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Biomedical subjects

L Hammarström

Publications and source records attributed to L Hammarström.

At least 91 records · Page 5Linked to original sources
PubMed1997

At least three hepatitis C virus strains implicated in Swedish and Danish patients with intravenous immunoglobulin-associated hepatitis C.

BACKGROUND: Three reported Swedish cases of hepatitis C in patients receiving an intravenous immunoglobulin (Gammagard, Baxter Healthcare, Deerfield, IL) were among the first to bring to light a worldwide outbreak of hepatitis C associated with non-solvent/detergent (SD)-treated Gammagard. In February 1994, all implicated batches of Gammagard were recalled and exposed patients traced. STUDY DESIGN AND METHODS: Sera from all identified and hepatitis C-viremic Swedish and Danish patients (n = 14) exposed to the implicated batches underwent hepatitis C virus genotyping and sequencing of the core region and hypervariable region 1 of E2. Genomic amplification was also done on 15 non-SD-treated batches of Gammagard. RESULTS: Twelve patients were infected with subtype 1a and surprisingly, two with subtype 2b. Analysis of the core region showed identical sequences in four patients and the only consistently positive batch. Five patients shared another sequence, whereas three other subtype 1a patients each manifested unique sequences. The two subtype 2b isolates were identical. Genomic fingerprinting of the hypervariable region confirmed identity within each group with great stringency. Amplification with isolate-specific primers showed mixed infection in one patient whose exposure was confined to a single batch. CONCLUSION: The few batches implicated presumably were contaminated with several strains.

Adolescent↗
PubMed1997

Enamel matrix, cementum development and regeneration.

Studies during the last 20 years have indicated that enamel-related proteins are involved in the formation of cementum. In the present article, this relation is further explored. Attention is called to the fact that coronal acellular extrinsic fiber cementum is formed on the enamel surface in a number of species. The composition of the enamel matrix proteins and the expression of these proteins during root formation are briefly reviewed. The dominating constituent of the enamel matrix, amelogenin, is shown by means of immunohistochemistry to be expressed in human teeth during root formation. Amelogenin was also found to be present in Tomes' granular layer of human teeth. When mesenchymal cells of the dental follicle were exposed to the enamel matrix a non-cellular hard tissue matrix was formed at the enamel surface. Application of porcine enamel matrix in experimental cavities in the roots of incisors of monkeys induced formation of acellular cementum that was well attached to the dentin. In control cavities without enamel matrix, a cellular, poorly attached hard tissue was formed. The present studies provide additional support to the idea that enamel matrix proteins are involved in the formation of acellular cementum and also that they have the potential to induce regeneration of the same type of cementum.

Amelogenin↗
PubMed1997

Periodontal regeneration in a buccal dehiscence model in monkeys after application of enamel matrix proteins.

There is increasing evidence that cells of the epithelial root sheath synthesize enamel matrix proteins and that these proteins play a fundamental role in the formation of acellular cementum, the key tissue in the development of a functional periodontium. The purpose of the present study was to explore the effect of locally applied enamel matrix and different protein fractions of the matrix on periodontal regeneration in a buccal dehiscence model in monkeys. Buccal, mucoperiosteal flaps were raised from the canine to the 1st molar on each side of the maxilla. The buccal alveolar bone plate, the exposed periodontal ligament and cementum were removed. Various preparations of porcine enamel matrix with or without vehicles were applied before the flaps were repositioned and sutured. After 8 weeks, the healing was evaluated in the light microscope, and morphometric comparisons were made. Application of homogenized enamel matrix or an acidic extract of the matrix containing the hydrophobic, low molecular weight proteins, amelogenins, resulted in an almost complete regeneration of acellular cementum, firmly attached to the dentin and with collagenous fibers extending over to newly formed alveolar bone. After application of fractions obtained by neutral EDTA extraction containing the acidic, high molecular weight proteins of the enamel matrix, very little new cementum was formed and hardly any new bone. The results of the controls in which no test substance was applied before the repositioning of the flap, were very similar to those obtained with the EDTA extracted material. Propylene glycol alginate (PGA), hydroxyethyl cellulose and dextran were tried as vehicles for the enamel matrix preparations. Only PGA in combination with the amelogenin fraction resulted in significant regeneration of the periodontal tissues.

