Biomedical subjects

H Fukuda

Publications and source records attributed to H Fukuda.

At least 433 records · Page 24Linked to original sources

PubMed1996

Prognostic significance of Ki67 (MIB1) proliferation index and p53 over-expression in chondrosarcomas.

To investigate the prognostic significance of the Ki67 (MIBI)-proliferation index and p53 over-expression in chondrosarcomas, we retrospectively analyzed a cohort of 29 patients with chondrosarcomas using immunohistochemical assays with MIBI and p53 monoclonal antibodies on formalin-fixed, paraffinembedded tissue samples with microwave preparation. We also assessed 19 patients with benign cartilaginous tumors as a control group. There was a significant positive correlation between MIBI index and tumor grade in chondrosarcomas, while there was no significant difference in the MIBI index between the grade-1 chondrosarcomas and the benign cartilaginous tumors. Patients categorized in the high-MIBI-index group had a significantly lower survival rate than those in the low-index group. Moreover, in analyzing the sub-set of the patients with grade-II chondrosarcomas, it was found that they could be prognostically sub-divided according to MIBI index. The p53 index also significantly correlated with patient survival, and there was significant correlation between the MIBI index and the p53 index. However, in multivariate analysis, only the MIBI index and tumor grade proved to be independent prognostic indicators of chondrosarcomas. These results demonstrate that the MIBI index can be a useful procedure for assessing tumor grade in chondrosarcomas, especially for determining the prognosis of patients with grade-II chondrosarcoma.

Adolescent↗

PubMed1996

Mutations in the p53 gene and human papillomavirus infection as significant prognostic factors in squamous cell carcinomas of the oral cavity.

The p53 gene has been indicated to be a tumour suppressor gene that is found in mutated form in common human cancers. Human papillomavirus (HPV) has oncogenic activity in cervical and oral squamous cell carcinomas (SCCs). The E6 protein of HPV is known to bind with p53 protein and inactive the tumor suppressor activity by promoting p53 degradation. Because of this background, we examined 38 primary, resected specimens of oral SCCs for detection of p53 mutations and HPV DNAs. Exons 5 through 8 of the p53 Mutations were observed in nine cases (24%). HPV-DNA detection and typing were performed using PCR with ¿high risk group' HPV-specified primers. HPV DNA sequences were detected in eight cases (21%). The AvaII digestion pattern of PCR-amplified HPV DNA showed that HPV-16 was present in all eight cases. Seven cases were p53 mutation-positive/HPV-negative, six cases were p53 mutation-negative/HPV-positive, and two intraosseus SCC cases were p53 mutation-positive/ HPV-positive. Thus, 15/38 (40%) cases had inactivation of the p53 protein. Interestingly, p53 mutation-negative/ HPV-negative cases had a poorer prognosis than p53 mutation positive or HPV-positive cases (P < 0.01). We conclude that (1) mutation in the p53 gene and/or HPV infection are frequent (40%) in oral SCC; (2) inactivation of p53 function by mutation and HPV infection are important genetic events in the development of 40% integral of oral SCCs; (3) p53 mutation and HPV infection are not mutually exclusive events and (4) other oncogenes or tumor suppressor genes may be crucial in the development of oral SCC if the prognosis is poor.

Aged↗

PubMed1996

Changes in regional cerebral blood flow during self-paced arm and finger movements. A PET study.

The purpose of this study was to identify the functional fields activated in relation to the self-paced proximal and distal arm movements. The regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and 15O-labelled H2O (H2(15)O) in eight healthy subjects. All subjects performed the following three tasks: (1) repetitive opposition of thumb and index finger of the right hand, (2) repetitive co-contraction of biceps and tricepts brachii muscles of the right arm, and (3) rest. The mean rCBF change images for each task minus control was calculated and fields of significant rCBF changes were identified. Each movement activated different fields in the primary motor area (MI), the dorsal aspect of the premotor area (PMA) and the superior part of the prefrontal area (PFA) of the contralateral hemisphere. In these areas, arm fields were located relatively dorsally to the finger fields. In addition, specific fields in the ventral part of the PMA, the supplementary motor area (SMA), the superior parietal lobule (SPL) of the contralateral hemisphere, and the ipsilateral PFA were consistently activated during both movements. Due to a limited a field of view of the PET scanner in the axial direction, the PET scan could not cover the cerebellum. The results indicate that there may be somatotopical organization not only in the MI but also in the dorsal part of the PMA and the PFA, and that the specific fields in the ventral part of the PMA, the SMA, the SPL, and the PFA may be involved in self-paced movement.

