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31 results on '"Mendel, Matthew"'

3. Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington’s disease

Author

Zeitler, Bryan, Froelich, Steven, Marlen, Kimberly, Shivak, David A, Yu, Qi, Li, Davis, Pearl, Jocelynn R, Miller, Jeffrey C, Zhang, Lei, Paschon, David E, Hinkley, Sarah J, Ankoudinova, Irina, Lam, Stephen, Guschin, Dmitry, Kopan, Lexi, Cherone, Jennifer M, Nguyen, Hoang-Oanh B, Qiao, Guijuan, Ataei, Yasaman, Mendel, Matthew C, Amora, Rainier, Surosky, Richard, Laganiere, Josee, Vu, B Joseph, Narayanan, Anand, Sedaghat, Yalda, Tillack, Karsten, Thiede, Christina, Gärtner, Annette, Kwak, Seung, Bard, Jonathan, Mrzljak, Ladislav, Park, Larry, Heikkinen, Taneli, Lehtimäki, Kimmo K, Svedberg, Marie M, Häggkvist, Jenny, Tari, Lenke, Tóth, Miklós, Varrone, Andrea, Halldin, Christer, Kudwa, Andrea E, Ramboz, Sylvie, Day, Michelle, Kondapalli, Jyothisri, Surmeier, D James, Urnov, Fyodor D, Gregory, Philip D, Rebar, Edward J, Muñoz-Sanjuán, Ignacio, and Zhang, H Steve

Published
2019
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4. Resolution of hepatic fibrosis after ZFN-mediated gene editing in the PiZ mouse model of human α1-antitrypsin deficiency

Author

Li, Yanfeng, primary, Guha, Chandan, additional, Asp, Patrik, additional, Wang, Xia, additional, Tchaikovskya, Tatyana L., additional, Kim, Kenneth, additional, Mendel, Matthew, additional, Cost, Gregory J., additional, Perlmutter, David H., additional, Roy-Chowdhury, Namita, additional, Fox, Ira J., additional, Conway, Anthony, additional, and Roy-Chowdhury, Jayanta, additional

Published
2023
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5. Clinical Scale Zinc Finger Nuclease-mediated Gene Editing of PD-1 in Tumor Infiltrating Lymphocytes for the Treatment of Metastatic Melanoma

Author

Beane, Joal D, Lee, Gary, Zheng, Zhili, Mendel, Matthew, Abate-Daga, Daniel, Bharathan, Mini, Black, Mary, Gandhi, Nimisha, Yu, Zhiya, Chandran, Smita, Giedlin, Martin, Ando, Dale, Miller, Jeff, Paschon, David, Guschin, Dmitry, Rebar, Edward J, Reik, Andreas, Holmes, Michael C, Gregory, Philip D, Restifo, Nicholas P, Rosenberg, Steven A, Morgan, Richard A, and Feldman, Steven A

Published
2015
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6. Correction of the sickle cell disease mutation in human hematopoietic stem/progenitor cells

Author

Hoban, Megan D., Cost, Gregory J., Mendel, Matthew C., Romero, Zulema, Kaufman, Michael L., Joglekar, Alok V., Ho, Michelle, Lumaquin, Dianne, Gray, David, Lill, Georgia R., Cooper, Aaron R., Urbinati, Fabrizia, Senadheera, Shantha, Zhu, Allen, Liu, Pei-Qi, Paschon, David E., Zhang, Lei, Rebar, Edward J., Wilber, Andrew, Wang, Xiaoyan, Gregory, Philip D., Holmes, Michael C., Reik, Andreas, Hollis, Roger P., and Kohn, Donald B.

Published
2015
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7. Off-the-shelf, steroid-resistant, IL13Rα2-specific CAR T cells for treatment of glioblastoma

Author

Brown, Christine E, Rodriguez, Analiz, Palmer, Joycelynne, Ostberg, Julie R, Naranjo, Araceli, Wagner, Jamie R, Aguilar, Brenda, Starr, Renate, Weng, Lihong, Synold, Timothy W, Tran, Vivi, Wang, Shelley, Reik, Andreas, D’Apuzzo, Massimo, Ressler, Julie A, Zhou, Yuanyue, Mendel, Matthew, Gregory, Philip D, Holmes, Michael C, Tang, Winson W, Forman, Stephen J, Jensen, Michael C, and Badie, Behnam

