Stem cell marker prominin‐1 regulates branching morphogenesis,but not regenerative capacity,in the mammary gland

Prominin‐1 (Prom1) is recognized as a stem cell marker in several tissues, including blood, neuroepithelium, and gut, and in human and mouse embryos and many cancers. Although Prom1 is routinely used as a marker for isolating stem cells, its biological function remains unclear. Here we use a knockout model to investigate the role of Prom1 in the mammary gland. We demonstrate that complete loss of Prom1 does not affect the regenerative capacity of the mammary epithelium. Surprisingly, we also show that in the absence of Prom1, mammary glands have reduced ductal branching, and an increased ratio of luminal to basal cells. The effects of Prom1 loss in the mammary gland are associated with decreased expression of prolactin receptor and matrix metalloproteinase‐3. These experiments reveal a novel, functional role for Prom1 that is not related to stem cell activity, and demonstrate the importance of tissue‐specific characterization of putative stem cell markers. Developmental Dynamics 240:674–681, 2011. © 2011 Wiley‐Liss, Inc.     

Immunologically reactive <Emphasis Type="Italic">M. leprae</Emphasis> antigens with relevance to diagnosis and vaccine development

Background  

Leprosy is a chronic infectious disease caused by Mycobacterium leprae that can manifest a wide variety of immunological and clinical outcomes ranging from potent humoral responses among borderline lepromatous (BL) and lepromatous (LL) patients to strong cellular responses among tuberculoid (TT) and borderline tuberculoid (BT) patients. Until recently, relatively little has been known about the immune responses to individual proteins of M. leprae recognized during leprosy.     

Practical problems posed by toxoplasmosis during pregnancy

The occurrence of toxoplasmosis during pregnancy raises numerous problems. Determination of the time of the maternal infection is the first problem since we know that the frequency and gravity of fetal involvement vary according to the term of the pregnancy. Then, with information obtained from prenatal diagnostic tests (sonogram, amniocentesis, fetal blood sampling), it is important to recognize infected fetuses and advocate a management which goes beyond therapeutic abortion. Finally, the final problem is the follow-up of these children; in fact, after all these diagnostic and therapeutic measures, it is unfortunate that many children become lost to follow-up after the first year.     

Treatment of stress urinary incontinence. Experience at the Gynecology-Obstetrics Center of Amiens

The authors report their experience of the surgical treatment of stress urinary incontinence. They underline the value of urodynamic tests in the examinations for urinary continence and prolapses. In the presence of a transmission defect, three different techniques are used: indirect colpopexy by strips (Loffredo) in the absence of prolapse, mixed route using vaginal strips (Bologna) in case of cystocele, sub-urethral plication reserved for elderly patients presenting a prolapse with stress urinary incontinence revealed by the urodynamic tests. The follow-up of the patients treated by the Loffredo technique is studied: 92% of good middle-term results (after 5 years).     

Sleeping position and sudden infant death syndrome (SIDS): effect of an intervention programme to avoid prone sleeping

The proportion of prone sleeping among sudden infant death syndrome (SIDS) victims and infants in general, and the rate of SIDS were prospectively studied in the county of Hordaland, Norway, three years before (1987–89) and three years after (1990–92) a campaign to discourage prone sleeping. Before the campaign, 64% of random reference infants were put prone versus 8% after (p < 0.0001). Concurrently, the rate of SIDS decreased from 3.5 to 1.6 per 1000 live births (63 infants before and 30 after the campaign, p = 0.0002). Prone sleeping was not considered a statistically significant risk factor for SIDS before (OR 2.0,95% CI 0.8–4.5), but was highly significant (OR 11.3,95% CI 3.6–36.5) after the campaign. Prone sleeping is an important risk factor for SIDS, but the association may be missed in epidemiological studies if prone is the predominant sleeping position. Behaviour with regard to sleeping position may be changed rapidly by means of a simple campaign.     

Acute rejection in the elderly recipient: Influence of age in the outcome of kidney transplantation

Since the immune response in older recipientsis weaker they should be less likely to rejecta transplanted organ and should need lessaggressive immunosuppressive treatment. Our aimwas to record the incidence and severity ofepisodes of acute rejection (AR), estimate theinfluence of these events on graft survival ofelderly recipients (60) and to comparethese with that in younger ones.We performed 363 kidney transplants between1/94 and 12/98, and recorded clinical andimmunological data, incidence-severity of ARand cause of graft loss. Patients were dividedinto two groups, according to the age attransplantation: A (<60, n = 281/77.4%) and B( 60, n = 82/22.6%). The percentage ofaging recipients and mean age of donors andrecipients increased throughout the period.Although the incidence of ATN was higher in theolder group (29% vs.19%, p < 0.0001) thenumber of graft biopsies was equal in bothgroups. The incidence of AR was similar, 33.4%vs. 26.8%, pNS. The number of AR episodes perpatient was 0.44 and 0.41 respectively. Theseverity of AR was: Banff grade I: A (40.3%)/B (45.7%) pNS; grade II: A (44.1%)/B(48.57) pNS; grade III: A (15.5%)/B (5.7%)pNS. Younger recipients presented a higherlevel of panel-reactive antibodies (PRA) (4.3%vs. 2.07%, p = 0.01). One-year patient survivalwas 96%/91% (p<0.05) and graft survivalwas 81%/78% (pNS) respectively.The age of recipient does not seem to haveinfluenced the incidence-severity of AR or thegraft survival. Thus immunosuppression shouldbe individualised for each patient and shouldnot depend on the age at transplantation.     

