Bis(1,3-dibenzyl-imidazolium) µ-oxido-bis-[trichloridoferrate(III)].

In the title compound (C(17)H(17)N(2))(2)[Fe(2)Cl(6)O], obtained from the solid-state reaction of FeCl(2) and N,N'-dibenzyl-imidazolium chloride, the complex anion has approximate D(3d) symmetry with crystallographically imposed inversion symmetry coincident with the bridging µ-O atom. The stereochemistry about each FeCl(3)O centre is distorted tetra-hedral [Fe-Cl = 2.2176 (5)-2.2427 (5) Šand Fe-O = 1.7545 (2) Å]. The Cl atoms are involved in weak anion-cation C-H⋯Cl inter-actions, giving a network structure.

Proptosis--an uncommon presentation of orbital metastases secondary to prostate cancer.

We report the case of a man with advanced prostate cancer who presented as an emergency with proptosis of his right eye. Cross-sectional imaging of his head confirmed the cause to be orbital metastases secondary to his prostate cancer. The patient responded well to treatment with dexamethasone and palliative orbital radiotherapy.

EPR and NMR spectroscopic studies of [MoL2(MeC identical to CMe)Cp]z (L = P-donor ligand, z = 0 and 1): fluxionality in a metal-alkyne redox pair.

Variable temperature NMR and EPR spectroscopic studies provide rates and activation parameters for alkyne rotation and oscillation, respectively, in the fluxional redox pair [Mo(P(OMe)3)2(MeC identical to CMe)Cp][BF4] (diamagnetic) and [Mo(P(OMe)3)2(MeC identical to CMe)Cp] (paramagnetic).

Deletion of a single hydrogen bonding atom from the MS2 RNA operator leads to dramatic rearrangements at the RNA-coat protein interface.

The MS2 coat protein binds specifically to an RNA hairpin formed within the viral genome. By soaking different RNA fragments into crystals of MS2 coat protein capsids it is possible to determine the X-ray structure of the RNA-protein complexes formed. Here we present the structure to 2.85 A resolution of a complex between a chemically modified RNA hairpin variant and the MS2 coat protein. This RNA variant has a substitution at the -5 base position, which has been shown previously to be pyrimidine-specific and is a uracil in the wild-type RNA. The modified RNA hairpin contains a pyridin-4-one base (4one) at this position that lacks the exocyclic 2-oxygen eliminating the possibility of forming a hydrogen bond to asparagine A87 in the protein. The 4one complex structure shows an unprecedented major conformational change in the loop region of the RNA, whereas there is almost no change in the conformation of the protein.

RNA aptamers for the MS2 bacteriophage coat protein and the wild-type RNA operator have similar solution behaviour.

We have probed the effects of altering buffer conditions on the behaviour of two aptamer RNAs for the bacterio-phage MS2 coat protein using site-specific substitution of 2'-deoxy-2-aminopurine nucleotides at key adenosine positions. These have been compared to the wild-type operator stem-loop oligonucleotide, which is the natural target for the coat protein. The fluorescence emission spectra show a position and oligonucleotide sequence dependence which appears to reflect local conformational changes. These are largely similar between the differing oligonucleotides and deviations can be explained by the individual features of each sequence. Recognition by coat protein is enhanced, unaffected or decreased depending on the site of substitution, consistent with the known protein-RNA contacts seen in crystal structures of the complexes. These data suggest that the detailed conformational dynamics of aptamers and wild-type RNA ligands for the same protein target are remarkably similar.

Secondary structure mapping of an RNA ligand that has high affinity for the MetJ repressor protein and interference modification analysis of the protein-RNA complex.

