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Biomedical subjects

L A Hanson

Publications and source records attributed to L A Hanson.

At least 37 records · Page 2Linked to original sources

Distribution of human kappa locus IGKV2-29 and IGKV2D-29 alleles in Swedish Caucasians and Hong Kong Chinese.

Polymorphism in the IGKV2-29 gene was shown to decrease the recombination frequency in B cells and to be important for immune responses to Haemophilus influenzae type b polysaccharide. By using the combination of PCR and restriction enzyme mapping, the distribution of IGKV2D-29 and IGKV2-29 gene alleles was estimated in two geographically and ethnically different groups. We found that V2D-29*01 homozygous individuals were most common in Swedish Caucasians (82%), but less common in the Chinese population of Hong Kong (28%). The homozygous V2D-29*02 genotype was found in 19% Chinese, but only in one Caucasian (1%). The frequency of the heterozygous V2D-29*01/V2D-29*02 genotype was also higher in the Chinese population (46%) compared with the Caucasians (7%). V2-29*01 homozygosity was more frequent among Caucasians (85%) than among Chinese (19%). In contrast, homozygous V2-29*02 individuals were over-represented in the Chinese population (18%), whereas only one was found among Caucasians (1%). Heterozygous V2-29*01/V2-29*02 individuals were also more common in the Chinese (63%) than the Caucasian (15%) population. Most Caucasians had the combination of V2D-29*01/V2D-29*01+V2-29*01/V2-29*01 (74%), while the most common genotype for Chinese was V2D-29*01/V2D-29*02+ V2-29*01/V2-29*02 (41%). Analysis of the association of V2D-29*02 and V2-29*02 alleles demonstrated a high degree of linkage, as for V2D-29*01 with V2-29*01. These data show a significant difference in the distribution of IGKV2D-29 and IGKV2-29 alleles among Swedish Caucasians and Hong Kong Chinese. This may help to explain differences in the occurrence of H. influenzae type b infection in the two populations. Evaluated methods for IGKV2D-29 and IGKV2-29 allele detection can be used for the screening allele polymorphisms in other particular patient groups.

Alleles↗

Titres of specific antibodies to poliovirus type 3 and tetanus toxoid in saliva and serum of children with recurrent upper respiratory tract infections.

A study of antibody levels (in saliva and blood) against common vaccine antigens was performed in a population of 32 children suffering from recurrent upper respiratory tract infections (URTI). None of the patients had primary or secondary immunodeficiency syndromes or other known predisposing factors for respiratory diseases. Titres of the isotype-specific antibodies immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) against two vaccine antigens--poliovirus type 3 (P3) and tetanus toxoid (TT), a viral antigen and a bacterial antigen, respectively--were measured in unstimulated saliva and serum, both in patients and in 24 healthy children (controls), by using a standard enzyme-linked immunosorbent assay (ELISA). In addition, levels of total IgA and avidity of IgA antibodies to both P3 and TT in saliva were evaluated. No difference was found between patients and controls as to levels of total IgA, or specific IgA and IgM antibodies against both P3 and TT in saliva. Furthermore, the avidity of salivary IgA antibodies against the two antigens did not differ between the two populations. However, the average concentrations of saliva-specific IgG antibodies to both the viral and the bacterial antigen were significantly lower (p <0.01 for P3 and p <0.05 for TT, respectively) in saliva of children with recurrent URTI, whereas no difference was found in serum for any immunoglobulin isotype determined compared with healthy individuals. The results of the present study provide suggestive evidence for the existence of subtle IgG-restricted defects in antibody responses at the mucosal level, but not at the serum level, in some children with undue susceptibility to URTI.

Adolescent↗

Different allelic frequencies of several cytokine genes in Hong Kong Chinese and Swedish Caucasians.

It has been shown that cytokine gene polymorphisms are important in the regulation of the level of cytokine production that may affect the development and extent of inflammatory diseases and transplant rejections. The frequency of the -308 TNFA, -383 TNFR1, -1087 IL10 and codon 25 TGFB1 alleles were analysed in two different ethnic groups: Chinese from Hong Kong and Caucasians from western Sweden. Significant differences in the occurrence of the analysed alleles were shown between the two populations. The most profound difference was found in the frequency of the A/A genotype at the -1087 position of IL10 gene (18% in Caucasians and 89% in Chinese, P < 0.0001, both for the genotype and allele frequencies) and less although statistically significant for other investigated genes. The noted differences in the frequency of functionally important alleles of cytokine genes may have consequences for the mode of appearance and outcome of certain diseases in individuals of different ethnicity.

