Adrenal dysplasia in a young SD rat.

The present report describes an adrenal dysplasia in which developmental abnormality was observed in the adrenal gland of a six-week-old male Crl:CD(SD) rat. Microscopically, a localized lesion composed of mildly vacuolated adrenal fasciculata cells with a slightly disturbed cord structure and containing areas with high cell density was observed in a unilateral adrenal gland; no macroscopical changes were detected in the organ. The areas with high cell density consisted of two cell types. One type included small cells with a round nucleus and acidophilic cytoplasm, and the cells were positive for steroidogenic factor-1 (SF-1) but negative for nestin. The other type of cells had a spindle to polygonal shape, clear nucleus, and a cytoplasm with an obscure boundary; the cells were positive for nestin but negative for SF-1, neuronal nuclear antigen, and chromogranin A. These results suggested that the former type of cells were adrenal cortex cells and that the latter were immature neuronal cells. Considering that immature adrenal cortex cells and neural crest cells (future adrenal medulla) are mixed during a stage in rat adrenal gland development, we concluded that the observed lesion was caused by developmental abnormality. To the best of our knowledge, this is the first report to describe dysplasia in rat adrenal glands.

Cutaneous mastocytosis with a mutation in the juxtamembrane domain of c-kit in a young laboratory beagle dog.

Cutaneous mastocytosis, which resembles a subset of urticaria pigmentosa in humans, is rare in dogs. We herein report unrepresentative neoplastic proliferation of mast cells in ventral skin removed routinely from a nine-month-old female laboratory beagle dog at necropsy. A histological examination revealed diffuse extensive cellular infiltration from the superficial to deep dermis in most parts of the skin around the fourth and fifth mammary papilla without nodule formation. Tumor cells were fairly monomorphic, well-differentiated mast cells with round nuclei of small distinct nucleoli and moderate to abundant, slightly eosinophilic and granular cytoplasm. A perivascular arrangement of mast cells was noted at the margin of the lesions. Infiltration of eosinophils and degeneration of collagen were not observed in the dermis. Cutaneous mastocytosis was diagnosed based on these features. A sequence analysis of lesions revealed the deletion of Gln555 to Ile570 within the juxtamembrane domain of c-kit (exon 11).

Screening of lactic acid bacteria that can form mixed-species biofilm with Saccharomyces cerevisiae.

The abilities of lactic acid bacteria (LAB) to form mixed-species biofilm with Saccharomyces cerevisiae in a static co-culture were investigated out of 168 LAB stock cultures, and two Lactobacillus plantarum strains (D71 and E31) and one Leuconostoc mesenteroides strain K01 were found to form mixed-species biofilm with S. cerevisiae BY4741. SEM observation showed that there was no significant difference in morphological properties among these three mixed-species biofilms and they resembled that formed by S. cerevisiae with L. plantarum ML11-11 previously isolated from a brewing sample of Fukuyama pot vinegar. The co-aggregation assays showed that L. plantarum D71 and L. plantarum E31 could co-aggregate with S. cerevisiae similarly to L. plantarum ML11-11, while L. mesenteroides K01 had no ability to co-aggregate with yeast. The above results indicate that aggregation followed by direct cell-to-cell contact is required for mixed-species biofilm formation between these L. plantarum strains and S. cerevisiae, though some different mechanism may be involved in biofilm formation between L. mesenteroides strain and S. cerevisiae.

FGF-2 angiogenesis in bone regeneration within critical-sized bone defects in rat calvaria.

OBJECTIVE: This study examined the effect of basic fibroblast growth factor (FGF)-2 with an absorbable collagen sponge on angiogenesis and bone regeneration in rat calvarial critical-sized bone defects using microcomputed tomography. METHODS: Forty 7-week-old male Fischer rats were used. The symmetrical critical-sized calvarial bone defects (5 mm diameter) were created. An absorbable collagen sponge with or without FGF-2 (0.1% or 0.3%) was implanted into each bone defect. RESULTS: Blood vessel and bone volumes were significantly higher in the 0.3% FGF-2 group compared with the control and 0.1% FGF-2 groups on day 28. Significantly more osteoblast- and osteoclast-like cells were seen in the 0.3% FGF-2 group. CONCLUSIONS: Thus, FGF-2 increased blood vessel and bone formation in rat calvarial critical-sized bone defects.

