KIR2DL4-HLAG interaction at human NK cell-oligodendrocyte interfaces regulates IFN-γ-mediated effects.

Interactions between germline-encoded natural killer (NK) cell receptors and their respective ligands on tumorigenic or virus-infected cells determine NK cell cytotoxic activity and/or cytokine secretion. NK cell cytokine responses can be augmented in and can potentially contribute to multiple sclerosis (MS), an inflammatory disease of the central nervous system focused upon the oligodendrocytes (OLs). To investigate mechanisms by which NK cells may contribute to MS pathogenesis, we developed an in vitro human model of OL-NK cell interaction. We found that activated, but not resting human NK cells form conjugates with, and mediate cytotoxicity against, human oligodendrocytes. NK cells, when in conjugate with OLs, rapidly synthesize and polarize IFN-γ toward the OLs. IFN-γ is capable of reducing myelin oligodendrocyte and myelin associated glycoproteins (MOG and MAG) content. This activity is independent of MHC class-I mediated inhibition via KIR2DL1, but dependent upon the interaction between NK cell-expressed KIR2DL4 and its oligodendrocyte-expressed ligand, HLA-G. NK cells from patients with MS express higher levels of IFN-γ following conjugation to OLs, more actively promote in vitro reduction of MOG and MAG and have higher frequencies of the KIR2DL4 positive population. These data collectively suggest a mechanism by which NK cells can promote pathogenic effects upon OLs.

Static and dynamic electro-optical properties of liquid crystals mediated by ferroelectric polymer films.

This paper reports the electro-optical properties of high resistivity nematic liquid crystals sandwiched between ferroelectric polymer films. Interactions between liquid crystals and the film result in a series of interesting optical and electro-optical features. For example, the visualization of ferroelectric domains by means of liquid crystals has been known for decades. However, here we demonstrate that liquid crystals can also reveal the fractal dimension of multi-domain poly(vinylidene fluoride)-based films. Unidirectionally rubbed films made of poly(vinylidene fluoride)-based (PVDF) materials align liquid crystals (LC) homogeneously, with the pretilt angle on the order of 1-2 degrees. This property was implemented in the design of hybrid cells composed of liquid crystals sandwiched between PVDF-based films. The designed PVDF|LC|PVDF cells exhibit tunable electro-optical performance originating from the presence of the PVDF-based films. More specifically, (i) the threshold voltage characterizing the transition of liquid crystals from a planar to a homeotropic state can be tuned by varying the film thickness, and (ii) total fall time (turn-off time) can be controlled by varying the frequency and amplitude of the driving voltage. This frequency dependence of the fall time is strongly pronounced at a relatively high voltage applied across the cell. In the low frequency regime, an increase in the turn-off time can be approximated as a linear function of the applied electric field. An electric-field induced polarization of the PVDF-based films is considered a major reason leading to the afore-mentioned amplitude and frequency dependence of the switching time.

Photorefractive two-beam coupling joint transform correlator: modeling and performance evaluation.

The photorefractive two-beam coupling joint transform correlator combines two features. The first is embedded semi-adaptive optimality, which weighs the correlation against clutter and noise in the input, and the second is the intrinsic dynamic range compression nonlinearity, which improves several metrics simultaneously without metric trade-off. Although the two beam coupling correlator was invented many years ago, its outstanding performance was recognized on only relatively simple images. There was no study about the performance of this correlator on complicated images and using different figures of merit. In this paper, the study is extended to more complicated images. For the first time, to our knowledge, we demonstrate simultaneous improvement in metrics performance without metric trade-off. The performance was evaluated compared to the classical joint transform correlator. A typical experimental result to validate the simulation results was also shown in this work. The best performing operation parameters were identified to guide the experimental work and for future comparison with other well-known optimal correlation filters.

Holographic assessment of self-phase modulation and blooming in a thermal medium.