The secondary structure of an RNA aptamer, which has a high affinity for the Escherichia coli MetJ repressor protein, has been mapped using ribonucleases and with diethyl pyrocarbonate. The RNA ligand is composed of a stem-loop with a highly structured internal loop. Interference modification showed that the bases within the internal loop, and those directly adjacent to it, are important in the binding of the RNA ligand to MetJ. Most of the terminal stem-loop could be removed with little effect on the binding. Ethylation interference suggests that none of the phosphate groups are absolutely essential for tight binding. The data suggest that the MetJ binding site on the aptamer is distinct from that of the natural DNA target, the 8-base pair Met box.

Crystal structures of a series of RNA aptamers complexed to the same protein target.

We have determined the crystal structures, at 2.8 A resolution, of two different RNA aptamers, each bound to MS2 coat protein. One of the aptamers contains a non-Watson-Crick base pair, while the other is missing one of the unpaired adenines that make sequence-specific contacts in the wild-type complex. Despite these differences, the RNA aptamers bind in the same location on the protein as the wild-type translational operator. Comparison of these new structures with other MS2-RNA complexes allows us to refine further the definition of the minimal recognition elements and suggests a possible application of the MS2 system for routine structure determination of small nucleic acid motifs.

The roles of the conserved pyrimidine bases in hammerhead ribozyme catalysis: evidence for a magnesium ion-binding site.

We report details of the synthesis and characterization of oligoribonucleotides containing 4-thiouridine or 2-pyrimidinone ribonucleoside (4HC). We have used these probes to examine the roles of the conserved pyrimidines in the central core of the hammerhead ribozyme. The effects on catalysis of singly-substituted hammerhead ribozyme and substrate strands were quantified in multiple-turnover reactions. Various effects were observed on kcat. and Km, with up to a 7-fold decrease and a 3-fold increase respectively. For substitutions with 4HC at positions 3 or 17, catalytic activity in single turnover reactions can be increased up to 8-fold equivalent to 40% of wild-type activity, by increasing the concentration of the Mg2+ cofactor, implying that these substitutions had a deleterious effect on Mg2+ binding. Calculations of the change in the apparent free energy of binding for variants at positions 3, 4 or 17 are each consistent with deletion of a single hydrogen-bond to an uncharged group in the ribozyme. The cytidine 5' to the scissile phosphate had not previously been thought to play a direct role in catalysis, however, removal of the exocyclic amino group decreased kcat. 4-fold. Recently, the crystal structures of a hammerhead ribozyme bound to either a non-cleavable 2'-deoxy substrate strand or a ribo-substrate strand have been reported. The kinetic properties of the variants described here are consistent with several key interactions seen in the crystals, in particular they provide experimental support for the assignment of the proposed catalytically active magnesium ion-binding site.

Probing sequence-specific RNA recognition by the bacteriophage MS2 coat protein.

We present the results of in vitro binding studies aimed at defining the key recognition elements on the MS2 RNA translational operator (TR) essential for complex formation with coat protein. We have used chemically synthesized operators carrying modified functional groups at defined nucleotide positions, which are essential for recognition by the phage coat protein. These experiments have been complemented with modification-binding interference assays. The results confirm that the complexes which form between TR and RNA-free phage capsids, the X-ray structure of which has recently been reported at 3.0 A, are identical to those which form in solution between TR and a single coat protein dimer. There are also effects on operator affinity which cannot be explained simply by the alteration of direct RNA-protein contacts and may reflect changes in the conformational equilibrium of the unliganded operator. The results also provide support for the approach of using modified oligoribonucleotides to investigate the details of RNA-ligand interactions.

Probing the details of the HIV-1 Rev-Rev-responsive element interaction: effects of modified nucleotides on protein affinity and conformational changes during complex formation.

