Biomedical subjects

L A Hanson

Publications and source records attributed to L A Hanson.

At least 55 records · Page 3Linked to original sources

PubMed1999

Natural selection of the Pol gene of bovine immunodeficiency virus.

Genetic variability is a salient feature of lentiviruses, contributing to the pathogenesis of these viruses by enabling them to persist in the host and to resist anti-retroviral treatment. Bovine immunodeficiency virus (BIV), a lentivirus of unknown pathology, infects cattle in the United States and worldwide. Genetic diversity of BIV that is associated with naturally infected cattle is not well studied. We examined the genetic diversity and natural selection of a segment of the BIV pol gene amplified from the leukocyte DNA of naturally infected cattle. A portion of the reverse transcriptase domain (183 bp) of the pol region was targeted for amplification by PCR. PCR products were sequenced directly and aligned. When compared to the sequences of BIV R29-127, a molecular clone of the original BIV R29 isolate, all isolates were greater than 91% identical in nucleotide sequences and 77% identical in amino acid sequences. Pol genotypes were polymorphic at 14% of the nucleotide sites. The ratio of nonsynonymous to synonymous nucleotide substitutions (relative to the number of respective sites, Ka/Ks) was 0.16, indicating that this region of the BIV genome, like that of HIV-1, is subject to purifying selection. Based on the McDonald-Kreitman analysis, this region also was under positive Darwinian selection as HIV-1 and BIV diverged from a common progenitor. Phylogenetic analysis revealed that genotypes were geographically distinct, possibly indicating a common source of infection for animals within a herd.

Amino Acid Sequence↗

PubMed1999

Neonatal colonization of rats induces immunological tolerance to bacterial antigens.

We wanted to investigate the immunological events occurring in rats intestinally colonized from birth (neonatally) or at adult age with an ovalbumin (OVA)-producing Escherichia coli O6K13 strain, carrying type 1 pili. The neonatally colonized animals responded with lower delayed type hypersensitivity (DTH) against OVA and lower levels of IgG antibodies against OVA, O6 lipopolysaccharide (LPS) and type 1 pili compared to age-matched controls. The IgG antibody response against the bystander antigen, human serum albumin (HSA), was lower in the neonatally colonized animals than in the controls co-immunized with HSA and E. coli, indicating a release of suppressive factors induced by the bacterial antigens. The adult colonized animals showed an increased DTH and antibody response against OVA after immunization. They also had high pre-immunization levels of IgG anti-O6 LPS antibodies compared to controls. However, the relative increase in IgG anti-O6 LPS antibody levels after the immunization with dead E. coli was much lower in the adult colonized animals. The present results suggest that neonatal animals develop tolerance against antigen on bacterial colonizers of the intestine. In addition, this tolerance contains components of suppression.

Animals↗

PubMed1999

An IL-2-toxin, DAB389IL-2, inhibits delayed-type hypersensitivity but enhances IgE antibody production.

BACKGROUND: Expression of high-affinity IL-2 receptor (IL-2R) on T lymphocytes, key cells in chronic inflammation, is a T-cell activation marker. OBJECTIVE: We sought to evaluate the effect of the fusion protein DAB389IL-2, which kills cells bearing IL-2R, on delayed-type hypersensitivity and antibody production in Brown Norway rats sensitized with trimellitic anhydride (TMA). METHODS: DAB389IL-2 (25 micrograms/kg/day) or placebo was administered intraperitoneally for 8 days over the period of sensitization, starting 2 days before sensitization. RESULTS: The administration of DAB389IL-2 resulted in a one-third reduction in the number of IL-2R-bearing cells and significant weight loss of animals. Delayed-type hypersensitivity, evaluated at 5 weeks after sensitization, was significantly inhibited by treatment with DAB389IL-2. In contrast, production of IgE anti-TMA antibodies after sensitization was increased by treatment with DAB389IL-2. DAB389IL-2 affected neither IgG anti-TMA antibody nor total IgE levels. CONCLUSION: These data imply that systemic administration of DAB389IL-2 in Brown Norway rats influences cells that have regulatory effects on the immune system, resulting in a switch from a TH1 to a TH2 type of immune response.

