Effects of Ingesting Food Containing Heat-Killed Lactococcus lactis Strain Plasma on Fatigue and Immune-Related Indices after High Training Load: A Randomized, Double-Blind, Placebo-Controlled, and Parallel-Group Study.

Lactococcus lactis strain Plasma (LC-Plasma) is a unique lactic acid bacterium that activates plasmacytoid dendritic cells (pDCs). We evaluated the effect of LC-Plasma on fatigue indices and dendritic cells activity in athletes after 14 days' continuous exercise load. Thirty-seven participants were divided into two groups and consumed placebo (PL) or LC-Plasma capsules (containing 100 billion cells) daily for 14 days. Maturation markers on dendritic cells, blood parameters, physiological indices, and fatigue-related indices were recorded on days 1 and 15 (before and after exercise). Cumulative days of symptoms relating to physical conditions were also recorded during the continuous exercise period. We observed that CD86 as a maturation marker on pDCs was significantly higher and that cumulative days of fatigue were significantly fewer in the LC-Plasma group than in the Placebo group on day 15. We also conducted 2 h ergometer exercise on day 15 to evaluate fatigue. The results showed that autonomic fatigue parameters (LF/HF) were significantly lower in the LC-Plasma group. These results suggest that LC-Plasma supplementation alleviates fatigue accumulation and increases pDC activity caused by a continuous high training load.

Topical Sirolimus 0.2% Gel for the Management of Tuberous Sclerosis Complex-Related Cutaneous Manifestations: An Interim Analysis of Postmarketing Surveillance in Japan.

INTRODUCTION: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder affecting several organs, including skin. We sought to assess the real-world effectiveness and safety of a topical sirolimus 0.2% gel treatment for TSC-related cutaneous manifestations. METHODS: We conducted an interim analysis of postmarketing surveillance conducted in Japan over 52 weeks. A total of 635 and 630 patients were included in the safety and efficacy analysis sets, respectively. Improvement rate of overall cutaneous manifestations, responder rate of improvement in individual lesions, adverse events (AEs), adverse drug reactions (ADRs), and patient satisfaction level of topical sirolimus 0.2% gel treatment were evaluated along with patient characteristics associated with the improvement rate of cutaneous manifestations or safety. RESULTS: The mean age of the patients was 22.9 years and 46.1% were men. At week 52 of treatment, the overall improvement rate was 74.8% and the responder rate was the highest for facial angiofibroma (86.2%). Overall, the incidence rates of AEs and ADRs were 24.6% and 18.4%, respectively. Efficacy was associated with age (< 15, ≥ 15 to < 65, and ≥ 65 years, p = 0.010), duration of use (p < 0.001), and total dosage (p = 0.005). Safety was associated with age (< 15, ≥ 15 to < 65, and ≥ 65 years, p = 0.011) and duration of use (p < 0.001). However, when the broad age group (≥ 15 to < 65) was subcategorized by 10-year intervals, the incidence of ADRs was similar among the age groups with no significant differences. Hepatic or renal impairment or concomitant use of systemic mTOR inhibitors had no effect on the effectiveness or safety. Overall, 53% of patients were "very satisfied" or "satisfied" with the treatment received. CONCLUSIONS: Topical sirolimus 0.2% gel is effective in the management of TSC-related cutaneous manifestations and generally well tolerated. Age and duration of usage had a significant association with the effectiveness or safety of topical sirolimus 0.2% gel, whereas total dosage had a significant association with the effectiveness.

Lactococcus lactis Strain Plasma Intake Suppresses the Incidence of Dengue Fever-like Symptoms in Healthy Malaysians: A Randomized, Double-Blind, Placebo-Controlled Trial.

Dengue fever (DF) is a mosquito-borne disease still with no effective treatment or vaccine available. A randomized, placebo-controlled, double-blinded, parallel-group trial was undertaken to evaluate the efficacy of oral intake of Lactococcus lactis strain plasma (LC-Plasma) on the presentation and severity of DF-like symptoms among healthy volunteers. Study participants (320) were assigned into two groups, and consumed either placebo or LC-Plasma tablets (approximately 100 billion cells/day) for 8 weeks. The clinical symptoms of DF were self-recorded through questionnaires, and exposure to DENV was determined by serum antibody and/or DENV antigen tests. No significant differences between groups were observed for exposure to DENV, or the symptomatic ratio. Results obtained showed that participants from the LC-Plasma group reported a significant reduction in the cumulative incidence days of DF-like symptoms, which include fever (p < 0.001), muscle pain (p < 0.005), joint pain (p < 0.001), and pain behind the eyes (p < 0.001), compared to that of the placebo group. Subgroup analysis revealed a significantly (p < 0.05) reduced severity score in the LC-Plasma group when study sites were separately analyzed. Overall, our findings suggest that LC-Plasma supplementation reduces the cumulative days with DF-like symptoms, and the severity of the symptoms. Daily oral intake of LC-Plasma, hence, is shown to mitigate the DF-like symptoms.

