Generation and characterization of a human monoclonal antibody that neutralizes diverse HIV-1 isolates in vitro.

OBJECTIVE: The purpose of this study was to develop and characterize human monoclonal antibodies (HuMAb) that neutralize HIV-1. DESIGN: Based upon previous studies involving the generation of HuMAb that neutralize other enveloped viruses, we thought it feasible to generate HuMAb that might neutralize HIV-1. METHODS: A HuMAb was generated by fusing splenic B-cells from an HIV-positive patient with a mouse myeloma cell line. Flow cytometry was used to determine surface reactivity of the HuMAb on HIV-infected and non-infected cells. Radioimmunoprecipitation was employed to elucidate the antigen recognized by the HuMAb. A cell survival assay was used to determine the ability of the HuMAb to neutralize divergent isolates of HIV-1 in the presence or absence of complement. A gp120-CD4 inhibition enzyme-linked immunosorbent assay (ELISA) was developed in order to initiate studies to determine the mechanism of neutralization by the HuMAb. RESULTS: An anti-HIV HuMAb was generated that neutralized two HIV-1 isolates (IIIB and MN) without complement and which neutralized one divergent isolate (RF) and one clinical isolate in the presence of complement. This HuMAb, designated S1-1, was found, by flow cytometric analysis, to react with the surface of HIV-1-infected but not with uninfected cells. Radioimmunoprecipitation analysis demonstrated that S1-1 binds to native HIV gp120, but not dithiothreitol (DTT)-treated gp120. In addition, HuMAb S1-1 did not bind to denatured HIV antigens in Western blot analysis. HuMAb S1-1 effectively inhibited the binding of gp120 to soluble CD4 in ELISA. CONCLUSIONS: These results suggest that the epitope recognized by S1-1 is conformational and conserved among diverse HIV-1 isolates and may represent an uncharacterized HIV neutralizing domain within or close to the CD4 binding domain on gp120. HuMAb S1-1 might have a role to play in vaccine development or passive immunotherapy.     

The role of gallium 67 imaging in non-Hodgkin's lymphoma of the gastrointestinal tract

To evaluate the clinical usefulness of gallium 67 imaging in the detection of gastrointestinal (GI) non-Hodgkin's lymphoma (NHL) and in the assessment of the therapeutic effects, images were reviewed in 24 cases (25 lesions: stomach, 20; ileum, 2; and terminal ileum and/or cecum, 3) and were compared using barium studies and, in 16 cases, computerized tomography (CT). In all, 23 (92.0%) of the 25 lesions were detected by⁶⁷Ga citrate imaging, the barium studies detected all 25, and CT detected 15 of 16 lesions (93.8%). The two lesions not identified by imaging and the one not found by CT were the smallest of all. In 2 (8.7%) of the 23 lesions positively identified by⁶⁷Ga-citrate imaging, both CT and imaging revealed the extent of the tumor more accurately than did the barium studies. In all but one of the patients, a close correlation existed between the imaging results and the therapeutic effects. These data suggest that⁶⁷Ga imaging is useful in conjunction with CT and barium studies for the detection of GI NHL and for the assessment of both the spatial extent of disease and the therapeutic effects, although a lack of⁶⁷Ga uptake after therapy does not always indicate a good therapeutic effect.     

Surgical treatment of native valve endocarditis]

Twenty eight patients with native valve endocarditis (NVE) were subjected to this study. Thirteen patients underwent an operation at the chronic phase, and 15 patients at the active phase. One of the 13 patients at the chronic phase died of cardiac rupture due to myocardial infarction which had occurred preoperatively, and one of 10 patients at active phase without annular infection died of rupture of mycotic cerebral aneurysm early postoperatively. Among 5 patients at the active phase with annular infection, prosthetic valve endocarditis occurred in one patient 1.5 months after supraannular aortic valve replacement, and the second operation with a translocation technique was needed. This patient was lost from low output syndrome. Another patient in this group, who underwent a translocation technique because of mycotic annular abscess, died of intestinal infarction late postoperatively. The other 24 patients went a good postoperative course. Five patients with annular infection at the active phase had a shorter duration from the infectious onset to operation (20 days to 2 months, average 38 days), and the causative microorganisms were streptococcus faecalis, staphylococcus epidermidis and gram-negative coccus. One patient, who died of mycotic cerebral aneurysmal rupture, had candida albicans as a causative microorganism. For patients with NVE, an early aggressive operation is essential before infection extends to the annulus or to other vital organs, especially when these microorganisms are identified.     

Cinatrins, a novel family of phospholipase A2 inhibitors. I. Taxonomy and fermentation of the producing culture; isolation and structures of cinatrins.

Cinatrins A, B, C1, C2 and C3, a family of phospholipase A2 inhibitors were isolated from the fermentation broth of Circinotrichum falcatisporum RF-641. They were found to be novel spiro-gamma-dilactones and gamma-lactones derived from 1,2,3,5-tetra or 1,2,3(or 1,2,4)-trihydroxypentadecane-1,2,3-tricarboxylic acids. Structures were elucidated by MS and NMR studies and chemical transformations. The structure of cinatrin C3 was confirmed by X-ray crystallographic analysis, and its absolute configuration was determined by comparison of the CD spectra with related compounds.