The use of a low-power laser beam to characterize self-phase modulation (SPM) and bubble formation during thermal blooming (TB), as well as manipulation of the bubbles, is reported. First, a low-power 633 nm laser beam is used to characterize the induced refractive index profile during SPM of a focused 514 nm pump beam in absorbing liquid media, e.g., a solution of red dye in isopropyl alcohol. The induced phase change is also characterized using digital holography via the 633 nm source as the probe and reference. During TB at higher pump powers, bubble formation occurs in the liquid. Using a modified setup, which minimizes the effects of gravity, buoyancy, and convection, stable bubbles are generated. These are characterized using in-line digital holography with the 633 nm probe beam. It is shown that the bubble size depends on exposure time of the pump and that the bubble can be steered by moving a focused low-power laser beam. Finally, possible applications of these thermally generated bubbles are discussed.

Holographic volume displacement calculations via multiwavelength digital holography.

In this work multiwavelength digital holography is applied to calculate the volume displacement of various topographic surface features. To accurately measure the volume displacement of macroscopic features, long synthetic wavelengths up to several millimeters are generated using tunable IR laser sources. Practical methods of implementation are considered, including geometric effects of both Michelson and Mach-Zehnder recording configurations and error due to wavelength selection.

Achieving enhanced gain in photorefractive polymers by eliminating electron contributions using large bias fields.

Photorefractive polymers have been extensively studied for over two decades and have found applications in holographic displays and optical image processing. The complexity of these materials arises from multiple charge contributions, for example, leading to the formation of competing photorefractive gratings. It has been recently shown that in a photorefractive polymer at relatively moderate applied electric fields the primary charge carriers (holes) establish an initial grating, followed by a subsequent competing grating (electrons) resulting in a decreased two-beam coupling and diffraction efficiencies. In this paper, it is shown that with relatively large sustainable bias fields, the two-beam coupling efficiency is enhanced owing to a decreased electron contribution. These results also explain the cause of dielectric breakdown experienced under large bias fields. Our conclusions are supported by self-pumped transient two-beam coupling and photocurrent measurements as a function of applied bias fields at different wavelengths.

Co-sputtered SiC + Ag nanomixtures as visible wavelength negative index metamaterials.

The fabrication and characterization of a novel metamaterial that shows negative index in the visible (blue) is reported. The real part of the negative index of this metamaterial at 405 nm, comprising co-sputtered SiC + Ag nanoparticle mixture on a glass substrate, is deduced from results of double Michelson interferometry setup which shows a negative phase delay. It is numerically verified that this metamaterial can yield near-field super-resolution imaging for both TE and TM polarizations.

Asymmetric Freedericksz transitions from symmetric liquid crystal cells doped with harvested ferroelectric nanoparticles.

The electrical Freedericksz transition characteristics of planar aligned liquid crystal cells doped with harvested single ferroelectric domain 9 nm nanoparticles of BaTiO(3) have been measured. We demonstrate for the first time that the electrical pre-history of the cells imparts significant polarity sensitivity to the Freedericksz characteristics. The presence of harvested single domain ferroelectric nanoparticles enables cells to be programmably semi-permanently polarized. This reduces or increases the Freedericksz transition threshold by 0.8 V, depending on the polarity of the applied voltage, giving a net 1.6 V Freedericksz threshold asymmetry for 8 mum thick cells filled with TL205 liquid crystal.

Stimulated photorefractive backscatter leading to six-wave mixing and phase conjugation in iron-doped lithium niobate.

The generation of multiple waves during near-oblique incidence of a 532 nm weakly focused beam on photorefractive iron-doped lithium niobate in a typical reflection geometry configuration is studied. It is shown that these waves are produced through two-wave coupling (self-diffraction) and four-wave mixing (parametric diffraction). One of these waves, the stimulated photorefractive backscatter produced from parametric diffraction, contains the self-phase conjugate. The dynamics of six-wave mixing and its dependence on crystal parameters, angle of incidence, and pump power are analyzed. What we believe to be a novel order analysis of the interaction equations provides further insight into experimental observations in the steady state. The quality of the backscatter is evaluated through image restoration, interference experiments, and visibility measurement. Reduction of two-wave coupling may significantly improve the quality of the self-phase conjugate.

