Search for protein kinase(s) related to cell growth or viability maintenance in the presence of ethanol in budding and fission yeasts.

Alcohol fermentation comprises two phases: phase 1, alcohol fermentation occurs while yeast cells proliferate; phase 2, growth stops and alcohol fermentation continues. We categorized genes related to proliferation in low ethanol (phase 1) and viability in high ethanol (phase 2) as Alcohol Growth Ability (AGA) and Alcohol Viability (ALV), respectively. Although genes required for phase 1 are examined in budding yeast, those for phase 2 are unknown. We set conditions for ALV screening, searched for protein kinases (PKs) related to ALV in budding yeast, and expanded two screenings to fission yeast. Bub1 kinase was important for proliferation in low ethanol but not for viability in high ethanol, suggesting that the important PKs differ between the two phases. It was indeed the case. Further, three common PKs were identified as AGA in both yeasts, suggesting that the important cellular mechanism in phase 1 is conserved in both yeasts, at least partially.

Analysis of the relationship between comorbid obstructive sleep apnea and clinical outcomes in patients with asthma in Japan.

BACKGROUND: Asthma and obstructive sleep apnea (OSA) are prevalent chronic respiratory disorders, which often coexist and interact with each other. Obesity is an important risk factor shared by them. The rate of obesity is lower in Japan versus Western countries. Hence, the co-existence of asthma and OSA has not been investigated in Japan. METHODS: Ninety-seven outpatients with asthma were recruited. Patients wore a portable monitor for sleep study. Background data, pulmonary function, blood tests, and patient-reported outcomes including gastroesophageal reflux disease, sleepiness, sleep quality, asthma control, cough and respiratory symptoms, and health status, were assessed. RESULTS: Of the patients, 19 (19.6 %), 40 (41.2 %), 24 (24.7 %), and 14 (14.4 %) were classified into non-, mild, moderate, and severe OSA groups. Non-OSA patients were younger than those in other groups (p < 0.05). The BMI of patients with moderate and severe OSA, was higher than that of non-OSA patients (p < 0.05). Pulmonary function, FeNO, serum IgE, and the number of peripheral eosinophils were not significantly different between groups. Nonetheless, compared with the other groups, treatment step was the highest, and the Asthma Control Test, Leicester Cough Questionnaire, COPD Assessment Test, and Asthma Health Questionnaire-33 yielded worst scores in the severe OSA group, and predicted the severe OSA after adjustment by BMI. CONCLUSIONS: Moderate and severe OSA are highly prevalent among patients with asthma in Japan. Pulmonary function did not differ between groups. However, patients with asthma and severe OSA were linked to more asthma treatment, worse asthma control, more symptoms and cough, and worse health status.

Obstructive pneumonia with bronchial foreign body: A case report.

The age of predilection for foreign body aspiration into the lower airway shows a bimodal distribution, with the majority of cases occurring in children or infants and in the elderly. Although several pediatric airway foreign bodies have been summarized, in adults, bronchial foreign bodies are relatively uncommon. There are a variety of symptoms induced by airway foreign bodies, although the typical symptoms of some bronchial foreign bodies are cough. Bronchial foreign bodies, especially in the elderly, may have few symptoms and it is necessary for careful identification. Therefore, it is very important to carefully perform medical consultations about current and past medical history. Herein, we report a case of an elderly Japanese with obstructive pneumonia with a bronchial foreign body of fish bone with a long history of cough. It is known that people in some countries such as Japan have a habit of eating fish. Therefore, it is necessary to more carefully explore the possibility of some bronchial foreign body such as a fish bone, when we observe symptoms of persistent cough in such countries.

DOPA pheomelanin is increased in nigral neuromelanin of Parkinson's disease.

Neuromelanin (NM) in dopaminergic neurons of human substantia nigra (SN) has a melanic component that consists of pheomelanin and eumelanin moieties and has been proposed as a key factor contributing to dopaminergic neuron vulnerability in Parkinson's disease (PD). While eumelanin is considered as an antioxidant, pheomelanin and related oxidative stress are associated with compromised drug and metal ion binding and melanoma risk. Using postmortem SN from patients with PD or Alzheimer's disease (AD) and unaffected controls, we identified increased L-3,4-dihydroxyphenylalanine (DOPA) pheomelanin and increased ratios of dopamine (DA) pheomelanin markers to DA in PD SN compared to controls. Eumelanins derived from both DOPA and DA were reduced in PD group. In addition, we report an increase in DOPA pheomelanin relative to DA pheomelanin in PD SN. In AD SN, we observed unaltered melanin markers despite reduced DOPA compared to controls. Furthermore, synthetic DOPA pheomelanin induced neuronal cell death in vitro while synthetic DOPA eumelanin showed no significant effect on cell viability. Our findings provide insights into the different roles of pheomelanin and eumelanin in PD pathophysiology. We anticipate our study will lead to further investigations on pheomelanin and eumelanin individually as biomarkers and possibly therapeutic targets for PD.

