The glycoprotein of the carcinoembryonic antigen (CEA) gene family expressed on epithelial keratinocytes in viral warts.
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Carcinoembryonic Antigen↗
Biomedical subjects
K Egawa
Publications and source records attributed to K Egawa.
Pigmented viral warts: a clinical and histopathological study including human papillomavirus typing.
Although clinical, histological and viral correlations have recently been established among pigmented warts, homogeneous intracytoplasmic inclusion bodies and related types of human papillomavirus (HPV) (HPV 65, 4 and 60), the causes of the pigmentation remain unknown. In this study, comparative histological and histochemical analyses were performed with 53 pigmented (34 HPV 65-induced, 12 HPV 4-induced and seven HPV 60-induced) and 73 non-pigmented warts (27 HPV 2-induced, 23 HPV 1-induced, 12 HPV 63-induced, six unknown HPV-type induced and five HPV 60 induced) to clarify the causes of the pigmentation. Electron microscopy was also used to examine the pigmented warts. Many melanin blockade melanocytes were identified in all of the pigmented warts with Masson-Fontana staining and electron microscopy, and increased melanin in keratinocytes was also noted in 22 pigmented warts, suggesting that the dispersion of melanin granules in the dendrites of the melanin blockade melanocytes and the increased melanin granules in keratinocytes are the primary contributors to the pigmentation of the warts. The homogeneous intracytoplasmic inclusion bodies might also play a part in the darkening of the warts, as only the cases which had the inclusion bodies as well as the melanin blockade melanocytes were clinically pigmented. Although melanin blockade melanocytes were seen in a few cases of HPV 1- and HPV 2-induced warts in which the homogeneous inclusion bodies were not observed, the warts were not clinically pigmented. Melanin blockade melanocytes were not seen in any of the HPV 63-induced non-pigmented warts. In conclusion, the pigmented warts were associated with one of the related types of HPV (HPV 65, 4 and 60), and the pigmentation of the lesions is thus thought to be caused primarily by melanin blockade melanocytes. The homogeneous intracytoplasmic inclusion bodies might also play a part in the darkening of the lesions. This is the first report dealing with the pigmentary disorder associated with specific types of HPV.
Adolescent↗
Human papillomavirus 57 identified in a plantar epidermoid cyst.
We report a 23-year-old Japanese man who had plantar warts on the right sole, beneath one of which an epidermoid cyst developed. On microscopic examination, an acanthotic epidermis markedly invaginated into the underlying dermis, resulting in an open epidermoid cyst. Not only the polymerase chain reaction but also an in situ hybridization detected HPV 57 DNA in the cyst. HPV 60 is the only type of HPV that has been identified in epidermoid cysts. To our knowledge, this is the first case report of an epidermoid cyst, in which a different type of virus from HPV 60 was identified. Histological features of the cyst were also different those of HPV 60-associated epidermoid cysts.
Adult↗
Immunohistochemical demonstration of carcinoembryonic antigen and related antigens in various cutaneous keratinous neoplasms and verruca vulgaris.
Carcinoembryonic antigen (CEA), which is a well-known marker for the normal sweat gland apparatus and its neoplasms in the skin, was recently demonstrated in sebaceous neoplasms. The aim of this study was to examine the expression of CEA and related antigens in the other cutaneous keratinous neoplasms and verruca vulgaris. Normal adult skin, squamous cell carcinoma (SCC), senile keratosis, Bowen's disease, basal cell carcinoma (BCC), seborrhoeic keratosis and verruca vulgaris were stained immunohistochemically with a panel of monoclonal and polyclonal antibodies that recognize different epitopes of CEA and related molecules. Localization of the antigens was compared with that of involucrin and proliferating cell nuclear antigen. The strongest expression of CEA-related antigens, other than non-specific cross-reacting antigen (NCA) -50/90, was seen in SCC and verruca vulgaris, while no detectable expression was seen in BCC. Senile keratosis, Bowen's disease and seborrhoeic keratosis showed the predominance of the CEA-related antigens over CEA weakly expressed. Strong expression of both CEA and NCA-50/90 was seen only in SCC. All the expressions were limited to the cells situated in the upper epidermal cell layers of the tumours, at the centre of tumour islands in SCC and along the pseudohorn cysts in seborrhoeic keratosis, where involucrin was coexpressed. We suggest that CEA and related antigens are not only markers for sweat gland differentiation in the skin, as currently accepted, but are also expressed in various cutaneous keratinous neoplasms and verruca vulgaris. The expression may correlate with the terminal differentiation of the tumour cells, the strong coexpression of CEA and NCA-50/90 may correlate with the malignant potential of the tumour types, and the mechanisms that control the expression of CEA and related antigens in the neoplasms may be similar to those operative in verruca vulgaris.
