Production of functional chimaeric mouse/human antibody

The availability of monoclonal antibodies has revived interest in immunotherapy. The ability to influence an individual's immune state by administering immunoglobulin of the appropriate specificity may provide a powerful approach to disease control and prevention. Compared with immunoglobulin from other species, human immunoglobulin (Ig) might be best for such therapeutic intervention; it might function better with the recipient's effector cells and should itself be less immunogenic. The success of the mouse hybridoma system suggests that immunoglobulin of virtually any specificity can be obtained from a properly immunized animal. In the human system, however, immunization protocols are restricted by ethical considerations, and it is not yet clear whether human antibody-producing cell lines of the required specificity can be obtained from adventitiously immunized individuals or from in vitro immunized cells. A method which might circumvent these difficulties is to produce antibodies consisting of mouse variable regions joined to human constant regions. Therefore, we have constructed immunoglobulin genes in which the DNA segments encoding mouse variable regions specific for the hapten trinitrophenyl (TNP) are joined to segments encoding human mu and kappa constant regions. These 'chimaeric' genes are expressed as functional TNP-binding chimaeric IgM. We report here some of the properties of this novel IgM.     

Reduced bactericidal capacity of polymorphonuclear leucocytes in nephrotic syndrome and effect of steroid therapy

Zusammenfassung Es wird der Nachweis erbracht, dass die bakterizide Wirkung der polymorph-kernigen Leukozyten bei Patienten mit nephrotischem Syndrom vermindert ist und dass Prednisolon einen günstigen Einfluss auf die Bakterizidie polymorph-kerniger Leukozyten beim nephrotischen Syndrom hat.     

Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae

The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation.     

The occurrence of nerve growth factor in teleost fishes

Résumé Le «nerve growth factor» a été découvert dans les axes spinaux de quelques poissons lors d'un essai biologique, in vitro, provoquant la croissance de fibres nerveuses des ganglia spinaux des embryons de poulet.     

Transfer of a cloned immunoglobulin light-chain gene to mutant hybridoma cells restores specific antibody production

The expression of immunoglobulin (Ig) genes is regulated at several levels. For example, although kappa-chain production requires a DNA rearrangement that juxtaposes variable and joining segments, this rearrangement is not sufficient for kappa-chain gene expression; that is, some cell types do not permit immunoglobulin production. The mechanisms responsible for the regulation of the expression of rearranged immunoglobulin genes are poorly understood. The technique of modifying cloned genes in vitro and transferring the modified genes to cells in culture provides a tool for identifying the structural features required for gene expression. To analyse immunoglobulin genes in this manner, however, it is first necessary to use, as recipients, cells that normally permit immunoglobulin production. We report here that a cloned kappa-chain gene is expressed in immunoglobulin-producing hybridoma cells. Furthermore, the product of the transferred kappa-chain gene is capable of restoring specific antibody production to the transformed cells.     

The ELF4 gene controls circadian rhythms and flowering time in Arabidopsis thaliana

Many plants use day length as an environmental cue to ensure proper timing of the switch from vegetative to reproductive growth. Day-length sensing involves an interaction between the relative length of day and night, and endogenous rhythms that are controlled by the plant circadian clock. Thus, plants with defects in circadian regulation cannot properly regulate the timing of the floral transition. Here we describe the gene EARLY FLOWERING 4 (ELF4), which is involved in photoperiod perception and circadian regulation. ELF4 promotes clock accuracy and is required for sustained rhythms in the absence of daily light/dark cycles. elf4 mutants show attenuated expression of CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), a gene that is thought to function as a central oscillator component. In addition, elf4 plants transiently show output rhythms with highly variable period lengths before becoming arrhythmic. Mutations in elf4 result in early flowering in non-inductive photoperiods, which is probably caused by elevated amounts of CONSTANS (CO), a gene that promotes floral induction.