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Biomedical subjects

Y Fujii

Publications and source records attributed to Y Fujii.

At least 307 records · Page 17Linked to original sources
PubMed1999

DNA methylation analysis at distal and proximal promoter regions of the oestrogen receptor gene in breast cancers.

Oestrogen receptor alpha (ER-alpha) gene has two specific promoters, distal (P0) and proximal (P1), which induce almost identical transcripts in size due to different splicing. We examined the methylation at both promoter regions of the ER-alpha gene using HpaII, a methylation-sensitive restriction enzyme, prior to polymerase chain reaction (PCR) amplification. To confirm the results of PCR-based methylation analysis, Southern hybridization was also performed. Twenty of 29 patients with ER-alpha-positive tumours and five of 27 with ER-alpha-negative tumours were unmethylated at the P1 promoter region of the ER-alpha gene. The incidence of methylation was highly negatively correlated with ER-alpha expression (P = 0.0002). A similarly negative correlation was observed at the P0 promoter region of the ER-alpha gene (P = 0.0154). Additionally, the tumours with the ER-alpha gene hypermethylated at both promoter regions had definitely negative ER-alpha values. It was suggested that this epigenetic change might control ER-alpha expression, and might play an important role in the loss of hormone-dependence in breast cancer.

Breast Neoplasms↗
PubMed1999

Relationship between stimulating current and accelographic train-of-four response at the great toe.

We investigated the accelographic train-of-four response evaluated at the great toe at varying stimulating currents. Fifteen adult patients undergoing elective general anaesthesia were studied. The mean current at which a supramaximal T1 value could be elicited was > 49 (9) mA [mean (SD)]. Ratios of accelographic T1 values at 50, 40, 30, 20 and 10 mA to accelographic T1 value at 60 mA were 0.90 (0. 18), 0.58 (0.37), 0.38 (0.37), 0.19 (0.26) and 0.00 (0.00), respectively [mean (SD), p < 0.05 for 50 mA vs. 30, 20 and 10 mA, p < 0.05 for 40 mA vs. 20 and 10 mA, and p < 0.05 for 30 vs. 10 mA]. Threshold currents for train-of-four (the lowest currents at which any train-of-four response could be elicited) before and after induction of anaesthesia were 30 (10) and 31 (10) mA, respectively. The train-of-four ratio (T4/T1) measured at varying currents did not differ significantly. However, in the patients in whom threshold currents for train-of-four were 40, 30 and 20 mA, the train-of-four ratio recorded at the threshold current was significantly less than at 50 mA. We conclude that at the great toe, the mean current at which a supramaximal response to train-of-four can be yielded is as high as > 49 mA. The mean threshold currents for TOF before and after induction of anaesthesia were 30 and 31 mA, respectively. Train-of-four ratio measured at the threshold current is less than that at 50 mA.

Anesthesia, General↗
PubMed1999

Granisetron reduces post-operative vomiting in children: a dose-ranging study.

This study was undertaken to determine the minimum effective dose of granisetron, 5-hydroxytryptamine type 3 receptor antagonist, for the prevention of post-operative vomiting in children undergoing general inhalational anaesthesia for surgery (inguinal hernia and phimosis). In a randomized, double-blind manner, 120 children, ASA physical status I, aged 4-10 years, were assigned to receive placebo (saline) or granisetron at three different doses (20 micrograms kg-1, 40 micrograms kg-1, 100 micrograms kg-1) intravenously immediately after inhalation induction of anaesthesia (n = 30 of each). A complete response, defined as no emesis and no need for another rescue antiemetic during the first 24 h after anaesthesia, occurred in 57% with placebo, 67% with granisetron 20 micrograms kg-1, 90% with granisetron 40 micrograms kg-1 and 90% with granisetron 100 micrograms kg-1 respectively (P < 0.05; overall Fisher's exact probability test). No clinically important adverse events were observed in any of the groups. Our results suggest that granisetron 40 micrograms kg-1 is the minimum effective dose for the prevention of emesis after paediatric surgery, and that increasing its dose to 100 micrograms kg-1 provides no demonstrable benefit.

Anesthesia, Inhalation↗
PubMed1999

Anti-emetic efficacy of prophylactic granisetron compared with perphenazine for the prevention of post-operative vomiting in children.