The solution structure of the human immunodeficiency virus type 1 (HIV-1) Rev-responsive element (RRE) has been investigated by enzymic and chemical structural probing of a 71 nt RRE transcript. The minimum sequence information required to maintain recognition by the Rev protein has previously been mapped to a 29 nt stem-loop structure, known as minSLIIB. The key recognition target is a single-stranded RNA bubble at the base of the RNA stem. The fine details of RNA recognition have been probed using chemically synthesized minSLIIBs containing variant base or sugar residues at sites within the bubble. These have been analysed by gel retardation assays and their relative affinities for Rev protein determined. Complex formation between the wild-type minSLIIB RRE and Rev protein was also monitored using CD spectroscopy, which suggests a change in RNA conformation upon Rev binding. The spectral change is consistent with localized melting of RNA, leading to a decrease in the level of base stacking and/or a change in base tilting, during formation of the complex. Deoxynucleotide substitutions on just one side, the 5' side, of the bubble inhibit the conformational change detected by CD. The data are consistent with a dynamic interaction between Rev and its target site. The contact points between Rev and the RRE were probed directly using photo-cross-linking with either ribo-5-bromouridine- or ribo-4-thiouridine-substituted minSLIIBs. The data are consistent with protein-RNA contacts at the bottom of the bubble.

Midwifery in Jordan.

Jordanian midwives, particularly those working in the public sector, are the major health care providers for mothers and their young children. Many women, however, do not receive early prenatal care, and some receive no prenatal care at all. Because of persistent high rates of maternal and early childhood morbidity and mortality, the Minister of Health has identified advanced preparation in primary health care nursing as a priority for some midwives, who will then be expected to function as leaders in the movement toward universal primary health care.

PIP: The Jordan Ministry of Health supports midwifery training and practice because of high maternal and child mortality in Jordan. A national priority in primary health care is the development of midwifery leaders; quality assurance evaluations are considered necessary for attaining optimum health outcomes for all mothers and children. In 1991 about 90% of Sunni Muslims in Jordan have available health services comprised of 6365 physicians, 2426 professional nurses, 4183 practical nurses, and 725 midwives. About 45% of citizens receive health care from public services, 40% from the military sector, and 15% private care. The roles of women have expanded since the 1950s due to increased educational and work opportunities. Woman's role in the family is affected by socioeconomic status. The birth rate in 1992 was 39.5/1000, and infant mortality was 44/1000 live births. Population growth was 3.4%. Marriage and first births occur at young ages and birth intervals are short. 45% are married by the age of 17 years and 50% had 6 or more children. 25% of women gave birth within 18 months of the preceding birth, and 50% gave birth within 2 years. 44% of the population is aged 0-14 years. Major health problems are maternal mortality, premature birth, low birth weight, and infant mortality. Due to government investment in health infrastructure, by 1986 80% of the population was within 10 km of a health center. Services are free of charge to government employees and the poor. In 1983, the most recent year when data was available, about 42% of women did not receive prenatal care and 30% of those with care had only 4 or less visits. Modesty, modesty toward male physicians, and religious belief in God as the best source of good health are obstacles to acceptance of health care. Midwife education is available from the Ministry of Health in a 27 month diploma program; a 6 month training programs is available to "dayas" and a 9 month post-basic training course is available to nurses. Licensing is performed by a professional organization. Program evaluation recommends more and better training of midwives and development of standards of training.

First and second cycle egg production characteristics in commercial table egg flocks.

Egg production data for 1,231 first cycle and 887 second cycle commercial table egg layer flocks were studied to determine the shape of the production curve, the relationship between the two cycles, and the effects of strain and season on various measures of egg production. Means for peak egg production were 89.1 and 80.0%. Calculated slopes for the period from peak production to 60 wk of age and 40 wk postmolt were .596 and .671%/wk, and egg production levels at the end of each cycle were 71.2 and 61.7% for the first and second cycles, respectively. Egg production curves proved to be nonlinear with significantly greater slopes during the last 10 wk of each cycle compared with the earlier part of the cycle. This nonlinearity was shown to be associated with winter- and fall-hatched flocks for the first cycle of lay and with second cycle flocks that reached Week 30 in the spring and fall months. Calculated slopes averaged .565%/wk from peak to 50 wk of age compared with .655%/wk from 50 to 60 wk of age. Second cycle flocks had slopes of .590%/wk from peak to 30 wk postmolt compared with .819%/wk from 30 to 40 wk postmolt. Individual White Leghorn strains varied significantly in all measured traits with the exception of the calculated slope from peak egg production to Week 50 in the first cycle and from peak egg production to Week 30 in the second cycle.

