SYNDROME OF THE SEA-BLUE HISTIOCYTE —The First Case Report in Japan and Review of the Literature—

A case of the syndrome of sea-blue histiocyte is presented in a 53-year-old Japanese woman, which is the first recorded case in Japan. The patient had hepatosplenomegaly, bleeding manifestations, mild thrombocytopenia, fatty metamorphosis and cirrhosis of the liver, as well as abnormal serum lipid profiles. Her parents were consanguineous and her maternal grandmother with hepatomegaly died of hepatic failure. Histologically, peculiar histiocytes containing numerous, intracytoplasmic sea-blue stained granules on May-Giemsa stain were demonstrated in biopsy materials of the bone marrow, lymph node and liver. The sea-blue granules in these histiocytes proved to have histochemical staining characteristics of lipogenic ceroid-like pigment. Ultrastructurally, these granules showed membrane-bound, pleomorphic inclusions of heterogeneous nature, including electron-dense amorphous or variegatedly osmiophilic, frequently laminated materials. Enzyme cyto-chemically, localization of acid phosphatase activity was demonstrated in and around the intracytoplasmic inclusions. With regard to the pathogenesis of the sea-blue histiocytes in this case, it may be suggested that the existence of the abnormality in lipid metabolism plays an imporant role in intralysosomal ceroidogenesis in these histiocytes.     

The cytokines NAP-1 (IL-8), MCP-1, IL-1 beta,and GRO in rabbit inflammatory skin lesions produced by the chemical irritant sulfur mustard

Developing and healing dermal inflammatory lesions were produced in rabbits by the topical application of dilute sulfur mustard (SM),⁹ the military vesicant. In tissue sections of such lesions, cells containing the mRNA of important cytokines were identified with in situ hydridization techniques. These cytokines were neutrophil attractant/activation protein-1 (NAP-1 (also called IL-8)), monocyte chemoattractant (activating) protein 1 (MCP-1), interleukin 1 (beta) (IL-1 (beta)), and GRO (a growth factor and chemokine). Mononuclear cells (mainly macrophages and activated fibroblasts) contained the mRNA of all four of these cytokines. A higher percentage of cytokine-producing mononuclear cells (macrophages and activated fibroblasts) was present in lesions at 2 days (their peak size) than at 6 days, when they were almost healed. Granulocytes emigrated from the bloodstream, passed through the lesions, and were the major constituent of the protective crust. This sequence correlated with the distribution of cells able to produce NAP-1: At 2 days and 6 days, the mononuclears that contained messenger RNA for this granulocyte chemoattractant were found mainly in the upper part of the dermis. At 2 days and 6 days, cells containing the mRNA of IL-1, a primary cytokine, were also found predominantly in the upper dermis, i.e., nearest the site of injury. In contrast, mononuclears containing the mRNA of MCP-1 (a monocyte chemoattractant), and the mRNA of GRO (a granulocyte chemoattractant) were more equally distributed throughout the dermis. SM stimulated hair follicle epithelial cells to up-regulate GRO mRNA and, to a lesser degree, NAP-1 mRNA. Apparently, the irritation produced by SM directly or indirectly induces such epithelial cells to manufacture these growth factors. In the rabbit, hair follicles are known to be the main source of new epithelial cells after the covering epithelium has been destroyed. Therefore, GRO is probably a major autocrine-paracrine stimulus for such repair. A brief review of the role of cytokines in dermal inflammation is presented.Abbreviations SM Sulfur mustard: bis(2-chloroethyl)sulfide - GM-CSF Granulocyte-Macrophage Colony Stimulating Factor - GRO A member of the CXC subfamily of chemokines that promotes the multiplication of cells, formerly called melanoma growth stimulating activity (MGSA) - IFN (gamma)-Interferon-gamma - IL-1 Interleukin 1 - IL-8 Interleukin 8 (same as NAP-1)-a CXC chemokine - MCP-1 Monocy te Chemoattractant (Activating) Protein-1-a C-C chemokine - NAP-1 Neutrophil Attractant/Activating Protein-1 (same as IL-8)-a C-X-C chemokine - TGF (beta) Transforming Growth Factor (beta) - TNF (alpha) Tumor Necrosis Factor (alpha) - EDTA Ethylenediamine tetraacetate - DEPC Diethylpyrocarbonate - PBS Phosphate-buffered saline solution - PGE₂ Prostaglandin E₂ - PGI₂ Prostaglandin I₂ (prostacyclin) - SSC Sodium chloride-sodium citrate solution On leave of absence from the Institute for Medical Immunology, Kumamoto University School of Medicine, Kumamoto, Japan.On leave of absence from the Department of Internal Medicine, Oita Medical University, Oita, Japan.     

