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Biomedical subjects

A J Cox

Publications and source records attributed to A J Cox.

At least 73 records · Page 4Linked to original sources

Separation of human skin cells by velocity sedimentation into functionally distinct fractions.

The epidermis consists of a heterogeneous population of cells including Langerhans cells, Merkel cells, melanocytes, and keratinocytes in various stages of differentiation. The current study was undertaken to determine if skin cell suspensions can be separated into morphologically and/or functionally distinct fractions. Skin cells were suspended by trypsinization and separated into multiple fractions by velocity sedimentation. Certain fractions reproducibly stimulated proliferation of allogeneic lymphocytes in the skin cell lymphocyte reaction, whereas other fractions, containing larger cells, supported growth of keratinocyte colonies in cell cultures. These results indicate that stimulation in the skin cell lymphocyte reaction and growth of keratinocyte colonies are mediated by distinct cells, separable by velocity sedimentation.

Cell Division↗

Lentigo maligna melanoma in a treated psoriatic plaque.

Lentigo maligna melanoma developed in a patient with a 41-year history of psoriasis. The patient had received substantial radiation therapy and limited tar and ultraviolet energy therapy to the site at which melanoma developed. We raise the question of whether the carcinogenic modalities used to treat the patient may have influenced the development of melanoma.

Female↗

The mitotic index in psoriatic plaques and their response to PUVA therapy.

The mitotic index of pretreatment plaques of chronic psoriasis was determined before treatment with PUVA. There was a wide variation in mitotic indices in different patients. Treatment was given with UV-A 2 h after oral ingestion of 8-methoxypsoralen (8-MOP) two or three times per week, with increasing doses of UV-A. Patients were considered cleared if there was 95% clearing of all psoriatic plaques. There was no correlation between the mitotic index and the response to treatment, as measured by either the number of joules administered or the number of treatments until the lesions cleared. This suggests that the action of PUVA in psoriasis is not dependent on the amount of increase in epidermal proliferation.

Humans↗

Epidermal dystrophy. Occurrence after psoriasis therapy with psoralen and long-wave ultraviolet light.

Focal dystrophy of epidermal cells has been recognized in about half of 37 patients treated with psoralen and long-wave ultraviolet radiation (PUVA) for psoriasis. This lesion appeared in many patients by the end of the clearing phase of therapy and was present to a similar degree one year after the beginning of the treatment. It is probable that most such changes are transient, but the appearance suggests the possibility that cells have undergone somatic mutation that potentially could be dangerous.

Epidermis↗

Amyloid deposition after psoriasis therapy with psoralen and long-wave ultraviolet light.

Histologic examination of skin from 52 patients under continued treatment with methoxsalen and long-wave ultraviolet irradiation (PUVA) disclosed small superficial dermal deposits in six subjects who had completed one year of therapy and in six subjects who had completed two years of therapy. These deposits, by light and electron microscopic criteria, are similar to those of lichen amyloidosus. Amyloid deposition should be regarded as a possible complication of PUVA therapy.

Amyloidosis↗

Subcutaneous mycosis fungoides.

In five cases of mycosis fungoides, previously treated with electron-beam therapy, subcutaneous nodules developed. Clinically, these lesions were thought to be epidermoid cysts or lipomas, but on biopsy were discovered to be subcutaneous infiltrates, three of which were diagnosed as mycosis fungoides. The other two specimens showed only a nonspecific subcutaneous infiltrate. There is no ready explanation for the appearance of these lesions, but it is speculated that they may be the result of inadequate penetration of the electron beam to the depth at which some atypical cells may originally have been located. Patients with mycosis fungoides who develop unusual subcutaneous nodules should be fully investigated so that appropriate and adequate therapy may be initiated.

Adult↗

Ultrastructural changes in nuclei and nucleoli in psoriatic epidermis during and after PUVA therapy.

Quantitative and qualitative changes of the nuclei and nucleoli in psoriatic epidermis at different intervals during therapy with psoralen and long-wave ultraviolet light (PUVA) were revealed with the electron microscope. Early in the therapy (24 to 96 hr after commencing treatment) changes occur, including irregularity of the nuclear envelope, enlargement of the nuclei and nucleoli, temporary disappearance of fibrillar centres, followed by temporary disappearance of fibrillar centres, followed by temporary increase in nuclear bodies and increasing amounts of heterochromatin. After clearing of lesions, the nuclear and nucleolar structures were identical with those of normal keratinocytes, except that the relative amount of heterochromatin was greater. It is suggested that PUVA therapy brings about inhibition of abnormal keratinization, possibly due to gene repression, and that this may be related to changes in the fibrillar centres of psoriatic keratinocyte nucleoli.

