Search PubMed⌕ Search

Biomedical subjects

H Fukuda

Publications and source records attributed to H Fukuda.

At least 361 records · Page 20Linked to original sources
PubMed1998

[Remarkable increase of CD8+ CD11a+ and CD8+ CD57- T cells in patients with post-transfusion graft-versus-host disease].

We analyzed the distribution of two T cell subsets, CD8+ CD11a+ (CD8+ cytotoxic effector population) and CD8+ CD57- cells, in the peripheral lymphocytes of 3 post-operative patients with post-transfusion graft-versus-host disease (PT-GVHD) and 5 post-operative patients without PT-GVHD. The percentage of CD8+ CD11a+ cells in the PT-GVHD-negative control was 19 +/- 4%, and in the 3 patients with PT-GVHD, 69%, 66%, and 59%, respectively. The percentage of CD8+ CD57- cells in the PT-GVHD-negative control was 19 +/- 6%, and in the 3 PT-GVHD patients, 59%, 58%, and 55%, respectively. Significantly higher proportions of the two T cell subsets were consistently observed in the patients with PT-GVHD than in the PT-GVHD-negative control. These results suggest that the analysis of CD8+ T cell subsets may be useful for the simple and rapid laboratory diagnosis of PT-GVHD.

Acute Disease↗
PubMed1998

[Relationship of utilization rate of health examination under the Elderly Act to medical expenditure and days of medical care for the elderly].

The aim of this study was to investigate the relationship of utilization rate of health examination to medical expenditure and days of medical care per insured person under the Elderly Act. The factors related with the utilization rate of health examination were also analyzed by multiple regression analysis. The material used in this analysis was the 1993 national health insurance data for all of the 3,252 municipalities of Japan. The main results were as follows: 1. The average medical expenditure and days of medical care among the municipalities declined in the increasing order of the three categories of utilization rate of health examination; municipalities with utilization rate of less than 30% being the highest, and those with 50% or more being the lowest. 2. The average medical expenditure and days of medical care among the municipalities with community health centers were smaller than those without. 3. Multiple regression analysis showed that utilization rate had a positive relationship to percentage of elderly, presence of community health center, public financial power index, and number of public health nurses per resident. It had a negative relationship to the population and the number of clinical beds per resident. The number of public health nurses per resident was the most significant factor related with the utilization rate (standardized partial regression coefficient = 0.32). These results suggest that increasing the utilization rate of health examination and the number of community health centers could serve to lower medical expenditure and days of medical care through the promotion of the health services provided by municipalities.

Community Health Services↗
PubMed1998

Pharmacological profiles of absence seizure-induced increases in CRE- and AP-1 DNA-binding activities in gamma-butyrolactone-treated mice.

Absence seizures are characterised by a well-defined disturbance of thalamocortical function, and there is no spread to other systems. In this study, we continue our examination of the mechanisms underlying the increased nuclear cyclic AMP responsive element (CRE)- and activator protein 1 (AP-1) DNA-binding activities in a gamma-butyrolactone (GBL)-induced mouse model of absence seizure. The administration of GBL increased CRE- and AP-1 DNA-binding activities in the cerebral cortex and thalamus, but not in other regions such as the hippocampus, cerebellum or pons + medulla oblongata, at doses which induced absence seizures. Not only the absence-seizure behavior but also the increased CRE- and AP-1 DNA-binding activities in the thalamocortical regions were reversibly inhibited by ethosuximide, a typical anti-absence drug, and the GABAB antagonists CGP 35348 and CGP 46381. A gel-supershift assay revealed that the GBL-induced CRE-binding activity was supershifted by an anti-CRE-binding protein (CREB) antibody, and that AP-1 DNA-binding activity was blocked by anti-c-Jun and anti-c-Fos antibodies. These results suggest that increased CRE- and AP-1 DNA-binding activities in the cerebral cortex and thalamus are related to the pathogenesis of generalized absence seizures and that these increases in DNA-binding activity are related to ethosuximide- and GABAB antagonist-sensitive abnormal neuronal activity in the thalamocortical circuit.

4-Butyrolactone↗
PubMed1998

Potentiation of the 5-aminolevulinic acid-based photodynamic therapy with cyclophosphamide.

