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Biomedical subjects

L Hammarström

Publications and source records attributed to L Hammarström.

At least 73 records · Page 4Linked to original sources
PubMed1998

Characterization of the gene for the membrane and secretory form of the IgM heavy-chain constant region gene (C mu) of the cow (Bos taurus).

Our present understanding of the evolution of immunoglobulins is derived from a few vertebrate species. In order to obtain additional information on the development of the humoral immune system, we cloned and determined the nucleotide sequence of the bovine cDNA and genomic IgM heavy-chain constant region gene (C mu). The gene contains four constant region domain-encoding exons (CH1 to CH4) and two exons encoding the transmembrane domain (TM1, TM2), expressed in the membrane-bound receptor form of the IgM. The sequence of a cDNA clone encoding the 3' portion of the membrane form of the mu-chain revealed that the TM1 exon is spliced to the CH4 exon, as occurs in other mammals. Comparison of deduced amino acid sequence data from different vertebrates revealed a high similarity to sheep C mu (88%) and a lower degree of similarity to pig (62%), rat (62%), rabbit (58%) human (56%), hamster (55%), mouse (54%), chicken (28%) and horned shark (22%) C mu.

Amino Acid Sequence↗
PubMed1998

Intranasally administered immunoglobulin for the prevention of rhinitis in children.

OBJECTIVE: To determine the efficacy of intranasally administered immunoglobulin in preventing symptoms of rhinitis in children. METHODS: Forty children ages 1 to 4 years who attended day-care centers in Turku, Finland, were enrolled in the double blind, placebo-controlled study. The children were randomly assigned to receive treatment with immunoglobulin, composed mainly of immunoglobulin A, or placebo, both administered as nasal sprays twice daily for 8 weeks. During this medication period and an additional 8-week follow-up period, the parents recorded the symptoms of the children daily in the diaries provided. One child who met an exclusion criterion was withdrawn from the study after a few days of medication. RESULTS: During the 8-week medication period the 19 children in the immunoglobulin group had 42% fewer days with rhinitis than the 20 children receiving placebo (mean, 10.8 vs. 18.7 days; P=0.004). The total numbers of episodes of rhinitis in the immunoglobulin and placebo groups were 33 and 51, respectively. No significant differences were observed between the groups during the postmedication follow-up period. CONCLUSIONS: Intranasal administration of immunoglobulin appears to be an effective method to prevent symptoms of rhinitis in children, and further studies of this approach are needed.

Administration, Intranasal↗
PubMed1998

Sequential expression of an amelin gene in mesenchymal and epithelial cells during odontogenesis in rats.

Novel mRNA isoforms encoding the enamel matrix proteins amelin-1, amelin-2 and ameloblastin have been recently described. We have applied detailed immunohistochemical as well as non-radioactive in situ hybridization analyses to follow amelin-1 expression in developing rat incisors and molars. We constructed an expression vector, overproduced recombinant amelin in Escherichia coli and prepared an antibody. In addition to the previously reported amelin mRNA expression patterns in ameloblasts, the amelin message was also detected in pulpal mesenchymal cells including preodontoblasts and young odontoblasts. The signal in these cells persisted until deposition of mantle dentin became evident. The immunolocalization of amelin-1 in preodontoblasts and ameloblasts essentially followed the pattern of mRNA expression. The most intense staining was found in the enamel matrix adjacent to secretory ameloblasts. Focal accumulations of immunoreactive material were found at the dentinoenamel junction during the maturation stage. Also, using 5'-RACE (Rapid Amplification of cDNA Ends) we could confirm only amelin-1 and ameloblastin messages in the total RNA pool from rat molars and conclude that amelin-2 is a truncated form of ameloblastin. The sequential expression of amelin in mesenchymal and epithelial cells suggests it plays a role in cell differentiation during early tooth development.

Ameloblasts↗
PubMed1998

Factors predictive of bile duct stones in patients with acute calculous cholecystitis.

The objective of the study was to investigate the accuracy of using preoperative data for the prediction of bile duct calculi in patients operated on for acute cholecystitis. 279 consecutive patients underwent cholecystectomy with peroperative cholangiography for acute calculous cholecystitis in the Department of Surgery, Lund University Hospital, between 1985 and 1991. The correlation between 13 preoperative clinical and laboratory variables, and the incidence of bile duct calculi was studied. Among the 13 variables tested, serum bilirubin concentration and serum gamma-glutamyltransferase activity were independent factors of predictive significance. These two factors were used for constructing an additive prognostic index for the presence of bile duct stones. Thus, three groups of patients could be identified having a 3, 7-9 or 59% risk of harboring bile duct stones, corresponding to a sensitivity of 61% and a specificity of 93% in predicting the presence of bile duct stones in the 'high-risk' group. Logistic regression analysis permits accurate preoperative identification of bile duct stones in patients with acute calculous cholecystitis.

