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An endoscopic follow-up study of the development of diffuse antral vascular ectasia.

No endoscopic follow-up studies are available on the development of diffuse antral vascular ectasia (DAVE). We present here a ten-year follow-up study from discrete initial lesions to the full picture of DAVE. In a 72-year-old female patient with liver cirrhosis, the earliest findings of DAVE were several red spots, with or without a white halo, in the distal antrum. During follow-up, the spots increased in number, coalesced, and extended to the proximal antrum. Three years after the initial findings, latent hemorrhage occurred at a time when confluent lesions were formed. One year later, diffuse distribution of the antral lesions was observed, which led to the diagnosis of DAVE and developed to the full picture within three more years. Two years later, the patient presented with hematemesis, which confirmed the diagnosis of DAVE clinically. Treatment consisted of monopolar electrocoagulation, leading to a stable hemoglobin value for one year. This case study provides some substantial clues to the early detection and treatment of DAVE.

Aged↗

Immunofluorescence microscopy and flow cytometry characterization of chemical induction of latent Epstein-Barr virus.

The effects of chemical induction of latent Epstein-Barr virus (EBV) with 12-O-tetradecanoyl phorbol-13-acetate (TPA) and n-butyrate on cell viability and induction of latent EBV in Raji and X50-7 B lymphocytes, indicated by expression of the diffuse component of the EBV early antigen (EA-D), were measured by visual immunofluorescence microscopy (of both viable and nonviable cells) and fluorescence-activated cell sorter (FACS) flow cytometry (of viable cells only). Cell viability at 4 days decreased moderately for treated Raji cells (9 to 37%, compared to 55 to 69% for untreated cells) and markedly for X50-7 cells (1-32% compared to 35-44% in untreated cells). The highest EA-D levels in viable cells occurred in Raji cells treated with both TPA and n-butyrate and untreated X50-7 cells. TPA and n-butyrate acted synergistically to induce latent EBV, resulting in increased levels of EA-D production in Raji cells and cell death in X50-7 cells. Methodological differences including the ability to detect antigen in only viable cells by FACS flow cytometry accounted for the higher levels of EA-D observed by FACS analysis compared to the levels observed by immunofluorescence microscopy. FACS analysis may be more objective and reproducible than immunofluorescence microscopy for the detection of EBV induction and also permits viral protein expression to be distinguished in the subpopulation of viable cells.

Antigens, Viral↗

Changes in the carbon monoxide diffusing capacity of the lung in ulcerative colitis.

The aim of this study was to investigate lung function in patients with ulcerative colitis and to assess the incidence of latent pulmonary involvement in subjects with active and inactive disease. After full colonscopic assessment with multiple mucosal biopsy, the clinical disease activity of each patient was quantified, using the simple index of Harvey and Bradshaw. The patients were divided into 2 equal groups: subjects with active disease (group 1; n=16); and those with inactive disease (group 2; n=16). Global spirometry was then performed. A latent pulmonary involvement was found in 17 of 32 patients (53%), the incidence was higher in the group 1 patients (81%). The majority of patients presented a reduction in the carbon monoxide diffusing capacity of the lungs (DL,CO). The mean DL,CO value was 73.87+/-14.87 in group 1 and 87.31+/-11.23 in group 2. The DL,CO and KCO reduction correlated significantly with intestinal histopathological grading in the group of patients with active disease (r=0.87, p<0.001; r=0.603, p=0.015). To conclude, a high incidence of pulmonary function abnormalities were identified, despite the lack of radiological alterations (High Resolution Computed Tomography) and pulmonary symptoms, in ulcerative colitis patients. These alterations were more common in patients with active disease. The strong correlation between DL,CO values and histopathological grading suggests that this test may reflect bowel disease activity.

Adult↗

Simultaneous progressive multifocal leukoencephalopathy, Epstein-Barr virus (EBV) latent infection and cerebral parenchymal infiltration during chronic lymphocytic leukemia.