We have investigated the efficacy of the Photodynamic Therapy (PDT) from 5-aminolevulinic acid (ALA) in combination with an antineoplastic agent using an in vitro-in vivo model developed in our laboratory. The alkylant cyclophosphamide (CY) was chosen because there is evidence of the porphyrinogenic properties of this drug. Male BALB/c mice bearing a transplantable mammary adenoarcinoma were given two doses of 35 mg de CY/kg wt. i.p. and 9 mg/kg wt intratumorally. At 16, 22 and 40 hrs after the last injection of CY the animals were sacrificed and explants of 2 mg of tumor were incubated 2 hrs in a medium containing 0.6 mM ALA; and then irradiated with a He-Ne laser. Innocula of 1 mm3 of irradiated and non-irradiated tissue were then injected subcutaneously under the right and left flanks of a normal mouse, respectively. The efficacy of the treatment was determined following the growth of the tumor from day 10 after tumor implantation. Under the present conditions a 30% increased efficacy was observed in the case of the explants treated with CY 40 hrs after the last i.p. injection. Porphyrins in the liver and tumor and other tissues of the injected mice were also determined; except for a slight increase in tumor and liver, 40 and 22 hrs after CY i.p. injection respectively, no other changes were observed in any tissue, as compared with not CY treated mice. These results indicate that future treatment, combining the tumor localizing properties of endogenously formed porphyrins from ALA and antineoplasic drugs such as cyclophosphamide, should be encouraged.

Adenocarcinoma↗
PubMed1998

[Sevoflurane anesthesia for myotonic dystrophy].

We successfully anesthetized a 14-year-old boy with myotonic dystrophy for orthopedic surgery using sevoflurane. Sevoflurane enabled anesthetic induction and tracheal intubation without intravenous anesthetics and muscle relaxants. Sevoflurane also provided stable anesthetic maintenance without intravenous anesthetics. The patient showed rapid anesthetic recovery and adequate spontaneous breathing. We conclude that sevoflurane is a useful anesthetic for patients with myotonic dystrophy.

Adolescent↗
PubMed1997

Activity in the parietal area during visuomotor learning with optical rotation.

Regional cerebral blood flow (rCBF) was measured in six subjects to study changes of activity in the parietal cortex during learning of a visually guided pointing task with a discrepancy of visuomotor coordination and to determine whether reorganization affects the parietal activity after learning. During the early stage of learning, the right posterior parietal cortex showed a significant increase in rCBF. During the late stage, on the other hand, significant activation was noted in the postcentral gyrus of the right hemisphere. These results support a role for the posterior parietal cortex in remapping visuomotor coordinates and suggest the involvement of the human postcentral gyrus in retaining sensorimotor coordinates, considered to relate to the self image of the hand.

Adult↗
PubMed1997

Enhancement of aminolevulinic acid based photodynamic therapy by adriamycin.

This paper reports on studies that evaluate the interaction between delta-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) and adriamycin (ADM) in an animal model system. Two groups of mice bearing a transplantable mammary adenocarcinoma received ADM i.p. in a single dose of 5 mg (low dose) and 30 mg (high dose) per kg body weight. Sixteen or 40 h after administration of the drug, mice were sacrificed, tumours, livers and hearts were removed and porphyrins, enzyme activities and malondialdehyde content were determined. Tumour explants of ADM-treated mice were incubated with ALA and irradiated with an He-Ne laser. Re-implantation of these in vitro PDT-treated explants into test animals showed that inhibition of tumour growth was significantly enhanced by combined treatment when the low dose of ADM was used. There were no significant changes in porphyrin content, ALA dehydratase and porphobilinogenase activities in the tissues analyzed after ADM treatment as compared with control values. ADM toxicity is thought to be related to semiquinone free radical formation with subsequent generation of reactive oxygen species such as peroxide and hydroxyl radical. These species are considered to initiate lipid peroxidation (LPO) and cause DNA damage. In the case of low-dose treatment with ADM a significant increase in the LPO product, malondialdehyde, was observed after PDT whereas with the high-dose regimen no changes were observed. In the case of explants of (non-irradiated) cardiac tissue malondialdehyde production was also found to be dependent on the dose and time of administration of adriamycin. In our in vivo/in vitro model system we have shown that pre-treatment with ADM increased the cytotoxicity of ALA-PDT at a dosage level of ADM which did not raise LPO levels in heart tissue. The mechanism of this effect has not been clearly elucidated but our data suggest that the observed enhancement of PDT may be attributed in part to the weakening of cellular defence mechanisms by the pre-treatment involving free radical generation by ADM.

