Biomedical subjects

Mara Dominis

Publications and source records attributed to Mara Dominis.

At least 19 recordsLinked to original sources

PubMed2007

MALT1, BCL10 and FOXP1 in salivary gland mucosa-associated lymphoid tissue lymphomas.

In view of the certain anatomic site-dependent frequency of chromosomal translocations involved in extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) pathogenesis, 17 salivary gland MALT lymphoma cases were analyzed for MALT1 and FOXP1 translocations. B cell CLL/lymphoma 10 (BCL10) and forkhead box PA (FOXP1) protein expression were studied by immunohistochemistry and translocations identified using fluorescence in situ hybridization (FISH)-specific probes FOXP1, t(11;18)(q21;q21)/API2-MALT1 and t(14;18)(q32;q21)/IgH-MALT1. None of the 11 analyzed cases showed FOXP1 rearrangement or amplification. The t(11;18) was present in five of 13 cases and the t(14;18) in three of 13 cases. MALT1 translocations were mostly mutually exclusive except in a single case. FOXP1 protein expression showed differences in the proportion of tumor cells with nuclear expression but not in their intensity, with the exception of one case where very intense nuclear staining was noted. BCL10 nuclear expression was present in four of 17 cases, two of which lacked t(11;18). Our results suggest that MALT1-specific translocations and FOXP1 rearrangements are not commonly involved in pathogenesis. A case with strong FOXP1 protein expression indicates the possibility that the upregulation of FOXP1 expression is significant in a small subset of salivary gland MALT lymphomas. Also a single case in which both MALT1 translocations were present indicates that these are not always mutually exclusive.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Gene replacement reveals a specific role for E-cadherin in the formation of a functional trophectoderm.

During mammalian embryogenesis the trophectoderm represents the first epithelial structure formed. The cell adhesion molecule E-cadherin is ultimately necessary for the transition from compacted morula to the formation of the blastocyst to ensure correct establishment of adhesion junctions in the trophectoderm. Here, we analyzed to what extent E-cadherin confers unique adhesion and signaling properties in trophectoderm formation in vivo. Using a gene replacement approach, we introduced N-cadherin cDNA into the E-cadherin genomic locus. We show that the expression of N-cadherin driven from the E-cadherin locus reflects the expression pattern of endogenous E-cadherin. Heterozygous mice co-expressing E- and N-cadherin are vital and show normal embryonic development. Interestingly, N-cadherin homozygous mutant embryos phenocopy E-cadherin-null mutant embryos. Upon removal of the maternal E-cadherin, we demonstrate that N-cadherin is able to provide sufficient cellular adhesion to mediate morula compaction, but is insufficient for the subsequent formation of a fully polarized functional trophectoderm. When ES cells were isolated from N-cadherin homozygous mutant embryos and teratomas were produced, these ES cells differentiated into a large variety of tissue-like structures. Importantly, different epithelial-like structures expressing N-cadherin were formed, including respiratory epithelia, squamous epithelia with signs of keratinization and secretory epithelia with goblet cells. Thus, N-cadherin can maintain epithelia in differentiating ES cells, but not during the formation of the trophectoderm. Our results point to a specific and unique function for E-cadherin during mouse preimplantation development.

Animals↗

PubMed2006

Primary mediastinal large B-cell lymphoma: a single-center study of clinicopathologic characteristics.

