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Biomedical subjects

H Fukuda

Publications and source records attributed to H Fukuda.

At least 253 records · Page 14Linked to original sources
PubMed1999

Long-term follow-up results of adult patients with acute lymphocytic leukemia or lymphoblastic lymphoma treated with short-term, alternating non-cross-resistant chemotherapy: Japan Clinical Oncology Group Study 8702. Lymphoma Study Group.

BACKGROUND: Patients with acute lymphocytic leukemia (ALL) and those with lymphoblastic lymphoma (LBL) have overlapping clinical and immunophenotypic features and they have been treated with the same or very similar chemotherapy regimens. The goal of this multi-institutional phase II trial was to evaluate the therapeutic efficacy of a short-term, six-drug chemotherapy regimen for adult patients with untreated ALL or LBL. METHODS: Forty-six eligible patients, 41 with ALL and five with LBL, were treated with a short-term (planned total therapy duration; 36-38 weeks), simplified chemotherapy program; two courses of VEPA-L (vincristine, cyclophosphamide, prednisolone, doxorubicin, I-asparaginase plus intrathecal methotrexate and prednisolone) followed by four courses of M-VEPA (methotrexate plus VEPA), without the traditional maintenance therapy using daily 6-mercaptopurine and weekly methotrexate. RESULTS: Thirty-six (78%; 95% confidence interval 64-89%) of the 46 eligible patients achieved complete remission (CR). Among the 36 patients who achieved CR, four (11%) died of treatment complications, 26 (72%) relapsed and six (17%) remain alive in continuous CR. The median survival for all 46 eligible patients is 14 months and the median disease-free survival (DFS) for the 36 patients who achieved CR is 11 months. The estimate of the proportion of survival at 7 years of all 46 eligible patients is 15% at a median follow-up time of 96 months and that of DFS of the 36 patients achieving CR is 17% at a median follow-up time of 93 months. Subgroup analysis showed that an elevated serum C-reactive protein (CRP) level, age of 30 years or older, the presence of B-symptom and T-cell phenotype were likely to be associated with shortened survival. Although the observed CR rate (78%) is within the range of satisfaction, the long-term survival rate (15%) is inferior to those of published programs incorporating maintenance therapy. CONCLUSIONS: A fraction of adult patients with ALL or LBL are curable with a short-term, six-drug chemotherapy regimen. However, this simplified therapy of shorter duration cannot be recommended.

Adolescent↗
PubMed1999

Oral triacylglycerols regulate plasma glucagon-like peptide-1(7-36) and insulin levels in normal and especially in obese rats.

In a previous study of glucose tolerance, plasma insulin levels were greatly elevated in genetically obese Wistar fatty rats but not lean rats fed a diet containing polyunsaturated fatty acids. In the present study, triacylglycerol-regulation of levels of circulating insulin and glucagon-like peptide-1 (7-36) (GLP-1) has been investigated in these rats. In the glucose tolerance test, the two plasma insulin peaks appeared in obese and lean rats intubated with glucose + corn oil, at 15- 30 min and 4 h, whereas only the first peak appeared in rats intubated with glucose alone, although the glucose response did not differ. After intubation of corn oil only, the insulin peak at 15 min was not detected but the peak at 4h was large. The two plasma GLP-1 peaks appeared 15 min and 4 h after intubation of glucose + corn oil similarly to the insulin responses, although the first peak was small and the second peak was very large. A small peak at 15 min was not significant in rats intubated glucose alone and no peak was seen at 4 h. The GLP-1 concentrations were significantly higher in the following order: portal vein > inferior vena cava > tail vein. The plasma GLP-1 increment in response to oral triacylglycerols was significantly higher in obese rats than in lean rats as was the insulin increment. Thus, oral triacylglycerols (possibly polyunsaturated) appeared to act at the gut lumen to stimulate GLP-1 secretion, which may be responsible for the second (4 h) insulin peak.

Administration, Oral↗
PubMed1999

Purification, characterization, and sequence determination of phospholipase D secreted by Streptoverticillium cinnamoneum.

