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Biomedical subjects

L A Hanson

Publications and source records attributed to L A Hanson.

At least 145 records · Page 8Linked to original sources
PubMed1993

An MTT-based method for the in vivo quantification of myotoxic activity of snake venoms and its neutralization by antibodies.

The reduction of the tetrazolium compound MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) was used as the basis for the development of a simple method for the quantitative estimation of metabolically active skeletal muscle tissue remaining after in vivo venom-induced myonecrosis. Using the venom of the snake Micrurus nigrocinctus as a potent myotoxic agent, this MTT-based technique was evaluated in comparison with available methods based on the measurement of creatine kinase (CK) activity, and a quantitative histological technique considered as a reference. Homogenates of the gastrocnemius muscle prepared in the presence of 1% Triton X-100 reduced MTT and this activity correlated closely with the number of viable cells in the tissue, as determined by histological evaluation. After venom injection, residual MTT-reducing activity of muscle homogenates showed higher correlation to the myonecrosis index obtained by histological analysis, than residual muscle CK activity. Using the new MTT-based assay, the ability of an anti-M. nigrocinctus equine antivenom to neutralize venom myotoxins was studied. The myotoxic activity of the venom was completely neutralized using 4 ml antivenom/mg venom, with a 50% effective dose (ED50) value of about 2.5 ml/mg. The MTT-based method described should be useful in the estimation and standardization of anti-myotoxic potency of antivenoms, and in the screening of other neutralizing agents, as a convenient and reliable alternative to the time-consuming quantitative histological methods.

Animals↗
PubMed1993

Altered dexamethasone responsiveness and loss of growth control in tumorigenic mouse lung cell lines.

Glucocorticoid hormones induce differentiation, inhibit proliferation, and, in mice, reduce carcinogen-induced tumorigenesis of lung epithelial cells. Therefore we examined dexamethasone effects on tumorigenic and non-tumorigenic mouse lung epithelial-derived cell lines. Non-tumorigenic cells were growth inhibited and exhibited CAT activity in pMMTV-CAT transfectants in response to dexamethasone. Tumorigenic cell lines exhibited a range of responses to dexamethasone. While one tumorigenic line was growth-inhibited and responsive in CAT assays, 2 other tumorigenic cell lines were unresponsive both in CAT and in growth assays. A fourth tumorigenic cell line exhibited intermediate sensitivity in CAT assays and was actually growth-enhanced by dexamethasone. Although no difference between cell lines was observed in the abundance of glucocorticoid receptor protein on Western blots, the least dexamethasone-responsive tumorigenic lines exhibited very little binding of 3H-dexamethasone. Clones of tumorigenic lines stably transfected with the rat glucocorticoid receptor gene were more dexamethasone-sensitive in CAT assays and were growth-inhibited by dexamethasone. These data suggest that the neoplastic progression of cell lines derived from mouse lung frequently involves the acquisition of diminished glucocorticoid responsiveness.

Animals↗
PubMed1993

Host response to Bothrops asper snake venom. Analysis of edema formation, inflammatory cells, and cytokine release in a mouse model.

As part of the characterization of the host reactivity to the venom of Bothrops asper, we investigated the inflammatory responses in the mouse footpad model. The subcutaneously injected venom induced a rapid increase of serum IL-6 concentration, which peaked between 3 and 6 h and returned to normal values at 12 h. In contrast, serum TNF-alpha and IL-1 alpha were not detectable at any time point studied. A myotoxic phospholipase A2 isoform purified from this venom, myotoxin II, was also able to induce a systemic IL-6 release when injected into the footpad. Both venom and myotoxin induced local edema and a leukocyte infiltrate accumulating in the muscle and subdermal tissue within 6 h. The infiltrate consisted predominantly of neutrophils at 6 and 24 h, but at later times, mononuclear cells also appeared. The edema, leukocyte infiltration, and IL-6 responses did not depend on the hemorrhagic activity of venom, since all three effects were seen after injection of (1) preneutralized venom, devoid of hemorrhagic activity, and (2) purified myotoxin II. Circulating platelet numbers were significantly decreased 30 min after venom injection and returned to normal after 12 h. The venom also induced a rapid inversion in the ratio of neutrophils to lymphocytes in peripheral blood, which did not normalize until 12 h later. The present observations suggest that venom, besides its cytotoxic properties, induces early hematologic and immunologic alterations. These findings may be of relevance in future treatment modalities.

