Knowledge, attitudes, and practices related to breast cancer screening among female Jordanian university employees: A cross-sectional study.

INTRODUCTION: To improve participation in breast screening programs, the level of knowledge about BC, attitudes, and practices of women in different sections of society must be understood. This study aimed to measure the level of knowledge of BC risk factors, signs and symptoms and determine current mammography practices among female employees at Jordanian universities. METHODS: A cross-sectional descriptive study was conducted on female employees at Jordanian government universities. Data was collected using a structured questionnaire that included: sociodemographic characteristics, knowledge of BC risk factors, knowledge of BC symptoms and knowledge, attitude and practice of mammography as an early detection method. RESULTS: A total of 362 participants completed the questionnaire. Overall, 174 scored ≥50% correct answers regarding BC risk factors, while 231 scored ≥50% correct answers regarding BC signs and symptoms. Half of the participants (n = 184, 50.8%) understood mammography to be an early BC detection method. Among those participants, 95 (51.6%) were eligible for screening and 39 (21.2%) had had a previous mammogram. The main reason for not engaging in mammography was the absence of BC signs and symptoms (37.2%). Profession, educational level and family history of BC were associated with increased knowledge of BC risk factors, signs and symptoms (p = 0.01). Lecturers in medical faculties exhibited the highest level of knowledge about mammography compared to participants in other professions (p = 0.02). CONCLUSION: Only 79 participants had good to excellent knowledge about BC. Participants' profession was the major indicator for awareness of BC and mammography as an early detection method. IMPLICATIONS FOR PRACTICE: The findings of this study reinforce the importance of providing BC educational programs for university employees in Jordan to increase awareness of BC and mammography.

Integrated computational approaches assisted development of a novel multi-epitope vaccine against MDR Streptococcus pseudopneumoniae.

The emergence of antibiotic resistance (AR) in bacteria is becoming an alarming health concern because it allows them to adapt themselves to changing environments. It is possible to prevent the spread of AR in many ways, such as reducing antibiotic misuse in human and veterinary medicine. Streptococcus pseudopneumoniae is one of these AR bacterial species that can cause pneumonia in humans and is responsible for high mortality and morbidity rates. It is oval shaped gram-positive bacterium that shows resistance to several antibiotics like penicillin, tetracycline, ciprofloxacin, erythromycin, and co-trimoxazale and no approved vaccine is available to overcome diseases of the pathogen. Thus, substantial efforts are necessary to select protective antigens from a whole genome of pathogens that are easily tested experimentally. The in silico designed vaccine was safe and potent in immunizing individuals against the aforementioned pathogens. Herein, we utilized a subtractive genomic approach to identify potential epitope-based vaccine candidates against S. pseudopneumoniae. In total, 50850 proteins were retrieved from the NCBI, representing the complete genome of S. pseudopneumoniae. Out of the total, CD-HIT analysis identified 1022 proteins as non-redundant and 49828 proteins as redundant and further subjected for subcellular localization in which bulk of proteins was located in the cytoplasm, with seven extracellular proteins (penicillin-binding protein, alpha-amylase, solute-binding protein, hypothetical protein, CHAP domain-containing protein, polysaccharide deacetylase family protein, hypothetical protein). Six immune cells epitopes (SNLQSENDRL, RNDSLQKQAR, NPTTTSEGF, KVKKKNNKK, AYSQGSQKEH, and SVVDQVSGDF) were predicted with the help of the IEDB server. To design a multi-epitopes vaccine these immune cell epitopes were together by GPGPG and adjuvant linker to enhance immune response efficacy. The 3D structure of the designed vaccine was modeled and conducted molecular docking and dynamic simulation studies were to check the binding efficacy with immune cells receptor and dynamic behavior of the docked complex. Finally, we concluded that the designed vaccine construct can provoke a proper and protective immune response against S. pseudopneumoniae.

Relationship between MCP1 (-2518A>G) gene variants and ovarian cancer in Turkish population.

