Changes in body-related self-conscious emotions over time among youth female athletes.

The current study explored change in body-related self-conscious emotions (e.g., shame, guilt, authentic pride, hubristic pride) over three years, and tested body surveillance, age, weight status, years in sport, and competitive status as baseline predictors of change. Adolescent females engaged in organized sport (N = 518 at baseline, Mage = 14.02, SD = 1.38 years) completed a self-report survey once a year for three years (n = 293 and n = 215 in Years 2 and 3, respectively). Based on the unconditional latent growth model, body-related shame and guilt increased over time, and authentic and hubristic pride decreased over time. There was substantial between-person variability in the intercepts for all emotions and slopes for shame, guilt, and hubristic pride. In the conditional parallel process latent growth model, body surveillance predicted shallower change in shame and guilt over time. Female athletes high in body surveillance also reported higher body-related shame and guilt and lower authentic and hubristic pride at baseline. These findings highlight the importance of studying changes in self-conscious emotions over time in sport, and demonstrate that body surveillance may be an important factor to explore in interventions early in development.

Making a move in exercise referral: co-development of a physical activity referral scheme.

Background: Translational research is required to ensure exercise referral schemes (ERSs) are evidence-based and reflect local needs. This article reports process data from the co-development phase of an ERS, providing an insight into (i) factors that must be considered when translating evidence to practice in an ERS setting, and (ii) challenges and facilitators of conducting participatory research involving multiple stakeholders. Methods: An ERS was iteratively co-developed by a multidisciplinary stakeholder group (commissioners, managers, practitioners, patients and academics) via five participatory meetings and an online survey. Audio data (e.g. group discussions) and visual data (e.g. whiteboard notes) were recorded and analysed using NVivo-10 electronic software. Results: Factors to consider when translating evidence to practice in an ERS setting included (i) current ERS culture; (ii) skills, safety and accountability; and (iii) resources and capacity. The co-development process was facilitated by needs-analysis, open questions, multidisciplinary debate and reflective practice. Challenges included contrasting views, irregular attendance and (mis)perceptions of evaluation. Conclusion: The multidisciplinary co-development process highlighted cultural and pragmatic issues related to exercise referral provision, resulting in an evidence-based intervention framework designed to be implemented within existing infrastructures. Further work is required to establish the feasibility and effectiveness of the co-developed intervention in practice.

Standards of reporting: the use of CONSORT PRO and CERT in individuals living with osteoporosis.

The Consolidated Standards of Reporting Trials for Patient-Reported Outcomes (CONSORT PRO) and the Consensus on Exercise Reporting Template (CERT) have been developed to improve the quality and transparency of reporting standards in scientific research. The purpose of this study was to provide evidence for the adoption of CONSORT PRO and CERT by researchers examining the link between exercise and quality of life in individuals living with osteoporosis. A systematic search was conducted to identify randomized control trials published in English evaluating exercise interventions on quality of life in individuals living with osteoporosis. Reporting standards were assessed using CONSORT PRO and CERT. A total of 127 studies were identified with 23 meeting inclusion criteria. "Good" evidence for eight (42.1%) CONSORT PRO and two (12.5%) CERT items was found. Adherence to CONSORT PRO was not related to the year of publication, journal impact factor, or study quality. Adherence to CONSORT PRO and CERT reporting standards is inadequate in the literature examining exercise interventions on quality of life in individuals living with osteoporosis. Sufficient reporting is paramount to knowledge translation, interpretation by interventionists, and clinician confidence in understanding if (and how) exercise is associated with quality of life outcomes in this cohort. Concerns associated with failure to include this information are highlighted.

Insulin-like growth factor receptor polymorphism defines clinical outcome in estrogen receptor-positive breast cancer patients treated with tamoxifen.

