| 11. |
- Almroth, Gabriel, 1953-
(författare)
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Immunoglobulins, immunoglobulin subclass-distributions and serologic markers in some renal and systemic disorders
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this study we evaluated pathogenetic factors and possible mediators of renal and systemic disorders where immunologic mechanisms might be of importance.An abberant immunoglobulin and IgG-subclass distribution was detected in 103 patients with primary and secondary glomerulonephritis as well as in 38 patients with the systemic disease primary Sjögren 's syndrome or purpura hypergammaglobulinemica (elevated IgG1 and low IgG2 ).The drug hydralazine, an anti-hypertensive, was considered to cause renal disease on an immunologic base in 17 patients, with autoantibody production (mainly ANA and antibodies to myeloperoxidase).Dialysis-patients showed adequate antibody responses to vaccination against pneumococci but low responses against hepatitis B, while the IgG-subclass response of the hepatitis B antibody (anti-HBs) was low, but not shown to be significantly different from that of healthy adults.A therapeutical removal of igG-antibodies with immunoadsorption or plasmapheresis was considered to have a possible adjuvant effect to medical immunosuppressive treatment alone in 44 patients with rapidly progressive glomerulonephritis.Hepatitis C virus (HCV) is common in dialysis patients and renal transplant recipients. In 20 anti-HCV positive sera from 1988-91 recombinant immunoblott assay (RIBA) was positive in 8 cases and indeterminate in 7, while HCV RNA was present in 13/20 tested sera. In October 1991 17% of our hemodialysis patients were verified or suspected carriers while 11% were verified or suspected carriers in January 1997. Genotype 2b was found in 13/24 tested cases and in 7 amplifiable 2b sequences a strong phylogenetic relationship occurred. In 8 out of 12 RIBA-3 indeterminate sera HCV-RNA was still positive. Awareness and preventive measures limited transmission between patients.Indeterminate RlBA-results should, also with modem assays, be regarded with caution due to the relative immunodeficiency of uremic patients.In conclusion renal and systemic diseases may affect the serum immunoglobulins and immunoglobulin G-subclasses, while a study of the specific antibody subclass distributions (anti-HBs) showed no difference in renal (dialysis) patients and healthy adults. Medication (hydralazine) and infection may be triggering factors of various forms of glomerulonephritis. Uremia affects the antibody responses to hepatitis C in dialysis patients. The extent of renal disease as well as the possibility of therapeutic removal of antibodies is also important for the immunologic responses of such disorders.
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| 12. |
- Anderson, Emma S., 1975-
(författare)
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The type IV Oligodendrocyte : experimental studies on chicken white matter
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In mammals, islet amyloid polypeptide (IAPP) is co-produced with insulin in pancreatic ß-cells. In the chicken, the expression of IAPP in the brain is more than 10-fold higher than in the pancreas. We made the fortuitous finding that a polyclonal rabbit antiserum raised against chicken IAPP did not recognise the immunogen, but labelled a subpopulation of oligodendroglia! cells in chicken white matter. The hitherto unknown antigen was called T4-O (Type 4 Oligodendrocyte) since it was localised to the Schwann cell-like Type IV oligodendrocyte of Del Rio-Hortega (1928). This formed a starting point for the present thesis, which is centred on the Type IV oligodendrocyte in chicken white matter.Biochemical analysis of chicken spinal cord showed that the T4-O molecule is a protein with a molecular weight of approximately 100 kDa and an isoelectric point of about 4. Further characterisation has not yet been possible.Immunohistochemical studies on frozen sections revealed that the white matter oligodendrocytes exhibit subpopulations expressing T4-O immunoreactivity strongly, weakly or not at all. Strongly T4-O immunoreactive (IR) oligodendrocytes are co-localised with thick myelinated fibres in the ventral (VF) and lateral funiculi of the spinal cord. A corresponding T4-O immunoreactivity is not found in the fish, the frog, the turtle, the rat and the rabbit.To find out when the T4-0 antigen first appears during development we examined sections from embryonic and post-hatching chicken spinal cords by immunohistochemistry. This showed that the T4-O molecule is first expressed in the VF at embryonic day (E)15, after which the number of IR cells increases with age. Oligodendrocytes cultivated in vitro without or with neurons do not develop a T4-O IR phenotype.These findings called for a closer analysis of the structural development of chicken VF white matter. Electron microscopic (EM) examination revealed a developmental sequence of events principally similar to the development of mammalian white matter, but with a more rapid time course. As seen in the electron microscope the first compact myelin has appeared by E12, when most oligodendrocytes are multipolar. By E15 it seems that these cells have developed a Type IV phenotype, possibly by eliminating some sheaths.Histochemical analysis of Vibratome sections showed that Marchi-positive myelinoid bodies are enriched in white matter areas containing many T4-O IR oligodendrocytes and many large myelinated axons.Examination of the three-dimensional (3D) anatomy of early VF oligodendrocytes in Vibratome slices after 04 labelling or after intracellular injection of a fluorescent dye revealed that these units indeed are Schwann cell-like, with a start length of around 50 µm. We also found that these sheaths expand very rapidly, reaching lengths exceeding 200 µm in three days (E12- E15). The 3D data conformed to our EM evidence that the early oligodendrocytes develop a unipolar Schwann cell-like Type IV anatomy through elimination of some sheaths.To my knowledge the present observations represent the first evidence for an oligodendroglia! heterogeneity in the chicken spinal cord. Differences among oligodendrocytes might, conceivably, explain why inherited disorders of myelin metabolism such as Krabbe's disease, affect some CNS areas more than others.
