IgE-mediated allergy to castor bean dust in a landscape gardener.
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Adult↗
Biomedical subjects
G Metz
Publications and source records attributed to G Metz.
Long-term results of hysteroscopic myomectomy for abnormal uterine bleeding.
OBJECTIVE: To analyze the efficacy of transcervical resection of submucous myomas and to identify prognostic factors for long-term results. METHODS: Two-hundred eighty-five women were treated with transcervical resection of submucous myomas without endometrial ablation. In case of incomplete resection a repeat procedure was offered. Long-term follow-up was obtained. Recurrence was defined as the need for further surgery. The relation of several variables with the outcome was analyzed using Cox proportional hazard regression analysis. RESULTS: Seventeen cases (6%) were lost to follow-up. The median follow-up was 46 months (range 1-104 months); for cases without recurrence median follow-up was 42 months (range 16-104 months). Forty-one (14.5%) patients had repeat surgery. An independent prognostic value of uterine size (P < .001) and number of submucous myomas (P < .001) for recurrence was noted. Twenty of 41 patients who had repeat surgery subsequently had a hysterectomy. None of the variables investigated predicted the need for hysterectomy. The surgery-free percentage of 165 patients with normal sized uteri and not more than two myomas was 94.3% (standard error +/- 1.8%) at 2 years and 90.3% (+/- 3.0%) at 5 years. CONCLUSION: Transcervical resection of submucous myomas is a safe and effective treatment for patients with a normal sized uterus and not more than two myomas. It is an acceptable alternative for selected other patients. The need for a combined endometrial ablation is questionable. Transcervical resection of submucous myomas will give patients a high chance of averting further surgery and should modify the way patients are counseled.
Adult↗
Decreased release of histamine and sulfidoleukotrienes by human peripheral blood leukocytes after wasp venom immunotherapy is partially due to induction of IL-10 and IFN-gamma production of T cells.
BACKGROUND: Recent studies provide evidence that venom immunotherapy (VIT) alters the pattern of cytokine production by inducing an allergen-specific T-cell shift in cytokine expression from TH2 (IL-4, IL-5) to TH1 (IFN-gamma) cytokines and also inducing the production of IL-10. OBJECTIVE: This study was carried out to analyze whether these changes in cytokine production of T cells already observed 1 week after the initiation of VIT in subjects with wasp venom allergy also influence the reactivity of effector cells, such as mast cells and basophils. METHODS: All subjects included in this study had a history of severe systemic allergic reactions to wasp stings and positive skin test responses with venom and venom-specific IgE in the sera. Peripheral blood leukocytes were isolated before and after the initiation of VIT (rush therapy reaching a maintenance dose of 100 microg venom injected subcutaneously within 1 week) and preincubated with or without addition of IL-10, IFN-gamma, IL-10 + IFN-gamma, anti-IL-10, or anti-IFN-gamma. After stimulation with wasp venom, histamine and sulfidoleukotriene release were assessed by ELISA and compared with spontaneous release and total histamine content. RESULTS: After the induction of VIT, venom-induced absolute and relative histamine and sulfidoleukotriene release were reduced. This was at least partially due to the induction of IFN-gamma and IL-10 production, because (1) neutralization of IL-10 and IFN-gamma by mAbs partially restored the release after the initiation of VIT and (2) the addition of exogenous IFN-gamma and IL-10 caused a statistically significant diminution of the venom-induced histamine and sulfidoleukotriene release before VIT. Depletion of CD2(+) T cells also restored the releasability after VIT. CONCLUSION: These data indicate that T cells (producing IL-10 and IFN-gamma after VIT) play a key role for the inhibition of histamine and sulfidoleukotriene release of effector cells.
Antibodies, Monoclonal↗
Insect venom immunotherapy induces interleukin-10 production and a Th2-to-Th1 shift, and changes surface marker expression in venom-allergic subjects.
