Biomedical subjects

N Gale

Publications and source records attributed to N Gale.

At least 19 recordsLinked to original sources

PubMed2006

Distribution of Epstein-Barr virus genotypes in throat washings, sera, peripheral blood lymphocytes and in EBV positive tumor biopsies from Slovenian patients with nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignancy closely associated with Epstein-Barr virus (EBV). It is prevalent among the Chinese of Southern China, whereas outside China, the position seems to be different. The aim of this study was to determine the distribution of EBV genotypes in the patients with NPC in Slovenia, which is a nonendemic area. Detection of EBV was undertaken by testing the throat washes, sera, peripheral blood lymphocytes (PBLs), and biopsies of primary tumors of 48 patients with NPC in Slovenia. The sera of 20 patients with serologically confirmed primary EBV infection served as a control clinical material. The analysis of genotypes was carried out on three regions of EBV genome; BamHI WYH, BamHI I, and BamHI F, using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The results show that, in Slovenia, the predominant combination of EBV genotypes based on the differences in the three genomic regions is ADF. This combination was found in 56 out of 103 different EBV positive clinical samples (throat washes, sera, PBLs, and tumor biopsies) of patients with NPC and in 15 out of 17 sera of patients with primary EBV infection. Very low number of genotypes C and f were detected, in spite of the fact that these two genotypes were considered to be associated with the development and/or maintenance of NPC in Southern China. Genotype f was found in only two tumor biopsies; in all other clinical samples (throat washes, sera and PBLs), genotype F was detected. Genotype C was proven in 31/103 clinical samples, with the highest percentage in tumor biopsies (37.5%). As in the NPC patients from other countries (Alaska is an exception), genotype A was predominant and was detected in 86/103 clinical samples. Genotype B was found in 15 clinical samples of patients with NPC and in 3 the two genotypes A and B were found. In comparison to China, these results show different EBV genotypes distribution. It seems that the genetic disposition of human population is an important factor that may contribute to different susceptibility for specific EBV genotypes.

Adolescent↗

PubMed2006

Pseudovascular adenoid squamous-cell carcinoma of the oral cavity--a report of two cases.

Informed consent was obtained for the publication of the patients' details in this report. Two cases of pseudovascular adenoid squamous-cell carcinoma (SCC) in the oral cavity are described, which were characterised by acantholysis of the tumour cells, with formation of anastomosing spaces and channels mimicking an angiosarcoma. Both tumours contained foci of SCC suggesting the correct diagnosis: in one patient conventional SCC, and in the other, a spindle-cell carcinoma. The pathogenesis of pseudovascular adenoid SCC is unknown. Our cases were characterised by loss of immunohistochemical expression of E-cadherin, one of the major adhesion molecules of epithelial cells. Pseudovascular adenoid SCC is suggested to be pathogenetically related to the loss of E-cadherin expression, leading to the loss of tumour cell-cell adhesion.

Aged↗

PubMed2005

Cytological features of lipoblastoma: a report of three cases.

Lipoblastoma is a rare benign neoplasm occurring mostly in children under the age of three. Accurate preoperative diagnosis is mandatory for planning the treatment. The main aim of this study is to establish the cytological features of lipoblastoma and to answer the question: "Is cytological diagnosis of lipoblastoma reliable?"Preoperative fine-needle aspiration biopsy (FNAB) and tissue sections of three children treated for lipoblastoma at the Division of Pediatrics, University Medical Center, Ljubljana, Slovenia, in the period from 1997 to 2004 were reexamined. The Giemsa- and Papanicolaou-stained FNAB smears were moderately or poorly cellular and contained lipocytes, lipoblasts, and spindle cells in various proportions. The tumor cells were in clusters and tissue fragments or as single cells. Thin branching capillaries were observed in most of the clusters and tissue fragments. In the background, abundant myxoid extracellular material and naked oval nuclei were present. In the first case, the cytological diagnosis was benign soft-tissue tumor, in the second the diagnosis was not conclusive and the last case was correctly diagnosed as lipoblastoma. In the differential diagnosis of the second case, both lipoblastoma and liposarcoma were considered cytologically as well as histologically. At 7-yr follow-up, there is no evidence of the disease.Thus, we conclude that lipoblastoma with typical cytological features could be accurately diagnosed by FNAB. However, tumors containing numerous lipoblasts could pose a diagnostic problem.

