Mechanism for the induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase in HgCl2-treated sweet potaso root tissue

No 3-hydroxy-3-methylglutaryl coenzyme A reductase activitywas detected in microsomal fractions prepared from healthy andwounded sweet potato root tissues. However, there was considerableenzyme activity in the tissue discs when Hgcl₂ was applied afterincubation at 30?C for 18 hr. This increase in the enzyme activitywas followed by furano-terpene accumulation. Application ofcycloheximide to discs immediately after preparation completelyinhibited the increase in the enzyme activity when HgCl₂ wasapplied after incubation. In contrast, the increase was delayedfor about 4 hr, then the activity was enhanced, when CHI wasapplied after preliminary incubation. CHI completely inhibitedprotein synthesis when applied to the discs after the preliminaryincubation, as judged by the inhibition of the incorporationof ¹⁴C-leucine into protein and the inhibition of the increasein peroxidase activity which is synthesized de novo. These resultssuggest that the inactive precursor of HMG-CoA reductase issynthesized during the preliminary incubation in response onlyto wounding then it is converted into the active form aftertreatment with HgCl₂. (Received January 11, 1979; )     

<Emphasis Type="Italic">Streptococcus pyogenes</Emphasis>-purpura fulminans as an invasive form of group A streptococcal infection

Background

Streptococcus pyogenes is an uncommon pathogen of purpura fulminans, and the pathogenesis of S. pyogenes-purpura fulminans remains unclear because of paucity of cases. We reported a pediatric case of S. pyogenes-purpura fulminans with literature review of the disease.

Case presentation

A 3-year-old boy showed limping, lethargy and acral gangrene within 24 h. A diagnosis of S. pyogenes-purpura fulminans was made for bacterial isolation from throat and peripheral blood. Intensive therapy led to a survival with amputation of the left distal metatarsal bone, and normal development. The isolated M12 carried no mutation of csrS/R or rgg. Thrombophilia or immunodeficiency was excluded.

Discussion

Twelve-reported cases (9 pediatric and 3 elderly) of S. pyogenes-purpura fulminans started with shock and coagulopathy. Five patients age <?8 years had no underlying disease and survived. One youngest and two immunocompromised patients died.

Conclusion

Streptococcus pyogenes-acute infectious purpura fulminans is a distinctive rare form of aggressive GAS infections.

     

A new comprehensive method for detection of livestock-related pathogenic viruses using a target enrichment system

We tested usefulness of a target enrichment system SureSelect, a comprehensive viral nucleic acid detection method, for rapid identification of viral pathogens in feces samples of cattle, pigs and goats. This system enriches nucleic acids of target viruses in clinical/field samples by using a library of biotinylated RNAs with sequences complementary to the target viruses. The enriched nucleic acids are amplified by PCR and subjected to next generation sequencing to identify the target viruses. In many samples, SureSelect target enrichment method increased efficiencies for detection of the viruses listed in the biotinylated RNA library. Furthermore, this method enabled us to determine nearly full-length genome sequence of porcine parainfluenza virus 1 and greatly increased Breadth, a value indicating the ratio of the mapping consensus length in the reference genome, in pig samples. Our data showed usefulness of SureSelect target enrichment system for comprehensive analysis of genomic information of various viruses in field samples.     

