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L Hammarström

Publications and source records attributed to L Hammarström.

At least 37 records · Page 2Linked to original sources
PubMed2001

Randomized, placebo-controlled, clinical trial of hyperimmunized chicken egg yolk immunoglobulin in children with rotavirus diarrhea.

BACKGROUND: Hyperimmunized bovine colostrum containing antibodies has been shown to be effective in the treatment of rotavirus diarrhea. Antibodies derived from eggs of immunized hens may be a less expensive and more practical alternative. In this study, children with proven rotavirus diarrhea were treated with immunoglobulin extracted from eggs of chicken immunized with human rotavirus strains. METHODS: In a randomized, double-blind study, 79 children with known rotavirus diarrhea were assigned to receive either 10 g hyperimmune egg yolk (HEY) daily in four equally divided doses for 4 days (HEY group) or a similar preparation obtained from nonimmunized chicken (placebo group). The daily stool frequency and amount, oral rehydration solution iORS) intake, and presence of rotavirus in the stool were monitored for 4 days. RESULTS: In the HEY-treated group, there was significant reduction in stool output (in grams per kilogram per day; HEY vs. placebo; 87+/-59 vs. 120+/-75, P = 0.03), and significant reduction of ORS intake (in milliliters per kilogram per day) (HEY vs. placebo; 84+/-46 vs. 122+/-72, P = 0.008) on day 1 and clearance of virus on day 4 (HEY vs. placebo; 73% vs. 46%, P = 0.02). There was, however, no difference in diarrheal duration between the groups. CONCLUSIONS: Treatment with HEY against four human rotavirus strains resulted in modest improvement of diarrhea associated with earlier clearance of rotavirus from stools. These results indicate an encouraging role of HEY in the treatment of rotavirus-induced diarrhea in children. Further studies are needed to optimize the dose and neutralization titer and thus improve the efficacy of egg yolk immunoglobulin IgY derived from immunized hens.

Animals↗
PubMed2001

Enamel matrix derivative promotes reparative processes in the dental pulp.

During odontogenesis, amelogenins from the preameloblasts are translocated to differentiating odontoblasts in the dental papilla, suggesting that amelogenins may be associated with odontoblast changes during development. In the present study, we have explored the effects of enamel matrix derivative (EMD) on the healing of a pulpal wound. Coronal pulp tissue of permanent maxillary premolars of miniature swine were exposed through buccal class V cavities. The exposed pulp was capped with EMD. The contralateral teeth served as controls and were capped with a calcium hydroxide paste (Dycal). The cavities were sealed with glass-ionomer cement. After 2 and 4 weeks, the histology of the teeth was analyzed. In the EMD-treated teeth, large amounts of newly formed dentin-like hard tissue with associated formative cells outlined the pulpal wound separating the cavity area from the remaining pulp tissue. Inflammatory cells were present in the wound area but not subjacent to the newly formed hard tissue. Morphometric analysis showed that the amount of hard tissue formed in EMD-treated teeth was more than twice that of the calcium-hydroxide-treated control teeth (p < 0.001), suggesting that EMD is capable of promoting reparative processes in the wounded pulp more strongly than is calcium hydroxide.

Animals↗
PubMed2000

Relative neutralizing activity in polyspecific IgM, IgA, and IgG preparations against group A streptococcal superantigens.

In this study we compared the ability of different immunoglobulin (Ig) preparations containing IgG, IgM, and/or IgA to neutralize the activity of streptococcal pyrogenic exotoxin A (SpeA) or culture supernatant from a clinical group A streptococcal isolate. All Ig preparations markedly inhibited the mitogenic and cytokine-inducing activity of SpeA and culture supernatant at concentrations of 0.05-0.5 mg/mL, and at 0.5 mg/mL, most caused 95-100% inhibition of both stimuli. A significantly higher (P< or =.05) inhibition of SpeA was achieved by Pentaglobin (IgG, IgM, and IgA) and IgAbulin (IgA and IgG), as compared with pure IgG preparations. IgM- and IgA-enriched preparations had significantly higher inhibitory activity against SpeA than against culture supernatant, whereas the reverse was true for the IgG preparations (P< or =.05). The data show that IgM and IgA are potent inhibitors of specific streptococcal superantigens. These findings may have implications for the optimization of immunotherapy in invasive streptococcal infections.

