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PubMed1989

Embryonic origins and assembly of blood vessels.

Embryonic blood vessels develop in two ways: angiogenesis, which is growth by budding, branching, and elongation of existing vessels, and in situ formation of endothelial vesicles that coalesce with elongating vessels. It is assumed that the former is more prevalent, with the latter restricted to vessels that form near the endoderm:mesoderm interface. Neither the relative contributions of each of these processes in the formation of specific blood vessels nor the origins of precursors (angioblasts) of these intraembryonic endothelial populations are known. Antibodies that recognize quail endothelial cells can be used to follow the movements and differentiation of endothelial cell precursors after the transplantation of putative precursor populations from quail into chick embryos. Using this method, it has been shown that all intraembryonic mesodermal tissues, except the prechordal plate, contain angiogenic precursors. After transplantation some angioblasts move in all directions away from the site of implantation, invading surrounding mesenchyme and contributing to the formation of arteries, veins, and capillaries in a wide area. Although it is clear that these invasive angioblasts, which behave unlike any other embryonic mesenchymal cell type, are found throughout the embryo, it is not known whether they represent a unique endothelial cell type in mature blood vessels. Irrespective of their original location in the donor embryo, transplanted angioblasts will form vascular channels that are appropriate for the tissues surrounding their site of implantation. These results indicate that the control over vascular assembly resides within the connective-tissue-forming mesenchyme of the embryo.

Animals↗

PubMed1995

X-ray crystal structure of the soybean agglutinin cross-linked with a biantennary analog of the blood group I carbohydrate antigen.

Soybean agglutinin (SBA) (Glycine max), which is a tetrameric GalNAc/Gal-specific lectin, has recently been reported to form unique, highly organized cross-linked complexes with a series of naturally occurring and synthetic multiantennary carbohydrates with terminal GalNAc or Gal residues [Gupta, D., Bhattacharyya, L., Fant, J., Macaluso, F., Sabesan, S., & Brewer, C. F. (1994) Biochemistry 33, 7495-7504]. In order to elucidate the nature of these complexes, the X-ray crystallographic structure of SBA cross-linked with a biantennary analog of the blood group I carbohydrate antigen is reported. The structure reveals that lattice formation is promoted uniquely by the bridging action of the bivalent pentasaccharide (beta-LacNAc)2Gal-beta-R, where R is -O(CH2)5COOCH3 and the beta-LacNAc moieties are linked to the 2 and 6 positions of the core Gal. The structure of SBA complexed with the synthetic biantennary pentasaccharide has thus been determined by molecular replacement techniques and refined at 2.6 A resolution to an R value of 20.1%. The crystals are hexagonal with a P6(4)22 space group, which differs significantly from that of crystals of the free protein. In the structure, each monomeric asymmetric unit contains a Man9 oligomannose-type chain at Asn 75, with only the first two GlcNAc residues visible. The overall tertiary structure of the SBA subunit is similar to that of other legume lectins as well as certain animal lectins. However, the dimer interface in the SBA tetramer is unusual in that only one complete peptide chain is sterically permitted, thus requiring juxtapositioning of one C-terminal fragmented subunit together with an intact subunit. Association between SBA tetramers involves binding of the terminal Gal residues of the pentasaccharide at identical sites in each monomer, with the sugar cross-linking to a symmetry-related neighbor molecule. The cross-linking pentasaccharide is in a conformation that possesses a pseudo-2-fold axis of symmetry which lies on a crystallographic 2-fold axis of symmetry of the lattice. Hence, the symmetry properties of the bivalent oligosaccharide as well as the lectin are structural determinants of the lattice. The results are discussed in terms of multidimensional carbohydrate-lectin cross-linked complexes, as well as the signal transduction properties of multivalent lectins.

Binding Sites↗

PubMed2005

Regional accents: a rationale for intervening and competencies required.

