Structure and membrane affinity of a suite of amphiphilic siderophores produced by a marine bacterium

Iron concentrations in the ocean are low enough to limit the growth of marine microorganisms, which raises questions about the molecular mechanisms these organisms use to acquire iron. Marine bacteria have been shown to produce siderophores to facilitate iron(III) uptake. We describe the structures of a suite of amphiphilic siderophores, named the amphibactins, which are produced by a nearshore isolate, gamma Proteobacterium, Vibrio sp. R-10. Each amphibactin has the same Tris-hydroxamate-containing peptidic headgroup composed of three ornithine residues and one serine residue but differs in the acyl appendage, which ranges from C-14 to C-18 and varies in the degree of saturation and hydroxylation. Although amphiphilic siderophores are relatively rare, cell-associated amphiphilic siderophores are even less common. We find that the amphibactins are cell-associated siderophores. As a result of the variation in the nature of the fatty acid appendage and the cellular location of the amphibactins, the membrane partitioning of these siderophores was investigated. The physiological mixture of amphibactins had a range of membrane affinities (3.8 x 10(3) to 8.3 x 10(2) M(-1)) that are larger overall than other amphiphilic siderophores, likely accounting for their cell association. This cell association is likely an important defense against siderophore diffusion in the oceanic environment. The phylogenetic affiliation of Vibrio sp. R-10 is discussed, as well as the observed predominance of amphiphilic siderophores produced by marine bacteria in contrast to those produced by terrestrial bacteria.     

Localized epidermolytic hyperkeratosis of the female external genitalia

BACKGROUND: Epidermolytic hyperkeratosis (EH) is most commonly associated with the diffuse involvement of congenital ichthyosiform erythroderma, but can also be found in a localized pattern. Localized EH is rare, but mucocutaneous lesions have been been identified, most commonly in the mouth. METHODS: We observed a 58-year-old African-American female who noted spots on her genitalia for approximately 2 years. The lesions were increasing in size, darkening, and had become pruritic and sore over the past 6 months. RESULTS: Physical examination revealed seven scattered, tan to brown, verrucoid papules on the labia and mons pubis, resembling condylomata acuminata or Bowenoid papulosis. Biopsy of a single labial papule revealed epidermal acanthosis, compact hyperkeratotic papillomatosis, perinuclear clear zones, granular keratohyalin clumping, hypergranulosis, and dyskeratosis resulting in intracellular eosinophilic globules, all characteristic of EH. CONCLUSIONS: Because of the rarity of localized genital EH and similar appearance to common diagnoses, clinical confusion may occur without biopsy.     

Mortality risks associated with pediatric dental care using general anesthesia in a hospital setting

The purpose of the present study was to the review the literature and survey the risk of mortality associated with general anesthesia in children in a hospital setting. An 8-item, one page, survey was sent to all (928) southeast regional hospital members of the American Hospital Association (AHA). A response rate of 41% was established. They reported 22,615 dental cases using general anesthesia on children the ages 1 to 6 years and there were no deaths associated with anesthesia reported by responding hospitals. It was concluded that no deaths were reported among more than 22,000 cases over a 10-year period. This provides valuable information on the safety using general anesthesia for pediatric dental care.     

A half century of longitudinal methods in social gerontology: evidence of change in the journal

OBJECTIVES: With a focus on the use of longitudinal data, this study reviews trends in the quantitative analysis of social science data on aging during the past half century. METHODS: A content analysis was performed on 227 articles from 12 volumes that were systematically sampled from the Journal of Gerontology: Social Sciences to examine change in the type of data and quantitative methods used (1946-2000). RESULTS: Cross-sectional analysis remains the single most frequent type of study, but the publication of analyses based on longitudinal panel data increased appreciably over the five decades studied. There was little increase in the use of repeated cross-sectional analysis. DISCUSSION: Despite the widespread use of cross-sectional analysis, interest in data with more than one occasion of measurement has grown among social scientists who are reviewing for and publishing in the JOURNAL. Given the longitudinal data now available, social science research on aging should give more explicit attention to three issues: attrition, change in repeated measures of independent variables, and models to account for many waves of data.     

