Invasive group A streptococcal disease in Taiwan is not associated with the presence of streptococcal pyrogenic exotoxin genes

We reviewed the clinical features of 44 patients with invasive group A streptococcal (GAS) disease who were treated at two teaching hospitals in southern Taiwan from 1991 to 1994. Genes encoding streptococcal pyrogenic exotoxin types A (speA), B (speB), C (speC), and F (speF) and serotypes of M1, M6, and M12 were determined by polymerase chain reaction to target specific sequences in the 44 isolates recovered from these patients and in 28 isolates recovered from upper respiratory sites in 28 additional patients during the study period. The protease activity of these isolates was tested by using the casein plate method. Of the 44 patients with invasive diseases, 25 (57%) had no obvious underlying diseases, and 14 (32%) had preexisting neoplastic diseases or had previously used steroids. Twenty-five patients (57%) presented with cellulitis or necrotizing fasciitis, 24 (55%) had bacteremia, and eight (18%) had streptococcal toxic shock syndrome (STSS). Eight patients (18%) died of invasive GAS disease; seven had STSS, and seven had underlying diseases. All eight patients died within 48 hours after hospitalization. The presence of speA, speC, or speF was not implicated in any particular clinical syndrome in patients with invasive GAS disease. High-level protease activity and the M1 serotype of the isolates were significantly associated with the clinical signs of STSS and with mortality. M1 serotype and protease activity, as well as host immune status, might play significant roles in the pathogenesis of invasive GAS disease in Taiwan.     

Thyroid peroxidase: kinetics, pH optima and substrate dependency

The oxidation of iodide, guaiacol and 2,2'-azino-di[3-ethyl-benzthiazoline-(6)-sulphonic acid] and the iodination of tyrosyl residues in bovine serum albumin, catalysed by partly purified thyroid peroxidase, were studied. The enzyme showed pH optima with all electron donors. With the exception of guaiacol, the position of the pH optima depended upon both the electron donor and hydrogen peroxide concentrations. With increased hydrogen peroxide concentrations the optima shifted to lower pH, and with increased iodide concentration to higher pH. For monoiodotyrosine (MIT) formation in bovine serum albumin the position of the pH optimum was also dependent on the hydrogen peroxide concentrations. The position of the pH optimum of the oxidation of guaiacol was pH 9 and independent of substrate and hydrogen peroxide concentrations. It is obvious from these findings that iodination reactions must be studied under well-defined conditions.     

alpha B-crystallin and hsp25 in neonatal cardiac cells--differences in cellular localization under stress conditions

OBJECTIVES: The aim of this study was to determine (a) whether delay in femur fracture stabilization beyond twenty-four hours in patients with head injury increased the risk of pulmonary complications and (b) whether immediate (up to twenty-four hours) femur fracture stabilization increased the risk of central nervous system (CNS) complications. DESIGN: Retrospective analysis. MATERIALS AND METHODS: Thirty-two patients with femur fracture and head injury were identified. Fourteen underwent immediate stabilization of their fractures, and eighteen underwent delayed (four-teen patients) or no (four patients) stabilization of their fractures. RESULTS: In the immediate stabilization group, five patients had severe head injuries [Glasgow Coma Score (GCS) < or = 8] and nine had mild head injuries (GCS > 8). In the mild head injury group, no patient had a pulmonary complication and one had a CNS complication. In the severely head-injured group, one patient had a pulmonary complication and no patient had a CNS complication. In the delayed stabilization group, six patients had mild head injuries (GCS > 8) and twelve had severe head injuries (GCS < or = 8). In the mildly head injured group, one patient had a pulmonary complication, two patients had CNS complications, and one patient died. In the severely head injured group, nine patients had pulmonary complications, three patients had CNS complications, and one patient died. Logistic regression identified delay in femur stabilization as the strongest predictor of pulmonary complication (p = 0.0042), followed by severity of chest Abbreviated Injury Score (AIS; p = 0.0057) and head AIS (p = 0.0133). Delaying fracture stabilization made pulmonary complications forty-five times more likely. Each point increase in the chest AIS and head/neck AIS increased the risk of pulmonary complication by 300 percent and 500 percent, respectively. A statistically significant predictor of CNS complications could not be identified by using logistic regression. CONCLUSION: Delay in stabilization of femur fracture in head-injured patients appears to increase the risk of pulmonary complications. However, due to selection bias in this patient sample, this question cannot be definitively answered. Early fracture stabilization did not increase the prevalence of CNS complications.     

