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Biomedical subjects

R Lang

Publications and source records attributed to R Lang.

At least 55 records · Page 3Linked to original sources

Circulating, Mycobacterium tuberculosis-specific lymphocytes from PPD skin test-negative patients with tuberculosis do not secrete interferon-gamma (IFN-gamma) and lack the cutaneous lymphocyte antigen skin-selective homing receptor.

Individuals with a negative intradermal reaction to tuberculin PPD have long been described in the Mycobacterium tuberculosis exposed, immune-competent population. Here, we studied PPD-specific blood T lymphocytes from these subjects for phenotypic markers relevant to skin migration, including the expression of the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen (CLA). Out of 82 patients with active tuberculosis we identified four subjects who were repeatedly PPD skin test-negative. CD4 T lymphocytes specific to mycobacterial antigens were derived from these individuals, which (i) proliferated in vitro to M. tuberculosis antigens comparably to those from PPD+ patients; (ii) secreted comparable amounts of IL-2 but lower amounts of IFN-gamma; (iii) were confined within the CLA-negative T cell subset. We conclude that the negative tuberculin reaction in a small subset of patients exposed to mycobacteria is associated with impaired production of IFN-gamma by circulating PPD-specific T cells that are lacking CLA expression. On this basis in vitro proliferation to PPD can discriminate bona fide non-responders from infected patients with a deficit in the margination of M. tuberculosis-specific T lymphocytes.

Adult↗

CpG-oligodeoxynucleotides enhance T-cell receptor-triggered interferon-gamma production and up-regulation of CD69 via induction of antigen-presenting cell-derived interferon type I and interleukin-12.

Bacterial cytidine-phosphate-guanosine (CpG-DNA) activates antigen-presenting cells (APC) and drives T helper 1 (Th1)-polarized immune responses in the mouse. Claims have been made that CpG-DNA costimulates murine T cells. We examined the direct and indirect effects of CpG-oligodeoxynucleotides (CpG-ODN) on human T-cell activation. CpG-ODN failed to costimulate purified human T cells activated with alpha-CD3 or alpha-T-cell receptor (TCR)alphabeta antibodies. In contrast, CpG-ODN sequence-specifically caused increased expression of CD69 on CD4 and CD8 T cells when peripheral blood mononuclear cells (PBMC) were stimulated via alpha-CD3. CpG-ODN and alpha-CD3 stimulation synergized to induce interferon-gamma (IFN-gamma) in T cells and natural killer (NK) cells, as shown by intracellular fluorescence-activated cell sorter (FACS) staining. These effects of CpG-ODN on human T cells were caused by the release of IFN type I (IFN-I) and interleukin-12 (IL-12) from PBMC. Enhancement of CD69 expression on alpha-CD3-triggered T cells could be reproduced in a coculture transwell system of purified T cells and PBMC, was inhibited by neutralizing antibodies to IFN-I and could be mimicked by adding exogenous IFN-I. Furthermore, neutralization of either IFN-I or IL-12 diminished, and in combination abolished, IFN-gamma production. These findings show that CpG-ODN potentiate TCR-triggered activation of human T cells in an APC-dependent manner.

Adjuvants, Immunologic↗

Comparison of in vitro fracture strength of metallic and tooth-coloured posts and cores.

In root-treated anterior teeth a better aesthetic can be achieved by using translucent and tooth-coloured post and core restorations instead of traditional metal post systems. The aim of this in vitro study was to compare the fracture strength of tooth-coloured ceramic and fibre-reinforced posts as well as titanium posts with clinically proven gold alloy posts as a control. Two all-ceramic, one gold alloy and three combined post restoration systems (titanium and ceramic, respectively, fibre-reinforced posts with composite core) were each applied to upper incisors and after thermal cycling and mechanical loading (TCML) the fracture strength was determined. The variant providing the most reliable fracture strength values and the experimental fibre-reinforced composite (FRC) posts were - in combination with adhesively luted crowns - used to determine the fracture strength of the restoration after thermal cycling and mechanical loading. The median fracture strength of the luted posts and cores fluctuated between 114 and 546 N. Posts with composite cores demonstrate a higher fracture strength in comparison to the all-ceramic and gold alloy systems. Typical failure of metal systems was marked by loosening of the bonding and pulling out of the post in contrast to fracture of the ceramic posts. After the application of the crowns the ceramic system with composite core provided a fracture strength of 338 N and the FRC system a fracture strength of 228 N. Regarding fracture strength, the ceramic posts with composite cores are an alternative to commonly used gold posts and cores. A standardized technical manufacture of FRC posts and cores would provide better fracture strength results of this new dental material. Post and core restorations with tooth-coloured, translucent material offer an improved aesthetic especially in anterior restorations. Because of the high fracture strength prefabricated ceramic posts in combination with composite cores should prove their clinical applicability.

