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A case of bow hunter's stroke caused by non-dominant vertebral artery.

Rotational movements in the territory of vertebrobasilar artery of the head and neck can induce vertebrobasilar insufficiency (VBI) or infarction. The term "bow hunter's stroke" or "rotational VBI" has been used to describe this clinical syndrome. In most cases, symptoms were provoked because of involvement of a dominant vertebral artery (VA) with hypoplasia or occlusion of the contralateral VA. The author presented a case in which bow hunter's stroke was caused by occlusion of a non-dominant VA ending in the posterior inferior cerebellar artery (PICA). Diagnosis of rotational VBI was based on stereotypical clinical symptoms related to head rotation and hemodynamic study of the effects of head rotation. VA compression was documented in dynamic ultrasonography including the disappearance of end-diastolic flow in extracranial portion of VA and marked reduction in blood flow velocity (more than 50%) in the intracranial portion of VA upon head rotation. We emphasize that rotational occlusion of this anatomical variation is an important cause of VBI. This may cause permanent neurological deficits if left undiagnosed.

Aged↗

Association between genetic variation of CACNA1H and childhood absence epilepsy.

Direct sequencing of exons 3 to 35 and the exon-intron boundaries of the CACNA1H gene was conducted in 118 childhood absence epilepsy patients of Han ethnicity recruited from North China. Sixty-eight variations have been detected in the CACNA1H gene, and, among the variations identified, 12 were missense mutations and only found in 14 of the 118 patients in a heterozygous state, but not in any of 230 unrelated controls. The identified missense mutations occurred in the highly conserved residues of the T-type calcium channel gene. Our results suggest that CACNA1H might be an important susceptibility gene involved in the pathogenesis of childhood absence epilepsy.

Age of Onset↗

Recombination and clonal groupings within Helicobacter pylori from different geographical regions.

A collection of 20 strains of Helicobacter pylori from several regions of the world was studied to better understand the population genetic structure and diversity of this species. Sequences of fragments from seven housekeeping genes (atpA, efp, mutY, ppa, trpC, ureI, yphC ) and two virulence-associated genes (cagA, vacA) showed high levels of synonymous sequence variation (mean percentage Ks of 10-27%) and lower levels of non-synonymous variation (mean percentage Ka of 0.2-5.6%). Cluster analysis of pairwise differences between alleles revealed the existence of two weakly clonal groupings, which included half of the strains investigated. All six strains isolated from Japanese and coastal Chinese were assigned to the 'Asian' clonal grouping, probably reflecting descent from a distinct common ancestor. The clonal groupings were not totally uniform; recombination, as measured by the homoplasy test and compatibility matrices, was extremely common within all genes tested, except cagA. The fact that clonal descent could still be discerned despite such frequent recombination possibly reflects founder effects and geographical separation and/or selection for particular alleles of these genes.

Aldose-Ketose Isomerases↗

Evolutionary processes in a continental island system: molecular phylogeography of the Aegean Nigella arvensis alliance (Ranunculaceae) inferred from chloroplast DNA.

Continental shelf island systems, created by rising sea levels, provide a premier setting for studying the effects of past fragmentation, dispersal, and genetic drift on taxon diversification. We used phylogeographical (nested clade) and population genetic analyses to elucidate the relative roles of these processes in the evolutionary history of the Aegean Nigella arvensis alliance (= 'coenospecies'). We surveyed chloroplast DNA (cpDNA) variation in 455 individuals from 47 populations (nine taxa) of the alliance throughout its core range in the Aegean Archipelago and surrounding mainland areas of Greece and Turkey. The study revealed the presence of three major lineages, with largely nonoverlapping distributions in the Western, Central, and Eastern Aegean. There is evidence supporting the idea that these major lineages evolved in situ from a widespread (pan-Aegean) ancestral stock as a result of multiple fragmentation events, possibly due to the influence of post-Messinian sea flooding, Pleistocene eustatic changes and corresponding climate fluctuations. Over-sea dispersal and founder events appear to have played a rather insignificant role in the group's history. Rather, all analytical approaches identified the alliance as an organism group with poor seed dispersal capabilities and a susceptibility to genetic drift. In particular, we inferred that the observed level of cpDNA differentiation between Kikladian island populations of Nigella degenii largely reflects population history, (viz. Holocene island fragmentation) and genetic drift in the near absence of seed flow since their time of common ancestry. Overall, our cpDNA data for the N. arvensis alliance in general, and N. degenii in particular, indicate that historical events were important in determining the phylogeographical patterns seen, and that genetic drift has historically been relatively more influential on population structure than has cytoplasmic gene flow.