The monocyte chemoattractant protein-1 (MCP-1) gene polymorphism(-2518A>G)  in the regulatory region of the MCP-1 protein has been reported to be associated with cancer risk. In this study we aimed to investigate the relationship of MCP-1 (-2518A>G) gene polymorphism and ovarian cancer. MCP-1 genotyping was performed using polymerase chain reaction from blood samples ofovarian cancer patient (n=56) and a control groups (n=52).There was a significant difference in MCP1 (-2518A>G) genotypes between the patient and control groups (p=0.049; x2=6.042). AA carriers were significantly higher in the control group (p=0.014) whereas AG genotype and G allele carriers were significantly higher in the ovarian cancer group (p=0.029, p=0.014, respectively). This study suggests that MCP-1 (-2518A>G) AG genotype and G allele could be considered as risk factor for susceptibility to ovarian cancer.

Anti-leukemic activity and tolerability of anti-human CD47 monoclonal antibodies.

CD47, a broadly expressed cell surface protein, inhibits cell phagocytosis via interaction with phagocyte-expressed SIRPα. A variety of hematological malignancies demonstrate elevated CD47 expression, suggesting that CD47 may mediate immune escape. We discovered three unique CD47-SIRPα blocking anti-CD47 monoclonal antibodies (mAbs) with low nano-molar affinity to human and cynomolgus monkey CD47, and no hemagglutination and platelet aggregation activity. To characterize the anti-cancer activity elicited by blocking CD47, the mAbs were cloned into effector function silent and competent Fc backbones. Effector function competent mAbs demonstrated potent activity in vitro and in vivo, while effector function silent mAbs demonstrated minimal activity, indicating that blocking CD47 only leads to a therapeutic effect in the presence of Fc effector function. A non-human primate study revealed that the effector function competent mAb IgG1 C47B222-(CHO) decreased red blood cells (RBC), hematocrit and hemoglobin by >40% at 1 mg/kg, whereas the effector function silent mAb IgG2σ C47B222-(CHO) had minimal impact on RBC indices at 1 and 10 mg/kg. Taken together, our findings suggest that targeting CD47 is an attractive therapeutic anti-cancer approach. However, the anti-cancer activity observed with anti-CD47 mAbs is Fc effector dependent as are the side effects observed on RBC indices.

Targeting of BCR-ABL: Lessons learned from BCR-ABL inhibition.

In 1960 researchers reported that balanced translocation between chromosomes 22 and 9 resulted in the generation of Philadelphia chromosome. This breakthrough revolutionized our knowledge related to leukemia biology and contemporary studies revealed that chromosomal translocation resulted in the fusion between the 5' segment of BCR gene and 3' segment of the ABL gene to form BCR/ABL fusion gene. Research over the years has progressively and systematically improved our understanding of the genetic and proteomic basis of Leukemia. Genome-wide profiling studies, including genome sequencing and microarray analysis, have helped us in identification of different intracellular signaling cascades that are frequently mutated in Leukemia.  We partition this multi-component review into different sections related to biochemical characteristics of BCR-ABL+ cells, underlying mechanism of generation of mutations and crosstalk of BCR-ABL with various intracellular signaling cascades. We also summarize how BCR-ABL encoding mRNA is negatively regulated by different miRNAs and the strategies which are currently being used to effectively target BCR-ABL protein. We also provide an overview of the natural products which have been used for targeting of BCR-ABL protein. Better understanding of the protein network of Philadelphia positive leukemic cells will prove to be helpful in getting a step closer to personalized medicine.

How sesquiterpenes modulate signaling cascades in cancers.

Data obtained from high-throughput technologies has started to shed light on the interplay between signal transduction cascades and chromatin modifications thus adding another layer of complexity to the already complex regulation of the protein network. Based on the insights gleaned from almost a decade of research, it has now been convincingly revealed that sesquiterpenes effectively modulated different intracellular signaling cascades in different cancers. In this review we summarize how sesquiterpenes mediated Wnt, Shh, Notch and TRAIL induced signaling cascades.

Tudor tells about new twists in the story tale of SMURFs.

Smad ubiquitin regulatory factors (SMURFS) belong to the HECT- family of E3 ubiquitin ligases. This family has two members, SMURF1 and SMURF2. SMURFs have emerged as well studied negative regulators of TGF induced intracellular signaling. However, increasingly it is being realized that SMURFs tactfully modulate an array of proteins in different cancers. This review sets spotlight on how SMURF1 and SMURF2 communicate with effectors of different signaling pathways during the multistep progression to cancer. We also summarize how microRNAs (miRNAs) effectively control SMURFs in different cancers. Role of SMURFs is context dependent in different cancers and better concepts related to miRNA regulation of SMURFs in different stages and steps of cancer will be helpful in efficient translation of laboratory findings to clinic.

