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Publications (633)
Background:
Diarrheal illnesses in young children cause morbidity and preventable deaths in developing countries. We evaluated two high doses of Salovum®[Antisecretory Factor] to treat diarrhea in young children and followed for recurrence 6 weeks post treatment.
Methods:
Forty children, 6-24 months old, admitted with acute diarrhea, to the Outp...
Whereas a neonate is born is sterile, immediate exposure to its mother's mucosal surfaces allows it to acquire microflora, which plays an important role in defense against potential pathogens. This initial stimulus helps the immature immune system of the newborn to develop the capacity to respond with specific immunologic tolerance while avoiding t...
We studied the response to high doses of egg yolk containing Antisecretory Factor (B221(®) , Salovum(®) ) in young children with acute diarrhoea, presenting to the Children's Hospital, Lahore, Pakistan.
In a randomised, placebo controlled trial, 36 children aged 7 to 60 months with acute diarrhoea of unknown aetiology, with mild to moderate dehydra...
Diarrhoea is a leading cause of childhood morbidity and mortality in both developed and developing countries. Worldwide, more than one million children under the age of five die each year as a result of this disease (1). Development of specific medical intervention in the form of vaccination against childhood diarrhoea is slow and has so far shown...
Objective. Genetic heterogeneity and risk factor distribution was analyzed in two previously proposed asthma phenotypes. Method. A sample of 412 subjects was investigated at 7-8, 12-13, and 21-22 years of age with questionnaires, skin prick tests, and genetic analysis of IL-4 receptor (IL4R) single-nucleotide polymorphisms. The sample was subdivide...
We reviewed the literature that is the basis for our proposal that (2→8)-α-Neu5Ac conjugates will be safe and effective vaccines for Group B meningococci (GBMs), Escherichia coli K1, and Pasteurella haemolytica A2. Although (2→8)-α-Neu5Ac is a virulence factor and a protective antigen of these three pathogens, it is also a component of normal tissu...
The transfer of host defence capacity to the human offspring provides a remarkable model of passive transfer of immunity. In fact it may also provide an example of active immunization.
The transfer of mucosal protection via breast feeding offers many additional advantages for the mother and infant. Through its contraceptive effects it increases the...
The Fc-α receptor (FcαR/CD89) is involved in IgA complex formation and may affect the development of IgA nephropathy (IgAN). In this study, we tested the genetic variations of the CD89 gene in relation to disease susceptibility in IgAN and the expression of soluble CD89 (sCD89) in sera of patients with IgAN and in controls. There was a significant...
There is a need for new microbicidal agents with therapeutic potential due to antibiotic resistance in bacteria and fungi. In this study, the structure-microbicidal activity relationship of amino acid residues 14 to 31 (sequence 14-31) from the N-terminal end, corresponding to the antibacterial alpha-helix of human lactoferrin (LF), was investigate...
Inheritance and genetic factors are supposed to influence susceptibility to asthma and allergy. We tested if single nucleotide polymorphisms (SNPs) in the IL4R gene were associated with susceptibility to such diseases, or if they were related to the phenotypic presentation of asthma and allergic rhinoconjunctivitis (ARC).
Three hundred and nine 12-...
Background: Intrauterine growth retardation (IUGR) is major risk factor for increased neonatal mortality and morbidity, with a considerable risk for permanent brain damage. The prevalence of IUGR in Pakistan 1 newborns has been reported as high as 15-24%. The mechanism behind this condition remains unclear. It has been shown that cytokines play an...
The aim of this study was to test our hypothesis that the urinary excretion of C-reactive protein (CRP), alpha 1-microglobulin (A1M), retinol-binding protein (RBP) and Clara cell protein (CC16) is increased in children with urinary tract infection (UTI) and relates to renal damage as measured by acute dimercaptosuccinic acid (DMSA) scintigraphy. Fi...
There is growing evidence of genetic risk for susceptibility to IgA nephropathy. Among several candidate genes related to immunological regulation in renal tissue, TGFB1 is known to be a contributor to proliferation and the development of fibrosis.
We analysed several SNPs in a region of this gene using 212 DNA samples from biopsy-proven IgA nephro...
Human milk contains numerous components, which have been linked to immune functions. Initially it was easy to recognise such
constituents as classical members of the immune system, for example antibodies and lymphocytes, but today the list is very
long. This is due to the fact that we have learnt for one thing that certain nutrients, for instance p...
