Diagnostic and therapeutic challenges. Lesions of the optic nerve head

Unilateral injection of 10 mg all-trans retinoic acid (in 1 ml of castor oil) into the early pedicle anlage of a male fallow deer resulted in accelerated growth of the cranial appendage, and altered pedicle and first antler shape on the treatment side, whereas pedicle and antler growth on the control side, injected with 1 ml of vehicle solution only, was normal. It is concluded that retinoic acid is able to alter pedicle and first antler morphogenesis, presumably by affecting the positional information of the periosteal cells covering the incipient pedicle.     

Ether lipid biosynthesis: isolation and molecular characterization of human dihydroxyacetonephosphate acyltransferase

In this paper we describe isolation and molecular characterization of human dihydroxyacetonephosphate acyltransferase (DAP-AT). The enzyme was extracted from rabbit Harderian gland peroxisomes and isolated as a trimeric complex by sucrose density gradient centrifugation. From peptide sequences matching EST-clones were obtained which allowed cloning and sequencing of the cDNA from a human cDNA library. The nucleotide-derived amino acid sequence revealed a protein consisting of 680 amino acid residues of molecular mass 77187 containing a C-terminal type 1 peroxisomal targeting signal. Monospecific antibodies raised against this polypeptide efficiently immunoprecipitated DAP-AT activity from solubilized peroxisomal preparations, thus demonstrating that the cloned cDNA codes for DAP-AT.     

Association of cytomegalovirus genotype with graft rejection after liver transplantation

BACKGROUND: The envelope glycoprotein gB of human cytomegalovirus (CMV) occurs as one of four main genotypes. Some previous studies have proposed a relationship of CMV gB genotype to the frequency of symptomatic infection and to clinical outcomes in both transplant and human immunodeficiency virus-infected populations. Our aim was to define the distribution of CMV gB genotypes and the impact on acute cellular rejection and graft/patient survival after orthotopic liver transplantation (OLT). METHODS: Between October 1988 and December 1996, 325 patients underwent cyclosporine-based OLT at our center. CMV infection was surveyed prospectively and defined as viral isolation from blood or urine; 53 (16%) patients had detectable CMV. Isolates were genotyped by polymerase chain reaction amplification and restriction digest analysis. RESULTS: The distribution of CMV genotypes was: gB1, 19 (36%) patients; gB2, 15 (28%) patients; gB3, 13 (24%) patients; and gB4, 4 (8%) patients. Two patients (4%) had mixed infection (1 + 3, 1 + 4). Age, preOLT diagnosis, use of ganciclovir prophylaxis, basal immunosuppression, mean number of HLA donor/recipient mismatches, and United Network of Organ Sharing status were comparable among patients with different genotypes. Patients with gBl had a significantly higher mean number of acute rejection episodes (1.52+0.30 vs. 0.67+0.22; P=0.027). However, there was no difference in rejection severity, including OKT3 usage or FK506 conversion, or development of chronic rejection among patients with different genotypes. The gB genotype did not affect the development of symptomatic or tissue-invasive CMV disease, detected in 15 patients. Actuarial rates of patient (odds ratio [OR] 3.0; confidence interval [CI] 1.49-6.0) and graft (OR 2.57; CI 1.25-5.22) survival were significantly diminished in the group with CMV infection versus those without CMV (P<0.0001 for both), but there was no association with CMV genotype. CONCLUSIONS: (1) Patients with CMV infection had significantly reduced patient and graft survival rates at 1 and 5 years after OLT as compared with OLT recipients without CMV infection. (2) CMV genotype gB1 was associated with a higher mean number of acute rejection episodes.     

A phase II trial of cisplatin and 5-fluorouracil in adenocarcinoma of the oesophagus

Oxygen saturation was studied in eight newborn babies, seven preterm and one term, with and without caressing by the mother while receiving gavage feeds. The babies were stable with regard to cardiorespiratory and neurological status. Four babies were still receiving head-box oxygen. The oxygen saturation levels were similar before feeds. However, the levels were significantly higher with caressing at 10, 20 and 30 min after the feed in babies not receiving oxygen and at 20 and 30 min after feeds in babies receiving oxygen.     