Primary mediastinal large B-cell lymphoma (PMLBCL) is a subset of LBCL with unique clinicopathologic features. Some studies have raised the question of differences in biological features and clinical course among patients from different parts of the world. We conducted a retrospective clinicopathologic analysis of 24 patients with PMLBCL from a single center in Croatia. We also conducted the first investigation of the frequency of lymphotropic viruses human herpesvirus 6 (HHV-6) and HHV-8 in lymphoid lesions of this disease. The clinical characteristics of the patients were as expected, with high International Prognostic Index scores, elevated serum lactate dehydrogenase (LDH) levels, and bulky disease being adverse prognostic factors. Only 6 patients (25%) showed CD30 expression, and Bcl-6 protein expression was, in our series, prognostically favorable (P = .0401). One patient's tumor had detectable HHV-6 genome sequence, but no HHV-8 sequences were detected in any tumors. Two thirds of the patients received CHOP chemotherapy (cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone) with a relatively low complete remission rate (43.8%; median follow-up, 33.8 months). This study confirmed the moderate preponderance among PMLBCL patients of young females with B symptoms and elevated LDH levels. The CHOP regimen proved effective as first-line therapy only in patients with limited disease. Therefore, other third-generation chemotherapy protocols may be considered for treatment, especially in patients with bulky and advanced disease.

Adult↗

PubMed2006

The place and role of serologic methods in detecting Helicobacter pylori infection.

The aim of the study was to determine the place and role of serologic methods in detecting Helicobacter pylori (H. pylori) infection, on the basis of estimated enzyme-linked immunosorbent assay (ELISA) and complement fixation test (CFT) sensitivity and specificity. A total of 549 patients were included in the study. ELISA and CFT as serologic methods were compared with invasive methods (rapid urease test--CLO test, culture, histology). The sensitivity of serologic methods was above 90%, and their specificity was around 80%. Study results confirmed the value, reliability and usefulness of serologic methods in the detection of H. pylori infection.

Adult↗

PubMed2005

Croatian implementation of a computer-based teaching program from the University of Kansas, USA.

AIM: To determine whether the students enrolled in the computer-based teaching program would take the final examination in pathology earlier than those who studied according to the previous traditional program. METHODS: The study included all medical students enrolled in the pathology course at the Zagreb University School of Medicine, Zagreb, Croatia, between 1995/96 and 2000/01 academic years. In the fall of 1998, computer-based teaching program from the University of Kansas was implemented at the Zagreb University School of Medicine, with 48 of the class of 225 students (20%) randomly enrolled in the program. The remaining 80% of students of the same class were enrolled in the traditional teaching program used at the Zagreb University School of Medicine. We compared the success of these two groups of students at the final pathology examination in the first term. Following this initial observational period, all students in the next two years (1999/00 and 2000/01), were enrolled in the computer-based teaching program. Pass rates of these students at the final examination taken in the first term were compared with the pass rates of students who studied according to the traditional teaching program during the period from 1995 to 1998. RESULTS: In 1998, 58.3% of students from the computer-based teaching program group chose to take the final examination in the first term, compared with only 32.2% of students from the traditional teaching program group (chi(2) (1)=10.97, P<0.001). Students in the computer based program had better final examination mean scores (-/+ standard deviation) than students in the traditional program (81.9-/+9.8 and 73.3-/+14.2, respectively; t=2.908, P=0.005). Upon the implementation of the computer-based teaching program for the entire class in 1999 and 2000, the number of students taking the final examination in the first term increased more than we expected on the basis of the data from the academic years 1995 to 1998 (chi(2) (5)=39.60, P<0.001). CONCLUSION: The computer-based program introduced at the Zagreb University School of Medicine in 1998 had a positive effect on medical students, as evidenced by the fact that more students chose to take the final pathology examination in the first term and more of them passed the examination in the first attempt than those in the traditional teaching program.

Computer-Assisted Instruction↗

PubMed2005

Bone marrow lymphoid aggregates in malignant lymphomas.

