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  • Druid, Henrik (författare)
  • Experimental acute ischemic renal failure and anticoagulation
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>This thesis is based on experimental studies on acute renal failure (ARF) in rats. The model employed is that of renal artery clamping, which causes a standardized, ischemic trauma to the kidney. The proximate objective of the investigations was to study iflocal coagulation in the kidney may be induced by a pure ischemic trauma, and whether such a coagulation could be of importance for the development of ARF in this experimental model.</p><p>The content of isotope-labeled fibrinogen and albumin was determined in postischemic kidneys and controls. After 60rnin of unilateral ischemia, the fibrin(ogen)/degradation products (FIB) and albumin content of the kidney increased rapidly and significantly, approximately averaging 200% of controls. The total kidney weight increased only to 130% of controls. Pretreatment with heparin in a dose of 2000 IU/kg BW, markedly attenuated the increase in kidney weight and content of FIB and albumin.</p><p>Pretreatment with a lower dose of heparin, 400 IU!kg BW, and warfarin (given intraperitoneally 24 h before the experiment) produced a similar reduction of these parameters, whereas pretreatment with a heparin analog, devoid of anticoagulant effect, did not.</p><p>In post-ischemic kidneys, scanning electron microscopy (SEM) of cautiously handled freezedried tissue revealed granular and fibrillary material in the tubules and in Bowman's space, at some locations displaying prominent network patterns. Immunofluorescence against FIB showed immunoreactive material in vasa recta, the peritubular capillaries, Bowman's space and in the tubules. By transmission electron microscopy (TEM), fibrin strands lacking periodicity were seen. As compared to controls, the postischemic kidneys generally showed a marked dilatation of Bowman's capsule. No fibrin deposition was seen in heparin pretreated animals.</p><p>To determine if anticoagulation exerts the described effects by prevention of tubular obstructions or by attenuation of increased glomerular permeability, morphometry of glomeruli was performed by light microscopy and TEM Postischemic kidneys from rats pretreated with saline showed a marked widening of Bowman's space, most likely due to tubular obstruction, whereas Bowman's space width in anticoagulated rats did not differ from controls. Structural changes of the podocyte foot processes as a marker of increased macromolecular permeability were severe in both saline pretreated and anticoagulated kidneys.</p><p>Glomerular filtration rate fell to 6% of controls after 40 min of ischemia. Warfarin-pretreatment attenuated this decrease significantly. Urinary protein excretion increased in both salinepretreated and anticoagulated rats. The excretion of FIB was significantly increased in warfarinpretreated rats, consistent with the previous observation of an attenuation of FIB content of postischemic kidneys by anticoagulation. This result thus suggests that warfarin did not prevent macromolecular sieving, but reduced the formation of protein-containing tubular casts.</p><p>In summary, these studies show that a pure ischemic injury to the kidney results in a local coagulation in the kidney, most prominently within Bowman's space and in the tubules. It is suggested that the increased glomerular permeability to macromolecules causes sieving of fibrinogen, which may precipitate in Bowman's space and tubuli and promote the development of tubular obstructions.</p>
  • Duchén M., Karel, 1961- (författare)
  • Human milk factors and atopy in early childhood
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p><strong>Background</strong>: The protective effect of breast milk against atopic manifestations in infancy, i. e. atopic eczema and food allergy, has been controversial for the last decades. Differences in the composition of human milk could explain these controversies.</p><p><strong>Aims</strong>: To investigate the composition of milk antibodies, such as lgE, total S-IgA and S-IgA antibodies against food and inhalant allergens (B-lactoglobulin, ovalbumin and cat allergen) in milk from atopic and non atopic mothers. To study human milk nucleotide, polyamine and polyunsaturated fatty acid (PUFA) composition. Furthermore, the composition of these factors in maternal milk were related to the development of allergic disease in the children during the first 18 months of life.