Compelling evidence points to a key role for insulin-like growth factor 1 (IGF1) signaling in breast cancer development and progression. In addition, IGF1 receptor (IGF1R) expression has been correlated and functionally linked with estrogen receptor (ER) signaling. Recent translational studies support a cross talk between IGF1R and ERα at different levels and data suggest enhanced IGF1R signaling as a causative mechanism of tamoxifen (TAM) resistance. We tested whether functional germline variations in the IGF pathway are associated with clinical outcome in ER-positive primary invasive breast cancer patients, who were treated with surgery and adjuvant TAM. Tissue samples of 222 patients with ER+ primary invasive breast cancer, who had undergone surgery at Charing Cross Hospital, London, UK between 1981 and 2003, were analyzed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue samples and six functional IGF1 pathway polymorphisms were analyzed using direct DNA sequencing and PCR-restriction fragment length polymorphism. In multivariable analysis, patients with primary invasive breast cancer carrying IGF1R_rs2016347 G allele had a significantly increased risk of early tumor progression (hazard ratio (HR) 2.01; adjusted P=0.004) and death (HR 1.84; adjusted P=0.023) compared with patients carrying G/T or T/T, independent of established clinicopathological determinants. This association remained significant after adjusting for multiple testing. In addition, we were able to demonstrate that IRS1_rs1801123 and IGFBP3_rs2854744 were significantly associated with lymph node involvement and tumor size, respectively. We provide the first evidence for IGF1R_rs2016347 as an independent prognostic marker for ER+ breast cancer patients treated with TAM and support a rational for combined treatment strategies.

Intratumoral expression profiling of genes involved in angiogenesis in colorectal cancer patients treated with chemotherapy plus the VEGFR inhibitor PTK787/ZK 222584 (vatalanib).

The phase III CONFIRM clinical trials demonstrated that metastatic colorectal cancer patients with elevated serum lactate dehydrogenase (LDH) had improved outcome when the vascular endothelial growth factor receptor (VEGFR) inhibitor PTK/ZK (Vatalanib) was added to FOLFOX4 chemotherapy. We investigated the hypothesis that high intratumoral expression of genes regulated by hypoxia-inducible factor-1 alpha (HIF1α), namely LDHA, glucose transporter-1 (GLUT-1), VEGFA, VEGFR1, and VEGFR2, were predictive of outcome in CONFIRM-1. Tumor tissue was isolated by laser-capture microdissection from 85 CONFIRM-1 tumor specimens; FOLFOX4/placebo n=42, FOLFOX4/PTK/ZK n=43. Gene expression was analyzed using quantitative RT-PCR. In univariate analyses, elevated mRNA expression of LDHA, GLUT-1, and VEGFR1 were associated with response to FOLFOX4/PTK/ZK. In univariate and multivariate analyses, elevated LDHA and VEGFR1 mRNA levels were associated with improved progression-free survival in FOLFOX4/PTK/ZK patients. Furthermore, increased HIF1α and VEGFR2 mRNA levels were associated with decreased survival in FOLFOX/placebo patients but not in patients who received FOLFOX4/PTK/ZK. These are the first data suggesting intratumoral mRNA expression of genes involved in angiogenesis/HIF pathway may predict outcome to VEGFR-inhibitors. Biomarkers that assist in directing VEGFR-inhibitors toward patients with an increased likelihood of benefit will improve the cost-effectiveness of these promising agents.

An individual coding polymorphism and the haplotype of the SPARC gene predict gastric cancer recurrence.