AIM: To examine the usefulness of molecular analysis of IgH gene rearrangement in assessment of clonality in bone marrow biopsies with lymphoid aggregates (LA) and/or nodular lymphoid hyperplasia (NLH) in patients with different subtypes of malignant lymphomas. METHOD: Five hundred and twenty nine samples of bone marrow biopsies, taken in a staging procedure at the time of the initial presentation of illness, were processed routinely. Results were grouped in positive, negative, and cases with LA or NLH. In 43 samples with present LA/NLH, polymerase chain reaction (PCR) analysis of the CDR3 region of immunoglobulin heavy chain gene (IgH) for B-cell clonality was performed. RESULTS: Bone marrow malignant lymphoma infiltrates were present in 33.8% of lymphoma cases. The incidence of LA/NLH in bone marrow was 8.1%. LA/NLH were more frequently found in patients with extranodal disease and aggressive subtypes of B cell non-Hodgkin lymphoma (B-NHL), but there was no significant difference among the incidence according to the biological behavior of malignant lymphoma (P=0.232). Results of IgH-CDR3 region PCR analysis showed a monoclonal pattern in 1 case of Hodgkin lymphoma and in 1 control case, an oligoclonal pattern in 2 cases of extra nodal B-NHL, whereas all other had polyclonal. CONCLUSION: The results support our initial hypothesis that LA/NLH could be differentiated from malignant infiltrates in bone marrow staging procedure of malignant lymphoma by topographic pattern and histocytomorphology of LA/NLH. Surprisingly, our patients with aggressive B-NHL, nodal, as well as extranodal, had LA/NLH in bone marrow biopsies more often than patients with indolent B-NHL.

Biopsy↗

PubMed2004

T- and B-cell clonality and frequency of human herpes viruses-6, -8 and Epstein Barr virus in angioimmunoblastic T-cell lymphoma.

Angioimmunoblastic T-cell lymphoma (T-AIL) is a peripheral T-cell lymphoma of unknown etiology. Previous clonality studies have shown a heterogeneous composition of this disease with varying restrictions of B- and T-cell populations in the tumour. For the first time in a single study and in the same pathological materials, we have analysed, lymphoid cell clonality and occurrence of human herpes viruses and Epstein Barr virus. Of 18 cases 12 (66.6%) had clonal T- and three (16.6%) had clonal B-cells. Presence of the lymphotropic viral genome of HHV6 was detected in four of 18 lymph node biopsies from T-AIL patients (22%), all were TCRgamma clonal. No HHV8 were found. Epstein Barr genome was found in 40% of cases. There was no significant association between T-cell clonality and HHV-6 or EBV infection, or between B-cell clonality and any virus infection. We conclude that T-AIL is a biologically and clinically heterogeneous entity whose true nature remains to be clarified.

B-Lymphocyte Subsets↗

PubMed2004

[Presence of bcl-2 and p53 proteins in patients with non-Hodgkin's lymphoma at Zadar General Hospital].

AIM: The presence of bcl-2 and p53 was retrospectively analyzed in 37 previously untreated patients, diagnosed with non-Hodgkin's lymphoma in the period between 1980 and 1998. PATIENTS AND METHODS: According to all positivity in analyzed preparations, all lymphoma were divided into three categories: negative (-) with less than 1 per cent of positive tumor cells for the above-mentioned oncogenes; moderately positive (+) with 1 to 50 per cent of positive tumor cells, and extremely positive (+ +) with over 50 per cent of tumor cells. RESULTS: Twenty-seven (73%) patients with non-Hodgkin's lymphoma were bcl-2 negative, seven (19%) were bcl-2 positive (+), and only one (3%) patient was extremely positive for bcl-2. Bcl-2 was present in follicular lymphomas regardless of the intensity, whereas its presence was not recorded in other subtypes of indolent lymphomas. Bcl-2 was moderately positive (+) in six of 11 patients with follicular lymphoma. As for aggressive lymphomas, bcl-2 was present in three patients, one (3%) of them diagnosed with follicular lymphoma grade III and moderately positive (+) bcl-2. The other two patients were diagnosed with diffuse large B-cell lymphoma, with moderate (+) and extreme (+ +) bcl-2 positivity recorded in one patient each. P53 was negative (-) in six (16%), positive (+) in 27 (73%) and extremely positive (+ +) in four (11%) patients. Positive p53 was found in patients with non-Hodgkin's lymphoma regardless of the level of malignancy. CONCLUSION: This study demonstrated that the expression of oncogenes could be determined in the archival material of lymph node biopsy. The results on oncogene expression were consistent with the expected incidence based on other characteristics of the study population.

