Depression and anxiety symptoms among Vietnamese migrants in Japan during the COVID-19 pandemic.

This study aimed to examine the mental health status and related factors among Vietnamese migrants in Japan during the COVID-19 pandemic. We conducted an online cross-sectional survey between September 21 and October 21, 2021. Along with Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item (GAD-7) scores, we collected data on demographics, changes in socioeconomic status due to the pandemic, language proficiency, social support, and health conditions. Multivariate logistic regression was performed to identify factors related to symptoms of depression and anxiety. Among 621 participants who completed the questionnaire, moderate-to-severe symptoms of depression (PHQ-9 score ≥ 10 points) and mild-to-severe symptoms of anxiety (GAD-7 score ≥ 5 points) were observed in 203 (32.7%) and 285 (45.9%) individuals, respectively. Factors related to depressive symptoms were age (95% confidence interval [CI]=0.89-0.99), pre-existing health conditions (95% [CI]=1.61-3.76), and a low subjective socioeconomic status (95% [CI]=1.64-3.71). Factors related to anxiety symptoms were being single (95% [CI]=1.01-2.93), having pre-existing health conditions (95% [CI]=1.63-3.88), subjective socioeconomic status (95% [CI]=1.87-3.97), and absence of a partner to discuss one's health with (95% [CI]=1.11-2.47). Vietnamese migrants in Japan experienced a decrease in income, worsening working conditions, and poor mental health status during the COVID-19 pandemic. Further investigations are necessary to find an effective way to increase their social support and mitigate socioeconomic adversities.

Efficacy, Immunogenicity, and Safety of COVID-19 Vaccines in Patients with Autoimmune Diseases: A Systematic Review and Meta-Analysis.

Patients with autoimmune diseases are among the susceptible groups to COVID-19 infection because of the complexity of their conditions and the side effects of the immunosuppressive drugs used to treat them. They might show impaired immunogenicity to COVID-19 vaccines and have a higher risk of developing COVID-19. Using a systematic review and meta-analysis, this research sought to summarize the evidence on COVID-19 vaccine efficacy, immunogenicity, and safety in patients with autoimmune diseases following predefined eligibility criteria. Research articles were obtained from an initial search up to 26 September 2022 from PubMed, Embase, EBSCOhost, ProQuest, MedRxiv, bioRxiv, SSRN, EuroPMC, and the Cochrane Center of Randomized Controlled Trials (CCRCT). Of 76 eligible studies obtained, 29, 54, and 38 studies were included in systematic reviews of efficacy, immunogenicity, and safety, respectively, and 6, 18, and 4 studies were included in meta-analyses for efficacy, immunogenicity, and safety, respectively. From the meta-analyses, patients with autoimmune diseases showed more frequent breakthrough COVID-19 infections and lower total antibody (TAb) titers, IgG seroconversion, and neutralizing antibodies after inactivated COVID-19 vaccination compared with healthy controls. They also had more local and systemic adverse events after the first dose of inactivated vaccination compared with healthy controls. After COVID-19 mRNA vaccination, patients with autoimmune diseases had lower TAb titers and IgG seroconversion compared with healthy controls.

A rare case of epithelial-myoepithelial carcinoma ex pleomorphic adenoma of the parotid gland: Radiologic-pathologic correlation.

Carcinoma ex pleomorphic adenoma is a carcinoma that arises from a primary or recurrent benign pleomorphic adenoma. The prevalence of epithelial-myoepithelial carcinoma is low, and this histological type accounting for only 1% of all salivary gland tumors. Here, we report a rare case of Epithelial-Myoepithelial Carcinoma ex pleomorphic adenoma of the parotid gland with a radiologic-pathologic correlation.

Association between glucose tolerance and mortality among Japanese community-dwelling older adults aged over 75 years: 12-year observation of the Tosa Longitudinal Aging Study.

