A new brain CT reference line: the lower eyelid to the inner occipital base line closely parallels the Talairach-Tournoux line.

BACKGROUND: There is no standardized brain computed tomography (CT) reference line that can be determined on both scout and reformatted sagittal CT images. Here, a tangential line from the anterior edge of the lower eyelid to the inner table of the occipital base (LEL/O line) appears nearly parallel to the Talairach-Tournoux (T/T) line, which shows a consistent intracranial anatomical relationship among subjects, and acts as a standard reference line for magnetic resonance (MR) imaging. PURPOSE: To quantitatively validate the LEL/O line as a new standard brain CT reference line. MATERIAL AND METHODS: We measured: angle 1 = the LEL/O line on scout images from the LEL/O line on parasagittal CT images (n=93); and angle 2 = the LEL/O line on scout images from the T/T line on high resolution midsagittal MR images (n=97). Angles in a clockwise direction were defined as positive and were expressed as mean±SD with the 95% confidence interval (CI) of the SD. Angle 2 was measured independently by two observers and intraclass correlation coefficients (ICCs) were calculated. RESULTS: Angle 1 was -0.4°±1.2° (95% CI of SD 1.1°-1.5°); angle 2 was -0.4°±2.0° (95% CI of SD, 1.8°-2.4°). The ICC in the angle 2 measurement was 0.780 (P<0.001), which indicated high inter-observer reliability. CONCLUSION: The LEL/O lines on scout and parasagittal CT images show practically the same gradient, and these LEL/O lines are almost parallel to the T/T line. Use of the LEL/O line either for direct scanning or reformation can minimize intra- and inter-subject variations on CT images and mismatch between CT and MR images.

Breeding of fragrant cyclamen by interspecific hybridization and ion-beam irradiation.

Conventional breeding of cyclamen has relied on crossings among Cyclamen persicum cultivars without consideration of the scent of the flowers. Cyclamen purpurascens is a wild species with the most fragrant flowers in the genus Cyclamen. Allodiploid (2n = 2x = 41, AB) and allotriploid (2n = 3x = 65, AAB) plants have been produced from crosses of diploid and autotetraploid cultivars of C. persicum (2n = 2x = 48, AA; 4x = 96, AAAA) × diploid wild C. purpurascens (2n = 2x = 34, BB) by embryo rescue, but are sterile. Fertile allotetraploid (2n = 4x = 82, AABB) plants have been produced by chromosome doubling of the sterile allodiploids in vitro. Autotetraploid C. purpurascens (2n = 4x = 68, BBBB) has been produced by chromosome doubling of diploid C. purpurascens, and other fertile allotetraploids (2n = 4x = 82, AABB) have been produced from crosses of autotetraploid cultivars of C. persicum × autotetraploid C. purpurascens by embryo rescue. Commercial cultivars of fragrant cyclamen have been bred by conventional crosses among the allotetraploids. Mutation breeding using ion-beam irradiation combined with plant tissue culture has resulted in fragrant cyclamens with novel flower colors and pigments. In contrast, allotriploids (AAB) have not been commercialized because of seed sterility and poor ornamental value. The flower colors are determined by anthocyanins and flavonol glycosides or chalcone glucoside, and the fragrances are determined by monoterpenes, sesquiterpenes, phenylpropanoids, or aliphatics. Techniques for the production of fragrant cyclamen and knowledge of flower pigments and volatiles will allow innovation in conventional cyclamen breeding.

Directable needle guide: efficacy for image-guided percutaneous interventions.

Diagnostic and therapeutic image-guided percutaneous interventions have become increasingly important in the clinical management of various conditions. Though precise needle placement via a safe route is essential for successful percutaneous interventions, it is often difficult in cases of deeply situated, small lesions. The present paper describes the efficacy of the directable needle guide (DNG), which allows manipulation of the direction of a fine needle within organs. The DNG was used in patients for needle biopsy of hepatic (n = 26) and splenic (n = 1) lesions and for percutaneous ethanol injection therapy for liver tumors (n = 33) under sonographic or computed tomography guidance. The DNG enabled the direction of a 21- or 22-gauge needle to be successfully changed during needle advancement in all cases, allowing adjustment of the location of the needle tip or needle access root to avoid vessels, the gallbladder, and the lungs. We conclude that DNG increases the safety and ease of percutaneous interventions.

