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 & Poison control. 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.

Association of Minimal Residual Disease With Clinical Outcome in Pediatric and Adult Acute Lymphoblastic Leukemia: A Meta-analysis.

Abstract: Importance Minimal residual disease (MRD) refers to the presence of disease in cases deemed to be in complete remission by conventional pathologic analysis. Assessing the association of MRD status following induction therapy in patients with acute lymphoblastic leukemia (ALL) with relapse and mortality may improve the efficiency of clinical trials and accelerate drug development. Objective To quantify the relationships between event-free survival (EFS) and overall survival (OS) with MRD status in pediatric and adult ALL using publications of clinical trials and other databases. Data Sources Clinical studies in ALL identified via searches of PubMed, MEDLINE, and clinicaltrials.gov. Study Selection Our search and study screening process adhered to the PRISMA Guidelines. Studies that addressed EFS or OS by MRD status in patients with ALL were included; reviews, abstracts, and studies with fewer than 30 patients or insufficient MRD description were excluded. Data Extraction and Synthesis Study sample size, patient age, follow-up time, timing of MRD assessment (postinduction or consolidation), MRD detection method, phenotype/genotype (B cell, T cell, Philadelphia chromosome), and EFS and OS. Searches of PubMed and MEDLINE identified 566 articles. A parallel search on clinicaltrials.gov found 67 closed trials and 62 open trials as of 2014. Merging results of 2 independent searches and applying exclusions gave 39 publications in 3 arms of patient populations (adult, pediatric, and mixed). We performed separate meta-analyses for each of these 3 subpopulations. Results The 39 publications comprised 13 637 patients: 16 adult studies (2076 patients), 20 pediatric (11 249 patients), and 3 mixed (312 patients). The EFS hazard ratio (HR) for achieving MRD negativity is 0.23 (95% Bayesian credible interval [BCI] 0.18-0.28) for pediatric patients and 0.28 (95% BCI, 0.24-0.33) for adults. The respective HRs in OS are 0.28 (95% BCI, 0.19-0.41) and 0.28 (95% BCI, 0.20-0.39). The effect was similar across all subgroups and covariates. Conclusions and Relevance The value of having achieved MRD negativity is substantial in both pediatric and adult patients with ALL. These results are consistent across therapies, methods of and times of MRD assessment, cutoff levels, and disease subtypes. Minimal residual disease status warrants consideration as an early measure of disease response for evaluating new therapies, improving the efficiency of clinical trials, accelerating drug development, and for regulatory approval. A caveat is that an accelerated approval of a particular new drug using an intermediate end point, such as MRD, would require confirmation using traditional efficacy end points.

Agrobacterium tumefaciens T-complex transport apparatus: a paradigm for a new family of multifunctional transporters in eubacteria.

Abstract: Bacterial conjugation has long served as a model system for developing a mechanistic understanding of how nucleic acids translocate across biological membranes. Early studies of the Escherichia coli F-plasmid conjugation system led to the view that conjugation is a contact-dependent process which, at least among the gram-negative bacteria, requires two cell surface structures in the donor cell that are probably joined. One structure is an extracellular filament termed the sex pilus for initiating the physical coupling of donor and recipient cells. The second is a DNA conductance channel or conjugal pore for transmission of DNA substrates across the donor cell envelope (34, 46). Classically, conjugation systems have been considered to operate on principles that are mechanistically quite different from systems dedicated to protein transport. However, recent studies have identified at least three similarities among conjugation and protein transport processes. First, sequence-based studies have identified homologies among subunits of a variety of eubacterial transport systems, including those dedicated to DNA transfer, selective protein secretion, assembly of type IV fimbriae and flagella, and extrusion of filamentous phage (44). Second, there is an accumulating body of experimental evidence supporting the notion that the conjugal transfer of DNA proceeds via recognition of sequences or motifs associated not with the DNA per se but with proteins bound to the DNA (34 and this minireview). Finally, some members of the type III protein secretion family (see below) recently identified in bacterial pathogens of plants and humans directly “inject” protein substrates into eukaryotic cells by a process requiring cell contact and, in some cases, the elaboration of extracellular filaments; in principle these structures could functionally resemble conjugative sex pili (39, 64). This minireview will focus on recent investigations of the Agrobacterium tumefaciens transport system responsible for delivery of oncogenic DNA (T-complex) across the bacterial envelope. The T-complex transporter belongs to a growing family of transporters whose subunits share extensive sequence similarities. For the present, this secretion family is referred to as a type IV secretion system, as originally proposed by Salmond (72). This classification distinguishes the type IV secretion system from other dedicated secretion pathways, including the type I secretion system exemplified by E. coli hemolysin export, the type II secretion system exemplified by Klebsiella oxytoca pullulanase export, and the type III secretion system exemplified by Yersinia pestis Yop export (for detailed information about these protein export systems, see references 30, 39, 68, and 72). However, as illustrated above, a taxonomic classification based on sequence similarities of transporter subunits is likely to prove obsolete as additional structural or functional similarities are identified among various macromolecular transport systems. By definition, members of the type IV system involved in conjugation transmit DNA to recipient cells by a contact-dependent process. Beyond requiring cell-to-cell contact, however, until very recently almost nothing was known about the biochemical reactions that govern the processing of DNA into a transfer-competent substrate or the transmission of substrate from donor to recipient cells. The first aim of this minireview is to highlight recent work demonstrating sequence and functional similarities between the T-complex transport system and related conjugation and protein export systems. The second aim is to summarize new results from structural studies that define, for the first time, early stages in the assembly of a bacterial conjugation apparatus.

