Humoral response against spike protein enhanced by fifth and sixth COVID-19 mRNA vaccine in the uninfected and infected subjects.

Antibody obtained by the coronavirus disease-19 (COVID-19) mRNA vaccine declines over time, and additional vaccinations are offered. It is not clear how repeated vaccination affects humoral immunity in uninfected individuals. We analyzed immunoglobulin G for spike protein (S-IgG) titers in COVID-19 uninfected and infected individuals vaccinated up to six times. The geometric mean S-IgG titers were 575.9 AU/mL and 369.0 AU/mL in those who received 6 and 5 doses less than 180 days after the last vaccination in uninfected subjects. In the 180-360 days after the last vaccination, the geometric mean S-IgG titers were 237.9 AU/mL and 128.6 AU/mL in the uninfected subjects who underwent five-dose and four-dose groups, respectively. Multivariate analysis showed that S-IgG titer increased 1.261-fold with each additional dose of mRNA vaccine. The S-IgG titers were 2.039-fold higher in the COVID-infected subjects compared to uninfected subjects. The positivity rate of nucleocapsid antibodies, suggesting a history of COVID-19, decreased 82% and 30% of COVID-infected cases after 180 and 360 days of infection, respectively. This result suggested that repeated vaccination with the COVID-19 mRNA vaccine may increase antibody titer in uninfected subjects.

[A case of pulmonary Mycobacterium kansasii infection with pleural effusion, distinguished from pulmonary tuberculosis].

A case of pulmonary Mycobacterium kansasii infection with pleural effusion is very rare. We report a case of pulmonary Mycobacterium kansasii infection with pleural effusion, distinguished from pulmonary tuberculosis. A 44-year-old man presented to a clinic with a productive cough, sputum, and loss of appetite for several months. Chest X-ray and chest computed tomography (CT) showed right pleural effusion, centrilobular nodules and infiltrative shadows with cavities in the bilateral lung fields. The direct smear examination showed positive acid-fast bacilli (Gaffky 5). He was referred to our hospital for suspected recurrent pulmonary tuberculosis. We started anti-tuberculosis drugs because pulmonary tuberculosis complicated with pleurisy was first suspected from the findings of high ADA level (78.6 IU/l) of the effusion and positive result of interferon-gamma release assay (QuantiFERON TB-2G). But Mycobacterium tuberculosis and M. avium complex was not identified by the polymerase chain reaction method and the culture of the sputum was negative. At a later date, Mycobacterium kansasii was detected by sputum culture. The patient was diagnosed as pulmonary Mycobacterium kansasii infection and treatment with anti-tuberculosis drugs including RFP resulted in a good clinical response. This case was a rare case of pulmonary Mycobacterium kansasii infection with pleural effusion, distinguished from pulmonary tuberculosis.

[A clinical investigation of seven patients with pulmonary tuberculosis who developed mixed liver injury during oral anti-tuberculosis treatment].

BACKGROUND: Liver injury is the most common and clinically significant adverse reaction to anti-tuberculosis drugs, sometimes resulting in a fatal outcome. It has been reported that liver injury induced by isoniazid and pyrazinamide, which has the potential to cause hepatocellular injury, has a risk of becoming severe; while an injury induced by rifampicin, which has the potential to cause cholestatic injury, rarely becomes severe. However, mixed liver injury has not been studied thoroughly. METHODS: Of 321 tuberculosis patients who were admitted and treated in our hospital over the past 5 years, 7 patients (2.1 %) who developed mixed liver injury due to the use of antituberculosis drugs were clinically investigated through their medical records. RESULTS: There were 4 male patients and 3 female patients, with a mean age of 66.7 (59-85) years. The mean duration from the start of oral anti-tuberculosis drugs to the onset of mixed liver injury was 28.5 days. In 2 of the patients, the event occurred within 2 weeks. Two of them had a total bilirubin level of > 5 mg/dl at the time of diagnosis. In 6 of the 7 patients, the liver injury improved on discontinuation of the anti-tuberculosis drugs. In the remaining 1 patient, the liver injury progressed even after discontinuation of the oral treatment, leading to death. CONCLUSION: Since mixed liver injury sometimes results in a fatal outcome, it is necessary to take adequate precautions.

Selective silencing of a mutant transthyretin allele by small interfering RNAs.

Familial amyloidotic polyneuropathy (FAP) is a hereditary systemic amyloidosis caused by dominantly acting missense mutations in the gene encoding transthyretin (TTR). The most common mutant TTR is of the Val30Met type, which results from a point mutation. Because the major constituent of amyloid fibrils is mutant TTR, agents that selectively suppress mutant TTR expression could be powerful therapeutic tools. This study has been performed to evaluate the use of small interfering RNAs (siRNAs) for the selective silencing of mutant Val30Met TTR in cell culture systems. We have identified an siRNA that specifically inhibits mutant, but not wild-type, TTR expression even in cells expressing both alleles. Thus, this siRNA-based approach may have potential for the gene therapy of FAP.