Signal Transduction Mechanism for Serotonin 5-HT2B Receptor-Mediated DNA Synthesis and Proliferation in Primary Cultures of Adult Rat Hepatocytes.

The involvement of serotonin (5-hydroxytryptamine; 5-HT) and the 5-HT2 receptor subtypes in the induction of DNA synthesis and proliferation was investigated in primary cultures of adult rat hepatocytes to elucidate the intracellular signal transduction mechanisms. Hepatocyte parenchymal cells maintained in a serum-free, defined medium, synthesized DNA and proliferated in the presence of 5-HT or a selective 5-HT2B receptor agonist, BW723C86, but not in the presence of 5-HT2A, or 5-HT2C receptor agonists (TCB-2 and CP809101, respectively), in a time- and dose-dependent manner. A selective 5-HT2B receptor antagonist, LY272015 (10(-7) M), and a specific phospholipase C (PLC) inhibitor, U-73122 (10(-6) M), as well as specific inhibitors of growth-related signal transducers-including AG1478, LY294002, PD98059, and rapamycin-completely inhibited 5-HT (10(-6) M)- or BW723C86 (10(-6) M)-induced hepatocyte DNA synthesis and proliferation. Both 5-HT and BW723C86 were shown to significantly stimulate the phosphorylation of epidermal growth factor (EGF)/transforming growth factor (TGF)-α receptor tyrosine kinase (p175 kDa) and extracellular signal-regulated kinase (ERK) 2 on Western blot analysis. These results suggest that the proliferative mechanism of activating 5-HT is mediated mainly through 5-HT2B receptor-stimulated Gq/PLC and EGF/TGF-α-receptor/phosphatidylinositol 3-kinase (PI3K)/ERK2/mammalian target of rapamycin (mTOR) signaling pathways in primary cultured hepatocytes.

Responses of the photosynthetic apparatus to winter conditions in broadleaved evergreen trees growing in warm temperate regions of Japan.

Photosynthetic characteristics of two broadleaved evergreen trees, Quercus myrsinaefolia and Machilus thunbergii, were compared in autumn and winter. The irradiance was similar in both seasons, but the air temperature was lower in winter. Under the winter conditions, net photosynthesis under natural sunlight (Anet) in both species dropped to 4 µmol CO2 m(-2) s(-1), and the quantum yield of photosystem II (PSII) photochemistry in dark-adapted leaves (Fv/Fm) also dropped to 0.60. In both species the maximum carboxylation rates of Rubisco (V(cmax)) decreased, and the amount of Rubisco increased in winter. A decline in chlorophyll (Chl) concentration and an increase in the Chl a/b ratio in winter resulted in a reduction in the size of the light-harvesting antennae. From measurements of Chl a fluorescence parameters, both the relative fraction and the energy flux rates of thermal dissipation through other non-photochemical processes were markedly elevated in winter. The results indicate that the photosynthetic apparatus in broadleaved evergreen species in warm temperate regions responds to winter through regulatory mechanisms involving the downregulation of light-harvesting and photosynthesis coupled with increased photoprotective thermal energy dissipation to minimize photodamage in winter. These mechanisms aid a quick restart of photosynthesis without the development of new leaves in the following spring.

Responses of whole body protein synthesis and degradation to plantain herb in sheep exposed to heat.

An experiment including a [1-(13)C]leucine isotope dilution and a nitrogen balance were carried out to determine the effect of feeding plantain herb (Plantago lanceolata L.) on whole body protein synthesis (WBPS) and degradation in sheep kept at thermoneutral temperature (20 degrees C) or exposed to heat (30 degrees C). The animals were fed either mixed hay of orchardgrass and reed canarygrass (Hay-diet) or Hay-diet and plantain (9:1) (PL-diet) at maintenance level using a crossover design. Nitrogen intake was higher (p < 0.0001) for the Hay-diet than for the PL-diet, but N balance remained similar between diets and was higher (p = 0.003) during heat exposure than at thermoneutral temperature. The WBPS was numerically lower (p = 0.10) for the PL-diet than for the Hay-diet. The direction of the response to heat exposure differed (p = 0.04) between diets: after feeding the PL-diet the WBPS increased from 15.2-16.9 g x kgW(-0.75) x d(-1), whereas it decreased after feeding the Hay-diet from 17.5-16.6 g x kgW(-0.75) x d(-1). The present results suggest that the PL-diet may have a positive impact for WBPS during heat exposure, and could be used for rearing sheep as an alternative to the Hay-diet.