Over the past 20 years, an increasing number of speech-language pathologists have stepped into the traditional arena of English as a Second Language to address the communication needs of accented individuals. Even with the growing support of ASHA, this continues to foster opposition from fellow professionals who feel that accent intervention falls outside the scope of our practice. This controversy steps up significantly when the accents in question are not foreign, but regional. This article presents a rationale for regional accent improvement training for the adult client, positions the unique demands of regional accents within the global terminology of accent, outlines the prerequisites for trainers, reviews the basics of a valid accent assessment, and addresses some preliminary instructional issues. This author suggests that trainers look outside the field of speech pathology for relevant research. Additionally, practical applications for working professionals require a clearer understanding of the American workplace and the field of human resources (management development).

Adult↗

PubMed2004

Highly specific and accurate selection of siRNAs for high-throughput functional assays.

MOTIVATION: Small interfering RNA (siRNA) is widely used in functional genomics to silence genes by decreasing their expression to study the resulting phenotypes. The possibility of performing large-scale functional assays by gene silencing accentuates the necessity of a software capable of the high-throughput design of highly specific siRNA. The main objective sought was the design of a large number of siRNAs with appropriate thermodynamic properties and, especially, high specificity. Since all the available procedures require, to some extent, manual processing of the results to guarantee specific results, specificity constitutes to date, the major obstacle to the complete automation of all the steps necessary for the selection of optimal candidate siRNAs. RESULT: Here, we present a program that for the first time completely automates the search for siRNAs. In SiDE, the most complete set of rules for the selection of siRNA candidates (including G+C content, nucleotides at determined positions, thermodynamic properties, propensity to form internal hairpins, etc.) is implemented and moreover, specificity is achieved by a conceptually new method. After selecting possible siRNA candidates with the optimal functional properties, putative unspecific matches, which can cause cross-hybridization, are checked in databases containing a unique entry for each gene. These truly non-redundant databases are constructed from the genome annotations (Ensembl). Also intron/exon boundaries, presence of polymorphisms (single nucleotide polymorphisms) specificity for either gene or transcript, and other features can be selected to be considered in the design of siRNAs. AVAILABILITY: The program is available as a web server at http://side.bioinfo.cnio.es. The program was written under the GPL license. CONTACT: jdopazo@cnio.es.

Algorithms↗

PubMed2004

ACMES: fast multiple-genome searches for short repeat sequences with concurrent cross-species information retrieval.

We have developed a web server for the life sciences community to use to search for short repeats of DNA sequence of length between 3 and 10,000 bases within multiple species. This search employs a unique and fast hash function approach. Our system also applies information retrieval algorithms to discover knowledge of cross-species conservation of repeat sequences. Furthermore, we have incorporated a part of the Gene Ontology database into our information retrieval algorithms to broaden the coverage of the search. Our web server and tutorial can be found at http://acmes.rnet.missouri.edu.

Algorithms↗

PubMed2005

Edwards FloTrac sensor and Vigileo monitor: easy, accurate, reliable cardiac output assessment using the arterial pulse wave.

Edwards Lifesciences has recently introduced the FloTrac sensor and Vigileo monitor system for monitoring cardiac output continuously. It does not require thermodilution or dye dilution, but rather bases its calculations on arterial waveform characteristics in conjunction with patient demographic data. It is unique among arterial waveform cardiac output systems in that it does not require calibration with another method. Studies thus far indicate that it is robust and accurate over a wide range of cardiac output and clinical conditions. It will be valuable in the care of many patients, such as those with critical illness, cardiovascular dysfunction, trauma or undergoing major surgery.

Algorithms↗

PubMed2002

Identification of the bovine gamma-aminobutyric acid type A receptor alpha subunit residues photolabeled by the imidazobenzodiazepine [3H]Ro15-4513.

