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Biomedical subjects

A Zimmermann

Publications and source records attributed to A Zimmermann.

At least 73 records · Page 4Linked to original sources
PubMed2001

Enhanced glypican-3 expression differentiates the majority of hepatocellular carcinomas from benign hepatic disorders.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a common malignant tumour worldwide, and its differential diagnosis from benign lesions of the liver is often difficult yet of great clinical importance. In the present study, we analysed whether glypican-3 is useful in differentiating between benign and malignant liver diseases and whether it influences the growth behaviour of HCC. METHODS: Northern blot analysis and in situ hybridisation. RESULTS: Northern blot analysis indicated that expression of glypican-3 mRNA was either low or absent in normal liver, in focal nodular hyperplasia (FNH), and in liver cirrhosis. In contrast, expression of glypican-3 mRNA was markedly increased in 20 of 30 and moderately increased in five of 30 HCC samples. The average increase in glypican-3 mRNA expression in HCC was significant compared with expression in normal liver (21.7-fold increase, p<0.01). In comparison with FNH or liver cirrhosis, glypican-3 mRNA expression in HCC was increased 7.2- (p<0.05) and 10.8-fold (p<0.01), respectively. In addition, pushing HCCs exhibited significantly higher glypican-3 mRNA expression than invading tumours (p<0.05). In situ hybridisation analysis demonstrated weak expression of glypican-3 mRNA in normal hepatocytes and bile ductular cells, and weak to occasionally moderate signals in hepatocytes forming nodules of liver cirrhosis and in regenerated hepatic nodules of FNH. In contrast, glypican-3 in situ hybridisation signals were intense in hepatic cancer cells with even higher levels in pushing HCCs than in invading HCCs. CONCLUSIONS: These findings suggest that glypican-3, in many cases, has the potential to differentiate between benign and malignant liver diseases.

Adult↗
PubMed2001

Cyclooxygenase 2 expression in chronic pancreatitis: correlation with stage of the disease and diabetes mellitus.

BACKGROUND: Fibrotic replacement of the exocrine pancreatic parenchyma and infiltration of inflammatory cells are the main characteristics of chronic pancreatitis (CP). Inflammation involves prostaglandin production in numerous inflammatory and noninflammatory cells, and cyclooxygenase 2 (COX-2) is the dominant regulator of prostaglandin synthesis. AIMS: In the present study, we analyzed the expression of COX-2, the key enzyme for prostaglandin synthesis in pancreatic tissues, and evaluated its relation to exocrine and endocrine tissue alterations in CP. PATIENTS AND METHODS: Pancreatic tissue specimens from 27 patients undergoing pancreatic head resection for CP were included in the study. Pancreatic tissues from 14 organ donors served as controls. The tissue specimens were analyzed histopathologically and for COX-2 immunoreactivity. RESULTS: In normal pancreatic tissue samples, COX-2 immunoreactivity was restricted to islet cells. In contrast, in early-stage CP, islets as well as ductal cells showed intense COX-2 immunoreactivity. In advanced-stage CP, ductal cells were still strongly positive for COX-2, yet islets displayed a variable COX-2 staining pattern which was associated with the distribution of insulin-positive cells and with the clinical diabetes mellitus status of the patient. Thus, patients with normal or latent diabetes mellitus status showed COX-2 immunoreactivity, whereas in diabetic patients the COX-2 immunoreactivity was decreased or absent in pancreatic islets. CONCLUSION: The presence of COX-2 in ductal cells of early and advanced CP, the relationship between COX-2 and insulin expression in the islets, and the diabetes mellitus status of CP patients suggest that this enzyme plays a role in the pathogenesis of exocrine and endocrine damage in CP.

Adult↗
PubMed2001

Co-existent chronic pancreatitis and pancreatic neuroendocrine tumor. Case report and review of the literature.

