Biomedical subjects

D Lehman

Publications and source records attributed to D Lehman.

31 records · Page 2Linked to original sources

PubMed1991

Expression and characterization of the N-terminal half of antistasin, an anticoagulant protein derived from the leech Haementeria officinalis.

Antistasin, a 15-kDa anticoagulant protein isolated from the salivary glands of the Mexican leech Haementeria officinalis, has been shown to be a potent inhibitor of factor Xa in the blood coagulation cascade. Antistasin possesses a twofold internal homology between the N- and C-terminal halves of the molecule, suggesting a gene duplication event in the evolution of the antistasin gene. This structural feature also suggests that either or both halves of the protein may possess biological activity if expressed as separate domains. Because the N-terminal domain contains a factor Xa P1-reactive site, we chose to express this domain in an insect cell baculovirus expression system. Characterization of this recombinant half antistasin molecule reveals that the N-terminal domain inhibits factor Xa in vitro, with a K(i) of 1.7 nM.

Amino Acid Sequence↗

PubMed1989

Vero cell-expressed Epstein-Barr virus (EBV) gp350/220 protects marmosets from EBV challenge.

The Epstein-Barr virus (EBV) major membrane antigen, gp350/220, was purified from expressing, genetically engineered Vero cells. The antigen, formulated either with alum or Freund's adjuvant, was inoculated into EBV infection-susceptible marmosets. After several injections, most of the marmosets developed anti-gp350/220 antibodies, and several exhibited virus-neutralizing activity. The immune response elicited by the alum-absorbed antigen proved to be protective upon virus challenge of the inoculated animals. Protection did not correlate with the presence of neutralizing antibodies.

Animals↗

PubMed1988

Antigenic analysis of the Epstein-Barr virus major membrane antigen (gp350/220) expressed in yeast and mammalian cells: implications for the development of a subunit vaccine.

The Epstein-Barr virus (EBV) major surface membrane antigen, gp350/220, was expressed in recombinant yeast cells and in several recombinant mammalian cell lines. Each of the expressed proteins was analyzed for its ability to bind to a panel of anti-gp350/220 monoclonal antibodies and to a series of anti-EBV positive human sera. The antigens also were used as immunogens for the immunization of rabbits. Each expressed protein was found to be unique both in its pattern of reactivity to the various antibodies and in the spectrum of antibody induced following animal immunization. These results suggest that cell-specific post-translational modifications critically influence the antigenic presentation of the expressed proteins. Nonetheless, all of the mammalian cell-derived versions of the membrane antigen were found capable of inducing EBV-specific neutralizing antibodies.

Animals↗

PubMed1987

Site-specific cleavage of a fusion protein by renin.

A double-stranded synthetic oligonucleotide that codes for an amino acid sequence specifically recognized and cleaved by the endopeptidase, renin, was inserted into a plasmid expression vector. The double-stranded oligonucleotide was placed at the junction between the sequences coding for two distinct domains of a fusion protein. The vector used for this analysis expressed a 190-kD Epstein-Barr virus membrane antigen (EBV-MA)-beta-galactosidase (beta-gal) fusion protein (Beisel et al., 1985). The resultant novel protein product expressed by the new construction can be cleaved specifically by renin to yield two distinct polypeptides, EBV-MA and beta-gal, corresponding to the two domains of the original fusion protein product.

Antigens, Viral↗

PubMed1985

Genetic evidence for role of extracellular proteinase in virulence of Candida albicans.

The relationship between extracellular proteinase and the virulence for mice in Candida albicans was studied by using a set of three isolates. The set included a proteinase-producing parent (C9), a proteinase-deficient mutant derived from C9 by nitrous acid treatment (C9M1), and a spontaneous revertant (C9M1M) obtained by mouse passage of C9M1. The morphological markers and the carbon assimilation pattern were identical in these isolates. Isolate C9 produced a high level of proteinase in vitro and caused fatal infection (100%) within 21 days. The mutant produced no detectable enzymes in vitro, and all mice survived until day 22. Only 30% of the mice infected with C9M1 died between day 23 and 30. The isolates recovered from the dead mice were found to be proteinase sufficient, indicating that the mice died after the organism in tissue had reverted. The C9M1M isolate produced proteinase in vitro at 44% the level of C9 and induced fatal infection in 90% of the mice within 30 days. The number of CFU recovered from the kidneys correlated with the level of proteinase produced in vitro and, in turn, the rate of fatal infection produced by the isolates. These results support a previous observation indicating that proteinase activity is one of the virulence factors associated with C. albicans.

Animals↗

PubMed1978

Multiple adjuvant therapy on a murine fibrosarcoma: actinomycin-D, X-irradiation and local tumor hyperthermia.

The tumoricidal activities of single dose x-irradiation (RAD) and concomitant Actinomycin D (AMD) with or without local tumor hyperthermia (LTH) on an in vivo Methylcholanthreme-induced fibrosarcoma (Meth-A) are described. The addition of LTH enhanced the actions of AMD, RAD and AMD + RAD; the trimodality treatment was most effective. Based on delay of tumor growth, the radiation dose reduction factors for AMD + RAD + LTH compared to RAD; AMD + RAD + LTH, were approximately 2.8, 2.1, and 1.8, respectively. The shape of the curves suggests a further decrease in the ability of the tumor cell to repair sublethal damage with AMD + RAD + LTH. The clinical relevance is not determined.

Animals↗

PubMed1977

Average multichannel EEG potential fields evoked from upper and lower hemi-retina: latency differences.

Checkerboard reversals shown to the upper hemiretina evoke EEG potentials which in anterior-posterior derivations are approximately inverted in polarity compared with potentials evoked by lower hemiretinal stimulation. Using a 48-channel system, EEG scalp field distributions of such responses were mapped. Examination of the map sequences shows that occipital positive maximal field values start to develop at about the same time in the two stimulus conditions, but peak much earlier and somewhat more anteriorly for upper than for lower hemiretinal stimulation. Thus, there is a difference of response latency in the two conditions, which accounts for the approximate inversion of polarity. Possible correlations with reports of higher receptor cell density, higher visual acuity, and shorter motor reaction time of the upper hemiretinal system are noted.

Adult↗

PubMed1974