A 6-fr guiding catheter (slim guide(®)) for use with multiple microdevices. An experimental study.

A modified technique is required in patients with wide-necked aneurysms whose treatment by the single microcatheter technique is difficult. We developed a 6-Fr guiding catheter (Slim Guide(®)) that features a large lumen (0.072 inch) for performing the modified technique. To evaluate the usefulness of Slim Guide(®) we carried out experiments using three types of 6-Fr guiding catheter. In experiment 1, the shaft hardness and kink resistance were compared among three different guiding catheters (Slim Guide(®), Launcher(®), Envoy(®)). In experiment 2, we inserted a microballoon catheter and a microcatheter into the three different guiding catheters and recorded the maximal infusion pressure. In experiment 3, we inserted 13 different types of microdevices into the three different guiding catheters and evaluated the resistance of the microdevices. Although the shaft of the Slim Guide(®) was softer than that of the other two guiding catheters, its kink resistance was comparable. The maximal infusion pressure was significantly lower than with Launcher(®) or Envoy(®) catheters. Furthermore, with Slim Guide(®), in 136 of 143 microdevice combinations examined (95.1%) there was no resistance; this was true for 125 (87.4%) and 116 (81.1%) combinations using the Launcher(®) - and the Envoy(®) guiding catheters, respectively. There was a significant difference between Slim Guide(®) and the other two guiding catheters with respect to their accommodation of double microsystems (p<0.05). Although the inner diameter of Slim Guide(®) is slightly larger than of the other two guiding catheters, it significantly increased the combination of microdevices that could be used for the coil embolization of difficult aneurysms.

Evaluation of dural arteriovenous fistulas with 4D contrast-enhanced MR angiography at 3T.

BACKGROUND AND PURPOSE: Four-dimensional contrast-enhanced MR angiography (4D-CE-MRA) at 3T may replace digital subtraction angiography (DSA) for certain diagnostic purposes in patients with intracranial dural arteriovenous fistula (DAVF). The aim of this study was to test the hypothesis that 4D-CE-MRA at 3T enables the same characterization of intracranial DAVFs as DSA. MATERIALS AND METHODS: The study population consisted of 18 consecutive patients with intracranial DAVFs (11 women, 7 men; age range, 35-82 years; mean age, 64.8 years). They underwent 4D-CE-MRA at 3T and DSA. The 4D-CE-MRA series combined randomly segmented central k-space ordering, keyhole imaging, sensitivity encoding, and half-Fourier imaging. We obtained 30 dynamic scans every 1.9 seconds with a spatial resolution of 1 x 1 x 1.5 mm. Two independent readers reviewed the 4D-CE-MRA images for main arterial feeders, fistula site, and venous drainage. Interobserver and intermodality agreement was assessed by kappa statistics. RESULTS: At DSA, 8 fistulas were located at the transverse sigmoid sinus; 8, at the cavernous sinus; and 2, at the sinus adjacent to the foramen magnum. Interobserver agreement was fair for the main arterial feeders (kappa = 0.59), excellent for the fistula site (kappa = 0.91), and good for venous drainage (kappa = 0.86). Intermodality agreement was moderate for the main arterial feeders (kappa = 0.68) and excellent for the fistula site (kappa = 1.0) and venous drainage (kappa = 1.0). CONCLUSIONS: The agreement between 4D-CE-MRA and DSA findings was good to excellent with respect to the fistula site and venous drainage.

Assessment of vascular supply of hypervascular extra-axial brain tumors with 3T MR regional perfusion imaging.