Animals↗
PubMed1993

Biological and biochemical activities of Vipera berus (European viper) venom.

Vipera berus is widely distributed throughout the northern part of Europe and Asia. Characterization of several toxic effects of its venom in the mouse, as well as of in vitro enzymatic activities was performed. Vipera berus venom displayed in vitro proteolytic, fibrinolytic, anticoagulant, and phospholipase A2 activities. The i.p. LD50 of the venom for Swiss mice was 0.86 micrograms/g (95% confidence limits 0.71-1.01 microgram/g). Significant local tissue-damaging effects, including edema, hemorrhage and myonecrosis, were observed. The local edema was characterized by rapid onset, reaching a maximum after 0.5-1 hr, and with dose-dependent persistence. The hemorrhagic potency was measured by a skin test, giving a minimum hemorrhagic dose value of 3.2 micrograms. The venom also induced a moderate local myonecrosis, evidenced by histological evaluation of injected tissue (gastrocnemius), and by biochemical parameters (increase of plasma creatine kinase activity, and decrease of muscle residual MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide)-reducing activity). Characterization of the venom by SDS-polyacrylamide gel electrophoresis revealed 10 (reduced) or 11 (unreduced) main protein bands, which were further analyzed in relation to mol. wt and relative concentration by densitometry. A rabbit antiserum to V. berus venom recognized all main venom bands by immunoblotting. This antiserum cross-reacted to a variable extent with several crotaline venoms, as assessed by enzyme immunoassay.

Animals↗
PubMed1993

B-cell activation in duodenal mucosa after oral cholera vaccination in IgA deficient subjects with or without IgG subclass deficiency.

Alterations in duodenal Ig-producing cells induced by two oral cholera vaccinations were studied by two-colour immunofluorescence in mucosal tissue sections from adults with selective IgA deficiency (IgAD), either with (n = 7) or without (n = 9) frequent infections, infection-prone patients with combined IgAD and IgG subclass deficiency (IgGSD) (n = 7), and normal control subjects (n = 11). The proportion of IgG-producing cells prior to immunization tended to be lower in the symptomatic IgAD subjects than in the clinically healthy ones. In the first subgroup the absolute number of IgG cells per intestinal length unit was significantly increased after immunization (P < 0.04), and this tendency was also observed in the healthy IgAD subjects (6/9) and in those with combined deficiency (5/7). Very few IgAD subjects responded with an increase of IgM-producing cells. The normal controls responded variably in all major immunocyte classes, in the order IgA > IgG > IgM. Compared with these controls, the patients with combined IgAD and IgGSD showed significantly increased IgG1 (P < 0.01) and reduced IgG2 (P < 0.006) proportions, which was in accordance with their serum subclass levels. Our study showed that oral cholera vaccination preferentially activates intestinal IgG-producing cells in IgAD subjects. This result agreed with data recently obtained by ELISPOT in the same patients with regard to antibody-forming cells specific for cholera toxin. Both methods suggested that IgG rather than IgM antibodies are elicited as compensation for a lacking IgA response. However, our overall results showed that intestinal B-cell activation is quite variable after oral cholera vaccination. Although such vaccination might be of importance for enhancing mucosal immunity also in IgAD patients, a concurrent gut disease could possibly be aggravated by IgG-mediated mucosal immunopathology in the absence of anti-inflammatory IgA antibodies.

Adult↗
PubMed1993

IgA and IgG subclass deficiency in a poor population in a developing country.

The levels of IgG, IgG subclasses, IgM and IgA were determined in serum from 17 patients with IgA deficiency and severe or frequent infections, allergy and/or autoimmunity (median age 7 years, range 2-19), 11 healthy IgA-deficient adults and 35 controls (median age 7 years, range 2-19). In serum from all groups IgG, IgM and IgA antibodies were determined against beta-lactoglobulin, E. coli O antigens and poliovirus type 1 antigen. In saliva of 15 IgA-deficient patients and 12 of the controls IgG, IgM and secretory component-carrying antibodies against E. coli O antigens and poliovirus type 1 were determined. The majority of the studied individuals lived under poor socio-economic conditions in Brazil, with consequent heavy microbial exposure. One IgA-deficient patient with rheumatoid arthritis also had IgG2 deficiency but no infectious problems. Four out of the 35 controls without any obvious infectious problems were found with IgA or IgG subclass deficiency. One of the 11 healthy IgA-deficient adults was low in the IgG2 subclass, one in IgG1 and one in IgG3. Those with symptomatic IgA deficiency had significantly higher serum IgG than the controls, especially in the age group 6-11 years. This latter group also had significantly increased serum IgG1 and IgG2 levels when compared with the age-matched controls. Salivary IgM antibodies to E. coli and poliovirus antigens were significantly higher among the symptomatic IgA-deficient individuals than among the controls. It is not clear at present whether these increased Ig levels are secondary to frequent infections and/or part of mechanisms that may compensate for the IgA deficiency.