IgG4-related lung disease with multifocal pulmonary consolidations near the pleura: A case report.

RATIONALE: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a systemic immune-mediated condition that can cause fibroinflammatory lesions in multiple organs. Approximately 35% of IgG4-RD patients have some symptoms in the chest and IgG4-related lung disease (IgG4-RLD) is observed in about 10% of IgG4-RD cases. In addition, it is thought that glucocorticoid therapy is effective for IgG4-RD and IgG4-RLD. It is difficult to diagnose IgG4-RLD complicated with another lung disease. PATIENT CONCERNS: An 85-year-old Japanese man was hospitalized due to pulmonary consolidations just below the pleura in chest computed tomography while being treated with antibiotics. Previously, an upper lobectomy of the right lung was performed for an upper lung mucinous adenocarcinoma, and he was diagnosed with chronic obstructive pulmonary disease. Although he took antibiotics before admission, C-reactive protein levels were elevated. DIAGNOSIS: IgG4 levels were also elevated (IgG4; 733 mg/dL), and lung biopsy histology showed an abundance of IgG4-positive plasma cell infiltration; about 40% of the affected area was occupied by such infiltration. Based on such findings, we finally diagnosed him as IgG4-RLD. INTERVENTIONS: We administered 20 mg/d prednisolone. OUTCOMES: About 2 weeks after administration of prednisolone by intravenous injection, his multifocal pulmonary consolidations just below the pleura were markedly improved and his pulmonary symptoms disappeared. Four weeks after glucocorticoid therapy, IgG4 levels decreased from 831 mg/dL (peak) to 547 mg/dL. LESSONS: We should consider IgG4-RLD, a rare disease, when lesions are detected as pulmonary consolidations near the pleura and are unresponsive to antibiotic therapy. Glucocorticoid therapy, however, is very effective for such IgG4-RLD.

Adult acetonemic vomiting complicated with low body weight in a subject with Mycobacterium avium complex pulmonary disease: a case report.

Pulmonary diseases often cause significant health issues and nutritional disorders. Weight loss and malnutrition are related to the severity of obstructive disorders. Therefore, patients with such conditions often experience low nutritional energy. Acetonemic vomiting is caused by acetonemic syndrome. Previously, it was believe that acetonemic vomiting was observed only in childhood. However, it was recently suggested that acetonemic vomiting can also occur in adults. It is also considered that acetonemic vomiting can occur in subjects with low body weight because stored carbohydrate levels are reduced and fats are mainly used for energy. Consequently, large amounts of acetone are produced, ultimately resulting in nausea and vomiting. In this study, we report a case of adult acetonemic vomiting complicated by low body weight in a subject with Mycobacterium avium complex pulmonary disease.

CD44 is critical for the enhancing effect of hyaluronan in allergen-specific sublingual immunotherapy in a murine model of chronic asthma.

Allergen-specific sublingual immunotherapy (SLIT) is a potentially effective disease-modification treatment for patients with allergic asthma. Because CD44 signaling enhances regulatory T (Treg) cell-induction, administering CD44 ligands such as hyaluronan (HA) with allergen-specific SLIT may enhance the therapeutic effects. We evaluated the role of CD44 in Treg cell-induction in T helper type 2 (Th2)-mediated chronic airway inflammation using CD44-/- mice and the efficacy of HA on SLIT in a Dermatophagoides farinae (Df)-induced murine model of chronic asthma. Th2 responses and Treg cell induction were evaluated in CD44-/- mice. We devised a new SLIT model of Df-induced chronic asthma utilizing HA as an adjuvant. The effects of HA added to the new SLIT model were evaluated by the early asthmatic response (EAR) and airway hyperresponsiveness (AHR), eosinophilic airway inflammation, and serum Df-specific IgE levels. Th2-mediated chronic eosinophilic airway inflammation was worse in CD44-/- mice compared with Df-sensitized wild-type (WT) mice. HA enhanced the effect of Df-induced Treg cells in a CD44-dependent manner. Sublingual Df treatment in combination with HA, but not alone, normalized EAR and AHR, and significantly reduced the serum IgE levels and the bronchoalveolar lavage fluid (BALF) eosinophil number. HA also induced Treg cells in a Df-sensitized spleen cell culture in a CD44-dependent manner. The treatment-enhancing effects of HA in this SLIT model were diminished in CD44-/- mice. CD44 is a key contributor to Treg cell induction and critical for the enhancing effects of HA in a Df-induced murine model of chronic asthma.