</p><p><strong>Methods</strong>: One hundred and twenty (120) children were followed at 3, 6, 12 and 18 months of age. Blood samples were obtained at birth and at 3 months. Skin prick tests were petformed at 6, 12 and 18 months and the development of atopic diseases was assessed in the children. Breast milk samples were collected from their mothers at birth and monthly dming the lactation period. Total IgE antibodies were measured by RIA and S-IgA antibodies by ELISA. Milk nucleotides and polyamines were measured by HPLC and PUFA by gas chromatography.</p><p><strong>Results</strong>: Total IgE and total S-IgA levels were similar in colostrum from atopic and non atopic mothers, Total S-IgA levels were, however, lower in mature milk from atopic than from non atopic mothers. Levels of S-IgA antibodies against foods and cat, were similar in the two groups during the lactation period, except for low levels of anti-OVA S-lgA in colostrum of atopic mothers. Nucleotide composition was similar in milk from atopic and non atopic mothers. Low levels of putrescine and spermine were, however, found in mature milk from atopic mothers.</p><p>Low levels of LA, LNA, n-6 LCP and n-3 LCP and particularly higher LAILNA and AA!EPA ratios were found in milk from atopic mothers at one month of lactation. Correlations between individual LCP levels were observed in milk from non atopic mothers. These correlations were absent in milk from atopic individuals, indicating a disturbed PUFA metabolism. The differences were less obvious in serum phospholipids from newboms.</p><p>Total lgE, total S-IgA and S-IgA antibodies against foods and cat, as well as nucleotide and polyamine levels were similar in milk from mothers of allergic children. Lower levels of EPA in transitional milk and lower levels of EPA, DPA and DHA (p&lt;0.05 for all) in mature milk were found in mothers of allergic as compared to mothers of non allergic children. Total n-6/total n-3 and AA/EPA ratios were low in both transitional and mature milk from mothers of allergic children. The disturbed correlations within the n-6 fatty acids in milk from atopic mothers were not related to the development of atopy in the children. In contrast, C20:4 n-3 correlated well to most of the n-6 fatty acid levels only in milk from non atopic mothers of non atopic children.</p><p>The PUP A levels in serum from allergic and non allergic children were similar, except higher levels of C22:4 n-6 and C22:5 n-6 (p&lt;0.05 for both) and higher AA!EPA ratio in serum phospho1ipids from the former group (p&lt;0.05). Changes in levels of milk PUFA were reflected in changes in PUFA serum phospholipids, particularly for the n-6 PUPA. The AA!EPA ratio in maternal milk was related, however, to the AA/EPA only in serum from non allergic children, while this was not the case in allergic children.</p><p><strong>Conclusion</strong>: Low levels of anti-QV A S-IgA antibodies in colostrum and low levels of total S-IgA, putrescine and spermine in mature milk. were related to maternal atopy. Human milk IgE antibody and nucleotide composition were not related to maternal atopy. Neither of these milk factors were, however, related to development of anergic disease in children. Low levels of n-6 and n-3 PUFA in transitional milk were related to maternal atopy, particularly low levels of n-3 PUP A and high AA/EPA ratio in maternal milk and serum phospholipids in the infants were related to the development of allergy in the children. The milk PUPA composition influenced the composition of PUPA in serum phospholipids of the children. The findings are suggested to be partly related to a 8-6 desaturase dysfunction in atopic individuals.</p>
  • Edell-Gustafsson, Ulla, 1947- (författare)
  • Sleep, psychological symptoms and quality of life in patients undergoing coronary artery bypass grafting
