Biomedical subjects

K Sellheyer

Publications and source records attributed to K Sellheyer.

17 recordsLinked to original sources

PubMed2001

Distribution of Bcl-2 and Bax in embryonic and fetal human skin: antiapoptotic and proapoptotic proteins are differentially expressed in developing skin.

The Bcl-2 protein is involved in the regulation of apoptosis. Bax has an antagonistic effect and enhances cell death. We report that in early gestation, Bcl-2 and Bax colocalize to the epidermal portion of the hair follicle. In the more advanced stages, Bax is located in the compartments where a hair canal is excavated and keratinization and holocrine secretion are initiated, in contrast to Bcl-2, which is expressed in the follicular papilla, preventing apoptosis and underscoring its role as a permanent and stable population of specialized fibroblasts. Scattered dendritic cells located in the basal and immediate suprabasal interfollicular epidermis as well as in the outer root sheath of the developing hair follicle, including the bulge, strongly express Bcl-2 and label for HMB-45, identifying them as melanocytes. The spatial and temporal expression pattern of Bcl-2 and Bax during human hair follicle development underscores their importance for hair biology and most likely is disturbed in the evolution of follicular tumors.

Apoptosis↗

PubMed1995

Multiple defects and perinatal death in mice deficient in follistatin.

Follistatin, an activin-binding protein and activin antagonist in vitro, can bind to heparan sulphate proteoglycans and may function in vivo to present activins to their receptors. In the mouse, follistatin messenger RNA is first detected in the deciduum (on embryonic day 5.5), and later in the developing hindbrain, somites, vibrissae, teeth, epidermis and muscle. In Xenopus laevis, overexpression of follistatin leads to induction of neural tissue. Here we use loss-of-function mutant mice to investigate the function of follistatin in mammals. We find that follistatin-deficient mice are retarded in their growth, have decreased mass of the diaphragm and intercostal muscles, shiny taut skin, skeletal defects of the hard palate and the thirteenth pair of ribs, their whisker and tooth development is abnormal, they fail to breathe, and die within hours of birth. These defects are more widespread than those seen in activin-deficient mutant mice, indicating that follistatin may modulate the actions of several members of the transforming growth factor-beta family.

Animals↗

PubMed1995

[Transgenic mice as models for skin diseases].

Naturally occurring animal models are not available even for most common skin diseases. Transgenic technology developed during the 1980s is closing this gap. It was initially used as a tool by scientists in basic research, but during the last 5 years it has increasingly been applied by clinically oriented basic researchers in dermatology. This technique, has made it possible to imitate HIV-associated diseases and genodermatoses in the murine model and to elucidate their pathogenesis. Owing to specifically induced epidermally localized overexpression of growth factors and cytokines, the skin of transgenic mice exhibited similarities to those of the psoriatic epidermis. Such animals are also useful for studying wound healing. Furthermore, transgenic technology enables us to induce cutaneous tumors selectively. The availability of animal models for human skin diseases is also of value in elucidating experimental therapeutic approaches, e.g., the somatic gene therapy.

Animals↗

PubMed1993

Inhibition of skin development by overexpression of transforming growth factor beta 1 in the epidermis of transgenic mice.

To assess the effect of transforming growth factor beta 1 on the skin in vivo, we have targeted its expression to the epidermis of transgenic mice. To ensure that active TGF-beta 1 was expressed, we used a porcine TGF-beta 1 cDNA with mutations of Cys-223-->Ser and Cys-225-->Ser, which allow constitutive activation. Mice expressing the mutant transforming growth factor beta 1 transgene exhibited a marked phenotype at birth. The skin was very shiny and tautly stretched. These animals were rigid and appeared to be restricted in their ability to move and breathe; death occurred within 24 hr. Histologically, the most prominent features of the skin were a compact orthohyperkeratosis and a reduction in the number of hair follicles. Pulse-labeling studies with 5-bromodeoxyuridine demonstrated a marked reduction in the number of replicating cells in the epidermis and hair follicles. Thus, the macro- and microscopic appearance of these mice, as well as their neonatal lethality, most likely result from inhibition of normal skin development and suppression of epithelial cell proliferation by the overexpression of transforming growth factor beta 1.