Alginates↗
PubMed1997

Formulation of enamel matrix derivative for surface coating. Kinetics and cell colonization.

Enamel Matrix Derivative (EMD) contains a protein complex belonging to the amelogenin family. Enamel matrix as well as EMD have been found to promote periodontal regeneration when applied onto denuded root surfaces in dehiscence models. In the present studies it is shown that propylene glycol alginate (PGA) is a suitable vehicle for EMD for its local application. EMD can be dissolved in PGA at an acidic pH, resulting in a highly viscous solution. At neutral pH and body temperature the viscosity decreases and EMD precipitates. Multilayers of EMD on mineral or protein surfaces have been analysed using ellipsometry, total internal reflection fluorescence (TIRF) and biospecific interaction analysis (BIA). The studies show that EMD adsorbs both to hydroxyapatite and collagen and to denuded dental roots. It forms insoluble spherical complexes, and detectable amounts remain at the site of application on the root surface for two weeks, as shown with radiolabelled protein in rats and pigs. Scanning electron micrograph (SEM) studies on monkey teeth further indicate that EMD in PGA may promote repopulation of fibroblast-like cells during the first weeks after application.

Adsorption↗
PubMed1997

In vitro studies on periodontal ligament cells and enamel matrix derivative.

The recognition that periodontal regeneration can be achieved has resulted in increased efforts focused on understanding the mechanisms and factors required for restoring periodontal tissues so that clinical outcomes of such therapies are more predictable than those currently being used. In vitro models provide an excellent procedure for providing clues as to the mechanisms that may be required for regeneration of tissues. The investigations here were targeted at determining the ability of enamel matrix derivative (EMD) to influence specific properties of periodontal ligament cells in vitro. Properties of cells examined included migration, attachment, proliferation, biosynthetic activity and mineral nodule formation. Immunoassays were done to determine whether or not EMD retained known polypeptide factors. Results demonstrated that EMD under in vitro conditions formed protein aggregates, thereby providing a unique environment for cell-matrix interaction. Under these conditions, EMD: (a) enhanced proliferation of PDL cells, but not of epithelial cells; (b) increased total protein production by PDL cells; (c) promoted mineral nodule formation of PDL cells, as assayed by von Kossa staining; (d) had no significant effect on migration or attachment and spreading of cells within the limits of the assay systems used here. Next, EMD was screened for possible presence of specific molecules including: GM-CSF, calbindin D, EGF, fibronectin, bFGF, gamma-interferon, IL-1 beta, 2, 3, 6; IGF-1,2; NGF, PDGF, TNF, TGF beta. With immunoassays used, none of these molecules were identified in EMD. These in vitro studies support the concept that EMD can act as a positive matrix for cells at a regenerative site.

Calbindins↗
PubMed1996

ATM mutations in cancer families.

Ataxia-telangiectasia (A-T) is a multisystem recessive disease characterized clinically by cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, sensitivity to radiomimetic agents, and cancer predisposition. This pleiotropic disorder is caused by mutations in the ATM (mutated in A-T) gene, which is located in the human chromosomal region 11q22-q23. The ATM gene product is a member of a novel family of large proteins implicated in the regulation of the cell cycle and response to DNA damage. Heterozygosity for A-T was previously suggested to be associated with an increased risk of tumors, particularly female breast cancer. Because of loss of constitutional heterozygosity at 11q22-q23 is a frequent event in breast and other tumors, suggesting the presence of a tumor suppressor gene(s) in this region, we screened blood DNA samples from 88 unrelated breast cancer patients of Swedish cancer families for ATM mutations using single-strand conformation polymorphism analysis. All patients had a family history of tumors previously associated with A-T heterozygosity or homozygosity. We demonstrate the first three germ-line mutations in ATM identified by screening of breast cancer patients. Two mutations were previously found in A-T homozygotes and one mutation was a 1-bp insertion. All mutations were found in families with a large number of tumors, however, they did not cosegregate with malignancies. Although the proportion of A-T carriers in this sample seems to be higher than expected by chance, larger studies and pooled data sets will be required to establish that an A-T allele confers cancer susceptibility in heterozygotes.

