Quantitative genetic variation in CD19 expression correlates with autoimmunity

Signaling thresholds influence the balance between humoral immunity and autoimmunity. Cell surface CD19 regulates intrinsic and Ag receptor-induced B lymphocyte signaling thresholds, and transgenic mice that overexpress CD19 by 3-fold generate spontaneous autoantibodies in a genetic background not associated with autoimmunity. To quantify the extent that genetically determined differences in expression of a single cell surface molecule can influence autoantibody production, we have assessed autoimmunity in a C57BL/6-transgenic mouse line with subtle 15-29% increases in CD19 cell surface expression (CD19 transgenic). Antinuclear Abs, especially anti-spindle pole Abs, rheumatoid factor, and autoantibodies for ssDNA, dsDNA, and histone were produced in these transgenic mice, but not littermate controls. This demonstrates that small changes in CD19 expression can induce autoantibody production. Remarkably, similar changes in CD19 expression were found on B cells from patients with systemic sclerosis, a multisystem disorder of connective tissue with autoantibody production. CD19 density on blood B cells from systemic sclerosis patients was significantly ( approximately 20%) higher compared with normal individuals, whereas CD20, CD22, and CD40 expression were normal. These results suggest that modest changes in the expression or function of regulatory molecules such as CD19 may shift the balance between tolerance and immunity to autoimmunity. Thereby autoimmune disease may result from a collection of subtle multigenic alterations that could include incremental density changes in cell surface signaling molecules.     

HMB-45 staining for cytology of primary melanoma of the vagina. A case report

BACKGROUND: Malignant melanoma in the vagina is very rare, but its diagnosis is usually easy if a melanin pigment is present. With cytodiagnosis, however, it is difficult to differentiate amelanotic melanoma or scantily pigmented melanoma from other conditions. In the present case, monoclonal antibody HMB-45, the efficacy of which has been established in histologic studies, was used in the cytodiagnosis of amelanotic melanoma in the vagina. CASE: A woman, aged 78 years, presented with a brownish, nodular tumor, diameter 3 cm, in the vagina. Scraping smears with Papanicolaou staining showed nonepithelial malignant cells without granules suggesting melanin. Smears stained with HMB-45 showed positive immunoreactivity. The diagnosis underwent histologic confirmation of amelanotic melanoma on the initial biopsy. CONCLUSION: Cytodiagnosis was made with HMB-45, which proved very effective in the differential cytodiagnosis of amelanotic melanoma and scantily pigmented melanoma, particularly because it obviated the need for tissue invasion.     

The inhibitory effects of mushroom extracts on sucrose-dependent oral biofilm formation

Mushrooms contain large quantities of α-glucans. Shiitake (Lentinula edodes), Japan’s most popular edible mushroom, has been reported to contain about 6% (weight/dried weight) of α-(1,3)-glucan. This glucan is one of the major components of oral biofilm formed by the cariogenic bacteria Streptococcus mutans and Streptococcus sobrinus. We found that extracts from shiitake and other edible mushrooms could reduce preformed biofilms of S. mutans and S. sobrinus in the presence of dextranase. We also investigated the α-glucanase activities of shiitake mushroom extracts and their effects on biofilm formation. The extracts possessed α-glucanase activity and degraded water-insoluble glucans from mutans streptococci. The extracts strongly inhibited the sucrose-dependent formation of biofilms by S. mutans and S. sobrinus in the presence of dextranase. Our results suggest that some components of mushrooms, including α-glucanases, might inhibit the sucrose-induced formation of oral biofilms.     

Synthesis,in vitro and in vivo studies of Gd-DTPA-XDA-D1-Glc(OH) complex as a new potential MRI contrast agent

A new type of dendritic molecules Gd-DTPA-XDA-D1-Glc(OH), which work as a functionalized ligand coordinating gadolinium(III) ion at the center of their frameworks with two glucose moieties on the molecular surfaces, were readily synthesized with high yield. The structures were established by IR, ¹H, ¹³C NMR, and mass spectral studies. Its bio-distribution patterns were evaluated on rats.     

