Biomedical subjects

I A Bernstein

Publications and source records attributed to I A Bernstein.

At least 19 recordsLinked to original sources

PubMed2002

An ergonomic comparison of rowing machine designs: possible implications for safety.

OBJECTIVES: Ergometer training is a common cause of injuries in rowers. A randomised crossover study comparing two power head designs was carried out to examine ergonomic risk factors. METHODS: Six elite male rowers undertook 20 minute fatiguing rowing pieces with both fixed and floating power heads. A CODA MPX infrared telemetric motion analysis detector and the ergometer's interface were used to measure displacement, force, work performed, and power output. RESULTS: There was no significant difference in the total work performed, power per stroke, or metabolic load between the two ergometer designs. Fatigue was shown by a mean (SEM) fall of 9.7 (0.79) W/stroke (95% confidence interval (CI) 8.0 to 11.5) between minutes 8-10 and minutes 16-18 (p<0.001). The stroke length was 53 (13) mm (95% CI 18 to 89) longer with the fixed power head (p<0.02). With fatigue, the stroke with the fixed power head lengthened at the "catch" (beginning of the stroke) by 19.5 mm (p<0.01) and shortened at the finish of the stroke by 7.2 mm (p<0.05). No significant changes in stroke length were seen with the floating power head. The mean force per stroke was 12.1% (95% CI 3.0 to 21.2) (27.3 (8.0) N) higher with the power head fixed versus floating (p<0.02). CONCLUSIONS: It is postulated that longer stroke lengths and greater forces are risk factors for soft tissue injuries. Further research into whether floating power head rowing ergometers are associated with lower injury rates than fixed power head designs is now needed.

Adult↗

PubMed1999

DNA repair in primary human keratinocyte cultures after low level exposure to bis(2-chloroethyl)sulfide.

The literature has reported the appearance and disappearance of single-strand breaks (SSBs) in the DNA of rat keratinocytes after exposure to low levels of bis(2-chloroethyl) sulfide (BCES). Since SSBs are a consequence of depurination or depyrimidination followed by excision of the apurinic or apyrimidinic site and deoxyguanosine (GdR) is the major alkylation site in DNA exposed to BCES, it was hypothesized that repair occurred by a GdR-specific base replacement and not by large section repair. To test this hypothesis, cultures of human keratinocytes (HK) were preincubated with 5-bromo-2'-deoxyuridine (BUdR), a heavy analog of thymidine (TdR) incorporated into replicating DNA, immediately before exposure to BCES. Cultures were incubated postexposure with BUdR, radiolabeled GdR, and/or deoxyadenosine (AdR), to measure base-specific repair, and/or radiolabeled TdR, to measure DNA replication and large section repair. A CsCl density gradient was used to remove any BUdR-containing postexposure DNA replication. Each gradient was assayed for radioactivity (cpm) and DNA content (absorbance at 260 nm). The peak A260 fractions were pooled and rebanded in another CsCl gradient. If DNA repair had occurred, the specific activity (cpm/A260) of the peak A260 fraction in the gradient would be greater than control. After exposure of the cultures to BCES, there was a concentration-dependent increase in the specific activity for [3H]GdR but not [4C]TdR over the concentration range used (20-50 microM BCES). A concentration-dependent increase in specific activity was also detected after [14C]AdR exposure. The literature has also reported that the removal of damaged DNA bases after alkylation is via glycosylases. In this series of experiments, we have demonstrated that cultures of HK exposed to the alkylating agent BCES repair their damaged DNA by the replacement of the damaged base only. In the case of BCES exposure, it is the GdR base and to a lesser extent the AdR base.

Carcinogens↗

PubMed1996

Formation of interstrand DNA cross-links by bis-(2-chloroethyl)sulfide (BCES): a possible cytotoxic mechanism in rat keratinocytes.

Interstrand cross-links in the DNA of epidermal basal keratinocytes may be responsible for cell death and consequent vesication in skin exposed to BCES. The formation of cross-links and cytotoxicity were compared when cells in primary monolayer cultures of rat epidermal keratinocytes, synchronized at the G1/S boundary or in the G1 phase of the cell cycle, were exposed to BCES. The dose-responsive formation of cross-links, measured with an ethidium bromide-fluorescence assay, was determined immediately after exposure of cells at either position of the cycle. At 24 hr post-exposure, the level of cross-links in cells exposed at the G1 phase showed had not decreased significantly and was still dose-dependent. However, cells exposed in the G1 phase showed a major decrease in cross-links. Formation of interstrand DNA cross-links appears to be related to the mustard's cytotoxicity.

