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[Clinico-electrophysiologic studies of experimental herpetic encephalitis].

Studies on animals demonstrated that in experimental herpetic encephalitis there is a diffuse retardation of background bioelectric brain activity and a proxysmal activity of 2 types: peek complex-slow waves 3 per 1 sec. and periodical paroxysmal complexes. There is also an increase of latent periods, duration and amplitudes of visual evoked potentials. Electrophysiological data correlate with the clinical picture of herpetic encephalitis and pathomorphological changes in the CNS. The obtained data are discussed with consideration bor the theory of neuron epileptization and hemodynamical disturbances.

Animals↗

Epstein-Barr virus detection in non-Hodgkin's lymphoma of the oral cavity: an immunocytochemical and in situ hybridization study.

OBJECTIVE: The purpose of this study was to histologically characterize a series of oral non-Hodgkin's lymphomas (NHLs) and to investigate latent and lytic Epstein-Barr virus (EBV) infection in these. STUDY DESIGN: The revised European-American Lymphoma classification system (41) was used to categorize 58 cases of oral NHL, which included 9 immunosuppression-related NHLs. EBV infection was determined by in situ hybridization for Epstein-Barr virus-encoded RNA and by immunohistochemistry for the EBV antigens latency membrane protein, Epstein-Barr nuclear antigen-2 (EBNA2) and Z EBV replication activator protein. RESULTS: Most tumors were B-cell lymphomas (78%), but the proportion of T-cell lymphomas was surprisingly high (22%). The most common histologic subtypes were diffuse large B-cell lymphomas (45%), peripheral T-cell lymphomas (19%), and follicle center lymphomas (14%). Two thirds of the known immunosuppression-related NHLs were T-cell lymphomas. All of the immunosuppression-related tumors were EBV-infected, whereas the EBV infection rate in the NHLs of the remaining patients presumed to be immunocompetent was only 9%. Most EBV-positive tumors expressed neither of the latent antigens (ie, latency membrane protein and Epstein-Barr nuclear antigen-2), and coexpression of the 2 was observed only in immunosuppressed patients. Z EBV replication activator protein expression, which is indicative of replicative infection, occurred only in immunosuppressed individuals. CONCLUSIONS: Diffuse large B-cell lymphomas were the most common histologic subtype of oral NHLs, but T-cell lymphomas were relatively common and frequently occurred in states of immunosuppression. EBV may play a limited role in the initiation of lymphoma in the immunocompetent patient, but the virus may be of importance in progression of the disease in those patients with more aggressive tumors, as immunosuppression occurs.

Adult↗

Modelling of mercury emissions from background soils.

Emissions of volatile mercury species from natural soils are believed to be a significant contributor to the atmospheric burden of mercury, but only order-of-magnitude estimates of emissions from these sources are available. The scaling-up of mercury flux measurements to regional or global scales is confounded by a limited understanding of the physical, chemical and biochemical processes that occur in the soil, a complex environmental matrix. This study is a first step toward the development of an air-surface exchange model for mercury (known as the mercury emission model (MEM)). The objective of the study is to model the partitioning and movement of inorganic Hg(II) and Hg(0) in open field soils, and to use MEM to interpret published data on mercury emissions to the atmosphere. MEM is a multi-layered, dynamic finite-element soil and atmospheric surface-layer model that simulates the exchange of heat, moisture and mercury between soils and the atmosphere. The model includes a simple formulation of the reduction of inorganic Hg(II) to Hg(0). Good agreement was found between the meteorological dependence of observed mercury emission fluxes, and hourly modelled fluxes, and it is concluded that MEM is able to simulate well the soil and atmospheric processes influencing the emission of Hg(0) to the atmosphere. The heretofore unexplained close correlation between soil temperature and mercury emission flux is fully modelled by MEM and is attributed to the temperature dependence of the Hg(0) Henry's Law coefficient and the control of the volumetric soil-air fraction on the diffusion of Hg(0) near the surface. The observed correlation between solar radiation intensity and mercury flux, appears in part to be due to the surface-energy balance between radiation, and sensible and latent heat fluxes which determines the soil temperature. The modelled results imply that empirical correlations that are based only on flux chamber data, may not extend to the open atmosphere for all weather scenarios.

Environmental Monitoring↗

Stochastic diffusion interactions and coarsening in a system of droplets growing from a supersaturated gas mixture.

