The circadian basis of winter depression.

The following test of the circadian phase-shift hypothesis for patients with winter depression (seasonal affective disorder, or SAD) uses low-dose melatonin administration in the morning or afternoon/evening to induce phase delays or phase advances, respectively, without causing sleepiness. Correlations between depression ratings and circadian phase revealed a therapeutic window for optimal alignment of circadian rhythms that also appears to be useful for phase-typing SAD patients for the purpose of administering treatment at the correct time. These analyses also provide estimates of the circadian component of SAD that may apply to the antidepressant mechanism of action of appropriately timed bright light exposure, the treatment of choice. SAD may be the first psychiatric disorder in which a physiological marker correlates with symptom severity before, and in the course of, treatment in the same patients. The findings support the phase-shift hypothesis for SAD, as well as suggest a way to assess the circadian component of other psychiatric, sleep, and chronobiologic disorders.

Protease activity in the plasma of American oysters, Crassostrea virginica, experimentally infected with the protozoan parasite Perkinsus marinus.

Perkinsus marinus is responsible for disease and mortality of the American oyster, Crassostrea virginica. To investigate the interactions between P. marinus and oyster hemocytes, protease activity was measured in plasma of oysters collected 4 hr, 24 hr, 4 days, and 2 mo after experimental infection with P. marinus. A significant increase in protease activity was observed in oyster plasma 4 hr after injection with P. marinus, followed by a sharp decrease within 24 hr. Gelatin-impregnated gel electrophoresis showed the presence of 2 major bands (60 and 112 kDa) and 3 less prevalent bands (35, 92, and 200 kDa) with metalloproteinaselike activity in the plasma of noninfected oysters. Additional bands in the 40- to 60-kDa range, corresponding to P. marinus serine proteases, were observed in oyster plasma at early time points after infection. A transient, but significant, decrease in the activity of oyster metalloproteinases was observed at early time points after infection. Coincubation of oyster plasma with P. marinus extracellular products resulted in a decrease in oyster metalloproteinases and several P. marinus proteases. This study provides insights into the role of proteases in the pathogenesis of Dermo disease.

The Oregon Center for Complementary and Alternative Medicine career development program: innovation in research training for complementary and alternative medicine.

BACKGROUND: The burgeoning use of complementary and alternative medicine (CAM) highlights the need for high-quality research to discriminate between those approaches based on positive anecdotes or polished marketing and those that are consistently effective and safe. DESCRIPTION: To help meet this need, the Oregon Center for Complementary and Alternative Medicine has developed an innovative program to train researchers. The training program includes an individual mentoring and training plan, group mentoring, a clinical research class, proposal development, completion of an actual study, and journal club participation. EVALUATION: After 2 years the fellows have submitted 18 grants, presented 4 posters, submitted 7 articles, developed 2 treatment protocols, and earned 1 master of public health degree and 1 graduate certificate. CONCLUSIONS: This program helps experienced CAM practitioners quickly adopt a research perspective. We encourage other career development programs to extend training in research methods to individuals possessing a profound understanding of CAM.

Gender differences in posttraumatic stress disorder after motor vehicle accidents.

OBJECTIVE: Women have higher rates of posttraumatic stress disorder (PTSD) than men. The authors examined prior trauma, PTSD, major depression, anxiety disorder not including PTSD, and peritraumatic dissociation; current peritraumatic dissociation; and passenger injury as possible explanations for the different rates of acute PTSD in women and men after a serious motor vehicle accident. METHOD: Subjects age 18-65 years who had been in a serious motor vehicle accident (N=122) were assessed with the Structured Clinical Interview for DSM-III-R and the Peritraumatic Dissociative Experiences Questionnaire-Rater Version 1 month after the accident. RESULTS: Women did not differ from men in meeting the overall reexperiencing criterion for a diagnosis of PTSD (criterion B), but women were at greater risk for the specific reexperiencing symptoms of intense feelings of distress in situations similar to the motor vehicle accident and physical reactivity to memories of the motor vehicle accident. Women were 4.7 times more likely than men to meet the overall avoidance/numbing criterion (criterion C) and 3.8 times more likely to meet the overall arousal criterion (criterion D). Women were more likely than men to report the criterion C symptoms of avoiding thoughts and situations associated with the accident, loss of interest in significant activities, and a sense of foreshortened future and the criterion D symptoms of trouble sleeping, difficulty concentrating, and exaggerated startle response. Multiple logistic regression analysis indicated that the gender differences in acute PTSD were not associated with prior trauma, PTSD, peritraumatic dissociation, major depression, or anxiety disorder not including PTSD or with passenger injury. However, peritraumatic dissociative symptoms at the time of the accident were associated with a significantly higher risk for acute PTSD in women than in men. CONCLUSIONS: Gender differences in peritraumatic dissociation may help explain differences in risk for PTSD and for some PTSD symptoms in women and men.

