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Biomedical subjects

R S Larson

Publications and source records attributed to R S Larson.

50 records · Page 3Linked to original sources
PubMed1989

Neodymium:YAG laser zonulysis for treatment of lens subluxation.

Nine eyes with lens subluxation in seven patients (6 patients with Marfan's syndrome, 1 with idiopathic lens subluxation) were treated by neodymium:YAG (Nd:YAG) laser zonulysis. The procedure uses an Nd:YAG laser to lyse the zonules to obtain a clear aphakic visual axis. Pretreatment best-corrected visual acuity was 20/60 or worse in eight eyes (6 eyes less than or equal to 20/200). Movement of the crystalline lens was achieved after zonulysis in all cases (100%), and a clear aphakic visual axis, sufficient to maintain aphakic correction without diplopia or glare, was obtained in eight eyes (88.9%). The procedure was combined with optical iridotomy in three cases (33.3%). Five cases (55.6%) required more than one zonulysis treatment. Visual acuity improved two or more Snellen lines in all but one eye (7 eyes greater than or equal to 20/60). Four cases had complications which included: increased intraocular pressure (IOP), mild iritis, recurrent migration of the lens into the visual axis, and crystalline lens damage. The final two complications necessitated eventual surgical removal of the lens. These results suggest that Nd:YAG laser zonulysis may be of benefit as an alternative treatment modality for selected patients with lens subluxation.

Adult↗
PubMed1989

Primary structure of the leukocyte function-associated molecule-1 alpha subunit: an integrin with an embedded domain defining a protein superfamily.

The leukocyte function-associated molecule 1 (LFA-1, CD11a/CD18) is a membrane glycoprotein which functions in cell-cell adhesion by heterophilic interaction with intercellular adhesion molecule 1 (ICAM-1). LFA-1 consists of an alpha subunit (Mr = 180,000) and a beta subunit (Mr = 95,000). We report the molecular biology and protein sequence of the alpha subunit. Overlapping cDNAs containing 5,139 nucleotides were isolated using an oligonucleotide specified by tryptic peptide sequence. The mRNA of 5.5 kb is expressed in lymphoid and myeloid cells but not in a bladder carcinoma cell line. The protein has a 1,063-amino acid extracellular domain, a 29-amino acid transmembrane region, and a 53-amino acid cytoplasmic tail. The extracellular domain contains seven repeats. Repeats V-VII are in tandem and contain putative divalent cation binding sites. LFA-1 has significant homology to the members of the integrin superfamily, having 36% identity with the Mac-1 and p150,95 alpha subunits and 28% identity with other integrin alpha subunits. An insertion of approximately 200 amino acids is present in the NH2-terminal region of LFA-1. This "inserted/interactive" or I domain is also present in the p150,95 and Mac-1 alpha subunits but is absent from other integrin alpha subunits sequenced to date. The I domain has striking homology to three repeats in human von Willebrand factor, two repeats in chicken cartilage matrix protein, and a region of complement factor B. These structural features indicate a bipartite evolution from the integrin family and from an I domain family. These features may also correspond to relevant functional domains.

Amino Acid Sequence↗
PubMed1989

Neodymium: YAG laser vitreolysis for treatment and prophylaxis of cystoid macular oedema.

Eighteen eyes with vitreous strands adherent to the corneoscleral wound of previous cataract surgery were treated with neodymium: YAG laser to achieve vitreolysis. Twelve eyes were treated for management of cystoid macular oedema (CMO group) and six eyes were treated for prophylaxis of possible CMO (prophylactic group). In the CMO group, visual acuity improved two or more Snellen lines in 10 eyes (83.3%) and seven eyes had a post-laser visual acuity of 20/40 or better (one eye had a pre-treatment visual acuity of 20/40 or better). In the prophylactic group, visual acuity was either maintained at the pre-treatment level or improved in five eyes (83.3%) eighteen months after laser treatment. This procedure was complicated by retinal detachment in one case and elevation of intraocular pressure over 10 mmHg in another case.