BACKGROUND: Few reports exist in the literature regarding neuroendocrine tumors either presenting as, or associated with, chronic pancreatitis. We report a case of chronic pancreatitis with a coexisting neuroendocrine tumor (gastrinoma) of the body of the pancreas. The available literature is reviewed. METHODS: Patient data including history, surgical procedure, histology and radiology investigations were collected and summarized. A Medline search using the key words 'pancreatitis' and 'neuroendocrine tumors' was performed for the years 1966-1999. Cited references in the relevant papers not listed in Medline databases were also evaluated. RESULTS: A 64-year-old female patient was operated on for unclear cystic lesions in the head and tail of the pancreas. Intraoperatively, a gastrinoma was incidentally discovered in the body of the pancreas. It did not appear to be obstructing the main pancreatic duct. The patient underwent a distal pancreatectomy with pancreatico-jejunostomy. Four months postoperatively, she is doing well with no signs of tumor recurrence. The Medline search revealed 125 publications, of which only 17 dealt with either acute or chronic pancreatitis associated with neuroendocrine tumors. When all available data were included, there were 26 cases of neuroendocrine tumors associated with acute pancreatitis. Additionally, 11 cases were associated with chronic pancreatitis, of which only 3 appear to be merely coexistent with chronic pancreatitis without an apparent cause-and-effect relationship between these two entities. CONCLUSION: We report the rare co-existence of chronic pancreatitis and a neuroendocrine tumor (gastrinoma) of the pancreas. The cause-and-effect relationship between neuroendocrine tumors of the pancreas and chronic pancreatitis continues to be uncertain. However, when the etiology of chronic pancreatitis is unclear, rare neuroendocrine tumors of the pancreas might be considered. Questions remain with regard to the potential role of chronic pancreatitis in the pathogenesis of pancreatic neuroendocrine tumors.

Carcinoma, Neuroendocrine↗
PubMed2001

Comparative analysis of galectins in primary tumors and tumor metastasis in human pancreatic cancer.

Galectins are galactoside-binding proteins that exhibit an important function in tumor progression by promoting cancer cell invasion and metastasis formation. Using Northern blotting and Western blotting analysis, in situ hybridization (ISH), and immunohistochemistry (IHC), we studied galectin-1 and galectin-3 in tissue samples of 33 primary pancreatic cancers and in tumor metastases in comparison to 28 normal pancreases. Furthermore, the molecular findings were correlated with the clinical and histopathological parameters of the patients. Northern blotting and Western blotting analysis showed significantly higher galectin-1 and galectin-3 mRNA and protein levels in pancreatic cancer samples than in normal controls. For galectin-1, no ISH signals and immunoreactivity were observed in acinar or ductal cells in the normal pancreas and in pancreatic cancer cells, whereas fibroblasts and extracellular matrix cells around the cancer mass exhibited strong mRNA signals and immunoreactivity. Galectin-3 mRNA signals and immunoreactivity were strongly present in most pancreatic cancer cells, whereas in the normal controls only faint ISH and IHC signals were seen in some ductal cells. Metastatic pancreatic cancer cells exhibited moderate to strong galectin-3 immunoreactivity but were negative for galectin-1. No relationship between the galectin-1 and galectin-3 mRNA levels and the tumor stage or between the IHC staining score and the tumor stage was found. However, galectin-1 mRNA levels and the IHC staining score were significantly higher in poorly differentiated tumors compared with well/moderately differentiated tumors, whereas for galectin 3 no differences were found. The expression pattern of galectin-1 and galectin-3 in pancreatic cancer tissues indicates that galectin-1 plays a role in the desmoplastic reaction that occurrs around pancreatic cancer cells, whereas galectin-3 appears to be involved in cancer cell proliferation. High levels of galectin-3 in metastatic cancer cells suggest an impact on metastasis formation.

Adenocarcinoma↗
PubMed2001

mTHPC-mediated photodynamic diagnosis of malignant brain tumors.