Adult↗

PubMed2003

Angiotensin I-converting enzyme is expressed by erythropoietic cells of normal and myeloproliferative bone marrow.

It is proposed that a locally active, intrinsic renin-angiotensin system (RAS) exists in the bone marrow (BM) and plays a role in regulating haematopoiesis. Angiotensin II type I receptor has been detected on erythroid burst-forming unit-derived cells; its antagonist losartan and angiotensin I-converting enzyme (ACE) inhibitors can suppress erythropoiesis. The possible role of ACE/RAS in BM was investigated by evaluating ACE expression in normal BM, several myeloproliferative disorders and myelodysplasia. Immunohistochemical studies showed that erythroid elements expressed ACE protein in both normal and disturbed haematopoiesis. The presence of ACE in erythroid cells suggests another mechanism for direct ACE inhibitor activity in erythropoiesis.

Anemia, Refractory↗

PubMed2003

[Non-Hodgkin's lymphoma: clinical symptoms, therapy and prognosis in 37 patients].

Clinical characteristics and prognostic factors in 37 patients with the diagnosis of non-Hodgkin's lymphoma made during the 1980-1998 period were retrospectively analyzed. Median age was 70 years, and 70% of patients were aged > 60. The disease was classified according to REAL classification. Twenty-seven (73%) patients had B cell lymphoma, and 10 (27%) patients had T cell lymphoma. Indolent lymphoma was diagnosed in 14, and aggressive lymphoma in 23 patients. Performance status as assessed according to the Eastern Cooperative Oncology Group scale was 0 or 1 in 73%, and worse in 27% of patients. The presence of B symptoms was recorded in 49% of patients. Lymph nodes exceeding 5 cm in size were found in 35% of patients. Erythrocyte sedimentation rate > 40 mm/h was recorded in 43%, and hemoglobin values < 125 mg/L in 73% of patients. Leukocytes were within the normal limits, i.e. below 10 x 10(9)/L, in 81%, whereas lymphocytes were within the normal limits in 86% of patients. Thrombocytopenia was recorded in 24%, and bone marrow infiltration at the time of diagnosis in 65% of patients. Complete or partial response rate was achieved by first-line therapy in 73% of patients, whereas 27% of patients failed to respond or their condition worsened. Median of the expected survival was 60 months for indolent lymphomas and 29 months for aggressive non-Hodgkin's lymphoma. Statistically relevant parameters for complete response in univariate analyses are performance status of the patient, International Prognostic Index and platelet count. In multivariate analysis, the only statistically independent prognostic factor is serum lactate dehydrogenase concentration (p = 0.037). The study confirmed the prognostic relevance of the parameters of the patient general condition according to the World Health Organization scale, International Prognostic Index and platelet count for complete response in univariate analyses. The only independent prognostic factor for the survival was serum lactate dehydrogenase concentration. The prognostic value of the International Prognostic Index was also confirmed.

Adult↗

PubMed2002

Diffuse large B-cell lymphoma and its variants.

