3 (sst3), and somatostatin receptor subtype 5 (sst5) in vitro at the protein level. METHODS: Human embryonic kidney 293 (HEK293) cells expressing the sst2, sst3, or the sst5 were used in a morphologic immunocytochemical internalization assay using specific sst2, sst3 and sst5 antibodies to qualitatively and quantitatively determine the capability of somatostatin agonists or antagonists to induce somatostatin receptor internalization. In addition, the internalization properties of a selection of these agonists have been compared and quantified in sst2-expressing CHO-K1 cells using an ELISA. RESULTS: Agonists with a high sst2-binding affinity were able to induce sst2 internalization in the HEK293 and CHO-K1 cell lines. New sst2 agonists, such as Y-DOTA-TATE, Y-DOTA-NOC, Lu-DOTA-BOC-ATE (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; TATE is [Tyr3, Thr8]-octreotide; NOC is [1-NaI3]-octreotide; and BOC-ATE is [BzThi3, Thr8]-octreotide), iodinated sugar-containing octreotide analogs, or BIM-23244 were considerably more potent in internalizing sst2 than was DTPA-octreotide (where DTPA is diethylenetriaminepentaacetic acid). Similarly, compounds with high sst3 affinity such as KE108 were able to induce sst3 internalization. In sst2- or sst3-expressing cell lines, agonist-induced receptor internalization was efficiently abolished by sst2- or sst3-selective antagonists, respectively. Antagonists alone had no effect on sst2 or sst3 internalization. We also showed that somatostatin-28 and somatostatin-14 can induce sst5 internalization. Unexpectedly, however, potent sst5 agonists such as KE108, BIM-23244, and L-817,818 were not able to induce sst5 internalization under the same conditions. CONCLUSION: Using sensitive and reproducible immunocytochemical methods, the ability of various somatostatin analogs to induce sst2, sst3, and sst5 internalization has been qualitatively and quantitatively determined. Whereas all agonists triggered sst2 and sst3 internalization, sst5 internalization was induced by natural somatostatin peptides but not by synthetic high-affinity sst5 agonists. Such assays will be of considerable help for the future characterization of ligands foreseen for nuclear medicine applications.

Animals↗

PubMed2006

Comparison of ICHI and CCAM basic coding system.

While diagnoses are coded by ICD across the world, there is no universally accepted coding system for procedures. In many countries there exists not even a local classification for medical procedures. As a possible solution the International Classification of Health Interventions (ICHI) has been proposed as a common denominator for an international procedure classification. We alternatively postulate a multiaxial framework for procedure classification following the French Classification Commune des Actes Médicaux (CCAM) for the generation of a procedure shortlist. We compared ICHI and CCAM Basic Coding System focusing on the appropriateness of both systems for supporting the comparability of procedure data. Considering the ongoing standardization of health terminologies and classifications, we strongly recommend to improve the ICHI structure, capitalizing on the benefits of the CCAM architecture.

Forms and Records Control↗

PubMed2006

An Ontology driven collaborative development for biomedical terminologies: from the French CCAM to the Australian ICHI coding system.

The CCAM French coding system of clinical procedures was developed between 1994 and 2004 using, in parallel, a traditional domain expert's consensus method on one hand, and advanced methodologies of ontology driven semantic representation and multilingual generation on the other hand. These advanced methodologies were applied under the framework of an European Union collaborative research project named GALEN and produced a new generation of biomedical terminology. Following the interest in several countries and in WHO, the GALEN network has tested the application of the ontology driven tools to the existing reduced Australian ICHI coding system for interventions presently under investigation by WHO to check its ability and appropriateness to become the reference international coding system for procedures. The initial results are presented and discussed in terms of feasibility and quality assurance for sharing and maintaining consistent medical knowledge and allowing diversity in linguistic expressiveness of end users.

Australia↗

PubMed2005

Biomedical ontologies: what part-of is and isn't.

Mereological relations such as part-of and its inverse has-part are fundamental to the description of the structure of living organisms. Whereas classical mereology focuses on individual entities, mereological relations in biomedical ontologies are generally asserted between classes of individuals. In general, this practice leaves some basic issues unanswered: type constraints of mereological relations, e.g., concerning artifacts and biological entities, the relation between parthood and time, inferred parts and wholes as well as a delimitation of parthood against spatial inclusion. Furthermore, mereological relations can be asserted not only between physical objects but also between biological processes and medical procedures. We analyze these ambiguities and make suggestions for a standardization of mereological relations in biomedical ontologies.

Anatomy↗