Identification of bacterial species by untargeted NMR spectroscopy of the exo-metabolome.

Identification of bacterial species is a crucial bottleneck for clinical diagnosis of infectious diseases. Quick and reliable identification is a key factor to provide suitable antibiotherapies and avoid the development of multiple-drug resistance. We propose a novel nuclear magnetic resonance (NMR)-based metabolomics strategy for rapid discrimination and identification of several bacterial species that relies on untargeted metabolic profiling of supernatants from bacterial culture media. We show that six bacterial species (Gram negative: Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis; Gram positive: Enterococcus faecalis, Staphylococcus aureus, and Staphylococcus saprophyticus) can be well discriminated from multivariate statistical analysis, opening new prospects for NMR applications to microbial clinical diagnosis.

European proficiency study with control serum for the tumor marker CA 19-9 measured on different test systems.

BACKGROUND: Reliable and precise CA 19-9 testing is required for the long-term follow-up of patients with pancreatic carcinoma during therapy. The aim of this longitudinal proficiency study was to evaluate the comparability, linearity, and precision of CA 19-9 determinations performed in different laboratories using currently available test systems under routine conditions. METHODS: During the one year study period, 15 laboratories applied 7 different tests and included a liquid BIOREF control serum with pancreatic carcinoma derived CA 19-9 in their routine testing and quality control procedures. The results were collected centrally and evaluated statistically. RESULTS: The comparability of CA 19-9 results is limited especially when different tests are used, albeit, some tests show a good correlation: The CA 19-9 values obtained by different laboratories using different test systems vary up to a factor of 2. The precision of CA 19-9 determinations was acceptable in most laboratories with coefficients of variation ranging between very low 3.2% and high 17.8%. The imprecision was slightly increased when automatic dilution procedures of the analysers were used. CONCLUSIONS: The comparability of CA 19-9 test results must be improved. The precision is acceptable in most cases. In order to monitor key performance parameters, every laboratory should participate in external quality assessment schemes and should perform a routine internal quality control with a control serum independent from the test kit manufacturer.

Unusual increase of psittacosis in southern Sweden linked to wild bird exposure, January to April 2013.

Free-living wild birds worldwide act as reservoir for Chlamydia psittaci, but the risk of transmission to humans through contact with wild birds has not been widely documented. From 12 January to April 9 2013, a total of 25 cases of psittacosis were detected in southern Sweden, about a threefold increase compared with the mean of the previous 10 years. A matched case-control study investigating both domestic and wild bird exposure showed that cases were more likely than controls to have cleaned wild bird feeders or been exposed to wild bird droppings in other ways (OR: 10.1; 95% CI: 2.1-47.9). We recommend precautionary measures such as wetting bird feeders before cleaning them, to reduce the risk of transmission of C. psittaci when in contact with bird droppings. Furthermore, C. psittaci should be considered for inclusion in laboratory diagnostic routines when analysing samples from patients with atypical pneumonia, since our findings suggest that psittacosis is underdiagnosed.

Pediatric head and neck manifestations associated with multiple endocrine neoplasia syndromes.

INTRODUCTION: Multiple endocrine neoplasia (MEN) syndromes are a group of hereditary cancer syndromes that can predispose children to endocrine neoplasms developing within the head and neck. OBJECTIVE: To examine the neoplastic manifestations of MEN type 1 (MEN1) and MEN type 2 (MEN2) in the pediatric head and neck. METHODS: Single-institution, retrospective review of pediatric MEN between 2005 and 2022. RESULTS: Fifty-three children were genetically confirmed with MEN (15 MEN1, 34 MEN2A, and 4 MEN2B), while three patients received clinical diagnoses of MEN1. The male to female ratio was essentially equal (1.15:1), and a documented family history of cancer was present in 89% (50/56). After multidisciplinary evaluation, a familial MEN diagnosis was confirmed in 91% (51/56). The mean ages of initial presentation and surgical intervention were 8.9 years (SD 5) and 9.8 years (SD 4.8), respectively. Although patients with MEN2 received surgery earlier than patients with MEN1 (8.7 vs 12.7 years), surgical patients with MEN2 in this cohort were older relative to current American Thyroid Association (ATA) guidelines primarily due to late presentation. Thyroid malignancies were identified in 36% (9/25) of thyroidectomy specimens (21 MEN2A, 4 MEN2B), with medullary thyroid carcinoma (MTC) present in five MEN2A patients and three MEN2B patients (89%), and papillary thyroid carcinoma (PTC) present in one MEN2A patient (11%). Nearly 90% (8/9) of thyroid malignancies were occult, with some occurring earlier than predicted by current guidelines (ATA-MOD and ATA-H). Central neck dissections were performed in 24% (2 MEN1, 2 MEN2A, and 4 MEN2B), with two MEN2B (50%) demonstrating cervical lymph node (LN) metastases. Additional histopathologic findings included C-cell hyperplasia in 57% (12/21) of MEN2A thyroidectomy patients. Of the eight MEN1 parathyroidectomy patients, four demonstrated parathyroid hyperplasia and four presented with parathyroid adenoma. CONCLUSION: Nearly 60% required head and neck procedures. While MEN1 guidelines were appropriate for our cohort, we identified patients with MEN2 that developed MTC earlier than expected based on current ATA guidelines, including children in categories considered lower risk. In conjunction with a multidisciplinary approach, pediatric head and neck surgeons should be aware of the potential need for earlier surgical intervention in the pediatric MEN2 population.

