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At least 451 records · Page 25Linked to original sources

PubMed1997

EBV-associated anorectal lymphomas in patients with acquired immune deficiency syndrome.

Primary lymphomas of the gastrointestinal tract represent 9% of all non-Hodgkin lymphomas, and of these only 3% arise in the rectum or anus. In contrast to their rare occurrence in the general population, the incidence of anorectal lymphomas in patients with acquired immune deficiency syndrome (AIDS), particularly homosexual patients, may be as high as 26% as reported in our own series of AIDS-associated lymphomas. To determine the characteristics of this entity, we studied 15 cases of primary anorectal lymphoma in AIDS patients and compared them with four cases of anorectal lymphoma unrelated to AIDS. The cases in our study were also compared with the reports of rectal lymphoma in the medical literature over the past 30 years. In the present series, the AIDS patients were all male with a median age of 34 years, human immunodeficiency virus (HIV)-positive, with homosexuality as the main risk factor. The four non-AIDS patients included a woman and had a median age of 66.5 years. Histologically, the anorectal lymphomas in AIDS patients were all high grade, predominantly immunoblastic, and polymorphous. In the non-AIDS patients, only two of four lymphomas were high grade, including one Burkitt type. All tumors were of B-cell phenotype. In the AIDS-associated anorectal lymphomas, the presence of Epstein-Barr virus (EBV) in a latent form was demonstrated by an abundance of Epstein-Barr-encoded RNA (EBER) in 14 of 15 cases and latent membrane protein (LMP) in four cases. All anorectal lymphomas unrelated to AIDS were negative for EBV. The unusual anorectal location of AIDS-associated lymphomas is explainable by the high incidence of preceding traumatic lesions and chronic infections in the area. As a result, EBV-carrying B cells may be attracted to the field providing the cell population that, under the conditions of immune deficiency, is able to give rise to high-grade lymphomas.

Acquired Immunodeficiency Syndrome↗

PubMed1993

High incidence of Epstein-Barr virus detection in Hodgkin's disease and absence of detection in anaplastic large-cell lymphoma in children.

By in situ hybridization with EBER oligonucleotides and immunohistochemistry with anti-latent membrane protein 1 (LMP1) antibody, we compared the detection rate of Epstein-Barr virus (EBV) in Hodgkin's disease and anaplastic large-cell lymphomas in children. Among the 13 cases of Hodgkin's disease tested, 7 (54%) were found to be EBV associated (EBER transcripts +, LMP1 +). None of the 11 cases of ALC lymphomas was found to contain EBV genomes or gene products. This may indicate that EBV is not a pathogenic agent in anaplastic large-cell lymphomas in children in comparison to Hodgkin's disease.

Adolescent↗

PubMedDate not supplied

Investigations on the dynamics of water in the macrostructural dentine.

The purpose of this study was twofold: (1) to investigate the nature and degree of water loss at 21 degrees C, 60% relative humidity (dehydration) and at 105 degrees C (desiccation), and to relate these findings with (2) the strains produced in the dentine structure during dehydration and rehydration processes. In stage 1, digital moire interferometry (DMI) was used to study the strain distribution pattern during dehydration and rehydration at 21 degrees C. In stage 2, the nature and degree of water loss was determined using gravimetric analysis and nuclear magnetic resonance spectroscopy. DMI showed that dehydration produced strains in the dentine structure after an initial latent period. Gravimetric analysis showed that dentine exhibited an initial rapid water-loss phase followed by a slow and steady water-loss phase. Though the major portion of water loss occurred in the initial 2 h of dehydration (rapid water-loss phase), no obvious strains were produced during this period. Rehydration lead to the major reversal of dehydration-induced water loss and strains in dentine. Heating at 105 degrees C resulted in further substantial loss of water from dentine. These experiments highlighted that the free water in the dentine surface, porosities and tubules are lost rapidly and constitute the major water lost when dehydrated at 21 degrees C.

