Comprehensive expression analysis of hormone-like substances in the subcutaneous adipose tissue of the common bottlenose dolphin Tursiops truncatus.

Marine mammals possess a specific subcutaneous fat layer called blubber that not only insulates and stores energy but also secretes bioactive substances. However, our understanding of its role as a secretory organ in cetaceans is incomplete. To exhaustively explore the hormone-like substances produced in dolphin subcutaneous adipose tissue, we performed seasonal blubber biopsies from captive female common bottlenose dolphins (Tursiops truncatus; N = 8, n = 32) and analyzed gene expression via transcriptomics. Analysis of 186 hormone-like substances revealed the expression of 58 substances involved in regulating energy metabolism, tissue growth/differentiation, vascular regulation, immunity, and ion/mineral homeostasis. Adiponectin was the most abundantly expressed gene, followed by angiopoietin protein like 4 and insulin-like growth factor 2. To investigate the endocrine/secretory responses of subcutaneous adipose tissue to the surrounding temperature, we subsequently compared the mean expression levels of the genes during the colder and warmer seasons. In the colder season, molecules associated with appetite suppression, vasodilation, and tissue proliferation were relatively highly expressed. In contrast, warmer seasons enhanced the expression of substances involved in tissue remodeling, immunity, metabolism, and vasoconstriction. These findings suggest that dolphin blubber may function as an active secretory organ involved in the regulation of metabolism, appetite, and tissue reorganization in response to changes in the surrounding environment, providing a basis for elucidating the function of hormone-like substances in group-specific evolved subcutaneous adipose tissue.

Association of seasonal changes in circulating cortisol concentrations with the expression of cortisol biosynthetic enzymes and a glucocorticoid receptor in the blubber of common bottlenose dolphin.

Cortisol is secreted from the adrenal cortex in response to stress, and its circulating levels are used as robust physiological indicators of stress intensity in various animals. Cortisol is also produced locally in adipose tissue by the conversion of steroid hormones such as cortisone, which is related to fat accumulation. Circulating cortisol levels, probably induced by cold stress, increase in cetaceans under cold conditions. However, whether cortisol production in subcutaneous adipose tissue is enhanced when fat accumulation is renewed during the cold season remains unclear. Therefore, in this study, we examine the effect of environmental temperature on the expression of cortisol synthesis-related enzymes and a glucocorticoid receptor in the subcutaneous fat (blubber) and explore the association between these expressions and fluctuations in circulating cortisol levels in common bottlenose dolphins (Tursiops truncatus). Skin biopsies were obtained seasonally from eight female dolphins, and seasonal differences in the expression of target genes in the blubber were analyzed. Blood samples were collected throughout the year, and cortisol levels were measured. We found that the expressions of cytochrome P450 family 21 subfamily A member 2 (CYP21A2) and nuclear receptor subfamily 3 group C member 1 (NR3C1), a glucocorticoid receptor, were increased in the cold season, and 11 beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) showed a similar trend. Blood cortisol levels increased when the water temperature decreased. These results suggest that the conversion of 17-hydroxyprogesterone to cortisol via 11-deoxycortisol and/or of cortisone to cortisol is enhanced under cold conditions, and the physiological effects of cortisol in subcutaneous adipose tissue may contribute to on-site lipid accumulation and increase the circulating cortisol concentrations. The results obtained in this study highlight the role of cortisol in the regulation of the blubber that has developed to adapt to aquatic life.

Seasonal changes in circulating gonadal steroid levels and physiological evidence for the presence of intrinsic circannual reproductive cycles in captive finless porpoises Neophocaena asiaeorientalis from the western Inland Sea, Japan.

We monitored annual fluctuations of gonadal steroid levels in three sexually mature captive finless porpoises (Neophocaena asiaeorientalis; two males and one female) from two different facilities over 56-91 months. Two animals (one male and one female) were held in an indoor tank with a sunroof (facility A) and the other male was held in an indoor tank without a sunroof (facility B). Water temperatures in both facilities reflected seasonal changes during the study period with a minor difference in the fluctuation pattern. Testosterone levels of the male in facility A were higher from spring to summer every year and exhibited a 12-month cycle. The female showed estrus cycles in 1-month intervals from summer to winter, excluding 2 anestrus years. In contrast, the period of higher testosterone levels of the male in facility B gradually initiated earlier over the years under a constant photoperiod (11.5L:12.5D) and exhibited a 9-month cycle during the first 52 months. After changing the light conditions to a natural photoperiod, its testosterone levels were high from early spring to summer for 3 consecutive years and exhibited a 12-month cycle. Our results showed that under a constant artificial photoperiod, the male in facility B failed to recognize the seasonal changes of a natural external environment, resulting in a 9-month, free-running hormone cycle.