Subjects
Cancer Research, Oncology, T-Lymphocytes, Clinical Investigations, Interleukin-13 Receptor alpha2 Subunit, Humans, Steroids, Neurology (clinical), Glioblastoma, Glucocorticoids, Immunotherapy, Adoptive, Xenograft Model Antitumor Assays, Dexamethasone
Abstract

Background Wide-spread application of chimeric antigen receptor (CAR) T cell therapy for cancer is limited by the current use of autologous CAR T cells necessitating the manufacture of individualized therapeutic products for each patient. To address this challenge, we have generated an off-the-shelf, allogeneic CAR T cell product for the treatment of glioblastoma (GBM), and present here the feasibility, safety, and therapeutic potential of this approach. Methods We generated for clinical use a healthy-donor derived IL13Rα2-targeted CAR+ (IL13-zetakine+) cytolytic T-lymphocyte (CTL) product genetically engineered using zinc finger nucleases (ZFNs) to permanently disrupt the glucocorticoid receptor (GR) (GRm13Z40-2) and endow resistance to glucocorticoid treatment. In a phase I safety and feasibility trial we evaluated these allogeneic GRm13Z40-2 T cells in combination with intracranial administration of recombinant human IL-2 (rhIL-2; aldesleukin) in six patients with unresectable recurrent GBM that were maintained on systemic dexamethasone (4-12 mg/day). Results The GRm13Z40-2 product displayed dexamethasone-resistant effector activity without evidence for in vitro alloreactivity. Intracranial administration of GRm13Z40-2 in four doses of 108 cells over a two-week period with aldesleukin (9 infusions ranging from 2500–5000 IU) was well tolerated, with indications of transient tumor reduction and/or tumor necrosis at the site of T cell infusion in four of the six treated research subjects. Antibody reactivity against GRm13Z40-2 cells was detected in the serum of only one of the four tested subjects. Conclusions This first-in-human experience establishes a foundation for future adoptive therapy studies using off-the-shelf, zinc-finger modified, and/or glucocorticoid resistant CAR T cells.

Published
2022
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8. Resolution of hepatic fibrosis after ZFN-mediated gene editing in the PiZ mouse model of human α1-antitrypsin deficiency.

Author

Yanfeng Li, Guha, Chandan, Asp, Patrik, Xia Wang, Tchaikovskya, Tatyana L., Kim, Kenneth, Mendel, Matthew, Cost, Gregory J., Perlmutter, David H., Roy-Chowdhury, Namita, Fox, Ira J., Conway, Anthony, and Roy-Chowdhury, Jayanta

Subjects
HEPATIC fibrosis, GENOME editing, LABORATORY mice, ANIMAL disease models, RECOMBINANT viruses, HIGH cholesterol diet, GENE targeting
Abstract

Background: α1-antitrypsin deficiency is most commonly caused by a mutation in exon-7 of SERPINA1 (SA1-ATZ), resulting in hepatocellular accumulation of a misfolded variant (ATZ). Human SA1-ATZ-transgenic (PiZ) mice exhibit hepatocellular ATZ accumulation and liver fibrosis. We hypothesized that disrupting the SA1-ATZ transgene in PiZ mice by in vivo genome editing would confer a proliferative advantage to the genome-edited hepatocytes, enabling them to repopulate the liver. Methods: To create a targeted DNA break in exon-7 of the SA1-ATZ transgene, we generated 2 recombinant adeno-associated viruses (rAAV) expressing a zinc-finger nuclease pair (rAAV-ZFN), and another rAAV for gene correction by targeted insertion (rAAV-TI). PiZmice were injected i.v. with rAAV-TI alone or the rAAV-ZFNs at a low (7.5 x 1010vg/mouse, LD) or a high dose (1.5x1011vg/mouse, HD), with or without rAAV-TI. Two weeks and 6 months after treatment, livers were harvested for molecular, histological, and biochemical analyses. Results: Two weeks after treatment, deep sequencing of the hepatic SA1-ATZ transgene pool showed 6%±3% or 15%±4% nonhomologous end joining in mice receiving LD or HD rAAV-ZFN, respectively, which increased to 36%±12% and 36%±12%, respectively, 6 months after treatment. Two weeks postinjection of rAAV-TI with LD or HD of rAAV-ZFN, repair by targeted insertion occurred in 0.10%±0.09% and 0.25%±0.14% of SA1-ATZ transgenes, respectively, which increased to 5.2%±5.0% and 33%±13%, respectively, 6 months after treatment. Six months after rAAV-ZFN administration, there was a marked clearance of ATZ globules from hepatocytes, and resolution of liver fibrosis, along with reduction of hepatic TAZ/WWTR1, hedgehog ligands, Gli2, a TIMP, and collagen content. Conclusions: ZFN-mediated SA1-ATZ transgene disruption provides a proliferative advantage to ATZ-depleted hepatocytes, enabling them to repopulate the liver and reverse hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Published
2023
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9. Isogenic human cell lines for drug discovery: regulation of target gene expression by engineered zinc-finger protein transcription factors

