bromochloroacetic-acid and Vitamin-A-Deficiency

Topics: Animals; Antibodies, Monoclonal; Cell Differentiation; Cells, Cultured; Epithelium; Humans; Keratins; Models, Biological; Molecular Weight; Skin; Skin Diseases; Vitamin A Deficiency

Vitamin A deficiency or benzo(a)pyrene instillation into tracheas of Syrian golden hamsters causes squamous metaplasia of tracheobronchial epithelium, normally a mucous secretory tissue. In the present studies, we have employed a tracheal organ culture system and have reproduced the in vivo phenomenon of squamous metaplasia during culturing under vitamin A free conditions as well as after carcinogen treatment. The squamous metaplasia induced by vitamin A deficiency, both in vivo and in vitro, was accompanied by an overall increase in keratin synthesis. Vitamin A deficient tracheas were shown to contain keratins of 50, 48, 46.5 Kd detected with the antibody AE1, and 58, 56 and 52 Kd detected with AE3. These proteins were either absent or present in much less quantity in control tracheas. In deficient tracheas 60 kd keratin was found to be located specifically in squamous suprabasal cells, and 55 and 50 Kd keratin proteins were found in a greatly expanded basal cell compartment. Following carcinogen exposure, the appearance of 60 kd keratin and the enhanced expression of 50 and 55 Kd keratins preceded the squamoid metaplastic response as detected morphologically. Both the keratin changes and the morphological changes were prevented by retinoid treatment.

Topics: Animals; Carcinoma, Squamous Cell; Cell Differentiation; Cricetinae; Epithelial Cells; Epithelium; Keratins; Mesocricetus; Metaplasia; Organ Culture Techniques; Trachea; Vitamin A; Vitamin A Deficiency

Topics: Animals; Cell Division; Humans; Keratins; Lysosomes; Membranes; Mucins; Protein Biosynthesis; Rats; RNA; Skin; Skin Diseases; Vitamin A; Vitamin A Deficiency

Topics: Cell Division; Humans; Keratins; Oral Manifestations; Vitamin A Deficiency; Wound Healing

To determine the role played by keratinocyte transglutaminase (TG1, TG(K)) in the abnormal keratinization of the cornea.. Vitamin A-deficient rats were produced as a model of severe dry eyes, and the expression of the mRNA and the enzyme activity of TG1 were examined in the corneas. The envelope proteins and keratins of cornified cells were also examined immunohistochemically.. The expression and enzyme activity of TG1 mRNA on the ocular surface were significantly upregulated as the vitamin A deficiency developed. As the TG1 expression was upregulated, involucrin, loricrin, and keratin 10 began to be expressed on the epithelial cells of the cornea.. Upregulation of TG1 expression followed by the appearance of the envelope proteins and keratin10 in cornified cells indicated that TG1 is involved in the abnormal keratinization of the cornea.

Topics: Animals; Blotting, Northern; Cornea; Disease Models, Animal; Dry Eye Syndromes; Epithelial Cells; Gene Expression Regulation, Enzymologic; Immunoenzyme Techniques; Keratin-10; Keratins; Membrane Proteins; Protein Precursors; Rats; Rats, Sprague-Dawley; Retinaldehyde; RNA, Messenger; Transglutaminases; Up-Regulation; Vitamin A; Vitamin A Deficiency

The suggested function of cellular retinol-binding protein type I [CRBP(I)] is to carry retinol to esterifying or oxidizing enzymes. The retinyl esters are used in storage or transport, whereas oxidized forms such as all-trans or 9-cis retinoic acid are metabolites used in the mechanism of action of vitamin A. Thus, high expression of human CRBP(I) [hCRBP(I)] in transgenic mice might be expected to increase the production of retinoic acid in tissues, thereby inducing a phenotype resembling vitamin A toxicity. Alternatively, a vitamin A-deficient phenotype could also be envisioned as a result of an increased accumulation of vitamin A in storage cells induced by a high hCRBP(I) level. Signs of vitamin A toxicity or deficiency were therefore examined in tissues from transgenic mice with ectopic expression of hCRBP(I). Testis and intestine, the tissues with the highest expression of the transgene, showed normal gross morphology. Similarly, no abnormalities were observed in other tissues known to be sensitive to vitamin A status such as cornea and retina, and the epithelia in the cervix, trachea and skin. Furthermore, hematologic variables known to be influenced by vitamin A status such as the hemoglobin concentration, hematocrits and the number of red blood cells were within normal ranges in the transgenic mice. In conclusion, these transgenic mice have normal function of vitamin A despite high expression of hCRBP(I) in several tissues.

Topics: Animals; Cervix Uteri; Coloring Agents; Cornea; Epithelium; Female; Humans; Immunohistochemistry; Intestinal Mucosa; Intestines; Keratins; Male; Mice; Mice, Transgenic; Muscle, Smooth; Phenotype; Retina; Retinol-Binding Proteins; Retinol-Binding Proteins, Cellular; Testis; Tritium; Vitamin A; Vitamin A Deficiency

Retinoic acid is necessary for the growth and differentiation of organisms and exerts its molecular actions by binding to specific nuclear receptors that belong to the thyroid-steroid hormone receptor superfamily. Steroids and retinoids control the differentiation of the female reproductive epithelia: estrogen maintains the squamous differentiation of vaginal and ectocervical epithelia, whereas retinoic acid maintains the simple columnar endocervical and uterine epithelia. These lining epithelia transform into a squamous metaplastic phenotype in vitamin A-deficient animals. Furthermore, mortality due to vitamin A deficiency is usually attributed to infection resulting in part from dysfunction of the protective epithelia.. Our objective was to test the hypothesis that estrogen depletion might change the squamous metaplastic response to vitamin A deficiency and affect animal survival.. We used female SENCAR mice maintained on a purified vitamin A-deficient diet containing either 0 or 3 microg retinoic acid/g diet. Mice were either ovariectomized or intact. Squamous cells arising in the normally simple columnar epithelium of the endocervix and uterine cavity were monitored by keratin 5 expression with immunohistochemistry.. Ovariectomy did not change the time to onset of vitamin A deficiency. It increased the number of squamous metaplastic cells and prolonged survival in mice consuming a vitamin A-deficient diet by as much as 40%.. Factors other than epithelial differentiation per se control survival outcome of vitamin A-deficient mice. The results also show a significant increase in longevity of vitamin A- deficient mice when ovariectomized.

