Genomic organization and regulation of expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) gene

Lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a recently identified receptor for oxidized low-density lipoprotein, one of the major atherogenic substances. Although LOX-1 was reported to be expressed abundantly in endothelial cells, including atheromatous lesions, the regulation of LOX-1 gene has not yet been clarified. In the present study, we isolated the rat LOX-1 gene and investigated the regulation of gene expression. The rat LOX-1 gene was encoded by a single copy gene spanning over 19 kilobases and consisted of eight exons. Exon boundaries correlated well with the functional domain boundaries of the receptor protein. The promoter region contained putative TATA and CAAT boxes and multiple cis-elements such as NF-kappaB, AP-1 and AP-2 sites, and a shear stress response element. Northern blot analysis revealed that LOX-1 gene expression was up-regulated 9-fold by shear stress, 21-fold by lipopolysaccharide, and 4-fold by tumor necrosis factor-alpha, in cultured vascular endothelial cells. LOX-1 was also expressed in macrophages but not in vascular smooth muscle cells. These data provide important information for elucidating the molecular mechanisms of LOX-1 gene regulation and suggest a role for LOX-1 in the pathophysiology of atherosclerotic cardiovascular disease.     

Characterization of alkaline phosphatase genes expressed in seminoma by cDNA cloning

Two members of a placental alkaline phosphatase (PLAP) family, PLAP and PLAP-like or germ cell alkaline phosphatase, are aberrantly expressed in tumors of ecotropic origin. To characterize alkaline phosphatase induced in seminoma, alkaline phosphatase cDNA clones were isolated from a cDNA library constructed from seminoma cells and characterized by nucleotide sequence determination. Thus, isolated cDNA clones were classified into two types, germ cell alkaline phosphatase (PLAP-like) and liver/bone/kidney-type alkaline phosphatase (L/B/K AP). These results suggest that other than the PLAP family members, the expression of L/B/K AP is enhanced in seminoma and can serve as a tumor marker in seminoma.     

Operation for chronic pulmonary thromboembolism accompanied by thrombophilia in 8 patients

BACKGROUND: Medical therapy for chronic pulmonary thromboembolism is limited, and surgical treatment has become more frequent recently. We have performed pulmonary thromboendarterectomy on 8 patients with chronic pulmonary thromboembolism accompanied by thrombophilia. METHODS: The patients were 6 men and 2 women aged 21 to 56 years (mean, 35 years). Five patients had antiphospholipid syndrome, 2 had protein C deficiency, and 1 had congenital antithrombin III deficiency. The preoperative condition was New York Heart Association functional class III in 5 and class IV in 3. Hypoxemia, marked pulmonary hypertension (mean pulmonary artery pressure, 47+/-6.7 mm Hg), and low cardiac output were observed in all patients. After a median sternotomy, deep hypothermia was induced using a cardiopulmonary bypass, and pulmonary thromboendarterectomy in the bilateral pulmonary arteries was performed under intermittent circulatory arrest. RESULTS: There were no operative deaths. Long-term respiratory management was needed postoperatively by 3 patients. In the remaining 5 patients, no reperfusion injury was observed. The arterial blood oxygen concentration improved, and the mean pulmonary pressure decreased to 16+/-5.5 mm Hg. The cardiac output also increased, and New York Heart Association functional class improved to I in 4 and II in 4 patients. CONCLUSION: Pulmonary thromboendarterectomy under deep hypothermic intermittent circulatory arrest was effective for chronic pulmonary thromboembolism accompanied by thrombophilia for which medical treatment is of limited value.     

Stereospecific analysis of monounsaturated triacylglycerols in cocoa butter

The enantiomeric composition of the monounsaturated triacylglycerols (TG) from cocoa butter was estimated. The monounsaturated TG were separated into three fractions by reversed-phase high-performance liquid chromatography (HPLC), and each fraction was subjected to the stereospecific analysis with chiral-phase HPLC. The results indicated that the major TG consisted of equal amounts of 1-stearoyl-2-oleoyl-3-palmitoyl-sn-glycerol (SOP-sn-TG) and POS-sn-TG (47 mol%), 1,3-distearoyl-2-oleoyl-glycerol (SOS-TG) (33 mol%), and POP-TG (19 mol%). The contents of SOP-sn-TG and POS-sn-TG are 1.30 times that of the POP-TG content, and the SOS-TG content is 1.30² times that of the POP-TG content. The term “priority factor” is proposed for the ratio of the stearoyl group/palmitoyl group, 1:30 at thesn-1 andsn-3 or 1(3)-position. It shows a distinct specificity for particular fatty acids or their Coenzyme A esters in random esterification at each position of the glycerol moiety in the biosynthesis of cocoa butter TG.     

Surgery for aortic dissection associated with congenital bicuspid aortic valve

The Distribution Moment (DM) model has simulated experimental data on skeletal muscle, but it has not been used previously to study the mechanics of active contraction in cardiac muscle. In contrast to previous models of striated muscle contraction, all parameters have physical meaning and assumptions concerning biophysical events within the cell are consistent with available data. In order to simulate cardiac muscle deactivation using the DM model it was necessary to make the cross-bridge detachment rates large for large displacements from the neutral equilibrium position of a cross-bridge. To examine the effect of cooperativity on cardiac muscle contraction, we used the DM model's tight coupling scheme with binding of one or two calcium sites regulating contraction. As observed experimentally, our model predicted a reduction of isometric tension development following rapid shortening lengthening transients when contraction is regulated by either one or two calcium binding sites. The predicted deactivating effect increased if the transient was applied late in the twitch when contraction is regulated by two calcium binding sites, but not when it is regulated by one site. This is the first study in which deactivation has been simulated without making any provisions for length-dependent calcium trononin dissociation.     