Absorption↗

PubMed1990

Stimulation of the human immunodeficiency virus type 2 (HIV-2) gene expression by the cytomegalovirus and HIV-2 transactivator gene.

Human immunodeficiency virus (HIV) often causes latent infection. Transactivation by some DNA viruses has been implicated in inducing HIV-1 replication and pathogenesis. The transactivator (IE-2) gene of the human cytomegalovirus (CMV) can enhance HIV-2 as well as HIV-1 gene expression in vitro. This inducer can act in concert with the HIV-2 tat gene and T-cell activation in enhancing gene expression in human CD4+ lymphocytes. While the HIV-2 and HIV-1 tat genes and T-cell activators apparently employ independent modes of action, the CMV transactivator in combination with the HIV-2 tat or T-cell activators may employ a gene activation pathway with some common and some distinct components. Both HIV-2 and CMV transactivators enhance HIV-2 gene expression by transcriptional activation involving transcript initiation as well as elongation, with CMV transactivator affecting elongation more than the initiation. A significant proportion of transcripts appear to terminate prematurely in the absence of transactivators. Deletion mutation analysis of the HIV-2 long terminal repeat (LTR) suggests that the element that responds to CMV transactivation in human CD4+ lymphocytes is either a diffuse one or located downstream of the HIV-2 enhancer element.

CD4-Positive T-Lymphocytes↗

PubMed1998

Lymphoproliferative disorder after liver transplantation.

Lymphoproliferative disorder (LPD) is a well recognized complication of solid organ transplantation. It is associated with Epstein-Barr virus (EBV) infection and is often a fatal complication of immunosuppression. We report a 2.5-year-old boy who developed LPD presenting as small bowel lymphoma after liver transplantation. The patient had intermittent fever after transplantation and reactivation of latent EBV infection was documented by pre- and posttransplant serologic tests. About 5 months after his liver transplantation, the patient had sudden onset of abdominal pain and emergency laparotomy was performed for peritonitis. He proved to have multiple small bowel perforations caused by B cell lymphoma and died of multiple organ failure 9 days after operation, despite aggressive treatment and stopping immunosuppressive agents. We conclude that prevention of overimmunosuppression in pediatric recipients after liver transplantation and early detection and treatment of LPD are important to decrease this often-fatal complication.

Child, Preschool↗

PubMed1998

Differences in Epstein-Barr virus expression between primary and secondary cutaneous angiocentric lymphomas. French Study Group of Cutaneous Lymphomas.

BACKGROUND: Epstein-Barr virus (EBV) has been demonstrated in angiocentric immunoproliferative lesions, suggesting that it could be a causative factor. We investigated for the presence of EBV in 12 primary and 2 secondary cutaneous angiocentric lymphomas (CALs). OBSERVATIONS: In the 2 secondary CALs, strong reactivity for EBV RNAs and latent membrane protein 1 were detected on paraffin-embedded sections. In contrast, 10 of 12 primary CALs were completely negative for EBV RNAs and latent membrane protein 1. In 2 primary CALs, EBV RNAs and latent membrane protein 1 were detected in few tumor cells. In the group of primary CALs, 8 of 12 were still alive at last follow-up, 3 died of systemic lymphoma, and 1 died of another cause, whereas both patients with secondary CALs died of disease within 1 year. CONCLUSION: Differences in the presence of EBV and clinical behavior between primary and secondary CALs suggest that different mechanisms are operative in the pathogenesis of these conditions, and indicate that the 2 groups should be considered separately.

Adult↗

PubMed1980

Evidence for a role of the plasminogen activator--plasmin system in corneal ulceration.

