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R Lang

Publications and source records attributed to R Lang.

At least 19 recordsLinked to original sources
PubMed2003

Nutritional management of rheumatoid arthritis: a review of the evidence.

Rheumatoid arthritis (RA) is a debilitating disease and is associated with increased risk of cardiovascular disease and osteoporosis. Poor nutrient status in RA patients has been reported and some drug therapies, such as nonsteroidal anti-inflammatory drugs (NSAIDs), prescribed to alleviate RA symptoms, may increase the requirement for some nutrients and reduce their absorption. This paper reviews the scientific evidence for the role of diet and nutrient supplementation in the management of RA, by alleviating symptoms, decreasing progression of the disease or by reducing the reliance on, or combating the side-effects of, NSAIDs. Supplementation with long-chain n-3 polyunsaturated fatty acids (PUFA) consistently demonstrates an improvement in symptoms and a reduction in NSAID usage. Evidence relating to other fatty acids, antioxidants, zinc, iron, folate, other B vitamins, calcium, vitamin D and fluoride are also considered. The present evidence suggests that RA patients should consume a balanced diet rich in long-chain n-3 PUFA and antioxidants. More randomized long-term studies are needed to provide evidence for the benefits of specific nutritional supplementation and to determine optimum intake, particularly for n-3 PUFA and antioxidants.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

In vitro study of fracture strength and marginal adaptation of polyethylene-fibre-reinforced-composite versus glass-fibre-reinforced-composite fixed partial dentures.

This in vitro study was carried out in order to estimate the clinical usability of adhesively luted three-unit posterior fixed partial dentures (FPD) made of a polyethylene-fibre-reinforced-composite system (PFRC) in comparison with a glass-fibre-reinforced-composite system (GFRC). Therefore the fracture strength and marginal adaptation were examined. A total of 16 FPDs of each material combination were manufactured and adhesively luted to human molars. Before and after an artificial ageing process by thermal cycling and mechanical loading (TCML) the quality of the marginal adaptation was examined by evaluating epoxy replicas in a scanning electron microscope (SEM). After TCML the fracture strength of eight FPDs of each series was tested by mechanical loading them to failure. With the remaining eight FPDs the quality of deeper layers of the luting was examined with a dye penetration technique. The calculated median fracture strength values (25/75% percentiles) were 830 N (643/982) for the PFRC and 884 N (684/1,113) for the GFRC. The SEM analysis showed at least 80% of perfect marginal areas for both material combinations in dentine as well as in enamel before and after TCML. Looking at the cement-tooth interfaces the dye penetration technique showed statistically significant better results for the enamel finishing lines than for those in dentine. With finishing lines in dentine the two material combinations showed statistically significant differences for this interface. Fracture force results as well as marginal quality encourage further clinical investigations on both systems although the GFRC performed slightly better than the PFRC.

Cementation↗
PubMed2001

HSV and glycoprotein J inhibit caspase activation and apoptosis induced by granzyme B or Fas.

HSV-1 inhibits apoptosis of infected cells, presumably to ensure that the infected cell survives long enough to allow completion of viral replication. Because cytotoxic lymphocytes kill their targets via the induction of apoptosis, protection from apoptosis could constitute a mechanism of immune evasion for HSV. Several HSV genes are involved in the inhibition of apoptosis, including Us5, which encodes glycoprotein J (gJ). Viruses deleted for Us5 showed defects in inhibition of caspase activation after Fas ligation or UV irradiation. Transfected cells expressing the Us5 gene product gJ were protected from Fas- or UV-induced apoptosis, as measured by morphology, caspase activation, membrane permeability changes, or mitochondrial transmembrane potential. In contrast, caspase 3 activation in mitochondria-free cell lysates by granzyme (gr)B was inhibited equivalently by Us5 deletion and rescue viruses, suggesting that gJ is not required for HSV to inhibition this process. However, mitochondria-free lysates from transfected cells expressing Us5/gJ were protected from grB-induced caspase activation, suggesting that Us5/gJ is sufficient to inhibit this process. Transfected cells expressing Us5/gJ were also protected from death induced by incubation with purified grB and perforin. These findings suggest that HSV has a comprehensive set of immune evasion functions that antagonize both Fas ligand- and grB-mediated pathways of CTL-induced apoptosis. The understanding of HSV effects on killing by CTL effector mechanisms may shed light on the incomplete control of HSV infections by the immune system and may allow more rational approaches to the development of immune modulatory treatments for HSV infection.

