Follicle-stimulating hormone blocks estrogen-positive feedback during the early follicular phase in monkeys

Normally cycling rhesus monkeys were treated with 12.5 IU of follicle-stimulating hormone (FSH; n = 9) or saline (n = 9) on cycle days 1 to 4, 1 to 6, or 1 to 8 and 50 micrograms/kg estradiol benzoate (E2B, intramuscularly) on day 1, 3, or 5, respectively. Blood was collected daily, then every 8 hours for 96 hours after E2B treatment. Serum was assayed for FSH and luteinizing hormone (LH) by radioimmunoassay. Laparoscopy and serum E2 levels were used to assess ovarian follicular development. Eight of nine FSH-treated monkeys failed to demonstrate typical LH surges in response to E2B. One monkey treated with E2B on day 1 had an attenuated LH surge. All nine control monkeys demonstrated typical threefold LH increases within 72 hours after E2B treatment. Supraphysiologic ovarian stimulation was not visibly evident until 5 days after initiation of FSH treatment. These results suggest that the FSH-induced blockade of estrogen-positive feedback for the LH surge antecedes overt ovarian hyperstimulation.     

Ovulation induction using "pure" follicle-stimulating hormone in monkeys

Recently we have demonstrated that administration of a "pure" follicle-stimulating hormone (FSH) preparation (Urofollitropin, Serono Laboratories, Inc., Randolph, MA) to normally cycling monkeys induces multiple follicular development. In these earlier studies, a spontaneous luteinizing hormone (LH) surge was uncommon; no attempt was made to induce ovulation with exogenous human chorionic gonadotropin (hCG). In this study, multiple follicular development and ovulation were induced in normally cycling monkeys by daily follicular phase administration of "pure" FSH followed by hCG. Short-term administration of "pure" FSH during the early or late follicular phase also induced multiple follicular development; however, multiple ovulations subsequent to a spontaneous LH surge never occurred. One monkey treated in the late follicular phase did demonstrate a spontaneous LH surge and single ovulation following late follicular phase FSH treatment. These findings suggest that administration of "pure" FSH alone, to enhance the natural ovarian cycle, may be useful for inducing multiple follicular development, but that ovulatory competence is usually dependent on exogenous LH/hCG.     

Cystic adventitial disease

Cystic adventitial disease represents an unusual cause of peripheral vascular insufficiency. A mucinous cyst in the outer media or adventitia progressively compromises the arterial lumen. The therapy can be either aspiration of the cyst or resection with graft interposition. We present two cases involving the popliteal artery that were treated by resection. This lesion may be recognized by its angiographic appearance associated with a lack of generalized atherosclerotic disease.     

Characterization of Lymphocyte Subpopulations and T Cell Activation In Endometriosis

PROBLEM: Numerous studies have characterized the lymphocyte subpopulations in normal eutopic endometrium and suggested a role for the cytokine secretory products of these lymphocytes in regulating endometrial cell proliferation and differentiation. Recent studies have shown that ectopic endometrium contains a greater concentration of scattered stromal lymphocytes than does eutopic endometrium. However, the lymphocyte subpopulations and their activation status have not been characterized in ectopic endometrium. METHODS: We performed immunohistochemical studies on serial sections of proliferative and secretory phase eutopic endometrium and ectopic endometrium obtained during the proliferative phase using monoclonal antibodies to CD4 (T helper-inducer cells), CD8 (T cytolytic-suppressor cells), CD22 (B-cells), CD56 (natural killer cells), and VLA-1 (T-cell activation marker). RESULTS: Ectopic endometrium contained significantly more scattered stromal CD4, CD8, and activated T cells than did proliferative and secretory eutopic endometrium. There were more activated T-cells in proliferative than in secretory eutopic endometrium. Ectopic endometrium contained significantly fewer NK cells than proliferative and secretory endometrium. CONCLUSIONS: These results demonstrate that (1) the increased lymphocyte population in ectopic endometrium is due to increased numbers of CD4 and CD8 cells, and (2) a greater number of activated T cells are present in ectopic endometrium as compared to eutopic endometrium. Increased concentration of stromal T cells and enhanced VLA-1 expression in ectopic endometrium suggest that cytokine products of the activated T-cells may be involved in regulating cellular processes of endometriosis tissue.     

Response of the murine gastrointestinal epithelium to cis-dichlorodiammineplatinum. II: radiation combinations

Single doses of cis-dichlorodiammineplatinum II (cis DDP) up to 8 mg/kg produced a dose-dependent inhibition of proliferative activity with a subsequent period of compensatory hyperplasia in the colon. The stomach was less responsive to cis DDP. Cis DDP-radiation combinations produced a dimunition in the proliferative response of the colon when compared to that following radiation only. This response was only seen in the stomach following 8 mg/kg of cis DDP and radiation. Cytokinetic analysis of the jejunal response to 8 mg/kg of cis DDP showed a gradual reduction in LN and MF/crypt with a reduction in the rate of DNA synthesis of S-phase cells through 8 hours post-treatment. By 24 hours the cellular DNA synthetic rate had recovered, although the number of S-phase cells was further reduced. The previously reported jejunal response to cis DDP-radiation combinations involved a reduction in crypt survival, coupled with a reduced proliferative capacity of surviving cells. Further investigation has revealed a possible inhibition of radiation damage repair by cis DDP, leading to increased levels of cell kill with the combination and reduced recovery of DNA synthetic rates in surviving cells.     

Kinetically directed combination therapy with adriamycin and X-irradiation in a mammary tumor model

In the present studies, the interaction of adriamycin (A) and x-irradiation (X) in T1699 mouse mammary tumors was evaluated. Mitotic indices and thymidine labeling indices were determined at various intervals after A or X alone, and after A + X given in combination. The results with A (1.0 mg/kg) and X (200 R) alone suggests that those quantities of each agent induce a G₂ progression delay of 9–12 brs. The kinetic results after A + X in combination indicated increased S phase transit. time and G₂ progression delay. Recovery kinetics after A + X were used to predict “optimmn” sequence intervals for subsequent A + X fractions. Sequential A + X treatment schedules, up to 4 fractions, were designed and evaluated by regrowth delay measurements. The results indicated that the interaction was additive when A and X were given together in combination. Fractionation of A + X to minimize proliferstive recovery between fractions resulted in an enhanced antitumor effect.