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Biomedical subjects

A Linde

Publications and source records attributed to A Linde.

At least 145 records · Page 8Linked to original sources
PubMed1995

Recombinant bone morphogenetic protein-2 enhances bone healing, guided by osteopromotive e-PTFE membranes: an experimental study in rats.

It has been shown earlier that it is possible to improve bone healing, to regenerate previously existing bone, and to create new bone by means of an osteopromotive membrane technique. The present study addresses the question of whether it is possible to combine this technique with a locally applied factor, stimulatory to osteogenesis. Circular transosseous 'critical size' defects in mandibles of rats were either implanted with recombinant human bone morphogenetic protein type 2 (rhBMP-2) or were left empty; half the number of implanted and half the number of empty defects were covered with an expanded polytetrafluoroethylene (e-PTFE) membrane (GORE-TEX). Results were evaluated after 12 and 24 days of healing by a histomorphological scoring system. Implantation of rhBMP-2 alone resulted in bony bridging of the defect after only 12 days, but also in voluminous amounts of new bone outside the original defect area. When rhBMP-2 was combined with membrane, newly formed woven bone bridged the defect and the bone contour was maintained by the membrane. The combined treatment with membrane and rhBMP-2 demonstrated a significantly better bone healing than with e-PTFE membrane alone at both 12 days and 24 days of healing. It was concluded that rhBMP-2 has a strong osteoinductive potential and, in contrast to what was found earlier with other types of BMP preparations, this potential was retained when combining the rhBMP-2 with the osteopromotive membrane technique, yielding better bone healing than with the membrane alone, and at the same time maintaining the bone contour.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Morphological alterations in dental and periodontal tissues in murine mucopolysaccharidosis type VII.

Mucopolysaccharidoses (MPSs) in humans are frequently associated with tooth and periodontal aberrations. Although the cause is known, namely, enzyme deficiency, the pathophysiology of these alterations is not well defined. A murine MPS VII (beta-glucuronidase deficiency) model has earlier been identified with morphological, genetic, and biochemical characteristics that closely mimic those of human MPS VII. The present investigation describes the histopathological alterations in dental and periodontal tissues from such mutant mice. Homozygous animals were identified by external phenotypical features and as being beta-glucuronidase deficient by a fluorometric assay of liver samples. In the incisor and the periodontium, abnormalities were evident in both cells and the extracellular matrices. Mesenchyme-derived cells were more aberrant than epithelial cells. Moreover, undifferentiated cells appeared unaffected, whereas actively synthesizing and resorbing cells were distended by virtually empty or granular material-containing vacuoles, the content presumably being glycosaminoglycans. The cells most affected were those in which macromolecular turnover is normally the highest, namely, odontoblasts, postsecretory ameloblasts, and periodontal ligament fibroblasts. Extracellularly, predentin displayed abnormal collagen fibrils, whereas mineralization defects occurred in both dentin and enamel. This murine model of MPS VII provides a good tool for understanding the pathophysiology of this disease in bone, periodontium, and teeth.

Ameloblasts↗
PubMed1995

Healing of mandibular defects with different biodegradable and non-biodegradable membranes: an experimental study in rats.

Membranes, clinically used to improve bone regeneration according to the osteopromotion principle, have primarily been made of expanded polytetrafluoroethylene (Gore-Tex Membrane). Recently, different types of biodegradable membranes have become available. This investigation explored the osteopromotive potential of 10 different biodegradable and non-biodegradable membrane materials. Scanning electron microscopy revealed quite different surface configurations of these membranes, even though some of them were chemically closely related. Standardized, transosseous, critical size mandibular defects were made bilaterally in adult rats and were randomly covered with the different types of membrane. After 6 wk of healing, evaluation was performed by light microscopy according to a histological scoring system. Varying degrees of bone healing were seen beneath the different membranes. Some of the membranes (such as Gore-Tex Augmentation Material, Millipore and Resolut 'long term') revealed a good osteopromotive effect, whereas others had little or no beneficial effects on bone healing. Certain membrane materials caused a pronounced inflammatory response in the surrounding soft tissue, while others displayed a low inflammatory reaction. The study shows that different membranes differ strongly in osteopromotive efficacy, even if seemingly chemically closely related. Furthermore, the study demonstrates that membranes developed primarily for periodontal regeneration purposes may not be adequate to promote bone healing.

