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Biomedical subjects

M Pech

Publications and source records attributed to M Pech.

At least 19 recordsLinked to original sources

Magnetic resonance imaging in the assessment of cystic pancreatic lesions: differentiation of benign and malignant lesion status.

PURPOSE: To characterize cystic pancreatic lesions and tumors with magnetic resonance imaging (MRI), and to assess the value of morphological criteria in differentiating pseudocysts versus cystic tumors and benign versus malignant cystic tumors. MATERIAL AND METHODS: Twenty-three patients with cystic pancreatic tumors or lesions underwent plain and contrast-material-enhanced MRI, including magnetic resonance cholangiopancreatography (MRCP). The MR findings were characterized and analyzed by two readers, and the role of various imaging criteria and combinations thereof for final lesion assignment were assessed. Final diagnoses were obtained from the results of open surgery (n = 19) and/or biopsy (n = 4). RESULTS: Final diagnoses included cystic tumors (n = 11) and pseudocysts (n = 12). The lesions were located in the head (56%) and body or tail (44%). Lesion diameters ranged from 7 to 50 mm. Various lesion contrast enhancement patterns were observed for both benign and malignant lesions. Serous cystadenomas were located in the head, they were lobulated, and had wall diameters < or = 2 mm; with the combination of these characteristics all patients with serous cystadenoma could be identified, whereas in no other patient was this constellation observed. CONCLUSION: MRI facilitated the diagnosis of serous cystadenomas, although no definite morphologic criterion for the differentiation between pseudocysts and mucinous cystadenomas was identified. In consideration of the substantial therapeutic consequences, either diagnostics in unclear cystic pancreatic lesions should comprise cyst fluid analysis if necessary, or eligible patients should be referred for surgical resection.

Adult↗

Hepatocellular carcinoma in association with hepatic focal nodular hyperplasia.

PURPOSE: To report the association between hepatocellular carcinoma (HCC) and hepatic focal nodular hyperplasia (FNH) and the possible impact on clinical decision-making with regard to resective approaches in patients with FNH. MATERIAL AND METHODS: We retrospectively analyzed the findings in 77 adult patients who underwent liver resections for FNH between October 1989 and September 2001 at our center. HCC within the confines of FNH was found in two patients. We demonstrate the magnetic resonance imaging (MRI) and macroscopic and microscopic findings. RESULTS: Presurgical MRI demonstrated heterogeneous signal characteristics of moderately hyperintense FNH on T2-weighted images and, after i.v. administration of superparamagnetic iron oxide particles, HCC in FNH was barely delineable. Both patients underwent successful right hemihepatectomy to remove the suspicious FNH with diameters of 12 and 14 cm; intralesional HCC diameters were 3 and 5 cm, respectively. Patients could be rapidly dismissed. However, one patient died after recurrence of HCC 1.5 years after surgery, whereas the other patient continues tumor-free 4 years after surgery. Alpha-feto-protein was normal in both patients. CONCLUSION: In FNH with rapid growth tendency and heterogenic MR appearance, surgical removal should be considered to overcome the risk of inadequate therapy in the very rare group of patients with HCC in association with FNH.

Carcinoma, Hepatocellular↗

[Evaluation of image quality of the Iso C3D image processor in comparison to computer tomography. Use in the pelvic area].