In this work we study diffusion interactions among liquid droplets growing in stochastic population by condensation from supersaturated binary gas mixture. During the postnucleation transient regime collective growth of liquid droplets competing for the available water vapor decreases local supersaturation leading to the increase of critical radius and the onset of coarsening process. In coarsening regime the growth of larger droplets is prevailing noticeably broadening the droplet size-distribution function when the condensation process becomes more intensive than the supersaturation yield. Modifications in the kinetic equation are discussed and formulated for a stochastic population of liquid droplets when diffusional interactions among droplets become noteworthy. The kinetic equation for the droplet size-distribution function is solved together with field equations for the mass fraction of disperse liquid phase, mass fraction of water vapor component of moist air, and temperature during diffusion-dominated regime of droplet coarsening. The droplet size and mass distributions are found as functions of the liquid volume fraction, showing considerable broadening of droplet spectra. It is demonstrated that the effect of latent heat of condensation considerably changes coarsening process. The coarsening rate constant, the droplet density (number of droplets per unit volume), the screening length, the mean droplet size, and mass are determined as functions of the temperature, pressure, and liquid volume fraction.

Journal Article↗

Temporal relation between the ADC and DC potential responses to transient focal ischemia in the rat: a Markov chain Monte Carlo simulation analysis.

Markov chain Monte Carlo simulation was used in a reanalysis of the longitudinal data obtained by Harris et al. (J Cereb Blood Flow Metab 20:28-36) in a study of the direct current (DC) potential and apparent diffusion coefficient (ADC) responses to focal ischemia. The main purpose was to provide a formal analysis of the temporal relationship between the ADC and DC responses, to explore the possible involvement of a common latent (driving) process. A Bayesian nonlinear hierarchical random coefficients model was adopted. DC and ADC transition parameter posterior probability distributions were generated using three parallel Markov chains created using the Metropolis algorithm. Particular attention was paid to the within-subject differences between the DC and ADC time course characteristics. The results show that the DC response is biphasic, whereas the ADC exhibits monophasic behavior, and that the two DC components are each distinguishable from the ADC response in their time dependencies. The DC and ADC changes are not, therefore, driven by a common latent process. This work demonstrates a general analytical approach to the multivariate, longitudinal data-processing problem that commonly arises in stroke and other biomedical research.

Animals↗

The characteristics of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma: comparison between EBV(+) and EBV(-) cases in Japanese population.

We have investigated 114 cases with diffuse large B-cell lymphoma (DLBCL) to clarify the characteristics of DLBCL with Epstein-Barr virus (EBV) infection. Thirteen cases (11.4%) showed EBV-encoded RNA 1 (EBER1) signals by RNA in situ hybridization. EBV-encoded latent membrane protein 1 (LMP1) and EBV-encoded nuclear antigen 2 (EBNA2) were expressed in 11 and 4 cases, respectively. Expression of CD30, Bcl-6 and immunoglobulin (Ig) was found in 92%, 31% and 23% with EBV(+) DLBCL, and in 15%, 79% and 82% with EBV(-) DLBCL, respectively. The sequence of rearranged Ig heavy chain (IgH) variable (V) region gene was analyzed in 5 cases with EBV(+) DLBCL and 61 cases with EBV(-) DLBCL. Somatic mutation was found in all cases except one with EBV(-) DLBCL. Average mutation frequency was 9.6% in EBV(+) DLBCL vs. 11.5% in EBV(-) DLBCL. The rates of replacement mutation vs. silent mutation (R / S values) in complementarity determining region II and framework region III were 2.7 and 1.5 in EBV(+) DLBCL, 2.6 and 1.4 in EBV(-) DLBCL. Crippling mutation generating a stop codon was found in 2 of 5 cases (40%) with EBV(+) DLBCL, but none of 61 cases (0%) with EBV(-) DLBCL. These findings suggest that EBV(+) DLBCL and EBV(-) DLBCL were both derived from germinal center (GC) or post-GC B cells, and EBV(+) DLBCL frequently have a non-functional IgH gene owing to crippling mutation.

Adolescent↗

Natural killer-like T-cell lymphoma of the parotid in a patient infected with human immunodeficiency virus.

A 42-year-old man with acquired immunodeficiency syndrome developed a mass of the right parotid gland and multiple hepatic masses. Hematoxylin-eosin-stained sections of the parotid lesion showed a diffuse infiltrate of large mononuclear cells with vesicular nuclei and prominent nucleoli, consistent with a non-Hodgkin lymphoma. Immunohistochemical stains demonstrated expression of the T-cell markers CD3 and UCHL-1, as well as latent membrane protein 1 and T-cell intracellular antigen 1. Flow cytometry showed surface expression of CD2, CD3, CD7 (dim), CD8, and CD56. CD5 was not expressed. Molecular evaluation by polymerase chain reaction demonstrated monoclonal rearrangement of the T-cell receptor gamma gene. Epstein-Barr virus early RNA and human immunodeficiency virus RNA were demonstrated by in situ hybridization. To our knowledge, this is the first reported case of T-cell lymphoma of the parotid in a patient infected with human immunodeficiency virus. After 2 separate chemotherapy regimens, the patient achieved clinical remission for 1(1/2) years; he then developed progressive pulmonary lesions and died.

