DIETARY HISTIDINE INCREASES MOUSE SKIN UROCANIC ACID LEVELS AND ENHANCES UVB-INDUCED IMMUNE SUPPRESSION OF CONTACT HYPERSNSITIVITY

Urocanic Acid (UCA) exists in mammalian skin primarily as the trans isomer and is photoisomerized to cis UCA upon UVB absorption. Our previous studies indicated that the photoisomerization of UCA is the initiating event in UBV-induced suppression of cell-mediated immunity (tUCA----cUCA----immune suppression). The purpose of this study was to verify the role of UCA in UV-induced immune suppression of contact hypersensitivity (CHS) in BALB/c mice. Since UCA is a metabolite of the amino acid L-histidine, we reasoned that increased dietary levels of histidine should raise skin tUCA levels. If skin tUCA is the UVB photoreceptor for immune suppression, this increase should enhance UV-induced suppression of CHS. HPLC analysis of skin from BALB/c mice given a histidine-rich diet (10%) showed that the total amount of UCA is significantly higher in these animals than in mice fed a normal diet. Further, levels of suppression of CHS of 3% and 49% in control fed mice, induced by 4.8 and 7.2 kJ/m2 UVB were significantly increased to 21% and 71% respectively in histidine-fed animals at these same UVB doses. These findings provide additional support for the UCA model for immune suppression, and provide the first evidence that UV-induced immune suppression can be enhanced by a dietary component, L-histidine.     

UVB-INDUCED SUPPRESSION OF THE MIXED EPIDERMAL CELL LYMPHOCYTE REACTION IS CRITICALLY DEPENDENT ON IRRADIANCE

The mixed epidermal cell lymphocyte reaction (MECLR) is a commonly used method to study the effects of ultraviolet B (UVB) radiation on the skin immune system. In UVB experiments dosimetry is very important. The influence of irradiance on the MECLR was studied in vitro using Philips FS40 lamps with variable UV intensities. Irradiation of isolated epidermal cells with high irradiance impaired the alloactivating capacity more than irradiation with low irradiance. In vivo, the influence of long-term UVB exposure on the MECLR was studied by treating normal healthy volunteers with suberythemagenic doses of UVB thrice weekly during 4 weeks. The first set of experiments, using low irradiance Sylvania UV-21 F75/85 W lamps, resulted in a decrease of MECLR responses of 83.1%. In the second set of experiments performed a year later, employing an identical protocol except for the use of high irradiance Waldmann UV-21 F85/100 W lamps, an increase of MECLR responses of 99.7% was observed. Volunteers of both sets of experiments received equal doses of UVB. In conclusion, this study shows that in vitro UVB-induced suppression of the MECLR is critically dependent on irradiance and therefore might explain contradictory results described in the literature. The in vivo data suggest that, comparable to the in vitro experiments, irradiance may influence the effects of UVB irradiation in vivo. Further experiments should prove whether this is indeed the case.     

BIOLOGICALLY EFFECTIVE DOSES OF SUNLIGHT FOR IMMUNE SUPPRESSION AT VARIOUS LATITUDES AND THEIR RELATIONSHIP TO CHANGES IN STRATOSPHERIC OZONE

Using information on solar irradiance at different latitudes derived from a radiative transfer model and a detailed in vivo action spectrum for immune suppression in a murine system, we report here calculations of the "biologically effective" irradiance of sunlight for immune suppression. From 40 degrees N to 40 degrees S in summer, under normal stratospheric ozone concentrations this value ranged from 0.27 W/m2 (40 degrees N or S) to a peak of 0.33 W/m2 (20 degrees N or S) predicting that 50% immune suppression in the Balb/c mouse would occur after 21-26 min of sunlight exposure within this latitude range. We also found that the most effective wavelengths for immune suppression shift from a peak of 270 nm in the laboratory to near 315 nm in sunlight. Furthermore, using ozone depletion scenarios of 5 to 20%, at latitudes 20 degrees S and 40 degrees N, a 0.6% increase in biologically effective irradiance levels of solar UVB for immune suppression was predicted for each 1% decrease of ozone. This value rose to a nearly 1% increase for each 1% decrease in ozone at 60 degrees N latitude in wintertime. These data indicate that activation of immune suppression, in a murine model, requires relatively low levels of sunlight and that these levels are easily obtainable over most of the populated regions of the world. Since a UVB-activated photoreceptor, urocanic acid, regulates immune suppression in mice and since this same compound exists on other mammalian skin, including human skin, suppression of the mammalian immune system is predicted to increase if substantial stratospheric ozone depletion takes place.     