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>In this thesis sleep, psychological symptoms and quality of life (Qol) in patients undergoing coronary artery bypass grafting (CABG) at the University Hospital in Linköping were evaluated. Interviews and 24-hour polysomnography were performed prior to surgery, immediately after surgery and again at one month, with a six-month-follow-up mailed questionnaire. Habitual sleep was evaluated using the Uppsala Sleep Inventory questionnaire and a diary the recorded mornings. The Spielberger State of Anxiety Scale and the Zung's Self-rating Depression Scale were used to measure anxiety and depression, respectively. Physical functional capacity was assessed according to the New York Heart Association's (NYHA) classes and Qol, with the Nottingham Health Profile instrument (NHP).</p><p>A retrospective evaluation of nurse's documentation about sleep was also performed. In addition, the quality and quantity of sleep were assessed before surgery and in the immediate postoperative period in a pilot study, with a one-month follow-up interview. The results indicated disturbed sleep, and changes in behaviour and mental state after surgery due to fragmented sleep, pain and anxiety.</p><p>Forty-four patients were examined prior to surgery. The results showed that almost two-fifths experienced too little sleep habitually and 50 % had a combination of at least two sleep problems. Poorer health, higher level of anxiety and increased difficulties maintaining sleep (DMS) were consistent with significantly longer sleep latency, increased fragmented sleep, and reduced stages 3 and 4 and RIM sleep measured by polysomnography. The level of Qol on the NBP was significantly associated with objectively measured sleep.</p><p>In the immediate period following CABG there is a changed distribution of sleep, with a reduction of nocturnal sleep duration and an increase in daytime sleep, which had almost returned to preoperative values one month after surgery. Qol was significantly improved six months after surgery compared to before surgery.</p><p>It was noted that patients with a more anxiety prone reactivity during six months following CABG had significantly more sleep disturbances, reduced energy and functional physical capacity, and lower quality of life, compared to those without such reactivity. Significantly more sleep disturbances, reduced energy and lower quality of life were more prominent among those with sadness/depression or cognitive/behavioural fatigue as reactions to sleep loss. A higher degree of cognitive/behavioural fatigue and dysphoria reactions were associated with a higher NYHA class.</p><p>In conclusion, patients with coronary artery disease have poor quantity and quality of sleep. Increased psychological symptoms in patients with CAD prior to surgery were associated with greater symptoms six months after surgery. Physical functional capacity and quality of life were significantly improved six months after surgery.</p>
  • Ekerfelt, Christina, 1957- (författare)
  • Interferon-Υ and interleukin-4 in health and disease : Studies on <em>Borrelia</em> infection, inflammatory polyneuropathies and normal pregnancy
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p><strong>Background</strong>: The immune system needs stringent regulation in order to effectively eliminate infecting agents and, at the same time, protect the body from immunemediated tissue destruction. T cells have a major role in this regulation by secreting cytokines. Interferon-y (IFN-y) and interleukin-4 (IL-4) exert antagonistic regulatory functions and are mutually inhibitory. Thus, immune responses are generally functionally dominated by IFN-y or IL-4, a balance which is believed to be decisive for the outcome. Besides providing protection against pathogens, the immune system also has impact on several other conditions, e. g. reproduction and inflammatory diseases. Much is known about the role of IFN-y and IL-4 in animal models of these conditions, but less data are available from studies in humans. Data on IL-4 secretion are particularly rare, since this cytokine is extremely hard to detect.</p><p><strong>Material and methods</strong>: Antigen-specific secretion of IFN-y and IL-4 was detected with ELISPOT -technique in different human conditions, including Borrelia-infection, inflammatory diseases in the peripheral nerves (the Guillain-Barre syndrome [GBS] and polyneuropathy associated with monoclonal gammopathy [PNMGUS]) and normal pregnancy. A novel assay was developed for the detection of fetus-specific cytokine secretion during pregnancy. Finally, a therapeutical approach for selective redirection of inappropriate IFN-y secretion to IL-4 secretion was developed in an experimental model of GBS.