Biomedical subjects

K Fukuchi

Publications and source records attributed to K Fukuchi.

At least 91 records · Page 5Linked to original sources

PubMed1997

Presence of Epstein-Barr virus genome in the bone marrow of patients with hematopoietic malignancies.

The Epstein-Barr virus (EBV) genome was detected by polymerase chain reaction (PCR) in mononuclear cells from bone marrows with diverse types of hematopoietic malignancies. Viral repeated sequences (BamHI-W region) were detected in 42 of 82 (51%) hematopoietic malignancies, including polycythemia vera, but not in nonneoplastic cases. EBV-positive cases were found to consist of various histological types. We did not detect any EBV PCR product in the peripheral blood. The EBV BamHI-Y, -H region, encoding EBV nuclear antigen 2 DNA, which is a single-copy gene in the viral genome, was detected in only 13 of 42 BamHI-W-positive cases, suggesting that the copy number of the EBV genome differed in each case. In all cases, the PCR band was verified by Southern blot hybridization using specific EBV probes. Whether the infected virus is an etiologic agent of the malignancy or merely a latent infection cannot be determined by the PCR assay performed under these conditions. These results, however, suggest that a novel form of EBV latent infection is present in the bone marrow of patients with hematopoietic malignancies.

Adult↗

PubMed1997

Myocardial iodine-123-metaiodobenzylguanidine images and autonomic nerve activity in normal subjects.

UNLABELLED: We studied the relationship between myocardial [123I]metaiodobenzylguanidine (MIBG) uptake and autonomic nerve activity in normal subjects. METHODS: MIBG scintigraphy and power spectral analysis (PSA) of heart rate variability were performed simultaneously in 15 normal subjects. Anterior planar images and SPECT images were taken at five and two points after the injection of [123I]MIBG, respectively. In 10 of 15 subjects, 201TI myocardial SPECT was performed immediately after MIBG scintigraphy. RESULTS: The heart/upper mediastinum MIBG uptake ratio in the planar image obtained at 240 min (r = 0.64, p < 0.01) and the washout rate of MIBG in the heart between 15 min and 240 min (r = 0.51, p < 0.05) showed significant correlation with the percentage of low frequency component of PSA (percent LF), an index of sympathetic nerve activity. Regional MIBG uptake in the inferior wall normalized by individual maximal uptake among all pixels was significantly correlated with the high frequency component of PSA, an index of parasympathetic nerve activity (r = -0.58, p < 0.05) and with mean R-R interval in a resting ECG (r = -0.82, p < 0.001) but did not correlate with percent LF, percent uptake of 201TI in the inferior wall or the liver/heart uptake ratio. CONCLUSION: These results indicate that myocardial MIBG uptake correlates with sympathetic nerve activity in normal subjects. Our data indicate that heterogeneous MIBG distribution in the left ventricle is a physiologic rather than artifactual phenomenon and may be related to vagal tone rather than sympathetic nerve activity.

3-Iodobenzylguanidine↗

PubMed1997

Comparison of iodine-123-iomazenil SPECT and technetium-99m-HMPAO-SPECT in Alzheimer's disease.

UNLABELLED: This study was designed to elucidate a central type of benzodiazepine (Bz) receptor distribution in patients with Alzheimer's disease using SPECT with [123I]iomazenil (IMZ). METHODS: Eight patients with probable Alzheimer's disease were studied. Benzodiazepine receptor imaging was performed 15 min (early) and 180 min (delayed) after intravenous administration of 167 MBq IMZ, sequentially, using hexamethylpropylene amine oxime (HMPAO) SPECT to evaluate regional cerebral perfusion. RESULTS: Early IMZ-SPECT depicted areas of reduced uptake in sites of decreased cerebral blood flow (CBF), but each area of decreased uptake was extended wider than the area of hypoperfusion. Delayed IMZ-SPECT images demonstrated a similar pattern of decreased area of CBF; the affected region in Bz receptor bindings, however, was clearer and broader compared with that in either HMPAO-SPECT or early IMZ-SPECT. In comparison with the uptakes for the normal cerebral hemisphere (ratio to the contralateral cerebellum) in patients with unilateral cerebral infarction as a control group (n = 4), the patients with Alzheimer's disease showed distinctive bilateral frontal or parietal defects (p < 0.05). CONCLUSION: Brain SPECT using IMZ may be more sensitive than CBF images in patients with Alzheimer's disease.

