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Biomedical subjects

L Hammarström

Publications and source records attributed to L Hammarström.

At least 181 records · Page 10Linked to original sources
PubMed1991

Home treatment of hypogammaglobulinaemia with subcutaneous gammaglobulin by rapid infusion.

Intramuscular and intravenous gammaglobulin treatment for hypogammaglobulinaemia is often associated with systemic adverse reactions in some patients. Subcutaneous infusions of gammaglobulin are usually given at a slow rate. To assess the safety of home treatment with subcutaneous gammaglobulin, rapid infusions (34-40 ml/h) given by small portable pumps were used to treat twenty-five patients with hypogammaglobulinaemia. Fifteen patients had previously had adverse reactions to intramuscular or intravenous gammaglobulin treatment. After the patients had been taught how to use the pumps during 6 months of treatment in hospital, in which they initially received 100 mg of an intramuscular gammaglobulin preparation/kg per week, they went on to use the pumps at home or at work. So far, the patients have given themselves 3232 rapid subcutaneous infusions (2308 in home therapy). A median pre-infusion serum IgG concentration of 8.1 g/l resulted after 6 months of treatment. There were only 30 (0.93%) mild systemic adverse reactions; there were fewer reactions with subcutaneous gammaglobulin than with previously given intramuscular injections (n = 21, p less than 0.001) or intravenous infusions (n = 9, p less than 0.001) in this group of patients. Overall, the patients spent 0.2 days a year in hospital due to respiratory tract infections. The findings show that the method for subcutaneous administration is very easy to learn and is appreciated by the patients; moreover, the infusions can be given much faster than previously reported without any pronounced local reaction.

Adolescent↗
PubMed1991

Antigenicity of mouse monoclonal antibodies. A study on the variable region of the heavy chain.

Mouse monoclonal antibodies (Mabs) against human tumour antigens are currently used in therapy, but up to 50% of the patients receiving treatment form anti-Mab antibodies thus reducing the efficiency of the treatment. One attempt to minimize the immunogenicity of the mouse Mabs is to "humanize" them by replacing the constant part of the molecule with the human equivalent by genetic engineering. However, this does not reduce the immunogenicity of the variable part of the antibody. Some variable regions may be expected to be less antigenic than others. We therefore compared consensus sequences for the 11 mouse VH families with the human VH sequences published so far. Theoretical antigenicity predictions (hydrophilicity, flexibility, surface accessibility and relative antigenicity) were made and two families; VH I(J558) and VH XI (CP5 B5-3) were predicted to be immunogenic by all four methods. One family, VH X (MRL-DNA4), was not predicted to be immunogenic by any of the four methods. The residues predicted to form antigenic epitopes in the two families VH II (Q52) and VH III (36-60) are predicted not to be exposed on the surface of the antibody molecule and may therefore not be immunogenic.

Animals↗
PubMed1991

Biological half-life of normal and truncated human IgG3 in scid mice.

The fractional catabolic rate of IgG in the body is regulated with precision in order to maintain appropriate serum concentrations. We have investigated the turnover rate of normal human IgG3, a newly identified, naturally occurring, truncated form of IgG3 and a human-mouse chimeric IgG3 antibody in an immunodeficient mouse strain, C.B-17 (SCID), lacking endogenous Ig. The half-life of non-truncated, normal serum IgG3 as well as the chimeric antibody was about 7 days, whereas truncated IgG3 had a shorter half-life of about 5 days. Due to the inherent immune defect, the SCID mouse could represent a versatile animal model for the determination of turnover rates, inasmuch as an immune response will not be mounted against foreign antigens.

Animals↗
PubMed1991

Anti-IgA antibodies in epileptic patients with a low serum IgA concentration.

Sera from 22 phenytoin-treated epileptic patients with a serum IgA less than 0.30 g/l were examined for anti-IgA antibodies using an ELISA. Only one patient had a complete IgA deficiency. Anti-IgA antibodies of restricted specificity were detected in serum from two of the patients. Their serum IgA concentrations were 0.03 and 0.27 g/l. The serum concentrations of IgM, IgG and the IgG subclasses were normal in both these patients. The frequency of this type of anti-IgA antibody is not higher in epileptic patients with a low serum IgA than in healthy controls, and class-specific anti-IgA antibodies are not a pathogenetic factor in the IgA deficiency occurring in epilepsy.

Antibodies, Anti-Idiotypic↗
PubMed1991

Osteoclasts: structure and function.

