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Assessing the reproductive health of men with occupational exposures

Asian Journal of Andrology 2014年第1期16卷 23-30页

作者： steven m schrader katherine l marlow Centers for Disease Control and Prevention National Institute for Occupational Safety and Health Division of Applied Research and Technology Cincinnati OH USA.

The earliest report linking environmental （occupational） exposure to adverse human male reproductive effects dates back to1775 when an English physician, Percival Pott, reported a high incidence of scrotal cancer in chimney sweeps. This observation led to safety regulations in the form of bathing requirements for these workers. The fact that male-mediated reproductive harm in humans may be a result of toxicant exposures did not become firmly established until relatively recently, when lancranjan studied lead-exposed workers in Romania in 1975, and later in 1977, when Whorton examined the effects of dibromochloropropane （DBCP） on male workers in California. Since these discoveries, several additional human reproductive toxicants have been identified through the convergence of laboratory and observational findings. many research gaps remain, as the pool of potential human exposures with undetermined effects on male reproduction is vast. This review provides an overview of methods used to study the effects of exposures on male reproduction and their reproductive health, with a primary emphasis on the implementation and interpretation of human studies. Emphasis will be on occupational exposures, although much of the information is also useful in assessing environmental studies, occupational exposures are usually much higher and better defined.

关键词： accessory glands endocrine epidemiology semen sexual function sperm testis toxicology

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High affinity soluble IlT2 receptor:a potent inhibitor of CD8^(+)T cell activation

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Protein & Cell 2010年第12期1卷 1118-1127页

作者： Ruth K.moysey Yi li Samantha J.Paston Emma E.Baston malkit S.Sami Brian J.Cameron Jessie Gavarret Penio Todorov Annelise Vuidepot steven m.Dunn Nicholas J.Pumphrey katherine J.Adams Fang Yuan Rebecca E.Dennis Deborah H.Sutton Andy D.Johnson Joanna E.Brewer Rebecca Ashfield Nikolai m.lissin Bent K.Jakobsen Immunocore limited 57c Milton ParkAbingdonOxonOX144RXUK Current address:Oxford Nanopore Technologies UK Current address:Geneva merck Serono S.A. Switzerland Current address:Adaptimmune limited UK

Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin superfamily receptor IlT2(synonyms:lIR1,mIR7,CD85j),we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex(mHC)class I *** in a dimeric form,either by chemical cross-linking with bivalent polyethylene glycol(PEG)derivatives or as a genetic fusion with human IgG Fc-fragment,the mutants exhibited a further increase in ligand-binding strength due to the avidity effect,with resident half-times(t1/2)on the surface of mHC I-positive cells of many *** novel compounds antagonized the interaction of CD8 co-receptor with mHC I in vitro without affecting the peptide-specific binding of T-cell receptors(TCRs).In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8^(+)cytotoxic T lymphocytes(CTls)in the presence of their target cells,with subnanomolar potency and in a dose-dependent *** a selective inhibitor of CD8^(+)CTl responses,the engineered high affinity IlT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTls and could have potential for the development of novel autoimmunity therapies.

关键词： CD8^(+)T cells cellular activation autoimmunity cell surface molecules binding affinity phage display

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Estimation of PSA Half-life Following Salvage Radiation Therapy

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Journal of Cancer Therapy 2018年第1期9卷 9-15页

作者： Ajay B. Patel katherine S. Tzou michael G. Heckman Colleen S. Thomas Richard J. lee Nitesh Paryani Thomas m. Pisansky Jennifer l. Peterson Robert C. miller Stephen J. Ko laura A. Vallow steven J. Buskirk Northside Radiation Oncology Consultants Atlanta GA USA Department of Radiation Oncology Mayo Clinic Jacksonville FL USA Division of Biostatistics and Informatics Mayo Clinic Jacksonville FL USA Central Florida Cancer Care Center Orlando FL USA TRI Radiation Oncology Kansas City MO USA Department of Radiation Oncology Mayo Clinic Rochester MN USA

Background:?We aim to estimate prostate-specific antigen (PSA) half-life after salvage radiation therapy (SRT) in patients with detectable PSA after radical prostatectomy (RP). methods: A total of 272 patients treated with salvage radiotherapy between July 1987 and July 2010 were included in this IRB approved retrospective analysis. The median pre-salvage radiotherapy dose was 0.6 ng/ml (range, 0.2 - 21.9 ng/ml), 47 patients had at least a minimum tumor stage of T3b, 29 had a Gleason score over 7, and median dose was 66.6 Gy (range, 54.0 - 72.4 Gy). Results: The estimated PSA half-life in our cohort of patients was 3.0 months (95% CI, 2.9 - 3.2 months;range, 0.5 - 28.5 months). There was no evidence of a statistically significant association between PSA half-life and any baseline clinicopathologic characteristics. The median interval between individual PSA measurements was noted to be 4.6 months (range, 0.1 - 20.4 months). The median interval from the start of radiation therapy to the nadir PSA was 6.3 months (range, 1.3 - 79.1 months). PSA half-life remained approximately 3.0 months when accounting for infrequent and outlier PSA values. Conclusion: The PSA half-life after definitive RT has been reported to be approximately 1.6 months. Our analysis found the PSA half-life after SRT to be approximately twice that of patients treated with definitive RT. These results provide useful information to radiation oncologists when counseling patients both before and after SRT regarding expectations about PSA measurements.

关键词： Prostate Salvage PSA PSA Kinetics

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