Meningiomas with disomy of chromosome 22: study of 9 cases

BACKGROUND: Cytogenetic studies of meningiomas suggest that loss of (or parts of) chromosome 22 is a primary event in the development of these tumors; later on, other chromosomal changes would occur in the caryotypes. All these secondary changes are observed mainly in cases with high clinical aggressivity. However, in a few cases of meningiomas disomy 22 coexists, but with other chromosomic anomalies. We present clinical, histopathological and cytogenetic findings in a group of meningiomas with disomy of chromosome 22. PATIENTS AND METHODS: We collected 10 meningiomas from nine patients which ages ranged between 28-70 years. Fresh tumoral specimens were divided for histologic examination and cytogenetic study, performed after short-term culture. RESULTS: At microscopic examination 5 tumors were classified as benign meningiomas, four as atypical and one as malignant meningioma. Four cases were recurrent tumors. The cytogenetic studies showed that all tumors presented two chromosomes 22 and other chromosome abnormalities. Losses in chromosomes 4, 7, 10, 14, 16, 17 and 20 were frequent; cytogenetics rearrangements of chromosomes 1, 4, 5, 7, 14, 19 and 22 were frequently involved. CONCLUSIONS: In karyotypic evolution of meningiomas, secondary anomalies of chromosomes 1p, 10 and 14 are the most common and appear to be associated with a more aggressive clinical course. In this group of meningiomas with disomy 22, these anomalies were also frequently found, and were related in 50% of cases with atypical or malignant morphologies and of them with recurrent tumors in the 40%.     

Outcome in general medical patients presenting with common symptoms: a prospective study with a 2-week and a 3-month follow-up

Human T-cell-mediated autoimmune diseases are often genetically linked to particular alleles of HLA class II genes. Vogt-Koyanagi-Harada's (VKH) disease, which is regarded as an autoimmune disorder in multiple organs containing melanocytes, has been found to be associated with HLA-DR4 (DRB1(*)0405) and HLA-DR53 (DRB4(*)0101). Tyrosinase is a melanoma antigen (Ag) expressed by normal melanocytes as well as melanoma cells against which responses by autologous T cells have been detected. We established a T-cell line from the peripheral blood of a patient with VKH disease which responded to synthetic peptides corresponding to tyrosinase. The T-cell line was generated which recognized the tyrosinase p188 - 208 peptide when presented by the HLA-DR4 (DRB1(*)0405) molecule on the surface of HLA class II-expressing L-cell transfectants. The minimal antigenic peptide which induced T-cell responses was an 11-amino-acid sequence and located at tyrosinase p193 - 203 (E-I-W-R-D-I-D-F-A-H-E). This peptide contained the DRB1(*)0405-binding peptide motif (hydrophobic residues (Y, F, W) at position 1 as an anchor residue, and negatively charged residues (D, E) at position 9), which corresponded to the W at p195 and the D at p203. These observations demonstrate that tyrosinase peptides are immunogenic, and may be a candidate for an autoantigen in VKH disease, suggesting that probing the T-cell responses against synthetic peptides is a productive approach for identifying the autoantigenic peptides associated with autoimmune diseases including VKH disease.     

Pneumococci stimulate the production of the inducible nitric oxide synthase and nitric oxide by murine macrophages

The role of nitric oxide (NO) in the pathophysiology of gram-positive sepsis is uncertain. In inflammatory conditions, high-output NO production is catalyzed by the enzyme inducible nitric oxide synthase (iNOS). The ability of 2 strains of pneumococci, pneumococcal cell wall preparations, and purified pneumococcal capsule (Pnu-Imune 23) to trigger the production of iNOS protein and NO in RAW 264.7 murine macrophages was tested. Live pneumococci, oxacillin-killed pneumococci, and pneumococcal cell wall preparations stimulated the production of iNOS and NO by RAW 264.7 cells in the presence, but not the absence, of low concentrations of recombinant murine interferon-gamma. In contrast, purified pneumococcal capsule induced little or no iNOS or NO production by these cells. Thus, pneumococci stimulate high-output NO production by murine macrophages. The potential role of NO in the pathogenesis of pneumococcal sepsis deserves further study.     

Substrate specificity of NO synthases: detailed comparison of L-arginine, homo-L-arginine, their N omega-hydroxy derivatives, and N omega-hydroxynor-L-arginine