Allergens↗

PubMed1999

The influence of corticosterone on serotonergic stereotypy and sexual behavior in the female rat.

The effects of adrenalectomy and chronic corticosterone treatment on sexual behavior in the ovariectomized female rat were investigated. The serotonergic type 2A (5-HT2A) receptor-mediated behavior 'wet dog shakes' (WDS) was measured concurrently. In Experiment 1, adrenalectomy reduced the frequency of WDS following the administration of the 5-HT(2A/2C) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) but had no effect on spontaneous WDS. In Experiment 2, chronic corticosterone treatment increased DOI-induced WDS in both adrenalectomized and sham-adrenalectomized rats. In Experiment 3, adrenalectomized and sham-adrenalectomized rats were compared on measures of spontaneous WDS and sexual behavior following the administration of estrogen alone, or estrogen in combination with progesterone. Chronic corticosterone and acute progesterone administration increased WDS and facilitated sexual receptivity and proceptivity, while adrenalectomy decreased WDS, facilitated sexual receptivity and inhibited proceptivity. These findings suggest that the behavioral effects seen following hypothalamic-pituitary-adrenal (HPA) axis disruption may, in part, be mediated by altered 5-HT2A receptor responsivity.

Adrenalectomy↗

PubMed1999

Active suppression in orally tolerized rats coincides with in situ transforming growth factor-beta (TGF-beta) expression in the draining lymph nodes.

Adult rats were fed pellets containing ovalbumin (OvA) during 4 weeks, and were 2 weeks thereafter immunized subcutaneously with a mixture of OvA and human serum albumin (HSA) in Freund's complete adjuvant (day 0). As a result of the immunization, the draining lymph nodes of the nontolerized (control) rats were heavily enlarged from day 10 to day 18; however, this size increase was absent in the OvA-fed rats. This manifestation of active suppression in the tolerized rats was preceded by the appearance of scattered CD4+ TGF-beta-expressing T cells in the T cell area of their lymph nodes (days 5-8); correspondingly, the levels of TGF-beta mRNA in the nodes were elevated in the tolerant rats compared with the control rats. The anti-OvA antibody levels in sera from the rats revealed that there was an initial B cell priming in the OvA-fed group, with levels higher than in the control group during the first week. Thereafter, suppression governed the response, and from day 10 onwards the anti-OvA levels were considerably lower than in the controls. When other groups of animals were pretreated with neutralizing anti-TGF-beta antibodies 1 day before the immunization, the anti-OvA response of the OvA-fed rats was restored to the levels of the control group, demonstrating the importance of TGF-beta in the maintenance of suppression. In conclusion, we demonstrate that TGF-beta-producing cells appear in the draining lymph nodes shortly after immunization in rats made orally tolerant using a relatively high-dose feeding regime; these cells are probably responsible for the down-regulation of the immune response observed in the OvA-fed rats.

Administration, Oral↗

PubMed1999

Lactobacilli from human gastrointestinal mucosa are strong stimulators of IL-12 production.

Interaction of macrophages with bacteria is a stimulus for production of cytokines such as IL-10 and IL-12. IL-12 stimulates T cell and natural killer (NK) cell cytotoxicity and interferon-gamma (IFN-gamma) production. IL-10 opposes the T cell-stimulating action of IL-12, decreases the release of proinflammatory cytokines from macrophages, and stimulates B cells. We have studied the capacity of human intestinal isolates from the three Lactobacillus species dominating on the human gastrointestinal mucosa, L. plantarum, L. rhamnosus and L. paracasei ssp. paracasei, to induce production of IL-10 and IL-12 from human blood mononuclear cells, or monocytes. Whole killed lactobacilli were potent stimulators of IL-12 over a wide range of bacterial concentrations. Lactobacillus paracasei gave the highest levels of IL-12 (1.5 ng/ml in response to 5 x 106 bacteria/ml), roughly 10 times more than obtained by stimulation with L. rhamnosus or L. plantarum. Escherichia coli induced on average < 50 pg/ml of IL-12 regardless of the bacterial concentration used. The secretion of free p40 subunit IL-12 followed the same pattern as the secretion of p70 (bioactive IL-12) with regard to the efficiency of different bacteria as stimulators. Escherichia coli was the most efficient trigger of IL-10 production, inducing 0.5 ng/ml IL-10 after stimulation with 5 x 106 bacteria/ml. Lactobacillus rhamnosus induced the highest levels of IL-10 among the lactobacilli (0.5 ng/ml) compared with 0.1 ng/ml evoked by L. plantarum or L. paracasei, but 10 times more bacteria were required for optimal stimulation than with E. coli. When neutralizing anti-IL-10 antibodies were added to the cultures, the IL-12-inducing capacity of L. rhamnosus was increased markedly, while that of E. coli remained low. The results show that mucosa-associated lactobacilli can be potent stimulators of IL-12, and thus potentially of cell-mediated immunity, if they pass over the gut epithelial barrier and interact with cells of the gut immune system.

