The role of psychoneuroimmunology in the pathogenesis of psoriasis.

Although it is well known that stress can trigger and exacerbate psoriasis, the exact mechanism is unknown. An explanation is presented based on recent findings in psychoneuroimmunology. The number of cutaneous sensory nerves known to release neuropeptides, such as substance P, is increased in patients with psoriasis.

Protective activity of different hepatic cytosolic glutathione S-transferases against DNA-binding metabolites of aflatoxin B1.

To evaluate the role of glutathione S-transferase (GST) isoenzymes in induced resistance of hepatocytes to aflatoxin B1 (AFB1), we compared DNA protective activities of different hepatic cytosol preparations and purified GSTs from normal rats, rats exposed to different polychlorinated biphenyls (PCBs), and rats with carcinogen-induced hepatocellular neoplasms, with cytosols or purified GSTs from mouse, rainbow trout, and human livers. These comparisons were performed in an in vitro assay for [3H]AFB1-DNA binding after activation by rat liver microsomes. Cytosol and S-hexylglutathione-affinity-purified GST preparations from livers of mice consistently had strong protective activity against AFB1-DNA binding.

The role of cutaneous sensory nerves in the maintenance of psoriasis.

This is a case report of two patients with chronic plaque psoriasis in whom cutaneous nerve damage resulted in clearance of the disease at that site. In both patients reappearance of the psoriasis occurred with recovery of cutaneous sensation. The role of cutaneous sensation in the maintenance of skin disorders and, in particular, the role of neuropeptides in the pathogenesis of psoriasis are discussed.

Prevention by free radical scavenger AD5 of prooxidant effects of choline deficiency.

This study was designed to explore the possible preventive effects of a novel radicophile, N-p-methoxyphenylacetyl-dehydroalanine (AD5) and three other antioxidants, N,N'-diphenyl-p-phenylenediamine (DPPD), butylated hydroxyanisole (BHA) and a water-soluble analogue of vitamin E, trolox C, on the acute effects of the liver of feeding a choline-deficient (CD) diet. It has been suggested that some of the acute effects of a CD diet are related to free radicals, the generation or metabolism of which is disturbed in this acute dietary model. AD5 was found to be very effective in preventing nuclear lipid peroxidation, DNA damage and cell death induced by a CD diet but to have little effect on triglyceride accumulation ("fatty liver").

Protective value of a liver initiation-promotion regimen against the lethal effect of carbon tetrachloride in rats.

This study was designed as one test of the hypothesis that an early sequence of steps in hepatocarcinogenesis in the rat, with the production of hepatocyte nodules, may be a special form of adaptive response that has survival value for the host. Fischer 344 rats were initiated with a single dose of diethylnitrosamine. Hepatocyte nodules were rapidly generated by selecting for resistant hepatocytes by a brief exposure to 2-acetylaminofluorene coupled with partial hepatectomy, a procedure that leads to liver cancer without any further treatment.

In situ detection of DNA-binding proteins in herpes simplex virus type 1-infected cells.

An in situ assay for detecting DNA-binding proteins in herpes simplex virus type 1 (HSV-1)-infected cells is described. Seventeen HSV-induced DNA-binding species were visible with nicked, double-stranded DNA as a substrate, while fourteen virus-induced DNA-binding fractions were present in gels containing nuclease-treated, single-stranded DNA. The effects of HSV on cellular DNA-binding protein expression could also be seen.

Kinetics of interaction of 2-acetylaminofluorene with normal liver and carcinogen-induced hepatocyte nodules in vivo and in vitro.

This study examines the initial uptake and subcellular distribution of the carcinogen [14C]-2-acetylaminofluorene in liver nodules and normal liver. The route of administration of the carcinogen was intravenously through a peripheral branch of the superior mesenteric vein, intragastrically or intraperitoneally. Tissue distribution was initially dependent on blood flow, but the retention after 5 minutes varied between different tissues according to tissue affinity, high in liver, fat and muscle, low in kidney and brain.

Kinetics of excretion of 2-acetylaminofluorene in normal and xenobiotic-treated rats and in rats with hepatocyte nodules.

This study was designed to explore further the hypothesis that the special resistance phenotype seen in hepatocyte nodules during liver carcinogenesis could have a physiologic correlate in the manner with which a carcinogenic xenobiotic is handled. Hepatocyte nodules were induced in male rats by continuous or intermittent exposure to dietary 2-acetylaminofluorene over a 25-week period. Two or 5 weeks after the exposure, the animals were given a single dose of 9-14C-2-acetylaminofluorene.

Inverse relationship between epidermal growth factor induced proliferation and expression of high affinity surface epidermal growth factor receptors in rat hepatocytes.