The 5-year survival rate for gastric adenocarcinoma (GA) remains only 40% and biomarkers to identify patients at high risk of tumor recurrence are urgently needed. Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix glycoprotein that mediates cell matrix interactions, and upregulation of SPARC can promote tumor progression and metastasis. This study investigated whether single-nucleotide polymorphisms (SNPs) in SPARC impact the prognosis of GA. Blood or formalin-fixed, paraffin-embedded tissues were obtained from 137 GA patients at the University of Southern California and Memorial Sloan-Kettering Cancer Center medical facilities. DNA was isolated and five SNPs in the SPARC 3'-untranslated region (UTR) were evaluated by DNA sequencing or PCR-restriction fragment length polymorphism. Associations between SNPs and time to tumor recurrence (TTR) were analyzed using Kaplan-Meier curves, log-rank tests, and likelihood-ratio test within logistic or Cox regression model as appropriate. Patients carrying at least one G allele of the SPARC rs1059829 polymorphism (GG, AG) showed a median TTR of 3.7 years compared with 2.1 years TTR for patients with AA (hazard ratio (HR) 0.57; P=0.033). In a multivariate analysis adjusted for T and N category as covariates and stratified by race, hospital and chemotherapy, patients with at least one SPARC rs1059829 G allele (GG, AG) remained significantly associated with superior TTR than patients with AA genotype (adjusted P=0.026). In addition, patients harboring the G-A-A haplotype had the highest risk of tumor recurrence (HR 1.892; adjusted P=0.016). Our findings suggest that SPARC 3'-UTR SNPs may be useful in predicting GA patients at increased risk of recurrence.

The Cyclin D1 (CCND1) A870G polymorphism predicts clinical outcome to lapatinib and capecitabine in HER2-positive metastatic breast cancer.

BACKGROUND: Lapatinib plus capecitabine emerged as an efficacious therapy in metastatic breast cancer (mBC). We aimed to identify germline single-nucleotide polymorphisms (SNPs) in genes involved in capecitabine catabolism and human epidermal receptor signaling that were associated with clinical outcome to assist in selecting patients likely to benefit from this combination. PATIENTS AND METHODS: DNA was extracted from 240 of 399 patients enrolled in EGF100151 clinical trial (NCT00078572; clinicaltrials.gov) and SNPs were successfully evaluated in 234 patients. The associations between SNPs and clinical outcome were analyzed using Fisher's exact test, Kaplan-Meier curves, log-rank tests, likelihood ratio test within logistic or Cox regression model, as appropriate. RESULTS: There were significant interactions between CCND1 A870G and clinical outcome. Patients carrying the A-allele were more likely to benefit from lapatinib plus capecitabine versus capecitabine when compared with patients harboring G/G (P = 0.022, 0.024 and 0.04, respectively). In patients with the A-allele, the response rate (RR) was significantly higher with lapatinib plus capecitabine (35%) compared with capecitabine (11%; P = 0.001) but not between treatments in patients with G/G (RR = 24% and 32%, respectively; P = 0.85). Time to tumor progression (TTP) was longer in patients with the A-allele treated with lapatinib plus capecitabine compared with capecitabine (median TTP = 7.9 and 3.4 months; P < 0.001), but not in patients with G/G (median TTP = 6.1 and 6.6 months; P = 0.92). CONCLUSION: Our findings suggest that CCND1A870G may be useful in predicting clinical outcome in HER2-positive mBC patients treated with lapatinib plus capecitabine.

GRP78 promoter polymorphism rs391957 as potential predictor for clinical outcome in gastric and colorectal cancer patients.

BACKGROUND: Recently, the analysis of gastric and colorectal tumor specimens determined that 78-kiloDalton glucose-regulated protein (GRP78), an endoplasmic reticulum chaperone, up-regulation serves as an efficient mechanism protecting cells against apoptosis and can confer drug resistance. We tested whether functional polymorphisms within the GRP78 gene are related to clinical outcome in gastric and colorectal cancer (CRC) patients. PATIENTS AND METHODS: Blood samples of 234 stage II/III CRC patients at the University of Southern California (USC) and formalin-fixed paraffin-embedded tissues of 137 patients with localized gastric adenocarcinoma (GA) at USC and Memorial Sloan-Kettering Cancer Centers were obtained. GRP78 polymorphisms analyzed on germline DNA were correlated with clinical outcome using univariate and multivariate analyses. RESULTS: GA patients with the combined GRP78 rs391957 C/T and T/T genotype were at higher risk for tumor recurrence and death [hazard ratio (HR) 2.61; P < 0.001 and HR 3.17; P < 0.001, respectively], than those with C/C. These findings were subsequently tested in a CRC cohort where patients with the homozygous T/T genotype were at highest risk for tumor recurrence (HR 2.61; P = 0.015). The results remained significant after adjusting for clinicopathologic determinants. CONCLUSION: These data provide the first evidence that the GRP78 rs391957 polymorphism can predict clinical outcome in localized GA and locally advanced CRC patients.