Amino Acid Sequence↗

PubMed1993

Transgenic models of skin diseases.

BACKGROUND: Transgenic animals have greatly enhanced our understanding of the contribution of various structural and regulatory components to epidermal biology. The expression of mutant versions of these components in the epidermis of transgenic mice has generated animal models of specific human skin diseases. OBSERVATIONS: The expression of mutant keratin genes has produced animal models of epidermolysis bullosa simplex and epidermolytic hyperkeratosis and, in doing so, has focused attention on the genetics of keratins in these and other skin disorders. Similarly, the generation of mice overexpressing growth factors and/or oncogenes, exclusively in the epidermis, has identified the role of these factors in normal skin and produced models of disease states where the regulation of these factors is perturbed. CONCLUSIONS: These models of keratin disorders and other diseases not only enable the determination of the cause of these disorders, but also allow evaluation of novel therapeutic techniques for the amelioration of these skin diseases.

Animals↗

PubMed1993

Targeted overexpression of transforming growth factor alpha in the epidermis of transgenic mice elicits hyperplasia, hyperkeratosis, and spontaneous, squamous papillomas.

To assess the effects of transforming growth factor alpha (TGF-alpha) on mammalian skin in vivo, we have targeted its expression to the epidermis of transgenic mice using a vector based on the human K1 (HK1) gene. Neonatal mice expressing the HK1.TGF-alpha transgene were often smaller than normal littermates and had precocious eyelid opening and wrinkled, scaly skin with diffuse alopecia. Juvenile transgenic mouse epidermis was uniformly hyperkeratotic, but this pattern was generally less pronounced in adult transgenic mice unless they expressed high levels of the HK1.TGF-alpha transgene. Spontaneous, squamous papillomas occurred at sites of wounding in adult mice expressing high levels of HK1.TGF-alpha; however, most were prone to regression. Immunoreactive TGF-alpha was 2-6 times higher in the epidermis of these HK1.TGF-alpha lines. Immunoreactive epidermal growth factor receptor had a normal pattern of expression in nonphenotypic adult epidermis, but a marked reduction in the receptor population was detected in hyperplastic newborn epidermis and phenotypic adult epidermis. Autoradiographic localization of 125I-epidermal growth factor showed a similar pattern of distribution, suggesting that the sites of increased TGF-alpha expression induced epidermal growth factor receptor down-regulation. These data demonstrate the in vivo effect of deregulated TGF-alpha expression on epidermal proliferation and differentiation and suggest a potential role for TGF-alpha in carcinogenesis and other hyperproliferative epidermal disorders.

Animals↗

PubMed1990

Development of the choroid and related structures.

The development of the choriocapillaris and the choroid is described using light and electron microscopy. Up to the seventh week after conception, the endothelium of the choriocapillaris is thick and contains many cytoplasmic vesicles. By the ninth week the endothelium flattens and becomes vesiculated. Fenestrations are found as early as the seventh week, whereas the continuous basement membrane is only observed at the ninth week. The first choroidal arterioles and venules can be seen during the fifteenth week and the arteries and veins become distinguishable at the twenty-second week. Haller's and Sattler's layers are both venous and arterial at the time of their first appearance.

Choroid↗

PubMed1989

Isolation and antigenic profile of follicular dendritic cells.

Follicular dendritic cells (FDC) were isolated from human tonsils and adenoids. With a simple modification of an isolation method described previously, FDC could be enriched up to 50%. The isolated FDC were characterized immunocytochemically. In contrast to previous studies, CD4 antigen was not detected on freed FDC, thereby suggesting that the CD4 molecule does not play a role in the infection process of FDC in AIDS, as has been demonstrated for T helper cells. Fc receptors could not be found on FDC by the panel of monoclonal antibodies applied, whereas C3 receptors were observed in abundance. Therefore, antigen trapping in germinal centres most probably involves only C3 receptors. This concept is in contrast with the current one (also developed on isolated cells), which postulates the involvement of Fc receptors. The extent to which C3 receptors are involved in the pathogenesis of AIDS will be examined in further studies.

