Plain English summaryThis commentary talks about patient involvement in one of the biggest EU projects to date—U-BIOPRED. It describes how people and carers of people with asthma have been able to develop and drive their input and have their voice heard among the >200 healthcare professional project members.Five key principles for the success of the patient involvement group are presented: involve early, involve deeply, have patients feedback on project progress, include patients in dissemination and help patients convey their own story.This group has been used as an example for other EU-funded projects, and the patient involvement group will be maintained after the end of the project to ensure that their experience and knowledge can help develop best practice in the future.

Hormone sensitivity, as indicated by the presence of steroid hormone receptors and by the effect of androgens and anti-androgens on the release of proteins by cultured cells of the human prostate tumor cell line lymph node carcinoma of the prostate-fast growing colony (LNCaP-FGC), has been studied. The growth of the LNCaP-FGC cells were stimulated by androgens in a dose-dependent way. Under optimal conditions the synthetic nonmetabolizable androgen 17 beta-hydroxy-17 alpha-methyl-(3H)-estra-4,9,11-trien-3-one (R1881) (0.1 nM) stimulated cell growth by approximately 2.3 times. Increasing doses of R1881 (1-100 nM) partly decreased the stimulation of the cell growth. The anti-androgen cyproterone acetate exerted inhibitory effects on cell growth. The nuclear extract of the LNCaP-FGC cells contained 17,000 +/- 2,500 (mean +/- SD) KCl-extractable, nuclear androgen receptor sites/cell. Estrogen and progesterone receptors were not detectable in the nuclear extracts nor in cytosol, indicating that these receptors were absent. The release of proteins in the culture medium was studied using incorporation of the 35S-methionine, sodium dodecyl sulfate (SDS)-gel electrophoresis, and fluorography. Cells grown in media containing charcoal-stripped fetal calf serum released significantly lower amounts of a protein with an apparent molecular mass of 42,000 daltons. The release of this 42-kD protein could be restored in cells cultured in the presence of 5 alpha-dihydrotestosterone (0.1-1 microM) or R1881 (0.1-100 nM), whereas the addition of estrogens or corticosteroids had no effect. In the presence of anti-androgens, such as cyproterone acetate and 5,5-dimethyl-3-(4-nitro-3-(trifluoro-methyl)-phenyl)-2,4-imidasolidin edione, inhibitory effects on the release of the 42-kD protein were observed. The observed parallel between the effects of (anti)-androgens on the growth of the LNCaP prostate cells and the release of the 42-kD protein suggests that this protein is involved in the regulation of malignant prostate cell growth.

Follicle stimulating hormone (FSH) is a heterodimeric glycoprotein hormone produced in the anterior pituitary gland. The hormone is essential in the regulation of reproductive processes, such as follicular development and ovulation. It is clinically used for treatment of anovulation and in assisted reproduction technologies such as in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Until recently, the only source for human FSH has been the urine from post-menopausal women. Such a natural source implies limited availability and potential product variability. Thus, we have cloned the genes encoding the alpha- and beta-subunits of human FSH and transfected these into Chinese hamster ovary (CHO) cells. A CHO-clone was isolated capable of secreting intact glycosylated FSH with identical amino acid sequences to natural FSH. This cell line was grown in perfusion culture and enabled us to isolate highly pure FSH (> 99%). The complexity of the charge distribution of human recombinant FSH was demonstrated by Isoelectric focusing. The observed microheterogeneity is caused by the large number of carbohydrate chain structures which are added to the four potential glycosylation sites in the alpha beta-dimer. Furthermore, the carbohydrates show a variation in their degree of sialylation which reflects the different pl values of the individual isohormones. Despite the complexity of post-translational modification, the isoform distribution of recombinant FSH produced in a CHO-cell line and grown in perfusion culture is surprisingly similar to that observed with pituitary FSH and urinary FSH. In conclusion, we have shown that FSH-gene transfected CHO-cells are capable of stable serum-free production of recombinant FSH. A process has been developed which assures the consistent and reproducible production of highly-purified recombinant FSH.