Ligands binding to the benzodiazepine-binding site in gamma-aminobutyric acid type A (GABA(A)) receptors may allosterically modulate function. Depending upon the ligand, the coupling can either be positive (flunitrazepam), negative (Ro15-4513), or neutral (flumazenil). Specific amino acid determinants of benzodiazepine binding affinity and/or allosteric coupling have been identified within GABA(A) receptor alpha and gamma subunits that localize the binding site at the subunit interface. Previous photolabeling studies with [(3)H]flunitrazepam identified a primary site of incorporation at alpha(1)His-102, whereas studies with [(3)H]Ro15-4513 suggested incorporation into the alpha(1) subunit at unidentified amino acids C-terminal to alpha(1)His-102. To determine the site(s) of photoincorporation by Ro15-4513, we affinity-purified ( approximately 200-fold) GABA(A) receptor from detergent extracts of bovine cortex, photolabeled it with [(3)H]Ro15-4513, and identified (3)H-labeled amino acids by N-terminal sequence analysis of subunit fragments generated by sequential digestions with a panel of proteases. The patterns of (3)H release seen after each digestion of the labeled fragments determined the number of amino acids between the cleavage site and labeled residue, and the use of sequential proteolytic fragmentation identified patterns of cleavage sites unique to the different alpha subunits. Based upon this radiochemical sequence analysis, [(3)H]Ro15-4513 was found to selectively label the homologous tyrosines alpha(1)Tyr-210, alpha(2)Tyr-209, and alpha(3)Tyr-234, in GABA(A) receptors containing those subunits. These results are discussed in terms of a homology model of the benzodiazepine-binding site based on the molluscan acetylcholine-binding protein structure.

Affinity Labels↗

PubMed1986

A clinical and radiographic analysis of loosening of total knee arthroplasty components using a bilateral model.

Patients undergoing bilateral, simultaneous total knee replacement provide a unique opportunity to study the role of operative techniques in the development of radiolucent lines because variables such as age, sex, weight, diagnosis, and bone quality are internally matched when the result on one side is compared with that of the other. This allows more conclusive examination of operative factors, such as component alignment, level of tibial bone resection, and cement handling. With this as the objective, the clinical and radiographic results of the first 50 bilateral total knee replacements performed by the senior author were studied. Postoperative alignment was found to influence significantly the incidence of tibial radiolucent lines. Use of cement to reconstruct defects in the proximal tibia resulting from preoperative deformity consistently led to the development of radiolucent lines in the area of the defect. There was also indirect evidence that failure to achieve an intimate microinterlock at the bone-cement interface may play a major role in the development of tibial radiolucent lines.

Adult↗

PubMed2002

Transposable dual reporters for studying the structure-function relationships in membrane proteins: permissive sites in R. prowazekii ATP/ADP translocase.

A new approach to studying membrane topology and permissive sites in membrane proteins expressed in Escherichia coli is described. The method is based on in vitro transposition of mini-Tn5 derivatives bearing dual pho-lac reporters [Alexeyev, M. F., and Winkler, H. H. (1999) J. Mol. Biol. 285, 1503-1513]. Two mini-Tn5 transposons, Tnpholac1 and Tnpholac2, were designed in such a way that their insertions can be converted either by restriction-ligation or by in vivo Cre-lox recombination into either sandwich reporter fusions or short amino acid (aa) tags (25 or 42 aa long). A set of 48 unique insertions in the gene coding for the Rickettsia prowazekii ATP/ADP translocase (Tlc) was generated using Tnpholac2. The topological information generated by these insertions was found in to be in good agreement with the existing topological model. Subsequently, these insertions were converted into both 25 and 42 aa tags, and the activity of the resulting mutants was determined. Also, site-directed mutagenesis was used to construct insertions in the loops, where no transposon hops were discovered. Of 13 extramembrane domains in Tlc, only 3 (loops 7, 10, and 13) were found to be permissive, which is in marked contrast to previous observations in the E. coli lactose permease (LacY), where most insertions in extramembrane domains were demonstrated to be permissive. The permissiveness of the insertion after I368 in TM IX lead us to reconsider the boundaries for this TM by placing I368 on the interface between TM IX and loop 10. Interestingly, the 25 aa insertions consistently have 2-fold higher activity than the corresponding 42 aa insertions, which is also in contrast with observations made on LacY. Finally, in this study we report, for the first time, the frequency of 10 base pair target duplications generated by in vitro Tn5 transposition.

