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Hepatocyte growth factor (HGF) is a potent angiogenic factor. The efficacy and safety of intramuscular injection of a naked plasmid encoding human HGF gene (beperminogene perplasmid, Collategene) was investigated in patients with critical limb ischemia (CLI) in a multicenter, randomized, double-blind, placebo-controlled trial. The randomization ratio for plasmid to placebo was 2:1. Injection sites were selected in each patient limb based on angiographic findings. Placebo or plasmid was injected on days 0 and 28. Evaluation of efficacy was carried out after 12 weeks. The primary end point was the improvement of rest pain in patients without ulcers (Rutherford 4) or the reduction of ulcer size in patients with ulcer(s) (Rutherford 5). Secondary end points were ankle-brachial pressure index, amputation, and quality of life (QOL). Forty-four patients were treated, and we performed interim analysis of efficacy in 40 patients. The overall improvement rate of the primary end point was 70.4% (19/27) in HGF group and 30.8% (4/13) in placebo group, showing a significant difference (P=0.014). In Rutherford 5 patients, HGF achieved a significantly higher improvement rate (100% [11/11]) than placebo (40% [2/5]; P=0.018). HGF plasmid also improved QOL. There were no major safety problems. HGF gene therapy is safe and effective for CLI. [ABSTRACT FROM AUTHOR]

Dual-targeted therapy for antiangiogenesis and antilymphangiogenesis represents a potentially effective strategy for the treatment of various malignancies. Therefore, the goal of the present study was to identify genes that encode inhibitors of both angiogenesis and lymphangiogenesis. Using a cDNA library obtained from Lewis lung carcinoma (LL/2), a candidate gene was identified by the evaluation of growth inhibition in aortic and lymphatic endothelial cells (EC) as that coding for the mouse cold shock domain protein A (mCSDA). Overexpression of mCSDA significantly repressed cell proliferation and c-fos promoter activity in aortic, venous and lymphatic ECs. CSDA is a DNA-binding protein that binds to the hypoxia response element (HRE). Furthermore, of importance, we revealed that CSDA could directly bind to the serum response element (SRE) sequence, resulting in the inhibition of SRE activity, which may lead to growth inhibition in ECs. In an LL/2-inoculated mouse model, tumor growth was significantly repressed in an mCSDA-injected group. Histopathological analysis revealed that expression of blood and lymphatic EC markers was significantly decreased in mCSDA-injected groups. In conclusion, these data suggest that expression of CSDA can repress angiogenesis and lymphangiogenesis via direct binding to SRE in addition to HRE.Oncogene (2008) 27, 1821–1833; doi:10.1038/sj.onc.1210824; published online 15 October 2007 [ABSTRACT FROM AUTHOR]

: Our objective was to investigate the clinical significance of Th1 and Th2-type cytokines, such as interferon-γ (IFNγ) interleukin (IL)-12, IL-4 and IL-10, in the mononuclear cells (MNC) of the synovial fluid (SF) in patients with rheumatoid arthritis (RA). The cytokine production in the MNC obtained from the SF (SF-MNC) in 30 patients with RA and 10 with gout was examined by measuring the mRNA levels of IFNγ, IL-12, IL-4 and IL-10 by semiquantitative RT-PCR. The mRNA levels of IFNγ, IL-4 and IL-10 were significantly higher in the SF-MNC of RA patients than in those of gout patients (p<0.001, p<0.01 and p<0.001, respectively). Correlations between mRNA levels were significant for IL-12 and IL-4, IL-12 and IL-10, and IL-4 and IL-10 (p<0.05). The mRNA levels of IL-4 and IL-10 were very low compared to those of IL-12 in seven of the 30 patients with RA; all of these patients were in stage 4, and serum levels of CRP, ESR and blood platelet count, which are considered as indices of the severity of inflammation, were significantly elevated in these seven patients compared to the other 23 RA patients. The markedly reduced synthesis of both IL-4 and IL-10 mRNA could be considered to be related to the progression and/or activity of RA. The results of this study therefore indicate an imbalance in the levels of Th1 and Th2 cytokines at the site of inflammation in RA, and draw attention to the possibility of treatment of progressive or intractable RA with IL-4 and/or IL-10. [ABSTRACT FROM AUTHOR]