Animals↗
PubMed1995

Epstein-Barr virus (EBV) DNA in saliva and EBV serology of HIV-1-infected persons with and without hairy leukoplakia.

Secretion of Epstein-Barr virus (EBV) in saliva, as well as serum antibody titres against various EBV antigens, were analyzed in respect of (1) 15 HIV-1-infected patients with oral hairy leukoplakia proven to contain EBV by in situ hybridization, (2) 45 HIV-1 infected patients without hairy leukoplakia, (3) 10 HIV-1 infected patients treated with acyclovir or foscarnet and (4) 21 healthy controls. The numbers of CD4+ cells in the peripheral blood were also recorded. The HIV-1 infected patients were at various stages of HIV-1-associated disease. Excretion of EBV DNA in the saliva was determined by means of the polymerase chain reaction (PCR) while the amount of EBV DNA in positive samples was estimated by repeated titrations. The frequency of shedding of EBV DNA increased from 33% in healthy controls to 78% in asymptomatic HIV-1 infected persons, but did not increase significantly with progression of HIV-1-associated disease. The titres of EBV DNA in saliva correlated inversely and significantly with the number of CD4+ cells in the peripheral blood. All patients with hairy leukoplakia shed by EBV DNA in their saliva but the titres were not significantly higher than those of other HIV-1 infected persons. The serum titres of antibodies against EBV nuclear antigen 1 (EBNA-1) correlated positively and significantly with the CD4+ cell count in the peripheral blood. EBNA-1 IgG antibody in the serum was also significantly lower in symptomatic than in asymptomatic HIV-1 infected persons. There were, however, no significant differences in serum antibodies to various EBV antigens between patients with and without hairy leukoplakia.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Experience with e-PTFE membrane application to bone grafting of cleft maxilla.

Previous clinical studies and animal experiments have demonstrated that the placement of expanded polytetrafluoroethylene (e-PTFE) membranes (GORE-TEX) may be valuable for bone regeneration in nonosteogenic areas. This study aimed to explore the application of this technique to bone grafting of wide alveolopalatal clefts. Ten patients with bilateral clefts were selected and during a 2-week period, all received autogenic cancellous iliac bone bilaterally. The membrane was placed nasally and orally on the larger cleft side and removed after 3-6 months. All patients have been followed for 14 months. Bone graft incorporation was successful except for one patient (membrane side), who was regrafted 1 year later. However, soft-tissue problems with membrane exposure occurred in the majority of patients, while on the nonmembrane side, healing was uneventful in all cases. Further research in membrane technology is necessary before this method can be accepted for cleft grafting.

Adolescent↗
PubMed1995

A role for a new herpes virus (KSHV) in different forms of Kaposi's sarcoma.

Kaposi's sarcoma (KS) is a previously rare, tumour-like lesion of controversial biological nature. KS has since the early 1980s become frequent in patients with AIDS, particularly in homosexuals. KS is also endemic in Central Africa predominantly in otherwise healthy men but also in women and children. Recently, evidence for the presence of novel, herpes virus DNA sequences in more than 90% of AIDS Kaposi lesions (AKS) was presented. This DNA was identified using representational difference analysis (RDA) generating short, unique sequences with variable homology to several herpes virus, but no intact virus was recovered. If these DNA-sequences are also present in other, non-HIV-associated forms of Kaposi's sarcoma this would strongly suggest a specific, aetiopathological involvement of this putative new herpes virus in the pathogenesis of Kaposi's sarcoma, rather than a contamination of yet another opportunistic virus in immunosuppressed AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Ganciclovir therapy for cytomegalovirus (CMV) infection of the central nervous system in AIDS patients: monitoring by CMV DNA detection in cerebrospinal fluid.

Seven AIDS patients with central nervous system (CNS) disease and cytomegalovirus (CMV) DNA in cerebrospinal fluid (CSF) were evaluated before and 3 weeks after standard ganciclovir treatment by nested polymerase chain reaction (PCR) on limiting dilutions and by quantitative PCR. After therapy, PCR CSF was negative for CMV in 3 patients with low baseline levels of CMV DNA and positive with decreased DNA titers in 4 patients with higher baseline levels. CMV pp65 antigen in polymorphonuclear leukocytes was found in 6 of 7 patients before therapy and in none of 5 after therapy. At autopsy, CMV was found in the CNS of the 4 cases examined, including 3 whose CSF was continuously positive by PCR. Quantitative PCR of CSF is useful for monitoring ganciclovir treatment in CMV infection of the CNS. In AIDS patients, standard ganciclovir treatment seems effective in reducing but not suppressing viral replication in severe cases of CMV infection of the CNS.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Localization of S-adenosylmethionine decarboxylase in murine tissues by immunohistochemistry.

