bromochloroacetic-acid and Hypertrophy

To characterise the history, clinical and histopathological features of patients with bilateral nasal and temporal peripheral hypertrophic subepithelial corneal degeneration in a German population.. A detailed ophthalmological and dermatological history and clinical findings were recorded of nine patients with bilateral simultaneous nasal and temporal peripheral corneal degeneration from two centers in Germany. Excised tissues were studied by histopathology, immunohistochemistry, and transmission electron microscopy.. Foreign body sensation and need of artificial tear substitutes were the only symptoms reported regularly. Schirmer's and Jones-test were normal in all, but fluorescein break-up time of >10 s was found in five eyes of four patients. Best corrected visual acuity was reduced only under glare conditions. Corneal topography revealed irregular astigmatism in 13 of 14 eyes. Follow-up median time was 35 months. Most cases were stable within the follow-up period. Light and electron microscopy revealed the findings of superficial vascularised corneal hypertrophic scars, oxytatlan fibers, and discontinued Bowmans layer.. In this series of German patients with peripheral hypertrophic subepithelial corneal degeneration, the changes were predominantly located in the palpebral aperture and often present in both eyes. No associated surface disease could be established in this study. Light and transmission electron microscopy showed histological features that are similar to Salzmann's corneal changes without any inflammation. We hypothesise that light exposure and a localised limbal insufficiency could be involved in the pathogenesis.

Topics: Actins; Adult; Cornea; Corneal Dystrophies, Hereditary; Corneal Topography; Epithelium, Corneal; Female; Fibrillins; Humans; Hypertrophy; Immunoenzyme Techniques; Keratins; Male; Microfilament Proteins; Middle Aged; Vimentin; Visual Acuity

In the past, keratins have been established as structural proteins. Indeed, mutations in keratin 10 (K10) and other epidermal keratins lead to severe skin fragility syndromes. Here, we present adult K10-/- mice, which reveal a novel connection between the regulation of cell proliferation and K10. Unlike most keratin mutant mice, the epidermis of adult K10-/- mice showed no cytolysis but displayed hyperproliferation of basal keratinocytes and an increased cell size. BrdU labelling revealed a shortened transition time for keratinocytes migrating outwards and DAPI staining of epidermal sheets uncovered an impaired organization of epidermal proliferation units. These remarkable changes were accompanied by the induction of c-Myc, cyclin D1, 14-3-3sigma and of wound healing keratins K6 and K16. The phosphorylation of Rb remained unaltered. In line with the downregulation of K10 in squamous cell carcinomas and its absence in proliferating cells in vivo, our data suggest that the tissue-restricted expression of some members of the keratin gene family not only serves structural functions. Our results imply that the altered composition of the suprabasal cytoskeleton is able to alter the proliferation state of basal cells through the induction of c-Myc. A previous model based on transfection of K10 in immortalized human keratinocytes suggested a direct involvement of K10 in cell cycle control. While those experiments were performed in human cultured keratinocytes, our data establish, that in vivo, K10 acts by an indirect control mechanism in trans.

Topics: 14-3-3 Proteins; Animals; Biomarkers, Tumor; Cell Differentiation; Cell Division; Cytoskeleton; Epidermis; Exonucleases; Exoribonucleases; Gene Expression Regulation; Hyperkeratosis, Epidermolytic; Hypertrophy; Keratin-10; Keratin-6; Keratins; Mice; Mice, Knockout; Neoplasm Proteins; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Skin Diseases, Genetic; Tumor Suppressor Protein p53; Up-Regulation

In a previous report we have described the effects of expression of D-type cyclins in epithelial tissues of transgenic mice. To study the involvement of the D-type cyclin partner cyclin-dependent kinase 4 (CDK4) in epithelial growth and differentiation, transgenic mice were generated carrying the CDK4 gene under the control of a keratin 5 promoter. As expected, transgenic mice showed expression of CDK4 in the epidermal basal-cell layer. Epidermal proliferation increased dramatically and basal cell hyperplasia and hypertrophy were observed. The hyperproliferative phenotype of these transgenic mice was independent of D-type cyclin expression because no overexpression of these proteins was detected. CDK4 and CDK2 kinase activities increased in transgenic animals and were associated with elevated binding of p27(Kip1) to CDK4. Expression of CDK4 in the epidermis results in an increased spinous layer compared with normal epidermis, and a mild hyperkeratosis in the cornified layer. In addition to epidermal changes, severe dermal fibrosis was observed and part of the subcutaneous adipose tissue was replaced by connective tissue. Also, abnormal expression of keratin 6 associated with the hyperproliferative phenotype was observed in transgenic epidermis. This model provides in vivo evidence for the role of CDK4 as a mediator of proliferation in epithelial cells independent of D-type cyclin expression.

