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L Hammarström

Publications and source records attributed to L Hammarström.

At least 55 records · Page 3Linked to original sources
PubMed2000

Mapping of the chicken immunoglobulin heavy-chain constant region gene locus reveals an inverted alpha gene upstream of a condensed upsilon gene.

Chicken antibodies are increasingly being used as diagnostic and therapeutic tools. As only the genomic organization of the micro encoding gene was previously known, we analysed the chicken immunoglobulin Y (IgY) and IgA (upsilon and alpha chain) immunoglobulin heavy-chain constant region (IGHC) genes and the organization of the chicken IGHC locus. The alpha gene is encoded by four separate exons, whereas, surprisingly, there is no intervening DNA sequence between the CH1 and CH2 domains of the IgY heavy chain, which is thus encoded by three exons separated by two introns. DNA sequence analysis shows that the exon boundaries of the chicken IGHC genes are not consistent with published domain borders. Furthermore, differences in DNA sequence confirm the existence of IgY, IgA and IgM allotypes in chickens. Finally, our results show that the IGHC genes of chicken (IgY, IgA and IgM) are all colocated on chromosome E18C15W15, where the alpha gene is located upstream of the upsilon gene in an inverted transcriptional orientation. The distances between the mu and alpha genes and the alpha and upsilon genes are about 18 and 15 kilobases, respectively, and thus, the size of the whole chicken IGHC locus is approximately 67 kilobases.

Animals↗
PubMed2000

Expression of amelin and amelogenin in epithelial root sheath remnants of fully formed rat molars.

OBJECTIVE: To study the expression patterns of 2 enamel proteins, amelin and amelogenin, in the epithelial cells of the root sheath of fully formed rat molars. STUDY DESIGN: Twelve Sprague-Dawley rats, 50, 65, and 85 days of age, were used in this study. The maxillae of the rats were dissected free, and sagittal serial sections were made through the mesial root of the first molar. In situ hybridization of amelin and amelogenin mRNAs was performed, and immunohistochemical examinations of the corresponding proteins in the epithelial cells of the root sheaths of fully formed rat molars were performed. Antibodies against epidermal keratins were used to identify epithelial root sheath remnants. RESULTS: A group of epithelial cells, enclosed at the border between cellular cementum and dentin, expressed and synthesized amelin, but not amelogenin. Another group of epithelial cells, forming islands or strands, which were partially or totally incorporated in the matrix of the cellular cementum, expressed and synthesized both amelogenin and amelin. A third group of epithelial cells at the periphery of the cellular cementum expressed neither of the 2 proteins. Epithelial cells at the surface of acellular cementum did not express either of the 2 proteins. CONCLUSION: This study showed that the epithelial root sheath remnants in rat molars express and synthesize amelogenin, as well as amelin. However, there are marked regional differences. The roles of the enamel proteins in the formation of the radicular hard tissues of the rat molars and in the maintenance of the periodontal tissues remain to be clarified.

Amelogenin↗
PubMed2000

Treatment of enterotoxigenic and enteropathogenic Escherichia coli-induced diarrhoea in children with bovine immunoglobulin milk concentrate from hyperimmunized cows: a double-blind, placebo-controlled, clinical trial.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) and enteropathogenic Escherichia coli (EPEC) are important causes of diarrhoea in young children and are associated with significant mortality rates. Passive immunization with antibodies from immunized cows has previously been shown to be effective as prophylaxis against E. coli-induced diarrhoea and therapeutically against rotavirus and cryptosporidia-induced diarrhoea. METHODS: We tested the therapeutic efficacy of an oral bovine immunoglobulin milk concentrate (BIC) from cows hyperimmunized with ETEC and EPEC strains, in a randomized, placebo-controlled study in children with E. coli-induced diarrhoea. Eighty-six children between 4-24 months of age attending the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B) with E. coli-induced diarrhoea (63 EPEC/ETEC and 23 with other diarrhoeagenic E. coli) were randomly assigned to receive orally administered BIC (20 g) containing anti-ETEC/EPEC antibodies or a placebo preparation daily for 4 consecutive days. Daily stool output, intake of oral rehydration solution (ORS), stool frequency, and presence of diarrhoeagenic E. coli strains in the stool were monitored for 4 days. RESULTS: Children in the treatment group tolerated the BIC with no side effects. There were no significant differences between the two groups with regard to ORS intake, stool output, frequency of diarrhoea, or clearance of pathogen. Nor was there any significant alteration in the duration of diarrhoea. CONCLUSIONS: In contrast to the prophylactic efficacy of anti-E. coli BIC and the therapeutic efficacy of a similarly prepared anti-rotavirus BIC, antibodies from hyperimmunized cows appear to have no significant therapeutic benefit in the treatment of acute diarrhoea due to EPEC/ETEC.

