Efficacy of macrolides on gastric motility in extremely low birth weight infants.

BACKGROUND: The efficacy of macrolide treatment on gastrointestinal motility and acquirement of feeding tolerance in extremely low birth weight (ELBW) infants are controversial. This study aimed to evaluate clinical effects of parenterally administered erythromycin (EM) and clarithromycin (CAM) on gastrointestinal motility in ELBW infants. METHODS: ELBW infants treated in Tokyo Medical University Hospital were retrospectively studied. Several outcomes of ELBW infants treated with EM or CAM were compared with those recognized before initiation of the medication, as well as with those of patients with no macrolide treatment. The primary outcomes included average gastric residual volume that was evaluated 3 hours after enteral feeding. Secondary outcomes were the number of patients who developed feeding intolerance, stool frequency, and other adverse events, such as respiratory comorbidities and pyloric stenosis. RESULTS: Among a total of 53 infants, 20 and 13 were treated with EM and CAM, respectively, whereas 20 infants were not administered macrolides. The gastric residual volume was significantly decreased after initiation of medication compared with before medication in the EM group, whereas that of the untreated group showed no change. When the EM and CAM groups were combined, the gastric residual volume was also significantly decreased after treatment compared with before treatment. An increase in stool frequency and pyloric stenosis were not observed in the groups. CONCLUSION: EM might be effective for acquiring feeding tolerance in ELBW infants. A future prospective study with a larger population is required to determine the efficacy of CAM.

Role of Toll-like Receptor 4 Expressed by Fibroblasts in Allograft Fibrosis in Mouse Orthotopic Tracheal Transplantation.

Development of chronic lung allograft dysfunction involves various alloimmune-independent insults including those mediated by Toll-like receptor (TLR) signaling, which is known to activate alloimmune responses. We hypothesized that TLR signaling may also contribute to the activation of fibroblasts and promoting allograft airway fibrosis. Mouse orthotopic tracheal transplants were conducted between major histocompatibility complex (MHC)-mismatched Balb/c donor and wild-type C3H or C3H-derived TLR4 mutant recipients (nonfunctional TLR4). Immunohistochemistry on day 21 showed significantly smaller alpha-smooth muscle actin (α-SMA)-positive areas in TLR4 mutant recipients than wild-type recipients (P = .01). No difference was found for CD3+ T-cell infiltration. Proliferation of alloreactive T cells derived from the recipient spleen showed no difference between TLR4 mutant and wild-type recipients in a mixed lymphocyte reaction. The effect of TLR4 signaling was examined in primary pulmonary fibroblast cultures both with lipopolysaccharide (LPS) and transforming growth factor (TGF)-ß1. Stimulation with LPS significantly increased expression of α-SMA mRNA in wild-type fibroblasts cultured with TGF-ß1 compared with the control without LPS (P = .001). Taken together, these findings suggest disruption of TLR signaling leads to reduced activation of fibroblasts without affecting T-cell infiltration and proliferation in this model. TLR4-mediated activation of fibroblasts may be a potentially important mechanism of allograft remodeling.

Long-term investigation of phosphorus removal by iron electrocoagulation in small-scale wastewater treatment plants.

Small-scale wastewater treatment plants (SWTPs), called Johkasou, are widely used as decentralized and individual wastewater treatment systems in sparsely populated areas in Japan. Even in SWTPs, nutrients should be removed to control eutrophication. An iron electrolysis method is effective to remove phosphorus chemically in SWTPs. However, it is necessary to determine the precise conditions under which phosphorus can be effectively and stably removed in full scale SWTPs for a long period. Therefore, long-term phosphorus removal from SWTPs was investigated and optimum operational conditions for phosphorus removal by iron electrolysis were analyzed in this study. Efficient phosphorus removal can be achieved for a long time by adjusting the amount of iron against the actual population equivalent. The change of the recirculation ratio had no negative effect on overall phosphorus removal. Phosphorus release to the bulk phase was prevented by the accumulated iron, which was supplied by iron electrolysis, resulting in stable phosphorus removal. The effect of environmental load reduction due to phosphorus removal by iron electrolysis was greater than the cost of power consumption for iron electrolysis.

Improvement of phosphorus removal by calcium addition in the iron electrocoagulation process.