The Effects of Dietary Supplementation of Lactococcus lactis Strain Plasma on Skin Microbiome and Skin Conditions in Healthy Subjects-A Randomized, Double-Blind, Placebo-Controlled Trial.

(1) Background: Lactococcus lactis strain Plasma (LC-Plasma) is a unique strain which directly activates plasmacytoid dendritic cells, resulting in the prevention against broad spectrum of viral infection. Additionally, we found that LC-Plasma intake stimulated skin immunity and prevents Staphylococcus aureus epicutaneous infection. The aim of this study was to investigate the effect of LC-Plasma dietary supplementation on skin microbiome, gene expression in the skin, and skin conditions in healthy subjects. (2) Method: A randomized, double-blind, placebo-controlled, parallel-group trial was conducted. Seventy healthy volunteers were enrolled and assigned into two groups receiving either placebo or LC-Plasma capsules (approximately 1 × 1011 cells/day) for 8 weeks. The skin microbiome was analyzed by NGS and qPCR. Gene expression was analyzed by qPCR and skin conditions were diagnosed by dermatologists before and after intervention. (3) Result: LC-Plasma supplementation prevented the decrease of Staphylococcus epidermidis and Staphylococcus pasteuri and overgrowth of Propionibacterium acnes. In addition, LC-Plasma supplementation suggested to increase the expression of antimicrobial peptide genes but not tight junction genes. Furthermore, the clinical scores of skin conditions were ameliorated by LC-Plasma supplementation. (4) Conclusions: Our findings provided the insights that the dietary supplementation of LC-Plasma might have stabilizing effects on seasonal change of skin microbiome and skin conditions in healthy subjects.

Lactococcus lactis Strain Plasma Improves Subjective Physical State and Presenteeism: A Randomized, Open-Label Crossover Study among Healthy Office Workers.

Maintaining employees' presenteeism is a major issue in the workplace. Simple and convenient methods to improve presenteeism are required. We investigated whether administering the lactic acid bacteria Lactococcus lactis strain Plasma (LC-Plasma) can improve the performance and physical condition of office workers. Subjects were randomly assigned to one of two groups: 1) an intake period (consumption of LC-Plasma-containing yogurt beverage) followed by a non-intake period, or 2) a non-intake period followed by an intake period. Each period lasted 4 weeks and there was a 4- week washout period between each. Assessment was conducted using the World Health Organization Health and Work Performance Questionnaire (HPQ), the Profile of Mood States (POMS) questionnaire and physical condition questionnaires. A total of 153 subjects were analyzed. Absolute presenteeism (as assessed by the HPQ) and vigor (as assessed by POMS) were significantly higher in the intake period than the non-intake period. The subject's physical health (as assessed by typical common cold symptoms, physical condition, sneezing or runny noses, coughing or sore throats, and lassitude) was also superior during the LC-Plasma intake period. Our results suggest that intake of LC-Plasma for 4 weeks improves work performance through reducing the risk of infection.

Safety and effectiveness of high-dose methotrexate (over 8 mg/week) in 2838 Japanese patients with rheumatoid arthritis: a postmarketing surveillance report.

Objectives: To confirm the safety and effectiveness of high-dose (>8 mg/week) methotrexate (MTX) for the treatment of rheumatoid arthritis in Japan.Methods: A postmarketing surveillance program enrolled Japanese patients with rheumatoid arthritis starting on high-dose MTX followed up for 24 or 52 weeks. Analyses for safety, risk factors affecting safety, and effectiveness were conducted.Results: The safety/effectiveness analysis sets included 2838/2779 and 335/326 patients in the 24 and 52-week follow-up groups, respectively. Incidence of adverse drug reactions (ADRs) and serious ADRs was 21.42 and 1.66% in the 24-week and 35.52 and 2.69% in the 52-week groups, respectively. The Disease Activity Score in 28 Joints (DAS28) was significantly decreased as early as four weeks from the start of high-dose MTX; after 24-week (4.09-3.21) and 52-week treatment (3.91-2.80; both p < .001). In a majority of patients at baseline who had high-to-moderate disease activity, the remission rate (defined as DAS28-4ESR <2.6) increased three-fold from 10.6% (baseline) to 33.0% (24-week) compared to patients with low disease activity whose remission rate increased two-fold from 24.0% (baseline) to 53.6% (24 weeks).Conclusion: High-dose MTX was well tolerated in Japanese patients, resulted in improved disease control, and can be considered a step forward in achieving treat-to-target goals.

