Establishment of monoclonal antibodies broadly neutralize infection of hepatitis B virus.

Antibodies against hepatitis B virus S protein can protect against hepatitis B virus (HBV) infection. Therefore, hepatitis B immunoglobulin (HBIG), which contains HBsAb, is used clinically as a therapy for HBV infection. In this study, a series of monoclonal antibodies that recognize multiple HBV genotypes was obtained. All the antibodies recognized conformational epitopes of S protein, but not linear epitopes. Several antibodies neutralized HBV infection and exhibited strong affinities and neutralizing activities. Antigenic epitope analysis demonstrated that they recognized residue Ile152 of S protein, which is localized outside the "a" determinant. Ile152 is highly conserved, and a mutation in this residue resulted in reduced expression of large hepatitis B surface proteins (L protein), suggesting that the amino acid at this position is involved in the expression of L protein. In addition, the antibodies neutralized the infection of hepatitis D virus possessing a Gly145 mutation to Arg in S protein, which is a well-known escape mutation against HBIG treatment. Using mouse monoclonal antibodies, a humanized antibody possessing affinities and neutralizing activities similar to those of the original mouse antibody was successfully established. The antibodies generated in this study may have the potential for use in alternative antibody therapies for HBV infection.

Conformation of poly(γ-glutamic acid) in aqueous solution.

Local conformation and overall conformation of poly(γ-DL-glutamic acid) (PγDLGA) and poly(γ-L-glutamic acid) (PγLGA) in aqueous solution was studied as a function of degree of ionization ε by (1) H-NMR, circular dichroism, and potentiometric titration. It was clarified that their local conformation is represented by random coil over an entire ε range and their overall conformation is represented by expanded random-coil in a range of ε > ε(*) , where ε(*) is about 0.3, 0.35, 0.45, and 0.5 for added-salt concentration of 0.02M, 0.05M, 0.1M, and 0.2M, respectively. In a range of ε < ε(*) , however, ε dependence of their overall conformation is significantly differentiated from each other. PγDLGA tends to aggregate intramolecularly and/or intermolecularly with decreasing ε, but PγLGA still behaves as expanded random-coil. It is speculated that spatial arrangement of adjacent carboxyl groups along the backbone chain essentially affects the overall conformation of PγGA in acidic media.

A familial case of multiple recurrent cardiac myxomas.

The familial variant of cardiac myxomas is an autosomally dominant disease. Here, we report a case of recurrent multiple cardiac myxomas wherein the patient, a 36-year-old woman who was referred for palpitations and nocturnal dyspnea, had a relevant familial history. Her mother had undergone extirpation of cardiac myxoma when she was about 50 years old. Echocardiography showed the presence of multiple cardiac myxomas. One of the cardiac myxomas nearly obstructed the left ventricular inflow; therefore, we extirpated the myxomas under cardiopulmonary bypass and cardioplegic arrest. The operation was uneventful and the postoperative clinical course was good. Pathological examination confirmed that the extirpated mass was a myxoma. Approximately 3 years after the first cardiac operation, we found a recurrent cardiac myxoma in the same patient. She then underwent a second operation and was discharged without any complications. Pathological examination also confirmed that the cardiac mass was a myxoma and that there was no malignancy. .