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L Kappeler

Publications and source records attributed to L Kappeler.

8 recordsLinked to original sources
PubMed2006

Gender differences in spontaneous cervical artery dissection.

We analyzed sex differences in 696 patients with spontaneous cervical artery dissection. There were more men (n = 399; p < 0.0001), and men showed a higher frequency of hypertension (31% vs 15%; p < 0.0001). Women were younger (42.5 +/- 9.9 vs 47.5 +/- 9.3 years; p < 0.0001), had more often multiple dissections (18 vs 10%; p = 0.001), migraine (47 vs 20%; p < 0.0001), and tinnitus (16 vs 8%; p = 0.001). Outcome and mortality were similar in both sexes.

Adult↗
PubMed2006

Pituitary cocaine- and amphetamine-regulated transcript expression depends on the strain, sex and oestrous cycle in the rat.

Cocaine- and amphetamine-regulated transcript (CART) mRNA and peptides are abundant in the adenohypophysis, but their role in pituitary function has not yet been elucidated. CART peptides were recently shown to colocalise with luteinising hormone (LH) or prolactin in rat anterior pituitary, and contradictory results concerning the peptide effects on pituitary hormonal secretions were obtained in vitro from pituitary cell cultures. Thus, we reinvestigated the expression of CART mRNA within the pituitary. Immunohistochemistry for pituitary hormones was performed on sections from adult male Wistar rats followed by in situ hybridisation using CART mRNA antisense 35S-labelled probes. The most represented CART-expressing cells were lactotrophs (42 +/- 1% of CART cells) and gonadotrophs (32 +/- 3%), followed by thyrotrophs (10 +/- 2%), corticotrophs (7 +/- 2%) and somatotrophs (6 +/- 1%). In the pars tuberalis, CART mRNA was easily detectable in gonadotrophs and lactotrophs and, to a lesser extent, in corticotrophs and thyrotrophs. CART peptide was quickly and potently released from perifused pituitary by depolarisation (K+ 30 mM for 15 min; 465 +/- 37% over basal release, n = 5). Gonadotrophin-releasing hormone and thyrotrophin-releasing hormone (0.1 microM) were also active to a lesser extent (138 +/- 11% and 71 +/- 17, n = 7, respectively). CART (0.1 microM) did not modify basal LH or prolactin release but selectively inhibited K+-induced LH release without affecting K+-induced prolactin secretion. Pituitary CART mRNA and content were sex dependent and varied during the oestrous cycle, being lower in dioestrous 2. Pituitary CART content also varied widely amongst rat strains being five to six-fold higher in Wistar and Fischer rats compared to Brown Norway and Lou C rats. Ageing differentially affected pituitary CART mRNA and content, resulting in a marked decrease in Lou C and an increase in Wistar and Sprague-Dawley rats. Taken together, these results suggest that pituitary CART expression is dependent of the sex steroid environment and may be physiologically involved in LH secretion.

Aging↗
PubMed2006

Impact of comorbidity on ischemic stroke outcome.

OBJECTIVE: To evaluate the impact of comorbidity on stroke outcome of patients admitted to a general ward (GW) and a stroke unit (SU). METHODS: Data of 266 patients with acute ischemic stroke (GW: 103, SU: 163) were collected prospectively for 13 months. Clinical and radiological findings, and the Charlson Comorbidity Index (CCI) were recorded. Predictors of outcome 4 months after stroke were analyzed. Favorable outcome was defined as modified Rankin Scale (mRS) score of < or = 2, unfavorable as mRS >2. RESULTS: The mean age of the patients was 67.2 years (SD = 14.4), the mean CCI 1.2 (SD = 1.4). In univariate analysis, small artery disease predicted favorable outcome (P < 0.001) and age (P = 0.022), high National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001), high CCI (P < 0.001), treatment in a GW (P = 0.004), coronary artery disease (P = 0.02), dementia (P = 0.009), diabetes (P = 0.005) and atrial fibrillation (P < 0.001) unfavorable outcome after 4 months. In multivariate analysis, high NIHSS score (P < 0.001), atrial fibrillation (P = 0.004), coronary artery disease (P = 0.012) and diabetes (P = 0.031) were predictors of unfavorable outcome. CONCLUSIONS: Comorbidity has a significant impact on stroke outcome. In addition to stroke severity, atrial fibrillation, coronary artery disease and diabetes were predictors of outcome after stroke, but not the sum of the CCI.

