Isolation and characterization of 25 polymorphic microsatellites of the large Japanese wood mouse (Apodemus speciosus)

The large Japanese wood mouse (Apodemus speciosus) is common, but endemic to Japan, and its population structure was affected by habitat fragmentation because of urbanization. It suggested that the species might be one of the important models for the conservation of ecosystems and biodiversity affected by humans, including the effect of radioactive discharge caused by nuclear power plant accidents at Fukushima. We developed and characterized 25 novel polymorphic microsatellite markers from the next-generation sequencing data in an effort to provide an effective tool for genetic studies on this species. In 8 individuals from Aomori, Japan, the number of alleles and expected heterozygosities ranged from 5 to 13 and from 0.795 to 0.991, respectively, suggesting the availability of these markers for genetic studies in this species.     

Chemoradiotherapy for patients with recurrent lymph-node metastasis or local recurrence of gastric cancer after curative gastrectomy

Objectives

Whether chemoradiotherapy (CRT) is clinically beneficial for the management of postoperative recurrence of advanced gastric cancer remains unclear. We retrospectively studied treatment outcomes in patients who had unresectable localized recurrence after surgery for advanced gastric cancer and evaluated the safety and efficacy of CRT.

Methods

The study group comprised 21 patients who received concurrent CRT for unresectable localized recurrence after undergoing R0 resection for stage II/III advanced gastric cancer. Localized recurrence was defined as a few or limited recurrent lesions.

Results

The recurrence pattern was anastomotic recurrence in 7 patients, abdominal lymph-node recurrence in 12, and anastomotic recurrence plus abdominal lymph-node recurrence in 2. The median total dose of radiotherapy was 48.6 Gy (range 39.6–56.0), and the CRT completion rate was 100 % (21 of 21 patients). CRT-related grade 3 or higher toxicity comprised neutropenia in 33.3 % of patients and anorexia in 9.5 %. The response rate was 61.9 % (complete response 38.1 %, partial response 23.8 %). The median overall survival was 35.0 months.

Conclusions

We conclude that CRT may become one treatment strategy for the management of unresectable localized recurrence after curative resection of advanced gastric cancer.

     

Strategy for affinity maturation of an antibody with high evolvability to (4-hydroxy-3-nitrophenyl) acetyl hapten

In order to quantitate the contribution of amino acid replacements to an increase in affinity during affinity maturation, we measured thermodynamic parameters of the antigen-antibody interaction for a group of anti-(4-hydroxy-3-nitrophenyl) acetyl monoclonal antibodies whose differences in amino acid sequences had arisen only from somatic hypermutation. We prepared a common ancestor and hypothetical intermediate clones that might occur on the affinity maturation pathway, by employing site-directed mutagenesis. Isothermal calorimetric titration of the antigen-antibody reaction revealed that antibody evolution proceeds in two steps. The first step is driven by a decrease in enthalpy, in which two amino acid replacements in the VL region play an essential role. Further accumulation of amino acid replacements in VH and VL regions during the second step induce a progressive increase in affinity, which is driven by an increase in entropy, which has a cooperative mutational effect.     

Background factors of chemical intolerance and parent–child relationships

Background

Chemical intolerance is a widespread public health problem characterized by symptoms that reportedly result from low-level exposure to chemicals. Although several studies have reported factors related to chemical intolerance in adults, the impact of family members has not been reported. In the present study, we investigated the background factors related to chemical intolerance in family members and parent–child relationships.

Methods

We distributed a self-reported questionnaire to 4325 mothers who were invited to visit the Kishiwada Health Center in Kishiwada City, Osaka, between January 2006 and December 2007 for the regular health checkup of their three-and-a-half-year-old children.

Results

The prevalence of chemical intolerance in the 3-year-old children was almost one eighteenth of that reported by their mothers. Multiple logistic regression analyses revealed that cold sensitivity [odds ratio (OR), 1.89; 95% confidence interval (CI), 1.04–3.44], past bronchial asthma (OR, 2.84; 95% CI, 1.46–5.53), and any past allergies (OR, 2.21; 95% CI, 1.36–3.60) were significantly associated with chemical intolerance in the mother. The presence of indoor cat during childhood (OR, 1.99; 95% CI, 1.08–3.69) was significantly associated with chemical intolerance in the mother; however, the association was weak compared with cold sensitivity and past asthma and allergies. The current chemical intolerance of the mother was significantly associated with allergic rhinitis (OR, 2.32; 95% CI, 1.19–4.53), bronchial asthma (OR, 3.66; 95% CI, 2.00–6.69), and chronic bronchitis (OR, 3.69; 95% CI, 1.04–13.03) in her 3-year-old child.

Conclusions

The results suggest that inherent physical constitution and childhood housing environment are associated with a risk of acquiring chemical intolerance. Children of mothers with chemical intolerance have a possible risk of respiratory hypersensitivity or inflammation. Further investigation is recommended to determine the inherent physical constitution and background environmental factors associated with the risk of acquiring chemical intolerance. The impact of having mothers with chemical intolerance on the health of children also requires further study.

     

Survey on changes in subjective symptoms,onset/trigger factors,allergic diseases,and chemical exposures in the past decade of Japanese patients with multiple chemical sensitivity

Background

Recently, with rapid changes in the Japanese lifestyle, the clinical condition of patients with multiple chemical sensitivity (MCS) may also have undergone change. Thus, we conducted a new survey for subjective symptoms, ongoing chemical exposures, the prevalence of allergic diseases, and presumed onset/trigger factors in patients with MCS and compared results with those of an old survey from ten years ago.

Altered Cerebellum Development and Dopamine Distribution in a Rat Genetic Model with Congenital Hypothyroidism

Thyroid hormones play crucial roles in the development and functional maintenance of the central nervous system. Despite extensive studies of the neural function of thyroid hormones, little is known about the effects of hypothyroidism on behavioural traits and the mechanisms underlying such effects. In the present study, we report an investigation of congenitally hypothyroid mutant rdw rats, revealing a novel function of thyroid hormones in the central nervous system. The rdw rats were subjected to behavioural analyses such as the rotarod test, open field test and circadian activity measurement. To determine the cause of behavioural disorders, cerebellar morphogenesis was examined by immunohistochemical analysis, and the axonal transport of dopamine in the nigrostriatal pathway was analysed by high‐performance liquid chromatography and western blotting. The effects of thyroxine administration to the rdw rats were examined by behavioural analysis. The rdw rats showed severe impairment of motor coordination and balance. This could be explained by the fact that the rats showed severe retardation of cerebellar morphogenesis, which correlates with the small somata and poor dendritic arborisation of Purkinje cells and retarded migration of granule cells particularly during the first two postnatal weeks. Moreover, the rdw rats showed hypoactivity, characterised by decreased circadian locomotor activity. After weaning, thyroxine administration improved the dwarfism in rdw rats but had no effect on cerebellar function. In addition, the rdw rats showed anxiety and depression intrinsically to novel surroundings. Interestingly, the rdw rats showed high levels of dopamine in the substantia nigra and low levels in the striatum, an important centre for the coordination of behaviour. Furthermore, low levels of tubulin in the striatum were detected, indicating the aberrant axonal transport of dopamine in the nigrostriatal pathway as a result of the reduced delivery of microtubules. These findings indicate an important function of thyroid hormones in cerebellar formation and in the regulation of axonal transport of dopamine. Moreover, rdw rats will be useful for studies of brain function and behavioural disorders in congenital hypothyroidism.