</p><p><strong>Results</strong>: Predominant Borrelia-specific secretion of IFN-y and low or absent IL-4- secretion was found, both in patients with clinical Borrelia-infection and resistant individuals. A compartmentalization of this secretion to the central nervous system was evident in patients with neuro-borreliosis. There were indications that the specific IL-4 secretion increased over the disease course, and of lower numbers of Borrelia-specific IL-4 secreting cells in patients that did not fully recover compared with those who did. This suggests that Borrelia-specific IL-4 secretion might be necessary to down-regulate the inflammatory responses generated by IFN-y. Patients with a chronic disease course appeared to have a larger proportion of spontaneously IL-4 secreting cells compared with resistant individuals. Thus, individuals who develop chronic borreliosis may have limited ability to mount strong IFN-y secretion, which may be needed initially in the infection for eradication of the Borrelia bacteria.</p><p>An increase in the secretion of IL-4 in response to paternal but not to unrelated anaantigen was found in the blood of pregnant women. This is an extraordinary finding, since allo-reactivity usually is predominated by IFN-y secretion. The secretion of IL-4 exclusively to paternal allo-antigen, suggests that this is primarily selective for the fehls. Thus, responses to antigens that are not present at the maternal-fetal interfaCe may well be IFN-y predominated, which is needed to combat common infections. Auto-reactive secretion of IFN-ywas found in PNMGUS, which is a chronic disease. Conversely, autoreactive secretion of IL-4, associated with recovery, was detected in the self-limiting disease GBS. This supports the hypothesis that auto-reactive IFN- )' secretion is involved in the pathogenesis of organ-specific inflammatory diseases, whereas IL-4 secretion is beneficial.</p><p>Transfer of syngenic disease-specific cells, which had been ex vivo deviated to predominant secretion of IL-4, significantly ameliorated the disease in the experimental model of GBS. This may become a feasible approach for therapeutic intervention of organ-specific inflammatory diseases.</p><p><strong>Conclusions</strong>: The ELISPOT-technique successfully detected alterations in the spontaneous as well as the antigen-induced secretion of IFN-y and IL-4, which a1so in humans appears to have implications for health and disease.</p>
  • Enskär, Karin (författare)
  • Assessing the life situation of children and adolescents with cancer and their families
  • 1997
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>In recent decades, more children have been cured of cancer due to research development and intensification of treatment. Having a life-threatening disease, like cancer, during childhood effects both the child and the family. It is important for the staff working with those families to know what is distressing in order to provide appropriate care. The aim of this thesis was to develop instruments to assess the life situation of children with cancer and their families. First, the health care personnel's (n=24) perception of problems and symptoms caused by the disease were identified. An inquiry of Delphi-technique type was used. The results gave two Lists of Problems (LoP), one with 84 problems concerning the child, and one with 69 problems concerning the rest of the family. In the next study, using qualitative interviews, children's (n~5), adolescents' (n~10) and parents' (n~16) own experience of problems related to the disease and its perceived effect on their life situation were investigated. The result from those studies formed the basis for the three scales developed in the study, the Life Situation Scales for Children 7-12 years old (LSS-C), for Adolescents 13-19 years old (the LSS-A) and for Parents (the LSS-P). A new group of children (n~15), adolescents (n~21) with cancer and their parents (n~llO) answered one of the three questionnaires. The psychometric tests of the first version of the life situation scales gave some evidence of validity and reliability. However the scales for children and adolescents, in particular, need to be tested on larger samples. The study indicated how to proceed with futher development, as the methods used seemed to be adequate. After further development the tools could be used in research and clinical care evaluations.</p>
  • Ericson, Ann-Charlott, 1965- (författare)
  • Synaptic organization of nociceptive relay nuclei in the cat and primate thalamus
  • 1996