We have compared the efficacy of granisetron with perphenazine in the prevention of vomiting after tonsillectomy with or without adenoidectomy in children. In a prospective, randomized, double-blind study, 90 paediatric patients, ASA I, aged 4-10 years, received granisetron 40 mg kg-1 or perphenazine 70 mg kg-1 (n = 45 each) intravenously immediately after an inhalation induction of anaesthesia. A standard general anaesthetic technique was employed throughout. A complete response, defined as no emesis with no need for another rescue antiemetic, during the first 3 h (0-3 h) after anesthesia was 87% with granisetron and 78% with perphenazine (P = 0.204). The corresponding incidence during the next 21 h (3-24 h) after anaesthesia was 87% and 62% (P = 0.007). No clinically serious adverse events were observed in any of the groups. We conclude that granisetron is a better anti-emetic than perphenazine for the long-term prevention of post-operative vomiting in children undergoing general anaesthesia for tonsillectomy.

Adenoidectomy↗
PubMed1999

Prophylactic therapy with combined granisetron and dexamethasone for the prevention of post-operative vomiting in children.

This study was undertaken to compare the efficacy and safety of granisetron, a 5-hydroxytryptamine type 3 receptor antagonist, and dexamethasone and each drug alone for the prevention of post-operative vomiting by children, with no history of motion sickness and/or previous post-operative vomiting, undergoing general inhalational anaesthesia for surgery (inguinal hernia and phimosis). In a randomized, double-blind manner, 150 children, ASA physical status 1, aged 4-10 years, were assigned to receive granisetron 40 mg kg-1, dexamethasone 150 mg kg-1, or granisetron 40 mg kg-1 plus dexamethasone 150 mg kg-1 intravenously immediately after inhalation induction of anaesthesia (n = 50 of each). A complete response, defined as no emesis and no need for another rescue anti-emetic during the first 24 h after anaesthesia, was 86% with granisetron, 68% with dexamethasone and 98% with granisetron plus dexamethasone, respectively (P < 0.05; overall Fisher's exact probability test). No clinically serious adverse events were observed in any of the groups. In conclusion, prophylactic therapy with combined granisetron and dexamethasone was more effective than was each anti-emetic alone for the prevention of vomiting after paediatric surgery.

Anesthesia, Inhalation↗
PubMed1999

Milrinone enhances the contractility of fatigued diaphragm in dogs: a dose-ranging study.

The dose-related effects of milrinone, a phosphodiesterase (PDE) III inhibitor, on the contractility of fatigued diaphragm were studied in dogs. Animals were divided into three groups of eight each. Diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. After the production of fatigue, Group I received no study drug; Group II was infused with milrinone (50 mg kg-1 loading dose plus 0.2 mg kg-1 min-1 maintenance dose); Group III was infused with milrinone (50 mg kg-1 loading dose plus 0.5 mg kg-1 min-1 maintenance dose). Diaphragmatic contractility was assessed by measurement of transdiaphragmatic pressure. After the fatigue-producing period, transdiaphragmatic pressure at low-frequency stimulation (20-Hz) decreased from the prefatigued values in all groups (P < 0.05), whereas transdiaphragmatic pressure at high-frequency (100-Hz) stimulation did not change. Compared with Group I, transdiaphragmatic pressure to each stimulus increased during milrinone infusion in Groups II and III (P < 0.05). The increase in trans-diaphragmatic pressure was greater in Group III than in Group II (P < 0.05). It is concluded that milrinone is associated with a dose-related effect on the contractility of fatigued diaphragm in dogs.

Animals↗
PubMed1999

Prevention of post-operative nausea and vomiting with combined granisetron and droperidol in women undergoing thyroidectomy.

We have compared the efficacy and safety of combined granisetron and droperidol with each anti-emetic alone for preventing post-operative nausea and vomiting after thyroidectomy. In a prospective, randomized, double-blind study, 180 women received granisetron 40 micrograms kg-1, droperidol 20 micrograms kg-1, or granisetron 40 micrograms kg-1 plus droperidol 20 micrograms kg-1 (n = 60 of each) intravenously immediately before induction of anaesthesia. A standard general anaesthetic technique and post-operative analgesia were used. A complete response, defined as no post-operative nausea and vomiting and no need for another rescue anti-emetic, during the first 24 h after anaesthesia occurred in 88%, 60% and 98% of patients who had received granisetron, droperidol and granisetron plus droperidol (P < 0.05; overall Fisher's exact probability test). No clinically important adverse events due to the drugs were observed in any of the groups. In summary, prophylactic use of combined granisetron and droperidol is more effective than each drug alone for the prevention of post-operative nausea and vomiting in female patients undergoing thyroidectomy.

Adult↗
PubMed1999

Depletion of Escherichia coli 4.5S RNA leads to an increase in the amount of protein elongation factor EF-G associated with ribosomes.

