Pulmonary Artery Diameter (PAD) and the Pulmonary Artery to Aorta Ratio (PAD/AAD) as Assessed by Non-contrast Cardiac CT: The Association with Left Ventricular (LV) Remodeling and the LV Function

Objective Dilatation of the pulmonary artery itself (PAD: pulmonary artery diameter) or in relation to the ascending aorta (PAD/AAD: pulmonary artery diameter to ascending aortic diameter ratio) has been reported to be associated with pulmonary hypertension and with a prognostic outcome of either heart failure or cardiovascular events. We herein aimed to assess the correlations between pulmonary hypertension-related parameters PAD (or PAD/AAD) and left ventricular (LV) remodeling and LV function. Methods This retrospective study included 193 patients (ages: 67±12 years) who underwent both coronary CT angiography (CCTA) and echocardiography. The PAD and the AAD were measured on a transaxial non-contrast CCTA image at the level of the pulmonary artery bifurcation. Left ventricular mass (LVM), relative wall thickness ratio (RWT), left ventricular ejection fraction (LVEF), left atrial volume (LAV), and early mitral inflow velocity to mitral annular early diastolic velocity ratio (E/e'') were evaluated by echocardiography. The relationships between PAD (or PAD/AAD) and echocardiography parameters were assessed, and adjusted for the demographic data and cardiovascular disease (CVD) risk factors by a multivariable linear regression analysis. Results PAD (mean±SD: 2.6±0.4 cm) was positively correlated with LVM (r=0.34, p＜0.001), LAV (r=0.41, p＜0.001), and E/e'' (r=0.29, p＜0.001). PAD/AAD (mean±SD: 0.76±0.12 cm) was positively correlated with LVM (r=0.12, p=0.09), LAV (r=0.24, p＜0.001), and E/e'' (r=0.15, p=0.04). These correlations remained significant after adjusting for demographic data and CVD risk factors. PAD (or PAD/AAD) did not correlate with LVEF or RWT (p＞0.05). Conclusion Greater PAD or PAD/AAD is significantly associated with LV remodeling and an impaired LV function.     

Superior efficacy of MMCP regimen compared with VMCP and MMPP regimens in the treatment of multiple myeloma

OBJECTIVE: A newly designed combination chemotherapy for multiple myeloma, MMCP [ranimustine (MCNU), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL)], was analyzed and compared with the results of our previous randomized trial of VMCP [vincristine, MPH, CPM and PSL] and MMPP [MCNU, MPH, procarbazine and PSL]. METHODS: MCNU (33.3 mg/m2, div) on day 1 and MPH (4 mg/m2, po), CPM (66.7 mg/m2, po) and PSL (30 mg/m2, po) from day 1 to 4, were administered. Each cycle was repeated every 3 weeks. PATIENTS OR MATERIALS: From January 1991 until August 1995, 104 patients with multiple myeloma diagnosed at 10 hospitals of Nagoya Cooperative Study Group were enrolled. RESULTS: Of the 87 evaluable patients, partial response rate for MMCP was 65.5% and was significantly higher than that of VMCP (13/47=27.7%, p<0.0001) and that of MMPP (21/47=44.7%, p=0.0196). A plateau attainment was observed in 49.4%. The percentage of the patients who attained plateau was significantly increased in the MMCP arm than in the VMCP arm (19.1 %, p=0.0017) but was not in comparison with that of MMPP arm (42.6%, p=0.6790). Patients treated with MMCP survived significantly longer than those treated with VMCP or MMPP (p=0.0009 by generalized Wilcoxon test, p=0.0023 by log-rank test) with median survival for MMCP being 31.6 months, for VMCP 22.5 months, and for MMPP 22.9 months. No significant differences were observed with respect to adverse effects among the three regimens. CONCLUSION: The newly designed MMCP is a candidate as an induction chemotherapy for multiple myeloma.     

