Elevated PTEN levels account for the increased sensitivity of ethanol-exposed cells to tumor necrosis factor-induced cytotoxicity.

Tumor necrosis factor alpha (TNF) is known to be one of the primary causative cytokines inflicting the characteristic damage to hepatocytes seen in alcoholic liver disease. TNF activates both cell survival and death-inducing signaling pathways. The balance between these two prongs determines the fate of the cell and the onset of disease.

[Less refusal to participate in HIV screening among pregnant women in the Amsterdam region since the introduction of standard HIV screening using the opting-out method].

In 2003 the Municipal Health Service in Amsterdam started to screen pregnant women for HIV according to the opting-out method. In this method the HIV test is routinely included in the prenatal screening along with hepatitis B virus (HBV) and syphilis. If the woman does not want to be tested for HIV then she must actively opt out of this test.

Inhibition of insulin-like growth factor I receptor tyrosine kinase by ethanol.

Ethanol inhibits insulin and insulin-like growth factor-I (IGF-I) signaling in a variety of cell types leading to reduced mitogenesis and impaired survival. This effect is associated with inhibition of insulin receptor (IR) and insulin-like growth factor-I receptor (IGF-IR) autophosphorylation, which implicates these receptors as direct targets for ethanol. It was demonstrated previously that ethanol inhibits the autophosphorylation and kinase activity of the purified cytoplasmic tyrosine kinase domain of the IR.

Cellular signaling mechanisms in alcohol-induced liver damage.

Chronic excessive alcohol intake is associated with multiple liver defects ranging from mild steatosis to advanced cirrhosis. However, the mechanisms by which chronic ethanol intake affects liver function remain a matter of intense debate and investigation. The liver is the major site of ethanol metabolism in the body, and a wide range of metabolic alterations is associated with ethanol intake.

Pharmaco-economic evaluation of targeted hepatitis A vaccination for children of ethnic minorities in Amsterdam (The Netherlands).

Objective: Estimate cost-effectiveness of vaccination against hepatitis A virus (HAV) for children of ethnic minorities in Amsterdam.

Background: Pharmaco-economic analysis is relevant for motivating reimbursement of vaccination costs in the framework of a programmatic approach to vaccination of ethnic minorities.

Design: Pharmaco-economic modeling.

The novel somatostatin analog SOM230 is a potent inhibitor of hormone release by growth hormone- and prolactin-secreting pituitary adenomas in vitro.

To determine the inhibitory profile of the novel somatostatin (SRIF) analog SOM230 with broad SRIF receptor binding, we compared the in vitro effects of SOM230, octreotide (OCT), and SRIF-14 on hormone release by cultures of different types of secreting pituitary adenomas. OCT (10 nM) significantly inhibited GH release in seven of nine GH-secreting pituitary adenoma cultures (range, -26 to -73%), SOM230 (10 nM) in eight of nine cultures (range, -22 to -68%), and SRIF-14 (10 nM) in six of six cultures (range, -30 to -75%). The sst analysis showed predominant but variable levels of somatostatin receptor (sst)(2) and sst(5) mRNA expression.

A single-dose comparison of the acute effects between the new somatostatin analog SOM230 and octreotide in acromegalic patients.

Treatment with the somatostatin receptor (sst) subtype 2 predominant analogs octreotide and lanreotide induces clinical and biochemical cure in approximately 65% of acromegalic patients. GH-secreting pituitary adenomas, which are not controlled, also express sst(5). We compared the acute effects of octreotide and SOM230, a new somatostatin analog with high affinity for sst(1,2,3,5) on hormone release in acromegalic patients.

Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades.

Mitogen-activated protein kinase (MAPK) cascades can operate as bistable switches residing in either of two different stable states. MAPK cascades are often embedded in positive feedback loops, which are considered to be a prerequisite for bistable behavior. Here we demonstrate that in the absence of any imposed feedback regulation, bistability and hysteresis can arise solely from a distributive kinetic mechanism of the two-site MAPK phosphorylation and dephosphorylation.

[Shigellosis, a sexually transmitted disease in homosexual men].

A study of the registered number of Shigella infections in Amsterdam for the period 1997-2001 revealed that in 2001, there was an increase in the number of homosexual patients with oral-anal contacts as source for their infections. All of these infections were caused by subtype Shigella sonnei. The infections were not associated with a specific meeting place for homosexual men.

