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Immunohistochemical demonstration of MAM-3 and MAM-6 antigens in normal human skin appendages and their tumors.

The expression of MAM-3 and MAM-6 antigens was immunohistochemically investigated on 110 tumors of human skin appendages. Forty-two samples from tumor-adjacent normal skin appendages were also studied. MAM-3 antigens, as detectable by monoclonal antibodies (MoAbs) 67D11, 115G3, and 115H10 were present in the inner layer cells but not in the outer layer cells of normal eccrine excretory ducts. Sporadic positivity was also found in cytoplasm of apocrine acini with 115G3, while 67D11 and 115H10 were negative. MAM-6 antigens, as detectable by the MoAbs 115D8, 115F5, 139H2, 140C1, and 126E7 were found in the secretory canaliculi of normal eccrine acini and within the apical lumina at the terminal portion of ducts. Apocrine acinar cells mainly exhibited an apical staining, but a focal supranuclear dot-like staining could also be observed. A foamy reaction pattern for MAM-6 was noted in mature sebocytes. However, none of the antigenic epitopes was expressed in normal squamous epithelium or hair follicles. In benign tumors, the staining patterns for both antigens, in general, resembled their distribution in the corresponding normal tissues. However, carcinomas originating from sweat glands, sebaceous glands, and the pilar apparatus expressed both antigens in a more irregular and heterogeneous pattern. This might preferably be explained by the loss of those mechanisms controlling the antigen expression in mature, functional tissues. Conclusions from these immunohistochemical studies with regard to the histogenesis mainly of the malignant skin appendage tumors should be drawn with caution.

Antibodies, Monoclonal↗

Immunohistochemical evidence of alpha-, beta- and gamma 3-melanocyte stimulating hormone expression in cutaneous malignant melanoma of nodular type.

Opiomelanocortins are formed after cleavage of the larger precursor molecule, proopiomelanocortin (POMC), which contains several peptide residues, sharing certain amino acid homology, including adrenocorticotrophic hormone (ACTH) and alpha-, beta- and gamma-melanocyte stimulating hormone (MSH). The expressions of alpha-, beta- and gamma 3-MSH in human cutaneous malignant melanoma of nodular type are demonstrated. For the MSHs, the immunolabelling was concentrated mostly in the tumour cellular cytoplasm, with occasional cells displaying a nuclear staining. Labelled tumour cells were dispersed throughout the epidermis and dermis as individual cells or in so-called 'pearl-like nests', most of which consisted mainly of round or oval shaped cells as well as a few pleomorphic or spindle-shaped cells. The fluorescence intensity seemed to increase in accordance with the development of the tumours. All cases examined were clearly stained with protein S-100, which provided us with a definite diagnosis. Considering the overall MSHs-related staining intensity of each section, the general perception we got was that the closer to the centre of the tumour parenchyma, the stronger was the staining and, furthermore the larger/more poorly differentiated the cells, the stronger was the staining. We also found the MSHs expressions to appear in the peripheral part of the tumour and the perilesional tissues including epidermis, sweat glands, sebaceous glands as well as hair follicles. Neurohypertrophic features were encountered including increases in both the number of nerve fibres and their diameter. Our results presented here strongly support the viewpoint earlier proposed that MSH peptides, by an autocrine and/or paracrine production from melanoma cells, are engaged in the regulation of melanogenesis, growth and proliferation of the tumour cells. We also conclude that, although alpha-, beta- and gamma 3-MSH peptides do not provide as high a sensitivity for diagnosis as protein S-100, they appear as useful markers for supportive diagnosis and assessment of malignant melanoma.

Adult↗

Epidermal keratinocyte stem cells: their maintenance and regulation.

The epidermis is a stratified epithelium consisting of interfollicular regions and appendages (hair follicles, sweat glands, sebaceous glands). The dominant cell type (the keratinocyte) is arranged in groups of cells termed epidermal proliferative units (EPUs), and one centrally-located clonogenic stem cell is ultimately responsible for replacing the remainder of the cells in the unit. Evidence is reviewed which indicates that the epidermal Langerhans' cell (ELC), and the cells comprising the dermis, may modify the keratinocyte microenvironment to create stem cell 'niches' and cellular diversity within the basal layer.

Animals↗

Expression of ras proto-oncogene related protein p21 in normal human skin and cutaneous tumours.

