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Hiroshi Fukuda

Publications and source records attributed to Hiroshi Fukuda.

At least 73 records · Page 4Linked to original sources
PubMed2003

Tumor detection using 18F-labeled matrix metalloproteinase-2 inhibitor.

Matrix metalloproteinase-2 (MMP-2) is a key enzyme involved in tumor invasiveness. (2R)-2- [4-(6-[(18)F]Fluorohex-1-ynyl)-benzenesulfonylamino]-3-methylbutyric acid ([(18)F]SAV03), a new fluorine-18 labeled MMP-2 inhibitor developed for tumor imaging with PET, was biologically evaluated using in vivo tumor model. Enzymatic MMP-2 assay of SAV03 yielded an IC(50) value of 1.9 microM. Biodistribution study of [(18)F]SAV03 using Ehrlich tumor bearing mice showed that the uptake in tumor was higher than in other organs, except for the liver, small intestine, and bone. When [(18)F]SAV03M, a methyl ester of [(18)F]SAV03, was used as a prodrug, the uptake in liver at 30 min after injection decreased by half and that in tumor increased by 2.4 times, compared with [(18)F]SAV03. Radio-thin-layer chromatographic analysis of [(18)F]SAV03M metabolites revealed that administered [(18)F]SAV03M was easily converted to the parent drug in vivo and accumulated in tumor tissue. Thus, [(18)F]SAV03M is suitable as the prodrug of [(18)F]SAV03 with potent efficacy. Whole body autoradiography using [(18)F]SAV03M also indicated tumor-specific accumulation of radioactivity, while higher accumulations in bone and intestinal contents were observed. Our results suggest that [(18)F]SAV03M could be potentially suitable for tumor imaging with PET.

Animals↗
PubMed2003

Thinking of the future and past: the roles of the frontal pole and the medial temporal lobes.

Human lesion data have indicated that the frontal polar area might be critically involved in having an insight into one's future. Retrospective memory mediated by medial temporal lobes and related structures, on the other hand, could be used to extract one's future prospects efficiently. In the present study, we investigated the roles of these two brain structures in thinking of the future and past by using positron emission tomography (PET) and a naturalistic task setting. We measured regional cerebral blood flow (rCBF) in healthy subjects while they were talking about their future prospects or past experiences, with regard to two different temporal windows (in years or days). Many areas in the frontal and the medial temporal lobes were activated during the future and past tasks compared with a control task requiring semantic retrieval. Among these, areas in anteromedial frontal pole showed greater activation during the future tasks than during the past tasks, showing significant effect of temporal distance from the present. Most areas in the medial temporal lobes showed greater or equivalent level of activations during the future tasks compared with the past tasks. The present results suggest that thinking of the future is closely related to retrospective memory, but that specific areas in the frontal pole and the medial temporal lobes are more involved with thinking of the future than that of the past.

Adult↗
PubMed2003

Context-dependent cortical activation in response to financial reward and penalty: an event-related fMRI study.

An event-related fMRI technique was used to assess neural responses to financial reward and penalty during a simple gambling task. We attempted to determine whether brain activities are dependent on the unique context of an event sequence. Thirty-six healthy volunteers participated in the study. The task was to guess the color of the suit of a card on each trial and to respond by pressing a button. Every correct response ("win") and incorrect response ("loss") was associated with financial reward and penalty, respectively. The magnitude of reward or penalty in each trial did not change; however, the subjects' self-reported emotional arousal was significantly higher for the events of "the fourth win of four wins in a row" and "the fourth loss of four losses in a row." We also found that the bilateral anterior cingulate and medial prefrontal cortices were specifically activated when the subjects experienced "the fourth win of four wins in a row" and "the fourth loss of four losses in a row." When the subjects experienced "a win following four losses in a row" or "a loss following four wins in a row," the right dorsolateral prefrontal cortex was specifically activated. Our data indicate that there exist brain activities associated with the event-sequence context in which abstract reward or penalty is received. These context-dependent activities appear to be crucial for adapting oneself to new circumstances and may account for clinical symptoms of various mental illnesses in which dysfunction of these regions has been reported.