Amino Acid Sequence↗

PubMed2004

The origin of hematopoietic cell type diversity.

The hematopoietic system remains robust with regards to extrinsic perturbations, in sharp contrast with the stochastic behavior of hematopoeitic stem cells (HSCs) at the single cell level, suggesting that stability may be achieved within a stem cell system that undergoes constant self-renewal, commitment to differentiation and generates cell type diversification. Converging evidence at the interface of cellular, molecular and numerical studies suggests that diversity is generated by the chaotic dynamics of transcription factor networks within a cell and of the combination of growth factors and cytokines in the environment, both involving cooperation and competition. Current evidence indicates that HSCs are primed for multilineage gene expression. A subtle shift in transcription factor dosage is sufficient to perturb this equilibrium and to drive lineage commitment that involves a resolution of complexity at the molecular level and a transition towards less chaotic behavior. This dynamical instability establishes a state of responsiveness to extrinsic signals. Evolutionary conserved environmental cues that drive pattern formation or migratory behavior during embryonic development operate in the adult to influence the decision between self-renewal and differentiation in HSCs, as exemplified by the role of Notch1, Wnt proteins, BMPs and VEGF. In contrast, a network of cytokines uniquely present in mammalians influences later developmental stages, from progenitors with more restricted potentials (tri-, bi- or unipotent) to mature functional cells. These cytokines have co-opted the ancient Jak-STAT pathway but also appear to trigger lineage-affiliated transcription factors, thus linking environmental signaling to cell fate decisions.

Acute Disease↗

PubMed2004

A systematic method for identifying small-molecule modulators of protein-protein interactions.

Discovering small-molecule modulators of protein-protein interactions is a challenging task because of both the generally noncontiguous, large protein surfaces that form these interfaces and the shortage of high-throughput approaches capable of identifying such rare inhibitors. We describe here a robust and flexible methodology that couples disruption of protein-protein complexes to host cell survival. The feasibility of this approach was demonstrated through monitoring a small-molecule-mediated protein-protein association (FKBP12-rapamycin-FRAP) and two cases of dissociation (homodimeric HIV-1 protease and heterodimeric ribonucleotide reductase). For ribonucleotide reductase, we identified cyclic peptide inhibitors from genetically encoded libraries that dissociated the enzyme subunits. A solid-phase synthetic strategy and peptide ELISAs were developed to characterize these inhibitors, resulting in the discovery of cyclic peptides that operate in an unprecedented manner, thus highlighting the strengths of a functional approach. The ability of this method to process large libraries, coupled with the benefits of a genetic selection, allowed us to identify rare, uniquely active small-molecule modulators of protein-protein interactions at a frequency of less than one in 10 million.

Carrier Proteins↗

PubMed2002

HealthCyberMap: a semantic visual browser of medical Internet resources based on clinical codes and the human body metaphor.

OBJECTIVES: HealthCyberMap (HCM-http://healthcybermap.semanticweb.org) is a web-based service for healthcare professionals and librarians, patients and the public in general that aims at mapping parts of the health information resources in cyberspace in novel ways to improve their retrieval and navigation. METHODS AND SERVICE DESCRIPTION: HCM adopts a clinical metadata framework built upon a clinical coding ontology for the semantic indexing, classification and browsing of Internet health information resources. A resource metadata base holds information about selected resources. HCM then uses GIS (Geographic Information Systems) spatialization methods to generate interactive navigational cybermaps from the metadata base. These visual cybermaps are based on familiar medical metaphors. CONCLUSIONS: HCM cybermaps can be considered as semantically spatialized, ontology-based browsing views of the underlying resource metadata base. Using a clinical coding scheme as a metric for spatialization ('semantic distance') is unique to HCM and is very much suited for the semantic categorization and navigation of Internet health information resources. Clinical codes ensure reliable and unambiguous topical indexing of these resources. HCM also introduces a useful form of cyberspatial analysis for the detection of topical coverage gaps in the resource metadata base using choropleth (shaded) maps of human body systems.