The Effects of Plasmacytoid Dendritic Cell-Stimulative Lactic Acid Bacteria, Lactococcus lactis Strain Plasma, on Exercise-Induced Fatigue and Recovery via Immunomodulatory Action.

The unique lactic acid bacteria, Lactococcus lactis strain plasma (LC-Plasma), stimulates plasmacytoid dendritic cells, which play an important role in viral infection. The authors previously reported that LC-Plasma reduced the number of days athletes experienced cold-like symptoms and fatigue feelings after high-intensity exercise training; however, the mechanism was unclear. In this study, the authors investigated the effect of LC-Plasma on recovery from physical damage after single exercise on a treadmill in BALB/c mice model. Oral administration of LC-Plasma (AIN-93G + 0.029% LC-Plasma) for 4 weeks significantly improved the locomotor reduction after treadmill exercise. This effect was not detected in mice receiving Lactobacillus rhamnosus GG, representative probiotics strain. LC-Plasma also improved voluntary locomotor activity after exercise. Blood and muscle sample analysis indicated that LC-Plasma affects plasmacytoid dendritic cell activation, which, in turn, attenuates muscle degenerative genes and the concentration of fatigue-controlled cytokine transforming growth factor-ß.

Efficacy of heat-killed Lactococcus lactis JCM 5805 on immunity and fatigue during consecutive high intensity exercise in male athletes: a randomized, placebo-controlled, double-blinded trial.

BACKGROUND: Lactococcus lactis JCM 5805 (LC-Plasma) is a unique lactic acid bacteria (LAB) which activates plasmacytoid dendritic cells (pDC). We aimed to evaluate the effect of LC-Plasma on dendritic cell (DC) activity and subjective indices of upper respiratory tract infections (URTI) and fatigue in athletes under high intensity exercise. METHODS: We conducted a randomized, placebo-controlled, double-blinded trial. Fifty-one male subjects belonging to a university sports club were randomized into placebo (n = 25) and LC-Plasma (n = 26) groups. Individuals ingested placebo capsules containing cornstarch or LC-Plasma capsules containing 100 billion cells of heat-killed LC-Plasma per day for 13 days. During the intervention period, subjects performed high intensity exercise according to their sports club training regime. Blood and saliva sampling were obtained at days 1 and 14, and physical conditions were recorded in a diary. We investigated expression of maturation markers on DCs, muscle damage and stress markers and used student's t test adjusted by Bonferoni's method for multiple comparison between groups. These data were presented as mean ± SD. We also investigated cumulative days of symptoms regarding infections and fatigue and used Chi-square test for comparison between groups. These data were presented as cumulative number. RESULTS: CD86 as maturation marker on pDC was significantly increased in the LC-Plasma group at day 14 (Placebo: 296 ± 70 vs. LC-Plasma: 365 ± 115; Mean Fluorescent Intensity; p = 0.013). Cumulative days of URTI were significantly lower in the LC-Plasma group (Placebo: URTI positive 56, URTI negative 256 vs. LC-Plasma: URTI positive 39, URTI negative 299; days; p = 0.028) and symptoms like sneeze or running nose were significantly lower in the LC-Plasma group (Placebo: Symptom positive 52, Symptom negative 258, vs. LC-Plasma: Symptom positive 36, Symptom negative 301; days; p = 0.032). Moreover, the cumulative days of fatigue were significantly fewer in the LC-Plasma group (Placebo: Symptom positive 128, Symptom negative 182, vs. LC-Plasma: Symptom positive 110, Symptom negative 225; days; p = 0.032). Markers of muscle damage and stress markers were not significantly different between groups. CONCLUSION: We consider that heat-killed LC-Plasma supplementation relieves morbidity and symptoms of URTI via activation of pDC and decreases fatigue accumulation during consecutive high intensity exercise in athletes. However, LC-Plasma ingestion did not affect markers of muscle damage and stress. TRIAL REGISTRATION: UMIN-CTR, UMIN000020372 . Registered 28 December 2015.