Adult↗

PubMed1996

Inhibition of protein serine/threonine phosphatases by fumonisin B1, a mycotoxin.

Fumonisin B1 (FB1), a mycotoxin produced by the fungus Fusarium moniliforme, which is a common contaminant of corn, is suspected to be a cause of human esophageal cancer. FB1 is hepatotoxic and hepatocarcinogenic in rats, and although the mechanisms involved have not been clarified, the latter is associated with a weak initiating activity. The effects of FB1 on the activity of protein serine/threonine phosphatases (PPs) (PP1, PP2A, PP2B, PP2C and PP5/T/K/H) were investigated in the present study. Inhibition of dephosphorylation was noted for all five PPs with IC50 values of 80 microM-3000 microM. Among the five PPs examined, PP5 was most sensitive with an IC50 of 80 microM. This concentration is comparable to that estimated to be reached in the rat body by feeding FB1 to obtain hepatic tumors. Inhibition of PP5 could thus play important roles in the toxicity and carcinogenic action of FB1.

Animals↗

PubMed1996

Distribution and subcellular localization of a growth inhibitory factor in hamster liver and its intracellular partner(s).

The subcellular, intralobular distributions and intracellular partner(s) of a factor which inhibits the proliferation of cell growth (Hashimoto C. et al. (1994) Biochim. Biophys. Acta 1221, 107-117) were determined in hamster livers, using a combination of immunological and biochemical techniques. The IgG fraction from an antiserum raised against the growth inhibitory factor with 37 kDa was shown to be highly specific for the antigen. The nuclear and cytosolic fractions demonstrated inhibitory effects on cell growth and Western blot analysis revealed that both fractions contained the immunoreactive 37 kDa protein with the anti-inhibitory factor IgG but microsomal and mitochondrial fractions did not. The nuclear and cytoplasmic localization of the inhibitory factor were further confirmed by immunochemical staining mediated through the immune IgG and an avidin-biotinylated horseradish peroxidase complex, the parenchymal liver cells were clearly stained, but endothelial and connective tissue cells were not. Although some staining was evident throughout the liver parenchyma, the hepatocytes with most intensively stained nuclei were located in the periportal region. In the liver from hamsters 6 days old or the regenerating hamster livers 3 days after partial hepatectomy, the staining intensity was low and the number of hepatocytes with the inhibitory factor positive nuclei was very few compared with the adult hamster livers. In primary cultures of the isolated hepatocytes from adult hamster the inhibitory factor disappeared from nuclei after incubation for 24-48 h. The extracts of hepatic nuclei from adult hamsters were immunoprecipitated with either the anti-growth inhibitory factor IgG or a monoclonal antibody to the RM protein. The growth inhibitory factor and the RB protein coprecipitated in each case, implying that the proteins were complexed with each other in the nuclei. The RB protein family is composed of two sets of species, an un- or underphosphorylated species and a hyperphosphorylated one. It was suggested that the factor bound preferentially to the un- or underphosphorylated member of the family.

Animals↗

PubMed1996

Changes in rCBF during grasping in humans examined by PET.

To identify the functional fields involved in grasping for objects, we measured regional cerebral blood flow (rCBF) by positron emission tomography (PET) in eight normal volunteers. In the reaching and grasping tasks, the subjects were asked to touch or grasp one of five cylinders with their finger(s). Compared with reaching, grasping specifically increased the rCBF in the fields located in the bilateral premotor area (PMA), the posterior parietal area (PPA) and the prefrontal area (PFA). These results indicate that PMA, PPA and PFA might be key structures for the performance of grasping movements.

