Insulin-like growth factor 1 (IGF1) has been proposed as a ''G 1 -progression factor'' and as a mediator of estradiol's (E2) mitogenic effects on the uterus. To test these hypotheses, we compared E2's mitogenic effects on the uteri of Igf1-targeted gene deletion (null) and wild-type littermate mice. The proportion of uterine cells involved in the cell cycle and G 1 -and S-phase kinetics were not significantly different in wild-type and Igf1-null mice. However, the appearance of E2-induced mitotic figures and cell number increases were profoundly retarded in Igf1-null uterine tissue. There was a significant increase in nuclear DNA concentration in Igf1-null cells, consistent with a G 2 arrest. Interestingly, apoptotic cells were also significantly reduced in abundance, and the normal massive apoptotic response to E2 withdrawal was absent in the Igf1-null uterus. These data show that Igf1 is an essential mediator of E2's mitogenic effects, with a critical role not in G 1 progression but in G 2 progression.Estradiol (E2) has potent stimulatory effects on uterine growth, with unopposed E2 action culminating in uterine neoplasia. Media from E2-treated uterine explants contains factors capable of stimulating tumor cell proliferation, suggesting that E2's mitogenic effects are mediated by local growth factor production (1). Insulin-like growth factor 1 (IGF1) has been implicated as a potential mediator of E2's effects on uterine growth [''estromedin'' (2)] because E2 induces uterine IGF1 expression (3-11) in a pattern that shows a significant spatiotemporal correlation with E2-induced cell proliferation (11). Furthermore, Igf1-targeted gene deletion mice demonstrate a disproportionate reduction in uterine size, although it is not clear whether this is caused by reduced estrogen production (12) or by impaired estrogen effect on the uterus secondary to absent local IGF1. To test the hypothesis that IGF1is required for E2-induced mitogenesis and to identify the cell-cycle stages in which IGF1 acts in vivo, we compared the effects of exogenous E2 treatment on uterine cell-cycle parameters in homozygous Igf1 null and wild-type (wt) littermate mice.
In conclusion, GTP supplementation mitigated deterioration of bone microarchitecture and improved bone integrity in rats with chronic inflammation by suppressing bone erosion and modulating cancellous and endocortical bone compartments, resulting in a larger net bone volume. Such a protective role of GTP may be due to a suppression of TNF-α.
h Paraconiothyrium cyclothyrioides is a recently described coelomycetous fungal species. We present a case in a renal transplant patient with chronic skin lesions of the lower extremities caused by P. cyclothyrioides. Treatment with posaconazole led to complete resolution of the lesions. P. cyclothyrioides should be considered an opportunistic human pathogen in immunocompromised patients. CASE REPORTA 49-year-old Latin American man with end-stage renal disease and a cadaveric renal transplant (2 years prior to the current admission) was hospitalized with cutaneous lesions in his lower extremities. The patient had history of type II diabetes, hypertension, and atrial fibrillation. One and half years previous to admission, the patient received thymoglobulin for acute T-cell rejection, with improvement of the episode. Approximately 6 months before the current admission, the patient first noticed a painless, nonpruritic, mildly tender scaly papule on the left tibia just inferior to the knee joint and applied a local adhesive band to prevent friction injury. Over the next few months, other lesions appeared on both tibial surfaces which then began to coalesce into violaceous, necrotic, plaque-like lesions with some areas of ulceration and crusting and mild self-limiting sanguineous discharge without accompanying fevers. The patient lives in Brownsville, TX, works in an office as a manager, and denied any travel outside Texas, trauma, or animal or insect bites. The patient's hobbies include performing mechanical work on car engines. Medications included leflunomide, prednisone, tacrolimus, doxazosin, clonidine, carvedilol, minoxidil, amlodipine, trimethoprim-sulfamethoxazole, insulin, famotidine, gemfibrozil, and pravastatin. His complete blood count was notable for a platelet count of 73 and creatinine of 2.4 mg/dl. On physical examination, he was afebrile and vital signs were stable. A cardiac examination evidenced an irregular rate and a II/VI murmur loudest in the apex. The lungs were clear, and the rest of the examination was unremarkable except for the lower extremities. He had a crusted, ulcerated plaque on the anteromedial aspect of the left knee (measuring 6 by 3 cm) and several similar-appearing lesions of smaller size on the same area (Fig. 1A). The patient was started on vancomycin (1.25 g every 24 h); radiographs of the knee did not reveal any bone abnormality. A skin biopsy specimen yielded a presumptive diagnosis of pyoderma gangrenosum, antibiotics were stopped, and the patient was discharged with wound care instructions and silver sulfadiazine.Two months prior to the current admission, a fungal culture from the skin tissue was positive for a single mold which grew on Sabouraud dextrose (Sab Dex) agar but was not identified at the time. Oral voriconazole (200 mg orally every 12 h) administration was initiated. A month after his discharge, he presented to the dermatology clinic with evidence of progression of his skin lesions and was again admitted to the hospital. He denied new recent trauma or travel h...
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