Selective Embolisation of a Heavily Bleeding Cervical Fibroid in a Pregnant Woman.

We report a case of a 20-week pregnant woman, who underwent embolisation of a cervical fibroid to end a life-threatening massive bleeding. This is the first reported case in the literature of a super-selective uterine fibroid embolisation (UFE) in a pregnant woman, even though pregnancy is considered an absolute contraindication for UFE. This rare case demonstrates that UFE can be safely performed during pregnancy providing an excellent short- and long-term clinical outcome for both mother and child.

A case study of cost-efficient staffing under annualized hours.

We propose a mathematical programming formulation that incorporates annualized hours and shows to be very flexible with regard to modeling various contract types. The objective of our model is to minimize salary cost, thereby covering workforce demand, and using annualized hours. Our model is able to address various business questions regarding tactical workforce planning problems, e.g., with regard to annualized hours, subcontracting, and vacation planning. In a case study for a Dutch hospital two of these business questions are addressed, and we demonstrate that applying annualized hours potentially saves up to 5.2% in personnel wages annually.

First aid and basic life support of junior doctors: A prospective study in Nijmegen, the Netherlands.

According to the Dutch medical education guidelines junior doctors are expected to be able to perform first aid and basic life support. A prospective study was undertaken to assess the level of first aid and basic life support (BLS) competence of junior doctors at the Radboud University Nijmegen Medical Centre (RUNMC), the Netherlands. Fifty-four junior doctors (18%), of the medical students in their final years, were submitted to a theoretical test, composed of multiple-choice questions concerning first aid and basic life support. This test was followed by a practical test consisting of two out-of-hospital first aid and basic life support scenarios including cardiopulmonary resuscitation (CPR). In total, 19% of the junior doctors passed the theoretical test. The first scenario was performed correctly in 11%. The CPR situation was correctly performed by 30% of the students as observed by the examiners but when assessed by the checklists of Berden only 6% of the students performed correct CPR. It is concluded that the level of first aid and basic life support of the junior doctors at the RUNMC is low and does not meet the required level as stated in the guidelines for practice of medical education in the Netherlands.

Empirical Bayes estimation for combinations of multivariate bioassays.

This article presents a new empirical Bayes estimator (EBE) and a shrinkage estimator for determining the relative potency from several multivariate bioassays by incorporating prior information on the model parameters based on Jeffreys' rules. The EBE can account for any extra variability among the bioassays, and if this extra variability is 0, then the EBE reduces to the maximum likelihood estimator for combinations of multivariate bioassays. The shrinkage estimator turns out to be a compromise of the prior information and the estimator from each multivariate bioassay, with the weights depending on the prior variance.

A reduced-rank multivariate regression approach to aquatic joint toxicity experiments.

Classical multivariate regression techniques can lead to an asymptotically efficient restricted estimator of the regression matrix if there is evidence that the regression matrix is of reduced rank. A sublethal joint toxicity experiment involving two agents is used to illustrate this approach.

General estimation of relative potency using prior information.

A general point and interval estimator of the log relative potency is exhibited in closed form, which incorporates prior information on the log relative potency for symmetrical as well as asymmetrical parallel line bioassay. The point estimator turns out to be a weighted average of the usual estimator and the prior mean where the weights are determined by the prior variance.

Estimating relative potency using prior information.

This paper exhibits a closed-form point and interval estimator of the log relative potency that incorporates prior information on the log relative potency in a symmetric parallel line bioassay. The point estimator turns out to be a weighted average of the usual estimator and the prior mean where the weights are determined by the prior variance.

Benzidine activation in the Ames test: roles of hepatic N-acetyltransferase and other cytosolic and microsomal factors.

Benzidine (BZ) is a known animal and human carcinogen, and is mutagenic in the Ames test using strain TA 98. Several workers have shown that hepatic S9 fraction from hamster is much more effective than is rat S9, as an activation system for BZ in the Ames test. We show that rat microsomal fraction inhibits hamster S9 activation of BZ. Hamster microsomal fraction, supplemented with glucose-6-phosphate dehydrogenase (G6PdeH), gives a BZ dose-dependent mutagenic response, in the absence of cytosolic fraction. Rat microsomal fraction, in contrast, gives relatively little activation, under comparable conditions. Activation was enhanced when hamster or rat cytosol was added back to a mixture of hamster microsomes and G6PdeH. When strain TA 98 was replaced by strain TA 98/1,8-DNP6, very little activation of BZ was observed. Partially purified mouse liver acetyltransferase effectively activated BZ to mutagenic products in the presence of acetyl coenzyme A (CoASAc)/hamster microsomes/G6PdeH. Hamster and rat liver cytosol contain a CoASAc-dependent as well as a CoASAc-independent cytosolic activating factor of BZ. Hamster but not rat microsomal activation of BZ is enhanced in the presence of CoASAc. The biochemical mechanisms of BZ activation in the Ames test are discussed in light of these results.