Adult↗
Human papillomaviruses are commonly found in normal skin of immunocompetent hosts.
We have previously demonstrated, by the combined application of two degenerate polymerase chain reaction primer sets, the presence of human papillomavirus (HPV) DNA in 91% of cutaneous squamous cell cancers from renal allograft recipients, with multiple types being present in one-third of these tumors. Five HPV types--HPV 20, HPV 23, HPV 38, DL40, and DL267--accounted for 73% of positive results. These HPV types are all related to the epidermodysplasia verruciformis group, and HPV 38 was originally isolated from a melanoma. The aims of this study were to determine: (i) whether HPV DNA could readily be demonstrated in skin tumors, as well as in perilesional skin, of immunocompetent patients using two polymerase chain reaction primer sets; (ii) the prevalence of infections in normal skin; and (iii) the prevalence of HPV 38 or HPV 38 related viruses in melanoma. The HPV types detected in lesions from renal allograft recipient were present not only in the perilesional skin and tumors of immunocompetent patients, but also in 35% of normal skin biopsies. HPV DNA was present in 13% of the melanoma samples, but none harbored HPV 38 DNA. We identified four putatively new HPV types. Infections with different types of human papillomavirus are widespread and often occur in clinically normal skin. In vitro studies are required to determine the specific molecular mechanisms by which these HPV types may be involved in the etiology of nonmelanoma skin cancer.
Adult↗
A putative human papillomavirus type 57 new subtype isolated from plantar epidermoid cysts without intracytoplasmic inclusion bodies.
Human papillomavirus type 60 (HPV-60) is the only virus type that has been identified in epidermoid cysts. In this study, HPV-57 DNA was found in three out of 18 plantar epidermoid cysts with different histological features from HPV-60-associated cysts, using PCR and Southern hybridization. The HPV-57-associated cysts had features resembling an HPV-2-specific cytopathic effect. The sequences of two HPV-57 DNA clones isolated from two patients were identical, but differed at some positions from those of HPV-57a and HPV-57b. This putative new subtype was tentatively designated as HPV-57c, and may be associated with plantar epidermoid cysts showing histological features resembling the HPV-2 cytopathic effect.
Amino Acid Sequence↗
A case of a human-papillomavirus-60-induced wart with clinical appearance of both pigmented and ridged warts.
Human papillomavirus (HPV) type 60 infection is histologically associated with characteristic homogeneous intracytoplasmic inclusion bodies. However, it remains unclear whether the virus is associated with cystic, pigmented or ridged plantar warts. We report a 51-year-old Japanese female with a HPV-60-induced plantar wart which showed the clinical appearance of both pigmented and ridged warts. Masson-Fontana staining revealed increased melanin granules in the epidermis of the wart. This observation suggests that HPV-60 may be associated not only with cystic warts but also with the specific morphology of ridged warts, and the biological disorder of hyperpigmentation may be controlled by additional unknown factors which differ from case to case.
Female↗
Identification of active substances from Streptomyces culture fluids using p53-independent expression of p21/WAF1/Cip1 gene and their mode of action.
An assay system was constructed to identify chemicals that have a potential to induce p21/WAF1 gene, a target of the tumor suppressor p53 critical for negative growth regulation. Screening of about 1300 culture fluids of Streptomyces resulted in identification of active substances which induced the p21 gene in a p53-independent manner; one was a mixture of four members of the actinomycin group, and the other was trichostatin A. Transcriptional regulatory regions of p21 gene for induction by actinomycin D and trichostatin A were determined by transient expression of luciferase constructs in cells which are p53-deficient (Saos-2) or express a mutated form of p53 (TMK-1). The essential transcriptional elements for the response to these drugs localize within 210 bp of the 5'-upstream region of human p21 gene, and Sp1 elements were determined to be critical for the induction. DNA-binding activity of Sp1 was not increased in cells treated with these drugs, but kinase inhibitors such as staurosporin and wortmannin inhibited the induction.
Cyclin-Dependent Kinase Inhibitor p21↗
Phylogenetic analysis of the human papillomavirus type 2 (HPV-2), HPV-27, and HPV-57 group, which is associated with common warts.
