Biomedical subjects
Publications and source records attributed to A D Adams.
Tetrapeptide derived major histocompatability (MHC) II ligands have been developed that contain no unadulterated peptide bonds. These are the 'least peptidic' ligands for any MHC protein yet reported.
We describe five routine phacoemulsification procedures in which a longitudinal split in the injector cartridge occurred during foldable intraocular lens (IOL) implantation. In some cases, this was associated with a broken lens. All lenses (STAAR AA-4203VF) were folded, and implantation was attempted through a 3.5 mm corneal or scleral incision. Visual outcome was not adversely affected in any case. The systems for introducing foldable IOLs have not been perfected, and further refinements in materials and techniques are required.
Over a 12 month period, we used the anterior chamber maintainer (ACM) in cataract surgery in 258 patients; ages ranged from 15 to 95 years (mean 73 years). Surgery was performed using general or local anesthesia. The procedures were standard extracapsular cataract extraction (ECCE), mini-nuc ECCE, vectis extraction of the endonucleus, manual phacofragmentation, phacoemulsification, phacotrabeculectomy, repositioning the IOL, and anterior segment revision. We recorded our subjective assessment of the degree of anterior chamber (AC) maintenance and control of the position of the posterior capsule during surgery. We also kept clinical notes of the practical aspects of the procedures. The AC was well maintained in all patients throughout the surgery; posterior position of the posterior capsule was maintained during irrigation/aspiration. Five patients required the use of a viscoelastic agent at some stage. Our subjective assessment is that use of the ACM increased surgical control of the anterior chamber depth and position of the posterior capsule during surgery. Provided that it is used correctly, the ACM may offer increased safety during anterior segment surgery and require less use of viscoelastic agents.
The peripherin gene, which encodes a neuronal-specific intermediate filament protein, is transcriptionally induced with a late time course when nerve growth factor stimulates PC12 cells to differentiate into neurons. We have defined a negative regulatory element (NRE) that has a functional role in repressing peripherin expression in undifferentiate and nonneuronal cells. Nerve growth factor-induced derepression of peripherin gene expression is associated with alterations in proteins binding to a GC-rich DNA sequence in the NRE as detected by the DNA electrophoretic mobility shift assay (EMSA). We have utilized DNA affinity chromatography to purify from rat liver a 33-kDa DNA-binding protein that specifically recognizes the NRE. Microsequencing reveals identity with NF1-L, a member of the CTF/NF-1 transcription factor family. This protein forms a single complex when incubated with the NRE probe using EMSA analysis. The more slowly migrating complexes characteristic of crude undifferentiated PC12 cell extract are reconstituted by mixing the purified protein with the flow-through from the DNA affinity column, thereby demonstrating that protein-protein interactions are involved in complex formation. Supershift experiments incubating anti-CTF-1 antibody with undifferentiated PC12 cell extract prior to EMSA analysis confirm that NF1-L, or a closely related family member, is the DNA-binding protein component of the multiprotein complex at the NRE.
Explore the source record for details and available documents.
An efficient chemical procedure for the immobilization of carboxylate containing conjugate groups onto controlled pore glass (CPG) is described. The derivatized supports were used in the automated synthesis of an oligodeoxynucleotide (20-mer ODN) containing a 3' phosphodiester linked hexanol, aminohexyl, acridine, or cholesterol group. The stability of the oligomer in a hepatoma cell culture was found to be prolonged two to three fold by the presence of any of the 3' tails. By contrast, an aminohexyl group appended to the 5' terminus of the ODN only marginally improved its nuclease resistance. These data support the notion that antisense ODNs are primarily degraded by 3' exonucleases. Introduction of simple 3' tails which incorporate a normal phosphodiester linkage can increase ODN stability by interfering with these enzymes.
A pentadecanucleotide was prepared from 1-alpha-arabinofuranosylthymine. This novel oligonucleotide was found to hybridize to oligodeoxyadenylate, although not a s strongly as pentadecathymidylate. It formed duplex hybrids with both DNA and RNA complements, and triplex structures with a duplex containing a (dT)15-(dA)15 tract within a more complex strand. The Tm of the duplex with polyadenylate was almost the same as that of (dT)15 and polyadenylate, while its Tm with (dA)15 was substantially lower than that of the natural counterpart. A selective benzoylation of the 2'-O of a 5'-blocked alpha-ara-thymine was developed to greatly simplify the preparation of suitable blocked material for use in preparation of oligonucleotides on the automated DNA synthesizer.
A prospective, randomized study was carried out to investigate the effect of 1% sodium hyaluronate on the formation and function of trabeculectomy filtration blebs. Using a standardized operation, a group of patients had sodium hyaluronate introduced below the scleral and conjunctival flaps. In a control group the operation was done without sodium hyaluronate. Analysis of anterior chamber depth, postoperative intraocular pressure and the size and appearance of the bleb was carried out. The results showed that the use of sodium hyaluronate gives a significantly deeper postoperative anterior chamber but also suggested that it results in a filtration bleb which tends to be thinner walled and loculated.
