The mouse homolog of Drosophila Vasa is required for the development of male germ cells.

Restricted expression of a mouse Vasa homolog gene (Mvh) expression is first detected in primordial germ cells (PGCs) after colonization of the genital ridges. Subsequently, Mvh is maintained until postmeiotic germ cells are formed. Here, we demonstrate that male mice homozygous for a targeted mutation of Mvh exhibit a reproductive deficiency. Male homozygotes produce no sperm in the testes, where premeiotic germ cells cease differentiation by the zygotene stage and undergo apoptotic death. In addition, the proliferation of PGCs that colonize homozygous male gonads is significantly hampered, and OCT-3/4 expression appears to be reduced. These results indicate that the loss of Mvh function causes a deficiency in the proliferation and differentiation of mouse male germ cells.

Generalized melanosis in metastatic malignant melanoma: the possible role of DOPAquinone metabolites.

Generalized melanosis occurs very rarely as a complication of malignant melanoma, and the pathogenesis of this condition is still unclear. Histological examination of pigmented skin and measurements of the DOPAquinone metabolites 5-S-cysteinyldopa (5-S-CD) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) in the patient's serum and urine were carried out. Histological examination revealed basal hyperpigmentation, discrete melanoma cells and melanophages around the blood vessels and an unusual melanin deposition within collagen bundles in the dermis. The levels of 5-S-CD and 6H5MI2C were dramatically increased both in the patient's serum and urine. The deposition of DOPAquinone metabolites secreted by the melanoma cells may contribute to the unusual melanin deposition within collagen bundles in the affected dermis.

Dermatoscopic and videomicroscopic features of melanocytic plantar nevi.

Nearly 10% of Japanese people have pigmented nevi on the soles. Since malignant melanoma also occurs on the plantar area in the Japanese, it would be very valuable to be able to differentiate benign and malignant lesions in the early clinical state. We have investigated the epiluminescence microscopic features of 500 melanocytic nevi on the soles of Japanese people using a dermatoscope and a videomicroscope that can magnify lesions from x 10 to x 200. The results showed that the surface profile of benign melanocytic nevi is mainly classified into five types; that 9% of plantar nevi, however, do not fit into this classification and are categorized as a miscellaneous type; and that the other nonmelanocytic disorders, such as verruca vulgaris and black heel, are easily differentiated by their surface profile. More important, the histological examination showed that atypical nevi, malignant melanoma in situ, and acral lentiginous melanoma are exclusively compartmentalized in the miscellaneous type of surface profile. Our data suggested that epiluminescence microscopy may be a useful method for discrimination of plantar benign and malignant melanocytic lesions.

Characterization of the mononuclear infiltrate involved in regression of halo nevi.

Halo nevi are characterized by progressive degeneration of nevus cells surrounded by a mononuclear cell infiltrate. We studied the morphological features of the nevus cells and the composition of the mononuclear cell infiltrate in 15 cases of halo nevi using immunohistochemical techniques and a battery of antibodies to different subsets of lymphocytes and histiocytes. Regression could be divided into four more or less identifiable stages, associated with different subsets of lymphocytes and monocyte-macrophage lineage cells. Stage I (preregression): nests of unremarkable nevus cells were surrounded by a moderate number of T lymphocytes (relatively small percentage of helper inducer T cells), occasional B cells and macrophages. Stage II (early regression): large number of T lymphocytes and FXIIIa-positive cells were in close contact with nevus cell clusters which showed ragged edges. Lysozyme-positive cells and epidermal Langerhans cells were mildly increased. Stage III (late regression): single nevomelanocytes showing mild atypia were present. Numerous T lymphocytes and macrophages positive for lysozyme, KP1 and/or FXIIIa were interspersed between the nevus cells. Increased numbers of epidermal Langerhans cells were present. Stage IV (complete regression): no nevus cells were observed and moderate numbers of T lymphocytes only remained. These results suggest that T cells, especially T-suppressor cells, and different subsets of macrophages participate in the regression of the nevi.

Lymphocyte and macrophage subsets in active and inactive lesions of lichen planus.