Topics: Animals; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinases; Cyclins; Epidermis; Fibrosis; Humans; Hyperplasia; Hypertrophy; Keratins; Mice; Mice, Transgenic; Proto-Oncogene Proteins; Retinoblastoma Protein; Skin; Skin Physiological Phenomena

To understand factors controlling endometrial responses to pregnancy, we have established a model using the baboon and examined the effects of infused human chorionic gonadotrophin (HCG) on the preparation of the luminal epithelium and stromal cell differentiation for the establishment of pregnancy.. The ultrastructure of endometrium from normal day 10 post-ovulation animals, cycling females treated with either HCG or FSH (control), and a day 15 pregnant animal has been compared.. In the control endometrium, the luminal epithelium was smooth and regular, with underlying spindle shaped stromal cells. In pregnancy, the luminal epithelium underwent a plaque reaction, while stromal cells enlarged and developed filament-rich cell processes. Infusion of HCG produced changes similar to those seen in pregnancy, with generalized plaque formation and stromal decidualization, while in the animal treated with FSH there was no response.. This study indicates that infusion of HCG into the uterus can duplicate many of the responses of the endometrium to pregnancy, although in this case the plaque reaction involved the whole of the luminal epithelium, rather than only the implantation site as in pregnancy.

Topics: Actins; Animals; Chorionic Gonadotropin; Decidua; Embryo Implantation; Endometrium; Epithelium; Female; Follicle Stimulating Hormone; Hot Temperature; Hypertrophy; Immunohistochemistry; Keratins; Microscopy, Electron; Ovulation; Papio; Pregnancy; Recombinant Proteins; Stromal Cells; Time Factors

Intradermal administration of concanavalin A, a potent T-cell mitogen, into an ear lap resulted in activation of chondrogenesis and stimulation of epidermis proliferation. This proliferation is sometimes invasive in character (pearls and epidermal nests form in the underlying connective tissue) but never turns into true cancerous lesions. This reaction can be delayed, but not prevented, by the prostaglandin inhibitor indomethacin. Stimulation of epidermis proliferation was also caused by administration of other immunomodulators, such as carrageenan type IV, Moloney sarcoma development, and rarely in the course of GvHr, but to much lesser degree than with concanavalin A. It is suggested that the same growth factors, which are mediators of local chondrocyte stimulation, are also mediators of keratinocyte activation.

Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bone Marrow Transplantation; Carrageenan; Chondrocytes; Concanavalin A; Drug Eruptions; Ear Diseases; Ear Neoplasms; Ear, External; Epidermis; Epithelium; Female; Graft vs Host Reaction; Hyperplasia; Hypertrophy; Indomethacin; Keratinocytes; Keratins; Male; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Mice, Inbred DBA; Mice, Inbred ICR; Mice, SCID; Moloney murine sarcoma virus; Precancerous Conditions; Sarcoma, Experimental; Transplantation, Heterotopic

Partial outlet obstruction of the rabbit bladder induces serosal thickening and smooth muscle (SM) hypertrophy. Within thickened serosa, submesothelial (mesenchymal) cells differentiate into SM cells after 30 days of obstruction[S. Buoro et al. Lab. Invest. 69, 589-602, 1993]. Here, we show that submesothelial cells transiently express keratin (K) 18 but not K8 soon after obstruction. We investigated a possible relationship between keratin expression and cell proliferation/differentiation in vivo and in vitro. The results of this study indicate that expression of K18 is spatiotemporally related to the pattern of cell proliferation with respect to the localization of an elastic membrane which divides the thickened serosa into an "extrinsic" and an "intrinsic" region. Moreover, K18 is not present in bladder mesenchyma during early development, indicating that its expression in the adult is not attributable to a dedifferentiation process. However, simultaneous K18, K8, and desmoplakin (DP) expression can be induced in normal and thickened serosa upon treatment with bromo-deoxyuridine. Our results indicate that K18 is a marker of proliferating mesenchymal cells in rabbit serosa, whereas the combined expression of K18, K8, and DP might be related to the hypothesized alterations in the stability of gene expression. A model is proposed in which keratin-containing submesothelial cells can act as a "transit" cell phenotype involved in both regenerating mesothelial cells and formation of SM cells.

