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Biomedical subjects

R Paus

Publications and source records attributed to R Paus.

174 records · Page 10Linked to original sources
PubMed1990

Epithelial growth by rat vibrissae follicles in vitro requires mesenchymal contact via native extracellular matrix.

An in vitro assay utilizing the rat vibrissa anagen follicle as a model for studying the epithelial-mesenchymal interactions (EMI) in hair growth is described. Through selective disruption of the epithelial-mesenchymal interface, we investigate whether the specialized extracellular matrix (ECM) of the dermal papilla and basement membrane zone (BMZ) serves a crucial function in hair follicle EMI. Epithelial bulbs incubated intact within their follicular sheaths incorporate thymidine primarily into cells of the hair matrix and outer root sheath, as shown by autoradiography. However, after removal of its mesenchymal associations (dermal papilla and extrabulbar connective tissue), the epithelial bulb showed no incorporation. Neither externally added collagen (type I or IV) nor the basement membrane components in Matrigel could substitute for the growth supporting influence of native surrounding stroma. Mechanical separation of the bulb from the dermal papilla in the basement membrane zone inhibited thymidine incorporation by the epithelium even though mesenchyme was still in close proximity. Enzymatic digestion of the dermal papilla ECM and the basal lamina by Dispase, a fibronectinase and type IV collagenase, also inhibited bulb growth without evidence of cytotoxicity. These experiments suggest that direct epithelial to mesenchymal contact is required for the support of follicular epithelial growth in vitro and that specific ECM components, possibly fibronectin and/or type IV collagen, rather than diffusable factors alone, play a crucial role in the mechanism of hair follicle EMI. The in vitro system described here provides an alternative to developmental EMI models and may serve as a valuable tool for studying EMI in the adult mammalian organism.

Animals↗
PubMed1990

Telogen skin contains an inhibitor of hair growth.

We have investigated whether C57B1-6 mouse skin with all its follicles in the telogen stage of the hair cycle contains a hair-growth inhibitory activity, as opposed to skin with anagen follicles. Crude aqueous extracts of whole telogen mouse skin (TE), anagen skin (AE) or vehicle alone (V) were injected intraperitoneally into mice in which anagen had previously been induced by plucking of telogen hair follicles. Injection of TE, but not AE or V, significantly retarded the development of anagen follicles, as measured by macroscopic and quantitative microscopic hair growth parameters (skin pigmentation and thickness, appearance of trichohyaline granules) and the incorporation of tritiated thymidine into mouse skin from animals previously treated with either TE or V (skin organ culture). This inhibitory activity seemed to be localized to the epidermis and was also present in rat epidermis. We suggest that this apparently non-species-specific inhibitor present in telogen skin may play a role in regulating the hair cycle in rodents.

Animals↗
PubMed1989

Hypothesis: possible role for the melatonin receptor in vitiligo: discussion paper.

A new unifying hypothesis for the aetiology of vitiligo is proposed, in which we postulate that the final destruction of melanocytes in vitiligo results from a cascade of reactions initiated by a disregulation of melanogenesis, caused by activation of the melatonin receptor. These events result in the high and uncontrolled production of free radicals and toxic products of melanogenesis which sequentially damage or destroy melanocytes and keratinocytes, provoke an autoimmune response against exposed intracellular or altered cell surface antigens, and increase the propensity of melanocytes to undergo malignant transformation.

Humans↗
PubMed1989

The induction of anagen hair growth in telogen mouse skin by cyclosporine A administration.

One clinical complication of immunosuppressive cyclosporine A (CsA) therapy is the stimulation of hair growth. Since few pharmacologic agents cause hypertrichosis, CsA appears particularly interesting for investigating the mechanisms which control normal hair formation. Previous investigators have shown that CsA affects the hair growth of the laboratory rat, several genetic variants of mice, as well as humans, and they have concluded that CsA influences keratinization predominantly. Using a well-defined in vivo assay which measures the induction of hair follicle growth, we report here that CsA induces resting (telogen) follicles to enter active growth (anagen) in normal laboratory mice (C57 B1-6), i.e., animals with a normal hair cycle. The experiments indicate that the rate of anagen induction is dependent on the dose, time course, and method of administration and that it may be mediated via a direct action of CsA on the skin and its appendages. These studies suggest that understanding the molecular mechanisms of CsA action on hair growth will help elucidate the mechanisms of normal anagen induction.

Administration, Topical↗
PubMedDate not supplied

The psoriatic epidermal lesion and anagen hair growth may share the same "switch-on" mechanism.

Based on striking parallels between the cell kinetics in the epidermal lesion of psoriasis and the proliferation of hair matrix keratinocytes during the anagen phase of the hair growth cycle, the hypothesis is proposed that both phenomena may share the same "switch-on" mechanism. Particular emphasis is placed on a comparison between the Koebner phenomenon in psoriasis and wounding-induced anagen hair growth. In discussing alternative theoretical models for the proposed common "switch-on" mechanism, some useful experimental tools are suggested. Research into the mechanisms which control epithelial proliferation in psoriasis and hair growth may provide new insights into other growth processes, such as embryonic organogenesis and neoplasia, in which similar epithelial-mesenchymal interactions play a pivotal role.