The cellular proto-oncogene, ras, is known to play an important role in the regulation of cell growth and proliferation in normal and malignant conditions. The present study was undertaken to immunohistochemically examine the expression of ras protooncogene product p21 in normal human skin and some cutaneous tumours. In normal skin, the expression of p21 was found in sweat glands, sebaceous glands, capillary endothelium, and smooth muscles, while epidermis was devoid of reaction product. Keratoacanthoma and the granular cells of verruca vulgaris were immunoreactive to the antibody for p21. Bowen's disease and squamous cell carcinoma were positive for p21, but basal cell carcinoma and seborrheic keratosis were negative. In mammary and extramammary Paget's diseases, the immunoreactivity was inconsistent. The expression of p21 in malignant melanoma cells was intense, whereas normal melanocytes and nevus cells were devoid of the expression. These results suggest that the expression of p21 does not correlate with nuclear anaplasia and malignant behaviour of cutaneous tumours.

Bowen's Disease↗

A membrane protein preferentially expressed by a subpopulation of immature lymphoid cells, epidermal basal keratinocytes, and other epithelial cells.

A murine monoclonal antibody, designated EL-1, was raised by immunization with a human malignant T cell line. It reacted specifically with a membrane antigen expressed on T and B lymphoblastoid cell lines, a subpopulation of normal thymocytes and bone marrow lymphocytes, lymphocytes from a subset of patients with non-B, non-T cell acute lymphoblastic leukemia or T cell acute lymphoblastic leukemia and epithelial stem cells. The latter reactivity was especially striking in the skin, where only basal epidermal keratinocytes and epidermal appendages, including eccrine sweat glands, sebaceous glands and hair follicles, stained positively. A human epidermoid carcinoma cell line was also stained by EL-1. Suprabasilar keratinocytes and acellular keratin did not stain. However, in vitro proliferating fetal lung fibroblasts stained positively. Membrane immunoprecipitation analysis demonstrated that the antigen recognized by antibody EL-1 is a single protein of molecular weight 105 kilodaltons which did not change with exhaustive chemical reduction. Metabolic radiolabeling studies demonstrated that this protein is synthesized by the cell and not merely taken up from the culture medium. This antibody can be useful in studying keratinocyte differentiation in epidermal malignancies and normal skin.

Animals↗

[Generalized argyrosis].

For many years a 52-year-old patient suffering from duodenal ulcer had taken a silver-containing preparation, the total quantity of silver ingested in this manner amounting to about 35 g. 18 years after the first manifestation of duodenal ulcer a dermatologist diagnosed argyria and confirmed this by biopsy. After acute coronary failure with marked nicotine abuse autopsy revealed granulated deposits of silver in the corium, particularly on elastic fibres, at the sweat glands, sebaceous glands and hair follicles. There were no deposits in the epidermis. Dense silver deposits were also seen in the walls of most of the blood vessels, in the basal membranes of the renal glomeruli, of the choroid plexus and of the seminiferous tubules, as well as in the portal fields. Definite intracellular deposits occurred in macrophages only. The metal was found only rarely in epithelial basal membranes. Generalised argyria does not entail any pathological implications and is considered to be intractable.

Anti-Ulcer Agents↗

VAMP8/endobrevin as a general vesicular SNARE for regulated exocytosis of the exocrine system.

The molecular mechanism governing the regulated secretion of most exocrine tissues remains elusive, although VAMP8/endobrevin has recently been shown to be the major vesicular SNARE (v-SNARE) of zymogen granules of pancreatic exocrine acinar cells. In this article, we have characterized the role of VAMP8 in the entire exocrine system. Immunohistochemical studies showed that VAMP8 is expressed in all examined exocrine tissues such as salivary glands, lacrimal (tear) glands, sweat glands, sebaceous glands, mammary glands, and the prostate. Severe anomalies were observed in the salivary and lacrimal glands of VAMP8-null mice. Mutant salivary glands accumulated amylase and carbonic anhydrase VI. Electron microscopy revealed an accumulation of secretory granules in the acinar cells of mutant parotid and lacrimal glands. Pilocarpine-stimulated secretion of saliva proteins was compromised in the absence of VAMP8. Protein aggregates were observed in mutant lacrimal glands. VAMP8 may interact with syntaxin 4 and SNAP-23. These results suggest that VAMP8 may act as a v-SNARE for regulated secretion of the entire exocrine system.

