Biomedical subjects

M Larsen

Publications and source records attributed to M Larsen.

At least 37 records · Page 2Linked to original sources

PubMed1998

Objective assessment of photoreceptor displacement and metamorphopsia: a study of macular holes.

BACKGROUND: We have developed a binocular perimetry technique for the quantitative assessment of retinal photoreceptor displacement and metamorphopsia. OBJECTIVE: To study the direction and amplitude of retinal photoreceptor displacement in eyes with idiopathic macular holes using our binocular perimetry technique. SUBJECTS: Five healthy control subjects and 10 patients with unilateral stage 3 to 4 macular holes in one eye and a healthy fellow eye. METHOD: Kinetic perimetry using red and green filter glasses, black binocular fixation targets, red and green selective monocular stimuli (Goldmann III-4-e), and fundus image superimposition of perimetry data. RESULTS: We found no discrepancy between the 2 visual fields in any healthy subjects. In patients with a unilateral macular hole, the central scotoma invariably extended beyond the rim of the hole. In 8 patients, each point on the rim of the scotoma had a perceptually corresponding location in the visual field of the fellow eye that was closer to the center of the visual field. In the 2 patients with the longest duration of symptoms (>2 years), no such discrepancy was found. CONCLUSIONS: Differential perimetry enables the objective study of retinal photoreceptor displacement and metamorphopsia. We found objective evidence for radial centrifugal photoreceptor displacement in most patients with idiopathic macular holes.

Aged↗

PubMed1998

Kluyveromyces lactis killer plasmid pGKL2: evidence for a viral-like capping enzyme encoded by ORF3.

ORF3 of the cytoplasmic linear plasmid pGKL2 was disrupted in vivo by integration of a selectable marker. Long-term cultivation of transformants carrying hybrid plasmids with a disrupted ORF3 under selective pressure did not deprive strains of the native counterpart, thereby proving its essentiality for pGKL2 replication and maintenance. The predicted ORF3 polypeptide was found to contain conserved motifs acquainted with mRNA-capping enzymes in the required order, just as in cytoplasmic viruses; new conserved motifs were also identified.

Acid Anhydride Hydrolases↗

PubMed1998

The effect of acetazolamide on passive and active transport of fluorescein across the blood-retina barrier in retinitis pigmentosa complicated by macular oedema.

BACKGROUND: The carbonic anhydrase inhibitor acetazolamide (AZM) reduces macular oedema in some patients with retinitis pigmentosa. To better understand the oedema-reducing effect of AZM, the effect of AZM on passive permeability and active transport of fluorescein across the blood-retina barrier was studied in patients with retinitis pigmentosa and varying degrees of macular oedema. METHOD: The selection of patients was based on an introductory examination including vitreous fluorometry for qualitative assessment of the vitreous. Macular oedema was graded by fluorescein angiographic leakage. The effect of AZM on the transport properties of the blood-retina barrier was determined by differential spectrofluorometry, in a randomised, double-masked, cross-over study, comprising 2 weeks' treatment with AZM (500 mg/day) and 2 weeks' treatment with placebo. The penetration ratio, defined as the ratio between vitreous concentration 3 mm in front of the retina and the plasma integral, was determined for fluorescein and its metabolite fluorescein glucuronide at 30-60 min and at 120 min after fluorescein injection. Passive permeability and unidirectional permeability in the direction vitreous to blood, due to outward active transport of fluorescein, were determined in those cases where the curves for vitreous concentration of fluorescein could be fitted to a mathematical model. Visual acuity was tested by use of ETDRS standard logarithmic charts. RESULTS: Twenty-two patients volunteered to participate in the study. Signs of significant vitreous detachment/liquefaction caused the exclusion of ten patients after the introductory examination. Nine patients with approximately intact vitreous and varying degrees of oedema completed the cross-over study. AZM treatment was related to a decrease in the penetration ratio of 21% for fluorescein (P=0.01) and of 22% for fluorescein glucuronide (P=0.004). Passive permeability and unidirectional permeability were determined in seven patients. AZM caused a decrease of 27% in the passive permeability of fluorescein (from 1.1 x 10(1) nm/s, P=0.031), and a 95% increase in unidirectional permeability of fluorescein (from 1.2 x 10(2) nm/s, P=0.047). AZM led to a reduction in the grade of macular oedema as determined by fluorescein angiography in three out of seven patients. Only small improvements (< or =5 letters) in visual acuity were noted. CONCLUSION: The present study indicates that the oedema-reducing effect of AZM is due to decreased leakage and stimulated active transport across the blood-retina barrier.