[Guidelines and evidence. Recent developments in medical child protection]. / Leitlinien und Evidenz. Neue Entwicklungen im somatischen medizinischen Kinderschutz.

Medical child protection comprises different types of involvement of physicians in order to protect children and adolescents from abuse and neglect. This review gives an overview of historical and recent developments in medical child protection. The professional foundation of medical involvement in this field requires a debate on the following questions: Is there evidence for the diagnostic criteria of child abuse and neglect? How far are the principles of evidence-based medicine applicable to the development of guidelines in child protection?

The NH2 terminus of titin spans the Z-disc: its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity.

Titin is a giant elastic protein in vertebrate striated muscles with an unprecedented molecular mass of 3-4 megadaltons. Single molecules of titin extend from the Z-line to the M-line. Here, we define the molecular layout of titin within the Z-line; the most NH2-terminal 30 kD of titin is located at the periphery of the Z-line at the border of the adjacent sarcomere, whereas the subsequent 60 kD of titin spans the entire width of the Z-line. In vitro binding studies reveal that mammalian titins have at least four potential binding sites for alpha-actinin within their Z-line spanning region. Titin filaments may specify Z-line width and internal structure by varying the length of their NH2-terminal overlap and number of alpha-actinin binding sites that serve to cross-link the titin and thin filaments. Furthermore, we demonstrate that the NH2-terminal titin Ig repeats Z1 and Z2 in the periphery of the Z-line bind to a novel 19-kD protein, referred to as titin-cap. Using dominant-negative approaches in cardiac myocytes, both the titin Z1-Z2 domains and titin-cap are shown to be required for the structural integrity of sarcomeres, suggesting that their interaction is critical in titin filament-regulated sarcomeric assembly.

In vivo proliferation of rat lamina propria T lymphocytes: general hyporesponsiveness but increased importance of the CD2 and CD28 pathways.

Lamina propria T lymphocytes (LPL-T) have a low proliferative potential in vitro. We asked whether LPL-T are also hyporesponsive in vivo and whether this is specific for the alphabeta T cell receptor (TCR). Mitogenic mAb directed at the alphabeta TCR, CD2, CD28, or control mAbs plus IL-2 were injected into rats. Proliferation and/or apoptosis were detected by double staining using 5-bromo-2'-deoxyuridine/TUNEL and the alphabeta TCR. LPL-T were hyporesponsive to various stimuli compared to other T cells. The strongest proliferation was found upon CD2/CD28 stimulation (LPL-T: 281 +/- 6%; spleen: 642 +/- 31%). LPL-T proliferation was only detectable at 24 h while proliferation in other compartments also occurred later. Hyporesponsiveness was not caused by enhanced T cell apoptosis upon alphabeta TCR stimulation. In conclusion, stimulation of LPL-T results in much shorter and weaker in vivo proliferation than in other lymphoid organs. Overall, CD2/CD28 costimulation is the strongest T cell stimulus in vivo.

Waterborne and diet-related effects of inorganic and organic fungicides on the insect leaf shredder Chaetopteryx villosa (Trichoptera).