Acute Disease↗
PubMed1999

A putative susceptibility locus on chromosome 18 is not a major contributor to human selective IgA deficiency: evidence from meiotic mapping of 83 multiple-case families.

Previous reports of an association between constitutional chromosome 18 abnormalities and low levels of IgA suggested that this chromosome contains a susceptibility locus for selective IgA deficiency (IgAD), the most frequent Ig deficiency in humans. IgAD is genetically related to common variable immunodeficiency (CVID), characterized by a lack of additional isotypes. Our previous linkage analysis of 83 multiple-case IgAD/CVID families containing 449 informative pedigree members showed a significantly increased allele sharing in the chromosome region 6p21 consistent with allelic associations in family-based and case-control studies and provided the evidence for a predisposing locus, termed IGAD1, in the proximal part of the MHC. We have typed the same family material at 17 chromosome 18 marker loci with the average intermarker distance of 7 cM. A total of 7633 genotypes were analyzed in a nonparametric linkage analysis, but none of the marker loci exhibited a significantly increased allele sharing in affected family members. In addition, reverse painting and deletion mapping of a panel of constitutional chromosome 18 deletions/translocations showed the presence of IgA-deficient and IgA-proficient patients with the same abnormality and did not reveal a region commonly deleted. The linkage analysis of chromosome 8 and 21 regions involved in reciprocal translocations t(8;18) and t(18;21), which were identified in two patients lacking IgA, did not disclose a significant allele sharing. Although these results do not exclude the presence of a minor predisposing locus on this chromosome, such a putative locus would confer a population risk of developing IgAD/CVID much lower than IGAD1.

Case-Control Studies↗
PubMed1999

Targeting of human switch recombination breakpoints: implications for the mechanism of mu-gamma isotype switching.

We recently characterized the allelic variants of the human Sgamma4 region which makes it possible to accurately identity and map Smu-Sgamma4 fragments from in vivo switched B cells. Twenty-six fragments were identified and a comparison was made with all previously published Smu-Sgamma sequences ( n = 82). Switch recombination outside the region flanking the Sgamma repeat sequence is a rare event in vivo and differences previously observed in patterns between in vitro and in vivo switched B cells appear to be artefactual and due to constraints of the methods used. Furthermore, internal deletions in the switch regions are common, but do not appear to be involved in isotype stabilization. A slight preference for switching to the B (SNIP) site was observed, suggesting a limited importance of both the B and A (SNAP) in the switching process. Mutations can be identified on either one or both sides of the switch junction, showing involvement of an error-prone process, and the pattern of mutations/substitutions at and around the junctions shows non-random nucleotide replacements by the enzyme(s) involved which may help in its future identification.

Alleles↗
PubMed1999

Fungal prophylaxis by reduction of fungal colonization by oral administration of bovine anti-Candida antibodies in bone marrow transplant recipients.

Candida overgrowth and invasion constitute a serious threat with a high mortality in BMT recipients. Currently available topical antifungal prophylaxis is largely ineffective, and as resistance to existing, absorbable drugs for systemic use is rapidly developing, new forms of therapy are needed. We investigated the effect of oral treatment of BMT recipients with a bovine immunoglobulin product derived from animals immunized against several Candida species. The natural Candida colonization was first followed in 19 patients to establish the colonization pattern. Half of the patients were found to be colonized prior to transplantation and altogether 72% were colonized at some point during follow-up. Those with a high pre-transplant concentration of Candida in saliva (>100 CFU/ml) remained colonized throughout the BMT treatment period. The therapeutic effect was monitored in two other patient groups. The first group consisted of nine patients, where, due to a low number of primary colonized patients, response in colonized patients was suggestive of a therapeutic effect. In the second group, 10 patients with a high level of colonization (>100 CFU/ml) were given 10 g daily of the product in three divided doses. The results suggest a treatment-related reduction in Candida colonization in a majority (7/10) of patients and one patient became completely negative. As no adverse effects were noted, our findings encourage additional studies in immunocompromised, transplant patients.

