Brysk Mm

The University of Texas Medical Branch at Galveston

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Tyring Sk

The University of Texas Health Science Center at Houston

István Arany

University of Mississippi Medical Center

Henry Brysk

The University of Texas Medical Branch at Galveston

P Selvanayagam

Madurai Medical College

Lei G

Srinivasan Rajaraman

Booz Allen Hamilton (United States)

Rassekh Ch

West Virginia University

Juanita Page

National Heart Institute

Colburn Nh

Frederick National Laboratory for Cancer Research

Calhoun Kh

Cooperative Institutions

The University of Texas Medical Branch at Galveston

Osaka University

The University of Texas Health Science Center at Houston

West Virginia University

National Heart Institute

Social Welfare Department

Institute of Art

National Institutes of Health

Frederick National Laboratory for Cancer Research

National Cancer Institute

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Gene expression of zinc-alpha 2-glycoprotein in normal human epidermal and buccal epithelia.

PubMed (1997)

Brysk Mm Lei G Srinivasan Rajaraman P Selvanayagam Rassekh Ch

Zinc-alpha 2-glycoprotein (Zn alpha 2gp) is almost ubiquitous in body fluids. We have found it to be also present in stratified epithelia. We compare its mRNA expression in cells from human epidermis and buccal mucosa cultured in media of graded differentiation potential (attained by varying calcium ion concentration and adding serum). The Zn alpha 2gp gene is upregulated in both epithelia with differentiation and further with exposure to interferon gamma or transforming growth factor beta 1. The upregulation by these agents increases with differentiation in epidermal cells, but peaks in the low-differentiation medium in buccal epithelia. We compared gene expression levels of Zn alpha 2gp with those of characteristic cytokeratins of stratified epithelia (k5 for basal cells, K10 for epidermal suprabasal cells, and K13 for mucosal suprabasal cells). This pattern correlation associates Zn alpha 2gp cell-type dependently with late differentiation, i.e. with keratin K10 in epidermis and with K13 in buccal epithelium.

Epidermis (zoology)

Alpha (finance)

Keratin 5

Ductal cells

Basal (medicine)

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Citations (13)

Response of cultured cells from the epidermis and the buccal mucosa to TGF-beta 1 and comparison to interferon-gamma.

PubMed (1996)

István Arany Tyring Sk Hoskins Sl Henry Brysk Chen Sh

Normal human cells from epidermis and from buccal mucosa were cultured to confluence in three media with graded differentiation potential (at low Ca2+, high Ca2+, and supplemented with serum) and treated with transforming growth factor beta 1 (TGF-beta 1), as had been done previously with interferon-gamma (IFN-gamma). The response of the cells to TGF-beta 1 was monitored in terms of the expression of regulatory genes associated with proliferation and differentiation (cdc2, c-myc, p53) and of genes for structural proteins expressed at varying stages of maturation (keratins K5 and K10, involucrin, flaggrin). For both tissues, the results obtained with both agents were very similar for those genes expressed in the basal cells (cdc2, c-myc, p53, K5), regardless of their function, but diverged for the other genes, which are expressed in the suprabasal cells. Another related contrast is that, although IFN-gamma induced apoptosis in epidermal keratinocytes cultured in the serum containing medium, TGF-beta 1 did not. Thus, the two agents appear to affect the earlier stages of cell differentiation in the same way but to differ at the later stages, particularly in that IFN-gamma pushes maturation further than does TGF-beta 1).

Epidermis (zoology)

BETA (programming language)

TGF beta 1

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Citations (4)

Holocaust hospital in the forests of White Russia.

PubMed (1998)

Brysk Mm

White (mutation)

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Aberrant expression of a chemokinetic glycoprotein in psoriatic skin.

PubMed (1987)

Srinivasan Rajaraman Schmalsteig Fc Brysk Mm Hendrick Sj Solomon Ar

Clinically involved and uninvolved skin samples of 6 psoriatic patients, 4 samples each of normal skin specimens, basal cell carcinoma and keratoacanthoma were studied by an indirect immunofluorescence technique. The monospecific antibody used in this study was directed against a 30 kD glycoprotein, normally expressed by the terminally differentiated corneocytes. Functional characterization of this glycoprotein was evaluated by neutrophil cell movement assays. The involved and uninvolved skin of psoriatic patients expressed the 30 kD glycoprotein not only in the stratum corneum but in all the viable epidermal layers as well. Functional studies revealed this glycoprotein to be a potent chemokinetic molecule. These results suggest that the 30 kD glycoprotein is an intrinsic chemokinetic molecule of the terminally differentiated corneocytes, and its precocious and aberrant expression in psoriatic epidermis is potentially responsible for some of the pathophysiologic aspects of psoriasis.

Corneocyte

Epidermis (zoology)

Keratoacanthoma

Immunofluorescence

Pathophysiology

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Differentiation and IFN gamma regulate WAF1/CIP1 transcription in p53-independent and p53-dependent pathways in epithelial cells.