Osteoclasts are multinucleated giant cells showing specialized membrane structures, clear zones and ruffled borders, which are responsible for the process of bone resorption. These cells arrive at the resorption site via the bloodstream as mononuclear cells, derived from haemopoietic precursors in the spleen or bone marrow, which fuse prior to resorption. The osteoclast may share an early progenitor cell, the granulocyte macrophage colony-forming unit (GM-CFU) with monocytes, macrophages and granulocytes, implying that osteoclasts share the pluripotent haemopoietic stem cell with all other haemopoietic cells. In the past, elucidation of the structure of these cells relied upon traditional ultrastructural techniques. Transmission electron microscopic studies revealed details of the unique ultrastructure of these cells and, in combination with stereological techniques, showed the response of cells to various hormonal stimuli. Scanning electron microscopy not only demonstrated the surface appearance of osteoclasts, and their predilection for spreading on various substratum components, but has also been used as an adjunct in resorption assays in which areas of resorption lacunae are measured as indicators of cell activity. Recent advances in fields such as immunocytochemistry and freeze fracture techniques have contributed towards a more detailed delineation of antigenic profile, cytoskeletal structure and localization of enzymatic pathways. The osteoclast is subject to extensive regulatory mechanisms and it has been established that the osteoblast plays a major rôle in mediating the effects of osteotropic hormones and local mediators on these cells. Hence, research aimed at elucidating the coupling mechanisms between these two cells may result in new therapies for bone disease.

Animals↗
PubMed1991

The effects of pregnancy and fluoride on orthodontic tooth movements in rats.

The present investigation was undertaken in order to study the velocity of orthodontic tooth movement in rats and the effect of the hormonal changes that occur during pregnancy or with fluoride, which is one of several trace elements that affect hard tissue metabolism. Adult, female Sprague-Dawley rats were separated into three groups: non-pregnant, pregnant, and non-pregnant NaF-supplied. All rats were treated with a fixed orthodontic appliance which moved the upper first molars in a buccal direction during 21 days. The appliances delivered an initial force of 150 mN. Repeated intra-oral, standardized radiographs were taken during the experimental period, and at the end of the experiment the maxillae were examined histologically. The velocity of tooth movement was calculated after measurement of the radiographs. The first molars were moved in a buccal direction in all groups. The mean value of the expansion from day 0 to 21 was significantly higher among the pregnant rats (0.64 mm) compared to the non-pregnant, control animals (0.46 mm) while the NaF-supplied rats had a significantly lower expansion (0.22 mm) compared to the control animals. In the histological examination of the pressure sides of the PDL of the upper first molars, the mean value of osteoclasts per microns x 10(-3) increased non-significantly in the group of pregnant rats and decreased significantly among the NaF-supplied animals compared to the non-pregnant control rats. The present experiment in rats indicated that the velocity of orthodontic tooth movement is influenced by hormones as well as trace elements.

Alveolar Bone Loss↗
PubMed1991

TGF-beta 1 induces germ-line transcripts of both IgA subclasses in human B lymphocytes.

Immunoglobulin (Ig) class switching appears to be preceded by induction of germ-line transcripts. In this report, we demonstrate that transforming growth factor beta (TGF-beta) induces germ-line transcripts of both the IgA subclasses (IgA1 and IgA2) in Branhamella catarrhalis (BC)-activated human spleen B cells. Two germ-line bands, one of approximately 1.85 kb and the other of approximately 1.6 kb, could be seen in cultures treated with TGF-beta. The approximately 1.85 kb band contains mRNA for a germ-line transcript of the membrane form. This band co-migrates with the productive secreted form of alpha mRNA. The other, shorter form of approximately 1.6 kb did not correlate in size with any known form of productive alpha mRNA and contained the secreted form of germ-line alpha mRNA. The induction of alpha germ-line transcripts was accompanied by a concomitant suppression of mu and gamma mRNA. We have also identified the location of a putative I alpha sequence (designated according to the generally accepted nomenclature) within approximately 0.5 kb upstream to the switch alpha (S alpha) region. The relative proportions of IgA-subclass-specific mRNA in TGF-beta-stimulated spleen B cells are concordant with the distribution pattern seen in pokeweed mitogen (PWM)-stimulated spleen mononuclear cells (MNC), which was 89 and 11% for the IgA1 and the IgA2 mRNA respectively. These results suggest a role of TGF-beta in regulating IgA class switching in human B lymphocytes.

B-Lymphocytes↗
PubMed1991

Structure of TGF-beta 1-induced human immunoglobulin C alpha 1 and C alpha 2 germ-line transcripts.

