Novel perspectives on hepatitis B vaccine in dialysis population.
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Biomedical subjects
Publications and source records attributed to P Martin.
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We describe a patient suffering from infection of the upper respiratory tract, who was treated with a dose of 4 x 4 g of piperacillin over 10 days. Two days after the end of the treatment, she developed jaundice and had elevated alkaline phosphatase, gammaglutamyltransferase and transaminases. After exclusion of viral hepatitis, a vascular problem, and gall stone disease, the possibility of piperacillin-induced hepatitis was discussed. Lymphocyte transformation test for piperacillin was positive, suggesting an immunological mechanism for the observed hepatopathy. The patient was discharged a few days after in good clinical condition and with reduced liver values. Cholestasis gradually decreased but was detectable for several weeks. The patient had a full clinical and biochemical recovery after 2 months. We conclude that short-term therapy with piperacillin can lead to the same type of hepatopathy as described for amoxycillin/clavulanic acid or antistaphylococcal penicillins. Positive lymphocyte transformation is compatible with an immunological mechanism.
A 5-kb long transcript encoding the stearoyl-CoA desaturase (SCD) was identified by Northern-blot analysis of poly(A)+ mRNA from caprine lactating mammary gland. Complete sequencing of the SCD cDNA (5123 bp) revealed that the coding region (1080 nt) is followed by an unusually long (3.8 kb) 3'-UTR sequence, deriving from a single exon, in which a polymorphism, due to the deletion of a nucleotide triplet, was detected. The complete structural organization of the relevant gene has been determined. The transcription unit was shown to span a 15-kb region and to consist in six exons varying in size from 131 (3rd exon) to 4047 bp (6th exon), and five introns varying in size from 600 to 3700 bp. Using the fluorescence in situ hybridization technique, the SCD gene was localized to bovine and caprine chromosomes 26q21, and ovine chromosome 22q21.
The duration of immunodeficiency following marrow transplantation is not known. Questionnaires were used to study the infection rates in 72 patients surviving 20 to 30 years after marrow grafting. Furthermore, in 33 of the 72 patients and in 16 donors (siblings who originally donated the marrow) leukocyte subsets were assessed by flow cytometry. T-cell receptor excision circles (TRECs), markers of T cells generated de novo, were quantitated by real-time polymerase chain reaction. Immunoglobulin G(2) (IgG(2)) and antigen-specific IgG levels were determined by enzyme-linked immunosorbent assay. Infections diagnosed more than [corrected] 15 years after transplantation occurred rarely. The average rate was 0.07 infections per patient-year (one infection every 14 years), excluding respiratory tract infections, gastroenteritis, lip sores, and hepatitis C. The counts of circulating monocytes, natural killer cells, B cells, CD4 T cells, and CD8 T cells in the patients were not lower than in the donors. The counts of TREC(+) CD4 T cells in transplant recipients younger than age 18 years (at the time of transplantation) were not different from the counts in their donors. In contrast, the counts of TREC(+) CD4 T cells were lower in transplant recipients age 18 years or older, even in those with no history of clinical extensive chronic graft-versus-host disease, compared with their donors. The levels of total IgG(2) and specific IgG against Haemophilus influenzae and Streptococcus pneumoniae were similar in patients and donors. Overall, the immunity of patients surviving 20 to 30 years after transplantation is normal or near normal. Patients who received transplants in adulthood have a clinically insignificant deficiency of de novo-generated CD4 T cells, suggesting that in these patients the posttransplantation thymic insufficiency may not be fully reversible.
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The auditory system's ability to interpret sounds over a wide range of amplitudes rests on the nonlinear responsiveness of the ear. Whether measured by basilar-membrane vibration, nerve-fiber activity, or perceived loudness, the ear is most sensitive to small signals and grows progressively less responsive as stimulation becomes stronger. Seeking a correlate of this behavior at the level of mechanoelectrical transduction, we examined the responses of hair bundles to direct mechanical stimulation. As reported by the motion of an attached glass fiber, an active hair bundle from the bullfrog's sacculus oscillates spontaneously. Sinusoidal movement of the fiber's base by as little as +/-1 nm, corresponding to the application at the bundle's top of a force of +/-0.3 pN, causes detectable phase-locking of the bundle's oscillations to the stimulus. Although entrainment increases as the stimulus grows, the amplitude of the hair-bundle movement does not rise until phase-locking is nearly complete. A bundle is most sensitive to stimulation at its frequency of spontaneous oscillation. Far from that frequency, the sensitivity of an active hair bundle resembles that of a passive bundle. Over most of its range, an active hair bundle's response grows as the one-third power of the stimulus amplitude; the bundle's sensitivity declines accordingly in proportion to the negative two-thirds power of the excitation. This scaling behavior, also found in the response of the mammalian basilar membrane to sound, signals the operation of an amplificatory process at the brink of an oscillatory instability, a Hopf bifurcation.
