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Biomedical subjects

J Larsen

Publications and source records attributed to J Larsen.

At least 55 records · Page 3Linked to original sources
PubMed1999

Generalizable patterns in neuroimaging: how many principal components?

Generalization can be defined quantitatively and can be used to assess the performance of principal component analysis (PCA). The generalizability of PCA depends on the number of principal components retained in the analysis. We provide analytic and test set estimates of generalization. We show how the generalization error can be used to select the number of principal components in two analyses of functional magnetic resonance imaging activation sets.

Algorithms↗
PubMed1999

Suppression of the biocontrol agent trichoderma harzianum by mycelium of the arbuscular mycorrhizal fungus glomus intraradices in root-free soil

Trichoderma harzianum is an effective biocontrol agent against several fungal soilborne plant pathogens. However, possible adverse effects of this fungus on arbuscular mycorrhizal fungi might be a drawback in its use in plant protection. The objective of the present work was to examine the interaction between Glomus intraradices and T. harzianum in soil. The use of a compartmented growth system with root-free soil compartments enabled us to study fungal interactions without the interfering effects of roots. Growth of the fungi was monitored by measuring hyphal length and population densities, while specific fatty acid signatures were used as indicators of living fungal biomass. Hyphal 33P transport and beta-glucuronidase (GUS) activity were used to monitor activity of G. intraradices and a GUS-transformed strain of T. harzianum, respectively. As growth and metabolism of T. harzianum are requirements for antagonism, the impact of wheat bran, added as an organic nutrient source for T. harzianum, was investigated. The presence of T. harzianum in root-free soil reduced root colonization by G. intraradices. The external hyphal length density of G. intraradices was reduced by the presence of T. harzianum in combination with wheat bran, but the living hyphal biomass, measured as the content of a membrane fatty acid, was not reduced. Hyphal 33P transport by G. intraradices also was not affected by T. harzianum. This suggests that T. harzianum exploited the dead mycelium but not the living biomass of G. intraradices. The presence of external mycelium of G. intraradices suppressed T. harzianum population development and GUS activity. Stimulation of the hyphal biomass of G. intraradices by organic amendment suggests that nutrient competition is a likely means of interaction. In conclusion, it seemed that growth of and phosphorus uptake by the external mycelium of G. intraradices were not affected by the antagonistic fungus T. harzianum; in contrast, T. harzianum was adversely affected by G. intraradices.

Journal Article↗
PubMed1999

Improved sensitivity in comparative genomic hybridization analysis of DNA heteroploid cell mixtures after pre-enrichment of subpopulations by fluorescence activated cell sorting.

Cytogenetic analysis of solid tumors with comparative genomic hybridization (CGH) is hampered by the dilution of DNA from individual tumor subpopulations with DNA from other cells. We investigated to what extent this dilution effect can be alleviated using fluorescence activated cell sorting (flow sorting) of experimental DNA heteroploid cell mixtures prior to CGH. From mixtures of normal lymphocytes with triploid K-562 cells the individual components were sorted according to stemline DNA content and processed by CGH in comparison with pure K-562 samples and the original mixtures. Compared with 30 autosome copy number imbalances found in pure K-562 samples, a mixture with 32% K-562 cells showed 16 imbalances, and none were detected in mixtures with 13% or 5% K-562 cells. In contrast, 29, 22 and 23 imbalances were detected in K-562 nuclei sorted from the 32%, 13% and 5% mixtures, respectively. This indicate that CGH analysis of flow sorted DNA aneuploid subpopulations enables a specific cytogenetic analysis of the individual subclones in a DNA heteroploid cell population.

Cell Separation↗
PubMed1998

Potent and selective non-cysteine-containing inhibitors of protein farnesyltransferase.

Potent and selective non-thiol-containing inhibitors of protein farnesyltransferase are described. FTI-276 (1) was transformed into pyridyl ether analogue 19. The potency of pyridyl ether 19 was improved by modification of the biphenyl core to that of an o-tolyl substituted biphenyl core to give 29. In addition to 0.4 nM in vitro potency, 29 displayed 350 nM potency in whole cells as the parent carboxylic acid. The o-tolyl biphenyl core dramatically and unexpectedly enhanced the potency of other compounds as exemplified by 46, 47, 48, and 49.

3T3 Cells↗
PubMed1998

[Antabus treatment in general practice. A pharmaco-epidemiological study of prescription patterns based on a prescription database].

