Broadband, unpolarized repumping and clearout light sources for Sr(+) single-ion clocks.

Future transportable optical clocks require compact and reliable light sources. Here, broadband, unpolarized repumper and state clearout sources for Sr+ single-ion optical clocks are reported. These turn-key devices require no frequency stabilization or external modulators. They are fiber based, inexpensive, and compact. Key characteristics for clock operation are presented, including optical spectra, induced light shifts, and required extinction ratios. Tests with an operating single-ion standard show a clearout efficiency of 100%. Compared to a laser-based repumper, the achievable fluorescence rates for ion detection are a few tens of percent lower. The resulting ion kinetic temperature is 1-1.5 mK, near the Doppler limit of the ion system. Similar repumper light sources could be made for Ca+ (866 nm) and Ba+ (650 nm) using semiconductor gain media.

Guidelines on the use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal surface malignancy arising from colorectal or appendiceal neoplasms.

To meet the needs of patients, Canadian surgical and medical oncology leaders in the treatment of peritoneal surface malignancies (psms), together with patient representatives, formed the Canadian HIPEC Collaborative Group (chicg). The group is dedicated to standardizing and improving the treatment of psm in Canada so that access to treatment and, ultimately, the prognosis of Canadian patients with psm are improved. Patients with resectable psm arising from colorectal or appendiceal neoplasms should be reviewed by a multidisciplinary team including surgeons and medical oncologists with experience in treating patients with psm. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy should be offered to appropriately selected patients and performed at experienced centres. The aim of this publication is to present guidelines that we recommend be applied across the country for the treatment of psm.

Nonsyndromic tooth agenesis patterns and associated developmental dental anomalies: a literature review with radiographic illustrations.

Tooth agenesis is one of the most intriguing phenomena, because it is frequently associated with other oral anomalies, structural variations and malformations of other teeth, late eruption, transposition and crowding. The diagnosis can be quite challenging as radiographic examination is critical for the diagnosis but not always possible and the late developing teeth may be sometimes scored developmentally missing. Accurate diagnosis therefore requires radiographic, clinical, and dental cast examinations. It is an important clinical and public health problem. Patients with missing permanent teeth may suffer from a reduced chewing ability, inarticulate pronunciation, and an unfavorable aesthetic appearance. Clinically, early diagnosis of a dental anomaly can alert the clinician to the possible development of other associated dental anomalies in the same patient or family, and avoid the possible sequelae. Understanding of tooth agenesis patterns and their impact on diagnosis, prevention, and eventually therapeutics are becoming integral parts of comprehensive dental care. Dental examination with radiographic screening of hypodontia in early childhood should be emphasized as part of public oral health policy to allow early diagnosis and timely intervention.

Regulation of contact hypersensitivity by interleukin 10.

Contact hypersensitivity (CHS) responses require the participation of T cells, along with a variety of cytokines and adhesion molecules. In the classical CHS, antigen-specific T cells are recruited to a site of antigenic challenge, where they react with antigen, release cytokines, and attract other inflammatory cells. In the mouse model of CHS, this reaction is elicited in sensitized mice by application of the immunogen 4-7 d after immunization. The reaction peaks at 24 h, is slightly reduced by 48 h, and can return to normal by 72 h. This is in spite of the fact that some antigen is still present at the site of challenge. Here we examined the hypothesis that locally produced interleukin 10 (IL-10) regulates the duration of the response. Our data show that IL-10 protein peaked 10-14 h after antigenic challenge and returned to background by 24 h. The production of IL-10 protein corresponded with, and followed IL-10 mRNA transcription as detected by reverse transcriptase-polymerase chain reaction. During peak IL-10 production after antigenic challenge, it was not possible to transfer CHS with immune lymphoid cells, unless neutralizing antibody to IL-10 was given first. Additionally, when sensitized mice were given neutralizing anti-IL-10 antibody at the time of antigenic challenge, the duration of CHS was prolonged well beyond the natural course of the response. Finally, we demonstrate that rIL-10, when injected into the skin before antigenic challenge, prevented the elicitation of CHS in previously sensitized mice. Taken together, our data show an important role for IL-10 in the natural regulation of CHS responses in vivo.

