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Biomedical subjects

M Lundström

Publications and source records attributed to M Lundström.

At least 55 records · Page 3Linked to original sources

Host cell-induced differences in O-glycosylation of herpes simplex virus gC-1. I. Structures of nonsialylated HPA- and PNA-binding carbohydrates.

Lectins with narrow oligosaccharide specificities were established as probes to study the host cell influence on the biosynthesis of O-linked oligosaccharides of the herpes simplex virus type 1 (HSV-1)-specified glycoprotein C (gC-1). We found that only gC-1 and no other glycoprotein bound to the peanut lectin (PNA), with main specificity for Gal(beta 1-3)GalNAc. Previously, we have shown that only gC-1 binds to the Helix pomatia lectin (HPA), with main specificity for terminal GalNAc. The O-linked oligosaccharides binding to PNA and HPA were released by alkaline borohydride treatment and characterized. A structural determination of these oligosaccharides showed that the HPA-binding carbohydrates were monosaccharides (GalNAc), and that the PNA-binding oligosaccharides were disaccharides with the structure Gal-GalNAc. The PNA- and HPA-binding oligosaccharides were arranged as Pronase-resistant clusters on gC-1, consisting of about seven individual, adjacent oligosaccharides. In addition to these disaccharides, Pronase-resistant PNA-binding glycopeptides of gC-1 also contained neutral trisaccharides. Larger O-linked oligosaccharides, binding to the wheat germ lectin, were found in gC-1, but not in proximity to the PNA-binding ones. It was concluded that the lectins mentioned should be useful probes in screening HSV-infected cells of different lineages for differences in processing of O-linked oligosaccharides.

Cell Line↗

Host cell-induced differences in the O-glycosylation of herpes simplex virus gC-1. II. Demonstration of cell-specific galactosyltransferase essential for formation of O-linked oligosaccharides.

By using a lectin-based screening method for cell-dependent variations of O-glycosylation of viral glycoprotein, we found that O-linked oligosaccharides of herpes simplex virus type 1 (HSV-1) glycoproteins in virus-infected mouse neuroblastoma (C1300) cells differed from those of HSV glycoproteins produced in other cells. Thus, O-linked oligosaccharides of HSV-1-specified glycoprotein C (gC-1), produced in GMK cells and a number of other cells, occurred mainly as trisaccharides or larger structures. In contrast, gC-1, produced in C1300 cells, contained O-linked monosaccharides and very few, if any, larger oligosaccharides of this class. A structural comparison between O-linked oligosaccharides of gC-1 from HSV-1-infected C1300 cells and from GMK cells showed that biosynthesis was interrupted prior to formation of a core disaccharide with terminal galactose, indicating a major early defect in O-glycosylation of glycoproteins in C1300 cells. A comparison of the content of galactosyltransferases between C1300 and GMK cells showed that C1300 cells lacked galactosyltransferases, including the specific enzyme engaged in formation of the core O-linked disaccharide mentioned, while other glycosyltransferases adding terminal sugars to O-linked oligosaccharides were present in equal amounts in both cell lines. These results indicated that HSV-1 is strictly dependent on host cell-specified factors for biosynthesis of O-linked oligosaccharides associated with viral glycoproteins.

Animals↗

Expression of an interferon-alpha gene variant in E. coli using tandemly repeated synthetic ribosomal binding sites.

A human interferon-alpha 2 gene variant was expressed in Escherichia coli under the control of the tryptophan operon promoter and of a series of synthetic partially overlapping ribosomal binding sites, which control initiation of translation. Variation in the distance between the start codon and such a set of ribosomal binding sites affected the level of interferon expression much less than previously described for single ribosomal binding sites.

Base Sequence↗

Demonstration and mapping of highly carbohydrate-dependent epitopes in the herpes simplex virus type 1-specified glycoprotein C.