Author

Liu, Pei-Qi, Tan, Siyuan, Mendel, Matthew C., Murrills, Richard J., Bhat, Bheem M., Schlag, Brian, Samuel, Rachelle, Matteo, Jeanne J., de la Rosa, Ragan, Howes, Katherine, Reik, Andreas, Young, Kathleen, and Gregory, Philip D.

Subjects
Gene expression -- Research, Protein research -- Research, Genetic transcription -- Research, Biological sciences, Research
Abstract

Isogenic cell lines differing only in the expression of the protein of interest provide the ideal platform for cell-based screening. However, related natural lines differentially expressing the therapeutic target of [...]

Published
2005

11. The assessment of complexity of representations of people using TAT and interview data

Author

Leigh, Janet, Westen, Drew, Barends, Alex, Mendel, Matthew J., and Byers, Steven

Subjects
Thematic apperception test -- Usage, Mental representation -- Research, Personality -- Research, Interviews -- Usage, Psychology and mental health
Abstract

The complexity of mental representations of self and others is a central dimension of personality structure and interpersonal functioning. The richness, differentiation, and integration of representations develops throughout childhood and adolescence and differs among individuals and among various psychopathological populations. The nature and development of mental representations is central to object relations theories in psychoanalysis, and has been receiving empirical attention in the social cognition literature. This article reports the development of instruments for measuring the complexity of mental representations from narrative data, based on an integration of object relations and social cognition research. The present study provides preliminary support for the validity of two measures, one for use with the TAT, and the other for use with interview data such as research interviews, psychotherapy transcripts, and early memories.

Published
1992

15. Object Relations Disturbances in Sexually Abused Males

Author

MORRELL, BARBARA, MENDEL, MATTHEW P., and FISCHER, LANE

Subjects
Family violence -- Psychological aspects, Child sexual abuse -- Psychological aspects, Law, Psychology and mental health, Sociology and social work
Abstract

The relationship between object relations and child sexual abuse, physical abuse, and separation from parents was investigated in a clinical sample of 120 adult males with a history of sexual abuse, using the Bell Object Relations Reality Testing Inventory. Variables included gender of and relationship to perpetrator, age of onset, severity, frequency, duration, and number of abusers. Males with a history of abuse demonstrated greater object relations disturbances than the norm, scoring significantly higher on all object relations subscales. Disturbances in object relations were predicted by several sexual abuse variables, including abuse by a male, by both a male and female, by a relative, and by a stranger; and duration, frequency, and severity of abuse. Specific object relations problems were predicted by different patterns of sexual abuse. The implications of findings are discussed in relation to object relations theory, clinical applications for male victims, and future research.

Published
2001

17. Allele-selective transcriptional repression of mutant HTTfor the treatment of Huntington’s disease

Author

Zeitler, Bryan, Froelich, Steven, Marlen, Kimberly, Shivak, David A, Yu, Qi, Li, Davis, Pearl, Jocelynn R, Miller, Jeffrey C, Zhang, Lei, Paschon, David E, Hinkley, Sarah J, Ankoudinova, Irina, Lam, Stephen, Guschin, Dmitry, Kopan, Lexi, Cherone, Jennifer M, Nguyen, Hoang-Oanh B, Qiao, Guijuan, Ataei, Yasaman, Mendel, Matthew C, Amora, Rainier, Surosky, Richard, Laganiere, Josee, Vu, B Joseph, Narayanan, Anand, Sedaghat, Yalda, Tillack, Karsten, Thiede, Christina, Gärtner, Annette, Kwak, Seung, Bard, Jonathan, Mrzljak, Ladislav, Park, Larry, Heikkinen, Taneli, Lehtimäki, Kimmo K, Svedberg, Marie M, Häggkvist, Jenny, Tari, Lenke, Tóth, Miklós, Varrone, Andrea, Halldin, Christer, Kudwa, Andrea E, Ramboz, Sylvie, Day, Michelle, Kondapalli, Jyothisri, Surmeier, D James, Urnov, Fyodor D, Gregory, Philip D, Rebar, Edward J, Muñoz-Sanjuán, Ignacio, and Zhang, H Steve