Rat hepatocytes express large numbers of high and low affinity surface membrane receptors (EGFR) for epidermal growth factor (EGF) but the roles of EGF and EGFRs in hepatocyte proliferation in vivo are unclear. F344 rat hepatocytes in primary culture proliferated maximally in response to continuous serum-free culture with 3.3 nM (20 ng/ml) EGF, as quantified by cumulative [3H]thymidine labeling index.

Quantification of cutaneous sensory nerves and their substance P content in psoriasis.

The aim of the present study was to extend our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic, and that substance P mediates the inflammation. For this purpose, the pattern of neurofilament-positive sensory nerve fibers was studied and the lengths and substance P content of these fibers measured morphometrically in dermal and epidermal compartments of the psoriatic lesion, psoriatic but lesion-free skin, and control skin. The epidermis and dermis of the psoriatic lesions were significantly more densely innervated with neurofilament-positive fibers than either lesion-free psoriatic or control skin.

Decreased cytosolic levels of the heme binding Z protein in rat hepatocyte nodules and hepatocellular carcinomas.

Hepatocyte nodules and hepatocellular carcinomas were induced in male Fischer rats using the resistant hepatocyte model. The immunoreactive cytosolic levels of the heme-binding Z protein (HBP) were reduced by 56% (P less than 0.001; 2-tailed t-test) in early hepatocyte nodules (25 weeks) and hepatocellular carcinomas (10-12 months).

The galactosyltransferase activity of hepatic nodules during rat liver carcinogenesis.

Galactosyltransferase has been isolated from putative preneoplastic hepatocyte nodules generated in the resistant hepatocyte model by the procedure of Solt et al. (Am. J.

Cancer development and its natural history. A cancer prevention perspective.

In the design of new approaches to cancer prevention, it is important to realize that most cancers develop stepwise over a long period of time with nonmalignant precursor lesions that only slowly evolve toward cancer. With many chemicals and some radiations, as well as some viruses (DNA and some retroviruses), cancer development can be divided into 3 major stages or periods, initiation, promotion and progression. Initiation is frequently associated with a more or less permanent change in the phenotype of a rare target cell, presumably due to a change in base composition in DNA or to gene rearrangements.

Glutathione and enzymes related to free radical metabolism in liver of rats fed a choline-devoid low-methionine diet.

Fischer F-344 male rats, fed a choline-devoid diet that leads to a highly reproducible sequence of biochemical and biological changes with an ultimate development of hepatocellular carcinoma, show elevated levels of glutathione in the liver at 3, 6 and 8 days. Several enzymes related to the metabolism of free radicals, including superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and DT-diaphorase show neither increased nor decreased activity as measured between 12 h and 8 days on the diet. Thus, of several known cellular components related to the possible scavenger of free radicals in the liver, only glutathione responded to the feeding of the CD diet.

Purification and characterization of P-52 (glutathione S-transferase-P or 7-7) from normal liver and putative preneoplastic liver nodules.

A previous study from our laboratory (L.C. Eriksson et al.

Decreased expression of cytochrome P-452 in the resistance phenotype characteristic of putative preneoplastic hepatocyte nodules during hepatocarcinogenesis.

Hepatocyte nodules, a characteristic early step in the development of liver cancer in rats, has a distinctive resistance phenotype including a large decrease in total cytochromes P-450 and in two isozymes induced by phenobarbital and two by 3-methylcholanthrene. In this study, it has been observed that the nodules show a large decrease in an additional cytochrome P-450, cytochrome P-452, which is very active in the hydroxylation of lauric acid at C-11 and C-12. The decrease in activity of this microsomal cytochrome P-452 is of the same order of magnitude as the decreases in the other cytochrome P-450 components.

DNA hypomethylation in ethionine-induced rat preneoplastic hepatocyte nodules.

DNA from hepatocyte nodules induced in rats with dietary DL-ethionine and from the surrounding non-nodular liver contained less 5-methyldeoxycytidine per deoxycytidine when compared with that from normal adult liver. The degree of apparent hypomethylation, 37% in nodules and 20% in the surrounding liver, decreased somewhat (29% and 16% respectively) at 2 weeks after terminating the exposure to ethionine. Nodules and surrounding liver, like normal liver, responded to partial hepatectomy with a decrease in the 5-methyldeoxycytidine level at 24 hrs and a return to the level at the time of partial hepatectomy by 38 hrs.

Initiators, promoters and the uncertainty principle.

The development of cancer in humans and in animals including experimental animals is almost always a multistep process. With carcinogenic chemicals and probably with some other etiological agents as well (e.g.

Morphometric evaluation of hepatocellular proliferative lesions in the rat liver.

Classification of rat hepatocellular proliferative lesions can vary between pathologists as the many qualitative histologic criteria have not been satisfactorily evaluated and ranked for prognostic value. Computer-assisted morphometry offers an objective method to evaluate certain cellular features. The Solt-Farber resistant hepatocyte model was used in this study to produce populations of rats with a full range of hepatocellular proliferative lesions.