Measurement of Electron-Neutrino Charged-Current Cross Sections on

Using an 185-kg NaI[Tl] array, COHERENT has measured the inclusive electron-neutrino charged-current cross section on ^{127}I with pion decay-at-rest neutrinos produced by the Spallation Neutron Source at Oak Ridge National Laboratory. Iodine is one the heaviest targets for which low-energy (≤50 MeV) inelastic neutrino-nucleus processes have been measured, and this is the first measurement of its inclusive cross section. After a five-year detector exposure, COHERENT reports a flux-averaged cross section for electron neutrinos of 9.2_{-1.8}^{+2.1}×10^{-40} cm^{2}. This corresponds to a value that is ∼41% lower than predicted using the MARLEY event generator with a measured Gamow-Teller strength distribution. In addition, the observed visible spectrum from charged-current scattering on ^{127}I has been measured between 10 and 55 MeV, and the exclusive zero-neutron and one-or-more-neutron emission cross sections are measured to be 5.2_{-3.1}^{+3.4}×10^{-40} and 2.2_{-0.5}^{+0.4}×10^{-40} cm^{2}, respectively.

A packaged intervention to improve viral load monitoring within a deeply rural health district of South Africa.

BACKGROUND: The KwaZulu-Natal (KZN) province of South Africa has the highest prevalence of HIV infection in the world. Viral load (VL) testing is a crucial tool for clinical and programmatic monitoring. Within uMkhanyakude district, VL suppression rates were 91% among patients with VL data; however, VL performance rates averaged only 38·7%. The objective of this study was to determine if enhanced clinic processes and community outreach could improve VL monitoring within this district. METHODS: A packaged intervention was implemented at three rural clinics in the setting of the KZN HIV AIDS Drug Resistance Surveillance Study. This included file hygiene, outreach, a VL register and documentation revisions. Chart audits were used to assess fidelity. Outcome measures included percentage VL performed and suppressed. Each rural clinic was matched with a peri-urban clinic for comparison before and after the start of each phase of the intervention. Monthly sample proportions were modelled using quasi-likelihood regression methods for over-dispersed binomial data. RESULTS: Mkuze and Jozini clinics increased VL performance overall from 33·9% and 35·3% to 75·8% and 72·4%, respectively which was significantly greater than the increases in the comparison clinics (RR 1·86 and 1·68, p < 0·01). VL suppression rates similarly increased overall by 39·3% and 36·2% (RR 1·84 and 1·70, p < 0·01). The Chart Intervention phase showed significant increases in fidelity 16 months after implementation. CONCLUSIONS: The packaged intervention improved VL performance and suppression rates overall but was significant in Mkuze and Jozini. Larger sustained efforts will be needed to have a similar impact throughout the province.

Scintillation characteristics of the EJ-299-02H scintillator.

A study of the dead layer thickness and quenching factor of a plastic scintillator for use in ultracold neutron (UCN) experiments is described. Alpha spectroscopy was used to determine the thickness of a thin surface dead layer to be 630 ± 110 nm. The relative light outputs from the decay of 241Am and Compton scattering of electrons were used to extract Birks' law coefficient, yielding a kB value of 0.087 ± 0.003 mm/MeV, consistent with some previous reports for other polystyrene-based scintillators. The results from these measurements are incorporated into the simulation to show that an energy threshold of (∼9 keV) can be achieved for the UCNProBe experiment. This low threshold enables high beta particle detection efficiency and the indirect measurement of UCN. The ability to make the scintillator deuterated, accompanied by its relatively thin dead layer, gives rise to unique applications in a wide range of UCN experiments, where it can be used to trap UCN and detect charged particles in situ.

Copy number variation in pediatric multiple sclerosis.