Tumour response 3 months after neoadjuvant single-fraction radiotherapy for low-risk breast cancer.

Introduction: Standard treatment for early-stage invasive breast cancer (bca) consists of breast-conserving surgery and several weeks of adjuvant radiotherapy (rt). Neoadjuvant single-fraction rt is a novel approach for early-stage bca. We sought to investigate the effect of delaying surgery after neoadjuvant rt with respect to the rate of pathologic response (pr). Methods: Women 65 years of age or older with a new diagnosis of stage i luminal A bca were eligible for inclusion. A single 20 Gy dose to the primary breast tumour was given, followed by breast-conserving surgery 3 months later. The primary endpoint was the pr rate assessed by microscopic evaluation using the Miller-Payne system. Results: To date, 10 patients have been successfully treated. Median age of the patients was 72 years (range: 65-84 years). In 8 patients, neoadjuvant rt resulted in a tumour pr with median residual cellularity of 3%. No immediate rt complications other than mild dermatitis were noted. Conclusions: This study demonstrates a method for delivering single-fraction rt that can lead to a high level of pr in most patients. Continued accrual to this study and subsequent trials are needed to determine the feasibility, safety, and role of this novel technique in the management of early-stage bca.

Canadian guidelines on the management of colorectal peritoneal metastases.

Modern management of colorectal cancer (crc) with peritoneal metastasis (pm) is based on a combination of cytoreductive surgery (crs), systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy (hipec). Although the role of hipec has recently been questioned with respect to results from the prodige 7 trial, the role and benefit of a complete crs were confirmed, as observed with a 41-month gain in median survival in that study, and 15% of patients remaining disease-free at 5 years. Still, crc with pm is associated with a poor prognosis, and good patient selection is essential. Many questions about the optimal management approach for such patients remain, but all patients with pm from crc should be referred to, or discussed with, a pm surgical oncologist, because cure is possible. The objective of the present guideline is to offer a practical approach to the management of pm from crc and to reflect on the new practice standards set by recent publications on the topic.

Rationale for the administration of systemic 5-FU in combination with heated intraperitonal oxaliplatin.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin (OX) is the standard of care for selected patients with peritoneal carcinomatosis of colorectal origin. Because 5-FU is mandatory to improve efficacy of OX when used by systemic route, several teams now empirically combine intravenous (IV) 5-FU with HIPEC OX, but this practice has yet to be supported by preclinical data. Using a murine model, we studied the impact of IV 5-FU on peritoneal absorption of HIPEC OX. METHODS: Under general anesthesia, 24 Sprague-Dawley rats were submitted to 4 different doses of IV 5-FU (0, 100, 400 and 800 mg/m2) and a fixed dose of HIPEC OX (460 mg/m2) perfused at 40 °C during 25 min. At 25 min, samples in different compartments were harvested (peritoneum, portal vein and systemic blood) and the concentrations of 5-FU and OX were measured by high performance liquid chromatography. RESULTS: Peritoneal absorption of OX was significantly higher (17.0, 20.1, 34.9 and 38.1 nmol/g, p < 0.0001) with increasing doses of 5-FU (0, 100, 400 and 800 mg/m2, respectively). Peritoneal absorption of OX reached a plateau between 400 and 800 mg/m2 of IV 5-FU. CONCLUSION: IV 5-FU enhances peritoneal absorption of HIPEC OX. The most efficient dose of IV 5-FU to be used in combination with HIPEC OX seems to be 400 mg/m2.

The current practice of cytoreductive surgery and HIPEC for colorectal peritoneal metastases: Results of a worldwide web-based survey of the Peritoneal Surface Oncology Group International (PSOGI).

BACKGROUND: At present, selected patients with resectable colorectal peritoneal metastases (CRC-PM) are increasingly treated with a combination therapy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to investigate the current worldwide practice. METHODS: HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning their personal expertise and current hospital and countrywide practice. RESULTS: It is estimated that currently more than 3800 patients with CRC-PM (synchronous and metachronous) are annually treated with CRS and HIPEC in 430 centers. Integration of CRS and HIPEC in national guidelines varies, resulting in large treatment disparities between countries. Amongst the experts, there was general agreement on issues related to indication, surgical technique and follow up but less on systemic chemotherapy or proactive strategies. CONCLUSION: This international survey demonstrates that CRS and HIPEC is now performed on a large scale for CRC-PM patients. Variation in treatment may result in heterogeneity in surgical and oncological outcomes, emphasising the necessity to reach consensus on several issues of this comprehensive procedure. Future initiatives directed at achieving an international consensus statement are needed.