Topics: Animals; Epithelium; Female; Immunohistochemistry; Keratins; Metaplasia; Mice; Mice, Inbred SENCAR; Ovariectomy; Uterus; Vitamin A Deficiency

Steroid hormones and retinoids are powerful regulators of normal epithelial differentiation and function in the mouse female reproductive tract, where their actions are mediated by nuclear receptors. The expression pattern, heterodimeric interactions, and availability of ligand of these transcription factors are thought to contribute to the biological response. Estrogen (E2) induces proliferation and squamous differentiation of the cervical and vaginal epithelium during the mouse estrous cycle, while progesterone and retinoids maintain the simple columnar epithelium of the endocervix and uterine horns. We wanted to investigate whether retinoid receptors are responsive to estrogen status during cervical epithelial differentiation induced by a single dose of estrogen in ovariectomized adult mice. Northern blot analysis demonstrated a prolonged induction of RXR alpha and RAR gamma gene expression by E2 in the mouse cervix and vagina. When the induction of RXR alpha and RAR gamma was compared to genes known to be responsive to E2, including estrogen receptor (ER) and c-fos, RXR alpha was induced within 0.5 h of hormone treatment, while RAR gamma induction was evident by 4 h. The induction of these retinoid receptors suggests that they may be implicated in epithelial growth and differentiation in response to E2. Moreover, potential heterodimeric interactions among these receptors indicate that normal, cyclical epithelial differentiation results from the interplay of these molecules. Using in situ hybridization analysis, RXR alpha transcripts were localized preferentially in the basal cells, while ER mRNA was expressed throughout the epithelium of the ectocervix and vagina. Furthermore, ER transcripts were highly expressed in the stratified squamous foci induced by mild vitamin A depletion in the columnar epithelium of the endocervix and uterine horns. Therefore, the induction of RXR alpha and RAR gamma by E2 and their expression pattern in relation to ER suggest that they are needed to coordinate specific genetic programs that result in cervical epithelial growth and differentiation.

Topics: Animals; Cell Differentiation; Cervix Uteri; Epithelial Cells; Epithelium; Estradiol; Female; Gene Expression Regulation, Developmental; Keratins; Mice; Mice, Inbred BALB C; Ovariectomy; Phenotype; Proto-Oncogene Proteins c-fos; Receptors, Estrogen; Receptors, Retinoic Acid; Retinoic Acid Receptor gamma; Retinoid X Receptors; RNA, Messenger; Transcription Factors; Vagina; Vitamin A Deficiency

When a subareolar breast abscess (SBA) is incised and drained, an extraordinarily high frequency of recurrence is noted.. To develop a pathogenesis-based treatment plan, 24 women with a total of 84 abscesses were monitored.. In nine women SBA was under the left areola, under the right, in 7 and in eight the SBA occurred either simultaneously or sequentially under both areolae. In 11 of 24 patients a chronic lactiferous duct fistula also existed. In four of 24 patients four SBAs were treated with antibiotics; alone; all recurred. In 16 of 24 patients initial treatment was incision and drainage plus antibiotics; all recurred. When the abscess plus the plugged lactiferous duct was excised, there were no recurrences; however, in four patients a new abscess in a different duct occurred, which was treated by en bloc resection of all subareolar ampullae, without further recurrence. Patients with a fistulous tract had the fistula, its feeding abscess, and its plugged lactiferous duct excised, without recurrence. In first time SBA the organism was usually staphylococcus; in recurrences mixed flora was isolated. Pathologic findings ranged from squamous metaplasia with keratinization of lactiferous ducts to chronic abscess.. The cause of SBA is plugging of lactiferous duct within the nipple by keratin. To prevent recurrence the abscessed ampulla with its plugged proximal duct needs excision.

Topics: Abscess; Adult; Anti-Bacterial Agents; Breast; Combined Modality Therapy; Cutaneous Fistula; Disease Susceptibility; Female; Humans; Keratins; Mastitis; Metaplasia; Middle Aged; Nipples; Recurrence; Smoking; Staphylococcal Infections; Vitamin A Deficiency

Previous studies suggest that impression cytology may be a reliable test to detect mild xerophthalmia in young children. The present study was conducted to assess Vitamin A nutriture in 150 preschool children through a multi-approach, wherein the correlation of impression cytology, with other indicators of Vitamin-A status was examined. A close correlation between keratinization of buccal mucosal cells and vitamin A deficiency even in subclinical states has been noted.

Topics: Case-Control Studies; Child, Preschool; Female; Humans; India; Infant; Keratins; Male; Mouth Mucosa; Staining and Labeling; Vitamin A; Vitamin A Deficiency; Xerophthalmia

We describe an animal model to induce the histogenesis of squamous metaplasia of the cervical columnar epithelium, a condition usually preceding cervical neoplasia. This model is based on dietary retinoid depletion in female mice. Control sibling mice fed the same diet but with all-trans-retinoic acid (at 3 micrograms/g diet) showed the normal endocervical epithelial and glandular columnar morphology, typical of a simple epithelium without subcolumnar reserve cells. The stratified squamous ectocervical epithelium of these mice fed all-trans retinoic acid showed intense immunohistochemical staining in basal and suprabasal cells with mono-specific antibodies against keratins K5, K14, K6, K13, and, suprabasally, with antibodies specific for K1 and K10. At the squamocolumnar junction, the adjacent columnar epithelium (termed "suprajunctional") did not show staining for K5, K14, K6, K13, K1, and K10 but specifically stained for keratin K8, typical of simple epithelia and absent from the adjacent ectocervical squamous stratified lining (termed "subjunctional"), in striking contrast. Sections of the squamocolumnar junction from mice kept on the vitamin A-deficient diet for 10 weeks showed suprajunctional isolated patches of reserve cells, proximal and distal to the junction. These cells were detected prior to any symptoms of vitamin A deficiency, such as loss of body weight or respiratory discomfort. The subcolumnar reserve cells induced by vitamin A deficiency displayed positive staining for K5 and K14. As deficiency became severe, the reserve cells occupied the entirety of the suprajunctional basement membrane. This epithelium eventually became stratified and squamous metaplastic, the squamocolumnar junction was no longer discernible, and the entire endocervical epithelium and the endometrial glands lost K8 positivity, while acquiring K5, K14, K6, K13, K1, and K10 keratins typical of the ectocervix under normal conditions of vitamin A nutriture. Vitamin A deficiency also altered keratin expression and localization in squamous subjunctional epithelium. In situ hybridization studies for K1 and K5 mRNA showed their major site of expression at the basal (K5) and immediately suprabasal (K1) cell layers. The localization of both K5 and K1 proteins in these same cell layers, and above, is consistent with transcriptional regulation of these keratins. Early vitamin A deficiency caused the appearance of single subcolumnar reserve cells expressing K5 mRNA. After these ce