Small-scale wastewater treatment plants (SWTPs) are widely used as decentralized wastewater treatment systems in sparsely populated areas of Japan. Iron electrolysis, an electrocoagulation technology, is installed in these SWTPs for phosphorus removal. Phosphorus can be removed via the formation of an insoluble compound containing phosphate and iron, such as FePO4; however, it was necessary to determine the conditions under which phosphorus can be effectively and stably removed in actual SWTPs. According to previous studies using iron compounds, improved phosphorus removal was obtained by Ca addition. It is therefore thought that calcium addition may also be effective in improving the phosphorus removal during iron electrolysis in SWTPs. It is also important to determine the chemical state of iron to understand the phosphorus removal mechanism during iron electrolysis. In this study, laboratory-scale batch experiments with the iron electrolysis method were conducted to investigate the effect of phosphorus removal using treated wastewater from actual SWTPs without or with Ca addition. The results indicated that the addition of Ca improved the phosphorus removal performance. Furthermore, phosphorus removal was inhibited in the presence of high dissolved organic carbon (DOC). The X-ray absorption fine structure measurements of the produced particulates in the experiments showed no substantial change in the chemical state of iron without or with Ca addition. The statistical analyses revealed the range of improving or inhibiting effects on phosphorus removal due to the Ca and DOC. Thus, the results of this study provided useful information pertaining to the influence of coexisting substances on phosphorus removal and the chemical state of iron in the produced particulates.

De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability, autistic behaviors and epilepsy.

Eukaryotic elongation factor 1, alpha-2 (eEF1A2) protein is involved in protein synthesis, suppression of apoptosis, and regulation of actin function and cytoskeletal structure. EEF1A2 gene is highly expressed in the central nervous system and Eef1a2 knockout mice show the neuronal degeneration. Until now, only one missense mutation (c.208G > A, p.Gly70Ser) in EEF1A2 has been reported in two independent patients with neurological disease. In this report, we described two patients with de novo mutations (c.754G > C, p.Asp252His and c.364G > A, p.Glu122Lys) in EEF1A2 found by whole-exome sequencing. Common clinical features are shared by all four individuals: severe intellectual disability, autistic behavior, absent speech, neonatal hypotonia, epilepsy and progressive microcephaly. Furthermore, the two patients share the similar characteristic facial features including a depressed nasal bridge, tented upper lip, everted lower lip and downturned corners of the mouth. These data strongly indicate that a new recognizable disorder is caused by EEF1A2 mutations.

Epithelial to mesenchymal transition in murine tracheal allotransplantation: an immunohistochemical observation.

BACKGROUND: Aberrant epithelial repair is a crucial event in the airway remodeling that characterizes obliterative bronchiolitis (OB) in transplanted lungs. Recent data from experiments using epithelial cell lines and human airway tissues from lung transplant recipients suggest that epithelial to mesenchymal transition (EMT) plays an important role in OB. The aim of this study was to clarify whether EMT is involved in airway remodeling in an animal model. METHODS: We performed orthotopic tracheal transplantation from BALB/c to C57BL/6 mice with from BALC/c to BALB/c mouse grafts as controls. Five allogeneic and 3 syngeneic recipients were humanely killed at predetermined postoperative days 2-12 as well as 14 and 21. Histology was evaluated using hematoxylin-eosin (H&E) staining. We studied the expression of specific markers, including E-cadherin, an epithelial marker; α-smooth muscle actin (SMA), and S100A4, mesenchymal markers, and zinc finger E-box-binding homeobox 1 (ZEB1), an EMT-related transcription factor. RESULTS: Histologic assessment of serial H&E stains of allogeneic grafts showed remarkable pseudostratified respiratory epithelium with subepithelial inflammatory cell infiltration, as well as denuded and flattened epithelium and subepithelial fibrosis. The dynamic epithelial changes occurred earlier than the subepithelial fibrosis. Immunohistochemical evaluation indicated the emergence of α-SMA- positive epithelial cells that were most prominent on day 7. The expression of E-cadherin was attenuated in α-SMA-positive epithelial cells. S100A4 was also expressed in epithelial cells. A few days before the intraepithelial expression of α-SMA, ZEB1 emerged in the nuclei of epithelial cells. CONCLUSIONS: We observed expression of an EMT-related transcription factor and mesenchymal markers along with the attenuation of epithelial marker expression in epithelial cells, several days before prominent subepithelial fibrosis formation, results that suggest epithelial cells to play an important fibrosis role in airway remodeling during epithelial to mesenchymal transition.

Divergence of ovipositor length and egg shape in a brood parasitic bitterling fish through the use of different mussel hosts.

