Two distinct monoclonal natural thymocytotoxic autoantibodies from New Zealand black mouse

Autoimmune-prone NZB and NZB x NZW F1 mice have a large amount of autoantibodies cytotoxic for thymocytes (natural thymocytotoxic autoantibodies, NTA). We established two distinct monoclonal NTAs (NTA260 and NTA204) from a NZB mouse that react with the majority, but not all of these thymocytes. Flow cytometry analysis showed that NTA260 is positive on subpopulations of peripheral T cells from young mice, in which approximately 65% of CD4+ and 85% of CD8+ T cells were NTA260+. NTA260 also reacted with brain tissues of mice and rats, including Purkinje cells in the cerebellum. Western blot analysis showed that the molecular weight of NTA260 antigen was 55 kDa. In contrast to NTA260, NTA204 reacted with peripheral B cells but not with peripheral T cells in mice. NTA204 also reacted with peripheral blood granulocytes and bone marrow myeloid cells from both mice and rats. An immunofluorescence inhibition assay revealed the presence of autoantibodies with specificities of each NTA260 and NTA204 in the sera from NZB mice. As a selective decline in the subset of NTA260+ T cells but not NTA204+ B cells was observed with aging of NZB and NZB x NZW F1 hybrid mice, NTA260 is at least partly related to the observed immunological abnormalities of T cells in these autoimmune-prone New Zealand mice.     

ABC proteins: key molecules for lipid homeostasis

Forty-nine ABC protein genes exist on human chromosomes. Eukaryotic ABC proteins were originally recognized as drug efflux pumps involved in the multidrug resistance of cancer cells. However, it is now realized that one of their major physiological roles is cellular lipid transport and homeostasis, and their dysfunction is often associated with human diseases. ABCA1 and ABCA7 mediate the apolipoprotein-dependent formation of a high-density lipoprotein–cholesterol complex. ABCA3 is indispensable for pulmonary surfactant secretion. ABCG5 and ABCG8 are involved in the secretion of plant sterols and cholesterol into bile. However, the primary substrates and mechanism of action of these ABC proteins have not been precisely defined. In this review article, we first describe the general structure and functions of eukaryotic ABC proteins. The current model of ABCA1 functionality is then explained based on studies on a topological model, subcellular localization, apoA-I dependence of HDL formation, functional defects of Tangier disease mutants, and ATP hydrolysis of purified ABCA1. ABCA1 is supposed to function as a transporter of lipids as well as a receptor for apoA-I. ABCA3 is likely involved in accumulating phospholipids and cholesterol in lamellar bodies and in generating multivesicular structures.     

Presynaptic opioid kappa-receptor and regulation of the release of Met-enkephalin in the rat brainstem

Opioid kappa-agonists had much more potent inhibitory effects on the high K+-evoked Met-enkephalin release from rat brain slices than did the mu- or delta-agonists. The opioid kappa- antagonist, MR2266 enhanced the evoked release of Met-enkephalin to a greater extent than did mu- or delta-antagonists in vitro and had a potent analgesia in mice in vivo. These findings suggest that the release of Met-enkephalin may be regulated in vitro and in vivo, mainly by presynaptic kappa-receptor-mediated mechanisms.     

CD69-null mice protected from arthritis induced with anti-type II collagen antibodies

CD69, known as an early activation marker antigen on T and B cells, is also expressed on platelets and activated neutrophils, suggesting certain roles in inflammatory diseases. In order to address the role of CD69 in the pathogenesis of arthritis, we established CD69-null mice. CD69-null mice displayed a markedly attenuated arthritic inflammatory response when injected with anti-type II collagen antibodies. Cell transfer experiments with neutrophils, but not T cells or spleen cells, from wild-type mice into CD69-null mice restored the induction of arthritis. These results indicate a critical role for CD69 in neutrophil function in arthritis induction during the effector phase. Thus, CD69 would be a possible therapeutic target for arthritis in human patients.     