A let-7 microRNA-binding site polymorphism in 3'-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer treated with cetuximab monotherapy.

PURPOSE: recent studies have found that KRAS mutations predict resistance to monoclonal antibodies targeting the epidermal growth factor receptor in metastatic colorectal cancer (mCRC). A polymorphism in a let-7 microRNA complementary site (lcs6) in the KRAS 3' untranslated region (UTR) is associated with an increased cancer risk in non-small-cell lung cancer and reduced overall survival (OS) in oral cancers. We tested the hypothesis whether this polymorphism may be associated with clinical outcome in KRAS wild-type (KRASwt) mCRC patients treated with cetuximab monotherapy. PATIENTS AND METHODS: the presence of KRAS let-7 lcs6 polymorphism was evaluated in 130 mCRC patients who were enrolled in a phase II study of cetuximab monotherapy (IMCL-0144). Genomic DNA was extracted from dissected formalin-fixed paraffin-embedded tumor tissue, KRAS mutation status and polymorphism were assessed using direct sequencing and PCR restriction fragment length polymorphism technique. RESULTS: KRAS let-7 lcs6 polymorphism was found to be related to object response rate (ORR) in mCRC patients whose tumors had KRASwt. The 12 KRASwt patients harboring at least a variant G allele (TG or GG) had a 42% ORR compared with a 9% ORR in 55 KRASwt patients with let-7 lcs6 TT genotype (P = 0.02, Fisher's exact test). KRASwt patients with TG/GG genotypes had trend of longer median progression-free survival (3.9 versus 1.3 months) and OS (10.7 versus 6.4 months) compared to those with TT genotypes. CONCLUSIONS: these results are the first to indicate that the KRAS 3'UTR polymorphism may predict for cetuximab responsiveness in KRASwt mCRC patients, which warrants validation in other clinical trials.

Evidence for a multidimensional self-efficacy for exercise scale.

This series of three studies considers the multidimensionality of exercise self-efficacy by examining the psychometric characteristics of an instrument designed to assess three behavioral subdomains: task, scheduling, and coping. In Study 1, exploratory factor analysis revealed the expected factor structure in a sample of 395 students. Confirmatory factor analysis (CFA) confirmed these results in a second sample of 282 students. In Study 2, the generalizability of the factor structure was confirmed with CFA in a randomly selected sample of 470 community adults, and discriminant validity was supported by theoretically consistent distinctions among exercisers and nonexercisers. In Study 3, change in self-efficacy in conjunction with adoption of novel exercise was examined in a sample of 58 women over 12 weeks. Observed changes in the three self-efficacy domains appeared to be relatively independent. Together, the three studies support a multidimensional conceptualization of exercise self-efficacy that can be assessed and appears to be sensitive to change in exercise behavior.

Case report of a 13-year-old struck by lightning.

Lightning strikes kill 1,000 people per year worldwide. Cardiac arrests resulting from lightning strikes have good survival rates but there is a significant degree of morbidity amongst the survivors. This is the case report of a 13-year-old boy who had a cardiac arrest following a direct lightning strike, and his subsequent management.

A policy analysis of the Expert Patient in the United Kingdom: self-care as an expression of pastoral power?

