Biomedical subjects

K Jimbow

Publications and source records attributed to K Jimbow.

At least 73 records · Page 4Linked to original sources

PubMed1994

The synthesis of N-acetyl-4-S-cysteaminyl [U-14C]phenol as a basis for the development of an antimelanoma and melanoma-radioimaging agent.

This study reports the synthesis of 14C-labelled N-acetyl-4-S-cysteaminylphenol ([14C]N-Ac-4-S-CAP), a potent melanocytotoxic and anti-melanoma agent. A reaction of [U-14C]phenol with NH2CH2CH2S+ cation in HBr solution was used for the synthesis of (4-S-cysteaminyl[14C]phenol[14C]4-S-CAP). The excess cystamine was removed, and [14C]4-S-CAP and 2-S-cysteaminyl[14C]phenol ([14C]2-S-CAP) were separated on preparative thin layer chromatography. [14C]4-S-CAP was acetylated with acetic anhydride in pyridine and subsequently O-deacetylated with NH3 in methanol, resulting [14C]N-Ac-4-S-CAP (3.8% radiochemical yield; a sp. act. of 450 kBq/mumol; radiochemical purity > 99%).

Acetylation↗

PubMed1994

Role of gene expression and protein synthesis of tyrosinase, TRP-1, lamp-1, and CD63 in UVB-induced melanogenesis in human melanomas.

Using melanotic cells (SK-MEL-23 and G361) and amelanotic cells (C32 and SK-MEL-24) of human melanoma, this study examined whether UV-B irradiation has a direct stimulatory effect on the expression of genes involved in melanogenesis. Our initial screening of methylthiazol tetrazolium (MTT)-formazan formation assay indicated a low dose of ultraviolet (UV)-B irradiation, 2.5 and 5.0 mJ/cm2, can metabolically stimulate these cells. Repeated exposure of UV-B at 5.0 mJ/cm2 for seven consecutive days resulted in increased tyrosinase activity and melanin synthesis in SK-MEL-23 and G361 cells, but not in C32 and SK-MEL-24 cells. On reverse-transcription-polymerase chain reaction and immunoprecipitation studies, the two melanotic cell lines exhibited upregulated expression of mRNA and antigenic epitopes of tyrosinase, tyrosinase-related protein (TRP-1; gp75/HMSA-5), and lysosomal membrane associated protein (Lamp-1). The amelanotic cell line, C32, expressed the tyrosinase gene and protein constitutively but revealed no active tyrosinase or melanin synthesis even after UV-B exposure. Another amelanotic cell line, SK-MEL-24, exhibited no expression of tyrosinase gene and protein before and after UV-B exposure and, therefore, no melanin synthesis. Both C32 and SK-MEL-24 showed no gene or protein expression of TRP-1 before or after UV exposure, but upregulation of the Lamp-1 gene and protein expressions after exposure. We conclude that tyrosinase is the key enzyme responsible for UVB-induced melanogenesis. Both TRP-1 and Lamp-1 act together in melanogenesis, TRP-1 being essential and necessary. There is no change in the expression of CD63 lysosomal membrane protein at either the mRNA or protein level.

Antigens, CD↗

PubMed1994

High plasma level of a eumelanin precursor, 6-hydroxy-5-methoxyindole-2-carboxylic acid as a prognostic marker for malignant melanoma.

Melanin synthesis is a biologic property unique to the melanocyte. It is highly elevated in malignant melanoma with the production of both eumelanin (brown/black pigment) and pheomelanin (yellow/red pigment), dihydroxyindole (DHI) and cysteinyldopa (CD), respectively, being major precursors. Melanin metabolites are often released in the urine of patients with disseminated melanoma metastasis (melanuria). To establish a better method for the detection of occult melanoma this study compares the plasma levels of a pheomelanin metabolite, 5-S-CD, and a eumelanin metabolite, 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C), in melanoma and non-melanoma patients and correlates them with tumor thickness and melanoma metastasis. We found a) that the normal plasma levels of 5-S-CD and 6H5M12C are less than 2.22 ng/ml and 1.04 ng/ml, respectively; b) that the group with the normal 6H5MI2C plasma level does not have any metastasis, whereas a normal 5-S-CD level is seen in both non-melanoma and melanoma patients with and without metastasis; c) that a high plasma 6H5MI2C level is seen in all melanoma patients with tumor thickness more than 3.0 mm regardless of the presence or absence of metastasis, whereas in thinner melanoma patients this is seen only in positive metastasis group; and d) that all melanoma patients with positive metastases showed a high plasma 6H5MI2C level (more than 1.75 ng/ml). We conclude that the measurement of plasma levels of melanin metabolites provides a method for detecting occult melanoma metastasis and estimating the prognosis of melanoma patients, plasma 6H5MI2C level being more sensitive and reliable than that of 5-S-CD, and its increased level being a high risk factor.