BACKGROUND AND PURPOSE: The vascular supply of extra-axial brain tumors provided by the external carotid artery has not been studied with RPI. The purpose of this work was to determine whether RPI assessment is feasible and provides information on the vascular supply of hypervascular extra-axial brain tumors. MATERIALS AND METHODS: Conventional ASL and RPI studies were performed at 3T in 8 consecutive patients with meningioma. On the basis of MRA results, we performed RPI by placing a selective labeling slab over the external carotid artery. Five patients underwent DSA before surgery. Two neuroradiologists independently evaluated the overall image quality, the degree of tumor perfusion, and the extent of the tumor vascular territory on conventional ASL and RPI. RESULTS: In overall quality of conventional ASL and RPI, no images interfered with interpretation. In comparisons of the vascular tumor territory identified by the conventional ASL and RPI techniques, the territories coincided in 3 cases, were partially different in 4, and completely different in 1. The interobserver agreement was very good (kappa = 0.82). In 5 patients who underwent DSA, the 4 patients in whom the dominant supply was the external carotid artery were scored as coincided or partially different. The 1 patient in whom the vascular supply was from the internal carotid artery was scored as completely different. CONCLUSIONS: RPI with selective labeling of the external carotid artery is feasible and may provide information about the vascular supply of hypervascular extra-axial brain tumors.

Prognostic value of perfusion MR imaging of high-grade astrocytomas: long-term follow-up study.

BACKGROUND AND PURPOSE: Although the prognostic value of perfusion MR imaging in various gliomas has been investigated, that in high-grade astrocytomas alone has not been fully evaluated. The purpose of this study was to evaluate retrospectively whether the tumor maximum relative cerebral blood volume (rCBV) on pretreatment perfusion MR imaging is of prognostic value in patients with high-grade astrocytoma. MATERIALS AND METHODS: Between January 1999 and December 2002, 49 patients (30 men, 19 women; age range, 23-76 years) with supratentorial high-grade astrocytoma underwent MR imaging before the inception of treatment. The patient age, sex, symptom duration, neurologic function, mental status, Karnofsky Performance Scale, extent of surgery, histopathologic diagnosis, tumor component enhancement, and maximum rCBV were assessed to identify factors affecting survival. Kaplan-Meier survival curves, the logrank test, and the multivariate Cox proportional hazards model were used to evaluate prognostic factors. RESULTS: The maximum rCBV was significantly higher in the 31 patients with glioblastoma multiforme than in the 18 with anaplastic astrocytoma (P < .03). The 2-year overall survival rate was 67% for 27 patients with a low (< or =2.3) and 9% for 22 patients with a high (>2.3) maximum rCBV value (P < .001). Independent important prognostic factors were the histologic diagnosis (hazard ratio = 9.707; 95% confidence interval (CI), 3.163-29.788), maximum rCBV (4.739; 95% CI, 1.950-11.518), extent of surgery (2.692; 95% CI, 1.196-6.061), and sex (2.632; 95% CI, 1.153-6.010). CONCLUSION: The maximum rCBV at pretreatment perfusion MR imaging is a useful clinical prognostic biomarker for survival in patients with high-grade astrocytoma.

Effect of bilateral subthalamic nucleus stimulation on levodopa-unresponsive axial symptoms in Parkinson's disease.

BACKGROUND: The levodopa responsiveness of motor, particularly axial symptoms is a good predictor of the effectiveness of subthalamic nucleus (STN) stimulation in patients with Parkinson's disease (PD). However, many Japanese PD patients are intolerant of higher doses of antiparkinsonian drugs and some aspects of their axial symptoms may remain unresponsive to treatment. We retrospectively investigated the effects of bilateral STN stimulation on the axial signs unresponsive to levodopa in Japanese patients with PD. METHODS: We enrolled 29 consecutive patients into this study. Six independent axial symptoms, i.e. falling, freezing, gait, standing, posture, and postural instability, were scored on the Unified Parkinson's Disease Rating Scale (UPDRS), before and 3 months after bilateral STN stimulation and differences were statistically analysed. FINDINGS: Postoperatively, the mean levodopa dosage was decreased by 27%. The preoperative responsiveness to antiparkinsonian drugs with respect to freezing, gait, posture, and postural instability were positively correlated with postoperative off-medication improvement (p < 0.05). For each individual axial symptom, some patients showed an excellent response to STN stimulation, despite preoperative unresponsiveness to levodopa. These selected patients were not always treated with lower doses of antiparkinsonian drugs preoperatively, but they had milder preoperative scores on the UPDRS with respect to daily activities and overall axial function. CONCLUSIONS: The axial symptoms of PD unresponsive to levodopa were ameliorated by bilateral STN stimulation in patients manifesting a milder degree of preoperative axial signs. Our findings suggest that STN stimulation exerted a definite but limited effect on levodopa-unresponsive axial features, pointing to the need to identify different target structures that control axial functions via non-dopaminergic systems.