Radical tumor resection is the basis for the prolonged survival of patients suffering from malignant brain tumors such as glioblastoma multiforme. We have carried out a phase-II study involving 22 patients with malignant brain tumors to assess the feasibility and the effectiveness of the combination of intraoperative photodynamic diagnosis and fluorescence-guided resection (FGR) mediated by the second-generation photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC). In addition, intraoperative photodynamic therapy (PDT) was performed. Several commercially available fluorescence diagnostic systems were investigated for their applicability in clinical practice. We have adapted and optimized a diagnostic system that includes a surgical microscope, an excitation light source (filtered to 370-440 nm), a video camera detection system and a spectrometer for clear identification of the mTHPC fluorescence emission at 652 nm. Especially in regions of faint fluorescence, it turned out to be essential to maximize the spectral information by optimizing and matching the spectral properties of all components, such as excitation source, camera and color filters. To sum up, on the basis of 138 tissue samples derived from 22 tumor specimens, we have been able to achieve a sensitivity of 87.9% and a specificity of 95.7%. This study demonstrates that mTHPC-mediated intraoperative FGR followed by PDT is a highly promising concept in improving the radicality of tumor resection combined with a therapeutic approach.

Adult↗
PubMed2001

Development and characterization of an animal model of carnitine deficiency.

Mammals cover their carnitine needs by diet and biosynthesis. The last step of carnitine biosynthesis is the conversion of butyrobetaine to carnitine by butyrobetaine hydroxylase. We investigated the effect of N-trimethyl-hydrazine-3-propionate (THP), a butyrobetaine analogue, on butyrobetaine hydroxylase kinetics, and carnitine biosynthesis and body homeostasis in rats fed a casein-based or a vegetarian diet. The K(m )of butyrobetaine hydroxylase purified from rat liver was 41 +/- 9 micromol x L(-1) for butyrobetaine and 37 +/- 5 micromol x L(-1) for THP, and THP was a competitive inhibitor of butyrobetaine hydroxylase (K(i) 16 +/- 2 micromol x L(-1)). In rats fed a vegetarian diet, renal excretion of total carnitine was increased by THP (20 mg.100 g(-1) x day(-1) for three weeks), averaging 96 +/- 36 and 5.3 +/- 1.2 micromol x day(-1) in THP-treated and control rats, respectively. After three weeks of treatment, the total carnitine plasma concentration (8.8 +/- 2.1 versus 52.8 +/- 11.4 micromol x L(-1)) and tissue levels were decreased in THP-treated rats (liver 0.19 +/- 0.03 versus 0.59 +/- 0.08 and muscle 0.24 +/- 0.04 versus 1.07 +/- 0.13 micromol x g(-1)). Carnitine biosynthesis was blocked in THP-treated rats (-0.22 +/- 0.13 versus 0.57 +/- 0.21 micromol x 100 g(-1) x day(-1)). Similar results were obtained in rats treated with the casein-based diet. THP inhibited carnitine transport by rat renal brush-border membrane vesicles competitively (K(i) 41 +/- 3 micromol x L(-1)). Palmitate metabolism in vivo was impaired in THP-treated rats and the livers showed mixed steatosis. Steady-state mRNA levels of the carnitine transporter rat OCTN2 were increased in THP-treated rats in skeletal muscle and small intestine. In conclusion, THP inhibits butyrobetaine hydroxylase competitively, blocks carnitine biosynthesis in vivo and interacts competitively with renal carnitine reabsorption. THP-treated rats develop systemic carnitine deficiency over three weeks and can therefore serve as an animal model for human carnitine deficiency.

Animals↗
PubMed2000

Syndecan-1 expression is up-regulated in pancreatic but not in other gastrointestinal cancers.

