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Biomedical subjects

M Olsen

Publications and source records attributed to M Olsen.

At least 55 records · Page 3Linked to original sources
PubMed1995

The ability to re-express polysialylated NCAM in soleus muscle after denervation is reduced in aged rats compared to young adult rats.

The neural cell-adhesion molecule, NCAM, contains an unusual homopolymer of sialic acid units, polysialic acid. This carbohydrate seems to be involved in neurite outgrowth, bundling and branching, processes which are important during reinnervation. In aged rats, reinnervation of denervated muscle fibres is incomplete. In this study, age-related changes in the degree of polysialylation of NCAM re-expressed after denervation were examined using a monoclonal antibody recognizing polysialic acid and a polyclonal antibody recognizing NCAM. The results show that, after denervation, the degree of polysialylation on NCAM was clearly reduced in rat soleus muscle of aged, compared to young, adult rats. This age-related change in expression of polysialic acid probably influences the reinnervation process in aged muscle.

Animals↗
PubMed1995

Use of the rhesus monkey as an experimental model to test the degree of efficacy of an anti-sporozoite peptide malaria vaccine candidate combined with copolymer-based adjuvants.

Humoral response against sporozoites is not effective in protecting individuals from getting malaria. Reduction in the infectivity of sporozoites has not been quantified for most anti-sporozoite vaccines tested. Quantification requires animal models providing predictable prepatent periods, e.g., time elapsed between sporozoite inoculation and detection of parasitemia, to be used as an indicator of activity against sporozoites. A delay in prepatent period from vaccinated animals would therefore reflect a protective effect in reducing the number of parasites. We report the vaccination of rhesus monkeys with a synthetic peptide reproducing part of the repeated region of the circumsporozoite protein of Plasmodium cynomolgi. This peptide was conjugated to the carrier protein diphtheria toxoid and injected with four adjuvant formulations that differed only by the type of emulsion or immunomodulator. Because all five control animals had a synchronous prepatent period after challenge with live sporozoites, it was possible to quantify the protective efficacy for each vaccine formulation, even though all monkeys developed parasitemia. Sporozoite elimination correlated with the immunomodulator and the type of emulsion. Such elimination was related neither to antibody titer against the immunizing peptide or the whole sporozoite, nor to antibody isotype induced by the vaccine formulation.

Adjuvants, Immunologic↗
PubMed1994

A quantitative assay to measure the interaction between immunogenic peptides and purified class I major histocompatibility complex molecules.

A direct and sensitive biochemical assay to measure the interaction in solution between peptides and affinity-purified major histocompatibility complex (MHC) class I molecules has been generated. Specific binding reflecting the known class I restriction of cytotoxic T cell responses was obtained. Adding an excess of beta 2-microglobulin (beta 2m) significantly increased the rate of peptide association, but it did not affect the rate of dissociation. Binding was complicated by a rapid and apparently irreversible loss of functional MHC class I at 37 degrees C which might limit the life span of empty MHC class I thereby preventing the inadvertent exchange of peptides at the target cell surface. All class I molecules tested bound peptides of the canonical octa- to nona-meric length. However, one class I molecule, Kk, also bound peptides, which were much longer suggesting that the preference of class I molecules for short epitopes is not absolute and may be caused by factors other than the peptide-MHC class I binding event itself.

Amino Acid Sequence↗
PubMed1994

An unusual cystic lesion histologically similar to autosomal dominant polycystic kidney disease in a child with aniridia and del 11p13.

The association of Wilms tumor with an interstitial deletion on the short arm of chromosome 11 is well established. Specifically, the 11p13 band has been implicated in the syndrome of Wilms tumor, aniridia, genitourinary abnormalities and mental retardation. Only rarely have other renal lesions been associated with the chromosomal abnormality del 11p13. We report a case of a segmental cystic lesion, histologically akin to autosomal dominant polycystic kidney disease, in a child with aniridia and the del (11)(p12p14) karyotype.

Aniridia↗
PubMed1993

Intact transmembrane isoforms of the neural cell adhesion molecule are released from the plasma membrane.