Bitterling fishes deposit their eggs on the gills of living mussels using a long ovipositor. We examined whether ovipositor length (OL) and egg shape correlated with differences in host mussel species in the family Unionidae among populations of the tabira bitterling (Acheilognathus tabira) in Japan. Bitterling populations that use mussels in the sub-family Anodontinae possessed longer ovipositors and more elongated eggs than those using mussels of Unioninae, as expected from the difference in host size between the sub-families (anodontine mussels are larger than unionine mussels). Based on a robust phylogeny of A. tabira populations, we demonstrated that the evolution of both OL and egg shape were correlated with host differences, but not with each other, suggesting that these traits have been selected for independently. Our study demonstrates how adaptive traits for brood parasitism may diverge with host shift due to different host availability and/or interspecific competition for hosts.

Erosion bleeding as a late complication of chest wall reconstruction with a Dacron mesh silicone prosthesis.

A 71-year-old man who had undergone chest wall resection and reconstruction with a Dacron mesh silicone prosthesis for chondrosarcoma 23 years previously presented with a chest wall hematoma. Since the hematoma was found to increase in size over time, we performed an operation to achieve hemostasis. Operative findings showed that the prosthesis had separated into three sheets.

Laparoscopy-assisted appendectomy through an umbilical port in children.

INTRODUCTION: We report surgical techniques for single-incision laparoscopy-assisted surgery (SILAS) in the treatment of pediatric acute appendicitis. METHODS: We performed SILAS in 15 cases of acute appendicitis between January and September of 2009. SILAS is a surgical method that involves making the incision at the umbilicus, inserting a wound retractor XS, suspending the abdominal wall with a hook, and appendectomy with the same procedures as conventional appendectomy. RESULTS: SILAS appendectomy was performed in all 15 cases with the exception of one case where one 3-mm port was added. Compared to open appendectomy, blood loss was significantly lower and postoperative hospitalization time was shorter, although there was no significant decrease in operative time, or postoperative fasting time. No postoperative complications, such as wound infection, intestinal obstruction, intra-abdominal abscess, or bleeding, were encountered. CONCLUSION: SILAS was safely performed and is superior to open appendectomy with regard to cosmetic outcome.

[Thymoma with synchronous pulmonary metastasis; report of a case].

We report a resected case of thymoma with a solitary pulmonary metastasis. A 63-year-old woman had pointed out a solitary nodule in right lung field on chest X-ray. Computed tomography (CT) scan showed an anterior mediastinal tumor and a solitary lung nodule in the right lower lobe. Extended thymectomy and partial resection of right lung was performed. Pathological diagnosis showed an invasive thymoma (type B3) and a pulmonary metastasis. Post operative radiotherapy was administered and she is doing well 19 months following the resection. Thymoma with a solitary synclonous pulmonary metastasis is rare and is classified into Masaoka stage IVb. Generally, thymoma cases with distant metastasis are not indication for operation. But, if radical resection is possible, operation is recommended for good prognosis.

Laparoscopic Heller myotomy with Dor fundoplication for achalasia: long-term outcomes and effect on chest pain.

The aim of the present study was to evaluate the long-term outcomes of laparoscopic Heller myotomy with Dor fundoplication (LHD) and its effect on chest pain. Between June 1995 and August 2009, a total of 35 patients with achalasia underwent an LHD. The symptom scores were calculated by combining the frequency and the severity. Pre- and postoperative evaluations included symptom score, radiology, manometry, and 24-hour pH manometry. Median total symptom score was significantly lower than the preoperative score (19 vs 4, P < 0.001) at a median follow-up of 94 months. Among the 35 patients, 18 (51%) had chest pain. The frequency of chest pain was similar for the pre- and postoperative scores, but the severity tended to be less. Median esophageal diameter (5.4 cm vs 3.5 cm, P < 0.001) and lower esophageal sphincter pressure (41 mmHg vs 8.9 mmHg, P < 0.001) were significantly reduced after surgery. Median age, duration of symptoms, esophageal diameter, and lower esophageal sphincter pressure were similar between patients with and without chest pain prior to surgery. No significant differences were observed between the two groups in terms of amplitude, duration, and frequency of contractions from the findings of postoperative 24-hour esophageal manometry. Chest pain resolved in three patients (17%) and improved in seven patients (39%) after surgery. LHD can durably relieve achalasic symptoms of both dysphagia and regurgitation, and it can be considered the surgical procedure of choice. However, achalasic chest pain does not always seem to be related with patient characteristics and manometric findings.

[Lung cancer operation in situs inversus totalis patient].

