Advances in the surgical techniques, preservation solutions, and methods for predicting eventual long-term renal function from expanded donors will be critical in allowing precise selection criteria for kidneys for transplantation, resulting in the optimum use of a scarce and precious resource. Until other options such as xenotransplantation or tissue engineering become realistic, the challenge for the millennium will be to identify which donor organs previously considered suboptimal can be safely used to expand the organ donor pool.

Adolescent↗

PubMedDate not supplied

Synthesis and conformation of a dinucleoside monophosphate modified by aniline.

The modified dinucleoside monophosphate, N-[deoxycytidylyl-(3'-5')-guanosin-8-yl]aniline (dCprG-An) has been prepared by the phosphotriester synthesis approach, using suitably blocked derivatives of dCp and N-guanosin-8-ylaniline (rG-An). The latter compound was synthesized by a route that featured nucleophilic displacement by antiline upon an 8-bromoguanosine derivative. A number of attempts to prepare N-(deoxyguanosin-8-yl)aniline (dG-An) by electrophilic substitution, using activated aniline derivatives, failed. Nucleophilic substitution reactions of aniline with 8-bromodeoxyguanosine derivatives afforded only the base, N-guanin-8-ylaniline. The conformation of dCprG-An has been studied by CD, proton magnetic resonance, and minimized potential energy calculations. A flexible molecule with a mixture of conformers is indicated. Base-base stacked states predominate, in contrast to the case of a dimer containing 4-aminobiphenyl bound to the 8-position of guanine, where carcinogen-base stacked states are dominant. The mutagenic and carcinogenic activities of aniline are much less than those of many polycyclic aromatic amines. The diminished stacking ability of the aniline ring, as well as the weak electrophilic reactivity of activated aniline derivatives, may be a cause of this weak biological activity.

Dinucleoside Phosphates↗

PubMedDate not supplied

Conformation of amine-modified DNA: 2-aminofluorene- and 2-(acetylamino)fluorene-modified deoxydinucleoside monophosphates with all possible nearest neighbors. A comparison of search and optimization methods.

Although a significant part of the replication fork exists as single-stranded DNA, little is known about the effect of carcinogens and mutagens on single-strand conformation. Large-scale conformational searches with potential energy minimization, using the torsion angle space molecular mechanics program DUPLEX, were employed to explore the conformation of all 16 deoxydinucleoside monophosphates bearing 2-aminofluorene (AF) or 2-(acetylamino)fluorene (AAF) modification on guanine. We have thus examined the effect of 3' versus 5' modification, the presence or absence of the acetyl group, and the effect of four different neighbors in each case. The principal effect of the acetyl group appeared to be the destabilization of anti (and, to a lesser degree, borderline anti) conformations for modified guanine. This mattered little in the 5'-substituted dimers, where one conformational type predominated in the low-energy structures for the adducts of both AAF and AF: It was right-handed, with syn-guanine, imperfect base-base stacking, and fluorene to 3'-sugar contacts. Greater divergence was seen in the 3'-substituted series. The AAF-substituted 3'-adducts primarily displayed good base-fluorene stacking, with syn-guanine in contact with the 5'-sugar. The AF-substituted 3'-adducts displayed a variety of structures which included base-base and carcinogen-base stacked forms. Two novel forms were encountered [global minima for d(ApG-AF) and d(GpG-AF)], whose unusual structures suggest mutagenic capability. In order to address the multiple minimum problem, we conducted our searches of conformation space using two alternative optimization methods that also employ differing search strategies. We used the Powell algorithm, BOTM, with starting conformations that are selected combinations of rotamers, and the method of simulated annealing (SA), with random or arbitrary starting conformations. While both approaches were effective in defining the most important structures, SA was more successful than BOTM in locating the structures of lowest energy.

2-Acetylaminofluorene↗

PubMedDate not supplied

Major and minor groove conformations of DNA trimers modified on guanine or adenine by 4-aminobiphenyl: adenine adducts favor the minor groove.

We have studied the conformational effects of 4-aminobiphenyl modification at C-8 of guanine or adenine on double-stranded DNA trimers. We used sequences with the modified purine at the central base pair and all 16 possible neighboring sequences at the outer pairs. Minimized potential energy calculations were carried out using the molecular mechanics program DUPLEX to survey the conformation space of these adducts, using a total of 1280 starting structures both in the modified guanine series and in the modified adenine series. Conformer families in which the bound 4-aminobiphenyl was located in the DNA major groove, and in the minor groove, were located for both adenine and guanine modification. In the modified guanine series, the major and minor groove families were roughly comparable in energy, and the sequence context determined which was more stable in a particular case. In the modified adenine series, however, the minor groove structure was more than 10 kcal/mol more stable than the major groove structure for all sequences. As a result, minor groove adducts provided most of the global minima in the adenine-modified series. This result may be relevant to a previous mutagenesis study [Lasko et al. (1988) J. Biol. Chem. 263, 15429-15435] in which the hot spot of most frequent occurrence was located at an adenine, in the sequence GAT.

