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Biomedical subjects

A Linde

Publications and source records attributed to A Linde.

At least 181 records · Page 10Linked to original sources

Dentinogenesis.

The formation of dentin, dentinogenesis, comprises a sophisticated interplay between several factors in the tissue, cellular as well as extracellular. Dentin may be regarded as a calcified connective tissue. In this respect, as well as in its mode of formation, it is closely related to bone. Using dentinogenesis as an experimental model to study biomineralization provides several practical advantages, and the results may be extrapolated to understand similar processes in other tissues, primarily bone. After describing dentin structure and composition, this review discusses items such as the morphology of dentinogenesis; the dentinogenically active odontoblast, transport, and concentrations of mineral ions; the constituents of the dentin organic matrix; and the presumed mechanisms involved in mineral formation.

Animals↗

Osteopromotion: a soft-tissue exclusion principle using a membrane for bone healing and bone neogenesis.

The research reviewed in this paper constitutes a series of investigations intended to develop and evaluate a new membrane technique, which provides improved conditions for osteogenesis during healing of bone defects and restitution of earlier existing bone. The technique has also been shown to aid in bone grafting as well as having the capacity to create new bone for reconstructive purposes. According to this methodology, membranes are utilized to create a space in the tissue in which osteogenesis can occur relatively unimpeded. The paper provides a review of our initial animal experimental work as well as some clinical studies with special emphasis on membrane use in conjunction with dental implants. Possible mechanisms behind the efficacy of the membrane technique are reviewed, and future perspectives of development are also discussed. The osteopromotive membrane technique represents a principally new and major advance in bone biology and reconstructive skeletal surgery. Based on the results obtained by us and by others, the technique is presently utilized clinically in some routine applications.

Animals↗

Diagnosis of cytomegalovirus infections using polymerase chain reaction, virus isolation and serology.

The nested Polymerase Chain Reaction (PCR) was compared with virus isolation and serology to establish which is the best method for the diagnosis of active cytomegalovirus, (CMV) infection. Samples of blood leucocytes, urine and throat washings from immunosuppressed patients and patients with congenitally acquired CMV infection, as well as from healthy persons, were examined with PCR. CMV DNA was detected in all samples from which CMV could be isolated, but not from any sample from healthy adults, whether CMV seropositive or CMV seronegative. In contrast to the findings in healthy persons, CMV genomes were frequently detected in urine and throat washings from immunosuppressed, CMV-seropositive patients without symptoms of CMV infection. The appearance of CMV genomes in blood cells in immunosuppressed CMV-seronegative patients may be the first sign of primary CMV infection. Congenital CMV infection could be rapidly and safely diagnosed when urine samples were examined by PCR. Nested PCR is a valuable tool for the diagnosis of active CMV infection, when selected materials are used.

Adolescent↗

Diagnosis of cytomegalovirus in bronchoalveolar lavage by polymerase chain reaction, in comparison with virus isolation and detection of viral antigen.

Bronchoalveolar lavage (BAL) products from 52 immunocompromised patients with symptoms of pulmonary infection was examined for cytomegalovirus (CMV) by virus isolation, polymerase chain reaction (PCR) and detection of CMV antigen by immunofluorescence or immunoperoxidase staining after short-term incubation in tissue culture and directly in BAL cells. We found that PCR detected all cases positive by virus isolation (15/52 samples) and the result was obtained within 5 h. PCR detected more cases of CMV than did virus isolation (22/52 samples). Positive PCR and negative virus isolation were consistent with probable CMV infection in 3/7 patients when other clinical and laboratory parameters of CMV infection were considered. The negative predictive value of PCR was high; none of 30 patients negative by PCR developed CMV pneumonia within the subsequent 2 months. Detection of CMV antigen after short-term incubation was rapid enough to be used in clinical practice, specific (100%) and with a sensitivity of 60%. Demonstration of CMV antigen in alveolar cells was highly specific (100%) but had too low a sensitivity (26.7%) to be used as the only rapid method. Our conclusion is that a combination of PCR and detection of CMV antigen after short-term incubation and directly in alveolar cells is optimal for rapid identification of CMV.

Adolescent↗

Stimulation of early bone formation by the combination of an osteopromotive membrane technique and hyperbaric oxygen.

