Structural preferences of beta-galactoside-reactive lectins on Actinomyces viscosus T14V and Actinomyces naeslundii WVU45.

Specificities of lectins on Actinomyces viscosus T14V and Actinomyces naeslundii WVU45 were compared by measuring the abilities of D-galactose, N-acetyl-D-galactosamine, 14 beta-D-galacto-oligosaccharides, and 2 beta-D-fuco-oligosaccharides to inhibit coaggregation between Streptococcus sanguis 34 and each actinomycete. Inhibition profiles were similar, but WVU45 was significantly more sensitive to several inhibitors. D-Galactose-beta(1 leads to 3)-N-acetyl-D-galactosamine glycosides were most potent.     

Fludarabine: a new agent with major activity against chronic lymphocytic leukemia

Fludarabine was used to treat 68 patients with previously treated chronic lymphocytic leukemia (CLL). Nine (13%) patients achieved a complete remission and 30 (44%) a partial remission. The response rates for Rai stages 0 to 2, 3, and 4 were 64%, 58%, and 50% respectively. Seventeen (43%) of the 40 Rai stage 1 to 3 patients and four (19%) of the Rai stage 4 patients returned to Rai stage 0. Survival was strongly correlated with the final Rai stage achieved. The survival of the 11 partial responders with residual disease consisting only of residual bone-marrow nodules was similar to the complete responders (36+ months) and superior to the other partial response patients (16 months). The response to fludarabine was rapid, with 36 (92%) of the 39 responders having achieved at least a partial response following the first three courses. Complete responses occurred in the blood, liver, spleen, and lymph nodes in 48% to 69% of the patients. Eradication of all disease in the bone marrow occurred in only 13% of the cases. Neutropenia and thrombocytopenia occurred in 56% and 25% of evaluable courses. Major infections occurred in 9% of evaluable courses and fevers of unknown origin or minor infections in 12% of courses respectively. Myelosuppression and infection were more common in patients with initial Rai stages 3 and 4 and in nonresponding patients. Other toxicity was mild. No CNS toxicity was noted.     

CD18 deficiency protects against multiple low-dose streptozotocin-induced diabetes

Leukocyte recruitment into pancreatic islets is believed to play an important pathophysiological role in autoimmune diabetes. Previous reports have suggested that several different adhesion molecules may be involved in leukocyte recruitment during autoimmune diabetes, including members of the leukocyte beta(2) integrins. Here we report that a gene-targeted deficiency of the beta(2) integrin, CD18, protects against multiple low-dose streptozotocin-induced autoimmune diabetes. CD18 null mice displayed lower blood glucose values throughout the study, with only 10% of these mice eventually developing diabetes compared to 95% in the control group. Importantly, the development of insulitis was markedly absent in the CD18 null mice, suggesting that members of this integrin subfamily predominately regulate leukocyte infiltration into pancreatic islets. This study demonstrates that the beta(2) integrins play a key pathophysiological role in the development of multiple low-dose streptozotocin-induced autoimmune diabetes.     

Myocardial Contractility in Premature Neonates With and Without Patent Ductus Arteriosus

Controversy exists as to whether a hemodynamically significant left-to-right shunt due to a patent ductus arteriosus (PDA) affects ventricular contractility. Load-dependent indices such as ejection fraction and shortening fraction have traditionally been used to assess contractility, but the relationship between the rate-corrected velocity of fiber shortening (MVCFc) and wall stress may be more suitable, as it is a preload-independent, afterload-adjusted method of assessing ventricular contractility. Age-related differences have been established for these variables in normal adults and children and it has been recommended for use in the premature neonate. The study was performed to assess left ventricular contractility in premature neonates with a significant left-to-right shunt due to a PDA. Using echocardiography, we measured the relationship of MVCFc to stress at peak systole (SPS) in two groups of premature infants. Group 1 consisted of 15 controls (680–1495 g, 25–32 weeks gestation), and Group 2 of 15 neonates with hemodynamically significant PDA (840–1635 g, 26–33 weeks gestation). In both groups, MVCFc was linearly and inversely related to SPS (p < 0.001). The regression equations were as follows: Group 1, MVCFc = –0.0153SPS + 1.70 (R² = 0.68); and Group 2, MVCF = – 0.019SPS + 1.89 (R² = 0.76). There was no significant difference in the relationship between the two groups, but their slopes were significantly steeper and had a higher Y-intercept than the relationship we previously reported for older children. This preliminary study establishes the normal MVCFc/SPS relationship in the premature neonate (25–33 weeks gestation) and suggests that premature infants function at a higher resting contractile state than older children. A hemodynamically significant PDA has no effect on contractility. These data will be useful in assessing left ventricular contractility in premature neonates with other types of ventricular loading and noncardiac stress.     

Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition

Background  

The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease.     

Parent–infant psychotherapy: a systematic review of the evidence for improving parental and infant mental health

Background: Parent–infant psychotherapy (PIP) is a psychodynamic intervention with parent–infant dyads, designed to address regulatory disturbances in infancy and problems in the parent–infant relationship.

Aims: This systematic review aimed to examine whether PIP is effective in improving the parent–infant relationship or other aspects of parent or infant functioning.

Methods: A systematic review was undertaken. Electronic databases were searched for randomised controlled trials in which participants had been allocated to a PIP intervention or control group/other treatment.

Results: Eight studies were identified that provided data comparing parent–infant psychotherapy with a no-treatment control group (four studies) or comparing PIP with other kinds of treatment (four studies). Meta-analyses indicated that parents who received PIP were more likely to have an infant who was rated as being securely attached to the parent after the intervention; however, there were no significant differences in studies comparing outcomes of PIP with another model of treatment.

Conclusions: Although PIP appears to be a promising method of improving infant attachment security, there is inconclusive evidence of its benefits in terms of other outcomes, and no evidence to show that it is more effective than other interventions for parents and infants. Many studies had limitations in their design or implementation, and findings must be interpreted with caution.     

Long-range DNase I hypersensitivity mapping reveals the imprinted Igf2r and Air promoters share cis-regulatory elements

Epigenetic mechanisms restrict the expression of imprinted genes to one parental allele in diploid cells. At the Igf2r/Air imprinted cluster on mouse chromosome 17, paternal-specific expression of the Air noncoding RNA has been shown to silence three genes in cis: Igf2r, Slc22a2, and Slc22a3. By an unbiased mapping of DNase I hypersensitive sites (DHS) in a 192-kb region flanking Igf2r and Air, we identified 21 DHS, of which nine mapped to evolutionarily conserved sequences. Based on the hypothesis that silencing effects of Air would be directed towards cis regulatory elements used to activate genes, DHS are potential key players in the control of imprinted expression. However, in this 192-kb region only the two DHS mapping to the Igf2r and Air promoters show parental specificity. The remaining 19 DHS were present on both parental alleles and, thus, have the potential to activate Igf2r on the maternal allele and Air on the paternal allele. The possibility that the Igf2r and Air promoters share the same cis-acting regulatory elements, albeit on opposite parental chromosomes, was supported by the similar expression profiles of Igf2r and Air in vivo. These results refine our understanding of the onset of imprinted silencing at this cluster and indicate the Air noncoding RNA may specifically target silencing to the Igf2r promoter.     

Computational Model of Device-Induced Thrombosis and Thromboembolism

A numerical model of thrombosis/thromboembolism (T/TE) is presented that predicts the progression of thrombus growth and thromboembolization in low-shear devices (hemodialyzers, oxygenators, etc.). Coupled convection–diffusion-reaction equations were solved to predict velocities, platelet agonist (ADP, thromboxane A2, and thrombin) concentrations, agonist-induced and shear-induced platelet activation, and platelet transport and adhesion to biomaterial surfaces and adherent platelets (hence, thrombus growth). Single-platelet and thrombus embolization were predicted from shear forces and surface adhesion strengths. Values for the platelet-biomaterial reaction constant and the platelet adhesion strength were measured in specific experiments, but all other parameter values were obtained from published sources. The model generated solutions for sequential time steps, while adjusting velocity patterns to accommodate growing surface thrombi.Heparinized human blood was perfused (0.75 ml/min) through 580 μm-ID polyethylene flow cells with flow contractions (280 μm-ID). Thrombus initiation, growth, and embolization were observed with videomicroscopy, while embolization was confirmed by light scattering, and platelet adhesion was determined by scanning electron microscopy.Numerical predictions and experimental observations were similar in indicating: 1) the same three thrombotic locations in the flow cell and the relative order of thrombus development in those locations, 2) equal thrombus growth rates on polyethylene and silicon rubber (in spite of differing overall T/TE), and 3) similar effects of flow rate (1.5 ml/min versus 0.75 ml/min) on platelet adhesion and thrombosis patterns.