Syndecan-1 belongs to the syndecan family of cell surface transmembrane heparan-sulfate proteoglycans, which participate in cell proliferation, cell migration and cell-matrix interactions. Decreased expression of syndecan-1 has been observed in some gastrointestinal malignancies, and it is thought that high levels of syndecan-1 correlate with the maintenance of epithelial morphology and inhibition of invasiveness. In our study, we characterized the expression of syndecan-1 in normal, chronic pancreatitis and primary and metastatic human pancreatic cancer tissues, in cultured pancreatic cancer cell lines and in esophageal, gastric, colon, and liver cancers. Pancreatic cancer cell lines expressed syndecan-1 mRNA and protein at variable levels. In addition, these cells also released syndecan-1 into the culture medium. Pancreatic cancer tissues markedly over-expressed syndecan-1 mRNA in comparison with both chronic pancreatitis (2.4-fold increase, p < 0.01) and normal pancreatic samples (10.6-fold increase, p < 0.01). There was no difference in syndecan-1 mRNA expression between early and advanced tumors. By in situ hybridization and immunohistochemistry, syndecan-1 expression was evident at relatively low levels in the ductal cells and less frequently in acinar cells of the normal pancreas. In chronic pancreatitis, syndecan-1 was present at low to moderate levels in areas with atrophic acinar cells and ductular complexes. In contrast, in pancreatic cancer tissues, syndecan-1 was present at moderate to high levels in the majority of the cancer cells within the tumor mass and also in metastatic lesions of pancreatic tumors. Syndecan-1 mRNA levels in other gastrointestinal malignancies (esophageal, gastric, colon and liver cancers) were not significantly different from the levels observed in the corresponding normal samples. Together, our findings suggest that syndecan-1 expression by pancreatic cancer cells may be of importance in the pathobiology of this disorder and that its role in pancreatic cancer seems to be different from that in other gastrointestinal malignancies.

Adenocarcinoma↗
PubMed2000

Epiregulin is Up-regulated in pancreatic cancer and stimulates pancreatic cancer cell growth.

Epiregulin belongs to the epidermal growth factor (EGF) family of polypeptides. Previous studies have underscored the important role of the EGF family of ligands and receptors in the pathology of pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). It is not known, however, whether epiregulin may also have a role in these diseases. Therefore, in the present study we investigated the expression and function of epiregulin in five pancreatic cancer cell lines and in PDAC and CP tissue samples. Epiregulin mRNA was present at high (MIA-PaCa-2 cells) or moderate levels (ASPC-1, CAPAN-1, and T3M4) in most cells, but was below detection levels in PANC-1 cells. All the cell lines exhibited a dose-dependent increase in growth in response to recombinant human epiregulin. Epiregulin mRNA levels were increased 2.1-fold in PDAC samples (P < 0.01) and 1.7-fold in CP samples (P < 0.01), when compared with the normal controls. There was no correlation between epiregulin mRNA levels and tumor stage or grade. By in situ hybridization, a moderate to intense epiregulin mRNA signal was present in most pancreatic cancer cells in PDAC. In contrast, only a weak (normal pancreas) to moderate (CP) signals were present in the ductal and acinar cells in CP. These findings suggest that epiregulin may contribute to the pathobiology of PDAC, and may also have a role in CP.

Adenocarcinoma↗
PubMed2000

Enhanced expression of Silencer of death domains (SODD/BAG-4) in pancreatic cancer.

Pancreatic cancers are resistant to TNF-alpha-mediated apoptosis. Silencer of death domains (SODD) binds to TNF-alpha receptor TNFR-1, and prevents spontaneous self-association of death domains and inappropriate receptor signaling. In addition, overexpression of SODD suppresses TNF-alpha-induced cell death. In this report, we demonstrate increased SODD mRNA levels in pancreatic cancer (n = 30) in comparison to normal control tissues (n = 20, P < 0.01). In situ hybridization analysis revealed SODD expression predominantly in the cancer cells within the pancreatic tumor mass. In contrast, SODD mRNA levels were not different (P > 0.05) in four other gastrointestinal cancers (liver, esophagus, stomach, colon) compared with the corresponding normal tissues. These findings indicate that in contrast to other gastrointestinal malignancies, in pancreatic cancer SODD might block TNF-alpha-mediated apoptosis which may influence the growth of pancreatic cancer cells.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Successful hepatic grafting after partial portal vein ligation in the rat: complete reversal of hemodynamic abnormalities.