BACKGROUND: Pediatric onset multiple sclerosis (MS) accounts for 2-4% of all MS. It is unknown whether the disease shares the same underlying pathophysiology found in adult patients or an extreme early onset phenotype triggered by distinct biological mechanisms. It has been hypothesized that copy number variations (CNVs) may result in extreme early onset diseases because CNVs can have major effects on many genes in large genomic regions. OBJECTIVES AND METHODS: The objective of the current research was to identify CNVs, with a specific focus on de novo CNVs, potentially causing early onset MS by competitively hybridizing 30 white non-Hispanic pediatric MS patients with each of their parents via comparative genomic hybridization (CGH) analysis on the Agilent 1M CGH array. RESULTS AND DISCUSSION: We identified 10 CNVs not overlapping with any CNV regions currently reported in the Database of Genomic Variants (DGV). Fifty-five putatively de novo CNVs were also identified: all but one common in the DGV. We found the single rare CNV was a private variation harboring the SACS gene. SACS mutations cause autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) disease. Additional clinical review revealed that the patient with the SACS gene CNV shared some features of both MS and ARSACS. CONCLUSIONS: This is the first reported study analyzing pediatric MS CNVs. While not yielding causal variation in our initial pediatric dataset, our approach confirmed diagnosis of an ARSACS-like disease in addition to MS in the affected individual, which led to a more complete understanding of the patient's disease course and prognosis.

Multilevel analysis of the Be Active Eat Well intervention: environmental and behavioural influences on reductions in child obesity risk.

BACKGROUND: The Be Active Eat Well (BAEW) community-based child obesity prevention intervention was successful in modestly reducing unhealthy weight gain in primary school children using a multi-strategy and multi-setting approach. OBJECTIVE: To (1) examine the relationship between changes in obesity-related individual, household and school factors and changes in standardised child body mass index (zBMI), and (2) determine if the BAEW intervention moderated these effects. METHODS: The longitudinal relationships between changes in individual, household and school variables and changes in zBMI were explored using multilevel modelling, with measurement time (baseline and follow-up) at level 1, individual (behaviours, n = 1812) at level 2 and households (n = 1318) and schools (n = 18) as higher levels (environments). The effect of the intervention was tested while controlling for child age, gender and maternal education level. RESULTS: This study confirmed that the BAEW intervention lowered child zBMI compared with the comparison group (-0.085 units, P = 0.03). The variation between household environments was found to be a large contributor to the percentage of unexplained change in child zBMI (59%), compared with contributions from the individual (23%) and school levels (1%). Across both groups, screen time (P = 0.03), sweet drink consumption (P = 0.03) and lack of household rules for television (TV) viewing (P = 0.05) were associated with increased zBMI, whereas there was a non-significant association with the frequency the TV was on during evening meals (P = 0.07). The moderating effect of the intervention was only evident for the relationship between the frequency of TV on during meals and zBMI, however, this effect was modest (P = 0.04). CONCLUSIONS: The development of childhood obesity involves multi-factorial and multi-level influences, some of which are amenable to change. Obesity prevention strategies should not only target individual behaviours but also the household environment and family practices. Although zBMI changes were modest, these findings are encouraging as small reductions can have population level impacts on childhood obesity levels.

Ultracold neutron properties of the Eljen-299-02D deuterated scintillator.

In this paper, we report studies of the Fermi potential and loss per bounce of ultracold neutrons (UCNs) on a deuterated scintillator (Eljen-299-02D). These UCN properties of the scintillator enable its use in a wide variety of applications in fundamental neutron research.

Multiple sclerosis susceptibility alleles in African Americans.

Multiple sclerosis (MS) is an autoimmune demyelinating disease characterized by complex genetics and multifaceted gene-environment interactions. Compared to whites, African Americans have a lower risk for developing MS, but African Americans with MS have a greater risk of disability. These differences between African Americans and whites may represent differences in genetic susceptibility and/or environmental factors. SNPs from 12 candidate genes have recently been identified and validated with MS risk in white populations. We performed a replication study using 918 cases and 656 unrelated controls to test whether these candidate genes are also associated with MS risk in African Americans. CD6, CLEC16a, EVI5, GPC5, and TYK2 contained SNPs that are associated with MS risk in the African American data set. EVI5 showed the strongest association outside the major histocompatibility complex (rs10735781, OR=1.233, 95% CI=1.06-1.43, P-value=0.006). In addition, RGS1 seems to affect age of onset whereas TNFRSF1A seems to be associated with disease progression. None of the tested variants showed results that were statistically inconsistent with the effects established in whites. The results are consistent with shared disease genetic mechanisms among individuals of European and African ancestry.

