Molecular epidemiologic evaluation of endocarditis due to Oerskovia turbata and CDC group A-3 associated with contaminated homograft valves

Oerskovia turbata is an unusual bacterial cause of endocarditis and septicemia in immunocompromised patients. In this study, we compared 12 isolates from a 1975 medical center cluster, 11 originally identified as O. turbata (four from the blood of a homograft aortic valve-associated endocarditis patient and seven from contaminated homograft valves) and one CDC group A-3 strain from the blood of a second endocarditis patient with fatal outcome, with eight control strains from unrelated locations. The control strains included type and reference strains of O. turbata, Cellulomonas hominis, and CDC group A-3. The four blood isolates from the first patient and six of the valve isolates shared identical biochemical, antimicrobial susceptibility, and BglI ribotype patterns that differed from the second patient's isolate and control strains. The blood isolate from the second patient and the remaining valve isolate shared a phenotypic and genotypic profile and were phenotypically identical to, but epidemiologically different from, the CDC group A-3 reference strain with the strain-specific enzyme. Also, these isolates differed from the type strain and the other reference strains of C. hominis and O. turbata. Our results indicate that the four blood isolates from the first patient and six of the homograft valve isolates represent a single clone of O. turbata associated with endocarditis. Additionally, our results indicate that the blood isolate from the second patient and one of the homograft valve isolates differ from O. turbata and C. hominis and represent a unique clone of CDC group A-3 associated with fatal endocarditis.     

Validation and advantages of FAWSETS perfusion measurements in skeletal muscle

This work discusses the strengths, limitations and validity of a novel arterial spin labeling technique when used specifically to measure perfusion in limb skeletal muscle. The technique, flow-driven arterial water stimulation with elimination of tissue signal (FAWSETS), offers several advantages over existing arterial spin labeling techniques. The primary goal of this study was to determine the perfusion signal response to changes in net hind limb flow that were independently verifiable. The range of perfusate flow was relevant to skeletal muscle during mild to moderate exercise. Localized, single voxel measurements were acquired from a 5 mm-thick slice in the isolated perfused rat hind limb at variable net flow rates. The results show that the perfusion signal is linearly proportional to net hind limb flow with a correlation coefficient of 0.974 (p = 0.0013). FAWSETS is especially well suited for studies of skeletal muscle perfusion, where it eliminates the need to compensate for magnetization transfer and arterial transit time effects. A conceptual discussion of the basic principles underlying these advantages is presented.     

Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase C gamma 2 that specifically increases external Ca2+ entry

The identification of specific genetic loci that contribute to inflammatory and autoimmune diseases has proved difficult due to the contribution of multiple interacting genes, the inherent genetic heterogeneity present in human populations, and a lack of new mouse mutants. By using N-ethyl-N-nitrosourea (ENU) mutagenesis to discover new immune regulators, we identified a point mutation in the murine phospholipase Cg2 (Plcg2) gene that leads to severe spontaneous inflammation and autoimmunity. The disease is composed of an autoimmune component mediated by autoantibody immune complexes and B and T cell independent inflammation. The underlying mechanism is a gain-of-function mutation in Plcg2, which leads to hyperreactive external calcium entry in B cells and expansion of innate inflammatory cells. This mutant identifies Plcg2 as a key regulator in an autoimmune and inflammatory disease mediated by B cells and non-B, non-T haematopoietic cells and emphasizes that by distinct genetic modulation, a single point mutation can lead to a complex immunological phenotype.     

Histomorphometrical and comparative analysis of three muscles of buffalo (Bubalus bubalis L.)

Three muscles were analyzed, Longissimus dorsi, Semimembranosus and Caput longum Tricipitis brachii taken from nine cow buffaloes, by examining the histochemical and morphometrical characteristics of different muscle fibres types and their distribution inside the examined muscles. Cross sectional area, perimeter, maximum and minimum diameter of about 200 fibres were measured for each muscle, and fast-twitch glycolytic fibres (FG), fast-twitch oxidative-glycolytic fibres (FOG), slow-twitch oxidative fibres (SO) were histochemically differentiated. The data have been elaborated with the SPSS software. The variance analysis indicates that there are not significant differences about dimensions between FG and FOG fibres, while the average values of transversal section area and perimeter are greater than the oxidative fibres in all examined muscles. The Semimembranosus muscle in comparison to the Longissimus dorsi and to the Caput longum Tricipitis brachii muscles has muscle fibres with the smallest value of transversal section area and perimeter. The balanced distribution and intense myofibrillar adenosine triphosphatose and succinic dehydrogenase activities of the three fibres types in Caput longum Tricipitis brachii muscle can be justified by the function performed by this muscle which, together with the other heads of the Triceps brachii acts essentially as extensor of the forearm in fact, differences in the dimensions of the different fibre types inside the three examined muscles have been underlined; this fact can be justified for every muscle performs different motor functions.     