Abstracting and Indexing↗

PubMed2002

Calculability analysis in underdetermined metabolic networks illustrated by a model of the central metabolism in purple nonsulfur bacteria.

Metabolite balancing has turned out to be a powerful computational tool in metabolic engineering. However, the linear equation systems occurring in this analysis are often underdetermined. If it is difficult or impossible to find the missing constraints, it is nevertheless feasible in some cases to determine the values of a subset of the unknown rates. Here, a procedure for finding out which reaction rates can be uniquely calculated in underdetermined metabolic networks and computing these rates is given. The method is based on the null space to the stoichiometry matrix corresponding to the reactions with unknown rates. It is shown that this method is considerably easier to handle than an algorithm given previously (Van der Heijden et al., 1994a). Furthermore, a useful elementary representation of the null space is presented which is closely related with the elementary flux modes. This unique representation is central to a more general approach to observability/calculability analysis. In particular, it allows one to find, in an easy way, those sets of measurable rates that enable a calculation of a certain unknown rate. Besides, rates which are never calculable by metabolite balancing may be easily detected by this method. The applicability of these methods is illustrated by a model of the central metabolism in purple nonsulfur bacteria. The photoheterotrophic growth of these representatives of anoxygenic photosynthetic bacteria is stoichiometrically analyzed. Interesting metabolic constraints caused by the necessary balancing of NADPH can be detected in a highly underdetermined system. This is, to our knowledge, the first application of stoichiometric analysis to the metabolic network in this bacteria group using metabolite balancing techniques. A new software tool, the FluxAnalyzer, is introduced. It allows quantitative and structural analysis of metabolic networks in a graphical user interface.

Algorithms↗

PubMed1993

The Atlanta FICSIT study: two exercise interventions to reduce frailty in elders.

This study examines the effect of two different exercise approaches on balance and frailty measures among more than 200 community-dwelling individuals greater than 70 years of age. Exercises are provided for 15 weekly sessions on an individual basis for participants randomly assigned to a Balance Training group. Training consists of center-of-mass feedback displayed on a motor under static conditions, or, in later sessions, as the floor surface is moved, with eyes open or closed. This high technology interface provides instantaneous information about displacement of body weight in space so that balance can be enhanced. An alternative procedure is comparatively simple and requires little expense or space. Tai Chi Quan was originally developed as a martial arts form but has been used for centuries in China as an exercise among elderly citizens. Participants randomly assigned to this intervention meet twice weekly for 15 weeks to learn a condensation of 108 Tai Chi forms into 10 that emphasize movement components often restricted or absent with aging. A third group serves as a control for exercise interventions by meeting weekly for 15 sessions to discuss topics of interest such as memory loss, drug management, and nutrition. All subjects are screened prior to assignment, and a host of physical, behavioral, and functional measures are assessed before and after the intervention as well as 4 months later. Measurements unique to the Atlanta site include: balance with eyes closed, programmed force-distribution changes when stance is perturbed, cardiovascular assessments, WAIS, Affects Balance Scale, and a survey of home environment.

Aged↗

PubMed1977

Functional organization of catfish retina.