SUPPRESSION OF CONTACT HYPERSENSITIVITY BY UV RADIATION AND ITS RELATIONSHIP TO UV-INDUCED SUPPRESSION OF TUMOR IMMUNITY

Abstract— In this study, we examine some of the photobiologic and immunologic characteristics of the suppression of contact hypersensitivity (CHS) by UV radiation. BALB/c mice were irradiated on the shaved dorsal skin with FS40 sunlamps and sensitized 5 days later by applying a contact sensitizer lo the shaved abdomen. The suppression of CHS resulting from exposure to a given total dose of UV radiation was unaffected by changes in dose fractionation over a 5-day period and by changes in dose-rate over a 10-fold range. Elimination of wavelengths below 315 nm with a mylar filter abrogated the suppressive effect of the sunlamps, even when the same total energy was administered. Irradiation of unshaved mice required 14 times more energy to produce 50% suppression than was required for shaved mice, suggesting that the exposed skin is the primary target of this effect. Contact sensitization of UV-irradiated, but not unirradiated, mice induced the appearance of antigen-specific suppressor T lymphocytes in their spleen. The photobiologic and immunologic similarities between the suppression of CHS by UV radiation and the UV-mediated suppression of tumor rejection that we described previously suggest that these two immunosuppressive effects of UV exposure share certain steps in their pathways.     

PSORALEN AND THE SUPPRESSION OF MELATONIN SECRETION BY BRIGHT LIGHT

Abstract— Melatonin plasma levels were analyzed in 21 normal human subjects placed in darkness frm 7:30 p.m. to 11 p.m. and then submitted to bright light exposure (over 1500 lx) to 2 a.m. 5-Methoxypsoralen (5-MOP) was orally (40 mg) given to 11 of those subjects at 9 p.m. In darkness, melatonin plasma levels increased slightly in untreated subjects and dramatically in subjects having received 5-MOP. Under bright light exposure, the melatonin plasma levels were significantly reduced in drug free controls but not in treated subjects.     

SUPPRESSION OF PHAGE T4 BY CO-INFECTION WITH U.V.-INACTIVATED HOMOLOGOUS PHAGE

Abstract— Unirradiated phage T4v₁ may fail to produce viable progeny in cells which are co-infected with u.v.-irradiated homologous particles. The extent of this effect, called suppression , is positively correlated with the multiplicity of infection of the irradiated phage and with the U.V. dose. The suppression reaches a maximum level at about 30–600 lethal hits. Quantitative evaluation of the results shows that in some complexes one irradiated phage particle is sufficient to suppress an unirradiated phage. Two hypotheses are discussed to explain the results. (a) Lethal u.v.-damages are incorporated into the unirradiated phage genome by genetic recombination; ( b ) Genetic subunits (e.g. cistrons or operons) of the u.v.-irradiated phages produce informationally incorrect messenger RNA molecules, which compete with the correct ones from the unirradiated phage in the protein-synthetizing system. Hypothesis (6) appears to be more adequate to explain the experimental results.     

SUPPRESSION OF LIPID PHOTOPEROXIDATION BY QUERCETIN AND ITS GLYCOSIDES IN SPINACH CHLOROPLASTS

Abstract— Quercetin, quercitrin and rutin suppressed lipid photoperoxidation in spinach chloroplasts in the presence of 100 μ M carbonylcyanide m -chlorophenylhydrazone (CCCP) or 100 μ M methyl viologen (MV). Fifty percent inhibition of lipid peroxidation by quercetin was observed between 30 and 50 μ M . Concentrations of quercetin and rutin higher than 100 μ M were required to obtain 50% inhibition. Ouercitrin was more effective than rutin in the suppression of lipid photoperoxidation.
Photooxidation of the flavonols by chloroplasts in the presence of MV was suppressed by superoxide dismutase (SOD) more than 90%, and the rates of the oxidation decreased in order of quercetin, quer citrin and rutin suggesting that the reactivity of the flavonols with O₂-decreased in that order. The photooxidation of the flavonols by CCCP-poisoned chloroplasts was partially suppressed by SOD. Radicals generated in the course of lauroyl peroxide degradation also oxidized the flavonols and the oxidation was insensitive to SOD. In these experiments, oxidation rate of quercetin was faster than those of its glycosides. The results obtained suggest that flavonols can function as antioxidants in chloroplasts by scavenging both O₂-and the radicals formed during lipid peroxidation.     