Activin Receptors, Type I↗

IgG subclass profile of serum antigliadin antibodies and antibody-dependent cell-mediated cytotoxicity in young children with coeliac disease.

Recently, sera from children with active coeliac disease were found to efficiently induce antibody-dependent cell-mediated cytotoxicity (ADCC) of gliadin-coated cells. In the present study, the subclass profile of immunoglobulin (Ig)G antigliadin antibodies in sera from young children, with or without coeliac disease, was determined and related to the ADCC-mediating capacity of the same sera. In addition, IgG subclasses were selectively depleted from sera and the effect on ADCC-mediating was studied. Children with untreated coeliac disease had high antigliadin antibody activities of all four IgG subclasses. However, they had a particularly high proportion of IgG1 antigliadin antibodies (ratio IgG1/IgG) compared with healthy references or coeliac children in remission. In contrast, children who had high serum antigliadin antibody activity but no histological signs of enteropathy (disease references), showed significantly lower proportions of antigliadin antibodies of the IgG1 as well as the IgG3 subclass compared with healthy references or untreated coeliac children. Regression analysis showed that IgG1 and IgG3 antigliadin antibody activity correlated positively to ADCC-mediating capacity, and depletion of IgG1 from sera profoundly diminished ADCC. The results suggest that gliadin-specific antibodies of predominantly the IgG1 subclass mediate tissue-damaging immune reactions like ADCC, and may, thus, contribute to the disease process of coeliac disease.

Antibody Specificity↗

The Common vaccine adjuvant aluminum hydroxide up-regulates accessory properties of human monocytes via an interleukin-4-dependent mechanism.

Aluminum adjuvants are widely used in human vaccines based on their ability to enhance antibody production. However, the mechanisms underlying these effects remain unknown. In the present study we assessed the direct in vitro effect of aluminum hydroxide on human peripheral blood monocytes, specifically with regard to its impact on the phenotype and functional properties of this cell population. Our results revealed significant changes in the accessory properties of monocytes following short-term exposure of cultured cells to aluminum hydroxide. Thus, flow cytometry analyses showed an increase in the expression of major histocompatibility complex (MHC) class II, CD40, CD54, CD58, CD83, and CD86 molecules on the monocytes. In addition, many cells in the cultures containing aluminum hydroxide acquired typical dendritic morphology. Increased synthesis of interleukin-4 (IL-4) mRNA, but not gamma interferon mRNA, was also noted after exposure to aluminum hydroxide. The increase in cell surface expression of MHC class II did not occur in the presence of neutralizing IL-4 antibody or in cultures of highly purified monocytes or CD4-depleted mononuclear cells. Our findings suggest that aluminum hydroxide directly stimulates monocytes to produce proinflammatory cytokines activating T cells. Activated Th2 cells release IL-4, which in turn can induce an increase in the expression of MHC class II molecules on monocytes. The increase in the expression of antigen-presenting and costimulatory molecules leads to enhanced accessory functions of monocytes. These properties of aluminum hydroxide observed in vitro may explain its potent in vivo adjuvant effect.

Adjuvants, Immunologic↗

The use of polymerase chain reaction assay to diagnose proliferative gill disease in channel catfish (Ictalurus punctatus).

To assess the potential of a polymerase chain reaction (PCR) assay as a diagnostic tool in the detection of proliferative gill disease (PGD) in channel catfish (Ictalurus punctatus), PCR assays were compared with the traditional diagnostic methods of gill wet mounts and histology. A PCR assay using primers for Aurantiactinomyxon ictaluri, the actinospore associated with PGD, was performed with tissues from fish from commercial ponds. Using histology as the "gold standard," the sensitivity, specificity, and accuracy of the PCR assay were all >90%. In comparison, the wet mount examinations had a lower sensitivity and specificity. Using the chi-square test and a test for strength of association, there was a significant, strong association between results obtained by PCR and those obtained by the other 2 methods. These results demonstrate that the PCR assay is a good diagnostic tool for the detection of PGD.