A novel silencer element in the bovine papillomavirus type 4 promoter represses the transcriptional response to papillomavirus E2 protein.

The long control regions (LCRs) of mucosal epitheliotropic papillomaviruses have similar organizations: a promoter region, an enhancer region, and a highly conserved distribution of E2 DNA binding sites (C. Desaintes and C. Demeret, Semin. Cancer Biol. 7:339--347, 1996). The enhancer of these viruses is epithelial cell specific, as it fails to activate transcription from heterologous promoters in nonepithelial cell types (B. Gloss, H. U. Bernard, K. Seedorf, and G. Klock, EMBO J. 6:3735--3743, 1987). Using the bovine papillomavirus type 4 (BPV-4) LCR and a bovine primary cell system, we have shown previously that a level of epithelial specificity resides in a papillomavirus promoter region. The BPV-4 promoter shows an enhanced response to transcriptional activators in epithelial cells compared with that of fibroblasts (K. W. Vance, M. S. Campo, and I. M. Morgan, J. Biol. Chem. 274:27839--27844, 1999). A chimeric lcr/tk promoter suggests that the upstream BPV-4 promoter region determines the cell-type-selective response of this promoter in fibroblasts and keratinocytes. Promoter deletion analysis identified two novel repressor elements that are, at least in part, responsible for mediating the differential response of this promoter to upstream activators in fibroblasts and keratinocytes. One of these elements, promoter repressor element 2 (PRE-2), is conserved in position and sequence in the related mucosal epitheliotropic papillomaviruses, BPV-3 and BPV-6. PRE-2 functions in cis to repress the basal activity of the simian virus 40 promoter and binds a specific protein complex. We identify the exact nucleotides necessary for binding and correlate loss of binding with loss of transcriptional repression. We also incorporate these mutations into the BPV-4 promoter and demonstrate an enhanced response of the mutated promoter to E2 in fibroblasts. The DNA binding protein in the detected complex is shown to have a molecular mass of approximately 50 kDa. The PRE-2 binding protein represents a novel transcriptional repressor and regulator of papillomavirus transcription.

Debriefing following trauma.

In this paper we address three areas. First we review the literature on clinical intervention using debriefing, second we examine who attends debriefings by looking at a study of the 1989 plane crash at Ramstein, Germany and lastly we examine the effect of natural debriefing, i.e., talking to family and friends on psychiatric outcome in disaster workers by looking at a study of the Sioux City, Iowa United plane crash, 1989. Our data suggest that those with high exposure and females were more likely to attend a debriefing. People most likely to talk about the disaster with spouse/significant other, coworker and/or another person were: those with acute PTSD, higher total and intrusive Impact of Event symptoms, older, married, those with higher levels of education and higher levels of disaster exposure. Better understanding of who attends formal debriefings will help identify potential high-risk groups. Similarly, whether talking about the disaster is associated with fewer or greater psychological symptoms is important to understanding the outcome, mechanisms, and risks of debriefing.

Peritraumatic dissociation following motor vehicle accidents: relationship to prior trauma and prior major depression.

