Phenotype resembling Donnai-Barrow syndrome in a patient with 9qter;16qter unbalanced translocation

We describe a 3-year-old boy with complete agenesis of corpus callosum, developmental delay/mental retardation, anterior diaphragmatic hernia, Morgagni type, severe hypermetropia, and facial dysmorphism suggesting the diagnosis of Donnai-Barrow syndrome. Subtelomeric FISH analysis revealed a paternally-derived t(9;16) (q34.3;q24.3) translocation with partial 9q monosomy and partial 16q trisomy. As some facial features resemble the 9q emerging phenotype, we suggest the hypothesis that some patients with Donnai-Barrow syndrome might be abscribed to 9q terminal deletion.     

Construction of an internal RT-PCR standard control for the detection of human caliciviruses in stool

RT-PCR is the most sensitive assay for the detection of human caliciviruses (HuCV) in stool and environmental samples. However, false negative results are commonly obtained due to the presence of RT-PCR inhibitors. In order to exclude such false negative results, an internal control (IC) was developed for the assay by cloning a 319 nt sequence of the Norwalk virus (NV) polymerase containing a 156 nt cDNA insert. The RT-PCR assay was carried out using RNA derived from the constructed plasmid and a primer set previously described for calicivirus detection, resulting in a 475 nt product. Distinct bands of the internal control and the viral specific RT-PCR products (319 nt) were obtained when the internal control was added to the samples. Similar results were also obtained when both the control RNA and viral RNA were seeded into stool samples from asymptomatic volunteers, or when the internal control was included into positive samples. Since the primer set used in the assays can detect a wide range of strains in both norovirus and sapovirus genera, this internal control should have a broad application for the diagnosis of human caliciviruses diagnosis in both clinical and environmental samples.     

Increased lipid and protein oxidation and lowered anti-oxidant defenses in systemic lupus erythematosus are associated with severity of illness,autoimmunity, increased adhesion molecules,and Th1 and Th17 immune shift

This study investigated nitro-oxidative stress in patients with systemic lupus erythematosus (SLE) in association with disease activity, immune-inflammatory biomarkers, and adhesion molecules. Two-hundred-four patients with SLE and 256 healthy volunteers were enrolled in this case-control study, which measured nitro-oxidative stress biomarkers, including lipid peroxides (LOOH), advanced oxidation protein products (AOPPs), nitric oxide metabolites (NO_x), sulfhydryl (?SH) groups, products of deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) oxidative degradation, and total radical-trapping anti-oxidant parameter (TRAP). Also measured were anti-nuclear antibodies (ANAs), antibodies against double-stranded DNA (dsDNA), plasma levels of diverse cytokines, C-reactive protein, and adhesion molecules. LOOH (p < 0.001) and AOPP (p < 0.001) were significantly higher, while TRAP was significantly lower (p < 0.001) in SLE patients than in controls. AOPP and LOOH were significantly and positively associated with SLE disease activity index (SLEDAI) scores, anti-nuclear antibodies, and antibodies against double-stranded DNA (anti-dsDNA) levels, while TRAP was significantly and inversely correlated with SLEDAI, ANA, and dsDNA antibody levels. There were significant positive associations between AOPP and LOOH and immune-inflammatory markers, indicating T helper (Th)-17 and Th1 bias and Th1 + Th17/Th2 ratio (p = 0.002 and p = 0.001, respectively). AOPP and LOOH (positively) and TRAP (inversely) were associated with adhesion molecule expression. A model predicting SLE was computed showing that, using LOOH, AOPP, NO_x, adhesion molecules, and body mass index, 94.2% of the patients were correctly classified with a specificity of 91.5%. Increased nitro-oxidative stress takes part in the (auto)immune pathophysiology of SLE and modulates severity of illness and adhesion molecule expression.     

Cloning and expression of a truncated form of envelope glycoprotein D of Bovine herpesvirus type 5 in methylotrophic yeast Pichia pastoris

Meningoencephalitis caused by Bovine herpesvirus type 5 (BoHV-5) is responsible for heavy economic losses in the cattle industry. As in other Alphaherpesviruses, the envelope glycoprotein IV (gD), which mediates penetration into host cells, is one of the major candidate antigens for a recombinant vaccine, since it induces a strong and persistent immune response. The DNA coding for a truncated form of BoHV-5 gD (tgD) has been cloned into the Pichia pastoris expression vector pPICZαB to allow protein secretion into the medium. After induction with methanol, a 55 kDa protein was obtained. Enzyme deglycosylation with Endo H showed a smaller size band in SDS-PGAE, with 50 kDa, suggesting that tgD has N-linked oligosaccharides and that it is not hyperglycosylated. The 55 kDa protein was recognized by several polyclonal antibodies, including polyclonal antibody anti-tgD and polyclonal antibodies of different animal species immunized with BoHV-5 and BoHV-1. This is the first report of BoHV-5 gD expression in yeast. It was shown that the recombinant truncated form of BoHV-5 gD has antigenic and immunogenic properties similar to the native BoHV-5 gD. Expression of tgD as a secreted protein allows simple and inexpensive purification methods that can be used for further studies to evaluate its immunogenicity in cattle.     

Lymphoma stem cells: enough evidence to support their existence?

