Characterization of normal and infarcted rat myocardium using a combination of small-animal PET and clinical MRI.

The combination of small-animal PET and MRI data provides quantitative in vivo insights into cardiac pathophysiology, integrating information on biology and morphology. We sought to determine the feasibility of PET and MRI for the quantification of ischemic injury in the rat model. METHODS: Fourteen healthy male Wistar rats were studied with 18F-FDG PET and cine MRI. Myocardial viability was determined in a transmural myocardial infarction model in 12 additional rats, using 18F-FDG PET and delayed-enhancement MRI with gadolinium-diethylenetriaminepentaacetic acid. All PET was acquired with a dedicated small-animal PET system. MRI was performed on a 1.5-T clinical tomograph with a dedicated small-animal electrocardiographic triggering device and a small surface coil. RESULTS: In normal rats, 18F-FDG uptake was homogeneous throughout the left ventricle. The lowest mean uptake of the 18F-FDG was found in the apical regions (79% +/- 6.0% of maximum) and the highest uptake was in the anterior wall (93% +/- 4.3 % of maximum). Myocardial infarct size as determined by histology correlated well with defects of glucose metabolism obtained with 18F-FDG PET (r = 0.89) and also with delayed-enhancement MRI (r = 0.91). Left ventricular ejection fraction in normal rats measured by cine MRI was 57% +/- 5.4% and decreased to 38% +/- 12.9% (P < 0.001) in the myocardial infarction model. CONCLUSION: Integrating information from small-animal PET and clinical MRI instrumentation allows for the quantitative assessment of cardiac function and infarct size in the rat model. The MRI measurements of scar can be complemented by metabolic imaging, addressing the extent and severity of ischemic injury and providing endpoints for therapeutic interventions.     

Pressure overload-induced transient oxidative stress mediates perivascular inflammation and cardiac fibrosis through angiotensin II.

Oxidative stress is implicated in the pathogenesis of various cardiovascular diseases. We have shown that in Wistar rats with a suprarenal aortic constriction (AC), pressure overload-induced transient perivascular inflammation (monocyte chemoattractant protein-1 [MCP-1] induction and macrophage accumulation) in the early phase is the determinant of reactive myocardial fibrosis and resultant diastolic dysfunction in the late phase. Thus, we investigated the role of reactive oxygen species production in cardiac remodeling in AC rats. Superoxide production and the footprint of lipid peroxidation were assessed using dihydroethidium staining and immunohistostaining against 4-hydroxy-2-nonenal (4-HNE), respectively. In sham rats, dihydroethidium and 4-HNE signals were scarcely found in the heart. At day 3, AC rats showed dihydroethidium signals mainly in the intramyocardial arterial wall, whereas modest 4-HNE staining was observed diffusely in the myocardium. These signals declined to lower levels by day 14 despite sustained hypertension. Chronic administration of a subdepressor dose of an angiotensin II type 1 receptor blocker candesartan reduced the pressure overload-induced dihydroethidium and 4-HNE signals at day 3. Moreover, candesartan decreased MCP-1 induction and macrophage infiltration at day 3 and prevented myocardial fibrosis at day 14, without affecting left ventricle and myocyte hypertrophy. In conclusion, acute pressure overload induced self-limited superoxide production mainly in the vascular wall. The reactive oxygen species production would contribute to the perivascular inflammation and subsequent myocardial fibrosis. Angiotensin II was suggested to have a pressure-independent effect on the reactive oxygen species production.     

Development of a simple image viewer designed for small X-ray field CT equipment 3DX

Objectives To develop a simple image viewer that utilizes image files in general-purpose formats that are written from the original 3DX volume data. Methods We used FLASH MX2004 for Macintosh to develop a simple image viewer. In developing the software for the simple image viewer, we decided that the viewer should provide the following features: (1) be available to both Windows OS and Mac OS, (2) allow interlocking of the 3D images, (3) display image enlargement, and (4) allow distance measurements. The accuracy of the distance measurements was evaluated. Results The procedure was as follows: (1) write 3D images in jpeg format to a folder on i-VIEW; (2) place the folder containing the 3D images into the directory of the simple image viewer software on a PC; (3) start the software and open the window to input the folder name containing the 3D images; and (4) display the 3D images. Our viewer had features such as image enlargement, interlocking 3D images, drawing, and distance measurements. No significant differences were shown between the measurements made by our simple viewer and the actual values of the images in any direction. Conclusions Our image-viewing software for 3DX is beneficial for clinical use.     

