Melanin synthesis activation dependent on inductive influences

Summary Gene activity in melanin-synthesising cells of albino periodic (a^p) mutants ofXenopus laevis is expressed phenotypically in the framework of the following cycle: a period of complete albinism succeeds the short peak of pigmentation, and melanosomes which have formed disappear. Skin and choroid coat melanophores as well as pigmented epithelium melanocytes are involved in this cycle.Parabiosis experiments allowed hormonal regulation of the melanin-synthesising gene activity to be excluded. Neural fold transplantations have shown that there is no inhibitory action on melanophore differentiation from the side of the a^p/a^p recipient.Melanin synthesis in pigmented epithelium of a^p mutants can be activated to level comparable with that of wild-type animals, if eye vesicles of a^p/a^p embryos have been brought into contact with endomesodermal derivatives of +/+ embryos at the early tail bud stage. Contact of eye vesicles of +/+ embryos with the endomesoderm of mutants prevents normal melanogenesis in pigmented epithelium of transplanted eyes. Eye transplantations made after the early tail bud stage have shown that gene expression in pigmented epithelium is independent of any external influences.Data obtained here demonstrate a selective induction of a separate cell type (melanocytes) and the stage-specificity of this process. In the a^p mutant the abnormal melanin synthesis is apparently predetermined by deficiency in the inducer of melanogenesis. Inhibition of melanogenesis by endomesoderm seems to be less probable. Data are discussed in the light of current ideas on the play of gene activity.     

The aged: medical and social aspects

Physical health is affected by physiological aging that impacts on all tissues and organs, notably sensorial systems (hearing, sight), the locomotory and the immunological systems (lowering of resistance to infections). There is an increase with age in the incidence of many cancers (particularly breast, prostate, and colon cancers) and cardiovascular diseases. Regular check-ups are useful in order to take appropriate measures in time. It is important that people maintain regular physical activity and a balanced diet even up to an advanced age and the elderly must learn to adapt themselves to the ever-changing abilities of their organism. It is possible to slow down the aging process through good hygiene and often to maintain autonomy until the end of life. Mental health is threatened by impairment of mental functions, depressive tendencies, and the risk of senile dementia that cannot be foreseen or avoided. It appears that keeping intellectually active and having a good level of education impact favorably on mental aging. Social health depends, for a large part, on the way society accepts and treats the elderly. They must be kept integrated into society and allowed to live at home for as long as possible. Any measures of rejection, discrimination, and exclusion should be opposed. The dignity of the elderly must be respected and activities giving them a feeling of usefulness should be encouraged. It is important to help families who care for their parents at home, to develop and evaluate healthcare networks, and encourage medical professionals and social services to work together. The change in the demographic structure of France is a considerable phenomenon requiring a long-term strategy and not only superficial and cosmetic measures.     

Extra-Cutaneous Melanin

Extra-cutaneous melanocytes derive from either the neural crest, the outer wall of the optic cup, or the cranial neural tube. Those of neural crest origin reach most bodily regions, and may give rise to primary melanoma in various tissues. The Kupffer cell produces a form of melanin, but is hardly a melanocyte. Melanocytes of the internal ear may be concerned with secretion of endolymph, trans-epithelial ion transport, and with protection against ototoxic drugs and high-intensity noise damage. There is evidence from albino animals that retinal pigment epithelium determines co-ordinates of the neural retina, and its decussation pattern during development. Neuromelanin derives from Dopamine, and is found in dopaminergic neurons widely distributed throughout the brain-stem and hypothalamus, and which project to the striatum and limbic system. Parkinsonism is due to degeneration of melanin-containing dopaminergic neurons of locus coeruleus and substantia nigra, and MPTP provides an investigative probe for studying the causes of Parkinsonism. Neuromelanin should not be regarded as a waste-product, but as something which can affect the firing properties of neurons with specific functional effect.     