Rat hepatic (Na+, K+)-ATPase: alpha-subunit isolation by immunoaffinity chromatography and structural analysis by peptide mapping.

The catalytic alpha-subunit of rat hepatic (Na+, K+)-ATPase (EC 3.6.1.3) has been isolated by immunoaffinity chromatography from microsomes solubilized in n-dodecyl octaethylene glycol monoether. The procedure employs an anticatalytic mouse monoclonal antibody ("9-A5") covalently linked to Sepharose 4B that specifically blocks phosphorylation of the sodium pump's alpha-subunit from [gamma-32P]ATP [Schenk, D. B., Hubert, J.J., & Leffert, H.L. (1984) J. Biol. Chem. 259, 14941-14951]. The hepatic subunit is virtually identical with purified rat, dog, and human renal alpha-subunits as judged by its apparent molecular weight after polyacrylamide gel electrophoresis in sodium dodecyl sulfate (Mr 92K) and its two-dimensional tryptic and chymotryptic peptide maps on cellulose-coated thin-layer plates. In contrast, the structures of authentic renal beta-subunits from the three species differ significantly from each other as judged by their peptide maps; no detectable homologies are seen between their chymotryptic maps and those of putative hepatic "beta"-subunits (Mr 50K and 55K) eluted from 9-A5-Sepharose. Additional studies of ouabain-sensitive 86Rb+ uptake in primary cultures of adult rat hepatocytes reveal inhibition curves with single inflection points (ID50 = 0.1 mM ouabain) in the absence or presence of pump-stimulating peptides like insulin, glucagon, and epidermal growth factor. These findings indicate that rat hepatocytes express only one of two known structurally conserved forms of catalytic subunit (the renallike alpha form) and, if at all, structurally divergent forms of the sodium pump's beta-subunit. In addition, immunoaffinity chromatography with 9-A5-Sepharose facilitates the isolation of (Na+, K+)-ATPases from nonrenal tissues with low levels of sodium pumps.

Use of a monoclonal antibody to quantify (Na+,K+)-ATPase activity and sites in normal and regenerating rat liver.

Quantitative measurements of (Na+,K+)-ATPase activity and numbers of (Na+,K+)-ATPase sites in membranes from quiescent and regenerating rat liver have been made using an anticatalytic monoclonal antibody (9-A5) that binds to alpha subunits of the sodium pump (Schenk, D. B., and Leffert, H. L. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 5281-5285). To validate the measurements, kinetic properties of 9-A5 binding to plasma membrane sodium pumps, specificity and requirements of the reactions, and mechanisms by which 9-A5 inhibits (Na+,K+)-ATPase were analyzed. 125I-9-A5 binding is saturable and reversible (k1 = 1.8 X 10(6) X M-1 X S-1; k2 = 2.7 X 10(-4) X S-1). At equilibrium, 9-A5 binds to a single class of sites revealed by Scatchard plots (KD[app] = 0.64 nM, Bmax = 29.3 pmol/mg of proteins; = 238,000 sites X cell-1). This binding requires monovalent cations (sodium, potassium, or lithium); is blocked by purified (Na+,K+)-ATPase; is inhibited noncompetitively by ATP (KI[app] = 0.5 mM); and is unaffected by ouabain. 9-A5 inhibits ATP-stimulated (Na+,K+)-ATPase noncompetitively by blocking sodium-dependent phosphorylation of alpha subunits of liver or kidney membrane (Na+,K+)-ATPase. Twelve h after 67% hepatectomy, maximal 125I-9-A5 binding to plasma membranes from regenerating liver falls 30 +/- 7% compared to sham-operated controls (p less than 0.01). In contrast, (Na+,K+)-ATPase activity in regenerating liver membranes rises 58 +/- 12% compared to controls (p less than 0.03). Similar experiments with particulate fractions from regenerating liver show insignificant decreases in maximal 125I-9-A5 binding (22 +/- 12%) but large increases in (Na+,K+)-ATPase activity (325 +/- 14%) compared to controls (p less than 0.001). No differences among groups are seen in KD values for 9-A5 binding or in the activities of plasma membrane 5'-nucleotidase (EC 3.1.3.5). Thus, stimulation of the sodium pump during the late prereplicative phase of liver regeneration is not accompanied by increases in the numbers of (Na+,K+)-ATPase sites. Instead, it appears that preexisting (Na+,K+)-ATPases are activated specifically before DNA replication starts.

Possible role for a human adenovirus in the pathogenesis of celiac disease.