S-adenosylmethionine decarboxylase (AdoMetDC), one of three key enzymes in polyamine biosynthesis, is present in minute concentrations in adult tissues, whereas increased AdoMetDC activity occurs in conjunction with differentiation and growth. The occurrence of AdoMetDC in tissues has earlier been studied by biochemical technique only. In this work, an antiserum against recombinant human AdoMetDC was used to investigate the localization of the enzyme in different mouse tissues. In all tissues studied, immunolabeling was seen in cytoplasm, while cell nuclei were negative. In the kidney, AdoMetDC immunoreactivity was confined to the inner part of the cortex; the outer part of the cortex and the medulla displayed only a weak AdoMetDC immunoreaction. In the cortex, renal tubules were strongly reactive, while renal corpuscules were weakly immunolabeled. In developing teeth, AdoMetDC immunoreactivity displayed a gradient of distribution, the immunolabeling intensity being increased from the cervical region to the tip of the cusps. In the incisor, post-secretory ameloblasts were strongly labeled. In the oral mucosa, epithelial cells demonstrated stronger immunolabeling than did cells of the subjacent connective tissue. As for muscle cells, immunoreactive material was confined to the periphery of the fibers. In vitro, treatment with DL-alpha-difluoromethylornithine (DFMO) or methylglyoxal bis-(guanylhydrazone) (MGBG) led to an increase in AdoMetDC. It can be concluded that antibodies to recombinant human AdoMetDC provide a tool for the immunohistochemical localization of AdoMetDC, and that the distribution of the enzyme in the tissues studied gives further support to the importance of polyamines in the development and functions of these organs.

Adenosylmethionine Decarboxylase↗
PubMed1995

Efficacy of bone morphogenetic protein (BMP) with osteopromotive membranes--an experimental study in rat mandibular defects.

The effect of bone morphogenetic protein (BMP) on healing of standardized bone defects was studied with and without the placement of osteopromotive membranes. Two different bovine BMP (bBMP) preparations were tested. These contained primarily collagen as a carrier. Standardized transosseous bone defects, 5 mm in diameter, were created in mandibles of rats. If left untreated, such "critical size defects" never heal during the lifetime of the animal, whereas covering with an osteopromotive membrane is known to cause complete healing of the defects in 6 weeks. The bBMP was implanted in defects and were either covered with an expanded polytetrafluoroethylene (e-PTFE) membrane (GORE-TEX) or were left uncovered. Control defects did not receive any bBMP and were either covered with membrane or were left uncovered. Histological evaluation was made after 12 d and 24 d of healing, respectively. Implantation of bBMP alone was associated with formation of voluminous amounts of new bone, resulting in essentially complete defect healing at 24 d. However, the combination of membrane and bBMP was clearly less effective in stimulating bone healing, being only about as efficient as when using membranes alone. It was concluded that whereas both bBMP preparations were strongly osteoinductive, no further improvement of bone healing was when the membrane technique was supplemented with bBMP, compared to membrane alone. An explanation may be that the presence of an e-PTFE membrane prevents the degradation of the carrier material in the preparations, thus strongly reducing the availability of bBMP.

Animals↗
PubMed1995

Upregulated local cytokine production in recurrent tonsillitis compared with tonsillar hypertrophy.

