Functional involvement of endogenous anxiogenic neuropeptide in brains]

Neuronal GABA(A)/benzodiazepine and monoamine receptors participate in anxiety. Diazepam binding inhibitor (DBI), an endogenous anxiogenic neuropeptide, significantly increases in brains only after treatment with psychological stress, and this increase is completely abolished by benzodiazepines. Therefore, it is through that DBI may be involved in anxiogenesis produced by psychological stress. Furthermore, increases in cerebral DBI are observed in patients with several disorders accompanying anxiety and fear, which suggest that cerebral DBI may be an essential factor for anxiogenesis, and that it may be, at least in part, a biological index to evalulate anxiety.     

Progressive outer retinal necrosis in a patient with nephrotic syndrome

Progressive outer retinal necrosis syndrome (PORN) is a variant of necrotizing herpetic retinopathy and the majority of the described cases were related to acquired immunodeficiency syndrome. We present a patient who is HIV negative with nephrotic syndrome and prednisolone use for 4 months who showed clinical features of PORN. Low CD4 counts and lymphocytopenia suggested immunosuppression. In the left eye, tractional retinal detachment at the posterior pole followed by incomplete posterior vitreous detachment developed. In addition to intravenous administration of acyclovir, vitreous surgeries including stripping of the posterior hyaloid and silicone-oil tamponade were successfully performed to repair the retinal detachment in the left eye and to prevent it in the right eye.     

IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells

Neurokinin 2 receptor (NK2R), a G protein‐coupled receptor for neurokinin A (NKA), a tachykinin family member, regulates various physiological functions including pain response, relaxation of smooth muscle, dilation of blood vessels, and vascular permeability. However, the precise role and regulation of NK2R expression in cancer cells have not been fully elucidated. In this study, we found that high NK2R gene expression was correlated with the poor survival of colorectal cancer patients, and Interferon (IFN‐α/β) stimulation significantly enhanced NK2R gene expression level of colon cancer cells in a Janus kinas 1/2 (JAK 1/2)‐dependent manner. NKA stimulation augmented viability/proliferation and phosphorylation of Extracellular‐signal‐regulated kinase 1/2 (ERK1/2) levels of IFN‐α/β‐treated colon cancer cells and NK2R blockade by using a selective antagonist reduced the proliferation in vitro. Administration of an NK2R antagonist alone or combined with polyinosinic‐polycytidylic acid, a synthetic analog of double‐stranded RNA, to CT26‐bearing mice significantly suppressed tumorigenesis. NK2R‐overexpressing CT26 cells showed enhanced tumorigenesis and metastatic colonization in both lung and liver after the inoculation into mice. These findings indicate that IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells, suggesting that NK2R blockade may be a promising strategy for colon cancers.     

A tumor metastasis‐associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity

Although neoantigens are one of the most favorable targets in cancer immunotherapy, it is less versatile and costly to apply neoantigen‐derived cancer vaccines to patients due to individual variation. It is, therefore, important to find highly immunogenic antigens between tumor‐specific or associated antigens that are shared among patients. Considering the cancer immunoediting theory, immunogenic tumor cells cannot survive in the early phase of tumor progression including two processes: elimination and equilibrium. We hypothesized that highly immunogenic molecules are allowed to be expressed in tumor cells after an immune suppressive tumor microenvironment was established, if these molecules contribute to tumor survival. In the current study, we focused on TWIST1 as a candidate for highly immunogenic antigens because it is upregulated in tumor cells under hypoxia and promotes tumor metastasis, which is observed in the late phase of tumor progression. We demonstrated that TWIST1 had an immunogenic peptide sequence TWIST1_140–162, which effectively activated TWIST1‐specific CD4⁺ T‐cells. In a short‐term culture system, we detected more TWIST1‐specific responses in breast cancer patients compared with in healthy donors. Vaccination with the TWIST1 peptide also showed efficient expansion of TWIST1‐reactive HTLs in humanized mice. These findings indicate that TWIST1 is a highly immunogenic shared antigen and a favorable target for cancer immunotherapy.     

Mediastinal Cystic Parathyroid Adenoma Diagnosed by Somatostatin Receptor Scintigraphy

A 71-year-old man complained of nausea and loss of appetite for eight months prior to admission. He was transported to a hospital with disorientation and diagnosed with primary hyperparathyroidism by laboratory examinations. However, ultrasonography, computed tomography, and technetium-99m labeled methoxyisobutyl isonitrile (^99mTc-MIBI) with single-photon emission computed tomography did not yield definite results. In contrast, somatostatin receptor scintigraphy successfully identified the lesion responsible for the over-secretion of parathyroid hormone within the middle mediastinum. The tumor was successfully resected by surgery, and a histopathological analysis confirmed the parathyroid adenoma nature of the tumor.     

Gene Expression Analysis Using a High‐Resolution DNA Microarray of Peripheral Whole Blood Immediately Before and After Leukocytapheresis for Rheumatoid Arthritis

Leukocytapheresis (LCAP) is a safe, unique therapy pertaining to intractable rheumatoid arthritis (RA) even in cases of drug allergy or infectious states. To investigate how to represent LCAP efficacy, we have conducted gene expression analyses from the peripheral blood of RA patients treated with non‐woven polyethylene terephthalate filters. Peripheral blood samples were collected immediately before and after treatment from eight RA patients who received LCAP. Among these patients, all of them achieved 20% improvement in the core set of the American College of Rheumatology (ACR20), and thus, they were confirmed as LCAP responders. Gene expression analysis was done with a high‐resolution DNA microarray. The results of each of the two groups' gene expression values (immediately before and after LCAP) were calculated using Welch's t‐test. Calculations were performed with a statistical software R.basic package: if the P‐value was less than 0.05, this was seen as a significant change. In a comparison of 25 370 gene expressions, the number of genes showing a P‐value < 0.05 in the upregulating group was 2110, and in the downregulating group it was 1864. The results of pathway analysis using the MetaCore program indicate that gene groups work for cytoskeletal remodeling are upregulated, and genes related to immune responses, such as antigens presenting via major histocompatibility complex class I and II, are downregulated just after LCAP. These findings may relate to LCAP efficacy for RA patients, but this needs further investigation.     

An Analytical Model / Emotional Intelligence Quotient and QOL in Mothers with Infants in Japan

Objective: The purpose of this study was to examine the relationship between the emotional intelligence quotient and health-related quality of life using structural equation modeling.Methods: A self-administered questionnaire survey was conducted among 1,911 mothers who visited the Health Center for an infant medical examination. A hypothetical model was constructed using variables of the emotional intelligence quotient, social support, coping, parenting stress, and perceived health competence.Result: There were a total of 1,104 valid responses (57.8%). Significant standardized estimates were obtained, confirming the goodness of fit issues with the model. The emotional intelligence quotient had a strong impact on physical and psychological quality of life, and showed the greatest association with coping. This study differed from previous studies in that, due to the inclusion of social support and explanatory variables in coping, an increase in coping strategies was more highly associated with emotional intelligence quotient levels than with social support.Conclusion: An enhanced emotional intelligence quotient should be considered a primary objective to promote the health of mothers with infant children.