High-yield production of short chain length poly(ε-<Emphasis Type="SmallCaps">l</Emphasis>-lysine) consisting of 5–20 residues by <Emphasis Type="Italic">Streptomyces</Emphasis><Emphasis Type="Italic">aureofaciens</Emphasis>, and its antimicrobial activity

Poly(ε-l-lysine) (ε-PL) is a naturally-occurring l-lysine homopolymer having antimicrobial activity. A newly-isolated strain of Streptomyces aureofaciens produced a short chain length ε-PL consisting of 5–20 residues at the highest production level of 4.5 g l^–1. This ε-PL had different spectra in terms of antimicrobial activity from the ε-PL that is now used as a food preservative. The high productivity was based on multiple metabolic pathways for l-lysine synthesis, and a great flux from l-lysine to ε-PL. The usefulness of this new ε-PL and its producing strain was discussed.     

Alterations in hepatitis B virus nucleotide sequences in a chronic virus carrier from immunotolerant to immunoactive phase

Factors involved in transition from the immunotolerant to immunoactive phase in chronic hepatitis B virus (HBV) infection remain unclear. We investigated viral mutations occurring during transition and elucidated their virological and immunological significance. Full-length HBV DNA sequences were serially determined in a chronic HBV carrier from the immunotolerant to immunoactive phase. Viral replicative competence was examined by transfection analysis. HBV-specific CD8⁺ T cell response was evaluated by coculture of CD8⁺ T cells with autologous dendritic cells followed by interferon-γ Elispot assay. Eleven point mutations and two deletions appeared around the onset of the immunoactive phase. Viral replicative competence declined significantly after the onset of active hepatitis. Examination of the CD8⁺ T cell response against two putative T-cell epitopes, which contained substituted amino acids from the immunotolerant to immunoactive phase, showed that mutant HBV epitopes gave a lesser T cell response than wild-type HBV ones. In summary, point mutations and deletions may occur prior to or concurrent with the onset of the immunoactive phase during chronic HBV infection. These mutations may result in a significant decrease in both viral replicative competence and HBV-specific CD8⁺ T cell response, suggesting a possible adaptation for the maintenance of viral persistence.     

Lignans of Larix leptolepis

Five lignans have been isolated from wood of Larix leptolepis. They are identified as 1-(4-hydroxy-3-methoxyphenyl)-2-4-[2-formyl-(E)-vinyl]-2-methoxyphenoxy-propane- 1,3-diol, 1-(4-hydroxy-3-methoxyphenyl)-2-2-methoxy-4-[1-(E)-propen-3-ol]-phenoxy- propane-1,3-diol, 1-(4-hydroxy-3-methoxyphenyl)-2-(4-formyl-2-methoxyphenoxy)-propane-1,3-diol, 1,2-bis-(4-hydroxy-3-methoxyphenyl)-propane-1,3-diol and a trilignol, leptolepisol C.     

Substantially monodispersed poly(ɛ-<Emphasis Type="SmallCaps">l</Emphasis>-lysine)s frequently occurred in newly isolated strains of <Emphasis Type="Italic">Streptomyces</Emphasis> sp.

The presence of poly(epsilon-L-lysine) (epsilon-PL) was found quite frequently by screening various strains of Streptomyces sp. Most of the ten newly obtained epsilon-PLs, when they were produced from glucose, showed a polydispersity index of Mw/Mn = 1.01 using ion-pair chromatography analysis. The polymers were classified into five groups according to their chain lengths. The average numbers of residues in the five groups were 32, 28, 25, 19, and 16, respectively. The use of glycerol instead of glucose resulted in decreases of 10 to 20% in the Mn and slight increases in the Mw/Mn. These observations indicated the chain length and polydispersity of epsilon-PL were primarily determined by each producer strain. Proton and 13C NMR analysis revealed the signals of glycerol-derived ester at the C terminus of the polymer from several producers including the first discovered S. albulus strain, although the percentages of the ester were low under our culture conditions. These results, coupled with the previous observation that SO4(2-) was essential for the polymer production, led to discussion on the mechanistic aspects of monomer activation, elongation, and termination in the biosynthesis of epsilon-PL.