Plasminogen is present in the cornea andcan be activated to plasmin by plasminogen activator. Plasmin is able, in turn, to activate latent collagenase. This system could initiate and perpetuate the collagen degradation of corneal ulceration. This report details evidence for such a system in the cornea. Plasmin has been found to activate latent collagenase from organ cultures of ulcerating rabbit corneas and from fibroblast cultures derived from such corneas. As in the case of activation by trypsin, activation by plasmin results in the conversion of the 40,000 MW latent form to an active species of 23,000 MW. Explants of normal or alkali-burned, ulcerating corneas demonstrated plasminogen-dependent lysis of fibrin clots; frozen sections of such corneas demonstrated that lysis begins in the superficial stroma near the periphery of the cornea. Multiply freeze-thawed ulcerating corneas, but not normal corneas, showed initial lysis, not peripherally but at the ulcer region containing polymorphonuclear leukocytes. The fact that the peripheral lytic pattern existed in corneas that were obtained from eyes prefrozen in liquid nitrogen before excision of the corneas would suggest that plasminogen activator is normally contained in cells in vivo and is not made only in response to tissue injury. There was no correlation between the location of blood vessels or the presence of the corneal endothelium and the plasminogen-dependent lysis. Plasminogen activator from the ulcerating cornea and from fibroblasts was characterized by sodium dodecyl sulfate--gel electrophoresis of its cleavage products of plasminogen. The activator cleaves plasminogen into heavy- and light-chain fragments similar to those produced from plasminogen by urokinase. Plasminogen activator activity was quantitated by a new assay that restricts diffusion of the enzyme to one dimension into a narrow bore tube. The addition of plasminogen daily to cultures of ulcerating corneas resulted in earlier rises of plasminogen activator, collagenase, and collagen degradation fragments in the culture media. Although total plasminogen activator levels were not increased by the addition of plasminogen to culture, levels of both collagenase and solubilized collagen were approximately doubled. It is concluded that the plasminogen activator--plasmin system might play an important role in the destruction of stromal matrix in corneal ulceration.

Animals↗

PubMed2005

In vitro models for the blood-brain barrier.

The aim of the present study was to identify a model for the blood-brain barrier based on the use of a continuous cell line, and to investigate the specificity of this model. A set of test compounds, reflecting different transport mechanisms and different degrees of permeability, as well as different physiochemical properties was selected. In vivo data for transport across the blood-brain barrier of this set of test compounds was generated as part of the study using two different in vivo models. A computational prediction model was also developed, based on 74 proprietary Pharmacia compounds, previously tested in one of the in vivo models. Molsurf descriptors were calculated and 21 descriptors were correlated with log(Brain(conc.)/Plasma(conc.)) using partial least squares projection to latent structures (PLS). However, the correlation between predicted and measured values was found to be rather low and differed between one and two log units for several of the compounds. The test compounds were analyzed in vitro using primary bovine and human brain endothelial cells co-cultured with astrocytes, and also using two different immortalized brain endothelial cell lines, one originating from rat and one from mouse. Cell models using cells not derived from the blood-brain barrier, ECV/C6, MDCK and Caco-2 cell lines, were also used. No linear correlation between in vivo and in vitro permeability was found for any of the in vitro models when all compounds were included in the analysis. The highest r2 values were seen in the bovine brain endothelial cells (r2=0.43) and MDCKwt (r2=0.46) cell models. Higher correlations were seen when only passively transported compounds were included in the analysis, bovine brain endothelial cells (r2=0.74), MDCKwt (r2=0.65) and Caco-2 (r2=0.86). By plotting in vivo Papp values against logDpH7.4 it was possible to classify compounds into four different classes: (1) compounds crossing the blood-brain barrier by passive diffusion, (2) compounds crossing the blood-brain barrier by blood-flow limited passive diffusion, (3) compounds crossing the blood-brain barrier by carrier mediated influx, and (4) compounds being actively excreted from the brain by active efflux. Papp and Pe values obtained using the different in vitro models were also plotted against logDpH7.4 and compared to the plot obtained when in vivo Papp values were used. Several of the in vitro models could distinguish between passively distributed compounds and efflux substrates. Of the cell lines included in the present study, the MDCKmdr-1 cell line gave the best separation of passively and effluxed compounds. Ratios between AUC in brain and AUC in blood were also calculated for six of the compounds and compared to ratios between Pe or Papp for transport in the apical to basolateral and basolateral to apical direction. Again the MDCKmdr-1 cell line gave the best correlation with only one compound (AZT) giving large discrepancy between in vitro and in vivo data. None of the in vitro models could identify compounds known to be substrates for carrier mediated influxed as such, and the results indicate that a tighter in vitro blood-brain barrier model probably is needed in order to facilitate studies on carrier mediated influx. The findings presented also indicate that identification of "batteries" of in vitro tests are likely to be necessary in order to improve in vitro-in vivo correlations and to make it possible to perform acceptable predictions of in vivo brain distributions from in vitro data.

