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PubMed2006

Stable transmission and expression of the hepatitis B virus total genome in hybrid transgenic mice until F10 generation.

The aim of the present study was the generation of transgenic mice carrying the complete Hepatitis B Virus (HBV) genome and investigation of the presence of Hepatitis B surface antigen (HBsAg) expression through successive generations. Transgenic mice were generated by microinjecting HBV genome into fertilized eggs. Integration and expression of HBsAg in transgenic mice were analyzed by genomic DNA PCR, Southern and slot blots and enzyme-linked immunosorbent assay (ELISA). Expression was also confirmed by Western blotting and RT-PCR. Histological changes in liver tissue of transgenic mice were examined by HE staining. The HBV genome was transmitted to the F10 generation and the presence of HBV X gene transcripts was confirmed by RT-PCR analysis using liver cDNAs from the F10 generation mice. During an observation period of 2.5 years, mice were sacrificed and their organs subjected to histopathological examination. In the liver, slight histopathologic alterations were observed but none of these lineages had any hepatocellular carcinoma (HCC). HBV DNA can be stably transmitted and expressed in the transgenic mice until F10 generation. However, although we showed the presence of X gene transcripts in liver tissues of F10 generation mice by RT-PCR in these animals, long-term expression of the HBV complete genome and expression of X protein in hepatocytes did not cause neoplasia during the life span and HCC. These transgenic mice should be useful for detailed studies of the replication and expression of HBV and for physiological studies of HBV genome.

Animals↗
PubMed1994

Superior displacement of the hip in total joint replacement: effects of prosthetic neck length, neck-stem angle, and anteversion angle on the moment-generating capacity of the muscles.

The purpose of this study was to determine the effects of superior displacement of the hip center and changes in three prosthetic parameters (neck length, neck-stem angle, and anteversion angle) on the capacity of muscles to generate force and moment about the hip. A three-dimensional model that calculates the maximum isometric forces and moments generated by 25 muscles crossing the hip over a wide range of body positions was used to evaluate the effects of a 2 cm elevation of the hip center and changes in the prosthetic parameters. After superior displacement of the hip center, the neck length was increased from 0 to 3 cm, the neck-stem angle was varied between 110 and 150 degrees, and the anteversion angle was varied between 0 and 40 degrees. Our analysis showed that a 2 cm superior displacement of the hip center would decrease the moment-generating capacity of the four muscle groups studied (abductors, adductors, flexors, and extensors) if neck length were not increased to compensate for decreased muscle length. In the computer model of an adult man that we used, a 2 cm increase in neck length restored the moment-generating capacity of the muscles by increasing muscle length and force-generating capacity. However, a 3 cm increase in neck length increased passive muscle forces substantially, which potentially could limit joint motion. An increased neck-stem angle (i.e. a valgus neck) decreased the abduction moment arm but increased the moment-generating capacity of the other muscle groups. A change in the anteversion angle from 0 to 40 degrees had a relatively small effect on the isometric moment-generating capacity of the muscles studied.

Biomechanical Phenomena↗
PubMed2002

Comparison of manual and computer-generated customized blocks for whole brain fields used in the treatment of medulloblastoma.

BACKGROUND: By using CT simulation and three-dimensional planning, we have developed a simple but accurate method of producing customized blocks for the cranial fields in the treatment of medulloblastoma. We compare here the margins and the volume of normal tissues included in the treatment volume with those obtained using blocks generated manually. PROCEDURE: Customized blocks for the whole brain field are generated using CT planning and autoblock function. The clinical target volume (CTV) is defined as the whole cerebrospinal fluid pathway, and the whole brain and spinal cord are contoured. A margin of 1.1 cm is generated using the autoblock function to account for set-up errors (3-5 mm) and penumbra (approximately 7 mm). A separate set of blocks was generated manually without the knowledge of the ones generated by the CT-simulator. These 2 sets of blocks were compared for a cohort of 7 consecutive patients. RESULTS: Overall, the manual blocks and the computer-generated blocks were quite similar. Those generated manually had more variations; they were always tighter (median of 6 mm tighter; range: 3-7 mm) at the level of the cribriform plate and in 5/7 patients were more generous (median of 6 mm more generous, range: 0-6 mm) at the temporal lobes. Dosimetric analysis showed that both methods provide adequate coverage of the CTV, with 100% of the CTV receiving > 95% of the prescribed dose for both. CONCLUSIONS: The customized block method for whole brain fields is simple to use and ensures adequate coverage of the target volume.