Biopsy, Fine-Needle↗

PubMed2005

VEGF trap as a novel antiangiogenic treatment currently in clinical trials for cancer and eye diseases, and VelociGene- based discovery of the next generation of angiogenesis targets.

The concept that tumors can be controlled by directly targeting their vascular supply has finally come of age, because clinical trials using a humanized monoclonal antibody that blocks VEGF have demonstrated exciting efficacy in cancer patients, as well as in vascular eye diseases that can lead to blindness. However, data suggest that these current regimens may not provide complete VEGF inhibition and, thus, that the maximum therapeutic potential of VEGF blockade has not yet been achieved. We describe the status of a very potent and high-affinity VEGF blocker, termed the VEGF Trap, that may provide the opportunity to maximize the potential of VEGF blockade in cancer as well as in vascular eye diseases. We also describe use of the VEGF Trap as a research tool, when coupled to high-throughput mouse genetics approaches such as VelociGene that can be exploited in strategies to discover and validate the next generation of angiogenesis targets.

Angiogenesis Inhibitors↗

PubMed2004

Human telomerase catalytic subunit gene re-expression is an early event in oral carcinogenesis.

AIMS: Detection of telomerase catalytic subunit (hTERT) mRNA has been used as a surrogate marker for estimation of telomerase activity. The exact role and timing of telomerase re-activation, a key enzyme implicated in cellular immortalization and transformation, in the multistep process of oral carcinogenesis is still unknown. The aim was to test the hypothesis that (i) quantitative rather than qualitative differences exist in the level of hTERT mRNA expression between normal oral mucosa, different grades of oral epithelial abnormalities and squamous cell carcinomas of the oral cavity, and that (ii) hTERT gene re-expression is an important, probably early event in oral carcinogenesis. METHODS AND RESULTS: The relative quantity of hTERT mRNA was analysed in 45 frozen oral epithelia representing different morphological stages of oral carcinogenesis classified according to the Ljubljana classification and in 37 oral squamous cell carcinomas, using a commercially available LightCycler Telo TAGGG hTERT Quantification kit. hTERT mRNA was not detected in normal or reactive hyperplastic oral epithelia, but was present in 43% of atypical hyperplasias (premalignant lesions), 60% of intraepithelial carcinomas and 68% of oral squamous cell carcinomas. Statistical analysis revealed two groups of oral epithelial changes, with significant differences in the levels of hTERT mRNA expression: 1, normal and reactive hyperplastic oral epithelium, and 2, atypical hyperplasia, intraepithelial carcinomas and squamous cell carcinomas. CONCLUSION: These data suggest that hTERT gene re-expression represents an early event in the multistep process of oral carcinogenesis, already detectable at the stage of precancerous oral epithelial changes. Nevertheless, other genetic aberrations appear to be necessary for progression of oral epithelial abnormalities towards invasive squamous cell carcinoma.

Carcinoma, Squamous Cell↗

PubMed2004

Survivin expression is a negative prognostic marker in laryngeal squamous cell carcinoma and is associated with p53 accumulation.

AIMS: To investigate survivin expression in laryngeal squamous cell carcinoma (LSCC), its prognostic significance and relation to p53 status. Survivin is an inhibitor of apoptosis protein that is overexpressed in cancer. It has been implicated in both prevention of apoptosis and cell cycle regulation. It has been suggested that wild-type p53 represses survivin expression. METHODS AND RESULTS: Expression of survivin and p53 was analysed in 68 archival biopsy specimens of LSCC by immunohistochemistry. Survivin was detected in 67 of 68 LSCC cases; the proportion of survivin-positive cells varied from 8.2% to 100%. It was localized in the nucleus and/or cytoplasm of tumour cells. Of LSCC cases, 31.8% were p53+. The number of survivin-positive cells was significantly higher in the p53+ group. A high level of survivin expression and a supraglottic site of the tumour were two independent adverse prognostic factors in LSCC. CONCLUSIONS: Survivin is expressed in a varying proportion of cells in virtually all cases of LSCC. A high level of its expression predicts poor survival. Loss of wild-type p53 is a possible mechanism of survivin up-regulation in LSCC.