This paper summarises the results of a major revision of the data underlying a previous study of Britain's productivity position in an international perspective (O'Mahony, 1999). Thus it examines the productivity record of the UK relative to the US, France, and Germany. There have been a number of changes since the original study which necessitated a revision rather than a mere updating of previous estimates. These included changes to national accounts definitions of value added to include immaterial investments following the adoption of SNA93 by these countries, labour input revisions which allow the distinction between jobs and persons employed, extensive revisions to industrial classifications and the desire to present estimates for unified Germany rather than the former West Germany. In addition the data series were extended to include a division of capital stocks by asset type which allows for a more refined treatment of capital input in explaining relative labour productivity performance. Hence the first aim of this paper is to see if these changes have significantly altered perceptions of Britain's relative productivity position. The evidence on the extent to which Britain has improved its relative productivity position in the past decade is presented and the paper re-examines the issue of the impact of its investment record in both physical and human capital on Britain's labour productivity shortfall. Since the publication of the original study, much of the productivity literature has focused on the new economy and, in particular, the impact of information and communications technology (ICT) on productivity trends. The association between ICT and sector productivity growth rates is also considered below.

Biologically active recombinant human follitropin has been expressed in Chinese hamster ovary cells. The carbohydrate chains of the recombinant glycoprotein hormone were enzymatically released by peptide-N4-(Nacetyl-p-glucosaminy1)asparagine amidase F. The oligosaccharides were separated from the N-deglycosylated protein by gel-permeation chromatography on Bio-Gel P-100, and fractionated by a combination of FPLC on Mono Q and HPLC on Lichrosorb-NH,. The structures of the carbohydrate chains were determined by 500-or 600-MHz 'H-NMR spectroscopy. The following types of carbohydrates occur: monosialylated diantennary (lo%), disialylated diantennary (43 YO), disialylated tri-antennary (5%), trisialylated tri-antennary (1 3%), trisialylated tri'-antennary (So/,), and tetrasialylated tetraantennary (1 2%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively a2-3-linked N-acetylneuraminic acid (Neu5Ac). Previously, for pituitary follitropin mono-, di-, tri-, tri'-, and tetra-antennary oligosaccharides containing a2-3-as well as a2-6-linked Neu5Ac residues were reported. The bisecting GlcNAc residues present in native follitropin were not detected in the recombinant glycoprotein. Of the oligosaccharides 29% have an al-6-linked Fuc residue at the asparagine-bound GlcNAc, whereas this amount is about 50% in pituitary follitropin. In some of the tri-, tri'-and tetra-antennary oligosaccharide fractions small amounts (< 5%) of compounds were detected having one or more additional Nacetyllactosamine units.Follitropin (follicle-stimulating hormone, FSH) belongs to a heterodimeric glycoprotein hormone family in which each hormone is composed of two non-covalently linked subunits, denoted a and / 3. The amino acid sequences of the a subunits are essentially identical, whereas those of the fl subunits are hormone-specific. The structures of the carbohydrate chains differ between the glycoprotein hormones and are believed to confer hormone specific-functions [l -31.FSH is synthesized by the gonadotropes in the anterior pituitary and is required for normal reproductive functioning in both females and males. There is a need of FSH for clinical purposes since it is applied, either alone or in combination with human LH, for controlled ovarian hyperstimulation in in vitro fertilization [4,5]. Human FSH is also used to stimulate the development of ovarian follicles in anovulatory women suffering from luteal phase deficiency [6], or chronic anovulatory syndrome [7].Correspondence to J. F. G. Vliegenthart, Bijvoet Center, Department of Bio-Organic Chemistry, Utrecht University, Transitorium 111, P. 0. Box 80.075, NL-3508 TB Utrecht, The NetherlandsAbbreviations. PNGase-F, peptide-N4-(N-acetyl-P-glucosaminy1)asparagine amidase F ; NeuSAc, N-acetylneuraminic acid; Fuc, Lfucose; hFSH, human follicle-stimulating hormone (follitropin); LH, luteinizing hormone (lutropin); hCG, human chorionic gonadotropin; CHO, Chinese hamster ovary; t-PA, tissue plasminogen activator.Enzymes. Peptide-N4-(N-acetyl-~-glucosaminyl)asparagine a...