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Biomedical subjects

R L Thompson

Publications and source records attributed to R L Thompson.

At least 91 records · Page 5Linked to original sources
PubMed1988

Movable Finite Automata (MFA) models for biological systems. I: Bacteriophage assembly and operation.

A new class of models, called Movable Finite Automata (MFA) models, is introduced. MFA models are physically realistic, but still share some of the features of cellular automata that make the latter easy to handle mathematically and computationally. They are found to be quite versatile in modeling the self-organization of biological systems. Their use in simulating the interaction of protein molecules in the self-assembly and operation of the T4 bacteriophage is described. The results of these simulations carried out on a microcomputer, are given.

Bacteriophages↗
PubMed1988

Partial rescue of herpes simplex virus neurovirulence with a 3.2 kb cloned DNA fragment.

A herpes simplex virus (HSV) intertypic recombinant (RE6) has been previously shown to be non-neurovirulent following direct intracranial inoculation of mice. An in vitro recombination/in vivo selection strategy was employed to further characterize the gene or genes responsible for the avirulence of this mutant. It was found that RE6 could be converted to a lethal virus by incorporation of wild-type HSV-1 sequences mapping between 0.698 and 0.721 map units. Restriction endonuclease and Southern blot analysis revealed that viral recombinants which incorporated at least part of the cloned 17syn+ sequences were selected by passage in mouse brains in vivo. The recombinants generated with this fragment were at least 50-fold more neuroviurlent than RE6, as determined by the plaque forming unit to lethal dose 50% assay. Further, they displayed a significant increase in ability to replicate in mouse brain tissue following intracranial inoculation. However, these recombinants did not display a replication advantage over RE6 in cultured mouse cells at 38.5 degrees C. Thus, the defect present within this region of the RE6 genome specifically affects replication in the nervous system. In the accompanying paper we analyze the RNA transcription and DNA sequence in this portion of the RE6 and parental strain genomes.

Cloning, Molecular↗
PubMed1988

DNA sequence and RNA transcription through a site of recombination in a non-neurovirulent herpes simplex virus intertypic recombinant.

RE6 is a herpes simplex type-1 (HSV-1) X herpes simplex type-2 (HSV-2) intertypic recombinant that cannot replicate in the adult mouse nervous system. In the accompanying report, we have shown that HSV-1 sequences between 0.698 and 0.721 map units can restore a partial neurovirulent phenotype to RE6. In this report, we have used comparative DNA sequence analysis of RE6, 17syn+ (HSV-1) and HG52 (HSV-2) to demonstrate that this region contains a site of recombination between HSV-1 and HSV-2 sequences in RE6. High resolution transcription analysis has demonstrated that three readily detected transcripts are present in this region of the genome. In addition, the 5' end of a low abundance 5 kb transcript was also located in the right-hand portion of this region. All the transcripts encoded by HSV-1 and HSV-2 in this region of the genome are expressed by the RE6 recombinant. This and our sequence data suggest that the lack of neurovirulence in RE6 is not due to a simple loss in the expression of a transcript or to a defect in a protein encoded by a gene at the site of recombination.

Base Sequence↗
PubMed1987

Periphyton as monitors for heavy metal pollution in the Calcasieu River estuary.

The levels of copper, lead, chromium, zinc, cadmium, arsenic and silver were determined in periphyton specimens obtained with a diatometer collector. Stations selected were along three important bayous of the Calcasieu River system. Distributions of some metals in the organisms were similar to those found in sediment from the same locations, while other metals appeared to be similar to water concentrations. Concentration ratios of periphyton over sediment greatly exceeded one for the metals chromium, zinc, cadmium, arsenic and silver. The concentrations of heavy metals in the periphyton appeared to yield more information about pollutants than either water or sediment samples collected at the periphyton stations.

Journal Article↗
PubMed1987

Cephalosporin, carbapenem, and monobactam antibiotics.

Cephalosporin and related antibiotics are highly effective bactericidal agents of relatively low toxicity. The spectrum of activity varies with the drug but is usually broad. The first-generation cephalosporins, and especially cefazolin, are most active against sensitive staphylococci and streptococci. Most second-generation (except cefoxitin) and third-generation cephalosporins show substantial activity against Haemophilus influenzae. All cephalosporins (except cefsulodin) are active against Klebsiella, Escherichia coli, and Proteus mirabilis, whereas only the third-generation agents have pronounced activity against the other Enterobacteriaceae. Imipenem (a carbapenem) is active against essentially all pathogenic organisms, but aztreonam (a monobactam) is active against only aerobic gram-negative bacilli. Advantages associated with some of the new cephalosporins are once-daily administration and high cerebrospinal fluid levels. With the development of new cephalosporins, however, new toxicities have become apparent, and superinfections and induction of resistance have become greater problems. The cephalosporins are among the most expensive antibiotics in use today; thus, use of these expensive agents must be justified by lower toxicity, greater efficacy, or both in comparison with drugs of more reasonable cost.