The current study was carried out to elucidate the immunoregulatory changes induced by venom immunotherapy (VIT) in bee or wasp allergic subjects. All subjects included in this study had a history of severe systemic allergic reactions to stings of the respective insect as well as positive skin tests with the respective venom or venom-specific IgE in the sera. Parameters assessed in peripheral blood mononuclear cells (PBMC) before and after initiation of VIT (rush therapy reaching a maintenance dose of 100 micrograms venom injected subcutaneously within 1 week) were expression of CD3, CD4, CD8, CD45RA, CD45RO, interleukin (IL)-2 receptor (R) alpha, IL-4R, IL-12R, Fc epsilon RII, CD40, and CD40 ligand (CD40L), cells producing interferon (IFN)-gamma and IL-10 after stimulation with phorbol 12-myristate 13-acetate + ionomycin in the presence of monensin measured by flow cytometry; secretion of IFN-gamma, IL-4, and IL-10 measured by ELISA (IFN-gamma and IL-10 were additionally measured by PCR), and proliferation after stimulation with the respective venom. Significant decreases were observed after VIT for proliferative response to venom and venom + IL-4, IL-4 secretion, Fc epsilon RII, CD40, and CD40L expression. Significant increases were observed after VIT for IFN-gamma concerning the amount secreted and the number of producing cells, and IL-10, IL-10 was mainly produced by CD4+ cells that were negative for IFN-gamma, but some double-positive (IL-10 and IFN-gamma) cells were always detected. Addition of blocking anti-IL-10 antibodies, but not isotype control antibodies, prevented down-regulation of proliferation (but not IL-4 secretion) and further enhanced IFN-gamma secretion after VIT. These data indicate that in insect venom allergic subjects, VIT not only induces a rapid shift in cytokine expression from Th2 to Th1 cytokines, but also leads to induction of the immunosuppressive cytokine IL-10, which may be important for the limitation of potentially harmful allergen-specific Th1 responses. The described changes in cytokine expression may be responsible for subsequent increases in allergen-specific IgG and decreases in IgE production, as well as suppressive activity observed in earlier studies.
Allergens↗
Solid-state 13C-NMR of [(3-13C)Pro]bacteriorhodopsin and [(4-13C)Pro]bacteriorhodopsin: evidence for a flexible segment of the C-terminal tail.
The configuration of an Xaa-Pro bond can be determined by solid-state magic-angle-sample-spinning (MASS)-13C-NMR spectroscopy since the chemical shifts of C beta and Cgamma of the proline ring are sensitive to the isomerization state of the preceding peptide bond. (3-13C)Pro and (4-13C)Pro have been chemically synthesized; the former by means of an asymmetric synthesis. The 13C-labeled Pro residues were biosynthetically incorporated into bacteriorhodopsin with a yield of 80%. The solid-state-MASS-13C-NMR spectra of [(3-13C)Pro]bacteriorhodopsin and [(4-13C)Pro]bacteriorhodopsin revealed isotropic chemical shifts at 29.8 ppm and 25.5 ppm, respectively. From the chemical-shift values we conclude that all Xaa Pro peptide bonds are in the trans configuration confirming previous results from solution-NMR studies on solubilized bacteriorhodopsin in organic solvents [Deber, M.C., Sorrell, B.J. & Xu, G.Y. (1990) Biochem. Biophys. Res. Commun. 172, 862-869]. Inversion-recovery experiments could differentiate between three classes of Pro residues distinguished by their relaxation time t1. Tentatively, these three distinct groups of Pro residues could be assigned to the helical, the loop, and the C-terminal parts of the protein. The resonances of the two C-terminal Pro could be identified by removing the C-terminus by proteolysis. Although they are separated by only one Glu they occupy different chemical environments and possess different flexibilities. These results indicate that the first part of the C-terminal tail is constrained. Pro238 marks the position where the tail becomes freely mobile. It is proposed that the C-terminus is fixed to the membrane via salt bridges between divalent cations and negative charges of the C-terminus as well as interhelical loops.
Bacteriorhodopsins↗
Towards quantitative CP-MAS NMR.
Many of the combined cross polarization-magic angle spinning (CP-MAS) experiments that have been developed over the past ten years for structural studies of chemical and biological systems rely on the measurement of quantitative signal intensities. However, one of the drawbacks of the CP technique is that the efficiency of polarization transfer depends on the strength of the heteronuclear dipolar interaction which is generally different for different chemical groups. In this paper, we propose the use of a linear ramp of CP amplitudes in combination with high speed MAS to improve signal quantitation. The linear ramp is centered on one of the sidebands of the Hartmann-Hahn matching profile and the contact time is chosen to maximize the total signal in the CP-MAS spectrum. The approach is illustrated on N-t-Boc-alanine whose six carbons exhibit a range of heteronuclear dipolar couplings and molecular motions.
Alanine↗
Nitric oxide production is increased in patients after burn injury.