Aluminum Silicates↗

Normal values of regional left ventricular endocardial motion: multicenter color kinesis study.

Our goal was to establish normal values for quantitative color kinesis indexes of left ventricular (LV) wall motion over a wide range of ages, which are required for objective diagnosis of regional systolic and diastolic dysfunction. Color-encoded images were obtained in 194 normal subjects (95 males, 99 females, age 2 mo to 79 yr) in four standard views. Quantitative indexes of magnitude and timing of systolic and diastolic function were studied for age- and gender-related differences. Normal limits of all ejection and filling indexes were in a narrow range (< or =25% of the mean), with no major gender-related differences. Despite invariable ejection fractions, both peak filling and ejection rates decreased with age (30 and 20%, correspondingly) with a concomitant increase in mean filling and ejection times, resulting in five- and twofold increases in the late to early filling and ejection ratios, correspondingly. Diastolic asynchrony increased with age (from 4.7 +/- 2.0 to 6.4 +/- 3.2 from the 2nd to 7th decade). The normal values of color kinesis indexes should allow objective detection of regional LV systolic and diastolic dysfunction.

Adolescent↗

KCNA10: a novel ion channel functionally related to both voltage-gated potassium and CNG cation channels.

Our laboratory previously cloned a novel rabbit gene (Kcn1), expressed in kidney, heart, and aorta, and predicted to encode a protein with 58% amino acid identity with the K channel Shaker Kv1.3 (Yao X et al. Proc Natl Acad Sci USA 92: 11711-11715, 1995). Because Kcn1 did not express well (peak current in Xenopus laevis oocytes of 0.3 microA at +60 mV), the human homolog (KCNA10) was isolated, and its expression was optimized in oocytes. KCNA10 mediates voltage-gated K(+) currents that exhibit minimal steady-state inactivation. Ensemble currents of 5-10 microA at +40 mV were consistently recorded from injected oocytes. Channels are closed at the holding potential of -80 mV but are progressively activated by depolarizations more positive than -30 mV, with half-activation at +3.5 +/- 2.5 mV. The channel displays an unusual inhibitor profile because, in addition to being blocked by classical K channel blockers (barium tetraethylammonium and 4-aminopyridine), it is also sensitive to inhibitors of cyclic nucleotide-gated (CNG) cation channels (verapamil and pimozide). Tail-current analysis shows a reversal potential shift of 47 mV/decade change in K concentration, indicating a K-to-Na selectivity ratio of at least 15:1. The phorbol ester phorbol 12-myristate 13-acetate, an activator of protein kinase C, inhibited whole cell current by 42%. Analysis of single-channel currents reveals a conductance of approximately 11 pS. We conclude KCNA10 is a novel human voltage-gated K channel with features common to both K-selective and CNG cation channels. Given its distribution in renal blood vessels and heart, we speculate that KCNA10 may be involved in regulating the tone of renal vascular smooth muscle and may also participate in the cardiac action potential.

Animals↗

In vitro repair of all-ceramic and fibre-reinforced composite crowns.

Shear bond strength between fibre reinforced composite and all-ceramic frameworks and veneering/repair composites was investigated after different surface treatments for evaluating the possibility of a repair. Then, 24 crowns were adhesively luted on human teeth and artificially aged. Repair quality was characterized by a loading to fracture test, where undamaged crowns were compared to repaired crowns. To simulate repeated damage, aging and repair, the procedure was performed three times for each crown. A combined silicate-silane treatment of the fibre-reinforced composite frameworks and the hydrofluoric acid etching of the ceramic showed good repair qualities and a sufficient fracture strength for clinical application.