After having been breast-fed for 17 months (as if my mother knew that I was deficient in IgA), I have kept in close contact
with maternal milk up into my present advanced age.
Unlabelled:
Immunological tolerance by the mother prevents rejection of the foetus, but aberrations may increase risk of abnormalities like spontaneous abortion, or foetal growth restriction. The neonate is normally colonized with mother's gut microflora, mainly composed of protective anaerobes. This least threatening form of microbial colonizatio...
Ingestion of Escherichia coli O83 bacteria by adults resulted in a transient irregular colonization leading to a serum antibody response in only four out of 14 cases examined. In all of three pregnant women, however, IgA antibodies against E. coli O83 antigen were released from colostral cells after similar bacterial ingestion although no serum ant...
Evidence suggests that risk of chronic diseases may be programmed during the foetal and early life of the infant. With high rates of low birthweight coupled with a rapid nutritional transition, low-income countries are facing an epidemic of chronic diseases. Follow-up of a cohort of adults born during 1964-1978 in an urban slum in Lahore, Pakistan,...
We are now entering 'the second golden era of vaccines'. The first gave us many good vaccines, but some inadequately protective and some with unacceptable side-effects. Worse, we have no adequate vaccines against some of the most killing diseases in the world, such as tuberculosis, malaria and HIV. The development within this second golden era will...
Today the WHO Growth Chart Standards, based on the growth of breastfed infants, are used. These growth curves solve the problem of the deviating observations for breastfed compared to non-breastfed infants using previous growth charts. Presently it is not clear how the mother's diet, especially the fat intake, influences the growth of the offspring...
We have previously shown that the generation of antibodies to a polysaccharide vaccine (Typhim Vi) is compromised in Pakistani adults born of a lower birth weight. To assess whether this represents a true B-cell-dependent deficit, we revaccinated subjects with a second dose of the same vaccine and with a polysaccharide-protein conjugate vaccine to...
Specimens of milk, serum and faeces were collected from 23 healthy women, as well as faeces from their newborn infants, at several occasions from one to nine weeks after delivery. The predominating faecal E. coli strains were typed with regard to five different K antigens. The most frequently occurring was K1, followed by K3 and K13. E. coli with t...
Clinical and virological findings in seven children diseased during early infancy are reported. Serological observations and virus isolations indicated a common etiology (Coxsackie B3 virus) although the clinical picture varied. In the neonatal period respiratory symptoms, most probably of central origin, dominated, whereas in older infants other c...
Using sensitive, and accurate immunodiffusion methods CRP could be demonstrated in 17 of 98 infants apparently healthy upon clinical examination. Thirteen of these sera only contained trace amounts of CRP (0.5-1 μg/ml). The only case which had quantifiable amounts of CRP and which did not become negative upon control turned out to have kidney abnor...
Evidence suggests that risk of chronic diseases may be programmed during the foetal and early life of the infant. With high rates of low birthweight coupled with a rapid nutritional transition, low-income countries are facing an epidemic of chronic diseases. Follow-up of a cohort of adults born. during 1964-1978 in an urban slum in Lahore, Pakistan...
Today the WHO Growth Chart Standards, based on the growth of breastfed infants, are used. These growth curves solve the problem of the deviating observations for breastfed compared to non-breastfed infants using previous growth charts. Presently it is not clear how the mother’s diet, especially the fat intake, influences the growth of the offspring...
The objective of this study was to investigate whether the appearance of virtual human models influences observers when judging a working posture. A task in which a manikin is manually assembling a car battery was used in the experiment. In total, 16 different pictures were presented to the subjects. All pictures had the same background, but includ...
We investigated whether egg yolk in the form of B221 (Salovum), a medical food containing antisecretory factor (AF) might be used for treatment of acute and prolonged diarrhoea.
240 children 6-24 months of age, half with acute diarrhoea (<7 days) and half with prolonged diarrhoea (> or = 7 days) were randomly given 2 g of B221 or placebo every 5 h...
The newborn receives, via the placenta, maternal IgG antibodies against the microbes present in its surroundings, but such antibodies have a pro-inflammatory action, initiating the complement system and phagocytes. Although the host defence mechanisms of the neonate that involve inflammatory reactivity are somewhat inefficient, this defence system...
To explore the relationship between calendar month of administration and antibody (Ab) response to vaccination in subjects from The Gambia and Pakistan, two countries with distinct patterns of seasonality.
Three cohorts were investigated: Responses to rabies and pneumococcal vaccine were assessed in 472 children (mean age 8 years, males 53%) from r...
