Sinobronchial allergic mycosis syndrome in an elderly male.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) and allergic fungal rhinosinusitis (AFRS) are characterized by hyper-responsiveness of the respiratory tract and the nasal cavity and paranasal sinuses, respectively to Aspergillus species and AFRS causes chronic rhinosinusitis. Herein, we report the first case of sinobronchial allergic mycosis (SAM) syndrome, defined as ABPA with concomitant AFRS, caused by Aspergillus fumigatus patient > 80 years. CASE PRESENTATION: An 82-year-old male with interstitial pneumonia who returned for follow-up exhibited high-attenuation mucus plug in the right intermediate bronchial trunk, infiltration in the right lung field, and right pleural effusion on regular chest computed tomography (CT). We found unilateral central bronchiectasis in the right upper lobe. Similarly, CT scan of the paranasal sinuses revealed high-attenuation mucus plugs in left ethmoid sinuses. Biopsy specimens from the plugs in the right intermediate bronchial trunk and the left ethmoid sinuses revealed allergic mucin with layers of mucus eosinophils, eosinophil-predominant mixed inflammatory cell infiltrate and Aspergillus hyphae. The patient fulfilled all the major criteria for ABPA and AFRS, and was diagnosed with SAM syndrome. CT scan of the lung and paranasal sinuses revealed apparent amelioration after oral steroid therapy. CONCLUSION: Despite mostly reported in relatively young patients, SAM syndrome can occur in elderly individuals as well.

Surgical resection for clinical stage I high-grade neuroendocrine carcinoma of the lung.

BACKGROUND: There are few reports about the factor influencing the prognosis of high-grade neuroendocrine carcinoma. In this study, we evaluated surgical outcome of clinical stage I high-grade neuroendocrine carcinoma. METHODS: Patients who underwent curative surgery for high-grade neuroendocrine tumors of the lung in clinical stage I were included in this study. We retrospectively analyzed 27 consecutive patients. The aim of this study was to clarify the clinical course of the disease after surgery and what factors influence the prognosis. RESULTS: Twenty-two patients have small cell carcinoma, and 5 patients have large cell neuroendocrine carcinoma. Patients who could undergo surgery within 60 days after the first visit (p < 0.01) and undergo lobectomy (p < 0.01) and whose pro-gastrin-releasing peptide ≦ 72 pg/ml (p = 0.04) performed good prognosis after surgery. In multivariate analysis, surgery within 60 days and operative procedure were independent factors associated with OS. CONCLUSION: Surgical resection for clinical stage I high-grade neuroendocrine carcinoma of the lung should be performed as early as possible, and better outcome can be obtained with lobectomy than partial resection.

Nucleotide excision repair-dependent DNA double-strand break formation and ATM signaling activation in mammalian quiescent cells.

Histone H2A variant H2AX is phosphorylated at Ser(139) in response to DNA double-strand break (DSB) and single-stranded DNA (ssDNA) formation. UV light dominantly induces pyrimidine photodimers, which are removed from the mammalian genome by nucleotide excision repair (NER). We previously reported that in quiescent G0 phase cells, UV induces ATR-mediated H2AX phosphorylation plausibly caused by persistent ssDNA gap intermediates during NER. In this study, we have found that DSB is also generated following UV irradiation in an NER-dependent manner and contributes to an earlier fraction of UV-induced H2AX phosphorylation. The NER-dependent DSB formation activates ATM kinase and triggers the accumulation of its downstream factors, MRE11, NBS1, and MDC1, at UV-damaged sites. Importantly, ATM-deficient cells exhibited enhanced UV sensitivity under quiescent conditions compared with asynchronously growing conditions. Finally, we show that the NER-dependent H2AX phosphorylation is also observed in murine peripheral T lymphocytes, typical nonproliferating quiescent cells in vivo. These results suggest that in vivo quiescent cells may suffer from NER-mediated secondary DNA damage including ssDNA and DSB.

Regulation of adenosine 5'-triphosphate (ATP)-gated P2X(4) receptors on tracheal smooth muscle cells.

We examined the effects of extracellular adenosine 5'-triphosphate (ATP) on single airway smooth muscle (ASM) cells from porcine trachea using a patch-clamp technique. ATP induced a sustained inward current. Phospholipase C inhibitor U-73122 failed to inhibit the current, suggesting the involvement of P2X receptor. A specific effecter of P2X(4), ivermectin, augmented the current indicating the existence of P2X(4) receptors. Immunohistochemistry and reverse transcription/polymerase chain reaction analysis and Western blot analysis also showed the distribution of the P2X(4) receptors. The inward current was reduced by SKF-96365, an inhibitor of both voltage-dependent Ca(2+) channels (VDCCs) and voltage-independent Ca(2+) channels, although a VDCC antagonist, verapamil, did not affect the current. SKF-96365 caused complete suppression of both the increase in the intracellular Ca(2+) concentration and the contraction of ASM cells induced by ATP. Our results demonstrate that P2X(4) receptors exist on ASM and that the receptors are responsible for Ca(2+) influx. These findings suggest that the Ca(2+) influx regulated by P2X(4) receptors plays an important role in ASM contraction by a pathway distinct from VDCC.