Animals↗
PubMed2001

Substrate specificity determinants of human macrophage elastase (MMP-12) based on the 1.1 A crystal structure.

The macrophage elastase enzyme (MMP-12) expressed mainly in alveolar macrophages has been identified in the mouse lung as the main destructive agent associated with cigarette smoking, which gives rise to emphysema, both directly via elastin degradation and indirectly by disturbing the proteinase/antiproteinase balance via inactivation of the alpha1-proteinase inhibitor (alpha1-PI), the antagonist of the leukocyte elastase. The catalytic domain of human recombinant MMP-12 has been crystallized in complex with the broad-specificity inhibitor batimastat (BB-94). The crystal structure analysis of this complex, determined using X-ray data to 1.1 A and refined to an R-value of 0.165, reveals an overall fold similar to that of other MMPs. However, the S-shaped double loop connecting strands III and IV is fixed closer to the beta-sheet and projects its His172 side-chain further into the rather hydrophobic active-site cleft, defining the S3 and the S1-pockets and separating them from each other to a larger extent than is observed in other MMPs. The S2-site is planar, while the characteristic S1'-subsite is a continuous tube rather than a pocket, in which the MMP-12-specific Thr215 replaces a Val residue otherwise highly conserved in almost all other MMPs. This alteration might allow MMP-12 to accept P1' Arg residues, making it unique among MMPs. The active-site cleft of MMP-12 is well equipped to bind and efficiently cleave the AlaMetPhe-LeuGluAla sequence in the reactive-site loop of alpha1-PI, as occurs experimentally. Similarities in contouring and particularly a common surface hydrophobicity both inside and distant from the active-site cleft explain why MMP-12 shares many substrates with matrilysin (MMP-7). The MMP-12 structure is an excellent template for the structure-based design of specific inhibitors for emphysema therapy and for the construction of mutants to clarify the role of this MMP.

Amino Acid Sequence↗
PubMed2001

Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells.

Chemokines dictate regional trafficking of functionally distinct T cell subsets. In rodents and humans, a unique subset of CD4(+)CD25(+) cytotoxic T lymphocyte antigen (CTLA)-4(+) regulatory T cells (Treg) has been proposed to control peripheral tolerance. However, the molecular basis of immune suppression and the trafficking properties of Treg cells are still unknown. Here, we determined the chemotactic response profile and chemokine receptor expression of human blood-borne CD4(+)CD25(+) Treg cells. These Treg cells were found to vigorously respond to several inflammatory and lymphoid chemokines. Treg cells specifically express the chemokine receptors CCR4 and CCR8 and represent a major subset of circulating CD4(+) T cells responding to the chemokines macrophage-derived chemokine (MDC)/CCL22, thymus and activation-regulated chemokine (TARC)/CCL17, I-309/CCL1, and to the virokine vMIP-I (ligands of CCR4 and CCR8). Blood-borne CD4(+) T cells that migrate in response to CCL1 and CCL22 exhibit a reduced alloproliferative response, dependent on the increased frequency of Treg cells in the migrated population. Importantly, mature dendritic cells preferentially attract Treg cells among circulating CD4(+) T cells, by secretion of CCR4 ligands CCL17 and CCL22. Overall, these results suggest that CCR4 and/or CCR8 may guide Treg cells to sites of antigen presentation in secondary lymphoid tissues and inflamed areas to attenuate T cell activation.

Abatacept↗
PubMed2001

Biphasic response to human galanin of extracellular acidification in human Bowes melanoma cells.