Animals↗

Maternal essential fatty acid deficiency depresses serum leptin levels in suckling rat pups.

Dietary lipid quantity and quality have recently been shown to affect serum leptin levels in adult rats. Moreover, suckling pups from dams fed a high fat diet had increased serum leptin levels. The aim of the present study was to analyze the influence of essential fatty acid (EFA) deficiency on serum leptin levels in dams and their pups during the suckling period. For the last 10 days of gestation and throughout lactation, pregnant rats were fed a control or an EFA-deficient (EFAD) diet. The levels of leptin and EFA in the serum of the dams and pups were analyzed 1, 2, and 3 weeks after delivery. In parallel, serum levels of glucose and corticosterone were analyzed in the pups. Low serum leptin levels were found in the control lactating dams during the entire lactation period compared with the age-matched nonlactating animals. The leptin concentrations in the lactating dams fed the EFAD diet were lower compared with those fed the control diet. The serum leptin levels of suckling pups from dams on the EFAD diet were markedly decreased compared with controls (P < 0.05). The reduced serum leptin levels could not be explained by nutritional restriction as evaluated by serum levels of glucose and corticosterone. These results indicate the importance of the EFA composition of the maternal diet for serum leptin levels in both dams and pups. EFA deficiency in lactating dams may cause long-term effects on the pups through dysregulation of leptin and leptin-dependent functions. -- Korotkova, M., B. Gabrielsson, L. A. Hanson, and B. Strandvik. Maternal essential fatty acid deficiency depresses serum leptin levels in suckling rat pups. J. Lipid Res. 2001. 42: 359--365.

Aging↗

[The immune system of the hunter-gatherer meets poverty and excess].

The immune system is closely integrated with the neuroendocrine system, and infection-induced increases in cytokines such as IL-1, IL-6 and TNF have numerous effects on the central nervous system. These include stimulation of the hypothalamus-pituitary-adrenal (HPA) axis, as well as of leptin production. The increase in leptin causes loss of appetite, which may be deleterious for children who are living under conditions of poverty, have frequent infections and are often already undernourished. These cytokines may also be involved in problems of obesity, since they activate the HPA-axis and since TNF is produced by fat cells and can cause insulin resistance. The immune system originally developed for hunter-gatherers may not be well adapted to the pathology of poverty or that of excess.

Adaptation, Physiological↗

The mammary gland-infant intestine immunologic dyad.

The human infant has a very small immune system and needs the support of the mother with the transplacentally arrived IgG antibodies to protect tissues with inflammatogenic and energy-consuming defense. The mucous membranes, where most infections occur, need support via the specialized secretory IgA antibodies and the many other mucosal defense mechanisms provided via the mother's milk. This defense is not inflammatogenic and energy-consuming. We learn about additional defense factors in the milk, like the anti-secretory factor, which seems to protect against diarrhoea. The milk contains numerous growth factors and cytokines, like leptin, which may promote the development of the intestine as well as the immune system. Results are appearing giving interesting evidence for enhanced protection against infection also after the termination of breastfeeding. This may occur via the priming of the infant's immune system after uptake of anti-idiotypic antibodies and lymphocytes from the milk. A breastfeeding motivation study in a large Pakistani village resulted in a 50% decrease of diarrhoea and infant mortality. Deep interviews with the mothers and the traditional birth attendants suggested that even better results may be obtained.

Adjuvants, Immunologic↗

Antigen-specific regulation of CD1 expression in humans.