Intraoperative 3-D visualization using the Siremobil Iso C(3D) (Siemens, Erlangen, Germany) has been approved for use in spine and long bone surgery since its recent clinical launch. In preparation for the clinical use of the Siremobil Iso C(3D) in pelvic surgery, the aim of this study was to grade the quality of visualization in comparison with the gold standard of computer tomography in four therapy relevant pelvic regions in eight human cadavers, including SI screws to exemplify implants in the dorsal pelvic ring. Besides the influence of the body mass index and the interference of metal artefacts, visualization quality was evaluated in different pelvic regions (sacroiliac joint, acetabulum, femoral neck and anterior pelvic ring) using a score with five subgroups, rating the applicability of Siremobil Iso C(3D) in pelvic surgery. The grading of image quality in comparable standard projections was performed independently by three surgeons and three radiologists.Visualization quality appeared sufficient for both intraoperative and postoperative control in cases with a known preoperative diagnosis. There was no influence of body mass index found in any of the eight cadavers. Implants positioned in the dorsal pelvic ring reduced visualization quality, but sufficient estimation of bony structures was still possible. For primary diagnostics, computer tomography remains a clearly superior option due to better image quality. For intraoperative control of the reduction and positioning of implants in pelvic surgery, however, the additional intraoperative use of Siremobil Iso C(3D) is considered to offer clear advantages over current 2-D C-arm visualization tools.

Cadaver↗

[Comparison of radiation dose and image quality of Siremobil-IsoC(3D) with a 16-slice spiral CT for diagnosis and intervention in the human pelvic bone].

PURPOSE: To compare the image quality of 16-slice computed tomography with the image quality of Siremobil-IsoC (3D) of the pelvic region and to measure simultaneously the radiation dose before and after implantation of a sacroiliac screw (SI-screw) MATERIALS AND METHODS: The pelvic region of 8 human cadavers was examined in the Siremobil-IsoC (3D) at five different levels. We used a standard protocol for the 16-slice CT of the complete pelvic region before and after insertion of a pelvic screw, followed by stepwise reduction of the tube current to find the tube current that equalizes the image quality of both modalities. We controlled the image quality by judging important structures such as neuroforamen, nerves, sacroiliacal joint space, intervertebral space, osteophytes, iliopsoas muscle, acetabular surface, fovea centralis, hip joint and os pubis. The image quality was judged by three radiologists and three trauma surgeons using a ranking from 1 to 5. The dose was measured with an endorectally placed NOMEX Dosimeter, to obtain the gonadal dose. RESULTS: The medium score for all viewers of the Siremobil-IsoC (3D) examinations was between 3 and 4.3. The medium score for all CT-examinations with a tube current of 250 mA was between 1.3 and 2.2. The reduction of tube current down to 80 mA hardly influenced the marks for the analyzed structures. Under 80 mA, bony structures, even after implantation of a SI-screw, were still marked as good, but soft tissue differentiation was getting worse. For the examination of the pelvis, the average dose-length product for the IsoC (3D) was 41.2 mGy x cm. The medium dose-length product for CT was 389 mGy x cm for 250 mA, 125 mGy x cm for 80 mA and 82 mGy x cm for 60 mA. CONCLUSION: The Siremobil-IsoC (3D) is sufficient for therapeutic intraoperative purpose, but the image quality is not sufficient for diagnostic purpose. The higher dose-length product of a CT examination is justifiable because of a better overview, shorter examination time and qualitative superiority. An advantage of the Siremobil-IsoC (3D) is the intraoperative availability with acceptable 3D image quality compared to conventional fluoroscopy.

Bone Screws↗

Magnetic resonance cholangiopancreatography: image quality, ductal morphology, and value of additional T2- and T1-weighted sequences for the assessment of suspected pancreatic cancer.

