Studies on the multidrug resistance gene expression in the livers of rats associated with different susceptibility of hepatocarcinogenesis

Inbred carcinogen-resistant DRH rat strain developed from the closed colony Donryu rats on the basis of selective markers such as poor induction of gamma-glutamyltranspeptidase and marked reduced incidences of liver tumors during 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) administration, which took more than 10 years. Previously, we observed that the Donryu rat liver was quite sensitive to both DNA-damaging and cytotoxic effects of 3'-Me-DAB, while the DRH rat liver showed tolerance to 3'-Me-DAB under the same conditions. In the present study, we examined mRNA levels related to the cytotoxic drug resistance mechanism in the livers of DRH and Donryu rats using RT-PCR. Contrary to our expectation, we observed rather similar levels of mRNAs between the two rat strains under the following conditions: i) mdr1 mRNA induction after 3'-Me-DAB administration. ii) MLP-2 mRNA reduction by 3'-Me-DAB administration, iii) MLP-2 mRNA induction after cholestasis and iv) constitutive levels of cMOAT gene expression. On the other hand, the levels of p53 mRNA and p53 protein in the Donryu rat liver were higher than those in DRH rat liver during 3'-Me-DAB administration, suggesting that the former were more sensitive to 3'-Me-DAB than DRH rat under these conditions. In conclusion, we failed to demonstrate the difference in the cytotoxic drug resistance mechanism between DRH and Donryu rats at least under the conditions examined in this study.     

Optical coherence tomography of successfully repaired idiopathic macular holes

PURPOSE: To present the cross-sectional retinal imaging results of optical coherence tomography in eyes with successfully repaired idiopathic macular hole and their relevance to visual recovery. METHODS: We studied 33 eyes with successful repair of an idiopathic macular hole through vitrectomy and fluid-gas exchange from 32 patients (11 men and 21 women) with ages ranging from 48 to 78 years, with a median age of 66 years. Preoperative conditions in eyes with primary surgery disclosed nine eyes with stage 2, 14 eyes with stage 3, and four eyes with stage 4 macular hole. An additional six eyes underwent a second surgery because the previous surgery was unsuccessful. Measurement of best-corrected visual acuity, slit-lamp biomicroscopy with fundus contact lens, fundus photographs, and optical coherence tomographic examination were performed between 6 and 9 months after surgery in 29 eyes and between 15 and 36 months after surgery in four eyes. RESULTS: Optical coherence tomographic images of the repaired macular holes were categorized into three patterns. U-type (normal foveal contour; 13 eyes) showed mildly to moderately backscattering layers with a smooth circular surface covering retinal pigment epithelium and choriocapillaris layers. In eyes with V-type (steep foveal contour; 13 eyes), the retinal pigment epithelium and choriocapillaris layers were covered with moderately backscattering layers with a notch. W-type (foveal defect of neurosensory retina; seven eyes) showed abruptly or gradually terminating sensory retinal layers to expose the surface of the retinal pigment epithelium and choriocapillaris layers. Postoperative acuity was well correlated with these patterns of optical coherence tomographic images. CONCLUSION: Assessment of successfully repaired idiopathic macular holes with optical coherence tomographic images provides a useful correlation with postoperative visual recovery.     

Promotion of acute‐phase skin wound healing by Pseudomonas aeruginosa C4‐HSL

A Pseudomonas aeruginosa quorum‐sensing system, which produces N‐(3‐oxododecanoyl)‐l ‐homoserine lactone (3‐oxo‐C₁₂‐HSL) and N‐butanoyl‐l ‐homoserine lactone (C₄‐HSL), regulates the virulence factors. In our previous study, 3‐oxo‐C₁₂‐HSL, encoded by lasI gene, was shown to promote wound healing. However, the effect of C₄‐HSL, encoded by rhlI gene, remains to be elucidated. We addressed the effect of C₄‐HSL on wounds in P. aeruginosa infection. Wounds were created on the backs of Sprague–Dawley SD rats, and P. aeruginosa PAO1 (PAO1) or its rhlI deletion mutant (ΔrhlI) or lasI deletion mutant (ΔlasI) was inoculated onto the wound. Rats were injected intraperitoneally with anti‐C₄‐HSL antiserum or treated with C₄‐HSL at the wound surface. PAO1 inoculation led to significant acceleration of wound healing, which was associated with neutrophil infiltration and TNF‐α synthesis. These responses were reversed, except for TNF‐α production, when ΔrhlI was inoculated instead of PAO1 or when rats were co‐treated with PAO1 and anti‐C₄‐HSL antiserum . In contrast, the healing process and neutrophil infiltration, but not TNF‐α synthesis, were accelerated when C₄‐HSL was administered in the absence of PAO1. This acceleration was not affected by anti‐TNF‐α antibody. These results suggest that C₄‐HSL may be involved in the acceleration of acute wound healing in P. aeruginosa infection by modifying the neutrophilic inflammation.     