Animals↗

PubMed1996

Bis(2-chloroethyl)sulfide (BCES) disturbs the progression of rat keratinocytes through the cell cycle.

Epidermal basal keratinocytes are the primary target in BCES-induced cutaneous injury. DNA synthesis is inhibited by exposure to BCES which could relate to the mustard's cytotoxic effect. The effects of BCES on the cell cycle in keratinocytes synchronized by aphidicolin were investigated. Primary keratinocytes synchronized at the G1/S boundary entered the S, G2, M, and G1 phases at successive times after release from the block. When cells were exposed to 1, 10, or 50 microM BCES in different phases of the cell cycle, cells in the S phase were more sensitive to BCES than cells in the other phases. Keratinocytes exposed to 1 microM BCES at the G1/S boundary exhibited a prolongation of the S phase and a block in the G2 phase. When these cells were exposed to 10 or 50 microM BCES, they did not enter the S phase for up to 12h and the incorporation of thymidine into DNA was inhibited. These results suggest that the blocks in the G2 and G1 phases relate to the cytotoxic effect of BCES on the germinative population of epidermal keratinocytes.

Animals↗

PubMed1995

Growing a stratified, cornified primary culture of rat keratinocytes with epidermis-like water permeation barrier function.

The culture of cutaneous keratinocytes grown on a Puropore nylon microporous membrane at the air-liquid interface has been shown to be similar to the epidermis in a number of molecular and morphologic characteristics but to exhibit a significantly greater degree of tritiated water permeation. Various culture conditions have been altered in an effort to improve the water barrier properties. A Kp value in the range of 5.5 +/- 1.6 x 10(3) has been obtained for 79% of the cultures a) by plating 0.9 x 10(6) viable basal cells on a piece (13-mm diameter) of membrane for 7 days of submerged growth, b) by placing two membranes on two stacked glass fiber filters (47-mm extra-thick) in a culture dish (60 mm) for 14 days of growth at the air-liquid interface, c) by replacing the growth medium, i.e., 1 ml of complete minimum essential medium (CMEM) every 24 h after lifting, d) by using 10% fetal bovine serum (FBS) in the CMEM during the submerged culture period and 15% FBS in the CMEM during the lifted culture period, and e) by adding a dialysis membrane on top and a Puropore nylon membrane below the culture when the cultures were inserted in the permeation cell for testing. The percentage of cultures with this value for Kp can be increased to 90% if only cultures with yellow, smooth, and shiny surfaces are tested. This system should be useful as a replacement for skin in testing the cutaneous permeation of some chemicals.

Animals↗

PubMed1995

Use of human pseudo-epidermis to evaluate the toxicity of bis-(2-chloroethyl)sulfide (BCES) on water permeation barrier formation and function.

Human pseudo-epidermis was used to investigate the effects of bis-(2-chloroethyl)sulfide (BCES) on the formation and function of the water permeation barrier. To generate the culture, 2 million viable basal cells derived from human skin were placed on a Puropore nylon microporous membrane pre-coated with calf skin collagen. Addition of bovine pituitary extract and epidermal growth factor to the medium favored the formation of homogeneous cultures and better barrier function. The water permeation constant (Kp) was shown to decrease significantly and reached 25 +/- 6 x 10(-3) when it was calculated from 71% of the cultures prepared. The effects of topically applied BCES on the incorporation of [14C]linoleic acid, as a marker for lipid synthesis, and Kp, as a measure of water permeation, were studied. Compared with untreated cultures, there was no difference in the Kp immediately after exposure to 1-10 nmol BCES/cm2 for 30 min. On the other hand, [14C]linoleic acid incorporation was dose-dependently decreased immediately after exposure and then returned to normal by 48 h later. These data suggest that BCES produces no direct damage to the water permeation barrier but may affect barrier formation by inhibiting lipid synthesis.

Adult↗

PubMed1994

Failure to observe a relationship between bis-(beta-chloroethyl)sulfide-induced NAD depletion and cytotoxicity in the rat keratinocyte culture.