AIM: Although the relationship between impaired glucose tolerance (IGT) and mortality has been investigated in diverse populations, few studies have focused on older populations. This study aimed to investigate the relationship between glucose tolerance and overall mortality among populations aged ≥75 years. METHODS: Data were obtained from the Tosa Longitudinal Aging Study, a community-based cohort survey conducted in Kochi, Japan. According to the results of a 75-g oral glucose tolerance test conducted in 2006, the participants were classified into four categories: normal glucose tolerance (NGT), impaired fasting glucose (IFG)/IGT, newly diagnosed diabetes mellitus (NDM), and known diabetes mellitus (KDM). The primary endpoint was overall mortality. Differences in overall mortality among the four categories were evaluated using the Cox proportional hazards model. RESULTS: During a median of 11.5 years of observation, 125 deaths of the 260 enrolled participants were recorded. The cumulative overall survival rate was 0.52, and the survival rates of NGT, IFG/IGT, NDM, and KDM were 0.48, 0.49, 0.49, and 0.25, respectively (log-rank test, P = 0.139). Adjusted hazard ratios (HRs) for mortality in the IFG/IGT and NDM groups compared with the NGT group were 1.02 (95% confidence interval [CI], 0.66-1.58) and 1.11 (95% CI, 0.56-2.22), while mortality in the KDM group was significantly higher than that in the NGT group (HR, 2.43; 95% CI, 1.35-4.37). CONCLUSION: Mortality did not differ significantly between the IFG/IGT, NDM, and NGT groups, but was higher in the KDM group than in the NGT group. Geriatr Gerontol Int 2023; 23: 341-347.

A cross-sectional survey of material deprivation and suicide-related ideation among Vietnamese technical interns in Japan.

Background: The economic struggles faced by many technical intern trainees in Japan include the necessity to remit money to their home country, debts owed to intermediaries facilitating their arrival, and reduced working hours due to the COVID-19 pandemic. Furthermore, there is concern that the pandemic may contribute to mental instability resulting from the significant life changes experienced by the trainees. This study examined the experience of material deprivation among Vietnamese intern trainees in Japan and explored the correlation between material deprivation and suicidal ideation. Methods: A cross-sectional study was conducted between September and October 2021, involving 310 Vietnamese technical intern trainees. Data from 200 participants were analyzed. The questionnaire included gender, age, duration of residence in Japan, proficiency in the Japanese language, income changes due to the COVID-19 pandemic, material deprivation status, and suicidal ideation. Suicidal ideation was assessed using the ninth item of the Patient Health Questionnaire-9. Logistic regression analysis was performed to investigate the relationship between material deprivation items and suicidal ideation. Results: The mean age of the respondents was 26.0 ± 5.1 years, with 62.0% (n = 124) being male. Among the material deprivation items, 74.0% (n = 148) reported food deprivation, 59.0% (n = 118) reported cellphone bill deprivation, and 55.0% (n = 110) reported medical expense deprivation. Suicidal ideation was reported by 23.0% (n = 46) of the respondents. The prevalence of suicidal ideation was associated with age (p = 0.031, odds ratio [OR] = 0.889, 95% confidence interval [CI] = 0.799-0.990), deprivation of food expenses (p = 0.003, OR = 3.897, 95% CI = 1.597-9.511), and deprivation of cellphone usage (p = 0.021, OR = 3.671, 95% CI = 1.217-11.075). Conclusion: Vietnamese technical intern trainees in Japan faced various forms of material deprivation, which correlated with a high prevalence of significant psychological issues. Suicidal ideation was influenced by factors such as age, deprivation of food expenses, and inability to pay cellphone bills. The experience of material deprivation could have intensified the mental health challenges faced by Vietnamese trainees, particularly in the demanding circumstances of the COVID-19 pandemic.

Perceived risk of infection and death from COVID-19 among community members of low- and middle-income countries: A cross-sectional study.

Background: Risk perceptions of coronavirus disease 2019 (COVID-19) are considered important as they impact community health behaviors. The aim of this study was to determine the perceived risk of infection and death due to COVID-19 and to assess the factors associated with such risk perceptions among community members in low- and middle-income countries (LMICs) in Africa, Asia, and South America. Methods: An online cross-sectional study was conducted in 10 LMICs in Africa, Asia, and South America from February to May 2021. A questionnaire was utilized to assess the perceived risk of infection and death from COVID-19 and its plausible determinants. A logistic regression model was used to identify the factors associated with such risk perceptions. Results: A total of 1,646 responses were included in the analysis of the perceived risk of becoming infected and dying from COVID-19. Our data suggested that 36.4% of participants had a high perceived risk of COVID-19 infection, while only 22.4% had a perceived risk of dying from COVID-19. Being a woman, working in healthcare-related sectors, contracting pulmonary disease, knowing people in the immediate social environment who are or have been infected with COVID-19, as well as seeing or reading about individuals infected with COVID-19 on social media or TV were all associated with a higher perceived risk of becoming infected with COVID-19. In addition, being a woman, elderly, having heart disease and pulmonary disease, knowing people in the immediate social environment who are or have been infected with COVID-19, and seeing or reading about individuals infected with COVID-19 on social media or TV had a higher perceived risk of dying from COVID-19. Conclusions: The perceived risk of infection and death due to COVID-19 are relatively low among respondents; this suggests the need to conduct health campaigns to disseminate knowledge and information on the ongoing pandemic.