Biomarkers, Tumor↗

PubMed1994

Molecular control of melanogenesis in malignant melanoma: functional assessment of tyrosinase and lamp gene families by UV exposure and gene co-transfection, and cloning of a cDNA encoding calnexin, a possible melanogenesis "chaperone".

Melanogenesis is a cascade of events significantly controlled by regulatory genes which are associated with the melanosomal membrane. This report introduces our current research efforts dealing with (a) the gene and protein expressions of tyrosinase and Lamp (lysosome-associated membrane protein) families by human melanoma cells after repeated exposures to UV light, (b) the coordinated alterations in the expression of the Lamp family gene and its encoding product after transfection of two genes of the tyrosinase family in human melanoma cells and (c) cloning and sequencing of a Ca(2+)-binding phosphoprotein, calnexin, which could be a candidate as a chaperone for sorting and maturation of tyrosinase and Lamp family glycoproteins in melanogenesis cascade. Our UV exposure study, as well as gene transfection and antisense hybridization experiments, has clearly indicated a marked and coordinated interaction of the Lamp-1 gene with the tyrosinase and TRP-1 genes in this process. We propose that melanogenesis is controlled at least by two major gene family products, i.e., (a) the tyrosinase family of tyrosinase, TRP-1 and TRP-2, and the Lamp family of Lamp-1, Lamp-2 and Lamp-3. These two gene families probably derived from primordial melanogenesis-associated genes which are common or closely related to each other.

Antigens, CD↗

PubMed1994

Coordinated mRNA and protein expression of human LAMP-1 in induction of melanogenesis after UV-B exposure and co-transfection of human tyrosinase and TRP-1 cDNAs.

In order to better understand the cascade of melanogenic events in melanocytes, this report has introduced our two recent approaches for the expression of melanogenesis/or melanosome-associated genes and encoded proteins in melanocytes (melanoma cells) after repeated exposure to UV-B and after cotransfection of two human genes, i.e., tyrosinase and tyrosinase-related protein-1 (TRP-1). Repeated exposure of UV-B (2.5-5.0 mJ/cm2) caused not only upregulation of tyrosinase and TRP-1 genes but also coordinated increase in the gene and protein synthesis expression of Lamp-1 (lysosome-associated membrane protein-1). When COS-7 kidney cells and amelanotic melanoma (C32 and SK-MEL-24) and melanotic melanoma (G361 and SK-MEL-23) cells were exposed to cotransfection of human tyrosinase and TRP-1 cDNAs, there was also an increased expression of Lamp-1 mRNA and protein along with tyrosinase activation and new melanin synthesis. Importantly, single transfectants of human tyrosinase cDNA revealed marked cellular degeneration, whereas this degeneration was not seen in single transfectants of TRP-1 cDNA or cotransfectants of human tyrosinase and TRP-1 cDNAs, indicating that TRP-1 prevented, along with Lamp-1, programmed death of melanocytes after transfection of tyrosinase gene. The coordinated expression of TRP-1 and Lamp-1 was further confirmed by antisense oligodeoxynucleotide hybridization experiment against Lamp-1 gene, showing the decreased expression of TRP-1 as identified by three different types of anti-TRP-1 monoclonal antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1994

Immunohistochemical detection of melanoma-associated antigens on formalin-fixed, paraffin-embedded canine tumors.