Cerebellar Neoplasms↗
PubMed1989

Structural features of isolated generative cells and their protoplasts from pollen of some liliaceous plants.

Large quantities of intact generative cells and their protoplasts were isolated from pollen protoplasts of four liliaceous plants, and their structural features were investigated. The generative cells, liberated from the vegetative cell cytoplasm of the pollen protoplasts, were initially spindle-shaped with two long, oppositely oriented extensions, and were surrounded by two cell membranes, one on each side of a wall of uniform thickness. The generative nuclei, stained with 4',6-diamidino-2-phenylindole (DAPI), showed ellipsoidal and highly condensed chromatin, whereas the generative cell cytoplasm, whose quantity was widely different from species to species, showed no fluorescence, suggesting the absence of plastid and mitochondrial DNA, although many mitochondria were present. The isolated generative cells, which were spindle-shaped at first, became spherical in shape in vitro. Immunocytochemistry and transmission electron microscopy revealed that this change was associated with the depolymerization of an axial array of microtubules present in generative cells in situ. These results are discussed in relation to the function of the generative cell within the bicellular pollen of angiosperms.

Cell Separation↗
PubMed2001

Whole body detection and imaging of nitric oxide generation in mice following cardiopulmonary arrest: detection of intrinsic nitrosoheme complexes.

Ischemic tissues generate nitric oxide (NO) by direct reduction of tissue nitrite under the acidic conditions that occur during ischemia. In view of the important implications of this enzyme-independent mechanism of NO generation on the pathogenesis and treatment of tissue injury, the NO formation in mice subjected to cardiopulmonary arrest was measured and imaged. Real-time measurement of NO generation was performed by detection of naturally generated NO-heme complexes in tissues using L-band electron paramagnetic resonance (EPR) spectroscopy. To distinguish NO generated from nitrite, animals were labeled with isotopically enriched (15)N-nitrite. Mice were infused with nitrite (70 mg/kg, intravenous), cardiopulmonary arrest induced by an overdose of phenobarbital, and transferred to the EPR resonator. Measurements of NO generation were performed on the intact animal at the levels of the head, thorax, and abdomen. At the end of 3 hr, major organs were isolated and analyzed for their NO signal. The NO complexes were found to have maximum levels in lung, heart, and liver. Three-dimensional spatial mapping of the NO complex in the intact animal subjected to cardiopulmonary arrest was performed using EPR imaging techniques. The images also confirmed the maximum formation in the lungs, heart, and liver. The present data reveal that mice subjected to cardiopulmonary arrest generate large amounts of NO, which is nitrite mediated. The observed signal was largely due to heme-bound NO, which accounted for the high concentrations found in these organs. This increased NO formation during cardiopulmonary arrest could contribute to the difficulty of resuscitation after long periods of arrest. Magn Reson Med 45:700-707, 2001.

Animals↗
PubMed1994

Generation of free radicals from neocarzinostatin mediated by NADPH/cytochrome P-450 reductase via activation of enediyne chromophore.

Neocarzinostatin (NCS) is one of the most potent antitumor agents. It contains a chromophore of a unique enediyne structure as its prosthetic group. Here, we report the generation of free radicals from NCS by the NADPH/cytochrome (cyt) P-450 reductase system. Free radical species, which were generated in the reaction mixture of NCS/NADPH/cyt P-450 reductase, were identified by using electron spin resonance spin trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The spin adducts of superoxide and hydroxyl radical (DMPO-OOH and DMPO-OH, respectively) were generated in the reaction of NCS with the NADPH/cyt P-450 reductase system. From kinetic analyses of DMPO-OOH generation as a function of the concentration of NCS, the Vmax/Km value of the reaction was 0.4 x 10(6) M-1min-1. In addition, we identified thiyl radical generation in this system in the presence of glutathione. These results indicate that NCS is a potent generator of free radicals in cells where cyt P-450 reductase is available. Moreover, it seems that free radicals, generated by enzymatic activation of NCS, are involved in cytotoxicity of NCS as well as in DNA damage.