PURPOSE: To assess image quality and duct morphology on magnetic resonance cholangiopancreatography (MRCP) and also the value of additional T2- and T1-weighted sequences for differentiation of benignity and malignancy in patients with suspected pancreatic tumors. MATERIAL AND METHODS: One-hundred-and-fourteen patients received MRCP and unenhanced and contrast material-enhanced MR imaging. MR results were analyzed independently by two blinded readers, and subsequently correlated with the results from surgery, biopsy, and follow-up. Assessment included the evaluation of image quality, duct visualization and morphology, and the differentiation of pancreatic lesion status (benign versus malignant). RESULTS: Overall, 49 patients had benign final diagnoses, while 65 had a malignant diagnosis. Image quality of single-shot thick-slab MRCP was rated significantly better than the MIP images of multisection MRCP. With MRCP alone, the two readers' accuracy in the assessment of pancreatic lesion status was 72% (95% CI, 64% to 83%) and 69% (95% CI, 56% to 77%), respectively; with the addition of T2- and T1-weighted images the accuracy significantly improved to 89% (95% CI, 82% to 95%) and 84% (95% CI, 77% to 92%) for readers 1 and 2, respectively. CONCLUSION: Single-shot thick-slab MRCP and multisection MRCP provide complementary results; however, single-shot MRCP had superior image quality. Moreover, assessment of ductal morphology with MRCP alone facilitated the diagnosis of different pathologic conditions of the pancreatobiliary system in the majority of patients. However, with the addition of T2- and T1-weighted sequences the overall diagnostic accuracy was significantly improved and thus we consider that a comprehensive MR approach should comprise both MRCP techniques and parenchymal sequences.

Adult↗

Magnetic resonance imaging including magnetic resonance cholangiopancreatography for tumor localization and therapy planning in malignant hilar obstructions.

PURPOSE: To assess image quality and overall accuracy of magnetic resonance imaging (MRI), including two magnetic cholangiopancreatography (MRCP) techniques, for the diagnostics and preoperative work-up of malignant hilar obstructions. MATERIAL AND METHODS: Thirty-one patients with malignant hilar obstructions (hilar cholangiocarcinoma, n=30; hepatocellular carcinoma, n=1) received MRCP by two techniques (single-shot thick-slab and multisection thin-slice MRCP) and unenhanced and contrast material-enhanced MRI. MR assessment included the evaluation of image quality and visualization of bile ducts (5-point scale), and the classification of tumor status. MR results were subsequently correlated with the results from surgery and pathology. RESULTS: The maximum intensity projections of multisection thin-slice MRCP had significantly more artifacts compared to MRCP in the single-shot thick-slab technique, and overall image quality of single-shot thick-slab MRCP was rated significantly superior compared to multisection thin-slice MRCP (4.4 +/- 0.7 and 4.1 +/- 0.9, respectively). Moreover, ductal visualization of different parts of the biliary system was rated superior with single-shot thick-slab MRCP. In contrast, the original data from multisection thin slice MRCP facilitated visualization of periductal lesions and adjacent structures. Overall MR accuracy for the assessment of tumor status, periductal infiltration, and lymph node metastases was 90%, 87%, and 66%, respectively. CONCLUSION: For evaluation of malignant hilar obstructions, MRCP by the single-shot thick-slab technique had superior image quality and fewer artifacts; in contrast, besides sole biliary visualization, multisection MRCP depicted complementary adjacent parenchymal and periductal structures. We therefore recommend MRI, with a combination of both MRCP techniques, for the diagnostic work-up and therapy planning of malignant hilar obstructions.

Adult↗

[CT-guided interstitial brachytherapy of lung malignancies. Technique and first results].

CT-guided interstitial brachytherapy of lung malignancies is a novel technique combining (192)Iridium brachytherapy with modern CT guidance for applicator positioning and 3D dosimetry. Initially, this technique has been developed for the treatment of liver malignancies. In the following we describe this novel technique as well as initial results for the treatment of lung malignancies.

Brachytherapy↗

[Comparison of different MRI sequences with and without application of Gd-BOPTA as follow-up after LITT].

