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Biomedical subjects

A Karameris

Publications and source records attributed to A Karameris.

At least 19 recordsLinked to original sources

Evaluation of epidermal growth factor receptor gene and chromosome 7 alterations in squamous cell carcinoma of the larynx, using chromogenic in situ hybridization on tissue microarrays.

AIMS: To identify subgroups of patients with squamous cell carcinoma (SCC) of the larynx, characterized by the specific deregulation mechanism of the epidermal growth factor receptor (EGFR) gene, and to evaluate EGFR protein expression levels and correlate these with biological and clinicopathological parameters. MATERIALS AND METHODS: Using tissue microarray technology, 50 formalin-fixed, paraffin-embedded primary laryngeal SCCs were cored and re-embedded into one block. Immunohistochemistry and chromogenic in situ hybridization were performed. RESULTS: Epidermal growth factor receptor protein over-expression was observed in 27/50 (54 per cent) cases and was statistically associated with tumour grade (p=0.028). Epidermal growth factor receptor gene alterations were identified in 5/50 (10 per cent) cases, which demonstrated amplification (n=4) and deletion (n=1). Chromosome 7 instability was detected in 8/50 (16 per cent) cases. CONCLUSIONS: Epidermal growth factor receptor over-expression is a frequent event in SCCs, but it does not predict a specific molecular mechanism of gene deregulation for targeted therapeutic strategies via monoclonal antibodies.

Carcinoma, Squamous Cell↗

Cellular immunophenotyping of exfoliative dermatitis in canine leishmaniosis (Leishmania infantum).

Lymphocyte subsets, major histocompatibility complex (MHC)-II expressing cells and number of amastigotes in the epidermis and dermis were investigated immunohistochemically in 48 dogs with patent leishmaniosis, with or without exfoliative dermatitis (ED) to study the immunopathogenesis of this common cutaneous form of the disease. Skin biopsies were obtained and compared for ED sites (group A, n = 26), normal-appearing skin from the same animals (group B, n = 24), and leishmanial dogs not exhibiting ED (group C, n = 22), and normal controls (group D, n = 22). The CD3+, CD45RA+, CD4+, CD8+ (CD8a+), CD21+, and MHC-II+ cells and leishmania amastigotes were identified immunohistochemically and counted with the aid of an image analysis system. Pyogranulomatous to granulomatous dermatitis, expressed in various histopathological patterns, was noticed in all groups A and B and in half of group C dogs. In the epidermis, the low number of T-cells and their subsets did not differ significantly between groups A and B, but CD8+ outnumbered CD4+ lymphocytes in both groups. MHC-II+ expression on epidermal keratinocytes was intense in the skin with and without lesions from dogs with ED but not in group C dogs. CD3+, CD8+ and MHC-II+ cells were fewer in group C compared to group A and B dogs. In the dermis, CD3+ cells in group A animals were mainly represented by the CD8+. CD45RA+ and CD21+ cells were also seen in high numbers. MHC-II expression, potentially in lymphocytes, fibroblasts, dendritic cells, and macrophages was intense. The numbers of all cellular subpopulations in the dermis were significantly different between the groups, being highest in group A and lowest in group D. In sebaceous adenitis sites, CD4+ outnumbered CD8+ cells in contrast to the neighbouring dermis and the epidermis. The number of CD21+ and CD45RA+ cells was much lower in the inflamed sebaceous glands compared to the dermis. Finally, the number of amastigotes in the normal-appearing skin was significantly higher in the ED dogs (group B) than in those not exhibiting this cutaneous form of the disease (group C).

Animals↗

Elevated serum levels of the apoptosis related molecules TNF-alpha, Fas/Apo-1 and Bcl-2 in oral lichen planus.

BACKGROUND: The serum circulatory levels of apoptosis related molecules measured in patients with oral lichen planus (OLP) and healthy individuals in order to investigate possible alterations associated with the clinical forms of OLP. METHODS: Serum levels of tumor necrosis factor (TNF)-alpha, soluble Fas (sFas) and Bcl-2 studied by enzyme-linked immunosorbent assay in whole blood samples in 13 OLP reticular, 13 OLP atrophic-erosive form patients and 26 healthy subjects. RESULTS: Significantly elevated levels of TNF-alpha and sFas detected in OLP patients as compared with controls. Serum concentrations of Bcl-2 although increased in 17/26 patients, they were not statistically significant. Reticular OLP exhibited slightly elevated TNF-alpha and significantly elevated Bcl-2 serum levels, compared with erosive OLP. CONCLUSIONS: These data suggest that a putative dysfunction in the Fas/FasL mediated apoptosis might be involved in the OLP pathogenesis. A downregulation of Bcl-2 serum levels in the atrophic-erosive OLP may be associated with promotion of the disease activity.