Acetazolamide↗

PubMed1998

Precipitation of hard exudate after resorption of intraretinal edema after treatment of retinal branch vein occlusion.

PURPOSE: To present evidence that precipitation of hard exudate in the retina can occur after reduction of macular edema by successful photocoagulation treatment for retinal branch vein occlusion. METHODS: A 59-year-old woman received argon laser retinal photocoagulation treatment for retinal branch vein occlusion over the primarily involved engorged area of the retina. Fundus changes were documented by fundus photography and optical coherence tomography. RESULTS: Before treatment, an extensive intraretinal edema with cavity formation and a small serous foveal detachment extended outside the engorged area of the retina. Three months after treatment, all retinal thickening had disappeared, but a markedly increased amount of intraretinal hard exudate was seen adjacent to the treated area. CONCLUSIONS: Precipitation of hard exudate can occur after reduction of macular edema by successful retinal photocoagulation treatment, presumably because water and highly soluble electrolytes are resorbed faster than lipids. This phenomenon should be distinguished from accumulation of hard exudate resulting from disease progression.

Chemical Precipitation↗

PubMed1998

Dung-derived biological agents associated with reduced numbers of infective larvae of equine strongyles in faecal cultures.

Two sets of dung-derived organisms from soil routinely fertilized with manure (MA) and soil chemically fertilized (CH) were cultured separately in the laboratory. Baermannized organisms from these cultures were added to 20 g of faeces from strongyle-infected horses to form three treatment groups: (i) no soil organisms; (ii) low inoculum of soil organisms containing all organisms present in a suspension of approximately 100 adult female free-living nematodes; and (iii) high inoculum containing those soil organisms present with approximately 1000 adult female free-living nematodes. Three studies were conducted using MA cultures and faeces containing 50 stronglye epg, CH cultures and faeces containing 1500 strongyle epg, and a mixture of soil organisms from the two cultures (MC) and faeces containing 600 strongyle epg. Within each study, five control cultures and 15 each of low and high inoculum cultures were prepared and incubated at 24 degrees C and 95% humidity in a climate chamber for 15 days. Parasitic and free-living nematodes were then recovered by the Baermann technique and counted. The numbers of third stage larvae were significantly lower in the high inoculum group compared to controls. The percent reductions in the number of third stage larvae for the low and high inoculum groups were 63.6% and 90.9%, 85.1% and 97.1%, 84.5% and 98.4% for MA, CH, and MC studies, respectively, indicating that mortality increased with the number of soil organisms added to cultures. Examination of the source cultures detected the presence of two species of nematophagous fungi and three genera of free-living nematodes reported to be predacious.

Animals↗

PubMed1998

Bilateral optic neuritis in acute human immunodeficiency virus infection.

PURPOSE: To report a case of acute viral disease accompanied by bilateral optic neuritis with substantial paraclinical evidence that human immunodeficiency virus was the causative agent. METHODS: Clinical and paraclinical examination. Magnetic resonance imaging. RESULTS: Virus and antibody titers as well as reverse lymphocytosis were consistent with acute infection by the human immunodeficiency virus-1. CONCLUSIONS: Human immunodeficiency virus infection should be considered in the differential diagnosis of acute optic neuritis.

Acute Disease↗

PubMed1998

Effect of isoflurane on release and uptake of gamma-aminobutyric acid from rat cortical synaptosomes.

We have studied the effect of isoflurane on potassium-evoked release and high-affinity uptake of gamma-aminobutyric acid (GABA) in rat cortical synaptosomes. Isoflurane 1.5% and 3% increased calcium-dependent release by 38% and 36% of control values, respectively (P < 0.05). Calcium-independent release was reduced correspondingly by 24% and 26% (P < 0.05). High-affinity uptake of GABA was not affected by isoflurane. The findings of increased synaptic GABA release combined with unaltered uptake suggest that isoflurane increases GABA in the synaptic cleft and thus may enhance inhibition.