Dietary Intake Quality Is Affected by Knowledge and Dietary Intake Frequency among Pregnant Women in Muntinlupa, Philippines: A Cross-Sectional Study.

Improving the nutrition of pregnant women is essential in reducing maternal and child mortality, which is one of the global nutritional goals of 2025. This study evaluated the factors related to the quality of dietary intake among pregnant women in Muntinlupa, Philippines. We conducted a cross-sectional study of 280 pregnant women at a hospital in Muntinlupa from March 2019 to August 2019 using questionnaires. After the primary aggregation, multivariate logistic regression analysis was used to identify factors associated with the quality of dietary intake in pregnant women. Approximately half of the women (46.4%, n = 130) had a low dietary diversity during pregnancy. Less than 30% of the respondents consumed beans, soybean products, and nuts. In the logistic regression analysis, poor maternal knowledge of nutritional sources to prevent anemia (odds ratio (OR) 4.25, 95% confidence interval (CI) 1.47-12.32, p = 0.01) and less frequent meal consumption (OR 2.15, 95% CI 1.08-4.29, p = 0.03) were significantly associated with poor dietary diversity. Our findings are crucial because they suggest that increasing the knowledge of pregnant women about good nutrition and ensuring that dietary intake is frequent and adequate through antenatal care can improve the nutrition of pregnant women.

Relapse prevention group therapy via video-conferencing for substance use disorder: protocol for a multicentre randomised controlled trial in Indonesia.

BACKGROUND: Substance use disorder (SUD) is a leading contributor to the global burden of disease. In Indonesia, the availability of formal treatment for SUD falls short of the targeted coverage. A standardised therapeutic option for SUD with potential for widespread implementation is required, yet evidence-based data in the country are scarce. In this study, we developed a cognitive behavioural therapy (CBT)-based group telemedicine model and will investigate effectiveness and implementability in a multicentre randomised controlled trial. METHODS: A total of 220 participants will be recruited from the social networks of eight sites in Indonesia: three hospitals, two primary healthcare centres and three rehabilitation centres. The intervention arm will participate in a relapse prevention programme called the Indonesia Drug Addiction Relapse Prevention Programme (Indo-DARPP), a newly developed 12-week module based on CBT and motivational interviewing constructed in the Indonesian context. The programme will be delivered by a healthcare provider and a peer counsellor in a group therapy setting via video-conferencing, as a supplement to participants' usual treatments. The control arm will continue treatment as usual. The primary outcome will be the percentage increase in days of abstinence from the primarily used substance in the past 28 days. Secondary outcomes will include addiction severity, quality of life, motivation to change, psychiatric symptoms, cognitive function, coping, and internalised stigma. Assessments will be performed at baseline (week 0), post-treatment (week 13), and 3 and 12 months post-treatment completion (weeks 24 and 60). Retention, participant satisfaction, and cost-effectiveness will be assessed as the implementation outcomes. ETHICS AND DISSEMINATION: The study protocol was reviewed and approved by the Ethics Committees of Universitas Indonesia and Kyoto University. The results will be disseminated via academic journals and international conferences. Depending on trial outcomes, the treatment programme will be advocated for adoption as a formal healthcare-based approach for SUD. TRIAL REGISTRATION NUMBER: UMIN000042186.

BCR/ABL1-positive B-lymphoblastic Lymphoma Successfully Treated with Dasatinib-combined Chemotherapy.