Analysis of Variance↗

Introduction to the application of capillary gas chromatography of performance-enhancing drugs in doping control.

Performance-enhancing drugs banned by antidoping rules are detected in doping control preferably by hyphenated chromatographic techniques, capillary gas chromatography in particular. Based on the prohibited classes of substances and on the general aspects of sample collection and preparation, a survey is given about the usual procedures of screening, identification and confirmation of the most important doping agents: stimulants, narcotics, anabolics, diuretics, beta-blockers. In addition to gas chromatography itself, the application of various MS techniques doping is outlined.

Adrenergic beta-Antagonists↗

Guanosine-rich oligodeoxynucleotides induce proliferation of macrophage progenitors in cultures of murine bone marrow cells.

Widely used to specifically inhibit gene expression, synthetic oligodeoxynucleotides (ODN) can exert a plethora of non-antisense effects. Immunostimulation by CpG-ODN has attracted particular attention. ODN rich in the nucleotide guanosine (G-rich ODN) constitute another type of sequences displaying non-antisense-mediated effects. We have examined the effects of CpG- and G-rich ODN on primary mouse bone marrow cells (BMC) in vitro. CpG-ODN induced rapid proliferation of B cells and production of IL-6 and IL-12p40. However, when tested in agar colony assays, CpG-ODN failed to promote the formation of colonies. In marked contrast, G-rich non-CpG-ODN led to sustained proliferation of macrophage-like cells without inducing cytokines or hemopoietic growth factors. Unlike CpG-ODN, G-rich ODN effectively induced the formation of macrophage colonies in agar assays, indicating a direct action on progenitor cells. Electrophoretic mobility shift assays revealed specific binding of G-rich ODN to a non-nuclear protein. The ability of a panel of ODN to compete for binding correlated with their potential to induce proliferation of macrophage-like cells from primary mouse BMC. As such, these data reveal a so far unrecognized potential of G-rich ODN to signal directly outgrowth of macrophage progenitors from BMC.

Agar↗

[Documentation of the effects of child cap pistols].

The study presents an analysis of 20 cases of acute acoustic trauma caused by toy pistols. The problem generally involves boys within the age range from 6 to 11 years. Half of the incidents involved attacks with toy pistols used as weapons. Auditory damage appeared in two types, each of which had a notch in the audiogram at the frequency range between 10 and 14 kHz. In children, a shot close to one ear can damage both ears. Great differences in the severity of tinnitus were apparent. The most severe cases of tinnitus were observed in the children with no or minor permanent auditory damage. Children experiencing long periods of uninterrupted tinnitus suffer significantly. This is not only detrimental to family life, but also to the performance of the children at school. The total expenses of treatment for these 20 cases were estimated to be approximately 80,000 DM (40,000 Euro).

Audiometry, Pure-Tone↗

Human gastrin: a Helicobacter pylori--specific growth factor.

BACKGROUND & AIMS: Helicobacter pylori resides within the gastric mucosa, a niche hostile to other microorganisms. Human gastrin levels are elevated after infection and return to normal after eradication. The aim of this study was to test the direct effect of gastrin on the growth of H. pylori. METHODS: H. pylori and control bacteria were grown with gastrin or control peptides and growth rate was determined. (125)I-labeled gastrin was used to determine uptake. RESULTS: Human gastrin stimulated H. pylori growth in a specific, dose-dependent manner. Gastrin shortened the lag time, increased growth rate in the logarithmic phase, and increased final bacterial concentration at the stationary phase. These effects were shown over a wide concentration range, including physiological luminal and serum levels. Labeled gastrin uptake was inhibited by unlabeled gastrin. Controls consisting of cholecystokinin and pentagastrin inhibited gastrin uptake but did not stimulate growth. In contrast, somatostatin and epidermal growth factor had no effect on either gastrin uptake or bacterial growth. These results suggest a structurally restricted, receptor-mediated, gastrin-specific effect. CONCLUSIONS: Human gastrin is a specific growth factor for H. pylori and may have a role in the adaptation of H. pylori to its unique habitat.

Campylobacter jejuni↗

Sustained hemodynamic effects of an infusion of nesiritide (human b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial. Natrecor Study Group.