Inhibition of Zn2+-induced potentiation of twitch tension by Ni2+ in frog muscle

Effect of Ni2+ on Zn2+-induced potentiation of twitch tension was studied electrophysiologically in the toe muscle fibers of Rana catesbeiana. The major findings of this investigation are as follows. When 2 mM Ni2+ was applied to fibers in a normal Ringer's solution containing 50 microM Zn2+ (Zn2+ solution), the Zn2+-potentiated twitch tension decreased remarkably to about one-third of that before Ni2+ treatment. This concentration of Ni2+ caused a 23% decrease in the duration of action potential which had been prolonged by Zn2+ (6.61-5.09 ms). Ni2+ (2 mM) added to normal Ringer's solution led to increases of about 30 and 42% in twitch tension and in the duration of action potential, respectively. A slight increase in the mechanical threshold was induced by 2 mM Ni2+. The inhibitory action of Ni2+ on the twitch tension in Zn2+ solution was larger than that in the case of tetanus tension. Diltiazem (40 microM), a Ca2+ channel blocker, did not inhibit the twitch tension potentiated in Zn2+ solution. These results suggest that the decrease in Zn2+-potentiated twitch tension by Ni2+ may possibly derive from impairment of the propagation of action potential along the T tubules.     

Modulation of the Ca2+ channel voltage sensor and excitation-contraction coupling by silver.

Ag+ (0.5-10 microM) is known to produce a transient contraction of intact frog skeletal muscle fibers followed by complete inhibition of excitation-contraction (E-C) coupling. We have carried out physiological and biochemical experiments to investigate the basis of this effect. Dihydropyridine (DHP) Ca2+ channel blockers, which inhibit the voltage sensor of the Ca2+ channel, completely inhibit Ag+ contractions. Removal of extracellular Ca2+, or blockade of Ca2+ entry with cadmium, does not inhibit Ag+ contractions. Activation of the Ca2+ channel's voltage sensor with the Ca2+ channel agonists Bay K 8644 or with perchlorate, potentiates the Ag(+)-induced contraction. Ag+ binds to the partially purified rabbit skeletal muscle Ca2+ channel and inhibits DHP binding (IC50 = 1.1 microM) and sulfhydryl (SH) reactivity (IC50 = 0.11 microM) over the concentration range where it inhibits E-C coupling. Oxidation of free SH groups by H2O2 or their reaction with DTNB prevents Ag+ contractions, while DTT reduction of oxidized SH groups restores Ag+ contractions. These results suggest that Ag+ binds to critical SH groups on the DHP receptor Ca2+ channel, resulting in modification of the channel's voltage sensor and the failure of E-C coupling.     

Efficacy of adjuvant Immunochemotherapy with polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials

The benefits of immunochemotherapy employing the biological response modifier polysaccharide K (PSK) for patients with curatively resected colorectal cancer was reassessed by means of a meta-analysis of data with center randomization from 1,094 patients enrolled in three clinical trials. In all three trials, patients were followed up for at least 5 years after surgery and enrollment of the last patient and outcomes for standard chemotherapy were compared with those for chemotherapy plus PSK. The endpoints were overall survival and disease-free survival; and intent-to-treat analysis was performed without patient exclusion. Data were analyzed using the weighted average of the individual log hazard ratios. The overall survival risk ratio for all eligible patients was 0.71 (95% confidence interval (CI) : 0.55–0.90; P=0.006), and the disease-free survival risk ratio was 0.72 (95% CI: 0.58–0.90; P=0.003). The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK can improve both survival and disease-free survival of patients with curatively resected colorectal cancer.     

Subchronic stress-induced depressive behavior in ovariectomized mice

AimsMood disorders including depression are more common in women than men, particularly in times of lower estradiol levels. In this study, we investigated the effect of estrogen on emotional behavior in mice in a stress environment.Main methodsFemale mice were divided into four groups: two groups were ovariectomized (OVX) and two were sham-operated. One group each of OVX and sham mice was kept in a normal environment and the other groups were assigned to a daily stress (1 h/day) for 7 days from 5 days after operation. On the 14th day after operation, subjects were measured to assess behavioral specificity, locomotor activity, elevated plus-maze (EPM) behavior, passive avoidance (PA) behavior and forced swimming behavior.Key findingsThe OVX plus stress (OVX + S) group showed a significant prolongation of immobility compared with the other groups. In all the groups there were no changes in locomotor activity, EPM behavior or PA behavior. We further examined the effect of estrogen against depressive behavior in the OVX + S group. The vehicle or 17β-estradiol (E2) was administered s.c. to OVX + S mice for 4 days beginning on post-operative day 11. Subchronic E2 treatment decreased the stress response and improved depressive behavior relative to the vehicle group.SignificanceThese data have important implications regarding the prevention of depression in postmenopausal women undergoing estrogen therapy.     