A potentiating effect of endogenous NO in the physiologic secretion from airway submucosal glands.

It is known that several second messengers, such as Ca(2+) or cAMP, play important roles in the intracellular pathway of electrolyte secretion in tracheal submucosal gland. However, the participation of cGMP, and therefore nitric oxide (NO), is not well understood. To investigate the physiologic role of NO, we first examined whether tracheal glands can synthesize NO in response to acetylcholine (ACh), and then whether endogenous NO has some effects on the ACh-triggered ionic currents. From the experiments using the NO-specific fluorescent indicator 4,5-diaminofluorescein diacetate salt (DAF-2DA), we found that a physiologically relevant low dose of ACh (100 nM) stimulated the endogenous NO synthesis, and it was almost completely suppressed in the presence of the nonspecific NO synthase (NOS) inhibitor Nomega-Nitro-L-arginine Methyl Ester Hydrochloride (L-NAME) or the neuronal NOS (nNOS)-specific inhibitor 7-Nitroindazole (7-NI). Patch-clamp experiments revealed that both the NOS inhibitors (L-NAME or 7-NI) and cGK inhibitors (KT-5823 or Rp-8-Br-cGMP) partially decreased ionic currents induced by 30 nM of ACh, but not in the case of 300 nM of ACh. Our results indicate that NO can be synthesized through the activation of nNOS endogenously and has potentiating effects on the gland secretion, under a physiologically relevant ACh stimulation. When cells were stimulated by an inadequately potent dose of ACh, which caused an excess elevation in [Ca(2+)](i), the cells were desensitized. Therefore, due to NO, gland cells become more sensitive to calcium signaling and are able to maintain electrolyte secretion without desensitization.

Serum antibody against granulocyte/macrophage colony-stimulating factor and KL-6 in idiopathic pulmonary alveolar proteinosis.

Here we describe a case of idiopathic pulmonary alveolar proteinosis (I-PAP), in which anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) antibody and high level of KL-6 were found in the serum. Anti-GM-CSF antibody is responsible for I-PAP, and KL-6 is a serum marker for the activity of diffuse interstitial lung disease. A 38-year-old woman, who had no symptoms, was found to have an abnormal shadow on chest radiograph 5 years previously at a health check up. Chest radiograph showed a patchy shadow in the left lower lung field. Thoracoscopic biopsy was performed because the shadow had gradually expanded during the 5 years. Histological examination revealed proteinous material filling the alveoli and positive staining by the PAS method, suggesting PAP. Anti-GM-CSF antibody and a high level of KL-6 were detected in the serum at the time of diagnosis. Three years later, the shadow disappeared spontaneously. During this period, the level of KL-6 dramatically decreased, although that of GM-CSF antibody remained unchanged. The present case suggests that the serum level of the anti-GM-CSF antibody represents a useful marker for the diagnosis but not for follow-up of the clinical course. On the contrary, KL-6 is an excellent marker for the assessment of the clinical course of I-PAP.

Long-term use of corticosteroid eye drops delays the spontaneous remission of pulmonary sarcoidosis.

Topical corticosteroid eye drops are commonly used for ocular sarcoidosis. That systemic absorption of corticosteroids by eye drops may influence the clinical course of sarcoidosis may be speculated because it has been reported that the serum concentration of corticosteroids after drop administration was dose-related. To evaluate the effects of corticosteroid eye drops on the clinical course of patients with stage I pulmonary sarcoidosis, we compared the serum levels of angiotensin converting enzyme (ACE) and bilateral hilar lymphadenopathy (BHL) on chest radiographs of group CS, which is consisted of patients who received topical therapy of betamethasone in the form of eye drops for anterior uveitis, and group CN, which is consisted of patients who did not receive any medications throughout the entire course of the disease. Although the serum ACE level was not significantly different between groups CS and CN at the time of the diagnosis of pulmonary sarcoidosis, the level of serum ACE in group CS was significantly higher than that in group CN 20 months after the topical corticosteroid treatment (24 IU/ml and 16 IU/ml, respectively). Further, the size of BHL on chest radiography in group CS was significantly larger than that in group CN 20 months after the topical treatment (82% and 37% of before control, respectively). These findings suggest the possibility that the topical corticosteroid therapy influenced the clinical course of pulmonary sarcoidosis, inducing some delay in the spontaneous remission in the longterm course.