Expression of the c-erbB-2-encoded oncoprotein and progesterone receptor in human meningiomas

The present study investigated the expression of c-erbB-2 in 59 meningiomas, including different histological subtypes and anaplastic variants, by immunocytochemistry and molecular biological techniques. Immunohistochemistry using the monoclonal antibody FWP-51 directed against c-erbB-2-encoded oncoprotein gp185 demonstrated variable degrees of immunoreactivity in all meningiomas. The intensity of immunostaining correlated with the degree of expression as assessed by Western analysis in 28 meningiomas using polyclonal antiserum 21N. There was no correlation between the degree of expression and histological variants. Immunoreactivity of all menigiomas was distinctly less intense, however, than that of the human breast cancer cell line SK-BR-3, and slightly lower than that of brain metastases of breast and ovarian carcinomas that served as positive controls for both methods. By Southern analysis all meningiomas showed a single copy of the c-erbB-2 gene. Non-neoplastic arachnoid cap cells also exhibited c-erbB-2 expression and the degree of immunoreactivity was comparable with the majority of meningiomas. These data argue against an overexpression of c-erbB-2 in meningiomas, but rather indicate a cell-type-specific constitutive expression of the c-erbB-2 gene product in meningiomas and their putative progenitor cells. Since a subgroup of meningiomas is known to express progesterone receptors (PR), gp185 immunoreactivity was compared to the hormone receptor status using monoclonal antibody KD68. Fifty-six percent meningiomas showed PR immunoreactivity, but there was no statistically significant correlation with the degree of gp185 expression.This study was supported by a grant of the Tumorzentrum Heidelberg/Mannheim (M.K., No. 10028060)     

18F-FDG PET for detecting myocardial viability: validation of 3D data acquisition.

(18)F-FDG PET is an important diagnostic tool for detecting myocardial viability in patients with coronary artery disease. In combination with perfusion scanning, (18)F-FDG PET allows differentiation between reversibly and irreversibly damaged myocardium and selection of patients likely to benefit from revascularization. Viability PET is usually performed in two-dimensional (2D) mode. Taking into account the rising number of three-dimensional (3D)-only scanners, a validation of 3D acquisition is required. METHODS: Twenty-one patients with coronary artery disease referred for (18)F-FDG PET underwent an imaging protocol of nongated 2D (2D-NG) and gated 2D (2D-G) acquisitions for 15 min each, followed by 3D gated acquisitions for 10 min (3D-10) and 5 min (3D-5), using an ECAT Exact HR+ scanner. Results were analyzed using a 20-segment polar map in terms of activity concentration (Bq/mL), viability (50% uptake threshold), regional activity distribution, visual assessment of viability based on a 3-point rating scale, and left ventricular ejection fraction. RESULTS: Activity concentration measured in each segment with 2D-G, 3D-10, and 3D-5 showed a good linear correlation with 2D-NG. Quantitative viability assessment with 3D-5 gave a sensitivity of 84% and a specificity of 98%, compared with 2D-NG. No differences in regional activity distribution and visual viability assessment were found between the various protocols. Left ventricular ejection fractions obtained with 3D-10 and 3D-5 showed a good linear correlation with those measured with 2D-G. CONCLUSION: An ECG-gated 3D imaging protocol gave results comparable to those of 2D acquisition with regard to absolute and regional myocardial activity distribution, left ventricular function, and visual viability assessment. Sensitivity for viability assessment with a 50% uptake threshold was significantly less with 3D, but specificity was maintained. This protocol delivers a clinical performance nearly equivalent to that of 2D acquisition.     

Periodontal status of a subject sample of Yemen

Abstract From August to October 1991, the periodontal status of 1001 Yemenis representing the age groups 12-14, 15-19, 20-24 and 35-44 years was recorded and evaluated with preference to the CPITN, the calculus index and clinical attachment levels. The impact of chewing khat, the leaves of a cultivated, alkaloid shrub, and of using the traditional miswak chewing stick for oral hygiene purposes were investigated. The results show that 6.9% of the juvenile probands (15-19 years) had healthy periodontal tissue (CPITN 0). whereas bleeding on probing and calculus (CPITN 1+2) were registered in 86.2%. In the 35-44 year age group. 1.7% were periodontally healthy, whereas 84.5% displayed plaque retention or shallow pocketing (CPITN 2-3) and 12.5% deep pocketing (CPITN 4). The treatment needs in all age groups are confined primarily to calculus removal and instruction in oral hygiene. The clinical attachment level and the calculus index revealed age-related attachment loss and calculus formation, primarily among male probands. The higher khat consumption among the male population is reflected in its detrimental effect on the periodontal tissue, especially among younger probands. Oral hygiene aids have also an influence on periodontal status, with a toothbrush proving more efficient than the miswak. WHO efforts directed towards prophylactic programs need to be intensified but can be staffed by dental hygienists.     