Adolescent↗

Ultrastructural studies of nuclei and nucleoli in psoriatic epidermis, compared with those in normal epidermis.

Quantitative and qualitative differences of the nuclear and nucleolar structures in normal and psoriatic (involved and uninvolved) epidermis were revealed with the electron microscope. The size of nuclei and nucleoli was increased, the frequency of nuclear bodies was increased, and the relative amount of heterochromatin was decreased in involved skin compared to normal or uninvolved skin. There was no significant difference between normal skin and uninvolved skin of psoriasis. In addition to these changes, multiple fibrillar centers within nucleoli and small masses of chromatin in the epidermal nucleoplasm were observed very frequently in involved skin, while rarely or not at all in normal and uninvolved skin. These results suggest that involved psoriatic keratinocytes have increased metabolic activity and abnormal protein synthesis, having undergone gene derepression.

Adolescent↗

Pigmented lesions in newborn infants.

1058 newborn infants were examined. Forty-one (3-9%) had clinically discernible pigmented lesions compatible with melanocytic naevi. Biopsy was performed on thirty-four of the forty-one and of these; eleven, representing 1-01% of the infants, proved to be melanocytic naevi. No giant (garment) naevi were seen in this series. Two of the eleven naevi pathologically examined showed histological changes similar to those that have been reported in some giant naevi, but the remaining nine were not only different from criteria usually assigned to giant naevi, but they also differed from the usual adult naevi, in that most were predominantly junctional. None of the melanocytic naevi in this series showed any suggestion of malignant change. In newborn infants it is often impossible clinically to distinguish naevi from other types of pigmented lesions, as only eleven out of the thirty-four pigmented lesions were melanocytic naevi. Seven of the eleven melanocytic naevi were under 1-5 cm in diameter. No pigmented lesions were found on the palms, soles or genitalia.

California↗

Debranching enzyme from rabbit skeletal muscle. Purification, properties and physiological role.

Debranching enzyme was purified 150-fold from rabbit skeletal muscle by a three-step procedure which utilised ammonium sulphate precipitation, ion-exchange chromatography on DEAE-cellulose and "hydrophobic" chromatography on Sepharose-NH(CH2)4NH2. The preparation was completed within three days, and 200 mg enzyme was isolated from 1000 g muscle, which represented an overall yield of 60%. The preparation was homogeneous by the criteria of polyacrylamide gel electrophoresis and ultracentrifugal analysis. The sedimentation coefficient, s20,w, was 8.1 S. The amino acid composition was determined, and the absorption coefficient, A280 1%, measured refractometrically was 17.5. The subunit molecular weight determined by gel electrophoresis in the presence of sodium dodecyl sulphate was 166000 and this value was supported by sedimentation equilibrium in the presence of 6 M guanidinium chloride (1550oo). The molecular weight of the native enzyme measured by high-speed sedimentation equilibrium was 164000, showing that the debranching enzyme is a monomeric protein at the concentrations which exist in muscle (0.7 mg/ml). The results indicate that the two different enzyme activities which are associated with debranching enzyme, 1,4-glucan-4-glycosyltransferase and amylo-1,6-glucosidase, reside on the same polypeptide chain. Protein-glycogen particles isolated from skeletal muscle showed seven major protein-staining components by polyacrylamide gel electrophoresis, one of which was identified as debranching enzyme. ,our of the other components were the alpha and beta subunits of phosphorylase kinase, glycogen phosphorylase and glycogen synthetase. A new titrimetric assay for debranching enzyme was developed; it was used to demonstrate that the maximum potential activity of debranching enzyme is only 5--10% that of phosphorylase at the concentrations of the two enzymes in skeletal muscle. Since the activity of debranching enzyme is unaffected by every mechanism which leads to the activation of glycogen phosphorylase and phosphorylase kinase, the evidence suggests that the hormonal control of muscle glycogenolysis by adrenalin might be confined to a stimulation of rate of degradation of the outermost branches of glycogen.

Amino Acids↗