OBJECTIVE: Human burn injury is associated with an inflammatory response and related hyperdynamic cardiovascular profile. Increased production of nitric oxide (NO), a potent endogenous vasodilator, has been reported in patients with inflammatory states, including sepsis, but not after trauma other than burns. We studied whether plasma levels of the stable byproducts of NO, nitrite (NO2-) and nitrate (NO3-), are increased in burn patients. DESIGN: Prospective controlled study. PATIENTS AND METHODS: In consecutive patients admitted to the intensive care unit of the burn center at the Queen Astrid Military Hospital in Brussels, plasma was drawn daily from day 1 to day 5 postadmission for determination of NO2-/NO3- levels (Griess' reaction). In a control group of nonseptic inpatients from the department of neurology in Erasme University Hospital who were matched for nutrition (30 to 40 kcal/kg/day of a standard enteral solution), plasma was drawn once for NO2-/NO3- determination. MEASUREMENTS AND MAIN RESULTS: The burn group included 16 patients (age 35 +/- 18 years, total burn surface area (TBSA) 37 +/- 19%) and the control group included six patients (age 64 +/- 18 years). For each comparison between the groups, NO2-/NO3- plasma levels were higher in those patients with burns than in the control group. In the burn group, there was no correlation between NO2-/NO3- plasma levels and TBSA, age, TBSA x age, blood pressure or time. However, in a subgroup of five burned patients who became septic during the study period, NO2-/NO3- plasma levels were slightly higher than in the non-infected patients (177 +/- 131 vs. 83 +/- 48 micromoles/L, NS). CONCLUSION: Human burn injury is associated with an increase in NO production. In this small-size study, NO production was not proportional to burn area, and seemed to be further enhanced in septic patients.
Adolescent↗
Effects of methylene blue on oxygen availability and regional blood flow during endotoxic shock.
OBJECTIVE: We hypothesized that methylene blue, by inhibiting the activation of soluble guanylate cyclase mediated by nitric oxide, may reverse systemic hypotension, enhance myocardial function, and improve peripheral distribution of blood flow during endotoxic shock. DESIGN: Randomized, controlled, acute intervention study. SETTING: University intensive care laboratory. SUBJECTS: Twenty-one healthy, anesthetized, mongrel dogs, weighing 26 +/- 4 kg. INTERVENTIONS: Groups 1 (n = 7) and 2 (n = 7) received endotoxin (2 mg/kg iv) alone combined with increasing doses of 2.5, 5, 10, and 20 mg/kg iv of methylene blue. Each dose was administrated for 30 mins with a free interval of 30 mins. Group 3 (n = 7) served as a control group, receiving the same doses of methylene blue in the absence of endotoxin. All animals were given normal saline to keep cardiac filling pressures constant. Blood flow probes were placed around the superior mesenteric, renal, and femoral arteries to measure regional blood flow by ultrasonic technique. Data were collected every 30 mins during the study. MEASUREMENTS AND MAIN RESULTS: After endotoxemia, methylene blue increased systemic and pulmonary arterial pressure and vascular resistances in a dose-dependent manner up to 10 mg/kg, but had no effect on cardiac index. At the highest dose, methylene blue decreased arterial pressure and systemic vascular resistance. At doses of methylene blue of < or = 10 mg/kg, mesenteric and femoral blood artery flow increased. At the highest dose of 20 mg/kg, femoral artery blood flow further increased, but mesenteric blood flow decreased. Renal artery blood flow was unaffected by methylene blue. In the absence of endotoxin, methylene blue at doses of 2.5 or 5 mg/kg did not alter mean arterial pressure, but reduced cardiac index, indicating an increase in systemic vascular resistance. In contrast, the higher doses of 10 or 20 mg/kg of methylene blue decreased mean arterial pressure and systemic vascular resistance. However, pulmonary arterial pressure and pulmonary vascular resistance increased in a dose-dependent manner. Mesenteric and renal artery blood flow decreased but femoral blood flow increased. As in the presence of endotoxin, methylene blue induced dose-related increases in oxygen uptake and oxygen extraction ratio, but did not alter oxygen delivery. Methylene blue largely attenuated the endotoxin-induced increase in plasma nitrite concentrations. CONCLUSIONS: Low and moderate doses of methylene blue can significantly increase arterial blood pressure but not cardiac index during endotoxic shock. Methylene blue infusion may selectively increase mesenteric blood flow. High doses of methylene blue can worsen systemic hypotension, myocardial depression, and pulmonary hypertension after endotoxemia.
Animals↗
Tirilazad mesylate (U-74006F) inhibits effects of endotoxin in dogs.
