Cancer chemotherapy and somatic cell mutation

The occurrence of a second neoplasm is one of the major obstacles in cancer chemotherapy. The elucidation of the genotoxic effects induced by anti-cancer drugs is considered to be helpful in identifying the degree of cancer risk. Numerous investigations on cancer patients after chemotherapy have demonstrated: (i) an increase in the in vivo somatic cell mutant frequency (Mf) at three genetic loci, including hypoxanthine–guanine phosphoribosyl-transferase (hprt), glycophorin A (GPA), and the T-cell receptor (TCR), and (ii) alterations in the mutational spectra of hprt mutants. However, the time required for and the degree of such changes are quite variable among patients even if they have received the same chemotherapy, suggesting the existence of underlying genetic factor(s). Accordingly, some cancer patients prior to chemotherapy as well as patients with cancer-prone syndrome have been found to show an elevated Mf. Based on the information obtained from somatic cell mutation assays, an individualized chemotherapy should be considered in order to minimize the risk of a second neoplasm.     

Effect of low ambient temperature on protein turnover and heat production in chicks

1. Effect of low ambient temperature on protein turnover in the liver and whole body was investigated in chicks together with the contribution of protein synthesis to the total heat production. 2. Both protein synthesis and degradation in the whole body were increased, the latter to a larger extent, at low ambient temperature (LT, 22 degrees C) compared with adequate temperature (AT, 30 degrees C). Liver protein synthesis was not significantly altered by the temperature treatment. 3. The total heat production of LT group was as high as 160% of the AT group. 4. The increased heat production due to enhanced whole-body protein synthesis accounted for only 1.4% of the heat increment in thermogenesis at low ambient temperature, suggesting that protein synthesis would contribute little, if any, to cold-induced thermogenesis in chicks.     

Induction of migration of periodontal ligament cells by selective regulation of integrin subunits

The recruitment of tissue‐resident stem cells is important for wound regeneration. Periodontal ligament cells (PDL cells) are heterogeneous cell populations with stemness features that migrate into wound sites to regenerate periodontal fibres and neighbouring hard tissues. Cell migration is regulated by the local microenvironment, coordinated by growth factors and the extracellular matrix (ECM). Integrin‐mediated cell adhesion to the ECM provides essential signals for migration. We hypothesized that PDL cell migration could be enhanced by selective expression of integrins. The migration of primary cultured PDL cells was induced by platelet‐derived growth factor‐BB (PDGF‐BB). The effects of blocking specific integrins on migration and ECM adhesion were investigated based on the integrin expression profiles observed during migration. Up‐regulation of integrins α3, α5, and fibronectin was identified at distinct localizations in migrating PDL cells. Treatment with anti‐integrin α5 antibodies inhibited PDL cell migration. Treatment with anti‐integrin α3, α3‐blocking peptide, and α3 siRNA significantly enhanced cell migration, comparable to treatment with PDGF‐BB. Furthermore, integrin α3 inhibition preferentially enhanced adhesion to fibronectin via integrin α5. These findings indicate that PDL cell migration is reciprocally regulated by integrin α3‐mediated inhibition and α5‐mediated promotion. Thus, targeting integrin expression is a possible therapeutic strategy for periodontal regeneration.     

Relationship between adult height and body weight and risk of carotid atherosclerosis assessed in terms of carotid intima-media thickness: The Nagasaki Islands study

Background

Previous studies have reported an inverse association between height and risk of cardiovascular disease. However, evidence is limited for the association between risk of atherosclerosis and height. Further, although the association between atherosclerosis and body mass index (BMI) is reportedly positive, there have been no reports of studies on associations between height and atherosclerosis in relation to BMI.

Methods

We conducted a cross-sectional study of Japanese men aged 30 to 89 years undergoing general health check-ups.

Results

Of the 1,337 men, 312 were diagnosed with carotid atherosclerosis (carotid intima-media thickness (CIMT) ≥ 1.1 mm), but no significant association was found between height and carotid atherosclerosis for the entire study group. Stratification by BMI status of those analytical findings disclosed a significant inverse association between height and carotid atherosclerosis among overweight (BMI ≥ 25 kg/m²) but not among non-overweight (BMI < 25 kg/m²) men. The classical cardiovascular risk factors-adjusted odds ratio (OR) and 95% confidence interval (CI) of carotid atherosclerosis for an increment of one SD (standard deviation) in height (6.70 cm) were 0.71 (0.54 to 0.94) for overweight (BMI ≥ 25 kg/m²) and 1.05 (0.87 to 1.27) for non-overweight (BMI < 25 kg/m²) men.

Conclusion

Independent from classical cardiovascular risk factors, height was found to be inversely associated with carotid atherosclerosis for overweight but not for non-overweight men.     

Evaluation of high sensitive C-reactive protein and 5-10 methylenetetrahydrofolate reductase genotype in Japanese young adults

Primary objective: To carry out a preliminary evaluation of subclinical inflammation and its genetic background in young adults.

Research design: Fifty-five healthy Japanese young adults aged 19–27 years (37 males and 18 females, mean age: 22.3 years), and 58 healthy Japanese adults aged 40 to 60 years (21 males and 37 females, mean age: 51.5 years) were included in this study.

Methods and procedures: We measured plasma high-sensitive C-reactive protein (hs-CRP) levels and screened for the C677T polymorphism of the 5-10 methylenetetrahydrofolate reductase gene (MTHFR), which is considered a genetic risk factor for atherosclerosis, by HinfI digestion.

Main outcomes and results: Hs-CRP levels of the young adult group were significantly lower than the levels of the middle aged group (0.014±0.030 mg/dl vs. 0.031±0.040 mg/dl, p=0.005). The levels were significantly higher in males than in females (0.028±0.019 mg/dl vs. 0.013±0.010 mg/dl, p=0.008) among young adults. Furthermore, we evaluated the relationship of the C677T genotype and hs-CRP values, but found no association between them.

Conclusions: Although the sample size is limited, our preliminary study demonstrated the profiles of hs-CRP in Japanese young adults. Further investigation will be needed to establish the guidelines for customized school health education using sensitive laboratory and genetic markers.