Apoptosis↗

The association between CagA status and the development of esophagitis after the eradication of Helicobacter pylori.

BACKGROUND: Strains of Helicobacter pylori with the cytotoxine-associated gene A (cagA) are linked to severe forms of gastroduodenal disease. Although eradication of H. pylori may predispose to the development of reflux esophagitis, the effects of CagA status on risk of esophagitis after successful H. pylori treatment are not known. METHODS: We studied 50 consecutive patients without esophagitis in whom H. pylori was eradicated successfully. CagA status was determined by immunoblotting sera from patients against H. pylori antigens. Patients underwent upper gastrointestinal endoscopy before eradication and 6, 12, 18, and 24 months after eradication or when reflux symptoms occurred. Biopsy specimens of the antrum and corpus were evaluated for gastritis before H. pylori eradication and at the end of the study. The sum of the scores for acute and chronic inflammation (both measured on a 0 [absent] to 3 [severe] scale) comprised the total gastritis severity score. RESULTS: In a multivariate proportional hazards regression analysis, positive CagA serology (hazard ratio [HR] = 10, 95% confidence interval [CI]: 1.3 to 81) and moderate-to-severe corpus gastritis (total severity score > or =4) before eradication (HR = 2.3, 95% CI: 1.2 to 6.1) were independent risk factors for the development of esophagitis after H. pylori eradication. CONCLUSION: Patients infected with strains of H. pylori that are cagA-positive are at increased risk of developing esophagitis after eradication of H. pylori.

Adult↗

Overexpression of matrix-metalloproteinase-9 in human breast cancer: a potential favourable indicator in node-negative patients.

Matrix metalloprotease-9 (MMP-9; 92 kDa type IV collaganase, gelatinase B) is regarded as, important for degradation of the basement membrane and extracellular matrix during cancer invasion and other tissue-remodelling events. In this study we evaluate the prognostic value of MMP-9, by immunoperoxidase staining in a series of 210 breast cancer tissues. The results were quantitated using the HSCORE system, which consider both staining intensity and the percentage of cells stained at given intensities. MMP-9 status was compared with the concentration of cytosolic Cathepsin-D and with other established prognostic factors, in terms of disease free survival and overall survival. The median follow-up period was 62 months. MMP-9 staining was observed primarily in cancer cells, and to a lesser degree in surrounding stromal cells. MMP-9 expression was not detected in normal breast tissue. Levels of MMP-9 expression below the cut-off point were more frequently observed in larger (P = 0.014), invasive ductal histologic (P = 0.037), progesterone receptor (PR)-negative and PR-strong positive tumours (P< 0.001), as well as samples belonging to patients with stage III-IV disease (P = 0.009) and age 45-55 years (P = 0.011). In univariate analysis, node-negative breast cancer patients with tumors positive for MMP-9 had a considerable reduction in risk for relapse (RR = 0.45;P = 0.039) or death (RR = 0.32;P = 0.009). Multivariate analysis indicated that MMP-9 status was an independent favourable predictor of OS (RR = 0.47;P = 0.034) in node-negative but not in node-positive patients. Our results suggest that MMP-9 may be an independent favourable prognostic factor in node-negative breast cancer patients. The overexpression of MMP-9 in breast cancer may be also used as a marker to subdivide node negative breast cancer patients in order to determine the optimal treatment modality.

Adult↗

Effectiveness of acid suppression in preventing gastroesophageal reflux disease (GERD) after successful treatment of Helicobacter pylori infection.

