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Biomedical subjects

A Fukuda

Publications and source records attributed to A Fukuda.

At least 37 records · Page 2Linked to original sources
PubMed2001

Probable Langevin-like director reorientation in an interface-induced disordered SmC*-like state of liquid crystals characterized by frustration between ferro- and antiferroelectricity.

To clarify the thresholdless, hysteresis free V-shaped switching due to frustration between ferro- and antiferroelectricity, we have studied a prototype binary mixture system. The apparent orientational order parameters, and , obtained from polarized Raman scattering in thin homogeneous cells indicate that substrate interfaces induce some randomization of local in-plane directors at the tip of the V. Their correlation lengths, xi( parallel) approximately 3.5 nm and xi( perpendicular) approximately 75 nm, have been estimated by assuming the Langevin-like reorientation. Because of the much shorter xi(parallel) and xi(perpendicular) than the visible light wavelength, the switching process looks uniform.

Journal Article↗
PubMed2001

Differential expression of metastasis-associated genes in papilla of vater and pancreatic cancer correlates with disease stage.

PURPOSE: Papilla of Vater cancer has a much better prognosis than pancreatic cancer. It is not known whether this is the result of differences in the tumor biology of the two malignancies. Because metastasis formation is a critical step in tumor progression and a negative prognostic factor, we compared the expression of nm23-H1 and KAI1, two metastasis-suppressing genes, in papilla of Vater cancer and pancreatic cancer. PATIENTS AND METHODS: Analysis was performed in nine normal human papilla of Vater samples, 27 papilla of Vater cancers, 16 normal pancreatic samples, and 29 pancreatic cancers. Expression of nm23-H1 and KAI1 was analyzed by Northern blot analysis and in situ hybridization. In addition, immunohistochemistry was performed to localize the respective proteins. RESULTS: There was no difference in nm23-H1 and KAI1 mRNA expression levels in normal versus cancerous papilla of Vater samples. In contrast, nm23-H1 and KAI1 RNA expression was upregulated in early tumor stages of pancreatic cancer and reduced in advanced tumor stages. When expression of nm23-H1 and KAI1 RNA was analyzed by use of in situ hybridization, normal epithelial cells of the papilla of Vater exhibited mRNA staining intensity similar to that of papilla of Vater cancer cells. Similar levels of nm23-H1 and KAI1 immunoreactivity also were observed in these samples. In contrast, early stage pancreatic cancer samples exhibited stronger nm23-H1 and KAI1 immunoreactivity than normal controls. Furthermore, early pancreatic cancer stages exhibited higher KAI1 and nm23-H1 immunostaining than advanced tumor stages. CONCLUSION: Differences in the expression patterns of the two tumor suppressor genes nm23-H1 and KAI1 may contribute to the different prognoses of papilla of Vater cancer and pancreatic cancer. Our findings support the hypothesis that biologic differences rather than earlier diagnosis influence the different outcomes of these two tumor entities.

Adolescent↗
PubMed2001

Inhibitory effect of pentalenolactone on vascular smooth muscle cell proliferation.

The effect of pentalenolactone, an inhibitor of glyceraldehyde-3-phosphate dehydrogenase, on rat vascular smooth muscle cell proliferation was studied. Addition of pentalenolactone together with serum to quiescent cells dose-dependently inhibited cell proliferation and DNA synthesis. This inhibition was not associated with cell death. When quiescent cells were stimulated with serum and then treated with pentalenolactone, the inhibitory effect on the DNA synthesis declined gradually. A similar result was obtained when PD 98059 (2'-amino-3'-methoxyflavone), an inhibitor of extracellular signal-regulated kinase1/2 (ERK1/2) kinase (MEK1/2), was added to the cells after serum stimulation. Pentalenolactone inhibited serum or protein kinase C activator (phorbol 12,13-dibutyrate)-induced phosphorylation of ERK1/2 and MEK1/2. In contrast, pentalenolactone had little effect on platelet-derived growth factor receptor autophosphorylation. Taken together, these results indicate that pentalenolactone inhibits vascular smooth muscle cell proliferation, and that this inhibition appears to be mediated by inhibition of the ERK1/2 cascade.

3T3 Cells↗
PubMed2001

Acute adrenal infection by HSV-1: role of apoptosis in viral replication.

