Effect of myasthenic IgG on degradation of junctional acetylcholine receptor

We investigated the effect of the lgG from patients with myasthenia gravis (MG) on the degradation of normal rat junctional acetylcholine receptor (AChR) labeled with ¹²⁵l-α-bungarotoxin (BuTx) and calculated the degradation rate (DR). The DR for the lgG from these patients was significantly higher than that from healthy volunteers and patients with other autoimmune diseases. For MG, DR was significantly correlated with the severity of the disease but not with anti-AChR antibody titer. DR was accelerated by lgG from patients with generalized MG whose antibody titers were in the normal range and by lgG from patients with ocular MG. These results indicate that measurement of the DR of junctional AChR in normal rats is more closely correlated with the severity of the disease than is measurement of anti-AChR antibody and that the former is a sensitive and confirmatory method for evaluating MG. © 1993 John Wiley & Sons, Inc.     

Specific [125I]brain natriuretic peptide-26 binding sites in rat and pig kidneys

Specific binding sites for porcine brain natriuretic peptide-26 (BNP-26), a member of the atrial natriuretic peptide family (ANPs), were investigated in the kidney by using receptor autoradiographic and membrane binding techniques with [125I]BNP-26. The binding sites were discretely localized in rat and porcine kidney areas corresponding anatomically to the glomeruli and inner medulla. There were no differences between the localization of [125I]BNP-26 and [125I]alpha-rat ANP binding sites in the kidney. [125I]BNP-26 binding to solubilized membranes from isolated glomeruli of the rat kidney was saturable, and a single class of high-affinity sites was labeled with a KD of 372 pM. The radioligand bound to two sites in solubilized inner medullary membranes of the rat, a low-affinity site with a KD of 30 nM, and a high-affinity site with a KD of 33 pM. The rank order of potency to inhibit binding was BNP-26 = alpha-rat ANP-(1-28) greater than atriopeptin III (ANP-(103-126)) much greater than atriopeptin I (ANP-(103-123)) greater than des-Cys105,Cys121- ANP-(104-126). Thus, [125I]BNP-26 presumably recognizes ANP receptors in the kidney. The possibility that BNP-26 regulates, as a circulating hormone, kidney functions by binding to ANP receptors would have to be considered.     

Macrophage inflammatory protein 3alpha-CC chemokine receptor 6 interactions play an important role in CD4+ T-cell accumulation in periodontal diseased tissue

The regulatory role of chemokines and chemokine receptors on specific lymphocyte recruitment into periodontal diseased tissue is poorly characterized. We observed that lymphocytes infiltrating inflamed gingival tissue expressed marked levels of CCR6. In periodontal diseased tissue, the expression of MIP-3alpha mRNA was detected by RT-PCR and further, MIP-3alpha was distributed in the basal layer of gingival epithelial cells, microvascular endothelial cells and the areas of inflammatory cells as shown by immunohistochemistry. Moreover, CCR6-expressing cells infiltrated into periodontal diseased tissue, and the proportion of CCR6-positive CD4+ T cells was significantly elevated in periodontal diseased tissue compared with peripheral blood in the same patients. Furthermore, gingival lymphocytes isolated from patients showed migration toward MIP-3alpha in an in vitro chemotaxis assay in which migration was abrogated by specific antibody to CCR6. Thus, these findings suggested that CCR6 and the corresponding chemokine, MIP-3alpha may have an important regulatory role in specific lymphocyte migration into inflamed periodontal tissue.     

Chymase participates in chronic dermatitis by inducing eosinophil infiltration

An epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) to a mouse ear caused a transient skin swelling, and the repetition of the challenge enlarged the contact dermatitis. The repeated challenge with DNFB also induced eosinophil infiltration on the application site. Administration of a chymase inhibitor significantly inhibited the ear swelling as well as eosinophil accumulation. An intradermal injection of human chymase to the mouse ear also elicited transient skin swelling and eosinophil infiltration, both of which were augmented in proportion to the number of injections. Human serum albumin and heat-inactivated chymase failed to induce such skin reactions, suggesting the participation of proteolytic activity of the enzyme. In addition, chymase stimulated eosinophil migration in vitro in a concentration-dependent manner. Taken together, these observations suggest that mast cell chymase may contribute to development of the DNFB-induced dermatitis, probably by promoting eosinophil infiltration. It is therefore possible that chymase plays a role in pathogenesis of chronic dermatitis such as atopic dermatitis.     

Intercellular adhesion molecule-1 in patients with idiopathic interstitial pneumonia

This study focuses on a possible role of intercellular adhesion molecule-1 (ICAM-1) in interstitial pulmonary diseases. We determined a soluble form of ICAM-1 in serum and bronchoalveolar lavage fluid (BALF) using ELISA in patients with usual interstitial pneumonia (UIP), bronchiolitis obliterance organizing pneumonia (BOOP), or nonspecific interstitial pneumonia (NSIP). In addition, we investigated the expression of ICAM-1 in the lung tissues of these patients by means of immunohistochemical staining. Serum levels of soluble ICAM-1 were significantly higher in patients with UIP or NSIP than in healthy subjects, and were also high in patients with BOOP. The soluble ICAM-1 in BALF tended to be higher in patients with UIP, BOOP, or NSIP than in normal subjects. A significant correlation was seen between soluble levels of ICAM-1 in serum and BALF. In the immunostaining of ICAM-1 of the lung tissues, ICAM-1 expression was more pronounced in patients with UIP than in those with BOOP or NSIP. The increased expression of ICAM-1 was seen in type II alveolar epithelium and vascular endothelium in patients with interstitial pneumonia. A positive correlation was observed between the degree of ICAM-1 expression in the lung tissues and the BALF levels of soluble ICAM-1. The expression of ICAM-1 in type II alveolar epithelium suggests that ICAM-1 plays a specific role in the fibrotic process of the lung, and that the measurement of soluble ICAM-1 in sera and BALF could be a useful marker for evaluating the progression of fibrosis.     

Comparison of adult height between patients with XX and XY gonadal dysgenesis: support for a Y specific growth gene(s).

Adult height was compared between published cases of patients with XX gonadal dysgenesis (XXGD) and those with XY gonadal dysgenesis (XYGD). The mean adult height of XYGD patients (171.0 cm (SD 7.8), n = 27) was significantly greater than that of XXGD patients (164.4 cm (7.7), n = 27) (p less than 0.01). This finding supports the existence of a Y specific growth gene(s) which promotes statural growth independently of the effects of gonadal sex steroids.     

C to T transition at the first nucleotide of codon 63 of the β-globin gene corresponding to hemoglobin M-Saskatoon in an Indonesian boy

Summary Hemoglobin (Hb) M-Saskatoon, a variant of methemoglobin, is characterized by mild hemolysis. It is caused by the substitution of a histidine by a tyrosine at the 63rd amino acid residue of the -globin chain. Amplification and sequence analysis of genomic -globin DNA from an Indonesian boy diagnosed as having the more severe disease thalasemia demonstrated the presence of a C to T transition at nucleotide 473 in one of the two -blogin genes resulting in a histidine to tyrosine substitution at 63rd residue. This amino acid change matched with that reported in Hb M-Saskatoon. This nucleotide change abolished a recognition site for the restriction endonucleaseNlaIII.NalIII digestion of the corresponding -globin DNA amplified from the patient's parents indicated that the mutation was inherited through from his mother. This result shows that the world-wide distribution of Hb M-Saskatoon extends to Indonesia, where it was not previously identified. Possible causes of the unusually severe symptoms observed in the case are discussed.