Adolescent↗
PubMed1993

Periodontal disease and dental caries in relation to primary IgG subclass and other humoral immunodeficiencies.

22 females and 3 males with primary hypogammaglobulinaemia (n = 6) or IgG subclass deficiencies with (n = 3) or without (n = 16) concomitant IgA deficiency were examined for periodontal disease and dental caries. Only 1 patient showed more tooth loss than that found in the normal Swedish population. 1 patient demonstrated advanced periodontal disease. No patient exhibited more severe dental caries than that of comparable normal Swedes. Microbiological samples from periodontal pockets and saliva showed recovery of potential periodontopathic and cariogenic bacteria within normal ranges. This study could not support the notion that immunodeficient subjects exhibit an increased risk of developing periodontal disease or dental caries.

Adult↗
PubMed1993

Early child health in Lahore, Pakistan: I. Study design.

In this paper, details are given of a community based follow up study of four areas: a village, a periurban slum, an urban slum and an upper middle class control group living in and around Lahore, Pakistan. The aim was to characterize the determinants of child health in a rapidly urbanizing community. The study was undertaken in two steps. An initial cross-sectional survey collecting socio-economic and demographic background information was carried out between March to August 1984. This was followed by a longitudinal study of 1476 infants representing the outcome of the pregnancies registered continuously between September 1984 to March 1987 among the 3242 families in the study. These infants were followed monthly from birth to 3 years of age and thereafter less frequently. In this communication we describe the study design, the study population, the organization and the research methodology used, including the reasons for drop outs from birth to 24 months of age. The internal consistency of the data is also presented. After the initial examination of the newborns within between 0-7 days of birth, the infants were visited monthly for 24 months making a total of 20911 examinations. At 24 months of age 70% of the infants were still in the study, 11% had died before reaching this age, 13% had moved from the area and 6% had refused to participate in the study. The economic, conditions, social structure, and the quality of life were found, not surprisingly, to vary significantly among the four areas. This community-based project provides new, critical and reliable information for local health planners. The study highlights the importance of the development of a useful model for research collaboration between institutions in developed and developing countries.

Child Welfare↗
PubMed1993

Early child health in Lahore, Pakistan: V. Feeding patterns.

The feeding practices of children (n = 1476) from birth to 24 months, as determined in a longitudinal study, in Lahore, Pakistan, are presented. Four socioeconomic groups at various levels of urbanization were included; a village, periurban slum, urban slum and an upper middle class. Initiation of breastfeeding was delayed in all the neonates. Sixty-five percent of the periurban slum mothers and 45% of the village mothers had not started breastfeeding at 48 hours after the birth of the infant. Prelacteal feedings, especially of herb water and honey, were the norm. Breastfeeding was highly prevalent. Eighty-seven to 98% of the infants in all the areas were breastfed at one month of age. Exclusive breastfeeding was rare, with 9% at one month, declining rapidly with age and being highly influenced by season. Partial breastfeeding was the most common mode of feeding. Water in addition to human milk was given by 45-73% of the mothers living in the urban slum, village and periurban slum at one month of age. Fresh animal milk and/or commercial formula was already being given at 1 month by 22-64% of the mothers in all areas. Commercial formula was the preferred food in the upper middle class, while in the other three areas it was rare and fresh animal milk was mainly used. More than 50% of the mothers in the village and in the periurban slum gave diluted animal milk even beyond the age of 10-15 months. In the upper middle class 50% of the infants were fed semisolids at the age of four months, while in the village, the periurban and the urban slum at 6 months of age only 10%, 12% and 47% of the infants received semisolids. The results of this study indicate that breastfeeding was highly prevalent in the three poorest areas. However, in all the areas initiation of breastfeeding was delayed and prelacteal feeding was the norm. Exclusive breastfeeding was rare, feeding bottles were used by 82-100% of the mothers to feed supplements and human milk substitutes, in the four areas.