Comparative analyses of published cost effectiveness models highlight critical considerations which are useful to inform development of new models.

Background: Comparative analyses of published cost effectiveness models provide useful insights into critical issues to inform the development of new cost effectiveness models in the same disease area.Objective: The purpose of this study was to describe a comparative analysis of cost-effectiveness models and highlight the importance of such work in informing development of new models. This research uses genotypic antiretroviral resistance testing after first line treatment failure for Human Immunodeficiency Virus (HIV) as an example.Method: A literature search was performed, and published cost effectiveness models were selected according to predetermined eligibility criteria. A comprehensive comparative analysis was undertaken for all aspects of the models.Results: Five published models were compared, and several critical issues were identified for consideration when developing a new model. These include the comparator, time horizon and scope of the model. In addition, the composite effect of drug resistance prevalence, antiretroviral therapy efficacy, test performance and the proportion of patients switching to second-line ART potentially have a measurable effect on model results. When considering CD4 count and viral load, dichotomizing patients according to higher cost and lower quality of life (AIDS) versus lower cost and higher quality of life (non-AIDS) status will potentially capture differences between resistance testing and other strategies, which could be confirmed by cross-validation/convergent validation. A quality adjusted life year is an essential outcome which should be explicitly explored in probabilistic sensitivity analysis, where possible.Conclusions: Using an example of GART for HIV, this study demonstrates comparative analysis of previously published cost effectiveness models yields critical information which can be used to inform the structure and specifications of new models.

Selective cervical nerve root blockade: experience with a safe and reliable technique using an anterolateral approach for needle placement.

BACKGROUND AND PURPOSE: [corrected] Our aim was to evaluate the safety and clinical utility of a fluoroscopically guided anterolateral oblique approach technique for outpatient diagnostic and therapeutic selective cervical nerve root blockade (SCNRB). MATERIALS AND METHODS: During a 13-year period (1994 through February 2007), 4612 patients underwent fluoroscopically guided diagnostic and/or therapeutic extraforaminal SCNRB by using an anterior oblique approach at affiliated outpatient imaging centers. Each procedure was performed by 1 of 6 procedural radiologists, all highly experienced in and actively performing spinal injections on a full-time basis in clinical practice. All of the proceduralists were thoroughly experienced with lumbar injections before endeavoring to perform SCNRBs. Nonionic contrast was injected in nearly all patients (except isolated patients with contrast allergy), and a minimum of 2 projection filming procedures were performed to document the accuracy of needle placement and contrast dispersal before the injection of therapeutic substances. All clinically significant complications beyond skin discoloration and temporary exacerbation of symptoms were recorded. RESULTS: There were no serious neurologic complications, such as stroke, spinal cord insult, or permanent nerve root deficit. One life-threatening anaphylactic reaction occurred and was attributed to the injected materials and not the specific procedure itself. Another patient had a 3- to 4-minute grand mal seizure, from which he fully recovered within 30 minutes. There were no infections. CONCLUSION: The technique we describe for fluoroscopically guided SCNRB is a useful and safe outpatient procedure when performed by skilled and experienced proceduralists.

Diskography: infectious complications from a series of 12,634 cases.

