Effects of bariatric surgery on telomere length and T-cell aging.

BACKGROUND: Obesity adversely affects health and is associated with subclinical systemic inflammation and features of accelerated aging, including the T-cell immune system. The presence of metabolic syndrome (MetS) may accelerate, while bariatric surgery might reverse these phenomena. To examine the effects of MetS and bariatric surgery on T-cell aging, we measured relative telomere length (RTL) and T-cell differentiation status in obese patients before and after bariatric surgery. METHODS: WHO II/III classified obese patients scheduled for bariatric surgery were included: 41 without MetS and 67 with MetS. RTL and T-cell differentiation status were measured in circulating CD4+ and CD8+ T cells via flow cytometry. T-cell characteristics were compared between patients with and without MetS prior to and at 3, 6, and 12 months after surgery considering effects of age, cytomegalovirus-serostatus, and weight loss. RESULTS: Thymic output, represented by numbers of CD31-expressing naive T cells, showed an age-related decline in patients with MetS. MetS significantly enhanced CD8+ T-cell differentiation. Patients with MetS had significant lower CD4+ RTL than patients without MetS. Within the first 6 months after bariatric surgery, RTL increased in CD4+ T cells after which it decreased at month 12. A decline in both thymic output and more differentiated T cells was seen following bariatric surgery, more pronounced in the MetS group and showing an association with percentage of body weight loss. CONCLUSIONS: In obese patients, MetS results in attrition of RTL and accelerated T-cell differentiation. Bariatric surgery temporarily reverses these effects. These data suggest that MetS is a risk factor for accelerated aging of T cells and that MetS should be a more prominent factor in the decision making for eligibility for bariatric surgery.

Uremia-Associated Premature Aging of T Cells Does Not Predict Infectious Complications After Renal Transplantation.

Patients with end-stage renal disease have prematurely aged T cell systems. We tested whether T cell aging parameters were associated with the risk of infections after renal transplantation (RTx). We studied 188 patients over 1 year. Peripheral T cells were analyzed before and at 3 and 6 mo after RTx for frequency of recent thymic emigrants, relative telomere length and differentiation status. These parameters were related to the occurrence of opportunistic and serious infections. Overall, 84 patients developed an infection. In this group, 50 developed an opportunistic infection and 53 developed a serious infection. T cell aging parameters assessed before RTx were not associated with infection risk. The memory T cells showed a decrease within the first 3 mo in both groups (p < 0.001). The CD4(+) memory T cells increased between 3 and 6 mo within the infection group (p = 0.015). The number of CD8(+) memory T cells increased in both groups (p < 0.001) but reached baseline levels only in the infection group. In the infection group, the CD8(+) CD28(null) T cell percentage increased between 3 and 6 mo (p = 0.024), tending to be higher than at baseline (p = 0.061). These differences in post-RTx dynamics resulted from infections. Parameters of uremia-associated premature aging of peripheral T cells do not predict posttransplant infections.

Primary Cytomegalovirus Infection Significantly Impacts Circulating T Cells in Kidney Transplant Recipients.

Cytomegalovirus (CMV) infection profoundly affects the T cell compartment and is associated with alterations in T cell aging parameters and generation of cytotoxic CD4(+) CD28null T cells. Hence, the effect of a primary CMV infection post-kidney transplantation (KT) on the peripheral T cell compartment was examined. As aging parameters, we determined the T cell differentiation status, T cell receptor excision circle (TREC) content, CD31(+) naïve T cell numbers and relative telomere length (RTL) pre-KT and 12 months post-KT. CMV-seronegative KT recipients, receiving a kidney from a CMV-seropositive donor (D+/R-) were compared to D+/R+ KT recipients. Eleven out of the 22 D+/R- KT recipients had CMV viremia post-KT. They developed CMV-specific CD4(+) and CD8(+) T cells and their T cell compartment shifted towards a more differentiated memory phenotype with expansion of CD4(+) CD28null and CD8(+) CD28null cells. One year post-KT, the CD8(+) T cell count was almost doubled compared to nonviremic D+/R- and D+/R+ KT recipients. In addition, the RTL of the CD8(+) T cell was significantly lower and both the TREC content and CD31(+) naïve T cell numbers significantly decreased. Moreover, primary CMV infection was associated with a negative impact on glomerular filtration rate. In conclusion, primary CMV infection has a substantial impact on the number and phenotype of peripheral T cells and may negatively affect renal allograft function.