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>The fine structure of two thalamic nociceptive relay nuclei, the nucleus submedius (Sm) in the cat, and the posterior region in the owl monkey, was investigated using anatomical tract tracing techniques, immunohistochemical staining for neuroactive substances, and threedimensional reconstructions of synaptic circuitry.</p> <p>Ascending lamina I axons, labeled by anterograde transport of Phaseolus vulgaris leucoagglutinin, gave rise to two different types of termination in Sm: large, compact clusters of numerous boutons were predominant in the dense focus of the terminal field after a tracer injection at the site of nociceptive-specific neurons in lamina I, and boutons-of-passage type terminations were conspicuous in the periphery of a lamina I terminal field in Sm and predominant following a tracer injection at the site of thermoreceptive-specific neurons in lamina I. Three-dimensional reconstructions of a sample of these terminations, generated from series of ultrathin sections by using special software on a computer workstation, showed that all boutons of each cluster made synaptic contact with protrusions and branch points on a single dendrite. These contacts involved presynaptic dendrites (PSDs) in triadic arrangements. In contrast, the boutons-of-passage type terminations were generally characterized by contacts with PSDs, and some of the passing varicosities made simple such synaptic contacts. However, an intermediate termination pattern was also found in which boutons-of-passage fanned synaptic complexes with dendritic appendages involving PSD contacts.</p> <p>Postembedding immunogold-labeling techniques showed that the spinal and trigeminal terminals in Sm contained synaptic vesicle-associated glutamate, suggesting that glutamate is an excitatory neurotransmitter in these terminals. Corticothalamic tract terminals were also glutamatergic. Immunoreactivity to gamma-aminobutyric acid (GABA) was observed in PSDs originating from GABAergic intrinsic neurons and in axon tenninals supposed to originate from the reticular thalamic nucleus. A similar organization of glutamatergic and GABAergic elements was seen in the posterior thalamic region of owl monkeys.</p> <p>The different types of synaptic organization seen in Sm are consistent with the possibility that modality-selective nociceptive and thermoreceptive lamina I neurons terminate differentially in this nucleus and suggest a functional integration of cold and pain activity. The presentfindings provide evidence that such activity is transmitted by the excitatory amino acid glutamate and is modulated by inhibitory GABAergic mechanisms. Glutamate and GABA are also involved in the processing of ascending information in the posterior thalamic region of owl monkeys, showing that these substances are important for pain transmission in primates as well.</p>
  • Eriksson, Per, 1958- (författare)
  • Renal disease in primary Sjögren's syndrome
  • 1996
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Primary Sjögren's syndrome (SS) is characterised by inflammation in the lacrimal and salivary glands. The kidneys may be involved, e.g. tubulointerstitial nephritis (TIN) and distal renal tubular acidosis (dRTA). dRTA is often associated with hypocitraturia, and both represent risk factors for the development of urolithiasis. The present investigations were undertaken to evaluate renal tubular function (including -dRTA), glomerular filtration rate (GFR), renal histopathology and mechanisms of stone formation, as well as the serum IgG subclass pattern in patients with SS. Furthermore, patients presenting with urolithiasis and dRTA in absence of sicca symptoms, as well as patients with urolithiasis andhypocitraturia, were studied with respect to autoantibodies and clinical features of SS.</p> <p>Renal tubular dysfunction, such as dRTA; impaired urine concentrating ability; hypocitraturia; and decreased tubular reabsorption of phosphate (1RP%), was conunonly detected in the SS-patients. Tubular proteinuria (al-microglobulin) and tubular enzymuria (NAG) were primarily associated with decreased GFR.</p> <p>GFR, investigated with 5Icr-EDTA plasma clearance, was below the reference limit in 33% of SS-patients. An inverse correlation was found between GFR and the extent of tubulointerstitial nephritis (adjusted CTIN score). Decreased GFR was mostly due to TIN, although urolithiasis and upper urinary tract infections may have contributed in some patients.</p> <p>TIN was demonstrated in most biopsied patients with SS, and the histopathological picture was characterised by mainly focal interstitial inflanunation, tubular atrophy, interstitial fibrosis and a varying extent of glomerular sclerosis.</p> <p>Fourty-one percent of the SS-patients had formed at least one stone, and calcium phosphate was the main constituent in most stones. All stone formers had dRTA, and most of them had hypocitraturia. Urinary calcium and urate excretion was also significantly higher than in non-stone formers.