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PubMed1998

Primary central nervous system lymphomas in 72 immunocompetent patients: pathologic findings and clinical correlations. Groupe Ouest Est d'étude des Leucénies et Autres Maladies du Sang (GOELAMS)

We reviewed 72 primary central nervous system lymphomas occurring in immunocompetent patients. The cases were reviewed for clinical data, histology, immunophenotype, bcl-2 and p53 expression, and Epstein-Barr virus association. Follow-up was available for 40 patients included in the Groupe Ouest Est d'étude des Leucénies et Autres Maladies du Sang (GOELAMS) lymphomes cérébraux primitifs (LCP 88) trial. Each diagnosis, requiring a consensus among at least 3 pathologists, was performed according to the recent Revised European-American Lymphoma classification and equivalents in the updated Kiel classification. Tumors were predominantly classified as diffuse large B-cell lymphomas. There were 3 T-cell lymphomas and 1 Hodgkin lymphoma. The proteins bcl-2 and p53 were expressed in 35% and 16% of the tested cases, respectively. Epstein-Barr virus was not found by in situ hybridization except in the case classfied as a cerebral localization of Hodgkin disease. No significant association was found between subtypes, bcl-2 or p53 expression, and patient survival. From the standpoint of their biologic characteristics, primary central nervous system lymphomas are very similar to systemic diffuse large B-cell lymphomas. In contrast to AIDS-related primary central nervous system lymphomas, primary central nervous system lymphomas are rarely associated with Epstein-Barr virus and in immunocompetent patients they express bcl-2 at a relatively low rate.

Adult↗
PubMed1989

Molecular genetic analysis of three AIDS-associated neoplasms of uncertain lineage demonstrates their B-cell derivation and the possible pathogenetic role of the Epstein-Barr virus.

Each of three individuals with acquired immunodeficiency syndrome (AIDS) developed a pleomorphic malignant neoplasm in which a precise histopathologic diagnosis could not be rendered. In each case, the tumor cells expressed leukocyte common antigen and a variable constellation of antigens associated with B- and T-cell activation (HLA-DR, T9, T10, BL2, BL3, Ki-24, BLAST-2). They lacked all B cell, T cell, myeloid, and monocyte lineage-restricted antigens, resulting in their classification as hematopoietic neoplasms of uncertain lineage. However, antigen receptor gene rearrangement analysis demonstrated that each of these three neoplasms exhibited clonal immunoglobulin heavy chain and kappa light chain gene rearrangements and lacked T-cell receptor beta chain gene rearrangements and therefore were B cell-derived non-Hodgkin's lymphomas (NHL) representative of an equivalent, relatively mature stage of B-cell differentiation. In contrast with most AIDS-associated NHLs, each of these three neoplasms lacked c-myc gene rearrangements and contained Epstein-Barr virus (EBV) proteins and/or sequences. These studies demonstrate that these three AIDS-associated neoplasms of uncertain lineage exhibit a strikingly similar constellation of distinctly uncommon morphologic, immunophenotypic, and molecular genetic characteristics that distinguishes them substantially from the vast majority of NHLs that have been reported to occur in association with AIDS. The consistent presence of EBV proteins and/or DNA sequences suggests that the Epstein-Barr virus played a pathogenetic role in the development of these three AIDS-associated neoplasms. Finally, these studies further illustrate the utility of antigen receptor gene rearrangement analysis in the diagnosis and classification of hematopoietic neoplasms of uncertain lineage.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Serotype classification and characterisation of the rotavirus SA11 VP6 protein using mass spectrometry and two-dimensional gel electrophoresis.

VP6, which makes up the inner capsid of rotavirus, is the major structural protein of this virus. Whilst VP6 has been sequenced at the DNA level in several rotavirus strains, there has been less effort to characterise the protein at the amino acid level. This paper reports the use of peptide mass fingerprinting and post-source decay fragmentation studies using MALDI-TOF and electrospray ionisation mass spectrometry to identify and characterise, in detail, the VP6 protein. We show that mass spectrometric analysis of VP6 peptides successfully distinguished SA11 from other rotavirus serotypes, and identify unique peptides that can be used for serotypic differentiation. For VP6 characterisation, the ExPASy FindMod tool was used to predict post-translational modifications on the protein. Analysis of trypsin and AspN digests predicted that the N-terminal methionine of VP6 was acetylated and this was confirmed using post source decay and electrospray ionisation mass spectrometry-mass spectrometry. An asparagine residue (aa107), which is followed by a glycine residue, was shown to undergo partial deamidation to aspartic acid. VP6 has two additional asparagine-glycine sequences and, in this sequence context, asparagine is known to be particularly susceptible to deamidation. Two-dimensional gel electrophoresis revealed a complex series of VP6 isoforms with an apparent molecular mass of approximately 45,000 Da and a pI ranging from 5.25 to 5.8. This pattern could partly be explained by the potential for deamidation at several sites within the protein.