We herein report a rare case of BCR-ABL1-positive B-lymphoblastic lymphoma (B-LBL). An 18-year-old woman had a history of persistent left-sided chest pain. Positron emission tomography showed increased metabolic activity in the fifth rib, duodenum, and pancreas. The pathological findings of the pancreas, duodenum, and bone marrow confirmed the diagnosis of B-LBL. Polymerase chain reaction of duodenum and bone marrow also revealed a minor BCR-ABL1 fusion gene. She was diagnosed with BCR-ABL1-positive B-LBL and administered dasatinib and prednisolone. She achieved complete remission two weeks after the initiation of the treatment. She received stem cell transplantation after consolidation chemotherapy and sustained complete remission.

Maternal Knowledge Associated with the Prevalence of Iron and Folic Acid Supplementation Among Pregnant Women in Muntinlupa, Philippines: A Cross-Sectional Study.

PURPOSE: The World Health Organization advocates that all pregnant women in areas where anemia is prevalent receive supplements of iron and folic acid. However, owing to a myriad of factors, the uptake of iron and folic acid supplementation (IFAS) is still low in many countries. Therefore, this study was conducted to assess the prevalence of IFAS and its associated factors among pregnant women. PATIENTS AND METHODS: A cross-sectional study was conducted at a hospital in Muntinlupa, Philippines, between March and August 2019 among 280 pregnant women. A systematic random sampling technique was used to select participants. Data were collected using interviewer-administered questionnaires. Multivariable logistic regression analyses were employed to identify factors associated with the prevalence of IFAS among pregnant women. RESULTS: Among 280 pregnant women, a majority (85.6%, n= 238) took IFAS during pregnancy. Among the respondents, 128 (45.9%) women had knowledge about signs and symptoms of anemia, 126 (45.3%) had knowledge of the benefits associated with IFAS, and 42 (15.4%) had knowledge about side effects associated with IFAS. The main sources of information about IFAS were health care providers (41.8%), followed by community health workers (CHWs) (14.6%). Maternal knowledge concerning IFAS benefits (OR = 2.50, CI = 1.04-5.97, p=0.04) was positively associated with the prevalence of IFAS. CONCLUSION: Maternal knowledge about the benefits of taking IFAS was significantly associated with the prevalence of IFAS among pregnant women in Muntinlupa, Philippines. There is a pressing need to improve health education on the benefits of IFAS among pregnant women to increase its prevalence. This emphasizes the necessity of increased involvement of health care providers and CHWs to increase women's knowledge of IFAS benefits and support them through pregnancy.

Quality of life among people who use drugs living in poor urban communities in the Philippines.

BACKGROUND: The quality of life (QOL) and mental health of people who use drugs (PWUD) in the Philippines, especially those living in poor urban communities, are highly concerning due to the situations surrounding drug use and the ongoing hard-line antidrug policy. This study aimed to investigate the QOL and mental health status of PWUD, compare them with a comparison group with no history of drug use, and identify factors associated with QOL among Filipino PWUD. METHODS: A cross-sectional study was conducted with recruitment from a community-based rehabilitation programme and poor urban communities in Muntinlupa in 2018. QOL was measured using the WHOQOL-BREF, while psychological distress and posttraumatic stress disorder (PTSD) were measured using the Kessler Psychological Distress Scale (K-6) and the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5), respectively. Multivariable linear regressions with each WHOQOL-BREF domain as a dependent factor were conducted to establish three predictions: age- and gender-adjusted QOL means, factors associated with QOL among PWUD, and interaction of lifetime drug use with each covariate. RESULTS: In total, 272 PWUD and 402 comparison participants were recruited. Most PWUD were current drug users (53%), primarily of methamphetamine (70%). Among PWUD, the prevalence of moderate to severe psychological distress was 70%, and probable PTSD was 28%-both rates higher than those among the comparison group. All four QOL domain scores (physical, psychological, social, and environmental) of PWUD were lower than those of the comparison group. Multivariable regressions showed that psychological distress, current drug use, selling drugs, experiencing discrimination, and being never-married were associated with lower QOL. Higher individual income, household resources, social activity participation, and service use for drug use problems were associated with higher QOL among PWUD. Stratified and interaction analyses revealed that the QOL of PWUD was more sensitive to changes in individual income relative to the QOL of comparison group. CONCLUSION: A comprehensive intervention addressing psychological distress reduction, economic empowerment, and social inclusion-complementary to abstinence-oriented programmes-may improve the well-being of Filipino PWUD.

