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In a project designed to relate the unexpected in vivo and in vitro properties exhibited by (+)- and (-)-bisdehydrodoisynolic acid with their absolute stereochemical structure, an X-ray crystal-structure analysis was undertaken of the highly estrogenic, poorly binding (-) enantiomer. (1) and (13)C NMR spectra are also reported for the first time. The crystal structure shows the cis juxtaposition of the carboxyl and ethyl groups, which are separated by a large torsion angle, and that only the carbon atom holding the carboxyl group is out of the plane in which the remainder of the fused three-ring moiety lies. The crystal structure, which unequivocally characterizes the (-) enantiomer as cis-13(S),14(R) and, implicitly, the (+) enantiomer as cis-13(R),14(S), will be useful in continued studies aimed at explaining the selective estrogen receptor modulation (SERM) of these enantiomers which, in some cases, produces significantly different end-organ effects compared to those of estradiol, in both males and females, affording the promise of a variety of therapeutic and pharmacologic applications., (Copyright 2000 Wiley-Liss, Inc.)

A prototype of a new class of 2,3,1-benzodiazaborine-based estrogen mimics is described. 1,2-Dihydro-1,6-dihydroxy-2-(2-methoxy-6-pyridyl)-2,3,1-benzodiazabor ine, (6), was obtained as a crystalline monohydrate (C13H12BN3O3.H2O) after regioselective BBr3-mediated O-demethylation of the condensation product formed from 2-formyl-4-methoxybenzeneboronic acid and 2-hydrazino-6-methoxypyridine. As intended by design, the solid-state structure of (6) features an intramolecular hydrogen-bond association between the donor B--OH group and the acceptor pyridine ring N, a connection which constitutes an additional 'virtual' six-membered ring, thereby providing for an overall topography closely matching that of a tetracyclic steroid. Specifically, prototype (6) can be viewed as a boron-containing mimic of the O17-methyl ether derivatives of dihydroequilenin or estradiol.

The condensation reaction of 4-amino-6-methyl-2-pyrone with 1-cyclohexenecarboxaldehyde and a catalytic amount of (S)-(+)-10-camphorsulfonic acid in toluene at 358 K gave a 1:2.5 ratio of the title compound, (1) (C13H13NO2), and 7,8,9,10-tetrahydro-1H-pyrano[4,3-c]isoquinoline-1-one, (2). The formation of (2) presumably proceeds through an intermediate imine. Both (1) and (2) show inhibitory activities against acetylcholinesterase and human aldose reductase. Of the three linear-fused rings of (1), both ring A and ring B are planar and the angle between these planes is 0.46 (13) degrees. While the two C atoms of cyclohexane ring C attached to its common atoms with ring B are in the plane of the latter, as expected, the remaining two C atoms of ring C are out of this plane, by 0.342 (4) and -0.402 (3) A, respectively.

The structure of the fourth member of a family of structurally related 2,3,1-benzodiheteroborines has been solved by crystallographic means, providing data for proper direct comparison with the others. The title compound, 1,2-dihydro-1-hydroxy-2-methyl-2,3,1-benzodiazaborine (C8H9BN2O) is obtained via condensation of 2-formylbenzeneboronic acid and methylhydrazine, and is similar in most respects to its 2-unsubstituted parent, in internal geometry and intramolecular association topography, but has some subtle oxazaborine-like characteristics.

