Antibody combining site: the B polypeptide chain

The antibody molecule consists of several polypeptide chains. Peptides, which appear to have been derived from the binding region of the rabbitantibody molecule directed against pazobenzenearsonate, have been isolated. The particular polypeptide chain from which these peptides are derived has now been identified as the B chain described by Fleischman, Pain, and Porter.     

Abortive initiation and productive initiation by RNA polymerase involve DNA scrunching

Using single-molecule DNA nanomanipulation, we show that abortive initiation involves DNA "scrunching"--in which RNA polymerase (RNAP) remains stationary and unwinds and pulls downstream DNA into itself--and that scrunching requires RNA synthesis and depends on RNA length. We show further that promoter escape involves scrunching, and that scrunching occurs in most or all instances of promoter escape. Our results support the existence of an obligatory stressed intermediate, with approximately one turn of additional DNA unwinding, in escape and are consistent with the proposal that stress in this intermediate provides the driving force to break RNAP-promoter and RNAP-initiation-factor interactions in escape.     

Antibody formation: stimulation by polyadenylic and polycytidylic acids

Complexes of polyadenylic and polyuridylic acids, or of polycytidylic acid and methylated bovine serum albumin, enhance the early rate of increase in numbers of antibody-forming spleen cells in mice immunized with sheep red blood cells or other particulate antigens. Polyadenylic and polycytidylic acids, respectively, appear to be the source of the critical stimulators which, as demonstrated by others in bacteria, may act by influencing nucleotide kinase activity. The stimulated antibody response, but not the normal response, is antagonized by kinetin riboside and by an adenosine derivative occurring in sRNA.     

Hypersensitivity to a synthetic polypeptide: induction of a delayed reaction

A multichain copolypeptide, p(Tyr,Glu)-pAla--pLys, induced in guinea pigs a prolonged state of delayed hypersensitivity not associated with detectable circulating antibodies. Cross reactions of the delayed type were observed with chemically related polypeptides.     

Herpetic keratoconjunctivitis: therapy with synthetic double-stranded RNA

A study was undertaken in rabbits to determine how late in the course of keratoconjunctivitis caused by herpes simplex recovery could be effected by an inducer of interferon. Interferon was induced by means of synthetic double-stranded RNA copolymer formed with polynosinic acid: polycytidilic acid RNA. Therapy promotes recovery from severe and fully established keratoconjunctivitis for which treatment was begun as late as 3 days after virus inoculation. No drug toxicity was observed in the therapeutic dose range. These findings further support the proposed role of the interferon mechanism in the natural recovery of already established viral infection. They also suggest the usefulness of interferon inducers in viral infections of man.     

Antibody to leukemia virus: widespread occurrence in inbred mice

Mice from a wide variety of inbred strains produce immunoglobulin G antibody against murine leukemia virus. This is contrary to the common view that the mouse is immunologically tolerant to its endogenous leukemia virus.     

小鼠鼻粘膜接种伤寒杆菌Fe-SOD的抗体应答

目的：观察小鼠鼻腔接种伤寒杆菌的Fe—SOD后血液和粘膜系统的抗体应答。方法：用IL-1作为佐剂,将伤寒杆菌的Fe—SOD经鼻腔接种小鼠,检测小鼠血液及肠液中的抗体应答。结果：当用IL-1作为佐剂时,经鼻腔接种伤寒杆菌Fe—SOD的小鼠血液和肠液中可产生高水平特异性IgG和IgA类抗体;而腹腔注射仅在血液中产生高水平特异性IgG抗体。结论：用IL-1作为佐剂,伤寒杆菌Fe—SOD经鼻腔接种后可引起小鼠粘膜系统和血液中的抗体应答。     

Efficient initiation of HCV RNA replication in cell culture

Hepatitis C virus (HCV) infection is a global health problem affecting an estimated 170 million individuals worldwide. We report the identification of multiple independent adaptive mutations that cluster in the HCV nonstructural protein NS5A and confer increased replicative ability in vitro. Among these adaptive mutations were a single amino acid substitution that allowed HCV RNA replication in 10% of transfected hepatoma cells and a deletion of 47 amino acids encompassing the interferon (IFN) sensitivity determining region (ISDR). Independent of the ISDR, IFN-alpha rapidly inhibited HCV RNA replication in vitro. This work establishes a robust, cell-based system for genetic and functional analyses of HCV replication.     

Lymphocytic choriomeningitis: production of antibody by "tolerant" infected mice

Newborn mice infected with lymphocytic choriomeningitis virus are not immunologically tolerant to the agent but, rather, appear to make antibody to the virus. This antibody was detectable only in the kidneys, where presumably it had been deposited in the glomeruli in the form of complexes of antibody, virus, and complement.     

Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice

When rodents are infected with the nematode Nippostrongylus brasiliensis, large numbers of eosinophils appear in their blood and lungs and their serum immunoglobulin E (IgE) is increased. Injection of a monoclonal antibody to interleukin-5 completely suppressed the blood eosinophilia and the infiltration of eosinophils in the lungs of parasitized mice but had no effect on serum IgE. In contrast, an antibody to interleukin-4 inhibited parasite-induced IgE but not the eosinophilia. These results show that interleukin-5 is important in eosinophil production in vivo and that IgE and eosinophil production are regulated by different cytokines produced by the TH2 subset of CD4-expressing T cells.     

Suppression of macrophage activation and T-lymphocyte function in hypoprolactinemic mice

The effects of prolactin on lactation and reproductive organs are well known. However, the other possible target organs and physiological consequences of altered levels of circulating prolactin remain poorly understood. In this study, mice were treated with bromocryptine, a dopamine receptor agonist that inhibits pituitary prolactin secretion. Bromocryptine treatment prevented T-cell-dependent induction of macrophage tumoricidal activity after the intraperitoneal injection of Listeria monocytogenes or Mycobacterium bovis. Coincident treatment with ovine prolactin reversed this effect. Of the multiple events leading to macrophage activation in vivo, the production by T-lymphocytes of gamma-interferon was the most impaired in bromocryptine-treated mice. Lymphocyte proliferation after stimulation with mitogens in vitro was also depressed in spleens of bromocryptine-treated mice, and coadministration of prolactin also reversed this effect. Bromocryptine treatment also reduced the number of deaths resulting from inoculation of mice with Listeria; exogenous prolactin significantly reversed this effect. The critical influence of pituitary prolactin release on maintenance of lymphocyte function and on lymphokine-dependent macrophage activation suggests that, in mice, lymphocytes are an important target tissue for circulating prolactin.     

Protein displacement by DExH/D "RNA helicases" without duplex unwinding

Members of the DExH/D superfamily of nucleic acid-activated nucleotide triphosphatases are essential for virtually all aspects of RNA metabolism, including pre-messenger RNA splicing, RNA interference, translation, and nucleocytoplasmic trafficking. Physiological substrates for these enzymes are thought to be regions of double-stranded RNA, because several DExH/D proteins catalyze strand separation in vitro. These "RNA helicases" can also disrupt RNA-protein interactions, but it is unclear whether this activity is coupled to duplex unwinding. Here we demonstrate that two unrelated DExH/D proteins catalyze protein displacement independently of duplex unwinding. Therefore, the essential functions of DExH/D proteins are not confined to RNA duplexes but can be exerted on a wide range of ribonucleoprotein substrates.     

Modeling the initiation and progression of human acute leukemia in mice

Our understanding of leukemia development and progression has been hampered by the lack of in vivo models in which disease is initiated from primary human hematopoietic cells. We showed that upon transplantation into immunodeficient mice, primitive human hematopoietic cells expressing a mixed-lineage leukemia (MLL) fusion gene generated myeloid or lymphoid acute leukemias, with features that recapitulated human diseases. Analysis of serially transplanted mice revealed that the disease is sustained by leukemia-initiating cells (L-ICs) that have evolved over time from a primitive cell type with a germline immunoglobulin heavy chain (IgH) gene configuration to a cell type containing rearranged IgH genes. The L-ICs retained both myeloid and lymphoid lineage potential and remained responsive to microenvironmental cues. The properties of these cells provide a biological basis for several clinical hallmarks of MLL leukemias.     

Pituitary tumors in mice after prolonged feeding of synthetic progestins

An enhanced development of pituitary tumors was observed in virgin female mice of the C57 Leaden strain following repeated oral administration of synthetic progestins. This finding appears to parallel the co-carcinogenic enhancement of mammary tumor development elicited in C3H mice treated repeatedly with progesterone.     

Cerebral acid hydrolase activities: comparison in "quaking" and normal mice

The activity of several acid hydrolase enzymes was determined in whole brain homogenates of adult "quaking" and normal mice. A striking decrease was found in alpha-mannosidase and, to a lesser extent, aryl sulfatase levels in the samples from the mutant animals. The activities of the other "lyso-somal" enzymes were only slightly lowered.     

"Intrinsic" immunological tolerance in allophenic mice

Mice experimentally derived from pairs of conjoined, undifferentiated, cleavage-stage embryos of different histocompatibility genotypes can retain cells of each strain, which still produce their characteristic antigenic products. The animals are permanently tolerant of cells of both original types, remain free of runt disease, and display a normal and specific immune response to introduction of a foreign antigen. Absence of autoimmunity in development of ordinary animals is explainable by the "intrinsic" kind of tolerance found here.     

Antibody formation in nonimmune mouse peritoneal cells after incubation in gum containing antigen

Peritoneal cells from normal mice in a semisolid medium containing sheep erythrocytes were incubated at 37 degrees C for 2 or 3 days. During this period, hemolytic antibodies developed spontaneously. Arguments are presented that true de novo synthesis of antibody has taken place in previously uncommitted cells.