Showing papers by "Lund University published in 1999"

Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide

Abstract: The endogenous cannabinoid receptor agonist anandamide is a powerful vasodilator of isolated vascular preparations, but its mechanism of action is unclear. Here we show that the vasodilator response to anandamide in isolated arteries is capsaicin-sensitive and accompanied by release of calcitonin-gene-related peptide (CGRP). The selective CGRP-receptor antagonist 8-37 CGRP, but not the cannabinoid CB1 receptor blocker SR141716A, inhibited the vasodilator effect of anandamide. Other endogenous (2-arachidonylglycerol, palmitylethanolamide) and synthetic (HU 210, WIN 55,212-2, CP 55,940) CB1 and CB2 receptor agonists could not mimic the action of anandamide. The selective 'vanilloid receptor' antagonist capsazepine inhibited anandamide-induced vasodilation and release of CGRP. In patch-clamp experiments on cells expressing the cloned vanilloid receptor (VR1), anandamide induced a capsazepine-sensitive current in whole cells and isolated membrane patches. Our results indicate that anandamide induces vasodilation by activating vanilloid receptors on perivascular sensory nerves and causing release of CGRP. The vanilloid receptor may thus be another molecular target for endogenous anandamide, besides cannabinoid receptors, in the nervous and cardiovascular systems.

Time-varying periodic convolutional codes with low-density parity-check matrix

Abstract: We present a class of convolutional codes defined by a low-density parity-check matrix and an iterative algorithm for decoding these codes The performance of this decoding is close to the performance of turbo decoding Our simulation shows that for the rate R=1/2 binary codes, the performance is substantially better than for ordinary convolutional codes with the same decoding complexity per information bit As an example, we constructed convolutional codes with memory M=1025, 2049, and 4097 showing that we are about 1 dB from the capacity limit at a bit-error rate (BER) of 10/sup -5/ and a decoding complexity of the same magnitude as a Viterbi decoder for codes having memory M=10

Histopathology of common tendinopathies. Update and implications for clinical management.

Abstract: Tendon disorders are a major problem for participants in competitive and recreational sports. To try to determine whether the histopathology underlying these conditions explains why they often prove recalcitrant to treatment, we reviewed studies of the histopathology of sports-related, symptomatic Achilles, patellar, extensor carpi radialis brevis and rotator cuff tendons. The literature indicates that healthy tendons appear glistening white to the naked eye and microscopy reveals a hierarchical arrangement of tightly packed, parallel bundles of collagen fibres that have a characteristic reflectivity under polarised light. Stainable ground substance (extracellular matrix) is absent and vasculature is inconspicuous. Tenocytes are generally inconspicuous and fibroblasts and myofibroblasts absent. In stark contrast, symptomatic tendons in athletes appear grey and amorphous to the naked eye and microscopy reveals discontinuous and disorganised collagen fibres that lack reflectivity under polarised light. This is associated with an increase in the amount of mucoid ground substance, which is confirmed with Alcian blue stain. At sites of maximal mucoid change, tenocytes, when present, are plump and chondroid in appearance (exaggerated fibrocartilaginous metaplasia). These changes are accompanied by the increasingly conspicuous presence of cells within the tendon tissue, most of which have a fibroblastic or myofibroblastic appearance (smooth muscle actin is demonstrated using an avidin biotin technique). Maximal cellular proliferation is accompanied by prominent capillary proliferation and a tendency for discontinuity of collagen fibres in this area. Often, there is an abrupt discontinuity of both vascular and myofibroblastic proliferation immediately adjacent to the area of greatest abnormality. The most significant feature is the absence of inflammatory cells. These observations confirm that the histopathological findings in athletes with overuse tendinopathies are consistent with those in tendinosis--a degenerative condition of unknown aetiology. This may have implications for the prognosis and timing of a return to sport after experiencing tendon symptoms. As the common overuse tendon conditions are rarely, if ever, caused by 'tendinitis', we suggest the term 'tendinopathy' be used to describe the common overuse tendon conditions. We conclude that effective treatment of athletes with tendinopathies must target the most common underlying histopathology, tendinosis, a noninflammatory condition.

