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Biomedical subjects

L Hammarström

Publications and source records attributed to L Hammarström.

At least 217 records · Page 12Linked to original sources

Effect of a high dose of fluoride on resorbing osteoclasts in vivo.

Histomorphometric analysis of osteoclasts resorbing bone above the erupting first rat molar tooth germ was made at 1, 2, 6, 24, and 48 h following systemic administration of a single high dose of sodium fluoride. Compared to the number of osteoclasts in control rats, a significant reduction was observed in the number of actively resorbing osteoclasts in fluoride-injected rats at 2 and 6 h after dose administration, after which a gradual increase to control levels was observed. A locally increased number of inactive osteoclasts, not attached to bone surfaces, accompanied the reduced number of active osteoclasts.

Animals↗

Effects of phosphonoformic and phosphonoacetic acids on developing enamel of rat molars.

The effect of a single subcutaneous injection of different dosages of phosphonoformic or phosphonoacetic acid on the developing dental tissues of the rat molar was studied. The substances were injected at different rat ages and effects on the developing teeth were analyzed by means of histochemistry of frozen sections and scanning electron microscopy. Molars of rats injected at the age of 10 or 15 days showed no pathologic changes. Administration of phosphonoacetic acid in a dosage of 10 or 20 mg P/kg b.w. had no demonstrable effect on the dental tissues in any of the animals. Phosphonoformic or phosphonoacetic acid in a dosage of 10 or 30 mg P/kg b.w. respectively induced subameloblastic cysts 24 h after injection to 4-7-day-old rats. The cysts were mainly localized on the mesial sides of the cusps under ameloblasts in the late secretory stage. Calcified depositions were seen in the ameloblastic layer lining the cystic cavities. A thin zone, the staining of which indicated a high mineral content, was seen in the outermost enamel layer under the cysts. A few days later, enamel hypoplasias were seen in areas previously occupied by cysts. A lightly stained line was observed in the enamel matrix demarcating the amount of enamel matrix formed before and after the injection. Hypoplastic lesions were also noted in the enamel surface of newly erupted molars. These findings suggest that the two injected monophosphonates can induce pathologic changes in the developing enamel organ and hypoplasias in the enamel.

Ameloblasts↗

Dynamics of dentoalveolar ankylosis and associated root resorption.

The present experimental studies in monkeys were undertaken to study the initiation and progression of dentoalveolar ankylosis of replanted teeth and associated root resorption. Maxillary and mandibular lateral incisors were extracted and replanted after an extraoral period of 15 min or 1 h. Teeth with an extraoral period of 1 h were endodontically treated. Half the number of monkeys were given antibiotics at the time of replantation. The observation periods varied from 2 days to 40 weeks. Irrespective of the length of the extraoral period, initial root resorption and minor areas of ankylosis were found 1 week after replantation. The initial ankylosis was not preceded by root resorption. In teeth replanted after an extraoral period of 15 min the ankylotic area did not increase with increasing time after replantation. Instead the periodontal membrane was re-established, separating the root surface from the alveolar bone. In teeth replanted after an extraoral period of 1 h, the initial ankylotic area increased with increasing time after replantation. Eight weeks and more after replantation, most of the periodontal membrane was replaced by bone covered by osteoblasts and occasional osteoblasts that were in continuity with the endosteal cells outlining the marrow spaces of the alveolar bone. The cementum and dentin were then gradually resorbed with increasing time after replantation. Antibiotics given at the time of replantation reduced the initial inflammation in the periodontal membrane and the inflammatory root resorption after all observation periods and it also seemed to some extent to prevent bacteria from entering the necrotic pulp tissue. Based on the present results it is suggested that root resorption associated with dentoalveolar ankylosis is initiated by endosteal osteoblasts and is thus a hormonally regulated process. This is in contrast to inflammatory root resorption, which seems to be triggered by inflammatory cells.

Animals↗

Autoantibody formation after bone marrow transplantation. Comparison between acetylcholine receptor antibodies and other autoantibodies and analysis of HLA and Gm markers.

