Overexpression of CDC25B and LAMC2 mRNA and protein in esophageal squamous cell carcinomas and premalignant lesions in subjects from a high-risk population in China.

Molecular events associated with the initiation and progression of esophageal squamous cell carcinoma (ESCC) remain poorly understood but likely hold the key to effective early detection approaches for this almost invariably fatal cancer. CDC25B and LAMC2 are two promising early detection candidates emerging from new molecular studies of ESCC. To further elucidate the role of these two genes in esophageal carcinogenesis, we did a series of studies to (a) confirm RNA overexpression, (b) establish the prevalence of protein overexpression, (c) relate protein overexpression to survival, and (d) explore their potential as early detection biomarkers. Results of these studies indicated that CDC25B mRNA was overexpressed (>/=2-fold overexpression in tumor compared with normal) in 64% of the 73 ESCC cases evaluated, whereas LAMC2 mRNA was overexpressed in 89% of cases. CDC25B protein expression was categorized as positive in 59% (144 of 243) of ESCC cases on a tumor tissue microarray, and nonnegative LAMC2 patterns of protein expression were observed in 82% (225 of 275) of cases. Multivariate-adjusted proportional hazard regression models showed no association between CDC25B protein expression score and risk of death [hazard ratio (HR) for each unit increase in expression score, 1.00; P = 0.90]; however, several of the LAMC2 protein expression patterns strongly predicted survival. Using the cytoplasmic pattern as the reference (the pattern with the lowest mortality), cases with a diffuse pattern had a 254% increased risk of death (HR, 3.52; P = 0.007), cases with no LAMC2 expression had a 169% increased risk of death (HR, 2.69; P = 0.009), and cases with a peripheral pattern had a 130% greater risk of death (HR, 2.30; P = 0.02). CDC25B protein expression scores in subjects with esophageal biopsies diagnosed as normal (n = 35), dysplastic (n = 23), or ESCC (n = 32) increased significantly with morphologic progression. For LAMC2, all normal and dysplastic patients had a continuous pattern of protein expression, whereas all ESCCs showed alternative, noncontinuous patterns. This series of studies showed that both CDC25B and LAMC2 overexpress RNA and protein in a significant majority of ESCC cases. The strong relation of LAMC2 pattern of protein expression to survival suggests a role in prognosis, whereas the association of CDC25B with morphologic progression indicates a potential role as an early detection marker.     

Comparison of clinical efficacy and safety of three professional at-home tooth whitening systems

A three-cell, randomized, parallel, investigator-blinded clinical trial was conducted to compare the efficacy and safety of three professional at-home tooth whitening systems, including Crest Professional Whitestrips (6.5% H2O2), Day White 2 (7.5% H2O2) and Nite White Excel 2 (16% carbamide peroxide equivalent). Ninety subjects were randomly assigned to three groups (30/group). Subjects were instructed to use the assigned whitener following the manufacturers' instructions. Clinical examinations at baseline, and on days 3, 7, 14, and 18 (Day White), or 21 (Crest Professional Whitestrips and Nite White) included the following parameters: 1) oral tissues; 2) tooth shade by the Vitapan Classical shade guide; 3) tooth shade by a chromameter with a jig; and, 4) tooth sensitivity and gingival irritation. The results showed significant shade reductions with time in all three groups. Nite White resulted in significantly greater shade reductions in periods between days 7, 14, or 21 and baseline than did the other two systems. Tooth sensitivity and gingival irritation, which were mostly mild and transient, occurred in all groups. It is concluded that all three whitening systems evaluated are effective and safe. Nite White Excel is superior to the other two systems because it provides a greater whitening efficacy with comparable or lower incidence of tooth sensitivity and gingival irritation.     

Sex steroids do not affect shigatoxin cytotoxicity on human renal tubular or glomerular cells

Background

The greater susceptibility of children to renal injury in post-diarrheal hemolytic-uremic syndrome (HUS) may be related, at least in part, to heightened renal cell sensitivity to the cytotoxic effect of Shiga toxin (Stx), the putative mediator of kidney damage in HUS. We hypothesized that sexual maturation, which coincides with a falling incidence of HUS, may induce a relatively Stx-resistant state in the renal cells.

