[Environmental regulations impede cancer research and treatment].

In order to legally conduct clinical research into new cancer treatments with medicinal products based on genetically modified organisms (GMOs) and treat cancer patients with these products, Dutch hospitals must obtain an environmental permit from the Minister of Infrastructure & Water Management. In the Netherlands, permit applications are assessed more strictly than in other EU member states, even if the products do not pose any real risk to the population and the environment. As a result, Dutch patients have to wait longer before the clinical trial or therapy with these GMO products can commence.

[GIP-like findings with a special spectrum of causes].

Giant cell interstitial pneumonia (GIP)-like pulmonary alterations as a special form of condensate pneumopathy may result following inhalation of certain types of tobacco smoke which can cause a pitfall diagnosis of sideropneumoconiosis or hard metal lung disease. Exact information regarding the patient occupation and smoking history and especially regarding the origin of the cigarettes helps to clarify the findings.

[Patient safety in clinical intervention research].

In clinical intervention research, the monitoring of patient safety is essential. In December 2009, a symposium on the role of the different parties involved was organised. Research starts with a robust protocol with a section dealing with interim decision-making and procedures for reporting during the research.

Combined adaptive servo-ventilation and automatic positive airway pressure (anticyclic modulated ventilation) in co-existing obstructive and central sleep apnea syndrome and periodic breathing.

Background: The co-existence of obstructive and central sleep apnea/hypopnea syndrome (OSAS) and periodic breathing is common in patients with and without underlying heart diseases. While automatic continuous positive airway pressure (APAP) has proven to effectively treat OSAS, the adaptive servo-ventilation (ASV) sufficiently improves periodic breathing. This is the first trial on a device which combines both treatment modes.

[Evaluation of a new automatic CPAP algorithm in the treatment of obstructive sleep apnoea syndrome].

Background: Automatic continuous positive airway pressure (automatic CPAP, APAP) is an effective treatment option in the obstructive sleep apnoea syndrome (OSAS). The differentiation of obstructive and central respiratory events is crucial in adjusting the optimal pressure in this treatment mode. In this pilot study we evaluated a new automatic CPAP algorithm in OSAS patients.

Legislation and review of medical research with minors in The Netherlands.

In The Netherlands medical research with minors is regulated in the Medical Research Involving Human Subjects Act. During the legislation process in the Houses of Parliament in the 1990s the issue of nontherapeutic research with minors and incapacitated subjects was heavily debated. Stringent regulations were formulated for this type of research and the Act became operational in December 1999.

[Time for professionalising the system of medical ethics review in the Netherlands].

In two recent papers, a radical change of the review system for medical ethics review committees was proposed. The current systems in Great Britain and Australia were described and it was suggested that the extended roles and responsibilities of the medical ethics review committees could not be fulfilled by the present committees. It was proposed that professional medical ethics committees be established with full time members who would receive an appropriate honorarium.

Recycling MHC class I molecules and endosomal peptide loading.

MHC class I molecules usually present peptides derived from endogenous antigens that are bound in the endoplasmic reticulum. Loading of exogenous antigens on class I molecules, e.g.

Canine distemper virus from diseased large felids: biological properties and phylogenetic relationships.

Specific pathogen free (SPF) domestic cats were inoculated with tissue homogenate obtained from a Chinese leopard (Panthera pardus japonensis) that had died in a North American zoo from a natural infection with canine distemper virus (CDV). The cats developed a transient cell-associated CDV viraemia along with pronounced lymphopenia but did not show any clinical symptoms. Plasma neutralizing-antibody titres against the homologous CDV (A92-27/4, isolated from the Chinese leopard) were consistently higher than against the CDV vaccine strain 'Bussell'.

Morbillivirus infections of aquatic mammals: newly identified members of the genus.

Several disease outbreaks, which have caused the deaths of many thousands of seals and dolphins during the last decade, have now been attributed to infections with newly identified Morbilliviruses. Outbreaks in the late eighties amongst harbour seals (Phoca vitulina) and grey seals (Halichoerus grypus) in northwestern Europe and amongst baikal seals (Phoca sibirica) in Siberia were caused by the newly discovered phocine distemper virus and by a strain of canine distemper virus, respectively. Although closely related these two viruses were not identical.

Phylogenetic evidence of canine distemper virus in Serengeti's lions.

