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PubMed2007

[Peripheral NK/T-cell lymphoma].

Peripheral T-cell lymphomas comprise 8% of the malignant lymphomas in Germany. About 25% of these cases present primarily in extranodal localizations. Such localizations are typical for the respective disease and form the basis for the classification of extranodal peripheral T-cell lymphoma. The morphology, immunophenotype and lineage specificity of the tumor cells (originating from T- or NK-cells) is only secondary for the classification. Extranodal NK/T-cell lymphomas of the nasal type are characterized by an angiocentric growth pattern and large confluent areas of necrosis. In addition, there is a clonal infection by Epstein-Barr virus in the T-lymphocytes. In the differential diagnosis, B-cell lymphomas are more frequent at all localizations than T- or NK-cell lymphomas.

Diagnosis, Differential↗
PubMed2004

Comparative proteomics of the Mycobacterium leprae binding protein myelin P0: its implication in leprosy and other neurodegenerative diseases.

Mycobacterium leprae, the causative agent of leprosy invades Schwann cells of the peripheral nerves leading to nerve damage and disfigurement, which is the hallmark of the disease. Wet experiments have shown that M. leprae binds to a major peripheral nerve protein, the myelin P zero (P0). This protein is specific to peripheral nerve and may be important in the initial step of M. leprae binding and invasion of Schwann cells which is the feature of leprosy. Though the receptors on Schawann cells, cytokines, chemokines and antibodies to M. leprae have been identified the molecular mechanism of nerve damage and neurodegeneration is not clearly defined. Recently pathogen and host protein/nucleotide sequence similarities (molecular mimicry) have been implicated in neurodegenerative diseases. The approach of the present study is to utilise bioinformatic tools to understand leprosy nerve damage by carrying out sequence and structural similarity searches of myelin P0 with leproma and other genomic database. Since myelin P0 is unique to peripheral nerve, its sequence and structural similarities in other neuropathogens have also been noted. Comparison of myelin P0 with the M. leprae proteins revealed two characterised proteins, Ferrodoxin NADP reductase and a conserved membrane protein, which showed similarity to the query sequence. Comparison with the entire genomic database (www.ncbi.nlm.nih.gov) by basic local alignment search tool for proteins (BLASTP) and fold classification of structure-structure alignment of proteins (FSSP) searches revealed that myelin P0 had sequence/structural similarities to the poliovirus receptor, coxsackie-adenovirus receptor, anthrax protective antigen, diphtheria toxin, herpes simplex virus, HIV gag-1 peptide, and gp120 among others. These proteins are known to be associated directly or indirectly with neruodegeneration. Sequence and structural similarities to the immunoglobin regions of myelin P0 could have implications in host-pathogen interactions, as it has homophilic adhesive properties. Although these observed similarities are not highly significant in their percentage identity, they could be functionally important in molecular mimicry, receptor binding and cell signaling events involved in neurodegeneration.

Amino Acid Sequence↗
PubMed1999

Endoprosthetic reconstruction for malignant upper extremity tumors.

Between December 1980 and December 1992, 59 patients underwent 60 reconstructions with endoprostheses after resection of malignant tumors in the upper extremity. There were 32 male patients and 27 female patients, with a mean age of 33 years (range, 3-83 years). The type of reconstruction was based on the location of the primary tumor site. The histologic diagnoses included osteosarcoma, chondrosarcoma, Ewing's sarcoma, malignant fibrous histiocytoma, soft tissue sarcoma, and fibrosarcoma of bone. Most of the patients had Stage IIB disease (N = 38), as established by the Musculoskeletal Tumor Society classification. An additional six patients had metastatic tumors to the upper extremity. Twenty-seven of 59 patients died of disease progression. Two patients died of other causes (chronic leukemia, human immunodeficiency virus infection). The 30 survivors had a mean followup of 90 months (range, 60-170 months). The Musculoskeletal Tumor Society functional analysis for the patients with a minimum 2-year followup (N = 41) averaged 74%. Sixteen of the 59 (27%) patients had local complications. Problems related to mechanical failure and infection were managed successfully with second operation. Amputation was rare, occurring in three of 60 (5%) patients and was related only to local recurrence. Endoprosthetic reconstructions of the upper extremity after tumor resections have proven to be successful.