Alzheimer Disease↗

PubMed1997

Quantification of systolic count increase in technetium-99m-MIBI gated myocardial SPECT.

UNLABELLED: This study was performed to clarify the validity of quantification of myocardial wall thickening by the count increase method using electrocardiography (ECG)-gated SPECT. METHODS: We performed a phantom study to examine the quantification of this method and to clarify the relationship between the changes of relative counts and objective size (such as myocardial wall) under various conditions. In addition, in volunteers, the percent count increase (%CI) was analyzed in left ventricular segments based on circumferential profile curve analysis by ECG-gated SPECT with 99mTc-MIBI (methoxyisobutyl-isonitrile), and it was compared with the regional systolic wall thickness (%Th) assessed by echocardiography during low-dose dobutamine infusion. RESULTS: In our phantom study, the relative count changes were correlated linearly with the object size only within less than 20 mm. Recovery coefficient curves were influenced by acquisition parameters such as type of collimator, diameter of camera rotation, counts and photon scattering. In ECG-gated SPECT, the %CI value was increased gradually at each stage after dobutamine infusion, in relation to the increase of the %Th seen on echocardiography, although there are significant large deviations between these two parameters. CONCLUSIONS: In this study, quantitative analysis based on the %CI in ECG-gated SPECT may underestimate regional wall thickening. These data should be considered in the evaluation of the %CI as an index of myocardial function.

Adult↗

PubMed1997

[Analysis of genome-type, serovar and antibiotic susceptibility of Pseudomonas aeruginosa isolated in Beijing Hospital China in 1991 to 1993].

We analyzed the in vitro antibiotic susceptibility pattern and serovar for 192 strains of Pseudomonas aeruginosa isolated at Beijing Hospital(China) from October 1991 to October 1993. The frequency of resistant strains was high, more than 15%, for ceftazidime, cefsulodin, cefoperazone, aztreonam, gentamicin, tobramycin, tosufloxacin, ofloxacin and fosfomycin. The incidence of resistants against piperacillin and imipenem was significantly low. Among the 192 strains, 16 were designated as being multi-drug resistant strains(i.e.; resistant to more than 8 drugs out of 11 drugs), and all of the multi-drug resistant strains were isolated from inpatients. Predominant serovar of 192 strains were 60(31.3%) for G, 28(14.7%) for E, and 24(12.5%) for I. Multi-drug resistant strains have no characteristic serovar. Restriction enzyme SpeI digestion analysis(using pulse field electrophoresis) of P. aeruginosa-genome yielded several common patterns, and was shown to be useful for tracing the route of nosocomial infection. Further, isolates with closely related genome type, in which the size of one digested band was different, showed a different minimum inhibitory concentration of fosfomycin in one genome type or new quinolones in the other genome type. Analysis of genome type and antibiotic susceptibility pattern may exhibit the antibiotic resistant gene.

Anti-Bacterial Agents↗

PubMed1997

[Evaluation of the automatic quantification of left ventricular function using ECG gated 99mTc-MIBI myocardial SPECT].

We studied the accuracy of left ventricular (LV) volumes and ejection fraction (EF) derived from ECG gated 99mTc-sestamibi myocardial perfusion SPECT (G-SPECT) and the software for automatic data analysis (QGS program described by Germano G et al.). G-SPECT was performed in 29 patients with various cardiac diseases. LV end-diastolic and end-systolic volumes (LVEDV and LVESV), and LVEF determined by QGS program were compared to those by Simpson method in biplane left ventriculography (LVG). Interobserver reproducibility in measuring the G-SPECT parameters was excellent (LVEDV: r = 0.99, LVESV: r = 0.99, LVEF: r = 0.97). There was a good correlation between the values obtained from G-SPECT and LVG (LVEDV: r = 0.92, LVESV: r = 0.94, LVEF: r = 0.85), but G-SPECT tended to underestimate LVEDV and LVEF. In 17 patients with moderate to severe myocardial perfusion defects selected from the subjects, the correlation was maintained fairly high (LVEDV: r = 0.90, LVESV: r = 0.92, LVEF: r = 0.77). In conclusion, QGS program provides high accuracy and reproducibility in determining LV volumes and LVEF from G-SPECT.