Antigens, Neoplasm↗

PubMed2003

Inflammatory myofibroblastic tumour of paranasal sinuses with fatal outcome: reactive lesion or tumour?

Inflammatory myofibroblastic tumours (IMTs) are clinicopathologically distinctive but biologically controversial entities, which have been described in the lungs, abdomen, retroperitoneum, and extremities, but rarely affect the head and neck region. IMT usually follows a benign clinical course after radical excision, but invasive, locally recurrent, and metastatic forms of abdominal and mediastinal IMT have also been described. This report describes a case of IMT of the paranasal sinuses with a fatal outcome. A 22 year old woman was admitted to hospital as a result of epistaxis. Computed tomography scan and magnetic resonance imaging showed an expansive process in the paranasal sinuses, extending into the nasal cavity, orbita, and endocranium. The tumour progressed despite several surgical procedures. Radiotherapy, corticosteroids, and chemotherapy were unsuccessful, and the patient died four years after diagnosis, as a result of extensive intracranial spread of the tumour. This is the first known case of an IMT of the head and neck region with a fatal outcome. It shows that the aggressive behaviour of IMTs is not limited to abdominal and mediastinal locations, and supports recent observations that at least a subset of IMTs represents true neoplasia rather than reactive myofibroblastic proliferation.

Adult↗

PubMed2003

Human papillomavirus DNA in oral squamous cell carcinomas and normal oral mucosa.

To elucidate the putative etiologic role of human papillomaviruses (HPV) in oral carcinogenesis, a comparative study was carried out on 62 tissue specimens of oral squamous cell carcinoma (OSCC) and on 62 specimens of histologically normal oral mucosa obtained from the individuals who matched the subjects with OSCC in age, gender, localization of obtained tissue specimens, drinking and smoking habits. Internal control amplification showed that amplifiable DNA was recovered from 59/62 and 61/62 tissue samples of OSCC and normal oral mucosa, respectively. The amplification with two different HPV L1 and one HPV E6 consensus primer sets showed the presence of the HPV DNA genotypes 16, 33, 58 in 5/59 (8.4%) OSCC specimens and HPV genotypes 11, 16, 31, 68 in 4/61 (6.6%) tissue samples of normal oral mucosa tested. In the study in which a comparative examination of the presence of HPV DNA was for the first time performed on the tissue samples of the patients with OSCC and the age- and gender-matched control subjects there was no significant difference in the prevalence of HPV DNA among both study groups. Our results suggest that occasional findings of HPV DNA in OSCC tissue specimens may be the result of an incidental HPV colonization of oral mucosa, rather than of viral infection, and that HPVs play a limited role in the etiopathogenesis of the majority of OSCC.

Adult↗

PubMed2002

[The Ljubljana classification of epithelial hyperplastic laryngeal lesions: a morphometric evaluation of nuclear pleomorphism].

Epithelial hyperplastic laryngeal lesions (EHLL) are associated, with a varying degree of "epithelial risk"- to develop invasive carcinoma. Several classifications have been proposed but none has received a total agreement. The 1999 Ljubljana classification distinguished four grades: simple, abnormal and atypical hyperplasia and in situ carcinoma (ISC). The first two grades are considered benign lesions; the ISC is the malignant lesion, while the atypical hyperplasia is considered a "risky lesion". This is characterized by alterations of epithelial cells towards malignancy, but not to the extent to be found in carcinoma cells. Such characteristics refer to cytomorphological (e.g., nuclear hyperchromatism, nucleoli, increased nuclear/cytoplasmic ratio) and architectural (e.g. stratification, orientation, maturation) features. In the Ljubljana scheme, nuclear pleomorphism is one of the most important features. We wanted to improve the importance of nuclear pleomorphism in the basal cells layer in different classes of EHLL using morphometrical analysis. We studied 8 cases of simple hyperplasia, 10 of abnormal hyperplasia, 10 of atypical hyperplasia and 8 of ISC using the software SAM (Shape Analytical Morphometry). The results were submitted to univariate statistical analysis. Nuclear dimensions (maximum diameter, perimeter and area) showed a progressive increase from simple to atypical hyperplasias to ISC, while abnormal hyperplasia showed the lowest values. On the contrary, analytical parameters related to nuclear contour irregularities and asymmetries showed their highest values in abnormal hyperplasia nuclei. There were no significant differences between atypical hyperplasia and ISC, while it was possible to differentiate abnormal hyperplasia from the others. In conclusion basal nuclei of atypical hyperplasia and ISC are similar so that other cytological and morphological architectural parameters are necessary to distinguish the two lesions. Abnormal hyperplasia seems to be the biological category of 'proliferative " benign laryngeal epithelium; simple hyperplasia refers to "stable" - irritative epithelium.