Differences in the effects of Asian dust on pulmonary function between adult patients with asthma and those with asthma-chronic obstructive pulmonary disease overlap syndrome.

BACKGROUND: Asian dust (AD) exposure exacerbates pulmonary dysfunction in patients with asthma. Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS), characterized by coexisting symptoms of asthma and chronic obstructive pulmonary disease, is considered a separate disease entity. Previously, we investigated the effects of AD on pulmonary function in adult patients with asthma. Here, we present the findings of our further research on the differences in the effects of AD exposure on pulmonary function between patients with asthma alone and those with ACOS. METHODS: Between March and May 2012, we conducted a panel study wherein we monitored daily peak expiratory flow (PEF) values in 231 adult patients with asthma. These patients were divided into 190 patients with asthma alone and 41 patients with ACOS in this study. Daily AD particle levels were measured using light detection and ranging systems. Two heavy AD days (April 23 and 24) were determined according to the Japan Meteorological Agency definition. A linear mixed model was used to estimate the association between PEF and AD exposure. RESULTS: Increments in the interquartile range of AD particles (0.018 km(-1)) led to PEF changes of -0.50 L/min (95% confidence interval, -0.98 to -0.02) in patients with asthma alone and -0.11 L/min (-0.11 to 0.85) in patients with ACOS. The PEF changes after exposure to heavy AD were -2.21 L/min (-4.28 to -0.15) in patients with asthma alone and -2.76 L/min (-6.86 to 1.35) in patients with ACOS. In patients with asthma alone, the highest decrease in PEF values was observed on the heavy AD day, with a subsequent gradual increase over time. CONCLUSION: Our results suggest that the effects of AD exposure on pulmonary function differ between patients with asthma alone and ACOS, with the former exhibiting a greater likelihood of decreased pulmonary function after AD exposure.

Association between pulmonary function and daily levels of sand dust particles assessed by light detection and ranging in schoolchildren in western Japan: A panel study.

BACKGROUND: An important aspect of sand dust emissions in association with respiratory disorders is the quantity of particulate matter. This is usually expressed as particulate matter less than 10 µm (PM10) and 2.5 µm (PM2.5). However, the composition of PM10 and PM2.5 varies. Light detection and ranging is used to monitor sand dust particles originating in East Asian deserts and distinguish them from air pollution aerosols. The objective of this study was to investigate the association between the daily levels of sand dust particles and pulmonary function in schoolchildren in western Japan. METHODS: In this panel study, the peak expiratory flow (PEF) of 399 schoolchildren was measured daily from April to May 2012. A linear mixed model was used to estimate the association of PEF with the daily levels of sand dust particles, suspended particulate matter (SPM), and PM2.5. RESULTS: There was no association between the daily level of sand dust particles and air pollution aerosols, while both sand dust particles and air pollution aerosols had a significant association with SPM and PM2.5. An increment of 0.018 km(-1) in sand dust particles was significantly associated with a decrease in PEF (-3.62 L/min; 95% confidence interval, -4.66 to -2.59). An increase of 14.0 µg/m(3) in SPM and 10.7 µg/m(3) in PM2.5 led to a significant decrease of -2.16 L/min (-2.88 to -1.43) and -2.58 L/min (-3.59 to -1.57), respectively, in PEF. CONCLUSIONS: These results suggest that exposure to sand dust emission may relate to pulmonary dysfunction in children in East Asia.

Association of Sand Dust Particles with Pulmonary Function and Respiratory Symptoms in Adult Patients with Asthma in Western Japan Using Light Detection and Ranging: A Panel Study.

Light detection and ranging (LIDAR) can estimate daily volumes of sand dust particles from the East Asian desert to Japan. The objective of this study was to investigate the relationship between sand dust particles and pulmonary function, and respiratory symptoms in adult patients with asthma. One hundred thirty-seven patients were included in the study. From March 2013 to May 2013, the patients measured their morning peak expiratory flow (PEF) and kept daily lower respiratory symptom diaries. A linear mixed model was used to estimate the correlation of the median daily levels of sand dust particles, symptoms scores, and PEF. A heavy sand dust day was defined as an hourly concentration of sand dust particles of >0.1 km(-1). By this criterion, there were 8 heavy sand dust days during the study period. Elevated sand dust particles levels were significantly associated with the symptom score (0.04; 95% confidence interval (CI); 0.03, 0.05), and this increase persisted for 5 days. There was no significant association between PEF and heavy dust exposure (0.01 L/min; 95% CI, -0.62, 0.11). The present study found that sand dust particles were significantly associated with worsened lower respiratory tract symptoms in adult patients with asthma, but not with pulmonary function.

Difference of health-care associated pneumonia between large hospitals and small hospitals in Japan.