The carbohydrate dependence of epitopes in the herpes simplex virus type 1-specified glycoprotein C (gC) was studied using a new solid-phase assay procedure. Glycoprotein C, coated on 96-well microtitre plates, was treated with sialidase and increasing concentrations of periodate. A sequential removal of peripheral monosaccharides from the oligosaccharides of gC was ascertained by an enzyme-linked lectin assay. By using a panel of gC-specific monoclonal antibodies in ELISA, it was found that gC contained two types of epitopes differing in their dependence on terminal galactose and sialic acid for expression. Control experiments indicated that the carbohydrate-dependent epitopes were peptide structures and that the carbohydrates did not directly participate in the antibody-binding reaction. The carbohydrate-dependent epitopes were mapped to antigenic site II, according to the proposed nomenclature, whereas those expressed also in the absence of peripheral sugars were located mainly in antigenic site I. These results were compatible with the relative distribution of oligosaccharides in the gC molecule.

Antibodies, Monoclonal↗

Interleukin-2 versus phorbol-ester-induced cellular events in normal T-lymphocytes.

Activation of primary T-lymphocytes (T-cells) is dependent on interactions with the T3/T-cell antigen receptor complex which results in expression of cell surface receptors for the lymphocytotrophic growth factor interleukin-2 (IL-2). In the present communication we have compared the cellular responses to phorbol ester with IL-2-induced cellular responses. Thus, the effect of respective ligand on T-cell growth, the level of expression and composition of two distinct affinity classes of IL-2 receptors, and phosphorylation of an 80,000 mol. wt cellular substrate for the Ca2+-dependent, phospholipid-dependent protein kinase C (PK-C) was analysed. The results demonstrate that only the high affinity IL-2 receptor class is induced by phorbol esters and that both IL-2 and cell surface expression of its high affinity receptor is required for induction of low affinity IL-2 receptors. Moreover, IL-2 receptor signalling seems not to involve activation of PK-C and the results suggest that another intracellular pathway, distinct from the PK-C pathway which induces high affinity IL-2 receptors, is employed in the transmission of IL-2 growth promoting signals.

Cells, Cultured↗

Calcium-independent release of gamma-aminobutyrate from nerve processes in the developing rabbit retina.

Retinas from 3- and 10-day-old rabbits, and from young (29 days), or adult animals were used to study in parallel the development of synaptic vesicles in amacrine cells and the Ca2+ dependence of the K+-stimulated [3H]gamma-aminobutyrate release from them. Few synaptic vesicles were observed in the amacrine cell processes in retinas from the 3-day-old rabbits. The number of vesicles significantly increased between 3 and 10 days and increased further between day 10 and the adult animal. The Ca2+ dependence of the K+-stimulated release decreased with increasing age. There is thus a poor correlation between the Ca2+ dependent transmitter release and the number of synaptic vesicles in the nerve terminal, favouring the existence of a Ca2+ dependent nonvesicular process for the [3H]gamma-aminobutyrate release in the rabbit retina.

Aging↗

Characterization of a herpes simplex virus type 2-specified glycoprotein with affinity for N-acetylgalactosamine-specific lectins and its identification as g92K or gG.

Extracts from herpes simplex virus type 2 (HSV-2)-infected cells were subjected to affinity chromatography with gel-bound Helix pomatia lectin (HPA). Only one HSV-2-specified glycoprotein was isolated by this procedure and the glycoprotein had an apparent molecular weight of 130 000 (130K). The HPA-binding glycoprotein was genetically mapped, using HSV-1 X HSV-2 intertypic recombinants into the short component of the HSV-2 genome. The mapping position, electrophoretic mobility and the antigenic properties of the HPA-binding protein indicated that it was unrelated to glycoprotein C (gC), which is the HPA-binding glycoprotein in HSV-1-infected cells, and distinct from gE and gD which map in the S component. The glycoprotein was almost quantitatively precipitated by monoclonal antibody AP1, specific for glycoprotein g92K and it also reacted with monoclonal antibody 1206-3, specific for the HSV-2 glycoprotein G previously described. It is concluded that the isolated glycoprotein is identical to g92K and consequently also to the HSV-2-specific glycoprotein G.