The metabolic response of galanin GAL1 receptor subtype, endogenously expressed in human Bowes melanoma (HBM) cells, was investigated. Cytosensor microphysiometry was used to determine the extracellular acidification rate. A biphasic response, consisting of a rapid increase in the extracellular acidification rate followed by a decrease below the basal level, was observed after perfusion with human galanin. The magnitude and the rate of onset of both phases were dependent on the galanin concentration. The increase in the extracellular acidification rate (maximum of 25% of basal level; -log(EC(50))=7.23+/-0.14) was transient, whereas the following decrease (maximum of 40% of basal level; -log(EC(50))=7.77+/-0.23) was sustained. The EC(50) values for the increase and decrease were in a similar range. After consecutive galanin administration, the magnitude of the response was the same as for the unexposed cells, indicating the absence of galanin receptor desensitization or internalization in HBM cells. Responses were blocked by pretreatment with pertussis toxin and phorbol-12-myristate-13-acetate (PMA), indicating a G-protein/protein kinase C signalling pathway. Our microphysiometry results show a biphasic response of the extracellular acidification rate mediated by the galanin receptor expressed in HBM cells which has not been described previously for any other endogenously expressed neuropeptide receptor.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Screening, confirmation and quantification of diuretics in urine for doping control analysis by high-performance liquid chromatography-atmospheric pressure ionisation tandem mass spectrometry.

A sensitive, selective, robust and fast method to identify 32 diuretics and masking agents in urine is described. The analytical procedure is reduced to a single XAD extraction step for sample preparation, followed by reversed-phase liquid chromatography in combination with atmospheric pressure ionisation/tandem mass spectrometry. This technique is, after minor modifications, suitable for screening analyses and confirmation of identity as well as quantitation of diuretics. Considerations relating to the stability and metabolism of the compounds are given if relevant for routine screening analyses.

Atmospheric Pressure↗
PubMed2001

Cutting edge: Stat6-dependent substrate depletion regulates nitric oxide production.

The cytokines IL-4 and IL-13 inhibit the production of NO from activated macrophages through an unresolved molecular mechanism. We show here that IL-4 and IL-13 regulate NO production through depletion of arginine, the substrate of inducible NO synthase (iNOS). Inhibition of NO production from murine macrophages stimulated with LPS and IFN-gamma by IL-4 or IL-13 was dependent on Stat6, cell density in the cultures, and pretreatment for at least 6 h. IL-4/IL-13 did not interfere with the expression or activity of iNOS but up-regulated arginase I (the liver isoform of arginase) in a Stat6-dependent manner. Addition of exogenous arginine completely restored NO production in IL-4-treated macrophages. Furthermore, impaired killing of the intracellular pathogen Toxoplasma gondii in IL-4-treated macrophages was overcome by supplementing L-arginine. The simple system of regulated substrate competition between arginase and iNOS has implications for understanding the physiological regulation of NO production.

Animals↗
PubMed2001

Transcatheter closure of atrial septal defects and patent foramen ovale under intracardiac echocardiographic guidance: feasibility and comparison with transesophageal echocardiography.

Transesophageal echocardiography (TEE) has been employed successfully for guiding transcatheter device closure of secundum atrial septal defect (ASD) and patent foramen ovale (PFO). However, the use of TEE for device closure requires general anesthesia. Intracardiac echocardiography (ICE) can provide similar anatomical views that might replace the use of TEE for device closure. Eleven patients (eight female/three male) with secundum ASD and PFO associated with strokes underwent attempts at transcatheter closure of their defects under sequential TEE and ICE guidance (six patients) and under ICE alone (five patients). The ages of the patients ranged from 6.6 to 74.7 yr, and their weights ranged from 23 to 124.5 kg. The sizes of the defects, as measured by TEE (six patients), ranged from 3 to 27 mm and, as measured by ICE (11 patients), from 3 to 27 mm. The balloon-stretched diameter of the ASD, as measured by TEE (six patients), ranged from 16 to 38 mm and, as measured by ICE (11 patients), from 16 to 35 mm. Both techniques correlated well for the measured two-dimensional diameter and for the balloon-stretched diameter (r = 0.97 and 0.98, respectively). Both TEE and ICE provided similar views of the defects and the various stages of device deployment. Owing to the proximity of the left atrium to the esophagus, however, the images obtained by ICE were more helpful and informative than those obtained by TEE. All patients experienced successful device placement (six patients under both TEE and ICE; five patients under ICE guidance alone); complete closure of the defects was effected in nine patients, whereas two patients had small residual shunts. There were no complications. We conclude that ICE provides unique images of the atrial communications and measurements similar to those obtained by TEE. ICE potentially could replace TEE as a guiding imaging tool for ASD and PFO device closure, thus eliminating the need for general anesthesia.