Adolescent↗
PubMed2003

Specific p53 mutations predict poor prognosis in oral squamous cell carcinoma.

In this study, we focused on p53 mutations in specific regions, including DNA-binding surface regions, to clarify the correlation between mutations within the specific regions of p53 and clinical outcomes of patients with oral cancers. We analyzed p53 mutations in 121 fresh primary oral squamous cell carcinomas (SCCs) by polymerase chain reaction-single-strand conformation polymorphism or a yeast functional assay. p53 mutations were detected in 51/121 (42%) cases. Mutation of p53 was not associated with any clinicopathological parameters; however, tumors containing specific p53 mutations, e.g. DNA-binding surface regions (L2, L3 and the LSH motif) and conserved regions (II-V), had significantly poorer prognoses than tumors with mutations outside of those regions. Moreover, locoregional failure, lymph node metastasis and the occurrence of subsequent distant metastasis were also significantly associated with mutations within DNA-binding surface regions. These data indicate that specific mutations of p53 could be important prognostic factors in oral SCCs.

Aged↗
PubMed2003

Coronary flow reserve in patients with vasospastic angina: correlation between coronary flow reserve and age or duration of angina.

OBJECTIVES: This study sought to assess the coronary flow reserve (CFR) in patients with pure vasospastic angina (VSA). METHODS AND RESULTS: The phasic flow velocities of both spasm-positive and spasm-negative coronary arteries of the left anterior descending artery (LAD) were recorded at rest and during hyperaemia (50 microg of adenosine triphosphate infusion intracoronary) using a 0.014 inch, 15 MHz Doppler guide wire in 42 patients with pure VSA and acetylcholine (ACh)-induced coronary artery spasms (20-100 microg), and 23 controls with normal coronary arteries without ACh-induced vasospasm. These 42 patients had 16 vessels with focal spasms (>99%), 17 vessels with diffuse spasms (>90%) in the LAD, and nine vessels with ACh-induced spasms in the right coronary artery, but not the LAD. Coronary flow reserve was obtained from the ratio of the hyperaemic/baseline time-averaged peak velocity. Coronary flow reserve did not differ between patients with VSA and the controls (2.9+/-0.8 versus 3.2+/-0.7, NS). Moreover, CFR did not differ among the four cases (focal: 2.8+/-0.7; diffuse: 3.0+/-0.9; non spasm: 2.9+/-0.7 versus controls: 3.2+/-0.7, respectively, NS). Coronary flow reserve in vessels with proximal spasms was significantly higher than that in vessels with mid or distal spasms (3.4+/-0.8 versus 2.6+/-0.6, 2.6+/-0.9, p<0.05). The only significant correlation was between CFR and age (p=0.0275) or the duration of angina before admission (p=0.0405). CONCLUSIONS: There was no difference in CFR in patients with ACh-induced spasms between the spasm-positive and spasm-negative vessels. Moreover, CFR was maintained normally in vessels with diffuse spasms, as in those with focal spasms. The most important determinant factors for CFR in patients with VSA were age and the duration of angina before admission.

Age Factors↗
PubMed2003

Induction of coronary artery spasm by two pharmacological agents: comparison between intracoronary injection of acetylcholine and ergonovine.