In Escherichia coli, 4.5S RNA is found in complexes with both protein translocation protein, Ffh (a bacterial homolog of mammalian SRP54) and protein synthesis elongation factor G (EF-G). To analyze the function of 4.5S RNA in translation, we initially assessed the sensitivity of the association of 4.5S RNA with the ribosome after treatment with antibiotics that affect various stages of protein synthesis. Fusidic acid and viomycin caused 4.5S RNA to cosediment with the 70S ribosomal fraction, indicating that 4.5S RNA enters the ribosome before ribosomal translocation and release of EF-G-GDP from the ribosome. On the other hand, depletion of 4.5S RNA led to the retention of a significant amount of EF-G on 70S ribosomes. In addition, 4.5S RNA shares a conserved decanucleotide sequence (58GAAGCAGCCA67) motif with the characterized EF-G-binding site at positions 1068-1077 on 23S RNA. We therefore examined by gel mobility-shift assay whether or not mutations in the domain-IV region of 4.5S RNA, including this conserved motif, disturb the binding of EF-G to 23S RNA. Any mutation at the C62, G64 or A67 residues within this motif abolished competition activity. Therefore, we propose that 4.5S RNA is concerned with the mode of association of EF-G with the ribosomes. Moreover, this function depends on the secondary structure of 4.5S RNA as well as a ten-base sequence conserved between the two RNAs.

Bacterial Proteins↗
PubMed1999

Characterization of a truncated recombinant form of human membrane type 3 matrix metalloproteinase.

Membrane type 3 matrix metalloproteinase (MT3-MMP), an activator for the zymogen of MMP-2 (proMMP-2, or progelatinase A), is known to be expressed in human placenta, brain, lung and rat vascular smooth muscle cells, but information about its biochemical properties is limited. In the present study, we expressed and purified a truncated form of MT3-MMP lacking the transmembrane and intracytoplasmic domain (DeltaMT3) and characterized the enzyme biochemically. DeltaMT3 digested type III collagen into characteristic 3/4- and 1/4-fragments by cleaving the Gly781-Ile782 and Gly784-Ile785 bonds of alpha1(III) chains. Although DeltaMT3 did not have such an activity against type I collagen, it attacked the Gly4-Ile5 bond of the triple helical portion of alpha2(I) chains, leading to removal of the crosslink containing N-terminal telopeptides. By quantitative analyses of the activities of DeltaMT3 and a similar deletion mutant of MT1-MMP (DeltaMT1), DeltaMT3 was approximately fivefold more efficient at cleaving type III collagen. DeltaMT3 also digested cartilage proteoglycan, gelatin, fibronectin, vitronectin, laminin-1, alpha1-proteinase inhibitor and alpha2-macroglobulin into almost identical fragments to those given by DeltaMT1, although carboxymethylated transferrin digestion by DeltaMT3 generated some extra fragments. The activity of DeltaMT3 was inhibited by tissue inhibitor of metalloproteinases-2 (TIMP-2) and TIMP-3 in a 1 : 1 stoichiometry, but not by TIMP-1. ProMMP-2 was partially activated by DeltaMT3 to give the intermediate form. These results indicate that, like MT1-MMP, MT3-MMP exhibits proteolytic activities against a wide range of extracellular matrix molecules. However, differences in the proMMP-2 activation and tissue distribution suggest that MT3-MMP and MT1-MMP play different roles in the pathophysiological digestion of extracellular matrix.

Collagen↗
PubMed1999

Possible misinterpretation on computed tomography of left inferior vena cava as retroperitoneal lymph node metastasis: a report of two cases.

PURPOSE: We report on two cases of retroperitoneal lymph node metastasis of testicular cancer with left inferior vena cava. METHODS/RESULTS: A 25-year-old man with a left testicular cancer with pulmonary and retroperitoneal lymph node metastases received three courses of VIP (etoposide, ifosfamide and cisplatinum) chemotherapy. Subsequent abdominal computed tomography (CT) revealed round lesions enhanced with contrast agent on both sides of the aorta inside the degenerated lymphadenopathy. These lesions were regarded as a duplicated inferior vena cava (IVC) and this was confirmed at retroperitoneal lymph node dissection. The second case is of a 21-year-old man with a left testicular cancer with pulmonary, liver and widespread lymph node metastases. Subsequent to a course of VIP chemotherapy, super high-dose chemotherapy was administered. Abdominal CT revealed a round mass enhanced with contrast agent on the left side of the aorta adjacent to the degenerated lymphadenopathy, which was regarded as the transposed left IVC and this was confirmed at lymph node dissection. CONCLUSIONS: In both cases, initial CT failed to detect the lesions as the left IVC and there was a possibility for the misinterpretation of such venous anomalies with residual lymphadenopathy.