Animals↗

Basement membrane laminin and type IV collagen in various benign and malignant adnexal tumors of the skin: an immunohistochemical study.

Thirty benign and seven malignant adnexal tumors of the skin and one lymph node metastasis were stained for laminin and type IV collagen with rabbit antibodies against the human basement membrane (BM) proteins using the immunoperoxidase technique. Fifteen of the benign sweat gland, sebaceous gland, and hair follicle tumors showed a continuous and distinct BM around the tumor aggregates. The cylindromas and eccrine spiradenomas seemed to produce excessive amounts of BM material, part of which was seen as amorphic patches within the tumor cell clusters, whereas the trichofolliculomas, trichoepitheliomas, and pilomatrixomas showed an absence of BM from many areas. In syringomas, in addition to the tubular structures surrounded by a continuous BM, undifferentiated cell nests containing granular BM material were present. They probably represent primitive structures obtaining during early development into tubules. The seven malignant tumors and the only metastasis studied here all contained small, narrow strips of BM material extracellularly between the infiltrating tumor clusters. Only in two cases was faint staining for laminin found within the cells. The pepsin pretreatment of the formalin-fixed, paraffin-embedded samples had most probably degraded the intracytoplasmic BM material in most cases. The BM defects were found to be associated with malignancy and low differentiation of the adnexal skin tumors, as reported previously for other tumor types, but a partial loss of BM was also associated with high differentiation in some benign adnexal tumors.

Adenoma↗

Immunohistochemical localization of lysyl oxidase in normal human skin.

Lysyl oxidase (EC 1.4.3.13), a copper-dependent enzyme which catalyses the formation of aldehyde cross-links, and acts primarily on collagen and elastin, is known to be increased during wound healing and in fibrotic disorders including liver cirrhosis and atherosclerosis, and to be decreased in some hereditary connective tissue diseases and in malignant cell lines. A recent study showed that lysyl oxidase might possess tumour suppressor activity as an antioncogene for ras. Little is known about the localization of this enzyme in human skin. In this study, we determined immunohistochemically the localization of lysyl oxidase in normal skin of young and elderly subjects obtained from sun-exposed and unexposed regions of the body. All skin samples tested had similar distributions of lysyl oxidase. The enzyme was present both extracellularly and intracellularly. Extracellularly, a few granular aggregates of immunoreactants were observed along collagen and elastic fibres. These granules were more common in the adventitial portion of the dermis than in the reticular portion. Of all sun-exposed and unexposed regions studied, the skin of the face displayed the greatest amount of extracellular immunoreactants. Immunopositive granules were observed intracellularly in fibroblasts, vascular endothelial cells, sweat glands, sebaceous glands, arrector pili muscles and some keratinocytes. These findings provide evidence that, as suggested in recent reports, lysyl oxidase may have a variety of intracellular functions.

Adolescent↗

Viral antigen distribution in organs of cattle experimentally infected with rinderpest virus.

The distribution of viral antigen in various organs of four approximately 10-month-old castrated male Friesian cattle experimentally infected with a highly virulent strain of rinderpest virus was studied. A monoclonal antibody with genus-specific reactivity for morbilliviruses was applied in an indirect immunoperoxidase method performed on formalin-fixed, paraffin-embedded tissue sections. Rinderpest viral antigen was located mainly in the cytoplasm of the epithelial cells of the digestive, respiratory, and urinary tracts, as well as in the cells of endocrine glands (adrenal, thyroid) and exocrine glands (salivary glands, sebaceous glands, exocrine pancreas). Furthermore, different types of cells in lymphatic organs contained rinderpest viral antigen. In contrast to the documented results of studies carried out with other morbilliviruses, tissues of the central nervous system did not contain viral antigen. Various types of epithelial and lymphoreticular cells are the main targets of a virulent strain of rinderpest virus in vivo.

Animals↗

[Familial amyloidotic polyneuropathy type IV (Finnish type)--the first description of a large kindred in Japan].

