Objective B-type natriuretic peptide (BNP) is a cardiac hormone. The results of previous in vitro studies suggest that neurohumoral factors, and not only hemodynamic factors, may cause BNP secretion. In this study, we examined the impact of serum C-reactive protein (CRP) levels on the relationship between echocardiographic parameters and plasma BNP levels in patients with cardiovascular diseases.
Methods and Patients The study population comprised 417 patients who visited our cardiovascular unit with a problem. Both blood sampling and echocardiography were performed within one month.
Results Multiple regression analysis showed that plasma BNP levels were negatively correlated with male gender, body mass index, and estimated glomerular filtration rate, and positively correlated with serum CRP levels and left ventricular end-systolic dimension (LVDs). The study population was divided into two groups based on the 75th percentile of the serum CRP levels. Single regression analysis showed that a regression line between LVDs and plasma BNP levels was steeper in the group of patients with CRP levels above the 75th percentile. Multiple regression analysis revealed that the interaction term (LVDs × CRP) was significant, which means LVDs had more impact on plasma BNP levels at higher CRP levels.
Conclusion Plasma BNP levels increased with respect to the severity of cardiac dysfunction and serum CRP levels, and should therefore be considered a collective or total marker for life-threatening conditions including systemic inflammation, and not simply as a marker of cardiac dysfunction in patients with cardiovascular diseases.

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Objective Orthostatic hypotension during a hemodialysis (HD) session affects not only the modality but daily quality of life for HD patients because many of them have combined dysfunction of both sympathetic and parasympathetic nervous systems. Although various non-invasive methods have been applied for the evaluation of autonomic function, no monitor has been devised for measuring the dysfunction during blood purification therapy.
Patients and Methods We evaluated the usefulness of laser-Doppler blood flowmeter (LDF) for measuring autonomic function of stable 34 regular HD patients and 24 healthy controls. The LDF device was applied for autonomic test by measuring periflux blood flow decreasing velocity (PDV) accompanied with Valsalva maneuver. We also evaluated the correlation between PDV and conventional tests for atherosclerosis.
Results The average PDV (3.79 ± 1.77) in HD population level was significantly lower than that of healthy controls (8.72 ± 6.00). We also found a significant correlation between PDV and conventional methods such as heart rate variability and ankle-brachial blood pressure index.
Conclusion Measurement of PDV by LDF is as useful as a conventional method for evaluating autonomic function in HD patients. The convenience of the device offers the benefit of daily and frequent measurement of autonomic dysfunction.

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Objective To investigate the role of α₃β₁ integrin and α/β-dystroglycan in protective effects of 1,25(OH)₂D₃ on podocytes in rats with adriamycin-induced nephropathy.
Methods Sprague-Dawley rats were randomly divided into three groups: control group (NC), nephropathy group (NE), and nephropathy+1,25(OH)₂D₃ group (ND). Rats in NE and ND group were injected intravenously with adriamycin (0.1 mg/10 g body weight) to induce nephropathy, and those in ND group were then subcutaneously treated with 1,25(OH)₂D₃ for 8 weeks. Urinary protein level, number of urine podocytes, foot process width and glomerulosclerotic index were determined. Nephrin and podocin mRNA and protein expressions were determined by RT-PCR and western blot, respectively. Podocyte density and expressions of α₃β₁ integrin and α/β-dystroglycan (DG) were analyzed by immunohistochemistry and western blot, respectively.
Results The increase in proteinuria, podocyturia and width of foot process in NE group were ameliorated after treatment with 1,25(OH)₂D₃ for 8 weeks. The glomerulosclerotic index was significantly decreased in ND group when compared with NE group. The podocyte density in ND group (10.3 ± 1.64 cells/glomerulus) was significantly higher than that in NE group (8.43 ± 1.75 cells/glomerulus) (p=0.008). 1,25(OH)₂D₃ treatment could significantly up-regulate the mRNA and protein expressions of nephrin and podocin, and the protein expressions of α₃β₁ integrin and α/β-DG.
Conclusion The expressions of nephrin, podocin, α₃β₁ integrin and α/β-DG were decreased in rats with nephropathy. However, 1,25(OH)₂D₃ treatment could significantly up-regulate the expressions of nephrin, podocin, α₃β₁ integrin and α/β-DG proteins which might suppress podocyte detachment and podocytopenia.

