Background: The prevalence and clinical characteristics of osteochondritis dissecans (OCD) of the humeral capitellum among adolescent baseball players are unknown. Purpose: To determine the OCD prevalence in adolescent competitive baseball players and to investigate the clinical characteristics of these patients. Study Design: Cross-sectional and case-control study; Level of evidence, 3. Methods: A total of 2433 baseball players (mean age, 14.5 ± 1.5 years) belonging to junior high school and high school baseball clubs were enrolled. Players completed a questionnaire, and the elbow of each player’s throwing arm was assessed by ultrasonography. Participants with abnormal results on ultrasonography were further examined through radiographic study. The OCD lesions were classified into stages based on radiographic results, and demographic data were compared between players with and without OCD lesions. Results: Osteochondritis dissecans of the humeral capitellum was found in 82 (3.4%) elbows by ultrasonography. Players with an OCD lesion began playing baseball at an earlier age ( P = .016), had a longer duration of competitive play ( P = .0013), and had experienced more present ( P = .0025) and past ( P < .0001) elbow pain compared with players without a lesion. There were no differences between the 2 groups in the position played ( P = .26). Sixty-eight patients underwent further radiographic examination for OCD (radiography, computed tomography, magnetic resonance imaging). Of these players, 10 (14.7%) were classified as having stage I OCD (radiolucent stage); 26 (38.2%), stage II (fragmentation stage); 9 (13.2%), stage III (loose body stage); 9 (13.2%), stage IV (residual stage); and 14 (23.5%), stage V (postoperative stage). Conclusion: The prevalence of OCD of the humeral capitellum, including latent cases, was 3.4% among adolescent baseball players. Players with OCD lesions began playing baseball at earlier ages, had played for longer periods, and had experienced more elbow pain. The player’s current baseball position may not be related to the existence of OCD lesions in adolescents.

BACKGROUND: There are few effective approaches to infertile patients with repeated failure in IVF–embryo transfer therapy. Since recent evidence suggests that some populations of maternal immune cells positively support embryo implantation, we have developed a new approach using peripheral blood mononuclear cells (PBMCs). METHODS: Patients who had not experienced successful pregnancy despite four or more IVF–embryo transfer sessions were enrolled in this study (n = 35, 35 cycles). PBMCs were obtained from patients on the day of oocyte retrieval and were cultured with HCG for 48 h. Two days later, PBMCs were freshly isolated from patients again, combined with cultured PBMC and then administered to the intrauterine cavity of the patients. Blastocyst transfer was performed on day 5, and the success of implantation in the PBMC-treated group was compared with that in the non-treated group. RESULTS: Clinical pregnancy rate, implantation rate and live birth rate in the PBMC-treated group (41.2, 23.4 and 35.3%; n = 17, 47 and 16, respectively) were significantly higher than those in the non-treated group (11.1, 4.1 and 5.5%; n = 18, 49 and 18, respectively). CONCLUSION: Intrauterine administration of autologous PBMC may be an effective approach to improve embryo implantation in patients with repeated IVF failures.

At the human feto-maternal interface, trophoblasts differentiate towards extravillous trophoblasts (EVTs) and form the cell column. EVTs acquire invasive activity in the distal part of the cell column and begin to migrate into the maternal tissue. We previously reported that dipeptidyl peptidase IV (DPPIV) is expressed on EVTs in the proximal part of cell column and is involved in the inhibition of their migration. Because DPPIV has been shown to degrade several chemokines, we examined possible roles of chemokines in EVT migration. Immunohistochemistry demonstrated that C-C chemokine receptor 1 (CCR1) was hardly detected on cytotrophoblasts and syncytiotrophoblast but was expressed on EVTs in the cell column. In vitro, CCR1 protein was also present on the surface of EVTs that grew out from chorionic villous explants cultured under 20% O₂. Chemokines that can bind to CCR1 (CCR1 ligands), such as regulated on activation, normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein-1α (MIP-1α), were confirmed in the decidual tissues by RT-PCR and immunohistochemistry. These CCR1 ligands promoted the migration of the EVTs that were isolated from the explant cultures in vitro. These results indicate that CCR1 is expressed on trophoblasts as they differentiate to EVTs and that CCR1 ligands produced from the decidual tissue induce EVT migration. By contrast, CCR1 was scarcely expressed on EVTs that grew out from villous explants cultured in 1% O₂, indicating that a relatively high oxygenic environment is needed to induce CCR1 expression. Moreover, CCR1 expression on the isolated EVTs was significantly reduced in the presence of decidua-conditioned medium. Such regulation of CCR1 by surrounding oxygenic and decidual environments supports a close correlation between EVT invasion and their expression of CCR1. This study demonstrates that trophoblasts acquire CCR1 as they differentiate to an invasive phenotype at the villus-anchoring sites and indicates a novel role for the chemokine-CCR1 system in the initial step of trophoblastic invasion towards the maternal tissue.