Lack of effect of testosterone and dihydrotestosterone compared to 17beta-oestradiol in 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine-mice

Previous work from our laboratory has demonstrated prevention of 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine (MPTP)-induced striatal dopamine depletion in C57Bl/6 mice by 17beta-oestradiol, progesterone and raloxifene. The activity of androgenic compounds in MPTP mice has received less attention and was the object of the present investigation. The effects of 17beta-oestradiol (2 microg/day), testosterone (100 microg/day) and dihydrotestosterone (DHT) (2 microg/day or 100 microg/day) were studied during 5 days before and after an acute treatment of four MPTP (10 mg/kg) injections in male C57Bl/6 mice. Striatal concentrations of dopamine and its metabolites dihydroxyphenylacetic acid and homovanillic acid were measured by high-performance liquid chromatography. MPTP mice treated with saline showed large decreases in dopamine and its metabolites compared to control mice. 17beta-oestradiol partially spared this decrease whereas testosterone and DHT did not. Striatal specific binding to the dopamine transporter (DAT) and to the vesicular monoamine transporter (VMAT2) were measured using [125I] RTI-121 and [3H] dihydrotetrabenazine autoradiography, respectively. As with striatal dopamine concentrations, MPTP treatment caused a decrease in DAT and VMAT2 specific binding. 17beta-oestradiol partially spared this decrease, whereas androgens did not. In the substantia nigra, DAT mRNA was measured by in situ hybridization. MPTP treatment induced a significant, but smaller decrease in substantia nigra DAT mRNA than striatal DAT protein. In addition, 17beta-oestradiol completely prevented the MPTP-induced decrease of DAT mRNA, whereas androgens did not. The present results show that androgens are unable to protect against MPTP-induced dopaminergic toxicity.     

Identification of the key amino acids of gliai cell line-derived neurotrophic factor family receptor alpha 1 involved in its biological function

Glial cell line-derived neurotrophic factor （GDNF） plays a critical role in neurodevelopment and survival of midbrain dopaminergic and spinal motor neurons in vitro and in vivo. The biological actions of GDNF are mediated by a two-receptor complex consisting of a glycosylphosphatidylinositol-linked cell surface molecule, the GDNF family receptor alpha 1 （GFR alpha 1）, and receptor protein tyrosine kinase Ret. Although structural analysis of GDNF has been extensively examined, less is known about the structural basis of GFR alpha 1 function. In this study, based on evolutionary trace method and relative solvent accessibility prediction of residues, a set of trace residues that are solvent-accessible was selected for site-directed mutagenesis. A series of GFR alpha 1 mutations was made, and PC12 cell lines stably expressing different GFR alpha 1 mutants were generated. According to the survival and differentiation responses of these stable PC12 cells upon GDNF stimulation and the GDNF- GFR alpha 1-Ret interaction assay, residues 152NN153, Arg259, and 316SNS318 in the GFR alpha 1 central region were found to be critical for GFR alpha 1 binding to GDNF and eliciting downstream signal transduction. The single mutation R259A in the GFR alpha 1 molecule simultaneously lost its binding ability to GDNF and Ret. However N152A/N153A or S316A/N317A/ S318A mutation in the GFR alpha 1 molecule still retained the ability to bind with Ret. These findings suggest that distinct structural elements in GFR alpha 1 may be involved in binding to GDNF and Ret.     

Practice MRI: Reducing the need for sedation and general anaesthesia in children undergoing MRI

The aim of this study was to evaluate the effectiveness of a practice magnetic resonance unit, in preparing children to undergo magnetic resonance procedures without general anaesthesia (GA) or sedation. The records of children who attended the practice MRI between February 2002 and April 2004 were retrospectively reviewed. Each record was assessed as to whether the child had passed or failed the practice MRI intervention. Those children who were considered to have passed and were proceeded to a clinical non‐GA MRI had the report of the clinical scan reviewed. If the scan had been reported as non‐diagnostic because of movement artefact it was classified as a failed scan, otherwise it was considered a pass. One hundred and thirty‐four children undertook a practice MRI (age range 4.1–16.1 years, median age 7.7 years, 47% boys) and 120/134 (90%) passed the practice session. In all, 117/120 (98%) subsequently had a clinical non‐GA MRI and 110/117 (94%) passed (median age 7.8 years, 47% boys). Preparation is a safe and effective method to reduce the need for sedation and GA in children undergoing a clinical MRI scan. It provides a positive medical experience for children, parents and staff, and results in cost savings for the hospital.