Acetylgalactosamine↗

Different populations of herpes simplex virus glycoprotein C discriminated by the carbohydrate-binding characteristics of N-acetylgalactosamine specific lectins (soybean and Helix pomatia). Brief report.

From the herpes simplex virus specified glycoprotein C two fractions were isolated with affinity either for Helix pomatia lectin (HPA) or soybean lectin (SBA). The data indicated that HPA and SBA, despite their mutual main specificity for N-acetylgalactosamine, recognize structurally different gC populations.

Acetylgalactosamine↗

The antiherpes drug (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdU) interferes with formation of N-linked and of O-linked oligosaccharides of the herpes simplex virus type 1 glycoprotein C.

In HSV-1 infected cell the antiherpes drug (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdU) exerted at least three different effects on glycosylation of glycoprotein gC. First, an overall decrease of protein glycosylation occurred due to inhibition of synthesis of the lipid-linked oligosaccharides, precursors of N-linked oligosaccharides of gC. Second, an inhibition of processing of N-linked oligosaccharides occurred after the acquisition of endo H-resistance, and possibly due to inhibition of galactose incorporation. Third, a small inhibition of incorporation of glucosamine into O-linked oligosaccharides, and, may be associated with this, a change in the proportion of two different classes of O-linked oligosaccharides of gC, namely those with terminal N-acetylgalactosamine and those with terminal sialic acid.

Antiviral Agents↗

Glycoprotein C of herpes simplex virus type 1: characterization of O-linked oligosaccharides.

In contrast to other viral glycoproteins, the herpes simplex virus (HSV) glycoprotein C(gC) binds to the N-acetylgalactosamine-specific Helix pomatia lectin (HPA). In the present paper gC was purified by affinity chromatography with monospecific antibodies and the purified glycoprotein was subjected to protease digestion. HPA-binding protease-resistant glycopeptides were isolated by lectin affinity chromatography. The isolated structures did not bind to concanavalin A and seemed to lack charged groups as determined by ion-exchange chromatography. In gel filtration, the glycopeptides appeared in two peaks with molecular weights higher than 4000. The HPA-binding structures of gC were synthesized in the presence of tunicamycin, indicating that they belong to the O-glycosyl class of oligosaccharides. In addition to HPA-binding oligosaccharides, synthesis of tunicamycin-resistant wheat germ lectin-binding gC oligosaccharides was demonstrable. These were sensitive to sialidase and apparently unrelated to the HPA-binding oligosaccharides.

Chromatography, Affinity↗

Computer densitometry of retinal nerve fibre atrophy. A pilot study.

Lack of nerve fibre layer opacity and a granular appearance of the retina are important funduscopic signs in optic atrophy. In this pilot study serially obtained fundus photographs from a case with developing optic atrophy where subjected to computer densitometry. A monotonic increase in local density variations was found during evolution of optic atrophy. The change in density variations closely followed the funduscopic change in nerve fibre layer opacity. This method makes it possible to detect and quantify diffuse atrophy of the retinal nerve fibre layer.

Adult↗

330 trabeculectomies. A long time study (3-5 1/2 years).

281 eyes out of 330 were followed during 3 to 5 1/2 years after trabeculectomy. 32 eyes were drop-outs due to death and 17 eyes due to inability to participate in the examination program. The mean age at time of surgery was 66 years. A mean pre-operative IOP of 31 mmHg dropped to a mean post-operative level of 18 mmHg. In 57% a single trabeculectomy was considered enough to control the glaucoma. Post-operative medical treatment was considered necessary in 35%. In 87% the pre-operative progress of the field defect was arrested. A reoperation was performed in 8%. The early complications were very few, but in 25% slowly developing cataract was observed. A cataract extraction was performed in 29 eyes post trabeculectomiam with a favourable visual outcome. This study confirms the opinion that trabeculectomy is an atraumatic and efficient surgical procedure and a necessary therapeutic measure when the tolerable combination of antiglaucoma drugs proves insufficient to control the glaucoma.