Cytomegalovirus contributes partly to uraemia-associated premature immunological ageing of the T cell compartment.

Cytomegalovirus (CMV) infection has been implicated in accelerated T cell ageing. End-stage renal disease (ESRD) patients have a severely immunologically aged T cell compartment but also a high prevalence of CMV infection. We investigated whether CMV infection contributes to T cell ageing in ESRD patients. We determined the thymic output by the T cell receptor excision circle (TREC) content and percentage of CD31+ naïve T cells. The proliferative history of the T cell compartment by determination of the relative telomere length (RTL) and the T cell differentiation status was determined by immunophenotyping. It appeared that CMV infection did not affect thymic output but reduced RTL of CD8+ T cells in ESRD patients. Moreover, increased T cell differentiation was observed with higher percentages of CD57+ and CD28null CD4+ and CD8+ memory T cells. These CD28null T cells had significantly shorter telomeres compared to CD28+ T cells. Therefore we concluded that CMV infection does not affect the decreased thymic output but increases T cell differentiation as observed in ESRD-related premature T cell ageing.

Electrical transport properties of single undoped and n-type doped InN nanowires.

Electrical transport properties of undoped and n-type doped InN nanowires grown by molecular beam epitaxy were studied by current-voltage and back-gate field-effect transistor measurements. The current-voltage characteristics show ohmic behavior in the temperature range between 4 and 300 K. Down to about 120 K a linear decrease in resistance with temperature is observed. The investigation of a large number of nanowires revealed for undoped as well as doped wires an approximately linear relation between the normalized conductance and diameter for wires with a diameter below 100 nm. This shows that the main conduction takes place in the tubular surface accumulation layer of the wires. In contrast, for doped wires with a diameter larger than 100 nm a quadratic dependence of conduction on the diameter was found, which is attributed to bulk conductance as the main contribution. The successful doping of the wires is confirmed by an enhanced conduction and by the results of the back-gate field-effect transistor measurements.

Raman scattering study of GaN nanostructures obtained by bottom-up and top-down approaches.

GaN nanocolumnar structures were grown by plasma-assisted molecular beam epitaxy (PAMBE) and also fabricated by electron cyclotron resonance reactive ion etching (ECR-RIE) of a compact GaN film parallel to the [111] direction of the Si(111) substrates. Scanning electron microscopy shows that the nanocolumns fabricated by PAMBE have a length of about 300-500 nm with diameters ranging from 20 to 150 nm while nanowhiskers formed by RIE have diameters of 40-80 nm and a height between 1.4 and 1.7 µm. A comparative study of the vibrational spectrum (including optical and interface phonons) of the nanostructures using conventional macro-Raman and micro-Raman scattering as well as surface-enhanced Raman scattering is presented.

Signaling mechanism of the netrin-1 receptor DCC in axon guidance.

DCC (Deleted in Colorectal Cancer) is a single-pass transmembrane protein that belongs to the immunoglobulin superfamily. It was originally identified as a prognostic tumor marker and then subsequently found to be a receptor for netrin-1. DCC plays a key role in axon guidance and also in a number of other important cellular processes. This review describes the current progress of the structural biology of DCC with an emphasis on how DCC is involved in the dual functionality of netrin-1 as a chemo-attractant as well as a repellent in axon guidance, referred to as bi-functionality. A perspective about other DCC ligands and the signaling mechanism of the cytoplasmic tail of DCC is also recapitulated.

Research on the impact of forest stand structure on atmospheric deposition.

Dry and wet deposition onto thirty forest stands in relation to stand structure is studied by sampling throughfall and bulk precipitation. Nine measurement sites are situated in Pseudotsuga menziesii stands, ten in Pinus sylvestris and eleven in Quercus robur stands. All stands are situated within a radius of 1.2 km to assure a more or less equal air pollution load. In each stand, detailed forest structure inventories are made to determine aerodynamic roughness, collecting efficiency and surface area parameters. Measurements to data cover a four month period (April-July 1990). First results show relatively high throughfall deposition in Pseudotsuga menziesii stands. Lowest throughfall fluxes are recorded for Quercus robur and intermediate values for Pinus sylvestris stands. There are indications of a relatively strong canopy exchange in Quercus robur stands during the measurement period. Many results from forest stand structure inventories are not available yet. However, a strong relation is observed between throughfall deposition in Pseudotsuga menziesii stands and total crown volume.

Integration of a blood pressure controller and an infusion toolbox system using client-server technology.

