Generation of HSCs in the embryo and assays to detect them

The precise temporal and spatial emergence of hematopoietic stem cells (HSC) in the murine embryo has been somewhat controversial largely due to differences in the assays utilized to demonstrate HSC repopulating ability. One strategy is to determine where and when one can first detect HSC that engraft upon transplantation into lethally irradiated adult mice. However, knowing that the primary sites and patterns of hematopoiesis change during ontogeny, an alternative strategy is to select transplantation models where the recipient subjects more closely mirror the stage of development of the donor cells. In this regard, perhaps the most relevant assay to determine the presence of HSC activity in the early embryo is to transplant the donor cells in utero into recipient embryos. Other recipient models that may permit engraftment of embryonic cells include the use of submyeloablated or genetically HSC deficient newborn mice. Additional informative strategies have included co-culturing embryonic tissues that appear to lack HSC activity, with stromal cells derived from different developmental sites of hematopoiesis to induce HSC emergence, followed by transplantation as a means to determine which embryonic tissues possess HSC potential. This review will highlight some of the various transplantation assays used to identify HSC from embryonic tissues.     

Enhancing power while controlling family-wise error: an illustration of the issues using electrocortical studies

This study examined the relative family-wise error (FWE) rate and statistical power of multivariate permutation tests (MPTs), Bonferroni-adjusted alpha, and uncorrected-alpha tests of significance for bivariate associations. Although there are many previous applications of MPTs, this is the first to apply it to testing bivariate associations. Electrocortical studies were selected as an example class because the sample sizes that are typical of electrocortical studies published in 2001 and 2002 are small and their multiple significance tests are typically nonindependent. Because Bonferroni adjustments assume independent predictors, we expected that MPTs would be more powerful than the Bonferroni adjustment. Results support the following conclusions: (a) failure to control for multiple significance testing results in unacceptable FWE rates, (b) the FWE rate for the MPTs approximated the alpha set for the analyses, and (c) the statistical power advantage that MPTs provide over Bonferroni adjustments is important when using small sample sizes such as those that are typical of recent electrocortical studies.     

The pattern of cerebral injury in a primate model of preterm birth and neonatal intensive care

Survivors of very premature birth face an increased risk of adverse motor, cognitive, and behavior sequelae. In order to understand the pathogenesis of these adverse outcomes, an animal model of premature birth and neonatal care in a species with a close similarity to the human infant is sought. In this histological and immunohistochemical study we have defined the pattern of cerebral injury in a premature baboon model undergoing similar neonatal intensive care to that of the human premature infant. Sixteen baboons were delivered at 125 days gestation (dg; term approximately184 dg) with 14 days neonatal intensive care and were compared with gestational control brains at 125, 140, and 160 dg. The premature baboons undergoing neonatal intensive care sustained a spectrum of neuropathologies including white matter injury, hemorrhage, and ventriculomegaly, which resemble lesions frequently observed in the human premature infant. These data suggest that the premature baboon is a model with similarities in maturation and pattern of cerebral injury to the human infant that may provide useful insights of relevance to the human preterm infant.     

Sequence conservation and distribution of the fusobacterial immunosuppressive protein gene,fipA

Fusobacterium nucleatum is a gram-negative anaerobe involved in various diseases, including periodontitis. Recently, other investigators isolated the F. nucleatum FDC 364 fusobacterial immunosuppressive protein (FIP). One subunit, FipA, impairs T-cell activation in vitro and shows homology with beta-ketothiolases. However, its distribution and variability among fusobacteria was not reported. Cloned fipA gene sequences from F. nucleatum ssp. polymorphum (ATCC 10953) and F. nucleatum ssp. nucleatum (ATCC 23726) shared 89 and 92% identity, respectively, with FDC 364 fipA, and 90 and 94% identity, respectively, with the FDC 364 FipA predicted amino acid sequence. Southern blot analyses of chromosomal DNA from fusobacterial strains, including F. nucleatum and other Fusobacterium species, were performed using partial fipA sequences as probes. The results indicate that fipA is highly conserved among the F. nucleatum strains examined and that fipA homologues are widely distributed among fusobacteria. A clear relationship between immune suppression, metabolism and the FipA protein remains to be determined.     

The prevalence of men with National Institutes of Health category IV prostatitis and association with serum prostate specific antigen

PURPOSE: We evaluated the prevalence and relationship of serum prostate specific antigen (PSA) levels in a screening population of men diagnosed with National Institutes of Health (NIH) category IV prostatitis. MATERIALS AND METHODS: In September of 2001, 300 men were randomly selected from our prostate cancer awareness screening program to be evaluated for NIH category IV prostatitis. After informed consent was obtained all patients completed the NIH prostate cancer awareness survey and had a serum sample obtained for PSA before examination. Expressed prostatic secretions were obtained from 227 of the 300 participants. Patients were classified according to findings on examination of the expressed prostatic secretions. The records were entered into our data base and subsequently reviewed. RESULTS: The prevalence of NIH category IV prostatitis was 32.2% in our population of men. Patient age, American Urological Association symptom scores and clinical prostate gland size did not differ between men with or without evidence of prostatitis on expressed prostatic secretion examination. Men with NIH category IV prostatitis had a mean serum PSA level of 2.3 which was significantly higher (p <0.0004) than those without prostatitis (mean PSA 1.4). CONCLUSIONS: These data suggest that NIH category IV prostatitis is fairly prevalent (32.2%) among men in the general population who present for prostate cancer screening and appears to contribute to increased serum PSA levels in some men.     

Single versus repeated-course antenatal corticosteroids: outcomes in singleton and multiple-gestation pregnancies

The objectives of this study are to compare the neonatal risks and benefits of antenatal single-course versus repeated-course corticosteroids in singleton and multiple-gestation pregnancies. A comprehensive analysis was performed of the inpatient records of all neonates admitted to our center from 1 January 1994 through 31 May 1999. The primary outcome measure was survival without chronic lung disease (CLD). Secondary outcome measures included birth weight; head circumference; interval weight ratios; respiratory disease severity; intraventricular hemorrhage rate and severity; severe retinopathy of prematurity; early infection; and hospital days. All singletons 27-32 completed weeks' gestation, and multiples 26-32 weeks' gestation, whose mothers had received betamethasone before delivery, were included. One hundred and fifteen singleton and 53 multiple-gestation infants (total 168) were stratified by multiplicity, gestational-age (< or =29 or > or =30 weeks), and number of steroid courses. Repeated courses of antenatal betamethasone were not associated with greater survival without CLD, in either singleton- or multiple-gestation infants. In singletons there was no difference in any outcome measure between groups. In multiples, the only difference was greater postnatal weight gain in the lower gestation group. Mean birth head circumference was smaller in repetitively-treated singletons < or =29 weeks. There are no clinically significant neonatal benefits of repeated-course antenatal steroids in singletons > or =27 weeks estimated gestational age (EGA) or multiple-gestation infants > or =26 weeks EGA. Prospective randomized trials of single-course versus repetitive antenatal corticosteroid therapy are warranted.