Denmark has a long tradition for the use of alcohol-aversive drugs in the treatment of alcoholism, most commonly disulfiram (Antabuse). The purpose of this study was to examine the prescription patterns for disulfiram in Danish general practice on an individual level. By means of a prescription database we analysed 150,787 prescriptions on reimbursed medicine to persons who had redeemed prescriptions for alcohol-aversive drugs during the period 1.1.1993 to 31.12.1995 in the County of Funen. Prevalence of disulfiram treatment was 12 per 10,000 inhabitants, three-year prevalence 75 per 10,000 inhabitants and incidence 21 per 10,000 inhabitants per year. Eighty-seven percent of treatments were stopped at (or before) the expiration of one prescription, and relapse was frequent (46%).

Adult↗
PubMed1998

Anti-insulin antibodies may cause hypoglycaemia following pancreas transplantation.

Some pancreas transplantation (PTX) recipients experience hypoglycaemia after transplant. We studied the incidence and pattern of hypoglycaemic symptoms following PTX and later studied the glucose and pancreatic hormone response to Sustacal in patients with and without hypoglycaemia following PTX. In a survey of 54 PTX recipients who were 2 to 33 months post-transplant, 29 reported symptoms of hypoglycaemia at any time following their transplant. Of 12 patients who tried to document their blood glucose during any episode, 5 had a blood glucose less than 3.3 mmol/l, and another 5 documented a blood glucose from between 3.33 and 3.88 mmol/l. The patients reporting symptoms were less likely to be insulin resistant with longer time post-PTX, lower body mass index (BMI), and on lower doses of prednisone. Later, 12 patients with established, repeated episodes of hypoglycaemia following PTX were case-matched to PTX recipients without hypoglycaemic symptoms. Fasting glucose, free and total immunoreactive insulin (IRI), C-peptide, proinsulin and glucagon were measured following a 4 h Sustacal challenge. The hypoglycaemic group was further divided into those whose glucose rose after Sustacal (Hypo-High) and those whose blood glucose did not rise from baseline concentration (Hypo-Flat). The Hypo-High subgroup had a lower fasting free/total IRI ratio in addition to a greater increase in blood glucose after Sustacal compared with either Hypo-Flat or non-hypoglycaemic transplant recipients. The low free/total insulin ratio and hyperglycaemic response to Sustacal are consistent with the presence of anti-insulin antibodies, an established cause of hypoglycaemia. In summary, documented hypoglycaemia, while uncommon, may occur and be significant following PTX. Anti-insulin antibodies may be one of the many factors contributing to hypoglycaemia in this population.

Adult↗
PubMed1998

Prosthesis evaluation questionnaire for persons with lower limb amputations: assessing prosthesis-related quality of life.

OBJECTIVE: To develop a self-report questionnaire for persons with lower limb amputations who use a prosthesis. The resulting scales were intended to be suitable to evaluate the prosthesis and life with the prosthesis. The conceptual framework was health-related quality of life. DESIGN: Multiple steps of scale development, terminating with test-retest of the Prosthesis Evaluation Questionnaire (PEQ) by mail. SOURCE OF SAMPLE: Records from two Seattle hospitals. PATIENTS: Ninety-two patients with lower limb amputations who varied by age, reason for amputation, years since amputation, and amputation level. MAIN OUTCOME MEASURES: The 10 scales used were 4 prosthesis function scales (Usefulness, Residual Limb Health, Appearance, and Sounds), 2 mobility scales (Ambulation and Transfers), 3 psychosocial scales (Perceived Responses, Frustration, and Social Burden), and 1 Well-being scale. Validation measures were the Medical Outcomes Study Short Form-36, the Social Interaction subscale from the Sickness Impact Profile, and the Profile of Mood States-short form. RESULTS: Nine PEQ scales demonstrated high internal consistency. All met test-retest criteria for comparing group results. Validity was described based on methods used to gather original items, distribution of scores, and comparison of scores with criterion variables. CONCLUSIONS: The PEQ scales displayed good psychometric properties. Future work will assess responsiveness of PEQ scales to changes in prosthetic components. We conclude that they will be useful in evaluation of prosthetic care.

Activities of Daily Living↗
PubMed1998

Chlamydial elementary bodies are translocated on the surface of epithelial cells.