Clinical Utility of Ultrasound-Guided Attenuation Parameter for the Detection and Quantification of Hepatic Steatosis in Patients with Fatty Liver Diagnosed by Computed Tomography.

This retrospective study was aimed (i) at elucidating the correlation between fatty liver diagnoses based on the plain computed tomography (CT) value and those based on the attenuation coefficient (AC) value determined with the ultrasound-guided attenuation parameter (UGAP) and (ii) at evaluating the diagnostic power of AC values. We included 125 patients who underwent blood tests, abdominal ultrasonography and abdominal CT at our department between April 2020 and March 2021. Hepatic fat infiltration was categorized as S0 (<5%), S1 (≥5 and 30<%), S2 (≥30 and <50%) or S3 (≥50%). The diagnostic ability of UGAP-determined AC was evaluated using receiver operating characteristic (ROC) curve analysis, and the correlation between AC value and fatty liver grade by CT value. The coefficient of correlation (r) between the AC value and plain CT value was -0.6188, indicating a moderate relationship. For diagnosing grade ≥S1 (n = 44), the area under the ROC curve (AUROC) was 0.8541, sensitivity 84.1%, specificity 81.5% and cutoff value 0.676 dB/cm/MHz. In diagnosing grade ≥S2 (n = 35), the AUROC was 0.8603, sensitivity 88.6%, specificity 81.1% and cutoff value 0.694 dB/cm/MHz. In diagnosing grade = S3 (n = 18), the AUROC was 0.9016, sensitivity 94.5%, specificity 81.9% and cutoff value, 0.704 dB/cm/MHz. The AC value is useful in diagnosing fatty liver.

Role of interleukin 5-induced eosinophils in interleukin 33-triggered airway inflammation in mice.

BACKGROUND: Interleukin (IL)-5 is essential for allergen induced eosinophilic airway inflammation, but not activation of T helper type 2 (Th2) cells in the lung. Although an excessive Th2 reaction is observed without IL-5 signaling, the mechanisms have remained unknown. OBJECTIVE: To evaluate the negative-feedback mechanism in eosinophilic airway inflammation, we examined IL-33 triggered eosinophilic airway inflammation in IL-5Rα-/- mice. METHODS: Mice were administered intranasal IL-33 for 3 days. Airway hyperresponsiveness (AHR) was evaluated and bronchoalveolar lavage (BAL) was performed 24 h after the last IL-33 treatment. The number of inflammatory cells and cytokine levels in the BAL fluid (BALF) were analyzed, and histologic examination was performed. RESULTS: Compared with IL-33 treated wild-type (WT) mice, intranasal administration of IL-33 in IL-5Rα-/- mice reduced eosinophilic airway inflammation, AHR, and basement membrane thickening, while we found excessive IL-33 induced IL-5 and IL-13 production in the airway without IL-5 signaling. The numbers of eosinophils with a ringshaped nucleus (resident) and segmented nucleus (inflammatory) were increased in WT mice, but not in IL-5Rα-/- mice following intranasal administration of IL-33, and the numbers of SiglecF-positive eosinophils with (resident) or without (inflammatory) expression of CD62L were also significantly increased by IL-33 treatment in WT mice, but not in IL5Rα-/- mice. The number of ILC2 cells in the BALF was significantly higher in IL-33 treated IL-5Rα-/- mice than in IL-33 treated WT mice. CONCLUSIONS: These findings suggest the possibility that IL-5 induced eosinophils contribute to the negative-feedback mechanisms in IL-33 induced ILC2 mediated airway inflammation.

Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity.