Slight difference in primary amino acid sequence of p17 matrix protein of HIV-1 exerts profound influence on its antigenicity

Summary.  HIV-1 p17 antigen has been studied for its biological significance in vitro as well as its immunological roles in vivo. By immunological approach of antibody-binding to HIV-1 p17 antigens of several subtypes in combination with computerized analysis of those tertial structures, it became evident that, irrelevant of similarity of linear amino acid sequence of different HIV-1 subtypes, a few amino acid substitutions close to or distant from specified epitope(s) affected their tertial structure resulting in change in ability of its binding to selected antibody. ELISA employing two monoclonal antibodies, A144 and C415, could detect p17 of subtypes A and B, but not of subtypes C, D, and E. Since the epitope site corresponding to A144 has been reported to be important for biological activity of p17 of HIV-1, change in tertial structure around this epitope may explain some difference in biology of HIV-1, such as infectivity of subtypes B and E. Accepted January 9, 1998 Received October 24, 1997     

Practical application of nutritional assessment protein and inflammatory marker in the nutrition support team (NST)

Recently nutrition support team (NST) has been established for the purpose of prevention of complications which are caused by nutrition disorders and reduction of the medical expenses. Although physical examinations and blood biochemical data had been used as the indexes evaluating nutritional of patients, they were not suitable for the evaluation for the short-term in-patient. On the contrary, serum albumin (ALB) has been wildly used as a nutritional marker. However, it is impossible to evaluate nutrition state for the short-term in-patient and acute phase disease patient accurately, because the plasma half-life is 21 days and it takes long time to detect the change in nutritional state by its value. Rapid turnover proteins (RTP), whose plasma half-life is shorter, has paid attention to evaluate nutritional state for the short-term in-patients and acute phase disease patients. Although, prognostic inflammatory and nutritional index (PINI) was considered as a useful maker for evaluating inflammatory and nutritional states using the concentrations of transthyretin (TTR), a RTP, alpha1-acid glycoprotein (alpha1-AG), a chronic inflammation marker, C reactive protein (CRP), a acute inflammation marker, and ALB, However, it has several pitfalls. We newly made serum amyloid A (SAA) index using SAA instead of CRP. When we compared SAA index with PINI in many diseases, it turned out that SAA index became a more effective index which reflected the patient condition than did PINI. As for this index, it is expected to be used by NST while further alternation may be needed.     

Prevalence of asthma in adults in Menda town rural-mountain area in Japan]

Several reports have suggested that the prevalence of asthma in adults is currently increasing. However, recent prevalence of asthma has not reported in Japan, especially in rural-mountain areas. To investigate the prevalence of asthma in adults in Japan, we conducted clinical epidemiological research on 5066 inhabitants of Menda town, in a rural-mountain area of Japan. The study population comprised 98.7% of adults in the town, including senior high school students whose age were more than 15 years old. The prevalence of asthma among adults was 3.6%. The ratio of prevalence in males to prevalence in females was 1.44. Peaks prevalences were observed in the age ranges of 15-19 and > 70 years old in males, and 15-19, 40-49 and > 70 years old in females.     

Arrangement of D-periodic collagen fibrils and association of proteoglycans with fibrils in the synovium of the mouse temporomandibular joint

The present study was performed to examine changes in the arrangement of D-periodic collagen fibrils in the synovium of the growing temporomandibular joint in mice. At 1 week of age, the mandibular condyle was undeveloped, and only a few collagen fibrils were recognizable in the subintimal layer of the synovium. At 8 weeks, the mandibular condyle was structurally developed with an increase of collagen fibrils in the synovium; a fully mature condyle was observed at 6 months of age. The close association of proteoglycans with collagen fibrils in the synovium of the growing joint was examined by both conventional and energy-filtering transmission electron microscopy of cupromeronic blue-stained specimens. Proteoglycans were associated with D-periodic collagen fibrils in the short filamentous form in random fashion at 1 week of age, but in a regular pattern with D-periodicity at 6 months. These associations in the synovium could be correlated with the mechanical character of the temporomandibular joint.     

The effects in the excess administration of prostaglandin E1 on the indicator enzymes of organella membrane in gastric mucosa

Administration of excess vitamin A to rats causes gastric ulceration. In this study the effects on the gastric mucosa of excess vitamin A and excess prostaglandin E1, alone and in combination, were studied. Prostaglandin E1 protected against ulceration by vitamin A. Vitamin A labilized marker enzymes from four different membrane systems, namely those of the lysosomes, mitochondria, endoplasmic reticulum and plasma membrane, whereas only the effect on lysosomes was prevented by prostaglandin E1. Indeed, the prostaglandin alone labilized the enzymes from plasma membrane and endoplasmic reticulum and also damaged mitochondrial membranes. Both vitamin A and prostaglandin E1 caused a reduction in the total number and an increase in irregularly-shaped mitochondria in the parietal cells and produced dilation of the endoplasmic reticulum in both parietal and chief cells. It is noteworthy that prostaglandin E1 effectively prevents ulceration by vitamin A despite the extent to which it damages these membrane systems. These findings lend support to the hypothesis that vitamin A ulceration of the gastric mucosa is mediated via release of lysosomal enzymes, following damage to the lysosomal membranes.