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Biomedical subjects

D S Peterson

Publications and source records attributed to D S Peterson.

17 recordsLinked to original sources

Nicotine enhances interleukin production of rat splenic T lymphocytes.

Very little is known regarding the effects of nicotine, the most pharmacologically active component of tobacco products, on T lymphocyte activity or interleukin production. Therefore, rats were implanted subcutaneously with osmotic mini-pumps containing either physiological saline, nicotine (1.5 mg/kg/day) or a high dose of nicotine (4.5 mg/kg/day) for a period of 14 days. The ability of the splenic T lymphocytes to respond to the polyclonal T lymphocyte mitogens, Concanavalin A (ConA) or phytohemagglutinin (PHA), and the ability of mitogen stimulated splenic T lymphocytes to produce interleukin 2 (IL2) were determined. Treatment with nicotine suppressed, in a dose dependent fashion, the ability of splenic T lymphocytes to respond to mitogen, but dramatically enhanced the ability of mitogen stimulated lymphocytes to generate IL2.

Animals

Nucleotide sequence and transcription of a trypomastigote surface antigen gene of Trypanosoma cruzi.

In previous studies we identified a 500-bp segment of the gene, TSA-1, which encodes an 85-kDa trypomastigote-specific surface antigen of the Peru strain of Trypanosoma cruzi. TSA-1 was shown to be located at a telomeric site and to contain a 27-bp tandem repeat unit within the coding region. This repeat unit defines a discrete subset of a multigene family and places the TSA-1 gene within this subset. In this study, we present the complete nucleotide sequence of the TSA-1 gene from the Peru strain. By homology matrix analysis, fragments of two other trypomastigote specific surface antigen genes, pTt34 and SA85-1.1, are shown to have extensive sequence homology with TSA-1 indicating that these genes are members of the same gene family as TSA-1. The TSA-1 subfamily was also found to be active in two other strains of T. cruzi, one of which contains multiple telomeric members and one of which contains a single non-telomeric member, suggesting that transcription is not necessarily dependent on the gene being located at a telomeric site. Also, while some of the sequences found in this gene family are present in 2 size classes of poly(A)+ RNA, others appear to be restricted to only 1 of the 2 RNA classes.

Amino Acid Sequence

Prevalence of the dihydrofolate reductase Asn-108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the Brazilian Amazon.

Pyrimethamine resistance in cultivated laboratory isolates of Plasmodium falciparum is linked to the dihydrofolate reductase mutation Asn-108, a mutation that acts by interrupting drug binding within the active site of the enzyme. To determine the prevalence of this mutation in endemic regions harboring pyrimethamine-resistant malaria, we used a mutation-specific polymerase chain reaction assay to survey P. falciparum strains from a wide section of the Brazilian Amazon. Mutations were identified directly from blood samples without intervening steps of in vitro cultivation. Of 42 samples collected from four states in Brazil, 38 (90%) contained the Asn-108 codon AAC that confers pyrimethamine resistance, four samples contained only the wild-type Ser-108 codon AGC, and none contained the Thr-108 codon ACC found in cycloguanil-resistant pyrimethamine-sensitive strains. These findings indicate that a very high incidence of the Asn-108 DHFR mutation is responsible for pyrimethamine resistance in the Amazon, and they are consistent with recent failure rates reported for Fansidar (pyrimethamine-sulfadoxine). We suggest that limited use of proguanil be evaluated as an alternative to pyrimethamine.

Animals

Molecular basis of differential resistance to cycloguanil and pyrimethamine in Plasmodium falciparum malaria.

Proguanil and pyrimethamine are antifolate drugs with distinct chemical structures that are used commonly in the prophylaxis and treatment of Plasmodium falciparum malaria. Clinical reports and field studies have suggested that some parasites refractory to proguanil can be treated with pyrimethamine, and vice versa. Analysis of the P. falciparum dihydrofolate reductase (DHFR) from different parasites reveals the structural basis for differential susceptibility to these antifolate drugs. Parasites harboring a pair of point mutations from Ala-16 to Val-16 and from Ser-108 to Thr-108 are resistant to cycloguanil (the active metabolite of proguanil) but not to pyrimethamine. A single Asn-108 mutation, on the other hand, confers resistance to pyrimethamine with only a moderate decrease in susceptibility to cycloguanil. Significant cross-resistance to both drugs occurs in parasites having mutations that include Ser-108----Asn-108 and Ile-164----Leu-164. These results reflect the distinct structures of pyrimethamine and cycloguanil and suggest fine differences in binding within the active site cavity of DHFR. Alternative inhibitors, used alone or in combination, may be effective against some strains of cycloguanil- or pyrimethamine-resistant malaria.