Successful heart-lung transplantation in a patient with kyphoscoliosis.

The association is well established between congenital heart disease and spinal deformities such as scoliosis or kyphosis, but data are not available for risks and the outcome of heart surgery in patients with spinal deformities. We report a case of successful orthotopic heart lung transplantation in a patient with complex congenital heart disease and severe chest deformity who had undergone previous spinal fusion surgery for progressive right convex thoracic kyphoscoliosis.     

A method to remove artifacts in attenuation-corrected myocardial perfusion SPECT Introduced by misalignment between emission scan and CT-derived attenuation maps.

Nonuniform soft-tissue attenuation affects the diagnostic accuracy of SPECT in myocardial perfusion imaging. The attenuation map required for attenuation correction can be acquired using x-ray tomography (CT). Frequent findings in attenuation-corrected images are defects in the apical and anterior myocardial wall. We assume that these are artifacts produced by misalignment of SPECT images and the attenuation map. METHODS: One hundred forty patients underwent myocardial perfusion imaging with 99mTc-methoxyisobutylisonitrile. Twenty-seven of 140 showed pronounced defects in the apical or anterior wall only after CT-based attenuation correction. SPECT and corresponding CT slices were examined for misalignment in the ventrodorsal direction (y-direction) visually and by threshold-based delineation of the body surface. Mismatched studies were realigned and image reconstruction and analysis were redone. The effect of the correction was assessed visually and by semiquantitative analysis based on a 20-segment model using 4D-MSPECT. RESULTS: In 15 of 27 patients, the improved coregistration led to smaller and less-pronounced defects in the regions mentioned. In 6 of 27 patients, former defects were judged as normal. No improvement was seen in only 4 patients. In these 4 subjects, the mismatch in the y-direction was <1 pixel (7 mm), and visual inspection suggested a coincident mismatch in the craniocaudal direction. In 2 cases, coregistration was not possible because the body outline extended beyond the CT field of view. Semiquantitative analysis revealed a significant increase of the relative uptake in the apex; in the apical segments of the anterior, septal, and inferior wall; and in the mid-anterior and mid-anteroseptal segment. Basal segments of the anterolateral, lateral, and inferolateral wall and the middle inferolateral segment showed a significant decrease of relative uptake. CONCLUSION: Misalignment in the y-direction between SPECT and the attenuation map can lead to artifacts in the apical, septal, and anterior wall, which will appear as defects. It also can cause overcorrection in the basal inferior and lateral segments. There is evidence that mismatches along the other directions may have a similar effect. The coregistration of SPECT and the attenuation map needs to be verified for every patient, even when using integrated dual-modality imaging devices.     

Effects of hepatic arterial yttrium-90 microsphere administration alone and combined with regional bromodeoxyuridine infusion in dogs

