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Biomedical subjects

S Manning

Publications and source records attributed to S Manning.

At least 19 recordsLinked to original sources
PubMed2001

15S-Hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated receptor gamma and inhibits proliferation in PC3 prostate carcinoma cells.

15-Lipoxygenase (15-LOX)-2 is expressed in benign prostate secretory cells and benign prostate produces 15S-hydroxyeicosatetraenoic acid (15S-HETE) from exogenous arachidonic acid (AA). In contrast, 15S-LOX-2 and 15S-HETE formation are reduced in prostate carcinoma (Pca). The mechanisms whereby reduced 15-LOX-2 may contribute to Pca development or progression are not known. We investigated the expression of peroxisome proliferator-activated receptor (PPAR) gamma in benign and malignant prostate tissues and the ability of 15S-HETE to activate PPARgamma-dependent transcription and modulate proliferation of the Pca cell line PC3. In contrast to benign prostate and similar to most Pca tissues, 15-LOX-2 mRNA was not detected in PC3 cells, and they did not produce detectable 15-HETE from [14C]AA. By reverse transcription-PCR, PPARgamma mRNA was present in 18 of 18 benign and 9 of 9 tumor specimens. The PPARgamma ligand BRL 49653 and 15S-HETE caused a dose-dependent inhibition of PC3 proliferation in a 14-day soft agar colony-forming assay (IC50 of 3 and 30 microM, respectively). 15S-HETE (10 microM) caused greater inhibition than 10 microM 15R-HETE. At 3 days, BRL 49653 and 15S-HETE caused a slight increase in cells in G0-G1 and a corresponding decrease in cells in S phase. In PC3 cells transiently transfected with a luciferase reporter linked to a PPAR response element, 1 microM BRL 49653 and 10 microM 15S-HETE caused approximately threefold and greater than twofold induction of PPAR-dependent transcription, respectively. By quantitative real-time reverse transcription-PCR and Northern analysis, 3-day treatment with BRL 49653 and 15S-HETE caused a reduction of PPARgamma expression but a marked up-regulation of the PPAR response element containing adipocyte type fatty acid binding protein. These results support the hypothesis that 15-LOX-2-derived 15S-HETE may constitute an endogenous ligand for PPARgamma in the prostate and that loss of this pathway by reduced expression of 15-LOX-2 may contribute to increased proliferation and reduced differentiation in prostate carcinoma.

Agar↗
PubMed2001

The curly tail mouse model of human neural tube defects demonstrates normal spinal cord differentiation at the level of the meningomyelocele: implications for fetal surgery.

The paralysis associated with lumbosacral meningomyelocele has been attributed both to myelodysplasia and to degeneration of the exposed neural tissue. Surgically created dysraphism shows that exposure of an intact spinal cord in a genetically normal animal results in degeneration of the normal nervous tissue and subsequent paralysis. Our objective was to study neuronal differentiation in the curly tail mouse mutant model, which develops lumbosacral meningomyelocele naturally and is a phenocopy of nonsyndromic human neural tube defects. Prenatal repair of meningomyelocele assumes that the normal neuronal differentiation program occurs despite failure of neurulation. Here we demonstrate that this most suitable animal model has normal differentiation of neuronal structures at the level of the meningomyelocele. TuJ1, an antibody to neuronal specific class III beta-tubulin, an early marker of neuronal differentiation, was used to stain paraffin-embedded sections of curly tail mouse embryo meningomyelocele. Embryos were examined at embryonic day 13.5 (E13.5). The inbred mouse strain, C57BL6/J, which is genetically similar to the curly tail mouse, was used as a control in these studies. We show that early neuronal differentiation appears intact within the meningomyelocele. TuJ stains structures within the open neural tube. Motor neurons are present in the ventral horn and ventral roots. Dorsal root ganglia are present and of similar size to controls. The staining pattern is similar to that seen in the C57BL/6J control mouse, although dorsal structures are laterally displaced in the curly tail meningomyelocele. Based on this model, fetal surgery to repair human meningomyelocele may preserve neurological function in those cases where there is not an inherent genetic defect of the neural tissue.