</p> <p>The SS-patients often had low serum levels of IgG2, despite high levels of total IgG. Low levels of IgG2 were sometimes associated with infections. A high IgG lngG2 ratio indicated autoimmune disease.</p> <p>Of 10 patients presenting with urolithiasis and dRTA, anti-SS-A antibodies were detected in eight. Subjective sicca symptoms subsequently developed l-48 years after the presentation of urolithiasis, and objective signs of SS were found in 7 patients.</p> <p>In a large population of hypocitraturic stone formers, ANA and anti-SS-A antibodies were commonly detected in the women but not in the men. Four of 14 evaluated hypocitraturic women with anti-SS-A antibodies or ANA, fulfilled the criteria for SS.</p> <p>In conclusion, the present investigations show that 24-hour urinary excretion of citrate is a valuable tool for detection of renal disease in SS, slightly-moderately decreased GFR is not unusual in SS-patients with. renal disease, the "adjusted CTIN score" can be a useful tool for quantifying the extent of tu'bulointerstitial nephritis, and the urine composition in stone formers with SS is similar to that of other dRT A-patients.</p> <p>The possibility of a Sjögren-related renal disease charcterised by urolithiasis and/or dRTA and antibodies to SS-A, regardless of whether subjective sicca symptoms are present or not, is hypothesised.</p>
  • Fall, Per-Arne, 1943- (författare)
  • Aspects of Parkinson's disease. Epidemiology, risk factors and ECT in advanced disease
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>The purpose was to investigate some aspects of epidemiology, risk factors and treatment with ECT in advanced Parkinson’s disease (PD).</p><p>In study I, we performed a descriptive epidemiologic population-based survey in the Central Health Care District in Östergötland in south-east Sweden, with a population of almost 150,000 inhabitants 1989. The case finding was accomplished in three ways: 1. Collection of all prescriptions for Parkinson’s disease. 2. Search in medical files. 3. Checking with all nursing homes in the area. The crude prevalence was found to be 115 per 100,000 inhabitants. When we used the European Standard Population as a tool for easy comparisons of PD prevalence between different areas and time periods 76 PD-cases per 100,000 inhabitants were found. The corresponding incidences were 11.0 (crude) and 7.9 (age standardised) per 100,000 person-years. Mean age at onset was 65.6. A low prevalence and a high age at onset suggested that e.g. environmental factors could influence the occurrence of PD, and the results implies that only few such factors were present in the investigated area.</p><p>The findings led to study II, a case-control study which investigated the possible impact of nutritional and environmental risk factors for idiopathic Parkinson’s disease (IP), including 113 cases and 263 control subjects. Dietary, drinking, and smoking habits, as well as previous occupation, were requested in a structured questionnaire. No increased risk was found for any of the nutrients. A reduced risk was found for coffee, wine, and spirits but also for broiled meat, smoked ham or meat, eggs, French loaf or white bread, and tomatoes. These findings could indicate an antioxidant effect. Frequency of preceding and present smoking was reduced in IP patients. Possible mechanisms are discussed. Various occupational groups and exposures were analysed and increased risks of IP in men were found for agricultural work, pesticide exposure, male carpenters, and in female cleaners.</p><p>In advanced PD there is a need for further therapeutic improvements, and electroconvulsive therapy (ECT) is one insufficiently explored and evaluated method. In study III ECT 16 non-depressed, nondemented PD patients with advanced disease were treated with ECT. In all patients an antiparkinsonian effect of ECT was seen, lasting between a few days and 18 months. Five patients, all with signs of blood brain barrier damage, developed transitory mental confusion after ECT. The results indicated that ECT could cause increased dopaminergic activity, which led us to study IV. Single photon emission computed tomography (SPECT) with the cocaine analogue [123I]-β-CIT was used in order to visualise dopaminergic neurones in the brain. Six patients with PD were examined before and after a series of ECT, and in three cases SPECT was also repeated after one year. The side-to-side difference in the radiotracer uptake was found to be significantly lower in striatum located contralaterally to the part of the body with most pronounced symptomatology. No significant change in uptake of [123I]-β-CIT was seen after ECT, although all patients improved and the most pronounced improvement was seen in patients with less advanced PD.