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Biomedical subjects

K Jimbow

Publications and source records attributed to K Jimbow.

At least 181 records · Page 10Linked to original sources

Immunochemical characterization of murine B16 melanoma-associated antigens and their detection in sera of tumor-bearing hosts by radioimmunoassay.

Radioimmunoassay, using radiolabeled melanoma-associated antigens (MAA), rabbit anti-B16 melanoma serum and Staphylococcus aureus Cowan I, was developed for the detection of MAA in tumor tissues as well as in sera of B16 melanoma-bearing C57BL/6 mice. MAA were partially purified from 3 M KC1 extract of murine B16 melanoma tissue by affinity column chromatography using anti-B16 serum and concanavalin A. The content of MAA was high in B16 melanoma extract, much less in allogeneic Harding Passey melanoma, and very small in fetal and normal tissues including skin and brain. The amount of circulating MAA released from the tumor into the blood of B16 tumor-bearing C57BL-6 mice was linearly proportional to the size (cube root of weight) of the growing tumor, providing a rational basis for immunodiagnosis of malignant melanoma. Immunochemical data suggest that MAA which are extractable with 3M KC1 from B16 melanoma are glycoproteins with molecular weights of 54,000, 68,000 and 94,000 daltons.

Animals↗

Comparison of eumelanogenesis and pheomelanogenesis in retinal and follicular melanocytes; role of vesiculo-globular bodies in melanosome differentiation.

Vesiculo-globular bodies, 40 nm in diameter, are present in melanosomes. The mode of their involvement in melanosomal differentiation was studied by ultrastructural comparison of eu- and pheomelanogenesis occurring in retinal and follicular melanocytes. We found that the number and distribution of these bodies differ significantly with types of melanogenesis and tissues. They were not affected by physical stimuli nor by embryonic origin of melanocytes. The earliest form of melanosomes is identical in eu- and pheomelanogenesis. The vesiculo-globular bodies are involved in organization of melanosomal constituents. In eumelanogenesis, they are more numerous in feather than in retina and hair. They are least numerous in white hair and pink eyes where melanization is blocked. During melanosomal development, they become associated with melanosomal inner lamellae and their outer surface becomes melanized, but their core is hardly melanized, thus leaving small vesicular structures. In pheomelanogenesis, their number is almost equal in feather and hair. Lamellae are not formed, but these bodies fuse with each other to form an amorphous matrix on complete differentiation of melanosomes.

Animals↗

Some aspects of melanin biology: 1950-1975.

Recent advances in the biology of mammalian pigmentation are reviewed. The multicellular epidermal melanin unit (melanocyte and associated pool of keratinocytes) rather than the melanocyte alone forms the focal point for melanin metabolism within mammalian epidermis. Within an epidermal melanin unit, melanosomes are synthesized by melanocytes and transferred to keratinocytes where they are degraded as they ascend to the epidermal surface. During the past 25 years, technical advances in biology and biochemistry have frosted a multidisciplinary approach to research on mammalian pigmentation. Emphasizing this perspective, we have examined the current state of knowledge of the form and function of epidermal melanin units from the levels of biologic organization ranging from the molecules relevant to melanin synthesis through the skin as a totally intergrated system. To an unusual degree, advances in melanin pigmentation have resulted from the integration of clinical medicine and basic science.

Animals↗

The physicochemical properties of hair in the BIDS syndrome.

The physicochemical properties of hair from a new recessive syndrome associated with brittle hair, intellectual impairment, decreased fertility, and short stature have been studied. Electrophoresis of the SCM-structural proteins showed that the alpha polypeptides appeared normal, but the matrix component was markedly reduced. This was confirmed by finding a normal alpha X-ray diffraction pattern but a reduced 1/2 cystine content of hair and an abnormal stress-strain curve. Electron-microscopic studies revealed extreme disorganization of the filaments which most likely resulted from the absence of normal cross-linking. Nails, which contain structural proteins similar to hair, also showed the abnormality. Since the matrix component seen by electrophoresis consists of more than one component the defect cannot be explained as a single structural gene abnormality.

Amino Acids↗

Role of light in human skin color viariation.