Human papillomavirus types 2 (HPV-2), HPV-27, and HPV-57, are three closely related viruses within the phylogenetic supergroup formed by the remotely related genital papillomaviruses. In contrast to this phylogenetic association, these three viruses are most often found in common warts at nongenital sites, but also occasionally in genital warts and mucosal lesions of the nasopharyngeal cavity. We studied the genomic diversity of HPV sequences in skin warts presumably caused by these viruses. These biopsies were sampled from 75 patients living in Germany, Japan, or Singapore. Among 27 warts with HPV-2, we found seven new genomic variants and among 32 with HPV-57, eight new variants. In both cases, we did not detect the original prototype genomes. In contrast, 13 of 16 warts with HPV-27 contained the prototype genome, and only one new variant was found in three patients. We did not find variants clearly intermediate between any two types, although HPV-2 and HPV-27 are among the most closely related of the extent HPV types. We also did not detect novel HPV types, although the samples were examined with polymerase chain reaction protocols that would have detected remotely related HPVs. So we propose that the phylogenetic group formed by HPV-2, HPV-27, and HPV-57 has no or only very are additional members. One of the HPV-57 variants found, HPV-57-G44, was most likely identical to the subtype HPV-57b, previously proposed to be associated with nasal neoplasia, but found here frequently in common skin warts. Our publication establishes a foundation for pathological and phylogenetic comparisons of HPV types in skin warts.
Base Sequence↗
Hair cycle-dependent expression of a nonspecific cross reacting antigen (NCA)-50/90-like molecule on follicular keratinocytes.
We found a carcinoembryonic antigen (CEA)-related antigen to be strongly expressed on a subset of follicular keratinocytes in normal human skin. The antigen was characterized immunohistochemically using a panel of antibodies against human CEA and CEA-related molecules. The expression of the antigen was studied in different phases of the hair cycle as well as in different hair types. Immunohistochemically, the antigen resembled the nonspecific crossreacting antigen (NCA) NCA-50/90 rather than true CEA. Its expression was limited to the innermost cells of the lowest segment of hair follicles in the catagen/telogen phases, being detected only where the hair shaft was attached to the epithelial hair sac in these phases. The same results were obtained for all hair types, i.e. terminal, vellus and intermediate hair. Coexpression of the antigen with both involucrin and differentiation-associated cytokeratins was noted in the cells in additional studies attempting to identify the exact subpopulations of follicular keratinocytes expressing the antigen in comparison with the expression of other functional markers. However, involucrin and the cytokeratins were also expressed in the upper segments of anagen as well as catagen/telogen hair follicles. Our findings strongly suggest that an NCA-50/90-like molecule is expressed cyclically on the innermost cells in the lowest segment of the outer root sheath only in catagen/telogen hair follicles. The cyclical expression in this specific subset of follicular keratinocytes only, in which the epithelial hair sac is attached to the hair shaft, may be associated with the stability of the attachment through the adhesive or, conversely, the repulsive function of CEA-related molecules, both of which have recently been proposed.
Animals↗
Adenovirus-mediated overexpression of IRS-1 interacting domains abolishes insulin-stimulated mitogenesis without affecting glucose transport in 3T3-L1 adipocytes.
Activated insulin receptor (IR) interacts with its substrates, IRS-1, IRS-2, and Shc via the NPXY motif centered at Y960. This interaction is important for IRS-1 phosphorylation. Studies using the yeast two-hybrid system and sequence identity analysis between IRS-1 and IRS-2 have identified two putative elements, the PTB and SAIN domains, between amino acids 108 and 516 of IRS-1 that are sufficient for receptor interaction. However, their precise function in mediating insulin's bioeffects is not understood. We expressed the PTB and SAIN domains of IRS-1 in HIRcB fibroblasts and 3T3-L1 adipocytes utilizing replication-defective adenoviral infection to investigate their role in insulin signalling. In both cell types, overexpression of either the PTB or the SAIN protein caused a significant decrease in insulin-induced tyrosine phosphorylation of IRS-1 and Shc proteins, IRS-1-associated phosphatidylinositol 3-kinase (PI 3-K) enzymatic activity, p70s6k activation, and p44 and p42 mitogen-activated protein kinase (MAPK) phosphorylation. However, epidermal growth factor-induced Shc and MAPK phosphorylation was unaffected by the overexpressed proteins. These findings were associated with a complete inhibition of insulin-stimulated cell cycle progression. In 3T3-L1 adipocytes, PTB or SAIN expression extinguished IRS-1 phosphorylation with a corresponding 90% decrease in IRS-1-associated PI 3-K activity. p70s6k is a downstream target of PI 3-K, and insulin-stimulated p70s6k was inhibited by PTB or SAIN expression. Interestingly, overexpression of either PTB or SAIN protein did not affect insulin-induced AKT activation or insulin-stimulated 2-deoxyglucose transport, even though both of these bioeffects are inhibited by wortmannin. Thus, interference with the IRS-1-IR interaction inhibits insulin-stimulated IRS-1 and Shc phosphorylation, PI 3-K enzymatic activity, p70s6k activation, MAPK phosphorylation and cell cycle progression. In 3T3-L1 adipocytes, interference with the IR-IRS-1 interaction did not cause inhibition of insulin-stimulated AKT activation or glucose transport. These results indicate a bifurcation or subcompartmentalization of the insulin signalling pathway whereby some targets of PI 3-K (i.e., p70s6k) are dependent on IRS-1-associated PI 3-K and other targets (i.e., AKT and glucose transport) are not. IR-IRS-1 interaction is not essential for insulin's effect on glucose transport, and alternate, or redundant, pathways exist in these cells.