Infection of eukaryotic cells by intracellular pathogens such as chlamydia requires attachment to the host cell surface. Chlamydia are thought to attach to the tips of microvilli in confluent monolayers of polarized cells. In vitro evidence obtained from migrating epithelial cells suggested that during healing the route of pathogen uptake might be different from that in intact epithelia. The small size of infectious chlamydial elementary bodies (approximately 0.3 microm in diameter) has made it difficult, however, to analyze the early stages of pathogen-host cell interaction in living cells by conventional microscopy. Contrast-enhanced video microscopy was therefore used to examine the earliest events of host-pathogen interaction and test the hypothesis that chlamydial uptake into the healing epithelia can involve translocation over the host cell surface. Observations made in this way were validated by scanning and immunofluorescence microscopy. These studies revealed two fates for chlamydiae taken onto the lamellipodial surface: 1) some chlamydiae were moved in a random fashion on the cell surface or were detached into the culture medium, whereas 2) other chlamydiae were translocated across the lamellipodium in a highly directed manner toward the microvillous perinuclear region. After internalization, these latter chlamydiae were found within intracellular inclusions, which demonstrated that this route of attachment and location of uptake resulted in productive growth.

Bacterial Adhesion↗
PubMed1997

Progress in an ecotoxicological standard protocol with protozoa: results from a pilot ring test with Tetrahymena pyriformis.

The aim of this project was to develop a standardized multigeneration growth inhibition test protocol to assess the sublethal effects of industrial chemicals and pesticides on protozoans. The inclusion of a test with protozoa would be an ecologically relevant supplement to the existing basic set in aquatic toxicity testing. The different aspects evaluated in the pilot ring study include: two media, two volumes, two end points and two different methods to measure the cell density. Taking into account the aim to develop a simple, sensitive, reproducible and cost effective test, recommendations are made for a standardized protocol.

1-Octanol↗
PubMed1997

Acute colitis in adult horses. A review with emphasis on aetiology and pathogenesis.

This review article describes the different aetiological agents known or suspected to cause colitis in the adult horse, namely Salmonella spp., Clostridium spp., Ehrlichia risticii, Cyathostomes, fungi, various antibiotics, drugs, and toxins, with emphasis on their mechanism of action. For each of the infectious agents, diagnostic procedures are indicated. The effects of endotoxin can be important in all forms of equine colitis.

Acute Disease↗
PubMed1997

Limits for the use of forehead flaps for small and extensive midface reconstructions including septum/columella reconstructions.

I describe six selected cases of challenging reconstructions in the midface including a small deepithelialised and tunnelled flap for volume-replacement and conjunctiva-reconstruction in the orbit and a case of septum/columella reconstruction with a tunnelled paramedian forehead flap. Big flaps for extensive complex reconstructions in the midface (cheek, lip, and nose) emphasis the efficiency of the flaps. In extensive reconstructions the paramedian forehead might primarily be used for lining. Indian forehead flaps should be dissected to the base in the upper eyelid to increase their strength and for greater versatility. The base can be de-epithelialised without threatening its viability. This procedure allows the flap to be tunnelled and increases the mobility of the flap. Long flaps can even be folded without delay.

Aged↗
PubMed1997

DNA ploidy analysis in breast carcinoma. Comparison of unfixed and fixed tissue analyzed by image and flow cytometry.

OBJECTIVE: To form a methodologic basis for DNA analysis of ductal carcinoma in situ (DCIS) and invasive carcinoma (IC) of the breast, including very small lesions, by comparison of flow cytometric (FCM) and image cytometric (ICM) methods for DNA quantitation. STUDY DESIGN: The material consisted of 41 DCIS lesions and 26 ICs. FCM DNA analysis of unfixed, frozen samples were compared to (1) FCM of formalin-fixed, paraffin-embedded tissue; (2) ICM of imprints; and (3) ICM of paraffin-embedded tissue sections. RESULTS: FCM of unfixed tissue showed higher DNA measurement precision and a higher number of DNA nondiploid clones as compared to the other three methods. For the classification of DNA diploid/nondiploid cases, high concordance rates were found between the methods. Discordant cases were predominantly DNA neardiploid by FCM of unfixed tissue but DNA diploid by the other methods. The reproducibility of the DNA index (DI) was best in the interval 1.2 < DI < or = 2.2; it was 74% for FCM of fixed tissue and 79% for ICM of imprints. Clones with DI > 3 were found almost exclusively by ICM of imprints. For ICM of tissue sections, DI could not be reliably estimated. By ICM, contrary to FCM, a combined DNA diploid and nondiploid pattern was found frequently. CONCLUSION: Each of the methods has its own advantages and limitations. If possible, FCM should be combined with ICM. FCM of unfixed tissue is superior to the other methods with respect to precise DI estimation. Alternatively, FCM of fixed tissue and ICM of imprints may both give a reliable estimate of DI. ICM of tissue sections can discriminate DNA diploid from nondiploid clones, except for neardiploid subpopulations, and permits the analysis of very small lesions.