Adult↗
PubMed2005

[Biological aspects of longevity and ageing].

Despite very different life expectancies, a 2-year-old mouse, a 12-year-old dog, a 32-year-old chimpanzee or an 80-year-old man will share many common deficits such as a reduction in tissue elasticity, immunological responses, muscular strength, sensory perceptions, reflexes, as well as memory losses and increase of age-associated diseases (osteoporosis, osteoarthritis, type II diabetes, cardiovascular diseases, cataract and macular degeneration, neurodegenerative diseases, to name only a few...). With the increase of life expectancy in human species, ageing has become a major concern for the society, both at the human and financial level. The main challenge for biologists studying ageing is to understand how the multiple effects quoted above, so easily identifiable in various species, are nonetheless so coordinate among individuals of a given species. The acquisition of this fundamental knowledge will be essential to reach the ultimate goal of healthy ageing for human populations. At the present time, three types of recent developments on ageing research can be distinguished: 1) A consensus on evolutionist theory of ageing is developing. This theory is based on the fact that long-lived species usually arise from protected ecological niches. It implies that phenotypes which are expressed late in "aged survivors" are beyond natural selection. So, alleles underlying this late expression being adaptive or not ("good" or "bad"), contribute only slightly to the pool of genes of the following generation. 2) Study of laboratory models like the nematode C. elegans or fly D. melanogaster have enabled the observation that single-gene invalidation can increase lifespan. Interestingly, some of these changes seem to imply a common process through insulin/IGF-1 (insulin like growth factor-I) orthologue, energy metabolism and growth implicated hormones, as well as protection against free radicals. 3) In the mouse, several genes mutation increase lifespan and are associated with a decrease in growth hormone (GH) secretion as well as its main effector IGF-1. The study of such transgenic mutants, in parallel with the well-known effect of the caloric restriction on ageing, open several tracks which should allow determining common mechanisms which regulate the mammalian lifespan.

Aged↗
PubMed2004

Plasma and hypothalamic peptide-hormone levels regulating somatotroph function and energy balance in fed and fasted states: a comparative study in four strains of rats.

Both growth hormone (GH)/insulin growth factor (IGF)-1 axis and energy balance have been implicated in longevity independently. The aim of the present study was to characterize the effect of a 72-h fasting period at 3 months of age in four different rat strains: (i) Wistar and (ii) Fischer 344 rats, which develop obesity with age, and (iii) Brown Norway and (iv) Lou C rats, which do not. Wistar rats ate more, were significantly bigger, and presented with higher plasma leptin and lower ghrelin levels and hypothalamic growth hormone-releasing hormone (GHRH) content than rats from the three other strains. Plasma insulin and IGF-1 levels were lower in Brown Norway and Lou C rats, and somatostatin content was lower in Brown Norway rats only. Glycaemia was lower in Lou C rats that displayed a lower relative food intake compared to Fischer and Wistar rats. Brown Norway rats showed a greater caloric efficiency than the three other strains. Concerning major hypothalamic neuropeptides implicated in feeding, similar amounts were detected in the four strains for neuropeptide Y, agouti-related peptide, galanin, melanin-concentrating hormone, alpha-melanocortin-stimulating hormone (alpha-MSH) and corticotropin-releasing hormone. Orexin A appeared to be slightly elevated in Fischer rats and cocaine amphetamine-regulated transcript (CART)(55-102) diminished in Brown Norway. At the mRNA level, orexin A, GHSR1, alpha-MSH and CART expression were higher in Wistar and Lou C rats. Principal component analysis confirmed the presence of two main factors in the ad libitum rat population; the first being associated with growth-related parameters and the second being associated with food intake regulation. Hypothalamic GHRH and somatostatin content were positively correlated with feeding-related neuropeptides such as alpha-MSH for GHRH, and orexin A and CART for both peptides. Plasma ghrelin levels were negatively correlated with leptin and IGF-1 levels. Finally, a 72-h fasting period affected minimally body weight, plasma IGF-1 and leptin levels in Lou C rats compared to the three other strains, and plasma insulin levels were less affected in Brown Norway rats. In conclusion, Wistar shorter life span is consistent with its already fatter phenotype at 3 months of age. In terms of IGF-1, glycaemia and leptin responses to fasting, the Lou strain, which presents with a low food intake/body weight and caloric efficiency, is the least affected. The link between food intake regulation, GH axis and ageing is further demonstrated by principal component analysis, where GHRH and somatostatin were found to be strongly associated with energy homeostasis parameters.

