High-resolution magnetic resonance of the extracranial facial nerve and parotid duct: demonstration of the branches of the intraparotid facial nerve and its relation to parotid tumours by MRI with a surface coil.

AIM: To investigate the usefulness of high-resolution MR imaging in the evaluation of the extracranial facial nerve, compared with surgical findings. MATERIALS AND METHODS: Thirteen patients with benign parotid tumours were studied on a 1.5-T MR system with a 3 in circular surface coil. High-resolution T1-weighted spin-echo, T2-weighted fast spin-echo, and three-dimensional gradient-recalled acquisition in the steady state (GRASS) images were obtained in the axial planes. Oblique reformatted images were generated. Tumours, parotid ducts and facial nerves were identified on these images. The relationship of the tumours to the facial nerves was confirmed at surgery. RESULTS: Facial nerves appeared as linear structures of low intensity on all pulse sequences. The main trunks and cervicofacial and temporofacial divisions of the facial nerves were identified in 100%, 84.1% and 53.8% of GRASS images, respectively. Parotid ducts appeared as structures of low intensity on T1-weighted (66.6%) and GRASS images (81.8%), and as structures of very high intensity on T2-weighted images (91.7%). The relationships of the tumours to the facial nerves were correctly diagnosed in 11 (91.7%) of 12 cases. CONCLUSION: High-resolution MR imaging depicts the extracranial facial nerve and the parotid duct, and is useful for preoperative evaluation of parotid gland tumours.

Angiotensin II type 2 receptor mediates vascular smooth muscle cell apoptosis in cystic medial degeneration associated with Marfan's syndrome.

BACKGROUND: Cystic medial degeneration (CMD) is a histological abnormality that is common in the aortic diseases associated with Marfan's syndrome (MFS). Although little known about the mechanism underlying CMD, several recent reports have demonstrated that vascular smooth muscle cell (VSMC) apoptosis could play a substantial role in CMD. On the other hand, angiotensin II (Ang II) has been reported to play an important role in the regulation of VSMC growth and apoptosis via the Ang II type 1 receptor (AT1R) and type 2 receptor (AT2R). METHODS AND RESULTS: To elucidate the role of Ang II signaling via the Ang II receptors in CMD, we investigated AT1R and AT2R mRNA expression and tissue concentration of Ang II in MFS aortas (n=10) and control aortas (n=12). Furthermore, we examined the effects of an ACE inhibitor, an AT1R blocker, and an AT2R blocker on serum deprivation-induced VSMC apoptosis by organ culture system. AT1R expression was significantly decreased (P<0.01) and AT2R expression was significantly increased (P<0.001) in MFS aortas compared with control aortas, and tissue Ang II concentration was significantly higher in CMD than in the control condition (P<0.01). Both the ACE inhibitor and AT2R blocker significantly inhibited serum deprivation-induced VSMC apoptosis (P<0.05), although the AT1R blocker did not inhibit apoptosis in cultured aortic media from MFS patients. CONCLUSIONS: Accelerated ACE-dependent Ang II formation and signaling via upregulated AT2R play a pivotal role in VSMC apoptosis in CMD, and the ACE inhibitor could have clinical value in the prevention and treatment of CMD.

Congestive heart failure after peripheral blood stem cell transplantation: role of cytokines.

A 32-year-old woman was admitted with the diagnosis of congestive heart failure (CHF) without organic heart disease after peripheral blood stem cell transplantation (PBSCT) for malignant lymphoma. Various cytokines have been reported to be released from stem cells after PBSCT and some have a suppressive effect on myocardial contractility; elevated levels of cytokines have been reported in dilated cardiomyopathy (DCM) and/or CHF patients. In the present case, elevated levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha) were observed, and there was a parallel relationship between the recovery of cardiac function and the decrease of these cytokines, strongly suggesting that the release of IL-6 and TNF-alpha after PBSCT might have been important in the pathogenesis of the CHF.

Desmoid-type infantile fibromatosis in the mandible: a case report.

A 3-year-old boy with desmoid-type infantile fibromatosis arose in the mandible was reported. He was referred to our hospital because of suspected malignant bone tumor of the mandible. Histological examination of an open biopsy specimen was performed followed by tumor resection with marginal mandibulectomy and reconstruction by iliac bone grafting, which caused no functional complications nor mandibular deformity. To treat tumors in the facial skeleton, the surgical procedure should be planned based on the histological diagnosis in order to determine the proper area of resection to prevent functional or cosmetic complications. Especially in children, attention should be taken for benign but clinically resembling malignant rare diseases such as desmoid-type infantile fibromatosis.