Safety and effectiveness of etanercept for treatment of juvenile idiopathic arthritis: Results from a postmarketing surveillance.

OBJECTIVES: The objectives of this surveillance were to determine safety and effectiveness of etanercept in patients with juvenile idiopathic arthritis (JIA). METHODS: In this postmarketing surveillance, patients aged 5-16 years with active polyarthritis JIA were treated with etanercept at the doses approved in the Japanese package insert. The occurrence and seriousness of adverse events (AEs) were assessed using the Japanese Medical Dictionary for Regulatory Activities version 15.1. Effectiveness was determined as the improvement from baseline in disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR), remission, and physician's assessment of overall improvement. The number of responders was expressed as a percentage. The last observation carried forward method was used to impute missing data. RESULTS: Safety analysis included 102 patients; 22 patients experienced 36 treatment-related AEs, three of which were unexpected. None of the AEs were deemed to need special safety warnings. Effectiveness analysis included 87 patients. At 24 weeks, 29/46 (63.0%) patients demonstrated either good or moderate response in DAS28-4/ESR and treatment was assessed to be markedly effective or effective by physicians in 79/83 (95.2%) patients. CONCLUSIONS: These data are consistent with earlier reports showing that etanercept was effective and demonstrated no safety signals in patients with JIA.

The Effect of L-Ornithine on the Phosphorylation of mTORC1 Downstream Targets in Rat Liver.

A non-protein amino acid, L-ornithine (Orn), has been shown to stimulate the urea cycle and tissue protein synthesis in the liver. The purpose of the current study was to assess whether Orn affects the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) pathway, which is involved in protein synthesis. Primary cultured cells isolated from Wistar rat liver were incubated in an amino acid-free medium, followed by addition of Orn for 3 h. The cell lysate was subjected to immunoblotting to evaluate the phosphorylation of downstream targets of mTORC1, including p70S6K, S6, and 4EBP1. To assess the involvement of mTORC1 for the effect of Orn, the cells were pretreated with the mTOR inhibitor rapamycin before the addition of Orn and the cell lysate was subjected to immunoblotting. We next examined whether the effects of Orn were exerted in vivo. Orn was orally administered to 18 h food-deprived rats, the blood and the livers were collected at 1 and 3 h after administration for immunoblotting. Orn treatment for primary cultured cells for 3 h enhanced the phosphorylation of p70S6K, S6, and 4EBP1. In addition, rapamycin blocked the effects of Orn completely (p70S6K and S6) or partially (4EBP1). The oral administration of Orn to the rat also augmented the phosphorylation of mTORC1 downstream targets notably in S6 at 1 h. Our findings demonstrate that Orn has the potential to induce the phosphorylation of downstream targets of mTORC1 in the rat liver. This may be mediated by the augmentation of mTORC1 activity.

Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers.

BACKGROUND: L-ornithine is a non-essential, non-protein amino acid. Although L-ornithine is contained in various foods, the amount is usually small.Recently, studies have shown that orally administered L-ornithine reduced the stress response in animals.From these findings, we speculated that L-ornithine may play a role in the relieve of stress and improve sleep and fatigue symptoms in humans. Through a randomised, double-blind, placebo-controlled clinical study, we asked if L-ornithine could be beneficial to stress and sleep in healthy workers. METHOD: Fifty-two apparently healthy Japanese adults who had previously felt slight stress as well as fatigue were recruited to be study participants and were randomly divided into either the L-ornithine (400 mg/day) or placebo group. They orally consumed the respective test substance every day for 8 weeks. Serum was collected for the assessment of cortisol and dehydroepiandrosterone-sulphate (DHEA-S). Perceived mood and quality of sleep were measured by the Profile of Mood States (POMS), Athens Insomnia Scale (AIS), and Ogri-Shirakawa-Azumi sleep inventory MA version (OSA-MA). RESULTS: Serum cortisol levels and the cortisol/DHEA-S ratio were significantly decreased in the L-ornithine group in comparison with the placebo group. Also, anger was reduced and perceived sleep quality was improved in the L-ornithine group. CONCLUSION: L-ornithine supplementation has the potential to relieve stress and improve sleep quality related to fatigue, both objectively and subjectively.

The combined effect of caffeine and ornithine on the mood of healthy office workers.