PURPOSE: Comparison of various MR imaging techniques without and with the application of Gd-BOPTA for the follow-up of thermal tumor ablations by means of laser-induced therapy (LITT). MATERIALS AND METHODS: Thermal tumor ablations were performed with LITT in 19 patients showing a local recurrence. The metastases were from colorectal carcinoma in 15 cases (78.9 %) and from cervix, bronchial, gastric and renal carcinoma respectively in one patient each. The size of the metastases before ablation was on average 38.5 mm (min = 25 mm, max = 58 mm). The MRI protocol consisted of T2 UTSE FS, T1 w GRE without and with Gd-BOPTA at an early (20 s post injection) and late stage (> 120 min post injection). Two independent radiologists evaluated image contrast of the local relapse and necrosis in comparison to the surrounding healthy liver parenchyma on a scale from - 10 to + 10. Liver parenchyma was in any sequence 0. Recurrences were confirmed with follow-up examinations in all patients. Statistical analysis was performed by means of Wilcoxon and Kendall's W-test. RESULTS: Both radiologists found absolute ratios for contrast differences between thermal necrosis and local recurrence, with an average of 10.95 for T2 w UTSE FS and of 6.58 for T1 w GRE without, and of 4.05 for T1 w GRE with Gd-BOPTA in the early and of 2.26 in the late stage. Superiority for UTSE FS was significant (p < 0.05). The statistical analysis showed a high agreement for both radiologists for all values (p < 0.001). CONCLUSION: For early detection of local recurrences after thermal ablation T2 w UTSE FS is most suitable. For the detection of new foci, the use of liver specific contrast media is advisable.

Contrast Media↗

[The diagnostic value of radial multiplanar reformatting (MPR) in the CT-diagnosis of pulmonary embolism].

PURPOSE: To evaluate the diagnostic value of radial reformatting of axial multislice CT (MS-CT) data sets in the presumptive diagnosis of pulmonary embolism. MATERIALS AND METHODS: In 126 cases with the presumptive diagnosis of an acute pulmonary embolism, 4- and 8-slice axial MS-CT data sets were radially reformatted. The pulmonary vessels were evaluated by five experienced radiologists who determined the number of thrombi at the level of the segmental and subsegmental arteries. A pulmonary artery was considered as thrombosed if it showed at least one unambiguous filling defect on two consecutive sections. It was determined whether the artery was uniformly opacified without filling defects, contained thrombotic material or was completely occluded by a blood clot. Pulmonary vessels that could not be evaluated because of moving artifacts or inadequate opacification were classified as negative. Finally, all experts gave a subjective estimate concerning the simplicity of the diagnosis for both reconstructions. RESULTS: The diagnosis of thromboembolism at a subsegmental level was significantly different for axial sections and radial reconstruction: at 4-slice CT, 77 subsegmental thromboembolisms were found in axial sections vs. 98.6 in radial reconstructions; at 8-slice CT, 23.6 in axial sections vs. 31.2 in radial reconstructions; and using the combined evaluation, 103.2 in axial sections vs. 130.6 in radial reconstructions, with a significance of p = 0.043. The five judges did not find any significant differences in the number of the blood clots in each pulmonary segment. Concerning the simplicity of the diagnosis, the subjective judgment classified the radial reconstructions as better in 49.7 % and the axial sections as better in 22 %. The radial reconstructions of the 4-slice CT were classified as better in 45.7 % vs. 25 % and the 8-slice CT as better in 66 % vs. 16 %. CONCLUSION: Using radial multiplanar reformatting of the MS-CT data sets improves significantly the recognition of subsegmental pulmonary embolism.

Acute Disease↗

Computed tomography-guided pulmonary nodule localization before thoracoscopic resection.

PURPOSE: To assess the success rate and complication rate of a CT-guided pulmonary nodule-marker system before thoracoscopic resection. MATERIAL AND METHODS: In 24 patients (15 M, 9 F; age range, 18-71 years) a total of 25 pulmonary nodules (in 1 patient 2 lesions simultaneously) were marked with a special wire under CT-guidance and then thoracoscopically resected. We evaluated lesion size, lesion distance to the pleura, the time of intervention, complications, and thoracoscopic success rate. RESULTS: Mean lesion size was 7 mm (range 4-15 mm) and mean lesional distance to the pleura was 13 mm (range 2-31 mm). The pulmonary nodule-marker system was positioned successfully in all 25 pulmonary nodules within 5-11 min (mean 7.5 min). Minimal pneumothoraces were observed in five patients with no requirements of chest drains. In addition, no bleeding complications or hematothorax were observed. All 25 pulmonary nodules could be resected thoracoscopically. However, in one patient (4%), the guide-wire dislocated during thoracoscopy, but the lesion could be successfully resected during thoracoscopy. CONCLUSION: The CT-guided placement of the pulmonary nodule-marker system used here offers a safe and accurate guide for the localization of small pulmonary nodules during thoracoscopic resection.