Topics: Animals; Carcinoma, Squamous Cell; Cervix Uteri; Diet; Disease Models, Animal; Epithelium; Female; Immunohistochemistry; In Situ Hybridization; Keratins; Metaplasia; Mice; Mice, Inbred BALB C; Mice, Nude; Phenotype; Precancerous Conditions; Retinoids; RNA, Messenger; Tretinoin; Uterine Cervical Neoplasms; Vitamin A Deficiency

Normal epithelial cell differentiation is characterized by the production of distinct cytokeratin proteins. It is well known that epithelia of several organs show squamous metaplasia in a vitamin A-deficient status. It is not yet known whether these histological changes are concomitant with a change in cytokeratin expression. Therefore, 3-week-old female rats (BN/BiRij) were fed a vitamin A-deficient diet for 8 weeks. The cytokeratin expression in epithelia of various organs was monitored immunohistochemically during the induction of vitamin A deficiency. Therefore, monoclonal antibodies specific for human cytokeratin 4, 5, 5 + 8, 7, 10, 14, 18 and 19 were used. In a normal vitamin A status, the distributional pattern for the different cytokeratins in rats was similar to that reported for human tissue. No change in cytokeratin expression was seen in trachea, skin, liver and colon at any time point studied. Squamous metaplasia in urinary bladder and salivary glands was observed after six weeks on the vitamin A-deficient diet. This was concomitant with a substitution of cytokeratins 4, 5 + 8, 7, 18 and 19 by cytokeratin 10. The latter cytokeratin is specific for keratinized squamous epithelium. A change in cytokeratin expression was observed in bladder, ureter, kidney, salivary glands, uterus and conjunctiva before histological alterations appeared. In conclusion, the changes in cytokeratin expression observed under vitamin A deficiency in epithelia in vivo are in agreement with those described in other studies for epithelial cells in vitro. The changes in cytokeratin expression and the subsequent differentiation into squamous cells occurs in basal cells of the bladder but not in transitional cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cell Differentiation; Epithelium; Female; Gene Expression Regulation; Keratins; Metaplasia; Organ Specificity; Rats; Rats, Inbred BN; Vitamin A; Vitamin A Deficiency

We induced vitamin A depletion to define early and late changes during the histogenesis of squamous metaplasia of hamster tracheal epithelium. An early change is the "minimal morphological change" (MMC), in which the mucociliary epithelium is separated from the basement membrane by a continuous layer of basal cells. Immunohistochemistry showed an exclusive localization of the keratins K5 and K14 in basal cells of normal and MMC epithelia. At the MMC stage no staining was observed above the basal layer with antibodies to K5, but upon progression of the lesion to a squamous focus all cells from basal to terminally differentiated were positive for K5 and K14. In contrast, when we used antibodies to the keratins K6 or K13 all cells were negative in the normal epithelium and in the MMC epithelium. Successive layers of suprabasal squamous cells found in squamous metaplasia failed to express normal epidermal differentiation marker keratins K1 and K10 but expressed the proliferation marker keratin K6 and the internal stratified epithelium keratin K13, not normally found in the epidermis or in the trachea. Hamster tracheal epithelial cells could be maintained in culture in serum-free medium for at least 4 weeks in the presence of retinoic acid (RA). In non-RA-containing medium, cells from vitamin A-deficient hamsters showed markedly reduced growth and an increase in the expression of keratins K5, K6, K13, and K14. Since our previous work had implicated retinoids in the control of cell adhesiveness, we were interested to find out whether changes in cell adhesion occur in vitamin A-deficient hamster tracheal epithelial cells, compared to normal cells. Functional assays demonstrated that hamster tracheal epithelial cells, obtained from non-RA-treated tracheas or maintained in culture, displayed reduced attachment to laminin, compared to RA-treated cells. Immunofluorescence studies did not show a decrease either in the alpha 6 integrin subunit, which was localized in the basal aspect of basal cells, or in basement membrane laminin. However, the expression of laminin-binding protein 37 decreased as the epithelium changed from pseudostratified to stratified. Therefore, a coordinated pattern of changes in keratin gene expression, as well as in the expression of laminin-binding protein 37, the precursor to the cell surface laminin receptor 67LR, and in adhesive properties takes place in tracheal epithelium when its phenotype changes from mucociliary to the preneoplastic s

Topics: Amino Acid Sequence; Animals; Antibodies; Blotting, Western; Cell Adhesion; Cell Adhesion Molecules; Cells, Cultured; Cricetinae; Epithelium; Fibroblasts; Immunohistochemistry; Keratins; Laminin; Male; Mesocricetus; Metaplasia; Molecular Sequence Data; Protein Binding; Trachea; Tretinoin; Vitamin A Deficiency

Changes in keratin expression were documented in cultures of hamster tracheal epithelial (HTE) cells exposed to vitamin A (retinol 10(-6) M) and benzo[a]pyrene (B[a]P), two agents known to affect the differentiation of tracheal epithelial cells in vivo. Keratin protein patterns were determined after 10 days in culture in the presence and absence of B[a]P in order to determine whether the expression of these proteins was altered by this carcinogen. HTE cells maintained in the presence of vitamin A expressed four simple epithelial keratins (7,8,18 and 19) while vitamin A deficient HTE cells expressed four additional cytokeratins (5,6,14 and 17). No effect of B[a]P on keratin expression was observed in vitamin A treated cells. However, vitamin A deficient HTE cells exposed to B[a]P (0.05-10 micrograms/ml) demonstrated a decrease in the expression of the four differentiation-related keratins while the simple epithelial keratins appeared to be unaffected. These observations were verified at the RNA level employing Northern blot analysis using cDNA probes for human keratins 5,6 and 14. Results demonstrate that B[a]P alters the expression of differentiation-related genes, the cytokeratins, in cell types known to develop into tumors of the respiratory tract.

Topics: Animals; Benzo(a)pyrene; Blotting, Northern; Cells, Cultured; Cricetinae; DNA Probes; Epithelial Cells; Epithelium; Humans; Keratins; RNA, Messenger; Trachea; Vitamin A; Vitamin A Deficiency

Hamster tracheal epithelial (HTE) cells maintained in primary culture show the induction of specific keratin species under vitamin A-deficient conditions. A comparison was made between the morphology and the expression of keratins in HTE cells in vivo and in primary culture with and without vitamin A. HTE cells cultured in serum-free, vitamin A-supplemented medium formed a simple cuboidal, ciliated monolayer and produced four simple epithelial keratins (7, 8, 18, and 19). In contrast, vitamin A-deficient HTE cells, which were squamous-like and stratified in culture, produced a more complex keratin pattern, with the induction of four additional keratin species (5, 6, 14, and 17). A keratin pair whose expression serves as a marker of stratified epithelia was induced, as well as a single keratin species unique to lesions of squamous metaplasia in vitamin A-deficient hamster tracheal organ cultures. Thus it appears that HTe cells retain the ability to respond to a deficiency in vitamin A through squamous differentiation and increased keratin production when removed from the intact organ and maintained in primary culture in a chemically defined medium. This system may be useful for the study of mechanisms underlying the squamous differentiation of respiratory epithelial cells in the development of bronchogenic tumors.