Acetylation↗
PubMed1993

Pupil cycle time and human immunodeficiency virus (HIV) infection.

The pupil cycle time (PCT) was measured in 22 HIV-positive patients and 22 age/sex-matched controls. Of the HIV-positive group, 13 (59%) met the Centre for Disease Control classification of acquired immunodeficiency syndrome (AIDS) defining illness. There was a highly statistically significant difference in the PCT between the HIV-infected group and the control group (p < 0.0001, Student's t-test). Within the HIV-infected group there was no statistically significant difference in the PCT between those patients with full-blown AIDS and the others. This study suggests that HIV infection may be associated with subclinical ocular autonomic dysfunction even in the earlier stages of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Analysis of domain structural class using an automated class assignment protocol.

The extent to which the contemporary dataset of protein structures can be segregated into four structural "classes" as originally defined by Levitt & Chothia in 1976 is examined and a simple method presented for the assignment of protein domains into these classes. Assignments are based on known three-dimensional structures, and for successful assignment it was found that helix/sheet content, contacts between secondary structures and their sequential order had to be used. The procedure attempts to maximise the automatic separation into classes for a dataset of 197 manually classified, non-homologous domains. It was found that approximately 90% of the structures were classified automatically; the remainder were borderline and were left for manual inspection. The method was then applied to a test set of 43 protein domains with similar results. The data support the concept of distinct classes of protein structure, although a few intermediate structures are found, demonstrating that it is possible to define relatively simple parameters complying with commonly accepted nomenclature that automatically define 90% of protein domains with essentially 100% accuracy. However, re-examination of the data also suggested that the previously separate alpha/beta and alpha + beta classes show considerable overlap and are more naturally represented as a single alpha beta class. This large alpha beta class can then be most easily subdivided by consideration of whether the sheets are mainly parallel, antiparallel or mixed. The correlation between structural class and function is discussed, together with the conservation of class within a sequence superfamily. This represents the first step in an automated phenetic description of protein structure complementing the usual phylogenetic approach to protein structure classification.

Algorithms↗
PubMed2005

Cardiac surgery in patients with liver cirrhosis.

BACKGROUND: Cardiac surgery was infrequently performed in patients with liver cirrhosis, and its clinical outcome has been reported only in small series. We sought to evaluate the clinical outcome of cardiac operation in patients with noncardiac liver cirrhosis. METHODS: Data were collected by a retrospective case note review. The preoperative, intraoperative, and postoperative variables were recorded. The severity of liver cirrhosis was graded using the Child-Pugh classification. RESULTS: Between January 1993 and May 2004, 18 patients with liver cirrhosis underwent cardiac surgery at the authors' hospital. Thirteen patients had hepatitis virus infection, and 5 cases were alcohol related. Thirteen patients were classified as Child A cirrhosis, 4 were class B, and 1 was class C. Sixteen patients underwent cardiac surgery with the use of cardiopulmonary bypass, and 2 patients underwent off-pump coronary artery bypass surgery. The overall in-hospital mortality rate was 6% (1 of 18), and there was no death in 5 class B and C cirrhotic patients. The rate of major complication was 39% in class A and 80% in class B and C. CONCLUSIONS: Although the postoperative complication was common, cardiac operation could be performed safely in patients with mild and advanced liver cirrhosis.

Adult↗
PubMed1996

[Diagnostic value of portal duplex ultrasound in liver cirrhosis].

