Synthesis and comparative evaluation of two antiviral agents: beta-L-Fd4C and beta-D-Fd4C

The synthesis of beta-D-Fd4C was achieved in a stereoselective fashion from D-xylose. The antiviral activity and cytotoxicity of beta-D-Fd4C was compared with that of beta-L-Fd4C and 3TC (Lamivudine). Of the three agents compared, beta-L-Fd4C was found to be the most potent antiviral agent.     

Linker histone protects linker DNA on only one side of the core particle and in a sequence-dependent manner

The protection against micrococcal nuclease digestion afforded to chromatosomal DNA by the presence of a linker histone (H1(o)) has been quantitatively measured in two reconstituted systems. We have used chromatosomes reconstituted at two distinct positions on a DNA fragment containing the 5S rRNA gene from Lytechinus variegatus and at a specific position on a sequence containing Gal4- and USF-binding sites. In all cases, we find asymmetric protection, with approximately 20 bp protected on one side of the core particle and no protection on the other. We demonstrated through crosslinking experiments that the result is not due to any sliding of the histone core caused by either linker histone addition or micrococcal nuclease cleavage. Because the core particle is itself a symmetric object, the preferred asymmetric location of a linker histone must be dictated by unknown elements in the DNA sequence.     

A new analytic dyad: homosexual analyst, heterosexual patient

The paradoxical thesis is presented that the extraordinary aspect of the analytic experience of a homosexual male analyst and his heterosexual male analysand is that it was ordinary, that the fundamental processes of transference, countertransference, and analysis of defense and resistance were determinative. The unique variations of these processes with this particular patient are explored. The patient entered treatment unaware of the analyst's homosexuality, which he discovered during the analysis. The course of this discovery, its transformations, its defensive uses, its transference meanings, and its fate in the termination are delineated. Through viewing the patient's reactions to the analyst's homosexuality as potential entry points to the transference, the analytic process was enhanced and facilitated.     

Antibiotic sensitization using biphenyl tetrazoles as potent inhibitors of Bacteroides fragilis metallo-beta-lactamase

BACKGROUND: High level resistance to carbapenem antibiotics in gram negative bacteria such as Bacteroides fragilis is caused, in part, by expression of a wide-spectrum metallo-beta-lactamase that hydrolyzes the drug to an inactive form. Co-administration of metallo-beta-lactamase inhibitors to resistant bacteria is expected to restore the antibacterial activity of carbapenems. RESULTS: Biphenyl tetrazoles (BPTs) are a structural class of potent competitive inhibitors of metallo-beta-lactamase identified through screening and predicted using molecular modeling of the enzyme structure. The X-ray crystal structure of the enzyme bound to the BPT L-159,061 shows that the tetrazole moiety of the inhibitor interacts directly with one of the two zinc atoms in the active site, replacing a metal-bound water molecule. Inhibition of metallo-beta-lactamase by BPTs in vitro correlates well with antibiotic sensitization of resistant B. fragilis. CONCLUSIONS: BPT inhibitors can sensitize a resistant B. fragilis clinical isolate expressing metallo-beta-lactamase to the antibiotics imipenem or penicillin G but not to rifampicin.     

Video-assisted endoscopic saphenous vein harvesting for coronary artery bypass grafting

OBJECTIVE: Correlation of immunophenotype with history, anatomical and morphological features of lymphoid neoplasia in the koala. METHODS: Routine necropsies were performed on 51 koalas with suspected lymphoid neoplasia between 1986 and 1997 in New South Wales and Queensland. Immunophenotyping was by an immunoperoxidase method utilising species cross-reactive antibodies raised against human lymphocytes and an antibody raised against koala IgG. Cases were classified according to organs and tissues affected and the morphological features of neoplastic cells. RESULTS: Twenty-six (51%) of the cases were of the T cell immunophenotype, 12 (24%) were of B cell immunophenotype and 13 (25%) did not stain. The age and sex of koalas did not correlate with immunophenotype (P = 0.686 and P = 1.000, respectively). Thirty-two cases were leukaemic and 36 had multiple organ involvement, probably reflecting presentation of koalas at advanced stages of disease. Abdominal tissue involvement was most common (44 cases), followed by nodal (32), atypical (21) and cervicomediastinal (14). The T cell immunophenotype was over-represented among the leukaemic cases (P = 0.013). Generally, the T cell immunophenotype predominated except for many affected atypical tissues. Neoplastic cells were mostly of medium nuclear size with round to oval nuclei. No correlations were found for cell morphology, mitotic index and immunophenotype. CONCLUSION: The prognostic value of an immunophenotypic, anatomical and morphological basis for the classification of lymphoid neoplasia in the koala currently is limited by the need to detect these neoplasms at an early age, the requirement for freshly fixed tissues and the restricted range of available cross-reacting antibodies.