Adenine↗
PubMed1996

The ATM gene and susceptibility to breast cancer: analysis of 38 breast tumors reveals no evidence for mutation.

Heterozygosity for ataxia-telangiectasia (A-T), a cancer-prone recessive syndrome, has been associated with an increased risk of breast cancer. The gene for A-T (ATM) is located at chromosomal region 11q22-q23, a region of frequent loss of constitutional heterozygosity in breast and other tumors. Loss of constitutional heterozygosity at 1lq22-q23 was found in 47% of informative cases in the series of primary tumors analyzed in this study. To investigate the role of ATM in breast cancer, we have determined the complete genomic organization of the gene, developed an exon-scanning PCR single-strand conformation polymorphism (PCR-SSCP) assay for mutation detection of ATM, and screened 38 consecutive breast tumors for mutations using both genomic DNA- and cDNA-based assays. In addition to common ATM polymorphisms detected both in the coding sequence and in flanking introns, seven unique SSCP alleles were identified in six tumor DNAs. Sequence analysis of these alleles revealed rive nucleotide substitutions that were predicted to change the encoded amino acid. However, PCR-SSCP and nucleotide sequencing analysis of the paired blood samples and of an extended sample size of a total of 224 chromosomes indicated that these SSCP patterns represent constitutional rare polymorphisms with a frequency between 0.005 and 0.023. Because the majority of A-T mutations are null mutations and none of the ATM alleles found in breast cancer samples would lead to the truncation of the translation product, we conclude that, in this initial sample of sporadic breast cancer patients, there was no evidence for an increased number of A-T carriers. In addition, because no somatic mutations were found, our study rules out the ATM gene as the frequently altered tumor suppressor gene at 11q23.

Ataxia Telangiectasia↗
PubMed1996

Expression of amelogenin mRNA sequences during development of rat molars.

The expression of amelogenin mRNA in growing rat molars was studied. Northern blotting and the analysis of cDNA isolates revealed two predoninant variants. One group of cDNA inserts contained sequences of a long mRNA version and the other group contained mRNA sequences of the shorter leucin-rich amelogenin polypeptide (LRAP). The LRAP group was deficient in an internal stretch which coded for a peptide with a high potential for beta turns. Northern blot experiments showed that most amelogenin RNA in rat teeth was represented by two bands of 1.1 and 0.8 kb. Two oligonucleotide probes were designed that were specific for the long version and for the LRAP variant. The probes were used for in situ hybridization experiments on sections of developing maxillar teeth of rats between day 2 and day 15 after birth. Both RNA species were accumulated concomitantly and exclusively in cells of the inner enamel epithelium. Expression was first observed at the mesial cusp sides and finally involved the whole ameloblast layer except for the cells adjacent to the enamel-free region at the tip of the cusps. The early amelogenin RNA expression occurred adjacent to the initial deposition of the dentin matrix. Low amounts of amelogenin RNA persisted after the differentiation of ameloblasts into the maturative stage. The sequence of events was similar in all three molars.

Amelogenin↗
PubMed1996

A novel gene expressed in rat ameloblasts codes for proteins with cell binding domains.

Two variants of an mRNA sequence are identified that are expressed at high levels in rat ameloblasts during the formation of the enamel matrix. The sequences contain open reading frames for 407 and 324 amino acid residues, respectively. The encoded proteins, which we call amelins, are rich in proline, glycine, leucine, and alanine residues and contain the peptide domain DGEA, an integrin recognition sequence. The sequences coding for the C-terminal 305 amino acid residues, the 3' nontranslated part, and a microsatellite repeat at the nontranslated 5' region are identical in both mRNA variants. The remaining 5' regions contain 338 nucleotides unique to the long variant, 54 common nucleotides, and 46 nucleotides present only in the short variant. Eleven nucleotides have the potential to code for 5 amino acids of both proteins in different reading frames. The reading frame of the longer variant includes codons for a typical N-terminal signal peptide. The amelins are likely to be constituents of the enamel matrix and the only proteins that have so far been implicated in binding interactions between the ameloblast surface and its extracellular matrix.