Acute Disease↗
PubMed1998

Comparative immunochemical analyses of the developmental expression and distribution of ameloblastin and amelogenin in rat incisors.

Mineralized tissues are unique in using proteins to attract and organize calcium and phosphate ions into a structured mineral phase. A precise knowledge of the expression and extracellular distribution of matrix proteins is therefore very important in understanding their function. The purpose of this investigation was to obtain comparative information on the expression, intracellular and extracellular distribution, and dynamics of proteins representative of the two main classes of enamel matrix proteins. Amelogenins were visualized using an antibody and an mRNA probe prepared against the major alternatively spliced isoform in rodents, and nonamelogenins by antibodies and mRNA probes specific to one enamel protein referred to by three names: ameloblastin, amelin, and sheathlin. Qualitative and quantitative immunocytochemistry, in combination with immunoblotting and in situ hybridization, indicated a correlation between mRNA signal and sites of protein secretion for amelogenin, but not for ameloblastin, during the early presecretory and mid- to late maturation stages, during which mRNA signals were detected but no proteins appeared to be secreted. Extracellular amelogenin immunoreactivity was generally weak near secretory surfaces, increasing over a distance of about 1.25 microm to reach a level slightly above an amount expected if the protein were being deposited evenly across the enamel layer. Immunolabeling for ameloblastin showed an inverse pattern, with relatively more gold particles near secretory surfaces and much fewer deeper into the enamel layer. Administration of brefeldin A and cycloheximide to stop protein secretion revealed that the immunoblotting pattern of amelogenin was relatively stable, whereas ameloblastin broke down rapidly into lower molecular weight fragments. The distance from the cell surface at which immunolabeling for amelogenin stabilized generally corresponded to the point at which that for ameloblastin started to show a net reduction. These data suggest a correlation between the distribution of amelogenin and ameloblastin and that intact ameloblastin has a transient role in promoting/stabilizing crystal elongation. (J Histochem Cytochem 46:911-934, 1998)

Amelogenin↗
PubMed1997

Allotype-associated variation in the human gamma3 switch region as a basis for differences in IgG3 production.

High and low serum concentrations of IgG3 are associated with the human G3 m(b) and G3 m(g) allotypes, respectively. We previously hypothesized that a low frequency of switching is the most likely defect in (g) allotype-positive individuals, and therefore analyzed the structure, recombination breakpoints, and binding of nuclear proteins to the switch (S)gamma3 regions of these two allotypes. There are no allotype-associated differences in the length and basic structure of the Sgamma3, since both contain eighteen 79-bp repeats. However, we found a number of allotype-associated nucleotide changes. As in the mouse system, there is a preferential switching to the B site, or switch nuclear protein/nuclear factor-kappaB motif, with a clustering of switch breakpoints at the most 5' residue of the B site. The B site sequence used most frequently in switching was found to be mutated at this nucleotide in the (g) allotype-associated Sgamma3. This change was shown by electrophoretic mobility shift assay to alter the binding of the switch nuclear protein/nuclear factor-kappaB protein to the B site. Taken together, these data suggest that polymorphism within Sgamma3 may contribute to allotype-associated differences in IgG3 switching, and that specific sequences within the Sgamma3 79-bp repeats could be mechanistically important for switch recombination.

Animals↗
PubMed1997

Preventive effect of IgG from EBV-seropositive donors on the development of human lympho-proliferative disease in SCID mice.

The effect of weekly treatments with various gammaglobulin preparations on the development of human B-cell tumors was studied in severe combined immunodeficient (SCID) mice. SCID mice were injected i.p. with human peripheral blood mononuclear cells (PBMCs) from an Epstein-Barr virus (EBV)-seropositive healthy blood donor. Repopulated SCID mice were divided into 7 treatment groups receiving either PBS, 2 commercial gammaglobulin preparations, purified IgG prepared from pooled plasma from EBV-seronegative or -seropositive blood donors, a rabbit anti-serum against EBV envelope glycoprotein gp340 or interferon (IFN)-alpha. All treatments started 1 day after injection of PBMC and continued for 8 weeks. In the PBS-treated control group, 85% of mice developed tumors in the abdominal cavity, mostly with liver metastasis within 150 days. Tumor formation was prevented by treatment with the 2 commercial gammaglobulin preparations as well as by purified IgG from EBV-seropositive donors. In contrast, purified IgG from EBV-seronegative donors, rabbit anti-gp340 anti-serum or IFN-alpha had no effect. Our results indicate that the effect of gammaglobulin is due to the presence of specific antibodies against EBV antigens. Further experiments showed that both the time of onset and the duration of treatment, as well as the dose of Ig, are important factors for prevention of tumor formation. Studies aiming at identification of target antigens for antibodies which prevent lymphoma development may be clinically relevant for prevention and possibly treatment of lympho-proliferative disease in severely immuno-compromised patients.