Community-based system, reports, and substantiated cases of elder abuse: disparities between municipalities and relating factors in Japan.

This study examines (1) the staffing and financial characteristics of systems for elder abuse detection and intervention in the municipal governments of Japan and (2) the relationship among the development of detection and intervention systems, the reporting rates of suspected elder abuse cases, and substantiated abuse rates in 927 municipalities across Japan. Progressive systems for the detection and intervention of elder abuse were significantly associated with a larger number of public officers than in non-progressive systems. Furthermore, greater rates of both suspected and substantiated cases of abuse were associated with progressive systems for elder abuse detection and intervention. Per capita annual expenditures on the comprehensive support project and the community general support center's catchment under the Long-Term Care Insurance (LTCI) program showed no significant association with the development of systems, the rate of suspected cases, or the number of substantiated cases. National social policy makers should examine strategies that would help municipalities assign sufficient staff to elder abuse detection and intervention programs.

Acsl1 is essential for skin barrier function through the activation of linoleic acid and biosynthesis of ω-O-acylceramide in mice.

The long-chain acyl-CoA synthase1 (Acsl1) is a major enzyme that converts long-chain fatty acids to acyl-CoAs. The role of Acsl1 in energy metabolism has been elucidated in the adipose tissue, heart, and skeletal muscle. Here, we demonstrate that systemic deficiency of Acsl1 caused severe skin barrier defects, leading to embryonic lethality. Acsl1 mRNA and protein are expressed in the Acsl1+/+ epidermis, which are absent in Acsl1-/- mice. In Acsl1-/- mice, epidermal ceramide [EOS] (Cer[EOS]) containing ω-O-esterified linoleic acid, a lipid essential for the skin barrier, was significantly reduced. Conversely, ω-hydroxy ceramide (Cer[OS]), a precursor of Cer[EOS], was increased. Moreover, the levels of triglyceride (TG) species containing linoleic acids were lower in Acsl1-/- mice, whereas those not containing linoleic acid were comparable to Acsl1+/+ mice. As TG is considered to work as a reservoir of linoleic acid for the biosynthesis of Cer[EOS] from Cer[OS], our results suggest that Acsl1 plays an essential role in ω-O-acylceramide synthesis by providing linoleic acid for ω-O-esterification. Therefore, our findings identified a new biological role of Acsl1 as a regulator of the skin barrier.

The effect of emphysema on lung function and survival in patients with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: In this study the prevalence, lung function and prognosis of IPF combined with emphysema were evaluated. METHODS: Consecutive patients with usual interstitial pneumonia (UIP) on high-resolution computed tomography (HRCT), with or without emphysema, were assessed retrospectively. The area of fibrosis in the base of the lungs was assessed by HRCT as minimal (<2 cm from the subpleura), moderate (>or=2 cm from the subpleura, <1/3 of the area of the base of the lungs) or severe (>or=1/3 of the area of the base of the lungs). RESULTS: Among 660 patients with UIP on HRCT, 221 showed upper-lobe emphysema. Pulmonary function results for patients with UIP and UIP/emphysema, respectively, were: FVC, 71.8% and 87.1%; FEV1%, 86.7% and 87.9%; and DL(CO), 74.3% and 65.2% of predicted. The relationship between FVC, the extent of fibrosis and survival was investigated in 362 patients with records of pulmonary function tests and no lung cancer at the time of entry into the study. Although the extent of fibrosis was similar between the groups, 71.3% of UIP patients met the lung volume criteria for IPF (FVC <80% of predicted), whereas only 26.5% of UIP/emphysema patients met the lung volume criteria for IPF. Median survival was 7.5 years in the UIP group and 8.5 years in the UIP/emphysema group. CONCLUSIONS: Emphysema was a common finding in patients with UIP. Patients with UIP and emphysema had greater lung volumes and better survival compared with those with UIP alone.