Adult↗

PubMed1996

Expression of apolipoprotein E inhibits aggregation of the C-terminal fragments of beta-amyloid precursor protein.

An important role of apolipoprotein E in the amyloidogenesis of Alzheimer's disease is suggested by an accumulation of apolipoprotein E in beta-amyloid plaques and a genetic association between Alzheimer's disease and one of the allelic variants (APOE4) of apolipoprotein E. Overexpression of a C-terminal region of beta-amyloid precursor protein brings about aggregation of the C-terminal fragments in COS cells. This COS cell culture system was used to study effects of apolipoprotein E on aggregation of the C-terminal fragments. When both apolipoprotein E and the C-terminal fragments were overexpressed in COS cells, Western blot analyses revealed significant inhibition of aggregation of the C-terminal fragments. No significant differences between apolipoprotein E3 and E4 in the inhibitory activities were found by this method. Apolipoprotein E may inhibit formation of amyloid fibrils.

Alzheimer Disease↗

PubMed1996

Apoptosis of T cells in multicentric Castleman's disease.

Profound immunodeficiency in multicentric Castleman's disease has already been elucidated. In the present study, we investigated CD45RO and Fas antigen expression and apoptosis by T cells in three patients with this disease. T cell expression of CD45RO and Fas antigen was increased in two of the three patients, indicating in vivo lymphocyte activation. Apoptosis of T cells from the two patients with increased CD45RO and Fas antigen expression occurred after overnight culture in the presence of pokeweed mitogen. Occurrence of apoptosis was indicated by DNA laddering and nuclear chromatin condensation. Peripheral blood mononuclear cells from the two MCD patients revealed spontaneous apoptosis following 3 days of culture by quantitative assay using flow cytometry. These findings show that T cells are activated in some patients with multicentric Castleman's disease and suggest that this activation may promote apoptosis.

Apoptosis↗

PubMed1996

Natural killer (NK) lymphocytosis induced by Epstein-Barr virus (EBV) reactivation in monoclonal gammopathy of undetermined significance (MGUS).

We investigated the relationship between NK lymphocytosis and EBV infection in MGUS. We found that two out of 10 patients showed an increase of NK cells compared with normal controls In addition, these two patients had far higher levels of CD5LOW+ NK cells (activated NK cells) than controls. EBV DNA was detected by polymerase chain reaction in peripheral blood mononuclear cells from the two patients, although the other eight patients with MGUS and all 20 normal controls had no detectable EBV DNA. Furthermore, EBV DNA was detected in sorted CD5LOW+ NK cells. These results suggest that reactivation of EBV might be related to the increase of NK cells, particularly CD5LOW+ NK cells in some patients with MGUS.

Adult↗

PubMed1996

Heat shock-enhanced T cell apoptosis with heat shock protein 70 on T cell surface in multicentric Castleman's disease.

We report here that T cells from patients with multicentric Castleman's disease (MCD) are sensitive to hyperthermia. T cells from two of three patients with MCD revealed DNA ladder formation and chromatin condensation following heat shock (30 min at 41.5 degrees C). Peripheral blood mononuclear cells (PBMC) from the same MCD patients exhibited high levels of spontaneous apoptosis after 72 h in culture and elevated apoptosis after heat shock, as evaluated by a quantitative flow cytometric assay. Heat shock protein 70 (hsp70) was detected on the cell surface of T cells in all three patients after heat shock. Furthermore, hsp70 was detected on T cells in the two MCD patients with apoptosis even in the absence of heat shock. T cells from normal samples did not show either heat-shock-induced expression of cell-surface hsp70 or apoptosis. Thus, heat shock treatment augmented hsp70 expression on the cell surface of T cells and enhanced apoptosis. Our studies suggest that hyperthermia may influence the clinical course of MCD.

