Anti-tumor effects of mAb against L-type amino acid transporter 1 (LAT1) bound to human and monkey LAT1 with dual avidity modes.

L-Type amino acid transporter 1 (LAT1) disulfide linked to CD98 heavy chain (hc) is highly expressed in most cancer cells, but weakly expressed in normal cells. In the present study, we developed novel anti-LAT1 mAbs and showed internalization activity, inhibitory effects of amino acid uptake and cell growth and antibody-dependent cellular cytotoxicity, as well as in vivo antitumor effects in athymic mice. Furthermore, we examined the reactivity of mAbs with LAT1 of Macaca fascicularis to evaluate possible side-effects of antihuman LAT1 mAbs in clinical trials. Antihuman LAT1 mAbs reacted with ACHN human and MK.P3 macaca kidney-derived cells, and this reactivity was significantly decreased by siRNAs against LAT1. Macaca LAT1 cDNA was cloned from MK.P3, and only two amino acid differences between human and macaca LAT1 were seen. RH7777 rat hepatoma and HEK293 human embryonic kidney cells expressing macaca LAT1 were established as stable transfectants, and antihuman LAT1 mAbs were equivalently reactive against transfectants expressing human or macaca LAT1. Dual (high and low) avidity modes were detected in transfectants expressing macaca LAT1, MK.P3, ACHN and HCT116 human colon cancer cells, and KA values were increased by anti-CD98hc mAb, suggesting anti-LAT1 mAbs detect an epitope on LAT1-CD98hc complexes on the cell surface. Based on these results, LAT1 may be a promising anticancer target and Macaca fascicularis can be used in preclinical studies with antihuman LAT1 mAbs.

[A case of adult-onset type II citrullinemia in an elderly patient].

A 72-year-old man presented with consciousness disturbance. The results of brain magnetic resonance imaging and cerebrospinal fluid examination were normal, but triphasic waves were noted on electroencephalography. His plasma ammonia level was elevated due to which encephalopathy secondary to hyperammonemia was suspected. However, his liver function was normal, and no evidence of cirrhosis or portal-systemic shunt was noted. The patient's medical history revealed that he had a tendency to excessively consume pulse products since childhood, and an amino acid analysis showed elevation of citrulline and arginine levels. Thus, we diagnosed the patient with an extremely rare case of adult-onset type II citrullinemia, which was triggered by cessation of the intake of pulse foods (soybeans and peanuts) due to dental problems.

[Association between health literacy and behavior regarding health checkups and health counseling in Japanese employees: A comprehensive health literacy survey of a Japanese railway company].

BACKGROUND: Globally, health literacy is considered important for healthy ageing. However, to our knowledge, no study has investigated comprehensive health literacy in Japanese employees. OBJECTIVE: This study aimed to examine comprehensive health literacy in employees of company A, a Japanese railway company, and to determine the association between health literacy and behavior regarding health checkups and health counseling in the employees. METHODS: A representative sample of company A with 541 employees was selected through random sampling. We divided the sample into 20 groups based on gender, age, night shift work, and administrative position. These groups were compared with the employee distribution of company A. The self-administered Japanese version of the 47-item European Health Literacy Survey Questionnaire was distributed to the participants via mail from May 1, 2017, to May 30, 2017. This questionnaire consists of three domains, each with its own index: health care health literacy (health care health literacy index [HC-HL]), disease prevention health literacy (disease prevention health literacy index [DP-HL]), and health promotion health literacy (health promotion health literacy index [HP-HL]). Additionally, general health literacy (general health literacy index [GEN-HL]) was also assessed. Statistical analyses were performed to identify the association between health literacy and behavior regarding health checkups and health counseling in the employees in company A. Furthermore, we compared the health literacy of the present sample with that of samples in past studies by Nakayama et al. (2015) and Goto et al. (2018). RESULTS: A total of 417 questionnaires were returned. The health literacy scores were calculated based on the valid responses of 381 participants. The mean health literacy scores in company A for GEN-HL, HC-HL, DP-HL, and HP-HL were 25.1, 24.6, 27.9, and 22.8, respectively. The mean health literacy scores in the survey by Nakayama et al. for GEN-HL, HC-HL, DP-HL, and HP-HL were 25.3, 25.7, 22.7, and 25.5, respectively, and those in the survey by Goto et al. were 29.79, 29.23, 32.52, and 27.60, respectively. There was no significant difference between participant characteristics and GEN-HL scores. In contrast, there was a significant difference in the association between GEN-HL and health counseling in terms of the number of times health counseling was provided in the workplace. However, there was no significant difference between those who did not wish to receive health counseling and GEN -HL scores. CONCLUSION: The health literacy in railway company A was low. The results of this study and those of past studies did not demonstrate similar trends for health literacy. Additionally, GEN-HL scores were likely to increase if the number of people who wished to receive health counseling increased.