Replication of herpes simplex virus type 1 (HSV-1) in the adrenal gland of mice was observed 12 h after intravenous inoculation, peaked at 48 h (7 x 10(7) PFU/tissue), and was maintained until death. Virus spread to the bilateral intermediolateral column of the thoracic spinal cord. Infected cells appeared in the fascicular zone of the adrenal cortex 12 h after infection, and cell death was evident in lesions found in the adrenal cortex. Lesions involved the medulla 48 h after inoculation. In cortical lesions, cell nuclei were fragmented or shrunken with little damage to the cytoplasm. DNA fragmentation appeared 12 h after inoculation and increased mainly in cortical lesions, which were characterized by apoptosis induced by HSV-1 infection. In the adrenal medulla, cells were fused and formed multinucleated giant cells but rarely displayed cell death. Macrophages, which serve as a frontal barrier to viral infection in the adrenal gland, especially the cortex, were fewer in number than those found in the liver or spleen. It is likely that HSV-1 easily infects the adrenal gland, resulting in suppression of local immunity, and that adrenal cell apoptosis serves as a primitive type of immunity to limit viral replication.

Acute Disease↗
PubMed2001

Identification of sequence polymorphisms in two sulfation-related genes, PAPSS2 and SLC26A2, and an association analysis with knee osteoarthritis.

Osteoarthritis (OA) is one of the most common musculoskeletal disorders and is characterized by degeneration of articular cartilage. Sulfation of extracellular matrix proteins in articular cartilage is an important step in maintaining normal cartilage metabolism. Two sulfation-related genes have been reported as the causal genes of severe chondrodysplasias: mutations in PAPSS2 (3'-phosphoadenosine 5'-phosphosulfate synthase 2) cause spondylo-epimetaphyseal dysplasia (SEMD), and mutations in SLC26A2 (solute carrier family 26, member 2) cause diastrophic dysplasia. Given their critical roles in cartilage metabolism and the severe phenotypes that result from mutations in these genes, we examined PAPSS2 and SLC26A2 as candidate susceptibility loci for OA. We identified sequence polymorphisms in the coding and core promoter regions of these genes and analyzed their potential association with knee OA within the Japanese population. Ten sequence polymorphisms were detected in PAPSS2 and five in SLC26A2. An association analysis showed suggestive association of one minor polymorphism in the promoter region of SLC26A2. This 4-bp adenine deletion allele, del4A, was over-represented in knee OA (P = 0.043, odds ratio = 3.43) and is thought to confer a minor susceptibility to knee OA within the Japanese population. Haplotype analysis showed no evidence of association with the two genes, however, excluding them as major susceptibility loci for knee OA.

Anion Transport Proteins↗
PubMed2001

Identification of sequence polymorphisms of the COMP (cartilage oligomeric matrix protein) gene and association study in osteoarthrosis of the knee and hip joints.

Osteoarthrosis (OA) is a common cause of musculoskeletal disability characterized by late-onset degeneration of articular cartilage. Although several candidate genes have been reported, susceptibility genes for OA remain to be determined. Hereditary osteochondral dysplasias produce severe, early-onset OA and hence are models for common idiopathic OA. Among them are pseudoachondroplasia and multiple epiphyseal dysplasia, both of which are caused by mutations in the cartilage oligomeric matrix protein (COMP) gene. Therefore, COMP may be a susceptibility gene for OA. We screened for polymorphisms by direct sequencing of all exons of the COMP gene with their flanking intron sequences and the promoter region. We identified 16 polymorphisms, of which 12 were novel. Using six polymorphisms spanning the entire COMP gene, we examined the association of COMP in Japanese patients with OA of the knee and hip joints. Genotype and allele frequencies of the polymorphisms were not significantly different between OA and control groups, and there was no significant difference in haplotypes. These results do not support an association between COMP and OA in the Japanese population.

Cartilage↗
PubMed2001

Aspirin dose dependently inhibits the interleukin-1 beta-stimulated increase in inducible nitric oxide synthase, nitric oxide, and prostaglandin E(2) production in rat ovarian dispersates cultured in vitro.

