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[reaction: see text]. The allylic substitution of racemic 5-vinyloxazolidinones with phthalimide and a chiral palladium catalyst afforded optically enriched regioisomeric products. Optimal divergence was found by employing chiral DIOP ligands in toluene. These results demonstrate the influence of chiral ligand/chiral substrate matching on the regioselectivity in a novel resolution strategy.

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[formula: see text] The enantioselective formal synthesis of balanol, a potent protein kinase C inhibitor, was accomplished from D-serine utilizing a Pd-catalyzed equilibration of diastereomeric 5-vinyloxazolines to set the stereochemistry of the vicinal amino and hydroxyl groups. A ruthenium-catalyzed ring-closing metathesis was employed to form the seven-membered nitrogen heterocyle.

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A patient with an oesophageal adenocarcinoma, recent onset of digital clubbing, and evidence of increased oestrogen synthesis is presented. In the discussion, some of the theories of the pathogenesis of clubbing are reviewed, together with previous reports of clubbing in gastro-oesophageal disorders. A possible unifying theory is proposed for our case which we believe is the first report of this triple association.

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Using high performance liquid chromatography we have successfully purified four core histones from mature human sperm chromatin. The H2A variants present in sperm (H2A.X and limited H2A.Z) have been shown previously to be minor variants in somatic chromatin. The histones are highly modified as evidenced by extensive acetylation and an as yet uncharacterized multicharge modification of H2B. Based on our data, we conclude that histone proteins are a minor component of each mature spermatozoa. Given the unique nature of the histone variants present in sperm, we propose that this chromatin component has a specific function and may possibly facilitate the programming of genes which will be active in early development.

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Transcription factor IIIA (TFIIIA), the canonical zinc-finger protein, is a protein of relative molecular mass 39,000 (39K) that is required for transcription of 5S-ribosomal subunit genes in Xenopus. It binds in a sequence-specific manner to the internal control region of the 5S gene (see Fig. 1) and facilitates transcription of the gene by RNA polymerase III. It also binds to the 5S gene product to form a 7S ribonucleoprotein particle. In oocytes the 7S particle acts as a storage form of the RNA to be utilized later in development. TFIIIA binds to DNA through its 30 K N-terminal domain, which contains nine zinc-fingers. TFIIIA was the first protein described to have this type of DNA binding motif, but numerous other proteins have now been shown to have zinc-finger domains. A structure for a single zinc-finger from the yeast protein ADR1, was recently proposed based on two-dimensional NMR data (ref. 8), and a similar structure was proposed based on comparison with crystal structures of other metalloproteins. Although models for the interaction of TFIIIA with the 5S-ribosomal gene DNA have been proposed, based on nuclease digestion and methylation interference data, little precise structural information is available for TFIIIA and the physical basis for the interaction of zinc-fingers with DNA is not understood. Using both circular permutation and circularization assays we provide convincing biochemical evidence that TFIIIA bends the DNA at the internal promoter of the 5S gene.

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The binding of high mobility group (HMG) protein 17 to the nucleosome core particle has been studied in D2O solution using 1H NMR at 500 MHz. Spectra were obtained for purified HMG 17, purified nucleosome core particles, and the reconstituted HMG 17-nucleosome core particle complex at 0.1, 0.2, 0.3, and 0.4 M NaCl. Subtraction of the core particle spectra from spectra of the core particle reconstituted with HMG 17 demonstrated those regions of HMG 17 which interact with the nucleosome at different ionic strengths; the resonance peaks of interacting groups are broadened due to their restricted mobility. At 0.1 M NaCl, the mobility of all the amino acid side chains of HMG 17 was restricted, indicating complete binding of HMG 17 to the much larger nucleosome core particle. At 0.2 M NaCl most of the amino acids were free with the exception of arginine and proline which are confined to or predominant in the basic central region of HMG 17. These amino acids were completely free only at 0.4 M NaCl. We conclude that the entire HMG 17 molecule interacts with the nucleosome core particle at physiological ionic strength. The acidic COOH-terminal region of HMG 17 is released from interaction with the core histones at an NaCl concentration between 0.1 and 0.2 M and so binds weakly at physiological ionic strength. The basic central region binds more strongly to the core particle DNA, being completely released only at much higher ionic strength, between 0.3 and 0.4 M NaCl.

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The DNA in human sperm chromatin is packaged into nucleoprotamine (approximately 85%) and nucleohistone (approximately 15%). Whether these two chromatin fractions are sequence-specific subsets of the spermatozoon genome is the question addressed in this report. Sequence-specific packaging would suggest distinct structural and functional roles for the nucleohistone and nucleoprotamine in late spermatogenesis or early development or both. After removal of histones with 0.65M NaCl, exposed DNA was cleaved with Bam HI restriction endonuclease and separated by centrifugation from insoluble nucleoprotamine. The DNA sequence distribution of nucleohistone DNA in the supernatant and nucleoprotamine DNA in the pellet was compared by cloning size-selected single-copy sequences and by using the derived clones as probes of nucleohistone DNA and nucleoprotamine DNA. Two clones derived from nucleohistone DNA preferentially hybridized to nucleohistone DNA, and two clones derived from nucleoprotamine DNA preferentially hybridized to nucleoprotamine DNA, which demonstrated the existence of sequence-specific nucleohistone and nucleoprotamine components within the human spermatozoon.

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The "neighbor relationship" of lamb thymus high mobility group (HMG) protein 17 to native HeLa nucleosome core particle histones in the reconstituted complex has been studied. 125I-Labeled HMG 17 was cross-linked to core histones using the protein-protein cross-linking reagent 2-iminothiolane. Specific cross-linked products were separated on a two-dimensional Triton-acid-urea/sodium dodecyl sulfate-gel system, located by autoradiography, excised, and quantified. Disulfide bonds in the cross-links were then cleaved, and the protein constituents were identified by sodium dodecyl sulfate-gel electrophoresis. HMG 17 cross-linked primarily to histone H2A while lower levels of cross-linking occurred between HMG 17 and the other histones. In contrast, cross-linking between 2 HMG 17 molecules bound on the same nucleosome core particle was relatively rare. We have concluded that H2A comprises part of the HMG 17 binding site. Less contact occurs between HMG 17 and the other core histones, and there is little contact possible between the 2 bound HMG 17 molecules. These results are in agreement with the current model for the structure of the nucleosome and the proposed binding sites for HMG 17.

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A 32-year-old black man had a deeply pigmented anterior uveal lesion that was indenting and subluxing the lens. The mass was successfully removed by a sector iridectomy and diagnosed histologically as an adenoma of the iris pigment epithelium. Although this rare tumor is sometimes misdiagnosed clinically as a malignant melanoma or iris cyst, it has distinctive clinical features which should differentiate it from these other entities.

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We conducted a ten-year follow-up of an unusual pedigree with an autosomal recessive vitreoretinal degeneration, severe myopia, and congenital encephalocele. All five affected members (four girls and one boy) also had early, recurrent bilateral detachments. Color vision testing disclosed an acquired tritan dyschromatopsia and electroretinography showed subnormal photopic and scotopic amplitudes, delayed b-wave implicit times and 30-Hz flicker-phase relations, and absent scotopic b-wave oscillations.

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