We previously found the soluble interleukin 4 receptor (sIL4R) to be differently expressed in allergic asthma patients compared to healthy individuals. Here we present data demonstrating the involvement of the sequence variations, c.912-1003A > G, c.912-833T > C, c. 912-630A > G, and c.912-577A > G, in the expressional regulation of IL4R splice var...
The production of antibody by human colostral cells was assayed by the hemolysis-in-gel technique. When sheep erythrocytes coated with O antigens from frequently encountered Escherichia coli bacteria were used as detector cells and anti-IgA serum was added for development, numerous plaque-forming cells (PFC) were demonstrated in all samples tested....
The aim of the study was to determine the concentrations of serum antibodies against Haemophilus influenzae type b in preschool children in relation to the distribution of idiotypic antibodies 1 and 2 (Id-1 and Id-2) and the exposure to breastfeeding in infancy. Sera were obtained from 74 control children recruited in an earlier case-control study...
Microbial exposure and the immune system of the newborn The newborn starts to be colonized in the upper respiratory tract and gastrointestinal tract, as well on the skin, directly from birth onwards. Delivery next to the anus exposes the newborn to the mother's intestinal microflora, in which harmless anaerobes are predominant, but where aerobic an...
Although intrauterine growth retardation (IUGR) is a major risk factor for increased neonatal mortality and morbidity, the mechanisms behind it are not clear. We analyzed cytokine gene expression and gene polymorphisms in infants with and without IUGR in Pakistan, where IUGR is very common. 45 IUGR and 55 control mother/infant pairs were studied. m...
Karger is a medical publisher, scientific publisher and biomedical publisher of print and online journals and books.
Few studies have presented three-dimensional car-driving postural information. This laboratory study investigated drivers' preferred postures, preferred interior dimensions and how they characterise their postures. The minimum-maximum intervals of preferred angles corresponded well with other experimental studies and were larger than intervals for...
Human milk contains numerous components like antibodies, cytokines, hormones, enzymes, and major proteins like lactoferrin and α-lactalbumin with multiple activities (microbicidal, tumoricidal, anti-inflammatory). Waiting for its own immune system to take over its host defense, the infant needs help from the mother. In higher animals such as humans...
This chapter illustrates the immunodeficiencies resulting from various forms of undernutrition and the possible clinical consequences. Malnutrition may lead to impairment of many aspects of host defense. It is a complex state ranging from undernutrition with deficiencies of all nutrients (as in hunger disease) to a deficiency limited to a single mi...
Allergic diseases are defined as hypersensitivity reactions caused by the immune system reacting erroneously to external material to which it normally should not react. There are two types of allergic disease. Most common and complex, both clinically and pathogenetically, are the atopic allergies such as asthma, hay fever and anaphylaxis caused by...
Severe forms of periodontitis are suggested to have a genetic basis.
The aim of the present investigation was to study the association of gene polymorphisms related to some immune regulation components (G-308A TNFA, Q551R IL-4RA and C-159T CD14) with severe chronic periodontitis.
Sixty patients (aged 36-74 years; mean 54.5+/-8.5) with severe and ge...
Epidemiological studies in humans have shown that perinatal nutrition affects health later in life. We have previously shown that the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) in the maternal diet affects serum leptin levels and growth of the suckling pups. The aim of the present study was to investigate the long-term effects of variou...
Fetal and postnatal nutrition have long-term effects on the risk for development of diseases late in life in humans and animals. The aim of the present study was to investigate the effect of dietary deficiency of essential fatty acids (EFA) in the perinatal period on later body weight and bone mass. During late gestation and throughout lactation, r...
PUFA and their metabolites are important regulators of bone formation and resorption. The effect of PUFA on bone growth may be especially striking during the perinatal period. The aim of the present study was to investigate the effect of diets with different n-6:n-3 fatty acid (FA) ratios during the perinatal period on bone parameters in the adult...
Development of asthma is likely to depend on a complex interaction between environmental and genetic factors. Several groups have suggested the gene of the IL-4 receptor alpha chain (IL4R) as a candidate gene for the development of asthma, although association with single polymorphisms has shown contradicting results.
We chose to analyse IL4R gene...
The aim of the study was to try to induce anti-secretory factor (AF) in human milk and possibly prevent mastitis.
Forty mothers who had normal deliveries and healthy full-term infants were randomly divided into two groups, 3-7 days postpartum. The experimental group received a food inducing AF. The control group received the same type of food, with...
