Modelling study of IgE/receptor interactions

Models of the lectin-homology domains of the human and murine low-affinity receptors for IgE (Fc epsilon RII/CD23) were built on the basis of sequence similarity with rat mannose-binding protein, the structure of which is known. The sites on Fc epsilon RII/CD23 that are possibly involved in the interaction with IgE and with another ligand, CD21/CR2, are proposed. The models may assist the design of protein engineering experiments for the study of the reactivity of these molecules.     

Effects of prenatal androgenization, melengestrol acetate, and Synovex-H on feedlot performance, carcass, and sensory traits of once-calved heifers

Three studies were designed using a 2 x 2 factorial arrangement of treatments within each experiment to evaluate the effects of various management techniques on growth and carcass traits of once-calved heifers. In Exp. 1, 33 yearling (16 control [C] and 17 prenatally androgenized [PA]) and 39 once-calved (20 C and 19 PA) nonpregnant heifers were used to evaluate the effects of age and PA. Once-calved heifers were approximately 31 kg heavier (P < .03) on-test, initially consumed 11% more (P < .01) DM, and gained 11% faster (P < .08), but had similar (P = .44) gain to feed ratios (.138 vs. .131) as yearlings. Growth performance was not affected by PA. The yearling and once-calved heifers were then slaughtered at approximately 707 and 1,080 d of age, respectively. Despite maturity differences (P < .01), marbling scores (P = .26) and percentage of choice carcasses (P = .27) were similar. However, on the basis of newly accepted grading changes, percentage of once-calved heifer carcasses grading choice decreased from 57.3 to 34.4%. Organoleptic properties did not differ. Experiments 2 and 3 were then conducted to evaluate effects of commercially available products (melengestrol acetate [MGA] and Synovex-H) on feedlot characteristics of heifers following weaning of their first calf. In Exp. 2, 48 once-calved Simmental-based heifers were fed during the summer to a constant compositional fat thickness of .8 cm. Experiment 3 was conducted in the late fall and early winter, during which 52 moderately sized heifers were fed for 116 d postweaning and slaughtered. Performance of heifers in Exp. 2 was not affected by MGA. However, heifers fed MGA in Exp. 3 gained 9% faster (P < .05) than controls. In Exp. 2, Synovex-H tended to improve ADG (P < .09) and feed efficiency (P < .07), but did not affect performance in Exp. 3. Most carcass traits were not affected by either treatment. Nonpregnant, once-calved heifers seem to have a large capacity for efficient weight gain as compared with yearling heifers. However, hormonal compounds, such as testosterone propionate provided pre- or postnatally (Synovex-H), and MGA do not appear to provide the consistent, positive responses often seen with younger, more typical feedlot heifers.     

Liver transplantation. Who should be referred--and when?

Orthotopic liver transplantation is a highly effective treatment for patients with end-stage cirrhosis. At most centers, 5-year survival rates are about 85%. However, donor organs continue to be in short supply, and the issue of patient selection has become increasingly important. The primary care physician plays an important role in referring the patient early--before irreversible complications arise.     

Posterior fossa decompression without duraplasty in infants and young children for treatment of Chiari malformation and achondroplasia

Some children with Chiari malformation and achondroplasia require posterior fossa decompression that typically includes expansion of the dural tube with duraplasty. Infants and young children, however, may have a more distensible dura mater than do older patients. Furthermore, the structures that compress the hindbrain of young patients may be the bone and abnormally thickened atlantooccipital membrane, i.e., dural band, rather than the dura mater. We have treated 7 children who had Chiari malformation or achondroplasia with posterior fossa decompression without duraplasty. All children were symptomatic; 3 had Chiari-I malformations, 2 Chiari-II malformations, and 2 achondroplasia. The age range was 3 months to 2.5 years (mean 15.1 months). The exent of tonsillar herniation and other hindbrain anomalies was assessed on preoperative magnetic resonance imaging. The infants with Chiari-II malformations underwent cervical laminectomies, whereas the other young children with Chiari-I malformations or achondroplasia underwent suboccipital craniectomy as well as cervical laminectomy. In Chiari malformation, the dural band was divided; in achondroplasia, there was no identifiable dural band. Following bony decompression and division of the identifiable dural band, immediate expansion of the stenotic region with visible cerebrospinal fluid space posterior to the neural elements could be ascertained by intraoperative ultrasonography. During a follow-up period ranging from 4.5 months to 4 years (mean 22 months), all patients made improvements in their symptoms, 3 having complete resolution of their symptoms. This preliminary experience indicates that in children 2 years of age or younger, posterior fossa bony decompression without duraplasty can be effective treatment for Chiari malformations or achondroplasia.     