Three soluble neural cell adhesion molecule (NCAM) polypeptide classes of M(r) values 190,000 (NCAM-s1), 135,000 (NCAM-s2) and 115,000-110,000 (NCAM-s3) have been demonstrated in rat brain and cerebrospinal fluid [Krog, Olsen, Dalseg, Roth and Bock (1992) J. Neurochem. 59, 838-847]. NCAM-s3 is known to arise from released glycosylphosphatidylinositol (GPI)-linked NCAM [He, Finne and Goridis (1987) J. Cell. Biol. 105, 2489-2500] as well as from extracellularly cleaved transmembrane NCAM isoforms [Nybroe, Linnemann and Bock (1989) J. Neurochem. 53, 1372-1378]. In this study the origin of NCAM-s1 and NCAM-s2 and the function of soluble NCAM forms were investigated. It was shown that all three soluble forms could be released from brain membranes with M(r) values identical to the three major membrane-associated forms: the large transmembrane 190,000-M(r) form (NCAM-A), the smaller transmembrane 135,000-M(r) form (NCAM-B) and the GPI-anchored 115,000-110,000-M(r) form (NCAM-C). A polyclonal antibody, directed against transmembrane and cytoplasmic epitopes common to NCAM-A and NCAM-B, was shown to react with NCAM-s1 and NCAM-s2. Furthermore, NCAM-B was shown to be shed in a presumably intact soluble form from membranes of cells transfected with this isoform. Thus, NCAM-s1 and NCAM-s2 probably represent intact released transmembrane NCAM-A and NCAM-B. The soluble transmembrane forms are likely to exist in vivo, as NCAM-s1 and NCAM-s2 were readily demonstrated in cerebrospinal fluid. By density-gradient centrifugation it was shown that shed transmembrane NCAM-B was present in fractions of high, as well as low, density, indicating that a fraction of the shed NCAM is associated with minor plasma membrane fragments. Finally, it was shown that isolated soluble NCAM inhibited cell binding to an immobilized NCAM substratum, attributing a pivotal role to soluble NCAM in vivo as a modulator of NCAM-mediated cell behaviour.

Animals↗
PubMed1993

Age-related changes in expression of the neural cell adhesion molecule in skeletal muscle: a comparative study of newborn, adult and aged rats.

Neural cell adhesion molecule (NCAM) is expressed by muscle and involved in muscle-neuron and muscle-muscle cell interactions. The expression in muscle is regulated during myogenesis and by the state of innervation. In aged muscle, both neurogenic and myogenic degenerative processes occur. We here report quantitative and qualitative changes in NCAM protein and mRNA forms during aging in normal rat skeletal muscle. Determination of the amount of NCAM by e.l.i.s.a. showed that the level decreased from perinatal to adult age, followed by a considerable increase in 24-month-old rat muscle. Thus NCAM concentration in aged muscle was sixfold higher than in young adult muscle. In contrast with previous reports, NCAM polypeptides of 200, 145, 125 and 120 kDa were observed by immunoblotting throughout postnatal development and aging, the relative proportions of the individual NCAM polypeptides remaining virtually unchanged at all ages examined. However, changes in the extent of sialylation of NCAM were demonstrated. Even though the relative amounts of the various NCAM polypeptides were unchanged during aging, distinct changes in NCAM mRNA classes were observed. Three NCAM mRNA classes of 6.7, 5.2 and 2.9 kb were present in perinatal and young adult skeletal muscle, whereas only the 5.2 and 2.9 kb mRNA classes could be demonstrated in aged muscle. This indicates that metabolism of the various NCAM polypeptides is individually regulated during aging. Alternative splicing of NCAM mRNA in skeletal muscle was studied by Northern blotting using DNA oligonucleotide probes specifically hybridizing to selected exons or exon combinations. Exon VASE, which has previously been shown to be present in both brain and heart NCAM mRNA, was virtually absent from skeletal muscle at all ages studied. In contrast, the majority of NCAM mRNA in postnatal skeletal muscle was shown to contain extra exons inserted between exons 12 and 13. Of the various possible exon combinations at this splice site, the combinations 12-a-AAG-13 and 12-a-b seemed to be prevalent in postnatal skeletal muscle. No significant change in the relative proportion of these two exon combinations occurred during aging. The observed upregulation of NCAM protein in aged muscle supports the assumption that an increasing proportion of muscle fibres are denervated in aged muscle. Selective upregulation of the 5.2 and 2.9 kb mRNA forms have previously been demonstrated in muscle cell lines and in primary cultures of muscle cells during formation of myotubes in vitro, and this switch in NCAM mRNA classes has been suggested to correlate with myogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase.