The rise in chronic illness and comorbidity in Western society has resulted in an increasing emphasis on self-care initiatives. In the United Kingdom this is exemplified by the Expert Patient policy. This paper discusses the Expert Patient initiative as an example of the State's third way approach to public health. The extent to which this policy challenges conventional power relationships between professional and patient, and fosters equal partnership is examined. In particular, how expert is defined and whether a professional understanding of the term is reconcilable with a patient's expertise is debated. The paper argues that the Expert Patient initiative is unlikely to reconstruct chronic illness and may further complicate the State's responsibility in meeting the needs of those with chronic illness. Issues of power within self-care are explored to illuminate the policy, and this paper argues that the Expert Patient initiative is an example of Foucault's notion of pastoral power. Although the Expert Patient policy focuses on the rights and responsibilities of those with chronic illness, this paper concludes that there is no corresponding strategy to challenge professionals' assumptions toward those with chronic illness.

Systematic review of water fluoridation.

OBJECTIVE: To review the safety and efficacy of fluoridation of drinking water. DESIGN: Search of 25 electronic databases and world wide web. Relevant journals hand searched; further information requested from authors. Inclusion criteria were a predefined hierarchy of evidence and objectives. Study validity was assessed with checklists. Two reviewers independently screened sources, extracted data, and assessed validity. MAIN OUTCOME MEASURES: Decayed, missing, and filled primary/permanent teeth. Proportion of children without caries. Measure of effect was the difference in change in prevalence of caries from baseline to final examination in fluoridated compared with control areas. For potential adverse effects, all outcomes reported were used. RESULTS: 214 studies were included. The quality of studies was low to moderate. Water fluoridation was associated with an increased proportion of children without caries and a reduction in the number of teeth affected by caries. The range (median) of mean differences in the proportion of children without caries was -5.0% to 64% (14.6%). The range (median) of mean change in decayed, missing, and filled primary/permanent teeth was 0.5 to 4.4 (2.25) teeth. A dose-dependent increase in dental fluorosis was found. At a fluoride level of 1 ppm an estimated 12.5% (95% confidence interval 7.0% to 21.5%) of exposed people would have fluorosis that they would find aesthetically concerning. CONCLUSIONS: The evidence of a beneficial reduction in caries should be considered together with the increased prevalence of dental fluorosis. There was no clear evidence of other potential adverse effects.

The sensitivity to change over time of the Bristol Activities of Daily Living Scale in Alzheimer's disease.

Activities of daily living scales can be a useful tool in assessing change in people with dementia, either as the disease progresses or in response to treatment. However, little data exist as to the sensitivity to change of instruments used. The Bristol Activities of Daily Living Scale was developed with assistance from the carers of community dwelling people with dementia to be completed by such people and has been shown to have internal consistency as well as face and construct validity. This study aimed to analyse the sensitivity to change of the Bristol Activities of Daily Living Scale in people with Alzheimer's disease receiving anticholinesterase medication. Using the Clinician's Global Rating of Change as a gold standard for change, differences between Bristol Activities of Daily Living Scale scores before and after medication were compared with change in Mini-Mental State Examination, Alzheimer's Disease Assessment Scale - Cognitive and the Nurses Observation Scale for Geriatric Patients, in 61 older adults receiving anticholinesterase medication for Alzheimer's disease. Both the Bristol Activities of Daily Living Scale and the Nurses Observation Scale for Geriatric Patients are sensitive and specific in predicting improvement or stability as measured by the clinician's global rating of change. However, unlike the Nurses Observation Scale for Geriatric Patients, change over time in the Bristol Activities of Daily Living Scale significantly correlates with change in the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale - Cognitive. The Bristol Activities of Daily Living Scale is sensitive to change in activities of daily living and shows the expected and desirable relationship with measures of cognition.

Extrahepatic synthesis of plasminogen in the human cornea is up-regulated by interleukins-1alpha and -1beta.