Seven monoclonal antibodies (Moabs), recognizing melanoma-associated antigens in human tissues, were evaluated for their ability to immunohistochemically stain formalin-fixed, paraffin-embedded canine melanomas. Only 2 Moabs, designated human melanosome-specific antigen (HMSA)-1 and HMSA-5, stained routinely processed canine melanomas, staining 21/35 (60%) and 24/35 (69%), respectively. Twenty-nine of 35 (83%) melanomas tested were stained if results of the 2 Moabs were combined. Monoclonal antibody HMSA-1 also stained neoplastic cells of 10/35 (29%) tumors of nonmelanocytic origin and some neurons and salivary gland epithelial cells in normal canine tissues. However, Moab HMSA-1 staining in the nonmelanocytic tumors, consisting of small, discrete periodic acid-Schiff-positive cytoplasmic droplets, was readily distinguishable from the diffusely granular, cytoplasmic staining of melanocytic tumors. In addition to melanomas, Moab HMSA-5 stained melanocytes and some melanin-containing tumor cells of a pigmented basal cell tumor and melanocytes in normal canine skin. Monoclonal antibodies HMSA-1 and HMSA-5 immunohistochemically identified the majority of canine melanomas, had limited and distinguishable staining in normal tissues and nonmelanocytic tumors, and therefore may be a useful adjunct for the diagnosis of canine melanoma in formalin-fixed, paraffin-embedded tissues.

Animals↗

PubMed1993

Identification of a cDNA coding for a Ca(2+)-binding phosphoprotein (p90), calnexin, on melanosomes in normal and malignant human melanocytes.

In order to have a proper biosynthesis and secretion of the melanin-pigment granules (melanosomes) the melanocyte may require a melanosome-associated molecule that provides a signal for assembly and organization of melanogenic enzymes and proteins within the compartment of melanosomes. This study reports the presence of a Ca(2+)-binding phosphoprotein, p90, which can be engaged in such melanogenic function, located on the melanosomal membrane of human melanocytes. A human melanoma cDNA expression library in lambda Zap II was screened with a rabbit polyclonal antibody raised against human melanosomes isolated from cultured human melanoma cells, SK MEL 23. A cDNA encoding a melanosomal protein, M(r) 90 kDa, was identified through this immunoscreening. A partial sequencing of nucleotides (822 bp from the N-terminal domain) of this clone (3.8 kb) and predicted amino acids showed more than 90% homology with dog calnexin, a previously reported endoplasmic reticulum (ER) transmembrane protein. A fusion protein of this p90 with beta-galactosidase expressed in Escherichia coli revealed both the immuno-cross-reactivity with anti-dog calnexin and anti-human melanosome antibodies and the Ca(2+)-binding property. Upon immunohistochemistry, the anti-dog calnexin antibody revealed the positive immunoreactivities with both normal and malignant human melanocytes, showing a much higher expression of antigenic epitope than nonmelanocytic human cells. The laser scanning confocal immunofluorescence, using an antibody against a human melanosome-specific antigen (HMSA-5), and immunoelectron microscopy, using immunogold, confirmed the major localization of anti-dog calnexin antibody epitope on the melanosomes and ER.

Amino Acid Sequence↗

PubMed1993

A murine monoclonal antibody, MoAb HMSA-5, against a melanosomal component highly expressed in early stages, and common to normal and neoplastic melanocytes.

The melanosome is a secretory organelle unique to the melanocyte and its neoplastic counterpart, malignant melanoma. The synthesis and assembly of these intracytoplasmic organelles is not yet fully understood. We have developed a murine monoclonal antibody (MoAb) against melanosomes isolated from human melanocytes (newborn foreskin) cultured in the presence of 12-O tetradecanoyl phorbol-13-acetate (TPA). This MoAb, designated HMSA-5 (Human Melanosome-Specific Antigen-5) (IgG1), recognised a cytoplasmic antigen in both normal human melanocytes and neoplastic cells, such as common and dysplastic melanocytic nevi, and malignant melanoma. None of the carcinoma or sarcoma specimens tested showed positive reactivity with MoAb HMSA-5. Under immunoelectron microscopy, immuno-gold deposition was seen on microvesicles associated with melanosomes, and a portion of the ER-Golgi complexes. Radioimmunoprecipitation analysis showed that the HMSA-5 reactive antigen was a glycoprotein of M(r) 69 to 73 kDa. A pulse-chase time course study showed that the amount of antigen detected by MoAb HMSA-5 decreased over a 24 h period without significant expression on the cell surface, or corresponding appearance of the antigen in the culture supernatant. This glycoprotein appears to play a role in the early stages of melanosomal development, and the HMSA-5 reactive epitope may be lost during subsequent maturation processes. Importantly, HMSA-5 can be identified in all forms of human melanocytes, hence it can be considered a new common melanocytic marker even on routine paraffin sections.