Adolescent↗

[Application of multislice detector spiral computed tomography to intracranial aneurysms: first clinical experience].

PURPOSE: To identify advantages when using the new multislice spiral CT technology (MSCT) for the detection and demonstration of intracranial aneurysms with CT angiography (CTA)? MATERIAL AND METHODS: Patients with suspected intracranial aneurysms underwent 4- and 8-slice spiral CTA. Image postprocessing included "maximum intensity projection" (MIP),"volume rendering" (VR) and additionally curved multiplanar reconstructions (MPR) for aneurysms suspected at the carotid siphon. The results were compared with those achieved with digital subtraction angiography (DSA). RESULTS: In 19 patients 21 out of 22 aneurysms were detected by CTA. A high resolution three-dimensional view of the aneurysm morphology in spatial relation to the surrounding structures was achieved. Further information could be gained by making a detailed examination of the inside wall of the aneurysm, using virtual vascular 3D-endoscopy and virtual 3D-craniotomy. CONCLUSION: Compared to DSA,MS-CTA is a useful additional and in selected cases alternative modality for the detection with marked advantages in the demonstration of intracranial aneurysms.

Adult↗

Comparison of indirect CsI/a:Si and direct a:Se digital radiography. An assessment of contrast and detail visualization.

PURPOSE: To assess and quantify the image quality at two dose levels for an amorphous Silicon (a:Si) Cesium Iodide (CsI) flat panel system compared with a direct amorphous Selenium (a:Se) digital radiography system. MATERIAL AND METHODS: A contrast detectability test was performed employing the CDRAD-phantom at mAs-values leading to approximately equal phantom entrance doses of 41.4, 57.9, 75.1 and 120.8 micro Gy for the a:Se and 39.9, 58.4, 75.6 and 117.9 micro Gy for the CsI system. Images were presented to 4 independent observers. For quantitative comparison, the image quality figure (IQF) was calculated. Statistical analysis was performed using Pearson's correlation and the Wilcoxon test. A ROC-analysis was performed employing the TRG-phantom in a high- and a low-dose setting leading to entrance doses of 126.2 and 35 micro Gy for the direct, and 125.9 and 34.4 micro Gy for the indirect system. Statistical significance was evaluated using the Wilcoxon test. RESULTS: The flat panel a:Si digital system provided superior results compared with the a:Se drum digital system with respect to low-dose settings for CDRAD-phantom and ROC-analysis, ensuring a better image quality with respect to contrast and detail detectability. Higher-dose settings provided similar results for both systems. CONCLUSION: Image quality of a:Si flat panel digital radiography proved to be superior to a:Se drum digital radiography using low-dose settings. If the primary target is dose reduction indirect flat panel technology should be used.

Cesium↗

[System continuity and energy distribution in laser-induced thermo therapy (LITT)].

PURPOSE: Evaluation of the continuity and energy distribution of a laser system for laser-induced thermo therapy. MATERIAL AND METHODS: For evaluation of the continuity of laser optical devices, laser generating units and optical fibers of three different manufactures (Dornier, Hüttinger, Somatex), we used the equipment to generate a laser beam of 25 Watt for 60 minutes. Measurements of the applied energy were done sequentially with two MY Test (Fa. Hüttinger) units. We also performed two in vitro ablations of animal liver tissue with different fiber optics [Mikrodom A 13-0540, Microflexx REF A 13-0561 (Hüttinger), Diffusor-Tip H-6111-T 3, Diffusor H-6111-T 4 (Dornier), Somaflex-Diffusor (Somatex)] over 20 minutes at- an energy flow of 25 J per second. We then evaluated the geometry of coagulation. RESULTS: The different equipment used for our tests showed differences of a maximum of 10 %. Some components did not work properly in certain configurations even though the manufacturer assured it would. We saw significant differences in the ablation characteristics of the different fiber optics, especially in axial and frontal directions. CONCLUSION: Knowledge of the different characteristics in energy distribution and ablation characteristics are an important factor in performing a successful laser-induced thermo therapy.