Topics: Animals; Cell Differentiation; Cells, Cultured; Cricetinae; Epithelial Cells; Epithelium; Female; Fluorescent Antibody Technique; Gene Expression Regulation; Keratins; Mesocricetus; Phenotype; Trachea; Vitamin A; Vitamin A Deficiency

In a defined culture system for hamster tracheal explants, the activity of 12 different retinoids was evaluated for reversal of keratinization induced by exposure to the carcinogen, benzo[alpha]pyrene (BP-HTOC assay). The effects of retinoids in this system were compared to those in a defined culture system for tracheal explants from vitamin A-deficient hamsters (standard-HTOC assay). In both assays, all-trans-retinoic acid (RA) and 13-cis-RA were the most active retinoids. For RA and 13-cis-RA, the values of ED50 determined in the BP-HTOC bioassay were 4 x 10(-12) and 1 x 10(-11) M, respectively, whereas the corresponding values in the standard HTOC assay were 2 x 10(-11) and 3.3 x 10(-10) M. For all 12 retinoids, the ED50 values from the BP-HTOC were lower than those from the standard-HTOC assay, and there was also a statistically significant correlation between the rank-ordering of ED50 values from the 2 assays. Among 3 N-(retinoyl)amino acids examined in both assays, N-(retinoyl)leucine was the most active, N-(retinoyl)phenylalanine the least active, and N-(retinoyl)alanine intermediate. Among a novel series of bifunctional retinoic acid analogues, the dicarboxyl derivative was the most active. On the basis of these results, the BP-HTOC assay appears to be one of the most sensitive assays for retinoids yet developed. This assay is an appropriate model for evaluating the chemopreventive potential of new retinoids in vitro.

Topics: Animals; Benzo(a)pyrene; Cricetinae; Culture Techniques; Epithelium; Keratins; Mesocricetus; Metaplasia; Retinoids; Trachea; Vitamin A Deficiency

Adult mouse epidermis contains up to 11 distinct keratin polypeptides, as resolved by two-dimensional gel electrophoresis. These include both basic (Type II; 67-, 65-, 63-, 62-, and 60-kDa) and acidic (Type I; 61- to 59-, 54-, 52-, 49-, and 48-kDa) keratins that exhibit multiple isoelectric forms. Several, but not all, of these keratins, identified by immunoblotting, were found to be actively synthesized in the skin when assayed in short-term pulse-labeling experiments. When compared to the adult, newborn mouse epidermis expresses fewer keratin subunits. However, greater amounts of keratins associated with differentiated suprabasal cells and stratum corneum, which is more pronounced morphologically in the newborn, were identified. We also observed strain-specific differences in the expression of a Type I acidic keratin. This 61-kDa (pI, approx. 5.3) keratin was produced exclusively by the CF-1 mouse and, based on peptide mapping, appeared to be related to the acidic 59-kDa keratin that was identified in this strain as well as all other mouse strains. The 61-kDa keratin was not expressed in vitamin A-deficient animals, suggesting that its appearance may be related to a retinoid-dependent posttranslational modification. In comparison to keratin expression in vivo, primary mouse keratinocyte monolayer cultures maintained in low Ca2+ (less than 0.08 mM) did not express the terminal differentiation keratins of 67-kDa (basic) or 59-kDa (acidic), although enhanced synthesis of the 60-kDa (basic) and the 52-kDa and 59-kDa (acidic) keratins associated with proliferation were observed. In addition, a subpopulation of nonadherent cells was continuously produced by the primary keratinocyte cultures that expressed the 67-kDa (basic) keratin specific for terminal differentiation. When the keratinocyte cultures were induced to terminally differentiate with Ca2+, the overall pattern of keratin expression was not changed significantly. Taken together, these results provide further evidence for the variable nature of keratin expression in mouse epidermal keratinocytes under different growth conditions.

Topics: Aging; Animals; Cell Differentiation; Cell Line, Transformed; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Epidermal Cells; Epidermis; Female; Immunologic Techniques; Isoelectric Point; Isotope Labeling; Keratins; Male; Mice; Mice, Inbred Strains; Mice, Nude; Peptide Mapping; Species Specificity; Sulfur Isotopes; Vitamin A Deficiency

Using immunohistochemical techniques, the keratin expression patterns in basal and columnar cells (mucus-producing and ciliated cells) were investigated in tracheal organ cultures. Tracheas were from either hamsters fed a control diet or from hamsters fed a vitamin A-deficient diet; tracheas from the latter group were treated in vitro with all-trans retinol. In tracheas from hamsters fed a control diet, basal cells generally reacted with the RCK102 antibody and columnar cells with the RGE53 and the HCK19 antibodies, and both basal and columnar cells were recognized by the RCK105 antibody. The squamous cell cytokeratin 10 (detected by the RKSE60 antibody) was not expressed in cultured tracheas from hamsters fed a normal or a vitamin A-deficient diet. In the course of the in vitro period a number of keratins were "switched on" or "switched off" in both basal and columnar cells. In tracheas from vitamin A-deprived hamsters the RCK102 antibody clearly recognized basal cells and cigarette smoke condensate-induced proliferating basal cells, whereas the RGE53 antibody reacted with mucus-producing and ciliated cells. During organ culture foci of columnar epithelial cells expressed basal cell properties (detected with the RCK102 antibody) after all-trans retinol treatment and were found negative for the RGE53 antibody. Furthermore, it appeared that the RGE53-negative columnar cells contained periodic acid-Schiff-positive mucous granules. These findings indicate that basal cells may differentiate into columnar cells. Tracheal epithelium did not appear to co-express vimentin next to keratins during organ culture, which may be due to the intact three-dimensional organization present in these organ cultures.