TANNING SALON EXPOSURE SUPPRESSION OF DNA REPAIR CAPACITY AND MITOGEN-INDUCED DNA SYNTHESIS

Mitogen responsiveness and the capacity to repair genetic damage were measured in lymphocytes collected from young, healthy, adult Caucasians immediately before exposure in commercial tanning salons and again 24 h after exposure. For every individual studied, tanning exposure produced significant inhibition of phytohemagglutinin-induced mitogenesis or of the ability to repair DNA lesions by unscheduled DNA synthesis. The results imply that such exposure could: (1) pose a significant hazard for individuals who are already immunosuppressed (e.g. cancer patients, AIDS patients or carriers of latent HIV) and (2) increase the carcinogenic effects of environmental mutagens.     

EFFECT OF UV IRRADIATION ON LETHAL INFECTION OF MICE WITH Candida albicans

Exposure of mice to UV radiation inhibits the induction and elicitation of the delayed-type hypersensitivity (DTH) response to Candida albicans. To determine whether UV irradiation also affects the pathogenesis of systemic C. albicans infection, C3H mice were exposed to a single dose of 48 kJ/m² UV-B radiation from FS40 sunlamps 5 days before or 5 days after sensitization with formalin-fixed C. albicans and challenged intravenously (i.v.) with a lethal dose of viable fungi 6 days after sensitization (11 or 1 days after UV irradiation). Exposing unsensitized mice to UV radiation 11 days before lethal challenge had no effect on survival, but the survival time of mice exposed to UV radiation 1 day before challenge was reduced by more than 50%. In the latter group, decreased survival time correlated with persistence of C. albicans in the brain and progressive growth of C. albicans in the kidneys. Sensitization of unirradiated mice with formalin-fixed C. albicans extended their survival time following lethal i.v. challenge with viable C. albicans. Exposing the mice to UV radiation 5 days before sensitization did not abrogate this beneficial effect of sensitization on survival, even though it significantly reduced the DTH response. Thus, immunity to systemic infection did not depend on the ability of the mice to exhibit a DTH response to C. albicans. The beneficial effect of sensitization on survival after lethal infection was abrogated, however, in mice exposed to UV radiation 1 day before lethal challenge with C. albicans. Furthermore, these mice were unable to contain the progressive growth of C. albicuns in the kidneys, in contrast to sensitized, unirradiated mice. The induction of cutaneous inflammation with turpentine had no effect on the survival rate of mice lethally infected with C. albicans, suggesting that inflammation alone is not sufficient to decrease the survival time of C. albicans-infected mice.     

Cis-UROCANIC ACID SYNERGIZES WITH HISTAMINE FOR INCREASED PGE2 PRODUCTION BY HUMAN KERATINOCYTES: LINK TO INDOMETHACIN-INHIBITABLE UVB-INDUCED IMMUNOSUPPRESSION

Abstract— There is considerable evidence that suppression of the immune system by UVB (280–320 nm UV) irradiation is initiated by UVB-dependent isomerization of a specific skin photoreceptor, urocanic acid (UCA), from the trans to the cis form. Previous studies have confirmed that cis -UCA administration to mice 3–5 days prior to hapten sensitization at a distant site, suppresses the contact hypersensitivity (CHS) response upon challenge. This study demonstrates in mice that cis -UCA, like UVB, suppresses CHS to trinitrochlorobenzene by a mechanism partly dependent on prostanoid production. In vitro experimentation showed that human keratinocytes, isolated from neonatal foreskin, increased prostaglandin E₂ (PGE₂) production in response to histamine but not UCA alone. However, cis -UCA synergized with histamine for increased PGE₂ production by keratinocytes. cis -urocanic acid also increased the sensitivity of keratinocytes for PGE₂ production in response to histamine. Prostaglandin E₂ from keratinocytes exposed to cis -UCA and histamine may contribute directly, or indirectly, to the regulation of CHS responses by UVB irradiation.     