[Pulmonary mycobacteriosis caused by Mycobacterium peregrinum in a young, healthy man].

A 24-year-old male never-smoker with no contributory medical history was referred to our division because of chronic productive cough and fever. His chest CT showed pulmonary consolidation including nodular shadows around the bronchovascular bundle in both upper lobes and right middle lobe. Sputum smears were negative but cultures were positive for Mycobacterium peregrinum, twice. He was given a diagnosis of pulmonary mycobacteriosis caused by M. peregrinum and treated with clarithromycin, levofloxacin, and ethambutol. His symptoms and the infiltrates improved, and further sputum cultures were negative for mycobacteria. M. peregrinum is a species included in the M. fortuitum group, of rapidly-growing non-tuberculous mycobacteria. To the best of our knowledge, only 2 cases with lung infection caused by M. peregrinum have been previously reported, both of which occurred in patients in their 60s with underlying diseases, including low immunity due to immunosuppressants for polymyositis, or bronchiectasia. We describe a rare case of pulmonary mycobacteriosis due to M. peregrinum in a healthy man without any underlying diseases.

[Clinical features of pneumothorax in patients with active nontuberculous mycobacterial lung disease].

UNLABELLED: This study was retrospectively conducted to clarify the clinical features of pneumothorax in patients with active nontuberculous mycobacterial (NTM) lung disease. The patients were 9 men and 7 women, with a median age of 70. Pathogenic mycobacteria were 12 Mycobacterium avium complex, 2 Mycobacterium kansasii, and 2 Mycobacterium fortuitum. More than one lung field was affected by NTM disease in 11 patients, whereas 4 patients were given a diagnosis of mild NTM disease only at the onset of pneumothorax. Five patients recovered with rest only, 4 with thoracic drainage, 4 needed surgery, and 2 developed chronic pneumothorax. Five patients experienced more than one recurrence of pneumothorax during treatment for NTM disease. The rate of the complication of pneumothorax in patients with NTM lung disease was estimated at around 2.3%. CONCLUSION: Pneumothorax associated with NTM lung disease is not rare and is sometimes difficult to control.

Nephrotic syndrome induced by dibasic sodium phosphate injections for twenty-eight days in rats.

Sprague-Dawley rats received once daily tail-vein injections of 360 mM dibasic sodium phosphate solution at 8 mL/kg for fourteen or twenty-eight days. Clinical examination revealed persistent proteinuria from three days after the first dosing and thereafter severe proteinuria from eight days or later in the phosphate-treated groups. Proteinuria developed without remission even after fourteen-day withdrawal in the fourteen-day dosed group. Phosphate-treated animals developed lipemia, hypercholesterolemia, anemia, higher serum fibrinogen levels, and lower serum albumin/globulin ratios on day 29. Renal weight increased significantly compared with control animals, and the kidneys appeared pale and enlarged with a rough surface. Histopathologically, glomerular changes consisted of mineralization in whole glomeruli, glomerular capillary dilatation, partial adhesion of glomerular tufts to Bowman's capsule, and mesangiolysis. Ultrastructural lesions such as an increased number of microvilli, effacement of foot processes, and thickening of the glomerular basement membrane, and immunocytochemical changes in podocytes, mainly decreased podoplanin-positive cells and increased desmin expression, were also conspicuous in the phosphate-treated rats for twenty-eight days. Marked tubulointerstitial lesions were tubular regeneration and dilatation, protein casts, mineralization in the basement membrane, focal interstitial inflammation, and fibrosis in the cortex. These clinical and morphological changes were similar to features of human nephrotic syndrome.

[Trends in antibiotic susceptibility and genetic beta-lactam resistance patterns among Haemophilus influenzae cases isolated from adult patients with respiratory tract infection].