Abstract

Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG trinucleotide expansion in the huntingtingene (HTT), which codes for the pathologic mutant HTT (mHTT) protein. Since normal HTT is thought to be important for brain function, we engineered zinc finger protein transcription factors (ZFP-TFs) to target the pathogenic CAG repeat and selectively lower mHTT as a therapeutic strategy. Using patient-derived fibroblasts and neurons, we demonstrate that ZFP-TFs selectively repress >99% of HD-causing alleles over a wide dose range while preserving expression of >86% of normal alleles. Other CAG-containing genes are minimally affected, and virally delivered ZFP-TFs are active and well tolerated in HD neurons beyond 100 days in culture and for at least nine months in the mouse brain. Using three HD mouse models, we demonstrate improvements in a range of molecular, histopathological, electrophysiological and functional endpoints. Our findings support the continued development of an allele-selective ZFP-TF for the treatment of HD.

Published
2019
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18. Non-viral Delivery of Zinc Finger Nuclease mRNA Enables Highly Efficient In VivoGenome Editing of Multiple Therapeutic Gene Targets

Author

Conway, Anthony, Mendel, Matthew, Kim, Kenneth, McGovern, Kyle, Boyko, Alisa, Zhang, Lei, Miller, Jeffrey C., DeKelver, Russell C., Paschon, David E., Mui, Barbara L., Lin, Paulo J.C., Tam, Ying K., Barbosa, Chris, Redelmeier, Tom, Holmes, Michael C., and Lee, Gary

Abstract

It has previously been shown that engineered zinc finger nucleases (ZFNs) can be packaged into adeno-associated viruses (AAVs) and delivered intravenously into mice, non-human primates, and most recently, humans to induce highly efficient therapeutic genome editing in the liver. Lipid nanoparticles (LNPs) are synthetic delivery vehicles that enable repeat administration and are not limited by the presence of preexisting neutralizing antibodies in patients. Here, we show that mRNA encoding ZFNs formulated into LNP can enable >90% knockout of gene expression in mice by targeting the TTRor PCSK9gene, at mRNA doses 10-fold lower than has ever been reported. Additionally, co-delivering mRNA-LNP containing ZFNs targeted to intron 1 of the ALBlocus with AAV packaged with a promoterless human IDSor FIXtherapeutic transgene can result in high levels of targeted integration and subsequent therapeutically relevant levels of protein expression in mice. Finally, we show repeat administration of ZFN mRNA-LNP after a single AAV donor dose results in significantly increased levels of genome editing and transgene expression compared to a single dose. These results demonstrate LNP-mediated ZFN mRNA delivery can drive highly efficient levels of in vivogenome editing and can potentially offer a new treatment modality for a variety of diseases.

Published
2019
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19. 77. Clinical Scale Zinc Finger Nuclease (ZFN)-Driven Gene-Editing of PD-1 in Tumor Infiltrating Lymphocytes (TIL) for the Potential Treatment of Metastatic Melanoma

Author

Beane, Joal D., primary, Lee, Gary, additional, Zheng, Zhili, additional, Gandhi, Nimisha, additional, Abate-Daga, Daniel, additional, Bharathan, Mini, additional, Black, Mary, additional, Mendel, Matthew, additional, Yu, Zhiya, additional, Kassim, Sadik H., additional, Chandran, Smita, additional, Giedlin, Martin A., additional, Ando, Dale, additional, Rebar, Ed, additional, Reik, Andreas, additional, Holmes, Michael C., additional, Gregory, Philip D., additional, Restifo, Nicholas P., additional, Rosenberg, Steven A., additional, Morgan, Richard A., additional, and Feldman, Steven A., additional

Published
2015
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20. 115. Correction of the Sickle-Cell Disease Mutation in Human Hematopoietic Stem/Progenitor Cells