3T3 Cells↗
[Clinico-pathological findings of gastrointestinal tract in the leprosy patients].
Endoscopic biopsies either or both for the stomach and colon looking for chronic gastritis and carcinomata followed by the histopathologic examinations of the mucosa were applied to long term leprosy inpatients and controls. 1) In chronic gastritis, glandular atrophy with cellular infiltration and submucosal fibrosis likewise intestinal metaplasia were predominated in the leprosy patients, in the comparison of the cases consisted of 30 leprosy patients and 16 controls. No characteristic changes for leprosy cases were encountered accordingly, however, as the sequences of the medications. 2) The observations of Helicobacter pylori (HP) by means of immunohistologic method were also applied to gastritic cases. However, the positive rates in the above groups were not much different one another. 3) The cases of gastric carcinoma were 14 during 14 years period, among which 9 showed protruded lesions indicating metaplastic changes as the precancerous lesion. 4) The carcinoma of the colon tended to be left sided in the leprosy patients.
Aged↗
Identification of HTLV-1-specific CTL directed against synthetic and naturally processed peptides in HLA-B*3501 transgenic mice.
Previous studies of CTL responses to influenza peptides in HLA single transgenic mice resulted in the identification of at most one immunodominant epitope. Since HLA-B*3501 is known to present multiple HIV-1-specific T cell epitopes we tested the cellular immune response of HLA-B*3501 transgenic mice to synthetic HTLV-1 peptides mixed with the lipohexapeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)propyl]cysteinyl-seryl-lysyl-l ysyl- lysyl-lysine, which is a biocompatible, Th-epitopeindependent adjuvant. Eleven of 37 tested HLA-B*3501 binding peptides mounted a CTL response after three in vitro stimulations. The HLA-B*3501 affinity of peptides correlated with their ability to induce CTL in HLA-B*3501 transgenic mice. Seven peptides derived from env-gp46 (VPSPSSTPLL, VPSSSSTPL, YPSLALAPH, and YPSLALAPA), pol (QAFPQCTIL), gagp19 (YPGRVNEIL), and tax (GAFLTNVPY) proteins induced peptide-specific CTL Bulk CTL generated by four peptides derived from env-gp46 (SPPSTPLLY, VPSPSSTPLLY, and VPSPSSTPLL) and pol (QAFPQCTILQY) killed peptide-pulsed and recombinant vaccinia-infected target cells. The latter peptides therefore present T-cell epitopes and are vaccine candidates for our transgenic mouse model.
Animals↗
Infection with GB virus C in leprous patients in Japan.
The detection of hepatitis C virus (HCV) in blood donors and patients with acute and chronic hepatitis has brought to the fore another virus or viruses which can be transmitted parenterally and induce liver disease. The RNA of a candidate virus designated GB virus C (GBV-C) was determined by the polymerase chain reaction with primers deduced from a helicase-like region in 229 leprous patients in Japan. GBV-C RNA was detected in 12 (5.2%) patients, and HCV RNA in 41 (18%). Three patients were coinfected with GBV-C and HCV. The nine patients infected with GBV-C alone had aminotransferase levels lower than the three patients with the mixed infection or the 38 patients infected with HCV only (P < 0.001). Sequence comparison within 100 base pairs in the helicase-like region suggested that two, three and three patients, respectively, would have been infected with three distinct strains of GBV-C. These results indicate that patients with leprosy are at increased risk for infection not only with HCV, but also with GBV-C, and that the infection with GBV-C alone would not induce hepatic injuries as severe as HCV infection.
Adult↗
Hepatitis C virus antibody, viral RNA and genotypes in leprous patients in Japan.