Abdominal Neoplasms↗
PubMed1997

Mutation pattern in the Bruton's tyrosine kinase gene in 26 unrelated patients with X-linked agammaglobulinemia.

Mutation pattern was characterized in the Bruton's tyrosine kinase gene (BTK) in 26 patients with X-linked agammaglobulinemia, the first described immunoglobulin deficiency, and was related to BTK expression. A total of 24 different mutations were identified. Most BTK mutations were found to result in premature termination of the translation product. Mutations were detected in most BTK exons with a predominance of frameshift and nonsense mutations in the 5' end of the gene and missense mutations in its 3' part, corresponding to the catalytic domain of the enzyme. Nonsense and frameshift mutations were associated with diminished levels of BTK mRNA expression, except for a frameshift mutation in exon 17 and two nonsense mutations in exon 2, indicating that these cases are not confined to penultimate exons. One amino acid substitution (R28H) was found in the pleckstrin homology domain's residue, which is mutated in mice bearing the X-linked immunodeficiency phenotype; another substitution (R307G) was identified in the src homology domain 2. All remaining amino acid substitutions were found in the catalytic domain of Btk.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1997

The role of enamel matrix proteins in the development of cementum and periodontal tissues.

The role of Hertwig's epithelial root sheath (HERS) and of the enamel-related proteins in the development of acellular cementum are reviewed. The inner layer of HERS is an apical extension of the ameloblastic layer in the crown. A number of studies now indicate that the cells of HERS have a secretory stage similar to the ameloblasts. In rats and mice the secretory product of the HERS cells does not seem to be amelogenin, which is the main protein of the enamel matrix. In humans, however, amelogenin has been demonstrated at the apical ends of the roots of developing teeth. The development and distribution of coronal cementum in various species are discussed. The amelogenins have been remarkably well conserved between species. Experiments in monkeys have shown that it is possible to induce formation of acellular cementum by application of porcine enamel matrix on a denuded root surface, which thereby promotes periodontal regeneration. These results further support the idea that enamel-related proteins are involved in cementum formation.

Alveolar Process↗
PubMed1997

Structural analysis of human gamma 3 intervening regions and switch regions: implication for the low frequency of switching in IgG3-deficient patients.

High and low serum concentrations of IgG3 are associated with the human G3m(b) and G3m(g) allotypes, respectively. In the present study, we analyzed the structure of the S gamma 3 and I gamma 3, the switch frequency, switch breakpoints and the levels and initiation sites of I gamma 3 transcripts both in normal blood donors expressing (b) or (g) allotypes as well as IgG3-deficient (D) patients. A low switch frequency to gamma 3 was found in the (g) allotype IgG3D patients which may be caused in part by the allotype-associated mutations in the S gamma 3 region and in part by additional individual mutations observed in the A (SNAP) and B (SNIP/ NF-kappa B) sites in the S gamma 3 repeat region. A higher I gamma 3 germ-line (GL) transcriptional rate was seen in cells from the IgG3D patient, suggesting that low levels of GL I gamma 3 transcripts are not a major contributing factor to the defect. However, individual mutations in the I gamma 3 region and differential splicing of GL I gamma 3 transcripts were found which may affect the switching process.

Base Sequence↗
PubMed1997

Polymorphism of the IGHG3 gene in cattle.

We cloned and analyzed the gene (IGHG3) encoding cattle IgG3 using a spleen cDNA library and a genomic phage clone. IGHG3 differs most remarkably from IGHG1 and IGHG2 in the structure of its hinge. The IGHG3 hinge is encoded by two exons, one of which encodes a 22 amino acid 3' extension of the CH1 exon. The IGHG3 gene is highly homologous to the C-gamma pseudogene previously reported. Seventy-one DNA samples from different cattle were tested by pulsed-field gel electrophoresis and Southern blot to detect genetic polymorphisms. This analysis revealed two different alleles which we designated IGHG3(a) and IGHG3(b). The two putative alleles differ from each other by a 6 amino acid substitution in the coding region and an 84 base pair insertion in the intron between the CH2 and CH3 exons. Our data also indicate that the cattle heavy chain locus spans approximately 400 kilobases from IGHM to IGHA and encodes only three IgG subclasses, all of which are transcriptionally active.

Alleles↗
PubMed1997

Clustering of missense mutations in the ataxia-telangiectasia gene in a sporadic T-cell leukaemia.