Good genes, oxidative stress and condition-dependent sexual signals

Abstract: The immune and the detoxication systems of animals are characterized by allelic polymorphisms, which underlie individual differences in ability to combat assaults from pathogens and toxic compounds. Previous studies have shown that females may improve offspring survival by selecting mates on the basis of sexual ornaments and signals that honestly reveal health. In many cases the expression of these ornaments appears to be particularly sensitive to oxidative stress. Activated immune and detoxication systems often generate oxidative stress by an extensive production of reactive metabolites and free radicals. Given that tolerance or resistance to toxic compounds and pathogens can be inherited, female choice should promote the evolution of male ornaments that reliably reveal the status of the bearers' level of oxidative stress. Hence, oxidative stress may be one important agent linking the expression of sexual ornaments to genetic variation in fitness-related traits, thus promoting the evolution of female mate choice and male sexual ornamentation, a controversial issue in evolutionary biology ever since Darwin.

Piecewise quadratic stability of fuzzy systems

Abstract: Presents an approach to stability analysis of fuzzy systems. The analysis is based on Lyapunov functions that are continuous and piecewise quadratic. The approach exploits the gain-scheduling nature of fuzzy systems and results in stability conditions that can be verified via convex optimization over linear matrix inequalities. Examples demonstrate the many improvements over analysis based on a single quadratic Lyapunov function. Special attention is given to the computational aspects of the approach and several methods to improve the computational efficiency are described.

Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD).

Abstract: In 1992 the Core Assessment Program for Intracerebral Transplantations (CAPIT) was published providing the minimal requirements for a common patient evaluation protocol. Despite the intent, the program was thought to be too laborious to carry out in large scale trials, and it also lacked evaluations of cognitive functions and quality of life. Moreover, the CAPIT was designed for neural transplantation only and has not been revised since. Since then, pallidotomy and deep brain stimulation have emerged as additional treatment modalities but there exists no common tool for evaluation of, and between, the techniques. In 1996, within the framework of NECTAR (Network for European CNS Transplantation and Restoration), a dedicated program entitled "Neurosurgical Interventions in Parkinson's Disease" (NIPD) was funded by the European Union Biomed 2 program to develop a new Core Assessment Program for Surgical Interventional Therapies in PD (CAPSIT-PD) and to establish an European registry for patients with PD subjected to functional neurosurgery. This article presents the recommendations of this new program.

Fundamentals of Convolutional Coding

Abstract: From the Publisher: Convolutional codes, among the main error control codes, are routinely used in applications for mobile telephony, satellite communications, and voice-band modems. Written by two leading authorities in coding and information theory, this book brings you a clear and comprehensive discussion of the basic principles underlying convolutional coding. This book can be used as a textbook for graduate-level electrical engineering students. It will be of key interest to researchers and engineers of wireless and mobile communication, satellite communication, and data communication.

Quality of Life in Head and Neck Cancer Patients: Validation of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-H&N35

Abstract: PURPOSE: The aim of this study was to define the scales and test the validity, reliability, and sensitivity of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-H&N35, a questionnaire designed to assess the quality of life of head and neck (H&N) cancer patients in conjunction with the general cancer-specific EORTC QLQ-C30. PATIENTS AND METHODS: Questionnaires were given to 500 H&N cancer patients from Norway, Sweden, and the Netherlands as part of two prospective studies. The patients completed the questionnaires before, during (Norway and Sweden only), and after treatment, yielding a total of 2070 completed questionnaires. RESULTS: The compliance rate was high, and the questionnaires were well accepted by the patients. Seven scales were constructed (pain, swallowing, senses, speech, social eating, social contact, sexuality). Scales and single items were sensitive to differences between patient subgroups with relation to site, stage, or performance st...