A new procedure for the preparation of the antiviral and antitumor agent 3-deazaguanine (1) and its metabolite 3-deazaguanosine (2) has been developed by reacting methyl 5(4)-(cyanomethyl) imidazole-4(5)-carboxylate (4) and 5-(cyanomethyl)-1- (2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)imidazole-4-carboxylate (6), respectively, with hydrazine. The 3-deazaguanosine 3',5'-cyclic phosphate (13) was prepared from 5-(cyanomethyl)-1-beta-D-ribofuranosyl-imidazole-4-carboxamide 5'-phosphate. Glycosylation of the trimethylsilyl 4 with 1-O-methyl-2-deoxy-3,5-di-O-p-toluoyl-D-ribofuranose in the presence of trimethylsilyl trifluoromethanesulfonate gave the corresponding N-1 and N-3 glycosyl derivatives with alpha-configuration (18 and 20) as the major products, along with minor amounts of the beta-anomers (19 and 21). However, glycosylation of the sodium salt of 4 with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofurano se (17) gave exclusively the beta-anomers (19 and 21) in good yield. Base-catalyzed ring closure of these imidazole nucleosides gave 2'-deoxy-3-deazaguanosine (29), the alpha-anomer 28, and the corresponding N-3 positional isomers 27 and 26. The site of glycosylation and the anomeric configuration of these nucleosides have been assigned on the basis of 1' NMR and UV spectral characteristics and by single-crystal X-ray analysis for 27-29. In a preliminary screening, several of these compounds have demonstrated significant broad-spectrum antiviral activity against certain DNA and RNA viruses in vitro, as well as moderate activity against L1210 and P388 leukemia in cell culture.
Following our recent discovery that 9-beta-D-ribofuranosylpurine-6-carboxamide (1) exhibits potent antiviral activity, we were prompted to synthesize certain pyrrolopyrimidine and pyrazolopyrimidine nucleosides containing a carbamoyl function (7a,b and 13). The key precursor, 7-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine-4- carbonitrile (8a), required for the synthesis of 7a was prepared from the corresponding 4-chloro analogue (4a). Reaction of 4a with methanethiol, followed by oxidation, gave the 4-methylsulfonyl derivative (6a), which with NaCN in DMF gave 8a. Alkaline hydrolysis of 8a provided 7a. Similarly, 7b was prepared from 4-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo[3,4-d] pyrimidine (4b) via the carbonitrile intermediate 8b. Starting with thioformycin B or 7-chloro-3-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine (10) and following the similar sequence of reactions, we obtained compound 13. The in vitro antiviral studies of these carbamoyl and certain related nucleosides indicated 7a to be a potent antiviral agent against vaccinia virus, whereas 13 was moderately active. 4-Chloro-7-beta-D-ribofuranosylpyrrolo[2,3-d]pyrimidine was found to be one of the most active compounds against RVF, PICH, YF, and SF viruses in culture.
Normal human conjuctival mucus was examined by permeable membrane filter (Millipore) surface biopsy and instillation of India ink. It exists in solution in the tear film, as clusters of granules, as granular sheets, and as strands, the latter often arranged as a network. This mucus network entraps exfoliated epithelial cells, miscellaneous surface debris, carbon particles (from the India ink) and bacteria, and stains positively for lipid. Blinking causes both collapse of this mucus network into a single strand and movement of this strand to the medial canthus, where it compacts and is pushed onto the skin surface. There it dries and either falls off or is removed by rubbing. It is suggested that the formation and collapse of this mucus network represents a system for removing exfoliated surface cells and debris, infection and foreign particles, and lipid-contaminated mucus from the surface of the normal eye.
A 60-year-old man had variable visual acuity especially in the right eye for 2 years. The right field of vision showed a hemianopic defect on the nasal side (in addition to reduced visual acuity which was due to nuclear cataract). A localized posterior cortical cataract on the temporal side of the right lens accounted for the nasal field defect since the defect disappeared almost completely on dilatation of the pupil, and completely after cataract extraction. Asymmetrical opacities in the optical media far enough anterior or posterior to the plane of the pupil will produce asymmetrical field defects. (An opacity close to the plane of the pupil will produce concentric constriction.)
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Internal splinting with silicone tubing is now a well-established principle of lacrimal canaliculus repair, but fixation of the tubing ends is often unsatisfactory. The use of an internal suture allows this tubing to be converted into a small, continuous loop that is inconspicuous, cannot be inadvertently pulled out, and can remain in position indefinitely.
Explore the source record for details and available documents.
Explore the source record for details and available documents.