Biopsy↗

PubMed2000

Wegener's granulomatosis in the upper respiratory tract.

Wegener's granulomatosis is a distinct clinico-pathological entity characterised by necrotising vasculitis of small arteries and veins in conjunction with the formation of granuloma in the upper and lower respiratory tracts, and glomerulonephritis. The vast majority of patients have antineutrophil cytoplasmic antibodies in the serum with a characteristic cytoplasmic pattern. However, in early phases of the disease only the upper respiratory tract may be affected, clinical and histological features may be nonspecific, and antineutrophil cytoplasmic antibodies not present. In this paper we present four patients with involvement of the upper respiratory tract suspicious for early Wegener's granulomatosis. We emphasise the significance of clinical, histological and serological parameters in the early detection of Wegener's granulomatosis.

Aged↗

PubMed2000

Eph receptors and ephrin expression in cranial motor neurons and the branchial arches of the chick embryo.

Cranial motor axons navigate along a variety of pathways to their targets in the periphery of the head. Whereas somatic motor axons innervate tongue and eye muscles, visceral motor axons innervate parasympathetic ganglia, and branchiomotor axons innervate the branchial arches. The formation of these diverse pathways must depend upon molecules present in the environment traversed by growing axons. We have analyzed the potential roles of the ephrin ligands and their Eph tyrosine kinase receptors during cranial motor neuron development and axon pathfinding, by investigating expression patterns of these molecules at relevant stages in the chick. We detected expression of EphA3 and EphA4 among trigeminal and facial motor neurons, at times when these neurons are projecting to their muscle targets in the branchial arches. Corresponding ephrin-A ligands for these receptors were found to be expressed in specific regions of the arches during the same period, implicating ephrin-mediated interactions in cranial motor axon pathfinding.

Animals↗

PubMed2000

Clinical applicability of the Ljubljana classification of epithelial hyperplastic laryngeal lesions.

The diagnosis, prognosis, and choice of treatment of various laryngeal lesions depends almost entirely on the interpretation of changes in the covering epithelium. These abnormalities, referred to as epithelial hyperplastic laryngeal lesions, have been graded according to the Ljubljana classification into simple, abnormal and atypical (risky epithelium) hyperplasia and carcinoma in situ. The aim of this study was to evaluate the clinical applicability and prognostic value of this classification and to determine the incidence of malignant transformation. A retrospective clinical-pathological analysis was performed in a series of 4167 patients with 4574 biopsies, treated from 1979 to 1994. Simple (benign prickle cell) hyperplasia was the predominant grade in nodules, polyps, Reinke's oedema, granulomas, and papillomas, accounting for 37.6-68.6% of cases. In chronic laryngitis, abnormal (benign basal cell) hyperplasia was predominant with 43.9% of cases. Atypical ('risky') hyperplasia was observed almost exclusively in patients with chronic laryngitis (16.1%) and papillomas (10.1%), and only exceptionally in patients with vocal cord nodules (0.9%) and Reinke's oedema (0.3%). The percentage of malignant transformation in atypical hyperplasia was 11.6% (13/112 patients in 2-12 years), while in simple and abnormal hyperplasia, it was 0.3% (8/2920 patients in 1.5-11 years). The data support the concept of the Ljubljana classification dividing epithelial hyperplastic laryngeal lesions into benign (simple and abnormal hyperplasia), potentially malignant (atypical hyperplasia) lesions and carcinoma in situ.