Adolescent↗
PubMed2001

Multiple roles of neurotrypsin in tissue morphogenesis and nervous system development suggested by the mRNA expression pattern.

We have mapped the spatio-temporal expression of the multidomain serine protease neurotrypsin in the developing mouse by in situ hybridization. On embryonic day (E) 8, mRNA is detected in giant trophoblast cells, later in embryonic mesenchymal tissues. On E11, expression begins in Schwann cell precursors, olfactory epithelium, trigeminal ganglion, and midbrain. The floor plate shows strong expression on E12. Further prenatal development is characterized by rising neurotrypsin mRNA in sensory ganglia and motor neurons. Staining in cerebral cortex emerges around birth and culminates toward the end of the first week with a complex laminar and areal pattern. Expression in peripheral nerves and nonneural tissues vanishes soon after birth and the adult neuronal distribution is gradually established until weaning age. This developmental expression pattern suggests roles of neurotrypsin in morphogenesis of nonneural tissues, as well as in neural development, in particular in axonal target invasion, synaptogenesis, and Schwann cell differentiation.

Aging↗
PubMed2001

Glass fiber-reinforced abutments for dental implants. A pilot study.

Titanium abutments in dental implants shine through all-ceramic crowns and therefore limit excellent esthetic results. Prototypes of tooth-colored fiber-reinforced abutments were investigated to avoid the shining-through effect. In vitro, the fracture strength was determined after thermal cycling and mechanical loading of all-ceramic single crowns and four-unit bridges made of a fiber-reinforced composite. The suprastructures were adhesively fixed onto fiber-reinforced implant abutments and compared with those fixed on standard titanium abutments. The median of the fracture strength of the titanium-supported all-ceramic crowns was significantly higher than the median of crowns fixed onto the prototypes. But this value was still more than twice as high as the maximum loading force under oral conditions. No statistical difference was found between four-unit bridges made by fiber-reinforced composite inserted onto titanium abutments and those inserted onto fiber-reinforced abutments. Fiber-reinforced abutment prototypes for dental implants avoided the shining-through effect associated with metal abutments. Their load-bearing capacity after in vitro stress simulation was higher than the maximum oral loading force. With some improvements, the fiber-reinforced implant abutments are therefore a promising alternative to titanium abutments.

Composite Resins↗
PubMed2001

Glass-fibre-reinforced-composite fixed partial dentures on dental implants.

UNLABELLED: The objective was to investigate the fracture strength and marginal fit of implant suprastructures made of fibre-reinforced composite which were fixed onto the implants using cementation or screws. A sample (n=8) of 4-unit bridges, made of the fibre-reinforced composite Vectris/Targis, were adhesively cemented onto titanium conical implant abutments. The second sample consisted of eight screwable Vectris/Targis bridges which were based on prototypes of titanium crown bases. After a 5 year simulation of thermal cycling and mechanical loading (TCML), all specimen were loaded to fracture. Marginal fit was investigated using a semiquantitative SEM analysis. The cemented 4-unit bridges showed a fracture strength of 1553 N (Q1=1498 N, Q3=1825 N) and the screw-fixed bridges had a median of 1457 N (Q1=1223 N, Q3= 1781 N). The analysis of the marginal adaptation showed similar results of cemented and screwed bridges. The bond between the Targis facing-material and the composite cement was significantly deteriorated after TCML. CONCLUSION: Suprastructures made of glass-fibre-reinforced composite could become an alternative to reconstructions with a metal-framework. Both, fixation onto the implants with screws or cementation, are possible.

Composite Resins↗
PubMed2001

Enhanced detection criteria in implantable cardioverter defibrillators: sensitivity and specificity of the stability algorithm at different heart rates.