Adenoids↗

PubMed1989

[Light and electron microscopy studies of the development of the human ciliary body].

In human embryos and fetuses with a gestation age of 9.5 to 24 weeks, differentiation of the ciliary muscle was examined by both light and transmission electron microscopy, and the surface morphology of the ciliary body was analyzed by scanning electron microscopy. Smooth muscle cells develop from mesenchymal elements or early fibroblasts located at the anterior rim of the optic cup. Musclelike cells exhibiting dense bodies and myofilaments were first distinguished during week 12 and smooth muscle cells with an adultlike appearance become apparent during week 15/16. A cellular maturation process can be observed up to week 22. Fibroblasts separating the muscle cell layers from each other also derive from the same precursor cells, as do smooth muscle cells, thereby pointing out the close relationship between the two cell types. The first radial ciliary folds could be observed at week 10.3 by scanning electron microscopy. However, true ciliary processes have only been described at week 24. The ciliary processes observed during week 24 only differed from those of the adult eye by the dimensions and lack of surface infoldings. A primitive pars plana was first identified during week 24. The morphological basis for aqueous humor production is discussed.

Ciliary Body↗

PubMed1988

Morphology of the developing choroidal vasculature in the human fetus.

In human fetuses with a gestation age of 12 to 22 weeks, the development of Haller's and Sattler's choroidal vascular layer was examined by both light and transmission electron microscopy. Even during week 12 arterioles could be identified. However, during this week they were only found in close association to the entrance of the optic nerve. Beginning with week 15/16, arterioles were also located outwards to the choriocapillary layer more anteriorly. When the arterioles first appeared, they exhibited the same ultrastructural features as those described in adults. Arteries first became apparent during week 22. They had not developed a complete internal elastic lamina. In contrast to those of the adult eye, smooth muscle cells of the fetal choroidal arteries exhibit glycogen granules. Haller's and Sattler's layer are both arterial and venous in nature.

Arteries↗

PubMed1988

Surface differentiation of the human corneal epithelium during prenatal development.

Using scanning and transmission electron microscopy, differentiation of the anterior surface of the corneal epithelium was studied in human embryos and fetuses with a gestation age from 6.4 to 22 weeks. Up to week 6/7 microvilli/microplicae are not often found; they arise in larger amounts beginning in week 7. During week 22, the morphological appearance of the corneal surface is almost adultlike. Antennulae microvillares and microfilaments running axially in microvilli can be found beginning with week 16/17.

Cornea↗

PubMed1988

Ultrastructural observations on the development of the human conjunctival epithelium.

In human embryos with a gestation age of 8.6-22 weeks, the palpebral conjunctival epithelium was examined by transmission electron microscopy (TEM). During the gestation period studied, the structural integrity of the tissue is established by an increase in the quantity of tonofilaments, desmosomes, and hemidesmosomes as well as by the undulating appearance of the cell membranes, the widening of the intercellular space, and the development of cytoplasmic protrusions into it. The superficial cells display a chronological sequence in the elaboration of transport mechanisms. A precursor stage is described for hemidesmosome formation at the interface between the basal cell membrane and the conjunctival stroma.

Conjunctiva↗

PubMed1988

The fine structure of the developing human choriocapillaris during the first trimester.

In human embryos with a gestational age ranging from 6.5 to 13 weeks the development of the choriocapillaris was studied by electron microscopy. A continuous maturation process was observed over the whole period, which was most pronounced between weeks 6.5 and 9.7. During the earlier weeks, the endothelium appeared to be rather thick and contained many cytoplasmic vesicles; it was markedly flattened and less vesiculated than at week 9.7. This process was accompanied by an enlargement in the vascular lumina. Fenestrations directed towards the primitive Bruch's layer were found to be already present at week 7.2 but increased in number from week 9.7 to week 13. In the early weeks, basement membrane structures were present in small, discontinuous tufts of cloudy material adjacent to the endothelium. These structures became continuous at week 9.7 and increased in thickness towards week 13. In the earlier weeks, punctate junctions were seen. Beginning with week 9.7, adultlike tight junctions between the endothelial cells became observable. Pericytes were already present at week 6.5. It is suggested that both pericytes and endothelial cells are derived from the differentiating mesenchymal cells of the surrounding ocular stroma.