Animals↗
PubMed2001

Surgical intervention for sinusitis in children.

Pediatric rhinosinusitis represents a common endpoint of many potential etiologic factors, but fixed anatomic obstruction of sinus outflow is relatively unusual in pediatric patients. Surgical therapy is considered when medical therapy for underlying mucosal inflammation fails. Adenoidectomy is usually the first surgical intervention to be considered for young children, with the goal of improving sinus drainage and eliminating a potential source of bacteria. Endoscopic sinus surgery is considered for the small percentage of patients, most commonly those with underlying pulmonary disease, who fail less aggressive treatment measures. Every decision for surgery involves a risk-benefit analysis.

Child↗
PubMed2001

The amnionless gene, essential for mouse gastrulation, encodes a visceral-endoderm-specific protein with an extracellular cysteine-rich domain.

Fate-mapping experiments in the mouse have revealed that the primitive streak can be divided into three functional regions: the proximal region gives rise to germ cells and the extra-embryonic mesoderm of the yolk sac; the distal region generates cardiac mesoderm and node-derived axial mesendoderm; and the middle streak region produces the paraxial, intermediate and lateral plate mesoderm of the trunk. To gain insight into the mechanisms that mediate the assembly of the primitive streak into these functional regions, we have cloned and functionally identified the gene disrupted in the amnionless (amn) mouse, which has a recessive, embryonic lethal mutation that interferes specifically with the formation and/or specification of the middle primitive streak region during gastrulation. Here we report that the gene Amn encodes a novel type I transmembrane protein that is expressed exclusively in the extra-embryonic visceral endoderm layer during gastrulation. The extracellular region of the Amn protein contains a cysteine-rich domain with similarity to bone morphogenetic protein (BMP)-binding cysteine-rich domains in chordin, its Drosophila melanogaster homolog (Short gastrulation) and procollagen IIA (ref. 3). Our findings indicate that Amn may direct the production of trunk mesoderm derived from the middle streak by acting in the underlying visceral endoderm to modulate a BMP signaling pathway.

Amino Acid Sequence↗
PubMed2001

Experimental evaluation of vitellogenin as a predictive biomarker for reproductive disruption.

Vitellogenin (VTG) synthesis in male oviparous vertebrates is used as an indicator of environmental estrogen exposure, but the relationship between elevated VTG levels and the effects of environmental estrogens on reproductive success are poorly understood. To examine whether altered VTG expression predicts reproductive impairment, we exposed medaka (Oryzias latipes) for 2 or 8 weeks posthatch to 0, 0.5, 1.0, 2.5, and 7.5 ppb of the environmental estrogen o,p'-DDT. Fish were sampled 2, 4, and 8 weeks after hatch to examine VTG expression and gonad development. After exposure, fish were transferred to clean water, grown to sexual maturity, and placed in mating pairs. We collected eggs for 7 days and scored them for fecundity (number of eggs), fertility (percent fertilized), and hatching success (percent hatched). DDT had no effect on VTG expression after a 2-week exposure, whereas all doses induced VTG after 8 weeks. At both exposure durations, the highest doses of DDT caused a female-skewed sex ratio in adults. Gonadal feminization appeared to be progressive: some ovotestes were observed after 2- or 4-week exposure to the two highest doses, but the proportion of ovaries increased after 8 weeks. Both 2- and 8-week exposures significantly reduced fertility and hatching success at all doses, with lower doses having a greater effect after longer exposure. Fertility and hatching success were more sensitive to estrogenic disruption than were gonad differentiation and vitellogenin expression. We suggest that VTG expression may be interpreted as a warning of reproductive consequences, but absence of expression cannot be interpreted as absence of consequences.