Performance and tissue zinc and metallothionein accumulation in chicks fed a high dietary level of zinc

Four experiments were conducted to identify several factors that might improve the accuracy and reproducibility of Zn bioavailability assays for chicks. Response of tissue Zn and metallothionein (MT) concentrations to various elevated levels and soluble sources of dietary Zn were measured, as well as the effect of delaying high Zn administration until 7 d posthatching to alleviate the detrimental effect of Zn sulfate on feed intake to 3 wk of age. Bone Zn increased (P < 0.01) in all experiments in response to increasing dietary Zn concentrations. Liver and pancreas MT were affected (P < 0.01) by a source by age interaction and variability that made this criterion unsuitable for bioavailability assays. Lastly, 1-d-old chicks were used to study the effect of delaying feeding of a high-Zn diet up to 7 d of age. The basal diet was fed continuously for 21 d as a control. A diet containing 1,000 ppm Zn was either fed continuously from Day 1, or started on Day 3, 5, or 7. Chicks given high Zn on Day 3, 5, or 7 decreased (P < 0.01) feed intake within 24 h of feeding. Delayed feeding of high dietary Zn might help to alleviate decreased feed intake observed in previous studies. Delaying the onset of high Zn feeding by several days may help alleviate feed intake problems observed with Zn sulfate. Use of either Zn gluconate or Zn acetate as a standard in assays or use of MT synthesis as a bioavailability criterion will probably not be useful to improve accuracy of the estimates.     

Growth, voluntary food intake and digestion in farmed temperate and tropical deer

Growth and voluntary feed intake (VFI) in grazing temperate farmed deer species are influenced by the feeding value of the forage and the stage of the deer's seasonal cycle. Liveweight gain (LWG) of growing red deer was greater when perennial ryegrass (0.80)/white clover (0.20) pasture was grazed at 10 cm than 5 cm surface height, but venison production by one year of age was still low. Chicory and red clover were of superior feeding value for deer than perennial ryegrass-based pastures, increasing LWG of young red and hybrid (0.25 elk; 0.75 red deer) deer during summer and autumn, due to higher VFI and to higher organic matter digestibility. Relative to perennial ryegrass, chicory disintegrated faster in the rumen, with very low rumination time and faster rumen outflow rates of liquid and particulate matter. Inputs of red clover and chicory substantially increased venison carcass weights at one year of age from grazing red and hybrid stags. In indoor pen feeding studies, red deer were shown to have a seasonal cycle of digestive function, with greater rumen mean retention time (MRT) and greater rates of rumen ammonia production in summer than in winter. It was deduced that the purpose of the digestive cycle was to maintain apparent digestibility constant as VFI increased during summer. Tropical sambar deer were also shown to have seasonal cycles in growth and VFI that were of reduced amplitude compared with red deer. Peak VFI and growth occurred in autumn and minimum VFI and growth occurred in spring. Feed conversion (kg DM eaten/kg LWG) was more efficient for sambar than for red deer, due to lower VFI and lower heat production, but there was no difference between species in digestive efficiency.     

