Capsular synovial metaplasia as a common response to both textured and smooth implants

Recent reports suggested that the presence of synovial metaplasia in the capsular tissues of breast implants is greater with textured-shelled implants compared with smooth. Textured implants, however, have become popular only in the last few years. Therefore, the studies do not address the possibility that synovial metaplasia may be a dynamic process related to time (e.g., implant age) rather than implant shell surface. In the current study, 159 implant capsules (85 patients) removed between February of 1992 and July of 1993 at UCLA Medical Center were evaluated histologically and correlated with clinical data, including the age of implants. Synovial metaplasia was identified in 40 percent (64 of 159) of the capsule specimens. A logistic regression analysis that removed the effect of implant age demonstrated no correlation of implant shell type (textured versus smooth) with the presence of synovial metaplasia. Gel bleed, implant location, pericapsular fluid, implant rupture, and capsular contracture also did not have any significant association with synovial metaplasia in the current study. The incidence of synovial metaplasia appears to decrease with age (77 percent at < 5 years; 22 percent at > 15 years). Our findings suggest that synovial metaplasia is not rare and in fact may be a fairly common transitional histologic finding. It may be part of the common progression that occurs at the implant-capsule interface. The clinical significance remains unknown.     

Adeno-associated viral-mediated catalase expression suppresses optic neuritis in experimental allergic encephalomyelitis

Suppression of oxidative injury by viral-mediated transfer of the human catalase gene was tested in the optic nerves of animals with experimental allergic encephalomyelitis (EAE). EAE is an inflammatory autoimmune disorder of primary central nervous system demyelination that has been frequently used as an animal model for the human disease multiple sclerosis (MS). The optic nerve is a frequent site of involvement common to both EAE and MS. Recombinant adeno-associated virus containing the human gene for catalase was injected over the right optic nerve heads of SJL/J mice that were simultaneously sensitized for EAE. After 1 month, cell-specific catalase activity, evaluated by quantitation of catalase immunogold, was increased approximately 2-fold each in endothelia, oligodendroglia, astrocytes, and axons of the optic nerve. Effects of catalase on the histologic lesions of EAE were measured by computerized analysis of the myelin sheath area (for demyelination), optic disc area (for optic nerve head swelling), extent of the cellular infiltrate, extravasated serum albumin labeled by immunogold (for blood-brain barrier disruption), and in vivo H2O2 reaction product. Relative to control, contralateral optic nerves injected with the recombinant virus without a therapeutic gene, catalase gene inoculation reduced demyelination by 38%, optic nerve head swelling by 29%, cellular infiltration by 34%, disruption of the blood-brain barrier by 64%, and in vivo levels of H2O2 by 61%. Because the efficacy of potential treatments for MS are usually initially tested in the EAE animal model, this study suggests that catalase gene delivery by using viral vectors may be a therapeutic strategy for suppression of MS.     

Direct measurement of the energy expenditure of physical activity in preterm infants

The energy cost of physical activity (EEA) has been estimated to account for 5-17% of total energy expenditure (TEE) in neonates. To directly measure EEA, a force plate was developed and validated to measure work outputs ranging from 0.3 to 40 kcal . kg-1 . day-1. By use of this force plate plus indirect calorimetry, TEE and EEA were measured and correlated with five activity states in 24 infants with gestational age of 31.6 +/- 0.5 (SE) wk and postnatal age of 24.8 +/- 3.7 days. TEE and EEA were 69.2 +/- 1.5 and 2.4 +/- 0.2 kcal . kg-1 . day-1, respectively. EEA per state was 0.5 +/- 0.0 (quiet sleep), 2.4 +/- 0.2 (active sleep), 2.8 +/- 0.4 (quiet awake), 7.5 +/- 0.8 (active awake), and 15.1 +/- 2.3 (crying) kcal . kg-1 . day-1. This provides the first direct measurement of the contribution of physical activity to TEE in preterm infants and will enable measurement of caloric expenditure from muscle activity in various disease conditions and development of nursing strategies to minimize unnecessary energy losses.     

Involvement of IL-16 in the induction of airway hyper-responsiveness and up-regulation of IgE in a murine model of allergic asthma

Experiments were designed to investigate the role of IL-16 in a mouse model of allergic asthma. OVA-sensitized mice were repeatedly exposed to OVA or saline aerosols. Bronchoalveolar lavage fluid (BALF) was collected after the last aerosol, and the presence of IL-16 was evaluated using a migration assay with human lymphocytes. Migration of lymphocytes was significantly increased in the presence of cell-free BALF from OVA-challenged mice compared with BALF from saline-challenged controls. This response was significantly inhibited after addition of antibodies to IL-16, demonstrating the presence of IL-16 in BALF of OVA-challenged animals. Immunohistochemistry was performed and revealed IL-16 immunoreactivity particularly in airway epithelial cells but also in cellular infiltrates in OVA-challenged mice. IL-16 immunoreactivity was absent in nonsensitized animals; however, some reactivity was detected in epithelial cells of sensitized but saline-challenged mice, suggesting that sensitization induced IL-16 expression in airway epithelium. Treatment of mice with antibodies to IL-16 during the challenge period significantly suppressed up-regulation of OVA-specific IgE in OVA-challenged animals. Furthermore, antibodies to IL-16 significantly inhibited the development of airway hyper-responsiveness after repeated OVA inhalations, whereas the number of eosinophils in bronchoalveolar lavage or airway tissue was not affected. In conclusion, IL-16 immunoreactivity is present in the airways after sensitization. After repeated OVA inhalation, IL-16 immunoreactivity is markedly increased and IL-16 is detectable in BALF. Furthermore, IL-16 plays an important role in airway hyper-responsiveness and up-regulation of IgE but is not important for eosinophil accumulation in a mouse model of allergic asthma.     