The avascular cornea has limited access to plasma proteins, including plasminogen, a protein that is synthesized by the liver and supplied to most tissues via the blood. Recent experiments by others using plasminogen-deficient mice revealed the importance of plasmin, the active form of plasminogen, for the maintenance of the normal cornea and for corneal wound healing [Kao, Kao, Bugge, Kaufman, Kombrinck, Converse, Good and Degan (1998) Invest. Ophthalmol. Vis. Sci. 39, 502-508; Drew, Kaufman, Kombrinck, Danton, Daugherty, Degen and Bugge (1998) Blood 91, 1616-1624]. In the present experiments, plasmin was identified as a major serine proteinase in the human cornea. The major plasminogen and plasmin forms on non-reducing zymograms and Western blots had Mr values of 76x10(3) and 85x10(3), with minor forms of Mr 200x10(3), 135x10(3), 68x10(3) and 45x10(3). Angiostatin-like peptides with Mrs of 48x10(3), 45x10(3) and 38x10(3) were observed which bound to lysine-Sepharose and reacted with anti-plasminogen monoclonal antibodies directed towards kringle domains 1-3 of plasminogen. The cornea contained 1.1+/-0.15 microgram of plasminogen+plasmin/cornea, or 0.54+/-0.05 microgram of plasminogen+plasmin/mg of protein. Cornea conditioned medium contained nine times the amount of plasminogen+plasmin that could be extracted from the cornea. These data suggested that corneal cells, unlike most extrahepatic cells, synthesize plasminogen. The synthesis of plasminogen by the cornea was confirmed by immunoprecipitation of metabolically labelled plasminogen, sequencing of its cDNA obtained by reverse transcriptase-PCR and inhibition of protein synthesis. Interleukins-1alpha and -1beta stimulated corneal plasminogen synthesis 2-3-fold; however, interleukin-6 decreased corneal plasminogen synthesis by approx. 40% at early times after addition of the cytokine. By 24 h of culture, no differences were noted in the presence and absence of interleukin-6. Thus the cornea can synthesize plasminogen and regulate its synthesis in response to its environment, including cytokines induced in the cornea by injury and inflammation. Therefore the cornea can control the amount of plasminogen, the precursor of both plasmin and angiostatin.

Optimization of single-cell gel electrophoresis (SCGE) for quantitative analysis of neuronal DNA damage.

Neuronal death can be induced by DNA-damaging agents and occurs by apoptosis involving a specific signal-transduction pathway. However, to our knowledge, methods for the quantitative determination of DNA damage in individual neurons have not yet been described. Here we optimize the single-cell gel electrophoresis (SCGE) or "comet"-assay to measure DNA damage within individual neurons growing in dissociated cell culture. In addition, we have written a macro for the NIH Image program to determine the tail moment of individual comets. We have calibrated this method using gamma-irradiated (0-16 Gy) cerebral cortical neurons from the rat central nervous system. Neuronal DNA damage (in the form of DNA strand breaks) occurs in a linear, dose-dependent manner, which can be quantitatively determined in vitro using the SCGE assay. These data demonstrate that the SCGE assay is an effective method to measure DNA damage in individual neurons and may be highly useful for the study of neuronal DNA damage formation, repair and apoptosis.

Haemophilus influenzae type b polysaccharides-protein conjugate vaccine elicits a more diverse antibody repertoire in infants than in adults.

Conjugation of bacterial polysaccharides (PS) to protein carriers confers the ability to elicit protective serum Ab in infants, who respond poorly to plain PS. The serum Ab of young children immunized with Haemophilus influenzae type b (Hib) PS conjugate vaccine varies with age and Ag formulation. To understand these age-related changes in human anti-Hib PS immune responses we determined the variable region gene sequences encoding anti-Hib PS mAbs of infants immunized with Hib oligosaccharide-diphtheria toxin vaccine. The anti-Hib PS repertoire of children differs from that of adults. A smaller proportion of mAbs from children have high affinity for Hib PS, and the overall variable region gene repertoire of infants is more diverse than that in adults. Variable region genes encoding high affinity mAbs of infants are similar to the restricted repertoire described in adults. Low affinity anti-Hib PS mAbs of infants are encoded by a heterogeneous group of genes that are uncommonly observed in the adult repertoire. Abs with high affinity for Hib PS from infants, like most mAbs from adults, react only with Hib PS and the structurally similar PS of Escherichia coli K100, whereas low affinity mAbs of infants are polyreactive. The low affinity anti-Hib PS mAbs of infants immunized with Hib oligosaccharide-diphtheria toxin vaccine vaccine are not reflected in serum Ab. However, the differences between the variable region gene repertoires of adults and infants may account for the distinct immunologic characteristics of the anti-Hib PS responses in young children immunized with other vaccine formulations.