Molecular characterization of an anthocyanin-related glutathione S-transferase gene in cyclamen.

Anthocyanins are a subclass of flavonoids and are a major contributor to flower colors ranging from red to blue and purple. Previous studies in model and ornamental plants indicate a member of the glutathione S-transferase (GST) gene family is involved in vacuolar accumulation of anthocyanins. In order to identify the anthocyanin-related GST in cyclamen, degenerate PCR was performed using total RNA from immature young petals. Four candidates of GSTs (CkmGST1 to CkmGST4) were isolated. Phylogenetic analysis indicated that CkmGST3 was closely related to PhAN9, an anthocyanin-related GST of petunia, and this clade was clustered with other known anthocyanin-related GSTs. Expression analysis at different developmental stages of petals revealed that CkmGST3 was strongly expressed in paler pigmented petals than in fully pigmented petals, in contrast to the constitutive expression of the other three candidates during petal development. This expression pattern of CkmGST3 was correlated with those of other anthocyanin biosynthetic genes such as CkmF3'5'H and CkmDFR2. Molecular complementation of Arabidopsis tt19, a knockout mutant of an anthocyanin-related GST gene, demonstrated that CkmGST3 could complement the anthocyanin-less phenotype of tt19. Transgenic plants that expressed the other three CkmGSTs did not show anthocyanin accumulation. These results indicate CkmGST3 functions in anthocyanin accumulation in cyclamen.

Use of a novel coaxial guide needle-wire (GNW) combination system for computed tomography guided radiofrequency tumor ablation.

We developed a novel coaxial system using a fine guide needle wire (GNW) to safely and easily place the radiofrequency needle under CT-guidance. The GNW consists of a fine needle (diameter, 21-gauge; length, 150 mm) and a wire (0.018 inch, 250 mm). An exclusive radiofrequency cannula (14-gauge; 160 mm) was also used. This system was used for the treatment of six hepatocellular carcinomas in six patients. All lesions were located deeper than 10 cm from the needle entry site. This system was useful in performing CT-guided RF ablation for deeply or precariously located liver lesions particularly in patients who are unable to hold their breath.

Isolation and characterization of the fragrant cyclamen O-methyltransferase involved in flower coloration.

Anthocyanin O-methyltransferase (OMT) is one of the key enzymes for anthocyanin modification and flower pigmentation. We previously bred a novel red-purple-flowered fragrant cyclamen (KMrp) from the purple-flowered fragrant cyclamen 'Kaori-no-mai' (KM) by ion-beam irradiation. Since the major anthocyanins in KMrp and KM petals were delphinidin 3,5-diglucoside and malvidin 3,5-diglucoside, respectively, inactivation of a methylation step in the anthocyanin biosynthetic pathway was indicated in KMrp. We isolated and compared OMT genes expressed in KM and KMrp petals. RT-PCR analysis revealed that CkmOMT2 was expressed in the petals of KM but not in KMrp. Three additional CkmOMTs with identical sequences were expressed in petals of both KM and KMrp. Genomic PCR analysis revealed that CkmOMT2 was not amplified from the KMrp genome, indicating that ion-beam irradiation caused a loss of the entire CkmOMT2 region in KMrp. In vitro enzyme assay demonstrated that CkmOMT2 catalyzes the 3' or 3',5' O-methylation of the B-ring of anthocyanin substrates. These results suggest that CkmOMT2 is functional for anthocyanin methylation, and defective expression of CkmOMT2 is responsible for changes in anthocyanin composition and flower coloration in KMrp.

Increased level of pericardial insulin-like growth factor-1 in patients with left ventricular dysfunction and advanced heart failure.

