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Biomedical subjects

M Elder

Publications and source records attributed to M Elder.

29 records · Page 2Linked to original sources

Thymosin and the spontaneously diabetic BB rat.

The biological basis for autoimmunity and immunoincompetence in the BB rat has yet to be localized. In spite of normal thymic histology, thymocyte subsets and blastogenesis, thymus gland products (thymosins) have yet to be studied. In the present report, thymus gland function was studied by measuring thymosin alpha 1 levels at one time point in the BB rat compared with control rates, and BB rat responses to exogenous thymosin (Thymosin fraction 5) were observed. At five months of age, BB rats had thymosin alpha 1 levels comparable to Lewis and Wistar furth rats. Thymosin fraction 5 increased the ratio of peripheral blood W3/25 positive to OX8 positive cells, but otherwise had no effect on the BB rats' T-cell immunodeficiency, or frequencies of tissue autoantibodies or insulin-dependent diabetes. Although B-lymphocyte counts were normal in BB rats, splenocyte responses to B-lymphocyte mitogens were depressed. However, thymosin fraction 5 improved the BB rat B-lymphocyte blastogenesis to near normal for Mycoplasma neurolyticum. Coupled with our previous work, our results suggest that the immune derangement in the BB rat resides outside the thymus.

Animals↗

Pharmacokinetics of different doses of norethisterone oenanthate.

Doses of norethisterone oenanthate of 300, 150, 100 and 50 mg were administered to four groups of subjects. Due to wide intersubject variations there were no statistically significant differences in the pharmacokinetic parameters for the different groups but there were significant correlations between the dose and the mean values for these parameters. There was little difference between the groups in the duration for which ovarian function was suppressed due to the inter-subject variation being greater than the inter-dose effect. The duration of the antifertility action of norethisterone oenanthate cannot be increased by increasing the dose above the standard 200 mg; however, with an injection interval of 60 to 70 days, it seems likely that the dose could be reduced to 150 mg.

Adult↗

Gastric parietal cell and other autoantibodies in the BB rat.

A longitudinal study of circulating autoantibodies in the sera of 48 BB rats was performed by indirect immunofluorescence. No pancreatic islet cell, adrenocortical, or thyroid microsomal autoantibodies were found. However, autoantibodies reactive to gastric parietal cells (PCA), smooth muscle, and thyroid colloidal antigens were identified, PCA were not detected in Wistar-Furth or BB x Wistar-Furth F1 hybrid rats. The range of ages at the time of first appearance of PCA was the same as that of onset of insulin-dependent diabetes (IDD) in the BB rats, suggesting that the processes leading to PCA and IDD were occurring at the same time of life in these animals. The presence of PCA was associated with degrees of lymphocytic gastritis and with squamous metaplasia of the gastric mucosa in the oldest BB rats (9 mo of age). Levels of serum iron and vitamin B12 did not differ between PCA-positive and PCA-negative BB rats, nor was achiorhydria found in any rat studied. The identification of PCA (and chronic gastritis) and other autoantibodies in the BB rat suggests that these animals have an underlying autoimmune diathesis. These findings thus provide indirect support for an autoimmune pathogenesis for IDD in the BB rat.

Achlorhydria↗

Pharmacokinetics of norethisterone oenanthate in humans.

The pharmacokinetics of a dose of 200 mg NET-OEN were studied after intramuscular injection into nine subjects. Blood levels of NET and NET-OEN increased rapidly, reaching peaks in most subjects within seven days. At all times after injection, serum levels of NET exceeded those of NET-OEN. The half-life of absorption varied from 5.4 to 22.3 days and the half-life of elimination varied from 7.5 to 22.5 days; there was a significant correlation (R = 0.78) between these two half-lives. There were significant correlations between the absorption half-lives and the peak values of NET and NET-OEN, the time to reach peak values and the time for which NET was detectable in serum. In all subjects NET was detectable in the circulation for a longer time after injection (mean value 74 days) than NET-OEN (mean value 43 days). The time for which the two steroids were detectable in the circulation showed a significant correlation with the elimination half-lives but there was no correlation with the peak values attained, the time taken to reach peak values and bioavailability. There was a two-fold variation between the subjects in the bioavailability of NET, less than 5% of the bioavailable NET was released after day 60.

Absorption↗

Gonadal autoantibodies in patients with hypogonadism and/or Addison's disease.

The sera from 325 normal individuals, 21 patients with Turner's syndrome, 505 patients with insulin-dependent diabetes mellitus, 15 patients with unexplained ovarian insufficiency, and 37 patients with Addison's disease or serological evidence of adrenal autoimmunity were examined for the presence of gonadal autoantibodies by an indirect immunofluorescent technique using sections of human testis. All 12 patients found to have gonadal autoantibodies also had adrenocortical autoantibodies. These autoantibodies were completely absorbed with powdered adrenal cortex and thus were "steroidal cell" antibodies (SCA), cross-reactive with a cytosolic antigen in the steroid-producing cells of adrenal cortex, placental syncytiotrophoblast, Leydig areas of testis, and theca interna/granulosa layer of ovarian follicles. Sera with SCA had reduced titers of adrenal antibodies after repeated absorptions with gonadal or placental tissues, suggesting that adrenal-specific autoantibodies were also present. Sera from patients with only adrenal antibodies had no significant changes in antibody titers after repeated absorptions with gonadal or placental tissues. In conclusion, all gonadal autoantibodies found were SCA. SCA were only found in patients with adrenal autoimmunity, many of whom had hypogonadism. In other patients or in normal individuals, the existence of SCA or gonadal autoimmunity in the absence of adrenocortical autoantibodies must be rare.

Addison Disease↗

Occurrence of ovulation in women receiving the injectable contraceptive norethisterone oenanthate.

Ovarian function was studied in ten women receiving a single intramuscular injection of 200 mg norethisterone oenanthate. Two of the ten women appeared to ovulate within 60 days of injection and a further four within 90 days. Follicular activity probably not followed by ovulation occurred in five subjects within 60 days of the injection and in a further subject within 90 days. Only one subject showed no evidence of follicular or luteal activity during the course of this study. There was wide variation in the rate at which the administered gestagen was metabolised and no correlation between the rate of metabolism of norethisterone and the return of ovarian function or the ponderal index, height or weight of the subjects.

Adult↗

Millisecond X-ray diffraction and the first electron density map from Laue photographs of a protein crystal.

Attempts to use X-ray crystallography to extract three-dimensional information on transient phenomena in crystals have been hampered primarily by long data collection times. Here we report on the first difference Fourier map obtained from Laue diffraction photographs of a protein crystal, glycogen phosphorylase b. Data collection time was 3 s using the high-intensity white X-radiation generated on the wiggler magnet of the Daresbury Synchrotron Radiation Source (SRS), but data acquisition in the millisecond-submillisecond range is possible. The method presented here uses a simple difference technique and was designed to analyse structural changes relative to a known starting structure. The combination of this approach with cine techniques allows the recording of three-dimensional motion pictures at atomic resolution and opens up new areas in structural biology and chemistry.

Electrons↗