BACKGROUND AND OBJECTIVES: There have been few studies comparing the clinical usefulness for the induction of coronary artery spasm (CAS) between acetylcholine (ACh) and ergonovine (ER). This study is designed: (1) to examine the duration of effect after intracoronary injection of ACh on the responsible vessels using a 0.014 inch, 15 MHz Doppler guide wire, and (2) to evaluate the efficacy of two pharmacological agents, ACh and ER, for the induction of CAS in patients with <50% stenosis in the cardiac laboratory. METHODS: Phasic coronary flow velocity patterns were recorded at rest and during ACh tests in 22 patients with normal or near-normal coronary arteries. The tip of the guide wire was placed on the proximal right coronary artery (RCA) and mid-left anterior descending artery. We measured the time required to baseline level of average peak velocity after intracoronary injection of ACh. We performed selective intracoronary administration of both ER and ACh in the same 171 patients (106 men, 65 women, mean age of 62+/-10 years) with <50% stenosis. Under no medication, ACh was injected first in incremental doses of 20, 50, and 80 microg into the RCA and of 20, 50, and 100 microg into the left coronary artery (LCA). Ten minutes later, ER was administered at 10 microg/min for four minutes for a maximal dose of 40 microg on the RCA and at 16 microg/min over four minutes for a total dose of 64 microg on the LCA. Positive spasm was defined as > or =99% luminal narrowing. RESULTS: The time-averaged peak velocity returned to baseline after intracoronary injection of ACh within 10 minutes in all 120 procedures, consisted of 19 with positive spasm (RCA (n=10): 245+/-33 s; LCA (n=9): 351+/-187 s) and 101 with negative spasm (RCA (n=48): 155+/-62 s, LCA (n=53): 248+/-106 s). In the overall results, there was no difference concerning the incidence of provoked spasm between the two pharmacological agents (ACh: 33% versus ER: 32%, NS). Coronary spasms were induced by either pharmacological agent in 134 vessels. Concordance in this study was 94% in all vessels, whereas the remaining 6% of vessels were different from each other. The non-concordance rate of the right coronary artery was significantly higher than that of the left coronary artery (10% versus 4%, p<0.01). However, ER provoked more focal spasms, whereas ACh provoked more diffuse and distal spasms, compared with each other. Seventy-four (55%) of the 134 vessels had coronary spasms in the same coronary arteries. Concordance of both provoked spasm sites and spasm configurations in the same coronary artery was observed in only 18 (13%) vessels. No serious or irreversible complications were observed during the two sequential tests. CONCLUSIONS: As a spasm provocation test, there were no differences between ACh and ER. We recommend the supplementary use of these two pharmacological agents for the induction of CAS in the cardiac laboratory, if available.

Acetylcholine↗
PubMed2003

Radioresistance in oral squamous cell carcinoma with p53 DNA contact mutation.

Reliable variables to predict the radiosensitivity of each tumor have not been identified. Recent studies have demonstrated that specific regions of mutations within the core domain of p53 protein correlate with responses to chemotherapy and radiotherapy in some tumor types. In this study, we evaluated the relationship between specific p53 mutations and radiosensitivity in 49 patients with oral squamous cell carcinomas (SCCs) who underwent preoperative radiotherapy. Exons 5 through 8 of the p53 gene were examined by polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. We detected p53 mutations in 27 (55.1%) cases. DNA contact mutations were detected in 11 (40.7%) of these 27 cases in L3 loop, loop-sheet-helix motif, and zinc-binding residues. Tumors containing p53 DNA contact mutations had significantly poorer responses to radiation than the other tumors, although no statistically significant difference between tumors with and without p53 mutations was found. These data indicate that DNA contact mutation of p53 could be a useful marker to predict the radioresistance of oral SCCs.

Adult↗
PubMed2003

Changes of biomechanical characteristics of the bone in experimental tibial osteotomy model in the dog.

Experimental osteotomy model of canine tibia was prepared to investigate the changes in biomechanical characteristics during the healing process. After 16 weeks, although radiographs revealed that fracture healing proceeded, the recovery rates of the mechanical parameters ranged from 12.3 to 47.3%, compared to the intact side. After 32 weeks, those recovered to 68.9-93.2%. These results suggested that the biomechanical characteristics of the healing bone could not be recovered sufficiently even after the passage of the healing period which has been empirically proposed from clinical findings. It was also considered that evaluation of the mechanical parameters using this osteotomy model would be suitable for investigating the effect of osteoinductive growth factors on fracture healing.

Animals↗
PubMed2003

Limitations of medical therapy in patients with pure coronary spastic angina.

