%0 Journal Article %~ PubMed %A Morris, Brian J %A Wiswell, Thomas E %T Circumcision and Lifetime Risk of Urinary Tract Infection: A Systematic Review and Meta-analysis. %B Journal of Urology %D 2013 %C United States %I Elsevier Inc. %V 189 %N 6 %P 2118-2124 %@ 0022-5347 %X %Z FOR Codes: 111716 60502 10499 %0 Journal Article %~ PubMed %A Morris, Brian J %A Krieger, John N %A Kigozi, Godfrey %T Male circumcision decreases penile sensitivity as measured in a large cohort. %B BJU International %D 2013 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 111 %N 5 %P E269-E270 %@ 1464-410X %X %Z FOR Codes: 111404 111799 10402 %0 Journal Article %~ PubMed %A Morris, Brian J %T Seven sirtuins for seven deadly diseases of aging. %B Free Radical Biology & Medicine %D 2013 %C United States %I Elsevier Inc. %V 56 %N %P 133-171 %@ 0891-5849 %X %Z FOR Codes: 110105 60104 110308 %0 Journal Article %~ PubMed %A Morris, Brian J %A Waskett, Jake H %A Banerjee, Joya %A Wamai, Richard G %A Tobian, Aaron Ar %A Gray, Ronald H %A Bailis, Stefan A %A Bailey, Robert C %A Klausner, Jeffrey D %A Willcourt, Robin J %A Halperin, Daniel T %A Wiswell, Thomas E %A Mindel, Adrian %T A 'snip' in time: what is the best age to circumcise? %B BMC Pediatrics %D 2012 %C United Kingdom %I BioMed Central Ltd. %V 12 %N 1 %P 20 %@ 1471-2431 %X ABSTRACT: BACKGROUND: Circumcision is a common procedure, but regional and societal attitudes differ on whether there is a need for a male to be circumcised and, if so, at what age. This is an important issue for many parents, but also paediatricians, other doctors, policy makers, public health authorities, medical bodies, and males themselves. DISCUSSION: We show here that infancy is an optimal time for clinical circumcision because an infant''s low mobility facilitates the use of local anesthesia, sutures are not required, healing is quick, cosmetic outcome is usually excellent, costs are minimal, and complications are uncommon. The benefits of infant circumcision include prevention of urinary tract infections (a cause of renal scarring), reduction in risk of inflammatory foreskin conditions such as balanoposthitis, foreskin injuries, phimosis and paraphimosis. When the boy later becomes sexually active he has substantial protection against risk of HIV and other viral sexually transmitted infections such as genital herpes and oncogenic human papillomavirus, as well as penile cancer. The risk of cervical cancer in his female partner(s) is also reduced. Circumcision in adolescence or adulthood may evoke a fear of pain, penile damage or reduced sexual pleasure, even though unfounded. Time off work or school will be needed, cost is much greater, as are risks of complications, healing is slower, and stitches or tissue glue must be used. SUMMARY: Infant circumcision is safe, simple, convenient and cost-effective. The available evidence strongly supports infancy as the optimal time for circumcision. %Z FOR Codes: 111716 %0 Journal Article %~ PubMed %A Klausner, Jeffrey D %A Morris, Brian J %T Benefits of male circumcision. %B Journal of the American Medical Association %D 2012 %C United States %I American Medical Association %V 307 %N 5 %P 455-456 %@ 1538-3598 %X %Z FOR Codes: 111603 %0 Journal Article %~ PubMed %A Morris, B J %A Wamai, R G %T Biological basis for the protective effect conferred by male circumcision against HIV infection. %B International Journal of STD & AIDS %D 2012 %C United Kingdom %I Royal Society of Medicine Press Ltd. %V 23 %N 3 %P 153-159 %@ 0956-4624 %X Here we provide an up-to-date review of research that explains why uncircumcised men are at higher risk of HIV infection. The inner foreskin is a mucosal epithelium deficient in protective keratin, yet rich in HIV target cells. Soon after sexual exposure to infected mucosal secretions of a HIV-positive partner, infected T-cells from the latter form viral synapses with keratinocytes and transfer HIV to Langerhans cells via dendrites that extend to just under the surface of the inner foreskin. The Langerhans cells with internalized HIV migrate to the basal epidermis and then pass HIV on to T-cells, thus leading to the systemic infection that ensues. Infection is exacerbated in inflammatory states associated with balanoposthitis, the presence of smegma and ulceration - including that caused by infection with herpes simplex virus type 2 and some other sexually transmitted infections (STIs). A high foreskin surface area and tearing of the foreskin or associated frenulum during sexual intercourse also facilitate HIV entry. Thus, by various means, the foreskin is the primary biological weak point that permits HIV infection during heterosexual intercourse. The biological findings could explain why male circumcision protects against HIV infection. %Z FOR Codes: 60199 111716 60502 %0 Journal Article %~ PubMed %A Morris, Brian J %T Boyle and hill's circumcision 'phallusies'. %B BJU International %D 2012 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 110 %N 3 %P E153-154 %@ 1464-410X %X %Z FOR Codes: 111403 111799 110899 %0 Journal Article %~ PubMed %A Morris, Brian J %A Waskett, Jake H %T Circumcision reduces prostate cancer risk. %B Asian Journal of Andrology %D 2012 %C United States %I Nature Publishing Group %V 14 %N 5 %P 661-662 %@ 1745-7262 %X %Z FOR Codes: 111299 111716 110899 %0 Journal Article %A Morris, Brian %A Waskett, Jake H. %T Claims That Circumcision Increases Alexithymia and Erectile Dysfunction Are Unfounded: A Critique of Bollinger and Van Howe's "Alexithymia and Circumcision Trauma: A Preliminary Investigation" %B International Journal of Men's Health %D 2012 %C United States %I Men's Studies Press %V 11 %N 2 %P 177-181 %@ 1532-6306 %X %Z FOR Codes: 111699 %0 Journal Article %A Wamai, Richard G %A Morris, Brian %A Waskett , Jake H %A Green, Edward C %A Banerjee, Joya %A Bailey, Robert C %A Klausner , Jeffrey D %A Sokal, David C %A Hankins, Catherine A %T Criticisms of African trials fail to withstand scrutiny: Male circumcision does prevent HIV infection %B Journal of Law and Medicine %D 2012 %C Australia %I Lawbook Co. %V 20 %N 1 %P 93-123 %@ 1320-159X %X %Z FOR Codes: 110309 %0 Book Section %A Morris, Brian %A Cox, Guy %T Current Medical Evidence Supports Male Circumcision %B Surgical Guide to Circumcision %D 2012 %C Germany %I Springer-Verlag %V %N %P 201-231 %@ 9781447128571 %E Bolnick, David A. %E Koyle, Martin %E Yosha, Assaf %E Bolnick, David A. %E Koyle, Martin %E Yosha, Assaf %X %Z FOR Codes: 110323 111716 %0 Journal Article %A Morris, Brian %T Die medizinischen vorteile der beschneidung [The medical benefits of circumcision] %B W+N. Kulturpolitische Nachrichten des Fachverbandes "Werte und Normen" in Niedersachen e.V. [Cultural Policy News of the Association "Values and Norms" in Lower Saxony eV] %D 2012 %C Germany %I Verlag Traugott Bautz %V 2012/2 %N %P 6-21 %@ 1618-1557 %X %Z FOR Codes: 111716 %0 Journal Article %~ PubMed %A Morris, Brian J %A Waskett, Jake H %A Gray, Ronald H %T Does sexual function survey in Denmark offer any support for male circumcision having an adverse effect? %B International Journal of Epidemiology %D 2012 %C United Kingdom, Egypt %I Oxford University Press %V 41 %N 1 %P 310-314 %@ 0300-5771 %X %Z FOR Codes: 111706 %0 Journal Article %~ PubMed %A Wang, Yu %A Pringle, Kirsty G %A Sykes, Shane D %A Marques, Francine Z %A Morris, Brian J %A Zakar, Tamas %A Lumbers, Eugenie R %T Fetal sex affects expression of renin-angiotensin system components in term human decidua. %B Endocrinology %D 2012 %C United States %I The Endocrine Society %V 153 %N 1 %P 462-468 %@ 0013-7227 %X The maternal decidua expresses the genes of the renin-angiotensin system (RAS). Human decidua was collected at term either before labor (i.e. cesarean delivery) or after spontaneous labor. The mRNA for prorenin (REN), prorenin receptor (ATP6AP2), angiotensinogen (AGT), angiotensin-converting enzymes 1 and 2 (ACE1 and ACE2), angiotensin II type 1 receptor (AGTR1), and angiotensin 1-7 receptor (MAS1) were measured by quantitative real-time RT-PCR. Decidual explants were cultured in duplicate for 24 and 48 h, and all RAS mRNA, and the secretion of prorenin, angiotensin II, and angiotensin 1-7 was measured using quantitative real-time RT-PCR, ELISA, and radioimmunoassay, respectively. In the decidua collected before labor, REN mRNA levels were higher if the fetus was female. In addition, REN, ATP6AP2, AGT, and MAS1 mRNA abundance was greater in decidual explants collected from women carrying a female fetus, as was prorenin protein. After 24 h, ACE1 mRNA was higher in the decidual explants from women with a male fetus, whereas after 48 h, both ACE1 and ACE2 mRNA was higher in decidual explants from women with a female fetus. Angiotensin II was present in all