This paper shortly describes an Infusion Toolbox and a blood pressure (BP) control application. It explains how we applied an agent model and client-server technology to integrate them. We show that by using this framework and object oriented technologies the necessary changes to the existing applications are reduced. Many elements of the tested original systems could be re-used, which enhances safe development.

Acoustic charge transport in GaN nanowires.

We present acoustic charge transport in GaN nanowires (GaN NWs). The GaN NWs were grown by molecular beam epitaxy (MBE) on silicon(111) substrates. The nanowires were removed from the silicon substrate, aligned using surface acoustic waves (SAWs) on the piezoelectric substrate LiNbO(3) and finally contacted by electron beam lithography. Then, a SAW was used to create an acoustoelectric current in the GaN NWs which was detected as a function of radio-frequency (RF) wave frequency and its power. The presented method and our experimental findings open up a route towards new acoustic charge transport nanostructure devices in a wide bandgap material such as GaN.

Investigation on localized states in GaN nanowires.

GaN nanowires with diameters ranging between 50 and 500 nm were investigated by electrical and photoinduced current techniques to determine the influence of their size on the opto-electronic behavior of nanodevices. The conductivity, photoconductivity, and persistent photoconductivity behavior of GaN nanowires are observed to strongly depend on the wire diameter. In particular, by spectral photoconductivity measurements, three main sub-band-gap optoelectronic transitions were detected, ascribed to the localized states giving rise to the characteristic blue, green, and yellow bands of GaN. Photoconductivity with below-band-gap excitation varies orders of magnitude with the wire diameter, similarly to that observed for near-band-edge excitation. Moreover, yellow-band-related signal shows a superlinear behavior with respect to the band-edge signal, offering new information for the modeling of the carrier recombination mechanism along the nanowires. The photoconductivity results agree well with a model which takes into account a uniform distribution of the localized states inside the wire and their direct recombination with the electrons in the conduction band.

Indirect immunofluorescence test for detection of IgM antibodies to cytomegalovirus.

A technique for the detection of IgM antibodies to cytomegalovirus (CMV) by immunofluorescence was developed. In order to prevent interference by rheumatoid factor in the sera, IgG was removed by prior immunoabsorption with antiserum to gamma Fc. Sera from 63 patients with a rise in titer of antibody to CMV, indicated by complement fixation, were IgM-positive, but yielded negative results on the Paul-Bunnell-Davidsohn test for infectious mononucleosis. Convalescent-phase serum samples from 20 patients with a seroconversion to herpes simplex virus and from 20 patients with a seroconversion to varicella-zoster virus also had no IgM antibodies to CMV. Sera from six of 10 patients with infectious mononucleosis and two of 100 normal blood donors were positive for IgM antibodies to CMV. In 38 of 63 patients, the diagnosis of CMV infection could be made several weeks earlier by the immunofluorescence test than by the complement-fixation test. IgM antibodies to CMV persisted for more than two months after onset of symptoms of the infection.

Clinical evaluation of an automatic blood pressure controller during cardiac surgery.

OBJECTIVE: During surgery, computers can be of great use to support the anesthesiologist in providing task automation. In this paper we describe a closed loop blood pressure controller and show the results of its clinical evaluation. METHODS: The controller is based on a simple and robust Proportional-Integral controller and a supervising, rule based, expert system. Adaptive control is necessary because the sensitivity of the patients to sodium nitroprusside varies over a wide range. Thirty-three clinical tests during cardiac surgery, including the cardiopulmonary bypass phase, were performed. RESULTS: On average the controller was in automatic mode for 90.6 +/- 9.6% of the time. The performance during automatic control showed the mean arterial pressure to be within 10 mmHg of the setpoint for 71.4 +/- 15.5% of the time. The average absolute distance to the setpoint was 8.1 +/- 7.2 mmHg. CONCLUSIONS: The overall performance of the controller was noted as very satisfactory by the anesthesiologists.

Orthogonal-field-alternation gel electrophoresis banding patterns of DNA from yeasts.