It has been proposed that the activation of poly(ADP-ribose) polymerase (Papirmeister et al., 1985), which results from the presence of strand breaks in bis-(beta-chloroethyl)sulfide (BCES) damaged DNA, causes depletion in the level of nicotinamide adenine dinucleotide (NAD) leading to cell death. This hypothesis has now been evaluated in the primary submerged culture of rat keratinocytes. The DNA content, the viable cell number, and the proliferative capability (measured by thymidine incorporation) of the culture were all reduced 48 h after exposure to 10 microM BCES. However, the total NAD level, that is, NAD+ plus NADH, was not changed at a dose of BCES lower than 50 microM. This observation was the same in both proliferating and early differentiating cultures. To further test this hypothesis, the modifying effect of inhibiting poly(ADP-ribose) polymerase on cytotoxicity in BCES-exposed cells was investigated. After exposure to 250 microM BCES, the NAD level was reduced to approximately 26 pmol/micrograms DNA. This value was increased to 34-49 pmol/micrograms DNA at both 24 and 48 h postexposure when the cultures were incubated in medium supplemented with 1-10 mM nicotinamide. Nevertheless, the decrease in the DNA content of the culture was not reversed. These results suggest that in the rat keratinocyte culture exposed to BCES, depletion of NAD is not a prerequisite for cell death.

Animals↗

PubMed1992

Differentiative changes in fucosyltransferase activity in newborn rat epidermal cells.

An enzymatic activity catalyzing the transfer of L-fucose from GDP-L-fucose to a glycoprotein that is associated with the surfaces of the basal cells has been found in the membranous fraction of the cutaneous epidermis from the newborn rat. This fucosyltransferase which is located in the differentiated cells alters the acceptor glycoprotein's lectin-binding specificity from the Isolectin I-B4 of Griffonia simplicifolia (GS I-B4) to the Agglutinin I of Ulex europeus (UEA) and could be responsible for the same change in lectin-binding specificity that occurs as the epidermal basal cell differentiates. Another membraneous fucosyltransferase that can use asialofetuin--but not the GS I-B4-binding glycoprotein--as an acceptor, is also present in the membraneous fraction.

Animals↗

PubMed1992

The effect of 2,2'-dichlorodiethyl sulfide on DNA synthesis of a murine stratified keratinocyte culture system.

A primary stratified keratinocyte culture resembling the epidermis in situ was used as a model for studying the effects of exposure to 2,2'-dichlorodiethyl sulfide, or sulfur mustard (SM), on DNA synthesis. A method that distinguishes between semi-conservative (s.c.) DNA synthesis and repair synthesis was used to determine if the former was inhibited following treatment with SM. In this method the density of the newly synthesized DNA was increased by incorporation of 5-bromo-2-deoxyuridine. Density gradient centrifugation was then used to isolate the heavy DNA for quantification. It was demonstrated that topically applied SM in the dose range of 1-10 nmole/cm2 inhibited s.c. DNA synthesis (replication) in a dose and time related manner. Inhibition of DNA replication by SM would result in inhibition of cell division which must be preceded by s.c. DNA synthesis. This failure to replace damaged germinative cells may lead to the destruction of the basal layer which is observed in vivo and in our epidermal culture following exposure to SM. This may also be related to development of vesication observed in exposed intact human skin.

Animals↗

PubMed1991

Effect of bis(beta-chloroethyl)sulfide (BCES) on base mismatch repair of DNA in monkey kidney cells.

Sulfur mustard, bis(beta-chloroethyl)sulfide (BCES), a bifunctional alkylating agent, is a vesicant whose mode of action involves interference with the integrity of cellular DNA. Alkylation of DNA is responsible for some of the biological effects of BCES in tissue. Another possible mechanism by which BCES could exert its toxic effect is interference with high fidelity repair of damaged DNA. This study evaluated the possible effects of BCES on the repair of specific errors, i.e., mismatched bases, in the DNA. Heteroduplex (ht) DNA, formed between two temperature-sensitive mutants of SV40 virus, tsA239 and tsA255, each having a different point mutation in the gene for large T antigen, was used to study the effect of BCES on mismatched base repair in African green monkey kidney (AGMK) cells. AGMK cells were exposed to dilute solutions of BCES in methylene chloride (MC) prior to cationic lipofection with ht DNA. In order for the cells to produce wild type (wt) SV40 DNA at a nonpermissive temperature (41 degrees C), repair of at least one of the two mismatches in the DNA had to occur. It was observed that (a) as the concentration of BCES was increased, a proportionally longer delay in the appearance of wt DNA at 41 degrees C was observed in treated cells transfected with ht DNA as compared with cultures exposed to MC alone and then transfected with ht DNA, (b) there was no such effect in exposed AGMK cells transfected with wt DNA, (c) wt and ht DNA were transfected at similar rates in unexposed cells, and (d) BCES did not affect the rate of transfection of wt cells. These observations are consistent with the hypothesis that BCES affects mismatched base repair.

