Brain biopsy in the diagnosis of cerebral mycosis fungoides

A case of cerebral mycosis fungoides co-existing with progressive multifocal leucoencephalopathy presented with dementia. Brain biopsy established the diagnosis of mycosis fungoides after cerebrospinal fluid examinations and computerised tomographic scanning of the brain produced non-specific abnormalities.     

Neonatal maternal separation opposes the facilitatory effect of castration on the respiratory response to hypercapnia of the adult male rat: Evidence for the involvement of the medial amygdala

Respiratory manifestations of panic disorder (PD) include a greater respiratory instability and enhanced responsiveness to CO₂ compared to normal individuals. Although the prevalence of PD is approximately three times greater in women compared to men, the origins of this sexual dimorphism remain poorly understood. Similar to PD patients, adult female rats previously subjected to neonatal maternal separation (NMS) show an increase in their ventilatory response to CO₂. Because this effect of NMS is not observed in males, we hypothesised that testosterone prevents NMS‐induced hyper‐responsiveness to CO₂. Pups subjected to NMS were placed in an incubator for 3 h d^‐1 from postnatal days 3‐12. Control pups remained undisturbed. At adulthood (8‐10 weeks of age), rats were then subjected either to sham surgery or castration. Fourteen days later, breathing was measured at rest (room air) and during acute exposure to hypercapnia (5 and 10% CO₂ for 10 minutes each) using plethysmography. To gain insight into the mechanisms involved, c‐fos expression was used as an indicator of neuronal activation. Brains were collected following air or CO₂ exposure for quantification of c‐fos positive cells by immunohistochemistry in selected regions, including the paraventricular nucleus of the hypothalamus, the dorsomedial hypothalamus and the amygdalar complex. Castration produced a 100% increase of hyperventilatory response to 10% CO₂ in control rats. Unexpectedly, castration had no effect on the hyperventilatory response of NMS rats. The intensity of the hypercapnic response was inversely correlated with c‐fos expression in the medial amygdala. We conclude that testosterone prevents the hyper‐responsiveness to CO₂, whereas NMS attenuates sensitivity to hormone withdrawal. We propose that an inhibitory influence from the medial amygdala contributes to this effect.     

Radiation-induced red cell damage: role of reactive oxygen species

BACKGROUND: Cellular blood components are irradiated to prevent graft- versus-host disease in transfusion recipients at risk for this syndrome. Because gamma radiation can result in the production of reactive oxygen species, the role of reactive oxygen species was investigated in radiation-induced red cell damage. STUDY DESIGN AND METHODS: Whole blood from normal donors was exposed to various doses of t-butyl hydroperoxide (0-1 mM) and/or to gamma-radiation (0-50 Gy). Oxidative damage was assessed by the extent of lipid peroxidation (measured by thiobarbituric acid-reactive substances [TBARS]) and hemoglobin oxidation. Fresh blood was divided into three parts-one initially irradiated and stored, another stored with portions irradiated weekly, and a third stored without irradiation. TBARS and hemoglobin oxidation were measured weekly. RESULTS: As expected, t- butyl hydroperoxide induced TBARS formation and hemoglobin oxidation in a dose-dependent fashion. The gamma-radiation not only increased hemoglobin oxidation and TBARS formation, but also enhanced the t-butyl hydroperoxide effect on red cells. Red cell storage increased TBARS generation and hemoglobin oxidation in a time-dependent fashion. When radiation was administered either initially or after weekly storage, TBARS production and hemoglobin oxidation were increased over that measured in unirradiated paired controls. CONCLUSION: Gamma radiation at clinically used doses increases lipid peroxidation and hemoglobin oxidation in human red cells. The effect of gamma-radiation is accentuated by blood storage and induces damage independent of time of storage.     

Multiple quantitative trait loci for blood pressure interacting epistatically and additively on Dahl rat chromosome 2

Our previous work demonstrated 2 quantitative trait loci (QTLs), C2QTL1 and C2QTL2, for blood pressure (BP) located on chromosome (Chr) 2 of Dahl salt-sensitive (DSS) rats. However, for a lack of markers, the 2 congenic strains delineating C2QTL1 and C2QTL2 could not be separated. The position of the C2QTL1 was only inferred by comparing 2 congenic strains, one having and another lacking a BP effect. Furthermore, it was not known how adjacent QTLs would interact with one another on Chr 2. In the current investigation, first, a critical chromosome marker was developed to separate 2 C2QTLs. Second, a congenic substrain was created to cover a chromosome fragment thought to harbor C2QTL1. Finally, a series of congenic strains was produced to systematically and comprehensively cover the entire Chr 2 segment containing C2QTL2 and other regions previously untested. Consequently, a total of 3 QTLs were discovered, with C2QTL3 located between C2QTL1 and C2QTL2. C2QTL1, C2QTL2, and C2QTL3 reside in chromosome segments of 5.7 centiMorgan (cM), 3.5 cM, and 1.5 cM, respectively. C2QTL1 interacted epistatically with either C2QTL2 or C2QTL3, whereas C2QTL2 and C2QTL3 showed additive effects to each other. These results suggest that BP QTLs closely linked in a segment interact epistatically and additively to one another on Chr 2.     

