Comparison of PFA-100 closure time and template bleeding time of patients with inherited disorders causing defective platelet function.
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Adenosine Diphosphate↗
Biomedical subjects
C Kiss
Publications and source records attributed to C Kiss.
Analysis of NotI linking clones isolated from human chromosome 3 specific libraries.
We have partially sequenced more than 1000 NotI linking clones isolated from human chromosome 3-specific libraries. Of these clones, 152 were unique chromosome 3-specific clones. The clones were precisely mapped using a combination of fluorescence in situ hybridization (FISH) and hybridization to somatic cell or radiation hybrids. Two- and three-color FISH was used to order the clones that mapped to the same chromosomal region, and in some cases, chromosome jumping was used to resolve ambiguous mapping. When this NotI restriction map was compared with the yeast artificial chromosome (YAC) based chromosome 3 map, significant differences in several chromosome 3 regions were observed. A search of the EMBL nucleotide database with these sequences revealed homologies (90-100%) to more than 100 different genes or expressed sequence tags (ESTs). Many of these homologies were used to map new genes to chromosome 3. These results suggest that sequencing NotI linking clones, and sequencing CpG islands in general, may complement the EST project and aid in the discovery of all human genes by sequencing random cDNAs. This method may also yield information that cannot be obtained by the EST project alone; namely, the identification of the 5' ends of genes, including potential promoter/enhancer regions and other regulatory sequences
Animals↗
Identification of new tumor suppressor genes based on in vivo functional inactivation of a candidate gene.
As a step towards developing a new functional test for the identification of tumor suppressor genes, human wild type and mutant RB genes were expressed in the mouse A9 fibrosarcoma cell line under the transcriptional regulation of the tetracycline repressor using two new vectors: pLNCtTA and pETI. Following passage of the transfectants in immunodeficient SCID mice, the wild type RB gene was deleted or functionally inactivated already after the first passage in all 20 tumors tested. In contrast, a non-functional mutant RB gene was maintained in all 10 tumors studied. These results suggest that tests for the identification of tumor suppressor genes may be based on their functional inactivation in vivo, rather than on growth suppression.
Animals↗
[Normal values of vertebral heights in a representative population survey in Hungary].
The authors' aim was to derive Hungarian normal vertebral heights, height ratios and threshold values. The mean -3 SD of these ratios give them the threshold values for defining normal vertebraes. They examined the standardized vertebral morphometric measurements obtained in a cross-sectional population survey. Radiographs were taken according to standardized protocol and morphomeric measurements of anterior, central and posterior heights from thoracic 4 to lumbar 4 were made with a semiautomatic technique. The anterior, central, posterior I and posterior II height ratios were calculated for each vertebra. The mean and standard deviation of these ratios for each sex were derived using a statistical procedure to normalize the distribution. From the normally distributed vertebral height ratios the mean and standard deviation give us the threshold values for defining normal vertebraes. Anterior and central vertebral height ratios were smaller in males than females. The authors compared the ratios and threshold values in different European centers using the same method. The data confirm that vertebral height ratios vary between and within populations and the authors suggest that normal values for vertebral height ratios should be derived separately for males and females at each vertebral level. Having the normal values the knowledge of the Hungarian normal vertebral height ratios gives the possibility to carry on multicentre clinical, therapeutic and epidemiologic studies of vertebral deformity in Hungary. The authors suggest the widespread use of morphometry to evaluate vertebral osteoporosis because it can be done in every radiology unit, it is a cheap and easy method for measuring the bone mineral content.
Anthropometry↗
Biclonal chromosomal aberrations in a child with myelodysplastic syndrome.
Hematological malignancies and premalignant diseases are generally of monoclonal origin. The prognostic and therapeutic significance of finding two genetically independent clones remains to be determined. We followed a case of childhood myelodysplastic syndrome showing biclonal chromosomal abnormalities (+8, -7) by conventional cytogenetic examination and double target fluorescence in situ hybridization (FISH). A 7-year-old girl presented with Plaut-Vincent angina and leukopenia. The cytogenetic aberration of +8 was the first sign to suggest MDS. Serial bone marrow controls, prompted by a progressive clinical course detected myelodysplastic changes and a new clonal aberration (-7). The presence of -7 and +8 in two independent clones was verified by double-target FISH. While at diagnosis and during cytokine treatment more cells showed +8, after successful all-trans retinoic acid (ATRA) therapy, the clone with -7 predominated. Following allogeneic bone marrow transplantation the patient displayed donor-derived hematopoesis. Our data stress the significance of cytogenetic and FISH examinations in detecting specific genetic abnormalities and progressive clonal changes as an indicator and guideline for therapy. Different cell clones characterized by different genetic changes might be associated with different biologic features reflected in their response to treatment.