Administration, Oral↗
PubMed1999

Response of dental follicular cells to the exposure of denuded enamel matrix in rat molars.

Recent studies have indicated that cementum formation can be induced when dental follicular cells are exposed to enamel matrix. The purpose of the present investigation was to study this cementum formation and the appearance of the cells involved, including their expression of collagen types alpha1(I), alpha1(II) and alpha1(III) mRNAs, during this process by means of light microscopy and in situ hybridisation. The mandibular first molars of 5-d-old rats were surgically taken out, their enamel epithelium was removed, and then the crowns were re-inserted with the occlusal surface downwards in their crypts to allow the follicular cells to come in contact with the denuded enamel matrix. After observation periods of 2-14 d, the teeth were prepared for light microscopic examination and in situ hybridisation. A monolayer of follicular cells in contact with the exposed enamel matrix changed their morphology and increased their expression of collagen type I mRNA as early as 2-4 d after exposure to the enamel matrix. A cementum-like tissue was formed at the surface of the enamel matrix. Collagen type II mRNA was never expressed in the tissues studied, whereas collagen type III mRNA was weakly expressed in the follicular cells throughout the experiment.

Amelogenesis↗
PubMed1999

Genetic linkage of IgA deficiency to the major histocompatibility complex: evidence for allele segregation distortion, parent-of-origin penetrance differences, and the role of anti-IgA antibodies in disease predisposition.

Immunoglobulin A (IgA) deficiency (IgAD) is characterized by a defect of terminal lymphocyte differentiation, leading to a lack of IgA in serum and mucosal secretions. Familial clustering, variable population prevalence in different ethnic groups, and a predominant inheritance pattern suggest a strong genetic predisposition to IgAD. The genetic susceptibility to IgAD is shared with a less prevalent, but more profound, defect called "common variable immunodeficiency" (CVID). Here we show an increased allele sharing at 6p21 in affected members of 83 multiplex IgAD/CVID pedigrees and demonstrate, using transmission/diseqilibrium tests, family-based associations indicating the presence of a predisposing locus, designated "IGAD1," in the proximal part of the major histocompatibility complex (MHC). The recurrence risk of IgAD was found to depend on the sex of parents transmitting the defect: affected mothers were more likely to produce offspring with IgAD than were affected fathers. Carrier mothers but not carrier fathers transmitted IGAD1 alleles more frequently to the affected offspring than would be expected under random segregation. The differential parent-of-origin penetrance is proposed to reflect a maternal effect mediated by the production of anti-IgA antibodies tentatively linked to IGAD1. This is supported by higher frequency of anti-IgA-positive females transmitting the disorder to children, in comparison with female IgAD nontransmitters, and by linkage data in the former group. Such pathogenic mechanisms may be shared by other MHC-linked complex traits associated with the production of specific autoantibodies, parental effects, and a particular MHC haplotype.

Alleles↗
PubMed1999

Passive immunity against rotavirus in infants.

Passive immunity against a variety of gastrointestinal infections, using orally administered human antibodies, has been tried in a number of clinical trials. Recently, antibodies from other species such as cows and chickens, which have shown efficacy in experimental animal systems, have also been tried in humans. This review summarizes published data on the use of immunoglobulin-containing preparations for prophylaxis and therapy against rotavirus infections in infants and children, and directions for their future use are suggested.

Administration, Oral↗
PubMed1999

Expression of collagen alpha1(I) mRNA variants during tooth and bone formation in the rat.