Anesthetics, Inhalation↗

PubMed1998

The effect of isoflurane on brain amino acid release and tissue content induced by energy deprivation.

This article describes the effect of isoflurane on amino acid release and tissue content induced by energy deprivation in slices of rat hippocampus. Energy deprivation (95% N2 / 5% CO2 and glucose free medium) (ED) induced an increase in the release of all amino acids measured, with the exception of glutamine. The tissue content of all amino acids except gamma-aminobutyric acid (GABA) and arginine was concomitantly reduced. Isoflurane (1.5% and 3.0%) reduced glutamate release during ED by 27% and 28% (p < 0.05 as compared with release without isoflurane), respectively, whereas the tissue content was slightly increased. Similarly, GABA release was reduced by 25% and 25% (p < 0.05 as compared with release without isoflurane) accompanied by an insignificant enhancement in tissue content as compared with ED without isoflurane. Isoflurane reduced the release of taurine and most of the other amino acids. The total amount of all amino acids (both released and retained) was not significantly altered by the anesthetic. These observations demonstrate that isoflurane can modify the changes in amino acid handling induced by energy deprivation.

Amino Acids↗

PubMed1998

Survey of anthelmintic resistance on Danish horse farms, using 5 different methods of calculating faecal egg count reduction.

This study reports on the prevalence of anthelmintic resistance in strongyles of horses in Denmark. Of 5 methods used for the calculation of faecal egg count reduction (FECR) the method recommended by the World Association for the Advancement of Veterinary Parasitology, for the detection of resistance in sheep was the most sensitive procedure for detecting resistance. Using this method benzimidazole resistance was detected on 33 of 42 farms (79%) examined. Pyrantel was tested on 15 farms and FECR tests indicate resistance on 3 (30%) farms. On 2 farms on which resistance to pyrantel was detected resistance to benzimidazoles was also detected. On one of 16 farms examined ivermectin resistance was indicated at Day 14 but not at Day 19. On the 15 remaining farms ivermectin was effective. Due to the high prevalence of anthelmintic resistance in Danish horse herds it is recommended that tests of anthelmintic efficacy be conducted routinely to monitor the effectiveness of the strongyle control programmes.

Animals↗

PubMed1998

Impact of mixed strongyle infections in foals after one month on pasture.

Twelve Standardbred foals (age 3-6 months), with little previous exposure to parasites, were allocated to 2 groups and put onto pasture with low (Group L) or high (Group H) levels of larval contamination of large strongyles and cyathostomes. After 4 weeks grazing in September, the foals were housed indoors until necropsy 15 weeks later. Foals in Group H became clinically more affected than those of Group L in that they showed loss of vigour, weight gain depression, intermittent soft faeces and inappetence. One foal of Group H had persistent diarrhoea and was subjected to euthanasia 12 weeks after housing. Signs of colic were not observed. Faecal egg counts were significantly higher in Group H than in Group L (P<0.05). At necropsy, the mean number of S. vulgaris and cyathostomes was 20 and 18,000, respectively, in Group L, and 167 and 25,000 in Group H. Routine blood chemistry did not specifically reveal presence of S.vulgaris in pre-patency. A transient neutrophilia and eosinophilia, most prominent in Group H, was seen 2-8 weeks after start of exposure and anaemia was observed later in Group H. Serum albumin and albumin/globulin ratio were reduced, particularly in Group H, and a marked hyperbetaglobulinaemia was observed at 16-20 weeks in Group H. In conclusion, heavy infections with strongyles including S. vulgaris may become established in weaned foals after a brief period on pasture. Infections may be expressed clinically as debilitation, inappetence and intermittent diarrhoea without colic, and the need for control is imperative.

Analysis of Variance↗

PubMed1998

Localization of transforming growth factor-beta1 and type II receptor in developing normal human prostate and carcinoma tissues.