Predictive assessment of shunt effectiveness in patients with idiopathic normal pressure hydrocephalus by determining regional cerebral blood flow on 3D stereotactic surface projections.

BACKGROUND: The regional cerebral blood flow (rCBF) and cerebral metabolism in patients with idiopathic normal pressure hydrocephalus (iNPH) remain to be studied in detail. PURPOSE: Using single-photon emission computed tomography (SPECT), we compared the characteristic rCBF patterns in iNPH patients who did, or did not, respond to shunt operations. MATERIALS AND METHODS: We studied 24 consecutive iNPH patients: 14 men and 10 women aged 68 to 88 years (mean 77.5 years). Using the Japanese normal pressure hydrocephalus grading scale, they were divided into responders and non-responders to shunt operations. Follow-up ranged from 10 to 36 months (mean 25 months). We obtained baseline single-photon emission computed tomography (SPECT) data on three-dimensional stereotactic surface projections (3D-SSP) before and after shunt operations, and compared rCBF in responders and non-responders. RESULTS: On statistical maps, responders manifested significantly lower rCBF in the basal frontal lobes and cingulate gyrus (anterior-dominant). CONCLUSIONS: The preoperative measurement of rCBF by 3D-SSP SPECT may help to identify iNHP patients expected to exhibit a good response to shunt operations.

Multiple peripheral middle cerebral artery aneurysms associated with Behcet's disease.

We report a 19-year-old woman with Behcet's disease who suffered a subarachnoid hemorrhage and had bilateral peripheral middle cerebral artery aneurysms. After steroid therapy for 3 days, the smaller aneurysm disappeared. The larger aneurysm was excised and the artery reconstructed using a superficial temporary artery graft. Histological examination showed vasculitis restricted to the wall of the aneurysm. This is the first report of arterial reconstruction for an aneurysm associated with Behcet's disease. Steroid therapy before the operation may facilitate repair of the arterial wall.

Pediatric primary CNS lymphoma: longterm survival after treatment with radiation monotherapy.

Primary central nervous system lymphoma (PCNSL) in childhood is very rare. We report a 5-year-old boy who presented with headache and nausea. Magnetic resonance imaging (MRI) showed a faintly enhanced lesion in the left cerebellar hemisphere. MRI-guided biopsy was returned with a histopathological diagnosis of lymphoma. Cranial radiotherapy alone with whole-brain irradiation (30 Gy) followed by a 20-Gy booster to the tumor bed was successful and the patient is alive, well, and in persistent complete remission 14 years post-treatment. This is the only pediatric PCNSL encountered at our institution between 1989 and 2004.

Diffusion-weighted imaging of metastatic brain tumors: comparison with histologic type and tumor cellularity.