explants, but angiotensin 1-7 levels often registered below the lower limits of sensitivity for the assay. After labor, decidua, when compared with nonlaboring decidua, demonstrated lower REN expression when the fetus was female. Therefore, the maternal decidual RAS is regulated in a sex-specific manner, suggesting that it may function differently when the fetus is male than when it is female. %Z FOR Codes: 111402 60199 110306 %0 Journal Article %A Morris, Brian %A Wodak, Alex D %A Mindel, Adrian %A Schrieber, Leslie %A Duggan, Karen A %A Dilley, Anthony %A Willcourt, Robin J %A Lowy, Michael %A Cooper, David A %A Lumbers, Eugenie R %A Russell, C Terry %A Leeder, Stephen %T Infant male circumcision: An evidence-based policy statement %B Open Journal of Preventive Medicine %D 2012 %C United States %I Scientific Research Publishing, Inc. %V 2 %N 1 %P 79-92 %@ 2162-2477 %X %Z FOR Codes: 111716 %0 Journal Article %~ PubMed %A Bates, B %A Morris, B J %T Legal arguments opposing infant male circumcision are flawed. %B Internal Medicine Journal %D 2012 %C Australia, United Kingdom, Netherlands, United States %I Wiley-Blackwell Publishing Asia %V 42 %N 11 %P 1281-1282 %@ 1445-5994 %X %Z FOR Codes: 111403 111716 111499 %0 Journal Article %~ PubMed %A Marques, Francine Z %A Morris, Brian J %T Letter by Marques and Morris Regarding Article, "Signature microRNA expression profile of essential hypertension and its novel link to human cytomegalovirus infection". %B Circulation %D 2012 %C United States %I Lippincott Williams & Wilkins %V 125 %N 5 %P e337 %@ 0009-7322 %X %Z FOR Codes: 110106 %0 Journal Article %~ PubMed %A Marques, Francine Z %A Morris, Brian J %T Neurogenic hypertension: revelations from genome-wide gene expression profiling. %B Current Hypertension Reports %D 2012 %C United States %I Springer Healthcare %V 14 %N 6 %P 485-491 %@ 1534-3111 %X %Z FOR Codes: 60405 %0 Journal Article %A Morris, Brian %A Castellsague, Xavier %A Wiswell, Thomas E %A Gray, Ronald H %A Bailey, Robert C %A Hankins, Catherine A %A Tobian, Aaron AR %A Weiss, Helen J %A Klausner, Jeffrey D %A Halperin, Daniel T %A Quinn, Thomas C %T New Circumcision Policy Welcomed %B Pediatrics %D 2012 %C United States %I American Academy of Pediatrics %V 130 %N 3 %P e756-e785 %@ 1098-4275 %X %Z FOR Codes: 111403 %0 Journal Article %A Morris, Brian %T Re: Technical Report on Male Circumcision- Time to accept the evidence in favor! %B Pediatrics %D 2012 %C United States %I American Academy of Pediatrics %V 130 %N 3 %P e756-e785 %@ 1098-4275 %X %Z FOR Codes: 111403 %0 Journal Article %~ PubMed %A Morris, B J %A Wodak, A D %A Mindel, A %A Schrieber, L %A Duggan, K A %A Dilley, A %A Willcourt, R J %A Lowy, M %A Cooper, D A %T Reply. %B Internal Medicine Journal %D 2012 %C Australia %I Wiley-Blackwell Publishing Asia %V 42 %N 11 %P 1279-1280 %@ 1445-5994 %X %Z FOR Codes: 1117 %0 Journal Article %~ PubMed %A Dilley, A %A Morris, B J %T Reply. %B Internal Medicine Journal %D 2012 %C Australia, United Kingdom, Netherlands, United States %I Wiley-Blackwell Publishing Asia %V 42 %N 11 %P 1277-1278 %@ 1445-5994 %X %Z FOR Codes: 111403 111704 60501 %0 Journal Article %~ PubMed %A Morris, Brian J %A Bailey, Robert C %A Klausner, Jeffrey D %A Leibowitz, Arleen %A Wamai, Richard G %A Waskett, Jake H %A Banerjee, Joya %A Halperin, Daniel T %A Zoloth, Laurie %A Weiss, Helen A %A Hankins, Catherine A %T Review: A critical evaluation of arguments opposing male circumcision for HIV prevention in developed countries. %B AIDS Care %D 2012 %C United Kingdom %I Routledge %V 24 %N 12 %P 1565-1575 %@ 1360-0451 %X Abstract A potential impediment to evidence-based policy development on medical male circumcision (MC) for HIV prevention in all countries worldwide is the uncritical acceptance by some of arguments used by opponents of this procedure. Here we evaluate recent opinion-pieces of 13 individuals opposed to MC. We find that these statements misrepresent good studies, selectively cite references, some containing fallacious information, and draw erroneous conclusions. In marked contrast, the scientific evidence shows MC to be a simple, low-risk procedure with very little or no adverse long-term effect on sexual function, sensitivity, sensation during arousal or overall satisfaction. Unscientific arguments have been recently used to drive ballot measures aimed at banning MC of minors in the USA, eliminate insurance coverage for medical MC for low-income families, and threaten large fines and incarceration for health care providers. Medical MC is a preventative health measure akin to immunisation, given its protective effect against HIV infection, genital cancers and various other conditions. Protection afforded by neonatal MC against a diversity of common medical conditions starts in infancy with urinary tract infections and extends throughout life. Besides protection in adulthood against acquiring HIV, MC also reduces morbidity and mortality from multiple other sexually transmitted infections (STIs) and genital cancers in men and their female sexual partners. It is estimated that over their lifetime one-third of uncircumcised males will suffer at least one foreskin-related medical condition. The scientific evidence indicates that medical MC is safe and effective. Its favourable risk/benefit ratio and cost/benefit support the advantages of medical MC. %Z FOR Codes: 111716 110804 111708 %0 Journal Article %~ PubMed %A Morris, Brian J %A Mindel, Adrian %A Tobian, Aaron Ar %A Hankins, Catherine A %A Gray, Ronald H %A Bailey, Robert C %A Bosch, Xavier %A Wodak, Alex D %T Should Male Circumcision be Advocated for Genital Cancer Prevention? %B Asian Pacific Journal of Cancer Prevention %D 2012 %C Thailand %I Asian Pacific Organization for Cancer Prevention %V 13 %N 9 %P 4839-4842 %@ 1513-7368 %X %Z FOR Codes: 111299 111716 111402 %0 Journal Article %~ PubMed %A Morris, B J %A Wodak, A D %A Mindel, A %A Schrieber, L %A Duggan, K A %A Dilley, A %A Willcourt, R J %A Lowy, M %A Cooper, D A %T The 2010 Royal Australasian College of Physicians' policy statement 'Circumcision of infant males' is not evidence based. %B Internal Medicine Journal %D 2012 %C Australia, United Kingdom, Netherlands, United States %I Wiley-Blackwell Publishing Asia %V 42 %N 7 %P 822-828 %@ 1445-5994 %X Infant male circumcision (MC) is an important issue guided by Royal Australasian College of Physicians (RACP) policy. Here we analytically review the RACP''s 2010 policy statement ''Circumcision of infant males''. Comprehensive evaluation in the context of published research was used. We find that the Statement is not a fair and balanced representation of the literature on MC. It ignores, downplays, obfuscates or misrepresents the considerable evidence attesting to the strong protection MC affords against childhood urinary tract infections, sexually transmitted infections (human immunodeficiency virus, human papilloma virus, herpes simplex virus type 2, trichomonas and genital ulcer disease), thrush, inferior penile hygiene, phimosis, balanoposthitis and penile cancer, and in women protection against human papilloma virus, herpes simplex virus type 2, bacterial vaginosis and cervical cancer. The Statement exaggerates the complication rate. Assertions that ''the foreskin has a functional role'' and ''is a primary sensory part of the penis'' are not supported by research, including randomised controlled trials. Instead of citing these and meta-analyses, the Statement selectively cites poor quality studies. Its claim, without support from a literature-based risk-benefit analysis, that the currently available evidence does ''not warrant routine infant circumcision in Australia and New Zealand'' is misleading. The Statement fails to explain that performing MC in the neonatal period using local anaesthesia maximises benefits, safety, convenience and cost savings. Because the RACP''s policy statement is not a fair and balanced representation of the current literature, it should not be used to guide policy. In the interests of public health and individual well-being, an extensive, comprehensive, balanced review of the scientific literature and a risk-benefit analysis should be conducted to formulate policy. %Z FOR Codes: 111403 111799 110899 111403 111799 110899 %0 Book Section %A Cox, Guy %A Morris, Brian %T Why Circumcision: From Prehistory to the Twenty-First Century %B Surgical Guide to Circumcision %D 2012 %C Germany %I Springer-Verlag %V %N %P 243-260 %@ 9781447128571 %E Bolnick, David A. %E Koyle, Martin %E Yosha, Assaf %E Bolnick, David A. %E Koyle, Martin %E Yosha, Assaf %X %Z FOR Codes: 111799 %0 Journal Article %~ PubMed %A Wamai, R %A Morris, B J %T 'How to contain generalized HIV epidemics' article misconstrues the evidence. %B International Journal