Inflammation occurs early during the Abeta deposition process in TgCRND8 mice

Alzheimer's disease (AD) is characterized by a progressive cognitive decline leading to dementia and involves the deposition of amyloid-beta (Abeta) peptides into senile plaques. Other neuropathological features that accompany progression of the disease include a decrease in synaptic density, neurofibrillary tangles, dystrophic neurites, inflammation, and neuronal cell loss. In this study, we report the early kinetics of brain amyloid deposition and its associated inflammation in an early onset transgenic mouse model of AD (TgCRND8) harboring the human amyloid precursor protein gene with the Indiana and Swedish mutations. Both diffuse and compact plaques were detected as early as 9-10 weeks of age. Abeta-immunoreactive (Abeta-IR) plaques (4G8-positive) appeared first in the neocortex and amygdala, then in the hippocampal formation, and lastly in the thalamus. Compact plaques (ThioS-positive) with an amyloid core were observed as early as diffuse plaques were detected, but in lower numbers. Amyloid deposition increased progressively with age. The formation of plaques was concurrent with the appearance of activated microglial cells and shortly followed by the clustering of activated astrocytes around plaques at 13-14 weeks of age. This TgCRND8 mouse model allows for a rapid, time-dependent study of the relationship between the fibrillogenic process and the inflammatory response during the brain amyloidogenic process.     

Overexpression of activated murine Notch1 and Notch3 in transgenic mice blocks mammary gland development and induces mammary tumors

The mouse mammary tumor virus (MMTV) provirus was found to target the Notch1 gene, producing insertional mutations in mammary tumors of MMTV/neu transgenic (Tg) mice. In these mammary tumors, the Notch1 gene is truncated upstream of the transmembrane domain, and the resulting Notch1 intracellular domain (Notch1(intra)), deleted of most extracellular sequences, is overexpressed. Although Notch1(intra) transforms mammary epithelial cells in vitro, its role in mammary gland tumor formation in vivo was not studied. Therefore, we generated MMTV/Notch1(intra) Tg mice that overexpress murine Notch1(intra) in the mammary glands. We observed that MMTV/Notch1(intra) Tg females were unable to feed their pups because of impaired ductal and lobulo-alveolar mammary gland development. This was associated with decreased proliferation of ductal and alveolar epithelial cells during rapid expansion at puberty and in early pregnancy, as well as decreased production of beta-casein. Notch1(intra) repressed expression of the beta-casein gene promoter, as assessed in vitro with a beta-casein/luciferase reporter construct. The MMTV/Notch1(intra) Tg females developed mammary gland tumors, confirming the oncogenic potential of Notch1(intra) in vivo. Furthermore, MMTV/Notch3(intra) Tg mice exhibited a very similar phenotype. Thus, these Tg mice represent novel models for studying the role of Notch1 or Notch3 in the development and transformation of the mammary gland.     

Time estimation in chronic insomnia sufferers

STUDY OBJECTIVE: The objective of the present study is 2-fold: (1) compare the time-estimation performance of chronic insomnia sufferers to that of good sleepers and (2) evaluate the severity of the sleep complaint in order to assess its association with the time-estimation performance. DESIGN: Between subjects design. PARTICIPANTS: The sample included 11 individuals suffering from chronic primary insomnia (7 women and 4 men, mean age = 44.64 years, SD = 12.71) and 11 good sleepers (5 women and 6 men, mean age = 48.00 years, SD = 7.86). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All participants completed a time-estimation task, namely a finger-tapping task. The results indicate no significant between-group differences on time-estimation data, as well as no significant relationship between severity of insomnia complaint and estimation of time. CONCLUSION: These results suggest that the tendency to misestimate sleep difficulties is not linked to impaired time estimation-specific processes in insomnia sufferers, as measured with the present task.     

Secular changes in incidence and mortality associated with Staphylococcus aureus bacteraemia in Quebec, Canada, 1991-2005.

In order to examine secular changes in the incidence and mortality associated with Staphylococcus aureus bacteraemia before and after the emergence of methicillin-resistant S. aureus (MRSA), a retrospective cohort study of 815 patients with S. aureus bacteraemia was performed in the Estrie region of Quebec, Canada, between 1991 and 2005. The primary outcome was all-cause 30-day mortality. Between 1991-1993 and 2003-2005, the proportion of cases attributed to endocarditis and pneumonia increased from 4% to 11% and from 2% to 11%, respectively, while that attributed to catheter infections decreased from 49% to 17%. MRSA was almost absent in 1991-1999, but accounted for 10% and 20% of cases in 2000-2002 and 2003-2005, respectively. The population incidence of bacteraemia caused by methicillin-susceptible S. aureus (MSSA) remained stable between 1997 and 2005, while that of MRSA increased from 0 to 7.4/100 000. Risk-factors for mortality included age, co-morbidities, female gender, residence outside the city of Sherbrooke, pneumonia (OR 3.35, 95% CI 1.96-5.73) or endocarditis (OR 2.89, 95% CI 1.67-5.01) as the source, and an absence of treatment. After adjusting for confounders, patients with MRSA bacteraemia had a higher mortality rate than those with MSSA bacteraemia (OR 2.21, 95% CI 0.99-4.96, p 0.053). Mortality in patients with MSSA bacteraemia was 19% (16/83) in 1991-1993, 23% (26/113) in 1994-1996, 29% (50/173) in 1997-1999, and 28% (52/185) in 2000-2002, decreasing to 15% (28/192) in 2003-2005, which impacted on the relative mortality rates of MRSA and MSSA. MRSA did not replace, but added to, an existing stable incidence of MSSA bacteraemia.