BACKGROUND AND PURPOSE: Diskography is commonly performed to investigate pain of suspected diskogenic origin. Although uncommon, diskitis is a feared complication of this procedure. We reviewed the incidence of diskitis and other infectious complications following diskography in a large busy outpatient practice and discuss technical aspects that may contribute to infection prevention. METHODS: We reviewed the electronic records of all diskograms obtained at our institution during a 12.25-year period, looking for all cases of procedure-related infection. All diskograms had been obtained by skilled and experienced procedural radiologists in dedicated spine-injection suites with specialized technical staff. RESULTS: There were 12,634 examinations performed on 10,663 patients for a total of 37,135 disk levels. Of the disk levels, 5981 were cervical; 3083, thoracic; and 28,071, lumbar. Two cases of confirmed lumbar diskitis and no cases of either cervical or thoracic diskitis were seen in our series. No other infectious complications were found. The incidence of diskitis was 0.016% per examination and 0.0054% per disk level. CONCLUSION: In skilled and experienced hands using proper technique, diskography is a safe outpatient procedure with an extremely low incidence of diskitis and other procedure-related infections.

Comparison of adriamycin uptake in chick embryo heart and liver cells an murine L5178Y lymphoblasts in vitro: role of drug uptake in cardiotoxicity.

The mechanism of uptake of Adriamycin was investigated in chick embryo heart and liver cells and in murine L5178Y lymphoblasts in vitro. Drug uptake at 4 degrees C for 15 s due to rapid association accounted for a cell:medium distribution ratio of 104 +/- 14 (SE) in heart cells, 10.2 +/- 1.3 in liver cells, and 10.3 +/- 1.5 in L5178Y lymphoblasts. On thin-layer chromatographic analysis, 98% of the radioactivity migrated with the mobility of intact drug, suggesting that drug metabolism was negligible for at least 30 min in both heart and tumor cells. A time course of drug uptake was somewhat different in heart cells compared to that noted for liver or L5178Y cells. The steady state for drug uptake was reached more promptly in heart cells; apparent equilibrium was observed at 6 min in heart cells, at approximately 20 min in L5178Y lymphoblasts, but was not attained by 25 min in liver cells. Temperature dependence of drug uptake also differed in the three cell types; drug uptake was most temperature sensitive in L5178Y cells, intermediate in liver cells, and least temperature dependent in heart cells. Separation of heart, liver, and leukemic cells into membrane and cytosol fractions demonstrated that, at 1 and 30 min, more than 75% of the drug was associated with the membrane fraction. Trichloroacetic acid extraction of cell constituents revealed that, at 1 min, the acid-soluble fraction amounted to 32 +/- 2% of radioactivity in heart cells and 37 +/- 2% in L5178Y cells. Ethanol extraction of these cells demonstrated that, at 1 min, ethanol-soluble components accounted for 49 +/- 2% of radioactivity in heart cells and 27 +/- 2% in leukemic cells. The finding of a large component of rapid association together with evidence of prompt drug binding to cellular constituents made evaluation of unidirectional drug influx impractical. Accordingly, an investigation was undertaken of Adriamycin efflux from chick embryo heart and liver cells and L5178Y lymphoblasts, after the cells had been loaded with drug for various time intervals. In all three cell types, efflux was rapid down to a plateau level, representing nonexchangeable drug. As the period of time for loading cells was increased, there was a progressive rise in the level of nonexchangeable drug. Equilibration of the nonexchangeable pool occurred more rapidly in heart cells than in either liver or leukemic cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Long, intrinsic horizontal axons radiating through and beyond rat barrel cortex have spatial distributions similar to horizontal spreads of activity evoked by whisker stimulation.