Aged↗

Anorexia nervosa and polymorphonuclear (PMN) granulocyte reactions.

10 patients with anorexia nervosa were compared with controls with normal weight, regarding their peripheral blood polymorphonuclear (PMN) granulocyte reactions. The anorexia patients showed a statistically significant decrease in PMN bactericidal capacity and PMN adherence. The mean chemotaxis did not differ, but in two of the anorexia patients chemotaxis was almost absent. The intracellular activity of alkaline phosphatase was below the reference values in 5 of the 6 patients in whom it was investigated. It is concluded that changes in granulocyte function may be noted in anorexia nervosa, but their clinical significance is uncertain, as no patients had recurrent or severe infectious diseases.

Adolescent↗

Atrophy of optic nerve fibres in compression of the chiasm. Prognostic implications.

A relationship between the degree of atrophy of retinal nerve fibres and visual field defect has been described in postoperative steady-state patients (Lundström & Frisén 1976). The same factors were studied prior to surgery in six patients with compression of the chiasm due to chromophobe adenoma. In five eyes the field defect was excessive in relation to the degree of atrophy. After surgery the visual field defects improved to a level corresponding to the degree of atrophy in these eyes. In the remaining seven eyes there was a close correspondence between the atrophy and the visual field defect already before surgery. The visual field defects remained unchanged in these eyes. Provided that atrophy does not increase after surgery, simultaneous preoperative evaluation of retinal nerve fibre atrophy and visual field defect allows an accurate prediction of prognosis for improvement.

Adenoma, Chromophobe↗

Atrophy of optic nerve fibres in compression of the chiasm. Observer variation in assessment of atrophy.

Different observers' assessment of atrophy according to a semi-quantitative method was analysed. Five observers scored the degree of atrophy on magnified black-and-white fundus photographs from normal controls and from patients with chiasmal lesions of different severity. Four of the five examiners achieved a reasonably uniform assessment of atrophy. The results of the test prompted some modification in the grading system.

Adenoma, Chromophobe↗

330 trabeculectomies--a follow-up study through 1/2-3 years.

In 1967 a new microsurgical procedure for glaucoma known as trabeculectomy was introduced. This method is reported to have few early complications and a good pressure-reducing effect. Our material presents the results of 330 consecutive trabeculectomies with a follow-up period of 1/2-3 years. The following items are discussed: IOP, visual acuity, visual fields, surgical complications, and need of re-operation and medical postoperative therapy. We conclude that trabeculectomy is a safe and efficient antiglaucoma operation, recommended as an attractive alternative to heavy medication.

Evaluation Studies as Topic↗

Trabeculectomy combined with cataract extraction.

In a combined trabeculectomy and cataract extraction procedure on 17 eyes of 16 patients, there was a 50% average decrease in intraocular pressure. Visual acuity improved in 14 eyes, remained unchanged in two eyes, and declined in one eye. The postoperative complications were few and appreciable in only two cases. According to our follow-up findings, the combined technique is no more traumatic than an ordinary cataract extraction.

Aged↗

Atrophy of optic nerve fibres in compression of the chiasm. Degree and distribution of ophthalmoscopic changes.

Chiasmal lesions produce a characteristic form of partial optic atrophy, subtly reflected by objective changes in the peripapillary portion of the retinal nerve fibre layer. The degrees and distributions of these changes were documented by fundus photography in a series of steady state patients with different degrees of chiasmal damage from pituitary adenoma. Semi-quantitative analysis disclosed a close correspondence with the degree of functional deficit. The state of the retinal nerve fibre layer can therefore be used as an objective indicator of the occurrence and severity of anatomical, chiasmal damage.

Adult↗