Subpopulations of lymphocytes in portal areas, especially infiltrating bile duct epithelia were analyzed by light and electron microscopy using indirect peroxidase-labeled antibody method and monoclonal antibodies against pan-T (Leu 1), cytotoxic/suppressor T (Leu 2a), helper/inducer T (Leu 3a) and natural killer/K (Leu 7) and suppressor T (Leu 15) cells in liver biopsy specimens from four patients with primary biliary cirrhosis. Bile ducts with chronic nonsuppurative destructive cholangitis were observed in two patients. Leu 1+ and Leu 2+ cells were frequently seen in intimate contact with epithelial ductal cells. The majority of intraepithelial cells possessing Leu 2a antigen did not react with anti-Leu 15 antibody. Leu 3a+ or Leu 7+ cells seldom infiltrated ductal epithelia. These findings indicate that the majority of intraepithelial lymphocytes in bile ducts most likely represent Leu 2a+15- cytotoxic T cells. By immunoelectron microscopy, Leu 1+ or Leu 2a+ lymphocytes often breached the basement membrane of bile ducts and were present within dilated intercellular spaces between biliary epithelial cells. Furthermore, they often formed sharp or broad contacts with the epithelial cells, and occasionally pseudopods projecting from the surfaces of Leu 2a+ cells extended into the epithelial cells. Most of Leu 2a+ lymphocytes contained little cytoplasm with few granules and a small Golgi apparatus. Such findings suggest that cytotoxic T cells may contribute to the pathogenesis of chronic nonsuppurative destructive cholangitis in primary biliary cirrhosis.

Adult↗

PubMedDate not supplied

Microphthalmia (mi) mice display an aberrant bone trace element composition.

It has been recognized that bone trace element composition analysis provides clues when analyzing bone-related physiological conditions. Increasing numbers of bone-related genetic diseases have been identified recently. In this study, we have analyzed bone trace element composition in a genetic mutant animal model. Mutations in the mouse microphthalmia (mi) gene affect the development of a number of cell types, including melanocytes, mast cells, and osteoclasts. Previous studies have shown that different alleles of the mi locus show osteopetrosis. In order to gain insights into the effects of a particular genetic defect on bone trace element composition and bone structure, we performed bone trace element composition analysis using inductively coupled plasma atomic emissions spectrometry (ICP-AES). Marked changes in bone trace element levels were found in vertebrate bones of mi mutant mice. The implications and possible applications of bone trace element analysis will be discussed in this article.

Animals↗

PubMedDate not supplied

Effect of a moderately energy-restricted diet on obese patients with fatty liver.

The effects of a moderately energy-restricted (25 kcal/kg) diet on liver-function tests, anthropometric measurements, mononuclear-cell phospholipid fatty acid, lymphocyte blastogenesis, and plasma prostaglandin E2 and alpha-tocopherol levels were observed at weeks 0, 8, and 24 in 14 obese patients with fatty liver. Serum aminotransferase levels were improved significantly, with decreases in the body mass index and waist circumference. Decreases in energy intake from carbohydrate and increases in intake of vitamin A, vitamin C, and vegetables were observed at week 24. In mononuclear-cell phospholipids, linoleic acid (18:2omega 6), which was significantly lower in patients than in controls at week 0, was increased at week 24. In contrast, arachidonic acid was decreased. Plasma prostaglandin E2 levels were significantly lower in patients than in controls at week 0 and increased at week 24. The mononuclear-cell response for phytohemagglutinin correlated with 18:2omega 6 in mononuclear-cell phospholipids (r = 0.692, P < 0.01). Improvement of the serum alanine-aminotransferase level correlated with an increase in the plasma alpha-tocopherol level (r = -0.667, P < 0.01) and increases in consumption of vitamin A, omega 3 polyunsaturated fatty acids, and vegetables. These findings suggest that a hypoenergetic diet rich in omega 3 polyunsaturated fatty acids and antioxidants might be beneficial for obese patients with fatty liver.

Adult↗

PubMedDate not supplied

Unique structure of murine interleukin-2 as deduced from cloned cDNAs.

Interleukin-2 (IL-2) is a lymphokine originally described as a humoral factor required for the continued proliferation of activated T-cell clones. It also seems to be involved in the mitogenic response of thymocytes, in augmenting natural killer cell activity, in the generation of cytotoxic T cells and in the induction of other lymphokines such as gamma-interferon and a B-cell growth factor (BCGF-1). More recently, there has been evidence for the involvement of IL-2 per se in the stimulation of B-cell growth (ref. 10 and T. Kishimoto and J. Vilcek, personal communications). We have reported previously the cloning and expression of a human IL-2 complementary DNA. The cDNA encodes biologically active IL-2 which would consist of 153 amino acids, including a signal sequence. Because so much of the work on IL-2 has been done in the human and mouse, we sought to obtain cDNA encoding murine IL-2, and we now report the cloning, expression and sequence analysis of murine IL-2 cDNAs. The longest cDNA insert encodes a polypeptide of 169 amino acids, containing unique repeats of a CAG sequence which would encode 12 consecutive glutamine residues within the active IL-2 molecule.

Amino Acid Sequence↗

PubMedDate not supplied

Reconstitution of functional receptor for human interleukin-2 in mouse cells.

Interleukin-2 (IL-2) has a key role in the antigen-specific clonal growth of T lymphocytes, by virtue of its interaction with a specific cell-surface receptor (IL-2R). The growth signal seems to be delivered by IL-2 bound to the high-affinity, but not the low-affinity, receptor. Genes encoding IL-2 and its receptor (that is, Tac-antigen) have been cloned and analysed in detail. We have now achieved cell-type-specific reconstitution of the high-affinity human IL-2R by expressing the complementary DNA cloned from normal lymphocytes. A mouse T-lymphocytic line, EL-4, expressed human IL-2R with high (dissociation constant (Kd) = 160-220 pM) and low (Kd = 2.1-2.2 nM) affinity for recombinant human IL-2, while mouse L929 cells expressed only a single class of the IL-2R with lower affinity (Kd = 34.5 nM) for the ligand. We also show that the human IL-2R expressed in EL-4 cells responds to IL-2 and mediates reversed signal transduction: growth of the EL-4 cells harbouring the IL-2R is inhibited specifically by human recombinant IL-2. The approach described here may provide a general experimental framework for elucidating the molecular basis of signal transduction mediated by specific receptor-ligand interaction.

Animals↗

PubMedDate not supplied

Epidemiology of genotypes of hepatitis C virus in Japanese patients with type C chronic liver diseases: a multi-institution analysis.

Sixteen medical institutions in Japan collaborated in this study of the epidemiology of hepatitis C virus (HCV) genotypes. A total of 4176 patients with type C chronic liver disease, from the four main islands of Japan, were evaluated. Of those evaluated, 2794 had chronic hepatitis, 727 had liver cirrhosis and 655 had hepatocellular carcinoma. The HCV genotype of the patients was determined by an enzyme-linked immunosorbent assay based on serological genotype 1- and 2-specific recombinant peptides (SG-1 and SG-2, respectively) of the NS4 region. The prevalence of SG-1 and SG-2 HCV was similar in the four main islands of Japan. SG-1 HCV predominated in each disease category (69-76%). The percentage of patients with SG-1 HCV increased by 7%, while that of patients with SG-2 HCV decreased by 7%, as liver disease progressed in severity from chronic hepatitis to carcinoma (P < 0.001). Patients with either SG-1 or SG-2 had a similar mean age and history of blood transfusion. In conclusion, SG-1 HCV was found to predominate in Japan, and the HCV genotype was found to be related to the stage of hepatitis C disease.

Adolescent↗