Lichen planus (LP) is a mucocutaneous disease for which the etiology and pathogenesis are poorly understood. We performed an immunohistochemical study on formalin-fixed tissue sections of 10 cases of LP using subsets of antibodies to lymphocytes (LCA, CD3, OPD4-CD4, L26, LN1 and Leu-7), and monocyte-macrophages [lysozyme, KP1-Mac, Factor XIIIa (FXIIIa) and S-100 protein]. Six cases showed typical histological features of active LP, two cases showed features of active and inactive LP, and two cases showed only inactive LP. In active LP, scattered T cells (CD3+ and pan T cells) were present in the epidermis, whereas large numbers of CD3+ T cells were present at the dermoepidermal junction and in the dermis. Approximately 40% of the T cells at the dermoepidermal junction were of the helper/inducer subset, whereas approximately 80% of those in the dermis were CD4 positive (helper/inducer T cells). Occasional B cells were present in the dermis only. Increased numbers of S-100-positive Langerhans cells, macrophages expressing lysozyme, and FXIIIa dendritic cells were present in the epidermis and dermis. The inactive lesions showed the presence of a few epidermal Langerhans cells and a mild infiltrate of T cells (helper/inducer subset). These results suggest that in addition to different subsets of T cells and macrophages, including Langerhans cells, dermal dendritic cells expressing Factor XIIIa and lysozyme-positive histiocytes play an important role in lichen planus. They may participate in the destruction and subsequent regeneration of the basal layer of the epidermis, or alternatively may be activated as a result of destruction of the basement membrane in LP.

Reconstitution of severe combined immunodeficient mice with intrathyroidal lymphocytes of thyroid xenografts from patients with Hashimoto's thyroiditis.

Thyroid tissues from patients with Hashimoto's thyroiditis (HT) have been xenografted to both severe combined immunodeficiency (SCID) mice and nude mice to study the intrathyroidal lymphocytes which were expected to migrate from the xenografts in the SCID mice. Peripheral blood mononuclear cells from HT, Graves' disease, and normal donors have also been separately engrafted. SCID mice, but not nude mice with HT thyroid grafts produce human immunoglobulins. More immunoglobulin G (IgG), but less IgM and IgA is produced in SCID mice with HT thyroid grafts (SCID-TH), compared to SCID mice injected with peripheral blood mononuclear cells from patients with HT or normal donors (SCID-PB), suggesting that different B cell subpopulations were active in the SCID-PB vs. SCID-TH. Production of IgG by SCID-PB and SCID-TH was maintained 6 weeks after engraftment, and decreased thereafter. SCID mice but not nude mice grafted with HT thyroid tissue produce antibodies to thyroglobulin and thyroperoxidase. Lymphocytes within intact HT thyroid grafts persist in SCID mice, and migrate to the spleen, whereas human lymphocytes do not survive in the thyroid grafts or other tissues of the nude mouse. In 6 weeks, the xenografts in nude mice became histologically normal. In contrast, xenografts from SCID mice showed more marked inflammatory changes than in the original human lesion, although the ratio of T/B cells is unchanged. This worsening of the lesion may relate to the increase in activation of the T-lymphocytes.

Lymphocyte markers on formalin-fixed tissue in Jessner's lymphocytic infiltrate and lupus erythematosus.

Clinical and histological differentiation between Jessner's lymphocytic infiltration of the skin (JLI) and lupus erythematosus (LE) may be difficult. Previous immunohistochemical studies using monoclonal antibodies on frozen sections have shown that the majority of inflammatory cells in JLI and LE are T lymphocytes, whereas B lymphocytes are few or absent. We have performed an immunohistochemical study on formalin-fixed, paraffin-embedded tissue sections from seven patients with JLI and five with LE using monoclonal antibodies MT1 (pan T-cells), OPD4 (helper/inducer T-cells CD4), MT2 (mantle zone B and some T-cells), MB2 (pan B-cells), L26 (pan B-cells), and LN1 (germinal centre B-cells). In both diseases, the-majority of the inflammatory cells were T lymphocytes (MT1 positive), confirming the results others have obtained on frozen material. OPD4 positive cells were detected in varying numbers in all cases. However, the percentage of B lymphocytes tended to be higher in JLI than LE. LN1 was the most useful B-cell marker in distinguishing JLI from LE. However, a combination of MT2 and LN1 gave the most significant difference. We conclude that immunohistochemical analysis using a panel of monoclonal antibodies to T and B lymphocytes may be useful in differentiating JLI from LE, although there is still considerable overlap.

Localized myxedema on the nasal dorsum in a patient with Graves' disease: report of a case.

We report the case of a 56-year-old Japanese female with Graves' disease associated with localized myxedema on the nasal dorsum. The patient developed localized myxedema concomitantly with hyperthyroidism before antithyroid therapy was given. The lesion was totally removed surgically, as it was small and well circumscribed. Although unusual locations of localized myxedema have been reported elsewhere, there is to date no case of localized myxedema on the nasal dorsum without involvement of the pretibial area reported in the literature. We discuss this unique feature of our patient.