Base Sequence↗

Variability of velocity and duration of microembolic signals detected by bigated transcranial Doppler sonography in carotid endarterectomy.

OBJECTIVE: To differentiate between gaseous and particular microemboli in carotid surgery one clinical approach is the interpretation of the effective sample volume length (SVL). We investigated whether such a clinical interpretation is based on reproducible measurements. METHODS: Microembolic signals (MES) recorded during carotid endarterectomy by a bigated transcranial Doppler device were analyzed off-line. In the two sample volumes, the duration and the velocity of the MES were measured by two observers independently from each other twice within 2 weeks. The SVL of the MES were calculated by multiplying duration with velocity. RESULTS: In the anatomical proximal sample volume 215 MES were recorded of which 203 (94.5%) were also present in the distal. The SVL medians of the MES were 2.2-4.1 mm lower in the distal than in the proximal sample volume as a result of lower velocity and shorter duration of the MES in the distal sample volume. The median of the paired differences of the SVL was 0.2 mm (interquartile range: 0.0-1.2) in the proximal sample volume and 0.8 mm (0.2-1.8) in the distal sample volume for observer 1, and 0.6 mm (0.4-2.2) and 0.9 mm (0.5-1.6) for observer 2. The median of the paired differences of the SVL between the observers was 1.4 mm (1.2-2.9) in the proximal sample volume and 1.6 mm (1.3-3.0) in the distal. CONCLUSION: The intra- and interobserver agreement on calculating SVL is good. However, the depth of insonation influences some features of embolic signals.

Aged↗

Identification and distribution of HIV type 1 genetic diversity and protease inhibitor resistance-associated mutations in Shanghai, P. R. China.

OBJECTIVE: To investigate the genetic diversity of the HIV-1 circulating in Shanghai and to analyze the mutations in the protease (PR) gene associated with resistance to protease inhibitors (PIs). DESIGN: The genetic diversity of HIV-1 and PI resistance-associated mutations was studied in 40 Shanghai HIV-1-seropositive treatment-naive residents. The patients studied were exposed to the infection mainly through contaminated blood products (hemophiliacs) (n = 17) and sexual contacts (n = 19). Samples from 2 injecting drug users (IDUs) and 2 children born to HIV-1 infected mothers were also analyzed. METHODS: HIV-1 partial gag, pol, and env genes in infected plasma samples were amplified by reverse transcriptase polymerase chain reaction, sequenced, and phylogenetically analyzed. Analysis of PI resistance-associated amino acid substitution in PR was performed. RESULTS: HIV-1 genes in 38 of the 40 plasma samples were successfully amplified and analyzed. Polymerase chain reaction amplification was successful for 16/17 hemophilia patients and 18/19 sexually infected individuals. While all the 16 hemophilia patients infected through contaminated blood products were infected with subtype B', the 18 patients infected through sexual contact were infected with several subtypes including subtype A (n = 2), B (n = 4), B' (n = 1), C (n = 2), CRF08_BC (n = 1), CRF01_AE (n = 7), and intersubtype recombinant CRF01_AE/B (n = 1). The 2 IDUs were infected with CRF08_BC and the 2 children born to HIV-1 infected mothers were infected with subtype B' and CRF01_AE. PI resistance-associated amino acid substitutions were found at 1 codon in primary and 7 codons in secondary regions of the PR gene. Amino acid substitutions were more frequently found in the B/B' sequences (69%) than in the non-B sequences (31%). Substitutions characteristic with the subtype B/B' sequences mainly among hemophiliacs included L63P (87%), A71V/T (27%), and V77I (93%) while those that characterized the non-B sequences mainly found among heterosexuals included M36I (69%) and K20R (19%). CONCLUSION: This study reveals the presence of multiple HIV-1 subtypes and recombinants infecting Shanghai residents. The broad HIV-1 diversity is being introduced into this city through heterosexual contacts. This study also reveals that viruses infecting these treatment-naive patients have acquired both primary or secondary mutations in their PR genes. These studies should provide the basis for further epidemiologic surveys of HIV-1 subtypes and set strategies for treatment intervention and vaccine programs.

Adolescent↗

Strain-level differences in Gardnerella urinary tract persistence and pathogenesis are consistent with comparative phylogenomic analyses.

