Regulation of T cell activation in vitro and in vivo by targeting the OX40-OX40 ligand interaction: amelioration of ongoing inflammatory bowel disease with an OX40-IgG fusion protein, but not with an OX40 ligand-IgG fusion protein.

OX40 is a member of the TNFR superfamily, and is found predominantly on activated CD4-positive T cells. In vitro an OX40-IgG fusion protein inhibits mitogen- and Ag-driven proliferation and cytokine release by splenocytes and lymph node T cells. In contrast, an OX40 ligand-IgG fusion protein enhanced proliferative responses. In normal mice, OX40-positive cells are observed only in lymphoid tissues, including Peyer's patches of the gut. In mice with hapten-induced colitis or IL-2 knockout mice with spontaneous colitis, OX40-positive cells are found infiltrating the lamina propria. Administration of the OX40-IgG fusion protein to mice with ongoing colitis (but not the OX40 ligand-IgG) ameliorated disease in both mouse models of inflammatory bowel disease. This was evidenced by a reduction in tissue myeloperoxidase; reduced transcripts for TNF-alpha, IL-1, IL-12, and IFN-gamma; and a reduction in the T cell infiltrate. Targeting OX40 therefore shows considerable promise as a new strategy to inhibit ongoing T cell reactions in the gut.

The effects of frequent ejaculation on seminal spermatozoal number and calculation of daily spermatozoal output.

Spermatozoal depletion of the extra-gonadal reserve (EGR) has been monitored in 14 men by analysing ejaculates collected daily for 5 days. It has been concluded that EGR is stabilized within 2 days and that an estimate of daily spermatozoal output can be obtained either by averaging the values from days 3 to 5 or by using the day 5 value alone. This latter parameter may prove useful clinically.

Some attitudes to artificial insemination by donor.

A preliminary survey to assess and quantify attitudes to Artificial Insemination by Donor (AID) has been conducted with the aid of an article in a national magazine. The consensus of 375 individuals (mostly with a vested interest in infertility) concerning their attitudes to semen donation, hypothetical receipt of donor semen, legal aspects and the keeping of donor records, etc., have been analysed and their answers correlated to their age, sex, ethnic grouping, educational level, religion, and marital and fertility status as well as their place of residence. Within the limitations of this study, three major conclusions can be drawn. Firstly there are probably many potential semen donors in the general community and recruitment techniques need to be improved to capitalize on this source. Secondly, a centralized non-identifying National Register of donor information may be tolerated, and finally, the couples questioned felt an AID child should not be likened to one received through adoption. These and other findings would suggest that attitudes towards AID are changing and consequently some of the practices within AID programmes may need to be altered. Further statistically conducted surveys are warranted to determine these current attitudes.

Studies of human seminal parameters with frequent ejaculation. I. Clinical characteristics.

The intra-subject variation in seminal parameters (e.g. volume; spermatozoal density, motility and normal morphology, and total spermatozoal count) have been examined in 172 men following a set ejaculatory pattern designed to exhaust their extra-gonadal spermatozoal reserve. The results have demonstrated that the motility and normal morphology of spermatozoa do not change significantly with ejaculation frequency. Also, while the volume of the ejaculate and the total number of spermatozoa decreased during a period of frequent coitus, an individual's depletion and recovery of his spermatozoal reserve could not be accurately predicted. It is suggested that coital frequency during the woman's periovulatory period could be modified by the partner's response to this test. Furthermore, while it is acknowledged that the variation in results from a 'routine' semen analysis is large, data obtained after depletion of the extra-gonadal reserve and recovery over a set time may have more value and could be the method of choice for the future.

Studies of human seminal parameters with frequent ejaculation II. Spermatozoal vitality and storage.

The hypothesis that the percentage of dead spermatozoa in an ejaculate is related to their storage time in the extra-gonadal reserve was tested using a protocol where men followed a set ejaculatory pattern. Semen samples were requested as follows: abstinence from ejaculation for at least 3 days (not more than 7 days) followed by production of the first sample, then one ejaculation per day for 4 consecutive days before the second sample; and, lastly, abstinence for a further 4 days and production of the final sample. Within the time scale of the experiment there was no relationship between the percentage of dead spermatozoa in the ejaculate and the preceding period of abstinence, nor was the percentage of dead spermatozoa related to the total number of spermatozoa present. The percentage of non-motile, but vital, spermatozoa similarly exhibited a random pattern. Thus whatever mechanisms are contributing to the mortality of spermatozoa, they are independent of storage time in the extra-gonadal reserve, and total spermatozoal count. Therefore, in the absence of necrozoospermia, this parameter probably contributes little to the overall diagnosis of infertility, but does allow assessment of the functional spermatozoa present.