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| 13. |
- Andersson, Eva, 1946-
(författare)
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Vitamin A and ß-carotene metabolism and effects of UV irradiation in human keratinocytes and melanocytes
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Retinoids (vitamin A and its derivatives) are modulators of proliferation and differentiation. Both retinol (ROH) and its metabolite 3,4-didehydroretinol (ddROH) can be converted to retinoic acid (RA) and 3,4-didehydroretinoic acid (ddRA), ligands for the nuclear receptors, which induce gene transcriptions. A perturbed ROH metabolism is observed in several dermatoses and iu non-melanoma skin cancer. Dietary ß-carotene has been considered to play a critical role in the natural defence against cancer. Whether ß-carotene is converted to ROH in the skin has been debated.We have investigated ß-carotene and retinoid metabolism, retinoid binding proteins and retinoid receptors in human keratinocytes (KCs) and melanocytes (MCs) in vitro. Similar studies of vitamin A have been done in human malignant epithelial cells (HeLa) and malignant melanoma cells. The influence of ultraviolet radiation (UVR) on retinoid metabolism and receptor expression was specially focused upon this thesis. KCs and MCs contained high concentrations of ROH, ddROH, while HeLa- and melanoma cells contained lower levels. KCs contained the highest level of the retinoid-binding proteins CRBP I and CRABP II compared to MCs, HeLa and melanoma cells. High CRABP II levels showed a correlation with the ability to accumulate ddROH. In MCs, CRABP I was highly expressed, but in melanoma cells CRABP II dominated. The difference between MCs and melanoma cells in receptor levels was most pronounced for RARß, which was highly expressed in melanoma cells. Such dissimilarities between benign and malignant MCs might play a role in differentiation and growth regulation. The uptake of [3H]ROH, [3H]RA and ß-carotene was significantly higher in MCs than in KCs. We were able to demonstrate that [14C]ß-carotene was converted to [14C]ROH in both these cell types. This suggests that this local storage of ß-carotene might serve as au alternative supply for vitamin A in the skin.A moderate dose of UVR reduced the concentration of ROH, ddROH and [3H]RA in KCs and MCs by 20-50%. The concentration returned to starting levels in 1-2 days, and could be explained by a retarded metabolism of RA, the biologically most active metabolite. When KCs and MCs were exposed to UVR, the mRNA and protein levels of the three nuclear retinoid receptors (RARα, RARγ and RXRα) decreased rapidly. In MCs these levels were close to normal 3 days postirradiation. In KCs only the RARα mRNA and protein levels returned to baseline within 3 days. This thesis has increased our knowledge of the effects of UVR on retinoid metabolism and retinoid receptors in human cells. Further studies are needed to understand the role of ß-carotene and retinoid signaling in UV induced skin cancer.