Author

Hoban, Megan D., primary, Mendel, Matthew C., additional, Romero, Zulema, additional, Kaufman, Michael L., additional, Joglekar, Alok V., additional, Ho, Michelle, additional, Lumaquin, Dianne, additional, Gray, David, additional, Lill, Georgia R., additional, Cooper, Aaron R., additional, Urbinati, Fabrizia, additional, Senadheera, Shantha, additional, Zhu, Allen, additional, Liu, Pei-Qi, additional, Paschon, David E., additional, Zhang, Lei, additional, Rebar, Edward J., additional, Wilber, Andrew, additional, Wang, Xiaoyan, additional, Gregory, Philip D., additional, Holmes, Michael C., additional, Reik, Andreas, additional, Hollis, Roger P., additional, Kohn, Donald B., additional, and Cost, Gregory J., additional

Published
2015
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21. Clinical scale zinc finger nuclease (ZFN)-driven gene-editing of PD-1 in tumor infiltrating lymphocytes (TIL) for the potential treatment of metastatic melanoma

Author

Beane, Joal D, primary, Lee, Gary K, additional, Zheng, Zhili, additional, Gandhi, Nimisha, additional, Abate-Daga, Daniel, additional, Bharathan, Mini, additional, Black, Mary, additional, Mendel, Matthew, additional, Yu, Zhiya, additional, Kassim, Sadik H, additional, Chandran, Smita, additional, Giedlin, Martin, additional, Ando, Dale, additional, Rebar, Ed, additional, Reik, Andreas, additional, Holmes, Michael, additional, Gregory, Philip D, additional, Restifo, Nicholas P, additional, Rosenberg, Steven A, additional, Morgan, Richard A, additional, and Feldman, Steven A, additional

Published
2014
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23. Targeted Killing of Glioblastoma Multiforme In Vivo by IL-13 Zetakine Redirected CTLs Made Glucocorticoid Resistant with Zinc Finger Nucleases.

Author

Reik, Andreas, primary, Holmes, Michael C., primary, Zhou, Yuanyue, primary, Mendel, Matthew, primary, Liu, Pei-Qi, primary, Lee, Gary, primary, Paschon, David, primary, Rebar, Edward, primary, Ando, Dale, primary, DiGiusto, David, primary, Gregory, Philip D., primary, and Jensen, Michael C., primary

Published
2007
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24. “Designer” Cells for Cellular Immunotherapy: Zinc Finger Nuclease (ZFN) Stimulated Targeted Recombination for the Simultaneous Disruption of the Endogenous Glucocorticoid Receptor and Site-Specific Addition of the IL13-Zetakine.

Author

Reik, Andreas, primary, Holmes, Michael C., additional, Urnov, Fyodor D., additional, Zhou, Yuanyue, additional, Mendel, Matthew, additional, Liu, Pei-Qi, additional, Moehle, Erica, additional, Rebar, Edward J., additional, Miller, Jeffrey C., additional, Ando, Dale, additional, Gregory, Philip D., additional, and Jensen, Michael, additional

Published
2006
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25. Isogenic Human Cell Lines for Drug Discovery: Regulation of Target Gene Expression by Engineered Zinc-Finger Protein Transcription Factors

Author

Liu, Pei-Qi, primary, Tan, Siyuan, additional, Mendel, Matthew C., additional, Murrills, Richard J., additional, Bhat, Bheem M., additional, Schlag, Brian, additional, Samuel, Rachelle, additional, Matteo, Jeanne J., additional, de la Rosa, Ragan, additional, Howes, Katherine, additional, Reik, Andreas, additional, Case, Casey C., additional, Bex, Frederick J., additional, Young, Kathleen, additional, and Gregory, Philip D., additional

Published
2005
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26. Cell Lines for Drug Discovery: Elevating Target-Protein Levels Using Engineered Transcription Factors

Author

Liu, Pei-Qi, primary, Morton, Magda F., additional, Reik, Andreas, additional, de la Rosa, Ragan, additional, Mendel, Matthew C., additional, Li, Xiao-Yong, additional, Case, Casey C., additional, Pabo, Carl O., additional, Moreno, Veronica, additional, Kempf, Ashley, additional, Pyati, Jayashree, additional, and Shankley, Nigel P., additional

Published
2004
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29. Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures.

Author

Doyon, Yannick, Vo, Thuy D., Mendel, Matthew C., Greenberg, Shon G., Jianbin Wang, Xia, Danny F., Miller, Jeffrey C., Urnov, Fyodor D., Gregory, Philip D., and Holmes, Michael C.