Abstract. The significance of serotonin in the pathogenesis of monocrotaline-induced pulmonary hypertension (MCT-PH) in rats, plasma serotonin concentrations, and the effect of a serotonin receptor antagonist administration in association with the number of proliferative cells were investigated. The thickness of the media of the small pulmonary arteries and the weight ratio of the RV to that of LV + S (RV/[LV + S] weight ratio) were used as indices of the severity of PH. Plasma serotonin concentrations were measured by high-performance liquid chromatography. Histopathologic analysis of the lung tissue was performed by hematoxylineosin and elastin van Gieson staining. Immunohistopathologic staining for proliferating cell nuclear antigen (PCNA) was performed to identify proliferative cells. The severity of PH as determined by the medial thickness of the small pulmonary arteries and RV/(LV + S) weight ratio in rats with MCT-PH was significantly reduced after treatment with MCI-9042 (p < 0.01 and p < 0.05, respectively). The serotonin concentration was significantly greater in MCT-PH rats than in normal control rats (p < 0.05). The scores for histopathologic changes, such as thickening of the alveolar walls and interstitial inflammatory cell infiltration in MCT-PH rats, were significantly reduced after treatment with MCI-9042 (p < 0.05 and p < 0.01, respectively). The number of PCNA-positive cells was significantly greater in MCT-PH rats than in normal control rats (p < 0.0001) and was reduced alter treatment with MCI-9042 (p < 0.0001). Treatment with MCI-9042 significantly inhibited the development... [ABSTRACT FROM AUTHOR]

A case of neuro-Behcet's syndrome is presented with sequential positron emission tomography (PET) studies. Regional cerebral blood flow (rCBF) and oxygen consumption (rCMRO) were decreased in the brain lesion; however, on follow-up studies 3 months after steroid therapy rCBF and rCMRO had increased in the lesion, which demonstrated the reversibility of this disease. Such monitored improvement may accurately reflect the early stage of the disease and its response to steroid therapy. [ABSTRACT FROM AUTHOR]

An intramedullary spinal cord ependymoma was studied by positron emission tomography (PET) using (C-methyl)-L-methionine (C-Met). MRI showed a homogeneously enhancing tumour at C6-T2 with cysts at its rostral and caudal ends. Sagittal PET images demonstrated highC-Met uptake in the solid portion of the tumour, particularly ventrally at C7-T2, where viable tumour cells proliferated in association with abundant perforating vessels. Met-PET would appear useful for delineating the viable protion of intramedullary ependymomas. [ABSTRACT FROM AUTHOR]

Two cases of histologically proven primary cerebral malignant lymphoma were examined serially with positron emission tomography (PET) usingC-methyl- l-methionine (C Met). Lesions delineated byC Met accumulation extended beyond enhancing areas on either X-ray computed tomography (CT) or magnetic resonance imaging. High uptake ofC Met accurately showed biologically active and residual tumours, at a time when disappearance of a contrast-enhancing lesion on CT seemed to indicate involution. PET provides valuable information on the extent of tumour and assessment of radiotherapy in malignant lymphoma. [ABSTRACT FROM AUTHOR]

A method using piezoelectric ceramics was newly devised which permitted measurements of intramyocardial pressure. In open-chest dogs, a directional non-uniformity of the intramyocardial pressure was observed, which may be attributable to the variation in the myocardial fibre orientation. [ABSTRACT FROM AUTHOR]

Colloid osmotic pressure (COP) of blood from the great cardiac vein was continuously measured by the use of a membrane colloid osmometer during reactive hyperemia resulting from temporary occlusion of the anterior descending branch of left coronary artery. The COP increased sharply but transiently after the release, then it decreased below the initial level and gradually recovered. It was concluded that a measurable amount of water moved from the capillary blood into the myocardial tissue and then flowed back slowly into the capillary blood. [ABSTRACT FROM AUTHOR]