Hearing relies on active filtering to achieve exquisite sensitivity and sharp frequency selectivity. In a quiet environment, the ears of many vertebrates become unstable and emit one to several tones. These spontaneous otoacoustic emissions, the most striking manifestation of the inner ear's active process, must result from self-sustained mechanical oscillations of aural constituents. The mechanoreceptive hair bundles of hair cells in the bullfrog's sacculus have the ability to amplify mechanical stimuli and oscillate spontaneously. By comparing a hair bundle's spontaneous oscillations with its response to small mechanical stimuli, we demonstrate a breakdown in a general principle of equilibrium thermodynamics, the fluctuation-dissipation theorem. We thus confirm that a hair bundle's spontaneous movements are produced by energy-consuming elements within the hair cell. To characterize the dynamical behavior of the active process, we introduce an effective temperature that, for each frequency component, quantifies a hair bundle's deviation from thermal equilibrium. The effective temperature diverges near the bundle's frequency of spontaneous oscillation. This behavior, which is not generic for active oscillators, can be accommodated by a simple model that characterizes quantitatively the fluctuations of the spontaneous movements as well as the hair bundle's linear response function.
We present the results of the first successful experiments aimed to control in a quasistationary way the magnetic fluctuation dynamics in a reversed field pinch (RFP) device. This is done by the application of an oscillating poloidal electric field to the plasma edge. Although the additional power input is negligible, a stationary positive effect on the electron temperature is obtained. Temperature increases up to 50% over the standard values. This experiment demonstrates that in principle a stationary current profile and magnetic fluctuation control technique is feasible in the RFP.
Glycol ethers are widely used as solvents and are hence liable to be released into the atmosphere where they may contribute to the formation of photochemical air pollution in urban and regional areas. The dominant reaction of glycol ethers in the atmosphere has been previously shown to be with OH radicals. Using a relative rate method, rate constants have been measured at 296+/-2 K for the gas-phase reactions of the OH radical with 1-butoxy-2-propanol [CH3CH2CH2CH2OCH2CH(OH)CH3], diethylene glycol ethyl ether [CH3CH2OCH2CH2OCH2CH2OH], and diethylene glycol n-butyl ether [CH3CH2CH2CH2OCH2CH2OCH2-CH2OH] of (in units of 10(-11) cm3 molecule(-1) s(-1)) 3.76+/-0.54, 5.72+/-0.85, and 7.44+/-0.94, respectively, where the error limits include the estimated overall uncertainties in the rate constants for the reference compounds. Products of the OH radical-initiated reactions of these glycol ethers have been investigated using gas chromatography with flame ionization detection (GC-FID), combined gas chromatography-mass spectrometry (GC-MS), in situ Fourier transform infrared (FT-IR) spectroscopy, and in situ atmospheric pressure ionization tandem mass spectrometry (API-MS). The products identified and quantified account for 102+/-11% of the reaction products from 1-butoxy-2-propanol, 87+/-9% of those from diethylene glycol ethyl ether, and 83+/-12% of those from diethylene glycol n-butyl ether. An empirical estimation method for calculating reaction rates of alkoxy radicals under atmospheric conditions appears to fairly well predict the products formed and their yields. Detailed reaction schemes after the initial OH radical reactions are formulated for each of these glycol ethers, with the majority of the reactions involving H-atom abstraction from the CH2 groups adjacent to the ether linkage.
