Search PubMed⌕ Search

Biomedical subjects

K Jimbow

Publications and source records attributed to K Jimbow.

At least 145 records · Page 8Linked to original sources

"Total" acidic metabolites of catecholamines in urine as determined by hydrolysis with hydriodic acid and liquid chromatography: application to patients with neuroblastoma and melanoma.

We describe a method for determining the "total" excretion of acidic metabolites of catecholamines by measuring 3,4-dihydroxyphenylacetic acid (DOPAC) formed by hydriodic acid hydrolysis of 4-hydroxy-3-methoxyphenylacetic acid (HVA), 4-hydroxy-3-methoxymandelic acid (VMA), and their conjugates. The DOPAC in the diluted hydrolysate is measured directly by liquid chromatography with electrochemical detection. Normal values, expressed in relation to excretion of creatinine, vary as a function of age. For healthy subjects, the mean DOPAC value after hydrolysis was 1.15 times that for unconjugated HVA, VMA, and DOPAC combined. Preliminary results for patients with neuroblastoma and melanoma indicate the potential usefulness of the method for diagnosis and prognosis of patients with neural crest tumors that produce dopa or catecholamines.

3,4-Dihydroxyphenylacetic Acid↗

Ultrasonic comparison of two morphologically distinct melanosomes in malignant melanomas.

Ultrasonic measurement (0.333-200 MHz) of melanosomes isolated from B16 and Harding Passey (HP) mouse melanomas indicates that the partial wave resonance and principal relaxation of the 2 kinds of melanosomes are similar, but that their stochastic resonance is markedly different. The structure of the melanosomes appears basically amorphous, but linearly ordered and copolymeric in the molecular dimension of a segment composed of 5-6 zigzag units, which are packed closely in B16 and more openly in HP.

Animals↗

Characterization of melanogenesis in mouse and guinea pig hair by chemical analysis of melanins and of free and bound dopa and 5-S-cysteinyldopa.

This study examined how various genotypes of coat color in mice and guinea pigs are related to the type and content of melanin and to the levels of free and protein-bound dopa and 5-S-cysteinyldopa in hair. In analysis of black, yellow, and white areas of tortoiseshell guinea pigs, the melanogenesis type was in parallel to the type and content of melanin and was correlated fairly well with the levels of melanin precursors. In mouse hair, substitution of the brown allele (bb) for black (BB) reduced the eumelanin content to 1/2 to 1/3, while it significantly increased the dopa level. The dilution (dd) gene of mice reduced the eumelanin content only slightly, while the gene for pink-eyed dilution (pp) reduced the content of eumelanin and the level of dopa to as much as 1/10. From the eumelanin/pheomelanin ratio, the melanin of brown and dilute brown mice was found to be eumelanic, while the melanin of pink-eyed dilution mice appeared to be a mixed type because of an extremely low content of eumelanin. The levels of bound dopa and 5-S-cysteinyldopa in hair were found to largely reflect the tyrosinase activity.

Animals↗

Characterization of melanogenesis and morphogenesis of melanosomes by physicochemical properties of melanin and melanosomes in malignant melanoma.

This study elucidates the nature of melanogenesis in B16 and Harding-Passey (HP) mouse melanomas producing melanin and melanosomes of different color and fine structure, i.e., brown-black eumelanosome-like B16 granules and reddish brown pheomelanosome-like HP granules, and compares them with "typical" 3,4-dihydroxyphenylalanine (DOPA) and sepia eumelanins and sepia eumelanosomes. The melanin content of B16 melanosomes was more than three times higher than that of HP melanosomes. The content of free and protein-bound DOPA and 5-S-cysteinyldopa varied greatly in B16, HP, and sepia melanosomes and was unrelated to melanin content. Chemical analysis of the eumelanin: pheomelanin ratio in melanosomes and elemental analysis of isolated melanin showed that B16 and HP melanins are primarily eumelanic, with a higher ratio of pheomelanic component in HP melanin. The spectra of electron spin resonance and IR and X-ray small-angle scattering of B16 and HP melanins were basically similar to those of sepia and DOPA melanins. B16, HP, and DOPA melanins were dissolved in aqueous NH3, while sepia melanin was dissolved to a far lesser extent. It was concluded that both B16 and HP melanomas are primarily involved in eumelanogenesis, although the fine structure of their melanosomes is entirely different, and that the marked color difference in the two melanosomes is related to a difference in the absolute content of eumelanin, the presence of a small amount of pheomelanin, and the mode of chemical bindings of melanin to structural proteins. In contrast to normal skin and hair, melanosome morphogenesis may not directly correspond to melanogenesis type in malignant melanoma.

Animals↗

[Utilization of melanin precursors for experimental chemotherapy of malignant melanoma].