Antigens, Surface↗

PubMed1996

Overexpressions of cDNAs for beta-amyloid precursor proteins 695, 751, and 770 enhance the secretion of beta-amyloid precursor protein derivatives and the survival of P19-derived neurons.

P19 is a C3H mouse-derived line of multipotent embryonic carcinoma cells that differentiate into neural cells. P19 cell clones overexpressing the three major forms of beta-amyloid precursor protein from their cDNA constructs were established. Unlike a previous study in which P19-derived neurons had a limited alpha-secretase activity, all of these clones produced significant amounts of secreted beta-amyloid precursor protein. When treated with retinoic acid, these transformed lines differentiated into neurons and survived better than did nontransformed parental P19 cells. Furthermore, P19-derived neurons survived better in medium conditioned by the transformed P19 line, and survival was reduced by immunoabsorption with an antibody to beta-amyloid precursor protein. These results suggest neurotrophic effects of secreted beta-amyloid precursor protein and contrast with a previous report in which overexpression of a full-length cDNA for beta-amyloid precursor protein led to degeneration of P19-derived neurons. Western blot analysis suggested that this difference might result from different levels of expression of putative neurotoxic C-terminal fragments of beta-amyloid precursor protein; moreover, P19-derived neurons differ from P19 stem cells in the processing of these C-terminal fragments.

Amyloid beta-Protein Precursor↗

PubMed1996

cDNA cloning and chromosome mapping of the human Fe65 gene: interaction of the conserved cytoplasmic domains of the human beta-amyloid precursor protein and its homologues with the mouse Fe65 protein.

Using the yeast two hybrid system, a mouse embryo cDNA library was screened for proteins that interact with the C-terminus of the human beta-amyloid precursor protein (beta PP). A fusion protein was identified that interacts specifically with the cytoplasmic domain of beta PP and does not interact with the beta-amyloid region. The protein encoded by this partial mouse cDNA is identical to the C-terminus of the rat Fe65 protein. This mouse protein also interacts with the homologous C-terminal domains of the mouse amyloid precursor-like proteins, APLP1 and APLP2. These conserved cytoplasmic regions contain a common amino acid motif, Asn-Pro-Thr-Tyr, which has previously been shown to influence both the secretion and internalization of beta PP. Fe65 has been implicated in regulatory and cell signaling mechanisms because it contains two different motifs involved in protein binding, a WW domain (a variant of Src homology 3 domains) and a phosphotyrosine interaction domain (PID). Interestingly, the PID domain binds to the same motif present in the conserved cytoplasmic domains of the beta PP and beta PP-like proteins. RNA analyses reveal that Fe65 is predominantly expressed in brain and in the regions most affected by Alzheimer's disease (AD)-associated neuropathology. The human Fe65 mRNA was cloned from a fetal brain cDNA library. The message encodes a protein of 735 amino acids that is 95% identical to the rat Fe65 protein. The human Fe65 gene was mapped on human metaphase chromosomes to band 11p15 using fluorescence in situ hybridization.

Amino Acid Sequence↗

PubMed1996

High levels of circulating beta-amyloid peptide do not cause cerebral beta-amyloidosis in transgenic mice.

We have established transgenic mice that constitutively overproduce the signal sequence and the 99-amino-acid carboxyl-terminal region of the human beta-amyloid precursor protein. The transgenic mice strongly expressed the transgene in multiple tissues under the control of a cytomegalovirus enhancer/chick beta-actin promoter. There were exceptionally high levels of beta-amyloid peptides in the plasma (approximately 17 times or more compared with the human plasma level). Although some transgenic mice from one founder line developed amyloidosis in the intestine, no neuropathology was found in transgenic mice up to age 29 months. Given the absence of cerebral beta-amyloidosis despite extremely high levels of circulating beta-amyloid peptides in the transgenic mice, the results suggest that local cerebral metabolism of beta-amyloid precursor protein may play a predominant role in cerebral beta-amyloidosis in transgenic mice. Such transgenic mice may be useful for the investigation of the etiology of the disease and for the establishment of therapeutic strategies.