Methods

Cultured human glomerular endothelial (HGEN), human glomerular visceral epithelial (HGEC) and human proximal tubule (HPT) cells were exposed to Stx-1 after pre-incubation with progesterone, β-estradiol or testosterone followed by determination of cytotoxicity.

Results

Under basal conditions, Stx-1 potently and dose-dependently killed HPT and HGEC, but had relatively little effect on HGEN. Pre-incubation for 1, 2 or 7 days with physiologic or pharmacologic concentrations of progesterone, β-estradiol or testosterone had no effect on Stx-1 cytotoxicity dose-response on any cell type. In addition, no steroid altered Gb3 expression (Stx receptor) by any cell type at any time point.

Conclusion

These data do not support the notion that hormonal changes associated with puberty induce an Stx-resistant state within kidney cells.     

Entry of inflammatory cells into the mouse vagina following application of candidate microbicides: comparison of detergent-based and sulfated polymer-based agents

BACKGROUND: Because topical microbicides designed to prevent the spread of sexually transmitted diseases may be applied frequently, it is important to ensure product safety as well as efficacy. A murine model was developed to test for induction of inflammatory responses following application of candidate microbicides. GOAL: A comparison was made of the induction of inflammation following vaginal application of detergent-based and sulfated polymer-based microbicides. STUDY DESIGN: Vaginal leukocytes were collected, identified, and quantified following microbicide application to detect the entry of inflammatory leukocytes into the vaginal lumen. RESULTS: Large numbers of neutrophils and macrophages entered the vaginal lumen following a single application of detergent-based microbicides. No significant increase in vaginal leukocytes was detected following a single or repeated application of sulfated polymer-based microbicides. CONCLUSION: Application of sulfated polymer-based microbicides was less likely to result in inflammatory responses than was application of detergent-based compounds. This murine model should prove useful as part of a screening process to prioritize candidate microbicides before clinical trial.     

Sharps injury recordkeeping activities and safety product use in California health care facilities: pilot study results from the sharps injury control program

BACKGROUND: In 1999, licensed health care facilities in California (N = 2532) were invited to participate in a survey about occupational bloodborne pathogens exposure surveillance activities, recordkeeping methods, and use of safety-enhanced sharps devices. RESULTS: A total of 1274 facilities responded to the survey from January 1999 through August 1999 (response rate = 50%). Sharps-related injuries were recorded for multiple departments on various forms in diverse manners. Only 66% of hospitals, 37% of home health agencies, and 33% of skilled nursing facilities reported sharps injuries on a mandated sharps injury log. More than 70% of facilities stated that they used some type of safety device or needleless system, but this figure varied by type of device and facility type. Eighty-four percent of general acute care hospitals, 28% of home health agencies and skilled nursing facilities each had evaluated at least 1 safety-enhanced device. Almost 90% of all facilities expressed a need for educational materials on topics such as device selection and evaluation. CONCLUSIONS: Standardization of surveillance and recordkeeping activities does not exist across facility types. Standards and regulations demand complex recordkeeping activities. Increased funding for distribution of educational materials and on-site training should accompany changes in mandated reporting activities when appropriate. Increased testing and evaluation of devices across facility types are necessary to ensure that safety-enhanced devices are protective of health care workers and patients.     

Imaging of acute head injury

This article reviews the neuroradiological evaluation of acute head injury with an emphasis on CT and MR imaging. Subacute and chronic head injury are not discussed. CT remains the modality of choice in the emergency setting, permitting rapid, comprehensive assessment of the great majority of head injuries. MR is most useful in patients in whom there is a discrepancy between clinical symptoms and CT findings. In addition, MR is the imaging modality of choice in the subacute and chronic setting. The superior contrast resolution of MR permits optimal evaluation of nonhemorrhagic (and hemorrhagic) white matter shearing injuries, and the lack of beam-hardening artifact permits a more thorough evaluation of the brain stem, posterior fossa, and cortical surface.     

