We investigated the "laser adjuvant" that improved vaccine efficacy, via combining non-invasive near-infrared red (NIR) light irradiation and intradermal influenza vaccine and discovered the crucial role of reactive oxygen species (ROS) and mast cells. This study elucidates the effects of a new wavelength (1270 nm) of NIR light that exhibits a similar adjuvant effect at lower energy on mast cells and mouse skin, revealing ROS and ATP production via mitochondrial photoreception, increased chemokine mRNA expression, and durable antibody titers in immunized mice. These findings highlight the clinical potential of 1270 nm NIR light, demonstrating the wavelength-specific effect of laser adjuvants.
Journal Article Characterization of the Measles Virus Isolated from the Brain of a Patient with Immunosuppressive Measles Encephalitis Get access Masanobu Ohuchi, Masanobu Ohuchi Departments of Microbiology and Pediatrics, Medical College of Oita, Oita, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Reiko Ohuchi, Reiko Ohuchi Departments of Microbiology and Pediatrics, Medical College of Oita, Oita, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Kumato Mifune, Kumato Mifune Departments of Microbiology and Pediatrics, Medical College of Oita, Oita, Japan Please address requests for reprints to Dr. Kumato Mifune, Department of Microbiology, Medical College of Oita, Hazamacho, Oita 879-56, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Takanobu Ishihara, Takanobu Ishihara Departments of Microbiology and Pediatrics, Medical College of Oita, Oita, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Teruyuki Ogawa Teruyuki Ogawa Departments of Microbiology and Pediatrics, Medical College of Oita, Oita, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 156, Issue 3, September 1987, Pages 436–441, https://doi.org/10.1093/infdis/156.3.436 Published: 01 September 1987 Article history Received: 12 November 1986 Revision received: 09 April 1987 Published: 01 September 1987
Abstract Background Amikacin liposome inhalation suspension (ALIS), which efficiently allows amikacin to reach the pulmonary periphery for drug effect while minimising systemic adverse effects, was recently approved for the treatment of Mycobacterium avium complex (MAC) infections. The international phase 3 open-label clinical trials showed promising results, contributing to sputum culture conversion, but few reports have examined the efficacy and adverse effects using real-world data. We have identified the clinical outcome and adverse effects in the early-phase of treatment to use ALIS more effectively and safely in clinical practice. Methods The study population consisted of patients with MAC lung disease (MAC-LD) who were introduced to ALIS therapy after July 2021 at Keio University Hospital due to poor response to multidrug therapy. The sputum smear/culture results, symptoms and adverse effects of the early-phase of ALIS inhalation therapy were retrospectively reviewed. The serum amikacin concentrations in the earliest phase were also measured to assess PK/PD. Results A total of 11 cases (9 women; median age 64.6 years) were included in this study. The median disease duration of MAC-LD was 13.7 years, and all patients had a positive culture at the beginning of ALIS inhalation. Eight patients (72.7%) completed ALIS inhalation without interruption during the first month of treatment. Five patients (45.5%) were smear-negative at the start and none were positive at the 1 month follow-up. Three of the six patients (50.0%) who were sputum-smear-positive at the initiation were confirmed to have become sputum-smear-negative within one month, including one culture conversion. ALIS inhalation therapy caused some adverse effects in nine patients (81.8%); however, no serious systemic adverse effects were observed. The most common adverse effect was hoarseness (72.7%), which mostly occurred around 1 week after initiation. The medians of peak serum amikacin concentrations were 1.4 and 2.3 µg/mL for the first and third inhalations, respectively. On the other hand, trough serum concentrations just before the third inhalation were < 1.2 µg/mL in all patients. Conclusions ALIS therapy might be a treatment option for patients having refractory MAC infection with long disease duration who have had a poor response to guideline-based therapy.
Relapsing polychondritis (RP) is a rare inflammatory disorder involving immune-mediated destruction of cartilaginous structures. Herein, we present the first report of a strong association between COVID-19 vaccination and RP development. Clinicians should be aware that RP is among the autoimmune diseases that can develop after mRNA vaccination.