Wound care: fact and fiction about hydrocolloid dressings

1. Hydrocolloid dressings have two layers. The inner, hydrocolloid adhesive layer has particles that absorb exudate to form a hydrated gel over the wound, creating a moist environment that promotes healing and protects new tissue. The outer layer (film, foam, or both) forms a seal to protect the wound from bacterial contamination, foreign debris, urine, and feces; it also maintains a moist environment and helps prevent shearing. 2. Hydrocolloid dressings are designed to be worn for up to a week. Infrequent dressing changes are less disruptive to the wound bed, provided that healthy skin is not compromised. Many patients--and even some medical professionals--still incorrectly believe that wounds need to be exposed to the air to heal properly. 3. Hydrocolloids are not always the dressing of choice in wounds that have limited drainage or in wounds with copious amounts of drainage. The hydrocolloid dressing is designed to manage drainage; if drainage is minimal, another approach may be more economical and comfortable for the patient.     

Inertia welding nickel-based superalloy: Part II. Residual stress characterization

The next generation of Ni-based alloys for aeroengines are richer in γ′ than existing alloys and are more difficult to weld by conventional means. Inertia welding is currently being developed as a joining technique for these alloys. Steep microstructural gradients have been observed in nickel-based superalloy RR1000 tube structures welded by inertia friction welding,^[1] and in this article, the concomitant residual stresses are mapped at depth using neutron diffraction. One tube in the aswelded and two in the postweld heat-treated (PWHT) condition have been investigated. In the case of the as-welded specimen, it was necessary to establish the variation of the stress-free lattice parameter, a ₀, across the weld line to infer elastic strain from lattice spacing changes. A biaxial sin² ψ measurement on thin slices was used to determine a ₀ as a function of the axial position from the weld line. This was in excellent agreement with the variation inferred by imposing a stress balance on the axial measurements. The change of a ₀ across the weld line can be rationalized in terms of the observed variation in the element partitioning effect between the matrix (γ) and the precipitates (γ′). It was found that the residual stresses in the weld and heat-affected zone generated by the welding process are large, especially close to the inner diameter of the welded ring. The experimental results have shown that, in order to relax the residual stresses sufficiently, the heat-treatment temperature must be increased by 50 °C over the conventional heat-treatment temperature. This is due to the high γ′ content of RR1000.     

Agonist-induced displacement of quinacrine from its binding site on the nicotinic acetylcholine receptor: plausible agonist membrane partitioning mechanism

It was previously demonstrated that high concentrations of cholinergic agonists such as acetylcholine (ACh), carbamylcholine (CCh), suberyldicholine (SubCh) and spin-labelled acetylcholine (SL-ACh) displaced quinacrine from its high-affinity binding site located at the lipid-protein interface of the nicotinic acetylcholine receptor (AChR) (Anas, H. R. and Johnson, D. A. (1995) Biochemistry, 34, 1589-1595). In order to account for the agonist self-inhibitory binding site which overlaps, at least partially, with the quinacrine binding site, we determined the partition coefficient (Kp) of these agonists relative to the local anaesthetic tetracaine in AChR native membranes from Torpedo californica electric organ by examining (1) the ability of tetracaine and SL-ACh to quench membrane-partitioned 1-pyrenedecanoic acid (C10-Py) monomer fluorescence, and (2) the ability of ACh, CCh and SubCh to induce an increase in the excimer/monomer ratio of C10-Py-labelled AChR membrane fluorescence. To further assess the differences in agonist accessibility to the quinacrine binding site, we calculated the agonist concentration in the lipid membrane (CM) at an external agonist concentration high enough to inhibit 50% of quinacrine binding (IC50), which in turn was obtained by agonist back titration of AChR-bound quinacrine. Initial experiments established that high agonist concentrations do not affect either transmembrane proton concentration equilibria (pH) of AChR membrane suspension or AChR-bound quinacrine fluorescence spectra. The agonist membrane partitioning experiments indicated relatively small (< or = 20) Kp values relative to tetracaine. These values follow the order: SL-ACh>SubCh>CCh-ACh. A direct correlation was observed between Kp and the apparent inhibition constant (Ki) for agonists to displace AChR-bound quinacrine. Particularly, agonist with high KpS such as SL-ACh and SubCh showed low Ki values, and this relationship was opposite for CCh and ACh. The calculated CM values indicated significant (between 7 and 54 mM) agonist accessibility to lipid membrane. By themselves, these results support the conjecture that agonist self-inhibition seems to be mediated by the quinacrine binding site via a membrane approach mechanism. The existence of an agonist self-inhibitory binding site, not located in the channel lumen would indicate an allosteric mechanism of ion channel inhibition; however, we can not discard that the process of agonist self-inhibition can also be mediated by a steric blockage of the ion channel.