Animals↗
PubMed1997

The mechanisms of compound 48/80-induced superoxide generation mediated by A-kinase in rat peritoneal mast cells.

This investigation was undertaken to clarify the mechanisms of superoxide anion (O2-) generation in rat peritoneal mast cells. Compound 48/80, a typical histamine liberator mediated by calcium influx, elicited O2- generation from the mast cells in a dose-dependent fashion. It was demonstrated by immunohistochemical study and Western blot analysis that the mast cells contained the 47-kDa phagocyte oxidase (p47phox) protein, which was one cytosolic component of the NADPH oxidase system. Arachidonic acid stimulated O2- generation in the mast cells, but other unsaturated fatty acids had no effect. On the other hand, 48/80-induced O2- generation was inhibited by phospholipase A2 inhibitors, such as arachidonyl trifluoromethyl ketone and manoalide. Forskolin, isoprenaline, and dibutyryl cyclic AMP inhibited the O2- generation, and KT-5720, a cyclic AMP-dependent protein kinase (A-kinase) inhibitor, markedly enhanced the O2- generation. These findings suggest that O2- is generated by a NADPH oxidase-like enzyme system in mast cells and that this enzyme system is activated by arachidonic acid released by cytosolic phospholipase A2. Thus, it is regulated by the cyclic AMP-A kinase system.

Animals↗
PubMed2001

Structural mechanisms of drug resistance for mutations at codons 181 and 188 in HIV-1 reverse transcriptase and the improved resilience of second generation non-nucleoside inhibitors.

Mutations at either Tyr181 or Tyr188 within HIV-1 reverse transcriptase (RT) give high level resistance to many first generation non-nucleoside inhibitors (NNRTIs) such as the anti-AIDS drug nevirapine. By comparison second generation inhibitors, for instance the drug efavirenz, show much greater resilience to these mutations. In order to understand the structural basis for these differences we have determined a series of seven crystal structures of mutant RTs in complexes with first and second generation NNRTIs as well as one example of an unliganded mutant RT. These are Tyr181Cys RT (TNK-651) to 2.4 A, Tyr181Cys RT (efavirenz) to 2.6 A, Tyr181Cys RT (nevirapine) to 3.0 A, Tyr181Cys RT (PETT-2) to 3.0 A, Tyr188Cys RT (nevirapine) to 2.6 A, Tyr188Cys RT (UC-781) to 2.6 A and Tyr188Cys RT (unliganded) to 2.8 A resolution. In the two previously published structures of HIV-1 reverse transcriptase with mutations at 181 or 188 no side-chain electron density was observed within the p66 subunit (which contains the inhibitor binding pocket) for the mutated residues. In contrast the mutated side-chains can be seen in the NNRTI pocket for all seven structures reported here, eliminating the possibility that disordering contributes to the mechanism of resistance. In the case of the second generation compounds efavirenz with Tyr181Cys RT and UC-781 with Tyr188Cys RT there are only small rearrangements of either inhibitor within the binding site compared to wild-type RT and also for the first generation compounds TNK-651, PETT-2 and nevirapine with Tyr181Cys RT. For nevirapine with the Tyr188Cys RT there is however a more substantial movement of the drug molecule. We conclude that protein conformational changes and rearrangements of drug molecules within the mutated sites are not general features of these particular inhibitor/mutant combinations. The main contribution to drug resistance for Tyr181Cys and Tyr188Cys RT mutations is the loss of aromatic ring stacking interactions for first generation compounds, providing a simple explanation for the resilience of second generation NNRTIs, as such interactions make much less significant contribution to their binding.

