The effect of phototherapy on psychoautonomic disorders of a neurotic nature

Bright white light therapy was applied to 51 patients with syndrome of autonomic dysfunction of neurotic origin (1 hour of light exposure every day in the morning, during 2 weeks, 60 sm from the lamp, 3300 lux). Improvement occurred in 52% of the patients (responders--group 1, nonresponders--2). Changes occurred in nearly all symptoms: neuroendocrine, motivation, psychoautonomic, pain, psychopathologic. After the treatment in group 1 there was an increase of power of EEG spectrum, intensification of manifestations of the slow activity and decrease of the fast one from the two sides, an approach of the coefficient of asymmetry to the control levels as well as elevation of the urine excretion of metabolites of both catecholamines and serotonin. Initially higher power of EEG spectrum in group 2, became still more increased due to intensification of manifestations of theta and beta-2 rhythms from the two sides. Meanwhile coefficient of asymmetry was sharply decreased as well as general secretory activity inhibited. There were such symptoms and indices which had changed either negatively or positively under the influence of phototherapy.     

Crohn's disease and ulcerative colitis mucosal T cells are stimulated by intestinal epithelial cells: implications for immunosuppressive therapy

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases, and their pathogenesis is attributed, in part, to alterations of the mucosal immune system. This study was designed to define the possible contribution of epithelial cells to the activation of lamina propria T lymphocytes (LPTs) in CD and UC. METHODS: LPTs isolated from CD, UC, and control surgical specimens were cocultured with freshly isolated allogeneic or autologous epithelial cells or epithelial cell lines. Resulting T-cell proliferation was evaluated by tritiated thymidine incorporation on day 5. RESULTS: When intestinal epithelial cells were used to stimulate mucosal T-cell proliferation, CD and UC LPTs were less responsive than control LPTs (p < 0.05 and p < 0.03, respectively). This difference between inflamed and control T cells was consistently observed by using a variety of different intestinal epithelial cell types. CONCLUSIONS: CD and UC mucosal T cells are hyporesponsive to activation by intestinal epithelial cells when compared with control LPTs. Elucidating the mechanism underlying the differential activation of CD and UC LPTs may help to better understand the immunopathogenesis of these conditions.     

The m1 muscarinic acetylcholine receptor transactivates the EGF receptor to modulate ion channel activity

Intracellular tyrosine kinases link the G protein-coupled m1 muscarinic acetylcholine receptor (mAChR) to multiple cellular responses. However, the mechanisms by which m1 mAChRs stimulate tyrosine kinase activity and the identity of the kinases within particular signaling pathways remain largely unknown. We show that the epidermal growth factor receptor (EGFR), a single transmembrane receptor tyrosine kinase, becomes catalytically active and dimerized through an m1 mAChR-regulated pathway that requires protein kinase C, but is independent of EGF. Finally, we demonstrate that transactivation of the EGFR plays a major role in a pathway linking m1 mAChRs to modulation of the Kv1.2 potassium channel. These results demonstrate a ligand-independent mechanism of EGFR transactivation by m1 mAChRs and reveal a novel role for these growth factor receptors in the regulation of ion channels by G protein-coupled receptors.     

The L5178Y/tk+/- mouse lymphoma specific gene and chromosomal mutation assay a phase III report of the U.S. Environmental Protection Agency Gene-Tox Program

The L5178Y/tk+/- (-)3.7.2C mouse lymphoma assay (MLA) which detects mutations affecting the heterozygous thymidine kinase (tk) locus is capable of responding to chemicals acting as clastogens as well as point mutagens. Improvements in the assay to enhance detection of this spectrum of genetic events are summarized, and criteria for evaluating the data are defined. Using these criteria, the Phase III Work Group reviewed and evaluated literature containing MLA results published from 1976 through 1993. The data base included 602 chemicals of which 343 were evaluated as positive, 44 negative, 18 equivocal, 54 apparently inappropriate for evaluation in this test system with the published protocols, and 142 that were inadequately tested, and thus a definitive call could not be made. The overall performance of the assay is summarized by chemical class, and the outcome of testing 260 chemicals in the MLA is compared with Gene-Tox and National Toxicology Program evaluations of rodent carcinogenesis bioassay results for the same chemicals. Based on the Work Group's evaluation of published MLA data for chemicals that were considered adequately tested, it is concluded that for most chemicals the L5178Y/tk+/- mouse lymphoma assay is eminently well suited for genotoxicity testing and for predicting the potential for carcinogenicity.     

