Hiroshi Ohnishi

Circulating KL-6 levels in patients with drug induced pneumonitis

Background: The circulating level of KL-6/MUC1 is a sensitive marker for various interstitial lung diseases. Previous case reports have suggested that KL-6 may also be increased in some patients with drug induced pneumonitis. A study was undertaken to determine whether serum KL-6 could be a marker for particular types of drug induced pneumonitis. Methods: The findings of high resolution computed tomographic (HRCT) chest scans of 30 patients with drug induced pneumonitis were reviewed separately by two independent observers. The pneumonitis was classified into four predominant patterns: widespread bilateral consolidation (diffuse alveolar damage, DAD; n=7), fibrosis with or without consolidation (chronic interstitial pneumonia, CIP; n=11), consolidation without fibrosis (bronchiolitis obliterans organising pneumonia or eosinophilic pneumonia, BOOP/EP; n=8), and diffuse ground glass opacities without fibrosis (hypersensitivity pneumonitis, HP; n=4). Serum KL-6 levels were measured by a sandwich enzyme linked immunosorbent assay. Results: The overall sensitivity of serum KL-6 in detecting drug induced lung disease was 53.3%, which was lower than its sensitivity in detecting other interstitial lung diseases. However, the KL-6 level was increased in most patients with a DAD or CIP pattern (16/18; 88.9%) and was closely correlated with their clinical course. In contrast, serum KL-6 levels were within the normal range in all patients with a BOOP/EP or HP pattern. Conclusions: Particular patterns detected by HRCT scanning, such as DAD and CIP but not the BOOP/EP or HP patterns, are associated with increased circulating KL-6 levels in drug induced pneumonitis. Serum KL-6 levels may reflect the clinical activity of the particular disorders.

Successful Treatment of Obstructive Sleep Apnea Syndrome Improves Autonomic Nervous System Dysfunction

Autonomic nervous system (ANS) dysfunction may be implicated in the subsequent development of cardiovascular disease in patients with obstructive sleep apnea syndrome (OSAS). To confirm the relation between OSAS and ANS dysfunction, we prospectively investigated ANS function in 7 patients with moderate or severe OSAS; 7 healthy age-matched volunteers were for control. We also studied ANS function before and after treatment in the patients with OSAS to evaluate the effect of OSAS treatment on ANS dysfunction. The body mass index of patients with OSAS was 32.2 (27.4–45) (median [range]) kg/m2. The patients were treated by nasal continuous positive airway pressure (n = 5) or uvulopalatopharyngoplasty (n = 2). The apnea/hypopnea index decreased markedly from 42.1 (30.6–77.2) events/hr of sleep before treatment to 2.3 (1.4–3.8) after treatment. To evaluate ANS function, the coefficient of variation of the RR interval (CV-RR) and corrected QT (QTc) interval on the electrocardiogram at rest and the heart rate (HR) responses to blood pressure (BP) changes during the Valsalva maneuver were studied. Baseline HR of OSAS patients was significantly higher than that of the control subjects (p < .05). The Valsalva ratio (VR), baroreflex sensitivity (BRS), and CV-RR values in patients with OSAS were significantly lower than those of the control subjects (all, p < .005). However, there were no significant differences in systolic and diastolic BP or QTc intervals. After treatment, VR, BRS, and CV-RR values increased significantly compared with those before treatment in patients with OSAS (all, p < .05). There were no significant differences in systolic and diastolic BP, HR, or QTc intervals measured before and after treatment. These results suggest that impaired ANS function is present in patients with OSAS and can be improved by successful treatment of OSAS.

Metastatic renal cell carcinoma presenting as multiple pleural tumours

Abstract:  A 66‐year‐old man was admitted with dyspnoea. Chest X‐ray and chest computed tomography (CT) demonstrated a left‐sided pleural effusion and multiple tumours, suggesting malignant mesothelioma in the left pleural space, but there were no pulmonary lesions. However, abdominal CT revealed a right renal tumour. An ultrasonography‐guided needle biopsy of the pleural mass provided evidence of metastatic renal cell carcinoma (RCC). The pleural lesions dramatically decreased in size following right radical nephrectomy and subsequent interferon‐α treatment. While the thorax is a frequently affected site of RCC, sole pleural metastases are rare and are often secondary to lung involvement. Batsons plexus, a network of vertebral valve‐less veins with multiple connections, is likely responsible for the contralateral pleural metastases of RCC.

Purification of the murine heat-stable antigen from erythrocytes

The rat anti-mouse erythrocyte (MRBC) monoclonal antibody (mAb), R13, has been developed. The MRBC membrane protein recognized by R13 (R13-Ag) can be purified by loading the butanol-extracted MRBC membrane solution on a R13-conjugated Cellulofine column in the presence of 0.1% CHAPS followed by elution with 1% CHAPS. The amino acid sequence of the affinity-purified R13-Ag corresponded to that predicted from the cDNA for the murine heat-stable antigen. It was revealed that the actual heat-stable antigen was composed of 27 amino acids.

Isolation of mouse complement component C7

Mouse complement component C7 was purified from serum by a sequential procedure of fractionation precipitation by ammonium sulfate, followed by DE-52 anion exchange chromatography. Protein G affinity column chromatography, Mono S cation exchange chromatography and Superdex 200 gel filtration. The final product contained a highly purified mouse C7 component showing a single band on SDS-PAGE at the apparent Mrs of 90 kDa and 100 kDa under non-reduced and reduced conditions respectively. The yield of C7, which was measured by the biological activity, was 7.0%