Search PubMed⌕ Search

Biomedical subjects

K Jimbow

Publications and source records attributed to K Jimbow.

At least 109 records · Page 6Linked to original sources
PubMed1989

Acute graft-vs-host disease in an immunodeficient newborn possibly due to cytomegalovirus infection.

Acute graft-vs-host disease occurring during the early weeks of life has been previously reported as a rare disease entity. We report a case of acute graft-vs-host disease in a female infant with an immunodeficiency that was thought to be secondary to intrauterine or neonatal cytomegalovirus infection or, less likely, to a severe combined immunodeficiency. The patient presented with a triad of failure to thrive, diarrhea, and maculopapular and petechial rash. The first clue to diagnosis was the skin biopsy finding of an epidermal lymphocytic infiltrate in association with individual necrotic keratinocytes. The diagnosis was confirmed at autopsy. In the absence of an obvious graft, the disease is believed to have been the result of maternofetal T-cell transfer in utero or at delivery.

Cytomegalovirus Infections↗
PubMed1988

Specification and use of a mouse monoclonal antibody raised against melanosomes for the histopathologic diagnosis of amelanotic malignant melanoma.

The positive reactivity and specificity of a mouse monoclonal antibody (MoAb) human melanosome-specific antigen (HMSA) 2 raised against the melanosomal protein with amelanotic malignant melanoma on routine paraffin sections is reported. MoAb HMSA-2 identified cytoplasmic antigen with the following specifications: (1) a sharp heterogeneous expression in melanoma cells (acral lentiginous melanoma [ALM], 11 of 14; superficial spreading melanoma [SSM], 13 of 14; nodular melanoma [NM], one of three; and lentigo maligna melanoma [LMM], zero of two), whereas a diffuse homogeneous expression in cells of benign pigmented melanocytic nevi; and (2) an intense expression on amelanotic melanoma cells as opposed to a weak or negative expression on highly melanotic cells. The positive reactivity of MoAb HMSA-2 with amelanotic melanomas was exemplified by two shave-biopsy specimens of amelanotic subungual and plantar lesions, and by two cases of axillary and cervical amelanotic nodes that were left undiagnosed on routine hematoxylin and eosin (H & E) sections because of lack of melanin pigments. These were found, after diagnosis with MoAb HMSA-2, to possess the regressed primary lesions (both ALM).

Antibodies, Monoclonal↗
PubMed1988

Incorporation of sulfhydryl compounds into melanins in vitro.

Cysteine is known to be involved in pheomelanin synthesis. Available evidence, however, indicates that glutathione may also play an important role in melanogenesis. This in vitro study clarifies how cysteine and glutathione participate in melanogenesis. Melanins were prepared by tyrosinase oxidation of 3,4-dihydroxyphenylalanine (dopa) with various amounts of cysteine or glutathione, and were subjected to HCl hydrolysis. Synthetic melanins and the hydrolyzed melanins gave N/S molar ratios corresponding to those calculated from the ratio of dopa to cysteine or glutathione. On hydriodic acid hydrolysis, dopa plus cysteine-melanins and dopa plus glutathione-melanins gave aminohydroxyphenylalanine and cysteine, respectively, the yields of which were proportional to the sulfur content. The results indicate that cysteine is integrated into benzothiazine units (pheomelanins) while glutathione is connected to dihydroxyindole units (eumelanins) with the retention of glutathione moiety. Analysis of natural melanins, prepared by HCl hydrolysis of Sepia, B16, and Harding-Passey melanosomes, indicates that sulfur (0.4-1.4%) in these natural melanins may be derived artificially from the reaction of melanins with cysteine or cystine in the course of HCl hydrolysis.

Animals↗
PubMed1988

Immunoelectron microscopic demonstration of human melanosome associated antigens (HMSA) on melanoma cells: comparison with tyrosinase distribution.