BACKGROUND: Gardnerella is a genus of gram variable anaerobic bacteria that is commonly present in the female urogenital tract, especially during bacterial vaginosis (BV). BV is linked with increased risk of urinary tract infections (UTI) and Gardnerella has been frequently detected in urine collected directly from the bladder. Understanding the contribution of Gardnerella to urogenital pathogenesis has been complicated by its genetic heterogeneity and a shortage of data from in vivo models. Recently, a clinical isolate of Gardnerella displayed covert pathogenesis in a mouse urinary tract inoculation model, triggering urothelial exfoliation and promoting UTI by uropathogenic E. coli. Data from clinical studies suggests differential association of Gardnerella phylogenetic clades with BV or urogenital infections. In vitro data has demonstrated heterogeneity in the presence and expression of putative virulence determinants between Gardnerella strains. This study was designed to compare diverse Gardnerella strains in vivo to identify genomic variation associated with urinary tract persistence and pathogenesis. METHODS: Eighteen Gardnerella clinical isolates from each of the four main phylogenetic clades were individually inoculated transurethrally into female C57BL/6 mice. Bacteriuria was monitored by quantitative culturing of Gardnerella in urine. Pathologic features were assessed by immunofluorescent and histological staining of bladder tissues. Pan-genome phylogenetic analyses were performed on the 18 Gardnerella isolates used for mouse infections to identify accessory genes that were associated with observable in vivo phenotypes, including long and short-term persistence, urothelial exfoliation and bladder edema. Genes that were significantly associated to phenotype were then matched against a pangenome analysis of 291 publicly available Gardnerella genomes to determine the conservation of these putative colonization and virulence factors across the genus. RESULTS: Gardnerella strains displayed clear differences in persistence and pathogenesis in the mouse bladder that were congruent with phylogeny. Clade 2 strains were more persistent in the urinary tract whereas strains from the other three clades either caused transient bacteriuria or were undetectable. Strains from clade 2 and 4 induced urothelial exfoliation while edema was triggered by strains from clades 2, 3 and 4. Pangenome analyses revealed 45 genes that were associated with in vivo persistence and pathogenicity. Among the wider 291 publicly available genomes, clade 2 strains encoded more of the genes associated with bacteriuria phenotypes compared to strains in the other three clades. Exfoliation-associated genes were present in most clade 4 strains. Clade 3 strains lack most of the in vivo-associated genes, whereas clade 1 strains were more heterogenous. CONCLUSIONS: This study provides in vivo evidence for differential urinary tract colonization and pathogenesis by strains from different clades/species within the genus Gardnerella and identifies new putative persistence and virulence factors. Utilizing the in vivo data from tested strains, pangenome analyses predicts that clade 2 Gardnerella are the most likely to persist in the urinary tract and that clades 2 and 4 have the highest uropathogenic potential. These findings inform future targeted screening and treatment approaches aimed at limiting harmful Gardnerella urinary tract exposures.

Journal Article↗

Evidence for rapid selection and deletion of HIV-1 subpopulations in vivo by V3-specific neutralizing antibody: a model of humoral-associated selection.

Emergence in two chimpanzees of HIV-1 HTLV-IIIB variants resistant to neutralization by the pre-existing antibody is described. Viruses isolated from the HTLV-IIIB gp120 vaccinated and challenged animal were more resistant to neutralization, had more heterogenic genomes and showed more pronounced antigenic drift as determined by serotypic neutralization analysis than viruses isolated from the naive infected animal, indicating immune pressure as the selective mechanism. The earliest selecting antibody population detected in the chimpanzees appeared to be conformationally dependent. This was demonstrated by its ability to neutralize only the most replication-competent sub-populations of the HTLV-IIIB inoculum strain, yet was found to bind a HTLV-IIIB common nonapeptide (IQRGPGRAF) derived from the gp120 isolate-specific 3rd variable domain (V3) also known to induce isolate-specific neutralization in multiple species. Each of the recovered isolates had become resistant to neutralization by both a monoclonal (0.5 beta) and polyclonal HTLV-IIIB gp120 V3-specific antibody by as much as 16 to 256-fold. Amplification of the V3 coding sequence by polymerase chain reaction and subsequent sequence analysis of the neutralization-resistant variants obtained from in vivo infected animals indicated that resistance to neutralization was conferred by changes outside the direct binding site for the selective neutralizing antibody. Further studies indicated that apparent neutralization-resistant variants, yielded after in vitro passage through chimpanzee and human peripheral blood mononuclear cell cultures void of HIV-specific antibody, result from the homogenic amplification of the more replication competent sub-population pre-existing in the original viral stock. These faster replicating sub-populations appear to dominate initially and therefore are the initial prime targets recognized by the chimpanzee humoral immune system upon infection in vivo and thus eliminated. The described finding of virus escape due to a conformationally-induced flexibility of the major neutralization epitope termed "conformational-V3 hypervariability", coupled to the known primary amino acid hypervariability of this epitope (V3) termed "linear-V3 hypervariability", may be all that is required by the virus to survive in an otherwise effective humoral immune system.