The present study explored the effects of a potent antioxidant, the 21-aminosteroid U-74006F, on the systemic and regional hemodynamics and the oxygen extraction capabilities during endotoxic shock. Twenty-four anesthetized dogs were randomized into three groups. Group 1 (n = 8) served as control. Group 2 (n = 8) and group 3 (n = 8) received 2 mg/kg iv of Escherichia coli endotoxin, followed 30 min later by saline infusion. Group 3 was given U-74006F as an intravenous bolus of 80 micrograms/kg followed by an infusion of 10 micrograms.kg-1.min-1, and group 2 received an equivalent volume of vehicle. Tamponade was induced 30 min later to study the oxygen extraction capabilities of the animals. Compared with the endotoxin-alone group, the U-74006F-treated dogs maintained higher mean arterial pressure, cardiac index, stroke volume index, and left ventricular stroke work index and lower pulmonary vascular resistance. They also showed a higher fractional blood flow to mesenteric and renal beds. Endotoxin administration increased whole body critical oxygen delivery (DO2crit) from 7.7 +/- 2.4 to 12.0 +/- 1.9 ml.kg-1.min-1 (P < 0.05), but U-74006F decreased DO2crit to 7.8 +/- 2.0 ml.kg-1.min-1 (P < 0.05 vs. endotoxin alone). Endotoxin decreased critical oxygen extraction ratio (O2ERcrit) from 75.0 +/- 12.7 to 44.3 +/- 8.7% (P < 0.05), but U-74006F increased O2ERcrit to 64.1 +/- 11.2% (P < 0.05 vs. endotoxin alone). U-74006F also decreased endotoxin-induced elevation of mesenteric and renal DO2crit and markedly increased regional O2ERcrit. Systemic and regional blood lactate concentrations were lower in the U-74006F-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Interferon-gamma-activated immature macrophages exhibit a high Trypanosoma cruzi infection rate associated with a low production of both nitric oxide and tumor necrosis factor-alpha.
Murine peritoneal macrophages (MPM) can be subdivided into two subpopulations of mature and immature macrophages. In contrast to mature macrophages, immature ones were highly susceptible to Trypanosoma cruzi infection. This highly susceptibility was associated with a low production of alpha 2-macroglobulin. Interferon-gamma (IFN-gamma)-activated immature macrophages also exhibited a higher infection rate than did IFN-gamma-activated mature ones. This higher rate of infection was associated with a low production of both nitric oxide (N = O) and tumor necrosis factor-alpha (TNF-alpha). In contrast, mature MPM showed a lower rate of infection and produced higher levels of N = O and TFN-alpha. Taken together, these results show a clear-cut difference in the course of T. cruzi infection in relation to the macrophage maturation state.
Animals↗
Trypanosoma cruzi upregulates nitric oxide release by IFN-gamma-preactivated macrophages, limiting cell infection independently of the respiratory burst.
The relationship between nitric oxide (N = O) produced by mouse peritoneal macrophages (MPM) and Trypanosoma cruzi infection is still poorly understood. The conditions of MPM activation by gamma-interferon (IFN-gamma) to trigger a N = O-dependent trypanocidal activity, as well as the effect of parasite infection or of reactive oxygen species (ROS) inhibitors on the N = O release were studied. T. cruzi infection occurring after a previous 24 h MPM activation induced an enhancement of nitrite levels (the stable degradation product of N = O) in cell supernatants; both the percentage of infected MPM and the number of amastigotes per infected cell were decreased in comparison to infected but non-activated MPM. Addition of superoxide dismutase or catalase to non-infected but activated MPM increased the nitrite levels; these were not detectable when L-arginine inhibitors were added together with ROS inhibitors. The latter had no effect on infection nor on nitrite levels when infection occurred after pre-activation, and induced only a weak nitrite release when infection took place before MPM activation. Altogether, these results support the involvement of N = O in the inhibition of T. cruzi infection by IFN-gamma-preactivated macrophages, together with the upregulation of N = O release by T. cruzi infection independently of the respiratory burst.
Animals↗
Asp85 is the only internal aspartic acid that gets protonated in the M intermediate and the purple-to-blue transition of bacteriorhodopsin. A solid-state 13C CP-MAS NMR investigation.
High-resolution solid-state 13C NMR spectra of the ground state and M intermediate of the bacteriorhodopsin mutant D96N with the isotope label at [4-13C]Asp and [11-13C]Trp were recorded. The NMR spectra show that Asp85 is protonated in the M intermediate. The environment of Asp85 is quite hydrophobic. On the other hand, Asp212 remains deprotonated and a slight shift to lower field indicates a more hydrophilic environment. Asp85 also protonates in the purple-to-blue transition of bacteriorhodopsin in the deionized membrane, where it experiences a similar environment to M. The shift of Trp resonances in M reflect a conformational change of the protein in forming the M intermediate.
Aspartic Acid↗
High-resolution solid state 13C NMR of bacteriorhodopsin: characterization of [4-13C]Asp resonances.