Previously, we have developed a mouse monoclonal antibody (MoAb) HMSA-1 (human melanosome-associated antigen-1) against the melanosome fraction of human malignant melanoma, and demonstrated the selective distribution of the HMSA-1 in neoplastic melanocytes on routine paraffin sections. This study examined, by using enzyme linked immunosorbent assay (ELISA) and immunoelectron microscopy, the subcellular distribution of the HMSA-1 in malignant melanocytes. Fractionation of cell organelles and ELISA assay indicated that the HMSA-1 is rich in fractions of large granule, melanosome and endoplasmic reticulum (ER) in melanoma cells. Immunoelectron microscopic study showed that the HMSA-1 is localized in the melanosomes of various developmental stages and vacuolar structures, which appeared to be the stage I melanosomes and which contained the matrix protein. Dopa cytochemistry revealed that the distribution of MoAb HMSA-1 reaction product is localized in the area different from that of tyrosinase, indicating that the synthetic processes of melanosomal matrix protein and tyrosinase are different. Furthermore, the reaction product with MoAb HMSA-1 was seen in the rough ER, indicating that the melanosomal matrix protein is synthesized by membrane-bound ribosomes and processed through the channel of ER.

Antibodies, Monoclonal↗
PubMed1988

Positive reactivity of dysplastic melanocytes with a monoclonal antibody against melanoma melanosomes, MoAb HMSA-2.

A mouse-mouse monoclonal antibody, MoAb HMSA-2, was raised against the melanosomal protein of human malignant melanoma. To characterize the nature of dysplastic melanocytic nevi (DMN), we examined the reactivity of DMN with MoAb HMSA-2 in comparison to that of superficial spreading melanoma (SSM) and common melanocytic nevi (CMN) including junctional melanocytic nevi (JMN) on routine paraffin sections. MoAb HMSA-2 showed several unique immunohistochemical findings: a) MoAb HMSA-2 reacted with melanocytes of DMN in both the epidermis and the dermis, including the pigment granules in the keratinocytes; b) the pigment granules in the keratinocytes of DMN were found to be immature melanosomes transferred from dysplastic melanocytes to keratinocytes; c) the reactivity of epidermal melanocytes in DMN and SSM was stronger than that of junctional component in CMN, though SSM revealed a much stronger reaction than DMN; and d) keratinocytes, especially in a "shoulder" lesion of DMN which was associated with dermal lymphocytic infiltrates, often showed a strong reactivity with MoAb HMSA-2. Thus our study suggested a unique immunohistochemical feature of DMN with deranged melanogenesis as indicated by the reactivity with MoAb HMSA-2.

Animals↗
PubMed1988

Nature and biosynthesis of structural matrix protein in melanosomes: melanosomal structural protein as differentiation antigen for neoplastic melanocytes.

Two major classes of protein, i.e., structural matrix and enzymic, exist in the melanosome. In normal melanocytes, synthesis of these two components is under a strict genetic control with regulatory steps associated with transcription and translation coded with appropriate pigment genes. In abnormal neoplastic melanocytes, they become markedly aberrant. The aberrant melanogenesis can be typically manifested by an abnormality in fine structure of the melanosome. The fine structural heterogeneity of the melanosome can often be diagnostic to certain forms of malignant melanoma and dysplastic melanocytic nevus. This study brings about the importance of the structural matrix protein for the expression of fine structural heterogeneity in the melanosome by developing the 2 monoclonal antibodies, MoAb HMSA-1 and HMSA-2. The 2 MoAbs recognized the cytoplasmic antigen on paraffin embedded sections, which under immunoelectron microscopy and cell fractionation studies, were found to be localization the melanosome and smooth ER, but not Golgi complex and coated vesicles as seen in the tyrosinase studies. It is indicated (a) that the sites of the synthesis for the melanosomal protein and tyrosinase are different, (b) that the melanosomal structural protein is accumulated in the dilated vacuole of smooth ER from which the stage I melanosome is synthesized, (c) that the synthesis of melanosomal protein becomes markedly aberrant and directly reflects the abnormal fine structure of the melanosome and (d) the heterogeneity in synthesis of melanosomal protein as expressed by MoAb HMSA-1 and HMSA-2 is a useful adjunct for immunohistopathological differentiation of malignant melanoma cells from benign nevoid cells and normal melanocytes.

Antigens, Differentiation↗
PubMed1988

Scar and keloidlike lesions in progeria. An electron-microscopic and immunohistochemical study.

