Hideo Shirafuji

Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma

Airway hyperresponsiveness (AHR), goblet cell metaplasia, and mucus overproduction are important features of bronchial asthma. To elucidate the molecular mechanisms behind these pulmonary pathologies, we examined for genes preferentially expressed in the lungs of a murine model of allergic asthma by using suppression subtractive hybridization (SSH). We identified a gene called gob-5 that had a selective expression pattern in the airway epithelium with AHR. Here, we show that gob-5, a member of the calcium-activated chloride channel family, is a key molecule in the induction of murine asthma. Intratracheal administration of adenovirus-expressing antisense gob-5 RNA into AHR-model mice efficiently suppressed the asthma phenotype, including AHR and mucus overproduction. In contrast, overexpression of gob-5 in airway epithelia by using an adenoviral vector exacerbated the asthma phenotype. Introduction of either gob-5 or hCLCA1, the human counterpart of gob-5, into the human mucoepidermoid cell line NCI-H292 induced mucus production as well as MUC5AC expression. Our results indicated that gob-5 may play a critical role in murine asthma, and its human counterpart hCLCA1 is therefore a potential target for asthma therapy.

Accumulation of Tripeptide Derivatives by Mutants of Cephalosporium acremonium

The two β-lactam antibiotics produced by Cephalosporium acremonium ATCC 14553, cephalosporin C and penicillin N, have been proposed to be biosynthesized through the peptide, δ-(l-α-aminoadipyl)-l-cystemyl-d-valine.Many β-lactam negative mutants were derived from the strain No. 52, which was a more potent producer of the β-lactam antibiotics than the parent strain, C. acremonium ATCC 14553. Some of them were found to accumulate two sulfur-containing peptides. These compounds were isolated from the culture filtrate of one of the mutants, N-2 and determined to be the dimer of δ-(l-α-aminoadipyl)-l-cysteinyl-d-valine and the S-methylthio derivative of the tripeptide.

Induction of interferon and host resistance in vivo by double-stranded complexes of copolyribonucleotide of inosinic and guanylic acids with polyribocytidylic acid

Several double-stranded complexes of copolyribonucleotide of inosinic and guanylic acids with polyribocytidylic acid (poly IG∶C) were found to possess interferon inducing activity stronger than poly I∶Cin vivo, Their activity increased in parallel with increase in the ratio of guanine base to hypoxanthine base in these copolymers as far as double-strand formation was observed with polyribocytidylic acid. Many other combinations of copolyribonucleotide with homopolyribonucleotide were also investigated, and several of them were found to induce interferon. However, the interferon inducing effects of these combinations including complementary base-pairings of hypoxanthine and cytosine increased in parallel with the length of the base-pairings, thus approaching to that of poly I∶C. It is, therefore, supposed that the activity of poly IG∶ C is somewhat different from poly I∶C and that those of other combinations owe to the essential structure of poly I∶C. Furthermore, kinetics of interferon induction, cross tolerance to reinduction, and antiviral effectsin vivo of poly IG∶C and poly I∶C were studied.

Studies on the Guanosine Degrading System in Bacterial Cell:Part III. Purification and Properties of Guanosine Deaminase

A highly purified preparation of the enzyme, guanosine deaminase, has been obtained by a four-step purification procedure from the cells of Pseudomonas convexa No. 149. The enzyme deaminates guanos...