Animals↗

PubMed1993

Detection of Epstein-Barr virus nucleic acid sequences and protein in nodal T-cell lymphomas: relation between latent membrane protein-1 positivity and clinical course.

Forty-six nodal T-cell lymphomas, classified according to the updated Kiel classification, were investigated for the presence of Epstein-Barr virus (EBV) DNA by polymerase chain reaction (PCR), EBER 1 and 2 (EBER 1/2) and latent membrane protein-1 (LMP-1) expression. A combination of RNA in situ hybridization and immunohistochemistry was used to establish the phenotype of the Epstein-Barr virus harbouring cells. In 21 of 45 cases Epstein-Barr virus DNA sequences could be detected with the polymerase chain reaction. In 15 cases (14 of 21 EBV PCR positive cases), EBER 1/2 positive cells could be demonstrated. As judged by morphology, EBER 1/2 expression was found in nonneoplastic and neoplastic lymphoid cells. Double staining revealed that more than 80% of the EBER 1/2 harbouring cells, lacked B-, T- or histiocytic markers, suggesting down regulation of T- and B-cell markers by Epstein-Barr virus. In eight of 15 cases some EBER 1/2 positive T-cells (CD3, CD45RO, CD43) morphologically resembling tumour cells were found. In nine of 14 cases tested EBER 1/2 positive non-neoplastic B-cells (CD20) were seen. Based on in situ hybridization results, four patterns of EBER 1/2 positive cells were found, i.e. single cells (< 1 per medium power field (mpf), n = 3), scattered (1-25/mpf, n = 4), clustered (26-100/mpf, n = 5) and diffuse (> 100/mpf, n = 3). In eight of 15 cases a clustered or diffuse pattern of EBER 1/2 positive cells was found and these lymphomas were therefore considered to be strongly associated with Epstein-Barr virus. In these lymphomas LMP-1 expression was found to be associated with an aggressive clinical course and hepatosplenomegaly.

Herpesvirus 4, Human↗

PubMed1985

Localization of the coding region for an Epstein-Barr virus early antigen and inducible expression of this 60-kilodalton nuclear protein in transfected fibroblast cell lines.

