Serial transplantation of NMU-induced rat mammary tumors: a model of human breast cancer progression

Human breast cancer is a heterogeneous disease that appears to progress from an in situ tumor to invasive cancer. Little is known about the molecular events driving this progression. Although microarray technology has helped us understand the genetic heterogeneity of breast cancer, its application to studying the transition from in situ to invasive disease is limited by the inability to follow the progression of a single patient's tumor. We previously used rat specific microarrays to show that N-methyl-N-nitrosourea induced tumors are similar to low-grade estrogen-receptor positive human breast cancer. Here, we transplanted these tumors through 5 generations of syngeneic hosts, and studied 65 resulting tumors. Most transplanted tumors gradually progressed from a noninvasive, low-grade cancer to a higher-grade invasive disease, losing p63 localization and basement membrane integrity. Invasive cancers frequently demonstrated a more mesenchymal phenotype with increased vimentin expression. Additionally, a unique transplant series is described with a phenotype similar to human basal-like breast cancer. Rat-specific Affymetrix gene arrays containing 15,866 gene probes identified genes that differentiated highly invasive tumors from those of low invasive potential. A linear regression analysis was used to find genes whose change in expression paralleled increasing invasive features independent of the transplant lineage of origin. Genes identified were assigned membership in cell adhesion, signal transduction, cell cycle and extracellular matrix groups, among others. This animal model overcomes the difficulty in studying human breast cancer progression. Our data support a gradual and continuous alteration in programs of gene expression during breast cancer invasion.     

Neurodegeneration and peroxidases

Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative diseases that affect different parts of the central nervous system. However, a review of the literature indicates that certain biochemical reactions involved in neurodegeneration in these three diseases are quite similar and could be partly identical. This article critically examines the similarities and, based on data from our own and other laboratories, proposes a novel explanation for neurodegeneration in these three diseases. We identified about 20 commonalities that exist in the neurodegenerative process of each disease. We hypothesize that there are two enzyme-catalyzed pathways that operate in affected neurons: an oxidative pathway leading to destruction of various neuronal proteins and lipids, and an apoptotic pathway which the body normally uses to remove unwanted and dysfunctional cells. Data from many laboratories indicate that oxidative reactions are primarily responsible for neurodegeneration, whereas apoptosis may well be a secondary response to the presence of neurons that have already been severely damaged by oxidative reactions. Attempts to inhibit apoptosis for the purpose of attenuating progression of these diseases may therefore be only of marginal benefit. Specific oxidative reactions within affected neurons led us to propose that one or more heme peroxidases may be the catalyst(s) involved in oxidation of proteins and lipids. Support for this proposal is provided by the recent finding that amyloi-beta peptide may act as a peroxidase in AD. Possible participation of the peroxidase activity of cytochrome c, herein designated as cytochrome c(px) to distinguish it from yeast cytochrome c peroxidase, is discussed. Of special interest is our recent finding that many compounds that cause attenuation of neurodegeneration are inhibitors of the peroxidase activity of cytochrome c. Several inhibitors were subsequently identified as suicide substrates. Such inhibitors could be ideally suited for targeted clinical approaches aimed at arresting progression of neurodegeneration. Finally, it is possible that immobilized yet still active peroxidase(s) may be present in protein aggregates in AD, PD, and ALS. This activity could be the catalyst for the slow, self-perpetuating and irreversible degeneration of affected neurons that occurs over long periods of time in these neurodegenerative diseases.     

Reinforcement sensitivity, coping, and delinquent behaviour in adolescents

Since 1964, the relationship between personality and criminal behaviour has been extensively studied. However, studies, which have examined the Eysenckian dimensions of extraversion, neuroticism and psychoticism have produced mixed results. Gray's [Gray, J. A. (1970). The psychophysiological basis of introversion-extroversion. Behavior Research and Therapy, 8, 249-266] Reinforcement Sensitivity Theory provides an alternative conceptualisation of the role of personality in criminal behaviour, and has generally produced more consistent findings. This study aimed to examine the relationship between reinforcement sensitivity and delinquent behaviour in a sample of 259 adolescents, and to examine the role that coping strategies play in this relationship. Hierarchical regression analyses revealed that use of problem solving mediated the relationship between reward sensitivity and delinquent behaviour, while use of non-productive coping strategies moderated the relationship between BAS drive and delinquency. Consequently, it was suggested that coping skills training could be an effective early intervention for delinquent behaviour.     