While leukemia-originating stem cells are critical in the initiation and maintenance of leukemias, the existence of similar cell populations that may generate B-cell lymphoma upon mutation remains uncertain. Here we propose that committed lymphoid progenitor/precursor cells with an active V-D-J recombination program are the initiating cells of follicular lymphoma and mantle cell lymphoma when targeted by immunoglobulin (IG)- gene translocations in the bone marrow. However, these pre-malignant lymphoma-initiating cells cannot drive complete malignant transformation, requiring additional cooperating mutations in specific stem-cell programs to be converted into the lymphoma-originating cells able to generate and sustain lymphoma development. Conversely, diffuse large B-cell lymphoma and sporadic Burkitt’s lymphoma derive from B lymphocytes that acquire translocations through IG-hyper-mutation or class-switching errors within the germinal center. Although secondary reprogramming mutations are generally required, some cells such as centroblasts or memory B cells that have certain stem cell-like features, or lymphocytes with MYC rearrangements that deregulate self-renewal pathways, may bypass this need and directly function as the lymphoma-originating cells. An alternative model supports an aberrant epigenetic modification of gene sets as the first occurring hit, which either leads to retaining stem-cell features in hematopoietic stem or progenitor cells, or reprograms stemness into more committed lymphocytes, followed by secondary chromosomal translocations that eventually drive lymphoma development. Isolation and characterization of the cells that are at the origin of the different B-cell non-Hodgkin’s lymphomas will provide critical insights into the disease pathogenesis and will represent a step towards the development of more effective therapies.     

Iatrogenic ureteral lesions and repair: a review for gynecologists

Ureter injuries are a well-known complication of gynecologic surgery and a frequent cause of medicolegal problems. Because there are no randomized, controlled trials and the available studies are small series and case reports, the evidence on which to base treatment is weak. We therefore reviewed the complete English-language literature of ureter repair since 1990. In total, 608 ureter injuries were reported. Although it is widely believed that for laceration or section the prognosis is affected by a delay in diagnosis, we could not find evidence to substantiate this. An obstruction requires stenting only. For a laceration, stenting with suturing was more effective than stenting only (p = .006). A ureter anastomosis was successful in over 94% of cases either by laparotomy or laparoscopy. In conclusion, the literature data are scanty and heterogeneous and do not permit solid conclusions. Evidence, however, is emerging that a laceration should be treated by stenting and suturing. A ureter anastomosis over a stent could become a valid option especially when performed by laparoscopy.     

A Nightly Bedtime Routine: Impact on Sleep in Young Children and Maternal Mood

Background:

Establishment of a consistent bedtime routine is often recommended to parents of young children, especially those with sleep difficulties. However, no studies have investigated the efficacy of such a routine independent of behavioral intervention. Thus, the purpose of this study was to examine the impact of a consistent bedtime routine on infant and toddler sleep, as well as maternal mood.

Methods:

405 mothers and their infant or toddler (ages 7-18 months, n = 206; ages 18-36 months, n = 199) participated in 2 age-specific 3-week studies. Families were randomly assigned to a routine or control group. The first week of the study served as a baseline during which the mothers were instructed to follow their child''s usual bedtime routine. In the second and third weeks, mothers in the routine group were instructed to conduct a specific bedtime routine, while the control group continued their child''s usual routine. All mothers completed the Brief Infant Sleep Questionnaire (BISQ) on a weekly basis and a daily sleep diary, as well as completed the Profile of Mood States (POMS).

Results:

The bedtime routine resulted in significant reductions in problematic sleep behaviors for infants and toddlers. Significant improvements were seen in latency to sleep onset and in number/duration of night wakings, P < 0.001. Sleep continuity increased and there was a significant decrease in the number of mothers who rated their child''s sleep as problematic. Maternal mood state also significantly improved. Control group sleep patterns and maternal mood did not significantly change over the 3-week study period.

Conclusion:

These results suggest that instituting a consistent nightly bedtime routine, in and of itself, is beneficial in improving multiple aspects of infant and toddler sleep, especially wakefulness after sleep onset and sleep continuity, as well as maternal mood.

Citation:

Mindell JA; Telofski LS; Wiegand B; Kurtz ES. A nightly bedtime routine: impact on sleep in young children and maternal mood. SLEEP 2009;32(5):599–606.     

Immunopathologic role of B lymphocytes in rheumatoid arthritis: rationale of B cell-directed therapy

Although the immunopathogenesis of rheumatoid arthritis (RA) remains unclear, recent advances have paved the way for new therapies, such as anti-cytokine and cell-directed therapies. Here, B cells have re-gained interest concerning the pathogenesis of a number of autoimmune diseases after observing that patients with RA and non-Hodgkin lymphoma, who received anti-CD20 therapy leading to B cell depletion, demonstrated remarkable improvements. The underlying modes of action appear to be related to B cell functions, such as deletion of memory B cells, interruption of immune activation, antigen-presentation and production of inflammatory cytokines. In many RA patients, synovial extrafollicular germinal centers develop, where B cells play an intimate role in local inflammation and the generation of memory B cells and plasma cells. These local processes lead to activation of the immune system and ultimately to joint destruction in RA. Recent data demonstrating the clinical value of B cell depletion in refractory RA patients substantiate the notion that B cells are important players in the pathogenesis of the disease. Future studies should clarify which functions are affected by B cell depletion, providing the promise of new avenues to patient-tailored therapies.