During the last decade the CD1 family of cell surface glycoproteins has been implicated in the presentation of nonpeptide antigens in man. Recent findings by our group indicate that CD1 molecules also can be involved in the presentation of certain bacterial proteins. However, CD1a, b, and c (group 1 CD1 molecules) are not present at significant levels on circulating monocytes unless their expression is induced by cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF). In this study we investigated the cell surface expression of CD1 molecules following the antigenic stimulation in vivo via immunization of healthy volunteers with tetanus toxoid vaccine and in vitro cell cultures using the same antigen. Both the in vivo and in vitro studies demonstrated clear up-regulation of the surface expression of CD1a, b, and c on monocytes as a result of antigenic stimulation with tetanus toxoid, supporting the idea that CD1 molecules participate in the presentation of this protein antigen in man. In vitro, antigen-triggered expression of these molecules was mediated by GM-CSF, since neutralization of this cytokine with specific antibody totally abrogated CD1a, b, and c expression. In contrast to the group 1 CD1 molecules, CD1d was found to be constitutively expressed on the majority of circulating monocytes and B lymphocytes prior to immunization. There was no effect of antigenic stimulation with tetanus toxoid on the cell surface expression of CD1d, suggesting major differences in regulation of the expression and function of the different CD1 molecules in humans. Altogether our results point to antigen-driven up-regulation of CD1a, b, and c expression on human monocytes that is mediated by GM-CSF and no effect on CD1d expression.

Adult↗

Tolerance and bystander suppression, with involvement of CD25-positive cells, is induced in rats receiving serum from ovalbumin-fed donors.

In the present study we have investigated if transfer of serum from rats fed ovalbumin (OVA) leads to specific tolerance and bystander suppression in recipient animals. Rats that received serum from OVA-fed donors had a lower delayed-type hypersensitivity reaction (DTH) both against OVA and the bystander antigen, human serum albumin (HSA), compared with recipients given serum from control-fed animals. The in vitro proliferation of OVA- and HSA-stimulated spleen cells and the serum immunoglobulin G (IgG) antibody levels against OVA and HSA were also lower in the animals that received serum from OVA-fed animals compared with the controls. There was no reduction of the immune response to HSA if the recipient animals, given serum from OVA-fed donors were immunized with OVA and HSA at separate sites. Depletion of CD25-positive cells from spleen suspensions from rats receiving serum from OVA-fed animals, resulted in a significant increase in proliferation of OVA-stimulated cells in vitro compared with the controls. Tolerogenic activity could be demonstrated, both in a fraction from serum containing structures smaller than 100 000 MW and a fraction with components larger than 100 000 MW, compared with size-related serum fractions obtained from control-fed animals. This implies that the tolerogenic activity could be mediated by more than one serum component. The tolerogenic activity was most prominent in animals receiving the larger size fraction with a more pronounced suppression of the DTH reaction and lower levels of IgG anti-OVA antibodies in serum compared with controls. A novel finding in the present study was that the transfer of serum, collected from rats fed OVA, led to a reduction of the immune response to a bystander antigen in the recipients. This suggests that the induced tolerance is at least partly due to suppression. The suppression could have been mediated by CD25-positive cells since removal of these cells resulted in an increased in vitro proliferation against OVA.

Animals↗

Interleukin-10 produced by the innate immune system masks in vitro evidence of acquired T-cell immunity to E. coli.

Bacteria trigger stimulation of antigen-specific, as well as innate, immune responses. Cytokines and other products of cells belonging to the innate immune system may interfere with the detection of acquired immunity to whole bacteria in vitro. Proliferation and cytokine production by human blood mononuclear cells in response to a whole UV-killed Escherichia coli was compared with the response to commonly used antigen preparations: purified protein derivative (PPD), Candida albicans and influenza proteins. E. coli induced a weaker proliferative response with later onset than did the other antigens, and production of interferon (IFN)-gamma comparable with that in response to C. albicans and influenza vaccine, but lower than that induced by PPD. Both proliferation and IFN-gamma production were abolished by removal of CD4 cells or blocking of HLA-D, but not CD1 antigen-presenting molecules. Purified lipopolysaccharide (LPS) induced neither proliferation nor IFN-gamma production. None of the antigen preparations stimulated interleukin (IL)-4 production but, in contrast to the other antigens, whole E. coli, as well as purified O6 LPS, induced large quantities of IL-10. IL-10 production was independent of CD4 cells or HLA-D molecules. Blocking of IL-10 by neutralizing antibodies increased both E. coli-induced proliferation and IFN-gamma production markedly. Conversely, the addition of whole E. coli or LPS to cultures stimulated with other antigens (C. albicans or Staphylococcus aureus) down-regulated proliferative and IFN-gamma responses, an effect which was at least partly IL-10 dependent. The results indicate a substantial T-cell memory to commensal E. coli, but suggest that the evidence of such memory, e.g. proliferation and IFN-gamma production, is effectively prevented by IL-10 and perhaps other factors produced by monocytes in response to bacteria. Thus, the innate immune responses must be taken into account when acquired immune responses to microbes are measured.

