R726L androgen receptor mutation is uncommon in prostate cancer families in the united states

Background A mutation in the androgen receptor ( AR ) gene, namely AR R726L, was described in 2% of Finnish men with sporadic or familial prostate cancer and was associated with an approximately sixfold increased risk of prostate cancer. We set out to determine the incidence of this mutation in a sample of men with either early-onset and/or familial prostate cancer in the United States. Methods Five hundred forty-eight men with prostate cancer from 411 unrelated families participating in the University of Michigan Prostate Cancer Genetics Project (PCGP) were studied. Allele-specific oligonucleotide hybridization was used to detect the presence of the AR R726L mutation in germline DNA. Results None of the 548 prostate cancer patients studied, including 513 White, 29 African American, 3 Asian, and 3 Hispanic men, were found to carry the AR R726L allele. Therefore, the prevalence of this allele is significantly less than that observed among Finnish men with prostate cancer (Fisher's exact test, P  = 0.002). Conclusions The AR R726L allele does not account for a significant proportion of early-onset and/or familial prostate cancer in the United States. Prostate 54: 306–309, 2003. © 2003 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34764/1/10195_ftp.pd

Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury

World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target

Investigation of inter- and intraspecies variation through genome sequencing of Aspergillus section Nigri

Aspergillus section Nigri comprises filamentous fungi relevant to biomedicine, bioenergy, health, and biotechnology. To learn more about what genetically sets these species apart, as well as about potential applications in biotechnology and biomedicine, we sequenced 23 genomes de novo, forming a full genome compendium for the section (26 species), as well as 6 Aspergillus niger isolates. This allowed us to quantify both inter-and intraspecies genomic variation. We further predicted 17,903 carbohydrateactive enzymes and 2,717 secondary metabolite gene clusters, which we condensed into 455 distinct families corresponding to compound classes, 49% of which are only found in single species. We performed metabolomics and genetic engineering to correlate genotypes to phenotypes, as demonstrated for the metabolite aurasperone, and by heterologous transfer of citrate production to Aspergillus nidulans. Experimental and computational analyses showed that both secondary metabolism and regulation are key factors that are significant in the delineation of Aspergillus species.Peer reviewe

Closing gastroschisis: The good, the bad, and the not-so ugly

Purpose: The diagnosis of closing or closed gastroschisis is made when bowel is incarcerated within a closed or nearly closed ring of fascia, usually with associated bowel atresia. It has been described as having a high morbidity and mortality.Methods: A retrospective review of closing gastroschisis cases (n = 53) at six children\u27s hospitals between 2000 and 2016 was completed after IRB approval.Results: A new classification system for this disease was developed to represent the spectrum of the disease: Type A (15%): ischemic bowel that is constricted at the ring but without atresia; Type B (51%): intestinal atresia with a mass of ischemic, but viable, external bowel (owing to constriction at the ring); Type C (26%): closing ring with nonviable external bowel +/- atresia; and Type D (8%): completely closed defect with either a nubbin of exposed tissue or no external bowel. Overall, 87% of infants survived, and long-term data are provided for each type.Conclusions: This new classification system better captures the spectrum of disease and describes the expected long-term results for counseling. Unless the external bowel in a closing gastroschisis is clearly necrotic, it should be reduced and evaluated later. Survival was found to be much better than previously reported.Type of study: Retrospective case series with no comparison group.Level of evidence: Level IV

Prenatal assessment of congenital diaphragmatic hernia at north american fetal therapy network centers: A continued plea for standardization

IntroductionPrenatal work- up for congenital diaphragmatic hernia (CDH) is important for risk stratification, standardization, counseling, and optimal therapeutic choice. To determine current practice patterns regarding prenatal CDH work- up, including prenatal ultrasound and magnetic resonance imaging (MRI) use, and to identify areas for standardization of such evaluation between fetal centers.MethodsA survey regarding prenatal CDH work- up was sent to each member center of the North American Fetal Therapy Network (NAFTNet) (n = 36).ResultsAll responded. Sonographic measurement of lung- to- head ratio (LHR) was determined by all, 89% (32/36) of which routinely calculate observed- to- expected LHR. The method for measuring LHR varied: 58% (21/36) used a - trace- method, 25% (9/36) used - longest axis,- and 17% (6/36) used an - antero- posterior- method. Fetal MRI was routinely used in 78% (28/36) of centers, but there was significant variability in fetal lung volume measurement. Whereas all generated a total fetal lung volume, the planes, methodology and references values varied significantly. All evaluated liver position, 71% (20/28) evaluated stomach position and 54% (15/28) quantified the degree of liver herniation. More consistency in workup was seen between centers offering fetal intervention.ConclusionPrenatal CDH work- up and management differs considerably among North American fetal diagnostic centers, highlighting a need for its standardization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/166359/1/pd5859_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/166359/2/pd5859.pd

Fetal Surgery in the Primate 4.0: A New Technique 30 Years Later

IntroductionOpen fetal surgery requires a hemostatic hysterotomy that minimizes membrane separation. For over 30 years, the standard of care for hysterotomy in the gravid uterus has been the AutoSuture Premium Poly CS*-57 stapler.ObjectiveIn this study, we sought to test the feasibility of hysterotomy in a rhesus monkey model with the Harmonic ACE®+7 Shears.MethodsA gravid rhesus monkey underwent midgestation hysterotomy at approximately 90 days of gestation (2nd trimester; term = 165 ± 10 days) using the Harmonic ACE®+7 Shears. A two-layer uterine closure was completed and the dam was monitored by ultrasound intermittently throughout the pregnancy. At 58 days after hysterotomy (near term), a final surgery was performed to evaluate the uterus and hysterotomy site.ResultsA 3.5-cm hysterotomy was completed in 2 min 7 s. The opening was hemostatic and the membranes were sealed. Immediately after closure and throughout the pregnancy, ultrasound revealed intact membranes without separation and normal amniotic fluid levels. At term, the scar was well healed without signs of thinning or dehiscence.ConclusionsThe Harmonic ACE®+7 Shears produced a hemostatic midgestation hysterotomy with membrane sealing in the rhesus monkey model. Importantly, healing was acceptable