Individuals who dissociate at the time of a traumatic event (peritraumatic dissociation) are more likely to develop acute and chronic posttraumatic stress disorder (PTSD). However, little is known about who is at risk of peritraumatic dissociation. Motor vehicle accident subjects (N = 122) were systematically recruited and followed over 12 months. We used the Structured Clinical Interview for DSM-III-R (SCID) and the Peritraumatic Dissociative Experiences Questionnaire-Rater Version (PDEQ-RV). Younger subjects were more likely to experience peritraumatic dissociation as were white versus nonwhites, and single versus married subjects. Younger subjects reported a greater number of peritraumatic dissociative symptoms as did subjects with an injured passenger. After adjusting for age and passenger injury, prior major depression was significantly related to more peritraumatic dissociative symptoms. An interaction of age and prior major depression indicated that those who were younger and reported a history of major depression had the greatest number of peritraumatic dissociative symptoms.

Peritraumatic dissociation and posttraumatic stress disorder following motor vehicle accidents.

OBJECTIVE: This study examined the relation between peritraumatic dissociation and posttraumatic stress disorder (PTSD) in victims of motor vehicle accidents. METHOD: Victims of serious motor vehicle accidents (N = 122) were assessed for peritraumatic dissociation with the Peritraumatic Dissociative Experiences Questionnaire-Rater Version and followed longitudinally to assess acute and chronic PTSD (1 month and 3 months after the accident) with the Structured Clinical Interview for DSM-III-R. RESULTS: The most common peritraumatic dissociative symptom was time distortion (56.6%). Subjects with peritraumatic dissociation were 4.12 times more likely than those without to have acute PTSD and 4.86 times more likely to develop chronic PTSD. The risk was independent of risk associated with the presence of PTSD before the accident. CONCLUSIONS: Peritraumatic dissociation is common following motor vehicle accidents and is a risk factor for acute and chronic PTSD, independent of risk associated with prior PTSD.

An enhanced epithelial response of a papillomavirus promoter to transcriptional activators.

Mucosal epitheliotropic papillomaviruses have a similar long control region (LCR) organization: a promoter region, an enhancer region, and a highly conserved distribution of E2 DNA binding sites. The enhancer of these viruses is epithelial-specific, as it fails to activate transcription from heterologous promoters in nonepithelial cell types (Gloss, B., Bernard, H. U., Seedorf, K., and Klock, G. (1987) EMBO J. 6, 3735-3743; Morgan, I. M., Grindlay, G. J., and Campo, M. S. (1999) J. Gen. Virol. 80, 23-27). Studies on E2 transcriptional regulation of the human mucosal epitheliotropic papillomaviruses have been hindered by poor access to the natural target cell type and by the observation that some of the human papillomavirus promoters, including human papillomavirus-16, are repressed in immortalized epithelial cells. Here we present results using the bovine papillomavirus-4 (BPV-4) LCR and a bovine primary cell system as a model to study the mechanism of E2 transcriptional regulation of mucosal epitheliotropic papillomaviruses and the cell type specificity of this regulation. E2 up-regulates transcription from the BPV-4 LCR preferentially in epithelial cells (Morgan, I. M., Grindlay, G. J., and Campo, M. S. (1998) J. Gen. Virol. 79, 501-508). We demonstrate that the epithelial-specific enhancer element of the BPV-4 LCR is not required for the enhanced activity of E2 in epithelial cells and that the BPV-4 promoter is more responsive, not only to E2, but to other transcriptional activators in epithelial cells. This is the first time a level of epithelial specificity has been shown to reside in a papillomavirus promoter region.

Acute and chronic posttraumatic stress disorder in motor vehicle accident victims.

