Met-RANTES ameliorates fibrous airway obliteration and decreases ERK expression in a murine model of bronchiolitis obliterans.

OBJECTIVES: Bronchiolitis obliterans (BO) is the main cause of late mortality among long-term survivors of lung transplantation. Chemokine-chemokine receptor (CCR) interaction and subsequent recruitment of infiltrating cells to the graft are early events in the development of chronic rejection of transplanted lungs. The present study investigated whether blockade of chemokine receptors CCR1 and CCR5 with Met-regulated-on-activation, normal T cells expressed and secreted (RANTES), an amino-terminal modified derivative of RANTES/CCL5, affects the development of BO in murine model and we sought to determine the expression of RANTES/CCL5 and their relationship with extracellular signal-regulated kinase (ERK). Materials and Methods: BALB/c mouse tracheas were heterotopically transplanted into C57Black6 recipients and treated for 21 days with either Met-RANTES at 20 microg/day or vehicle. Animals were killed at 21 days after transplantation for histologic examination of ERK expression. RESULTS: RANTES/CCL5 was highly expressed in allografts compare to isografts. Met-RANTES treatment ameliorated fibrous airway obliteration in a mouse model of BO and decreased ERK expression. CONCLUSION: Blockade of chemokine receptors by Met-RANTES ameliorated airway obliteration and decreased ERK expression. These findings suggest that chemokine receptors CCR1 and CCR5 play significant roles in the development of chronic rejection and ERK may be a new molecular target for chronic rejection.     

A surgical case of aortic regurgitation with Beh?et disease

A case of Beh?et disease associated with aortic valve regurgitation treated with aortic valve replacement is reported. The patient was treated successfully with special surgical techniques for prevention of post operative paravalvular leakage and occurrence of pseudo aneurysm because the patient was under long-term steroid therapy for Beh?et disease.     

Endoscopic observation of pathophysiology of ventricular diverticulum

Background Although there have been reports dealing with ventricular diverticulum (VD) analyzed by cisternography and computed tomography (CT), those focusing on magnetic resonance imaging (MRI) or neuroendoscopic findings are rare. Case report We present a case of noncommunicating hydrocephalus caused by aqueductal stenosis with cystic lesion located in supracerebellar region. Third ventriculostomy was performed on this case. The conventional CT and MRI were compatible with usual VD, but neuroendoscopic examination suggested otherwise. The endoscopic view inside of the cystic lesion demonstrated passing veins and no membrane. We diagnosed this cystic lesion as a unique subtype of advanced VD mimicking spontaneous ventriculostomy. Endoscopic observation of the cyst was very useful for accurate diagnosis and safe treatment.     

Identification and viability assessment of dermatophytes infecting nail based on quantitative PCR of dermatophyte actin (ACT) mRNA]

The diagnosis and choice of treatment for dermatophytoses are usually based on the result of microscopic observation of hyphal elements and culture. However, false negative cultures have sometimes been encountered and appropriate timing of discontinuation of treatment has not been formulated. In this study, we attempted the identification and viability assessment of dermatophytes based on the quantitative measurement of dermatophyte actin (ACT) mRNA. An internal fragment of the ACT, 725 to 762 bp, was isolated by PCR from the genomic DNA of dermatophytes and sequenced. ACT intron-based primers were dermatophyte species-specific and primer pairs crossing the intron were dermatophyte genus-specific. The LightCycler (LC) instrument, employing the two-step RT-PCR/fluorescent hybridization system, was used to quantify the actin mRNA (ACT) of dermatophytes. A 669 bp ACT cDNA fragment was used as a quantification standard. Several mg of samples were collected from skin scales or nail plates before and after the treatment using oral terbinafine. The results indicated that quantification of ACT mRNA correlated with the results of culture and KOH examination and that copy numbers of dermatophyte ACT mRNA per mg sample decreased with progression of the therapy. This method comprises a sensitive (1 fg), specific, rapid (< 4 h) and quantitative assessment of the viability and identification of dermatophytes in skin tissue.     

The local hyperthermochemotherapy for pleural carcinomatosis]

Local hyperthermochemotherapy was performed in 17 cases to control malignant effusion and intrathoracic disseminated lesions. Of these 15 patients, 11 cases primary lung cancer, 4 cases metastatic lung cancer had pleural carcinomatosis and 2 cases were malignant diffuse mesotheliomas. The procedure was radiofrequency hyperthermia (13.56 MHz) maintaining the peripleural temperature at 42-43 degrees C for 45-60 minutes, combined simultaneously with the intrathoracic administration of cisplatin (1-2 mg/m2, bolus) through a thoracic double lumen trocar tube. The treatment was repeated from 2 to 4 times at 7-day intervals. In 14 cases (87.5%) complete or partial response according to the criteria of the Japan Lung Cancer Society were obtained. There were 2 cases of no change and one case that was impossible to evaluate. In one lung cancer case, the disappearance of pleural disseminated lesions was confirmed by flexible thoracoscopy after the procedure. In 12 cases, there were abdominal complaints due to side effects of the hyperthermochemotherapy, such as vomiting and nausea, but these symptoms were milder than those caused by intravenous injection of anti-cancer agents, for example cisplatin, in conventional chemotherapy treatment. The median survival time and 2 years survival of the patients with the present procedure were 15 months and 41.7% respectively. Although distant metastases appeared in most cases, none had local recurrence and particularly noteworthy pleural effusion was well controlled. The above experience suggested that the local hyperthermochemotherapy is useful to control pleural effusion and can improve the quality of life of patients with pleural carcinomatosis.     

Neuropathology of familial tauopathy

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) is a hereditary progressive neurodegenerative disorder. FTDP‐17 was originally defined in Ann Arbor, Michigan, in 1996. Since then, more than 100 families with FTDP‐17 have been described throughout the world, including 18 families identified in Japan. Genetic studies have identified 40 different mutations in the microtubule‐associated protein tau (MAPT) gene. The clinical features of FTDP‐17 are characterized by behavioral, cognitive and motor disturbances that may occur in various combinations and degrees. Neuropathologic examination shows that various degrees of atrophy may be present in the frontal and temporal lobes, basal ganglia, amygdala and hippocampus. All the brains from patients with FTDP‐17 have also shown the presence of tau deposits in neurons and glial cells. Mutations in MAPT may result in the increased splicing of exon 10, leading to 4‐repeat tau depositions in both neurons and glial cells. MAPT mutations outside of exon 10 show 3‐ and 4‐repeat tau deposits, predominantly in neurons with less glial pathology. Neuronal pathology may resemble that of Alzheimer’s disease or Pick’s disease because of the presence of neurofibrillary tangles or Pick‐like bodies, whereas glial pathology may resemble that of progressive supranuclear palsy or corticobasal degeneration because of the presence of coiled bodies, tufted astrocytes or astrocytic plaques. Correlations between genetic mutations and the heterogeneity of clinical and neuropathologic features remain unclear.