Situs inversus totalis represents a complete mirror image anatomy of the normal arrangement of the thoracic and abdominal viscera. This rare condition may pose possible surgical problems due to anatomical abnormality. There were few reports of surgical treatment for lung cancer patient with situs inversus totalis. In this case report, we describe a 74-year-old patient with situs inversus totalis and primary lung cancer who underwent successful left upper lobectomy and systemic lymph node dissection. For this rare condition, detail preoperative evaluation of mirror image anatomy with computed tomography and bronchofiber optic examination was thought to be a key to carry out safe operative procedure.

Control of membrane fouling in membrane bioreactor process by coagulant addition.

The control of membrane fouling is an essential issue in membrane bioreactor (MBR) process. It has been recognized that the most important factors that affect membrane fouling are presence of soluble microbial products (SMP) and extracellular polymeric substances (EPS) in a reactor. The objective of this study was to examine the effect of the coagulant addition on the membrane fouling in the MBR process. Accordingly, laboratory scale batch experiments and MBR experiments were conducted using coagulant. In batch experiments, effective SMP removal and control of EPS release were observed by coagulant addition. Fe coagulant was slightly more effective than Al coagulant in the addition of same mole amount. Therefore, Fe was used as coagulant in MBR experiments. In MBR experiments, Fe solutions of 0 mg/L, 2,260 mg/L and 4,520 mg/L were added into the tanks (Run1, Run2 and Run3, respectively) with the flow rate of 200 mL/d. COD removal efficiencies of 97% and phosphorus removal efficiencies of 92% were observed by Fe addition in the MBR experiment. Membrane fouling occurred more often in Run1 than in the other two Runs. Membrane was cleaned 18, 9 and 5 times in Run1, Run2 and Run3, respectively during 40 days runs. This suggested that the membrane fouling was reduced by the coagulant addition. The protein and carbohydrate concentrations of the SMP in the fraction of 1 microm-0.4 microm in Run2 and Run3 were significantly lower than that in Run1 and the particle size of the activated sludge was obviously increased in Run2 and Run3. These results suggested that the coagulant addition is effective to control the membrane fouling.

Zoledronate facilitates large-scale ex vivo expansion of functional gammadelta T cells from cancer patients for use in adoptive immunotherapy.

BACKGROUND: Human gammadelta T cells can be activated by phospho-antigens and aminobisphosphonates such as zoledronate. Because they can kill tumor cells in a major histocompatibility complex (MHC)-unrestricted manner, adoptive transfer of activated gammadelta T cells may represent a novel cancer immunotherapy. We tested whether gammadelta T cells from advanced cancer patients can be expanded by zoledronate. METHODS: Peripheral blood mononuclear cells from healthy donors and patients with advanced non-small cell lung cancer, bone metastatic breast or prostate cancer, or lung metastatic colorectal cancer, were stimulated with zoledronate (5 microM) and interleukin (IL)-2 (1000 IU/mL) for 14 days. The phenotype and function of the expanded gammadelta T-cell populations from healthy donors and cancer patients were compared. RESULTS: Gammadelta T cells from cancer patients and healthy donors responded to zoledronate equally well in terms of both phenotype and function. gammadelta T cells grew rapidly in vitro and expression of effector molecules, such as interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, perforin, granzyme B, FasL and TRAIL, increased over time. Cytotoxicity peaked on days 12-14, and proliferation continued up to 14 days, during which time>1x10(9) gammadelta T cells could be obtained from a starting sample of 45-70 mL peripheral blood. DISCUSSION: Using the agent zoledronate, already widely used in the clinic, we have established that efficient large-scale ex vivo expansion of gammadelta T cells from cancer patients is possible. These cells exert potent cytotoxicity and may be used for autologous cellular immunotherapy of cancer.

[Posterior mediastinal hemangioma successfully resected with cardiopulmonary bypass; report of a case].

Mediastinal hemangioma is a rare tumor. We report a case of a 62-year-old woman with a posterior mediastinal hemangioma. She had a history of right breast cancer and a follow-up chest radiography revealed a mass located in the left posterior mediastinum. The size was about 80 mm in diameter. The tumor surrounded the descending thoracic aorta and involved intercostal arteries. Complete excision could be achieved by decompressing the descending aorta with the aid of partial cardiopulmonary bypass and the aortic cross-clamp. Histologically, the tumor was diagnosed as a benign hemangioma. It was reported that hemangioma would reccur after subtotal excision. To employ cardiopulmonary bypass was a very effective approach for the purpose of complete excision in our case.