Binding Sites↗
PubMed1997

Superoxide generation by renal proximal tubule nitric oxide synthase.

Lipid A, the biologically active component of lipopolysaccharide, initiates a specific cytotoxic signaling cascade in the renal proximal tubule that involves a rapid release of intracellular calcium, the activation of nitric oxide synthase (NOS) and NO production. Superoxide (O2-) generation is also a component of this cascade and both NO and O2- are required for the development of oxidant stress and cytotoxicity. Here we examined whether NOS activity was responsible for O2- generation. In renal proximal tubules isolated from the rat, the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA) but not D-NMMA blocked lipid A (50 microg/ml)-stimulated O2- generation as measured by the reduction of cytochrome c during a 30-min incubation period. When L-arginine (2 mM) was added to the tubule suspensions, O2- generation was significantly inhibited, while NO2- (a marker of NO generation) was significantly increased. The addition of L-arginine also reduced lipid A-stimulated malondialdehyde formation at 30 min (a marker of lipid peroxidation) and lactate dehydrogenase release at 90 min (a marker of cell death). Thus, lipid A-stimulated the generation of both NO and O2- via NOS activation. Furthermore, increasing L-arginine availability shifted NOS activity toward NO generation and reduced oxidant injury. These results offer an explanation of why scavengers of NO or oxygen radicals ameliorate endotoxin-induced acute renal failure in vivo.

Analysis of Variance↗
PubMed2005

Higher harmonic generation microscopy.

Higher harmonic-generation, including second harmonic generation and third harmonic generation, leaves no energy deposition to the interacted matters due to its virtual-level transition characteristic, providing a truly non-invasive modality and is ideal for in vivo imaging of live specimens without any preparation. Second harmonic generation microscopy provides images on stacked membranes and arranged proteins with organized nano-structures due to the bio-photonic crystalline effect. Third harmonic generation microscopy provides general cellular or subcellular interface imaging due to optical inhomogeneity. Due to their virtual-transition nature, no saturation or bleaching in the generated signal is expected. With no energy release, continuous viewing without compromising sample viability can thus be achieved. Combined with its nonlinearity, higher harmonic generation microscopy provides sub-micron three-dimensional sectioning capability and millimeter penetration in live samples without using fluorescence and exogenous markers, offering morphological, structural, functional, and cellular information of biomedical specimens without modifying their natural biological and optical environments.

Equipment Design↗
PubMed1989

Ontogeny of inflammatory cell responsiveness: superoxide anion generation by phorbol ester-stimulated fetal, neonatal, and adult bovine neutrophils.

Newborn calves, like human infants, are uniquely susceptible to bacterial infections. Part of this increased susceptibility may be related to defects in newborn polymorphonuclear leukocyte (PMN) defensive functions. It remains unclear whether reported deficits in newborn PMN function represent maturational disorders or are manifestations of some form of perinatal suppression phenomenon. We therefore compared the ability of bovine newborn PMNs (less than 24 h old), newborn PMNs (7-10 days of age), fetal PMNs (210-220 days gestational age), and adult PMNs to generate superoxide anion (O2-) as an indicator of respiratory burst activity. Citrated blood was collected, and PMNs were isolated to greater than 95% purity and 98% viability. O2- generation was measured as the superoxide dismutase-inhibitable (10 micrograms/ml) reduction of ferricytochrome c (2 mg/ml) after activation of PMNs with phorbol myristate acetate (PMA, 2 micrograms/ml) to directly stimulate protein kinase C. The reaction kinetics were measured (37 degrees C, 550 nm) using a spectrophotometer and chart recorder for continuous monitoring. O2- generation was measured for 5 min after the initial lag period and the total nanomoles of O2- generated calculated using the extinction coefficient for ferricytochrome c. Newborn PMNs (N = 10) generated significantly less O2- (5.7 +/- 0.8 nmol O2-/10(6) cells/5 min, P less than 0.01) than did adult PMNs (N = 14) (9.6 +/- 2.1 nmol O2-/10(6) cells/5 min) or fetal PMNs (N = 4) (10.7 +/- 0.7 nmol O2-/10(6) cells/5 min). PMNs from 7- to 10-day-old calves (N = 9) generated almost identical amounts of O2- as newborn PMNs (5.7 +/- 1.6 nmol O2-/10(6) cells/5 min). There was no difference in measured lag time period between newborn and adult PMNs, but fetal PMNs had significantly reduced (P less than 0.01) mean lag time. The data indicated that bovine newborn PMNs have a decreased ability to generate O2- in response to PMA stimulation, which persists for at least 7-10 days, and that this functional decrement may be a manifestation of some form of perinatal PMN suppression phenomenon rather than a developmental abnormality since fetal PMNs produced O2- as well as adult PMNs.