Angina Pectoris↗
A novel gene containing LIM domains (LIMD1) is located within the common eliminated region 1 (C3CER1) in 3p21.3.
Chromosomal deletions on 3p have been described in a large number of human tumors, suggesting the presence of a tumor suppressor gene(s). Using an experimental system, called the elimination test, we previously identified a 1 Mb segment, the common eliminated region 1 (C3CER1). C3CER1 was also covered by a PAC contig. Using the sequence of two overlapping PACs from C3CER1, we localized the human KIAA0028 cDNA, encoding the precursor of mitochondrial leucyl-tRNA synthetase. We also characterized a novel human LIM domain-containing gene (LIMD1) and its mouse ortholog (Limd1). LIM domains consist of a cysteine-rich consensus sequence containing two distinct zinc-binding subdomains, which mediate protein-protein interactions. The predicted protein sequences of the human and mouse genes reveal three LIM domains located at the C-terminal end, which indicates that they belong to the group 3 of the gene family encoding LIM motifs. We characterized the genomic structure of the human LIMD1 gene and assigned the mouse Limd1 gene to the chromosome 9F subtelomeric region. Both genes are ubiquitously expressed at the mRNA level. The LIM motif has been previously identified in many developmentally important factors from various eukaryotes. These factors have been shown to play a role in intracellular signaling, transcriptional regulation and cellular differentiation during development. The human C3CER1-located LIMD1 gene should therefore be further studied for its possible role in tumor suppression.
Amino Acid Sequence↗
Human herpesvirus 8 in hematologic diseases.
Human herpesvirus type 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV) is a new member of the g-herpesvirus family. It is an unusual herpesvirus in that it carries a large number of genes that encode oncoproteins or cell signaling proteins. In addition to being the causative agent of both HIV-associated and non-HIV-associated Kaposi's sarcoma this DNA tumor virus has been implicated in the pathogenesis of several diseases. These include multiple myeloma (MM), Waldenstöm's macroglobulinemia (WM), multicentric Castleman's disease (MCD), body cavity-based lymphoma (BCBL), and various other conditions such as sarcoidosis and pemphigus. While the causative role of the viral infection is fairly certain in the development of BCBL and multicentric Castleman's disease, HHV-8 may act through a different mechanism to induce plasma cell malignancies. It has been suggested though the finding is still controversial - that infection of bone marrow stromal dendritic cells by HHV-8 might be a key factor in the etiology and pathogenesis of monoclonal gammopathies. The aim of this review is to provide a short introduction into the tumorigenic potential of HHV-8 as well as to detail the available data and possible mechanisms on the involvement of this virus in different hematologic diseases.
Bone Marrow↗
[Analysis of activated cells in apical granuloma].
The ratio and in situ distribution of CD3+ T-lymphocytes, CD4+ and CD8+ subsets, CD14+ macrophages, CD56+ natural killer cells and CD25+ activated T-lymphocytes and CD68+ activated macrophages were determined in 20 chronic peripical granulomas by immunohistochemical method using monoclonal antibodies. CD3+ T-lymphocytes made up about 50% of the mononuclear cells. CD14+ macrophages were distributed all over the area but their proportion was much less that that of the T-lymphocytes. CD56+ natural killer cells made up a small proportion of the cells. The major proportion of the T-lymphocytes and macrophages were in activated stage within the lesion.
Antibodies, Monoclonal↗
Fluorescence in situ hybridization reveals trisomy 2q by insertion into 9p in hepatoblastoma.
Cytogenetics and fluorescence in situ hybridization (FISH) of a hepatoblastoma are presented. The results of standard chromosome analysis were as follows: 47,XY,+2,add(4)(q35),-9,+20[10]. FISH with the use of whole-chromosome paints revealed partial trisomy of the long arm of chromosome 2 by insertion into chromosome 9. Comparison of the G-banded metaphases with metaphase FISH led to a reinterpretation of the karyotype as: 47,XY,add(4)(q35),der(9)ins(9;2)(p22;q?21q?25),+20. This case supports previous observations that the critical region of trisomy 2 lies between 2q21 and 2qter and shows how partial trisomy 2q may evade detection in G-banded metaphases.
Child, Preschool↗
Interferons in pediatric oncology: end of the beginning or beginning of the end?
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Antineoplastic Agents↗
Distribution of interleukin-2 receptor alpha-chain and cells expressing major histocompatibility complex class II antigen in chronic human periapical lesions.
In situ distribution of CD2+ T-lymphocytes, CD4+ and CD8+ T-cell subsets, CD14+ macrophages, interleukin-2 receptor alpha-chain (IL-2R alpha) and class II major histocompatibility complex antigen (major histocompatibility complex class II, HLA-DR) expressing cells were determined in 14 chronic human periapical granulomas by immunohistochemical method using monoclonal antibodies. CD2+ lymphocytes were rather evenly distributed within the classical granulation tissue and comprised 55% of the mononuclear cells. Macrophages were distributed all over the periapical area, but their proportion was much less than that of T lymphocytes. Both small, lymphocyte-like mononuclear cells and larger mononuclear cells resembling macrophages displayed mild to strong circumferential staining with the anti-HLA-DR antibody. The majority of lymphocytes expressed IL-2R alpha indicating the activated state of T cells within the lesion.