We describe a case of progeria with an unusual skin manifestation of numerous hyperplastic scars or keloidlike nodules on the upper and lower extremities. Electron-microscopic and immunohistochemical studies indicated that the nodules consisted of various forms of collagen tissues, including type IV collagen, and that they were surrounded by la+ cells. Approximately 60% of the la+ cellular infiltrates were Leu 1+4+, OKT9+, and functioning T cells, which were often closely apposed to fibroblasts. It is suggested that progeria is associated with hyperplastic scars or keloidlike lesions with an unusual accumulation of type IV collagen, which may be formed through interaction between activated T cells and fibroblasts after minor traumas.

Biopsy↗
PubMed1987

Mechanism of selective toxicity of 4-S-cysteinylphenol and 4-S-cysteaminylphenol to melanocytes.

Our previous studies showed that 4-S-cysteinylphenol (4-S-CP) and 4-S-cysteaminylphenol (4-S-CAP) inhibit the growth of malignant melanoma and cause depigmentation of black skin. In this study we examined kinetic constants of CP and CAP as substrates for tyrosinases and their properties as sulphydryl scavengers. 4-S-CP and 4-S-CAP were found to be much better substrates for mushroom tyrosinase than L-tyrosine while their 2-S isomers were not the substrates. 4-S-CP and 4-S-CAP were also good substrates for mammalian tyrosinase. Upon tyrosinase oxidation the two phenols conjugated with cysteine to form the cysteinyl derivatives of the corresponding catechols via o-quinone forms. The tyrosinase oxidation product of 4-S-CP had a poor ability to conjugate with alcohol dehydrogenase, a sulphydryl enzyme, while that of 4-S-CAP had a much higher ability. These results suggest that in melanocytes these phenols are oxidised by tyrosinase to the corresponding o-quinone forms, some of which conjugate with sulphydryl enzymes through cysteine residues, thus exerting cytotoxic effects.

Catechols↗
PubMed1987

Selective cytotoxicity of 4-S-cysteaminylphenol on follicular melanocytes of the black mouse: rational basis for its application to melanoma chemotherapy.

We have previously shown that 4-S-cysteaminylphenol (4-S-CAP) causes a significant inhibition of in vivo melanoma growth. To clarify the mechanism of the in vivo antimelanoma effect, this study evaluated the cellular and subcellular changes of follicular melanocytes after s.c. administration of 4-S-CAP on the lumbar areas of black and albino mice. 4-S-CAP produced a prompt, selective swelling and lysis of melanocytes, resulting eventually in the necrosis of melanocytes and the depigmentation of black hair follicles. None of the degenerative changes were seen in melanocytes and keratinocytes of control albino follicles. Comparison of melanocytes in black and albino follicles revealed that melanin synthesis is highly active in the melanocytes of black follicles while melanin and tyrosinase synthesis is not seen in the melanocytes of albino follicles. The findings indicate that the selective melanocytotoxicity of 4-S-CAP is manifested by lysis and necrosis of cells which are actively engaged in melanin synthesis. 4-S-CAP appears to provide a new modality for rational chemotherapy of malignant melanoma.

Animals↗
PubMed1987

Development of MoAb HMSA-2 for melanosomes of human melanoma and its application to immunohistopathologic diagnosis of neoplastic melanocytes.

To characterize the biologic and molecular nature of melanosomal proteins, we recently developed two mouse monoclonal antibodies (MoAbs), human melanosome-associated antigen (HMSA)-1 and HMSA-2, for melanosomes isolated from human malignant melanoma. This study describes the methods of development for MoAb HMSA-2 and the specificity and distribution of antigen(s) reactive with it in normal and pathological tissues. Characteristically, MoAb HMSA-2 was found to detect neoplastic melanocytes on formalin-fixed and paraffin-processed specimens. The reaction patterns for benign and malignant melanocytic tumors were different, i.e., homogeneous reactivity in the dermal cells of common melanocytic nevi but heterogeneous reactivity in the same type of cells in malignant melanoma. MoAb HMSA-2 reacted positively with the epidermal melanocytes in the lesions of dysplastic melanocytic nevi, but not with those of common melanocytic nevi. Reaction products with MoAb HMSA-2 were localized in the cytoplasm. MoAb HMSA-2 did not react with normal melanocytes even on frozen sections. Benign and malignant epithelial and soft tissue tumors of the skin were usually negatively stained with MoAb HMSA-2. Findings indicate that MoAb HMSA-2 is a unique MoAb which identifies neoplastic melanocytes and which can be useful in differentiating each type of melanocytic tumor.