Melanin and HIV in sub-Saharan Africa

HIV is common in sub-Saharan Africa. Sexually transmitted bacterial and fungal infections increase the chance of HIV infection. Melanin can prevent the penetration of skin and mucus membranes by microorganisms, and soluble melanin can inhibit HIV replication. We suggest that melanin may reduce the incidence of HIV infection through venereally acquired skin lesions, thus reducing the risk of sero-conversion and slow the progress to AIDS. Indigenous sub-Saharan peoples are highly melanized, but there is pigment variation between populations. We show that skin reflectance, a negative correlate of melanin, is positively associated with adult rate of HIV in sub-Saharan countries. There is no such relationship in populations outside sub-Saharan Africa. We suggest that melanin concentration in black people may correlate with resistance to HIV infection.     

Melanin and virulence in Cryptococcus neoformans

Melanin synthesis has been associated with virulence for the human pathogenic fungus Cryptococcus neoformans. Recent evidence indicates that C. neoformans cells synthesize melanin during infection and that this pigment protects the fungus against immune defense mechanisms.     

Melanin concentrating hormone (MCH): synthesis and bioactivity studies of MCH fragment analogues

Nineteen analogues of melanin concentrating hormone (MCH) were synthesized and tested for their skin-lightening activities in the in vitro eel skin (Synbranchus marmoratus) bioassay. All the analogues synthesized were fragments of the native sequence: Asp-Thr-Met-Arg-Cys-Met-Val-Gly-Arg-Val-Tyr-Arg-Pro-Cys-Trp-Glu-Val with sequential elimination of substituents from both the carboxy- and amino-termini. All the analogues that contained tryptophan in position 15 were found to be full agonists and equipotent to MCH. In the absence of Trp15, full agonist activity was maintained but potency was reduced ten-fold or more. The minimal fragment analogue possessing equipotency to the parent peptide, MCH, was the MCH(5-15) sequence. These observations coupled with results from work reported previously by our laboratories suggest the importance of the Trp15 residue for interaction with the MCH receptor in this assay system.     

The medical aspects of civil defense in California

Medical care for persons injured in atomic bomb attack or other far-reaching enemy action occupies an important place in civil defense plans that have been set up in California. Preparations have been made on the basis of suppositions as to where attacks might occur and estimates of the number of casualties. State and federal funds have been allocated for aid station equipment, antibiotics, plasma, blankets and litters. In the table of organization, use of all physicians, nurses and hospitals in the state is contemplated. Communities at the center of attacks would borrow facilities and medical personnel from areas not directly affected.County medical societies in California have appointed civil defense committees to work out local plans. Each physician has a part in these plans. If he does not know what his assignment is, be ought to get in touch with his county medical society headquarters immediately.     

Melanin Biosynthesis in Cryptococcus neoformans

Pigment production by Cryptococcus neoformans is virulence associated. Dopamine- and 3,4-dihydroxyphenylalanine–melanin products were identified after acidic permanganate oxidation, alkaline hydrogen peroxide oxidation, or hydrolysis with hydriodic acid. These data provide direct chemical evidence for the formation of eumelanin polymers by catecholamine oxidation by laccase alone followed by oxidative coupling of dihydroxyindole.     

Interaction Between Chemicals and Melanin

Various drugs and other chemicals, such as organic amines, metals, polycyclic aromatic hydrocarbons, etc., are bound to melanin and retained in pigmented tissues for long periods. The physiological significance of the binding is not evident, but it has been suggested that the melanin protects the pigmented cells and adjacent tissues by adsorbing potentially harmful substances, which then are slowly released in nontoxic concentrations. Long-term exposure, on the other hand, may build up high levels of noxious chemicals, stored on the melanin, which ultimately may cause degeneration in the melanin-containing cells, and secondary lesions in surrounding tissues. In the eye, e.g., and in the inner ear, the pigmented cells are located close to the receptor cells, and melanin binding may be an important factor in the development of some ocular and inner ear lesions. In the brain, neuromelanin is present in nerve cells in the extrapyramidal system, and the melanin affinity of certain neurotoxic agents may be involved in the development of parkinsonism, and possibly tardive dyskinesia. In recent years, various carcinogenic compounds have been found to accumulate selectively in the pigment cells of experimental animals, and there are many indications of a connection between the melanin affinity of these agents and the induction of malignant melanoma.