Enigma homolog 1 scaffolds protein kinase D1 to regulate the activity of the cardiac L-type voltage-gated calcium channel

AIMS: In cardiomyocytes, protein kinase D1 (PKD1) plays a central role in the response to stress signals. From a yeast two-hybrid assay, we have identified Enigma Homolog 1 (ENH1) as a new binding partner of PKD1. Since in neurons, ENH1, associated with protein kinase Cepsilon, was shown to modulate the activity of N-type calcium channels, and the pore-forming subunit of the cardiac L-type voltage-gated calcium channel, alpha1C, possesses a potential phosphorylation site for PKD1, we studied here a possible role of ENH1 and PKD1 in the regulation of the cardiac L-type voltage-gated calcium channel. METHODS AND RESULTS: PKD1-interacting proteins were searched by yeast two-hybrid screening. In vivo protein interactions in cardiomyocytes isolated from heart ventricles of newborn rats were tested by co-immunoprecipitation. Small interfering RNA and a dominant negative mutant of PKD1 were delivered into cardiomyocytes by use of an adenovirus. Calcium currents were measured by the patch-clamp technique. Both ENH1 and PKD1 interact with alpha1C in cardiomyocytes. This interaction is increased upon stimulation. Silencing of ENH1 prevented the binding of PKD1 to alpha1C. Moreover, a dominant negative mutant of PKD1 or the silencing of ENH1 inhibited the alpha-adrenergic-induced increase of L-type calcium currents. CONCLUSION: We found a new binding partner, ENH1, and a new target, alpha1C, for PKD1 in neonatal rat cardiomyocytes. We propose a model where ENH1 scaffolds PKD1 to alpha1C in order to form a signalling complex that regulates the activity of cardiac L-type voltage-gated Ca(2+) channels.     

Pioglitazone reduces atherogenic outcomes in type 2 diabetic patients

AIM: The aim of this study was to evaluate the anti-atherogenic outcomes of pioglitazone, a thiazolidinedione derivative, in type 2 diabetic patients. METHODS: Eight patients with poor diabetic control were treated with 15 mg of pioglitazone for 4 months. Blood samples were collected monthly, and the levels of fasting plasma glucose (FPG), HbA1c, and lipids, such as triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol, were measured. Other parameters, including immunorecative insulin (IRI), remnant-like particle-cholesterol (RLP-C), adiponectin, plasminogen activator inhibitor type 1 (PAI-1), tumor necrosis factor (TNF)- alpha , leptin, brain natriuretic peptide (BNP), and high-sensitivity (hs)-C-reactive protein (CRP), were examined at the beginning and end of the study. In addition, clinically adverse side-effects were evaluated. RESULTS: Treatment with pioglitazone significantly decreased the levels of HbA1c, FPG, the homeostasis model assessment of insulin resistance (HOMA-IR) index, RLP-C, PAI-1, TNF- alpha , and hs-CRP, but not the level, IRI, lipids, or leptin. In contrast, adverse side-effects, including body weight gain, liver dysfunction and edema, were not observed during this study. CONCLUSION: These results strongly suggested that treatment with pioglitazone has a greater clinical benefit for the prevention of atherosclerosis, including coronary heart diseases, without any adverse side-effects.     

Extraosseous Benign Notochordal Cell Tumor Originating in the Lung: A Case Report

Benign notochordal cell tumors (BNCTs) are tumors originating in the axial skeleton, where chordomas occur. Although very rare, some cases of extraosseous chordoma, such as in the soft tissue and lungs, have been reported. We report a case of a primary tumor showing the notochordal characteristics of BNCTs within the axial skeleton.An asymptomatic 57-year-old woman presented with an abnormal shadow on her chest radiograph; chest computed tomography revealed a well-defined round nodule. The resected sample tissue contained a jelly-like small nodule. Histologically, it was identified as a BNCT, based on minimal nuclear atypia, extremely low mitotic activity within the tumor cells lying in a sheet-like arrangement, and focal immunopositivity for brachyury.This is the third case report of BNCT originating in the lungs; BNCTs are considered asymptomatic tumors that are identified by using highly developed chest imaging technology; however, our findings also suggest that these notochordal tumors may potentially originate from extraosseous sites that lack ideal precursor cells. Our case suggests that notochordal tumors can arise from organs that are unrelated to known notochordal development.     

Expiratory activity of the inspiratory muscles during cough.