Chromosomal DNAs from various yeast species were separated by orthogonal-field-alternation gel electrophoresis (OFAGE). To this end we developed a spheroplasting and lysis method to obtain intact DNA from both ascomycetous and basidiomycetous yeasts. The OFAGE banding patterns of 22 ascomycetous and four basidiomycetous yeast strains were compared. The strains represented species from the genera: Brettanomyces, Candida, Cryptococcus, Filobasidiella, Geotrichum, Hansenula, Kluyveromyces, Pachysolen, Pichia, Rhodosporidium, Rhodotorula, Saccharomyces, Saccharomycodes, Saccharomycopsis, Schizosaccharomyces and Zygosaccharomyces. Variations occurred in the number of bands and their positions in the gel, not only among strains of different genera but also among species from the same genus and even between varieties of the same species. The ascomycetous yeasts, with the exception of Saccharomyces cerevisiae, only showed one to five bands of DNA larger than 1000 kilobase pairs (kb) in general none smaller. The patterns of the four basidiomycetous yeasts revealed also a few large DNA bands but in addition one to six bands ranging in size from 500 to 1000 kb, with the exception of a single smaller chromosome in Rhodotorula mucilaginosa. From the OFAGE banding patterns of strains studied here it appears that in Sacch. cerevisiae the partitioning of DNA over chromosomes is unique. But rather than the large number of chromosomes, the presence of four chromosomes with less than 500 kb of DNA is characteristic for Sacch. cerevisiae.

On the enzymatic activation of NADH.

Atomic (1 A) resolution x-ray structures of horse liver alcohol dehydrogenase in complex with NADH revealed the formation of an adduct in the active site between a metal-bound water and NADH. Furthermore, a pronounced distortion of the pyridine ring of NADH was observed. A series of quantum chemical calculations on the water-nicotinamide adduct showed that the puckering of the pyridine ring in the crystal structures can only be reproduced when the water is considered a hydroxide ion. These observations provide fundamental insight into the enzymatic activation of NADH for hydride transfer.

Structural basis for substrate specificity differences of horse liver alcohol dehydrogenase isozymes.

A structure determination in combination with a kinetic study of the steroid converting isozyme of horse liver alcohol dehydrogenase, SS-ADH, is presented. Kinetic parameters for the substrates, 5beta-androstane-3beta,17beta-ol, 5beta-androstane-17beta-ol-3-one, ethanol, and various secondary alcohols and the corresponding ketones are compared for the SS- and EE-isozymes which differ by nine amino acid substitutions and one deletion. Differences in substrate specificity and stereoselectivity are explained on the basis of individual kinetic rate constants for the underlying ordered bi-bi mechanism. SS-ADH was crystallized in complex with 3alpha,7alpha,12alpha-trihydroxy-5beta-cholan -24-acid (cholic acid) and NAD(+), but microspectrophotometric analysis of single crystals proved it to be a mixed complex containing 60-70% NAD(+) and 30-40% NADH. The crystals belong to the space group P2(1) with cell dimensions a = 55.0 A, b = 73.2 A, c = 92.5 A, and beta = 102.5 degrees. A 98% complete data set to 1.54-A resolution was collected at 100 K using synchrotron radiation. The structure was solved by the molecular replacement method utilizing EE-ADH as the search model. The major structural difference between the isozymes is a widening of the substrate channel. The largest shifts in C(alpha) carbon positions (about 5 A) are observed in the loop region, in which a deletion of Asp115 is found in the SS isozyme. SS-ADH easily accommodates cholic acid, whereas steroid substrates of similar bulkiness would not fit into the EE-ADH substrate site. In the ternary complex with NAD(+)/NADH, we find that the carboxyl group of cholic acid ligates to the active site zinc ion, which probably contributes to the strong binding in the ternary NAD(+) complex.

Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule.

The structural basis of the interaction between the CD4 coreceptor and a class II major histocompatibility complex (MHC) is described. The crystal structure of a complex containing the human CD4 N-terminal two-domain fragment and the murine I-A(k) class II MHC molecule with associated peptide (pMHCII) shows that only the "top corner" of the CD4 molecule directly contacts pMHCII. The CD4 Phe-43 side chain extends into a hydrophobic concavity formed by MHC residues from both alpha 2 and beta 2 domains. A ternary model of the CD4-pMHCII-T-cell receptor (TCR) reveals that the complex appears V-shaped with the membrane-proximal pMHCII at the apex. This configuration excludes a direct TCR-CD4 interaction and suggests how TCR and CD4 signaling is coordinated around the antigenic pMHCII complex. Human CD4 binds to HIV gp120 in a manner strikingly similar to the way in which CD4 interacts with pMHCII. Additional contacts between gp120 and CD4 give the CD4-gp120 complex a greater affinity. Thus, ligation of the viral envelope glycoprotein to CD4 occludes the pMHCII-binding site on CD4, contributing to immunodeficiency.