OBJECTIVES: To assess the efficacy of medication for the treatment of pure coronary spastic angina, 71 consecutive patients with this diagnosis who had undergone coronary arteriography in a hospital with a follow-up of at least 2 years were studied. METHODS AND RESULTS: All 71 patients without significant organic stenosis were treated with long-acting calcium antagonists. The disappearance of chest pain attacks while receiving medical therapy was observed in 27 patients (38%), whereas the remaining 44 patients (62%) had chest pain attacks. Of special interest, 30 patients had more than one attack per month irrespective of the administration of calcium antagonists or isosorbide dinitrate. Medical treatment showed a good response in female patients (63% vs 31%, respectively; p < 0.05) and those with ST-segment elevation during selective spasm provocation tests (63% vs 30%, respectively; p < 0.05). In contrast, patients with a longer history of chest pain attacks before hospital admission and those with diffuse spasms (77% vs 34%, respectively; p < 0.01) had poor responses to medical treatment. In this study, neither sudden death nor acute myocardial infarction was observed during the follow-up periods. CONCLUSION: The limitations of medical therapy, including the administration of long-acting calcium antagonists, were observed in 30 of 71 patients (42%) with pure coronary spastic angina. Medical treatment was effective in only 38% of patients with pure coronary spastic angina in Japan.

Acetylcholine↗
PubMed2003

Did the widespread use of long-acting calcium antagonists decrease the occurrence of variant angina?

BACKGROUND: We have not often encountered variant angina (VA) since the use of long-acting calcium antagonists (L-CAs) became widespread. OBJECTIVES: This study examined the frequency of VA retrospectively. METHODS: and results: We diagnosed angiographically confirmed coronary spastic angina (CSA) in 349 consecutive patients using selective spasm provocation tests from January 1991 to December 2002. During this period, 3,148 diagnostic cardiac catheterizations and 1,515 selective spasm provocation tests were performed. Seventy-four of these 349 patients (21.2%) had VA. Coronary spasms were defined as transient luminal narrowings of > 99%, and VA was defined as an ST elevation during spontaneous attacks or noninvasive stress tests. We classified the 12 years of the study into four periods of 3 years each. No tendency to decrease for the ratio of the number of patients with CSA and the number of selective spasm provocation tests was observed among the four time periods (18%, 24%, 32%, and 23%, respectively). However, the number of patients with VA (28, 33, 9, and 4) and the VA/CSA ratio (32%, 28%, 14%, and 5%, respectively) in the four group significantly decreased. The frequency of administration of calcium antagonists (CAs) before hospital admission (49% vs 33%, respectively; p < 0.05) was significantly higher in the last time period (from 2000 to 2002) than in the first period (from 1991 to 1993). L-CAs were administered in > 90% of CSA patients who had been medicated with CAs before hospital admission in the last period (from 2000 to 2002), while L-CAs were administered in only 20% in the former period (from 1991 to 1993). The administration of statins and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers before hospital admission gradually increased according to the period passed, but not significantly. CONCLUSION: The frequency of VA has decreased in Japan, possibly due to the widespread use of therapy with L-CAs.

Angina Pectoris, Variant↗
PubMed2003

[Evaluation of brain in myotonic dystrophy using diffusion tensor MR imaging].

In many cases of myotonic dystrophy, high-intensity areas are seen in the cerebral white matter on T2-weighted imaging. Brain MRI was performed in 15 patients with myotonic dystrophy using diffusion tensor imaging, which is sensitive to the detailed structure of white matter, and the results were compared with those of normal controls. FA (anisotropic diffusion) values in the cerebral white matter of myotonic dystrophy patients were significantly lower than those of normal controls (p< 0.01), even if the hyperintense lesion was not seen on T2-weighted imaging. Values of trace (isotropic diffusion) in myotonic dystrophy patients were significantly higher than those of normal controls (p< 0.05), except in the posterior limb of the internal capsule. Diffusion tensor imaging could detect pathological change of the cerebral white matter in myotonic dystrophy patients, and may be useful for quantification and detection of subtle pathological change.

