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K Fukuchi

Publications and source records attributed to K Fukuchi.

At least 73 records · Page 4Linked to original sources
PubMed1998

Amyloid-beta deposition in skeletal muscle of transgenic mice: possible model of inclusion body myopathy.

Inclusion body myopathy is a progressive muscle disorder characterized by nuclear and cytoplasmic inclusions and vacuolation of muscle fibers. Affected muscle fibers contain deposits of congophilic amyloid, amyloid-beta immunoreactive filaments, and paired helical filaments, all of which are pathological hallmarks of Alzheimer's disease in brain. Accumulations of amyloid-beta and its precursor are thought to play important roles in the pathogenesis of both inclusion body myopathy and Alzheimer's disease. Overexpression of mutant forms of beta protein precursor in transgenic mice by neuron-specific promoters has been reported to cause amyloid deposits in the brain. Here we report that overexpression in transgenic mice of the signal plus 99-amino acid carboxyl-terminal sequences of beta protein precursor, under the control of a cytomegalovirus enhancer/beta-actin promoter, resulted in vacuolation and increasing accumulation of the 4-kd amyloid-beta and the carboxyl-terminus in skeletal muscle fibers during aging. These deposits in transgenic muscle only rarely showed Congo red birefringence. Thus, overexpression of part of beta protein precursor in transgenic mice led to development of some of the characteristic features of inclusion body myopathy. These mice may be a useful model of inclusion body myopathy, which shares a number of pathological markers with Alzheimer's disease.

Age Factors↗
PubMed1998

Decreased hippocampal blood flow related to memory impairment after cardiovascular surgery: assessment by reconstructed SPECT parallel to the longitudinal axis of the hippocampal formations.

Hippocampal damage has been linked to memory impairment. To clarify the relationship between decreased hippocampal blood flow and memory impairment in patients after cardiovascular surgery, the authors compared Tc-99m HMPAO SPECT findings and Mini Mental State Examination (MMSE) scores. Eight patients who had valve replacement, two who underwent aorto-coronary bypass, two who had aortic aneurysm replacement and one who had a ventricular septal defect closure were included in this study. Cerebral perfusion was estimated using reconstructed tomographic images, which were parallel to the longitudinal axis of the hippocampal formations. The hippocampal uptake ratios of Tc-99m HMPAO were calculated and normalized to that of the cerebellum. In three patients whose MMSE score decreased after surgery, the hippocampal uptake ratio was significantly reduced (0.69 +/- 0.09) compared with the remaining 10 patients whose MMSE scores did not decrease after surgery (0.91 +/- 0.02). These data suggest that SPECT imaging parallel to the longitudinal axis of the hippocampus is sensitive to decreased hippocampal blood flow, and decreased hippocampal blood flow is related to memory impairment in some patients after cardiovascular surgery.

Adolescent↗
PubMed1998

Comparison of dual-isotope acquisition of 201Tl and 99Tcm-tetrofosmin for the detection of ischaemic heart disease and determination of the optimal imaging time of 99Tcm-tetrofosmin.

Comparative studies of thallium-201 (201Tl) and 99Tcm-tetrofosmin for the detection of ischaemic heart disease (IHD) have previously been reported. These 201Tl and 99Tcm-tetrofosmin studies were usually performed separately with different exercise loads at an interval of several days. Here, we used a dual-isotope technique with exercise myocardial SPET (single photon emission tomography) in 17 patients with IHD and 10 patients with normal coronary arteries. The triple-energy window (TEW) method was applied for cross-talk correction. SPET imaging was performed at 10 and 70 min (S1 and S2) after the injection of 99Tcm-tetrofosmin (222 MBq) and 201Tl (74 MBq) at peak exercise to determine the optimal imaging time of 99Tcm-tetrofosmin. The S2 value was obtained 35 min after the subject drank a glass of milk to accelerate hepatobiliary clearance. Twenty-five minutes after S2, 37 MBq of 201Tl were reinjected at rest and SPET imaging (S3) was performed. Immediately after S3, 666 MBq of 99Tcm-tetrofosmin were reinjected and SPET imaging (S4) was performed 50 min later. Representative short and vertical long axis tomograms were divided into 17 segments. Each segment was assessed using a 4-point scoring system. The defect score was defined as the sum of each segmental score. The defect scores for imaging at exercise were 14.3 +/- 11.4 for 201Tl at S1, 11.4 +/- 8 for 99Tcm-tetrofosmin at S1 and 9.7 +/-9.8 for 99Tcm-tetrofosmin at S2 (P < 0.01), respectively. The washout rate of 99Tcm-tetrofosmin for the first hour was 15.5 +/- 7.3% and 11.8 +/- 7.7% (P < 0.01), respectively, for the normal and ischaemic segments. The image quality of 201Tl at S1 was almost equivalent to that of 99Tcm-tetrofosmin at S1/S2. The overall sensitivity and specificity for the detection of ischaemia was 94% and 82% for 201Tl at S1, 89% and 86% for 99Tcm-tetrofosmin at S1, and 88% and 95% for 99Tcm-tetrofosmin at S2, respectively. The overall accuracy was 86%, 88% and 92%, respectively. The myocardial viability score was 7.4 +/- 7.1 for 201Tl at S3 and 5.8 +/- 7.0 for 99Tcm-tetrofosmin at S4 (P < 0.01). The results indicate that the diagnostic accuracy of 99Tcm-tetrofosmin for myocardial ischaemia is almost equivalent to that of 201Tl as assessed by dual SPET imaging, and that the optimal imaging time for 99Tcm-tetrofosmin is within 10-35 min (S1) after exercise.