Vascular Endothelial Growth Factor Has Neurotrophic Activity and Stimulates Axonal Outgrowth, Enhancing Cell Survival and Schwann Cell Proliferation in the Peripheral Nervous System

Abstract: Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells, and it promotes angiogenesis in vivo. Here we report that VEGF(165) has neurotrophic actions on cultured adult mouse superior cervical ganglia (SCG) and dorsal root ganglia (DRG), measured as axonal outgrowth. Maximal effect was observed at 10-50 ng/ml for SCG and 100 ng/ml for DRG. VEGF-induced axonal outgrowth was inhibited by the mitogen-activated protein kinase kinase inhibitor PD 98059 but not by the protein kinase inhibitor K252a. VEGF also increased survival of both neurons and satellite cells and the number of proliferating Schwann cells. Immunocytochemistry and immunoblotting revealed that VEGF was expressed in virtually all nerve cells in the SCG but only in a population of small-diameter (<35 micrometers) neurons representing approximately 30% of the neurons in DRG. Immunostaining showed that the VEGF receptor fetal liver kinase receptor (flk-1) was found on nerve cell bodies in DRG and to a lesser extent on neurons in SCG. Growth cones of regenerating axons from both types of ganglia exhibited flk-1 immunoreactivity, as did Schwann cells. We conclude that VEGF has both neurotrophic and mitogenic activity on cells in the peripheral nervous system.

Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient

Abstract: Synaptic dopamine release from embryonic nigral transplants has been monitored in the striatum of a patient with Parkinson's disease using [11C]-raclopride positron emission tomography to measure dopamine D2 receptor occupancy by the endogenous transmitter. In this patient, who had received a transplant in the right putamen 10 years earlier, grafts had restored both basal and drug-induced dopamine release to normal levels. This was associated with sustained, marked clinical benefit and normalized levels of dopamine storage in the grafted putamen. Despite an ongoing disease process, grafted neurons can thus continue for a decade to store and release dopamine and give rise to substantial symptomatic relief.

Perlecan Maintains the Integrity of Cartilage and Some Basement Membranes

Abstract: Perlecan is a heparan sulfate proteoglycan that is expressed in all basement membranes (BMs), in cartilage, and several other mesenchymal tissues during development. Perlecan binds growth factors and interacts with various extracellular matrix proteins and cell adhesion molecules. Homozygous mice with a null mutation in the perlecan gene exhibit normal formation of BMs. However, BMs deteriorate in regions with increased mechanical stress such as the contracting myocardium and the expanding brain vesicles showing that perlecan is crucial for maintaining BM integrity. As a consequence, small clefts are formed in the cardiac muscle leading to blood leakage into the pericardial cavity and an arrest of heart function. The defects in the BM separating the brain from the adjacent mesenchyme caused invasion of brain tissue into the overlaying ectoderm leading to abnormal expansion of neuroepithelium, neuronal ectopias, and exencephaly. Finally, homozygotes developed a severe defect in cartilage, a tissue that lacks BMs. The chondrodysplasia is characterized by a reduction of the fibrillar collagen network, shortened collagen fibers, and elevated expression of cartilage extracellular matrix genes, suggesting that perlecan protects cartilage extracellular matrix from degradation.

Photosynthetic control of chloroplast gene expression

Abstract: Redox chemistry—the transfer of electrons or hydrogen atoms—is central to energy conversion in respiration and photosynthesis. In photosynthesis in chloroplasts, two separate, light-driven reactions, termed photosystem I and photosystem II, are connected in series by a chain of electron carriers1,2,3. The redox state of one connecting electron carrier, plastoquinone, governs the distribution of absorbed light energy between photosystems I and II by controlling the phosphorylation of a mobile, light-harvesting, pigment–protein complex4,5. Here we show that the redox state of plastoquinone also controls the rate of transcription of genes encoding reaction-centre apoproteins of photosystem I and photosystem II. As a result of this control, the stoichiometry between the two photosystems changes in a way that counteracts the inefficiency produced when either photosystem limits the rate of the other. In eukaryotes, these reaction-centre proteins are encoded universally within the chloroplast. Photosynthetic control of chloroplast gene expression indicates an evolutionary explanation for this rule: the redox signal-transduction pathway can be short, the response rapid, and the control direct.