Subjects
GENETIC research, GENOMICS, NUCLEASES, DNA, YEAST selection, SCISSION (Chemistry)
Abstract

Zinc-finger nucleases (ZFNs) drive efficient genome editing by introducing a double-strand break into the targeted gene. Cleavage is induced when two custom-designed ZFNs heterodimerize upon binding DNA to form a catalytically active nuclease complex. The importance of this dimerization event for subsequent cleavage activity has stimulated efforts to engineer the nuclease interface to prevent undesired homodimerization. Here we report the development and application of a yeast-based selection system designed to functionally interrogate the ZFN dimer interface. We identified critical residues involved in dimerization through the isolation of cold-sensitive nuclease domains. We used these residues to engineer ZFNs that have superior cleavage activity while suppressing homodimerization. The improvements were portable to orthogonal domains, allowing the concomitant and independent cleavage of two loci using two different ZFN pairs. These ZFN architectures provide a general means for obtaining highly efficient and specific genome modification. [ABSTRACT FROM AUTHOR]

Published
2011
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30. Cell Lines for Drug Discovery: Elevating Target-Protein Levels Using Engineered Transcription Factors

Author

Liu, Pei-Qi, Morton, Magda F., Reik, Andreas, de la Rosa, Ragan, Mendel, Matthew C., Li, Xiao-Yong, Case, Casey C., Pabo, Carl O., Moreno, Veronica, Kempf, Ashley, Pyati, Jayashree, and Shankley, Nigel P.

Abstract

Drug discovery requires high-quality, high-throughput bioassays for lead identification and optimization. These assays are usually based on immortalized cell lines, which express the selected drug target either naturally or as a consequence of transfection with the cDNA encoding the target. Natural untransfected cell lines often fail to achieve the levels of expression required to provide assays of sufficient quality with a high enough signal-to-noise ratio. Unfortunately, the use of cDNA is increasingly restricted, as the sequences for more and more genes become subject to patent restrictions. To overcome these limitations, the authors demonstrate that engineered transcription factors with Cys2-His2zinc finger DNA-binding domains can be used to effectively activate an endogenous gene of interest without the use of isolated cDNA of the target gene. Using this approach, the authors have generated a cell line that provides a high-quality and pharmacologically validated G-protein-coupled receptor bioassay. In principle, this technology is applicable to any gene of pharmaceutical importance in any cell type. (Journal of Biomolecular Screening2004:44-51)

Published
2004
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31. The impact of sexual abuse upon males.

Author

Mendel, Matthew Parynik

Subjects
Child Sexual Abuse, Impact, Males, Men
Abstract

The sexual abuse of male children is an under-recognized problem. There has been scant research into the long-term impact of sexual abuse upon males. Especially little is known about factors which are associated with later disturbance. A clinical sample of 124 men completed questionnaires which included several measures of psychological functioning and a sexual abuse history. The sample was characterized by a preponderance of intrafamilial abuse and multiple perpetration. The incidence of female perpetrators was much higher than found in case-report studies. The relationships among various factors associated with the abuse, psychiatric history, and current psychological functioning were assessed. Outcome measures included a symptom checklist; attributions about the benevolence of the world; a self-esteem scale; self-reports of sexual adjustment and satisfaction; and history of psychiatric hospitalization, psychotropic medication, and suicide attempts. Several factors were associated with each of the indices of negative outcome. Poor psychosocial functioning was predicted by the following factors: abuse of earlier onset, longer duration, and greater severity; abuse by a member of the immediate family, abuse by a male; multiple abusers; drug use by perpetrator; and the presence of physical abuse. The significance of substance abuse and physical abuse along with the sexual abuse leads the author to argue for a broader view of child sexual abuse, integrating other forms of family dysfunction which may co-occur. A subsample of participants were interviewed regarding the impact of their childhood sexual abuse. It was uniformly perceived as severely damaging to most aspects of their lives. Issues which appear to be of particular salience to male survivors are gender shame: a feeling of repugnance regarding men and oneself as a man; a powerful sense of dissonance, with concomitant difficulty integrating one's role expectations as a male with one's experience of victimization; doubts and confusion regarding one's sexual orientation; and fear that one will repeat the cycle of abuse. The author argues that increased attention to and acknowledgment of male victimization is the best way to decrease the incidence of male perpetration.

Published
1992

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