Recently an epizootic, reported to be due to a morbillivirus infection, affected the lion population of the Tanzanian Serengeti National Park. A morbillivirus phosphoprotein (P) gene fragment was amplified by PCR from tissue samples of several affected lions. Sequencing of the amplificates and subsequent phylogenetic analyses revealed that a wild-type strain of canine distemper morbillivirus (CDV) was involved.

Allelic diversity at the Mhc-DP locus in rhesus macaques (Macaca mulatta).

Allelic diversity at the major histocompatibility complex class II DP locus of rhesus macaques was studied by sequencing exon 2 of Mamu-DPA1 and -DPB1 genes. The Mamu-DPA1 gene is apparently invariant, whereas the Mamu-DPB1 locus displays polymorphism. Here we report the characterization of 1 Mamu-DPA1 and 13 Mamu-DPB1 alleles which were compared with other available primate Mhc-DPA1 and -DPB1 sequences.

Insertion of N-linked glycosylation sites in the variable regions of the human immunodeficiency virus type 1 surface glycoprotein through AAT triplet reiteration.

Variable regions with sequence length variation in the human immunodeficiency virus type 1 envelope exhibit an unusual pattern of codon usage with AAT, ACT, and AGT together composing > 70% of all codons used. We postulate that this distribution is caused by insertion of AAT triplets followed by point mutations and selection. Accumulation of the encoded amino acids (asparagine, serine, and threonine) leads to the creation of new N-linked glycosylation sites, which helps the virus to escape from the immune pressure exerted by virus-neutralizing antibodies.

Comparative analysis of the gene encoding the nucleocapsid protein of dolphin morbillivirus reveals its distant evolutionary relationship to measles virus and ruminant morbilliviruses.

A morbillivirus of uncertain origin recently killed hundreds of Mediterranean dolphins. This is the first report of the nucleotide and deduced amino acid sequence of a dolphin morbillivirus (DMV) gene. The sequence of the nucleocapsid (N) gene including boundaries was determined.

A subset of HLA-B27 molecules contains peptides much longer than nonamers.

An unusual monoclonal antibody (MARB4) directed against HLA-B27 that reacts with only approximately 5-20% of the cell surface HLA-B27 was used for large-scale purification of these molecules. Subsequent mass spectrometry of HLA-B27-bound peptides showed that the minor MARB4-reactive population contained peptides primarily from 900 to 4000 Da in size (approximately 8-33 amino acid residues), whereas the major HLA-B27 population contained peptides in the mass range of 900-1400 Da (approximately 8-12 amino acid residues). Thus, a subset of HLA-B27 molecules binds to peptides much longer than nonamers.

Fusion protein gene nucleotide sequence similarities, shared antigenic sites and phylogenetic analysis suggest that phocid distemper virus type 2 and canine distemper virus belong to the same virus entity.

Nucleotide sequencing of the fusion protein (F) gene of phocid distemper virus-2 (PDV-2), recently isolated from Baikal seals (Phoca sibirica), revealed an open reading frame (nucleotides 84 to 2075) with two potential in-frame ATG translation initiation codons. We suggest that the second in-frame ATG triplet at positions 264 to 266 initiates the translation, resulting in a protein of 537 amino acid residues with a calculated M(r) of 63,035. The putative F1/F2 cleavage site, located approximately 100 amino acid residues from the N terminus, is identical to those of the F proteins of phocid distemper virus-1 (PDV-1) isolated from European harbour seals (Phoca vitulina) and of canine distemper virus (CDV).

Mhc-DRB and -DQA1 nucleotide sequences of three lowland gorillas. Implications for the evolution of primate Mhc class II haplotypes.

Mhc-DRB and -DQA1 second-exon and -DRB 3'-untranslated-region nucleotide sequences of three lowland gorillas with no known family relationship with each other and of two HLA homozygous typing cell lines were determined and compared with published primate Mhc-DRB and -DQA1 sequences. Eleven distinct MhcGogo-DRB second-exon sequences were found, which represent the gorilla counterparts of the HLA-DRB1*03, -DRB1*10, -DRB3, -DRB5, and -DRB6 allelic lineages. One Gogo-DRB second-exon sequence does not have an obvious human counterpart and is tentatively designated Gogo-DRBY*01.