Animals↗
PubMed2000

Prevalence and co-colonization with group b streptococcus (Gbs) Among heterosexual college couples.

PURPOSE: Maternal colonization with GBS is a major cause of neonatal sepsis and meningitis. While GBS transmission is assumed to be fecal-oral or person-to-person direct contact including possible sexual transmission, risk factors for colonization and carriage are poorly described. Basic descriptive epidemiologic information is needed in order to implement a prevention program such as the development of an effective vaccine.METHODS: As part of a study of heterosexual transmission of urinary tract infection (UTI), we describe the prevalence and co-colonization of GBS among college couples. Self-collected vaginal, urine and rectal specimens were cultured from women with UTI and their current sex partners ("case couples"), and from women without UTI and their current sex partners ("control couples").RESULTS: Thirty-four percent (98/285) of case women and 31% (56/182) of control women had at least one GBS isolate. 25% (45/177) of case men and 26% (32/122) of control men had at least one GBS isolate. Given that GBS was present in one partner, 45% of case (34/75) and 57% of control (24/42) couples were co-colonized. Using pulsed-field gel electrophoresis (PFGE) analysis, GBS isolates shared within couples were identical in most cases, but PFGE patterns differed across couples.CONCLUSIONS: Prevalence of GBS is high among sexually active college students and sexual contact is associated with increased transmission.

Journal Article↗
PubMed2000

Sialoblastoma of the submandibular gland: report of a case and review of the literature.

Sialoblastomas are rare perinatal epithelial salivary tumors, with only 22 reported cases in the literature. While they have been reported to occur predominantly in the parotid gland, we present one case of sialoblastoma of submandibular gland origin. The surgical management of this patient is discussed. Histopathologic examination, including immunochemical, ultrastructural and cytogenetic studies, was performed. Pertinent literature is reviewed.

Carcinoma↗
PubMed2000

The CD28-related molecule ICOS is required for effective T cell-dependent immune responses.

While CD28 is critical for expansion of naive T cells, recent evidence suggests that the activation of effector T cells is largely independent of CD28/B7. We suggest that ICOS, the third member of the CD28/CTLA-4 family, plays an important role in production of IL-2, IL-4, IL-5, and IFNgamma from recently activated T cells and contributes to T cell-dependent B help in vivo. Inhibition of ICOS attenuates lung mucosal inflammation induced by Th2 but not Th1 effector populations. Our data indicate a critical function for the third member of the CD28 family in T cell-dependent immune responses.

Abatacept↗
PubMed2000

Reduced 15-lipoxygenase-2 immunostaining in prostate adenocarcinoma: correlation with grade and expression in high-grade prostatic intraepithelial neoplasia.