Large bone defects often heal incompletely as a result of ingrowth of connective tissue. By using a mechanical hindrance, a porous expanded polytetrafluoroethylene (e-PTFE) membrane, it is possible to prevent fibroblasts and other soft connective tissue cells from entering the defect, thereby allowing osteogenesis to occur unhindered. As evidenced in several investigations, this osteopromotive membrane technique causes a strongly improved bone regeneration of well defined osseous lesions. Hyperbaric oxygen treatment has also been shown to accelerate bone healing. In this study the value of combining the two techniques was investigated. Through-and-through bone defects, 5 mm in diameter, were produced unilaterally in the angular region of the mandibles of adult rats (n = 60); the defects in half the number of animals were covered lingually and buccally with membranes. The animals were then divided into four groups: treatment with membrane alone, treatment with hyperbaric oxygen alone, combined treatment, and no treatment. Histological examination of the defects after 14 days showed that the combination of techniques had resulted in significant improvement in bone healing, compared with hyperbaric oxygen or the membrane technique alone. Synergistic effects can thus be achieved by the use of membranes and stimulatory factors for bone regeneration.

Animals↗

A monkey model for Epstein Barr virus-associated lymphomagenesis in human acquired immunodeficiency syndrome.

High-grade malignant nonHodgkin's lymphomas--five lymphoblastic, three pleomorphic, and two immunoblastic--developed in 10/25 cynomolgus monkeys (Macaca fascicularis) followed for up to 746 d after infection with simian immunodeficiency virus, strain SIVsm. These lymphomas were shown to be associated with an Epstein-Barr (EB)-like cynomolgus B-lymphotropic herpesvirus (CBLV) by electron microscopy, by Southern blot hybridization with probes against human EBV, and by the expression of antigens corresponding to EBV-associated nuclear antigens (EBNAs) involved in human B cells transformation. Southern blot demonstration of immunoglobulin gene rearrangements and homogeneous EBV episomes indicated that all the lymphomas were CBLV-associated monoclonal B cell proliferations. Our findings suggest that these tumors correspond to the EBV-associated malignant lymphomas in acquired immunodeficiency syndrome with respect to clinical, morphological, phenotypic, and genotypic characteristics. The particular susceptibility of SIVsm immunodeficient cynomolgus monkeys for CBLV-associated lymphomagenesis appears therefore a useful model for EBV-associated lymphomas in humans.

Animals↗

Immunoglobulin G subclasses and lymphocyte stimulatory responses to cytomegalovirus in transplant patients with primary cytomegalovirus infections.

The early activation of T- and B-cell responses to cytomegalovirus was studied in immunosuppressed patients. Primary lymphocyte stimulation to cytomegalovirus (CMV) antigen, a measure of T-helper activity, and anti-CMV IgG subclass responses were analyzed. Ten patients suffering from primary CMV infection following renal transplantation were studied. Of the ten, nine became positive for CMV induced lymphocyte proliferation 5-40 weeks after transplantation. Nine showed an almost simultaneous appearance of anti-CMV IgG1 and three at 3-32 weeks after transplantation, while one patient synthesized only low levels of anti-CMV IgG1. The lymphocyte proliferation assays have limited diagnostic value for primary CMV infection in renal transplant patients. The humoral and cellular immune responses seemed to be independent of each other.

Adolescent↗

Calcium ion activity and pH in the odontoblast-predentin region: ion-selective microelectrode measurements.

Ca2+ ion activities and pH were measured in the odontoblast/predentin region of rat incisors by means of the microelectrode technique. In Ringer solution, the apparent resting membrane potential of odontoblasts was determined to be -24 +/- 4 mV (mean +/- SE), whereas the odontoblast intracellular pH was found to be 6.66 +/- 0.02. The values obtained are within the range of other cell types, as measured in similar incubating solutions. The pH in the extracellular predentin was higher than the intracellular pH, 7.00 +/- 0.02. The Ca2+ ion activity in predentin (pCa = 2.94 +/- 0.15) was found to be significantly (P less than 0.001) higher than that in the dental pulp extracellular fluid (pCa = 3.37 +/- 0.14). The 2-3 times higher calcium activity extracellularly in predentin, compared with the dental pulp, implies the existence of some ion-concentrating mechanism across the odontoblast layer in the direction of the mineralization front.

Animals↗

Calcium ion transport kinetics during dentinogenesis: effects of disrupting odontoblast cellular transport systems.