There is evidence that Helicobacter pylori eradication might predispose to gastroesophageal reflux disease (GERD). The aim of this prospective study was to examine the effectiveness of antisecretory treatment, after successful H. pylori eradication, in preventing GERD, since no data exist so far. Eighty initially H. pylori(+) patients, without GERD at the time of H. pylori eradication [50 peptic ulcer (PU) and 30 nonulcer (NU), 55 men, 25 women, median age 38 years, range 19-57], after successful H. pylori eradication were randomized to recieve either omeprazole 20 mg daily (group A) or no treatment (group B) for one year. All patients underwent upper gastrointestinal endoscopy at 0, 6, and 12 months or when GERD symptoms occurred. There were 40 patients in each group, and there were no statistically significant differences between the two groups in terms of sex, age, body weight, ulcer/no ulcer ratio, and other demographic data. Seven patients from group A and five patients from group B were lost to follow-up, and therefore there were 33 and 35 patients in groups A and B, respectively, who completed the study. One of 33 patients in group A (3%) and 10/35 (28.5%) in group B developed GERD symptoms during follow-up (P = 0.0022). The respective values for esophagitis were 0/33 (0%) and 6/35 (17.1%) (P = 0.0083). In conclusion, antisecretory treatment in H. pylori(+) patients, after successful eradication, is effective in preventing GERD.

Adult↗

TNF-alpha expression and apoptosis-regulating proteins in oral lichen planus: a comparative immunohistochemical evaluation.

Apoptosis appears to be the mode of cell death by which damaged cells are removed from the lesional tissue in oral lichen planus (OLP). In the present study, OLP biopsies were immunohistochemically evaluated for TNF-alpha and apoptosis-regulating proteins in an attempt to compare their phenotypic expression. Deparaffinized tissue sections from 22 OLP and 10 control oral biopsy specimens were immunohistochemically stained with anti-Bcl-2, anti-Bcl-x, anti-Bax and anti-TNF-alpha antibodies. Keratinocytes did not show any immunoreactivity for Bcl-2, while a uniform intense staining for this protein was evident in the lymphocytic infiltrate of OLP specimens. Immunoreactivity for TNF-alpha was seen in 17/22 OLP cases. All control tissues were TNF-alpha negative, thus indicating a possible involvement of this cytokine in the pathogenesis of OLP The differences in the staining intensities of Bcl-x and Bax between OLP and normal epithelium were slight; therefore an obvious association of the phenotypic TNF-alpha expression with these apoptosis-regulating proteins was not apparent.

Adult↗

c-mos immunoreactivity is an indicator of good prognosis in lung cancer.

AIMS: Reports concerning the expression of cytoplasmic components of the mitogen-activating protein kinase (MAPK) pathway in lung cancer are limited. One of the molecules participating in this pathway is the product of the c-mos proto-oncogene. In vitro investigations, in somatic cells, have shown that c-mos expression has opposing effects on cell cycle progression suggesting that it may represent an important determinant of aberrant cell function. In this study we analysed, by immunohistochemical means, its status in a series of lung carcinomas and correlated the findings with clinicopathological parameters and survival of the patients. METHODS AND RESULTS: Sixty cases of lung carcinomas were included in the study. These comprised 52 non-small (NSCLCs) and eight small cell lung carcinomas (SCLCs). Sections from the carcinomas were immunostained with the polyclonal anti-c-mos antibody P-19. Specificity was tested by using the appropriate control peptide and control cell lines. Expression was observed in 63% of the cases, with NSCLCs showing higher reactivity (67%) than SCLCs (37.5%). Staining was observed mainly to the cytoplasm and membranes of the cancerous cells, but some nuclei reacted as well. An intratumour heterogeneous immunoreactivity was noticed. The most interesting and unexpected finding was that c-mos positive staining was associated with better recurrence-free survival in our series, regardless of histological type (P = 0.035). Furthermore, favourable disease-related and recurrence-free survival was observed in the SqC group with c-mos immunoreactivity (P < 0. 001). CONCLUSIONS: c-mos proto-oncogene is expressed in a significant proportion of lung carcinomas and may play a role in its development. The fact that its expression is associated with a relatively good prognosis may be indicative of a negative impact on tumour growth.

Aged↗

Eosinophilic granuloma of the lung presenting as an endobronchial mass.

A 19-yr-old male presented with left lung parahilar consolidation and clinical signs of pneumonia. These symptoms were secondary to an endobronchial mass in the apical segment of the lower lobe. At thoracotomy an apical segment bronchial sleeve resection successfully extirpated what later proved to be an endobronchial eosinophilic granuloma. To the authors' knowledge this is the first case report of an endobronchial eosinophilic granuloma in an adult.