Comparison of Likelihood Approaches for Combined Segregation and Linkage Analysis of a Complex Disease and a Candidate Gene Marker Under Different Ascertainment Schemes

We compared two joint likelihood approaches, with complete (L1) or without (L2) linkage disequilibrium, under different ascertainment schemes, for the genetic analysis of the disease trait and marker gene 1 in replicate 42. Joint likelihoods were computed without a correction for the selection scheme. For the different sampling schemes we have explored, our results suggest that L1 is a more powerful approach than L2 to detect major gene and covariatc effects as well as to identify accurately gene×covariate interaction effects in a common and complex disease such as the Genetic Analysis Workshop 12 MG6 simulated trait. © 2001 Wiley‐Liss, Inc.     

Incidence of and risk factors for acute stress disorder in children with injuries

BACKGROUND: To assess the incidence of and risk factors for Acute Stress Disorder (ASD) in children with injuries. Numerous studies have documented the increased incidence of PTSD in those initially diagnosed with ASD. PTSD symptoms cause tremendous morbidity and may persist for many years in some children. METHODS: Children hospitalized with one or more injuries were interviewed and assessed with the following: Child Stress Disorders Checklist (CSDC), Family Strains Scale, Brief Symptom Inventory (BSI) and Facial Pain Scale. RESULTS: Participants included sixty-five children (ages 7-18 years). The mechanisms of injury varied (e.g. MVC, penetrating). The mean injury severity score was 8.9 +/- 7. The mean length of hospital stay was 4.6 +/- 4.6 days. Altogether, 18 (27.7%) of participants met DSM IV criteria for ASD during their acute hospital stay. Risk factors such as level of family stress, caregiver stress, child's experience of pain, and child's age were predictive of acute stress symptoms. CONCLUSION: We have identified four risk factors of ASD that have implications for the treatment, and possibly, preventative intervention for PTSD. Further investigation and greater understanding of risk factors for ASD in children with injuries may facilitate the design of acute interventions to prevent the long-term negative outcomes of traumatic events.     

Predictors of contraception knowledge and use among postpartum adolescents in El Salvador

OBJECTIVE: This study was undertaken to describe demographics and contraceptive familiarity and use among postpartum adolescents in El Salvador. STUDY DESIGN: Questionnaire-guided interviews were conducted in Spanish with 50 postpartum adolescents at an urban, public hospital in El Salvador. Open-ended questions included assessments of education, partnership status, and contraceptive knowledge and use patterns. RESULTS: The median age of subjects was 17 years, 84% were nulliparous, 80% had partners, and 6% were married. Eighty-four percent of the women reported contraception knowledge and 18% reported contraception use. Educational experience and literacy predicted contraceptive knowledge (P = .008 and .001, respectively), but not use. After delivery and postpartum contraception education, 58% of the subjects stated intention to use contraception. Having a partner and living with him were predictors of intent to use contraception (P = .001 and .002, respectively). Being single negatively predicted intention to use contraception (P = .001). CONCLUSION: Education and literacy predicted contraceptive knowledge; however, contraceptive knowledge did not predict contraceptive use. Adolescent contraception use depends on more than just contraceptive knowledge.     

Regulation of a Bacillus subtilis mobile genetic element by intercellular signaling and the global DNA damage response

Horizontal gene transfer contributes to the evolution of bacterial species. Mobile genetic elements play an important role in horizontal gene transfer, and characterization of the regulation of these elements should provide insight into conditions that influence bacterial evolution. We characterized a mobile genetic element, ICEBs1, in the Gram-positive bacterium Bacillus subtilis and found that it is a functional integrative and conjugative element (ICE) capable of transferring to Bacillus and Listeria species. We identified two conditions that promote ICEBs1 transfer: conditions that induce the global DNA damage response and crowding by potential recipients that lack ICEBs1. Transfer of ICEBs1 into cells that already contain the element is inhibited by an intercellular signaling peptide encoded by ICEBs1. The dual regulation of ICEBs1 allows for passive propagation in the host cell until either the potential mating partners lacking ICEBs1 are present or the host cell is in distress.