Adenocarcinoma↗
PubMed1997

Capsaicin in the 4th ventricle abolishes retching and transmission of emetic vagal afferents to solitary nucleus neurons.

Systemic tachykinin NK1 receptor antagonists and resiniferatoxin are known to abolish vomiting mediated by vagal afferents. Emetic vagal afferents have been shown to make synaptic contact with neurons in the medial solitary nucleus. These results suggest that substance P participates in the synapse as a mediator. To examine this possibility, the effects of 4th-ventricular application of capsaicin (0.033-33 mM, 20-30 microl) and resiniferatoxin (1.6-160 microM, 20-30 microl) on the activity of neurons in the medial solitary nucleus and fictive retching induced by vagal stimulation were observed in paralyzed decerebrate dogs. Capsaicin (33 mM) and resiniferatoxin (160 microM) initially increased the neuronal firing and occasionally produced retching, then abolished both neuronal and retching responses. However, stimulation of the medial solitary nucleus continued to provoke retching. Field potential changes in the medial solitary nucleus evoked by pulse-train vagal stimulation decreased in amplitude, but did not disappear. Latencies of neuronal firing and evoked potentials were about 300 ms. These results suggest that emetic vagal afferents are capsaicin-sensitive C fibers which may have substance P as an excitatory transmitter or modulator.

Animals↗
PubMed1997

Induction of minisatellite mutation in NIH 3T3 cells by treatment with the tumor promoter okadaic acid.

Okadaic acid (OA) is a strong tumor promoter of mouse skin carcinogenesis and also a potent inhibitor of serine/threonine protein phosphatases. OA induces various genetic alterations in cultured cells, such as diphtheria-toxin-resistance mutations, sister chromatid exchange, exclusion of exogenous transforming oncogenes, and gene amplification. The present study revealed that it caused minisatellite mutation (MSM) at a high frequency in NIH 3T3 cells, although no microsatellite mutation was found. Nine of 31 clones (29%) exhibited MSM after 6 days of OA treatment, as opposed to only 1 of 30 clones (3%) without OA exposure. Moreover, NIH 3T3 cells treated with OA acquired tumorigenicity in nude mice, giving rise to 7 tumors within 25 weeks in 20 sites where 3 x 10(6) cells were injected. In contrast, the same numbers of untreated cells gave rise to only one tumor, and the tumor grew much slower. All of three OA-induced tumors examined manifested the MSM. The findings thus point to a molecular mechanism by which OA could function as a tumor promoter, and also the biological relevance of the induction of MSM in the tumorigenic process by OA.

3T3 Cells↗
PubMed1997

Minisatellite instability in severe combined immunodeficiency mouse cells.

We have recently found that okadaic acid, which shows strong inhibitory activity on protein serine/threonine phosphatases and tumor-promoting activity in vivo and in vitro, induces minisatellite mutation (MSM). Human tumors and chemically induced counterparts in experimental animals are also sometimes associated with MSM. In the present study, we demonstrated minisatellite (MS) instability in severe combined immunodeficiency (SCID) cells in which the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is impaired. Cells from a SCID fibroblast cell line transformed by simian virus 40 large tumor antigen, SC3VA2, and from an embryonal SCID fibroblast cell line, SC1K, were cloned and propagated to 10(7) to 10(8) cells, and then subjected to subcloning. After propagation of each subclone to 10(7) to 10(8) cells, DNA samples were digested with HinfI and analyzed by Southern blotting using the Pc-1 MS sequence as a probe. Under low-stringency conditions, about 40 MS bands were detected, with 45% +/- 6% and 37% +/- 3% of SC3VA2 and SC1K cells, respectively, having MSM. In contrast, cells from the RD13B2 cell line, which was established from SCVA2 by introducing human chromosome 8q fragments, on which DNA-PKcs is known to reside, to complement the SCID phenotype, showed a very low frequency of MSM (3% +/- 3%). The high frequencies of MSM in SC3VA2 and SC1K were significant, with no difference between the two. The present study clearly demonstrates that MS instability exists in SCID fibroblasts, suggesting that DNA-PKcs might be involved in the stable maintenance of MS sequences in the genome.