PREVENTION OF UV IRRADIATION INDUCED SUPPRESSION OF MONOCYTE FUNCTIONS BY RETINOIDS AND CAROTENOIDS in vitro

Abstract— The effects of stimulation of human peripheral blood monocytes in vitro with retinoids and carotenoids, and subsequent exposure to ultraviolet light of the B wavelength were measured. The compounds were applied to the monocytes in culture for 24 h, and the washed cells were then exposed to UVB light up to 220 J/m². The compounds tested protected the monocyte from UVB induced damage to phagocytic activity. This protection may be due to the antioxidant or UVB energy-quenching properties of these compounds. Monocyte cytotoxicity against a melanoma cell line was stimulated by exposure to the retinoids or carotenoids, but a protective effect in vitro against UVB damage was not seen for this cell function.     

UROCANIC ACID ANALOGUES AND THE SUPPRESSION OF THE DELAYED TYPE HYPERSENSITIVITY RESPONSE TO Herpes simplex VIRUS

Ultraviolet irradiated urocanic acid (4-imidazoleacrylic acid) containing a mixture of cis- and trans-isomers has been shown previously to induce suppression of the delayed type hypersensitivity (DTH) response to Herpes simplex virus type 1 (HSV-1) in a murine model of infection. The cis-isomer of urocanic acid was prepared and the cis- and trans-isomers of 2-methylurocanic acid. 2-pyrroleacrylic acid, 2-furanacrylic acid, 2-thiopheneacrylic acid, 3-thiopheneacrylic acid as well as dihydrourocanic acid and histamine. Each was applied at concentrations of 1 and 50 micrograms per mouse to the shaved dorsal skin and the mice were infected subcutaneously with HSV 5 h later. After 8-10 days the DTH response to the virus was measured by an ear swelling test. It was found that cis-urocanic acid was effective in suppressing the DTH response at levels of 1 microgram per mouse or less. The cis- and trans-isomers of 2-furanacrylic acid, 2-pyrroleacrylic acid and 2-thiopheneacrylic acid were also effective, with the cis- form generally being more active than trans, and 2-pyrroleacrylic acid being particularly potent. Cis- and trans-3-thiopheneacrylic acid, on the other hand, were only marginally immunosuppressive while neither isomer of 2-methylurocanic acid had any suppressive ability. Dihydrourocanic acid and histamine were also shown to suppress the DTH response. Thus the structural features necessary for urocanic acid and its analogues to act as mediators of UV-induced immunosuppression could be deduced and implications for their mechanism of action discussed.     

DIFFRACTION AND HOLOGRAPHY WITH PHOTOELECTRONS AND FLUORESCENT X-RAYS

We consider studies of the atomic and magnetic structure near surfaces by photoelectron diffraction and by the holographic inversion of both photoelectron diffraction data and diffraction data involving the emission of fluorescent x-rays. The current status of photoelectron diffraction studies of surfaces, interfaces, and other nanostructures is first briefly reviewed, and then several recent developments and proposals for future areas of application are discussed. The application of full-solid-angle diffraction data, together with simultaneous characterization by low energy electron diffraction and scanning tunneling microscopy, to the epitaxial growth of oxides and metals is considered. Several new avenues that are being opened up by third-generation synchrotron radiation sources are also discussed. These include site-resolved photoelectron diffraction from surface and interface atoms, the possibility of time-resolved measurements of surface reactions with chemical-state resolution, and circular dichroism in photoelectron angular distributions from both non-magnetic and magnetic systems. The addition of spin to the photoelectron diffraction measurement is also considered as a method for studying short-range magnetic order, including the measurement of surface magnetic phase transitions. This spin sensitivity can be achieved through either core-level multiplet splittings or circular-polarized excitation of spin-orbit-split levels. The direct imaging of short-range atomic structure by both photoelectron holography and two distinct types of x-ray holography involving fluorescent emission is also discussed. Both photoelectron and x-ray holography have demonstrated the ability to directly determine at least approximate atomic structures in three dimensions. Photoelectron holography with spin resolution may make it possible also to study short-range magnetic order in a holographic fashion. Although much more recent in its first experimental demonstrations, x-ray fluorescence holography should permit deriving more accurate atomic images for a variety of materials, including both surface and bulk regions.     