Risk of Intracranial Hemorrhage and Short-Term Outcome in Patients with Minor Head Injury.

OBJECTIVE: To examine the occurrence of traumatic intracranial hemorrhage (tICH) and outcome in patients with minor head injury and assess the probable risk factors. METHODS: Patients with minor head injury who visited our hospital from January 2015 to July 2017 were registered consecutively, and enrolled patients were aged ≥18 years, visited within 24 hours of the injury, and had a Glasgow Coma Scale score of 15 at outpatient clinic or before the injury. RESULTS: Of the 1122 enrolled patients, 55 (4.9%) had tICH. An antiplatelet agent was administered in 114 patients, an anticoagulant agent was administered in 49 patients, and none of them were administered in 948 patients. A multivariate analysis of tICH identified it as a risk factor, showing significant difference between antiplatelet medication (P = 0.0312), fall from stairs (P = 0.0057), traffic accident (P = 0.0117), neurologic symptoms (P = 0.0091), and modified Rankin Scale (mRS) score before trauma (P < 0.0001). We also analyzed association of enlargement of tICH with different parameters and only anticoagulant medication indicated an increased risk (P = 0.0005). Thirty patients (2.6%) were dependent or died at discharge (mRS 3-6). The mRS score before trauma (P < 0.0001), tICH (P < 0.0001), spinal injury (P < 0.0001), and enlargement of intracranial hemorrhage (P = 0.0008) indicated an increased probability of morbidity (mRS 3-6) in multivariate analysis. CONCLUSIONS: Antiplatelet and anticoagulant medications were risk factor for tICH and enlargement of tICH in patients with minor head injury, respectively. A pretrauma condition of disability/dependence is an important risk factor for tICH and outcome.

Pathological assessment of the lymph node biopsies for lymphadenopathy in rheumatoid arthritis.

Objectives: To assess the incidence of reactive lymph node hyperplasia (RLH) and the diagnostic characteristics that can help differentiate it from lymphoproliferative disorders (LPD) in patients with rheumatoid arthritis (RA).Methods: Data on patient characteristic from 32 consecutive RA patients with lymphadenopathy at a single medical center over a 6-year period were collected and analyzed to determine whether any of these characteristics can differentiated RLH from LPD.Results: LPD including methotrexate (MTX) - associated LPD (MTX-LPD) and RLH were diagnosed in 19 and 10 patients, respectively. Conclusive diagnosis was not reached in the remaining three cases and they were regarded as grey-zone cases. Age, levels of lactate dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R), as well as maximum standardized uptake value (SUVmax), were significantly higher in LPD than in RLH patients. The diagnosis cut-off values for these parameters were 66 year, 169 U/L, 899 U/mL and 8.18, respectively, based on the receiver operating characteristics curve analysis for both RLH and LPD.Conclusions: About one-third of patients with RA who presented with lymphadenopathy had reactive lymph node enlargement. Older age and higher levels of LDH, sIL-2R, and SUVmax are more associated with LPD than should be considered when deciding to perform a biopsy.

[A Case of Segmental Arterial Mediolysis:Subarachnoid Hemorrhage Followed by Abdominal Bleeding].

We describe a case involving subarachnoid and intraperitoneal hemorrhage due to segmental arterial mediolysis(SAM). A 77-year-old female patient with sudden subarachnoid hemorrhage was immediately transferred to our institution. The hemorrhage was classified as grade 2 according to the World Federation of Neurosurgical Societies system. The patient was a non-smoker and did not drink alcohol regularly. A right internal carotid aneurysm was detected using CT angiography and was clipped during frontotemporal craniotomy. Bleeding was observed from the anterior wall of the internal carotid artery, and the tear was clipped. The patient had an uneventful postoperative course until sudden cardiopulmonary arrest eight days after craniotomy. She died of massive intraperitoneal hemorrhage. Autopsy revealed that the hemorrhage was due to dissection of the celiac artery. Tunica media denaturation was observed not only in the celiac artery, but also in the splenic and internal carotid arteries, which exhibited ruptured aneurysms, and the patient was diagnosed with segmental arterial mediolysis(SAM). SAM is an arterial degenerative disease affecting the medial layer of the arterial and dissecting walls. Multiple lesions are sometimes found. Radiographic imaging findings of SAM are similar to those of dissecting aneurysms, which are characterized by a single continuous dissection of the medial layer. As observed in this case, abdominal bleeding caused by SAM can occur after intracranial bleeding. When surgeons encounter unusual intracranial dissecting aneurysms, SAM should be considered as a differential diagnosis.