AIM: In a prospective study we investigated if the endoscopical evaluation of the bleeding risk of esophageal varices in cirrhotics could be improved by additional duplex sonography of the portal vein. METHOD: The trial involved 41 patients with endoscopically diagnosed esophageal varices (27 male, 14 female) who were followed up over a period of 30 months (mean of 13 +/- 3). According to the Child-Pugh-Turcotte -classification, 14 patients were classified as grade A, another 14 as grade B, and 13 as grade C. The cause of the cirrhosis included virus infection (n = 14), alcohol (n = 17) and miscellaneous disorders (n = 9, primary biliary = 3, autoimmune = 2, idiopathic = 4). RESULTS: During the observation time, 17 patients who developed an acute esophageal variceal hemorrhage were put in the bleeding group (mean portal flow velocity Vm = 9.29 +/- 3.31 cm/s, mean flow volume Fm = 371 +/- 173 ml/min), while the remaining 24 patients formed the non-bleeding group (Vm = 13.29 +/- 5.12 cm/s, FV = 500 +/- 200 ml/min). The bleeding group had significantly lower mean portal flow velocities (p < 0.017) and mean flow volumes (p < 0.05) than the non-bleeding group. By adopting cut-off values of 12 cm/s for Vm and 420 ml/min for FV we obtained a diagnostic sensitivity for predicting esophageal variceal hemorrhage of 0.88 and 0.65 respectively. CONCLUSION: Portal duplex sonography may improve the evaluation of bleeding risk in patients wit endoscopically diagnosed esophageal varices and could influence the decision for prophylactic treatment.

Adult↗
PubMed2006

Laparoscopic incisional and umbilical hernia repair in cirrhotic patients.

BACKGROUND: Traditional approach to incisional hernias (IHs) in cirrhotic patients is plagued by a significant recurrence rate and frequent wound infections. The laparoscopic repair of IHs was designed to offer a minimally invasive and tension-free technique that yields less morbidity and fewer recurrences than the standard open repair. In cirrhotic patients there are additional reasons for the benefits of laparoscopy. First, preservation of the abdominal wall avoids interruption of large collateral veins. Second, nonexposure of viscera restricts electrolytic and protein losses, and improves absorption of ascites. Finally, the laparoscopic approach is associated with a lower perioperative blood loss (smaller abdominal incision). METHODS: A retrospective review was performed for 14 consecutive patients with ventral hernias and affected by chronic hepatitis or cirrhosis related to hepatitis C-B virus, who underwent laparoscopic repair at our institution between September 2002 and October 2004. All patients were in class A of Child-Pugh classification. RESULTS: There was no conversion to open operation. The mean size of the defects was 87 cm (range 1 to 480); incarceration was present in 2 patients and multiple (Swiss-cheese) defects in 1. In all cases, the mesh (average, 287 cm) was secured with transabdominal sutures and metal tacks or staples leaving the sac in situ. Operative time and estimated blood loss averaged 88 min (range 18 to 270) and 30 mL (range 10 to 150). Length of hospital stay averaged 2.6 days (range 1 to 6). There were 11 minor complications: seroma lasting >4 weeks (5), postoperative ileus (2), suture site pain >2 weeks (2), urinary retention (1), and skin breakdown (1). We experienced no recurrences with an average follow-up of 8 months (range 3 to 24). CONCLUSIONS: Laparoscopic IH repair is technically feasible and safe even in cirrhotic patients with fascial defects. This operation decreases postoperative pain, shortens the recovery period, and seems to reduce postoperative morbidity and recurrence. To the best of our knowledge, this is the first report in which a series of cirrhotic patients affected by incisional and umbilical hernias is treated with a laparoscopic approach.

Aged↗
PubMed1994

Molecular evolution of herpesviruses: genomic and protein sequence comparisons.