Animals↗
PubMedDate not supplied

Beta-adrenergic receptors in nasal tissue with reference to their role in asthma and atopy.

Thirty-three samples of nasal tissue (turbinates and polyps) were collected and assayed for beta-adrenergic receptor (BAR) sites (radio-ligand assay). Patients were divided into groups: 1) nasal turbinates, 2) nasal polyps, both under the aspects of atopy and bronchial hyperreactivity. Different radiobinding was found in both groups: Patients A with high BAR and patients B with low BAR numbers. There was no correlation between BAR numbers--clinical symptoms and bronchial hyperreactivity. Generally the BAR numbers were higher in turbinates (p less than 0.01) than in polyps and in nonatopic compared to atopic patients (p less than 0.005). "Affinity state 1" BAR are equal in all groups; however, "affinity state 2"BAR are significantly less in polyps (p less than 0.05). In 50% of the examined cases there was a combination of polyps, asthma and atopy putting foreward a common line of pathogenesis in this entity. It is discussed that the underlying inflammation (allergic and non-allergic) is the cause for reduced BAR numbers in the effected tissue. So far nasal tissue seems to be like a mirror compared to the results from lower respiratory tract tissue with respect to beta-adrenergic receptors.

Animals↗
PubMedDate not supplied

Is alopecia areata an autoimmune-response against melanogenesis-related proteins, exposed by abnormal MHC class I expression in the anagen hair bulb?

The etiology of alopecia areata (AA), a putative autoimmune disease characterized by sudden hair loss, has remained obscure. It is not understood, how the characteristic inflammatory infiltrate that selectively attacks anagen hair follicles in AA is generated. We hypothesize that this reflects an unexplored form of autoimmunity, a cytotoxic T cell attack on rhythmically synthesized autoantigens normally sequestered by a lack or very low level of MHC class I (MHC I)-expression, and suggest the following mechanism of AA pathogenesis: Microtrauma, neurogenic inflammation, or microbial antigens cause a localized breakdown of MHC I-"negativity" in the proximal anagen hair bulb via proinflammatory cytokines. This exposes autoantigens derived from melanogenesis-related proteins (MRP-DP), which are only generated during anagen, and triggers two successive waves of autoimmune responses: CD8+ cytotoxic T cells initiate AA after recognizing MRP-DP abnormally presented by MHC I molecules on hair matrix melanocytes and/or keratinocytes; a secondary attack, carried by CD4+ T cells and antigen presenting cells, is then mounted against MHC class II--presented additional autoantigens exposed by damaged melanocytes and keratinocytes. The latter causes most of the follicular damage, and extrafollicular disease, and depends greatly on the immunogenetic background of affected individuals. This unifying hypothesis explains the clinical heterogeneity and all salient features of AA, and argues that only the unlikely coincidence of multiple predisposing events triggers AA. The suppression of MHC I--expression and synthesis of MRP in the hair bulb, and the "tolerization" of MRP-DP autoreactive CD8+ T cells may be promising strategies for treating AA.

Alopecia Areata↗
PubMedDate not supplied

Elements of the interleukin-1 signaling system show hair cycle-dependent gene expression in murine skin.

Stringently controlled changes in the local, cytokine-mediated signaling milieu of hair follicles (HF) have been implicated as major elements of hair cycle control and several lines of clinical and experimental evidence point towards interleukin-1 (IL-1) as an important inducer of hair loss. To address the question as to whether the steady state mRNA levels of the gene expression of the IL-1 family parallel distinct phases of the murine hair cycle, we have exploited the high degree of synchrony during depilation-induced HF cycling in mice, and have determined the mRNA levels of IL-1alpha, IL-1beta, IL-1-receptor antagonist, IL-1 receptor (R)-I and IL-1-R-II by semiquantitative RT-PCR. Our results indicate that the induced murine hair cycle is associated with profound fluctuations in the steady state mRNA levels of members of the IL-1 signaling system. Most interestingly, IL-1alpha and IL-1beta transcript levels increased dramatically with the onset of spontaneous catagen (around day 18) and peaked during telogen (day 25). These fluctuations in the IL-1alpha and IL-1beta transcript levels were paralleled by substantial expression changes of the corresponding signal transducing type I IL-1 receptor. Therefore, our findings are consistent with the concept that IL-1alpha, IL-1beta, IL-1-RI and IL-1-RII are involved in the control of catagen development.

Animals↗
PubMedDate not supplied

Inhibition of melanogenesis as an adjuvant strategy in the treatment of melanotic melanomas: selective review and hypothesis.

Melanogenesis generates immunosuppressive and mutagenic environment and alters cellular metabolism. Melanin can protect malignant melanocytes against chemo-, radio-, and photodynamic therapy. Therefore, we propose to inhibit melanogenesis as an adjuvant treatment modality during immuno-, radio-, chemo- and photodynamic therapy, and as a measure of reducing the probability of melanoma progression.

Antimetabolites, Antineoplastic↗