Various studies have suggested that the rate of adult skin healing may be in some way dependent on signals emanating from cutaneous nerves. Further, it appears that adult wounds become hyperinnervated by sensory nerves during the process of healing. In order to investigate this reciprocal relationship further, we have used a simple embryonic model to look at the effect of wounds on nerves, and conversely, the effect of nerves on wounds. We find that wounds made to the dorsum of the chick wing bud, at a stage prior to normal innervation (at E4), or soon after the normal establishment of cutaneous innervation (at E7), subtly alter the pattern of branching by perturbing developmental guidance cues, but do not cause hyperinnervation, whereas wounding at E14 does cause hyperinnervation. By creating chicks with nerveless wings, we show that from E7, wound healing in the absence of nerves is significantly impaired. These observations suggest that, from the earliest stages of skin innervation, the presence of nerves is beneficial to the healing process, but that, in contrast to neonatal and adult tissues, wound healing in the embryo and early foetus does not trigger hyperinnervation.
Steroidal glycoalkaloids of many Solanum species have recognized biological activities, especially those containing the glycosyl moiety alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-D-glucopyranose (chacotriose) whose peracetate is here synthesized and characterized by complete 1H and 13C NMR assignment.
Recent studies show that the underlying amnioserosa works actively to help bring together the two epithelial sheets and close the embryonic hole during dorsal closure in fruitfly development.
In the endocrine pancreas, alpha-cell-specific expression of the glucagon gene is mediated by DNA-binding proteins that interact with the G1 proximal promoter element. Among these proteins, the paired domain transcription factor Pax-6 has been shown to bind to G1 and to transactivate glucagon gene expression. Close to the Pax-6-binding site, we observed the presence of a binding site for a basic leucine zipper transcription factor of the Maf family. In the present study, we demonstrate the presence of Maf family members in the endocrine pancreas that bind to G1 and transactivate glucagon promoter expression. In transient transfection experiments, we found that the transactivating effect on the glucagon promoter was greatly enhanced by the simultaneous expression of Maf transcription factors and Pax-6. This enhancement on glucagon transactivation could be correlated with the ability of these proteins to interact together but does not require binding of Maf proteins to the G1 element. Furthermore, we found that Maf enhanced the Pax-6 DNA binding capacity. Our data indicate that Maf transcription factors may contribute to glucagon gene expression in the pancreas.
A molecularly imprinted polymer (MIP) material was synthesized for use as an in-tube solid-phase microextraction (SPME) adsorbent. The inherent selectivity and chemical and physical robustness of the MIP material was demonstrated as an effective stationary-phase material for in-tube SPME. An automated and on-line MIP SPME extraction method was developed for propranolol determination in biological fluids. This simplified the sample preparation process and the chromatographic separation of several beta-blocker compounds. The method developed for propranolol showed improved selectivity in comparison to alternative in-tube stationary-phase materials, overcoming the limitations of existing SPME coating materials. Preconcentration of the sample by the MIP adsorbent increased the sensitivity, yielding a limit of detection of 0.32 microg/mL by UV detection. Excellent method reproducibility (RSD < 5.0%) and column reusability (> 500 injections) were observed over a fairly wide linear dynamic range (0.5-100 microg/mL) in serum samples. To our knowledge, this is the first report on the automated application of a MIP material for in-tube SPME. The method was inexpensive, simple to set up, and simplified the choice of SPME adsorbent for in-tube extraction. The approach can potentially be extended to other MIPs for the determination of a wide range of chemically significant analytes.
Triplex forming oligonucleotides (TFOs) are of interest because of their potential for facile gene targeting. However, the failure of TFOs to bind target sequences at physiological pH and Mg(2+) concentration has limited their biological applications. Recently, pyrimidine TFOs with 2'-O-aminoethyl (AE) substitutions were shown to have enhanced kinetics and stability of triplex formation (Cuenoud, B., Casset, F., Husken, D., Natt, F., Wolf, R. M., Altmann, K. H., Martin, P., and Moser H. E. (1998) Angew. Chem. Int. Ed. 37, 1288--1291). We have prepared psoralen-linked TFOs with varying amounts of the AE-modified residues, and have characterized them in biochemical assays in vitro, and in stability and HPRT gene knockout assays in vivo. The AE TFOs showed higher affinity for the target in vitro than a TFO with uniform 2'-OMe substitution, with relatively little loss of affinity when the assay was performed in reduced Mg(2+). Once formed they were also more stable in "physiological" buffer, with the greatest affinity and stability displayed by the TFO with all but one residue in the AE format. However, TFOs with lesser amounts of the AE modification formed the most stable triplexes in vivo, and showed the highest HPRT gene knockout activity. We conclude that the AE modification can enhance the biological activity of pyrimidine TFOs, but that extensive substitution is deleterious.