of STD & AIDS %D 2011 %C United Kingdom %I Royal Society of Medicine Press Ltd. %V 22 %N 7 %P 415-416 %@ 0956-4624 %X %Z FOR Codes: 111706 %0 Journal Article %~ PubMed %A Morris, Brian J %T A "SNP in time" for SCNN1G to join the "highly likely" list of genes for essential hypertension. %B Hypertension %D 2011 %C United States %I Lippincott Williams & Wilkins %V 58 %N 6 %P 996-997 %@ 0194-911X %X %Z FOR Codes: 60408 110201 110311 %0 Journal Article %~ PubMed %A Banerjee, Joya %A Klausner, Jeffrey D %A Halperin, Daniel T %A Wamai, Richard %A Schoen, Edgar J %A Moses, Stephen %A Morris, Brian J %A Bailis, Stefan A %A Venter, Francois %A Martinson, Neil %A Coates, Thomas J %A Gray, Glenda %A Bowa, Kasonde %T Circumcision denialism unfounded and unscientific. %B American Journal of Preventive Medicine %D 2011 %C United States %I Elsevier Inc. %V 40 %N 3 %P e11-12; author reply e13-4 %@ 0749-3797 %X %Z FOR Codes: 111716 60502 110309 60599 110309 %0 Journal Article %A Morris, Brian %A Waskett, Jake H %A Gray, Ronald H %A Halperin, Daniel T %A Wamai, Richard %A Auvert, Bertran %A Klausner, Jeffery D %T Exposé of misleading claims that male circumcision will increase HIV infections in Africa %B Journal of Public Health Africa %D 2011 %C Italy %I Pagepress %V 2 %N e28 %P 117-122 %@ 2038-9930 %X %Z FOR Codes: 111716 %0 Journal Article %~ PubMed %A Marques, Francine Z %A Campain, Anna E %A Tomaszewski, Maciej %A Zukowska-Szczechowska, Ewa %A Yang, Yee Hwa J %A Charchar, Fadi J %A Morris, Brian J %T Gene expression profiling reveals renin mRNA overexpression in human hypertensive kidneys and a role for microRNAs. %B Hypertension %D 2011 %C United States %I Lippincott Williams & Wilkins %V 58 %N 6 %P 1093-1098 %@ 0194-911X %X The kidney has long been invoked in the etiology of essential hypertension. This could involve alterations in expression of specific genes and microRNAs (miRNAs). The aim of the present study was to identify, at the transcriptome-wide level, mRNAs and miRNAs that were differentially expressed between kidneys of 15 untreated hypertensive and 7 normotensive white male subjects of white European ancestry. By microarray technology we found 14 genes and 11 miRNAs that were differentially expressed in the medulla. We then selected and confirmed by real-time quantitative PCR expression differences for NR4A1, NR4A2, NR4A3, PER1, and SIK1 mRNAs and for the miRNAs hsa-miR-638 and hsa-let-7c. Luciferase reporter gene experiments in human kidney (HEK293) cells confirmed the predicted binding of hsa-let-7c to the 3'' untranslated region of NR4A2 mRNA. In the renal cortex we found differential expression of 46 genes and 13 miRNAs. We then confirmed expression differences for AIFM1, AMBP, APOE, CD36, EFNB1, NDUFAF1, PRDX5, REN, RENBP, SLC13A1, STX4, and TNNT2 mRNAs and for miRNAs hsa-miR-21, hsa-miR-126, hsa-miR-181a, hsa-miR-196a, hsa-miR-451, hsa-miR-638, and hsa-miR-663. Functional experiments in HEK293 cells demonstrated that hsa-miR-663 can bind to the REN and APOE 3'' untranslated regions and can regulate REN and APOE mRNA levels, whereas hsa-miR-181a regulated REN and AIFM1 mRNA. Our data demonstrated for the first time that miRNAs can regulate renin expression. The observed downregulation of 2 miRNAs in hypertension could explain the elevation in intrarenal renin mRNA. Renin, CD36, and other mRNAs, as well as miRNAs and associated pathways identified in the present study, provide novel insights into hypertension etiology. %Z FOR Codes: 110201 60405 60102 %0 Journal Article %~ PubMed %A Marques, Francine Z %A Campain, Anna E %A Davern, Pamela J %A Yang, Yee Hwa J %A Head, Geoffrey A %A Morris, Brian J %T Genes influencing circadian differences in blood pressure in hypertensive mice. %B PloS One %D 2011 %C United States %I Public Library of Science %V 6 %N 4 %P e19203 %@ 1932-6203 %X Essential hypertension is a common multifactorial heritable condition in which increased sympathetic outflow from the central nervous system is involved in the elevation in blood pressure (BP), as well as the exaggerated morning surge in BP that is a risk factor for myocardial infarction and stroke in hypertensive patients. The Schlager BPH/2J mouse is a genetic model of hypertension in which increased sympathetic outflow from the hypothalamus has an important etiological role in the elevation of BP. Schlager hypertensive mice exhibit a large variation in BP between the active and inactive periods of the day, and also show a morning surge in BP. To investigate the genes responsible for the circadian variation in BP in hypertension, hypothalamic tissue was collected from BPH/2J and normotensive BPN/3J mice at the ''peak'' (n???=???12) and ''trough'' (n???=???6) of diurnal BP. Using Affymetrix GeneChip?? Mouse Gene 1.0 ST Arrays, validation by quantitative real-time PCR and a statistical method that adjusted for clock genes, we identified 212 hypothalamic genes whose expression differed between ''peak'' and ''trough'' BP in the hypertensive strain. These included genes with known roles in BP regulation, such as vasopressin, oxytocin and thyrotropin releasing hormone, as well as genes not recognized previously as regulators of BP, including chemokine (C-C motif) ligand 19, hypocretin and zinc finger and BTB domain containing 16. Gene ontology analysis showed an enrichment of terms for inflammatory response, mitochondrial proton-transporting ATP synthase complex, structural constituent of ribosome, amongst others. In conclusion, we have identified genes whose expression differs between the peak and trough of 24-hour circadian BP in BPH/2J mice, pointing to mechanisms responsible for diurnal variation in BP. The findings may assist in the elucidation of the mechanism for the morning surge in BP in essential hypertension. %Z FOR Codes: 110201 60408 110903 %0 Journal Article %~ PubMed %A Marques, Francine Z %A Campain, Anna E %A Davern, Pamela J %A Yang, Yee Hwa J %A Head, Geoffrey A %A Morris, Brian J %T Global identification of the genes and pathways differentially expressed in hypothalamus in early and established neurogenic hypertension. %B Physiological genomics %D 2011 %C United States %I American Physiological Society %V 43 %N 12 %P 766-771 %@ 1531-2267 %X The hypothalamus has an important etiological role in the onset and maintenance of hypertension and stress responses in the Schlager high blood pressure (BP) (BPH/2J) mouse, a genetic model of neurogenic hypertension. Using Affymetrix GeneChip Mouse Gene 1.0 ST Arrays we identified 1,019 hypothalamic genes whose expression differed between 6 wk old BPH/2J and normal BP (BPN/3J) strains, and 466 for 26 wk old mice. Of these, 459 were in 21 mouse BP quantitative trait loci. We validated 46 genes by qPCR. Gene changes that would increase sympathetic outflow at both ages were: Dynll1 encoding dynein light chain LC8-type 1, which physically destabilizes neuronal nitric oxide synthase, decreasing neuronal nitric oxide, and Hcrt encoding hypocretin and Npsr1 encoding neuropeptide S receptor 1, each involved in sympathetic response to stress. At both ages we identified genes for inflammation, such as CC-chemokine ligand 19 (Ccl19), and oxidative stress. Via reactive oxygen species generation, these could contribute to oxidative damage. Other genes identified could be responding to such perturbations. Atp2b1, the major gene from genome-wide association studies of BP variation, was underexpressed in the early phase. Comparison of profiles of young and adult BPH/2J mice, after adjusting for maturation genes, pointed to the proopiomelanocortin-?? gene (Pomc) and neuropeptide Y gene (Npy), among others, as potentially causative. The present study has identified a diversity of genes and possible mechanisms involved in hypertension etiology and maintenance in the hypothalamus of BPH/2J mice, highlighting both common and divergent processes in each phase of the condition. %Z FOR Codes: 110201 60408 110903 %0 Journal Article %~ PubMed %A Wamai, Richard G %A Morris, Brian J %A Bailis, Stefan A %A Sokal, David %A Klausner, Jeffrey D %A Appleton, Ross %A Sewankambo, Nelson %A Cooper, David A %A Bongaarts, John %A de Bruyn, Guy %A Wodak, Alex D %A Banerjee, Joya %T Male circumcision for HIV prevention: current evidence and implementation in sub-Saharan Africa. %B Journal of the International AIDS Society %D 2011 %C United Kingdom %I BioMed Central Ltd. %V 14 %N 1 %P 49 %@ 1758-2652 %X Heterosexual exposure accounts for most HIV transmission in sub-Saharan Africa, and this mode, as a proportion of new infections, is escalating globally. The scientific evidence accumulated over more than 20 years shows that among the strategies advocated during this period for HIV prevention, male circumcision is one of, if not, the most efficacious