BACKGROUND: Partial portal vein ligation (PPVL) is an established approach in the study of prehepatic portal hypertension in animals. The effect of orthotopic liver transplants (OLT) on hemodynamics in PPVL animals has not been investigated to date. The aim of this study was to develop a model of OLT in PPVL rats and to investigate its hemodynamic consequences. METHODS: Three groups of male Lewis rats were investigated (1) control animals (n=7), (2) PPVL (n=9), and (3) PPVL/OLT (n=16). Three weeks after PPVL, 9 animals were taken for hemodynamic measurements. OLT was performed in the remaining 16 PPVL rats (PPVL/OLT), and, 4 weeks later, hemodynamic measurements were made. Blood biochemical analysis was performed at different time points in all 3 groups. RESULTS: The PPVL animals presented with hyperdynamic systemic circulation, extensive collateral vascularization in the hilar region, and portal-systemic shunting (portal systemic shunting; 35.3+/-5.5%). In the PPVL/OLT group, 15 rats survived for 4 weeks (survival: 93.8%, 15 of 16). Of these PPVL/OLT rats, 3 died during the blood sampling protocol. In 3 PPVL/OLT rats, abnormal liver function and histology were found and deranged systemic and hepatic hemodynamics persisted after OLT. In the remaining 9 PPVL/OLT rats, systemic and hepatic hemodynamics had returned to normal at 4 weeks and portal systemic shunting was markedly reduced (2.5+/-0.9%). Liver function was in the normal range. CONCLUSIONS: (1) The possibility of performing OLT in PPVL rats with a high rate of survival has been confirmed. (2) In the majority of cases, complete reversal of hemodynamic abnormalities in the PPVL animals occurs after OLT (3). PPVL/OLT represents a new and important model in OLT research.

Animals↗
PubMed2000

Indolocarbazoles exhibit strong antiviral activity against human cytomegalovirus and are potent inhibitors of the pUL97 protein kinase.

We have analyzed a panel of protein kinase inhibitors (PKIs) and found that some indolocarbazoles (Gö6976, K252a, K252c) proved to be highly effective inhibitors of GCV-sensitive and -resistant human cytomegalovirus (HCMV) strains, but did not show any effect against herpes simplex virus. Antiviral activity was determined by focus reduction assays (IC(50) ranging from 0.009 to 0.4 microM). Other inhibitors of serine/threonine kinases (Gö6850, H-7, roscovitine) were found to be ineffective. Virus yield at 5 days after infection was reduced by three orders of magnitude with nanomolar concentrations of the indolocarbazoles. These compounds were fully effective when added up to 24 h post infection and showed reduced activity up to 72 h post infection. Cytotoxicity assays in proliferating and non-proliferating cells demonstrated that the effective antiviral concentration of these compounds was significantly lower than either antiproliferative (IC(50)/CC(50) ranging from 6.5 to 390) or cytotoxic (IC(50)/CC(50) ranging from 72. 5 to 1000) doses. The effects of PKIs on the virus-encoded protein kinase pUL97 were studied using recombinant vaccinia viruses. Indolocarbazoles strongly inhibited both pUL97 autophosphorylation (IC(50) ranging from 0.0012 to 0.013 microM) and pUL97-dependent ganciclovir phosphorylation (IC(50) ranging from 0.05 to 0.26 microM). Other inhibitors of serine/threonine kinases showed only weak (Gö6850) or no (H-7, roscovitine) effect on these pUL97 functions, while oxoflavone tyrosine kinase inhibitors had no effect at all.

Antiviral Agents↗
PubMed2000

Hepatic artery embolisation with a novel radiopaque polymer causes extended liver necrosis in pigs due to occlusion of the concomitant portal vein.

