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Biomedical subjects

Y Imamura

Publications and source records attributed to Y Imamura.

At least 19 recordsLinked to original sources
PubMed2003

Possible involvement of Rap1 and Ras in glutamatergic synaptic transmission.

Rap1A, first identified as a suppressor of transformed phenotype induced by an activated ras oncogene, is abundantly expressed in the brain. Its neurophysiological function, however, is poorly understood. When an activated Rap1A mutant (Rap1-12V) or a dominant negative H-Ras mutant (Ras-17N) was expressed in CA1 neurons in cultured hippocampal slices using the sindbis virus-mediated gene transfer technique, NMDA receptor current in response to Schaffer collateral stimulation was suppressed. Expression of activated H-Ras mutant (Ras-12V) resulted in the elevation of both NMDA receptor current and AMPA receptor current. These results implicate counteracting functions of Ras and Rap1 in the regulation of NMDA receptor-mediated synaptic transmission and a positive regulatory role of Ras in AMPA receptor-mediated synaptic transmission.

Animals↗
PubMed2003

Evidence for unconventional strong-coupling superconductivity in PrOs4Sb12: an Sb nuclear quadrupole resonance study.

We report Sb-NQR results which evidence a heavy-fermion (HF) behavior and an unconventional superconducting (SC) property in Pr(Os4Sb12 with T(c)=1.85 K. The temperature (T) dependence of nuclear-spin-lattice-relaxation rate, 1/T(1), and NQR frequency unravel a low-lying crystal-electric-field splitting below T0 approximately 10 K, associated with Pr3+(4f(2))-derived ground state. In the SC state, 1/T(1) shows neither a coherence peak just below T(c) K nor a T3-like power-law behavior observed for anisotropic HF superconductors with the line-node gap. The isotropic energy gap with its size Delta/k(B)=4.8 K seems to open up across T(c) below T(*) approximately 2.3 K. It is surprising that Pr(Os4Sb12 looks like an isotropic HF superconductor-it may indeed argue for Cooper pairing via quadrupolar fluctuations.

Journal Article↗
PubMed2003

Ser624 of the PA subunit of influenza A virus is not essential for viral growth in cells and mice, but required for the maximal viral growth.

Serine at position 624 of PA subunit of the Influenza A virus RNA polymerase is the active site of a serine protease domain. To examine the role of this protease activity in the viral infection cycle, we compared the growth and the pathogenesis of influenza A/WSN/33 (WSN) and the virus encoding a PA with a S624A mutation (S624A virus), which were generated by the plasmid-based rescue system. The growth of S624A virus was less extensive than that of WSN in cells. The LD50 of S624A virus and WSN for intranasal infection in Balb/C mice was 4.0 x 10(4) and 9.3 x 10(3) PFU, respectively. That for intracranial infection was 460 and 200 PFU, respectively. These data indicated that Ser624, the active site of the serine protease activity of PA, is not essential for viral growth and pathogenesis, but is required for the maximal viral growth.

Animals↗
PubMed2003

Feasibility study using a new small electronic pancreatoscope: description of findings in chronic pancreatitis.

BACKGROUND AND STUDY AIMS: Numerous images characteristic of chronic pancreatitis have been obtained with fiberoptic peroral pancreatoscopy systems. However, the resolution of these images is inferior to that obtained with peroral electronic pancreatoscopy (PEPS). Clearer images of the pancreatic duct with chronic pancreatitis have now been documented, in some cases using PEPS alone. The significance of this finding is reported here. PATIENTS AND METHODS: A total of 42 PEPS procedures were carried out in 36 patients with chronic pancreatitis, without sphincterotomy or balloon dilation of the papilla of Vater. Using endoscopic retrograde pancreatography, the patients were classified as having equivocal (n=5), mild (n=5), moderate (n=15), or marked (n=11) degrees of chronic pancreatitis. The insertion rate with PEPS was 90 % (38 of 42 procedures), and it was ultimately possible to examine five, three, 13, and 11 patients in each group, respectively. RESULTS: Images of turbid pancreatic juice, protein plugs of various shapes, pancreatic calculi, indistinct vascular markings, whitish mucosa, local redness, scattered redness, disappearance of the fold, deformation of the fold, irregularly dilated lumen, and stenosis were found to be characteristic of chronic pancreatitis. These images were obtained using PEPS. CONCLUSIONS: PEPS proved to be a feasible new technique for diagnosing chronic pancreatitis, and it was able to detect abnormal findings more clearly than other imaging methods.