epidemiologically, as well as cost-wise. Despite this, and recommendation of the procedure by global policy makers, national implementation has been slow. Additionally, some are not convinced of the protective effect of male circumcision and there are also reports, unsupported by evidence, that non-sex-related drivers play a major role in HIV transmission in sub-Saharan Africa. Here, we provide a critical evaluation of the state of the current evidence for male circumcision in reducing HIV infection in light of established transmission drivers, provide an update on programmes now in place in this region, and explain why policies based on established scientific evidence should be prioritized. We conclude that the evidence supports the need to accelerate the implementation of medical male circumcision programmes for HIV prevention in generalized heterosexual epidemics, as well as in countering the growing heterosexual transmission in countries where HIV prevalence is presently low. %Z FOR Codes: 111716 %0 Book Section %A Morris, Brian %A Eley, Chris %T Male circumcision: An appraisal of current instrumentation %B Biomedical Engineering -From Theory to Applications %D 2011 %C Croatia %I InTech %V %N %P 315-354 %@ 9789533076379 %E Fazel-Rezai, Reza %X %Z FOR Codes: 111403 %0 Journal Article %~ PubMed %A Marques, F Z %A Pringle, K G %A Conquest, A %A Hirst, J J %A Markus, M A %A Sarris, M %A Zakar, T %A Morris, B J %A Lumbers, E R %T Molecular characterization of renin-angiotensin system components in human intrauterine tissues and fetal membranes from vaginal delivery and cesarean section. %B Placenta %D 2011 %C United Kingdom %I Elsevier Ltd %V 32 %N 3 %P 214-221 %@ 0143-4004 %X A prorenin-angiotensin system (RAS) could, via the (pro)renin receptor (ATP6AP2), have various effects in human intrauterine tissues, either directly by prorenin/ATP6AP2 cell signaling, or indirectly via angiotensin II and/or angiotensin 1-7. Here we describe RAS components in fetal membranes, decidua and placenta collected at elective cesarean section (non-laboring), after spontaneous delivery (after labor, n = 38), and in myometria (n = 16) from elective (non-laboring) or emergency cesarean (laboring) deliveries. Angiotensinogen (AGT), angiotensin-converting enzyme 1 and 2 (ACE; ACE2), angiotensin receptor 1 and 2 (AGTR1; AGTR2) and angiotensin 1-7 receptor (MAS1) mRNAs were measured by qRT-PCR and proteins were localized by immunohistochemistry. In myometrium, prorenin (REN), ATP6AP2, and downstream signaling proteins zinc finger and BTB domain-containing protein 16 (ZBTB16), transforming growth factor-?1 (TGF?1) and prostaglandin-endoperoxide synthase 2 (PTGS2) mRNAs were also measured. RAS mRNAs, except AGTR1 and AGTR2, were abundant in decidua and lowest in amnion compared to the other tissues. ACE, AGT and PTGS2 mRNAs were higher in laboring than non-laboring myometrium, suggesting that the myometrial RAS is involved in labor. Angiotensinogen and prorenin staining in amnion, chorion and decidua was pervasive despite their mRNAs being low in amnion and chorion. In placenta, prorenin, angiotensinogen and AGTR2 were present in syncytiotrophoblasts, ACE was in fetal endothelium, while ACE2 distribution was diffuse. AGTR1 and AGTR2 mRNAs and proteins were abundant. No differences were evident in the staining patterns with labor. These results are consistent with the hypothesis that fetal vascular ACE might contribute angiotensin II to the fetus, whilst syncytial ACE2 might hypothetically have a role in converting angiotensin II to angiotensin 1-7 in maternal blood. %Z FOR Codes: 111402 60199 110306 60199 110306 %0 Journal Article %~ PubMed %A Morris, Brian J %T Renin, genes, and beyond: 40 years of molecular discoveries in the hypertension field. %B Hypertension %D 2011 %C United States %I Lippincott Williams & Wilkins %V 57 %N 3 %P 538-548 %@ 0194-911X %X %Z FOR Codes: 60199 60405 110299 %0 Journal Article %~ PubMed %A Markus, M Andrea %A Marques, Francine Z %A Morris, Brian J %T Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs. %B PloS One %D 2011 %C United States %I Public Library of Science %V 6 %N 12 %P e28926 %@ 1932-6203 %X Alternative pre-mRNA splicing defects can contribute to, or result from, various diseases, including cancer. Aberrant mRNAs, splicing factors and other RNA processing factors have therefore become targets for new therapeutic interventions. Here we report that the natural polyphenol resveratrol can modulate alternative splicing in a target-specific manner. We transfected minigenes of several alternatively spliceable primary mRNAs into HEK293 cells in the presence or absence of 1, 5, 20 and 50 ??M resveratrol and measured exon levels by semi-quantitative PCR after separation by agarose gel electrophoresis. We found that 20 ??g/ml and 50 ??g/ml of resveratrol affected exon inclusion of SRp20 and SMN2 pre-mRNAs, but not CD44v5 or tau pre-mRNAs. By Western blotting and immunofluorescence we showed that this effect may be due to the ability of resveratrol to change the protein level but not the localization of several RNA processing factors. The processing factors that increased significantly were ASF/SF2, hnRNPA1 and HuR, but resveratrol did not change the levels of RBM4, PTBP1 and U2AF35. By means of siRNA-mediated knockdown we depleted cells of SIRT1, regarded as a major target of resveratrol, and showed that the effect on splicing was not dependent on SIRT1. Our results suggest that resveratrol might be an attractive small molecule to treat diseases in which aberrant splicing has been implicated, and justify more extensive research on the effects of resveratrol on the splicing machinery. %Z FOR Codes: 60109 110105 110499 %0 Journal Article %A Cooper, David A %A Wodak, Alex D %A Morris, Brian %T The case for boosting infant male circumcision in the face of rising heterosexual transmission of HIV – In Reply. (Invited) %B Medical Journal of Australia %D 2011 %C Australia %I Australasian Medical Publishing Company Pty. Ltd %V 194 %N 2 %P 101 %@ 0025-729X %X %Z FOR Codes: 110309 111716 %0 Book Section %A Morris, Brian %A Castellsague, Xavier %T The role of circumcision in preventing STIs %B Sexually Transmitted Infections and Sexually Transmitted Diseases %D 2011 %C Germany %I Springer %V %N %P 715-740 %@ 9783642146626 %E Gross, Gerd %E Tyring, Stephen K %X %Z FOR Codes: 111706 60502 %0 Journal Article %~ PubMed %A Morris, Brian J %A Gray, Ronald H %A Castellsague, Xavier %A Bosch, F Xavier %A Halperin, Daniel T %A Waskett, Jake H %A Hankins, Catherine A %T The strong protective effect of circumcision against cancer of the penis. %B Advances in Urology %D 2011 %C United States %I Hindawi Publishing Corporation %V 2011 %N %P 812368 %@ 1687-6377 %X Male circumcision protects against cancer of the penis, the invasive form of which is a devastating disease confined almost exclusively to uncircumcised men. Major etiological factors are phimosis, balanitis, and high-risk types of human papillomavirus (HPV), which are more prevalent in the glans penis and coronal sulcus covered by the foreskin, as well as on the penile shaft, of uncircumcised men. Circumcised men clear HPV infections more quickly. Phimosis (a constricted foreskin opening impeding the passage of urine) is confined to uncircumcised men, in whom balanitis (affecting 10%) is more common than in circumcised men. Each is strongly associated with risk of penile cancer. These findings have led to calls for promotion of male circumcision, especially in infancy, to help reduce the global burden of penile cancer. Even more relevant globally is protection from cervical cancer, which is 10-times more common, being much higher in women with uncircumcised male partners. Male circumcision also provides indirect protection against various other infections in women, along with direct protection for men from a number of genital tract infections, including HIV. Given that adverse consequences of medical male circumcision, especially when performed in infancy, are rare, this simple prophylactic procedure should be promoted. %Z FOR Codes: 111299 111716 111402 %0 Book Section %A Morris, Brian %T Calorie restriction mimetics and aging %B Calorie Restriction, Ageing and Longevity %D 2010 %C Germany, United Stat %I Springer Science + Business Media B.V. %V %N %P 141-176 %@ 9789048185559 %E Rattan, Suresh I S %E de Cabo, Rafael %E Le Couteur, David %E Everitt, Arthur %X %Z FOR Codes: 111103 %0 Journal Article %~ PubMed %A Morris, Brian J %A Wodak, Alex %T Circumcision survey misleading. %B Australian and New Zealand Journal of Public Health %D 2010 %C Australia %I Wiley-Blackwell Publishing Asia %V 34 %N 6 %P 636-637 %@ 1326-0200 %X %Z FOR Codes: 111716 110804 111404 %0 Journal Article %~ PubMed %A Marques, Francine