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| 14. |
- Andersson, Peter, 1957-
(författare)
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Surgery and anorectal function in Crohn's colitis
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The study concerns surgery in Crohn's disease, particularly Crohn's colitis, its relation to medical treatment, symptomatic load, perceived health, quality of life, outcome on anorectal function and also anorectal physiologic conditions.Four hundred and thirty-two patients treated at the University Hospital, Linköping from 1970 to 1997 were included in the study. Operations and medical treatment were retrospectively reviewed, whereas symptomatic load, perceived health, quality of life, function outcome and anorectal physiology were prospectively evaluated.In a cross-sectional analysis of all patients surveilled 1995 the annual incidence of surgery was 5.7% in a population-based cohort and 10.3% in referred patients. Medical maintenance treatment was used in 61 and 55% respectively. This led to 89% of the patients being in clinical remission or having only mild symptoms and to a large proportion with a perception of good health. The treatment was paralleled by a low rate of septic and surgical complications.Surgical treatment of Crohn's colitis prior to 1990 mainly implied colectomy or proctocolectomy and thereafter almost exclusively segmental resection. The creation of a permanent stoma decreased and was rarely needed at the end of the study period when the annual risk was 0.23%. This development was basically due to a deliberate change in surgical attitude aiming at introducing similar treatment principles as for small bowel Crohn's disease With limited resections and preservation of transanal defecation. The reduced colectomy rate may have been facilitated by the introduction of immunosuppressive medical treatment as a reduction of colectomies tended to be associated with medical maintenance treatment during the later part of the study. Time from diagnosis to surgery was prolonged and stricture replaced active disease as the major indication for surgery. Symptomatic load and anorectal function outcome were better after segmental resection without the expense of an increased reresection rate. Seventy percent of patients with Crohn's colitis were in clinical remission and these patients scored quality of life similar to the general population but patients with active disease scored worse in all indexed aspects. The need of immunosuppression or previous surgery was not related to quality of life except when operated with a permanent stoma which negatively influenced psychological well being.Anorectal physiology in Crohn's disease differed from controls with increased anal resting pressures and increased rectal sensitivity. This provides possible prerequisites for later development of anal pathology such as fissures and fistulas.The study indicates that the concept oflimited surgery is applicable also in Crohn's colitis with obvious benefits for the patients. A treatment concept including medical maintenance treatment and limited resections implies that the vast majority of patients with Crohn's disease may live with only minor symptoms and minimal risk of having a permanent stoma, factors associated with a quality of life similar to that of the general population.
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| 15. |
- Andersson, Tony P. M., 1973-
(författare)
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Melanophore signaling : regulation and application
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Melanophores are pigment-containing cells responsible for quick physiological color changes in lower vertebrates due to redistribution of melanosomes, pigment granules. We have studied melanophores from African clawed frog, Xenopus laevis. Classically, melanosomes can be stimulated to aggregate in the cell center by the hormone melatonin via a process involving activation of the inhibitory Gi/o protein and inhibition of adenylate cyclase/cAMP/protein kinase A pathway. In addition, tyrosine phosphorylations have been shown to be crucial for aggregation. In this thesis, we demonstrate that mitogen-activated protein kinase (MAPK) are activated and phosphoinositol 3-kinase (PI3-K) are involved in melatonininduced aggregation. Inhibition of MAPK kinase or PI3-K inhibits MAPK activation, tyrosine phosphorylation of a 280-kDa protein and aggregation. Further, PI3-K inhibition is less dramatic in fish Labrus melanophores. Together with findings that phosphodiesterase (PDE) 4 and/or PDE2 are involved in keeping the aggregated state in Xenopus, we suggest that active PI3-K via MAPK stimulates PDE, thus lowering cAMP. We also use latrunculin A to induce aggregation via disruption of actin filaments. Kinetic studies indicate that melatonin and latrunculin share final downstream target, possibly inactivate myosin-V leading to melanosome aggregation. As biosensor application, a new computer screen assisted technique suitable for bioassays is demonstrated using melanophores to monitor kinetic responses of melanosome movement and blood plasma sample detection of the asthma drug and ß2 adrenergic agonist formoterol. We also used melanophores to examine the efficacy of enantiomers of formoterol. We confirm that (R;R)-formoterol is more potent than (S;S)-formoterol, in guinea pig tracheal ring preparations, cultured melanophores, and radioligand binding on COS-7 cells, but demonstrate and calculate that (S;S)-formoterol has more efficacy than previously described. Characterization of melanophores are important for biosensor applications, i e to understand mechanisms of drugs, and will probably also increase the knowledge of cell signaling in other cell systems.
