The utility of PSMA and PSA immunohistochemistry in the cytologic diagnosis of metastatic prostate carcinoma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107502/1/dc23075.pd

Regulation of dopamine receptors in the MtT/W15 transplantable pituitary tumor by estrogen

We investigated the effects of estrogens on the regulation of dopamine receptors in the MtT/W15 transplantable rat pituitary tumor. Diethylstilbestrol (DES) and 17[beta]-estradiol treatment in female rats significantly decreased the number of dopamine binding sites (Bmax) from 85 +/- 3.9 fmol/mg protein in untreated rats to 9.2 +/- 1.2 and 8.2 +/- 2.8 fmol/mg protein in DES and 17[beta]-estradiol-treated rats, respectively, while the binding affinities (Kd) did not change significantly. Testosterone treatment did not change the Bmax, while ovariectomy resulted in a significant increase in the Bmax (146.3 +/- 6.7 fmol/mg protein). The effects of DES on the Bmax were reversible, since removal of the DES for one week before sacrificing the animals led to a marked increase in the Bmax (54.9 +/- 3.1 fmol/mg protein).Pituitaries from normal female rats treated with DES for 6 and 9 weeks had a significant decrease in the Bmax.These results show that the number of dopamine binding sites in the membranes of MtT/W15 tumors is decreased by estrogen treatment and that this effect is reversible after removal of the estrogenic stimulus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26273/1/0000358.pd

The application of immunocytochemistry to direct smears in the diagnosis of effusions

Metastatic malignancy represents a common cause of effusions. Immunocytochemistry (ICC) is useful in confirming malignancy and gaining insight into the site of origin. Cell blocks are commonly utilized for this purpose; nonetheless, when the malignant cells are sparse, they may not be represented in cell blocks thereby precluding immunophenotypic characterization. Thus, we sought to investigate the utility of direct smear preparations as a platform for ICC in the diagnosis of effusions. Air‐dried, unstained direct smears were prepared from 49 malignant effusions and 17 reactive effusions for comparison. ICC for EMA and MOC‐31 highlighted the tumor cells in 91 and 98% of the malignant effusions tested, respectively. EMA immunoreactivity was focally observed within the calretinin‐positive mesothelial cell population in 1 (6%) of the 17 reactive effusions. ICC for MOC‐31 was negative in all reactive effusions. Site‐specific immunomarkers were also evaluated. Immunoreactivity for Napsin‐A and TTF‐1 were observed in 78 and 67% of metastatic lung adenocarcinomas, respectively. ICC for PAX8 highlighted metastatic Müllerian and thyroid carcinomas in 100% of cases tested. CDX‐2 immunoreactivity was observed in 25, 60, and 100% of metastatic gastric, pancreatic, and colorectal adenocarcinomas, respectively. Positivity for p63 was observed in 75% of metastatic urothelial cell carcinomas and the one case of pulmonary squamous cell carcinoma examined. Calretinin ICC highlighted the tumor cells in both malignant mesothelioma cases tested as well as the benign mesothelial cells in the reactive effusions. In conclusion, direct smears represent an effective platform for the performance of ICC in the diagnosis of malignant effusions. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97537/1/22852_ftp.pd

The application of immunocytochemistry to cytologic direct smears of metastatic merkel cell carcinoma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99093/1/dc22807.pd

Application of immunocytochemistry and BRAF mutational analysis to direct smears of metastatic melanoma

BACKGROUND: The cytodiagnosis of melanoma in fine‐needle aspiration (FNA) specimens can be challenging, often requiring the use of immunocytochemistry. As constitutively activating mutations in the BRAF oncogene are present in at least 40% of melanomas, the use of FNA material to interrogate the BRAF mutational status is likely to increase. Because cell blocks, traditionally used for these studies, can occasionally exhibit insufficient tumor cellularity, the authors investigated the utility of direct smears for immunocytochemistry and BRAF mutational analysis. METHODS: Immunocytochemistry for S‐100, HMB‐45, and Mart‐1 was prospectively performed on direct smears in 17 FNAs of metastatic melanoma. Next, BRAF sequencing was performed using DNA isolated from archived Diff‐Quik–stained direct smears for 15 cases. In parallel, sequencing was performed using DNA obtained from corresponding cell blocks. RESULTS: S‐100 positivity in the tumor cells was observed in all 17 cases. HMB‐45 and Mart‐1 positivity was noted in 81% and 88% of cases, respectively. All 3 markers were positive in 76% of cases. Next, of the 15 archived melanoma FNAs tested, BRAF mutations were observed in 8 (53%); 5 and 3 melanomas harbored the V600E and V600K mutation, respectively. Corresponding cell blocks were also tested for all 15 cases, yielding concordant BRAF results in 14 (93%); 1 cell block yielded a false‐negative result. CONCLUSIONS: Cytologic direct smears represent a robust and valuable source of cellular material for immunocytochemistry and molecular studies, especially in instances in which inadequate cell block cellularity is anticipated or encountered. Cancer (Cancer Cytopathol) 2012. © 2011 American Cancer Society. This study demonstrates that direct smears represent a robust and valuable source of cellular material for ancillary studies used in the cytologic diagnosis of melanoma. Direct smears can be effectively used for confirmatory immunocytochemical studies and molecular assays designed to interrogate the BRAF mutational status of melanoma, especially in scenarios in which inadequate cell block cellularity is anticipated or encountered.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90193/1/20180_ftp.pd