The effects of melatonin on endometriotic lesions induced by implanting human endometriotic cells in the first SCID-mouse endometriosis-model developed in Turkey.

OBJECTIVE: To evaluate the effects of melatonin on endometriotic lesions induced by implanting human endometriotic cells in SCID mice. MATERIALS AND METHODS: Prospective, randomized, controlled, experimental study. Experimental Research Center of Yeditepe University (YUDETAM). Thirty female, non-pregnant, nulligravid severe combined immunodeficient (SCID) mice. Endometriotic cells collected from patients with endometriosis were implanted subcutaneously in 30 SCID mice. These mice were randomized into two study groups: in the first group, mice were administered melatonin (20 mg/kg/day) following induction of endometriosis for four weeks; in the second group, nothing was administered. All the mice were given a high dose of exogenous estradiol (50 µg/kg/d, twice weekly). Four weeks after inoculation, necropsies were performed and endometriotic lesions were collected. All the lesions were evaluated histopathologically and the levels of SOD and MDA were assessed in the lesions. RESULTS: Successful implantation was observed in the 28 mice that survived. Mean MDA level was 5.0 ± 1.7 and 8.8 ± 2.6 in the melatonin and control groups, respectively (p = 0.01); mean SOD level was 1.1 ± 0.1 and 1.0 ± 0.1 in the melatonin and control groups, respectively (p = 0.49). Mean histopathological score was lower in the melatonin group (p = 0.04). CONCLUSIONS: Melatonin was effective in the treatment of experimental endometriosis induced in SCID mice.

Signaling lansdscape of prostate cancer.

Research over the decades has gradually and sequentially shown that both intratumor heterogeneity and multifocality make prostate cancer difficult to target. Different challenges associated with generation of risk-stratification tools that correlate genomic landscape with clinical outcomes severely influence clinical efficacy of therapeutic strategies. Androgen receptor mediated signaling has gained great appreciation and rewiring of AR induced signaling cascade in absence of androgen, structural variants of AR have provided near complete resolution of genomic landscape and underlying mechanisms of prostate cancer. In this review we have attempted to provide an overview of most recent advancements in our knowledge related to different signaling cascades including TGF, SHH, Notch, JAK-STAT in prostate cancer progression and development.

VEGF mediated signaling in oral cancer.

Increasingly it is being realized that oral cancer arises from genetic/epigenetic mutations, dysregulations of spatio-temporally controlled signal transduction cascades and loss of apoptosis. Epidemiological studies have provided a stronger association between tobacco use (chewed and smoked) and oral cancer. Nevertheless, alcohol has also gained attention as a significant risk factor, having a multiplicative synergistic cancer promoting effect with tobacco. Vascular Endothelial Growth Factor (VEGF) mediated signaling has gained limelight because of its instrumental role in endothelial cell proliferation, survival, invasion, migration, chemotaxis of bone marrow (BM)-derived progenitor cells, vasodilation and vascular permeability. In this review we provide most recent updates on involvement of VEGF/VEGFR signaling axis in oral cancer. We partition this multi-component review into different sections and summarize latest advancements related to therapies against VEGF/VEGFR signaling axis and how microRNAs tactfully modulate VEGF and VEGFR in oral cancers. Data obtained through preclinical and clinical studies has revealed that therapeutic benefits associated with VEGF-targeted therapy are complicated in different cancers and involve myriad of mechanisms. A better understanding of VEGF/VEGFR mediated signaling in oral cancers and testing of novel therapeutic agents in preclinical models will prove to be helpful in effective translation of safest drugs from benchtop to the bedside.

Effects of aloe vera gel on the induction of endometriosis and regression of endometrial explants in a rat model.

