Mycobacterium tuberculosis infection of end-stage renal disease patients in Taiwan: a nationwide longitudinal study.

End-stage renal disease (ESRD) patients are vulnerable to Mycobacterium tuberculosis (MTB) infection, but the magnitude of the risk is uncertain. In addition, there is no reliable information on the MTB infection rate of patients undergoing different types of renal replacement therapy (RRT). We used the Taiwan National Health Insurance Research Database to conduct a 9-year nationwide longitudinal study. Among 49 983 ESRD patients who received three renal replacement modalities, there were 562 cases of MTB infection, corresponding to an incidence rate of 3.0 per 1000 patient-years. The risk of MTB infection relative to the general population was 4.5. Multivariate Cox regression analysis indicated that the independent risk factors for MTB infection in ESRD patients are old age (hazard ratio (HR) 1.17 per 10 years, p <0.001), male gender (HR 1.37, p <0.001), silicosis (HR 5.82, p <0.001), and chronic obstructive pulmonary disease (HR 1.68, p 0.012). Hyperlipidaemia (HR 0.71, p <0.001) and hypertension (HR 0.81, p 0.05) are associated with a lower infection rate. There was no effect of RRT modality on MTB infection rate.

Impact of positive end-expiratory pressure during heterogeneous lung injury: insights from computed tomographic image functional modeling.

Image Functional Modeling (IFM) synthesizes three dimensional airway networks with imaging and mechanics data to relate structure to function. The goal of this study was to advance IFM to establish a method of exploring how heterogeneous alveolar flooding and collapse during lung injury would impact regional respiratory mechanics and flow distributions within the lung at distinct positive end-expiratory pressure (PEEP) levels. We estimated regional respiratory system elastance from computed tomography (CT) scans taken in 5 saline-lavaged sheep at PEEP levels from 7.5 to 20 cmH(2)O. These data were anatomically mapped into a computational sheep lung model, which was used to predict the corresponding impact of PEEP on dynamic flow distribution. Under pre-injury conditions and during lung injury, respiratory system elastance was determined to be spatially heterogeneous and the values were distributed with a hyperbolic distribution in the range of measured values. Increases in PEEP appear to modulate the heterogeneity of the flow distribution throughout the injured lung. Moderate increases in PEEP decreased the heterogeneity of elastance and predicted flow distribution, although heterogeneity began to increase for PEEP levels above 12.5-15 cmH(2)O. By combining regional respiratory system elastance estimated from CT with our computational lung model, we can potentially predict the dynamic distribution of the tidal volume during mechanical ventilation and thus identify specific areas of the lung at risk of being overdistended.

Skeletal muscle ECF pH error signal for exercise ventilatory control.

An autonomic reflex linking exercising skeletal muscle metabolism to central ventilatory control is thought to be mediated by neural afferents having free endings that terminate in the interstitial fluid of muscle. To determine whether changes in muscle extracellular fluid pH (pHe) can provide an error signal for exercise ventilatory control, pHe was measured during electrically induced contraction by 31P-magnetic resonance spectroscopy and the chemical shift of a phosphorylated, pH-sensitive marker that distributes to the extracellular fluid (phenylphosphonic acid). Seven lightly anesthetized rats underwent unilateral continuous 5-Hz sciatic nerve stimulation in an 8.45-T nuclear magnetic resonance magnet, which resulted in a mixed lactic acidosis and respiratory alkalosis, with no net change in arterial pH. Skeletal muscle intracellular pH fell from 7.30 +/- 0.03 units at rest to 6.72 +/- 0.05 units at 2.4 min of stimulation and then rose to 7.05 +/- 0.01 units (P < 0.05), despite ongoing stimulation and muscle contraction. Despite arterial hypocapnia, pHe showed an immediate drop from its resting baseline of 7.40 +/- 0.01 to 7.16 +/- 0.04 units (P < 0.05) and remained acidic throughout the stimulation protocol. During the on- and off-transients for 5-Hz stimulation, changes in the pH gradient between intracellular and extracellular compartments suggested time-dependent recruitment of sarcolemmal ion-transport mechanisms. pHe of exercising skeletal muscle meets temporal and qualitative criteria necessary for a ventilatory metaboreflex mediator in a setting where arterial pH does not.

