Immunogenicity and antigenicity of Plasmodium vivax merozoite surface protein 10

Among the proteins involved in the invasion by merozoite, the glycosylphosphatidylinositol-anchored proteins (GPI-APs) are suggested as potential vaccine candidates because of their localization to apical organelles and the surface; these candidates are predicted to play essential roles during invasion. As a GPI-AP, Plasmodium vivax merozoite surface protein 10 (PvMSP-10) induces high antibody titers. However, such high antibody titers have shown no protective efficacy for animals challenged with P. vivax parasites in a previous study. To adequately evaluate the immunogenicity and further characterize PvMSP-10 in order to understand its vaccine potential, we assessed its immunogenicity by immunizing BALB/c mice with cell-free expressed recombinant PvMSP-10 protein. The antigenicity of MSP-10 was analyzed, and we found 42 % sensitivity and 95 % specificity using serum samples from P. vivax-infected Korean patients. The IgG1 and IgG3 were the predominant immunoreactive antibodies against PvMSP-10 in vivax patient sera, and IgG1 and IgG3 and Th1-type cytokines were predominantly secreted in PvMSP-10-immunized mice. We conclude that the immunogenicity and antigenicity of MSP-10 may serve as a potential vaccine against vivax malaria.     

Drinking frequency modifies an association between salt intake and blood pressure: A cohort study

Salt sensitivity is one of the crucial risk factors of hypertension. The aim of the present prospective cohort study was to assess the clinical impact of alcohol drinking on an association between salt intake and blood pressure. The present study included 451 employees at a pharmaceutical company in Japan who underwent annual health checkups in both 2017 and 2018. The main exposure of interest was self‐reported drinking frequency at their first checkups: rarely, occasionally, and daily. To assess the association between the change of salt intake estimated from single‐spot urine specimens and that of blood pressure, the differences in systolic/diastolic blood pressure and salt intake between 2017 and 2018 were calculated for each subject. Multivariable‐adjusted linear regression models adjusting for clinically relevant factors clarified a drinking frequency‐dependent association between Δsalt intake and Δsystolic blood pressure (per 1 g/d of Δsalt intake adjusted β [95% confidence interval] 0.19 [−0.73, 1.12], 0.84 [0.14, 1.53], and 1.78 [0.86, 2.69] in rare, occasional, and daily drinkers). A similar association between Δsalt intake and Δdiastolic blood pressure was also observed (−0.24 [−1.02, 0.54], 0.67 (0.18, 1.16), 0.95 [0.38, 1.51], in rare, occasional, and daily drinkers). The interactions between drinking frequency and Δsalt intake were found to be statistically significant (P for interaction = .028 and .006 for ∆systolic blood pressure and ∆diastolic blood pressure, respectively). The present study identified enhanced salt sensitivity in the subjects who drink at a higher frequency, suggesting that the reduction in alcohol consumption may improve salt sensitivity in higher frequency drinkers.     

A patient with esophageal cancer with bone metastasis who achieved pain relief with repetitive administration of strontium-89 chloride

A 75-year-old woman was diagnosed with esophageal cancer with difficulty in swallowing. She had a past history of rheumatoid arthritis, scleroderma, interstitial pneumonia, angina pectoris (with coronary artery bypass surgery) and arrhythmia (with pacemaker implantation). She refused surgery, and chemotherapy and radiotherapy were not performed because of the high risk accompanied with multiple comorbidities. She received proton therapy at another hospital and the primary lesion shrank. Bone metastasis in the thoracic vertebrae was diagnosed 10 months after diagnosis of esophageal cancer. Non-steroidal anti-inflammatory drugs and zoledronic acid were administered for back pain. Oxycodone was also administered but discontinued due to nausea. After strontium-89 (⁸⁹Sr) chloride administration, her back pain was relieved. ⁸⁹Sr was administered five times every 3 months, and the pain did not worsen until her death due to pneumonia 2 years after diagnosis of esophageal cancer. ⁸⁹Sr was effective for pain from bone metastasis of esophageal cancer, and its repeated administration was safe.     

Association between changes in cortical and jaw motor activities during sleep

In normal sleep, cortical EEG activity is influenced by the balance in the activities of subcortical neurons in relation to the cyclic changes of sleep states. As well, jaw motor excitability is altered under the activity of sleep regulatory mechanism. Transient arousals (e.g., micro-arousal) are associated with a brief change of cortical activity and an increase of jaw motor activity. During this period, various types of jaw motor activities are occasionally found to occur, with either non-specific or specific patterns such as rhythmic activations. Exaggeration of the jaw motor activities during sleep can be seen in patients with sleep bruxism. Although cortical activity reflects arousal level and is correlated with the activity level of jaw muscles during sleep, it remains to be investigated whether or not cortex plays one of the sources of descending excitatory drive shaping a variety of jaw motor activities.     

CD48 as a novel molecular target for antibody therapy in multiple myeloma

Monoclonal antibody (mAb) drugs are desirable for the improvement of multiple myeloma (MM) treatment. In this study, we found for the first time that CD48 was highly expressed on MM plasma cells. In 22 out of 24 MM patients, CD48 was expressed on more than 90% of MM plasma cells at significantly higher levels than it was on normal lymphocytes and monocytes. CD48 was only weakly expressed on some CD34(+) haematopoietic stem/progenitor cells, and not expressed on erythrocytes or platelets. We next examined whether CD48 could serve as a target antigen for mAb therapy against MM. A newly generated in-house anti-CD48 mAb induced mild antibody-dependent cell-mediated cytotoxicity and marked complement-dependent cytotoxicity against not only MM cell lines but also primary MM plasma cells in vitro. Administration of the anti-CD48 mAb significantly inhibited tumour growth in severe combined immunodeficient mice inoculated subcutaneously with MM cells. Furthermore, anti-CD48 mAb treatment inhibited growth of MM cells transplanted directly into murine bone marrow. Finally and importantly, we demonstrated that the anti-CD48 mAb did not damage normal CD34(+) haematopoietic stem/progenitor cells. These results suggest that the anti-CD48 mAb has the potential to become an effective therapeutic mAb against MM.