In order to elucidate the role of androgen receptors (AR) in human ovaries, we examined their immunohistochemical localization, in comparison with oestrogen receptors (ER) and progesterone receptors (PR), at various stages of the menstrual cycle and follicular development. Primordial and primary follicles did not express AR. In granulosa and thecal cells of secondary follicles there was weak nuclear staining for AR. Granulosa cells of dominant follicles showed moderate nuclear staining for AR, which was stronger than that in thecal cells. In the luteal phase, the staining intensity for AR was strongest in the early luteal phase just after ovulation and declined gradually thereafter. Thecal cells of atretic follicles showed moderate nuclear staining for AR, which was a little stronger than that in dominant follicles. There was weak nuclear staining for AR in stromal cells surrounding follicles. Though there was variation in the staining intensity, AR were present at almost all stages of the menstrual cycle. There is a possibility that androgens, mediated by AR, may play an essential role in follicular growth and maturation, atresia and luteinization as autocrine or paracrine agents.

Human luteal cells have been reported to express human leukocyte antigen-DR and lymphocyte functional antigen-3 on the cell surface, suggesting physiological interaction between luteal cells and T-lymphocytes through the menstrual cycle into early pregnancy. To elucidate the role of peripheral lymphocytes on corpus luteum differentiation, the effect of peripheral blood mononuclear cells (PBMC) on steroidogenesis by luteal cells was investigated. The production of Th-2 cytokines such as interleukin (IL)-4 and IL-10 by the co-cultured cells was also examined, and the effects of these cytokines on progesterone production by luteal cells were investigated. Corpora lutea were obtained from eight non-pregnant women in the luteal phase and five women in early pregnancy for luteal cell culture. PBMC were isolated from unrelated women in the follicular phase, secretory phase, and early pregnancy. After coculture with allogenic PBMC for 48 h, progesterone production was significantly enhanced by PBMC from the secretory phase and early pregnancy in the non-pregnant luteal cell culture. In the pregnant luteal cell culture, a significant increase in progesterone production was also observed by the co-culture with PBMC from women in early pregnancy, showing that PBMC have a luteotrophic effect. The stimulatory effects of PBMC were also observed in co-culture conditions which prevented direct cell-to-cell interaction with luteal cells, showing the minor influence of mixed lymphocyte reaction. By co-culture with PBMC, the production of IL-10, but not IL-4, was significantly augmented in luteal cell culture derived from non-pregnant women, whereas the production of both IL-4 and IL-10 was significantly enhanced in the luteal cell culture derived from pregnant women. Moreover, IL-4 and IL-10 promoted progesterone production by cultured luteal cells, especially in the luteal cell culture derived from corpora lutea of early pregnancy. These findings indicate that PBMC stimulate progesterone production by luteal cells and suggest the involvement of PBMC in corpus luteum function and differentiation probably via the Th-2-type lymphocytes.

Dysfunction of p53 is observed in the many malignant tumors. In cervical cancer, p53 is inactivated by degradation through the complex with human papilloma virus (HPV) oncoprotein E6 and E6-associated protein (E6AP), an E3 ubiquitin protein ligase. In endometrial cancer, overexpression of p53 in immunohistochemistry is a significant prognostic factor. A discrepancy between p53 overexpression and TP53 mutations is observed in endometrioid endometrial cancer, indicating that the accumulation of p53 protein can be explained by not only gene mutations but also dysregulation of the factors such as ERβ and MDM2. Furthermore, the double-positive expression of immunoreactive estrogen receptor (ER) β and p53 proteins is closely associated with the incidence of metastasis and/or recurrence. High-grade serous ovarian carcinoma (HGSC) arises from secretary cells in the fallopian tube. The secretary cell outgrowth (SCOUT) with TP53 mutations progresses to HGSC via the p53 signature, serous intraepithelial lesion (STIL), and serous intraepithelial carcinoma (STIC), indicating that TP53 mutation is associated with carcinogenesis of HGSC. Clinical application targeting p53 has been approved for some malignant tumors. Gene therapy by the adenovirus-mediated p53 gene transfer system is performed for head and neck cancer. A clinical phase III trial using MDM2/X inhibitors, idasanutlin (RG7388) combined with cytarabine, is being performed involving relapse/refractory acute myeloid leukemia patients. The use of adenoviruses as live vectors which encode wild-type p53 has given promising results in cervical cancer patients.