Amino Acid Sequence↗

Permanent tooth calcification in chimpanzees (Pan troglodytes): patterns and polymorphisms.

Tooth calcification is an important developmental marker for use in constructing models for early hominid life history, particularly for its application to the fossil record. As chimpanzees are commonly utilized in interspecific comparisons in such research, this study aims to improve available baseline data for tooth calcification patterns in chimpanzees (Pan troglodytes), and to quantify basic patterns and polymorphisms. We present an analysis of developmental patterns for the left mandibular dentition (I1-M3) based on intraoral radiographs obtained from a cross-sectional sample of chimpanzees (58 males, 60 females) housed at LEMSIP (NYU Medical Center) and Yerkes (Emory University). No significant differences with previous descriptions of the basic sequences of tooth calcification in chimpanzees were found, but variation in such patterns was documented for the first time. In the overall sequence, polymorphisms between the canine and the group (M2 P4 P3) reached significant levels. This is due to the relative delay in canine crown formation compared to other teeth. Differences in the basic sequence between males and females were recorded, but are due to minor shifts in the percentages of occurrence for polymorphic sequences which are common to both genders. Perhaps our most important findings are that a) different polymorphic sequences occur in tooth calcification and tooth emergence in chimpanzees, and b) developmental relationships among teeth fluctuate throughout tooth calcification. Thus, characterizations of dental developmental patterns based on particular stages of development cannot necessarily be extrapolated to other stages without supporting data.

Animals↗

Metaproteomic Analysis to Assess the Impact of Storage Media on Human Gut Microbiome in Fecal Samples.

The human gut microbiome is a diverse community of microorganisms residing in the gastrointestinal tract. The storage condition of fecal samples may impact the taxonomic and protein compositions of microbiomes in these samples. Here, we performed a mass spectrometry-based metaproteomic study to assess the impact of storage media on human gut microbiome in fecal samples. We evaluated FDA-authorized OMNIgene·GUT (OG), phosphate-buffered saline (PBS), and RNALater (RNAL) buffers and identified 38,185 microbial peptides corresponding to 7348 microbial proteins, which matched 16 phyla, 20 classes, 50 orders, 104 families, 332 genera, and 453 species. We found a high similarity among the fecal microbiomes preserved in OG, PBS, and RNAL in terms of the identification of proteins, taxa, and functional annotations. Both alpha and beta diversity suggested the high similarity among samples stored in the three media. Nonetheless, we also found some notable differences among buffers regarding the abundances of a few taxon groups. A partial human proteome (over 400 proteins) was identified in the fecal samples, with most of these proteins associated with the membrane and extracellular regions. The findings indicate the similarity among microbiomes in the fecal samples stored in OG, PBS, and RNAL regarding proteome profile, taxa, and functional capacity. SUMMARY: This study thoroughly analyzed and compared the metaproteomes of fecal samples preserved at -80°C in PBS, RNALater, and OMNIgene·GUT Dx buffers, offering novel insights into the effectiveness of these buffers in maintaining the stability and composition of the human gut microbiome. We found a high similarity in the identification and quantification of proteins, taxa, and functional annotations across the three buffers, with notable quantitative differences highlighting subtle yet important variations in preservation efficacy. The unique datasets and findings could offer valuable revelations into the impact of fecal sample preservation on translational and clinical analyses of the human gut microbiome.

Humans↗

Audit of a multidisciplinary approach to the care of children with unilateral and bilateral cleft lip and palate.

