Role of Paracoccidioides brasiliensis cell wall fraction containing beta-glucan in tumor necrosis factor-alpha production by human monocytes: correlation with fungicidal activity

The polysaccharide fraction of Paracoccidioides brasiliensis mycelial cell wall (F1 fraction), the active component of which is composed of beta-glucan, was investigated in regard to the activation of human monocytes for fungal killing. The cells were primed with interferon-gamma (IFN-gamma) or F1 (100 and 200 mug ml(-1)) or F1 (100 and 200 mug ml(-1)) plus IFN-gamma for 24 h and then evaluated for H2O2 release. In other experiments, the cells were pretreated with the same stimuli, challenged with a virulent strain of P. brasiliensis and evaluated for fungicidal activity and levels of tumor necrosis factor (TNF-alpha) in the supernatants. F1 increased the levels of H2O2 in a similar manner to IFN-gamma. However, a synergistic effect between these two activators was not detected. on the contrary, a significant fungicidal activity was only obtained after priming with IFN-gamma plus F1. This higher activity was associated with high levels of TNF-alpha in the supernatants of the cocultures. Overall, P. brasiliensis F1 fraction induced human monocytes to release relatively high levels of TNF-alpha, which, in combination with IFN-gamma, is responsible for the activation of human monocytes for effective killing of P. brasiliensis.

Solitary fibrous tumor with atypical histological features occurring in the palatine tonsil: an uncommon neoplasm in an uncommon site

Solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm that usually arises in the pleura. Although this tumor has been described in other sites, including the head and neck area, in the oropharynx it is extremely rare. We report the first case of a SFT arising from the palatine tonsil of a 62-year-old man. The tumor consisted of spindle-shaped cells distributed in a haphazard pattern and presented atypical histological features such as hypercellular areas and high mitotic count. Immunohistochemical studies showed strong positivity for CD34 and bcl-2, and weak positivity for desmin. Smooth muscle actin, S-100 protein and cytokeratines were negative. The patient was well without disease 1 year after surgery.

Testicular biopsy with Tru-Cut needle in conjunction with fibrin adhesive or nylon suture: assessment of post-biopsy testicular function in rams

Testicular biopsy has been a complementary technique for clinical and research purposes to evaluate reproductive function in males. However, hemorrhage, inflammation, degeneration, and adhesion are factors that might limit the use of this procedure. In order to minimize these potential problems, fibrin glue derived from snake venom, a tissue adhesive with sealing, hemostatic, and healing properties, was used in conjunction with bilateral testicular biopsy with the Tru-Cut needle and was compared with a more conventional technique that uses nylon suture. Thirty mature rams were randomly assigned to three groups of 10 animals each, as follows: nonsurgical control group (no scrotal surgery, or biopsy); biopsy + glue group (fibrin glue on puncture sites and skin incisions) and biopsy + suture group (compression with swab on puncture sites and suturing of skin incision). The surgeries of the rams in the biopsy groups were performed on the same day, which was designated Day 0 for all three groups. Data of scrotal circumference, number of spermatozoa per ejaculum, percentage of morphologically abnormal spermatozoa, spermatozoa motility, and serum testosterone concentrations from Days -7, 20, 40, 60, 80 and 100 were evaluated. There were no significant differences between groups within days for any of the parameters evaluated. In conclusion, the testicular biopsy procedure using the Tru-Cut needle in conjunction with conventional nylon suture or the more novel fibrin glue in rams did not affect any of the parameters of testicular function evaluated in this study and was shown to be relatively simple, safe and efficient. (C) 2002 Published by Elsevier B.V. B.V.