We report a non-HIV patient who had B chronic lymphocytic leukemia (CLL) with progressive multifocal leukoencephalopathy (PML) and diffuse cerebral leukemic parenchymal infiltration in the presence of JC virus and Epstein-Barr virus (EBV) cerebral co-infection. Multiple subcortical hypodensities lining the cortico-subcortical junction were present within the white matter on computerized tomography (CT) scan, with large areas of high signal intensity on T2-weighted sequences on magnetic resonance imaging (MRI). JCV DNA was identified in peripheral blood nuclear cells and cerebrospinal fluid polymerase chain reaction (PCR) DNA/DNA hybridization plus Southern blot analysis. Frontal stereotactic biopsy confirmed the diagnosis of PML by immunocytochemistry, in situ hybridization (ISH) with JC Enzo probe and electron microscopy. Leukemic B cells with the same phenotype as leukemic blood cells were disseminated in the demyelinated areas. They were labeled by anti-latent membrane protein and by BamHl W EBV probe after ISH. Adhesion and activation molecules were positive for CD23. Autopsy showed diffuse visceral leukemic infiltration without acutization. EBV-transformed B lymphocytes would favour JCV penetration and/or intracerebral reactivation of previously latent JCV infection with further development of simultaneous PML and cerebral CLL infiltration in an immunosuppressed patient.

B-Lymphocytes↗

Angioimmunoblastic T-cell lymphoma with supervening Epstein-Barr virus-associated large B-cell lymphoma.

Patients with angioimmunoblastic T-cell lymphoma can have profound immune dysfunction and immunodeficiency. Epstein-Barr virus-driven B-cell lymphoid proliferation can occur in angioimmunoblastic T-cell lymphoma, as in other immunodeficiency states. However, few cases of Epstein-Barr virus-positive B-cell lymphoma arising in patients with preexisting angioimmunoblastic T-cell lymphoma have been reported. We report a case of angioimmunoblastic T-cell lymphoma in which diffuse large B-cell lymphoma developed 56 months after the diagnosis of angioimmunoblastic T-cell lymphoma. The patient survived for 9 years after the initial diagnosis of angioimmunoblastic T-cell lymphoma, and molecular studies performed on multiple biopsy specimens during this period revealed the dynamic nature of clonal lymphoid expansion. Epstein-Barr virus latent membrane protein 1 and Epstein-Barr virus-encoded RNA were detected in the diffuse large B-cell lymphoma, suggesting that Epstein-Barr virus may have played a role in the pathogenesis of the diffuse large B-cell lymphoma.

Aged↗

Predictive value of laminin-5 and membrane type 1-matrix metalloproteinase expression for cervical lymph node metastasis in T1 and T2 squamous cell carcinomas of the tongue and floor of the mouth.

BACKGROUND: Laminin-5 (Ln-5) cleaved by membrane type 1-matrix metalloproteinase (MT1-MMP) enhances the migration of tumor cells. The purpose of this study was to determine whether or not enhanced expression of both Ln-5 and MT1-MMP was associated with lymph node metastasis in patients with T1 and T2 squamous cell carcinoma (SCC) of the tongue and floor of the mouth. METHODS: By use of biopsy specimens of primary tumors from 57 patients, intratumoral expression of Ln-5 and MT1-MMP was evaluated immunohistochemically and its association with node metastasis analyzed. RESULTS: The tumors were categorized into three groups: Ln-5 focal type/MT1-MMP (-) (group I, n = 14), Ln-5 focal type/ MT1-MMP (+) and Ln-5 diffuse type/MT1-MMP (-) (group II, n = 16), and Ln-5 diffuse type/MT1-MMP (+) (group III, n = 27). The incidence of node metastasis (initial and latent metastases) was two of 14 (14.3%), five of 16 (31.3%), and 15 of 27 (55.6%) in groups I, II, and III, respectively. Multivariate analysis identified tumor thickness (odds ratio, 4.751; p = .0152) and Ln-5/ MT1-MMP expression (odds ratio, 3.795, p = .0304) as independent factors of node metastasis. Moreover, in 35 patients with N0 disease, Ln-5/MT1-MMP expression was the only parameter associated with latent node metastasis (odds ratio, 12.800, p = .0247). CONCLUSION: These results suggest that immunohistochemical evaluation of Ln-5 and MT1-MMP expression is useful for identifying patients with T1 and T2 SCC of the tongue and floor of the mouth who should be treated with elective neck dissection.

Adult↗

Association of collagenase and tissue inhibitor of metalloproteinases (TIMP) with hypertrophic cell enlargement in the growth plate.