Phylogenetic reconstruction of herpesvirus evolution is generally founded on amino acid sequence comparisons of specific proteins. These are relevant to the evolution of the specific gene (or set of genes), but the resulting phylogeny may vary depending on the particular sequence chosen for analysis (or comparison). In the first part of this report, we compare 13 herpesvirus genomes by using a new multidimensional methodology based on distance measures and partial orderings of dinucleotide relative abundances. The sequences were analyzed with respect to (i) genomic compositional extremes; (ii) total distances within and between genomes; (iii) partial orderings among genomes relative to a set of sequence standards; (iv) concordance correlations of genome distances; and (v) consistency with the alpha-, beta-, gammaherpesvirus classification. Distance assessments within individual herpesvirus genomes show each to be quite homogeneous relative to the comparisons between genomes. The gammaherpesviruses, Epstein-Barr virus (EBV), herpesvirus saimiri, and bovine herpesvirus 4 are both diverse and separate from other herpesvirus classes, whereas alpha- and betaherpesviruses overlap. The analysis revealed that the most central genome (closest to a consensus herpesvirus genome and most individual herpesvirus sequences of different classes) is that of human herpesvirus 6, suggesting that this genome is closest to a progenitor herpesvirus. The shorter DNA distances among alphaherpesviruses supports the hypothesis that the alpha class is of relatively recent ancestry. In our collection, equine herpesvirus 1 (EHV1) stands out as the most central alphaherpesvirus, suggesting it may approximate an ancestral alphaherpesvirus. Among all herpesviruses, the EBV genome is closest to human sequences. In the DNA partial orderings, the chicken sequence collection is invariably as close as or closer to all herpesvirus sequences than the human sequence collection is, which may imply that the chicken (or other avian species) is a more natural or more ancient host of herpesviruses. In the second part of this report, evolutionary relationships among the 13 herpesvirus genomes are evaluated on the basis of recent methods of amino acid alignment applied to four essential protein sequences. In this analysis, the alignment of the two betaherpesviruses (human cytomegalovirus versus human herpesvirus 6) showed lower scores compared with alignments within alphaherpesviruses (i.e., among EHV1, herpes simplex virus type 1, varicella-zoster virus, pseudorabies virus type 1 and Marek's disease virus) and within gammaherpesviruses (EBV versus herpesvirus saimiri).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoviridae↗
PubMed2004

Hepatitis C virus and risk of non-Hodgkin lymphoma: a population-based case-control study among Connecticut women.

OBJECTIVES: Previous epidemiologic studies of hepatitis C virus (HCV) infection and B-cell non-Hodgkin lymphoma (B-NHL) have yielded conflicting results, perhaps due to differences in the classification of B-NHL and the choice of non-population-based control groups that may not reflect the background population prevalence of HCV. To further investigate the link between HCV and NHL, we conducted HCV testing on serum samples of 998 women (464 cases; 534 controls) from a population-based case-control study of women in Connecticut. METHODS: Serum samples were screened for HCV antibodies using an enzyme immunoassay; positive samples were confirmed by additional testing for HCV antibodies and for serum HCV RNA. RESULTS: Approximately 2% (8 of 464) of cases and 1% (5 of 534) of controls tested positive for HCV. The risk of NHL associated with HCV infection appeared to be concentrated among B-cell lymphomas [odds ratio (OR) 2.0; 95% confidence interval (CI) 0.6, 8.2], particularly among follicular lymphomas (OR 4.1, 95% CI 0.8, 19.4). CONCLUSIONS: The primary strength of this study is our use of a population-based study design, although the low prevalence of HCV among women in Connecticut resulted in wide CIs for the estimated association between HCV and B-NHL subtypes. Our study suggests that HCV may be associated with increased risk of development of B-NHL, and that this risk may vary by B-NHL subtype among women. Due to the relatively low prevalence of HCV in our study population and the scarcity of population-based epidemiological research on this subject, our study highlights the need for additional large, population-based studies of the role of HCV in the etiology of B-NHL.

Adult↗
PubMed1989

[Disorders of the nervous system associated with the acquired immunodeficiency syndrome (AIDS)-clinical approach].

The acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV) and characterized by disorders of the nervous system in addition to opportunistic infection and cancer. Centers for Disease Control (CDC) recommend the classification system consisting of four major groups. Group I is patients with acute HIV infection, and Group II is asymptomatic carriers. Group III is those with persistent generalized lymphadenopathy (PGL). Group IV includes five subgroups: IVA with constitutional disease, IVB with neurologic disease, IVC with secondary infectious diseases, IVD with secondary cancers and IVE with other conditions. The nervous system disorders are classified into two types: one is produced by HIV itself and not directly related to immunodeficiency, and the other caused by opportunistic infectious agents and cancers. The former is further divided into two kinds: atypical aseptic meningitis and acute inflammatory demyelinating polyneuropathy (AIDP) occur mainly in Group I and II, whereas HIV encephalopathy, distal symmetric polyneuropathy (DSPN) and vacuolar myelopathy in Group III and IV. Group I or II patients have no apparent medical problems. Therefore, when neurologists see patients with risk factors for HIV infection presenting with atypical meningitis or AIDP, it is of utmost importance to have a high index of suspicion and to look for evidence of HIV infection.

AIDS Dementia Complex↗
PubMed1975

Serologic classification of feline caliciviruses by plaque-reduction neutralization and immunodiffusion.