Adult↗

Endogenous interleukin 6 conveys resistance to cis-diamminedichloroplatinum-mediated apoptosis of the K562 human leukemic cell line.

Cisplatin is an effective chemotherapeutic agent that elicits its antineoplastic activity by binding to DNA and disrupting template functions. IL-6 is a cytokine which has been shown to play a central role in host immunological defense mechanisms. Although K562 leukemic cells have been shown to secrete IL-6, little is known of whether there exists a correlation between the expression of IL-6 and the resistance of these cells to anticancer chemotherapeutic agents. To determine the contribution of IL-6 to the regulation of cisplatin-induced apoptosis in K562 cells, we examined whether treatment of K562 cells and cisplatin-resistant K562 subclones with anti-IL-6 mAb enhances their sensitivity to cisplatin. The results show that cis-diamminedichloroplatinum (CDDP) resistance was overcome by treatment with nontoxic doses of CDDP in combination with anti-IL-6 mAb. When we tested if the synergistic effect of anti-IL-6 and cisplatin could restore the ability of K562 mutant cells to undergo apoptosis, we found the typical DNA laddering in these cells, even in the presence of a nontoxic dose of the drug. Treatment of cells with anti-IL-6 reduced the levels of glutathione. The current studies show that anti-IL-6 mAb sensitized CDDP-resistant K562 cells to CDDP by induction of apoptotic death and the reduction of glutathione levels might be implicated in the enhanced cytotoxicity observed.

Antibodies, Monoclonal↗

Serologic detection of CagA positive Helicobacter pylori strains predicts the presence of peptic ulcer in young dyspeptic patients.

BACKGROUND: Helicobacter Pylori infection has been strongly associated with upper gastrointestinal (GI) disease, especially duodenal ulcer. Endoscopy or contrast radiography is needed to diagnose and appropriately manage peptic ulcer disease. These diagnostic procedures, however, are time consuming and expensive; endoscopy is invasive and contrast radiography cannot help in the diagnosis of H pylori infection. Our aim was to examine in a prospective study the relation between serologic detection of cytotoxic associated gene (CagA) H pylori strains and endoscopic findings among young dyspeptic patients to determine whether this noninvasive test can help differentiate patients with from those without ulcers. METHODS: One hundred patients younger than 45 years with dyspepsia referred for upper GI endoscopy were included in the study. During endoscopy antral biopsy specimens were obtained for the rapid urease test and histologic examination. At histologic examination gastritis was graded from 0 (normal histologic features) to 3 (severe gastritis). After endoscopy blood was obtained for serologic determination of CagA status. RESULTS: Among the 100 patients 56 were H pylori positive and 44 were H pylori negative. In the group of 56 H pylori-positive patients 36 (64.3%) had peptic ulcers and 20 (35.7%) did not. Among patients with peptic ulcer 34 of 36 (94.4%) were CagA positive and 2 (5.6%) were CagA negative. The respective values for the group of patients without ulcers were 9 of 20 (45%) and 11 of 20 (55%). The difference in the proportion of CagA-positive subjects between the group with and that without peptic ulcer was highly significant (p < 0.0001). CONCLUSIONS: Among young patients with dyspepsia, CagA seropositivity is highly associated with duodenal ulcer at endoscopy.

Adolescent↗

Tumors of the ribs: experience with 47 cases.

OBJECTIVES: To emphasise the existing difficulties in differentiating benign from malignant rib tumours, and especially the problems that a clinical doctor encounters when dealing with a hyperplastic rib. METHODS: Forty-seven patients with rib tumour underwent surgery in a period of 12 years (1984-1996). In 40 cases (85%), the lesion was benign and in seven (15%) was malignant. Twenty-one benign tumours originated from cartilage and bone, seven were inflammatory, six originated from the bone marrow, and minor percentages (2.5-5%) had vascular, neurogenous, degenerative or miscellaneous origin. Three of the malignant tumours were primary chondrosarcomas and two were metastatic from kidney. The rest were metastatic from stomach (adeno-Ca), and skin (melanoma). The mean age in the benign group was 25.2 years and in the primary malignant group was 20.7 years. Related symptoms were pain (47%) and swelling (42.5%). One-third (32%) of the patients were asymptomatic and the lesion was accidentally found during routine chest radiography. All patients were treated surgically with wide excision of the tumour and the diagnosis was established histologically. RESULTS: Resection was complete and curative in all cases without recurrence. CONCLUSIONS: Since the likelihood of malignancy cannot be excluded, all rib tumours should be considered malignant until proven otherwise. Therefore, prompt intervention is necessary and wide and radical initial excision of the involved rib is advocated.