Amyloid beta-Peptides↗

PubMed1996

[Evaluation of 123I-iomazenil SPECT in patients with ischemic cerebrovascular disease: comparative study with 123I-IMP SPECT].

Clinical evaluation of 123I-iomazenil, a new imaging agent for central-type benzodiazepine receptors with SPECT, was performed in patients with ischemic cerebrovascular disease. We investigated 15 patients with angiographically-proven severe occlusive lesions (occlusion or > 70% stenosis) in the unilateral carotid system. 123I-iomazenil SPECT images were compared with cerebral blood flow (CBF) images and the cerebral perfusion reserve, which were measured using the "split dose 123I-IMP SPECT method" before and after the intravenous injection of 1 g of acetazolamide. For the detection of ischemic lesions, CBF images were superior to 123I-iomazenil images based on visual analysis. Regarding the count ratio of the affected MCA territory to the non-affected (L/N), 123I-IMP was lower than 123I-iomazenil in most of the cases. In five patients showing "crossed cerebellar diaschisis" by 123I-IMP, asymmetry of the cerebellar accumulation was observed in only one patient with 123I-iomazenil, which was less prominent than with 123I-IMP. There was no significant correlation between the L/N ratio with 123I-iomazenil and the cerebral perfusion reserve in the affected MCA territory. However, in some cases showing a decreased L/N ratio (< 90%) with 123I-iomazenil, a decreased CBF with normal perfusion reserve and cerebral hemi-atrophy were observed with 123I-IMP and MRI, which suggested the influence of neuronal loss due to chronic ischemia. These results indicate that 123I-iomazenil SPECT, which provides new information regarding neuronal loss due to ischemic damage to the brain, is useful for the evaluation of ischemic cerebrovascular disease.

Adult↗

PubMed1996

[Analysis of cyclin dependent kinase inhibitors, p16INK4a and p15INK4b gene, in acute lymphoblastic leukemias].

We examined the abnormality of p16INK4a and p15INK4b genes in 14 cases of human acute lymphoblastic leukemias (L1; 8 sample from 6 cases, L2; 10 samples from 7 cases, L3; 1 sample from 1 case) using DNA from bone marrow cells. The frequency of homozygous deletion of p16INK4a was 21.4% (3/14) and that of p15INK4b was 7.1% (1/14) and both genes were deleted in 7.1% (1/14) according to Southern blot and PCR analysis. The deletion of p16INK4a and/or p15INK4b was detected in 50% (3/6) of L1, 28.6% (2/7) of L2. The frequency of deletion was 33.3% (3/9) of B cell origin, 66.7% (2/3) of T cell origin and 0% (0/2) of nonBnonT cell origin. By PCR-SSCP analysis on exon 1 and exon 2 of p16INK4a and p15INK4b genes, we detected one case of unusual migrated band in L1 B cell origin. The base substitution, C to G, located in intron 1 of p15INK4b, 9 base upstream of intron 1-exon 2 boundary, was determined by DNA sequencing analysis. Deletion of p16INK4a and/or p15INK4b gene may contribute to etiology of ALL.

Adolescent↗

PubMed1996

[Multi-drug resistance of serovar E strains in clinically isolated Pseudomonas aeruginosa and analysis of genome pattern].