Coronary Disease↗
PubMed1998

Baumkuchen map analysis to detect postural cerebral hypoperfusion with upright 99Tcm-HMPAO brain SPET.

We have evaluated a polar cortical flow Baumkuchen map (BK map), constructed from projection data by inwardly layering cortical flow stripes from the base to the apex, to detect postural cerebral hypoperfusion using 99Tcm-HMPAO brain SPET. A circular cortical perfusion outline was constructed from sinogram data at a 20% threshold; a ring was then formed by constructing an inner line with a radius equal to half that of the outer line. This ring on the transaxial image was superimposed onto the cortical image, then divided into 60 portions at 6 degrees intervals from the centre. The maximal number of counts per pixel within each sector was determined, translated into polar coordinate profiles and displayed as a polar map. We studied 11 patients with unilateral stenosis of the internal carotid artery or middle cerebral artery (MCA) and 7 patients without stenosis, using upright and supine (rest) 99Tcm-HMPAO brain SPET Cerebral perfusion was visibly altered on the BK maps of all 11 patients with arterial stenosis and on the transaxial images of 8 of them. A semi-quantitative analysis of the BK maps using a ratio of the counts in the regions of interest over the right and left MCA areas, showed that the mean of the ratios was significantly lower in the upright images than in the upright + rest and rest images (P = 0.0044 and 0.0033, respectively). Although the difference in the means of the ratios between the upright and upright + rest images was significant for both the BK map and transaxial image data (P = 0.0044 and 0.0051, respectively), the BK map was accurate in detecting changes in perfusion in the upright position. We conclude that BK map analysis is useful for detecting changes in patients examined using upright brain SPET.

Adult↗
PubMed1998

[Imaging of myocardial perfusion and metabolism with positron emission tomography].

Positron emission tomography (PET) has been providing new information in the diagnosis and the pathophysiological assessment of heart diseases. The PET tracers commonly used in Japan are 13N-ammonia, 18F-fluorodeoxyglucose (FDG) for imaging of myocardial perfusion and metabolism, respectively. Measurement of regional myocardial blood flow by 13N-ammonia dynamic PET scan and a compartment model analysis is applied to the functional estimation of coronary stenotic lesions and the detection of perfusion abnormalities in hypertrophic heart diseases, familial hyperchlesterolemia and other diseases with possible microvascular lesions. 18F-FDG is commonly used to differentiate ischemic but viable tissue from myocardial scar in coronary artery disease and also used to detect cardiac tumor and the cardiac involvement in sarcoidosis. In addition to these two tracers, 11C-acetate is now expected to provide the clinical analysis of pathophysiology of heart failure by estimating the efficiency of energy conversion of the heart into external work.

Acetates↗
PubMed1998

[Usefulness of ECG-gated 99mTc-MIBI myocardial SPECT in the follow-up study of patients with acute myocardial infarction].

