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Biomedical subjects

A Linde

Publications and source records attributed to A Linde.

At least 19 recordsLinked to original sources

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

Virological and clinical characteristics of human herpesvirus 6.

Six distinct human herpesviruses have been identified. They include Herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2), Cytomegalovirus (CMV), Varicella-zoster virus (VZV), Epstein-Barr virus and the recently described Human herpesvirus 6 (HHV-6). With the exception of HSV-2, the members of the family are ubiquitous and infect most of the human population in the first decade of life. HHV-6 possesses morphological and structural features characteristic of members from the herpesvirus family but it is both genetically and immunologically distinct from other members. The virus was first identified in 1986 by the group at the National Institutes of Health, Bethesda. Not until 1988 was the primary disease identified as that of a common childhood disease, exanthema subitum. There are independent reports on isolations of HHV-6 from the USA, Japan, U.K., Australia and Africa, demonstrating that the virus is a widespread agent. Its possible involvement in chronic fatigue disease and as a cofactor of development of AIDS are still subjects for discussion.

Herpesviridae Infections

An enzyme-linked immunosorbent assay for IgG antibodies to human herpes virus 6.

An indirect enzyme-linked immunosorbent assay (ELISA) with human herpes virus 6 (HHV6) membrane antigen was compared with indirect immunofluorescence assay (IFA) for measurement of HHV6 IgG antibodies. Five hundred serum samples from 403 Swedish patients with suspected symptomatic Epstein-Barr virus (EBV) infections were examined. The specificity of the ELISA compared with IFA was 98.7% and the sensitivity was 98.4%. In 90% of the patients, IgG antibodies to HHV6 were detected with both assays. The highest HHV6 IgG titers were found mainly in patients with EBV or CMV infections, but HHV6 mononucleosis was not diagnosed. The same HHV6 antigen was assessed for IgM ELISA but was found to be of limited value due to high IgM reactivity with the control antigen. The HHV6 IgM ELISA requires further investigation. The IgG ELISA described is a reliable alternative to IFA for measurement of HHV6 IgG antibodies and for large scale epidemiological studies.

Antibodies, Viral

Evaluation of enzyme-linked immunosorbent assays with two synthetic peptides of Epstein-Barr virus for diagnosis of infectious mononucleosis.

To diagnose infectious mononucleosis caused by Epstein-Barr virus (EBV), a peptide from the EBV nuclear antigen (EBNA) 1 (p107) and an EBNA 2 peptide (polyproline) were used as antigens in enzyme-linked immunosorbent assays for IgG and IgM. Well-characterized serum samples (360) from healthy individuals and patients with EBV or cytomegalovirus infections were examined. The p107 IgG and IgM assays were also tested with serum from 1000 patients with suspected EBV-related disorders. The p107 and polyproline IgG assays were 100% specific for EBV seropositivity. Low p107 IgG titers (less than 1000) were found in 98% of patients with EBV infectious mononucleosis but also in 18% of patients with other diseases. A p107-to-polyproline IgG ratio of less than 1 was 98% specific for EBV infectious mononucleosis; sensitivity was 86%. In EBV capsid antigen-IgG seropositive patients, a p107 IgG titer of less than 1000 together with a p107 IgG-to-IgM ratio of less than 1 was 98% sensitive and specific for EBV infectious mononucleosis. Thus, this ratio appears adequate to measure EBNA antibodies for diagnosis of EBV mononucleosis.

Antigens, Viral

Aberrant IgG subclass distribution to measles in healthy seropositive individuals, in patients with SSPE and in immunoglobulin-deficient patients.

Sera from healthy seropositive donors, patients with acute measles, subacute sclerosing panencephalitis, common variable immunodeficiency, and CH gene deletions were analysed for anti-measles IgG1-4. Compared with other anti-viral immune responses of IgG1 and IgG3, an unusual predominance of specific IgG1 prevailed; only four out of a total of 68 patients showed anti-measles IgG3. Of the 17 healthy, measles seropositive serum donors, all showed specific IgG1, none showed IgG3 and six had IgG4. Eight out of 10 patients with SSPE showed an anti-measles IgG1 and IgG4 response while IgG3 was not seen. The IgG1 and IgG4 subclass patterns had some exceptions. Anti-measles IgG3 was found in five out of five patients with deletion of the gamma-1 encoding gene segments and in four out of 15 patients with recent measles antigen stimulation. The subclass pattern was suggested to reflect the immunological compromise associated with measles infections.

Adolescent

Specific in vitro IgG subclass synthesis and lymphocyte proliferation responses in herpes virus encephalitis.

Cerebrospinal fluid, peripheral blood lymphocytes (PBL) and sera from 5 patients with herpes simplex encephalitis (HSVE), 3 with varicellae zoster (VZV) meningoencephalitis and 5 with encephalitis of unknown origin (NUD) were analyzed. Lymphocytes from both blood and CSF were shown to synthesize anti-VZV IgG subclasses in VZV meningoencephalitis and anti-HSV IgG subclasses in HSVE. The subclass patterns of CSF and in vitro synthesized anti-viral IgG were similar, suggesting that a considerable portion of the antiviral IgG subclasses detected are synthesized in the CNS compartment. Antigen presentation in vitro seemed to produce a heterologous IgG4 and/or 3 response in 3 patients. Lymphocyte proliferation was detectable in response to HSV and VZV, respectively.

Antibodies, Viral