Phospholipase D (PLD), secreted into the culture medium of an actinomycete, Streptoverticillium cinnamoneum, has been purified to homogeneity and characterized. The Stv. cinnamoneum PLD efficiently catalyzes both the hydrolysis and transphosphatidylation of various phospholipids, including phosphatidylethanolamine (PE), phosphatidylcholine (PC), and phosphatidylserine (PS). However, the substrate specificity differs between the two reactions; PE serves as the most preferred substrate for the hydrolysis, but PC and PS are better substrates than PE for the transphosphatidylation. In addition, the transphosphatidylation but not the hydrolysis of PE and PC is markedly activated on the addition of metal ions, especially Al3+. Nucleotide and amino acid sequence determination of the Stv. cinnamoneum PLD revealed the presence of common structural motifs identified in all PLD sequences from various species.

Aluminum↗
PubMed1999

Regulation of ATP citrate-lyase gene expression in hepatocytes and adipocytes in normal and genetically obese rats.

Transcriptional regulation of ATP citrate-lyase (ACL, one of the lipogenic enzymes) gene by glucose/insulin, polyunsaturated fatty acid (PUFA), and leptin has been investigated in hepatocytes and adipocytes of obese Wistar fatty rats and their lean littermates. The sequence spanning nucleotides -64 to -41 of the ACL gene, which is responsive to glucose/insulin stimulation [Eur. J. Biochem. 247, 497-502, 1997], was linked to a reporter gene and transfected into rat hepatocytes or adipocytes. The chloramphenicol acetyltransferase (CAT) activities in the presence of glucose alone were similar in primary cultured cells from both obese and lean rats. In the presence of glucose/insulin, however, the CAT activities were markedly increased in the hepatocytes of lean rats, but were not significantly increased in those of obese rats. The stimulation by glucose/insulin was reduced in PUFA-treated cells of lean rats. The stimulation was also reduced in leptin-treated cells or ob gene expression vector-containing cells. However, PUFA- or leptin-treated cells from obese rats did not show a significant reduction in insulin stimulation. The same effects were observed at the endogenous mRNA and enzyme levels. Similar results were seen in adipocytes, although the stimulation and suppression levels were much smaller than in hepatocytes. The expression of endogenous insulin receptor in hepatocytes and adipocytes was reduced in the presence of leptin or PUFA. We previously found that insulin-binding capacities are also reduced in the presence of leptin or PUFA and are very low in obese rats in comparison with lean. Moreover, gel mobility shift assays using end-labeled ACL(-64/-41) revealed that nuclear factor(s) including Sp1 bind specifically to the sequence, and DNA-protein complex formation is reduced in the obese rats. Thus, the reductions in the insulin-stimulated ACL transcription may be ascribed in part to reductions in insulin binding to receptors and DNA-protein complex formation.

ATP Citrate (pro-S)-Lyase↗
PubMed1999

Inhibition of Na+,K+-ATPase by cisplatin and its recovery by 2-mercaptoethanol in human squamous cell carcinoma cells.

Na+,K+-ATPase (EC 3.6.1.37) is assumed to be involved in the transport of cisplatin [cis-diamminedichloroplatinum(II)] into cells and to act as a modulator of 5-fluorouracil (5-FU) in combination therapy of cisplatin and 5-FU. Whereas inhibition of Na+,K+-ATPase activity by cisplatin is expected to have effects on both anti-cancer therapy and nephrotoxicity, the inhibition mechanism remains to be elucidated. We studied the inhibition of Na+,K+-ATPase activity by cisplatin using an enzyme partially purified from Ca9-22 cells derived from a human squamous cell carcinoma of the gingiva. Cisplatin inhibited the Na+,K+-dependent ATP hydrolysis activity, and this inhibition depended on both the concentration of cisplatin and the preincubation time with cisplatin. The time-dependent inhibition was thought to be caused by a slow change of cisplatin from the inactive to the active form. We further tested the effect of cisplatin on the partial reactions of the enzyme, Na+-dependent ATP hydrolysis and K+-dependent pnitrophenylphosphate hydrolysis activities to determine which step in the reaction sequence of Na+,K+-ATPase was inhibited. Cisplatin inhibited both activities depending on its concentration and the preincubation time, whereas the Na+-dependent ATP hydrolysis activity was inhibited even at lower concentrations. Formation of a phosphointermediate of Na+,K+-ATPase was also inhibited by cisplatin depending on the concentration and preincubation time. Cisplatin (500 microM) and 8-fold higher concentration of 2-mercaptoethanol (2-ME; 4 mM) prevented inactivation of the enzyme by cisplatin, and the Na+,K+-ATPase activity inhibited by pretreatment with cisplatin was also recovered almost completely by 2-ME. These results suggest that the active form of cisplatin inhibits the Na+,K+-ATPase activity by inhibiting the formation of a phosphointermediate of the enzyme and that the inhibition by cisplatin is arrested by an addition of thiol group.