Aged↗
PubMed2003

Use of perfluorocarbon liquid during vitrectomy for severe proliferative diabetic retinopathy.

AIM: To evaluate the value of using perfluorocarbon liquid (PFCL) during vitrectomy in eyes with proliferative diabetic retinopathy (PDR). METHODS: The surgical records of eyes with PDR (291 eyes of 228 patients) that underwent vitrectomy in the vitreoretinal service of Osaka Medical College (April 1999 to October 2001) were reviewed. From these, 18 eyes of 15 patients had PFCL used during vitrectomy, and the preoperative and postoperative findings of these eyes were analysed. RESULTS: All of the 18 eyes had advanced PDR with tractional and/or rhegmatogenous retinal detachment. PFCL enabled easier flattening of the retinal folds and effective endophotocoagulation. In two cases, PFCL was used to flatten a bullous retinal detachment that developed when a tight vitreoretinal adhesion was loosened. In two other cases with combined traction/rhegmatogenous retinal detachment, PFCL was used to tamponade the detached retina which then allowed successful membrane dissection. Anatomical success was obtained in 16 of the 18 cases (mean follow up time 13.3 months) with visual acuity of 20/200 or better in nine eyes (50%). CONCLUSIONS: PFCL is considered to be a useful adjunct during vitrectomy for the treatment of severe PDR.

Adult↗
PubMed2003

Detection of cancer clones in human gastric adenoma by increased DNA-instability and other biomarkers.

An immunohistochemical differential staining of cancerous cells with anti-cytidine antibody after denaturation of nuclear DNA by acid hydrolysis with 2N HCl at 30 degree C for 20 min (DNA-instability test) has been used as a marker of malignancy. The test was applied to bioptic tissues of human gastric polyp assessed histopathologically as foveolar hyperplastic polyp (13 cases), mild (58 cases), moderate (86 cases), and severe (20 cases) dysplasia, and adenocarcinomas (14 cases). The serial sections of the same tissues were also subjected to immunohistochemical staining for Ki67, p53, DNA-fragmentation factor (DFF45), and basic fibroblast growth factor (bFGF). The DNA-instability test was positive in 14 (100%) adenocarcinoma cases, 20 (100%) severe dysplasia cases, 52 (60.5%) moderate dysplasia cases, and 12 (20.7%) mild dysplasia cases, indicating malignancy. All foveolar hyperplastic polyps were negative to the DNA-instability testing. Furthermore, the percentage of glands positive in the DNA-instability test steadily increased in going from mild (10%), to moderate (40%), to severe (100%) dysplasia, and adenocarcinoma (100%). All other biological markers tested in the present study showed significantly higher values in the adenoma glands, being positive to DNA-instability testing, irrespective of the dysplasia grade, as compared to those in the adenoma glands that were negative to DNA-instability testing. Furthermore, the former values were comparable to those in adenocarcinoma. These results indicate that cancer cell clones are already present at the adenoma stages showing a positive DNA-instability test, enhanced proliferative activity, p53 mutation, induction of DFF45 and bFGF. These factors allow cancer cell proliferation, producing heterogeneous subclones due to DNA-instability, enhancing their survival by escaping apoptosis, and providing abundant nutrients during the early-stage progression of gastric cancer. Based on these findings, we herein propose the concept of "procancer" (as opposed to "pre-cancer") as being a unique stage during the course of carcinogenesis and cancer progression. We designate the term to cancer clones at the very early stages of malignant progression that do not show distinguishable morphological atypia but do show positive DNA-instability testing and positive staining for various biomarkers such as Ki67, p53, DFF45, and bFGF. We also define the abnormal positive staining of these biomarkers, including the DNA-instability test as "functional atypia", compared to the ordinary morphological atypia.