It is well-documented that fungicides can affect crustacean leaf shredders via two effect pathways, namely waterborne exposure and their diet (i.e., via dietary uptake of fungicides adsorbed to leaf material and an altered microorganism-mediated food quality). As a consequence of different life history strategies, the relevance of these effect pathways for aquatic shredders belonging to other taxonomic classes, for instance insects, remains unclear. Therefore, we investigated waterborne and diet-related effects in larvae of the caddisfly leaf shredder Chaetopteryx villosa (Insecta: Trichoptera) and compared our observations to previous reports on effects in adults of the crustacean leaf shredder Gammarus fossarum (Malacostraca: Amphipoda). We assessed acute waterborne effects of an organic fungicide mixture (OFM) and the inorganic fungicide copper (Cu) on the leaf consumption (n = 30) of the fourth-/fifth-instar larvae of C. villosa and their food choice (n = 49) when offered leaf material, which was either conditioned in presence or in absence of the respective fungicide(s). Moreover, the larval leaf consumption (n = 50) and physiological fitness (i.e., growth as well as lipid and protein content) were examined after subjecting C. villosa for 24 days towards the combination of both effect pathways at environmentally relevant concentrations. G. fossarum and C. villosa exhibited similar sensitivities and the same effect direction when exposed to the OFM (either waterborne or dietary pathways). Both shredders also showed the same effect direction when exposed to dietary Cu, while with regards to mortality and leaf consumption C. villosa was less sensitive to waterborne Cu than G. fossarum. Finally, as observed for G. fossarum, the combined exposure to OFM over 24 days negatively affected leaf consumption and the physiology (i.e., growth and lipid reserves) of C. villosa. While no combined Cu effects were observed for larval leaf consumption, contrasting to the observations for G. fossarum, the physiology of both shredders was negatively affected, despite partly differing effect sizes and directions. Our results suggest that C. villosa and G. fossarum are of comparable sensitivity towards waterborne and diet-related organic fungicide exposure, whereas the trichopteran is less sensitive to Cu-based waterborne fungicide exposure. However, when both pathways act jointly, organic and inorganic fungicides can affect the physiology of shredder species with completely different life history strategies. As caddisflies represent a subsidy for terrestrial consumers, these observations indicate that fungicide exposure might not only affect aquatic ecosystem functioning but also the flux of energy across ecosystem boundaries.

Chlamydia trachomatis genotypes A and B from urogenital specimens of patients in Spain: molecular characterization.

OBJECTIVES: Chlamydia trachomatis ompA genotypes A and B, primarily associated with trachoma, were unexpectedly detected in urogenital samples of patients in Spain, a trachoma-free country. In this study, we aimed to explain this finding using analysis of organotropism-related genes and a multilocus sequence typing (MLST) technique. METHODS: C. trachomatis genotypes A or B were detected in 8/930 (0.9%) infection episodes between 2006 and 2012. In these strains, organotropism-related genes (polymorphic membrane protein gene H, tryptophan synthase gene A, CTA0934, and cytotoxin) were studied. Further, the strains were analysed by MLST, using a polymerase chain reaction that amplifies five highly variable genomic loci (hctB, CT058, CT144, CT172, and pbpB). Amplicons were sequenced and phylogenetic analysis was conducted. RESULTS: Seven strains were detected in the eight infection episodes (in one patient, an identical strain being found in two episodes). Analysis of organotropism-related genes showed that these strains shared genetic features characteristic of genitotropic genotypes but not of trachoma strains. Three strains of genotype A showed a unique and new MLST-sequence type (ST551, allele profile 8-8-2-27-69). The four strains of genotype B belonged to ST138. CONCLUSIONS: C. trachomatis ompA genotypes A and B associated with trachoma, but detected sporadically in urogenital samples in trachoma-free countries, may be the result of recombination between strains adapted to trachoma and strains adapted to sexual transmission.

The T genes in embryogenesis.

Since its identification in 1927, the mouse T (Brachyury) locus has been implicated in mesoderm formation and notochord differentiation. Recent work has demonstrated that this gene encodes a putative transcription factor expressed specifically in nascent mesoderm and in the differentiating notochord. Homologous genes have been cloned from the frog Xenopus laevis, the zebrafish Brachydanio rerio and the ascidian Halocynthia roretzi. The T gene is an important tool for elucidating mesoderman and embryonic pattern formation.

