Thyrotoxicosis with low serum total T3 level in patients with destructive thyroiditis and non-thyroidal illness.

The serum total T3 level, evaluated in 687 patients with thyrotoxicosis diagnosed by an elevated serum free T4 level and suppressed serum TSH level, was found to be high in 98.1% and normal in 1.9% of 592 patients with Graves' hyperthyroidism, and high in 75.8%, normal in 21.1% and low in 3.2% of 95 patients with destructive thyroiditis. Non-thyroidal illness was found in about a third of the patients with thyrotoxicosis and a normal serum total T3 level. The serum total T3 level was low with elevated serum thyroglobulin and reverse T3 levels in three patients with severe non-thyroidal illness, in whom the thyroidal radioactive iodine uptake was suppressed and the thyrotoxicosis resolved spontaneously with a normalization of the serum total T3 level after recovery from the destructive thyroiditis and non-thyroidal illness. It is therefore concluded that thyrotoxicosis with a low serum total T3 level, partially due to associated non-thyroidal illness, is more frequently found in patients with destructive thyroiditis than in those with Graves' hyperthyroidism.     

Enhancement of Saccharina kelp production by nutrient supply in the Sea of Japan off southwestern Hokkaido,Japan

Apart from certain studies on Macrocystis pyrifera (Linnaeus) C. Agardh, very few in situ experimental studies on production have been carried out to verify that “bottom–up effects” (relating to nutrient supply) are more important than “top–down” effects (relating to herbivory) in temperate kelp forests. The effects of nutrient supply on recruitment and production of hatchery-raised gametophytes of Saccharina japonica, cultivated on a rope, and wild Saccharina religiosa, cultivated on a rope and on new concrete reefs placed at the sea bottom, were examined at an experimental site with artificial nutrient addition continuously from October 2008 to May 2009 and compared to kelp that was cultivated from October 2008 to May 2009 without nutrient supply, at a natural site in Tomari (Sea of Japan, southwestern Hokkaido, Japan). At both sites, sea urchins were removed for exclusion of top–down effect. At the natural site, no hatchery-raised S. japonica and wild S. religiosa grew on the rope. No wild S. religiosa grew on the porous-concrete reefs and rocks. At the nutrient-enhanced site, S. japonica and S. religiosa grew rapidly on the rope, at rates of 47.7 and 33.3 plants/10 cm length rope, respectively. S. religiosa grew on the concrete reefs at a concentration of 9.7 plants/0.3 m². At the nutrient-enhanced site, the concentrations of NH₄-N, NO₃-N, NO₂-N, and PO₄-P ranged from 35.2–173.2, 2.1–10.9, 0.3–1.5, and 0.8–2.6 μmol L^?1, respectively, being markedly higher than those at the natural site, where these nutrient concentrations were almost equal to the averages off Tomari. These results indicate that the production of Saccharina kelp is restricted by bottom–up effects (at a low nutrient concentration) in the Sea of Japan, southwestern Hokkaido. Nutrient supply would be essential for growth enhancement of Saccharina kelp production in a marine environment around Japan where, in recent times, water temperatures have increased by ca. 0.5 °C and nutrient concentrations have decreased.     

Cytochrome 3A and 2E1 in human liver tissue: Individual variations among normal Japanese subjects

AimsThe metabolism of drugs, xenobiotic compounds, and other endogenous/exogenous substrates generally begins with their oxidation through cytochrome P450 (CYP). The results of recent pharmacogenetic analyses have demonstrated CYP's polymorphisms to be related to individual differences in metabolism, but only a limited number of CYP3A4 and CYP2E1 variant alleles influence enzymatic activities. Therefore, CYP gene expression profiling of both normal and pathological human livers should provide critical information for an evaluation of the biological significance of CYPs.Main methodsIn our present study, we first characterized the individual differences in CYP3A4 and CYP2E1 expression levels among Japanese normal or non-pathological liver tissue obtained from autopsy or surgery using immunohistochemistry and quantitative RT-PCR array of phase I metabolic enzymes with combined laser capture microscopy and qPCR analysis.Key findingsBoth CYP3A4 and CYP2E1 mRNA and proteins were predominantly detected in hepatocytes surrounding central veins in normal liver, but there were marked individual differences in both CYP3A4 and CYP2E1 mRNA and proteins among the 23 Japanese subjects examined. Individual differences in CYP3A and CYP2E1 subtypes were also detected in the livers obtained from monozygotic neonatal Japanese female twins with different survival periods. CYP3A and CYP2E1-positive cells were decreased in number in non-pathological hepatocytes of diseased livers compared to those in disease-free livers from autopsy.SignificanceThe above results suggest that individual differences in CYP3A4 and CYP2E1 exist among normal human liver tissues and in non-pathological hepatocytes between diseased and normal liver, and these differences may be important in evaluating the pharmacodynamics of various substances.     

Autophagy in the intestinal epithelium regulates Citrobacter rodentium infection

Autophagy, a ubiquitous degradation pathway, is important for the survival and homeostasis of cells. Previous studies have demonstrated the role of autophagy in host defense against bacterial infection, but the importance of autophagy in the intestinal epithelium for the regulation of bacterial infection has not been fully elucidated. In this study, we showed that the essential autophagy protein Atg7 is required for resistance to Citrobacter rodentium infection in the intestinal epithelium. Infected mice in which Atg7 had been conditionally deleted from the intestinal epithelium exhibited greater clinical evidence of disease and higher expression levels of pro-inflammatory cytokine mRNA in the large intestine. Moreover, C. rodentium clearance was reduced in the Atg7 conditional knockout mice. These results demonstrate that autophagy in intestinal epithelial cells plays an important role in host defense against C. rodentium infection and the regulation of C. rodentium infectious colitis.     