1. The basic organization of the biphasic (or concentric) receptive field is established in the bipolar cells as the result of an interaction between two signals, one local representing the activity of a small number of receptors, and the other integrating (19, 20) or global (28) coming from the S space or a lamina formed by the horizontal cells (8, 14, 22, 29). 2. Bipolar-ganglion cell pairs are segregated into two types; A (on center) and B (off center) pairs. A depolarization of a bipolar cell produces spike discharges from ganglion cells of the same type and a hyperpolarization depresses their discharges. I haven't detected any cross talk between the types A and B pairs. Bipolar and ganglion cells must be interfaced by the classical chemical synapses, the only such kind in the catfish retina. 3. Horizontal and type N neurons form two lateral transmission systems, one distal and the other proximal (19, 20). Signals in the lateral systems are shared by the two receptive-field types and are not excitatory or inhibitory in themselves; it is incumbent upon the postsynaptic neurons to decide the polarity of the synaptic transmission. The horizontal cell participates directly in the formation of biphasic receptive fields of bipolar cells by providing their surrounding, whereas type N neuron seems to modify the receptive-field organization established in the bipolar cells. 4. Type N neurons are amacrine cells because they do not produce spike discharges (2, 18, 21) and because they influence the activity of both A and B receptive fields. 5. The function of the type C neuron is as unique as its structure (21) and is not fully clear as yet. It is not a conventional amacrine cell as the type N appears to be, nor is it a classical ganglion cell which forms either a type A or B receptive field (2). 6. Type Y neurons are a class of ganglion cells which forms either a type A or B receptive field.

Animals↗

PubMed2001

Claudin-1 is not restricted to tight junctions in the rat epididymis.

The blood-epididymal barrier creates a unique microenvironment critical for sperm maturation. There is little information on proteins comprising epididymal tight and adhering junctions or on factors regulating their expression. Claudins are a family of transmembrane proteins reported to be exclusively localized to tight junctions. In the present study the expression of claudin-l (Cl-1) was examined with respect to the different cell types of the epididymis and its various regions as well as its expression during postnatal development and regulation by testicular factors, using both immunocytochemistry and Northern blot analysis. RT-PCR of adult epididymal and testicular RNA (positive control) indicated that Cl-1 messenger RNA (mRNA) transcripts were present in all regions of the epididymis. In the adult, Cl-1 was localized immunocytochemically along the entire length of the lateral plasma membranes between adjacent principal cells, including apical areas containing tight junctions, as well as at the interface between principal and basal cells and along the basal plasma membrane of the epithelium in relation to the basement membrane. Northern blot analysis of adult epididymis with a rat Cl-1 complementary DNA indicated the presence of two hybridizing bands of 4.0 and 1.5 kb. Postnatally, in the caput-corpus and cauda epididymidis, mRNA levels for both transcripts were lowest on day 7. In the caput-corpus epididymidis, mRNA levels for the 1.5-kb transcript increased significantly between 7 and 14 days, whereas the levels of the 4.0-kb transcript were significantly higher by day 21. Postnatal studies revealed that in the initial segment and caput epididymidis, Cl-1 immunostaining was present along the entire length of the lateral plasma membranes of undifferentiated epididymal epithelial cells as early as day 7, including apical areas containing tight junctions. By day 21, staining was identical to that of adult animals, but as this is an age when androgen levels are not at their peak, the data would suggest that they are not a prominent factor regulating Cl-1 expression. Orchidectomy and orchidectomy plus testosterone replacement experiments revealed differences in Cl-1 immunostaining in the initial segment, suggesting that localization of Cl-1 in epididymal tight junctions is androgen dependant. Thus, Cl-1 expression in the initial segment appears to be only partially under the control of androgens. However, in all other epididymal regions, orchidectomy with or without testosterone replacement, revealed no changes to the normal staining pattern, suggesting that androgens do not regulate Cl-1 expression in these regions. Taken together, these studies demonstrate that Cl-1 expression in the epididymis is not localized exclusively to tight junctions, but appears along the entire interfaces of adjacent epithelial cells as well as along the basal plasma membrane, suggesting a role for Cl-1 as an adhesion molecule. The data also suggest that the regulation of Cl-1 in the epididymis is complex and multifactorial.