In the transition from proliferating to hypertrophic cell zones in the growth plate, there is an increased in chondrocyte cell volume and a corresponding decrease in collagen content to allow for cell enlargement. To substantiate our hypothesis that collagenase is responsible for these changes, growth plates from rats treated with bisphosphonate (HEBP) were compared histologically and biochemically with growth plates from normal and vitamin D and phosphate deficient (-VDP) rats. HEBP-treated rats developed an expanded hypertrophic cell zone (HCZ) characterized by the presence of two distinct populations of hypertrophic cells. The proximal hypertrophic cells were only 2-fold enlarged compared to the proliferating cells, whereas 1/6 of the distal hypertrophic cells were enlarged almost 5-fold and appeared morphologically identical with hypertrophic cells from normal and -VDP rats. The HEBP growth plates were divided into cross-sectional thirds and analyzed for active and latent collagenase. The juxta-metaphyseal (lower 1/3) cartilage contained 100% of the fully enlarged hypertrophic cells and appeared identical to those found in normal and -VDP growth plates, along with 81% of the active and 77% of the total collagenase. Collagenase and tissue inhibitor of metalloproteinases (TIMP) were measured in extracts of similarly divided tissues. The presence of true collagenas was confirmed by using [3H]-telopeptide-free collagen. TIMP levels were inversely related to the presence of active collagenase and cellular hypertrophy. Substantial levels of latent collagenase were found in the extracellular fluid at sites of active collagenolysis, but not in the fluid phase surrounding the 2-fold enlarged hypertrophic cells. It is postulated that increased amounts of active collagenase and insufficient levels of TIMP may account for the reduced collagen content seen in the lower HCZ of both -VDP and HEBP rickets. Unlike active collagenase, which remains localized by binding to collagen, latent enzyme is probably restricted in its mobility throughout the extracellular space by diffusion, itself, or the interstices of the extracellular matrix.

Animals↗

[Antibiotic resistance in Staphylococcus aureus mastitis in sheep, sheep milk and its products].

A study of current resistance to antibiotics was conducted in 500 strains of Staphylococcus aureus isolated from ewes with clinical and latent mastitis, from sheep milk and products made from it (sheep lumpy cheese, bryndza cheese). A diffusion disk method was used to assay 14 kinds of antibiotics (AMP, BAC, CEF, ERY, GEN, CMP, KAN, LIN, OXA, PEN, RIF, SPI, VAN, TET) and one chemotherapeutic drug (COT). The highest resistance was observed in the cases of clinical mastitis (from 8% and 10% in COT and KAN to 68% and 69% in PEN and TET). Resistance significantly decreased in 13 kinds of antibiotics in the group of cases with latent mastitis (from 3% in SPI to 30% in PEN), it increased in KAN (13%) and COT (12%) only. Resistance also decreased in bulk samples of sheep milk; it was the highest in PEN (27%) and AMP (17%) and the lowest in CEF, RIF and SPI (5%). Sheep lumpy cheese and bryndza cheese are mostly made from unpasteurized milk. Resistance continued to decrease even in these dairy products. It ranged from 2% in CEF to 16% in OXA in sheep lumpy sugar, while it varied from 0% in SPI to 14% in TET in bryndza cheese. The results demonstrate that sheep milk and products made from it are not any important sources of antibiotic resistance of S. aureus in Central Slovakia.

Animals↗

Penicillin epileptogenesis in the rat: diffusion and the differential laminar sensitivity of the cortex cerebri.

When penicillin is applied electrophoretically from a fluid-filled microelectrode into the substance of the somatosensory cortex of the rat under urethane anaesthesia, the latent period for production of interictal epileptic spikes is least when the electrode lies 0.7 mm below the cortical surface. With low electrophoretic currents of --50 to 100 nA the increase in latent period as the tip of the electrode is placed further and further away from this level can be quantitatively accounted for by the time taken for penicillin to diffuse and to reach a threshold concentration throughout a critical mass of tissue at the 0.7 mm level. With these low currents, the generators of the interictal spikes are confined to a band of cortex centred at the 0.7 mm level. This is true even when the penicillin is applied away from the sensitive layer; in this circumstance the duration of electrophoresis needed to evoke interictal spikes is greater but when they do eventually appear the spikes are generated at the 0.7 mm layer. Histologically, the sensitive layer has been identified as the deep part of layer III. So far as the generation of interictal spikes is concerned, there is no evidence that, with low electrophoretic currents, penicillin has effects other than at the deep part of layer III; all the available evidence indicates that the penicillin has to diffuse to this layer and produces its effects there.

Animals↗

[Epstein-Barr virus associated Richter's syndrome accompanied by interstitial pneumonia].