Stimulation of a single whisker evokes a peak of activity that is centered over the associated barrel in rat primary somatosensory cortex, and yet the evoked local field potential and the intrinsic signal optical imaging response spread symmetrically away from this barrel for over 3.5 mm to cross cytoarchitectonic borders into other "unimodal" sensory cortical areas. To determine whether long horizontal axons have the spatial distribution necessary to underlie this activity spread, we injected adeno-associated viral vectors into barrel cortex and characterized labeled axons extending from the injection site in transverse sections of flattened cortex. Combined qualitative and quantitative analyses revealed labeled axons radiating diffusely in all directions for over 3.5 mm from supragranular injection sites, with density declining over distance. The projection pattern was similar at four different cortical depths, including infragranular laminae. Infragranular vector injections produced patterns similar to the supragranular injections. Long horizontal axons were detected both using a vector with a permissive cytomegalovirus promoter to label all neuronal subtypes and using a calcium/calmodulin-dependent protein kinase II α vector to restrict labeling to excitatory cortical pyramidal neurons. Individual axons were successfully reconstructed from series of supragranular sections, indicating that they traversed gray matter only. Reconstructed axons extended from the injection site, left the barrel field, branched, and sometimes crossed into other sensory cortices identified by cytochrome oxidase staining. Thus, radiations of long horizontal axons indeed have the spatial characteristics necessary to explain horizontal activity spreads. These axons may contribute to multimodal cortical responses and various forms of cortical neural plasticity.

Similar but distinct effects of the tristetraprolin/TIS11 immediate-early proteins on cell survival.

The immediate early protein tristetraprolin (TTP) is required to prevent inappropriate production of the cytokine TNF-alpha, and is a member of a zinc finger protein family that is associated with RNA binding. TTP expression is induced by TNF-alpha, and evidence indicates that TTP can bind and destabilize the TNF-alpha mRNA. TTP and the closely related TIS11b and TIS11d proteins are evolutionarily conserved, however, and induced transiently in various cell types by numerous diverse stimuli, suggesting that they have additional functions. Supporting this idea, continuous expression of each TTP/TIS11 protein at physiological levels causes apoptotic cell death. By various criteria, this cell death appears analogous to apoptosis induced by certain oncoproteins. It is also dependent upon the zinc fingers, suggesting that it involves action on appropriate cellular targets. TTP but not TIS11b or TIS11d also sensitizes cells to induction of apoptosis by TNF-alpha. The data suggest that the TTP and TIS11 immediate early proteins have similar but distinct effects on growth or survival pathways, and that TTP might influence TNF-alpha regulation at multiple levels.

Perceptual correlates of neural representations evoked by odorant enantiomers.

Spatial activation patterns within the olfactory bulb are believed to contribute to the neural representation of odorants. In this study, we attempted to predict the perceptions of odorants from their evoked patterns of neural activity in the olfactory bulb. We first describe the glomerular activation patterns evoked by pairs of odorant enantiomers based on the uptake of [(14)C]2-deoxyglucose in the olfactory bulb glomerular layer. Using a standardized data matrix enabling the systematic comparison of these spatial odorant representations, we hypothesized that the degree of similarity among these representations would predict their perceptual similarity. The two enantiomers of carvone evoked overlapping but significantly distinct regions of glomerular activity; however, the activity patterns evoked by the enantiomers of limonene and of terpinen-4-ol were not statistically different from one another. Commensurate with these data, rats spontaneously discriminated between the enantiomers of carvone, but not between the enantiomers of limonene or terpinen-4-ol, in an olfactory habituation task designed to probe differences in olfactory perception.

Determination of L-lactate binding stoichiometry and differences in allosteric interactions of structurally distinct homohexamers from Panulirus interruptus hemocyanin.

The role of structurally distinct subunits from the hemocyanin of Panulirus interruptus was investigated by the analysis of the oxygen-binding properties of reassembled homohexamers. Homohexamers reassembled from subunits a and b exhibited cooperative oxygen binding, whereas subunit c did not. The oxygen affinity of homohexamers from subunits b and c was specifically increased by the addition of L-lactate, whereas that of subunit a was not. Both native hexamers and the homohexamers from subunit b have approximately one oxygen-linked lactate binding site per hexamer.

Ligand-induced stabilization of PPARgamma monitored by NMR spectroscopy: implications for nuclear receptor activation.