According to the World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues, diffuse large B-cell lymphoma comprises about 40% of adult cases of non-Hodgkin s lymphoma. It consists of the following morphological variants: 1) centroblastic (with or without multilobulated nuclei); 2) immunoblastic (>90% of immunoblasts); 3) T cell/histiocytes rich; and 4) anaplastic. Rare morphological variants plasmablastic type, mediastinal (thymic) diffuse large B-cell lymphoma, intravascular, and primary effusion B-cell lymphoma are considered distinct variants of diffuse large B-cell lymphoma due to their unique topographic presentation and clinical behavior, as well as immunophenotypic and genetic characteristics. T-cell/histiocyte-rich B-cell lymphoma is morphologically characterized by up to 25% of large neoplastic B cells and 75-90% of reactive, non-neoplastic T cells. Mediastinal (thymic) diffuse large B-cell lymphoma is considered a subtype of diffuse large B-cell lymphoma arising in the mediastinum, with distinctive morphological, immunohistochemical, genotypic, and clinical features. Mediastinal diffuse large B-cell lymphoma is an aggressive disease with poor outcome, which probably originates from thymic B cells at the terminal stage of differentiation. During the 1997-2001 period, 720 patients were diagnosed with non-Hodgkin s lymphoma in our institution. Out of 101 (14%) patients with diffuse large B-cell lymphoma, 17 had T-cell-rich B-cell lymphoma and their median survival was less than 20 months, with no difference regarding sex, bone marrow involvement, CD30 positivity, or histiocytic component of the tumor. Twenty out of 101 patients had mediastinal B-cell lymphoma and their median survival was 21 months, with sex or degree of necrosis of the involved lymph node having no impact on survival. We studied the frequency of bcl-2 gene rearrangement in fusion with immunoglobulin receptor gene of t(14;18) and found no such event among 20 of our patients with mediastinal diffuse large B-cell lymphoma. Despite extensive efforts and constant progress in our understanding of non-Hodgkin s lymphoma pathogenesis, the diffuse large B-cell lymphoma group remains heterogeneous entity awaiting further pathological and clinical stratification.

Adult↗

PubMed2002

[Helicobacter pylori--introduction and review of research].

The discovery of Helicobacter pylori has revolutionized the pathophysiological and clinical approach to gastric and duodenal ulcer. Since the first paper identifying H. pylori was published only 17 years ago, it has been found out that this bacterium causes probably the commonest human infection. Numerous papers published so far have confirmed causal relationship between H. pylori infection and gastritis, duodenal ulcer, gastric ulcer and gastric cancer. If any recent achievement in the world of medicine is to be called revolutionary, then it is the discovery of the role of a spiral bacterium in the etiopathogenesis of gastritis, gastric ulcer, duodenal ulcer and gastric cancer. The discovery of the role of Helicobacter pylori has entirely changed our views and approach to the treatment of patients with stomach disorders. Not only do these discoveries change our actions, but above all our way of thinking. Almost routine diagnostics and treatment of gastritis, gastric ulcer or cancer has been replaced by studies in epidemiology, isolation and eradication of a single bacterium.

Duodenal Ulcer↗

PubMed2002

[Epidemiology of Helicobacter pylori infection].

About 50% of adults in the developed and 80-90% in the developing countries are estimated to be infected by Helicobacter pylori. Being 68% nationally, this rate is higher in the northern continental parts of Croatia, which also have higher gastric cancer rates. Low socio-economic status, poor living conditions in childhood (the age when Helicobacter pylori is typically acquired), and exposure to the stomach content of an infected person are risk factors for Helicobacter pylori. Most of the infected are symptomless, with 10 to 20% subsequently developing the disease, and this mainly from peptic ulcer, asymptomatic chronic gastritis and chronic dyspepsia. Less than 5/10,000 become affected with adenocarcinoma, MALT lymphoma or primary non-Hodgkin's gastric lymphoma. Helicobacter pylori is under intensive study for possible association with other diseases. As transmission route of the infection is still unclear, any mechanism allowing the bacteria entry into a non-infected individual's stomach is probably a possibility. In addition to improved socio-economic status, eradication or vaccination may be contributors to the reduction in the number of the infected.

Adolescent↗

PubMed2002

[Helicobacter pylori--bacterial characteristics].