Molecular cloning and sequencing of cDNAs encoding insecticidal peptides from the primitive hunting spider, Plectreurys tristis (Simon).

Plectreurys tristis cephalothorax mRNA was isolated and amplified by PCR using degenerate primers corresponding to reverse translated mature Plt-VI toxin. An oligonucleotide corresponding to a portion of the amplified product was then used to screen a P. tristis cDNA library. The cDNAs from 10 positive clones were sequenced. Eight of these cDNAs corresponded to Plt-VI toxin, one to Plt-XI toxin, and one was very similar to Plt-VIII toxin, with the exception of a single amino acid substitution. Analysis of these cDNAs indicated that these toxins are initially synthesized as prepro-forms which undergo signal cleavage followed by additional processing at both their N- and C-termini to produce the mature products.

Comparative metabolism of branched-chain amino acids to precursors of juvenile hormone biogenesis in corpora allata of lepidopterous versus nonlepidopterous insects.

Comparative studies were performed on the role of branched-chain amino acids (BCAA) in juvenile hormone (JH) biosynthesis using several lepidopterous and nonlepidopterous insects. Corpora cardiaca-corpora allata complexes (CC-CA, the corpora allata being the organ of JH biogenesis) were maintained in culture medium containing a uniformly 14C-labeled BCAA, together with [methyl-3H]methionine as mass marker for JH quantification. BCAA catabolism was quantified by directly analyzing the medium for the presence of 14C-labeled propionate and/or acetate, while JHs were extracted, purified by liquid chromatography, and subjected to double-label liquid scintillation counting. Our results indicate that active BCAA catabolism occurs within the CC-CA of lepidopterans, and this efficiently provides propionyl-CoA (from isoleucine or valine) for the biosynthesis of the ethyl branches of JH I and II. Acetyl-CoA, formed from isoleucine or leucine catabolism, is also utilized by lepidopteran CC-CA for biosynthesizing JH III and the acetate-derived portions of the ethyl-branched JHs. In contrast, CC-CA of nonlepidopterans fail to catabolize BCAA. Consequently, exogenous isoleucine or leucine does not serve as a carbon source for the biosynthesis of JH III by these glands, and no propionyl-CoA is produced for genesis of ethyl-branched JHs. This is the first observation of a tissue-specific metabolic difference which in part explains why these novel homosesquiterpenoids exist in lepidopterans, but not in nonlepidopterans.

Sources of propionate for the biogenesis of ethyl-branched insect juvenile hormones: Role of isoleucine and valine.

Corpora allata from adult female Manduca sexta biosynthesize the sesquiterpenoid juvenile hormone (JH) III and the unusual ethyl-branched homologue JH II in vitro. We maintained corpora allata in medium 199 using [methyl-(3)H]methionine as the source of the JH methyl ester moiety and as a mass marker. This allowed measurement of the relative contributions of (14)C-labeled precursors to the biogenesis of JH II and III carbon skeletons. We showed efficient incorporation of a propionate equivalent, from isoleucine or valine catabolism, into the ethyl-branched portion of JH II, using double-label liquid scintillation counting of isolated JHs and gas chromatography/mass spectrometry with selected ion monitoring of JH deuteromethoxyhydrin derivatives. Methionine was a poor source of propionate for JH II biosynthesis, while glucose, succinate, threonine, and beta-alanine did not contribute propionate at all. Leucine, isoleucine, and glucose incorporated into JH III and the acetate-derived portion of JH II.

Identification of a juvenile hormone-like compound in a crustacean.