Celiac disease in humans is activated by the dietary ingestion of wheat, rye, triticale, barley, and possibly oats. Gliadins in wheat and similar proteins in the other grains are known to activate disease in susceptible individuals. There is a striking association between celiac disease and HLA-B8, -DR3 and/or -DR7, and -DC3. Nonetheless, less than 0.2% of individuals with those serologic HLA specificities develop celiac disease and disease is not always concordant among monozygotic twins. We propose that additional environmental factors may be important in the pathogenesis of celiac disease. To investigate that possibility, we examined a data bank of protein sequences for other proteins that might share amino acid sequence homologies with A-gliadin, an alpha-gliadin component known to activate celiac disease and whose complete primary amino acid sequence is known. These studies demonstrate that A-gliadin shares a region of amino acid sequence homology with the 54-kD E1b protein of human adenovirus type 12 (Ad12), an adenovirus usually isolated from the intestinal tract. The region spans 12 amino acid residues, includes 8 residue identities and an identical pentapeptide, and is hydrophilic in both proteins. Antibody reactive with the 54-kD Ad12 E1b protein cross-reacts with A-gliadin, a 119 amino acid cyanogen bromide peptide of A-gliadin that spans the region of homology and a synthetic heptapeptide of A-gliadin from within the region of homology. We suggest that an encounter of the immune system with antigenic determinants produced during intestinal viral infection may be important in the pathogenesis of celiac disease.

Dog and human acid beta-D-galactosidases are structurally similar.

The purification of dog liver acid beta-galactosidase is described. The dog enzyme migrated as a single major band on polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate, with a molecular weight of 60000. Antiserum raised against purified human liver acid beta-galactosidase cross-reacted with beta-galactosidase from dog liver, but not with those from cat liver or Escherichia coli. Tryptic peptide maps of the dog and human acid beta-galactosidases indicate that 21 of the 24 peptides observed were homologous; a similar result was obtained after chymotryptic peptide mapping. We conclude that dog and human acid beta-galactosidases are structurally similar, and that canine GM1 gangliosidosis (acid beta-galactosidase deficiency) is an excellent model for the same disease in man.

Comparison of liver alcohol dehydrogenases in Fischer-344 and Sprague-Dawley rats.

Livers of Sprague-Dawley rats contain 30-100% more alcohol dehydrogenase activity than livers of Fischer-344 rats. When weight-matched rats from both strains are injected with the same dose of ethanol (1.2 g/kg), Sprague-Dawley rats achieve lower blood alcohol levels than Fischer-344 rats at all the time-points tested. Purified alcohol dehydrogenases from both strains of rats exhibit identical electrophoretic mobilities in SDS-polyacrylamide Section and in isoelectric focusing slab gels, pH optima, peptide maps, Km for ethanol, and capacities to bind monospecific rabbit antibodies. Quantitative differences in alcohol dehydrogenase activity between these strains of rats are due to differences in their liver alcohol dehydrogenase levels.

A novel molecule expressing HLA-DR antigenic determinants.

Our previous studies suggested that the polymorphism of HLA-DR antigens (the human equivalent of murine I-E antigens) was a result of structural variation in the small (beta) subunit. In order to more accurately define this polymorphism we have expanded these studies to include HLA-DR antigens isolated with monoclonal cells derived from genotypically HLA-homozygous DRw2, DR2w5, and DRw7 lymphoblastoid cells derived from offspring of consanguineous relationships. Our results indicate the large (alpha) subunits of DRw2 and DRw7 antigens are nearly identical, while their beta subunits show many differences. In contrast, both the alpha and beta subunits of the DRw5 antigen differ strikingly from the respective subunits of the DRw2 and DRw7 antigens. The significance of the variability of the DRw5 alpha subunit is in question at this point. One intriguing possibility is that DRw5 actually represents the human counterpart of the mouse I-A subregion antigen and that the monoclonal antibody is reacting with a determinant which is shared by the human equivalents of murine I-A and I-E antigens.

Small subunit of I-A subregion antigens determines the allospecificity recognized by a monoclonal antibody.

The murine major histocompatibility complex (MHC) codes for three groups of identifiable cell-surface proteins, the K, D molecules, the I-A subregion antigens and the I-E subregion antigens. All three groups of molecules display a high degree of serologically detectable polymorphism and consist of two noncovalently associated polypeptides. Amino acid sequence and peptide comparisons among allotypes of K, D and I-E molecules reveals that one polypeptide is relatively constant, whereas the other is highly variable. Thus, it is likely that only one of the two polypeptides, the variable component, determines the antigenic specificities recognized by alloantisera. In contrast to the K, D anad I-E molecules, both subunits of I-A molecules display substantial structural differences when comparisons among allotypes are made. Therefore, we have investigated whether one or both subunits of I-A molecules determine their alloantigenic specificities. Our results, presented here, indicate that only one of the two subunits determines a particular allospecificity recognized by a monoclonal antibody.