PURPOSE OF INVESTIGATION: To evaluate the preventive and reducing effect of aloe vera gel on surgically-induced endometrial foci in rats. MATERIALS AND METHODS: Twenty-four reproductive aged female non-pregnant, nulligravid Sprague-Dawley albino rats were used. The rats were randomly divided to three groups (Group 1: control, Group 2: aloe vera endometriosis formation, and Group 3: aloe vera endometriosis treatment). A peritoneal lavage using one-ml saline was taken at all the operations for determination of superoxide dismutase (SOD), malondialdehyde (MDA), and catalase (CAT). Forty-eight horns were implanted in 24 rats. RESULTS: All the implants were properly formed after implantation. In Group 3, before aloe vera application, the sum of the volumes was 87.2 ± 20.4 mm³ and after treatment the volumes dropped to 28.9 ± 14.9 mm3 (p = 0.01). As evaluation of aloe vera on the formation of endometriosis in the second operation in Group 2, the sum of the volumes was 2.9±1.4 mm³ and in Group 1, 118.9 ± 20.0 mm3 (p = 0.001). Likewise, similar changes were observed in the histopatological scores. CONCLUSION: The application of aloe vera was seen to raise antioxidant levels in the peritoneal fluid and to reduce oxidative stress markers. Aloe vera is effective in the inhibition of formation and regression of endometriotic lesions.

Natural products are the future of anticancer therapy: Preclinical and clinical advancements of Viscum album phytometabolites.

Cancer is a multifaceted and genomically complex disease. Research over the years has gradually provided a near complete resolution of cancer landscape and it is now known that genetic/epigenetic mutations, inactivation of tumor suppressors, Overexpression of oncogenes, spatio-temporally dysregulated intracellular signaling cascades, epithelial to mesenchymal transition (EMT), metastasis and loss of apoptosis are some of the most extensively studied biological mechanisms that underpin cancer development and progression. Increasingly it is being realized that current therapeutic interventions are becoming ineffective because of tumor heterogeneity and rapidly developing resistance against drugs. Considerable biological activities exerted by bioactive ingredients isolated from natural sources have revolutionized the field of natural product chemistry and rapid developments in preclinical studies are encouraging. Viscum album has emerged as a deeply studied natural source with substantial and multifaceted biological activities. In this review we have attempted to provide recent breakthroughs in existing scientific literature with emphasis on targeting of protein network in cancer cells. We partition this review into different sections, highlighting latest information from cell culture studies, preclinical and clinically oriented studies. We summarized how bioactive ingredients of Viscum album modulated extrinsic and intrinsic pathways in cancer cells. However, surprisingly, none of the study reported stimulatory effects on TRAIL receptors. The review provided in-depth analysis of how Viscum album modulated Endoplasmic Reticulum Stress in cancer cells and how bioactive chemicals tactfully targeted cytoskeletal machinery in cancer cells as evidenced by cell culture studies. It is noteworthy that Viscum album has entered into various phases of clinical trials, however, there are still knowledge gaps in our understanding regarding how various bioactive constituents of Viscum album modulate intracellular signaling cascades in cancer. Better and deeper comprehension oncogenic signaling cascades will prove to be helful in getting a step closer to individualized medicine.

Comparative efficacy of active and passive distraction during restorative treatment in children using an iPad versus audiovisual eyeglasses: a randomised controlled trial.

AIM: This study aimed to compare the effects of two types of distraction techniques: passive, using audiovisual glasses (AV glasses), versus active, using an iPad, as an adjunct to local analgesia during vital pulp therapy in children. METHODS: Pain behaviour, and heart rates from an exposure group (treatment with the aid of an iPad) and control group (treatment with the aid of AV glasses) were compared in a randomised, split-mouth design using the Wilcoxon signed rank test (pain and behaviour) and paired t test for heart rate scores at p 0.05. RESULTS: Children (39) (mean age 6.27 years) received the two treatment sessions. Generally, AV glasses had higher pain and behaviour scores than iPad. Pain results demonstrated marginal significant differences between the two distraction techniques during local analgesia administration (p 0.076) and caries removal (p 0.071). A significant difference between the two techniques during local analgesia administration only (p 0.017), in favour of an iPad. Average heart rates over the treatment intervals were lower among iPad group than those using AV glasses group. Patients preferred an iPad more than AV glasses (24 versus 15). Treatment sessions were significantly shorter for iPad. CONCLUSIONS: Active distraction using an iPad demonstrated better performance than passive distraction using AV glasses.

Differential response of head and neck cancer cell lines to TRAIL or Smac mimetics is associated with the cellular levels and activity of caspase-8 and caspase-10.