Identification of a polar region in transmembrane domain 6 that regulates the function of the G protein-coupled alpha-factor receptor.

The alpha-factor pheromone receptor (Ste2p) of the yeast Saccharomyces cerevisiae belongs to the family of G protein-coupled receptors that contain seven transmembrane domains (TMDs). Because polar residues can influence receptor structure by forming intramolecular contacts between TMDs, we tested the role of the five polar amino acids in TMD6 of the alpha-factor receptor by mutating these residues to nonpolar leucine. Interestingly, a subset of these mutants showed increased affinity for ligand and constitutive receptor activity. The mutation of the most polar residue, Q253L, resulted in 25-fold increased affinity and a 5-fold-higher basal level of signaling that was equal to about 19% of the alpha-factor induced maximum signal. Mutation of the adjacent residue, S254L, caused weaker constitutive activity and a 5-fold increase in affinity. Comparison of nine different mutations affecting Ser254 showed that an S254F mutation caused higher constitutive activity, suggesting that a large hydrophobic amino acid residue at position 254 alters transmembrane helix packing. Thus, these studies indicate that Gln253 and Ser254 are likely to be involved in intramolecular interactions with other TMDs. Furthermore, Gln253 and Ser254 fall on one side of the transmembrane helix that is on the opposite side from residues that do not cause constitutive activity when mutated. These results suggest that Gln253 and Ser254 face inward toward the other TMDs and thus provide the first experimental evidence to suggest the orientation of a TMD in this receptor. Consistent with this, we identified two residues in TMD7 (Ser288 and Ser292) that are potential contact residues for Gln253 because mutations affecting these residues also cause constitutive activity. Altogether, these results identify a new domain of the alpha-factor receptor that regulates its ability to enter the activated conformation.

Recovery of ammonia and phosphate minerals from swine wastewater using gas-permeable membranes.

Gas-permeable membrane technology is useful to recover ammonia (NH3) from liquid manures. In this study, phosphorus (P) recovery via MgCl2 precipitation was enhanced by combining it with NH3 recovery through gas-permeable membranes. Anaerobically digested swine wastewater containing approximately 2300 mg NH4+-N L-1 and 450 mg P L-1 was treated using submerged membranes plus low-rate aeration to recover the NH3 from within the liquid and MgCl2 to precipitate the P. The experiments included a first configuration where N and P were recovered sequentially and a second configuration with simultaneous recovery. The low-rate aeration reduced the natural carbonate, increased pH and accelerated NH3 uptake by the gas-permeable membrane system, which in turn benefited P recovery. Phosphorus removal efficiency was >90% and P recovery efficiency was about 100%. With higher NH3 capture, the recovered P contained higher P2O5 content (37-46%, >98% available), similar to the composition of the biomineral newberyite (MgHPO4·3H2O).

The 80S rat liver ribosome at 25 A resolution by electron cryomicroscopy and angular reconstitution.

BACKGROUND: The ribosome is central to protein synthesis in all living organisms. Single-particle electron cryomicroscopy has recently led to the determination of three-dimensional structures of bacterial ribosomes to approximately 20 A, which have since revolutionised our understanding of ribosomal function. The structure we present here of the 80S rat liver ribosome leads the way to similar progress for mammalian ribosomes. RESULTS: Among the new details revealed by our 25 A structure of the 80S rat liver ribosome are channels within the subunits, a large 'flat ribosomal surface' (FRS) on the outer surface of the large subunit and structural extensions of the mammalian compared to the bacterial ribosome. The main large subunit channel in both the bacterial and the mammalian species starts at the peptidyl transferase centre, below the central protuberance, and ends in the FRS, at the lower back of the large subunit. Structurally, the channels of both species can be directly superimposed. CONCLUSIONS: The mammalian structural extensions--none of which trespass the FRS--can be interpreted in terms of rRNA inserts and additional protein content over that of bacterial ribosomes. The main large subunit channel, which ends at the FRS, is the best candidate for the exit channel for proteins targeted for the endoplasmic reticulum.