A 65-year-old man who had an 8-year history of chronic lymphocytic leukemia was admitted to our hospital on February 19, 1998 because of high fever, dry cough, and weight loss. Laboratory data on admission included serum lactate dehydrogenase at 980 IU/l, CRP at 21.8 mg/dl, and soluble interleukin-2 receptor at 7,280 U/ml. The results of serological tests for Epstein-Barr virus (EBV) antibodies were as follows: EBV capsid antigen IgG 1:2560, EBV early antigen IgG 1:640, and EBV nuclear antigens 1:20. Computed tomography revealed diffuse interstitial pneumonia in both lungs, hepatosplenomegaly with multiple nodules, and enlarged intra-abdominal lymph nodes. In addition, Gallium-67 scintigraphy demonstrated abnormal accumulations. Although the patient initially responded well to combination chemotherapy, he eventually deteriorated and died on November 2, 1988, despite salvage chemotherapy. Postmortem needle biopsy specimens from the liver and spleen revealed diffuse proliferation of polymorphic large lymphoma cells. The lymphoma cells were positive for L-26, latent membrane protein 1, and EBV nuclear antigen, but negative for UCHL-1 and CD3, 5, 10, and 30. In situ hybridization procedures disclosed the presence of EBV-encoded small RNA in lymphoma cells. These findings suggested the possibility of association with EBV infection in some cases of Richter's syndrome.

Aged↗

A tractable deterministic model with realistic latent period for an epidemic in a linear habitat.

This paper describes a model for the spatial spread of an epidemic in which the latent period has a Gamma distribution with arbitrary mean and variance while the infected and uninfected may have different diffusion coefficients. Using a variant of the "linear chain trick" we derive a simple algorithm for the propagation speed of the infection front. By way of verification, we show that, with suitably matched parameters, the algorithm agrees closely with speeds obtained numerically from the corresponding model in which the latent period is a constant.

Algorithms↗

Brain lymphomas of immunocompetent and immunocompromised patients: study of the association with Epstein-Barr virus.

The Epstein-Barr virus (EBV) has been described in association with lymphomas of the central nervous system. To test if the association between EBV and central nervous system lymphomas was limited to patients with immunosuppression or whether the association also held for patients who were immunocompetent and to determine the true prevalence of any association, we studied 37 formalin-fixed, paraffin-embedded cases of central nervous system lymphomas occurring in immunocompromised and immunocompetent patients. EBV DNA-RNA in situ hybridization was performed using a 30-base biotinylated antisense oligonucleotide complementary to the EBER1 gene of EBV. Immunohistochemistry was also performed, using a monoclonal antibody to the latent membrane protein of EBV. The most common histologic subtypes of lymphoma were high grade immunoblastic (57%), diffuse large cell (22%), and small, noncleaved, non-Burkitt's (11%). Eighty-six percent of all tumors in our series were of B-cell lineage, as confirmed by CD20 expression, but only 37% of the primary tumors showed restricted CD20 expression. EBV RNA was identified in all or virtually all of the malignant lymphoid cells in 11 of the 37 cases (30%), including 10 primary brain lymphomas and one metastasis from systemic disease. Latent membrane protein expression was identified in 64% of the EBER1-positive cases. All 10 patients who had a history of immunosuppression had tumors that expressed EBV RNA. We confirm the strong association of EBV with brain lymphomas occurring in immunocompromised patients, whether due to AIDS or to the immunosuppression associated with organ transplantation. Our findings also demonstrate a low rate of EBV-positivity in immunocompetent patients.

Adolescent↗

An indolent type of Epstein-Barr virus-associated T-cell-rich B-cell lymphoma of the skin: report of a case.

A 74-year-old Japanese man presented with systemic lymphadenopathy, hepatosplenomegaly, and erythroderma in December 1991. A characteristic pattern of anti-EBV antibodies was suggestive of latent EBV infection. A skin tumor biopsied in April 1993 contained biclonal EBV genomes diffusely in the infiltrate of polyclonal T cells and monoclonal B cells. The clinical course was rather mild in contrast to that of classical EBV-associated disorders. Our case was considered a rare indolent type of EBV-associated T-cell-rich B-cell lymphoma of the skin.

Aged↗

The influence of NaCl on leaf water relations and the proportions of K, Na, Ca, Mg, and Cl in epidermal cells of Fraxinus excelsior L.

The influence of NaCl on leaf water relations was investigated in 3-4-year-old, potted Fraxinus excelsior L. trees. Until midsummer, the application of NaCl to the soil resulted in increased leaf water potentials (Psi) and stomatal diffusive resistances (r(s)). The improved water status seems to be due to a latent injury rather than to an adaptive response of the plant because, despite the initial increases in Psi and r(s), leaf necrosis developed in midsummer. Altered hydraulic resistances were detected at the time the leaves became necrotic. X-ray analysis of frozen, hydrated leaf tissue from NaCl-treated trees showed substantial increases in Ca(2+) and Mg(2+) content in the epidermal cells. These changes in elemental composition of the leaves from NaCl-treated plants may be associated with malfunction of the stomatal apparatus.