Animals↗

PubMed1993

Characterization of melanosome-associated proteins by establishment of monoclonal antibodies and immunoscreening of a melanoma cDNA library through an anti-melanosome antibody.

Monoclonal antibodies against melanosomal components (human melanosome specific antigens; HMSAs) have been developed in our laboratory. HMSA-1-4 recognizes structural matrix proteins of melanosomes. HMSA-5 is identical to TRP-1, equivalent to the b (brown) locus of murine melanocytes and expressed in early stages of melanosomal maturation. HMSA-6 is a protein associated with melanosomes but its role is still unclarified, and HMSA-7 is identical to the lysosomal protein CD63. We have also recently identified p90 calnexin-like, Ca(2+)-binding protein p97 melanotransferrin, and p64 beta-D-galactosidase-like protein associated with melanosomes through immunological screening of our melanocytes (melanoma cells) cDNA library. Approximately 150 genes and 60 loci are known to influence eye, skin and hair colour in mammals. Tyrosinase is a rate-limiting enzyme responsible for melanin synthesis. In addition, tyrosine-related proteins (TRPs) and their genes have been identified and cloned. Tyrosinase and TRPS (e.g., TRP-1; b-locus protein identical to HMSA-5 and TRP-2; dopachrome tautomerase) are synthesized according to underlying genetic programmes, and are up- and/or down-regulated to create various forms of abnormal melanin pigmentation. We herein propose the importance of investigating the role of non-tyrosinase related proteins such as those which we have recently identified.

Animals↗

PubMed1993

Development and characterization of a murine monoclonal antibody against phaeomelanin and its precursor 5-S-cysteinyldopa.

This study reports our success in developing a murine monoclonal antibody (mAb) against phaeomelanin and its major precursor, 5-S-cysteinyldopa (5-S-CD). A competitive enzyme-linked immunosorbent assay was developed and demonstrated that the new mAb, designated as 6D4 (IgG1, kappa), reacted with both 5-S-CD and phaeomelanin, but not with eumelanin. The concentrations required for 50% inhibition of 5-S-CD and phaeomelanin were 65 ng/ml and 95 ng/ml respectively. The minimal amount of 5-S-CD and phaeomelanin which could be detected by mAb 6D4 was approximately 5 and 6 ng/ml, respectively. The immunohistochemical assay indicated that the antigenic epitope(s) recognized by mAb 6D4 was localized in the cytoplasm of certain types of melanocytic tumours, such as superficial spreading melanoma.

Animals↗

PubMed1993

Melanin pigments and melanosomal proteins as differentiation markers unique to normal and neoplastic melanocytes.

This report introduces some aspects of our current basic research focus on the unique metabolic pathways within the melanocyte. Using this approach, we hope to gain a better understanding of the pathophysiology of malignant melanoma and develop early laboratory diagnostic tests for this disease. Specifically, we will discuss that: 1) the synthesis of pheomelanin is markedly increased in malignant melanoma and dysplastic melanocytic nevi; 2) high levels of metabolites of pheomelanin and eumelanin can be detected in the urine and blood of patients with metastatic melanoma; 3) this release of melanin metabolites appears to correlate with tumor thickness and tumor load, including the extent of metastasis; 4) the synthesis of melanosomal proteins also becomes aberrant in malignant melanoma; and 5) this abnormal melanosome synthesis can be utilized in the identification of antigenic epitopes that are uniquely expressed in malignant melanoma. We believe that this synthesis and secretion of abnormal melanin pigment and melanosomal proteins (human melanosome-specific antigen) would be useful for the development of early laboratory diagnostic and monitoring tools for malignant melanoma. In addition, we also report the detection of pheomelanin component in "normal" unexposed skin; however, the relative amount of pheomelanin in the skin does not reflect hair color (e.g., red hair). The nature of this pheomelanin component in the skin needs to be further clarified.

Animals↗

PubMed1993

Case report of Darier disease localized to the vulva in a 5-year-old girl.

A 5-year-old girl with Darier disease had numerous verrucous papules coalescing into plaques on both labia majora of approximately one year's duration. She was diagnosed as having genital warts, raising the suspicion of sexual abuse. Subsequently, a biopsy specimen from one of the vulvar lesions revealed histologic characteristics consistent with a diagnosis of Darier disease. The case is unusual for the age of onset and the site of initial involvement, and stresses the importance of including acantholytic disorders such as Darier disease in the differential diagnosis of a child with clinically verrucous lesions.

