Effect of dietary omega-3 and omega-6 fatty acid sources on PUVA-induced cutaneous toxicity and tumorigenesis in the hairless mouse

Because of concern about psoralen-induced phototoxicity and photocarcinogenesis, we investigated the effects of dietary lipids in a mouse model in which 8-methoxypsoralen (8-MOP) and UVA (PUVA) therapy has been shown to be carcinogenic. SKH-Hr-1 hairless albino mice were fed diets containing either omega-3 or omega-6 fatty-acid sources (menhaden oil and corn oil, respectively). After 2 weeks on the diets, the mice were treated topically with 8-MOP and then exposed to UVA (5 J/cm²). Mice receiving the omega-3 fatty-acid source exhibited a marked decrease in inflammatory response and a more rapid repair, as expressed both grossly and microscopically. In support of the latter response, i.e. repair, ornithine decarboxylase activity was about 20% greater in animals receiving the omega-3 fatty-acid source. The effects of the dietary fatty acid sources on PUVA tumorigenesis were examined in long-term studies in which animals were treated topically with 0.01% 8-MOP thrice weekly after which they were exposed to UVA (1 J/cm²). These studies indicated that a dietary lipid rich in omega-3 fatty acid and known to exhibit anti-inflammatory properties can markedly ameliorate the course of PUVA toxicity but does not impede the course of PUVA tumorigenesis     

Coexistence of autonomic and somatic mechanisms in the pressor areas of medulla in cats.

The effects of electrical stimulation and microinjection of sodium glutamate (0.5 M) in the sympathetic pressor areas of the dorsal medulla (DM), ventrolateral medulla (VLM), and parvocellular nucleus (PVC) on the knee jerk, crossed extension, and evoked potential of the L5 ventral root produced by intermittent electrical stimulation were studied in 98 adult cats anesthetized with chloralose and urethane. During electrical and glutamate stimulation of these pressor areas, in addition to the rise of systemic arterial blood pressure marked inhibition of the spinal reflex was produced, indicating presence of neuronal perikarya responsible for these actions. Mild to moderate augmentation of spinal reflexes was also observed during brain stimulation but only in a few cases. The magnitude of the somatic effects among the pressor areas of the VLM, DM, and PVC subsequent to glutamate activation was about the same. Induced spinal reflex inhibition, independent from the baroreceptor and vagal influence, remained essentially unaltered after acute midcollicular decerebration. The inhibition was also observed in cats decerebellated 8-10 days in advance. The inhibition was not affected after bilateral electrolytic- or kainic-acid-induced lesions in the paramedian reticular nucleus (PRN). On the contrary, PRN-induced spinal reflex inhibition was attenuated after bilateral lesions in the DM or VLM. Data suggest that there coexists neuronal subpopulations in the VLM, DM, and PVC that can affect both the sympathetic pressor systems and spinal reflexes.     

An electron microscopic study of migrating cells in the nasal epithelial compartment of human allergic rhinitis

Since intraepithelial migrating cells are the first to come into contact with various foreign particles inhaled and deposited on the nasal surface, it is important to study the distribution and function of these cells in the epithelial layer of nasal mucosa. We examined nasal scrapings by means of electron microscopy and electron microscope immunocytochemistry and found that lymphocytes were the major population in the epithelial layer, followed by eosinophils, basophilic cells, globule leukocytes and neutrophils in the order of predominance in patients with allergic rhinitis. However, no significant difference was noted in lymphocyte population between the allergy group and the chronic infectious rhinitis group, while significant increase was found in the normal group than in other two groups. Meanwhile, significant difference of eosinophils and basophilic cells were found between allergic group and non-allergic group. Globule leucocytes, characterized by their huge and irregular size and granules, were observed in the allergy group and the implication of their existence was discussed. In immunoelectron microscopic study, CD8 positive cells were more numerous than CD4 positive cells. However there was no relation between the surface marker and ultrafine structure.     

Skeletal effects of calcitonin in ovariectomized rats

Although calcitonin (CT) has been shown to be effective for the prevention of bone loss in early postmenopausal women, the skeletal effects of the hormone specifically during the early stages of estrogen deficiency have not been characterized histomorphometrically to date. The current study involves use of the ovariectomized (OVX) rat as an animal model for early postmenopausal bone loss to perform such a histomorphometric analysis. One group of OVX rats was injected sc with salmon CT on alternate days for a 6-week period. Additional groups of OVX and sham-operated control rats were treated with vehicle alone. In comparison to control rats, the proximal tibia of vehicle-treated OVX rats were characterized by a 3-fold decrease in cancellous bone volume and significant increases in osteoblast surface (+200%), osteoclast surface (+143%), mineralizing surface (+111%), mineral apposition rate (+36%), bone formation rate (+181%), and longitudinal bone growth (+38%). In contrast, treatment of OVX rats with CT normalized tibial cancellous bone volume and significantly decreased all of the above cellular- and fluorochrome-based indices of bone turnover to near control levels. The results indicate that CT treatment depresses bone turnover and prevents the development of osteopenia in OVX rats. These findings are consistent with the bone protective effect of CT in early postmenopausal women and further support the OVX rat as an animal model for the preclinical evaluation of prophylactic treatments for postmenopausal bone loss.     

Analysis of pivotal-differential evolutionary patterns

The numerical analysis of meiosis in hybrids between a wild allotetraploid and an autotetraploid of one of its putative diploid progenitors allows the identification of which genomes are pairing and also the verification of pivotal-differential evolution. This type of analysis should be applicable to all genera in which allopolyploid series exist.     

Tau assembly in inducible transfectants expressing wild-type or FTDP-17 tau

Conditional expression systems for 4-repeat wild-type (WT) tau or the corresponding mutants V337M and R406W were established in human neuroglioma H4 cells to study the effect of tau mutations on the physicochemical properties of tau, and to develop a cellular model for the formation of filamentous tau characteristic of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) and Alzheimer's disease. Upon induction tau expression increased, reaching maximal levels at 5 to 7 days. WT tau was phosphorylated at amino acids T181, S202/T205, T231, and S396/S404. The R406W mutation decreased tau phosphorylation at each of these sites as did the V337M mutation except for S396/S404 sites that increased. Most tau in postnuclear cell lysates was recovered in the supernatant fraction after centrifugation at 200,000 x g. The amount of tau in the pellet fraction increased more in mutant transfectants compared to WT when the induction was extended beyond 5 days. This particulate tau could be partially extracted with salt, Triton X-100, or sarkosyl. Of the transfectants, R406W had the highest proportion of sarkosyl-insoluble tau by day 7. This insoluble fraction was thioflavin S-positive and contained 15- to 5-nm-wide filaments with tau immunoreactivities. The R406W filaments were more abundant than those detected in similar preparations from WT or V337M transfectants. At the light microscopy level, most tau was found with microtubules, or diffusely distributed in the cytoplasm, but none of this appeared thioflavin S-positive. The results suggest that conditional tau transfectants are in a pretangle stage making them an attractive model system for studying intracellular tangle accumulation and for testing potential therapeutic agents as inhibitors for tau aggregation.