Regenerating sciatic nerve does not utilize circulating cholesterol

Vascular endothelial growth factor (VEGF) is a major contributor to retinal neovascularization. The possible participation of VEGF and its high-affinity tyrosine kinase receptors, flk-1 and flt-1, in early background diabetic retinopathy was studied in the streptozotocin-induced diabetic rat model of experimental retinopathy using in situ hybridization, blotting techniques, and immunohistochemistry. Diabetic retinopathy was assessed by quantitative morphometry of retinal digest preparations. The number of acellular capillaries increased 2.7-fold in diabetic animals with diabetes' duration of 6 months compared with nondiabetic controls. VEGF expression was not detectable by in situ hybridization in nondiabetic rats but was highly increased in the ganglion cell layer and in the inner and outer nuclear layers of retinas from diabetic animals. VEGF protein was extractable only from diabetic retinas, and a strong immunolabeling was detected in vascular and perivascular structures. Increased flk-1 and flt-1 mRNA levels were also found in the ganglion cell and both nuclear layers of diabetic samples only. Dot blot and Western blot analyses confirmed the increase in flk-1 mRNA and protein in diabetic retinas. Also, flk-1 immunoreactivity was associated with vascular and nonvascular structures of the inner retinas from diabetic animals. These data obtained from a rodent model in which retinal neovascularization does not occur support the concept that the VEGF/VEGF receptor system is upregulated in early diabetic retinopathy.     

Use of electrophoretic karyotyping and DNA-DNA hybridization in yeast identification

The behavioral disturbances of 16 nursing home patients with a history of sundowning behaviour and dementia were treated with light therapy instead of psychopharmacological medication. After the withdrawal of the before established medication a very individual, heterogenous deterioration of the symptoms was noted. A significant improvement of the behaviour was not found by light therapy in any patient. The problems in practical handling and possible consequences of further investigation are discussed.     

Circulating angiotensin II and renal sodium handling in man: a dose-response study

1. Animal studies have shown that angiotensin II has a biphasic effect on urinary sodium excretion. To examine whether this is also true in man, we studied seven salt-replete male subjects in a single-blind placebo-controlled manner. 2. While undergoing maximum diuresis, subjects were infused with 0, 1, 2, 5 or 10 ng of angiotensin II min-1 kg-1 over 80 min. Subjects were studied while seated, and stood every 20 min for urine collection. 3. Angiotensin II produced a dose-dependent antidiuretic effect. The urine flow rate, in ml/min expressed as the change from baseline with increasing dose of angiotensin, was: +3.4 +/- 1.77, -1.26 +/- 0.49 (P < 0.05), -2.75 +/- 1.23 (P < 0.05), -4.21 +/- 0.82 (P < 0.05) and -6.51 +/- 1.07 (P < 0.01). 4. In contrast, the effect of angiotensin II on sodium excretion showed a flat dose-response curve beyond 5 ng min-1 kg-1. The urinary sodium excretion, in mumol/min expressed as the change from baseline with increasing dose of angiotensin, was: 9.5 +/- 21.2, -18.9 +/- 29.6, -37.0 +/- 11.6 (P < 0.05), -67.7 +/- 19.6 (P < 0.01) and -63.8 +/- 14.3 (P < 0.01). 5. The fractional distal reabsorption of sodium, determined by using the lithium clearance technique, showed a rise with all doses of angiotensin II used and reached statistical significance with the top two doses. 6. Unlike antidiuresis, antinatriuresis after graded doses of angiotensin II in human subjects showed a flat dose-response curve beyond 5 ng min-1 kg-1. Pressor doses of angiotensin II also have a significant effect on the distal tubule in promoting sodium reabsorption.     

Prenatal exposure to methylmercury alters locomotor activity of male but not female rats

In the present study the neurotoxic effects of a low dosage (0.5 mg/kg per day) of methylmercury (MeHg) on the developing nervous system were investigated. Pregnant rats were treated with MeHg from day 7 of pregnancy to day 7 of lactation. Locomotor activity (locomotion, rearing, and motility) and spatial learning ability were tested in the offspring at 6 months of age. The expression of tyrosine hydroxylase (TH) was examined by immunohistochemistry and in situ hybridization. A significant decrease in spontaneous motility and rearing was observed only in the MeHg-treated male rats. After administration of a low dose of d-amphetamine (0.5 mg/kg) no differences could be observed between control and MeHg-treated male rats, suggesting that changes in dopaminergic transmission were involved. However, no change in TH messenger RNA expression was observed. No changes in spatial learning acquisition or memory were shown in MeHg-treated rats. Taken together, these findings show that during development a very low dosage of MeHg exerts neurotoxic effects detectable in adulthood, and that susceptibility is gender-dependent.     

Granulation tissue polyposis associated with carcinoid tumours of the small intestine

We report two patients with ileal carcinoid tumours which were associated with polyps due to mucosal granulation tissue proliferation. In both cases the tumours had extensively infiltrated the small bowel wall and mesentery, and one had hepatic metastases. The mucosal surface of each specimen showed numerous, pale brown, sessile polyps which were restricted to the intestinal segment involved by carcinoid tumour, although not always closely related to neoplastic cells. The polyps were formed by the proliferation of capillaries, smooth muscle cells and myofibroblasts as demonstrated by immunohistochemistry and electronmicroscopy.