Effects of BCG (Bacillus Calmette–Guérin) Vaccines on Immune Responses in Mice

The effects of killed and living BCG on antibody production against hamster erythrocytes (HRBC) and the 2, 4, 6-trinitrophenyl (TNP) group were studied in SL mice. Killed and living BCG, each in doses of 0.008 mg, 0.08 mg, 0.8 mg and 8 mg per mouse, were intravenously inoculated 7 days prior to primary immunization with HRBC. Secondary immunization was carried out 28 days later with TNP-HRBC. Anti-HRBC and anti-TNP antibodies were estimated by a hemagglutination test. The results showed that pretreatment with killed or living BCG enhanced the antibody production against both HRBC and TNP. Comparing the effects of these two BCG preparations, it was noted that killed BCG augmented the anti-HRBC antibody production more effectively than living BCG. In regard to the anti-TNP antibody production, living BCG exhibited a greater augmenting effect than killed BCG. This difference in the modes of action of killed and living BCG was remarkable when two groups given 8 mg of killed and living BCG were compared. In addition, it was shown that living BCG at a dose as high as 8 mg was able to augment the anti-TNP antibody production, even in the absence of preceding immunization with HRBC.     

Mechanism of methylmercury release from bound type in bloodstream or tissues.

Reductants involving selenite freed methylmercury from bound protein without breaking the mercury-carbon bond in conjunction with sulfhydryls such as cysteine or homocysteine. The free methylmercury was transfered through an organic layer from the original -SH radicals to the other -SH radicals. The same effect occurred in normal physical reactions resulting from oxidoreductases, alcohol or lactic dehydrogenase. The oxidation-reduction system may play an important role in transfer of methylmercury from blood to tissues, or vice versa.     

An alkaline metallo-proteinase in the human uterine cervix an changes in its activity by cervical ripening

Human uterine cervix at term pregnancy was found to contain an alkaline metallo-proteinase by use of a synthetic substrate, 2,4-dinitrophenyl-L-Pro-L-Gln-Gly-L-Ile-L-Ala-Gly-L-Gln-D-Arg. The enzyme (with a molecular weight of 3.8 . 10(4)) was most active around pH 9.2 toward casein and N alpha-benzoyl-DL-Arg-rho-nitroanilide. [14C]-Gelatin and proteoglycan subunit were also substrates for the enzyme, but [14C]collagen was not. In particular, the enzyme digested gelatin 70-times faster than the novel neutral proteinase in the cervix. Although EDTA was a potent inhibitor, 1,10-phenanthroline, human serum, diisopropylfluorophosphate and elastatinal had no effect on the enzyme. Alkaline proteinase in term pregnant cervices was significantly higher than in non-pregnant ones.     

Planting geometry as a pre‐screening technique for identifying CO2 responsive rice genotypes: a case study of panicle number

Identifying CO₂ responsive genotypes is a major target for enhancing crop productivity under future global elevated atmospheric CO₂ concentration ([CO₂]). However, [CO₂]‐fumigation facilities are extremely expensive and are not easily accessible, and are limited in space for large‐scale screening. Hence, reliable donors for initiating [CO₂]‐responsive breeding programs are not in place for crops, including rice. We propose a simple and novel phenotyping method for identifying [CO₂]‐responsive genotypes, and quantify the responsiveness to low planting density over 4‐year trials across both temperate and tropical conditions. Panicle number per plant is the key determinant of grain yield and hence was the focus trait across all our trials. In temperate climate, a 3‐season field screening using 127 diverse rice genotypes and employing two planting densities (normal and low density) was conducted. Two japonica genotypes were selected based on their higher responsiveness to low planting density as candidates for validating the proposed phenotyping protocol as a pre‐screen for [CO₂]‐responsiveness. The approach using the two selected candidates and three standard genotypes was confirmed using a free‐air CO₂ enrichment facility and temperature gradient chambers under elevated [CO₂]. In tropical climate, we grew three rice cultivars, previously identified for their [CO₂]‐responsiveness, at two planting densities. The experiments provided confirmation that responsiveness to low planting density was correlated with that of [CO₂]‐responsiveness across both the temperate and tropical conditions. The planting density would be useful pre‐screening method for testing large panels of diverse germplasm at low cost complemented by available CO₂‐control facilities for final validation of candidates from the pre‐screens.     

Effect of candesartan monotherapy on lipid metabolism in patients with hypertension: a retrospective longitudinal survey using data from electronic medical records

Background

Studies focusing on the add-on effects of angiotensin II type 1 receptor blockers (ARBs) other than their antihypertensive effect are receiving attention. However, the effects of prolonged administration of ARBs on lipid metabolism in clinical cases are unclear. Our aims were to survey the changes in plasma lipid profile in patients with hypertension over a one-year period, and to examine the correlations between these values and the time after the start of ARB monotherapy with candesartan.