Breast Feeding↗
PubMed1993

Early child health in Lahore, Pakistan: VI. Morbidity.

Morbidity patterns were studied according to the age, area of living, sex and season among 1476 monthly followed infants born during 1984-1987 in four socio-economically different areas in Lahore, Pakistan. Infections were responsible for 87.0% of the morbidity during the first two years of life. The overall monthly based morbidity was 77.0% between birth and 24 months of age; diarrhoeal diseases 30.3%, upper and lower acute respiratory tract infections (ARI) 22.4%, skin and eye infections 6.7% and skin rash 6.2%. The vaccine-preventable diseases were only 0.5% of the total. Anaemia and rickets were rare (2.0%), but commonly seen among the nutritional deficiencies. Diarrhoea, tetanus, septicaemia, ARI and infections of the skin and eyes were reported more during earlier ages and from the three poorer areas of living. Diarrhoeal diseases, respiratory tract, skin and eye infections, in particular, followed clear seasonal patterns, while scabies prevailed throughout the year. The presence of these many preventable infections and illnesses implies that proper planning of interventions must be forthcoming.

Age Factors↗
PubMed1993

Early child health in Lahore, Pakistan: IX. Perinatal events.

In Pakistan there are a number of acute problems related to maternal and infant health in the perinatal period. There is also lack of reliable data needed for the formulation of action strategies. To provide a database 1490 women have been followed from the 5th month of pregnancy in four different areas at various levels of urbanization and socio-economic development. After adjusting for gestational age, the proportion of newborns with weight for length < -2SDS in relation to the Swedish National Standard was 12-31% for boys and 12-25% for girls, the figure being highest in the most deprived area. Preterm birth was infrequent compared with IUGR. The overall prevalence rate of birth defects was 21% out of which 8% were severe defects. The overall perinatal mortality rate was 56/1000 births, with rates of 60, 75, 36 and 33/1000 births for the village, periurban slum, urban slum and the upper middle class. Two thirds of the deaths were related to either a continuation of intrauterine disturbances or severe congenital defects incompatible with life. One third of the deaths were due to infection; mostly diarrhoea, clinical sepsis and ARI. Neonatal mortality was significantly related to birth length (< -2SDS, odds ratio 5.5) and length of gestation (< 37 weeks, odds ratio 5.6) and was to a lesser extent related to weight (< -2SDS, odds ratio 2.0) and weight for length (< -2SDS, odds ratio 1.3). Forty percent of the mothers had weight for height below -2SDS, 23-35% had height < -2SDS. Forty percent of mothers from a subset within the cohort had a hemoglobin < 10 gm/dl and 20% showed signs of pre-eclampsia. This presentation raises the issue of expanding the current Child Survival Programs into the perinatal period as well.

Adolescent↗
PubMed1993

Impaired mucosal antibody response to cholera toxin in vitamin A-deficient rats immunized with oral cholera vaccine.

To investigate the importance of vitamin A in the ability to respond to oral antigen administration, rats were fed a vitamin A-free diet. The animals were immunized perorally three times with a mixture of cholera toxin (CT) and a commercial cholera vaccine. The total immunoglobulin A (IgA) concentration as well as the specific IgA anti-CT antibody levels in serum and bile was significantly lower in the vitamin A-deficient animals than in the paired fed controls (animals that were fed a normal commercial diet in an amount equal to the amount the deficient animals consumed), while the levels of total and specific anti-CT IgG were not affected to the same extent by the vitamin A deficiency. The number of IgA anti-CT antibody-producing cells in the mesenteric lymph nodes after immunization was also significantly lower in the vitamin A-deficient rats than in the control rats. Supplementation of the diet with retinyl palmitate restored the ability to mount an IgA antibody response to the antigen, since the level of specific IgA anti-CT antibodies in relation to the total IgA concentration was as high in the vitamin A-supplemented group as in the paired fed control group. Restricted diet intake by itself did not affect the ability to respond adequately to the antigen since there was no difference in IgA anti-CT antibody level between paired fed rats and those being fed ad libitum. Assessment of transforming growth factor beta in cell cultures revealed no difference between vitamin A-deficient and paired fed animals. In summary, vitamin A deficiency resulted in a decreased number of IgA-producing cells, decreased IgA production, and a reduced ability to respond with IgA antibodies to the oral cholera vaccine.