Basement Membrane↗

PubMed1988

Surface morphology of the human ciliary body during prenatal development. A scanning electron microscopic study.

The development of the ciliary body was examined by scanning electron microscopy in human embryos and fetuses with a gestation age of 9.5 to 24 weeks. During this period it was possible to follow up the main morphogenetical events, beginning with the appearance of the first radial folds up to the occurrence of ciliary processes with a rather adultlike arrangement. The ciliary processes observed during week 24 differed from those of the adult eye only by their dimensions and the lack of surface infoldings. A primitive pars plana could only be identified during week 24. The morphological basis for aqueous humor production is discussed.

Ciliary Body↗

PubMed1988

Development of the human sclera. A morphological study.

Differentiation of the sclera in human embryos and fetuses with a gestation age from 6.4 to 24.0 weeks was studied by light and electron microscopy. The developmental route was found to be anteroposterior and directed from inside outwards. Continuous cytological maturation begins anteriorly during week 7.2 with a loss of free ribosomes and polysomes and an increase in the amount of rough-surfaced endoplasmic reticulum (rER) and Golgi complex components. From the region of the future limbus, these cytodevelopmental events progress posteriorly. By week 13 there are no marked differences between anterior and posterior localization. The cytodevelopmental events directed from inside outwards were found to begin during week 7.2, with a marked increase in the addition of glycogen and lipid droplets in the choroidal half of the anterior scleral condensation and from there progressing to the outer (episcleral) half. With the beginning of week 10.9 no more differences were identified between the outer and the inner portions of the sclera. Portions of the ER denuded of ribosomes close to the plasmalemma were observed during the whole gestational period studied. The role of these structures and the involvement of the Golgi complex for the biosynthesis of collagen are discussed. In week 24, the diameter of the collagen fibrils had increased more than three times in comparison with week 6.4. Elastic microfibrils were found beginning with week 7.2, whereas the elastic deposits with central electron-translucent cores were characterized for the first time beginning with week 18.

Collagen↗

PubMed1988

Differentiation of the ciliary muscle in the human embryo and fetus.

In human embryos and fetuses with a gestation age of 10.3 to 22 weeks, differentiation of the ciliary muscle was examined both by light and transmission electron microscopy. The smooth muscle cells develop from mesenchymal elements or early fibroblasts located in the region between the anterior scleral condensation and the ciliary pigment epithelium. The first musclelike cells exhibiting myofilaments and dense bodies could be distinguished during week 12. Smooth muscle cells with an adultlike appearance become apparent during week 15/16. Up to week 22, a cellular maturation process can be observed. Fibroblasts separating the muscle cell layers from each other also derive from the same precursor cells, as do the smooth muscle cells, thereby pointing to the close relationship between the two cell types.

Ciliary Body↗

PubMed1987

Ultrastructure of the human posterior tunica vasculosa lentis during early gestation.

In human embryos with a gestational age of from 7.6 to 14.0/15.0 weeks, the posterior tunica vasculosa lentis (TVL) was examined by both scanning and transmission electron microscopy. Even at the very early age of 7.6 weeks the tunica was found to be fully developed. It consisted of a radiating network of tortuous capillaries. Their walls were composed of a continuous layer of endothelial cells, surrounded by a basement membrane and a discontinuous sheath of pericytes. The thickness of the basement membrane increased with increasing gestational age. As opposed to previous studies, the endothelial cells exhibited transitory fenestrations. In the neighborhood of the posterior TVL macrophages were found.

Blood Vessels↗