Challenges in quantifying biosphere-atmosphere exchange of nitrogen species.

Recent research in nitrogen exchange with the atmosphere has separated research communities according to N form. The integrated perspective needed to quantify the net effect of N on greenhouse-gas balance is being addressed by the NitroEurope Integrated Project (NEU). Recent advances have depended on improved methodologies, while ongoing challenges include gas-aerosol interactions, organic nitrogen and N(2) fluxes. The NEU strategy applies a 3-tier Flux Network together with a Manipulation Network of global-change experiments, linked by common protocols to facilitate model application. Substantial progress has been made in modelling N fluxes, especially for N(2)O, NO and bi-directional NH(3) exchange. Landscape analysis represents an emerging challenge to address the spatial interactions between farms, fields, ecosystems, catchments and air dispersion/deposition. European up-scaling of N fluxes is highly uncertain and a key priority is for better data on agricultural practices. Finally, attention is needed to develop N flux verification procedures to assess compliance with international protocols.

Experiences with the new genetic variant of Chlamydia trachomatis in Orebro county, Sweden - proportion, characteristics and effective diagnostic solution in an emergent situation.

A Chlamydia trachomatis variant that contains a 377 bp deletion in the cryptic plasmid was recently reported in Sweden. This deletion includes the targets for Cobas Amplicor, Cobas TaqMan48, and Abbott m2000. We examined the proportion and characteristics of this variant in Orebro county, Sweden and developed an effective diagnostic solution. In total, 2,401 consecutive C. trachomatis culture samples and 536 PCR samples from symptomatic and asymptomatic patients and screened females were included. Culture, Cobas Amplicor, and LightMix 480HT were used for diagnosis. A mutant-specific PCR, plasmid sequencing, omp1 sequencing and multilocus sequence typing (MLST) were used to identify and characterise mutants. In total, 162 (6.7%) of the cultured samples were positive for C. trachomatis. However, 61 (38%) of those were negative when using Cobas Amplicor, and 60 of these were subsequently confirmed as the new variant. 13 of these mutant isolates were further characterised genetically, and all were of identical genotype E and the unique MLST sequence type: 21, 19, 1, 2, 1. Of all culture-positive samples, 161 of 162 were positive in the LightMix 480HT assay. The single negative sample was only weakly positive in culture, and negative in all PCRs. Of the 536 PCR samples, 37 were positive in both Cobas Amplicor and LightMix 480HT, 13 were only positive in LightMix 480HT (mutants), and two were only positive in Cobas Amplicor. Mutated C. trachomatis were prevalent in Orebro county in the period from October 2006 to February 2007, and it appeared to be a single clone. LightMix 480HT seemed sensitive, specific, and enabled high throughput diagnostics. However, rare low positive samples may be false-negative. Frequent surveillance and evaluations of diagnostic methods worldwide are crucial.

First case of human bacteraemia by Catabacter hongkongensis in Scandinavia.

Catabacter hongkongensis was isolated and cultured from human blood for the first time in Scandinavia. The patient, an 83-year-old man from Dalarna, Sweden, recovered without antibiotic treatment, although a high mortality rate associated with C. hongkongensis infection had been reported from China, Canada and France. The genome of the strain ABBA15k was sequenced, assembled and analysed. In contrast to the type strain of the species HKU16T, no antibiotic resistance was observed in Scandinavian strain ABBA15k. The strain was deposited as CCUG 68271, and the draft genome sequence is available from the DNA Data Bank of Japan (DDBJ), the European Molecular Biology Laboratory (EMBL), and GenBank under the accession number LLYX00000000.

Discrepant results in the diagnosis of GH deficiency with the insulin-tolerance test and the GHRH plus arginine test in patients with traumatic brain injury.