Increased androgen receptor expression correlates with development of age-dependent, lobe-specific spontaneous hyperplasia of the brown Norway rat prostate.

Androgens are essential for development and differentiated function, as well as proliferation and survival of cells within the prostate gland. Age-related changes in the hormonal milieu, marked by a decrease in the serum androgen to estrogen ratio may contribute to the evolution of pathological changes, such as benign prostatic hyperplasia and carcinoma of the prostate gland, in older men. A similar phenomenon occurs in Brown Norway rats, in which the serum testosterone to estradiol ratio declines with age, and despite the lower serum testosterone level, age-dependent prostatic hyperplasia develops in the dorsal and lateral lobes, but not in the ventral lobe. To evaluate a role for changes in androgen action in the evolution of prostatic hyperplasia, we compared the immunostaining intensity of androgen receptor in the different prostate lobes from young (4 months of age) and old (24 months of age) Brown Norway rats. Androgen receptor immunostaining was present in the nuclei of all epithelial cells and some stromal cells throughout the prostatic ducts of each lobe from both young and old rats. Whereas androgen receptor immunostaining intensity decreased in luminal epithelial cells of the ventral prostate from old rats, it increased in luminal epithelial cells of the dorsal and lateral lobes from old rats, when compared with young rats. To validate immunocytochemical studies, Western blot analyses were performed. The total tissue level of androgen receptor decreased by 30% in the ventral lobe of old rats, whereas tissue levels of androgen receptor increased 2.7-fold and 1.3-fold in the dorsal and lateral lobes, respectively, of old rats. Similarly, the percentage of epithelial cells staining positive for the proliferation marker, proliferating cell nuclear antigen, was increased approximately 2-fold in the dorsal and lateral lobes as a function of older age. The presence of higher levels of androgen receptor and increased number of proliferating cell nuclear antigen-positive cells in the dorsal and lateral lobes of old rats suggest that changes in androgen receptor levels may be related to the lobe-specific proliferation of cells that occurs with increasing age. Additional evidence for lobe-specific regulation of androgen receptor expression was obtained from Western blots and by immunocytochemistry following castration. Androgen receptor levels in the ventral and dorsal lobes, but not the lateral lobe, of young and old rats were down-regulated in the absence of testicular androgen. However, nuclear immunostaining of androgen receptor returned by 7-10 d after castration in the ventral and dorsal lobes in the continued absence of androgen. Moreover, up-regulation of the androgen receptor level occurred more rapidly in the ventral and dorsal lobes of old, compared with young, castrated rats. Taken together, these results suggest that lobe-specific and age-dependent differences in the regulation of androgen receptor expression might lead to changes in tissue androgen responsiveness and the consequent development of lobe-specific hyperplasia in the Brown Norway rat prostate gland.

Convergence of electromagnetic field components across discontinuous premittivity profiles.

We provide further insight into why the inverse rule [J. Opt. Soc. Am. A 13, 1870 (1996)] for multiplying two finite Fourier series of two pairwise discontinuous functions yields correct results at the point of discontinuity.

Castration-induced apoptotic cell death in the Brown Norway rat prostate decreases as a function of age.