Topics: Animals; Antibodies, Monoclonal; Cells, Cultured; Cricetinae; Cytoskeleton; Epithelium; Female; Histocytochemistry; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Mesocricetus; Pregnancy; Trachea; Vimentin; Vitamin A Deficiency

Keratin expression in hamster tracheal epithelium was investigated during organ culture in serum-free, hormone-supplemented medium using monospecific monoclonal antibodies. Generally, tracheal basal cells expressed keratins detected by antibodies RCK102 and RCK103, while columnar epithelial cells were stained positively by RGE53, RCK103, RCK105 and HCK19. Metaplastic squamous cell foci reacted with antibodies RKSE60, RCK103 and HCK19. Early metaplastic alterations were more clearly RKSE60-positive than the mature lesions. In the vitamin A-depleted tracheas basal cells were clearly RCK102-positive. Superficial cells in the central part of areas of squamous metaplasia induced by cigarette smoke condensate expressed the basal cell keratins, and were negative for the columnar cell keratin 18 detected by the RGE53 antibody. This finding suggests that in cigarette smoke condensate-induced squamous metaplasia basal cells play an important role. The mucus-producing cells at the edges of metaplastic squamous cell foci expressed the keratins specific to columnar cells. Cigarette smoke condensate exposure accelerated epithelial keratinization compared to the vitamin A-depleted epithelium. It was concluded that not only small mucous granule cells, but also basal cells are involved in the development and maintenance of induced squamous metaplasia in tracheal epithelium. Furthermore, in vitro vitamin A-depleted epithelium did not coexpress vimentin in addition to the different keratins.

Topics: Animals; Antibodies, Monoclonal; Cells, Cultured; Cricetinae; Epithelium; Immunohistochemistry; Keratins; Mesocricetus; Nicotiana; Plants, Toxic; Smoke; Trachea; Vitamin A Deficiency

Tracheas from vitamin A-deficient hamsters in organ culture in vitamin A-free medium developed squamous metaplasia. Addition of retinyl acetate to the medium prevented squamous metaplasia and a mucociliary epithelium was maintained. Indirect immunofluorescent staining with antikeratin antibodies AE1 and AE3 indicated positive reactions with epithelium of tracheas either cultured in vitamin A-free or retinyl acetate (RAc)-containing medium. The "stratum corneum"-like squames in metaplastic tracheas were strongly stained by AE3. Immunoprecipitation of cytoskeletal extracts from [35S]methionine labeled tracheas with a multivalent keratin antiserum indicated that the concentration of keratins synthesized in tracheas cultured in vitamin A-free medium was greater than that observed in tracheas cultured in the presence of RAc. In addition, new species of keratin were expressed in tracheas cultured in RAc-free medium. Alterations in the program of keratin synthesis were clearly detectable after 1 d in vitamin A-free medium, even though squamous metaplasia was not yet obvious. Squamous tracheas were shown by immunoblot analysis to contain keratins of 50, 48, 46.5, and 45 kilodalton (kd) detected with AE1; and 58, 56, and 52 kd detected with AE3. Immunoblot analysis with monospecific antimouse keratin sera also demonstrated the presence of 60, 55, and 50 kd keratins in the metaplastic tracheas. All these various species of keratins were either absent or present in much reduced quantity in mucociliary tracheas in RAc-containing medium. Interestingly, the induction of squamous metaplasia in tracheal epithelium did not result in the expression of the 59 and 67 kd keratins which are characteristically expressed in the differentiated layers of the epidermis. Therefore, this study shows that squamous metaplasia of tracheas due to vitamin A-free cultivation is accompanied by an increase in keratin synthesis as well as by the appearance of keratin species not normally present in mucociliary tracheal epithelium.

Topics: Animals; Cricetinae; Cytoskeleton; Diterpenes; Electrophoresis, Polyacrylamide Gel; Epithelium; Fluorescent Antibody Technique; Immunologic Techniques; Immunosorbent Techniques; Keratins; Mesocricetus; Metaplasia; Organ Culture Techniques; Retinyl Esters; Trachea; Vitamin A; Vitamin A Deficiency

Topics: Animals; Epidermal Growth Factor; Female; Histocytochemistry; Immunochemistry; Keratins; Lectins; Male; Mice; Submandibular Gland; Vitamin A Deficiency

There is reported the first four members of heteroarotinoids, the names of which are ethyl (E)-p-[2-(4,4-dimethylthiochroman-6-yl)propenyl]benzoate (1b), ethyl (E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoate (1c), ethyl (E)-p-[2-(4,4-dimethyl-1-oxothiochroman-6-yl)propenyl]benzoate (1d), and (E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoic acid (1e). IR, 1H NMR and 13C NMR data have been recorded for each compound and support the structural assignments. To provide a firm basis for comparison purposes of future analogues, an X-ray analysis was performed on a single crystal of ethyl (E)-p-[2-(4,4-dimethylthiochroman-6-yl)propenyl]benzoate (1b) and a precursor 4,4-dimethylthiochroman-6-yl methyl ketone 1,1-dioxide (18). These data for the heteroarotinoid 1b revealed that the two aryl ring systems were nearly perpendicular in each of the two molecules present in the unit cell (86.37 degrees and 84.17 degrees, respectively). The space group for both molecules was P1 in triclinic systems. Unit cell dimensions (at 15 degrees C) are as follows: for 1b, a = 20.568 (6) A, b = 14.760 (3) A, c = 7.679 (2) A, alpha = 113.33 (2) degrees, beta = 79.45 (2) degrees, gamma = 79.98 (2) degrees, Z = 4; for 18, a = 9.292 (5) A, b = 9.291 (5) A, c = 7.951 (3) A, alpha = 102.16 (3) degrees, beta = 77.49 (3) degrees, gamma = 79.60 (4) degrees, Z = 2. The sulfur-containing ring is in a distorted half-chair in 1b and the methyl carbon C(12) is shown to be trans to H(13) at the C(11)-C(13) bond. The biological activity of these arotinoids was determined in the tracheal organ culture assay and compared with trans-retinoic acid for ability to reverse keratinization in vitamin A deficient hamsters. The ester 1b displayed activity about one-half log unit less than that of the reference while 1c and 1e had activity nearly one log until less than trans-retinoic acid. The sulfoxide was the least active of the heteroretinoids.

Topics: Animals; Benzopyrans; Chromans; Cricetinae; Keratins; Magnetic Resonance Spectroscopy; Models, Molecular; Organ Culture Techniques; Trachea; Vitamin A Deficiency; X-Ray Diffraction

A number of recent studies have indicated that the expression of keratins is altered upon malignant transformation of human epithelial cells. We have shown that the altered expression of 67-kDa and 40-kDa keratins in established squamous cell carcinoma lines from tongue and epidermis stems largely from a difference in their sensitivity to vitamin A apparently acquired during tumorigenesis. When the vitamin A concentration in the medium is raised, the 40-kDa keratin is produced at increased levels. Conversely, when the amount of vitamin is reduced, the 67-kDa keratin is synthesized and the cells undergo stratification and terminal differentiation. However, even when vitamin A is quantitatively removed from the medium, the maximal degree of differentiation attained by each squamous cell carcinoma cell as judged by the synthesis of 67-kDa keratin was still less than that of the normal keratinocytes. These findings suggest that the altered patterns of keratins observed for some tissues upon malignant transformation arise from a complex mixture of intracellular changes in the differentiative pathway in addition to changes in the responsiveness of cells to extracellular regulators of keratin gene expression.