OBJECTIVES: To test the hypothesis that the cardiac insulin-like growth factor-1 (IGF-1) system is up-regulated in the failing heart, we measured the pericardial (cardiac) and plasma (circulating) IGF-1 levels in coronary artery disease patients. BACKGROUND: Local IGF-1 systems are regulated differently from the systemic IGF-1 system. The cardiac IGF-1 system is up-regulated by the increased left ventricular (LV) wall stress. However, it remains unknown how this system is affected in LV dysfunction and heart failure. METHODS: We measured the plasma and pericardial fluid levels of IGF-1 and brain natriuretic peptide (BNP) in 87 coronary artery disease patients undergoing cardiac surgery, and examined their relationships with LV function and heart failure severity. The expressions of IGF-1 and IGF-1 receptor proteins were examined in endomyocardial biopsies obtained from other patients with normal or impaired LV function. RESULTS: The pericardial IGF-1 and BNP levels were positively correlated with the plasma BNP level (both p < 0.001). The pericardial IGF-1 level was increased in heart failure patients, whereas the plasma IGF-1 level was rather decreased. The pericardial IGF-1 level was inversely correlated with the LV ejection fraction (p < 0.001), whereas the plasma IGF-1 level was not. Positive immunostaining for IGF-1 and IGF-1 receptor proteins was enhanced in myocardial biopsies from failing hearts compared with those from nonfailing hearts. CONCLUSIONS: The pericardial IGF-1 level was increased in patients with LV dysfunction and heart failure, whereas the plasma IGF-1 level was decreased. These results may indicate that up-regulation of the cardiac IGF-1 system serves as a compensatory mechanism for LV dysfunction.

Circulating level of gelatinase activity predicts ventricular remodeling in patients with acute myocardial infarction.

BACKGROUND: Matrix metalloproteinase (MMP) plays an important role in the development of ventricular remodeling in an animal model of acute myocardial infarction (AMI). We examined whether circulating MMP activity can predict left ventricular (LV) remodeling after AMI in humans. METHODS: We measured the circulating level of MMP-2 and MMP-9 activities (gelatinase activity) at 14 days after the onset of AMI by gelatin zymography in 52 consecutive patients (age 62+/-2). All patients underwent direct PTCA and stenting at an acute stage, and were treated subsequently with losartan or enalapril. Biplane left ventriculography was performed at admission, and 2 weeks and 6 months after the onset of AMI. RESULTS: We expressed gelatinolysis activity as the ratio to MMP-2 standard. Mean gelatinase activity was 0.721+/-0.013. We divided patients into two groups, groups with gelatinolysis activity <0.72 (low group, n=27) and >0.72 (high group, n=25). Either change in LV end-diastolic volume index (LVEDVI, ml/m(2)) or end-systolic volume index (LVESVI, ml/m(2)) from admission to 2 weeks was not different between the two groups. Changes in both LVEDVI and LVESVI from 2 weeks to 6 months were greater in high gelatinolysis activity group than those in low activity group. Moreover, circulating level of gelatinolysis activity was positively correlated with changes in LVEDVI and LVESVI from 2 weeks to 6 months. CONCLUSION: These results demonstrate that circulating level of gelatinase activity can predict LV remodeling after AMI. Inhibition of gelatinase activity at the acute phase may be a therapeutic strategy for the prevention of remodeling after AMI.

Enalapril suppresses ventricular remodeling more effectively than losartan in patients with acute myocardial infarction.

BACKGROUND: Ventricular remodeling after acute myocardial infarction (AMI) is associated with increased morbidity and mortality. ELITE II study showed that losartan, an angiotensin receptor blocker, shows a survival benefit to the same degree as captopril, an angiotensin-converting enzyme inhibitor, does in patients with heart failure. However, recent OPTIMAAL study showed that clinical outcomes after losartan are not superior to those after captopril in patients with AMI. We examined the effect of losartan on ventricular remodeling after AMI comparatively with that of enalapril. METHODS: We enrolled 203 consecutive patients with AMI (mean age 62 +/- 11 years). All patients underwent primary percutaneous coronary intervention and were randomly assigned to losartan (25-50 mg, n = 101) or enalapril (2.5-10 mg, n = 102) treatment. Biplane left ventriculography was performed just after primary percutaneous transluminal coronary angioplasty (acute phase) and 6 months after the onset of AMI. RESULTS: Any of the maximal creatine kinase level, left ventricular end-diastolic volume index, end-systolic volume index, and ejection fraction measured at acute phase was not different between losartan and enalapril groups. However, changes in left ventricular end-diastolic index (18 +/- 25 vs 8 +/- 24 mL/m2) and left ventricular end-systolic volume index (10 +/- 20 vs 2 +/- 18 mL/m2) from acute phase to 6 months were significantly greater in losartan than in enalapril group. Change in left ventricular ejection fraction (0.2% +/- 10.3% vs 3.4% +/- 11.6%) from acute phase to 6 months was significantly smaller in losartan than in enalapril group. The plasma level of brain natriuretic peptide at 6 months was significantly higher in losartan than in enalapril group (all P < .05). CONCLUSION: These indicate that enalapril suppresses ventricular remodeling after AMI more effectively than losartan.