Animals↗

Connective tissue growth factor (CTGF) stimulates vascular smooth muscle cell growth and migration in vitro.

Connective tissue growth factor (CTGF) was first identified as a 38-kDa cysteine-rich protein which can be specifically induced by TGF-beta and was recently found to be expressed abundantly in atherosclerotic lesions, but only marginally in normal vascular tissues. It was hypothesized that CTGF is one of the factors involved in the development of atherosclerotic lesions. In this study, we investigated the functions of CTGF protein in regulating the growth and migration of vascular smooth muscle cells (VSMC) and found that by overexpressing CTGF in VSMC, proliferation and migration rates were significantly increased. The accelerated growth and migration can be reversed by an anti-CTGF antibody. In addition, overexpression of CTGF also promotes VSMC to express more extracellular matrix protein collagen I and fibronectin. Our results indicate that CTGF is a growth factor for VSMC and it may play a similar role in promoting VSMC proliferation, migration, and formation of extracellular matrix, in vivo.

Animals↗

Expression of connective tissue growth factor (CTGF) mRNA in plaques of human anterior subcapsular cataracts and membranes of posterior capsule opacification.

PURPOSE: To investigate the correlation between connective tissue growth factor (CTGF) mRNA expression and immunohistochemical characteristics of anterior subcapsular cataract (ASC) formation as well as posterior capsule opacification (PCO) development (expression of type I collagen, alpha-smooth muscle actin and tenascin) under in vivo and under in vitro conditions in human and porcine lens epithelial cells. METHODS: CTGF mRNA expression was investigated using in situ hybridization and RT-PCR. Expression of type I collagen, alpha-smooth muscle actin and tenascin was detected by immunohistochemical staining. RESULTS: CTGF mRNA was expressed in human cataractous plaques of ASC and human PCO membranes, and appeared simultanously with the expression of type I collagen, alpha-smooth muscle actin and tenascin. CONCLUSION: The predominant expression of CTGF mRNA in human ASC and human PCO membranes suggests a significant role of CTGF in the pathological course of these ocular disorders.

Actins↗

Platelet-derived growth factor-induced vasodilatation in mesenteric resistance arteries by nitric oxide: blunted response in spontaneous hypertension.

Platelet-derived growth factor (PDGF) is a potent mitogen for vascular smooth-muscle cells, but its effects on vasomotion remain controversial. Both vasoconstriction and vasodilatation of isolated rat aortic rings have been reported. The effects of PDGF on responses of perfused mesenteric resistance arteries from normotensive Wistar-Kyoto and spontaneously hypertensive rats were studied by using a video dimension analyzer. PDGF receptor messenger RNA (mRNA) expression in endothelial cells isolated from mesenteric arteries of both normotensive and hypertensive rats was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. In both normotensive and hypertensive rats, PDGF-BB concentration-dependently induced vasodilatation (maximal response, 25 +/- 4% and 13 +/- 4% at 10(-8) M, respectively; p < 0.05, normotensive vs. hypertensive rats). Endothelium removal or preincubation with N(omega)-nitro-L-arginine methyl ester, but not indomethacin, inhibited these relaxations, indicating that these vasodilatations are endothelium dependent and mediated by nitric oxide. RT-PCR analysis showed that both PDGF-alpha and -beta receptor mRNAs were present in endothelial cells of the mesenteric arteries of normotensive as well as hypertensive rats. In addition, relaxations induced by both PDGF-AA and -AB were significantly less than those induced by PDGF-BB in both strains, suggesting that vasodilatation is mediated mainly by the PDGF-beta receptor subtype. No vasoconstriction was observed after application of PDGF-BB to both normotensive and hypertensive mesenteric arteries with or without endothelium. In rat mesenteric resistance arteries, PDGF induces endothelium-dependent vasodilatation mediated by nitric oxide. At sites where PDGF is released or locally produced, therefore, the growth factor may participate in regulating vascular tone, and this endothelium-dependent regulation is attenuated in spontaneous hypertension.