Topics: Animals; Carcinoma, Squamous Cell; Carrier Proteins; Cell Differentiation; Cell Line; Diterpenes; Dose-Response Relationship, Drug; Epithelium; Fluorescent Antibody Technique; Humans; Infant, Newborn; Keratins; Male; Rabbits; Receptors, Retinoic Acid; Retinyl Esters; RNA, Messenger; Vitamin A; Vitamin A Deficiency

A series of conformationally restricted retinoids was synthesized and screened in two assays used to measure the ability of retinoids to control cell differentiation, namely, the reversal of keratinization in tracheal organ culture from vitamin A deficient hamsters and the inhibition of the induction of mouse epidermal ornithine decarboxylase by a tumor promoter. These compounds had bonds corresponding to selected bonds of the E-tetraene chain of retinoic acid (1) held in a planar cisoid conformation by inclusion in an aromatic ring. The meta-substituted analogue 3 of 4-[(E)-2-methyl-4-(2,6,6-trimethylcyclohexenyl)-1,3-butadienyl+ ++]benzoic acid (2) was far less active than 2 in both assays. In contrast, the vinyl homologue of 2 (4) and the 7,8-dihydro and 7,8-methano analogues (5 and 6) had activity comparable to that of 2. Analogues of 4-[(E)-2-(1,1,4,4-tetramethyl-1,2,3,4-tetrahydro-6-naphthyl)propenyl] benzoic acid (7) were also screened. Replacement of the tetrahydronaphthalene ring of 7 by a benzonorbornenyl group (9) significantly reduced activity, as did removal of the vinylic methyl group from 9 (10). Replacement of the propenyl group of 9 by a cyclopropane ring (12) also reduced activity. Replacement of the tetrahydronaphthalene ring of 7 by 4,4-dimethyl-3,4-dihydro-2H-1-benzopyran and -benzothiopyran rings (13 and 14) also decreased activity. Inclusion of the 7,9 double bond system of 1 in an aromatic ring (15 and 16) reduced activity, whereas inclusion of the 5,7 double bond system in an aromatic ring enhanced activity (7 and 19). Inclusion of the 11,13 and 9,11,13 double bond systems in aromatic rings (2 and 18) also reduced activity below that of 1. Retinoic acid, 7, 13, 14, and 19 inhibited papilloma tumor formation in mice. Toxicity testing indicated that 7 was more toxic than 1, 13, 14, and 19, 19 was more toxic than 1, and 13 and 14 were less toxic than 1.

Topics: Animals; Cell Differentiation; Chemical Phenomena; Chemistry; Female; Keratins; Mice; Organ Culture Techniques; Ornithine Decarboxylase Inhibitors; Papilloma; Retinoids; Skin; Structure-Activity Relationship; Trachea; Vitamin A Deficiency

Using an in vivo rabbit model system, we have studied the morphological and biochemical changes in corneal, conjunctival, and esophageal epithelia during vitamin A deficiency. Light and electron microscopy showed that the three epithelia undergo different degrees of morphological keratinization. Corneal and conjunctival epithelia became heavily keratinized, forming multiple layers of superficial, anucleated cornified cells. In contrast, esophageal epithelium underwent only minor morphological changes. To correlate morphological alterations with the expression of specific keratin molecules, we have analyzed the keratins from these epithelia by the immunoblot technique using the subfamily-specific AE1 and AE3 monoclonal antikeratin antibodies. The results indicate that during vitamin A deficiency, all three epithelia express an AE1-reactive, acidic 56.5-kd keratin and an AE3-reactive, basic 65-67-kd keratin. Furthermore, the expression of these two keratins correlated roughly with the degree of morphological keratinization. AE2 antibody (specific for the 56.5- and 65-67-kd keratins) stained keratinized corneal epithelial sections suprabasally, as in the epidermis, suggesting that these two keratins are expressed mainly during advanced stages of keratinization. These two keratins have previously been suggested to represent markers for epidermal keratinization. Our present data indicate that they can also be expressed by other stratified epithelia during vitamin A deficiency-induced keratinization, and suggest the possibility that they may play a role in the formation of the densely packed tonofilament bundles in cornified cells of keratinized tissues.

Topics: Animals; Antibodies, Monoclonal; Antigen-Antibody Complex; Conjunctiva; Cornea; Epithelial Cells; Epithelium; Esophagus; Fluorescent Antibody Technique; Keratins; Microscopy, Electron; Rabbits; Skin; Vitamin A Deficiency

Cytokinetic and ultrastructural studies were carried out to elucidate mechanisms involved in the reversal of squamous metaplasia (SM) by beta-retinoic acid in organ cultures of tracheas derived from vitamin A-deficient hamsters. Tracheal cultures exhibiting focal areas of SM were treated with the retinoid for up to 7 days. The retinoid significantly inhibited [3H]-thymidine labeling indices in the basal cells and stimulated the labeling indices in mucous cells. At the ultrastructural level the retinoid induced marked remodeling alterations in the metaplastic epithelium that included: (a) disruption of desmosomes and widening of intercellular spaces; (b) extensive vacuolation and degeneration of the metaplastic cells; (c) extrusion of the degenerated cells; (d) aggregation of keratin filaments; and (e) differentiation of certain basal cells into secretory cells. Consequently most degenerated metaplastic cells were extruded and the epithelium repopulated as a result of differentiation of basal cells into mucous cells and hyperplasia of the pre-existing mucous cells. The degenerative effects of the retinoid were limited to the metaplastic foci since the uninvolved epithelium adjoining metaplastic foci were not significantly altered. The results suggest that the restoration of normal tracheal epithelium following the retinoid treatment of explants exhibiting focal areas of squamous metaplasia is associated with the enhanced proliferation of the mucous cells. The inhibition of proliferation of basal cells further prevented hyperplasia and restored cell replication within the normal range.