Tumor necrosis factor-alpha in gestation and puerperium of women with gestational hypertension and pre-eclampsia

Problem High plasma levels of tumor necrosis factor-alpha (TNF-alpha) in pregnant women have been associated with the pathogenesis of pre-eclampsia (PE). This study evaluated TNF-alpha plasma levels and monocyte production in gestational hypertension (GH) and PE during gestation and at puerperium.Method of study This study included 128 women, of whom 20 were non-pregnant (NP) normotensive (NT), and 108 were pregnant: 36 NT, 27 with GH, and 45 with PE. Peripheral blood plasma was used for TNF-alpha and uric acid determination. TNF-alpha was determined in plasma and lipopolysaccharide (LPS)-stimulated and non-stimulated monocyte supernatants by L929 bioassay.Results Tumor necrosis factor-alpha and uric acid plasma levels were higher in PE than in GH pregnancies. In both hypertensive groups, these parameters positively correlated and were significantly more elevated than in NT and NP women. TNF-alpha plasma levels and monocyte production were higher in hypertensive than in NT women during gestation, and significantly decreased at puerperium. Although decreased, TNF-alpha release in LPS-stimulated PE monocytes, was still significantly higher than in the other pregnant groups.Conclusion In vivo monocyte activation in GH and PE pregnant women was characterized by in vitro TNF-alpha production. The fact that higher circulating concentrations of TNF-alpha and uric acid were observed in PE than in GH suggests an association with disease severity.

Downregulation of the RECK-tumor and metastasis suppressor gene in glioma invasiveness

Invasive behavior is the pathological hallmark of malignant gliomas, being responsible for the failure of surgery, radiation, and chemotherapy. Matrix metalloproteinases (MMPs) are essential for proper ECM remodeling and invasion. The tumor and metastasis suppressor RECK protein regulates at least three members of the MMPs family: MMP-2, MMP-9, and MT1-MMP. In order to mimic the in vivo invasion process, A172 and T98G, respectively, non-invasive and invasive human glioblastoma cell lines, were cultured onto uncoated (control) or type I collagen gel-coated surface, and maintained for up to 7 days to allow establishment of the invasive process. We show that the collagen substrate causes decreased growth rates and morphological alterations correlated with the invasive phenotype. Electronic transmission microscopy of T98G cells revealed membrane invaginations resembling podosomes, which are typically found in cells in the process of crossing tissue boundaries, since they constitute sites of ECM degradation. Real time PCR revealed higher RECK mRNA expression in A172 cells, when compared to T98G cells and, also, in samples obtained from cultures where the invasive process was fully established. Interestingly, the collagen substrate increases RECK expression in A172 cells and the same tendency is displayed by T98G cells. MMPs-2 and -9 displayed higher levels of expression and activity in T98G cells, and their activities are also upregulated by collagen. Therefore, we suggest that: (1) RECK down regulation is critical for the invasiveness process displayed by T98G cells; (2) type 1 collagen could be employed to modulate RECK expression in glioblastoma cell lines. Since a positive correlation between RECK expression and patients survival has been noted in several types of tumors, our results may contribute to elucidate the complex mechanisms of malignant gliomas invasiveness.

Importance of cone beam computed tomography for diagnosis of calcifying cystic odontogenic tumor associated to odontoma. Report of a case

The calcifying cystic odontogenic tumour (CCOT) is a rare benign cystic neoplasm not infrequently associated with odontoma. This report documents a case of CCOT associated with compound odontoma arising in the anterior maxilla in a 25-year-old woman. Conventional radiographs showed a large calcified mass with poorly visualized radiolucent margins. The extent and condition of the internal structure of the CCOT associated with odontoma was able to be determined based on radiographic findings from cone beam computed tomography. This advanced image technique proved to be extremely useful in the radiographic assessment of this particular neoplasm of the jawbones.