To clarify the background of the scintigraphic improvement in non-gated myocardial perfusion imaging for patients with acute myocardial infarction, we performed serial ECG-gated 99mTc-MIBI myocardial SPECT in 17 patients with acute myocardial infarction (AMI) receiving successful reperfusion therapy. ECG-gated myocardial SPECT and left ventriculography were performed at 1 week (acute phase) and 1 month (subacute phase) after the onset of AMI. Regional %uptake (regional count x 100/maximal count) was determined for each of 8 myocardial segments of the Bull's eye map. We analyzed the data in 53 AMI segments out of total 136 myocardial segments, on the non-gated (NG), end-diastolic (ED), and end-systolic (ES) images. In addition, the delta %uptake (%uptake in subacute phase--%uptake in acute phase) was also determined as an index representing the improvement of myocardial tracer uptake on each image. In 17 segments (group A) with wall motion recovery assessed by serial left ventriculography, the %uptake on the NG image was significantly improved (61.6 +/- 10.0 to 75.7 +/- 10.1, p < 0.0001). However, in 36 segments (group B) without wall motion recovery, the change of %uptake on the NG image was small. There was no significant change in the %uptake on the ED image in groups A and B. On the contrary, the %uptake on the ES image showed a significant increase in group A (58.4 +/- 11.8 to 68.9 +/- 11.8, p < 0.001), but did not in group B. Thus, this change on the ES image reflects the wall motion recovery. Furthermore, in group A, there was a significant correlation between the delta %uptake on the NG image and those on the ES image (p < 0.02), but was not between those on the NG and the ED images. Thus, the change in the %uptake on the NG image was more related to those on the ES image which is more affected by the change in regional wall motion than those on the ED image which reflects improved myocardial perfusion. These results suggest that ECG-gated myocardial 99mTc-MIBI SPECT is more useful to assess the serial change in myocardial perfusion and contraction than the conventional non-gated SPECT in the follow-up study of patients with AMI.

Aged↗
PubMed1998

Iodine-123-iomazenil and iodine-123-iodoamphetamine SPECT in major cerebral artery occlusive disease.

UNLABELLED: Iodine-123-iomazenil (IMZ) is a SPECT ligand for central-type benzodiazepine receptors, which are located only on neurons. We evaluated the feasibility of using IMZ SPECT for identifying neuronal damage in patients with the chronic phase of thrombotic cerebral ischemia. METHODS: We studied 15 patients with angiographically-confirmed unilateral severe occlusive lesions (occlusion or > 70% stenosis) in the carotid system. IMZ SPECT images obtained 180 min after injection of 167-222 MBq IMZ were analyzed. The regional cerebral blood flow and perfusion reserve were evaluated for comparison with IMZ SPECT findings, using the split-dose 123I-iodoamphetamine (IMP) SPECT method, coupled with intravenous injection of 1 g acetazolamide. On both SPECT images, the count ratio of the affected to the nonaffected whole MCA territory (A/NA ratio) and of the contralateral to the ipsilateral cerebellar cortex (C/I ratio) were determined. RESULTS: The A/NA ratio with IMZ was significantly higher than that with IMP (94.5% +/- 6.2% versus 91.4% +/- 6.6%, p < 0.005), although a significantly positive correlation was found between these two ratios (r = 0.854, p < 0.0001). The C/I ratio with IMP was decreased significantly in 5 patients compared with that in normal subjects, whereas the C/I ratio with IMZ was decreased in only 1 patient. There was no significant correlation between the A/NA ratio with IMZ and the perfusion reserve in the affected MCA territory. In 2 of 5 patients with a decreased A/NA ratio (<90%) with IMZ, decreased blood flow with preserved perfusion reserve and cerebral hemispheric atrophy were observed, which suggested the influence of neuronal loss due to chronic ischemia. CONCLUSION: These findings indicate that IMZ SPECT, which provides new information regarding neuronal damage after ischemic insult to the brain, is useful for evaluating thrombotic cerebral ischemia.

Amphetamines↗
PubMed1998

Impaired regional fatty acid uptake and systolic dysfunction in hypertrophied right ventricle.