Amino Acid Sequence

The 85-kd surface antigen gene of Trypanosoma cruzi is telomeric and a member of a multigene family.

In previous studies we identified a 500 bp DNA fragment from the genome of Trypanosoma cruzi which encoded epitopes present in an 85 kd trypomastigote-specific surface antigen. A unique feature of this DNA insert was the presence of a 27 bp tandem repeat unit within the putative coding region. The findings presented here show that the gene which encodes this particular surface protein is a member of a multigene family, and that the 27 bp repeat unit defines a subset of this family. Only four separate members of the family contain sequences homologous to the 27 bp repeat unit. Of these, three have been cloned and shown by direct nucleotide sequence analysis not to contain the original 500 bp fragment. By restriction enzyme analysis, the 500 bp fragment is inferred to be present in a 5.4 kb EcoRI genomic DNA fragment that is refractory to isolation by standard cloning procedures. Preferential sensitivity of this fragment to digestion with Bal31 nuclease indicates that it is likely to be telomeric, thus explaining the inability to obtain it in several different recombinant DNA libraries. In order to determine which of the four members were transcribed, 26 cDNA recombinants having sequence homology with the 27 bp repeat were examined. Restriction enzyme maps and nucleotide sequence analysis of these cDNAs indicate that transcription occurs almost exclusively from the telomeric member of the family.

Animals

Dental management for children with chronic renal failure undergoing hemodialysis therapy.

Patients with chronic renal failure who are undergoing hemodialysis therapy demonstrate problems of significant importance for dental treatment. A case is presented in which secondard hyperparathyroidism, resulting from renal failure and hemodialysis, was noted in a child. Other relationships between renal failure, hemodialysis, and dental care were also presented.

Child

Cloning of a major surface-antigen gene of Trypanosoma cruzi and identification of a nonapeptide repeat.

The parasitic protozoan Trypanosoma cruzi can establish infection in humans and other vertebrate hosts through direct penetration of host cells by trypomastigotes transmitted by the insect vector. Although the molecular processes involved in trypomastigote interiorization of vertebrate cells are unknown, several studies suggest that surface glycoproteins are involved. It is likely that the proteins involved are specific to the trypomastigote stage of the parasite, since only trypomastigotes found in both the insect vector and the vertebrate host bloodstream are capable of invading vertebrate cells. In contrast, the epimastigote stage, found exclusively in the vector, and the amastigote stage, an intracellular stage in the vertebrate host, cannot penetrate the cell directly. We have therefore concentrated our efforts on trypomastigote surface proteins and, along with others, have identified two trypomastigote-specific surface glycoproteins of relative molecular mass (Mr) 90,000 (90K) and 85,000 (85K). Antibody neutralization experiments indicate that the 85K glycoprotein is necessary for efficient interiorization of trypomastigotes in mammalian cells. Here we describe the molecular cloning of a genomic DNA fragment that encodes antigenic determinants present in the 85K trypomastigote surface antigen. The polypeptide fragment encoded by the cloned DNA is recognized by serum from a T. cruzi-infected host and is inferred by DNA sequence analysis to contain a nonapeptide unit that is tandemly repeated five times. Also, the messenger complementary to the cloned DNA fragment is present only in the trypomastigote stage of the parasite.

Antigens, Protozoan

Pain sensation related to local anesthesia injected at varying temperatures.

The purpose of the study was to determine whether local anesthetic solution warmed to body temperature (37° C) produced less pain on injection than an anesthetic solution injected at room temperature (21° C) and to determine which solution resulted in quicker anesthetic onset. It was found that the subjects experienced no difference in pain during injection of warm and cold anesthetic solution given respectively in the maxillary buccal sulcus area. The time of anesthetic onset was also not influenced by solution temperature.

Adult