In children with recurrent tonsillitis there may be persistent antigen deposition in tonsil tissue. even between exacerbations. If so, upregulation of immunocompetent cells should occur continuously, in contrast to tonsil tissue from children with tonsillar hypertrophy. The cytokine pattern was studied in cell suspensions prepared from tonsils obtained from 12 children undergoing tonsillectomy. The study group comprised 6 children with recurrent tonsillitis and 6 who had a history of tonsillar hypertrophy causing sleep apnea. Cytokine-producing cells (IL-1alpha, IL-1beta, TNFalpha, IL-6, IL-8, IL-2, IFNgamma, TNFbeta, IL-10 and IL-4) were characterized at the single-cell level by use of cytokine-specific monoclonal antibodies and indirect immunofluorescence technique. A constitutive production of IL-1alpha, IL-1beta, TNFalpha, and IL-8 was found in both groups (10-300/10(5) cells). However, the frequency of spontaneous IL-2, IFNgamma, TNFalpha, IL-6 and IL-10 was consistently low (10 +/- 10 cells) in both groups. Following restimulation by T-cell receptor ligation, using immobilized anti-CD3 mAb, with concentrations chosen so that it did not activate resting cells, increased frequencies of TNFalpha, IL-6, IL-8, IL-2, IFNgamma, IL-4 and 1L-10 synthesizing cells were induced in the recurrent tonsillitis group. Significantly higher incidences of IL-1beta, IL-6 and IL-2 producing cells were found in the recurrent tonsillitis group (60-200/10(5) cells, p <0.05). Microbiological evaluation in the tonsil tissue could not reveal tiny differences between the studied groups regarding bacterial or viral pathogens. However, this does not exclude persistent increased intracellular deposition of microbial antigens as a possible explanation for the elevated incidence of IL-1beta, TNF-alpha, IL-6, IL-8, IL-2, IFNgamma, IL-10 and IL-4 expressing cells noticed in patients with recurrent tonsillitis.

Cells, Cultured↗
PubMed1995

Dentin mineralization and the role of odontoblasts in calcium transport.

Dentin is formed by two simultaneous processes, in which the odontoblasts are instrumental--the formation of the collagenous matrix, and mineral crystal formation in this matrix. This pattern of formation is similar to that of bone, another mineralized connective tissue. Dentin and bone also have chemical compositions which are similar but with distinct differences. It is of fundamental importance to understand how the ions constituting the inorganic phase are transported from the circulation to the site of mineral formation and how this transport is regulated. For dentinogenesis, calcium is essentially the only ion for which data are available. Recent evidence suggests that a major portion of the Ca2+ ions are transported by a transcellular route, thus being under cellular control. The cells maintain a delicate Ca2+ ion balance by the concerted action of transmembraneous transport mechanisms, including Ca-ATPase, Na+/Ca2+ exchangers and calcium channels, and of intracellular Ca(2+)-binding proteins. The net effect of this is a maintenance of a submicromolar intracellular Ca2+ activity, and an extracellular accumulation of Ca2+ ions in predentin, at the mineralization front. Predentin can be regarded as a zone of formation and maturation of the scaffolding collagen web of the dentin organic matrix. In addition to collagen, it contains little but proteoglycan. Simultaneous with mineral formation, additional non-collagenous macromolecules are added to the extracellular matrix of dentin, these presumably being transported within the odontoblast process. Among these are highly phosphorylated dentin phosphoprotein (phosphophoryn) and another pool of proteoglycan.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1995

From serum to the mineral phase. The role of the odontoblast in calcium transport and mineral formation.

Dentin may be considered as a calcified connective tissue and is in its composition as well as in its mode of formation closely related to bone. Dentin is formed by two simultaneous processes in which the odontoblasts are instrumental: the formation of the proteinaceous dentin matrix, and mineral crystal formation in this matrix. As part of this, the odontoblasts actively transport Ca2+ ions towards the site of mineral formation. The cells maintain a delicate intracellular Ca2+ ion balance by the concerted action of transmembraneous transport mechanisms, including Ca-ATPase, Na+/Ca2+ exchangers and calcium channels of the L-type, and possibly intracellular Ca(2+)-binding proteins. The net effect of this is a maintenance of a cytoplasmic sub-micromolar Ca2+ activity and an extracellular accumulation of Ca2+ ions at the mineralization front. In addition to the major matrix constituent, collagen, non-collagenous macromolecules, such as dentin phosphoprotein (phosphophoryn), dentin sialoprotein, and proteoglycan, are synthesized by the odontoblasts and deposited in the matrix. Such polyanionic macromolecules are presumably responsible for the extracellular induction of hydroxyapatite crystals, but may also function to inhibit mineral growth and to regulate crystal size. Accordingly, it can be concluded that dentinogenesis comprises an interplay between several factors in the tissue, cellular as well as extracellular.

Animals↗
PubMed1995

Polyamine depletion-mediated effects on murine odontogenesis are dependent on tooth developmental stage and culture conditions.