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| 16. |
- André, Malin, 1949-
(författare)
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Rules of Thumb and Management of Common Infections in General Practice
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis deals with problem solving of general practitioners (GPs), which is explored with different methods and from different perspectives. The general aim was to explore and describe rules of thumb and to analyse the management of respiratory and urinary tract infections (RTI and UTI) in general practice in Sweden. The results are based upon focus group interviews concerning rules of thumb and a prospective diagnosis-prescription study concerning the management of patients allocated a diagnosis of RTI or UTI. In addition unpublished data are given from structured telephone interviews concerning specific rules of thumb in acute sinusitis and prevailing cough.GPs were able to verbalize their rules of thumb, which could be called tacit knowledge. A specific set of rules of thumb was used for rapid assessment when emergency and psychosocial problems were identified. Somatic problems seemed to be the expected, normal state. In the further consultation the rules of thumb seemed to be used in an act of balance between the individual and the general perspective. There was considerable variation between the rules of thumb of different GPs for patients with acute sinusitis and prevailing cough. In their rules of thumb the GPs seemed to integrate their medical knowledge and practical experience of the consultation. A high number of near-patient antigen tests to probe Streptococcus pyogenes (Strep A tests) and C-reactive protein (CRP) tests were performed in patients, where testing was not recommended. There was only a slight decrease in antibiotic prescribing in patients allocated a diagnosis of RTI examined with CRP in comparison with patients not tested. In general, the GPs in Sweden adhered to current guidelines for antibiotic prescribing. Phenoxymethylpenicillin (PcV) was the preferred antibiotic for most patients allocated a diagnosis of respiratory tract infection.In conclusion, the use of rules of thumb might explain why current practices prevail in spite of educational efforts. One way to change practice could be to identify and evaluate rules of thumb used by GPs and disseminate well adapted rules. The use of diagnostic tests in patients with infectious illnesses in general practice needs critical appraisal before introduction as well as continuing surveillance. The use of rules of thumb by GPs might be one explanation for variation in practice and irrational prescribing of antibiotics in patients with infectious conditions.
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| 17. |
- Aniansson Zdolsek, Helena, 1961-
(författare)
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Maturation of T-lymphocytes and monocytes in children in relation to development of atopic disease
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bakgrund: Atopiska sjukdomar har ökat i västvärlden under de senaste årtiondena. För att förstå den bakomliggande mekanismen vid sensibilisering mot allergen behöver vi förbättra vår kunskap av T-lymfocyters och monocyters utmognad hos små bam.Mål: Att prospektivt studera utmognaden av T-lymfocyter och monocyter hos bam som senare utvecklade atopisk sjukdom.Material och metoder: 170 barn med och utan atopisk sjukdom i familjen följdes från födelsen till 18 månaders ålder, och 38 av dessa följdes också upp vid sju års ålder. Förekomst av atopisk sjukdom under uppväxten(= kumulativ sjukhistoria) registrerades. En hudpricktest (SPT) utfördes vid 18 månader och vid sju års ålder. Markörer för ytreceptorer på T-celler (CD2, 3, 4, 8, 28) studerades med hjälp av flödescytometrisk teknik på alla bam vid födelsen och vid 18 månaders ålder. Dessa markörer studerades också vid 3, 6 och 12 månaders ålder i en undergrupp om 78 barn med stark familjär ärftlighet för atopisk sjukdom, eller avsaknad av sådan. Vid 18 månaders ålder deltog 54 barn, 29 icke-atopiska och 25 atopiska, i en funktionell T-cellsstudie. Proliferation av perifera mononukleära celler i blodet (PBMN celler) studerades med inmärkning av 3H-tymidin efter stimulering med anti-CD3 eller phytohemagglutinin (PHA). Anti-CD3 inducerad cytokin produktion (IL-4, IL-5, IL-6, IL-10, IL-13 och IFN-γ) rutalyserades med ELISA teknik (enzyme-linked immuno sorbent assay). Vid sju års ålder följdes 38/54 bam upp och IL-12 svaret hos PBMN celler studerades efter att stimulering med IL-2, IL-12 eller båda. Uttrycket av 1L-12Rß2 