Enhanced responses to a DNA vaccine encoding a fusion antigen that is directed to sites of immune induction

Viral infection and vaccination with DNA both induce similar immune responses to encoded antigens that are produced by the host. The availability of antigens in lymphoid organs is important in generating an immune response to viral challenge. Antigen availability may also be important in the response to DNA vaccines, because immune responses are stronger when antigen is secreted from DNA-transfected cells. We directed antigen to lymphoid organs by vaccination with DNA encoding antigen-ligand fusion proteins. The two ligands examined bind to receptors that are present on high endothelial venule cells of lymph nodes or on antigen-presenting cells. Here we show that both the humoral and the cellular immune responses to a model DNA vaccine were enhanced using either antigen-targeting strategy. Moreover, directing antigen to antigen-presenting cells speeded up, and altered the form of, the immune response. Directing antigen to sites of immune-response induction may represent a generic means of tailoring a potent and effective immune response to a DNA vaccine.     

osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification

Osteoprotegerin (OPG) is a secreted protein that inhibits osteoclast formation. In this study the physiological role of OPG is investigated by generating OPG-deficient mice. Adolescent and adult OPG-/- mice exhibit a decrease in total bone density characterized by severe trabecular and cortical bone porosity, marked thinning of the parietal bones of the skull, and a high incidence of fractures. These findings demonstrate that OPG is a critical regulator of postnatal bone mass. Unexpectedly, OPG-deficient mice also exhibit medial calcification of the aorta and renal arteries, suggesting that regulation of OPG, its signaling pathway, or its ligand(s) may play a role in the long observed association between osteoporosis and vascular calcification.     

Geographical variation in the referral of patients with chronic end stage renal failure for renal replacement therapy

The translocation of t(8;16)(p11;p13) has been demonstrated in the blasts of a phenotypically normal newborn baby with acute monoblastic leukemia. No antileukemic therapy was administered and spontaneous, complete remission was observed at 2 months of age. The patient remains well 18 months after the diagnosis and continues to have a normal hemogram.     

Strategies to manipulate reliability: impact on statistical associations

OBJECTIVE: To examine the effects of improving measurement reliability on associations between risk factors and childhood psychiatric disorder. METHOD: Data were from a general population sample of parents (N = 211) with children aged 6 to 16 years. Reliability of measurement was improved in three ways: by increasing the number of items in a scale (internal-consistency reliability), by averaging assessments of the same variables collected on two different occasions, and by constructing latent variable measures. To assess the effects of improving reliability, selected risk factors were regressed on parental assessments of childhood oppositional defiant disorder (ODD) and overanxious disorder (OAD). RESULTS: Improving reliability led to systematic increases in the magnitude of standardized regression coefficients between family dysfunction and ODD (beta = .30-.51) and between family dysfunction and OAD (beta = .24-.48). In multiple regression, improving reliability served to strengthen the specificity of associations between ODD, OAD, and family dysfunction and maternal depressed mood. Although latent variable methods produced the largest associations, the standard errors of these estimates were also larger, resulting in wider confidence intervals and slightly larger significance values. CONCLUSIONS: Improving reliability of measurement results in larger associations between risk factors and childhood disorder and may increase the opportunity of revealing differential associations between variables.     

Familial aggregation of emotional and behavioral problems of childhood in the general population

OBJECTIVE: This study sought to evaluate the existence and implications of familial aggregation of emotional and behavioral problems of childhood in a general population sample. METHOD: The children included in the study were chosen with the use of a sampling technique that identified households in which there were two or more children aged 4-16 years living at home at the time of the survey. Ratings on checklists of emotional and behavioral problems were obtained from parents, teachers of children in elementary school, and the children themselves if they were adolescents aged 12-16. Children were classified as having problems if their scores on scales of conduct, attention deficit, or emotional problems were in the top 10% of the distribution of scores from any informant. RESULTS: There was evidence for familial aggregation of these problems, particularly conduct and emotional problems. However, this was largely derived from the parents' reports of symptoms, not the teachers' or adolescents' reports. The degree of familial aggregation varied according to certain sibship characteristics and patterns of comorbidity. CONCLUSIONS: Familial aggregation of emotional and behavioral problems does exist in a community population and is not simply an artifact of clinic attendance.     

Injury prevention strategies to promote helmet use decrease severe head injuries at a level I trauma center

Head injuries (HIs) remain a major contributor to trauma mortality, with many deaths occurring despite optimal use of available therapy. Injury prevention is vital to decrease the impact of HIs. Helmets can decrease the severity of HIs in both bicycle crashes (BCs) and motorcycle crashes (MCCs). A major challenge is to increase helmet use. A mandatory motorcycle helmet law in 1990 and information campaigns aimed at bicyclists have increased the percentage of riders wearing helmets in Washington State. We hypothesized that there would be an associated decrease in the proportion of severe HIs in BC and MCC admissions to the state's only level I trauma center. We analyzed injury region and outcomes for all 466 BC and 992 MCC instate admissions from 1986 to 1993. For BCs, the proportion of severe HIs (Abbreviated Injury Scale score of 4 or 5) declined from 29% in 1986 to 11% in 1993 (p = 0.02). BC trends paralleled helmet use in observations on 8,860 bicycle riders in the area, in which the percentage of helmeted riders rose from 5% in 1987 to 62% in 1993 (p < 0.001). For MCCs, severe HIs declined from 20% before passage of the helmet law to 9% afterward (p < 0.001). Mortality decreased for BCs and MCCs (p < 0.05), and length of hospital stay and ICU stay decreased for BCs (p < 0.05). The percentage of helmeted BC admissions rose from 0% to 32% (p = 0.009), and helmeted MCC admissions rose from 41% to 80% (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Paraganglioma of the prostatic urethra. A report of three cases and a review of the literature

OBJECTIVE: To determine the incidence and clinical presentation of prostatic urethral paragangliomas and to compare these findings with paragangliomas occurring in the other sites of the lower urinary tract. PATIENTS AND METHODS: The clinical records of three patients with prostatic urethral paragangliomas were reviewed, as was the histology of each specimen. The tumours were stained immunocytochemically with neuron-specific enolase, chromogranin, S100 protein, protein gene product 9.5, prostate-specific acid phosphatase and prostate-specific antigen. RESULTS: The three tumours occurred in elderly men, two of whom presented with haematuria, one of whom also had a vesical transitional cell carcinoma, and the third patient had obstructive symptoms due to co-existent prostatic hyperplasia. The histological appearances and immunocytochemical findings were consistent with paraganglioma. Treatment consisted of local excision and there were no recurrences or metastases at 5 and 6 years in two patients for whom follow-up was available. CONCLUSION: Urethral paragangliomas are rare tumours arising in elderly men and are hormonally inactive. Although haematuria may be the presenting symptom, it is important to exclude additional more common and possibly more sinister lesions such as transitional cell carcinoma. Local excision appears to be curative.     

A convenient method for guarding against localized mucositis during radiation therapy

Metal restorations, such as full gold crowns and dental implants, can cause forward and back scatter radiation during radiation therapy with a dose enhancement to adjacent tissues. Mucositis, one of the most common complications of the radiation treatment of oral, as well as other head and neck malignancies can result. A method for constructing a buccolingual guard in the clinical setting using hydroplastic material is described. The guard can be easily oriented and adapted to an existing radiation stent, adding positional stability and patient comfort. When adequate thickness of material is used, the guard can attenuate forward and back scatter radiation, separate the adjacent tissues from metal restorations, and protect the oral mucosa from localized incidents of mucositis.