Culture Media, Conditioned↗
PubMed2000

Impaired antibody affinity maturation process characterizes a subset of patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is an heterogeneous syndrome characterized by decreased levels of serum Ig and recurrent bacterial infection. Here, we were interested to study whether a qualitative defect of the affinity Ab maturation process could be combined to the low level of serum Ig in a cohort of 38 CVID patients. For this, we designed a novel and rapid screening test for the detection of hypomutated V gene expressed by memory B cells. This test delineated a subset of 9/38 (23%) CVID patients with an abnormal pattern of Ig V gene mutation. The mean frequency of V gene mutation of this subset was significantly lower (1.74%) compared with other CVID patients (5.46%) and normal donors (6.5%) (p<0.0001). The mean age of this subgroup was significantly higher than other hypogammaglobulinemic patients with normal levels of V gene mutation (p<0.02), whereas no difference in the duration of symptoms was noted between the two groups. This suggests that hypomutation characterizes patients who began CVID late in life. Recently, it was shown that non-Ig sequences, such as the intronic BCL-6 gene, could be the target of the somatic hypermutation process in normal memory B cells. Our finding of a normal mutation frequency of the BCL-6 gene in two hypomutated CVID point to a defect of the Ig targeting of hypermutation machinery in these cases.

Adult↗
PubMed2000

[Ataxia-telangiectasia surveyed in Sweden].

Ataxia-telangiectasia (AT) is a rare autosomal recessive disease with a complex phenotype involving cerebellar degeneration, immunodeficiency, cancer risk and radiosensitivity. Our aim has been to identify Swedish AT patients in order to study the possible "Swedish phenotype" of the disease. In the 19 patients identified in Sweden we found a phenotype fairly similar to what has been described internationally, with the exception of some differences including lower cancer incidence in patients and their relatives and somewhat more pronounced immunodeficiency and concomitant susceptibility to infections.

Adolescent↗
PubMed2000

Regulation of germline promoters by the two human Ig heavy chain 3' alpha enhancers.

The human IgH 3' enhancers, located downstream of each of the two Calpha genes, modulate germline (GL) transcription of the IgH genes by influencing the activity of promoter-enhancer complexes upstream of the switch and intervening (I) regions. The regulation of GL alpha1 and alpha2 promoters by different human 3' enhancer fragments was investigated in cell lines representing various developmental stages. Both alpha1HS1,2 and alpha2HS1,2 fragments show equally strong enhancer activity on the GL alpha1 and alpha2 promoters in both orientations when transiently transfected into a number of mature B cell line (DG75, CL-01, and HS Sultan). However, there is no activity in a human pre-B cell line (NALM-6) nor a human T cell line (Jurkat). HS3 shows no enhancer activity by itself in any of the cell lines, whereas a modest effect is noted using HS4 in the three mature B cell lines. However, the combination of the alpha2HS3-HS1,2-HS4 fragments, which together form a potential locus control region, displays a markedly stronger enhancer activity than the individual fragments with a differential effect on the alpha1 and alpha2 promoters as compared with the gamma3 promoter. Our results suggest that the human GL alpha promoter may be regulated by two independent pathways. One pathway is induced by TGF-beta1 which directs IgA isotype switch through activation of the GL alpha promoter and no TGF-beta1-responsive elements are present in the different 3' enhancer fragments. The other route is through the human 3' enhancer regions that cis-up-regulate the GL alpha promoter activity in mature B cells.

3' Untranslated Regions↗
PubMed2000

Fine mapping of IGAD1 in IgA deficiency and common variable immunodeficiency: identification and characterization of haplotypes shared by affected members of 101 multiple-case families.