Antineoplastic Agents↗
PubMed1999

FDG PET evaluation of residual masses and regrowth of abdominal lymph node metastases from colon cancer compared with CT during chemotherapy.

Fluorine-18-2-deoxy-2-fluoro-D-glucose (F-18 FDG) PET may be more suitable for follow-up after cancer treatment than other morphologic approaches, because it reflects tumor viability. A patient with abdominal lymph node metastases from colon cancer was followed by CT and F-18 FDG PET during chemotherapy. F-18 FDG PET tumor images changed in accordance with the clinical progress, whereas CT findings were relatively unchanged. This case clearly shows the utility of F-18 FDG PET for follow-up during cancer chemotherapy.

Abdominal Neoplasms↗
PubMed1999

Sclerosing mediastinitis: findings on fluorine-18 fluorodeoxyglucose positron emission tomography.

Whole-body serial positron emission tomography scanning was done using fluorine-18 fluorodeoxyglucose (F-18 FDG) in a patient with a mediastinal mass. Uptake correlated well with the clinical symptoms and aggressiveness of the disease. Based on the F-18 FDG findings, a biopsy specimen was taken from the active region of the mass, which confirmed the diagnosis of sclerosing mediastinitis.

Biopsy↗
PubMed1999

Detection of CBF deficits in neuropsychiatric disorders by an expert system: a 99Tcm-HMPAO brain SPET study using automated image registration.

The aims of this study were to develop an objective method for assessing rCBF deficits using a statistical image analysis protocol and to validate its effective use in clinical practice. 99Tcm-HMPAO brain SPET images were acquired for 40 normal subjects, 10 patients with Alzheimer's disease and 10 patients with depression. Automated image registration was used to standardize the size and shape of the brain structures for all subjects. The images of the first 30 normal subjects were used to construct a normal database. The CBF images of the other 10 normal subjects and the 20 patients were compared voxel by voxel with the normal database to map CBF abnormalities by statistical evaluation. The results were compared with the clinical reports of CBF images. The expert system detected all rCBF deficits reported by the nuclear physicians. Some additional areas with special information, like atrophy and bilateral asymmetry, were also identified by the expert system. We conclude that this expert system can delineate CBF deficits with sufficiently high accuracy, differentiating normal from abnormal CBF images using voxel-based comparisons. The use of an expert system improves rCBF SPET image evaluation.

Aged↗
PubMed1999

Pharmacokinetics of 10B-p-boronophenylalanine in tumours, skin and blood of melanoma patients: a study of boron neutron capture therapy for malignant melanoma.

To optimize the neutron dose for boron neutron capture therapy (BNCT), the boron-10 (10B) concentration kinetics of 10B-p-boronophenylalanine (BPA) were analysed in 22 melanoma patients with primary or metastatic melanomas who received BPA and subsequently underwent BNCT or surgery. The blood concentration in nine patients receiving 179.7+/-14.9 mg/kg BPA increased with time during intravenous infusion, peaked at the end of administration and decreased thereafter. The peak values at the end of administration were 9.4 2.6 microg 10B/g blood, and half-lives for the initial and second components of the blood clearance were 2.8 and 9.2 h, respectively. Skin concentrations in the 10 patients varied from case to case; however, skin-to-blood ratios were relatively constant at 1.31+/-0.22 during the 6 h after the end of administration. Boron concentrations in the tumours resected from the seven patients who were operated on decreased in parallel to the blood values, the tumour-to-blood ratio being relatively constant at 3.40+/-0.83. The present analytical data of BPA pharmacokinetics support our previous approach for optimizing the timing of irradiation and setting the neutron flux large enough for tumour eradication but still tolerable for normal skin.

Adult↗
PubMed1999

Body temperature correlates with functional outcome and the lesion size of cerebral infarction.

