Papers by John Lake Laurence
Cell, 1991
The par locus of the Enterococcus faecalis plasmid pAD1 is an RNA-regulated addiction module enco... more The par locus of the Enterococcus faecalis plasmid pAD1 is an RNA-regulated addiction module encoding the peptide toxin Fst. Homology searches revealed that Fst belongs to a family of at least nine related peptides encoded on the chromosomes and plasmids of six different Grampositive bacterial species. Comparison of an alignment of these peptides with the results of a saturation mutagenesis analysis indicated regions of the peptides important for biological function. Examination of the genetic context of the fst genes revealed that all of these peptides are encoded within par-like loci with conserved features similar to pAD1 par. All four Ent. faecalis family members were demonstrated to produce the expected toxin-encoding and regulatory RNA products. The locus from the Ent. faecalis plasmid pAMS1 was demonstrated to function as an addiction module and Fst was shown to be toxic to Staphylococcus aureus, suggesting that a plasmid-encoded module in that species is performing the same function. Thus, the pAD1encoded par locus appears to be the prototype of a family of related loci found in several Grampositive species.
Journal of investigative …, 1998
IgA autoantibodies from the sera of some patients with linear IgA bullous dermatosis (LABD) recog... more IgA autoantibodies from the sera of some patients with linear IgA bullous dermatosis (LABD) recognize a 97 kDa antigen (LABD97) located in the lamina lucida of the basement membrane zone. As LABD autoantibodies do not react with the 180 and 230 kDa proteins recognized by bullous pemphigoid autoantibodies, LABD97 has been thought to represent a separate lamina lucida protein. In this study, we purified LABD97 from the extract of human epidermis using a monoclonal antibody immunoaffinity column and analyzed the amino acid sequence of the N terminus of purified LABD97. This revealed a 16 amino acid sequence that was identical to a previously reported sequence of the 180 kDa antigen in bullous pemphigoid (BPAg2). The N terminus was located 41 amino acids downstream from the carboxyl end of the transmembrane domain of BPAg2 and 11 amino acids downstream from the MCW-1 domain, the predominant bullous pemphigoid epitope. Purified LABD97 was subsequently enzymatically digested with endoproteinase Arg C and separated by chromatography, which resulted in multiple peptide fractions. Fourteen of these fractions were subjected to amino acid sequencing. The amino acid sequence of the peptide fractions, totaling 205 amino acids, were identical to sequences contained within the extracellular domain of BPAg2. Whereas the predominant epitope identified with bullous pemphigoid sera is located in the noncollagenous region of this protein, the epitope recognized by LABD sera is either within or adjacent to the collagenous portion. We conclude that LABD97 represents a portion of the extracellular domain of BPAg2 and that the IgA autoantibodies are directed against an epitope within or adjacent to a collagenous domain.
The American journal of …, 1981
Although clinical observations suggest that abrupt discontinuation of propranolol therapy may pre... more Although clinical observations suggest that abrupt discontinuation of propranolol therapy may precipitate myocardial ischemia and infarction in patients with coronary occlusive disease, the physk&qic consequences of propranolol withdrawal are not fully understood. Platelet survival ttmes and heart rate responses to exercise, uprlght tift and isoproterenol were therefore examined In 14 normal subjects before and after abrupt withdrawal of propranolol. Propranolol, 80 to 240 w/day, was given for 24 to 79 days; its effect was confirmed by a lower heart rate during exercise and during infusion of isoproterenol. In 10 subjects, the mean survival time of chromium-Sl-tagged blood platelets decreased from 10.0 days before propranolol to 7.8 days after its withdrawal (p <0.05). One day after withdrawal, the rise in heart rate wfth exercise or titt was sfightly increased from values before propranolol therapy. Two days after withdrawal of propranolol the mean peak heart rate during exercise (185 beats/min) was 12 beats/min higher (p <O.Ol) than the value before propranolob On this same day heart rate Increased more after tilt without medication (i-8 beatdmin, p CO.05) and more after tilt followlng vagal blockade (-I-8 beats/min, p <0.02) than before treatment with propranolol. Seven days afler propranolol withdrawal, heart rate responses to exercise or tilt remained increased. Isoproterenol-induced heart rate responses (5 to 40 ng/kg per min, n = 14), white blood cell beta receptor function (cyclic adenoslne monophosphate production after isqproterenol and 3H-Idihydroalprenolol binding, n = 9) and plasma norepinephrine values at rest and during exercise (n = 7) were each unattered after propran-0101.
The American Journal of …, 1993
Currently available hepatitis B vaccines are recombinant, yeast-derived preparations given in 10-... more Currently available hepatitis B vaccines are recombinant, yeast-derived preparations given in 10-micrograms or 20-micrograms doses. The optimum dose remains controversial. We sought to assess the relative immunogenicity of two hepatitis B vaccines, given in different doses, in older individuals. In a multicenter, double-blind, randomized clinical trial, a total of 460 healthy subjects between 39 and 70 years of age were screened and immunized with either Engerix-B 20 micrograms or Recombivax HB 10 micrograms in standard, intramuscular, 3-dose regimens. Of these, 397 subjects were eligible to continue vaccination. Immunogenicity was measured by determination of antibody to hepatitis B surface antigen (anti-HBs). Seroconversion and seroprotection rates, and geometric mean titers of anti-HBs were calculated at 1, 3, 6, and 8 months after the initial dose of vaccine. Seroprotection rates for subjects receiving the 20-micrograms dose of vaccine were slightly, but not significantly, greater than for subjects receiving the 10-micrograms dose, at each time point. However, at 3 months, males receiving the higher dose had significantly higher seroprotection rates than males receiving the lower dose: 63% versus 37% (p &lt; 0.001). At 8 months, geometric mean titers for the group receiving Engerix-B 20 micrograms were significantly greater than that for the group receiving Recombivax HB 10 micrograms: 840 mIU/mL versus 340 mIU/mL (p = 0.001). Immunization with the 20-micrograms dose of recombinant hepatitis B virus vaccine appeared to result in more rapid development of seroprotective anti-HBs titers in older men and in higher titers of anti-HBs at the completion of vaccination when compared to the 10-micrograms dose. The latter data suggest that the 20-micrograms dose may result in a longer duration of seroprotective anti-HBs titers.
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Papers by John Lake Laurence