Adolescent↗
PubMed2006

HIV-1 coreceptor preference is distinct from target cell tropism: a dual-parameter nomenclature to define viral phenotypes.

HIV-1 infection of cells is mediated by engagement between viral envelope glycoproteins (Env) and a receptor complex comprising CD4 and one of two chemokine receptors, CCR5 and CXCR4, expressed on the surface of target cells. Most CD4+-transformed T cell lines express only CXCR4, but primary lymphocytes and macrophages, the main cellular targets for infection in vivo, express both coreceptors. Cell- and viral strain-specific utilization of these coreceptor pathways, rather than coreceptor expression per se, regulates lymphocyte and macrophage entry and tropism. Virus use of coreceptor[s] (R5, X4, or R5 and X4) and its target cell tropism (lymphocytes, macrophages, and/or transformed T cell lines) are related but distinct characteristics of Envs. A comprehensive classification schema of HIV-1 Env phenotypes that addresses both tropism and coreceptor use is proposed. Defining Env phenotype based on both parameters is important in the development of entry inhibitors and vaccines, for understanding changes in Env that evolve over time in vivo, and for discerning differences among viral species that underlie aspects of pathogenesis and transmission. Recognizing how tropism is related to, yet differs from, coreceptor selectivity is critical for understanding the mechanisms by which these viral characteristics impact pathogenesis.

CD4-Positive T-Lymphocytes↗
PubMed1976

[Epithelial tumor-like changes, precancerous conditions and skin neoplasms (standardization study)].

A retrospective study of bioptic material was used to design the following outline of a histological classification of epithelial skin tumours tentatively compared with handbooks published by the WHO (1) and AFIP (2): I. Tumour-like changes: 1. senile verruca (mixed, acanthotic, melanoacanthotic, hyperkeratonic, reticular, inverted). 2. Virus verrucosities (v. vulgaris, v. plana, c. accuminatum, molluscom contagiosum). 3. Hamartogenic verrucosities (naevus verrucosus, n. comedonicus, fibroepithelial papilloma. 4. Genetically undefined verrucosities (acanthosis nigricans, light cell acanthoma, verrucous dyskeratosis). 5. Cysts (atheroma, epidermoid cyst, dermoid cyst, others). 6. Unclassified. II. Precanceroses: 1. Pseudoepitheliomatous hyperplasis, 2. keratosis senilis, 3. Radiation dermatosis, 4. Unclassified. III. Epithelial tumours A. From surface epithelium 1. Spinocellular carcinoma (basic type, anaplastic, adenoid, sarcomatoid, clear cell carcinoma, intraepidermal). 2. Basocellular carcinoma: a) varieties derived from surface epithelium (intraepithelial, superficial, solid, cystic, invasive), b) varieties with adenoid features (cylindromatous, fibroepithelia), c) varieties with trichoepithelial features (keratinizing, pigment-type, clear cell type), d) naevus varieties (basocellular naevi). 3. Spinobasocellular carcinoma. 4. Unclassifiable. B. Sweat gland tumours: 1. syringocystadenoma papilliferum, 2. hidradenoma papillare, 3. nodular hidradenoma (eccrine spiradenoma, eccrine acrospiroma, myxochondroepithelioma, myoepithelioma, mucinous epithelioma), 4. syringoma, 5. eccrine cylindroma, 6. hidrocystoma, 7. eccrine poroma, 8. carcinomas (so called extramammary Paget carcinoma), 9. unclassifiable. C. Sebaceous gland tumours: 1. adenoma sebaceum, 2. carcinoma sebaceum, 3. quasi tumours (naevus sebaceus, Pringle's hamartoma, steatocystoma multiplex, hyperplasia), 4. unclassifiable. D. Trichoepithelial tumours: 1. trichofolliculoma, 2. follicular poroma, 3. keratoacanthoma, 4. tricholemoma, 5. pilomatrixoma, 6. trichogenic adnexal tumour, 7. trichoepithelioma, 8l unclassifiable.

Aging↗
PubMed1994

[Evaluation of liver biopsies in chronic hepatitis].