Nurse-midwifery practice in the United States, 1982 and 1987.

Surveys of certified nurse-midwives living in the United States were conducted on behalf of the American College of Nurse-Midwives for 1982 and 1987. Most of the respondents were providing prenatal and family planning care. The 1982 respondents conducted 1.8 percent of the deliveries that took place in the United States during 1982 and 1988 respondents conducted 2.5 percent of all 1987 United States deliveries.

Targeting recruitment efforts for increased retention.

Recruitment efforts can be targeted towards Registered Nurses demonstrating specific sociometric, education, and practice variables. The authors describe the significant differences found in the comparative analysis within three sets of variables among two groups of hospital-employed Registered Nurses who reside in the suburbs of Chicago. These data can direct nursing administrators in strategic recruitment and retention marketing plans.

Fetal toxicity associated with maternal carbon monoxide poisoning.

We report six cases of acute carbon monoxide poisoning during pregnancy. All of the women survived with good outcomes, but three cases were associated with fetal mortality. Two fetuses were delivered stillborn within 36 hours of exposure. One fetus remained alive in utero for 20 weeks and was delivered nonviable at 33 weeks gestation with multiple morphologic anomalies. Three pregnancies were carried to term and resulted in normal neonates. Maternal blood carboxyhemoglobin levels did not correlate with the concurrent severity of symptoms in the woman. Maternal symptoms at the site of exposure seemed to predict the risk of associated morbidity to the fetus. A single maternal carboxyhemoglobin level cannot be used to estimate fetal carboxyhemoglobin if the exposure pattern is not known.

In vivo imaging of intracranial human glioma xenografts comparing specific with nonspecific radiolabeled monoclonal antibodies.

Current diagnostic and therapeutic modalities for malignant human gliomas are largely nonspecific. The development of monoclonal antibodies (MA's) with their high degree of specificity may allow precise tumor imaging and selective administration of therapeutic agents. However, the ability of these antibodies to specifically localize tumor tissue in vivo remains speculative. This study compares the localization and imaging properties of two MA's: a specific human glioma-associated extracellular matrix glycoprotein MA, 81C6, and a nonspecific control MA, 45.6, against a human glioma cell line, D-54 MG, intracranially inoculated into athymic rats. Forty-one animals received MA's labeled with iodine-131 (131I) or 125I and underwent imaging with a gamma camera. The images were independently evaluated and compared to tissue radioactivity levels. Radiolabeled antiglioma MA 81C6 specifically localized in intracranial xenografts. The percent of injected dose per gram of tissue for tumor was 1.707 +/- 0.405/gm for 81C6 and 0.118 +/- 0.056/gm for 45.6. All other organs had equivalent levels of specific and nonspecific MA's. For brain, these were 0.004 +/- 0.002/gm and 0.005 +/- 0.005/gm, respectively, and for the other organs, the range was from 0.053 to 0.284/gm. Statistically, 45.6 achieved levels in tumor that were significantly higher than normal brain (p less than 0.05) but significantly less than that achieved with 81C6 (p less than 0.005). With 81C6, the degree of localization was high enough to allow imaging of intracranial tumors at sizes as small as 20 mg. Intracranial tumors were imaged with 45.6 only when they achieved sizes greater than 300 mg. In this imaging study, radiolabeled 81C6, a specific antiglioma MA, proved to be significantly better for imaging small and intermediate-sized tumors than the control MA's. Large tumors were visualized by both MA's, although higher quality scans were obtained earlier and more frequently with specific MA's than with nonspecific immunoglobulin G. These data suggest that specific MA's have a role to play in both the diagnosis and treatment of primary intracranial human tumors.