BACKGROUND/AIM: In an attempt to overcome some of the problems encountered with the materials available for liver embolisation, we investigated a novel radiopaque polymer of the polyurethane family (Degra-Bloc). METHODS: Hepatic artery embolisation of one liver lobe using polyurethane was performed in 19 healthy pigs. Microcirculatory changes were assessed by laser Doppler flowmetry. Radiological and pathological examinations of the livers, hearts and lungs removed provided information about the extent and effect of the embolisation. RESULTS: None of the pigs died due to hepatic failure or toxicity of polyurethane. Microcirculation of embolised liver lobes significantly decreased from 106 (+/-15) perfusion units (PU) to 45 (+/-6) PU immediately after embolisation and further to 28 (+/-7) PU before euthanasia. At this time conventional and angiographic X-ray controls demonstrated the radiopaque casts extending up to the peripheral arteries with signs of degradation over time but without formation of collateral vessels. The main pathological findings consisted of destruction of the portal tract structures and also of large areas of liver necrosis. Polyurethane was encountered in arterioles as small as 10-20 microm, but not in liver sinusoids, hearts or lungs. CONCLUSIONS: The novel polymer called DegraBloc is a biocompatible, slowly degradable, radiopaque embolic agent. The occlusion of the arterial tree up to the smallest arteriolar diameter combined with concomitant portal vein occlusion leads to sharp segmental necrosis in pig livers without formation of significant collaterals and without systemic embolism. In the treatment of liver tumours polyurethane might provide a promising alternative to conventional embolic materials, provided that it is used with care in patients with advanced liver cirrhosis.

Animals↗
PubMed2000

Liver nodules resembling focal nodular hyperplasia after hepatic venous thrombosis.

We report the case of focal nodular hyperplasia-like nodular hepatic lesions, that developed in the liver of a 35-year-old Caucasian female who required orthotopic liver transplantation for Budd-Chiari syndrome. The rapid development of focal nodular hyperplasia-like lesions in a severe hepatic vascular disorder and in the absence of cirrhosis may represent an additional argument in favor of the vascular origin of focal nodular hyperplasia. The pathogenesis of the nodules is not clear, but pathological arterialization of the liver in hepatic vein thrombosis may be a candidate mechanism.

Adult↗
PubMed2000

Connective tissue growth factor in human liver cirrhosis.

BACKGROUND: Connective tissue growth factor (CTGF) belongs to a family of factors that regulate fibrogenesis and wound healing. While the significance of transforming growth factor beta (TGF-beta) in liver fibrosis is well established, the role of CTGF in fibrosing hepatopathy is still unknown. METHODS: CTGF was analyzed in 10 normal and in 16 cirrhotic liver tissue samples. Northern blot analysis was used to examine the concomitant expression of CTGF and TGF-beta1 mRNAs, and the cellular localization of CTGF mRNA was studied by in situ hybridization. For identification of myofibroblasts and activated hepatic stellate cells, alpha-smooth muscle actin (alpha-SMA) immunohistochemistry was used. RESULTS: Northern blot analysis showed 6.5-fold enhanced expression of CTGF mRNA and 7.8-fold enhanced expression of TGF-beta1 mRNA in liver cirrhosis in comparison with normal controls (p<0.01). By in situ hybridization, CTGF mRNA was detectable in only a few spindle cells in the portal tracts in normal liver samples. In contrast, there was strong expression of CTGF mRNA in fibroblasts and myofibroblast-like cells present in fibrous septa surrounding the cirrhotic nodules, in stellate cells, in endothelial cells and in mesenchymal cells around ductular proliferations, and in ductular epithelial cells. There was a strong correlation between CTGF mRNA and TGF-beta1 mRNA as well as the degree of fibrosis (p<0.01). CONCLUSIONS: Overexpression of CTGF in liver cirrhosis, especially in fibroblasts/myofibroblasts and stellate cells, suggests that this novel factor may play an important role in hepatic fibrosis.

Actins↗
PubMed2000

Galectin-1 and galectin-3 in chronic pancreatitis.