To limit the region containing a mutation predisposing to selective IgA deficiency (IgAD) and common variable immunodeficiency (CVID), 554 informative members of 101 multiple-case families were haplotyped at the IGAD1 candidate locus in the MHC. Microsatellite markers were placed onto the physical map of IGAD1 to establish their order and permit rapid haplotype analyses. Linkage analysis of this extended family set provided additional support for a strong susceptibility locus at IGAD1 with a maximum multipoint nonparametric linkage score in excess of 3. Although the transmission of maternal IGAD1 haplotypes from unaffected heterozygous parents to the affected offspring was in excess, this was not apparent in multiple-case families with a predominance of affected mothers, suggesting that this parental bias is influenced by the affection status of transmitting parents and supporting a maternal effect in disease susceptibility. Of 110 haplotypes shared by 258 affected family members, a single haplotype (H1) was found in 44 pairs of affected relatives, accounting for the majority of the IGAD1 contribution to the development of IgAD/CVID in our families. The H1 allelic variability was higher in the telomeric part of the class III region than in the distal part of the class II region in both single- and multiple-case families. Incomplete H1 haplotypes had most variant alleles in the telomeric part of the analyzed region in homozygous IgAD/CVID patients, whereas this was not observed in unaffected homozygotes. These data suggest that a telomeric part of the class II region or centromeric part of the class III region is the most likely location of IGAD1.

Alleles↗
PubMed2000

Cloning and characterization of the bovine MHC class I-like Fc receptor.

In the cow, maternal immunity is exclusively mediated by colostral Igs, but the receptor responsible for the IgG transport has not yet been identified. The role of an IgG-Fc receptor (FcRn) that resembles a class I MHC Ag in transporting IgGs through epithelial cells was recently shown in selected species. We now report the cloning and characterization of the bovine FcRn (bFcRn). The cDNA and deduced amino acid sequences show high similarity to the FcRn in other species, and it consists of three extracellular domains, a hydrophobic transmembrane region, and a cytoplasmic tail. Despite the high similarity of the extracellular domains with other species, the bovine cytoplasmic tail is the shortest thus far analyzed. Aligning the known FcRn sequences, we noted that the bovine protein shows a 3-aa deletion compared to the rat and mouse sequences in the alpha1 loop. Furthermore, we found a shorter transcript of the bFcRn reflecting an exon 6-deleted mRNA, which results from an inadequate splice acceptor site in intron 5 and produces a transmembrane-deficient molecule, as was previously demonstrated in the related MHC class I gene family in mouse and humans. The presence of bFcRn transcripts in multiple tissues, including the mammary gland, suggests their involvement both in IgG catabolism and transcytosis.

Amino Acid Sequence↗
PubMed2000

Towards an artificial model for Photosystem II: a manganese(II,II) dimer covalently linked to ruthenium(II) tris-bipyridine via a tyrosine derivative.

In order to model the individual electron transfer steps from the manganese cluster to the photooxidized sensitizer P680+ in Photosystem II (PS II) in green plants, the supramolecular complex 4 has been synthesized. In this complex, a ruthenium(II) tris-bipyridine type photosensitizer has been linked to a manganese(II) dimer via a substituted L-tyrosine, which bridges the manganese ions. The trinuclear complex 4 was characterized by electron paramagnetic resonance (EPR) and electrospray ionization mass spectrometry (ESI-MS). The excited state lifetime of the ruthenium tris-bipyridine moiety in 4 was found to be about 110 ns in acetonitrile. Using flash photolysis in the presence of an electron acceptor (methylviologen), it was demonstrated that in the supramolecular complex 4 an electron was transferred from the excited state of the ruthenium tris-bipyridine moiety to methylviologen, forming a methylviologen radical and a ruthenium(III) tris-bipyridine moiety. Next, the Ru(III) species retrieved the electron from the manganese(II/II) dimer in an intramolecular electron transfer reaction with a rate constant kET > 1.0 x 10(7) s(-1), generating a manganese(II/III) oxidation state and regenerating the ruthenium(II) photosensitizer. This is the first example of intramolecular electron transfer in a supramolecular complex, in which a manganese dimer is covalently linked to a photosensitizer via a tyrosine unit, in a process which mimics the electron transfer on the donor side of PS II.

2,2'-Dipyridyl↗
PubMed2000

Regulation of the promoter for human immunoglobulin gamma3 germ-line transcription and its interaction with the 3'alpha enhancer.