Clinical myasthenia gravis has been reported in an increased frequency after bone marrow grafting. The number of bone marrow transplanted patients making IgG autoantibodies directed against the autoantigens cardiolipin, SS-B (La) and thyroglobulin was found to be significantly lower as compared to the autoantigen acetylcholine receptor protein. The occurrence of antibodies to single-stranded DNA was found in a lower frequency than acetylcholine receptor antibodies but the difference was not statistically significant. Antibodies to cardiolipin were frequently observed prior to grafting. The G1m1,2 and G3m5 phenotype frequency did not differ in individuals who developed receptor antibodies from that found in the normal population. Analysis of HLA antigens in this patient group revealed no association to HLA B8/DR3 or B35/DR1. This may indicate that the etiology of myasthenia gravis induced by bone marrow grafting differs as compared with the spontaneous form of myasthenia gravis and the penicillamine-induced disease.

Antibody Formation↗

Developmental disturbances of the rat molar induced by two diphosphonates.

Very few reports have been published about the effects of diphosphonates on the cells and tissues of developing teeth. The present study was designed to investigate possible morphological changes in ameloblasts and odontoblasts and relate these changes to defects in the enamel surface of erupted teeth. Young rats were injected subcutaneously with single or multiple doses of HEDP or Cl2MDP (10 mg P/kg b.w.). Light microscopic examination of developing maxillary first molars showed that single injections of HEDP or Cl2MDP induced subameloblastic cysts between the secretory ameloblasts and the developing enamel. The ameloblastic lining of the cysts contained numerous calcified deposits. A few days after injection, hypoplasias were seen in the enamel in areas previously occupied by cysts. In the erupted teeth, scanning electron microscopic examination revealed enamel hypoplasias which were mainly localized on the mesial sides of the cusps. In addition to the previously mentioned disturbances, multiple injections resulted in more extensive cysts, some of which contained non-mineralized enamel matrix. Inhibition of the mineralization of dentin and alveolar bone was also noticed.

Ameloblasts↗

Restriction fragment length polymorphism analysis of T-cell receptor genes in inflammatory bowel disease.

The etiology of inflammatory bowel disease is still unknown, but autoimmune phenomena are thought to play an important role. However, only a weak association between HLA or immunoglobulin allotypes and inflammatory bowel diseases has been noted. Recently, DNA markers (restriction fragment length polymorphism (RFLP) pattern) of T-cell receptor gene allotypes have been reported and shown to be linked to susceptibility to autoimmune disease. We investigated the T-cell receptor RFLP pattern in inflammatory bowel diseases. No linkage to the constant region alpha- and beta-chain markers was observed, and no differences in the frequencies of 'genoallotypes' was found between patients and normal blood donors.

Colitis, Ulcerative↗

No influence of conversions affecting allotype expression on the IgG subclass restriction of specific antibodies.

Antibodies against any given antigen are usually restricted to a particular class or subclass, a finding which has been suggested to be due to a preferential association between particular VH and CH genes. The DNA sequences regulating this process are as yet entirely unknown. It is likely however that some of these regulatory sequences are located within or in the immediate vicinity of the immunoglobulin genes themselves. We therefore analyzed the IgG subclass pattern of specific antibodies in sera from individuals displaying mutations, duplications, deletions or gene conversions event (replacing parts of the constant region genes of one subclass with that of another) affecting the allotype expression of immunoglobulin heavy chain constant region genes. Marked influences on antibody levels were noted in sera from individuals displaying duplication or deletions of constant region genes. However, in no case of gene conversion or mutation was there any measurable influence on the antibody pattern, clearly suggesting a lack of VH gene regulation by sequences within and possibly also immediately downstream of the constant region genes.

Antibody Specificity↗

Clonal immunoglobulin gene rearrangements in primary mediastinal clear cell lymphomas.

Cells from two patients with primary mediastinal tumors of clear cell type were characterized by immunological and molecular biological techniques. In both cases a B cell immunophenotype was suggested by the positive staining for the B1 (CD20), B4 (CD19), Leu 14 (CD22), as well as staining with other B monoclonal antibodies by immunohistochemistry. However, no definitive evidence for the expression of Ig light or heavy chains at the protein level was found. Southern blot analysis of Ig heavy and light chain gene rearrangements revealed clonal B cell populations in both cases. There was no indication of a somatic joining of T cell receptor (TCR) genes using probes for TCR beta and or TCR gamma genes. Thus, our results suggest a clonal B cell origin of clear cell lymphomas in the mediastinum.

Antigens, Differentiation↗

An enzyme-linked immunosorbent assay for the determination of the IgA subclass distribution of antigen-specific antibodies.

