Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

Mechanism of long-term degeneration of arterialized vein grafts

This study examined long-term changes in the morphology and cellular kinetics of rabbit vein grafts transplanted into the carotid artery. Six grafts were studied 1 year after implantation. Although the circumference and thickness of the wall were not different than at 12 weeks, degenerative changes occurred. The endothelial lining of the graft appeared intact, but large segments of the graft surface no longer excluded Evans blue dye, suggesting increased permeability. Collections of red blood cells were noted within the intima. Several grafts had extensive subendothelial fibrin deposits, often associated with foam cells, and evidence of previous hemorrhage, but these changes did not stimulate significant smooth muscle cell proliferation. Increased permeability with entrance of proteins and erythrocytes into the intima may result from increased wall tension or from low shear rates at the wall. Similar changes may lead to atherosclerosis in human vein grafts at late times.     

A sexually dimorphic ratio of orbitofrontal to amygdala volume is altered in schizophrenia.

BACKGROUND: Neuroanatomic sexual dimorphisms have been correlated with behavioral differences between healthy men and women. We have reported higher orbitofrontal cortex to amygdala ratio (OAR) in women than men. Although gender differences in schizophrenia are evident clinically and correlate with neuroanatomic measures, their relationship to OAR has not been examined. METHODS: Magnetic resonance imaging was performed in 31 neuroleptic-na?ve schizophrenic patients (16 men) and 80 healthy volunteers (34 men), aged less than 50 years. An automated tissue segmentation procedure was combined with expert-guided parcellation of orbitofrontal and amygdala volumes. RESULTS: Men with schizophrenia had increased OAR relative to healthy men, whereas women had decreased OAR. Increased OAR in men with schizophrenia reflected abnormally low amygdala volumes, whereas decreased OAR in women reflected abnormally low orbitofrontal volumes. Less severe negative symptoms were associated with increased OAR in men but with decreased OAR in women. In men, increased amygdala volume was associated with greater symptom severity, whereas in women higher volumes of both amygdala and orbitofrontal regions were associated with lesser severity of negative symptoms. CONCLUSIONS: These opposite OAR abnormalities, whereby men show feminization and women masculinization, suggest gender-mediated effects of the underlying neuropathologic processes. The correlations with symptom severity suggest that neuroanatomic abnormalities in OAR reflect compensatory brain changes.     

Reciprocal relationships between general (Propofol) anesthesia and circadian time in rats.

Several common postdischarge symptoms, such as sleep disorders, headache, drowsiness or general malaise, evoke disturbances of circadian rhythms due to jet lag (ie crossing time zones) or shift work rotation. Considering that general anesthesia is associated with numerous effects on the central nervous system, we hypothesized that it may also act on the circadian timing system. We first determined the effects of the circadian timing on general anesthesia. We observed that identical doses of propofol showed marked circadian fluctuations in duration of effects, with a peak at the middle of the resting period (ie 7 h after lights on). Then, we examined the effects of general anesthesia on circadian timing, by analysing stable free-running circadian rhythms (ie in constant environmental conditions), an experimental approach used widely in circadian biology. Free-running rats were housed in constant darkness and temperature to assess possible phase-shifting effects of propofol anesthesia according to the time of the day. When administered around (+/-2 h) the daily rest/activity transition point, a 30-min propofol anesthesia induced a 1-h phase advance in the free-running rest-activity rhythm, while anesthesia had no significant resetting effect at other times of the day. Anesthesia-induced hypothermia was not correlated with the phase-shifting effects of propofol anesthesia. From our results, anesthesia itself can reset circadian timing, and acts as a synchronizing cue for the circadian clock.     