OBJECTIVE: Patients with traumatic brain injury (TBI) are at moderate risk of GH deficiency (GHD), requiring a diagnostic test with high specificity. The GHRH + arginine (GHRH + ARG) test has been recommended as a reliable alternative to the insulin-tolerance test (ITT) as a standard test with a cutoff level of 9 ng/ml. However, it has recently been questioned for its low specificity in obese subjects, and now BMI-dependent cut-off levels are available. In this study, we compared the ITT and GHRH + ARG test in patients with TBI. DESIGN: A cross-sectional study METHODS: We performed an ITT and a GHRH + ARG test in 21 patients with TBI (6 women, 15 men; mean age 40.2 +/- 12.1 years; BMI 30.7 +/- 6.2). The number of patients classified discordantly as GH deficient by the ITT and the GHRH + ARG test with both classical and BMI-dependent cut-off levels was assessed. RESULTS: Using the GHRH + ARG test with the classical cut-off ( 3 ng/ml), and one patient as GH sufficient who had a blunted GH response to ITT (discordance rate 61.9%). All patients discordantly classified as GH deficient by the GHRH + ARG test had a BMI of >or= 28. With the BMI-dependent cut-offs (4.2, 8.0, and 11.5 ng/ml in obese, overweight, and lean subjects respectively), only 3 of the 21 patients were discordantly classified (discordance rate 14.3%). CONCLUSIONS: Our results discourage the use of a cut-off level of 9 ng/ml for the GHRH + ARG test in obese subjects. The diagnostic reliability of this test is improved with the BMI-dependent cut-offs.

Hypopituitarism following severe traumatic brain injury.

Although hypopituitarism is a known complication of traumatic head injury, it may be under-recognized due to its subtle clinical manifestations. To address this issue, we determine the prevalence of neuroendocrine abnormalities in patients rehabilitating from severe traumatic brain injury (Glasgow Coma Scale < or = 8). 76 patients (mean age 39 +/- 14 yr; range 18-65; 53 males and 23 females; BMI 25.8 +/- 4.2 kg/m2; mean +/- SD) with a severe traumatic brain injury, an average of 22 +/- 10 months before this study (median, 20 months), underwent a series of standard endocrine tests, including TSH, free T4, T4, T3, prolactin, testosterone (males), estradiol (females), cortisol, ACTH, GH, and IGF-I. All subjects also underwent GH response to GHRH + arginine. Growth hormone deficiency (GHD) was defined as a GH response < 9 microg/L to GHRH + arginine and was confirmed by ITT (< 3 microg/L). Pituitary deficiency was shown in 24% of the patients (18/76). 8% (n = 6) had GHD (GH-peak range [GHRH + arginine]: 2.8-6.3 microg/L; GH-peak range [ITT]: 1.5-2.2 microg/L; IGF-I range: 62-174 microg/L). 17% (n = 13) had hypogonadism (total testosterone < 9.5 nmol/L and low gonadotropins in 12 males; low estradiol, and low gonadotropins in 1 female). Total testosterone levels did not correlate with BMI or age. 2 males with hypogonadism also showed a mild hyperprolactinemia (33 and 41 ng/ml). 3% (n = 2) patients had partial ACTH-deficiency (cortisol-peak [ITT] 392 and 417 nmol/L) and 3% (n = 2) had TSH-deficiency. In summary, we have found hypopituitarism in one-fourth of patients with predominantly secondary hypogonadism and GHD. These findings strongly suggest that patients who suffer head trauma must routinely include neuroendocrine evaluations.

Regulated redistribution of calretinins in WiDr cells.

The calcium-binding protein calretinin and the alternatively spliced form calretinin-22k are expressed in the colon adenocarcinoma cell line WiDr. As calcium-binding proteins have been implicated to play a role in cell cycle control, proliferation and differentiation, the levels and intracellular localisation of these two proteins were investigated. The addition of 1,25-dihydroxy vitamin D3 (10(-8) M) led to a transient translocation of calretinin-22k into the nucleus, while the cell growth was not affected. The addition of sodium butyrate and hexamethylene bisacteamide which induce markers of enterocyte differentiation decreased the levels of both forms of calretinin more than 90%. The agents which induced differentiation also led to a substantial inhibition of 3H-thymidine incorporation (>95%) which was paralleled by the disappearance of calretinins. We conclude that calretinin and calretinin-22k are associated with the proliferative status of WiDr cells and are almost completely absent in differentiated cells.

Isolation, characterization and chromosomal mapping of the mouse tyrosine aminotransferase gene.