Growth and differentiation of the prostate gland depends upon androgens, yet overgrowth of the human prostate occurs later in life when serum levels of testosterone are declining. We have reported a similar phenomenon in the Brown Norway rat, but the age-dependent overgrowth of the prostate is confined to the dorsal and lateral lobes and, hence, is lobe specific. Because tissue growth depends upon the balance between proliferation and death of cells, the present study was designed to investigate whether cell death differed in the various prostatic lobes of Brown Norway rats as a function of age. Apoptosis of cells in the ventral, dorsal, lateral, and anterior lobes of the prostate was examined in young (4-month-old) and old (24-month-old) Brown Norway rats after castration. Whereas castration caused tissue weights of all four prostatic lobes to decrease over the course of 10 days, this occurred more rapidly and to a greater magnitude in the ventral than in the dorsal, lateral, and anterior lobes. Tissue DNA content, a measure of cell number, decreased only in the ventral lobe after castration. DNA fragmentation, indicative of apoptotic cell death, was detected by in situ labeling using the terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling method and as intranucleosomal cleavage of genomic DNA analyzed by agarose gel electrophoresis. Both methods demonstrated the correlation between loss of DNA content and apoptotic cell death in the ventral lobe, whereas only the highly sensitive terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) method revealed relatively few dying cells in the dorsal, lateral, and anterior lobes after castration. Moreover, when examined as a function of age, less cell death occurred in all four lobes of old rats compared with young rats. In both young and old rat prostates, cell death was observed in epithelial and stromal cells within the ventral lobe where apoptotic cells were detected throughout the branched ductal network and were not restricted to a particular region. Taken together, these studies demonstrate the marked differences in cell death and survival between the different rat prostatic lobes in response to castration and further suggest that the androgen-sensitive apoptotic response is age dependent. Hence, the lower rates of cell death observed for the dorsal and lateral lobes, accompanied by the further decline that occurs with increasing age, are important components of the age-dependent and lobe-specific overgrowth observed for these lobes. Moreover, the age-dependent decline in apoptotic cell death observed in the prostates of old rats suggests that prostatic cells develop androgen independence as a function of age, and survival of these cells does not require androgen.

Edge enhancement and edge-enhanced correlation with photorefractive polymers.

We demonstrate a simple all-optical realization of programmable edge enhancement and edge-enhanced correlation using novel photorefractive polymers. We show that the higher non-Bragg order in a two-beam coupling scheme contains the edge enhancement of the object when placed in the path of one of the incident beams. Also, this arrangement provides a scheme for writing joint transform correlation dynamic holograms, which can be read by a third beam. The correlation is edge enhanced, and the correlation peak increases with the applied bias voltage. Numerical results without and with beam fanning are presented. Theoretical predictions are reconciled with experimental results.

A thyrotropin-like molecule from the pituitary of an Indian freshwater murrel: comparison of its biological activity with other thyrotropins.

Murrel pituitary thyrotropin-like molecule (mTSH) was purified to homogeneity with the help of a convenient and sensitive in vitro assay system where addition of this material to the thyroid follicle incubation stimulated thyroxine (T(4)) secretion into the medium. Pituitary extract of a freshwater murrel, Channa punctatus, was solvent extracted to obtain glycoprotein enriched fraction. This was subjected to Sephadex G-100 gel filtration and eluate of void volume (peak I) showed strong TSH activity (as reflected from T(4) secretion) which was further purified by using concanavalin A-Sepharose, FPLC Mono Q and immunoaffinity chromatography. Purified mTSH gave a single band in PAGE, and SDS PAGE revealed two dissimilar subunits, alpha and beta. Addition of increasing concentrations of mTSH, Indian carp TSH (cTSH) and bovine TSH (bTSH) to in vitro murrel thyroid follicle incubations caused a linear increase in thyroxine (T(4)) release into the medium, effect was highest with mTSH and lowest with bTSH. However, in in vivo experiments, injections of increasing doses of mTSH to murrel elevated plasma T(4) level in a linear manner while bTSH gave a biphasic response. Addition of mTSH and bTSH to rat or goat thyroid epithelial cell incubations equally stimulated T(4) release into the medium, while cTSH had significantly less effect. Binding affinity (K(a)) and receptor occupancy (B(max)) of mTSH to murrel thyroid follicular membrane preparation was considerably higher in comparison to cTSH or bTSH whereas both mTSH and bTSH had nearly similar K(a) and B(max) with rat thyroid epithelial cell membrane preparation. Findings indicate that mTSH is a more potent TSH as compared to carp and bovine TSH in murrel and has equipotent biological activity as bTSH on rat and goat thyroid.

Germ cell apoptosis in the testes of Sprague Dawley rats following testosterone withdrawal by ethane 1,2-dimethanesulfonate administration: relationship to Fas?