Using the hydrated adenosine intermediate (6R)-6-amino-1, 6-dihydro-6-hydroxy-9-(beta-D-ribofuranosyl)purine (2) produced by adenosine deaminase (ADA, EC 3.5.4.4) as a starting point, the active site probe and inhibitor platform 5-(formylamino)imidazole riboside (FAIRs, 4) was designed by removal of the-C6(OH)(NH2)-molecular fragment of 2 generated by the early events of the enzyme-catalyzed hydrolysis. FAIRs was synthesized directly from the sodium salt of 5-amino-1-(beta-D-ribofuranosyl)imidazole-4-carboxylic acid (CAIR) along a reaction sequence involving a tandem N-formylation/decarboxylation that may have a mechanistic connection to the Escherichia coli purE-catalyzed constitutional isomerization of N5-CAIR to CAIR. The physical and spectral properties of FAIRs were elucidated, its X-ray crystal and NMR solution structures were determined, and its interaction with ADA was investigated. Crystalline FAIRs exists solely as the Z-formamide rotamer and exhibits many of the same intramolecular hydrogen bonding events known to contribute to the association of Ado to ADA. In water and various organic solvents, however, FAIRs exists as NMR-distinct, slowly interconverting Z and E rotamers. This truncated enzymatic tetrahedral intermediate analog was determined to be a competitive inhibitor of ADA with an apparent Ki binding constant of 40 microM, a value quite close to that (33 microM) of the natural substrate's K(m). The actual species selected for binding by ADA, though, is likely the minor hydroxyimino prototropic form of Z-FAIRs possessing a far lower true Ki value. As the structural features of FAIRs appear well-suited to support its use as a template for constructing active site probes of both ADA and AIR carboxylases, a variety of carbohydrate-protected versions of FAIRs suitable for facile aglycon elaborations were synthesized. The N3-alkylation, N3-borane complexation, and C4-iodination of some of these were investigated in order to assess physicochemical properties that may assist in the elucidation of mechanisms for the AIR carboxylases. The survey of these properties taken together with a reasonable mechanism for the model CAIRs-->FAIRs synthetic transformation is interpreted to support a mechanism for the purE-catalyzed N5-CAIR-->CAIR biosynthetic one that involves a carboxylative sp3-rehybridization of the imidazole C4 atom rather than one possessing a dipole-stabilized C4 sp2 carbanionic intermediate.

The aim of the study was to determine immunoreactive Substance P (iSP) and immunoreactive calcitonin gene-related peptide (iCGRP) content in the human dental pulp and whether local anesthesia has an effect on the neuropeptide content. Dental pulps were obtained from patients, who underwent surgical extraction of all 4 impacted wisdom teeth under general isoflurane gas anesthesia. There was a very high interindividual variation in tissue content, with small variation in levels found in teeth from the same patient. Pulps obtained from lower teeth without local anesthesia contained an average of 131 +/- 62 fmol/mg protein of iCGRP and 15 +/- 9 fmol/mg iSP (n = 10). With additional mandibular block anesthesia the values were 194 +/- 71 fmol/mg iCGRP (statistically significant, p = 0.0356, Mann-Whitney-rank-sum-test) and 12 +/- 3.6 fmol/mg iSP. The results suggest that local anesthesia attenuates neuropeptide release in the human dental pulp during surgical extraction.

Two cases are reported in which retained wooden foreign bodies in the facial tissues posed considerable diagnostic difficulty and were the source of persistent and distressing symptoms. In both patients the embedded foreign material defied radiological identification and in case 1 the time between injury and final removal of the foreign body was 9 years. The cases are described to highlight the problems in managing penetrating injuries when there is the possibility that radiolucent material is implanted in the wound.

Condensation of 2-formylbenzeneboronic acid and 1,1-dimethylhydrazine afforded the title compound, bis(8-B-4)-1,3,5-tris[2-[(N,N-dimethylhydrazono)methyl]-phenyl)]b oroxin, C27H33B3N6O3, a tridehydro cyclic trimer of the expected simple benzaldehyde hydrazone and the first triphenylboroxin derivative found to possess two B chelating interactions. The double chelation induces molecular asymmetry but effects only a slight puckering in the central boroxin ring.

A gene responsible for X-linked mental retardation with macrocephaly and seizures (MRX38) in a family with five affected males in three generations was localized to Xp21.1-p22.13 by linkage analysis. Recombination events placed the gene between DXS1226 distally and DXS1238 proximally, defining an interval of approximately 14 cM. A peak lod score of 2.71 was found with several loci in Xp21.1 (DXS992, DXS1236, DXS997, and DXS1036) at a recombination fraction of zero. The map intervals of 5 X-linked mental retardation loci, MRX2 (Xp22.1-p22.2), MRX19 (Xp22), MRX21 (Xp21.1-p22.3), MRX29 (Xp21.2-p22.1), and MRX32 (Xp21.2-p22.1), and two syndromal mental retardation loci, Partington syndrome (PRTS; Xp22) and Coffin-Lowry syndrome (CLS; Xp22.13-p22.2), overlap this region. As none of these display the same phenotype seen in the family reported here, this X-linked mental retardation locus may represent a new entity.