Adenocarcinoma↗
PubMed2002

Cefepime or carbapenem treatment for febrile neutropenia as a single agent is as effective as a combination of 4th-generation cephalosporin + aminoglycosides: comparative study.

1998, a consensus meeting was held in Miyazaki, Japan, to develop an approach to management of febrile neutropenia (FN). The K-HOT study group decided to examine whether this proposal was applicable to clinical practice in a multicenter study. Patients who developed fever with neutrophil counts <1,000/microL were randomized to receive either a single antibiotic, cefepime or one of the carbapenems, or a combination of cefepime and an aminoglycoside. Patients who became afebrile within the first 3 days were continued on the same treatment. Patients who remained febrile were switched to a combination regimen if they were randomized to receive a single agent, and patients on combination medication were changed from cefepime to another cephalosporin. A total of 165 patients were entered into the trial. One hundred fifty-three patients were evaluable for response. The average age was 52 years, and 70% of the patients had acute leukemia. Severe neutropenia, defined as <100/microL at the time of FN, was seen in 62% of the patients on entry and during the course of treatment 71% of patients experienced neutrophil counts of <100/microL. Microbiologically documented infection was seen in 6.5% for monotherapy, and 10.5% for a combination treatment, and fever of unknown origin occurred in 75.3% and 59.2% of the patients in each regimen, respectively. Excellent to good response was seen in two-thirds of the patients in all treatment groups. Adverse events were minimal, and three early deaths were observed at days 9, 16, and 16 among patients treated with a single antibiotic and three in the combination regimen group at days 14, 15, and 20. These results indicate that cefepime or a carbapenem alone is as effective as a combination of cefepime and an aminoglycoside for treating FN.

Adult↗
PubMed2002

Differential hormonal regulation of carbonyl reductase activities in liver and kidney microsomes of rat.

1. In the male rat, hepatic microsomal carbonyl reductase (CR) activity decreased by testectomy (Tx) was restored to the control level by the treatment with testosterone propionate (TP), even though the enzyme activity decreased by hypophysectomy (Hx) was not increased by the treatment with TP. On the other hand, renal microsomal CR activities decreased by Tx and Hx were markedly increased by the treatment with TP. 2. The treatment with TP had no effect on the CR activity in liver microsomes of the ovariectomized or hypophysectomized female rat. On the other hand, the CR activities in kidney microsomes of the ovariectomized and hypophysectomized female rat were significantly increased by the treatment with TP. 3. The results indicate that in rat programmed by neonatal androgens, the hepatic microsomal CR activity is regulated indirectly by androgens through the hypothalamus-pituitary system, whereas the hormonal regulation of the renal microsomal CR activity is not via the pituitary. We conclude that the regulatory mechanism of the CR activity in liver microsomes is distinguishable from that in kidney microsomes.

Alcohol Oxidoreductases↗
PubMed2001

The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis.

Matrix metalloproteinases (MMPs) are essential for proper extracellular matrix remodeling. We previously found that a membrane-anchored glycoprotein, RECK, negatively regulates MMP-9 and inhibits tumor invasion and metastasis. Here we show that RECK regulates two other MMPs, MMP-2 and MT1-MMP, known to be involved in cancer progression, that mice lacking a functional RECK gene die around E10.5 with defects in collagen fibrils, the basal lamina, and vascular development, and that this phenotype is partially suppressed by MMP-2 null mutation. Also, vascular sprouting is dramatically suppressed in tumors derived from RECK-expressing fibrosarcoma cells grown in nude mice. These results support a role for RECK in the regulation of MMP-2 in vivo and implicate RECK downregulation in tumor angiogenesis.

Animals↗
PubMed2001

Hypoglycemic effect of S(-)-hydroxyhexamide, a major metabolite of acetohexamide, and its enantiomer R(+)-hydroxyhexamide.

