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Biomedical subjects

L Lundberg

Publications and source records attributed to L Lundberg.

At least 37 records · Page 2Linked to original sources

Immunologically induced purulent anterior segment inflammation of the guinea pig eye.

A single conjunctival application of ovalbumin to inbred guinea pigs (IMM/S 209) immunized with the same antigen in Freund's complete adjuvant provoked an acute purulent inflammation of the anterior segment of the eyes with a duration of up to 1 week. Intense conjunctival injection and chemosis were followed by a purulent discharge. A corneal haze was observed regularly, and a considerable proportion of the animals developed a pronounced pannus and corneal ulcers. Tear fluid cytology revealed a rapid increase in cell concentration, from the normal level (less than 10(8)/l) to greater than 10(11)/l. Seventy to 95% of the cells were polymorphonuclear leukocytes. Histological examination revealed an acute inflammatory reaction which radiated from the conjunctival fornices to the entire anterior segments of the eyes. The process was characterized by an intense oedema, vasodilation and perivascular aggregations of polymorphonuclear leukocytes, and to a lesser extent eosinophilic granulocytes which characteristically infiltrated and penetrated the epithelial layers. Neovascularization could be observed early after challenge in the stroma of all parts of the outer eye. Ulcerations of the conjunctival and corneal epithelia were observed frequently. After a number of reiterations of the antigenic challenge, a marked infiltration with lymphocytes and basophils/mast cells was observed, and significant scarring of the conjunctival mucosa developed. In several animals, a slight, but significant co-reaction of the contra-lateral, non-challenged eye was observed.

Acute Disease↗

Genetic control of eosinophilia in guinea pig strains inbred for high or low bronchial allergic reactivity. 2. A genetic study of spontaneous and immunization-induced eosinophilia.

In 4 inbred strains of guinea pig the tendency to develop peripheral high-eosinophilia was shown to be genetically controlled. The development of eosinophilia with age and following immunization was examined in high- and low-eosinophilic parental strains, in F1-hybrids and in backcross offspring. The results show that probably only one or a very few segregating genes control eosinophilia, and they also indicate that different genes are involved in the determination of spontaneous (age-related) and immunization-induced eosinophilia.

Animals↗

Histamine-induced bronchoconstriction in conscious guinea pigs measured by strain-gauge transduction. A new method.

A new objective method for measuring histaminedihydrochloride-induced bronchoconstriction in conscious guinea pigs has been developed. The aim of the present work was to investigate whether identical results could be obtained when the clinical observation of conscious guinea pigs with symptoms of respiratory distress (bronchoconstriction) was compared to an objective measuring technique of this parameter. An evaluation of the repeatability of the method was made and the respiration frequence (fR) and histaminedihydrochloride challenge concentration were compared to see whether there was a correlation between the two. Consequently, an apparatus was built that allowed simultaneous recording of breathing pattern and clinical observation of the animal being challenged. The breathing pattern was recorded by a strain-gauge transducer, connected to a measuring bridge, and the curves obtained on a jet ink x-y writer were used for calculating changes in duration of expiratory phase (Te) and fR. During the attacks of histaminedihydrochloride-induced bronchoconstriction a significantly prolonged Te could be calculated from the respiration curves. A high degree of agreement was found between this objective measure and clinically observed respiratory distress. The repeatability of the method was comparable to that of corresponding methods used for histaminedihydrochloride challenge in man. No obvious correlation was found between changes in fR and histaminedihydrochloride challenge concentration.

Animals↗

Circulatory basophilia in guinea pigs with delayed-type hypersensitivity. Topical antigenic provocation induces circulatory basophilia.

Circulatory basophilia could be induced in inbred guinea pigs systematically immunized with ovalbumin and consequently provoked repeatedly with dissolved ovalbumin applied onto the mucosa of the nares or the outer eye. The degree of the increase in circulatory basophil granulocytes depended on the adjuvant used and was significantly more pronounced after immunization with Freund's complete adjuvant than with alhydrogel (Al(OH)3). The degree of basophilia was also dependent on the animal strain, but different in two strains selected for high-asthma trait.

Adjuvants, Immunologic↗

Genetic control of eosinophilia in guinea pig strains inbred for high or low bronchial allergic reactivity.

Development of eosinophilia was studied in four strains of guinea pigs (gp), selectively bred for either high or low respiratory anaphylactic reactivity. One high-asthma strain (IMM/S 209) and one low-asthma strain (IMM/R 203) developed spontaneous high blood eosinophilia. The 2 other gp strains - one high-asthma strain (IMM/S 740) and one low-asthma strain (IMM/R 201-16) - maintained normal low levels of eosinophilic granulocytes (eos). The levels of eos in various tissues showed similar differences between the gp strains. Following immunization with ovalbumin/Al(OH)3 the levels of blood eos increased significantly only in gp of strain 209. The blood eos levels in gp of all 4 strains decreased significantly following immunization with ovalbumin in Freund's complete adjuvant (FCA).

Aging↗

Congenital malformations and structural developmental anomalies in groups at high risk for psychosis.