Aging↗

PubMedDate not supplied

The Health Commons and care of New Mexico's uninsured.

PURPOSE: A seamless system of social, behavioral, and medical services for the uninsured was created to address the social determinants of disease, reduce health disparities, and foster local economic development in 2 inner-city neighborhoods and 2 rural counties in New Mexico. METHODS: Our family medicine department helped urban and rural communities that had large uninsured, minority populations create Health Commons models. These models of care are characterized by health planning shared by community stakeholders; 1-stop shopping for medical, behavioral, and social services; employment of community health workers bridging the clinic and the community; and job creation. RESULTS: Outcomes of the Health Commons included creation of a Web-based assignment of uninsured emergency department patients to primary care homes, reducing return visits by 31%; creation of a Web-based interface allowing partner organizations with incompatible information systems to share medical information; and creation of a statewide telephone Health Advice Line offering rural and urban uninsured individuals access to health and social service information and referrals 24 hours a day, 7 days a week. The Health Commons created jobs and has been sustained by attracting local investment and external public and private funding for its products. Our department's role in developing the Health Commons helped the academic health center (AHC) form mutually beneficial community partnerships with surrounding and distant urban and rural communities. CONCLUSIONS: Broad stakeholder participation built trust and investment in the Health Commons, expanding services for the uninsured. This participation also fostered marketable innovations applicable to all Health Commons' sites. Family medicine can promote the Health Commons as a venue for linking complementary strengths of the AHC and the community, while addressing the unique needs of each. Overall, our experience suggests that family medicine can play a leadership role in building collaborative approaches to seemingly intractable health problems among the uninsured, benefiting not only the community, but also the AHC.

Community Health Centers↗

PubMed1994

Dynamic expression patterns of tenascin, proteoglycans, and cell adhesion molecules during human hair follicle morphogenesis.

The development of skin appendages such as hair, feathers, and teeth is brought about by reciprocal interactions between epidermal and mesenchymal tissues and is thought to be influenced in part by cell adhesion molecules and components of the extracellular matrix. The developmental distributions of tenascin, neural cell adhesion molecule (NCAM), E-cadherin, intercellular adhesion molecule 1 (ICAM-1), chondroitin sulfate proteoglycan (CSPG), and the heparan sulfate proteoglycan perlecan were studied in relation to hair follicle morphogenesis in fetal human skin. Tenascin first appeared in developing skin in focal concentrations at the epidermal-mesenchymal interface, just prior to, and presumably correlated with, hair follicle initiation. Tenascin immunostaining remained prominent in the basement membrane zone and extracellular matrix of the follicle sheath during subsequent morphogenetic stages. Two forms of tenascin (M(r) 250 x 10(3) and 280-300 x 10(3)), were revealed by Western blots of skin extracts. NCAM immunolabeling was initially present throughout the dermis, and became progressively restricted to the dermal condensation and the follicle sheath. Western blot analysis revealed an isoform of NCAM (M(r) 160 x 10(3)) which lacked polysialic acid. At all stages, E-cadherin staining was diminished on follicle cells situated adjacent to the basement membrane, relative to cells in the follicle interior. Follicle-specific immunostaining for ICAM-1 was transient, appearing only at the pre-germ and hair germ stages of development. Antibodies to three distinct CSPG determinants revealed unique immunolabeling patterns following follicle initiation: One CSPG epitope co-distributed with tenascin in the follicle basement membrane and follicle sheath extracellular matrix; one CSPG epitope was similarly expressed, and was also found on follicle epithelial cells; and the third CSPG determinant was noticeably absent from the follicle sheath during elongation of the developing appendage. Perlecan was concentrated in the dermal papilla, in addition to its distribution in all skin basement membranes. A model for how these diverse molecules may interact to influence human hair follicle morphogenesis is presented.

Blotting, Western↗