On the reaction mechanism of L-lactate oxidase: quantitative structure-activity analysis of the reaction with para-substituted L-mandelates

The rate constants for reduction of the flavoenzyme, L-lactate oxidase, and a mutant (in which alanine 95 is replaced by glycine), by a series of para-substituted mandelates, in both the 2-1H- and 2-2H- forms, have been measured by rapid reaction spectrophotometry. In all cases, significant isotope effects (1H/2H = 3-7) on the rate constants of flavin reduction were found, indicating that flavin reduction is a direct measure of alpha-C-H bond breakage. The rate constants show only a small influence of the electronic characteristics of the substituents, but show a good correlation when combined with some substituent volume parameters. A surprisingly good correlation is found with the molecular mass of the substrate. The results are compatible with any mechanism in which there is little development of charge in the transition state. This could be a transfer of hydride to the flavin N(5) position or a synchronous mechanism in which the alpha-C-H is formally abstracted as a H+ while the resulting charge is simultaneously neutralized by another event.     

Inhibition by propofol (2,6 di-isopropylphenol) of the N-methyl-D-aspartate subtype of glutamate receptor in cultured hippocampal neurones

1. The effects of propofol (2,6 di-isopropylphenol) on responses to the selective glutamate receptor agonists, N-methyl-D-aspartate (NMDA) and kainate, were investigated in cultured hippocampal neurones of the mouse. Whole cell and single channel currents were recorded by patch-clamp techniques. Drugs were applied with a multi-barrel perfusion system. 2. Propofol produced a reversible, dose-dependent inhibition of whole cell currents activated by NMDA. The concentration of propofol which induced 50% of the maximal inhibition (IC50) was approximately 160 microM. The maximal inhibition was incomplete leaving a residual current of about 33% of the control response. This inhibitory action of propofol was neither voltage- nor use-dependent. 3. Analysis of the dose-response relation for whole cell NMDA-activated currents indicated that propofol caused no significant change in the apparent affinity of the receptor for NMDA. 4. Outside-out patch recordings of single channel currents evoked by NMDA (10 microM) revealed that propofol (100 microM) reversibly decreased the probability of channel opening but did not influence the average duration of channel opening or single channel conductance. 5. Whole-cell currents evoked by kainate (50 microM) were insensitive to propofol (1 microM-1 mM). 6. These results indicate that propofol inhibits the NMDA subtype of glutamate receptor, possibly through an allosteric modulation of channel gating rather than by blocking the open channel. Depression of NMDA-mediated excitatory neurotransmission may contribute to the anaesthetic, amnesic and anti-convulsant properties of propofol.     

CsA, FK506, corticosteroids and rapamycin inhibit TNF alpha production by cultured PTEC

In this study we investigated the effect of immunosuppressive drugs on the interleukin-1 alpha (IL-1 alpha) enhanced tumor necrosis factor alpha (TNF alpha) production by proximal tubular epithelial cells (PTEC). Under basal conditions cultured PTEC produce between 0 to 390 pg/ml/10(5) cells of TNF alpha. Upon stimulation with IL-1 alpha an enhancement of TNF alpha production was seen in each cell line tested, ranging from 230 to 2424 pg/ml/10(5) cells. The presence of cyclosporin A (CsA) during stimulation with IL-1 alpha inhibited the enhanced TNF alpha production in a dose dependent fashion, with a maximal inhibition of 90% at a concentration of 250 ng/ml. Inhibition was at the level of mRNA as could be demonstrated by Northern blot analysis. FK506, corticosteroids and rapamycin also inhibited TNF alpha production in a dose dependent fashion, although not as effectively as CsA. Two corticosteroids were tested for their inhibitory effect on TNF alpha production. It was found that dexamethasone at a concentration of 10 ng/ml inhibited TNF alpha production for almost 40%. A 100-fold higher concentration of hydrocortisone was necessary to yield similar inhibition. The effect of rapamycin on the IL-1 alpha enhanced TNF alpha production differed from the effect of CsA. While CsA induced a maximal inhibition of 90%, rapamycin only induced a maximal inhibition of 37%, and even less inhibition at higher concentrations of the drug. The presence of the various drugs was essential for their inhibitory effect, because removal of the drug from the PTEC by washing immediately resulted in loss of inhibition. Combinations of CsA and FK506 or rapamycin were not additive.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coordinated strategies for controlling micronutrient malnutrition: a technical workshop

Participants in a November 1991 workshop concluded that coordinated strategies for controlling malnutrition due to iodine, iron, vitamin A and other micronutrients deficiencies are technically feasible and should be given consideration in planning control efforts. Coordinated surveys involving clinical, biochemical and dietary assessment of multiple micronutrients are feasible. Multiple fortification is also possible using such vehicles as salt, processed rice or sugar. Supplementation efforts can be integrated with existing health care programs. Food-based strategies are also effective. The best examples have been community-based and have included a strong nutrition and health education component designed to change food consumption patterns, improve food preservation and preparation practices, and link income-generating activities with food production activities. Successful coordinated efforts will require a strong political commitment and a supportive infrastructure. Specific recommendations include the formation of national coordinating bodies for micronutrient deficiency control, establishment of a micronutrient information network and expansion of technical exchange and training.