BACKGROUND AND PURPOSE: On diffusion-weighted imaging (DWI), metastatic tumors of the brain may exhibit different signal intensities (SI) depending on their histology and cellularity. The purpose of our study was to verify the hypotheses (1) that SI on DWI predict the histology of metastases and (2) that apparent diffusion coefficient (ADC) values reflect tumor cellularity. MATERIALS AND METHODS: We assessed conventional MR images, DWI, and ADC maps of 26 metastatic brain lesions from 26 patients, 13 of whom underwent surgery after the MR examination. Two radiologists performed qualitative assessment by consensus of the SI on DWI in areas corresponding to their enhancing portions. We measured the contrast-to-noise ratio (CNR) on T2-weighted images and normalized ADC (nADC) values, and compared them with tumor cellularity. RESULTS: The mean SI on DWI and the CNR on T2-weighted images were significantly lower in well differentiated than in poorly differentiated adenocarcinomas and lesions other than adenocarcinoma. The mean nADC value was significantly higher in well differentiated than poorly differentiated adenocarcinomas and lesions other than adenocarcinoma. All 3 small-cell carcinomas and 1 large-cell neuroendocrine carcinoma exhibited high SI on DWI. The nADC value showed a significant inverse correlation with tumor cellularity. There was no significant correlation between the CNR and tumor cellularity. CONCLUSION: The SI on DWI may predict the histology of metastases; well differentiated adenocarcinomas tended to be hypointense, and small- and large-cell neuroendocrine carcinomas showed hyperintensity. Their ADC values reflect tumor cellularity.

Clinical evaluation of cellulose porous beads for the therapeutic embolization of meningiomas.

BACKGROUND AND PURPOSE: Cellulose porous beads (CPBs) are a new, exceptionally uniformly sized, nonabsorbable embolic agent. We evaluated their efficacy in the preoperative embolization of meningiomas. METHODS: In 141 consecutive patients, we used CPBs (200-microm diameter) for the preoperative embolization of meningiomas. We selected patients whose tumors were > or =4 cm with 50% of blood to the tumor supplied by the external carotid artery (ECA). All patients underwent a provocation test before embolization. The percentage of blood supplied to the tumor by the internal carotid artery and ECA was determined angiographically. Nonenhanced areas on postembolization MR imaging were calculated. Intraoperative blood loss, units of blood transfusion, and hemostasis at the time of surgery were recorded for each patient. The interval between embolization and surgery was intentionally longer than 7 days. RESULTS: Of the 141 patients, 128 underwent CBP embolization. Eleven patients had positive provocation test results, and 2 had vasospasm; they were not CBP embolized. In 72% of the patients CBP embolization achieved reduction in the flow of the feeding artery by more than 50%. The nonenhanced area on MR imaging was not significantly correlated with the degree of ECA supply or devascularization. The interval between embolization and surgery was 8-26 days (mean, 9.9 days). The longer this interval, the greater was the tumor-softening effect and the rate of tumor removal. CONCLUSIONS: CPBs may be useful for the preoperative embolization of meningiomas. To increase the efficacy of CPB embolization, the interval to surgery should be at least 7 days.

Expression of lymphocyte-specific chemokines in human malignant glioma: Essential role of LARC in cellular immunity of malignant glioma.

Lymphocytes are frequently observed in human malignant glioma, the mechanism(s) underlying their appearance is not fully understood. To clarify tumor immunity in malignant gliomas, we analyzed the expression of 8 novel lymphocyte-specific chemokines in human glioma cell lines and glioma tissues by RT-PCR, Northern blot, immunoblot and immunohistochemistry, and examined the correlation with the infiltration of various subsets of lymphocytes. For the 8 chemokines examined (LARC, TARC, ELC, SLC, PARC, LEC, HCC-2, and SCM-1alpha), expression of LARC was clearly detectable in all 12 glioma cell lines by RT-PCR. Additionally, expression of TARC and SCM-1alpha was detectable in the majority of glioma cell lines. However, the expression level of most chemokines was low, so that Northern blot analysis could not demonstrate their expression with the exception of LARC in 2 cell lines. Expression of LARC mRNA and LARC protein was strongly induced by phorbol myristate ester in U87 MG cells. The production of LARC protein was demonstrated in 4 of 8 glioblastoma tissues by immunoblotting, and 9 of 33 samples (27.3%) by immunohistochemistry. Interestingly, the positivity of LARC staining was significantly correlated with the infiltration of CD8-, CD4-, and CD45R0-positive cells (p<0.001). Although the constitutive expression level of LARC is low, certain stimulations could strongly induce its expression, and play a crucial role in the tumor immunity of human malignant glioma.