Helicobacter pylori lives in the gastric mucosa of about half of world population. H. pylori is a gram-negative, microaerophilic, facultatively acidophilic rod, very sensitive to drying and usual disinfectants. H. pylori strains show great genetic variability, the main mechanism of this phenomenon being in vivo genetic recombination. The principal virulence factors are: vacuolating cytotoxin, enzyme urease, motility, adhesive molecules on the cell surface, catalase and superoxide-dysmutase, receptor for human lactoferin and factors which promote proinflammatory cytokine secretion. Strains of H. pylori are sensitive to ampicillin and tetracycline; resistance to macrolide antibiotics is 7-15% in different parts of the world, and to metronidazole is 7-50% or even more. Because in vitro sensitivity of H. pylori is the most important factor for successful therapy, it is necessary to monitor this sensitivity continuously in a particular area.

Drug Resistance↗

PubMed2002

[Diagnosis of Helicobacter pylori infection].

The diagnostics of Helicobacter pylori infection is now one of the most important aspects of the diagnosis of various gastroduodenal diseases. New data have shown that Helicobacter pylori is a causative agent of peptic ulcer disease and an important factor in cancer development. Numerous diagnostic tests are now available. They can be divided into two groups: invasive and noninvasive tests. All invasive test methods are based on endoscopic examination during which biopsy specimens are obtained for direct (histological analysis, isolation) or indirect (urease test) diagnosis of Helicobacter pylori infection. Noninasive methods reveal the presence of Helicobacter pylori by measuring the activity of urease (urea breath test), then by confirming the presence of antibodies in the serum or saliva of the infected person or by confirming the presence of Helicobacter pylori antigens in the feces.

Adult↗

PubMed2002

[Helicobacter pylori--bacteriologic diagnosis and antibiotic sensitivity tests].

Bacteriological diagnosis of Helicobacter pylori consists of culture from gastric biopsies, gastric juice, faeces and from specimens obtained from oral cavity, antigen stool assay and molecular diagnostic methods. In routine work culture is done from gastric biopsies. Other specimens are usually cultivated for research purposes. Culture constitutes the most specific way to establish the diagnosis of H. pylori infection. One of the major advantages of culture is that it allows sensitivity testing to drugs used in therapy. Culture also allows characterisation of H. pylori. Antigen stoll assay is a non-invasive diagnostic procedure, which should be evaluated. Molecular methods have confirmed their potential for epidemiological research and for the detection of resistant H. pylori, especially for macrolides. The clinical settings, local availability and economic considerations should guide use of bacteriological diagnostic methods.

Bacteriological Techniques↗

PubMed2002

[Serodiagnosis of Helicobacter pylori infection].

Infection with Helicobacter pylori induces antibodies, but these are not able to eradicate the bacterium from the gastric mucosa. Enzyme linked immunosorbent assay is the laboratory based method and most commonly used to measure qualitatively and quantitatively anti-Helicobacter pylori antibodies of different immunoglobulin classes in almost all infected patients. Quantitative serological tests are useful in the follow-up of eradication therapy. Serology is the method of choice in population studies and in the retrospective analysis of stored serum samples to study the natural course of this chronic infection.

Antibodies, Bacterial↗

PubMed2002

[Morphology of gastritis and Helicobacter pylori infection].

Helicobacter pylori infection almost invariably results in chronic gastritis. The Sydney System (1990) emphasised the importance of combining topographical, morphological and etiological aspects in attempt to make clinical useful diagnosis of chronic gastritis. The aims of revised Sydney System in Houston (1994), Texas, were to improve terminology of chronic gastritis emphasising distinction between nonatrophic and atrophic gastritis, and in addition to determinate special forms of gastritis. The special forms of gastritis were described and diagnostic criteria were provided. Principles and grading of histological division of Sydney System were only slightly modified, grading being improved by the provision of a visual scale. Endoscopy and histological findings of 1062 patients from University Hospital Merkur were compared to evaluate the value of endoscopic division of Sydney System, and the modified grading proposed by Houston classification. There was no correlation between endoscopic and histological findings. Localisation of inflammatory cells was either 1) superficial or 2) diffuse in the mucosa, respectively. In Helicobacter pylori positive patients the most common finding was chronic active gastritis, and in Helicobacter pylori negative superficial and inactive chronic gastritis.

Biopsy, Needle↗