Neurogenerative diseases, such as Parkinson's disease, are associated, not only with the selective loss of dopamine (DA), but also with the accumulation of reactive catechol-aldehyde, 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is formed as the immediate oxidation product of cytoplasmic DA by monoamine oxidase. DOPAL is well known to exhibit toxic effects on neuronal cells. Both catecholic and aldehyde groups seem to be associated with the neurotoxicity of DOPAL. However, the exact cause of toxicity caused by this compound remains unknown. Since the reactivity of DOPAL could be attributed to its immediate oxidation product, DOPAL-quinone, we examined the potential reactions of this toxic metabolite. The oxidation of DOPAL by mushroom tyrosinase at pH 5.3 produced conventional DOPAL-quinone, but oxidation at pH 7.4 produced the tautomeric quinone-methide, which gave rise to 3,4-dihydroxyphenylglycolaldehyde and 3,4-dihydroxybenzaldehyde as products through a series of reactions. When the oxidation reaction was performed in the presence of ascorbic acid, two additional products were detected, which were tentatively identified as the cyclized products, 5,6-dihydroxybenzofuran and 3,5,6-trihydroxybenzofuran. Physiological concentrations of Cu(II) ions could also cause the oxidation of DOPAL to DOPAL-quinone. DOPAL-quinone exhibited reactivity towards the cysteine residues of serum albumin. DOPAL-oligomer, the oxidation product of DOPAL, exhibited pro-oxidant activity oxidizing GSH to GSSG and producing hydrogen peroxide. These results indicate that DOPAL-quinone generates several toxic compounds that could augment the neurotoxicity of DOPAL.

The Oxidation of Equol by Tyrosinase Produces a Unique Di-ortho-Quinone: Possible Implications for Melanocyte Toxicity.

Equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman, EQ), one of the major intestinally derived metabolites of daidzein, the principal isoflavane found in soybeans and most soy foods, has recently attracted increased interest as a health-beneficial compound for estrogen-dependent diseases. However, based on its structure with two p-substituted phenols, this study aimed to examine whether EQ is a substrate for tyrosinase and whether it produces o-quinone metabolites that are highly cytotoxic to melanocyte. First, the tyrosinase-catalyzed oxidation of EQ was performed, which yielded three EQ-quinones. They were identified after being reduced to their corresponding catechols with NaBH4 or L-ascorbic acid. The binding of the EQ-quinones to N-acetyl-L-cysteine (NAC), glutathione (GSH), and bovine serum albumin via their cysteine residues was then examined. NAC and GSH afforded two mono-adducts and one di-adduct, which were identified by NMR and MS analysis. It was also found that EQ was oxidized to EQ-di-quinone in cells expressing human tyrosinase. Finally, it was confirmed that the EQ-oligomer, the EQ oxidation product, exerted potent pro-oxidant activity by oxidizing GSH to the oxidized GSSG and concomitantly producing H2O2. These results suggest that EQ-quinones could be cytotoxic to melanocytes due to their binding to cellular proteins.

Case Report: Severe Edema and Marked Weight Gain Induced by Marginal Thiamine Deficiency in a Patient With Alcohol Dependency and Type 2 Diabetes Mellitus.

Background: Patients with alcohol use disorder (AUD) may develop peripheral edema due to alcohol-related liver, renal, or heart disease. Thiamine deficiency is reported to occur in AUD and type 2 diabetes mellitus (T2DM). Thiamine deficiency may also cause peripheral edema. Thiamine is essential for optimal glucose metabolism through its role as an essential co-factor for key enzymes in intermediary metabolism. Since glucose metabolism worsens under diabetic conditions, it seems that a relative shortage of thiamine may occur more easily in patients with diabetes mellitus. Case Presentation: A 59-year-old Japanese man was admitted to the hospital with severe peripheral edema. His background history included alcohol liver disease (ALD), chronic renal failure (CRF), and T2DM. His body mass index (BMI) at admission was 37.7 kg/m2 and this represented a 30 kg increase in body weight over 2 months. Laboratory investigations showed anemia, liver and renal injury, hyperglycemia, and marginal hypothyroidism. The plasma thiamine diphosphate concentration was 20 ng/mL (reference range: 24-66 ng/mL). Diet therapy of 1,600 kcal/day and intravenous fursultiamine hydrochloride therapy (50 mg/once a day, seven days) was commenced in combination with intravenous diuretics. After one week, the plasma thiamine concentration was 853 ng/mL, and the patient's body weight had reduced by 18 kg. Conclusions: Patients with T2DM and AUD may develop severe peripheral edema in the context of marginal thiamine deficiency. Fursultiamine hydrochloride (50 mg/once a day, seven days) restored normal plasma thiamine concentrations and may have contributed to the rapid resolution of severe peripheral edema in this case. Empirical treatment with thiamine should be considered in patients with severe peripheral edema in the context of AUD and T2DM.