Effects of acculturation and socioeconomic status on obesity and diabetes in mexican americans the san antonio heart study

Abstract: The authors hypothesized that increased socioeconomic status and acculturation of Mexican Americans to mainstream US society would be accompanied by a progressive lessening of obesity and non-insulin-dependent diabetes mellitus. This hypothesis was tested in 1979-1982 in the San Antonio Heart Study, a population-based study of 1,288 Mexican Americans and 929 non-Hispanic whites, aged 25-64 years, randomly selected from three San Antonio neighborhoods: a low-income barrio, a middle-income transitional neighborhood, and a high-income suburb. Socioeconomic status was assessed by the Duncan Socioeconomic Index, a global measure of socioeconomic status based on occupational prestige. Acculturation was assessed by three scales which measure functional integration with mainstream society, value placed on preserving Mexican cultural origin, and attitude toward traditional family structure and sex-role organization. In Mexican-American men, increased acculturation was accompanied by a statistically significant, linear decline in both obesity and diabetes, while socioeconomic status had no significant effect on either outcome. In Mexican-American women, on the other hand, increased acculturation and increased socioeconomic status were accompanied by statistically significant, linear declines in both outcomes. However, the effects of acculturation on obesity and diabetes prevalence in women were stronger than the effects of socioeconomic status. In women, obesity also appeared to be a more important mediator of the relation between socioeconomic status and diabetes than of the relation between acculturation and diabetes. The results of this study suggest that culturally mediated factors exert a more pervasive influence on obesity and diabetes in Mexican Americans than do socioeconomically mediated factors. The influence of socioeconomic status in women, however, cannot be ignored, particularly with regard to obesity.

Neuroimaging, Physical, and Developmental Findings After Inflicted and Noninflicted Traumatic Brain Injury in Young Children

Abstract: Objective To characterize neuroimaging, physical, neurobehavioral, and developmental findings in children with inflicted and noninflicted traumatic brain injury (TBI) and to identify characteristic features of inflicted TBI Methods and Patients Forty children, 0 to 6 years of age, hospitalized for TBI who had no documented history of previous brain injury were enrolled in a prospective longitudinal study TBI was categorized as either inflicted (n = 20) or noninflicted (n = 20) based on the assessment of hospital and county protective services Glasgow Coma Scale scores and neonatal history were comparable in both groups Outcome Measures Acute computed tomography/magnetic resonance imaging studies and physical findings were evaluated Glasgow Outcome Scale scores, cognitive development, and motor functioning were assessed an average of 13 months after TBI χ2 analyses assessed differences in the distribution of findings in the inflicted and noninflicted TBI groups Results Signs of preexisting brain injury, including cerebral atrophy, subdural hygroma, and ex vacuo ventriculomegaly, were present in 45% of children with inflicted TBI and in none of the children with noninflicted TBI Subdural hematomas and seizures occurred significantly more often in children with inflicted TBI Intraparenchymal hemorrhage, edema, skull fractures, and cephalohematomas were similar in both groups Retinal hemorrhage was only identified in the inflicted TBI group Glasgow Outcome Scale scores indicated a significantly less favorable outcome after inflicted than noninflicted TBI Mental deficiency was present in 45% of the inflicted and 5% of the noninflicted TBI groups Conclusions Characteristic features of inflicted TBI included acute computed tomography/magnetic resonance imaging findings of preexisting brain injury, extraaxial hemorrhages, seizures, retinal hemorrhages, and significantly impaired cognitive function without prolonged impairment of consciousness

Reciprocal regulation of haem biosynthesis and the circadian clock in mammals

Abstract: The circadian clock is the central timing system that controls numerous physiological processes. In mammals, one such process is haem biosynthesis, which the clock controls through regulation of the rate-limiting enzyme aminolevulinate synthase 1 (Alas1)1,2. Several members of the core clock mechanism are PAS domain proteins, one of which, neuronal PAS 2 (NPAS2), has a haem-binding motif3,4. Indeed, haem controls activity of the BMAL1–NPAS2 transcription complex in vitro by inhibiting DNA binding in response to carbon monoxide3. Here we show that haem differentially modulates expression of the mammalian Period genes mPer1 and mPer2 in vivo by a mechanism involving NPAS2 and mPER2. Further experiments show that mPER2 positively stimulates activity of the BMAL1–NPAS2 transcription complex and, in turn, NPAS2 transcriptionally regulates Alas1. Vitamin B12 and haem compete for binding to NPAS2 and mPER2, but they have opposite effects on mPer2 and mPer1 expression in vivo. Our data show that the circadian clock and haem biosynthesis are reciprocally regulated and suggest that porphyrin-containing molecules are potential targets for therapy of circadian disorders.