The 70S Escherichia coli ribosome at 23 A resolution: fitting the ribosomal RNA.

BACKGROUND: The ribosome--essential for protein synthesis in all organisms--has been an evasive target for structural studies. The best available structures for the 70S Escherichia coli ribosome or its 30S and 50S subunits are based on electron microscopical tilt experiments and are limited in resolution to 28-55 A. The angular reconstitution approach, which exploits the random orientations of particles within a vitreous ice matrix, can be used in conjunction with cryo-electron microscopy to yield a higher-resolution structure. RESULTS: Our 23 A resolution map of the 70S ribosome elucidates many structural details, such as an extensive system of channels within the 50S subunit and an intersubunit gap ideally shaped to accommodate two transfer RNA molecules. The resolution achieved is sufficient to allow the preliminary fitting of double-helical regions of an earlier three-dimensional ribosomal RNA model. CONCLUSIONS: Although we are still a long way from attaining an atomic-resolution structure of the ribosome, cryo-electron microscopy, in combination with angular reconstitution, is likely to yield three-dimensional maps with gradually increasing resolution. As exemplified by our current 23 A reconstruction, these maps will lead to progressive refinement of models of the ribosomal RNA.

Enhancing recovery of ammonia from swine manure anaerobic digester effluent using gas-permeable membrane technology.

Gas-permeable membrane technology is useful to recover ammonia from manure. In this study, the technology was enhanced using aeration instead of alkali chemicals to increase pH and the ammonium (NH4(+)) recovery rate. Digested effluents from covered anaerobic swine lagoons containing 1465-2097 mg NH4(+)-N L(-1) were treated using submerged membranes (0.13 cm(2) cm(-3)), low-rate aeration (120 mL air L-manure(-1) min(-1)) and nitrification inhibitor (22 mg L(-1)) to prevent nitrification. The experiment included a control without aeration. The pH of the manure with aeration rose from 8.6 to 9.2 while the manure without aeration decreased from 8.6 to 8.1. With aeration, 97-99% of the NH4(+) was removed in about 5 days of operation with 96-98% recovery efficiency. In contrast, without aeration it took 25 days to treat the NH4(+). Therefore, the recovery of NH4(+) was five times faster with the low-rate aeration treatment. This enhancement could reduce costs by 70%.

Structure of a molluscan hemocyanin didecamer (HtH1 from Haliotis tuberculata) at 12 A resolution by cryoelectron microscopy.

A 12 A resolution three-dimensional density map of the Haliotis tuberculata hemocyanin type 1 (HtH1) didecamer has been obtained by cryoelectron microscopy of unstained molecules and angular reconstitution. The dyad symmetry of the 8 MDa D5 HtH1 didecamer, formed by the pairing of two asymmetric 4 MDa ring-like C5 decamers, is emphasised. The major and minor surface helical grooves of the didecamer are well defined, in agreement with earlier data on molluscan hemocyanins. The location of the obliquely orientated repeating unit, a subunit dimer, within the decamer has been defined. Following interactive extraction of this dimer, several new structural features of the dimer and of the subunit have now emerged with improved detail. The subunit dimer possesses pseudo 2-fold symmetry, resulting from the steric arrangement of the wall domains/functional units (FUs-abcdef) of the two subunits. The arc and collar FUs (g and h) depart from this inherent 2-fold symmetry and are thereby responsible for the asymmetry of the C5 decamer, with the internalised collar/arc complex at one edge of the decamer. The FU heterodimers forming the wall morphological units have a hollow centre, and thus create a series of repeating channels that extend within the wall through all three tiers of the decamer. The connections between the wall and the arc are defined with improved clarity, and evidence is provided to indicate that the arc and collar FU pairs have a homodimeric composition (gg and hh, respectively). Two possibilities for the subunit path within the subunit dimer are presented, which correlate with the available structural, immunolabelling and protease cleavage data from HtH1 and other molluscan hemocyanins.

Structure of keyhole limpet hemocyanin type 1 (KLH1) at 15 A resolution by electron cryomicroscopy and angular reconstitution.