Z %A Morris, Brian J %T Commentary on resveratrol and hormesis: resveratrol--a hormetic marvel in waiting? %B Human & Experimental Toxicology %D 2010 %C United Kingdom %I Sage Publications Ltd %V 29 %N 12 %P 1026-1028 %@ 1477-0903 %X Hormesis is a phenomenon in which adaptive responses to low doses of otherwise-harmful factors (also called mild stressors) make cells and organisms more robust. In their review, Calabrese et al. provide evidence for resveratrol acting hormetically in different types of human cell lines. The effects of resveratrol represent a ''two-edged sword'' in that it has contrasting effects at low and high doses in healthy and cancerogenous cells. What demarcates a low and a high dose needs to be clarified. Concentrations tested in cell cultures, moreover, may not be relevant to whole organisms. And data from animal models need not apply to humans. Co-morbidities should also be considered. More research is needed to understand the action of resveratrol on all cell types and conditions, and the optimum therapeutic concentration that applies to each of these. Future research needs to determine the dynamics of the effects of resveratrol in different subcellular compartments and the interactions of these. In addition, the interactions between resveratrol, environmental factors, other compounds and medications, diseases and the genetic background of the individual will need to be appreciated in order to gain a complete understanding of the hormetic response of resveratrol. %Z FOR Codes: 110107 110499 111199 %0 Book Section %A Everitt, Arthur %A Heilbronn, Leonie K %A Morris, Brian %A Brown-Borg, Holly M %A Merry, Brian J %A Simpson, Stephen J %A Varady, Krista A %A Masoro, Edward J %A Redman, Leanne M %A Le Couteur, David %T Conclusion: Human Calorie Restriction and Anti-Aging Therapy %B Calorie Restriction, Ageing and Longevity %D 2010 %C Germany, United Stat %I Springer Science + Business Media B.V. %V %N %P 311-318 %@ 9789048185559 %E Rattan, Suresh I S %E de Cabo, Rafael %E Le Couteur, David %E Everitt, Arthur %X %Z FOR Codes: 111103 %0 Journal Article %~ PubMed %A Marques, Francine Z %A Markus, M Andrea %A Morris, Brian J %T Hormesis as a pro-healthy aging intervention in human beings? %B Dose-response : a publication of International Hormesis Society %D 2010 %C United States, Nethe %I International Dose-Response Society %V 8 %N 1 %P 28-33 %@ 1559-3258 %X Hormesis is a phenomenon in which adaptive responses to low doses of otherwise harmful factors (also called mild stressors) make cells and organisms more robust. Aging is a complex and poorly understood process. This review explores the positive effects of hormesis on aging in animal models and human cell cultures, and discusses whether it might apply to humans. As an example, repeated mild heat stress confers anti-aging benefits to normal human cells in culture. Calorie restriction and xenohormetic compounds such as resveratrol, in large part via activation of sirtuins, decrease risk of common age-related conditions, such as cancer, cardiovascular disease, type 2 diabetes, and neurological diseases, so lengthening lifespan. Mild stressors and xenohormetic dietary components have diverse molecular targets and affect many pathways. Despite experimental advances in aging research, findings in humans are still quite limited. Moderate-intensity exercise, weight management and healthy diet ameliorate diseases of aging to increase lifespan and this could involve hormesis. %Z FOR Codes: 110107 110499 111601 %0 Journal Article %~ PubMed %A Gray, Ron H %A Bailey, Robert C %A Morris, Brian J %T Keratinization of the adult male foreskin and implications for male circumcision. %B AIDS %D 2010 %C United States %I Lippincott Williams & Wilkins %V 24 %N 9 %P 1381 %@ 1473-5571 %X %Z FOR Codes: 111716 110303 110804 %0 Journal Article %~ PubMed %A Marques, Francine Z %A Campain, Anna E %A Yang, Yee Hwa J %A Morris, Brian J %T Meta-Analysis of genome-wide gene expression differences in onset and maintenance phases of genetic hypertension. %B Hypertension %D 2010 %C United States %I Lippincott Williams & Wilkins %V 56 %N 2 %P 319-324 %@ 0194-911X %X Gene expression differences accompany both the onset and established phases of hypertension. By an integrated genome-transcriptome approach we performed a meta-analysis of data from 74 microarray experiments available on public databases to identify genes with altered expression in the kidney, adrenal, heart, and artery of spontaneously hypertensive and Lyon hypertensive rats. To identify genes responsible for the onset of hypertension we used a statistical approach that sought to eliminate expression differences that occur during maturation unrelated to hypertension. Based on this adjusted fold-difference statistic, we found 36 genes for which the expression differed between the prehypertensive phase and established hypertension. Genes having possible relevance to hypertension onset included Actn2, Ankrd1, ApoE, Cd36, Csrp3, Me1, Myl3, Nppa, Nppb, Pln, Postn, Spp1, Slc21a4, Slc22a2, Thbs4, and Tnni3. In established hypertension 102 genes exhibited altered expression after Bonferroni correction (P<0.05). These included Atp5o, Ech1, Fabp3, Gnb3, Ldhb, Myh6, Lpl, Pkkaca, Vegfb, Vcam1, and reduced nicotinamide-adenine dinucleotide dehydrogenases. Among the genes identified, there was an overrepresentation of gene ontology terms involved in energy production, fatty acid and lipid metabolism, oxidation, and transport. These could contribute to increases in reactive oxygen species. Our meta-analysis has revealed many new genes for which the expression is altered in hypertension, so pointing to novel potential causative, maintenance, and responsive mechanisms and pathways. %Z FOR Codes: 60408 10401 110201 %0 Journal Article %~ PubMed %A Morris, Brian J %T Sympathetic meta-analysis of adrenoceptor gene variants in hypertension. %B American Journal of Hypertension %D 2010 %C United States %I Nature Publishing Group %V 23 %N 3 %P 225 %@ 0895-7061 %X %Z FOR Codes: 110201 60499 110311 %0 Journal Article %~ PubMed %A Cooper, David A %A Wodak, Alex D %A Morris, Brian J %T The case for boosting infant male circumcision in the face of rising heterosexual transmission of HIV. %B The Medical Journal of Australia %D 2010 %C Australia %I Australasian Medical Publishing Company Pty. Ltd. %V 193 %N 6 %P 318-319 %@ 0025-729X %X Circumcision now to prevent heterosexual HIV transmission in 2030??makes sense. %Z FOR Codes: 111716 111403 110804 %0 Journal Article %~ PubMed %A Marques, Francine Z %A Markus, M Andrea %A Morris, Brian J %T The molecular basis of longevity, and clinical implications. %B Maturitas %D 2010 %C Ireland, Denmark %I Elsevier Ireland Ltd %V 65 %N 2 %P 87-91 %@ 1873-4111 %X The determinants of length of life are multifactorial and involve complex processes, most of which are not as yet understood completely. Tremendous advances have, however, been made in recent times in understanding some of the key molecular mechanisms that influence ageing and lifespan. Herein we highlight many of the more important findings and their potential clinical implications. Most of the intracellular factors involved in the ageing process, such as members of the sirtuin family, as well as insulin and insulin-like growth factor-I and their genes, are part of interconnected pathways. The manipulation of these and other genes in animal models can increase or decrease lifespan. Transcriptional and post-transcriptional regulatory mechanisms, some of which involve microRNAs, as well as modifications to chromatin and histones, can influence longevity. A decline in the function of stem cells might also be responsible for some aspects of mammalian ageing. Calorie restriction, polyphenols such as resveratrol, rapamycin, spermidine and angiotensin I converting enzyme inhibitor, are able to increase lifespan by modulation of branches of the longevity pathways. Molecular genetic studies of long-lived subjects have identified several potential candidate genes, but genetic research on ageing is in its infancy. Large genome-wide association studies should provide insights. Although new biomarkers for ageing and health, such as ones that might reveal telomere dysfunction, have been described, advances in the genetics and molecular biology of longevity will require interdisciplinary approaches if the much-hoped for success in alleviating the diseases of ageing, and an extension of both lifespan and healthspan is to be achieved. %Z FOR Codes: 60104 110199 110299 %0 Journal Article %~ PubMed %A Waskett, J H %A Morris, B J %A Weiss, H A %T Errors in meta-analysis by Van Howe. %B International Journal of STD & AIDS %D 2009 %C United States %I Wiley-Liss %V 20 %N 3 %P 216-218; author reply 218-20 %@ 0956-4624 %X %Z FOR Codes: 110309 %0 Journal Article %~ PubMed %A Morris, Brian J %T GRK4 genetics and response to beta-blocker. %B American Journal of Hypertension %D 2009 %C United States %I Nature Publishing Group %V 22 %N 3 %P 235-236 %@ 1879-1905 %X %Z FOR Codes: 110299 %0 Journal Article %~ PubMed %A Morris, Brian J %A Bailis, Stefan A %A Waskett, Jake H %A Wiswell, Thomas E %A Halperin, Daniel T %T Medicaid coverage of newborn circumcision: a health parity right of the poor. %B American Journal of Public Health %D 2009 %C United States %I American Public Health Association %V 99 %N 6 %P 969-971 %@ 1541-0048 %X %Z FOR Codes: 111799 %0 Journal Article %~ PubMed %A Morris, Brian J %T Might a leptin gene variant affect blood pressure in obese brazilians? %B American Journal of Hypertension %D 2009 %C United States %I Nature Publishing Group %V 22 %N 5 %P 467 %@ 1879-1905 %X %Z FOR Codes: 110299 %0 Journal Article %~ PubMed %A Markus, M Andrea %A Morris, Brian J %T RBM4: A multifunctional RNA-binding protein. %B The International Journal of Biochemistry & Cell Biology %D 2009 %C United Kingdom %I Pergamon %V 41 %N 4 %P 740-743 %@ 1357-2725 %X RBM4, also known as Lark, was described initially as having a role in circadian rhythm control in Drosophila. In the last 5 years data have emerged from studies of mammalian cells. It is now clear that RBM4 is an RNA-binding protein involved in diverse cellular processes that include alternative splicing of pre-mRNA, translation, and RNA silencing. Its structure, similar to other RNA-binding proteins, contains two RNA recognition motifs and a CCHC-type zinc finger. Here we review current information about the function of RBM4 and its localization within the cell. We then speculate about its possible relationship to disease. %Z FOR Codes: 110106 %0 Journal Article %~ PubMed %A Marques, Francine Z %A Markus, M Andrea %A Morris, Brian J %T Resveratrol: Cellular actions of a potent natural chemical that confers a diversity of health benefits. %B The International Journal of Biochemistry & Cell Biology %D 2009 %C United Kingdom %I Pergamon %V 41 %N 11 %P 2125-2128 %@ 1357-2725 %X Resveratrol is a polyphenolic flavonoid with potent antioxidant activity. It is found in a diversity of plants, notably berry fruit, and is attracting increased attention due to its health benefits, especially in common age-related diseases such as cancer, type 2 diabetes, cardiovascular disease, and neurological conditions. Resveratrol has positive effects on metabolism and can increase the lifespan of various organisms. Its effects arise from its capacity to interact with multiple molecular targets involved in diverse intracellular pathways. Most well known is the ability of resveratrol to activate sirtuins, a class of NAD(+)-dependent deacetylases that affect multiple transcription factors and other protein targets. More potent sirtuin activators have now been discovered by large-scale screening programs. Resveratrol and the new compounds are the subject of clinical trials to determine their consumer safety and suitability for the prevention and treatment of most common diseases of aging. %Z FOR Codes: 110199 111101 110499 %0 Journal Article %~ PubMed %A Loughlin, Fionna E %A Mansfield, Robyn E %A Vaz, Paula M %A McGrath, Aaron P %A Setiyaputra, Surya %A Gamsjaeger, Roland %A Chen, Eva S %A Morris, Brian J %A Guss, J Mitchell %A Mackay, Joel P %T The zinc fingers of the SR-like protein ZRANB2 are single-stranded RNA-binding domains that recognize 5' splice site-like sequences. %B Proceedings of the National Academy of Sciences of the United States of America %D 2009 %C United States %I Natl Acad Sciences %V 106 %N 14 %P 5581-5586 %@ 1091-6490 %X The alternative splicing of mRNA is a critical process in higher eukaryotes that generates substantial proteomic diversity. Many of the proteins that are essential to this process contain arginine/serine-rich (RS) domains. ZRANB2 is a widely-expressed and highly-conserved RS-domain protein that can regulate alternative splicing but lacks canonical RNA-binding domains. Instead, it contains 2 RanBP2-type zinc finger (ZnF) domains. We demonstrate that these ZnFs recognize ssRNA with high affinity and specificity. Each ZnF binds to a single AGGUAA motif and the 2 domains combine to recognize AGGUAA(N(x))AGGUAA double sites, suggesting that ZRANB2 regulates alternative splicing via a direct interaction with pre-mRNA at sites that resemble the consensus 5'' splice site. We show using X-ray crystallography that recognition of an AGGUAA motif by a single ZnF is dominated by side-chain hydrogen bonds to the bases and formation of a guanine-tryptophan-guanine "ladder." A number of other human proteins that function in RNA processing also contain RanBP2 ZnFs in which the RNA-binding residues of ZRANB2 are conserved. The ZnFs of ZRANB2 therefore define another class of RNA-binding domain, advancing our understanding of RNA recognition and emphasizing the versatility of ZnF domains in molecular recognition. %Z FOR Codes: 601 %0 Journal Article %~ PubMed %A Pönighaus, Claudia %A Speirs, Helen J L %A Morris, Brian J %A Kuhn, Joachim %A Kleesiek, Knut %A Götting, Christian %T Xylosyltransferase gene variants and their role in essential hypertension. %B American Journal of Hypertension %D 2009 %C United States %I Nature Publishing Group %V 22 %N 4 %P 432-436 %@ 1879-1905 %X BACKGROUND: An accumulation of extracellular matrix molecules, such as proteoglycans, is observed in the vascular wall of hypertensive patients. Xylosyltransferases I and II (XT-I and XT-II), the chain-initiating enzymes in the biosynthesis of proteoglycans, catalyze the transfer of D-xylose from UDP-D-xylose to specific serine residues of the core protein. Because associations between XYLT polymorphisms and an altered blood pressure have been observed, genetic variations in the XYLT genes might predispose to essential hypertension. The localization of the XYLT2 gene on chromosome 17q increases its attractiveness as this region has been reported to be a potential candidate locus for essential hypertension. METHODS: Genotyping of four polymorphisms in the genes XYLT1 and XYLT2 was performed in 150 unrelated essential hypertension patients and 150 age- and sex-matched normotensive controls using restriction fragment length polymorphism analysis. RESULTS: The allele and genotype frequencies of the XYLT variants investigated did not show any significant differences between patients and controls, among allele-carriers and nonallele-carriers and among recessive and nonrecessive allele-carriers comparing patients and controls. Systolic and diastolic blood pressures did not differ significantly between the genotypes concerning all XYLT variants analyzed. Two XYLT2 variants deviated from Hardy-Weinberg equilibrium (HWE) in the hypertensive group. CONCLUSIONS: No statistically significant association was found between four XYLT variants and hypertension or blood pressure, suggesting that they do not play a significant role in the development of essential hypertension. The deviation from HWE of two XYLT2 variants might be due to gene-phenotype associations which remain to be explored, as well as the possibility of gene-gene interactions. %Z FOR Codes: 110299 %0 Journal Article %A Morris, Brian %A Halperin, Daniel T. %A Klausner, Jeff D. %T Cut! %B New Scientist %D 2008 %C Australia %I Reed Business Information Pty Ltd. %V 2670 %N %P 20-21 %@ 1032-1233 %X %Z FOR Codes: 1116 %0 Journal Article %~ PubMed %A Martin, Sally %A Markus, M Andrea %A Morris, Brian J %A Davisson, Robin L %A Lawrence, Andrew J %A van den Buuse, Maarten %T Does angiotensin interact with dopaminergic mechanisms in the brain to modulate prepulse inhibition in mice? %B Neuropharmacology %D 2008 %C United Kingdom %I Pergamon %V 54 %N 2 %P 399-404 %@ 0028-3908 %X Changes in the levels of angiotensin-converting enzyme (ACE) have been found in brains of schizophrenia patients, suggesting a possible involvement of angiotensin in the illness. Prepulse inhibition (PPI) is a measure of sensorimotor gating and is disrupted in patients with schizophrenia. In a previous study, a reduction of ACE activity, either in ACE knockout mice or after ACE inhibitor treatment, markedly inhibited the disruption of PPI caused by the dopamine receptor agonist, apomorphine. ACE is not specific for the angiotensin system and, therefore, in the present study we assessed pharmacological regulation of PPI in two other, more specific genetic mouse models of altered angiotensin activity. We used renin-enhancer knockout (REKO) mice, which display reduced renin activity, and neuron-specific enolase (NSE)-AT1A mice, which selectively over-express angiotensin AT1A receptors in the brain. Treatment of these