Are patients with severe depression traumatized by admission to an aged psychiatry ward?

BACKGROUND: Research on young psychiatric patients suggests that a significant proportion experience trauma and, in some cases, post-traumatic stress disorder (PTSD) as a result of hospitalization. This paper focuses on the evidence of trauma and PTSD associated with admission to an aged psychiatry ward. METHODS: Fifty former patients from three Melbourne hospitals were interviewed in their own homes, using a semi-structured, open-ended questionnaire. RESULTS: Thirty-four percent of participants reported having felt frightened, unsafe, powerless, and undermined at some time during their hospital stay. In 24% of cases these experiences could be described as "traumatic." None met criteria for PTSD. CONCLUSION: Most of the distressing experiences reported had been re-evaluated in the light of recovery or the passage of time. Nevertheless, finding ways to reduce the occurrence of such potentially traumatic experiences is clearly desirable. The evidence from this study suggests that providing opportunities for patients with depression to spend time apart from disturbed and disruptive patients would be helpful in this regard.     

Mycoplasma pneumoniae encephalopathy: recovery after intravenous immunoglobulin

In a case of Mycoplasma pneumoniae encephalopathy in a 7-year-old girl, the microorganism was identified by serologic and pharyngeal-swab polymerase chain reaction methods. Failure to detect or isolate the pathogen in the cerebrospinal fluid and the significant rapid clinical recovery of the patient after intravenous immunoglobulin administration suggest an immune-mediated mechanism. In critically ill patients with M. pneumoniae encephalopathy, prompt intravenous immunoglobulin treatment may be beneficial and can be considered as a primary or alternative therapeutic approach, especially when use of corticosteroids is insecure.     

The blood–brain barrier is intact after levodopa-induced dyskinesias in parkinsonian primates—Evidence from in vivo neuroimaging studies

It has been suggested, based on rodent studies, that levodopa (l-dopa) induced dyskinesia is associated with a disrupted blood–brain barrier (BBB). We have investigated BBB integrity with in vivo neuroimaging techniques in six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned primates exhibiting l-dopa-induced dyskinesia. Magnetic resonance imaging (MRI) performed before and after injection of Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) revealed an intact BBB in the basal ganglia showing that l-dopa-induced dyskinesia is not associated with a disrupted BBB in this model.     

Factors associated with deep sternal wound infection and haemorrhage following cardiac surgery in Victoria

Serious non-fatal complications of cardiac surgery include deep sternal wound infection (DSWI) and haemorrhage. Understanding the factors associated with these complications (both pre-operatively and intra-operatively) may aid in the prevention and avoidance of such complications. The aim of the current report is to identify factors associated with DSWI and haemorrhage for all patients undergoing cardiac surgical procedures in Victorian public hospitals from July 2001 to June 2005. Multiple logistic regression analysis incorporating preoperative and intraoperative variables was used to identify risk factors for DSWI and haemorrhage. There were 153 cases of DSWI (1.3%) and 413 cases of haemorrhage (3.5%) in 11,848 patients. The risk factors differ between DSWI and haemorrhage, with pre-operative factors being more commonly associated with DSWI and intra-operative factors associated with haemorrhage. Strategies directed towards minimising modifiable pre-operative risk factors (diabetes, preoperative dialysis, respiratory disease, being overweight and angina CCS Class 3 or 4) may reduce the incidence of DSWI. Improvements in operative factors (perfusion time, ventricular assist device, intraaortic balloon pump and aortic dissection) and surgical technique, may impact on reducing the incidence of haemorrhage.