[Histological changes in the rabbit kidney induced by transarterial injection of a hypertonic sodium chloride solution].

PURPOSE: To evaluate histological changes in normal renal tissue induced by the injection of a hypertonic liquid. MATERIALS AND METHODS: Transarterial injection was performed in 17 healthy rabbits at various rates of infusion and amounts of isotonic and hypertonic (7%) sodium chloride solutions. In group 1, 10 cc of isotonic sodium chloride solution was injected. In groups 2 and 3, 1-10 cc of hypertonic solution was injected at rates of 1.0 cc/sec and 0.05 cc/sec, respectively. After 20 minutes of hemostasis, renal weight measurements and histological examinations were performed. In three rabbits that received 10 cc of 7% sodium chloride, lung samples were also obtained, and histological changes were reviewed. RESULTS: There was no tissue injury in group 1, and in groups 2 and 3 the histological changes for infusions of 4-10 cc were greater than those of 1-3 cc. There was no vascular endothelial cell damage in any case. None of the histological changes were dose dependent, and the lungs showed no clear histological alterations. CONCLUSION: Higher doses of a hypertonic sodium chloride solution cause irreversible histological changes in the rabbit kidney.

Nicorandil improves cardiac function and clinical outcome in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: role of inhibitory effect on reactive oxygen species formation.

BACKGROUND: Early reperfusion therapy improves the clinical outcomes of patients with acute myocardial infarction (AMI), but benefits are limited by reperfusion injury in some patients. We examined the effect of nicorandil, a hybrid of K(ATP) channel opener and nicotinamide nitrate, on reactive oxygen species (ROS) formation and clinical outcomes after primary percutaneous coronary intervention (PCI) for AMI. METHODS: Fifty-eight patients with AMI were randomized into control (n = 25) and nicorandil pretreatment groups (n = 33). In the nicorandil group, nicorandil (4 mg as a bolus injection followed by constant infusion at 8 mg/hour for 24 hours) was administered just after admission. ROS formation was assessed by measuring urinary excretion of 8-epi-prostaglandin F2alpha (PGF2alpha) and compared between the 2 groups. Cardiac function and the incidence of reperfusion injury and cardiac events were also compared. RESULTS: Urinary 8-epi-PGF2alpha excretion was increased 2-fold at 60 to 90 minutes after PCI in the control group, whereas it was unchanged after PCI in the nicorandil group (P <.0001 between the 2 groups). The incidence of no-reflow phenomenon was lower in the nicorandil group than in the control group. Left ventricular ejection fraction and cardiac index at 6 months were greater in the nicorandil group than in controls. Plasma brain natriuretic peptide level at 6 months was lower in the nicorandil group. Incidences of inhospital cardiac events and rehospitalization were lower in the nicorandil group than in controls. CONCLUSIONS: Nicorandil improves cardiac function and clinical outcomes in patients with AMI. Suppression of ROS formation may be involved in the mechanism.

Correlation of oxidative stress with activity of matrix metalloproteinase in patients with coronary artery disease. Possible role for left ventricular remodelling.