An unusual but unmissable link between summer-type hypersensitivity pneumonitis and asthma in an old house.

While hypersensitivity pneumonitis (HP) and asthma are usually recognized as different disease entities based on their different allergic mechanisms, they may have some connections. A previously healthy 54-year-old Japanese man with no history of allergic diseases was hospitalized due to fever and breathlessness. He had lived in an old musty wooden house. He was diagnosed with acute summer-type HP induced by Trichosporon asahii based on bilateral ground-glass opacities on chest computed tomography (CT), a high titer of serum anti-T. asahii antibody, an increased number of lymphocytes and a decreased CD4/CD8 ratio in bronchoalveolar lavage fluid (BALF) and lung pathology suggestive of HP. However, untypical increased eosinophils in BALF (25.2%) and infiltrative eosinophils around bronchial walls were observed. After systemic corticosteroid treatment was started, he recovered, and was discharged with oral prednisone. However, two weeks after returning to his former house, he had fever and severe cough, and was re-hospitalized. While chest CT showed no abnormal shadows indicating a worsening of HP, pulmonary function test revealed a typical obstructive defect and eosinophilic inflammation in his sputum. He spontaneously recovered after re-hospitalization without increasing any treatments. During this second hospitalization, he was diagnosed with asthma, although it remains to be determined whether both HP and asthma were caused by T. asahii. Clinicians should not miss the possible overlapping presentations between HP and asthma, caused by environmental antigens.

Mechanical insufflation-exsufflation-related bilateral pneumothorax.

Mechanical insufflation-exsufflation (MI-E) devices are frequently used in patients with respiratory muscle weakness to increase their cough peak flow and assist them in improving cough effectiveness and clearing mucus from the airways. An 89-year-old male was admitted to our university hospital due to fever and loss of appetite. He was diagnosed with lung abscess and pulmonary nontuberculous mycobacterial disease. He was unable to independently expectorate phlegm due to frailty. Subsequently, MI-E was introduced. On day 3 after its introduction, chest X-ray examination revealed bilateral pneumothorax, and use of the MI-E device was discontinued. After conservatively observing the clinical course, pneumothorax was improved on day 12 after it occurred. Although scientific evidence regarding MI-E is currently limited, healthcare professionals often do not have an alternative in clinical practice. However, treating physicians should consider the risk of MI-E-related pneumothorax, despite its low occurrence rate.

Thoracoscopic Findings in IgG4-related Pleuritis.

A 46-year-old Japanese man was admitted to our hospital with a 1-year history of dyspnea and persistent right-dominant bilateral pleural effusions. Chest and abdominal computed tomography (CT) revealed no notable findings apart from the bilateral pleural effusions. 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) positron emission tomography-CT showed no accumulation of FDG in the thorax and abdomen. Thoracoscopy revealed numerous small (approximately 2-3 mm in size), blister-like nodules on the left parietal pleura extending from the lower third of the chest wall to the diaphragm. A pathological examination revealed lymphocyte and plasma cell infiltrates with increasing numbers of IgG4-positive plasma cells in the fibrotic pleura, indicating IgG4-related pleuritis.

Elevated levels of periostin and TGF-ß1 in the bronchoalveolar lavage fluid of patients with idiopathic eosinophilic pneumonia.

BACKGROUND: Periostin is induced in bronchial epithelial cells and fibroblasts by various stimuli including interleukin (IL)13 and transforming growth factor (TGF)-ß1, and is involved in allergic diseases such as asthma and atopic dermatitis, playing an important role in tissue remodeling and fibrosis. The role of periostin in the pathogenesis of eosinophilic lung diseases, however, is unclear. OBJECTIVE: To examine the contribution of periostin to eosinophilic inflammation of the lung in humans, we evaluated periostin, IL-13, and TGF-ß1 levels in the bronchoalveolar lavage fluid (BALF) of patients with eosinophilic pneumonia (EP). METHODS: Periostin, IL-13, and TGF-ß1 concentrations in the BALF were measured by enzyme-linked immunosorbent assay in patients with acute EP, chronic EP, idiopathic pulmonary fibrosis (IPF), and sarcoidosis. Further, we analyzed the relationship between periostin, IL-13, and TGFß-1, levels and the number of inflammatory cells in the BALF. RESULTS: The absolute number of eosinophils, and the periostin, IL-13, and TGF-ß1 levels in the BALF were significantly higher in patients with EP than in patients with IPF and sarcoidosis. Concentrations of periostin significantly correlated with the concentrations of TGF-ß1, but not those of IL-13, in the BALF of patients with EP. Periostin levels also significantly correlated with the absolute number of eosinophils in the BALF of patients with IPF, but not EP. CONCLUSIONS: Our findings suggest that TGF-ß1 might increase the production of periostin in the lungs of patients with EP. Periostin might contribute the pathogenesis of not only EP, but also IPF.