Animals↗
PubMed1995

Cyclic GMP generation mediated by 5-HT-2 receptors via nitric oxide-dependent pathway and its effect on the desensitization of 5-HT-2 receptors in C6 glioma cells.

Serotonin (5-HT)-2 receptor-mediated cGMP generation was investigated in comparison with calcium (Ca2+) mobilization in C6 glioma cells. 5-HT enhanced cGMP generation, and risperidone and ketanserin potently blocked the response. These results indicate that 5-HT-2 receptors are responsible for the cGMP generation. 5-HT-induced cGMP production was completely abolished by BAPTA, an intracellular Ca2+ chelating agent, or NG-mono-methyl-L-arginine(NMMA), a nitric oxide synthase (NOS) inhibitor, suggesting that 5-HT-induced cGMP generation was through nitric oxide (NO)-dependent pathway. 5-HT (10 microM)-elicited Ca2+ mobilization and cGMP generation were reduced to 40 and 15% after pretreatment with 10 microM 5-HT for 4 hours. NMMA did not modify 5-HT-induced desensitization of either Ca2+ mobilization or cGMP generation, suggesting that NO pathway is independent of the desensitization. The present study has demonstrated the nature of 5-HT-2 receptor-mediated cGMP generation in C6 glioma cells.

Animals↗
PubMed1996

Influence of triacylglycerol structure and fatty acid profile of dietary fats on milk triacylglycerols in the rat. A two-generation study.

We investigated the influence of dietary fatty acid profile and triacylglycerol structure on the fatty acid profile and triacylglycerol structure of milk lipids in two generations of rats. Three groups of rats received diets containing 20% fat of which approximately 20% was n-3 fatty acids located in different positions of the triacylglycerol: a fish oil-based diet [docosahexaenoic acid (22:6n-3) predominantly in the sn-2 position], a seal oil-based diet (22:6n-3) predominantly in the sn-1/sn-3 position, or a plant oil-based diet [alpha-linolenic acid (18:3n-3) distributed evenly between the three positions]. This design allowed us to investigate (i) the effect of the triacylglycerol structure of the dietary fat; (ii) the effect of receiving the n-3 fatty acids as long-chain derivatives or as the precursor, 18:3n-3; and (ii) the long-term effects over two generations. The fatty acid profiles of the milk lipids largely reflected the diets, but in the second generation, the level of medium-chain fatty acids was higher (P < 0.05) in the milk from rats fed the fish oil diet (24%) compared with the other dietary groups (15 and 18%). This suggests an increased endogenous synthesis of fatty acids in the mammary glands of the fish oil-fed rats. The levels of long-chain n-3 fatty acids in milk were higher (P < 0.05) in rats fed marine oils (8-12%) compared with rats fed vegetable oil (1%) in both generations. The level of long-chain n-3 fatty acids was significantly higher in the milk from the fish oil-fed rats (12.3%) compared to the seal- oil fed rats (8.0%) in the first generation, but not in the second generation (8.9 vs. 9.1%). The general structure of milk triacylglycerols was maintained in the three experimental groups with 16:0 acylated in the sn-2 position and 18:1 in the sn-1/sn-3 positions. The triacylglycerol structure of mammalian milk appears to be conserved even during extreme dietary manipulation over two generations and an extensive enrichment with long-chain n-3 polyunsaturated fatty acids requires their presence in the diet.