Adult↗

[Pyothorax-associated lymphoma: EBV-positive lymphoma developing in immunocompetent patients].

Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most of PALs are diffuse lymphomas of B cell type and contain Epstein-Barr virus (EBV) DNA. We established two lymphoma cell lines from biopsy specimens of PAL cases, and examined their growth characteristics and the expression of EBV latent infection genes and oncogenes. The differences in growth rate and oncogene expression between the lines could not be adequately explained by the pattern of EBV latent gene expression. The subsequent genetic lesions might be necessary for the development of overt lymphoma. Furthermore, the mechanism of development of viral antigen-positive tumor in immunocompetent patients is discussed.

Empyema, Pleural↗

Herpes simplex virus type 1 immediate-early protein ICP0 diffuses out of infected rabbit corneas.

Herpes stromal keratitis (HSK) results from infection of herpes simplex virus (HSV) in the cornea. Recurrent HSV infection is a leading cause of corneal scarring and visual loss. Although it is generally thought that HSK is the result of an immune response to one or more viral proteins, no viral proteins have been detected in HSK corneas. Thus, the viral proteins involved in HSK, if any, remain undetermined. In contrast, it is reported here that when HSK corneal buttons from latently infected rabbits were fixed using standard procedures, the important immediate-early HSV-1 protein ICP0 was readily detected in the fixative by Western blotting. Similarly, when HSK corneal buttons were soaked in buffer (rather than fixative), ICP0 was readily detected in the soaking buffer. Other HSV-1 proteins were not detected either in the fixative or in the soaking buffer. It is also reported here that ICP0 was consistently detected in virus-free tears from the eyes of rabbits acutely infected with HSV-1. These results suggest that ICP0 rapidly diffuses out of the cornea and may explain why ICP0 was detected in the fixative of HSK corneas and in the soaking buffer of acutely infected corneas.

Animals↗

Contribution of Epstein-Barr virus to development of malignant lymphoma of the thyroid.

Epstein-Barr virus (EBV)-related mRNA, their products and apoptosis were investigated in 32 cases of malignant lymphoma of the thyroid (MLT) and 30 cases of Hashimoto's thyroiditis (HT) by in situ hybridization, immunohistochemistry and nick end labeling method on routinely processed tissue sections. In MLT, EBV-encoded small RNA (EBER) were detected in three cases, consisting of a follicular, predominantly large cell type (FL), a diffuse, large cell type (DL) and a large cell, immunoblastic type (IBL). In EBER-positive cases, IBL that was positive for T cell marker, exhibited neither BamHl H Left Frame 1 (BHLF1) transcript, EBV-encoded latent membrane protein (LMP) nor BamHl Z Left Frame 1 (BZLF1) gene product (ZEBRA), whereas both BHLF1 and ZEBRA were found in a small portion of the tumor cells in the FL and DL that expressed B cell marker and LMP. Apoptotic cells were observed in only a few lymphocytes in HT, and in a few non-neoplastic lymphocytes and various numbers of lymphoma cells in MLT. The apoptotic cell ratio of MLT tended to be higher in lower grade lymphomas. These results suggest that EBV may participate in the malignant transformation from HT to MLT.

Adult↗

Pyothorax-associated lymphoma: relationship with Epstein-Barr virus, human herpes virus-8 and body cavity-based high grade lymphomas.

Pyothorax-associated lymphoma (PAL) is a newly-described entity developing several decades after artificial pneumothorax treatment for pulmonary or pleural tuberculosis. It is known to be associated with Epstein-Barr virus (EBV) with constant expression of the two latent membrane proteins: latent membrane protein (LMP)-1 and EBV-associated nuclear antigen (EBNA)-2. We are reporting three new cases of PAL. All of the tumours were of B-cell lineage and classified as large-cell diffuse lymphomas according to the International Working Formulation for the Classification of Lymphomas. The EBV genome was detected in two of the cases with LMP-1 and EBNA-2 expression. No EBV could be detected in the third case suggesting that different mechanisms may be involved in the pathogenesis of the disease. Body cavity-based high grade lymphomas (BCBL) represent a new disease, developing mainly in human immunodeficiency virus (HIV) infected patients: the tumoural cells often contain both human herpes virus (HHV)-8 (or Kaposi's sarcoma herpes virus) and EBV genomes, suggesting that these viruses might co-operate in the pathogenesis of the disease. The pleural location and the association of EBV have led to speculation that PAL could also be related to HHV-8 infection. However, no HHV-8 genome could be detected in any of the 14 tested cases already reported in the literature nor in the two cases we studied (one EBV-positive and one EBV-negative), suggesting that PAL and BCBL are two different entities.

