Plasmacytosis: systemic or cutaneous, are they distinct?
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Aged↗
Biomedical subjects
M Komine
Publications and source records attributed to M Komine.
Eccrine syringofibroadenoma (Mascaro): an immunohistochemical study.
Eccrine syringofibroadenoma is an uncommon benign eccrine tumor, which was first described by Mascaro in 1963. It usually develops on the extremities of elderly persons. We report on a 74-year-old man who presented with a 2-year history of a slowly growing lesion on his face. A detailed histologic and immunohistochemical study was performed on the biopsy material. The tumor consisted of epidermal-derived anastomosing thin epithelial cords embedded in a fibrovascular stroma. The epithelial cords contained ductal and cystic structures lined by luminal cells, which were decorated by antibodies against carcinoembryonic antigen, keratin K19, K8, and K18. Antibody to keratin K6 decorated the luminal walls of the acrosyringia. Antibodies to filaggrin decorated the superficial luminal structures. These results suggest dual acrosyringial and dermal duct differentiation in syringofibroadenoma.
Adenofibroma↗
An open trial of oral macrolide treatment for psoriasis vulgaris.
Seventeen patients were included in a clinical open trial of macrolides for treatment of psoriasis vulgaris. PASI scores, itch and ointment scores were used to evaluate their effectiveness. PASI scores dropped from 22.8 to 13.7; this was statistically significant. Itch reduced in 11 out of 13 patients, and the extent of itch reduced significantly by 54% on average. Ointment scores reduced from 44.9 to 34.4, which was also statistically significant. Macrolides are known not only as potent anti-biotics, but also as immunomodulatory agents. These data suggest that macrolides could be used as one of the adjunctive therapies of psoriasis vulgaris, and this study is a first step toward the future evaluation of macrolides in a double blind trial.
Administration, Oral↗
Novel mechanism of steroid action in skin through glucocorticoid receptor monomers.
Glucocorticoids (GCs), important regulators of epidermal growth, differentiation, and homeostasis, are used extensively in the treatment of skin diseases. Using keratin gene expression as a paradigm of epidermal physiology and pathology, we have developed a model system to study the molecular mechanism of GCs action in skin. Here we describe a novel mechanism of suppression of transcription by the glucocorticoid receptor (GR) that represents an example of customizing a device for transcriptional regulation to target a specific group of genes within the target tissue, in our case, epidermis. We have shown that GCs repress the expression of the basal-cell-specific keratins K5 and K14 and disease-associated keratins K6, K16, and K17 but not the differentiation-specific keratins K3 and K10 or the simple epithelium-specific keratins K8, K18, and K19. We have identified the negative recognition elements (nGREs) in all five regulated keratin gene promoters. Detailed footprinting revealed that the function of nGREs is to instruct the GR to bind as four monomers. Furthermore, using cotransfection and antisense technology we have found that, unlike SRC-1 and GRIP-1, which are not involved in the GR complex that suppresses keratin genes, histone acetyltransferase and CBP are. In addition, we have found that GR, independently from GREs, blocks the induction of keratin gene expression by AP1. We conclude that GR suppresses keratin gene expression through two independent mechanisms: directly, through interactions of keratin nGREs with four GR monomers, as well as indirectly, by blocking the AP1 induction of keratin gene expression.
Gene Expression Regulation↗
[Clinical symptoms and characteristic MR spectroscopic findings in Pelizaeus-Merzbacher disease].
Clinical symptoms and MR spectroscopic findings were studied on 4 cases of Pelizaeus-Merzbacher disease including 1 autopsy case. Common symptoms were severe mental retardation and spastic tetraplegia. These cases had nystagmus, and one had involuntary athetotic movement. Genetical diagnosis revealed in 2 cases, duplication of proteolipid protein (PLP) and deletion in 1, whereas one case had no abnormality of PLP gene. MRI indicated the reversal of signal intensities on T1- and T2-weighed images, a characteristic finding of PMD MR spectroscopy demonstrated a pattern of NAA in 3 cases. This was specific to PMD because other white matter diseases show a decrease in NAA. In conclusion, MRS was useful to differentiate PMD from other white matter diseases.
Adult↗
A novel role of IL-15 in the development of osteoclasts: inability to replace its activity with IL-2.
IL-15 shares many activities with IL-2 on stimulating lymphocytes, hematopoietic progenitor cells, and macrophages. However, the role of IL-15 in osteoclastogenesis has not been elucidated. The recent finding of abundant IL-15 in rheumatoid arthritis synovial fluids suggested a possible role for this cytokine in the pathological destruction of bone and prompted us to determine whether IL-15 stimulates osteoclast formation. IL-15 stimulated the formation of multinucleated osteoclast-like cells in rat bone marrow cultures. In stroma-free cultures, IL-15 increased the number of mononuclear preosteoclast-like cells in the early stage of osteoclast formation. The stimulation was observed even after treatment with IL-15 for only 24 or 48 h of culture. Moreover, low IL-15 concentration (0.1 ng/ml) strongly increased the level of calcitonin receptor mRNA of mononuclear preosteoclast-like cells. Although IL-15 is known as a potent stimulator of TNF-alpha, its activity was not abolished by addition of anti-TNF-alpha Ab. Interestingly, IL-2 and IL-7, which utilize some IL-15R components, had no effect on osteoclast differentiation, but pretreatment with IL-2 or IL-7 of bone marrow cells before the addition of IL-15 inhibited the enhancing activity of IL-15. In summary, IL-15 has a novel activity to stimulate the differentiation of osteoclast progenitors into preosteoclasts, which cannot be replaced by IL-2 but may use components in common with IL-2R to mediate its effects.