Investigation of risk factors for introduction of highly pathogenic avian influenza H5N1 infection among commercial turkey operations in the United States, 2022: a case-control study

Introduction: The 2022–2023 highly pathogenic avian influenza (HPAI) H5N1 outbreak in the United States (U.S.) is the largest and most costly animal health event in U.S. history. Approximately 70% of commercial farms affected during this outbreak have been turkey farms. Methods: We conducted a case-control study to identify potential risk factors for introduction of HPAI virus onto commercial meat turkey operations. Data were collected from 66 case farms and 59 control farms in 12 states. Univariate and multivariable analyses were conducted to compare management and biosecurity factors on case and control farms. Results: Factors associated with increased risk of infection included being in an existing control zone, having both brooders and growers, having toms, seeing wild waterfowl or shorebirds in the closest field, and using rendering for dead bird disposal. Protective factors included having a restroom facility, including portable, available to crews that visit the farm and workers having access and using a shower at least some of the time when entering a specified barn. Discussion: Study results provide a better understanding of risk factors for HPAI infection and can be used to inform prevention and control measures for HPAI on U.S. turkey farms

Investigation of risk factors for introduction of highly pathogenic avian influenza H5N1 virus onto table egg farms in the United States, 2022: a case–control study

Introduction: The 2022–2023 highly pathogenic avian influenza (HPAI) H5N1 outbreak in the United States (U.S.) is the most geographically extensive and costly animal health event in U.S. history. In 2022 alone, over 57 million commercial and backyard poultry in 47 U.S. states were affected. Over 75% of affected poultry were part of the commercial table egg production sector. Methods: We conducted a case–control study to identify potential risk factors for introduction of HPAI virus onto commercial table egg operations. Univariate and multivariable analyses were conducted to compare farm characteristics, management, and biosecurity factors on case and control farms. Results: Factors associated with increased risk of infection included being in an existing control zone, sightings of wild waterfowl, mowing or bush hogging vegetation less than 4 times a month, having an off-site method of daily mortality disposal (off-site composting or burial, rendering, or landfill), and wild bird access to feed/feed ingredients at least some of the time. Protective factors included a high level of vehicle washing for trucks and trailers entering the farm (a composite variable that included having a permanent wash station), having designated personnel assigned to specific barns, having a farm entrance gate, and requiring a change of clothing for workers entering poultry barns. Discussion: Study results improve our understanding of risk factors for HPAI infection and control measures for preventing HPAI on commercial U.S. table egg farms

Investigation of risk factors for introduction of highly pathogenic avian influenza H5N1 infection among commercial turkey operations in the United States, 2022: a case-control study

IntroductionThe 2022–2023 highly pathogenic avian influenza (HPAI) H5N1 outbreak in the United States (U.S.) is the largest and most costly animal health event in U.S. history. Approximately 70% of commercial farms affected during this outbreak have been turkey farms.MethodsWe conducted a case-control study to identify potential risk factors for introduction of HPAI virus onto commercial meat turkey operations. Data were collected from 66 case farms and 59 control farms in 12 states. Univariate and multivariable analyses were conducted to compare management and biosecurity factors on case and control farms.ResultsFactors associated with increased risk of infection included being in an existing control zone, having both brooders and growers, having toms, seeing wild waterfowl or shorebirds in the closest field, and using rendering for dead bird disposal. Protective factors included having a restroom facility, including portable, available to crews that visit the farm and workers having access and using a shower at least some of the time when entering a specified barn.DiscussionStudy results provide a better understanding of risk factors for HPAI infection and can be used to inform prevention and control measures for HPAI on U.S. turkey farms

Applying genetic technologies to combat infectious diseases in aquaculture

Disease and parasitism cause major welfare, environmental and economic concerns for global aquaculture. In this review, we examine the status and potential of technologies that exploit genetic variation in host resistance to tackle this problem. We argue that there is an urgent need to improve understanding of the genetic mechanisms involved, leading to the development of tools that can be applied to boost host resistance and reduce the disease burden. We draw on two pressing global disease problems as case studies—sea lice infestations in salmonids and white spot syndrome in shrimp. We review how the latest genetic technologies can be capitalised upon to determine the mechanisms underlying inter- and intra-species variation in pathogen/ parasite resistance, and how the derived knowledge could be applied to boost disease resistance using selective breeding, gene editing and/or with targeted feed treatments and vaccines. Gene editing brings novel opportunities, but also implementation and dissemination challenges, and necessitates new protocols to integrate the technology into aquaculture breeding programmes. There is also an ongoing need to minimise risks of disease agents evolving to overcome genetic improvements to host resistance, and insights from epidemiological and evolutionary models of pathogen infestation in wild and cultured host populations are explored. Ethical issues around the different approaches for achieving genetic resistance are discussed. Application of genetic technologies and approaches has potential to improve fundamental knowledge of mechanisms affecting genetic resistance and provide effective pathways for implementation that could lead to more resistant aquaculture stocks, transforming global aquaculture.publishedVersio

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead