Epoetin alfa and beta differ in their erythropoietin isoform compositions and biological properties.

Epoetin alfa and beta are the two forms of recombinant DNA-derived erythropoietin (rEPO), both synthesized in Chinese hamster ovary cells, which are used for the treatment of erythropoietin (EPO)-responsive anaemias. Several batches of each of these rEPOs were compared for differences in their EPO isoform compositions by isoelectric focusing (IEF) and in a range of lectin-binding assays, and for differences in their EPO activities by in-vivo and in-vitro mouse bioassays and by immunoassay. Epoetin beta was found to differ from epoetin alfa in containing: (a) a greater proportion of more basic isoforms, (b) a greater proportion of EPO binding to Erythrina cristagalli agglutinin (which binds N-glycans with nonsialylated outer Gal beta1-4GlcNAc moieties), and (c) isoforms with higher in-vivo:in-vitro bioactivity ratios. Epoetin beta also contained slightly more than epoetin alfa of EPO binding to Lycopersicon esculentum agglutinin (which binds N-glycans containing repeating Gal beta1-4GlcNAc sequences), to the leucoagglutinin of Phaseolus vulgaris (which binds tetraantennary and 2,6-branched triantennary N-glycans) and to Agaricus bisporus agglutinin (which binds Gal beta1-3GalNAc containing O-glycans). No differences were found between the two rEPOs in their binding to a further five lectins. The differences between the isoform composition of epoetin alfa and beta, and the smaller inter-batch differences appear to be due to differences in glycosylation. The higher murine in-vivo:in-vitro bioactivity ratio of epoetin beta compared to epoetin alfa could not be explained in terms of differences in their degrees of sialylation, but was consistent with differences in their pharmacokinetics and pharmacodynamics observed in human subjects. There have been no reports that epoetin alfa differs from epoetin beta in its clinical efficacy, but the differences between epoetin alfa and beta in some analytical systems suggest that there might be a need for separate international standards for these two types of rEPO.

Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism.

To assess the possibility that lipopolysaccharide (LPS) induces sickness behaviour by activating primary afferent nerves, the effects of LPS (1.25 mg kg-1, intraperitoneally) were compared in vagotomized and sham-operated rats. Subdiaphragmatic vagotomy blocked the LPS-induced depression of social investigation but had no effect on LPS-induced increases in levels of IL-1 beta in plasma and peritoneal macrophages and on LPS-induced changes in dehydrogenase activity of peritoneal macrophages.

Solid phase enzyme immunoassays for the quantification of serum amyloid P (SAP) and complement component 3 (C3) proteins in acute-phase mouse sera.

Simple, reliable and sensitive enzyme immunoassays have been developed for the quantification of the mouse acute-phase SAP and C3 proteins. The ELISA systems were validated using sera from mice injected with S. dysenteriae endotoxin, and detected 500 pg protein/ml. The assays use 96-well microtitre plates permitting rapid processing of a large number of samples.

The use of clearplan home ovulation detection kits in unexplained and male factor infertility.

One hundred and five couples with unexplained infertility and 43 couples whose infertility was thought to be due to reduced sperm motility were recruited. The median duration of infertility was 36 months (range 12-168). Couples were randomly allocated to either using Clearplan home ovulation detection kits for 3 cycles or were advised about the optimal time during their menstrual cycle to achieve a pregnancy. The clinical details of the 2 groups were similar. In couples with unexplained infertility over the study period 10 (20.4%) in the Clearplan group and 9 (16%) in the control group conceived with 58% of pregnancies occurring in the first cycle. In couples with reduced sperm motility, the results were disappointing with only 2 (8%) pregnancies in the Clearplan group and 2 (11.1%) in the controls. Assisted reproduction technology may not be justified as the first line of management in patients with unexplained infertility.

The clinical value of Clearplan home ovulation detection kits in infertility practice.

A home ovulation testing kit, Clearplan, that detects the urinary luteinizing hormone (LH) surge was used by 32 patients on a donor insemination programme for 50 cycles to indicate when to first attend the clinic for a serum LH test to determine ovulation. Using Clearplan significantly reduced the number of clinic attendances (4.06 +/- 1.5) compared to the preceding control cycle (7.06 +/- 2.0 p less than 0.001). One serum LH peak was missed using Clearplan. Ovulation was predicted within 2 days of the serum LH surge in 77% of cycles. Home ovulation determination has the potential to reduce the stress and cost of fertility programmes.

Control units for operation of computers by severely physically handicapped persons.

For those severely physically disabled persons who are unable to use keyboards, the computer has to be adapted to operate from the limited signals that can be obtained from controlled movements. These movements need to be identified and appropriate devices provided which can produce suitable signals to operate a computer. To minimize programming effort, it is also necessary to standardize on a particular form of input signal-in our case, one or two on/off contacts-for which the programs are developed. It is desirable for user input devices to be linked to the computer through an Interface Control Unit, which can also be operated from a remote infra-red unit mounted on a wheelchair. Such units are described.

Effect of bacterial endotoxin on body temperature, plasma zinc and plasma concentrations of the acute-phase protein serum amyloid p component in mice.

Bacterial endotoxin and lipid A evoked dose-dependent increases in body temperature and plasma SAP concentrations and dose-dependent falls in plasma zinc concentrations in mice. The respective sensitivities of the three variables to lipid A or to whole endotoxin had the relation SAP greater than Zinc much greater than body temperature; zinc and SAP responses were evoked by less than 1 ng lipid A/endotoxin. Pretreatment with indomethacin prevented only the temperature response to lipid A. Pretreatment with dexamethasone did not affect the temperature response but diminished the zinc response and enhanced the SAP response to lipid A.

The transfer of selected image data to a computer using a conductive tablet.

The processing and analysis of images in a computer often requires the selection of particular features of a complex image for more detailed study. Sometimes such decisions are empirical, in which case it would be extremely difficult to describe a rigorous algorithm for detecting these features automatically in a computer. In this situation graphic tablets can be very useful as they allow an operator to use experience in deciding which features are to be transferred into a computer. A tablet is described which uses a conductive glass plate and pencil probe. A number of subroutines are available in a general purpose program for conventional processing, calculation and displays to be effected by simple option selection on the tablet for specific applications in cell growth, modeling and three dimensional reconstruction of serial sections, special programs were developed which could include appropriate subroutines. The categorisation of subsections by an operator was particularly useful in allowing different methods of analysis and display to be applied to each. For example they could be displayed separately or given different dentisy levels by choosing the appropriate option in the program.