An intronless gene encoding an additional human serotonin (5-HT) 5-HT1-like receptor subtype was isolated from a human genomic library with probes obtained from degenerate PCR primers used to amplify 5-HT-receptor-specific sequences. The highest degree of homology was found with the 5-HT1E subtype (70%) and the 5-HT1D alpha (63%) and 5-HT1D beta (60%) receptors. RNA for this gene was detected in the human brain but was not detected in kidney, liver, spleen, heart, pancreas, and testes. High-affinity (Kd = 9.2 nM) 3H-labeled 5-HT binding was detected. Competition studies revealed the following rank order of potencies for serotonergic ligands: 5-HT > sumatriptan >> 5-carboxyamidotryptamine > 8-hydroxy-2(di-1-propylamino)tetralin > spiperone. 5-HT produced a dose-dependent inhibition of forskolin-stimulated cAMP accumulation (EC50 = 7.9 nM) in transfected cells. These properties distinguish this receptor from any previously characterized and establish a fifth 5-HT1-like receptor subtype (5-HT1F) coupled to the inhibition of adenylate cyclase.

Adenylyl Cyclase Inhibitors↗
PubMed1993

Transfer of ochratoxin A from lactating rats to their offspring: a short-term study.

A dose-dependent transfer of ochratoxin A into the milk of lactating rats was found after a single oral dose of ochratoxin A, given in the dose levels of 10, 50, and 250-micrograms ochratoxin A/kg body weight by gastric intubation. The milk/blood concentration ratio of ochratoxin A at 24 and 72 h was 0.4 and 0.7, respectively. A linear relationship was found between the concentration of ochratoxin A in the dam's milk and in the blood of the pups at 72 h, as well as in the dam's milk and in the kidneys of the pups. The pup blood/milk concentration ratio of ochratoxin A was approximately 6. At 72 h the sucklings had higher levels of ochratoxin A than their dams in both blood and kidneys. The results show that the concentration of ochratoxin A in milk can be used as an indicator of the continuously administered dose to the suckling.

Animals↗
PubMed1993

Expression of NCAM mRNA and polypeptides in aging rat brain.

In aging brain, degenerative as well as compensatory regenerative processes are believed to occur. The neural cell adhesion molecule NCAM is involved in developmental and regenerative processes in the brain. However, the role of NCAM in aging brain has not been characterized. In this study, the expression of NCAM mRNAs and polypeptides was investigated in aging rat brain. The 7.4 and 6.7 kb NCAM mRNAs were selectively downregulated during postnatal development, and the 5.2 and 2.9 kb NCAM mRNAs were upregulated. However, from postnatal day 40 to old age no change in NCAM mRNA classes was observed. The fraction of NCAM mRNA containing the VASE exon increased postnatally but remained stable during adult life. VASE, which is believed to modulate the binding capacity, seemed to be relatively more abundant in the 7.4 and 6.7 kb NCAM mRNAs, encoding transmembrane NCAM forms, than in the 5.2 and 2.9 kb NCAM mRNAs, coding for glycosyl phosphatidylinositol (GPI) linked NCAM. Conversely, insertion of exons a and AAG between exons 12 and 13, a region containing two fibronectin type III repeats, seemed to be more pronounced in 5.2 and 2.9 kb NCAM mRNAs than in the 7.4 and 6.7 kb mRNAs. During postnatal development an increase in the fraction of 6.7 kb NCAM mRNA containing the exons a and AAG was observed. However, during aging the fraction of NCAM mRNAs containing this exon combination seemed constant. At the protein level, NCAM-A was downregulated both during development and aging. No changes were observed during aging in the composition of soluble NCAM forms in the brain, cerebrospinal fluid or blood plasma. The amount of NCAM in rat brain decreased during postnatal development, but remained at a constant level from postnatal day 40 to old age. To conclude, several changes in NCAM expression occur during early postnatal development emphasizing the important role of this molecule in the morphogenetic processes. During aging, a significant selective downregulation of NCAM-A was observed indicating that in general only minor regenerative processes occur in the brain.

Aging↗
PubMed1993

Age-related changes in expression of neural cell adhesion molecule (NCAM) in heart: a comparative study of newborn, adult and aged rats.