Expression of a component of the Epstein-Barr virus early antigen (EA) complex has been studied in fibroblast cells transfected with both wild-type and P3HR-1 defective DNA fragments covering the BamHI-M-S region of the Epstein-Barr virus genome. Baby hamster kidney (BHK) cells transfected with the BglII-J fragment and stained with human serum that was positive for the diffuse component of EA [EA(D)] in an indirect immunofluorescence assay exhibited positive nuclear staining in 5% of the cell population. Cleavage of BglII-J before transfection with the restriction enzyme BglII, StuI, HindIII, or PvuII did not affect EA expression, whereas prior cleavage with BamHI or EcoRI reduced or eliminated synthesis of EA. These observations were confirmed by using individual cloned subfragments. A Bal 31 deletion clone (pTS1) in which the HindIII and StuI sites were eliminated retained activity, whereas a clone (pTS5) in which the deletion extended closer to the EcoRI site had greatly reduced activity. Transfection of the individual BamHI-M or BamHI-S fragments, which span BglII-J, also resulted in little or no EA expression. The 2.1-kilobase biologically active region defined by these experiments corresponds precisely to the BMLF1 open reading frame. Immunoblot analyses of BHK cells transfected with either P3HR-1 defective DNA clones or the BglII-J wild-type fragment identified the product of this EA(D) coding region as a family of polypeptides consisting of a major 60-kilodalton product and minor 45- and 50-kilodalton species. In latently Epstein-Barr virus-infected lymphocytes these early antigens are not expressed, but can be induced by treatment of the cultures with sodium butyrate or phorbol esters. Using the BglII-J and pTS6 clones that were positive in transient assays, we also established Neor coselected BHK and Vero cell lines which showed similar regulated expression of the 60-kilodalton EA(D) protein. In these cell lines constitutive expression of EA(D) was limited (0.1% positive by indirect immunofluorescence and undetectable by immunoblot analysis). However, expression of EA(D) could be induced by treatment with sodium butyrate. In the induced cultures, up to 30% of the cells were EA(D) positive by immunofluorescence, and there was a concomitant appearance of the 60-kilodalton EA(D) polypeptide.

Animals↗

PubMed2002

Plasmablastic lymphoma: an HIV-associated entity with primary oral manifestations.

Plasmablastic lymphoma is a relatively new entity that is considered to be a diffuse large B-cell lymphoma with an unique immunophenotype and a predilection for the oral cavity. We present a 50 year-old HIV-positive, bisexual, white male with a CD4 count 300/mm(3) and a viral HIV-RNA polymerase chain reaction (PCR) load of 237 copies/ml, who developed a painful, purple-red mass in the edentulous area of the maxillary right first molar. Erythematous gingival enlargements of the interdental papillae were seen in three of the dental quadrants. In addition, the patient was being managed with antiretroviral therapy and liposomal doxorubicin for recurrent cutaneous Kaposi's sarcoma (KS). Although oral KS was suspected, the gingival lesions were biopsied because they were refractory to chemotherapy and a lymphoma could not be excluded. Histopathologic examination revealed a lymphoid malignant neoplasm, consistent with a plasmablastic lymphoma. Immunoreactivity with vs38c, CD79a, kappa light chain, and IgG was readily identified in tumor cells; while only focal cells expressed CD20 and LCA (CD45RB). CD56, CD3, lambda light chain, and EMA were non-reactive. EBV was detected in the tumor by Southern hybridization, PCR amplification, in situ hybridization for EBER-1 DNA, and immunohistochemistry for latent membrane protein-1. The same tumor was negative for HHV-8 by PCR. Recognition of plasmablastic lymphoma is important, because it represents an HIV-associated malignancy that predominantly involves the oral cavity, may mimic KS and has a poor prognosis.

Antiretroviral Therapy, Highly Active↗

PubMed1991

Transformation by the oncogenic latent membrane protein correlates with its rapid turnover, membrane localization, and cytoskeletal association.

The latent membrane protein (LMP) of Epstein-Barr virus (EBV) has a short half-life (V. R. Baichwal and B. Sugden, J. Virol, 61:866-875, 1987; K.P. Mann and D. Thorley-Lawson, J. Virol, 61:2100-2108, 1987), is localized in patches in the membrane (D. Liebowitz, D. Wang, and E, Kieff, J. Virol, 58:233-237, 1986), and associates with the cytoskeleton in EBV-immortalized B lymphocytes (D. Liebowitz, R. Kopan, E. Fuchs, J. Sample, and E. Kieff, Mol. Cell. Biol. 7:2299-2308, 1987; K. P. Mann and D. Thorley-Lawson, J. Virol. 61:2100-2108, 1987). Deletion mutants of LMP that are either positive or negative in the induction both of anchorage-independent growth of BALB/c 3T3 cells (V. R. Baichwal and B. Sugden, Oncogene 4:67-74, 1989) and of cytotoxicity in a variety of cells (W. Hammerschmidt, B. Sugden, and V. R. Baichwal, J. Virol. 63:2469-2475, 1989) have been studied to identify the biochemical properties of this protein that correlate with its effects on cell growth. Mutant LMP proteins that are metabolically stable, do not associate with the cytoskeleton, and exhibit a diffuse plasma membrane localization also do not induce anchorage-independent growth in rodent cells or cytotoxicity in B lymphoblastoid cells. In contrast, a mutant of LMP that is functionally identical to the wild-type protein has a half-life, membrane localization, and cytoskeletal association similar or identical to those of LMP. These results are consistent with the hypothesis that LMP's rapid turnover, association with the cytoskeleton, and patching in the membrane are required for it to affect cell growth.