The mechanism underlying the differential regulation of switching to human IgG subclasses is still largely unknown. We demonstrate that the region upstream of the initiation sites for gamma3 germ-line (GL) transcripts contains a functional promoter which is synergistically induced by IL-4, antibody to CD40 and phorbol dibutyrate in transient transfection assays in the human DG75 cell line. Linker-scanning mutations identified multiple elements in the 3' half of the evolutionarily conserved sequence that are required for inducibility. Electrophoretic mobility shift assays showed that Stat6 and NF-kappaB p50 / p65 are induced after stimulation, and bind to specific sequence motifs within the promoter. Overexpression of Stat6, NF-kappaB p50 / p65 and C / EBPgamma synergistically induced the GL gamma3 promoter. Insertion of DNA segments from the human 3' IgH regions, which may function as a locus control region for switch recombination, greatly activated the promoter in an orientation-independent manner. Duplication of the enhancer fragments resulted in a further increase of promoter activity. The greater enhancement of the HS1,2 fragment from the 3' alpha1 rather than the alpha2 locus may suggest a mechanistic explanation for the differential expression of various isotypes.

B-Lymphocytes↗
PubMed2000

Characterization of ATM mutations in 41 Nordic families with ataxia telangiectasia.

The Ataxia Telangiectasia Mutation (ATM) gene is mutated in the rare recessive syndrome Ataxia Telangiectasia (AT), which is characterized by cerebellar degeneration, immunodeficiency, and cancer predisposition. In this study, 41 AT families from Denmark, Finland, Norway, and Sweden were screened for ATM mutations. The protein truncation test (PTT), fragment length and heteroduplex analyses of large (0.8-1.2 kb) cDNA fragments were used. In total, 67 of 82 (82%) of the disease-causing alleles were characterized. Thirty-seven unique mutations were detected of which 25 have not previously been reported. The mutations had five different consequences for the ATM transcript: mutations affecting splicing (43%); frameshift mutations (32%); nonsense mutations (16%); small in-frame deletions (5%); and one double substitution (3%). In 28 of the probands mutations were found in both alleles, in 11 of the probands only one mutated allele was detected, and no mutations were detected in two Finnish probands. One-third of the probands (13) were homozygous, whereas the majority of the probands (26) were compound heterozygote with at least one identified allele. Ten alleles were found more than once; one Norwegian founder mutation constituted 57% of the Norwegian alleles. Several sequence variants were identified, none of them likely to be disease-causing. Some of them even involved partial skipping of exons, leading to subsequent truncation of the ATM protein.

Alternative Splicing↗
PubMed2000

An allotype-associated polymorphism in the gamma3 promoter determines the germ-line gamma3 transcriptional rate but does not influence switching and subsequent IgG3 production.

The human IgG3 (b) allotype is associated with a high and the (g) allotype with a low mean serum level of IgG3 which is due to a low frequency of B cell switching in the latter. In the present study, we found a polymorphism in position -73 (C --> A), located in the 4th NF-kappaB site of the germ-line (GL) gamma3 promoter, resulting in a significant decrease of both the basal and induced activity in the (g) allotype-associated promoter. Over-expression experiments also showed that this polymorphism reduced the synergistic activation of the promoter by Stat6 + NF-kappaB p50 / p65 or Stat6 + C / EBPgamma. A low level of GL gamma3 transcripts was also observed in individuals carrying the (g) allotype-associated promoter region. However, an individual homozygous for a crossover between the promoter and switch region, i. e. with a (g) allotype-associated promoter and a (b) allotype-associated switch region, showed a normal level of switching and IgG3 serum level. This suggests that although the (g) allotype-associated promoter is functionally inferior to that of the (b) allotype-associated promoter, these differences do not affect switching and final production of IgG3 and that polymorphisms in the switch region are more important in controlling this process.

B-Lymphocytes↗
PubMed2000

Emdogain--periodontal regeneration based on biomimicry.

Biomimicry has been introduced as a term for innovations inspired by nature [1]. Such innovations may appear in almost every part of modern society. This review on the effects of enamel matrix proteins on the formation of cementum and the development of emdogain for regeneration of periodontal tissues lost due to periodontitis shows an example of biomimicry in dentistry. Findings from clinical and laboratory investigations are summarized and the biological basis for enamel matrix-induced periodontal regeneration is discussed.

Chemistry, Pharmaceutical↗
PubMed2000

Tissue responses to natural aragonite (Margaritifera shell) implants in vivo.