Familial amyloidotic polyneuropathy type IV, one of the hereditary systemic amyloidoses with an autosomal dominant trait, is clinically characterized by cranial neuropathy and corneal lattice dystrophy. Recent biochemical studies have indicated that the amyloid fibril protein in FAP IV is related to gelsolin, an actin-modulating protein. Cases were clustered in the Finnish population and only a few cases have been reported from other populations. Here we described a large kindred with FAP IV as the first report in Japan. This family comprises 42 members in three generations with 14 affected individuals. We examined 7 patients at the age ranging from 43 to 80 years. All cases have corneal lattice dystrophy type II. The disease begins with slowly progressive facial weakness in the fifth or sixth decade of life and consequently the V, XII, IX and X cranial nerves become involved. Peripheral neuropathy of the extremities remained mild until late of life. Microscopy of skin biopsy samples showed deposits of amyloid around the eccrine glands, sebaceous glands, epidermal-dermal junction and blood vessel walls. Immunohistochemistry of the skin revealed the immunopositive material against a monoclonal antibody to gelsolin in the amyloid deposits. Molecular analysis of the gelsolin gene is now in progress.

Adult↗

[Gene delivery system based on low molecular weight polyethylenimine and its transfection activity in the skin tissue].

Low molecular weight polyethylenimine (LMW-PEI) was linked to an expressing plasmid contains a green fluorescence protein (GFP) reporter gene and effective gene transfer was observed in CM7221 cell line tested. We examined the relationship among the molecular weight, structure of PEI and their transfection activity and cytotoxicity on CM7221 cell line. We also examined the position and continuance time of the GFP reporter gene expressed in the skin tissue of mouse. Results showed that LMW-PEI/DNA complexes led to high levels of expression in the CM7221 cell line (about 55%). However, with the increasing of PEI molecular weight, the transfection activity of PEI was decreasing. There was an increasing cytotoxicity with the larger PEI molecules. Further research showed that LMW-PEI induced a significant and long-lasting (7 days) expression of the GFP reporter gene in the hair vesicle, sweat, gland, sebaceous gland in the mouse skin tissues. The LMW-PEI described here is a new, highly efficient and non-cytotoxic vector. It would be a useful non-viral vector for gene delivery technology, particular useful as simple skin-specific vehicles of therapeutic genes.

Animals↗

Immunohistochemical detection of the Ca antigen in normal and tumor tissues of humans by use of Ca1 monoclonal antibody.

The Ca1 monoclonal antibody was used to detect Ca antigen in paraffin sections with the use of a two-stage indirect immunoperoxidase technique. A range of normal and malignant human tissues was examined. The antibody reacted with squamous cell carcinomas, small cell carcinomas, adenocarcinomas, ductal carcinomas, and anaplastic carcinomas from gastrointestinal, lung, and breast tissues. Melanomas were negative. Reactivity was also observed against normal tissues: urinary transitional epithelium, fallopian tube epithelium, breast ducts, sweat glands, sebaceous glands, alveolar epithelium, bile duct, gallbladder, kidney tubules, and some digestive tract epithelial cells. Although the study confirms earlier reports that Ca1 is a marker for some normal, nonciliated epithelial cells and for epithelial and some other cancers, a more widespread distribution for normal tissues was found.

Antibodies, Monoclonal↗

[Distribution of elastic bodies (elastic globes) in healthy human skin. Studies with a dense grid].

Since the turn of the century, there have been descriptions of corpuscular structures in the human skin. These are situated at the epidermal-corial junction zone. They can be visualized well with resorcinol-fuchsin staining according to Weigert. They may attain forensic significance in the topographic assignment of isolated skin fragments to certain body regions. The research results available so far, which are in some cases contradictory, were checked and the investigations were continued. A total of 584 skin punch samples were taken from the trunk and limbs of a 39-year-old male corpse. Of these, a total of 1752 paraffin serial sections (resorcinol-fuchsin staining) were prepared and investigated for the occurrence of elastic bodies. The investigation essentially showed that in almost all serial sections, elastic bodies were found to have a frequency concentration at points on the limbs. It could not be established that there was a sharp separation of skin areas containing elastic globes and skin areas free of elastic globes. The distribution of elastic bodies is evidently subject to a pattern of its own, which does not display any interrelationships with that of the skin appendages (apocrine and eccrine sweat glands, sebaceous glands, and male body hair). Because the skin of the trunk and the limbs is relatively regularly interspersed with elastic globes, there can only be used in connection with other features (e.g. thickness of the epidermis, skin appendages) to assign isolated skin fragments to certain regions of the body.