The neural cell adhesion molecule (NCAM) has been implicated in cellular interactions involved in cardiac morphogenesis and innervation. In this study, expression of NCAM mRNA and protein was characterized in rat heart during postnatal development and aging (postnatal days 1, 10, 40, 270, and 730). Alternative splicing of NCAM mRNA was analyzed by Northern blotting using DNA oligonucleotide probes designed for demonstration of certain exons or exon combinations. Total NCAM mRNA was downregulated during postnatal development followed by upregulation in the aging heart. Three major NCAM mRNA classes of 6.7, 5.2 and 2.9 kb were expressed in newborn heart in approximately equal proportions. At all other ages, the mRNAs of 5.2 and 2.9 kb were more predominant than the 6.7 kb mRNA. During postnatal development and aging, expression of exon VASE was selectively downregulated in the 6.7 kb NCAM mRNA class, whereas it was clearly detectable in NCAM mRNA classes of 5.2 and 2.9 kb. Insertion of exons a and AAG between exons 12 and 13 was more pronounced in the 5.2 and 2.9 kb NCAM mRNAs than in the 6.7 kb mRNA at all ages. Insertions at the 12/13 junctions decreased in the 6.7 kb mRNA as compared to the 5.2 and 2.9 kb mRNAs during postnatal development. Quantification of NCAM protein by enzyme-linked immunosorbent assay showed that NCAM protein amount decreased from a level of 0.93 microgram NCAM/mg total protein at birth to postnatal day 40 where a level of 0.21 microgram NCAM/mg total protein was found. During aging, NCAM increased again to 0.34 micrograms NCAM/mg total protein at postnatal day 730. NCAM isoforms were studied by immunoblotting analysis. At all ages, the major NCAM isoforms of 190, 145 and 120 kDa were observed in heart, the 145 kDa isoform being predominant.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Bone mass and turnover in fibromyalgia.

Physical inactivity accelerates bone loss. Since patients with fibromyalgia are relatively physically inactive, bone mass and markers of bone metabolism were determined in 12 premenopausal women with fibromyalgia and in healthy age matched female control subjects. No differences were found in lumbar bone mineral density, femoral neck bone mineral density, serum levels of alkaline phosphatase, osteocalcin, ionized calcium and phosphate. The urinary excretion of both hydroxyproline and calcium relative to urinary creatinine excretion was significantly higher in patients with fibromyalgia, p = 0.01. This was linked to lower urinary creatinine excretion (p = 0.02) probably reflecting lower physical activity in the patients with fibromyalgia. We conclude that bone mass and turnover are generally not affected in premenopausal women with fibromyalgia.

Absorptiometry, Photon↗
PubMed1992

Inguinal dermoid cyst presenting as an incarcerated inguinal hernia.

A case of an inguinal dermoid cyst presenting as an incarcerated inguinal hernia in a 18-year-old boy is reported. A differential diagnosis of masses in the inguinal region is discussed and includes not only hernias but also gynecologic and vascular lesions. Dermoid cysts must be included in the differential diagnosis. Histologically, these cysts are characterized by an external lining composed of squamous epithelium with an underlying fibroconnective tissue containing hair follicles, sebaceous, eccrine, and apocrine glands. The presence of all the skin appendages in these cysts distinguishes them from epidermoid and sebaceous cysts. The lack of structures foreign to skin differentiates them from dermoids (benign cystic teratomas) in the ovarian, testicular, retroperitoneal, and sacrococcygeal region.

Abdominal Neoplasms↗
PubMed1992

Characterization of soluble neural cell adhesion molecule in rat brain, CSF, and plasma.

The polypeptide composition and glycosylation of soluble isoforms of neural cell adhesion molecule (NCAM) in developing rat brain, CSF, and plasma were characterized. Soluble NCAM in rat brain consisted of several glycosylated isoforms. The degree of glycosylation was developmentally regulated. After desialylation, four polypeptides of M(r) values of approximately 190,000 (s1), 135,000 (s2), 115,000 (s3), and 110,000 (s4) were observed. Polypeptides s1, s2, and s3 were also present in CSF, whereas only s3 and s4 were observed in plasma. Treatment of soluble brain NCAM with N-glycosidase F, which removes N-linked carbohydrates, produced polypeptides of M(r) values of approximately 190,000, 125,000, and 108,000-97,000. The monoclonal antibody OB11, which recognizes an epitope on the cytoplasmic part of transmembrane forms of NCAM, did not react with any of the soluble isoforms. Purified soluble NCAM, consisting mainly of s3, contained an N-terminal sequence identical to that of membrane-associated NCAM. Gel filtration of s3 indicated that it was present as a dimer under the chosen conditions. NCAM-expressing glioma cells adhered specifically to immobilized soluble NCAM. This implies that functionally significant soluble forms of NCAM are present in the extracellular fluid.

Aging↗
PubMed1991

Effect of thyroxine therapy on bone metabolism in substituted hypothyroid patients with normal or suppressed levels of TSH.