Are nonfunctioning pituitary adenomas extending into the cavernous sinus aggressive and/or invasive?

OBJECTIVE: We studied nonfunctioning pituitary adenomas extending to the cavernous sinus to gain insight into the discrepancy between their histologically benign nature and frequent extension into the cavernous sinus. METHODS: We studied 10 patients with nonfunctioning pituitary adenomas that completely encircled the cavernous carotid artery (extension group). All 10 patients underwent surgery to remove intrasellar and/or suprasellar parts of the adenomas. Ten patients with nonfunctioning pituitary adenomas without cavernous sinus extension comprised the control group. Tumor size follow-up data were obtained by magnetic resonance imaging. Immunostaining was performed for Ki-67, cathepsin B, and matrix metalloprotainase-9. To assess the wall thickness, 10 cavernous sinuses were removed from the cranial base of adult cadavers, and the walls were examined histologically. RESULTS: Magnetic resonance imaging demonstrated no remarkable growth in most of the patients during the follow-up period (mean, 65.8 mo). There was no statistical difference in Ki-67, cathepsin B, and matrix metalloprotainase-9 immunostaining between the extension group and the control group. The cadaver study demonstrated that the medial wall was significantly thinner than the superior and the lateral walls (P < 0.0005). We found small defects in the capsule histologically in 3 of 30 sections. CONCLUSION: Our results indicate that most of nonfunctioning pituitary adenomas extending into the cavernous sinus are neither aggressive nor invasive. The high incidence of cavernous sinus extension of benign adenomas may be caused by the weakness of the medial wall of the cavernous sinus.

Method for quantitatively evaluating the lateralization of linguistic function using functional MR imaging.

BACKGROUND AND PURPOSE: Various methods for evaluating the lateralization of linguistic function using functional MR imaging have been proposed. However, the optimal method remains controversial. The purpose of this study was not only to establish a method for quantitatively evaluating the lateralization of linguistic function but also to evaluate its optimality. METHODS: Internal speech tasks were measured by functional MR imaging in 17 healthy adult volunteers by use of z scores. The laterality index (LI) was calculated first by a previously reported method and second by our newly designed method, in which we investigated the correlation between the z scores and the number of activated pixels in the regions of interest; that is, we made scatter diagrams (z scores versus number of activated pixels). To obtain detailed information, we searched a regression function that fit the scatter diagrams well. RESULTS: We found the number of activated pixels was proportional to (1/z score)(4) and the correlation coefficient was very high. Each hemisphere showed an original proportional constant. Our newly designed LI was calculated from these two constants and was found to be a fixed value. In contrast, the reported LI varied with the z score. We found our LI differed in robustness and reproducibility from the reported LI. CONCLUSION: Our LI method proved more optimal than the reported LI. The lateralization of linguistic function can be evaluated quantitatively using our new LI method.

Phase II trial of pre-irradiation KRN8602 (MX2) in malignant glioma patients.

KRN8602 (MX2) is a newly developed morpholino anthracycline that crosses the blood-brain barrier where it becomes distributed in brain tissue after intravenous administration. This morpholino anthracycline has been found to be effective against human glioma cells and the intracerebrally transplanted tumors in vivo, We performed a phase II trial using KRN8602 as a single agent in malignant glioma patients who had not received prior adjuvant therapy. The 13 patients (5 glioblastomas, 7 anaplastic astrocytomas and 1 malignant oligodendroglioma) enrolled received at least 1 cycle of KRN8602 at 35 mg/m2/day in 3-4 week intervals by intravenous bolus. Ten of these patients could be evaluated for response, and 13 for toxicity. Three patients (1 glioblastoma and 2 anaplastic astrocytomas) demonstrated a complete response (3/10, 30%). Concerning side effects, myelosuppression was moderately severe, with 30.7% of patients developing grade 3 leukopenia. Severe nausea/vomiting was observed in 69% of the patients, however, cardiotoxicity was not observed. The results indicate that KRN8602 demonstrated modest activity against malignant glioma with relatively severe, but manageable toxicity. Further assessment of the efficacy and toxicity of KRN8602 against malignant glioma may be worthwhile.