We analyzed the in vitro antibiotic susceptible pattern and serovar for 132 strains of pseudomonas aeruginosa (98 from inpatients and 34 from outpatients) isolated at Showa University hospital from September to December of 1993. The ratio of resistant strains was 38.6% for carbenicillin, 12.1% for piperacillin, 12.9% for ceftazidime, 12.1% for cefsulodin, 17.4% for cefoperazone, 9.1% for cefclidin, 24.2% for cefpirome, 7.6% for imipenem, 17.4% for amikacin, 16.7% for aztreonam, 89.4% for minocycline and 33.3% for ofloxacin. The incidence of resistance against minocycline, carbenicillin, ofloxacin was markedly high. Among the 132 tested strains of Pseudomonas aeruginosa, 16 were multi-drug resistant strains (i.e., resistant to more than 8 drugs out of 12 drugs), and 14 of the multi-drug resistant strains (87.5%) were isolated from inpatients. Multi-drug resistant strains were isolated most frequently from urine specimens. The antibiotics that remained effective against the multi-drug resistant strains included amikacin, imipenem, cefclidin and cefsulodin. The serovar of 116 strains (resistant to up to 7 drugs) was 27 for G, 24 for B, and 19 for E, and 15 of the 16 multi-drug resistant strains showed serovar E. Restriction enzyme SpeI digestion analysis (using pulse field electrophoresis) of P. aeruginosa having serovar E revealed common 650kb and 540kb bands in multi-drug resistant strains. The genome pattern was quoted for serovar E strain according to the restriction enzyme digestion pattern and was shown to be useful for tracing the route of infection.

Drug Resistance, Microbial↗

PubMed1996

Abnormal iodine-123-MIBG images in healthy volunteers.

We have encountered two healthy volunteers with significant reductions of myocardial [123I]MIBG (metaiodobenzylguanidine) uptake and rapid clearance. In one of these subjects (a 31-yr-old man), we performed additional examinations to clarify the mechanism of the abnormal myocardial MIBG uptake. There was no abnormality on orthostatic test, maximal exercise test (bicycle ergometer) or in plasma norepinephrine concentration. Nevertheless, power spectral analysis (PSA) of heart rate variability revealed that the percent low frequency component (%LF), an index of sympathetic nerve activity, was increased. Furthermore, [123I]MIBG scintigraphy after oral administration of an alpha 2 agonist (guanabenz acetate; 4 mg) demonstrated that myocardial uptake and clearance of MIBG returned to normal, as did the %LF. These results suggest that reduced uptake and rapid clearance of myocardial MIBG in this subject was strongly related to the increased release of norepinephrine from sympathetic nerve terminals due to augmented sympathetic activity. This subject illustrated that unsuspected, subclinical variants of normal or abnormal sympathetic functions may pose a diagnostic pitfall in interpretating myocardial MIBG images.

3-Iodobenzylguanidine↗

PubMed1996

Ischemic and reperfused myocardium detected with technetium-99m-nitroimidazole.

UNLABELLED: To evaluate the utility of 99mTc-labeled nitroimidazole (BMS) in the detection of ischemic or reperfused myocardium, we performed dual-tracer autoradiography with BMS and [125I]iodoantipyrine (IAP). METHODS: In open-chest rats, the left coronary artery was ligated to produce 15- or 60-min ischemia followed by reperfusion or 60-min ischemia without reperfusion. BMS was injected just before ligation, 1 min before reperfusion or 15 min after reperfusion. RESULTS: In the area at risk, regional myocardial blood flow (rMBF) evaluated by IAP recovered to the level in the nonischemic septum in all hearts, except in 60-min occlusion without reperfusion. In myocardium reperfused after 15-min ischemia (stunned), normalized BMS uptake (%BMS) in the area at risk was significantly increased only when BMS was injected before ischemia. When BMS was injected before 60-min ischemia or just before reperfusion, %BMS was significantly higher at the marginal zone of infarction than in the infarcted area. In contrast, %BMS was significantly lower in the infarcted area when BMS was injected during reperfusion. After 60 min of occlusion without reperfusion (permanent occlusion), rMBF in the area at risk was significantly decreased as was %BMS. In the peripheral zone of the area at risk, rMBF was significantly reduced, but %BMS was significantly increased. CONCLUSION: BMS images stunned myocardium only when it is injected before ischemia, while it images the area at risk subjected to prolonged ischemia when it is injected up to the time of reperfusion. The infarcted area can be negatively visualized when BMS is injected after reperfusion.

Animals↗