A short-lasting hypoglycemic effect was observed when S(-)-hydroxyhexamide (S-HH), a major metabolite of acetohexamide, and its enantiomer R(+)-hydroxyhexamide (R-HH), were administered orally to rats. Since the reductive metabolism of acetohexamide is known to be reversible in rats, oral administration of R-HH may exhibit the hypoglycemic effect through the generation of acetohexamide. However, oral administration of R-HH to rabbits, in spite of their inability to oxidize R-HH to acetohexamide, caused a significant decrease and increase, respectively, of plasma glucose and insulin levels. Furthermore, both S-HH and R-HH were found to stimulate the secretion of insulin from hamster HIT T15 cells (pancreatic beta-cells). These results provide further evidence that both R-HH and S-HH exhibit a significant hypoglycemic effect.

Acetohexamide↗
PubMed2001

Gut transit time after ileal pouch-anal anastomosis using a radiopaque marker.

PURPOSE: The aim of this study was to determine the contribution of gastrointestinal motility to bowel function and the pathogenesis of pouchitis after ileal pouch-anal anastomosis. METHODS: Gastrointestinal transit time was assessed by a radiopaque marker technique in 32 patients with ulcerative colitis. RESULTS: Small intestinal transit time and pouch emptying time were 4.1 +/- 2 hours and 4.1 +/- 2.5 hours, respectively. There was no significant difference in pouch emptying time between patients with and without pouchitis. When only patients with acute pouchitis that responded to metronidazole were analyzed, there was a trend toward a prolonged pouch emptying time compared with those without pouchitis (P = 0.095). Whole gut transit time was inversely correlated with 24-hour stool frequency in patients without pouchitis (r = -0.63, P < 0.005). In the analysis of regional transit time, only small intestinal transit time was inversely correlated with 24-hour stool frequency (r = -0.472, P < 0.05). Significant prolongation of small intestinal transit time was demonstrated in patients over a period of 41 months (the median time) after ileostomy closure compared with those whose pouches had been functioning for 6 to 41 months (5.4 +/- 1.7 hours vs. 3.1 +/- 1.3 hours, P < 0.005). CONCLUSIONS: There was an association between small intestinal motility and bowel frequency. Further investigation is necessary in the pathogenesis of acute pouchitis regarding the relationship between delayed pouch emptying and subsequent development of mucosal inflammation.

Adolescent↗
PubMed2001

Viability of liver grafts from fasted donor rats: relationship to sinusoidal endothelial cell apoptosis.

Previous studies have shown that livers from fasted donors appear to tolerate long-term preservation better than livers from fed donors, but the mechanism is not clear. Some studies have shown that the apoptosis of sinusoidal endothelial cells (SEC) appeared to be a pivotal mechanism of ischemia/reperfusion injury in liver transplantation. The purpose of the present investigation was to evaluate the relation of SEC apoptosis to liver viability in rats after liver transplantation, comparing findings for fasted and fed donors. Wistar rats were used as donors and recipients. The fed group had access to solid feed and water ad libitum. The fasted group was allowed access only to water for 4 days prior to liver harvest. All rat livers were preserved with University of Wisconsin (UW) solution at 2 degrees C for 24 h. After preservation, the livers were orthotopically transplanted, and survival time was measured. Apoptosis was determined by in-situ staining for apoptotic cells, using a TdT-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay and electron microscope (EM) examination separately. The 14-day survival rates after 24-h preservation were 0% (0/11) for recipients of livers from fed donors and 91% (10/11) for recipients of livers from fasted donors. There was no significant difference in the numbers of TUNEL-positive SEC after 24-h preservation between the two groups. However, at 6 h after transplantation, the number of TUNEL-positive SEC was significantly higher in the fed group than in the fasted group. These results suggest that donor fasting decreases SEC apoptosis after reperfusion alone, and that this may be related to the protection of the liver graft from reperfusion injury.