The purpose of this study was to provide a profile of the competition strategy used by the world's top squash players at the international level and provide recommendations for other players to improve their playing strategy. A total of 10 matches including three in round one, the four quarter finals, the two semi-finals, and the final of the 1993 Hong Kong Squash Open were filmed using a 3-CDD video camera. The tournament was played under the North American scoring system. Notational analysis which is based on frame by frame video analysis was used to categorize a player's motion. The frequency of each stroke, and the success or failure rate of each stroke were recorded. Shots were classified as "effective", "ineffective", "winning" and "losing" shots and the analysis demonstrated that 70.28% were "effective", 19.86% were "ineffective", 5.37% were "winning" and 4.48% were "losing" shots. The mean number of shots per game was 252.09. The order of priority using different kinds of strokes in matches were as follows: drive (length) (60.79%), drop (17.91%), volley (11.79%), boast (4.80%), and lob (4.72%). The results of this study show that the "pressure and attack game" was the most important strategy for the world's top squash players in producing winning performances. Also identified are the strokes and the strategies which should be practiced to improve performance. This method of notational analysis can be utilized to evaluate the strengths and weaknesses of players at all levels of competition.

The timing of temporomandibular joint (TMJ) development in the cotton-eared marmoset was studied by histological examination of joints taken during embryogenesis and compared with TMJ development reported in man. Specimens were obtained via hysterotomy at intervals during pregnancies dated by estimation of uterine size or fetal head diameter. Elements of the marmoset TMJ were first identified at 70-85 days gestation, and TMJ morphogenesis was complete at 110-125 days. The chronological events of TMJ embryogenesis were found to run parallel to the human but were delayed by 30 days. At birth, after 150 days gestation, the marmoset TMJ resembled the human joint at the end of the second trimester, with all cell layers of the condylar cartilage in place and ossification started in temporal and condylar components. A new world primate, the cotton-eared marmoset is proposed as an animal model for craniofacial studies involving the TMJ on grounds of its close comparability to man.

The management of impacted third molars, particularly the indications for their removal, is judged against a constantly changing climate of professional opinion, public attitudes to treatment and the funding of healthcare. These changes highlight the practitioner's dilemma: to remove an impacted wisdom tooth or to leave well alone? This article discusses the indications for and risks of wisdom tooth removal, and suggests guidelines for dealing with the dilemma.

The title compound, C16H21NO2S, isolated from the reaction of lithiated racemic 2,3,4,4a,5,6,7,8-octahydroquinoline with 0.5 equivalents of (-)-(1R,2S,5R)-menthyl (SS)-p-toluenesulfinate, possesses the unusual conformation in which the OH and bulky p-toluenesulfinyl groups are in axial positions. The S=O bond distance of 1.519 (3) A is longer than expected because of intramolecular hydrogen bonding between the hydroxyl group and the sulfinyl O atom.

This study tests the regenerative capability of condylar cartilage by examining repair of full-thickness articular surface defects in a primate model. The wounds were reconstituted within 6 months with tissue identical to the remaining condylar structure, and the reformed articular surface was maintained intact up to 1 year postinjury.

Clinical evidence and previous experimental animal work suggest that mandibular condylar cartilage shows the capacity for repair, after trauma or degeneration, that can reconstitute a functional articular surface; a facility not shared by other synovial joints. This study aims to test the regenerative capability of condylar cartilage in the repair of standardised full-thickness articular defects, and thereby to test the hypothesis that the healed wounds comprise tissues identical in form and composition to those of similar, but uninjured areas. Articular defects were produced at open arthrotomy of the temporomandibular joints in the young adult cotton eared marmoset. After healing periods of between 3 days and 1 year, repairing wounds were examined using histological, autoradiographic and immunocytochemical methods in an attempt to identify tissue architecture, cell proliferation and cartilage matrix components. The results showed reconstitution of all tissue elements of condylar cartilage within 6 months of injury. Glycosaminoglycans reformed at an early stage and appeared to be associated with type I collagen fibrillogenesis. Subsequently, type II collagen and aggregated proteoglycans accumulated from 8 weeks postoperatively, coinciding with organisation of the cell layers of condylar cartilage. The reformed tissue was maintained intact for the period studied (up to 1 year).

The title compound, derived in four steps beginning with the cyclopropanation reaction of the anion of the alpha-sulfinyl ketimine (4R,SS)-4-(tert-butyldimethylsilyloxy)-3,4-dihydro-5-(p-tolysul finyl)methyl)-2H-pyrrole with 2-chloroethyl trifluoromethanesulfonate, contains a shorter than expected bond (C(7)--C(8) 1.48(l) A) and a larger than expected angle (S(1)--C(6)--C(2) 123.2(6) in the cyclopropane framework.