Juvenile hormone (JH) has central roles in the regulation of insect development and reproduction but has not previously been identified in other arthropod classes. The hemolymph of a crustacean, Libinia emarginata (Leach), has now been analyzed for JH-like compounds. Samples contained 0.003 to 0.030 nanogram of JH III per milliliter and 10 to 50 nanograms of methyl farnesoate per milliliter; methyl farnesoate is a compound structurally related to JH III that has JH bioactivity. Several tissues were examined for synthesis and secretion of JH-like compounds. Of these tissues, only the mandibular organs produced and secreted JH III and methyl farnesoate. However, microchemical analysis revealed that this JH III was racemic, and thus likely an artifactual oxidation product of methyl farnesoate. Secretion of methyl farnesoate was related to reproduction in females, with the highest rates observed in Libinia near the end of the ovarian cycle when oocyte growth and vitellogenesis are greatest. These results indicate that JH-like compounds such as methyl farnesoate have regulatory roles in crustaceans.

Detection of only JH III in several life-stages of Nauphoeta cinerea and Thermobia domestica.

We have conducted a reinvestigation into both the identification and quantification of juvenile hormone (JH) from several developmental stages of the cockroach, Nauphoeta cinerea, and the firebrat, Thermobia domestica, using a gas chromatography-mass spectrometric (GC/MS) method. We detected only JH III in these animals in contrast to prior studies in which JH I, II, and/or III had been reported using a different scheme relying on HPLC purification and subsequent GC/MS analysis under chemical ionization (CI) conditions. Very high levels (approximately 800 ng/g) of JH III were found in N. cinerea embryos at stages after dorsal closure whereas first stadium nymphs and female penultimate stadium nymphs contained only low levels (approximately 1 ng/g and approximately 7 ng/ml respectively); in adult females at the stage of rapid oocyte growth approximately 150 ng JH III per ml of hemolymph was measured. T. domestica nymphs and egg laying adults contained only low levels (approximately 1 ng/g) of JH III. The results emphasize the caution which must be used in interpreting results of procedures for analysis of JH at parts-per-billion levels, and also enforce prior observations that the higher JH homologs are not present except in the Lepidoptera.

Farnesol and farnesal dehydrogenase(s) in corpora allata of the tobacco hornworm moth, Manduca sexta.

The metabolism of [3H]farnesol was studied in cell-free preparations of corpora allata from the tobacco hornworm, Manduca sexta, to assess the role of this presumed biosynthetic precursor of juvenile hormone (JH) III. A reversed-phase ion-pair liquid chromatographic (RP-IPC) procedure was devised to separate farnesol from several potential intermediates in its presumed metabolism to JH III: farnesal, farnesoic acid, 10,11-epoxyfarnesoic acid, and methyl farnesoate. Following incubation of (2E,6E)-[1,5,9-3H]farnesol with homogenates of corpora allata from fifth instar larvae or adult female M. sexta, and analysis by RP-IPC, the major radiolabeled products corresponded to farnesoic acid, farnesal, and a polar product(s) presumably derived from the tritium on C-1 of farnesol. Inclusion of NAD+ in the incubations conducted with crude homogenates resulted in enhanced [3H]farnesol metabolism, decreased accumulation of [3H]farnesal, and increased levels of [3H]farnesoic acid. Substitution of NADP+ for NAD+ was ineffective, suggesting that farnesol and/or farnesal dehydrogenase were NAD+-dependent enzymes. Pellet fractions obtained by differential centrifugation of crude homogenates exhibited both farnesol and farnesal dehydrogenase activity but only the latter was clearly stimulated by addition of NAD+. The alcohol/aldehyde dehydrogenase(s) showed some substrate specificity for the 2E isomer; nerol and (2Z,6E)-farnesol were barely metabolized under conditions in which either geraniol or (2E,6E)-farnesol were rapidly oxidized. The identity of the [3H]farnesal zone obtained from RP-IPC was further established by normal-phase liquid chromatography and by gas-liquid chromatography-mass spectrometry.(ABSTRACT TRUNCATED AT 250 WORDS)