Novel oxindole derivatives prevent oxidative stress-induced cell death in mouse hippocampal HT22 cells.

The current medical and surgical therapies for neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease offer symptomatic relief but do not provide a cure. Thus, small synthetic compounds that protect neuronal cells from degeneration are critically needed to prevent and treat these. Oxidative stress has been implicated in various pathophysiological conditions, including neurodegenerative diseases. In a search for neuroprotective agents against oxidative stress using the murine hippocampal HT22 cell line, we found a novel oxindole compound, GIF-0726-r, which prevented oxidative stress-induced cell death, including glutamate-induced oxytosis and erastin-induced ferroptosis. This compound also exerted a protective effect on tunicamycin-induced ER stress to a lesser extent but had no effect on campthothecin-, etoposide- or staurosporine-induced apoptosis. In addition, GIF-0726-r was also found to be effective after the occurrence of oxidative stress. GIF-0726-r was capable of inhibiting reactive oxygen species accumulation and Ca2+ influx, a presumed executor in cell death, and was capable of activating the antioxidant response element, which is a cis-acting regulatory element in promoter regions of several genes encoding phase II detoxification enzymes and antioxidant proteins. These results suggest that GIF-0726-r is a low-molecular-weight compound that prevents neuronal cell death through attenuation of oxidative stress. Among the more than 200 derivatives of the GIF-0726-r synthesized, we identified the 11 most potent activators of the antioxidant response element and characterized their neuroprotective activity in HT22 cells.

[Characteristics of male shift workers' drinking habits and factors related to drinking problems].

Objectives　To clarify the characteristics of shift workers' drinking habits, as well as factors related to their drinking problems, and obtain an insight into the early detection of such problems and appropriate interventions.Methods　An anonymous self-completed questionnaire survey was conducted involving all employees of a factory. All the shift workers were male. Considering the sex differences, we excluded daytime female workers from the study. The number of participants was 230. The questionnaire inquired the presence or absence of drinking problems, drinking habits, and factors related to these problems. We analyzed the relationship between shift work and drinking problems, shift work and each drinking habit, and drinking problems and each drinking habit. Binomial logistic regression analysis using the backward elimination method was conducted, with "the presence/absence of alcohol related problems" as the dependent variable, and variables showing the value of P<0.20 through univariate analysis as independent variables, with age, inputted simultaneously.Results　The drinking habits of shift workers compared to daytime workers were characterized by a significantly higher percentage of those drinking "at home" (P=0.037). In addition, compared with daytime workers, shift workers showed a significantly higher percentage of those reporting a "desire to sleep well" as the reason for drinking (P=0.006), and a significantly higher percentage of those having a nightcap (P<0.001). Significant correlations were seen between increased risk of drinking problems and "having a nightcap" (OR 6.38, 95%CI: 2.11-19.29, P=0.001) as well as "having a heavy physical job stress burden" (OR 2.24, 95%CI: 1.11-4.51, P=0.024). On the other hand, "receiving support from family and friends" had a significant correlation with a reduced risk of drinking problems (OR 0.75, 95%CI:0.58-0.97, P=0.030).Conclusions　Characteristics of male shift workers' drinking habits and factors related to drinking problems indicated that the drinking habits of shift workers compared to daytime workers were characterized by a significantly higher percentage of those drinking "at home" and "having a nightcap". "Having a nightcap" and "having a heavy physical burden" were correlated with an increased risk of drinking problems in male shift workers, whereas "support from family and friends" was correlated with a reduced risk of drinking problems. It is considered important to understand difficulties in falling asleep after working the night shift and to support coping behaviors other than drinking. Furthermore, elucidation of the importance of support from friends and family is necessary.

An autopsy case of macroglobulinemia complicated with syndrome of inappropriate secretion of ADH (SIADH) like hyponatremia, hypopituitarism and AL amyloidosis.