INTRODUCTION: Experimental studies have demonstrated that mild hyperthermia exacerbates ischemia-induced neuronal injury. MATERIAL AND METHODS: We examined the relationship between body temperature and functional outcome in 183 patients suffering from cerebral infarction, and admitted within 24 h from the onset of stroke. Patients' functional capacities in daily life were evaluated by Rankin's score before the attack (RS0), on the day of admission (RS1), and 3 months after the onset of stroke (RS90). RESULTS: RS90 showed an independent correlation with RS0, RS1, age, infarct size and maximum body temperature recorded within the first 7 days from the onset of stroke by multivariate analysis. History of previous cerebrovascular accidents, atrial fibrillation, hemorrhagic transformation, infection, and a hypothalamic lesion showed significant associations with RS90 by the Mann-Whitney U-test, but not by multivariate analysis. Infarct size correlated with body temperature, atrial fibrillation, and hemorrhagic transformation. CONCLUSION: Body temperature correlated well with both functional outcome and infarct size in patients with an acute cerebral infarction.

Acute Disease↗
PubMed1999

Vascular risk factors for atherosclerotic lesions of the middle cerebral artery detected by magnetic resonance angiography (MRA).

OBJECTIVES: To examine the relationship between atherosclerotic lesions of the middle cerebral artery (MCA) detected on MRA and vascular risk factors. MATERIAL AND METHODS: We retrospectively assessed 279 patients (mean age, 69.0+/-11.3 years) who visited the Department of Neurology of Masuda Red Cross Hospital and underwent three-dimensional, time-of-flight MRA of the head between January 1996 and October 1998. Cases of cerebral embolism and internal carotid artery occlusion were excluded. Diagnoses were cerebral infarction (n = 152) and others (n = 127). We evaluated stenotic or occlusive lesions of the MCA (M1 portion), using MRA. Age, sex, history of hypertension, HbA1c, total cholesterol, fasting triglyceride, high density lipoprotein, lipoprotein(a), blood pressure, hematocrit, smoking and left ventricular hypertrophy (LVH) on ECG were included in the analysis. RESULTS: 36 patients (12.9%) had stenotic or occlusive lesions of the MCA on MRA. Univariate analysis showed that age, hypertension and HbA1c were significantly correlated with MCA lesions. Multiple logistic regression analysis showed that HbA C and hypertension were significant and independent predictors for MCA lesions. CONCLUSION: Hypertension and high serum HbAlc levels may contribute to the development of atherosclerotic lesions of the MCA in Japanese people.

Adolescent↗
PubMed1999

Associations between self-assessed masticatory disability and health of community-residing elderly people.

OBJECTIVE: To examine the relationship between the self-assessed masticatory disability and the health of community-residing older people. METHODS: Of 1473 randomly selected people aged 65 years and older living in Settsu, Osaka Prefecture, in October 1992, data on general health status, history of health management, psychosocial conditions, and dental conditions were obtained from 1405 people by interviews made during home visits. Follow-up for 54 months was completed for 1306 subjects (93.0%; 1072 living, 234 deceased). RESULTS: Being over 75 years of age, having poor general health and poor dental status, not using dental health checks, not using general health checks, not participating in social activities, not feeling that life is worth living (no "ikigai"), and feeling anxious about the future were univariately and significantly associated with self-assessed masticatory disability. Logistic regression analyses indicated that being older than 75 years, having poor general health and poor dental status, not using dental health checks, and not participating in social activities were independently associated with self-assessed masticatory disability. The Cox proportional hazards model showed that being male, over 75 years of age, and in poor general health, as well as not using general health checks, and not participating in social activities were independently associated with mortality. Self-assessed masticatory disability was univariately and significantly related to mortality, but by itself was not a significant risk factor for mortality, because of the potential influence of other variables. CONCLUSIONS: Certain health and psychosocial factors are closely associated with self-assessed masticatory disability among older people. Further investigations are needed to determine whether masticatory disability is a significant risk factor for mortality.

Aged↗
PubMed1999

Low prevalence of clinicopathologic and sialographic changes in salivary glands of men with Sjögren's syndrome.

Sjögren's syndrome (SS) is uncommon in men and there are few reports that describe their clinical features. In the present study, we investigated salivary gland manifestations in men with SS and compared the results with those in women patients. This study included 12 men and 117 women with SS, and the mean stimulated parotid flow rate in men (4.1 ml/5 min, n = 10) was higher than that of the women (3.1 ml/5 min, n = 101). The prevalence of SS-related sialographic findings, such as globular and punctate sialectasis, was significantly (P<0.05) lower in men (3/11) than in women (72/117). The prevalence of grade 4 cases on labial salivary gland biopsy was also significantly (P<0.01) lower in men (4/11) than in women (82/111). These results indicate a lower prevalence of SS-related clinicopathologic and sialographic changes in men with SS than in women with the same condition.