Animals↗

PubMed2005

MMP-2 expression in uveal melanoma: differential activation status dictated by the cellular environment.

PURPOSE: MMPs are recognized to play a major role in tumor progression and metastasis of many forms of cancers. The purpose of this study was to compare the expression and activity of MMP-2 in uveal melanoma cell lines grown either in vitro on plastic culture plates or in vivo as tumors produced in chick embryos. METHODS: The chick chorioallantoic membrane (CAM) model was used to evaluate the tumorigenic potential of uveal melanoma cell lines derived either from the primary uveal melanoma tumor isolated from three different patients (cell lines SP6.5, SP8.0, and TP31) or from a metastatic lesion derived from the liver of a patient diagnosed with uveal melanoma (cell line H79). The presence of MMP-2 in the vicinity of the tumor cells was determined by immunofluorescence analyses. Gelatin zymography was used for the detection of latent and activated forms of MMP-2 in uveal melanoma cell lines when grown in vitro on plastic, or in the solid tumors these cell lines produced in vivo on the CAM of the chick embryo. The gelatinase activity was quantified by densitometric analyses and the active/(active+pro-form) ratio was calculated as the MMP-2 activation ratio. Western blot analyses were performed to confirm the zymographic profile. RESULTS: Only the inactive form of MMP-2 was expressed and secreted in vitro by all uveal melanoma cell lines, higher levels being found for the liver-derived H79 cell line whereas SP8.0 only expressed MMP-2 to a very low level. On the other hand, all solid tumors produced in the CAM from these cell lines expressed and secreted, although to varying levels (SP6.5 and SP8.0, TP31 and H79), primarily the active form of MMP-2. Gelatinolytic activities of active MMP-2 were significantly higher in uveal melanoma tissues than in the non-neoplastic CAM, as revealed by the measurement of the activation ratio. The immunolocalization of MMP-2 revealed that all cell lines were MMP-2-positive although a reduced and more diffuse staining was observed for H79 and SP6.5 than in SP8.0 and TP31 cells. CONCLUSIONS: These results suggest the activation of proMMP-2 as an important event in the process of uveal melanoma progression. An elevated active to inactive MMP-2 ratio in the tumor environment of uveal melanoma suggests that a potential MMP-2 activity could be related to the progression of this type of cancer.

Aged↗

PubMed1988

Increased mortality of diabetics after acute myocardial infarction attributed to diffusely impaired left ventricular performance as assessed by echocardiography.