The tyrosine aminotransferase (TAT) gene is expressed in a tissue and developmental-specific manner. In addition, this gene is regulated by glucocorticoid and polypeptide hormones and its expression is affected when a regulatory region near the albino locus of the mouse is deleted. In order to allow studies of the molecular effects of these deletion mutations we have isolated and characterized the mouse TAT gene. The gene is 9.2 x 10(3) bases in length and consists of 12 exons which give rise to a 2.3 x 10(3) base long messenger RNA. The DNA sequence at the 5' end of the gene was determined and compared with the corresponding sequence of the rat tyrosine aminotransferase gene. The sequence comparison showed extensive homology over the entire region sequenced. In addition, DNA: DNA heteroduplex studies between the mouse and rat tyrosine aminotransferase genes revealed that this homology extends over the entire gene and its flanking sequences. The mouse tyrosine aminotransferase gene has been mapped distal to the serum esterase-1 locus on mouse chromosome 8, using a restriction fragment length polymorphism between two mouse species. Since the albino deletions are located on mouse chromosome 7, the assignment of the TAT gene to chromosome 8 suggests that a regulatory factor(s) affecting TAT gene expression acts in trans.

Genomic organization of M line titin and its tissue-specific expression in two distinct isoforms.

Titin is a 3000 kDa large protein of vertebrate striated muscle which extends from Z discs to M lines. Within the segment of titin that locates in the I band, tissue-specific isoforms are expressed by differential splicing in correlation to the sarcomeric ultrastructure. We have now searched the M-line region of titin for differential expression. The 20 kb section from the 3' end of the gene has been sequenced and contains 23 exons. Exon/intron organization is correlated to the modular organization of the titin protein. The six exons at the 3' end of the gene encode the M-line section of titin and are referred to as Mex1 to Mex6. Analysis of the RNAs expressed in different rabbit striated muscles reveals that the exon Mex5 is either included or excluded in the titin mRNA during splicing. The levels of inclusion of Mex5 vary between different types of striated muscles. Heart expresses (Mex5+)-titin, skeletal muscles co-express tissue-specifically distinct ratios of (Mex5+) and (Mex5-)-titins. In situ hybridization of whole-mount mouse embryos with Mex5 antisense RNA provide no evidence for the exclusion of Mex5 during embryonic development. We speculate that the establishment of differential splicing pathways of M-line titin late during development may correlate with and explain the postnatal development of different M-line fine structures in the different muscles. Comparison of titin gene sequences from different vertebrates reveals that the intron sequences located upstream of Mex3 and Mex5, referred to as Min-2 and Min-4, respectively, have remained strongly conserved during evolution. While the conservation of Min-4 may be explained by its participation in the regulation of the differential skipping of Mex5, the functional significance of the conservation of the Min-2 intron located upstream of Mex3 is yet unknown.

Large-scale screen for genes involved in gonad development.

The vertebrate gonad develops from the intermediate mesoderm as an initially bipotential organ anlage, the genital ridge. In mammals, Sry acts as a genetic switch towards testis development. Sox9 has been shown to act downstream of Sry in testis development, while Dax1 appears to counteract Sry. Few more genes have been implicated in early gonad development. However, the genetic networks controlling early differentiation events in testis and ovary are still far from being understood. In order to provide a broader basis for the molecular analysis of gonad development, high-throughput gene expression analysis was utilized to identify genes specifically expressed in the gonad. In total, among 138 genes isolated which showed tissue specific expression in the embryo, 79 were detected in the developing gonad or sex ducts. Twenty-seven have not been functionally described before, while 40 represent known genes and 12 are putative mouse orthologues. Forty-five of the latter two groups (86%) have not been described previously in the fetal gonad. In addition, 21 of the gonad specific genes showed sex-dimorphic expression suggesting a role in sex determination and/or gonad differentiation. Eighteen of the latter (86%) have not been described previously in the fetal gonad. In total we provide new data on 72 genes which may play a role in gonad or sex duct development and/or sex determination. Thus we have generated a large gene resource for the investigation of these processes, and demonstrate the suitability of high-throughput gene expression screening for the genetic analysis of organogenesis.

Kidney-specific cadherin (cdh16) is expressed in embryonic kidney, lung, and sex ducts.

Cdh16 was initially described as a truncated cadherin expressed in the adult rabbit kidney. We have analyzed the expression pattern of cdh-16 during mouse embryogenesis, and show that cdh-16 transcripts are present in ureter-derived epithelia of the metanephric kidney. In addition, we demonstrate that cdh-16 is also transiently expressed in the epithelia of embryonic sex ducts and the lung of the embryo.