BACKGROUND: Current treatment strategies for head and neck cancer are associated with significant morbidity and up to 50% of patients relapse, highlighting the need for more specific and effective therapeutics. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and Smac mimetics (SMs) are promising anticancer agents, but their effect on head and neck squamous cell carcinoma (HNSCC) remains unknown. METHODS: We examined the response of a panel of nine HNSCC cell lines to TRAIL and SMs and investigated the mechanism of cell type-specific response by functional analysis. RESULTS: Head and neck cancer cell lines revealed a converse response pattern with three cell lines being highly sensitive to Smac-164 (SM) but resistant to TRAIL, whereas the other six were sensitive to TRAIL but resistant to SM. Distinct protein expression and activation patterns were found to be associated with susceptibility of HNSCC cell lines to TRAIL and SM. Tumour necrosis factor-related apoptosis-inducing ligand sensitivity was associated with high caspase-8 and Bid protein levels, and TRAIL-sensitive cell lines were killed via the type II extrinsic apoptotic pathway. Smac mimetic-sensitive cells expressed low levels of caspase-8 and Bid but had high TNF-α expression. Smac mimetic-induced cell death was associated with caspase-10 activation, suggesting that in the absence of caspase-8, caspase-10 mediates response to SM. Cotreatment with TNF-α sensitised the resistant cells to SM, demonstrating a decisive role for TNF-α-driven feedback loop in SM sensitivity. CONCLUSIONS: Tumour necrosis factor-related apoptosis-inducing ligand and SMs effectively kill HNSCC cell lines and therefore represent potential targeted therapeutics for head and neck cancer. Distinct molecular mechanisms determine the sensitivity to each agent, with levels of TNF-α, caspase-8, Bid and caspase-10 providing important predictive biomarkers of response to these agents.

Comparision of reproductive outcome of the women with hypogonadotropic hypogonadism and tubal factor infertility.

OBJECTIVE: To evaluate the outcome of women with hypogonadotropic hypogonadism (HH) undergoing in-vitro fertilization (IVF). MATERIALS AND METHODS: Data from 13 cycles often hypogonadotropic patients treated with in vitro fertilization from the period January 2006 to January 2008 were analyzed and compared with treatment results from 20 patients with tubal factor infertility (TI). All patients underwent ovarian hyperstimulation for IVF/ICSI at the same center. HH patients initiated the treatment by receiving daily injections of hMG. The patients in the control group were given the same dosage of recombinant FSH. RESULTS: Demographic characteristics of the patients were comparable. Mean duration of stimulation was 13 days in the HH group and nine days in the TI group; the difference was significant (p < 0.001). Significantly more gonadotropins were used for the stimulation of HH patients (p < 0.05). Peak serum E2 concentration was found to be higher in the TI group. We evaluated the proportion of metaphase II (MII) oocytes to total oocytes retrieved in HH patients and found the number was similar to the TI group. Despite that fertilization and implantation rates were similar in both groups, the cancellation rate was higher in the HH group (23.1% vs 0). However pregnancy and live birth rates were similar. CONCLUSIONS: The present study showed that HH women undergoing IVF/ICSI are good responders. The treatment of HH women with IVF/ICSI did not increase multiple pregnancies and OHSS rates over the TI group.

DNA repair genes in endometriosis.

Several polymorphisms in the DNA repair gene are thought to have significant effects on cancer risk. We investigated the association of polymorphisms in the DNA repair genes XRCC1 Arg399Gln, XRCC3 Thr241Met, XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, and HOGG1 Ser326Cys with endometriosis risk. Genotypes were determined by PCR-RFLP assays in 52 patients with endometriosis and 101 age-matched healthy controls. Although there were no significant (P > 0.05) differences in the frequencies of genotypes or alleles of APE1, XRCC1, XPD, XPG, and HOGG1 genes between patients and controls, the frequency of the XRCC3 Thr/Thr genotype was significantly greater in endometriosis patients compared with controls (P = 0.005). XRCC3 Thr/Met genotypes (P = 0.022), and the Met allele (P = 0.005) seem to have a protective role against endometriosis. The distributions of genotypes and alleles of the genes APE1, XRCC1, XRCC3, XPD, XPG, and HOGG1 were not significantly associated with the different stages of endometriosis (P > 0.05). We conclude that the XRCC3 Thr/Thr genotype is associated with endometriosis in Turkish women.

Knowledge and interest of Turkish women about cervical cancer and HPV vaccine.

