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Biomedical subjects

F Hu

Publications and source records attributed to F Hu.

At least 91 records · Page 5Linked to original sources

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↗

False dopa reaction in studies of mammalian tyrosinase: some characteristics and precautions.

In cytochemical studies of B16 melanoma cells with the dopa reaction for tyrosinase, a false positive result that can easily be confused with authentic reactions has been observed. A preliminary characterization of this false reaction in comparison to authentic reactions with respect to stereospecificity, morphological characteristics, and subcellular localization has been conducted. Modifications of the classic dopa method have been devised that minimize occurrence of the false reaction.

Animals↗

Theophylline and melanocyte-stimulating hormone effects on gamma-glutamyl transpeptidase and DOPA reactions in cultured melanoma cells.

Gamma-glutamyl transpeptidase (GGT), an enzyme of the gamma-glutamyl cycle, was demonstrated in 3 of 6 cell lines derived from a single B16 murine melanoma. Its activity in these cells varied a great deal, appeared to be correlated with the developmental cycle of the cells, and was greatest in young, actively melanogenic cells. Generally, the activity seemed parallel to that of tyrosinase, an enzyme specific for melanin synthesis. The levels of both enzymes tended to decline with prolonged in vitro cultivation, but could be readily renewed after one animal passage. The 3 cell lines that were GGT-negative were nonpigmented and DOPA-negative; so was a nonmelanogenic and nonmelanocytic rhesus cell line. Melanocyte-stimulating hormone (MSH) and theophylline both enhanced pigmentation in murine melanoma cells. The mechanisms of their action apparently differed. We found that theophylline increased both DOPA- and GGT- reactive cells, whereas MSH only increased DOPA-reactive cells. All 3 GGT-positive lines were tumorigenic, and 2 GGT-negative line were not tumorigenic. Our observations suggest that GGT plays a role in the melanin biosynthetic pathway and the its activity is greater in melanoma cells that are tumorigenic.

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↗

Gamma-glutamyl transpeptidase in the pigment cells of rhesus eyes.

We demonstrated that gamma-glutamyl transpeptidase, one of the enzymes of the gamma-glutamyl cycle, is present in the melanocytes of the eyes of rhesus macaques. Enzyme activity was detected in active melaninsynthesizing melanocytes of the iris stoma and in fetal and neonatal retinal pigment epithelium. It was not detected in adults retinal pigment epithelium or choroidal melanocytes, which are ontogenetically more advanced in development and have little melanogenic activity. Our data show that gamma-glutamyl transpeptidase activity correlates well with growth, early differentiation, and active melanogenesis, and support the hypothesis that in addition to tyrosinase, a second enzyme, such as gamma-glutamyl transpeptidase, takes part in the melanin and pheomelanin metabolic pathways.

Animals↗

Yellow mutant albinism: cytochemical, ultrastructural, and genetic characterization suggesting multiple allelism.

This report describes three sisters, including monozygotic (MZ) twins, with clinical, ultrastructural, and histochemical features typical of yellow mutant albinism; This form of albinism is clinically similar to the tyrosinase-positive type, but hair bulbs showed (1) organelles similar to red hair pheomelanosomes and (2) absence of tyrosinase activity. Classical tyrosinase-negative albinism was found in a maternal cousin of the probands. Pedigree analysis of this family suggests multiple alleles occupying a single locus.

Adult↗

A reinvestigation of solar lentigines.

Solar lentigines were reinvestigated by a number of different methods to gain a better perspective on their structure. In histologic sections and dopa preparations of split skin, large numbers of melanocytes were seen crowded at the base of the clubbed, budding rete ridges. In split-skin preparations, the scanning electron microscope showed complex systems of ridges, columns, and craters on the underside of the lentiginous epidermis. Oval bodies measuring 15 to 30 mu, with dendrites, were numerous at the apices of the complex epidermal ridges; these bodies were presumed to be melanocytes. In transmission electron micrographs of lentigines, the melanosome complexes inside the keratinocytes were much larger than those found in noninvolved skin. The complex and distinctive architecture of these maculae is probably the result of concurrent proliferation of melanocytes and keratinocytes.

Aged↗