Adult↗
PubMed1988

Chromosomal location of the genes encoding the leukocyte adhesion receptors LFA-1, Mac-1 and p150,95. Identification of a gene cluster involved in cell adhesion.

The adhesion receptors Mac-1, LFA-1, and p150,95 are cell surface alpha/beta heterodimers that play a key role in leukocyte adhesion processes. The genes for Mac-1, LFA-1, and p150,95 alpha subunits have been located to chromosome 16 by means of Southern blot analysis using a series of somatic cell hybrids. Chromosomal in situ hybridization has demonstrated that the genes for the three alpha subunits map to the short arm of chromosome 16, between bands p11 and p13.1, defining a cluster of genes involved in leukocyte adhesion. The gene encoding the LFA-1/Mac-1/p150,95 beta subunit, and defective in leukocyte adhesion deficiency, has been located on chromosome 21, band q22. The leukocyte adhesion receptor alpha and beta subunits are mapped to chromosomal regions that have been shown to be involved in cytogenetic rearrangements in certain patients with acute myelomonocytic leukemia and the blast phase of chronic myelogenous leukemia, respectively.

Animals↗
PubMed1988

Terbutaline stimulates aqueous humor flow in humans during sleep.

A randomized, double-masked study of the effect of terbutaline sulfate, a selective beta 2-agonist, on the rate of aqueous humor formation was performed in awake and sleeping normal human subjects. The rate of aqueous formation was measured by fluorophotometry. Both the drug- and placebo-treated eyes showed a statistically significant nocturnal reduction of the flow rate (36% suppression in the terbutaline-treated eyes and 43% suppression in the placebo-treated eyes). Terbutaline had no effect on daytime aqueous flow rates, but stimulated flow by 15% during sleep. The drug had no significant effect on intraocular pressure. This study confirms past observations that beta-agonists exert their maximal effects during sleep, when endogenous adrenergic stimulation is at a minimum.

Adult↗
PubMed1988

Isoproterenol stimulates aqueous flow in humans with Horner's syndrome.

Topical 1 percent isoproterenol in the presence of the phosphodiesterase inhibitor theophylline was tested for its ability to stimulate the rate of aqueous humor flow through the anterior chamber of the normal and the partially adrenergically denervated human eye (Horner's syndrome). Both the affected eye and the unaffected eye were observed to have lower flows at night than during the day. Isoproterenol had no significant effect on flow during the day in normal eyes or in Horner's syndrome, but during sleep this beta-adrenergic agonist increased flow in the normal eye by 34% and in the Horner's eye by 50%. We interpret the results as indicating that beta-adrenergic activity in the human eye can stimulate aqueous formation under some conditions. However, the observed stimulation could have been due to something other than increased beta-adrenergic activity in the ciliary epithelium.

Adrenergic beta-Agonists↗
PubMed1987

cDNA cloning and complete primary structure of the alpha subunit of a leukocyte adhesion glycoprotein, p150,95.

The leukocyte adhesion receptors, p150,95, Mac-1 and LFA-1 are integral membrane glycoproteins which contain distinct alpha subunits of 180,000-150,000 Mr associated with identical beta subunits of 95,000 Mr in alpha beta complexes. p150,95 alpha subunit tryptic peptides were used to specify oligonucleotide probes and a cDNA clone of 4.7 kb containing the entire coding sequence was isolated from a size-selected myeloid cell cDNA library. The 4.7-kb cDNA clone encodes a signal sequence, an extracellular domain of 1081 amino acids containing 10 potential glycosylation sites, a transmembrane domain of 26 amino acids, and a C-terminal cytoplasmic tail of 29 residues. The extracellular domain contains three tandem homologous repeats of approximately 60 amino acids with putative divalent cation-binding sites, and four weaker repeats which lack such binding sites. The cDNA clone hybridizes with a mRNA of 4.7 kb which is induced during in vitro differentiation of myeloid cell lines. The p150,95 alpha subunit is homologous to the alpha subunits of receptors which recognize the RGD sequence in extracellular matrix components, as has previously been shown for the beta subunits, supporting the concept that receptors involved in both cell-cell and cell-matrix interactions belong to a single gene superfamily termed the integrins. Distinctive features of the p150,95 alpha subunit include an insertion of 126 residues N-terminal to the putative metal binding region and a deletion of the region in which the matrix receptors are proteolytically cleaved during processing.

