Peptides that block hepatitis B virus assembly: analysis by cryomicroscopy, mutagenesis and transfection

Peptides selected to bind to hepatitis B virus (HBV) core protein block interaction with the long viral surface antigen (L-HBsAg) in vitro. High resolution electron cryomicroscopy showed that one such peptide binds at the tips of the spikes of the core protein shell. The peptides contain two basic residues; changing either of two acidic residues at the spike tip to an alanine greatly reduced the binding affinity. Transfection of hepatoma cells with a replication-competent HBV plasmid gave significantly reduced production of virus in the presence of peptide, in a dose-dependent manner. These experiments show that the interaction of L-HBsAg with core particles is critical for HBV assembly, and give proof of principle for its disruption in vivo by small molecules.     

The effects of local hyperthermia on the catabolism of a radioiodinated chimeric monoclonal antibody

Local hyperthermia has been shown to increase the tumor uptake and tumor:normal tissue ratios of radiolabeled monoclonal antibodies (mAbs) in athymic mouse xenograft models. The current study was undertaken to determine whether this behavior was related in part to alterations in mAb catabolism by local hyperthermia. Human/mouse chimeric 81C6 mAb reactive with tenascin and a nonspecific control mAb were labeled with 125I using Iodo-Gen and given to separate groups of athymic mice bearing s.c. D-54 MG human glioma xenografts. Half of the animals were then subjected to 4-h tumor-localized hyperthermia at 41.8 degrees C, a protocol previously shown to enhance the specific tumor uptake of the mAb in this xenograft model. The tumor, serum, liver, kidney, and urine were collected from heated as well as control animals 4 and 24 h after injection of the mAb and analyzed by SDS-PAGE and trichloroacetic acid precipitation. At 24 h, a significantly higher percentage of 81C6 was present as intact mAb in the tumors harvested from heated animals compared with those from controls. Unexpectedly, intact mAb was found in the urine of mice immediately after hyperthermia, but not in unheated control animals. We conclude that local hyperthermia decreases the catabolism of the mAb in the tumor and increases the urinary excretion of the mAb through a transient increase in glomerular permeability.     

Reversal of the morphological effects of monocular deprivation in the kittens's lateral geniculate nucleus

1. Eleven kittens were deprived of vision in one eye until the age of between 5 and 14 weeks. Their eyes were then reverse-sutured, they were allowed to survive for a further 3-63 days, and their brains were then examined histologically. 2. Measurement of the cross-sectional area of cells in the lateral geniculate nucleus (LGN) showed that when the reversal of lid suture was performed at the age of 8 or 14 weeks, the mean cell size was smaller in laminae connected to the initially closed right eye than it was in other laminae. 3. When the reversal of lid suture took place at 5 or 6 weeks of age there was a reversal of interlaminar size differences: the initially deprived eye was then connected to laminae containing larger cells. Even within 3 days after the reversal of lid suture, most of the morphological effects of the initial suture had been abolished, and they were fully reversed within 12 days. 4. These results are compared with physiological changes in the visual cortex of these and similarly reared animals.     

Systemic calciphylaxis revisited

A syndrome characterized by rapidly progressive ischemic necrosis involving large areas of the skin and muscle, and by peripheral gangrene associated with extensive vascular calcifications was observed in a patient with end-stage renal failure on chronic hemodialysis. In an effort to control the disease, parathyroidectomy was performed which resulted in rapid improvement of tissue perfusion. However, the patient eventually died from sepsis within 2 months after admission. This case presents the typical features of the syndrome of systemic calciphylaxis. The literature is reviewed searching for similar cases of this poorly recognized, but life-threatening, clinical syndrome. The pathogenesis, clinical manifestations, and therapy of this unusual and rapidly progressive, but potentially reversible, condition are reviewed with emphasis on its prompt recognition and appropriate management.