mice with apomorphine, the dopamine releaser, amphetamine or the NMDA receptor antagonist, MK-801, significantly disrupted PPI. There was, however, no difference in these effects between the genotypes. These data suggest that genetically induced changes in the activity of the angiotensin system do not alter regulation of PPI in mice. Our previous results on the effects of reduced ACE activity could be explained by mechanisms other than angiotensin, such as effects on enkephalin or bradykinin metabolism. %Z FOR Codes: 110999 %0 Journal Article %~ PubMed %A Morris, Brian J %T Fluorescence activated cell sorting of transiently transfected As4.1 cells shows renin enhancer directs on/off switching of renin promoter in vitro. %B Clinical and Experimental Pharmacology & Physiology %D 2008 %C Australia %I Blackwell Publishing Asia %V 35 %N 4 %P 367-371 %@ 1440-1681 %X 1. The proximal promoter of the renin gene is weak and its activity is influenced by a strong, far-upstream enhancer. This and the ability of renin expression in renal afferent arteriolar cells to be ''recruited'' under chronic stimulation is consistent with the on/off switching (variegation) model of gene expression. If true, this would provide an example in which variegation controls a physiologically regulable gene. 2. The present study tested the hypothesis that renin promoter activity may accord with the variegation model, at least in individual juxtaglomerular (mouse As4.1) cells in vitro. 3. As4.1 cells were transiently transfected with constructs containing the mouse renin (Ren-1c) enhancer adjacent to the Ren-1c promoter and a linked reporter gene encoding enhanced green fluorescent protein (EGFP). The EGFP signal from individual cells was monitored by fluorescence activated cell sorting. 4. In the presence of the renin enhancer there was 10-fold higher EGFP expression in transfected cells compared with cells transfected with EGFP constructs containing the promoter alone. There was, moreover, an 8-fold increase in the number of EGFP expressing cells. However, EGFP expression in individual transfected cells was similar in the presence or absence of the enhancer. 5. Results from the in vitro system used suggest that the Ren-1c enhancer does not regulate the rate of promoter activity, but rather increases the probability of achieving an active transcriptional state. Limitations of these findings are discussed. %Z FOR Codes: 110105 110201 %0 Book Section %A Morris, Brian %T How Xenohormetic Compounds Confer Health Benefits %B Mild Stress and Healthy Aging %D 2008 %C Netherlands %I Springer Science+Business Media %V %N %P 115-138 %@ 978-1-4020-6868-3 %E Le Bourg, Eric %E Rattan, Suresh I.S. %X %Z FOR Codes: 111601 110308 %0 Journal Article %A Halperin, Daniel T %A Wamai, Richard G %A Weiss, Helen A %A Hankins, Catherine %A Agot, Kawango %A Abdool Karim, Quarraisha %A Shisana, Olive %A Bailey, Robert C %A Betukumesu, Bilonda %A Bongaarts, John %A Bowa, Kasonde %A Cash, Richard %A al, et %A Morris, Brian %T Male circumcision is an efficacious, lasting and cost-effective strategy for combating HIV in high-prevalence AIDS epidemics %B Future HIV Therapy %D 2008 %C United Kingdom %I Future Medicine Ltd. %V 2 %N %P 399-405 %@ 1758-4310 %X %Z FOR Codes: 110309 %0 Book Section %A Abete, Pasquale %A Calabrese, Edward J. %A Ji, Li Li %A Kristensen, Torsten %A Le Bourg, Eric %A Loeschcke, Volker %A Morris, Brian %A Rengo,, Franco %A Rattan, Suresh I. S. %A Safwat, Akmal %A Sarup, Pernille %A Sørensen, Jesper %A Vaiserman, Alexander %T Mild Stress and Healthy Aging: Perspectives for Human Beings %B Mild Stress and Healthy Aging %D 2008 %C Netherlands %I Springer Science+Business Media %V %N %P 171-183 %@ 978-1-4020-6868-3 %E Le Bourg, Eric %E Rattan, Suresh I.S. %X %Z FOR Codes: 111601 110308 %0 Journal Article %~ PubMed %A Waskett, J H %A Morris, B J %T Re: 'RS Van Howe, FM Hodges. The carcinogenicity of smegma: debunking a myth.' An example of myth and mythchief making? %B Journal of the European Academy of Dermatology and Venereology %D 2008 %C UK, Belgium. %I Wiley- Blackwell Publishing Ltd. %V 22 %N 1 %P 131 %@ 0926-9959 %X %Z FOR Codes: 110304 110324 %0 Journal Article %~ PubMed %A Markus, M Andrea %A Morris, Brian J %T Resveratrol in prevention and treatment of common clinical conditions of aging. %B Clinical Interventions in Aging %D 2008 %C New Zealand %I Dove Medical Press Ltd %V 3 %N 2 %P 331-339 %@ 1176-9092 %X Resveratrol is a potent member of the class of natural, plant-derived chemicals known as polyphenols. These help explain in part why a diet high in fruit and vegetables confers health benefits and are associated with reduced risk of common complex conditions such as cardiovascular disease, cancer, diabetes, and Alzheimer''s disease. We present the latest molecular findings that account for the beneficial actions of resveratrol. The intracellular pathways activated are crucial for anti-oxidant defence, regulation of the cell cycle, mitochondrial energy production, vascular tone, oncogene suppression, and many other phenomena which if unchecked lead to morbidity and mortality from onset and progression of these various diseases. While a healthy diet and lifestyle is strongly recommended in prevention of such conditions, the future bodes well for the use of resveratrol and analogues of higher potency than the natural form for treatment of diseases that afflict humans, particularly as they age. %Z FOR Codes: 110399 %0 Journal Article %~ PubMed %A Morris, Brian J %A Waskett, Jake %A Bailis, Stefan A %T Case number and the financial impact of circumcision in reducing prostate cancer. %B BJU International %D 2007 %C Australia, UK. %I Biomed Central Ltd. %V 100 %N 1 %P 5-6 %@ 1464-4096 %X %Z FOR Codes: 111706 110309 %0 Journal Article %~ PubMed %A Morris, Brian J %A Rose, Barbara R %T Cervical screening in the 21st century: the case for human papillomavirus testing of self-collected specimens. %B Clinical Chemistry and Laboratory Medicine %D 2007 %C Germany %I Walter De Gruyter GmbH & Co. KG %V 45 %N 5 %P 577-591 %@ 1434-6621 %X Cervical screening by Pap smear involves a high rate of false negatives, necessitating frequent testing. Because women do not like the sampling procedure, many avoid being screened. Testing for the causative high-risk human papillomavirus (HPV) types, by PCR or other technologies, on self-collected (tampon) samples permits women to be monitored non-invasively. The high negative predictive value of HPV testing means a greater interval between tests, and thus reduces costs. HPV testing lends itself to primary screening. A kit for self-collection and return to a testing laboratory, followed by practitioner notification and follow-up if required, should result in wider participation. The higher accuracy of HPV testing should lead to improved cervical cancer prevention. %Z FOR Codes: 111717 110804 110105 %0 Journal Article %~ PubMed %A Morris, Brian J %T Circumcision in Australia: prevalence and effects on sexual health. %B International Journal of STD & AIDS %D 2007 %C UK %I Royal Society of Medicine Press Ltd %V 18 %N 1 %P 69-70 %@ 0956-4624 %X %Z FOR Codes: 111706 110312 110802 %0 Journal Article %~ PubMed %A Morris, Brian J %T Climate not cultivars in the NO-ing of red wines. %B Journal of Hypertension %D 2007 %C United Kingdom, US. %I Lippincott Williams & Wilkins %V 25 %N 3 %P 501-503 %@ 0263-6352 %X %Z FOR Codes: 111101 110302 111601 %0 Journal Article %~ PubMed %A Waskett, Jake H %A Morris, Brian J %T Fine-touch pressure thresholds in the adult penis. %B BJU International %D 2007 %C UK, Australia. %I Blackwell Publishing Ltd. %V 99 %N 6 %P 1551-1552 %@ 1464-4096 %X %Z FOR Codes: 110905 111706 110312 %0 Journal Article %~ PubMed %A Yang, Zhiyong %A Venardos, Kylie %A Jones, Emma %A Morris, Brian J %A Chin-Dusting, Jaye %A Kaye, David M %T Identification of a novel polymorphism in the 3'UTR of the L-arginine transporter gene SLC7A1: contribution to hypertension and endothelial dysfunction. %B Circulation %D 2007 %C US %I Lippincott Williams & Wilkins %V 115 %N 10 %P 1269-1274 %@ 1524-4539 %X BACKGROUND: Endothelial dysfunction because of reduced nitric oxide bioavailability is a key feature of essential hypertension. We have found that normotensive siblings of subjects with essential hypertension have impaired endothelial function accompanied by altered arginine metabolism. METHODS AND RESULTS: We have identified a novel C/T polymorphism in the 3''UTR of the principal arginine transporter, solute carrier family 7 (cationic amino acid transporter, y+ system), member 1 gene (SLC7A1). The minor T allele significantly attenuates reporter gene expression (P<0.01) and is impaired in its capacity to form DNA-protein complexes (P<0.05). In 278 hypertensive subjects