Polyamines are known to play a central role in processes such as growth and development. Virtually nothing is known about their importance in tooth development, an attractive and frequently used experimental model for studies of developmental processes. A polyamine-depleted state was created in tooth cells in an organ culture system. First lower molar germs from 16-and 17.5-day old mouse fetuses were used. alpha-difluoromethylornithine (DFMO) and methylglyoxal bis-(guanylhydrazone) (MGBG) were used to deplete the cells from their polyamine content. Polyamine interconversion and catabolism were prevented by aminoguanidine sulfate (AG). In day-16 germs cultured in serum-containing medium, DFMO reduced the frequency of cycling cells as shown by [3H]thymidine incorporation, and induced a delay of odontoblast differentiation of about 24 h. Under the same conditions, MGBG induced an arrest of histo-morphogenesis, correlated to a significant decrease in the rate of cell proliferation. Addition of polyamines prevented DFMO- and MGBG-induced delay of tooth differentiation. Interestingly, MGBG did not delay the terminal differentiation of odontoblasts and ameloblasts in cultured day-17.5 molars; in these, cells at the tip of the cusps are only a few hours before their withdrawal from the cell cycle. In serum-deprived medium, dental cytodifferentiations did not occur. Addition of putrescine or spermidine to serum-free media, however, allowed for tooth morphogenesis and cytodifferentiation. Tooth explants in a serum-deprived medium reacted to DFMO in a cytocidal fashion, whereas MGBG showed only a mild toxicity in some cell types. Addition of putrescine to DFMO-containing medium prevented its cytotoxic effect. Addition of spermidine to MGBG-containing medium not only prevented its mild toxicity but also allowed for predentin secretion by differentiated odontoblasts. The results are discussed with regard to the well-established developmental events of tooth germs cultured in vitro and with respect to present knowledge of polyamine metabolism and their involvement in cellular processes.

Animals↗
PubMed1995

Diagnosis of cytomegalovirus infection of the nervous system in AIDS by polymerase chain reaction analysis of cerebrospinal fluid.

To evaluate the diagnostic relevance and the clinical impact of the cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for cytomegalovirus (CMV) DNA in the diagnosis of CMV infection of the central nervous system (CNS), 220 acquired immune deficiency syndrome (AIDS) patients with neurological disease were examined. CSF was drawn 1-180 days before death, concomitantly with clinical neurological disease, and autopsy was performed in all the cases. CMV DNA was detected in the CSF from 36 of 45 patients (82%) with CMV infection of the CNS, and in 2 of 175 without CMV infection of the CNS at autopsy. The sensitivity of the method was 82%, the specificity 99%, the positive predictive value 95%, and the negative predictive value 96%. An extensive CMV ventriculitis or encephalitis was shown by histopathology in the majority of the CSF PCR-positive patients with overt clinical encephalitis. Minor CMV lesions only, not likely to cause relevant clinical symptoms, were observed in some CSF PCR-positive patients, concomitant with other opportunistic CNS diseases. CSF PCR is a reliable means for diagnosis of CMV infection of the CNS in patients with AIDS. A positive PCR result, however, requires careful interpretation in the individual clinical context.

AIDS Dementia Complex↗
PubMed1995

Specific T and B cell immunity to measles after allogeneic and autologous bone marrow transplantation.

Lymphocyte stimulation with measles virus antigen (MLY) and ELISA for measles IgG antibodies were performed on 60 patients after allogeneic bone marrow transplantation (BMT), and on 59 patients after autologous bone marrow transplantation (ABMT). The T cell response was significantly higher in the 75 measles seropositive patients than in the 29 seronegative patients (P < 0.001), but not significantly different from the MLY in the 15 patients with uncertain serologic reactivity. When the patient group was divided according to type of transplant, the T cell response to measles was also significantly higher in seropositive patients than in seronegative patients after both ABMT (P < 0.001) and after BMT (P < 0.05). Twenty-three seronegative children who were measles vaccinated after BMT had a significantly higher T cell response to measles (7100 c.p.m.) than 17 seronegative non-vaccinated children (100 c.p.m.; P < 0.01). No significant difference was seen in the T cell response in 12 seronegative children vaccinated after ABMT (2500 c.p.m.) compared to seven children not vaccinated (2800 c.p.m.; NS). Seroconversion after vaccination was more frequent in children after BMT (20/23; 87%) compared to ABMT (5/12; 42%; P < 0.05) but no significant difference was found in the T cell response. Therefore, most patients who lost IgG antibodies to measles after bone marrow transplantation also lost their T cell response to measles. A T cell response to measles developed in most patients who seroconverted after vaccination. Failure to develop antibodies to measles in ABMT patients after revaccination may depend on a persisting T cell immunity.

Adult↗