Animals↗
The action of a novel vitamin D3 analogue, OCT, on immunomodulatory function of keratinocytes and lymphocytes.
Topical vitamin D3 has relatively recently been introduced for the treatment of psoriasis. Synthetic vitamin D3 analogues with a high potential for inducing differentiation of cells, but with a low hypercalcemic effect have recently been developed. One such synthetic analogue of 1,25-dihydroxyvitamin D3 (calcitriol), 22-oxacalcitriol (OCT), is a novel agent for the topical treatment of psoriasis. The activity of OCT in vitro was investigated and compared with that of a series of vitamin D3 analogues as to their ability to inhibit murine T lymphocyte proliferation stimulated by con-A, to suppress IL-6 and IL-8 production by keratinocytes stimulated with IL-1alpha and TNFalpha, and to inhibit AP-1- and NFkappaB-dependent reporter gene expression. OCT inhibited the proliferation of lymphocytes and suppressed IL-8 and IL-6 production by keratinocytes to the same extent as the other vitamin D3 analogues. It also inhibited AP-1- and NFkappaB-controlled luciferase activity to the same extent as the other vitamin D3 analogues, which demonstrates its mechanism of action in the suppression of inflammatory processes.
Animals↗
Epidermal signal transduction and transcription factor activation in activated keratinocytes.
In the area of biology, many laboratories around the world are dissecting and characterizing signal transduction mechanisms and transcription factors responsive to various growth factors and cytokines, in various cell types. However, because of the differences in systems used, it is not clear whether these systems coexist, whether they interact meaningfully, and what their relative roles are. Epidermal keratinocytes are the perfect cell type in which to integrate this knowledge, because in these cells these mechanisms are known to be relevant. Keratinocytes both produce and respond to growth factors and cytokines, especially in pathological conditions and during wound healing, when the physiology of keratinocytes is altered in a way specified by the presence of a subset growth factors and cytokines. In fact, growth factors and cytokines cause the major changes in gene expression and keratinocyte behavior in various cutaneous diseases. In some cases, such as in wound healing, these responses are highly beneficial; in others, such as in psoriasis, they are pathological. It is not clear at present which are operating in which conditions, which are important for the healing process and which are harmful. Growth factors and cytokines affect keratinocytes sometimes simultaneously, at other times individually. In this manuscript we describe the signal transduction pathways responsible for the effects of interferons, the EGF/TGF alpha family and the TNF alpha/IL-1 family of signaling molecules. We also describe the important transcription factors known to be functional in epidermis, with particular emphasis on those factors that are activated by growth factors and cytokines. Finally, we describe what is known about transcriptional regulation of keratin genes, especially those specifically expressed in pathological processes in the epidermis. We expect that the enhanced understanding of the pathways regulating gene expression in keratinocytes will identify the pharmacological targets, the signal transducing proteins and the corresponding transcription factors, used by growth factors and cytokines. This research will led to development of compounds precisely aimed at those targets, allowing us to isolate and inhibit the harmful side effects of growth factors and cytokines. Such compounds should lead to highly specific and therefore more effective treatments of the cutaneous disorders in which these pathways play significant roles.
Gene Expression Regulation↗
Regulation of epidermal expression of keratin K17 in inflammatory skin diseases.
Keratin K17, the myoepithelial keratin, is expressed in psoriasis but is not present in healthy skin. Psoriasis is associated with production of gamma interferon (IFN gamma), which induces the expression of keratin K17 by activating transcription factor STAT1. Our hypothesis states that the induction of K17 is specific for the inflammatory reactions associated with high levels of IFN gamma and activation of STAT1. One of the corollaries of the hypothesis is that the STAT1-activating cytokines should induce the expression of keratin K17, whereas those cytokines that work through other mechanisms should not. Furthermore, because the STAT activation pathway is dependent upon protein phosphorylation events, phosphorylation inhibitors should attenuate the induction of keratin K17, whereas protein phosphatase inhibitors should augment it. To test this hypothesis, we analyzed lesional samples of inflammatory diseases using immunofluorescence, transfected keratinocytes with K17 gene promoter DNAs in the presence of various cytokines, and followed nuclear translocation of STAT1 in keratinocytes using specific antibodies. Confirming the hypothesis, we found that K17 is induced in psoriasis and dermatitis caused by delayed type hypersensitivity, which are associated with high levels of IFN gamma, but not in samples of atopic dermatitis, which is not. Two cytokines, interleukin-6 and leukemia inhibitory factor, which can induce phosphorylation of STAT1, can also induce K17 expression, whereas interleukin-3, interleukin-4, interleukin-10, and granulocyte macrophage colony stimulating factor have no effect on K17 expression. As expected, staurosporine and genistein inhibited, whereas okadaic acid augmented, the induction of K17 by IFN gamma. Our data indicate that in inflammatory skin diseases, lymphocytes, through the cytokines they produce, differently regulate not only each other, but also keratin gene expression in epidermis one of their target tissues.
