Influence of atmospheric factors on the rheumatic diseases

There appears to be ample evidence to conclude that various meteorological factors do exert a significant impact on some people with various rheumatic diseases. The data is, however, crude relative to our general understanding. Most of this research on RA has dealt with the primary signs and symptoms of inflammation. We know, however, many of the chemical mediators of inflammation. It seems like a logical progression of research to determine the effects of the meteorological/atmospheric factors of concern on these specific intrinsic mediators of inflammation. In general, gout can be very well controlled through medication. The evidence suggests, however, that we may gain a much better understanding of how atmospheric factors such as temperature can effect the body through changes in its physico-chemical processes by using Gout as a model. The work with SLE has already yielded useful applications. Sun screening pharmaceuticals have been quite successful in reducing exacerbations of symptoms. But we don't know why only some people are photosensitive. The previous research on the effects of atmospheric factors on the rheumatic diseases has illustrated key issues in methodology: large sample sizes are critical, objective and quantifiable disease variables are important, the variables measured must be specific to the questions investigated, the diseases investigated must be as specifically and accurately defined as possible, and the various aspects of 'weather' to be investigated must be specifically defined and quantified. It is apparent that there is much more important and useful work to be performed before we can understand the effects of atmospheric factors on the rheumatic diseases.     

Central neural control of pineal melatonin synthesis in the rat

To investigate a possible central neural influence on nocturnal pineal metabolic activity in rats, frontal transsections of the stria medullaris thalami were conducted. Enzymes involved in melatonin synthesis, i.e. N-acetyltransferase and hydroxyindole-O-methyl-transferase, exhibited reduced activities in operated animals when compared to controls. These results indicate a modulatory role of central structures on nocturnal pineal indole metabolism.     

3-Amino-3-deoxy-D-glucose: an antibiotic produced by a deep-sea bacterium

Gram-positive bacteria isolated from deep-sea sediments of the Pacific basin showed considerable antibacterial activity. A Bacillus strain, isolated from a sediment sample collected at a depth of 4310 m, was shown to produce 3-amino-3-deoxy-D-glucose, a known antibiotic.     

Uptake and toxic effects of heavy metal ions: interactions among cadmium, copper and zinc in cultured cells

Absorption of metal ions by KB, HeLa and L-59 cells has been analyzed by atomic absorption spectrophotometry in the course of culture. Ions of the elements of the fourth period in the periodic chart such as Fe(II), Cu(II), Zn(II), Mn(II) and Ni(II) were not taken up, but those of the higher periods, such as Cd(II), Pb(II), Hg(II) and Ag(I) were were taken up easily. The uptake behavior by the cultured cells was in accordance with the characteristic features of metals, that metals in the fourth period are essential elements, and most of the elements of the fifth and the sixth periods are non-essential or toxic elements. The initial rate of Cd(II) uptake and the Cd(II) concentration has a sigmoidal relationship. Cd(II) was absorbed homotropically through cell membranes. The uptake of Cd(II) was specifically inhibited by Cu(II), but was affected little by Zn(II). The toxicity of Cd(II) to KB cells was greatly enhanced in the presence of Cu(II). On the contrary, the toxicity of Cd(II) was reduced by the addition of Zn(II) at several concentrations of Cd(II). The toxicity of Cd(II) did not depend on the amount of Cd(II) absorbed in the cells, but was determined by cofactors such as Cu(II). The interaction between Cd(II) and Cu(II) may be important for Itai-itai disease.     

Effect of oridonin, a Rabdosia diterpenoid, on radiosensitization with misonidazole

The radiosensitization brought about by oridonin, one of the Rabdosia diterpenoids, alone or in combination with misonidazole, was investigated in Chinese hamster V79 cells. The enhancement ratio of 1.92 was obtained when 0.01 mM oridonin and 1 mM misonidazole were administered to hypoxic cells under radiation. The enhancement ratios of oridonin and misonidazole for hypoxic cells were 1.16 and 1.59 respectively. Hence, a supra-additive effect was obtained by the combined treatment with these two drugs. Under aerobic conditions, no effect of 0.01 mM oridonin on the radiosensitization caused by misonidazole was observed.     

Evidence for an olfactory receptor which responds to nicotine--nicotine as an odorant

The tobacco alkaloid (S)(-)-nicotine, when applied as a vapour to an in vitro head preparation, stimulates the olfactory epithelium in three strains of rats and to a lesser extent in two strains of mice. The electro-olfactogram (EOG) generated by nicotine has similar characteristics to the EOGs produced by known odorants. The nicotine EOG increases with increasing concentration of nicotine vapour (1-100 nM) applied to the olfactory epithelium. Differential reduction of the nicotine EOG by the lectin concanavalin A is seen in Wistar and Lister Hooded rats. The reduction of the nicotine EOG by concanavalin A is prevented by adding alpha-methyl-D-mannoside to the lectin superfusion medium. This suggests that there is a glyco-moiety associated with at least one olfactory receptor responding to nicotine. Our results suggest that rat olfactory epithelium has receptor sites for nicotine. Nicotine is an unusual compound because it shows both odorant and pharmacological properties.     