OBJECTIVE: Health-care associated pneumonia (HCAP) is a new category of pneumonia. We investigated differences of epidemiology, pathogens, and outcomes between HCAP patients in large hospitals and those in small hospitals. METHODS: This was a retrospective observational study of patients hospitalized with HCAP from December 2009 to March 2010. HCAP was defined according to ATS/IDSA criteria. A large hospital was defined as ≥ 200 beds and a small hospital was <200 beds. RESULTS: Of 117 patients, 61 patients were admitted to large hospitals and 56 patients were admitted to small hospitals. There was a significant difference of HCAP diagnostic criteria between the two groups. The A-DROP severity class was worse in the large hospital group than the small hospital group (P<0.05). Respiratory failure and disturbance of consciousness were more frequent in the large hospital group (P<0.05). The mortality rate was 8.2% in the large hospital group versus 1.8% in the small hospital group. Patients in the very severe A-DROP class had a high mortality rate of 33% in both groups. CONCLUSION: Patients with severe HCAP were more likely to be admitted to large hospitals. Patients in the very severe A-DROP class should receive intensive antibiotic therapy, but not all patients need broad-spectrum therapy.

Correlation between Asian dust storms and worsening asthma in Western Japan.

BACKGROUND: Severe wind storms during spring in East Asia, called Asian dust storms (ADS), have been assessed in the past for their effect on health in Asian countries. Our objective was to study the ADS association with asthma symptoms in adult patients in Japan. METHODS: We designed a telephone survey to assess ADS influence on upper and lower respiratory, ocular and cutaneous symptoms in 98 patients with adult asthma from April to May 2007. Peak expiratory flow (PEF) was also measured from February to May. RESULTS: Worsening lower respiratory symptoms were noted by 22 of 98 patients during ADS in April, when Japanese cedar pollen levels also increased. During ADS in May, however, Japanese cedar and cypress pollen levels were not elevated, 11 patients had worsening of lower respiratory symptoms. None required emergency treatment for the exacerbation. Lower respiratory symptoms worsening most were cough and sputum; this was more common in patients with allergic rhinitis or atopy than in those without (P < 0.05). Min%Max differed significantly at 88.7 ± 6.6% during dust dispersion period, defined as the ADS day plus the next 6 days, versus 92.0 ± 5.3% during the 7-day period before a dust storm. CONCLUSIONS: We found that ADS aggravated lower respiratory symptoms in adult patients with asthma, but this influence was mild.

Bronchial artery embolization before interventional bronchoscopy to avoid uncontrollable bleeding: a case report of endobronchial metastasis of renal cell carcinoma.

Extreme caution should be taken to avoid uncontrollable bleeding in treating hypervascular tumors via bronchoscope. We report two cases of endobronchial metastasis of renal cell carcinoma treated with bronchial artery embolization (BAE) before endoscopic treatments. The intraluminal lesions were removed swiftly and safely. Although arterial embolization is not always efficacious in cases of tracheal lesions, BAE is effective for tumors located in the carina, bilateral main bronchus or intermediate bronchus. The addition of BAE before endoscopic tumor removal should be considered a treatment option in patients suffering from airway obstructions due to hypervascular tumors such as renal cell carcinoma.

[Acute bird-related hypersensitivity pneumonitis: radiological findings in a case in the early phase after onset].

A 71-year-old woman was admitted to our hospital four times because of high fever and dyspnea from September to November in 2007. We treated her with antibiotics on her first two admissions. HOwever, we suspected hypersensitivity pneumonitis on the third admission because she suffered from fever and dyspnea soon after she had been discharged and returned home. She recovered only with the oxygen therapy on the last two admissions. Computed tomography of the chest showed early phase localized consolidation but changed to ground-glass opacities spreading over the entire lung field later during her third and fourth admissions. Bronchial alveolar lavage showed increases in total cell count, lymphocytes and IgA of pigeon-dropping extracts' and budgerigar-dropping extracts. TBLB showed epithelioid cell granulomas without caseous necrosis and alveolar septal inflammation. Inhalation challenge test using freeze-dried pigeon-dropping extracts was positive, therefore we finally established a diagnosis of acute bird related hypersensitivity pneumonitis. This is apparently the first report of acute bird-related hypersensitivity pneumonitis showing localized consolidation initially and later changing to diffuse ground-glass opacities. These radiological observations are significant in considering the onset and the progression of this disease.

Lung cancer arising in association with middle lobe syndrome.

Middle lobe syndrome, caused mainly by benign inflammatory diseases, such as chronic bronchitis and bronchiectasis, is manifested clinically as a chronic cough with sputum production. The prognosis associated with this syndrome is considered good in most cases which are caused by chronic inflammatory diseases. A patient who developed lung cancer in the course of long-term treatment for right middle lobe syndrome is described. A 63-year-old woman was admitted to our hospital with complaints of right iliac bone pain. She had been treated for chronic bronchitis and bronchiectasis associated with middle lobe syndrome for 16 years before admission. Work-up of a lung adenocarcinoma originating from the right middle lobe disclosed bone metastasis to the illium. Tumorigenesis in association with middle lobe syndrome has not yet been reported, but this first reported case suggests the need to be alert to the possibility.