Adult↗

PubMed1996

Insulin- and polyunsaturated fatty acid-responsive region(s) of rat ATP citrate lyase gene promoter.

To investigate the regulatory DNA sequences required for insulin-stimulation of the ATP citrate-lyase (ACL) gene as well as for polyunsaturated fatty acid (PUFA)-suppression of this gene, primary cultured hepatocytes were transfected with plasmids containing the 5'-flanking sequence of the rat ACL gene fused to the chloramphenicol acetyltransferase (CAT) gene. Sequences from -861, -194 or -104 to +128 of the ACl gene directed an increase in CAT activity in hepatocytes when insulin was added to the medium containing either glucose or pyruvate. The CAT activities stimulated by insulin were reduced by the addition of PUFA, in accordance with the responses on the endogenous ACL gene expression. Further deletion to -20, however, resulted in loss of the responses. The results suggest that the region from -104 to -20 of the ACL gene is responsible for regulation due to insulin and PUFAs. In particular, the region from -61 to -49 of the ACL has sequence similarity to the insulin-responsive regions of fatty acid synthase and acetyl-CoA carboxylase.

ATP Citrate (pro-S)-Lyase↗

PubMed1996

Vocal fold vibration in simulated head voice phonation in excised canine larynges.

In order to establish precise vibratory patterns and their clinical implication for phonation, the mode of vibration of the vocal folds around the time of register transition in excised canine larynges was analyzed multi-directionally according to various acoustic parameters. Phonation was simulated by artificially tensing the cricothyroid muscles. Vibration of the vocal folds around the time of register transition was filmed from above using ultra-high-speed cinematography and in a frontal plane using X-ray stroboscopy. Acoustic parameters included subglottic pressure, pitch, intensity and tension and were recorded simultaneously during register transition. The fundamental vibration patterns observed during vocal phonation were the same as that involved in chest voice phonation in excised canine larynges, with respect to the traveling wave of the vocal fold vibration. Changes in the physical properties of the vocal folds were considered to occur at register transition. These changes were probably strongly dependent upon changes in the structure of the lamina propria. Head voice phonation requires adaptability of the lamina propria and is less efficient than chest voice phonation. Hence, head voice phonation would be one method for assessing the condition of the vocal folds.

Animals↗

PubMed1996

A simple method for the quantification of benzodiazepine receptors using iodine-123 iomazenil and single-photon emission tomography.

Iodine-123 iomazenil (Iomazenil) is a ligand for central type benzodiazepine receptors that is suitable for single-photon emission tomography (SPET). The purpose of this study was to develop a simple method for the quantification of its binding potential (BP). The method is based on a two-compartment model (K1, influx rate constant; k2', efflux rate constant; VT' (=K1/k2'), the total distribution volumes relative to the total arterial tracer concentration), and requires two SPET scans and one blood sampling. For a given input function, the radioactivity ratio of the early to delayed scans can be considered to tabulate as a function of k2', and a table look-up procedure provides the corresponding k2' value, from which K1 and VT' values are then calculated. The arterial input function is obtained by calibration of the standard input function by the single blood sampling. SPET studies were performed on 14 patients with cerebrovascular diseases, dementia or brain tumours (mean age+/-SD, 56.0+/-12.2). None of the patients had any heart, renal or liver disease. A dynamic SPET scan was performed following intravenous bolus injection of Iomazenil. A static SPET scan was performed at 180 min after injection. Frequent blood sampling from the brachial artery was performed on all subjects for determination of the arterial input function. Two-compartment model analysis was validated for calculation of the VT' value of Iomazenil. Good correlations were observed between VT' values calculated by three-compartment model analysis and those calculated by the present method, in which the scan time combinations (early scan/delayed scan) used were 15/180 min, 30/180 min or 45/180 min (all combinations: r=0.92), supporting the validity of this method. The present method is simple and applicable for clinical use.

Brain↗

PubMed1996

Inhibition of GABAA ligand-gated Cl- channels by zinc in adult rat brain: a regional study.