Site-Specific Migration and Neuronal Differentiation of Human Neural Progenitor Cells after Transplantation in the Adult Rat Brain

Abstract: Neural progenitor cells obtained from the embryonic human forebrain were expanded up to 107-fold in culture in the presence of epidermal growth factor, basic fibroblast growth factor, and leukemia inhibitory growth factor. When transplanted into neurogenic regions in the adult rat brain, the subventricular zone, and hippocampus, the in vitro propagated cells migrated specifically along the routes normally taken by the endogenous neuronal precursors: along the rostral migratory stream to the olfactory bulb and within the subgranular zone in the dentate gyrus, and exhibited site-specific neuronal differentiation in the granular and periglomerular layers of the bulb and in the dentate granular cell layer. The cells exhibited substantial migration also within the non-neurogenic region, the striatum, in a seemingly nondirected manner up to ∼1–1.5 mm from the graft core, and showed differentiation into both neuronal and glial phenotypes. Only cells with glial-like features migrated over longer distances within the mature striatum, whereas the cells expressing neuronal phenotypes remained close to the implantation site. The ability of the human neural progenitors to respond in vivo to guidance cues and signals that can direct their differentiation along multiple phenotypic pathways suggests that they can provide a powerful and virtually unlimited source of cells for experimental and clinical transplantation.

Restoration of an inbred adder population

Abstract: The negative effects of inbreeding on population size are well documented in captive animals1, but there is surprisingly little evidence that genetic factors cause a decline in wild populations2,3, apart from a reported correlation of low levels of genetic variability with a high incidence of malformed or stillborn offspring4. From the point of view of conservation strategies, it is not only the effect of genetic factors on population decline that needs to be considered, but also whether introducing novel genes can prevent or reverse such a decline. Here we show that the introduction of new genes into a severely inbred and isolated population of adders (Vipera berus) halted its precipitous decline towards extinction and expanded the population dramatically.

Prospects for new restorative and neuroprotective treatments in Parkinson's disease

Abstract: The degeneration of forebrain dopamine systems in Parkinson's disease has been an effective target for pharmaceutical research over the past four decades. However, although dopamine replacement may alleviate the symptoms of the disease, it does not halt the underlying neuronal degeneration. The past decade has seen major advances in identifying discrete genetic and molecular causes of parkinsonism and mapping the events involved in nigral cell death. This new understanding of the pathogenesis of the disease now offers novel prospects for therapy based on targeted neuroprotection of vulnerable neurons and effective strategies for their replacement.

Quantification of bias related to the extraction of DNA directly from soils.

Abstract: In recent years, several protocols based on the extraction of nucleic acids directly from the soil matrix after lysis treatment have been developed for the detection of microorganisms in soil. Extraction efficiency has often been evaluated based on the recovery of a specific gene sequence from an organism inoculated into the soil. The aim of the present investigation was to improve the extraction, purification, and quantification of DNA derived from as large a portion of the soil microbial community as possible, with special emphasis placed on obtaining DNA from gram-positive bacteria, which form structures that are difficult to disrupt. Furthermore, we wanted to identify and minimize the biases related to each step in the procedure. Six soils, covering a range of pHs, clay contents, and organic matter contents, were studied. Lysis was carried out by soil grinding, sonication, thermal shocks, and chemical treatments. DNA was extracted from the indigenous microflora as well as from inoculated bacterial cells, spores, and hyphae, and the quality and quantity of the DNA were determined by gel electrophoresis and dot blot hybridization. Lysis efficiency was also estimated by microscopy and viable cell counts. Grinding increased the extracellular DNA yield compared with the yield obtained without any lysis treatment, but none of the subsequent treatments clearly increased the DNA yield. Phage λ DNA was inoculated into the soils to mimic the fate of extracellular DNA. No more than 6% of this DNA could be recovered from the different soils. The clay content strongly influenced the recovery of DNA. The adsorption of DNA to clay particles decreased when the soil was pretreated with RNA in order to saturate the adsorption sites. We also investigated different purification techniques and optimized the PCR methods in order to develop a protocol based on hybridization of the PCR products and quantification by phosphorimaging.