The lack of specificity in the detection of ventricular tachyarrhythmias remains a major clinical problem in the therapy with ICDs. The stability criterion has been shown to be useful in discriminating ventricular tachyarrhythmias characterized by a small variation in cycle lengths from AF with rapid ventricular response presenting a higher degree of variability of RR intervals. But RR variability decreases with increasing heart rate during AF. Therefore, the aim of the study was to determine if the sensitivity and specificity of the STABILITY algorithm for spontaneous tachyarrhythmias is related to ventricular rate. Forty-two patients who had received an ICD (CPI Ventak Mini I, II, III or Ventak AV) were enrolled in the study. Two hundred ninety-eight episodes of AF with rapid ventricular response and 817 episodes of ventricular tachyarrhythmias were analyzed. Sensitivity and specificity in the detection of ventricular tachyarrhythmias were calculated at different heart rates. When a stability value of 30 ms was programmed the result was a sensitivity of 82.7% and a specificity of 91.4% in the detection of slow ventricular tachyarrhythmias (heart rate < 150 beats/min). When faster ventricular tachyarrhythmias with rates between 150 and 169 beats/min (170-189 beats/min) were analyzed, a stability value of 30 ms provided a sensitivity of 94.5% (94.7%) and a specificity of 76.5% (54.0%). For arrhythmia episodes > or = 190 beats/min, the same stability value resulted in a sensitivity of 78.2% and a specificity of 41.0%. Even when other stability values were taken into consideration, no acceptable sensitivity/specificity values could be obtained in this subgroup. RR variability decreases with increasing heart rate during AF while RR variability remains almost constant at different cycle lengths during ventricular tachyarrhythmias. Thus, acceptable performance of the STABILITY algorithm appears to be limited to ventricular rate zones < 170 beats/min.

Aged↗
PubMed2001

Excretion of sweat and urine pyridinoline crosslinks in healthy controls and subjects with established metabolic bone disease.

Convenient techniques for measuring rates of bone turnover have been developed in recent years with the advent of biochemical markers of bone metabolism. One recent of these techniques is a collection method and quantitative enzyme immunoassay for free pyridinoline crosslinks in human sweat. The concentrations of pyridinoline crosslinks in 5-day sweat collections and first morning void and 24-hour urine collections from healthy subjects and subjects with established metabolic bone disorders were determined. T-scores were higher in the sweat system than in the urine system by up to 10-fold in postmenopausal subjects, women with hyperparathyroidism, and subjects with postmenopausal osteoporosis. For subjects with postmenopausal osteoporosis, receiver-operating characteristic curve analysis yielded areas under the curve of 0.699, 0.629, and 0.520 for sweat pyridinoline, first morning void urine pyridinoline, and 24 hour urine pyridinoline respectively. The areas under the curve of the sweat and first morning void urine measurements were significantly greater (p<0.05) than the 24-hour pyridinoline measurements. Healthy postmenopausal subjects and subjects with postmenopausal osteoporosis were monitored before and during estrogen replacement therapy or alendronate therapy. Sweat pyridinoline values declined by 49.0 +/- 12.4% and 19.4 +/- 19.9% for estrogen and alendronate subjects respectively. We conclude that this non-invasive technique is a sensitive and specific measure of bone resorption and is appropriate as an adjunct to techniques such as bone density and may also be useful in monitoring of response to anti-resorptive therapies.

Adult↗
PubMed2001

Severe complications of varicella in previously healthy children in Germany: a 1-year survey.