Cytokines↗
Alteration of human melanoma gangliosides by IFN-gamma, IL-2, and IL-4.
In lesions of malignant melanoma, melanoma cells are exposed to various cytokines produced by inflammatory reactions. As a result, transformation of melanoma cells is expected to occur. We studied alterations in human melanoma cell line ganglioside composition after exposing melanoma cell lines to interferon (IFN)-gamma, interleukin (IL)-2, and IL-4 by biochemical methods. IFN-gamma increases the ratio of a-series gangliosides and the ratio of GM3/GD3. This suggests an alteration of immunoreactivity, a decrease in ganglioside sialyltransferase II activity, and an decrease in the malignant character of these cells. The alteration of the ganglioside profile varied among cytokines and cell lines. The progression of malignant melanoma may be influenced by reciprocal interactions between the melanoma cells and the host immune system.
Gangliosides↗
A case of generalized pustular psoriasis followed by bullous disease: an atypical case of bullous pemphigoid or a novel bullous disease?
We describe a 31-year-old Japanese woman with generalized pustular psoriasis treated with PUVA who subsequently developed a bullous disease. Throughout the disease course, there was no phase of psoriasis vulgaris. Although several reports describe coexistence of psoriasis vulgaris and bullous disease such as bullous periphigoid, coexistence of generalized pustular psoriasis without any phase of psoriasis vulgaris and bullous disease is rare. As for the bullous disease, direct immunofluorescence study showed IgG and C3 deposition along the basement membrane zone. Indirect immunofluorescence disclosed IgG antibasement membrane zone antibodies. Indirect immunofluorescence on 1 mol/l sodium chloride-split skin demonstrated linear IgG staining almost exclusively on the dermal side of the split. Western immunoblot analysis revealed that the antibody was directed to neither epidermolysis bullosa acquisita antigen nor bullous pemphigoid antigens. Considering the unusual clinical course, we suspect the possibility of a novel autoimmune blistering disease.
Adult↗
Somatic mosaicism for a DMD gene deletion.
Mosaicism is a mixed state, with two cell populations of different genetic origins caused by a cell mutation occurring after fertilization. In the present case, DNA analysis of lymphocytes led to a DMD diagnosis before death. Postmortem immunocytochemical and DNA analysis showed somatic mosaicism. At age 18 years, blood lymphocyte DNA analysis showed a DMD gene deletion, upstream from exon 7 to the 5' end containing both muscle and brain promoters. As the patient's mother and elder sister had no deletions, he was considered to have a new mutation. Immunocytochemical studies of postmortem tissues showed that dystrophin was absent from the tongue, deltoid, intercostal, psoas and rectus femoris muscles, but there was a mix of dystrophin-positive and negative fibers in the rectus abdominis, cardiac, temporalis and sternocleidomastoid muscles. All diaphragm cells were dystrophin positive. Polymerase chain reaction (PCR) amplification from all tissues except the temporalis and sternocleidomastoid muscles, diaphragm and kidney, in which no deletion was found, showed the deletion from at least exon 6 to the 5' end containing both muscle and brain promoters. In this case, a genomic deletion of the DMD gene contributed to the formation of tissues derived from both ectoderm and endoderm, and cells of mesodermal origin showed genotypic and phenotypic heterogeneity. Our results indicate a mutation of the present case may have occurred just before the period of germ layer formation.
Brain Chemistry↗
Interleukin-1 alpha is released during transfection of keratinocytes.
Keratinocytes are known to produce, store, and release IL-1 alpha and therefore we suspected that the DNA-mediated cell transfection procedure may release the stored IL-1 alpha from keratinocytes into the medium. Using enzyme-linked immunosorbent assay, we determined the IL-1 alpha concentration in culture supernatants during keratinocyte transfection. The following transfection methods were compared: lipofection with lipofectACE and lipofectAMINE (GIBCO), Ca3(PO4)2 co-precipitation, and polybrene-dimethylsulfoxide (DMSO). The supernatants were collected immediately prior to transfection, after 5-h incubation with lipofectin or Ca3(PO4)2, and 24 and 48 h after transfection. In the polybrene-DMSO method, the supernatant was also collected immediately before and after DMSO shock. LipofectAMINE caused the highest release of IL-1 alpha, whereas the lipofectACE and polybrene-DMSO mediated transfection with confluent cells released the least. The other two methods released intermediate levels of IL-1 alpha. Our data indicate that a substantial amount of IL-1 alpha is released during the keratinocyte transfection procedure, which can affect the results of transfection in studies of gene expression.
Cation Exchange Resins↗
Systemic lupus erythematosus with hereditary deficiency of the fourth component of complement.
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Adolescent↗
[A case of adult T-cell leukemia with various bone lesions].
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Adult↗
[Plasma exchange in 2 cases of hemolytic anemia].
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Adult↗