Adolescent↗

PubMed2000

The Ljubljana classification: a practical strategy for the diagnosis of laryngeal precancerous lesions.

There is no internationally accepted classification of epithelial hyperplastic laryngeal lesions (EHLL). The majority of current classifications follow criteria similar to those commonly used for cervical epithelial lesions. However, the different etiology of laryngeal cancer and its particular clinical and histologic features necessitate a grading system more appropriate to this region. The Ljubljana classification of EHLL was devised in 1971 to cater to this requirement. Detailed criteria for histologic grading in this classification were formulated by a working group on EHLL of the European Society of Pathology in 1999. The system recognizes four grades: simple and abnormal hyperplasia are benign categories; atypical hyperplasia ("risky" epithelium) is potentially malignant, and carcinoma in situ actually malignant. The main features by which the proposed grading system differs from other classifications are: 1. the distinction between benign and potentially malignant lesions; 2. the positive separation of carcinoma in situ from atypical hyperplasia; 3. the lack of prognostic significance for any surface keratin layer. The eventual outcome of EHLL patients so graded justifies the proposal for separating the lesions into a benign group, showing malignant transformation in only 0.9% of cases, from a potentially malignant group showing malignant transformation in 11% of cases. For diagnostically difficult cases, supplementary techniques such as those using morphometry, immunohistochemical and molecular biology are advised to improve the accuracy of diagnosis and predictions of their biological behavior.

Carcinoma in Situ↗

PubMed2000

Chromosomes 7,17 polysomies and overexpression of epidermal growth factor receptor and p53 protein in epithelial hyperplastic laryngeal lesions.

PURPOSE: To visualize directly a sequence of genetic changes underlying the entire spectrum of epithelial hyperplastic laryngeal lesions (EHLL) and laryngeal cancer by the use of non-isotopic in situ hybridization (ISH) for chromosomes 7 and 17 in correlation with overexpression of p53 protein and epidermal growth factor receptor (EGFR). The specific aim was to compare the results and prognostic significance between the two types of EHLL: isolated, mainly atypical hyperplasia or risky epithelium, and EHLL associated with squamous cell carcinoma (SCC). PATIENTS AND METHODS: 59 tissue specimens of EHLL obtained from 34 patients, graded according to the Ljubljana classification into simple (SH), abnormal (AbH) and atypical hyperplasia (AtH), and carcinoma in situ (CIS) were included in the study. Non-fluorescent ISH for chromosomes 7 and 17 was performed by biotinylated alpha-satellite DNA probes. Immunohistochemical staining for EGFR and p53 protein was analyzed on the same tissue samples. RESULTS: Polysomy for both chromosomes increased in correlation with progressive grades of EHLL. The most important finding was the statistically significant difference in chromosome copy numbers between the isolated AtH and AtH associated with SCC. Overexpression of EGFR and p53 protein was found in 61 (36/59) and 52% (31/59) of cases, respectively. The immunoreactivity for both markers increased with the grade of lesions, but the staining pattern was not so uniform in isolated EHLL. On the other hand, the immunoreactivity was expressed more constantly in EHLL adjacent to SCC. CONCLUSIONS: Numerical changes in chromosomes 7 and 17 might be associated with an upregulation of EGFR and p53 genes, and could contribute to critical events in laryngeal carcinogenesis. For daily practice, the cytogenetic and immunohistochemical analyses could be of assistance in distinguishing between low- and high-risk groups of AtH. However, the isolated forms of atypical hyperplasia need considerable further study by evaluating genetic changes with the described methods regarding their ultimate transformation to carcinoma.

Adult↗

PubMed2000

Laryngeal granuloma: characteristics of the covering epithelium.