Aged↗

In situ demonstration of Epstein-Barr virus small RNAs (EBER 1) in acquired immunodeficiency syndrome-related lymphomas: correlation with tumor morphology and primary site.

Some acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARLs) are infected with Epstein-Barr virus (EBV), although the frequency and importance of this association is disputed. Using paraffin section RNA in situ hybridization (ISH) with digoxigenin-labeled riboprobes, we screened 16 central nervous system (CNS) non-Hodgkin's lymphomas (NHLs), 101 systemic NHLs, and 11 Hodgkin's disease cases arising in human immunodeficiency virus-seropositive individuals for EBV-encoded small RNA (EBER 1) expression, an EBV gene product transcribed in abundance during latent infection. Tumor cells contained EBV in 85 of 128 ARLs (66%), but infection rates differed with lymphoma type. EBER 1 was expressed in tumor cells in 11 of 11 Hodgkin's disease cases (100%), 15 of 16 CNS NHLs (94%), and 46 of 60 systemic immunoblast-rich/large-cell lymphomas (77%), but in only 12 of 35 Burkitt-type (small noncleaved cell) (34%) and 1 of 6 monomorphic centroblastic (diffuse large noncleaved cell) (17%) lymphomas. In most EBV-positive ARLs, all recognizable viable tumor cells expressed EBER 1. We conclude that (1) EBV infects tumor cells in all AIDS-related Hodgkin's disease cases, in virtually all primary CNS ARLs, and in most systemic immunoblast-rich/large-cell ARLs; (2) only a minority of Burkitt-type and monomorphic centroblastic lymphomas are associated with EBV; and (3) EBER-ISH is ideal for the histopathologic detection of latent EBV in routine tissue specimens.

B-Lymphocytes↗

Cooperation of EBV DNA polymerase and EA-D(BMRF1) in vitro and colocalization in nuclei of infected cells.

Expression of the Epstein-Barr virus (EBV) DNA polymerase (EBVpol) open reading frame (BALF5) by in vitro transcription-translation yielded a 116-kDa primary translation product. Enzymatic DNA polymerase activity of the in vitro translated polypeptide required the presence of the 47-kDa BMRF1 (EA-D) gene product. Antiserum raised to the BALF5 gene product expressed in Escherichia coli specifically precipitated a 116-kDa polypeptide in extracts of latently infected lymphoblastoid cells induced for EBV replication. Immunofluorescence microscopy revealed colocalization of the EBVpol and EA-D(BMRF1) to discrete foci within the nuclei of induced cells; however, the blockade of viral DNA synthesis resulted in diffuse nuclear staining patterns for both antigens. Bromodeoxyuridine staining of these discrete foci colocalizing with EBVpol suggests that they are sites of early viral DNA synthesis. These observations suggest that EA-D(BMRF1) may be an accessory protein of the EBV DNA polymerase which colocalizes in vivo with EBVpol to sites of viral DNA replication and cooperates in vitro to form an active EBVpol holoenzyme.

Antigens, Viral↗

Metastatic tumors to the spleen: a 25-year clinicopathologic study.

OBJECTIVE: The clinicopathologic features of splenic metastases have seldom been investigated. The aim of this study was to evaluate the clinical and pathological impact of splenic metastases. CASE MATERIAL: We reviewed the clinical/autopsy records and pathologic features of 92 Chinese patients (58 men, 34 women) with secondary nonlymphoid splenic tumors recorded during a 25-year period. RESULTS: The incidence of splenic secondary tumors at autopsy was 0. 6% and at splenectomy, 1.1%. The lesions were often seen in elderly patients (mean age, 60 years). Seven (8%) of the splenic lesions were symptomatic. The symptomatic splenic lesions, as compared with asymptomatic lesions, were bigger and were found more often in women and younger patients. Two patients experienced spontaneous splenic rupture because of metastatic carcinoma. Eighty-seven (95%) of the secondary splenic tumors were carcinomas. Lung was the most common primary tumor site (21%), followed by the stomach (16%), pancreas (12%), liver (9%), and colon (9%). Rarely reported sources of primary tumor, such as esophageal carcinomas, nasopharyngeal carcinoma, and choriocarcinoma, were also found. Splenic metastases could be identified macroscopically in 74 (80%) of our patients. Grossly, splenic metastases involved the splenic capsule (n = 8) or were solitary (n = 31), multiple (n = 30), or diffuse (n = 8) lesions in the splenic parenchyma. Isolated splenic metastases were noted in 5.3% of the metastases found at autopsy. Many of the metastatic lesions in the spleen were identified shortly after primary tumors were detected (mean latent period, 6.7 months). The time from diagnosis of the primary tumor to metastasis to the spleen was more than 2 years in 14 patients. CONCLUSIONS: Splenic metastases are uncommon. A variety of clinical and pathologic patterns were noted in our series.