Amino Acid Sequence↗
PubMed1986

Chemical modification of bovine prothrombin fragment 1 in the presence of Tb3+ ions.

The formaldehyde-morpholine method for the conversion of gamma-carboxyglutamyl (Gla) residues to gamma-methyleneglutamyl (gamma-MGlu) residues has been applied to the modification of bovine prothrombin fragment 1. In the absence of Tb3+ ions or at Tb3+ ion concentrations of 2 Km app and 25 Km app the action of 10,000-fold molar excess of formaldehyde and morpholine, pH 5.0, converts the 10 Gla residues of the protein into 10 gamma-MGlu residues. Modification of the protein using the same conditions but increasing the Tb3+ concentration to 100 Km app provided a homogeneous protein containing 3 gamma-MGlu and 7 Gla residues, bovine 3 gamma-MGlu-fragment 1. The modified protein binds the same number of Ca2+ ions (6-7) as bovine fragment 1. However, the positive cooperatively associated with Ca2+ binding is abolished and the overall affinity for Ca2+ ions is reduced. Fluorescence titrations of 3 gamma-MGlu-fragment 1 using either Ca2+ or Mg2+ ions indicate that the modified protein retains a fluorescence quenching behavior similar to that of the native protein. The modified protein does not bind to phosphatidylserine/phosphatidylcholine vesicles in the presence of Ca2+ ions. Thus the metal ion-induced fluorescence transition exhibited by the bovine protein appears to be a necessary but not sufficient condition for phospholipid binding.

Amino Acids↗
PubMed1986

A partial genomic DNA clone for the alpha subunit of the mouse complement receptor type 3 and cellular adhesion molecule Mac-1.

A genomic clone coding for the alpha subunit of the mouse complement receptor type 3 and the cellular adhesion molecule Mac-1 has been isolated directly from a genomic library using synthetic oligonucleotide probes based on the amino-terminal amino acid sequence of the protein. The identity of the clone has been established by DNA sequencing and in vitro translation of hybrid-selected mRNA. The gene is present in a single copy in the murine genome. The region containing the amino-terminal exon has been sequenced. RNA gel blotting shows that the Mac-1 alpha-subunit mRNA is 6 kilobases in length. Mac-1 alpha-subunit mRNA is present in macrophages but not T lymphoma or L cells. During gamma interferon-stimulated maturation of the mouse premyelocytic cell line M1, Mac-1 alpha-subunit mRNA is induced. This corresponds with the tissue distribution of the Mac-1 alpha subunit, showing expression is regulated at least partially at the message level.

Animals↗
PubMedDate not supplied

Physicochemical characterization of poly(ethylene glycol)-modified anti-GAD antibodies.