CDKN2A promoter methylation is related to the tumor location and histological subtype and associated with Helicobacter pylori flaA(+) strains in gastric adenocarcinomas

Promoter hypermethylation of CDKN2A (p16INK4A protein) is the main mechanism of gene inactivation. However, its association with Helicobacter pylori infection is a controversial issue. Therefore, we examined a series of gastric adenocarcinomas to assess the association between p16INK4A inactivation and H. pylori genotype (vacA, cagA, cagE, virB11 and flaA) according to the location and histological subtype of the tumors. p16INK4A expression and CDKN2A promoter methylation were found in 77 gastric adenocarcinoma samples by immunohistochemistry and methylation-specific PCR, respectively. Helicobacter pylori infection and genotype were determined by PCR. A strong negative correlation between immunostaining and CDKN2A promoter region methylation was found. In diffuse subtype tumors, the inactivation of p16INK4A by promoter methylation was unique in noncardia tumors (p = 0.022). In addition, H. pylori-bearing flaA was associated with non-methylation tumors (p = 0.008) and H. pylori strain bearing cagA or vacAs1m1 genes but without flaA was associated with methylated tumors (p = 0.022 and 0.003, respectively). Inactivation of p16INK4A in intestinal and diffuse subtypes showed distinct carcinogenic pathways, depending on the tumor location. Moreover, the process of methylation of the CDKN2A promoter seems to depend on the H. pylori genotype. The present data suggest that there is a differential influence and relevance of H. pylori genotype in gastric cancer development.

Gingival metastasis from salivary duct carcinoma of the parotid gland

Background: This article reports a rare case of metastasis of salivary duct carcinoma of the parotid gland to the gingiva and reviews the occurrence of metastatic processes to the oral mucosa.Methods: A 67-year-old white male presented with a chief complaint of a painless nodular tissue growth on the gingiva with reportedly 5 months of evolution. The intraoral examination revealed a reddish, superflcially ulcerated nodular lesion (similar to 2 cm in diameter) on the right mandibular buccal attached gingiva, and the clinical aspect was that of a benign reactive lesion. The patient had undergone a parotidectomy for removal of a salivary duct carcinoma of the parotid gland almost 1 year before. A biopsy of the gingival lesion was performed, and the biopsied tissue was forwarded for histopathologic examination.Results: The analysis of the histopathologic sections of the gingival lesion revealed histomorphologic characteristics very similar to those of the primary parotid gland tumor. The definitive diagnosis was gingival metastasis from a salivary duct carcinoma of the parotid gland. The patient died of complications of a pulmonary metastasis I month after the diagnosis of the oral metastatic lesion.Conclusions: Gingival lesions that mimic reactive and hyperplastic lesions may be metastases from malignant neoplasias of diverse origins. An accurate and timely diagnosis is crucial to establish proper and immediate treatment of the metastatic tumor and possibly identify an occult primary malignant neoplasia.

Inactivation of COX-2, HMLH1 and CDKN2A Gene by Promoter Methylation in Gastric Cancer: Relationship with Histological Subtype, Tumor Location and Helicobacter pylori Genotype

Objective: We aimed to evaluate the inactivation of COX-2, HMLH1 and CDKN2A by promoter methylation and its relationship with the infection by different Helicobacter pylori strains in gastric cancer. Methods: DNA extracted from 76 H. pylori-positive gastric tumor samples was available for promoter methylation identification by methylation-specific PCR and H. pylori subtyping by PCR. Immunohistochemistry was used to determine COX-2, p16(INK4A) and HMLH1 expression. Results: A strong negative correlation was found between the expression of these markers and the presence of promoter methylation in their genes. Among cardia tumors, negativity of p16(INK4A) was a significant finding. on the other hand, in noncardia tumors, the histological subtypes had different gene expression patterns. In the intestinal subtype, a significant finding was HMLH1 inactivation by methylation, while in the diffuse subtype, CDKN2A inactivation by methylation was the significant finding. Tumors with methylated COX-2 and HMLH1 genes were associated with H. pylori vac A s1 (p = 0.025 and 0.047, respectively), and the nonmethylated tumors were associated with the presence of the gene flaA. Conclusions: These data suggest that the inactivation of these genes by methylation occurs by distinct pathways according to the histological subtype and tumor location and depends on the H. pylori genotype. Copyright (C) 2011 S. Karger AG, Basel