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Biomedical subjects

K Mah

Publications and source records attributed to K Mah.

29 records · Page 2Linked to original sources

Theophylline effects on normal uveal melanocytes in culture: an ultrastructural study.

Theophylline enhances maturation and differentiation of uveal melanocytes. By electron microscopy, we showed that theophylline changes small, dendritic melanocytes into large, platelike cells; it also enhances DOPA reaction as evidenced by increased deposition of DOPA reaction products in dilated cisternae and vesicles around the Golgi region. The effect is partially reversible in choroidal melanocytes but irreversible in iridial cells. It appears that theophylline, in addition to inducing tyrosine activity, accelerates the maturation and/or aging that normally occurs in cultured melanocytes when incubation is prolonged.

Animals↗

Gossypol effects on cultured normal and malignant melanocytes.

Gossypol, a polyphenolic compound known to interfere with spermatogenesis, was found to have differential cytotoxic effects on normal and malignant melanocytes in culture. Ultrastructurally it caused marked swelling and vacuolization of mitochondria; there was an almost complete loss of cristae but the outer mitochondrial membrane was retained. The cytotoxicity seemed to be selective for actively proliferating cells, regardless of normal or malignant origin. An endothelial cell line (RF/6A) derived from the choroid-retina of the eye of a rhesus fetus was extremely sensitive to its toxic effect. The mechanism of action is still unknown. The fact that mitochondria are predominantly damaged suggests that toxicity involves a perturbation of energy metabolism and the membrane transport system.

Animals↗

Effects of dicarboxylic acids on normal and malignant melanocytes in culture.

We have shown that dicarboxylic acids (C9 and C12), known competitive inhibitors of tyrosinase, are selectively cytotoxic to malignant melanogenic melanocytes but not to normal pigmented cells or to amelanotic or non-melanogenic melanoma cells. The main target of this toxicity appears to be the mitochondria, which become markedly swollen and vacuolated. The mechanism of their action has been thought to be due to interference with oxidoreductases in the mitochondria. However, our results suggest that this cytotoxicity most probably does not result simply from inhibition of mitochondrial enzymes, but is closely related to the melanin biosynthesis pathway.

Animals↗

Dermal melanocytes and elastic fibers.

The relationship between dermal melanocytes and elastic fibers was studied by electron microscopy. In 3 patients with dermal melanocytosis, the long cytoplasmic processes of the melanocytes were aligned along the long axis of the elastic fiber, and encircled or embraced these fibers. The same intimacy existed between melanocytes and elastic fibers in the skin of cynomolgus macaques, who normally have dermal melanocytes. These findings suggest that dermal melanocytes, for reasons yet to be determined, interact with elastic fibers under these special conditions.

Aged↗

Dermal Merkel cells in the nevus of Ota and leopard syndrome.

We observed dermal Merkel cells around vellus hair follicles in one patient with nevus of Ota and one with leopard syndrome. These Merkel cells were in contact with Schwann cells and nerve endings in the dermis. The question of whether or not Merkel cells exist normally in adult dermis remains unanswered. However, their presence in these abnormal conditions suggests that normally they do occur in the dermis but go undetected because their numbers are so few or they are in a form not readily identifiable by currently available methods.

Abnormalities, Multiple↗

Changes in melanosomes with age in iridial stromal melanocytes of rhesus macaques.

Iridial ultrasections from eyes of rhesus macaques of different ages were compared. Long, thin melanosomes characteristic of iridial stromal melanocytes occur singly in young monkeys prior to or until adolescence (at or under 3 years of age); as monkeys grow older, they begin to form compound granules by fusions of two or more melanosomes. The frequency of fusions and the number of melanosomes in the fused granules increase in proportion to the age. It appears that long, thin single melanosomes fuse and develop into large ovoid granules characteristic of those in adult choroidal melanocytes and in postnatal pigmented epithelia. We suggest that iridial melanocytes in due time develop into cells with properties identical to those of choroidal melanocytes: they have the same developmental history, and differ only in the timing of their maturation and terminal differentiation.

Aging↗

Theophylline and melanocyte-stimulating hormone: effects on uveal melanocytes of adult rhesus eyes.

The effects of theophylline and melanocyte-stimulating hormone (MSH) on cultured uveal melanocytes from the eyes of normal adult rhesus macaques were studied by light and electron microscopy and by dopa cytochemistry. The principal effects were changes in melanosome ultrastructure and an increased complexity of Golgi-associated vesicles and cisternae filled with dopa reaction products. The changes were more extensive in iris cells and less remarkable in choroid cells. The effects of theophylline were more pronounced than those of MSH. Our data suggest that normal iridial melanocytes, as do melanogenic murine melanoma cells, respond to theophylline or MSH by increasing tyrosinase synthesis, tyrosinase transfer, and melanization.

Animals↗

Electron microscopic and cytochemical observations of theophylline and melanocyte-stimulating hormone effects on melanoma cells in culture.

The effects of theophylline and melanocyte-stimulating hormone on B16 melanoma cells in culture cells were studied by electron microscopy and dopa cytochemistry. The data show that theophylline and melanocyte-stimulating hormone enhance melanogenesis by activating tyrosinase synthesis and its transfer but that neither affects the synthesis of the well-organized eumelanosome matrix. Their pigmenting effects appear to be limited to the melanogenic cells and result from a marked increase, particularly in theophylline-treated cells, in pheomelanosome formation.

Animals↗

Assessment of acute radiation-induced pulmonary changes using computed tomography.

In a prospective study of acute radiation-induced pulmonary changes, CT scans of 54 patients were performed before and at preselected times during the 6 months following fractionated radiation therapy of the thorax. The CT films were evaluated independently by three diagnostic radiologists and 36 patients were scored as having postirradiation pulmonary findings. The average interobserver agreement for this scoring was approximately 85%. The end point was observed as an increase in lung density within the irradiated volume on a follow-up CT examination. All 36 patients demonstrated lung opacities in an irregular, homogeneous, or nonhomogeneous pattern within the radiation beam boundaries. In addition, the following characteristics were observed at various frequencies in these 36 patients: extension of the changes across anatomic tissue boundaries (50%), air bronchograms (25%), loss of lung volume (15%), and pleural thickening (15%). Confinement of the findings within the irradiated volume was the only specific characteristic of postirradiation changes. In two patients the changes appeared as sharply defined, nodular opacities and were considered to be atypical of radiation damage. These were subsequently confirmed to be metastases. Prospective assessment of an adequate number of patients has helped to establish the CT appearance of acute radiation-induced pulmonary effects and, hence, to minimize its confusion with malignancies and other abnormalities.

Adolescent↗