PHOTOSENSITIZATION WITH ETIOBENZOCHLORINS AND OCTAETHYLBENZOCHLORINS

The photophysical and photobiological properties of a series of etiobenzochlorins were evaluated in cell culture using murine leukemia L1210 cells. In the series of agents tested, the chlorin-(mono)sulfonate was the most efficacious, the tin chlorin somewhat less so and the tin chlorin-sulfonate much less active. The parent chlorin was essentially inactive at the limit of solubility. Photodamage was assessed by measuring alterations in surface hydro-phobicity ( via a two-phase partitioning procedure), amino acid transport and membrane potential. Additional information was provided from fluorescence microscopy, which was used to identify sites of sensitizer binding and effects of photodamage on the binding patterns of fluorescent probes specific for mitochondria, lysosomes and plasma membranes. Effects of photodamage on fluorescence lifetime distribution of the membrane probe trimethylamino-diphenyl hexatriene were examined. The data obtained were consistent with localization of the parent etiobenzochlorin and tin derivative at lysosomal loci. the chlorin-sulfonate at plasma and mitochondrial membranes and tin-sulfonate at the cell surface.     

TIN AND GERMANIUM COMPLEXES WITH MALTOL

Abstract

The reaction of tin and germanium tetrachlorides with 3-hydroxy-2-methyl-4H-pyran-4-one (HMa) in benzene yielded M(HMa)₄Cl₄·C₆H₆ (M = Sn or Ge) adducts, whereas in methanol the MMa₂Cl₂ complexes have been isolated. Moreover, tin complexes with the neutral donors 2,6-dimethyl-4H-pyran-4-one (DMP) and 2,6-dimethyl-4H-pyran-4-thione (DMTP), having formulae Sn(L)₂Cl₂ and Sn(L)₂Cl₄(L = DMP or DMTP) have been prepared. The compounds have been characterized by ir and proton nmr spectroscopy and by thermogravimetric (TG and DTA) analysis. The thermal behaviour of all complexes has been followed to 1200°C. The stability of the M(HMa)₄Cl₄ adducts in various solvents is discussed on the basis of proton nmr spectra.     

热敏性高分子包裹的磁性微球的性质及表征

利用扫描电镜、红外光谱、元素分析仪、热分析及激光散射粒径分析仪等手段对合成得到的Ｆｅ３Ｏ４／Ｐ（Ｓｔ ＮＩＰＡＭ）（ＰＳＮ） 和ＰＳＮＮ 微球的形貌、结构、磁响应性和热敏特性等进行了表征,结果表明微球的粒径分布呈正态分布,共聚物微球的Ｔｇ 随ＮＩＰＡＭ 组分的增加而升高,ＰＳＮ 和ＰＳＮＮ 微球均具有较强的磁响应性,其流体动力学粒径随温度的升高而减小．     

超大孔磷酸铝分子筛的合成及性能

1988年Davis等首次报道了以二正丙胺和四丁基氢氧化铵为结构导向剂合成出一种命名为VPI-5的新型磷酸铝超大孔分子筛。它是一族具有相同三维拓朴学骨架的磷酸铝系分子筛,该结构的对称性属六方晶系,P6_3cm空间群,单位晶胞由36个TO_2组成,晶胞参数α=1.8989nm,c=0.8112nm,其主孔道由18员环构成,孔直径约为1.2-1.3nm。     

MICROEMULSIONS AND LIQUID CRYSTALS WITH WHITE OIL

Phase maps were determined in the system water, sodium dodocyl sulfate, pentanol and a commercial mineral oil (Drakeol® 7) and the dimensions in the lamellar liquid crystal were determined using low angle x-ray diffraction. The mineral oil gave a strong reduction in the water-in-oil microemulsion region solubilization capacity for water when combined with the cosurfactant in a 1/1 weight ratio. For less oil/cosurfactant ratios a large oil-in-water microemulsion region was observed

The mineral oil added to the liquid crystal in the system strongly reduced the water penetration into the hydrocarbon chain region and enhanced the disorder of the hydrocarbon chains in the structure.