Overexpression of human thioredoxin in transgenic mice controls oxidative stress and life span

Transgenic (Tg) mice overexpressing human thioredoxin (TRX), a small redox-active protein, were produced to investigate the role of the protein in a variety of stresses. Bone marrow cells from TRX-Tg mice were more resistant to ultraviolet C-induced cytocide compared with those from wild type (WT) C57BL/6 mice. TRX-Tg mice exhibited extended median and maximum life spans compared with WT mice. Telomerase activity in spleen tissues in TRX-Tg mice was higher than that in WT mice. These results suggest that overexpression of TRX results in resistance against oxidative stress and a possible extension of life span without apparent abnormality in mammals.     

Cloning of a human immunoglobulin gene fragment containing both VH-D and D-JH rearrangements: Implication for VH-D as an intermediate to VH-D-JH formation

In an Epstein-Barr virus-transformed human B cell line we found an unusual immunoglobulin heavy chain gene rearrangement. Restriction mapping and sequencing analysis led us to conclude that V_H-D and D-J_H recombination took place in a single allele. Both V_H-D and D-J_H complexes still had their recombination signal sequences adjacent and the DNA sandwiched by these two complexes retained a germ line configuration, suggesting the potential for a secondary rearrangement resulting in a V_H-D(-D)-J_H formation. With this finding, we propose a novel pathway, in which the V_H-D complex is an intermediate in the formation of a functional V_H exon.     

Thioredoxin levels in the sera of untreated viral hepatitis patients and those treated with glycyrrhizin or ursodeoxycholic acid

Thioredoxin (TRX), a thiol-containing protein, is induced by various oxidative stresses. Serum TRX levels were measured with a sandwich enzyme-linked immunosorbent assay kit in 210 hepatitis C virus (HCV)-infected patients, 39 hepatitis B virus (HBV)-infected patients, and 17 healthy volunteers. The effects of hepatoprotective drugs on TRX levels were also examined. The median TRX levels were significantly higher in HCV-infected patients than in controls (34.2 vs. 23.5 ng/ml, respectively; p < 0.005), but were not elevated in HBV-infected patients (26.7 ng/ml). The TRX levels were significantly correlated with serum lipid peroxide levels and indocyanine green exclusion test values, and were markedly decreased following treatment with Stronger Neo-Minophagen C or ursodeoxycholic acid. In conclusion serum TRX levels, a marker of oxidative stress, were higher in patients with HCV infection than those with HBV infection and healthy controls. The therapeutic efficacy of hepatoprotective drugs may be connected with the decrease in oxidative stress in hepatitis patients.     

The gene encoding CD23 leukocyte antigen (FCE2) is located on human chromosome 19

Using Southern blot analysis of DNAs from human×rodent cell hybrids, we have mapped the CD23 leukocyte antigen gene (FCE2) to human chromosome 19.     

Dimerization and polymerization of butadiene with zero-valent nickel and protonic acids

The behavior of hydridonickel coordination compounds as catalysts for the oligomerization and polymerization of butadiene in various solvents was studied. In the presence of alcohol bis(tricyclohexylphosphine)chlorohydridonickel ( 4 , X = Cl) (HNiCl[P(C₆H₁₁)₃]₂) catalyzes the linear dimerization. With hydridotetrakis(phosphite)nickel(1+) ( 2 ) ([HNi{P(OR)₃}₄]⁺), which is prepared from tetrakis(phosphite)nickel ( 1 ) (Ni[P(OR)₃]₄) and trifluoroacetic acid, dimerization occurs in sec-alcohol but there is no reaction in tert-alcohol. The main product is 2-methylenevinylcyclopentane ( 8 ). The other products are 4-vinylcyclohexene ( 10 ), 1,5-cyclooctadiene ( 5 ), 1,3,7-octatriene ( 7 ) and 1,3,6-octatriene ( 9 ). The hydridonickel coordination compound, prepared with inorganic acids, does not afford the dimers but the 1,4-trans polymer.