Melanin synthesis is a metabolic pathway unique and specific to melanocytes. It occurs by conversion of tyrosine to dopa and dopaquinone in the presence of tyrosinase. It is highly accelerated in malignant melanoma with a marked increase of tyrosinase activity. This study summarizes the recent progress in experimental chemotherapeutic approaches to malignant melanoma by utilizing melanin precursors, and presents our current results. Our studies indicated (a) that hydroquinone and 4-isopropylcatechol are selectively toxic to melanocytes and melanoma cells, (b) that their actions are mediated through tyrosinase, and (c) that dopa is selectively and highly incorporated into melanoma cells and melanocytes depending on the tyrosinase activity. In addition, our new compounds, i.e., 4-S-cysteinylphenol and 4-S-cysteaminylphenol were highly toxic to melanoma cells, increasing the life span of B16 melanoma bearing mice and decreasing melanoma growth in C57 BL mice. Other synthetic compounds, e.g., cysteinylcatechols and their devivatives, were, however, not toxic to melanoma cells. 4-S-cysteinylphenol and 4-S-cysteaminylphenol appeared to exert their cytotoxicity through the action of tyrosinase present in melanoma cells, thus providing a kind of "guided missile" approach to melanoma chemotherapy.

Animals↗

Ultrasonic measurement of melanosomes for characterization of their physicochemical structure in B16 and Harding-Passey melanomas.

Ultrasonic measurement of the two different forms of melanosomes was carried out at 20 to 300 MHz on B16 and Harding-Passey mouse melanomas which produce ellipsoidal-lamellar and spherical-granular melanosomes, respectively. We found that the structure of the two forms is basically amorphous and copolymeric in the molecular dimension of a segment composed of 5 to 6 zigzag units. A marked difference in particle wave resonance was found around 200 MHz in the two melanosomes. Based on the chemical structure of melanin proposed by Hempel, it was indicated that the physical structure of Harding-Passey melanosomes is a copolymer in which melanin and protein moieties run parallel to each other but may bind together at the sites of planar groups, while that of B16 melanosomes is a double-helix polymer of melanin and protein moieties with a screw symmetry of N = 6. This type of one-dimensional cyclic ordering, commonly known as the Born-Karman periodic boundary condition in semiconductive band theory, may be related to the formation of the lamellar structure seen in B16 melanosomes.

Animals↗

[Control of multiple skin and lung metastasis of malignant melanoma by combined DAV and OK-432 chemoimmunotherapy in association with large-scale administration of indomethacin].

Skin metastasis of malignant melanoma has been difficult to control by chemoimmunotherapy. We report a case of melanoma with marked reduction of multiple skin and lung metastasis and an improved cell-mediated immunity using combined DAV (DTIC, ACNU, Vincristine) and OK-432 chemoimmunotherapy in association with doses of indomethacin administered over a long period (250 mg/day, 6 months) to relieve the cancerous pain.

Aged↗

Biological behavior and natural course of acral malignant melanoma. Clinical and histologic features and prognosis of palmoplantar, subungual, and other acral malignant melanomas.

This study, based on 67 Japanese cases of acral malignant melanomas, presents their gross clinical and histologic features and the natural history of the lesions with respect to anatomic locations, thicknesses, and sex of patients afflicted. We found that the anatomic locations of malignant melanomas in Japanese are unique in the sense that more than 40% of cutaneous melanomas occurred in palmoplantar and subungual sites, about 80% showed the clinical and histologic features of the acral lentiginous type, 15% were in the form of nodular malignant melanoma, and 3% in the form of superficial spreading malignant melanoma. We did not find any difference in prognosis of acral malignant melanomas from that of malignant melanomas on other parts of the body. Neither was there significant difference in the overall survival rates or in the survival rates within same range of thickness. There was some difference in the survival rates of patients with palmoplantar and subungual malignant melanoma of men and women, the women being younger and having better survival rates than the men. However, no significant difference was found in survival rates from the factor of thickness of lesion. Our study indicates the usefulness of specifications of thickness and anatomic site in predicting biological behavior and natural course of acral malignant melanomas.

Aged↗

[Malignant melanoma in Japan: unique distribution and effect of DAV chemoimmunotherapy (part II)].

This study, based on a cooperative group project involving 4 major medical institutes in Japan, presents the second survey of malignant melanoma patients (198 cases) where an attempt is made to systemically evaluate the survival rates of these patients with respect to the tumor thickness and location of primary lesions, and the response to chemoimmunotherapy. More than 50% of total collected cases showed the primary lesions on the limbs. The most common type and site of involvement is the acral lentiginous melanomas involving the plantar areas (more than 30). The survival rates affecting the limbs were better than those affecting the non-limb areas. However, the comparison of the survival rates did not reveal any difference between those cases affecting the plantar and non-plantar areas. The difference in the prognosis of melanoma patients appeared to be related to the tumor thickness. By historical comparison, the DAV (DTIC, ACNU, VCR) treated group exhibited a better survival rate than the non-DAV treated group. Furthermore, the DAV group with immunoadjuvant therapy (mainly OK-432) showed a better prognosis than the DAV group without any immunoadjuvant therapy.