AIMS: Oxidative stress is implicated in the progression of heart failure, and matrix metalloproteinase (MMP) activity is increased in patients with congestive heart failure. We examined the role of oxidative stress on MMP activity in humans. METHODS AND RESULTS: We measured the MMP activity and the level of 8-iso-prostagandin F2alpha (8-iso-PGF2alpha), a specific and quantitative maker of oxidant stress, in the pericardial fluid (PF) in 47 consecutive patients with coronary artery disease who underwent coronary artery bypass surgery. Zymography of PF showed bands at 92-85kDa (MMP-9) and 72-65kDa (MMP-2). The MMP activity was expressed as the ratio to MMP-2 standard. MMP-2, MMP-9 and total gelatinolysis activities were positively correlated with left ventricular end-diastolic volume index (LVEDVI), and MMP-2 and total gelatinolysis activities were also positively correlated with LV end-systolic volume index. Moreover, MMP-2, MMP-9 and total gelatinolysis activities were all positively correlated with pericardial level of 8-iso-PGF2alpha. Also, LVDEVI was positively correlated with pericardial level of 8-iso-PGF2alpha. CONCLUSIONS: Oxidative stress may play an important role in the regulation of MMP activity. Augmented MMP activity may be involved in the development of ventricular remodelling in patients with coronary artery disease.

High plasma level of asymmetric dimethylarginine in patients with acutely exacerbated congestive heart failure: role in reduction of plasma nitric oxide level.

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is elevated in congestive heart failure (CHF) concomitantly with the higher levels of nitric oxide (NO) and cytokines. We investigated the association among ADMA, NO, and cytokines in human CHF. Blood was collected from 25 patients with acutely exacerbated chronic CHF (acute CHF, mean age 61 +/- 3 years), 23 patients with chronic compensated CHF (chronic CHF, mean age 62 +/- 2 years), and 26 control subjects (mean age 51 +/- 1 years). ADMA was measured by high-performance liquid chromatography. Tumor necrosis factor-alpha (TNF-alpha) was measured by enzyme-linked immunosorbent assay. Nitrate plus nitrite (NOx) was measured by the Griess method. The plasma levels of ADMA and TNF-Alpha were higher in patients with acute CHF than in those with chronic CHF and control subjects (both P < 0.05). The plasma level of NOx was higher in patients with chronic CHF than in those with acute CHF and control subjects (both P < 0.01). The plasma level of TNF-Alpha was positively correlated with that of ADMA in combination with patients with acute and chronic CHF (r = 0.31, P < 0.01). The plasma level of ADMA was, furthermore, negatively correlated with that of NOx (r = -0.29, P < 0.05). These findings indicate that ADMA is related to exacerbation of chronic CHF by suppression of the compensatory higher level of plasma NO.

Effect of allopurinol pretreatment on free radical generation after primary coronary angioplasty for acute myocardial infarction.

Allopurinol, an inhibitor of xanthine oxidase, was shown to improve the regional ventricular function after coronary artery occlusion and reperfusion in animal models. The effects of oral administration of allopurinol on a transient increase in free radical generation after primary percutaneous transluminal coronary angioplasty (PTCA) in patients with acute myocardial infarction (AMI) and on their clinical outcomes were examined. Thirty-eight AMI patients undergoing primary PTCA were randomly assigned to control (group 1, n = 20) and allopurinol treatment groups (group 2, n = 18). Allopurinol (400 mg) was administered orally just after the admission (approximately 60 min before reperfusion). Free radical production was assessed by successive measurement of urinary excretion of 8-epi-prostaglandin F(2alpha) (PGF(2alpha)) after PTCA. Urinary 8-epi-PGF(2alpha) excretion was increased by twofold at 60-90 min after PTCA compared with the baseline value in group 1. This increase was completely inhibited in group 2. Plasma allopurinol concentration was 1,146 +/- 55 ng/ml in group 2 when reperfusion was achieved. Slow flow in the recanalized coronary artery after PTCA occurred less frequently in group 2 than in group 1. Cardiac index determined just after reperfusion and left ventricular ejection fraction at 6 months after PTCA were both significantly greater in group 2 than in group 1 although pulmonary capillary wedge pressure was similar in the two groups. In conclusion, allopurinol pretreatment is effective in inhibiting generation of oxygen-derived radicals during reperfusion therapy and the recovery of left ventricular function in humans.