Kinetics of modification of the mitochondrial succinate-ubiquinone reductase by 5,5''-dithiobis-(2-nitro-benzoic acid)

In the present study, we examined the effect of the thromboxane/prostaglandin endoperoxide analogue U46619 on proliferation and hypertrophy in cultured rat vascular smooth muscle cells and the roles of protein kinase C and transforming growth factor-beta (TGF-beta) in the mediation of the hypertrophic response to U46619. Since an increase in basic fibroblast growth factor (bFGF) was previously shown to mediate the hypertrophic response to U46619, we also assessed the relationship between bFGF and TGF-beta in the expression of U46619 actions. U46619 increased [35S]methionine incorporation into protein and protein content of vascular smooth muscle cells but had no effect on cell number. A role for TGF-beta was supported by the following observations: (1) exogenous human TGF-beta 1 increased protein synthesis; (2) antibody to TGF-beta blocked both TGF-beta- and U46619-induced increases in protein content; (3) U46619 increased active and total TGF-beta bioactivities; and (4) the actions of U46619 on protein content and TGF-beta bioactivity were blocked by the thromboxane/prostaglandin endoperoxide receptor antagonist SQ 29,548. Previous observations had demonstrated a role for bFGF in the expression of U46619 actions on protein synthesis. Results of the present study suggest that TGF-beta and bFGF interact in mediating the protein synthetic response to U46619. First, the concentration of exogenous TGF-beta (10 pmol/L) alone required to produce a protein synthetic response equivalent to that induced by U46619 was much higher than the concentration of endogenous active TGF-beta that accumulated in the media in response to U46619 (0.7 pmol/L). Second, bFGF (20 ng/mL) increased total TGF-beta bioactivity and stimulated protein synthesis. The hyper-trophic response to bFGF was blocked by anti-TGF-beta. The ability of U46619 and bFGF to increase protein synthesis and protein content in vascular smooth muscle cells was associated with TGF-beta-induced suppression of proliferation, as evidenced by the ability of antibody to TGF-beta to enhance U46619- and bFGF-induced increases in [3H]thymidine incorporation into DNA. Results of the present study also supported a role for protein kinase C in the expression of U46619 and bFGF actions. U46619 increased protein kinase C activity in the particulate fraction of vascular smooth muscle cells. Moreover, the protein kinase C inhibitors GF109203X and staurosporine blocked U46619- and bFGF-induced increases in protein synthesis as well as active and total TGF-beta bioactivities. By contrast, the protein kinase C inhibitors did not prevent the increases in protein synthesis induced by exogenous TGF-beta. The results demonstrate that thromboxane/prostaglandin endoperoxide signals increased TGF-beta bioactivity via protein kinase C. Increases in both bFGF and TGF-beta are required for an optimal hypertrophic response to U46619. The hypertrophic response to TGF-beta occurs through a protein kinase C-independent pathway.     

Properties of whole saliva and dental plaque in relation to 40-month consumption of chewing gums containing xylitol, sorbitol of sucrose

The concern with nursing research in the future work of nurse graduates. Expectations from the viewpoint of the nurse researcher. Keeping in mind the concerns which occupy nurse researchers now and in the future, expectations are raised of the graduates of degree programmes in nursing science which are now also being established in the Federal Republic of Germany. This takes into account the structurally determined areas of self determined action in new fields of professional practice. Nurse graduates will be seen as "change agents" in their future areas of work and will have three essential aspects of involvement with nursing research: 1. they themselves will conduct research 2. they will receive, put into practice and transmit results of nursing research 3. they will initiate and commission nursing research projects. According to the broad topics of nursing research, requirements for nurses to act as professionals in their new working fields are formulated referring to the given structural conditions in Germany.     

Tyrosine administration prevents hypoxia-induced decrements in learning and memory

Exposure to hypobaric hypoxia rapidly produces decrements in learning and memory. Tyrosine, a neurotransmitter precursor, has beneficial behavioral effects when administered to animals and humans exposed to various acute stressors. To determine whether tyrosine would protect rats from the adverse effects of hypobaric hypoxia on spatial reference and working memory, it was administered to 27 male Fischer 344 rats tested in the Morris water maze. Rats were tested starting at 2 and 6 h of an 8 h exposure to a simulated altitude of 5950 m (19,500 ft) or sea level. Tyrosine or placebo was administered 1/2 h prior to each testing session (400 mg/kg, IP). Altitude exposure significantly increased working memory escape latency; treatment with tyrosine reversed this decrement. There was no effect of altitude or tyrosine on reference memory. There were also no treatment-related differences in performance when animals were tested the next day at sea level. The beneficial effects of tyrosine on working memory performance may be due to a direct effect of tyrosine on memory, alleviation of a hypoxia-induced retardation of learning, or to other central or peripheral effects of this dietary catecholamine precursor.     

Experimental and numerical investigation of the 3D SPECT photon detection kernel for non-uniform attenuating media

Experimental tests for non-uniform attenuating media are performed to validate theoretical expressions for the photon detection kernel, obtained from a recently proposed analytical theory of photon propagation and detection for SPECT. The theoretical multi-dimensional integral expressions for the photon detection kernel, which are computed numerically, describe the probability that a photon emitted from a given source voxel will trigger detection of a photon at a particular projection pixel. The experiments were performed using a cylindrical water-filled phantom with large cylindrical air-filled inserts to simulate inhomogeneity of the medium. A point-like, a short thin cylindrical and a large cylindrical radiation source of 99Tcm were placed at various positions within the phantom. The values numerically calculated from the theoretical kernel expression are in very good agreement with the experimentally measured data. The significance of Compton-scattered photons in planar image formation is discussed and highlighted by these results. Using both experimental measurements and the calculated values obtained from the theory, the kernel's size is investigated. This is done by determining the square N x N pixel neighbourhood of the gamma camera that must be connected to a particular radiation source voxel to account for a specific fraction of all counts recorded at all camera pixels. It is shown that the kernel's size is primarily dependent upon the source position and the properties of the attenuating medium through Compton scattering events, with 3D depth-dependent collimator resolution playing an important but secondary role, at least for imaging situations involving parallel hole collimation. By considering small point-like sources within a non-uniform elliptical phantom, approximating the human thorax, it is demonstrated that on average a 12 cm x 12 cm area of the camera plane is required to collect 85% of the total count recorded. This is a significantly larger connectivity than the 3 cm x 3 cm area required if scattering contributions are ignored and only the 3D depth-dependent collimator resolution is considered.     