Antibodies, Monoclonal↗
PubMed1987

Synthesis of cysteinylphenol, cysteaminylphenol, and related compounds, and in vivo evaluation of antimelanoma effect.

Phenolic and catecholic compounds were synthesized, by combination with cysteine or cysteamine through thioether bond, and their antimelanoma and melanocytotoxic effects were evaluated. Among nine compounds tested, 4-S-cysteaminylphenol (CAP) resulted in an increase in the life span (% ILS) of melanoma-bearing mice and in the growth inhibition (% GI) of melanoma tissue. 4-S-Cysteinylphenol (CP) and its methyl ester form also showed some increase in % GI. The 2-S-isomers of CP and CAP and diphenolic derivatives of CP did not show any significant antimelanoma effect. In addition, the s.c. injection of 4-S-CAP and 4-S-CP, in particular 4-S-CAP, caused the depigmentation of black hair which was manifested by loss of functioning melanocytes, as seen under light microscopy. The 4-S-CAP appears to provide a basis for development of a new class of antimelanoma and melanocytotoxic agents that are more stable than catecholic compounds, which have been most widely utilized as a source of rational chemotherapy for malignant melanoma.

Animals↗
PubMed1987

Dysplastic melanocytic nevus. Electron-microscopic observation as a diagnostic tool.

Dysplastic melanocytic nevi (DMN) are distinctive cutaneous nevomelanocytic lesions that possess unique clinical and histopathological features. In our previous study, we showed that the fine structure of melanosomes in epidermal melanocytes of DMN are abnormal and reveal deranged melanogenesis. This study is an extension of our previous study and clarifies the fine structure of melanosomes in both epidermal melanocytes and keratinocytes with observations in an additional 10 cases of DMN with and without a marked mesenchymal response. We found that a poor mesenchymal response does not exclude fine structural abnormality of melanosomes in DMN; that abnormal melanosomes are manifested by a spherical shape with either fine granules or incompletely developed lamellae and/or both; that melanization occurs unevenly on the spherical granular and/or incompletely on the lamellar matrices; and that these abnormal melanosomes are transferred to keratinocytes before being completely melanized, and they reveal marked degradation. We suggest that the fine structural characterization of abnormal melanosomes is a new adjunct for histopathological diagnosis of DMN.

Dysplastic Nevus Syndrome↗
PubMed1987

Development of MoAb HMSA-3 and HMSA-4 against human melanoma melanosomes and their reactivities on formalin-fixed melanoma tissues.

To elucidate the nature of melanosomal protein in normal and malignant melanocytes, two mouse monoclonal antibodies (MoAbs), designated MoAb HMSA-3 and MoAb HMSA-4, were developed by the solubilized melanosomes of human malignant melanoma. The specificity of the two MoAbs was characterized immunohistochemically by comparison with that of MoAb HMSA-2 in various forms of melanoma tissues. MoAb HMSA-3 and MoAb HMSA-4 were IgM, k subclass while MoAb HMSA-2 was IgG1, k subclass. The three MoAbs possessed many similarities; (a) positive reactivity in formalin-fixed and paraffin-processed specimens, (b) identification of cytoplasmic antigen(s) in melanoma cells, (c) negative reactivity with normal epidermal melanocytes on paraffin-sections, and (d) intense reaction with amelanotic melanoma cells, particularly in superficial spreading and acral lentiginous melanoma and in metastatic lymph nodes. The three MoAbs, however, identified the different cells on the same serial sections, suggesting that the three may recognize the different epitopes. Thus in 32 cases of primary and metastatic melanomas examined, one of the three MoAbs always showed a positive reactivity, though the other two were negatively or weakly reacted. Our study indicated that the melanosomal protein may provide a unique source to develop MoAbs which identify malignant melanocytes on routine paraffin sections.

Animals↗
PubMed1987

Depigmentation of black guinea pig skin by topical application of cysteaminylphenol, cysteinylphenol, and related compounds.

