Heihachiro Kashiwagi

Diversities in animal vitronectins differences in molecular weight immunoreactivity and carbohydrate chains

Six animal plasma vitronectins, human, horse, porcine, bovine, rabbit and chicken vitronectins purified by a novel method using two successive heparin affinity columns, showed marked diversity in molecular weight, immunoreactivity and carbohydrate composition. Chicken vitronectin had a distinctly different amino acid composition from the mammalian vitronectins; and bovine vitronectin was the only one to contain N-glycolylneuraminic acid as well as N-acetylneuraminic acid. Binding studies with horseradish peroxidase-labelled lectins indicated that all the vitronectins contained complex-type, sialylated N-linked sugar chains and that only porcine vitronectin had a fucosylated sugar chain. D-Galactosamine determinations and binding studies with horseradish peroxidase-peanut lectin on native and asialovitronectins revealed that the mammalian vitronectins other than human vitronectin contained O-linked sugar chains with sialic acid, chicken vitronectin contained unsialylated chains, and human vitronectin contained neither. The results indicate that diversities in vitronectins are apparent in their molecular weights and glycosylations, especially in the number and structure of O-linked sugar chains.

Weight Reduction in Athletes May Adversely Affect the Phagocytic Function of Monocytes

In brief: Monocyte phagocytic function was studied in nine competitive athletes before and after a two-week weight-reduction program of calorie restriction. The phagocytic activity of monocytes before the program was higher in the athletes than in the sedentary controls, but decreased significantly after the weight-reduction program. Furthermore, plasma fibronectin concentrations and the response of lymphocytes to phytohemagglutinin decreased after the calorie restriction. These findings suggest that weight reduction by calorie restriction may adversely affect the integrity of defense mechanisms, even in healthy athletes. Thus, calorie restriction in athletes must be conducted with caution to protect them from adverse effects on their physiologic defense mechanisms.

Molecular biology of cytokine effects on vascular endothelial cells.

Publisher Summary This chapter discusses molecular biology of cytokine effects on vascular endothelial cells. Vascular endothelial cells constitute the luminal surface of the vascular system and play an active role in normal hemostasis and in various pathophysiological responses, such as inflammation, wound healing, selective transfer of substances to and from the circulation, and regulation of vascular tonus. Positioned at the interface between circulating blood and the subendothelial vascular structures, endothelial cells (ECs) mediate the effects of products and signals released from ECs to the vascular wall. For these reasons, functional and structural abnormalities of ECs might contribute significantly to vascular pathology such as thrombosis, atherosclerosis, and vasculitis. The demonstration that hemostasis, inflammation, and immunity involve close interactions between immunocompetent cells and vascular ECs has marked an important advance in understanding the role of ECs. Cytokines, produced by and acting on ECs, are mediators of the complex bidirectional interactions between immunocompetent cells and ECs. Cytokines affect EC function in inflammation, thrombosis, angiogenesis, and immune responses.

A novel antibody wich precipitates 7.5S RNA is isolated from a patient with autoimmune disease

Abstract We have isolated a nobel antibody from a patient with autoimmune disease which reacts with the ribonucleoprotein complex containing 7.5S RNA. The 7.5S RNA consists of two species having slightly different electrophoretic mobilities. Fingerprinting analysis of these two species demonstrates that nucleotide sequences of the RNAs are very similar to each other. Nucleotide composition of the 7.5S RNA is found to be; A/U/G/C=20/18/32/30, indicating that the ratio of GC content of the RNA(62%) is relatively high. The RNA contains a pseudouridylic acid residue as a modified nucleotide. Immunofluorescence pattern stained with the antibody suggests that the ribonucleoprotein complex containing 7.5S RNA is located both in the nucleolus and the cytoplasm.

Clinical Features of Patients with Mild Systemic Lupus Erythematosus

Clinical features of 16 patients with mild systemic lupus erythematosus (SLE) were compared with those of 21 control patients with moderate or severe disease. Age at the time of diagnosis of SLE was higher in mild disease group. The incidence of the coexistence of Sjögrens syndrome (SS) at the time of diagnosis of SLE was higher in patients who later developed mild disease. Anti-Sm antibody and decreased levels of C3, C4, and CH50 occurred less frequently in patients with mild disease. SLE patients with the coexistence of SS at the time of diagnosis of SLE may represent a subset with a benign prognosis.

Characterization of genomic polymorphism of an activation-associated antigen, Blast-1.