The Oxidative Pathway to Dopamine-Protein Conjugates and Their Pro-Oxidant Activities: Implications for the Neurodegeneration of Parkinson's Disease.

Neuromelanin (NM) is a dark brown pigment found in dopaminergic neurons of the substantia nigra (SN) and in norepinephrinergic neurons of the locus coeruleus (LC). Although NM is thought to be involved in the etiology of Parkinson's disease (PD) because its content decreases in neurodegenerative diseases such as PD, details are still unknown. In this study, we characterized the biosynthetic pathway of the oxidation of dopamine (DA) by tyrosinase in the presence of thiol peptides and proteins using spectroscopic and high-performance liquid chromatography (HPLC) methods and we assessed the binding of DA via cysteine residues in proteins by oxidation catalyzed by redox-active metal ions. To examine whether the protein-bound DA conjugates exhibit pro-oxidant activities, we measured the depletion of glutathione (GSH) with the concomitant production of hydrogen peroxide. The results suggest that the fate of protein-bound DA conjugates depends on the structural features of the proteins and that DA-protein conjugates produced in the brain possess pro-oxidant activities, which may cause neurodegeneration due to the generation of reactive oxygen species (ROS) and the depletion of antioxidants.

Chloroplast nucleoids as a transformable network revealed by live imaging with a microfluidic device.

Chloroplast DNA is organized into DNA-protein conglomerates called chloroplast nucleoids, which are replicated, transcribed, and inherited. We applied live-imaging technology with a microfluidic device to examine the nature of chloroplast nucleoids in Chlamydomonas reinhardtii. We observed the dynamic and reversible dispersion of globular chloroplast nucleoids into a network structure in dividing chloroplasts. In the monokaryotic chloroplast (moc) mutant, in which chloroplast nucleoids are unequally distributed following chloroplast division due to a defect in MOC1, the early stages of chloroplast nucleoid formation occurred mainly in the proximal area. This suggests the chloroplast nucleoid transformable network consists of a highly compact core with proximal areas associated with cpDNA replication and nucleoid formation.

The Pro-Oxidant Activity of Pheomelanin is Significantly Enhanced by UVA Irradiation: Benzothiazole Moieties Are More Reactive than Benzothiazine Moieties.

It is generally considered that eumelanin (EM) is photoprotective while pheomelanin (PM) is phototoxic. A recent study using a mouse model demonstrated that PM produces reactive oxygen species (ROS) that cause DNA damage and eventually lead to melanomagenesis. A biochemical study showed that PM possesses a pro-oxidant activity. PM consists of benzothiazine (BT) and benzothiazole (BZ) moieties, BT moieties being transformed to BZ moieties by heat or light. In this study, we compared the effects of ultraviolet A (UVA) irradiation using synthetic PMs with different BT to BZ ratios and using various coat color mouse hairs. We found that UVA irradiation of BZ-PM increased glutathione (GSH) depletion and generated more H2O2 than UVA irradiation of BT-PM. Non-irradiated controls did not exhibit strong pro-oxidant activities. Upon UVA irradiation, yellow mouse hairs oxidized GSH and produced H2O2 faster than black or albino mouse hairs. Next, to examine the mechanism of the pro-oxidant activity of BT-PM and BZ-PM, we examined the pro-oxidant activities of 7-(2-amino-2-carboxyethyl)-dihydro-1,4-benzothiazine-3-carboxylic acid (DHBTCA) and 6-(2-amino-2-carboxyethyl)-4-hydroxybenzothiazole (BZ-AA) as BT and BZ monomers, respectively. Their pro-oxidant activities were similar, but a large difference was seen in the effects of ROS scavengers, which suggests that the redox reactions may proceed via singlet oxygen in BZ-AA and via superoxide anions in DHBTCA. These results show that UVA enhances the pro-oxidant activity of PM, in particular BZ-PM.