Pharmacology and subcellular distribution of [3H]rilmenidine binding sites in rat brain

We have previously reported that in rat brain membranes, [3H]rilmenidine, in addition to labelling alpha2-adrenoceptors and the I2B-subtype of imidazoline receptor binding site (I2B-RBS), may label an additional I-RBS population, distinct from previously classified I1-RBS and I2-RBS. In this study, using crude or fractionated rat brain membranes we examined the possible association of [3H]rilmenidine-labelled I-RBS with the A- and B-isoforms of monoamine oxidase (MAO) by studying the inhibition of [3H]rilmenidine binding by a number of MAO inhibitors; and comparing the maximal binding density (Bmax) and subcellular distribution of [3H]rilmenidine binding sites with that of MAO-A and MAO-B catalytic sites labelled by [3H]RO41-1049 and [3H]RO19-6327 and 12-RBS labelled by [3H]2-BFI. Inhibition of [3H]rilmenidine binding by all MAO inhibitors tested produced very shallow curves (slope 0.29-0.56). Clorgyline and moclobemide (selective MAO-A inhibitors) displayed moderate affinities (60-140 nM), while pargyline (non-selective MAO-inhibitor), RO41-1049 (selective MAO-A inhibitor) and RO19-6327 (selective MAO-B inhibitor) exhibited very low affinities (> 2 microM) for 50-75% of [3H]rilmenidine-labelled I-RBS in crude brain membranes and even lower affinity for the remaining binding. Under identical buffer conditions, the Bmax of [3H]rilmenidine-labelled I-RBS (1.45+/-0.14 pmol/mg protein) was considerably lower than those of MAO-A (13.10+/-0.15 pmol/mg) and MAO-B (10.35+/-0.50 pmol/mg) sites. These results suggest that [3H]rilmenidine does not interact directly with the active catalytic site of either MAO enzyme and could at best only associate with a subpopulation of MAO molecules. Binding studies on five fractions of rat cortex homogenates-nuclear (N), heavy (M) and light (L) mitochondrial, microsomal non-mitochondrial (P), and soluble cytosolic (S) fractions-revealed that 45% of total [3H]rilmenidine binding was present in the P fraction cf. 20 and 23% in the M and L fractions, in contrast to [3H]RO19-6327 and [3H]2-BFI which bound 11-13% in the P fraction and 36-38% and 35-44% in the M and L fractions, respectively. Binding of all ligands in the N fraction was 6-15% of total. These studies reveal that [3H]rilmenidine-labelled I-RBS, unlike the I2-RBS, are not predominantly associated with mitochondrial fractions containing the MAO enzymes (and cytochrome oxidase activity), but appear to be distributed in both the mitochondrial and plasma membrane fractions in rat cerebral cortex.     

Sugar-induced molten-globule model

Proteins denature at low pH because of intramolecular electrostatic repulsions. The addition of salt partially overcomes this repulsion for some proteins, yielding a collapsed conformation called the A-state. A-states have characteristics expected for the molten globule, a notional kinetic protein folding intermediate. Here we show that the addition of neutral sugars to solutions of acid-denatured equine ferricytochrome c induces formation of the A-state in the absence of added salt. We characterized the structure and stability of the sugar-induced A-state with circular dichroism spectropolarimetry (CD) and NMR-monitored hydrogen-deuterium exchange experiments. We also examined the stability of the sugar-induced A-state as a function of sugar size and concentration. The results are interpreted using several models and we conclude that the stabilizing effect is consistent with increased steric repulsion between the protein and the sugar solutions.     

Respiratory syncytial virus (RSV) disease and prospects for its control

Respiratory syncytial virus (RSV) is a major virus pathogen of infants and young children, an important cause of disease in adults and is responsible for a significant amount of excess morbidity and mortality in the elderly. It also can be devastating in immunosuppressed populations. Vaccines are being developed, but none are currently licensed. Moreover, even if one or more are approved, they may not be suitable for some populations vulnerable to RSV (e.g. very young infants and the immunosuppressed). Ribavirin and immunoglobulin preparations with high titers of RSV-specific neutralizing antibodies are currently approved for use to treat and prevent RSV infection. However, neither of these is cost-effective or simple to administer. New agents are needed to reduce the impact of RSV. This review is concerned with the means currently available for controlling RSV, the search for new agents effective against this virus, and future prospects for preventing and treating RSV infections.