A second-generation profiling system for quantitative methylation analysis of multiple gene promoters: application to lung cancer.

Cancer-specific gene promoter methylation has been described in many types of cancers, and various semi-quantified results have shown their usefulness. Here, we show a more sensitive and specific second-generation system for profiling the DNA methylation status. This method is based on bisulfite reaction of DNA and real-time PCR using two TaqMan MGB probes labeled with different fluorescence, followed by clustering analysis. Primers were designed with CpG-less sequences, and TaqMan MGB probes were designed to contain three or four CpG sites and to be shorter than conventional TaqMan probes. We have added new criteria for primer and probe design for further specificity. We confirmed the reliability of this system and applied it to analysis of lung cancers. Using 10 promoters, 90 primary lung cancers were clustered into six groups consisting of cases having similar smoking status and pathological findings. EGFR mutation and p16 promoter DNA methylation were exclusive, as previously reported; however, DNA methylation in other genes was unrelated to EGFR mutation. This system was also useful to distinguish double primary lung cancers from a single cancer with intrapulmonary metastasis. As above, our system has widespread availability in clinical use and biological research.

[Pulmonary thromboembolism after lung resection in patients with schizophrenia; report of 2 cases].

We report 2 cases of pulmonary thromboembolism after lung resection in patients with schizophrenia. The first case is a 67-year-old woman. She underwent right lower lobectomy for primary lung cancer and suddenly felt dyspnea 2 days after the operation. She was diagnosed pulmonary thromboembolism by computed tomography (CT) and lung perfusion scintigram, and recoverd soon. The second case is a 42-year-old man. He underwent partial resection of the right lung for metastatic germ cell tumor. Six days after the operation, he fell into acute respiratory failure and died in spite of resuscitation. The autopsy showed that the cause of death was pulmonary thromboembolism. Because patients with schizophrenia have high-risk of pulmonary thromboembolism, extreme care must be exercised to avoid it.

Comparison of several methods for BAP measurement.

It has been more important for management of water quality to estimate the amount of bioavailable phosphorus (BAP) in suspended solids (SS) entering lakes and estuaries. AGP test or extraction by 0.1 mol l(-1) NaOH (C-BOD) is widely used. Recently, highly bioavailable phosphorus (HBAP) was introduced to indicate a more easily soluble and bioavailable fraction using successive extraction by 0.1 mol l(-1) HCl and 0.1 mol l(-1) NaOH. New biologically measured BAP (B-BAP) using bacterial respiration activity was introduced in this paper. B-BAP was estimated from oxygen uptake rate (OUR), which was measured by a respiratory meter for BOD measurement using a pressure sensor. B-BAP is useful for a rapid and direct measurement of phosphorus bioavailability. B-BAP, HBAP and C-BAP in river SS were measured and compared with each other. The percentages of HBAP and B-BAP to PP were large in the urban river, while the percentage of NaOH-P or C-BAP was large in the rivers flowing in agricultural areas. By comparison with phosphorus fractions in paddy soil and activated sludge it was suggested that SS in the rivers flowing in agricultural areas mainly consisted of clay, silt or sand, while the SS in the urban river consisted of a large percentage of organic particles as well. Phosphorus in SS was suggested to be more easily bioavailable in the urban river than the rivers in agricultural areas. The ratio of C-BAP/B-BAP was large in the rivers in agricultural areas and small in the urban river. As HBAP contents were almost similar to B-BAP contents in the river SS, HBAP can be a suitable index of phosphorus indicating easily and rapidly the bioavailable fraction in SS.

Effectiveness of flow stabilization in small-scale wastewater treatment facilities.

Household type Johkasous which have a flow stabilization function were surveyed on their performance. The water level, flow velocity and SS were measured after the maximum flow entering the anaerobic filter chamber with or without flow stabilization operation. In operation without the flow stabilization, the flow peak directly reached the biofiltration chamber and the flow rate kept at 1 cm/sec during 3-4 min in the connection baffle between the two anaerobic chambers. This suggested the possibility of sludge transfer from the first anaerobic chamber. Moreover the increase of SS in the second anaerobic chamber indicated sludge transfer from the second anaerobic chamber to the biofiltration chamber. In contrast, in operation with flow stabilization the relaxation of the water flow in the second anaerobic chamber and the biofilm chamber was verified. By the increase of the water level in the first anaerobic chamber, the flow stabilization performance was satisfactorily obtained. A model describing the change of the water level was developed and the calculated values and the measured value agreed well. The model will be useful in the design of the flow stabilization function.