Iodine-131 imaging using 284 keV photons with a small animal CZT-SPECT system dedicated to low-medium-energy photon detection

Objective

Iodine-131 is widely used for radionuclide therapy because of its β-particle and for diagnostic imaging employing its principal gamma ray. Since that principal gamma ray has the relatively high energy of 364 keV, small animal single-photon emission computed tomography (SPECT) imaging systems may be required to possess the ability to image such higher energy photons. The aim of this study was to investigate the possibility of imaging I-131 using its 284 keV photons instead of its 364 keV photons in a small animal SPECT imaging system dedicated to the detection of low-medium-energy photons (below 300 keV).

Methods

The imaging system used was a commercially available preclinical SPECT instrument with CZT detectors that was equipped with multi-pinhole collimators and was accompanied by a CT imager. An energy window for I-131 imaging was set to a photopeak of 284 keV with a low abundance compared with 364 keV photons. Small line sources and two mice, one of each of two types, that were injected with NaI-131 were scanned.

Results

Although higher counts occurred at the peripheral region of the reconstructed images due to the collimator penetration by the 364 keV photons, the shape of the small line sources could be well visualized. The measured spatial resolution was relatively poor (~1.9 mm for full width at half maximum and ~3.9 mm for full width at tenth maximum). However, a good linear correlation between SPECT values and the level of I-131 radioactivity was observed. Furthermore, the uptake of NaI-131 to the thyroid gland for the two mice was clearly identified in the 3D-SPECT image fused with the X-ray CT image.

Conclusion

We conclude that the use of an energy window set on the photopeak of 284 keV and the multi-pinhole collimator may permit I-131 imaging for a preclinical CZT-SPECT system that does not have the ability to acquire images using the 364 keV photons.

     

Magnetic resonance imaging assessment of tumorous lesions in the floor of the mouth: case reports and review of the literature

Objectives Magnetic resonance (MR) imaging may provide some information as to the extent and tissue characteristics of a cancerous mass, but the imaging features of lesions in the floor of the mouth have not been sufficiently clarified. MR imaging features of tumescent lesions in this region were characterized, and the differential diagnoses are discussed. Methods MR images of 12 patients with tumescent lesions in the floor of the mouth (three patients with squamous cell carcinoma, two with adenoid cystic carcinoma, one with hemangioma, one with schwannoma, one with lipoma, and four with ranula) were reviewed. The literature on the imaging features of tumescent disease in the floor of the mouth was searched using the Medline database. Results Six types of tumescent lesions in the floor of the mouth are presented. The differential diagnosis through a review of the references is discussed. Malignant tumors were demonstrated as ill-defined masses. MR images were good at showing the internal structures, such as fluid, hemorrhage, fat, nerves, calculus (phlebolith), cholesterol, and keratin, as different signal intensities. Therefore, MR images gave clues for the differential diagnosis. Conclusion MR images presented the distinctive features or the extent of the lesions and were therefore considered useful for a more accurate diagnosis prior to treatment.     

The association of platelet-derived growth factor (PDGF) receptor tyrosine phosphorylation to mitogenic response of human osteoblastic cells in vitro

OBJECTIVES: The purpose of this study was to make clear the relationship of human osteoblastic ceil growth, induced by platelet-derived growth factor (PDGF), to PDGF receptor tyrosine phosphorylation.
MATERIALS AND METHODS: Osteoblastic cells derived from human maxilla were cultured with human PDGF. The cell growth was evaluated by cell number and DNA synthesiS. PDGF receptor tyrosine phosphorylation was detected by immunoblot analysis using anti-PDGF receptor α, β subunits and anti-phosphotyrosine antibodieS. Genistein, a tyrosine kinase inhibitor, was added to the culture to investigate the effect on osteoblastic cell growth and PDGF receptor tyrosine phosphorylation induced by PDGF.
RESULTS AND CONCLUSIONS: PDGF stimulated the proliferation of human osteoblastic cells and this effect was synergetic with serum stimulation. DNA synthesis of osteoblastic cells was elevated by PDGF in a dose dependent manner at the minimum concentration of I ng ml^-1.PDGF also induced PDGF receptor tyrosine phosphorylation within 1 min on osteoblastic cells, and tyrosine phosphorylation occurred on PDGF receptor subunits α and β.Genistein inhibited cell growth and receptor tyrosine phosphorylation, which was induced by PDGF on these cellS. In conclusion, human osteoblastic cell growth induced by PDGF is shown to relate to tyrosine kinase of PDGF receptors.     