PubMed (1996)

István Arany Brysk Mm Calhoun Kh Tyring Sk

In normal epithelia differentiation and proliferation are regulated by factors involving p53 and related pathways. WAF1/CIP1 protein is believed to inhibit cell growth as a downstream mediator of p53 function. Also, WAF1/CIP1 is identified as a candidate gene linking differentiation signals to G1 arrest. Different epithelia with different keratinizing profiles respond differently to differentiation/proliferation signals, such as calcium or interferon gamma (IFNgamma). Other factors, such as p53 mutation or presence of human papillomaviruses (HPVs) also affect responses to those signals. Since WAF1/CIP1 can be regulated via a p53-dependent or an independent manner, our study aimed to determine: a.) differentiation-related expression of WAF1/CIP1 in keratinocytes, b.) involvement of WAF1/CIP1 in IFNgamma action, and c.) p53-dependence of WAF1/CIP1 transcription under these conditions. The results demonstrated that differentiation increases WAF1/CIP1 transcription in keratinizing but not in nonkeratinizing keratinocytes in a p53-independent manner. IFNgamma upregulated WAF1/CIP1 in keratinizing keratinocytes in a differentiation and p53 dependent manner. Inactivation of wild type p53 by mutation or by presence of HPVs uncouples IFNgamma-mediated WAF1/CIP1 transcription from p53 and from differentiation. Our data suggest a mechanism which operates via WAF1/CIP1 in keratinocytes and regulates epithelial differentiation/proliferation under different physiological conditions.

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Discrimination between nonmalignant and malignant cells by combinations of IFN-gamma and IFN-alpha/beta.

PubMed (1984)

Fleischmann Wr Newton Rc Fleischmann Cm Colburn Nh Brysk Mm

Combination treatment with interferon (IFN)-gamma and either IFN-alpha or IFN-beta synergistically enhances (potentiates) the anticellular effects of the IFNs. IFNs have been shown to have anticellular activity against normal as well as malignant cells. To study the relative effectiveness of IFN's anticellular activity against nonmalignant and malignant cells in the mouse system, two paired sets of nonmalignant/malignant cells (JB-1/JB-8; D-1/D-11a) were studied using 3-day kinetics of cell growth experiments. Treatment of the nonmalignant cells with IFN-gamma or IFN-alpha/beta employed separately had little or no effect on the growth of the cells at the IFN concentrations employed. Combination IFN treatment had only a slight effect on the growth of these cells. Treatment of the malignant cells with IFN-gamma or IFN-alpha/beta employed separately had low levels of effect on the growth of the cells. In contrast, treatment of these malignant cells with combined IFN-gamma and IFN-alpha/beta had a very marked anticellular effect, dramatically showing the growth of, or even killing, the malignant cells. These observations appeared to be independent of the growth status of the cells, since stationary-phase and log-phase malignant cells maintained their relatively greater sensitivity to the IFNs. Thus, IFN treatment, particularly combination IFN treatment, had a differential effect on the growth of the paired sets of nonmalignant and malignant cells and appeared to sharply differentiate between nonmalignant and malignant cells.

Malignant cells

BETA (programming language)

Alpha (finance)

Growth inhibition

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Citations (13)

Proteasomal RNase activity in human epidermis.

PubMed (1998)

T. Horikoshi Juanita Page Lei G Henry Brysk István Arany

The proteasome is a cytoplasmic high-molecular-weight structure composed of several smaller protein and RNA subunits. It has been associated with non-lysosomal pathways of intracellular degradation, expressing multicatalytic proteinase activities and specific RNase activity. By standard methods, we have isolated andpartially purified proteasomes from human epidermis. We obtained the expected multiple 24-32 kDa subunits by SDS-PAGE, and evidence of RNA. Proteasomes degraded casein, as well as chromogens for t-PA and trypsin but not for chymotrypsin, these proteolytic activities overlap, but do not coincide with those observed in other organs. We found that human epidermal 28 S and 18 S rRNAs were degraded, but yeast RNA was not. By means of zymography, we demonstrated, for the first time, that RNase activity persists after dissociation of the proteasome on the gel and that it co-localizes to the same range of molecular weight subunits as the proteinase activity.

RNase MRP

Epidermis (zoology)

Proteolysis

Zymography

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Citations (5)

Modulation by interferon-gamma of zinc-alpha 2-glycoprotein gene expression in human epithelial cell lines.

PubMed (1997)

Brysk Mm Lei G P Selvanayagam Henry Brysk Tyring Sk

Zinc-alpha 2-glycoprotein has been detected in most body fluids, and its antibody labels the corresponding glandular epithelia. We have also detected it in human stratified epithelia (epidermis and buccal mucosa). In this study, the mRNA levels of zinc-alpha 2-glycoprotein were found to be about twice as high in epithelial cells of mucosal origin (whether normal primaries or neoplastic cell lines) as in epidermoid cells (normal epidermal primary cultures, an immortalized but non-tumorigenic epidermal cell line, and neoplastic vulvar and cervical cell lines). Interferon-gamma strongly upregulated gene expression, but substantially less in mucosal than epidermoid cells. To compare responses as a clue to the function of zinc-alpha 2-glycoprotein, we ran parallel experiments with three markers of distinct properties, all known to be induced by interferon-gamma. There was the least resemblance for involucrin, a qualitative similarity for HLA-DR, and a rather better match for 2'-5' oligoadenylate synthetase.

Epidermoid carcinoma

Epidermis (zoology)

Alpha (finance)

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Citations (7)