Five hundred and forty-eight patients who sustained their first acute myocardial infarction (AMI) were admitted to the coronary care unit (CCU). Ninety-eight of them were known diabetics. The diabetic patients were younger, 50 +/- 12 vs. 64 +/- 18 years of age (p less than 0.05), and the proportion of females in their group was higher than in the nondiabetics, 44% vs. 33.4% (p less than 0.05). The in hospital mortality rate was 30% for diabetics and 16% for nondiabetics (p less than 0.001). Diabetics had a higher percentage of mortality caused by left ventricular failure (LVF) (p less than 0.025) and a tendency for more frequent complete A-V block (p less than 0.01) compared to nondiabetics. Obesity and a positive family history for coronary heart disease were more prevalent in the diabetic group (both p less than 0.01). The echocardiographic assessment of left ventricular function, performed in 125 consecutively admitted patients (25 diabetics and 100 nondiabetics) on the 3rd-5th post-infarct day, showed that the indices of myocardial contractility, that is, E point septal separation (EPSS), ejection fraction (EF) and fractional shortening (FS) were far more impaired in diabetics than in nondiabetics (p less than 0.01, p less than 0.005, p less than 0.005, respectively). No significant difference was found in the prevalence of dyskinetic, akinetic and hypokinetic segments between the two categories of patients, suggesting no difference in the amount of myocardial mass affected by the AMI. Our results indicate that the increased incidence of LVF developed in diabetics after an AMI compared to nondiabetics may be caused by other factors, probably some form of latent diabetic cardiomyopathy as a result of either small vessel disease or metabolic disorder.

Aged↗

PubMed1997

Pyothorax-associated lymphoma: description of the first two cases detected in Italy.

BACKGROUND: Pyothorax-associated lymphoma (PAL) is a rare, but distinct, clinico-pathologic entity which occurs most often in Japanese people; to the best of our knowledge, only six cases of it have been reported in Western countries. The tumour develops several decades following artificial pneumothorax or chronic pleuritis due to tuberculous infection, produces pleural effusion associated with extensive local lymphomatous infiltrates, and is sustained by a polymorphic large B-cell clonal proliferation showing EBV integration in the genoma of the neoplastic cells. PATIENTS AND METHODS: Herein we describe two cases of PAL observed in Italian patients, both extensively studied on the clinical, pathological, phenotypic, virological, and molecular levels. RESULTS: The two cases occurred, respectively, 45 and 50 years after therapeutic pneumothorax because of tuberculous pleuritis and were characterized by a pleural mass extending to the thoracic wall, which on histological examination were seen to consist of large elements with immunoblastic morphology. Immunohistochemistry show monotypic restriction of Ig light chains, as well as the expression of CD45, B-cell markers (CD20, CD79a, CD45RA), bcl-2 oncogene product, EBNA-2 and, partially, LMP-1. The ratio of cycling cells was extremely high as was the number of mitotic figures. In situ hybridization displayed the presence in the neoplastic cells of the EBV-related small RNAs EBER 1 and 2, which in turn, along with the positivity for EBNA-2 and LMP-1, further strengthened the close relationships between PAL and latent viral infection. Molecular studies revealed, on one hand, clonal rearrangement of the Ig heavy chain J region genes, and on the other, negativity for HHV8 in one case and positivity in the other. CONCLUSIONS: These cases of PAL are the first to be documented in Italy; they serve to direct attention to the fact that this condition is not confined to Japanese people, and that its occurrence in Western countries might be underestimated.

Aged↗

PubMed1979

Immunochemical characterization of Epstein-Barr virus-associated early and late antigens in n-butyrate-treated P3HR-1 cells.

Sodium butyrate induces the Epstein-Barr virus cycle in latently infected P3HR-1 cells with a high efficiency. This fact was utilized for the metabolic labeling of the Epstein-Barr virus antigens. Nonproducer Raji cells, lacking both early antigen and viral capsid antigen, were used as controls. Immunoprecipitation patterns were compared with 13 anti-Epstein-Barr virus (viral capsid antigen) - positive and 3 negative sera. Sixteen polypeptides were identified as being associated with the lytic Epstein-Barr virus cycle. Their molecular weights ranged from 31,000 (31K) to 275K on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two polypeptides, 158K and 165K, could be classified as late viral products on the basis of their sensitivity to cytosine arabinoside. Six of the polypeptides, i.e., 90K, 95K, 134K, 165K, 236K, and 275K, were detected by [(3)H]glucosamine labeling. Among the early, cytosine arabinoside-insensitive polypeptides detected by [(35)S]methionine labeling, a 152K component appears to be a major constituent of early antigen. This polypeptide was precipitated by all anti-Epstein-Barr virus-positive sera tested. As a rule, together with the 103K and 134K polypeptides, the 152K component is precipitated by anti-early antigen, R (restricted) antibodies. In addition, anti-early antigen D (diffuse) antibodies precipitate 31K, 51K, 65K, and 90K components.