Due to strongly discrepant results in the literature, controversy exists about the timing of the transport of Ca2+ ions to the mineralization front during dentinogenesis and the role of the odontoblasts in this transport. The present study gives evidence, by means of autoradiography as well as by a radiochemical technique, that the transport time for Ca2+ ions into the dentin mineral phase is about 10-15 min in the rat incisor. The results also show that technical factors, such as mode of tracer injection and the use of perfusion fixation, may influence the results more or less strongly. Finally, by disturbing odontoblast microtubules, involved in intracellular transport processes, and by blocking odontoblast calcium uptake channels by nifedipine and neomycin, the Ca2+ ion transport into dentin mineral was found to be strongly impaired. This may be taken as an indication that transcellular calcium transport mechanisms have a role during dentinogenesis.

Animals↗

Role of osteopromotion in experimental bone grafting to the skull: a study in adult rats using a membrane technique.

This study explores the effect of an osteopromotive membrane technique in a mature animal model on the survival of membranous and endochondral bone inlays in mandibular defects and membranous bone onlays on the calvarial roof. Twenty-eight adult male rats received fibular or mandibular inlay bone grafts to trephine defects in the mandibular angle, as well as mandibular disc onlay grafts to the parietal and frontal bone regions. The results were assessed by gross inspection and light microscopy after 12 weeks. Membrane use markedly promoted bone deposition in the defects. The membranous bone inlays showed complete incorporation to the margins of the defect, whereas the endochondral grafts at all times were covered by a thin fibrous capsule and failed to incorporate. Onlay grafts generally resorbed substantially, but the grafts covered by a membrane seemed more active, developed an increased cancellous component, and showed less pronounced volumetric loss. The findings confirm the fact that a biological difference exists between membranous and endochondral bone. They also confirm the osteopromotive effect of the membrane technique, and suggest that the amount of bone needed for transplantation can be reduced using this method.

Animals↗

Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome.

The immunopathology in primary Epstein-Barr virus (EBV) infections and in chronic fatigue syndrome was studied by examining serum levels of interleukins (IL) and of soluble T cell receptors in serum samples. Serum samples were from patients during and 6 months after primary EBV-induced infectious mononucleosis and from patients with chronic fatigue syndrome and serologic evidence of EBV reactivation. Markers for T lymphocyte activation (soluble IL-2 and CD8) and for monocyte activation (neopterin) were significantly elevated during acute infectious mononucleosis but not in patients with chronic fatigue syndrome. Interferon-alpha, IL-1 beta, and IL-6 levels were not significantly increased in any patient group but inferferon-gamma levels were significantly increased during the acute phase of infectious mononucleosis. The levels of IL-1 alpha were significantly higher than in controls both in patients with infectious mononucleosis and in those with chronic fatigue syndrome. In the latter, the lack of most markers for lymphocyte activation found in patients with infectious mononucleosis makes it less likely that EBV reactivation causes symptoms.

Adolescent↗

Herpesvirus serology, aberrant specific immunoglobulin G2 and G3 subclass patterns and Gm allotypes in individuals with low levels of IgG3.

One objective of this study was to determine whether IgG3-deficient individuals have an increased frequency of reactivated herpesvirus infections. Serum titres to Epstein-Barr virus (EBV) and human herpesvirus-6 were examined in 10 healthy and in 10 symptomatic persons with serum IgG3 < 0.1 g/l. Atypical titres were found in 16% of the IgG3-deficient individuals. Reactivations of these viruses thus do not seem common in IgG3 deficiency. Antigen-specific IgG responses were also determined. A lowered frequency of IgG3 to an EBV-derived peptide was found only in symptomatic, IgG3-deficient individuals. Levels of IgG2 to a bacterial polysaccharide were lowered in the same group, despite normal serum levels of total IgG2. A functional IgG2 deficiency may contribute to symptoms in IgG3 deficiency. The G3(g) allotype, known to be associated with low total IgG3, dominated in IgG3-deficient persons (13/17) independently of presence or absence of symptoms. A linkage of G3(g) to the G2(n) negative allotype, associated with low IgG2, was equally common irrespective of symptoms. G3(g) and absence of G2(n) seem to be one prerequisite for most of IgG3 deficiency combined with low specific IgG2.