Methods

We carried out candesartan monotherapy in patients with mild to moderate hypertension and examined the longitudinal changes in plasma lipid profile. Data from 405 patients for triglyceride (TG), 440 for total cholesterol (TC), 313 for high density lipoprotein cholesterol (HDL-C) and 304 for low density lipoprotein cholesterol (LDL-C) were obtained from the electronic medical records (EMRs) in the Clinical Data Warehouse (CDW) of Nihon University School of Medicine (NUSM). The inverse probability of treatment weighting (IPTW) method (calculated from the inverse of the propensity score) was used to balance the covariates and reduce bias in each treatment duration. Linear mixed effects models were used to analyse the relationship between these longitudinal data of blood examinations and covariates of patient sex, age, diagnosis of diabetes mellitus (DM) and duration of candesartan monotherapy.

Results

Plasma HDL-C level was associated with sex, duration of treatment, and interaction of sex and treatment duration, but not with age or diagnosis of DM. HDL-C level was significantly decreased during the 6~9 months period (p = 0.0218) compared with baseline. TG and TC levels were associated with sex, but not with age, diagnosis of DM or treatment duration. LDL-C level was not associated with any covariate. Analysis of the subjects divided by sex revealed a decrease in HDL-C in female subjects (during the 6~9 months period: p = 0.0054), but not in male subjects.

Conclusions

Our study revealed that administration of candesartan slightly decreased HDL-C in female subjects. However, TG, TC and LDL-C levels were not influenced by candesartan monotherapy. Candesartan may be safely used for patients with hypertension with respect to lipid metabolism, because the effect of candesartan on lipids may be small.

     

Effects of administration of transforming growth factor (TGF)-beta1 and anti-TGF-beta1 antibody on the mechanical properties of the stress-shielded patellar tendon

Previous studies have shown that, in the stress-shielded patellar tendon, the mechanical properties of the tendon were dramatically reduced and TGF-beta was over-expressed in tendon fibroblasts. In the present study, therefore, we tested two supportive hypotheses using 40 rabbits: One was that an application of TGF-beta1 might significantly increase the tensile strength and the tangent modulus of the stress-shielded patellar tendon. The other one was that an administration of anti-TGF-beta1 antibody might significantly reduce the mechanical properties of the stress-shielded patellar tendon. In the results, an application of 4-ng TGF-beta1 significantly increased the tangent modulus of the stress-shielded patellar tendon at 3 weeks (p = 0.019), compared with the sham treatment. Concerning the tensile strength, the 4-ng TGF-beta1 application increased the average value, but a statistical significance was not reached. An application of 50-microg anti-TGF-beta1 antibody significantly reduced the tangent modulus and the tensile strength of the stress-shielded patellar tendon at 3 weeks (p = 0.0068 and p = 0.0355), compared with the sham treatment. Because the stress-shielding treatment used in this study dramatically reduces the tangent modulus and the tensile strength of the patellar tendon, the present study suggested that an administration of TGF-beta1 weakly but significantly inhibited the reduction of the mechanical properties of the stress-shielded patellar tendon, and that inactivation of TGF-beta1 with its antibody significantly enhanced the reduction of the mechanical properties that occurs in the stress-shielded patellar tendon. These results suggested that TGF-beta1 plays an important role in remodeling of the stress-shielded patellar tendon.     

Live-cell imaging reveals replication of individual replicons in eukaryotic replication factories

Faithful DNA replication ensures genetic integrity in eukaryotic cells, but it is still obscure how replication is organized in space and time within the nucleus. Using timelapse microscopy, we have developed a new assay to analyze the dynamics of DNA replication both spatially and temporally in individual Saccharomyces cerevisiae cells. This allowed us to visualize replication factories, nuclear foci consisting of replication proteins where the bulk of DNA synthesis occurs. We show that the formation of replication factories is a consequence of DNA replication itself. Our analyses of replication at specific DNA sequences support a long-standing hypothesis that sister replication forks generated from the same origin stay associated with each other within a replication factory while the entire replicon is replicated. This assay system allows replication to be studied at extremely high temporal resolution in individual cells, thereby opening a window into how replication dynamics vary from cell to cell.     

Metal ion-directed cooperative DNA binding of small molecules

Compound (1), which consists of an oxine and a pyridinium group, was synthesized as a metal-responsive DNA binding ligand. Two 1s coordinate to a Cu(II) to form a stable dimer (1(2)-Cu), even in the presence of DNA. The binding of 1 with sonicated calf thymus DNA was enhanced by ca. 10(3) times after forming the dimer; the binding constants were estimated to be 3.2 x 10(4)M(-1) and 2.4 x 10(7)M(-1) in the absence and the presence, respectively, of a half mole of Cu(II). The enormous acceleration of the binding is partly attributed to the generation of a dicationic charge by the formation of the dimer. High cooperativity between dimers could be also responsible; dimers would gather along the duplex as a template to form 1D spiral aggregates.