Arthritis, Rheumatoid↗
PubMed1999

High malignant transformation rate of widespread multiple oral leukoplakias.

OBJECTIVE: This study was undertaken in order to investigate clinicopathologic characteristics and malignant potential of widespread multiple oral leukoplakias. PATIENTS AND METHODS: The present study includes 12 patients with widespread multiple leukoplakias (widespread patients) and 99 with localized lesions (localized patients), and all patients were followed for more than 6 months with the mean follow-up period of 4 years. RESULTS: Gingiva and tongue were the major affected sites of leukoplakias in the localized patients, whereas gingiva and buccal mucosa were predominantly affected in the widespread patients. The rate of developing carcinoma was significantly (P < 0.02) higher in the widespread patients (3/12) than in the localized patients (5/99), although there was no significant difference in the rate of dysplastic lesions between these groups. CONCLUSION: These results indicate that the widespread leukoplakias have a higher potential for the development of carcinoma than do the localized lesions.

Adult↗
PubMed1999

Primary targets of fluoroquinolones in Streptococcus pneumoniae.

Mutants of wild-type Streptococcus pneumoniae IID553 with mutations in parC were obtained by selection with trovafloxacin, levofloxacin, norfloxacin, and ciprofloxacin. All of the parC mutants were cross-resistant to the selecting agents but were not resistant to gatifloxacin and sparfloxacin. On the other hand, gyrA mutants were isolated by selection with gatifloxacin and sparfloxacin. The gyrA mutants were cross-resistant to gatifloxacin and sparfloxacin but were not resistant to the other fluoroquinolones tested. These results suggest that in wild-type S. pneumoniae the primary target of trovafloxacin, levofloxacin, norfloxacin, and ciprofloxacin is topoisomerase IV, whereas the primary target of gatifloxacin and sparfloxacin is DNA gyrase.

Anti-Infective Agents↗
PubMed1999

Tc-99m HMPAO SPECT in the evaluation of Alzheimer's disease: correlation between neuropsychiatric evaluation and CBF images.

The purpose of this study was to evaluate the effects of various covariants on the distribution pattern of Tc-99m HMPAO in patients with Alzheimer's disease by correlation analysis. Twenty patients with Alzheimer's disease and 15 age matched normal subjects participated. Tc-99m HMPAO brain SPECT and x ray computed tomography (CT) were acquired for each subject. SPECT images were transformed to a standard size and shape by automated image registration (AIR) and were used for group comparison by means of SPM96. Voxel based covariance analysis was performed on standardised images taking the age of patients, severity of disease (clinical dementia rating scale, mini mental state examination, physical self maintenance scale), and atrophy indices as variables. There was significantly decreased regional cerebral blood flow (rCBF) in the frontal, parietal, and temporal regions in the patient group (p<0.001), more marked in those patients having severe dementia. Covariance analysis disclosed that aging and severity of disease have a pronounced effect on rCBF, especially that of the left parietal region.

Aged↗
PubMed1999

Small hepatocellular carcinoma: relationship of signal intensity to histopathologic findings and metal content of the tumor and surrounding hepatic parenchyma.

PURPOSE: To investigate the relationship between the metal content of hepatocellular carcinoma (HCC) and the signal intensity pattern on magnetic resonance images. MATERIALS AND METHODS: The signal intensity patterns of 59 HCCs 3 cm in diameter or smaller were correlated with histologic findings and metal content. RESULTS: HCCs with high signal intensity on T1-weighted images demonstrated more steatosis (P = .035) and higher copper content (P = .008) than did surrounding hepatic parenchyma. HCCs with high signal intensity on T2-weighted images demonstrated more clear cells (P = .001) than did surrounding hepatic parenchyma. The higher signal intensities on T1-weighted and T2-weighted images were related to a higher and a lower degree of histologic differentiation, respectively. Multivariate analysis showed that the contrast-to-noise ratio between the HCC and surrounding hepatic parenchyma was affected by intratumoral copper content (P = .0338), zinc content of surrounding hepatic parenchyma (P = .0379), and the degree of histologic differentiation on T1-weighted (P = .0031) and T2-weighted (P = .0062) images. CONCLUSION: The signal intensity of HCC on T1-weighted images is related to the degree of histologic differentiation, intratumoral copper content, and zinc content of surrounding hepatic parenchyma, whereas the signal intensity on T2-weighted images is related to the degree of histologic differentiation.

Adult↗