Cells, Cultured↗

PubMed1999

Immunomodulatory effects of Lactobacillus plantarum colonizing the intestine of gnotobiotic rats.

We have studied the effect of the probiotic strain Lactobacillus plantarum 299v on the immune functions of gnotobiotic rats. One group of germ-free rats was colonized with the type 1-fimbriated Escherichia coli O6:K13:H1 and another group with the same E. coli strain together with L. plantarum 299v. One and 5 weeks after colonization, bacterial numbers were determined in the contents of the small intestine, caecum and mesenteric lymph nodes. Small intestinal sections were examined for CD8+, CD4+, CD25+ (IL-2R alpha-chain), IgA+ and MHC class II+ cells and mitogen-induced spleen cell proliferation was determined. Immunoglobulin levels and E. coli-specific antibodies were measured in serum. Rats given L. plantarum in addition to E. coli showed lower counts of E. coli in the small intestine and caecum 1 week after colonization compared with the group colonized with E. coli alone, but similar levels after 5 weeks. Rats colonized with L. plantarum + E. coli had significantly higher total serum IgA levels and marginally higher IgM and IgA antibody levels against E. coli than those colonized with E. coli alone. They also showed a significantly increased density of CD25+ cells in the lamina propria and displayed a decreased proliferative spleen cell response after stimulation with concanavalin A or E. coli 1 week after colonization. The results indicate that L. plantarum colonization competes with E. coli for intestinal colonization and can influence intestinal and systemic immunity.

Animals↗

PubMed1999

Participation of CD1 molecules in the presentation of bacterial protein antigens in humans.

Human CD1 molecules, expressed on the surface of professional antigen-presenting cells (including dendritic cells, Langerhans' cells, B cells and activated monocytes) are structurally homologous to major histocompatibility complex (MHC) class I and class II molecules. CD1b and CD1c have been shown to present nonpeptide bacterial antigens to T cells. We hypothesized that CD1 molecules may also be involved in the presentation of bacterial protein antigens. Human peripheral blood mononuclear cells (PBMC) were exposed to two medically important proteins, tetanus toxoid (TT) and purified protein derivative (PPD), with and without murine monoclonal antibodies (MoAbs) specific for CD1a, CD1b and CD1c. All the MoAbs substantially inhibited the proliferative responses of PBMC to TT and PPD. Simultaneous interaction of CD1 and MHC class II molecules was even more inhibitory to these antigen-specific proliferative responses. In contrast, neither mixed lymphocyte reaction nor superantigen and mitogenic responses were affected by CD1-specific antibodies, indicating a certain restriction pattern in antigen presentation. Our findings suggest that, besides MHC class I and II molecules, there is a family of nonpolymorphic cell surface molecules that is able to present certain bacterial protein antigens to T cells.

Antibodies, Monoclonal↗

PubMed1999

Antibodies given orally in the neonatal period can affect the immune response for two generations: evidence for active maternal influence on the newborn's immune system.