Animals↗

PubMed1991

Assessment of the role of DNA damage and repair in the survival of primary cultures of rat cutaneous keratinocytes exposed to bis(2-chloroethyl)sulfide.

Toxicity manifests itself as vesication in human skin exposed topically to bis(2-chloroethyl)sulfide (BCES). The destruction of the proliferating population of epidermal cells is a major component of the pathogenic process. Available data strongly suggest that damage to cellular DNA is a critical factor in the loss of these cells. However, the influence of DNA repair on this toxic response has not been adequately studied. Therefore, a study was undertaken to ascertain the influence of DNA repair on the survival of primary monolayer cultures of rat cutaneous keratinocytes exposed to BCES. The sensitive nucleoid sedimentation assay was employed for the determination of DNA damage in cultures exposed to very low levels of BCES. Initial experiments demonstrated that within 1 hr of exposure to as little as 0.1 microM BCES the structural integrity of cellular DNA was compromised, presumably resulting from the appearance of single-strand breaks in the nucleic acid. This same effect was demonstrated in basal cells derived from a stratified, cornified culture grown at the air-liquid interface and exposed topically to the vesicant. Further studies with the monolayer culture demonstrated that the gross structural integrity of the DNA in cells exposed to as much as 5 microM BCES was completely restored within the first 22 hr following the exposure. However, this repair process appeared to be inefficient since a depression of thymidine incorporation into DNA and a significant loss of DNA were exhibited in exposed cultures as long as 72 hr after the initial exposure.

Animals↗

PubMed1990

Stratified cornified primary cultures of human keratinocytes grown on microporous membranes at the air-liquid interface.

It was previously reported that rat keratinocytes grown at the air-liquid interface on collagen gels or on nylon membranes produce multilayered cultures of uniformly stratified cells, comparable to the epidermis in situ by morphological and biochemical criteria. A protocol has now been developed by which primary human keratinocytes grown for two weeks submerged on microporous nylon membranes and raised to the air-liquid interface for an additional three weeks, exhibit most of the comparable characteristics of the epidermal cells in vivo. Staining with fluorescein isothiocyanate-conjugated monoclonal antibodies indicated the presence of 56,5 and 65-67 kDa keratins as well as filaggrin-type proteins in the upper cellular layers. Desmosomes, lamellar granules and keratohyalin-like granules were observed. Cultures were covered with layers of cornified cells. This study differs from the majority of other investigations on human keratinocytes in that no feeder layers or other biological substrata were used. This system should be useful in toxicological studies of chemicals which are to be applied topically to the skin.

Antibodies, Monoclonal↗

PubMed1990

Levels of cytochrome P-450-mediated aryl hydrocarbon hydroxylase (AHH) are higher in differentiated than in germinative cutaneous keratinocytes.

Induction of microsomal aryl hydrocarbon hydroxylase and cytochrome P-450 was observed in epidermal cells obtained from the skin of newborn rats exposed to benz(a)anthracene by topical exposure and in submerged cultures exposed to the procarcinogen in vitro. The level of aryl hydrocarbon hydroxylase activity was increased 2.5-fold in vivo and six- to sevenfold in vitro when the measurements were made on the entire epidermis or the entire culture, respectively. However, separate measurement on germinative (basal) and on differentiated cells revealed that AHH was sevenfold higher in differentiated cells as compared with basal cells in the skin of both unexposed animals and animals exposed in vivo. Similar results were obtained in cultured cells exposed in vitro. Immunocytochemical staining of sections of skin from animals exposed to benz(a)anthracene in vivo with a monoclonal antibody generated against cytochrome P-450c showed a higher binding of the antibody in lower spinous cells than in basal cells in the epidermis. Although more stained cells were observed in exposed cultures than in untreated cultures, the antibody, which inhibits at least 85% of the hydroxylase activity in the skin, inhibited only 6%-16% of the activity in culture. These observations support the interpretations that a) differentiated keratinocytes have a higher capacity in the metabolic activation of PAH than do germinative cells, although both types of cell are susceptible to induction of cytochrome P-450 by exposure to BA, and b) the cytochrome P-450 induced by exposure of epidermis to benz(a)anthracene in vivo exhibits some differences from the one induced upon exposure of keratinocytes to this procarcinogen in vitro.