The effect of hyperbaric oxygen treatment on postoperative morbidity of left lobe donor in living donor adult liver transplantation

BACKGROUND/AIMS: In living donor liver transplantation (LDLT), donor safety has top priority, and donor morbidity should be minimized to zero. However, several corporal problems still remain. The effect of hyperbaric oxygenation treatment (HBO) was evaluated for donor morbidity in LDLT. METHODOLOGY: A total of 14 consecutive donors were studied. The donors into were divided into 2 groups as follows: HBO group (n=7), which started HBO 3 days after operation, and a control group (n=7). Patient's factors, graft volume, liver regeneration rate, liver function tests and postoperative complications ware compared between the 2 groups. RESULTS: There was no significant difference between the groups in whole liver, graft and remnant liver volume. The incidence of wound numbness on POD 28 was 86% (6/7) in the control group and 29% (2/7) in the HBO group (p<0.05). Postoperative hospital stay was 14.4 and 14.6 days in the control and HBO group, respectively (p=NS). On POD 14, AST value in the HBO group was significantly lower than in the control group (p<0.05). PT% value in the HBO group was significantly higher than in the control group on POD 14 (p<0.05). Total bilirubin level in the HBO group was significantly lower than in the control group on POD 14 and 28 (p<0.05), and total bile acid value in the HBO group was significantly lower than the control group (p<0.05) on POD 14. Albumin level in the HBO group was significantly higher than the control group on POD 7, 10 and 28 (p<0.05). Four weeks after the operation, the regeneration rate was significantly higher in the HBO group than in the control group (p<0.05). CONCLUSIONS: Liver regeneration was promoted by HBO preserving a function in LDLT using left lobe graft. Hyperbaric oxygen therapy seems to be very useful to LDLT.     

Polypoidal choroidal vasculopathy with choroidal vascular hyperpermeability

PURPOSE: To describe the incidence and clinical characteristics of polypoidal choroidal vasculopathy (PCV) associated with choroidal vascular hyperpermeability. DESIGN: Retrospective observational case series. METHODS: We reviewed the medical records of 122 consecutive eyes with PCV and 106 consecutive eyes with exudative age-related macular degeneration (AMD). Fluorescein angiography and indocyanine green (ICG) angiography were performed using a confocal scanning laser system. In the midphase of ICG angiography, we evaluated choroidal vascular hyperpermeability, which is recognized as one of the characteristic findings in central serous chorioretinopathy (CSC). Choroidal vascular hyperpermeability appeared as multifocal patchy areas of hyperfluorescence with blurred margins within the choroid that increased in intensity with time after injection of the dye. RESULTS: Of 122 eyes with PCV, 12 (9.8%) eyes of 10 patients exhibited multifocal choroidal hyperfluorescence in the midphase of ICG angiography, whereas two (1.9%) of 106 eyes with exudative AMD showed a similar appearance (P = .013). Of the 12 eyes in 10 patients with PCV that demonstrated multifocal choroidal hyperfluorescence, we also noted that the early phase of ICG angiography showed choroidal filling delay in seven eyes (58%) and venous dilation in 12 eyes (100%). Four of these 12 eyes (33%) had a medical history of CSC, and nine (90%) of the 10 patients revealed multifocal choroidal hyperfluorescence bilaterally. CONCLUSIONS: Multifocal choroidal hyperfluorescence seen by ICG angiography occurs more frequently in eyes with PCV than in those with AMD. Choroidal vascular hyperpermeability, reportedly a characteristic finding in CSC, might be one of the risk factors of PCV.     

Intraoperative fluoroscopic detection of an occult jejunal arteriovenous malformation

A case of chronic gastrointestinal hemorrhage caused by a small jejunal arteriovenous malformation is presented. After microcatheter and microcoil placement, the patient underwent laparoscopically assisted jejunal resection. Intraoperative localization was accomplished by combined use of methylene blue injection and contrast medium injection. Methylene blue injection demarcated the segment of bowel involved and fluoroscopy by contrast medium injection revealed the arteriovenous malformation. This technique located the arteriovenous malformation during surgery and insured adequate but not excessive bowel resection.