Monoclonal antibodies against glutamic acid decarboxylase (anti-GAD) were modified with poly(ethylene glycol) (PEG), and the resulting conjugates were characterized. Monoclonal anti-GAD antibodies were purified from ATCC HB184 hybridoma cells by either cell culture supernatant or ascites fluid from BALB/c mice. Polyclonal rabbit IgG antibodies were also used as a model protein. Polyclonal rabbit IgG or purified anti-GAD was modified by PEG (MW = 5000 or 20000 Da) through either the lysine residues or through the carbohydrate moiety. Lysine modification was performed in PBS (pH 7.4) or 0.1 M borate (pH 9.2) by adding a molar excess (5-80) of a succinimidyl activated propionic acid terminated mPEG (SPA-PEG) while stirring at room temperature. Carbohydrate modifications were performed in PBS (pH 6.2) by first oxidizing the antibody with sodium periodate followed by incubation with hydrazide-terminated PEG followed by reduction with sodium cyanoborohydride. The degree of modification was assessed by 1H NMR or TNBS (trinitrobenzenesulfonic acid). Circular dichroism (CD) spectra were obtained for lysine-modified rabbit IgG at various degrees of modification ranging from 5 to 60 PEG per antibody. Binding was assessed using an ELISA method with GAD or rabbit anti-mouse-IgG (H+L) coated plates. The TNBS and 1H NMR analysis of the modified antibody showed reasonably similar results from 5 to 60 PEG per antibody. The 1H NMR method showed greater sensitivity at low modifications (below 20:1) and was fairly linear up to about 60 PEG per antibody. The CD spectra of the polyclonal rabbit IgG showed only small differences at variously modified antibody. The binding affinity of anti-GAD is lower for all PEG modifications with respect to unmodified anti-GAD. Modifications at pH 7.4 show lower binding to GAD than modifications at pH 9.2. Binding to GAD or anti-mouse-IgG is decreased as the degree of modification is increased. Lysine modifications showed lower binding to GAD or anti-mouse-IgG than carbohydrate modifications. Binding to GAD or anti-mouse-IgG is lower for PEG20000-modified anti-GAD with respect to PEG5000-modified anti-GAD.

Antibodies, Anti-Idiotypic↗
PubMedDate not supplied

Cutting edge technologies in the evaluation of bone marrow samples.

OBJECTIVE: To review cutting edge technologies for evaluation of bone marrow samples. DATA SOURCES: Professional literature and authors' experience. DATA SYNTHESIS: Novel technologies for evaluating bone marrow specimens that have prognostic and therapeutic value in chronic and acute leukemia have been recently developed. Polymerase chain reaction-based assays that are useful in detecting chromosomal translocations in CML and AML are relevant to diagnosis and initial therapy. These assays can also be used to detect minimal residual disease after therapy and thus have prognostic value. In addition, a novel and elegant technique for determining leukemic cell resistance to chemotherapy agents (in vitro drug sensitivity) has prognostic and therapeutic value in AML. Use of these assays may lead to greater diagnostic precision, improved prognostication and more effective therapy. CONCLUSION: Cutting edge technologies that have utility in the evaluation of bone marrow specimens include polymerase chain reaction based assays for detecting specific chromosomal translocations, particularly useful in CML and AML, as well as in vitro drug sensitivity testing in AML.

Acute Disease↗
PubMedDate not supplied

Viscoelastic agents.

Viscoelastic materials possess a unique set of properties that result from their chemical structure. These properties enable them to protect the corneal endothelium and epithelium from mechanical trauma and to maintain an intraocular space, such as the anterior or vitreous chambers, even in the face of an open incision. Hence viscoelastic materials have been successfully applied to many areas of ophthalmic surgery, most notably anterior segment surgery, with few complications. There are currently three commercially available viscoelastic preparations, and several new preparations are in various stages of development.

Acrylic Resins↗
PubMedDate not supplied

Chromosome fragile sites in mentally retarded males: increased incidence with seizures and diphenylhydantoin therapy.

Chromosome fragile site or lesion data were examined in 154 institutionalized mentally retarded males with or without seizures or treated with anti-seizure medication. Blood lymphocytes were cultured using three different cell culture conditions and the incidence of specific chromosome fragile sites (10q25, 16q22, and 12q23) or lesions determined. Increased fragile sites were seen in mentally retarded males with seizures compared to those without seizures in cells grown in folate-deplete Medium 199. Those with seizures and treated with diphenylhydantoin had a higher incidence of induced fragile sites (p < 0.001) relative to similar patients treated with anti-seizure medication other than diphenylhydantoin. These results suggest that a cohort of patients with mental retardation and seizures are more likely to have induced cytogenetic changes when treated with diphenylhydantoin than mentally retarded individuals without seizures.

Adolescent↗