[A case of primary pulmonary hypertension treated by long-term continuous administration of epoprostenol].

A 50-year-old man was urgently transferred to another hospital due to unconsciousness diagnosed as due to primary pulmonary hypertension following cardiac catheter test and pulmonary blood flow scintigraphy. He was referred to our hospital for treatment of hypoxemia. Thereafter, he was treated by home oxygen therapy and home epoprostenol therapy, although he required frequent admissions. During treatment, problems consisting of self-evulsion and infection of the insertion site occurred. Changes in symptoms, arterial blood gas analysis, serum BNP and ultracardiography were useful for managing home epoprostenol therapy. We reported a case of primary pulmonary hypertension treated by long-term continuous administration of epoprostenol for about 6 years and 9 months.

[Case with double primary cancers occurring synchronously in both the lung and jejunum diagnosed according to TTF-1 expression].

A 47-year-old man was diagnosed as having adenocarcinoma of the lung (T4N0M0) in August 2002. He received chemotherapy and radiotherapy. In June 2003, he complained of lower abdominal pain with palpable mass in the left lower abdomen. On abdominal CT, we recognized a mass measuring 50 mm, which we considered a mesenteric lymph node. As the mass gradually grew and pain increased, we performed lymph node resection. The lymph node was near by the Treitz' ligament, and a tumor measuring 30 mm was observed in the jejunum. Therefore, we performed jejunectomy. Pathological examination of the lesion demonstrated adenocarcinoma. The differential diagnosis between small intestine metastasis and primary small intestine cancer was difficult. As adenocarcinoma of the jejunum was negative for TTF-1 in immunohistochemical staining and adenocarcinoma of the lung was positive, we diagnosed this patient as having primary jejunal cancer. We report this rare case of double cancer involving the lung and jejunum.

[The clinical features of ultra-old tuberculosis patients in our hospital].

PURPOSE: To examine the clinical features of ultra-old patients over 85 years of age who were admitted to our hospital for tuberculosis treatment. METHODS: Clinical features of tuberculosis patients over 85 years of age who were admitted to our hospital from January, 1996 to May, 2003 were analyzed in relation to their disease status, complications and prognosis. RESULTS: They showed a high tuberculin negative rate (26.2%) and a low rate of cavity formation (21.8%), and the smear positive rate of tubercle bacilli was not high (51.2%). As to the complications, cerebrovascular disorders were overwhelmingly high (62.2%) and the death rate due to side effects of drugs was high. The sputum smear positive rate was higher (70%) among patients from nursing home. CONCLUSION: The diagnosis of tuberculosis was often delayed with high mortality rate due to side effects of drugs among ultra-old patients and tuberculosis infection control measures to contacts are often needed.

[A case of M. fortuitum lung disease with small-cell lung cancer].

A 58-year-old man was admitted to our hospital because of an abnormal shadow found on chest radiography. Chest radiographs and chest CT on admission showed a bulla with a niveau and infiltration in the right upper lobe. Smear of sputum and bronchial lavage were negative for acid-fast bacilli. Despite treatment with meropenem and clindamycin, the infiltrating shadow worsened. Since bronchial lavage and sputum culture were positive for M. fortuitum, these drugs were replaced with minocycline and imipenem. Thereafter, the shadow on the chest radiograph improved. After discharge, outpatient treatment with clarithromycin and levofloxacin was continued. After 4 months, the residual tumor shadow in the right upper lobe gradually grew. When a CT-guided transcutaneous needle lung biopsy was undertaken, malignant cells were found. Right upper lobectomy was performed. Pathological examination of the lesion demonstrated small-cell lung cancer. If a lesion does not change after nontuberculous mycobacteria treatment, the physician should consider other lesions such as lung cancer.

[The usefulness of lymphocyte stimulation test (LST) in side effects of antituberculosis drugs].

PURPOSE: The usefulness of the lymphocyte stimulation test (LST) was examined in patients who arose side effects to antituberculosis drugs. METHODS: The usefulness of LST was examined in 36 patients from January, 1999 to July, 2002. RESULTS: There were 11 LST positive patients, and the LST positive rate was 30.6%. The causing agents determined by the LST positive patients were INH in 7, RFP in 3 and EB in one. The sensitivity of LST was 46.2% and the specificity of LST was 76.6%. CONCLUSION: LST positive rate of antituberculosis drugs was low and it was difficult to determine the causing drugs by LST.