Zinc (Zn2+) was shown to invariably inhibit muscimol-stimulated 36Cl- uptake by synaptoneurosomes in the cerebral cortex, hippocampus and cerebellum. The Zn2+ sensitivity of the GABAA receptor-gated 36Cl- uptake in the cerebral cortex was comparable to that in the hippocampus, whereas the uptake in the cerebellum was less sensitive to Zn2+. Although diazepam-potentiation of muscimol-stimulated 36Cl- uptake was unaltered by 100 microM Zn2+ in the cerebral cortex and hippocampus, diazepam caused no enhancement in the presence of Zn2+ in the cerebellum. Zn2+ inhibited [3H]diazepam binding significantly at 1 mM in the cerebral cortex and cerebellum, whereas Ni2+ increased the binding in a concentration-dependent manner in both regions. Although lower concentrations of Zn2+ did not affect [3H]Ro 15-4513 binding to diazepam-sensitive sites, higher concentrations of ZN2+ increased the binding in both regions. Unlike the diazepam-sensitive sites, the diazepam-insensitive [3H]Ro 15-4513 binding was not affected by Zn2+ or Ni2+ at any of the tested concentrations. These results suggest that the GABAA ligand-gated Cl- flux and its diazepam-potentiation are heterogeneously modulated in various brain regions. It is also suggested that cerebellar diazepam-insensitive [3H]Ro 15-4513 binding sites are insensitive to Zn2+ and Ni2+.

Animals↗

PubMed1996

Failed spinal anaesthesia: cause identified by MRI.

PURPOSE: To determine the cause of failed spinal anaesthesia, magnetic resonance images of the lumbar spine were examined. CLINICAL FUTURES: A 28-yr-old woman, scheduled for closure of a rectal fistula under spinal anaesthesia, hyperbaric tetracaine 12.5 mg injected into the subarachnoid space at L3-4 repeatedly resulted in restricted sacral spread. Magnetic resonance imaging showed that the cylindrical dimension of the lumbar spinal canal was wider than in normal subjects, suggesting a larger volume of CSF within the dural sac below the termination of the cord. The summit of the lumbar convexity was located at L3, which was more cephalad than the L3-4 puncture site. CONCLUSION: The uncommon anatomical characteristics of the lumbar spinal canal identified by magnetic resonance imaging were considered to be the reason for the restricted sacral spread observed repeatedly in this patient.

Adult↗

PubMed1996

Sevoflurane anaesthesia for a patient with adult polyglucosan body disease.

PURPOSE: Adult polyglucosan body disease (APBD) is a rare neurological disorder of unknown cause characterized by four manifestations: upper motor neuron signs, peripheral neuropathy with motor and sensory loss, urinary incontinence, and dementia. The purpose of this report is to present a patient with APBD anaesthetized successfully with sevoflurane and nitrous oxide. CLINICAL FEATURE: A 51-yr-old man with APBD was scheduled for haemorrhoidectomy. Paraesthesia, dysaesthesia, distal muscular atrophy and fasciculation were recognized in the extremities. Dementia, bulbar paralysis and respiratory insufficiency were basent. Anaesthesia was induced with inhalation of sevoflurane and nitrous oxide, and the trachea was intubated without the use of muscle relaxants. Maintenance of anaesthesia was performed with sevoflurane (inspired concentration: 1.5-2.5%) and nitrous oxide (50%). Emergence from anaesthesia and the postoperative course were uneventful, and no exacerbation of neurological signs and symptoms was recognized. No postoperative analgesia was required. CONCLUSION: General anaesthesia and tracheal intubation with sevoflurane and nitrous oxide provided safe anaesthesia for a patient with APBD.

Anesthesia↗

PubMed1996

Partial-thickness tears of the rotator cuff. A clinicopathological review based on 66 surgically verified cases.

