In early-stage vulvar cancer patients with a negative sentinel node, the groin recurrence rate is low, survival is excellent, and treatment-related morbidity is minimal. We suggest that sentinel node dissection, performed by a quality-controlled multidisciplinary team, should be part of the standard treatment in selected patients with early-stage vulvar cancer.

progress made in late-transition metal boryl complexes, a field which has seen a number of exciting developments in the past couple of years. Reviews covering other forms of metal-boron covalent and dative interactions have since appeared in a number of publications. [20][21][22][23][24][25][26][27][28][29][30][31][32] We have attempted to comprehensively cover the remaining sections regarding complexes with two-center M f B dative interactions ("borane"), B-R fragments as terminal or bridging ligands ('borylene'), and a lone boron atom as ligand ("boride").

Monomeric oxoboranes have hitherto been detected only as short-lived species in gas-phase or low-temperature matrix experiments. Here, we report formation of the oxoboryl complex trans-[(Cy3P)2BrPt(B[triple bond]O)] (Cy being cyclohexyl) by means of reversible liberation of trimethylsilylbromide from the boron-bromine oxidative addition product of dibromo(trimethylsiloxy)borane and [Pt(PCy3)2] in room-temperature toluene solution. The platinum complex is inert toward oligomerization, even under photolytic conditions and at elevated temperatures. The bromide was substituted by thiophenolate, and spectral parameters of both products as well as results of computational and x-ray diffraction studies are in agreement with the formulation of a triple bond between boron and oxygen. The boron-oxygen distance of 120.5(7) picometers shows a bond shortening of 7.2% as compared with a double bond, which is similar to the shortening observed in carbon-carbon analogs.

In theSaimiri sciureusmonkey, erythrocytes infected with the varO antigenic variant of thePlasmodium falciparumPalo Alto 89F5 clone bind uninfected red blood cells (rosetting), form autoagglutinates, and have a high multiplication rate, three phenotypic characteristics that are associated with severe malaria in human patients. We report here that varO parasites express avargene having the characteristics of group Avargenes, and we show that the varO Duffy binding-like 1α1(DBL1α1) domain is implicated in the rosetting of bothS. sciureusand human erythrocytes. The soluble varO N-terminal sequence (NTS)-DBL1α1recombinant domain, produced in a baculovirus-insect cell system, induced high titers of antibodies that reacted with varO-infected red blood cells and disrupted varO rosettes. varO parasites were culture adapted in vitro using human erythrocytes. They formed rosettes and autoagglutinates, and they had the same surface serotype and expressed the samevarOgene as the monkey-propagated parasites. To develop an in vitro model with highly homogeneous varO parasites, rosette purification was combined with positive selection by panning with a varO NTS-DBL1α1-specific mouse monoclonal antibody. The single-variant, clonal parasites were used to analyze seroprevalence for varO at the village level in a setting where malaria is holoendemic (Dielmo, Senegal). We found 93.6% (95% confidence interval, 89.7 to 96.4%) seroprevalence for varO surface-reacting antibodies and 86.7% (95% confidence interval, 82.8 to 91.6%) seroprevalence for the recombinant NTS-DBL1α1domain, and virtually all permanent residents had seroconverted by the age of 5 years. These data imply that the varO model is a relevant in vivo and in vitro model for rosetting and autoagglutination that can be used for rational development of vaccine candidates and therapeutic strategies aimed at preventing malaria pathology.

No abstract

The four distinct dihydroxyacetone phosphate dependent aldolases". ' I enjoy increasing interest for preparative asymmetric synthesis because of their capacity to build up two new stereogenic centers with high chiral induction.[31 While all DHAP aldolases have a very broad substrate tolerance for the aldol acceptor substrate, they appear to have a high substrate specificity for dihydroxyacetone phosphate (DHAP) as the aldo1 donor, and only few isosteric replacements of the phosphate ester moiety are t~l e r a t e d .~~] Diastereoselectivity may be limited for certain cases in the control of the stereocenter at C-4, which points to occasional inverse binding of the aldehyde carbonyl group.r2ck Certainly, a detailed understanding of the contributions of active site residues in substrate recognition and in the catalytic event is highly desirable to further improve the predictive value of the method.Aldolases have been divided into two classes according t o their mode of donor activation.[51 Class I aldolases achieve stereospecific deprotonation of the substrate by means of covalent linkage to an active site lysine residue (imine/enamine formation), while class I1 aldolases utilize transition metal ions (usually Zn2 +) as essential Lewis acid cofactors to facilitate deprotonation (Fig. 1). For the class I FruA,"] despite extensive efforts using modern techniques of enzymology, site-directed mutagenesis. and protein crystallography,[61 a conclusive model that accounts for the function of the active site residues in the individual steps of catalysis is advancing very slowly.[71 In particular, no structure with bound substrates or inhibitors is yet available.Based on work with the class I1 FruA from yeast, several early hypotheses for the mechanism of Zn-dependent aldolases have been developed. According to ESR and NMR relaxation rate measurements on the Mn'+-substituted holoenzyme, DHAP is bound through its phosphate group,[*] and the carbonyl is polarized by Zn2+ through an intervening imidazole ring (Fig. l , A).'91 Subsequent FT-IR and deuterium exchange studies with native yeast aldolasellO1 led to the conclusion that aldehyde activation occurs by an additional direct coordination of the carbonyl (Fig. 1, B). Recently, Dreyer and Schulz[""I reported the X-ray structure for FucA (2.13 A resolution), the first of a class I1 aldolase. The active site, which is located at the interface between two subunits of the homotetramer, contains the catalytically active Zn2+ ion tightly coordinated by three Ne atoms of histidine residues (His92, His94, His155; Fig. 1, C). Thus, all previous mechanistic hypotheses must be rejected in light of the steric restraints imposed on the Zn2+ ion. which precludes coordination of more than a single substrate, and on its histidine ligands, which cannot act as a proton relay between bound substrates. Under the slightly alkaline conditions required for FucA crystallization, the natural substrate L-fuculose 1-phosphate 1 (Scheme 1) cannot be used for X-ray analysis of the enzyme-ligand comple...

In young patients with borderline ovarian tumor a conservative treatment approach does not seem to have a significant impact on survival, and the outcome regarding fertility is good in general. It can be considered even if noninvasive peritoneal implants are discovered at the time of the initial surgery. In contrast, in patients with epithelial ovarian cancer, conservative surgery should be considered only in adequately staged patients, with a stage IA grade 1 (and probably 2) serous, mucinous or an endometrioid tumor, including a careful follow-up. Such an approach could also probably be discussed in stage IC grade 1 disease.In patients with nonepithelial malignant ovarian tumors, conservative surgery is also feasible, particularly in patients with malignant germ cell tumors because of their high chemosensitivity leading to an excellent prognosis in general.

Two bacterial aldolases, RhuA and FucA, which are readily accessible by overex‐pression, catalyze the asymmetric addition of dihydroxyacetone phosphate to various aldehydes. The high degree of enantio‐and diastereoselectivity for the L‐threo (RhuA) and D‐erythro (FucA) stereochemistry of the products and the high stability of the enzymes make it possible to prepare rare carbohydrates and their derivatives as well as other polyhydroxylated compounds.