PubMed Health⌕ Search

Biomedical subjects

L Hammarström

Publications and source records attributed to L Hammarström.

At least 145 records · Page 8Linked to original sources

Gamma-globulin modulates growth of EBV-derived B-cell tumors in SCID mice reconstituted with human lymphocytes.

The effect of weekly gamma-globulin injection on the development of human B-cell tumors was studied in 120 mice with severe combined immunodeficiency (SCID). The mice were injected intraperitoneally (i.p.) with human peripheral mononuclear cells (PBMC) from 6 different Epstein-Barr virus (EBV)-seropositive donors. Animals repopulated with cells from 5 donors received gamma-globulin or saline for 20 weeks and were followed up to 24 weeks after reconstitution. A delay in the appearance of fata EBV-derived human B-cell tumors was noticed in the gamma-globulin-treated groups as compared to the controls. In a separate experiment, the effect of gamma-globulin treatment during the initial 4 weeks after reconstitution was compared to treatment from week 5 to week 8 as well as to a continuous 20-week treatment. The results from this experiment showed that B-cell tumor growth could be prevented just as efficiently when the animals were treated only during the first 4 weeks. In contrast, no preventive effect was seen when the first gamma-globulin dose was given at the beginning of week 5 after reconstitution. Our results indicate that gamma-globulin reduces the frequency of EBV-derived B-cell tumor development and suggest that SCID mice repopulated with human cells represent a useful in vivo model for evaluation of the prophylactic and/or therapeutic effects of immunomodulatory treatments in lympho-proliferative disorders associated with immunosuppression.

Animals↗

The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases.

X-linked agammaglobulinaemia (XLA) is a human immunodeficiency caused by failure of pre-B cells in the bone marrow to develop into circulating mature B cells. A novel gene has been isolated which maps to the XLA locus, is expressed in B cells, and shows mutations in families with the disorder. The gene is a member of the src family of proto-oncogenes which encode protein-tyrosine kinases. This is, to our knowledge, the first evidence that mutations in a src-related gene are involved in human genetic disease.

Agammaglobulinemia↗

Molecular basis for human immunodeficiencies.

Major emphasis is currently being placed on unraveling the molecular basis of various forms of primary human immunodeficiencies. It is clear from recent studies that not only can different mutations give rise to different phenotypes but the same mutation may result in quite diverse clinical pictures. A correct diagnosis at the DNA level therefore becomes increasingly important in view of the possibility of gene therapy.

Agammaglobulinemia↗

The life situations of patients with primary antibody deficiency untreated or treated with subcutaneous gammaglobulin infusions.

The life situations of 25 patients with hypogammaglobulinaemia were studied before and after the initiation of subcutaneous replacement therapy by using medical records, data registers and questionnaires (a study and a disease-specific questionnaire, the Sickness Impact Profile and the General Health Rating Index). Before treatment, the patients perceived more dysfunctions with regard to ambulation, mobility, emotional behaviour, social interaction, sleep and rest, household management, work and recreation or pastime activities compared with a Swedish reference group (P = 0.0001). A significant increase in the perceived frequency of infections was also seen in untreated patients compared with a group of healthy individuals (P = 0.0001). After 18 months of weekly subcutaneous infusions of an intramuscular gammaglobulin preparation (100 mg/kg), the patients reported a significantly increased, health-related function and improved self-rated health. A significantly higher pre-infusion IgG level was also found.

Adult↗

Systemic immunization against IgA in immunoglobulin deficiency.

The presence of serum IgM and IgG antibodies against IgA is common among individuals with IgA deficiency. The route of immunization is still unknown, but it is possible that immunization occurs through the gut. We analysed anti-IgA antibody production in gastrointestinal lavage, saliva and breast milk from patients with IgA deficiency. In no case was there any evidence of local production of anti-IgA antibodies. Immunization may thus be due to exposure to endogenous IgA and therefore represent a 'true' autoimmune phenomenon which may possibly be involved in the pathogenesis of the disease.

Antibodies, Anti-Idiotypic↗

Novel human immunoglobulin heavy chain constant region gene deletion haplotypes characterized by pulsed-field electrophoresis.

Fifteen patients with selective IgG1 deficiency were screened for immunoglobulin H chain C region locus (IGHC) gene deletions and three deletion haplotypes were found: del G1, del G1-G4 and del G4. These haplotypes, together with four deletion haplotypes described by us previously (del G1 (NY), del G1 (VIT) del G1-G2 (NY) and del G2-G4 (HJE)), were further characterized using pulsed-field gel electrophoresis (PFGE) to determine the physical extent of the deletions. The MluI fragment sizes confirmed the deletions, although the deduced sizes of the most extensive deletions indicated that material had been inserted into the locus.

Electrophoresis, Gel, Pulsed-Field↗

Experimentally induced dentoalveolar ankylosis in rats.