Transforming growth factor-beta1 (TGF-beta1) is implicated in prostate development, and elevated expression of TGF-beta1 has been correlated with prostate carcinogenesis. In this study, cell type specificity of TGF-beta1 and TGF-beta receptor Type II (RcII) protein expression was determined by immunocytochemistry in human normal prostate and compared to prostate carcinoma tissues. Heterogeneous localization patterns of LAP-TGF-beta1 (TGF-beta1 precursor) and RcII were observed in both epithelial and mesenchymal cells in fetal prostate, with LAP-TGF-beta1 localizing to more basal epithelial cells. Homogeneity of LAP-TGF-beta1 staining was increased in neonatal, prepubertal, and adult prostate, with elevated immunoreactivity noted in epithelial acini relative to stromal tissue for both LAP-TGF-beta1 and RcII proteins. In stromal tissues, RcII cell localization exhibited staining patterns nearly identical to smooth muscle alpha-actin. In prostate carcinoma, LAP-TGF-beta1 localized to carcinoma cells with an increased staining heterogeneity relative to normal prostate. In contrast to normal epithelial cells, carcinoma epithelial cells exhibited low to nondetectable RcII staining. Stromal cell staining patterns for LAP-TGF-beta1 and RcII in carcinoma, however, were identical to those of normal prostate stromal cells. These studies implicate both epithelial and stromal cells as sites of TGF-beta1 synthesis and RcII localization in the developing and adult normal human prostate. In addition, these data indicate a loss of epithelial expression of RcII concurrent with altered LAP-TGF-beta1 expression in human prostate carcinoma cells.

Adolescent↗

PubMed1998

Transforming growth factor-beta1 induces nuclear to cytoplasmic distribution of androgen receptor and inhibits androgen response in prostate smooth muscle cells.

Stromal-epithelial interactions in the prostate gland are dependent on androgen regulation of prostate stromal cells, yet little is known about androgen action in these cell types. Recent reports have demonstrated that androgen-regulated gene transcription can be stimulated or inhibited by certain growth factors, indicating cross-talk mechanisms. To address potential cross-talk in signaling pathways between androgen and transforming growth factor-beta1 (TGFbeta1) in prostate stromal cells, the PS-1 prostate smooth muscle cell line was examined. In the presence of physiological concentrations of androgen, PS-1 cell proliferation was stimulated, and androgen receptor (AR) exhibited a nuclear localization pattern. The addition of TGFbeta1 (25 pM) was capable of blocking androgen-induced proliferation, but had no direct effect in cultures without androgen. Immunocytochemistry to localize AR subcellular distribution showed that TGFbeta1 (5-100 pM) altered the distribution of AR from the nucleus to the cytoplasm. Other growth factors, including fibroblast growth factor-2, epidermal growth factor, and TGFbeta2 had no effect on AR distribution. The TGFbeta1-induced nuclear to cytoplasmic change in receptor localization was rapid (initiated within 30 min), was neutralized by TGFbeta1 antibodies, did not require new protein synthesis, and was complete by 6 h. Removal of TGFbeta1 from the culture medium resulted in a rapid redistribution of AR to the nucleus, indicating reversible mechanisms. Northern analysis of the ddp17 marker transcript for androgen action in PS-1 cells showed that androgen-stimulated ddp17 expression was inhibited in the presence of TGFbeta1 (25 pM). TGFbeta1 induced a similar nuclear to cytoplasmic distribution of AR in primary cultures of rat prostate stromal cells. TGFbeta1, however, had no effect on AR distribution in either the LNCaP prostatic carcinoma cell line or the DDT1MF-2 leiomyosarcoma cell line. Specific cross-talk between TGFbeta1 and AR signaling pathways in prostate stromal cells may play a significant role in prostate development and stromal cell response in carcinoma progression.

Androgens↗

PubMed1998

Isoflurane reduces synaptic glutamate release without changing cytosolic free calcium in isolated nerve terminals.

The molecular mechanism of volatile anaesthetic action on presynaptic glutamate release is not clear. An inhibitory effect on voltage-gated calcium channels has been proposed. The present study examines the effect of isoflurane on cytosolic free calcium and synaptic glutamate release from isolated nerve terminals. Synaptosomes from rat cerebral cortex were used. Glutamate was measured with a continuous fluorometric measurement in a spectrophotometer as the fluorescence of NADPH and calcium as the fluorescence of fura-2. Isoflurane reduced the calcium-dependent glutamate release evoked by membrane depolarization with 4-aminopyridine in an inversely dose-dependent manner. The glutamate release was reduced by 56, 43 and 36% in response to isoflurane 0.5, 1.5 and 3.0%, respectively (for all: P < 0.05). Membrane depolarization evoked a rise in cytosolic free calcium of approximately 34%. Addition of isoflurane (0.5, 1.5 and 3.0%) produced no significant change in cytosolic free calcium. These results indicate that the isoflurane-induced reduction in presynaptic glutamate release is caused by other mechanisms than blocking voltage-gated calcium channels. As the release is inversely dose-dependent, two or more mechanisms could be involved.