Regulation of rat pituitary gonadotropin-releasing hormone receptor mRNA levels in vivo and in vitro

The recent isolation of cDNAs encoding the rat pituitary gonadotropin-releasing hormone receptor (GnRHR) allows studies of the regulation of the synthesis of the GnRHR and its relationship to reproductive function. Analyses of the regulation of GnRHR mRNA levels in the rat pituitary in vivo revealed a progressive increase in levels to 2.0 +/- 0.2-fold after ovariectomy (OVX) and 5.2 +/- 1.3-fold after castration (CAST) (21 days post-operative), compared to intact adult female and male controls, respectively. Replacement therapy with 17 beta-estradiol benzoate in 21-day post-OVX female rats resulted in a marked decrease in GnRHR mRNA levels by 7 days, compared to controls. In contrast, therapy with testosterone propionate in 21-day post-CAST male rats resulted in only a modest decrease in GnRHR mRNA levels. Thus, manipulation of the reproductive endocrine system in vivo results in alterations in GnRHR synthesis at the pretranslational level, which parallel known changes in cell surface gonadotropin-releasing hormone (GnRH) binding activities. The treatment of superfused primary monolayer cultures of rat pituitary cells with hourly pulses of GnRH (10 nM, 6 min/h) resulted in a marked increase in GnRHR mRNA levels (12.8 +/- 4.3-fold compared to untreated cells). In contrast, treatment of cultured cells with continuous GnRH caused no change in GnRHR mRNA levels. These in vitro data show homologous regulation of GnRHR gene expression by GnRH, and suggest that the changes in GnRHR gene expression observed in vivo may be attributable at least in part to changes in the pattern of hypothalamic GnRH secretion.     

Secondary 18O and primary 13C isotope effects as a probe of transition-state structure for enzymatic decarboxylation of oxalacetate

A new method for directly measuring 18O isotope effects on decarboxylation reactions has been developed. By running the reaction under high vacuum (10(-5) torr), CO2 leaves the solution before exchange with the oxygens of water to an extent greater than 2%. Thus, the method permits determination of 18O isotope effects with the precision of the isotope ratio mass spectrometer, and without the necessity of resorting to the remote label method and its attendant required syntheses. The method is used to determine 18O isotope effects for decarboxylation of oxalacetate (OAA) by Mg2+, and enzymatically by OAA decarboxylase from Pseudomonas putida; 13C isotope effects are also reported for this enzyme, as well as for decarboxylation of OAA by pyruvate kinase. Initial velocity patterns and pH profiles are reported for the P. putida enzyme, and all available data are used to discuss the kinetic and chemical mechanism of decarboxylation.     

Effect of reperfusion on biventricular function and survival after right ventricular infarction

BACKGROUND: Although the salutary effects of reperfusion in patients with left ventricular infarction are well documented, the benefits in patients with acute right ventricular infarction are less clear. METHODS: To determine whether primary angioplasty improves right ventricular function and the clinical outcome in patients with right ventricular infarction, we performed echocardiographic studies before and after angioplasty in 53 patients with acute right ventricular infarction. RESULTS: Complete reperfusion, defined as normal flow in the right main coronary artery and its major right ventricular branches, was achieved in 41 patients (77 percent), leading to prompt and striking recovery of right ventricular function (mean [+/-SE] score for free-wall motion, 3.0+/-0.1 at base line and 1.4+/-0.1 at three days; P<0.001). Twelve patients (23 percent) had unsuccessful reperfusion, defined as the failure to restore right ventricular branch flow, with or without patency of the right main coronary artery. Unsuccessful reperfusion was associated with lack of recovery of right ventricular function (score for free-wall motion, 3.2+/-0.2 at base line and 3.0+/-0.9 at three days; P= 0.55), as well as persistent hypotension and low cardiac output (in 83 percent of the patients, vs. 12 percent of those with successful reperfusion; P=0.002) and a high mortality rate (58 percent, vs. 2 percent for those with successful reperfusion; P=0.001). CONCLUSIONS: In patients with right ventricular infarction, complete reperfusion of the right coronary artery by angioplasty results in the dramatic recovery of right ventricular performance and an excellent clinical outcome. In contrast, unsuccessful reperfusion is associated with impaired recovery of right ventricular function, persistent hemodynamic compromise, and a high mortality rate.