Ameloblasts↗
PubMed1996

Amelin: an enamel-related protein, transcribed in the cells of epithelial root sheath.

Since 1974, when Slavkin and his collaborators proposed the epithelial origin of cementum, many experiments have been carried out to provide evidence for deposition of enamel-related proteins along the root surface. However, neither amelogenin nor other proteins have fully satisfied expectations. In previous studies, we have identified a novel mRNA coding for an extracellular-like protein which we called amelin. It was expressed at high levels in secretory and postsecretory ameloblasts in rat molars and incisors. In situ hybridization experiments described in the present study also localized the amelin message to epithelial cells adjacent to the peripheral surface of newly deposited dentin in the root end and to cells embedded in cellular cementum in molars. In incisors, the amelin RNA positive cells were detected in the area where cementum formation had been initiated. No amelogenin RNA signal was found in the cells at the root surface. We postulate that the epithelial cells of the root sheath as well as the ameloblasts are synthesizing amelin which might be one of the key proteins coupled to the process of cementogenesis.

Ameloblasts↗
PubMed1996

Duplications and deletions of the human IGHC locus: evolutionary implications.

A limited number of deletions and duplications within the human immunoglobulin heavy chain constant locus (IGHC) has previously been reported. We studied the IGHC locus in about 500 individuals representing three major races of human, Negroid (Gambian), Mongoloid (Japanese and Chinese), and Caucasoid (Iranian and Swedish). The haplotype frequency of duplications is highest in the Mongoloid population (22%), followed by the Caucasian (10%) and Negroid (5%) populations. The corresponding frequency of deletions are 2, 1.5, and 3.5%, respectively. New types of multiple duplications were found in this study on different genetic (H haplotype and racial) backgrounds. The most common duplication, found in all populations studied, encompasses the IGHA1-IGHE genes. The only deletion common to all racial groups is an isolated deletion of the IGHG4 gene. Our data are consistent with the hypothesis that the Caucasoid-Mongoloid group diverged from the hominoid ancestor after development of the Negroid populations, with subsequent evolution within the respective groups thereafter.

Electrophoresis, Gel, Pulsed-Field↗
PubMed1996

Helicobacter pylori infections in IgA deficiency: lack of role for the secretory immune system.

During the last years considerable attention has been focused on the possibility of the development of an oral vaccine against Helicobacter pylori. However, Helicobacter infection is known to be life-long, despite a vigorous immune response, and the hypothesis that an increased local production of secretory IgA in the gastric mucosa, due to vaccination, should protect against the colonization of the bacterium may therefore be questioned. In this study, when comparing the seropositivity and titre against H. pylori in IgA-deficient patients and age-related normal blood donors, it appears that lack of secretory IgA does not seem to have any major influence on the prevalence of the infection, nor is it reflected in titres of specific IgG antibodies. These results many argue against a pivotal role for IgA in the defence against Helicobacter, and raise questions about current strategies for the development of an oral vaccine against H. pylori and may point to a need for alternative therapeutic strategies.

Adult↗
PubMed1996

Reduction in serum levels of antimitochondrial (M2) antibodies following immunoglobulin therapy in severe combined immunodeficient (SCID) mice reconstituted with lymphocytes from patients with primary biliary cirrhosis (PBC).