Galectin-1 and galectin-3 have important functions in cell-cell interactions, cell adhesion to extracellular matrix, the organization of extracellular matrix, and tissue remodeling. To assess their potential role in chronic pancreatitis (CP), we examined their expression by Northern blot analysis, in situ hybridization, immunohistochemistry, and Western blot analysis in normal and CP pancreatic tissues. Northern blot analysis revealed a 4.5-fold increase of galectin-1 mRNA (p < 0.01) and a 3.8-fold increase of galectin-3 mRNA (p < 0.01) in CP samples compared with normal controls. In situ hybridization analysis of normal pancreas indicated low abundance of galectin-1 mRNA in fibroblasts, whereas galectin-3 mRNA was moderately present in ductal cells. CP samples exhibited moderate to intense galectin-1 mRNA signals in fibroblasts, whereas galectin-3 mRNA signals were intense in the cells of ductular complexes and weak in the degenerating acinar cells. In addition, intense galectin-1 and galectin-3 mRNA signals were present in nerves of normal and CP samples. Immunohistochemistry showed a distribution pattern of galectin-1 and galectin-3 similar to that described for in situ hybridization. Relative quantification of galectin-1 and galectin-3 protein by immunoblotting revealed an increase of 3.2-fold and 3.0-fold, respectively, in CP compared with normal controls. There was a significant correlation between galectin-1 and fibrosis and between galectin-3 and fibrosis and the density of ductular complexes. Up-regulation of galectin-1 in fibroblasts and galectin-3 in ductular complexes suggests a role of these lectins in tissue remodeling in CP. Galectin-1 might participate in ECM changes, whereas galectin-3 seems to be involved in both ECM changes and ductular complex formation.

Adult↗
PubMed2000

Surgical risk factors for condylar resorption after orthognathic surgery.

OBJECTIVE: The purpose of this study was to look for surgical risk factors for condylar resorption after orthognathic surgery. STUDY DESIGN: Seventeen patients of a group of 452 patients who had undergone orthognathic surgery consecutively and who were in accordance with the inclusion criteria of this study showed postoperative condylar resorption (group I). Preoperative cephalometric characteristics and surgically induced movements of this group were compared with a control group of 17 of 452 patients (group II) in whom postoperative condylar resorption and skeletal relapse did not develop, despite mandibular retrognathism (ANB angle >4 degrees) and high mandibular plane angle (>40 degrees). RESULTS: The kind of osteosynthesis used was not significantly different between the 2 groups. The amount of surgical advancements and the vertical movements of the jaws were not significantly different between the 2 groups. However, the distal (P =.005) and proximal (P =.007) mandibular segments were rotated significantly further counterclockwise in group I. Surgically induced posterior condylar displacement occurred significantly more frequently (P =.007) in group I. CONCLUSIONS: Counterclockwise rotation of the distal and proximal mandibular segments and surgically induced posterior condylar displacement seem to be important surgical risk factors for postoperative condylar resorption. Therefore, these movements seem to be contraindicated in patients who are at high risk.

Adolescent↗
PubMed2000

Macrophages infiltrating the tissue in chronic pancreatitis express the chemokine receptor CCR5.

BACKGROUND: The immunologic mechanisms involved in the development of chronic pancreatitis (CP) are poorly understood. Chronically inflamed tissues contain increased numbers of mononuclear cells expressing the CC chemokine receptor 5 (CCR5), which is also a coreceptor for HIV entry of macrophagetropic strains. However, whether this receptor is involved in the inflammatory process in CP is not known. In the current study, we analyzed the expression of CCR5 in CP. The detection of chemokine receptors on inflammatory cells would strongly suggest their involvement in the pathogenesis of CP (i.e., attraction and activation of these cells). To further evaluate this, we consecutively analyzed the expression of 2 ligands of CCR5: RANTES and MIP-alpha. METHODS: Pancreatic tissue samples of 22 patients with CP and of 7 healthy pancreas were evaluated. CCR5, RANTES, and MIP-1alpha were analyzed by Northern blot analysis. Consecutive tissue sections were stained for CCR5, CD3, and CD68 to define the leukocyte subtype expressing CCR5 in CP. RESULTS: By Northern blot analysis, CCR5, RANTES, and MIP-1alpha messenger RNA (mRNA) levels were 12.9-fold, 13.3-fold and 9.2-fold higher in CP specimens compared with healthy controls, respectively (P<.01). Immunostaining for CCR5 revealed a 30-fold increase of CCR5-positive cells in CP tissue compared with the healthy pancreas. Staining of consecutive tissue sections revealed that the majority of CCR5-positive cells were also CD68-positive (macrophages). CONCLUSIONS: Our data indicate that a remarkable portion of CCR5-positive cells in CP are macrophages. CCR5 is most likely involved in the attraction and activation of these macrophages, since the CCR5 ligands RANTES and MIP-1alpha are concomitantly upregulated.

Adult↗