Journal Article↗

Genetic predisposition to pre-B lymphomas in SL/Kh strain mice.

Genetic predisposition of SL/Kh mice to spontaneous pre-B lymphomas was investigated in crosses between SL/Kh and NFS/N, another inbred strain of mice lacking endogenous ecotropic provirus and spontaneous lymphoma. (SL/Kh x NFS/N) F1 hybrids developed lymphomas similar to those in SL/Kh but at a lower frequency and with a longer latent period. Of 83 backcross mice to NFS/N, 22 developed hemopoietic tumors: 8 were diffuse lymphoblastic lymphomas; 2 were myeloid leukemias arising by 12 months of age; and 12 were follicular center cell lymphomas found later in life. Of 6 endogenous ecotropic proviruses in SL/Kh, 2 were expressed in (SL/Kh x NFS) F1 backcrossed to NFS. One, encoded by a 27-kilobase EcoRI fragment, was closely linked to Gpi-1a on chromosome 7 and its expression seemed to be a prerequisite for the occurrence of all types of hemopoietic tumors. Microsatellite analysis of the backcross generation revealed multiple host genetic factors determining susceptibility to tumors. An allele derived from SL/Kh, mapped in the major histocompatibility locus on chromosome 17, was essential for development of early onset tumors. This locus was designated as Esl-1 (early lymphoma of SL-1). On the other hand, follicular center cell lymphomas developed mostly in the backcross mice homozygous for the NFS/N derived allele at the D4MIT17-linked locus, designated as foc-1 (follicular center cell lymphoma-1), on chromosome 4.

Animals↗

Presence of the diffuse early antigen of Epstein-Barr virus in lymphomas and lymphoproliferative disorders.

The authors recently demonstrated that 40% of Epstein-Barr virus (EBV) associated lymphoproliferative lesions contained lytic as well as latent EBV DNA. To examine more fully the replicative state of EBV in these disorders, the authors studied protein extracts of EBV-associated lymphoid lesions from 13 patients, most of whom were immunosuppressed, for expression of the diffuse early antigen (EA-D) of EBV, by immunoblotting techniques. The reagent used was a mouse monoclonal antibody. Seven of thirteen samples (54%) contained EA-D. These data indicate that in EBV-associated lymphoproliferative lesions, lytic viral replication occurs frequently, manifested by the presence of EBV diffuse early antigen as well as by the presence of lytic EBV DNA replication.

Antigens, Viral↗

Interaction between ozone and winter stress.

In some countries, ozone (O3) is primarily a summer pollutant, but in much of Europe, elevated concentrations occur outside the growing season so perennials and over-wintering annuals may be subjected to the combined stresses of pollution, plus chilling, freezing, and winter desiccation. It is recognised that some air pollutants modify the response of plants to environmental stress, but little is known of interactions involving O3. This paper is part of a programme concerned with the effects of O3 on resistance to chilling, freezing, and winter desiccation. Pea (Pisum sativum L.) was used as a convenient model to confirm that O3 affects freezing resistance. The experiment also served as a further evaluation of the use of induced chlorophyll fluorescence kinetics to detect latent O3 injury. Two cultivars, 'Feltham First' and 'Conquest', were fumigated for 7 days, 7 h day(-1). Diffusive resistance and induced fluorescence were recorded daily during the period, then the plants were hardened at 4 degrees C day/2 degrees C night before exposure to 0, -2, -4, -6 and -8 degrees C. Ozone (0.075 ppm; 150 microg O3 m(-3)) caused stomatal closure in both cultivars, but the response was more rapid in 'Conquest'. There were also rapid effects on fluorescence kinetics, and it was concluded that FR, the rate of rise of induced fluorescence, is a useful parameter for indicating latent injury and for distinguishing between cultivars of different sensitivity. Exposure to O3 increased freezing injury and led to greater electrolyte leakage. The freezing resistance of 'Feltham First' was more affected than that of 'Conquest', probably because of the slower stomatal response to the pollutant leading to greater flux of O3 to the internal tissues. It is concluded that interactions involving pollutants and winter stress have implications for crop loss assessment. Perennials and over-wintering annuals should be exposed to the full range of environmental stresses.

Journal Article↗