New knowledge of the different hepatitis viruses and of the evolution of chronic viral hepatitis has necessitated review of the nomenclature of chronic hepatitis and of its histological categories. Some hepatologists now prefer to use a primarily aetiological classification, supplemented by histological data. The latter may be expressed in semiquantitative terms, which helps in the assessment of new therapies.

Biopsy↗
PubMed1996

Delayed-type hypersensitivity skin testing in human immunodeficiency virus-infected pediatric patients.

OBJECTIVE: To evaluate whether pediatric patients infected with human immunodeficiency virus (HIV) can mount appropriate delayed-type hypersensitivity (DTH) skin responses to recall antigens and whether these responses can be correlated with clinical or immunologic parameters. DESIGN: Prospective evaluation of DTH responses in HIV-infected children. Uninfected children born to HIV-infected mothers served as control subjects. Antigens used for yearly DTH testing included Candida albicans (1:100, 1:10); mumps virus; Trichophyton; purified protein derivative of tuberculin; and tetanus toxoid (1:100, 1:10). At the time of each DTH test, patients were staged according to two Centers for Disease Control and Prevention pediatric HIV classification systems, and T-cell subsets were obtained. RESULTS: Twenty-seven HIV-infected patients with a median age at entry of 74.1 (range, 12 to 156) months were followed. Forty-four DTH skin tests in 21 symptom-free HIV-infected patients (PI) and 18 tests in 10 HIV-infected patients with symptoms (P2), as well as 43 DTH skin tests in 18 patients who had either mild or moderate clinical symptoms or immunosuppression and 19 tests in 13 patients with severe symptoms or immunosuppression, were evaluated. Sixteen DTH skin tests were performed in 14 uninfected patients. HIV-infected patients tended to have fewer DTH responses to antigens and of smaller size than did uninfected patients. When controlled for age, few differences in DTH responsiveness were seen between HIV-infected and uninfected patients. Anergy was associated with symptomatic disease, evidence of advanced clinical or immunologic disease, and low CD4+ percentages (p <0.05). CONCLUSIONS: HIV-infected children are able to mount antigen-specific cell-mediated immune responses that are qualitatively similar to those of age-matched control subjects. Loss of DTH responsiveness correlates with both clinical and immunologic evidence of HIV disease progression.

Adolescent↗
PubMed1996

Retrovirus classification and cell interactions.

Retroviruses cause a variety of diseases such as cancer, AIDS, autoimmunity and diseases of central nervous system, bone and joints. Some retroviruses are apparently harmless and some retroviral genomes are even inherited as host mendelian traits. Whereas oncoviruses generally have a low virus load, so that antiviral therapy would not greatly affect disease progression, lentiviruses like HIV have high load and turnover. The cell interactions of retroviruses largely determine their pathogenesis. Finally, retroviruses are being exploited therapeutically as vectors for gene therapy.

Animals↗
PubMed1991

Surface CD4 density remains constant on lymphocytes of HIV-infected patients in the progression of disease.

In an attempt to question the influence of circulating virus, soluble gp120 or CD4 self-reacting antibodies upon results of CD4+ T-cell immunophenotyping in AIDS patients, five anti-CD4 mAb defining several epitopes of the V1 and V2 domains of the CD4 molecule were used to analyse the epitopic density of CD4 on lymphocytes of seropositive patients taken at stages II, III and IV of HIV infection, according to the Centers for Disease Control (CDC, Atlanta) classification. Our results demonstrate that each CD4 epitopic density measured on circulating lymphocytes remains constant at a mean level of 46,000 epitopes per cell whatever the stage of the disease and whatever the serum p25 concentration. These data provide evidence that antibody accessibility to several CD4 epitopes is not altered by putative interactions between CD4 molecules and circulating virus, soluble gp120 or anti-CD4 autoantibodies. If such binding events, as expected, do occur in vivo, they are of too low a magnitude to influence the immunophenotyping. Furthermore, we show that mAb specific for different epitopes in the V1 and V2 domains of the CD4 molecule can be used interchangeably for the biological followup of the CD4+ cell population in blood samples of HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Establishment of a new Epstein-Barr virus nuclear antigen-positive B-cell line, BALL-2, with t(8;14) (q24;q32) chromosome abnormality from B-cell acute lymphoblastic leukemia, L2.

