Abstract. The biological properties of different forms of human pituitary FSH, varying in their molecular charge, were investigated. FSH in two individual human pituitaries and a pool of 30 human pituitaries was extracted and subjected to electrophoresis. From each electrophoresis 14 consecutive fractions with the highest RIA activity were examined with in vitro and in vivo bioassays. The in vitro assay was based upon the estimation of oestradiol produced by cultured Sertoli cells from 10 day old rats. The in vivo bioassay was an hCG augmented test using immature female mice injected on 3 consecutive days. The increase in ovarian weight was the index of response. Both in the individual and in the pooled pituitary material the less negatively charged forms had the highest activity in the in vitro bioassay. In contrast, the more negatively charged forms had the highest activity in the in vivo bioassay. Forms of FSH from each of the two individual pituitary extracts were pooled according to their migration rate and injected iv into mice. The amount of FSH remaining in the circulation of the mouse after 1 h was related to the molecular charge. The highest value was obtained with the pool containing the more negatively charged forms of the hormone. The results indicate that the disappearance rate of the FSH molecule is a dominant factor in the in vivo bioassay. A consequence of these observations will be that the assay method chosen to monitor the purification of FSH will have a major influence on the biological properties of the final preparation.
IntroductionThe International Carotid Stenting Study (ICSS, ISRCTN25337470) randomized patients with recently symptomatic carotid artery stenosis > 50% to carotid artery stenting (CAS) or endarterectomy. CAS increased the risk of new brain lesions visible on diffusion-weighted magnetic resonance imaging (DWI-MRI) more than endarterectomy in the ICSS-MRI Substudy. The predictors of new post-stenting DWI lesions were assessed in these patients.MethodsICSS-MRI Substudy patients allocated to CAS were studied. Baseline or pre-stenting catheter angiograms were rated to determine carotid anatomy. Baseline patient demographics and the influence of plaque length, plaque morphology, internal carotid angulation, and external or common carotid atheroma were examined in negative binomial regression models.ResultsA total of 115 patients (70% male, average age 70.4) were included; 50.4% had at least one new DWI-MRI-positive lesion following CAS. Independent risk factors increasing the number of new lesions were a left-sided stenosis (incidence risk ratio [IRR] 1.59, 95% CI 1.04–2.44, p = .03), age (IRR 2.10 per 10-year increase in age, 95% CI 1.61–2.74, p < .01), male sex (IRR 2.83, 95% CI 1.72–4.67, p < .01), hypertension (IRR 2.04, 95% CI 1.25–3.33, p < .01) and absence of cardiac failure (IRR 6.58, 95% CI 1.23–35.07, p = .03). None of the carotid anatomical features significantly influenced the number of post-procedure lesions.ConclusionCarotid anatomy seen on pre-stenting catheter angiography did not predict of the number of ischaemic brain lesions following CAS.
The possible existence of qualitative differences between FSH in pituitaries from men and women of different ages was investigated with the use of an in vitro bioassay, an in vitro bioassay, and a RIA. Aqueous extracts were made from pituitaries obtained at autopsy and frozen until extracted. The FSH activities per pituitary and the ratios of FSH activities as obtained with the three assay methods were similar for young and elderly men. The ratios of in vivo biological to in vitro biological FSH activities were similar for men and postmenopausal women and significantly higher than the corresponding ratio for FSH from young women. With the in vivo bioassay the activity in the extracts of pituitaries from men and young women were similar, whereas extracts from postmenopausal women had significantly higher activity. With the in vitro bioassay the extracts from young women and elderly women had a similar content of FSH activity, whereas the FSH level in the extracts of male pituitaries was significantly lower. The results of the RIA correlated well with those of the in vitro bioassay. In conclusion, the results show that FSH in pituitaries from young women has a biological activity that is qualitatively different from FSH of men and elderly women. The relatively low in vivo biological activity of FSH from young women compared to FSH from men and elderly women was most likely due to a more rapid clearance of the hormone from the circulation of the test animal.
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