Arachidonic acid (AA) metabolites are implicated in the oncogenesis of several tumors, including prostate cancer. 15-Lipoxygenase-2 (15-LOX-2) is a novel AA-metabolizing enzyme with a limited tissue distribution, which includes prostate, lung, skin, and cornea. Previous studies have shown that 15-LOX-2 is present in benign prostate secretory cells and reduced in prostate adenocarcinoma and that production of the 15-LOX-2 metabolite 15S-hydroxyeicosatetraenoic acid is reduced in malignant compared with benign prostate. The objective of this study was to determine the frequency with which 15-LOX-2 immunostaining is reduced in prostate carcinoma and to correlate reduced expression with tumor differentiation (grade) and other pathologic parameters in radical prostatectomy specimens. Paraffin immunoperoxidase with a polyclonal antibody specific for 15-LOX-2 was performed on tumors and benign portions from 70 cases, and the percentage of tumor immunostaining for 15-LOX-2 was assessed. Whereas uniform 15-LOX-2 immunostaining was observed in secretory cells of benign glands, it was markedly reduced or absent in most adenocarcinomas: 23 of 70 tumors showed completely absent 15-LOX-2 immunostaining, and 45 of 70 cases showed negative immunostaining in more than 50% of the tumor. The extent of reduced 15-LOX-2 immunostaining correlated with tumor differentiation, with retained expression particularly in Gleason score 5 tumors versus a significant reduction of 15-LOX-2 in higher-grade tumors (mean +/- SD tumor 15-LOX-2 positive: Gleason score 5 = 67%+/-30%, Gleason score 6 = 16%+/-30%, Gleason score 7 = 23%+/-28%, Gleason score > or =8 = 41%+/-46%). In 16 cases with multifocal tumors or different foci of the same tumor with different grades, the higher-grade foci had significantly reduced 15-LOX-2 expression compared with the lower-grade foci. In peripheral zone tumors without complete loss of 15-LOX-2 expression, there was a significant inverse relationship between 15-LOX-2 immunostaining and tumor volume. There was not a significant correlation between 15-LOX-2 immunostaining and serum PSA or pathologic stage. In a subset of 27 cases, 15-LOX-2 expression in high-grade prostatic intraepithelial neoplasia (HGPIN) glands was significantly reduced compared with benign glands. These data show that in contrast to the uniform expression of 15-LOX-2 in differentiated secretory cells of benign prostate, reduced 15-LOX-2 is a common alteration in prostate carcinoma, and this correlates with tumor cell differentiation. That reduced expression is seen in HGPIN suggests that this may be an early alteration in carcinoma development.

Adenocarcinoma↗
PubMed2000

Long-term pyrene exposure of grass shrimp, Palaemonetes pugio, affects molting and reproduction of exposed males and offspring of exposed females.

The objective of this study was to investigate the impact of long-term pyrene exposure on molting and reproduction in the model estuarine invertebrate, the grass shrimp (Palaemonetes pugio). Grass shrimp were exposed to measured concentrations of 5.1, 15.0, and 63. 4 ppb (microg/L) pyrene for 6 weeks, during which time we determined molting and survivorship. At the end of the exposure, we immediately sacrificed some of the shrimp for biomarker (CYP1A and vitellin) analyses. The remaining shrimp were used to analyze fecundity and embryo survivorship during an additional 6 weeks after termination of pyrene exposure. Male shrimp at the highest pyrene dose (63 ppb) experienced a significant delay in molting and in time until reproduction, and showed elevated ethoxycoumarin o-deethylase (ECOD) activity immediately after the 6-week exposure period. In contrast, 63 ppb pyrene did not affect these parameters in female shrimp. Females produced the same number of eggs per body weight, with high egg viability (98-100%) at all exposure levels, but with decreased survival for the offspring of the 63-ppb pyrene-exposed females. In addition, vitellin levels were elevated only in females at 63 ppb pyrene after the 6-week exposure. We hypothesize that the elevated vitellin binds pyrene and keeps it biologically unavailable to adult females, resulting in maternal transfer of pyrene to the embryos. This would account for the lack of effect of pyrene exposure on ECOD activity, molting, and reproduction in the adult females, and for reduced survival of their offspring.

Animals↗
PubMed2000

Creating a space: when to extract.

The decision to provide root canal treatment is based on the desire of the patient to keep his or her tooth and likelihood of success. As there are good options for the replacement of teeth the success of root canal treatment should be weighed against these alternatives. This paper aims to review the literature and give an insight into the factors affecting endodontic success and when it may be best to create a space with extraction.

Decision Making↗
PubMed1999

NHS values. I want to tell you a story.

Many NHS staff feel that they are unable to put their values into action because of the constraints on the service. They want a working environment where trust is possible and mistakes can be made without retribution. The reality is often bullying and attempts at innovation being met with reproach.

Attitude of Health Personnel↗
PubMed1999

Serum vitellogenin levels and reproductive impairment of male Japanese Medaka (Oryzias latipes) exposed to 4-tert-octylphenol.