BACKGROUND/METHODS: Markers of hepatitis C virus infection were tested for in 229 patients with leprosy (male 154, female 75) in Japan. RESULTS: Antibody to hepatitis C virus by a second-generation enzyme immunoassay was detected in 68 patients (30%), and RNA of hepatitis C virus in 41 (18%), in prevalence rates much higher (p < 0.001) than those in matched controls (11/923 or 1.2% and 9/923 or 1.0%, respectively). Hepatitis C virus genotypes were II/1b in 37 (90%), III/2a in three (7%) and IV/2b in one (2%), in which II/1b was more frequently (p < 0.003) represented than in hepatitis C virus carriers without leprosy in Japan (520/767 or 68%). The 41 patients with hepatitis C virus viremia had serum transaminase levels significantly higher than those in the other 188 patients without viremia (p < 0.01). CONCLUSIONS: These results indicate that leprous patients confined in institutions are at high risk of hepatitis C virus infection, and that patients infected with hepatitis C virus should be monitored for liver function and placed on interferon therapy whenever required.
Biomarkers↗
An anatomical study on the forearm vascular system.
The purpose of the present study was to establish the clinicoanatomical basis for the radial forearm flap. We conducted a morphometric investigation on 52 Japanese cadavers, of forearm vessels, for use in free forearm flaps. The mean inner diameter of the cephalic and median cubital veins at the interepicondylar line was 1.9 +/- 1.2 mm and 1.8 +/- 1.1 mm, respectively. Mean inner diameter of the radial artery and venae comitantes 1 cm distal to the origins of the radial and ulnar arteries was 2.3 +/- 0.5 mm and 1.6 +/- 0.5 mm, respectively. The longest segment of a superficial vein was 28.7 +/- 4.6 cm, it was measured between the basilic vein 5 cm proximal to the interepicondylar line and the cephalic vein at Lister's tubercle. The length of the radial artery was 18.1 +/- 1.7 cm. There were fewer valves in the basilic vein and cephalic vein proximal to the median cubital vein and in the brachial veins than in the distal antebrachial veins. From these results some of the clinicoanatomical considerations of forearm vessels which will form the clinicoanatomical basis of the free forearm flap should be clarified.
Adult↗
Carcinoembryonic antigen and related antigens expressed on keratinocytes in inflammatory dermatoses.
Carcinoembryonic antigen (CEA) is recognized as being important not only as a tumour marker, but also as a cell adhesion molecule in the metastasis of malignant tumour cells, and in the development of inflammatory disorders in some organs. However, the role played by this antigen in inflammatory dermatoses has not been studied previously. To investigate the expression of CEA in inflamed skin, we performed immunohistochemical studies to detect the antigen in both frozen and formalin-fixed, paraffin-embedded biopsy specimens of inflammatory dermatoses, using five different monoclonal antibodies and one polyclonal antibody against human CEA or CEA-related molecules. CEA and CEA-related antigens were expressed by epidermal keratinocytes and by some infiltrating inflammatory cells in inflamed skin. The expression was observed primarily in the upper part of the malpighian layers of the epidermis. On the basis of the distribution of this expression, we suggest an additional role for CEA-related molecules, differing from their roles as tumour markers and adhesion molecules, namely that these molecules may be associated with the state of differentiation of epidermal keratinocytes. Unexpected expression of CEA-related antigens was seen on normal follicular keratinocytes. Thus, it is conceivable that CEA-related antigen may also play a role in the biology of hair follicles.
Antigens, Surface↗
Sweat duct milia--immunohistological analysis of structure and three-dimensional reconstruction.
The fine structure of sweat duct milia and the pathomechanism in their aetiology are still unknown. To examine the relationship and connection of milia to the sweat ducts as well as to the overlying epidermis, nine sweat duct milia, six incomplete and three complete, were studied by three-dimensional reconstruction (3DR) analysis based on photomicrographs obtained after histological and immunohistochemical staining with antibodies against carcinoembryonic antigen (CEA), cancer antigen (CA 50) and human cytokeratin 19 (CK 19). In both incomplete and complete milia, an eccrine duct expressing the antigens penetrated into the cyst wall at the centre of its base, formed a circular path within the wall, and opened into the inner cavity. The eccrine duct was mature in eight milia and immature in one. In the cyst wall, CA 50 and CK 19 were detected throughout the entire cyst except for the most apical portion of incomplete milia, where the cyst wall fused with the overlying epidermis which did not express any of the antigens. CEA was distributed mainly in the basal half of the milia. The finding that the path of the eccrine duct within the cyst wall is circular conflicts with the currently accepted concept of simple penetration of the eccrine duct into the wall, suggesting an acrosyringeal origin of the milia. An incomplete milium is the result of fusion between cells derived from an eccrine duct and those derived from the surrounding epidermis, while the formation of a complete milium does not involve this fusion.
Aged↗