Caffeine is widely consumed and well known for stimulating the central nervous system. When developing new foods and beverages that contain caffeine, it is important to explore the potential synergistic effects of consuming amino acids and other food ingredients with caffeine on humans. Given the physiological pathways affected by the amino acid ornithine, consumption of ornithine with caffeine may have synergistic effects. The purpose of the present study was to examine the effect of consuming caffeine with ornithine in humans. The study used a randomized, placebo-controlled, double-blinded crossover design. The subjects were all healthy office workers who ingested the placebo, 100 mg caffeine, or 100 mg caffeine plus 200 mg ornithine in the morning and completed questionnaires about their mood. Office workers who consumed the combination of caffeine and ornithine had higher mood ratings 8 h after consumption than office workers who consumed caffeine alone. The results of the present study suggest that there is a unique synergistic effect between caffeine and ornithine on the mood of healthy office workers and that ornithine may potentiate the effects of caffeine.

A randomized, double-masked, placebo-controlled crossover trial on the effects of L-ornithine on salivary cortisol and feelings of fatigue of flushers the morning after alcohol consumption.

BACKGROUND: Residual alcohol effects on physiological and psychological symptoms are commonly experienced the morning after alcohol consumption. The purpose of this study was to assess the effects of L-ornithine on subjective feelings and salivary stress markers the morning after alcohol consumption and to investigate whether L-ornithine acutely accelerates ethanol metabolism. METHODS: This study had a randomized, placebo-controlled, double-masked crossover design. Subjects were all healthy Japanese adults with the 'flusher' phenotype for alcohol tolerance. In experiment 1, 11 subjects drank 0.4 g/kg body weight alcohol 1.5 h before their usual bedtime. Half an hour after drinking, they ingested either a placebo or 400 mg ornithine. The next morning on awakening, subjects completed a questionnaire containing a visual analog scale (VAS), the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA), and a profile of mood states (POMS) and collected a saliva sample for measurement of salivary stress markers (cortisol, secretory immunoglobulin A, and α-amylase). In experiment 2, placebo or 400 mg ornithine were administrated to 16 subjects both before and after drinking, and the feeling of drunkenness, breath ethanol concentration and one-leg standing time were repeatedly investigated until 180 min after alcohol consumption. RESULTS: There were significant decreases in "awareness", "feeling of fatigue" and "lassitude" VAS scores and in "anger-hostility" and "confusion" POMS scores and a significant increase in "sleep length" in the OSA-MA test. Salivary cortisol concentrations on awakening were reduced after ornithine supplementation. There were no differences between ornithine and placebo in any of the subjective or physiological parameters of acute alcohol metabolism. CONCLUSIONS: Taking 400 mg ornithine after alcohol consumption improved various negative feelings and decreased the salivary stress marker cortisol the next morning. These effects were not caused by an increase in acute alcohol metabolism.

LKB1 protein expression in neuroendocrine tumors of the lung.

During a recent investigation of LKB1 gene abnormality in lung lesions, strong expression of LKB1 protein in normal neuroendocrine (NE) cells of the bronchial epithelium was found. Because LKB1 functions as a tumor suppressor gene, the question of whether alteration of LKB1 expression is related to the development of pulmonary NE tumors of various grades was investigated. LKB1 immunohistochemistry was examined in a total of 68 primary pulmonary NE tumors consisting of 30 specimens of small cell lung carcinoma (SCLC), 23 large cell neuroendocrine carcinomas (LCNEC), two atypical carcinoids, and 13 typical carcinoids. Loss or low expression (<20% immunoreactive cells) of LKB1 protein expression was more frequently observed in high-grade NE tumors (SCLC and LCNEC; 45/53, 84.9%) than in typical and atypical carcinoids (3/15; 20%). The difference in LKB1 immunoreactivity between the high-grade NE tumors and the carcinoid group was statistically significant (P < 0.0001). In conclusion, marked reduction of LKB1 expression in high-grade NE tumors of the lung suggests a possible role of LKB1 inactivation in its tumorigenesis. Although a few previous studies indicated rare genetic alterations of LKB1 in SCLC, further studies including analysis of other NE tumors and focusing on epigenetic abnormalities of LKB1 gene are warranted.

Role of the PI3K/Akt, mTOR, and STK11/LKB1 pathways in the tumorigenesis of sclerosing hemangioma of the lung.

