Takao Nakamura

Dermatopathological studies on skin lesions of MRL mice

SummaryThe MRL-lpr/lpr(MRL/l) mouse is a new animal model for human systemic lupus erythematosus (SLE) and skin lesions with hair loss and scab formation are one of the characteristic manifestations in this mouse. We investigated the histopathology of the skin lesions in MRL/l mice and studied the related autoimmune phenomenon. Light microscopical observations revealed hyperkeratosis, acanthosis, hypergranulosis, liquefaction, vasodilation in the dermis and T-cell infiltration into the dermis at the age of 5 months (mo). Immunohistological studies showed the presence of immunoglobulins and/or complement depositions at the dermal-epidermal junction (DEJ). In some mice there was deposition of immunoglobulin at the DEJ at 2 mo and in 90%–100% of MRL/l mice at over 5 mo. Temporal relationship was present among cutaneous immunoglobulin depositions, the occurrence of anti-DNA antibodies and proteinuria. These findings suggest that MRL/l mice might provide a new aid for studying the biological mechanisms of the development of skin lesions in human SLE.

An AP-FIM study on metastable phases in AlAg binary alloy

Abstract The morphology and chemical composition of metastable phases in an Al-5.72at.% Ag alloy have been investigated by means of atom-probe field ion microscopy. It was found that the η G.P. zones formed by aging at 413 K have an average solute concentration of 45.8 ± 0.7 at.% Ag. the present data on zone size and interparticle distance were found to be consistent with data determined by small-angle X-ray scattering. When the specimen was aged at 436 K for 60 ks, both ϵ G.P. zones and γ′ metastable phase were observed simultaneously. The solute concentration of ϵ zones was determined to be 35.7 ± 0.2 at.% Ag. The γ′ phase was a plate-like precipitate lying on the {111} matrix plane, and its solute concentration was 33.3 ± 1.5 at.% Ag and its thickness was in the range of 2.3–7.0 nm. By combining the present data with other results certain pending questions on the structures of metastable phases in this alloy have been successfully solved.

Allogeneic bone marrow-plus-liver transplantation in the C57BL/KsJ spm/spm mouse, an animal model of Niemann-Pick disease.

The C57BL/KsJ spm/spm mouse, an animal model of Niemann-Pick disease, shows defective sphingomyelinase activity resulting in accumulation of sphingomyelin in various organs. To replace the defective enzyme, allogeneic bone marrow-plus-liver transplantation was performed. Bone marrow transplantation with or without concomitant liver grafting in C57BL/KsJ spm/spm mice at the age of 2–9 weeks led to an amelioration of the hepatosplenomegaly. The treatment, however, neither prevented the development of neurological signs nor increased the life-span. The sphingomyelin and cholesterol contents of the liver decreased, while sphingomyelinase activity in the liver increased after bone marrow transplantation. Foam cells disappeared from the bone marrow, liver, spleen, thymus, and lymph nodes, but depletion of Purkinje cells was not prevented. These results suggest that bone marrow transplantation either alone or with liver transplantation may become a useful strategy for the treatment of Niemann-Pick disease provided the central nervous system is not involved.

Two natural killer-cell subpopulations distinguished by heat sensitivity

We examined the effect of heat on natural killer-cell activity and found that two different natural killer-cell subpopulations can be distinguished by their heat sensitivity; one subpopulation loses natural killer-cell activity at 41°C, and the other is not affected. In a single-cell assay, the ability of natural killer cells to conjugate to K 562 cells was not affected by incubation at 41°C, but the killer activity of natural killer cells after conjugating to K 562 cells was reduced at 41°C. Therefore it is likely that the difference in heat sensitivity between the two subpopulations is due to postbinding cytolytic events. Tetracaine, which influences cytolytic events, was used to examine whether or not the two natural killer-cell subpopulations can be distinguished by tetracaine sensitivity. However, it was found that tetracaine inhibits natural killer-cell activity equally for both of these natural killer-cell subpopulations.

Fate of Engrafted Skin in Thymic Chimeras

There have been some investigations concerning the mechanisms of self-toler anceusing thymic chimeras with organ transplantation. In heart transplantation to nude mice bearing allogeneic thymus, Seger et al (15) found that neonatal heart grafts of thymus donor origin were rejected, but another group (17) showed that they were accepted. There are also conflicting reports regarding the fate of engrafted skin on thymus chimeras. Kindred and Loor (12) studied the mode of skin grafts in BALB/c nu/nu mice engrafted with C57BL/6 thymus and found that some mice accepted but some mice rejected the skin of the thymus donor. However, Pritchard and Micklem (14) observed that thymic chimeras accepted the skin of the thymus donor and rejected the skin of a third party. Recently, some groups (3, 6, 8) demonstrated that thymic chimeras accepted the skin of both thymus-type and host-type. In spite of this accumulated evidence, the effects of donor and host conditions on the fate of en graftedskins described below have not been considered precisely. The final goal of these studies is to establish an immunological requirement for treatment of pa tientswith immunodeficiency by thymus grafting. Therefore, it is very important to elucidate whether the conditions in host and donor, even if they are not major problems, affect the fate of engrafted skin. In this study our attention was focused on the following factors: 1) the presence of postthymic T cells in nude mice and the possibility of these T cells expanding under the influence of the engrafted thymus (7), 2) the effect of immunocompetent T cells in the engrafted thymus, 3) the size of engrafted skin (16), and 4) the duration of engrafted skin survival because skin antigen presenting cells take 65-80 days to be replaced by bone marrow precursors