Tyr-317 phosphorylation increases Shc structural rigidity and reduces coupling of domain motions remote from the phosphorylation site as revealed by molecular dynamics simulations.

Activated receptor tyrosine kinases bind the Shc adaptor protein through its N-terminal phosphotyrosine-binding (PTB) and C-terminal Src homology 2 (SH2) domains. After binding, Shc is phosphorylated within the central collagen-homology (CH) linker region on Tyr-317, a residue remote to both the PTB and SH2 domains. Shc phosphorylation plays a pivotal role in the initiation of mitogenic signaling through the Ras/Raf/MEK/ERK pathway, but it is unclear if Tyr-317 phosphorylation affects Shc-receptor interactions through the PTB and SH2 domains.

HIV testing behaviour among heterosexual migrants in Amsterdam.

This cross-sectional study among heterosexual migrant groups in south-eastern Amsterdam, the city area where the largest migrant groups live, provides an insight into HIV testing behaviour in this particular group. Participants were recruited at street locations (May 1997-July 1998) and interviewed using structured questionnaires. They also donated saliva for HIV testing.

Hexokinase II: the integration of energy metabolism and control of apoptosis.

Hexokinase II is often highly expressed in poorly differentiated and rapidly growing tumors that exhibit a high rate of aerobic glycolysis. Hexokinase II binds to the mitochondrial membrane through its interaction with the outer membrane voltage-dependent anion channel (VDAC), preferentially at contact sites between the outer and inner mitochondrial membrane. This location is thought to be important for the integration of glycolysis with mitochondrial energy metabolism.

[HIV-screening among pregnant women in the region of Amsterdam in 2002].

In 2001, the Municipal Health Service started offering HIV tests to all pregnant women in and around Amsterdam. All midwives and all hospitals but one participated in this HIV screening. In 2002, of the 10,752 pregnant women offered HIV testing 13.

Pyelonephritis caused by Actinobaculum schaalii in a child with pyeloureteral junction obstruction.

Reported here is the case of a 5-year old boy with a pyeloureteral junction (PUJ) obstruction and pyelonephritis caused by Actinobaculum schaalii, an Actinomyces-like organism. Pyelonephritis or any other urinary tract infection caused by Actinobaculum schaalii has not been described in children before. The patient responded well to pyeloplasty in combination with antibiotic treatment.

TNF-alpha-induced cell death in ethanol-exposed cells depends on p38 MAPK signaling but is independent of Bid and caspase-8.

Alcoholic liver disease is associated with an increase in the number of necrotic and apoptotic liver parenchymal cells. Part of this injury is mediated by TNF-alpha. Ethanol exposure sensitizes cells to the cytotoxic effects of TNF-alpha.

[Travel advice on the prevention of infectious diseases insufficiently obtained by indigenous and non-native inhabitants of Amsterdam, the Netherlands].

Objective: To determine the travel behaviour of inhabitants of Amsterdam, the Netherlands, with respect to age and ethnicity, as well as the impact of travel advice, in particular regarding hepatitis A vaccination of Turkish and Moroccan children.

Design: Descriptive.

Method: In a sample of 2000 inhabitants of Amsterdam, a survey was carried out during the period October 1999-November 2000 on seeking medical advice prior to travelling.

The role of the specialist physician in nursing homes: the Netherlands' experience.

Background: Dutch nursing homes employ physicians who have completed a two year specialist training programme to become a qualified nursing home physician. This paper describes the origin of the profession of nursing home medicine in the context of Dutch nursing homes.

Method: Review of the history and development of the need for specialist physicians in care of residents in nursing homes.

A Ca2+-induced mitochondrial permeability transition causes complete release of rat liver endonuclease G activity from its exclusive location within the mitochondrial intermembrane space. Identification of a novel endo-exonuclease activity residing within the mitochondrial matrix.

Endonuclease G, a protein historically thought to be involved in mitochondrial DNA (mtDNA) replication, repair, recombination and degradation, has recently been reported to be involved in nuclear DNA degradation during the apoptotic process. As a result, its involvement in mtDNA homeostasis has been called into question and has necessitated detailed analyses of its precise location within the mitochondrion. Data is presented localizing rat liver endonuclease G activity exclusively to the mitochondrial intermembrane space with no activity associated with either the interior face of the inner mitochondrial membrane or with the mitochondrial matrix.