Antigens, CD1↗

Expression of CD1d in the duodenum of patients with cow's milk hypersensitivity.

CD1 cell surface glycoproteins represent a family of non-major histocompatibility complex (MHC) encoded antigen-presenting molecules. All members of the CD1 family appear to mediate the recognition of microbial or endogenous lipid and glycolipid antigens. The recognition of CD1d by a unique subset of natural killer (NK) T cells that leads to rapid production of large amounts of both type 1 and type 2 cytokines can be augmented by some synthetic glycolipids. Because of the proposed role of such CD1d-restricted T cells in immunoregulation, we hypothesized that CD1d molecules participate in mucosal immune responses in patients with gastrointestinal symptoms owing to food hypersensitivity. Patients of that category represent a heterogeneous group in which poorly defined immunological mechanisms are believed to contribute to disease pathogenesis. The expression of CD1 in duodenal biopsy samples from six patients with verified intolerance to cow's milk and six healthy controls was studied by immunoperoxidase staining of cryostat sections using a panel of mouse monoclonal antibodies (MoAbs) specific for CD1a, b, c, and d. Large numbers of CD1d positive cells were found in the lamina propria of all the patients, both during the symptomatic and the asymptomatic periods, whereas healthy controls were virtually devoid of CD1d expression in the duodenum. The localization of CD1d positive cells corresponded to areas where B cells, plasma cells and dendritic cells (DC) were present. A positive correlation was found between the numbers of CD1d(+) and CD19(+) cells in the lamina propria. In contrast to previous reports, no CD1d expression was found on the epithelial cells. Although less numerous than CD1d(+) the CD1c(+) cells were also present in all the patients and in five out of six controls. No staining for CD1a or CD1b was detected in the duodenal biopsy samples from any of the subjects. The exclusive presence of CD1d in the duodenal lamina propria of the patients with cow's milk hypersensitivity might suggest the participation of these molecules in the pathogenesis of allergic reactions to food.

Adult↗

Human lactoferrin and peptides derived from a surface-exposed helical region reduce experimental Escherichia coli urinary tract infection in mice.

Lactoferrin (LF) is a multifunctional immunoregulatory protein that has been associated with host defense at mucosal surfaces through its antibacterial properties. The antibacterial and anti-inflammatory properties of LF were further explored with an animal model of experimental urinary tract infection. Bovine LF (bLF), human LF (hLF), and synthetic peptide sequences based on the antibacterial region of hLF (amino acid residues 16 to 40 [HLD1] and 18 to 40 [HLD2]) were given orally to female mice 30 min after the instillation of 10(8) Escherichia coli bacteria into the urinary bladder. The control groups received phosphate-buffered saline or water. C3H/Tif mice were treated with hLF or bLF, and C3H/HeN mice were treated with bLF only. The numbers of bacteria in the kidneys and bladder of C3H/Tif and C3H/HeN mice were significantly reduced 24 h later by the LF treatments compared to the findings for the control group. The hLF-treated group showed the strongest reduction compared with the vehicle-treated-group (P values were 0.009 and 0.0001 for the kidneys and bladder, respectively). The urinary leukocyte response was diminished in the hLF-treated group. The hLF treatment also significantly reduced the urinary interleukin-6 (IL-6) levels at 2 h and the systemic IL-6 levels at 24 h after infection (P values were 0.04 and < 0.002, respectively). In the bLF-treated animals, no such strong anti-inflammatory effects were obtained. In another series of experiments, C3H/Tif mice perorally treated with HLD1 or HLD2 also showed reduced numbers of bacteria in the kidneys compared with the vehicle-treated mice, although the results were significantly different only for HLD2 (P < 0.01). Analysis of urine from hLF-fed C3H/Tif mice showed that hLF was excreted into the urinary tract at 2 h after feeding. Testing of the in vitro bactericidal activity of LF (1 mg/ml) or the peptides (0.1 mg/ml) in mouse urine against the E. coli bacteria revealed moderate killing only by HLD2. In conclusion, these results demonstrate for the first time that oral administration of hLF or peptides thereof is effective in reducing infection and inflammation at a remote site, the urinary tract, possibly through transfer of hLF or its peptides to the site of infection via renal secretion. The antibacterial mechanism is suggested to involve bactericidal capacities of LF, fragments thereof, or its peptides.