Analysis of Variance↗
PubMed2001

Kupffer cell function in ischemic and nonischemic livers after hepatic partial ischemia/reperfusion.

Hepatic partial ischemic/reperfusion (I/R) injury, in which ischemic and nonischemic areas of the liver are likely to respond to each other after reperfusion, often occurs following hepatobiliary surgical procedures. Kupffer cells (KCs) are considered to play a major role in hepatic I/R injury. To study the activation of KCs in ischemic and nonischemic liver tissues following hepatic I/R, we investigated the superoxide generation and proinflammatory cytokine production of KCs in both liver parts in a rat model of partial hepatic I/R injury. KC superoxide generation in the ischemic and nonischemic lobes was upregulated 6 and 24 h after reperfusion, respectively, and then accelerated. The production of interleukin-1beta (IL-1beta) by KCs in the ischemic lobes increased during the early and late phases, 6 h and 48-72 h after reperfusion, respectively. A late increase in IL-1beta production was also observed in the nonischemic lobes. Production of tumor necrosis factor-alpha (TNF-alpha) increased 6-24h after reperfusion in both lobes. Upregulation of IL-1beta mRNA in the ischemic lobes preceded the upregulation of TNF-alpha mRNA in both lobes. The hepatic partial I/R process results in activation of KCs in ischemic and nonischemic areas of the liver. The KCs are activated during the early phase after reperfusion in the ischemic areas, followed by activation in both the ischemic and nonischemic areas. This could be a cause of liver dysfunction after partial hepatic I/R during surgery.

Animals↗
PubMed2001

Gastric signet ring cell adenocarcinoma metastatic to the iris.

PURPOSE: To report a case of gastric signet ring cell adenocarcinoma metastatic to the iris. METHODS: Case report. A 38-year-old man with a history of gastric signet ring cell adenocarcinoma presented with a white lacework-like mass on the iris of the left eye. RESULTS: Systemic medical evaluation demonstrated no other metastasis. Because of increased intraocular pressure, trabeculectomy and peripheral iridectomy were performed. Histology of the iris specimen demonstrated metastasis of gastric signet ring cell adenocarcinoma to the iris. CONCLUSION: Gastric signet ring cell carcinoma can metastasize to the iris. Ophthalmologists should include this possibility in the differential diagnosis when encountering a patient with a history of gastric adenocarcinoma and an iris mass.

Adult↗
PubMed2001

Paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level as possible risk factors for exudative age-related macular degeneration.

PURPOSE: Paraoxonase (E.C.3.1.1.2) is a polymorphic protein shown to prevent low-density lipoprotein oxidation. Our purpose is to evaluate the hypothesis that paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level play a role in the occurrence of exudative age-related macular degeneration. METHODS: We analyzed paraoxonase genotypes (A/B, Gln-Arg192 and L/M, Leu-Met54) and plasma oxidized low-density lipoprotein levels in 72 unrelated Japanese patients with exudative age-related macular degeneration and compared the results with those of 140 age-matched and sex-matched control subjects. RESULTS: The distribution of paraoxonase 192 and paraoxonase 54 polymorphisms was significantly different between the patients with age-related macular degeneration and control subjects (chi-square = 6.226, P =.0445, and chi-square = 6.863, P =.0323, respectively). The high frequency of the BB genotype at position 192 was observed in the exudative age-related macular degeneration group compared with control subjects (52.8% vs 35.0%, respectively; P =.0127). The high frequency of the LL genotype at position 54 was observed in the patients more than the controls (91.7% vs 77.1%, respectively; P =.0090). The mean (+/- SE) oxidized low-density lipoprotein levels in the patients was significantly higher than in the controls (19.1 +/- 1.0 vs 16.2 +/- 0.6 U/ml, P <.01). CONCLUSION: These results indicate that the paraoxonase gene polymorphisms may represent a possible genetic risk factor for age-related macular degeneration and that increased plasma oxidized low-density lipoprotein may be involved in the pathogenesis of age-related macular degeneration.

Aged↗