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Biomedical subjects

R Mackie

Publications and source records attributed to R Mackie.

At least 37 records · Page 2Linked to original sources

A prospective study of the histological changes in the skin in patients receiving bone marrow transplants.

Fourteen patients who received a bone marrow transplant (BMT) as treatment for leukaemia were included in a prospective study of the histological changes in the skin. The aim of this study was to improve the early diagnosis of graft-versus-host disease (GVHD). It was found that the clinically 'normal' pre-transplant skin was in some cases histologically abnormal on H & E examination in patients who were on regular maintenance cytotoxic chemotherapy. These changes were similar to some of the features of GVHD. Immunocytochemistry, although not specific, was found to be helpful in the diagnosis of some cases of GVHD. Suggestive features included a reduction in the numbers of Langerhans cells, an increase in the number of suppressor (OKT8+) cells in the dermal infiltrate and the presence of Ia positivity of the keratinocytes in the epidermis.

Adult↗

Inhibition and recovery of DNA synthesis in PHA-stimulated u.v.-irradiated lymphocytes from patients with actinic keratosis.

The recovery, after inhibition by u.v.-irradiation, of phytohaemagglutinin-stimulated DNA synthesis is impaired in lymphocytes from patients with multiple actinic keratoses (AK) compared to the recovery in lymphocytes from age-matched, control individuals. This shows that the reduced level (50%) of DNA repair activity in AK cells is sufficiently different from that in normal cells to significantly affect cellular activity.

DNA Repair↗

Paradoxical response of malignant melanoma to methotrexate in vivo and in vitro.

Methotrexate (MTX) shows consistent cytotoxicity for melanoma cells in vitro but it is ineffective in clinical use at equivalent concentrations in vivo. This apparent paradox has been investigated by cell culture techniques and results quantified by cell number. In an in vitro model of high dose MTX therapy followed by leucovorin rescue (HD-MTX-LCR) there was survival of both melanoma and choriocarcinoma cell lines but not of an acute lymphocytic leukaemia cell line. The 70H metabolite of MTX was identified by HPLC in plasma samples of melanoma patients treated by HD-MTX-LCR, in which MTX concentrations approximately 10(-5) M were maintained for 24 h. However, metabolism per se is unlikely to account for the lack of response to MTX clinically. In vitro 70H MTX (10(-7) - 10(-6) M) was two orders of magnitude less cytotoxic for melanoma than MTX (10(-9) - 10(-8) M). The cellular accumulation of [3H]-MTX, using a rapid gradient centrifuge technique for separation of melanoma cells from medium, was reduced in the presence of 70H-MTX. The results suggest that reduced cellular uptake of MTX combined with biochemical rescue of tumour cells may partially explain the paradoxical lack of clinical response of melanoma to the drug.

Animals↗

Epidermolysis bullosa in association with aplasia cutis congenita and pyloric atresia.

A female infant born to a mother who had an elevated serum alpha-fetoprotein during early pregnancy, presented a combination of epidermolysis bullosa and aplasia cutis congenita. She developed evidence of upper gastrointestinal obstruction and died at the age of 43 hours. Post-mortem examination showed the presence of pyloric atresia and electron microscopy of skin biopsies showed epidermolysis bullosa simplex. Examination of the placenta revealed a unique abnormality of the membranes, indicating the existence of two sacs. This case and the previously reported cases, which are reviewed, suggest an autosomal recessive inheritance. Serum alphafetoprotein estimation, ultrasonography and fetoscopy with skin biopsy are suggested as a means of pre-natal diagnosis in future pregnancies.

Abnormalities, Multiple↗

Muscular hypertonia: quantitative analysis.

By a statistical method of analysis, the force applied to move a limb passively can be translated into physiologically relevant parameters relating to the muscle. The parameters identified and measured are the dynamic and static activity of the muscle and their interactions with the varying length of the muscle during stretch. This method of analysis has been shown to be of assistance in evaluating the reflex status of persons with central nervous system disorders in preparation for treatment and in measuring the effects of treatment.

Humans↗

Cellular fine structure in the invasive nodules of different histogenetic types of malignant melanoma.

Ultrastructural studies were carried out on the invasive nodule of forty malignant melanomas. The findings support the concept that the fine structure of lentigo maligna melanoma is often characteristic, and differs from that of superficial spreading and nodular melanoma. The melanosomes in lentigo maligna melanoma are usually ellipsoidal and resemble those of normal melanocytes, whereas the melanosomes in superficial spreading and nodular melanoma are most often spheroidal and abnormal in appearance. Superficial spreading and nodular melanomas cannot be distinguished reliably by their ultrastructure. Melanosomal appearances could not be related to the presence of a pre-existing naevus or the depth of invasion of the tumour nodule.

Humans↗

DNA repair deficiency in lymphocytes from patients with actinic keratosis.

DNA repair activity was measured in peripheral blood lymphocytes from 18 patients with Actinic Keratosis and 18 age-matched control subjects, by comparing the incorporation of 3H-thymidine into cells after irradiation with ultraviolet light with that into unirradiated cells. The incorporation was followed autoradiographically or by measuring acid insoluble radioactivity in cells labelled in the presence of hydroxyurea. The repair activity in lymphocytes from Actinic keratosis patients was only 47.1 percent (+/- 6.5%) of that in cells from the control subjects.

Aged↗

Distribution of HLA antigens in patients with mycosis fungoides.

19 patients with plaque-style mycosis fungoides have undergone determination of HLA antigen distribution. Deviations from the expected distribution frequency occurred with the antigens of the W19 group comprising A29, W30, W31 and W32 and of B8 and A1. The W19 group deviation was statistically significant (chi2 = 9.7 p value less than 0.005). The significance of this observation in relation to reported immunological abnormalities in mycosis fungoides is discussed.

Adult↗

Chronic mucocutaneous candidiasis treated with transfer factor.

A patient with chronic mucocutaneous candidiasis resistant to all tropical therapy has had extensive tests of immunological function carried out before and after administration of transfer factor. Immunological testing has been both specific, directed at responses to candida antigen, and non-specific, directed at general assessment of the patient's immune status. Transfer factor has been administered on three occasions in the past year. After each treatment temporary clinical improvement accompanied by changes in both specific and non-specific immunological responses have been observed. The possible mode of action of transfer factor in this case is discussed.

Adult↗