Adolescent↗

Predictive factors and prevalence of follicular gastritis in adults with peptic ulcer and nonulcer dyspepsia.

Follicular gastritis is an important histological entity, because it may progress to overt gastric MALT lymphoma. However, there is no universal agreement on whether there is any correlation of follicular gastritis with histological features of the antral mucosa or on the prevalence of follicular gastritis. To shed further light on these issues, we studied antral biopsies obtained from 735 adult patients, who had participated in six consecutive clinical trials. They included 348 patients with duodenal ulcer, 82 with gastric ulcer, and 305 with nonulcer dyspepsia. The Sydney classification system of gastritis was used, using a score of 0-3 to grade degree and activity of inflammation, gland atrophy, intestinal metaplasia, and H. pylori colonization density. Follicular gastritis was defined as prominent lymphoid follicles with no lymphoepithelial lesion. None of the H. pylori-negative patients (N = 159) had follicular gastritis. Among H. pylori-positive patients, 80/340 (23.5%) with duodenal ulcer, 5/77 (6.5%) with gastric ulcer, and 20/159 (12.6%) with nonulcer dyspepsia had follicular gastritis (P < 0.001). Multivariate discriminant analysis selected the following four significant predictor variables for follicular gastritis (Wilks lambda = 0.91, chi2 = 70.6, df = 4, P < 0.001): gastritis sum score, atrophic gastritis, age of the patient, and disease. The prevalence of follicular gastritis was linearly correlated (gamma = 24.55 - 0.98chi, r = -0.62, F1,11 = 6.12, P = 0.03) with the age groups of the 576 H. pylori-positive patients studied. In conclusion, follicular gastritis is highly correlated with H. pylori-caused severe, active gastritis. It is mostly prevalent in the young H. pylori-infected patients with duodenal ulcer.

Adolescent↗

Relationship of Helicobacter pylori CagA status to gastric cell proliferation and apoptosis.

Despite the fact that the association of Helicobacter pylori with an increased risk of gastric cancer is well documented, the exact mechanisms of this association have not been elucidated. Our aim was to shed some light on these mechanisms by studying the relationship of H. pylori CagA status to gastric cell proliferation and apoptosis, since both play an important role in gastrointestinal epithelial cell turnover and carcinogenesis. We studied fifty patients [32 men, 18 women, median age 39.5 years (range 18-67)], referred for upper gastrointestinal endoscopy, from whom antral biopsies were taken. On biopsy specimens gastritis was estimated by scoring the severity of inflammatory infiltrate, and the presence of atrophy and intestinal metaplasia were also noted. The gastric cell proliferation index (PI) was estimated by AgNOR staining, the epithelial apoptotic index (AI) was measured by special staining for apoptosis, and CagA status was determined serologically by immunoblotting the sera of patients against H. pylori antigens. Thirty-eight (76%) of the 50 patients were H. pylori (positive) and 12 (24%) H. pylori (negative). Among the 38 H. pylori(+) patients, 28 (73.6%) were CagA(+) and 10 (24.6%) CagA(-). In the H. pylori CagA(+) and CagA(-) groups, the PI values [median (ranges)] were 5 (4-7) and 3.7 (3.5-5.5), respectively (P < 0.05). In addition the difference in PI between the H. pylori CagA(+) and H. pylori(-) groups was highly significant (P < 0.001). Concerning apoptosis, in the H. pylori CagA(+) and CagA(-) groups, the values for AI were 1 (1-30) and 5.5 (1-35), respectively (P < 0.05). In addition, the difference in AI between the H. pylori CagA(-) and H. pylori(-) groups, was significant (P < 0.05). We conclude that H. pylori CagA(+) strains induce increased gastric cell proliferation, which is not accompanied by a parallel increase in apoptosis. This might explain the increased risk for gastric carcinoma that is associated with infection by H. pylori CagA(+) strains.

Adult↗