Neurogenesis in septum, amygdala and hippocampus in the marsupial brushtailed possum (Trichosurus vulpecula).

The times of origin of neurons in the septum, amygdala and hippocampus of the marsupial brushtailed possum, Trichosurus vulpecula, were determined with 3H thymidine autoradiography. The long time period for neurogenesis in the brushtailed possum facilitated analysis of neurogenetic gradients in the brain. A series of 20 possums were injected with 3H thymidine from postnatal (P) days 5-95 and were allowed to survive until brain cytoarchitecture was mature. Our results indicate that septal neurogenesis was complete by P21 (38 days after conception) with a medial to lateral gradient of neurogenesis evident in the lateral septal division. Neurogenesis in the amygdala was complete in the basal, central and medial amygdaloid nuclei by P21, and in the lateral amygdaloid nucleus by P46, with a medial to lateral gradient of neurogenesis evident in basal, central and lateral amygdaloid nuclei. In the hippocampus, neurogenesis of pyramidal cells was complete in field CA3 by P50, and in field CA1 by P55. Early forming pyramidal cells (P5-12) were distributed adjacent to the stratum oriens in fields CA1 and CA3, with later forming pyramidal cells distributing in the middle of the stratum pyramidale (P21-32) and on the edge adjacent to the stratum radiatum (P46). Neurogenesis of dentate granule cells extended over a long period of time, from P5, at least until P82, with the earliest forming granule cells (P5-12) distributed adjacent to the stratum moleculare, and the latest forming granule cells (P82) adjacent to the hilus.

Vitamin A deficiency alters rat neutrophil function.

Previous studies showed a higher percentage of neutrophils from vitamin A deficient rats are hypersegmented and contain lower levels of cathepsin G than the neutrophils from control rats. In this study chemotaxis, phagocytosis and oxidant generation were studied using either isolated neutrophils or neutrophils in whole blood from four dietary groups of rats: 1) vitamin A deficient rats; 2) vitamin A deficient rats that received vitamin A for 16, 8, 4 or 2 d prior to killing; 3) weight-matched rats pair-fed a vitamin A-complete diet; and 4) rats fed nonrestricted, vitamin A complete diet. Chemotaxis towards P. aeruginosa conditioned medium and formylated methinyl leucinyl phenylalanine was significantly lower for neutrophils from vitamin A-deficient rats than for neutrophils from weight-matched pair-fed rats, nonrestricted vitamin A sufficient rats and vitamin A deficient rats that received vitamin A for 16 d prior to killing. No differences in chemotaxis towards activated rat serum were noted among the neutrophils from the four groups of rats. Adhesion of P. aeruginosa organisms, phagocytosis of these organisms and generation of active oxidative molecules were significantly lower in the neutrophils from the vitamin A-deficient rats relative to these functions in the neutrophils from the vitamin A deficient rats that received vitamin A for 16 d, weight-matched rats pair-fed a vitamin A complete diet; and rats fed nonrestricted, vitamin A-complete diet. Eight days after vitamin A administration to vitamin A deficient rats, the ability of the neutrophils to phagocytose P. aeruginosa organisms and to generate active oxidant molecules was restored to the levels observed for weight-matched, pair-fed rats and rats fed nonrestricted, vitamin A complete diet. The elucidated alterations in neutrophil function in vitamin A deficient rats probably contribute to the altered ability of vitamin A deficient rats to fight infections.