[Risk factors and effect of reperfusion therapy on left ventricular free wall rupture following acute myocardial infarction].

Reperfusion therapy is one of the most effective treatments for acute myocardial infarction, but the effect on left ventricular free wall rupture remains to be determined. This study tried to clarify the risk factors and effect of reperfusion therapy on the risk of free wall rupture following acute myocardial infarction. 2,671 consecutive patients with acute myocardial infarction admitted to our hospital were examined. Incidence of free wall rupture showed no degenerative change(0 to 5.8%; mean 2.1%). The 1,269 consecutive patients from 1985 to 1995 were examined closely to evaluate risk factors and the effect of reperfusion therapy on the risk of free wall rupture. Fourteen patients who underwent emergent coronary artery bypass surgery were excluded. Free wall rupture was found in 25 patients (2.0%). Multivariate analysis confirmed that high age(> or = 70 years) and first acute myocardial infarction were independent risk factors of free wall rupture (odds ratio 3.62, p = 0.003; odds ratio 7.69, p = 0.046, respectively). The incidence of free wall rupture in the conservative therapy group(n = 799) was 2.1%, successful reperfusion group(n = 373) was 0.5%, and unsuccessful reperfusion group(n = 83) was 7.2% with significant statistical differences(p < 0.01). There was no statistical difference between the direct percutaneous transluminal coronary angioplasty group(n = 84, 3.6%) and the thrombolysis group(n = 372, 1.3%). Successful reperfusion was the only independent factor in the reperfusion therapy group that reduced the incidence of free wall rupture(odds ratio = 0.07, p = 0.001). We conclude that reperfusion of the infarct-related artery and more intensive management of unsuccessful reperfusion is important to prevent free wall rupture following acute myocardial infarction.

Course of IL-1beta, IL-6, IL-8, and TNF-alpha in the middle ear fluid of the guinea pig otitis media model induced by nonviable Haemophilus influenzae.

To characterize the local response in acute otitis media, courses of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor (TNF)alpha in middle ear fluid (MEF) of the guinea pig otitis media model induced by nonviable Haemophilus influenzae were investigated with enzyme-linked immunosorbent assay (ELISA) kits. The IL-1beta concentration in H. influenzae-inoculated ears peaked 24 hours after inoculation. The IL-8 concentration was significantly higher in H. influenzae-inoculated ears than in controls 48 and 96 hours after inoculation. The TNF-alpha concentration in H. influenzae-inoculated ears had an initial peak 6 hours after inoculation and had significant late increases 48 and 96 hours after inoculation. The results suggest that IL-1beta and TNF-alpha were produced by middle ear mucosa in the early stage of the experiment by stimulation of bacterial inoculation, which caused subsequent inflammatory cell accumulation, and that IL-8 and TNF-alpha were produced in the late stage by accumulating inflammatory cells.

Cloning and characterization of developmental endothelial locus-1: an embryonic endothelial cell protein that binds the alphavbeta3 integrin receptor.

We have taken advantage of an enhancer trap event in a line of transgenic mice to identify a unique developmentally regulated endothelial cell locus (Del1). The protein encoded in this locus contains three EGF-like repeats homologous to those in Notch and related proteins, including an EGF-like repeat that contains an RGD motif, and two discoidin I-like domains. Del1 is shown to be a matrix protein and to promote adhesion of endothelial cells through interaction with the alphavbeta3 integrin receptor. Embryonic endothelial-like yolk sac cells expressing recombinant Del1 protein, or grown on an extracellular matrix containing Del1 protein, are inhibited from forming vascular-like structures. Expression of Del1 protein in the chick chorioallantoic membrane leads to loss of vascular integrity and promotes vessel remodeling. Del1 is thus a new ligand for the alphavbeta3 integrin receptor and may function to regulate vascular morphogenesis or remodeling in embryonic development.

Radiological findings of adenolymphoma (Warthin's tumor).