Haemophilus influenzae, a major respiratory tract pathogen, is becoming increasingly resistant to beta-lactam antibiotics. Studying annual trends in antibiotic susceptibility and genetic patterns of H. influenzae beta-lactam resistance, we isolated 122 strains from the adult respiratory tract in 2007, determined MIC for different antibiotics, and analyzed TEM-1 beta-lactamase resistant genes and ftsI encoding PBP3 mutation compared to results in 2005 and 2007. We found that ABPC-susceptible strains with MIC <1 microg/mL (BLNAS) accounted for 71.0%, ABPC-resistant strains with MIC exceeding 2 microg/mL without beta-lactamase activity (BLNAR) for 25.3%, and beta-lactamase-positive strains (BLP) for 3.7%. The BLNAS ratio showed no significant change from 2002 and 2005. The BLP ratio decreased from those in 2002 and 2005. Genetic studies of resistant genes showed that gBLNAS with no resistant genes had increased in the last five years. The ratio of all strains with PBP3 mutation (gBLNAR and gLow-BLNAR) remained constant from 2002 to 2007. The proportion of gBLNAR with two PBP3 mutations had increased, however, while gLow-BLNAR with one mutation had decreased. LVFX showed constant strong antimicrobial potency for all mutation groups. Among beta-lactam antibiotics, the lowest MIC90 was observed in parenteral CTRX and oral CDTR-PI use. Although a new MIC peak generated by gBLNAR became obvious in the ABPC and CDTR-PI MIC distribution, the MIC of the new peak was still low enough to treat with high doses of those two antibiotics.

[A case of pulmonary Mycobacterium avium infection presenting multiple nodules with substantial difference in 18F-fluorodeoxyglucose uptake].

A 56-year-old man presented with a chief complaint of chronic cough due to bronchial asthma and pulmonary emphysema in 2001, without any abnormal findings on chest CT. His symptoms improved with high-dose inhaled corticosteroid. In February 2004, multiple nodules without bronchiectasis appeared in the chest CT. Pulmonary Mycobacterium avium infection was diagnosed by bronchial lavage and sputum culture. After multiple nodules appeared and disappeared repeatedly without medication, most nodules vanished after administration of antituberculous drugs. In Feburary 2007, a rapidly growing mass appeared in the right upper lobe, and a new nodule emerged in the left upper lobe the following month. On 18F-fluorodeoxyglucose positron emission tomography (18 FDG-PET), a substantial difference in 18FDG uptake was observed although both lesions were shown to be caused by Mycobacterium avium infection by needle biopsy. The lung specimen of the lesion with high 18FDG uptake demonstrated neutrophil infiltrates, suggesting acute inflammation. On the other hand, neutrophil infiltrates were not observed in the lesion with low uptake. We conclude that the degree of 18FDG uptake is not useful to decide when to initiate therapy and evaluate the efficacy of treatment.

[A case of Ehlers-Danlos syndrome suspected from pulmonary hematoma due to disruption of the lung].

A 20-year-old man was referred to our hospital due to hemoptysis. Chest CT showed a ground-glass opacity, suggesting pulmonary bleeding; however, a diagnosis was not obtained. At a follow-up examination after 2 months, Chest CT showed improvement of the ground-glass opacity, however a cavitary nodule had newly appeared. Four months later, another new nodule was found on chest X-ray film. Video-assisted thoracoscopic lung biopsy was performed for pathological diagnosis; disruption of the pleural, lung and blood vessels, and pulmonary hematoma were found. We thought of the fragility of the pleuro-pulmonary connective tissue and also thought of the probability of Ehlers-Danlos syndrome (EDS). A biochemical analysis of cultured dermal fibroblasts and molecular biological examination revealed decreased production of type III collagen in fibroblasts and COL3A1 mutation. We diagnosed this case as vascular EDS. EDS is one of the differential diagnoses in patients presenting hemoptysis and pulmonary hematoma due to disruption of the lung.

[Usefulness of monitoring plasma voriconazole concentration in patients with chronic necrotizing pulmonary aspergillosis].