Breast Neoplasms↗
PubMed1996

An analysis of dimethylsulfoxide-induced action potential block: a comparative study of DMSO and other aliphatic water soluble solutes.

A series of water soluble aliphatic solutes were chosen for study. Fifty percent effective doses (ED50) to block propagated compound action potentials (AP's) were obtained by examining dose-response relations for each solute. All solutes used were liquids at room temperature and are typically used as solvents. The solutes studied were dimethylsulfoxide (DMSO), dimethylformamide (DMF), dimethylacetamide, acetone, and hexamethylphosphoramide (HMPA); the octanol/water partition coefficients for these test substances form an ordered sequence that increased 40-fold from DMSO to HMPA. AP's were recorded from desheathed frog sciatic nerves using the sucrose-gap technique; test solutes were added to Ringer's solution and applied externally to the nerve. ED50's for the solutes could be predicted as a function of the molar volume (dV/dn), polarity (P), and the hydrogen bond acceptor basicity (beta). Voltage-clamp experiments employing the vaseline-gap technique on single muscle fibers showed that each solute reduced Na+ current with little change in their kinetics at all voltages studied. Experiments using DMSO or DMF showed that Na+ channel block alone is insufficient to explain the respective ED50 values of AP block. Experiments conducted using a chloride transport-sensitive membrane fluidity assay, using rat pancreas secretory granules, suggested that each of the solutes act to increase membrane fluidity at doses below and above ED50 values. Light microscopic observations of fixed thick sections of whole nerves previously exposed to DMSO or DMF show structural changes; however, ED50 values cannot be simply explained by osmotic alterations of nerve structure. ED50's are likely to be produced by a combination of effects including osmotically induced nerve structural changes, ion channel block, and fluidity changes. The toxicity (lethal doses or toxic concentrations) of each of these five solutes correlates well with the ED50 and could be predicted as a function of dV/dn, P, and beta.

Acetamides↗
PubMed1996

Adaptive changes in the acute haemodynamic effects of cilazapril during chronic treatment. Comparison with long-term clinical effect.

OBJECTIVE: To study the adaptive changes in the acute haemodynamic response to ACE inhibition during chronic treatment in CHF. METHODS: The acute and chronic effects of oral cilazapril (CLZ) treatment, an ACE-inhibitor with prolonged duration on haemodynamic measures (PCWP, PAP, RAP, CI and SVR) and clinical parameters (Quality-of-Life and NYHA class) were investigated in a double-blind, randomised, placebo-controlled trial in CHF. One hundred and thirty five patients (112 completing) in NYHA Classes II-III, on digitalis and diuretic treatment, were randomised after 2 weeks of placebo run-in, to receive either placebo or CLZ 0.5 mg, 1.0 mg or 2.5 mg daily for 12 weeks, followed by 2 week placebo wash-out. Haemodynamic studies, including exercise tests before and 3 h after medication, were performed on the first and last days of treatment. Measurements were performed at rest and at the maximum exercise level. RESULTS: In ACEI-naive patients oral CLZ 0.5 and 1 mg/d caused a dose dependent decrease in PCWP and diastolic PAP, and a significant reduction of SVR mg. A slight increase in CI was observed in all groups. The maximum effect was observed 3-5 h post dose. After 12 weeks of oral treatment, the acute response was similar but was attenuated relative to the first dose. Exercise tolerance improved in a dose dependent manner. The NYHA classification remained unchanged or improved in the majority of patients. Entry into the 2.5 mg group had to be terminated at an early stage due to severe adverse events observed after the first dose. CONCLUSION: During chronic treatment, the haemodynamic response to oral cilazapril was attenuated, indicating that continued clinical improvement in patients with CHF on CLZ is independent of to its acute haemodynamic effects.

Adult↗