Germ cell apoptosis, which occurs normally during spermatogenesis, increases after testosterone withdrawal from the testis. The molecular mechanism by which this occurs remains uncertain. The Fas system has been implicated as a possible key regulator of apoptosis in various cells: binding of Fas ligand (FasL), a type II transmembrane protein, to Fas, a type I transmembrane receptor protein, triggers apoptosis in cells expressing Fas. Recently, Fas has been localized to germ cells, and FasL to Sertoli cells, within the rat testis. We hypothesized that Fas protein content would rise in response to reduced levels of testosterone as part of a suicide pathway that would result in germ cell apoptosis. To test this hypothesis, ethane 1,2-dimethanesulfonate (EDS), a Leydig cell toxicant, was used to kill Leydig cells and thus reduce intratesticular testosterone levels in Sprague Dawley rats. Apoptosis was examined in situ and biochemically, and Fas protein content in the testis was monitored by Western blot analysis. We show that EDS injection results in the following sequence of events: apoptotic death of Leydig cells by a mechanism that does not involve Fas; reduced testosterone; increased testicular Fas content; and germ cell apoptosis. These results suggest that Fas may play a role in the apoptotic death of germ cells that results from reduced intratesticular testosterone levels, and that testosterone may play a role in germ cell survival via its suppression of Fas.

Multiwave coupling in a high-gain photorefractive polymer.

The characteristics of a new high-gain photorefractive polymer composite with a PNP chromophore are investigated. Competition between beam fanning and two-wave coupling (TWC) is predicted and verified experimentally. The intensity dependence of TWC gain is studied. Higher diffraction order and forward phase conjugation in a TWC geometry are observed and explained.

Age-dependent and lobe-specific spontaneous hyperplasia in the brown Norway rat prostate.

We showed previously that exogenously administered testosterone caused age- and lobe-specific overgrowth of the prostate in Brown Norway rats. A common feature observed in testosterone-treated animals was cell hypertrophy in each of the ventral, dorsal, and lateral lobes of both young (6 mo old) and old (24 mo old) rats. By contrast, hyperplasia was seen only in the dorsal and lateral lobes of old rats treated with testosterone. These observations prompted us to examine whether age- and lobe-specific overgrowth might also occur in untreated rats as a consequence of the endogenous hormonal milieu. To this end, blood and prostates were collected from a large number (25-30 rats per group) of 4- to 6-mo-old (young) and 21- to 24-mo-old (old) Brown Norway rats. Both serum testosterone (-45%) and estradiol (-22%) concentrations decreased significantly with age, but the greater magnitude of the decrement in testosterone relative to estradiol led to a reduction in the serum testosterone:estradiol ratio. Paradoxically, although the prostate is androgen dependent, the wet weight, protein, and DNA contents increased significantly with age in the dorsal and lateral lobes of old rats despite the decrease in testosterone level. Histologic examination revealed that the increased weights and DNA contents of the dorsal and lateral lobes in old rats coincided with an increased number of epithelial cells in the distal and intermediate segments of these lobes, indicative of hyperplasia but independent of change in cell size. Taken together, these results show a spontaneous age-related overgrowth of cells in the dorsal and lateral prostatic lobes of old Brown Norway rats despite diminished serum testosterone concentrations. The aging Brown Norway rat, therefore, may be a useful model for studies of some aspects of the pathogenesis underlying spontaneous age-related prostatic hyperplasia.

Regional expression of transforming growth factor-alpha in rat ventral prostate during postnatal development, after androgen ablation, and after androgen replacement.