</p><p>Study V points at two new positive observations with maintenance ECT (MECT). i.e. repeated ECT treatment of PD. One patient had either severe mental side effects on higher L-dopa doses or intolerable parkinsonian symptoms on lower doses. MECT implied marked improvement in parkinsonian symptoms without mental side effects. Another PD patient, who also had a mental depression, showed slight improvement of motor symptoms on a series of ECT. When treated with MECT further antiparkinsonian effects were seen.</p>
  • Ferrándiz, Rafael, 1953- (författare)
  • Allergenic characterization of the domestic mite <em>Dermatophagoides siboney</em>
  • 1997
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Allergic reactions to Pyroglyphid mites of the genus Dennatophagoides play an important role in the pathogenesis of asthma and other atopic diseases. Dermatophagoides siboney was described in Cuba in 1982. D. pteronyssinus and D. siboney are the most frequent mites in house dust collected from the homes of Cuban asthmatics, i.e., 100 and 85%, respectively.</p><p>The aims of the present studies were to investigate the prevalence of sensitization to D. siboney, Blomia tropicalis and other mite species in asthmatic patients from Cuba; to study the allergenic composition and to characterize the major allergens of D. siboney extracts; to investigate the crossreactivity between D. siboney and other mite allergens, and the relevance of patient selection for the determination of the biological activity of D. siboney and other domestic mites in the tropics.</p><p>Dermatophagoides siboney was found to be an important sensitizing agent among asthmatics in Cuba. Sensitization to B. tropicalis, D. pteronyssinus, D. farinae and A. siro, was also common as studied by skin and specific IgE tests. A combination of SPT with D. siboney, D. pteronyssinus and B. tropicalis diagnosed sensitization to mites in almost all mite sensitive patients. Thirteen allergenic proteins were identified in D. siboney extracts. Three components, 25, 14 and 30 kD, which bound to specific IgE strongly and frequently, were purified by affinity chromatography using crossreacting monoclonal antibodies to group 1; 2 and 3 allergens and named Der s 1, Der s 2 and Der s 3, respectively. TheN-terminal sequences of these allergens showed higher homology with D. jarinae and D. microceras than with D. pteronyssinus. The homology between group 2 allergens was higher than that of group 1 and 3 allergens.</p><p>A higher degree of crossreactivity was observed between allergens from D. siboney and D. farinae than betWeen D. siboney and D. pteronyssinus, B. tropicalis, A. siro, L. destructor or T. putrescentiae. Due to the crossreactivity, Cubans not exposed to D. farinae and Swedes not exposed to D. siboney and B. tropicalis, reacted to these mites. The individual allergens of D. siboney crossreacted more with those of D. farinae and D. microceras than with those of D. pteronyssinus. The 65, 62, 37 and 30 kD proteins, always inhibited by more than 50 % by the other mite species, were the main cause of the crossreactivity, The 80 kD protein was the less crossreactive allergen. Three MoAbs directed to Der s 1, one group crossreacting and two species specific, were produced. The crossreacting monoclonal antibody partly inhibited IgE binding to Der s 1 allergen. The results confmned the existence of crossreacting epitopes onDer s 1 but also indicate that this allergen has at least one species specific epitope.</p><p>The degree of reactivity to different mites seemed to be more related to patient selection criteria and extract potency rather than to exposure to a specific species.</p><p>Since D. siboney is common in dust from Cuban homes, it is probably present in other Caribbean countries and found to be an important sensitizer, it has been considered a potential candidate for the development of extracts for diagnosis and therapy of mite allergy. These studies contribute to the understanding of the characteristics of the allergens from this species and their relation to other mite allergens.</p>
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