mRNA mättes med real-tids PCR (polymerase cltain reaction), medan cytokin-nivåer IL-5, IL-10 och IFN-γ mättes med ELISA. På 76 barn studerades monocyt-mru·kören CD14 med flödescytometrisk teknik, lösligt CD14 i serum (sCD14) med ELISA och total-nivåer av immunglobulin E (lgE) med UniCAP® vid födelsen, 3, 6, 12 och 18 månaders ålder. Vid sju års ålder rutalyserades också sCD14 och total-IgE hos 38 barn.Resultat: Vid 18 månaders ålder var 118/170 barn icke-atopiska och 31/170 hade utvecklat atopisk sjukdom. CD4 FI på T-hjälpar (CD3+CD4+) celler var lägre vid födelsen och vid 3 månaders ålder hos barn med en atopisk kumulativ sjukhistoria vid 18 månaders än hos ickeatopiska. Atopi var också förenat med en låg andel av CD2+ lymfocyter vid 18 månaders ålder. Vid samma ålder hade barn med kumulativ sjukhistoria och en positiv SPT lägre CD2, liksom lägre CD3 FI på pan T (CD3+CD45+CD14-) celler och högre CD28 FI på CD2+CD8+CD28+ celler. Atopisk sjukdom vid 18 månader var förenat med högre nivåer av anti-CD3 inducerad IL-5 sekretion och SPT- barn med atopisk sjukdom producerade högre nivåer av IL-l O än SPT + barn. Kvoten av IL-4/ IL-l O och IL-4/ IFN-γ var högre hos barn med förhöjda nivåer av total IgE. Barn med atopisk sjukdom och atopiska luftvägssymptom uppreglerade uttrycket av IL-2 inducerad IL-I2Rß2 mRNA mindre än icke-atopiska brun vid sju års ålder. De hade också en lägre IL-2 och IL-12 inducerad IFN-y sekretion. Vidare var sCD14 lägre vid sju års ålder hos barn med en atopisk kumulativ sjukhistoria, än hos ickeatopiska barn. Detta mönster observerades också vid 3 och 18 månader hos SPT+ barn med kumulativ atopisk sjukhistoria vid 18 månaders ålder jämfört med SPT- icke-atopiska barn. Dessutom hade barn med mycket allergi i familjen lägre nivåer av sCDI4 vid 3, 12, och 18 månader och vid 7 års ålder än bam utan allergi i familjen.Sammanfattning: Utmognaden av T celler och funktionen av dessa skiljer sig mellan atopiska och icke-atopiska barn. IL-12 svaret hos barn med atopiska luftvägssymptom och höga nivåer av total-IgE är reducerat. Sammantaget kan detta bidra till ett T-hjälpar 2 devierat humunsvar vid atopisk sjukdom. Atopiska barn har lägre nivåer av sCD14. De låga nivåerna kan möjligen vara en konsekvens av familjär atopisk ärftlighet/atopisk sjukdom och kan kanske också avspegla en minskad förmåga att svara på mikrobiella signaler hos atopiska individer.
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| 18. |
- Bachrach-Lindström, Margaretha, 1957-
(författare)
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Nutritional status and functional capacity in elderly people with hip fracture
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim was to study nutritional status and functional capacity in elderly men and women admitted to hospital with a hip fractnre, and to evaluate the effect of nutritional intervention and surgical method. A total of 176 patients participated in the study. Of them 84 received protein- and energy-enriched meals at hospital and nutritional advice on discharge and at home. A total of 100 patients with displaced femoral neck fracture were randomised to treatment with either total hip arthroplasty or osteosynthesis with Olmed® screws.The patients were examined and interviewed the first time within 4-6 days after surgery, as well as one and three months aud one year after surgery. The nutritional status was assessed with body mass index, measures of triceps skinfold thickness, estimation of muscle mass and body composition. Serum albumin, insulin-like growth factor-I and hormones were measured. Functional capacity was assessed with the Modified Norton scale, Katz index of ADL and a questionnaire measuring instrumental activities of daily living.Mentally impaired patients had worse nutritional status aud functional condition compared with the lucid group at inclusion, deteriorated more in activity and mobility fimctions and had a higher one-year mortality rate. The nutritional intervention was not powerful enough to have effect on anthropometric or biochemical measurements. The patients treated with total hip arthroplasty had reduced pain, better locomotion ability and a slight weight gain compared with the osteosynthesis group.In conclusion, a marked deterioration of nutritional and functional status was found after a hip fracture. Studies of the effect of a more powerful nutritional intervention on nutritional status and functional capacity in this group are warranted. Patients treated with total hip arthroplasty had a more favourable rehabilitation period with regard to nutritional status and locomotion ability.