Blast-1 is a human activation-associated glycoprotein expressed on the surface of monocuclear cells, and a possible genetic marker for the manifestation of rheumatoid arthritis. In the present study, genomic polymorphism of the Blast-1 gene was analyzed using 100 healthy subjects. Restriction fragment length polymorphism (RFLP) of the Blast-1 gene was recognized only by Bam HI digestion among 46 restriction enzymes tested. The sizes of polymorphic fragments were 2.4 kilobase (kb) on the L band, and 1.9 kb on the S band. A family study demonstrated that the two alleles of the Blast-1 gene were inherited in a co-dominant Mendelian fashion. The genotype frequencies of homozygosity for the L and S bands were 47% and 42%, respectively, while the frequency of heterozygosity was 11%. The allele frequencies of the L and S bands were 0.68 and 0.32, respectively. The distribution of the Blast-1 genotypes in the present study was concordant with Hardy-Weinberg equilibrium (p>0.7), which indicates that the frequency of the Blast-1 gene in the population is derived from random mating in preceding generations. The results of the present study may provide useful information in disease associations with the Blast-1 gene.

Recombinant Interleukin-1 Triggers the Increase of Circulating Fibronectin Level in Rats

Interleukin-1 (IL-1) is one of the mediators responsible for the acute phase protein response during inflammation. We evaluated the effect of recombinant IL-1 alpha given intra-abdominally on rat circulating fibronectin (Fn) levels. Circulating Fn level, sampled between 3 h and 7 days after injection, was maximum at 24-48 h in Wistar rats treated with IL-1 at doses of 10 U and 100 U/100 g body weight (BW), respectively. Circulating Fn level in rats injected with 100 U/100 g BW IL-1 was higher than that of rats given 10 U/100 g BW IL-1. Circulating Fn level peaked at 24 h, whereas albumin levels decreased by 10% at this time. When frozen tissue sections of rat liver were examined using anti-Fn antibodies, the immuno stainings were denser in IL-1-treated animals than in controls. These findings suggest that IL-1 triggers plasma Fn production by the liver.

Classification tree criteria of pulmonary hypertension in mixed connective tissue disease

Tree criteria for the classification of pulmonary hypertension (PH) in mixed connective tissue disease (MCTD) were developed by stratifying patients into groups according to the physician’s diagnosis, mean pulmonary artery pressure (mPA) and prognosis, respectively. A classification tree for PH diagnosed by the physician was constructed with two criteria: dilatation of the pulmonary artery segment evident on chest roentgenography (or an accentuated pulmonic sound as a surrogate) and shortness of breath on exertion, which demonstrated a sensitivity of 96% and a specificity of 99%. A classification tree for PH diagnosed by mPA was also constructed with almost similar criteria: an accentuated pulmonic sound (or dilatation of the pulmonary artery segment evident on chest roentgenography as a surrogate) and shortness of breath on exertion, which demonstrated a sensitivity of 100% and a specificity of 100%. The prognostic classification tree was constructed with four criteria: an accentuated pulmonic sound, systolic pulsation at the left sternal border, shortness of breath on exertion and retro-sternal pain on exertion, which demonstrated a sensitivity of 62% and a specificity of 98%. The classification tree criteria for the diagnosis and prognosis of PH in MCTD were found to be accurate and useful for the screening of PH.

Monocyte-mediated suppression of T lymphocyte blastogenesis and its reversal by deoxyguanosine. Defects in patients with systemic lupus erythematosus

We investigated monocyte-mediated suppression of T lymphocyte blastogenesis in normals and patients with systemic lupus erythematosus (SLE). When monocytes from normals were cocultured with autologous T lymphocytes with a ratio of 1:1 and stimulated with phytohemagglutinin (PHA), 3H-thymidine incorporation by T lymphocytes was suppressed. This monocyte-mediated suppression was reversed by purine nucleoside phosphorylase substrate, deoxyguanosine. In SLE patients, both monocyte-mediated suppression and its reversal by deoxyguanosine were defective. The defective function was observed both in patients with active and inactive diseases. The defective function was studied sequentially before and after change in the clinical status of patients. The defects remained unaffected regardless of the disease activity. The defects in monocyte-mediated suppression and its reversal by deoxyguanosine in SLE patients as demonstrated in our study suggest the presence of intrinsic monocyte dysfunction in SLE.

Gelatinous transformation of bone marrow with pancytopenia in an emaciated patient with systemic lupus erythematosus

We report on gelatinous transformation of the bone marrow in a 42-year-old male patient with systemic lupus erythematosus (SLE). Gelatinous transformation of the bone marrow in SLE is rare. This condition is composed of hypocellularity with deposition of hyaluronic acid in the bone marrow and is known to be associated with malnutrition due to cachexia and anorexia nervosa. In this patient we consider that malnutrition caused gelatinous transformation which worsened pancytopenia due to SLE. Pancytopenia improved after methylprednisolone pulse therapy and nutrition therapy.