A new Epstein-Barr virus nuclear antigen (EBNA)-positive B-cell line, designated BALL-2, was spontaneously established from the peripheral blood of a 14-year-old boy with an EBNA-negative B-cell acute lymphoblastic leukemia (B-ALL), L2 in the French-American-British classification. The BALL-2 cell line grew in suspension with or without forming clumps of cells. The cultured cells exhibited lymphoid morphology with indented or lobulated nuclei, prominent nucleoli, and relatively abundant cytoplasm. Immunologic and cytogenetic studies showed that the BALL-2 cell line expressed the B-cell phenotype, CpIg+, SmIg+, CD19+, CD20+, CD38-, Ia+, and had chromosome translocation, t(8;14) (q24;q32). The same phenotypic and chromosome markers were present in original leukemia cells. These results indicated that the cell line was derived from the patient's leukemia cells. Unexpectedly, however, BALL-2 cells were positive for EBNA and EB virus DNA. Gene analysis of the BALL-2 cell line showed biallelic rearrangements in the JH locus. One of the JH rearrangement comigrated with a rearranged c-myc gene, indicating the translocation had occurred between JH and c-myc loci. The t(8;14) abnormality is a known chromosome marker of Burkitt lymphoma and L3 type ALL. Our studies revealed that this translocation and myc gene rearrangement can also be found in L2 type B-ALL.

Adolescent↗
PubMed2004

Distribution and prognosis of WHO lymphoma subtypes in Taiwan reveals a low incidence of germinal-center derived tumors.

To assess the distribution of lymphomas in Taiwan according to the WHO (World Health Organization) classification, 175 recently diagnosed cases of malignant lymphomas were studied and the clinicopathologic data were analyzed. B-cell lymphomas accounted for 57.1% of cases, T-cell lymphomas 38.9%, and Hodgkin's lymphoma 4%. Extranodal lymphomas predominated (55.4%). The most common subtype of B-cell lymphoma was diffuse large B-cell lymphoma (33.1%). All tumor types believed to be derived from germinal center (GC) B-cells including follicular lymphoma (4.6%), Burkitt lymphoma (1.7%), Hodgkin lymphoma (4.0%), and GC-like diffuse large B-cell lymphoma (as defined by combined expression of bc1-6 and CD10) were rather uncommon as compared to frequencies seen in series from Western countries. The common T-cell lymphomas included nasal and extranasal NK/T cell lymphoma (7.4%), mycosis fungoides (7.4%), and unspecified peripheral T-cell lymphoma (6.9%). Adult T-cell leukemia/lymphoma was very uncommon and accounts for only 0.6%. The proportional increase in T-cell lymphomas that were unrelated to type I human T-cell lymphotropic virus (HTLV-1) may be linked to differential Epstein-Barr virus (EBV) oncogenesis. The survival data revealed that mantle cell lymphoma, NK/T-cell lymphoma, unspecified peripheral T-cell lymphoma, and subcutaneous panniculitis-like T-cell lymphoma had an aggressive course. Our results confirm the utility of the WHO classification scheme for prognostic stratification and further highlight the distinctive distribution pattern of malignant lymphoma in Taiwan including the higher relative incidence of T cell lymphomas and the rarity of germinal center-derived B-cell tumors.

Follow-Up Studies↗
PubMed2002

An epidemiological study of respiratory syncytial virus associated hospitalizations in Denmark.

Respiratory syncytial virus (RSV) is the most common viral pathogen that causes lower respiratory tract infections in infants. Studies have implicated severe RSV infections early in life as a risk factor for subsequent development of reactive airway disease. We are conducting a study to validate RSV-associated diagnoses in the Danish National Patient Registry, to assess whether the incidence of severe RSV infection is increasing in Denmark, to identify predisposing and protective factors for RSV-associated hospitalization in Denmark, and to examine the association of severe RSV infection with reactive airway disease. The influence of various biological, social and environmental factors on hospitalization for RSV infection will be studied through several population-based registers, including the Danish National Birth Cohort: 'Better health for mothers and children'. The RSV hospitalization cases will be compared with control individuals selected within the same population groups on a case-control or a cohort basis in order to produce estimates of age-adjusted and sex-adjusted relative risks (odds ratio and relative risk) for hospitalization associated with various risk factors. Using register linkage and unique registration of exposures collected through interviews and blood samples from the Danish National Birth Cohort, we will be able to resolve the issues referred to above in a very large sample of Danish children.

