The role of thromboxane A2 [TxA2] in liver injury in mice

The role of thromboxane A2 (TxA2) in CCl4-induced liver disease was investigated in mice. Significant elevation of TxB2 in the liver was observed 6 hours after the injection of CCl4. Administration of OKY-046, a selective TxA2 synthetase inhibitor (10 and 50 mg/kg) and ONO-3708, a TxA2 receptor antagonist, (0.5, 1 and 2 mg/Kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes of the liver. In addition, OKY-046 inhibited the elevation of TxB2 in the liver. When U-46619, a stable TxA2 mimetic was injected i.v. into the mice, clear elevation of serum GOT and GPT levels and histopathological score of the liver were observed. These results suggest that TxA2 play a role for the onset of CCl4-induced liver injury in mice.     

Phylogeny of gymnosperms inferred fromrbcL gene sequences

Partial nucleotide sequences of the large subunit of ribulose-1,5-bisphosphate carboxylase (rubisco) gene (1333 base pairs: about 90% of the gene) from several seed plants were determined. Phylogenetic trees based on amino acid sequences were inferred by using the neighbor joining and maximum likelihood methods. The results indicate (1) monophyly of gnetum group (Ephedra, Gnetum, Welwitschia), (2) monophyly of extant gymnosperms containing gnetum group, which contradicts the results of morphological data.     

Construction of Libraries for Methylation Sites by In-gel Competitive Reassociation (IGCR)

The in-gel competitive reassociation (IGCR) procedure was successfullyapplied to construct a comprehensive library enriched in DNAfragments containing C^5mCGG sequences from mouse liver and braingenomic DNA. For IGCR, methylation-insensitive restriction enzyme(Msp I) digests were used as target DNA and methylation-sensitiverestriction enzyme (Hpa II) digests as competitor DNA. Southernblot analysis indicated that 60 to 70% of the clones in thelibrary were derived from the methylated sites and overall enrichmentwas 200- to 1000-fold. IGCR was further applied to constructa library for the sites differentially methylated between brainand liver DNA. In the library, approximately 20% of the HpaII sites exhibited different degrees of methylation betweenthese tissues.     

Molecular phylogeny in the Lardizabalaceae

Eleven species belonging to seven genera in the Lardizabalaceae were analyzed in terms of restriction fragment length polymorphism (RFLP) of chloroplast DNA and the sequence of the chloroplast gene,rbcL, of Lardizabalaceae and its related families. Phylogenetic trees inferred from parsimony, neighbor joining and maximum likelihood methods based on RFLP data showed that two South American genera,Boquila andLardizabala, and three East Asian genera,Akebia, Holboellia andStauntonia are closely related to each other, respectively. On the other hand, the parsimony, neighbor joining and maximum likelihood trees constructed using sequence data of therbcL gene showed thatAkebia, Stauntonia, Boquila andLardizabala clustered as(((Akebia, Stauntonia), Boquila), Lardizabala). This difference may be attributable to fewer informative sites inrbcL genes than in RFLP in this family.Decaisnea diverges at the very base of the Lardizabalaceae.     

Differences in liver homogenates from Donryu, Fischer, Sprague-Dawley and Wistar strains of rat in the drug-metabolizing enzyme assay and the salmonella/hepatic S9 activation test

Comparison studies for detecting differences between liver microsome and S9 preparations from 4 strains (Donryu, Fischer, Sprague-Dawley, Wistar) of young male rats were carried out with pretreatment of the animals by inducers such as PCBs and PB plus 5,6-BF. Each microsome fraction was assayed for the enzymic activity of metabolism of model substrates such as aniline, benzophetamine, BP, DMN and 7-ethoxycoumarin. The hepatic S9 sample was also compared, as regards its metabolizing ability to activate 9 pre-mutagens (2AA, AAF, o-AAT, BP, DAB, DMBA, DMN, m-PDA, quinoline) to directly acting mutagens in the Salmonella/hepatic S9 activation test by using TA98, TA100 and TA1537 strains with or without cytochrome P450 inhibitors (SKF-525A, metyrapone, 7,8-benzoflavone).In the enzymic assay with PCBs-induced microsomes, BP hydroxylation revealed a strain-specific difference: the microsomes from Fischer and Wistar rats were more effective for metabolizing BP than those from the other strains of rat. The effect of induction by PB plus 5,6-BF for Fischer rats showed relatively higher enzymic activity in the same induction group. Other microsomes prepared from rats with and without induction by PB plus 5,6-BF did not show a clear-cut strain dependency in the enzymic activities assayed.In the mutation experiments with hepatic S9 samples, the examination of DAB and quinoline revealed a marked strain difference when S9 samples prepared from PCBs-pretreated and PB-plus-5,6-BF-induced rats were used: the S9 sample from Fischer rats was available for activating the two pre-mutagens to directly acting mutagens. No marked difference in the metabolic activation of the remaining 7-pre-mutagens was observed on other S9 preparations.In examinations of mutagenicity activities with the use of three inhibitors, the two S9 preparations made with the two induction methods showed inhibition profiles closely similar to each other. However, there were minor differences in the profiles by these inhibitors.From these findings it was concluded that Fischer rat-liver S9 is useful for detecting mutagens in the metabolic activation test, when induction by PB plus 5,6-BF was used in the Ames Salmonella test.     