Administration, Oral↗
PubMed1993

Poliovirus antibody titres, relative affinity, and neutralising capacity in maternal milk.

Varying titres of secretory IgA antibodies to poliovirus type 1 were found previously in the milk of unvaccinated, lactating Pakistani mothers during two different years, reflecting the antigenic exposure on mucosal membranes. To study further the changes in the extent and the form of antigenic exposure reflected in the human milk, human milk samples from Pakistani, Indian, Japanese, and Swedish mothers were collected. The quality and the neutralising capacity of the antibodies was also studied. Secretory IgA, IgG, and IgM antibodies to poliovirus type 1 were determined using enzyme linked immunosorbent assay (ELISA) and relative affinity was measured in ELISA by elution with potassium thiocyanide. Microneutralisation tests were also performed. The higher secretory IgA antibody titres to poliovirus type 1 in the unvaccinated, naturally exposed Pakistani and Indian mothers' milk, compared with the Swedish and Japanese mothers, presumably reflect the epidemiological situation in these countries. Neutralising capacity and the relative antibody affinity seemed to be higher both in the Pakistani mothers and the group without natural exposure but only given inactivated poliovirus vaccine, that is the Swedish mothers, than the group meeting only live vaccine strains, that is the Japanese mothers.

Antibodies, Viral↗
PubMed1993

Anti-idiotypic antibodies to poliovirus antibodies in commercial immunoglobulin preparations, human serum, and milk.

Our previous studies have suggested that fetal antibody production can be induced by maternal antiidiotypic antibodies transferred to the fetus via the placenta. We tested commercial Ig, sera, and milk for the presence of anti-idiotypic antibodies to poliovirus type 1, using affinity chromatography combined with ELISA systems and virus neutralization techniques. Our results indicate that commercial Ig, serum, and milk samples contain antibodies recognizing idiotypic determinants on antibodies to poliovirus. Several lines of evidence support this conclusion. Thus, in an ELISA with poliovirus as a solid phase, binding of specific antibodies could be inhibited by addition of an eluate from the Ig preparation containing anti-idiotypic antibodies against poliovirus type 1. Also, antiidiotypic antibodies from pooled human Ig, serum, and colostrum samples against poliovirus bound directly to solid-phase-attached MAb against poliovirus type 1. In addition, in a competitive inhibition ELISA, where antiidiotypic antibodies isolated from the Ig preparation competed with the poliovirus antigen for binding to monoclonal or polyclonal idiotypic antibodies on the solid phase, inhibition of antigen binding was seen at low antigen concentrations. When single-donor serum or milk was used, this inhibition was even more pronounced and could be demonstrated at almost all antigen concentrations. The finding that anti-idiotypes are present in maternal serum and milk imply, in agreement with our previous studies, that anti-idiotypes may actively induce a specific immune response in the fetus without previous exposure to the antigen by being transferred across the placenta or by being passively transferred to the newborn via mother's milk.

Adult↗
PubMed1993

The effect of caloric supplementation on selected milk protective factors in undernourished Guatemalan mothers.

The level and avidity indices of specific antibodies against tetanus toxoid, Escherichia coli O6 and a pool of 10 common E. coli O antigens, as well as the concentration and daily output of lactoferrin and total secretory IgA (SIgA), were evaluated in the milk of moderately undernourished mothers who were in a random blind design divided into two groups and given different caloric supplementations. Group A received a high caloric supplement (500 kcal/d), and group B received a low caloric supplement (140 kcal/d). Determinations were done using ELISA in various modifications, except for lactoferrin, which was quantified by single radial immunodiffusion. The avidity indices were investigated as an evaluation of the antibody quality. In all the parameters evaluated, the only difference found between the two groups at the end of the supplementation period was in the content of total SIgA, which was lower in group B, both in concentration and daily output. However, the SIgA remained within the normal range. Increases as well as decreases in the levels of specific IgA antibodies occurred within both groups. Avidity was decreased in group B only against one of the antigens tested. We conclude that moderate undernutrition does not impair the levels of milk antibodies, and supplementation does not enhance them but prevents the decrease in the content of total milk SIgA. There is a suggestion that the avidity of certain antibody specificities could be hampered.

Antibodies, Bacterial↗