Ataxia-telangiectasia (A-T) is a recessive multi-system disorder caused by mutations in the ATM gene at 11q22-q23 (ref. 3). The risk of cancer, especially lymphoid neoplasias, is substantially elevated in A-T patients and has long been associated with chromosomal instability. By analysing tumour DNA from patients with sporadic T-cell prolymphocytic leukaemia (T-PLL), a rare clonal malignancy with similarities to a mature T-cell leukaemia seen in A-T, we demonstrate a high frequency of ATM mutations in T-PLL. In marked contrast to the ATM mutation pattern in A-T, the most frequent nucleotide changes in this leukaemia were missense mutations. These clustered in the region corresponding to the kinase domain, which is highly conserved in ATM-related proteins in mouse, yeast and Drosophila. The resulting amino-acid substitutions are predicted to interfere with ATP binding or substrate recognition. Two of seventeen mutated T-PLL samples had a previously reported A-T allele. In contrast, no mutations were detected in the p53 gene, suggesting that this tumour suppressor is not frequently altered in this leukaemia. Occasional missense mutations in ATM were also found in tumour DNA from patients with B-cell non-Hodgkin's lymphomas (B-NHL) and a B-NHL cell line. The evidence of a significant proportion of loss-of-function mutations and a complete absence of the normal copy of ATM in the majority of mutated tumours establishes somatic inactivation of this gene in the pathogenesis of sporadic T-PLL and suggests that ATM acts as a tumour suppressor. As constitutional DNA was not available, a putative hereditary predisposition to T-PLL will require further investigation.

Amino Acid Sequence↗
PubMed1997

Oral administration of antibodies as prophylaxis and therapy in Campylobacter jejuni-infected chickens.

Passive immunity against gastrointestinal infections has recently been successfully applied as prophylaxis and therapy in patients in a variety of virally and bacterially induced infections. Campylobacter jejuni is frequently associated with acute diarrhoea in humans, and several species of animals have been shown to transmit the disease, although birds have been implicated as the main source of infection. We used bovine and chicken immunoglobulin preparations from the milk and eggs, respectively, of immunized animals for prophylactic and therapeutic treatment of chickens infected with C. jejuni. A marked prophylactic effect (a >99% decrease in the number of bacteria) was noted using either antibody preparation, whereas the therapeutic efficacy, i.e. when antibodies were given after the infection was established, was distinctly lower (80-95%) as judged by faecal bacterial counts. These observations may serve as a starting point for experiments aimed at elimination of the infection in an industrial or farm setting. It may also encourage future attempts to treat, prophylactically or therapeutically, patients with Campylobacter-induced diarrhoea.

Administration, Oral↗
PubMed1997

Characterization of the bovine C alpha gene.

The complete genomic sequence of a bovine C alpha gene is reported here. The genomic sequence was obtained from a C alpha phage clone that had been cloned from a genomic EMBL4 phage vector library. The C alpha sequence had previously been expressed as a chimeric antibody and identified as IgA using IgA-specific antibodies. Intron/exon boundaries were determined by comparison of the genomic sequence with an expressed bovine C alpha sequence obtained from spleen by reverse transcription-polymerase chain reaction (RT-PCR). Analysis of 50 Swedish bovine genomic DNA samples using genomic blots and five different restriction enzymes failed to detect evidence of polymorphism. However, PstI digests of Brown Swiss DNA showed a restriction fragment length polymorphism (RFLP), suggesting that at least two allelic variants of bovine IgA exist. Comparison of the deduced amino acid sequence of bovine IgA with sequences available for other species indicated that the highest homology was with that of swine, another artiodactyl. This was the highest homology observed for all mammalian IgA compared except for that between IgA1 and IgA2 in humans. Bovine IgA shares with rabbit IgA3 and IgA4, an additional N-linked glycosylation site at position 282. However, the collective data indicate that cattle are like swine and rodents and unlike rabbits in having a single locus of the gene encoding IgA of this species.

Amino Acid Sequence↗
PubMed1997

Characterization of the bovine epsilon gene.

Immunoglobulin E is quantitatively a minor immunoglobulin class in serum, but nevertheless the major class of antibody mediating type I hypersensitivity reactions and hence, type I allergic phenomena. The bovine epsilon gene is one of the as yet uncharacterized mammalian immunoglobulin genes. We have therefore cloned and determined the cDNA sequence and genomic organization of the gene. It contains four constant region domain-encoding exons (CH1 to CH4) with a high homology to sheep C epsilon (87%) and to a lower degree to dog (62%), horse (58%), chimpanzee, orangutan, human (55%), mouse (52%) and rat (52%) C epsilon genes. Southern blot analysis of bovine genomic DNA, revealed the existence of a single C epsilon gene with a presence of allelic restriction fragment length polymorphism (RFLP).

Amino Acid Sequence↗