the frequency of the T allele was 13.3% compared with 7.6% in 498 normotensive subjects (P<0.001). Moreover, the overall genotype distribution observed in hypertensives differed significantly from that in normotensives (P<0.001). To complement these studies, we generated an endothelial-specific transgenic mouse overexpressing L-arginine transporter SLC7A1. The Slc7A1 transgenic mice exhibited significantly enhanced responses to the endothelium-dependent vasodilator acetylcholine (-log EC50 for wild-type versus Slc7A1 transgenic: 6.87+/-0.10 versus 7.56+/-0.13; P<0.001). This was accompanied by elevated production of nitric oxide by isolated aortic endothelial cells. CONCLUSIONS: The present study identifies a key, functionally active polymorphism in the 3''UTR of SLC7A1. As such, this polymorphism may account for the apparent link between altered endothelial function, L-arginine, and nitric oxide metabolism and predisposition to essential hypertension. %Z FOR Codes: 110105 110311 %0 Journal Article %~ PubMed %A Jackson, Kristy %A Head, Geoffrey A %A Morris, Brian J %A Chin-Dusting, Jaye %A Jones, Emma %A La Greca, Luisa %A Mayorov, Dmitry N %T Reduced cardiovascular reactivity to stress but not feeding in renin enhancer knockout mice. %B American Journal of Hypertension %D 2007 %C United States %I Nature Publishing Group %V 20 %N 8 %P 893-899 %@ 0895-7061 %X BACKGROUND: We have recently shown that the renin enhancer, a regulatory element of renin gene transcription, is important in the long-term control of basal blood pressure (BP). In this study, we examined whether the renin enhancer deficit alters the acute pressor response to emotional stress in mice. METHODS: Under fluothane anesthesia, wild-type (C57BL6, n=7) and the Ren-1c enhancer knockout (REKO, n=8) mice were implanted with telemetry devices to measure BP and locomotor activity. RESULTS: Resting BP in REKO mice (94+/-3 mm Hg) was lower than in wild-type mice (102+/-2 mm Hg). Shaker stress elicited prompt pressor (+25+/-2 mm Hg), tachycardic (+145+/-25 beats/min), and locomotor responses in wild-type mice. The BP and locomotor responses were decreased in REKO mice by 39%+/-12% (P=.03) and 64%+/-11% (P=.02), respectively, whereas the tachycardic response remained unchanged. Restraint stress increased BP by 27+/-1 mm Hg in wild-type mice. The BP response was attenuated in REKO mice by 21%+/-8% (P=.05), and this attenuation could not be ascribed to reduced locomotor activity during stress. Cardiovascular arousal associated with presentation and eating palatable food was similar in wild-type (+19+/-2 mm Hg and +174+/-21 beats/min) and REKO (+19+/-2 mm Hg and +147+/-17 beats/min) mice. The contractile response to the alpha-adrenoceptor agonist phenylephrine was reduced in aortas from REKO mice, whereas that to angiotensin II was not different between strains. CONCLUSIONS: The disrupted regulation of renin synthesis caused by the renin enhancer deficit in mice is associated with a selective reduction in BP reactivity to aversive stress, which may be mediated by multiple central and peripheral mechanisms. %Z FOR Codes: 110903 111603 110105 %0 Journal Article %~ PubMed %A Markus, M Andrea %A Goy, Christine %A Adams, David J %A Lovicu, Frank J %A Morris, Brian J %T Renin Enhancer Is Crucial for Full Response in Renin Expression to an In Vivo Stimulus. %B Hypertension %D 2007 %C 530 WALNUT ST, PHILA %I Lippincott Williams & Wilkins %V 50 %N %P 933-8 %@ 1524-4563 %X We showed recently that deletion of a strong enhancer located 2.7 kb upstream of the renin gene in mice produces a strain with mild hypotension and salt-sensitivity. Here we set out to compare responses in renin expression in kidney and extrarenal tissues in these "REKO" mice. REKO and wild-type mice were placed on a low NaCl/enalapril regimen for 1 week, and then Ren-1(c) mRNA and renin enzyme activities were measured in tissues and plasma. In untreated REKO mice, renin and Ren-1(c) mRNA were reduced significantly in kidney, submandibular gland, adrenal, heart, and brain. In situ hybridization indicated a marked reduction in Ren-1(c) mRNA in juxtaglomerular cells and granular ducts of submandibular gland. After the chronic stimulus response in renal Ren-1(c) mRNA in REKO mice was blunted by 54% compared with wild-type mice, and was accompanied by almost complete exhaustion of renin stores. Response in plasma renin was blunted by 47%, this being mirrored in heart (54% decline), in which renin is derived mostly from the bloodstream. In adrenal a 55% reduction was seen. These data are consistent with inability of REKO mice to adequately replenish renal renin stores during chronic stimulation of renin secretion. In conclusion, the renin enhancer is critical for replenishment of renin stores and response in renin to a chronic in vivo stimulus. %Z FOR Codes: 110105 111699 %0 Journal Article %~ PubMed %A Stefani, Maurizio %A Markus, Marietta Andrea %A Lin, Ruby C Y %A Pinese, Mark %A Dawes, Ian A %A Morris, Brian James %T The Effect of Resveratrol on a Cell Model of Human Aging. %B Annals of the New York Academy of Sciences %D 2007 %C 2 East 63Rd St, New %I New York Acad Sciences %V 1114 %N %P 407-418 %@ 0077-8923 %X The natural polyphenol resveratrol stimulates sirtuins and extends lifespan. Here resveratrol inhibited expression of replicative senescence marker INK4a in human dermal fibroblasts, and 47 of 19,000 genes from microarray experiments were differentially expressed. These included genes for growth, cell division, cell signaling, apoptosis, and transcription. Genes involved in Ras and ubiquitin pathways, Ras-GRF1, RAC3, and UBE2D3, were downregulated. The changes suggest resveratrol might alter sirtuin-regulated downstream pathways, rather than sirtuin activity. Serum deprivation and high confluency caused nuclear translocation of the SIRT1-regulated transcription factor FOXO3a. Our data indicate resveratrol''s actions might cause FOXO recruitment to the nucleus. %Z FOR Codes: 110105 110403 %0 Journal Article %A Mangs, A Helena %A Morris, Brian %T The human pseudoautosomal region: origin, function and future. %B Current Genomics %D 2007 %C United States %I Bentham Science Publishers Ltd. %V 8 %N 0 %P 129-136 %@ 1389-2029 %X %Z FOR Codes: 60408 %0 Journal Article %~ PubMed %A Morris, Brian J %T Why circumcision is a biomedical imperative for the 21(st) century. %B BioEssays %D 2007 %C United Kingdom %I John Wiley & Sons Ltd. %V 29 %N 11 %P 1147-1158 %@ 0265-9247 %X Circumcision of males represents a surgical "vaccine" against a wide variety of infections, adverse medical conditions and potentially fatal diseases over their lifetime, and also protects their sexual partners. In experienced hands, this common, inexpensive procedure is very safe, can be pain-free and can be performed at any age. The benefits vastly outweigh risks. The enormous public health benefits include protection from urinary tract infections, sexually transmitted HIV, HPV, syphilis and chancroid, penile and prostate cancer, phimosis, thrush, and inflammatory dermatoses. In women circumcision of the male partner provides substantial protection from cervical cancer and chlamydia. Circumcision has socio-sexual benefits and reduces sexual problems with age. It has no adverse effect on penile sensitivity, function, or sensation during sexual arousal. Most women prefer the circumcised penis for appearance, hygiene and sex. Given the convincing epidemiological evidence and biological support, routine circumcision should be highly recommended by all health professionals. %Z FOR Codes: 110199 %0 Journal Article %~ PubMed %A Mangs, A Helena %A Morris, Brian J %T ZRANB2: Structural and functional insights into a novel splicing protein. %B The International Journal of Biochemistry & Cell Biology %D 2007 %C United Kingdom %I Pergamon %V 40 %N 0 %P 2353-2357 %@ 1357-2725 %X ZRANB2 was identified originally in a differential display experiment on 2-day and 10-day primary cultures of rat juxtaglomerular cells. During prolonged culture it was found to undergo down-regulation in concert with renin, the archetypical constituent of these cells. ZRANB2 has two zinc fingers that form a novel fold and show striking homology to Ran-binding protein domains. Human ZRANB2 mRNA is alternatively spliced to give two variants with different 3'' ends. ZRANB2 has homologues across a range of species, the N-terminal end being particularly conserved. ZRANB2 is present in the nucleus of human cells. It binds to mRNA, as well as the essential splicing factors U170K and U2AF35 and the novel splicing component SFRS17A (formerly known as XE7). ZRANB2 is one of 20 genes up-regulated in grade III ovarian serous papillary carcinoma. Here, we review current knowledge surrounding ZRANB2. %Z FOR Codes: 110105