PEUTZ‐JEGHERS SYNDROME ASSOCIATED WITH RENAL AND GASTRIC CANCER THAT DEMONSTRATED AN STK11 MISSENSE MUTATION

A 75‐year‐old male was admitted to the gastroenterology unit of Nagoya City University Hospital due to epigastralgia after surgical treatment for right renal cancer. Endoscopy revealed advanced type 1 gastric cancer in the corpus of the stomach and multiple polypoid lesions in the stomach and duodenum. X‐ray examination of the small intestine using barium showed multiple polyps in the upper jejunum. Faint pigmentation on the palm was also detected. Peutz‐Jeghers syndrome (PJS) was diagnosed, despite a lack of family history. Total gastrectomy, resection of part of the upper jejunum and intraoperative endoscopic polypectomy of duodenal polyps was performed. This is the second reported case of PJS associated with renal cancer. We also detected a missense mutation in the tumor suppressor gene STK11 that, when mutated, is causative for PJS.     

Global gene profiling reveals a downregulation of BMP gene expression in experimental atrophic nonunions compared to standard healing fractures.

Nonunion is a challenging problem that may occur following certain bone fractures. However, there has been little investigation of the molecular basis of nonunions. Bone morphogenetic proteins (BMPs) play a significant role in osteogenesis. However, little is known about the expression patterns of BMPs in abnormal bone healing that results in nonunion formation. These facts prompted us to investigate and compare the gene expression patterns of BMPs and their antagonists in standard healing fractures and nonunions using rat experimental models. Standard closed healing fractures and experimental atrophic nonunions produced by periosteal cauterization at the fracture site were created in rat femurs. At postfracture days 3, 7, 10, 14, 21, and 28, total RNA was extracted from the callus of standard healing fracture and fibrous tissue of nonunion (n=4 per each time point and each group). Gene expression of BMPs, BMP antagonists, and other regulatory molecules were studied by methods including Genechip microarray and real-time quantitative RT-PCR. Gene expression of BMP-2, 3, 3B, 4, 6, 7, GDF-5, 7, and BMP antagonists noggin, drm, screlostin, and BAMBI were significantly lower in nonunions compared to standard healing fractures at several time points. Downregulation in expression of osteogenic BMPs may account for the nonunions of fracture. The balance between BMPs and their endogenous antagonists is critical for optimal fracture healing.     

Genetic susceptibility to herpetic encephalitis of inbred rabbits of B/Jas strain

Inbred rabbits of B/Jas strain were found to be highly susceptible to herpes simplex virus type 1 encephalitis, following i.v. injection of the virus, while Chbb:HM strain rabbits were not susceptible. The susceptibility trait seemed to be inherited recessively, involving multiple genes, because (B/Jas x Chbb:HM)Fl hybrids were as resistant as Chbb:HM rabbits, and because more than 90% of backcrosses of (B/Jas x Chbb: HM)FI to B/Jas were resistant to viral inoculation. The encephalitis in B/Jas rabbits resembled human herpes simplex encephalitis, in that the temporal lobe as well as the brain stem were affected preferentially, leading to the development of various types of seizures, such as circling, loss of balance leading to a fall, and tonic and clonic convulsions. The disease could be diagnosed by magnetic resonance imaging (MRI) analysis before onset of seizures, and diseased rabbits showed a marked lymphopenia at onset of seizures. © 1995 Wiley-Liss, Inc.     

Temporal and spatial expression of transforming growth factor-β in the healing patellar ligament of the rat

We investigated the temporal and spatial expression of transforming growth factor-β in the healing patellar ligament of the rat by immunohistochemistry. The mid-portion of the medial half of the patellar ligament in 14-week-old male Wistar rats was cut transversely with a scalpel. On day 1 after ligament injury, diffuse staining for transforming growth factor-β was observed in the extracellular matrix filling the wound, and the staining in the adjacent ligament tissue was as weak as it was in the normal ligament. On day 3, the intensity of the diffuse extracellular staining decreased, and the staining was observed in correspondence with the cellular distribution in the wound site and in the adjacent uninjured ligament tissue. On day 7, the intense staining was widely distributed over the whole length of the ligament tissue. On day 28, the staining for transforming growth factor-β was still observed at the wound site and in the adjacent uninjured ligament tissue, where the staining was reduced in intensity but still stronger than it was in the normal ligament. On day 56, the expression of transforming growth factor-β was still detectable at the wound site: however, in the adjacent uninjured ligament tissue, it had almost subsided to the normal level. The results of the present study suggest that ligament healing may be accompanied by extensive changes in the expression of transforming growth factor-β over the whole length of ligament tissue.