New taxane diterpenoids from the roots of Taxus mairei

OBJECTIVE: We tested the hypothesis that nitric oxide synthesis by the kidney is increased in children with primary nephrotic syndrome. METHODS: We examined the urinary excretion of nitrite, a stable metabolite of nitric oxide, using the Griess reaction, in children with nephrotic syndrome. RESULTS: In comparison with healthy children, patients with minimal change nephrotic syndrome had increased urinary nitrite excretion regardless of whether the disease was in relapse or remission (p < 0.025). In contrast, urinary nitrite excretion was similar in control subjects and patients with focal segmental glomerulosclerosis or IgA nephropathy. CONCLUSION: These findings indicate that measurement of urinary nitrite excretion may be a useful test to help discriminate between minimal change nephrotic syndrome and focal segmental glomerulosclerosis in children with idiopathic nephrotic syndrome.     

Feasibility of estimating glomerular filtration rate in children using single-sample adult technique

This work was undertaken to verify whether a single-sample adult technique, when applied using body surface-corrected plasma concentration, can be used in place of specific pediatric method to estimate 51Cr-EDTA renal clearance in children. METHODS: In a series of 90 children (aged 0.1 to 15 yr). 51Cr-EDTA renal clearance was calculated using for different approaches. The first approach used specific pediatric single-sample methods; three techniques were chosen and they all used 120-min plasma concentration. The second approach used the same three specific pediatric methods, but they were applied using 120-min plasma concentration prescaled for 1.73 m2 body surface area. The third approach used single-sample methods designed for adults; three methods were again chosen. They all used 240-min plasma concentration. The fourth approach used the same adults algorithms, but they were applied using 240-min plasma concentration prescaled for 1.73 m2 body surface area. RESULTS: Clearances calculated using the three specific pediatric methods were all closely cross-correlated regardless of whether or not the plasma concentration was prescaled. The use of classical adult methods produced in some cases obviously erroneous clearance values. Improvements were observed when the same adult methods were applied using prescaled plasma concentration. Nonetheless, the clearance values obtained only fairly correlated with those obtained using specific pediatric methods. CONCLUSION: The single-sample adult technique using plasma concentration prescaled for 1.73 m2 body surface area cannot be used in place of a specific pediatric single-sample method to estimate 51Cr-EDTA renal clearance in children.     

Laryngeal Kaposi's sarcoma in patients with AIDS

Over a period of 10 years 17 human immunodeficiency virus(HIV)-infected patients with laryngeal Kaposi's sarcoma were seen and treated at University College London Hospitals. All patients had advanced HIV disease. Their presentation was with symptoms of upper airway obstruction in the majority of cases and the diagnosis was made by fibreoptic examination of the larynx. Biopsy was associated with brisk haemorrhage in one patient, who required a temporary tracheostomy, and was not performed in the other 16 cases. The commonest site of laryngeal involvement was the supraglottis in 11 patients, with glottic lesions noted in eight patients: subglottic lesions were seen in only three. Treatment of laryngeal Kaposi's sarcoma was, in general, conservative, five patients received low dose radiotherapy to the larynx and 10 were treated with systemic chemotherapy for disseminated Kaposi's sarcoma. Laryngeal Kaposi's sarcoma did not contribute to patient mortality.     

Haemonchus contortus glycoproteins contain N-linked oligosaccharides with novel highly fucosylated core structures

Structural studies on the N-linked oligosaccharides of Haemonchus contortus, an economically important nematode that parasitizes domestic ruminants, have revealed core fucosylation of a type not previously observed in any eukaryotic glycoprotein. Mass spectrometric analyses were performed on detergent extracts of homogenized adult H. contortus and on purified H11, a glycoprotein isolated from intestinal brush borders which has been previously shown to be an effective vaccine antigen. The major N-linked glycans identified in the present study have up to three fucose residues attached to their chitobiose cores. The fucoses are found at the 3- and/or 6-positions of the proximal GlcNAc and at the 3-position of the distal GlcNAc. The latter substitution is unique in N-glycans. Most anti-H11 monoclonal antibodies are known to recognize carbohydrate epitopes, and it is possible that the newly discovered multifucosylated core structures are highly immunogenic in this glycoprotein.     

2-Azetidinone cholesterol absorption inhibitors: structure-activity relationships on the heterocyclic nucleus

A series of azetidinone cholesterol absorption inhibitors related to SCH 48461 ((-)-6) has been prepared, and compounds were evaluated for their ability to inhibit hepatic cholesteryl ester formation in a cholesterol-fed hamster model. Although originally designed as acyl CoA: cholesterol acyltransferase (ACAT) inhibitors, comparison of in vivo potency with in vitro activity in a microsomal ACAT assay indicates no correlation between activity in these two models. The molecular mechanism by which these compounds inhibit cholesterol absorption is unknown. Despite this limitation, examination of the in vivo activity of a range of compounds has revealed clear structure-activity relationships consistent with a well-defined molecular target. The details of these structure-activity relationships and their implications on the nature of the putative pharmacophore are discussed.