Increased expression of prion protein is associated with changes in dopamine metabolism and MAO activity in PC12 cells

Prion diseases of humans and animals occur following infection with infectious agents containing PrP(Sc) or in situations in which there is a mutation of the prion protein (PrP) gene. The cellular prion protein (PrP(C)) is a sialoglycoprotein that is expressed predominantly in neurons. PrP(C) is converted into a pathogenic form of PrP (PrP(Sc)), which is distinguishable from PrP(C) by its relative resistance to protease digestion. A number of postulates have been advanced for the function of normal PrP (PrP(C)), but this issue has not been resolved. To investigate the function(s) of PrP(C), we established clonal PC12 cell lines, which have elevated PrP(C) expression. The results show that there were alterations in dopamine metabolism and in monoamine oxidase (MAO) activity in transfected PC12 cells that overexpress PrP(C). There was an increase in concentration of DOPAC, a metabolite of dopamine, and in MAO activity in cells overexpressing PrP(C). MAO is involved in oxidative degradation of dopamine (DA). Our data suggest that PrP(C) plays a role in DA metabolism by regulating MAO activity.     

Assaults by patients on psychiatric residents: a survey and training recommendations

OBJECTIVE: A survey was conducted to determine the frequency and severity of assaults on psychiatric residents and the level of training they receive in the management of violent patients. METHODS: In early 1997 a survey was randomly distributed to 2,553 psychiatric residents, who represented half of all psychiatric residents in the United States. The survey asked about experiences of assaults and training received in management of violent patients. RESULTS: Completed surveys were received from 517 residents, for a 20 percent response rate. Seventy-three percent reported being threatened, and 36 percent had been physically assaulted. A third received no training in managing violent patients, and a third described their training as inadequate. CONCLUSIONS: Two-thirds of psychiatric residents are either undertrained or feel undertrained in dealing with violent patients. The authors propose a training curriculum based on recommendations of an American Psychiatric Association task force report on clinician safety.     

Full-thickness skin graft from the ulnar aspect of the wrist to cover defects on the hand and digits

Skin defects on the volar surface of the hand and digits are commonly treated with skin grafts. Many donor sites capable of providing adequate skin have already been reported. Ideal conditions for the donor site depend on skin color, texture, durability, and size. The authors describe the use of a new donor site for harvesting skin grafts to repair relatively small skin defects on the hand and digits. They used full-thickness skin grafts from the ulnar aspect of the wrist to reconstruct burn contractures and syndactyly in 20 patients. Their grafts provided an ideal color and texture match, and normal function of the hand and digits was restored. The donor site was closed directly, and the resulting scar was inconspicuous.     

Histomorphometric analysis of age-related structural changes in human clitoral cavernosal tissue

PURPOSE: To characterize age-associated histological changes of human clitoral cavernosal tissue and to determine whether age-related histological changes of clitoral cavernosal tissue correlate with vascular disease-related mortality. MATERIALS AND METHODS: Human clitorises were obtained from 15 fresh cadavers (age: 11 to 90 years) and from 3 patients undergoing clitoral surgery (age: 6 months to 15 years). Cross sections of the clitorises were stained with Masson's trichrome and utilized for computer assisted histomorphometric image analysis to determine the clitoral cavernosal content of smooth muscle and connective tissue. RESULTS: These studies revealed a strong link between increase in age and decreased clitoral cavernosal smooth muscle fibers. In histomorphometry, the percentage of clitoral cavernosal smooth muscle (mean +/- standard error) in an age group of 6 months to 15 years (n = 4) was 65+/-1.5, in 44 to 54 years (n = 7) was 50+/-1.2, and in 55 to 90 years (n = 7) was 37+/-1.3 (ANOVA, p = 0.0001). In the 18 tissues studied, decrease in the percentage of clitoral cavernosal smooth muscle significantly correlated with increase in age (simple regression, r = 0.61). In the age group of 44 to 90 years, clitoral cavernosal fibrosis was significantly greater in the presence of cardiovascular disease-related mortality compared with those without cardiovascular disease-related mortality. CONCLUSION: This study shows that aging women undergo histological changes in clitoral cavernosal erectile tissue. Vascular risk factors may adversely affect the structure of clitoral cavernosal tissue. These findings may be of importance in the pathophysiology of age-associated female sexual arousal disorders.     

Apoptosis induced by inhibition of contact with extracellular matrix in mouse collecting duct cells

Cell-matrix interactions have major effects upon phenotypic features such as gene regulation, cytoskeletal structure, differentiation and aspects of cell growth control. Detachment from the matrix epithelial cells induces programmed cell death, and this cell detachment induced apoptosis has been referred to as 'anoikis'. This study was undertaken to determine whether apoptosis is induced by inhibition of contact with extracellular matrix (ECM) in collecting duct cells and to investigate the signaling mechanisms of the process. Upon detachment from ECM, mouse inner medullary collecting duct cells (mIMCD-3) and mouse outer cortical collecting duct cells (M-1), which were derived from an SV40 transgenic mouse, entered into programmed cell death. Forced suspension of mIMCD-3 or M-1 cells did not affect the expression of Bcl-2-related proteins and did not activate c-Jun NH(2)-terminal kinase. Detachment of cells from ECM activated p38 mitogen-activated protein kinase (p38), but its inhibition with SB203580 did not protect cells from anoikis. Detachment of cells from matrix inhibited NF-kappaB activity, and the inhibition of NF-kappaB activity by overexpression of nonphosphorylatable I-kappaB increased detachment-induced apoptotic cell death in M-1 cells. Forced suspension of M-1 cells still activated p53 activity. Caspase-8 was activated during anoikis, but the time course of its activation was in accordance with DNA fragmentation. These results indicate that detachment from ECM induces apoptosis in the kidney collecting duct cells. Changes in expression levels of Bcl-2-related proteins or activation of JNK/p38 kinase are not critical for anoikis. Decrease in NF-kappaB activity and activation of p53 induced by inhibition of interaction with ECM play roles in anoikis in SV-40-transformed collecting duct cells. Caspase-8 is activated during detachment-induced apoptosis, the mechanisms of which are independent of activation of cell death receptors. Copyright Copyright 1999 S. Karger AG, Basel     

Clinical application of the M-numbers of aortic cannulas during hypothermic cardiopulmonary bypass in pediatric patients

A standardized system to describe the pressure-flow characteristics of a given cannula has recently been proposed and has been termed the M-number system. Using 3 different sizes of aortic cannulas in 50 pediatric cardiac patients on hypothermic cardiopulmonary bypass, we analyzed the correlation between experimentally and clinically derived M-numbers and found it to be positive. Clinical M-numbers were typically 0.35 to 0.55 greater than experimental M-numbers and correlated inversely with a patient's temperature change; this was most probably due to increased blood viscosity arising from hypothermia. This inverse relationship was more marked in higher M-number cannulas. The clinical data obtained in this study suggest that the experimentally derived M-number correlates strongly with the clinical performance of the cannula and that the influence of temperature is significant.