Association of Streptococcus bovis Bacteremia with Bowel Disease

We reviewed the medical records of 19 patients who had Streptococcus bovis bacteremia. Eight patients had diverticulosis, four had benign adenomatous colonic polyps, and three had adenocarcinomas of the gastrointestinal tract. Laboratory workers and clinicians should be aware of the association of S. bovis bacteremia and gastrointestinal disease.     

Immunity induced shortly after DNA vaccination of rainbow trout against rhabdoviruses protects against heterologous virus but not against bacterial pathogens.

It was recently reported that DNA vaccination of rainbow trout fingerlings against viral hemorrhagic septicaemia virus (VHSV) induced protection within 8 days after intramuscular injection of plasmid DNA. In order to analyse the specificity of this early immunity, fish were vaccinated with plasmid DNA encoding the VHSV or the infectious haematopoietic necrosis virus (IHNV) glycoprotein genes and later challenged with homologous or heterologous pathogens. Challenge experiments revealed that immunity established shortly after vaccination was cross-protective between the two viral pathogens whereas no increased survival was found upon challenge with bacterial pathogens. Within two months after vaccination, the cross-protection disappeared while the specific immunity to homologous virus remained high. The early immunity induced by the DNA vaccines thus appeared to involve short-lived non-specific anti-viral defence mechanisms.     

Human herpesvirus type 6 reactivation after haematopoietic stem cell transplantation

Human herpesvirus type 6 (HHV6) is known to reactivate after hematopoetic stem cell transplantation (HSCT) and has been suggested to be associated with increased mortality and severe clinical manifestations, including graft versus host disease (GvHD). The exact etiological role of HHV6 reactivation in increased morbidity and mortality after HSCT remains unclear. This review will focus on the current available evidence of HHV6 reactivation after HSCT and its immuno-modulatory capacities, with particular emphasis on the severe complication GvHD. At present, no effective specific antiviral treatment for HHV6 reactivation has been identified. The currently available antiviral agents are outlined, as well as possible future strategies for the treatment of HHV6 reactivation. Non-toxic, specific treatment or prevention of HHV6 reactivation might improve the safety and efficacy of the HSCT procedure.     

Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next‐generation sequencing

Leukodystrophies are a heterogeneous group of heritable disorders characterized by abnormal brain white matter signal on magnetic resonance imaging (MRI) and primary involvement of the cellular components of myelin. Previous estimates suggest the incidence of leukodystrophies as a whole to be 1 in 7,000 individuals, however the frequency of specific diagnoses relative to others has not been described. Next generation sequencing approaches offer the opportunity to redefine our understanding of the relative frequency of different leukodystrophies. We assessed the relative frequency of all 30 leukodystrophies (associated with 55 genes) in more than 49,000 exomes. We identified a relatively high frequency of disorders previously thought of as very rare, including Aicardi Goutières Syndrome, TUBB4A‐related leukodystrophy, Peroxisomal biogenesis disorders, POLR3‐related Leukodystrophy, Vanishing White Matter, and Pelizaeus‐Merzbacher Disease. Despite the relative frequency of these conditions, carrier‐screening laboratories regularly test only 20 of the 55 leukodystrophy‐related genes, and do not test at all, or test only one or a few, genes for some of the higher frequency disorders. Relative frequency of leukodystrophies previously considered very rare suggests these disorders may benefit from expanded carrier screening.     

Application of inter-simple sequence repeat PCR to mouse models: assessment of genetic alterations in carcinogenesis

Genomic instability is believed to play a significant role in cancer development by facilitating tumor progression and tumor heterogeneity. Inter-simple sequence repeat (inter-SSR) PCR has been proved to be a fast and reproducible technique for quantitation of genomic instability (amplifications, deletions, translocations, and insertions) in human sporadic tumors. However, the use of inter-SSR PCR in animal models of cancer has never been described. This new technique has been adapted in our laboratory for the analysis of spontaneous and induced mouse tumors. We established the best PCR conditions for each microsatellite-anchored primer and critically evaluated the reproducibility of the band patterns. We also studied the variation of the fingerprints between and within various inbred mouse strains, including wild-derived lines. Tumor-specific alterations were detected as gains, losses, or intensity changes in bands when compared with matched normal DNA. We quantitated the extent of alterations by dividing the number of altered bands in the tumor by the total number of bands in normal DNA (instability index). By means of inter-SSR PCR, we successfully analyzed genomic alterations in various mouse tumors, including spontaneous thymic lymphomas developed in Msh2 knockout mice as well as chemically induced squamous cell carcinomas and thymic lymphomas. Instability index values ranged between 0 and 9%, the highest levels observed in N-methyl-N-nitrosourea-induced thymic lymphomas generated in Trp53 (p53) nullizygote (-/-) mice. We report here, for the first time, the use of inter-SSR PCR to detect somatic mutations in mouse tumoral DNA, including laser-capture microdissected, methanol-fixed tissues. These PCR-based fingerprints provide a novel approach to assessing the number and onset of mutational events in mouse tumors and will help to understand better the mechanisms of carcinogenesis in mouse models.     