Animals↗

A quantitative method for determination of endothelial mRNA expression in vivo: induction of platelet-derived growth factor by endotoxin.

Quantitation of mRNA expression by endothelial cells in vivo has been limited to larger animals from which sufficient amounts of RNA could be isolated for Northern blot analysis. In the present study, we established a technique to isolate endothelial RNA from rat aortas using en face preparations. This RNA was not contaminated with RNA from smooth muscle cells as demonstrated by the absence of smooth muscle alpha-actin RNA. Following lipopolysaccharide (LPS) administration to rats, quantitation of platelet-derived growth factor (PDGF) ligand and receptor mRNA expression was carried out by competitive reverse transcriptase-polymerase chain reaction and normalized to glyceraldehyde-3 phosphate dehydrogenase. The results of the competitive reverse transcriptase-polymerase chain reaction were compared with those obtained by en face in situ hybridization. Aortic endothelium showed a 140-fold increase in PDGF-A mRNA expression 4 hours after LPS injection. Expression levels of this growth factor declined to near base line levels within 36 hours of the LPS injection. A 52-fold increase in PDGF-B mRNA was seen at 12 hours after LPS injection but expression levels were approximately 300-fold lower than for PDGF-A. These data indicate that changes in PDGF expression by endothelium in vivo can greatly exceed those observed in cultured cells. This method should permit study of endothelial gene regulation in a variety of pathological conditions in vivo.

Actins↗

Human connective tissue growth factor is expressed in advanced atherosclerotic lesions.

BACKGROUND: Atherosclerosis affects certain but not all vascular beds of the human circulation. Its molecular mechanisms are only partially understood. Human connective tissue growth factor (hCTGF) is a novel cysteine-rich, secreted polypeptide. hCTGF is implicated in connective tissue formation, which may play an important role in atherosclerosis. METHODS AND RESULTS: By using a differential cloning technique, we isolated a cDNA clone from a human aorta cDNA library, which is identical to hCTGF. Northern analysis shows that hCTGF mRNA was expressed at 50- to 100-fold higher levels in atherosclerotic blood vessels compared with normal arteries. In vascular smooth muscle cells, high-level expression of hCTGF mRNA was induced by transforming growth factor-beta 1. Using in situ hybridization and immunohistochemistry, we found that all advanced atherosclerotic lesions of human carotid arteries (eight patients; mean age, 69; age range, 57 to 85 years) and femoral arteries (two patients; mean age, 71.5 years) that we tested expressed high levels of both hCTGF mRNA and protein. hCTGF expression was localized mainly to smooth muscle cells in the plaque lesions that are negative for proliferating cell nuclear antigen staining. In addition, some CD-31-positive endothelial cells of plaque vessels expressed high levels of hCTGF mRNA and protein. hCTGF-positive cells were found predominantly in areas with extracellular matrix accumulation and fibrosis. In contrast, in normal arteries, we were unable to detect either hCTGF mRNA or immunoreactive hCTGF protein. CONCLUSIONS: In the present study, we have shown for the first time that both hCTGF mRNA and protein are expressed in human arteries in vivo and that hCTGF may represent a novel factor expressed at high levels specifically in advanced lesions and may play a role in the development and progression of atherosclerosis.

Adult↗