OBJECTIVE: Early somatic developmental anomalies may be one expression of a genetic influence toward psychosis. The purpose of this study was to investigate whether higher rates of early developmental anomalies are associated with heightened genetic risk for psychosis. METHOD: Rates of congenital malformations and minor structural developmental anomalies were prospectively investigated in 84 high-risk offspring of women with histories of psychosis of nonorganic origin (schizophrenic, schizoaffective, affective, and other psychoses) and in 100 offspring of demographically similar control women with no history of psychosis. Data were collected by means of multiple physical examinations through the first 3-4 years of the offspring's lives. RESULTS: The rates of total congenital malformations were high, but the great majority of these malformations in both the index group and the control group represented minor physical aberrations. Rates of congenital malformations in the offspring of the index women (or any specific diagnostic subgroup of these women) were not different from those in the offspring of the control women. CONCLUSIONS: The inferred genetic risk for psychosis does not appear to be associated with greater rates of early somatic developmental anomalies, suggesting that early developmental anomalies do not represent an expression of genetic influence toward psychosis.

Comorbidity↗

Granulocyte elastase, beta-thromboglobulin, and C3d during acetate or bicarbonate hemodialysis with Hemophan compared to a cellulose acetate membrane.

Twenty-two patients were dialysed in a cross-over design using Hemophan or cellulose acetate membranes. The dialysate buffer was acetate (n = 12) or bicarbonate (n = 10). Blood was sampled at 0, 15, 60 and 180 min and mean values were adjusted for changes in total protein in each sample. At 15 min during dialysis a decrease in leukocytes and platelets occurred with both membranes, irrespective of the buffer (Wilcoxon, p less than 0.006). During dialysis, increases were found in granulocyte elastase inhibitor complex (E- alpha 1-PI), beta-thromboglobulin and C3d. beta 2-microglobulin was not significantly changed in blood after dialysis with Hemophan or cellulose acetate membranes with bicarbonate buffer. Side effects were more pronounced at 180 min during dialysis with bicarbonate in patients using cellulose acetate than with Hemophan (p = 0.021, n = 8). Hemophan seemed to be more favourable than cellulose acetate membranes in regard to leukopenia and E- alpha 1-PI. The dialysate buffer may also alter membrane biocompatibility.

Biocompatible Materials↗

Allergen-containing immune complexes used for immunotherapy of allergic asthma. II. IgE and IgG immune response during and after hyposensitization of sensitized guinea pigs.

In a previous study guinea pigs inbred for their ability to develop respiratory anaphylaxis to experimental antigens have been used for comparison of different forms of immunotherapy (IT). Passive, active and combined (immune complexes prepared from antigen and specific IgG) IT was compared with placebo. In the present study methods were evaluated for determination of the allergen-specific IgE and IgG. IgE was determined by the passive cutaneous anaphylactic test (PCA) and the variability of this test on different strains of the recipient guinea pig was investigated. The same strain as used for the IT study was found to produce the most potent response. Radioimmunometric assays (RIA) were developed and validated for determination of specific IgG1 and IgG2. The IgE and IgG immune response in animals from the IT study were then evaluated by means of PCA and RIA. Animals from all four treatment groups were sensitized during the first part of the IT study, and responded with a marked IgE synthesis which later stabilized on a more moderate level. In spite of notably reduced symptoms in groups treated with active and combined IT, no difference in the IgE level was found between the four groups. In contrast to IgE, mean group titers of IgG1 and IgG2 in the groups receiving active or combined IT rose drastically during the first part of therapy and closely paralleled the clinical response during the rest of the study period. However, in the individual animals, no correlations were found between immune response and clinical symptoms. Thus, the strong IgG response during immunotherapy may not be causally related to the outcome of treatment.

Animals↗

Reactivity of lymphoid cells isolated from the tracheobroncheal lymph nodes of two guinea-pig strains with high or low susceptibility to respiratory anaphylaxis.

The mechanisms underlying the different sensitivity to respiratory anaphylaxis were studied in two inbred strains of guinea pigs with high (IMM/S) or low (IMM/R) sensitivity to ovalbumin (OA) aerosol-induced respiratory anaphylaxis. Guinea pigs were immunized with OA in Freund's complete adjuvant and lymphocyte stimulation tests were done with cells from the tracheobroncheal lymph nodes (TBL) draining the airways, from peripheral blood lymphocytes and from the axillary and inguinal lymph nodes. The TBL of the IMM/R strain had a significantly lower response than those of the IMM/S strain. This selectively low response, which was not antigen specific, could be increased by cyclophosphamide pretreatment. The high TBL response in the IMM/S strain was decreased by OA inhalations to the level of the IMM/R strain. OA inhalations decreased the IgE response in the IMM/S but not the IMM/R strain. Different interpretations of these findings are discussed, with emphasis on the possibility that an inherent suppressor cell population in the TBL are involved.

Anaphylaxis↗

Cystein 402 of HIV gp 120 is essential for CD4-binding and resistance of gp 120 to intracellular degradation.