The radiological findings of adenolymphomas (Warthin's tumor) treated in six hospitals between 1985 and 1994 were compared with the operative and histological findings and the usefulness of the radiological examinations was evaluated. The total number of patients was 72. The mean age was 61.8 years; 61 were males and 11 were females. All tumors developed in the parotid gland. Tc-99m-pertechnetate salivary gland scanning was performed in 13 patients and an increased uptake of the isotope was observed in only six patients. Even if Tc-99m-pertechnetate salivary gland scanning does not reveal intense accumulation, this tumor should not be ruled out. By computed tomography (CT), ultrasonography (US), and magnetic resonance imaging (MRI), the margin of all tumors was evident; however, the contents of the tumor varied. The contents and multiplicity of the tumors were well demonstrated by MRI, which was found to be the most accurate imaging modality.

The role of cadherin-catenin-cytoskeleton complex in angiogenesis: antisense oligonucleotide of plakoglobin promotes angiogenesis in vitro, and protein kinase C (PKC) enhances angiogenesis through the plakoglobin signaling pathway.

Angiogenesis plays an important role in various diseases and conditions such as malignant tumor, wound healing, and atherosclerosis. Since cell-to-cell adhesion may play a key role in angiogenesis, we investigated the effect of the cadherin-catenin-cytoskeleton complex on angiogenesis in human umbilical vein endothelial cells (HUVECs). Immunofluorescence staining revealed that alpha-catenin, beta-catenin, and plakoglobin were concentrated at cell-cell contacts in HUVECs. Antisense oligonucleotide (AS-oligo), complementary to the region of human plakoglobin was dissolved in saline and applied to the media at 1 mM every 12 h for 4 days, and sense oligonucleotide (S-oligo) was used as control. HUVEC migration from an injury line was enhanced by AS-oligo. Interestingly, HUVECs migrated in line with S-oligo, and in a scattered fashion with AS-oligo. Tube formation on Matrigel occurred earlier with AS-oligo than with S-oligo. These findings indicate that plakoglobin inhibited HUVEC migration and tube formation (angiogenesis) by regulating cell-cell adhesion.

Functional activity of the CFTR Cl- channel in human myocardium.

The cyclic AMP (cAMP)-dependent chloride channel in the heart has been identified in various species as the cystic fibrosis transmembrane conductance regulator (CFTR). Although functional expression of the channel in the human atrium has been reported, we could not induce any cAMP-dependent chloride conductance in the atrial cells even with maximal cAMP stimulation, whereas the conductance could be induced in rabbit ventricular cells. To clarify the discrepancy between the results, we examined the level of CFTR mRNA expression in both conductance-positive (human colonic epithelium and rabbit ventricle) and -negative (human atrium) tissues. Total RNA samples prepared from these tissues were subjected to the reverse transcription-polymerase chain reaction (RT-PCR). While CFTR transcripts were amplified from the conductance-positive samples, no amplified products could be detected from the conductance-negative sample. A nested PCR performed on the RT-PCR products of the conductance-negative sample resulted in successful amplification of the transcripts, indicating that the level of the CFTR mRNA expression in human atrium is extremely low compared with that in colonic epithelium and rabbit ventricle. The same molecular results were observed in human ventricular tissues. A nucleotide sequencing of the amplified transcripts showed that exon 5 of the CFTR gene was not alternatively spliced in human atrium and ventricle, and both the exon 5 spliced and unspliced isoforms were expressed in rabbit ventricle, unlike the findings of previous reports. Our data suggest that the amount of CFTR expressed in human myocardium might be physiologically insufficient to activate detectable cAMP-dependent chloride conductance.

Evaluation of mastoid air cell system by three-dimensional reconstruction using sagittal tomography of the temporal bone.

The mastoid air cell system has been recognized as an important contributor to the pathophysiology of middle ear inflammatory diseases. Various methods of temporal bone imaging have been designed to investigate the correlation between middle ear disease and mastoid pneumatization. In this study, the mastoid air cell system was reconstructed three-dimensionally from sagittal tomographic images of the temporal bone on X-ray films, using a personal computer to evaluate the mastoid pneumatization in a total of 29 patients with chronic otitis media, adhesive otitis media, adhesive-type cholesteatoma, attic cholesteatoma and cholesterol granuloma, and in five normal subjects as controls. Reconstructed three-dimensional images of the mastoid air cell system and its volume were analyzed. The reconstructed images were helpful in recognizing the three-dimensional solid appearance of the mastoid air cell system. The volume of the reconstructed mastoid air cell system was significantly reduced compared with that in the controls in each of the patient groups. Mastoid pneumatization in the patients with adhesive-type cholesteatoma was significantly suppressed compared with that in the adhesive otitis media patients. Interestingly, the adhesive otitis media group showed cell development at the tip of mastoid process, whereas the group of adhesive-type cholesteatoma did not, suggesting a difference in the pathophysiology in the two diseases. We found that three-dimensional reconstruction of the temporal bone using sagittal tomographic images was useful in evaluating the state of mastoid air cell system development in individual cases and in investigating the pathophysiology in middle ear disease.