Animals↗
PubMed1997

Production of granulocyte/macrophage and macrophage colony-stimulating factors by human thyrocytes in culture.

Monocytes/macrophages can be activated by the colony-stimulating factors (CSFs), granulocyte/macrophage CSF and macrophage CSF, and play a pivotal role in immune and inflammatory responses. We examined whether human thyrocytes can produce these CSFs. Interleukin-1 (IL-1) strongly up-regulated the gene and protein expression of the two CSFs. Interferon-gamma stimulated M-CSF expression but inversely suppressed GM-CSF expression in either basal or IL-1-stimulated condition. Thyrocytes prepared from Graves' thyroid tissues produced relatively larger amounts of GM-CSF in response to IL-1 and M-CSF in both basal and IL-1-stimulated conditions when compared to those obtained from normal and adenomatous goiter thyroid tissues. Thyrotropin attenuated M-CSF, but not GM-CSF, production. The present finding indicates that human thyrocytes themselves produce both GM-CSF and M-CSF, and thus may participate in immune and inflammatory responses through these CSFs production.

Cells, Cultured↗
PubMed1997

Vocal identification of speaker and emotion activates different brain regions.

Regional cerebral blood flow was measured in six healthy volunteers by positron emission tomography during identification of speaker and emotion from spoken words. The speaker identification task activated several audio-visual multimodal areas, particularly the temporal poles in both hemispheres, which may be involved in connecting vocal attributes with the visual representations of speakers. The emotion identification task activated regions in the cerebellum and the frontal lobe, suggesting a functional relationship between those regions involved in emotion. The results suggest that different anatomical structures contribute to the vocal identification of speaker and emotion.

Adolescent↗
PubMed1997

Descending pathway from the central pattern generator of vomiting.

The central pattern generator (CPG) for vomiting has been postulated to consist of non-respiratory neurons in the reticular area dorsomedial to the retrofacial nucleus. CPG neurons are known to produce vomiting activity patterns similar to respiratory spinal motoneurons and premotoneurons in the caudal part of the ventral respiratory group (cVRG). This study was performed to reveal direct connections between CPG neurons and cVRG neurons in dogs. Twenty-seven non-respiratory neurons were identified as CPG neurons based on their responses to vagal stimulation and their firing patterns of vomiting. Nine of these 27 neurons antidromically responded to cVRG stimulation. These results suggest that the CPG directly drives respiratory premotor neurons in the cVRG to produce vomiting motions.

Abdominal Muscles↗
PubMed1997

Most inspiratory neurons in the pre-Bötzinger complex are suppressed during vomiting in dogs.

Pulmonary ventilation is almost completely suppressed during actual retching. Correspondingly, respiratory activity either disappears or changes to retching activity in peripheral respiratory nerves and respiratory neurons of the Bötzinger complex and the caudal part of the ventral respiratory group. These results suggest the possibility that the respiratory rhythm generator is suppressed during retching. Recently, the pre-Bötzinger complex (pre-BOT) has been postulated to generate respiratory rhythm. To evaluate this possibility, the activities of pre-BOT neurons were observed during fictive retching and expulsion in decerebrate paralyzed dogs. Inspiratory (I) neurons in the pre-BOT consisted of pre-, early-, late-, post- and throughout-subtypes, as in cats and rats. Inspiratory firing almost completely disappeared during fictive retching in about 70% of the 158 pre-BOT I neurons examined, and changed to weak bursts produced either with retches or between retches in most of the remaining 30%. Similarly, all but one of the 21 I neurons examined did not produce any discharge with fictive expulsion. In contrast, all of the pre-BOT expiratory and inspiratory-expiratory neurons examined produced vigorous bursts either with retches or between retches, and with expulsion. These results suggest that inspiratory outputs from the respiratory rhythm generator are almost completely suppressed during retching and expulsion, and that expiratory outputs change to retching and expulsion activities.