Adult↗
PubMed2003

Evaluation of 18F-FDG PET in patients with advanced, metastatic, or recurrent gastric cancer.

UNLABELLED: PET with 18F-FDG has been widely used in oncology, but its application for stomach neoplasms has been limited. The aim of this study was to evaluate the visual diagnostic accuracy of (18)F-FDG PET for advanced, metastatic, or recurrent gastric cancer and to generate semiquantitative values for lesions. METHODS: 18F-FDG PET scans were obtained on 42 patients (29 men, 13 women; age, 27-78 y; median age, 63 y): 20 patients with a PT931/04 scanner and 22 patients with a SET2400W scanner. The PT931/04 has a spatial resolution of 6.0 mm at full width at half maximum (FWHM) and covers 15 cm above and below the targeted lesion, and the SET2400W has a spatial resolution of 3.9 mm at FWHM and images the entire body. All PET images were interpreted visually, and tracer uptakes were quantitated as standardized uptake values (SUVs) on SET2400W images. RESULTS: The sensitivity, specificity, and accuracy as a whole were as follows: 71%, 74%, and 73%, respectively, with the SET2400W scanner and 47%, 79%, and 62%, respectively, with the PT931/04 scanner. Values were high for primary lesions, liver, lymph node, and lung metastases, but were low for bone metastases, ascites, peritonitis, and pleuritis carcinomatoses. SUVs were 8.9 +/- 4.2 (primary lesions, 19 patients/19 lesions), 6.5 +/- 2.2 (liver, 9/55), 6.1 +/- 2.5 (lymph nodes, 14/38), 6.5 +/- 1.8 (abdominal wall, 4/7), 3.9 +/- 2.0 (bone, 3/27), and 4.7 +/- 2.6 (lung, 2/3). Comparing SUVs and histologic findings for 17 untreated patients, values for well-differentiated and moderately differentiated adenocarcinomas versus poorly differentiated adenocarcinomas and signet ring cell carcinomas were 13.2 +/- 6.3 (4/4) versus 7.7 +/- 2.6 (13/13) (P < 0.05) for the primary lesions, 7.0 +/- 2.4 (5/39) versus 5.6 +/- 2.8 (2/2) for the liver, and 5.5 +/- 1.9 (9/28) versus 8.8 +/- 3.3 (3/8) (P < 0.05) for the lymph nodes. CONCLUSION: Our results indicate that 18F-FDG PET is a useful diagnostic modality for advanced, metastatic, or recurrent gastric cancer but not for detecting bone metastases, peritonitis, or pleuritis carcinomatoses. 18F-FDG uptake by gastric cancers is relatively high but does not parallel histopathologic features of malignancy.

Adult↗
PubMed2003

[A case of complete regression of metastatic renal cell carcinoma following corticosteroid treatment].

A 72-year-old man presented with hemosputum and was admitted to our hospital. Computed tomography and osseous scintigraphy revealed right renal cancer and multiple pulmonary and osseous metastases. A translumbar nephrectomy was performed. The histopathological examination demonstrated granular cell carcinoma and clear cell carcinoma. The patient complained of dyspnea on postoperative day (POD) 16, and chest X-ray showed progression of the multiple pulmonary metastases and lymphangitis carcinomatosa. Betamethasone was administered for palliative treatment. After the treatment, dyspnea improved and chest X-ray on POD 57 showed disappearance of the multiple pulmonary metastases and improvement of lymphangitis carcinomatosa. Computed tomography and osseous scintigraphy confirmed complete regression of metastases. He has been free from recurrence for 16 months after the nephrectomy and for 13 months after the complete regression. To our knowledge, this is the first case of complete regression of metastatic renal cell carcinoma following corticosteroid treatment reported in Japan, and the second case when foreign literature is included.

Aged↗
PubMed2002

Time-dependent contribution of the hippocampal complex when remembering the past: a PET study.