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Objective Comorbidities of chronic obstructive pulmonary disease (COPD) have been recognized as an important issue in COPD management. We have reported that patients with liver diseases show a higher prevalence of COPD, but the number of patients with liver diseases was small and the details of liver diseases were not clearly investigated. In this study, we investigated the prevalence of COPD in patients with liver diseases by recruiting a large number of patients, and also investigated was the effect of hepatitis virus infection on COPD prevalence.
Patients and Methods Six hundred sixty-six patients were recruited from 9 primary care clinics and three hospitals. All of these patients were aged 40 years or older with chronic diseases and had not been diagnosed as having respiratory diseases. A spirometry was performed without administration of an inhaled bronchodilator. Airflow limitation was defined as FEV₁/FVC <70%. Underlying diseases were diagnosed by doctors of the clinics or the hospitals.
Results Two hundred fifty-six patients had liver diseases, and 410 did not. Of 410 patients without liver diseases, 37 patients (9.0%) were diagnosed as COPD, and of 256 patients with liver diseases, 35 patients (13.8%) were COPD. When the prevalence was analyzed according to smoking, age and gender, liver diseases showed a significantly high odds ratio (2.10, 95%CI 1.23-3.57, p=0.006), but hepatitis virus infection showed a non-significant tendency toward a high odds ratio.
Conclusion The patients with liver diseases had a significantly high prevalence of COPD. The presence of liver disease might become a useful predictor for the early detection of COPD.

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Objective Mutations in the dysferlin gene cause limb-girdle muscular dystrophy (LGMD) 2B and Miyoshi myopathy (MM), which are collectively named dysferlinopathy. Dysferlinopathy is the most frequent type of LGMD in the Japanese population. Molecular genetic analysis is essential for the diagnosis of dysferlinopathy because of its variable immunohistochemical patterns of biopsied muscles, including patterns similar to normal controls. The analysis of the entire dysferlin gene however, is time-consuming and laborious; therefore a simple and rapid screening method to detect hot spot mutations in the dysferlin gene is essential for the diagnosis of dysferlinopathy.
Methods We previously showed that 4 mutations, c.937+1G>A, c.1566C>G, c.2997G>T and c.3373delG account for 50% of all the mutations identified in Japanese dysferlinopathy patients. We performed a one-tube multiplex PCR, followed by extension of primers for each mutation with a fluorescence-labeled dideoxynucleotide to screen the 4 hot spot mutations.
Results The multiplex primer-extension reaction was developed on samples of known mutations. The extension products were represented as 4 different peaks that corresponded to a mutated nucleotide on electropherogram. Using the developed screening method, we were able to detect mutations in these hot spots in 3 samples out of 8 clinically suspected LGMD2B/MM patients in only approximately 8 hours. These 3 cases were definitely diagnosed as LGMD2B/MM by exonic sequencing.
Conclusion We have developed a simple and rapid screening method which could facilitate the definitive diagnosis of dysferlinopathy, contributing to an understanding of the genotype-phenotype correlations for dysferlinopathy.

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A 58-year-old woman was admitted with refractory fever despite receiving broad-spectrum antibiotics. She had hypoxemia, severe anemia, elevated levels of serum lactic dehydrogenase and soluble interleukin-2 receptor, and a positive direct Coombs test, which suggested an underlying autoimmune hemolytic anemia (AIHA). Chest computed tomography (CT) showed no abnormal findings, but she had hypoxia, and her alveolar-arterial oxygen difference (A-aDO₂) was increased. A random transbronchial lung biopsy (TBLB) was performed, and pathological analysis showed massive proliferation of tumor cells in the lumina of the small vessels. Intravascular large B-cell lymphoma (IVLBCL) was diagnosed, and her general status improved after chemotherapy.

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A 78-year-old woman with multiple tumors in the liver and spleen was diagnosed with follicular dendritic cell (FDC) sarcoma based on the histological picture of splenectomized specimen and its expression of CD21 and CD 23. As a paraneoplastic immune disorder, Coombs' test was positive although hemolysis was not obvious. Since systemic chemotherapies were ineffective for residual liver tumors, transcatheter arterial chemoembolization (TACE) was performed with subsequent tumor reduction. Currently, the patient is alive 27 months after the diagnosis with residual hepatic tumors favorably controlled by repeated TACE. Our experience suggests that TACE is useful for the management of hepatic FDC sarcoma.

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