Adenine↗

PubMedDate not supplied

Mechanism of obstruction of the infradiaphragmatic portion of the inferior vena cava in the presence of increased intra-abdominal pressure.

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Abdomen↗

PubMedDate not supplied

A consideration of the systemic factors that influence frontal sinus pneumatization.

The authors present the embryology and comparative anatomy of the frontal sinuses pertinent to a discussion of the systemic factors which influence frontal sinus pneumatization. There are at least three important factors involved: 1) craniofacial configuration, 2) thickness of the frontal bone, 3) growth hormones. Various clinical entities which illustrate these points are discussed.

Animals↗

PubMedDate not supplied

Adjunctive hyperbaric oxygen in the treatment of thermal burns. An economic analysis.

Current reimbursement for burn care underscores the importance of cost containment in the treatment of burn injuries. We evaluate the economic impact of adjunctive hyperbaric oxygen in burns of 19% to 50% total body surface area in patients admitted to our burn center from January 1982 to July 1987. Length of hospitalization, number of surgical procedures, and total cost of care, exclusive of surgical fees, were examined. Eleven patients did not receive adjunctive hyperbaric oxygen therapy, whereas 10 did. The hyperbaric oxygen-treated group had an average decrease in length of stay of 14.8 days, a reduction of surgical procedures of 39%, and an average saving per case of $31,600.

Adolescent↗

PubMedDate not supplied

Computed tomography in the study of the development of the skull base: 1. Normal morphology.

We examined 11 human fetuses (18 to 30 weeks' gestation) with high resolution CT to study the developmental ossification of the two main component structures of the skull base, the temporal and sphenoid bones. Computed tomography, with its excellent contrast discrimination, allowed clear visualization of the morphology of ossifying centers. Skull base growth during this gestational period was found to be a dynamic event with rapid changes in morphology and interosseous relationships. The growth of the sphenoid body on CT corroborates the studies done by Kodama, who used dehydrated skulls. The temporal bone proceeded in a stepwise fashion; complete encapsulation of the membranous labyrinth occurred before it grew anteroposteriorly to form the apex and mastoid.

Gestational Age↗

PubMedDate not supplied

Venous aneurysms: MR diagnosis with the "layered gadolinium" sign.

OBJECTIVE: Our goal was to present MR findings in venous aneurysms and introduce the "layered gadolinium" sign as an ancillary diagnostic finding. METHOD: Gadolinium-enhanced MR images of three patients with retroperitoneal venous aneurysms were retrospectively reviewed. Prior to MRI, venous aneurysm had been suspected clinically in only one patient. Surgical correlation was available in one patient. A phantom was constructed and imaged to investigate the cause of the layered gadolinium sign. RESULTS: A gradation of signal intensity, the layered gadolinium sign, was observed in three patients with venous aneurysms on postcontrast T1-weighted images. The anterior portion of the aneurysms demonstrated high signal intensity separated by a sharp interface from the low signal intensity posterior region. Unenhanced time-of-flight MR venography, color Doppler, and duplex sonography failed to demonstrate flow in the patient with surgical proof. CONCLUSION: The layered gadolinium sign may be helpful in the diagnosis of venous aneurysm and in differentiating these masses from solid neoplasms.

Aged↗

PubMedDate not supplied

The effect of ankle stabilizers on athletic performance. A randomized prospective study.

The ankle is the site of more than one third of all injuries that occur to male basketball players. Although ankle bracing may prevent injury, many players believe that braces restrict athletic performance. This belief discourages use of braces and obviates the injury protection that bracing provides. The objectives of this study were to 1) determine whether athletic performance (in four basketball-related activities) was affected by three ankle brace designs (Universal, Kallassy, and Air-Stirrup ankle training brace), 2) determine whether specific braces are better for specific athletic activities, and 3) determine whether athletic performance changes with brace use. Twelve high school basketball players wore each brace type while vertical jumping, standing long jumping, cone running, and 18.3-meter shuttle running at two test times (initially and after 1 week of acclimation). Our data showed that these braces had no significant effects on athletic performance. No brace affected athletic performance in one specific activity more than another, and athletic performance did not change with brace use. We concluded that prophylactic ankle bracing does not inhibit athletic performance.

Adaptation, Physiological↗

PubMedDate not supplied

Protein binding of coumarin anticoagulants in disease states.

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Blood Proteins↗

PubMedDate not supplied

Initial studies with FK506 in renal transplantation.

FK506 is a novel immunosuppressive agent which is approximately 100 times as potent as cyclosporine in vitro. In this initial trial, 65 renal transplant patients of high complexity received primary FK506 immunosuppression. Overall, graft and patient survival rates are 80% and 98.5%, respectively. A major advantage of FK506 is its potency with relatively few side effects, which has permitted elimination of steroids in 31 (60%) of these patients. Because of these encouraging results, a randomized trial comparing the therapeutic efficacy and toxicity of FK506 and cyclosporine is currently underway at our institution.

Follow-Up Studies↗