Adult↗

[Detection of hepatoid glands and distinctive features of hepatoid acinus].

In the 1920s-1930s, skin glands of a new type, hepatoid glands, were described in 13 mammal species (Rodentia, Canidae, and Bovidae). The hepatoid glands resemble sebaceous glands in their morphology, bur radically differ from them in specific structure of the acinus and another type of secretion. Later, these data either could not be confirmed or were considered insignificant and the hepatoid glands were described as modified sebaceous glands, glands with uncertain function, or modifications of epidermis. Based on the studies of various hepatoid glands in 22 species of Carniviora and Artiodactyla, the authors described in detail the characteristic features of the hepatoid acinus, which allow a precise discrimination of hepatoid and sebaceous glands. Extracellular secretory canaliculi have been described in the hepatoid glands, as well as the richness of hepatoid glands in protein, distribution of hydrophobic lipids in certain hepatoid glands, and formation of excretory ducts and cysts. The hepatoid glands are a source of great amounts of protein secreted in the merocrine way; the secretory substance of some of these glands has a strong odor.

Animals↗

Sebaceous cell carcinoma of the parotid gland.

Sebaceous cell carcinoma of the parotid gland is a rare lesion. A review of the English literature reveals nine previously reported cases. Two cases are presented in which the tumor was originally diagnosed as mucoepidermoid carcinoma. Aggressive treatment of the recurrence, which was subsequently recognized as sebaceous cell carcinoma has resulted in apparent cure. Histologic features and possible histogenesis are discussed.

Adenoma, Pleomorphic↗

[Lectin histochemical studies on the scent gland in the Syrian hamster and Mongolian gerbil].

The scent gland and ordinary sebaceous gland of Syrian hamsters and Mongolian gerbils were studied using lectin histochemistry. Male scent glands were larger in size than those of female in both species, but in histochemistry there was no distinct difference between both sexes. Histologically, the scent gland of Syrian hamsters had a strong resemblance to ordinary sebaceous glands, compared to that of Mongolian gerbils. Since the duct of Syrian hamsters was very short, it is difficult to distinguish the duct from the infundibulum. The duct and infundibulum of Mongolian gerbils were larger in diameter than those of Syrian hamsters. The duct widely opened to dermis. Seven lectins (ConA, RCA I, PNA, SBA, UEA-I, DBA and WGA) were used in this study. All of them labelled the differentiated cells of acinus in Syrian hamsters, although SBA did not label those cells in Mongolian gerbils. The cells of the duct in Syrian hamsters and Mongolian gerbils were not labelled with SBA. Ordinary sebaceous glands in both species were labelled with all seven lectins. Lectin-binding patterns of scent glands and sebaceous glands were similar in Syrian hamsters. While, in Mongolian gerbils, SBA-binding patterns were different between scent and sebaceous glands. Histologically, the scent gland of Syrian hamsters resembles the sebaceous gland. Therefore, there is a possibility that the scent gland of Syrian hamsters still provides some properties similar to sebaceous gland.

Animals↗

[Lectin histochemical studies on the musk gland in the house musk shrew (Suncus murinus)].

The musk gland of the adult house musk shrews (Suncus murinus) of both sexes was studied lectin histochemically. The musk gland was a kind of scent gland, consisted of congregation of branched or unbranched simple tubuloalveolar gland holocrine in nature and was attached by an apocrine gland-like structure (sweat gland) in the deeper layer of its periphery. Acinar cells of the musk gland were distinguishable into three type from basal to luminal parts of the acinus; immature cells, mature cells and degenerating cells. There was no histological difference between both sexes. Lectin-binding pattern of the musk gland was examined in comparison with that of the sweat gland and ordinary sebaceous gland by histochemical staining techniques using seven lectins: ConA, RCA I, PNA, SBA, UEA-I, DBA, WGA, WGA and PNA labelled the duct of the musk gland more intense than the acinus. Several lectins showed a tendency to label the cells situated near the luminal surface more intense than those near the basement membrane in both the acinus and duct of the musk gland. In the sweat gland and ordinary sebaceous gland, the lectin-binding pattern was different with each other and from that in the musk gland. These findings suggest that the musk gland, sweat gland, and ordinary sebaceous gland are different to each other in nature of cells and the secretion.

Animals↗