Multiple sclerosis (MS) is a chronic neurological disease that
affects the brain and spinal cord. It is thought that MS is an
autoimmune disease, where a person’s immune system reacts to
its own body, namely the myelin sheath that surrounds the nerve
cells. Disease symptoms include vision problems, imbalance and
paralysis of the limbs. The exact cause of MS is still unknown, and
therapies without adverse effects are not available. Substantial
evidence suggests that the disease arises as a result of a certain
combination of environmental, genetic and infectious
circumstances. We hypothesize that herpesviruses create a
repertoire of autoreactive T-cells, which play a crucial role in the
demyelination process. To unravel the contribution of these
autoreactive T-cells to the pathogenesis of MS, the common
marmoset is used as an animal model for MS. The common
marmoset is a relevant model with a close genetic and
immunological proximity to humans, and it resembles the
disease in its clinical and pathological presentation. This thesis
describes how the common marmoset model for MS is refined
ethically, mechanistically, and conceptually to better understand
the underlying pathogenic processes, as well as to develop and
improve new targets for MS therapy.http://repub.eur.nl/res/pub/32462/120523_Jagessar%2C%20Sunil%20Anwar_Bewerkt.pdf
Hepatic Lipase (HL; EC 3.1.1.3) is an extracellular glycoprotein with phospholipase A1 and
triacylglycerol hydrolase activity. The human HL protein is encoded by the LIPC gene on
chromosome 15q21. Most of this protein is synthesized in the parenchymal cells of the liver
and secreted into the space of Disse where it binds to heparin sulfate proteoglycans.
Some synthesis of HL was also observed in macrophages. The HL protein is also present in
the steroidogenic adrenal glands, ovaries and, in small amounts, in the testes. By using
heparin, HL protein is displaced from its binding site. Human HL protein is a homodimer, the
monomer has a molecular weight of 65 kDa. In the metabolism of plasma lipoproteins HL
plays an important role; it mediates the conversion of high density lipoprotein subfraction 2
(HDL2) to high density lipoprotein subfraction 3 (HDL3), the conversion of intermediate density
lipoprotein (IDL) to low density lipoproteins (LDL), and the formation of small dense LDL
(sdLDL) from large buoyant LDL. HL has a role in postprandial lipid transport where it
facilitates the clearance of remnant lipoproteins by the liver. In adrenals and ovaries the HL
enzyme facilitates the delivery of HDL cholesterol for steroidogenesis, at least in the rat.
HL expression is determined by genetic, hormonal and nutritional factors, and by
body composition. HL activity is associated with a risk for Coronary Artery Diseases
(CAD). Whether high HL expression is anti- or pro-atherogenic depends on other genetic or
metabolic factors, e.g. concomitant hypertriglyceridemia [1,19]. Humans with visceral obesity
and insulin resistance or type 2 diabetes show increased levels of HL expression.
How HL gene expression is altered in insulin-resistant conditions is unknown. Relative to the
common LIPC C-allele (referring to the C/T polymorphism at the -514 position), carriers of the
T-allele have reduced post-heparin HL activity, and the T-allele is associated with dyslipidemia
and insulin resistance in healthy controls and in Familial Combined Hyperlipidemia (FCH).
In cell culture experiments using human HepG2 hepatoma cells, HL expression was found to
be increased by elevated levels of fatty acids and glucose, conditions that prevail
in insulin resistance. How these metabolic factors affect HL expression is largely unknown.
At first glance, deciding whether to get the PSA screening
test for prostate cancer seems to be pretty straightforward and attractive. It’s a simple
blood test that can pick up the prostate cancer long before your symptoms appear. After
all, your prostate cancer is earlier treated resulting in cure and better outcome. Therefore
prostate cancer screening seems to be suitable for public commercials. However, many
of the cancers that will be detected by screening are so slow-growing that might never
cause problems during mens life. Moreover, their diagnosis by biopsy, and treatment,
might be worse than the disease itself. Therefore, prostate cancer screening looks favourable;
however, watch out for the prostate cancer bomb.