Case-Control Studies↗
PubMed2003

Genetic variability of hepatitis A virus.

Knowledge of the molecular biology of hepatitis A virus (HAV) has increased exponentially since its identification. HAV exploits all known mechanisms of genetic variation to ensure survival, including mutation and genetic recombination. HAV has been characterized by the emergence of different genotypes, three human antigenic variants and only one major serotype. This paper reviews the genetic variability and molecular epidemiology of HAV. Its evolutionary mechanisms are described with particular emphasis on genetic recombination and HAV mutation rate. Genotypic classification methods are also discussed.

Amino Acid Sequence↗
PubMed1999

Peripheral T-cell lymphoma other than angioimmunoblastic T-cell lymphoma (AILD), with follicular dendritic cells proliferation and infection of B immunoblasts with Epstein Barr virus.

We describe a case of peripheral T-cell lymphoma, unspecified (REAL) with co-existence of follicular dendritic cell (FDC) proliferation and EB virus-infection. A 55-year-old Japanese man complained of generalized lymphadenopathy and physical examination showed systemic lymphadenopathy, and hepatosplenomegaly. HTLV-1 antibody titers and gamma-globulin level were within normal limits. Histopathologic examination of the right cervical lymph node showed peripheral T-cell lymphoma, unspecified (REAL classification). A diffuse infiltration of lymphoma cells with abundant small venules were found throughout the lymph node. There were few arborizing venules. An irregular meshwork of FDCs was found by immunostaining with DRC-1 and CD21 in the area rich in venules, but not in the area of diffuse lymphoma cell-infiltration. EBER-1 RNA-in situ hybridization showed positive signal on the nuclei of mainly non-neoplastic B immunoblasts. The present case, therefore, was regarded as a rare case of peripheral T-cell lymphoma, unspecified with FDC proliferation and EB virus infection.

B-Lymphocytes↗
PubMed1975

Classification and biological nature of established human hematopoietic cell lines.

Over 200 established human hematopoietic cell lines of normal and malignant origin have been investigated by morphological and functional parameters. Employing morphology as the overriding parameter four types of lines were identified. (1) Lymphoblastoid cell lines, derived from normal and neoplastic hematopoietic tissue, were characterized by the wide morphologic flexibility of individual lymphoblastoid cells, constant association with Epstein-Barr virus (EBV), polyclonal derivation, differentiation for immunoglobulin production (secretion) and their diploids. (2) Lymphoma cell lines. This type of line was established at a high frequency from Burkitt's lymphoma and rarely from other types of lymphoma, but never from patients without malignancy or with non-lymphoma malignancies. Important characteristics were morphologic stereotypia within each line, monoclonal derivation, common but not obligatory association with EBV, variability in the expression of Ig synthesis (no production, or membrane bound Ig, or secretion) and aneuploidy. (3) Myeloma cell lines could only rarely be obtained from patients with myeloma. The basis for classification of these lines is their production of Ig identical to the myeloma protein in vitro. Other important distinguishing features were: plasma cell morphology, absence of EBV and aneuploidy. (4) The leukemia cell line (MOLT 4) was the only line with T-cell characteristics and was easily distinguished from the other types. Important characteristics were a typical surface ultrastructure, absence of EBV and absence of immunoglobulin production, Individual lymphoblastoid lines were in principle identical whereas each line of the other three types had its own characteristic profile. The phenotypic characteristics of the lymphoblastoid lines were very stable during prolonged serial cultivation. Only in a few cases were secondary chromosomal, functional or morphologic alterations noted. We conclude that EBV-carrying lymphoblastoid lines can be obtained from non-neoplastic precursor cells from healthy as well as from diseased individuals. Lymphoma, myeloma and leukemia lines are only obtained from the respective neoplastic tissue but generally at a low frequency. With the exception of Burkitt's lymphoma, malignant hematopoietic tissue and leukemia frequently give rise to established cell lines in vitro of the lymphoblastoid type rather than lines derived from the neoplastic cells;

Antigens, Viral↗