Nuclear receptors are ligand-dependent transcription factors that are mediators of the action of lipophilic hormones and other endogenous ligands and are the targets of drugs useful in a variety of therapeutic areas. Peroxisome proliferator-activated receptor (PPAR)gamma is a nuclear receptor that, acting as a heterodimer with RXR, mediates a variety of cellular effects including adipocyte-differentiation. Due to its role in modulating insulin sensitivity, it is the target of therapeutically active anti-diabetic agents such as rosiglitazone. We have assigned the chemical shifts of the backbone atoms of the 32 kDa ligand-binding domain of PPARgamma in the presence of bound rosiglitazone. Three-dimensional HNCO spectra of the apo ligand-binding domain (LBD) have less than half the expected number of cross-peaks. The missing cross-peaks are restored upon binding strong agonists such as rosiglitazone. The NMR results indicate that the apo-LBD of PPARgamma is in a conformationally mobile state, and that agonist binding is associated with a marked stabilization of the conformation. Mapping the missing peaks to the 3D X-ray crystallographic structure indicates the region of mobility is extensive and includes the ligand-binding region and the cofactor-binding site. This leads to the conclusion that activation of this nuclear receptor is a result of a population shift of a dynamic ensemble of conformations, rather than a two-state switch from an inactive to an active conformation. Our results have important implications for the mechanisms by which antagonists, partial agonists, and agonists of nuclear receptor function operate.

Suicidal behavior runs in families. A controlled family study of adolescent suicide victims.

BACKGROUND: While previous studies have shown an increased rate of suicidal behavior in the relatives of suicide victims, it is unclear if this is attributable merely to increased familial rates of psychiatric disorders. Therefore, we conducted a family study of adolescent suicide victims (suicide probands) and community control probands (controls) to determine if the rates of suicidal behavior were higher in the relatives of adolescent suicide probands even after adjusting for differences in the familial rates of psychiatric disorders. METHOD: The relatives of 58 adolescent suicide probands and 55 demographically similar controls underwent assessment for Axis I and II psychiatric disorders, lifetime history of aggression, and history of suicidal behavior (attempts and completions) using a combination of family study and family history approaches. RESULTS: The rate of suicide attempts was increased in the first-degree relatives of suicide probands compared with the relatives of controls, even after adjusting for differences in rates of proband and familial Axis I and II disorders (odds ratio, 4.3; 95% confidence intervals, 1.1-16.6). On the other hand, the excess rate of suicidal ideation found in the relatives of suicide probands was explained by increased familial rates of psychiatric disorders. Among suicide probands, higher ratings of aggression were associated with higher familial loading for suicide attempts. CONCLUSIONS: Liability to suicidal behavior might be familially transmitted as a trait independent of Axis I and II disorders. The transmitted spectrum of suicidal behavior includes attempts and completions, but not ideation, and the transmission of suicidal behavior and aggression are related.

A clinical psychotherapy trial for adolescent depression comparing cognitive, family, and supportive therapy.

BACKGROUND: Previous studies in nonclinical samples have shown psychosocial treatments to be efficacious in the treatment of adolescent depression, but few psychotherapy treatment studies have been conducted in clinically referred, depressed adolescents. METHODS: One hundred seven adolescent patients with DSM-III-R major depressive disorder (MDD) were randomly assigned to 1 of 3 treatments: individual cognitive behavior therapy, systemic behavior family therapy (SBFT), or individual nondirective supportive therapy (NST). Treatments were 12 to 16 sessions provided in as many weeks. Intent-to-treat analyses were conducted using all follow-up data. RESULTS: Of the 107 patients enrolled in the study, 78 (72.9%) completed the study, 4 (3.7%) never initiated treatment, 10 (9.3%) had exclusionary criteria that were undetected at entry, 8 (7.5%) dropped out, and 7 (6.5%) were removed for clinical reasons. Cognitive behavior therapy showed a lower rate of MDD at the end of treatment compared with NST (17.1% vs 42.4%; P = .02), and resulted in a higher rate of remission (64.7%, defined as absence of MDD and at least 3 consecutive Beck Depression Inventory scores < 9) than SBFT (37.9%; P = .03) or NST (39.4%; p = .04). Cognitive behavior therapy resulted in more rapid relief in interviewer-rated (vs both treatments, P = .03) and self-reported depression (vs SBFT, P = .02). All 3 treatments showed significant and similar reductions in suicidality and functional impairment. Parents' views of the credibility of cognitive behavior therapy improved compared with parents' views of both SBFT (P = .01) and NST (P = .05). CONCLUSIONS: Cognitive behavior therapy is more efficacious than SBFT or NST for adolescent MDD in clinical settings, resulting in more rapid and complete treatment response.