An 88-year-old male patient with macroglobulinemia was admitted to our hospital because of severe hyponatremia and unconsciousness. Laboratory findings showed decreased inhibition of antidiuretic hormone (ADH) and he was diagnosed with syndrome of inappropriate secretion of ADH (SIADH). Hyponatremia improved with only limitation of water intake and the patient was followed up on a continuing outpatient basis. However, soon after discharge from hospital, his legs started swelling with edema and hyponatremia worsened. He was re-admitted due to a fall at home. Hyponatremia was observed at re-admission. A CRH challenge test showed partial dysfunction of ACTH secretion. Corticosteroid therapy was performed, but the patient subsequently died from pneumonia. Pathological findings at autopsy revealed invasion of plasma cells and amyloid depositions in multiple organs, including the pituitary, adrenal cortex, heart, liver, kidney, lymph nodes and bone marrow. Consistent with these results, fibrosis was observed in the anterior lobe of the pituitary, suggesting that the autopsy findings were related to the clinical observations and diagnosis. This is the first reported case of macroglobulinemia complicated with multiple hormone dysfunction.

Interaction of PICK1 with C-terminus of growth hormone-releasing hormone receptor (GHRHR) modulates trafficking and signal transduction of human GHRHR.

Release of growth hormone (GH) from the somatotroph is regulated by binding GH-releasing hormone (GHRH) to its cognate receptor (GHRHR), one of the members of the G protein-coupled receptor (GPCR) superfamily. Proteins bound to the carboxy (C)-terminus of GPCR have been reported to regulate intracellular trafficking and function of the receptor; however, no functionally significant protein associated with GHRHR has been reported. We have identified a protein interacting with C-kinase 1 (PICK1) as a binding partner of GHRHR. In vitro binding assay revealed the PDZ-domain of PICK1 and the last four amino acid residues of GHRHR were prerequisite for the interaction. Further, in vivo association of these proteins was confirmed. Immunostaining data of a stable cell line expressing GHRHR with or without PICK1 suggested the C-terminus of GHRHR promoted cell surface expression of GHRHR and PICK1 affected the kinetics of the cell surface expression of GHRHR. Furthermore, cAMP production assay showed the C-terminus of GHRHR is involved in the regulation of receptor activation, and the interaction of GHRHR with PICK1 may influence intensities of the signal response after ligand stimulation. Thus, the interaction of the C-terminus of GHRHR with PICK1 has a profound role in regulating the trafficking and the signaling of GHRHR. [Supplementary Figure: available only at http://dx.doi.org/10.1254/jphs.12287FP].

Inhibition of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase by beta-D-4-O-sulfo-N-acetylgalactosaminides bearing various hydrophobic aglycons.

N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) transfers sulfate to position 6 of GalNAc(4SO4) residues of chondroitin sulfate to yield chondroitin sulfate E (CS-E). We have previously demonstrated that phenyl-beta-D-GalNAc(4SO4) could serve as an acceptor for GalNAc4S-6ST, thereby inhibiting GalNAc4S-6ST competitively. In this paper we compared the inhibitory effects of various glycosides in which various hydrophobic aglycons were attached to D-GalNAc(4SO4) via ss anomeric configuration. p-Nitrophenyl-beta-D-GalNAc(4SO4) and p-chlorophenyl-beta-D-GalNAc(4SO4) were stronger inhibitors than phenyl-beta-D-GalNAc(4SO4). Among inhibitors examined here, 3-estradiol-beta-D-GalNAc(4SO4) was the strongest inhibitor; the Ki of 3-estradiol-beta-D-GalNAc(4SO4) for the competitive inhibition was 0.008 mM, which was much lower than the Ki of phenyl-beta-D-GalNAc(4SO4), 0.98 mM. In contrast, 7-estradiol-beta-D-GalNAc(4SO4) showed only weak inhibition to GalNAc4S-6ST. 3-Estradiol-beta-D-GalNAc(4SO4) did not inhibit chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase under the concentration where GalNAc4S-6ST was inhibited by 90%. When 3-estradiol-beta-D-GalNAc(4SO4) was added to the culture medium of chondrosarcoma cells expressing human GalNAc4S-6ST, a significant, albeit small, reduction in the cellular synthesis of CS-E was observed. These results suggest that estradiol group of 3-estradiol-beta-D-GalNAc(4SO4) may enhance the inhibitory activity of the glycoside through increasing the affinity to the enzyme and may allow the glycosides to diffuse at a low efficiency into the cells to inhibit cellular synthesis of CS-E.