Topics: Animals; Cell Differentiation; Cell Division; Cells, Cultured; Constriction; Cytoskeletal Proteins; Female; Hypertrophy; Intestinal Mucosa; Keratins; Male; Mesoderm; Muscle, Smooth; Rabbits; Serous Membrane; Urinary Bladder

Tonsillar abnormalities have been observed in patients with IgA nephropathy (IgAN). In addition, it has been suggested that reticulization of tonsillar crypt epithelium is important in tonsillar immunity. Therefore, we investigated reticulization of this area in patients with IgAN (14 cases) and compared results with those of control patients who exhibited recurrent tonsillitis or tonsillar hypertrophy (12 cases). Immunohistochemical staining of antikeratin antibody PKK1 was employed to visualize reticulization. Tonsils of controls showed well developed reticular crypt epithelia with lymphoepithelial symbiosis and the nonreticulated area was less than 7% of the total crypt epithelia per overall section. In IgAN tonsils, however, nonreticulated crypt epithelium was frequently observed and, in the advanced stage of IgAN, exceeded 50% of total crypt epithelia. The extent of glomerular damage in IgAN patients correlated significantly with the percentage of the area of nonreticulated crypt in palatine tonsils with a correlation coefficient of 0.91. Considered together with our finding that PKK1-positive epithelial reticular cells strongly expressed HLA-DR antigens in normal tonsils, the low level of reticulization in IgAN patients may induce the unusual immunity responsible for the pathogenesis of IgAN.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Child; Child, Preschool; Epithelium; Female; Glomerular Mesangium; Glomerulonephritis, IGA; HLA-DR Antigens; Humans; Hypertrophy; Immunohistochemistry; Keratins; Male; Middle Aged; Palatine Tonsil; Tonsillitis

The effect of sodium lauryl sulphate (SLS) on cytokeratin (CK) gene expression in hamster cheek pouch epithelium was studied with a hybridohistochemical technique. Using specific human anti-sense RNA probes, the plausible hamster mRNA counterparts for these human CK mRNAs were localized by detection of heterologous hybrids. In comparison with normal epithelium, the expression and distribution pattern of CK mRNAs in the hamster cheek pouch were obviously changed after application of SLS. There was a decreased expression of CK mRNAs in the hyperplastic basal layer, and increased expression in the hypertrophic granular layer. Strikingly, hybridization with the human CK 18 cRNA probe revealed an additionally expressed CK mRNA in the SLS-treated epithelium that was not found in the untreated epithelium. The present study indicates that cRNA probes for human CK mRNAs can be used successfully, not only to distinguish between different hamster CK mRNAs but also to investigate changes in CK gene expression upon the induction of non-neoplastic and neoplastic alterations in the hamster cheek pouch model. This may help elucidate the molecular changes involved in epithelial pathologies.

Topics: Animals; Cheek; Cricetinae; Detergents; Epithelium; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Histocytochemistry; Humans; Hybridomas; Hyperplasia; Hypertrophy; In Situ Hybridization; Keratins; Male; Mesocricetus; Mouth Mucosa; Mouth Neoplasms; RNA Probes; RNA, Antisense; RNA, Complementary; RNA, Messenger; Sodium Dodecyl Sulfate; Surface-Active Agents

The concept of epidermal architecture that depends on epidermal turnover time is described. The epidermal architecture is determined, not by a simple proliferative condition, but rather by an epidermal turnover time (that depends both on cell number as well as on the proliferative condition). This is in relation to 'keratinization process' that requires a definite time to be completed. Using the concept, hyperproliferative 'psoriasiform' epidermis and hypoproliferative 'atrophic' epidermis are naturally described.

Topics: Atrophy; Cell Count; Cell Division; Epidermal Cells; Epidermis; Hypertrophy; Keratins; Models, Biological; Psoriasis; Time Factors

Basic fibroblast growth factor (bFGF) can stimulate the proliferation and differentiation of keratinocytes, fibroblasts, and endothelial cells. These cells are involved during the healing of tympanic membrane (TM) perforations. Light and electron microscopy examinations were used to study the histology of TM healing after application of 400 ng of bFGF on the perforation. The progress of healing is accelerated, but the basic healing process is unchanged, i.e., epithelial proliferation first closes the perforation and is then followed by connective tissue growth. There is more connective tissue in the TM receiving bFGF, and extracellular fibers are better oriented. No significant increase of neoangiogenesis was detected in the treated TM. In the nonperforated area of treated TM, an extensive hyperplasia of the submucosal connective tissue is observed. These results demonstrate that bFGF can produce a TM scar containing more connective tissue, which may be of benefit in the prevention of atrophic healed TM.