Topics: Animals; Cell Differentiation; Cell Division; Cricetinae; Epithelium; Keratins; Metaplasia; Microscopy, Electron; Organ Culture Techniques; Trachea; Tretinoin; Vitamin A Deficiency

Topics: History, 20th Century; Humans; Ichthyosis; Keratins; Skin; Vitamin A Deficiency

Specific pathogen free F-344 rats were kept on a vitamin A deficient diet for 3-5 months. After 3 months on this diet the forestomach epithelium showed a mild atrophy. Stereological cytology showed a marked increase in the volume density of cytoplasmic filament bundles and decrease in the volume density of non-bundled cytoplasmic filaments. The volume fraction of keratohyalin granules increased whereas the volume fraction of membrane coating granules decreased. Some animals maintained for 4-5 months on the hypovitaminic diet exhibited the same mild atrophic forestomach epithelium accompanied by hyperkeratinization. Others showed a marked epithelial atrophy and 4 out of 12 animals revealed a marked hyperplasia with increased 3H thymidine labeling index and several papillomatous proliferations. Although many of these alterations reflect a decrease in proliferation as well as hyperkeratinization, the latter changes were not unlike those produced by known carcinogens, and support the putative important role of vitamin A in both carcinogenesis and chemoprevention.

Topics: Animals; Epithelium; Female; Hyperplasia; Keratins; Microscopy, Electron; Rats; Rats, Inbred F344; Stomach; Vitamin A Deficiency

The metabolism and bioactivity of N-(4-hydroxyphenyl)-all-trans-retinamide (HPR) and of various O-alkyl and ester derivatives of HPR were investigated in rodents. The principal metabolite of HPR in tissues is N-(4-methoxyphenyl)-all-trans-retinamide. N-(4-methoxyphenyl)all-trans-retinamide is equipotent to HPR in reversing keratinization of retinoid-deficient hamster trachea in vitro. Another nonpolar metabolite of HPR is also present in tissue and (although not positively identified) is thought to be a long-chain fatty acid ester of HPR. HPR is excreted into rat bile as numerous polar retinamides, including HPR-O-glucuronide. The rate of hydrolysis of HPR esters by rat serum and hepatic enzymes in vitro is inversely related to the length of the esterified acid side group. After a 30-min incubation at 37 degrees C in serum, percentage of hydrolysis for acetyloxy, propionyloxy, butyryloxy, pivaloyloxy and octanoyloxy esters of HPR is 41, 20, 7.5, 1.9 and 1.5, respectively. In contrast, hydrolysis by hepatic esterases is more rapid, particularly for the pivaloyloxy ester. Potency of the various HPR esters in the tracheal organ culture bioassay decreases as the length of the esterified side group increases; the acetyloxy ester is at least 5 times more potent than the octanoyloxy ester.

Topics: Animals; Biotransformation; Cricetinae; Fenretinide; Hydrolysis; In Vitro Techniques; Keratins; Liver; Male; Rats; Rats, Inbred Strains; Trachea; Tretinoin; Vitamin A Deficiency

The use of the synchronous induction method enables both assessment of the sequence and reliability of the appearance of morphologic signs of vitamin A deficiency, and their accurate correlation with biochemical and physiologic abnormalities. In the trachea, hyperplasia of basal epithelial cells was observed by Day 4 (T4) following the withdrawal of retinoic acid from retinoate-cycled, stringently deficient rats. Keratinization was observed by Day 6, the upper part of the trachea showing the highest incidence of keratinization. All such metaplastic changes originated in the narrow strip of tissue directly cojoining the esophagus. In the submaxillary glands, atrophy of the acini, an increase in interlobular spaces, and fibrosis and dilatation of the ducts was observed by Day 10. In more advanced stages of deficiency (T14-T18), cyst formation associated with suppuration and extensive cell atrophy was observed. Morphologic changes were less marked in the sublingual glands, although mucin levels were noticeably depressed by Day 12 of deficiency. Following the oral dosing of deficient animals (T12) with 350 micrograms retinyl palmitate, all such changes were reversed within 6 days in the trachea and within 10 days in the submaxillary and sublingual glands. Similar patterns were observed whether animals were force-fed or were fed ad libitum. Apart, therefore, from cause-effect considerations per se, morphologic changes are also potentially valuable reference indicators of deficiency, particularly in time course studies, or where force-feeding attenuates other signs of deficiency.

Topics: Animals; Atrophy; Keratins; Male; Metaplasia; Rats; Salivary Glands; Sublingual Gland; Submandibular Gland; Trachea; Vitamin A Deficiency

Keratinization of the tarsal conjunctiva in an eye with adequate tears occurs following a number of conditions, including irritation and sensitivity to topical medications, Stevens-Johnson syndrome, radiation to the lid, and occasionally from unknown causes. The keratinized cells produce an epithelial keratitis with subsequent vascularization of the cornea. The morphogenesis of this condition is discussed, along with therapy including mucous membrane grafts and freezing of the tissue.

Topics: Animals; Conjunctiva; Cornea; Epidermis; Eye Diseases; Eyelid Neoplasms; Humans; In Vitro Techniques; Keratins; Keratitis; Metaplasia; Stevens-Johnson Syndrome; Vitamin A Deficiency

Topics: Animals; Dietary Fats; Epithelium; History, 20th Century; Keratins; Rats; United States; Vitamin A Deficiency

Biological properties of axerophthene, the hydrocarbon analog of retinol, have been studied both in vitro and in vivo. In tracheal organ culture axerophthene reversed keratinization caused by deficiency of retinoid in the culture medium; its potency was of the same order of magnitude as that of retinyl acetate. Axerophthene supported growth in hamsters fed vitamin A-deficient diets although less effectively than did retinyl acetate. Axerophthene was considerably less toxic than was retinyl acetate when administered repeatedly in high doses to rats. Administration of an equivalent p.o. dose of axerophthene caused much less deposition of retinyl palmitate in the liver than did the same dose of retinyl acetate, while a greater level of total retinoid was found in the mammary gland after administration of axerophthene.

Topics: Animals; Body Weight; Diterpenes; Female; Keratins; Liver; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Organ Culture Techniques; Rats; Retinyl Esters; Trachea; Vitamin A; Vitamin A Deficiency

Ultimobranchial cysts in the thyroid glands of rats receiving a diet adequate in vitamin A are lined with stratified squamous epithelium and contain non-keratinized cellular debris. The epithelium of these cysts in vitamin A deficient animals is keratinized, and their lumina contain keratinized cellular strands surrounding a core of cellular debris. Upon return to a diet adequate in vitamin A the epithelium returns to a non-keratinized state, and the lumina contain keratinized strands surrounded by cell fragments and desquamated whole cells. Occasionally these cysts have an epithelium that is highly irregular in appearance. The relationship of alterations in this tissue to possible subsequent development of neoplasias is discussed.