A three-dimensional reconstruction of keyhole limpet hemocyanin type 1 (KLH1) has been obtained using electron cryomicroscopy at liquid helium temperatures and single particle image processing. The use of a high-contrast embedding medium, 1% (w/v) glucose and 2% (w/v) ammonium molybdate (pH 7.0), enables high-resolution electron micrographs to be recorded close to focus, i.e. with excellent transfer of high-resolution information, while maintaining enough image contrast to localise the individual macromolecules in the images. When low-pass filtered to approximately 45 A resolution, the new 15 A resolution reconstruction is very similar to the earlier reconstructions of gastropodan hemocyanins of specimens embedded in vitreous ice. The map shows much detail and reveals many new symmetry elements in this very large cylindrical molluscan hemocyanin. The full KLH1 didecamer has D5 pointgroup symmetry, yet within the KLH1 decameric half-molecules local 2-fold axes have emerged that make the wall of the KLH1 decamer, in spite of its having an exact C5 symmetry only, resemble the D5-symmetric wall of the decameric cephalopod hemocyanins. In fact, the outside of each tier of this six-tiered gastropodan hemocyanin was found to have an approximate D5 symmetry. Local 2-fold axes also relate the "functional units" within the dimeric "morphological units" of the wall and the collar areas of the 8 MDa KLH1 molecule. Certain local-symmetry-related surface motifs may be present up to 60 times on the outside wall of this highly symmetric cylindrical hemocyanin. Keyhole limpet hemocyanin is used clinically as an immunostimulant. The very strong immune reaction elicited by this hemocyanin may be associated with its intricate hierarchy of local-symmetry components.

Correlation of the expansion segments in mammalian rRNA with the fine structure of the 80 S ribosome; a cryoelectron microscopic reconstruction of the rabbit reticulocyte ribosome at 21 A resolution.

Samples of 80 S ribosomes from rabbit reticulocytes were subjected to electron cryomicroscopy combined with angular reconstitution. A three-dimensional reconstruction at 21 A resolution was obtained, which was compared with the corresponding (previously published) reconstruction of Escherichia coli 70 S ribosomes carrying tRNAs at the A and P sites. In the region of the intersubunit cavity, the principal features observed in the 70 S ribosome (such as the L1 protuberance, the central protuberance and A site finger in the large subunit) could all be clearly identified in the 80 S particle. On the other hand, significant additional features were observed in the 80 S ribosomes on the solvent sides and lower regions of both subunits. In the case of the small (40 S) subunit, the most prominent additions are two extensions at the base of the particle. By comparing the secondary structure of the rabbit 18 S rRNA with our model for the three-dimensional arrangement of E. coli 16 S rRNA, these two extensions could be correlated with the rabbit expansion segments (each totalling ca 170 bases) in the regions of helix 21, and of helices 8, 9 and 44, respectively. A similar comparison of the secondary structures of mammalian 28 S rRNA and E. coli 23 S rRNA, combined with preliminary modelling studies on the 23 S rRNA within the 50 S subunit, enabled the additional features in the 60 S subunit to be sub-divided into five groups. The first (corresponding to a total of ca 335 extra bases in helices 45, 98 and 101) is located on the solvent side of the 60 S subunit, close to the L7/L12 area. The second (820 bases in helices 25 and 38) is centrally placed on the solvent side of the subunit, whereas the third group (totaling 225 bases in helices 18/19, 27/29, 52 and 54) lies towards the L1 side of the subunit. The fourth feature (80 bases in helices 78 and 79) lies within or close to the L1 protuberance itself, and the fifth (560 bases in helix 63) is located underneath the L1 protuberance on the interface side of the 60 S subunit.

Structural organisation of the head-to-tail interface of a bacterial virus.