UNLABELLED: Little information is available regarding the determinants of systolic contractile function of the hypertrophied right ventricle (RV). The purpose of this study was to clarify the relationship between myocardial metabolism and contractile function in the hypertrophied RV due to pulmonary hypertension (PH). METHODS: Iodine-123-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-sestamibi (MIBI) SPECT were performed to calculate the RV-to-left ventricle (LV) tracer uptake ratio (RV/LV) in 21 patients with PH (6 with primary PH and 15 with chronic thromboembolic PH). The patients also underwent electron-beam CT to assess RV ejection function (RVEF) and percentage systolic wall thickening (%SWT) and right heart catheterization to measure mean pulmonary arterial pressure (mPAP). RESULTS: There were significant positive correlations between mPAP and MIBI-RV/LV (r = 0.89, p < 0.001) and between mPAP and BMIPP-RV/LV (r = 0.86, p < 0.001). However, 8 patients showed lower BMIPP-RV/LV than MIBI-RV/LV, indicating the impairment of myocardial fatty acid uptake in the RV. These patients had lower RVEF and %SWT compared to those with normal myocardial fatty acid uptake (RVEF = 28% +/- 10% compared to 40% +/- 9% and %SWT = 33% +/- 27% compared to 74% +/- 30%, respectively; p < 0.05 for both comparisons). Although mPAP did not differ between the groups, the RVEF-mPAP and %SWT-mPAP regression lines drawn from the patients with impaired myocardial fatty acid uptake were located below the lines from the patients with normal myocardial fatty acid uptake, suggesting disproportionately decreased RV myocardial contractility for a given mPAP in patients with impaired myocardial fatty acid uptake. The patients with the impaired fatty acid uptake in the RV had a significantly higher death rate (log-rank test, p < 0.05). CONCLUSION: The results from this preliminary study suggest that myocardial fatty acid uptake is impaired in the failing hypertrophied RV due to PH.

Fatty Acids↗
PubMed1998

[Occurrences of penicillin-binding protein 2B gene in clinically isolated penicillin-resistant Streptococcus pneumoniae].

We analyzed 88 strains of Streptococcus pneumoniae (S. pneumoniae) isolated in Showa University Hospital from June 1995 to July 1996. The ratios of antibiotic resistance were 39% to penicillin G, 50% to erythromycin, and 2% to imipenem. No resistant to cefotaxime and ofloxacin was observed. Thirty-four strains (39%) were considered to be penicillin-resistant S. pneumoniae (PRSP) strains (MIC of penicillin G > or = 0.5 microgram/ml), according to the breakpoint determined by the Japanese Working Group for Penicillin-Resistant Streptococcus pneumoniae. The ratio of PRSP was higher in S. pneumoniae isolated from inpatients (25/47) when compared to that from outpatients. By PCR analysis, DNA regions of autolysin were amplified in all the 88 strains, confirming that the isolates were S. pneumoniae. Penicillin-binding protein 2B (PBP2B) class B region was positive in 32 strains, and PBP2B class A was in 2 strains. Twenty eight of 34 strains of PRSP contained the PBP2B class B gene. In the remaining six PRSP strains, neither the PBP2B class A nor B region was amplified. The PBP2B class B region was detected as a 180-kb fragment of SmaI digestion of S. pneumoniae DNA by Southern blot analysis, confirming that the detection of PBP2B class B gene by PCR is reliable. We concluded that the PBP2B class B gene is considered to be a major gene responsible for phenotypic resistance of PRSP. We performed genotyping by SmaI digestion pattern using pulsed field gel electrophoresis. No identical pattern was observed in isolates from inpatients, suggesting that apparent nosocomial infection of S. pneumoniae was negligible.

Aminoacyltransferases↗
PubMed1998

Sympathetic reinnervation demonstrated on serial iodine-123-metaiodobenzylguanidine SPECT images after cardiac transplantation.

The transplanted heart is without autonomic nervous control in the early postsurgical period. We present here a case of cardiac transplantation in which 123I-metaiodobenzylguanidine (MIBG) SPECT and an exercise-loading test were used to monitor the sympathetic reinnervation. The distribution of myocardial 123I-MIBG uptake extended with time from 1 to 2 yr after surgery. However, functional improvement, estimated by the heart rate response to exercise, was not discernable during this period. The findings in this case suggest the feasibility of 123I-MIBG SPECT imaging in the serial monitoring of sympathetic reinnervation after transplantation and that scintigraphic evidence of reinnervation precedes functional recovery.

3-Iodobenzylguanidine↗
PubMed1998

Fluorine-18-fluorodeoxyglucose PET identification of cardiac metastasis arising from uterine cervical carcinoma.