This review is based on 66 patients with partial-thickness tears of the rotator cuff, verified at operation. Their average age was 54 years, and all had symptoms of subacromial impingement. The duration of shoulder pain was for between 2 and 108 months (mean 11.4 months). Ultrasonography, arthrography and bursography were helpful in establishing the diagnosis. On exploration, tears were found in the supraspinatus tendon, with 9 extending into the infraspinatus. After anterior acromioplasty, excision of the diseased portion and tenorrhaphy were undertaken. Satisfactory results were obtained in 62 patients (94%) with an average follow-up of 32 months. Spontaneous repair at the torn site was never seen. In addition to Neer's staging of impingement, we propose a new classification based on the integrity of the cuff tendon. We conclude that a partial-thickness cuff tear is an important cause of shoulder disability, which deserves much more clinical attention; misdiagnosis is common and leads to mismanagement. When conservative treatment fails, accurate diagnosis and proper surgical repair are essential.

Adult↗

PubMed1996

gamma-Butyrolactone-induced absence-like seizures increase nuclear CRE- and AP-1 DNA-binding activities in mouse brain.

We examined the involvement of the GABAB receptor and the coordinated induction of nuclear transcriptional factors in experimental generalized absence seizures induced by gamma-butyrolactone (GBL) in mice. Although administration of GBL 50 mg/kg did not show any effects on behavior or ECoG pattern, higher doses of GBL (70 and 100 mg/kg, i.p.) induced behavioral changes associated with 3-6-Hz spike and wave discharges in the mice. CGP 35348, a GABAB receptor antagonist, suppressed both the GBL-induced absence seizures and the spike and wave discharges. The antiepileptic effects of CGP 35348 (200 mg/kg, i.p.) were stronger than those of ethosuximide (200 mg/kg, i.p.). Sodium valproate (100 mg/kg, i.p.) attenuated the early phase but not the late phase of the GBL-induced absence seizures. Gel-mobility assay demonstrated that administration of an effective dose of GBL for eliciting spike and wave discharges dose-dependently increased nuclear cyclic AMP-responsive element (CRE)- and activator protein 1 (AP-1) DNA-binding activities in mouse whole brain. The increases in nuclear CRE- and AP-1 DNA-binding were antagonized by CGP 35348 in a dose-dependent fashion. In addition, GABAB receptor binding assay revealed that GBL or antiepileptic drugs did not displace [3H]baclofen binding in cerebral cortical membranes. In contrast, gamma-hydroxybutyrate (GHB), an active metabolite of GBL, inhibited [3H]baclofen binding in a concentration-dependent manner. These results suggest that GABAB receptor-mediated synaptic responses are involved in GBL-induced generalized absence seizures and that the increases in nuclear CRE- and AP-1 DNA-binding activities are correlated with the GBL-induced generalized absence seizures.

4-Butyrolactone↗

PubMed1996

Identification of peptides mimicking the antigenicity and immunogenicity of conformational epitopes on Japanese encephalitis virus protein using synthetic peptide libraries.

Monoclonal antibodies (mAbs) N.03 and N.08 that recognize conformational epitopes on the prM protein of Japanese encephalitis virus (JEV) were analyzed to identify their peptide ligands by using a novel approach that combined two different synthetic peptide libraries. Immunoscreening of a library containing 20(5) sequences of pentapeptides revealed that the ligands for N.03 and N.08 had motif sequences, (Y/W/F)GG(I/L/M) and (N/Q)WY(D/E), respectively. To select higher-affinity ligands, we synthesized and screened another type of library with 20 peptide mixtures that were based on the identified motif, where only one amino acid position was defined; and the process was reiterated for the remaining undefined positions. Consequently, the peptides YGGIYMNG and QWYDDR were identified as peptide ligands of N.03 and N.08, respectively. These peptides bound specifically to the antigen-combining sites of the mAbs as confirmed by competitive binding assays. Mouse antisera directed against the peptide YGGIYMNG specifically recognized JEV, while those against QWYDDR did not. These data demonstrated that peptide ligands which reproduce or mimic the immunogenicity as well as the antigenicity of conformational epitopes can be at least partly identified using this approach. This approach may be useful for analyzing conformational epitopes, which are generally difficult to characterize, and might provide a step toward vaccine development when applied to protective mAbs.