Age-associated sex differences in response to food deprivation in two animal tests of anxiety

The effects of mild food deprivation (7 days of food restricted to once daily feeding to maintain body weights at 85% of free-feeding weights) were examined in adult male and female and adolescent female rats tested in the elevated plus maze and social interaction tests of anxiety. In adult male rats, food deprivation appeared to have an anxiolytic effect in the plus-maze as it significantly increased the percentage of entries onto open arms and the percentage of time spent on the open arms, without changing the number of closed arm entries. There were no effects of food deprivation in adult females, although in adolescent females food deprivation significantly increased the percentage of open arm entries rats. Adolescent female rats have female brains, but do not have circulating gonadal hormones and thus these results suggest that circulating female gonadal hormones are able to suppress some of the effects of mild food deprivation in the plus-maze. In the social interaction test, there were no effects of food deprivation in any group on the time spent in social interaction. There were opposite effects on locomotor activity in the adult male and female rats, with deprivation increasing activity in males and decreasing it in females. There were no effects of food deprivation on locomotor activity in the adolescent females, suggesting that circulating gonadal hormones were responsible for the bidirectional effects in the adult rats. In both tests there were age-associated differences in the female rats, with the adolescent females being less anxious (higher percentage of open arm entries and increased social interaction) than the adults.     

Distinct response of experimental neuroblastoma to combination antiangiogenic strategies

Background: The authors have shown previously that experimental neuroblastoma is partially inhibited (48%) by antivascular endothelial growth factor (anti-VEGF) antibody. The topoisomerase-I inhibitor, topotecan, has been shown to have antiangiogenic activity when administered in a low-dose, high-frequency regimen. We hypothesized that combining topotecan with anti-VEGF would suppress neuroblastoma more effectively than either agent alone. Methods: A total of 10⁶ neuroblastoma cells were implanted intrarenally in athymic mice. Animals received vehicle, topotecan, anti-VEGF, or topotecan plus anti-VEGF (n = 9, 20, 20, 20, respectively). All control and half the treated mice were killed at 6 weeks. Remaining (rebound) mice were maintained without treatment for 3 more weeks. Patterns of vasculature and apoptosis were determined immunohistochemically. Results: Tumor weights at 6 weeks were reduced significantly in topotecan-only (0.07g) and combination-treated animals (0.08 g), compared with controls or anti-VEGF[ndash ]treated mice (1.18 g, 0.53 g; P [lt ] .0007, all). At 9 weeks, rebound tumor weights were greatest in anti-VEGF (2.82 g), intermediate in topotecan (1.82 g), and least in combination-treated animals (1.47 g); however, the only significant difference was between anti-VEGF and combination therapy (P = 0.04). All treated tumors were vascularized sparsely in comparison with controls at 6 weeks, but exhibited brisk neoangiogenesis at 9 weeks. Conclusions: Topotecan either with or without anti-VEGF antibody significantly suppresses neuroblastoma xenograft growth in comparison with controls or anti-VEGF antibody alone. Combining topotecan with anti-VEGF antibody significantly inhibited rebound tumor growth in comparison with anti-VEGF antibody alone. Combination therapy may improve durability of antiangiogenic inhibition of neuroblastoma.     

Cadaveric-donor organ recovery at a hospital-independent facility

BACKGROUND: Of the many logistic issues addressed throughout the cadaveric organ donation process, timely access to the operating theater for surgical recovery of organs and tissues can be one of the most problematic. Delay in recovery adds to cost, risks organ viability, and compounds donor family anguish with compromise to donation consent. METHODS: From March 1 to November 30, 2001, 25 cadaveric donors were selected and successfully transferred from local donor critical care units to an off-site facility, which was constructed, equipped, and staffed to allow surgical recovery of organs and tissues. Assessment of the recovery process and outcome results was compared to 42 consecutive, hospital-based, organ recoveries within the Mid-American Transplant Services (MTS) organ procurement organization region. RESULTS: Twenty-five MTS-facility and 42 hospital organ recoveries were successfully conducted with no technical losses and satisfactory function in all 206 transplanted organs. From the MTS donor group, 7 hearts, 4 lungs, 21 livers, 28 kidneys, and 5 pancreases were successfully transplanted. Statistically significant in the MTS group was higher donor age (44.1 vs. 30.2 years), shorter total donor management time (539 vs. 718 min), reduced delay in start of surgery (25 vs. 77 min), shorter cold ischemia time for recovered pancreases (355 vs. 630 min), and reduced mean cost per donor ($10,636 vs. $12,918). There was no significant difference in race, gender, cause of death, vasopressor requirements, organs per donor recovered (3.12 vs. 3.62) or transplanted (2.60 vs. 3.36), rate of tissue recoveries (68% vs. 67%), total operating room time (207 vs. 200 min.), or cold ischemia time (excluding pancreas). CONCLUSIONS: Cadaveric-donor multiorgan and tissue recovery at this hospital-independent facility was successfully accomplished in a manner indistinguishable from conventional hospital organ and tissue recovery. The intended objectives of improved access to the operating theater were realized along with the added benefit of significant cost savings and convenience to hospital personnel and surgical recovery teams.