The major source of color in human skin derives from the presence within the epidermis of specialized melanin-bearing organelles, the melanosomes. Tanning of human skin on exposure to ultraviolet light results from increased amounts of melanin within the epidermis. Melanosomes synthesized by melanocytes are acquired by keratinocytes and transported within them to the epidermal surface. In some cases, the melanosomes are catobolized en route. New information indicates that the multicellular epidermal melanin unit (melanocyte and associated pool of keratinocytes) rather than the melanocyte alone is the focal point for the control of melanin metabolism within mammalian epidermis. Gross human skin color derives from the visual impact of the summed melanin pigmentation of the many epidermal melanin units. In theory, constitutive skin color in man designates the genetically-determined levels of melanin pigmentation developed in the absence of exposure to solar radiation or other environmental influences; facultative skin color or "tan" characterizes the increases in melanin pigmentation above the constitutive level induced by ultraviolet light. The details of genetic regulation of pigment metabolism within the epidermal melanin units are being clarified. In some mammals at least, the function of epidermal melanin units is significantly influenced by hormones which may be regulated by radiations received through the eyes. Based on an evolutionary history of the human family which exceeds ten million years, it is proposed that melanin pigmentation may have played a number of roles in human adaptions to changing biologic and physical environments.

Animals↗

Changes in distribution pattern of cytoplasmic filaments in human melanocytes during ultraviolet-mediated melanin pigmentation. The role of the 100-Angstrom filaments in the elongation of melanocytic dendrites and in the movement and transfer of melanosomes.

Human melanocytes characteristically contain 100-A filaments. These 100-A filaments shift from the perinuclear area to the center of the dendritic processes and are in close association with melanosomes during the different stages of UV-mediated melanin pigmentation. We suggest that these 100-A filaments in human melanocytes participate in the elongation of the dendrites and in the transfer of melanosomes.

Buttocks↗

Mitotic activity in non-neoplastic melanocytes in vivo as determined by histochemical, autoradiographic, and electron microscope studies.

Mitotic figures were demonstrated in the differentiated melanocytes of normal epidermal and nonepidermal tissues without the presence of external stimuli. These dividine melanocytes were present in human and mouse skin, mouse hair, chick feathers, and embryonic chick retinal pigment epithelium. In normal adult human epidermis, dividing melanocytes, though rare, were found in the nonstimulated areas. L-3,4-dihydroxyphenylalanine reaction on the melanocytes during mitosis demonstrated activity of the melanin-forming enzyme, tyrosinase, and ultrastructural studies demonstrated the characteristic melanosomes in variour stages of maturation. Other ultrastructural characteristics of the melanocytes during mitosis, except for the Golgi apparatus, which was smaller and less complex, were similar to those seen in well-differentiated nondividing melanocytes. Autoradiographic studies of thymidine incorporation into mouse skin indicated that 0.7% of epidermal melanocytes, when slightly stimulated, are in the S phase. Thus, in vivo differentiation of non-neoplastic melanocytes (to produce pyrosinase and melanosomes) does not preclude their replication by mitotic division.

Animals↗

Congenital circumscribed hypomelanosis: a characterization based on electron microscopic study of tuberous sclerosis, nevus depigmentosus, and piebaldism.

Subcellular defects of hypomelanosis in tuberous sclerosis (TS) (28 subjects) were compared by light and electron microscopy with oThere forms of congenital circumscribed hypomelanosis that occur in nevus depigmentosus (ND) (8 subjects) and in piebaldism (PB) (4 subjects), respectively. On the light microscopic level in both TS and ND, the population density of functioning melanocytes was normal but each perikaryon was small, and dopa activity was decreased. On the ultrastructural level, the hypomelanotic skin and hair of TS were associated with a decrease in the synthesis, melanization, and size of melanosomes; the decrease in the size of melanosomes resulted in the aggregation of melanosomes (i.e., a melanosome complex) in the keratinocytes in all the specimens examined. In ND, ther were no obvious changes in the size and melanocytes. the hypomelanosis of ND is related to the decreased synthesis and also, perhaps, abnormal transfer of melanosomes. In PB the hypomelanosis of the skin and hair results from the absence of functional melanocytes. The hypermelanotic areas of PB, however, characteristically contain melanocytes that synthesize abnormal (sperical and granular) as well as normal (ellipsoidal and lamellar) melanosomes.

Adolescent↗

Tyrosinase-mediated inhibition of in vitro leucine incorporation into mouse melanoma by 4-isopropylcatechol.

The effect of 4-isopropylcatechol (4-IPC), a potent, irreversible cutaneous depigmenting agent, on protein biosynthesis of malignant melanoma cells in mice was studied by examining the in vitro amino acid (leucine) incorporation into a microsome fraction in cell sap. The present study revealed that 4-IPC does not inhibit the protein biosynthesis of the cell-free system in mouse liver, but remarkably inhibits it in mouse melanoma cells, which contain a high level of tyrosinase. The enhanced inhibition was found also in the mouse liver cell-free system when tyrosinase was added. Air oxidation products of 4-IPC were not responsible for such inhibition. These results may indicate that 4-IPC directly inhibits protein biosynthesis, probably by some intermediates that occur in an early stage of enzymatic oxidation of 4-IPC.

Animals↗