Collagen alpha1(I) mRNA is composed of two variants of 5 and 6 kb, differing in the length of the 3' untranslated region. In this work, the nucleotide sequences of the two rat mRNA variants were compared, and their expression pattern in cells forming bone, dentin, and cementum were analyzed. The sequences were determined from cDNA inserts of tooth and bone libraries plus directly from PCR fragments, obtained from bone. A total of 5721 bases of the rat collagen alpha1(I) sequence from cDNA of tooth and bone was determined. All sequences of the short variant were represented in the long variant. Only the alternatively poly-A additions gave rise to the variants in hard tissue. Two oligonucleotides were chosen as probes, one of which recognized, on Northern blots, the two bands of 5 and 6 kb, and the other the 6-kb variant only. The oligonucleotides were used in in situ hybridization experiments, for study of the distribution of the variants in different extracellular matrix-forming cells. Osteoblasts, odontoblasts, and cementum-associated cells were closely examined in sections from rat maxillae from 2 to 25 days of age. A similar or identical pattern of mRNA expression was observed with both oligonucleotides, indicating that the two mRNA variants were co-expressed in all cases.

3' Untranslated Regions↗
PubMed1999

Activation of human B-lymphocytes by Prevotella intermedia.

Black pigmented Gram negative Prevotella intermedia is a potential pathogenic bacterium in periodontal disease. Lipopolysaccharides (LPS) from Gram negative bacteria are the main antigens that stimulate antibody production and cytokine synthesis. Many reports indicate a strong correlation of specific antibodies of the immunoglobulin G (IgG) class with antigens of periopathogenic bacteria in periodontal disease. The aim of this study was to measure lymphocyte proliferation and immunoglobulin (IgA, IgG and IgM) production from B-lymphocytes in response to P. intermedia stimulation. P. intermedia was originally isolated from human periodontal pockets by means of a gingival crevice lavage method. The periodontal pocket was washed with salt solution and the solution was then aspirated into a cannula for further culturing in the laboratory. The identification of P. intermedia was made on Brucella agar. Lymphocytes were isolated from human peripheral blood. P. intermedia was added to the lymphocytes in concentrations from 0.005% to 0.1%. The immunoglobulin production was measured by enzyme-linked immunosorbent assay (ELISA). The results showed that IgA and IgG were produced in response to stimulation with P. intermedia. The IgG response was dose-dependent. No stimulation of IgM production was obtained. It is concluded from the present observations that P. intermedia can stimulate proliferation of lymphocytes and production of IgA and IgG.

Antibodies, Bacterial↗
PubMed1998

Characterization of human gamma 4 switch region polymorphisms suggests a meiotic recombinational hot spot within the Ig locus: influence of S region length on IgG4 production.

Human gamma4 gene RFLPs, revealed after BamHI digestion, show IGHG4 alleles of 9.0 (9.2), 9.4, and 9.6 kb at various frequencies in different ethnic populations. Studies in immunodeficient individuals have previously suggested that the 9.4 BamHI allele is associated with a higher serum level of IgG4 than the 9.0 (9.2) BamHI allele, but it is not clear whether this is associated with the S region itself or other control elements. In addition, a duplication of the 9.4-kb gamma4 allele has recently been observed in a high proportion of normal donors. We therefore undertook a study of the structural basis for the difference in Ab levels in the various gamma4 alleles. We demonstrate that the Sgamma4 alleles differ in length due to deletions and insertions of a varying number of 79-bp Sgamma4 repeat units. Two novel RFLPs, 8.8 and 9.1 kb, were also observed. The alleles are likely to be generated by unequal crossing over, and the breakpoints cluster in Sgamma4 repeat units that contain chi-like motifs, implicating chi-like sequences in the meiotic recombination. Our data support the idea that the 9.4-kb BamHI allele is more productive than the 9.0 (9.2)-kb allele in normal healthy donors, possibly due to the extended switch regions, whereas duplication of the gamma4 gene has no effect on switching and IgG4 serum levels.

Base Sequence↗
PubMed1998

Ataxia-telangiectasia and T-cell leukemias: no evidence for somatic ATM mutation in sporadic T-ALL or for hypermethylation of the ATM-NPAT/E14 bidirectional promoter in T-PLL.