Animals↗
PubMed1997

["Single generator distortion products"(sgDPOAE). Precise measurements of distortion product otoacoustic emissions by three-tone stimulations].

Distortion product otoacoustic emissions (DPOAE) are generated undoubtedly in the region of overlap between the two travelling waves of primaries f1 and f2 (the "primary" generator). Since DPOAE lead to a psychoacoustic perception, it is suspected that the cochlear amplifier is additionally activated at place 2f1-f2 (the "secondary" generator) leading to a stimulus frequency emission (SFOAE). In suppression experiments we demonstrated that a suppressor tone 25 Hz above the frequency of the postulated secondary generator alters DP-amplitude depending (1) on the DP-gram fine structure and (2) the sound pressure level of the suppressor (-20 to 80 dB SPL). At a maximum of the fine structure, low suppressor levels (< 50 dB SPL) reduced the DP-amplitude, whereas an increase occurred at a minimum. Intermediate suppressor levels (50-60 dB SPL) always clamped the DP-amplitude and extinguished the DP-gram fine structure. Our results support the hypothesis that conventional DPOAE, which are measured in the external ear canal, are the result of an interference of the primary and secondary generator. Depending on the relative phase between the two emissions, a constructive and a destructive interference of the two signals results in an emission pattern which closely resembles the DP-gram fine structure. When the secondary generator is suppressed by intermediate suppressor levels, DPOAE amplitude depends only on the status of the cochlear amplifier near f2. These emissions we call "single generator" DPOAE (sgDPOAE).

Acoustic Impedance Tests↗
PubMed2004

Internally generated and externally triggered actions are physically distinct and independently controlled.

In everyday life we must constantly balance our intentions to act in a certain way with reactions that are imposed upon us by the outside world. Recent neuroimaging studies have examined these classes of movement separately but despite the fundamental requirement for us to efficiently organize our internally generated and externally triggered actions, few studies have examined the relationship between these two classes of movement. We measured EMG activity in the right first dorsal interosseous while subjects performed right index finger key presses either in an internally generated condition or an externally triggered condition. In addition, in an attempt to probe the relationship between the processing underlying these two types of action, we examined the effect on reaction time (RT) and EMG activity in a third "truncation" condition in which subjects were forced to switch from an intentional (internally generated) mode of response production to an externally triggered mode. Results indicated significantly greater muscle activation for actions that were internally generated as compared to externally triggered. Truncation caused responses to be delayed by, on average, 54.7 ms as compared with simple externally triggered responses, suggesting that the motor system cannot take advantage of preexisting levels of preparation when switching between internally generated and externally triggered actions. Interestingly, the unique EMG signatures of internally generated and externally triggered actions were preserved in truncation. Thus, subjects switched between the two types of action rather than simply modifying an ongoing action. The results provide peripheral physiological support for previous neuroimaging work suggesting that internally generated actions are preceded by greater levels of preparation than externally triggered actions. The present findings also raise the interesting possibility that the motor system processes these two classes of action separately even though the motor output required is the same.

Adult↗
PubMed2000

Mental stress and physical exercise increase platelet-dependent thrombin generation.