Amino Acid Sequence↗

The mother-offspring dyad and the immune system.

UNLABELLED: A. The mother and the fetus. The mother's immune system reacts against the fetus and there is therefore a risk of destruction of or damage to the fetus. We are now beginning to understand some of the mechanisms that protect the fetus, but, when these are defective, intrauterine growth retardation or abortions may ensue. However, the cytokines of this maternal immune response to the fetus also monitor different phases of pregnancy, starting with effects on the ovarium and involving preparation of the decidua for the implantation of the fertilized egg, the growth of the trophoblasts, the production of hormones important for the pregnancy and finally of the prostaglandins that induce delivery. B. The mother and the child. Human milk contains anti-idiotypic antibodies which after transfer to the offspring are capable of enhancing antibody responses. Human milk contains numerous leucocytes especially during early lactation. There is increasing evidence that milk lymphocytes are taken up by the breastfed infant, which seems to have become tolerant to maternal HLA. Breastfeeding mothers are therefore good donors of renal transplants to their breastfed offspring in adult age, too. CONCLUSION: It is suggested that the milk lymphocytes may be taken up by the offspring and that immunological information is thereby carried over from the mother. This mechanism may explain why breastfeeding seems to confer enhanced protection against infections also some years after the termination of breastfeeding.

Antibodies, Anti-Idiotypic↗

Nefazodone attenuates the stress-induced facilitation of wet dog shaking behaviour but not the facilitation of sexual behaviour in female rats.

The effects of chronic stress both alone and in combination with the antidepressant, nefazodone, which possesses antagonistic activity at the 5-HT2A receptor, were examined on the 5-HT2A receptor-mediated behaviour, wet dog shaking and sexual behaviour. Ovariectomized female rats received either a chronic stressor or no stress for 30 days, and half of each group received concurrent nefazodone treatment (100 mg/kg/day). Following treatment with either estrogen, or estrogen combined with progesterone, sexual behaviour and wet dog shaking were recorded. Chronic stress alone was found to facilitate sexual behaviour and increase wet dog shaking, while nefazodone administration alone was without effect. Furthermore, nefazodone completely attenuated the stress-induced facilitation of wet dog shaking, but not sexual behaviour.

Animals↗

Channel catfish virus gene 50 encodes a secreted, mucin-like glycoprotein.

Cells infected with the wild-type (WT) strain of channel catfish virus (CCV) secreted a glycoprotein with an apparent molecular mass (MM) superior to 200 kDa into the culture medium. This protein, designated gp250, was the sole viral glycoprotein detected in the culture medium after [3H]mannose labeling of the infected cells. When cells were infected with the attenuated V60 strain, a glycoprotein of 135 kDa (designated gp135) was detected instead of gp250. Because WT gene 50 is predicted to encode a secreted, mucin-type glycoprotein, we expressed this gene transiently and detected a glycoprotein of the same apparent MM as gp250 in the culture medium of transfected catfish cells. The increased mobility in SDS-PAGE of the secreted V60 glycoprotein correlated with the presence of a major deletion in V60 gene 50. Therefore, we concluded that gp250 in the WT and gp135 in the V60 strains are both likely encoded by gene 50. An important shift in the relative mobility of gp250 in SDS-PAGE was observed after tunicamycin treatment of infected cells labeled with [3H]glucosamine, confirming the presence of N-linked sugars on gp250. We observed variations in the size of PCR products derived from gene 50 amplification in three different field isolates. Such genetic variations are a characteristic feature of mucin genes and are linked to crossing-over events between internal repeated sequences, such as those present in gene 50.

Animals↗