Although the histogenesis of sclerosing hemangioma (SH) of the lung is now thought to be respiratory epithelial in origin, the genetic abnormalities that mediate its development are not known. Because pathophysiology of several syndromes associated with benign tumors may converge on the tuberous sclerosis complex (TSC), serine/threonine kinase 11 (STK11), and mammalian target of rapamycin (mTOR) pathways, the purpose of the present paper was to investigate their roles in the development of SH. Semiquantitative immunohistochemical analysis was done to assess the expression of phospho-mTOR, phospho-S6 ribosomal protein, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phospho-Akt, STK11, tuberin, hamartin, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1alpha (HIF-1alpha) in 19 cases of typical SH. To determine whether genetic alteration of STK11 is involved in the development of SH, all encoding exons of STK11 were analyzed by polymerase chain reaction (PCR) amplification and direct sequencing of genomic DNA of six specimens. The six specimens were also investigated for whether promoter hypermethylation exists as an alternative inactivating mechanism for STK11. All specimens showed moderate to marked reaction to phospho-S6 ribosomal protein and PTEN; 16 specimens (84%) showed slight to moderate reaction to phospho-mTOR, negative reaction to STK11, and slight to moderate reaction to hamartin; 11 (58%) showed slight to moderate reaction to phospho-Akt; 18 (95%) showed slight to moderate reaction to tuberin and positive reaction for HIF-1alpha; and 17 (90%) showed moderate reaction to VEGF. No somatic mutation of STK11 was found and the six specimens were unmethylated in the promoter region. These data imply that aberrant mTOR signaling may play a role in the development of SH, and its vascular nature may be due partially to high levels of VEGF caused by dysregulation of mTOR signaling.

Risk factors and independent predictors of survival in patients with pulmonary epithelioid haemangioendothelioma. Review of the literature and a case report.

Pulmonary epithelioid haemangioendothelioma (PEH) is a rare pulmonary neoplasm. A patient with PEH with lymph node and pleural metastases that were discovered incidentally is described. An abnormal left upper lobe shadow was noticed on CXR in a 70-year-old woman during an assessment for the sudden onset of nausea and vomiting. Transbronchial lung biopsy did not provide a diagnosis. Lobectomy and lymph node resection were performed. The histological diagnosis of PEH was confirmed immunohistochemically by positive reactions to factor VIII-related antigen and CD34. Data on 93 patients with PEH including the present case report were analysed by Cox regression analysis using forward stepwise method to identify the risk factors, and the independent predictors of survival in patients with PEH. It revealed that male, symptomatic patients, presence of cough, haemoptysis, chest pain, multiple unilateral nodules, pleural effusion, metastases to more than one site and lymph node metastases were all significant risk factors for PEH (P<0.05). Symptomatic patients and presence of pleural effusion were the independent predictors of survival in patients with PEH.

Metastatic germ cell tumor of the lung masquerading as primary rhabdomyosarcoma.

Two years after testicular resection was carried out in a 40-year-old man that revealed mixed germ cell tumor of more than one histological type (seminoma, embryonal cell carcinoma, and yolk sac tumor), he presented with an asymptomatic pulmonary nodule in his left lower lobe. Video-assisted thoracoscopic partial resection of the tumor revealed a 24 x 20 mm teratoma with somatic-type malignancy in which pleomorphic rhabdomyosarcoma was a major element. One year later, asymptomatic tumor recurrence occurred at both edges of the stapler line as 22 x 20 mm and 10 x 5 mm nodules composed only of pleomorphic rhabdomyosarcoma. Throughout the course there was no abdominal lymph node swelling detected by computed tomography (CT) and tumor markers were normal. Adjuvant chemotherapy was started after the tumor recurrence. Currently, the patient is still undergoing chemotherapy 5 months after the tumor recurrence. In conclusion, despite the fact that primary pulmonary rhabdromyosarcoma is a rare neoplasm, metastatic pulmonary germ cell tumor with somatic-type malignancy showing predominantly rhabdomyosarcomatous differentiation should be considered in the differential diagnosis of such lesions of the lung.

An oxygen transporter hemocyanin can act on the late pathway of melanin synthesis.

5,6-Dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) are precursors of eumelanin. The effects of crustacean hemolymph proteins on these eumelanin-related metabolites were investigated. Zymogram analysis indicated that polymers of hemocyanin (Hc) subunits converted DHI into black pigment while no effects were observed using DHICA as a substrate. Spectrum changes for mixtures of purified Hc and DHI showed a profile similar to oxidized DHI by mushroom tyrosinase while Hc had only slight effects on DHICA. Typical inhibitors of tyrosinase and phenoloxidase severely hampered the production of oxidized DHI. Taken together with previous results, these data indicate that Hc plays a crucial role in the conversion of DHI in the hemolymph of crustaceans, which promotes late reactions in the melanin synthetic pathway as well as early reactions (oxidation of tyrosine and DOPA to dopaquinone).