OBJECTIVES: The goal of this study was to further define the role of nesiritide (human b-type natriuretic peptide) in the therapy of decompensated heart failure (HF) by assessing the hemodynamic effects of three doses (0.015, 0.03 and 0.06 microg/kg/min) administered by continuous intravenous (IV) infusion over 24 h as compared with placebo. BACKGROUND: Previous studies have shown beneficial hemodynamic, neurohormonal and renal effects of bolus dose and 6-h infusion administration of nesiritide in HF patients. Longer term safety and efficacy have not been studied. METHODS: This randomized, double-blind, placebo-controlled multicenter trial enrolled subjects with symptomatic HF and systolic dysfunction (left ventricular ejection fraction < or =35%). Central hemodynamics were assessed at baseline, during a 24-h IV infusion and for 4 h postinfusion. RESULTS: One hundred three subjects with New York Heart Association class II (6%), III (61%) or IV (33%) HF were enrolled. Nesiritide produced significant reductions in pulmonary wedge pressure (27% to 39% decrease by 6 h), mean right atrial pressure and systemic vascular resistance, along with significant increases in cardiac index and stroke volume index, with no significant effect on heart rate. Beneficial effects were evident at 1 h and were sustained throughout the 24-h infusion. CONCLUSIONS: The rapid and sustained beneficial hemodynamic effects of nesiritide observed in this study support its use as a first-line IV therapy for patients with symptomatic decompensated HF.

Atrial Natriuretic Factor↗

The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy.

A method is described for measuring optical properties and deriving chromophore concentrations from diffuse reflection measurements at the surface of a turbid medium. The method uses a diffusion approximation model for the diffuse reflectance, in combination with models for the absorption and scattering coefficients. An optical fibre-based set-up, capable of measuring nine spectra from 400 to 1050 nm simultaneously, is used to test the method experimentally. Results of the analyses of phantom and in vivo measurements are presented. These demonstrate that in the wavelength range from 600 to 900 nm, tissue scattering can be described as a simple power dependence of the wavelength and that the tissue absorption can be accurately described by the addition of water, oxy- and deoxyhaemoglobin absorption.

Humans↗

Distinct regulatory elements govern Fgf4 gene expression in the mouse blastocyst, myotomes, and developing limb.

Embryonic development requires a complex program of events which are directed by a number of signaling molecules whose expression must be rigorously regulated. We previously showed that expression of Fgf4, which plays an important role in postimplantation development and growth and patterning of the limb, is regulated in EC cells by the synergistic interaction of Sox2 and Oct-3 with the Fgf4 EC cell-specific enhancer. To verify whether this mechanism was also operating in vivo, and to identify new elements controlling Fgf4 gene expression in distinct developmental stages, we have analyzed the expression of LacZ reporter plasmids containing different fragments of the Fgf4 gene in transgenic mouse embryos. Utilizing these transgenic constructs we have been able to recapitulate, for the most part, Fgf4 gene expression during embryonic development. We show here that most of the cis-acting regulatory elements determining Fgf4 embryonic expression are located in conserved regions within the 3' UTR of the gene. The EC cell-specific enhancer is required to drive gene expression in the ICM of the blastocyst, and its activity requires the Sox and Oct-proteins binding sites. We were also able to identify specific and distinct enhancer elements that govern postimplantation expression in the somitic myotomes and the limb bud AER. The myotome-specific elements contain binding sites for bHLH myogenic regulatory factors, which appear to be essential for myotome expression. Finally, we present evidence that the very restricted pattern of expression of Fgf4 transcripts in the AER results from the combined action of positive and negative regulatory elements located 3' of the Fgf4 coding sequences. Thus the Fgf4 gene relies on multiple and distinct regulatory elements to achieve stage- and tissue-specific embryonic expression.

Animals↗

Colour stability of provisional crown and bridge restoration materials.