Cleft lip and palate affects the child in many ways, particularly appearance, dental arch relationships, growth of the face, and speech development. The key to successful care is management in a multidisciplinary team adhering to a well-designed protocol, and careful audit of results. We present the intermediate outcome audit of 15 patients with complete bilateral and unilateral cleft lip and palate whose condition was managed in a multidisciplinary team according to a strict protocol. We give the results observations of operations of a single surgeon's functional primary surgery over a 6-year period in terms of dental arch relationships, cephalometric analyses, aesthetic assessments, and speech analysis. The results show good early facial growth, with dental arch relationships appropriate for the age and group; we found only minor speech discrepancies, with no patients requiring pharyngoplasty. The results show the importance of multidisciplinary management, the value of keeping to sound surgical protocols, and functional techniques in cleft lip and palate surgery. Our study includes the neglected group of children who have bilateral cleft lip and palate, and it conforms to the style of pan-European projects.

Cephalometry↗

Gene trees and hominoid phylogeny.

Here we present a DNA sequence study that incorporates intraspecific variation from all five genera of hominoids (apes and humans). Recently it has been claimed that using single individuals to analyze species' relationships might be misleading if within-species variation is great. Our results indicate that despite high intraspecific variation in mitochondrial cytochrome oxidase subunit II gene sequences of some hominoids, humans and chimpanzees are nonetheless significantly most closely related. We also report the observation that variation within the gorilla species exceeds that between common and pygmy chimpanzee species, a finding with implications for conservation. In contrast, humans are less mitochondrially diverse than lowland gorillas inhabiting western Africa.

Animals↗

New cytochrome P450 2D6*56 allele identified by genotype/phenotype analysis of cryopreserved human hepatocytes.

Genotype/phenotype analysis with human hepatocytes has identified a new inactive CYP2D6 allele, CYP2D6*56. Cryopreserved human hepatocytes from 51 livers were evaluated for CYP2D6 activity with dextromethorphan as the probe substrate. Hepatocyte lots that lacked CYP2D6 activity were further evaluated for CYP2D6 expression and known genetic variations, including CYP2D6*2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *14, *15, *17, *18, *19, *20, *25, *26, *29, *30, *35, *40, *41, *43, and various multiple copy CYP2D6 alleles (*1xn, *2xn, and *4xn) by the AmpliChip CYP450 prototype microarray (Roche Molecular Systems, Inc., Branchburg, NJ). Two discrepancies were uncovered between the CYP2D6 genotype and activity by this approach. In one sample, a previously unreported 3201C 224 T transition in exon 7 resulted in Arg344(CGA) being replaced by a stop codon (TGA), resulting in a CYP2D6 enzyme lacking the terminal 153 amino acids. This allele was given the designation of CYP2D6*56 and the GenBank accession number DQ282162. The lack of CYP2D6 activity in cryopreserved hepatocytes and microsomes found in the second sample, despite a normal level of CYP2D6 expression and a genotype (*10/*1) predictive of normal CYP2D6 activity, was attributed to enzyme inactivation by an unknown metabolite. The identification and characterization of the CYP2D6*56 allele indicates that commercial cryopreserved human hepatocytes may provide a valuable means to rapidly identify genetic variations with functional relevance. This integrated approach of identifying alleles and examining allele relationships to gene expression and function could be of tremendous value to understanding the mechanism responsible for functional differences in gene variation. The commercial availability of human cryopreserved hepatocytes also makes this potential readily available to any who are interested in it, not just those with access to private liver banks.

Alleles↗

Phylogeography and genetic ancestry of tigers (Panthera tigris).

Eight traditional subspecies of tiger (Panthera tigris),of which three recently became extinct, are commonly recognized on the basis of geographic isolation and morphological characteristics. To investigate the species' evolutionary history and to establish objective methods for subspecies recognition, voucher specimens of blood, skin, hair, and/or skin biopsies from 134 tigers with verified geographic origins or heritage across the whole distribution range were examined for three molecular markers: (1) 4.0 kb of mitochondrial DNA (mtDNA) sequence; (2) allele variation in the nuclear major histocompatibility complex class II DRB gene; and (3) composite nuclear microsatellite genotypes based on 30 loci. Relatively low genetic variation with mtDNA,DRB,and microsatellite loci was found, but significant population subdivision was nonetheless apparent among five living subspecies. In addition, a distinct partition of the Indochinese subspecies P. t. corbetti in to northern Indochinese and Malayan Peninsula populations was discovered. Population genetic structure would suggest recognition of six taxonomic units or subspecies: (1) Amur tiger P. t. altaica; (2) northern Indochinese tiger P. t. corbetti; (3) South China tiger P. t. amoyensis; (4) Malayan tiger P. t. jacksoni, named for the tiger conservationist Peter Jackson; (5) Sumatran tiger P. t. sumatrae; and (6) Bengal tiger P. t. tigris. The proposed South China tiger lineage is tentative due to limited sampling. The age of the most recent common ancestor for tiger mtDNA was estimated to be 72,000-108,000 y, relatively younger than some other Panthera species. A combination of population expansions, reduced gene flow, and genetic drift following the last genetic diminution, and the recent anthropogenic range contraction, have led to the distinct genetic partitions. These results provide an explicit basis for subspecies recognition and will lead to the improved management and conservation of these recently isolated but distinct geographic populations of tigers.