OBJECTIVE: This study reports the rates of acute and chronic posttraumatic stress disorder (PTSD) in a suburban community study group of 122 victims of serious motor vehicle accidents and a comparison group of 42 (who had been involved in minor, non-motor-vehicle accidents) followed over 12 months. METHOD: Motor vehicle accident victims were systematically recruited and examined with comparison subjects at 1, 3, 6, 9, and 12 months after the accident. The authors used the Structured Clinical Interview for DSM-III-R to assess DSM-III-R axis I disorders including PTSD. RESULTS: One month after the accident, 34.4% of the motor vehicle accident victims met criteria for PTSD (versus 2.4% of the comparison subjects). Similarly, at 3 and 6 months, rates of PTSD were higher (25.2% and 18.2%) in the motor vehicle accident victims than in the comparison group. Female victims were 4.64 times more likely than male victims to have PTSD at 1 month. Victims with a history of PTSD were 8.02 times more likely at 1 month and 6.81 times more likely at 3 months to have PTSD than those without a history of PTSD. Having an axis II disorder increased the risk for PTSD at 6 months. After adjustment for a history of PTSD and potentially confounding variables, women were 4.39 times more likely than men to develop PTSD at 1 month but did not have a higher risk for chronic PTSD; at 6 months, those with an axis II disorder were at greater risk of PTSD. CONCLUSIONS: Rates of PTSD are high in victims of serious motor vehicle accidents and remain high 9 months later. Female victims have an increased risk of acute but not chronic PTSD. Individuals with a history of PTSD are at risk of acute and chronic PTSD. An axis II disorder increases the risk for chronic but not acute PTSD.

Posttraumatic stress disorder and identification in disaster workers.

OBJECTIVE: Disaster workers who work with deceased victims are at increased risk of posttraumatic stress disorder (PTSD). Identification with the deceased has been proposed as one of the mechanisms in this stress-illness relationship. To examine this hypothesis, this study investigated three types of identification with the dead in a group of disaster workers: identification with the deceased as oneself, identification with the deceased as a friend, and identification with the deceased as a family member. METHOD: Fifty-four volunteer disaster workers who worked with the dead following an explosion on the USS Iowa naval ship were assessed 1, 4, and 13 months after the disaster. PTSD symptoms (measured with the DSMPTSD-IV scale), intrusive and avoidant disaster-related symptoms (measured with the Impact of Event Scale), somatization and general distress (measured with the SCL-90-R), and health care utilization were assessed. RESULTS: Disaster workers who reported identification with the deceased as a friend were more likely than those who did not to have PTSD, more intrusive and avoidant symptoms, and greater levels of other posttraumatic symptoms including somatization. Disaster workers who reported identification with the deceased as a family member had greater intrusive symptoms 1 month after the disaster than those who did not. There were no differences between those who did and did not identify with the deceased as self. Health care utilization was not associated with identification. CONCLUSIONS: Identification with the deceased is a risk factor for PTSD and posttraumatic symptoms in disaster workers exposed to the dead. Identification with the dead as a friend is specifically associated with higher risk for these workers.

Application of normal avian gut flora by prolonged aerosolization onto turkey hatching eggs naturally exposed to Salmonella.

A commercial preparation of normal avian gut flora (NAGF) was aerosolized for an extended period over turkey hatching eggs during pipping and hatching to examine any protective effects against natural exposure to salmonellae. Turkey hatching eggs, produced by salmonellae-infected breeder flocks and hatched in a commercial hatchery with a history of salmonellae contamination, were used in two trials. In Trial 1, four doses of NAGF inoculum per hatching egg were aerosolized through an automated hatcher fogging system during the final 48 hr of the pipping and hatching process. In Trial 2, two doses of NAGF inoculum were aerosolized in a like manner. In both trials, poults were exposed to Salmonella montevideo during hatching, as indicated by samples collected at the time of pull. At day 7, treated poults in both trials were culture negative for salmonellae and control poults were culture positive for salmonellae. In Trial 1, control poults were infected with Salmonella brandenburg, and in Trial 2, control poults were infected with S. montevideo. These studies justify further critical evaluation of the protective effects of prolonged aerosolization of normal avian gut flora during pipping and hatching against salmonellae colonization in turkey poults.

Isolation and identification of Ornithobacterium rhinotracheale from commercial broiler flocks on the Delmarva peninsula.

The growth and biological characteristics of isolates of Ornithobacterium rhinotracheale (ORT) from commercial broiler chickens in the mid-Atlantic region of the U.S.A. appear to be identical to those previously reported in the literature. The clinical disease and lesions are also similar to those reported from other poultry growing regions including South Africa and Europe. The diagnostic cases included in this report were often associated with known respiratory pathogens, namely, lentogenic Newcastle disease virus, and infectious bronchitis virus, and Escherichia coli bacteria. The role of ORT in the disease cases presented in this report is unclear.