An ELISA for the determination of the IgA subclass distribution of antigen-specific antibodies was developed using commercially available monoclonal anti-IgA1 anti-IgA2 subclass antibodies. Furthermore an anti-A2m allotype-specific antibody was included in the study. The specificity and sensitivity of the monoclonal anti-immunoglobulin antibodies used was analyzed using sera from normal and IgA class- or subclass-deficient individuals (with or without homozygous C alpha 1 subclass gene deletions). Human IgA1 and IgA2 hybridoma antibodies were also used. In this particular assay, only two out of four tested anti-IgA1 and two out of three tested anti-IgA2 antibodies proved to be specific for their corresponding IgA subclass. The anti-A2m(2) monoclonal antibody was shown to be specific for the corresponding allotype. These ELISA methods may facilitate further work on the regulation of IgA subclass production in man.

Agammaglobulinemia↗

IgG subclass-associated affinity differences of specific antibodies in humans.

Human IgG subclasses differ in their biologic functions and are restricted as specific antibodies to certain Ag. The basis for this restriction is unknown but in order to characterize it further, we obtained serum preparations containing one single subclass by using subclass-specific mAb in affinity chromatography. Subsequently we determined the affinity of antibodies in the four IgG subclasses for gp30/p25, a hepatitis B surface Ag (HBsAg) complex, for a nine-amino acid cyclical peptide representing residues 139 to 147 of HBsAg, and for a peptide representing residues 126 to 140 of the hepatitis B virus pre-S2 region and the relative avidity of IgG1 and IgG2 antibodies for purified pneumococcal polysaccharide type 3. Affinities to the HBsAg showed a clear pattern of decreasing affinity in the order IgG1 greater than IgG2 greater than IgG3 greater than IgG4 both in sera from vaccinated and from naturally infected individuals. The relative avidities of antibodies to the polysaccharide Ag had a reverse pattern, IgG2 greater than IgG1. In individuals with or without Ig H chain gene deletions where the anti-HBsAg response was restricted to one subclass, the affinity was similar to that observed for the same subclass in sera from individuals who in addition possessed high or low affinity antibodies of other subclasses.

Adult↗

IgG subclass distribution of antiviral antibodies in common variable immunodeficiency: effect of substitution therapy.

Immunoglobulin G subclass titers to three herpesviruses (herpes simplex; HSV; cytomegalovirus, CMV; varicella zoster virus, VZV) were examined in patients with common variable immunodeficiency (CVI) before and after immunoglobulin substitution. Like healthy controls, CVI patients expressed IgG1 and IgG3 to HSV and CMV, but only IgG1 to VZV. Individual titers varied as in healthy individuals, but as a mean, specific IgG titers were lowered in proportion to the decrease of total IgG. HSV and CMV IgG3 titers were relatively higher than the IgG1 titers in CVI patients, resulting in a lower IgG1/IgG3 ratio than in healthy individuals (P = 0.025 and 0.05, respectively). The high IgG3 titers in CVI patients could be due to subclinical reactivations of HSV and CMV in these patients. Low VZV IgG1 and absence of IgG3 could explain the increased frequency of zoster infections reported in CVI patients. After immunoglobulin substitution, herpesvirus-specific IgG1 titers increased while HSV and CMV IgG3 decreased or remained stationary. In two unsubstituted patients, HSV and CMV titers remained stationary during 1 and 5 years, respectively, while an increase of VZV IgG1 and IgG3 indicated VZV reactivation although the patients remained asymptomatic.

Adult↗

Ontogeny of immunoglobulins in bone marrow-transplanted individuals. An analysis of serum and salivary levels.

Unstimulated whole saliva and serum samples were collected from ten allogeneic bone marrow transplant recipients before and after bone marrow transplantation, seven donors, and from twenty healthy individuals. Two patterns with regard to salivary IgA were found after transplantation. In five patients, a short-lasting peak of excessive IgA production was noted shortly after BMT. Two of these patients had an increase of both secretory and the nonsecretory form of IgA, whereas the other three only demonstrated elevated nonsecretory IgA levels. After the IgA peak the IgA level decreased below the level before BMT. In five patients a different pattern was seen, with a marked decrease in salivary IgA, IgG, and IgM as well as albumin after grafting. A highly variable pattern of reconstitution was seen after one year, when three out of seven patients were still deficient in secretory IgA.

Adolescent↗

Dentin resorption in replanted monkey incisors. Morphology of dentinoclast spreading in vivo.