Thrombin generation is an important factor in the pathogenesis of thrombogenic disorders and acute coronary syndromes. Increase in mental stress has been associated with the initiation of the acute coronary syndromes, but the exact mechanism is not known. The present study examined the effects of physical exercise and mental stress on platelet-dependent thrombin generation. Twelve healthy men (mean age 34.2 +/- 2.4 years) underwent a treadmill exercise test and a mental stress test by performing mental arithmetic. Platelet-dependent thrombin generation and plasma concentrations of catecholamines, thrombin-antithrombin III complex (TAT), plasmin-alpha2 plasmin inhibitor complex (PIC), and plasminogen activator inhibitor-1 (PAI-1) were measured before, immediately after, and at 10 and 30 min after stress. Thrombin generation increased significantly immediately after exercise, followed by rapid normalization. Mental stress caused a significant increase in thrombin generation 10 min after stress. While plasma concentrations of epinephrine, norepinephrine, and dopamine were elevated immediately after exercise, and rapidly returned to baseline, only plasma norepinephrine increased immediately after mental stress. TAT and PIC concentrations did increase immediately after exercise; however, PAI-1 remained unchanged. The increase in thrombin generation with exercise and mental stress was unaffected by treatment with 81 mg/day of aspirin of 7 days. However, it was inhibited by a single oral 40-mg dose of metoprolol. Both exercise and mental stress cause an increase in platelet-dependent thrombin generation, which was suppressed by beta-blocker therapy, but not by aspirin.

Adrenergic beta-Antagonists↗
PubMed1998

[Therapy with implanted cardioverter-defibrillator: Is a replacement of the impulse generator due to battery depletion also necessary without the occurrence of a tachyarrhythmia episode?].

The aim of this retrospective study was to evaluate the necessity of the replacement of an implantable cardioverter/defibrillator (ICD) in patients with pulse generator battery depletion without an adequate, spontaneous arrhythmia episode during the life-time of the first implanted device. In this study 213 patients with implanted ICDs were enrolled. In 62 patients an elective generator replacement due to battery depletion was performed. Both patient groups (Group A: patients with generator replacement n = 62 and Group B: patients without replacement n = 151) were not different with regard to main clinical characteristics, such as underlying heart disease and left ventricular function. In both groups there was a predominance of male patients (Group A: 89%; Group B: 83%). The mean age was 58 +/- 11 years and 59 +/- 11 years in Group A and Group B, respectively. Coronary artery disease was present in 66% and 68% of the patients. There was a comparable left ventricular ejection fraction: Group A: 30.5 +/- 9% vs Group B: 31.9 +/- 9%. The follow-up time was much longer in Group A patients compared to Group B patients (50.5 +/- 14 vs. 16.5 +/- 11 months). For the total patient group there was a 5 year event-free probability of 23%, no differences were found between both groups. The subanalysis in Group A patients revealed no difference in the probability of ICD-shock occurrence prior to or after the replacement of the pulse generator. In 48/62 (77%) of Group A patients adequate ICD discharges were documented. In 15/62 (24%) patients shock occurred before and after generator replacement. In 6/62 (10%) of Group A patients, the first adequate ICD-therapy was documented after generator replacement. The results of this study indicate the necessity of an ICD-pulse generator replacement even in patients without an adequate device discharge during the life-time of the first implanted device.

Aged↗
PubMed2000

Generation of reactive oxygen species by Candida albicans in relation to morphogenesis.

Candida albicans is able to generate significant amounts of reactive oxygen species (ROS). In this study, ROS generation by yeast and hyphal forms of the strain 3153 A was analyzed to determine whether ROS generation could be a major factor in the invasive behavior of germinative cells. Furthermore, the virulent strain CA6 and its avirulent and agerminative mutant VIR3 were compared. ROS were measured by lucigenin-enhanced chemiluminescence and a cytochrome c assay. During the blastoconidial phase of all strains moderate amounts of ROS were found at cell concentrations > 1 x 10(5)/ml. However, ROS generation appeared to be specifically inhibited at cell concentrations > 1 x 10(8)/ml, and this was found in both assays. As shown in comparative experiments, the medium used for measurement markedly affected the total amount of ROS. Hyphae of strain 3153 A generated a significantly higher amount of ROS than yeast cells and cells with germ tubes (P < 0.001). The strain CA6 showed significantly higher ROS generation than the VIR3 strain for both blastoconidiae and after 30 min of induction of hypha formation (P < 0.05). In conclusion, hypha formation, usually acknowledged as a major factor in Candida pathogenicity, was associated with markedly increased ROS formation. ROS generation was not closely linked to the ability to form hyphae, but was highest in germinative cells.

Candida albicans↗