Comparison of Different Methods for the Detoxification of Lignocellulose Hydrolyzates of Spruce

Abstract: This study describes different detoxification methods to improve both cell growth and ethanol production by Baker's yeast, Saccharomyces cerevisiae. A dilute-acid hydrolyzate of spruce was used for the all detoxification methods tested. The changes in the concentrations of fermentable sugars and three groups of inhibitory compounds—aliphatic acids, furan derivatives, and phenolic compounds—were determined and the fermentability of the detoxified hydrolyzate was assayed. The applied detoxification methods included: treatment with alkali (sodium hydroxide or calcium hydroxide); treatment with sulfite (0.1% [w/v] or 1% [w/v] at pH 5.5 or 10); evaporation of 10% or 90% of the initial volume; anion exchange (at pH 5.5 or 10); enzymatic detoxification with the phenoloxidase laccase; and detoxification with the filamentous fungus Trichoderma reesei. An ion exchange at pH 5.5 or 10, treatment with laccase, treatment with calcium hydroxide, and treatment with T. reesei were the most efficient detoxification methods. Evaporation of 10% of the initial volume and treatment with 0.1% sulfite were the least efficient detoxification methods. Treatment with laccase was the only detoxification method that specifically removed only one group of the inhibitors, namely phenolic compounds. Anion exchange at pH 10 was the most efficient method for removing all three major groups of inhibitory compounds; however, it also resulted in loss of fermentable sugars.

Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies.

Abstract: The aim of the study was 1) to establish the prevalence of GAD antibodies (GADab) in a population-based study of type 2 diabetes in western Finland, 2) to genetically and phenotypically characterize this subgroup, and 3) to provide a definition for latent autoimmune diabetes in adults (LADA). The prevalence of GADab was 9.3% among 1,122 type 2 diabetic patients, 3.6% among 558 impaired glucose tolerance (IGT) subjects, and 4.4% among 383 nondiabetic control subjects. Islet antigen 2 antibodies (IA2ab) or islet cell antibodies were detected in only 0.5% of the GADab- patients. The GADab+ patients had lower fasting C-peptide concentrations (median [interquartile range]: 0.46 [0.45] vs. 0.62 [0.44] nmol/l, P = 0.0002) and lower insulin response to oral glucose compared with GADab- patients. With respect to features of the metabolic syndrome, the GADab+ patients had lower systolic (140 [29.1] vs. 148 [26.0] mmHg, P = 0.009) and diastolic (79.2 [17.6] vs. 81.0 [13.1] mmHg, P = 0.030) blood pressure values, as well as lower triglyceride concentrations (1.40 [1.18] vs. 1.75 [1.25] mmol/l, P = 0.003). GADab+ men had a lower waist-to-hip ratio compared with GADab- patients. Compared with GADab- patients and control subjects, the GADab+ patients had an increased frequency HLA-DQB1*0201/0302 (13 vs. 4%; P = 0.002) and other genotypes containing the *0302 allele (22 vs. 12%; P = 0.010). However, the frequency of these high-risk genotypes was significantly lower in GADab+ type 2 patients than in type 1 diabetes of young or adult onset (0201/0302 or 0302/X: 36 vs. 66 vs. 64%, P 5 relative units) in patients older than 35 years at onset of type 2 diabetes.

A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection

Abstract: The immunogenetic basis of severe infections caused by bacille Calmette-Guerin vaccine and environmental mycobacteria in humans remains largely unknown. We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild-type IFNGR1 allele. There were 12 independent mutation events at a single mutation site, defining a small deletion hotspot. Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication. The mutant alleles encode cell-surface IFNgamma receptors that lack the intra-cytoplasmic domain, which, through a combination of impaired recycling, abrogated signalling and normal binding to IFNgamma exert a dominant-negative effect. We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria.

Microbial findings at failing implants.