Genetic basis for remating inDrosophila melanogaster. III. Correlated responses to selection for female remating speed

Two natural populations ofDrosophila melanogaster selected for fast and slow female remating (Gromko and Newport,Behav. Genet.18: 621–632, 1988) were analyzed for correlated responses to selection. Several of the correlated responses differed between the lines derived from the two different source populations. In particular, the degree to which female receptivity to remating was dependent on the number of sperm in storage ceptivity to remating was dependent on the number of sperm in storage remained high in one pair of fast and slow selected lines but not in the other. In the line which retained sperm dependence (JEFFERS), fast and slow remating was achieved by changes in the threshold at which remating occurred. In the other line (COMP) changes in the temporal pattern of sperm use were seen. Thus both the level of the receptivity threshold and the existence of a sperm effect appeared to be selectable features of this species. Mated female attractiveness and receptivity were shown to be genetically distinct from virgin female attractiveness and receptivity. Effects of the genotype of the female on copulation duration were found.This work was supported by NSF Grants 82-01183 and 84-18934.     

Extinction responding by septal and normal rats following acquisition under four schedules of reinforcement

Extinction responding of animals with septal lesions was compared to that of normal animals following acquisition training under either DRL, FI, VI or FR reinforcement schedules (Part 1). During both acquisition and extinction, septals bar pressed more than normals. However, regardless of response levels, a given schedule changed behavior in the same direction for both septals and normals. Thus, if a given schedule led to a decrease in bar pressing by normals, it also led to a decrease by septals, although the absolute level of responding at which this occurred might be different for the two groups. Similarly, if a schedule led to an increase in responding by normals, it also led to an increase by septals. In Part 2 of the experiment operant levels of septals were not found to be different from those of normals, and noncontingent food delivery generated no more nor less bar pressing in septals than in normals. It was proposed that the septal area may be of importance in the initiation of behavior which competes with the required or reinforced response.     

Effects of overexpansion on stents' recoil, symmetry/asymmetry, and neointimal hyperplasia in aortas of hypercholesterolemic rabbits.

BACKGROUND: It is not known whether overexpansion modifies stent recoil, symmetric distribution of struts, and neointimal hyperplasia. OBJECTIVES: The objectives were (a) to evaluate whether stent overexpansion modifies the geometric configuration of the stent in the arterial wall, (b) to determine the relationship between overexpansion and stent recoil, and (c) to evaluate the relationship between the distribution of struts and neointimal hyperplasia. METHODS: Twenty tubular stainless steel 316L stents (3.0 and 3.5 mm in diameter) were implanted at 20 and 10 atm, respectively, in the abdominal aorta of New Zealand rabbits fed a hypercholesterolemic diet (1% cholesterol). Sham operations were also performed in seven animals. Eight weeks after implantation or sham operation, an intravascular ultrasound (IVUS) study was performed to measure stent recoil and aid in stent classification (symmetric or asymmetric) according to strut distribution. The degree of injury and neointimal hyperplasia were also evaluated in hematoxylin-eosin stained sections. RESULTS: The symmetry/asymmetry of stents assessed by IVUS, as well as the neointimal hyperplasia, was similar in both groups. Stent recoil was significantly greater in the 3.0-mm stent (overexpanded) group (0.28+/-0.02 mm), as compared with stent recoil in the 3.5-mm stent group (0.10+/-0.01 mm, P<.05). The neointimal hyperplasia in histological slices, independent of the implant technique, was predominantly in zones with higher strut concentration as compared with zones with fewer struts. CONCLUSIONS: Stent overexpansion enhanced stent recoil and did not modify symmetric and asymmetric strut distribution. Neointimal hyperplasia was not modified by the implant technique. Interestingly, significant hyperplasia was observed in locations with greater strut concentration, independent of overexpansion.     

Immunoglobulin M antibody responses to Mycobacterium ulcerans allow discrimination between cases of active Buruli ulcer disease and matched family controls in areas where the disease is endemic

Buruli ulcer disease (BUD) is an emerging disease caused by Mycobacterium ulcerans. In the present study we have characterized the serological reactivities of sera from volunteer case patients with laboratory-confirmed BUD and controls living in three different regions of Ghana where the disease is endemic to determine if serology may be useful for disease confirmation. Our results showed highly reactive immunoglobulin G (IgG) responses among patients with laboratory-confirmed disease, healthy control family members of the case patients, and sera from patients with tuberculosis from areas where BUD is not endemic. These responses were represented by reactivities to multiple protein bands found in the M. ulcerans culture filtrate (CF). In contrast, patient IgM antibody responses to the M. ulcerans CF (MUCF) proteins were more distinct than those of healthy family members living in the same village. A total of 84.8% (56 of 66) of the BUD patients exhibited strong IgM antibody responses against MUCF proteins (30, 43 and 70 to 80 kDa), whereas only 4.5% (3 of 66) of the family controls exhibited such responses. The sensitivity of the total IgM response for the patients was 84.8% (95% confidence interval [CI], 74.3 to 91.6%), and the specificity determined with sera from family controls was 95.5% (95% CI, 87.5 to 98.4%). These studies suggest that the IgM responses of patients with BUD will be helpful in the identification and production of the M. ulcerans recombinant antigens required for the development of a sensitive and specific serological assay for the confirmation of active BUD.