Adult↗
PubMed1999

Combination of granisetron and droperidol for the prevention of vomiting after paediatric strabismus surgery.

This study was undertaken to compare the efficacy of granisetron plus droperidol with each antiemetic alone for the prevention of vomiting after paediatric strabismus surgery. In a prospective, randomized, double-blinded trial, 120 ASA physical status I children, aged 4-10 years, received granisetron 40 microg.kg- 1, droperidol 50 microg.kg- 1, granisetron 40 microg.kg- 1 plus droperidol 50 microg.kg- 1 (n=40 of each) intravenously after an inhalation induction of anaesthesia. A complete response, defined as no vomiting, no retching and no need for another rescue antiemetic medication, during 0-3 h after anaesthesia was 80% with granisetron, 45% with droperidol and 98% with granisetron plus droperidol, respectively; the corresponding incidence during 3-24 h after anaesthesia was 78%, 38% and 98% (P< 0.05; overall chi-squared test with Yates continuity correction). No clinically important adverse events were observed in any of the groups. In conclusion, a combination of granisetron and droperidol was more effective than granisetron or droperidol as a sole antiemetic for the prevention of postoperative vomiting in children undergoing strabismus repair.

Analysis of Variance↗
PubMed1999

Prevention of postoperative vomiting with granisetron in paediatric patients with and without a history of motion sickness.

A history of motion sickness is one of the patient-related factors associated with postoperative emesis. This prospective, randomized, double-blind, placebo-controlled study was undertaken to assess the efficacy of granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, for preventing postoperative vomiting after tonsillectomy in 120 children with (n = 60) and without (n = 60) a history of motion sickness. Patients received a single dose of granisetron (40 micrograms.kg-1) or placebo (saline) (n = 30 of each) intravenously after an inhalation induction of anaesthesia. A complete response, defined as no vomiting, no retching and no need for another rescue medication, during the first 24 h after anaesthesia was 77% and 13% in patients with a history of motion sickness who had received granisetron or placebo, respectively; the corresponding incidence was 83% and 40% in those without it (P < 0.05; chi 2 test with Yates' continuity correction). No clinically serious adverse effects due to the study drug were observed in any of the groups. In conclusion, prophylactic antiemetic therapy with granisetron is effective for preventing postoperative emesis in children with a history of motion sickness as well as in those without it.

Antiemetics↗
PubMed1999

Human autoantibodies against HD1/plectin in paraneoplastic pemphigus.

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease that occurs in association with underlying neoplasms. PNP patients develop characteristic autoantibodies directed against multiple antigens, mostly identified as members of the plakin family of cytoplasmic proteins (desmoplakin I and II, bullous pemphigoid antigen I, envoplakin, and periplakin). HD1/plectin, another member of the plakin family, has not previously been detected in the characteristic PNP antigen complex, which may relate to practical difficulties associated with its large size (molecular weight approximately 500 kDa). In this study, a combination of immunoprecipitation and immunoblot is used to demonstrate that HD1/plectin is also recognized by sera from PNP patients. Thirteen of 16 PNP sera tested were positive for HD1/plectin compared with none of 43 control sera (11 pemphigus vulgaris, 11 pemphigus foliaceus, 11 bullous pemphigoid, and 10 normal individuals). Combined with our recent finding that desmoglein 3 and desmoglein 1 are cell surface target antigens in PNP, this demonstration of plectin/HD1 as another component of the antigen complex in PNP confirms that PNP is an autoimmune disease against desmoglein and plakin family molecules.

Autoantibodies↗
PubMed1999

Low density lipoprotein apheresis therapy for steroid-resistant nephrotic syndrome. Kansai-FGS-Apheresis Treatment (K-FLAT) Study Group.