To investigate the neural mechanism of the expiratory activity of the inspiratory muscles during a cough, EMG of the respiratory muscles were recorded in anesthetized and tracheostomized dogs. A laparoscope was used to minimize injury to the abdominal muscles for implantation of the electrodes into the costal diaphragm. During the expulsive phase of a cough, the diaphragm was active in 7 of 12 dogs and the external intercostal muscle was active in 3 of 6 dogs. During a cough, the expiratory activity of the diaphragm, after the termination of its inspiratory activity, started at 52.9 +/- 24.6 ms, and that of external intercostal muscle started at 51.1 +/- 20.5 ms. The expiratory activity of the internal intercostal muscle and of the transversus abdominis started at 34.3 +/- 13.0 and 27.8 +/- 15.2 ms, respectively. The onset of expiratory activity of the inspiratory muscles is significantly later than that of expiratory muscles. Continuous activity in the expiratory muscles evoked by airway occlusion, i.e., Hering-Breuer reflex, was suppressed during the inspiratory phase of a cough, but not suppressed during the expulsive phase even when the expiratory activity of the diaphragm was observed. We concluded that the expiratory activity of inspiratory muscles is controlled independently of both expiratory activity of the expiratory muscles and inspiratory activity of the inspiratory muscles.     

Possible role of vascular endothelial cells in immune responses in colonic mucosa examined immunocytochemically in subjects with and without ulcerative colitis

Phenotypic characteristics of vascular endothelial cells of the colonic mucosa in patients with ulcerative colitis and healthy controls were studied with immunoperoxidase staining by light and electron microscopy. The cells could be classified into two groups according to their phenotypes; one was positive for von Willebrand factor and the other had an antigen detected by a monoclonal antibody, OKM5. The endothelial cells positive for von Willebrand factor were usually in relatively large blood vessels, and OKM5-positive cells were mostly located in small capillaries along the glandular epithelium. OKM5-positive endothelial cells also expressed HLA-DR and interleukin-1 (IL-1). In patients with ulcerative colitis, OKM5-positive endothelial cells and spindle-shaped cells that might be precursors of endothelial cells were more numerous in the lamina propria than in the other subjects. Thus, OKM5-positive endothelial cells may be important as antigen-presenting cells and immunoregulatory cells in the intramucosal immune system. Furthermore, colonic epithelial cells in patients with ulcerative colitis synthesized HLA-DR and IL-1, and may have a close relation to immune responses, such as antigen processing and presentation to immunocompetent cells. It was suggested that these cells have a close relation to the pathogenesis of the impaired immune responses in situ in ulcerative colitis.     

Comparative studies of commercially available particle agglutination assay and enzyme-linked immunosorbent assay for screening of human T-cell leukemia virus type I antibodies in blood donors.

Human T-cell leukemia virus type I (HTLV-I) transmission during blood transfusion can be prevented by screening for and eliminating blood containing anti-HTLV-I antibodies. For this purpose, we evaluated two commercial test kits for HTLV-I antibodies, Serodia-ATLA (particle agglutination assay [PA]) and Eitest-ATL (enzyme-linked immunosorbent assay [ELISA]), by using serum samples from Japanese blood donors. Of 2,316 serum samples, 39 (1.7%), 34 (1.5%), and 28 (1.2%) were positive for the antibody by PA, ELISA, and immunofluorescence (IF), respectively. The coincidence rate for antibody-positive and antibody-negative results was 99.5% between PA and IF, whereas it was 99.6% between ELISA and IF. The serum samples which were positive by IF were also positive by PA, whereas 2 of 26 IF-positive samples were negative by ELISA. All the samples positive by both PA and ELISA were shown to be positive by IF unequivocally. The samples positive by only one of the two methods (PA or ELISA) were different. Eleven and eight serum samples that were negative by IF but positive by PA and ELISA, respectively, were further studied for HTLV-I antibody by radioimmunoprecipitation. Three of the former but none of the latter were found to be positive for antibody. Moreover, a PA-positive but IF-negative serum sample was shown to have significantly decreased PA titers after 2-mercaptoethanol treatment. The PA was further shown to detect not only IgG antibody but also IgM antibody to HTLV-I after separation of this serum sample by high-performance liquid chromatography.