We investigated the significance and the usefulness of monitoring plasma voriconazole levels in patients with chronic necrotizing pulmonary aspergillosis associated with underlying chronic respiratory diseases. The average trough level was 2.2 microg/ml and there was no correlation between trough levels and voriconazole doses. Orally administered drug showed no significant difference in trough or peak levels compared with parenteral injection. Six cases with visual adverse events had significantly higher nadirs compared to those without visual disturbance. All three cases who discontinued the drug due to liver dysfunction had plasma trough levels higher than 4.0 microg/ml. Those who failed to respond to the treatment had trough levels lower than 1.4 microg/ml or peak levels lower than 2.8 microg/ml, while some cases with plasma level lower than those levels responded well. Since plasma voriconazole level has a large inter-patient variability, drug monitoring may be beneficial to evaluate the drug efficacy and safety in each individual.

[Case of hot tub lung with confirmation of exacerbation following jet bath use].

A 49-year-old woman presented with exertional dyspnea. Chest CT revealed patchy areas of ground-glass attenuation and ill-defined centrilobular nodules scattered in both lungs. Bronchoalveolar lavage (BAL) fluid showed lymphocytosis. Transbronchial lung biopsy revealed bronchiolocentric alveolitis and well-formed non-necrotizing granulomas were present. She had used a jet bath before the onset of symptoms and mycobacterial culture revealed the presence of Mycobacterium avium complex (MAC) in sputum sample, BAL samples and jet bath water. Restriction fragment length polymorphism (RFLP) analysis revealed that the isolated MAC were essentially clonal. She had used the jet bath for the inhalation provocation study, and after the challenge she complained of dyspnea and have body temperature increased. We diagnosed hot tub lung due to Mycobacterium avium complex. Because avoidance of the jet bath caused improvement of her symptoms and reduced her fever and PaO2 increased by 10 Torr but did not improve the CT findings, antimycobacterial drugs were prescribed. The patient recovered fully. This case proves that the cause of hot tub lung is the use of jet bath through the inhalation provocation study.

[Long-term CT findings of X-linked agammaglobulinemia with bronchiectasis diagnosed in an adult].

We report a case of X-linked agammaglobulinemia who presented with bronchiectasis. The patient had suffered pneumonia about every five years since childhood until he presented to our hospital at age 34 years old. CT showed bronchiectasis predominantly in the right middle lobe, lingula, and lower lobes. Administration of antibiotics resulted in symptomatic relief. Episodes of recurrent pulmonary infection and bronchiectasis indicated congenital immunodeficiency disorder. Investigation of lymphocyte subsets and serum immunoglobulin values showed remarkable reduction of B cells, IgG 772 mg/dl, IgA 216 mg/dl, and IgM 29 mg/dl. Flow cytometric assessment combined with genetic analysis was performed, and the results showed decreased expression of monocyte Bruton's tyrosine kinase (BTK) and missense mutation of Btk gene. We diagnosed X-linked agammaglobulinemia. IgG remained above 600 mg/dl in this case, we have not administered immunoglobulin after discharge. He suffered from pneumonia in 2004 and 2006 and bronchiectasis has progressed. In this report, we present a case including CT findings over a period of 8 years.

Comparative analysis of gene expression between renal cortex and papilla in nedaplatin-induced nephrotoxicity in rats.