BACKGROUND: The pathogenic role of hyperlipidemia in long-standing nephrotic syndrome (NS) is known to be responsible for both the progression of glomerulosclerosis and tubulointerstitial injury, especially in focal segmental glomerulosclerosis (FGS). METHODS: Aggressive lipid lowering treatment by low density lipoprotein (LDL) apheresis (LDL-A) using a dextran sulfate cellulose column to treat patients with steroid-resistant or frequently recurrent severe NS was performed first without fixing the protocol in eight patients with FGS and one with minimal change nephrotic syndrome (MCNS). The period of NS before LDL-A, number and average intervals of LDL-A until the end of the therapy, and the prognosis were investigated. Next, a multicenter study with a fixed protocol of LDL-A treatment was designed in combination with steroid therapy for treatment twice a week for three weeks and weekly for six weeks, and was performed in 17 patients with FGS. The effects on the state of NS in addition to the change of urinary eicosanoid metabolites and remission rates were evaluated. RESULTS: In the preliminary study, along with a rapid improvement of hyperlipidemia, a high incidence of remission was achieved by LDL-A performed at relatively short intervals. In the multicenter study with a fixed protocol, there was a significant decrease of urinary protein (P < 0.001) and increase of serum albumin (P < 0.02) as well as a decrease of thromboxane B2 (TXB2) excretion (P < 0.05) after the treatment. Urinary excretion of TXB2 was significantly reduced after LDL-A (P < 0.05). The rate of entering into complete or incomplete remission was 71% with a relatively short duration of nephrotic-range proteinuria using the LDL-A therapy in comparison with steroid therapy alone. CONCLUSION: The rapid improvement of hypercholesterolemia with LDL-A treatment may provide a new approach for a high rate of improvement in the degree of NS in steroid-resistant NS of FGS and MCNS.

Adolescent↗
PubMed1999

Helicobacter pylori in the natural environment.

The presence of Helicobacter pylori (H. pylori) in the natural environment has been demonstrated in a number of studies. However, its route of infection into humans is unknown. To study this further, we attempted to detect H. pylori in the natural environment in a region of Japan with a high infection rate. Tap and well water and field soil samples were collected from around the residences of subjects who had participated in an epidemiological survey in 1996. Samples of water from rivers and ponds, and specimens of flies and cow faeces were collected in the region. DNA was extracted from the water, field soil and faecal samples after selective collection of H. pylori by the immunomagnetic-bead separation technique. H. pylori-specific DNA was detected in water, field soil, flies and cow faeces by nested polymerase chain reaction (PCR), and the ureA partial sequences of the PCR products were aligned. The nucleotide sequences of the samples amplified by PCR were highly homologous (96-100%) with the H. pylori sequence in the GenBank database and the H. pylori-specific DNA sequences were highly homologous with each other. These findings suggest the existence of H. pylori in the natural environment and a possible transmission route.

Animals↗
PubMed1999

Hydrogen peroxide-induced apoptosis in HL-60 cells requires caspase-3 activation.

Apoptosis has been associated with oxidative stress in biological systems. Caspases have been considered to play a pivotal role in the execution phase of apoptosis. However, which caspases function as executioners in reactive oxygen species (ROS)-induced apoptosis is not known. The present study was performed to identify the major caspases acting in ROS-induced apoptosis. Treatment of HL-60 cells with 50 microM hydrogen peroxide (H2O2) for 4 h induced the morphological changes such as condensed and/or fragmented nuclei, increase in caspase-3 subfamily protease activities, reduction of the procaspase-3 and a DNA fragmentation. To determine the role of caspases in H2O2-induced apoptosis, caspase inhibitors, acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-cmk), acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO) and acetyl-Val-Glu-Ile-Asp-aldehyde (Ac-VEID-CHO), selective for caspase-1 subfamily, caspase-3 subfamily and caspase-6, respectively, were loaded into the cells using an osmotic lysis of pinosomes method. Of these caspase inhibitors, only Ac-DEVD-CHO completely blocked morphological changes, caspase-3 subfamily protease activation and DNA ladder formation in H2O2-treated HL-60 cells. This inhibitory effect was dose-dependent. These results suggest that caspase-3, but not caspase-1 is required for commitment to ROS-triggered apoptosis.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Electromyographic assessment of neuromuscular block at the gastrocnemius muscle.

We have assessed neuromuscular block electromyographically at the gastrocnemius muscle and compared it with that at the abductor digiti minimi muscle in 60 adult patients undergoing cervical spine surgery under general anaesthesia. All patients were in the prone position. After vecuronium 0.2 mg kg-1, times to onset of neuromuscular block at the gastrocnemius and abductor digiti minimi muscles were mean 147 (SD 24) and 145 (14) s, respectively (ns). Times to return of the first response of the post-tetanic count (PTC1) at the gastrocnemius and abductor digiti minimi muscles were 27.7 (5.6) and 37.0 (5.9) min, respectively (P = 0.0001). Times to return of the first response of the train-of-four (TOF) at the gastrocnemius and abductor digiti minimi muscles were 41.0 (9.1) and 49.9 (8.7) min, respectively (P = 0.01). Recovery of PTC, T1/T0 and TOF ratio at the gastrocnemius muscle were significantly faster than at the abductor digiti minimi muscle.

Adult↗