Biopsy↗

PubMed1993

cDNA-based functional domains of a calnexin-like melanosomal protein, p90.

We have recently identified a gene encoding a calnexin-like protein (p90) by the immunoscreening of a human melanoma cDNA library, using a rabbit anti-human melanosomal antibody. This p90 protein was highly expressed by human melanocytes and associated with melanosomal membrane and endoplasmic reticulum. In this study we report the computer analysis of the predicted amino acid sequence of this calnexin-like melanosomal protein. We found that p90 is a membrane-bound protein whose large N-terminal domain is located within the melanosomal compartment; its shorter C-terminal is exposed to the cytosol and separated by a short transmembrane region. This p90 protein was found to have consensus sequences of a Ca(2+)-binding loop and a protein kinase C phosphorylation site at the N-terminal domain. The C-terminal domain, on the other hand, contained sequences of a casein kinase II phosphorylation site and two protein kinase A phosphorylation sites. Such functional motifs could provide signal transduction across the melanosomal membrane, the reception of melanogenic protein via carriers at the melanosomal membrane and the translocation of melanosomes in the melanocyte.

Amino Acid Sequence↗

PubMed1993

Exploitation of pigment biosynthesis pathway as a selective chemotherapeutic approach for malignant melanoma.

Human malignant melanoma represents a difficult therapeutic challenge to both medical scientists and practicing physicians. However, the biologic uniqueness of the tumor may provide opportunities for exploitation in therapeutics. This study proposed to undertake a systemic approach to the chemotherapy of malignant melanoma based upon the uniqueness of pigment-cell metabolic pathway pertaining to conversion of tyrosine and dopa with subsequent formation of melanin by tyrosinase and its related enzymes. The sulphur homologue of tyrosine, cysteinylphenol (CP), its amine derivative, cysteaminylphenol (CAP), and their N-acetyl and alpha-methyl derivatives have been synthesized and tested in in vivo and in vitro melanocytotoxicity and antimelanoma effects. These phenolic thioethers (PTEs) and phenolic thioether amine (amides) (PTEAs), which are substrates of tyrosinase, showed significant cytotoxicity that is selective to melanocytes and melanoma cells. Most previous attempts to impair the melanin pathway as a therapeutic strategy have been of limited success because they have been directed to catecholic compounds that are unstable and insufficient in lethality at physiologically tolerable doses. By contrast, our approach relies on phenolic compounds, PTEs and PTEAs, which are more stable than catechols and become toxic only after oxidation by tyrosinase. We found PTEA as the most promising agent for the future development of chemotherapeutic agents. The possible biologic, chemical, and pharmacologic reactions of these synthetic compounds within the melanoma cells are studied and discussed.

Benzoquinones↗

PubMed1992

Polyethylene-glycol-mediated delivery of liposome-entrapped pigments into fibroblasts: experimental pigment cells as models for mutator phenotypes.

The role of epidermal melanin pigments in the development of skin cancer remains unclear. A new technique for the specific introduction of compartmentalized melanin into nonpigmented human fibroblasts through the use of liposomes and polyethylene glycol (PEG) is presented. The delivery of liposome-encapsulated material to cells was characterized by: (a) high efficiency of delivery through PEG-mediated endocytosis at 37 degrees C; (b) intracellular acidification of liposome entrapped pH-sensitive 8-hydroxypyrene-3,6,8-trisulfonic acid after delivery; (c) similar incorporation and acidification of apolipoprotein E-associated liposomes into fibroblasts via the low-density lipoprotein-receptor pathway; and (d) discharge into the extracellular space after incorporation. Similar experiments were carried out with melanin-containing liposomes that were used to introduce compartmentalized melanin into fibroblasts, through PEG-mediated delivery. These "artificial" melanocytes had functional analogies to genuine melanocytes in that (a) in both cell types melanin compartmentalization was at a lower pH; and (b) liposome contents were later expelled in analogy to the putative biological process of melanin expulsion from the melanocyte. The modified fibroblasts provided potential "mutator" phenotypes with specific melanin pigmentation, and established a new basis for studying the role of melanin pigmentation in cancer development.

Cell Compartmentation↗

PubMed1992

Selective in vivo and in vitro incorporation and accumulation of phenolic thioether amine into malignant melanoma and identification of a (58 kD) binding glycoprotein.