Animals↗

PubMed1990

Pseudoepidermis, constructed in vitro, for use in toxicological and pharmacological studies.

The purpose of this study was to establish the validity of the stratified, cornified keratinocyte culture as a model for investigating cutaneous toxicities. This pseudoepidermis, grown on a nylon membrane at the air-liquid interface, responded to topical application of a known vesicant similarly to the response of the tissue in vivo. Alterations in the morphology of the in vitro model also resembled pathological changes seen in in vivo models after exposure to this agent. The effects of the skin irritants benzoate and salicylate on protein and DNA synthesis in the culture were also similar to those observed in vivo.

Animals↗

PubMed1989

Characterization of a cDNA clone encoding human filaggrin and localization of the gene to chromosome region 1q21.

Filaggrins are an important class of intermediate filament-associated proteins that interact with keratin intermediate filaments of terminally differentiating mammalian epidermis. They show wide species variations and their aberrant expression has been implicated in a number of keratinizing disorders. We have isolated a cDNA clone encoding human filaggrin and used this to demonstrate that the human gene encodes a polyprotein precursor containing numerous tandem filaggrin repeats. This structure is similar to that of mouse; however, the human filaggrin repeat is much longer (972 base pairs; 324 amino acids) and shows little sequence homology to the mouse protein. Also, data presented here reveal that the human filaggrin repeats show considerable sequence variations; such polymorphism is not found in the mouse. Furthermore, chromosomal mapping data revealed that the human gene is located at 1q21, indicating that the polymorphism is confined to a single locus. By peptide mapping, we define a short linker sequence within the human filaggrin repeat that is excised by proteolysis to yield functional molecules. Finally, we show by in situ hybridization that human filaggrin precursor gene expression is tightly regulated at the transcriptional level in terminally differentiating epidermis and that this represents a useful system in which to study intermediate filament-intermediate filament-associated protein interactions as well as disorders of keratinization.

Amino Acid Sequence↗

PubMed1989

Human lipoprotein influence on the partition of 2,2',4,4',5,5'-hexabromobiphenyl between 3T3L1 adipocytes and culture medium.

A previous study established that 2,2',4,4',5,5'-hexabromobiphenyl (HBB) entered 3T3L1 adipocytes in culture by passive diffusion from the surrounding medium. The extent to which HBB accumulated within the cell was mediated by the level of triglyceride in the cell. The present study was concerned with the conditions that would facilitate HBB removal from adipocytes as part of a continuing effort to establish an effective and safe technology for reducing body burdens of lipophilic xenobiotics. Addition of human lipoprotein to the culture medium increased HBB removal from preloaded adipocytes 18 to 80 times more than did the addition of other blood proteins. Lipoproteins also decreased equilibrium deposition of HBB in the cells. The order of effect was low-density lipoprotein (LDL) much greater than high-density lipoproteins (HLD) greater than very-low-density lipoproteins (VLDL). These results are consistent with the hypothesis that lipoproteins act as a depot by binding HBB to immobilize the xenobiotic in the medium. The rate of removal of HBB was correlated with concentrations of lipoprotein cholesterol, cholesterol ester, and phospholipid in the culture medium (r greater than .95). Total lipoprotein fractions from individuals with high levels of serum cholesterol significantly increased HBB removal from preloaded adipocytes when compared with lipoproteins from normal human serum. Decreased removal was observed with lipoproteins from individuals with low serum cholesterol or triglyceride. These results suggest that cholesterol and/or cholesterol esters in the blood play an important role in both delivery and removal of HBB from the adipose tissue. Evidence has been presented that supports the hypothesis that HBB moves freely across the adipocyte membrane and is sequestered in either the cell or pseudoblood according to its relative solubility in these compartments.

Adipose Tissue↗

PubMed1988

bis-(beta-chloroethyl)sulfide (BCES)-induced changes in epidermal cell homeostasis in vitro.