Effect of reduction and alkylation on structure and function of rabbit IgG antibody--II. Effects on classical pathway C3 convertase formation.

Anaerobic reduction of purified rabbit IgG antibody (Ab) with 1.5 moles of dithiothreitol per mole of Ab at pH 8.0, followed by alkylation, cleaves 39% of the inter-heavy-chain (H-H) disulfide (SS) bonds. This treatment has the following effects on the ability of the Ab to activate the classical pathway of complement. Compared to control Ab, reduced and alkylated (RA) Ab retained 4-5.6% of overall hemolytic activity and 55% of complement-fixing activity at 0 degrees C. Complexes of RA Ab and equivalent amounts of soluble Ag consumed C4, C2 and C3 at 37, 51 and 44%, respectively, of the rate at which these components were consumed by equal concns of complexes containing control Ab. Complexes made with RA Ab bound 18% as much C-1 as those made with native Ab. These data indicate that the principal, if not the only, effect of RA is on C-1 binding. Measurements of the ability of complexes of Ab with cell-bound Ag to bind C-1 showed at most a 20% loss of C-1 binding sites and a ca two-fold decrease in affinity for C-1. Similar results were obtained with purified (activated) C-1 and with native C1 in serum. No significant difference could be detected in the rate of activation of bound C1. Normal rabbit IgG which was reduced and alkylated under the same conditions retained 52% of its H-H SS bonds and 30% of its ability to bind C-1. This finding suggests that the impairment in C-1 binding results from an effect on the C1 binding site itself, rather than from an effect on the ability of the RA Ab to transmit a putative conformational "signal" from the Ag-binding site to the C1 binding site. Finally, our data show that the observed functional effect of reduction and alkylation depends strongly on the assay used to evaluate that effect.

8-Methoxypsoralen levels in blood of vitiligo patients and in skin, ophthalmic fluids, and ocular tissues of the guinea pig.

8-Methoxypsoralen (8-MOP) levels in the blood of vitiligo patients were determined through the use of a reverse-phase high-performance liquid chromatographic method. The overall recovery of the internal standards was 85-94%, with the lower detection limit of 8-MOP at 2 ng. Peak blood levels as low as 130 ng/ml and as high as 3892 ng/ml were obtained in patients at 1-3 h following the oral administration of 0.6 mg/kg body weight of Oxsoralen capsules (Elder Pharmaceuticals Co.). These results are consistent with the clinical observation that maximum response in phototherapy is obtained at about 2 h after oral administration of the drug. Two hours after oral administration of 0.6 mg/kg of Oxsoralen, 8-MOP levels in the epidermis, dermis, and whole skin of the guinea pig (in ng/g) were: epidermis, 330 +/- 20; dermis, 89 +/- 16; whole skin, 379 +/- 19. Also detected were 8-MOP levels of 441 +/- 22 ng/ml in aqueous humor, 166 +/- 18 ng/ml in vitreous gel, 355 +/- 15 ng/g in lens, and 410 +/- 26 ng/g in retina. These results point to the fact that the eyes of the patient must be protected from exposure to sunlight after psoralen UV treatment, and that 8-MOP is absorbed in blood unevenly and varies from patient to patient. The fact that only 50-60% of the patients responded to psoralen photochemotherapy for vitiligo may be related to the variation of absorption of the drug in individual patients.