The statement that pituitary hyperthyroidism reflects peripheral hyperthyroidism is still controversial. To evaluate a possible relationship between the calcium and the thyroid metabolism, 29 women with thyroxine (T4) substituted hypothyroidism were examined. They were separated into two groups, one with normal (0.15 to 6 mU/l) and one with suppressed TSH (less than 0.15 mU/l). All the women were judged euthyroid both by their T4 and T3 and by their clinics. The daily dose of T4 (median 0.15 mg in both groups) had been unchanged and TSH level had been stable during the previous six months. Bone mineral content (BMC) of the lumbar spine, bone mineral density (BMD) of left and right collum femoris, serum alkaline phosphatase activity (AP), serum concentration of osteocalcin (Ost) and urinary excretion of hydroxyproline/creatine (Hpr/crea) were similar in the two groups. Furthermore, sex- hormone-binding-globulin (SHBG) was equal in the two groups, but significantly higher than in normals (p less than 0.01). A significant positive correlation was found between serum Ost and Hpr/crea (p less than 0.05) indicating a balanced state where bone formation equals bone resorption. AP failed to correlate to Ost and Hpr/crea because the AP raises from both bone and liver of bone and liver metabolism whereas the two others predominantly reflect bone metabolism. SHBG, being a marker of liver metabolism, was elevated in both groups, probably because of the oral administration of T4. Our data suggest that euthyroid, T4 substituted patients have a normal calcium metabolism whether TSH levels are suppressed or not.

Aged↗
PubMed1991

Adjuvant activity of non-ionic block copolymers. IV. Effect of molecular weight and formulation on titre and isotype of antibody.

The adjuvant activity of block copolymers varies with the lengths of the chains of polyoxypropylene (POP) and polyoxyethylene (POE). This project evaluated the adjuvant activity of new copolymers with long polyoxypropylene chains in mice immunized with TNP-hen egg albumin in 2% squalone-in-water emulsions. Two of the new copolymers, L141 and L180.5, not only stimulated higher antibody titres to TNP than older preparations, but also induced a higher percentage of the IgG2 isotypes. The smaller older copolymers, L101 and L121, induced higher absolute levels of IgG3 antibody and relative increases in IgG1. Incorporation of immunomodulators (cell wall skeletons, monophosphoryl lipid A or threonyl muramyl dipeptide) increased mean IgG titres but also increased variability of responsiveness among individuals.

Adjuvants, Immunologic↗
PubMed1991

Adjuvant activity of non-ionic block copolymers. V. Modulation of antibody isotype by lipopolysaccharides, lipid A and precursors.

Non-ionic block copolymers and lipopolysaccharides are both effective immunological adjuvants which are thought to act via distinct mechanisms. We hypothesized that they might produce synergistic effects when used together. We prepared a series of lipopolysaccharide (LPS) preparations ranging from the smallest precursor, lipid X through complete LPS with O-polysaccharide chains. Three preparations with reduced toxicity, monophosphoryl lipid A, partially hydrolysed Ra-LPS and LPS of Rhodopseudomonas sphaeroides were also utilized. All LPS preparations except the smallest were effective adjuvants for inducing early antibody responses to trinitrophenyl-conjugated hen egg albumin (TNP-HEA) when injected in squalane-in-water emulsions with copolymer L141. Only the larger LPS preparations induced sustained antibody responses. By itself, emulsions of copolymer L141 induced a predominant IgG1 antibody isotype response with lesser amounts of IgG2a and IgG2b. Surprisingly, all of the LPS preparations tested increased the proportion of IgG2 isotypes even though some had little effect on overall titres. The detoxified Ra-LPS (Ra-detox) was the most effective preparation for both increasing antibody titres and inducing the desirable IgG2a and IgG2b isotypes. These results demonstrate that the combination of LPS and block polymer adjuvants can produce synergistic effects without unacceptable toxicities.

Adjuvants, Immunologic↗
PubMed1990

Evidence that protein antigen b of Mycobacterium tuberculosis is involved in phosphate metabolism.

Protein antigen b (Pab) of Mycobacterium tuberculosis has previously attracted interest because of its immunological and diagnostic relevance. In this study we present evidence that Pab possesses a signal sequence and is secreted from the cytoplasm of M. tuberculosis. The synthesis of Pab is enhanced under phosphate starvation indicating that the protein is involved in phosphate metabolism in M. tuberculosis.

Amino Acid Sequence↗