OBJECTIVE: Determine if aspirin inhibits the IL-1 beta-stimulated expression of inducible nitric oxide synthase (iNOS), nitric oxide (NO), and prostaglandin E(2) (PGE(2)) in rat ovarian dispersates cultured in vitro. DESIGN: Prospective, controlled in vitro study. SETTING: Academic research laboratory. ANIMALS: Ovaries collected from immature rats. INTERVENTION(S): Ovaries were collected from immature rats and enzymatically dispersed. Ovarian dispersates were placed into plates containing media alone or media supplemented with IL-1 beta (100 U/mL) and varying concentrations of aspirin (0, 1, 3, 5 and 10 mM). Ovarian dispersates were cultured in a humidified environment of 5% CO(2) in air at 37 degrees C for 24 or 48 hours. MAIN OUTCOME MEASURE(S): Twenty-four- and 48-hour iNOS, nitrite (a stable metabolite of NO), and PGE(2) levels were determined from ovarian dispersates cultured in vitro. RESULT(S): Administration of IL-1 beta increased nitrite and PGE(2) levels over that observed in the control group after culture of ovarian dispersates for 24 and 48 hours. Aspirin dose dependently reduced the IL-1 beta-stimulated increase in nitrite production from ovarian dispersates after culture for 24 and 48 hours. Aspirin completely (24 hours) or dose dependently (48 hours) prevented the IL-beta-stimulated increase in PGE(2.) Coadministration of IL-1 beta and aspirin (10 mM) attenuates IL-1 beta-stimulated iNOS expression after culture for 24 and 48 hours. CONCLUSION(S): Aspirin significantly inhibits the IL-1 beta-stimulated expression of iNOS, NO, and PGE(2) in ovarian dispersates cultured in vitro.

Animals↗
PubMed2001

Optical imaging reveals cation--Cl(-) cotransporter-mediated transient rapid decrease in intracellular Cl(-) concentration induced by oxygen--glucose deprivation in rat neocortical slices.

In brain slices from young (postnatal day (P) 10--15) rat somatosensory cortex, real-time neuronal intracellular Cl(-) concentration ([Cl(-)](i)) recordings were made by an optical technique measuring 6-methoxy-N-ethlquinolinium iodide (MEQ) fluorescence. Oxygen--glucose deprivation (in vitro model of ischemia) induced a long-lasting [Cl(-)](i) increase preceded by a rapid, transient [Cl(-)](i) decrease that could not be inhibited by blockers of Cl(-) pumps, Cl(-) channels, or Cl(-) antiporters, but was sensitive to cation-Cl(-) cotransporter inhibitors (bumetanide and furosemide). Use of low external Na(+) or high external K(+) revealed that the Na(+),K(+)-2Cl(-) cotransporter was inhibited by bumetanide and furosemide, whereas the K(+)-Cl(-) cotransporter was preferentially inhibited by furosemide under our experimental conditions. With a reduced inward driving force for Na(+) (reducing Na(+),K(+)-2Cl(-) cotransport), the transient [Cl(-)](i) decrease was only rarely induced by oxygen-glucose deprivation. In contrast, with a reduced outward driving force for K(+) (reducing K(+)-Cl(-) cotransport), the transient [Cl(-)](i) decrease still occurred. These results suggest that the transient [Cl(-)](i) decrease was primarily mediated by a rapid inhibition of the inwardly directed Na(+),K(+)-2Cl(-) cotransporter. Reverse transcriptase-polymerase chain reaction (RT-PCR) experiments suggested that the isoform involved is NKCC1. We hypothesize that the initial rapid Cl(-) efflux might effectively delay the irreversible Cl(-) influx that mediates neuronal injury.

Animals↗
PubMed2001

The differential expression patterns of messenger RNAs encoding K-Cl cotransporters (KCC1,2) and Na-K-2Cl cotransporter (NKCC1) in the rat nervous system.

Cation-chloride cotransporters have been considered to play pivotal roles in controlling intracellular and extracellular ionic environments of neurons and hence controlling neuronal function. We investigated the total distributions of K-Cl cotransporter 1 (KCC1), KCC2 (KCC2), and Na-K-2Cl cotransporter 1 (NKCC1) messenger RNAs in the adult rat nervous system using in situ hybridization histochemistry. KCC2 messenger RNA was abundantly expressed in most neurons throughout the nervous system. However, we could not detect KCC2 messenger RNA expression in the dorsal root ganglion and mesencephalic trigeminal nucleus, where primary sensory neurons show depolarizing responses to GABA, suggesting that the absence of KCC2 is necessary for this phenomenon. Furthermore, KCC2 messenger RNA was also not detected in the dorsolateral part of the paraventricular nucleus, dorsomedial part of the suprachiasmatic nucleus, and ventromedial part of the supraoptic nucleus where vasopressin neurons exist, and in the reticular thalamic nucleus. As vasopressin neurons in the suprachiasmatic nucleus and neurons in the reticular thalamic nucleus produce their intrinsic rhythmicity, the lack of KCC2 messenger RNA expression in these regions might be involved in the genesis of rhythmicity through the control of intracellular chloride concentration. The expression levels of KCC1 and NKCC1 messenger RNAs were relatively low, however, positive neurons were observed in several regions, including the olfactory bulb, hippocampus, and in the granular layer of the cerebellum. In addition, positive signals were seen in the non-neuronal cells, such as choroid plexus epithelial cells, glial cells, and ependymal cells, suggesting that KCC1 and NKCC1 messenger RNAs were widely expressed in both neuronal and non-neuronal cells in the nervous system. These results clearly indicate a wide area- and cell-specific variation of cation chloride cotransporters, emphasizing the central role of anionic homeostasis in neuronal function and communication.