Solid state 13C nuclear magnetic resonance measurements of bacteriorhodopsin labeled with [4-13C]Asp show that resonances of single amino acids can be resolved. In order to assign and characterize the resonances of specific Asp residues, three different approaches were used. (1) Determination of the chemical shift anisotropy from side-band intensities provides information about the protonation state of Asp residues. (2) Relaxation studies and T1 filtering allow one to discriminate between resonances with different mobility. (3) A comparison of the spectra of light- and dark-adapted bacteriorhodopsin provides evidence for resonances from aspartic acid residues in close neighborhood of the chromophore. In agreement with other investigations, four resonances are assigned to internal residues. Two of them are protonated in the ground state up to pH 10 (Asp96 and Asp115). All other detected resonances, including Asp85 and Asp212, are due to deprotonated aspartic acid. Two lines due to the two internal deprotonated groups change upon dark and light adaptation, whereas the protonated Asp residues are unaffected.
Amino Acid Sequence↗
Wilson's disease in adults with cirrhosis but no neurological abnormalities.
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Adult↗
High resolution 13C-solid state NMR of bacteriorhodopsin: assignment of specific aspartic acids and structural implications of single site mutations.
Three mutant strains of Halobacterium sp. GRB with the site of mutation in the bacterioopsin gene (PM 326: Asp96----Asn; PM 374: Asp96----Gly; PM 384: Asp85----Glu) were grown in a synthetic medium containing (4-13C)-Asp. The mutant bacteriorhodopsins labeled with (4-13C)-Asp (37%-45%), and owing to the metabolism of Halobacteria also with (11-13C)-Trp (50%-100%), were isolated as purple membranes and 13C Solid State Magic Angle Sample Spinning (MASS) Nuclear Magnetic Resonance (NMR) spectra of the samples were taken. The Asp96 mutants lacked the signal at 171.3 ppm which was previously assigned to a protonated internal Asp (Engelhard et al. 1989a). This observation supports the conclusion that Asp96 is protonated in the ground state. PM 384 (Asp85----Glu) has an absorption maximum at 610 nm. It can be converted into a purple form (lambda max = 540 nm) by treatment with a detergent (CHAPSO). The NMR-spectra of these two species differ from each other and from the wild type. The intensity of the resonance at 173 ppm in the wild type spectrum is reduced in both forms of the mutant protein. It is probable that this signal is caused by Asp85. The amino acid changes result not only in a perturbation of their direct environment but also effects on Trp residues and the chromophore protein interaction can be observed.
Aspartic Acid↗
[Emergency intubation and ventilation therapy in severe bronchial asthma].
37 patients were treated with emergency intubation because of severe asthma bronchiale. In 30 patients the usual bronchospasmolytic therapy was ineffective, 12 patients were under permanent treatment. Halothane produced immediate and unequivocal improvement of respiratory global insufficiency and resolution of bronchospasm in 8 out of 13 patients, ketamine in 6 of 18 and a combination of both drugs in 4 of 9 patients. Both drugs are an efficient complement to conventional emergency treatment. A step-by-step schema for anaesthesia in severe asthma bronchiale requiring intubation is presented.
Aged↗
Magic angle sample spinning 13C nuclear magnetic resonance of isotopically labeled bacteriorhodopsin.
Bacteriorhodopsin (bR), the light-driven proton pump protein from Halobacterium halobium, was biosynthetically labeled with [4-13C]Asp. The incorporation yield was 48%. The magic angle sample spinning (MASS) 13C nuclear magnetic resonance (NMR) spectrum of this sample revealed six different peaks superimposed on a broad band of naturally abundant peptide-bond 13C. Two of the six carbonyl signals can be attributed to internal-protonated Asp carboxyl groups, one of which might be Asp115. An additional resonance at 110 ppm can be associated with the C-11 carbon of Trp, indicating an unusual biosynthetic pathway of this amino acid in Halobacterium halobium. Similar measurements performed on papain-treated purple membrane which lacks the C-terminal tail display two new intense signals at 178 and 178.9 ppm. If the same spectrum is taken without cross-polarization, these signals do not decrease or disappear. On the basis of their intensities and their chemical shifts, one can assign in addition to the C-terminal Asp four Asp residues facing the cytoplasmic phase. In native bR, at least two of these form a salt-bridge-like bond which also might include the C-terminal tail. These experiments not only provide data about the chemical environment of the Asp residues within the hydrophobic core of bacteriorhodopsin but also yield information about the interactions between surface components.
Amino Acid Sequence↗