With the development of laser technology in the 1960s, a technique was developed to inject intradermal vaccines immediately after irradiating the skin with laser light to elicit an adjuvant effect, referred to as “laser adjuvant.” We have been investigating the mechanism of laser adjuvant in influenza mouse models using noninvasive continuous-wave (CW) near-infrared (NIR) light mainly at a wavelength of 1064 nm, and have shown that the production of reactive-oxygen-species (ROS) in the skin and mast cells in the skin tissue plays an important role in the laser adjuvant effect. The new wavelength of 1270 nm NIR light is characterized by its ability to elicit the same vaccine adjuvant effect as other wavelengths at a lower energy, and may be suitable for clinical applications. In this study, we investigated the physiological activity of CW1270 nm NIR light in mast cells, its biological activity on mouse skin, and the durability of the vaccine adjuvant effect in influenza vaccine mouse models. We show that irradiation of mast cells with 1270 nm NIR light produced ROS and ATP, and irradiation of isolated mitochondria also produced ATP. In mouse skin, the relative expression levels of chemokine mRNAs, such as Ccl2 and Ccl20 , were increased by irradiation with 1270 and 1064 nm NIR light at minimum safe irradiance. However, the relative expression of Nfkb1 was increased at 1064 nm, but not at 1270 nm. Serum anti-influenza IgG antibody titers increased early after immunization with 1064 nm, whereas with 1270 nm, there was not only an early response of antibody production but also persistence of antibody titers over the medium- to long-term. Thus, to our knowledge, we show for the first time that 1270 nm NIR light induces ROS and ATP production in mitochondria as photoreceptors, initiating a cascade of laser adjuvant effects for intradermal vaccines. Additionally, we demonstrate that there are wavelength-specific variations in the mechanisms and effects of laser adjuvants. In conclusion, CW1270 nm NIR light is expected to be clinically applicable as a novel laser adjuvant that is equivalent or superior to 1064 nm NIR light, because it can be operated at low energy and has a wavelength-specific adjuvant effect with medium- to long-lasting antibody titer.
Since nontuberculous mycobacterial pulmonary disease (NTM-PD) is common in middle-aged/elderly slender women at risk of osteoporosis, we hypothesized that NTM-PD could be associated with osteoporosis. The study aimed to evaluate the prevalence of osteoporosis in patients with NTM-PD compared with that in the general population and determine the factors associated with osteoporosis in the subjects, including the serum estradiol (E2) and 25-hydroxyvitamin D (25OHD) levels.We have recruited 228 consecutive adult patients with NTM-PD from a prospective cohort study at the Keio University Hospital, who had no history of osteoporosis or osteoporosis-associated bone fracture but underwent dual-energy X-ray absorptiometry-based bone mineral density (BMD) evaluation from August 2017-September 2019. The E2 and 25OHD levels were measured in 165 patients with available stored serum samples. We performed multivariable logistic regression analyses for osteopenia and osteoporosis.Osteoporosis (T-score ≤ - 2.5) and osteopenia (T-score - 1 to - 2.5) were diagnosed in 35.1% and 36.8% of patients with NTM-PD, respectively. Compared with the general population, the proportion of osteoporosis was significantly higher in 50-59-, 60-69-, and 70-79-year-old women with NTM-PD. Multivariable analysis revealed that older age (adjusted odds ratio [aOR] for 1-year increase = 1.12; 95% confidence interval [CI] = 1.07-1.18), female sex (aOR = 36.3; 95% CI = 7.57-174), lower BMI (aOR for 1 kg/m2 decrease = 1.37; 95% CI = 1.14-1.65), and chronic Pseudomonas aeruginosa (PA) infection (aOR = 6.70; 95% CI = 1.07-41.8) were independently associated with osteoporosis. Additionally, multivariable analysis in 165 patients whose serum E2 and 25OHD levels were measured showed that both low E2 levels (< 10 pg/mL) and lower 25OHD levels were independently associated with osteoporosis.Middle-aged/elderly women with NTM-PD have a higher prevalence of osteoporosis than the general population. BMD screening should be considered in NTM-PD, especially in older females with severe diseases such as chronic PA infection and lower BMI, and low serum E2 and 25OHD levels.
Diffuse lung cysts occur owing to several diseases; however, diffuse cystic lung metastases are very rare in the case of lung cancer. We report a rare case of diffuse cystic lung metastases from lung adenocarcinoma and reviewed previously reported cases of cystic lung metastases for lung cancer and determined their characteristics.A 78-year-old Japanese woman with advanced lung adenocarcinoma was positive for the epidermal growth factor receptor gene mutation exon 21 L858R and had been treated with osimertinib. She presented with multiple bilaterally positioned thin-walled lung cysts and pneumothorax. Lung cysts were diagnosed as cystic lung metastases from lung cancer, and carboplatin, pemetrexed, and pembrolizumab were subsequently administered. All cysts markedly decreased in size, and some disappeared.Effective treatment methods for cystic lung metastases from lung cancer have not been reported. To our knowledge, this is the first case of cystic lung metastases that were successfully treated with chemotherapy.