To elucidate the mechanism of nephrotoxicity caused by anti-neoplastic platinum complex, nedaplatin (NDP), treatment with a particular focus on the renal papillary toxicity, we analysed the gene expression profiles of two renal regions, the cortex (RC) and the papilla (RP) in rat kidneys. Male Wistar rats received a single administration of 10 mg/kg intravenous NDP or vehicle alone (5% xylitol solution) and were sacrificed six days later. The kidneys were dissected into the RC and RP and used for histopathological and microarray analyses. Histopathologically, NDP caused characteristic renal lesions, such as necrosis, single cell necrosis (with TUNEL TdT-mediated dUTP-biotin nick end labelling-positive) and regeneration/hyperplasia of the epithelial cells in both renal regions. Global gene expression analysis revealed that several genes involved in various functional categories were commonly deregulated in both renal regions, such as apoptosis, cell cycle regulation, DNA metabolism, cell migration/adhesion and cytoskeleton organization or genes induced as a perturbation of oxidative status and calcium homeostasis. Comparative analysis of gene expression between RC and RP revealed that genes encoding several subtypes of cytokeratins were identified as being specifically overexpressed in RP by the NDP treatment. Differential expression patterns of these selected genes observed by microarray analysis were further confirmed by quantitative real time RT-PCR and immunohistochemistry, which demonstrated increased expression of cytokeratins (CKs) 14 and 19 at the epithelium covering RP and/or collecting duct epithelium. Overall, the results contribute to understanding the renal molecular events of NDP-induced nephrotoxicity including novel potential biomarker genes encoding CKs 14 and 19 that may serve as indicators of renal papillary toxicity.

Pulmonary Schizophyllum commune infection developing mucoid impaction of the bronchi.

A 54-year-old woman was admitted for cough, sputum, and an abnormal chest X-ray shadow. Bronchoscopy showed mucoid impaction of the bronchi (MIB). Histopathologic evidence of mucous plugs was consistent with one component of allergic bronchopulmonary mycosis. Schizophyllum commune (S. commune) was identified. Two attempts at removal of the mucous plugs were unsuccessful. Itraconazole was then administered, and the mucous plugs disappeared. There are few reports of MIB due to S. commune; we herein report a case of MIB due to S. commune infection.

[A case of the metastatic calcification of trachea, bronchus, and lung].

A 43-year-old man with chronic renal failure who had been treated by continuous ambulatory peritoneal dialysis (CAPD) was admitted to our hospital because of dry cough. Blood gas analysis showed hypoxemia and metabolic alkalosis. Laboratory data showed elevated levels of phosphorus, BNP, and KL-6. Lung function tests showed restrictive ventilatory failure and impairment of diffusing capacity. Chest CT revealed centrilobular ground-glass opacification in both lung fields, irregular reticular abnormality in left lung field, and calcification around the left shoulder joint. Bronchoscopy revealed a white protruding lesion in the trachea and bronchial membranous portion. Calcified metastasis in the bronchus and lung was confirmed by transbronchial and lung biopsy. Because of no improvement by administration of sevelamer, he started with hemodialysis once a week in addition to CAPD. Cough and bilateral ground-glass opacity were improved.

Characterization of pancreatic islet cell tumors and renal tumors induced by a combined treatment of streptozotocin and nicotinamide in male SD rats.

We herein investigated the histopathological features, including proliferative activity and immunoexpression, of pancreatic islet cell tumors (ICTs) in male SD rats induced by streptozotocin (STZ) and nicotinamide (NA), and discussed their relevance to biological behaviors and prognoses. A total of 70 and 43% of rats developed ICTs 37-45 weeks after the treatment with STZ (50 or 75mg/kg, i.v.) and NA (350mg/kg, twice, p.o.), respectively. Among the islet tumors observed in the STZ/NA-treated groups, 75% were adenomas, while 25% were carcinomas. Most STZ/NA-induced carcinomas were characterized by well-differentiated tumor cells with/without local invasion into the surrounding tissues, and weak proliferative activity. No outcome such as distance metastasis and death was noted. All of the ICTs strongly expressed insulin, part of which had hormone productivity; however there were no hypoglycemia-related clinical signs such as convulsion in these rats 36 weeks after the treatment. These results suggested that rat ICTs induced STZ/NA have small impact on biological activity or prognosis. STZ/NA treatment significantly increased of focal proliferative lesions in the kidney, liver and adrenal glands other than pancreatic islets. Of the STZ/NA-induced kidney tumors, more than 60% were renal cell adenomas, and many of them were basophilic type. The incidence of eosinophilic or clear cell type of tumors was less than 10%, respectively. Immunohistochemical analyses revealed that many of the STZ/NA-induced basophilic type of renal tumors were derived from proximal tubules, whereas the clear cell and eosinophilic types were derived from collecting tubules.