Dentoalveolar ankylosis is a common complication after replantation of teeth with injured periodontal ligaments. This is a serious complication for the tooth since it leads to progressive root resorption. In young individuals it may also cause infra-occlusion and reduced development of the alveolar process. The purpose of this study was to develop a method applicable to rats in order to follow the effect of systemic and local factors on the development of ankylosis and their possible effect on the length of the functional period of the ankylosed tooth before exfoliation. The maxillary first molars in adult rats were extracted. The periodontal ligaments were devitalized or removed before replantation of the teeth. Dentoalveolar ankylosis was clinically established 2 weeks after replantation. Induction was most reproducible after devitalization or removal of the PDL cells with Dakin's solution and after keeping the rats on a liquid diet up to 3 weeks after replantation. Exfoliation of the teeth usually occurred 6 weeks after replantation. Histological examination showed that the PDL was replaced by bone. The ankylosed teeth showed root resorption to a varying degree. The resorption was in some cases occasionally located in the supra-crestal part of the tooth. A bone-like tissue in the root canal was a rather common finding. In one of the ankylosed teeth cartilage formation was found adjacent to the cementum.

Animals↗

A 40-base-pair duplication in the gp91-phox gene leading to X-linked chronic granulomatous disease.

Chronic granulomatous disease (CGD) is characterized by the inability of the patients' phagocytic leukocytes to generate superoxide. Therefore, these cells fail to kill certain bacteria and fungi. As a result, patients with CGD suffer from recurrent, life-threatening infections with these micro-organisms. Superoxide is produced by NADPH oxidase, a multicomponent enzyme exclusively present in phagocytic leukocytes. The most common form of CGD is X-linked, originating from a deficiency of the high-molecular-weight subunit of cytochrome b558 (gp91-phox). Here we describe a patient suffering from X-linked CGD due to a 40-base-pair duplication in exon 7 of the CYBB gene coding for gp91-phox, predicting a frameshift, substitution of 22 amino acids and a premature stop codon at amino-acid position 253. The mother as well as the grandmother of this patient were proven to be heterozygous for this mutation; the father and sister were normal. However, the great-grandmother proved to have normal oxidative functions, suggesting that the mutation occurred three generations ago. This is the first description of a nucleotide duplication leading to CGD.

Amino Acid Sequence↗

Anti pneumococcal antibody activity in nasopharyngeal secretions in healthy adults and children.

The local antibody activity to Streptococcus pneumoniae serotype 6B was measured in nasopharyngeal secretions from 20 healthy adults and 43 children, 1-3 years of age, 14 of whom were healthy and 29 were at risk for developing recurrent episodes of acute otitis media (RAOM) according to the criteria described below. In children, anti pneumococcal IgA and IgG antibody activity was of the same magnitude in both groups. Adults showed significantly higher specific IgA activity. Antibody activity of the IgG isotype was also higher in adults, possibly reflecting the higher serum antibody levels. The children at risk of developing RAOM had significantly higher levels of secretory component (SC) in their nasopharyngeal secretions. Our data suggest that local immunity in the nasopharynx is not fully developed in young children, which might contribute to bacterial survival and colonization in the region.

Acute Disease↗

Nasal administration of IgA to individuals with hypogammaglobulinemia.

Many immunodeficient patients constantly carry non-typable Hemophilus influenzae (NTHI) in the nasopharynx, despite seemingly adequate antibiotic therapy. We have studied the effect of nasal administration of IgA on nasopharyngeal colonization in 5 patients with hypogammaglobulinemia, with a productive cough, especially in the mornings, who were constant carriers of NTHI in the nasopharynx, and had IgA, 1 ml 6 times/day, given nasally for 14 days. Nasopharyngeal cultures were obtained on days 0, 7, 14 and 28. Two of the patients became culture-negative during the treatment, and the cough was alleviated in all patients.

Administration, Intranasal↗

Nasal administration of immunoglobulin as effective prophylaxis against infections in elite cross-country skiers.

15 elite skiers (Swedish olympic team) taking part in the games in Alberville were prophylactically treated with nasal administration of immunoglobulin, mainly IgA. Team coaches served as controls. No infections occurred in the treated group, whereas 9/19 of the coaches developed symptoms of infection. These results suggest that nasal administration of antibodies significantly reduces the incidence of upper respiratory tract infections in elite skiers and may serve as a valuable short-term physiological prophylaxis in the prevention of disease.

Administration, Intranasal↗

Isolation of cDNA clones mapping around DXS178: a search for human X-linked agammaglobulinaemia gene using yeast artificial chromosomes, cosmids and direct cDNA selection.

X-linked agammaglobulinaemia (XLA) was previously mapped using genetic linkage analysis to Xq22. No recombinants have been found so far between the XLA locus and DXS178 in over 30 informative meioses. Two overlapping yeast artificial chromosomes (YACs), which cover a region of approximately 1000 kb around DXS178 and form part of a larger YAC contig, were hybridised to an ordered cosmid library constructed from a human fibroblast cell line with karyotype 49,XXXXX. Positive cosmids were gridded in high density arrays onto nylon filters and rescreened with a series of YACs, YAC end probes and additional markers from the region to assign cosmids into intervals. A 640 kb-YAC hybridising to p212 (DXS178) was used for direct selection of PCR-amplified cDNA from two cDNA libraries. To identify the cosmids containing transcribed sequences the enriched cDNA from each library was radiolabelled and hybridised back to positive clones which mapped to the region of interest. These clones were then hybridised to the subcloned enriched cDNA sublibraries. Candidate cDNA clones were isolated, grouped within the region of interest and their position was confirmed by mapping back to the cosmids.

Agammaglobulinemia↗