OBJECTIVE: In an in vitro study to determine the colour stability of provisional restoration materials, the PMMA synthetics Trimm and Cronsin and the bis-acrylic composites Protemp Garant, Protemp Garant NF, Protemp II and Provipont DC were investigated. MATERIALS AND METHODS: The colour changes of the cylindrical untreated samples were measured in comparison with samples after 24 and 72 hours of artificial ageing in a Suntest CPS+ UV ageing device using the Minolta CM 3500d spectrophotometer according to the CIE-L*a*b* system. RESULTS: Trimm (light), Cronsin (brown, yellow and universal), Provipont DC (yellow) and Protemp Garant NF (extra light) displayed the greatest discoloration with values > or = 4-21 delta E, where discoloration toward yellow could be discerned. The remaining materials showed lower luminance reflectance values of < or = 1-4 delta E, and therefore greater colour stability. CONCLUSIONS: Because of their colour stability the materials Cronsin (grey), Protemp Garant (yellow), Protemp II (light), Protemp Garant NF (yellow, light and extra light) could also be used as long-term interim prosthetics.

Analysis of Variance↗

Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s.

T helper cells type 1 (Th1s) that produce interferon-gamma predominantly mediate cellular immune responses and are involved in the development of chronic inflammatory conditions, whereas Th2s which produce large amounts of IL-4 and IL-5 upregulate IgE production and are prominent in the pathogenesis of allergic diseases. The precise factors determining whether Th1- or Th2-mediated immune responses preferentially occur at a peripheral site of antigen exposure are largely unknown. Chemokines, a superfamily of polypeptide mediators, are a key component of the leukocyte recruitment process. Here we report that among four CXC (CXCR1-4) and five CC (CCR1-5) chemokine receptors analyzed, CXCR3 and CCR5 are preferentially expressed in human Th1s. In contrast, Th2s preferentially express CCR4 and, to a lesser extent, CCR3. In agreement with the differential chemokine receptor expression, Th1s and Th2s selectively migrate in response to the corresponding chemokines. The differential expression of chemokine receptors may dictate, to a large extent, the migration and tissue homing of Th1s and Th2s. It may also determine different susceptibility of Th1s and Th2s to human immunodeficiency virus strains using different fusion coreceptors.

Cell Movement↗

Inhibition of IL-12 production by 1,25-dihydroxyvitamin D3. Involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene.

Interleukin 12 (IL-12), produced by myelomonocytic cells, plays a pivotal role in the development of T helper 1 (Th1) cells, which are involved in the pathogenesis of chronic inflammatory autoimmune disorders. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] inhibits IL-12 production by activated macrophages and dendritic cells, thus providing a novel interpretation to its immunosuppressive properties. 1,25(OH)2D3 significantly inhibits mRNA expression for both IL-12 p35 and p40 subunits acting at the transcriptional level. The effect of 1,25(OH)2D3 on p40 promoter activation was analyzed by cotransfecting monocytic RAW264.7 cells with p40 promoter/reporter constructs and expression vectors for vitamin D3 receptor (VDR) and/or retinoid X receptor (RXRalpha). We observed transcriptional repression of the p40 gene by 1,25(OH)2D3, which required coexpression of VDR with RXR and an intact VDR DNA-binding domain. The repressive effect maps to a region in the p40 promoter containing a binding site for NF-kappaB (p40-kappaB). Deletion of the p40-kappaB site abrogates part of the inhibitory effect on the p40 promoter, confirming the functional relevance of this site. Activation of monocytic THP-1 cells in the presence of 1,25(OH)2D3 results in reduced binding to the p40-kappaB site. Thus, 1,25(OH)2D3 may negatively regulate IL-12 production by downregulation of NF-kappaB activation and binding to the p40-kappaB sequence.

Animals↗

[Toy cap pistols and their effect on hearing].

In order to understand the repeated occurrences of auditory impairments caused by toy pistols, an analysis of the circumstances involved was performed at Justus-Liebig University of Giessen. The acoustic impact of toy pistols on the ear was determined with a special measuring system for impulse noise. Results were compared with the acoustic impacts of the G3 common rifle of the German military on the ear of the soldier. It was apparent that all of the five randomly selected types of toy pistols were much louder than the military rifle, if fired close to the ear. The current standard of the European Union related to the safety of toys (EN 71-1) tolerates peaks of impulse noise from toy pistols that are actually illegal for workplaces without auditory protection. Measurements showed that the toy pistols tested were even louder than that tolerated by the EU standard. Problems related to acute acoustic trauma caused by these toys are discussed using recent examples. In order to prevent such injuries, we suggest limiting the loudness of the "worst case" instead of using unrealistic measurements.

Auditory Fatigue↗