C18H19O3P, M(r) = 314.32, monoclinic, P2(1)/n, a = 5.726 (6), b = 14.234 (7), c = 20.08 (1) A, beta = 92.54 (7) degrees, V = 1635 (4) A3, Z = 4, Dx = 1.277 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 1.71 cm-1, F(000) = 664, T = 296 K, R = 0.042, 1813 unique observed reflections. The X-ray structure determination of the title compound shows that the dioxaphosphorinane ring has a chair conformation in which the phosphoryl O atom (P=O) is equatorial, which explains the absence of substantial NMR deshielding by its P=O group on H(4) and H(6), which are axial.

1-(9-Hydroxyfluoren-9-yl)-2,2-dimethyl-1-propanone, C18H18O2, M(r) = 266.34, orthorhombic, Pbcn, a = 18.917 (10), b = 11.843 (8), c = 13.177 (7) A, V = 2952 (5) A3, Z = 8, Dx = 1.198 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.72 cm-1, F(000) = 1136, T = 296 K, R = 0.044 for 1042 unique observed reflections. Conversion of ap-9-pivaloylfluorene, ap-(I), into lithiated (I)-9-anion followed by the addition of MeOH, then H2O, led to unexpected hydroxylation to provide 20-40% of sp-9-hydroxy-9-pivaloyfluorene, sp-(II), and 60-80% recovery of ap-(I). The singular sp conformation of (II) in solution suggested by NMR was confirmed in the crystalline state by X-ray diffraction which showed the O(1)-C(9)-C(10)-O(2) torsion angle approximately 0 degrees and the C(10) = O(2)...H(9)-O(1) non-bonding distance 1.95 (4) A, suggesting strong intramolecular hydrogen bonding in this conformation.

The title compound contains the tetracyclic A-B-C-E ring system of cephalotaxus alkaloids. Unexpectedly, the five-membered-ring plane is twisted 67.2 degrees from the aromatic ring plane and, like cephalotaxine, the seven-membered ring is oriented in a boat form with the nitrogen at the prow.

C15H15NOS, Mr = 257.35, monoclinic, P2(1), a = 7.710 (2), b = 5.903 (5), c = 14.700 (3) A, beta = 91.48 (2) degrees, V = 668.8 (6) A3, Z = 2, Dx = 1.278 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 2.18 cm-1, F(000) = 272, T = 296 K, R = 0.043, 944 unique observed reflections. This is the first structure determination of an N-alkylidenesulfinamide. The C = N bond is distorted and lengthened presumably because of the steric interaction and electron-withdrawing effect of the sulfinyl group. The nonplanar conformation is also a result of repulsive steric interaction. The configuration at C = N is trans. The title compound was obtained from the displacement reaction of (-)-1-methyl (S)-p-toluenesulfinate with methyllithium.

Bone scintiscans comparing the uptake of technetium 99 in the normal and affected condyles of 10 patients with unilateral condylar hyperplasia were recorded at or after the time when overall growth had ceased. The scans of 6 patients demonstrated persisting increased growth activity at this time. In 2 of these cases where the abnormal condyles showed uptakes of 240% and 170% with respect to the normal side, the nature and timing of treatment were changed when the results of the scans were known.

C16H19NO2S, Mr = 289.39, orthorhombic, P2(1)2(1)2(1), a = 11.467 (5), b = 17.207 (8), c = 7.566 (4) A, V = 1493 (2) A3, Z = 4, Dx = 1.29 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 2.07 cm-1, F(000) = 616, T = 296 K, R = 0.049, 928 unique observed reflections. The structure determination combined with the known S configuration at the sulfur site discloses the stereochemistry of the title compound to be 7S and SS.

Health care professionals are recognizing the need to treat their patients not only as individuals, but as part of a social network--the family. In order for health care organizations to provide a total family care program and, therefore, a more efficient and effective health care delivery system, they must develop and implement strategies to identify and treat all of the patient's needs--psychological, biological, and familial. Coordination among individual departments and personnel is critical to ensuring that resources meet these needs. The trend toward total patient and family services will continue to be emphasized and refined by the leaders in the health care industry.

A case of aneurysmal bone cyst in the maxilla is reported which developed following the excision of a cementifying fibroma from the same site. Aneurysmal bone cyst has been seen previously in association with other osseous lesions in the jaws and in other bones. A review of the literature revealed 58 cases of aneurysmal bone cyst in the jaws, of which 13 were associated with other bone disease. One theory of pathogenesis of aneurysmal bone cyst is supported by the finding of such hybrid lesions.