Cardiac metastasis of uterine cervical carcinoma is rare. We describe a patient with a past history of uterine cervical carcinoma who presented with metastasis to the heart, lungs and distant lymph nodes 3 yr after surgery and chemotherapy. Since the patient complained of chest pain and demonstrated electrocardiogram abnormalities, we performed echocardiography, electron beam CT and MRI, which revealed a tumor in the right ventricular wall. The tumor was assessed by 67Ga scintigraphy and 18F-fluorodeoxyglucose (FDG) PET scanning. The mean differential 18F-FDG uptake ratio of the tumor was 7.9, suggesting malignancy, which was later confirmed by myocardial biopsy. Information about the extent of the tumor and partial necrosis within it was provided by 18F-FDG PET. Although both radionuclide imaging techniques also detected metastatic lesions in the lungs and lymph nodes, 18F-FDG PET scanning detected small lesions more sensitively than 67Ga scintigraphy.

Adult↗
PubMed1997

G1 accumulation caused by iron deprivation with deferoxamine does not accompany change of pRB status in ML-1 cells.

We analyzed G1 accumulation induced by the iron chelator deferoxamine B mesylate (DFO) compared it with that caused by etoposide and cytosine arabinoside (AraC). The results showed that p53 protein increased with all three treatments without an increase in p53 mRNA. After treatment for 3 or 6 h, p21 mRNA increased with 10(-4) DFO to 159% or 556% of pretreatment levels, to 509% or 391% with 10(-5) etoposide, and to 263% or 304% with 10(-5) AraC. Induction of p21 protein was not observed with fluorescence activated cell sorting and Western blot analysis after treatment with DFO or AraC. Treatment with DFO did not cause any change in levels of CDK4 mRNA or protein, whereas etoposide or AraC treatment did diminish CDK4 protein. Enzyme linked immunosorbent assay for pRB and its phosphorylation, which reflects CDK4 activity, revealed that treatment with DFO did not change the amount of pRB or the phosphorylation status. Results of this investigation show that the mechanism of G1 accumulation induced by DFO involves a p53-independent pathway and that expression of p21 protein may be regulated posttranscriptionally.

Cell Division↗
PubMed1997

Evaluation of left ventricular ejection fraction from radial long-axis tomography: a new reconstruction algorithm for ECG-gated technetium-99m sestamibi SPECT.

UNLABELLED: Radial long-axis tomography can provide views similar to contrast left ventriculography (LVG) including the basal and apical areas of the left ventricle, not possible in routine short-axis tomography. We applied this method to ECG-gated Tc-99m Sestamibi (MIBI) myocardial SPECT images to estimate the left ventricular ejection fraction (LVEF). METHODS: ECG-gated Tc-99m MIBI SPECT was performed with a temporal resolution of 10 frames per R-R interval. LVEF was calculated on the basis of left ventricular volume estimates at end diastole (ED) and end systole (ES) with using an ellipsoid body model. To validate this method, LVEF's derived from ECG-gated Tc-99m MIBI SPECT were compared with those from LVG in 11 patients with coronary artery disease. RESULTS: There was a close linear correlation between LVEF values calculated from Tc-99m MIBI SPECT and those from LVG (r = 0.89, p < 0.001), although the gated SPECT underestimated LVEF compared to LVG. The technique showed excellent reproducibility (intra-observer variability, r = 0.96, p < 0.001; inter-observer variability, r = 0.71, p < 0.005). CONCLUSION: The radial long-axis tomography technique gives a good estimate of LVEF, in agreement with estimates based on LVG. ECG-gated Tc-99m MIBI SPECT can, therefore, be applicable to assess myocardial perfusion and ventricular function at the same time.

Adult↗
PubMed1997

Contribution of hypoxia to the development of cardiomyopathy in hamsters.

OBJECTIVE: It has been hypothesized that microvascular spasms cause cardiomyopathy. To elucidate the contribution of hypoxia to the development of cardiomyopathy, the newly-developed hypoxia tracer, Tc-99m nitroimidazole, was applied to detect myocardial hypoxia in a hamster model. METHODS: Tc-99m nitroimidazole (180 MBq) and I-125 iodoantipyrine (370 kBq) were injected into cardiomyopathic Syrian hamsters or control hamsters at age 10, 25, and 40 weeks (n = 6 in each group). The myocardial uptake of Tc-99m nitroimidazole was measured and dual tracer autoradiography was performed. RESULTS: Histologic study revealed that the cardiomyopathic hamsters at age 10, 25 and 40 weeks were in the myocytolytic stage, the fibrotic and healing stage, and the hypertrophy and dilatation stage, respectively. Tc-99m nitroimidazole uptake was significantly greater in the cardiomyopathic hamsters than in the controls at age 25 weeks (cardiomyopathic hamsters, 33.3 +/- 4.7% g dose/g; control, 25.2 +/- 3.1), whereas there were no significant differences between both strains at age 10 and 40 weeks. The quantified concentration of I-125 iodoantipyrine in the cardiomyopathic hamster at age 40 weeks was significantly lower than that in the controls. When the Tc-99m nitroimidazole uptake was normalized by I-125 iodoantipyrine concentrations, the cardiomyopathic hamsters at age 25 and 40 weeks showed significantly greater uptake than the controls. CONCLUSION: The myocardium in cardiomyopathic hamsters was hypoxic at the fibrotic and healing stage and may be hypoxic at the hypertrophy and dilatation stage. This may contribute to the development of cardiomyopathy.