Antibodies, Monoclonal↗
[2q21-qter trisomy in hepatoblastoma].
Cytogenetic findings and fluorescens in situ hybridization results of a hepatoblastoma of a boy of two and half years of age are presented. Cytogenetic analysis and fluorescens in situ hybridization technique were performed using tumor tissue obtained by biopsy. The direct culture was harvested after 16 hour colcemid treatment. The results of G-banding were as follows: 47,XY,add(4) (q26),-9,+20. There were considerable variation in the degree of condensation and hence in the number of visible G-bands both between metaphases and between homologous chromosomes in the same metaphases. Fluorescens in situ hybridisation were carried out by whole chromosome painting probes: 2,3,4, and 20. The karyotype of the malignant cells was adjusted accordingly: 47,XY,der(4)(q35),dir ins(9;2)(p22;q?21q?25),+20. The results confirm the most common primary chromosome abnormalities in hepatoblastoma are the following: trisomy 2, trisomy 20 and 4q structural rearrangement. Fluorescens in situ hybridization confirms the importance of trisomy 2q21-qter in hepatoblastoma. Authors recommend the use of fluorescens in situ hybridization to correct any tumor karyotype with difficult or ambiguous chromosome morphology.
Biopsy↗
[Prevalence of vertebral deformity in Hungary: the European Vertebral Osteoporosis Study].
Prevalence and distribution of vertebral deformity regarded as classic marker of osteoporosis are reported on the basis of the results of the first Hungarian cross-sectional population-based survey. The clinical-epidemiological project is conducted by the National Institute of Rheumatology and Physiotherapy in Hungary in the frame of the European Vertebral Osteoporosis Study which comprises 19 countries and 36 centres. A random sample of 324 females and 300 males aged 50 years and over stratified in 5-year age bands was recruited. Lateral spinal X-rays were evaluated centrally by two different morphometric methods. Based on the McCloskey-Kanis criteria the prevalence of all deformities was 16.7% in females and 18.7% in males. These values from Hungary have been considered high compared to the prevalence rates of other European countries, approaching, and in males exceeding, the highest rates gained from Sweden. In females the prevalence increased with age, men aged 50-59 years and women aged 75 years and over had higher prevalence of deformity compared to the other sex. In females vertebra thoracic 11, in males that of lumbar 3 were mostly affected, wedge deformities occurred most frequently. Extrapolating the results we can conclude that vertebral deformity found in both sexes similarly, affects approximately 500,000 individuals in Hungary along with the potential deterioration of quality of life. This enormous burden requires the consistent fulfillment of the National Osteoporosis Program and other preventive-curative strategies.
Aged↗
Diagnostic and prognostic significance of chromosome abnormalities in childhood acute lymphoblastic leukemia.
Current intensive chemotherapies cure about 70% of the children with ALL. On the other hand a significant number of the children are not cured despite intensive treatment. At the same time some highly curable patients are treated too intensively and suffer from unnecessary side effects of the chemo- and radiotherapy applied. In order to further improve the therapeutic results in this disease, we have to distinguish between the cases with a better and a worse prognosis. The initial karyotype (both numerical and structural chromosome abnormalities) proved to be one of the most reliable prognostic parameters, leading to the suggestion of developing genotype-specific therapies. Although the prognosis in patients with pseudodiploid karyotype is usually unfavorable, a significantly better prognosis can be observed in those with more than 50 chromosomes. Because the latter patients can achieve remission on a metabolite-based therapy, the toxic effects of more aggressive chemotherapy with anthracyclines and genotoxic agents can be avoided; thus, the reliable and accurate identification of patients with > 50 chromosomes is of particular importance. For this purpose three methods: chromosome analysis, DNA flow cytometry, and fluorescence in situ hybridization can be used. In 1993 it was decided to develop a comprehensive nationwide project in order to perform the initial genetic analysis of all ALL children diagnosed in the hematological/oncological centers of Hungary. Here the data obtained on 187 ALL patients diagnosed in the period from 1993 to 1995 are presented. In about 75% of patients (in 140 of 187) chromosome analysis was performed, in 78 cases (55.7%) successfully. The proportion of patients with abnormal karyotype was 36 of 78 (46.1%), and hyperdiploidy with more than 50 chromosomes was detected in 13 of 78 (16.6%) children. The lower ratio of hyperdiploid cases in our patients as compared to the data in the literature may be due to technical difficulties and the small number of patients studied, but it may reflect real geographic characteristics. Using flow cytometry, seven of 31 patients investigated (22.5%) proved to be hyperdiploid with a DNA index above 1.16. A higher ratio of hyperdiploid patients in this study calls attention to the significance of simultaneous application of the two