Adolescent↗

[Local application of interferon beta to skin lesions of malignant melanoma and malignant lymphoma--clinical and histopathological analysis].

Interferon (IFN) beta was applied locally to skin lesions of malignant melanoma (MM: 3 cases in stage IV and 1 case in stage II) and malignant lymphoma (ML: 3 cases of mycosis fungoides in stages II-III and 1 case of primary cutaneous lymphoma in stage III). It was found that IFN beta was remarkably effective for ML (3 in CR and 1 in PR), but far less effective for MM (3 in PD and 1 in NC). Biopsy specimens of clinically regressed areas revealed histopathology entirely different from each other, skin lesion of MM being infiltrated by numerous inflammatory cells such as lymphocytes and macrophages, whereas that of ML infiltrated Least. Local application of IFN beta appears to provide a new modality for treatment of cutaneous ML, which has the primary lesions on skin and has been hardly controlled by systemic chemoimmunotherapy.

Aged↗

Combined chemical and electron microscopic studies of pheomelanosomes in human red hair.

This study clarified the fine structure of pheomelanosomes in human red hair by quantifying the contents of pheomelanin and eumelanin and by identifying the fine structure of melanocytes and melanosomes based on their melanogenesis type in follicles. Out of 5 red-haired subjects, 3 were found to exhibit pheomelanogenesis in follicles, while the remaining 2 were found to have a mixed type melanogenesis of pheomelanin and eumelanin. Melanocytes in the pheomelanic follicles contained spherical melanosomes which revealed sequences of development identical to those seen in the pheomelanosomes of mice and guinea pigs. In contrast, the follicles of mixed type melanogenesis contained 2 different populations of melanocytes, i.e., one with synthesis of spherical melanosomes such as seen in the pheomelanic follicles and the other with synthesis of ellipsoidal-lamellar (filamentous) granules of eumelanosome form. It was concluded that (a) visual differentiation of hair color does not always reflect the melanogenesis type in human red hair, (b) chemical analysis of melanogenesis type corresponds well to the fine structural differentiation of eumelanosomes and pheomelanosomes, and (c) human pheomelanosomes are spherical granules with microvesicular (vesiculoglobular) and proteinaceous matrices on which melanin deposition is spotty and granular.

Adult↗

Characterization of structural properties for morphologic differentiation of melanosomes. III. free and protein-bound dopa and 5-S-cysteinyldopa in B16 and Harding-Passey melanomas.

This study analyzed the free and protein-bound forms of dopa, 5-S-cysteinyldopa (5-S-CD), and 5-S-glutathionedopa (5-S-GD) in B16 and Harding-Passey (HP) mouse melanomas to investigate the role of these catechols for melanogenesis and melanosome morphogenesis, inasmuch as these tumors produce melanosomes different in color and ultrastructure, i.e., eumelanosome type in B16 and pheomelanosome type in HP. Between B16 and HP mouse melanomas, however, we found (a) no significant difference in the level of free dopa and 5-S-CD in melanosomes and tumors, although the levels of these catechols reflected well the type of melanogenesis in control hair of normal mice, (b) a significant difference in free 5-S-GD level, which might, in part, reflect the observed difference in melanogenesis, and (c) no apparent difference in the level of bound dopa and 5-S-CD in either melanosomes or tumors. Thus, the striking difference in the color of melanosomes between B16 and HP melanomas seems to be related primarily to the content--not the type--of melanin pigments.

Animals↗

Quantitative analysis of eumelanin and pheomelanin in hair and melanomas.

In this study, a method is provided for analyzing quantitatively the content and the class of melanin pigments in the tissues, e.g., hair and melanoma. The method is simple and rapid because it does not require the isolation of melanins from the tissues. The rationale was that permanganate oxidation of eumelanin yields pyrrole-2,3,5-tricarboxylic acid (PTCA) as its major pyrrolic product, which may serve as a quantitatively significant indicator of eumelanin, while hydriodic acid hydrolysis of pheomelanin yields amino-hydroxyphenylalanine (AHP) as a specific indicator of pheomelanin. The degradation products, PTCA and AHP, were determined by high-performance liquid chromatography. Sepia melanosome-melanin and synthetic 5-S-cysteinyldopa-melanin served as reference standards of eumelanin and pheomelanin, respectively. Our method provided data that corresponded well to the content and class of melanins in normal hair. Based on this control study, it was found that the melanins in the melanosomes of both B16 and Harding-Passey (HP) melanomas were eumelanic and that the melanin content in B16 melanosomes was more than 10 times higher than that in HP melanosomes, though these two melanosomes revealed distinct colors and ultrastructures, i.e., brown-black, eumelanosome-like granules in B16 and reddish- or light-brown, pheomelanosome-like granules in HP.

Animals↗