Phenol and catechol were combined with sulfur to develop new melanocytotoxic agents. Among these synthetic compounds, 4-S-cysteaminylphenol (4-S-CAP) and 4-S-cysteinylphenol (4-S-CP), which showed an in vivo antimelanoma effect, were evaluated for cytotoxicity to normal epidermal melanocytes using hydroquinone (HQ) as the control. Topical application of 4-S-CAP on the skin of black guinea pigs revealed a marked depigmentation of black skin. 4-S-Cysteinylphenol also showed some depigmenting potency. 2-S-Cysteinylhydroquinone, which was made by combining cystine with HQ, on the other hand, did not show any depigmenting effect. Depigmentation of black skin by 4-S-CAP appeared to derive from: a decrease in the number of functioning melanocytes; a decrease in the number of melanosomes synthesized within the melanocytes and transferred to keratinocytes; and destruction of the membranous organelles of the melanocytes. None of these degenerative changes was observed in the keratinocytes, indicating the selective effect of 4-S-CAP on melanocytes.

Animals↗
PubMed1987

A computed image analyzing system for quantitation of melanocyte morphology in café-au-lait macules of neurofibromatosis.

Split-dopa preparation is a commonly used technique to visualize the epidermal melanocytes. It can characterize the number of melanocytes and their tyrosinase (dopa-oxidase) activities. There is not, however, any method to quantitate the morphologic changes of dopa-positive melanocytes in the split preparation. This study designed a computed image analyzing system and evaluated the structure of epidermal melanocytes in café-au-lait macules with comparison to normally pigmented skin in 5 patients with neurofibromatosis. By this method we were able to delineate the melanocyte structure with melanocyte population and coloration of the macules. We found that the population and structure of melanocytes differ greatly depending on the coloration of the café-au-lait macules. The light brown and brown macules showed the normal population of melanocytes with an increase in the area and perimeter of whole cell; the area, perimeter, and diameter of cytoplasm; and the area, length, and breadth of dendrites. In contrast, the dark brown macules revealed a significant increase of the epidermal melanocytes with a decrease in all of these parameters. Thus, the methodologic design presented here may enable a quantitative, two-dimensional analysis of melanocyte structure at the light microscopic level in the normal skin and in various pigmentary disorders.

Humans↗
PubMed1987

Dual surface makers and HTLV-I proviral DNA in a cutaneous tumour nodule in a case of adult T cell leukaemia/lymphoma.

The phenotypic and morphological profiles of atypical cells in a case of adult T cell leukaemia/lymphoma were studied using a panel of monoclonal antibodies and electron microscopy. Retroviral sequence restriction analysis showed the presence of human T cell leukaemia/lymphoma virus type I (HTLV-I) in the skin lesion. Our case showed several unique features in the clinical, haematological, histopathological and immunohistochemical findings. An erythematous plaque and tumour nodules in the skin were found without any abnormal lymphocytes such as flower cells in the peripheral blood and bone marrow HTLV-I proviral DNA was detected in the skin tumour cells but not in the peripheral blood lymphocytes, and in the tumour nodule, atypical cells showed a distinct difference in morphology between cerebriform cells in the upper dermis and large lymphoid cells in the lower dermis. The cerebriform cells had, immunohistochemically, a T helper/inducer (Th/i) phenotype whereas the large lymphoblastoid cells possessed both the Th/i and T suppressor/cytotoxic (Ts/c) phenotypes. Ki-I antigen was detected in the large lymphoblastoid cells, but not in the cerebriform cells.

Adult↗
PubMed1987

Association of vesiculobullous eruptions with mycosis fungoides.

Mycosis fungoides (MF) is, on extremely rare occasions, associated with vesiculobullous eruptions. This report describes clinical, histological and immunohistochemical findings of a case of MF with vesiculobullous lesions. Characteristic features of our case included: bullous lesions evolving rapidly in 12-24 h with severe itch on erythematous and normal-appearing skin; a positive Nikolsky sign; an intraepidermal blister; direct and indirect immunofluorescence stainings were all negative with IgG, IgA, IgM and C3, and atypical lymphocytes in the infiltrates were of helper/inducer T cell type.

Blister↗