Searching for a possible explanation for the phenotypic heterogeneity in IgG3 deficiency, we studied the antibody response to a polysaccharide and a protein antigen in IgG3-deficient (IgG3d) adults after vaccination with Haemophilus influenzae type b capsular polysaccharide (Hib CP) conjugated to tetanus toxoid. Distribution of isotypes, idiotypes,...
In search for a possible explanation of the phenotypic heterogeneity in selective immunoglobulin (Ig)A deficiency, we studied the IgG2 antibody response to meningococcal polysaccharide A (PSA) in IgA-deficient (IgAd) individuals after vaccination with meningococcal A + C polysaccharide vaccine. Two groups of IgAd individuals, one frequently infecte...
Prevalence of allergy is increasing in many countries and might be related to changed environmental factors, such as dietary fatty acids (FA). The present study investigates whether dietary ratio of n-6 to n-3 FA influences the induction of immunological tolerance to ovalbumin (OA) in neonatal rats. During late gestation and throughout lactation Sp...
Substantial evidence exists linking small size at birth to later-life susceptibility to chronic disease. Evidence is also emerging that some components of immune function may be programmed in early life. However, this evidence is limited and requires confirmation.
We investigated the association between size at birth and response to vaccination in...
The TNF2 allele at position -308 of the tumor necrosis factor (TNF)-alpha gene is associated with high TNF production. The purpose was to study the association of this gene polymorphism with rejection episodes and graft survival after kidney transplantation.
A retrospective analysis of transplant outcomes of patients who only had been treated with...
The aim was to study the impact of simple healthcare interventions in 0-24-month-old children living in rural communities outside Lahore, Pakistan. Newborns belonging to four birth cohorts were followed monthly from 0-24 months of age living in rural communities. Three cohorts were from the same village: Cohort A (1984-1987), n = 485; Cohort B (199...
The present study examines whether dietary essential fatty acid (EFA) intake influences the induction of oral tolerance to ovalbumin (OA) in neonatal and adult rats. During late gestation and throughout lactation Sprague-Dawley rats were fed a diet supplemented (S) with EFA (7% soybean oil), or a diet deficient (D) in EFA (7% hydrogenated lard). Th...
Rheumatoid arthritis (RA) is a genetically complex disease with many possible phenotypes. We investigated IL10 and TNFA gene polymorphisms in a group of Swedish women and men with RA compared with healthy individuals to estimate combinations of alleles specific for the disease.
We analyzed 264 patients with RA and 286 healthy controls for biallelic...
The aim of our study was to estimate the prevalence and severity of allergic rhinitis, rhinoconjunctivitis, and eczema in Costa Rican schoolchildren. We have reported asthma prevalence in the same cohort elsewhere. A questionnaire based survey was conducted on a random sample of children (n = 6144), aged 6-7 years and 13-14 years from 75 educationa...
Protective factors in human milk act on mucosal membranes in the upper and lower respiratory tract and in the gastrointestinal tract. The way in which breastfeeding may reduce the risk of infections in a more remote site such as the urinary tract will be elucidated.
Conclusion: The protective effect of breastfeeding on the urinary tract illustrates...
In most individuals minute amounts of food proteins pass undegraded across the intestinal mucosa and trigger antibody formation. Children with coeliac disease have enhanced antibody production against gliadin as well as other dietary antigens, e.g. beta-lactoglobulin, in cow's milk. Antibody avidity, i.e. the binding strength between antibody and a...
Strategies to prevent children from developing allergy have been elaborated on the basis of state-of-the-art reviews of the scientific literature regarding pets and allergies, building dampness and health, and building ventilation and health. A similar multidisciplinary review of infant feeding mode in relation to allergy has not been published pre...
Coeliac disease (CD) is known to have a strong genetic background. We analyzed the association between serological markers of CD and the -1087 IL10 and -308 TNFA gene polymorphisms in Swedish patients. A higher frequency of the TNF2 allele was present in the patients compared with the controls (p < 0.0001). The frequency of the AA genotype of the I...
The mucosal surface of the gastro-intestinal tract is our major interface to the environment. Much of the control of the immune response to the myriads of antigen present at this interface is mediated by professional antigen-presenting dendritic cells (DCs). They monitor fully the true nature of the antigenic challenge and provide this information...
Breast-feeding provides many advantages to the offspring, but presently there is an ongoing debate whether or not it prevents allergy any better than certain formulas. This report reviews the mechanisms involved and discusses how breast-feeding may protect against allergy.