4-Aminopyridine↗

PubMed1997

Effect of the nematode-trapping fungus Duddingtonia flagrans on the free-living stages of horse parasitic nematodes: a pilot study.

A plot experiment was conducted to investigate the ability of the nematode-trapping fungus Duddingtonia flagrans to reduce the transmission of infective horse strongyle larvae from deposited dung onto surrounding herbage. At three different times during the summer 1995, three groups of horses, naturally infected with large and small strongyles, were fed different doses of D. flagrans spores, while a fourth group of animals served as non-fungal controls. Faeces from all four groups of horses were deposited as artificial dung pats on a parasite-free pasture. Every second week for 8 weeks after dung deposition, a subsample of the herbage surrounding each dung pat was collected and the number of larvae on the grass determined. Also, the larval reduction capacity of the fungus was evaluated by faecal cultures set up from all groups of horses. The faecal cultures showed that a sufficient number of spores of D. flagrans survived passage through the horses alimentary tract to significantly reduce the number of developing larvae. A lower reduction of larval numbers was observed when a different batch of fungal material was used at the beginning of the season. Dry climatic conditions affected the transmission of infective larvae in all groups, resulting in low numbers of larvae on the herbage. During the rainy periods a significant reduction in the number of larvae recovered was observed around all fungal containing pats. There were no significant differences between the number of fungal spores and the level of reduction caused by the fungus.

Animal Feed↗

PubMed1997

Permeability of the blood-retinal barrier in healthy humans. European Concerted Action on Ocular Fluorometry.

BACKGROUND: The aim of this study was to compare the inward permeability of the blood-retinal barrier in healthy subjects from six European cities. METHODS: Seventy-two healthy subjects (age 20-70 years) were selected. At 30 min and 60 min after fluorescein injection, fluorescein mass in vitreous was calculated from the concentrations measured along the optical axis of the eye. Non-protein-bound fluorescein (NPBF) concentrations were measured in plasma prepared from blood samples taken 7, 15 and 55 min after injection. Blood-retinal barrier permeability (PBRB) was calculated from the vitreous fluorescein mass and the time integral of NPBF and was corrected for the autofluorescence of ocular tissue and for lenticular light transmittance. RESULTS: Mean PBRB values +/- SD (nm.s-1) were 2.07 +/- 0.54 (Coimbra), 2.01 +/- 0.43 (Frankfurt), 2.24 +/- 0.50 (Ghent), 2.37 +/- 0.56 (Herlev), 1.89 +/- 0.44 (Leiden) and 1.74 +/- 0.38 (Porto). Differences between centers were not significant (P > 0.35). Measurements were reproducible and independent of the time after fluorescein injection (P > 0.50). A PBRB higher than 3.16 nm.s-1 or a value which had increased by 32% was considered abnormal (P < 0.05). CONCLUSION: PBRB values were similar in all centers. The results demonstrate that this is a highly sensitive and reliable method for measuring the permeability of the blood-retinal barrier.

Adult↗

PubMed1997

Efflux of gamma-aminobutyric acid caused by changes in ion concentrations and cell swelling simulating the effect of cerebral ischaemia.