Histologic criteria for the diagnosis of erythrodermic mycosis fungoides and Sézary syndrome: a critical reappraisal

It is often difficult to make a clinical or histologic diagnosis of erythrodermic mycosis fungoides (MF) and Sézary syndrome (SS). Whereas the histologic parameters for making a diagnosis of MF with well-developed patch and plaque stage lesions are clearly defined, the same criteria appear to be less relevant for diagnosing MF in patients with erythroderma secondary to the disease. In order to better define the histologic features of erythrodermic MF and SS, we studied 28 routine histologic sections of 17 patients with known erythrodermic MF or SS. Sections were reviewed independently by 2 dermatopathologists. Each of 24 parameters was scored semi-quantitatively and the data were compared to data previously reported from a group of 64 patients with limited patch and plaque stage lesions of MF. When compared to biopsies from patients with limited patch/plaque lesions, biopsies taken from erythrodermic patients displayed more parakeratosis (p=0.0492) and acanthosis (p=0.0046), less disproportionate epidermotropism, fewer lymphocytes aligned within the basal layer (p=0.0045), fewer hyper-convoluted cells in the epidermis, more dermal hyperconvoluted cells (p=0.0191), more papillary dermal fibrosis (p=0.0002), more prominent teleangiectasias (p=0.0028) and more mitotic figures.
The histologic features of erythrodermic MF and Sézary syndrome are even more subtle than the features of patch and plaque stage MF, thus rendering the histologic diagnosis more difficult.     

Vesicoureteral reflux diagnosed in adulthood. Incidence of urinary tract infections, hypertension, proteinuria, back pain and renal calculi

Study purpose: To determine the incidence of urinary tract infections, hypertension, back pain, and renal calculi in adult patients with vesicoureteral reflux and reflux nephropathy. Methods: A group of 115 patients (16-60 years of age, median 28 years) with vesicoureteral reflux, combined with reflux nephropathy in 101 patients, first detected between 1967 and 1984, was studied retrospectively. The group comprised 99 women and 16 men. Results: Symptoms and findings associated with the urinary tract preceded the diagnosis of vesicoureteral reflux by median 14 years (1-60 years). Intravenous pyelography preceded investigation with micturating cystography in 99 patients. Fifteen patients had no urinary tract infections, 17 patients had only lower urinary tract infections, and 83 patients had upper with or without lower urinary tract infections. Females had 12 times more lower and seven times more upper urinary tract infections than males, whereas males had impairment of renal function and proteinuria more often than females. Hypertension was present in 39 patients (34%) and five times more frequent in patients with bilateral than in those with unilateral reflux nephropathy. The median age at the first recording of hypertension was 33 years (16-60 years). Malignant hypertension was uncommon and occurred in two patients. An older group (>45 years of age at presentation) of 19 patients showed a 90% incidence of hypertension compared with 23% in 96 patients in the younger group (⩽45 years of age at presentation). Back pain of varying type and severity was present in 48 patients (42%). A total of 38 renal calculi was found in 21 (18%) patients, of whom 14 were completely asymptomatic. Conclusions: The natural history of vesicoureteral reflux first detected in adulthood has shown a strikingly high incidence of urinary tract infections, arterial hypertension, back pain, and renal calculi.     

Role of arteriography in the preoperative evaluation of carotid artery disease

This retrospective study was undertaken to determine the role of arteriography in the treatment of patients being considered for carotid endarterectomy. The results of preoperative classification of disease severity by duplex ultrasound and arteriography were compared, and the impact of arteriography on patient management was ascertained. We reviewed the records of 83 patients who had carotid surgery planned on the basis of their clinical history and duplex scan results and who then underwent arteriography. Duplex scan results agreed with the classification of stenosis by arteriography in 87% of evaluated sides and were within one category in 98%. In 87% of the cases reviewed, the clinical presentation and duplex scan findings were sufficient for appropriate patient management. In the instances that arteriography was useful (13%), the need for arteriography was evident when the duplex scan (1) was technically inadequate or equivocal; (2) showed an unusual distribution of disease, atypical anatomy, or a recurrent lesion; or (3) demonstrated an internal carotid artery with diameter-reducing stenosis of less than 50% in a patient with hemispheric neurologic symptoms despite antiplatelet therapy.