The effect of gammaglobulin treatment on autoantibody production was investigated in SCID mice reconstituted with human peripheral blood mononuclear cells (PBMC) obtained from patients with PBC. All reconstituted mice displayed the presence of human antimitochondrial antibodies (alpha M2Ab) of both IgG and IgM types before treatment with human immunoglobulin. Two weeks after i.p. injection of 20 x 10(6) PBMC into SCID mice, i.p. treatment with various preparations of human immunoglobulin was initiated. In control animals treated with saline, serum levels of human alpha M2Ab of the IgG type increased with time, peaking around 4 weeks after reconstitution. In contrast, human IgG autoantibodies rapidly decreased in all animals treated with human IgG. Treatment with a human IgM preparation had no effect on serum levels of alpha M2Ab of the IgG type. The results may suggest that the pronounced reduction of specific IgG autoantibodies was due to an increased catabolism of human IgG, including the autoantibodies, in the gammaglobulin-treated mice. Although the production of human alpha M2Ab in reconstituted mice could be easily shown, PBC-specific liver lesions or bile duct destruction were not observed, irrespective of treatment protocol.

Animals↗
PubMed1996

The localization of epithelial root sheath cells during cementum formation in rat molars.

The purpose of this study was to investigate the distribution of epithelial cells and the fate of the basement membrane along the root surface of rat molars during cementogenesis, and to test the hypothesis that the Hertwig's epithelial root sheath (HERS) cells remain on the root surface if mineralization is inhibited. To demonstrate the HERS cells and basement membrane, immunohistochemistry with antibodies against keratin and laminin were used. The dentin matrix mineralization was inhibited by a single injection of 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP). A modified Gomori staining method was used to monitor the inhibition of mineral formation in dentin and cementum. Paraffin sections were stained with haematoxylin-eosin, and freeze-dried sections were used for Gomori and immunohistochemical stainings. We found that the formation of acellular cementum was suppressed above the dentin with inhibited mineralization. Instead, a hyperplastic matrix, different from acellular cementum, covered the dentin. This hyperplastic cementum had keratin- and laminin-positive cells incorporated; such cells were never incorporated in normal acellular cementum. The later formation of cellular cementum correlated, in controls, with the disappearance of HERS cells from the root surface. Treatment with HEBP resulted in a persistent presence of epithelial cells, interpreted as an inhibition of their disappearance. In conclusion, there is evidence that the cells of HERS are involved in the development of both acellular and cellular cementum. The developmental processes of these tissues appear in some way to be influenced by or associated with the initial mineralization of the dentin.

Animals↗
PubMed1996

Origins of cementum.

There are diverging opinions about the role of Hertwig's epithelial root sheath in the formation of cementum. In the present review this role is discussed. There is increasing evidence that Hertwig's epithelial root sheath is actively involved in the formation of both acellular and cellular cementum. The development of acellular cementum seems to be associated with secretion of enamel-related proteins by cells of the epithelial root sheath. Formation of the matrix for cellular cementum appears to be induced by exposure of the inner layer of the epithelial root sheath to the mesenchymal cells in the dental follicle. Experimental studies with 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) indicate that the formation of acellular cementum must be preceded by mineralization of the mantle dentin. If the mineralization is inhibited by means of HEBP, there is precocious separation of the two layers of the epithelial root sheath after which matrix for a cellular type of cementum is formed.

Animals↗
PubMed1996

Fatal outcome of disseminated Mycobacterium avium infection in childhood. A case of primary incompetent monocyte/macrophage function?

Disseminated BCG infection rarely heals, and disseminated disease caused by the Mycobacterium avium complex usually has a poor prognosis with a short time to death. The case of a boy who died after 9 years of diagnosed disseminated M. avium complex infection is described. He showed no signs of previously known immunodeficiency except an incompetent primary monocyte/macrophage function. This case has been commented on in Acta Paediatrica Scandinavia (1982) as "the first infant to survive a generalized BCG infection".

Adolescent↗
PubMed1996

Passive immunity against diarrhoea.

Passive immunity against a variety of respiratory and gastrointestinal pathogens has recently been increasingly used clinically, and oral administration of antibodies of both human and non-human origin has been tried both for prophylaxis and treatment of infections. Although the former type of therapy has been shown to be effective, data on the latter are still scarce. This commentary focuses on recent studies on successful oral therapeutic administration of bovine immunoglobulins.

Animals↗