Multidrug-resistance-associated protein plays a protective role in menadione-induced oxidative stress in endothelial cells

AimsMenadione, a redox-cycling quinone known to cause oxidative stress, binds to reduced glutathione (GSH) to form glutathione S-conjugate. Glutathione S-conjugates efflux is often mediated by multidrug-resistance-associated protein (MRP). We investigated the effect of a transporter inhibitor, MK571 (3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid), on menadione-induced oxidative stress in bovine aortic endothelial cells (BAECs).Main methodsBAECs were treated with menadione and MK571, and cell viability was measured. Modulation of intracellular GSH levels was performed with buthionine sulfoximine and GSH ethyl ester treatments. Intracellular superoxide was estimated by dihydroethidium oxidation using fluorescence microscopy or flow cytometry. Expression of MRP was determined by flow cytometry using phycoerythrin-conjugated anti-MRP monoclonal antibody.Key findingsIntracellular GSH depletion by buthionine sulfoximine promoted the loss of viability of BAECs exposed to menadione. Exogenous GSH, which does not permeate the cell membrane, or GSH ethyl ester protected BAECs against the loss of viability induced by menadione. The results suggest that GSH binds to menadione outside the cells as well as inside. Pretreatment of BAECs with MK571 dramatically increased intracellular levels of superoxide generated from menadione, indicating that menadione may accumulate in the intracellular milieu. Finally, we found that MK571 aggravated menadione-induced toxicity in BAECs and that MRP levels were increased in menadione-treated cells.SignificanceWe conclude that MRP plays a vital role in protecting BAECs against menadione-induced oxidative stress, presumably due to its ability to transport glutathione S-conjugate.     

Efficacy of Integrating Herder Knowledge and Ecological Methods for Monitoring Rangeland Degradation in Northern Kenya

The world-wide debate on land degradation in arid lands, usually linked to local land use practices, does not reflect methodological advancements in terms of assessments and monitoring that integrate local communities’ knowledge with ecological methods. In this paper, we evaluated the efficacy of three different methods related to herder assessments and monitoring of land degradation; herder knowledge and ecological methods of assessing impacts of livestock grazing along gradients of land use from settlement and joint monitoring of selected marked transects to understand long-term vegetation changes in southwestern Marsabit northern Kenya. The performance of each method was carefully evaluated and interpreted in terms of the indicators used by herders and ecologists. Herder interpretations were then related to ecologists’ empirical analysis of land degradation. The Rendille nomads have a complex understanding of land degradation which combines environmental and livestock productivity indicators, compared to conventional scientific approaches that use plant-based indicators alone. According to the herders, the grazing preference of various livestock species (e.g., grazers versus browsers) influences perceptions of land degradation, suggesting degradation is a relative term. The herders distinguished short-term changes in vegetation cover from long-term changes associated with over-exploitation. They attributed current environmental degradation around pastoral camps, which shift land use between the alternating wet and dry seasons, to year-round grazing. We deduced from long-term observation that herders interpret vegetation changes in terms of rainfall variability, utilitarian values and intensification of land use. Long-term empirical data (23 years) from repeated sampling corroborated herder interpretations. Land degradation was mostly expressed in terms of declines in woody plant species, while spatial and temporal dynamics of herbaceous species reflected the effects of seasonality. The efficacy of the three methods were inferred using explanatory strengths of ecological theory; insightfulness of the methods for describing land degradation and the likelihood of using the methods for promoting local community participation in the implementation of the UN Convention on Combating Desertification (CCD) and the Convention on Biological Diversity (CBD).