Brachytherapy by embolization with radiotherapeutic microspheres following intraarterial infusion of a radiosensitizer represents an attempt to combine several selective modalities into a more potent, focused attack on regionally confined tumors. In pursuit of this goal, we examined the ability of foxhounds with surgically implanted hepatic arterial (HA) delivery systems to tolerate a clinically relevant dosage of HA yttrium-90 (Y-90) by microsphere administration either alone or preceded by a 28-day constant HA infusion of either 5-bromo-2'-deoxyuridine (BUDR) or a control solution. Five dogs received BUDR (10 mg/kg/day) and five a control buffer infusion for 28 days immediately prior to the administration of Y-90-coated 15 micron resin microspheres (equivalent of 5000 rads to the entire liver) to each dog on day 31. In all animals, blood counts, bilirubin, amylase, appetite, weight, and behavior remained unchanged. Dogs receiving the microspheres after buffer infusion alone exhibited no hepatic enzyme alanine aminotransferase or alkaline phosphatase elevation. Alanine aminotransferase and alkaline phosphatase levels both rose during the third week of BUDR infusion, and while subsequent microsphere administration further increased enzyme levels, these levels had largely normalized by necropsy on day 82. At necropsy, the type and degree of hepatic toxicity among the animals receiving radioactive microspheres was comparable to that previously described in patients receiving external beam hepatic irradiation at conventional doses (2000-3000 rads). Also noted was a radiation-induced cholecystitis (due in large part to the gallbladder's total reliance on the hepatic artery for blood supply). One resin microsphere dog exhibited a small quantity of microspheres in the lungs causing focal radiation-induced granulomas suggesting the need to assess shunting of microspheres through the liver in clinical studies. Thus, HA Y-90 microspheres with BUDR can produce acceptable, nonlethal, and tolerable toxicities in this dog model suggesting that clinical studies of this combination are not likely to be contraindicated by synergistic toxicity. Although HA BUDR did not contribute significantly to the toxicity of the Y-90 microspheres, HA BUDR by itself administered uninterrupted for 4 weeks may, like HA FUDR (clinically), cause chemical hepatitis/cholangitis. The unexpected fragmentation of the resin spheres (albeit without myelosuppression) has led us to begin studies with a recently developed nondisruptible glass microsphere (ThereSphere) in which the Y-90 is part of the glass matrix and cannot leach.(ABSTRACT TRUNCATED AT 400 WORDS)     

Preparative HPLC purification of prostaglandin endoperoxides and isolation of novel cyclooxygenase-derived arachidonic acid metabolites

A preparative HPLC purification scheme for the isolation of prostaglandin endoperoxides prepared by short-time incubation of [1-14C]-labelled arachidonic acid (AA) with sheep seminal vesicle microsomes was developed. Milligram quantities of prostaglandin G2 (PGG2) and prostaglandin H2 (PGH2) were obtained in greater than or equal to 95% purity within shortest time. Furthermore, careful application of this HPLC technique led to the isolation of two minor [1-14C]-labelled fractions which according to their spectral and chromatographic characteristics, were identical with 15(S)-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) and 15(S)-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE). Another HETE substituted at either C11 or C12 was also present. The formation of these products was mediated by cyclooxygenase as evidenced by aspirin (100 microM) and indomethacin (10 microM) inhibition. Sulfhydryl-blocking agents such as p-hydroxymercuribenzoate (1 mM) and/or the 12-lipoxygenase inhibitor esculetin (100 microM) were without effect. In addition to these AA metabolites four other fractions contained arachidonate-derived endoperoxides with antiaggregatory properties, all of which released malondialdehyde upon incubation with thromboxane A2 synthase. No thromboxane formation was observed although turnover numbers were comparable to those of PGG2 and PGH2. The formation of these endoperoxides did not occur via enzymatic or non-enzymatic degradation of PGG2 or PGH2. The exact chemical nature of these endoperoxides remains to be established.     

Enhanced in vitro proliferation and in vivo tumorigenic potential of mammary epithelium from BALB/c mice exposed in vivo to gamma-radiation and/or 7,12-dimethylbenz[a]anthracene

Virgin female BALB/c mice were exposed in vivo to whole body gamma-radiation and/or to 7,12-dimethylbenz[a]anthracene (DMBA) p.o. Mammary epithelial cells were isolated and assayed for carcinogen altered cell populations both in vitro by an epithelial focus assay and in vivo by injection into cleared fat pads of syngeneic host mice. Five groups of mice were exposed as follows: (a) sham controls; (b) 50-rad gamma-radiation; (c) 100-rad gamma-radiation; (d) 75 micrograms DMBA; or (e) 50-rad gamma-radiation followed in 1 week by 75 micrograms DMBA. Mammary epithelial cells were isolated and assayed at 24 h and at 1, 4, 16, and 52 weeks after in vivo exposure. Four to 12 mice per treatment per time point were individually assayed. Altered in vitro growth potential was characterized by the proliferation of carcinogen exposed (but not control) cells as epithelial foci which persisted at least 12 weeks in primary culture. Epithelial foci which could then be subcultured at least four times were termed subculturable epithelial foci. Altered in vivo morphogenic potential was characterized by dysplastic or neoplastic growth in host fat pads. With increased time in situ between exposure and assay, cell populations emerged which exhibited both increased in vitro subculturability and enhanced tumorigenic potential including a host response upon injection in vivo. Further, combined radiation and DMBA resulted in higher frequencies of subculturable epithelial foci than either treatment alone. The relevance of these progressive cellular changes to the process of mammary tumor development is discussed.