[Twenty-one cases of malignant tumor of the external auditory canal or middle ear].

Between 1982 and 1994, 21 patients with malignant tumors of the external auditory canal and middle ear were treated at the Department of Otolaryngology, Niigata University. Eleven patients with tumors of the external auditory canal and 10 tumors of the middle ear were registered. There were 9 males and 12 females, and their ages ranged from 10 to 80 years (median: 61). Otalgia, otorrhea or bloody otorrhea were the chief complaints of most patients with external auditory canal of middle ear tumors. Pathological examination revealed squamous cell carcinoma in 16 patients, adenoid cystic carcinoma in 3 patients, and basal cell carcinoma and rhabdomyosarcoma in 1 patient each. External auditory canal tumors were surgically excised, while radical mastoidectomy and subsequent irradiation were performed for the middle ear tumors. The five-year survival rate determined by the Kaplan-Meier method, was 77.8% for patients with external auditory canal tumors and 40% for those with middle ear tumors.

Cooperative interaction of GATA-2 and AP1 regulates transcription of the endothelin-1 gene.

Endothelin-1 (ET-1) is a 21-amino-acid vasoactive peptide initially characterized as a product of endothelial cells. Reporter gene transfection experiments have indicated that a GATA site and an AP1 site are essential for ET-1 promoter function in endothelial cells, and GATA-2 appears to be the active GATA factor which regulates ET-1 expression. To look for interactions between AP1 and GATA-2, transactivation experiments were performed with expression vectors encoding c-Jun, c-Fos, and GATA-2. Cooperativity between the AP1 complex and GATA-2 was observed as a synergistic increase in transcriptional activity of the ET-1 reporter plasmid. In addition, AP1 was able to potentiate the action of GATA-2 on reporter constructs lacking a functional AP1 site. In a similar fashion, GATA-2 was able to potentiate the action of AP1 despite deletion of the GATA site. Experiments with GATA-1 and GATA-3 expression vectors provided evidence that this capacity to interact with AP1 may be a characteristic of all GATA family members. Biochemical evidence for AP1-GATA interaction was provided by immunoprecipitation experiments. A GATA-2-specific antiserum was shown to immunoprecipitate in vitro-synthesized Jun and Fos protein from reticulocyte lysate. Also, antisera directed against Jun and Fos were able to immunoprecipitate from nuclear extracts a GATA-binding protein, indicating the association of AP1 and GATA proteins in vivo.

Neutrophil oxygen metabolite inhibition of cultured chinchilla middle ear epithelial cell growth.

Middle ear inflammation in acute bacterial otitis media is characterized by accumulation of neutrophils in middle ear effusion. Since neutrophils release products that may injure surrounding tissues, we studied the effect of neutrophil metabolic products on middle ear epithelial cells (MEECs) in vitro. Chinchilla MEECs were incubated with phorbol myristate acetate (PMA)-activated human neutrophils or with hydrogen peroxide (H2O2). Cell growth, which was measured by 3H-thymidine incorporation, was inhibited by activated neutrophils and by H2O2. Unstimulated neutrophils, PMA alone, and catalase alone did not affect the viability of MEECs. Catalase, an enzyme that reduces H2O2, partially blocked the inhibitory effect of activated neutrophils and completely blocked the inhibitory effect of H2O2. Inhibition of MEEC metabolism by neutrophil-reactive oxygen species may contribute to epithelial injury, which may prolong the middle ear inflammatory response and lead to chronic tissue damage.

Improvement of regional wall motion in medically treated myocardial infarction with single-vessel coronary artery disease.