Abstract: The aim of this study was to evaluate qualitative differences in the subgingival microbiota at titanium implants, ad modum Branemark, demonstrating clinical and radiographic signs of loss of supporting tissues (peri-implantitis) as compared to implants surrounded by healthy tissues. A total of 37 patients demonstrating 1 or more implants with bone loss > or = 3 threads, bleeding on probing and/or suppuration and 51 patients with clinically healthy mucosa and no bone loss were recruited for the study. In each patient subgingival bacterial samples were obtained using paper-points, and subjected to microbiological analysis by culture. The two types of clinical conditions showed distinct bacterial profiles. For implants with peri-implantitis putative periodontal pathogens, such as Porphyromonas gingivalis, Prevotella intermedia/Prevotella nigrescens and Actinobacillus actinomycetemcomitans, were found in 60% of the cases and microorganisms primarily not associated with periodontitis, such as Staphylococcus spp., enterics and Candida spp., were found in 55% of the peri-imaplant lesions. In contrast, implants surrounded by healthy tissue demonstrated a microbiota associated with periodontal health. The results indicate that the microbiota of the healthy peri-implant sulci is similar to that from corresponding conditions around teeth. However, in peri-implant areas staphylococci, enterics and yeasts were found almost as frequently as periopathogens indicating differences as compared to the microbiota around periodontitis affected teeth. A microbiological diagnosis may therefore be of guidance for the choice of antimicrobial treatment in patients with peri-implant infection.

A broad range of human papillomavirus types detected with a general PCR method suitable for analysis of cutaneous tumours and normal skin

Abstract: A pair of degenerate PCR primers (FAP59/64) was designed from two relatively conserved regions of the L1 open reading frame of most human papillomaviruses (HPV). The size of the generated amplicon was about 480 bp. PCR using these primers was found capable of amplifying DNA from 87% (65/75) of the HPV types tested, its sensitivity being 1-10 copies for HPV-5, -20 and -30 clones. HPV was found in 63% (5/8) of tumour samples and in 63% (5/8) of normal skin biopsies from patients with various cutaneous tumours. HPV-5, HPV-8, HPV-12, HPVvs20-4 and six putatively novel HPV types were identified. No correlation was found to exist between specific HPV and tumour types. Skin surface swab samples from one or more sites on three of four healthy volunteers were found to contain HPV, types 12 and 49 being identified, as well as eight novel HPV types, two of which were also found among the patients. In all, HPV was detected in 75% (9/12) of those tested, five HPV types and 12 novel candidate types being identified, and 37% (7/19) of HPV-positive samples were found to manifest more than one HPV type. All the HPV detected manifested high degrees of nucleotide sequence similarity with HPV types associated with skin lesions and epidermodysplasia verruciformis. The overall HPV finding in the skin samples was 50% (20/40) using the FAP primers as compared to 18% (7/40) using another PCR test designed for skin types. The results thus suggest the new method to be sensitive and generally applicable for detecting cutaneous HPV.

Infection-Derived Enterococcus faecalis Strains Are Enriched in esp, a Gene Encoding a Novel Surface Protein

Abstract: We report the identification of a new cell wall-associated protein of Enterococcus faecalis. Studies on the distribution of the gene encoding this novel surface protein, Esp, reveal a significant (P < 0.001) enrichment in infection-derived E. faecalis isolates. Interestingly, the esp gene was not identified in any of 34 clinical E. faecium isolates or in 4 other less pathogenic enterococcal species tested. Analysis of the structural gene among various E. faecalis isolates reveals the existence of alternate forms of expression of the Esp protein. The deduced primary structure of the Esp protein from strain MMH594, inferred to be 1,873 amino acids (aa) with a predicted mass of approximately 202 kDa, reveals a core region consisting of repeat units that make up 50% of the protein. Esp bears global organizational similarity to the Rib and C alpha proteins of group B streptococci. Identity among Esp, Rib, and C alpha proteins is strikingly localized to a stretch of 13 aa within repeats of similar length. The high degree of conservation of this 13-residue sequence suggests that it plays an important role in the natural selection for this trait among infection-derived E. faecalis and group B streptococcal isolates.