Two day old Wistar rats were tube fed with 1 or 10 micrograms of a mouse IgG1 monoclonal anti-idiotypic (a-Id) antibody that was directed against an anti-Escherichia coli-K13 capsular polysaccharide antibody. A control group was given 10 micrograms of an unrelated control antibody. Six weeks after the administration of antibodies, the rats were intestinally colonised with an ovalbumin (OVA)-producing E. coli O6K13 strain. At 8 weeks of age, the male rats (first generation) and the offsprings of the female rats (second generation), were parenterally immunised with OVA and dead wild type E. coli O6K13, and the immune response was followed. In the rats of the first generation, there were no major differences between the groups in the immune response to the bacterium. However, the offspring of the neonatally a-Id administered rats had a profoundly affected immune response to the idiotypically connected antigen K13, but also to other antigens on the bacteria. Thus, a-Id treatment in the first generation gave, in the second generation, a greatly enhanced serum antibody response to the spatially related antigens OVA and O6 LPS, as well as to the idiotypically connected antigen K13. Concurrently, the in vitro spleen cell proliferative response to both OVA and the wild type bacterium was lowered. Overall, greater effects were seen with the higher dose of a-Id. In conclusion, our results demonstrate that by giving monoclonal antibodies idiotypically connected to a single bacterial component to neonatal rats, one profoundly influence the immune response also to other-spatially related-bacterial antigens in their offsprings.

Administration, Oral↗

PubMed1999

The impact of climate on the prevalence of respiratory tract infections in early childhood in Lahore, Pakistan.

BACKGROUND: Respiratory tract infections are a major health problem in developing countries. The aim of this study was to analyse the impact of the climate on the prevalence of upper respiratory tract infection (URTI) and lower respiratory tract infection (LRTI) in four socioeconomically different groups in a developing country. METHODS: A prospective cohort study was conducted among children in four socioeconomically different groups in Lahore, Pakistan. Monthly observations were made on 1476 infants born during 1984-1987 and followed for 24 months. Prevalence of URTI and LRTI was analysed according to age, area of living, family size, time of birth, the season of the year and climate variables such as rain, temperature and humidity. RESULTS: Low monthly average minimum day temperature was associated with high prevalence of URTI and LRTI. For LRTI the impact of temperature was larger for boys, children living in larger families and children living in the poorer areas. This pattern was not seen for URTI. A peak in prevalence for LRTI was shown at 5-6 months of age for LRTI and at 10-12 months of age for URTI. CONCLUSIONS: Temperature is related to prevalence of URTI and LRTI in a developing society. The effect of temperature on health varies between different subgroups. These effects should be considered in planning health actions to prevent respiratory tract infections.

Age Distribution↗

PubMed1999

Human milk and host defence: immediate and long-term effects.

Convincing studies demonstrate significant protection during breastfeeding against diarrhoea, respiratory tract infections, otitis media, bacteraemia, bacterial meningitis, botulism, urinary tract infections and necrotizing enterocolitis. There is also good evidence for enhanced protection for years after the termination of breastfeeding against Haemophilus influenzae type b infections, otitis media, diarrhoea, respiratory tract infections and wheezing bronchitis. In some reports breastfeeding has also improved vaccine responses. Several studies show that milk may actively stimulate the immune system of the offspring via transfer of anti-idiotypic antibodies and lymphocytes. This may explain why breastfeeding diminishes the risk of developing coeliac disease. Some investigations suggest that there may also be a similar effect on allergic diseases and autoimmune diseases, as well as inflammatory bowel diseases and certain tumours. This needs to be confirmed.

Bacterial Infections↗

PubMed1998

Effects of housing conditions and 5-HT2A activation on male rat sexual behavior.

Adult male rats were housed individually or in groups for a period of 39 days. In Experiment 1, the effects of housing conditions on sexual behavior and concurrent spontaneous "wet dog shaking" (WDS) were investigated. Individual housing significantly impaired male sexual behavior and resulted in a trend toward increased WDS. In Experiment 2, the effects of housing conditions were examined following administration of the serotonergic type 2A (5-HT2A) agonist DOI. Individual housing significantly increased DOI-induced WDS. The implications of these findings are discussed in the context of stress-induced corticosterone secretion and the possible regulatory effect on 5-HT2A receptors.