Gene delivery with optimized electroporation parameters shows potential for treatment of gliomas.

Electroporation, a standard laboratory method of introducing exogenous molecules into cells, has been gaining importance as a very effective non-viral physical technique of gene delivery. In this study, we have used subcutaneous model of the C6 rat glioma cells and established an optimal condition to obtain very high gene expression in tumor tissues using both reporter and functional genes. Tumors grown on the flanks of Wistar rats are exposed and directly injected with plasmid DNA having the constructs of luciferase, green fluorescent protein and, the fragment of the diphtheria toxin, DT-A. The tumors are then subjected to square wave pulses from an electroporator. Gene expression is found to be several orders of magnitude higher when the tumors are pulsed with the optimized electrical parameters compared to the controls. For luciferase, the enhancement is approximately 135-fold, for the green fluorescent protein, gene expression is seen over a wide area within the sections examined, as contrast to a few punctate dots in the control specimens, and finally, DT-A shows massive death in the tumor tissue. A special circular array of six needles through which pulses are delivered with rotating electric field is found to be highly efficient in transferring genes inside the tumor. Direct injection of plasmid DNA followed by electroporation allows very high in vivo gene transfer and its subsequent expression into tumor tissues. This method may be applicable to any solid tumor.

Tissue factor expressed in pituitary adenoma cells contributes to the development of vascular events in pituitary adenomas.

BACKGROUND: Tissue factor (TF) was initially identified as an important factor in the initiation of coagulation. TF has recently been found to be expressed highly in certain types of malignant tumors. It has also been reported to be involved in systemic coagulopathy in cancer patients and in the proliferative and invasive activities of tumor cells. Tissue factor pathway inhibitor (TFPI) is a strong biologic inhibitor of TF. To the authors' knowledge, this is the first study of the expression of TF and TFPI in human pituitary adenoma. METHODS: The expression of TF and TFPI were analyzed by immunohistochemical methods in human pituitary adenoma samples. To examine whether TF and TFPI expression influence the proliferative and/or invasive character of pituitary adenomas, the authors determined the MIB-1 labeling indices and invasiveness of all the pituitary adenomas they examined. Furthermore, to determine whether TF contributes to coagulation inside adenoma tissues, the incidence of cysts or hematomas in adenomas was analyzed. RESULTS: In cells from 29 of 83 pituitary adenomas, overexpression of TF was observed. This was not the case for normal pituitary gland cells. TFPI was not expressed in either the adenomas or the normal pituitary glands from adenoma-bearing individuals. The expression of TF was significantly correlated with the formation of cysts or hematomas in pituitary adenomas. However, no such correlation with either the proliferative activity or the invasive character of the adenomas was observed. CONCLUSIONS: Locally overexpressed TF in adenoma cells may contribute to the development of vascular events, such as infarction and/or hemorrhagic infarction, in pituitary adenomas.

A synthetic selective inhibitor of factor Xa, DX-9065a, reduces monocyte chemoattractant protein-1 expression after ischemia-reperfusion injury in rat liver.