Effects of endothelin-1 on epithelial ion transport in human airways

Endothelin-1 (ET-1) exerts many biological effects in airways, including bronchoconstriction, airway mucus secretion, cell proliferation, and inflammation. We investigated the effect of ET-1 on Na absorption and Cl secretion in human bronchial epithelial cells. Addition of 10(-7) M ET-1 had no effect on the inhibition of the short circuit current (Isc) induced by amiloride, a Na channel blocker. Addition of 10(-7) M ET-1 to the apical bath in the presence of amiloride increased Isc in cultured human bronchial epithelial cells studied in Ussing chambers. No effect was observed when ET-1 was added to basolateral bath, indicating that the involved ET-1 receptors are likely present only in the apical membrane of the cells. Use of Cl-free solutions and bumetanide reduced the ET-1-induced increases in Isc, indicating that ET-1 stimulates Cl secretion. The ET-1-induced increase in Isc was prevented by exposure to the ETB receptor antagonist BQ-788 but not to the ETA receptor antagonist BQ-123. ET-1 did not raise intracellular Ca levels, but increased the intracellular concentration of cAMP. These findings indicate that ET-1 is a Cl secretagogue in human airways and acts presumably through apically located ETB receptors and activation of the cAMP pathway.     

PDGF enhancement of IL-1 receptor levels in smooth muscle cells involves induction of an attachment-regulated,heparan sulfate binding site (IL-1RIII)

This study shows that increase in IL-1 receptor levels by platelet derived growth factor (PDGF) involves an enhancement of a matrix-dependent, low-affinity receptor that constitutes a heparan sulfate. Fibronectin attachment caused pronounced alterations in IL-1 receptor function in smooth muscle cells, involving a pronounced increase in cell surface binding from an average of 2,000 up to approximately 8,000 receptors/cell and an increase in affinity (K(a)) of the type I receptor from 1.8 +/- 0.9 x 10(9) to 3.7 +/- 0.5 x 10(9) M(-1). PDGF stimulation similarly enhanced the level of cell surface binding by between 30% and 100%, with, in general, less effect on cells plated on fibronectin. Further, PDGF had a pronounced effect on the type I receptor affinity in the absence of matrix attachment, increasing the K(a) from 1.77 +/- 0.93 x 10(9) to 5.1 +/- 2.1 x 10(9) M(-1). Scatchard analyses revealed that PDGF, similarly to fibronectin attachment, caused enhancement of a second low-affinity binding site. Antibody blocking showed that approximately 50% of the attachment-induced increase was independent of type I receptor binding. Further, a similar fraction of the cell surface interaction was blocked by soluble heparan sulfate and dependent on cell binding to the heparan binding site. Cross-linking demonstrated that, in addition to the type I receptor, IL-1 bound to a second high molecular weight complex of 300 kd, induced by fibronectin attachment as well as by PDGF in the absence of matrix. Biochemical analyses demonstrated that this second site constitutes a heparan sulfate, which directly interacted with the type I receptor after recruitment to the complex, and which bound up to 50% and 25% of the ligand after fibronectin attachment and PDGF stimulation, respectively. The data show that PDGF induces an attachment-regulated low-affinity IL-1 binding site in smooth muscle cells, constituting a heparan sulfate. Correlation of the recruitment of this component to the IL-1 receptor complex with structural regulation of receptor function and enhancement of IL-1-mediated responses suggests that this is a significant mechanism in PDGF augmentation of local inflammatory responses during vessel wall pathogenesis.     

Basal cytokines profile in metastatic renal cell carcinoma patients treated with subcutaneous IL-2-based therapy compared with that of healthy donors

Background and purpose  

Metastatic renal cell carcinoma (MRCC) has a poor prognosis with a median overall survival of about one year. Since only a minority of patients experienced therapeutic benefit to current treatments, several studies have attempted to identify factors that may have an impact on response and survival. Cytokines play a crucial role in the host's immune response by regulating the development and function of a lot of biological compartments. Nevertheless, available data on basal cytokine levels in MRCC are very few and no clear profile of serum cytokines has been identified yet in these patients population. Thus, determining the levels of cytokines in MRCC could not only help in understanding the biological mechanisms of the tumor growth, but also in evaluating if different cytokine profiles are correlated with particular clinical behaviors.     

Cellular life histories and bow tie biology.

Considering the life-long influences of fetal growth biology, it is of interest to further elucidate the nature of the fetal growth process itself. Previous analyses of longitudinal fetal ultrasound data led to the hypothesis that hypoxia signals were important aspects of normal growth biology and directed attention to the place of oxygen as a basic nutrient. From the perspective of the cell, both hypoxia and lack of energy substrate trigger a common adaptive pathway through their effects on ATP availability. Comparative data from animal studies and cell culture provide evidence for an integrated energy/oxygen signaling system that acts redundantly and hierarchically with cellular differentiation programs, providing opportunities for developmental flexibility in response to variable ecologic or environmental challenge. The multinodal and interactive design of the fetal growth process suggests that it follows what has been described as the "bow tie" model of metabolism, with implications for robust and inventive approaches to cell, organ, and whole organism construction.     

Evaluating the impact of a service fee on patient compliance

This paper addresses an evaluation of an administrative decision to change the manner in which services were paid for at a Student Health Center (SHC). The impact of the change in payment was observed through monitoring the number of scheduled appointments at the SHC which the patient failed to attend, reschedule, or cancel. The impact was assessed through a comparison of the weekly no-show rates from the year prior to the change in payment practices through the year following the change. A time-series statistical package was used to analyze the no-show data. Collateral measures on the number of students attending the university, staff opinions, and usage of the SHC by different student groups were collected. Evaluations of the impact of administrative decisions on health-related behavior were discussed, in addition to a discussion of the usefulness of time-series models for this type of evaluation.