The purpose of the present study was to evaluate the biological behaviour of the marginal epithelium, that proliferates and eventually covers laryngeal granulomas, and to reveal the applicability of the recently re-introduced Ljubljana classification when reporting reactive epithelial hyperplastic lesions. A retrospective clinical and histomorphological analysis was performed on 149 laryngeal granuloma biopsies. Epithelial changes were classified according to the Ljubljana classification into normal epithelium; simple, abnormal, or atypical hyperplasia; and carcinoma in situ. Atrophic epithelium, not evaluated separately in the Ljubljana classification, was additionally assessed. Simple hyperplasia was found in 98 cases (65.8 per cent), abnormal hyperplasia in seven (4.7 per cent), atrophic epithelium in 24 (16.1 per cent), and normal squamous epithelium in 20 (13.4 per cent). Atypical hyperplasia and carcinoma in situ were not observed. The results of our study clearly showed that the proliferation of the covering epithelium mostly in the form of simple hyperplasia, is entirely reactive and therefore reversible. No epithelial hyperplastic lesions were found that were previously described to be associated with an increased risk of malignant alteration, namely atypical hyperplasia and carcinoma in situ. However, since an initial growth of an invasive malignant neoplasm might macroscopically imitate the appearance of laryngeal granuloma, a histological examination in all aetiological forms of laryngeal granulomas is required. By clearly discerning the benign nature of epithelial changes in laryngeal granulomas, the recently re-evaluated and further formulated Ljubljana classification may also influence the clinical handling of patients.

Adolescent↗

PubMed2000

Rapid extraction of DNA from archival clinical specimens: our experiences.

The analysis of DNA extracted from archival clinical specimens using polymerase chain reaction represents the basis of a variety of research and diagnostic protocols in medicine. However, the selection of optimal DNA extraction method is critical if such an analysis is to be successful. Recently, we have evaluated a number of rapid DNA extraction protocols in order to find the most suitable method for routine processing of the most common archival materials in pathological and cytological laboratories: paraffin-embedded tissues and Papanicolaou- or Giemsa-stained smears. Our results demonstrate that rapid DNA extraction methods have comparable DNA extraction efficiencies with standard DNA isolation protocols on archival clinical specimens with the exception of Giemsa-stained smears.

Archives↗

PubMed2000

A mouse model of chronic bacterial lesions (a cotton trap) for studying oral bacteria-lymphocyte interactions.

We established a mouse model of chronic bacterial infection (cotton trap) to get a deeper insight into interactions between immune cells and bacterial strains, that are most commonly isolated from periapical processes. We have used flow cytometry to identify the presence of intracellular cytokines of activated T cells collected from cotton traps, previously infected with different strains of bacteria and implanted subcutaneously into the back of the mice. We provide an evidence that anaerobic bacteria (Bacteroides sp.) and nocardiae are more effective in inducing cytotoxic immunity and Th1 response compared to oral streptococci. Differences in immune response against anaerobic bacteria when compared to streptococci are probably dependent on some non-specific immune cell stimulation (e.g. by bacterial cell wall components), nevertheless the role of specific antigen-dependent immune mechanism can not be excluded.

Animals↗

PubMed1999

Criteria for grading in the Ljubljana classification of epithelial hyperplastic laryngeal lesions. A study by members of the Working Group on Epithelial Hyperplastic Laryngeal Lesions of the European Society of Pathology.

AIMS: To validate histological criteria for the grading of epithelial hyperplastic laryngeal lesions (EHHL) (dysplastic laryngeal lesions), we used a system that had been devised and tested in Ljubljana, Slovenia over many years and was felt to be more appropriate to laryngeal pathology than is the commonly-used model of intraepithelial neoplasia in the cervix. METHODS AND RESULTS: Vocal cord biopsies of 45 patients with a broad spectrum of EHLL were reviewed. Detailed histological criteria were formulated for each of the four grades of EHLL in the Ljubljana classification, comprising simple hyperplasia (benign spinous layer augmentation), abnormal hyperplasia (benign basal and parabasal layer augmentation), atypical hyperplasia (risky for malignancy) and carcinoma in situ (actually malignant, but without invasion). CONCLUSIONS: Using these criteria a high degree of concordance of histological diagnoses of grading levels for the Ljubljana classification was achieved between the pathologists of the Working Group. The system was found to be more precise for routine diagnostic work than the others in vogue. The different grades of the Ljubljana classification correspond to significantly different levels yielded in each grade by the semiobjective methods of quantitative morphometry and immunohistochemistry.

Epithelium↗