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T Speed

Publications and source records attributed to T Speed.

8 recordsLinked to original sources
PubMed2006

Mitochondrial-related gene expression changes are sensitive to agonal-pH state: implications for brain disorders.

Mitochondrial defects in gene expression have been implicated in the pathophysiology of bipolar disorder and schizophrenia. We have now contrasted control brains with low pH versus high pH and showed that 28% of genes in mitochondrial-related pathways meet criteria for differential expression. A majority of genes in the mitochondrial, chaperone and proteasome pathways of nuclear DNA-encoded gene expression were decreased with decreased brain pH, whereas a majority of genes in the apoptotic and reactive oxygen stress pathways showed an increased gene expression with a decreased brain pH. There was a significant increase in mitochondrial DNA copy number and mitochondrial DNA gene expression with increased agonal duration. To minimize effects of agonal-pH state on mood disorder comparisons, two classic approaches were used, removing all subjects with low pH and agonal factors from analysis, or grouping low and high pH as a separate variable. Three groups of potential candidate genes emerged that may be mood disorder related: (a) genes that showed no sensitivity to pH but were differentially expressed in bipolar disorder or major depressive disorder; (b) genes that were altered by agonal-pH in one direction but altered in mood disorder in the opposite direction to agonal-pH and (c) genes with agonal-pH sensitivity that displayed the same direction of changes in mood disorder. Genes from these categories such as NR4A1 and HSPA2 were confirmed with Q-PCR. The interpretation of postmortem brain studies involving broad mitochondrial gene expression and related pathway alterations must be monitored against the strong effect of agonal-pH state. Genes with the least sensitivity to agonal-pH could present a starting point for candidate gene search in neuropsychiatric disorders.

Antidepressive Agents↗
PubMed2001

Identification of proteins from Plasmodium falciparum that are homologous to reticulocyte binding proteins in Plasmodium vivax.

Plasmodium falciparum infections can be fatal, while P. vivax infections usually are not. A possible factor involved in the greater virulence of P. falciparum is that this parasite grows in red blood cells (RBCs) of all maturities whereas P. vivax is restricted to growth in reticulocytes, which represent only approximately 1% of total RBCs in the periphery. Two proteins, expressed at the apical end of the invasive merozoite stage from P. vivax, have been implicated in the targeting of reticulocytes for invasion by this parasite. A search of the P. falciparum genome databases has identified genes that are homologous to the P. vivax rbp-1 and -2 genes. Two of these genes are virtually identical over a large region of the 5' end but are highly divergent at the 3' end. They encode high-molecular-mass proteins of >300 kDa that are expressed in late schizonts and localized to the apical end of the merozoite. To test a potential role in merozoite invasion of RBCs, we analyzed the ability of these proteins to bind to mature RBCs and reticulocytes. No binding to mature RBCs or cell preparations enriched for reticulocytes was detected. We identified a parasite clone that lacks the gene for one of these proteins, showing that the gene is not required for normal in vitro growth. Antibodies to these proteins can inhibit merozoite invasion of RBCs.

Amino Acid Sequence↗
PubMed1996

Estimation of antigen-responsive T cell frequencies in PBMC from human subjects.

A new method for estimating the frequency of antigen-responsive T cells, using a cell proliferation assay, is described. In this assay, the uptake of tritiated thymidine by peripheral blood mononuclear cells which have been exposed to antigen, is measured for each well on a microtiter plate. Whereas this assay is generally used as part of a limiting dilution assay, here we estimate the frequency of responding cells using a single, carefully chosen cell density. The traditional analysis of such data uses a cut-off to separate wells which contain no responding cells and wells which contain at least one responding cell. The new method uses the scintillation count to estimate the number of responding cells for each well on the plate. We do this by fitting a two-stage model, the first stage being a Poisson model with antigen-specific frequency parameters, and the second stage a linear model with plate-specific parameters.

Cells, Cultured↗
PubMed1986

Comparison of nitroprusside, nitroglycerin, and deep isoflurane anesthesia for induced hypotension.

Three methods of inducing hypotension were studied for their effects on the cardiovascular system and intrapulmonary shunting. Thirty patients were anesthetized with isoflurane in 70% N2O to a total of 1.25 to 1.3 MAC. Patients were divided into three groups of 10 each on the basis of the drug used to induce hypotension; sodium nitroprusside (SNP), nitroglycerin (NTG), or deep isoflurane anesthesia (ISF). Cardiac index was significantly decreased by NTG and ISF at a mean arterial blood pressure of 40 mm Hg compared to SNP (P less than 0.05). Systemic vascular resistance was decreased in all groups. Mixed venous oxygen content was significantly decreased from control in the NTG and ISF groups. There was no difference between the groups in arterial and mixed venous O2 content. Intrapulmonary shunting decreased with induction and, in the NTG and SNP groups, increased slightly but not significantly with induction of hypotension. Our data do not show a clear superiority of any agent over the other to induce hypotension, although SNP and perhaps ISF appear to be better than NTG to induce hypotension.

Blood Pressure↗