Design and synthesis of novel 1,25-dihydroxyvitamin D3 analogues having a spiro-oxetane fused at the C2 position in the A-ring

Four structurally novel stereoisomeric analogues of 1,25-dihydroxyvitamin D₃ (3a–d) bearing a spiro-oxetane fused at the C2 position of the A-ring have been designed and synthesised in a convergent manner. The requisite A-ring enyne precursors (13a,b) for the vitamin D analogues (3a,b) and (3c,d), respectively, were synthesised from pentaerythritol according to an eleven-step procedure. Preliminary biological evaluation of the analogues using the bovine thymus vitamin D receptor (VDR) suggested that the incorporation of the spiro-oxetane moiety instead of a gem-dimethyl group at the C2 position had a beneficial effect on the VDR affinity.     

Endosymbiosis of Chlorella species to the ciliate Paramecium bursaria alters the distribution of the host’s trichocysts beneath the host cell cortex

Each symbiotic Chlorella of the ciliate Paramecium bursaria is enclosed in a perialgal vacuole membrane derived from the host digestive vacuole membrane. Alga-free paramecia and symbiotic algae can grow independently. Mixing them experimentally can cause reinfection. Earlier, we reported that the symbiotic algae appear to push the host trichocysts aside to become fixed beneath the host cell cortex during the algal reinfection process. Indirect immunofluorescence microscopy with a monoclonal antibody against the trichocysts demonstrates that the trichocysts change their locality to form algal attachment sites and decrease their density beneath the host cell cortex through algal reinfection. Transmission electron microscopy to detect acid phosphatase activity showed that some trichocysts near the host cell cortex are digested by the host lysosomal fusion during algal reinfection. Removal of algae from the host cell using cycloheximide recovers the trichocyst's arrangement and number near the host cell cortex. These results indicate that symbiotic algae compete for their attachment sites with preexisting trichocysts and that the algae have the ability to ensure algal attachment sites beneath the host cell cortex.     

Dopamine D1 receptor signaling system regulates ryanodine receptor expression after intermittent exposure to methamphetamine in primary cultures of midbrain and cerebral cortical neurons

Regulatory mechanisms of ryanodine receptor (RyR) expression are not well known, although methamphetamine (METH) has been reported to up-regulate RyRs in mouse brain. This study investigate regulatory mechanisms of RyR expression by dopaminergic system using the midbrain and cerebral cortical neurons in primary culture intermittently exposed to METH and dopamine receptor (DR) agonists (1 h/day, for 3 days). Intermittent METH (10 μM) exposure enhanced RyR-1 and -2 proteins and their mRNA, but not RyR-3 expression in the both types of the neurons. These METH-induced increases of RyR proteins and their mRNA were dose-dependently blocked by SCH23390 (a selective D(1) DR antagonist), but not a D(2)DR antagonist sulpiride, suggesting a regulatory role of D(1)DRs in RyR expression by METH in these neurons. In cerebral cortical neurons, intermittent SKF82958 (a selective D(1)DR agonist) exposure increased RyR-1 and -2 proteins and their mRNA, whereas quinpirole (a selective D(2)DR agonist) showed no effects. KT5720, a protein kinase A inhibitor, dose-dependently attenuated the METH-stimulated RyR-1 and -2 expressions in cerebral cortical neurons. METH significantly increased phosphorylation of cAMP-response element-binding protein, which was completely suppressed by SCH23390. These results indicate that RyR-1 and -2 expressions are regulated by D(1)DRs via the signal transduction linked to D(1)DRs.     

FLAG-tag selective covalent protein labeling via a binding-induced acyl-transfer reaction

A FLAG tag selective protein labeling method is newly developed in this study. Coupling of the selective binding between synthetic Ni-complex probe and FLAG tag with the acyl transfer reaction enables the site-selective covalent modification of FLAG peptide and FLAG-tag fused protein.     

Muscle activation, cardiorespiratory response, and rating of perceived exertion in older subjects while walking in water and on dry land.

This study compared the muscle activities, cardiorespiratory responses, and ratings of perceived exertion (RPE) of nine older individuals while walking in water with those obtained while walking on dry land. Electromyography, stride frequency (SF), stride length (SL), oxygen uptake (V O(2)), heart rate (HR), RPE (for breathing and legs, RPE-Br and RPE-Legs, respectively), and blood lactate concentration (BLa) were measured. There were no significant differences in the V O(2), HR, RPE-Br, RPE-Legs or BLa while walking in water and on dry land (moderate and fast speeds). Both in water and on dry land, the V O(2)-HR, V O(2)-walking speed, and HR-walking speed relationships were significantly correlated. The SF and SL while walking in water were significantly lower than on dry land. The %MVCs while walking in water were all significantly lower than on dry land within each speed condition. Conversely, the V O(2), HR, RPE-Br and RPE-Legs, BLa, SL, and %MVC (the rectus femoris, vastus medialis, biceps femoris, and gastrocnemius) while walking in water were significantly higher than on dry land at the same speeds. In conclusion, walking in water elicits higher muscle activities, higher cardiorespiratory responses, and increased perceived exertion levels in older adults than walking on dry land at the same speed.