Activated factor X (FXa) is a trypsinlike serine protease involved in the cascade of blood coagulation. The monocyte chemoattractant protein-1 (MCP-1) may be important in the pathophysiology of liver ischemia-reperfusion injury. We investigated the effects of a selective FXa inhibitor, DX-9065a, on MCP-1 expression after ischemia-reperfusion in the rat liver. Liver ischemia was induced in rats by occluding the portal vein for 30 min. DX-9065a was injected intravenously 5 min before vascular clamping. Serum concentrations of MCP-1 were measured by enzyme-linked immunosorbent assay. The levels of MCP-1 mRNA in the liver after reperfusion were determined by northern blot analysis. In vitro MCP-1 production by peritoneal macrophages in response to alpha-thrombin was examined. Serum concentrations of MCP-1 increased and peaked at 6 hr after reperfusion. However, pretreatment of animals with DX-9065a resulted in significantly smaller increases in the serum concentration of MCP-1 after reperfusion in a dose-dependent manner. Pretreatment with DX-9065a significantly reduced MCP-1 mRNA levels in the liver after ischemia-reperfusion. In vitro MCP-1 production by peritoneal macrophages was enhanced by alpha-thrombin. In addition, DX-9065a significantly reduced tissue factor mRNA levels in peripheral monocytes after ischemia-reperfusion, compared to untreated animals. In conclusion, a selective inhibitor of FXa, DX-9065a, limited MCP-1 production after ischemia-reperfusion of the rat liver.

Loss of merlin-p85 protein complex in NF2-related tumors.

The NF2 tumor suppressor gene product, designated merlin, belongs to the family of molecules that links membranous protein with the cytoskeleton. We have previously shown that merlin was co-immunoprecipitated with a cellular protein, p85, in cultured cell. To analyze the alteration of merlin and associated proteins in surgical specimens, we developed a new method for biotin-labeling of whole cellular proteins. Screening of tumor tissues using our method showed that none of malignant gliomas and half of the NF2-related tumors had altered p85 and merlin. Our detection method seems useful for the screening of merlin alterations in NF2-related tumors.

Monocyte chemoattractant protein-1 enhances expression of intercellular adhesion molecule-1 following ischemia-reperfusion of the liver in rats.

Intercellular adhesion molecule-1 (ICAM-1) is important in neutrophil-dependent injury. We investigated the effects of monocyte chemoattractant protein-1 (MCP-1) produced by Kupffer cells on ICAM-1 expression after ischemia-reperfusion in rat liver by occluding the portal vein for 30 minutes. Serum concentrations of MCP-1 increased persistently. By Northern analysis, MCP-1 mRNA increased early and persisted. Kupffer cells harvested 6 hours after reperfusion also expressed this transcript. The transcript and protein also were produced by Kupffer cells from naive controls in response to reactive oxygen species. ICAM-1 mRNA transcripts increased, peaked 3 hours after reperfusion, and decreased gradually thereafter. The level of ICAM-1 mRNA transcripts in the WK-5 rat endothelial cell line were markedly enhanced by MCP-1. These results suggest that MCP-1 released by Kupffer cells early after ischemia-reperfusion modulates neutrophil-dependent tissue injury via ICAM-1.

Expression of PDGF, PDGF-receptor, EGF-receptor and sex hormone receptors on meningioma.

The expression of platelet derived growth factors (PDGF), the PDGF-Receptor (R) (alpha and beta types), epidermal growth factor (EGF)-Receptor (R) and sex hormone (oestrogen and progesterone) receptors was studied in 22 meningiomas. All tumours were PDGF-R beta type positive and 21 (95%) were PDGF positive. Only 2 (9%) were PDGF-R alpha type positive, 13 (59%) were EGF-R positive. The expression of these proteins was not related to the histological type or the malignancy of the meningiomas although the expression of PDGF and PDGF-R beta tended to be stronger in malignant meningiomas. Oestrogen and progesterone receptor protein were examined in 19 patients (10 females and 9 males). None of the meningioma cells revealed oestrogen receptor protein while 17 (89%) of the 19 meningiomas were positive for progesterone receptor protein. The expression of progesterone receptor was not related to histological type or malignancy. Our studies suggest that the autocrine system, through PDGF and PDGF-R type beta, may play an important role in the tumourigenicity of meningiomas. EGF-R was present in almost half and progesterone receptor in most of the meningiomas. There was no correlation between the expression of either PDGF, PDGF-R or EGF-R and the expression of progesterone receptor protein.