A rat cutaneous keratinocyte culture system was developed to study the effects of the vesicant bis-(beta-chloroethyl)sulfide (BCES) on the homeostasis of cell proliferation and differentiation. Lectins were used to reveal cell surface carbohydrate changes as the keratinocytes differentiate. In the newborn rat epidermis, the isolectin, Griffonia simplicifolia I-B4 (GS I-B4), binds to basal cell surfaces. Ulex europeus agglutinin I (UEA) binds to the surfaces of spinous and lower granular cells and is therefore considered an indicator of keratinocyte differentiation. A fluorometric assay was developed which determines the ratio of bound UEA to bound GS I-B4 (the UEA/B4 ratio) in primary monolayer cultures of rat cutaneous keratinocytes maintained in low Ca2+ medium. The UEA/B4 ratio was found to be a representation of the relative sizes of the differentiating and proliferating cell compartments in the monolayer cultures, respectively (W.W. Ku and I.A. Bernstein, 1988, Exp. Cell Res., 175, 298-316). Monolayer cultures exposed for 1 hr to BCES at Day 1 exhibited a dose-related increase in the UEA/B4 ratio at Day 7 when compared to solvent controls. The results from the analysis of lectin binding sites showed a decrease in GS I-B4 binding with little or no change in UEA binding as a result of BCES exposure, contributing to the increase in the UEA/B4 ratio. BCES-exposed monolayers also showed early perturbations in replicative DNA synthesis as revealed by autoradiography. Subsequent to the perturbations in replicative DNA synthesis was an inability of BCES-exposed cultures to produce cells into the monolayer through mitosis. In addition to an increase in the UEA/B4 ratio, BCES-exposed monolayers also showed a dose-related loss of DNA, with the appearance of enlarged cells at Day 7. These enlarged cells failed to show evidence of DNA synthesis, with groups of these cells showing intense UEA staining with only faint GS I-B4 staining. Overall, exposure to low concentrations of BCES appeared to disrupt the normal homeostasis of cell proliferation and differentiation in this monolayer culture system. This disruption was primarily through a reduction in the fraction of germinative (basal) cells with concomitant retention of some early differentiated cells, presumably early spinous or spinous cells.

Alkylating Agents↗

PubMed1988

Lectin binding as a probe of proliferative and differentiative phases in primary monolayer cultures of cutaneous keratinocytes.

The surface of cells in the cutaneous epidermis of the newborn rat exhibits a discrete change in lectin-binding specificity from Griffonia simplicifolia I-B4 (GS I-B4), specific for alpha-D-galactosyl residues, to Ulex europeus agglutinin I (UEA), specific for alpha-L-fucose, as the cell leaves the basal layer and differentiates. Primary monolayer cultures of rat keratinocytes maintained in low Ca2+ medium (0.08 mM) exhibited a characteristic unimodal pattern in the ratio of bound UEA to bound GS I-B4 (UEA/B4 ratio) over a 7-day culture period as determined by a quantitative fluorometric assay. The UEA/B4 ratio was initially low between Days 1 and 2 (0.56 +/- 0.05), steadily increased to a maximum of 0.84 +/- 0.09 between Days 2 and 4, and then gradually decreased to 0.41 +/- 0.07 between Days 6 and 7. Estimation of DNA synthesis showed (a) a higher [3H]thymidine incorporation when the UEA/B4 ratio was low and (b) a steady but lower incorporation between Days 3 and 4, coincident with the higher UEA/B4 ratio. Autoradiographic results further showed that cells stained intensely with UEA failed to incorporate [3H]thymidine into their nuclei. Electrophoresis of [3H]fucose-labeled material isolated on UEA-Sepharose 4B revealed that the changes in labeling by [3H]fucose, bound UEA, and the UEA/B4 ratio in the monolayer were related in part to variable expression of "96K-associated UEA-bound" radioactivity corresponding to a major class of lectin-specific cell-surface glycoproteins (GP96 fraction) identified in situ. Overall, the results suggest that (a) the increase in the UEA/B4 ratio between Days 2 and 4 reflects the progression of a proportion of the cells in the monolayer to an early spinous cell stage, the ultimate fate of which is desquamation into the medium and (b) the decrease in the UEA/B4 ratio between Days 5 and 7 reflects a consequent proliferative response to this loss of cells. This system should be useful for studying environmental influences on the homeostasis of cell proliferation and differentiation in the cutaneous epidermis.

Animals↗