Antigens, Viral↗

PubMed2003

Molecular histogenesis of posttransplantation lymphoproliferative disorders.

Posttransplantation lymphoproliferative disorders (PTLDs) represent a serious complication of solid organ transplantation. This study assessed the molecular histogenesis of 52 B-cell monoclonal PTLDs, including 12 polymorphic PTLDs (P-PTLDs), 36 diffuse large B-cell lymphomas (DLBCLs), and 4 Burkitt/Burkitt-like lymphomas (BL/BLLs). Somatic hypermutation (SHM) of immunoglobulin variable (IgV) genes documented that most monoclonal B-cell PTLDs (75% P-PTLDs, 91.3% DLBCLs, 100% BL/BLLs) derive from germinal center (GC)-experienced B cells. B-cell lymphoma 6 (BCL6) mutations occurred in 25% P-PTLDs, 60.6% DLBCLs, and 75.0% BL/BLLs. A first histogenetic category of PTLDs (31.2% DLBCLs) express the BCL6+/multiple myeloma oncogene-1 protein (MUM1-/+)/CD138- profile and mimic B cells experiencing the GC reaction, as also suggested by ongoing SHM in a fraction of these cases. A second subset of PTLDs (66.7% P-PTLDs and 31.2% DLBCLs) display the BCL6-/MUM1+/CD138- phenotype and mimic B cells that have concluded the GC reaction. A third histogenetic category of PTLDs (25.0% P-PTLDs and 31.2% DLBCLs) shows the BCL6-/MUM1+/CD138+ profile, consistent with preterminally differentiated post-GC B cells. Crippling mutations of IgV heavy chain (IgVH) and/or IgV light chain (IgVL) genes, leading to sterile rearrangements and normally preventing cell survival, occur in 4 DLBCLs and 1 BL/BLL that may have been rescued from apoptosis through expression of Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1). Overall, the histogenetic diversity of monoclonal B-cell PTLDs may help define biologically homogeneous categories of the disease.

Adolescent↗

PubMed1991

Epstein-Barr virus DNA and latent gene products in Ki-1 (CD30)-positive anaplastic large cell lymphomas.

Epstein-Barr virus (EBV)-specific DNA sequences were detected by polymerase chain reaction analysis in 15 of 47 (32%) DNA extracts prepared from CD30-positive (Ki-1 antigen-positive) anaplastic large cell (ALC) lymphomas. EBV-encoded RNA (EBER) transcripts could be detected by in situ hybridization in the tumor cells of 9 of 11 EBV DNA-positive cases. Twenty-eight cases were examined by immunohistology on cryostat sections for the presence of the EBV-encoded latent membrane protein (LMP), the nuclear antigen 2 (EBNA2), the BZLF1 transactivator protein, and the late viral glycoprotein gp350/250. A distinct LMP-specific membrane and cytoplasmic staining was detected exclusively in lymphoma cells of five cases (18%); two of these cases additionally expressed EBNA2. BZLF1 protein and gp350/250 immunoreactivity was absent in all instances. All LMP-positive cases contained EBV DNA and EBER sequences. The pattern of EBV latent protein expression in ALC lymphomas showed heterogeneity with respect to EBNA2 expression: LMP-positive/EBNA2-negative cases displayed a pattern previously described for undifferentiated nasopharyngeal carcinomas and Hodgkin's disease, whereas LMP-positive and EBNA2-positive cases showed parallels to lymphoblastoid cell lines. Because the LMP gene has transforming potential, our findings support the concept of a pathoetiologic role for EBV in a proportion of CD30-positive ALC lymphomas.

Adult↗