Serologic classification of 14 isolated of feline caliciviruses was carried out, using plaque-reduction neutralization tests. Sixty to 200 plaque-forming units of virus were employed against 20 antibody units of hyperimmune goat antiserums prepared to individual isolates. The results established that these viruses were related in various degrees, but no 2 were identical. Arrangements in order of the greatest intergroup reactions yielded essentially 1 serotype with the exception of 1 virus showing 1-way neutralization reactions with heterologous isolates. The geographic origin, the site of viral isolation, or the plaque size had no relationship with the neutralization pattern. The F-9 isolate that showed the greatest intergroup reactions was proposed as the possible reference virus. The viruses were indistinguishable by using gel-diffusion analysis against cat antiserums.

Animals↗
PubMed1989

The epidemiology of leukemias (past, present, future).

There are three periods of the history of the epidemiology of leukemias. The first period is characterized by 3 features: the description of the occupational leukemias (radiations, benzene) with more recently the war leukemias (Hiroshima), the leukemia induced by chemotherapy; the description of the leukemias of animals induced by viruses (chicken, mice and more over cats); and the concept of the geographical hematology. The second period may be called "Burkitt period" so important are the consequences of the discoveries made in Uganda. The third period is Japanese and American with the leukemias induced by the virus HTLV 1 and the recent extensions. Such is the past. The present is defined by strong data (diversity of causes, diversity of the combinations of causes, of the etiologic pluralism), and by persisting weaknesses (epidemiology, classification of leukemias). Three ways for the future: induction, prediction, and correlation with the hope of an efficient prevention.

Animals↗
PubMed1975

Purification and electron microscopy of lactic dehydrogenase virus of mice.

Lactic dehydrogenase virus (LDV) was purified from infectious ascites fluid of mice bearing Ehrlich tumours using Sepharose gel filtration and rate zonal and isopycnic sedimentation. In glycerol gradients, a sedimentation coefficient of about 200S and a buoyant density of 1-14 g/ml was determined for the virus particle. Spherical particles with diam. between 62 and 80 nm, depending on the method of fixation and staining, have been identified electron microscopically. The virus particle consists of a spherical nucleocapsid wrapped into a double-layered envelope. The nucleocapsids, isolated by treatment with NP40 and purified by centrifuging on sucrose gradients had a sedimentation coefficient of 176S. Electron micrographs show spherical particles with a diam of 35 plus or minus nm. Classification of LDV as a member of the togaviridae family is discussed.

Animals↗
PubMed1984

Studies on the induction of histocompatibility gene mutations in germ cells of mice by chemical mutagens and/or virus-inducing compounds.

This work continues earlier studies concerning the use of histocompatibility mutations in mammalian germ cells as a mutagenicity test system (H test). The rate of spontaneous H mutations was re-examined using a new basis for the classification of H mutants. This procedure led to very high frequencies of suspected spontaneous H mutants: among C57Bl/6 mice, 6% and among C3H mice, 9%. F2 hybrids of a cross between these strains revealed 1% suspected H mutants. Using the same procedure, the sensitivity of the H test was examined with the mutagens ethylnitrosourea, benzo[a]pyrene, 2-acetylaminofluorene (2-AAF), with the solvent dimethyl sulfoxide (DMSO) and with the antibacterial nitrofurantoin. It was possible to demonstrate the mutagenic potential of all mutagens tested as well as their specific action on the different stages of male germ cell development. We succeeded in demonstrating the mutagenicity of 2-AAF for the first time in germ cells of a mammal. In contrast to the negative result with benzopyrene (BP) in the specific locus test, BP induced H mutants even at the very low dose of 2 mg/kg. DMSO was found to induce H mutations in spermatogonia. This extraordinary result is possibly due to the virus-inducing properties of this compound. Nitrofurantoin which is often used in treating bacterial infections of the urinary tract in humans showed a very stage-specific action on maturing spermatids. The value of the H test for mutagenicity testing is discussed with respect to its sensitivity and economy. The very high spontaneous frequency of suspected H mutants and the ease of inducing increased mutant frequencies by mutagens and by DMSO suggest the possibility that the majority of the histoincompatibilities found in the H test are due to induced antigenic gene products of endogenous viruses. This, however, does not interfere with the applicability of the H test for mutagenicity testing, but rather seems to augment its sensitivity to alkylating mutagens as well as mutagens which probably cause frameshift mutations. Other tests for mutations and/or inherited tumor proneness using mouse germ cells can easily be combined with the H test, because the test animal does not have to be killed, thus reducing the cost of the test.

2-Acetylaminofluorene↗