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P D Mier

Publications and source records attributed to P D Mier.

16 recordsLinked to original sources

Studies on the plasma membrane of normal and psoriatic keratinocytes. I. Preparation of material and morphological characterization.

A method is described for the preparation of isolated keratinocytes suitable for subsequent biochemical studies. Scanning electron microscopy showed that the maturation process is accompanied by an increase in cell size and a shortening and eventual loss of microvilli. Psoriatic keratinocytes are distinguishable by exhibiting longer microvilli at all levels of maturation.

Adolescent

Studies on the plasma membrane of normal and psoriatic keratinocytes. 2. Cyclic AMP and its response to hormonal stimulation.

Cyclic AMP levels have been determined for the first time in isolated keratinocytes. Values were more reproducible than those reported using epidermal slices. Evidence is presented to show that damage to hormone receptors is minimal. Other observations include the following: (1) Keratinocytes from psoriatic lesions showed reduced 'resting' levels of cyclic AMP as well as a diminished response to adrenaline. (2) Cyclic AMP levels were maximal in the basal cells, falling dramatically in fully differentiated keratinocytes. (3) The topical application of a corticosteroid (fluocinolone acetonide) did not modulate the response of adenyl cyclase to hormonal stimulation.

Adolescent

Lysosomal hydrolases of the epidermis. 5. Variation with depth in the cow snout.

The activity of twelve acid hydrolases has been measured in serial horizontal sections of cow snout epidermis. The majority of these enzymes showed a clear peak in the basal and lower spinous cell layers; acid phosphatase, however, was found mainly in the keratinizing zone. These findings suggest that two discrete populations of lysosomes may occur in epidermis. Those present in the lower layers possess a typical pattern of hydrolase activity and probably correspond to the 'orthodox' lysosomes observed by electron microscopy techniques, whereas those found in the keratinizing zone possess an unusual hydrolase profile and may correspond to the bodies identified morphologically as keratinosomes (Odland bodies, membrane-coating granules).

Animals

Lysosomal hydrolases of the epidermis. 6. Changes in disease.

The activities of 14 acid hydrolases have been measured in normal and diseased human epidermis. Our findings were as follows: (i) Increased hydrolase activity was common in lesions; the clinically uninvolved skin of patients, however, invariably showed normal values. (2) The pattern of change was independent of the nature of the didease, the arylsulphatases and beta-glucosidase usually showing the greatest elevations. (3) The magnitude of the changes differed from disease to disease, being most marked in the lesions of psoriasis. (4) Ichthyosiform erythroderma was exceptional in showing elevated levels of the galactosidases and cathepsins B1 and D. We suggest that (with the exception of ichthyosiform erythroderma) the abnormalities which we have observed may be related to the proliferative rate of the epidermis.

Adolescent

A lysosomal storage disorder of the epidermis characterized by a deficiency of alpha-mannosidase and an accumulation of mannose-rich materials.

Laboratory investigation of a patient diagnosed as ichthyosiform erythroderma bullosa revealed the following abnormalities: (1) alpha- and beta-galactosidases were elevated in the lesion. (2) alpha-mannosidase activity was extremely low both in the lesion and in relatively normal epidermis. (3) The mannose:glucose ratio of water-soluble hexose-containing material in the scales was very high. (4) Membrane-limited vacuoles, apparently enlarged secondary lysosomes, were observed. We conclude that this patients is the first documented example of a lysosomal storage disease in which overt clinical lesions are confined to the epidermis.

Adult

Acid hydrolase activity in normal human callus and in psoriatic scales.

The activities of 14 acid hydrolases have been measured in normal human callus and in psoriatic scales. Values for the scales were much higher than for callus. The increase is believed to be the result of two factors: an increased synthesis of these enzymes by the psoriatic lesion and a diminished degree of inactivation during the keratinization process.

Bony Callus

Lysosomal hydrolases of the epidermis. 3. Peptide hydrolases.

Four distinct peptide hydrolases (EC 3-4) have been characterized in guinea-pig epidermis; these are cathepsin B1, cathepsin C, cathepsin D and arylamidase. Their properties are consistent with those of lysosomal enzymes. Cathepsin E was not detected.

Aminopeptidases

Lysosomal hydrolases of the epidermis. I. Glycosidases.

Seven distinct glycosidases (EC 3.2) have been characterized in guinea-pig epidermis. Their properties indicate them to be of lysosomal origin. The 'profile' of the epidermal glycosidases is significantly different from that reported for whole skin, the activities of beta-galactosidase and beta-acetylglucosaminidase being very high and those of the remaining enzymes relatively low in epidermis.

Acetylglucosaminidase

Lysosomal hydrolases of the epidermis. 2. Ester hydrolases.

Five distinct ester hydrolases (EC 3-1) have been characterized in guinea-pig epidermis. These are carboxylic esterase, acid phosphatase, pyrophosphatase, and arylsulphatase A and B. Their properties are consistent with those of lysosomal enzymes.

Acid Phosphatase