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| 19. |
- Barral, Anna-Maria, 1963-
(författare)
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Immunological Studies in Malignant Melanoma : Importance of TNF and the Thioredoxin System
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Malignant melanoma is a tumor whose incidence is dramatically increasing in persons with light-coloured skin in all parts of the world. Due to its resistance against traditional chemo- and radiotherapy, melanoma has been a favourite target of alternative therapies, in particular those involving immunological mechanisms. Cytokines and particularly tumor necrosis factor (TNF) have been studied as possible antitumoral agents, but also as endogenous growth or differentiation factors. Previous studies showed that melanomas could express TNF in situ and that this expression correlated to decreased lymphocyte infiltration. On the other hand, redox reagents can modulate expression of cytokines, and the thioredoxin (Trx) system is particularly known to influence expression and secretion of TNF in vitro.The overall aim of this research was to explore immunological aspects of melanoma, particularly the role of TNF both in vitro and in vivo, as well as its possible modulation by Trx.In the in vitro studies first we developed a novel method for obtention of monoclonal antibodies against melanoma antigens, and generated and characterized specific monoclonal antibodies against both full-length and truncated Trx. We studied the cytokine expression of a panel of normal and transformed melanocytic cells by immunofluorescence, all of which presented TNF and Trx at levels comparable to monocytic cells, and TNF-receptors (TNFR) at low but detectable levels. Melanoma cells did not secrete TNF upon stimulation in spite of its presence in the Golgi apparatus. However, melanoma cells expressed the TNF-processing enzyme TACE and were capable of cleaving transfected GFP-tagged TNF. Imaging studies point to a possible cell-cell tranfer of endogenous TNF in melanoma cells.On the other hand, TNF and Trx expression in melanoma cell lines correlated to resistance against exogenous TNF. We studied then the in situ expression of TNF and Trx by immunohistochemistry in a group of 44 cutaneous melanoma patients. Trx expression did not correlated to survival or other clinicalpathological parameters. TNF expression significantly correlated to better survival in tumors thicker than 0,8 mm, and constituted an independent prognostic factor.These results point to a biological role of endogenous TNF in malignant melanoma, either by constituting an autocrine/paracrine differentiation factor or by modulating communication with other cell types, particularly of the host’s immune system.
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| 20. |
- Bengtson, Per
(författare)
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Carbohydrate dependent adhesion of leukocytes and the role of fucosyltransferase VII
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Galectins, E-and P-selectins are carbohydrate-binding proteins that are up regulated at inflammatory lesions. Selectins expressed ou the activated endothelium mediate transient binding to leukocyte ligands that require sequential action of α 2,3-sialyltransferases and a 1,3-fucosyltransferases. ln leukocytes α1,3 fucosyltransferase VII adds fucose to α 2,3- sialylated lactosarnine acceptors in the final step of the biosynthesis of the selectin binding epitope sialyl Lewis x.The finding of low sialyl Lewis x expression in polymorphonuclear leukocytes from a patient with ulcerative colitis led to the discovery of a missense mutation (G329A) in the human gene coding for α1,3 fucosyltransferase VII, FUT7. Studies including enzymatic and immunochemical analysis oftransfected cell lines and isolated polymorphonuclear leukocytes from patients confirmed that this mutation impair the ability of α1,3 fucosyltransferase VII to synthesize sialyl Lewis x. The frequency of the mutation were measured in a mixed Swedish population and found to be -1 %. One individual carrying the FUT7-G329A mutation homozygously was identified. This individual suffered from ulcer disease, noninsulin-dependent diabetes, osteoporosis, spondyloarthrosis, and Sjögren's syndrome, but the relationship between disease and the mutation is not established.Studies using an in vitro flow chamber assay showed that transfected B-lymphoma cells and Epstein-Barr virus transformed B cells only transcribing FUT7-G329A were not able to interact with E-selectin during flow whereas polymorphonuclear leukocytes from the FUT7-G329A homozygous individual interacted well with both P- and E selectin during flow. The mRNA level of the fucosyltransferase IV coding gene, FUT4, was found to be elevated in the homozygous individual, which resulted in elevated levels ofthe CD65s epitope. However, transfected B-lymphoma cells and Epstein- Barr virus transformed cells did not show a similar elevation of FUT4 mRNA. In in vitro studies galectin-1 and- 3 were observed to be able to recruit polymorphonuclear leukocytes during flow. This thesis gives further insight into the molecular mechanisms leading to carbohydrate dependent dynamic adhesion between polymorphonuclear leukocytes and lectins during inflammation.
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