University of Texas Health Science Center at Houston

About: University of Texas Health Science Center at Houston is a education organization based out in Houston, Texas, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 27309 authors who have published 42520 publications receiving 2151596 citations. The organization is also known as: UTHealth & The UT Health Science Center at Houston.

Incidence and risk factors in sudden unexpected death in epilepsy: A prospective cohort study

Abstract: Objective: To determine incidence of and risk factors for sudden unexpected death in epilepsy (SUDEP). Methods: Three epilepsy centers enrolled 4,578 patients and prospectively followed these patients for 16,463 patient-years. The cohort was screened for death annually. Deaths were investigated to determine whether SUDEP occurred. Potential risk factors were compared in SUDEP cases and in controls enrolled contemporaneously at the same center. Results: Incidence of SUDEP was 1.21/1,000 patient-years and was higher among women (1.45/1,000) than men (0.98/1,000). SUDEP accounted for 18% of all deaths. Occurrence of tonic-clonic seizures, treatment with more than two anticonvulsant medications, and full-scale IQ less than 70 were independent risk factors for SUDEP. The number of tonic-clonic seizures was a risk factor only in women. The presence of cerebral structural lesions and use of psychotropic drugs at the last visit were not risk factors for SUDEP in this cohort. Subtherapeutic anticonvulsant levels at the last visit were equally common in the two groups. No particular anticonvulsant appeared to be associated with SUDEP. Conclusions: These results support the idea that tonic-clonic seizures are an important proximate cause of SUDEP. This information creates a risk profile for SUDEP that may help direct preventative efforts.

CTLA-4 blockade increases IFNγ-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients

Abstract: Significant anti-tumor responses have been reported in a small subset of cancer patients treated with the immunotherapeutic agent anti-CTLA-4 antibody. All clinical trials to date, comprising over 3,000 patients, have been conducted in the metastatic disease setting, which allows for correlation of drug administration with clinical outcome but has limited analyses of intermediate biomarkers to indicate whether the drug has impacted human immune responses within the tumor microenvironment. We conducted a pre-surgical clinical trial in six patients with localized bladder cancer, which allowed for correlation of drug administration with biomarkers in both blood and tumor tissues but did not permit correlation with clinical outcome. We found that CD4 T cells from peripheral blood and tumor tissues of all treated patients had markedly increased expression of inducible costimulator (ICOS). These CD4+ICOShi T cells produced IFN-gamma (IFNγ) and could recognize the tumor antigen NY-ESO-1. Increase in CD4+ICOShi cells led to an increase in the ratio of effector to regulatory T cells. To our knowledge, these are the first immunologic changes reported in both tumor tissues and peripheral blood as a result of treatment with anti-CTLA-4 antibody, and they may be used to guide dosing and scheduling of this agent to improve clinical responses.

Pseudogenes as a paradigm of neutral evolution

Abstract: On the neutral mutation hypothesis1–3, the rate of nucleotide substitution is expected to be higher for functionally less important genes or parts of genes than for functionally more important genes, as the latter would be subject to stronger purifying (negative) selection2–4. On the other hand, selectionists believe that most nucleotide substitutions are caused by positive darwinian selection5,6, in which case the rate of nucleotide substitution in functionally unimportant genes or parts of genes2,7 is expected to be relatively lower because the mutations in these regions of DNA would not produce any significant selective advantages. Kimura8 and Jukes9 have argued that the higher substitution rate observed at the third positions of codons than at the first two positions supports the neutral mutation hypothesis, as most third-position substitutions are synonymous and do not change the amino acids encoded, although others5,10 have discussed the possibility that third-position substitutions are subject to positive darwinian selection. Recently, Kimura11 noted that the mouse globin pseudogene, ψα3, evolved faster than the normal mouse α1 gene, although he did not compute the substitution rate. Here, we present a method of computing the rate of nucleotide substitution for pseudogenes, and report that the three recently discovered pseudogenes show an extremely high rate of nucleotide substitution. As these pseudogenes apparently have no function, this finding strongly supports the neutral mutation hypothesis.