Our previous in vivo studies indicated that a phenolic thioether amine (PTEA), 4-S-cysteaminylphenol (CAP), selectively disintegrates melanocytes of black hair and skin, and inhibits the growth of murine and human malignant melanomas. To elucidate the mechanism of the in vivo melanocytotoxicity and anti-melanoma effect, this study examined the selectivity and specificity of PTEA incorporation into malignant melanoma cells using [14C]4(2)-S-CAP, and then identified a PTEA-binding protein through a ligand binding assay using [125I]-labelled cell lysates. Whole body autoradiography showed that [14C]4-S-CAP is selectively incorporated and accumulated into the eye and tumours of a B16 melanoma-bearing mouse. SK MEL 23 human melanoma cells also showed a steady accumulation of [14C]4-S-CAP (threefold at least up to 5 min) and of [14C]2-S-CAP (sevenfold up to 20 min), compared with that of HeLa cells and fibroblasts, which plateau at 5 min. Chromatography of 4-S-CAP on an affinity column (both CH- and CNBr-activated Sepharose 4B) identified a 58 kD protein in melanoma cells, which was present at very low levels in HeLa cells; this 58 kD protein was retained by both 4-S- and 2-S-CAP affinity columns, but not by columns of a phenolic thioether (cysteinylphenol: CP) or a phenolic thioether amide (N-acetyl-4-S-CAP), and could be retrieved by either 4-S or 2-S-CAP but not by CP and N-acetyl-4-S-CAP. This protein was glycosylated, and contained mannose residues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Reactivity of orthoquinones involved in tyrosinase-dependent cytotoxicity: differences between alkylthio- and alkoxy-substituents.

It may be possible to use the melanogenic pathway as a therapeutic targeting strategy for melanoma, and encouraging clinical pilot studies of 4-hydroxyanisole have led to the search for more active analogue substrates of tyrosinase. A recent study of a range of alkoxy- and alkylthio-phenol analogues of tyrosine has shown that sulphur-containing compounds exhibit different behaviour to that of similar oxygen-containing compounds, indicating modified reactivities of their corresponding tyrosinase-induced o-quinones towards crucial cellular targets, in particular, thiols. We have therefore examined by pulse radiolysis the reactivities of a group of unstable alkylthio- and alkoxy-substituted o-quinones towards the biologically relevant thiols, cysteine and glutathione. The o-quinones were generated by rapid (microsecond) one-electron oxidation of the corresponding stable synthesized catechols, forming semiquinones which disproportionated over milliseconds to o-quinones. The latter reacted with the thiols in a pH-dependent manner, indicative of increased nucleophilicity of the thiolate anions as compared with their protonated forms, with rate constants in the region of 10(5)-10(6) M-1s-1. At pH 7.2, within the physiological range, the alkylthio-substituted o-quinones reacted with the thiols approximately 5-10 times faster than the alkoxy-substituted o-quinones. The corresponding alkylthio-substituted phenols might, therefore, in principle, be expected to be more effective targeted anti-melanoma drugs than their alkoxy-substituted counterparts. NMR studies of the reactions of several of the quinones with cysteine indicate that, where addition occurs, the product is exclusively the 6-S-cysteinyl-4-substituted-catechol.

Cell Survival↗

PubMed1992

Confluent and reticulated papillomatosis: clinical, light and electron microscopic studies.

A case of a 17-year-old Japanese-Canadian boy with a 2-year history of skin lesions relevant to confluent and reticulated papillomatosis (CRP) is reported with electron microscopic findings. He had scattered skin lesions of brownish-colored, rough-surfaced, fine-scaled patches and plaques distributed on the nape, shoulders, and both flanks, extending to the chest and back. Importantly, they showed reticular or confluent arrangement. There was no family history of the same skin lesions. The histology showed epidermal papillomatosis and mild acanthosis with a marked hyperkeratosis. Electron microscopically, the skin lesions consisted of the following abnormal findings: (1) a marked alteration of cornified cell structures showing snake coil-like, or triangle-like stacks, (2) a marked increase in the number of lamellar granules in the granular layer, (3) an increased number of melanosomes in the horny layers, and (4) no significant fine structural changes of epidermal melanocytes. This is the first electron microscopic report on CRP suggesting that the pathophysiology of this disease is related to abnormal keratinocyte differentiation.

Adolescent↗