Age Factors↗

[Lyme borreliosis in neurology and psychiatry].

Neurological manifestations of Lyme disease are as multifarious as the entire spectrum of this common infection. In stage I, fibromyalgia and, more rarely, painful muscular fasciculation, dominate the clinical picture. In the individual case, mild psychic abnormalities may already be observed. Characteristic of the 2nd stage is lymphocytic meningopolyneuritis. Involvements of the CNS are expressed not so much in focal deficits, as in diffuse psychopathological disorders. In stage 3, CNS manifestations are characterized by chronic, in part multifocal, encephalitides and encephalomyelitides, isolated transverse myelitides and cerebral vasculitic disorders. The clinical symptomatology may be dominated by severe psychiatric syndromes. Connatal and subclinical latent infections of the nervous system with Borrelia represent special forms.

Diagnosis, Differential↗

[Spastic paraplegia in Sjögren's syndrome associated with mixed connective tissue disease (MCTD)--a case report].

A case of spastic paraplegia in Sjögren's syndrome associated with mixed connective tissue disease is reported. In this 49-year-old woman spastic gait and arthralgia developed at the age of 23 years and progressed chronically. On neurologic examination, supranuclear paresis of facial nerve was observed. Deep tendon reflexes were hyperactive in the jaw, upper and lower extremities. Serological tests showed that anti-nuclear, anti-RNP, and anti-SS-A antibodies were positive. Spinal fluid analysis showed that rate of de novo central nervous system (CNS) IgG synthesis was increased, and C3/C4 ratio was elevated. CT scans of the brain showed calcifications at bilateral basal ganglia, dentate nucleus and cerebellar vermis. An electroencephalogram revealed diffuse slowing, and 123I-IMP brain scans revealed decreased cerebral blood flow. MRI of brainstem and cervical cord were normal. These findings suggested that corticospinal tracts upper the brainstem were severely affected, and that there were multifocal latent lesions in the CNS. Mechanisms of the CNS involvement were supposed to be both autoimmune abnormality in the CNS, and vascular impairment.

Central Nervous System Diseases↗

Epstein-Barr virus and gastric carcinoma in Western patients: comparison of pathological parameters and p53 expression in EBV-positive and negative tumours.

AIMS: The presence of Epstein-Barr virus (EBV) was studied in 56 gastric carcinomas from Western patients by in-situ hybridization for EBV-encoded RNAs (EBER). EBV-positive and negative carcinomas were compared for various pathological parameters including p53 overexpression. METHODS AND RESULTS: EBERs transcripts were detected in seven cases overall: four cases of 52 conventional carcinomas (7. 7%) and three cases of four gastric carcinomas with lymphoid stroma (75%). EBER positivity was diffuse in five cases and restricted to a localized area of the tumour in two cases of conventional carcinoma. A monoclonal EBV genomic pattern was demonstrated in the case tested by Southern blot analysis. By immunohistochemical analysis, neither EBV latent or lytic cycle proteins nor C3d/EBV receptor were expressed by neoplastic cells. EBER positivity was significantly correlated with prominent lymphoid reaction (P = 0.0002) which was associated with numerous PS100-positive dendritic cells and with HLA-DR expression by tumour cells (P = 0.03). p53 immunoreactivity in more than 30% of tumour cells was detected in 25 out 49 EBV-negative cases and was absent in EBV-positive cases except in one case with focal EBER-positivity. CONCLUSIONS: Focal staining for EBER is an unusual finding in the setting of gastric carcinoma and these results suggest that there might be two types of EBV-associated gastric carcinoma in which the viral infection will play a different role. The presence of a stromal lymphoid reaction which is strongly correlated with EBV positivity, is associated with antigen-presenting ability by HLA-DR-positive tumour cells or abundant dendritic cells. The function of p53 appears preserved in all EBV-associated carcinomas except in one case with focal EBER expression whereas the immunohistochemical pattern of p53 is suggestive of a mutational phenomenon in 51% of EBV-negative cases.

Female↗