The ATM gene deficient in ataxia-telangiectasia, a recessive multisystem disease associated with a high risk of lymphomas and leukemias, was found previously to be inactivated in a rare sporadic malignancy, T-cell prolymphocytic leukemia (T-PLL), which is often associated with cytogenetic aberrations of chromosome 14. The ATM gene was shown to sustain frequent loss-of-function mutations in T-PLL tumor cells, consistent with functioning as a tumor suppressor gene in this leukemia. To investigate the possibility of nonmutational or nonrecombinational mechanisms of T-PLL development, we have used bisulfite genomic sequencing to analyze DNA methylation in the putative bidirectional promoter region of the closely linked ATM and NPAT/E14 genes within the CpG island at 11q22-q23. We show that this region is completely demethylated in lymphocytes expressing ATM; however, no extensive hypermethylation was found in 9 T-PLL tumor DNA samples without evidence of ATM/p53 mutations. Because acute T-cell lymphoblastic leukemias (T-ALL) were also observed in ataxia-telangiectasia patients and T-ALL tumor cells contain chromosome 14 abnormalities, 19 presentation samples of T-ALL patients were analyzed for ATM mutations. Although T-ALL patients exhibited rare nucleotide substitutions not previously found in ATM, all were identified in the germ-line, indicating constitutional polymorphisms, potentially confined to ethnic subpopulations. The absence of somatic nucleotide changes in ATM in T-ALL as compared with T-PLL suggests a distinct pattern of genetic events in the development of the two leukemias.

Ataxia Telangiectasia↗
PubMed1998

Treatment of Helicobacter pylori infection in infants in rural Bangladesh with oral immunoglobulins from hyperimmune bovine colostrum.

BACKGROUND: Antibodies from hyperimmune bovine colostrum have been shown to be effective in treatment against a variety of microorganisms, including Helicobacter pylori in adults. AIM: To test this form of treatment in a small group of H. pylori infected children in a periurban community in Bangladesh. METHODS: Twenty-four infants, 4-29 months old (mean age 16.5+/-7.7 months) and infected with H. pylori, were treated with purified immunoglobulins from hyperimmune bovine colostrum for 1 month, in a placebo-controlled, double-blind pilot study. Diagnosis was established with 13C-urea breath test (UBT) before and after the treatment period and at a 1-month follow-up. RESULTS: None of the hyperimmune bovine colostrum-treated children became UBT negative. Five children initially positive in the UBT screening spontaneously became negative by the start of the study with hyperimmune bovine colostrum/placebo. At the end of the 1-month study period, three had became positive again. CONCLUSION: Hyperimmune bovine colostrum does not eradicate H. pylori infection in infants. Transient H. pylori infection is common among infants in high endemic areas, as is reinfection after clearance. This presents obstacles to evaluation of therapeutic investigations in young children in areas where H. pylori is prevalent.

Animals↗
PubMed1998

Induction of unresponsiveness against IgA in IgA-deficient patients on subcutaneous immunoglobulin infusion therapy.

Patients with IgA deficiency often demonstrate circulating antibodies against IgA, which have been suggested to be associated with transfusion reactions. Sera from three patients with common variable immunodeficiency (CVID) and one with a selective IgA deficiency with anti-IgA antibodies receiving subcutaneous gammaglobulin replacement therapy were analysed for serum levels of IgG, IgA and anti-IgA before and during a treatment period of 4-7 years. Treatment with gammaglobulin preparations containing significant amounts of IgA (< 5 mg/ml) resulted in a decrease or disappearance of the anti-IgA antibodies. Analysis of serum fractions, however, revealed anti-IgA activity in the complex-containing fractions. In vitro experiments gave similar results with a shift of anti-IgA activity from the monomeric to the complex-containing fractions (that could not be detected in whole serum). When the patients were subsequently switched to treatment with a preparation containing less IgA (< 80 microg/ml) or made an interruption in the treatment schedule, the anti-IgA antibodies reappeared. Importantly, however, one of the patients lost his anti-IgA activity during a 3-month period on the preparation containing the higher IgA levels, and these antibodies did not reappear after switching to the low IgA-containing preparation. After 5 years on this preparation, anti-IgA can still not be detected, suggesting induction of unresponsiveness.

Adult↗