Production of fibroblast proliferative cytokines from T lymphocytes stimulated by a B cell lymphoma line and their functional heterogeneity

Human mononuclear leukocytes (MNL) produced several factors with fibroblast proliferation activity (FPA) for HFL-1, a human lung fibroblast cell line, when MNL were cocultured with irradiated BALL-1, a B cell lymphoma line (BCLL), but not with other BCLL. The cellular source of BALL-1-induced FPA seemed to be CD4-positive T lymphocytes. On isoelectric electrophoresis, major activity of BALL-1-induced FPA was detected in the fractions around pH 4-5, and minor activity was present in the fractions around pH 6-7. Major BALL-1-induced FPA consisted of at least 4 different fibroblast proliferation factors (FPFs) according to their molecular weight; 320-600 kDa (P-I), 50-110 kDa (P-II), 22-38 kDa (P-III) and 4.6-11 kDa (P-IV). P-I had affinity to heparin though the rest had little or no affinity. FPA of P-I was suppressed by an antibody against acidic FGF, and FPA of P-III was suppressed by an antibody against IL-6. On the other hand, FPA of P-II and P-IV was suppressed by none of the antibodies against cytokines with FPA, such as FGF, IL-4, IL-6, IFN-gamma, TGF-beta and TNF-alpha. It was thus suggested that P-I was acidic FGF, that P-III was IL-6, and that P-II and P-IV were different cytokines from those described above. Furthermore, it was found that P-II and P-IV failed to exhibit proliferation activity for human umbilical vein endothelial cells (HUVEC).(ABSTRACT TRUNCATED AT 250 WORDS)     

Noise suppression effect in an avalanche multiplication photodiode operating in a charge accumulation mode

A pixel configuration available to solid-state imagers using an avalanche multiplication photodiode operated in a charge accumulation mode, with each pixel as a photo-element, is proposed and stable avalanche multiplication gains over several tens are demonstrated by using a test circuit composed of discrete elements, equivalent to the pixel configuration. Moreover, it is found that the self-quenching effects inherent to the APD operating in this mode suppress the reset or avalanche induced excess noises, predominant in readout process and in charge accumulation process, respectively. These results are advantageous for a solid-state imager since the use of the avalanche multiplication simultaneously satisfies the two requirements of high sensitivity and wide dynamic range.<>     

Intrapelvic malignant schwannoma resected transsacrally

Chlorzoxazone (Parafon forte) overdose is rarely reported despite widespread use of this drug. This report describes a case of two episodes of chlorzoxazone overdose and coma in the same patient. Intubation and mechanical ventilation were required on the first presentation. Following the second overdose, intubation was averted and drug effects were reversed by use of the benzodiazepine antagonist, flumazenil. Although chlorzoxazone is not classified as a benzodiazepine, it may interact with benzodiazepine receptors, thus making flumazenil potentially useful in overdose states.     

Reliability of AllnAs/lnGaAs/lnP HEMT with WSi ohmic contacts

We have investigated the degradation mechanism of Al_0.48In_0.52As/In_0.53Ga_0.47As/ InP high electron mobility transistors (HEMTs) using WSi ohmic electrodes. Cross-sectional transmission electron microscopy (TEM) observation and en-ergy dispersive x-ray (EDX) analysis reveal impurities diffusion of gate electrode (titanium: Ti) and fluorine (F) in the AlInAs layer after a high temperature (T_a = 170°C operating life test for 500 h. The decrease of drain current (I_ds) during life test shows linear dependence on square root of aging time. It suggests that the degradation is controlled by a diffusion mechanism. Hence, the estimated degradation mechanism of this device is related with decrease of carrier concentration in the epitaxial layer by these diffused impurities. On the other hand, TEM and EDX show no degradation of WSi/InGaAs interface after aging. Therefore, the WSi electrode for this type of HEMT demonstrates excellent high stability under the accelerated operating life test.     

Alterations in the enzyme activity and protein contents of protein disulfide isomerase in rat tissues during fasting and refeeding

Elevated level of cellular lipid peroxidation can increase the incidence of vascular disease. The mechanism by which ketosis causes accelerated cellular damage and vascular disease in diabetes is not known. This study was undertaken to test the hypothesis that elevated levels of ketone bodies increase lipid peroxidation in endothelial cells. Human umbilical venous endothelial cells (HUVEC) were cultured for 24 h at 37 degrees C with ketone bodies (acetoacetate, beta-hydroxybutyrate). Acetoacetate, but not beta-hydroxybutyrate, caused an increase in lipid peroxidation and growth inhibition in cultured HUVEC. To determine whether ketone bodies generate oxygen radicals, studies using cell-free buffered solution were performed. They showed a significant superoxide dismutase (SOD) inhibitable reduction of cytochrome C by acetoacetate, but not by beta-hydroxybutyrate, suggesting the generation of superoxide anion radicals by acetoacetate. Additional studies show that Fe2+ potentiates oxygen radical generation by acetoacetate. Thus, elevated levels of ketone body acetoacetate can generate oxygen radicals and cause lipid peroxidation in endothelial cells, providing a possible mechanism for the increased incidence of vascular disease in diabetes.