Amphetamines↗

PubMed1998

The antidepressant, nefazodone, attenuates corticosterone-induced increases in 5-HT2A receptor-mediated behaviors in the female rat.

The effects of chronic corticosterone administration on sexual behavior and on wet-dog shakes, a 5-HT2A mediated behavior, were investigated in the female rat. In addition, effects of the antidepressant nefazodone, a selective 5-HT2A receptor antagonist, both alone and in combination with corticosterone were examined. Testing was conducted in ovariectomized animals primed with estrogen and progesterone. Corticosterone was found to significantly increase sexual receptivity, sexual proceptivity and wet dog shakes. While nefazodone alone had no significant effects, it completely attenuated the corticosterone-induced increases in both sexual behavior and wet dog shakes. This suggests that corticosterone influences sexual behavior and wet dog shakes via a 5-HT2A receptor mechanism.

Animals↗

PubMed1998

Chronic stress effects on sexual behavior in male and female rats: mediation by 5-HT2A receptors.

The effects of chronic psychosocial stress on sexual behavior and on the serotonergic type 2A (5-HT2A) receptor-mediated behavior "wet dog shakes" (WDS) were investigated in male and female rats. In Experiment 1, both bilaterally adrenalectomized and sham-adrenalectomized female rats were assigned to either a psychosocial stress condition or a control condition for 62 days. On the 63rd day, estrogen-primed females were compared on measures of sexual behavior and WDS. Immediately after the behavioral tests, the same rats were primed with a subthreshold level of progesterone. Three hours after the administration of progesterone, rats were again scored for sexual behavior and WDS. Psychosocial stress was found to facilitate sexual behavior and increase WDS in sham-adrenalectomized female rats providing they were primed with both estrogen and progesterone. In Experiment 2, intact male rats were assigned to either the psychosocial stress condition or the control condition for 30 days. On the 31st day, males were compared on measures of sexual behavior and WDS. No significant differences were revealed on the spontaneous expression of sexual behavior and WDS. Subsequently, males were retested following the administration of the 5-HT2A agonist, DOI. Psychosocial stress resulted in a significant decrease in male sexual behavior and a concurrent increase in WDS, following the administration of DOI. Taken together, these results suggest that chronic psychosocial stress facilitates female sexual behavior and inhibits male sexual behavior, and that the effects of stress on sexual behavior may be mediated by 5-HT2A receptor activity.

Analysis of Variance↗

PubMed1998

Sexual behavior and wet dog shakes in the male rat: regulation by corticosterone.

The potential involvement of adrenal steroids in the regulation of 'wet dog shakes' (WDS) and sexual behavior was investigated in male rats treated or not with the serotonergic type 2A (5-HT2A) agonist DOI (5-HT2A receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane). In Experiment 1, the frequency of both spontaneous and DOI-induced WDS were compared in adrenalectomized and sham-adrenalectomized rats. Adrenalectomy significantly reduced the frequency of DOI-induced WDS. In Experiment 2, adrenalectomized and sham-adrenalectomized rats received either corticosterone or oil chronically and were again scored for WDS behavior. Corticosterone effectively blocked the adrenalectomy-induced reduction of WDS in the DOI treatment condition. In Experiment 3, intact male rats were chronically administered either corticosterone or oil treatment. Animals were then compared on measures of both spontaneous and DOI-induced WDS and sexual behavior. Corticosterone significantly increased WDS and inhibited sexual behavior in both the spontaneous and DOI treatment conditions. These results suggest that the adrenal steroid corticosterone is important in the regulation of WDS and sexual behavior in the male rat and that this regulation may be mediated by activity at 5-HT2A receptors.

Adrenalectomy↗

PubMed1998

Breastfeeding provides passive and likely long-lasting active immunity.