Refractoriness to phosphaturic action of parathyroid hormone occurring independent of phosphate depletion in hyperparathyroid rats

In an attempt to clarify the underlying mechanism(s) in the disappearance of phosphaturic response to bolus parathyroid hormone (PTH) in hyperparathyroid patients, the effects of bolus bovine PTH (10 USP U) were studied in conscious thyroparathyroidectomized (T . PTX) male Wistar rats that had been infused with a dose of PTH (2.5 U/hr, for 16 hours) so as to reproduce hyperparathyroidism. These animals responded with an increase in urinary cyclic AMP, but without an increase in renal clearance of phosphate. The loss of phosphaturic response was not prevented by pretreatment with actinomycin D at a dosage close to full toxicity (0.1 mg/kg BW, ip, for 3 days). Actinomycin D at this dosage did not affect the normal stimulatory effects of bolus PTH on urinary cyclic AMP and renal clearance of phosphate in T . PTX rats. The continuous infusion of PTH produced nearly maximal phosphaturia throughout in the face of a significant depletion of phosphate. In addition, pretreatment with actinomycin D did not cause a further increase in urinary phosphate excretion during the infusion. These results, along with the report of Shah et al. (1979) indicating that the development of antiphosphaturic adaptation to acute phosphate depletion was prevented by comparable amounts of actinomycin D, indicate that the disappearance of phosphaturic response to bolus PTH by prior PTH infusion simply signifies the continuation of maximal phosphaturic response to the preceding PTH infusion. It is also suggested that the continuous action of PTH prevents, at least phenomenologically, the development of the gene-activation-mediated refractoriness to PTH or antiphosphaturia induced by acute phosphate depletion.     

Salmon calcitonin-induced stimulation of 1 alpha,25-dihydroxycholecalciferol synthesis in rats involving a mechanism independent of adenosine 3'':5''-cyclic monophosphate.

The effect of natural salmon calcitonin on accumulation in plasma of 1 alpha,25-dihydroxy-[3H]cholecalciferol from 25-hydroxy[3H]cholecalciferol in vivo was investigated in vitamin D-deficient thyroparathyroidectomized rats into which graded doses of the hormone were continuously infused by use of a balance study system. A dose-dependent increase in plasma concentrations of 1 alpha,25-dihydroxy[3H]cholecalciferol was observed with calcitonin infusion for 6--30h at a rate greater than 20 M.R.C. m-units/h. Infusion of parathyrin or cyclic AMP produced a similar stimulation [Horiuchi, Suda, Takahashi, Shimazawa & Ogata (1977) Endocrinoly 101, 969--974], but the maximal effect of calcitonin was additive to that of either parathyrin or cyclic AMP. Furthermore concurrent infusion of theophylline (0.5 mumol/h) did not potentiate the effect of submaximal doses (3 and 20 M.R.C. m-units/h) of calcitonin. Plasma concentrations of calcium showed a decrease with calcitonin infusion for 30h, but those of Pi remained unchanged. These results strongly suggest that the rat kidney is endowed with a calcitonin-sensitive 1 alpha-hydroxylase system that is separate from the parathyrin/cyclic AMP system and is independent of changes in plasma Pi.     

Characteristics of stable isotope signature of diet in tissues of captive Japanese macaques as revealed by controlled feeding

We determined the magnitude of isotopic fractionation of carbon and nitrogen stable isotope ratios (as enrichment factors, Δδ¹³C and Δδ¹⁵N, respectively) between the tissues and diets of captive Japanese macaques (Macaca fuscata) using a controlled feeding experiment, to provide basic data for reconstructing their feeding habits. The Δδ¹³C and Δδ¹⁵N values, respectively, were 0.9 ± 0.2 ‰ (mean ± standard deviation, SD) and 3.0 ± 0.3 ‰ for whole blood, 1.3 ± 0.2 ‰ and 4.3 ± 0.3 ‰ for plasma, and 0.8 ± 0.2 ‰ and 3.0 ± 0.2 ‰ for red blood cells. However, the Δδ¹³C and Δδ¹⁵N values for hair were 2.8 ± 0.3 ‰ and 3.4 ± 0.2 ‰, respectively. No difference was detected in the δ¹³C and δ¹⁵N values of hair sampled from different parts of the body. We investigated the effects of diet on δ¹³C in growing hair by alternating the diet of the macaques each month between two diets that differed markedly in δ¹³C. Hair regrown after shaving repeatedly recorded the δ¹³C of the diet consumed during the time of hair growth. On the other hand, hair naturally grown during the diet-change experiment did not show a clear pattern. One possible reason is that the hair had grown abnormally under unnatural indoor conditions and showed complicated isotope signatures. To reconstruct the long-term feeding history of Japanese macaques, we need to further clarify the relationships between the stable isotope signature of diet and various body tissues.     

Relative sea‐level change regulates organic carbon accumulation in coastal habitats

Because coastal habitats store large amounts of organic carbon (C_org), the conservation and restoration of these habitats are considered to be important measures for mitigating global climate change. Although future sea‐level rise is predicted to change the characteristics of these habitats, its impact on their rate of C_org sequestration is highly uncertain. Here we used historical depositional records to show that relative sea‐level (RSL) changes regulated C_org accumulation rates in boreal contiguous seagrass–saltmarsh habitats. Age–depth modeling and geological and biogeochemical approaches indicated that C_org accumulation rates varied as a function of changes in depositional environments and habitat relocations. In particular, C_org accumulation rates were enhanced in subtidal seagrass meadows during times of RSL rise, which were caused by postseismic land subsidence and climate change. Our findings identify historical analogs for the future impact of RSL rise driven by global climate change on rates of C_org sequestration in coastal habitats.     

The Protective Effects of Levetiracetam on a Human iPSCs-Derived Spinal Muscular Atrophy Model

Neurochemical Research - Spinal muscular atrophy (SMA) is an inherited disease characterized by progressive motor neuron death and subsequent muscle weakness and is caused by deletion or mutation...