Animals↗
PubMed2001

Suppression of fibrous adhesion by proteoglycan decorin.

Small proteoglycan decorin is known to suppress the bioactivity of TGF-beta through a competitive binding with the cell surface receptors for the cytokine. Based on this knowledge, we hypothesized that decorin could reduce the formation of fibrous adhesion, because our previous study showed the neutralizing antibody to TGF-beta1 has that effect. An intra-articular adhesion model in the rabbit knee joint was employed in this study, and decorin was administered into the joint cavity continuously during the 4 weeks of the experiment. The results of the dose-response study demonstrated that decorin suppresses formation of fibrous adhesion in a dose-dependent manner. When the administration of decorin was limited to shorter periods, this effect was considerably impaired and the necessity of long-term administration was demonstrated. On the other hand, when administered together with TGF-beta1, decorin still suppressed adhesion but to a lesser extent, and it was suggested that this proteoglycan could have other significant mechanism(s) to suppress adhesion besides the neutralization of TGF-beta. Thus, the present study showed that decorin could inhibit adhesion formation by both TGF-beta dependent and independent mechanisms. Considering that decorin exists ubiquitously in the body, its administration might be a promising approach to suppress adhesion.

Animals↗
PubMed2001

Reconstitution of recombinant TFIIH that can mediate activator-dependent transcription.

BACKGROUND: TFIIH is one of the general transcription factors required for accurate transcription of protein-coding genes by RNA polymerase II. TFIIH has helicase and kinase activities, plays a role in promoter opening and promoter escape, and is also implicated in efficient activator-dependent transcription. RESULTS: We have established a reconstitution system of recombinant TFIIH using a three-virus baculovirus expression system. The recombinant TFIIH was active in CTD kinase and DNA helicase assays, and showed both basal and activator-dependent transcriptional activities that were indistinguishable from those of HeLa cell-derived TFIIH. Further analyses using recombinant TFIIH confirmed a critical role of TFIIH in activator-dependent transcription. The dose response of TFIIH in activator-dependent transcription suggested that mere recruitment of TFIIH is not sufficient for transcriptional activation. The sensitivity of activator-dependent transcription to nonhydrolysable ATP analogues indicated the importance of the enzymatic activities of TFIIH in transcriptional activation. CONCLUSIONS: Our results raise a possibility that transcriptional activation by GAL4-VP16 requires enzymatic activities. Recombinant TFIIH reconstituted from this baculovirus system should be useful for analysis of the mechanisms of activation by GAL4-VP16.

Adenosine Triphosphate↗
PubMed2001

Volume supplementation with iso-sodium solution prevents hypernatremia after head injury.

OBJECTIVE: To evaluate our developed volume supplement protocol in preventing hypernatremia after head injury. METHODS: Iso-sodium solution was infused to keep the 8-hour water balance positive in 20 head-injured patients with hypotonic urine. RESULTS: Serum sodium concentrations moved to within a normal range in 6 patients and were temporarily increased in 12 patients. Seven of the 12 showed a negative cumulative water balance and slightly low creatinine clearance. Mean arterial pressure in the other five patients was lower after supplementation and was positively related to sodium excretion. Hypernatremia could not be prevented in the other two patients and they did not survive. Creatinine clearance was below 40 mL/min/m2 in these two patients before supplementation. CONCLUSION: Our protocol worked effectively in patients in whom renal function was preserved. Decreased creatinine clearance because of preexisting dehydration and lower arterial pressure disturbed increase in urinary sodium excretion and temporarily aggravated the hypernatremia.

Blood Volume↗
PubMed2001

[Diffusion-weighted imaging of brain death: study of apparent diffusion coefficient].