Topics: Animals; Basement Membrane; Cell Division; Connective Tissue; Epithelium; Exudates and Transudates; Fibrin; Fibroblast Growth Factor 2; Fibroblasts; Hyperplasia; Hypertrophy; Keratins; Male; Microscopy, Electron; Neutrophils; Rats; Rats, Sprague-Dawley; Tympanic Membrane; Wound Healing

The expression of cytokeratins in the epithelium of the middle ear and external auditory meatus of the rat was studied on cryosections of ethylenediaminetetraacetic acid-decalcified specimens by use of a panel of monoclonal antibodies. The normal middle ear epithelium revealed a complex cytokeratin profile, including regional differences. The induction of sterile middle ear effusions resulted in increased cytokeratin expression. Infective effusions were accompanied by both quantitative and qualitative changes in the cytokeratin expression patterns. The differences observed between the cytokeratin profiles of external meatal skin and those of middle ear epithelium may form a useful tool for research into cholesteatoma development.

Topics: Animals; Antibodies, Monoclonal; Ear, Middle; Epithelial Cells; Hyperplasia; Hypertrophy; Immunohistochemistry; Keratins; Male; Mucous Membrane; Otitis Media; Rats; Rats, Inbred Strains

In a patient with progressive supranuclear palsy (PSP) and hypertrophy of the olives, neurons with different forms of argyrophilic degeneration were detected by means of Bodian's silver staining method, i.e., neurofibrillary tangle-bearing neurons in the basal ganglia and brain stem, ballooned argyrophilic neurons in the brain stem, and hypertrophied neurons in the olives. In these cells, the cytoskeleton was investigated to ascertain whether neurons with different cytoskeletal changes contained phosphorylated neurofilaments (P-Nf) in the perikaryon. This study, carried out using two monoclonal antibodies that recognize phosphorylated epitopes of the neurofilament high molecular weight subunits, showed that hypertrophied olivary neurons, most ballooned neurons and a small aliquot of tangle-bearing neurons were labelled. The immunostaining of hypertrophied and ballooned neurons was localized in the whole perikaryon and dendrites, whereas that of tangle-bearing neurons was confined to the tangle. These findings were reproduced in five additional patients (one with hypertrophy of the olives, four with PSP) and demonstrated that, in PSP, the mechanism responsible for tangle formation does not affect the ability of neurons to accumulate P-Nf. This fact suggested that perikaryonal P-Nf accumulation is likely to be part of the cell reaction to abnormal conditions affecting the neuronal cytoskeleton.

Topics: Brain; Cytoskeleton; Glial Fibrillary Acidic Protein; Humans; Hypertrophy; Immunohistochemistry; Intermediate Filaments; Keratins; Male; Middle Aged; Olivary Nucleus; Supranuclear Palsy, Progressive

The clinical and histopathological features of 12 female patients with Flegel's disease were studied. The onset of this dermatosis was delayed until adulthood. The eruption consisted of scaly papules 1-5 mm in diameter which developed principally on the lower legs, upper arms and pinnae. Histopathologically there were discrete foci of hyperkeratosis with some parakeratosis over an attenuated and partially spongiotic epidermis. A genetic influence in this disorder was suggested by its occurrence in sisters in two families and in a mother and daughter. Immunohistochemical and biochemical studies suggested that there is a disorder of keratinocyte proliferation in the disease.

Topics: Adolescent; Adult; Epidermis; Female; Humans; Hypertrophy; Keratins; Middle Aged; Skin Diseases

Groups of lactating mice received daily 9 intraperitoneal injections consisting of the following chemicals: sesame oil only or 10.0, 20.0 or 40.0 micrograms estradiol-17 beta or 250.0, 500.0 or 1000.0 micrograms chlordecone. Reproductive tracts and vaginal surface changes were examined in the neonates that were nursed by the treated lactating dams for 12 days. Ingestion of milk from dams treated with estradiol or chlordecone did not produce any toxic symptoms or mortality in the offspring. However, the neonatal reproductive tract weights and vaginal epithelium exhibited significant changes indicating the passage of these compounds in milk. The vaginal epithelium in the neonates that nursed the estradiol-treated dams exhibited mucification, keratinization, and desquamation. Neonates that ingested milk from chlordecone-treated dams exhibited similar but dose-dependent changes in the vaginal canals. However, the keratinized vaginal cells in these mice were morphologically different and lacked the well-developed microridge patterns on the cell surfaces that characterized keratinized cells in the estradiol group. The significance of these changes on the reproductive functions in adult animals are discussed in the text.