Bacteria↗
PubMed1987

Genetic and biological analyses of a herpes simplex virus intertypic recombinant reduced specifically for neurovirulence.

RS6 is a herpes simplex virus intertypic recombinant derived from type 1 strain 17 syn+ and type 2 strain HG52. With a 50% lethal dose of about 10(5) PFU after intracerebral inoculation of mice, RS6 was approximately 100,000 times less neurovirulent than either of its wild-type parental viruses were. When compared with strains 17 syn+ and HG52, RS6 replicated intermediately in primary mouse embryo fibroblasts in vitro at 38.5 degrees C (mouse temperature) and to wild-type peak titers in mouse feet in vivo. In contrast, following intracranial inoculation of mice, RS6 replicated significantly less well than did either of its parental viruses in brains. The genetic defect(s) responsible for the reduced neurovirulence of RS6 was stable after in vitro and in vivo serial passage, was not manifested as temperature-sensitive plaquing in vitro, and did not affect thymidine kinase expression. These data indicate that RS6 has a genetic defect(s) specifically affecting its ability to replicate in the mouse brain. Using marker rescue technologies, we increased the neurovirulence of RS6 and localized one genetic determinant(s) involved with the reduced neurovirulence of this agent to 0.72 to 0.87 map units (and, tentatively, to 0.79 to 0.83 map units) of the herpes simplex virus genome. When coupled with the work suggesting that thymidine kinase expression is essential for efficient replication in nerve tissues and earlier reports from this laboratory and others, the results presented in this study indicate that more than one herpes simplex virus gene is involved with neurovirulence.

Animals↗
PubMed1987

Antibiotic prophylaxis for percutaneous endoscopic gastrostomy. A prospective, randomized, double-blind clinical trial.

Study Objective. To determine if prophylactic use of cefazolin reduces peristomal wound infection associated with percutaneous endoscopic gastrostomy. Design. Prospective, randomized, double-blind, placebo-controlled clinical trial. Setting. Academic medical center, referral-based, gastroenterology service. Patients. One hundred thirty hospitalized patients, 23 of whom were excluded. Of the remaining 107 patients, 52 (group I) were already using antibiotics at the time of randomization for gastrostomy, whereas 55 (group II) were not. Interventions. Patients received either intravenous saline as a placebo or intravenous cefazolin (1 g) 30 minutes before gastrostomy. Measurements and Main Results. For 1 week after gastrostomy, the peristomal area was evaluated and a score assigned each day for erythema (0 to 4), induration (0 to 3), and exudate (0 to 4). A maximum combined score of 8 or more or the development of pus was a criterion for infection. None of the patients in group I developed a wound infection. Only 2 of 27 group II patients given prophylaxis developed a wound infection, compared with 9 of 28 patients not given prophylaxis, a difference of 25% (95% confidence interval, 4.8 to 44.6%; p less than 0.025). The number of patients who developed a wound infection was 0 of 52 in group I and 2 of 27 in group II patients who received cefazolin, a difference of 7.4% (95% confidence interval, -2.5 to 17.3%; p = 0.07). Conclusion. Cefazolin prophylaxis significantly reduces the risk for peristomal wound infection associated with percutaneous endoscopic gastrostomy. It is needed, however, only for patients not already receiving antibiotic treatment at the time of gastrostomy.

Aged↗
PubMed1987

Postmortem findings of the victims of the Jonestown tragedy.

The procedure for processing and identifying the victims of the Jonestown, Guyana tragedy is outlined. Autopsies were performed on seven of the victims, and the autopsy anatomic and toxicologic findings are presented. Problems encountered in the interpretation of the autopsy findings are noted.

Autopsy↗
PubMed1986

A herpes simplex virus mutant is temperature sensitive for reactivation from the latent state: evidence for selective restriction in neuronal cells.

When the replicative defect in the HSV-1 temperature sensitive mutant tsI was repaired, the agent derived (RI-1) was found to possess an additional temperature sensitive lesion limiting its reactivation from the latent state. Thus, when spinal ganglia from latently infected mice were scored for reactivation by cocultivating them with indicator cells in vitro, significantly more were found to be positive at 31 degrees than at 38.5 degrees. To assess a possible relationship between reactivation and replication in neurons, the replication of RI-1 in murine C1300 neuroblastoma cells was studied. In these cells, RI-1 was severely restricted, and viral replication was delayed at 38.5 degrees. Serial passage of RI-1 in neuroblastoma cells at the restrictive temperature resulted in selection of an agent which gained both the capacity to replicate efficiently in neuroblastoma cells and reactivate from the latent state at 38.5 degrees. However, the replication pattern of this neuron adapted virus in mouse embryo fibroblasts remained unchanged from the parental RI-1. Taken together, these results indicate that RI-1 possesses a neuron specific temperature sensitive replicative lesion which is also manifest during reactivation from the latent state.