methods. Taken together, 16 of 80 (20.0%) successfully studied patients proved to be hyperdiploid (> 50 chromosomes and/or DNA index above 1.16). The pattern of chromosome involvement in our study determined by chromosome analysis and/or FISH technique proved also to be different from the data of large international series. In addition to trisomies of chromosomes 4, 6, 10, 14, 17, 18, 21, and X, which are known to be the most frequently involved chromosomes, trisomies of chromosomes 3, 8, 11, and 13 were also observed with a high frequency. Comparison of survival curves of various cytogenetic subgroups showed a significant difference between diploid-pseudodiploid and diploid-hyperdiploid A (with 47-50 chromosomes) subgroups. No favorable prognosis of hyperdiploid patients (> 50 chromosomes) could be proved. Because of the small number of patients studied, prognostic differences of cytogenetic subgroups need further confirmation. The clinical and genetic differences observed, however, call attention to the necessity for further genetic studies of ALL patients in Hungary, because these differences may reflect real geographic characteristics and may be related to different environmental mutagen/carcinogen effects of the given geographic area. It is essential to determine whether or not these differences really exist and if they do to reveal the causes leading to these differences. In our view this is one of the routes by which the therapeutic results in childhood ALL can be further improved simultaneously with the avoidance of early and late toxicity of chemotherapy.
Child↗
[Prevalence and risk factors in diffuse idiopathic skeletal hyperostosis in a population sample in Hungary].
The aim of the study was to get some information on the epidemiology and etiology of DISH which is a frequent, chronic, benign musculoskeletal disease. In order to investigate the epidemiology of DISH the authors planned a population-based cross-sectional study and to investigate the etiology of the disease they planned a case-control study. The prevalence of DISH in Hungary in men over the age of 50 years is 5.8% and in women is 1.3%. In men DISH begins earlier in the lifetime and over the age of 65 years the prevalence increases rapidly in both sexes. In men throughout the life the disease is more common and more severe than in women. In the case-control study the authors investigated the association of the disease with risk factors as obesity, hyperuricemia, hypercholesterinemia, hypertriglyceridemia. Hyperuricemia was significantly more frequently found in DISH than in the control group. In the name of DISH the word "idiopathic" is questionable because apart from the known glucose metabolic imbalance other metabolic abnormalities (uric acid) could be found. There might be a complex metabolic disturbance in the etiology of DISH.
Age Factors↗
[Thrombocyte dysfunction in children with albinism].
Seven children with albinism were examined for haemorrhagic diathesis. In 6 patients coagulation screening tests (prothrombin time, activated partial thromboplastin time, thrombin time) were normal, in 1 patient prolongation of activated partial thromboplastin time due to mild factor XI deficiency was found. Platelet counts were in the reference range, however, the template bleeding time of 6 out of 7 patients was prolonged. Evaluation of platelet aggregation and secretion in a lumi-aggregometer demonstrated that only the child with normal bleeding time had normal platelet function, and 6 children with prolonged bleeding time had impaired aggregation and release reaction. Five out of these 6 patients had severe decrease of ATP secretion even when high dose of thrombin was used as agonist. The number of dens granules in the platelets of these patients, as measured by the uptake of mepacrine, was significantly less than in normal controls. These findings clearly suggested storage pool deficiency. In one of these patients storage pool deficiency was associated with mild factor XI deficiency. The high frequency of haemorrhagic diathesis in albino children emphasizes, the importance of the screening of patients with albinism for bleeding diathesis.
Adolescent↗
Assignment of the ARHA and GPX1 genes to human chromosome bands 3p21.3 by in situ hybridization and with somatic cell hybrids.
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Chromosome Mapping↗
[Megakaryocytic thrombopenic purpura associated with enamel hypoplasia].
Patients with platelet disorders usually bleed into superficial sites such as the skin, mucous membranes, genitourinary tract and gastrointestinal tract caused by thrombocytopenia or thrombocyte dysfunction. Thrombocytopenia is caused by one of three mechanisms-decreased marrow production, increased splenic sequestration, or accelerated destruction of platelets. We report a 9-year-old male patient with thrombocytopenic purpura, dyserythropoetic anaemia, freckles on the skin and nanosomia, resembling Fanconi's (constitutional) anaemia. Although many patients with constitutional anaemia own other bony abnormalities, it was not found in this case. On the other hand, the patient showed enamel hypoplasia. To our knowledge, this association has never been reported before. Laboratory diagnosis, clinical findings, dental abnormalities and treatment are presented in details.
Abnormalities, Multiple↗