Previous studies of brain-damaged patients and functional neuro-imaging have consistently shown the importance of the hippocampal complex, i.e. the hippocampus and parahippocampal gyrus, in episodic memory retrieval. We wished to determine whether patterns of brain activation during memory retrieval as measured by PET are same or different when the oldness of a to-be-retrieved episode is manipulated. Using cue words, subjects remembered related episodes from three periods of their life, childhood, adolescence and recent period. The results showed an increase of parahippocampal activities during recall of episodes from childhood and recent period, but not from adolescence. These data suggest a possibility of time-dependent hippocampal contribution in episodic recall, which cannot be understood in simple terms of recent remote memory dichotomy.

Adolescent↗
PubMed2002

Neural basis of the retrieval of people's names: evidence from brain-damaged patients and fMRI.

The aim of this study was to identify the neuroanatomical basis of the retrieval of people's names. Lesion data showed that patients with language-dominant temporal lobectomy had impairments in their ability to retrieve familiar and newly learned people's names, whereas patients with language-nondominant temporal lobectomy had difficulty retrieving newly learned people's names. Functional magnetic resonance imaging experiments revealed activations in the left temporal polar region during the retrieval of familiar and newly learned people's names, and in the right superior temporal and bilateral prefrontal cortices during the retrieval of newly learned information from face cues. These data provide new evidence that the left anterior temporal region is crucial for the retrieval of people's names irrespective of their familiarity and that the right superior temporal and bilateral prefrontal areas are crucial for the process of associating newly learned people's faces and names.

Adolescent↗
PubMed2002

Use of multidetector row CT with volume renderings in right lobe living liver transplantation.

Multidetector row CT is a feasible diagnostic tool in pre- and postoperative liver partial transplantation. We can assess vascular anatomy and liver parenchyma as well as volumetry, which provide useful information for both donor selection and surgical planning. Disorders of the vascular and biliary systems are carefully observed in recipients. In addition, we evaluate liver regeneration of both the donor and the recipient by serial volumetry. We present how multidetector row CT with state-of-the-art three-dimensional volume renderings may be used in right lobe liver transplantation.

Blood Volume↗
PubMed2002

Spin probe study on the interaction of chitosan-derived polymer surfactants with lipid membrane.

Chitosan-derived polymer surfactants, sulfated N-acyl-chitosan (S-Cn-Chitosan), were synthesized and compared with commonly used low-molecular-weight surfactants, sodium dodecyl sulfate (SDS), dodecyltrimethyl ammonium chloride (DTAC), and octaethyleneglycol mono n-dodecyl ether (BL8SY), in their interaction with a lipid membrane using a spin probe method. A suspension of dipalmitoylphosphatidyl-choline (DPPC) spin-labeled strongly (10%) with a spin probe, 1-palmitoyl-2-(12-doxyl) stearoyl-phosphatidylcholine, was mixed with the surfactant solutions. The dissolution time of the DPPC membrane was estimated from the peak height change vs time, which was caused by the decrease in spin-exchange interaction. The times were 2, 4, and 70 s for BL8SY, SDS, and DTAC and 1.2 and 8.8 h for S-C10-Chitosan and S-C14-Chitosan, respectively, showing that the dissolution of the lipid membrane with polymer surfactants was far slower than that with low-molecular-weight surfactants. In addition, the time depended on the length of the alkyl chains of the polymer surfactants. Simulations of the ESR spectra of the DPPC-surfactant systems containing small amounts of surfactants were carried out in order to examine how the membrane structure was changed by the incorporation of surfactant molecules. By this analysis, it was revealed that the rigidity of the membrane was decreased by the addition of low-molecular-weight surfactants in the order of DTAC>SDS>BL8SY, inverse to the order of dissolution times. S-Cn-Chitosan, in contrast, increased the rigidity of the membrane, suggesting that polymer surfactants adhered to the lipid membrane and tightly enfolded the riposome anchoring their alkyl chains.

1,2-Dipalmitoylphosphatidylcholine↗