Animals↗
PubMed1986

Vaccine potential of a live avirulent herpes simplex virus.

We previously described a herpes simplex intertypic recombinant that is completely and specifically non-neurovirulent following intracranial inoculation. In this report the vaccine potential of this mutant (RE6) is analyzed. It is shown that RE6 replicates to wild type levels at the peripheral site of inoculation (the mouse footpad) but, unlike its virulent parental strains, does not replicate to detectable levels in lumbosacral ganglia. A single vaccination with RE6 is sufficient to completely protect mice against subsequent challenge with either HSV-1 or HSV-2. However, this agent establishes latent infections efficiently, and is fully neurovirulent for newborn mice.

Animals↗
PubMed1986

Characterization of the genes encoding herpes simplex virus type 1 and type 2 alkaline exonucleases and overlapping proteins.

A detailed sequence analysis of the herpes simplex virus type 1 (HSV-1) and HSV-2 DNA encoding the alkaline exonuclease mRNA clusters has been completed. Three partially colinear mRNAs (2.3, 1.9, and 0.9 kilobases) are completely encoded within the DNA sequence presented. The putative promoter regions of the transcripts were inserted upstream of a plasmid-borne chloramphenicol acetyl transferase (CAT) gene and assayed for their ability to induce transcription of the CAT gene upon low multiplicity of infection with HSV in transient expression assays. We conclude that the expression of all three transcripts appear to be controlled by individual promoters. The 2.3-kilobase mRNA contains an open translational reading frame sufficient to encode 626 amino acids for the HSV-1 alkaline exonuclease enzyme; this value is 620 amino acids for HSV-2. A comparison of the predicted amino acid sequences of the HSV-1 and HSV-2 alkaline exonuclease enzymes revealed significant amino acid differences in the N-terminal portions of the two proteins; however, computer analyses suggest that the three-dimensional structures of the HSV-1 and HSV-2 nuclease enzymes are very similar. The 0.9-kilobase mRNA contains an open reading frame which shares a small amount of out-of-phase overlap with the C-terminal portion of the alkaline nuclease open reading frame. This open reading frame has the capacity to encode a 96-amino-acid polypeptide (10,500 daltons).

Acetyltransferases↗
PubMed1986

Functional and molecular analyses of the avirulent wild-type herpes simplex virus type 1 strain KOS.

It has been documented that KOS, a laboratory strain of herpes simplex virus type 1, is several orders of magnitude less neurovirulent than most other wild-type strains. Studies initiated to determine the functional nature of the block to neuroinvasiveness and to establish the genes involved have determined that, after footpad inoculation of mice, strain 17 syn+ induced neuropathologic signs (paralysis) at titers of 10(2) and yielded a PFU/50% lethal dose ratio of 10(4). In contrast, KOS was not lethal and did not induce paralysis at inoculation doses of 10(8) PFU. This reduced neurovirulence of KOS could not be explained by the lack of thymidine kinase activity, its inability to replicate in mouse cells maintained in culture at 38.5 degrees C, or its inefficient replication in nonneural tissues in vivo. Kinetic experiments tracing the virus through the nervous system after footpad inoculation showed that KOS was blocked at the level of the spinal ganglia. A cosmid library of strain 17 syn+ was utilized in recombination and in vivo selection experiments with strain KOS to establish the genomic region involved in 17 syn+ neuroinvasiveness. A cosmid clone containing the HindIII A fragment (0.25 to 0.53 map units) of strain 17 syn+ in mixed transfections with full-length KOS DNA yielded recombinants with enhanced neuroinvasiveness.

Animals↗
PubMed1986

Lysis-centrifugation blood culture technique. Clinical impact in Staphylococcus aureus bacteremia.

To determine the clinical impact of enhanced detection of Staphylococcus aureus by a lysis-centrifugation (LC) blood culture system, consecutive cases of S aureus bacteremia during a seven-month period were reviewed. Of 77 clinically significant cases, the LC system detected 70 cases (91%) while a conventional broth system detected 67 cases (87%). Of 60 cases detected by both systems, the LC system was positive earlier than the broth system by one or more days in 34 cases (57%) and later in none. It also detected more (12 vs four of 13) patients with persistent bacteremia who were receiving antimicrobial treatment. Forty-three patients (56%) did not receive appropriate antimicrobial therapy until cultures were reported positive. Enhanced detection of S aureus bacteremia is a clinically important advantage of the LC blood culture technique.

Bacteriological Techniques↗