We have characterized the structure of the human immunoglobulin C alpha 1 and C alpha 2 germ-line transcripts that are synthesized upon treatment of human B lymphocytes with Branhamella catarrhalis (a B cell mitogen) and transforming growth factor beta 1 (TGF-beta 1). These transcripts initiate upstream of the switch alpha 1 and switch alpha 2 regions and contain, together with the C alpha 1 and C alpha 2 sequences, additional exons designated according to the generally accepted nomenclature I alpha 1 and I alpha 2 respectively. The I alpha exons are spliced directly onto the acceptor splice site of the CH1 domains of the C alpha 1 and C alpha 2 genes. As in other previously characterized germ-line transcripts, stop codons present in all three reading frames prevent translation of the C alpha 1 and C alpha 2 heavy-chain coding sequences. The longest open reading frame (ORF) present in the I exons can code for a polypeptide of only 26 amino acids. The human I alpha exons do not show any significant sequence homology with the corresponding mouse I alpha exon. However, comparison of nucleotide sequences of the genomic mouse and human I alpha regions demonstrated the presence of an approximately 300 bp highly conserved element located immediately upstream of the transcription initiation sites of the human and mouse C alpha germ-line transcripts. The isolation of the C alpha 1 and C alpha 2 germ-line transcripts will further facilitate the characterization of the molecular events responsible for the regulation of the human C alpha heavy chain loci.

Base Sequence↗
PubMed1991

Quantitative and qualitative analysis of human IgG subclass specific mRNA using solution hybridization.

Four IgG subclasses have been identified in the human system. Despite the fact that they exhibit differences in their functional properties, antigenic properties and chemical composition and demonstrate age-related shifts in their expression, the genes coding for their constant regions show extensive homology at the nucleotide level (greater than 95%). The only parts of the C gamma genes that show significant variation among the different IgG subclasses are the exons coding for their hinge regions (less than 60%). Taking advantage of such sequence variation, we have developed specific RNA probes which allowed us to analyse the expression of the C gamma 1, C gamma 2, C gamma 3 and C gamma 4 genes at the mRNA level using solution hybridization. We have defined optimal conditions that allow the detection of picogram levels of IgG subclass specific mRNA, while keeping the cross-reactivity between the different probes below 2%. This approach will significantly facilitate studies aiming at characterizing the molecular mechanisms regulating the expression of the four human IgG heavy chain constant region genes.

Base Sequence↗
PubMed1991

C4 polymorphism and major histocompatibility complex haplotypes in IgA deficiency: association with C4A null haplotypes.

IgA-deficient individuals (n = 110) and six families comprising 9 cases of IgA deficiency were typed for HLA-A, -B, -DR, C4 and factor B. Phenotype frequencies were increased for HLA-B8 (p = 0.004), HLA-DR3 (p = 0.001) and homozygous C4AQ0 (p = 0.01) and decreased for HLA-B7 (p = 0.004), HLA-DR2 (p = 0.0001) and C4A3 (p = 0.00007) compared to controls. Homozygous C4A deficiency was found in 20% of IgA-deficient persons. As clearly suggested by investigation of families, the findings could be attributed to high prevalence of the extended major histocompatibility complex (MHC) haplotype [HLA-A1, B8, C4AQ0, C4B1, BfS, DR3] in IgA deficiency. All but 1 of the 9 IgA-deficient persons included in the family study carried this haplotype and 4 of them were homozygous. In the families, 3 persons with normal serum IgA concentrations had the same MHC haplotypes as their IgA-deficient relatives. The findings were also consistent with possible overrepresentation of other MHC haplotypes with aberrant C4 gene organization in IgA deficiency. As previously suggested, the presence of two MHC haplotypes associated with IgA deficiency appears to be a necessary but not sufficient requirement for manifestation of the condition. The putative existence of a recessive gene in the MHC with regulatory function with regard to IgA gene expression is consistent with the findings.

Complement C4↗
PubMed1991

Mineralization disturbances of the developing rat molar induced by mono- and bisphosphonates.

Morphological changes have been reported previously in the developing dental tissues of the rat molar following administration of mono- or bisphosphonates. However, few studies have been published on the relationship between these and the possible mineralization disturbances. Two monophosphonates, phosphonoformic and phosphonoacetic acids, and two bisphosphonates, dichloromethylene bisphosphonate (Cl2MBP) and 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) in a dosage of 10-30 mg P/kg b.w. were injected in 5 day old rats and the induced changes analyzed by microradiographic and histologic examination. A single injection of mono- or bisphosphonates resulted in apparently identical disturbances of the developing enamel associated with subameloblastic cysts. Three different types of cysts were distinguished. In type 1 cysts, enamel hypoplasia near the cusp tip with an outer highly mineralized zone associated with calcified deposits in the cystic lining and inner hypomineralized enamel were discerned. The type 2 cysts were characterized by the formation of a thick enamel layer in the cervical area and deep in the fissures due to the development of internal enamel defects. The type 3 cysts were seen in the cervical area of the mesial or distal sides of the tooth without any remarkable changes in the underlying enamel matrix. Both Cl2MBP and HEBP induced two demarcation lines in the dentin layer. Additionally, HEBP resulted in the formation of niche-like defects of unmineralized dentin which healed by mineral deposition from the periphery. From these results, it can be concluded that mono- and bisphosphonates have similar effects on enamel mineralization and the type of response depends on the stage of enamel matrix secretion while bisphosphonates, in addition, interfere with the dentin mineralization.