A DNA fragment encoding the CD4-binding region of human immunodeficiency virus type 1 (HIV) gp 120 was excised from an SV40-based expression vector containing gp 160, and subcloned into phage M13 for site-directed mutagenesis. Mutant vectors were constructed and CV-1 cells were transfected with constructs, where Cys402 was substituted for a serine, and metabolically labelled with [3H]-N-acetylglucosamine (GlcN). Radioimmunoprecipitation with an hyperimmunserum, specific for gp 120/gp 160, and subsequent SDS-polyacrylamide gel electrophoresis demonstrated presence of gp 160, whereas gp 120 was replaced by [3H]-GlcN-labelled material, migrating as a diffuse band corresponding to 80-105k, suggesting increased sensitivity of mutant env gene products to proteolysis after cleavage to gp 120. Wild type gp 120 and gp 160 bound to CD4, whereas neither gp 160 nor gp 120 from mutant-transfected cell lysates did bind to CD4. Altogether the results indicated that Cys402, probably by participating in a disulfide bridge, is essential for (i) the CD4-binding ability of env gene products and for (ii) the physical stability of gp 120.

Amino Acid Sequence↗

Allergen-containing immune complexes used for immunotherapy of allergic asthma. Preparation of complexes and evaluation of their clinical performance in guinea pigs.

Guinea pigs inbred for their ability to develop respiratory anaphylaxis to experimental antigens have been used for comparison of different forms of immunotherapy (IT). Passive, active and combined (immune complexes between antigen and specific IgG) IT were compared with placebo. The bronchial reactivity of the animals to the antigen was monitored regularly before, during (35 weeks) and after IT (20 weeks). Animals treated with passive IT did not improve clinically. Active and combined IT abolished most symptoms within 7 weeks of treatment. During the post-treatment period, animals from both groups surprisingly recovered their original sensitivity to inhalation of the antigen.

Allergens↗

A prospective study of psychosocial background factors associated with congenital malformations.

Women's life situation and experiences during pregnancy were prospectively studied in relationship to the development of congenital malformations (CMs) in their offspring, within samples of 84 offspring of pregnant index women with a history of nonorganic psychosis and 100 offspring of pregnant control women. Within both samples, offspring CMs were related to more problematic maternal life situations during pregnancy, the common denominator in these problems across samples being difficulties associated with the husband. Little relationship was found between CMs and the woman's own attitude toward the pregnancy or her mental condition during pregnancy. In both groups, total life situational problems and distress were more strongly related to the development of very minor CMs (termed "variants") than to the major, classical CMs.

Congenital Abnormalities↗

Cis- and trans-acting elements responsible for the cell-specific expression of the human alpha 1-antitrypsin gene.

The 5' flanking region of the human alpha 1-antitrypsin (alpha 1-AT) gene contains cis-acting signals for liver-specific expression and, when fused to a reporter gene, is able to drive the expression of this gene specifically in liver cells. Here we report the results of a functional dissection of the alpha 1-AT regulatory region. The expression of the bacterial chloramphenicol-transacetylase (CAT) gene, fused to a set of alpha 1-AT 5' flanking regions shortened by progressive deletions or mutated by base pair substitutions, has been compared by transfection in HepG2 (hepatocyte) and HeLa (non-hepatocyte) human cell lines. A minimal tissue-specific element has been identified between the nucleotides -137 and -37 (from the transcriptional start site). This DNA segment activates the heterologous SV40 promoter in hepatoma cell lines but not in HeLa cells. This element contains at least two regions referred to as the A (-125/-100) and B (-84/-70) domains, both essential for transcription. There are at least two other regulatory domains located upstream of the 'minimal element'; the most active of these is located between positions -261 and -210 from the cap site. These upstream elements activate the heterologous SV40 early promoter both in hepatoma cell lines and in HeLa cells. Upon fractionation of rat liver nuclear extracts two proteins have been identified, alpha 1TF-A and alpha 1TF-B, which bind specifically to the A and B domains respectively. Transcriptionally inactive A and B domain mutants are not able to bind these proteins.

Base Sequence↗

Experimental allergic conjunctivitis in inbred guinea pig strains with high respectively low bronchial allergic reactivity.

Inbred guinea pigs selected for high (IMM/S) respectively low (IMM/R) responsiveness to ovalbumin (OA) as measured by induced respiratory anaphylaxis, were investigated for atopic immune responses of their conjunctival mucosa. IMM/S animals sensitized either by inhalation of OA, or by instillation of antigen into the conjunctival sac, developed regularly an acute ocular inflammatory response to topical (conjunctival) challenge with the allergen. A minimum of 1 microgram OA dropped repeatedly into the conjunctival sac was enough for both ocular and systemic sensitization of the animals, but the minimal dose of effective challenge was considerably higher. In IMM/R animals, ocular hypersensitivity was not achieved by inhalation of OA, but after topical administration of the antigen some of the IMM/R strains could be challenged to ocular anaphylactic responses of the same intensity as observed in IMM/S animals. The conjunctivae of both IMM/S and IMM/R animals could be sensitized passively by intraperitoneal injection of guinea pig sera containing homocytotropic antibodies to OA, but topical administration of such sera had no effect.

Administration, Inhalation↗