Alleles↗

Bovine interleukin 2 (IL-2) production and activity on bovine and murine cell lines.

Long-term growth of T cell cultures requires addition of Interleukin 2 (IL-2). In order to maintain bovine cultures, optimal conditions for bovine IL-2 production were defined using peripheral blood mononuclear cells (PBM). Irradiation and preculture enhanced IL-2 production possibly by reducing suppressor activity. IL-2 activity was also detected in Bovine Herpesvirus Type 1-stimulated cultures. Unlike mitogen-stimulated cultures, a wide variation in IL-2 activity was seen between supernatants produced by virus-stimulated cells from different animals indicating the clonal nature of antigen specific cells from individuals. Bovine IL-2-dependent cells used to quantitate IL-2 activity were characterized as: PNA, esterase negative, H4+ (anti Ia-like), B29+ (anti-pan T cell), and C5- (anti-monocyte). The observations that bovine IL-2 can maintain activated murine cells, CTLL-20 and HT-2, could lead to the replacement of rat IL-2 with bovine IL-2 in long-term murine cultures. Conditions described here result in large volumes of active medium.

Animals↗

Long-term effects of hysterectomy and bilateral oophorectomy on lymphoid tissue in female Lewis rats.

The effects of ovariectomy, ovariohysterectomy and hysterectomy on morphologically demonstrable characteristics of lymphoid organs, peripheral white blood cell counts and antibody production against sheep red blood cells (SRBC) were studied in female Lewis rats. Removal of ovaries induced enlarged thymus weight and cellularity. No differences were observed between the groups in spleen weight, while hysterectomy together with ovariectomy influenced relative uterus draining lymph node (UDLN) weight. The percent numbers of pan T, helper T lymphocytes, cytotoxic/suppressor T cells and IgG bearing cells (B lymphocytes) of all investigated organs showed only moderate changes caused by the surgical procedures. In contrast, removal of ovaries generated elevated total leukocyte and lymphocyte counts in peripheral blood. The changes in absolute blood lymphocyte counts were accompanied by similar variations in absolute T and B lymphocyte numbers. Ovariohysterectomy had slightly greater effects on these parameters than ovariectomy alone. In addition, ovaries and uterus had only moderate influences on systemic immune responses toward SRBC. In conclusion, the present results indicate that the removal of ovaries and uterus can modify morphological characteristics of lymphoid organs and peripheral blood but antibody production showed only moderate changes caused by the surgical procedures.

Animals↗

The epidermal nerve fibre network: characterization of nerve fibres in human skin by confocal microscopy and assessment of racial variations.

As a first line of defence, the skin is equipped with a complex and interactive nerve fibre system to detect irritants and maintain homeostasis. The dermal component of this fibre network has been well characterized and fibres are known to extend throughout the viable epidermis as free nerve endings. To date, this epidermal component remains poorly characterized. We have visualized human volar forearm epidermal nerve fibres by laser-scanning confocal microscopy using the pan-neuronal marker, protein gene-product 9.5 and specific antibodies to substance P. calcitonin gene-related peptide and nerve growth factor. In addition to the varicose free nerve endings, there is a 3-D fibre network in normal human epidermis, with frequent branching of fibres. Branching can be seen to converge on a central trunk apparently extending to the dermis. Thin unmyelinated fibres can be seen in all layers of the viable epidermis. Substance P staining is rarely observed and is much less intense than the protein gene-product 9.5 staining. Calcitonin gene-related peptide and nerve growth factor were not detected in volar forearm epidermis by this method. Pretreatment of the skin in vivo with the neuropharmacological agent, capsaicin, resulted in loss of epidermal fibre staining indicating that these are sensory fibres of the primary C-afferent type. Epidermal innervation in racial and ethnic skin types was also assessed. No apparent difference in innervation was observed between European caucasian and Japanese/Chinese skin at the architectural or biochemical level, i.e. the presence, properties and biochemical content of fibres was similar in all cases tested.

Asian People↗