Alveolar Process↗
PubMed1991

Gene deletions in the human immunoglobulin heavy chain constant region locus: molecular and immunological analysis.

Single and extensive multigene deletions have been described in the Ig CH immunoglobulin heavy-chain constant region genes, some of these encompassing up to 160 kilobases. To date six different multigene deletion haplotypes have been identified, designated I to VI according to the chronological order of their findings; deletion I (del G1-EP1-A1-GP-G2-G4), II (del EP1-A1-GP), III (del A1-GP-G2-G4-E), IV (del EP1-A1-GP-G2-G4), V (del GP-G2-G4-E-A2), VI (del G1-EP1-A1-GP-G2). Individuals were found either homozygous for one type of deletion or heterozygous for two different deletions, mainly in the Mediterranean area. The high level of consanguinity in the Tunisian population accounts for the high frequency of individuals homozygous for one or the other of these multigene deletions which involve highly homologous regions as hot spots of recombinations, outside of the switch sequences, in the Ig CH locus. In 15 cases out of 16, these multigene deletions have been observed in healthy people, although these individuals lacked several immunoglobulin subclasses and, even, one class. Such an immunological situation makes it possible to study the importance of these subclasses for the overall immunity, and to analyse the specific immune responses by the retained IgG and IgA subclasses.

Chromosome Deletion↗
PubMed1990

Different amino acids at position 57 of the HLA-DQ beta chain associated with susceptibility and resistance to IgA deficiency.

The human leukocyte antigens (HLA) are implicated in the genetic susceptibility to a large number of diseases. Some of the diseases associated with HLA class II are related to specific amino acids or epitopes of the domain of the HLA class II molecule that is distal to the membrane. In man, selective immunoglobulin A deficiency is the most common immunodeficiency, frequently resulting in recurrent sino-pulmonary infections and gastro-intestinal disorders. Associations have been described with HLA class I, and to a lesser extent with different class II alleles, which might indicate that they share some common feature. Here we study 95 IgA-D patients and find positive associations with three DR-DQ haplotypes and a strong negative association with a fourth haplotype. Comparison of the sequences of the polymorphic amino-terminal domain of the DQ beta chain showed that the three 'susceptibility' haplotypes all had a neutral alanine or valine at position 57. The 'protective' allele had the negatively charged aspartic acid at this position (Asp57). Codon 57 of the HLA-DQ beta chain has been implicated in the susceptibility to insulin-dependent diabetes mellitus. Our data suggest that the same amino acid position could possibly also influence susceptibility and resistance to selective immunoglobulin A deficiency.

Amino Acid Sequence↗
PubMed1990

Subclass distribution of antigen-specific IgA antibodies in normal donors and individuals with homozygous C alpha 1 or C alpha 2 gene deletions.

To analyze the subclass restriction of Ag-specific IgA, sera and saliva from healthy blood donors and from IgA class or subclass deficient individuals were studied. The latter included donors with or without C alpha 1 or C alpha 2 gene deletions. Monoclonal human IgA1 and a genetically engineered IgA2 antibody, normal human serum and colostrum IgA were used as standards to estimate serum and saliva levels of Ag-specific antibodies. In normal individuals, there was a strong IgA1 preference of naturally acquired antibodies in serum against both polysaccharide Ag (PPS 6A, PPS 23, pneumococcal C-polysaccharide, and LPS from Escherichia coli) and protein Ag (Staphylococcus aureus alpha-toxin and HSV). Specific IgA2 in serum against the tested Ag were frequently not measurable. In contrast, most of the individuals with homozygous C alpha 1 gene deletions displayed substantial amounts of specific IgA2 against protein as well as polysaccharide Ag. The median levels of specific IgA in serum against protein Ag were approximately one-third as compared to normal individuals and one-fifth, or less, against polysaccharide Ag. Normal serum levels of IgA against the tested Ag, restricted to the IgA1 subclass, were noted in two individuals with IgA2 deficiency, one of whom carried a homozygous C alpha 2 gene deletion. Median values of specific IgA, against the tested Ag S. aureus alpha-toxin, HSV, and pneumococcal C-poly-saccharide, from normal healthy donors were approximately four to eight times higher in serum as compared to saliva. Individuals with homozygous C alpha 1 gene deletions displayed increased levels of the various specific IgA2 antibodies in saliva. In conclusion, the individuals with homozygous C alpha 1 gene deletions displayed decreased median levels of specific IgA antibodies in serum despite normal levels of total IgA. Normal levels of both specific IgA and total IgA in saliva were found.

Chromosome Deletion↗