A detailed comparison of the oxidation of five compounds closely related to L-arginine (Arg) by purified recombinant neuronal and macrophage NO synthases (NOS I and NOS II) was performed. Homo-L-arginine (homo-Arg) is oxidized by both NOSs in the presence of NADPH with major formation of NO and homo-L-citrulline, with a molar ratio of close to 1, and minor formation of N omega-hydroxyhomo-L-arginine (homo-NOHA). Oxidation of homo-NOHA by the two NOSs also leads to NO and homocitrulline in a 1:1 molar ratio. On the contrary, N omega-hydroxynor-L-arginine (nor-NOHA) is a very poor substrate of NOS I and II, which fails to produce significant amounts of nitrite. The catalytic efficiency of both NOSs markedly decreases in the order Arg > NOHA > homo-Arg > homo-NOHA, as shown by the 20- and 10-fold decrease of kcat/Km observed for NOS I and NOS II, respectively, when comparing Arg to homo-NOHA. The greater loss of catalytic efficiency for homo-Arg, when compared to that for Arg, appears to occur at the first step (N-hydroxylation) of the reaction. In that regard, it is noteworthy that the Vm values for NOHA and homo-NOHA oxidation are very similar (about 1 and 2 micromol of NO min-1 mg of protein-1 for NOS I and II, respectively). In fact, lengthening of the Arg chain by one CH2 leads not only to markedly decreased kcat/Km but also to clear disturbances in NOS functioning. This is shown by a greater accumulation of the N omega-hydroxyguanidine intermediate (homo-NOHA:homocitrulline ratio between 0.2 and 0.4) and an increased consumption of NADPH for NO formation (between 2.0 and 2.6 mol of NADPH consumed for the formation of 1 mol of NO in the case of homo-Arg, instead of 1.5 mol in the case of Arg). Most of the above results could be interpreted by comparing the possible positionings of the various substrates relative to the two NOS active oxygen species which are believed to be responsible for the two steps of the reaction.     

Cerebral emboli and serum S100beta during cardiac operations

BACKGROUND: The glial protein S100beta has been used to estimate cerebral damage in a number of clinical settings. The purpose of this investigation was to determine the correlation between cerebral microemboli and S100beta levels during cardiac operations. METHODS: Transcranial Doppler ultrasonography was used to measure emboli in the right middle cerebral artery. Emboli counts (n = 111) were divided into five time periods: (1) incision to aortic cannulation; (2) aortic cannulation to cross-clamp onset; (3) cross-clamp onset to cross-clamp release; (4) cross-clamp release to decannulation; and (5) decannulation to chest closure. The level of S100beta (n = 156) was measured at baseline, at the end of cardiopulmonary bypass, then 150 and 270 minutes after cross-clamp release. RESULTS: The level of S100beta correlated with age, cardiopulmonary bypass time, cross-clamp time, and number of emboli at time period 2. Although cardiopulmonary bypass time was univariately associated with S100beta level, it became nonsignificant in a multivariable model that included age and cross-clamp time. CONCLUSIONS: The correlation of S100beta level with emboli measured during cannulation (time period 2) supports the hypothesis that cannulation is a high-risk time period for cerebral injury.     

Approximation to conservative surgery of Leydig cell tumor

OBJECTIVES: To analyze the clinical and histological characteristics of 5 cases of Leydig cell tumor in order to establish the criteria for conservative surgical management. METHODS: Of 31 testicular tumors diagnosed from 1982-1993, 5(16.1%) were Leydig cell tumors. We analyzed patient general characteristics, the prevalent feminizing (60%) and hypogonadal features and the histopathological characteristics that might indicate a non aggressive course of the tumor. RESULTS: No metastasis was observed at 522.9 months mean follow up. Three patients underwent orchidectomy through the inguinal approach; one case had been incidentally discovered after subalbuginea resection due to a disseminated prostatic carcinoma and the fifth patient was treated conservatively by tumorectomy and is tumor-free at more than 120 months follow up. CONCLUSIONS: Parenchyma-sparing surgery may have a place in the treatment of interstitial cell tumor, with evident endocrinological and psychological benefits, especially in the young males that meet the clinical and histological criteria for conservative surgical management.     

Comparison of left anterior oblique, anterior, and geometric mean methods in gastric emptying assessment of postpancreaticoduodenectomy patients

Although left anterior oblique (LAO) gastric emptying studies appear to be an adequate alternative to geometric mean (GM) measurements in patients with normal gastric anatomy, it is not clear whether they can be used after gastric or duodenal surgery. In this study, dual-phase gastric emptying studies with combined solid-liquid meal were performed in 54 patients who had undergone pancreaticoduodenectomy (Whipple procedure). Gastric emptying was studied with GM, LAO, and anterior (ANT) methods. T1/2 and percent gastric retention at 10, 30, 60, 90, and 120 minutes were calculated. Results from the three methods were compared using correlation analysis and the t test. The t test showed no significant difference in T1/2 and percent retention values between the GM and LAO or ANT views. The solid emptying T1/2 showed a better correlation between GM and LAO values (r = 0.824) than between GM and ANT (r = 0.589). For the liquid T1/2, the reverse was true. Correlation between GM and ANT (r = 0.939) was better than between GM and LAO (r = 0.839); however, both LAO and ANT views correlated well with GM liquid emptying. It is concluded that the LAO view can replace GM gastric emptying methods in postpancreaticoduodenectomy patients for evaluation of both solid and liquid emptying, although the ANT view appears completely adequate for the study of liquid emptying.