Long-term changes in regional wall motion (RWM) following acute myocardial infarction (AMI) in 42 patients with uncomplicated single-vessel disease were examined retrospectively by repeat cardiac catheterizations. The first and second cardiac catheterizations were performed at an average of 28 days and 6.6 years after the onset of AMI, respectively. All 42 patients underwent first and second cardiac catheterizations without undergoing coronary artery bypass surgery or coronary angioplasty. Regional left ventricular functions were analyzed by the centerline method using a right anterior oblique left ventriculogram. The wall motion abnormality score (WMAS) was defined as [# chord below -2SD] x [mean SD chord below -2SD]. The improvement in the WMAS was more prominent in cases with an occluded infarct-related artery. Thus, we concluded that 1) RWM improves significantly with medical treatment in long-term follow-up in cases of uncomplicated AMI with single-vessel disease, and 2) the improvement of RWM is completed within the first few weeks after AMI in cases with a patent infarct-related artery.

Clinical usefulness of three-dimensional reconstruction of the temporal bone from CT scans in cholesteatoma cases.

The importance of computed tomography (CT) in analyzing temporal bone diseases has increased, and the ability to reconstruct the temporal bone structures in three dimensions from multiple CT films has been required. In order to facilitate the visualization of temporal bone structures, we tried reconstructing temporal bone CT images three-dimensionally using a personal computer, and evaluated the possibility of using three-dimensional CT images clinically. Temporal bone CT scan films from five cases of cholesteatoma and a case of otosclerosis as control were examined. Four temporal bone structures (temporal bone contour, middle ear, mastoid, and inner ear) and cholesteatoma, extracted from enlarged black and white CT films, were inputted to the personal computer. Data import and image reconstruction procedures were performed using commercially available software. Our results indicate that three-dimensional reconstructions contribute to visualizing temporal bone structures spatially, and to choosing surgical approaches in difficult cases, such as petrous bone cholesteatoma. In conclusion, three-dimensional reconstructions using a personal computer is useful in the diagnosis and treatment of cholesteatoma.

[Phase III trial of 99mTc-rhenium colloid for lymphoscintigraphy].

A multicenter study was carried out on 191 patients (196 examinations) with lymphatic system disorders to evaluate the efficacy and safety of 99mTc-rhenium Colloid, a tracer for lymphoscintigraphy (TCK-17). Local pain and swelling occurred at the site of injection in 79.6% and 5.1% of patients, respectively, and 2 patients experienced mild fever. The accuracy was calculated on the basis of the results obtained by other diagnostic methods. Lymphoscintigraphy using TCK-17 was sensitive diagnostic procedures, but low specificity. The efficacy was classified into five grades: "Excellent", "Good", "Moderate", "Equivocal", and "Poor". 67.3% of all examination were evaluated as "Excellent" or "Good". This study revealed TCK-17 was a useful radiopharmaceutical for lymphoscintigraphy because of its safety and effectiveness.

Role of the bacterial cell wall in middle ear inflammation caused by Streptococcus pneumoniae.

The pathogenesis of middle ear inflammation caused by Streptococcus pneumoniae was explored in the chinchilla model with different pneumococcal cell wall (CW) preparations, including isolated native CW, M1 muramidase CW (M1-CW) digest, amidase CW digest, and M1 peptidoglycan (M1-PG) digest. Inflammatory cell and lysozyme concentrations in middle ear fluid (MEF) were measured between 6 and 72 h after the middle ears were inoculated with one of the preparations or sterile saline. Middle ear histopathology was measured quantitatively at 72 h. Native CW, M1-CW digest, and amidase-CW digest caused significantly more inflammatory cell influx and lysozyme accumulation in MEF than saline did. M1-PG digest also caused more inflammatory cell influx and lysozyme accumulation in MEF than saline did but caused less inflammation than native CW or either CW digest. Epithelial metaplasia was significantly greater in ears inoculated with native CW than in ears inoculated with the CW or PG digest or with saline. Pneumococcal CW is, therefore, the principal factor that initiates middle ear inflammation in acute pneumococcal otitis media, and CW teichoication seems to be important in initiating this response.

The synthesis of cyclopropano nucleosides.

A tricyclic, fused cyclopropano nucleoside 8 containing a ketal group was synthesized by the one-pot seven sequential reactions of a trimesylated allofuranosyl adenine derivative 6 with Mg(OMe)2. When KOH was used instead of Mg(OMe)2, an alpha, beta-unsaturated ketonucleoside 7 was obtained.