OBJECTIVE: Varicella is a common infectious disease, usually benign and self-limited, and complications are believed to be rare. The purpose of this study was to describe the epidemiology of severe varicella complications in immunologically healthy children in Germany. METHODS: Information on any admission of children with a severe complication associated with chickenpox was solicited throughout 1997 from all 485 pediatric hospitals in Germany using an established surveillance system. The case definition included nonimmunocompromised individuals who were up to 16 years of age and hospitalized with neurologic complications, bacterial superinfections, or hematologic complications. RESULTS: The response rate to the surveillance questionnaire during the observation period was high: 93.4%. Of the 153 reported cases, 119 met the case definition. There was a seasonal distribution of reported complications with a peak in March. The majority of complications occurred in preschool-age children with a maximum age of 4 years. No gender predominance was found with a distribution of 56 female and 63 male patients. Multiple entries for complications were allowed. The most frequent complications were neurologic, which were reported in 73 children (61.3%); cerebellitis was the leading diagnosis (n = 48), followed by encephalitis (n = 22), meningitis (n = 2), and central facial palsy (n = 1). A total of 46 (38.6%) infectious complications were identified. Superinfections of the skin were present in 31 (26.0%), pyogenic arthritis was present in 5 (4.2%), osteomyelitis was present in 4 (3.3%), necrotizing fasciitis was present in 3 (2.5%), orbital cellulitis was present in 2 (1.6%), and pneumonia was present in 1 (0.8%). Streptococcus pyogenes was the leading cause of bacterial infections (18 cases [15.1%]), with invasive disease in 6 patients (8.4%) and linked to 4 of 8 cases with defect healing. Infectious complications were reported in the majority in younger children up to 4 years of age, whereas neurologic complications occurred more frequently in an older age range. Five children experienced thrombocytopenia or severe anemia. There was no bleeding disorder, no fatality, and no case of Reye syndrome reported during the 1-year observation period. In total, 8 (6.7%) of 119 patients reported having long-term sequelae, 6 attributable to infectious complications and 2 to persistent deficits after neurologic complications. CONCLUSION: This is the first prospective nationwide study of severe complications of varicella in immunologically healthy children. Related to 14 025 867 children up to the age of 16, a crude incidence of severe chickenpox complications of 0.85/100 000 could be calculated [corrected]. The actual hospitalization rate attributable to complicated chickenpox is probably much higher, because this calculation refers to a population theoretically at risk and not the truly susceptible individuals. The results of this study demonstrate considerable morbidity with a comparatively high rate of encephalitis, osteomyelitis, and pyogenic arthritis. Although infectious complications were present in only 38.6% of the reported cases, they contributed disproportionately to the cases with chronic sequelae. Looking at these cases in more detail, S pyogenes involvement was identified as the major risk factor for invasive disease with an unfavorable long-term outcome. varicella-zoster virus, chickenpox/epidemiology, chickenpox/complications, encephalitis, cellulitis, osteomyelitis, necrotizing fasciitis, group A beta-hemolytic streptococci, Europe.

Adolescent↗
PubMed2001

[Cytomeglovirus infection after liver transplantation].

OBJECTIVE: To study the prophylaxis, diagnosis and treatment of cytomegalovirus (CMV) infection after liver transplantation. METHODS: The clinical data of 10 patients receiving liver transplantation from July 1999 to October 2000 in our hospital were retrospectively analyzed along with literature review. RESULTS: CMV infection occurred asymptomatic cally in 6 patients, of whom, 5 were cured. CONCLUSIONS: Fluorogenic quantitative PCR (FQ-PCR) is effective, sensitive and highly specific for detecting CMV infection. It is important to monitor the status of CMV infection in patients receiving liver transplantation preoperatively and postoperatively. The key point for prophylaxis and treatment of CMV infection is early prevention and treatment after operation. Ganciclovir can exert significant therapeutic effects on CMV infection.

Adult↗
PubMed2000

Interferon-beta treatment in multiple sclerosis patients decreases the number of circulating T cells producing interferon-gamma and interleukin-4.

Systemic administration of interferon (IFN)-beta has been recently approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The immunological mechanism by which IFN-beta ameliorates MS is still partially unknown. We measured the number of blood circulating CD4(+), CD4(-), CD8(+), and CD8(-) T cells secreting IFN-gamma and IL-4 in 26 RRMS patients followed for up to 9 months of an alternate day s.c. treatment with 8x16 IU of IFN-beta1b. Compared to pre-treatment values, a significant (P<0.05) reduction of CD4(+), CD4(-), CD8(+) and CD8(-) cells producing IFN-gamma and of CD4(+) and CD4(-) cells producing IL-4 was observed in MS patients. The IFN-beta-associated effect was evident soon after the beginning of the treatment and persisted for the entire follow-up period. We did not observe any effect of IFN-beta treatment on the percentage of IL-4-producing CD8(+) and CD8(-) cells nor in that of natural killer (NK) cells producing IFN-gamma. Our results show that IFN-beta treatment in MS patients induces a profound and persistent down-regulation of the number of circulating T cells secreting IFN-gamma and IL-4 thus suggesting a broader rather than a specific immunomodulatory effect of IFN-beta in MS.

Adjuvants, Immunologic↗