Aging↗
PubMed2003

Age-associated changes in hypothalamic and pituitary neuroendocrine gene expression in the rat.

A cDNA membrane array displaying 1183 probes was used to detect hypothalamic and pituitary changes in gene expression accompanying ageing and age-associated pituitary macroadenomas. Four groups of male Sprague-Dawley rats (3-, 15-, 24-month-old and 24-month-old with prolactinoma) were compared in two independent hybridizations. cDNA array data were confirmed and completed by comparative reverse transcriptase-polymerase chain reaction on selected genes. The expression of 454 and 116 mRNAs was detected in hypothalamus and pituitary, respectively. Growth hormone (GH) mRNA alone represented 85% of total gene expression in the gland of young rats, and other pituitary hormone transcripts 2.8%, while melanin-concentrating hormone (MCH) mRNA, the most expressed neuropeptide transcript involved in neuroendocrine regulation, accounted for only 0.8% of total hypothalamic transcripts. The proportion of genes modified in the hypothalamus and pituitary was rather modest: 1.5% and 5.2%, respectively, for ageing per se, and 1.1% and 5.2% for age-associated macroprolactinomas. Among pituitary specific RNAs, GH mRNA expression was notably decreased with age. At the hypothalamic level, expression of genes directly involved in GH regulation, such as somatostatin and growth hormone-releasing hormone, was not altered, while neuropeptide transcripts involved in feeding behaviour [orexin/hypocretin, MCH, pro-opiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART)] were significantly altered. In addition, a few ubiquitous transcripts (hnRNP-K, PFKm, CCND 2, calponin and set) were differently affected in both tissues. Modifications in hypothalamic orexigenic (orexin, MCH) and anorexigenic (POMC, CART) gene expression are in keeping with an age-associated decrease in energy consumption but a higher one in the presence of macroprolactinomas.

Aging↗
PubMed2000

Differential pituitary gene expression profiles associated- to aging and spontaneous tumors as revealed by rat cDNA expression array.

Aging of the rat pituitary is often accompanied by the occurrence of adenomas. We asked whether complementary DNA hybridization array was adapted to identify gene expression patterns linked to aging and associated spontaneous adenomas. Thus, [32P]dATP-labeled cDNAs were prepared from pituitaries of three month-old rats (Y) and tumor-bearing 20-28-month-old rats (OT). The cDNAs were hybridized to identical membrane arrays allowing to study simultaneously 588 known genes (Clontech 7738-1). Among the 79 genes detected, the GH gene was predominantly expressed in both groups. Twenty-eight genes in the OT group and 15 in the Y group were found to be expressed at a higher level. The largest differences were of about 17 fold and were observed for the galanin and glutathione S transferase genes in the Y and OT groups, respectively. Relative RT-PCR was applied to validate the OT versus Y expression pattern obtained via cDNA array hybridization. The results were consistent for 14 out the 15 genes tested. In the light of these results, differential membrane array hybridization appears suitable to identify gene expression profiles associated with pituitary aging.

Adenoma↗