Increased responsiveness of the hypothalamic-pituitary axis to steroid feedback effects in ovariectomized rats treated neonatally with monosodium L-glutamate

Chronic ovariectomized rats treated neonatally with MSG showed reduced circulating concentrations of LH coupled with elevated hypothalamic LHRH stores. Despite the apparent loss of LHRH secretion, the small pituitary glands showed an increased density of LHRH receptors and normal responsiveness to the releasing hormone. The positive feedback effects of progesterone on LH release in oestrogen-primed animals was greatly exaggerated reflecting the build-up of hypothalamic LHRH stores without loss of pituitary responsiveness to LHRH.     

CD1d and natural T cells: how their properties jump-start the immune system

Cellular and humoral immune mechanisms recruited to defend the host from infectious agents depend upon the early immune events triggered by antigen. The cytokine milieu within which the immune response matures is the most important of many factors that govern the nature of the immune response. Natural T cells, whose function is controlled by CD1d molecules, are an early source of cytokines that can bestow type 1 or type 2 differentiative potential upon helper T lymphocytes. This review attempts to illuminate the glycolipid antigen presentation properties of CD1d, how CD1d controls the function of natural T cells and how CD1d and natural T cells interact to jump start the immune system. CD1d is postulated to function as a sensor, sensing alterations in cellular lipid content by virtue of its affinity for such ligands. The presentation of a neo-self glycolipid, presumably by infectious assault of antigen-presenting cells, activates natural T cells, which promptly release pro-inflammatory and anti-inflammatory cytokines and jumpstart the immune system. Received 10 July 2000; received after revision 16 October 2000, accepted 16 November 2000     

Binding of estradiol to synaptosomal mitochondria: physiological significance

The subsynaptosomal distribution and specific binding of 17beta-estradiol in vitro to mitochondria isolated from presynaptic nerve endings of female rat brain were examined. 17Beta-estradiol is (i) distributed unequally in synaptosomes and mitochondria posses the highest capacity to bind estradiol with respect to the available amount of the hormone. (ii) Estradiol binds specifically to isolated synaptosomal mitochondria. A Michaelis-Menten plot of specific binding was sigmoidal within a concentration range of 0.1-5 nM of added estradiol, with a saturation plateau at 3 nM. Binding of higher estradiol concentrations demonstrated an exponential Michaelis-Menten plot, indicating non-specific binding to mitochondria. Vmax and Km for the sigmoidal-shape range were estimated as 46 +/- 6 fmol of estradiol/mg of mitochondrial proteins and 0.46 +/- 0.07 nM free estradiol respectively. (iii) Estradiol binding is not affected by the removal of ovaries. The results show that inhibition of Na-dependent Ca2+ efflux from mitochondria by estradiol occurs according to an affinity change of the translocator for Na+, at the same estradiol concentrations that show specific binding to mitochondrial membranes. These data imply that physiological concentrations of estradiol, acting on mitochondrial membrane properties, extragenomically modulate the mitochondrial, and consequently the synaptosomal content of Ca2+, and in that way exert a significant change in nerve cell homeostasis.     

Transformation: a tool for studying fungal pathogens of plants

Plant diseases caused by plant pathogenic fungi continuously threaten the sustainability of global crop production. An effective way to study the disease-causing mechanisms of these organisms is to disrupt their genes, in both a targeted and random manner, so as to isolate mutants exhibiting altered virulence. Although a number of techniques have been employed for such an analysis, those based on transformation are by far the most commonly used. In filamentous fungi, the introduction of DNA by transformation typically results in either the heterologous (illegitimate) integration or the homologous integration of the transforming DNA into the target genome. Homologous integration permits a targeted gene disruption by replacing the wild-type allele on the genome with a mutant allele on transforming DNA. This process has been widely used to determine the role of newly isolated fungal genes in pathogenicity. The heterologous integration of transforming DNA causes a random process of gene disruption (insertional mutagenesis) and has led to the isolation of many fungal mutants defective in pathogenicity. A big advantage of insertional mutagenesis over the more traditional chemical or radiation mutagenesis procedures is that the mutated gene is tagged by transforming DNA and can subsequently be cloned using the transforming DNA. The application of various transformation-based techniques for fungal gene manipulation and how they have increased our understanding and appreciation of some of the most serious plant pathogenic fungi are discussed. Received 9 May 2001; received after revision 2 July 2001; accepted 3 July 2001