The induction of synthesis of the "female" yolk precursor protein vitellogenin (VTG) in male fish by estrogenic chemicals in the environment has been demonstrated in many recent reports. However, little is known about the organismal and biological significance of this phenomenon. To examine the relationship between VTG production in male fish and reproductive impairment, adult male medaka were exposed to 4-tert-octylphenol (OP), a known environmental estrogen, in concentrations ranging from 20 to 230 ppb for 21 days, under flow-through conditions. Following exposure, male fish were mated, in the absence of OP, with unexposed females. Breeding groups composed of exposed males and control females produced about 50% fewer eggs than control groups. VTG levels in serum of male fish increased with increasing OP exposure concentration and decreased after OP exposure was discontinued. Nevertheless, significant correlations (p<0.01) were observed between VTG levels in exposed male fish and 1) OP exposure concentrations, 2) percent of fertilized eggs, and 3) survival of embryos. OP-induced VTG synthesis and reproductive impairment appear to be closely linked phenomena. Histological examination indicated spermatogenesis in OP-exposed fish was inhibited, and some exposed fish had oocytes in their testes. Finally, OP caused a significant increase in the number of abnormally developing embryos, suggesting that OP may be genotoxic as well as estrogenic.

Animals↗
PubMed1998

NHS values. What are we here for?

Following more than a decade of change, the NHS is keen to explore the values driving its daily life. Consistency between values and behaviour are an important part of building an organisation's identity and confidence. It is likely that pluralistic values inform the NHS more now than was the case in the early years of the welfare state.

Organizational Culture↗
PubMed1998

Monoclonality in fibroadenomas with complex histology and phyllodal features.

Fibroadenoma is a common cause of benign breast masses in young women. These women have a slightly increased risk of subsequent breast cancer, particularly if their tumors have complex histologic patterns. We assessed monoclonality in fibroadenomas and correlated the results with histologic analysis. We performed a clonal analysis of 52 fibroadenomas from 43 patients using X-chromosome inactivation studies. The cases included fibroadenomas with complex and simple histology. Areas examined were predominantly stroma but epithelium was also present. DNA was isolated from paraffin-embedded tissue and was subjected to polymerase chain reaction amplification of the human androgen receptor gene with and without predigestion of the DNA with Hha 1. If a monoclonal process was identified, the epithelial and stromal components were subsequently microdissected and reanalyzed. 36/43 (83.7%) women were heterozygous. We studied 45 tumors in these 36 informative women. 1/20 (5% complex fibroadenomas and 1/25 (4%) simple fibroadenomas were monoclonal. The epithelial component of both monoclonal fibroadenomas was polyclonal. The one monoclonal simple fibroadenoma was also the only one with mixed features to contain a phyllodes component. In this case, monoclonality was found in the stroma of both the fibroadenoma and phyllodes regions. Monoclonality has been previously associated with phyllodes phenotype, but not with fibroadenomas, except for 3 fibroadenomas that recurred as phyllodes tumor. We report that monoclonality may also be seen occasionally in complex fibroadenomas, and was found in a tumors with mixed fibroadenoma/phyllodes features without clinical recurrence for 4 years.

Breast Neoplasms↗
PubMed1998

Repeated evolution of an acetate-crossfeeding polymorphism in long-term populations of Escherichia coli.

Six out of 12 independent replicate populations of Escherichia coli maintained in long-term glucose-limited continuous culture for up to approximately 1,750 generations evolve polymorphisms maintained by acetate crossfeeding. In all cases, the acetate-crossfeeding phenotype is associated with semiconstitutive overexpression of acetyl CoA synthetase, which allows for the enhanced uptake of low levels of exogenous acetate. Mutations in the 5' regulatory region of the acetyl CoA synthetase locus are responsible for all the acetate crossfeeding phenotypes found. These changes were either transposable-element insertions or a single T-->A nucleotide substitution at position -93 relative to the acs gene translation start site.

Acetate-CoA Ligase↗