OBJECTIVE: We aimed to evaluate the knowledge and interest level of Turkish women about HPV, HPV vaccines and cervical cancer using a questionaire. METHOD: A 25-item questionnaire was distributed to women in three different cities located in separate sociocultural locations. RESULTS: At the closure of the study 143 women responded and returned the survey. Of the participants 62.2% (89) had a university degree, 36.4% (52) a high school education, and 1.4% (2) had lower school degrees; 98.5% of the women would consent to have their daughter vaccinated for HPV and 94.7% would consent to have their son vaccinated if vaccine provided prevention against cancer and related diseases. However in both cases women gave importance to the "cost" - unless vaccine could be free. On logistic regression analyses none of the variables (i.e., questions) in the survey predicted women's willingness to accept the vaccine for themselves or their children. CONCLUSIONS: Women in Turkey would be willing to have themselves and their children receive HPV vaccine against cervical cancer and related diseases.

Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone.

The structures of the ligand-binding domains (LBD) of the wild-type androgen receptor (AR) and the T877A mutant corresponding to that in LNCaP cells, both bound to dihydrotestosterone, have been refined at 2.0 A resolution. In contrast to the homodimer seen in the retinoid-X receptor and estrogen receptor LBD structures, the AR LBD is monomeric, possibly because of the extended C terminus of AR, which lies in a groove at the dimerization interface. Binding of the natural ligand dihydrotestosterone by the mutant LBD involves interactions with the same residues as in the wild-type receptor, with the exception of the side chain of threonine 877, which is an alanine residue in the mutant. This structural difference in the binding pocket can explain the ability of the mutant AR found in LNCaP cells (T877A) to accommodate progesterone and other ligands that the wild-type receptor cannot.

Functional redundancy of the nuclear factor kappa B inhibitors I kappa B alpha and I kappa B beta.

The transcription factor NF-kappaB is sequestered in the cytoplasm by the inhibitor proteins of the IkappaB family. Each member of the IkappaB exhibits structural and biochemical similarities as well as differences. In an effort to address the functional redundancy of two closely related IkappaB molecules, IkappaBalpha and IkappaBbeta, we generated knock-in mice by replacing the IkappaBalpha gene with the IkappaBbeta gene. The knock-in mice do not express IkappaBalpha, but express a T7-tagged IkappaBbeta under the promoter and regulatory sequence of ikba. Unlike the IkappaBalpha-deficient mice, which display severe postnatal developmental defects and die by postnatal day 8, homozygous knock-in mice survive to adulthood, are fertile, and exhibit no apparent abnormalities. Furthermore, thymocytes and embryonic fibroblasts from the knock-in animals exhibit an inducible NF-kappaB response similar to that of wild-type animals. These results indicate that IkappaBalpha and IkappaBbeta share significant similarities in their biochemical activity, and that they acquired their different functions from divergent expression patterns during evolution.

Short-term urinary flow impairment deregulates PAX2 and PCNA expression and cell survival in fetal sheep kidneys.

Renal malformations account for most children with chronic renal failure and are often associated with urinary tract anatomical obstruction. We examined cellular and molecular events after experimental urinary flow impairment in fetal sheep. Ovine gestation lasts 144 to 150 days with the metanephros appearing at 27 to 30 days. We generated complete unilateral ureteric anatomical obstruction at 90 days when a few layers of glomeruli had formed. After 10 days, we recorded ureteric and pelvic dilatation with renal parenchymal weight greater than contralateral organs or those from unoperated fetuses. The nephrogenic cortex was replaced by disorganized cells separated by edema and prominent vascular spaces. Cortical histology was dominated by cysts associated with malformed glomerular tufts. Cystic epithelia expressed PAX2, a growth-stimulating transcription factor down-regulated during normal maturation, and proliferating cell nuclear antigen, a surrogate marker of cycling cells. Detection of apoptosis using propidium iodide and in situ end labeling showed a significant increase of the point prevalence of death in the obstructed cortex. Hence, PAX2 and proliferating cell nuclear antigen expression as well as death were deregulated, as we previously reported in human kidney malformations. Medullary collecting ducts and loops of Henle were also disrupted, correlating with impaired urinary dilution and sodium reabsorption. Therefore, complex aberrations of morphogenesis, gene expression, cell turnover, and urine composition occur relatively early after experimental impairment of fetal urinary flow.