In tailed icosahedral bacteriophages the connection between the 5-fold symmetric environment of the portal vertex in the capsid and the 6-fold symmetric phage tail is formed by a complex interface structure. The current study provides the detailed analysis of the assembly and structural organisation of such an interface within a phage having a long tail. The region of the interface assembled as part of the viral capsid (connector) was purified from DNA-filled capsids of the Bacillus subtilis bacteriophage SPP1. It is composed of oligomers of gp6, the SPP1 portal protein, of gp15, and of gp16. The SPP1 connector structure is formed by a mushroom-like portal protein whose cap faces the interior of the viral capsid in intact virions, an annular structure below the stem of the mushroom, and a second narrower annulus that is in direct contact with the helical tail extremity. The layered arrangement correlates to the stacking of gp6, gp15, and gp16 on top of the tail. The gp16 ring is exposed to the virion outside. During SPP1 morphogenesis, gp6 participates in the procapsid assembly reaction, an early step in the assembly pathway, while gp15 and gp16 bind to the capsid portal vertex after viral chromosome encapsidation. gp16 is processed during or after tail attachment to the connector region. The portal protein gp6 has 12-fold cyclical symmetry in the connector structure, whereas assembly-naïve gp6 exhibits 13-fold symmetry. We propose that it is the interaction of gp6 with other viral morphogenetic proteins that drives its assembly into the 12-mer state.

Afr1p regulates the Saccharomyces cerevisiae alpha-factor receptor by a mechanism that is distinct from receptor phosphorylation and endocytosis.

The alpha-factor pheromone receptor activates a G protein signaling pathway that induces the conjugation of the yeast Saccharomyces cerevisiae. Our previous studies identified AFR1 as a gene that regulates this signaling pathway because overexpression of AFR1 promoted resistance to alpha-factor. AFR1 also showed an interesting genetic relationship with the alpha-factor receptor gene, STE2, suggesting that the receptor is regulated by Afr1p. To investigate the mechanism of this regulation, we tested AFR1 for a role in the two processes that are known to regulate receptor signaling: phosphorylation and down-regulation of ligand-bound receptors by endocytosis. AFR1 overexpression diminished signaling in a strain that lacks the C-terminal phosphorylation sites of the receptor, indicating that AFR1 acts independently of phosphorylation. The effects of AFR1 overexpression were weaker in strains that were defective in receptor endocytosis. However, AFR1 overexpression did not detectably influence receptor endocytosis or the stability of the receptor protein. Instead, gene dosage studies showed that the effects of AFR1 overexpression on signaling were inversely proportional to the number of receptors. These results indicate that AFR1 acts independently of endocytosis, and that the weaker effects of AFR1 in strains that are defective in receptor endocytosis were probably an indirect consequence of their increased receptor number caused by the failure of receptors to undergo ligand-stimulated endocytosis. Analysis of the ligand binding properties of the receptor showed that AFR1 overexpression did not alter the number of cell-surface receptors or the affinity for alpha-factor. Thus, Afr1p prevents alpha-factor receptors from activating G protein signaling by a mechanism that is distinct from other known pathways.

The immune response and the eye: a role for TNF alpha in anterior chamber-associated immune deviation.

PURPOSE: Interleukin-1 and tumor necrosis factor (TNF) alpha are proinflammatory cytokines and crucial mediators in many aspects of immunity. In this study, their role in anterior chamber-associated immune deviation (ACAID) was investigated. METHODS: The role of these cytokines was examined by the use of neutralizing antibodies to TNF and interleukin (IL)-1 alpha, IL-1 beta, and IL-1 receptor. These reagents were co-injected with antigen into the anterior chamber and the effect on ACAID assessed. In addition, reverse transcriptase polymerase chain reaction (RT-PCR) was performed on eyes injected with TNP-spleen or bovine serum albumin to determine the levels of TNF alpha mRNA induced. RESULTS: Neutralizing antibody to TNF, when injected with TNP-spleen cells into the anterior chamber, blocked ACAID to the TNP hapten. Antibodies to IL-1 alpha, IL-1 beta, and IL-1 receptors either alone or in combination did not block the establishment of ACAID: Studies with reverse transcriptase polymerase chain reaction (Rt-PCR) confirmed that early (within 2 hours) after anterior chamber injection of TNP-cells, messenger RNA levels for TNF alpha were dramatically increased. The induction of ACAID to bovine serum albumin also required the production of TNF alpha. Further studies showed that the production of blood borne "ACAID-inducing" signals after anterior chamber injection of bovine serum albumin or TNP-spleen were dependent on TNF. CONCLUSIONS: TNF alpha plays a crucial role in ACAID: Induction of TNF alpha within the eye may be an important event in the complex series of events that induce ACAID and possibly maintain immunologic privilege.