The prostate is a highly heterogeneous organ, composed of different types of epithelial and stromal cells organized regionally along the ductal network. Although androgen-stimulated growth and maintenance of the prostate gland primarily involve epithelial cells, it is unclear whether all epithelial cells are androgen dependent. Moreover, the actions of androgens may not be direct; a number of polypeptide growth factors, including transforming growth factor-alpha (TGFalpha), are postulated to mediate androgen action in the rat prostate. In this investigation, using an immunohistochemical technique, we examined the cellular and regional expression of TGFalpha in the rat ventral prostate during postnatal development to adulthood. TGFalpha-immunopositive cells were located throughout the ductal epithelium from postnatal days 5-20. By day 45 and thereafter, regional variation in TGFalpha expression became apparent; epithelial cells in the proximal segment exhibited intense staining, whereas those in the distal segment exhibited negligible staining. These observations were coincident with increased serum testosterone concentrations at puberty. To understand the role of androgen in the expression of TGFalpha in the epithelial cells of the distal and proximal segments of the adult rat ventral prostate, androgen was withdrawn by castration, and testosterone subsequently was administered. Androgen receptor protein expression decreased after castration and reappeared after androgen replacement in both the distal and proximal segments. TGFalpha staining was negligible in epithelial cells of the distal segment of intact adult rats, became prominent by 7 days after castration, but then diminished after the administration of testosterone. Western blot analyses revealed the presence of a specific 30-kDa immunoreactive form of TGFalpha in rat ventral prostate, and its quantity reflected the staining intensities observed in the immunohistochemical studies. These results suggest that TGFalpha expression is negatively regulated by androgen in epithelial cells of the distal segment. In contrast, staining for TGFalpha in epithelial cells of the proximal segment did not change with castration or testosterone administration, suggesting that TGFalpha is not regulated by androgen in this region of the ventral prostate. In summary, TGFalpha expression is differentially regulated among epithelial cells localized in two different regions of the ventral prostate. We hypothesize that TGFalpha may function as a survival factor for epithelial cells which, as a consequence of its expression, become androgen independent and thus escape apoptotic cell death after androgen ablation.

Serology and immunoglobulin profile in rheumatoid arthritis.

One hundred and twenty cases of clinically diagnosed rheumatoid arthritis, 80 non-rheumatoid cases suffering from various other diseases and 40 healthy individuals were investigated for the presence of rheumatoid factor, quantitation of serum immunoglobulin, demonstration of ANA and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid factor showed 56.6% positivity in rheumatoid group and 3.7% positivity in non-rheumatoid group. All three serum immunoglobulins (IgG, IgM, IgA) were raised in serum in significant titre in cases of rheumatoid arthritis, whereas only IgA lever was elevated in the group of non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 11.7% and 4.4% cases of rheumatoid arthritis who had severe underlying disease. In non-rheumatoid group, only one of 6 cases of systemic lupus erythematosus showed rheumatoid factor and that too in an insignificant titre (less than 1:20). Synovium and synovial fluid contained plenty of plasma cells and lymphocytes. It has been observed that RF appears first in synovial fluid and it may take several months to a year to attain detectable level in serum.

Telomerase activity in normal adult Brown Norway rat seminal vesicle: regional distribution and age-dependent changes.

Telomerase activity is essential for protection of cells against the telomere erosion that occurs with each round of cell replication, and thus appears to play a role in the indefinite replication potential of some, but not all, eukaryotic cells. In this regard, some tissues contain stem cells that have a long proliferative life-span and are capable of regenerating or renewing the somatic epithelial cell population within the tissue. Because the adult seminal vesicle exhibits the ability to regenerate during androgen-replacement after castration, we hypothesized that a pool of cells with regenerating potential is present in the adult seminal vesicle, which expresses telomerase activity. In this study, we used a highly sensitive PCR-based telomerase assay [the telomeric repeat amplification protocol (TRAP) assay] to detect telomerase activity in rat seminal vesicle. Our results show that telomerase activity is, indeed, present in the normal adult rat seminal vesicle, but that, in the presence of seminal vesicle fluid, telomerase activity cannot be detected. In fact, seminal vesicle fluid was found to contain some factor(s) that is inhibitory for the TRAP assay. In addition, we found that telomerase activity in the seminal vesicle changes with age and is regionally distributed within the distal, intermediate, and proximal segments of the duct. These results suggest that as is the case for the rat prostate, a population of telomerase-positive cells is present within the adult rat seminal vesicle, and thereby, this organ retains throughout life the potential to regenerate in response to androgen replacement following castration-induced apoptotic cell death.