Topics: Animal Population Groups; Animals; Animals, Suckling; Cell Membrane; Chlordecone; Epithelium; Estradiol; Female; Hypertrophy; Insecticides; Keratins; Mice; Microscopy, Electron, Scanning; Microvilli; Pregnancy; Vagina

Effects of cyproterone acetate, a synthetic steroidal compound, on the reproductive organs of female rats have been investigated. This agent caused reduction of ovarian weights indicative of suppression of pituitary gonadotrophins. Oestrogenic nature of cyproterone acetate was investigated in intact and ovariectomized rats taking uterine weight and vaginal keratinization as an index of oestrogenicity. Cyproterone acetate in ovariectomized animals induced vaginal keratinization and increased the uterine weights. These effects were parallel to the effect of oestradiol dipropionate in ovariectomized animals, thus indicating oestrogenic activity of cyproterone acetate. We may conclude that the above compound caused antifertility effects due to its oestrogenic nature at the dose level of 2 mg/alternate day in rats when the compound was administered subcutaneously.

Topics: Animals; Atrophy; Body Weight; Castration; Cyproterone; Estradiol; Female; Fertility; Genitalia, Female; Hyperplasia; Hypertrophy; Keratins; Organ Size; Ovary; Rats; Reproduction; Uterus; Vagina

The number of epithelial cells per unit volume of tissue (NV) and the relative volume (VV) occupied by the spinous and basal layers of X-irradiated and non-irradiated rat-tail epidermis were studied using techniques of stereologic cytology. By a simple calculation, the absolute volumes of basal and spinous keratinocytes were determined in irradiated (and in non-irradiated, control) epidermis, 24, 48, 72 and 96 h after exposure to a single dose of 16 Krads. During this post-irradiation period, the absolute volumetric values of both basal and spinous keratinocytes increased gradually, reaching a three-fold increase 96 h after irradiation. At the same time, the relative volume of the spinous layer increased from 58% to 75% of the total epidermis, whereas the volume fraction occupied by the basal layer decreased from 20% to 16%. These findings support previous evidence that lethally and sublethally damaged keratinocytes are capable of a metabolic effort resulting in a cell hypertrophy which in some circumstances could lead to repair and recovery from radiation damage.

Topics: Animals; Cell Count; Epithelial Cells; Epithelium; Hypertrophy; Keratins; Microscopy, Electron; Rats; Rats, Inbred Strains; Skin; Tail; Time Factors

Topics: Animals; Cell Transformation, Neoplastic; Endometrium; Epithelium; Female; Hyperplasia; Hypertrophy; Intrauterine Devices; Keratins; Metaplasia; Ovarian Diseases; Ovary; Polyps; Rats; Time Factors; Uterine Diseases; Uterus

Topics: Adult; Aged; Autopsy; Child; Cholesteatoma; Chronic Disease; Connective Tissue; Ear, Middle; Epithelial Cells; Epithelium; Granulation Tissue; Humans; Hyperplasia; Hypertrophy; Keratins; Male; Metaplasia; Microtomy; Middle Aged; Mucous Membrane; Otitis Media; Staining and Labeling; Temporal Bone; Tympanic Membrane

Embryonic chick epidermis, if cultured for 4 days on a TH millipore filter overlying certain malignant dermal fibroblasts, shows abnormalities ranging from complete degeneration to hypertrophy and abnormal differentiation. The effect of the tumour cells is prevented if the thickness of the filter is doubled, to 50 μm., but not if a 25 μm.-thick membrane is coated with a thin collagen gel. When a semipermeable membrane is interposed between the cells and the epidermis, the latter does not degenerate, but keratinizes without showing the usual stages of differentiation.The malignant cells sometimes cause hypertrophy of the epidermis when cultured beneath the dermis of intact skin, but have no effect when grown on the peridermal surface of this tissue or of isolated epidermis.Freeze- or heat-killed dermal cells, whether normal or malignant, provide an unsuitable substratum for epidermal survival, possibly due to adsorption of intracellular constituents on to their surfaces.IT IS SUGGESTED THAT THE MALIGNANT FIBROBLASTS EXAMINED PRODUCE AT LEAST TWO SUBSTANCES HAVING AN EFFECT ON EPIDERMIS: one of small molecular size affecting differentiation, and a toxic macromolecule. A growth-promoting substance may also be produced by the cells of one subline.

Topics: Adsorption; Animals; Cell Differentiation; Chick Embryo; Collagen; Culture Techniques; Fibroblasts; Filtration; Freezing; Gels; Hot Temperature; Hypertrophy; Keratins; Membranes, Artificial; Mice; Neoplasms, Experimental; Skin