Antigens, Viral↗

PubMed1996

Pericardial mesothelioma presenting as left atrial thrombus in a patient with mitral stenosis.

Primary pericardial mesothelioma is rare and remains a diagnostic and therapeutic challenge. Pericardial mesothelioma usually occurs independently of intracardiac lesions and infiltrates adjacent tissues superficially. An extremely rare case of malignant pericardial mesothelioma complicated by prior mitral valve surgery is reported. The tumour invaded the left atrium and mimicked a thrombus.

Diagnosis, Differential↗

PubMed1996

Ultrasonographic prediction of lethal pulmonary hypoplasia: comparison of eight different ultrasonographic parameters.

OBJECTIVE: The aim of this study was to determine the usefulness of eight different ultrasonographic fetal parameters for predicting fetal pulmonary hypoplasia. STUDY DESIGN: Nomograms of eight different ultrasonographic fetal parameters were evaluated by studying uncomplicated single fetus pregnancies with well-established dates between 18 and 40 weeks of gestation. The eight parameters, which could reflect fetal lung mass, were as follows: thoracic circumference, thoracic area, thoracic area minus heart area, lung area, thoracic circumference/abdominal circumference ratio, thoracic area/heart area ratio, thoracic area minus heart area/thoracic area ratio and lung area/thoracic area ratio. The relative efficacy of the eight parameters was determined by studying 21 fetuses at high risk for development of lethal pulmonary hypoplasia and 30 fetuses with premature rupture of membranes within 1 week. RESULTS: The lung area (gestational age-dependent parameter) and the thoracic circumference/abdominal circumference (gestational age-independent parameter) ratio had the best diagnostic accuracy (sensitivity 81.3% and 90.5%, specificity 100% and 90.0%, positive predictive value 100% and 86.4%, negative predictive value 90.9% and 93.1%, respectively). There were significant linear relationships between lung weight and lung area and between the lung weight/body weight ratio and the thoracic circumference/abdominal circumference ratio. CONCLUSION: These data suggested that the application of lung area and the thoracic circumference/abdominal circumference ratio are clinically useful for the evaluation of fetal pulmonary hypoplasia.

Abdomen↗

PubMed1996

Attenuation of cardiopulmonary bypass-derived inflammatory reactions reduces myocardial reperfusion injury in cardiac operations.

In cardiac operations endopeptidase (protease) inhibitor may be beneficial in reducing myocardial injury when administered in the cardiopulmonary bypass prime. Nafamostat mesilate was evaluated in 20 patients who underwent coronary artery bypass grafting. The patients were divided into a control group (n = 10) and a nafamostat group (n = 10). Nafamostat (2 mg/kg per hour) was continuously given during cardiopulmonary bypass in the nafamostat group. The age, number of grafts, cardiopulmonary bypass time, and aortic crossclamp time were similar between groups. In the control group, neither tumor necrosis factor-alpha nor interleukin-1 levels showed any significant change during cardiopulmonary bypass, whereas interleukin-6 and interleukin-8 levels, percent expression of adhesion molecule (CD18) on neutrophils, and CH50 assay results increased significantly during cardiopulmonary bypass. As compared with the control group, the nafamostat group showed significantly lower levels of interleukin-6 (123 +/- 57 versus 40 +/- 22 pg/ml, respectively) and interleukin-8 (96 +/- 13 versus 66 +/- 14 pg/ml, respectively). The nafamostat group showed a significantly lower difference of CH50 assay results and malondialdehyde levels between coronary sinus blood and arterial blood and peak values of creatine kinase MB (43 +/- 12 IU/L versus 19 +/- 6 IU/L) during the postoperative course compared with findings in the control group. These results demonstrated that inflammatory reactions induced by cardiopulmonary bypass had adverse effects on myocardial recovery after aortic crossclamping and that nafamostat mesilate given during cardiopulmonary bypass appeared to reduce myocardial reperfusion injury by attenuating such inflammatory reactions. Attenuation of inflammatory reactions of cardiopulmonary bypass should be considered in the strategy of myocardial protection.

Benzamidines↗