Animals↗
PubMed1997

Reversibility of monocytic differentiation of HL-60 cells by 1alpha,25 dihydroxyvitamin D3.

Although 1alpha,25(OH)2D3 induces HL-60 cells to differentiate into monocytes, whether or not these monocytes revert to native promyelocytes is not clear. To investigate this question, HL-60 cells were treated with 1alpha,25(OH)2D3, and divided into CD14-positive and -negative cells with a cell sorter. These two populations were cultured with or without 1alpha,25(OH)2D3. Sorted CD14-positive HL-60 cells, treated with 1alpha,25(OH)2D3 for 7 days, reverted to CD14-negative cells and promyelocyte-like cells if 1alpha,25(OH)2D3 was removed from the medium. We conclude that the 1alpha,25(OH)2D3-induced differentiation of HL-60 cells into monocytes is reversible, and continuous administration of 1alpha,25(OH)2D3 is required for the differentiation of HL-60 cells.

Calcitriol↗
PubMed1997

Molecular analysis of the cyclin-dependent kinase inhibitor genes, p15, p16, p18 and p19 in the myelodysplastic syndromes.

The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal blood disorders characterized by dyshematopoiesis with a frequent evolution to acute leukemia. Chromosomal deletions rather than translocations are the predominant karyotypic abnormalities in MDS, suggesting a recessive mechanism in the pathogenesis of MDS, such as inactivation of tumor suppressor genes. A group of cyclin-dependent kinase inhibitors, p15 (INK4B), p16 (INK4A), p18 (INK4C) and p19 (INK4D), are candidate tumor suppressor genes. To determine whether genetic alterations of these genes play an important role in the development and/or progression of MDS, we examined 46 samples from MDS patients by Southern blotting, single-strand-conformation polymorphism (SSCP) using polymerase chain reaction (PCR) and sequencing of DNA. These samples included 13 refractory anemias (RA), four refractory anemias with ringed sideroblasts (RARS), 16 refractory anemias with an excess of blasts (RAEB), eight refractory anemias with an excess of blasts in transformation (RAEB-T) and five chronic myelomonocytic leukemia (CMMoL) samples. Except for allelic polymorphisms or silent point mutations, no alterations of coding regions of these four CDKI genes were identified. In summary, genetic abnormalities of the p15, p16, p18 and p19 genes are rare events in the development and/or progression of MDS.

Blotting, Southern↗
PubMed1997

Effect on an iron-chelator on ascorbate-induced cytotoxicity.

We investigated the effect of deferoxamine mesylate (DFO), an iron chelator, to test whether ascorbate-induced cytotoxicity is due to iron-catalyzed oxidation. Exposing human promyelocytic leukemic HL-60 cells to either sodium ascorbate or ascorbic acid for 1 h resulted in the progressive production of apoptotic cells characterized by cell shrinkage, as well as nuclear and internucleosomal DNA fragmentation. The addition of micromolar to millimolar concentrations of DFO during the 1-h exposure did not inhibit, but rather enhanced the ascorbate-induced apoptosis in both regular and serum-free RPMI1640 medium. However, a higher concentration of serum significantly inhibited the ascorbate-induced cytotoxicity. In contrast, the cytotoxic activity of ascorbate against T98G human glioblastoma cells was enhanced or reduced by micromolar and millimolar concentrations of DFO, respectively. Ascorbate significantly increased the oxidation potential in the culture medium, and the pro-oxidant action of ascorbate was further augmented by the presence of the cells. DFO did not significantly affect the ascorbyl radical intensity and only slightly reduced the ascorbate-elevated oxidation potential. These data demonstrated that ascorbate can induce cytotoxicity even in iron-deficient medium.

Apoptosis↗