Antibodies, Viral↗

Intrathecal antibody production against viruses of the herpesvirus family in acute retinal necrosis syndrome.

Viruses of the herpesvirus family cause acute retinal necrosis syndrome, a devastating necrotic retinitis in immunocompetent individuals. Direct proof of the viral origin of this disease may be obtained by demonstration of the virus, viral antigens, or viral DNA in biopsy specimens of retinas. In search of alternative diagnostic methods, we analyzed cerebrospinal fluid and serum with enzyme-linked immunosorbent assays for virus-specific antibody activity. Intrathecally produced viral antibodies were found in three consecutive patients with acute retinal necrosis syndrome: herpes simplex type 2 in a 30-year-old woman with a history of suspected neonatal herpes encephalitis, herpes simplex type 1 in a 35-year-old man, and varicella-zoster virus activity in a 62-year-old woman. None of the patients had clinical signs indicating an acute disorder in the central nervous system. This serologic approach seems to be of value for the diagnosis of an associated intracerebral viral infection in cases of acute retinal necrosis syndrome.

Adult↗

Cytomegalovirus DNA detection of an immediate early protein gene with nested primer oligonucleotides.

A rapid and sensitive polymerase chain reaction (PCR) was developed to detect conserved sequences from the immediate early gene of human cytomegalovirus (HCMV). The primers sequences were from EcoRI J fragment of Ad169. The first primer set was selected to amplify a 242 bp fragment and the next primer set was nested within the first and amplified a 146 bp fragment. With the single PCR system it was possible to detect 100 fg HCMV DNA but with double PCR 5-10 fg were detectable. Specific amplification was seen in urines from patients with HCMV infections. 20 urine samples were analysed by single PCR, double PCR and virus cultivation. The double PCR was the most sensitive method. Urines from healthy seropositive persons and cells infected with other members of the herpes virus family were negative with all three methods. This suggests that specific amplification by double PCR is sensitive and can be used for rapid detection of HCMV DNA in cases with activated infection.

Antigens, Viral↗

Acute peripheral facial palsy: CSF findings and etiology.

CSF and serum were examined in acute and convalescence phase from 56 patients with acute idiopathic peripheral facial palsy. CSF protein analysis, viral and borrelia serology were performed. Borrelia infection was found in 9/56 cases and was often associated with inflammatory CSF findings. One patient each had serological evidence for a recent or ongoing infection with herpes simplex, varicella zoster, adeno, influenza B, echo and Epstein-Barr virus, but none had specific intrathecal antibody synthesis; 11 patients had a serological pattern compatible with a reactivated Epstein-Barr virus infection. Eleven patients displayed mononuclear CSF pleocytosis. Four of them had a borrelia infection. A disturbed blood-brain barrier was observed in 19 patients. Intrathecal immunoglobulin synthesis as indicated by elevated IgM-indices was found in 16 patients and by IgG indices in three. Nine patients had oligoclonal IgG bands in serum and CSF, three exclusively in CSF. It is concluded that patients with facial palsy often have inflammatory CSF findings, indicating a generalised central nervous system affection, and not only a mononeuritis. The importance of viral infections in the pathogenesis is still obscure. Borrelia is the most common infectious cause of facial palsy.

Adolescent↗

Osteopromotion for cranioplasty. An experimental study in rats using a membrane technique.

Various techniques for treatment of large cranial defects have been reported, but the use of alloplastic materials still seems to predominate. The authors have applied and explored a new approach for bone repair which appears promising, even for use in less osteogenic environments such as the adult calvaria. Seventy-two adult Sprague-Dawley rats each received bilateral 8-mm trephine defects in the temporoparietal area; this defect size precludes spontaneous osseous healing during the lifetime of the animal. Five surgical procedures, employing various alternatives of biologically inert expanded polytetrafluoroethylene membrane positioning and intramembranous bone-chip implantation, were performed and compared to control defects. Slight improvement of bone regeneration was demonstrated with subperiosteal ectocranial and endocranial membranes, alone or in combination, and with bone chips alone or in combination with an outer or inner membrane. Virtually complete bone healing was observed in animals receiving both an outer and an inner membrane with interpositioned bone chips. The latter appeared to function primarily as space-holders by keeping the membranes separated throughout the defect. Consequently, this technique seems to significantly promote bone repair by excluding soft-tissue components from the bone-healing site.

Animals↗