DWI(Diffusion-weighted images) of the brain has been revealed to be useful in diagnosis of several clinical conditions. However, little is known about DWI with regard to brain death. We had opportunities to study patients with brain death. Case 1. A 34-year-old woman experienced cardiopulmonary arrest due to severe ventricular fibrillation, and resuscitated after about 120 minutes. After brain death, DWI showed high signals in the cerebral cortex, putamen, thalamus, brain stem and cerebellum, and ADC(apparent diffusion coefficient) values were 30-40% lower than those of normal volunteers. Case 2. A 45-year-old woman experienced cardiopulmonary arrest due to pontine hemorrhage, and was resuscitated after about 20 minutes. Before brain death, DWI showed high signals in the cerebral cortex, putamen, thalamus, brain stem and cerebellum, and ADC values were the same as those of normal volunteers. After brain death, DWI showed more clearly defined in these areas, but ADC values were 30-40% lower than the first values. DWI and ADC mapping shows areas corresponding to edema of a cytotoxic nature and to ischemic tissue. The characteristic views of high signals in the whole area of the brain were present, and an objective evaluation was possible with DWI after the brain death diagnosis by measuring ADC values.

Adult↗
PubMed2000

FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH.

We report that the chromatin-specific transcription elongation factor FACT functions in conjunction with the RNA polymerase II CTD kinase P-TEFb to alleviate transcription inhibition by DSIF (DRB sensitivity-inducing factor) and NELF (negative elongation factor). We find that the kinase activity of TFIIH is dispensable for this activity, demonstrating that TFIIH-mediated CTD phosphorylation is not involved in the regulation of FACT and DSIF/NELF activities. Thus, we propose a novel transcriptional regulatory network in which DSIF/NELF inhibition of transcription is prevented by P-TEFb in cooperation with FACT. This study uncovers a novel role for FACT in the regulation of transcription on naked DNA that is independent of its activities on chromatin templates. In addition, this study reveals functional differences between P-TEFb and TFIIH in the regulation of transcription.

DNA-Binding Proteins↗
PubMed2000

Adult onset Still's disease with hemophagocytic syndrome and severe liver dysfunction.

We report the case of a 55-year-old Japanese woman with adult onset Still's disease in whom hemophagocytic syndrome and severe liver dysfunction developed. High serum levels of ferritin, macrophage colony stimulating factor and interferon-gamma, which imply the presence of hemophagocytic syndrome, were detected. It is known that hemophagocytic syndrome is associated with adult onset Still's disease. In our case, many markedly swollen Kupffer cells with phagocytized red blood cells were found in the liver, as well as macrophages in the bone marrow and spleen. Accordingly, we believe that severe liver dysfunction in this case may have been related to hypercytokinemia due to hemophagocytic syndrome.

Journal Article↗
PubMed2000

Effects of interferon-alpha on peripheral neutrophil counts and serum granulocyte colony-stimulating factor levels in chronic hepatitis C patients.

Granulocytopenia is commonly observed in interferon-alpha (IFN-alpha) therapy. Granulocyte colony-stimulating factor (G-CSF) has been identified as a primary cytokine that regulates neutrophil production, but the kinetics of G-CSF in IFN-alpha-induced granulocytopenia remains unclear. We investigated the effects of IFN-alpha on serum G-CSF levels and peripheral neutrophil counts (NC) in 15 chronic hepatitis C patients treated with standard-dose (10 MU) recombinant IFN-alpha for 24 weeks by using a chemiluminescent enzyme immunoassay for G-CSF. The time course of change after a single IFN-alpha injection showed that mean serum G-CSF levels and NC increased significantly compared with pretreatment values (p < 0.05), and were statistically correlated (r = 0.914, p = 0.0015). On repeating IFN-alpha administration, this change gradually became unclear, and granulocytopenia occurred, accompanied by a significant increase in serum G-CSF (p < 0.01). Both values reached a plateau within 2 weeks after starting treatment, and recovered rapidly after the cessation of therapy. Although continuous administration of IFN-alpha caused a time-dependent granulocytopenia, our results suggest that a single injection of IFN-alpha would be a potent inducer of G-CSF and NC in vivo as a short-term effect and that there would be negative-feedback regulation between them during long-term IFN-alpha therapy.

Adjuvants, Immunologic↗
PubMed2000

Intravenous detergent poisoning.

CASE REPORT: In the literature regarding surfactant poisoning, the route of exposure has almost always been oral. We report a case in which about 40 mL of bath detergent for home use was self-injected. The primary pathophysiologic effects were relative hypovolemia and cardiac dysfunction. The patient experienced frequent ventricular tachycardia, acute renal failure, rhabdomyolysis, hemolysis, and coagulation dysfunction. Intensive care included the administration of antiarrythmial agents and hemodialysis. The patient survived and was discharged from our hospital without sequelae.

Acute Kidney Injury↗