The review builds on an internet-based literature search in addition to our...
A disturbance of the integrity of the intestinal epithelium with an increased risk for bacterial translocation is one of the suggested factors underlying the increased incidence of infections and septicaemia during vitamin A deficiency. In the present study the effects of vitamin A deficiency on the enzymic activity of enterocytes in response to ba...
The newborn's immune system grows fast from a small size at birth by exposure primarily to the intestinal microflora normally obtained from the mother at and after birth. While building up its immune system, the infant is supported by the transplacental IgG antibodies, which also contain anti-idiotypic antibodies, possibly also actively priming the...
Severe forms of periodontitis are suggested to have a genetic basis.
The aim of the present investigation was to study association of an IL10 gene polymorphism (G to A transition at the -1087 position) with severe chronic periodontitis.
Two groups of Swedish Caucasian subjects were included. One group consisted of 60 patients (aged 36-74 years; mea...
In this study, we investigated the anti‐inflammatory effects of orally administered human lactoferrin (hLF) and two peptides, based on the bactericidal region of hLF (HLD1 and HLD2), on the course of experimental colitis. Acute colitis was induced in C57Bl/6 mice by giving 5% dextran sulphate (DX) in the drinking water. The mice were killed after 2...
Lactoferrin, a glycoprotein present in milk, mucosal secretions and neutrophils contributes to host defense. We have previously shown that orally given milk lactoferrin (LF) mediates anti-infectious and anti-inflammatory activities in vivo. Moreover, we have shown that LF could inhibit the LPS-induced IL-6 secretion in a human monocytic cell line,...
Child mortality in diarrhoeal disease is increased significantly by vitamin A deficiency in poor countries. The pathological mechanisms are not known in detail. However, in this paper we report that vitamin A-deficient Wistar rats had much reduced IgA+ plasma cells in the ileal lamina propria (eightfold reduction from 470 cells/mm(2), P = 0.009), a...
The supply of polyunsaturated fatty acids (PUFA) is important for optimal fetal and postnatal development. We have previously shown that leptin levels in suckling rats are reduced by maternal PUFA deficiency. In the present study, we evaluated the effect of maternal dietary intake of (n-3) and (n-6) PUFA on the leptin content in rat milk and serum...
The aim of our study was to determine the prevalence of asthma and related respiratory symptoms in school children from Costa Rica during the last 10 years, from 1989 to 1998. Using nationally representative samples of school children from Costa Rica during the last 10 years we have performed three studies. Altogether 9931 children were investigate...
Sets of sera were obtained from 30 children <6 years of age with invasive type b (Hib) infection and their mothers. Duration and mode of breast-feeding were monitored. Titers of IgG1, IgG2, IgA and IgM antibodies against Hib capsular polysaccharide were determined in sera taken during the acute illness and during early and late convalescence.
Child...
The immune system of the human newborn is of very limited size. It expands rapidly, especially due to the exposure to the gut microflora. Normally the newborn is colonized with microbes from the mother's intestinal flora at and after delivery. The many defence factors of the mother's milk include large amounts of secretory IgA antibodies produced b...
The newborn has an immune system, very limited in size at birth and its postnatal expansion and maturation takes time. In the meantime the transplacental IgG antibodies from the mother play an important role for the protection of the infant. However, these antibodies act in tissues and induce inflammation and are energy-consuming. In contrast, the...
We have previously shown that maternal intake of essential fatty acids during late gestation and lactation affects the level of serum leptin in pups. The aim of the present study was to investigate the effect of dietary essential fatty acids on leptin content in the milk of rat dams and leptin expression in white adipose tissue of pups during the s...
The immune system of the human newborn is of very limited size. It expands rapidly, especially due to the exposure to the gut microflora. Normally the newborn is colonized with microbes from the mother's intestinal flora at and after delivery. The many defence factors of the mother's milk include large amounts of secretory IgA antibodies produced b...
We have previously demonstrated that rats fed ovalbumin (OVA) develop a tolerogenic activity in serum, which upon transfer induces tolerance to OVA and suppression of the immune response to a bystander antigen. Here, we have extended these studies and analysed if the tolerogenic activity in serum could suppress an established immune response in the...
The association between allergy markers and asthma and allergic rhinitis is stronger in countries with a Western lifestyle than in rural areas of Africa and Asia. We examined the relationship among allergy markers, asthma, rhinitis, and eczema in a case-control study of 198 schoolchildren, 10-13 years of age, living in Costa Rica, a Latin American...