[Effect of ocular hypotensive medications in preventing the progression of visual field damage in patients with normal-tension glaucoma].

PURPOSE: We investigated the effect of ocular hypotensive medications and the risk factors for progression of visual field damage in patients with normal-tension glaucoma (NTG). SUBJECTS AND METHODS: Sixty-four NTG patients (64 eyes) followed at least 4 years with ocular hypotensive medications were studied regarding the probability of visual field stability using the Kaplan-Meier life-table analysis and multiple regression analysis with the Cox proportional hazards model. RESULTS: Probability of visual field stability was 56% at the 76-month follow-up. Mean intraocular pressure during the follow-up period and generalized cup enlargement type classified according to the optic disc shape were found to have significant influence on the progression of visual field damage. CONCLUSION: These findings suggest that ocular hypotensive medications are effective in stabilizing the visual field. We need to pay attention to the optic disc shape in patients with NTG.

[Postoperative results of non-penetrating trabeculectomy for primary open-angle glaucoma].

PURPOSE: To estimate the postoperative results of non-penetrating trabeculectomy(NPT), the success rate of postoperative intraocular pressure(IOP) and the clinical factors affecting postoperative IOP were evaluated. SUBJECTS AND METHODS: 32 eyes of 32 primary open-angle glaucoma(POAG) patients who underwent NPT as the first filtering surgery were enrolled in the study. We evaluated postoperative IOP using the Kaplan-Meier method, a proportional hazard model, and multiple logistic analysis. RESULTS: 53.2% of all patients had an IOP of less than 16 mmHg without antiglaucoma medication, and 63.8% had an IOP of less than 16 mmHg with antiglaucoma medication 36 months postoperatively. The performance of Nd:YAG trabeculopuncture(YLT) was indicated as a significant factor affecting postoperative IOP by the proportional hazard model(p = 0.037). 72.2% of patients who did not undergo YLT had an IOP of less than 16 mmHg without antiglaucoma medication, and 36.5% who underwent YLT had a postoperative IOP of less than 16 mmHg. There was significant difference between the both groups(log rank test, p = 0.045). Preoperative IOP with antiglaucoma medication was indicated as a significant factor affecting performance of YLT by multiple logistic analysis. CONCLUSION: These results suggest that NPT may be useful to reduce the use of antiglaucoma medication in patients with POAG whose preoperative IOP is controllable with antiglaucoma medication.

Correlation of blue chromatic macular sensitivity with optic disc change in early glaucoma patients.

PURPOSE: To investigate the relationship between morphological changes of the optic nerve head (ONH) and macular sensitivity determined with blue on yellow (B on Y) and white on white (W on W) perimetry in normal subjects and patients with glaucoma. METHODS: One randomly chosen eye was evaluated in each of 28 healthy subjects, 23 patients with ocular hypertension (OH), and 23 patients with early primary open-angle glaucoma (POAG). The mean macular sensitivity determined with B on Y and W on W perimetry was obtained by a macular program using a modified Humphrey field analyzer. The Heidelberg retina tomograph with software version 2.01 was used to evaluate the temporal topographic measurements of ONH. RESULTS: There was no significant difference in temporal ONH parameters among the three clinical groups. The mean macular sensitivity of B on Y and W on W perimetry in early POAG patients was significantly lower than that in healthy subjects and in patients with OH. The mean macular sensitivity of W on W perimetry showed no significant correlation with temporal ONH parameters in any clinical groups. In patients with early POAG, the mean macular sensitivity of B on Y perimetry was significantly related to cup area and volume, cup/disc area ratio, and rim volume in the temporal sector of the ONH. CONCLUSION: The measurement of the mean macular sensitivity of B on Y perimetry might make it possible to detect functional damage prior to morphological changes in the ONH due to elevated intraocular pressure in glaucoma.