Dentinoclast colonization of a dentin surface was examined with special reference to changes in plasma membrane morphology during spreading and development into actively resorbing cells. Experimental cavities on the root surfaces of freshly extracted and replanted monkey incisors with infected pulps were examined with scanning electron microscopy after predetermined time intervals. The surface morphology of the dentinoclasts during the different spreading stages, and the fact that the stages appeared in a time-related mode indicated that dentinoclasts follow the general pattern of cell attachment and spreading on solid substrata, with a few exceptions unique to mineralized tissue resorbing cells. As a result, a 3-stage spreading model was proposed. In stage 1, dentinoclasts were characterized by an abundance of filopodia projecting towards the dentin surface. The cells appeared to be exploring the surface to find an area suitable for resorption. This was followed by an increase in cell size accompanied by a progressive disappearance of the peripheral filopod fringe (stage 2). Stage 3 apparently represented the final stage of adaptation and was characterized by an active resorption of the dentin surface.

Animals↗

Evidence for a role of odontogenic epithelium in maintaining the periodontal space.

Explants of enamel organ epithelium or squamous epithelium from the oral cavity were placed in experimental cavities in the root surfaces of extracted and subsequently replanted monkey incisors. Control cavities without explants were also prepared. After an observation period of 8 weeks, histological evaluation of the cavities originally containing odontogenic epithelium showed a reparative cementum layer on the dentine surface and islands of epithelium in the periodontal connective tissue in the experimental cavities. Bone was not found in the cavities and the alveolar bone had been resorbed around the epithelial islands to a distance corresponding to the periodontal space adjacent to the cavities. Control cavities and cavities originally containing squamous epithelium also showed repair with reparative cementum, but the alveolar bone had grown into the cavities not, however, into contact with the dentine surface. These findings indicate a physiological rôle for odontogenic epithelium, in particular the epithelial rests of Malassez in the periodontal membrane for maintaining the width of the periodontal space and preventing dento-alveolar ankylosis.

Animals↗

Influence of pulpal treatments on cell and tissue reactions in the marginal periodontium.

The effects of pulpal infection and intrapulpal application of calcium hydroxide and antibiotics were evaluated with special reference to cell and tissue reactions in the marginal hard/soft tissue interface in monkeys. Results indicate the pulpal conditions and endodontic dressings influence marginal healing and repair, provided an endodontic-periodontic pathway such as patent dentin tubules is present. These results suggest that permanent endodontic treatment, with an inert material, should be performed before the protective cementum layer is removed. Pulpally aggravated periodontal lesions should therefore not be overlooked in periodontal diagnosis and treatment.

Animals↗

Characterization of alkaline phosphatase from buccal mucosa in young rats.

Alkaline phosphatase (APase) is a plasma membrane-integrated protein with unknown function and is found in many different tissues of the body. It is normally not present in squamous epithelium. Nevertheless, it has been demonstrated in developing rat oral epithelium, where it exists together with several different phosphatases. In this study APase was solubilized from rat buccal mucosa and partially purified by gel chromatography followed by ion-exchange chromatography. Three isoenzymes with similar kinetic characteristics but different sensitivities to heat inactivation were obtained. All three had a pH optimum of 10.2 and a Michaelis-Menten constant of 0.3 mM. Combined chromatographic/electrophoretic and histochemical tissue section analysis of APase isoenzymes indicated that the buccal mucosa of young rats contains three APase isoenzymes, two of which are of epithelial origin and the third of endothelial origin.

Alkaline Phosphatase↗

Anti-DNA antibody synthesis after bone marrow transplantation: implications for IgG subclass restrictivity and pathogenicity of autoantibodies.

Two patients developed antinuclear antibodies (ANA) including antibodies directed against double-stranded DNA (dsDNA) after bone marrow transplantation. In one of the patients very high levels of IgM, IgG as well as IgA anti-dsDNA were found during 6 months in the absence of symptoms of systemic lupus erythematosus (SLE). The other patient made IgM anti-dsDNA antibodies for a period of more than 3 years, also in the absence of SLE symptoms. The ANA were restricted to the IgG1 and IgG3 isotypes as is the case in SLE but did not express idiotypes commonly found in this autoimmune disease. The occurrence of these antibodies may reflect a non-antigen induced expansion of the existing donor B-lymphocyte repertoire.

Antibodies, Antinuclear↗