The relationships among ischaemic GABA efflux from brain tissue and extracellular and intracellular concentrations of sodium, chloride and potassium ions were investigated by means of 1) transverse hippocampal slices from rat and 2) functional expression of a high affinity GABA transporter in Xenopus oocytes. Brain slices were incubated for 20 min in medium where extracellular sodium and chloride were substituted with impermeant ions. Isethionate (Iseth) substitution for chloride generated a 7-fold increase in GABA efflux. Choline (Chol) but not N-methyl-D-glucamine (NMDG) substitution for sodium likewise increased GABA efflux. Reducing the osmolarity of the medium by decreasing both sodium and chloride concentrations (Hyp) increased GABA efflux 3-fold. This release was blocked by mannitol (Man). Blocking sodium channels with 1 microM of tetrodotoxin (TTX) also increased the release 3-fold. Energy deprivation (ED) increased the GABA release 50-fold. ED/Iseth left the release unchanged, ED/Chol increased the GABA efflux by 23%, whereas ED/NMDG reduced the release by 41%. Adding mannitol did not block the ED-evoked release, whereas TTX reduced it by 52%. Release of preloaded [3H]-GABA from oocytes expressing the GAT-1 GABA transporter was then examined. Depolarisation by current injection or 100 mM extracellular K+ did not increase GABA release. Sodium chloride injection, however, caused membrane depolarisation and a 100-fold increased GABA efflux from the oocytes. This release was blocked when the osmolarity was increased extracellularly by adding mannitol. These results show that 1) TTX releases GABA from brain tissue but blocks release during ED, 2) the high affinity GABA carrier must be altered in order to reverse, 3) ischaemic GABA release is sodium independent, and is modulated by large cations, 4) mannitol blocks the reversal of high affinity carriers in oocytes, but the release from brain slices during ED is unaffected. Taken together, the results suggest that ischaemic release of GABA from brain tissue does not occur by means of reversed high affinity carriers alone, but rather that it is controlled by more complex mechanisms.

Animals↗

PubMed1997

Microbial linear plasmids.

While plasmids were originally considered to be generally circular until almost two decades ago, linear elements were reported to exist as well. They are now known to be common genetic elements in both, pro- and eukaryotes. Two types of linear plasmids exist, the so-called hairpin plasmids with covalently closed ends and those with proteins bound to their 5' termini. Hairpin plasmids are common in human-pathogenic Borrelia spirochetes, in which they are instrumental in escape from the immunological response; cryptic hairpin elements are present in mitochondria of the plant pathogenic fungus Rhizoctonia solani. Plasmids with 5' attached proteins constitute the largest group. In actinomycetous bacteria they are conjugative and usually confer advantageous phenotypes, e.g. formation of antibiotics, degradation of xenobiotics, heavy-metal resistance and growth on hydrogen as the sole energy source. In contrast, the majority of linear plasmids from eukaryotes are cryptic, with only a few exceptions. In some yeasts a killer phenotype may be associated, the most thoroughly investigated elements being those from Kluyveromyces lactis killer strains. In Neurospora spp. and in Podospora anserina, senescence and longevity respectively are correlated with linear plasmids. This review focuses on the biology of linear plasmids, their environmental significance and their use as tools in molecular and applied microbiology.

Bacteria↗

PubMed1997

The preventive effect of the fungus Duddingtonia flagrans on trichostrongyle infections of lambs on pasture.

Four groups of 8 parasite-naive Dorset-crossbred lambs, 3-4 months old, were turned out on infected pasture on 2 May and allocated to 4 separate paddocks. From May to September, 2 groups received Duddingtonia flagrans (10(6) chlamydospores per kg body weight per lamb per day) mixed in 100 g of barley, while the other 2 groups received barley only. All groups remained set-stocked until slaughter for worm counts on 10 October. In late June, all lambs were treated with fenbendazole due to severe parasitic gastroenteritis in all groups. The faecal egg counts were comparable for the 2 treatments throughout the grazing period. Larval development of Ostertagia/Trichostrongylus spp. in faecal cultures was 1-28% in the fungi-fed groups compared with 60-80% in the untreated groups (P < 0.05). In September, pasture larval counts of Ostertagia/Trichostrongylus were 930 and 4400 L3 kg-1 on paddocks of fungi-fed and untreated groups, respectively. Corresponding figures for Nematodirus spp. were 7200 and 11600 L3 kg-1, respectively. At slaughter, the number of immature Ostertagia spp. was 62% lower in the fungi-fed groups compared with the untreated groups (P < 0.05). Four parasite-free lambs were introduced to each paddock during the period 3-23 October and slaughtered for worm counts after 3 weeks of housing. The total worm burden of tracers on paddocks previously grazed by fungi-fed lambs was reduced 86% (P < 0.05; geometric means) compared with control groups, while significant reductions were also seen in abomasal worm counts (68%; P < 0.05), N. spathiger (98%; P < 0.05) and for N. battus (97%; P < 0.01). It is concluded that dosing sheep with D. flagrans while grazing may limit the build up of pasture contamination in the late grazing season and subsequently limit the intake of larvae in sheep.

Animals↗