Topics: Animals; Cysts; Cytoplasmic Granules; Desmosomes; Diet; Epithelium; Keratins; Male; Rats; Thyroid Diseases; Ultimobranchial Body; Vitamin A Deficiency

Topics: Acid Phosphatase; Animals; Cathepsins; Chediak-Higashi Syndrome; Cyclic AMP; Dermatitis; Fabry Disease; Humans; Keratins; Lupus Erythematosus, Systemic; Lysosomes; Psoriasis; Skin; Ultraviolet Rays; Vacuoles; Vitamin A Deficiency

Epithelial cells from hamster small intestine, in short term culture, incorporated [carbinol-14C]retinol into a compound that is identical to synthetic retinyl phosphate, as judged by chromatography on DEAE-cellulose, silicic acid, and thin layers of silica gel. The biological compound displays the same absorption spectrum as does synthetic retinyl phosphate with a maximum at 325 nm. Hydrolysis with mild alkali yields anhydroretinol, as it does for synthetic retinyl phosphate, with absorption maxima at 388, 368, and 346 nm. Enzymic hydrolysis by alkaline phosphatase releases 9% of the radioactivity as [14C]retinol. Under the same conditions, 9% of synthetic retinyl phosphate is hydrolyzed to retinol. The biological compound was tested for biological activity. At a concentration of 5.5 x 10-8 M it was as active as retinol and retinyl phosphate in reversing keratinization induced in hamster tracheal epithelium by vitamin A deficiency. It is concluded that hamster intestinal cells synthesize retinyl phosphate.

Topics: Alkaline Phosphatase; Animals; Cricetinae; Diterpenes; Dolichols; Epithelial Cells; Epithelium; Intestine, Small; Keratins; Male; Metaplasia; Organ Culture Techniques; Organophosphorus Compounds; Phosphates; Tracheal Diseases; Vitamin A; Vitamin A Deficiency

Keratotic and squamous changes characteristic of vitamin A deficiency were minimal even in chicks which were malnourished and growth stunted and had no vitamin A in their diet. However, when these chicks were infected with Newcastle disease virus (NDV), keratotic changes appeared, most markedly in areas regenerating after infection. In chicks raised on full nutrient diets lacking only vitamin A, keratotic changes appeared in several areas of nasal mucosa but were absent from the mucosa of the inner (under) surface of the maxillary turbinate. Following NDV infection, such changes did appear in the inner lining epithelia. It is suggested that depletion of vitamin A causes regenerating epithelial cells to keratinize. Other effects of combined lack of vitamin A plus NDV infection were exhaustion of lymphoid cells from cranial bone marrow and exhaustion of lymphoid cell systems locally from the nose and paranasal glands.

Topics: Acute Disease; Animal Nutritional Physiological Phenomena; Animals; Bone Marrow; Bone Marrow Cells; Chickens; Diet; Harderian Gland; Keratins; Newcastle Disease; Newcastle disease virus; Plasma Cells; Respiratory Tract Infections; Turbinates; Vitamin A Deficiency

Topics: Acid Phosphatase; Animals; Esterases; Histocytochemistry; Keratins; Keratosis; Male; Mouth Diseases; Mouth Mucosa; Muramidase; Rats; Sulfhydryl Compounds; Sulfides; Vitamin A Deficiency

Topics: Blood Proteins; Cell Nucleus; Cheek; Cytoplasm; Eosinophils; Humans; Keratins; Protein-Energy Malnutrition; Serum Albumin; Vitamin A Deficiency

Topics: Animals; Cell Division; Cell Nucleus; Epithelium; Keratins; Lens, Crystalline; Male; Mitosis; Rats; Rats, Inbred Strains; Vegetables; Vitamin A; Vitamin A Deficiency

Topics: Animals; Cornea; Epithelium; Keratins; Keratitis; Keratoconjunctivitis; Lacrimal Apparatus; Microscopy, Electron; Microtubules; Mitochondria; Rats; Vitamin A Deficiency; Xerophthalmia

Topics: Animals; Coloring Agents; Epithelium; Hyalin; Hyperplasia; Keratins; Mouth Mucosa; Rats; Skin; Staining and Labeling; Urinary Bladder; Vitamin A Deficiency

Topics: Animals; Atrophy; Epithelium; Inflammation; Keratins; Male; Mitosis; Parotid Gland; Rats; Salivary Glands; Sublingual Gland; Submandibular Gland; Tongue; Vitamin A Deficiency

Topics: Animals; Gingivitis; Keratins; Rats; Vitamin A; Vitamin A Deficiency

Topics: Animals; Chickens; Keratins; Metaplasia; Nasal Mucosa; Newcastle Disease; Turbinates; Vitamin A Deficiency

Topics: Animals; Cytoplasmic Granules; Epithelium; Estradiol; Keratins; Metaplasia; Methylcholanthrene; Microscopy, Electron; Rats; Urinary Bladder; Urinary Bladder Diseases; Vitamin A Deficiency

Taste preferences were studied in two groups of rats depleted of vitamin A by dietary restriction. One group received sufficient vitamin A acid supplement to maintain normal growth. The other group was repleted with vitamin A alcohol after the classical deficiency symptoms had appeared; this group gradually lost normal preferences for NaCl and aversion to quinine solutions during depletion. Vitamin A alcohol repletion tended to restore taste preferences to normal. In contrast, the group receiving vitamin A acid showed normal taste preferences throughout the depletion period. When the vitamin A acid supplement was removed taste preferences became abnormal and returned to normal when vitamin A acid was restored. Peripheral gustatory neural activity of depleted rats without any form of vitamin A was less than normal both at rest and when the tongue was stimulated with NaCl solutions. Histological examination showed keratin infiltrating the pores of the taste buds. Accessory glandular tissues were atrophied and debris filled the trenches of the papillae. It is concluded that vitamin A acid can provide the vitamin A required for normal taste, as contrasted with its inability to maintain visual function. It is suggested that the effect of vitamin A is exerted at the receptor level, as a result of its role in the biosynthesis of mucopolysaccharides, which have been recently identified in the pore area of taste buds, as well as being present in the various secretions of the oral cavity.

Topics: Acetates; Animal Nutritional Physiological Phenomena; Animals; Body Weight; Chorda Tympani Nerve; Electrophysiology; Glycosaminoglycans; Keratins; Quinine; Rats; Sodium Chloride; Sucrose; Sweetening Agents; Synaptic Transmission; Taste; Taste Buds; Tongue; Vitamin A; Vitamin A Deficiency

Topics: Animals; Epithelial Cells; Epithelium; Hyperplasia; Keratins; Keratosis; Microscopy, Electron; Rats; Urinary Bladder; Vitamin A Deficiency

Topics: Estrogens; Female; Humans; Keratins; Male; Metaplasia; Prostate; Vagina; Vitamin A Deficiency

Topics: Biliary Tract; Conjunctiva; Gallbladder Diseases; Humans; Keratins; Liver; Skin Physiological Phenomena; Vitamin A; Vitamin A Deficiency