The purpose of this study was to access tissue reactions to the outer prismatic (prism) and the inner nacreous (nacre) layers of the fresh water Margaritifera shell. The materials, in granule form, were implanted into the back muscles and femurs of rats for 1, 2, 4, 8 and 16 weeks. In the back muscles, a foreign body reaction was observed around the implants, starting from one week after implantation and reaching maximal proportions at two weeks. After four weeks, a thin layer of fibrous tissue encapsulated the implanted particles. The external surface of the material stained strongly with acid fuchsin, indicating degradation of implant. At femoral sites, newly formed bone was directly applied to the implant surfaces. The outer-most parts of the organic sheets in prisms were not degraded until 16 weeks after implantation and were embedded in the newly formed bone. The interface between bone and the implants showed close fusion by scanning electron microscopy (SEM). Energy dispersive X-ray analysis (EDAX) demonstrated a phosphorous-rich zone in the interface between bone and the implants, and no electron-dense layer in the interface was found by transmission electron microscopy (TEM). We conclude that Margaritifera shells are biocompatible, biodegradable and osteoconductive materials. Bonding between this natural aragonite and bone seems to occur via a phosphorous-rich intermediate layer.

Animals↗
PubMed2000

Molecular basis of IgG subclass deficiency.

IgG subclass deficiency was recognized as a separate disease entity in the early seventies and was shown to be associated with an increased susceptibility to infections. Although deletions of the corresponding gamma genes have been demonstrated in a few cases, a majority of patients suffer from a regulatory dysfunction, and the deficiencies are most often relative rather than absolute. Some of the molecular mechanisms underlying the disorder have been unraveled recently. In this review we will touch upon the deletions described within the IGHC locus but mainly concentrate on the regulatory aberrations involved in IgG subclass deficiency.

Gene Deletion↗
PubMed2000

Autologous T lymphocytes recognize the tumour-derived immunoglobulin VH-CDR3 region in patients with B-cell chronic lymphocytic leukaemia.

We have previously shown that autologous T cells recognize leukaemic cells from patients with chronic lymphocytic leukaemia (B-CLL) in an MHC class I- and/or II-restricted manner. A candidate recognition structure might be the tumour cell-derived Ig VH complementarity-determining region (CDR)3. Three patients with B-CLL were analysed for the presence of autologous T cells recognizing the tumour-specific VH-CDR3 region. The VH region was shown to be mutated in all three patients. In two patients, a VH-CDR3-specific T-cell response was detected by proliferation assay, as well as by gamma-interferon (IFN) production. The responses could be inhibited by monoclonal antibodies against MHC class II, but not MHC class I. In the third patient, a VH-CDR3 proliferative response was detected, which could be inhibited by an anti-MHC class I monoclonal antibody, but not by anti-MHC class II antibodies. No gamma-IFN response could be detected in this patient. In no patient was an interleukin (IL)-4 response noted. Thus, in patients with B-CLL, naturally occurring T cells recognizing the tumour-unique VH-CDR3 region are present.

Aged↗
PubMed2000

Children with recurrent episodes of acute otitis media: the effect of local administration of immunoglobulin G on acute otitis media, colonization and turnover of non-encapsulated Haemophilus influenzae in the nasopharynx.

In most children with recurrent episodes of acute otitis media (AOM), tube treatment is successful, but there are those who nevertheless suffer from middle ear infections. The aim of the present study was to ascertain whether local administration of immunoglobulin could reduce the number of episodes of otorrhoea in otitis-prone infants <2 years old who were treated with tubes, or whether it could affect the nasopharyngeal colonization and turnover of bacterial pathogens in the nasopharynx. IgG or placebo were also administered intranasally daily for 6 months to 50 infants, randomized in a double-blind study. An arbitrarily primed polymerase chain reaction (AP-PCR) was used to characterize the different isolates of NTHI (non-encapsulated, non-typable Haemophilus influenzae). Three infants in the IgG group and six infants in the control group suffered from > or =3 episodes of acute otitis media. No effect on the nasopharyngeal colonization or the turnover of non-encapsulated H. influenzae in the nasopharynx could be detected in either group.

Acute Disease↗