Ectopic Leydig cells of testis An immunohistochemical study on tissue microarray.

The incidence of ectopic Leydig cells (LCs) has been reported to be 40% to 90%. Several theories have been proposed to account for ectopic LCs, including in situ differentiation, migration from testicular interstitium, and trapping of peritubular LCs in the tunica propria of the seminiferous tubule during its thickening. To document the nature of ectopic LCs and to compare them with interstitial LCs, Sertoli cells, epididymal cells, mesothelial cells, and epithelial cells in rete testis, immunostainings with calretinin, CD10, inhibin, CK7, and CK20 were performed in 40 cases of orchiectomy specimens using tissue microarray sections. In addition, the frequency of ectopic LCs was evaluated. Of the 40 orchiectomy specimens, 14 cases demonstrated ectopic LCs with an incidence of 35%. Inhibin was positive in more than half of ectopic LCs (9/14, 64.3%) and in almost all interstitial LCs. Calretinin was positive in most of ectopic LCs (12/14, 85.7%) as well as in most of normally located interstitial LCs and mesothelial cells and some of rete testis epithelial cells. The ectopic and interstitial LCs as well as Sertoli cells were negative for CK7, CK20, and CD10. CK7 was positive in all epididymal cells and in most mesothelial cells and epithelial cells in rete testis. CD10 was positive in some of epididymal cells and epithelial cells in rete testis. CK20 was negative in all cells in the testis and epididymis. Ectopic LCs showed similar staining patterns to interstitial LCs with positive immunoreactivity for calretinin and inhibin. In this study, the frequency of ectopic LCs was 35%. The lower incidence in this study was most likely because of the limited sampling. Immunohistochemically, ectopic LCs showed identical immunohistochemical patterns with those of interstitial LCs. Calretinin appeared to be more sensitive but less specific than inhibin for LCs. Because calretinin is frequently positive in cells other than ectopic or interstitial LCs, a precaution is required to differentiate LCs from mesothelial cells and rete testis epithelial cells. Based on our study, we could not add anything else of what is known in regard to the histogenesis of ectopic LCs. The current theories including in situ differentiation, migration from testicular interstitium, and trapping of peritubular LCs in the tunica propria of the seminiferous tubules during its thickening seem to be valid histogenetic theories.

Fractalkine mediates T cell-dependent proliferation of synovial fibroblasts in rheumatoid arthritis.

OBJECTIVE: In rheumatoid arthritis (RA), synovial fibroblasts proliferate excessively, eventually eroding bone and cartilage. The aim of this study was to examine the mechanisms through which CD4 T cells, the dominant lymphocyte population in patients with rheumatoid synovitis, regulate synoviocyte proliferation. METHODS: Fibroblast-like synoviocyte (FLS) lines were established from rheumatoid synovium. CD4 T cells from patients with RA and age-matched control subjects were cultured on FLS monolayers. FLS proliferation was quantified by cytometry, using carboxyfluorescein succinimidyl ester staining or microscopic enumeration of PKH26-stained FLS. Surface expression of the fractalkine (FKN) receptor CX(3)CR1 was monitored by fluorescence-activated cell sorting. The induction of CX(3)CR1 and its ligand FKN in FLS was quantified by real-time polymerase chain reaction. RESULTS: The proliferation of FLS was significantly increased in the presence of CD4 T cells from patients with RA compared with control T cells. CD4+,CD28- T cells were particularly effective in supporting FLS growth, inducing a 25-fold expansion compared with a 5-fold expansion induced by CD4+,CD28+ T cells. The growth-promoting activity of CD4+,CD28- T cells was mediated through CX(3)CR1, a chemokine receptor expressed on both T cells and FLS. Anti-CX(3)CR1 antibodies inhibited T cell production of tumor necrosis factor alpha (TNFalpha) and suppressed FLS proliferation. TNFalpha amplified the expansion of FLS by enhancing their expression of CX(3)CR1 and FKN. CONCLUSION: FKN-CX(3)CR1 receptor-ligand interactions regulate FLS growth and FLS-dependent T cell function. FLS stimulate autocrine growth by releasing FKN and triggering the activity of their own CX(3)CR1. This growth-promotion loop is amplified by TNFalpha produced by CX(3)CR1-expressing T cells upon stimulation by FKN-expressing FLS. These data assign a critical role to FKN and its receptor in fibroblast proliferation and pannus formation in RA.

Fetal growth and neonatal mortality in Korea.

The fetal growth curve and neonatal mortality rate, based on gestational age and birthweight, are important for identifying groups of high-risk neonates and developing appropriate medical services and health-care programmes. The purpose of this study was to develop a national fetal growth curve for neonates in Korea, and examine the Korean national references for fetal growth and death according to their characteristics. Data of Korean vital statistics linked National Infant Mortality Survey conducted on births in 1999 were used in this study. The total livebirths were 621,764 in 1999, which were grouped into singletons (n = 609,643) and twins (n = 9805) for analysis. Birthweight/gestational age-specific fetal growth curves and neonatal mortality rates were based on 250 g of birthweight and weekly gestational age intervals for each characteristic of the birth. The features of high-risk neonates such as small-for-gestational-age and the limit of viability in Korea were different from those of Western countries. Difference in fetal growth and death was also detected in other characteristics of the fetus (gender and plurality of birth) besides race. The fetal growth curve of males was higher than that of females, and was higher in singleton than in twins. The neonatal mortality rate was higher in males (singleton, 2.6; twin, 23.5) than females (singleton, 2.1; twin, 15.9), and higher in twins (19.8/1000) than in singletons (2.4/1000). However, in neonates with gestational age >29 weeks and birthweight >1000 g, the neonatal mortality rate was lower in twins than in singletons. The limit of viability was gestational age 27 weeks and birthweight 1000 g, which was similar in singletons and twins regardless of gender. To improve the health of neonates in a country, it is imperative to investigate the characteristics of fetal growth and death under the particular circumstances of the country. When risk is defined for neonates account must be taken of differences in race, gender and plurality of birth, as the neonatal mortality rate varies depending on those factors.

BLyS and APRIL in rheumatoid arthritis.

The cytokines B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) enhance autoimmune disease by sustaining B cell activation. In RA, B cells contribute to the formation of 3 functionally distinct types of lymphoid microarchitectures in the inflamed synovium: ectopic GCs; T cell-B cell aggregates lacking GC reactions; and unorganized, diffuse infiltrates. We examined 72 tissues representing the 3 types of synovitis for BLyS and APRIL production and for expression of APRIL/BLyS receptors. Biologic effects of BLyS and APRIL were explored by treating human synovium-SCID mouse chimeras with the APRIL and BLyS decoy receptor transmembrane activator and CAML interactor:Fc (TACI:Fc). GC+ synovitis had the highest levels of APRIL, produced exclusively by CD83+ DCs. BLyS was present in similar levels in all tissue types and derived exclusively from CD68+ macrophages. In GC+ synovitis, treatment with TACI:Fc resulted in GC destruction and marked inhibition of IFN-gamma and Ig transcription. In contrast, inhibition of APRIL and BLyS in aggregate and diffuse synovitis left Ig levels unaffected and enhanced IFN-gamma production. These differential immunomodulatory effects correlated with the presence of TACI+ T cells in aggregate and diffuse synovitis and their absence in GC+ synovitis. We propose that BLyS and APRIL regulate B cell as well as T cell function and have pro- and antiinflammatory activities in RA.