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Biomedical subjects

R G Nelson

Publications and source records attributed to R G Nelson.

119 records · Page 7Linked to original sources
PubMedDate not supplied

Prediabetic blood pressure and familial predisposition to renal disease in Pima Indians with non-insulin-dependent diabetes mellitus.

Renal disease is a frequent complication of non-insulin-dependent diabetes in the Pima Indians from the Gila River Indian Community in Arizona. This review describes the relationship between prediabetic blood pressure and the subsequent development of renal disease, and characterizes the familial aggregation of diabetic renal disease in this population.

Albuminuria↗
PubMedDate not supplied

Sequences homologous to variant antigen mRNA spliced leader in Trypanosomatidae which do not undergo antigenic variation.

Trypanosomes which parasitize mammals have evolved mechanisms to evade immune attack, such as the occupation of 'safe' intracellular sites (for example, Trypanosoma cruzi), or antigenic variation, exemplified by the salivarian trypanosomes (for example, Trypanosoma brucei). Antigenic variation is mediated by sequential expression of single variant surface glycoprotein (VSG) genes, and often involves transposition of the active gene. Every VSG transcript examined shares the same 5' terminal 35-nucleotide leader sequence. In T. brucei, this leader is encoded within a 1.4-kilobase unit tandemly reiterated to form a large array. It is hypothesized that this array is distantly linked to the expressed VSG gene and functions as a multiple promoter of VSG gene transcription, restricting transcription to that gene which, through genomic rearrangement, is placed downstream from the array. Leader and structural gene sequences are presumably juxtaposed by RNA splicing. Here we show that several trypanosomatids, both those which undergo antigenic variation (Trypanosoma congolense and Trypanosoma vivax) and those which do not (T. cruzi and Leptomonas collosoma), contain reiterated sequences homologous to the T. brucei spliced leader (SL). These results suggest that the SL, although utilized in VSG gene expression, is an ancestral sequence also used in the expression of other trypanosomatid genes.

Animals↗
PubMedDate not supplied

Two mechanisms of expression of a predominant variant antigen gene of Trypanosoma brucei.

African trypanosomes evade the host immune response by periodically switching their variant surface glycoprotein (VSG) coat. The resulting, serologically distinct variant antigenic types (VATs) appear in a loosely ordered sequence and those arising early in infections are termed predominant VATs. VAT switching reflects the successive transcriptional activation of single VSG genes from a large repertoire. Activation of some VSG genes is accomplished by duplication of a previously silent basic copy (BC) gene and insertion of this expression linked copy (ELC) near a chromosomal telomere where is is expressed. However, other VSG genes, always located near a telomere, use a non-duplication activation ( NDA ) mechanism. We report here that the gene encoding the predominant IsTat 1.A VSG can be activated with or without duplication. Four of six independently derived clones activated the 1.A gene without gene duplication or detectable rearrangement. The other two contained an active 1.A ELC, possibly generated by a gene conversion extending to the end of the telomere. The ability to utilize both NDA and ELC mechanisms of gene activation and perhaps an alternative mechanism for gene duplication may account for the fact that VAT 1.A is the most predominant VAT of the IsTaR 1 serodeme .

Chromosome Mapping↗
PubMedDate not supplied

Monoclonal antibodies identify a subset of dense granules in Cryptosporidium parvum zoites and gamonts.

Two monoclonal antibodies raised against purified oocysts and excysted sporozoites of Cryptosporidium parvum identified antigens located in the anterior half of sporozoites by indirect immunofluorescence microscopic assay. The monoclonal antibodies also reacted with Triton-X-100-insoluble antigens of asexual and sexual stage parasites developing in epithelial cells in vitro and identified a 110 kilodalton antigen on immunoblots of sodium dodecyl sulfate-extracted oocysts. Immunoblotting reactivity was abolished by prior treatment of blotted antigen with periodic acid suggesting that the monoclonal antibodies recognize a carbohydrate or carbohydrate-dependent epitope(s). By immunoelectron microscopy, the antibodies reacted with a family of small, electron-dense granules located predominantly in the central region of merozoites and also with a population of cytoplasmic inclusions in macrogamonts. In addition, the monoclonal antibodies prominently labeled the parasitophorous vacuole membrane of all intracellular stages examined suggesting that the corresponding antigen(s) may be exocytosed from the granules to become associated with Triton X-100-insoluble components of the vacuolar membrane or cytoskeleton.

Animals↗
PubMedDate not supplied

Characterization of a Cryptosporidium parvum sporozoite glycoprotein.

Polyclonal and monoclonal antibodies directed against Cryptosporidium oocysts or sporozoites were developed to identify and characterize sporozoite pellicle and apical complex antigens. A very large glycoprotein of Cryptosporidium sporozoites was identified by three monoclonal antibodies that also reacted with intracellular merozoites. The glycoprotein was also identified by polyclonal antibodies that were affinity-purified on nitrocellulose-bound recombinant proteins expressed by four lambda gtll genomic clones.

Animals↗
PubMedDate not supplied

Identification and isolation of Cryptosporidium parvum genes encoding microtubule and microfilament proteins.

Microtubules and microfilaments are highly conserved cytoskeletal polymers hypothesized to play essential biomechanical roles in the unusual gliding motility of Apicomplexan zoites and in their invasion of, and development within, host epithelial cells. We have identified and isolated Cryptosporidium parvum genes encoding the microtubule proteins alpha- and beta-tubulin and the microfilament protein actin by screening a lambda gt11 C. parvum genomic DNA library with degenerate oligonucleotide and heterologous cDNA hybridization probes respectively. The alpha- and beta-tubulin genes have been partially sequenced and the deduced peptide sequences show greatest homology with the tubulins of the related parasites, T. gondii and P. falciparum. The complete nucleic acid sequence of the actin gene predicts a 376 amino acid, 42 kDa protein having 85% sequence identity with the P. falciparum actin I and the human gamma-actin proteins. Each of these cytoskeletal protein genes was demonstrated to be of cryptosporidial origin by Southern analyses of C. parvum chromosomes fractionated by pulsed field gel electrophoresis; the cloned alpha- and beta-tubulin genes hybridized with chromosomes of ca. 1,200 and 1,500 kb respectively and the cloned actin gene also hybridized with a 1,200 kb chromosome.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Amplification of a Cryptosporidium parvum gene fragment encoding thymidylate synthase.

Currently, there is no effective therapy for cryptosporidiosis and it is unclear why antifolate drugs which are effective treatments for infections caused by closely related parasites are not also effective against Cryptosporidium parvum. In protozoa, the target of these drugs, dihydrofolate reductase (DHFR), exists as a bifunctional enzyme also manifesting thymidylate synthase (TS) activity and is encoded by a fused DHFR-TS gene. In order to prepare a probe to isolate the C. parvum DHFR-TS gene we have used degenerate oligonucleotides whose sequences are based on strongly conserved regions of TS protein sequence to prime the polymerase chain reaction (PCR) with C. parvum DNA. The PCR amplified a 375-bp DNA fragment which was cloned and sequenced; the deduced amino acid sequence had significant identity with known TS sequences, including strict conservation of all phylogenetically invariant TS amino acid residues. The cloned PCR fragment was used as a probe to isolate a number of overlapping clones from a C. parvum genomic library which were definitively shown to be of cryptosporidial origin by genomic Southern and molecular karyotype analyses. The deduced protein sequence of C. parvum TS was most similar to the bifunctional TS enzymes of Plasmodium chabaudi and Plasmodium falciparum.

Amino Acid Sequence↗