OBJECTIVES: The reader of this review will learn about the mechanisms through which breastfeeding protects against infections during and most likely after lactation, as well as possibly against certain immunologic diseases, including allergy. DATA SOURCES: I have followed the literature in the area closely for the last 30 to 40 years and have made repeated literature searches through MEDLINE, most recently in 1998. Textbooks and peer-reviewed journals have been sought for, as well as books representing meeting reports in English, French, German, and Spanish. RESULTS: Human milk protects against infections in the breastfed offspring mainly via the secretory IgA antibodies, but also most likely via several other factors like the bactericidal lactoferrin. It is striking that the defense factors of human milk function without causing inflammation, some components are even directly anti-inflammatory. Protection against infections has been well evidenced during lactation against, e.g., acute and prolonged diarrhea, respiratory tract infections, otitis media, urinary tract infection, neonatal septicemia, and necrotizing enterocolitis. There is also interesting evidence for an enhanced protection remaining for years after lactation against diarrhea, respiratory tract infections, otitis media, Haemophilus influenzae type b infections, and wheezing illness. In several instances the protection seems to improve with the duration of breastfeeding. Some, but not all studies have shown better vaccine responses among breastfed than non-breastfed infants. A few factors in milk like anti-antibodies (anti-idiotypic antibodies) and T and B lymphocytes have in some experimental models been able to transfer priming of the breastfed offspring. This together with transfer of numerous cytokines and growth factors via milk may add to an active stimulation of the infant's immune system. Consequently, the infant might respond better to both infections and vaccines. Such an enhanced function could also explain why breastfeeding may protect against immunologic diseases like coeliac disease and possibly allergy. Suggestions of protection against autoimmune diseases and tumors have also been published, but need confirmation. CONCLUSIONS: Breastfeeding may, in addition to the well-known passive protection against infections during lactation, have a unique capacity to stimulate the immune system of the offspring possibly with several long-term positive effects.

Breast Feeding↗

PubMed1998

P fimbriae and other adhesins enhance intestinal persistence of Escherichia coli in early infancy.

Resident and transient Escherichia coli strains were identified in the rectal flora of 22 Pakistani infants followed from birth to 6 months of age. All strains were tested for O-antigen expression, adhesin specificity (P fimbriae, other mannose-resistant adhesins or type 1 fimbriae) and adherence to the colonic cell line HT-29. Resident strains displayed higher mannose-resistant adherence to HT-29 cells, and expressed P fimbriae (P = 0.0036) as well as other mannose-resistant adhesins (P = 0.012) more often than transient strains. In strains acquired during the first month of life, P fimbriae were 12 times more frequent in resident than in transient strains (P = 0.0006). The O-antigen distribution did not differ between resident and transient strains, and none of the resident P-fimbriated strains belonged to previously recognized uropathogenic clones. The results suggest that adhesins mediating adherence to intestinal epithelial cells, especially P fimbriae, enhance the persistence of E. coli in the large intestine of infants.

Adhesins, Escherichia coli↗

PubMed1998

High turnover rate of Escherichia coli strains in the intestinal flora of infants in Pakistan.

The Escherichia coli flora of infants in developed countries is dominated by one or a few strains which persist for prolonged periods of time, but no longitudinal studies have been performed in developing countries. To this end, we studied the rectal enterobacterial flora in 22 home-delivered Pakistani infants during their first 6 months of life. Three colonies were isolated and species typed on each of 11 sampling occasions. E. coli isolates were strain typed using electromorphic typing of cytoplasmic enzymes, and their O serogroups were determined. There was a very rapid turnover of enterobacterial strains in the rectal flora of individual infants. On average, 8.5 different E. coli strains were found per infant, and several biotypes of other enterobacteria. Less than 50% of the infants were colonized with E. coli from their mothers, but strains of maternal origin were four times more likely to persists in the infants' flora than other E. coli strains. Enterobacteria other than E. coli were always of non-maternal origin, and Enterobacter cloacae and Klebsiella pneumoniae biotypes recovered from contaminated feeds were later identified in the infants' rectal flora. An early colonization with klebsiella or enterobacter was significantly associated with diarrhoea during the neonatal period, although these bacteria were not likely to be the cause of the disease. The results suggest that poor hygienic conditions result in an unstable and diverse enterobacterial flora, which may influence infant health.

Diarrhea↗