Animals↗
PubMed1997

Transcriptional regulatory region for expression of the rat ATP citrate-lyase gene.

We previously mapped the sequences responsive to insulin/glucose stimulation and polyunsaturated fatty-acid suppression in the proximal promoter region between positions -104 and -20 of the ATP citrate-lyase (ACL) gene [Fukuda, H., Iritani, N., Katsurada, A. & Noguchi, T. (1996) FEBS Lett. 380, 204-207]. To investigate further the regulatory DNA sequences required for stimulation and suppression of this gene, primary cultured hepatocytes were transfected with plasmids containing the 5'-flanking sequences of the rat ACL gene fused to the chloramphenicol acetyltransferase (CAT) gene. When two copies of the sequences spanning -64 to -41 (linked to ACLcat20) were used for transfection, CAT activity significantly increased in response to insulin/glucose treatment. This increase was inhibited by addition of polyunsaturated fatty acid. Mutational analysis of this region showed that sequences between -55 and -51 are essential for recognition and interaction with trans-acting factors. Gel mobility shift assays using the sequence from -64 to -41 as a probe revealed nuclear factor(s) from rat liver that specifically complexed with the sequences. In addition, by antibody supershift assays, we have detected the binding of the transcriptional factor Sp1 at the G+C-rich region located within -64 to -41 of the ACL promoter. On the other hand, the formations of DNA-protein complexes with Sp1 binding site or ACL(-64 to -41) were decreased in rats fed a high-carbohydrate diet in comparison with those in rats fasted or fed a polyunsaturated fatty-acid-rich diet. Cotransfection studies in rat hepatocytes, with the Sp1 expression vector and ACLcat constructs, showed the inactivation of the promoter. These results demonstrated that the region from -64 to -41 of the ACL gene was responsible for stimulation due to insulin/glucose, the stimulation was suppressed by polyunsaturated fatty acid, and Sp1 may be involved in the regulation.

ATP Citrate (pro-S)-Lyase↗
PubMed1997

Functional asymmetry of cortical motor control in left-handed subjects.

We used positron emission tomography (PET) to investigate which cortical motor areas are active in relation to unilateral dominant or non-dominant finger movements in left-handed subjects. The right premotor area was activated by both contralateral and ipsilateral finger movements, in contrast to the primary motor, the left premotor and supplementary motor areas in which activation was only by contralateral movements. Bilateral finger movements activated all of these areas. We conclude that there exists cortical asymmetry for motor control in left-handers which is different from that apparent in right-handers.

Adolescent↗
PubMed1997

Transcriptional regulatory regions for expression of the rat fatty acid synthase.

We previously mapped the sequences responsive to insulin/glucose stimulation and polyunsaturated fatty acid (PUFA) suppression in proximal promoter region from -57 to -35 of fatty acid synthase (FAS) gene of rat liver [Fukuda et al. (1996) Biochem. Mol. Biol. Int. 38, 987-9961. When two copies of the sequences spanning -57 to -35 were linked to a reporter gene containing heterologous promoter and were used for transfection, the reporter activity significantly increased in response to insulin/glucose treatment in hepetocytes. This increase was inhibited by addition of PUFA. Gel mobility shift assays using the sequence from -57 to -35 as a probe revealed nuclear factor(s) from rat liver that specifically complexed with the sequences. In addition, by antibody supershift assays, we have detected the binding of the transcriptional factor Sp1 at the GC-rich region located within -57 to -35 of the FAS promoter. Cotransfection studies in rat hepatocytes, with the Sp1 expression vector and FAScat constructs, showed the inactivation of the promoter. These results were similar to those for the region from -68 to -52 of FAS gene (an insulin response element). The region from -68 to -52 of FAS gene competed for the formation of DNA-protein complexes to the region from -57 to -35 in the gel shift assay. Mutational analysis showed that the overlapping region of these two sequences was essential for the binding of Sp1. It has been demonstrated that both the regions from -57 to -35 and from -68 to -52 of the FAS gene are responsible for regulation due to insulin/glucose and PUFA, and Sp1 may be involved in the regulation.

Animals↗